PMID- 3084108 TI - [Use of bladder biopsy in the study of urinary schistosomiasis]. AB - It is common to find Schistosoma eggs in urine, faeces, and biopsies from rectal mucus membranes presently in use. It is less common to observe adults in routine bladder biopsies. The authors report such a case and discuss the importance of the bladder biopsy to estimate tissular inflammatory response which could reflect the host-parasite balance. PMID- 3084109 TI - Activation of 2',5'-oligoadenylate synthetase and B-2 microglobulin in cancer patients treated with partially pure gamma interferon: dependence of biological effect on administration route. AB - Partially pure immune (gamma) interferon (IFN-gamma) was administered to patients intramuscularly (IM), by rapid IV bolus, and by 6-h continuous infusion as part of a phase I clinical trial. The activity of 2',5'-oligoadenylate synthetase (2,5 A) in peripheral blood cells and the concentration of beta-2 microglobulin (B-2M) in serum were monitored as indicators of interferon biological activity in vivo. Five patients received IFN-gamma by the IM route in doses ranging from 6.5 X 10(5) to 9.6 X 10(6) antiviral units daily. There was little induction either of serum B-2M or of 2,5A in peripheral blood cells. Eight patients received IFN gamma by rapid (5 min) IV bolus infusion in doses ranging from 6.5 X 10(5) to 54 X 10(6) antiviral units daily. As with IM administration, there was little significant induction of 2,5A synthetase, but the concentration of B-2M was increased above pretherapy values in most patients. Eleven patients received IFN gamma by 6-h infusion daily for 10 days at a dosage of 27 X 10(6) units/day. In contrast to IM and IV bolus administration, 6-h infusion of IFN-gamma resulted in significant induction of both B-2M serum concentration and of 2,5A activity in all patients. The induction of 2,5A was highest on days 2 and 4 of therapy and decreased to pretherapy values by day 7. During the second 10-day course of the infusion study 2,5A activity was not induced until day 7 of therapy, and it decreased rapidly thereafter. These studies show clearly that consistent biological activity such as B-2M activation and specific intracellular biochemical events such as 2,5A induction may be optimally obtained by the administration of IFN-gamma by continuous IV infusion. PMID- 3084110 TI - Effects of DFMO-induced polyamine depletion on human tumor cell sensitivity to antineoplastic DNA-crosslinking drugs. AB - We investigated the effect of pretreatment with difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, on the cytocidal responses of four human adenocarcinoma cell lines to two alkylating and crosslinking agents: chlorambucil and N,N',N"-triethylenethiophosphoramide (thiotepa). The cell lines studied included HuTu-80 (duodenum), HT-29 (colon), ME-180 (cervix), and A-427 (lung). A 48- to 72-h pretreatment with DFMO reduced intracellular putrescine and spermidine contents to less than 10% and less than 1% of control levels. This treatment also caused a 30%-70% decline in spermine content. Survival of control and DFMO-pretreated cells after treatment with chlorambucil or thiotepa was measured by a plating efficiency assay. For three of the four lines studied, the DFMO-induced partial polyamine depletion significantly protected cells from the lethal effects of chlorambucil. In ME-180 cultures alone, DFMO pretreatment did not alter the cytocidal efficacy of chlorambucil. Addition of exogenous putrescine to cultures of HuTu-80, HT-29, or A-427 24 h after DFMO addition but 24 h before treatment with chlorambucil reversed the polyamine depletion and its protective effects on chlorambucil-induced cell kill. In contrast to the above observations, DFMO and partial polyamine depletion had no effect on cell survival after thiotepa treatment for any of the cell lines investigated. PMID- 3084111 TI - Growth and development in the haemopoietic system: the role of lymphokines and their possible therapeutic potential in disease and malignancy. AB - Some cells can produce soluble factors which modify the behaviour and/or growth pattern of other cells. These 'factors' are broadly referred to as cytokines and may be further classified on the basis of the cells which were first characterized as the producer cells. For example, lymphokines are the soluble products of lymphocytes and monokines are the soluble factors released by mononuclear phagocytes. Although useful, this nomenclature is in many respects misleading since protein sequence and gene structure analysis has shown that 'lymphokines' may not only be produced by lymphocytes, but by various other types of cells as well. Fortunately, with the advent of molecular techniques, the number of cytokines has decreased drastically and what was once an increasingly large number of factors is now becoming restricted to a manageable few. What remain, however, still pose conceptual and mechanistic problems. These have mainly arisen as a result of the assay systems used to detect and define the lymphokines and the problems in extending the findings to normal physiology. Almost exclusively, lymphocytes have been stimulated to produce and export their soluble factors in response to nonphysiologic stimuli, such as lectins, and the various lymphokines have been characterized on the basis of in vitro test systems. Therefore, for reasons which will become obvious later, many of the in vitro findings have been difficult to corroborate in in vivo situations. Nonetheless, the results obtained with these factors are sufficiently intriguing to warrant serious consideration regarding their relevance in normal haemopoiesis, their possible therapeutic potential and their involvement in disease. PMID- 3084112 TI - Mechanism of phorbol ester activation of calcium-activated, phospholipid dependent protein kinase. AB - Tumor-promoting phorbol esters activated a calcium-activated, phospholipid dependent protein kinase by direct complexation with this protein kinase and phospholipid in the presence of divalent cations and this complexation was identical to association of kinase/receptor activity with cell membranes. Treatment of isolated mouse spleen lymphocytes with phorbol ester tumor promoters resulted in a rapid shift in the subcellular localization of both the phorbol ester receptor and a calcium-activated, phospholipid-dependent protein kinase activity. Both activities shifted from almost entirely soluble to largely membrane-associated, which is consistent with a single protein possessing both activities. Activation of partially purified kinase/receptor activity by phorbol ester or calcium alone or in combination occurred in parallel to the formation of a complex between the kinase/receptor and phospholipid. Magnesium also was important both for complex formation and for activation of the protein kinase. Although phorbol ester did not appear to affect the affinity of the kinase/receptor for phospholipid, it did increase the extent of formation of a stable complex between the receptor and the phospholipid. These observations support the hypothesis that the cell membrane is the locus of action of both the phorbol esters and the calcium-activated, phospholipid-dependent protein kinase activity. PMID- 3084113 TI - Comparative DNA binding of 7,12-dimethylbenz[a]anthracene and some of its metabolites in mouse epidermis in vivo as revealed by the 32P-postlabeling technique. AB - The binding of some mouse skin metabolites and related derivatives of the tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA) was investigated by 32P postlabeling analysis after its topical administration. DMBA and trans-3,4 dihydro-3,4-dihydroxy-DMBA (DMBA-3,4-dihydrodiol) both led to the formation of four DNA adducts, which showed a very similar pattern of spots on thin-layer chromatograms. With trans-8,9-dihydro-8,9-dihydroxy-7,12 dimethylbenz[a]anthracene (DMBA-8,9-dihydrodiol) one major adduct was obtained which was chromatographically indistinguishable from one of the DMBA adducts. In contrast, 7-hydroxymethyl-12-methylbenz[a]anthracene (7-OHM-12-MBA) gave rise to two major adducts which were separable from DMBA adducts. 3-hydroxy-7,12 dimethylbenz[a]anthracene (3-OH-DMBA) and 7,12-dimethylbenz[a]anthracene-7,12 epoxide (DMBA-O2) did not lead to detectable amounts of adducts. Quantitative determination of DNA binding showed that an initiating dose (i = 100 nmol) of DMBA yielded approximately 12 adducts/10(7) normal nucleotides. Adduct formation with the same dose of DMBA-3,4-dihydrodiol was 7-8 times higher. At a 4-fold higher dose level, DMBA-8,9-dihydrodiol exhibited a 3- to 6-times weaker binding and 7-OHM-12-MBA a slightly stronger binding than DMBA. Chromatography of the DMBA and DMBA-3,4-dihydrodiol adducts with a solvent containing borate showed a decreased mobility of two out of four adducts in each case. These adducts were also sensitive to oxidation by periodate. The results suggest that two DMBA adducts carried vicinal cis-hydroxyl groups and thus were probably derived from the anti-3,4-dihydrodiol-1,2-oxide(s) of DMBA. The other two adducts were probably derived from the syn-stereoisomer(s). When the DNA-modifying capabilities and initiating activities of the more prominent mouse-skin metabolites are considered in relation to DMBA, DMBA-3,4-dihydrodiol is postulated to be a proximate and DMBA-3,4-dihydrodiol-1,2-oxide(s) to be ultimate initiators. PMID- 3084114 TI - Inhibition of experimental oral carcinogenesis by topical beta carotene. AB - beta-Carotene was found to significantly inhibit the formation of 7,12 dimethylbenz[a]anthracene (DMBA)-induced squamous cell carcinoma of hamster buccal pouch when applied topically on days alternate to the application of 0.25% DMBA in heavy mineral oil thrice weekly for 22 weeks. An initial experiment utilized 40 male young adult Syrian hamsters divided into four equal groups. Group 1 had DMBA applied to left buccal pouches thrice weekly. Group 2 had DMBA applied as in group 1 but also beta-carotene thrice weekly on days alternate to the DMBA application. Group 3 animals were painted with only beta-carotene and group 4 animals were untreated controls. In a second experiment with 80 animals, beta-carotene was found to inhibit oral carcinogenesis in an initiation- promotion hamster buccal pouch system using 0.1% DMBA as initiator and 40% benzoyl peroxide as promoter. beta-Carotene inhibited both initiation and promotion. PMID- 3084115 TI - Enhancement of collagen-degrading enzymes in the dermis after one topical application of tumor-promoting phorbol esters. AB - The effect of tumor-promoting and non-promoting skin mitogens on the induction of matrix degradation in the dermis of mouse skin has been examined. A stimulation of active collagenolytic and proteolytic enzyme levels was observed after application of the tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 12-O-retinoylphorbol-13-acetate (RPA) as well as the non-promoting skin irritant Ca-ionophore A 23187, but not with the non-irritant mitogen 4-O-methyl TPA. It therefore appears that the enhancement of collagenolytic and proteolytic enzymes after tumor promoter treatment is mainly due to the inflammation that is always caused by the promoter. However, a subfraction of collagenolytic enzymes that is not extracted from the dermis with 0.5 M NaCl but only with 5 M urea is specifically increased after treatment with TPA and RPA. This fraction is absent in A 23187- or 4-O-methyl-TPA-treated dermis. This indicates that apart from inflammation-induced matrix degradation there is also stimulation of enzymes which are directly related to tumor promotion. PMID- 3084116 TI - Specific BPDE I modification of replicating and parental DNA from early S phase human foreskin fibroblasts. AB - Replicating DNA was modified by BPDE I to a greater extent than parental DNA when human fibroblast cells were treated with the carcinogen for 30 min in early S phase. Synchronized cells were exposed to 5-bromodeoxyuridine and treated with non-radioactive BPDE I and [methyl-3H]thymidine in early S phase. The density- and tritium-labeled, replicated DNA was separated from parental DNA in a CsCl gradient. The individual carcinogen-DNA adduct levels in both samples were quantitated by using the 32P-postlabeling method. The total modification of replicated DNA was 1.4-2.4 times greater than parental DNA. This difference was mainly reflected by differences in the main adducts, identified as the 3', [5' 32P]bisphosphates of 7R and 7S-BPDE I-dG. Confirmation of the identity of these two specific carcinogen-DNA adducts was accomplished by co-chromatography on t.l.c. with 3H-labeled 3',5'-bisphosphate adducts. The two 3H- and 32P-labeled adducts were isolated and dephosphorylated. The resultant 3H-labeled deoxyribonucleoside adducts were analyzed on h.p.l.c. and identified by co chromatography with authentic standards. These results suggest that preferential modification of replicating DNA occurs when human cells are treated with BPDE I in early S phase. The ultimate result of this specific modification is the expression of a transformed phenotype. PMID- 3084117 TI - Inhibition of the metabolism of N-nitrosoacetoxymethylmethylamine in the rat by disulfiram. AB - The stability of N-nitrosoacetoxymethylmethylamine (NAMM) in rat serum in vitro, the half-life in blood in vivo and the exhalation rate of 14CO2 after the application of 14C-labelled NAMM were studied with and without disulfiram (DSF) pre-treatment. It was found that the metabolism of NAMM is inhibited by DSF in vitro as well as in vivo. The influence is thought to be due to inhibition of esterase activity, as shown by comparing the kinetics of the degradation of NAMM with those of p-nitrophenylacetate. In contrast to this result the exhalation of 14CO2 does not seem to be influenced by the esterase inhibiting effect of DSF. PMID- 3084118 TI - Three-stage tumorigenesis in mouse skin: DNA synthesis as a prerequisite for the conversion stage induced by TPA prior to initiation. AB - Recent evidence shows that stage I of tumor promotion in NMRI-mouse skin induced by a single dose of 12-O-tetradecanoylphorbol-13-acetate (TPA) can be effected not only after initiation by 7,12-dimethylbenz[a]anthracene (DMBA) but also several weeks prior to initiation. In view of this partial inversion of the initiation-promotion sequence we proposed to replace the term 'stage I of promotion' by the term 'conversion'. The convertogenic effectivity of a single dose of TPA applied after DMBA can be suppressed in a rather characteristic and non-toxic fashion by hydroxyurea (HU). In the present study we asked whether HU might also interfere with the converting effectivity of a single dose of TPA given prior to DMBA. NMRI mice received a single dose of TPA 3 weeks prior to initiation by DMBA which was followed by twice weekly application of skin irritant 12-O-retinoylphorbol-13-acetate (RPA) in order to effect stage II of promotion. A single dose of HU given i.p. at different times after TPA was found to interfere with tumor formation exhibiting an almost complete inhibition if administered 18 h after TPA. This inhibition did not prevent a subsequent promotion by repetitive TPA treatment. The data indicate that conversion can be inhibited by HU in the same characteristic fashion regardless of whether TPA was administered after or prior to initiation. The data also support the autonomous character of the conversion process for which epidermal DNA synthesis appears to be obligatory. PMID- 3084119 TI - In situ characterisation of the oral mucosal inflammatory cell response of rats induced by 4-nitroquinoline-N-oxide. AB - The inflammatory infiltrate induced in palatal and lingual mucosae of Sprague Dawley rats after treatment with the water-soluble carcinogen 4-nitroquinoline-N oxide (4NQO) was investigated using immunohistochemical methods on acetone-fixed frozen sections. Tissues from untreated and solvent-painted control rats were similar to each other and contained small numbers of OX-19+ T cells and larger numbers of W3/25+, LCA+, OX-19- cells within the lamina propria. This latter population could be divided into Ia+ and Ia- subpopulations. Although mucosal specimens from carcinogen-treated rats showed significantly increased numbers of T lymphocytes cells expressing the Ia+ and Ia-, W3/25+, LCA+, OX-19- antigenic phenotypes formed the two predominant cell populations beneath treated epithelium and surrounding tumour islands. Ia+ cells were often detected as focal collections adjacent to or within overlying epithelium which itself appeared to express Ia. None of the tumours showed this focal Ia+ cell infiltrate or expressed Ia. The infiltrates did not contain significant numbers of cytotoxic T cells (OX-8+ and OX-19+) or NK cells (OX-8+, OX-19[-], large granular lymphocytes) and, except for increased cell numbers, the populations present appeared similar to those found in normal mucosa. These results indicate that although immune reactions are stimulated by 4NQO treatment the effector cells necessary for controlling tumour development and growth are absent, perhaps reflecting a passive or stimulatory role in this experimental carcinogenesis model. PMID- 3084120 TI - The effect of macrophage development on the release of reactive oxygen intermediates and lipid oxidation products, and their ability to induce oxidative DNA damage in mammalian cells. AB - Inflammation and the release of potentially damaging substances, such as reactive oxygen intermediates (ROI) and lipid oxidation products from inflammatory cells, have been linked to the potentiation of carcinogenesis. Murine macrophages when stimulated with phorbol esters induce 5,6 ring saturated thymine residues (T'), a lesion of known oxidative origin, in co-cultivated mammalian cells. Induction of this damage was inhibited by catalase and induced in target cells by reagent H2O2 alone. In the present studies, we used defined populations of macrophages with high, low and intermediate capacities for the release of H2O2 or metabolites of arachidonic acid (AA) to assess the relative contribution of these classes of compounds to the induction of saturated thymines. Macrophages activated with Bacillus Calmette-Guerin (BCG), which have the highest capacity for the release of H2O2 and the lowest for the release of metabolites of AA, induced the lowest levels of saturated thymines. Resident macrophages from the unmanipulated peritoneum, which have the lowest capacity for the production of H2O2 and the highest capacity for release of AA metabolites, induced more saturated thymines than did the BCG macrophages. Inflammatory macrophages elicited by casein, which have an intermediate capacity for release of H2O2 and AA metabolites, induced the highest level of saturated thymines. Zymosan, which induced more release of AA metabolites than release of H2O2, was a better stimulant for the induction of T' than TPA, which is a better stimulant for secretion of H2O2. Nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase and cyclooxygenase pathways for metabolism of AA, inhibited the induction of T' by resident macrophages. Indomethacin, an inhibitor of the cyclo-oxygenase path, enhanced induction of T'. Taken together, the data suggest that while H2O2 has the capacity to induce T' in 3T3 cells, it may not be the only mediator of DNA damage and that lipoxygenase generated metabolites of AA may (alone or in concert with ROI) play an important role in the induction of oxidative DNA damage by macrophages. PMID- 3084121 TI - Effect of tamoxifen and D,L-2-difluoromethylornithine on the growth, ornithine decarboxylase activity and polyamine content of mammary carcinomas induced by 1 methyl-1-nitrosourea. AB - The effect of combined treatment with D,L-2-difluoromethylornithine (DFMO) and tamoxifen on the growth status, ornithine decarboxylase (ODC) activity and polyamine content of established 1-methyl-1-nitrosourea (MNU)-induced mammary tumors was investigated. DFMO treatment, a 0.125% solution provided as drinking water, inhibited the rate of tumor occurrence and reduced the number of mammary tumors induced by a high dose of MNU (50 mg/kg body weight) during the first 120 days post-carcinogen treatment. Tamoxifen was administered daily via s.c. injection (25 micrograms/100 g body weight) to tumor-bearing rats in both treatment groups, i.e. control and DFMO-treated, for a 30-day period beginning 120 days after carcinogen. Tamoxifen treatment induced tumor regression but the percentage of regressing, static or growing tumors was no different in the presence or absence of DFMO. Whereas the mammary tumors of DFMO-treated rats had reduced ODC activity and lower polyamine concentrations in comparison to the tumors of untreated animals, tamoxifen had no effect on these parameters independent of its effect on tumor growth status. DFMO did not increase the efficacy of tamoxifen in inducing tumor regression. PMID- 3084122 TI - Thyrotropin-releasing hormone (TRH) and circulatory shock. AB - Recent research has focused on the potential role of the central nervous system (CNS) in the pathophysiology of circulatory shock. Although the precise role of the brain in shock remains controversial, a number of neuropeptides--through actions within the CNS--appear to play a role in mediating cardiovascular responses to a variety of shock states. Thyrotropin-releasing hormone (TRH) is a neuropeptide that has potent cardiovascular effects within the CNS. Recently, it has been used successfully to reverse shock of varying etiologies in a number of species. Here we review the cardiovascular actions of TRH, its interaction with endogenous opiate systems, and its potential role in the treatment of circulatory shock. PMID- 3084123 TI - General effect of endotoxin on glucocorticoid receptors in mammalian tissues. AB - Considering the ubiquitous nature of glucocorticoid actions and the fact that endotoxin inhibits glucocorticoid action in the liver, we proposed to examine whether endotoxin affected extrahepatic actions of glucocorticoids. Fasted C57BL/6J mice were injected intraperitoneally with endotoxin (LD50) at 0800 and were killed 6 h later. Control mice were injected with an equal volume of saline. 3H-dexamethasone binding, measured by a new cytosol exchange assay utilizing molybdate plus dithiothreitol, in liver, kidney, skeletal muscle, spleen, lung, and heart tissue was significantly lower in treated than in control mice. The equilibrium dissociation constants were not significantly different, but the number of available binding sites in each tissue was reduced by endotoxin treatment. Phosphoenolpyruvate carboxykinase activity was significantly reduced in liver but not in kidney. Endotoxin treatment lowered glycogen content in liver but not in skeletal muscle. The reduction observed in the "a" form of liver glycogen synthase due to endotoxin was not seen in skeletal muscle glycogen synthase "a." These data support the proposal that endotoxin or a mediator of its action inhibits systemic glucocorticoid action. The results also emphasize the central role of the liver in the metabolic disturbances of the endotoxin-treated mouse. PMID- 3084124 TI - Vasoconstriction of stenotic coronary arteries during dynamic exercise in patients with classic angina pectoris: reversibility by nitroglycerin. AB - To study the vasomotility of normal and diseased coronary arteries during dynamic exercise, symptom-limited supine bicycle exercise during cardiac catheterization was performed by 18 patients with classic angina pectoris. The cardiovascular response was assessed by hemodynamic measurements and computer-assisted determination of normal and stenotic coronary artery luminal areas from biplane coronary angiograms made before, during, and after exercise. After baseline measurements were recorded, 12 patients (group 1) performed bicycle exercise for 3.4 min (mean), reaching a maximum workload of 81 W (mean); at the end of exercise they received 1.6 mg sublingual nitroglycerin. After measurements at rest in six other patients (group 2), 0.1 mg intracoronary nitroglycerin was given, followed by exercise (3.8 min, 96 W; NS) and sublingual nitroglycerin as in group 1. During exercise in group 1, luminal area of the coronary stenosis decreased to 71% of resting levels (p less than .001), while area of the normal coronary artery increased to 123% of control (p less than .001). After sublingual nitroglycerin at the end of exercise, area of the normal vessel further increased to 140% of control (p less than .001), while luminal area of the stenosis dilated to 112% of resting levels (p less than .001 vs exercise, NS vs rest). Pretreatment with intracoronary nitroglycerin increased both normal (121%; p less than .05) and stenotic (122%; p less than .05) luminal areas, while preventing the previously observed narrowing of stenosis during exercise (114%; NS). Exercise resulted in a similar heart rate-systolic pressure product and caused angina pectoris in two-thirds of the patients in each group. However, patients pretreated with intracoronary nitroglycerin (group 2) had a lower mean pulmonary arterial pressure during maximum exercise (35 mm Hg) than those patients (group 1) not receiving pretreatment (47 mm Hg; p less than .001). Group 2 patients reached a percentage of their predicted work capacity (65%) that was about the same as that during previous upright bicycle exercise (71%; NS), while group 1 patients had a significantly lower work capacity (51% of predicted) than that before catheterization (82%; p less than .001). Hence, narrowing of coronary artery stenosis during dynamic exercise is attributable to active vasoconstriction due to its reversibility by preexercise intracoronary nitroglycerin. Patients who did not experience narrowing of stenosis during exercise (group 2) had less evidence of myocardial ischemia (lower mean pulmonary arterial pressure) and maintained their work capacity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3084125 TI - Plasma apoproteins and the severity of coronary artery disease. AB - Plasma levels of lipids, lipoproteins, and apoproteins in 281 patients undergoing cardiac catheterization were correlated with the incidence and severity of coronary artery disease (CAD) to determine if measurements of apoprotein levels are more predictive of the presence and severity of CAD than the corresponding levels of lipoprotein lipids. In 156 men with CAD among 194 men in the study the only variable other than age that correlated with the severity of CAD, defined by the number of lesions and percent stenosis, was the ratio of apoprotein AI to apoprotein B (r = .1908, p less than .03). The ratio of apoprotein AI to apoprotein B was a more accurate predictor of the severity of CAD than was the ratio of the corresponding high-density to low-density lipoprotein levels (coefficients of partial determination of .07 and .035; p less than .001 and p less than .07, respectively). Multivariate analysis confirmed the independent effect of the ratio of apoprotein AI to apoprotein B on the severity of CAD even after adjustments were made for lipid levels, age, presence of hypertension or diabetes, and therapy with beta-blockers or diuretics. Among men with total occlusion of a coronary artery apoprotein E and apoprotein B levels were significantly higher than in control subjects with a similar extent of CAD (p less than .03). The lipid profiles of the 37 women with CAD were very different from those of the men.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084126 TI - The effect of nitroglycerin on forearm arterial distensibility. AB - Nitroglycerin acts, in part, to reduce arterial impedance, and thus left ventricular work. The reduction in arterial impedance is largely attributable to a fall in systemic vascular resistance, but may also be due to an increased distensibility of the arterial tree. In this study, volume distensibility of forearm arteries was calculated from measurements of pulse-wave velocity before and during intravenous nitroglycerin infusion. Since a fall in blood pressure itself increases arterial distensibility, the induced blood pressure change was controlled as a variable by repeating the measurements with the subject's forearm in a plastic cylinder and repeating the measurements at a variety of altered cylinder pressures. At every studied pressure, nitroglycerin infusion increased forearm arterial distensibility, demonstrating another way in which nitroglycerin reduces left ventricular afterload. Since the pulsatile portion of cardiac work is approximately 10% of total work, the magnitude of this nitroglycerin effect on cardiac function is probably small. PMID- 3084127 TI - Pharmacodynamics of tissue-type plasminogen activator characterized by computer assisted simulation. AB - Prospective characterization of pharmacodynamics of tissue-type plasminogen activator (t-PA) is needed for diverse clinical applications. Accordingly, we used physiologically based, computer simulation of participating biochemical reactions in response to concentrations of circulating t-PA seen with infusions of 1 to 7 hr duration in 45 patients. Predicted values were compared with those from a "training set" obtained in six patients given t-PA for coronary thrombosis and six receiving therapy for peripheral arterial occlusion. Subsequently, results of simulation were compared prospectively with observations from a "test set" of 33 consecutive patients given low doses of t-PA for as long as 7 hr or higher doses for 1 to 2 hr and with data from 101 patients given t-PA in the European Cooperative Trial. Fits between observed and predicted values were close. Based on observations in the training set, the alpha 2-macroglobulin reaction with circulating plasmin and ongoing synthesis of plasminogen were incorporated in the simulations. Fibrinogenolysis in vitro was documented despite supplementation of samples with aprotinin, particularly when concentrations of t PA were high. This phenomenon can lead to overestimation of fibrinogen depletion and was found to be obviated by the use of PPACK, a novel serine protease inhibitor. Results indicate that the simulation approach developed permits economic, prospective evaluation of regimens of t-PA suitable for diverse conditions and delineation of the impact of individual constituents and reactions on pharmacodynamics of t-PA and on the risk of induction of a systemic lytic state. PMID- 3084128 TI - Effects of encainide and its metabolites on energy requirements for defibrillation. AB - Encainide, a class IC antiarrhythmic agent, has been associated with proarrhythmic responses of ventricular tachycardia and fibrillation requiring defibrillation in patients. We examined the short-term effects of intravenous encainide and its two major metabolites, O-demethyl-encainide (ODE) and 3-methoxy ODE (MODE), on the energy requirements for successful defibrillation in 25 pentobarbital-anesthetized, open-chest dogs. Truncated exponential (60% tilt) defibrillation shocks were administered through right atrial spring and left ventricular epicardial patch electrodes identical to those used in man with the automatic implantable defibrillator. At baseline multiple shocks of varying energy were applied to construct curves of percent successful defibrillation as a function of energy (DF curves) for each animal. Encainide, ODE, or MODE was then infused in loading and maintenance doses to achieve QRS widening of 20% to 50%. Saline was administered to animals serving as controls. Determination of the DF curve was repeated, after which the infusion was discontinued. After 1 hr washout period, an additional DF curve was constructed. The data were analyzed by logistic regression, and the energies required for 50% successful defibrillation (E50) were compared. No significant differences existed between the four groups in body or heart weight, extent of QRS widening, or baseline E50 values. After administration of encainide and ODE, the E50 increased by 129 +/- 43% (p less than .001) and 76 +/- 34% (p less than .005), respectively. Return of E50 toward baseline was observed after the washout periods in both groups (p less than .025), demonstrating the reversibility of the drugs' effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084129 TI - Radioimmunoassay of laminin in serum and its application to cancer patients. AB - In this sensitive radioimmunoassay for laminin fragment P1 (purified from pepsin extracts of human placenta), monovalent antibody fragments obtained from rabbit antisera against the laminin component are used. The inhibition assay showed a low intra- and interassay variability, and the inhibition curves for various serum samples had parallel slopes. Molecular-sieve chromatography demonstrated heterogeneity of the laminin antigen in serum. For quantification we defined arbitrary units based on the amount of antigenic material present in normal human serum. Sera from 361 tumor patients showed increased values in about half of the cases. Correlation with increased concentration of carcinoembryonic antigen was poor (r = 0.259). The assay may be useful for diseases involving basement membrane metabolism. PMID- 3084130 TI - Homogeneous apoenzyme reactivation immunoassay for thyroxin-binding globulin in serum. AB - In this automated apoenzyme reactivation immunoassay system (Ames Optimate) for thyroxin-binding globulin (TBG), the sample and N6-aminohexylflavin adenine dinucleotide-labeled TBG react sequentially with antiserum. Then apoglucose oxidase is added to combine with the free fraction and generate glucose oxidase activity, which is measured colorimetrically. The assay requires 100 microL of sample and covers the clinically significant range for TBG (less than 2.5 to 55 mg/L). The first result is obtained in 16 min; assay of 29 samples and their blanks is completed in less than 1 h. The lower limit of detection is about 2.5 mg/L. Between-assay CVs (n = 9) were less than 9%, within-assay CVs (n = 5) were less than 6%, and analytical recovery of TBG was 103-112%. Reagents are stable at 4 degrees C for at least five months. Results by this method for serum TBG (y) compared well with those determined by radioimmunoassay (x): y = 1.029x--0.352 (r = 0.990, n = 49, Syx = 1.165 mg/L). In addition, with 39 other sera the ratio of total thyroxin (by RIA) to TBG compared well with free thyroxin measured by equilibrium dialysis (r = 0.930) and the free thyroxin index (r = 0.970). PMID- 3084131 TI - Retinol, alpha-tocopherol, lycopene, and alpha- and beta-carotene simultaneously determined in plasma by isocratic liquid chromatography. AB - Retinol, alpha-tocopherol, lycopene, and alpha- and beta-carotene can be simultaneously determined in human plasma by reversed-phase liquid chromatography. Plasma--0.5 mL plus added internal standard, retinyl acetate--is deproteinized with 0.5 mL of ethanol, then extracted with 1.0 mL of petroleum ether. The organic layer is removed and evaporated, the residue is redissolved in 0.25 mL of ethanol, and 8-microL samples are injected into a 60 X 4.6 mm column of Hypersil ODS 3-microns particles at 35 degrees C. An isocratic methanol mobile phase, flow rate 0.9 mL/min, is used for the 9-min run. Retinol and retinyl acetate are monitored at 305 nm, the tocopherols at 292 nm, and the carotenoids at 460 nm. Between-run CVs were 3.1, 6.9, 6.1, and 6.5% for retinol, alpha tocopherol, lycopene, and beta-carotene, respectively. Small sample requirement, simplicity of extraction, short run time, and good reproducibility make this procedure ideal for clinical or research use. PMID- 3084132 TI - Evaluation of simultaneous measurement of lutropin and follitropin with the SimulTROPIN radioimmunoassay kit. AB - We evaluated the analytical performance of the "SimulTROPIN" (Becton-Dickinson Inc.) radioimmunoassay for the simultaneous measurement of lutropin (LH) and follitropin (FSH) in human serum. Dose response, linearity, analytical recovery, sensitivity, and reagent stability were all acceptable. Cross reactivity with other structurally related hormones [choriogonadotropin (CG) and thyrotropin (TSH)] was minimal. A normal reference interval was established for nonmidcycle, ovulatory women. We confirm the low degree of CG and TSH cross reactivity with LH and FSH reported by Becton Dickinson and conclude that this assay is an acceptable method for laboratory use in the simultaneous quantification of these analytes. PMID- 3084133 TI - The usefulness of quantifying kappa and lambda light chains. PMID- 3084134 TI - Differential measurement of monomeric and polymeric IgA by one-directional immunoelectrodiffusion. AB - A technique to specifically quantify monomeric IgA and total IgA in colostrum has been developed using a modified one-dimensional immunoelectrophoretic assay. This method employed electrophoresis in antibody-containing polyacrylamide-agarose gel in the presence of a gel barrier which blocks polymeric IgA. The addition of PEG (polyethylene-glycol 6000) to the anodic gel increased the sharpness of the peaks, the height of which was proportional to the antigen concentration. This method proved to be sufficiently simple, precise, reproducible (CV less than 3%) and linear (from 20-300 mg/l) to measure the monomeric IgA: total IgA ratio rapidly (14 +/- 4.5% for 20 samples in duplicate). Immunoelectrodiffusion studies confirmed that human colostral and serum IgA standards could be used to determine directly monomeric IgA, total IgA and polymeric IgA levels (by difference) rather than to apply correction factors to estimate these IgA levels. PMID- 3084135 TI - Purification of vitamin D binding protein from human plasma using high performance liquid chromatography. AB - Vitamin D binding protein/group-specific component was purified from human plasma by chromatographic techniques utilising high performance liquid chromatography and by traditional low pressure chromatographic techniques alone. Use of high performance liquid chromatography considerably reduced the time taken to prepare pure vitamin D binding protein and increased the yield to 16% compared with 2.8% using the traditional methods. The vitamin D binding protein prepared by high performance liquid chromatography was shown to be highly pure by amino acid sequence, SDS gel electrophoresis and by antibody production. The amino acid sequence was confirmed and extended. The affinity constants of the high pressure liquid chromatography purified vitamin D binding protein for 25 hydroxycholecalciferol (25 OHD3) and 1,25 dihydroxycholecalciferol 1,25(OH)2D3 were 1.9 X 10(7) mol/l and 2.6 X 10(6) mol/l, respectively. PMID- 3084136 TI - Reliability of immunoglobulin determination by two methods. PMID- 3084138 TI - Measurement of radioactivity of pyruvate and other 2-oxo-acids labelled at the 1 position. PMID- 3084137 TI - Involvement of thiol proteases in galactosialidosis. AB - The activities of Z-Phe-Arg-NMec(ZPA) hydrolase, cathepsin B and cathepsin H and the concentration of endogenous thiol protease inhibitor in fibroblasts from patients with galactosialidosis were found not to be significantly different from those in control fibroblasts. Culture for 5 days with thiol protease inhibitors such as leupeptin, E-64 or Z-Phe-Phe-CHN2 partially restored the beta galactosidase activity of fibroblasts from patients, but did not affect the beta galactosidase activity of fibroblasts from control subjects. However, culture with leupeptin, but not other protease inhibitors, increased the ZPA hydrolase and cathepsin B activities of fibroblasts from both patients and controls 2- to 4 fold. Sephadex G-75 chromatography showed that the activity of high molecular weight ZPA hydrolase, which was initially predominant in fibroblasts, decreased markedly during their culture with leupeptin, while the activities of lower molecular weight ZPA hydrolase and cathepsin B increased about 5-fold. These results suggest that high molecular weight ZPA hydrolase, which is presumably cathepsin J, degrades beta-galactosidase, and that the defect in galactosialidosis is impaired protection of beta-galactosidase from degradation. PMID- 3084139 TI - DA/DAPI pattern of marker chromosome: cytogenetics of cat eye syndrome. PMID- 3084141 TI - Results in two infants with the DiGeorge syndrome--effects of long-term TP5. AB - We treated two patients affected by DiGeorge syndrome with long-term administration of the synthetic thymic hormone thymopoietin (TP5). In both cases we obtained durable immunological reconstitution, starting as early as 2 weeks after beginning of TP5 treatment. High levels of circulating immature thymocytes and precursor T cells (defined by monoclonal antibodies OKT6, OKT9, and OKT10) were present prior to therapy, and they steadily decreased during the first few weeks of study. During the same time, phenotypically mature T lymphocytes (OKT3+ and OKT4+/OKT8+) markedly increased, thereafter remaining at near normal levels. OKT10+ cells appeared to rise again after 3 months of TP5 treatment. In vitro function of T cells, assessed by PHA stimulation, and in vivo cell-mediated immunity (skin tests with Candida) were normal at 3 and at 2 months, respectively, after initiation of therapy. No severe infection episodes were recorded and normal development was achieved. No side effect or adverse reaction occurred. In these two patients the other features of the DiGeorge syndrome were successfully treated by early cardiac surgery and vitamin D therapy. The immunological reconstitution, in absence of functioning thymus observed in these two cases, provides further evidence of the effectiveness of long-term treatment with thymic hormones--with maintenance of the improvement of cell-mediated immunity. PMID- 3084140 TI - Neutrophil phagocytosis and killing in insulin-dependent diabetes. AB - Neutrophil phagocytosis and killing of Candida albicans were examined using a radiometric assay in 25 patients with insulin-dependent diabetes and 17 controls under various in vitro metabolic conditions. Glucose was present at 5, 10 and 50 mM, beta-hydroxybutyrate at 1, 5 and 20 mM and glucose with beta-hydroxybutyrate in combinations of 10 with 5 and 50 with 20 mM, respectively. Phagocytosis occurred at similar levels in diabetics and controls at all the glucose and beta hydroxybutyrate concentrations used. The ability to neutrophils from diabetics to kill candida was inhibited by increased concentrations of glucose and beta hydroxybutyrate, both independently and in combination. Candida killing (mean +/- s.e.) was 20 +/- 2.4, 19 +/- 2.3 and 13 +/- 2.7% at glucose concentrations of 5, 10 and 50 mM; and 20 +/- 3.4, 20 +/- 3 and 13 +/- 3% at beta-hydroxybutyrate concentrations of 1, 5 and 20 mM, respectively, and in glucose and beta hydroxybutyrate combinations of 10 with 5 and 50 with 20 mM was 20 +/- 2.8 and 10 +/- 2.8%, respectively. Inhibition was not observed with control neutrophils. These data indicate that although phagocytosis occurs at similar levels in diabetics and controls, killing of candida by the diabetic neutrophil is impaired under conditions of hyperglycaemia and ketosis. The biochemical basis for this effect is discussed. PMID- 3084142 TI - Spontaneous production of eosinophil chemotactic factors by T lymphocytes from patients with subcutaneous angioblastic lymphoid hyperplasia with eosinophilia. AB - Subcutaneous angioblastic lymphoid hyperplasia with eosinophilia (SALH) was reviewed with respect to eosinophil chemotaxis. Lymphoid cells separated from the granuloma spontaneously released at least two different eosinophil chemotactic factors (ECF): low-molecular-weight and high-molecular-weight ECF according to the profile on gel filtration (LMW-ECF, about 500; HMW-ECF, 45,000 to 70,000). The cells, however, failed to produce chemotactic activity for macrophages and neutrophils. By analysis with monoclonal antibodies against lymphocyte subpopulations, the granuloma T cells, probably OKT4-positive cells, were shown to be responsible for spontaneous production of these two ECF. Furthermore, the blood mononuclear leukocytes were separated from the patients with SALH. An ECF closely resembling HMW-ECF was also spontaneously produced by the blood OKT4 positive T lymphocytes, whereas no LMW-ECF was released. Mononuclear leukocytes from healthy donors, however, could produce an ECF resembling HMW-ECF and chemotactic activities for macrophages and neutrophils by stimulation with concanavalin A (Con A). Protein synthesis appeared to be essential for spontaneous ECF and for Con A-induced ECF production. These results suggest that the granuloma OKT4-positive T lymphocytes of the patients with SALH are in activated condition to release LMW- and HMW-ECF, whereas the blood OKT4-positive T lymphocytes are in activated condition to release only HMW-ECF. Such spontaneous and prolonged production of HMW-ECF by the cells can be one of the diagnostic means of SALH. PMID- 3084143 TI - Natural killer cell response to interferons. AB - The availability of recombinant interferons has facilitated a comparison of the in vitro effects of interferon-alpha and -gamma upon human natural killer (NK) cells. In the absence of interferon high and low NK responders exist. Repeated testing of the same individuals revealed different but stable NK patterns to in vitro addition of interferon-alpha and -gamma Furthermore, the NK cell response patterns differed depending on whether the interferons were administered in combination or separately. These studies suggest new complexities that must be addressed in the planning and execution of clinical interferon trials. The pattern of responsiveness of human NK cells to interferon-alpha or -gamma or both is highly variable, but stable, within a given individual. PMID- 3084144 TI - Effects of anti-IgM on mitogen-induced proliferation of human B-lymphocyte malignancies. AB - Therapeutic trials of anti-immunoglobulin antibody have produced a wide range of responses in attempts to control the growth of human B lymphoid neoplasms. This variability might reflect differences in intrinsic functional characteristics of malignant B lymphocytes that determine susceptibility to anti-immunoglobulin mediated regulation of growth. To characterize B-lymphocyte malignancies, tissue samples from 24 patients were studied during short-term culture in vitro. Malignant B lymphocytes were stimulated to proliferate by the T-independent mitogens lipopolysaccharide, cytochalasin B, and Staphylococcus aureus that bears protein A. The effects of monoclonal mouse anti-human IgM on mitogen-induced malignant lymphocyte proliferation were then assessed. Mitogen-induced responses of malignant lymphocytes from three patients were abrogated by 2 micrograms/ml monoclonal anti-human IgM. Proliferation was also abrogated by polyclonal goat anti-IgM antiserum but proliferative responses were not affected by control monoclonal antibody. Further study showed that anti-immunoglobulin-mediated inhibition of proliferation was not dependent on Fc-determined interactions, nor was it dependent on the presence of T lymphocytes. These results indicate that a subset of human B-lymphocyte malignancies are susceptible to inhibition of proliferation mediated by anti-IgM. PMID- 3084145 TI - The demonstration of lupus anticoagulant by an enzyme-linked immunoadsorbent assay. AB - Lupus anticoagulant, an autoantibody associated with thromboembolic disease and pregnancy loss, is currently identified by its capability to prolong phospholipid dependent coagulation tests, such as the activated partial thromboplastin time (APTT). The use of a coagulation assay for the detection of an antibody has several inherent disadvantages: fresh plasma is required for accurate testing, prolongation of coagulation test(s) is not specific for lupus anticoagulant, and coagulation assays are not easily manipulated for the characterization of antigen antibody interactions. Using partial thromboplastin an the antigen, we have developed an enzyme-linked immunoadsorbent assay (ELISA) for the detection of lupus anticoagulant. Fifteen women with lupus anticoagulant (being evaluated for recurrent pregnancy loss or autoimmune disease) and 40 lupus anticoagulant negative controls (including 20 with recurrent pregnancy loss, 12 parous women, and 8 with known autoimmune disease) were evaluated using the APTT and ELISA assays for lupus anticoagulant. All patients with lupus anticoagulant, as defined by the APTT, had significantly elevated IgG (sensitivity and specificity, 100%) or IgG + IgM (sensitivity 93%, specificity 95%) levels compared to controls. PMID- 3084146 TI - Characterization of tissue amyloid by immunofluorescence microscopy. AB - Immunohistochemical classification of amyloid type was possible in 44 of 50 (88%) patients as judged by the concordance of immunofluorescence, clinical, serum, and urine immunoelectrophoresis, and bone marrow data. In frozen tissue sections incubated with a panel of antisera monospecific for immunoglobulin heavy chains, kappa and lambda light chains, and amyloid-A-related protein, the amyloid was classified as AL in 20 and AA in 24. In 6 patients the amyloid could not be classified because of the absence of reactivity in 2 and overlap staining in 4. The findings indicate that routine immunofluorescence examination of diagnostic biopsies is an important adjunct in the classification of amyloid. PMID- 3084147 TI - Renal transplantation in light chain nephropathy: case report and review of the literature. AB - A successful cadaveric transplantation in a patient with irreversible renal insufficiency due to light chain nephropathy is reported. Remission of the monoclonal gammopathy was induced with melphalan and prednisone and after 4.5 years of hemodialysis a cadaveric kidney transplantation was performed, which resulted in excellent renal function up to 3.5 years after transplantation. Along with 8 previously reported patients in the literature this case demonstrates that renal transplantation can no longer be withheld from this category of patients, when they are in remission and no other major complications of their monoclonal gammopathy are present. PMID- 3084148 TI - AL-type amyloidosis and light chain deposition disease. PMID- 3084149 TI - Pathoimmune polymyositis induced in C3H/HeJ mice by Trypanosoma cruzi infection. AB - The pathogenic mechanisms related to the development of idiopathic inflammatory skeletal muscle disease are unknown. The myotropic protozoa Trypanosoma cruzi and Toxoplasma gondii are implicated in the induction of myositis in experimental animals (1) and humans (2). In the experiments reported here, a model of pathoimmune myositis is described in C3H/HeJ T. cruzi-infecteed mice. The results showed a significant occurrence of acquired, T. cruzi antigen-dependent spleen T cell cytotoxicity to syngeneic skeletal muscle myoblasts of C3H mice which developed an apparently sterile lymphoid polymyositis. Further experiments with polymyositic C3H mice suggest that spleen B cells do not secrete antibody capable of inducing complement-mediated skeletal muscle myoblast lysis. However, the T. cruzi sensitized splenic lymphocytes did produce a lymphokine which was capable of inducing lysis of syngeneic myoblasts by chromium-51 release assay. PMID- 3084150 TI - Effect of a perfluorochemical emulsion on the development of artificial lung metastases in mice. AB - Intravenous infusions of perfluorochemical emulsions, combined with administration of inspired oxygen or carbogen have been found to improve tumor oxygenation and increase the response of solid tumors in animals to radiotherapy. Fluosol-DA 20 per cent, the only perfluorochemical emulsion currently approved for testing in humans in the United States, has recently entered clinical trials as an adjunct to radiotherapy in the treatment of head and neck carcinoma. The studies reported here were undertaken as part of our laboratory evaluation of the safety and clinical potential of this oxygen-transport fluid as an adjunct to cancer therapy; they asked whether single or multiple treatments with Fluosol and an oxygen-enriched atmosphere produced immunologic perturbations, pulmonary damage, or other effects which altered the development of artificial lung metastases in experimental animals. Neither single nor multiple treatments with clinically relevant regimens of Fluosol and carbogen (95 per cent O2/5 per cent CO2) had any effect on the development of lung nodules from intravenously injected EMT6 tumor cells. PMID- 3084151 TI - Phorbol ester binding and phorbol ester-induced arachidonic acid metabolism in a highly responsive murine fibrosarcoma cell line and in a less-responsive variant. AB - Phorbol ester binding was examined in two lines of murine fibrosarcoma cells. The two cell lines were isolated from the same parent tumor but respond differentially to stimulation with phorbol esters. In one of the lines, these agents stimulate a rapid attachment and spreading response and induce directional migration. The other cell line does not migrate in response to stimulation with phorbol esters and the attachment and spreading response is slow. The cell line which responds actively to phorbol ester stimulation is highly malignant when injected into syngeneic animals while the other line is of low tumorigenicity and is virtually non-metastatic. In spite of these differences, both lines were found in the present study to bind [3H]4 beta-phorbol-12 beta, 13 alpha-dibutyrate in a receptor-mediated fashion. The characteristics of binding were virtually identical between the two cell lines. In additional studies, arachidonic acid metabolism was examined in the same two lines. In the highly responsive line, PMA stimulated a rapid release of [3H]arachidonic acid and its conversion into cyclooxygenase and lipoxygenase products. In the less-responsive line, PMA stimulated a slower release of [3H]arachidonic acid from prelabeled cells. The quantity of arachidonic acid metabolites produced was also much less. These studies suggest that the disparity between the two cell lines in their response to phorbol ester stimulation is not the result of differences in the initial interaction between the cells and ligand but may result from alterations in their signal transductance mechanism. This may be the result of inherent differences in capacity for arachidonic acid metabolism. PMID- 3084153 TI - The critical size defect as an experimental model for craniomandibulofacial nonunions. AB - Little consistency has been manifest among investigators in choosing an appropriate experimental model for maxillofacial bone research. In an effort to develop a protocol for the experimental analysis of maxillofacial nonunions, previous studies using calvarial and mandibular defects as models were reviewed. The creation of nonunions in animals within the calvaria and mandible was size dependent. Defects of a size that will not heal during the lifetime of the animal may be termed critical size defects (CSDs). A rationale was postulated for testing bone repair materials (BRMs) using CSDs in a hierarchy of animal models. This rationale suggests that testing should be initiated in the calvaria of the rat and rabbit, followed by testing in the mandibles of dogs and monkeys. While calvarial CSDs have been established in the rat, rabbit, and dog, further research is necessary to determine the CSD in the calvaria of the monkey, as well as the mandibles of dogs and monkeys. PMID- 3084152 TI - Enhanced tumor metastases upon drug delivery in cross-linked albumin beads. AB - Growth of the murine hepatoma H6 was significantly suppressed by amiloride, a sodium influx inhibitor. Primary tumor growth inhibition was augmented by loading the drug into cross-linked albumin carriers, but lung metastases were enhanced. These results emphasize the importance of using metastatic tumor models when testing new drugs and/or alternative modes of drug delivery. PMID- 3084154 TI - Indium-111 labeled leukocyte imaging following hepatic artery embolization. AB - The use of In-111 labeled leukocytes for abscess localization is becoming well established. The first report of In-111 imaging following hepatic embolization is presented. A 45-year-old man with adenocarcinoma of the colon and metastatic liver disease was treated for intractable pain using particulate embolization of the hepatic artery. In-111 leukocyte imaging was performed to rule out abscess formation. The distribution of the labeled leukocytes demonstrated hepatic uptake commensurate with Tc-99m sulfur colloid (SC) images. Areas of embolization did not accumulate tracer. Pathologic examination at autopsy correlated with the distribution of the labeled leukocytes. Thus, therapeutic embolization did not alter the normal distribution of this tracer in functional hepatic tissue. PMID- 3084155 TI - Prostaglandins and the control of the circulation. PMID- 3084156 TI - Dentine is biochemically abnormal in osteogenesis imperfecta. AB - In osteogenesis imperfecta the bones are brittle but the teeth, whose dentine contains the same genetic collagen as bone (type I), may be clinically normal. To investigate this paradox we have measured the amino acid composition of insoluble dentine collagen from 16 deciduous and 18 permanent teeth in control subjects and in 59 patients with different forms of osteogenesis imperfecta. In 55 of the patient samples significant differences from normal were found, especially in the number of lysine residues, and in the relative amounts of hydroxylysine to lysine. These results demonstrate the high frequency of biochemical abnormalities in osteogenesis imperfecta. They also suggest that classifications of this disorder based on the presence or absence of clinical dentiogenesis imperfecta are likely to be unsound. PMID- 3084157 TI - Protein losing enteropathy associated with Nippostrongylus brasiliensis infestation and its impact on albumin homoeostasis in rats fed two levels of dietary protein. AB - Alterations in plasma albumin concentration and gastrointestinal permeability have been investigated in rats infected with the nematode Nippostrongylus brasiliensis and fed adequate or low protein diets. Infection caused only minor changes in growth and food consumption of well nourished rats but resulted in significant reductions in those fed the low protein diet. Animals in both dietary groups were able to mount an immune response beyond day 10 post-infection (p.i.) which caused expulsion of the parasites, but this was less effective in rats fed the low protein food. Uninfected rats fed the low protein diet had significantly lower plasma albumin concentrations than their well nourished counterparts. Animals of both dietary groups showed a progressive reduction in plasma albumin concentration as the infection developed but values returned towards normal as the parasites were expelled. The reduction in plasma albumin concentration was closely associated with increases in gastrointestinal leakage of plasma protein but losses were far greater in the protein deficiency animals. Beyond day 10 p.i. protein loss decreased in both dietary groups and by day 21 p.i. had returned to normal in well nourished animals but not those fed the low protein diet. Intestinal permeability measured by the lactulose:mannitol ratio technique gave similar results to the protein loss data. Permeability increased as the infection progressed then fell as the worms were expelled but remained above control values in infected protein deficient animals. Overall, animals fed the low protein diet were more severely affected by the parasite than were their well fed counterparts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084158 TI - [Current status of antibiotic therapy in the surgical field]. PMID- 3084159 TI - [Evaluation of the use of small doses of insulin in continuous venous infusion in ketoacidotic coma]. PMID- 3084160 TI - Use of nucleic acid probes for the detection of sexually transmitted infectious agents. AB - Deoxyribonucleic acid sequences specific for a pathogen of interest can be isolated from a variety of microorganisms. Such DNA probes can be exploited to detect infectious agents directly in infected patient material despite the presence of large numbers of other organisms and host DNA. This technology is dependent upon the recognition of a specific nucleotide sequence present in DNA extracted from a clinical sample by a radiolabeled or nonisotopically labeled DNA probe. We have isolated several DNA probes for the detection of pathogenic Neisseria which include a plasmid species unique to the gonococcus, as well as several cloned genes that detect both the gonococcus and the meningococcus. In addition, we characterized a unique plasmid of Chlamydia trachomatis that has proved to be quite useful as a DNA probe for the detection of this pathogen in cervical secretions and, by in situ hybridization, in Papanicolaou smears. Deoxyribonucleic acid hybridization as a diagnostic tool is still in its infancy. It holds a number of advantages over conventional methods of pathogen detection and serves as an alternative, as well as a complement, to available immunologic methods. PMID- 3084161 TI - Effect of diagnosis-related groups on diagnostic methodology in the hospital laboratory. AB - Traditionally physicians have ordered clinical laboratory tests for a variety of reasons. The establishment of a federally mandated prospective payment system for Medicare patients based on diagnosis-related groups has, among other things, necessitated a review of these reasons as well as the level of use of clinical laboratory services for a given diagnosis. Diagnosis-related group payment to hospitals is independent from the number of laboratory studies performed as long as the diagnosis-related group diagnosis is substantiated at the time the patient is discharged from the hospital. The cost-effective utilization of present tests as well as the adoption of new diagnostic methodologies depends on the assessment of whether a test possesses the appropriate parameters to be of sufficient diagnostic value. These factors include sensitivity, specificity, prevalence, speed, and the costs associated with false-negative or false-positive results. The assessment of the diagnostic value of present or future laboratory methods will require careful analysis relative to their financial impact both within the laboratory and for the hospital as a whole. The laboratory's knowledge of the diagnosis-related group accounting for the highest percentage of their hospital's costs, the highest volume of their cases, and the highest use of their services can aid in assessment of the appropriateness and level of laboratory services. An analysis of the percentage of microbiology costs associated with these diagnosis related group categories for a large, tertiary care hospital is discussed. PMID- 3084162 TI - Diagnosis of Neisseria gonorrhoeae and Chlamydia trachomatis infections using antigen detection methods. AB - Rapid antigen detection methods have great potential value in managing sexually transmitted gonococcal and chlamydial infections. Ideally, such tests should be rapid, technically simple, inexpensive, accurate, and applicable to all sites of infection commonly sampled (cervix, urethra, pharynx). For gonorrhea, the Gram stain fulfills these criteria in men with symptomatic urethritis, but lacks sensitivity when used at other sites or in asymptomatic patients. Antigen detection for gonorrhea would thus be of greatest value in 1) the diagnosis of gonococcal cervical infections in women with mucopurulent cervicitis or pelvic inflammatory disease, 2) the diagnosis of gonococcal proctitis in homosexual men, and 3) in situations requiring lengthy specimen transport. Because culture confirmation of Chlamydia trachomatis infections is not widely available, antigen detection tests could be of great value in management of these infections. Major uses include 1) confirming infection in women with cervicitis, endometritis, and pelvic inflammatory disease; 2) screening for asymptomatic infections in high risk groups of women; and 3) confirmation of Chlamydia trachomatis infections in infants and in adult males. The currently available methods for diagnosis of gonococcal and chlamydial infection by antigen detection are reviewed herein. Continued experience with antigen detection tests in well defined populations having high and low risk of gonococcal and chlamydial infection is needed to more fully determine how best to utilize these assays. PMID- 3084163 TI - Diagnosis and management of Paget's disease. PMID- 3084164 TI - Anemia in the aged: an update. PMID- 3084165 TI - Using diagnosis-related groups in the NHS. PMID- 3084166 TI - Abnormal endocrine profile among women with confirmed or presumed ovulation during long-term Norplant use. AB - FSH, LH, estradiol and progesterone were serially assayed during 8 cycles of six subjects using six subdermal implants releasing levonorgestrel (NORPLANT) for a period of 2 to 6 years. All 8 cycles studied had a very low LH peak and a low or nonexistent FSH peak as compared to 8 control cycles. The mean LH peak for NORPLANT users was 33.9 mIU/ml as compared to 142 mIU/ml in the control group; and FSH was 13.0 mIU/ml as compared to 31.3 mIU/ml in controls. A subsequent rise in progesterone was observed in the 8 cycles studied, but the mean mid-luteal levels were significantly lower than in controls (9.0 ng/ml vs. 15.6 ng/ml). No differences were observed in the estradiol curve. Two of the subjects using NORPLANT had a laparotomy performed on days 17 and 20 of the cycle, for surgical sterilization purposes. A distinctive corpus luteum with a stigma was observed. Our results indicate that women under prolonged use of NORPLANT do not have normal endocrine cycles, even though they may ovulate. It is doubtful however, that these ovulatory cycles can be fertile under the abnormal endocrine conditions found in our subjects. In addition to the possible effect of luteal insufficiency, the normal maturation of the oocyte may be impaired. PMID- 3084168 TI - Haemodynamic and humoral reaction in arterial hypertension during acute blood pressure lowering induced by nitroglycerin. AB - The aim of the study was to test whether there are typical changes in haemodynamics and humoral regulation in untreated hypertensives compared to normotensives with acute lowering of blood pressure (and venous return) induced by nitroglycerin (NTG). 23 hypertensives were investigated by radiocardiography and microcatheterization of the pulmonary artery as well as by means of humoral analyses in comparison to 10 normotensives. After performing the studies at rest and during exercise, 0.8 mg NTG was given and the investigations were repeated. There were only insignificant differences in cardiac output and left ventricular filling pressure (PAEDP) at rest and during exercise between both groups. The pressure reductions due to NTG were also similar. Plasma renin activity and plasma kallikrein did not differ in hypertensives and normotensives either at rest and during exercise or after NTG. The prostaglandins (PgE, PgF2-alpha, PgI) were extremely variable. In hypertensives, only PgI was decreased, with increase after NTG, at rest. Thus, PgI is the only humoral indicator participating in blood pressure lowering induced by NTG. PMID- 3084167 TI - Five years' experience with levonorgestrel-releasing IUDs. AB - Two levonorgestrel-releasing IUDs and a copper-releasing IUD of the same shape were studied in a randomized comparative study over five years. The levonorgestrel-releasing IUDs released 20 micrograms or 30 micrograms per day. The Pearl index during the 10,600 woman-months of LNG-IUD use was 0.11. The control device releasing copper had a Pearl index of 1.6. The amount and duration of menstrual bleeding was greatly reduced, leading to a high incidence of oligo- or amenorrhea. The continuation rate in this pioneer trial was 53 per 100 users for the levonorgestrel-releasing IUD (LNG-IUDs) and 50 per 100 users for the copper-releasing IUD (Nova T). The removal rates for reasons other than amenorrhea were not significantly different. Discontinuation because of amenorrhea occurred during the first two years, the cumulative termination rate for this reason was 11.6 per 100 users at five years. The LNG-IUDs removed for investigation after five years of use revealed that the devices contained about 40 percent of the original load. The effective lifespan of the device has been demonstrated by this study to be five years; the residual steroid gives an additional safety period of two more years. The LNG-IUD is a highly effective reversible contraceptive method, which strongly reduced the amount and duration of bleeding. During the first two months there is scanty but frequent spotting which, like the high incidence of oligo- and/or amenorrhea, requires counselling of health personnel and women using LNG-IUDs. PMID- 3084169 TI - Effect of 6-hydroxydopamine on heart lipoprotein lipase activity in mice. AB - The effect of 6-hydroxydopamine (6-OHDA) on heart lipoprotein lipase (LPL) activity in mice was investigated in vivo and in vitro. Intraperitoneal administration of 6-OHDA (30 mg/kg b. w.) provoked a statistically significant (p less than 0.05) increase in heart LPL activity and a significant fall (p less than 0.05) in post-heparin lipolytic activity (PHLA) in blood serum, compared with controls. However, injection of heparin (10 IU/100 g b.w. i.p.) and 6-OHDA provoked a fall in heart LPL activity to values similar to those found in controls and an increase in serum PHLA, although not so high as in animals injected with heparin alone. Adrenalectomized mice to which 6-OHDA was administered showed values of heart LPL activity similar to control animals, while heart LPL activity in the 6-OHDA group was significantly higher compared with controls (p less than 0.01). Administration of 6-OHDA in vitro to heart homogenate significantly increased LPL activity, whether or not heparin was present in the incubation medium (p less than 0.0005). PMID- 3084170 TI - Intralipid disappearance in critically ill patients. AB - Intralipid elimination patterns were compared in 25 healthy controls, 12 patients recovering from uncomplicated cholecystectomy, and 25 critically ill patients. The intravenous fat tolerance test revealed a similar fractional removal rate (k2) in healthy controls and critically ill patients, but k2 was increased in cholecystectomy patients. The concentration of cross-reactive protein (CRP) correlated positively to the concentration of total triglyceride and low-density lipoprotein-triglyceride, and negatively to low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol. The extrapolated zero-time concentration of Intralipid in the critically ill patients was only one-third of the value in healthy controls. After this initial loss, however, Intralipid was removed from the circulation after first-order kinetics. These low concentrations of Intralipid were not correlated with concentrations of CRP. Possible explanations for this phenomenon include a change in the configuration of the lipid particles, the so-called creaming phenomenon, and/or immediate and substantial uptake of the emulsion by certain organs. PMID- 3084171 TI - Hemodialysis using gabexate mesilate (FOY) in patients with a high bleeding risk. AB - The efficacy of gabexate mesilate (FOY), a synthetic serine proteinase inhibitor, was compared with that of heparin in preventing the acceleration of bleeding after hemodialysis. Transfused blood volume (TBV) was measured 24 h before and after 24 dialyses in 14 bleeding patients with impaired hemostatic function. The predialysis TBV did not differ significantly between heparin and FOY groups; however, TBV was significantly (p less than .05) larger after heparin dialysis than after FOY dialysis. After dialysis, TBV was increased in eight of nine heparin patients, compared to only three of 15 FOY subjects (p less than .01). FOY is an effective agent and may decrease postdialysis bleeding complications in certain high-risk patients. PMID- 3084172 TI - Hydrostatic determinants of cerebral perfusion. AB - We examined the cerebral blood flow response to alterations in perfusion pressure mediated through decreases in mean arterial pressure, increases in cerebrospinal fluid (CSF) pressure, and increases in jugular venous (JV) pressure in 42 pentobarbital anesthetized dogs. Each of these three pressures was independently controlled. Cerebral perfusion pressure was defined as mean arterial pressure minus JV or CSF pressure, depending on which was greater. Mean hemispheric blood flow was measured with the radiolabeled microsphere technique. Despite 30-mm Hg reductions in mean arterial pressure or increases in CSF or JV pressure, CBF did not change as long as the perfusion pressure remained greater than approximately 60 mm Hg. However, whenever perfusion pressure was reduced to an average of 48 mm Hg, cerebral blood flow decreased 27% to 33%. These results demonstrate the capacity of the cerebral vascular bed to respond similarly to changes in the perfusion pressure gradient obtained by decreasing mean arterial pressure, increasing JV pressure or increasing CSF pressure, and thereby support the above definition of cerebral perfusion pressure. PMID- 3084173 TI - Evaluation of the sterility of thermodilution room-temperature injectate preparations. AB - This study assessed the bacteriologic safety of room-temperature injectate used for cardiac output measurement in a surgical ICU, and compared its cost/benefit relationship to that of prefilled packaged syringes and a closed-loop injectate system. Ninety-five samples of injectate were obtained at four time intervals from staff-prepared syringes, and cultured for microbiologic growth. About 29% (27/95) of samples yielded bacterial growth, ranging from two colony-forming units to those too numerous to count. All positive samples contained skin flora, including coagulase-negative staphylococci and coryneforms. Additionally, five plates contained colonies of Gram-negative bacteria. Extended storage time increased the risk of contamination: 16.2% were contaminated within the first 24 h, whereas 45% were contaminated when stored for more than 72 h. Switching to a closed injectate system significantly (p less than .001) decreased the incidence of contamination by 1.2%, and also allowed a cost savings of $1.52/patient. PMID- 3084174 TI - Osmotic stress as a factor in the detrimental effect of glycerol on human platelets. AB - The aim of this work was to determine the importance of osmotic stress as a damaging factor in the detrimental effect of glycerol on human platelets. The severity of osmotic stress was mitigated by reducing the rate of change of glycerol concentration in the suspending medium. The classical permeability equations were used to predict cell volume changes in response to step changes in extracellular glycerol concentration. Protocols were devised that limited cellular shrinkage during glycerol addition and cellular swelling during glycerol dilution. When glycerol was added and diluted rapidly, the recovery of the hypotonic stress response with respect to untreated controls was unaffected by 0.25 mol/liter glycerol, but was reduced to ca. 65% after exposure to 0.5 mol/liter glycerol and to ca. 25% after exposure to 1 mol/liter glycerol. When 1 mol/liter glycerol was added and removed slowly such that cell volume remained within the range of 60-130% of normal volume, recovery of the hypotonic stress response was improved to ca. 50%, and the aggregation response was undiminished. Osmotic stress was therefore at least partly responsible for the damage caused by glycerol. However, platelets were damaged more after slow dilution from 1 mol/liter glycerol, when cellular swelling was limited to 116% of normal volume, than after rapid dilution from 0.25 or 0.5 mol/liter glycerol, which resulted in cellular swelling to 123% and 146% of normal volume, respectively. Thus, a possible toxic effect of glycerol cannot as yet be discounted. PMID- 3084175 TI - An approach to cost-effective education in the critical care setting. PMID- 3084176 TI - Investigation of drug interactions with pinaverium bromide. AB - A series of studies was carried out at 6 centres to investigate possible drug interaction between the spasmolytic, pinaverium bromide, and cardiac glycosides, anticoagulants and hypoglycaemic agents given to patients as part of the long term treatment of their condition. The results of clinical and laboratory investigations did not show any evidence of pinaverium bromide interfering with the action or activity of any of the drugs studied. PMID- 3084177 TI - The new economics of psychiatry. PMID- 3084178 TI - Psychiatry 1986: the state of the profession. PMID- 3084179 TI - Interferon and growth factor activity for human lung fibroblasts. Release from bronchoalveolar cells from patients with active sarcoidosis. AB - Pulmonary sarcoidosis is a granulomatous disorder of unknown etiology characterized by both an active cellular immune process and interstitial fibrosis. It has recently been demonstrated that gamma-interferon (the type of interferon associated with an active cellular immune process) is also a potent growth factor for human lung fibroblasts. To evaluate the hypothesis that there is an association between the release of immune interferon and the release of growth factor activity for fibroblasts, bronchoalveolar cells from patients with sarcoidosis were studied for the spontaneous release of both immune interferon and growth factor activity for fibroblasts. Bronchoalveolar cells from 11 of the 24 patients spontaneously released gamma-interferon in vitro. Supernatants from sarcoidosis patients whose bronchoalveolar cells released interferon contained a significantly higher percentage of lymphocytes than those whose bronchoalveolar cell supernatants did not contain interferon (p less than 0.01). Fibroblast growth was also significantly augmented by supernatants from sarcoidosis patients whose bronchoalveolar cells released gamma-interferon compared to supernatants which did not contain interferon (p less than 0.05). In patients with focal abnormalities on chest x-ray films, there was significantly more interferon released by bronchoalveolar cells from the areas that were most abnormal compared to more normal areas of the lung. These studies suggest that there is an association between the release of immune interferon and release of growth factor activity for fibroblasts by bronchoalveolar cells from patients with active pulmonary sarcoidosis. PMID- 3084180 TI - Importance of adequate gas-mixing in contrast echocardiography. AB - Microbubble formation has been accepted as the mechanism producing contrast echoes. Comparisons of the contrast effects of various agents have been studied extensively, but the importance of gas-mixing has been less appreciated. To test the hypothesis that good gas-mixing, by facilitating microbubble formation, would enhance contrast effect, this study compared the contrast echocardiograms of ten adult patients before and after mixing carbon dioxide with various contrast agents. Contrast agents tested included a 5 percent glucose in water, vitamin B complex, vitamin C, and Cardiogreen solutions. First, we recorded echocardiograms by injecting each diluted contrast solution alone, then repeated the examinations using 10 ml of each diluted solution with 1 ml of carbon dioxide (CO2), mixed by means of a four-way stopcock. Satisfactory or excellent results were obtained in seven of ten, ten of ten, ten of ten, and ten of ten tests, respectively, after thorough gas-mixing, vs one of ten, seven of ten, eight of ten, and six of ten, respectively, before gas-mixing. We conclude that the addition of sufficient amounts of gas, followed by thorough mixing, is of great importance in contrast echocardiography. Consistently good results can be achieved with vitamin C, vitamin B or Cardiogreen solutions by this simple and safe method. PMID- 3084181 TI - Prospective payment. A procrustean paradigm. PMID- 3084182 TI - Hypercarbia during weaning. Nutritional support. PMID- 3084183 TI - Behavioral competence of maltreated children in child care. PMID- 3084184 TI - Cytogenetic characterization of the 4BC region on the X chromosome of Drosophila melanogaster: localization of the mei-9, norpA and omb genes. AB - Thirty genetic alterations, which involve the 4BC region of the Drosophila X chromosome, have been induced by ionizing radiation or by an endogenous mutator element. These mutations were recovered by screening for reversion of the dominant mutants Oce and Qd or for induction of the recessive mutants bi and rb. Among the 23 mutants generated by ionizing radiation, 20 have proven to be cytologically detectable chromosomal aberrations. Seven additional unique aberrations were generated in the Uc mutator strain. In total, 22 cytologically detectable deficiencies, 3 translocations, 1 inversion, 1 transposition, and 3 cytologically normal mutants have been recovered. Complementation analysis has permitted the cytogenetic localization of eight genes in the 4BC region. The mei 9 locus has been assigned to region 4B4-6, because this function is carried by Df(1)rb41 but not by Df(1)biD1. The norpA locus has been placed in the 4B6-C1 region based on its location between the distal breakpoints of Df(1)biD2 and Df(1)rb41. The genes lac, Qd, bi, and omb are localized to bands 4C5,6, rb to 4C6 and amb to 4C7,8. With one exception the complementation analysis has also permitted a determination of the linear sequence of these genes. This cytogenetic localization of these loci will facilitate the cloning and molecular analysis of genes controlling a key function in DNA repair and recombination (mei-9), and two fundamental neural functions (norpA and omb). PMID- 3084185 TI - Diverticular disease of the large bowel in Singapore. An autopsy survey. AB - One thousand fourteen consecutive large intestines were removed at autopsy from persons over the age of 14 years and examined for diverticular disease. Diverticulosis was encountered in 194 patients (19 percent). The lesion appeared early in life, after the second decade. Men were affected more frequently than women before the age of 60 years. Chinese men had significantly more diverticular disease than Malayan men (P less than 0.01) and Indian men (P less than 0.02). Chinese men also had significantly more diverticular disease than Chinese women. There was a predominance of right colon involvement, with the disease affecting especially the ascending colon and cecum. This pattern was observed in all three major ethnic groups, and in both the Singapore-born and foreign-born Singaporeans. The cause of right-sided diverticulosis is unknown. It appears that, while adoption of the western diet may influence the prevalence of diverticular disease, the site of predilection is determined more by racial or genetic predisposition. All diverticula examined histologically were false, including 39 (20 percent) solitary diverticula. The distribution of solitary diverticula was similar to that of multiple diverticulosis. It is suggested that solitary and multiple diverticulosis are part of the spectrum of the same disease. PMID- 3084187 TI - [Effect of concanavalin A and the Ca2+ ionophor A 23187 on the differentiation of the Rana temporaria gastrula ectoderm in vitro]. PMID- 3084186 TI - Jejunostomy feeding in the management of gastroparesis diabeticorum. PMID- 3084188 TI - [Effect of space flight factors on recombination frequency in Drosophila melanogaster]. PMID- 3084189 TI - [Activation of protein kinase by estradiol in plasma membranes of estradiol dependent tumors]. PMID- 3084190 TI - Anionic glycerophospholipids in platelets from alcoholics. AB - Studies on ethanol-exposed animals have revealed changes in anionic phospholipids in brain membranes. The intention of this study was to investigate whether there was a similar effect on man. Assuming platelets to be an adequate model for CNS synaptosomes, concentration and fatty acid composition of anionic phospholipids, phosphatidylserine (PS) and phosphatidylositol (PI) in the platelet membrane from alcoholics after a debauche period were examined and compared to controls. Ethanol effects on neutral lipids were also analysed in order to obtain a comprehensive view. No quantitative difference was found in anionic phospholipids between alcoholics and controls. Fatty acid composition of individual phospholipids revealed significant changes which were more obvious in neutral phospholipids than in anionic. Oleic acid was increased and linoleic and arachidonic acids were decreased. After 1 week of detoxification, the abnormalities did not decrease, on the contrary they increased and total phospholipid concentration per platelet was significantly higher than in controls. It is concluded that the ethanol toxicity on bone marrow hampers the use of platelets as a model for synaptosomes but that the observed lipid abnormalities might play a major role in the impairment of platelet function in alcoholics. PMID- 3084191 TI - Glycoprotein sialyl- and galactosyl transferase activities in erythrocyte membranes in alcoholic patients and healthy controls. AB - In investigating possible mechanisms underlying carbohydrate deficiencies in serum transferrin and erythrocyte membranes in alcoholics, a total of 27 alcoholic patients and 27 healthy controls were examined for the activities of sialytransferase in serum and erythrocyte membranes and galactosyltransferase in erythrocyte membranes. The enzymes were assayed with endogenous and different exogenous glycoprotein acceptors and with [14C] CMP-sialic acid and [14C] UDP galactose as substrates. No decrease in enzyme activities were found in alcoholic patients compared to controls, indicating that chronic ethanol abuse does not exert any direct inhibitory effect on these glycosyltransferases in isolated erythrocyte membranes or on sialytransferase in serum. Further studies of the effect of ethanol on the metabolism of complex carbohydrates are clearly necessary. PMID- 3084192 TI - Comment: ASPEN's exclusion of Pharm.D.s. PMID- 3084193 TI - [Internal disease findings in Arndt-Gottron scleromyxedema]. AB - A case of papular mucinosis (scleromyxoedema of Arndt-Gottron) in a 64-year-old man is reported. Although a cutaneous mucinosis, the disease is characterized by a number of systemic disorders which determine the course and prognosis of the disease. A survey of 57 reported cases reveals that, in addition to the obligatory paraproteinaemia, neurological (24% of cases), cardiovascular (10%) and myopathic (9%) symptoms are in the foreground. Systemic lymphoplasmo reticular involvement occurred in 14%. These findings emphasize the need for interdisciplinary cooperation in the diagnosis and for long-term supervision of patients with this disease. PMID- 3084194 TI - [Organ-specific intestinal antigens contained in tumors of the human gastrointestinal tract]. AB - Two organospecific antigens were found in extracts of human fetal intestinal mucosa. One of them is destroyed by boiling and its electrophoretic mobility corresponds to that of beta 1-globulins. On the contrary, the other antigen is thermostable and its electrophoretic mobility corresponds to alpha 2 globulins. Other properties of these antigens are similar. The comparison of the test systems to these antigens in double immunodiffusion showed that they reacted with each other making a "spure", but these antigens immunologically differ from CEA. Both of organospecific antigens were determined in all extracts of nonmalignant specimens of definite intestinal and colon mucosa and in most extracts of colon tumours. These antigens are usually absent in extracts of other normal and tumour tissues. These antigens are suggested to be of use as tumour markers in immunodiagnosis, immunoclassification and immunolocalization of gastrointestinal cancer. PMID- 3084195 TI - [A tumor-associated antigen of cervical cancer]. AB - The tumour-associated antigen was identified with the aid of antisera obtained from rabbits immunized with 3 M KCl extract of pool human cervical carcinoma cells. The antigen was found in 92.5% specimens of human cervical squamous cell carcinoma, in 4.7% specimens of other localization of the tumours. The antigen was absent from sets of normal human tissues. The tumour-associated antigen was not identical with CEA, alpha-fetoprotein, SP1, EPA and lactoferrin and it was localized in cytoplasm of cervical carcinoma cells. PMID- 3084196 TI - [Prospects for using the cryogenic factor in the radiation therapy of tumors]. AB - Experimental studies with 640 mongrel male rats with transplants of Guerin carcinoma and DMBA-induced tumours were performed. Separate groups of animals were subjected to isolated effects of cryodestruction, radiation therapy with total doses of 60 or 30 Gy and combined cryoradiation treatment by different schedule. The study revealed that an enhanced efficiency of combined treatment is achieved essentially by a two-fold decrease in the total irradiation dose in combination with tumour focal cryodestruction. PMID- 3084197 TI - [Automatic quantification of SEP for continuous patient monitoring]. AB - Parameters presently used to analyse evoked potentials such as amplitude and latency are based on well defined single components, the recognition of which may become arbitrary in severely altered responses. Furthermore, they ignore changes also present in the remainder of an evoked potential wave form. Hence, they are ill suited for monitoring comatose patients or patients during high risk surgery. Alternatively, crosscorrelation analysis may be employed yielding two parameters by comparing the SEP of the patient with a reference response: R, the correlation coefficient, a numerical measure of similarity of the two responses in terms of overall configuration and tau, indicating the time displacement of the main common components of the two signals. A "grand average" evoked potential (SEP) composed of the responses of age and sex matched healthy subjects or in perioperative monitoring the patient's own preoperative response might be used as a reference. By help of continuous averaging of the SEP these two parameters may be determined in real time allowing a more dynamic way of monitoring than by sequential averaging individual responses. PMID- 3084198 TI - [Conduction velocity and relative refractory period of the sural nerve in patients treated with ergot alkaloids]. AB - Relative refractory period and sural nerve conduction velocity were estimated in 30 probands and 52 patients treated with ergotamine tartrate using surface electrodes. A significant reduction in sural nerve relative refractory period could be correlated to an ergotamine dosage limited within therapeutical range. Patients under treatment without complaints even had a significant shorter relative refractory period compared to patients suffering from dysesthesia (p less than 0.01). Sural nerve conduction velocity showed a similar but not significant change in the tested patients. PMID- 3084199 TI - [Data display and reduction in computer-assisted EEG analysis in the time domain]. AB - Analysis of EEG frequency spectra leads in two fields to problems demanding optimal data reduction methods: especially if topological aspects have to be considered, it is likely that the rather limited memory capacity of laboratory computer systems will be exceeded; furthermore severe methodological problems arise in statistical analysis of combined data sets, including frequency spectra, other physiological, and non-physiological data. Three data reduction methods are discussed: the classification with respect to frequency bands, the search for prominent frequencies, and the computation of quartiles of the frequency spectra. There is some evidence in favour of the method of prominent frequencies. This method seems to preserve much of the differential information of the frequency spectra. PMID- 3084200 TI - [EEG changes in disseminated encephalomyelitis in comparison with the findings of cerebral magnetic resonance tomography]. AB - The electroencephalograms of 40 patients with acute symptoms of multiple sclerosis, 10 of whom presented with primary manifestation, were compared with the findings in cerebral nuclear magnetic resonance imaging. 32.5% of the patients EEGs showed abnormalities. Considering borderline findings the percentage of remarkable EEGs mounted to 60%. All of the patients presented periventricular lesions in NMR. In addition to the periventricular abnormalities between 1 and 26 district lesions per patient were found (mean = 6.5; Median = 5). In the patients group with five and more non-periventricular lesions, there were significantly more pathologic EEG-findings (p less than 0.05) than in the group with fewer lesions. Statistical correlations between EEG-abnormalities and the extent of functional deficit could not be substantiated. Neither could type and locality of EEG-changes be correlated to non-periventricular lesions in NMR. PMID- 3084201 TI - [Tifluadom, a benzodiazepine with opioid-like activity: study of its central mechanism of action in conscious dogs]. AB - A derivative of the 1,4-benzodiazepine series with reported opioid activity was evaluated in regard to its effect on central nervous activity in the awake canine. Additionally a possible benzodiazepine- or opioid-receptor interaction was evaluated by using specific antagonists. In 10 experiments increasing doses of tifluadom (5, 10, 20, 40, 80 micrograms/kg) modified somato-sensory-evoked potentials (SEP) inducing a dose-related latency change (40-80 micrograms/kg) and a suppression (80 micrograms/kg) of the P50-peak. Both effects are interpreted as a modification of stimuli reaching the somatosensory cortex. EEG-spectral analysis was characterized by a dose-related decrease of power in the higher frequency range (13-40 Hz) accompanied by an increase of power in the lower band (0.5-3.5 Hz). This effect was paralleled by deep sedation. The specific benzodiazepine antagonist Ro 15-1788 (240 micrograms/kg) was ineffective in reversing central nervous EEG- and SEP-changes. Naloxone (20 micrograms/kg) induced a short-term (5 min) arousal and a partial reversal of SEP-changes. The specific opioid-kappa-antagonist Mr 2266 (20 micrograms/kg) however, induced a long lasting return of power spectra and SEP-changes back to control. This results suggest that tifluadom, although being structurally a benzodiazepine, interacts with an opioid sub-receptor of the kappa-type, which is known to induce sedation and supraspinal analgesia without respiratory depression. PMID- 3084202 TI - [Nocturnal sleep studies of bruxism]. AB - Polygraphic recordings during two nights sleep in 7 selected outpatients prior to and following treatment of bruxism were carried out using EMG-, EEG and EOG recordings to evaluate the activities of the masseter muscle and the different sleep stages. The results thus obtained were compared to those of an age-matched control group. Following treatment with occlusal splints the recordings were repeated eleven weeks later. The length and the amount of grinding and pressing activities were correlated with the total night sleep as well as with the different sleep stages. The highest incidence of muscle activity was found in stage two and during awakening. Furthermore muscle activities were observed immediately before the beginning of REM-sleep and in particular during the change from REM- to NREM-sleep and in sleep stage one. After treatment with occlusal splints there was a decrease of total muscle activity, thus indicating efficiency of the treatment. PMID- 3084203 TI - [EEG changes in the withdrawal phase of tranquilizer or drug abuse]. AB - In 31 patients with tranquilizer-and 13 patients with drug abuse the character and extent of changes in EEG during withdrawal period were studied and the influence of additional abuse of alcohol or barbiturates was investigated. The EEG showed pathological results in 22 patients (50%). Generalised spike activity was dominant, which was found more often in patients with tranquilizer abuse (35%) than in patients with drug abuse (15%). In patients with abuse of tranquilizers and additional alcoholism pathological EEGs were found more often (65%) than in the remaining patients (36%). Also in patients with additional abuse of barbiturates pathological EEGs (67%) were found more often. In patients with drug abuse with or without additional abuse of alcohol or barbiturates there was no difference between the number of normal and pathological EEGs. In patients with longer persistence of the tranquilizer abuse the number of pathological EEGs increased. Controls of the EEG revealed with increasing time interval an increasing number of normalised EEGs especially in patients without alcoholism of barbiturate abuse. Therefore the EEG revealed functional disturbances in the withdrawal period after abuse of tranquilizers or drugs which were more pronounced in patients with additional abuse or alcohol or barbiturates. PMID- 3084204 TI - [Demonstration of an interpolation method for determining approximate maximum and minimum points as a prerequisite for EEG analysis in the time domain using computers with limited memory capacity]. AB - The EEG analysis in the time domain provides several advantages compared to the power spectra analysis, based on a FFT. There is the possibility to differentiate frequency, amplitude and other elementary characteristics of the wave form. This technique of EEG analysis is based on the definition of distinct characteristics of the wave form. Problems for calculating the frequency distribution arise- according to Harner, 1977--due to the fact, that the digitalization rate has to be very fast to reach an adequate resolution. On the other hand a high digitalization rate of 5 ms or below produces problems concerning the limited memory capacity of laboratory computers, especially if more than one derivation should be analysed simultaneously, to make further topological analyses possible. Three procedures of EEG analysis to calculate frequency distributions are shown, two of them are based on an interpolation technique to calculate adjusted minima maxima. The results of these procedures using two different digitalization rates, were compared and discussed to respect similarity of resulting frequency distributions. PMID- 3084205 TI - Arterial blood gases. AB - Blood gas determination provides physicians with detailed information regarding cardiopulmonary and metabolic homeostasis in the emergency patient. When integrated with the history and physical examination, the rapidly available arterial blood gas (ABG) analysis is useful in the resuscitation of the acutely ill or injured patient. This article discusses the physiology, analysis, and interpretation of ABG. PMID- 3084206 TI - Fetal plasma insulin and thyroid hormone levels during acute in utero ethanol exposure in a maternal-fetal sheep model. AB - The effects of acute in utero ethanol (ETOH) treatment on basal and stimulated thyroid and insulin levels in fetal plasma were studied in chronically cannulated fetal sheep. In test situations, pregnant ewes (0.78-0.88 gestation) which were chronically cannulated received 2 g/kg ETOH [25% (vol/vol) in isotonic saline] for 2 h; this was followed by a maintenance iv infusion of 0.13 g/kg ETOH. Control animals received isovolemic infusions of isotonic saline. Fetal arterial plasma samples were obtained after the 2-h infusion, and basal levels of T3, T4, glucose, and insulin were measured. The 2-h ETOH infusion did not influence fetal basal plasma T3, T4, insulin, or glucose. Fetal thyroid responses to an intraarterial injection of 0.01, 0.10, 1.00, or 10.00 micrograms/kg TRH or of 5 mU/kg TSH through the fetal catheters were studied in the presence or absence of high plasma ETOH concentrations. Fetal T4 or T3 levels during the 4 h following any of these stimuli were not significantly different in ethanol-treated and control animals. The effects of acute ETOH exposure on insulin responses to a glucose challenge were studied in six chronically cannulated ewes and their fetuses using a cross-over experimental design. After the 2-h ETOH infusion, ewes received a bolus injection of 600 mg/kg 50% glucose, followed by a 1-h infusion of 624 mg/kg 50% glucose and 0.13 g/kg ETOH. In control situations, ewes received saline plus glucose. Acute ETOH treatment did not influence maternal or fetal plasma glucose levels at any time, but enhanced both maternal and fetal insulin responses to glucose. Total insulin release, as measured by the area under the insulin response curve, was greater during ETOH exposure in both mother (ETOH, 4740 +/- 1475 microU/ml X min; control, 2807 +/- 766 microU/ml X min; P = 0.05) and fetus (ETOH, 562 +/- 94 microU/ml X min; control, 363 +/- 46 microU/ml X min; P less than 0.05). Thus acute in utero ETOH exposure does not diminish plasma levels of either thyroid hormones or insulin, two important hormones for fetal growth and development. However, ethanol exposure enhances the insulin response to increases in blood glucose in both mother and fetus. PMID- 3084208 TI - Oligosaccharide heterogeneity of insulin receptors. Comparison of N-linked glycosylation of insulin receptors in adipocytes and brain. AB - We tested the hypothesis that the molecular weight discrepancy between insulin receptors in brain and adipocytes is due to differences in glycosylation by treating photoaffinity-labeled insulin receptors from both tissues with endo-beta N-acetylglucosaminidase F (Endo F) and analyzing the products by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Endo F removed glycans from the adipocyte 125-kilodalton (kDa) subunit and the brain 115-kDa subunit in a manner dependent upon the concentration of enzyme and time of incubation. At a maximally effective concentration of Endo F, the adipocyte alpha-subunit was reduced from 125-kDa to 100-kDa and the brain alpha-subunit from 115-kDa to 100-kDa. We also examined the type of oligosaccharides present in both alpha-subunits by treating the proteins with endo-beta-N-acetylglucosaminidase H (Endo H), which selectively removes high mannose residues, and neuraminidase. Endo H treatment reduced the apparent molecular weight of both the adipocyte and brain alpha-subunits. In both receptors, the deglycosylated product obtained with Endo H was larger than that generated by Endo F. The adipocyte alpha-subunit demonstrated a shift in mobility on sodium dodecyl sulfate gels after neuraminidase treatment, whereas the brain alpha-subunit did not. We conclude from these studies that 1) The discrepancy in apparent molecular weight of alpha-subunits in brain and adipocytes is due to differences in N-linked glycosylation; 2) high mannose and complex type oligosaccharides are present in both receptor types; and 3) the complex oligosaccharides in the adipocyte alpha-subunit are terminated in a manner different from the complex glycans of the brain alpha-subunit. PMID- 3084207 TI - Effects of castration and testosterone administration on serum lipoproteins and their apoproteins in male spontaneously hypertensive rat. AB - Serum triglyceride and very low density lipoprotein (VLDL) concentrations were higher in male spontaneously hypertensive rat than in male control Wistar Kyoto rat, whereas serum cholesterol, phospholipids, and high density lipoprotein (HDL) concentrations were lower. Castration of hypertensive rats induced an increase in serum cholesterol, phospholipids, and HDL, and a decrease in serum triglyceride and VLDL. The cholesterol content of HDL increased, whereas the triglycerides decreased after gonadectomy of hypertensive rats. These changes in serum lipids and lipoproteins could be reversed by the administration of testosterone. Apolipoprotein E contents in VLDL and HDL of hypertensive rats were low when compared with control rats but rose after castration and could be reduced by testosterone administration. Hypertensive rats accumulated triglycerides and cholesterol in the liver, which resulted in an increase of liver weight. Castration reduced the hepatic lipids as well as liver weight. The effects of castration and testosterone treatment on lipids and lipoproteins were more prominent in spontaneously hypertensive rats than in control rats. These results suggest that testosterone reduces VLDL catabolism which is related to changes of apolipoprotein composition, and that hypertensive rats are more sensitive to testosterone than control rats. PMID- 3084209 TI - Polyamines in 1 alpha, 25-dihydroxycholecalciferol-induced differentiation of human promyelocytic leukemia cells, HL-60. AB - The human promyelocytic leukemia cell line, HL-60, differentiated into macrophage/monocytes in the presence of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3], as assessed by the percentage of morphologically mature cells and their ability to reduce nitroblue tetrazolium. In this study of the mechanism involved, the activities of ornithine decarboxylase and spermidine/spermine-N1 acetyltransferase (SAT), the rate-limiting enzymes of polyamine metabolism, as well as the cellular levels of polyamine were measured. ODC activity reached a peak 24 h after the addition of 1 alpha,25(OH)2D3 and then decreased, while SAT activity gradually increased as differentiation commenced. An increase in putrescine and decreases in spermidine and spermine were also observed. Addition of alpha-difluoromethylornithine, an irreversible inhibitor of ODC, with or without methylglyoxalbis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, caused no effect on 1 alpha,25(OH)2D3-induced cell differentiation, although the cellular levels of putrescine and spermidine decreased markedly. Addition of alpha-difluoromethylornithine markedly suppressed cell proliferation; this effect was reversed by the addition of exogenous putrescine. Addition of exogenous spermidine or spermine to overcome activation of SAT also had no effect on 1 alpha,25(OH)2D3-induced cell differentiation. These results suggest both that polyamine metabolism is not important in 1 alpha,25(OH)2D3-induced differentiation of HL-60 cells, but that it is intimately involved in the proliferation of these cells. PMID- 3084210 TI - Growth hormone (GH)-releasing factor stimulates hypothalamic somatostatin release: an inhibitory feedback effect on GH secretion. AB - GH-releasing factor (GRF) is a hypothalamic peptide that stimulates the secretion of pituitary GH. The possibility of feedback effects of GRF within the central nervous system was studied in conscious freely moving male rats with indwelling iv and intracerebroventricular (icv) cannulae. Animals were injected icv or iv with 10 ng-10 micrograms human (h) GRF(1-40)-OH (hGRF-40) or GRF(1-44)-NH2 (hGRF 44), and blood samples were obtained every 10-20 min from 1000-1400 h. GH secretion was pulsatile, with major secretory peaks at around 1200 h in most control animals. When 10 ng hGRF-40 were injected icv at 1100 h, immediately before the expected onset of the spontaneous GH secretory burst, GH secretion was suppressed during the following 2-h period. An iv injection of 10 ng hGRF-40 was without effect. In contrast, when 1 microgram hGRF-40 was injected icv or iv, plasma GH levels peaked at 20 and 10 min, respectively, and returned toward baseline shortly thereafter. The spontaneous GH secretory pulse after 1 microgram hGRF-40 (icv or iv) was suppressed in proportion to the magnitude of the GH secretory response to GRF (r = 0.78, p less than 0.01), and the prolongation of the interval between the injection of GRF and the subsequent spontaneous GH surge was directly related to the GH response to GRF (r = 0.85, p less than 0.001). The icv or iv injection of a larger dose of either hGRF-40 or hGRF-44 (10 micrograms) at 1100 h also resulted in marked and comparable increases in plasma GH levels, with peaks at 20 min (icv) and 10 min (iv) after injection. No changes in behavior or plasma glucose were observed up to 3 h after icv injection of any of the doses of hGRF-40 or of hGRF-44. The suppressive effect of centrally administered hGRF-40 (10 ng) on GH secretion was blocked by the iv administration of a specific antisomatostatin serum immediately before the injection of hGRF. These results demonstrate a dual action of GRF on spontaneous GH secretion and indicate the presence of an inhibitory feedback system within the central nervous system for the regulation of GH secretion which is mediated by hypothalamic somatostatin. PMID- 3084211 TI - Purified chicken growth hormone (GH) and a human pancreatic GH-releasing hormone increase body weight gain in chickens. AB - Purified chicken GH (cGH) and a synthetic human GH-releasing hormone (hpGRF) were tested for the ability to improve growth performance in chickens. Purified cGH was given to 4-week-old cockerels at 5, 10, and 50 micrograms/day for 14 days via daily iv injection. Body weights of chickens receiving 5 and 10 micrograms/day cGH were significantly increased at 6 days by 13.5% and 11.2%, respectively, relative to control values. At 14 days, body weights averaged 8.1% and 7.7% greater than controls, but these values were not statistically significant. There was a slight stimulation of body weight gain in chickens receiving 50 micrograms/day cGH. In general, cGH produces a transient stimulation of body weight gain in chickens. hpGRF was also given to 4-week-old cockerels for 14 days via daily iv injection at 0.1, 1.0, and 10.0 micrograms/day. hpGRF at 0.1 microgram/bird daily increased body weight on day 14 (9.1% over the control value). The stimulating effects of hpGRF on body weight are also transient. The effects of cGH on serum somatomedin-C (SM-C) were examined. Serum SM-C concentrations were significantly elevated 24 and 36 h after injection of cGH. In conclusion, purified cGH and hpGRF appear to have some growth-promoting activity. The stimulatory effect of hpGRF on weight gain may be mediated via GH, and the stimulatory effect of cGH could be mediated through SM-C. PMID- 3084212 TI - Subpopulations of lactotropes detected with the reverse hemolytic plaque assay show differential responsiveness to dopamine. AB - Cultured adenohypophysial cells secreting PRL were detected with a reverse hemolytic plaque assay. In this assay, PRL secretion from a pituitary cell results in hemolysis of cocultured protein A-coupled ovine erythrocytes in the presence of PRL antiserum and complement, so that a zone of hemolysis (a plaque) surrounds each lactotrope. The extent of hemolysis was related to the amount of PRL secreted by each lactotrope: batches of cohort cells incubated under similar conditions either in petri dishes for measurement of PRL secretion by RIA or in Cunningham chambers for measurement of plaque area revealed a significant relationship between secreted PRL and plaque area (r = 0.97; regression coefficient = 0.0007 pg/micron2). Measurement of plaque area on lactotropes derived from proestrous rats revealed a bimodal frequency distribution that was composed of cells forming small plaques (35% of the total lactotrope population) and others forming large plaques (65%). Treatment with 10(-7) M dopamine appeared to preferentially inhibit the large plaques; they decreased to 42% of the total with corresponding increases in the number of small plaques, but the total number of secretory lactotropes did not change. At 10(-5) M dopamine, large plaques virtually disappeared (only 9% remained), and small plaques appeared in increased numbers, but the number of secretory lactotropes decreased by about one third. These results suggest that the reverse hemolytic plaque assay can be used to quantify PRL secretion by individual lactotropes, that lactotropes from proestrous rats exist as two secretory subpopulations, and that dopamine may preferentially suppress the subpopulation secreting large amounts of PRL. PMID- 3084213 TI - Regulation of thyrotropin (TSH) bioactivity by TSH-releasing hormone and thyroid hormone. AB - The regulation of TSH biological activity by thyroid hormone and TRH was studied by comparison of pituitary and in vitro secreted TSH from normal and thyroidectomized rats that were alternatively treated with TRH either in vivo or in vitro. Normal and thyroidectomized (3 weeks postthyroidectomy), rats were injected with saline or TRH (100 micrograms) three times over 24 h. Pituitaries were incubated in vitro for 6 h, and six groups of samples from both pituitary and secreted TSH were analyzed: normal (n = 6), thyroidectomized (n = 6), normal and thyroidectomized groups treated with TRH in vitro (n = 2 each) with 10(-8) M TRH added to the incubation medium, and normal and thyroidectomized groups TRH treated in vivo, their incubation medium also supplemented with 10(-8) M TRH (n = 4 each). The biological activity of TSH in pituitary extracts and media was analyzed in terms of the ability to stimulate adenylate cyclase in human thyroid membranes. Thyroidectomy significantly decreased pituitary TSH bioactivity (70%) compared to normal, with no effect on secreted TSH in the medium. TRH, both in vivo and in vitro, when compared to the corresponding untreated groups, produced a significant increase in bioactive TSH in media from both normal (TRH in vivo, 131%; TRH in vitro, 139%) and thyroidectomized samples after TRH in vivo (158%). The TRH effect in the pituitary showed a significant increase in TSH bioactivity from normal samples treated with TRH in vivo (137%), whereas in thyroidectomized pituitary samples with TRH in vitro, TSH bioactivity was decreased (69%). These results indicate that thyroid hormone deficiency and TRH differentially regulate TSH bioactivity. Thyroid hormone deficiency induced a decrease in pituitary TSH bioactivity and favored the effect of TRH on secretion of more bioactive forms. TRH not only induced the formation of more bioactive forms but also stimulated their secretion into the medium. PMID- 3084214 TI - Control of gonadotropin secretion in the male during puberty: a decrease in response to steroid inhibitory feedback in the absence of an increase in steroid independent drive in the sheep. AB - The gonadostat hypothesis, i.e. that a decrease in response to the inhibitory feedback action of gonadal steroids occurs during puberty, was tested in the male lamb. Also investigated was whether a simultaneous steroid-independent rise in gonadotropin secretion could be the underlying mechanism for the reduction in steroid feedback sensitivity during puberty. Sexual maturation in intact Suffolk lambs was characterized by increases in all of the following parameters: Serum FSH and LH and LH pulse frequency (during 4-7 weeks of age), testicular size and testosterone (T) concentrations (during 7-28 weeks of age). Estradiol (E2) levels were elevated at 32 weeks. Motile spermatozoa were produced by 16-18 weeks of age. Castration at 5 weeks of age resulted in a prompt increase in gonadotropin concentrations. LH pulse frequency reached a plateau of approximately 5 pulses/4 h (n = 5) at 7 weeks of age and did not change thereafter. T or E2 replacement suppressed pulsatile LH secretion for several weeks. However, despite maintenance of constant serum T (approximately 1.0 ng/ml) or E2 (3-5 pg/ml) concentrations, LH pulse frequency began to increase after 9 weeks of age, and by 13 weeks, pulsatile secretion was apparent in all steroid-replaced castrated lambs. This was well after LH pulse frequency had ceased to increase in untreated castrated animals. These data support the gonadostat hypothesis for puberty in the male lamb. Furthermore, the temporal dissociation of increasing LH secretion in untreated castrated lambs and steroid-replaced castrated lambs suggests that a steroid-independent increase in gonadotropin secretion is not the mechanism underlying the decrease in responsiveness to steroid negative feedback. PMID- 3084215 TI - Immunological similarity between the insulin receptor and the protein encoded by the src oncogene. AB - Insulin receptors resemble receptors for certain growth factors (epidermal growth factor, platelet-derived growth factor, and insulin-like growth factor I) in that all possess tyrosine-specific protein kinase activity. These cell surface receptors resemble protein kinases encoded by viral oncogenes in that both groups of enzymes phosphorylate proteins on tyrosine. Recently, we reported that there is immunological similarity between the insulin receptor and pp60src [the protein encoded by the src oncogene of Rous sarcoma virus (RSV)]. This is supported by the observation that anti-pp60src antiserum (TBR serum) immunoprecipitated radiolabeled insulin receptors derived from cultured human cells (IM-9 lymphoblasts and U-937 monocytes) and rabbit liver. Moreover, highly purified preparations of src protein inhibit the immunoprecipitation of insulin receptors by TBR serum, and the inhibition is correlated with the src kinase activity present in the preparation used. However, two observations suggested that there were immunological differences between pp60src and mammalian insulin receptors. 1) Even at a relatively high concentration (dilution, 1:10), TBR serum immunoprecipitated a relatively small percentage (approximately 20%) of the labeled insulin receptors. 2) Some lots of TBR serum with a high titer against pp60src failed to immunoprecipitate the insulin receptor. Viral oncogenes are thought to have been derived from proto-oncogenes in the host cell. Therefore, because the chicken is the natural host for RSV, we inquired whether there might be closer homology between pp60src and avian insulin receptors. Surprisingly, under conditions where TBR serum immunoprecipitates human insulin receptors, we could not detect immunoprecipitation of avian insulin receptors from chicken liver, chicken embryo fibroblasts, or turkey erythrocytes. The immunoprecipitation of human insulin receptor is not dependent on the method used for labeling the cells ([125I]insulin cross-linking), inasmuch as the receptor labeled by autophosphorylation with [gamma-32P]ATP could also be immunoprecipitated by TBR serum. These observations suggest that there is structural homology between pp60src and the insulin receptor (most likely the beta-subunit). Nevertheless, it seems unlikely that the insulin receptor gene is the proto-oncogene for the src gene of RSV. PMID- 3084216 TI - Purification and partial characterization of a novel thyroxine-binding protein (27K protein) from human plasma. AB - T4-binding globulin (TBG) prepared from human plasma by the standard three-step procedure (T4-agarose affinity chromatography, anion exchange chromatography, and gel filtration) often shows in sodium dodecyl sulfate-polyacrylamide gel electrophoresis in addition to the expected 54K band, another with a mol wt of 27,000 (27K protein). The two proteins can be separated after the three-step procedure by chromatofocusing (because of different isoelectric points, 4.2-4.8 for TBG and 5.0-5.2 for 27K protein) or by T4-aragose chromatography eluting with a linear gradient of T4 (TBG is eluted between 10(-10) and 10(-9) M T4, 27K protein between 10(-8) and 10(-7) M T4). The 27K protein does not appear to be a fragment of TBG since 1) it does not displace [125I]TBG bound to anti-TBG monoclonal antibodies; and 2) absorption of polyclonal antibody reacting with both TBG and 27K protein with sera from TBG-deficient patients completely prevents [125I]27K protein binding, while only slightly affecting [125I]TBG binding. On the other hand, 27K protein is not simply a contaminant devoid of biological activity, but is a T4-binding protein, as supported by the following findings: 1) it covalently binds [125I]T4 by photoaffinity labeling, and this binding can be almost completely prevented by excess T4; 2) equilibrium dialysis shows two equivalent T4-binding sites per 66K, with an association constant of 0.85 X 10(7) M-1, intermediate between albumin and prealbumin; and 3) tryptophanyl fluorescence analysis shows quenching of 37% of the fluorescence when the protein is titrated with T4. The 27K protein appears as a single 27K band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, pH 8.8, but under nondenaturing nonreducing conditions mostly remains at the origin of the gel; a fraction enters the gel and migrates slightly ahead of albumin. This electrophoretic pattern is distinct from those of albumin, prealbumin, and TBG. In immunoelectrophoresis in agar at pH 8.6, 27K protein moves slightly faster than TBG. The results of equilibrium sedimentation indicate a mol wt of 66,000, suggesting that the 27K protein might exist as a dimer. These data indicate that the 27K protein is a previously unrecognized T4-binding protein with a low affinity for the hormone. Further studies are required to clarify its physiological role in the transport of circulating thyroid hormones. PMID- 3084217 TI - Estradiol secretion by granulosa cells from rats with four- or five-day estrous cycles: the development of responses to follicle-stimulating hormone versus luteinizing hormone. AB - The relative importance of LH vs. FSH in stimulating estradiol secretion by granulosa cells during follicular development was assessed in Sprague-Dawley rats with regular 4- or 5-day estrous cycles. At various times during diestrus (D-1200 h, D-2000 h) and proestrus (P-0800 h, P-1400 h, P-2000 h) granulosa cells were isolated from the presumptive preovulatory follicles. The cells were cultured with 0.5 microM testosterone and various doses of LH or FSH (0, 0.1, 1, 10, or 100 ng/ml). Media were collected and replaced daily for 3 days and measured for estradiol by RIA. Estradiol secretion in the absence of gonadotropins (endogenous aromatase activity) increased progressively with stage of the cycle. At earlier times of cell isolation (D-1200, D-2000, P-0800) secretion by cells from 5-day rats was greater relative to 4-day rats. Since estradiol production in the absence of gonadotropins declined progressively over each 3-day culture period, effects of the gonadotropins were most evident on the third day of culture when endogenous aromatase activity was low. On this day FSH consistently increased estradiol secretion above control levels. Sensitivity to FSH, as measured by the 50% maximally effective dose (ED50; approximately 1-3 ng FSH/ml), did not vary with cycle type or stage of the cycle and the response to FSH, in terms of 50% maximal estradiol secretion, was also relatively constant. In contrast, the effects of LH varied with cycle type and time of cell isolation. As follicles developed, cells from both 4- and 5-day rats became more sensitive to LH, as evidenced by a decline in the ED50 from approximately 32 ng LH/ml to approximately 3 ng/ml. This increase in sensitivity to LH is consistent with previous reports that the number of LH receptors on granulosa cells increases progressively during the final stages of follicular development. However, the increase in sensitivity to LH occurred earlier in cells from 5-day rats, relative to the expected next estrus (later, relative to the preceding estrus). Responsiveness to LH (50% maximal estradiol production) was relatively constant, except that it was lower in cells from 4-day rats isolated at D-1200. These results indicate that the LH receptors acquired by granulosa cells during diestrus and proestrus are functionally linked with aromatase activity and may, therefore, be important to the production of estradiol levels sufficient to elicit the LH surge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3084218 TI - Progesterone secretion by granulosa cells from rats with four- or five-day estrous cycles: the development of responses to follicle-stimulating hormone, luteinizing hormone, and testosterone. AB - Changes in granulosa cell sensitivity and responsiveness to gonadotropins during the rat estrous cycle were studied by measuring progesterone (P) secretion in vitro in response to treatment with increasing doses of LH or FSH (0, 0.1, 1, 10, 100 ng/ml). The effect of testosterone [(T); 0.5 microM] on response to gonadotropins was also examined. Granulosa cells were isolated from the largest ovarian follicles of rats with 4- and 5-day estrous cycles at 0800 h, 1400 h, and 2000 h on proestrus and on the preceding day of diestrus at 1200 h and 2000 h. In rats with 5-day cycles, granulosa cells were also obtained at 1200 h on the first day of diestrus. Fifty percent maximal P production and 50% effective dose (ED50 dose of gonadotropin which elicited 50% maximal P production) were calculated from dose-response curves for LH and FSH and were used as measures of responsivity and sensitivity to gonadotropins, respectively. Basal P secretion and 50% maximal P secretion increased progressively as cells were isolated at later stages of follicular growth in both 4- and 5-day cycles. In cells from 5 day rats, however, basal and gonadotropin-stimulated P secretion were higher on the second day of diestrus than in cells from 4-day rats. By proestrus responsiveness was equal. Granulosa cell sensitivity to FSH was constant during 4 and 5-day cycles, as indicated by a lack of change in the ED50. Granulosa cell sensitivity to LH was lower than sensitivity to FSH on diestrus of both 4- and 5 day cycles. However, by the morning of proestrus sensitivity to LH increased and was similar to that for FSH. T increased basal P production only slightly, but synergized with both LH and FSH to stimulate 2-fold increases in 50% maximal P production by granulosa cells isolated at all times except 2000 h on proestrus, after the endogenous LH surge. T had no effect on the sensitivity (ED50) of granulosa cells to LH or FSH. In summary, granulosa cell responsiveness to LH and FSH increased in parallel during the final stages of follicular growth, but increased sensitivity was noted only for LH. The development of granulosa cell capacity to secrete P appears to be more advanced in 5-day rats than in 4-day rats relative to the next estrus. Because T synergized with LH and FSH to increase P secretion without altering sensitivity to gonadotropins, it probably acts at a site distal to gonadotropin receptors. PMID- 3084219 TI - The effects of anterior hypothalamic deafferentation on thyrotropin (TSH) biosynthesis and response to TSH-releasing hormone. AB - The effects of hypothalamic deafferentation on TSH synthesis were studied by making cuts of 180 degrees arc in the anterior hypothalamus (n = 18) or sham cuts (n = 12) in rats. After 21 days, pituitaries were incubated with [35S]methionine (MET), [3H]glucosamine (GLCN), with or without 10(-8)M TRH for 24 h. TSH and free alpha-subunits were immunoprecipitated and analyzed by gel electrophoresis. In the deafferented group as compared to sham, MET incorporation into both subunits of secreted TSH was decreased (alpha, 96 +/- (SE) 9 X 10(3) vs. 180 +/- 20 X 10(3) dpm/mg protein; beta, 35 +/- 9 X 10(3) vs. 84 +/- 15 X 10(3) dpm/mg protein; P less than 0.05). Basal GLCN incorporation into both subunits of secreted TSH was also decreased in the deafferented group (alpha, 6.5 +/- 11 X 10(3) vs. 132 +/- 17 X 10(3) dpm/mg protein; beta, 36 +/- 8 X 10(3) vs. 101 +/- 29 X 10(3), P less than 0.05). In vitro TRH did not stimulate MET incorporation into secreted TSH in the sham controls but did in the deafferented group (alpha, 270% of basal; beta, 374% of basal; P less than 0.01). In vitro TRH increased GLCN incorporation in secreted TSH in both the sham (alpha, 253% of basal; beta, 245% of basal; P less than 0.02) and the deafferented group (alpha, 692% of basal; beta, 630% of basal; P less than 0.01). GLCN/MET ratio, reflecting relative glycosylation, did not differ for sham or deafferented groups but increased 2-fold with in vitro TRH in each group for both secreted subunits (P less than 0.01). Free alpha-synthesis and intrapituitary TSH were not altered by deafferentation or TRH. In summary, 1) anterior hypothalamic deafferentation decreases basal TSH protein and carbohydrate synthesis; 2) such deafferentation increases sensitivity to TRH stimulation of TSH synthesis, most notably apoprotein synthesis; 3) TRH increases relative glycosylation of secreted TSH in both deafferented and sham groups. These data suggest that TRH plays a significant role in regulating basal TSH protein and carbohydrate synthesis, glycosylation of TSH subunits, and subsequent bioactivity. PMID- 3084220 TI - Decreased serum 3,5,3'-triiodothyronine (T3) and abnormal serum binding of T3 in calorie-deficient rats: adaptation after chronic underfeeding. AB - Both starvation and feeding of a low protein diet have dramatic effects on serum thyroid hormone concentrations and on the serum binding proteins for thyroid hormones in rats. We examined whether similar changes might be seen in another model of undernutrition, namely underfeeding without alteration of dietary composition, and in particular whether such changes would disappear after prolonged alteration in diet (adaptation). Male rats aged 21 days were put on five different levels of intake of a diet of normal composition (18% protein, 70% carbohydrate), and animals from each dietary group (n = 8-10) were killed after 30, 60, or 100 days of underfeeding. After 30 or 60 days of underfeeding, significant direct correlations were observed between growth rate (used as an index of the degree of underfeeding) and serum T3 (RIA), percent free T3 (equilibrium dialysis), and serum free T3 (T3 X percent free T3). When underfeeding was prolonged to 100 days, however, there was no correlation between growth rate and percent free T3, while the correlation between growth rate and serum free T3 was weak (r = 0.33). Qualitatively similar changes were seen when animals given five different levels of food intake were killed at three body weight milestones rather than three separate age milestones. Polyacrylamide gel electrophoresis of serum thyroid-binding proteins revealed that the low percent free T3 in underfed rats seen after 60 days of underfeeding was associated with the development of a thyroid-binding globulin not normally found, but this had disappeared by 100 days of underfeeding. We conclude that nutrition-related changes in serum thyroid hormone variables show adaptation over time. Because of changes in serum binding of thyroid hormones caused by undernutrition, total serum thyroid hormone concentrations may not be an accurate reflection of thyroid status in any investigational study in which an experimental treatment leads to decreased food intake. PMID- 3084221 TI - Mineralocorticoid activity of 19-hydroxyaldosterone, 19-nor-aldosterone, and 3 beta-hydroxy-delta 5-aldosterone: relative potencies measured in two bioassay systems. AB - The mineralocorticoid (MC) activities of 19-hydroxyaldosterone (19-OH-Aldo) and 19-nor-aldosterone (19-nor-Aldo) were tested in adrenalectomized male rats. Potency was assessed by three criteria. Overall MC activity is expressed as the ability to decrease the urinary Na+ to K+ ratio; antinatriuretic activity is represented by decreases in the urinary Na+ to creatinine ratio, and kaliuretic activity by increases in the K+ to creatinine ratio. All measurements were made on urine collected 1-3 h postinjection. In this assay, 19-OH-Aldo was 1/100th to 1/140th as active as Aldo, and 19-nor-Aldo possessed MC activity similar to that of Aldo; both steroids possessed antinatriuretic and kaliuretic activities. In contrast, when assayed in vitro in the isolated toad urinary bladder, the natriferic responses of both 19-OH-Aldo and 19-nor-Aldo (10(-8), 10(-7), and 10( 6) M) were not significantly different from those caused by equivalent concentrations of Aldo. 3 beta-Hydroxy-delta 5-Aldo is active as a MC in the adrenalectomized male rat, being 1/20th to 1/35th as active as Aldo, but, in contrast to 19-OH-Aldo, was less active in the isolated toad bladder system. 19 OH-Aldo, 19-nor-Aldo, and 3 beta-hydroxy-delta 5-Aldo could represent important new classes of Aldo analogs. PMID- 3084222 TI - Episodic patterns of luteinizing hormone and follicle-stimulating hormone release: differential secretory dynamics and adrenergic control in ovariectomized rats. AB - Long term (4 weeks) ovariectomized rats were bled sequentially at 5-min intervals for 5 h via indwelling intraatrial cannulas. Plasma LH and FSH secretory patterns were determined from the same plasma samples by RIA. Hormonal profiles were subjected to power spectral analysis to determine periodicities of plasma LH and FSH. Distinct and regular release patterns were observed for LH, with significant periodicities between 20-40 min. In contrast to LH, FSH oscillations were neither as distinct nor as regular. However, significant periodicities in FSH (50-60 min) were often detected. At times, plasma LH and FSH appeared to be synchronized, but there were numerous instances of differential secretion. The effects of intracerebroventricular infusion of norepinephine (NE) and clonidine (an alpha 2 agonist) were tested in another group of animals. After a 2- to 3-h control bleeding period each animal bearing a chronic third ventricle cannula received an intracerebroventricular infusion of 0.3 mumol NE, clonidine, or vehicle. Blood sampling was continued for 2-3 h after infusion. Intracerebroventricular infusion of NE caused rapid and potent inhibition of LH secretion with FSH affected to a lesser extent. NE infusion decreased mean plasma LH levels and LH pulse amplitude while causing a marked increase in pulse period. Although mean FSH levels declined after NE infusion, secretory episodes of FSH were detectable even in the absence of pulsatile LH secretion. Infusion of an equimolar dose of clonidine produced a biphasic response in LH, a transient elevation followed by a decrease in overall plasma levels. In contrast to LH, plasma FSH levels showed only a delayed decrease after clonidine infusion. No significant changes in pulse amplitude or pulse period for either gonadotropin were observed. These data show that plasma FSH, like LH, oscillates in a periodic manner, but when compared with episodic LH secretion there are both quantitative and qualitative differences. Although the neural mechanisms involved in periodic LH release are also involved to a lesser extent in FSH secretion, it appears that independent regulatory mechanisms exist for LH and FSH as well. PMID- 3084223 TI - Gonadotropin-releasing hormone-mediated desensitization of cultured rat anterior pituitary cells can be uncoupled from luteinizing hormone release. AB - GnRH stimulates LH release from pituitary gonadotropes. Prolonged exposure of these cells to GnRH results in decreased sensitivity to further stimulation by the releasing hormone both in vivo and in vitro. Chelation of extracellular Ca++ with EGTA blocks GnRH-stimulated LH release but does not prevent subsequent desensitization. Desensitization occurs when cells are preincubated in EGTA containing 10(-7) M GnRH for a variety of times (20 min to 12 h) or when cells are preincubated for 3 h in EGTA with 10(-10), 10(-9), or 10(-8) M GnRH. A GnRH antagonist does not cause desensitization to GnRH and blocks desensitization in response to GnRH in the Ca++-free medium. Preincubation in EGTA containing 10(-7) M GnRH for 3 h did not alter sensitivity of cells to sn 1,2 dioctanoylglycerol (a protein kinase C activator), Ca++ ionophore A23187, or veratridine (an activator of endogenous ion channels). These results suggest that desensitization results from occupancy of the GnRH receptor by an agonist and may be uncoupled from LH release. PMID- 3084224 TI - Cyclic ovarian function in a male macaque: additional evidence for a lack of sexual differentiation in the physiological mechanisms that regulate the cyclic release of gonadotropins in primates. AB - Ovarian tissue from adult female rhesus macaques was transplanted into sc abdominal pouches of 4 male rhesus macaques that had been castrated after reaching sexual maturity. The animals were treated daily with cyclosporin A to prevent rejection of the ovarian transplants. Two males in which the transplants were successful showed preovulatory-like gonadotropin surges in response to increasing levels of estradiol. In one of these males (7082), circulating levels of gonadotropins and steroids indicated that cyclic ovarian function had been established. This male showed 5 successive ovarian cycles that averaged 28 days in length. Comparison of the changes in reproductive hormones between 7082 and females with normal menstrual cycles support the hypothesis that the neuroendocrine mechanisms that regulate cyclic release of gonadotropins in primates are not sexually different. PMID- 3084226 TI - Progesterone secretion by primary cultures of rat luteal cells. AB - Primary cultures were prepared from ovaries of immature rats that had been superovulated. The dispersed luteal cells attached to growth surfaces, formed monolayers and secreted progesterone. Progesterone accumulation in the medium was most pronounced in the first week of culturing. Removal of serum from the medium resulted in a progressive decline in progesterone concentration in the culture medium which reached basal levels by 5 hours. In medium without serum, the addition of hCG, FSH or prolactin stimulated an increase in progesterone secretion within 1 hour. Also cholera toxin stimulated a significant increase in progesterone levels in the medium. Prior exposure of cultures to estradiol for 3 days did not augment the response to hCG and inhibited the ability of cholera toxin to stimulate progesterone secretion. These results indicate that the steroidogenic function of rat luteal cells can be studied in culture and that a number of hormones rapidly stimulate the secretion of progesterone from these cells. PMID- 3084225 TI - HLA-DR alpha chain expression in human thyroid cells. AB - Using a cDNA probe encoding the human major histocompatibility Class II antigen HLA-DR alpha chain, we have detected a single DR alpha chain-specific transcript in total cellular RNA prepared from human thyroid tissue. The hybridizable RNA in thyroid samples was indistinguishable in size from the DR mRNA in the Raji human B lymphoblastoid cell line. Of the thyroid glands examined, samples from patients with autoimmune thyroid disease consistently demonstrated the highest DR alpha chain transcript levels, with a mean +/- SEM OF 62 +/- 13% of levels found in DR positive Raji cells. Cytoplasmic dot blot analyses of 5-day thyroid cell cultures depleted of lymphocytes and monocytes indicated that normal thyrocytes contain readily-detectable levels of DR alpha chain-mRNA. These transcript levels varied from individual to individual, with a mean of 16 +/- 9% relative to Raji cell control values and were shown to correlate after lectin or gamma interferon stimulation with enhanced numbers of immunoreactive DR antigen-positive cells. Such findings demonstrate expression of HLA Class II antigen genes in normal unstimulated human thyroid cells and suggest that quantitative variation in thyroid Class II antigen (DR) gene expression may be a major factor in thyroid immunoregulation. PMID- 3084227 TI - Valproate reduces excitability by blockage of sodium and potassium conductance. AB - Effects of the antiepileptic drug valproate on sodium and potassium currents in the nodal membrane of peripheral nerve fibers of Xenopus laevis were determined by voltage- and current-clamp experiments. Under voltage-clamp conditions, a reduction of both sodium and potassium conductance (in a ratio of 2:1) was observed. Typically, 2.4 mM (400 mg/L) valproate reduced the sodium current 54% and the potassium current 26%, at a membrane potential of 5 mV. Valproate did not affect the leakage conductance. The reduction of potassium conductance was voltage dependent, being more pronounced at more positive membrane potentials. For the sodium system, a voltage dependency of the blockage could not be established. Under current-clamp conditions, valproate caused a reduction of excitability of nerve membrane: amplitude of the action potential and maximum rate of rise were decreased, whereas threshold potential was increased. The ability to follow high-frequency stimulation was impaired. PMID- 3084228 TI - Selective metabolic activation of the mammillary bodies and their connections during ethosuximide-induced suppression of pentylenetetrazol seizures. AB - Electroencephalographic (EEG) activity and regional [14C]2-deoxyglucose incorporation in brain were examined in guinea pigs treated with pentylenetetrazol (PTZ), ethosuximide (ESM), phenytoin (PHT), or combinations of these drugs. Convulsant doses of PTZ induced EEG epileptiform discharges in paralyzed and ventilated animals and resulted in a large increase in labeled glucose accumulation in essentially all brain areas. ESM alone depressed EEG activity and accumulation of label, whereas PHT alone had little or no effect. Autoradiographs of PTZ-infused animals pretreated with PHT, which facilitated the onset and increased the severity of the PTZ seizures, were similar to those of animals treated with convulsant alone, with additional label uptake in the globus pallidus and substantia nigra. Pretreatment of PTZ-infused animals with sufficient ESM to prevent most EEG spike activity reduced glucose incorporation in most brain regions, but increased it in some. Selective enhancement of label uptake was observed in the mammillary bodies, mammillothalamic tracts, the anterior nuclei of the thalamus, the mammillary peduncles, and the dorsal and ventral tegmental nuclei of the midbrain. These data suggest that the mammillary nuclei and their projections to the anterior thalamic nucleus and their reciprocal projections to and from the tegmental nuclei may be important in the mediation of seizure activity induced by PTZ and/or the anticonvulsant action of ESM. PMID- 3084229 TI - Effect of aminophylline on the protective action of common antiepileptic drugs against electroconvulsions in mice. AB - The increasing amount of data tends to suggest that adenosine-mediated inhibition may play a role in the anticonvulsant activity of a number of antiepileptic drugs. Consequently, we tried to reverse the protective action of acetazolamide [(40 and 80 mg/kg) i.p.; 60 min before the test]; carbamazepine (20 and 30 mg/kg i.p., 60 min); diazepam (5 and 10 mg/kg i.p., 60 min); diphenylhydantoin (8 and 12 mg/kg i.p., 120 min), phenobarbital (20 and 30 mg/kg i.p., 120 min) and valproate (200 and 300 mg/kg i.p., 30 min) with aminophylline (50 and 100 mg/kg i.p., 30 min) against electroconvulsions in mice. Aminophylline markedly decreased the anticonvulsant efficacy of almost all drugs studied, acetazolamide (40 and 80 mg/kg) and carbamazepine (30 mg/kg) being the only exceptions. The ethylenediamine component of aminophylline did not modify the anticonvulsant activity at all. These results seem to support the suggestion that aminophylline induced blockade of adenosine receptors might be involved in the reversal of the protective action of at least some drugs studied. Regardless of the nature of the aminophylline-induced impairment in the anticonvulsant efficacy of a number of antiepileptic drugs, the use of methylxanthines in epileptic patients for the treatment of obstructive lung diseases should be avoided. PMID- 3084230 TI - Differential antiepileptic sensitivity between cortical sites in the rat. AB - The relative efficacies of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and valproic acid (VPA) in the suppression of focal and generalized seizures produced by electrical stimulation of two different cortical sites (areas 3 and 10) were evaluated in the rat. The two cortical sites were distinguished by significantly different dose-response curve slopes for the suppression of afterdischarge duration by PHT, CBZ and VPA, which suggests more than one mechanism of action for these drugs. The dose-response curve slopes for PB, on the contrary, were not significantly different, although its potency was significantly greater in area 10. For suppression of generalized convulsions, dose-response curve slopes were not significantly different for any of the drugs. Potencies of PHT, CBZ and VPA were equivalent in the two areas, but PB was significantly more potent in the suppression of generalized convulsions triggered from area 10. It is concluded that focal seizures elicited by the stimulation of different cortical sites are differentially refractory to antiepileptic drugs. PMID- 3084231 TI - Reversible valproic acid-induced dementia: a case report. AB - Reversible valproic acid-induced dementia was documented in a 21-year-old man with epilepsy who had a 3-year history of insidious progressive decline in global cognitive abilities documented by serial neuropsychological studies. Repeat neuropsychological testing 7 weeks after discontinuation of the drug revealed dramatic improvement in IQ, memory, naming, and other tasks commensurate with clinical recovery in his intellectual capacity. Possible pathophysiological mechanisms which may have been operative in this case include: a direct central nervous system (CNS) toxic effect of valproic acid; a paradoxical epileptogenic effect secondary to the drug; and an indirect CNS toxic effect mediated through valproic acid-induced hyperammonemia. PMID- 3084232 TI - Partial epilepsy in neurologically normal children: clinical syndromes and prognosis. AB - A clinical and electroencephalographic study of 107 neurologically normal children with partial seizures was undertaken to verify the existence and determine the frequency of epileptic syndromes reported in selected populations. Sixty-three children had simple partial seizures, 39 had complex partial seizures, and 5 children were unclassifiable. The syndrome of benign partial epilepsy of children with rolandic spikes (BPEC, 38 cases) was clearly identified and its uniformly benign final prognosis was confirmed even if some of these children had at times severe or poorly controlled seizures. Among the children with simple partial seizures outside the BPEC (25 cases) and complex partial seizures (39 cases), no homogeneous clinical or electroclinical subgroup could be found. Two children with benign partial epilepsy and myoclonic-astatic seizures ("atypical benign partial epilepsy of childhood") and one child with "benign epilepsy with occipital spike-waves" were identified. 74% of children with epilepsy with complex partial seizures (ECP) had a 1-year seizure-free interval, and many children with epilepsy with simple partial seizures outside the BPEC group (ESP) had no more than two seizures. A benign course is thus not limited to the BPEC but is difficult to predict. Prospective studies are necessary to confirm the existence of well-defined benign syndromes among the idiopathic partial epilepsies of childhood, which appear quite rare outside the BPEC. PMID- 3084233 TI - A semiselective test for the detection of first- and second-division nondisjunction in Drosophila melanogaster. AB - Little is known about the relative frequency of induction of nondisjunction in the first and second divisions of meiosis. The killer of prune system is a semiselective Drosophila aneuploidy assay designed to detect chromosome gain resulting from first- or second-division nondisjunction in males. The system can also detect X-Y interchange. Extensive data from nonmutagenized controls indicate that all the expected phenotypes can be recovered. Spontaneous nondisjunction in the first division is three times more frequent than in the second division. Spontaneous interchange between the X chromosome and YS is six times more frequent than between the X chromosome and YL. Exposures of larval males to X rays, 35 degrees C heat shock, and colchicine were performed. X-ray exposure induced an increase in X-Y interchange events only. A 24-hr heat shock induced an increase in first-division nondisjunction and one type of interchange event. Colchicine failed to induce both nondisjunction and interchange, although it did decrease fertility. The Killer of prune test is of potential value because it allows for the assessment of the relative sensitivities of the two meiotic divisions to perturbations in chromosome number. PMID- 3084234 TI - Chromosome analysis of trifluorothymidine-resistant L5178Y mouse lymphoma cell colonies. AB - Cells from small (sigma) and large (lambda) trifluorothymidine-resistant (TFTr) colonies induced by chemical mutagen treatment of TK+/-L5178Y mouse lymphoma cells were examined for chromosomal abnormalities. Analysis of G-banded metaphase chromosomes from 34 sigma-TFTr colonies revealed that cells from 20 (59%) possessed one or more chromosomal abnormalities. The most frequent (16/20 colonies) abnormality observed in cells from sigma-TFTr colonies involved the addition of extra chromatin to the distal region of one chromosome number 11. In 13 of these 16 colonies, the origin of the chromatin translocated to chromosome number 11 could not be identified; the chromatin was not missing elsewhere in the genome. The remaining three sigma-TFTr colonies with an abnormal chromosome number 11 had apparently whole chromosomes translocated, in tandem, to the distal region of chromosome number 11. Chromosomal abnormalities observed in cells from sigma-TFTr colonies with normal number 11 chromosomes included 2N/4N and 2N/4N/8N mosaicism (two colonies), a Robertsonian translocation involving chromosome 10 and a marker chromosome (one colony), and trisomy 7 (one colony). In most (14/16) sigma-TFTr colonies with structural damage to chromosome number 11, the cells within a colony were heterogeneous in that some possessed chromosomal damage whereas others were apparently normal. Analysis of chromosomes in cells from eight lambda-TFTr colonies revealed one colony in which all cells had a Robertsonian translocation involving chromosomes 1 and 16 plus other structural abnormalities. The chromosomes of cells from the remaining lambda-TFTr colonies were apparently normal. PMID- 3084235 TI - Albumin and immunoglobulins G, A and M in aqueous humour from clinically normal equine eyes. AB - The levels of albumin, immunoglobulin G (including IgG [T]), IgA and IgM in the serum and aqueous humour of 47 horses and ponies with no ophthalmic abnormalities were determined by single radial immunodiffusion. There was a linear relationship between serum and aqueous albumin levels. No relationship of serum and aqueous IgG levels was observed. IgA was detected in only one aqueous sample. IgM was not detected in aqueous humour from any eye in this study. The factors which may influence albumin and immunoglobulin levels in normal aqueous humour are discussed. PMID- 3084236 TI - Schistosoma haematobium in Western Ethiopia. PMID- 3084237 TI - The influence of hyperventilation on the measurement of stroke volume using a CO2 rebreathing method. AB - The influence of different degrees of hyperventilation on stroke volume measured with a CO2 rebreathing method was studied in seven normal subjects and seven patients with aortic regurgitation. Hyperventilation was initially performed with a rebreathing rate of 30 min-1 and a tidal volume corresponding to 60% of the subject's vital capacity. The tidal volume was then randomly decreased or increased by 0.5 and 1.01 and the procedure was repeated with rebreathing rates of 25 and 35 min-1. The possible influence of habituation to repeated measurements was tested in seven of the subjects. No significant differences in response to hyperventilation of stroke volume, cardiac output or heart rate were found between normal subjects and patients. When the tidal volume was increased, there was a significant increase in heart rate and also an increase in cardiac output, which was significant when comparing measurements performed with the lowest and highest tidal volumes. When comparing initial and final measurements, there was a significant decrease in heart rate and a tendency to decrease in cardiac output. Stroke volume was not affected by variations in rebreathing rate from 25 to 35 min-1 or tidal volume changes of +/- 0.51 and was also unaffected by repeated measurements. PMID- 3084239 TI - Serum bactericidal activity of mezlocillin, ceftazidime, mezlocillin/ceftazidime and mezlocillin/amikacin against Klebsiella pneumoniae and Pseudomonas aeruginosa. AB - Sera of volunteers receiving 1 g mezlocillin, 5 g mezlocillin, 1 g ceftazidime, 3 g ceftazidime, 1 g mezlocillin plus 1 g ceftazidime, and 1 g mezlocillin plus 500 mg amikacin, respectively, were evaluated for bactericidal activity against clinical isolates of Klebsiella pneumoniae and Pseudomonas aeruginosa. The titers of bactericidal activity against Klebsiella pneumoniae in serum from subjects receiving ceftazidime were higher than with other regimens both one and six hours after administration. Peak titers of bactericidal activity greater than or equal to 1:8 were also achieved more often against Pseudomonas aeruginosa in sera from subjects receiving ceftazidime than with other regimens. Killing studies confirmed these results. Although the checkerboard technique indicated synergism with the combination mezlocillin plus amikacin in vitro, this was not confirmed in vivo. Single drug therapy with ceftazidime was superior to the tested combinations. PMID- 3084238 TI - Regulation of macrophage phagocytosis. AB - The removal of pathogens from the circulation is achieved primarily by cells of the mononuclear phagocyte system, also known as the reticuloendothelial system. The tissue macrophage is the most important component of this system. The phagocytic activity of macrophages is regulated by opsonins on pathogenic materials and by endogenous cytokines. A number of diseases are caused by qualitative or quantitative disorders of phagocytosis by four major mechanisms: a decrease in the flow of blood to organs which contain macrophages (e.g. congestive heart failure and portal hypertension); a decrease in the quantity of tissue which contains macrophages (e.g. hepatic cirrhosis and splenectomy); a decrease in the effective opsonization of pathogens because of a deficiency of complement or IgG; and qualitative dysfunction of macrophages due to a deficiency of regulatory cytokines (e.g. gamma interferon and tuftsin) or a direct inhibitory effect on the macrophage (e.g. viral infections). New approaches for selective regulation of the phagocytic activity of macrophages are emerging. PMID- 3084240 TI - Comparison of the serum bactericidal activity of ceftriaxone/piperacillin and ceftriaxone/netilmicin. AB - The serum bactericidal activities of ceftriaxone, netilmicin, piperacillin and the combinations of ceftriaxone with each of the two other antibiotics were compared 1, 4 and 24 h after i.v. infusion in six volunteers. One hundred and one clinical isolates were used, including Staphylococcus aureus, Pseudomonas aeruginosa and various Enterobacteriaceae. The highest bactericidal titers were found against the Enterobacteriaceae, geometric means of 1:741 and 1:851 being obtained for ceftriaxone/netilmicin and ceftriaxone/piperacillin respectively. Against Staphylococcus aureus the geometric mean bactericidal titers of ceftriaxone/piperacillin (1:105) were markedly higher than ceftriaxone/netilmicin (1:35). Low bactericidal activity was exhibited by all drugs and combinations tested against Pseudomonas aeruginosa; a geometric mean bactericidal titer of 1:4.6 was achieved. The serum bactericidal activity of the double beta-lactam combinations was found to be at least equal to that of the combination containing a cephalosporin and an aminoglycoside. PMID- 3084241 TI - Evaluation of novel antipseudomonal drugs using the serum bactericidal activity test. AB - Serum bactericidal activity against Pseudomonas aeruginosa was determined in six volunteers 1 and 4 h after administration of 2 g ceftazidime, 4 g piperacillin, 500 mg imipenem, 80 mg tobramycin and four combinations of these agents. Ceftazidime produced the highest serum bactericidal titers, killing 100% and 86% of the 50 Pseudomonas aeruginosa strains tested after 1 and 4 h respectively at a serum dilution of 1:8. Imipenem had lower serum bactericidal titers than ceftazidime, killing 88% of the isolates after 1 h at a serum dilution of 1:8. The combination showed only slightly higher titers. Killing curves were determined for nine strains of Pseudomonas aeruginosa using undiluted volunteer serum drawn 1 h after administration of the antibiotics. The combinations ceftazidime/tobramycin and piperacillin/tobramycin exhibited higher killing activity than the single drugs. As the activity of the aminoglycosides could be underestimated on the basis of their low serum bactericidal titers, it is concluded that determination of these titers is inappropriate for evaluating the efficacy of the aminoglycosides. PMID- 3084242 TI - Factors influencing the activity of the trometamol salt of fosfomycin. AB - The antibacterial activity of trometamol fosfomycin and its potentiation by glucose-6-phosphate were found to vary considerably in different culture media, although not all bacteria tested were equally affected. In general, the lowest MICs were obtained in the presence of glucose-6-phosphate in nutrient broth and Eugonbroth. The influence of inoculum size, pH and potentiation by glucose-6 phosphate were investigated by agar incorporation MIC titrations on nutrient agar. The activity of trometamol fosfomycin against many strains increased as the pH was lowered from 7.9 to 5.5. Only 9% of the strains showed an inoculum effect when tested at pH 5.5 in the presence of glucose-6-phosphate compared with 37% of the strains tested at pH 7.1 and 22% of the strains tested at pH 7.9. In the absence of glucose-6-phosphate, about 10% of the strains showed an inoculum effect at all three pH levels. The addition of glucose-6-phosphate to culture media seems reasonable for the testing of fosfomycin susceptibility. PMID- 3084243 TI - Catheter sepsis due to coagulase-negative staphylococci in patients on total parenteral nutrition. PMID- 3084244 TI - Dot-immunobinding assay with a monoclonal antibody for detection of group B meningococcal antigen. PMID- 3084245 TI - In vitro antimicrobial susceptibility of penicillinase-producing Neisseria gonorrhoeae in Japan. PMID- 3084246 TI - Serum bactericidal test in volunteers--a review. AB - A review is given of work utilizing the serum bactericidal test for preclinical evaluation of agents considered for treatment of gram-negative sepsis among neutropenic cancer patients. Following a description of the methodology of the two major groups, the results of the various antibiotic trials are summarized. First the extended-spectrum cephalosporins (cefotaxime, cefoperazone, and moxalactam) were tested and found to be, at best, of limited value as single agents for Pseudomonas aeruginosa, a common pathogen of neutropenic cancer patients. When the extended-spectrum penicillins became available, the serum bactericidal levels in volunteers of mezlocillin and piperacillin were compared alone or in combination with an aminoglycoside to ticarcillin with or without aminoglycoside against the same organisms. Piperacillin proved to be most effective followed by mezlocillin and then ticarcillin; in each case the addition of the aminoglycoside improved serum bactericidal activity. Recent studies suggest that imipenem alone is as active as the combination of a broad-spectrum penicillin plus an aminoglycoside and is worthy of a carefully controlled clinical trial. These types of volunteer-based evaluations of the serum bactericidal activity of new compounds may help predict useful clinical approaches for the future. PMID- 3084247 TI - Correlation of predicted serum bactericidal activities and values measured in volunteers. AB - A method was devised for predicting the serum bactericidal activity of new drugs. Six healthy volunteers received 2 g moxalactam, cefoperazone and cefotaxime, respectively, as 30-min infusions in a crossover manner at one-week intervals. The pharmacokinetics of each drug was characterized and the bactericidal activity of the serum 1 h after infusion was measured against panels of six strains of Pseudomonas aeruginosa, six strains of Escherichia coli, six strains of Staphylococcus aureus, and four strains of Klebsiella pneumoniae. The minimum bactericidal concentration of each antibiotic was determined for each organism by the standard NCCLS reference method and the method of Stratton and Reller. On the basis of these values and a serum concentration-time curve constructed from individual patient pharmacokinetic parameters, the bactericidal activity of the serum 1 h after infusion was predicted. These predictions showed a 90% agreement with measured values calculated according to the method of Stratton and Reller, whereas an agreement of 74% was obtained with the reference method. This difference was statistically significant (p less than 0.001). PMID- 3084248 TI - Effect of increasing doses of amikacin with or without piperacillin in the serum bactericidal test. AB - To determine whether high doses of amikacin would prevent the development of resistance in clinical isolates, the serum bactericidal activity and killing rate of conventional and high doses of amikacin and piperacillin alone and in combination were measured in volunteer sera against a series of ten strains each of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Amikacin serum levels were 24.9 +/- 6.0 mg/l 1 h after infusion of the 7.5 mg/kg dose and 44.8 +/- 5.0 mg/l after the two-fold dose. Median serum bactericidal titers for low dose piperacillin + amikacin were 1:8-1:64 and for high-dose piperacillin + amikacin 1:16-1:128. Both were satisfactory, except against piperacillin resistant Pseudomonas aeruginosa (median bactericidal titers less than or equal to 1:2), and both combinations had equivalent killing rates. PMID- 3084249 TI - Autolysis of thermolysin. Isolation and characterization of a folded three fragment complex. AB - Incubation of the neutral metalloendopeptidase thermolysin at pH 7.2 in the presence of EDTA and/or low concentrations of calcium ions produces fast enzyme inactivation as a result of autolysis. The 'nicked' protein is a folded species composed of three tightly associated protein fragments. Dissociation of this complex can be achieved under denaturing conditions, such as gel filtration on a column equilibrated with 5 M guanidine hydrochloride or reverse-phase high performance liquid chromatography (HPLC) at acidic pH. The positions of the peptide bond cleavages were defined by isolation of the individual fragments by HPLC and their characterization by amino acid analysis after acid hydrolysis, end group determination and partial amino acid sequencing. The results of these analyses indicated that the nicked protein is composed of fragments 1-196, 197 204 and 205-316 and thus that the corresponding sites of limited proteolysis occur at the polypeptide chain loop involved in the binding of Ca(4) in native thermolysin [Matthews, B. W., Weaver, L. H. and Kester, W. R. (1974) J. Biol. Chem. 249, 8030-8044]. The overall conformational properties of nicked thermolysin are quite similar to those of the intact protein, as judged by spectroscopic measurements and by the fact that rabbit antibodies against native thermolysin recognize and precipitate the nicked protein in immunodiffusion assays. The nicked protein was much less stable to heat and unfolding agents than intact thermolysin. These results contribute to a better knowledge of the molecular mechanism of stabilization of native thermolysin by the four bound calcium ions and demonstrate that the function of Ca(4) is to stabilize the loop 190-205 on the surface of the molecule against autolysis. PMID- 3084250 TI - Purification and reconstitution properties of human placental aromatase. A cytochrome P-450-type monooxygenase. AB - The hemoprotein component of human placental aromatase (estrogen synthetase) has been purified to a high degree of homogeneity by a combination of affinity and adsorption chromatography on aminohexyl-Sepharose, concanavalin-A-Sepharose, and hydroxyapatite. The monomeric form of the enzyme has an Mr of 55000 +/- 1000 as estimated by sodium dodecyl sulfate gel electrophoresis. Its absolute spectrum shows a high-spin Soret band at 394 nm while its reduced, CO-difference spectrum has a maximum at 447 +/- 1 nm. Full reconstitution of aromatase activity was obtained when it was recombined with a homogeneous preparation of the higher-Mr form of either human placental, or bovine hepatic NADPH-cytochrome P-450 reductase. Critical factors for purification of the very unstable, membrane-bound hemoprotein with good retention of activity were, besides the chromatographic sequence, the use of the zwitterionic detergent 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate (Chaps) during the solubilization, and the stabilizing effect of the aromatase substrate, 4 androstene-3,17-dione, throughout the procedure. In the presence of NADPH, the reconstituted enzyme system smoothly aromatizes 19-oxoandrostenedione, 19 hydroxyandrostenedione and androstenedione in this order of reactivity. The same reconstituted system also aromatized testosterone, but it was inactive towards 19 norandrostenedione. Known cytochrome P-450 inhibitors decreased its activity. We conclude: (a) the terminal oxidase of human placental aromatase is indeed a cytochrome P-450-type monooxygenase; (b) the multistep aromatization reaction of C19 androstenes is catalyzed by a single enzyme; (c) aromatization of 19 norsteroids reported by other authors must be due to a different aromatase. Experimental data obtained with the reconstituted enzyme are fully compatible with the concept of a reaction mechanism for the aromatization sequence involving an all-trans, antiparallel elimination of the 19-methyl group, the 2 beta proton and the 1 alpha proton, rather than the 1 beta proton, as generally assumed. PMID- 3084251 TI - Complement deposition from human sera on silicon surfaces studied in situ by ellipsometry. The influence of surface wettability. AB - Organic material deposition from human sera on silicon dioxide surfaces was studied in situ by means of ellipsometry, an optical method for quantification of thin organic films. The deposition of organic material from sera was followed continuously for 2 h on hydrophobic and hydrophilic silicon surfaces. Both types of surfaces adsorbed organic material and the additional incubation with anti-C3 resulted in further deposition of organic material indicating the presence of C3 in the organic layers. Addition of EDTA in serum or heat inactivation resulted in a decrease of the amount of organic material deposited on the hydrophobic surface as well as in a lack of subsequent anti-C3 deposition on both hydrophilic and hydrophobic surfaces. Preadsorption with immunoglobulin G on the surfaces caused a pronounced increase of the deposition of material from serum as well as of subsequent anti-C3 deposition. Both effects were absent if EDTA was present in the serum. Our results indicate that complement activation and deposition occur by incubation of human sera on hydrophobic and hydrophilic silicon dioxide surfaces, which are two surfaces with very simple and well-defined chemical composition. The degree of the reversibility of the deposition of immunoglobulin G was furthermore larger on hydrophilic silicon. PMID- 3084253 TI - Activation of bovine muscle carbonic anhydrase by modification of thiol groups. AB - Two of the five cysteine residues in bovine muscle carbonic anhydrase (isoenzyme III) react rapidly and stoichiometrically with Ellman's reagent without effect on the CO2 hydration activity. These residues, which can be alkylated with iodoacetamide, have been identified as Cys-183 and Cys-188. Treatment of the enzyme with a large excess of Ellman's reagent results in additional derivatization of thiol groups and a 180% increase of the CO2 hydration activity. The cysteine residues associated with this activation are Cys-66 as well as Cys 203 and/or Cys-206. Activation has also been achieved with 2,2'-dithiodipyridine (120%) and with methyl methanethiosulfonate (approx. 400%), whereas no activation could be obtained with iodoacetamide, iodoacetate or N-ethylmaleimide. PMID- 3084252 TI - Galactose- and maltose-stimulated lipoamide dehydrogenase activities related to the binding-protein-dependent transport of galactose and maltose in toluenized cells of Escherichia coli. AB - The binding protein-dependent transport of galactose and maltose occurs at a reduced but significant rate in Escherichia coli cells which have undergone a mild toluenization. Dihydrolipoate and 3-acetyl-NAD produce a severalfold stimulation of these transports in the toluenized cells. In parallel to the stimulation of galactose and maltose transport by dihydrolipoate and 3-acetyl NAD, there is a stimulation by galactose and maltose of lipoamide dehydrogenase activities which seem to be related to the binding-protein-dependent transport of these sugars. The lipoamide dehydrogenase component of the pyruvate and 2 oxoglutarate dehydrogenase complexes (the lpd gene product) is not involved in this stimulation. These results are discussed in relation to our recent studies showing a possible involvement of lipoic acid and of the 2-oxoacid dehydrogenases in the binding-protein-dependent transports. PMID- 3084255 TI - Rapid-scan stopped-flow studies of the pH dependence of the reaction between mercuric reductase and NADPH. AB - The reaction of NADPH with the flavoenzyme mercuric reductase has been studied by rapid-scan stopped-flow spectrophotometry at 5 degrees C in the pH range 5.1-9.5. An intermediate formed within the dead time of the apparatus, and proposed to be an NADPH complex of oxidized enzyme, has an almost pH-independent spectrum. At pH 5.1 the formation of this species is followed by a rapid bleaching (k = 145 s-1) of the main flavin absorption band at 455 nm concomitantly with an absorbance increase around 395 nm. This process, which has a kinetic hydrogen isotope effect of 2.4, becomes less prominent at higher pH values and is not detectable above pH 7. It is suggested that this process includes the formation of a covalent thiol flavin C-4a derivative stabilized by protonation of the active site. In the presence of an excess of NADPH, the final product of the reaction is probably an NADPH complex of two-electron-reduced enzyme, but below pH 6 the final spectrum becomes less intense suggesting a partial formation of four-electron-reduced enzyme. The spectral changes observed above pH 7 are nearly independent of pH. The first measurable step (k = 48 s-1 at pH 9.5) is thought to include the formation of an NADP+ complex of two-electron-reduced enzyme, while the final step (k = 6.3 s-1 at pH 9.5) results in the above-mentioned NADPH complex with two-electron-reduced enzyme. A minimal kinetic scheme rationalizing the observed pH dependence of the reaction and the observed isotope effects is presented. PMID- 3084254 TI - Purification and structural characterization of intact and fragmented nidogen obtained from a tumor basement membrane. AB - Extraction of a basement-membrane-producing mouse tumor with 6 M guanidine/HCl in the presence of protease inhibitors allowed the purification of the genuine form of the matrix protein nidogen (Mr = 150,000) and, in addition, two defined fragments (Mr = 130,000 and 100,000). Smaller fragments (Mr = 80,000 and 40,000) were obtained under conditions with less stringent control of endogenous proteolysis. Intact nidogen and the larger fragments were similar in amino acid and carbohydrate (about 5%) composition, the presence of a single polypeptide chain, conformational features as revealed by CD spectroscopy and all shared major epitopes located on the Mr = 80,000 fragment. Additional epitopes were found on intact nidogen and the Mr = 130,000 fragment. Nidogen and the various fragments possess different N-terminal amino acid sequences indicating a stepwise degradation from the N-terminal end of the molecule. Electron microscopical and hydrodynamic studies of the Mr = 80,000 fragment demonstrated a structure consisting of a globular head connected to a thin tail. Intact nidogen appears to contain a somewhat larger globule but the same tail, which is terminated at its opposite end by a second, smaller globular structure. The data suggest a multidomain structure for nidogen containing sites highly susceptible to proteolytic cleavage. PMID- 3084256 TI - The increase by spermidine of fidelity of protamine synthesis in a wheat-germ cell-free system. AB - The influence of spermidine on the fidelity of natural mRNA-directed protein synthesis has been investigated. With protamine mRNA as a template for protamine synthesis, misincorporation of lysine, histidine, threonine and cysteine for arginine was measured in the presence and absence of spermidine. It was found that misincorporation of these four amino acids in the presence of spermidine was less than or nearly equal to that occurring in the absence of spermidine; however, incorporation of arginine was stimulated greatly by spermidine. These results clearly show that spermidine induced an increase of fidelity in protamine synthesis. The increase of fidelity in the presence of spermidine occurred mainly at the level of binding of aminoacyl-tRNA to ribosomes. The frequency of misreading the 5' base of the codon (misincorporation of cysteine) was greater than that of the middle base of the codon (misincorporation of histidine), but spermidine reduction of misreading was more marked at the middle base of the codon. Misincorporation of lysine (misreading of G to A residue at the middle base of the codon) was greater than that of threonine (misreading of G to C residue), but spermidine reduction of misreading was more marked in the misincorporation of threonine. It was deduced from these results that spermidine inhibited low-frequency misreading more effectively than high-frequency misreading. PMID- 3084257 TI - Structural studies of the carbohydrate chains of human gamma-interferon. AB - Human gamma-interferon (IFN-gamma) was prepared biotechnologically using Chinese hamster ovary cells. These cells were shown to be able to produce glycosylated IFN-gamma. Sugar analysis revealed the presence of Man, Gal, GlcNAc, NeuAc and Fuc residues in a molar ratio of 3.8:2.0:3.5:0.6:0.4 suggesting the occurrence of N-glycosidically linked N-acetyllactosamine type of carbohydrate chains. For structure determination of these chains, the glycoprotein was subjected to the hydrazinolysis procedure, yielding oligosaccharide-alditols. The latter compounds were analysed by 500-MHz 1H-NMR spectroscopy. The carbohydrate material was found to consist of biantennary structures, exhibiting microheterogeneity as to the terminal sialic acids and the core Fuc residue: (Formula: see text). As similar carbohydrates are present on several human secreted proteins, this glycosyl group is not expected to be immunogenic in man. It remains to be established to what extent the carbohydrate chains of this biotechnologically produced IFN-gamma are identical to those of naturally occurring human IFN-gamma. PMID- 3084258 TI - Preoperative treatment of squamous cell carcinoma of the lung with mitomycin-C in the bronchial artery. AB - Five patients with clinically inoperable bronchial squamous cell carcinoma were treated with infusions of 10 mg Mitomycin-C in the bronchial artery feeding the tumour, in an attempt to make inoperable bronchogenic carcinoma resectable. One patient had only one treatment while the other four had the infusion repeated three times with an interval of two weeks between treatments. In all cases there was a marked regression of the tumour. Four patients had the tumour resected 1-2 weeks following the last treatment and two of these are still alive 2 1/2 and 4 years later. The other two patients died 14 and 22 months following the initiation of the treatment. The fifth patient developed serious adverse effects to the drug that only slowly subsided. He died 5 1/2 months following the initiation of the treatment and his tumour was not resected. This limited study demonstrates the possibility of making certain inoperable patients with bronchogenic carcinoma operable, but it also stresses the problems of a correct preoperative staging. PMID- 3084259 TI - A centriole-free Drosophila cell line. A high voltage EM study. AB - The problem of the absence of centrioles in cells of the 1182-4 line of Drosophila melanogaster has been reexamined with high voltage electron microscopy. A hypotonic treatment of the cells before fixation allowed a clear recognition of centrioles in 1 micron thick sections. Three different approaches were used to determine the presence of absence of centrioles in a Kc control cell line and in the 1182-4D cell line. 1) 1500 random 0.5 micron thick sections representing the equivalent of 60 whole cells of the 1182-4D line show no centrioles. In contrast, nearly all centrioles of the Kc cells were detected by this examination. 2) In a blind test 10 grids with either Kc or 1182-4D cells were correctly identified by the operator. In Kc cells, 4 to 6 diplosomes were observed by grid square on about 300 cell profiles, while no centrioles were seen in the sections of 1182-4D cells. 3) Complete serial sections 1 micron thick of whole 1182-4D cells were screened for presence or absence of centriole. No centriole was seen in any section. We conclude that these Drosophila 1182-4D cells, which have been maintained in culture for several years, are free of centrioles. PMID- 3084260 TI - Cationized ferritin as a platelet-stimulating surface probe. Binding to platelets and effects on platelet function. AB - Polycationic derivatives of ferritin containing primary amino groups (CFah) or tertiary amino groups (CFdmp) were potent platelet agonists inducing shape change, aggregation and secretion, but also agglutination in the presence of EDTA. Pretreatment of platelets with neuraminidase, PGE1, indomethacin, or creatine kinase/creatine phosphate inhibited CF-induced activation. In contrast, neuraminidase and PGE1 increased the agglutination by CF, indicating an inverse relationship between activation and CF-induced agglutination. At pH 7.4, the cationic charges of CFdmp exceeded those of CFah by a factor of 1.5 and the platelets bound approximately 1.5 times more CFah than CFdmp, suggesting the same number of anionic surface sites for both CF preparations. The capacity of the platelets to bind CF was diminished by 55% at 0 degree C or by 62% after aldehyde fixation and by 13% with PGE1. This suggests that the binding capacity depends on the mobility of the binding sites in the plane of the membrane but is only slightly increased by platelet activation. Binding to fixed or cold platelets approached equilibrium within a few seconds whereas saturation required several minutes at 37 degrees C. Neuraminidase preferentially reduced the slow binding and much less the rapid binding. Since activation by CF developed during seconds, suppressible by a brief treatment with neuraminidase 25 mU/ml, a small portion of neuraminidase-sensitive sites appears to be necessary for CF-induced platelet activation. Full activation and agglutination occurred at CF concentrations far below saturating concentrations. The results show that neither CF-induced activation nor agglutination depend on a simple neutralization of the negative surface charge. PMID- 3084261 TI - Immunoelectron microscopical localization of lysosomal beta-galactosidase and its precursor forms in normal and mutant human fibroblasts. AB - Immunoelectron microscopy was performed to study the biosynthesis of lysosomal beta-galactosidase (beta-gal) in normal and mutant human fibroblasts. Using polyclonal and monoclonal antibodies we show in normal cells precursor forms of beta-gal in the rough endoplasmic reticulum (RER) and in the Golgi apparatus throughout the stack of cisternae. In the lysosomes virtually all beta-gal exists as a high molecular weight multimer of mature enzyme. In the autosomal recessive disease GM1-gangliosidosis caused by a beta-gal deficiency and in galactosialidosis, associated with a combined deficiency of lysosomal neuraminidase and beta-gal, precursor forms of the latter enzyme are found in RER, Golgi and some labeling is present at the cell surface. The lysosomes remain unlabeled, indicative for the absence of enzyme molecules in this organelle. In galactosialidosis fibroblasts also no mature beta-gal is found in the lysosomes but in these cells the presence of the monomeric form can be increased by leupeptin (inhibition of proteolysis) whereas addition of a partly purified 32 kDa "protective protein" results in the restoration of high molecular weight beta gal multimers in the lysosomes. PMID- 3084262 TI - Binding of estrogen receptor from N-nitrosomethylurea-induced rat mammary tumors to nuclei. AB - The binding of the cytoplasmic estrogen receptor (ERc) from N-nitrosomethylurea (NMU)-induced rat mammary tumors to the nucleus using a cell-free system is described. All tumors studied were estrogen-receptor-positive and most of them were hormone-dependent. Sixty-two percent of all tumors investigated (n = 134) decreased in size more than 30% 4-5 days after ovariectomy. Brief heating of the cytosol loaded with tritiated estradiol induced activation of the ERc measured by an increase of nuclear binding activity. Temperature-dependent activation was evident in every case. The optimal time and temperature of activation were 15-60 min at 30 degrees C. After denaturation of the ERc by heating for 20 min at 56 degrees C only small parts of free estradiol could be bound to nuclei. Mg2+ ions and EDTA inhibited the nuclear binding of the receptor. The nuclear binding assay was performed for 1 hr at 0-4 degrees C. After this time the activated ERc was bound nearly maximally to nuclei. Under optimized conditions 50-60% of the ERc could be bound to nuclei maximally. Using the same medium for the preparation of crude and purified nuclei the binding of the receptor to both kinds of nuclei was similar. Na2MoO4 prevented the activation of the ERc from NMU-tumors completely but did not influence the binding of the previously activated receptor to nuclei. PMID- 3084263 TI - Evaluation of galactosyltransferase isoenzyme II in a human colon carcinoma derived cell line, HCT-8. AB - Polyacrylamide gel electrophoresis of galactosyltransferase (GT) extracted from a human colon adenocarcinoma cell line, HCT-8, demonstrated the presence of two peaks of activity: a slow-moving peak, referred to as GT-II, and a more anodally migrating peak, designated as GT-I, which was also found for normal human serum. However, if GT solubilized from HCT-8 cells was separated by isoelectric focusing, no unique isoenzymes could be detected. Total GT activity from HCT-8 cells was purified by alpha-lactalbumin-Sepharose affinity chromatography followed by ion exchange chromatography on either DEAE-cellulose or FPLC using a Mono Q anion exchange resin. Three major peaks of activity were resolved from anion exchange chromatography. Electrophoresis of each peak revealed a GT pattern identical with that originally observed for the crude (detergent) solubilized homogenate. No enrichment of either GT-I or GT-II was observed in the three enzyme fractions. The data suggest that GT-II may be an artifactual activity of cancer cells composed of GT-I associated with some contaminating protein. PMID- 3084264 TI - False-positive ketonuria during ifosfamide and mesna therapy. PMID- 3084265 TI - Creatine kinase and creatine kinase B-subunit in stable and unstable angina pectoris. AB - Repetitive ischaemic episodes may have a cumulative effect leading to irreversible myocardial cell damage with enzyme release. Using plasma creatine kinase (CK) and creatine kinase B-subunit (CK-B) concentrations this theory has been tested in forty-eight patients admitted with acute chest pain, but without ECG signs of acute myocardial infarction (AMI). The patients were classified into four groups: Fourteen patients with non-ischaemic heart disease (non-IHD), seventeen with stable angina pectoris (SAP), ten with unstable angina pectoris (UAP), and seven patients who developed AMI during the study period. The enzyme variation in non-IHD delineates the background noise, and the increased variability in AMI indicates the full scale of the enzyme signals in cases of irreversible cell damage. Patients with SAP have the same enzyme signal as the background noise in respect of both CK and CK-B. However, in UAP the signal of CK B equals the background noise, whereas the CK signal is separated from the latter. The reason may be that the signal to noise ratio of CK-B is poor and the analytical sensitivity low. Therefore, the behaviour of CK-B in this study does not support the above theory although our findings for CK indicate that the consequence of repeated ischaemic attacks is slight enzyme release. PMID- 3084266 TI - Influence of peroral antibiotics upon the biotransformatory activity of the intestinal microflora in healthy subjects. AB - The effects of ampicillin, clindamycin or metronidazole, given perorally for 6 days to eighteen healthy volunteers, upon the following intestinal microflora associated characteristics (MACs) were evaluated: breakdown of mucin, formation of coprostanol, hydrolysis of bilirubin conjugates, formation of urobilinogen, and of some short chain fatty acids (SCFAs), presence of beta-aspartylglycine and inactivation of trypsin. Clindamycin markedly influenced the expression of all characteristics, but trypsin and beta-aspartylglycine, resulting in a pattern very much alike what has been found in germ-free animals. Ampicillin caused a significant reduction in total amount of SCFAs (P less than 0.05) and urobilinogen (P less than 0.05) present in the faecal samples. Metronidazole caused a significant reduction in the formation of coprostanol and the deconjugation of bilirubin (P less than 0.05). We conclude that orally given antibiotics may cause major alterations in several parameters reflecting the normal biotransformatory activity of the intestinal microflora, probably caused by severe disturbances in the intestinal ecosystem. PMID- 3084267 TI - Comparison of plasma 3,4-dihydroxyphenylethylene glycol (DHPG) and norepinephrine levels as indices of sympathetic activity in man. AB - Plasma levels of norepinephrine (NE) and the NE metabolite 3,4 dihydroxyphenylethylene glycol (DHPG) were measured simultaneously following sympathetic activation induced by standing, cold pressor testing and bicycle exercise at progressively increasing workloads in normal volunteers. Free DHPG and NE levels both increased with sympathetic activation, but free NE levels were a more sensitive index of change. In addition, plasma free NE levels more closely reflected the fall in heart rate following exercise than free DHPG. In contrast to free levels, conjugated DHPG and NE levels did not change significantly after exercise. Supine resting free DHPG/NE ratios were always greater than 2.0, but fell progressively with increasing sympathetic activation because of a proportionately greater rise in NE than DHPG. The simultaneous measurement of plasma free DHPG and NE does not offer advantages over free NE levels as an index of sympathetic activity in man, but may be of use in the diagnosis of pheochromocytoma and in studies of NE metabolism. PMID- 3084268 TI - Warfarin binding to plasma albumin, measured in patients and related to fatty acid concentrations. AB - A method for determination of reserve albumin equivalent for binding of warfarin as previously described [1] has been used for assessing the influence of non esterified fatty acid concentration (NEFA) on binding of warfarin to human serum albumin (HSA). Reserve albumin concentration can be used for calculation of the expected fraction of bound warfarin in serum. It is shown in vitro that binding of warfarin increases with added oleate up to 4 mol of oleate per mol of albumin and then decreases. Twenty-four patients on permanent warfarin treatment showed no correlation of serum albumin and reserve albumin concentrations (r = 0.10, P greater than 0.50) indicating that warfarin binding is governed by other factors. However, in the same patients there was a significant correlation between reserve albumin concentration and NEFA/HSA (r = 0.54, P less than 0.01). In one human volunteer changes of NEFA were provoked by strenuous work and it was found that reserve albumin concentration increased with NEFA concentration as expected from the in vitro findings (r = 0.90, P less than 0.001). Five uraemic patients on permanent warfarin treatment showed increasing reserve albumin concentration with increasing NEFA concentration induced by heparin. These findings indicate that, both in vitro and in vivo, the reserve albumin concentration for binding of warfarin and hence the free warfarin concentration is markedly influenced by NEFA concentration. This may add to the understanding of warfarin dose requirement during anticoagulant therapy. PMID- 3084269 TI - Serum isoamylase activities during infusions of glucose and amino acids. AB - This investigation was undertaken to examine the influence of intravenously administered glucose and amino acids on serum isoamylase activities. Significantly decreased serum pancreatic isoamylase was observed during administration of 20% glucose and 8% amino acid solutions intravenously for 2 h as compared with physiological saline solution (P less than 0.005). A significant negative correlation was found between mean values of pancreatic isoamylase (P isoamylase) in serum and glucose in plasma (r = 0.91, P less than 0.01). We propose that glucose may block the flux of pancreatic amylase across the basolateral membrane of the acinar cell into the blood stream. The mechanisms by which amino acids may decrease P-isoamylase activity in serum are not quite clear. Amino acid stimulated release of pancreatic glucagon which has an inhibitory effect on amylase secretion is highly probable. PMID- 3084270 TI - Survival of gentamicin-loaded carrier erythrocytes in healthy human volunteers. AB - Resealed erythrocytes are potential slow release carriers for drugs and enzymes. We have investigated carrier erythrocyte survival in human volunteers using gentamicin (G) as encapsulated cell marker; G was readily incorporated into red cells by hypo-osmotic dialysis (87% efficiency of incorporation) and did not exit from carrier cells in vitro. Six healthy young volunteers were injected with 59 +/- 7 ml carrier erythrocytes containing 56 +/- 13 mg G. G levels were measured in plasma and haemolysed whole blood by RIA. After an initial phase of cell loss (up to 4.5 h post-injection) the carrier erythrocytes survived in circulation with a half-life of 22 days, as was indicated by intracellular G concentration. G levels were detectable in plasma during the first 90 min after injection. This indicates haemolysis of some carrier cells. In conclusion, carrier erythrocytes appear to circulate longer than any other drug carrier under investigation and may well serve as innocuous slow release system. PMID- 3084271 TI - Ex vivo perfusion of plasma over protein A columns in human mammary adenocarcinoma. Evidence for a protein A leaking by radioimmunoassay. AB - A solid phase radioimmunoassay (RIA) has been developed for detection of protein A in human serum or plasma using plates coated with specific goat anti-protein A IgG and affinity-purified anti-protein A F (ab')2 fragments labelled with 125Iodine as a tracer. This RIA detected 25 ng of protein A per ml of serum or plasma. The 'intra-plate' coefficient of variation (CV) was 4.26%, whereas the 'inter-plate' CV was 5.86%, even in the presence of aggregated IgG. The presence of protein A was searched for by this RIA in samples collected during ex vivo perfusion of the plasma of patients suffering from a metastatic mammary adenocarcinoma either over columns of 'native' protein A (seven patients; group A) or over columns of protein A in which the Fc-binding capacity was destroyed (five patients; group B). A protein A leaking occurred with the same incidence (about 20% of the sessions) in both groups. However, major acute side effects (hypotension, chills, mild fever, etc.) and necrolytic responses were seen only in some patients from group A. In these cases, the incidence of side effects, but not of tumoricidal responses, increased with the protein A serum concentrations reached 1 h after the end of the sessions (25-150 ng ml-1). The data suggest that the therapeutic efficacy of ex vivo protein A immunoadsorption in breast cancer is related to the Fc-binding capacity of the columns rather than to a leakage of 'native' protein A into the blood stream. PMID- 3084272 TI - Haemodynamic and hormonal responses to exercise: studies in patients with diabetes mellitus and adrenomedullary deficiency. AB - The haemodynamic and hormonal responses of patients with autonomic neuropathy and others with adrenomedullary deficiency were compared with mild hypertensives (range of blood pressure 90-100 mmHg diastolic and 140-160 mmHg systolic) and uncomplicated diabetics during standard exercise and postural manoeuvres using continuous arterial blood pressure monitoring. There was no difference in these parameters between the groups when at rest or on standing. During exercise there was no significant difference in blood pressure and heart rate between the groups and all showed significant increases in plasma noradrenaline (mean rise for all groups 2730-22 105 pm 1(-1), P less than 0.03) and (in all but the adrenalectomized subjects) adrenaline (mean rise for remaining three groups 946 3384 pm 1(-1), P less than 0.03; adrenalectomized group showed no rise). The group with autonomic neuropathy showed a significant rise in plasma cortisol from basal 450 +/- 40 to 845 +/- 72 nm 1(-1), P less than 0.005 after exercise, but the other groups showed no significant change. The maximum level attained for plasma cortisol in the adrenalectomized subjects after exercise was significantly less (260 +/- 41 nm 1(-1) than in the diabetic groups (696 +/- 68 nm 1(-1) (non neuropaths), 845 +/- 72 nm 1(-1) (neuropaths), P less than 0.01). We have demonstrated normal blood pressure and pulse responses to posture and sustained exercise in diabetics with autonomic neutropathy. The findings of similarly normal responses in patients with adrenomedullary deficiency suggest that circulating adrenaline is not obligatory to a normal haemodynamic response to exercise. PMID- 3084273 TI - Ex vivo perfusion of plasma over protein A columns in human mammary adenocarcinoma. Role of the Fc-binding capacity of protein A in the side effects and the tumoricidal response. AB - Plasma of twelve patients presenting with a metastic mammary adenocarcinoma was perfused ex vivo over columns of protein A covalently linked to crystalline silica. The plasma of seven patients (group A) was perfused over columns of protein A exhibiting a normal Fc-binding capacity and the plasma of five (group B) over columns of protein A in which the Fc-binding capacity was destroyed. In group A, all patients experienced acute, easily manageable, side effects (hypotension, chills, mild fever, leucocytosis and pain in tumour sites) during or immediately after the immunoadsorption procedures, and three exhibited an objective partial regression after two to five sessions. In contrast, none of the patients from group B developed any acute side effects and all showed evident progression of their disease during the treatment. Tumour cells in all stages of destruction, sometimes surrounded by extensive fibrosis, were seen in biopsies of patients A. However, focal areas of active tumour proliferation were always present in these patients. These data confirm that ex vivo perfusion over protein A columns of plasma from patients with cancer can induce a tumoricidal response in some instances and show that the Fc-binding capacity of protein A is most probably responsible for the necrolytic response and the side effects. PMID- 3084274 TI - Angiotensin II, aldosterone and arginine vasopressin in plasma in congestive heart failure. AB - Angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) in plasma were determined during basal conditions in seventeen patients with congestive heart failure and in seventeen control subjects. The same parameters were measured before and 1, 2 and 3 h after an oral water load of 20 ml (kg body weight)-1 together with urine volume (V) and free water clearance (CH2O) in seven patients with congestive heart failure and in seven control subjects. AII, Aldo and AVP were significantly higher in heart failure than in control subjects (AII:81 and 12 pmol l(-1) (medians), P less than 0.01; Aldo: 411 and 103 pmol l( 1), P less than 0.01; AVP: 5.3 and 2.0 pmol l)-1), P less than 0.01). AVP was positively correlated to Aldo in both heart failure (p = 0.593, n = 17, P less than 0.02) and control subjects (p = 0.511, n = 17, P less than 0.05), but in neither of the groups to AII. V and CH2O were significantly lower in heart failure when compared to control subjects (maximum increase in CH2O 3.55 and 5.86 ml min-1, P less than 0.02), but did not correlate directly with either A II, Aldo or AVP. Creatinine clearance was reduced in heart failure. It is concluded that the activity of both the renin-angiotensin-aldosterone system and the osmoregulatory system is enhanced in congestive heart failure, presumably as a compensatory phenomenon in order to maintain arterial blood pressure. It is suggested that the decrease in free water clearance may be attributed to both an elevated level of vasopressin and a reduced glomerular filtration rate. PMID- 3084275 TI - Change in very low-, low-, and high-density lipoproteins during lipid lowering (bezafibrate) therapy: studies in type IIA and type IIb hyperlipoproteinaemia. AB - The effects of lipid lowering therapy (bezafibrate) on plasma lipoproteins was investigated in twelve patients with familial hypercholesterolaemia (type IIA) and eight with familial combined hyperlipidaemia (type IIB). Bezafibrate caused a decrease of plasma cholesterol, plasma triglycerides, plasma apolipoprotein B, VLDL cholesterol and LDL cholesterol and an increase of HDL cholesterol. Post heparin plasma lipoprotein and hepatic lipase activities increased in both groups (significant only in type IIB). Lipoprotein composition showed the following changes: Increased protein and phospholipids and decreased triglycerides and cholesteryl esters in VLDL. Decreased protein and triglycerides and increased free and esterified cholesterol in LDL. Decreased triglycerides and increased phospholipids in HDL. Cholesteryl ester to protein ratios decreased in VLDL and increased in LDL. The hydrated density of LDL (both groups) and of HDL3 (type IIB) decreased following bezafibrate therapy. These changes were in general similar to those observed in hypertriglyceridaemic patients and could be ascribed, at least in part, to the increase of plasma lipase activities and the decrease of lipid transfer reactions. Comparing the present data with that previously reported, it was found that bezafibrate caused decreased LDL cholesterol in types IIA and IIB but increased levels in type IV. This change was correlated with the initial plasma triglycerides (r = 0.74, P less than 0.0001) and initial plasma LDL cholesterol (r = 0.66, P less than 0.001). It is concluded that varied response of LDL to therapy reflects a complex interaction of metabolic events, including changing rates of VLDL conversion to LDL, lipoprotein compositional changes and effects of therapy on LDL degradation rates. PMID- 3084276 TI - Nephrotoxicity of cyclosporin A. A lithium clearance and micropuncture study in rats. AB - Renal function was studied in rats treated with cyclosporin A (CyA). Peroral CyA 25 mg kg-1 day-1 depressed glomerular filtration rate (GFR) from 1284 +/- 429 to 500 +/- 228 microliters min-1 g-1 kidney weight (KW) (P less than 0.01). Absolute rate of proximal tubular reabsorption (APR) decreased from 1075 +/- 437 to 468 +/ 203 microliters min g KW-1 (P less than 0.01). Proximal tubular fractional reabsorption (PFR) was 67.7 and 68.5% measured with the TT/OT and fractional lithium-clearance methods, respectively. Amiloride had no effect on lithium clearance in CyA treated rats. Acute isotonic volume expansion increased GFR and APR towards normal, while PFR remained increased. Increased sodium clearance did not normalize renal function. CyA intravenously (12.5 mg kg-1) depressed GFR and APR acutely, while PFR increased. Proximal intratubular pressures were low normal (mean 11.6 mmHg). Proximal transit times were prolonged (mean 25.2 s, P less than 0.01). Renal morphology was normal. The data are evidence against a primary tubular damage of CyA, and makes it less likely that the major lesion is located to the glomerular membrane. The results suggest that CyA nephrotoxicity mainly is due to a haemodynamic effect. PMID- 3084277 TI - Relationship of angiotensin II, aldosterone, arginine vasopressin, adrenaline and noradrenaline in plasma, blood and extracellular volumes to blood pressure in chronic glomerulonephritis. AB - Blood volume, extracellular volume, blood pressure and the plasma levels of angiotensin II, aldosterone, adrenaline, noradrenaline and arginine vasopressin were determined in sixteen normotensive (group 1) and thirteen hypertensive patients (group 2) with chronic glomerulonephritis and in eleven normotensive control subjects (group 3). Blood volume and extracellular volume did not differ between the groups and no significant differences were found in any of the hormones measured when comparing group 1 or group 2 with group 3. In the hypertensives but not in the normotensives or control subjects, a highly significant positive correlation was found between diastolic blood pressure and blood volume (rho = 0.75, P less than 0.01) and between diastolic blood pressure and extracellular volume (rho = 0.74, P less than 0.01). Blood volume and extracellular volume correlated (P less than 0.05) in each of the groups. In conclusion, although no expansion of either blood or extracellular volume was found in chronic glomerulonephritis, a positive volume-pressure relationship could be demonstrated in hypertensive patients suggesting a role of volume factors in the pathogenesis in early stage chronic glomerulonephritis. The study does not give support to a major role of either angiotensin II, arginine vasopressin or catecholamines in the maintenance of nonmalignant hypertension in early stage chronic glomerulonephritis. PMID- 3084278 TI - Immunoglobulin deposits in labial mucosal epithelium of patients suspected of Sjogren's syndrome. AB - Lower lip biopsies from twenty-three consecutive patients under evaluation for Sjogren's syndrome, and from six normal controls, were investigated for deposits of immunoglobulins, fibrinogen and C3, using a direct immunofluorescence technique. Deposits of both IgG and IgA were demonstrated in the mucosal epithelium in three of six patients with primary Sjogren's syndrome. Similar IgG deposits were found in two of three patients with xerostomia and in one of three patients with Sjogren's syndrome secondary to rheumatoid arthritis. Immunoglobulins were located in close relation to cell surfaces in the basal and suprabasal layers of the epithelium. Double labelling experiments indicated a partial topographic concordance between the immunoglobulin deposits and OKT6 positive Langerhans cells in the epithelium. No deposits of immunoglobulins, fibrinogen or C3 were found in the remaining eleven patients and six normal controls. We conclude that deposits of IgG and IgA in the labial mucosal epithelium seem to be a characteristic finding in patients with primary Sjogren's syndrome as well as in patients with xerostomia. The diagnostic value of this new observation needs to be clarified in future studies. PMID- 3084279 TI - The commitment of secretory cells to the selective expression of immunoglobulin CH genes is determined by the available concentrations of the triggering ligand. AB - The property of lipopolysaccharide to induce B cells to both proliferate and differentiate to IgM, IgG3 and IgG2b expression can be ascribed either to a precommitted sequence of molecular events in the activated B cells or, alternatively, to separate activities which independently modulate the two events. To discriminate between these two possibilities we have investigated the relationship between the doses of the polyclonal stimulus and the commitment of the activated cells to proliferate and to produce various isotypes. Low doses of ligand supported proliferation as well as IgM but not IgG2b secretion. On the contrary, high doses of the same ligand were less efficient in supporting proliferation but strongly induced heavy chain class switch. The effect of lipopolysaccharide concentrations on CH genes expression decayed with the distance from mu to the respective C gamma gene. Although we could define different B cell subsets on the basis of their proliferative response to various doses of the ligand, all these B subpopulations were found to be multipotential in terms of their switching capacity. Taken together our data show that in lipopolysaccharide cultures B cell proliferation and heavy chain switch are two events completely dissociable on the basis of their inducing requirements. PMID- 3084280 TI - Functional and mechanistic studies on the toxicity of deoxyguanosine for the in vitro proliferation and differentiation of human peripheral blood B lymphocytes. AB - Deoxyguanosine (dGuo) has been implicated as the toxic metabolite causing a severe impairment of cellular immunity in children with a genetic deficiency of purine nucleoside phosphorylase (PNP). In peripheral blood T cells of normal donors both the pathway which leads to phosphorylation of dGuo (ultimately resulting in deoxyguanosine triphosphate, dGTP) and the salvage pathway which starts with degradation of dGuo by PNP (resulting in the formation of guanosine triphosphate, GTP) contribute to the inhibition of proliferation. In normal peripheral blood B cells, addition of dGuo leads to an inhibition of proliferation and differentiation. The concentrations of dGuo needed to cause a 50% inhibition are equivalent for peripheral blood T cells and B cells. Inhibition of B cell differentiation can be observed at the level of intracytoplasmic as well as secreted Ig and concerns all Ig isotypes. The early phase of B cell activation which takes place during a 24-h preculture with formalinized Cowan I Staphylococci is not affected by dGuo; it is not until proliferation and differentiation of B cells, brought about by culturing in the presence of crude concanavalin A supernatant, occurs that inhibitory effects of dGuo become evident. Addition of dGuo to B cell cultures results in an intracellular accumulation of GTP and dGTP. Addition of 8-aminoguanosine, a PNP inhibitor, next to dGuo, completely prevents the dGuo-mediated inhibition. Under these circumstances the dGuo-mediated increase in intracellular GTP is abrogated while dGTP accumulation still occurs. This indicates that the inhibitory effect of dGuo on the proliferation and differentiation of peripheral blood B lymphocytes of normal donors is independent of dGTP accumulation. PMID- 3084281 TI - Induction or prevention of immunopathological disease by cloned cytotoxic T cell lines specific for lymphocytic choriomeningitis virus. AB - Cloned lymphocytic choriomeningitis virus (LCMV)-specific cytotoxic T lymphocyte (CTL) lines were prepared from spleens of 129/J (H-2b) mice immunized 7-9 months earlier with LCMV (UBC strain), or of C57BL/10J (H-2b) mice immunized 4 to 5 weeks earlier with LCMV (Armstrong strain). One uncloned and 3 cloned cytotoxic T cell lines were assessed for their respective abilities to produce, or protect against, fatal disease upon transfer to appropriate recipients or to induce specific footpad-swelling reaction. The effects of all lines were essentially identical. In recipient mice acutely infected with LCMV and immunosuppressed either by irradiation (750-990 rds) or treatment with cyclophosphamide, cloned T cells administered intracerebrally (i.c.) caused a convulsive disease and death within 1-4 days. No disease was produced when the same CTL were transferred to uninfected recipients or when they had been frozen and thawed prior to transfer to infected recipients. When admixed with 500 plaque-forming units of LCMV and transferred i.c. to immunocompetent H-2b mice, the T cell clones prevented overt disease. Allogeneic (H-2k) recipients of this same admixture all developed typical LCM disease as did H-2b recipients of the admixture after T cells had been frozen and thawed. Inoculation of cloned CTL into preinfected footpads induced a specific footpad-swelling reaction, which reached maximum levels after about 36 h. Irradiated and infected recipients of cloned LCMV-specific T cells showed the footpad-swelling reaction only when they had been reconstituted with bone marrow cells. In contrast, cloned T cells induced LCM disease in i.c. infected and irradiated mice independent of bone marrow reconstitution. These findings indicate that both fatal LCMV-induced neurologic disease and protection against it are mediated directly by virus-specific CTL. PMID- 3084282 TI - Modification of lymphocyte migration by sulfated polysaccharides. AB - The role of sulfated polysaccharides in lymphocyte migration has been analyzed in vivo using lymphocytes labeled with an intracellular DNA-binding fluorochrome Hoechst 33342. The influence of a panel of sulfated polysaccharides on entry (by injecting the sulfated polysaccharide prior to the labeled cells) and displacement from lymphoid organs (by injecting the sulfated polysaccharide after the labeled cells have localized) indicated that different sulfated polysaccharides have selective effects on entry and displacement, and furthermore positioning of subpopulations within organs. Additional experiments suggested that receptors for sulfated polysaccharides on high endothelial venules may interact with complementary structures on lymphocytes. The data supporting this conclusion were: (a) the normal localization behavior of lymphocytes preincubated with sulfated polysaccharides; (b) an inverse relationship between the expression of lymphocyte surface receptors for sulfated polysaccharides and the ability of the lymphocytes to enter lymphoid organs and (c) the selective binding of sulfated polysaccharide-coupled fluoresceinated beads to high endothelial venules. In this case only the beads coupled with the sulfated polysaccharides that inhibited entry bound to the high endothelial venules. These findings are discussed in terms of a fundamental cellular recognition system utilizing sulfated polysaccharides. PMID- 3084283 TI - Peritoneal Ly-1 B cells: genetic control, autoantibody production, increased lambda light chain expression. AB - Previous studies demonstrate that Ly-1 B cells and their progenitors are clearly detectable in peritoneum in normal mice. In this publication, we show (a) that peritoneal Ly-1 B cells resemble splenic Ly-1 B cells with respect to surface marker expression and functional activity (autoantibody production); (b) that Ly 1 B frequencies in peritoneum are considerably higher than in spleen; and (c) that genetic mechanisms reduce peritoneal Ly-1 B frequencies to minimal levels in SJL-related mice and to below detectability in CBA/N and other mice with the X linked immunodeficiency (Xid). In addition, we show that that peritoneal (and perhaps splenic) Ly-1 B populations demonstrate an unique bias in immunoglobulin commitment. That is, they are selectively enriched for cells that express IgM heavy chains in association with lambda light chains. Thus, as a whole, evidence presented here defines the peritoneum as a tightly regulated lymphocyte compartment that normally houses a large population of mature Ly-1 B cells with distinctive functional properties. PMID- 3084284 TI - Inability of autoimmune mice with the lpr gene to spontaneously produce interleukin 3. AB - A recent report (Palacios, R., Eur. J. Immunol. 1984. 14: 599) indicates that spleen cells from MRL-MpJ-lpr/lpr mice spontaneously produce interleukin 3 (IL 3) and suggests that this lymphokine could be responsible for promoting the lymphoid hyperplasia regulated by the lpr gene. The present study shows that splenocytes from several murine strains bearing the lpr gene do not spontaneously produce IL3. This has been determined by measuring the amount of this lymphokine by a bioassay and by the detection of IL3 mRNA using Northern blot analysis. We suggest that another lymphokine is responsible for growth of lymphocytes regulated by the lpr gene. PMID- 3084285 TI - Immunologic memory to phosphorylcholine (PC). VIII. Expression of the VH-12 gene product in the response to PC-keyhole limpet hemocyanin. AB - Three murine anti-phosphorylcholine (PC) hybridomas with group II-like fine specificity patterns isolated during a memory response to PC-keyhole limpet hemocyanin (KLH) are examined at the molecular level to determine the origins of the VH and VL used by these antibodies. Southern blots of Hind III cut DNA were hybridized with a probe specific for the V1 gene of the T15 VH family. The V1 germ-line configuration is retained in these hybridomas indicating that this gene which encodes the VH gene product expressed by most group I anti-PC hybridomas is not used for antibody production. Southern blots of Eco RI cut DNA hybridized to a probe specific for JH1-JH4 indicated that all three hybridomas PCG1-2, PCG1-3 and PCM-23 share a 5.2-kb rearranged JH band, suggesting utilization of a common VH gene segment. N-terminal amino acid sequence analysis of the heavy chains of two of the hybridoma proteins PCG1-2 and PCG1-3 indicates that they belong to mouse heavy chain subgroup II and are closest in sequence to a VH-12 isotype anti PC hybridoma protein, HPC-104, derived from BALB/c mice suppressed for the T15 idiotype; PCG1-2 and PCG1-3 each differed from HPC-104 at only 1/20 residues. In addition, these proteins have in common a lysine at position 1 which has not been found previously in 203 other heavy chain sequences reported. N-terminal sequences of the light chains of PCG1-2 and PCG1-3 are each shown to differ at only 1/22 residues from V kappa 24, and PCM-23 had previously been shown to use V kappa 8; both of these have been associated previously with heavy chains derived from the V1 gene in anti-PC antibodies. These results indicate that the VH-12 isotype can be used during a normal antibody response to PC and thus that heavy chains derived from both subgroup II and subgroup III (the T15 heavy chain) contribute to the molecular heterogeneity observed in memory responses to PC-KLH. PMID- 3084286 TI - Analysis of immunoglobulins expressing the V kappa 21E and V kappa 21D gene products. Evidence for multigenic control of the expression of VH-VL combinations. AB - The aim of this work was to study the genetic control of VH-VL combined expression. To this end immunoglobulins expressing the V kappa 21E and V kappa 21D gene products were isolated from the normal sera of several inbred strains of mice using a monoclonal antibody that selectively reacts with V kappa 21E and V kappa 21D subgroups. Analysis of the isoelectric focusing (IEF) pattern of the IgG heavy chains of these immunoglobulins obtained from H-2-congeneic mice revealed as expected that Igh-linked loci strongly influence VH-VL combined expression. The IEF pattern of V kappa 21D and V kappa 21E-associated heavy chains isolated from recombinant inbred mouse strains, however, revealed different phenotypes from either parental strains in strains in which both H-2 and Igh loci segregated from the same parent. These data, therefore, strongly suggest that the expression of VH-VL combinations is controlled in part by genetic loci which segregate independently from those linked to H-2 and Igh. PMID- 3084287 TI - Construction of chimeric thymuses in the mouse fetus by in utero surgery. AB - Normal thymuses develop in the coelomic cavity of mice following grafts carried out in utero into embryonic day 16 to 17 fetuses of the third branchial arch region removed from 10-day embryos. The recipients were killed at various times (up to 29 days after birth) and the thymic lobes which developed from the graft were recovered. Microscopical examination and immunocytochemistry revealed that these thymuses developed normally whether the grafts involved syngeneic or allogeneic (between BALB/c and C3H) strain combinations. Two major populations of class II-expressing cells could be recognized by the Ia allotype they expressed: epithelial cells of donor type and accessory cells of host origin. PMID- 3084288 TI - Interferon-gamma induces light chain synthesis in interleukin 2 stimulated human B cells. AB - Human B cells were cultured without added lymphokines, with interleukin 2 (IL2) or interferon-gamma (IFN-gamma) alone, or with a combination of IL2 and IFN gamma. Treatment with IL2 alone induced differentiation of the B cells, as shown by an increase in the number of immunoglobulin (Ig)-containing cells and plaque forming cells, and by a larger amount of Ig secreted into the medium. In most of the induced Ig-containing cells, heavy chains but not light chains were detectable by cytoplasmic staining. Treatment with IFN-gamma alone did not stimulate B cell differentiation. However, a combination of IFN-gamma and IL2 was more effective than IL2 alone in inducing B cell differentiation, as measured by further increases in the number of plaque-forming cells and in total Ig secretion. Furthermore, after treatment with both IL2 and IFN-gamma, most cells that contained cytoplasmic heavy chains also contained cytoplasmic light chains. We conclude that IFN-gamma acts in synergy with IL2 in B cell differentiation by enhancing light chain synthesis, leading to secretion of Ig molecules. PMID- 3084289 TI - In vivo induction of H-2K/D antigens by recombinant interferon-gamma. AB - B10.BR mice received i.v. increasing doses of recombinant interferon-gamma (rIFN gamma) on three consecutive days. Using an immunoperoxidase technique the distribution of H-2K/D antigens was studied in frozen tissue sections of thirteen organs (kidney, liver, pancreas, esophagus, stomach, small intestine, colon, lungs, heart, brain, thymus, lymph node and spleen). Class I antigens were shown to be induced or enhanced in almost every organ after exposure to IFN-gamma. This effect was particularly conspicuous for renal tubular cells, hepatocytes, bronchiolar epithelial cells, gastric mucous cells, thymic cortical lymphocytes and capillary endothelial cells in heart and kidney. Neurons, glial cells, gastric chief and parietal cells, and pancreas cells were not inducible. The findings show that i.v. application of IFN-gamma leads to strong induction or enhancement of major histocompatibility complex class I antigens in a wide variety of tissues. PMID- 3084290 TI - CD2 and CD3 antigens mobilize Ca2+ independently. AB - Antigen-induced stimulation of T cells is mediated via the CD3 antigen receptor (Ti) complex and monoclonal antibodies (mAb) reacting with CD3 and Ti result in rapid intracellular Ca2+ mobilization, followed by monocyte-dependent proliferation. Combinations of mAb to CD2, the sheep red blood cell receptor, also mobilize calcium and induce mitogenesis and purified phytohemagglutinin (PHA) stimulates T cells predominantly by interaction with this molecule. It has been suggested that activation via CD2 requires the presence of CD3 and that the hydrophobic epsilon chain of CD3 is the T cell calcium channel. To investigate this further we have obtained large numbers of natural killer (NK) cells which express CD2 but not CD3 from a patient with a chronic expansion of this lymphocyte subpopulation. It is shown that calcium mobilization can be induced in these cells by mAb to CD2 and purified PHA but not by anti-CD3 mAb. This indicates that calcium mobilization can be induced via the CD2 molecule in NK cells not expressing CD3 and that activation through CD2 is separate from the antigen receptor CD3 pathway. PMID- 3084291 TI - Agonist-induced contractile responses of human bronchial muscle in vitro: effects of Ca2+ removal, La3+ and PY108068. AB - The effects of reducing the extracellular Ca2+ concentration ([Ca2+]0), the effects of La3+ and the dihydropyridine Ca2+ entry blocker PY108068 on contractile responses in human isolated bronchial strips have been compared. Reducing [Ca2+]0 or the presence of La3+ (1 mM) caused a reduction in basal tone, whereas PY108068 (1 microM) had no effect on unstimulated preparations. Response to KCl and A23187 were, in general, more markedly depressed by reducing the entry of extracellular Ca2+, with La3+ or PY108068 than were those to histamine, methacholine and LTD4. The effects of reducing [Ca2+]0, La3+ and PY108068 on responses to the receptor-mediated agents suggest that intracellular Ca2+ may be mobilized upon receptor activation, whereas responses to KCl and A23187 appear to be dependent upon the influx of extracellular Ca2+. More than one source of activator Ca2+ can therefore be involved in the development of contractions in human airway smooth muscle. These findings are in accord with those observed for in vitro airways preparations from experimental animals. PMID- 3084292 TI - Ca2+-induced aortic contraction in normal K+ after exposure to Ca2+- and Mg2+ free solution. AB - Guinea pig and rabbit aortic rings which have been incubated in a Ca2+- and Mg2+ free solution containing ethylene glycol bis-(beta-aminoethyl ether) N,N,N'N' tetraacetic acid (EGTA) responded to addition of Ca2+ in a similar Ca2+ - and Mg2+ -free solution without EGTA by increasing tension gradually at first and then more sharply at Ca2+ concentrations above 2 mM. Prior addition of D 600 (10 or 50 microM) inhibited contractions to low Ca2+ concentrations, but only partially attenuated those to high Ca2+ concentrations. The resulting contraction is thought to represent Ca2+ entry from both voltage-dependent (D 600-sensitive) Ca2+ channels and Na+ -Ca2+ exchange (D 600-insensitive). PMID- 3084294 TI - [2-Arylidene 3,4-dihydro-1 (2H)-naphthalenones with potential platelet anti aggregating activity: synthesis and structural and pharmacologic study]. AB - New 3,4-dihydro-2-arylidene-1-(2H)-naphthalenones derivatives were synthesized and their inhibitory effects in vitro on the arachidonic acid-induced platelet aggregation were evaluated. The 3,4-dihydro-2-[(2,5-dimethoxyphenyl)methylene]-1 (2H)-naphthalenone++ + exhibits the most potent antiaggregating activity; compared with aspirin this compound is three times more active. Its crystal structure has been determined. PMID- 3084293 TI - Copper exchanges and toxicity in the rabbit lens in vitro. AB - Lenses (in vitro) exposed to 10(-4) M Cu for 24 hr gained an excess of Na and lost K. Incubation for 7 days with 10(-5) M Cu had a similar toxic effect. Threonine, which is present in aqueous humor, increased sensitivity of lenses to Cu, and also uptake of 64Cu. Uptake of 64Cu commenced reaching tissue saturation levels in 5 hr at 10(-7) M Cu. At higher concentrations, uptake was greater (1263 X for a 1000-fold rise in concentration from 10(-7) -10(-4) M) and saturation was not seen in this time. Autoradiography of sections of such lenses suggested that accumulation of the 64Cu occurred principally within the region of the cells of the anterior epithelium and capsule and lens bow. Efflux of accumulated 64Cu occurred more rapidly when copper was present in the external media suggesting the presence of 'specific' binding sites for copper. Percentage retention of accumulated 64Cu was greater in lenses loaded in 10(-6) M than 10(-5) M Cu. It is suggested that copper can enter lenses, possibly facilitated by threonine, and can bind to two types of sites: one with a high affinity but low capacity for the metal ion, the other with a lower affinity but larger capacity. The former may be concerned with the physiological roles and normal metabolism of copper and the latter with its toxic actions. PMID- 3084295 TI - Pyruvate utilization by synaptosomes is independent of calcium. AB - The significance of Ca2+ is assessed for the activation of pyruvate by intact nerve terminals (synaptosomes). Titration of glucose-depleted synaptosomes with pyruvate in the presence of either veratridine or uncoupler stimulates respiration in a Ca2+-independent manner. Additionally, the ability of exogenous pyruvate to support the mitochondrial membrane potential in situ is independent of Ca2+. It is concluded that Ca2+ does not regulate pyruvate oxidation in intact synaptosomes. PMID- 3084296 TI - Peptides of postulated inhibin activity. Lack of in vitro inhibin activity of a 94-residue peptide isolated from human seminal plasma, and of a synthetic replicate of its C-terminal 28-residue segment. AB - A 94-residue polypeptide isolated from human seminal plasma and its chemically synthesized C-terminal 28-residue segment were studied in an in vitro inhibin bioassay utilizing rat pituitary cell cultures. Both peptides have previously been claimed to have inhibin activities, and the effects on the secretion and cellular content of gonadotrophins (FSH and LH) were now assessed in the in vitro assay. No inhibition was found. After 72 h of culture, both the cellular content and the spontaneous as well as the LHRH-stimulated release of bioactive or immunoactive FSH and LH remained unaffected. Similarly, no effects were found on the storage and/or release of prolactin, growth hormone, or thyrotropin. We conclude that both the native 94-residue peptide and the synthetic replicate of its C-terminal 28-residue segment, do not influence the pituitary FSH secretion when assessed in this in vitro system. PMID- 3084297 TI - Amino-terminal heterogeneity of E. coli TEM-beta-lactamase secreted from Bacillus subtilis. AB - E. coli TEM-beta-lactamase, secreted from Bacillus subtilis after transformation with three different hybrid plasmids, was purified and subjected to direct amino terminal sequence analysis. The results show that the signal sequence cleavage site varies depending on the hybrid plasmid construction and cannot be exactly predicted from the DNA sequences. The results are of general interest if recombinant DNA technology is used to synthesize, e.g. pharmaceutical products where the preservation of the authentic amino-terminal structure is highly desirable. PMID- 3084298 TI - Localization of talin in skeletal and cardiac muscles. AB - Antibodies to talin and vinculin were used for localization of these proteins in skeletal and cardiac muscles by the indirect immunofluorescence method. We have found that talin is localized in intercalated discs of cardiac muscle and in costameres of skeletal and cardiac muscles. It is suggested that in striated muscles talin and vinculin play an important role in interactions between actin filaments and membranes. PMID- 3084299 TI - Inactivation of basal glycogen synthase by glucagon and epinephrine in hepatocytes from fed rats. AB - Glucagon and epinephrine promote the inactivation of basal glycogen synthase in hepatocytes isolated from fed rats. However, this effect is only observable when the activation state of glycogen synthase is measured using the low glucose-6 P/high glucose-6-P activity ratio assay. This inactivation is the consequence of an increase in the kinetic parameters (S0.5 for UDP-glucose and M0.5 for glucose 6-P) of the enzyme. Therefore, this work demonstrates these hormones are also able to control glycogen synthase from fed animals. PMID- 3084300 TI - Long-acting gonadotropin hormone-releasing hormone analog used to treat uteri. AB - Because the size of leiomyomata uteri often decreases significantly after menopause, the authors elected to employ a long-acting gonadotropin hormone releasing hormone analog (GnRH-alpha) (imbzl-D-His6-Pro9-Net-GnRH) to create a state of pseudomenopause in six patients with leiomyomata uteri diagnosed on the basis of pelvic examination and confirmed by pelvic ultrasonography. Patients received daily, subcutaneous injections of GnRH-alpha (4 micrograms X kg-1 X 24 hour-1) for 6 months. Uterine size (13.8 +/- 4 weeks [mean +/- standard deviation (SD), n = 6]) was determined by pelvic examination and uterine volume (533.9 +/- 394 ml [mean +/- SD, n = 6]) was determined by pelvic ultrasonography before medical therapy was begun. They observed a decrease in uterine size by pelvic examination within 4 weeks of the initiation of therapy, and all patients experienced a decrease in uterine size (9.5 +/- 4 weeks [mean +/- SD, n = 6]) (P less than 0.05) within 8 weeks of initiation of therapy. After 6 months of therapy, uterine size was 229.5 +/- 145 ml (mean +/- SD, n = 6). During treatment, plasma estrogen concentrations were assessed intermittently (every 1 to 4 weeks) and remained less than 4 pg X ml-1 throughout the period of therapy. All six patients have discontinued therapy. There has been no increase in uterine size in these patients for a period from 3 to 7 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084301 TI - Danazol inhibits steroidogenesis by the human ovary in vivo. AB - Gonadotropins, estradiol (E2), and the steroid precursors of ovarian estrogen secretion were examined in women on danazol to clarify actions of the medication on hypothalamic-pituitary-ovarian function. Follicle-stimulating hormone was not altered acutely after a single maximal dose or chronically during therapy, whereas a slight but significant increase in luteinizing hormone was noted during the 6 months of treatment. During danazol treatment, there was a blunted response of E2 to injections of human menopausal gonadotropins. The progestin and androgen precursors of E2 were reduced, with the exception of 17-hydroxypregnenolone, which was significantly increased. This 17-hydroxylase enzyme block persisted in spite of dexamethasone suppression of adrenal function. Therefore, the reduced ovarian secretion of E2 in women receiving danazol is due in part to reductions of ovarian precursor steroids for E2 synthesis, consequent to a direct ovarian action of the medication. PMID- 3084302 TI - Ultrastructural characterization of human granulosa cells in stimulated cycles: correlation with oocyte fertilizability. AB - The fine structure of human granulosa cells (GC) obtained in the course of an in vitro fertilization procedure was correlated with oocyte fertilizability. The investigation was performed by light-microscopic and electron-microscopic examination of ultrathin sections and replicas of freeze-fractured material. GC associated with nonfertilizable oocytes (group I) had significantly smaller cell areas, tended to be tightly packed, and exhibited abundant intercellular gap junctions and adherence junctions. Multiple structural variations of cytoplasmic organelles were observed in comparison to cells associated with fertilizable oocytes (group II). Cells in group II tended to be widely dispersed, frequently contained interiorized gap junctional elements (annular junctions), and showed morphologic correlates of high steroidogenic activity. Structural dissimilarities between groups I and II were not consistently related to follicle size, as determined by volume of aspirated follicular fluid. In view of the sequential ultrastructural changes known to occur during follicular maturation and ovulation, it is concluded that GCs related to nonfertilizable oocytes were lacking structural correlates of luteinizing hormone/human chorionic gonadotropin responsiveness. PMID- 3084303 TI - Seminal plasma transferrin and seminiferous tubular dysfunction. AB - Seminal plasma transferrin levels were assayed in 158 random semen samples collected from normospermic, oligospermic, and azoospermic men, and their relationships with seminal characteristics, sperm fertilizing capacity as assessed by the zona-free hamster ova penetration assay, and serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) were evaluated. The concentrations of seminal plasma transferrin in azoospermic, oligospermic and postvasectomy samples were significantly lower than those in normospermic samples. Seminal plasma transferrin concentrations were similar in azoospermia due to obstruction of the reproductive tract or damage to the germinal epithelium. No significant difference in seminal plasma transferrin concentrations was observed in the groups of subjects with normal and elevated FSH or normal and elevated LH. A positive correlation was observed between seminal plasma transferrin concentration and sperm density and between total semen transferrin content and the total number of sperm in the ejaculate. There were no significant correlations between seminal plasma transferrin concentration and sperm motility, percent normal sperm, sperm fertilizing capacity, and serum FSH or LH concentration. The results indicate that seminal plasma transferrin is not a useful marker for Sertoli cell or seminiferous tubular dysfunction. In addition, it is doubtful that measurement of seminal plasma transferrin will yield additional information regarding the fertility potential of semen samples. PMID- 3084304 TI - Hormonal parameters in incidental varicoceles and those causing infertility. AB - The gonadotropin responses to a 4-hour infusion of gonadotropin-releasing hormone (GnRH), the prolactin (PRL) responses to a bolus injection of thyrotropin releasing hormone (TRH), and seminal plasma dihydrotestosterone (DHT) levels were assessed before and 6 to 12 months after varicocelectomy was performed in 56 infertile men with varicoceles and sperm densities less than 30 X 10(6)/ml. The men were divided into four groups, determined by their sperm densities and hormonal parameters. Groups I (18 men) and II (12 men) had sperm densities less than 10 X 10(6)/ml, and groups III (16 men) and IV (10 men) had sperm densities of 11 to 30 X 10(6)/ml. The men from groups I and III had excessive preoperative gonadotropin and PRL responses, and lower-than-normal seminal plasma DHT levels. The men in groups II and IV had normal hormonal values. After operation, 12 of the men from group I and 11 from group II had improvements in seminal and hormonal parameters. The other men in these two groups and all of the men in groups II and IV had no changes in seminal and hormonal parameters after operation. This study indicates that an assessment of these hormonal parameters may be useful in predicting which men with varicoceles are likely to have an improvement in sperm density after varicocele repair. PMID- 3084305 TI - Constant ovulation on the side of an occluded tube treated with human menopausal gonadotropin. AB - We have presented the case of a woman with unilateral occlusion of a tube ovulated permanently on the same side. The other ovary and tube were intact. To overcome this problem, we gave full menotropic treatment to induce super ovulation, and the patient became pregnant in the second treatment cycle. We think medical treatment should be attempted before paradoxical oophorectomy is contemplated in women with unilateral occlusion who cannot become pregnant. PMID- 3084306 TI - [Changes in the mass transfer of blood gases in hypoxia during infusion of and emulsion of perfluorocarbons]. AB - Systemic hemodynamic parameters, physico-chemical homeostasis and blood rheology were studied using the model of anemic hypoxia after substitution of the blood with salt solution exceeding the blood loss, with or without additional administration of perfluorocarbon (PFC) emulsion. The data obtained suggest that physiological reactions of O2 deficiency compensation in anemic hypoxia (increased O2 extraction, improved heart performance) can be substantially improved if the PFC emulsion is present in the blood flow as the PFC seems to enhance the mass transfer of blood gases. PMID- 3084307 TI - [Effects of transient or occult hyperprolactinemia on luteal function]. AB - It is well known that the luteal function in the patients with hyperprolactinemia is much suppressed by high level of serum prolactin. Present study was performed to investigate whether the luteal function in the patients with transient or occulted hyperprolactinemia was affected by the transient increase of serum prolactin level. The circadian changes of serum FSH, LH, prolactin, estrone, estradiol and progesterone levels were examined in seven cases of the transient or occulted hyperprolactinemia whose BBT charts showed biphasic patterns. Serum prolactin levels of these patients were less than 25 ng/ml at daytime and more than 150 ng/ml at 30 minutes after the administration of 500 micrograms of TRH. Blood samplings were taken every two hours through an intravenous indwelling catheter without any disturbances. All of the patients had their breakfast at 7 to 8, lunch at 11 to 12 and dinner at 17 to 18 o'clock and slept from 22 until 6 in the next morning. Serum FSH, LH, prolactin, estrone, estradiol and progesterone levels were determined by RIA and the circadian changes of these hormones were analysed. Then, 5 mg of bromocriptine was administered every day to these patients for more than 30 days and the duration of the luteal phase and the mid-luteal serum estradiol and progesterone levels for the indicators of the luteal function were examined before and after the administration of bromocriptine. The circadian changes of serum prolactin levels in the patients showed significant increase during both daytime and night compared to those of the control (p less than 0.005, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084308 TI - [The effect of synthetic chicken LH-RH on the release of LH and FSH and ovulation in rats (a comparative study of synthetic mammalian LH-RH and chicken LH-RH)]. AB - Recently, Miyamoto et al and King et al, independently isolated chicken LH-RH and determined its chemical structure as [Gln8] LH-RH. In this report, the in vivo effect of synthetic chicken LH-RH on the release of LH and FSH and ovulation in rats was investigated. A single i.v. injection of chicken LH-RH, as well as mammalian LH-RH, induced a significant increase of plasma LH levels at 15 min after injection in adult male rats. Plasma LH levels then declined at 30 min to 60 min and returned to basal levels at 120 min. The biological potency of chicken LH-RH estimated from plasma LH levels at 15 min after injection in adult male rats by parallel line assay was 4.1% of that of mammalian LH-RH. It was likely that the activity of chicken LH was shorter in duration on the LH secretion as compared with that of mammalian LH-RH because of quickly decreased plasma LH levels. Plasma FSH levels were also increased, but the increment of FSH was not so obvious as compared with that of LH. Plasma FSH levels reached a plateau at 15 min and did not return to basal levels at 120 min in either the chicken LH-RH injection groups or the mammalian LH-RH injection groups. The chicken LH-RH was able to induce an increase of plasma LH and FSH and ovulation in pentobarbital blocked, proestrous female rats. The biological potency of chicken LH-RH estimated from plasma LH levels at 15 min after injection in pentobarbital blocked, proestrous female rats was 2.2% that of mammalian LH-RH. The ovulation inducing potency of chicken LH-RH estimated from ED50 was about 2.1% of that of mammalian LH-RH. It is noteworthy that chicken LH-RH has a LH and FSH releasing and ovulation inducing-activity on rats in vivo, but its biological potency is weaker and of shorter duration compared with that of mammalian LH-RH, although the chemical structure of chicken LH-RH is different from that of mammalian LH RH. PMID- 3084309 TI - [An increase in calcitonin levels in the thyroid gland of infant rats following parathyroidectomy]. AB - It is well known that serum calcitonin (CT) levels in infantile rats are higher than those in adult rats. In the present experiment, the effects of parathyroidectomy or calcium administration on serum calcitonin levels were observed in suckling rats. Bilateral parathyroidectomy (Px) on 3-, 5-, 7-, 8- or 14-day-old Wistar-Imamichi female rats was performed surgically under a dissecting microscope. Ether anesthesia was used. In the first experiment, the Px rats of various age groups were killed 1 week after the operation. In the second experiment, time course effects of Px on one-week-old rats were observed 1, 2 or 3 weeks after the operation. CT in the serum and thyroid extracts (0.001N HCl) was measured using radioimmunoassay kits for human CT. Serum Ca was measured by the OCPC method and serum inorganic phosphates was measured by the Takahashi method. Serum calcium levels showed a significant decrease 1 week after Px in all age groups. In these rats, serum CT levels showed a slight increase or no changes, and a significant increase in CT concentrations in the thyroid gland was observed in all age groups. Moreover, the increase in CT contents in the thyroid gland became larger 3 weeks after Px in rats operated on at one week of age. Thyroid extract containing 70 pg immunoreactive CT was effective in decreasing 1.22 mg/100 ml serum calcium at 15 min after i.v. injection in a bioassay system in which a dose response curve of human calcitonin was used as standards. Acute s.c. injection of CaCl2 solution resulted in a significant increase in serum CT levels 15 and 30 min later in intact 2- and 3-week-old rats, whereas no significant change in serum CT levels was observed in one-week-old intact rats. Three and 15 min after s.c. injection of Na2EDTA, serum Ca levels decreased markedly, but thyroidal CT contents tended to increase 3 and 5 min after the injection. The results indicated that parathyroidectomy in infantile rats induces a marked increase in biologically active calcitonin in the thyroid gland, inspite of the significant decrease of serum Ca levels. PMID- 3084310 TI - [The effect of synthetic human pancreatic growth hormone-releasing factor (hpGRF 44) on serum growth hormone response in normal and obese subjects]. AB - Synthetic human pancreatic growth hormone-releasing factor (hpGRF-44) was given by i.v. bolus injection to 15 normal non-obese and 32 obese subjects who were divided into two groups according to their ages--group A: young subjects, 20-50 yrs., and group B: old subjects, more than 60 yrs. In normal subjects, hpGRF-44 had no effect on the secretion of PRL, TSH, LH, FSH, IRI and cortisol. hpGRF-44 stimulated GH secretion selectively. However, the serum GH responses were different between the young and old groups, the peak GH levels being significantly higher in the young group than in the old group (20.1 +/- 4.2 vs. 7.5 +/- 1.6 ng/ml; group A vs. B; p less than 0.05). At the doses of 0.5, 1.0, 2.0 and 4.0 micrograms/kg B.W., the serum GH responses were similar in an individual subject. In young obese subjects, the peak GH levels to hgGRF-44, 1.0 microgram/kg B.W. were significantly lower than those in young normal subjects (4.3 +/- 0.6 vs. 20.1 +/- 4.2 ng/ml; obese vs. normal; p less than 0.01). In old subjects, the peak GH levels to hpGRF-44, 1.0 microgram/kg B.W. were similarly diminished in both normal and obese subjects. However, the integrated response of GH was significantly lower in obese subjects than in normal subjects (405.9 +/- 58.7 vs. 755.9 +/- 134.2 ng X min/ml; obese vs. normal; p less than 0.05). In 5 young obese subjects, regular insulin (RI) injection (0.15 U/kg B.W.) and arginine drip infusion (0.5 g/kg B.W.) alone, and simultaneous injection of hpGRF 44, 1.0 microgram/kg B.W. and RI, 0.15 U/kg B.W. were done. In these subjects, GH responses to RI or arginine infusion were diminished as in the case of hpGRF-44 administration, whereas the peak GH levels were higher in the RI stimulation. The combination of hpGRF-44 and RI partially restored GH response. (peak GH levels; 14.6 +/- 0.8 ng/ml). These results confirm the age difference of serum GH response to hpGRF-44 and also indicate that obese subjects show low or no response to hpGRF-44 administration. The fact that insulin hypoglycemia induced larger serum GH response that hpGRF-44 in obese subjects may suggest the existence of GH-releasing substances other than hpGRF-44. PMID- 3084311 TI - Reasonable cost and efficiency are the goals. PMID- 3084312 TI - [Cryotolerance of Neisseria gonorrhoeae]. PMID- 3084313 TI - [En pailettes d'or maculopathy caused by carotinoid therapy]. PMID- 3084314 TI - [Secondary failure of oral antidiabetics. Value of intravenous insulin infusions]. AB - A temporary strict blood glucose control was achieved by means of intravenous insulin infusion in 37 non insulin-dependent diabetic patients with secondary drug failure to reinduce the efficacy of oral hypoglycemic agents. This procedure was successful in 18 patients (48.6%) resulting in better glycemic response to oral hypoglycemic agents. Results remained identical 6 and 12 months later. This improvement does not seem related to an increase in insulin secretion as urinary C-peptide and basal and glucagon-stimulated plasma C-peptide were identical before and after insulin infusion. We suggest that a decrease in insulin resistance, not tested in this study, may explain the beneficial effect or normoglycemia in our patients. PMID- 3084315 TI - Effect of glibenclamide in insulin-treated diabetic patients with a residual insulin secretion. AB - We have studied the effect of the combination of a sulfonylurea (Hb 420 or glibenclamide) with insulin in 22 type II diabetic patients, treated with insulin and with residual insulin secretion (fasting plasma C peptide level greater than 0.2 pmol/ml). After a 3 week run-in period, the patients received either glibenclamide (7 mg of Hb 420 before breakfast and 3.5 mg before supper) or placebo in double blind fashion. Clinical and biological parameters (body weight, number of hypoglycemic episodes, daily insulin dose, fasting and postprandial glucose and C peptide levels after a standard meal) were collected during the basal (run-in) period and after 8 and 16 weeks of treatment. In the glibenclamide group, a significant increase in the number of hypoglycemic episodes was observed in spite of a 8 to 10% reduction in insulin requirements. A 18% reduction of both fasting and postprandial plasma glucose levels was found after 8 and 16 weeks of glibenclamide therapy. Concomitantly, a 35% increase of fasting and postprandial plasma C peptide levels occurred. The data suggest that the use of combined sulfonylurea and insulin therapy may be beneficial to type II diabetic patients with residual insulin secretion and poor glycemic control under insulin therapy alone. PMID- 3084316 TI - Use of carbamazepine in acute psychosis: a controlled study. AB - A randomized double-blind study was performed to compare the therapeutic effects of lithium and carbamazepine (CBZ) each administered in combination with chlorpromazine (CPZ) for 3 weeks in women with acute psychosis. Thirty patients were studied. The initial dose was 1200 mg/day for CBZ and 900 mg/day for lithium, and it was subsequently modified according to plasma levels and clinical indications. The dose of CPZ was free and depended on the severity of symptomatology. Both treatments produced a significant improvement in psychotic symptoms without significant differences between the treatment groups. Also, as regards tolerability no clinically relevant differences were found between the two groups. During the first week of treatment the CPZ dose required in the CBZ group was significantly lower than that administered to the lithium group, indicating that CBZ had a greater sedative action; however, this difference decreased as treatment continued. These results confirm that CBZ is a valid alternative to lithium in the treatment of acute psychosis. PMID- 3084317 TI - Sites of prostaglandin E2 (PGE2) synthesis along the rabbit nephron. AB - The purpose of this study was to establish whether the nephron segments recognized as PGE2 target sites in the rabbit, i.e. the proximal tubule, the thick ascending limb and the collecting tubule, are also sites of PGE2 production. We therefore developed a microimmunoassay sensitive enough to allow the measurement of PGE2 on microdissected tubular segments about 1 mm in length. Under the conditions used (30 min incubation at 20 degrees C), a basal rate of PGE2 production was measured in the cortical (CCT) and medullary portions of the collecting tubule, as could be expected. In the presence of 10(-4) M sodium arachidonate, it was shown that: (1) The thin descending limb (TDL) is also an active site of PGE2 formation. When expressed per mm tubule length the amounts formed were lower in TDL than in CCT (14.1 +/- 2.7 SE pg/mm, n = 5, vs. 93.5 +/- 10.7, n = 8). They were quite comparable, however, when expressed per microgram total proteins (0.70 ng in TDL vs 0.6 in CCT). (2) A slight PGE2 production was noted in the connecting tubule but it was likely due to contamination by adjacent CCT cells. (3) In the other nephron segments, only negligible amounts of PGE2 were formed, which are probably of no physiological significance. PMID- 3084318 TI - The choice of a model for studying the hypothalamus-pituitary interactions in vitro. AB - Comparative studies on the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (Prl) by the whole pituitary, pituitary plus hypothalamus and pituitary-hypothalamus complex (PHC) were undertaken to choose an appropriate model for studying the hypothalamus-pituitary interactions in vitro and to relate the importance of the intact neural connections between pituitary and hypothalamus on hypothalamus-pituitary interactions. Also the effect of including dopamine (DA) at 1 X 10(-7) mol/1 in these different in vitro systems on the release of LH, FSH and Prl was investigated. The pituitary released increasing amounts of LH and FSH at 2, 4 and 6 h but the amount of Prl released remained unchanged. The rates of release of LH, FSH and Prl by the pituitary were different and were characteristic of each hormone. Co-incubation of pituitary with hypothalamus stimulated the release of LH and FSH but inhibited the release of Prl. Pituitary-hypothalamus complex behaved almost identical to behaved almost identical to pituitary plus hypothalamus system. Inclusion of 1 X 10(-7) M DA in the incubation medium stimulated the release of LH (80%) but inhibited the release of Prl (71%) by PHC. FSH was unaffected. DA had no significant effect on the release of LH, FSH and Prl by pituitary and pituitary plus hypothalamus systems. It is suggested that PHC is the system of choice for studying hypothalamus-pituitary interactions in vitro. PMID- 3084319 TI - Subcellular fractionation of the human corpus luteum: distribution of GnRH agonist binding sites. AB - We have investigated the subcellular localization of GnRH agonist (GnRHA) binding sites in the human corpus luteum. Corpora lutea (CL) were obtained from 13 women undergoing laparotomy during the luteal phase of the menstrual cycle. CL homogenates were subjected to subcellular fractionation by either differential rate centrifugation or by sucrose density gradient fractionation with or without digitonin perturbation. Fractions were then assayed for a number of marker activities characteristic of the major intracellular organelles and cell-surface membranes, and for specific binding of [125I]GnRHA. Specific binding of [125I]GnRH agonist was greatest in regions of the gradient (density, 1.12-1.15 g/cm3) enriched in cell-surface and endoplasmic reticulum membrane markers. Little or no GnRHA binding was associated with fractions enriched in nuclei, mitochondria or lysosomes. Digitonin treatment demonstrated that the majority of GnRHA binding sites were associated with luteal cell plasma-membranes: however, some GnRHA binding was also associated with endoplasmic reticulum. These results indicate that: (i) human luteal GnRHA binding sites were not associated with lysosomal proteases, (ii) a significant fraction (59%) of GnRHA binding sites was localised on the luteal cell-surface membrane. Specific GnRHA binding to both cell-surface and endoplasmic reticulum membranes may indicate an extensive turnover of membrane binding sites. PMID- 3084320 TI - Influence of the calcium ionophores A23187 and X537A on calcitonin secretion from the isolated perfused porcine thyroid. AB - The present study examined the influence of the calcium ionophores A23187 and X537A on the calcitonin (CT) secretory process. The isolated perfused porcine thyroid was used to evaluate ionophore effects on CT secretion and thyroid slices were used to measure 45Ca uptake. Both A23187 and X537A enhanced the rate of CT release from the perfused thyroid. A23187 at a concentration of 19 microM (10 micrograms/ml) produced a maximal increase in CT secretion of 325% above control levels. X537A at a concentration of 16 microM (10 micrograms/ml) produced a peak rise in CT release of approximately 2000% over control levels. The CT secretory response to A23187 was found to be completely calcium dependent; however, the secretory response to X537A was partially, but not completely dependent upon the presence of perfusate calcium. The results demonstrate that these calcium ionophores are very potent CT secretagogues which vary considerably in their calcium dependency. PMID- 3084321 TI - Case mix system provides basis for KGH's resource management. PMID- 3084322 TI - Combined care nursing caters to parents' needs. PMID- 3084324 TI - The effects of sorbinil on peripheral nerve conduction velocity, polyol concentrations and morphology in the streptozotocin-diabetic rat. AB - This study examined the effects of an aldose reductase inhibitor, Sorbinil, on neuropathy over a 6-month period in streptozotocin-diabetic rats. Sorbinil treatment prevented the 10-fold increase in nerve sorbitol found with diabetes. It produced a 60% improvement in tibial nerve motor conduction velocity after 6 months. Morphometric profiles of nerves were also normalized. Axon area was reduced by 14% in untreated diabetic rats compared to age-matched controls, whereas Sorbinil-treated animals showed normal age-related axon growth. Myelin area was increased by 28% in untreated diabetic animals, but was the same as age matched controls with Sorbinil treatment. Nerve myo-inositol levels were reduced by 45% after three months of untreated diabetes, but were normal after six months. Sorbinil treatment tended to restore myo-inositol levels toward normal over the shorter time period. It was concluded that axon growth retardation is the most likely cause of the conduction deficit seen in long-term experimental diabetes. PMID- 3084323 TI - Diabetic ketoacidosis: current views on pathogenesis and treatment. PMID- 3084325 TI - Protection by zinc against acetaminophen induced hepatotoxicity in mice. AB - The purpose of this investigation was to assess protection by zinc against acetaminophen induced hepatotoxicity and to evaluate possible mechanisms of protection. Mice were treated with zinc (3 mg/kg, ip) or saline (ip) 48 and 24 hr before and sacrificed 12 hr after acetaminophen administration (375, 500, or 750 mg/kg, po). Liver toxicity was then assessed by histological examination. The incidence of hepatotoxicity was significantly less at 375 and 500 mg/kg of acetaminophen in zinc treated animals. The same dosage of zinc was not hepatoprotective when given 1 hr after acetaminophen. Mice were also treated with 1 to 10 mg/kg of zinc (ip) 48 and 24 hr prior to sacrifice, and metallothionein, cytochrome P-450, glutathione, and UDP-glucuronosyl transferase (GT) were determined in the liver. Metallothionein and UDP-GT were increased and P-450 and glutathione decreased at the higher dosages of zinc; however, only metallothionein was significantly changed at the dosage of zinc (3 mg/kg) used in the hepatoprotection experiments. Further, mice were similarly treated with 3 mg/kg of zinc before administration of 375 mg/kg of [3H]acetaminophen (po) and the amount of acetaminophen and acetaminophen bound to metallothionein were determined in the liver for 0.5 to 24 hr. In addition, after 6 hr the subcellular distribution and covalent binding to protein of acetaminophen were also determined. Zinc treatment had no significant effect in any of the above determinations. These results indicate that zinc protects against acetaminophen induced hepatotoxicity and that the observed protection is probably due to an induced biochemical change, but it is apparently not the result of any of the commonly invoked mechanisms. PMID- 3084326 TI - Ingestion of soil contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters hepatic enzyme activities in rats. AB - Female rats were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in either corn oil or contaminated soil from the Minker site in Missouri. Eight doses ranging from 0.015 to 5 micrograms TCDD/kg were used in the corn oil group; the range was 0.015 to 5.5 micrograms TCDD/kg in the TCDD-contaminated soil group. Rats in a third group were given equal amounts of soil uncontaminated with TCDD. No acute toxicity or effects on body weight gain were observed at these doses. In general, equivalent doses of TCDD in corn oil or TCDD in soil produced similar increases in hepatic aryl hydrocarbon hydroxylase activity (AHH) and UDP glucuronyltransferase activity although effects were slightly greater in the TCDD corn oil groups. In the corn oil groups, the induction of AHH ranged from about 30-fold at the highest dose to twofold at the lowest dose studied. TCDD also caused an increase in cytochrome P-450 concentration and a shift in spectral peak from 450 to 448 nm. There was no effect of TCDD on ethylmorphine N-demethylase, consistent with previous reports. Liver concentrations of TCDD (mean +/- SD) in the 5-micrograms/kg groups were 40.8 +/- 6.3 ppb in the TCDD corn oil group and 20.3 +/- 12.9 ppb in the TCDD-contaminated soil group. Our results suggest that the bioavailability of TCDD in soil in rats is approximately 50%. Therefore, ingestional exposure to TCDD-contaminated soil may constitute a significant health hazard in view of its extremely high toxicity and relatively high bioavailability. PMID- 3084327 TI - An investigation of metaldehyde and acetaldehyde toxicities in dogs. AB - Acetaldehyde has been reported, but has not been proven, to be the toxic entity resulting from metaldehyde ingestion. To investigate this, male dogs were given a single dose of 600 mg metaldehyde or acetaldehyde/kg of body wt via stomach tube. Clinical signs were monitored, and plasma and urine were assayed for metaldehyde and acetaldehyde. Vomiting occurred less often and in a significantly lower number of metaldehyde-dosed dogs than in acetaldehyde-dosed dogs. Ataxia and tremors occurred significantly more often in metaldehyde-dosed dogs than in acetaldehyde-dosed dogs. Acetaldehyde was not detected in the plasma or urine of metaldehyde-dosed dogs, however, it was found in a sample of vomitus from one of the metaldehyde-dosed dogs. Metaldehyde was found in plasma and urine of metaldehyde-dosed dogs. Urinary excretion of metaldehyde from the metaldehyde dosed dogs was less than 1%. Urinary excretion of acetaldehyde from acetaldehyde dosed dogs was essentially nonexistent. Metaldehyde has a larger role in the mechanism of metaldehyde toxicity than previously thought. While acetaldehyde appeared to be of significantly lesser importance, we could not eliminate it as a factor in metaldehyde toxicity in dogs. PMID- 3084328 TI - Subchronic oral toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the guinea pig: comparisons with a PCB-containing transformer fluid pyrolysate. AB - In contrast to the well-characterized acute toxicity of the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in the guinea pig, the effects of prolonged po exposure in this species are unknown. The present report describes the results of administration to guinea pigs of 2,3,7,8-TCDD in the feed at levels of 0, 2, 10, 76, or 430 ppt for up to 90 days. Additional aims were to examine recovery following prolonged 2,3,7,8-TCDD exposure in the guinea pig and to generate data to facilitate comparison of the previously reported toxicity of a transformer fluid pyrolysate with that of pure 2,3,7,8-TCDD. Animals receiving 430 ppt 2,3,7,8-TCDD exhibited body weight loss, thymic atrophy, liver enlargement, and 60% mortality by Day 46 (males) and by Day 60 (females), when surviving animals in this group were sacrificed. Total 2,3,7,8 TCDD consumption was approximately 1.3 and 1.9 micrograms/kg, respectively. Animals receiving 76 ppt 2,3,7,8-TCDD for 90 days (total 0.44 microgram/kg) exhibited a decreased rate of body weight gain and increased relative (to body) liver weights. Male animals also displayed a reduction in relative thymus weights and elevated serum triglycerides, while females exhibited hepatocellular cytoplasmic inclusion bodies and lowered serum alanine aminotransferase activities. Toxic effects were generally similar to those observed after acute 2,3,7,8-TCDD administration. No dose-related alterations were seen in animals receiving either 10 ppt (total 0.06 micrograms/kg) or 2 ppt (total 0.01 micrograms/kg) for 90 days, establishing a no-observed-effect level of approximately 0.65 ng 2,3,7,8-TCDD/kg/day. In the recovery study, groups of guinea pigs were administered 430 ppt 2,3,7,8-TCDD for 11, 21, or 35 days and then allowed to recover for an additional 79, 69, or 55 days, respectively. Treatment-related mortality in each group was 0, 10, and 70%, respectively, by Day 90. An effective LD50 of 0.8 microgram 2,3,7,8-TCDD/kg for prolonged exposure was calculated on the basis of these results, a value lower than those previously reported from this laboratory for acute exposure. The results also suggested a possible lowering of the body weight "set point" following 2,3,7,8-TCDD exposure. Comparison of the present findings with those previously reported for a transformer fluid pyrolysate containing a mixture of polychlorinated aromatic species indicated both a greater variety of toxic effects and flatter dose response relationships for the pyrolysate in the guinea pig. PMID- 3084329 TI - A comparative study of the pharmacokinetics of carbon tetrachloride in the rat following repeated inhalation exposures of 8 and 11.5 hr/day. AB - To evaluate whether exposure to inhaled vapors for periods longer than 8 hr/day could affect the rates and routes of elimination, male Sprague-Dawley rats were repeatedly exposed to 100 ppm of radiolabeled carbon tetrachloride (14CCl4) in a closed-loop chamber. One group was exposed for 8 hr/day for 5 days and another group for 11.5 hr/day for 4 days. Two other groups were exposed for either 8 hr/day for 10 of 12 consecutive days or 11.5 hr/day for 7 of 10 days. The elimination of 14C activity was measured in the expired air, urine, and feces for up to 100 hr following exposure and the pharmacokinetic parameters were determined. Following 2 weeks of exposure to the 8-hr/day schedule, 14CCl4 in the breath and 14C activity in the feces comprised 45 and 48% of the total 14C excreted, respectively. Following 2 weeks of exposure to the 11.5-hr/day schedule, the values were 32 and 62%, respectively, indicating that repeated exposure to the longer schedule altered the route of elimination of CCl4. Regardless of the period of exposure, less than 8% of the inhaled 14CCl4 was excreted in the urine and less than 2% was exhaled in the breath as the 14CO2 metabolite. Approximately 97-98% of the 14C activity in the expired air was 14CCl4. The quantities of 14C noted in the feces and urine suggest that more than 60% of the inhaled CCl4 was metabolized. Elimination of 14CCl4 and 14CO2 in the breath followed a two-compartment, first-order pharmacokinetic model (r2 = 0.98). For rats exposed 8 hr/day and 11.5 hr/day for 2 weeks, the average half-lives for elimination of 14CCl4 in the breath for the fast (alpha) and slow (beta) phases averaged 96 and 455 min, and 89 and 568 min, respectively. The average alpha and beta half-lives for elimination of 14CO2 in the breath of rats exposed to the 11.5-hr/day schedule were 455 and 1824 min, and these were significantly longer than for the 8-hr/day groups, 305 and 829 min. The longer half-lives of elimination for 14CO2 and 14CCl4 which were observed for the groups exposed to the 11.5-hr/day schedule suggest that the 3.5 additional hr of daily exposure places a relatively greater percentage of the absorbed dose into poorly perfused lipophilic depots such as the fat.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3084330 TI - The activities of the advisory dentist in the long-term care facility. PMID- 3084331 TI - [Enteral feeding: level and modalities of energy intake?]. PMID- 3084333 TI - Effects of mast cell inhibition on plasma and aortic content of lipids, hexosamine, and hydroxyproline in rats. Role of thyroid gland. AB - Twenty-one-day-old rats were treated with mast cell inhibitors for four weeks. Some of the rats were thyroidectomized in the beginning of the experiment. Mast cell impairment decreased plasma cholesterol and increased plasma triglyceride levels; in aorta, there was a decrease in total protein, hexosamine and hydroxyproline levels, while triglyceride concentration increased and total cholesterol did not change. In thyroidectomized rats, mast cell impairment led to decreased plasma cholesterol and aortic triglyceride content, increased aortic hexosamine and hydroxyproline levels and did not change plasma triglycerides, aortic total cholesterol and total protein content. It was concluded that some effects of mast cell inhibition on arterial wall metabolism are mediated through the thyroid gland. PMID- 3084332 TI - [Continuous ambulatory enteral feeding in hospitalized adults: prospective experience in 98 patients]. AB - The goal of this study, which describes a personal technique of continuous enteral nutrition (CEN) in hospitalized adults on an ambulatory basis, was: to prospectively evaluate, over a 2-year period, its efficacy and tolerance in 98 patients requiring CEN for at least 15 days; to compare its efficacy and tolerance with those of conventional non-ambulatory CEN on a prospectively randomized basis in 16 patients. Ambulatory CEN was given at the rate of 35-45 kcal/kg/d (lipids: 35 p. 100; carbohydrates: 45 p. 100); during day-time, a portable system, including pump, tubes and low-viscosity nutrient solutions, allowed ambulation. Ninety-eight consecutive patients with a minimal level of physical autonomy were treated for intestinal (n = 47), pancreatic (n = 20), esophagogastric (n = 17) diseases, or for malnutrition of other causes for an average of 38 days (15 to 141). The average weight gain (m +/- SD) was 1.2 +/- 5.5 p. 100 of ideal body weight (IBW) and the average nitrogen gain was 0.7 +/- 3.8 g/24 h; weight gain proved significantly lower in patients with inflammatory bowel disease receiving steroids. The clinical tolerance proved excellent, except for 5 cases of transient diarrhea and 9 cases of reposition of the nasogastric tube. A decrease in cholesterolemia below 3.9 mmol/l was noted in 25 p. 100 of patients during CEN. No significant difference between ambulatory and non ambulatory CEN was observed in terms of evolution of body weight and other anthropometric variables, nitrogen balance, albuminemia, and oxygen consumption; conversely, the CEN experience, evaluated by patients on analogical visual scales, was significantly better endured in the ambulatory group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084334 TI - A reconstruction of the gene for ribulose bisphosphate carboxylase from Rhodospirillum rubrum that expresses the authentic enzyme in Escherichia coli. AB - Escherichia coli plasmid pRR36, which expresses Rhodospirillum rubrum ribulose bisphosphate carboxylase/oxygenase (EC 4.1.1.39) as a fusion protein [Nargang et al., Mol. Gen. Genet. 193 (1984) 220-224], was used to construct a new clone of the carboxylase gene (rbc) whose expression product is the wild-type enzyme. This construction entailed removing all lacZ-coding sequences and a portion of the 5' noncoding leader of the R. rubrum rbc gene. The highest specific activity of carboxylase was observed with an expression vector which juxtaposed the trp-lac (tac) hybrid promoter with the R. rubrum ribosome binding site and the rbc structural gene. The carboxylase expressed in E. coli JM107 was purified to near homogeneity and, based on subunit Mr and specific enzymic activity, the isolated protein appeared indistinguishable from authentic ribulose bisphosphate carboxylase from R. rubrum. N-terminal sequence analyses of the cloned enzyme verified that the cloned and wild-type enzymes are the same. PMID- 3084335 TI - [Metabolic kinetics and biological action of heavy water (D20)]. PMID- 3084336 TI - An evaluation in institution-based respite care. PMID- 3084337 TI - [Basis for the maximum allowable concentration of thiourea in the air of the work zone]. PMID- 3084338 TI - The cost of cost containment. PMID- 3084339 TI - Mucus, pepsin, and peptic ulcer. PMID- 3084340 TI - Mucus degradation by pepsin: comparison of mucolytic activity of human pepsin 1 and pepsin 3: implications in peptic ulceration. AB - The ability to digest mucus, mucolytic activity of isolated pepsins and samples of human gastric juice has been assayed by measuring the fall in viscosity when incubated with purified pig gastric mucus glycoprotein. Pure human pepsin 1, the peptic ulcer associated pepsin, digested gastric mucus glycoprotein at a faster rate than did pure human pepsin 3 (the principal human pepsin), or the equivalent pig pepsin (pepsin A). At pH 2.0 pepsin 1 had twice the mucolytic activity of pepsin 3. Above pH 3.8 this difference became more marked and whereas pepsin 1 caused substantial mucolysis up to and including pH 5.1, pepsin 3 had minimal activity. At pH 4.0 pepsin 1 had six times the mucolytic activity of pepsin 3. Gastric juices from patients with duodenal ulcer each exhibited substantial mucolytic activity between pH 2 to 5, similar to that of pepsin 1. In contrast, gastric juice from non-symptomatic volunteers exhibited little mucolytic activity above pH 4. Analysis of the mucus glycoprotein by gel filtration showed that an increase in lower molecular weight, pepsin degraded, glycoprotein was associated with the fall in mucus viscosity for all enzyme preparations. These results showed that pepsin 1 can digest the mucus more effectively than pepsin 3 and at higher pH values. The raised concentrations of pepsin 1 in the juice of peptic ulcer patients may thus promote the ulcerative process by increased erosion of the mucus barrier under conditions likely to pertain in the duodenal bulb as well as the stomach. PMID- 3084342 TI - Does food affect acute inflammatory bowel disease? The role of parenteral nutrition, elemental and exclusion diets. PMID- 3084341 TI - Haemostatic problems in liver disease. PMID- 3084343 TI - There is more to healing ulcers than suppressing acid. PMID- 3084344 TI - Controlled trial of bowel rest in the treatment of severe acute colitis. AB - In a prospective, randomised clinical trial, 47 patients with severe, acute, non infective colitis treated with 60 mg intravenous prednisolone daily, received either bowel rest with parenteral nutrition or oral diet. Although those who received 'bowel rest' experienced a reduction in daily stool weight, there were no differences in the operation or mortality rates between the groups. Fourteen of the 27 patients with ulcerative colitis, but none of the 16 patients with Crohn's disease required urgent surgery. Bowel rest did not affect the outcome in severe ulcerative colitis treated with intravenous prednisolone. Ulcerative colitis and Crohn's colitis behaved differently in the acute attack. PMID- 3084345 TI - Acid, pepsin, and mucus secretion in patients with gastric and duodenal ulcer before and after colloidal bismuth subcitrate (De-Nol). AB - Basal and pentagastrin stimulated gastric secretion was measured in seven patients with duodenal, and six with gastric ulcers before and after four weeks' treatment with colloidal bismuth subcitrate (as De-Nol), one tablet four times a day. Each duodenal and all but one of the gastric ulcers healed. After De-Nol there were no significant changes in basal, or pentagastrin stimulated volume, acid output, or primary parietal component. There were marked decreases in basal (duodenal ulcer -25%; gastric ulcer -16%) and pentagastrin stimulated total pepsin outputs, (duodenal ulcer -42%, gastric ulcer -36%). There were insignificant decreases in basal output of mucus, but postpentagastrin stimulated mucus output was significantly inhibited (p less than 0.05) in patients with duodenal (-16%) and with gastric ulcer (-27%). The drop in gastric proteolysis after De-Nol is unlikely to be because of the healing of the ulcers and is more likely to be because of the drug. The ulcer healing efficacy of De-Nol may be related to this decline in the proteolytic action of gastric juice, but is unlikely to be because of a quantitative change in mucus, or in acid secretion. PMID- 3084346 TI - Lactose digestion by human jejunal biopsies: the relationship between hydrolysis and absorption. AB - The relationship between lactose hydrolysis and absorption of released glucose was investigated by determining the kinetics of lactose digestion by jejunal biopsies incubated in vitro. Lactase activity in intact biopsies correlated with conventional assay of tissue homogenates (r = 0.85, p less than 0.001), and glucose uptake from 28 mM lactose was directly proportional to lactase activity (r = 0.95, p less than 0.001) in 21 subjects with normal lactase levels, six with hypolactasia (primary or secondary to coeliac disease) and two with lactose intolerance but normal lactase activity. Kinetic analysis at 0.56-56 mM lactose in five normal subjects showed saturable kinetics for hydrolysis (app Km = 33.9 +/- 2.2 mM; app Vmax = 26.5 +/- 1.1 nmol/min/mg dry weight) but glucose uptake could be fitted to a model either of saturable uptake (app Kt = 47.2 +/- 0.3 mM; app Jmax = 14.1 +/- 0.2 nmol/min/mg) or saturable uptake plus a linear component (app Kt = 21.3 +/- 1.15; app Jmax = 4.59 +/- 0.12; app Kd = 0.093 +/- 0.010 nmol/min/mg/mM). The proportion of glucose taken into the tissue did not significantly exceed 50% of the total released at any lactose concentration suggesting the lack of an efficient capture mechanism for the released glucose. The results suggest that lactose hydrolysis is the rate limiting step in the overall absorption of glucose from lactose in vitro, and that the relationship between hydrolysis and absorption is the same in normal subjects and in hypolactasic subjects. PMID- 3084347 TI - Transdermal nitroglycerin ointment and patches. PMID- 3084348 TI - Autologous bone marrow transplantation in haematologic malignancies. PMID- 3084349 TI - Aspartate aminotransferase and pyruvate kinase activities in erythrocytes separated according to age by gradient centrifugation. PMID- 3084350 TI - Iron status and anemia in thalassemic Sardinian carriers. PMID- 3084351 TI - Serum lactate dehydrogenase isoenzyme pattern in acute transformation of chronic granulocytic leukemia. PMID- 3084352 TI - Splenomegalic immunocytoma with circulating hairy cells. Report of eight cases and revision of the literature. PMID- 3084353 TI - Evaluation of a polychemotherapeutic regimen including Idarubicin (4 demethoxydaunorubicin) in relapsed acute lymphocytic leukemia. PMID- 3084354 TI - Thrombotic thrombocytopenic purpura (TTP) treatment: Italian cooperative retrospective study on 29 cases. PMID- 3084355 TI - Double heterozigosity HbE/alpha-thalassemia in a Cambodian child. PMID- 3084356 TI - Hemolysis in Rh-negative female recipient after Rh-incompatible bone marrow transplantation for chronic myeloid leukemia. PMID- 3084357 TI - Immunoblastic lymphoma following therapy for Hodgkin's disease. A case report. PMID- 3084358 TI - Possible usefulness of ticlopidine in combined treatment of thrombotic thrombocytopenic purpura. Report of one case. PMID- 3084359 TI - Pleural involvement in multiple myeloma. PMID- 3084360 TI - Acute leukemia occurring in a primary neoplasia (secondary leukemia). A Review of biological, epidemiological and clinical aspects. PMID- 3084361 TI - High resolution chromosomes for marrow transplant monitoring. PMID- 3084362 TI - More on low-dose Ara-C. PMID- 3084363 TI - Prognostic value of the staging system proposed by Tura for chronic myeloid leukemia. PMID- 3084364 TI - Endothelial stimulation by DDAVP in von Willebrand's disease and haemophilia. AB - Desamino-D-arginine vasopressin (DDAVP) is known to stimulate factor VIII (FVIII) and plasminogen activator release from endothelial cells, and has been shown to stimulate prostacyclin (PGI2) production in normal and haemophilic subjects. In von Willebrand's disease (vWd) some patients have a dissociate response with regard to FVIII and plasminogen activator. The aim of our study was to compare the PGI2, FVIII and plasminogen activator response to DDAVP infusion in vWd with the response to DDAVP in normal and haemophilic subjects. PGI2 metabolites thromboxane B2 (TxB2), factor VIII coagulant activity, factor VIII-related antigen and plasminogen activator were measured before and after DDAVP infusion. There was a significant increase in PGI2 metabolites, factor VIII-related antigen and plasminogen activator in all groups following DDAVP, but no effect on TxB2 was found, and there was no evidence of any dissociate response to DDAVP in any of the groups. Basal levels of PGI2 metabolites, however, were significantly lower in vWd as compared to normal and haemophilic subjects. Post-DDAVP levels of PGI2 metabolites were also significantly lower in vWd as compared with normal subjects. This may be due to a reduced stimulus to PGI2 production in vWd secondary to defective platelet adhesion. PMID- 3084365 TI - Mouse (Mus musculus) as intermediate host of Sarcocystis sp. from the goshawk (Accipiter gentilis). AB - Sporocysts from the goshawk (Accipiter gentilis) were experimentally transferred to the mouse (Mus musculus). It was found that the goshawk is the host of one of the sarcosporidians inducing muscle sarcocystosis in mice. Thin-walled, sporulated oocysts expelled by the goshawk measured 16.5-19.0 X 12.0-13.0 micron. Those which measured 12.0-13.5 X 8.2-9.0 micron were widely elliptical, with rounded poles. No asexual reproduction of parasites was detected in the viscera of mice. The cysts started to appear in skeletal muscles on day 20 after oral infection with 10,000 or 100,000 sporocysts per mouse. The cysts measuring 15-630 X 18-65 micron contained widely oval metrocytes (2.8-4.3 X 1.5-2.8 micron) or banana-shaped cystozoites (6.0-8.0 X 2.0-3.8 micron). Three months after infection the cysts were found also in the tongue of mice. No morphological differences were observed between the oocysts-sporocysts from owls (Tyto alba and Asio otus) and goshawk, not even between the muscle cysts of these sarcosporidians in mice. The possibility of passaging the species Sarcocystis dispersa from the long-eared owl through the digestive tract of goshawk is discussed. PMID- 3084366 TI - [Therapeutic effectiveness and safety of dihydroergocristine. A study of 9,702 patients]. PMID- 3084367 TI - [The analysis of immunoregulation of idiotype synthesis by monoclonal anti idiotypic antibody]. AB - Idiotype (Id) is the epitope in the variable region of immunoglobulin and each immunoglobulin has its own Id. Jerne, in his "Network theory", explained that interaction between Id and anti-Id antibody might regulate cellular and humoral immune response. Many experimental results suggest that anti-Id antibody plays important role on immunoregulations but the mechanism is not known in detail. In the present study, the monoclonal anti-Id antibody (TN 16, IgG1) against M protein (IgG . k) from a patient (TN) with multiple myeloma was prepared with hybridoma technique and the Id positive mononuclear cells (MNCs) in TN peripheral blood were studied by indirect immunofluorescent method. The effect of anti-Id antibody on Id production by TN MNCs was also examined. TN 16 did not react with Cohn Fr. II IgG (pooled normal human IgG) at various concentrations and specifically reacted with TN IgG by radioimmunoassay. The binding between TN 16 and 125I labelled TN IgG was not inhibited by Cohn Fr. II IgG, F(ab')2 fragment of Cohn Fr. II IgG or other IgG k myeloma sera, but only TN IgG and F(ab')2 fragment of TN IgG i.e. idiotype. TN MNCs were stained with TN 16 followed by FITC conjugated anti-mouse IgG. From 9.7 to 18.2% of Id positive cells were detected. The effect of TN 16 on the production of idiotypic IgG was also studied. TN MNCs were cultured with or without TN 16 for 48 hrs and washed to remove TN 16. These cells were resuspended to a concentration of 1 x 10(6)/ml and cultured for 5 days. The production of total IgG was not affected by treatment with TN 16. On the other hand, the production of idiotypic IgG treated with TN 16 decreased from 87.3% ng/ml to 35.0 ng/ml. These results indicate that the mononuclear cells bearing the same idiotype as that of M protein on their surfaces are increased in peripheral blood in this case and that anti-Id antibody suppresses the production of idiotypic immunoglobulin selectivelly. PMID- 3084368 TI - [Enterotoxin-like factor(s) produced by Vibrio parahaemolyticus]. AB - Culture filtrates obtained from several isolates of Vibrio parahaemolyticus were tested for their enterotoxin-like activities. Also their antigenic relationship with cholera enterotoxin and Kanagawa hemolysin were tested. In the Chinese Hamster Ovary (CHO) cells assay which are usually employed for detecting cholera toxin or heat labile enterotoxin produced by enterotoxigenic Escherichia coli, crude culture filtrates obtained from both Kanagawa positive and negative strains isolated from patients showed positive reaction whereas most of the Kanagawa negative strains isolated from environmental sources did not. After concentration, however, both the culture filtrates of Kanagawa positive and negative strains of Vibrio parahaemolyticus showed positive reactions in CHO cell assay and rabbit skin permeability assay but not in rabbit ileal loop test. Antisera against concentrated culture filtrates obtained from both Kanagawa positive and negative strains neutralized neutralized the activities of concentrated culture filtrates in CHO cell assay and Rabbit permeability assay but not of cholera toxin and Kanagawa hemolysin. Immunodiffusion test was also carried out using the antisera and the concentrated culture filtrates obtained from both of Kanagawa positive and negative strains of Vibrio parahaemolyticus. The antisera cross-reacted with all concentrated culture filtrates obtained from both Kanagawa positive and negative strains but not reacted with cholera toxin and Kanagawa hemolysin. These results indicated that both of Kanagawa positive and negative strains of Vibrio parahaemolyticus can produce the enterotoxin-like factor(s) such as cholera enterotoxin or heat labile enterotoxin produced by enterotoxigenic Escherichia coli, but this factor(s) dose not show cross antigenicity with cholera enterotoxin and the Kanagawa hemolysin produced by Kanagawa positive Vibrio parahaemolyticus. PMID- 3084369 TI - Extracts of protozoa contain materials that react specifically in the immunoassay for guinea pig insulin. AB - Extracts of protozoa contain materials that resemble guinea pig insulin, which is noted for its unusual structure and properties. The protozoan derived materials react in the radioimmunoassay for guinea pig insulin; some but not all of these immunoreactive materials migrate on gel filtration in the position of authentic guinea pig insulin. Experiments were done to exclude artifacts in the assay as well as inadvertent contamination by guinea pig insulin. By immunological methods, we segregated the guinea pig type immunoactivity from that which has rat/pork type immunoactivity. These findings extend our studies of extracts of guinea pig tissues which also have these two types of insulin immunoactivities. PMID- 3084370 TI - The pleiotypic response to serine in erythroblastic leukemic cells. AB - Erythroblastic leukemic (EBL) cells incubated in media containing essential amino acids, glutamine and serine incorporate more [3H]-leucine into protein than those incubated without serine. Cells incubated with serine contain higher intracellular serine concentrations and display increased rates of peptide chain initiation on polyribosomal profile analysis. Deficiency of serine inhibited protein synthesis more than deficiencies of most other single essential amino acids, but no further inhibition was seen when single essential amino acids were removed from serine deficient media. Serine also enhanced the uptake of [3H] uridine and its transfer to RNA while several essential amino acids had no effect. We conclude that in EBL cells, serine is an essential amino acid and that exogenous repletion of intracellular concentrations induces a positive pleiotypic response. We have previously shown that after incubation with serine for 15 min. EBL cells have greater numbers of plasmalemma insulin receptors. Regulation of cell surface receptors may therefore comprise another limb of the pleiotypic response. PMID- 3084371 TI - Single dose responses to the gonadotropin-releasing hormone agonist analogue [(imBz 1)-D-His6,Pro9-NEt]GnRH. AB - The agonist analogue of gonadotropin-releasing hormone (GnRH), [(imBz1)-D His6,Pro9-NEt]GnRH, has a potency 200 times that of the native hormone in vitro. In single dose studies in man, this analogue resulted in 2- to 4-fold elevation of LH and FSH, and demonstrated a prolonged duration of activity. [(imBz1)-D His6,Pro9-NEt]GnRH appears to be safe and, as with other analogues of GnRH, may have application to clinical medicine. PMID- 3084372 TI - Hormonal regulation of testicular human chorionic gonadotropin binding and steroidogenesis in adult mice with different forms of hereditary diabetes and obesity. AB - The regulation of testicular hCG binding and steroidogenesis in adult mutant mice with hereditary diabetes and obesity was studied. Low doses of hCG caused no change in hCG binding in obese (ob/ob) mice, whereas, in diabetic (db/db) mice, the increase in binding measured 24 h after hCG administration was not as great as in normal males. Intermediate doses of hCG caused a decrease in hCG binding in obese and normal mice, but not in diabetic animals. However, 72 h after injection of intermediate doses of hCG, a decrease in hCG binding also was observed in diabetic mice. Plasma testosterone was elevated 24 h after hCG injection in all types of mice studied, but the increase in diabetic mice was smaller than in normal animals. However, 72 h after treatment with hCG, plasma testosterone was still elevated in diabetic mice, but not in normal males. In vitro, hCG stimulated testicular testosterone synthesis in all groups of mice, but the observed increase was smaller in diabetic and obese than in normal animals. Plasma LH levels were higher in diabetic than in normal mice, whereas plasma FSH and prolactin levels were lower in obese mice than in normal animals. All parameters (i.e., LH receptors and circulating hormone levels) measured in yellow (Ay/a) mice were similar to those in normal (a/a) mice. The present study indicates that in these models for noninsulin-dependent diabetes, the testicular metabolism of LH receptors and capacity to secrete steroids is altered. PMID- 3084373 TI - Gonadotrophin suppression by the synthetic androgen mesterolone in idiopathic oligospermia. PMID- 3084375 TI - Have courts taken legal risk from feeding refusals? PMID- 3084376 TI - Philly spawns 'son of DRGs'. PMID- 3084374 TI - An innovative approach to assessing outcome of long-term psychiatric hospitalization. AB - The failure of research on long-term hospital treatment to show consistent relationships between length of stay and treatment outcome may reflect a need for more refined measures to evaluate long-term treatment. The authors developed an individualized method of assessing improvement in patients' major areas of impairment over the course of treatment. Using the new approach and two more traditional methods, the authors evaluated the outcome of 37 discharged long-term patients of a private psychiatric hospital who had been rated at admission and discharge on 21 variables related to ego function; affective symptoms; risk of suicide, self-destructiveness, and violence; substance abuse; level of treatment alliance; and, at discharge only, on overall level of improvement. Although the traditional methods failed to show a correlation between length of stay and most of the variables, the individualized approach found that a longer hospital stay was related to greater improvement in areas of most impaired functioning. PMID- 3084377 TI - Autopsy data and DRG reimbursement. PMID- 3084378 TI - Idiotypic games within the immune network. AB - In this paper, we have considered the problem of selection of available repertoires. With Ab2 as immunogens, we have used the idiotypic cascade to explore potential repertoires. Our results suggest that potential idiotypic repertoires are more or less the same within a species or between different species. A given idiotype "a la Oudin" can become a recurrent one within the same outbred species or within different species. Similarly, an intrastrain crossreactive idiotype can be induced in other strains, even though there is a genetic disparity between these strains. The structural basis of this phenomenon has been explored. We next examined results showing the loss and gain of recurrent idiotypes without any intentional idiotypic manipulation. A recurrent idiotype can be lost in a syngeneic transfer and a private one can become recurrent by changing the genetic background. The change of available idiotypic repertoires at the B cell level has profound influences on the idiotypic repertoires of suppressor T cells. All these results imply that idiotypic games are played by the immune system itself, a strong suggestion that the immune system is a functional idiotypic network. PMID- 3084379 TI - [Induced pemphigus and genetic predisposition. Apropos of 3 clinical cases]. PMID- 3084380 TI - The organization of immunoglobulin variable kappa chain genes on mouse chromosome 6. AB - One mouse with a known recombination (NAK) at the Igk locus on chromosome 6 and two new recombinants [B6.PL (75NS) and B6.PL (85NS)] were examined using a series of probes, each of which is specific for a set of immunoglobulin (Ig) Vk genes. Under high stringency conditions, each probe detects from 1 to 19 Bam HI restriction endonuclease fragments (REFs) in genomic DNA by Southern transfer hybridization techniques. Analysis of the REF patterns indicate that the NAK recombination event occurred within the variable region of Igk. The REF patterns of the two B6.PL congenic mice provided two additional recombination events which could be examined. Although some of the REFs had shared mobility among the parental strains, at least 1 and up to 13 polymorphic REFs were present for a given probe among the NZB and AKR parental strains. The results from the NAK mouse indicate that at least some members of Vk4, Vk8, Vk10, and Vk21 were on one side of the recombination event linked to the Lyt-2 alpha and Igk-Ef1 alpha alleles of AKR, while the Vk9, Vk11, and Vk24 REF patterns came from the NZB parental strain linked to the Igk-Ef2 beta (Vk1) allele. The two B6.PL congenics produced a refined map on the Lyt-2, Lyt-3 side of the Vk region. The B6.PL (85NS) mice retained the Vk21 REF pattern of the Lyt-2 alpha, Lyt-3 alpha donor strain PL/J, while displaying the C57BL/6 REF pattern for the other Vk gene groups tested. The B6.PL (75NS) mice retained the REF patterns of PL/J for Vk21 and Ef-1, indicating a third recombination. This indicates the Vk gene order is (Lyt-2; Vk21); Ef-1; (Vk4; Vk8; Vk10); and (Vk9; Vk11; Vk24; Ef-2). PMID- 3084381 TI - Development of antibodies to protective antigen and lethal factor components of anthrax toxin in humans and guinea pigs and their relevance to protective immunity. AB - A competitive inhibition enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies in serum to the protective antigen (PA) and lethal factor (LF) components of anthrax toxin. Current human vaccination schedules with an acellular vaccine induce predictable and lasting antibody titers to PA and, when present in the vaccine, to LF. Live spore vaccine administered to guinea pigs in a single dose conferred significantly better protection than the human vaccines (P less than 0.001), although they elicited significantly lower (P less than 0.0005) anti-PA and anti-LF titers at time of challenge with virulent Bacillus anthracis. Substantial anti-PA and anti-LF titers may not, therefore, indicate solid protective immunity against anthrax infection. The ELISA system was also shown to be capable of detecting anti-PA and anti-LF antibodies in the sera of individuals with histories of clinical anthrax. The advantage of ELISA over the Ouchterlony gel diffusion test and indirect microhemagglutination assay are demonstrated. There was a highly significant degree of correlation between ELISA and the indirect microhemagglutination assay (P less than 0.0005); but ELISA was markedly superior in terms of reproducibility, reliability, specificity, and simplicity in performance and stability of the bound antigen. PMID- 3084382 TI - Isolation and characterization of protective T cells induced by Listeria monocytogenes. AB - Rats convalescing from a recent infection with Listeria monocytogenes generate T cells which can protect recipient rats against a challenge infection with that organism. Using monoclonal antibodies that react with some but not all rat peripheral T cells, the T-cell mediators of acquired resistance to infection (TCRI) were isolated by panning and characterized by using a fluorescence activated cell sorter. Many L. monocytogenes-immune TCRI were relatively large cells as judged by their light-scattering properties. That finding accords with previously reported cytokinetic data and velocity sedimentation analyses which revealed that the majority of L. monocytogenes-immune TCRI are lymphoblasts. In the current investigation, the surface antigenic profile of these mediator T cells was revealed as W3/25+ OX8+ OX4+ RT6.1-. That phenotype is identical to that of L. monocytogenes-induced prekiller cells which are formed as part of the animal's cell-mediated response to infection. Like prekiller cells and their differentiated counterparts, L. monocytogenes-immune TCRI adhere preferentially to monolayers of syngeneic fibroblasts. The results indicate that L. monocytogenes-immune TCRI belong to a minor subset of peripheral T cells which also contains T cells that have the cytotoxic potential by which L. monocytogenes induced prekiller cells have been defined. PMID- 3084383 TI - Immunization studies with attenuated strains of Bacillus anthracis. AB - Live, attenuated strains of Bacillus anthracis lacking either the capsule plasmid pXO2, the toxin plasmid pXO1, or both were tested for their efficacy as vaccines against intravenous challenge with anthrax toxin in Fischer 344 rats and against aerosol or intramuscular challenge with virulent anthrax spores in Hartley guinea pigs. Animals immunized with toxigenic, nonencapsulated (pXO1+, pXO2-) strains survived toxin and spore challenge and demonstrated postimmunization antibody titers to the three components of anthrax toxin (protective antigen, lethal factor, and edema factor). Immunization with two nontoxigenic, encapsulated (pXO1 , pXO2+), Pasteur vaccine strains neither provided protection nor elicited titers to any of the toxin components. Therefore, to immunize successfully against anthrax toxin or spore challenge, attenuated, live strains of B. anthracis must produce the toxin components specified by the pXO1 plasmid. PMID- 3084384 TI - Opsonization of Listeria monocytogenes type 4b by human adult and newborn sera. AB - We studied the requirements for opsonization of Listeria monocytogenes type 4b with chemiluminescence and bactericidal assays and electron microscopy. Preopsonization with 3% adult serum had good opsonic activity (27,300 +/- 11,000 [standard deviation] counts, chemiluminescence assay), while 3% newborn cord serum was not opsonically active (820 +/- 530 counts, P less than 0.001 versus adult serum). In addition, organisms opsonized with cord serum were not killed (0% bacterial killing) and were less frequently visualized intracellularly on electron micrographs (0 to 4 bacteria per cell) than organisms opsonized with adult serum (70% killing and 10 to 20 bacteria per cell). Opsonic requirements for L. monocytogenes type 4b at low concentrations of serum were studied in detail with Sepharose-protein A-treated adult serum to obtain immunoglobulin G (IgG) and IgM fractions and zymosan-absorbed and C4 inactivator-treated serum to obtain alternative and classical complement pathway-deficient sera, respectively. In the presence of complement, IgM was opsonically active (59% of control) while IgG was not (6% of control). In addition, classical complement activity was required for efficient opsonization (greater than 100% of control) while the alternative complement pathway was unnecessary (3% of control). Since IgM is absent and classical complement activity is low in neonatal serum and at the common sites of neonatal Listeria infection, the requirement for IgM and classical complement activity for efficient opsonization of L. monocytogenes type 4b at low serum concentrations may be a factor in the pathogenesis of neonatal disease. PMID- 3084385 TI - Comparative efficacy of Bacillus anthracis live spore vaccine and protective antigen vaccine against anthrax in the guinea pig. AB - Several strains of Bacillus anthracis have been reported previously to cause fatal infection in immunized guinea pigs. In this study, guinea pigs were immunized with either a protective antigen vaccine or a live Sterne strain spore vaccine, then challenged with virulent B. anthracis strains isolated from various host species from the United States and foreign sources. Confirmation of previously reported studies (which used only protective antigen vaccines) was made with the identification of 9 of the 27 challenge isolates as being vaccine resistant. However, guinea pigs immunized with the live Sterne strain spore vaccine were fully protected against these nine isolates. In experiments designed to determine the basis of vaccine resistance, guinea pigs which were immunized with individual toxin components and which demonstrated enzyme-linked immunosorbent assay antibody titers comparable to those induced by Sterne strain vaccine were not protected when challenged with a vaccine-resistant isolate. We concluded that antibodies to toxin components may not be sufficient to provide protection against all strains of B. anthracis and that other antigens may play a role in active immunity. As a practical matter, it follows that the efficacy of anthrax vaccines must be tested by using vaccine-resistant isolates if protection against all possible challenge strains is to be assured. PMID- 3084386 TI - Arthropathic properties of gonococcal peptidoglycan fragments: implications for the pathogenesis of disseminated gonococcal disease. AB - We examined the arthropathic activity of purified peptidoglycan (PG) fragments derived from (i) lysozyme-resistant, extensively O-acetylated PG from Neisseria gonorrhoeae FA19 (O-PG), and (ii) lysozyme-sensitive, O-acetyl-deficient PG from N. gonorrhoeae RD5 (non-O-PG). Male Lewis rats were injected intradermally in the tail with 200 micrograms of PG emulsified in mineral oil and water (1:1) or with the oil and water emulsion alone (controls). Quantitation of hind paw size indicated that macromolecular PG of various chemical and physical forms induced paw swelling (P versus controls, less than 0.01) that was evident at about day 14 and that reached a maximum at about day 24. PG-mediated paw swelling was accompanied by intense synovitis with some cartilage and bone involvement. The minimal arthropathic dose of soluble macromolecular PG was 20 micrograms per rat. Of particular interest was that macromolecular O-PGs from strain FA19 caused considerably more extensive swelling than did either their RD5 non-O-PG counterparts or the homologous FA19 PG that had been de-O-acetylated by mild alkali treatment. This suggested that the persistence of hydrolase-resistant high molecular-weight fragments, afforded by extensive O-acetylation, may be important for optimal expression of arthropathic activity. However, oligomeric PG was not an absolute requirement, since even low-molecular-weight fragments, including the anhydro-muramyl-containing disaccharide peptide monomer released by growing gonococci, were also arthritogenic. Experiments employing purified gonococcal lipopolysaccharide indicated that the arthropathic activity of PG preparations was not due to contaminating lipopolysaccharide. Based on the arthritogenicity of gonococcal PG in this model system, we suggest that PG may play a role in the pathogenesis of gonococcal arthritis, and that such an activity might be potentiated by the persistence of hydrolase-resistant O-PG. PMID- 3084387 TI - Effects of acetate and bicarbonate dialysis on cardiac performance, transmural myocardial perfusion and acid-base balance. AB - The effects of acetate and bicarbonate dialysis on cardiac performance, myocardial oxygen balance and acid-base balance were evaluated in 7 patients with end-stage renal failure. During acetate dialysis cardiac output increased and was significantly higher than during bicarbonate dialysis (p less than 0.05). Systemic vascular resistance was significantly lower during acetate than during bicarbonate dialysis (p less than 0.05). The myocardial oxygen balance estimated from the supply/demand ratio (DPTI/SPTI) was significantly reduced after acetate dialysis and significantly lower than during bicarbonate dialysis (p less than 0.05). After 90 min acetate dialysis DPTI/SPTI dropped to its lowest value as a result of an excess of myocardial oxygen demand (SPTI) over myocardial oxygen supply (DPTI), signifying transient hypoperfusion of the subendocardium which did not occur during bicarbonate dialysis. Acidosis was more adequately corrected with bicarbonate dialysis, and there was no change in pCO2 which was significantly higher than during acetate dialysis (p less than 0.05). During bicarbonate dialysis a stable hemodynamic circulation and well balanced acid-base values were seen. Acetate dialysis leads to improvement in left ventricular performance, but at the expense of myocardial oxygen balance, which falls to marginal safety levels in uremic patients. PMID- 3084388 TI - Sterilization of therapeutic immunoadsorbents by ionizing radiation. AB - The application of ionizing radiation (gamma-rays from 60Co) to sterilize therapeutic immunoadsorbents (IA)s was investigated. The IAs were porous bead carriers immobilizing anti-IgE antibodies and were irradiated in both the freeze dried and precipitated (wet) states. The IgE removal (%), the IgE adsorption capacity of IA, was acceptable in terms of practical use even after an irradiation dose of 2.5 Mrad in the precipitated state; the anti-IgE antibody itself lost much of its activity, possibly because of intermolecular crosslinking of antibody molecules, after being irradiated with a dose at least of 0.5 Mrad. In the freeze-dried state only IA consisting of CPG-1400 could tolerate a dose of 2.5 Mrad. Dose-survival curves were obtained using Bacillus pumilus spores in both the freeze-dried and precipitated IAs and the D-values were calculated to be respectively 0.27 and 0.31 Mrad. Thus, ionizing radiation may be applicable for sterilizing IAs in the precipitated state and in the freeze-dried state for an IA consisting of CPG-1400 although the initial bioburden on IA should be low. PMID- 3084389 TI - Comparative study of acetazolamide and spironolactone on body fluid compartments on induction to high altitude. PMID- 3084390 TI - Effects of tumor promoters on growth and on cellular redistribution of phospholipid/Ca2+-dependent protein kinase in human breast cancer cells. AB - Active, structurally unrelated tumor promoters (12-0-tetradecanoyl-phorbol-13 acetate (TPA), teleocidin and aplysiatoxin) inhibit growth of mammary carcinoma cells (MCF7- greater than BT-20 greater than MDA-MB-231 greater than = ZR-75-1 greater than HBL-100). This efficiency in inhibiting cell growth correlates with the tumor-promoting activity of a series of phorbol ester derivatives. The phospholipid/calcium-dependent protein kinase (PKC), a target for phorbol ester action, was measured by polyacrylamide gel electrophoresis. The levels of PKC were higher (p less than 0.001) in estrogen-receptor-negative than in estrogen receptor-positive cells. Treatment of cells with active tumor promoters results in time- and dose-dependent translocation of cytosolic PKC to membrane fractions. Less potent phorbol esters induce only partial translocation of PKC (i.e., decrease of cytosolic without increase in membrane-bound PKC), whereas inactive esters have no effect. No correlation was found between PKC concentration or the amount of PKC translocated to membranes and the sensitivity of the respective cells to TPA. It is concluded that tumor-promoter-mediated growth inhibition of breast cancer cell lines is due to mechanism(s) occurring after the translocation of PKC. PMID- 3084391 TI - Characterization of a tumorigenic murine T-lymphoid-cell line spontaneously derived from an IL-2-dependent T-cell line. AB - The establishment of IL-2-independent T-cell lines spontaneously derived from long-term IL-2-dependent cytotoxic T-cell lines is described. Two lines (cloned and uncloned) studied in detail have shown the following characteristics: (1) Permanent loss of IL-2 dependence. (2) Partial or complete loss of both cytotoxic activity and the IL-2 receptor. (3) Increased expression of T-cell membrane markers (Thy1.2, Lyt1.2) compared with the parental line. (4) Lower level of DNA methylation than in freshly obtained lymphoid cells. (5) Different karyotypic pattern from the parental IL-2-dependent line, with a mean number of 39-40 chromosomes and a resemblance to T leukemic lines. (6) Leukemia caused in normal syngeneic C57BL/6 mice by the uncloned line, in contrast to the cloned IL-2 independent line or the parental dependent line. Unlike established leukemic lines, however, the independent line gave rise to tumors which regressed in some mice within a few days of their appearance. These findings suggest that T-cell lines maintained with IL-2 for prolonged periods of time (greater than 3 months) can undergo transformation and, therefore, should not be utilized for immunotherapeutic purposes. PMID- 3084392 TI - Depth cerebral electrical activity in man during hypnosis: a brief communication. PMID- 3084393 TI - The effects of a comprehensive self-hypnosis training program on the use of factor VIII in severe hemophilia. PMID- 3084394 TI - Antiepileptic effects of globulin-N, an intact human immunoglobulin and its tissue-distribution in kindled cats. AB - The antiepileptic effects of globulin-N, an intact human immunoglobulin was examined, using the amygdaloid kindled animals prepared by the method of Goddard et al. [1969] and Wada et al. [1974 b]. In the non-treated kindled cats, kindled convulsion and after-discharge (AD) were simultaneously created at 24-hour intervals by electrically stimulating generalized seizure-triggering threshold (GST) in amygdala, hippocampus and neocortex. The kindled cats, treated intravenously with 200 mg/kg of globulin-N, the generalized convulsion and AD produced by GST-stimulation disappeared entirely from 30 min to 8 days in 8 out of 10 cases. Furthermore, kindled cats treated with phenobarbital and phenytoin showed inhibition of GC and AD by GST-stimulation for 24-48 hours. Globulin-N was determined to have a plasma half-life of about 10 days in the kindled cats, and was presented immunohistochemically in the visceral organ, brain and spinal cord. The administered globulin-N passed through the BBB easily in the kindled cats with GST stimulation induced epileptic seizures, and was apparently taken up by the nerve and glial cells in the cerebral cortex and other deep structures of the central nervous system. These results may not only yield clues for the elucidation of the antiepileptic mechanisms of globulin-N, but may also support the clinical use of globulin-N in patients with intractable epilepsy [Ariizumi et al. 1982], including epileptic psychosis. PMID- 3084395 TI - The aging enterprise: in whose interests? AB - This paper revisits the aging enterprise in the context of the new competitive business ideology. Public policy has created an aging enterprise that assures that the needs of the aged will be processed and treated as a commodity. The medical-industrial complex, which comprises the most significant part of the aging enterprise, is a primary beneficiary of the recent reformulation of values and expectations vis-a-vis the state and the private sector. The new business ideology in health is aimed not only at controlling costs but, more importantly, at establishing health care as a market good like any other. Issues of access to needed services are raised for Medicare and Medicaid beneficiaries and for the uninsured. Budget cuts, medical cost control, and the market ideology are resulting in greater fragmentation, privatization, and corporatization of services, as indicated by the author's research on the private nonprofit health and social services sector in a sample of 8 states and 32 communities. In this paper, age-segregated politics and policies in the United States are challenged to utilize grass-roots political efforts that cross age and class barriers. Single-interest aging-based policies are criticized as a form of selfish separatism that could supplant an important and vitally needed intergenerational and coalition strategy. PMID- 3084396 TI - Treacher-Collins syndrome and neurofibromatosis. PMID- 3084397 TI - Comparison of conformational properties of proline and threonine residues. AB - The conformational role of Thr was investigated by 13C-n.m.r. and CD methods using a following series of tetrapeptides: Thr-Ala-Ala-Ala, Ala-Thr-Ala-Ala, Ala Ala-Thr-Ala and Ala-Ala-Ala-Thr. It was found that introduction of Thr in every position of the tetraalanine peptide chain distinctly influences conformational equilibria of the peptides. An increase of beta-turn forms in conformational equilibria is induced by ionization of the terminal carboxyl group, independent of threonine position in the peptide chain. Threonine in position 1 or 3 of the peptide chain seems to have some importance for beta-turn formation in acid solution. PMID- 3084398 TI - Use of microbore high-performance liquid chromatography for purifying subnanomole levels of polypeptides for microsequencing. Structural studies on the murine plasma cell antigen PC-1. AB - A procedure for the purification of subnanomole levels of polypeptides has been developed. Reversed-phase high performance liquid chromatography on short (10 cm or less) microbore (1-2 mm internal diameter) columns has been used to fractionate and purify a number of tryptic peptides generated from approximately 600 pmol of purified murine plasma cell antigen PC-1, a major membrane glycoprotein on all cells secreting immunoglobulins. The use of reversed-phase microbore columns permits the recovery of subnanomole amounts of polypeptides from large volumes in high yield (greater than 90%) and in small eluent volumes (40-60 microL) which can be loaded directly onto the gas-phase sequencer without further concentration. This procedure avoids the severe sample loss which frequently occurs with other concentration procedures such as lyophilization and evaporation. The use of a photodiode-array detector for identifying tryptophan containing peptides from on-the-fly, ultraviolet spectra is described. This procedure permits the selection of tryptophan-containing peptides from complex tryptic digests for use as candidate peptides for oligonucleotide probe construction. Automated Edman degradation was performed on seven tryptic peptides, yielding 110 unique assignments; this corresponds to approximately 11% of the molecule. PMID- 3084399 TI - Chemical and biological characterization of the galactose binding lectins from Trichosanthes kirilowii root tubers. AB - Three galactose binding isolectins have been isolated from Trichosanthes kirilowii root tubers. Two of the isolectins, TK-I and TK-II, are similar in many aspects including molecular weight, amino acid composition, NH2-terminal amino acid residue, blood group and carbohydrate specificities, immunodiffusion and immunoelectrophoretic behavior, hemagglutinating and insulinomimetic activities, and in possessing subunits with different molecular weights. Compared to TK-I and TK-II, lectin TK-III has a larger molecular weight, subunits with the same molecular weight, a single and distinctive NH2-terminal amino acid residue, a different isoelectric point and lower hemagglutinating activity. The three lectins share common antigenic determinants in their structures. beta-Linked terminal oligosaccharides containing D-galactose inhibit hemagglutination induced by the lectins with a higher potency than alpha-linked oligosaccharides. The lectins are non-mitogenic and did not inhibit the concanavalin-A induced mitogenic response of lymphocytes. PMID- 3084400 TI - Elizabeth Bouvia: whose space is this anyway? PMID- 3084401 TI - Aspiration pneumonia in patients fed through nasoenteral tubes. PMID- 3084402 TI - The ecological genetics of introduced populations of the giant toad, Bufo marinus. IV. Gene flow estimated from admixture in Australian populations. AB - Allele frequency variation is described at nine polymorphic enzyme loci in 21 samples from populations of the introduced Giant Toad, Bufo marinus, in the region of Townsville in north Queensland, Australia. Some of these populations appear to have been established through the introgression of other populations that previously had been isolated. Comparisons of allele frequencies at three polymorphic loci between the introgressed populations and the original populations are used to obtain admixture estimates. These are used to estimate a rate of gene flow among the populations of approximately 2 km/year. This is consistent with an estimate based on the rate at which Bufo marinus has colonised new areas in Australia when discontinuities in the pattern of this colonisation are taken into account. The estimate of gene flow is combined with published data on population density to estimate neighbourhood size. The estimate obtained is substantially greater than the effective population size estimate determined previously from data on allele frequency variances in other populations. This discrepancy is most likely due to inaccuracies in the population density estimates, to underestimates of the extent of offspring number variance and perhaps to occasional departures from sex ratio parity. It has important implications for the study of the genetic structure of populations which are discussed. PMID- 3084403 TI - Psychocardiologic perspectives of coronary artery disease. PMID- 3084404 TI - School nutrition programmes--do they fulfil their purpose? AB - School meals in the USA have been in operation for half a century, yet no associated benefits have been claimed, apart from a slight increase in weight-for age. In the UK, Netherlands and other European countries, associated benefits have been slight or scarcely apparent. In developing populations, school meals, although little practised, appear less beneficial than expected. In western populations evaluations have been entirely incommensurate with extent and cost of the practice, for, largely, only assessments of dietary intake and anthropometric parameters have been studied. There has been insufficient enquiry into which intakes of nutrients, and which percentiles of growth standards, relate most meaningfully to scholastic prowess, biochemical and clinical parameters in youth, and health experience in later years. Since school meals, a highly emotional subject, are strongly bound up with national agriculture, and clearly are unlikely to discontinue, the authors consider that attempted modifications should be in line with current recommendations of authoritative dietary bodies, i.e. to encourage reduction in fat intake and an increased intake of fibre-containing foods. PMID- 3084405 TI - The predictive value of skin telangiectasia for late radiation effects in different normal tissues. AB - Alterations in the microcirculation and parenchymal cell loss are common phenomena after irradiation of different organs. Whether parenchymal cell loss is a process well dissociated from vasculoconnective damage, or a consequence of this, is much debated. However, comprehensive radiopathological studies have shown that vasculoconnective tissue is an important common target for late effects in various organs. Scoring of skin telangiectasia was used by us as a clinical assay of late tissue effects after different dose schedules. All studies were done prospectively with standardized skin area, field size and radiation quality. The patients were scored regularly up to 10 years. The number of patients at risk for a prescribed score versus time was calculated with the life table method. The late effects after 5 X 2.0 Gy/wk, in the dose range 40 to 70 Gy and after 2 X 4.0 Gy/wk, in the dose range 40 to 56 Gy have been established. The skin dose is 90% of the referred dose. Dose-response curves, relating the proportion of patients with a certain score at a fixed time and radiation dose and dose-latency curves, relating the latent period for a fixed proportion of patients with a certain score and radiation dose, were constructed. The analysis shows that: ED10/5 yr and ED50/5 yr for 5 X 2.0 Gy/wk is 50 Gy and 65 Gy, respectively, for distinct telangiectasia; The latent period, concerning both a certain frequency and degree of reaction, varies exponentially with dose level; The latent period for 50% of the patients, to obtain a certain score, LP50, is correlated to that for 10%, LP10, with LP50/LP10 = 2.2 +/- 0.2 (S.D.). This correlation is independent of score, total dose, and fractionation; Isoeffective doses for 5 X 2.0 Gy/wk and 2 X 4.0 Gy/wk, determined from the dose-response curves, resulted in the repair exp N between 0.31 and 0.32 and alpha/beta ratio between 2.9 and 3.1 Gy and determined from the dose-latency curves in exp N between 0.30 and 0.32 and alpha/beta ratio between 3.4 and 2.9 Gy. In conclusion, frequent and careful follow-up with registration of normal tissue reactions, until at least 10% of the patients have obtained the prescribed effect, is predictive for the further progression of the late effects. The fractionation characteristics for telangiectasia agree well with those for animal experimental morphological and functional endpoints for late effects in different organs and support the relevance of telangiectasia as a model for predicting late effects. PMID- 3084406 TI - Prevalence, transmission, and pathogenicity of Sarcocystis gigantea of sheep. AB - Between March and May 1983, tongues and esophagi of 355 adult ewes from Colorado and Idaho were examined for grossly visible sarcocysts. Sarcocysts of Sarcocystis gigantea were found in 35 sheep. Cats fed sarcocysts from these naturally infected sheep shed sporocysts in their feces. Two adult ewes and 12 lambs inoculated with 1,000 to 1,000,000 sporocysts were euthanatized at postinoculation days (PID) 146, 230, 265, 391, 721, and 882, and their tissues were fed to Sarcocystis-free cats. All inoculated sheep remained clinically normal except for mild pyrexia between PID 12 and 18. Sarcocysts first became grossly visible at PID 391 and sarcocysts from sheep first became infectious for cats at PID 230. PMID- 3084407 TI - Clostridial peritonitis associated with a mast cell tumor in a dog. AB - Recurrent peritonitis caused by Clostridium limosum was associated with a mast cell tumor of a cranial mesenteric lymph node in a dog. The diagnosis of mast cell tumor was obscured because of the peritonitis and the appearance and location of the mass, which resembled an abscess. Since clostridial infections frequently are associated with neoplasia in man, veterinarians should be aware of the possibility of a similar relationship in animals. PMID- 3084408 TI - Aortic diverticulum, ventricular septal defect, and increased bronchial markings in a dog. PMID- 3084409 TI - Immunodiagnosis of systemic mycoses in animals: a review. AB - Immunologic methods have been used with varying success in the diagnosis and prognosis of systemic mycoses in animals. Information on the application of the tests and on the interpretation of test results in monitoring therapy was complied. Serotesting provided diagnostic and prognostic data in immunocompetent patients, and predicted relapse in one case after apparent clinical cure. The tests were useful in the management of animals with mycoses that respond slowly and unpredictably to therapeutic agents for which pharmacologics and pharmacokinetics have not been established in domestic animals. Certain tests were not useful in some cases. PMID- 3084410 TI - High susceptibility of analbuminemic rats to gastric tumor induction by N-methyl N'-nitro-N-nitrosoguanidine. AB - Analbuminemic rats were found to be highly susceptible to induction of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine (67-83 micrograms/ml) given to the rats in drinking water for 32 weeks. The rats were sacrificed at experimental week 44. Gastric tumors were found in 12 of 17 analbuminemic rats (70%) and in 8 of 21 normal rats (38%). Intestinal tumors developed in 7 of 17 (41%) analbuminemic rats and in 9 of 21 (42%) normal rats. PMID- 3084411 TI - Des-O-methylolivoretin C is a new member of the teleocidin class of tumor promoters. AB - Des-O-methylolivoretin C, a demethylated form of olivoretin C, is a naturally occurring compound in Streptomyces mediocidicus and Streptoverticillium olivoreticuli. Des-O-methylolivoretin C is a regioisomer of teleocidin B, which has the same activity as teleocidin. The tumor-promoting activity of des-O methylolivoretin C was studied in a two-stage carcinogenesis experiment on mouse skin in comparison with that of teleocidin. Treatments with 7,12 dimethylbenz[a]anthracene (DMBA) plus des-O-methylolivoretin C and DMBA plus teleocidin induced tumors in 63.3% and 84.6% of the mice, respectively, in week 30. The difference in the tumor-promoting activities of des-O-methylolivoretin C and teleocidin is presumably related to the regioisomeric difference in the cyclohexene ring. PMID- 3084412 TI - Human placental form of glutathione S-transferase (GST-pi) as a new immunohistochemical marker for human colonic carcinoma. AB - Human placental form of glutathione S-transferase (GST-pi) was detected in human colonic carcinomas and adenomas by peroxidase anti-peroxidase method using antibody raised against GST-pi. Of 60 carcinomas, including differentiated adenocarcinomas and undifferentiated carcinomas, 88% were positive for GST-pi staining, and 47% of 23 adenomas were also positive. In the normal colonic mucosa, GST-pi was not detectable or was only weakly stained in the basal parts of the absorptive cells or in the cytoplasm of the cells containing little mucin. These results indicate that GST-pi is a possible new marker for immunohistochemical detection of human colonic carcinoma and some adenomas. PMID- 3084413 TI - Inhibitory effects of ethoxyquin, 4,4'-diaminodiphenylmethane and acetaminophen on rat hepatocarcinogenesis. AB - Four antioxidant species, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ethoxyquin and alpha-tocopherol, and three other compounds, 4,4'-diaminodiphenylmethane (DDPM), acetaminophen and glutathione, were tested for inhibitory effect on hepatocarcinogenesis in male F344 rats. Rats were initially given a single ip injection of diethylnitrosamine (200 mg/kg body weight) and fed basal diet containing 0.02% 2-acetylaminofluorene from week 2 to week 8. Animals were subjected to partial hepatectomy at the end of week 3. From week 12 to week 36, they were given basal diet containing 2% BHA, 1% BHT, 0.8% ethoxyquin, 1% alpha-tocopherol, 0.1% DDPM, 1% acetaminophen, or 1% glutathione, then killed at week 40, 4 weeks after cessation of treatment with the test chemicals. The incidence of hepatocellular carcinoma (HCC) was significantly decreased in the groups given ethoxyquin or DDPM. Quantitative analysis of the number and area of HCC per unit liver area revealed a significant decrease in the area of HCC in the groups given ethoxyquin, DDPM or acetaminophen. The results suggest that ethoxyquin, DDPM and acetaminophen exerted an inhibitory effect on the development of HCC, while BHA, BHT, alpha-tocopherol and glutathione had no significant effect. PMID- 3084414 TI - Immunohistochemical demonstration of induction of pyloric glands with low pepsinogen 1 (Pg 1) content in rat stomach by N-methyl-N'-nitro-N nitrosoguanidine. AB - Three groups of male Fischer rats were given single doses of N-methyl-N'-nitro-N nitrosoguanidine (MNNG) at 160 mg (group 1), 80 mg (group 2) and 40 mg (group 3)/kg body weight by gastric intubation. A fourth group was given drinking water containing 100 micrograms/ml of MNNG for 2 weeks, and a fifth group served as a control. Rats were killed in weeks 5, 8 and 12. Serial sections of the pyloric mucosa were examined by paradoxical concanavalin A (Con A) staining and pepsinogen isozyme 1 (Pg 1) immunostaining. All pyloric glands contained class III mucin as detected by paradoxical Con A staining. Most pyloric glands had a high Pg 1 content, but a few stained only weakly if at all. The percentage and number (No./500 normal-looking pyloric glands) of pyloric glands with a low Pg 1 content were 50.0 and 0.2 +/- 0.4 (week 5), 87.5 and 0.5 +/- 0.4 (week 8) and 100.0 and 1.2 +/- 1.0 (week 12) in group 1, 50.0 and 0.2 +/- 0.3 (week 8) and 87.5 and 0.5 +/- 0.4 (week 12) in group 2, and 30.0 and 0.2 +/- 0.4 (week 12) in group 4. No pyloric glands with a low Pg 1 content were found in groups 3 and 5. Thus the results showed significant dose-dependent induction (P less than 0.05 0.01) of altered pyloric glands demonstrating reduced Pg 1 content and their earlier appearance in groups given higher doses of MNNG. The results suggest that the appearance of pyloric glands with a low Pg 1 content may be a preneoplastic change in gastric carcinogenesis. PMID- 3084415 TI - Cellular mechanisms of transformation of BALB/3T3 A31-1-1 cells [corrected] by gamma-irradiation. AB - In order to clarify the mechanism of transformation, the effect of cell generation number on the time of appearance of transformed cells was examined in gamma-ray-irradiated BALB/3T3 A31-1-1 cells. The results showed that an increased number of cell generations (produced by seeding of cells at lower cell densities as well as under dispersed conditions) was important for increasing the rate of transformation. By a procedure in which irradiated cells in dishes were dispersed by trypsinization and recultured in the original dishes after cultivation for a certain number of days, we expected to establish the so-called "expression period." The rationale was that the number of transformed foci would increase after the appearance of a transformed cell due to its expansion. The expression period was shown to be 1.5 weeks on average. The time of appearance of transformed cells, however, varied from as early as about 1 week to 2.5 weeks. When cells were seeded at higher or lower cell densities and examined by the technique of dispersion and reculture, the expression periods were almost the same. Thus, it is probable that transformed cells can appear before or after the confluent state is reached. PMID- 3084416 TI - Production of immunoreactive calcitonin and some other tumor markers by established human carcinoma cell lines. AB - Out of seven human carcinoma cell lines (M7609, CCK-81, FCC-1, RPMI#4788, QGP-1, HLC-1, and KNS-62), 4 cell lines were found to produce immunoreactive calcitonin (ICT), a potential tumor marker for various malignancies. During a 7-day culture, 1.4 X 10(5) QGP-1, RPMI#4788, HLC-1, and KNS-62 cells secreted 7,000 pg, 500 pg, 400 pg, and 400 pg of ICT in the medium, respectively. The production of ICT by QGP-1 cells was increased by addition of pentagastrin or calcium gluconate. Three different components of ICT (peak I, molecular weight greater than 40,000; peak II, 14,000-18,000; peak III, 3,400) were detected by gel filtration of the QGP-1 spent medium. In a competitive inhibition-type radioimmunoassay of serial dilutions of each ICT component, peak III component showed very similar immunoreactivity to synthetic calcitonin. However, the other two components gave clearly different immunoreactivities from the peak III component and showed very similar immunoreactivities to each other. All the cell lines were further screened for synthesis of 7 other tumor markers, carcinoembryonic antigen, nonspecific cross-reacting antigen, CA19-9, tissue polypeptide antigen, alpha fetoprotein, beta 2-microglobulin and ferritin. Every cell line produced 2 to 6 markers concomitantly, and various combinations of positive markers were found among the cell lines. PMID- 3084417 TI - DNA ploidy patterns of minute carcinomas in the stomach. AB - DNA ploidy patterns of minute carcinomas in the stomach were determined by cytofluorometric measurement, using paraffin sections which had been prepared for histological examination. The examples studied were 19 minute carcinomas less than 5 mm in diameter, of which 12 were adenocarcinomas, and 7 were signet ring cell carcinomas. By measuring the fluorescence intensity of more than 30 mitotic nuclei, the DNA ploidy pattern of each tumor was determined. The control diploid DNA content was obtained by measuring the fluorescence intensity of non-cancerous mitoses in the gastric mucosa. In the present study, heteroploidy was seen in 5 carcinomas; 4 adenocarcinomas and one signet ring cell carcinoma. The remaining 14 carcinomas were composed of a diploid stem cell line. In 3 adenocarcinomas, polyploid cells were seen. The occurrence of heteroploidy in the minute cancers was similar to that found in advanced cancers, whereas polyploid cells appeared to occur less frequently in the minute cancers than in the advanced cancers. PMID- 3084418 TI - Ciliated metaplasia in the gastric mucosa. Studies on Japanese patients. AB - A total of 137 consecutive gastrectomy specimens from Japanese patients having either chronic peptic ulcer, focal (elevated) dysplasia or intramucosal carcinoma were scrutinized under high-power examination (X 1000) for the presence of ciliated cells. In 48 specimens (35.0%) ciliated cells were found in non neoplastic dilated pyloric glands. The highest percentage was found in cases with focal (elevated) dysplasia (42.6%) or intramucosal carcinomas of intestinal type (41.6%) and the lowest in cases with intramucosal carcinoma of the diffuse type (15.4%) or chronic peptic ulcer (16.0%). Ciliated cells in the gastric mucosa seem therefore to be a common phenomenon in Japanese subjects and appear to be a new indication that the gastric mucosa of Japanese patients may differ from the gastric mucosa of Europeans. PMID- 3084419 TI - The role of drinking and cigarette smoking in the excess deaths from liver cancer. AB - A long-term cohort study of 639 males in a farming area and 677 males in a fishing area in Kyushu, Japan, has been conducted to evaluate risk factors for ischemic heart disease. The present investigation utilized this long-term cohort study to assess the role of drinking and cigarette smoking habits in the causation of liver cancer. The O/E ratio (ratio of the observed to expected number of deaths) of liver cancer was 7.5 (P less than 0.001) among shochu drinkers in the fishing area. Further, a clear dose-response relationship of O/E ratio was noted: 5.7 (P less than 0.001), 7.5 (P less than 0.001) and 20.0 (P less than 0.001) for drinkers of less than 1, 1-2, and 2 or more units of shochu (a distilled alcoholic beverage made in Japan; about 25% alcohol). Although no excess risk was found among shochu drinkers in the farming area, observed and expected numbers were too small to make valid judgements. Among sake drinkers, the observed and expected numbers were very similar in both areas. Cigarette smokers in the fishing area appeared to have a high risk for liver cancer, the O/E ratio being 4.8 (P less than 0.001). However, there was no clear dose response relationship and O/E ratios among cigarette smokers according to their drinking habits indicated no excess risk among nondrinkers. A multiple logistic regression analysis showed an insignificant effect of cigarette smoking on the development of liver cancer after adjustment for shochu drinking. These findings suggest a significant involvement of shochu drinking in the etiology of liver cancer, at least in this fishing area. PMID- 3084420 TI - Risk factors of multiple primary cancers in breast cancer patients. AB - To clarify risk factors of multiple primary cancers in breast cancer patients, a case-control analysis based on data from medical records was conducted at the Aichi Cancer Center Hospital. For each of a total of 115 multiple primary cancer patients affected by one or two other primary cancers after or concurrently with breast cancer, two patients with unilateral breast cancer were selected as controls by matching age, time of the operation for breast cancer, and survival period. Multiple primary cancer patients were then divided into two groups, 61 cases of bilateral breast cancer and 56 cases of other multiple primary cancers. Conditional multiple logistic regression analysis indicated that relatively heavy smoking (more than 10 cigarettes per day) decreased the risk of multiple primary cancers taken overall (relative risk (RR) = 0.23); overweight status elevated the risk of bilateral breast cancer (RR = 3.01); and greater than average height (RR = 2.20), history of gallstone or cholecystitis (RR = 6.29), and late first birth or nulliparous status (RR = 6.85) elevated the risk of other multiple primary cancers. The effects of weight and height were predominant in the postmenopausal women. As to family history, we could not obtain clear results, though history of cancer among siblings tended to increase the risk of multiple primary cancers (P less than 0.10) and family history of breast cancer was more frequent in patients with bilateral breast cancer (not significant). PMID- 3084422 TI - Chimeric potency of a mutator strain of mouse teratocarcinoma cells. AB - The developmental potential of a mutator strain Ara Cr (1.5)4 of mouse teratocarcinoma cells was examined by injecting these cells into host blastocysts. Analysis of developing embryos at 9.5 days of gestation showed the mutator strain gave chimeras at a rate comparable with that of the parent strain. However, most of these chimeric embryos with the mutator strain were abnormal, and the extent of abnormality seems to be related to the proportion of the mutator-derived cells in the embryos. When injected embryos were allowed to develop to 14.5 days, the number of developing embryos decreased, and only a few were chimeric in limited tissues. The results suggest that the mutator strain is lethal to early gestational development, and only those chimeras with limited colonization of the strain can develop normally beyond this stage. PMID- 3084421 TI - Antitumor effect of two-drug simultaneous or sequential use of cisplatin, vindesine or etoposide on human pulmonary adenocarcinoma cell lines in tumor clonogenic assay. AB - The antitumor effects of two-drug simultaneous or sequential use of cisplatin, vindesine or etoposide were examined in human pulmonary adenocarcinoma cell lines by human tumor clonogenic assay. Different tumor cell lines (PC-9, PC-13 and PC 14) that originated from the same histological cell type responded quite variably to simultaneous and/or sequential therapy. The antitumor effects of various sequential combinations of cisplatin, vindesine and etoposide depended strongly on the nature of the individual tumor cell line tested. PMID- 3084423 TI - Interstitial deletion of the short arm of chromosome 6 as a new cytogenetic marker of T-cell lymphoma. AB - Three patients with malignant lymphoma, two of T-cell type and the other probably also of T-cell type, had an interstitial deletion of the short arm of chromosome 6, del (6)(p21p23), in common in their lymphoma cells. These findings suggest that this new type of chromosome deletion may be a specific marker for T-cell lymphoma and may play an important role in the lymphomagenesis and the expression of the T-cell phenotype. PMID- 3084424 TI - Promoting action of glycerol in pulmonary tumorigenesis model using a single administration of 4-nitroquinoline 1-oxide in mice. AB - This study was carried out to clarify the promoting effect of glycerol on 4-nitro quinoline 1-oxide (4NQO) tumorigenesis in the lung. Animals used were 80 ddY male mice, 6 weeks old. 4NQO, dissolved in olive oil-cholesterol (20:1) mixture, was injected subcutaneously at a dose of 10 mg/kg body weight per mouse. Drinking water contained 5% glycerol. Mice were divided into the following 4 groups of 20 animals each: non-treated mice (group I), mice given glycerol alone (group II), mice given 4NQO alone (group III), mice receiving combined administration of 4NQO and glycerol (group IV). The percent of mice having induced pulmonary tumors and the mean number of tumors per mouse were 2 and 0.10 +/- 0.07 (mean +/- SE), 2 and 0.10 +/- 0.07, 9 and 0.45 +/- 0.25, and 58 and 2.90 +/- 0.62, respectively. A significantly higher rate was seen in group IV, as compared with the 4NQO-treated control. This result showed that glycerol has a promoting action on 4NQO-induced pulmonary tumorigenesis in mice. PMID- 3084425 TI - Inhibitory effects of polyprenoic acid (E-5166) on N-2-fluorenylacetamide initiated hepatocarcinogenesis in rats. AB - The effects of the newly synthesized polyprenoic acid, 3,7,11,15-tetramethyl 2,4,6,10,14-hexadecapentaenoic acid (E-5166) on N-2-fluorenylacetamide (FAA) initiated hepatocarcinogenesis were examined in 6 groups of male ACI rats. The numbers of altered hepatocellular foci in rats of group 1 given a basal diet containing 0.02% FAA for 13 weeks and in rats of group 2 which received E-5166 by gavage (40 mg/kg, 3 times/week) at the same time as receiving the FAA diet were almost the same, indicating that E-5166 had no effect at the stage of carcinogen exposure. However, the number of foci in group 4, in which rats were given the basal diet and E-5166 after the termination of the carcinogen exposure, and were sacrificed 16 weeks later, was significantly smaller than that in group 3 maintained on the basal diet alone (P less than 0.05). The results suggests some anticarcinogenic activity of E-5166, possibly involving the phenotypic expression of the preneoplastic foci. Furthermore, the number of altered foci in rats of group 6 (given the liver-tumor promoter phenobarbital with E-5166 for 16 weeks after the administration of carcinogen) was also significantly smaller than that in rats of group 5, which received the promoter (P less than 0.05). The incidence of neoplastic nodules of the liver in group 6 at the end of the experiment was also lower than in group 5 (P less than 0.0014). These results suggest an antipromoting effect of the polyprenoic acid E-5166 on rat chemical hepatocarcinogenesis. PMID- 3084426 TI - Metabolism of 1-nitropyrene in germ-free and conventional rats. AB - The distribution, covalent binding and metabolism of radioactive 1-nitropyrene (1 NP) were examined following its oral administration to conventional and germ-free male Wistar rats. With both groups of animals, the liver, kidney, bladder, adipose tissue and gastrointestinal tract had the highest specific radioactivity. However, the maximum concentration of radioactivity occurred at 12 hr in conventional rats as compared to 24 hr in germ-free animals. This difference may be due to the faster transit time of the intestinal contents through conventional rats. At 48 hr after treatment, the covalent binding of 1-NP metabolites was greatest in liver and kidney of conventional rats, while in germ-free rats, substantial binding was also found in the gastrointestinal tract. The mutagenic activity in Salmonella typhimurium TA98 of fecal extracts and urine from conventional rats was greater in the presence of an S9 mix, whereas similar extracts from germ-free animals were more mutagenic in the absence of S9. The major fecal metabolites in germ-free rats were (in order of decreasing concentration): 3-nitropyrenol greater than 1-NP greater than 4,5-dihydroxy-4,5 dihydro-1-NP greater than 6-nitropyrenol greater than 8-nitropyrenol. With the exception of 1-NP, similar metabolites were found in the urine as their glucuronide conjugates. In the feces from conventional rats, substantial nitro reduction and N-acetylation occurred with the major metabolites being: 1-NP greater than 1-aminopyrene greater than 8-acetylaminopyrenol greater than 6 acetylaminopyrenol greater than 3-acetylaminopyrenol. The major metabolites identified in the urine from conventional rats were glucuronide conjugates of 6- and 8-acetylaminopyrenol, while the major biliary conjugates identified were glucuronide conjugates of 4,5-dihydroxy-4,5-dihydro-1-NP and 3-, 6-, and 8 nitropyrenol, although the relative proportion of glucuronide conjugates of 6- and 8-aminopyrenol and 6- and 8-acetylaminopyrenol increased in later stages of the biliary excretion. The polar and beta-glucuronidase-refractory metabolites, which may be sulfate and glutathione conjugates, remain to be identified. PMID- 3084427 TI - Cytological evidence for single-cell origin of tumors induced with 3 methylcholanthrene in female mice carrying Cattanach's translocation. AB - Chromosome studies were carried out on 12 tumors induced by subcutaneous injection of 0.005-0.5 mg of 3-methylcholanthrene in female mice carrying Cattanach's X-autosome translocation. Using the asynchronously replicating (hence genetically inactive) X chromosome as a marker, we obtained evidence showing that most or all of these tumors were monoclonal in origin. A single case, in which cell fusion occurred early in tumorigenesis, demonstrated that simultaneous expression of two different X chromosomes is not always incompatible with monoclonality. PMID- 3084428 TI - Cytogenetic effects of etoposide (VP-16) on human lymphocytes; with special reference to the relation between sister chromatid exchange and chromatid breakage. AB - The effects of etoposide (VP-16) on sister chromatid exchange (SCE) and chromosome abnormalities were studied by using human peripheral lymphocytes. This drug produced a significant increase in the SCE frequency and chromosomal aberrations such as breaks, exchanges, and tetraploidy with or without endoreduplication. Analysis of the breakpoints of chromatid deletion with respect to their association with SCE in the metaphases from the second division demonstrated that VP-16-induced deletions arose with little dependence on the site of SCE. It is suggested that chromatid deletions induced by this drug derive from unrepaired chromatid breaks rather than from incomplete exchanges. PMID- 3084429 TI - Volume regulation in leukemic and lymphoma cells in children and determination of cell lineage. AB - Among normal lymphocytes, T cells can readjust their volume rapidly following initial swelling in a hypotonic medium, whereas B cells do not have this ability. Based on this finding, we examined the volume regulation of malignant cells from 40 patients with lymphocytic and nonlymphocytic malignancies. The T lineage cells were able to regulate their volume in response to hypotonic stress, whereas B lineage cells were not able to do so. In contrast to lymphoid lineage cells, nonlymphocytic leukemia cells as well as undifferentiated cells did not show a consistent tendency in their volume regulation. These results showed that the difference in the ability to regulate cell volume in response to hypotonic stress is available as a marker for identifying the cellular lineage of lymphoid malignancies. PMID- 3084430 TI - Evaluation of the efficacy of mass screening for uterine cancer in Japan. AB - To evaluate epidemiologically the efficacy of mass screening for uterine cancer, we compared the changes in the age-adjusted death rates from cancer of the uterus from 1969-1972 to 1973-1977 between the high coverage-rate areas and the control areas. The main results were: the decrease in the average age-adjusted death rate from cancer of the uterus was greater in the overall high coverage-rate (20% and over) areas (33.4%) than in the control areas (26.9%), but this difference was not statistically significant, when the high coverage-rate areas were limited to those where the uterine cancer death rate in 1969-1972 was greater than 90% of the average rate of all Japan, the decrease in the average age-adjusted death rate from cancer of the uterus was also greater in these high coverage-rate areas (68.1%) than in the control areas (44.2%) and this difference was statistically significant (P less than 0.01), when the high coverage-rate areas were limited to municipalities with a population size larger than 5,000, similar trends were observed. These results suggested that if mass screening for uterine cancer is widely conducted in areas with relatively high mortality rate from uterine cancer, it may be possible to reduce the mortality from this cancer at the community level. PMID- 3084431 TI - Effects of Nocardia rubra cell wall skeleton on interleukin 2 production and lymphocyte proliferation in former poison gas factory workers. AB - Phytohemagglutinin (PHA)-induced interleukin 2 (IL-2) production and lymphocyte proliferation were measured in former workers of the Okunojima Poison Gas Factory (poison gas workers), who have a high incidence of lung cancer, and the efficacy of administration of Nocardia rubra cell wall skeleton (N-CWS) was studied. In comparison with normal controls and poison gas workers receiving N-CWS, lymphocyte proliferation in poison gas workers not receiving N-CWS showed a significant decrease, while IL-2 production showed a slight though not statistically significant decrease. When N-CWS was administered to poison gas workers, IL-2 production and lymphocyte proliferation were significantly elevated, with a peak two weeks after administration. N-CWS, by elevating IL-2 production of lymphocytes, is considered to have improved the depression of lymphocyte proliferation. PMID- 3084432 TI - Antitumor effect of recombinant human interferon alpha A/D on Meth-A sarcoma in mice. AB - Recombinant human interferon alpha A/D (IFN alpha A/D) is known to be as active on murine cells as on human cells. We studied the antitumor effect of pure IFN alpha A/D on Meth-A sarcoma subcutaneously transplanted into female syngeneic BALB/c mice. When administered systematically (intraperitoneally), IFN alpha A/D was only marginally (but significantly, P less than 0.05) effective in inhibiting tumor growth. With intralesional injection, however, IFN alpha A/D strongly suppressed the growth of Meth-A sarcoma, even leading to complete tumor regression and to subsequent immunity to Meth-A sarcoma cells in the host mice when the treatment was started early after tumor transplantation and with a high IFN alpha A/D dose. We also found that treatment of mice with IFN alpha A/D increased the level of serum alpha 1-acid glycoprotein, one of the acute-phase proteins. PMID- 3084433 TI - Effects of a new fluorinated macrolide (P-0501A) and other erythromycins on drug metabolizing enzymes in rat liver. AB - The effects of a new fluorinated macrolide (P-0501A) on drug metabolizing enzymes of rat liver were compared with three erythromycins--the base, the stearate and the estolate--after 7 days of dosing (1.36 mmol/kg po daily). The three erythromycins induced the synthesis of microsomal enzymes, but the products of their metabolism inactivated cytochrome P-450 in the order base less than or equal to stearate less than estolate. N-Demethylation of erythromycin and aminopyrine increased, while O-demethylation of 4-nitroanisole was reduced and hydroxylation of aniline was not changed after in vivo treatment. Pentobarbital sleeping time was prolonged and liver glutathione levels were lower in treated rats than in controls. In contrast to the three erythromycins, P-0501A did not induce the synthesis of microsomal enzymes, did not form an inactive complex with cytochrome P-450 and did not affect mono-oxygenase activities or pentobarbital narcosis. PMID- 3084434 TI - D-beta-lysylmethanediamine, a new biogenetic amine produced by a Streptomyces. PMID- 3084435 TI - [14C]-aflatoxin B1 metabolism in lactating goats and rats. AB - Four dairy goats in the second to third month of lactation were administered [14C]-Aflatoxin B1 ( [14C]-AFB1). Two goats were dosed intravenously (iv) with 130 muCi (182 muCi/mumol) and two were dosed orally with 196 muCi (256 muCi/mumol). Urine, milk and feces were collected for 120 h after [14C]-AFB1 administration. Recoveries (average of two animals) of 14C in urine, milk and feces were, respectively; 22.7, .97 and 65% (iv dose) and 30.9, 1.05 and 52.3% (oral dose). Aflatoxin M1 (AFM1) was found in milk in the highest concentration. Aflatoxin Q1 (AFQ1) and aflatoxicol (AFL) were found in trace quantities in milk of animals administered the oral dose. In general, AFM1 could account for the majority of dicholromethane-soluble 14C. Liver contained 7.3 and 4.9% of the dose after 120 h for the iv and oral doses respectively. Kidney, heart, lung and spleen all contained .1% or less of the dose at 120 h. Muscle contained .48% of the dose at 120 h from the goats administered [14C]-AFB1 orally. There was no detectable radioactivity in the fat of any goat at 120 h. Six lactating Sprague Dawley rats with 12 nursing pups were used for comparison of ruminants and simple stomached animals. Rats were administered 2 muCi of [14C]-AFB1 (125 muCi/mumol) iv (three animals) and orally (three animals). Mean recovery of 14C in urine, mammary plus milk and feces were, respectively; 9.5, 2.0 and 60.7% (iv) and 8.8, 2.6 and 65.0% (orally).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084436 TI - Follicular fluid concentrations of estradiol-17 beta and progesterone and secretory patterns of LH and FSH in prepubertal gilts reared in confinement or outdoor lots. AB - One-hundred-twenty crossbred gilts from two experiments were assigned randomly to a 2 X 5 factorial experiment. Gilts were reared in two environments (confinement or outside) and assigned to be slaughtered at 4, 5, 6, 7 or 8 mo of age. Beginning at 6 mo of age, blood samples were taken at weekly intervals from each gilt via venipuncture. Serum concentrations of progesterone were analyzed to determine when gilts attained puberty. On the day prior to slaughter, six pigs within a treatment group were cannulated and blood samples were taken at 20-min intervals for 4 h. At slaughter, follicular fluid (FF) was aspirated and the volume determined from those follicles having a diameter of at least 4 mm. No effect of environment was found on the proportion of gilts that attained puberty by 8 mo of age. For the 12 gilts that reached puberty during the study, the age at puberty for gilts reared in outdoor lots (202 +/- 5 d) was less (P less than .05) than those reared in confinement (224 +/- 8 d). Mean concentrations of serum luteinizing hormone (LH; P = 98) and number of secretory spikes of LH (P = .76) were similar between gilts reared in confinement and those reared in outdoor lots. No differences in average serum concentrations of follicle stimulating hormone (FSH) or number of secretory spikes of FSH were found between gilts subjected to these environments (P = .95). Concentrations of estradiol-17 beta in FF were not affected by environment or age (P greater than .25).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084437 TI - Ruminal evacuation's effect on microbial activity and ruminal function. AB - The influence of evacuating, mixing and returning ruminal contents on microbial populations, volatile fatty acid (VFA) concentrations and liquid flow rate was investigated with four ruminal-cannulated Hereford steers (247 kg avg wt). Ruminoreticular contents were sampled, then completely removed, mixed for 5 min and returned to the rumen. Subsequent samples were taken immediately, 1 h and 4 h later. Non-evacuated steers were sampled at identical time intervals either 1 d before or after evacuation. Averaged over time, there was no significant difference between evacuated and non-evacuated steers in total anaerobic, cellulolytic and facultative bacteria, protozoa, oxidation-reduction potential, VFA concentrations, and liquid flow rates. There were no treatment X time interactions and, except for holotrich protozoa and VFA, no differences from time of sampling. Ruminal evacuation does not appear disruptive to anaerobiosis or detrimental to ruminal microorganisms and digestive processes. PMID- 3084439 TI - Polyamine inhibitors. PMID- 3084438 TI - Characteristics of staphylococci isolated from man, poultry and some other animals. AB - Of 281 strains of staphylococci isolated from man and animals 36 (12.8%) were coagulase-positive and 245 (87.2%) were coagulase-negative. Staphylococcus aureus and Staph. intermedius were the commonest coagulase-positive staphylococci isolated from the hosts examined. Of the 20 strains that remained unclassifiable, 14 were isolated from sheep and goats. PMID- 3084440 TI - Macrolide, lincosamide and streptogramin resistance in Campylobacter jejuni/coli. AB - Strains of erythromycin-resistant Campylobacter jejuni/coli isolated in the United Kingdom, Canada and Europe, were also resistant to tylosin, spiramycin and clindamycin and, like sensitive strains, were insensitive to virginiamycin and pristinamycin component B. These were designated as macrolide-lincosamide streptogramin generalized resistant organisms and macrolide-lincosamide generalized resistant on the basis of patterns of resistance to pristinamycin components A and B. Two erythromycin-sensitive strains whose resistance to spiramycin and tylosin had been produced in the laboratory showed cross resistance to erythromycin, but were still sensitive to clindamycin. These were characterized as macrolide-streptogramin A inducible resistant organisms. The isolates tested were identified and all were found to be C. coli, except for two strains, one erythromycin-resistant and one erythromycin-sensitive, which hydrolyzed hippurate and were thus identified as C. jejuni. PMID- 3084441 TI - Effects of ethylenediaminetetraacetic acid and gentamicin on the antibacterial activity of pyridone carboxylic acid derivatives against gram-negative bacilli. AB - Ofloxacin (9-fluoro-3-methyl-10-(4-methyl-1-piperazynyl)-7-oxo-2,3-dihydro-7 H pyrido-(1,2,3-de)1,4-benzoxazine-6-carboxylic acid) and enoxacin (1-ethyl-6 fluoro-1,4-dehydro-4-oxo-7-(1-piperazinyl)-1, 8-naphthyridine-3-carboxylic acid) are newly developed pyridone carboxylic acid derivatives with broad and potent antibacterial activities against Gram-negative and Gram-positive bacteria. Antibacterial activities of six pyridone carboxylic acid derivatives, including these two new antibiotics, were examined against Gram-negative bacilli in the presence and absence of ethylenediaminetetraacetic acid (EDTA) or gentamicin. The minimal inhibitory concentrations (MICs) of nalidixic acid, cinoxacin and piromidic acid were reduced by the addition of EDTA or gentamicin. However, the MICs of pipemidic acid, ofloxacin and enoxacin were unaffected. These findings indicated the high permeability of pipemidic acid, ofloxacin and enoxacin through the outer membrane. The effects of EDTA and gentamicin against Serratia marcescens were different from those against other Gram-negative bacilli. PMID- 3084442 TI - Elimination of nasal carriage of Staphylococcus aureus with mupirocin ('pseudomonic acid')--a controlled trial. AB - In a blind controlled trial 2% mupirocin ointment was applied four times a day for five days to the anterior nares of 32 healthy volunteers who were followed-up for at least five weeks. Mupirocin eliminated the persistent carriage of Staphylococcus aureus in all subjects within two days of starting mupirocin. Two weeks after the course S. aureus could not be detected, even in low numbers, in nose swabs from any of the 32 volunteers, and even after five weeks only six had resumed carriage. Of the 14 subjects who ultimately resumed carriage, 57% acquired a different phage type and 29% showed a relapse of colonisation with their pre-treatment strain. There was no evidence of overgrowth with Gram negative organisms and pre- and post-treatment isolates of S. aureus were sensitive to mupirocin with MICs of 0.06 mg/l or less. There were no side effects. We suggest that mupirocin may become the topical agent of choice for the elimination of S. aureus from the anterior nares. PMID- 3084443 TI - Lactate extraction during net lactate release in legs of humans during exercise. AB - Lactate metabolism was studied in six normal males using a primed continuous infusion of lactate tracer during continuous graded supine cycle ergometer exercise. Subjects exercised at 49, 98, 147, and 196 W for 6 min at each work load. Blood was sampled from the brachial artery, the iliac vein, and the brachial vein. Arteriovenous differences were determined for chemical lactate concentration and L-[1-14C]-lactate. Tracer-measured lactate extraction was determined from the decrease in lactate radioactivity per volume of blood perfusing the tissue bed. Net lactate release was determined from the change in lactate concentration across the tissue bed. Total lactate release was taken as the sum of tracer-measured lactate extraction and net (chemical) release. At rest the arms and legs showed tracer-measured lactate extraction, as determined from the isotope extraction, despite net chemical release. Exercise elicited an increase in both net lactate release and tracer-measured lactate extraction by the legs. For the legs the total lactate release (net lactate release + tracer measured lactate extraction) was roughly equal to twice the net lactate release under all conditions. The tracer-measured lactate extraction by the exercising legs was positively correlated to arterial lactate concentration (r = 0.81, P less than 0.001) at the lower two power outputs. The arms showed net lactate extraction during exercise, which was correlated to the arterial concentration (r = 0.86). The results demonstrate that exercising skeletal muscle extracts a significant amount of lactate during net lactate release and that the working skeletal muscle appears to be a major site of blood lactate removal during exercise. PMID- 3084444 TI - Radial and longitudinal compartmental analysis of gas transport during high frequency ventilation. AB - A model of gas exchange by low-tidal-volume (VT), high-frequency ventilation (HFV) is presented, based on the physical principles of dispersion. These are the nonuniformity of the velocity profile and the nonreversible mixing of fluid components in a diffusive manner. A numerical method was used to incorporate these principles into a quantitative model. The airways of a symmetrically bifurcating bronchial-tree model were partitioned in the radial direction into two concentric layers representing the kinematic dispersion by nonuniformity of the velocity profile. Mixing between the layers was invoked in proportion to the diffusivity and local dimensions. The effects of frequency (f), VT, shape of the velocity profile, and bronchial-model configuration were tested in the model, with favorable comparison to available experimental data. The model predicts that for a frequency-dependent velocity profile, the rate of tracer exchange is proportional to the square root of f and to the square of VT-V0, where V0 is a constant small volume under which gas exchange was nil. Intracycle asymmetric mixing is predicted to have a stronger effect on gas exchange than asymmetric velocity profile. Gas exchange when turbulent-flow regime is assumed is predicted to be less for the higher VT values than with laminar flow and with mixing by molecular diffusivity. This model was found to be didactic, flexible, and capable of modeling combinations of factors affecting either one of the two fundamental processes of dispersion. PMID- 3084445 TI - Transvascular clearance and distribution of charged macromolecules in ANTU lung injury. AB - Tissue uptake, extravascular distribution volumes, and plasma-lymph equilibration of two isozymes of lactate dehydrogenase (LDH) were labeled with radioiodine and studied in dogs with either normal or injured lungs. Cationic LDH 5 [isoelectric point (pI) = 7.9] was initially cleared from plasma by lung tissue at a rate 1.61 times higher (9.3 vs. 5.8 X 10(-3) ml X min-1 X g-1 extravascular wet wt) than anionic LDH 1 (pI = 5.0). LDH 5 also had a significantly higher extravascular distribution volume but equilibrated more slowly between plasma and pulmonary lymph (t1/2 = 120 min) than LDH 1 (t1/2 = 78 min) in normal lungs. Respective lymph-to-plasma ratios were 0.53 and 0.43 for LDH 1 and LDH 5 after 4 h of infusion. Infusion of the isozymes 2 h after injection of alpha-naphthylthiourea (ANTU) resulted in larger initial tissue plasma clearances for both isozymes compared with control, but greater relative tissue plasma clearances and extravascular distribution volumes for LDH 5 compared with LDH 1. Plasma-lymph equilibration half times of LDH 5 and LDH 1 were reduced after ANTU to 50 min and 41 min, respectively, whereas the respective alveolar fluid-to-plasma ratios of the two isozymes at termination of the ANTU experiments were 0.56 and 0.84. These data suggest that the fixed anionic charges on endothelial cell surfaces, intercellular junctions, basement membranes, and interstitial structures act much like a cation exchange gel to rapidly take up cationic proteins and retard the plasma-lymph equilibration of these proteins relative to anionic proteins of the same size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084446 TI - Systemic hemodynamics affecting cardiac output during hypocapnic and hypercapnic hypoxia. AB - Systemic hemodynamic adjustments involved in the control of cardiac output (CO) were examined in chronically instrumented unanesthetized sheep inhaling gas mixtures resulting in hypocapnic hypoxia (H) [arterial pH (pHa) = 7.53, arterial partial pressure of O2 (Pao2) = 30 Torr, arterial partial pressure of CO2 (Paco2) = 29 Torr] or hypercapnic hypoxia (HCH) (pHa = 7.14, Pao2 = 34 Torr, Paco2 = 72 Torr) for 1 h. H (n = 7) and HCH (n = 6) resulted in 26% and 61% increases in CO, respectively, and mean systemic arterial pressure rose to a greater extent during HCH. Both H and HCH resulted in increased blood flow (microsphere method) to the peripheral systemic circulation including the brain, heart, diaphragm, and nonrespiratory skeletal muscle (the latter blood flow increased 120% during H and 380% during HCH). Gastrointestinal and renal blood flow remained unchanged during H and HCH. Transit time of green dye from the pulmonary artery to regional veins in the hindlimb and intestine was 5.0 and 8.2 s, respectively, during base-line conditions and remained unchanged with HCH. During HCH, regional O2 consumption increased 274% for the hindlimb and decreased 39% for the intestine. Total catecholamines rose 250% during H and 3,700% during HCH. During hypocapnic and hypercapnic hypoxia, CO is augmented in part by systemic hemodynamic adjustments that include a redistribution of blood flow and a translocation of blood volume to the fast transit time peripheral systemic circuit. The sympathetic nervous system may play an important role in mediating these systemic hemodynamic adjustments. PMID- 3084447 TI - Effect of tracer infusion site on measurement of bicarbonate-carbon dioxide metabolism in dogs. AB - Ten dogs were given a primed infusion of H13CO3- for 220 min while under general anesthesia. Isotopic steady state was reached within 60 min in exhaled CO2, femoral arterial blood HCO3-, and femoral venous blood HCO3-. Halfway through each infusion study, the site of tracer infusion was changed either from the central aorta to a peripheral vein, or vice versa. The mean HCO3(-)-CO2 flux measured from blood HCO3- enrichments was 15.7 +/- 2.1 (SD) mmol X kg-1 X h-1. The mean fraction of tracer recovered in exhaled CO2 was 79 +/- 7% (SD) of the infused dose. No significant difference in either HCO3- flux or recovery of tracer was found between the venous and arterial infusions of tracer. These results indicate that when venous administration of HCO3- tracer is compared with central arterial infusion, the initial loss of tracer into expired CO2 is an unimportant consideration in experiments measuring HCO3- kinetics. PMID- 3084448 TI - O3-induced change in bronchial reactivity to methacholine and airway inflammation in humans. AB - The increase in airway responsiveness induced by O3 exposure in dogs is associated with airway epithelial inflammation, as evidenced by an increase in the number of neutrophils (polymorphonuclear leukocytes) found in epithelial biopsies and in bronchoalveolar lavage fluid. We investigated in 10 healthy, human subjects whether O3-induced hyperresponsiveness was similarly associated with airway inflammation by examining changes in the types of cells recovered in bronchoalveolar lavage fluid obtained after exposure to air or to O3 (0.4 or 0.6 ppm). We also measured the concentrations of cyclooxygenase and lipoxygenase metabolites of arachidonic acid in lavage fluid. We measured airway responsiveness to inhaled methacholine aerosol before and after each exposure and performed bronchoalveolar lavage 3 h later. We found more neutrophils in the lavage fluid from O3-exposed subjects, especially in those in whom O3 exposure produced an increase in airway responsiveness. We also found significant increases in the concentrations of prostaglandins E2, F2 alpha, and thromboxane B2 in lavage fluid from O3-exposed subjects. These results show that in human subjects O3-induced hyperresponsiveness to methacholine is associated with an influx of neutrophils into the airways and with changes in the levels of some cyclooxygenase metabolites of arachidonic acid. PMID- 3084449 TI - Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness. AB - Persons with acute altitude sickness hypoventilate at high altitude compared with persons without symptoms. We hypothesized that their hypoventilation was due to low initial hypoxic ventilatory responsiveness, combined with subsequent blunting of ventilation by hypocapnia and/or prolonged hypoxia. To test this hypothesis, we compared eight subjects with histories of acute altitude sickness with four subjects who had been asymptomatic during prior altitude exposure. At a simulated altitude of 4,800 m, the eight susceptible subjects developed symptoms of altitude sickness and had lower minute ventilations and higher end-tidal PCO2's than the four asymptomatic subjects. In measurements made prior to altitude exposure, ventilatory responsiveness to acute hypoxia was reduced in symptomatic compared to asymptomatic subjects, both when measured under isocapnic and poikolocapnic (no added CO2) conditions. Diminution of the poikilocapnic relative to the isocapnic hypoxic response was similar in the two groups. Ventilation fell, and end-tidal PCO2 rose in both groups during 30 min of steady-state hypoxia relative to values observed acutely. After 4.5 h at 4,800 m, ventilation was lower than values observed acutely at the same arterial O2 saturation. The reduction in ventilation in relation to the hypoxemia present was greater in symptomatic than in asymptomatic persons. Thus the hypoventilation in symptomatic compared to asymptomatic subjects was attributable both to a lower acute hypoxic response and a subsequent greater blunting of ventilation at high altitude. PMID- 3084450 TI - Naturally occurring Staphylococcus epidermidis plasmid expressing constitutive macrolide-lincosamide-streptogramin B resistance contains a deleted attenuator. AB - A naturally occurring constitutive macrolide-lincosamide-streptogramin B (MLS) resistance plasmid, pNE131, from Staphylococcus epidermidis was chosen to study the molecular basis of constitutive expression. Restriction and functional maps of pNE131 are presented along with the nucleotide sequence of ermM, the gene which mediates constitutive MLS resistance. Sharing 98% sequence homology within the 870-base-pair Sau3A-TaqI fragment, ermM appears to be almost identical to ermC, the inducible MLS resistance determinant from S. aureus (pE194). The two genes share nearly identical sequences, except in the 5' promoter region of ermM. Constitutive expression of ermM is due to the deletion of 107 base pairs relative to ermC; the deletion removes critical sequences for attenuation, resulting in constitutive methylase expression. PMID- 3084451 TI - Reversible regulation of the nitrogenase iron protein from Rhodospirillum rubrum by ADP-ribosylation in vitro. AB - Nitrogenase activity in the photosynthetic bacterium Rhodospirillum rubrum is reversibly regulated by interconversion of the Fe protein between a modified and an unmodified form. Since the discovery of the activation process in 1976, investigators have been unable to demonstrate the inactivation (modification) reaction in vitro. In this study, NAD-dependent modification and concomitant inactivation of the Fe protein were demonstrated in crude extracts of R. rubrum. Activation of the in vitro-modified Fe protein by activating enzyme and structural similarity between the in vivo and in vitro modifications are presented as evidence that the in vitro modification is the physiologically relevant ADP-ribosylation reaction. Using a partially purified preparation, we showed that the inactivating enzyme activity is stimulated by divalent metal ions and ADP, that O2-denatured Fe protein will not serve as a substrate, and that dithionite inhibits the modification reaction. PMID- 3084452 TI - Cloning of the gene for indoleacetic acid-lysine synthetase from Pseudomonas syringae subsp. savastanoi. AB - The phytopathogen Pseudomonas syringae subsp. savastanoi incites the production of galls on olive and oleander plants. Gall formation is dependent on bacterial production of the phytohormone indoleacetic acid (IAA). The genetic determinants for IAA synthesis are located on a plasmid (pIAA) and are organized in an operon in oleander strains of the bacterium. P. syringae subsp. savastanoi further converts IAA to an amino acid conjugate, 3-indole-acetyl-epsilon-L-lysine (IAA lysine). The gene for IAA-lysine synthetase (iaaL) was found on the IAA plasmid by screening pIAA deletion mutants for the ability to convert IAA to IAA-lysine. The iaaL locus was then cloned in the vector pUC8 from a bank of P. syringae subsp. savastanoi EW2009 plasmid DNA to construct recombinant plasmid pLG87. The specific activity of IAA-lysine synthetase in Escherichia coli transformed with pLG87 was 47 times higher than that of the enzyme extract from P. syringae subsp. savastanoi. The direction of transcription of the iaaL gene was determined to be opposite to that of the IAA operon. The location of the iaaL gene on pIAA1 was mapped by Tn5 insertion mutagenesis to a 2.5-kilobase-pair fragment 2 kilobase pairs from the IAA operon. PMID- 3084453 TI - Interaction of fructose with the glucose permease of the cyanobacterium Synechocystis sp. strain PCC 6803. AB - Fructose was bactericidal for the cyanobacterium Synechocystis sp. strain PCC 6803. Each of ten independently isolated fructose-resistant mutants had an alteration of the glucose transport system, measured as uptake of glucose or of 3 O-methyl-D-glucose. In the presence of the analog, the wild-type Synechocystis strain was protected against fructose. Two mutants altered in photoautotrophy were also isolated. PMID- 3084454 TI - A hypergraphic syndrome of automatic writing, affective disorder, and temporal lobe epilepsy in two patients. AB - Two patients are described who wrote complex textual material suddenly, automatically, and without volitional control. Each met DSM-III criteria for a major affective disorder, had clinical and electrophysiologic temporal lobe epilepsy, absence spells, episodic expressive aphasia, and a history of traumatic loss of consciousness. The episodes of automatic writing met the criteria for ictal events. These patients may have experienced an ictal analogue of interictal hypergraphia. The behavioral neurologic features of this syndrome are discussed in relation to its clinical presentation and known disorders of writing. PMID- 3084455 TI - Lithium treatment of hyperthyroidism and mania. AB - A case of a man who was admitted to the hospital with both mania and hyperthyroidism is presented to illustrate the interactions between affective disorder and thyroid function. In addition, the methods in which lithium carbonate affects thyroid function, thus making diagnosis more difficult, are discussed. The authors suggest guidelines for evaluation and management of similar patients. PMID- 3084456 TI - Effect of plasmapheresis on E-rosette receptors in SLE patients. AB - The present study reports on the effects of plasmapheresis on both cellular (E rosette receptor- and Fc receptor-bearing lymphocytes) and humoral (antilymphocyte antibodies) immunity in patients with active SLE. Ten untreated patients were studied before and after two plasma exchanges. The E-rosette receptor-positive cells were studied by OKT11 monoclonal antibody and Fc receptor bearing cells by Leu15 monoclonal antibody. Antilymphocyte antibodies were studied before and after plasma exchange by an indirect immunofluorescence technique on autologous and normal lymphocytes. A reduction in OKT11+ and Leu15+ lymphocytes was observed in all patients before plasmapheresis. Antilymphocyte antibodies were detected in five patients. After plasma exchange, an increase in E-rosette receptor- and Fc receptor-bearing lymphocytes was observed along with a reduction in the amount of antilymphocyte antibodies. PMID- 3084457 TI - Centrifugal elutriation as a method for isolation of large numbers of functionally intact human peripheral blood monocytes. AB - Centrifugal elutriation was used further to isolate human peripheral blood monocytes (HPBM) from mononuclear-enriched cells harvested as a secondary component following platelet concentration collection samples. HPBM were recovered in either one or two populations consisting of either total HPBM or small (SM) and large monocytes (LM). The elutriation was carried out at 3,500 +/- 5 rpm for the separation of lymphocytes and HPBM in Ca++- and Mg++-free PBS without EDTA. An average of 5.05 +/- 1.50 X 10(8) HPBM were recovered in the total HPBM with a purity of 95% +/- 3%. The SM and LM were obtained by splitting the total HPBM into two equal populations with an HPBM purity of 92% +/- 3% and 93% +/- 3, respectively, by nonspecific esterase staining. The elutriation media were shown to have no effect on viability by trypan blue exclusion. All three HPBM populations were shown to be histochemically (lack of reactivity to leu-1 and leu-7) and functionally (depletion of NK cell activity) purified from the lymphocyte population. The HPBM populations were enriched in HLA-Dr, OKM-1, OKM 5, MY-8, and leu M-3 monoclonal antibody marker staining. There were no differences in percent positive cells between SM and LM populations for any of the monocyte-specific monoclonal antibodies. All three monocyte populations mediated antibody-dependent cell-mediated cytotoxicity to human red blood cells, with LM mediating more lysis (27.0% +/- 5%) than SM (7% +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084458 TI - Plasmapheresis: an adjunct to medical management of severe hyperthyroidism. AB - A woman with hyperthyroidism and myasthenia gravis developed respiratory failure in association with radiation-induced thyroiditis. Treatment with steroids, propylthiouracil, propranolol, iodine, and plasmapheresis was associated with dramatic reduction in serum triiodothyronine (T3), serum thyroxine (T4), and thyroglobulin levels and prompt recovery of the patient. The medications that this patient received have been shown to cause an abrupt decline in serum T3 levels with little or no effect on the serum T4 concentration. The 56% decline in serum T4 observed in this patient during the first 24 hours of therapy suggests that plasmapheresis may be a useful adjunct to medical therapy in selected patients with severe hyperthyroidism. PMID- 3084459 TI - Successful preoperative apheresis of factor VIII antibody using factor VIII concentrate as a replacement fluid. AB - Plasma exchange was performed on a patient with hemophilia A and inhibitor to factor VIIIC prior to bilateral cataract removal. Koate was used as replacement fluid with effective reduction of the inhibitor level. From the technical standpoint we found out that factor VIII is best reconstituted in water and directly infused through the venous line and not the centrifuge bowl. PMID- 3084460 TI - Structural studies on teichoic acids in cell walls of several serotypes of Listeria monocytogenes. AB - Structural studies were carried out on the teichoic acids in cell walls of Listeria monocytogenes serotypes 3a, 4b, 4f, 6, and 7. The structure of the dephosphorylated repeating units, obtained by treatment with 46% hydrogen fluoride or alkaline hydrolysis, was examined by methylation analysis, acetolysis, and 1H-NMR spectroscopy. The results of Smith degradation of the teichoic acids and 13C-NMR spectroscopy led to the following most likely structures of the repeating units of the teichoic acids:----1-[N acetylglucosaminyl(alpha 1----4)]ribitol-5-phosphate----for serotype 3a,----4 [galactosyl(alpha 1----6)][glucosyl(beta 1----3)]N -acetylglucosaminyl(beta 1--- 2)ribitol-5-phosphate----for serotype 4b,----4-[galactosyl(alpha 1----6)][N acetylglucosaminyl(alpha 1----3)]N-acetylglucosaminyl(beta 1----2)ribitol -5 phosphate----for serotype 4f,----4-N-acetylglucosaminyl(beta 1----4)ribitol -5 phosphate----for serotype 6, and----1-ribitol-5-phosphate----for serotype 7. About 40% of the repeating units of the teichoic acid from serotype 4f were not substituted at C-3 of beta-N-acetylglucosaminyl residues. PMID- 3084461 TI - A novel FAD-protein that allows effective reduction of methyl viologen by NADH (NADH-methyl viologen reductase) from photosynthetic bacterium, Rhodospirillum rubrum: purification and characterization. AB - It was found that the cytoplasm of light-grown cells of Rhodospirillum rubrum could catalyze the reduction of methyl viologen (MV) (Em, 7 = -0.44 V) by NADH and NADPH. In the present study, the enzyme capable of catalyzing MV reduction by NADH (NADH-MV reductase) was purified 1,500-fold from an extract of cells with a yield of 4.4%. The purification procedure comprised (NH4)2SO4 fractionation, and chromatographies on Sepharose CL-6B, DEAE-Sepharose CL-6B, phenyl-Sepharose CL 4B, Blue-Cellulofine, and TSK-Gel G3000SW. Two NADPH-MV reductases were separated during the purification. The NADH-MV reductase obtained was nearly homogeneous, as judged on polyacrylamide gel electrophoresis both in the presence and absence of sodium dodecyl sulfate. The enzyme has a molecular weight of 220,000 and an isoelectric point of 4.8; it is composed of four subunits with a molecular weight of 57,000, and is bound with about 1 mol FAD/mol subunit. The activity is optimum at pH 8. The Km values for NADH and MV are 115 microM and 1.3 mM, respectively, with a molecular activity of 13,000 min-1. The activity was stimulated 2.4-fold in the presence of 20-100 mM ammonium ions. The enzyme also catalyzed the reduction of benzyl viologen, methylene blue and 2,6-dichlorophenol-indophenol (Em, 7 = -0.36, +0.011, and +0.217 V, respectively) at comparable rates. The ratios of the activity with NADH to that with NADPH were 80, 133, 41, and 5.5 with MV, benzyl viologen, methylene blue and 2,6-dichlorophenolindophenol, respectively. The enzyme was significantly stable in the presence of both 5mM 2 mercaptoethanol and 20% (w/v) glycerol. The activity was not appreciably influenced by the presence of 2 M urea, although the reagent caused dissociation to the subunits. PMID- 3084462 TI - Acid beta-galactosidase from human fibroblasts. A microscale purification method monitored by a highly sensitive enzyme assay. AB - A highly sensitive microassay method and a microscale purification system were developed to isolate the residual acid beta-galactosidase in GM1-gangliosidosis fibroblasts. The sensitivity of the microassay system, composed of a 96-well microplate and a microplate fluorometer, was 100-fold higher than that of the conventional system and the response was linear in the pmole range. Acid beta galactosidase was characterized as a thiol enzyme which was inactivated by a mercuric compound. This enzyme was completely adsorbed on an Hg-agarose column and was easily eluted from the column by 10 mM 2-mercaptoethanol. The microscale purification system using Con A-Sepharose, PAT-Sepharose, and Hg-agarose column chromatography achieved 565- and 7,970-fold purifications of acid beta galactosidase with an overall yields of 44% and 45% from normal and GM1 gangliosidosis fibroblasts, respectively. The purified enzyme fractions did not contain any other lysosomal enzyme activities except for a small amount of beta-N acetylhexosaminidase activity. PMID- 3084463 TI - Antigenicity, catalytic activity and conformation of Agaricus bisporus tyrosinase: interaction of conformation-directed antibodies with the native and irradiated enzyme. AB - The antiferromagnetically spin-coupled Cu2+ pair present in the active center of tyrosinase was found to be indispensable for its catalytic function. However, the metal ion did not contribute to the conformational integrity or antigenicity of the enzyme molecule. Irradiation of tyrosinase with 254 nm light resulted in dose dependent, essentially irreversible losses of its catalytic and antigenic functions. The apparent first order rate constants for the two processes were 17.6 X 10(-2) min-1 and 28.1 X 10(-2) min-1, respectively. The approximately 1.6 fold difference between the two rate constants suggests that the sites of antigenic determinants in tyrosinase are distinguishable from the enzymic active site by their higher photosensitivity. Kinetic analysis of the data as to photoinactivation, and the UV induced losses of antigenicity and structural integrity revealed that UV radiation disrupts the short-range noncovalent interactions occurring within the enzyme molecule. The disruption of the noncovalent interactions results in partial unfolding of the tyrosinase structure which in turn leads to the progressive loss of its catalytic activity and antigenicity. The anti-tyrosinase antibodies raised in rabbits were found to be directed against the native conformation of the enzyme. It is speculated that these antibodies might be useful in exploring the tyrosinase conformation and in studying the effects of various factors on the enzyme surface and molecular structure. PMID- 3084464 TI - Characterization of microsomal NADPH-dependent aldehyde reductase from rat brain. AB - An NADPH-dependent aldehyde reductase was purified from rat brain microsomes to electrophoretic homogeneity. The purified enzyme had a molecular weight of 75,000 and reduced long chain fatty aldehydes such as octanal and hexadecanal with higher affinity (Km values of 0.21 mM and 0.03 mM, respectively) than for various artificial carbonyl compounds such as p-nitrobenzaldehyde and p-nitroacetophenone (Km values of 0.31 mM and 1.4 mM, respectively). The purified microsomal aldehyde reductase also showed NADPH-cytochrome c reductase activity, and it could not be distinguished from NADPH-cytochrome c reductase in molecular weight (75,000), chromatographic behavior, electrophoretic mobility, or immunological properties. The solubilized microsomal fraction treated with steapsin lost the reductase activity for hexadecanal but not that for cytochrome c. These results suggest that the aldehyde reductase in brain microsomes is identical to NADPH-cytochrome c reductase and that a hydrophobic portion of the NADPH-cytochrome c reductase is required for the reduction of hexadecanal. PMID- 3084465 TI - On the mechanism of calmodulin-induced inhibition of microtubule assembly in vitro. AB - Binding of calmodulin to microtubule-associated proteins (MAPs) was analyzed by the equilibrium gel filtration method. The apparent dissociation constant (Kd) of calmodulin binding was found to be 2 microM for tau, and 5 microM for MAP2. These Kd values were similar to the Kd previously determined for calmodulin binding to tubulin. The inhibitory effect of increasing concentrations of calmodulin on the kinetics of microtubule assembly from tau and tubulin was not mimicked by decreasing the concentration of tau alone or tubulin alone. These results suggest that calmodulin inhibits microtubule assembly by its binding to both MAPs and tubulin. PMID- 3084466 TI - Induction of rat E and chicken A-I apolipoproteins and mRNAs during optic nerve degeneration. AB - Apolipoprotein synthesis was measured in control optic nerves and optic nerves undergoing Wallerian degeneration. After short term organ culture with radiolabeled amino acid, optic nerve extracts were reacted with antiserum to rat or chicken apolipoproteins. Immunoprecipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the degenerating rat optic nerve, apo-E synthesis increased from 0.30 to 0.90% of newly synthesized protein and from 0.45 to 1.4% of secreted protein. A DNA-excess solution hybridization assay was constructed to measure the absolute amount of apo-E mRNA in control and degenerating optic nerves. Paralleling the increase in apo-E protein synthesis, the absolute amount of apo-E mRNA was elevated 3- to 4-fold after enucleation. Similar to rat apo-E, apo-A-I synthesis was increased in degenerating chicken optic nerve. Chicken apo-A-I represented 0.65 and 3.5% of newly synthesized protein from control and enucleated optic nerves, respectively. Apo-A-I increased from 0.85 to 5.5% of secreted protein following enucleation. Using in vitro translation to quantitate relative amounts of chicken apo-A-I mRNA, enucleated optic nerve apo-A-I mRNA content was increased 5-fold. These results suggest that local apolipoprotein synthesis may be involved in the mobilization of myelin cholesterol which occurs during Wallerian degeneration. The similar response of the rat and chicken to increase optic nerve apolipoprotein synthesis during degeneration supports the idea that avian peripheral apo-A-I and mammalian peripheral apo-E may be performing functions common to both classes of animals. PMID- 3084467 TI - Urinary endo-beta-galactosidase capable of depolymerizing polylactosaminoglycans. AB - Human urine was found to contain an endo-beta-galactosidase capable of depolymerizing sulfated and non-sulfated polylactosaminoglycans. Using 0.05 M sodium phosphate buffer, pH 7.0, this enzyme was not retained by DEAE-Sephadex A 50 or concanavalin A-Sepharose. The urinary endo-beta-galactosidase liberated a disaccharide with chromatographic mobility identical to 6-O-sulfo-GlcNAc beta 1-- -3Gal as one of the major products from keratan sulfates isolated from whale nasal cartilage, bovine cornea, and human costal cartilage. It also liberated GlcNAc beta 1----3 Gal as one of the major oligosaccharides from erythroglycan. The oligosaccharide profiles produced from various keratan sulfates and erythroglycan by the action of urinary endo-beta-galactosidase are quite similar to those produced by Escherichia freundii endo-beta-galactosidase (Nakagawa, H., Yamada, T., Chien, J.-L., Gardas, A., Kitamikado, M., Li, S.-C., and Li, Y.-T. (1980) J. Biol. Chem. 255, 5955-5959). The presence of urinary endo-beta galactosidase indicates the existence of a new catabolic pathway for polylactosaminoglycans. This pathway involves the cleavage of internal beta galactosyl linkages of the glycan chain. PMID- 3084468 TI - Effect of interleukin-1 on intracellular concentration of sodium, calcium, and potassium in 70Z/3 cells. AB - The cytokine interleukin-1 (IL-1) has been shown to induce the differentiation of a murine pre-B like cell line 70Z/3. An early intracellular event caused by exposure to IL-1 is an amiloride-sensitive progressive rise in the total concentration of intracellular sodium ([Na]i), caused by influx of Na+ from outside, and a transient fall in total intracellular calcium. The results suggest that IL-1-induced influx of Na+ into 70Z/3 occurs via stimulation of the Na+/H+ antiport. IL-1-induced differentiation is also blocked by amiloride suggesting that stimulation of Na+/H+ exchange may play a role in IL-1-induced differentiation. PMID- 3084469 TI - GM1-gangliosidosis. Defective recognition site on beta-galactosidase precursor. AB - Cultured fibroblasts from different variants of GM1-gangliosidosis synthesize normal amounts of 88-kDa beta-galactosidase precursor. Yet the amount of the mature 64-kDa form is reduced to 5-15% of normal values. In this communication it is shown that the mutation in the infantile and adult form of GM1-gangliosidosis interferes with the phosphorylation of precursor beta-galactosidase. As a result the precursor is secreted instead of being compartmentalized into the lysosomes and further processed. The impaired phosphorylation might be due to conformational changes of the precursor molecule. PMID- 3084470 TI - Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells. II. Isolation and characterization of phosphatidylserine auxotrophs. AB - Chinese hamster ovary (CHO) cell mutants that required exogenously added phosphatidylserine for cell growth were isolated by using the replica technique with polyester cloth, and three such mutants were characterized. Labeling experiments on intact cells with 32Pi and L-[U-14C]serine revealed that a phosphatidylserine auxotroph, designated as PSA-3, was strikingly defective in phosphatidylserine biosynthesis. When cells were grown for 2 days without phosphatidylserine, the phosphatidylserine content of PSA-3 was about one-third of that of the parent. In extracts of the mutant, the enzymatic activity of the base-exchange reaction of phospholipids with serine producing phosphatidylserine was reduced to 33% of that in the parent; in addition, the activities of base exchange reactions of phospholipids with choline and ethanolamine in the mutant were also reduced to 1 and 45% of those in the parent, respectively. Furthermore, it was demonstrated that the serine-exchange activity in the parent was inhibited approximately 60% when choline was added to the reaction mixture whereas that in the mutant was not significantly affected. From the results presented here, we conclude the following. There are at least two kinds of serine-exchange enzymes in CHO cells; one (serine-exchange enzyme I) can catalyze the base-exchange reactions of phospholipids with serine, choline, and ethanolamine while the other (serine-exchange enzyme II) does not use the choline as a substrate. Serine exchange enzyme I, in which mutant PSA-3 is defective, plays a major role in phosphatidylserine biosynthesis in CHO cells. Serine-exchange enzyme I is essential for the growth of CHO cells. PMID- 3084471 TI - Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells. III. Genetic evidence for utilization of phosphatidylcholine and phosphatidylethanolamine as precursors. AB - In the preceding paper, we reported that Chinese hamster ovary (CHO) cells contain two different serine-exchange enzymes (I and II) which catalyze the base exchange reaction of phospholipid(s) with serine and that a phosphatidylserine requiring mutant (strain PSA-3) of CHO cells is defective in serine-exchange enzyme I and lacks the ability to synthesize phosphatidylserine (Kuge, O., Nishijima, M., and Akamatsu, Y. (1986) J. Biol. Chem. 261, 5790-5794). In this study, we examined precursor phospholipids for phosphatidylserine biosynthesis in CHO cells. When mutant PSA-3 and parent (CHO-K1) cells were cultured with [32P]phosphatidylcholine, phosphatidylserine in the parent accumulated radioactivity while that in the mutant was not labeled significantly. On the contrary, when cultured with [32P]phosphatidylethanolamine, the mutant incorporated the label into phosphatidylserine more efficiently than the parent. Furthermore, we found that mutant PSA-3 grew normally in growth medium supplemented with 30 microM phosphatidylethanolamine as well as phosphatidylserine and that the biosynthesis of phosphatidylserine in the mutant was biosynthesis of phosphatidylserine in the mutant was normal when cells were cultured in the presence of exogenous phosphatidylethanolamine. The simplest interpretation of these findings is that phosphatidylserine in CHO cells is biosynthesized through the following sequential reactions: phosphatidylcholine--- phosphatidylserine----phosphatidylethanolamine--- - phosphatidylserine. The three reactions are catalyzed by serine-exchange enzyme I, phosphatidylserine decarboxylase, and serine-exchange enzyme II, respectively. PMID- 3084472 TI - A di-N-acetylchitobiase activity is involved in the lysosomal catabolism of asparagine-linked glycoproteins in rat liver. AB - A perfused rat liver was used to study the effects of 5-diazo-4-oxo-L-norvaline on lysosomal glycoprotein catabolism. Addition of this compound (1.0 mM) to the perfusate reduced activity of beta-aspartyl-N-acetylglucosylamine amidohydrolase by 99% in 1 h. Treated livers were unable to completely degrade endocytosed N acetyl[14C]glucosamine-labeled asialo-alpha 1-acid glycoprotein as evidenced by a 50% reduction in radiolabeled serum glycoprotein secretion compared to controls. This decreased degradation was matched by a lysosomal accumulation of glycopeptides with the structure: GlcNAc beta(1-4)GlcNAc-Asn. The result suggested the presence of an unrecognized glycosidase in rat liver lysosomes, since this remnant was extended by one more GlcNAc residue than would have been expected after specific inactivation of the amidohydrolase. Such a novel enzyme would therefore catalyze cleavage of the N-acetylglucosamine residue at the reducing end of alpha 1-acid glycoprotein oligosaccharides only following removal of the linking Asn. The activity was then detected in lysosomal extracts by using intact asialo-biantennary oligosaccharides labeled with [3H] galactose or N acetyl[14C]glucosamine residues as a substrate. To prevent simultaneous digestion of the material from its nonreducing end, beta-D-galactosidase in the enzyme extract was first inactivated with the irreversible active site-directed inhibitor, beta-D-galactopyranosylmethyl-p-nitrophenyltriazene. The observed di-N acetylchitobiose cleaving activity worked optimally at pH 3.4 and was uniquely associated with the lysosomal fraction of the liver homogenate. The enzyme also cleaved triantennary chains and di-N-acetylchitobiose, but failed to hydrolyze substrates that had been reduced with NaBH4. The new glycosidase was well separated from N-acetyl-beta-D-glucosaminidase (assayed with p-nitrophenyl-beta-D glucosaminide) by gel filtration chromatography and had an apparent molecular weight of 37,000. A similar enzyme that hydrolyzes di-N-acetylchitobiose had previously been found in extracts of human liver (Stirling, J. L. (1974) FEBS Lett. 39, 171-175). PMID- 3084473 TI - Metabolism of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3 phosphocholine) by human promyelocytic leukemic HL60 cells. Stimulated expression of phospholipase A2 and acetyltransferase requires differentiation. AB - Human promyelocytic leukemia (HL60) cells can be induced to differentiate into mature granulocytes by exposure to dimethyl sulfoxide. The addition of N formylMet-Leu-Phe or the Ca2+ ionophore A23187 to these differentiated cells generated 15-30 pmol of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero 3-phosphocholine (alkylacetyl-GPC)/10(6) cells as quantified by platelet aggregation assays. Under identical conditions, uninduced cells produced little alkylacetyl-GPC. Upon the addition of ionophore A23187, differentiated cells, and not uninduced ones, released [14C]arachidonate from prelabeled phospholipids including ether-linked phosphatidylcholines, formed both 3H-labeled 1-O-alkyl-2 lyso-sn-glycero-3-phosphocholine (alkyllyso-GPC) and [3H]alkylacetyl-GPC from endogenous 3H-labeled 1-O-alkyl-2-(long chain) acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC), and incorporated exogenously added [3H]acetate or [3H]alkyllyso GPC into alkylacetyl-GPC. These results are suggestive that both phospholipase A2 and acetyltransferase activities are involved in alkylacetyl-GPC biosynthesis by HL60 cells and that these activities appear during differentiation. However, when measured in cell extracts, the activities of phospholipase A2 and acetyltransferase of uninduced cells were virtually indistinguishable from those of differentiated cells. Uninduced cells exhibited enhanced incorporation of [3H]alkyllyso-GPC or [3H]alkylacetyl-GPC into alkylacyl-GPC and of [14C]arachidonate and [14C]oleate into various phospholipids including phosphatidylcholine. However, such enhanced expression of acylation reactions could not account for the lack of accumulation of arachidonate or of alkylacetyl GPC by uninduced cells. Furthermore, analyses of phospholipid classes by phosphorus determination showed no significant alterations in phospholipid composition of HL60 cells during differentiation. Together these data are suggestive that mechanisms regulating the activation of phospholipase A2 and acetyltransferase activities are defective in uninduced cells and that an increased concentration of cytosolic free Ca2+ alone is not a sufficient requirement for these mechanisms. PMID- 3084474 TI - Sustained diacylglycerol formation from inositol phospholipids in angiotensin II stimulated vascular smooth muscle cells. AB - Angiotensin II acts on cultured rat aortic vascular smooth muscle cells to stimulate phospholipase C-mediated hydrolysis of membrane phosphoinositides and subsequent formation of diacylglycerol and inositol phosphates. In intact cells, angiotensin II induces a dose-dependent increase in diglyceride which is detectable after 5 s and sustained for at least 20 min. Angiotensin II (100 nM) stimulated diglyceride formation is biphasic, peaking at 15 s (227 +/- 19% control) and at 5 min (303 +/- 23% control). Simultaneous analysis of labeled inositol phospholipids shows that at 15 s phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 4-phosphate (PIP) decline to 52 +/- 6% control and 63 +/- 5% control, respectively, while phosphatidylinositol (PI) remains unchanged. In contrast, at 5 min, PIP2 and PIP have returned toward control levels (92 +/- 2 and 82 +/- 4% control, respectively), while PI has decreased substantially (81 +/- 2% control). The calcium ionophore ionomycin (15 microM) stimulates diglyceride accumulation but does not cause PI hydrolysis. 4 beta Phorbol 12-myristate 13-acetate, an activator of protein kinase C, inhibits early PIP and PIP2 breakdown and diglyceride formation, without inhibiting late-phase diglyceride accumulation. Thus, angiotensin II induces rapid transient breakdown of PIP and PIP2 and delayed hydrolysis of PI. The rapid attenuation of polyphosphoinositide breakdown is likely caused by a protein kinase C-mediated inhibition of PIP and PIP2 hydrolysis. While in vascular smooth muscle stimulated with angiotensin II inositol 1,4,5-trisphosphate formation is transient, diglyceride production is biphasic, suggesting that initial and sustained diglyceride formation from the phosphoinositides results from different biochemical and/or cellular processes. PMID- 3084475 TI - The formation of styrene glutathione adducts catalyzed by prostaglandin H synthase. A possible new mechanism for the formation of glutathione conjugates. AB - The metabolism of styrene by prostaglandin hydroperoxidase and horseradish peroxidase was examined. Ram seminal vesicle microsomes in the presence of arachidonic acid or hydrogen peroxide and glutathione converted styrene to glutathione adducts. Neither styrene 7,8-oxide nor styrene glycol was detected as a product in the incubation. Also, the addition of styrene 7,8-oxide and glutathione to ram seminal vesicle microsomes did not yield styrene glutathione adducts. The peroxidase-generated styrene glutathione adducts were isolated by high pressure liquid chromatography and characterized by NMR and tandem mass spectrometry as a mixture of (2R)- and (2S)-S-(2-phenyl-2 hydroxyethyl)glutathione. (1R)- and (1S)-S-(1-phenyl-2-hydroxyethyl)glutathione were not formed by the peroxidase system. The addition of phenol or aminopyrine to incubations, which greatly enhances the oxidation of glutathione to a thiyl radical by peroxidases, increased the formation of styrene glutathione adducts. We propose a new mechanism for the formation of glutathione adducts that is independent of epoxide formation but dependent on the initial oxidation of glutathione to a thiyl radical by the peroxidase, and the subsequent reaction of the thiyl radical with a suitable substrate, such as styrene. PMID- 3084476 TI - Identification of the type IX collagen polypeptide chains. The alpha 2(IX) polypeptide carries the chondroitin sulfate chain(s). AB - Type IX collagen has recently been shown to contain glycosaminoglycan chain(s) and furthermore to be immunologically identical with proteoglycan Lt (Vaughan, L., Winterhalter, K. H., and Bruckner, P. (1985) J. Biol. Chem. 260, 4758-4763). Here we demonstrate that the chondroitin sulfate carrying 115-kDa polypeptide of type IX collagen corresponds to the alpha 2(IX) chain. In addition the 84- and 68 kDa polypeptides were identified as the alpha 1(IX) and the alpha 3(IX) chains, respectively. This conclusion is based on a comparison of the tryptic fingerprints of the 84-, 115-, and 68-kDa chains of type IX collagen on high performance liquid chromatography with the similarly treated C2, C3, and C5 chains of the peptic fragment HMW. In addition, we provide evidence that both the C3 and C4 components of HMW are derived from the alpha 2(IX) chain. PMID- 3084477 TI - Purification and characterization of a UDP-Gal:beta-D-Gal(1,4)-D-GlcNAc alpha(1,3)-galactosyltransferase from Ehrlich ascites tumor cells. AB - A UDP-Gal:N-acetyllactosaminide alpha (1,3)-galactosyltransferase from Ehrlich ascites tumor cells has been purified over 200,000-fold to apparent electrophoretic homogeneity. The purified enzyme transfers D-galactosyl groups from UDP-Gal to beta-D-Gal-(1,4)-D-GlcNAc in alpha-linkage. The apparent Km values for donor and acceptor substrates are 12.6 microM and 1.15 mM, respectively. The trisaccharides beta-D-Gal(1,4)-beta-D-GlcNAc(1,2)- or (1,6)-D Man exhibit a Km 5-fold lower than that of N-acetyllactosamine, and an even more pronounced effect is observed with the biantennary pentasaccharide beta-D Gal(1,4)-beta-D-GlcNAc(1,2)-[beta-D-Gal(1, 4)-beta-D-GlcNAc-(1,6)]-D-Man (Km 0.10 mM). The transferase shows a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions with an apparent subunit molecular weight of 80,000, exhibits a pH optimum at 6.2, and requires Mn2+ ions and detergent for enzymatic activity. Specificity studies using immobilized oligosaccharides show that the minimum acceptor structure for the alpha galactosyltransferase is N-acetyllactosamine. The narrow specificity of the alpha galactosyltransferase is indicated by the fact that lactose, beta-D-Gal(1,3)-D GlcNAc, and beta-D-Gal(1,4)-[alpha-L-Fuc(1,3)]-D-GlcNAc are very poor acceptors. The enzyme differs from the blood-group B-specified galactosyltransferase in that the sequence alpha-L-Fuc(1,2)-beta-D-Gal(1,4)-D-GlcNAc is not an acceptor. Oligosaccharides, glycoproteins, glycolipids, and glycosaminoglycans containing the terminal nonreducing N-acetyllactosamine unit all serve as acceptors for the enzyme. PMID- 3084478 TI - Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. AB - Microtubule-associated protein tau was purified from bovine brain microtubules by either (1) phosphocellulose chromatography, (2) heat treatment at pH 6.4, (3) heat treatment at pH 2.7, (4) heat treatment at pH 2.7 followed by extraction with perchloric acid and precipitation with glycerol, or (5) by precipitation with ammonium sulfate followed by extraction with perchloric acid. All of these tau preparations reacted specifically with antibodies to Alzheimer paired helical filaments. Affinity purified antibodies to tau labeled both Alzheimer neurofibrillary tangles and plaque neurites but not amyloid in Alzheimer brain tissue sections and labeled paired helical filament polypeptides on Western blots. Human brain tau and paired helical filament polypeptides co-migrated on sodium dodecyl sulfate-polyacrylamide gels. These results suggest that tau is a major component of Alzheimer paired helical filaments. PMID- 3084479 TI - Rat liver UDP-glucuronosyltransferase. Sequence and expression of a cDNA encoding a phenobarbital-inducible form. AB - The cDNA encoding a phenobarbital-inducible form of rat liver UDP glucuronosyltransferase has been isolated, sequenced, and expressed to yield a catalytically active enzyme. The cDNA was found to be 1,961 nucleotides in length and to have an open reading frame of 1,590 nucleotides flanked by 25 and 346 base pairs of 5' and 3' untranslated regions, respectively. The open reading frame encodes a protein of 529 residues (Mr = 60,484) and contains amino-terminal and carboxy-terminal segments characteristic of a signal peptide and a transmembrane anchoring region, respectively. Two potential asparagine-linked glycosylation sites are located between these segments. In an in vitro transcription translation reaction, the cDNA directed the synthesis of a 52,000-dalton polypeptide with immunologic epitopes characteristic of native microsomal UDP glucuronosyltransferase. This in vitro synthesized polypeptide was cleaved and glycosylated when dog pancreatic microsomes were included in the in vitro reaction. The coding region of the cDNA was inserted into a SV40 recombinant vector, and this construct transfected into permissive monkey kidney cells. Seventy hours after transfection, the glucuronidation of 4-methylumbelliferone was detected in lysates of cells containing the cDNA in the correct orientation with respect to SV40 transcription signals. This experimental approach should allow definitive characterization of the structure, function, and heterogeneity of this major family of drug-metabolizing enzymes. PMID- 3084480 TI - Temperature sensitivity and substrate specificity of two distinct Na+-activated D glucose transport systems in guinea pig jejunal brush border membrane vesicles. AB - D-Glucose transport was studied with isolated brush border membrane vesicles from guinea pig jejunum. Saturation curves were carried out at either 25 or 35 degrees C in buffers containing Na+, Li+, K+ (100 mM chloride salt), or sorbitol (200 mM). Uncorrected uptake rates were fitted by nonlinear regression analysis to an equation involving one diffusional and two saturable terms. In the presence of Na+ at 35 degrees C, two saturable systems (Km = 0.4 and 24 mM, respectively) were evident, as well as a diffusion component quantitatively identical with that measured with L-glucose in separate experiments. In contrast, at 25 degrees C only one saturable system was apparent (Km = 1.2 mM): the second exhibited diffusion-like kinetics. In the presence of Na+ at 35 degrees C, D-glucose uptake was fully inhibited by both D-glucose and D-galactose, whereas alpha methylglucoside gave kinetics of partial inhibition. We conclude that in the presence of Na+ there are at least two distinct D-glucose transport systems: 1) System I, a low temperature-sensitive system, fully inhibited by D-glucose, D galactose, and alpha-methylglucoside; we identify it as the "classical" D glucose/Na+ cotransport system, insensitive to inhibition by cytochalasin B and obligatorily dependent on Na+; and 2) System II, a high temperature-sensitive system where D-glucose and D-galactose inhibit but alpha-methylglucoside is inert. Its cation specificity is unclear but it appears to be sensitive to cytochalasin B inhibition. When Li+ or K+ substituted for Na+, only one transport system was apparent. The Li+-activated transport was: independent of the incubation temperature; inhibited by D-glucose and D-galactose but not by alpha methylglucoside, 2-deoxy-D-glucose, D-mannose, and D-xylose; and sensitive to cytochalasin B inhibition. The exact nature of the system (or systems) involved in D-glucose transport in the absence of sodium remains to be established. PMID- 3084481 TI - Terbium probe of calcium-binding sites on the prothrombin-membrane complex. AB - Terbium was used as a probe of Ca2+-binding sites on the prothrombin-phospholipid complex. Stoichiometric titrations of prothrombin binding to phospholipid vesicles with either Tb3+ or Ca2+ showed that a minimum of 8 metal ions were needed for binding prothrombin to vesicles (3 Mn2+ + 5 Ca2+ for prothrombin or 8 Tb3+ for F-1). When Ca2+ alone was used, a total of about 11 metal ions were needed for complete binding. These stoichiometries indicated 3 classes of metal ions: one class needed to induce the conformational change, a second required for protein-membrane contact, and a third class bound at other sites on the protein that are not involved in membrane binding. By adding Tb3+ to solutions containing both protein and phospholipid, undesirable Tb3+-induced events, such as irreversible aggregation of prothrombin or vesicle fusion, were avoided. Protein vesicle binding apparently prevented protein aggregation or vesicle fusion. The protein-vesicle binding affinity was severalfold greater in the presence of Tb3+ compared to Ca2+. CoEDTA quenching of Tb3+ bound to the prothrombin-phospholipid complexes indicated that all metal ions were at least partially exposed to the quencher. Some populations of Tb3+ showed lower quenching constants when all of the prothrombin was bound. Tb3+ emission lifetimes revealed that some Tb3+ ions in the protein-membrane complex were in a different environment from those bound to the protein alone. The results indicated that the metal ions in the prothrombin-membrane complex are relatively open to the solvent yet do affect the characteristics of the protein-membrane binding equilibrium. PMID- 3084482 TI - Matrix magnesium and the permeability of heart mitochondria to potassium ion. AB - Isolated beef heart mitochondria were treated with A23187 in the presence of different concentrations of Mg2+ or EDTA to establish varying levels of total mitochondrial Mg2+. The Mg2+ content was related to the rate of passive swelling of the mitochondria in potassium acetate and other potassium salts in which swelling is presumed to depend on K+ entry via an endogenous K+/H+ antiport. Swelling in these salts does not commence until Mg2+ has been depleted from an initial value of 36 nmol X mg-1 of protein to 8 nmol/mg-1, or less. Below this level, swelling increases linearly with decreasing Mg2+ to a maximum rate at 2 nmol of Mg2+ X mg-1. Rotenone-treated heart mitochondria suspended in 75 mM potassium acetate at pH 7.80 show no delta pH by 5,5-dimethyl-2,4 oxazolidinedione distribution. Distribution of methylamine also shows essentially no delta pH under these conditions when allowance is made for binding of [14C]methylamine by mitochondrial membranes under these conditions. Addition of A23187 results in a small and transient delta pH (delta pH less than 0.14, acid interior) as measured by methylamine distribution. Estimation of the maximum matrix free Mg2+ concentration from the maximum delta pH observed and the external free Mg2+ concentration at equilibrium with A23187 shows that swelling is not initiated until matrix free Mg2+ is decreased to below 150 microM. An independent estimate of free Mg2+ using a null-point procedure gives a lower, but quite similar value (50 microM) for maximum matrix free Mg2+ when swelling commences. The large depletion of total and free Mg2+ that is required to activate swelling in potassium acetate (and presumably K+/H+ antiport activity) does not appear to be compatible with previous indications that free Mg2+ acts as a "carrier brake" to regulate K+ extrusion from the mitochondrion on such an antiport (Garlid, K. D. (1980) J. Biol. Chem. 255, 11273-11279). The removal of a tightly bound component of mitochondrial Mg2+ is closely related to increased K+ permeability and increased passive swelling in potassium salts. This Mg2+ appears to play a role in the maintenance of mitochondrial membrane structure and integrity. PMID- 3084483 TI - Functional interaction of purified muscarinic receptors with purified inhibitory guanine nucleotide regulatory proteins reconstituted in phospholipid vesicles. AB - The GTP binding regulatory protein (Ni involved in adenylate cyclase inhibition was purified from rat brain and reconstituted, together with muscarinic cholinergic receptors purified from porcine brain, into phospholipid vesicles. Guanosine 5'-O-(3-[35S]thio)-triphosphate ([35S]GTP gamma S) binding and GTP hydrolyzing activities of reconstituted Ni were stimulated by the addition of a muscarinic agonist, carbachol. The effect of carbachol was to increase the Vmax values of these activities, but the Km values were also increased slightly in most cases. Carbachol bound to vesicles with the same order of magnitude of Km as that for stimulation of GTPase. The affinity of this binding was reduced by GTP gamma S, indicating that the high-affinity receptor-Ni complex was formed in a GTP-dependent manner in reconstituted vesicles. Incubation of Ni with NAD and islet-activating protein (IAP), pertussis toxin, caused ADP-ribosylation of the alpha-subunit of Ni. The criteria for the receptor-Ni interaction, i.e. carbachol stimulation of the activities of Ni and the GTP gamma S effect on carbachol binding, were no longer observed, when this IAP-treated Ni, instead of the nontreated Ni, was reconstituted into vesicles, though there was no difference between IAP-treated and nontreated Ni in their basal activities observable without carbachol. No, the protein with a character very similar to Ni in rat brain, was also coupled to muscarinic receptors when they were reconstituted into vesicles under the same conditions. Thus, GTP-binding proteins serving as the substrate of IAP-catalyzed ADP-ribosylation are capable of interaction functionally with muscarinic receptors in phospholipid vesicles. PMID- 3084485 TI - Cadaverine covalently linked to a peptidoglycan is an essential constituent of the peptidoglycan necessary for the normal growth in Selenomonas ruminantium. AB - Cadaverine links covalently to the D-glutamic acid residue of the peptidoglycan in Selenomonas ruminantium, a strictly anaerobic Gram-negative bacterium (Kamio, Y., Itoh, Y., and Terawaki, Y. (1981) J. Bacteriol. 146, 49-53). This report clarifies a physiological function of cadaverine in this organism by using DL alpha-difluoromethyllysine, which had previously been shown to be a selective irreversible inhibitor of lysine decarboxylase of Mycoplasma dispar (Poso, H., MaCann, P.P., Tanskanen, R., Bey, P., and Sjoerdsma, A. (1984) Biochem. Biophys. Res. Commun. 125, 205-210). DL-alpha-Difluoromethyllysine is now shown to be a potent and irreversible inhibitor of lysine decarboxylase of S. ruminantium in vitro; however, it did not inhibit the transfer of cadaverine to the alpha carboxyl group of the D-glutamic acid residue of the peptidoglycan. DL-alpha Difluoromethyllysine at 5 mM markedly inhibited the growth of the bacterium and caused rapid cell lysis. Immediately before the cell lysis, almost all cells became swollen, and such cells showed a loosened envelope structure when studied by electron microscopy. The peptidoglycan prepared from the DL-alpha difluoromethyllysine-treated cells did not have covalently linked cadaverine. The growth inhibition by DL-alpha-difluoromethyllysine was completely reversed by adding cadaverine (1 mM) to the medium. Furthermore, the exogenous cadaverine was exclusively incorporated into the peptidoglycan in the presence of DL-alpha difluoromethyllysine (5 mM), and a normal peptidoglycan was synthesized. The cell lysis and the formation of an abnormal cell structure were completely prevented by cadaverine added to the medium. We conclude that cadaverine covalently linked to the peptidoglycan in S. ruminantium is an essential constituent of the peptidoglycan and is required for cell surface integrity and the normal growth of S. ruminantium. PMID- 3084484 TI - Incorporation of beta-fluoroasparagine into peptides prevents N-linked glycosylation. In vitro studies with synthetic fluoropeptides. AB - Previously, we reported that incorporation of threo-beta-fluoroasparagine into cellular protein inhibits N-linked glycosylation. We now show that short synthetic peptides which contain N-acetyl-threo-beta-fluoroasparagine fail to undergo glycosylation in a cell-free system except at extremely high substrate concentrations. An N-benzoyl-threo-beta-fluoroasparagine-containing peptide has a 100-fold lower Vmax/Km than the analogous N-benzoyl-asparagine-containing peptide. Substitution of a fluorine for a hydrogen on the beta-carbon of asparagine weakens the ability of the peptide to bind the oligosaccharyltransferase. A 100-fold excess of acetyl-threo-beta fluoroasparaginyl-leucyl-threonine methylamide over acetyl-asparaginyl-leucyl threonine methylamide inhibited glycosylation of the latter peptide by less than 10%. Both threo-beta-fluoroasparagine and erythro-beta-fluoroasparagine containing peptides are glycosylated at the same rate. Glycofluoropeptides generated from beta-fluoroasparagine-containing peptides were N-glycosylated. These cell-free studies with synthetic fluoropeptides suggest that incorporation of beta-fluoroasparagine into cellular protein inhibits N-linked glycosylation by rendering protein substrates ineffective for glycosylation. In the course of this work, we also demonstrate that the N-linked glycosylating enzyme acts only on L asparagine-containing peptides and not on D-asparagine peptides. PMID- 3084486 TI - The neural type II regulatory subunit of cAMP-dependent protein kinase is present and regulated by hormones in the rat ovary. AB - In this study purified isoforms of rat ovarian regulatory subunit of type II cAMP dependent protein kinase (R-II) were compared with R-II purified from rat brain. A special neural form of R-II has been previously described in bovine brain. Analysis by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved three isoforms of rat ovarian R-II (R-II54, Mr = 54,000; R-II52, Mr = 52,000; and R-II51, Mr = 51,000) compared to two R-II isoforms in rat brain (R-II54 and R-II52). Polychromatic silver-stained peptide maps of purified R-II subunits indicated that peptides generated from both rat ovarian R II52 and R-II51 were similar (if not identical) to the peptides of the neural form, R-II52, purified from rat brain. These peptides differed markedly from those generated from R-II54 of either rat ovary, brain, or heart. Ovarian R II52/51 photoaffinity labeled with 8-N3-[32P]cAMP and analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis was shown to consist of three (rather than two) isoelectric variants, which were similar to three variants resolved from rat brain R-II and clearly distinct from that of rat heart R-II54. An antibody which recognized both the R-II54 and R-II52/51 isoforms of rat ovarian extracts also recognized both forms of rat brain R-II (R-II54 and R II52) and similar forms in extracts of rat adrenal and parotid glands. These results strongly suggest that the R-II52 isoform previously designated as a neural specific form of R-II is present in high concentrations in a nonneural tissue, the rat ovary. PMID- 3084487 TI - Biosynthesis of proteoglycans by rat embryo parietal yolk sacs in organ culture. AB - The embryonic rat parietal yolk sac has been previously shown to synthesize a number of basement membrane glycoconjugates including type IV procollagen, laminin, and entactin. In this study, parietal yolk sacs were isolated from 14.5 day rat embryos and incubated in organ culture for 4-7 h with [35S]sulfate, [3H] glucosamine, and/or 3H-labeled amino acids, and the newly synthesized proteoglycans were characterized. The major [35S]sulfate-labeled macromolecule represented approximately 90% of the medium and 80% of the tissue radioactivity. It also represented nearly 80% of the total [3H]glucosamine-labeled glycosaminoglycans. After purification by sequential ion-exchange chromatography and isopycnic CsCI density gradient ultracentrifugation, size-exclusion high performance liquid chromatography showed a single species with an estimated Mr of 8-9 X 10(5). The intact proteoglycan did not form aggregates in the presence of exogenous hyaluronic acid or cartilage aggregates. Alkaline borohydride treatment released glycosaminoglycan chains with Mr of 2.0 X 10(4) which were susceptible to chondroitinase AC II and chondroitinase ABC digestion. Analysis by high performance liquid chromatography of the disaccharides generated by chondroitinase ABC digestion revealed that chondroitin 6-sulfate was the predominant isomer. The uronic acid content of the glycosaminoglycans was 92% glucuronic acid and 8% iduronic acid, and the hexosamine content was 96% galactosamine and 4% glucosamine. No significant amounts of N- or O-linked oligosaccharides were detected. Deglycosylation of the proteoglycan with chondroitinase ABC in the presence of protease inhibitors revealed a protein core with an estimated Mr of 1.25-1.35 X 10(5). These results indicated that the major proteoglycan synthesized by the 14.5-day rat embryo parietal yolk sac is a high density chondroitin sulfate containing small amounts of copolymeric dermatan sulfate. Hyaluronic acid and minor amounts of heparan sulfate proteoglycan were also detected. PMID- 3084488 TI - Calcium-dependent oxidation of 5,8,11-icosatrienoic acid by the cyclooxygenase enzyme system. AB - Mead (5,8,11-icosatrienoic) acid was found to be metabolized by the cyclooxygenase enzyme system of ram seminal vesicle microsomes in a calcium dependent manner. Although the enzyme converted Mead acid to products more slowly and less completely than the isomeric 8,11,14-icosatrienoic acid, both oxidations were inhibitable by indomethacin. Experiments using purified cyclooxygenase confirmed the participation of this enzyme system in the calcium-dependent oxidation. The products of the oxidation were separated by high performance liquid chromatography and analyzed by ultraviolet and gas chromatography-mass spectrometry. The spectra obtained were consistent with the products having the structures 13-hydroxy-5,8,11-icosatrienoate (the major product), 11-hydroxy 5,8,12-icosatrienoate, 9-hydroxy-5,7,11-icosatrienoate, and two isomeric 8,11 dihydroxy-5,9,12-icosatrienoates. No prostaglandin-like, cyclized products could be identified. This report is only the second to illustrate a calcium-dependent oxidation of a polyunsaturated fatty acid by a cyclooxygenase enzyme system and further extends the metabolic potential of Mead acid. PMID- 3084489 TI - Phycobiliprotein-bilin linkage diversity. I. Structural studies on A- and D-ring linked phycocyanobilins. AB - Phycocyanobilin (PCB) peptides alpha-1 PCB and beta-2T PCB were obtained by proteolytic degradation of Synechococcus 6301 C-phycocyanin. These peptides were found to have the following sequences. alpha-1 PCB Cys(PCB)-Ala-Arg beta-2T PCB Ile-Thr-Gln-Gly-Asp-Cys(PCB)-Ser-Ala. The peptides were examined by 1H NMR, circular dichroism spectroscopy, and secondary ion mass spectrometry. The 1H NMR data confirmed that in each case the bilin was attached through a single linkage, a thioether bond between the cysteinyl residue and the tetrapyrrole moiety. Comparison of the 1H NMR spectra of these peptides with those of appropriate model compounds showed that the thioether linkage in alpha-1 PCB was to the C-3' position and that in beta-2T PCB to the C-18' position on the bilin. Refluxing in neutral methanol under nitrogen led to the release of PCB from alpha-1 PCB but did not release the D-ring-linked tetrapyrrole from beta-2T. The above results together with those of an earlier study (Lagarias, J. C., Glazer, A. N., and Rapoport, H. (1979) J. Am. Chem. Soc. 101, 5030-5037) complete the determination of the mode of linkage of each of the three bilins on C-phycocyanin; two are linked through ring A and one through ring D. This is the first documented report of a singly D-ring-linked bilin. PMID- 3084490 TI - Interaction of thrombospondin with resting and stimulated human platelets. AB - The interaction of isolated and radioiodinated thrombospondin with washed human platelets has been characterized. The ligand bound to nonstimulated and thrombin stimulated platelets in a time-dependent manner, and apparent steady state was reached within 25 min. Binding was not due to iodination of the ligand and was inhibited by nonlabeled thrombospondin but not by unrelated proteins, and bound ligand was identical with thrombospondin in terms of subunit structure. Nonlinear curve-fitting analyses of binding to resting platelets suggested the presence of a single class of sites which bound 3,100 +/- 1,000 molecules/platelet with an apparent Kd of 50 +/- 20 nM. This interaction was not attributable to contaminating cells or inadvertant platelet activation. Binding to thrombin stimulated platelets had a lower apparent affinity (Kd = 250 +/- 100 nM) and higher apparent capacity (35,600 +/- 9,600 molecules/platelet). Thrombin-enhanced binding was dependent upon agonist dose and platelet stimulation. Fibrinogen, a monoclonal antibody to GPIIb-IIIa, temperature, and divalent ions had differential effects upon thrombospondin binding to resting and stimulated platelets, suggesting the presence of two distinct mechanisms of thrombospondin binding to platelets. While thrombospondin binding to thrombin-stimulated platelets occurs with characteristics similar to those observed for fibrinogen, fibronectin, and von Willebrand Factor, its high affinity interaction with resting platelets is unique to this adhesive glycoprotein. PMID- 3084491 TI - Purification of DNA ligase II from calf thymus and preparation of rabbit antibody against calf thymus DNA ligase II. AB - DNA ligase II has been purified about 4,000-fold to apparent homogeneity from a calf thymus extract. The ligase consists of a single polypeptide with a molecular weight of 68,000 as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. On fluorography after electrophoresis, a DNA ligase-[3H]AMP complex gave a single band corresponding to a molecular weight of 68,000. The Km values of the ligase for ATP and nicked DNA (5'-phosphoryl ends) were obtained to be 40 and 0.04 microM, respectively. Antibody against calf thymus DNA ligase II was prepared by injecting the purified enzyme into a rabbit. The antibody cross reacted with DNA ligase II but not with calf thymus DNA ligase I. DNA ligase II was not affected by antibody against calf thymus DNA ligase I with a molecular weight of 130,000 (Teraoka, H. and Tsukada, K. (1982) J. Biol. Chem. 257, 4758 4763). These results indicate that DNA ligase II (Mr = 68,000) is immunologically distinct from DNA ligase I (Mr = 130,000). PMID- 3084492 TI - Interaction of the cytoskeletal component vinculin with bilayer structures analyzed with a photoactivatable phospholipid. AB - The cytoskeletal component vinculin has been proposed to act as an actin-plasma membrane linker. In order to demonstrate a possible direct interaction of vinculin with bilayers, photolabeling with a phospholipid generating a highly reactive carbene was used. This phosphatidylcholine analogue (1-palmitoyl-2-[10 [4-[(trifluoromethyl)diazirinyl]phenyl]-[3H] 9-oxaundecanoyl]-sn-glycero-3 phosphocholine), with the photoactivatable diazirine group on its apolar portion, has been shown to label selectively membrane-embedded domains of membrane proteins. Vinculin is significantly labeled upon incubation and photolysis with liposomes containing trace amounts of this photoactivatable phospholipid, but only when the liposomes also contain acidic phospholipids. Labeling of vinculin is markedly increased (5-17-fold) by all acidic phospholipids tested so far (30%, w/w), compared to labeling in neutral phospholipids. Labeling is high at low ionic strength, but significant vinculin labeling can still be observed at physiological salt concentrations and acidic phospholipid content of the membrane. Our results provide evidence that vinculin inserts into the hydrophobic part of the bilayer by interacting with acidic phospholipids. A similar interaction may be of importance in vivo. PMID- 3084493 TI - Modulation of chromatin superstructure induced by poly(ADP-ribose) synthesis and degradation. AB - It has been demonstrated recently by Poirier et al. (Poirier, G. G., de Murcia, G., Jongstra-Bilen, J., Niedergang, C., and Mandel, P. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 3423-3427) that poly(ADP-ribosyl)ation of pancreatic nucleosomes causes relaxation of the chromatin superstructure through H1 modification. The in vitro effect of poly(ADP-ribose) synthesis and degradation on calf thymus chromatin was investigated by the time course incorporation of ADP-ribose, electron microscopy, analytical ultracentrifugation, and autoradiography of the protein acceptors. Purified calf thymus poly(ADP-ribose) polymerase and partially purified bull testis poly(ADP-ribose) glycohydrolase were used. Degradation of ADP-ribose units on hyper(ADP-ribosyl)ated H1 by poly(ADP-ribose) glycohydrolase restores the native condensed chromatin superstructure. This reversible conformational change induced by poly(ADP-ribosyl)ation on nucleosomal arrangement could be one of the mechanisms by which the accessibility of DNA polymerases and/or excision-repair enzymes is favored, the native structure being fully restorable. PMID- 3084494 TI - Purification of the major GTP-binding proteins from human placental membranes. AB - Using minor modifications of procedures developed to purify GTP-binding proteins (G-proteins) from rabbit liver, we have purified the major G-proteins present in human placental membranes. One, referred to as Gi, is the major substrate for pertussis toxin-catalyzed ADP-ribosylation and has an alpha-subunit of 41,000 daltons, and beta-subunit of 36,000 and 35,000 daltons, and a gamma-subunit of 10,000 daltons. The other protein, referred to as Gp, was identified by its ability to bind guanine nucleotides specifically with high affinity. This activity was resolved from Gs and Gi by the second step of purification (AcA-34 chromatography) and was further purified through heptylamine-Sepharose and hydroxylapatite. The guanine nucleotide-binding site, which can be resolved by high performance liquid chromatography procedures and identified by a photolyzable GTP analogue, is associated with a 21,000-dalton protein (Gp alpha) that copurifies with beta gamma-subunits indistinguishable from the beta gamma subunits associated with Gs and Gi. This protein represents a potentially novel member of the structurally and functionally homologous family of G-proteins that are transducing elements in the receptor-mediated regulation of a variety of cellular processes. PMID- 3084495 TI - Carcinogenic effect of cisplatin (cis-diammine-dichloroplatinum (II), CDDP) in BD IX rats. AB - The potent antitumor agent cis-diammine-dichloroplatinum(II) (CDDP) also has carcinogenic properties. CDDP was administered i.p. to 50 BD IX rats for 3 weeks, 3 X 1 mg/kg body weight per week. All animals were pretreated by hydration before each CDDP application, but only half the animals additionally received mannitol together with the CDDP solution, as a nephroprotective measure. To date, 455 days after the first application, 33 animals have died, 13 of them of malignancies: 12 leukemias and 1 renal fibrosarcoma. So far, no significant differences in the frequency and type of malignancies have been observed between animals which additionally received mannitol and the others which did not. In the control group of 25 animals, which received NaCl solution 0.9% i.p. (3 X 1 ml/kg per week, for 3 weeks) malignancies have not yet occurred. The high tumor incidence determined in this study reveals that the risk of secondary tumor development in patients treated with CDDP should not be disregarded. PMID- 3084496 TI - Patterns of destruction of mouse neuroblastoma cells by extracellular hydrogen peroxide formed by 6-hydroxydopamine and ascorbate. AB - The patterns of the cytolytic effects of 6-hydroxydopamine (6-OHDA), with/without ascorbate, on C-1300 and three other cloned mouse neuroblastoma cell lines (N1E 115, NS-20, N-18) were studied in vitro. The sensitivity to 6-OHDA differed and the three cloned cell lines were more sensitive than the wild type C-1300 cell line. Ascorbate synergistically potentiated the cytolytic effect of 6-OHDA to all four cell lines. The 6-OHDA cytotoxicity was eliminated by the addition of exogenous catalase but not by addition of other oxygen free radical scavengers, thereby suggesting that the hydrogen peroxide formed might influence the cells, extracellularly. In addition, the critical time for tumor cell lysis was the first 60 min of the reaction. The cytotoxicity induced by the unmasked cyclophosphamide, 4-hydroperoxycyclophosphamide, was synergistically enhanced in the presence of a nontoxic concentration of 6-OHDA and ascorbate. These data suggest that reactive oxygen intermediates may prove to be a good tool for destroying neuroblastoma cells. PMID- 3084498 TI - In situ hybridization at the electron microscope level: localization of transcripts on ultrathin sections of Lowicryl K4M-embedded tissue using biotinylated probes and protein A-gold complexes. AB - A technique has been developed for localizing hybrids formed in situ on semi-thin and ultrathin sections of Lowicryl K4M-embedded tissue. Biotinylated dUTP (Bio-11 dUTP and/or Bio-16-dUTP) was incorporated into mitochondrial rDNA and small nuclear U1 probes by nick-translation. The probes were hybridized to sections of Drosophila ovaries and subsequently detected with an anti-biotin antibody and protein A-gold complex. On semi-thin sections, probe detection was achieved by amplification steps with anti-protein A antibody and protein A-gold with subsequent silver enhancement. At the electron microscope level, specific labeling was obtained over structures known to be the site of expression of the appropriate genes (i.e., either over mitochondria or over nuclei). The labeling pattern at the light microscope level (semi-thin sections) was consistent with that obtained at the electron microscope level. The described nonradioactive procedures for hybrid detection on Lowicryl K4M-embedded tissue sections offer several advantages: rapid signal detection: superior morphological preservation and spatial resolution; and signal-to-noise ratios equivalent to radiolabeling. PMID- 3084497 TI - Posttranslational association of immunoglobulin heavy chain binding protein with nascent heavy chains in nonsecreting and secreting hybridomas. AB - A rat monoclonal antibody specific for immunoglobulin (Ig) heavy chain binding protein (BiP) has allowed the examination of the association of BiP with assembling Ig precursors in mouse B lymphocyte-derived cell lines. The anti-BiP monoclonal antibody immunoprecipitates BiP along with noncovalently associated Ig heavy chains. BiP is a component of the endoplasmic reticulum and binds free intracellular heavy chains in nonsecreting pre-B (mu+, L-) cell lines or incompletely assembled Ig precursors in (H+, L+) secreting hybridomas and myelomas. In the absence of light chain synthesis, heavy chains remain associated with BiP and are not secreted. The association of BiP with assembling Ig molecules in secreting hybridomas is transient and is restricted to the incompletely assembled molecules which are found in the endoplasmic reticulum. BiP loses affinity and disassociates with Ig molecules when polymerization with light chain is complete. We propose that the association of BiP with Ig heavy chain precursors is a novel posttranslational processing event occurring in the endoplasmic reticulum. The Ig heavy chains associated with BiP are not efficiently transported from the endoplasmic reticulum to the Golgi apparatus. Therefore, BiP may prevent the premature escape and eventual secretion of incompletely assembled Ig molecules. PMID- 3084500 TI - Changes in membrane-microfilament interaction in intercellular adherens junctions upon removal of extracellular Ca2+ ions. AB - EGTA-induced depletion of Ca2+ ions from the culture medium of Madin-Darby bovine kidney epithelial cells results in rapid splitting of adherens-type junctions and the detachment of the vinculin- and actin-containing filament bundle from the cytoplasmic faces of the plasma membrane of the zonula adhaerens. This process was monitored by phase-contrast microscopy, combined with electron microscopy and immunofluorescent localization of the two proteins. It is shown that shortly after extracellular free Ca2+ concentration is lowered to the micromolar range, the actin-containing, junction-associated belt of microfilaments, together with the vinculin-rich junctional plaque material, is irreversibly detached as one structural unit from the plasma membrane, contracts, and is displaced towards the perinuclear cytoplasm where it gradually disintegrates. Other actin- and vinculin containing structures present in the same cells, notably the focal contacts at the substratum, are not similarly affected by the Ca2+ depletion and retain both the adhesion to the external surface and the association with the plaque and microfilament components. Electron microscopic examination has shown that the membrane domain of the zonulae adhaerentes, unlike that of desmosomes, is not endocytosed after Ca2+ removal and that the displaced actin- and vinculin containing plaque and filament belt are not associated with a particular membrane. It is further shown that upon restoration of normal Ca2+ levels in the culture medium, new intercellular contacts are established gradually by accretion of both vinculin and actin into new belt-like plaque- and microfilament containing structures. PMID- 3084499 TI - Stress fibers in the splenic sinus endothelium in situ: molecular structure, relationship to the extracellular matrix, and contractility. AB - In the present study, we investigated structural and functional aspects of stress fibers in a cell type in situ, i.e., the sinus endothelium of the human spleen. In this cell type, stress fibers extend underneath the basal plasma membrane and are arranged parallel to the cellular long axis. Ultrastructurally, the stress fibers were found to be composed of thin actin-like filaments (5-8 nm) and thick myosin-like filaments (10-15 nm X 300 nm). Actin filaments displayed changes in polarity (determined by S-1-myosin subfragment decoration), which may allow a sliding filament mechanism. At their plasmalemmal attachment sites, actin filaments exhibited uniform polarity with the S-1-arrowhead complexes pointing away from the plasma membrane. Fluorescence microscopy showed that the stress fibers have a high affinity for phalloidin and antibodies to actin, myosin, tropomyosin, and alpha-actinin. Vinculin was confined to the cytoplasmic aspect of the plasmalemmal termination sites of stress fibers, while laminin, fibronectin, and collagens were located at the extracellular aspect of these stress fiber-membrane associations. Western blot analysis revealed polypeptide bands that contained actin, myosin, and alpha-actinin to be major components of isolated cells. Exposure of permeabilized cells to MgATP results in prominent changes in cellular shape caused by stress fiber contraction. It is concluded that the stress fibers in situ anchored to cell-to-extracellular matrix contacts can create tension that might allow the endothelium to resist the fluid shear forces of blood flow. PMID- 3084501 TI - Identification of actin-, alpha-actinin-, and vinculin-containing plaques at the lateral membrane of epithelial cells. AB - In this paper, a new type of spot desmosome-like junction (type II plaque) is described that is scattered along the entire lateral plasma membrane of rat and human intestinal epithelium. Ultrastructurally type II plaques differed from the classical type of epithelial spot desmosome ("macula adherens", further denoted as type I desmosome) by weak electron density of the membrane-associated plaque material, association of the plaques with microfilaments rather than intermediate filaments, and poorly visible material across the intercellular space. Thus, type II plaques resemble cross-sections of the zonula adherens. Immunofluorescence microscopic studies were done using antibodies to a main protein associated with the plaques of type I desmosomes (desmoplakin I) and to the three major proteins located at the plaques of the zonula adherens (actin, alpha-actinin, and vinculin). Two types of plaques were visualized along the lateral surface of intestinal and prostatic epithelium: (a) the type I desmosomes, which were labeled with anti-desmoplakin but did not bind antibodies to actin, alpha actinin, and vinculin, and (b) a further set of similarly sized plaques, which bound antibodies to actin, alpha-actinin, and vinculin but were not stained with anti-desmoplakin. Three-dimensional computer reconstruction of serial sections double-labeled with anti-desmoplakin and anti-alpha-actinin further confirmed that both types of plaques are spatially completely separated from each other along the lateral plasma membrane. The computer graphs further revealed that the actin-, alpha-actinin-, and vinculin-containing plaques have the tendency to form clusters, a feature also typical of type II plaques. It is suggested that the type II plaques represent spot desmosome-like intercellular junctions, which, like the zonula adherens, appear to be linked to the actin filament system. As the type II plaques cover a considerable part of the lateral cell surface, they might play a particular role in controlling cellular shape and intercellular adhesion. PMID- 3084504 TI - AIDS and Asclepiads. PMID- 3084502 TI - Disialoganglioside GD2 distributes preferentially into substrate-associated microprocesses on human melanoma cells during their attachment to fibronectin. AB - Human melanoma cells (M21) actively attach and spread on a fibronectin substrate. Indirect immunofluorescence assays with specific monoclonal antibodies directed to the disialoganglioside GD2, the major ganglioside expressed on M21 melanoma cells, indicate that during the cell attachment process this molecule redistributes into microprocesses that make direct contact with the fibronectin substrate. Scanning and transmission immunoelectron microscopic studies with anti GD2 monoclonal antibodies and immuno-gold staining demonstrate that GD2 preferentially localizes into substrate-associated microprocesses that emanate from the plasma membrane of the M21 cells. Staining with monoclonal antibodies directed to other melanoma surface antigens fails to demonstrate a similar distribution pattern on these cells. Direct evidence is provided that GD2 is involved in M21 cell attachment to fibronectin, since treatment of these cells with anti-GD2 monoclonal antibodies causes cell rounding and detachment from a fibronectin substrate. Moreover, scanning electron microscopy demonstrates that this loss of attachment of fibronectin is characterized by a perturbation of the cell attachment-promoting microprocesses that in the presence of these antibodies lose contact with the fibronectin substrate. PMID- 3084505 TI - Bullous skin ulceration in man with myelofibrosis. PMID- 3084503 TI - Interaction between Raf and Myc oncogenes in transformation in vivo and in vitro. AB - 3611 MSV, a raf-oncogene-transducing murine retrovirus, induces fibrosarcomas and erythroid hyperplasia in newborn mice after a latency of 4-8 wk. In contrast, new recombinant murine retroviruses carrying the myc oncogene (J-3, J-5 construct viruses) do not induce tumors before greater than 9 wk. A combination of both oncogenes in an infectious murine retrovirus (J-2) induces hematopoietic neoplasms in addition to less prominent fibrosarcomas and pancreatic adenocarcinoma 1-3 wk after inoculation. The hematologic neoplasms consist of immunoblastic lymphomas of T and B cell lineage and erythroblastosis. If animals were inoculated with a variant of the J-3 virus, which induces altered foci in cultures of NIH 3T3 cells, carcinoma developed in the pancreas with a 2-6 mo latency. In parallel to the synergistic action of both oncogenes on hematopoietic cells in vivo, we find that raf-oncogene-induced transformation of bone marrow cells in culture is enhanced by the addition of myc, which by itself does not transform these cells when grown in standard media. We conclude that concomitant expression of raf and myc oncogenes in hematopoietic and epithelial cells alters their respective transforming activities. The contribution of v-myc in this synergism was examined by use of a series of recombinant murine retroviruses capable of expressing the avian v-myc to study the effect of altered myc expression on hematopoietic/lymphoid cells. With either interleukin 3- or interleukin 2-dependent cell lines, introduction of the recombinant viruses abrogated the requirement for IL 3 or IL 2 for growth, and associated with this was the suppression of c-myc expression. The findings suggest that myc is a component in the signal transduction pathway for IL 3 and IL 2 and support an autoregulatory mechanism of c-myc expression. In contrast to v-myc, expression of v-raf in primary lymphoid/hematopoietic cells has an immortalizing function without abrogating the requirement for IL 3 for growth. This suggests that v-raf and v-myc affect different components of growth regulation, as, for example, commitment (v-myc) and cell cycle progression (v-raf). PMID- 3084506 TI - The cloning of factor VIII and the genetics of hemophilia A. PMID- 3084507 TI - Addisonian crisis after thyroid replacement. PMID- 3084508 TI - A prolonged infection after valve replacement. PMID- 3084509 TI - Familial polyposis. PMID- 3084510 TI - Renal rescue by Reverend Bayes. PMID- 3084511 TI - Elusive chromosome anomalies. PMID- 3084512 TI - Postoperative supraventricular tachycardia. PMID- 3084513 TI - Pulmonary edema. AB - The pathophysiology of pulmonary edema formation has been discussed under normal conditions and when pulmonary capillary endothelial (and possibly alveolar epithelial) permeability are increased. The potential anatomic sites for pulmonary edema formation and the clinical relevance of the various sites were discussed. The role of potential "safety factors"--including increased lung lymph flow, increased interstitial hydrostatic pressure, and decreased interstitial protein osmotic pressure--in cardiogenic and fluid overload versus increased permeability pulmonary edema, were addressed. The clinical usefulness of quantitating various variables including pulmonary vascular pressures and lung water were also briefly discussed. Pulmonary edema fluid contains potential mediators that may contribute to the severity and chronicity of the lung injury. It is hoped that the concepts explored here should eventually provide clinically relevant information to guide in the management of critically ill patients with pulmonary edema. PMID- 3084514 TI - Procedures used in the diagnosis of pain. PMID- 3084515 TI - Extreme pyrexia. PMID- 3084516 TI - A malignant diarrhea from the Third World. PMID- 3084517 TI - Doctors and stress: sources and solutions. PMID- 3084518 TI - Alopecia: common and uncommon. PMID- 3084519 TI - Neurologic injuries in boxers. PMID- 3084520 TI - Exercise and the insulin-dependent diabetic. PMID- 3084521 TI - Two gay patients with demyelinating disorders. PMID- 3084522 TI - Primary degenerative dementia. PMID- 3084523 TI - Clinical breast examination. PMID- 3084524 TI - When to treat mild hypertension. PMID- 3084525 TI - Management of massive gastrointestinal bleeding. PMID- 3084526 TI - Comparison and critical evaluation of six published extraction and clean-up procedures for aflatoxin M1 in liquid milk. AB - A practical evaluation has been carried out of six previously published extraction and clean-up methods for aflatoxin M1 in liquid milk. The procedures evaluated incorporated the most widely used stages of clean-up including solvent extraction and silica gel chromatographic clean-up, selective solvent extraction of the extracted residue, the use of deproteination prior to hydrophilic column liquid-liquid partition or solvent extraction and the use of pre-packed reversed phase cartridges for the direct extraction of aflatoxin M1 from the milk. Analysis times for each method, recoveries and relative costs are reported together with fluorescence high-performance liquid chromatography chromatograms, obtained under identical conditions to compare the relative cleanliness of the final extracts produced by each method. A pre-packed reversed phase cartridge method was shown to be the most satisfactory in terms of speed, cost and cleanliness of the final residue. PMID- 3084527 TI - Continuous-flow monitoring of hexuronic acid by carbazole reaction during gel filtration of proteoglycans in urea solutions. PMID- 3084528 TI - Sensitive reversed-phase high-performance liquid chromatographic determination of aflatoxin M1 in dry milk. PMID- 3084529 TI - Capillary gas chromatography-mass spectrometry of valproic acid metabolites in serum and urine using tert.-butyldimethylsilyl derivatives. AB - A quantitative method has been developed for valproic acid and twelve of its metabolites using capillary gas chromatography--mass spectrometry with selected ion monitoring. The method is applicable to serum or urine and all metabolites are measured in a single run. Ions selected for quantitative purposes were the characteristic (M-57)+ ions of the tert.-butyldimethylsilyl (tBDMS) derivatives. The 4-hydroxyvalproic acid was measured as the gamma-lactone. Calibration curves were found to be linear and the sensitivities in the order of 0.1 microgram/ml. Patient data are presented. A comparison of tBDMS and trimethylsilyl (TMS) derivatives showed that tBDMS gave superior sensitivity for the unsaturated metabolites and a shorter analysis time. Mixed tBDMS-TMS derivatives were also investigated. PMID- 3084530 TI - Prolactin-releasing action of gonadotropin-releasing hormone in hypogonadal women. AB - To gain insight into the PRL-releasing effect of GnRH, serum PRL and gonadotropin responses to a 10-microgram iv bolus dose of exogenous GnRH were studied in hypergonadotropic hypogonadal women (HHW) and patients with functional hypothalamic amenorrhea (FHA). The results were compared with those obtained in normal cycling women during the early follicular phase of the cycle. GnRH induced a significant increase in PRL levels (P less than 0.001) in HHW compared to early follicular phase women, in whom no significant response occurred. In HHW, the maximal PRL percent increment was positively correlated with the ratio of the maximal percent increments of FSH and LH (r = 0.93). GnRH induced a significant increase in PRL levels in every FHA patient, but in four of them (high PRL responders), the PRL response was at least 5-fold greater than in the other six (low PRL responders). The clinical profiles, basal hormone concentrations, and LH responses to GnRH were similar in these two groups of FHA patients, but the FSH response to GnRH was greater (P less than 0.05) in the high PRL responders. The maximal percent increment of PRL was also positively correlated with the maximal percent increment of FSH (r = 0.76; P = 0.01). These data demonstrate that in these two hypogonadal models, the PRL response to exogenous GnRH corresponds to the FSH response and suggests that GnRH-stimulated PRL release may be mediated by a paracrine effect between FSH-enriched gonadotrophs and lactotrophs. PMID- 3084531 TI - Morphological studies on mixed growth hormone (GH)- and prolactin (PRL)-secreting human pituitary adenomas. Coexistence of GH and PRL in the same secretory granule. AB - A morphological study was carried out on five mixed GH- and PRL-secreting pituitary adenomas, surgically removed from acromegalic patients with hyperprolactinemia, in order to verify whether the two hormones were contained in the same cell or in different cells. Double labeling with the protein A-gold immunotechnique was used to visualize the ultrastructural localization of the two hormones on ultrathin sections of the tumors. By means of this high resolution technique we found in all adenomas the presence of numerous (from 50-80% of the whole cell population) mammosomatotrophs, i.e. cells containing simultaneously PRL and GH. The occurrence of cells producing only GH (in four tumors) or only PRL (in one tumor) was also observed. In mixed cells GH and PRL were segregated in the same mixed granule. In one tumor granules positive only for GH together with mixed granules were found in the same cell. Immunofluorescence studies, at the light microscopic level, allowed us to clearly identify mammosomatotrophs only in two tumors. Double labeling using the gold immunotechnique appears therefore to be the most suitable experimental approach to detect the existence of mixed cells in plurihormonal adenomas. Our results support the idea that the frequency of mixed adenomas with mixed cells may be higher than that believed previously. The simultaneous presence of two hormones in the same secretory granule could explain why, in patients having mixed tumors, factors able to stimulate or inhibit the release of one hormone can also stimulate or inhibit the secretion of the other. PMID- 3084532 TI - Interferon-gamma induces the expression of HLA-A,B,C but not HLA-DR on human pancreatic beta-cells. AB - We examined the effect of interferon-gamma (IFN gamma) on expression of the major histocompatibility proteins on cultured human islet cells isolated from adult and fetal pancreas and from an insulinoma. While the pancreatic beta-cells from different sources varied in their responses to IFN gamma, in all instances the expression of HLA-A,B,C protein was increased. Pancreatic beta-cells did not express HLA-DR protein, before or after culture of the islets in IFN gamma, although HLA-DR protein expression was induced on some non-beta-cells. These findings are at variance with those reported with thyroid follicular cells, in which IFN gamma induced expression of HLA-DR. We, therefore, conclude that the interaction between the immune and the endocrine systems may be endocrine cell specific. The up-regulation of HLA-A,B,C protein on beta-cells by IFN gamma provides a mechanism for enhanced targetting to the beta-cells of autoreactive cytotoxic T-lymphocytes and, hence, for amplifying beta-cell destruction. PMID- 3084533 TI - Growth hormone (GH) response to GH-releasing hormone in children with subnormal integrated concentrations of GH. AB - We determined the GH responses to human GH-releasing hormone-40 (GHRH) in poorly growing children who had either normal or deficient GH secretion, as measured by pharmacological stimulation and integrated concentration of GH (IC-GH). Ten patients had both normal pharmacologically stimulated GH and IC-GH (GH-normal), 15 patients had normal pharmacologically stimulated GH but deficient IC-GH [GH neurosecretory dysfunction (GHND)], and the remaining 7 patients had both subnormal stimulated GH and IC-GH [GH deficiency (GHD)]. The mean peak plasma GH response to GHRH was 11.7 +/- 8.5 (+/- SD) ng/ml in GHD patients, significantly lower than the responses of both the GHND (49.2 +/- 39.2 ng/ml; P less than 0.0001) and GH-normal (51.8 +/- 44 ng/ml; P less than 0.0001) groups. The range of peak GH responses to GHRH in GHD patients overlapped the lower end of the range of responses in the GHND and GH-normal patients. Three GH-normal and eight GHND patients had greatly enhanced GH responses to GHRH (greater than 50 ng/ml); no GHD patients had a response over 24.2 ng/ml. There was no difference between the GH responses of male and female patients within groups to GHRH. There was a significant correlation between the log of the peak GH response to GHRH and the log of the maximal GH response to standard pharmacological stimuli (r = 0.51; P less than 0.005). Because of the variability of GH responses to GHRH encountered among the patients, the response to GHRH cannot be used as a test for identifying patients with inadequate spontaneous GH secretion. The IC-GH is the only method that can identify children with GHND. PMID- 3084534 TI - Characterization of the physiological pattern of episodic gonadotropin secretion throughout the human menstrual cycle. AB - To characterize the spectrum of pulsatile gonadotropin secretion during the course of the normal menstrual cycle, we studied normal women during 51 ovulatory cycles. Plasma gonadotropin concentrations were measured at 10-min intervals for 20-24 h during the early, mid-, and late follicular phases and the early, mid-, and late luteal phases. LH data series were analyzed using 2 different computer assisted algorithms for pulse detection. The LH interpulse interval decreased during the follicular phase (FP) from 94 +/- 4 (+/- SEM) min in the early FP (EFP) to 71 +/- 4 min by the late FP (LFP; P less than 0.001). The estimation of LH pulse frequency in the EFP was significantly affected by slowing of episodic LH secretion during sleep. In the luteal phase (LP), the LH interpulse interval progressively increased from 103 +/- 8 min in the early LP (ELP) to 216 +/- 39 min by the late LP (LLP; P less than 0.001). Sleep-associated slowing of episodic LH secretion also occurred in the ELP. The mean LH pulse amplitude in the EFP (6.5 +/- 0.4 mIU/ml) decreased significantly by the midfollicular phase (MFP; 5.1 +/- 0.8 mIU/ml; P less than 0.05) and increased once again by the LFP (7.2 +/- 1.2 mIU/ml). LH pulse amplitude was highest in the ELP (14.9 +/- 1.7 mIU/ml), decreased by the midluteal phase (MLP) to 12.2 +/- 2.0 mIU/ml, and declined further by the LLP to 7.6 +/- 1.1 mIU/ml (P less than 0.001 vs. ELP). FSH secretion was significantly (P less than 0.05) correlated with LH secretion at time lags of 0-10 min in 82% of the studies. These results indicate the following. 1) In the EFP and ELP, the frequency of gonadotropin pulsations is reduced at night in association with sleep. 2) The frequency of LH secretion increases from the EFP to MFP and LFP. 3) LH pulse amplitude decreases in the MFP, suggesting enhanced negative feedback of estrogen on the hypothalamic pituitary axis and/or a decrease in GnRH secretion at this stage. 4) A progressive reduction of LH pulse frequency and amplitude occurs during the LP which is correlated with the duration of exposure of the hypothalamic-pituitary axis to progesterone. 5) A close relationship exists between secretion of LH and FSH, suggesting a common stimulatory factor for both gonadotropins. PMID- 3084535 TI - Chronic human chorionic gonadotropin administration in normal men: evidence that follicle-stimulating hormone is necessary for the maintenance of quantitatively normal spermatogenesis in man. AB - The role of FSH in the maintenance of spermatogenesis in man is poorly understood. To determine whether normal serum levels of FSH are necessary for the maintenance of quantitatively normal spermatogenesis, we first studied the effect on sperm production of selective FSH deficiency induced by chronic administration of hCG in normal men. Then, we determined the effect of FSH replacement in some of these men. After a 3-month control period, eight normal men (aged 30-39 yr) received 5000 IU hCG, im, twice weekly for 7 months. Then while continuing the same dosage of hCG, subjects simultaneously received 200 mg testosterone enanthate (T), im, weekly for an additional 6 months. hCG administration alone resulted in partial suppression of the mean sperm concentration from 88 +/- 24 (+/-SEM) million/ml during the control period to 22 +/- 7 million/ml during the last 4 months of hCG treatment (P less than 0.001 compared to control values). With the addition of T to hCG, sperm counts remained suppressed to the same degree. Except for one man who became azoospermic while receiving hCG plus T, sperm motilities and morphologies remained normal in all subjects throughout the entire study. During both the hCG alone and hCG plus T periods, serum FSH levels were undetectable (less than 25 ng/ml), and urinary FSH levels were comparable to those in prepubertal children and hypogonadotropic hypogonadal adults. We replaced FSH activity in four of the eight men in whom prolonged selective FSH deficiency and partial suppression of sperm production were induced by hCG administration. Immediately after the period of hCG plus T administration, T was stopped in four men who continued to receive hCG alone (5000 IU, im, twice weekly) for 3 months. Then, while continuing the same dosage of hCG, these men received 100 IU human FSH, sc, daily (n = 2) or 75 IU human menopausal gonadotropin, sc, daily (n = 2) for 5-8 months. During the second period of hCG administration alone, serum FSH levels were undetectable (less than 25 ng/ml), and sperm concentrations were suppressed (34 +/- 13 million/ml) compared to the control values for these four men (125 +/- 39 million/ml; P less than 0.001). With the addition of FSH to hCG, FSH levels increased (213 +/- 72 ng/ml) and sperm concentrations rose significantly, reaching a mean of 103 +/- 30 million/ml (P less than 0.03 compared to hCG alone).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3084536 TI - Role of the kidneys in the metabolism of circulating mevalonate in humans. AB - Previous studies in several animal species have demonstrated that the kidneys are the primary site of mevalonate metabolism by the oxidative or shunt pathway. To determine the role of the human kidney in mevalonate oxidation, we studied mevalonate shunt activity in patients undergoing hemodialysis for varying degrees of renal failure. Surprisingly, at least half of the uremic patients and even anephric patients had normal ability to oxidize mevalonate by the shunt pathway. In addition, we found a strong negative correlation (R = -0.94) between mevalonate shunt activity and serum phosphorus levels in uremic patients. The resulting inhibition of mevalonate oxidation by high serum phosphorus levels was reversed by lowering the serum phosphorus in one patient. Finally, a positive correlation was found between mevalonate oxidation and serum PTH levels. The results of this study suggest that, in humans, extrarenal tissues can be major contributors to mevalonate oxidation. It is therefore probable that in humans, in contrast to other animals, the kidney is not the primary site of mevalonate metabolism by this oxidative pathway. Finally, the strong negative correlation between serum phosphorus levels and the ability of uremic patients to oxidize mevalonate suggests a regulatory role for the phosphate ion in the mevalonate shunt pathway. PMID- 3084537 TI - Serum bioactive follicle-stimulating hormone during the human menstrual cycle and in hyper- and hypogonadotropic states: application of a sensitive granulosa cell aromatase bioassay. AB - A sensitive in vitro assay based on the stimulation of estrogen production by cultured rat granulosa cells was recently developed for the measurement of biologically active FSH. This bioassay system is specific for FSH, highly sensitive, and capable of measuring basal FSH levels in rat serum. The granulosa cell aromatase bioassay was improved by the use of additives known to enhance FSH activity and by pretreatment of serum with 12% polyethylene glycol to remove inhibitory substances. We applied this method to the measurement of bioactive FSH levels in serum samples from human subjects. As determined in daily blood samples during ovulatory menstrual cycles in seven women, bioactive FSH levels exhibited a pattern closely resembling that of immunoreactive FSH. The mean bioactive serum FSH levels were 29.9, 20.5, 39.2, and 14.8 mIU/ml for the early follicular phase, late follicular phase, preovulatory surge, and luteal phase, respectively. The bio- to immunoratio (B:I) throughout the menstrual cycle ranged from 1.4-3.4, with a mean of 2.5. The ratios for early follicular phase, late follicular phase, preovulatory surge, and luteal phase were 2.7, 2.3, 1.4, and 2.6, respectively. The correlation coefficient (r) of the serum FSH values obtained by bioassay and RIA was 0.91. FSH bioactivity was also measured in patients in each of the following categories with the following mean values: oral contraceptive pill users (undetectable), hypothalamic amenorrhea (18.7 mIU/ml; B:I, 2.6), premature ovarian failure (163 mIU/ml; B:I, 1.7), and postmenopausal women (191 mIU/ml; B:I, 1.6). These findings suggest that measurement of immunoreactive FSH levels correctly reflects the biological activity of FSH in serum of cycling women and patients in certain hyper- and hypogonadotropic states. The granulosa cell aromatase bioassay represents a new tool for future assessments of biologically active FSH in physiological and pathophysiological conditions. PMID- 3084538 TI - The dependency of folliculogenesis and corpus luteum function on pulsatile gonadotropin secretion in cycling women using a gonadotropin-releasing hormone antagonist as a probe. AB - A potent GnRH antagonist, [Ac-delta 3-Pro1,p-F-D-Phe2,D-Trp3,6]GnRH (4F-Antag), was used as a probe to determine the relative dependency of ovarian cyclicity on pulsatile gonadotropin secretion. 4F-Antag was administered in a dose of 80 micrograms/kg sc twice a day for 3 consecutive days during different phases of the menstrual cycle. This treatment resulted in a prompt attenuation of pulsatile gonadotropin secretion in all women studied. Maximal suppression of gonadotropin levels, expressed as percent change from baseline, averaged 48% for LH and 22% for FSH. The reduced pulsatile gonadotropin release induced by 4F-Antag administration during the early follicular phase resulted in a significant decrease in serum estradiol levels during the period of treatment and was followed by a prolongation of follicular phase (2.4 days) and cycle length (3.5 days), but no alteration of subsequent cyclic ovarian steroid profiles compared to control cycles. Treatment initiated during the midfollicular phase 4-6 days before the expected LH surge resulted in a more dramatic decline in serum estradiol levels and prolongation of follicular phase length by 5-6 days compared to control cycles. Normal luteal function was preserved. These alterations were compatible with induction of the demise of the dominant follicle followed by the reinitiation of follicular recruitment. Administration of 4F-Antag during the midluteal phase resulted in rapid falls in serum estradiol and progesterone levels and the onset of menstrual bleeding in all women. The luteolytic effect of 4F-Antag was completely negated by the administration of hCG. These data indicate that 4F-Antag interferes with ongoing cyclic ovarian function by reducing pulsatile gonadotropin stimulation, which disrupts folliculogenic processes and induces the demise of the corpus luteum. From these findings we infer that the functional integrity of ovarian cyclicity is remarkably sensitive to brief (3 days) and partial reduction in pulsatile gonadotropin secretion. PMID- 3084539 TI - Long term follow-up of women with surgically treated prolactin-secreting pituitary tumors. AB - To examine the long term effectiveness of transsphenoidal microsurgery for patients with PRL-secreting pituitary tumors, we studied 54 women at yearly intervals after transsphenoidal surgery. Five years after surgery, 19 women (35%) had normal serum PRL concentrations, and 23 (43%) had persistent hyperprolactinemia. Hyperprolactinemia recurred in 12 of 31 patients (39%) who had normal PRL concentration 6 weeks after surgery. None of the patients with recurrent hyperprolactinemia had radiographic evidence of tumor regrowth, and only 3 of 12 had amenorrhea. A serum PRL level below 6 ng/ml 6 weeks after surgery occurred more frequently in cured patients than in those who had a recurrence. PRL responses to TRH were normal in cured patients 1 and 5 yr after surgery and abnormal in those who had recurrent hyperprolactinemia. The PRL responses to chlorpromazine- and insulin-induced hypoglycemia were blunted in patients with normal as well as elevated PRL levels. Patients with recurrent, as well as those with persistent, hyperprolactinemia had no nocturnal rise in serum PRL 5 yr after surgery. The 39% recurrence rate of hyperprolactinemia and persistent abnormalities in pituitary-hypothalamic regulation of PRL secretion after transsphenoidal surgery raise important questions about the choice of primary therapy for patients with PRL-secreting tumors. PMID- 3084540 TI - Sex hormone-binding protein in hyperthyroxinemic patients: a discriminator for thyroid status in thyroid hormone resistance and familial dysalbuminemic hyperthyroxinemia. AB - Sex hormone-binding globulin (SHBG) levels in serum are affected by thyroid status; hyperthyroidism is associated with high SHBG levels, whereas hypothyroid patients have low or normal SHBG levels. This study was undertaken to test the usefulness of SHBG determinations to define the thyroid status in two hyperthyroxinemic states: thyroid hormone resistance (THR) and familial dysalbuminemic hyperthyroxinemia (FDH). Serum SHBG levels were determined in 193 patients and 26 normal subjects using an IRMA-type RIA. In the control group, the mean values in women (58.9 nmol/liter) and men (32.7 nmol/liter) were significantly different (P less than 0.001). In adult subjects with THR, SHBG levels were within the normal range, with mean values of 54.8 nmol/liter (range, 28.7-82.5 nmol/liter) in women and 18 and 20 nmol/liter in two men. In FDH subjects, the mean SHBG levels did not differ from the normal values; they averaged 60.7 nmol/liter in women and 42.3 nmol/liter in men. From these data we conclude that in THR and FDH, free T4 levels elicit an appropriate hepatic response corresponding to the euthyroid status of these subjects. SHBG determination may, therefore, serve as an in vitro test for end-organ sensitivity to thyroid hormones. PMID- 3084541 TI - Calcium-regulating hormones across the menstrual cycle. AB - Midcycle elevations of serum PTH, calcitonin (CT), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] in women have been reported. To examine the effects of cyclic changes in ovarian steroid secretion on calcitropic hormone concentrations, we used a cytoreceptor assay for 1,25-(OH)2D and homologous RIAs for PTH and CT to measure these hormones in daily blood samples obtained from six women throughout the menstrual cycle. Significant changes in serum PTH, CT, 1,25-(OH)2D, calcium, and phosphorus concentrations during the cycle were not found; transverse means (+/- SE) were 101 +/- 3.5 pg/ml for PTH, 30.8 +/- 1.8 pg/ml for CT, and 40.1 +/- 1.7 pg/ml for 1,25-(OH)2D. In addition, CT reserve was assessed by calcium infusion (3 mg/kg, iv, in 10 min) during the early and late follicular and midluteal phases of the cycle. Although serum CT increased significantly (P less than 0.01) after calcium infusion, the mean (+/- SE) increment (23.2 +/- 2.2 pg/ml) did not significantly differ in the three phases of the cycle (early follicular, 23.8 +/- 4.0; late follicular, 23.3 +/- 3.4; midluteal, 22.5 +/- 4.1). Our data do not support previous reports of midcycle elevations in serum PTH, CT, and 1,25-(OH)2D concentrations, and we conclude that serum concentrations of the calcitropic hormones do not significantly vary during the menstrual cycle. PMID- 3084542 TI - Use of gonozyme on urine sediment for diagnosis of gonorrhea in males. AB - We compared enzyme immunoassay (Gonozyme; Abbott Laboratories, North Chicago, Ill.) for detection of gonococcal antigen in urine sediments with urethral swab culture for diagnosis of gonorrhea in men attending a venereal disease clinic. The prevalence of infection was 14% by culture (27/196). The sensitivity of enzyme immunoassay was 93% (25/27) compared with the culture method, and the specificity was 99% (167/169). The ability to detect gonococcal antigen in urine sediment may provide the basis for a noninvasive method of screening for gonococcal infection. PMID- 3084543 TI - Growth of Neisseria gonorrhoeae on Campylobacter medium at 40 degrees C. AB - As the result of finding Neisseria gonorrhoeae in a rectal culture for Campylobacter spp., a study was done to determine if this was an unusual isolate. Five gonococcal isolates grew equally well on modified Thayer-Martin medium in a microaerobic chamber whether incubated at 35 or 40 degrees C. All five grew as well as controls microaerobically on campylobacter medium containing lysed horse blood at 35 degrees C; three of the five grew on this medium at 40 degrees C. PMID- 3084544 TI - Influence of patient hemogram on growth index values generated from a radiometric detection device. AB - Blood samples from 20 patients with widely varying concentrations of erythrocytes and leukocyte subtypes were inoculated into BACTEC 6B bottles (Johnston Laboratories, Inc., Towson, Md.). There was no relationship between growth index value and hemogram. Although sterile blood is capable of generating small amounts of 14CO2, the mechanism for this phenomenon is not related to the concentration of a specific type of blood cell. PMID- 3084545 TI - New method of preparing elastase toxoid from Pseudomonas aeruginosa. AB - A new method for the preparation of elastase toxoid of Pseudomonas aeruginosa was developed. A chloroacetyl peptide derivative (CICH2CO-HOLeu-Ala-Gly-NH2; HOLeu, N hydroxy-L-leucine), an active-site-directed irreversible inhibitor of Pseudomonas aeruginosa elastase, was used to prepare elastase toxoid with or without pretreatment with Formalin and L-lysine. Elastase toxoid thus obtained appeared to be ideal, possessing negligible enzyme activity while retaining full antigenicity and immunogenicity. PMID- 3084546 TI - Distribution of bacteria and yeasts within the 10-ml Isolator during the processing of seeded blood samples. AB - Forty-five organisms consisting of stock cultures and clinical isolates of bacteria and yeast were separately inoculated into outdated blood bank blood to achieve a concentration of approximately 100 CFU/ml. Blood with each organism was introduced into groups of four Isolators (E. I. du Pont de Nemours & Co., Inc., Wilmington, Del.), which were then processed according to the Isostat instructions of the manufacturer. The supernatant, sediment, and wash (material removed from the surface of the slanted stopper after sediment removal) were inoculated onto 5% sheep blood agar plates. Cultures were incubated aerobically (5 to 10% CO2) at 35 degrees C for 48 to 72 h. From the 180 Isolators, the mean recovery was 6% (range, 0 to 48%) for the supernatant, 87% (range, 47 to 98%) for the sediment, and 8% (range, 3 to 23%) for the wash. Neither variation among technologists nor intentional misalignment of additional Isolators in the centrifuge could explain all of the losses of microorganisms from the sediment. The manual nature of the Isolator procedure, which led to the loss of significant amounts of organisms from the sediment, may help to explain false-negative Isolator results obtained from blood of patients, particularly when small numbers of pathogens are present. PMID- 3084547 TI - Comparison of quantitative and semiquantitative culture techniques for burn biopsy. AB - Accurate evaluation of bacterial colonization as a predictive index for wound sepsis has relied on a quantitative culture technique that provides exact colony counts per gram of tissue by culture of five serial dilutions of biopsy tissue homogenate. The method, while useful to the physician, is both labor intensive and expensive. In this study 78 eschar biopsies were cultured by a semiquantitative technique that involved the use of 0.1- and 0.01-ml samples of inocula and by the serial dilution method. Exact colony counts from the semiquantitative culture method were available only from cultures containing 10(4) to 10(6) CFU/g of tissue. Other colony counts were reported as less than 10(4) or greater than 10(6) CFU/g. Agreement by category of colony counts between the two methods was 96%. For prediction of wound sepsis, the semiquantitative procedure had a positive predictive value of 100% and a negative predictive value of 93.7%. This method also resulted in an approximately 30% reduction of work units (as defined by the College of American Pathologists) and a 60% reduction in the amount of media for specimen processing. Therefore, this semiquantitative culture technique provides accurate information to the physician while saving both time and materials. PMID- 3084548 TI - Clinical comparison of a new automated infrared blood culture system with the BACTEC 460 system. AB - A new blood culture instrument, the BACTEC (Johnston Laboratories, Inc., Towson, Md.) NR-660, which utilizes infrared detection of carbon dioxide from microbial metabolism, was compared with the radiometric BACTEC 460 system. There were 1,554 isolates from 18,785 paired aerobic blood cultures. Of these isolates, 1,303 were isolated from the radiometric 6B medium, and 1,259 were isolated from the NR6A medium (P = 0.06). Analysis of the data indicated no significant differences in recovery when any individual species was considered. When organisms were considered as groups, there were no significant detection differences for gram negative bacilli, yeasts, or anaerobes. For gram-positive cocci in aerobic medium, the BACTEC 460 detected 84.3% of the total isolates, and the BACTEC NR 660 detected 79.7% (P = 0.04). There were 891 isolates from 13,983 paired anaerobic blood cultures. Of these isolates, 725 were recovered from the radiometric 7D BACTEC medium, and 723 were recovered from the NR7A BACTEC medium (P greater than 0.9). In the anaerobic media there was no significant difference in detection of any organism group, including the gram-positive cocci. When the results of the aerobic and anaerobic media were combined, there was equivalence between the two systems for the detection of gram-positive cocci (P greater than 0.2) and other organism groups. When the ability to detect septic episodes was compared, there was no significant difference for any organism group (P = 0.12). For aerobic media, the mean times for detection were 30.5 and 29.5 h for the BACTEC 460 and NR-660, respectively. For anaerobic media, the mean times for detection were 39.8 and 41.6 h for the BACTEC 460 NR-660, respectively. Compared with the BACTEC 460, the BACTEC NR-660 system had a greater ease of operation, faster test cycle, computerized data base, and equally rapid detection of positive cultures. PMID- 3084549 TI - Exoantigen test for Cladosporium bantianum, Fonsecaea pedrosoi, and Phialophora verrucosa. AB - Exoantigens from 10-day-old cultures of 100 isolates of pathogenic and saprophytic dematiaceous fungi were analyzed by the exoantigen test. Antisera to Cladosporium bantianum ATCC 10958, Fonsecaea pedrosoi CDC AMO-B06, and Phialophora verrucosa CDC AMO-C12 were prepared in New Zealand rabbits immunized with soluble antigens from 1-month-old cultures. Absorbed and nonabsorbed antisera and exoantigens from the same organisms were used as reference reagents. Serologic reactions were analyzed in terms of the presence or absence of lines of identity or nonidentity. These reactions allowed presumptive differentiation of C. bantianum, F. pedrosoi, and Phialophora verrucosa from other dematiaceous fungi, including Cladosporium spp. (28 isolates), Exophiala spp. (18 isolates), Fonsecaea spp. (17 isolates). Lecythophora hoffmannii (4 isolates), Phaeoannellomyces werneckii (3 isolates), Phialophora spp. (17 isolates), Wangiella dermatitidis (9 isolates), and Rhinocladiella spp. (4 isolates). PMID- 3084550 TI - Microbiological assessment of 24- and 48-h changes and management of semiclosed circuits from ventilators in a neonatal intensive care unit. AB - The contamination of semiclosed disposable circuits of Healthdyne and Bourns ventilators was studied in a newborn intensive care unit over a 2-year period. A total of 379 fluid samples was obtained from inspiratory and expiratory tubing condensates and traps and from thermal humidifier columns fed with prefilled containers of sterile water. In addition, 100 tryptic soy agar plates were exposed to the exhalation mist of the circuits sampled. With 24-h changes of circuits a 2.5% contamination rate was observed (phase I). In an effort to contain costs, circuits were changed every 48 h (phase II); the concentration of potential pathogens increased to greater than 10(5) CFU/ml with this extension of changing time. Two long-term (15- and 9-month) infants were colonized and intermittently infected, one with Klebsiella pneumoniae and Staphylococcus aureus and the other with Pseudomonas aeruginosa. When the protocol was readjusted from 48- to 24-h circuit changes (phase II), the contamination rate decreased; for the two colonized infants (35 circuits, 123 samples) the contamination rate decreased from 19 to 6% (P less than 0.01; chi-square test), and for seven noncolonized infants (59 circuits, 217 samples) the contamination rate decreased from 5 to 0.5% P less than 0.001; (chi-square test). These data suggest that frequent changing of the circuits reduces colonization and cross-infection. PMID- 3084551 TI - Isolation of Corynebacterium aquaticum from spinal fluid of an infant with meningitis. AB - A 4-week-old female was hospitalized because of vomiting, irritability, and nuchal rigidity. A spinal fluid culture yielded Corynebacterium aquaticum. The diagnosis of C. aquaticum meningitis in this infant was supported by the following cerebrospinal fluid findings: Gram stain, elevated protein, hypoglycorrhachia, positive C-reactive protein, and polymorphonuclear leukocytosis. Antigen studies for common bacterial causes of meningitis were negative. C. aquaticum is a rare cause of human disease and may be initially confused with Listeria monocytogenes, which is a more common gram-positive, motile rod associated with meningitis in infants. PMID- 3084552 TI - Evaluation of streptomycin and ethambutol concentrations for susceptibility testing of Mycobacterium tuberculosis by radiometric and conventional procedures. AB - Clinical isolates of Mycobacterium tuberculosis were used to compare various concentrations of streptomycin and ethambutol in the BACTEC 460 (Johnston Laboratories, Inc., Towson, Md.) radiometric method for drug susceptibility testing with those in the conventional method. Streptomycin used at 2.0 micrograms/ml for both methods showed a 0.99 agreement with susceptible strains and a 0.97 agreement with resistant strains. Ethambutol used at 2.5 micrograms/ml for the radiometric method showed 1.00 agreement with both susceptible and resistant strains when compared with ethambutol at 5.0 micrograms/ml for the conventional method. PMID- 3084553 TI - Comparative antigenic studies of species of Basidiobolus and other medically important fungi. AB - An immunodiffusion technique was used to evaluate the antigenic relationship of various pathogenic and saprobic Basidiobolus spp., Conidiobolus spp., isolates of the order Mucorales, and several other medically important nonzygomycetous fungi. The antiserum to Basidiobolus haptosporus shared two lines of identity, designated inner (N) and outer (Y), when tested against exoantigens of known strains of B. haptosporus and Basidiobolus ranarum as well as exoantigens of a human Nigerian isolate and several wild isolates tentatively identified in B. ranarum. Both bands were heat stable at 56 degrees C for 30 min. Exoantigens of strains of Basidiobolus meristosporus, Basidiobolus microsporus, Conidiobolus incongruus, Conidiobolus coronatus, and other wild isolates of Basidiobolus spp. tested formed only the N immunoprecipitin band. Exoantigens of 10 isolates from other taxa did not produce any cross-reactive precipitin line. B. meristosporus antiserum that was tested against exoantigens of Basidiobolus spp. and of Conidiobolus spp. developed only an N band without a Y band. These data suggest that B. haptosporus and B. ranarum are antigenically similar to each other and distinct from B. meristosporus. Basidiobolus spp. and Conidiobolus spp. share a common N immunoprecipitin band, which implies a taxonomic relationship between these two genera. The absence of lines of identity between Basidiobolus spp. and other fungi tested suggests that, antigenically, Basidiobolus is a distinct genus. PMID- 3084554 TI - Analysis of mycolic acid cleavage products and cellular fatty acids of Mycobacterium species by capillary gas chromatography. AB - After growth and experimental conditions were established, the mycolic acid cleavage products, constituent fatty acids, and alcohols of representative strains of Mycobacterium tuberculosis, M. smegmatis, M. fortuitum complex, M. kansasii, M. gordonae, and M. avium complex were determined by capillary gas chromatography. Reproducible cleavage of mycolic acid methyl esters to tetracosanoic (24:0) or hexacosanoic (26:0) acid methyl esters was achieved by heating the sample in a high-temperature muffle furnace. The major constituent fatty acids in all species were hexadecanoic (16:0) and octadecenoic (18:1 omega 9-c, oleic) acids. With the exception of M. gordonae, 10-methyloctadecanoic acid was found in all species; moreover, M. gordonae was the only species tested which contained 2-methyltetradecanoic acid. M. kansasii was characterized by the presence of 2,4-dimethyltetradecanoic acid, M. avium complex by 2-eicosanol, and M. tuberculosis by 26:0 mycolic acid cleavage product. The mycolic acid cleavage product in the other five species tested was 24:0. Although a limited number of strains and species were tested, preliminary results indicate that this gas chromatographic method can be used to characterize mycobacterial cultures by their mycolic acid cleavage products and constituent fatty acid and alcohol content. PMID- 3084555 TI - An outbreak of group B meningococcal disease: tracing the causative strain of Neisseria meningitidis by DNA fingerprinting. AB - Following an outbreak of meningococcal disease in three schoolchildren in a small community in northern Norway, DNA fingerprinting, serotyping with monoclonal antibodies, serogrouping, and sulfonamide sensitivity testing were applied for characterization and tracing of the causative agent. The three case isolates were genomically indistinguishable, sulfonamide-resistant, serogroup B, serotype 15 meningococci. Throat specimens were collected from 552 healthy contacts, including all children below age 17 and their parents. Among the 36 carrier isolates (carrier rate, 6.5%) 13 showed DNA fingerprints identical, or almost identical, to the index pattern. All of these 13 isolates were sulfonamide resistant, 12 were of serotype 15, and 8 were of polysaccharide serogroup B (5 were nongroupable). These closely related isolates were almost exclusively recovered from schoolchildren of 2 of 15 small villages, one of which included the homes of two of the patients. The remaining 23 carrier isolates were nonresistant, non-type 15 meningococci of widely differing DNA restriction patterns. Our results confirm that DNA fingerprinting has potential as an efficient tool in practical meningococcal epidemiology. PMID- 3084556 TI - Identification of mycoplasma colonies by immunobinding. AB - An immunobinding assay was developed to identify mycoplasma colonies on agar in pure and mixed cultures. Mycoplasma colonies on agar were transferred to nitrocellulose. The nitrocellulose was treated with specific rabbit antisera against mycoplasmas, peroxidase-conjugated goat anti-rabbit immunoglobulin G, 4 chloro-1-naphthol, and H2O2. Purple developed in the presence of specific reactions. The procedure was superior to epifluorescence. PMID- 3084557 TI - Analysis by coagglutination of the distribution of a 24,000-dalton surface protein in Yersinia isolates. AB - The presence of a 24,000-dalton surface protein in 215 isolates of Yersinia enterocolitica and related species was examined. By coagglutination with the specific antiserum, a 100% correlation with the pathogenic biogroups was found. Thus, this method is useful for the rapid screening of potential pathogenic Y. enterocolitica isolates. PMID- 3084558 TI - Invasive methods of somatosensory evoked potential monitoring. PMID- 3084559 TI - Immunoglobulin M antibodies present in the acute phase of Kawasaki syndrome lyse cultured vascular endothelial cells stimulated by gamma interferon. AB - Kawasaki syndrome (KS) is characterized by diffuse vasculitis and marked T cell and B cell activation. In this study, sera from 16 patients with acute KS, 15 patients in the convalescent phase of KS, and 19 age-matched controls were assessed for complement dependent cytotoxic activity against 111In-labeled human umbilical vein endothelial (HUVE) cells, Neither sera from patients with KS nor sera from controls had cytotoxic effects on HUVE cells cultivated under standard conditions. Since activated T cells such as those present in acute KS secrete gamma interferon (gamma-IFN), we also examined the effects of sera from acute KS on HUVE cells preincubated with gamma-IFN. We report here that immunoglobulin M (IgM) antibodies in sera from patients with acute KS cause significant (P less than 0.01) killing of gamma-IFN-treated HUVE cells. Pretreatment with interleukin 2, gamma-IFN, or beta-IFN failed to render HUVE susceptible to lysis with acute KS sera. The observed effects were not mediated via immune complexes. The cytotoxic antibodies in acute KS seem to be directed against inducible monomorphic antigenic determinants present on gamma-IFN-treated HUVE cells but not on control or gamma-IFN treated autologous human dermal fibroblasts (HDF). Similarly, acute KS sera also induced lysis of gamma-IFN-treated human saphenous vein endothelial (HSVE) cells but not gamma-IFN treated human saphenous vein smooth muscle (HSVSM) cells. Since gamma-IFN induces the same level of class I and class II major histocompatibility complex (MHC) antigen expression on HDF, HUVE, HSVE, and HSVSM cells, our results suggest that the anti-endothelial cell antibodies in acute KS are directed to gamma-IFN-inducible molecules other than MHC determinants. These observations are further substantiated by the failure of human B cells or monocytes to absorb the anti-endothelial cell activity. Since most vasculitides, including acute KS, are characterized both by marked immune activation and the secretion of lymphokines, antibodies directed to gamma-IFN inducible endothelial cell antigens may represent a general mechanism for vascular injury. PMID- 3084560 TI - Bacterial lipoteichoic acid sensitizes host cells for destruction by autologous complement. AB - Lipoteichoic acids (LTA) released by gram-positive bacteria can spontaneously bind to mammalian cell surfaces. In the present study, erythrocytes (E) sensitized with pneumococcal LTA (LTA-E) were used as a model system to determine if LTA could render host cells susceptible to damage by autologous complement. Complement (C)-mediated lysis of LTA-E from normal rats and normal humans occurred when these cells were incubated in their respective autologous sera in vitro. In addition, when LTA-E from a C2-deficient human and from C4-deficient guinea pigs were incubated in their autologous sera, there was significant lysis in vitro, demonstrating a role for the alternative pathway. The in vivo survival of 51Cr-labeled autologous LTA-E was also studied. Only 2.9% of autologous LTA-E remained in the circulation of normal rats after 90 min. In contrast, 31.2% of autologous LTA-E remained in the circulation of rats depleted of C3. Intravascular hemolysis accounted for the clearance of LTA-E in the normal rats, whereas liver sequestration was responsible for clearance in the C3-depleted rats. These results demonstrate that LTA can render the host's cells susceptible to damage by its own complement system, establishing this as a possible mechanism of tissue damage in natural bacterial infections. PMID- 3084561 TI - Specific binding of antigen onto human T lymphocytes. AB - Human T lymphocytes sensitized to Candida albicans (CA) were shown to proliferate in cultures induced with mannan, a ramified polysaccharide extracted from the cell well of CA. We presently describe that, when we used strongly labeled [3H]mannan, antigen-specific T blast cells were able to bind the labeled mannan on their membrane. The observations that irrelevant blast cells did not bind [3H]mannan, and that mannan-specific blast cells did not bind tritiated pneumococcal polysaccharide SIII, indicate the specificity of mannan binding. Mannan binding was reversible and saturable. Mannan binding on T blast cells was inhibited by preincubation with monoclonal antibodies to T3 but not to other T cell-related molecules. The characteristics of this receptor suggest its identity with the T cell receptor for antigen. The direct binding of mannan could be either due to a cross-linking of the receptor by multivalent mannan or to a recognition of mannan in association with HLA-DQ molecules, as suggested by partial blocking of mannan binding using anti-HLA-DQ monoclonal antibodies. PMID- 3084562 TI - Mechanisms of lymphocyte adhesion to human vascular endothelial cells in culture. T lymphocyte adhesion to endothelial cells through endothelial HLA-DR antigens induced by gamma interferon. AB - The effects of interferons (IFNs) on lymphocyte adhesion to cultured human vascular endothelial cells (EC) were investigated using an in vitro assay. Endothelial cells obtained from umbilical vein were first cultured at a low density with a conditioned medium (CM) from 12-O-tetra decanoylphorbol 13-acetate concanavalin A (TPA-Con A) stimulated human peripheral blood lymphocytes (PBL), or with recombinant (r) gamma interferon (IFN-gamma) or r alpha interferon (IFN alpha), and then were incubated with freshly isolated PBL. Natural IFN-gamma in the TPA-Con A CM and rIFN-gamma (12.5-500 U/ml) induced major histocompatibility complex-class II antigens (HLA-DR, HLA-DP, and HLA-DQ) and significant lymphocyte adhesion to the EC, whereas rIFN-alpha did not. The lymphocyte adhesion to the EC and the expression of DR antigens on the EC were well correlated in terms of both kinetics and the dose-response pattern of rIFN-gamma. When EC expressing I region associated (Ia) antigen were preincubated with monoclonal anti-DR antibody before the addition of lymphocytes, the lymphocyte adhesion was significantly inhibited in both allogeneic and syngeneic combinations, whereas anti-HLA-DP, anti-HLA-DQ, and anti-HLA-ABC antibodies did not inhibit the binding at all. Cell fractionation experiments indicated that the majority of lymphocytes adhering to Ia-expressed EC were Leu-3+ T cells, whose binding was again almost completely inhibited by anti-DR antibody. Moreover, anti-Leu-3a, but not anti-Leu-2a, antibody effectively inhibited the T cell adhesion to the EC. These results strongly suggest that the interaction of the Leu-3(T4) receptor of T cells with IFN-gamma-induced DR antigens on EC plays a central role in the selective adhesion of Leu-3+ T cell to EC. PMID- 3084563 TI - 1,25 Dihydroxyvitamin D increases hepatocyte cytosolic calcium levels. A potential regulator of vitamin D-25-hydroxylase. AB - 1,25 dihydroxyvitamin D (1,25(OH)2D) has been demonstrated to inhibit hepatic 25 hydroxyvitamin D (25 OHD) production. Changes in cytosolic calcium have been shown to regulate cellular processes. Using the fluorescent dye Quin 2, we have investigated the effects of 1,25(OH)2D and 24,25(OH)2D on cytosolic calcium levels in hepatocytes. 1,25(OH)2D exposure for 5 min increases cytosolic calcium levels by 24% at a concentration of 100 pg/ml, 39% at a concentration of 1 ng/ml, and 50% at a concentration of 2 ng/ml. The latter increment occurs in both the presence and absence of extracellular calcium, indicating that 1,25(OH)2D is mobilizing intracellular calcium pools. 24,25(OH)2D, 10 ng/ml, does not increase cytosolic calcium levels while the calcium ionophore A23187, 3 microM, increases levels by 52%. Calcium inhibits hepatic 25 OHD synthesis in liver homogenates in a dose-dependent fashion, which can be prevented by chelation of calcium with EGTA. 1,25(OH)2D and A23187 decrease hepatocyte 25 OHD synthesis. The inhibitory effect of A23187 can be prevented by chelation of extracellular calcium. The data demonstrate that 1,25(OH)2D increases hepatocyte cytosolic calcium, and that these increments in cytosolic calcium may regulate some of the hepatic actions of the vitamin D metabolite. PMID- 3084564 TI - Regulation of net bicarbonate transport in rabbit cortical collecting tubule by peritubular pH, carbon dioxide tension, and bicarbonate concentration. AB - The effects of changes in peritubular pH, carbon dioxide tension (PCO2), and HCO3 concentration on net HCO3- transport was examined in in vitro perfused cortical collecting tubules (CCTs) from unpretreated New Zealand white rabbits. Lowering peritubular HCO3- concentration and pH by reciprocal replacement of HCO3- with Cl , significantly stimulated net HCO3- absorption. Lowering peritubular HCO3- concentration and pH, by substitution of HCO3- with gluconate, while keeping Cl- concentration constant, also stimulated net HCO3- absorption. Raising peritubular HCO3- concentration and pH, by reciprocal replacement of Cl- with HCO3-, inhibited net HCO3- absorption (or stimulated net HCO3- secretion). When the tubule was cooled, raising peritubular HCO3- concentration had no effect on net HCO3- transport, suggesting these results are not due to the passive flux of HCO3 down its concentration gradient. The effect of changes in ambient PCO2 on net HCO3- transport were also studied. Increasing the ambient PCO2 from 40 mmHg to either 80 or 120 mmHg, allowing pH to fall, had no effect on net HCO3- transport. Similarly, lowering ambient PCO2 to 14 mmHg had no effect on net HCO3- transport. Simultaneously increasing peritubular HCO3- concentration and PCO2, without accompanying changes in peritubular pH, i.e., isohydric changes, stimulated net HCO3- secretion to the same degree as nonisohydric increases in peritubular HCO3- concentration. Likewise, isohydric lowering of peritubular HCO3- concentration and PCO2 stimulated net HCO3- absorption. We conclude that: acute changes in peritubular HCO3- concentration regulate acidification in the CCT and these effects are mediated by a transcellular process; acute changes in ambient PCO2 within the physiologic range have no effect on HCO3- transport in the in vitro perfused CCT; and acute in vitro regulation of CCT acidification is independent of peritubular pH. PMID- 3084565 TI - Evaluation of three methods for estimating fetal weight. AB - Three ultrasonic methods for estimating fetal weight (Campbell, Warsof, and Shepard) were compared in 124 singleton pregnancies. Fetal abdominal circumference was obtained by use of a map measurer and from diameter measurements and the equation for the circumference of a circle. Campbell's formula for estimating fetal weight was superior between 2,000 and 4,000 g, whereas Shepard's method was slightly better below 2,000 g and over 4,000 g. Hence, varied fetal anthropometric characteristics make it mandatory that several methods be evaluated by each institution before one is selected. With the methods of Campbell and Shepard, use of diameter measurements and the equation for the circumference of a circle resulted in a more accurate estimated fetal weight than when a map measurer was used. PMID- 3084566 TI - Ultrasonographic findings in the livers of patients with lepromatous leprosy. AB - Abdominal ultrasonography, including assessment of the liver, spleen, pancreas, great abdominal vessels, and kidneys, was carried out in seven patients with lepromatous leprosy, six patients with tuberculoid leprosy, and 32 healthy Congolese controls. Abnormal ultrasound findings were predominantly detected in the livers of patients with lepromatous leprosy and included an inhomogeneous echo texture of the hepatic parenchyma in all cases. Furthermore, six patients revealed echo-dense, partly irregular areas up to 1.5 cm X 3 cm in size distributed throughout the liver. These were associated with shadowing and were considered to contain calcium. No abnormal findings were encountered in controls or in patients with tuberculoid leprosy except for one patient with tuberculoid leprosy who had a rounded caudal liver edge. The sizes and volumes of liver, spleen, and kidneys were not different in the three groups. PMID- 3084567 TI - Ultrasound measurement of the fetal cerebral ventricles: a prospective, consecutive study. AB - Real-time ultrasound was used in 654 consecutive pregnancies to obtain standard growth parameters for the fetal brain. Measurement of the width of the lateral ventricle (LVW) and hemisphere and their relationships to menstrual age, biparietal diameter, and birth weight were determined. The growth of the LVW was to a great extent independent of birth weight but dependent on menstrual age. Thirteen fetuses with a single ventricular width measurements exceeding +2 SD from the mean were separately evaluated, and all but one case were found to be normal. PMID- 3084568 TI - Diagnosis of leukemic relapse in the pelvic soft tissues of juvenile females. AB - Five females with childhood acute lymphocytic leukemia whose disease relapsed in the pelvis were studied. In all five patients, relapse occurred late in the disease process, and all patients had been in complete continuous remission before relapse. Intravenous pyelogram and barium enema revealed hydronephrosis or a mass effect on the bladder or rectosigmoid colon. In three patients, sonography established the presence of a clinically palpable mass with involvement of the uterus, ovaries, and pelvic side walls. In one patient there was infiltration of the bladder and in another, infiltration of the appendix, both confirmed by biopsy. PMID- 3084569 TI - Antenatal sonographic diagnosis of complicated ovarian cysts. PMID- 3084570 TI - Ultrasonic demonstration of superior mesenteric and splenoportal venous thrombosis. PMID- 3084571 TI - Nephrolithiasis and cholelithiasis in a premature infant. PMID- 3084572 TI - Early second-trimester sonographic diagnosis of thoracopagus twins. PMID- 3084573 TI - Detailed analysis of aortic valve endocarditis: comparison of precordial, esophageal and epicardial two-dimensional echocardiography with surgical findings. PMID- 3084574 TI - Sonographic diagnosis of seminal vesicle cysts. PMID- 3084575 TI - Antenatal detection of hepatic cyst. PMID- 3084576 TI - Primary lymphoma of the ascending colon: sonographic demonstration. PMID- 3084577 TI - Prenatal ultrasonographic diagnosis of fetal adrenal neuroblastoma. PMID- 3084578 TI - Ultrasound appearance of particulate matter in amniotic cavity: vernix or meconium? PMID- 3084579 TI - Amebic liver abscess: sonographic diagnosis and management. AB - Over a period of 3 years, 68 intrahepatic abscesses in 48 patients were detected by ultrasonography at our institution in New Delhi, India. Our experiences with the sonography and management of this entity are presented. Multiple abscesses were present in 14 patients; the rest had a single abscess. The most common location was the right lobe of the liver. The sonographic morphology of the abscess was analyzed in terms of the echo pattern of the wall and contents of the abscess. These were later correlated with the duration of illness. An attempt was made to assess healing and thereby the age of the abscess. Follow-up ultrasound scans indicated that the change in sonographic appearance lags behind clinical improvement by a considerable period of time. PMID- 3084580 TI - Tolerance intervals for standards in ultrasound measurements: determination of BPD standards. AB - Standards for the relationship between BPD and gestational age are used for the assessment of fetal size. We measured the BPD in 310 women with exact gestational age in a cross-sectional study. Two types of BPD charts were constructed based on tolerance intervals: directly from measurements and after model fitting. We found that the tolerance intervals based on the model are smoother and narrower than those achieved by direct determinations. The fit, advantages, and prospects of the model are discussed. PMID- 3084581 TI - Pseudoepidural reverberation artifact: a common ultrasound artifact in fetal cranium. AB - High-intensity reverberation artifacts frequently occur within the fetal cranium during obstetric ultrasound examinations. One hundred ninety-six static ultrasonograms obtained from 100 consecutive obstetric patients were reviewed to determine the incidence, shape, and location of high-intensity reverberation artifacts within the fetal head. Such artifacts occurred in one-third of the fetuses examined. The most common appearance was an arc-shaped artifact that occurred most frequently in the fetal hemicranium farthest from the maternal skin surface. Such an artifact can mimic epidural fluid collections and cause confusion for examiners not familiar with this finding. A discussion of this "pseudoepidural" artifact, its cause, and ways of excluding underlying intracranial pathology is presented. PMID- 3084583 TI - Further studies on ultrasonic properties of blood clots. AB - Two-dimensional echocardiography has been found to be an effective clinical tool in diagnosing intracardiac thrombi. Misdiagnosis may, however, still frequently occur because of the difficulty in differentiating the thrombi from other intracavitary masses based only on the echographic appearance of these structures. Ultrasonic tissue characterization techniques have been used in attempts to minimize this diagnostic uncertainty. Previously, we have shown that all ultrasonic parameters of blood, including ultrasonic backscatter, a quantitative measure of echogenicity, at 7.5 MHz increase rapidly following clotting. In this article, we report recent results on the measurements of attenuation and backscatter of thrombi as a function of time following clotting over the frequency range of 3 MHz to 8 MHz. These results indicate that ultrasonic backscatter from thrombi 12 h old is at least 18 dB higher than that of unclotted blood over the frequency range of 3 MHz to 8 MHz, and the slope of the attenuation coefficient is increased to 0.43 dB/cm-MHz. Comparison with the backscatter of bovine myocardium shows that the myocardium is more echogenic than fresh thrombi and is less echogenic than thrombi 12 to 24 h old. Similar results were also obtained for integrated backscatter measurements over the same frequency range. PMID- 3084582 TI - A pictorial essay of pelvic and abdominal masses seen during pregnancy. AB - Since the advent of ultrasound, pelvic and abdominal masses occurring with pregnancy are being recognized more frequently and at earlier stages of gestation. The precise sonographic definition of the size and location of a mass is important for determining route of delivery or surgical approach during laparotomy and cesarean sections. We hope to illustrate that a variety of etiologies need to be considered, and although it is not often possible to make a histologic diagnosis on the basis of ultrasound finding alone, the integration of imaging information with other clinical data can be helpful in narrowing the differential diagnostic possibilities. PMID- 3084584 TI - Removal of air from liver specimens via vacuum. AB - Fresh liver specimens have been ultrasonically imaged in vitro in order to evaluate specimen air content before the acquisition of ultrasonic waveform data for tissue characterization studies. It was found necessary to expose liver slices to vacuum for about 16 h in order to remove enough air to acquire waveform data from air-free regions of interest in these slices. Larger portions of liver, and whole liver, were found to retain large amounts of air even after 16 h of exposure to vacuum. PMID- 3084586 TI - Ultrasonic characteristics of tumefactive biliary sludge: a thixotropic phenomenon. PMID- 3084585 TI - Ultrasound diagnosis of renal calcification in infants on chronic furosemide therapy. AB - We describe seven infants who developed renal calcification and bone demineralization following furosemide therapy with average daily doses of as little as 0.75 mg/kg per day. Renal calcifications were present in all seven cases and were more readily detected with ultrasonography than with plain films. Renal calculi were seen in four patients, sonographically demonstrated as echogenic foci in the dependent portion of the collecting system, usually accompanied by acoustic shadowing. One patient developed nephrocalcinosis, sonographically observed as echogenic medullary pyramids plus punctate, shadowing parenchymal calcifications. In two patients the location of the calcification could not be determined. PMID- 3084587 TI - Congenital chloridorrhea: antenatal ultrasonographic appearance. PMID- 3084588 TI - Echocardiographic evidence of mediastinal lymph node enlargement in T-acute lymphoblastic leukemia with acute pericarditis. PMID- 3084589 TI - Ultrasonic appearance of the liver in hepatic venous outflow obstruction (Budd Chiari syndrome): a case of pseudohepatic infarct associated with Behcet's disease. PMID- 3084590 TI - Antenatal ultrasound diagnosis of an intracranial neoplasm (craniopharyngioma). PMID- 3084591 TI - Spontaneous resolution of unilateral hematometra in a patient with bicornuate uterus: sonographic findings. PMID- 3084592 TI - Ultrasound demonstration of a benign mesothelioma of tunica vaginalis testis. PMID- 3084593 TI - Sonographic features of milk of calcium cholecystitis. PMID- 3084594 TI - Biventricular thrombus formation in association with acute myocardial infarction: diagnosis by two-dimensional echocardiography. PMID- 3084595 TI - Small hyperechoic nodules of the renal parenchyma. PMID- 3084596 TI - Benign and malignant (B cell) focal lymphoid aggregates in bone marrow trephines shown by means of an immunogold-silver technique. AB - A series of 36 iliac crest trephines, previously shown to contain follicular lymphoid aggregates, were examined using the immunogold-silver staining technique. This showed the presence of kappa and lambda surface immunoglobulin in paraffin sections of the specimens. In those trephines from patients known to be suffering from chronic lymphocytic leukaemia there was distinct monoclonality for expression of either kappa or lambda surface light chains on the lymphocyte cell surfaces in and usually between the lymphoid nodules. In specimens containing aggregates, which had previously been diagnosed as benign on morphological and clinical criteria, both kappa and lambda chains were expressed. A small number of trephines containing aggregates of uncertain nature were also examined; these all showed monoclonal expression of either kappa or lambda chains and subsequently proved to be clinically malignant. Dendritic reticulum cells, shown by staining for surface immunoglobulin, were observed only in benign aggregates. PMID- 3084597 TI - Absence of tachyphylaxis in gastric acid secretion during pentagastrin infusion. AB - Tachyphylaxis to stimulation of gastric juice secretion during intravenous pentagastrin (PG) infusion has been reported in animal studies. We assessed the course of gastric response to PG 2 micrograms/kg/hr over eight hours in eight healthy subjects. Peak H+, pepsin, and volume secretions occurred during the second half hour of stimulation. Peak H+ output was 11.6 +/- 1.3 mmol/0.5 hr or 7.6 +/- 0.8% of the total eight-hour secretion. During subsequent half-hour collection intervals, there was no significant decline in response, and the average output was 10.3 +/- 0.4 mmol/0.5 hr (6.5 +/- 0.1%). Peak pepsin and volume secretions were respectively 10.0 +/- 1.4% (74.8 +/- 11.6 mg/0.5 hr) and 8.8 +/- 1.1% (146.3 +/- 17.4 mL/0.5 hr) of the total eight-hour secretion. Although there was a significant decline in pepsin and volume response subsequent to the peak output, the decline was not continuous, and pepsin and volume secretions were maintained, respectively, at 6.0 +/- 0.2% (46.1 +/- 2.5 mg/0.5 hr) and 6.2 +/- 0.1% (107.5 +/- 3.0 mL/0.5 hr) of the total eight-hour secretion. Our study did not demonstrate any tachyphylaxis in H+ response to continuous PG stimulation. This model appears to be a valid tool for the assessment of histamine-H2 antagonist effects on stimulated gastric juice secretion over 8 hours in humans. PMID- 3084598 TI - An inverse relationship between mania and obsessive-compulsive disorder: a case report. PMID- 3084600 TI - Chemotherapy of East Coast fever: the long term weight changes, carrier state and disease manifestations of parvaquone treated cattle. AB - The weight changes, carrier state and nature of chronic disease in cattle following infection with five isolates of Theileria parva and treatment with parvaquone were studied over an 18 month period while the cattle were maintained on normal management under strict tick control. Cattle infected with the T.p. parva Pugu II isolate gained weight similarly to uninfected control cattle and did not develop a detectable carrier state or show chronic disease. The cattle in the 4 other isolate groups regained the weight lost during the initial infection more slowly, then gained weight in parallel to the control cattle. Transmission of infection through ticks was achieved consistently from the T.p. parva Mbita I and Entebbe II isolate infections and intermittently from the T.p. lawrencei Mara II and Manyara infections. Infections were transmitted from cattle which had neither a detectable parasitaemia nor an antitheilerial antibody titre. Persistent macroschizont parasitoses were detected with the T.p. parva Entebbe II and the two T.p. lawrencei infections. The histopathology of the chronic disease lesions is described and the importance of the carrier state discussed. PMID- 3084599 TI - Studies on the evolution of multiple somatosensory representations in primates: the organization of anterior parietal cortex in the New World Callitrichid, Saguinus. AB - Because members of the New World family, Callithricidae, are generally regarded as the most primitive of monkeys, we studied the organization of somatosensory cortex in the tamarin (Saguinus) in hopes of better understanding differences in the organization of anterior parietal cortex in primates and how these differences relate to phylogeny. In most prosimian primates only one complete representation of cutaneous receptors has been found in the region of primary cortex, S-I, while in all Old and New World monkeys studied to date, two cutaneous representations exist in distinct architectonic fields, areas 3b and 1. In detailed microelectrode mapping studies in anesthetized tamarins, only one complete representation responsive to low-threshold cutaneous stimulation was evident in the S-I region. This topographic representation was in a parietal koniocortical field that architectonically resembles area 3b of other monkeys, and the general somatotopic organization of the field was similar to that of area 3b of other monkeys. Cortex rostral to the single representation was generally unresponsive to somatosensory stimuli, or required more intense stimulation for neural activation. Cortex caudal to the representation, in the region of area 1 of other monkeys, was generally either unresponsive or responded to only high threshold stimulation, although some recording sites were activated by low threshold tactile stimulation. The present evidence, together with that from previous studies, suggests that the single, complete body surface representation in Saguinus is homologous to the S-I representation found in some prosimians (Galago, Perodicticus) and the area 3b cutaneous representation found in New World Cebidae (Aotus, Saimiri, and Cebus) and Old World Macaca. Cortex rostral to S-I in Saguinus has the appearance of areas 3a and 4 of other primates. The cortex caudal to S-I in Saguinus, while resembling area 1 in some ways, does not have all of the features of area 1 of other monkeys. In particular, the field was not easily activated by low-threshold cutaneous stimuli, as area 1 is in other monkeys, and therefore a second cutaneous representation of all body parts was not demonstrated. Thus, cortex in the expected location of area 1 of Saguinus was not as responsive as area 1 of other monkeys, and it somewhat resembled the high threshold fringe zones found caudal to S-I in anesthetized prosimians and some nonprimates. The results raise the possibility that the area 1 cutaneous representation that is characteristic of other New World monkeys and Old World monkeys evolved from a less responsive precursor along the caudal border of S-I in early monkeys. PMID- 3084601 TI - Effect of chronic growth hormone treatment on responses to epinephrine and thyrotropin-releasing hormone in lactating cows. AB - Bovine growth hormone was administered to four Holstein cows (late lactation) in a Latin square. Treatments were 1) control, subcutaneous injection of placebo, 2) subcutaneous injection of 25 IU growth hormone on alternate days, 3) daily subcutaneous injection of 25 IU growth hormone, and 4) continuous subcutaneous infusion of 25 IU/d growth hormone. Intravenous challenges of epinephrine and thyrotropin-releasing hormone were administered separately on the 1st d after a 12-d interval of growth hormone treatment. Baseline concentrations of nonesterified fatty acids in plasma were not affected by growth hormone treatment. However, release of nonesterified fatty acids to epinephrine challenge was positively related to amount of growth hormone in plasma during treatment and was correlated with milk fat yield and milk energy secretion. Growth hormone release following thyrotropin-releasing hormone was negatively related to amount of growth hormone in plasma during treatment. Release of prolactin to thyrotropin releasing hormone challenge was not related to average daily dose of exogenous growth hormone. The galactopoeitic action of growth hormone may be partly attributable to its effects on responsiveness of adipose tissue to a lipolytic stimulus but apparently is not associated with changes of pituitary sensitivity to thyrotropin-releasing hormone. Results are consistent with growth hormone functioning as a homeorhetic control of nutrient partitioning. PMID- 3084602 TI - Growth hormone-releasing factor stimulates milk production and sustains growth hormone release in Holstein cows. AB - Serum growth hormone was determined in lactating cows following repeated intravenous injections of growth hormone-releasing factor. A given dose was injected every 4 h for 24 h in a 4 (cow) X 4 (d) Latin square. Growth hormone increased similarly above controls after 10, 20, or 40 micrograms releasing factor/100 kg body weight. In another experiment the effects on lactational performance and growth hormone responses of cows to repeated injections of releasing factor for 10 d were determined in a 2 (cow) X 2 (period) Latin square crossover. Administration of 20 micrograms releasing factor/100 kg body weight to 16 Holstein cows (lactating 4.5 to 7.5 mo) every 4-h for 10 d increased milk yield from 25.4 to 27.7 kg/d and increased total fat, protein, and lactose 11% above controls. Releasing factor did not affect milk composition or feed intake. Peak growth hormone response to releasing factor was similar between d 1 (19.9 ng/ml) and 10 (24.4 ng/ml). Exogenous growth hormone-releasing factor administered to lactating Holstein cows at the doses tested: 1) increases growth hormone consistently, although the response is not dose dependent, 2) is galactopoietic, 3) causes an apparent increase in feed to milk conversion, and 4) increases growth hormone to at least the same magnitude on d 10 as on d 1. PMID- 3084603 TI - Evidence for impaired metabolism in liver during induced lactation ketosis of dairy cows. AB - Ketosis was induced in four lactating dairy cows at an average of 36 d postpartum and 24 d after initiation of a protocol for inducing ketosis. Liver and adipose biopsies were taken at five stages; once prepartal, once early postpartal, once during an induction protocol, once during ketosis, and once during recovery after treatment of ketosis. At each stage, in vitro estimates were made of capacities of liver slices for gluconeogenesis, fatty acid oxidation, and ketogenesis and of capacities of adipose tissue slices for lipogenesis and lipolysis. There were no significant differences for any metabolic capacity between prepartal and early postpartal stages; however, a significant decrease in hepatic metabolic activity was associated with ketosis. Gluconeogenic rates from all substrates tested were decreased significantly during ketosis, and similar decreases were measured for oxidation of gluconeogenic substrates and fatty acids. Treatment of ketosis resulted in complete recovery from impairments of metabolism in liver. Results suggest that a prolonged energy deficit, plus a major influx of ketone precursors, is accompanied by eventual hepatic impairment, that clinical ketosis is associated with this impairment, and that the impairment is reversed by effective treatment of ketosis. PMID- 3084604 TI - Differential response to hyperventilation in panic disorder and generalized anxiety disorder. PMID- 3084605 TI - Total parenteral nutrition in patients with insulin-requiring diabetes mellitus. AB - The clinical course of 24 patients with insulin-requiring diabetes mellitus who had received total parenteral nutrition (TPN) was retrospectively analyzed. Routine nutritional assessment disclosed significant depression of anthropometric indices and secretory protein levels in patients with chronic renal failure complicating juvenile onset diabetes mellitus (JODM). Biochemical complications including hypo- or hyperglycemia were significantly more frequent (p less than 0.001) in JODM than in maturity-onset diabetes and found to a lesser degree in patients with renal failure. The catheter infection rate was substantially higher (17%) than usually encountered in TPN therapy. Positive nitrogen balance was achieved in the majority of patients with an average 84% and 92% of estimated protein and caloric requirements being provided. Close monitoring and a protocol of infusion plus supplemental subcutaneous regular insulin was useful in providing adequate TPN safely to these high-risk patients. PMID- 3084606 TI - Immunoregulatory disorders associated with hereditary angioedema. I. Clinical manifestations of autoimmune disease. AB - Occasional reports have appeared linking hereditary angioedema (HAE) with autoimmune diseases. We have systematically evaluated 157 patients for manifestations of autoimmunity. Nineteen of these patients (12%) had clinical immunoregulatory diseases including glomerulonephritis (five patients), Sjogren's syndrome (three), inflammatory bowel disease (three), thyroiditis (two), systemic lupus erythematosus (one), drug-induced lupus (one), rheumatoid arthritis (one), juvenile rheumatoid arthritis with IgA deficiency (one), incipient pernicious anemia (one), and sicca syndrome (one). All eight patients with HAE who developed an autoimmune disease with a known human histocompatibility antigen association developed a disease associated with their histocompatibility antigen haplotype (p = 0.014). Although only four patients developed Sjogren's syndrome or sicca syndrome, an additional nine manifested part of the sicca complex. We also found patients with HAE with features suggestive of an immune-based abnormality. These features included idiopathic pancreatitis (three patients), Raynaud's disease (two), partial lipodystrophy (one), chronic chorioretinitis (one), and alopecia universalis (one). PMID- 3084607 TI - Lithium-resistant adolescent mania. PMID- 3084608 TI - Nutrition guidelines for burned patients. AB - Among all hospitalized patients, burned patients have been shown to have the greatest increase in metabolic demand. However, the temptation to overfeed those patients must be recognized, as that practice may lead to increased morbidity. Care must be taken to provide an appropriate nutritional regimen in order to minimize protein catabolism and to promote wound healing. Several formulas for calculating energy and protein needs for burned patients have been reviewed for this article, along with guidelines for estimating other nutrients for such patients. Methods for providing nutrition therapy depend on many factors, such as extent and degree of injury and gastrointestinal function. The feeding methods most commonly used are parenteral (peripheral and central venous alimentation) and enteral (oral and naso-gastric tube feeding). Guidelines for using both parenteral and enteral feedings are discussed, as well as reliable methods for evaluating the nutrition assessment of the burned patient. It must be noted that standard assessment parameters are often unreliable, and their limitations are also addressed. In addition, several new parameters are introduced, including compliance with caloric goal, corrected weight change, and prediction of total urinary nitrogen to be used to calculate nitrogen balance. PMID- 3084609 TI - Specialized formulas for enteral nutrition support. AB - Enteral or tube feeding is the standard nutritional support modality for patients with a functioning gastrointestinal tract. Expanding knowledge of the role of nutrients in disease has prompted the development of specialized nutrients for patients with specific diseases. Selection of the appropriate formula is critical in maximizing the response to nutrition therapy. Knowledge of related research and the underlying disease process are factors in the selection of appropriate formulas for specialized enteral nutrition support. Careful monitoring of the nutritional and metabolic processes associated with specific diseases is the key to the successful use of the formulas. PMID- 3084610 TI - Correlation of pressure sores and nutritional status. AB - As life expectancy increases, so do the problems of the elderly population. One major problem is that of protein calorie malnutrition; another is the susceptibility of this population to pressure sores. The purpose of this study was to determine if a correlation exists between deteriorating nutritional status and the development of pressure sores. The nutritional status of 232 nursing home patients (mean age 72.9 +/- 12 years) was determined using biochemical and anthropometric measurements. Overall, the incidence of some degree of malnutrition was 59%. Seventeen of the patients were found to have pressure sores and were all malnourished. When classified as mild, moderate, or severe malnutrition, the patients with pressure sores were in the severe group. There was a significant difference (P less than .001) between the nutritional status of pressure sore patients and the malnourished patients. It appears that the development of pressure sores correlates with nutritional deficiencies. The authors' findings suggest a need for more aggressive nutritional support in the elderly, especially those with pressure sores. PMID- 3084611 TI - Age and the hematopoietic system. PMID- 3084612 TI - Acquired inhibitor to factor VIII in a nonhemophiliac patient. PMID- 3084613 TI - Measurement of the deposition and clearance of inhaled radiolabeled particles from rat lungs. AB - Immediately after a 20 min nose only exposure to 51Cr labeled polystyrene latex microspheres (1.4 MMAD, geometric standard deviation = 1.3, 2 micrograms m-3), 23% of the measured radioactivity was within the trachea-lungs of the exposed rats, 37% was within the gastrointestinal tract, 10% was within the defurred head, and 30% was on the fur. One hour after deposition these percentages had changed to 20, 64, 5 and 11%, respectively. As a result of this non-pulmonary particle load transiting the esophagus, external thoracic radioactivity measurements did not accurately reflect excised lung measurements until 30 h post deposition. Consequently, it was necessary to combine excised lung ratioactivity data (0-30 h post deposition) with serial external thoracic measurements (30-934 h post-deposition) to measure the clearance of these microspheres. Use of an annulus shaped detector sufficiently increased sensitivity to allow measurements to be made through at least 934 h post-deposition. The lung radioactivity retention curve was biexponential with half times of 34.3 +/- 2.3 and 963 +/- 107 h. Simultaneous exposures to 5% CO2 increased deposition by 40% but failed to reduce deposition inhomogeneity and test variability. PMID- 3084614 TI - Effects of hypoxia, hypercapnia and acidemia on vagal action at the heart in the dog. PMID- 3084615 TI - Rapid changes in plasma androgens during insulin withdrawal in male type 1 (insulin-dependent) diabetics. AB - Plasma concentrations of testosterone, androstenedione and dihydrotestosterone were measured in 15 Type 1 (insulin-dependent) diabetics with (n = 8) and without (n = 7) B-cell function during 12 h of insulin withdrawal and compared with those of 8 normal subjects. Before insulin withdrawal no significant difference was found in androgen concentrations between the diabetic and the normal subjects. The normal diurnal profiles, with highest androgen concentrations in the morning before insulin withdrawal (08:00) and lowest concentrations at 20:00 h were maintained in the diabetics. However, testosterone and dihydrotestosterone concentrations were lower in the diabetics after 4 h of insulin withdrawal and remained so throughout the study. The concentrations of androstenedione were not significantly different between diabetics and normal subjects except after 4 h of insulin withdrawal. Despite the patients without B-cell function were more metabolically decompensated from after 4 h of insulin withdrawal compared with patients with B-cell function, no significant differences were found in androgen concentrations between the two groups although a tendency to lower concentrations were seen in the group without B-cell function. PMID- 3084616 TI - Prolactin lowering effect of dihydroergokryptine in rat and in man. AB - The prolactin lowering activity of dihydroergokryptine was investigated both in rats and in humans. The drug was administered orally at the doses of 0.2, 1 and 5 mg/Kg to intact or reserpinized male rats. Nine male adult volunteers were given 300 mg cimetidine iv 90 min after receiving 2, 3 or 4.5 mg of dihydroergokryptine and 3, 4.5 and 6.75 mg of dihydroergocristine or placebo per os in a randomized, cross-over design. Eight young adult males were injected im with 10 mg sulpiride 120 min after randomly receiving dihydroergokryptine 2.5 and 5 mg or placebo in a cross-over manner. Finally, five healthy young women were given dihydroergokryptine 2.5 and 5 mg, bromocriptine 2.5 mg and placebo in a cross over design. Dihydroergokryptine caused a strong, long-lasting, dose-dependent fall of plasma prolactin concentrations in both rats and humans. Moreover, it inhibited the reserpine-induced rise of plasma prolactin in rats, as well as the cimetidine-or sulpiride-induced hyperprolactinemia in humans. Dihydroergokryptine proved twice as potent as dihydroergocristine and about half as potent as bromocriptine. Effective doses of both dihydrogenated ergot alkaloids were much better tolerated than bromocriptine. PMID- 3084618 TI - Impaired adrenergic stimulation of rat parotid cell glucose oxidation during aging: the role of calcium. AB - Adrenergic stimulation of glucose oxidation by epinephrine is reduced by 30 to 40% in isolated rat parotid cell aggregates from aged rats compared with young adults. Such impairment affects both the external calcium dependent and independent components of the response. Age-related differences in glucose oxidation are obliterated if adrenergic receptors are bypassed and stimulation achieved by exposing cells to various concentrations of calcium in the presence of the ionophore, A23187. Thus, impaired calcium mobilization may play, in part, a role in reduced rat parotid adrenergic metabolic responsiveness during aging. PMID- 3084617 TI - Involvement of endogenous gabaergic system in the modulation of gonadotropin secretion in normal cycling women. AB - To investigate whether endogenous GABA participates in the control of gonadotropin secretion during the menstrual cycle, placebo or sodium valproate (DPA), an anticonvulsant drug which enhances endogenous GABA content by blocking GABA degradation, were administered to regularly cycling women both during early follicular and midluteal phase. In a first set of experiments, the effect of DPA administration (400 mg, orally) on basal gonadotropin secretion was evaluated in 13 subjects. During early follicular phase (n = 6), no significant changes in plasma gonadotropin levels were observed after DPA or placebo administration. Conversely, during midluteal phase (n = 7), DPA administration resulted in a significant fall (p less than 0.01) in plasma LH concentrations, with a maximal percent decrease of 41.8 +/- 6.7% after 120 min. No changes in plasma FSH levels were observed. In a second set of experiments, the effect of DPA pretreatment (400 mg, orally) on gonadotropin release stimulated by a pulse of exogenous GnRH (10 micrograms, iv bolus) was studied in 11 subjects. During both follicular (n = 4) and luteal phase (n = 7), DPA did not modify gonadotropin response to GnRH injected 1h after pretreatment. Finally, 8 subjects were submitted to iv injection with 10 micrograms GnRH 2h after pretreatment with DPA (400 mg, orally) or placebo. During both follicular (n = 4) and luteal phase (n = 4), no statistical differences in gonadotropin response to GnRH were found between DPA and placebo pretreatment. These findings demonstrated that during the estrogen progesterone (midluteal) phase of menstrual cycle, endogenous GABA is involved in the inhibitory regulation of LH secretion at a central level. PMID- 3084619 TI - [Chemotherapy in 143 advanced epithelial cancers of the ovary. Experience at the Hotel-Dieu of Quebec and Hopital Saint-Antoine (Paris)]. AB - Results of initial chemotherapy in 143 patients with advanced epithelial ovarian cancer are presented. Twenty-five patients were treated with alkylating agents, their median survival was 13 months and 15% were alive at 4 years. Nineteen received Cyclophosphamide-Methotrexate-5 Fluorouracil with or without Hexamethylmelamine, median survival was 22 months and 4 years survival was 20%. Forty-eight were treated with Adriamycin and Cisplatinum, their objective response rate proven by second-look laparotomy was 54.4% (26.1% complete response), median survival was 23 months and 35% were alive at 4 years. Thirty one received Hexamethylmelamine, 5 Fluorouracil, Adriamycin and Cisplatinum with a median survival of 18 months and 4 years survival of 15%. Twenty had various other chemotherapy regimens, their median survival was only 8 months. Recent advances in the therapy of ovarian carcinoma are also discussed. PMID- 3084620 TI - The competitive effects of health maintenance organizations: another look at the evidence from Hawaii, Rochester, and Minneapolis/St. Paul. AB - There has been much discussion about the potential cost-containing impact of HMOs upon the local medical care market. Three areas have been identified by various observers as experiencing such beneficial effects: Hawaii, after the development of Kaiser in the late 1950s; Rochester, New York, which experienced rapid HMO growth and declining Blue Cross hospital use in the late 1970s; and Minneapolis/St. Paul, which has been the focus of vigorous HMO competition in the last decade. While comprehensive data on health care expenditures are not available, bits of evidence can be pieced together to develop case studies of each area. Careful review of the available data often identifies internal inconsistencies and contradictions, but in none of the three sites is there a reduction in hospital use that is most plausibly attributed to HMO competition. Instead, the reported reductions are in each case attributable to other factors- including biases in data, long-term trends predating HMOs, indirect effects of other policy changes, and other forms of competition. PMID- 3084621 TI - Medicaid myths: trends in Medicaid expenditures and the prospects for reform. AB - Medicaid expenditures, which had reached more than +32 billion by 1981, have grown substantially throughout the program's history. As a result, the conventional wisdom is that Medicaid expenditures represent a significant public policy problem. Using other measures, however, it can be shown that the program is much less of a problem than it appears to be. By 1981, spending for Medicaid represented only 12.7 percent of total state spending and had contributed only 14.2 percent to the overall growth in state expenditures since 1965. Moreover, considering only the funds which states raise from in-state sources, the median share of state budgets accounted for by Medicaid was just 5.6 percent, and only 7 states spent as much as 9 percent of their own money on the program. These figures suggest that the marginal reductions in Medicaid expenditures which would result from typical program changes are likely to be so small that rational state officials might be unwilling to incur the political opposition of powerful provider groups or the resistance of large state bureaucracies by proposing substantial reforms. The major exceptions are the few states with very large programs where even small proportional savings would amount to millions of dollars. We conclude that, given its present federal-state form and the current distribution of expenditures, it is unlikely that major reforms will be enacted because the stakes are too small for most states and the federal interest is too diffused. PMID- 3084622 TI - Comparative histochemical studies of glycosidase activity in some helminths. AB - Comparative histochemical studies of glycosidase activity were carried out in Clonorchis sinensis, Eurytrema pancreaticum, Fasciola hepatica, Dipylidium caninum, Hymenolepis nana, Ascaris suum, Toxocara canis, Ancylostoma caninum, Trichuris vulpis and Dirofilaria immitis. The enzymes examined were: N-acetyl beta-glucosaminidase (EC 3.2.1.30), beta-glucuronidase (EC 3.2.1.31) and beta galactosidase (EC 3.2.1.23). There were variations in enzyme distribution and intensity among the species and also between trematodes and nematodes; no marked positive reaction for these enzymes occurred in cestodes. In some trematodes, the caeca, especially in the brush border, and the tegument, subtegumental cells and testes, were reactive to the enzymes. In nematodes, although there was variation in reactions among species, N-acetyl-beta-glucosaminidase and beta-galactosidase were localized in the hypodermis and lateral cords excluding the excretory canal, and coelomocytes, intestinal epithelium and the walls of the reproductive systems. PMID- 3084623 TI - Techniques for locating isotopically labelled schistosomula of Schistosoma mansoni in host tissues for ultrastructural investigations. AB - The use of 75 Selenomethionine labelled cercariae of Schistosoma mansoni for ultrastructural localization of parasites in host tissues has been evaluated. Both gamma counting of tissue, and autoradiography of resin-embedded tissue were successful. The autoradiographic technique was more sensitive and schistosomula were readily located in pulmonary tissue up to 24 days post-infection. PMID- 3084624 TI - Calmodulin: localization in plant tissues. AB - Calmodulin was purified from bovine brain by preparative SDS-polyacrylamide gel electrophoresis. The denatured, purified calmodulin was used to immunize rabbits to produce antiserum. This antiserum was used to study the distribution of calmodulin in plant tissues by indirect immunohistochemistry. The root tips from corn seeds, oat seeds, peanuts, spaghetti squash seeds, and the terminal buds of spinach were investigated. A method for plant tissue sectioning and inhibition of endogenous peroxide activity was developed. In the corn root section, reaction product from anti-calmodulin was found mainly in the root cap cells. Lesser but significant amounts of calmodulin were localized in metaxylem elements, in some stele cells surrounding metaxylem elements, in apical initials, and in the cortical cells. Similar findings were also observed in other root tips from oat seeds, peanuts, and spaghetti squash seeds. In the terminal buds of the spinach, calmodulin-stained cells were highly concentrated in the apical meristem and leaf primordium. These findings suggest that the high concentration of calmodulin in the root cap may be important in relation to gravitropism and growth development. PMID- 3084625 TI - A new fluorescent detection system for identifying variant hemoglobins after gel electrophoresis using immunobinding with monoclonal antibodies. AB - This paper describes a low-resolution system for identifying variant hemoglobins with great sensitivity and specificity. After electrophoresis of the hemoglobin sample in a gel, fixation is used to entrap the hemoglobin. The gel is dried, incubated with a monoclonal antibody against the desired hemoglobin, then incubated with a second antibody against the first antibody which is conjugated with the enzyme beta-d-galactosidase. An enzyme overlay membrane containing a fluorogenic substrate is then placed on the gel surface, incubated, and removed, yielding an immunofluorescent print. The entire procedure takes only two hours, and by virtue of fluorescent detection gives sharper band resolution and greater sensitivity than conventional dye methods. The system clearly distinguishes SS sickle-cell hemoglobin from heterozygous and "S-like" hemoglobins. The technique therefore holds promise as a powerful probe for allelic variants. PMID- 3084626 TI - Two embryonic, tissue-specific molecules identified by a double-label immunofluorescence technique for monoclonal antibodies. AB - We identify two tissue-specific molecules in the sea urchin embryo by an immunofluorescence technique capable of co-localizing monoclonal antibodies on the same tissue section. The technique uses monovalent Fab-fluorochrome conjugates as secondary reagents to avoid cross-talk of subsequent antibody probes. Using this technique, we show that two cell surface molecules are expressed by different cell populations in the embryo. The technique is generally applicable for antibodies regardless of species or subtype specificity, and uses commercially available reagents. The technique provides sufficient amplification and resolution for analytical work, yet is rapid enough for screening procedures. As a fluorescent counterstain, use of the dye 4-acetamido-4' isothiocyanatostilbene-2,2'-disulfonic acid (SITS) in the protocol provides a distinct fluorescent background staining of the tissue without interference with the specific antibody staining. PMID- 3084627 TI - A histological comparison of phase-partition fixation with fixation in aqueous solutions. AB - In phase-partition fixation, tissue is immersed in a non-aqueous solvent at equilibrium with an aqueous solution of a fixing agent to minimize osmotic effects. Preservation of morphology afforded by phase-partition fixation using formalin and glutaraldehyde and several organic solvents was compared to aqueous 10% neutral buffered formalin fixation for five tissues. It was shown that phase partition fixation can provide excellent fixation for light microscopy if the proper combinations of fixatives and solvents are used. PMID- 3084629 TI - Antibody levels to Mycoplasma pneumoniae in sera collected from healthy blood donors of Wellington, New Zealand, during 1976-80. AB - The sera of healthy blood donors from the Wellington area of New Zealand, collected between 1976 and 1980, were analysed by the complement fixation test for antibody to Mycoplasma pneumoniae. A high prevalence of antibody to this organism was demonstrated and the occurrence of an M. pneumoniae epidemic in New Zealand within the survey period was shown to be reflected in the immune status of this healthy adult population. This would suggest that during an epidemic many people within the Wellington community may have M. pneumoniae infections involving little overt illness. PMID- 3084630 TI - Hemorrhagic fever with renal syndrome in Czechoslovakia: detection of antigen in small terrestrial mammals and specific serum antibodies in man. AB - A direct ELISA technique was used for demonstration of HFRS virus antigen in suspensions of the lungs obtained from 774 wild small mammals belonging to 13 zoological species trapped in 21 localities in Czechoslovakia between 1983 and 1984. Western serotype of HFRS virus was demonstrated in the lungs of 8 Microtus arvalis voles caught in the areas of central Bohemia, southern Moravia and western Slovakia, and in one Clethrionomys glareolus vole from the area of eastern Slovakia. The eastern serotype antigen was found in one Apodemus agrarius field mouse captured in the area of eastern Slovakia. The antigen titres as determined in the lungs of these rodents by the ELISA and RIA techniques were relatively high. Human sera examined for the presence of HFRS-specific antibody by the indirect fluorescence and RIA techniques were 76 serum specimens from chronic kidney patients treated by hemodialysis and 349 sera of adult males over 35 years of age coming from various districts of Bohemia and Moravia. Antibodies against HFRS virus antigen were found in 4 sera obtained from northern Bohemian men. The results provide the evidence which suggests that the natural foci of HFRS are likely to occur across much of the Czechoslovak territory, and confirms the focality of this infection in at least some of the localities characteristic in the 1950s and 1960s of the incidence of severe sporadic cases of HFRS. PMID- 3084631 TI - B cell growth factor activity of interferon-gamma. Recombinant human interferon gamma promotes proliferation of anti-mu-activated human B lymphocytes. PMID- 3084628 TI - Tuberculous meningitis--clinical and laboratory review of 100 patients. AB - In developing countries tuberculous meningitis is a difficult infection to differentiate from other central nervous system (CNS) infections. This paper presents the history, physical findings, laboratory data, and clinical course of 100 patients who were admitted to a special ward and had CSF cultures positive for Mycobacterium tuberculosis. Fifty-four patients were comatose when admitted and 76 had meningeal signs. Mean admission CSF values were WBC 531, glucose 23 mg/dl, and protein 166 mg/dl. Only two CSF AFB smears were positive. Sixty-one percent of the chest X-rays taken were consistent with pulmonary tuberculous and 39% were normal. Twenty-four patients died within the first week after admission, before the clinical diagnosis was made and anti-tuberculous therapy could be started. Fifty-three of 76 patients given antituberculous therapy died. Neurologic sequelae developed in 48% of the survivors. The high mortality and morbidity rates in this patient-group were due to the severity of illness on admission and the predominance of children (54%). PMID- 3084632 TI - Phenotypic analysis of thymocytes that express homing receptors for peripheral lymph nodes. AB - Thymocytes that express high levels of homing receptors for peripheral lymph nodes can be detected with the monoclonal antibody MEL-14. We have shown that in adult mice these rare MEL-14hi thymocytes a) are cortical in location and typically constitute 1 to 3% of the total thymocyte population, b) may be a major source of thymus emigrants, and c) contain a high frequency of precursors of alloreactive cytotoxic T lymphocytes. In this study we have analyzed the phenotype of the MEL-14hi thymocyte subset. Most normal adult MEL-14hi thymocytes are midsize and express the mature phenotype typical of thymus emigrants, medullary thymocytes, and peripheral T cells: they are predominantly PNAlo, H 2K+, Thy-1+, Ly-1hi, and either Lyt-2-/L3T4+ or Lyt-2+/L3T4-. These findings argue strongly for the presence of rare MEL-14hi immunocompetent cortical thymocytes that, aside from their homing receptor expression, are phenotypically indistinguishable from medullary thymocytes. However, a minority (20 to 30%) of MEL-14hi thymocytes are large and phenotypically nonmature: they express intermediate to high levels of PNA binding sites, and are H-2K- to H-2Klo, Thy 1hi, Ly-1+, and either Lyt-2+/L3T4+ or Lyt-2-/L3T4-. Through a technique that selectively labels outer cortical cells, phenotypically nonmature MEL-14hi thymocytes have been shown to be concentrated in the subcapsular blast region of the outer cortex. Although we have no direct evidence of a precursor-product relationship, we consider it likely that the phenotypically nonmature outer cortical MEL-14hi lymphoblasts give rise to phenotypically mature MEL-14hi cells located deeper in the cortex. These results are consistent with our previous proposal that MEL-14hi thymocytes are a major source of thymus emigrants, and indicate that expression of high levels of MEL-14-defined homing receptors may be closely linked to the intrathymic selection process. PMID- 3084633 TI - Dual immunofluorescence studies of cortisone-induced thymic involution: evidence for a major cortical component to cortisone-resistant thymocytes. AB - Cortisone-resistant thymocytes (CRT) have been used as the experimental equivalent of medullary thymocytes for the past 15 yr. Studies with CRT have provided evidence that the medullary population is similar to mature T cells in phenotype and function and may therefore be the major source of thymus emigrants. However, we have recently demonstrated that CRT differ from medullary thymocytes in their expression of the homing receptor molecule recognized by the monoclonal antibody MEL-14. Thus, many CRT express high levels of the MEL-14-defined homing receptor, whereas medullary thymocytes are MEL-14- to MEL-14lo. In normal adult mice, only 1 to 3% of thymocytes are MEL-14hi; these cells are located exclusively in the cortex and many are phenotypically and functionally mature. In this study we have used dual immunofluorescence techniques to further characterize those thymocytes resistant to cortisone treatment. Aside from being of mature phenotype with respect to expression of peanut agglutinin binding sites and the cell surface molecules H-2K, Ly-1, Lyt-2, and L3T4, CRT can be divided into MEL-14lo and MEL-14hi subpopulations, suggesting that they may actually be derived from both the medullary and the MEL-14hi cortical thymocyte subsets. PMID- 3084634 TI - Ontogeny of lymphocyte homing receptor expression in the mouse thymus. AB - The monoclonal antibody MEL-14 has been used in conjunction with immunohistology and multiparameter immunofluorescence to identify and characterize homing receptor-bearing thymocytes at various stages of embryonic and neonatal development. MEL-14hi thymocytes first appear at day 14 of gestation and come to represent about 40% of day 15 fetal thymocytes. Thereafter, the proportion of MEL 14hi thymocytes rapidly declines such that by birth (usually the 20th day of embryonic development) only about 2% of thymocytes are MEL-14hi. Although newborn thymocytes resemble adult thymocytes in this respect, the phenotypic characteristics of fetal and neonatal MEL-14hi thymocytes suggest that this unique subset undergoes a gradual transition from containing exclusively phenotypically immature cells in early gestation to containing predominantly phenotypically mature cells by young adulthood. Thus, virtually none of day 15 MEL-14hi fetal thymocytes are peanut agglutinin (PNA)lo, Ly-1hi, or either Lyt-2 /L3T4+ or Lyt-2+/L3T4-, whereas in the weeks that follow a steadily greater proportion of MEL-14hi thymocytes come to express this mature pattern (roughly 70% at 4 wk of age). Most day 15 MEL-14hi fetal thymocytes appear to express the functional homing receptor molecule, since day 15 fetal thymocytes bind to peripheral lymph node high endothelial venules about 40 to 50% as well as do adult mesenteric node lymphocytes, whereas adult thymocytes bind only about 5% as well. We have also identified a population of outer cortical MEL-14hi Lyt-2-/L3T4 lymphoblasts that appears during thymus regeneration 5 to 6 days after the administration of hydrocortisone. These lymphoblasts express the same phenotype as cells that constitute 40% of the day 15 fetal thymus and only 0.4% of normal adult thymocytes, implying that this particular subset may make up a significant fraction of thymocytes whenever there is a requirement for rapid expansion of the intrathymic and/or peripheral T cell pools. Taken together, these results are consistent with the notion that expression of the MEL-14-defined homing receptor may be closely linked to important intrathymic events that may occur early in T cell development and yet still have an overriding impact on the selection of those thymocytes that will serve as precursors of thymus emigrants. PMID- 3084635 TI - Differential ability of fixed antigen-presenting cells to stimulate nominal antigen-reactive and alloreactive T4 lymphocytes. AB - The capacity of paraformaldehyde-fixed human antigen-presenting cells (APC) to induce responses by autologous, freshly isolated peripheral blood T4 cells was examined and was compared with their ability to stimulate allogeneic T4 cell DNA synthesis. Fixation of glass-adherent cells (AC) with as little as 0.06% paraformaldehyde abolished leucine incorporation, whereas fixation with 0.75% paraformaldehyde caused death of greater than 98% of the AC. Control APC were able to take up and present the soluble antigens streptokinase-streptodornase (SK SD), tetanus toxoid, or tuberculin-purified protein derivative to autologous Ia depleted T4 cells. Fixation with greater than 0.06% paraformaldehyde eliminated such ability. When AC were incubated with antigen overnight and were then fixed, however, they were able to present nominal antigen to autologous T4 cells in a genetically restricted manner that was blocked by monoclonal antibodies directed against monomorphic determinants on class II major histocompatibility complex (MHC) molecules. Despite the ability to present nominal antigen, paraformaldehyde fixed AC were unable to induce allogeneic T4 cell proliferation. Similar results were observed when non-T cells or spleen cells were used as stimulators. The inability of fixed APC to stimulate allogeneic T4 cell DNA synthesis was not reversed by increasing the number of fixed APC or by the addition of control AC autologous to the responding cells. Moreover, interleukins 1 and 2 either alone or in combination also failed to permit maximal T cell proliferation in response to fixed allogeneic APC. The differential effects of fixation on nominal antigen and alloantigen presentation could not be explained by the loss of membrane thymocyte stimulatory activity on fixed AC. These results indicate that antigen bearing fixed APC are competent to stimulate proliferation by antigen-reactive T4 cells, but are deficient at inducing allogeneic T4 cell DNA synthesis. The differential sensitivity of these two Ia-restricted functions of APC to chemical denaturation (reductive methylation) by paraformaldehyde suggests that the allodeterminants and restriction elements for nominal antigen on MHC class II molecules can be functionally dissociated. PMID- 3084636 TI - Dual fluorochrome analysis of human B lymphocytes: phenotypic examination of resting, anti-immunoglobulin stimulated, and in vivo activated B cells. AB - B cell-enriched preparations were prepared from human peripheral blood and lymphoid tissues by the depletion of T cells and monocytes. Only B cells by virtue of their staining with anti-B1 conjugated to fluorescein were additionally examined. Dual fluorescence staining and flow cytometric analysis demonstrated that the majority of "resting" human peripheral blood and splenic B cells co express the B cell-restricted B1 and B2 antigens and lack B5, a B cell-restricted activation antigen, and interleukin 2 receptor (IL 2R). In contrast, nearly 2/3 and 1/3 of B1+ cells isolated from lymph node expressed IL 2R and B5 antigens, respectively. When B1+ B cells from peripheral blood and spleen were "activated" by anti-Ig, they lost the B2 antigen and acquired the B5 and/or IL 2R antigens. 2/3 of B1+ cells strongly expressed IL 2R, and up to 1/2 of B1+ cells co expressed B5. Delineation of increased numbers of B1+ cells that co-express B5 and/or IL 2R within lymphoid tissues obtained from patients with diseases characterized by "activated" B cells provides in vivo confirmation that these phenotypic changes correlate with B cell activation. We believe that the identification and isolation of these and similar subsets of cells defined by differing cell surface phenotypes should further our understanding both of normal B cell activation and the pathophysiology of B cell disease states. PMID- 3084637 TI - Effect of gamma radiation on resting B lymphocytes. I. Oxygen-dependent damage to the plasma membrane results in increased permeability and cell enlargement. AB - Although the susceptibility of resting B lymphocytes to radiation-induced interphase death is well known, the mechanism by which this occurs is not understood. In this report, we use three measures of plasma membrane integrity (increase in cell volume, uptake of trypan blue, and release of 51Cr) to assess the effect of radiation on the resting B cell plasma membrane. The delivery of 500 to 1000 rad caused the majority of resting B cells to enlarge slightly, whereas 3000 rad caused virtually all of the cells to approximately double in size within 3 to 4 hr. Measurement of the release of 51Cr from resting B cells revealed a similar relationship between the dose of radiation and the loss of radioactive label. Trypan blue exclusion was also found to diminish as a function of radiation dose. An analysis of a variety of lymphoid cells suggested that sensitivity to the membrane damaging effects of gamma radiation was in the order of resting B cells greater than resting T cells greater than a long-term L3T4+ T cell clone greater than a B cell lymphoma. LPS-induced B cell blasts treated with 3000 rad were equivalent to 1000 rad-treated resting B cells. The effects of the gamma radiation could be ameliorated by excluding oxygen (a diradical molecule that can potentially enhance the generation and propagation of highly reactive free radicals) at the time of irradiation, or by adding the free radical scavenging agent cysteamine. These data are compatible with the hypothesis that gamma radiation results in damage to the plasma membrane of resting lymphocytes via the generation of highly reactive free radical species. This damage is reflected in a rapid increase in plasma membrane permeability and swelling of the cells, and may play a major role in causing interphase death. PMID- 3084638 TI - Immunohistochemical analysis of the rat central nervous system during experimental allergic encephalomyelitis, with special reference to Ia-positive cells with dendritic morphology. AB - The rat central nervous system (CNS) during experimental allergic encephalomyelitis (EAE) was analyzed immunohistochemically from the preclinical to recovery stage by using monoclonal antibodies specific for rat T lymphocyte subsets and Ia antigen. Through combination of the avidin-biotin technique and carefully selected fixative, cells with dendritic morphology (DC) and infiltrating mononuclear cells were clearly and intensely demonstrated in the CNS parenchyma during EAE. In normal and complete Freund's adjuvant (CFA)-injected controls, there were no inflammatory foci. Ia (OX3)-positive parenchymal cells were not detected, whereas W3/25 stained DC that were located mainly in the white matter and W3/13 stained axons. At the preclinical stage, 11 days after CNS/CFA sensitization, a few clusters of Ia+ DC were detected in some sections of the spinal cord. The number of Ia+ DC increased as clinical signs developed (P less than 0.001). In rats with a clinical score of 1 or 2, Ia+ DC were mainly located in the perivascular region and closely associated with infiltrating T lymphocytes. However, at moribund state (score 3), Ia+ DC were evenly distributed in gray and white matter on almost all sections of the spinal cord. In recovered rats, the numbers of inflammatory foci and Ia+ DC were less than those in clinical EAE rats (P less than 0.001). Rats without clinical signs throughout the course also contained a few clusters of Ia+ DC. Double immunofluorescent staining with OX3 and anti-glial fibrillary acidic protein (GFAP) antiserum demonstrated that Ia+ DC were negative for GFAP. Their morphology and distribution were similar to those of nucleoside diphosphatase-positive cells, suggesting that Ia+ DC are microglia. In contrast to DC, no astrocytes or endothelial cells express detectable levels of Ia antigen in control and clinical EAE rats. These findings suggest that brain cells other than Ia+ DC may not be involved in the local immune interaction. Ia+ DC may play a significant role in antigen presentation in the CNS with EAE. PMID- 3084639 TI - Interleukin 1 production by human polymorphonuclear neutrophils. AB - The purpose of this study was to determine whether human polymorphonuclear neutrophils (PMN), which share a common cell lineage with macrophages, could produce factors such as IL 1. Other properties which these two cell types share are their phagocytic nature and the common receptor and antigens on their cell surfaces. IL 1, in many of its physical, biochemical, and functional characteristics, is found to resemble endogenous pyrogen (EP). PMN have been cited as a possible cell source of EP, but there have also been reports in which the capacity of PMN to produce EP has been questioned. This study shows that normal human PMN can be stimulated by particulate agents such as zymosan and soluble agents such as phorbol myristic acetate to produce a factor(s) which induces proliferation of mouse thymocytes, i.e., PMN IL 1. This PMN IL 1 was released from PMN in a dose- and time-dependent fashion. PMN IL 1 was nondialyzable, was heat-labile, and was inactivated at pH below 5 and above 8. PMN IL 1 stimulated the proliferation of normal human synovial fibroblasts and caused release of a neutral protease (plasminogen activator) from synovial cells. The synovial and thymocyte-proliferating capacity of PMN IL 1 was not affected by the protease inhibitor aprotinin or by soybean trypsin inhibitor. Gel filtration studies estimate the m.w. of PMN IL 1 to be approximately 13,000 to 17,000. PMID- 3084640 TI - Partial amino acid sequence and genetic control of latent a2 allotype induced in rabbits by immunization with anti-a2 antibody. AB - We have shown that after immunization of homozygous a1 rabbits of the B immunoglobulin (Ig) heavy chain haplotype with anti-a2 antibody (Ab) a population of molecules appears that has all of the serologic characteristics of the a2 allotype. We have now isolated these putative latent a2 molecules, have separated the heavy chains, and after enzymatic deblocking, have determined the first 19 N terminal amino acids. For all eight allotype-associated residues, these putative latent a2 molecules have the amino acid residues typical of a2 allotype. As expected, the preimmune IgG from this a1a1 rabbit has the amino acids typical of the a1 allotype. Thus by partial amino acid sequence analysis, we provide additional evidence that the latent a2 allotype can be induced in a1a1 rabbits of the B heavy chain haplotype by immunization with anti-a2 Ab. Rabbits of other heavy chain haplotypes were also immunized with anti-a2 Ab and were tested for their ability to synthesize latent a2 allotype. Thus far, a1a1 rabbits of the A, B, C, and I heavy chain haplotypes all synthesize latent a2 allotype. In contrast, a3a3 rabbits of the G and H heavy chain haplotypes did not synthesize latent a2 allotype. PMID- 3084641 TI - A novel idiotopic determinant on phosphorylcholine-binding immunoglobulins restricted to isotype and allotype. AB - A shared idiotopic (Id) determinant, designated B24-50, was detected on phosphorylcholine (PC)-binding myeloma proteins by using a monoclonal antibody. Analysis of immune sera from inbred and congenic strains of mice revealed the presence of this Id determinant on a very small proportion of the PC-binding immunoglobulins (Ig). Hybridoma and myeloma proteins of various classes were analyzed for B24-50 expression, and a clear association of B24-50 with IgA was demonstrated. The Id was found on two distinct idiotypic families, (TEPC15 and McPC603), which share a similar heavy chain but have different light chains; however, isolated heavy chains did not express B24-50. The Id did not require the absolute association of the TEPC15 light chain V kappa 22 with the TEPC15 heavy chain but appeared dependent upon the interaction of the light chain with the TEPC15 heavy chain via quaternary interactions and/or shared amino acid residues of V kappa 8 (M603) and V kappa 22. Furthermore, B24-50 was not found on IgA of strains with the Ighb allotype. Thus B24-50 is a novel isotype-restricted determinant found on two Id families and is influenced by the Igh allotype. PMID- 3084642 TI - Xid and normal mice express a light chain-associated cross-reactive idiotype in response to (T,G)-A--L and (T,G)-A--L-mBSA. AB - Rabbit anti-idiotypic (Id) antibodies were prepared against purified ascites anti (T,G)-A--L antibodies (TGB5) that had been absorbed to remove A--L-specific antibodies and were specific for (T,G)-side chain determinants. Purified rabbit anti-TGB5 Id antibodies detected an allotype-independent, light chain-associated cross-reactive Id expressed by the majority of individual mice immunized with (T,G)-A--L, (T,G)-A--L coupled to methylated bovine serum albumin (mBSA), or the linear terpolymer GAT. Primary and secondary monoclonal hybridoma protein (HP) antibodies from X/Xxid heterozygous (wild-type) mice immunized with (T,G)-A--L and/or (T,G)-A--L-mBSA were analyzed for isotypy and were grouped into eight antibody fine specificity sets defined by the patterns of direct binding to the antigens (T,G)-A--L, (Phe,G)-A--L, (T,G)-Pro--L, GT, and A--L. Analysis of these primary and secondary HP for TGB5 idiotypy showed a preferential expression of the TGB5 Id among GT+-binding HP (antibody fine specificity sets 1 through 3). All of the primary GT+-binding HP and the majority of secondary GT+-binding HP (sets 1 through 3) were TGB5 Id+. Most but not all of the TGB5 Id+ HP bound GAT. Of the side-chain-specific HP (sets 1 through 7), 78% of primary HP vs 49% of secondary HP bound GT. By these criteria, the primary HP response appears more restricted than the secondary HP response, consistent with the idea that Id diversification and antibody heterogeneity are regulated and selected events occurring during memory B cell generation. Although xid mice produce less antibody than wild-type mice to (T,G)-A--L, the TGB5 Id was produced early in the primary response by both xid and wild-type mice immunized with (T,G)-A--L or (T,G)-A--L-mBSA, and was maintained as a detectable Id in equivalent amounts in their secondary serum antibody responses. These results support the idea that distinct B cell subsets, including the xid B cell subset, share the same immunoglobulin gene repertoire. PMID- 3084643 TI - Xenogeneic antibodies with apparent public idiotypic specificity for anti-Ia.7 antibodies are directed in part against V kappa 21D and E subgroup marker. AB - Public idiotypes (IdX) expressed on monoclonal antibodies (mAb) against a monomorphic alpha-chain determinant of the I-E molecule (Ia.7 epitope cluster I) have been studied by using xenogeneic anti-Id reagents derived from pig, rabbit, and rat. IdX+ anti-Ia.7 mAb were recently demonstrated to be structurally related by a high frequency expression of the V kappa 21E light chain subgroup. This raised the question of whether V region determinants of the IdX were related to V kappa 21E sequences or whether they were unique to hypervariable regions of Ia.7 binding antibodies. To clarify this question, the possible association between the expression of the public Id (IdX(s)Ia.7) and the presence of V kappa sequences (V kappa 21E and/or J kappa segment) was examined. The reactivity of the anti-Id reagents with a random panel of 28 myeloma products (each containing a light chain from one of the different V kappa 21 subgroups) was studied by assaying the ability of these mAb to inhibit the binding between the anti-Id and anti-Ia.7 mAb. This analysis demonstrates that what has previously been defined as IdX Ia.7 includes determinants shared by V kappa 21E and V kappa 21D light chain V regions. The structures recognized are expressed irrespective of the J kappa segment. In addition, this study demonstrates interspecies variation in immune responses to such V kappa 21E antigenic determinants. Additional IdX components are found on anti-Ia.7 mAb but not on other V kappa 21E or D proteins. Thus V region subgroup considerations have crucial implications for Id characterization. In addition, this work describes the first division of the V kappa 21 subgroup into component parts by a mAb. PMID- 3084644 TI - Human T lymphocytes and monocytes bear the same Leu-3(T4) antigen. AB - An analysis of the cellular distribution, biosynthesis, and structure of the human T lymphocyte antigen Leu-3(T4) was performed. By using a sensitive ELISA as well as FACS analysis, relative quantities of the Leu-3(T4) antigen from whole cell lysates and from cell surfaces of six cell lines were determined. The T-T hybrid cell line 255.88, and the monocyte/macrophage cell line U937, proved to be high producers of the antigen and were chosen for additional investigation. The Leu-3(T4) antigens from the T lymphocyte cell line and the monocyte/macrophage cell were shown to be identical by SDS-PAGE. Leu-3(T4) was a polypeptide of 55,000 AMW under reducing conditions, and 63,000 AMW under nonreducing conditions. In the 255.88 cell line, a second band of 41,000 AMW was associated with the true Leu-3(T4) molecule. The 55,000 AMW Leu-3(T4) molecule was shown to possess a high mannose sugar side chain, and to contain few accessible tyrosine residues. These studies demonstrate that human T lymphocytes and monocytes produce and process similar molecules that react with the anti-Leu-3(T4) monoclonal antibody. They also characterize this important associative antigen recognition structure and suggest that cells other than the T lymphocyte may be targets for the retrovirus HTLV-III. PMID- 3084645 TI - Induction of protective immunity against Schistosoma mansoni by a nonliving vaccine. II. Response of mouse strains with selective immune defects. AB - The efficacy of a new vaccination procedure against Schistosoma mansoni, involving intradermal injection of nonliving antigen combined with the bacterial adjuvant Mycobacterium bovis strain bacillus Calmette Guerin, was tested in several strains of mice. Development of protection against subsequent infection was compared with in vivo skin test reactivity and in vitro humoral reactivity to soluble and surface-associated schistosome antigens. Significant levels of resistance and immune response were displayed by many inbred mouse strains, including C57BL/6J, C3H/HeN, and CBA/J, as well as outbred Swiss-Webster mice. However, no definite correlation was observed between the level of any particular immune response and the level of resistance to challenge S. mansoni infection. Development of protective immunity was also examined in mice with various immune defects, to determine whether these responses are relevant to resistance in this model. Animals with defective specific immediate hypersensitivity response due to deficiencies in IgE (SJL/J) or mast cell (W/Wv) production displayed strong resistance as a result of immunization. Likewise, mice bearing the lpsd (C3H/HeJ) or xid (CBA/N) mutations, affecting cellular or humoral response to certain thymus-independent antigens, developed significant levels of resistance after immunization. A/J mice, with defects in cellular recognition of bacterial endotoxin as well as deficiencies in natural killer cell activity and complement function, also showed significant protective immunity. Thus, these reactivities do not appear to be essential to the resistance against S. mansoni induced by the nonliving vaccine. Two nonresponder strains were identified, P and BALB/c. P mice were defective in specific delayed hypersensitivity response as well as resistance to infection. However, BALB/c mice showed no obvious immune deficiencies at the time of challenge. These results agreed with previous findings in mice immunized by exposure to radiation-attenuated cercariae with one exception; BALB/c mice were protected by vaccination with irradiated cercariae but not by the nonliving vaccine. Thus, further examination of immune response in mice identified in this study as high and low responder strains should allow characterization of critical immune resistance mechanisms induced by the nonliving vaccine, as well as immune mechanisms operating in common between these two models of resistance to S. mansoni. PMID- 3084646 TI - Induction of protective immunity against Schistosoma mansoni by a nonliving vaccine. III. Correlation of resistance with induction of activated larvacidal macrophages. AB - Mice protected against Schistosoma mansoni infection by intradermal (i.d.) immunization with nonliving larval or adult worm antigens plus bacterial adjuvant developed 24-hr skin test responsiveness to schistosome antigens with the histologic features of delayed hypersensitivity. Intraperitoneal antigen injection elicited a mononuclear cell-enriched exudative population containing macrophages activated for direct cytotoxicity against schistosomula and tumor cell targets. This was likely to be due to in vivo exposure to macrophage activating lymphokines, since these cells were unresponsive to further lymphokine stimulation in vitro and splenocytes from immunized mice reacted to specific in vitro antigen challenge by production of lymphokines capable of conferring larvacidal activity upon control macrophages. In contrast, mice treated with schistosome antigens by i.v. injection, which were not protected against challenge infection, failed to develop delayed hypersensitivity or activated macrophages in response to specific antigen challenge in vivo, and the titers of macrophage-activating lymphokine produced by in vitro antigen-stimulated splenocytes from these mice were threefold to fourfold lower than those produced by cells from animals immunized by the i.d. route. Thus, sensitization for cell mediated immune responses including lymphokine production and macrophage activation correlated with induction of resistance to S. mansoni in this model of vaccination. PMID- 3084647 TI - Induction of protective immunity against Schistosoma mansoni by a nonliving vaccine. IV. Fractionation and antigenic properties of a soluble adult worm immunoprophylactic activity. AB - An aqueous buffer-soluble, nonparticulate fraction of adult Schistosoma mansoni worms (SWAP) was separated by gel filtration on Ultragel AcA-34, and portions of the eluate were tested for their capacity to induce protective immunity against cercarial challenge when administered intradermally to mice in combination with the adjuvant BCG. All of the immunogenic activity was found in a single peak of protein excluded in the void volume of the column. This same fraction was determined by SDS-PAGE and Western immunoblotting to be unique in that it contained a component of Mr (X 10(-3) 97 (97,000) recognized monospecifically by antibodies from mice vaccinated with unseparated SWAP plus BCG. Similarly, the protective fraction was unique in possessing the capacity to elicit 24 hr delayed footpad swelling responses, as well as lymphokine production, in SWAP-BCG immunized mice. These results suggest that the immunogenic activity of SWAP resides in a restricted population of molecules, and possibly in the 97,000 antigen detected with antibodies from vaccinated animals. Because both the protective capacity of unfractionated SWAP and the serologic reactivity of the 97,000 antigen are sensitive to digestion with protease, it is likely that the immunologic activity of these molecules is dependent on peptide-bonded structural elements. PMID- 3084648 TI - Lysis of human solid tumor cells by lymphokine-activated natural killer cells. AB - The ability of NK cells to lyse noncultured solid tumor cells was investigated, and the results were compared with lysis of K562. Purified NK cell fractions separated by either Percoll centrifugation or a cell sorter exhibited higher level of lysis against noncultured melanoma cells than did NK-depleted cell fractions. However, the level of lysis was low (less than 10% lysis). Adding recombinant interleukin 2 (rIL 2) to the 4-hr assay induced significant lysis (more than 10%) of noncultured melanoma cells in 18 of 23 (78%) Percoll-enriched NK cell fractions and seven of 11 (64%) sorted Leu-11a+ cells at an E:T ratio of 80 and 10, respectively. In contrast, only two of 13 (14%) PBMC, five of 17 (29%) Percoll-decreased NK cell fractions, and one of 12 (8%) sorted Leu-11a- cells lysed noncultured melanomas in the presence of rIL 2. rIL 2 induced NK cells to lyse noncultured lung and breast cancer cells, as well as melanoma tumors. Exposure of NK cells to 2000 rad radiation abrogated the rIL 2-induced cytotoxicity against noncultured melanomas. Preculture of PBMC for 18 hr with recombinant interferon-gamma (rIFN-gamma) resulted in a modest level of lysis of non-cultured melanomas by sorted Leu-11a+ cells. Adding rIL 2 to the assay increased the cytotoxic activity in both rIFN-gamma-activated Leu-11a+ and Leu-7+ NK subsets. The level of noncultured tumor lysis correlated well with that of K562 lysis in all of the experiments. Purified NK cell fractions in rIL 2 cultures increased cytotoxic activity against noncultured tumor cells with incubation time for up to 3 days, and the level of NK cell-mediated lysis was dependent on both doses of rIL 2 and length of incubation. In contrast, both NK depleted and sorted Leu-11a- cells demonstrated very low levels of solid tumor lysis after 3-day cultures with a high dose of rIL 2. Killer cell precursors induced by 3-day cultures of sorted cell fractions with rIL 2 and rIFN-gamma were found in both Leu-11a+ and Leu-7+ NK subsets, but not Leu-4+ or Leu-3a+ T lymphocytes. These results indicate that NK cells become cytotoxic for noncultured solid tumor cells by a brief contact with rIL 2, and increase cytotoxic activity after culture with rIL 2. PMID- 3084649 TI - Induction and blocking of cytolysis in CD2+, CD3- NK and CD2+, CD3+ cytotoxic T lymphocytes via CD2 50 KD sheep erythrocyte receptor. AB - The 50 KD sheep red blood cell antigen receptor CD2 is the earliest T cell differentiation marker and is present on all blood-derived T cells, including natural killer (NK) cells. The CD2 antigen is also known to serve as an important activation site regulating various T cell functions. We report that anti-CD2 monoclonal antibodies (MAb) block MHC-restricted class I- and class II-specific cytolysis by CD2+, CD3+ clones of the relevant target cells, irrespective of whether lysis by these clones is blocked by anti-CD3 or anti-CD8 MAb. Moreover, anti-CD2 MAb (but not anti-CD3 MAb) are able to reduce MHC-nonrestricted, nonspecific cytolysis: a) by CD2+, CD3+ clones of K562 target cells; and b) by CD2+, CD3 NK clones of K562 as well as Daudi cells. Different preparations of anti-CD2 MAb vary in their capacity to inhibit cytolysis. For cloned effector cells, the percent inhibition of lysis by CLB-T11 greater than Lyt-3 MAb, whereas with "fresh" NK cells, the lysis inhibitory ability of Lyt-3 greater than CLB T11. The antibody-dependent cellular cytotoxicity by "fresh" and cloned NK cells is not inhibited by anti-CD2 MAb. Anti-CD2 MAb also prevent the induction of lysis by cross-linked anti-CD3 MAb, e.g., by CD2+, CD3+ cloned cloned cells against (IgG-FcR+) Daudi cells. Anti-CD2 MAb can also induce cytolysis in some, but not all, CD2+, CD3- NK clones against xenogeneic P815 mouse mastocytoma cells. Anti-CD2 MAb, in combination with lectins (PHA or Con A: pretreatment of effector cells), can also induce cytolytic activity by CD2+, CD3+ clones against Daudi cells. Our data therefore support the concept that the CD2 antigen is an important activation site regulating a wide variety of T cell functions including cytolysis. Whether ligand interaction with the CD2 antigens results in augmentation or inhibition of T cell functions may very well depend on the type of CD2 antigen-ligand interaction, e.g., cross-linked ligand-receptor interaction may, in general, enhance the various T cell functions, whereas noncross-linked ligand-receptor interactions may inhibit such functions, as we and other investigators demonstrated earlier for the CD3/Ti antigen-receptor complex activation site. PMID- 3084650 TI - Valency of CD3 binding and internalization of the CD3 cell-surface complex control T cell responses to second signals: distinction between effects on protein kinase C, cytoplasmic free calcium, and proliferation. AB - We have studied the relationship of valency of CD3 stimulation and modulation of the CD3 receptor complex with biochemical and proliferative responses of T cells. Anti-CD3 Fab, as well as F(ab')2 and whole antibody caused rapid modulation of the CD3 antigen, whereas anti-CD3 conjugated to Sepharose did not. In the absence of monocytes, T cells stimulated with anti-CD3 Fab, F(ab')2, or F(ab')2-Sepharose showed differences in their ability to respond to second signals given by PMA, IL 1, IL 2, or antibodies to Tp67 and Tp44. None of the anti-CD3 signals alone caused resting T cells to produce IL 2, and only the Sepharose-bound anti-CD3 F(ab')2 caused T cells to express high levels of functional IL 2 receptors. Anti CD3 F(ab')2-Sepharose-stimulated T cells produced IL 2 and proliferated in response to each of the second signals. Because anti-CD3-Sepharose did not cause modulation of the CD3 antigen, the ability of the Sepharose-bound antibody to induce T cells to express IL 2 receptors and to respond to individual second signals may be related to lack of modulation rather than valency of binding. Anti CD3 Fab-stimulated T cells responded to PMA but required combinations of other second signals. T cells stimulated with unmodified anti-CD3 antibody or F(ab')2 fragments responded to PMA but did not respond to any other second signals alone or in combination. Stimulations that resulted in modulation (i.e., anti-CD3 whole antibody, anti-CD3 F(ab')2, or anti-CD3 Fab fragments) caused an increase in cytoplasmic calcium levels in resting T cells but blocked proliferation of T cells in response to mitogenic lectins or CD2 stimulation. Anti-CD3 F(ab')2 on Sepharose, however, did not block T cell proliferation. Whole bivalent anti-CD3 antibody or F(ab')2 fragments, but not monovalent Fab fragments, caused a rapid translation of protein kinase C activity from cytosol to membrane in the Jurkat T cell line. Because all of these modulate the receptor, these data indicate that the functional difference between monovalent and bivalent binding to CD3 is related to antibody valency and not to antigenic modulation. The use of Fab anti CD3 stimulation that requires combinations of second signals for proliferation allowed an analysis of the functional relationships between IL 1, anti-Tp67, and anti-Tp44. PMID- 3084652 TI - The alloantibody response in the allogeneically pregnant rat. IV. Analysis of the alloantibody specificities with monoclonal antibodies. AB - We have compared the serum alloantibody population from female rats immunized either by allogeneic pregnancies or by conventional immunizations. The only allogeneic difference in both types of immunization was class I of the MHC. Pregnancy-induced alloantibodies as compared with conventionally raised alloantibodies were more homogeneous with respect to isoelectric point, and were more homogeneous as defined by competition experiments with anti-class I monoclonal antibodies. The genetic control of the pregnancy-induced alloantibody response was also verified. PMID- 3084651 TI - Expression and function of an early activation marker restricted to human B cells. AB - A B cell-specific monoclonal antibody (anti-Ba) was prepared. In two-color FACS analysis the anti-Ba reacted with a subpopulation of Ig+ or B1+ cells obtained from tonsils, but did not react with most B1+ cells derived from PBL. Activation of B cells from PBL with TPA or anti-mu induced Ba expression and the addition of PHA-conditioned supernatant with anti-mu-enhanced Ba expression. Other B cell activators, such as Staphylococcus aureus Cowan I (Staph-A) or PWM plus T cells, could induce Ba expression. Ba expression was observed 6 hr after stimulation and reached a peak level at 72 hr. Ba expression was strictly restricted to B cells. H-7, a specific inhibitor of protein kinase C (C-kinase), displayed a dose dependent inhibitory effect on Ba expression, showing dependency on C-kinase for Ba expression. Anti-Ba inhibited B cell proliferation induced by anti-mu and B BCGF distinct from BSF-1. The results presented in this study suggest that the Ba antigen on B cells may be comparable to the Tac antigen on T cells. PMID- 3084653 TI - The murine interleukin 2 receptor. IV. Biochemical characterization. AB - The IL 2 receptor isolated from the IL 2-dependent CTL-L cell line was subjected to biochemical analysis. Pulse-chase and tunicamycin studies, as well as digestion with the endoglycosidases, Endo-F and Endo-H, of 35S-methionine-labeled IL 2 receptors suggested a single protein precursor of 32,000 (p32) daltons. The p32 precursor was rapidly processed by addition of high-mannose-containing core N linked sugars to intracytoplasmic precursor intermediates of 38,000 (p38) and 40,000 (p40) daltons, which undergo further processing to yield a mature surface receptor with heterogeneous apparent m.w. of 52,000 to 65,000 (p58). Two dimensional gel studies indicated that p58 exhibited broad charge heterogeneity between pH 4.6 and 6.3. Endo-F digestions of p58 shifted the isoelectric focus point to a more basic 5.5 to 7.4. This considerable charge heterogeneity is consistent with the possibility that other posttranslational modifications to the mouse IL 2 receptor occur besides addition of complex N-linked glycans. Immunoprecipitations of the IL 2 receptor from surface iodinated cells also revealed an additional band at 110,000 (p110) daltons. IEF vs SDS-PAGE two dimensional gel studies demonstrated that p110 also had an isoelectric focus point identical to p58. Western blot studies with an anti-IL 2 receptor monoclonal antibody (7D4) demonstrated that p38, p40, p58, and p110 each expressed the epitope recognized by this antibody. Thus, it is likely that p110 is not a unique molecule that coprecipitates with the IL 2 receptor. Western blot analysis of mitogen-stimulated T and B lymphocytes also revealed bands similar to p58 and p110, although these bands had an average apparent m.w. 3000 to 6000 less than those seen for CTL-L cells. PMID- 3084654 TI - A secreted form of the human interleukin 2 receptor encoded by an "anchor minus" cDNA. AB - The DNA sequence encoding all of the putative intracytoplasmic domain and most of the trans-membrane domain of the human IL 2 receptor was deleted from a full length receptor cDNA. After expression in mouse L cells, the resultant "anchor minus" cDNA was found to direct the synthesis of a secreted rather than membrane associated form of the IL 2 receptor. The secreted receptor protein (44,000 to 46,000 Mr) retained the capacity to bind both IL 2 and the monoclonal anti-Tac antibody, as evidenced by retention on IL 2 and anti-Tac affinity columns, inhibition of [3H]-anti-Tac binding to HUT 102B2 cells, and partial inhibition of IL 2-induced CTLL proliferation. Removal of these domains from the IL 2 receptor did not alter the posttranslational processing or rate of export of the truncated receptor protein. These data confirm the proposed membrane orientation of the IL 2 receptor (NH2 terminus out, COOH terminus in) and underscore the anchoring function of this carboxy terminal receptor segment. The availability of such anchor minus receptor cDNA constructs may facilitate purification of large quantities of receptor protein for further analysis of receptor structure, valency, and localization of the IL 2 binding site(s). PMID- 3084656 TI - Characterization of small and large human peripheral blood monocytes: effects of in vitro maturation on hydrogen peroxide release and on the response to macrophage activators. AB - Human peripheral blood monocytes (HPBM) isolated from normal donors by centrifugal elutriation were divided into two populations according to volume. (Median volumes of small monocytes (SM) and large monocytes (LM) were 255 micron and 280 micron, respectively.) H2O2 production was determined during in vitro culture and in response to bacterial lipopolysaccharide (LPS), and to recombinant human interferon-gamma (rIFN-gamma). On day 1, H2O2 production by LM was significantly greater than that by SM. In vitro culture of SM resulted in an augmented ability to produce H2O2. By day 3, SM were the major H2O2 producers. Freshly isolated SM and LM, exposed for 24 hr to LPS and rIFN-gamma, showed different patterns of activation. Both SM and LM responded to LPS, with LM responding maximally at lower doses than SM. Only SM showed a significant augmentation of H2O2 production with rIFN-gamma treatment. We also assessed the effect of in vitro culture with activation. SM but not LM showed an increased H2O2 to LPS and rIFN-gamma after 7 days in culture. Continuous exposure of SM to rIFN-gamma resulted in maximal H2O2 production at day 3 of culture; this pattern was not seen for LPS. The production of H2O2 by HPBM is related to in vitro maturation. The enhanced H2O2 production by HPBM upon exposure to rIFN-gamma may be related to the induction of in vitro maturation. PMID- 3084655 TI - T cell receptor triggering induces responsiveness to interleukin 1 and interleukin 2 but does not lead to T cell proliferation. AB - The antigen-like activity of monoclonal antibodies directed at the T3-Ti antigen receptor complex of human T lymphocytes was employed to study activation requirements of resting T cells. Efficient antigen recognition (signal 1) by T lymphocytes requires multimeric antigen receptor triggering because under appropriate experimental conditions soluble ligands do not produce this initial signal for T cell activation. The latter leads to receptiveness for both interleukin 1 (IL 1) and interleukin 2 (IL 2). Importantly, induction of proliferation requires an additional signal (signal 2), namely IL 1, which appears to be required to enable optimal secretion of IL 2. In contrast, presensitized T lymphocytes do not require IL 1 for IL 2 production. In this case, antigen receptor oligomerization is in itself sufficient to induce IL 2 receptor expression, and IL 2 secretion as well. PMID- 3084657 TI - Rodent IgE-binding factor genes are members of an endogenous, retrovirus-like gene family. AB - Synthesis of IgE by B lymphocytes can be regulated by soluble lymphocyte factors which have affinity for the Fc region of IgE (IgE-binding factors). In previous studies, we identified cDNA clones encoding rodent IgE-binding factors by direct expression in transfected mammalian cells. Here we show that IgE-binding factor cDNA clone 8.3 is a member of the endogenous, retrovirus-like intracisternal A particle gene family of the mouse. This conclusion is supported by blot hybridization, DNA sequence comparisons, heteroduplex analysis, and immunochemical cross-reactivity of the encoded proteins. The results identify a member of this highly reiterated gene family with a role in regulation of the allergic immune response. PMID- 3084658 TI - Mouse x human heterohybridomas as fusion partners with human B cell tumors. AB - Surface idiotype (Id) of B cell malignancies is an excellent tumor-specific marker. We have, however, recently described heterogeneity of tumor Id in some cases. We therefore sought a way to isolate, reliably and efficiently, different species of idiotype from a potentially heterogeneous population. In this report we demonstrate our success using a series of mouse X human heterohybridomas as fusion partners with human B cell tumors. Three lines (K6H6/B5, K6H9/G12, SBC/H20) demonstrated excellent fusion efficiency with 75%-85% of wells plated containing hybrids. Two cell lines, K6H9/G12 and SBC/H20 had a tendency to secrete a single Ig chain (heavy or light chain), whereas the K6H6/B5 cell line secreted whole immunoglobulin (Ig) in greater than 80% of the hybrids. This line secreted significant amounts of Ig (2.73 micrograms/ml/10(6) cells) and was relatively stable in culture. Since this line has such a high fusion efficiency the products of normal B cells admixed with tumor may be recovered, allowing the opportunity of isolating host anti-tumor antibodies. In order to prove that hybrids were derived from the tumor, Southern blot analysis of rearranged DNA was performed in selected cases. Fusions with this line provide the potential for recovering many different species of idiotype in a mixed population. This will facilitate the production of mouse monoclonal anti-idiotype antibodies against many variants and against different idiotopes. PMID- 3084659 TI - Diverticulum of the appendix. PMID- 3084660 TI - Meningococcal disease in The Netherlands, 1959-1981: the occurrence of serogroups and serotypes 2a and 2b of Neisseria meningitidis. AB - By means of a filter radioimmunoassay and the use of monoclonal anti-2a and anti 2b antibodies, we have serotyped 3164 of 3688 strains of Neisseria meningitidis isolated from patients in The Netherlands between 1959 and 1981. Serotypes 2a and 2b were distributed differently among the major serogroups A, B, C, and W-135. Neither of the types was found among group A strains. Type 2b strains of serogroup B emerged in 1965, causing a country-wide epidemic which reached a peak incidence in March and April of 1966 and continued to predominate within group B until 1979. Type 2a strains of serogroup C were responsible for a substantial number of sporadic cases over a long period without any association with outbreaks or with a shift in the pattern of the serogroup. After the appearance of group W-135 in 1971, W-135 strains caused a small non-focal epidemic wave. The upsurge of disease due to virulent sub-populations of strains B:2b and C:2a appeared to be closely related to a basic pattern of regular cyclical waves with peak intervals which differed for serogroups A, B, and C. In recent years both serotype 2a and 2b strains within the different serogroups fell to insignificant numbers. Our results show that retrospective large-scale serotyping of collected strains provides insight into the epidemiological patterns of endemic meningococcal disease. PMID- 3084661 TI - Lactobacillus endocarditis. AB - Two cases of endocarditis due to Lactobacillus plantarum and Lactobacillus casei var. rhamnosus are described. Both patients were successfully treated medically. The response of the two isolates to a range of concentrations of penicillin in an apparatus which continuously monitored growth is reported. The strain of L. casei var. rhamnosus was found to be penicillin tolerant. The use of a combination of a penicillin with gentamicin to treat endocarditis due to penicillin tolerant strains of lactobacillus is discussed. The criteria for selecting oral agents to follow intravenous therapy are assessed also. PMID- 3084662 TI - Comparison of hemolymph proteins from resistant and susceptible oysters, Crassostrea virginica, exposed to the parasite Haplosporidium nelsoni (MSX). PMID- 3084663 TI - Tau (tau) virus infection of Carcinus mediterraneus: histology, cytopathology, and experimental transmission of the disease. PMID- 3084664 TI - Ophthalmia neonatorum in Nairobi, Kenya: the roles of Neisseria gonorrhoeae and Chlamydia trachomatis. AB - Among 149 consecutive infants with ophthalmia neonatorum in Nairobi, Neisseria gonorrhoeae was recovered from 43%, Chlamydia trachomatis from 13%, and both microorganisms from 4%. Three of five isolates of C. trachomatis belonged to trachoma serovars. The sensitivity and specificity of a gram-stained smear for the diagnosis of gonococcal conjunctivitis were 86% and 90%, respectively. Patients with gonococcal conjunctivitis had more purulent discharge, a higher clinical severity score, and a younger age at onset of disease. Corneal epithelial edema with superficial keratitis was present in four (16%) of 25 patients with gonococcal conjunctivitis but in none of 22 other patients (P = .07). N. gonorrhoeae or C. trachomatis was isolated from the pharynx in 11 (15%) and six (23%) cases, respectively. Oropharyngeal gonococcal infection was associated with coughing (P = .007). PMID- 3084665 TI - Potential value of rectal-screening cultures for Chlamydia trachomatis in homosexual men. AB - We compared the potential value of rectal-screening cultures for Chlamydia trachomatis and Neisseria gonorrhoeae among homosexual men attending a sexually transmitted disease clinic and also assessed the relation of either infection to patient age, symptoms, history of previous infection, and likelihood of early treatment. Of 1,429 homosexual men cultured over a six-month period, 118 (8%) had gonococcal rectal infection, 72 (5%) had chlamydial rectal infection, and 15 (1%) had both. The prevalence of rectal chlamydial infection was strongly related to age, with the highest occurrence in adolescents. C. trachomatis was isolated more often from men infected with N. gonorrhoeae (11%) than from men not infected with N. gonorrhoeae (5%; P = .01), and simultaneous urethral infection in patients with positive rectal cultures occurred more frequently in men infected with N. gonorrhoeae than in men infected with C. trachomatis (27% vs. 14%, respectively; P = .05). The majority of rectal infections with N. gonorrhoeae and C. trachomatis in this population were asymptomatic. Although 80% of the patients who had rectal infection with N. gonorrhoeae were appropriately treated on the initial clinic visit, only 18% of those with rectal chlamydial infections received proper treatment (P less than .0001). The yield of patients who were newly identified and brought to treatment was 4.8 patients per 100 screening cultures for C. trachomatis vs. 1.9 patients per 100 screening cultures for N. gonorrhoeae. PMID- 3084666 TI - A spontaneous mutant of Neisseria gonorrhoeae with decreased resistance to neutrophil granule proteins. AB - We examined the resistance of Neisseria gonorrhoeae to proteins prepared from the granules of human polymorphonuclear neutrophils (PMNs). We found that nearly isogenic strains differing in lipopolysaccharide subunit molecular weight also differed in levels of resistance to crude granule extracts. N. gonorrhoeae strain WS1 was at least 10-fold less resistant than the parental strain FA 102 to granule extracts. Surprisingly, strain WS1 did not differ from FA 102 in resistance to two isolated antimicrobial proteins obtained previously from extracts of human PMN granules. We used strain WS1 in assays that detected antimicrobial proteins in granule extracts, and we obtained at least two proteins with apparent molecular masses of 24-25.5 kilodaltons that exerted potent in vitro antigonococcal activity. We found that the ED50 (concentration of protein required to kill 50% of gonococci) against the strain WS1 was approximately 0.006 microgram of protein/ml, whereas the ED50 against the parental strain (FA 102) was approximately 0.4 microgram of protein/ml. Accordingly, alterations in lipopolysaccharide structure apparently caused a 66-fold decrease in gonococcal resistance to granule proteins. Our data suggest that gonococcal resistance to oxygen-independent antimicrobial systems of human PMNs may, in part, depend on the availability of certain lipopolysaccharide domains involved in recognition of the antimicrobial granule proteins described in this report. PMID- 3084667 TI - Augmented induction of interferons during Listeria monocytogenes infection. AB - Mice infected iv with an immunizing dose of the gram-positive bacterium, Listeria monocytogenes, produced circulating interferon (IFN) during the inductive phase of the immune response to Listeria. Listeria infection also dramatically altered the host's responsiveness to IFN-inducing agents. Within 24 hr of infection, mice acquired a 50-fold greater than normal capacity to produce the IFN alpha and/or IFN beta classes (IFN alpha/beta) following iv injection of endotoxin. Serum levels of IFN alpha/beta peaked by 2 hr, after which high levels of IFN gamma were detected in the sera of Listeria-infected mice given the B cell mitogen. Similar studies carried out with the interferon-inducing agent polyinosinic polycytidylic acid (poly(I).poly(C) revealed that mice infected for 24 hr produced only 4-8 times more IFN alpha/beta than did noninfected mice. Unlike endotoxin, however, poly(I).poly(C) did not induce IFN gamma in Listeria-infected animals. PMID- 3084668 TI - Significance of local gamma interferon in recurrent herpes simplex infection. PMID- 3084669 TI - High-level resistance to gentamicin in Streptococcus faecalis: risk factors and evidence for exogenous acquisition of infection. AB - Between November 1981 and October 1984, 48 of 3,456 clinical isolates of Streptococcus faecalis that were studied showed high-level (greater than 2,000 micrograms/ml) resistance to gentamicin. A case-control study comparing patients with gentamicin-susceptible (MIC less than 64 micrograms/ml) and -resistant S. faecalis infections showed significant associations (P less than .01) between the development of infection with highly gentamicin-resistant S. faecalis and prior antimicrobial therapy (particularly with cephalosporins or aminoglycosides), perioperative antibiotic prophylaxis, prior surgical procedures, and longer hospitalization. All highly resistant strains appeared to be nosocomial since 12 cases were clustered on a surgical floor and in a burn unit. In vitro transfer of gentamicin resistance by filter mating was observed for 44 of 48 isolates. The use of plasmid content as an epidemiological marker suggested nosocomial transmission and exogenous acquisition of S. faecalis. PMID- 3084670 TI - Temporal relationships among immunologic alterations in a guinea pig model of thermal injury. AB - Temporal relationships among various humoral and cellular alterations of host defense mechanisms were investigated in a guinea pig model of thermal injury during three weeks after burning. Reduction in serum concentration of C3 and fixation of C3 on Pseudomonas aeruginosa, presence of activated C3 in plasma, and elevations in levels of 6-ketoprostaglandin F1 alpha and thromboxane B2 in wound fluid were observed at 3-6 hr after burning. These alterations were accompanied by reduction in intrinsic bactericidal activity of polymorphonuclear neutrophils (PMNs) against P. aeruginosa, suppression of bactericidal activity of PMNs by serum, and decreased blood clearance of P. aeruginosa. All parameters returned to normal values by seven to nine days after burning. Proliferative responses of splenic lymphocytes to T cell mitogens were depressed at four days after burning and were maximally reduced at eight days. These data support the concept that there is a continuum of immunologic alterations resulting from thermal injury and that consumption of complement and increase in arachidonic acid metabolism are early events. PMID- 3084671 TI - Newer data on the inactivation of scrapie virus or Creutzfeldt-Jakob disease virus in brain tissue. PMID- 3084672 TI - Bacillus cereus: a snake in the grass for granulocytopenic patients. PMID- 3084673 TI - Effects of recombinant human leukocyte interferon treatment of endogenous interferon production in patients with chronic type-B hepatitis. AB - Interferon (IFN) added to cell culture systems alters the capacity of the cells to produce IFN when appropriately stimulated. To evaluate the effects of in vivo administration of IFN on the production of IFN by peripheral blood mononuclear cells (PBMCs), we studied patients with chronic type-B hepatitis who received doses of recombinant human leukocyte (alpha) IFN (IFN-alpha) ranging from 5 X 10(6) units daily to 60 X 10(6) thrice weekly. The production of endogenous IFN stimulated by specific inducers (Sendai virus for IFN-alpha; phytohemagglutinin for IFN-gamma) was studied in cell cultures containing PBMCs obtained from patients before or during courses of IFN treatment. In untreated controls, no change in the mean capacity of PBMCs to produce IFN-alpha was noted after 2 weeks. Priming of endogenous IFN-alpha production, as reflected by earlier production of IFN by PBMCs in culture, occurred in all treated patients irrespective of the dose of IFN-alpha received. Whereas mean 24-hour (total) endogenous IFN-alpha fell in all treatment groups, the response was highly variable in individual patients and half showed no change in total production. Individual variations in endogenous IFN-alpha production were unrelated to serum IFN levels achieved during treatment, changes in serum aminotransferase levels, reduction of hepatitis B virus replication during therapy, or the proportions of T and B lymphocytes in culture. In contrast to the changes in IFN-alpha production, IFN-gamma production by PBMCs was not affected by IFN-alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084674 TI - Primary structural repeats in human and in murine gamma-interferon. AB - The Sellers TT algorithm has been used to conduct a detailed pattern search in the amino acid sequence of human and murine gamma-interferon. Each of these proteins contains two large repeats at the level of the primary amino acid sequence that divide each of these molecules into an aminoterminal and a related carboxyterminal segment. PMID- 3084675 TI - Neuro-endocrine disorders in obesity. PMID- 3084676 TI - Phosphatidylcholine, choline and cholinergic function. PMID- 3084677 TI - Statistical evaluation of nutritional, neurochemical and behavioural data: a case study. PMID- 3084678 TI - Food, mood and health: the Medieval outlook. PMID- 3084679 TI - Behavioural responses of rats on high- and low-protein diets, as a function of period of weaning. PMID- 3084680 TI - [PGF synthetase]. PMID- 3084681 TI - [Prostaglandin biosynthesis by pregnant myometrium]. AB - In order to study prostanoid biosynthesis, pregnant myometrium was taken from eleven patients undergoing cesarean section. Homogenates of myometrium were incubated with 14C labelled arachidonic acid and biosynthetic products were studied using silicic acid column chromatography, thin layer chromatography and gas-liquid chromatography. There were two metabolites assumed to be 12-hydroxy 5,8,10-heptadecatrienoic acid (HHT) or hydroxy acid. Concerning the prostaglandins, pregnant myometrium produced 6-keto PGF1 alpha, PGF2 alpha and PGE2. But the conversion rates to each prostaglandin has no relation to the gestational week. Moreover, the conversion rate to each prostaglandin was not higher in the samples taken from the patients with pains than that from the patients with no pains. The total conversion rate to prostaglandins also has no relation to the gestational week or pains. However the PGE2/PGF2 alpha (p less than 0.001) and 6-keto PGF1 alpha/PGF2 alpha (p less than 0.05) ratios were significantly higher in the patients with pains. PMID- 3084683 TI - [A study on the antibacterial activity of amniotic fluid--the significance of intraamniotic transferrin]. AB - In order to study the antimicrobial activity of amniotic fluid, attempts were made to evaluate the in vivo growth of bacteria in amniotic fluid and the role of transferrin in antibacterial activity. The bacteria chosen for these experiments were Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus faecalis, respectively. The results obtained were as follows: Amniotic fluid was shown have an antibacterial effect on Escherichia coli and Staphylococcus aureus, while Pseudomonas aeruginosa and Streptococcus faecalis proliferated readily in amniotic fluid. Individual difference in each sample appeared to be responsible for the inconsistent potency of the inhibitory effect observed. When amniotic fluid was heated at 100 degrees C for 5 minutes, the antibacterial activity was lost. The level of transferrin in amniotic fluid obtained at term was determined to be 29.1 +/- 17.6mg/dl (N = 90). The value correlated with neither those measured in cord sera nor maternal sera. The antimicrobial activity was restored by adding transferrin into heat-treated amniotic fluid at a concentration of 250mg/dl or higher. Simultaneous addition of transferrin and a sufficient concentration of iron made it possible to form a transferrin-iron complex. A subsequent decrease in unbound transferrin resulted in the loss of antibacterial properties. PMID- 3084682 TI - [Studies on plasma proteins in normal pregnancy and gynecological malignancy]. AB - The purpose of this study is to know and compare the changes in plasma proteins in normal pregnancy with those in gynecological malignancies. The results obtained are as follows. Factor VIII activity continued to increase during pregnancy and reached about 200%. It also continued to increase and showed a high level (250-300%) in malignancy, in advanced stages. At III activity increased in the first trimester and showed reached a normal level after 28 weeks of gestation. It decreased on the third day of puerperium and recovered to normal 1 month after delivery. At III activity decreased only in the end stage of malignancy. Factor XIII activity continued to decrease and was 50-60% during the second and third trimester. It began to recover at the third day of puerperium and completely recovered at 1 month after delivery. Factor XIII activity also continued to decrease and was at a low level (33.8-51%) in advanced stages. Plasminogen activity increased from the first trimester and was 120-130% during the second and third trimesters and after delivery. In malignancy, it did not show any remarkable change. alpha 2-PI activity moderately increased in the first trimester, but was at a normal level during the second and the third trimester. It increased slightly on the third day of the puerperium and recovered to normal 1 month after delivery. alpha 2-PI activity showed no remarkable change in malignancy, but decreased in some advanced cases. HRG began to decrease from the second trimester and was 46.5% at the end of the third trimester. In the puerperium, HRG began to recover on the third day and reached normal at 1 month. HRG showed a low titer in advanced stages of malignancy. Sialic acid increased constantly during pregnancy, but it was within the normal range. On the third day of puerperium, it reached 72.3mg/dl. Sialic acid showed a high level with in advanced stages of malignancy. IAP did not change during pregnancy. It showed a slight increase on the third day after delivery, but it was within the normal range. Malignancy showed a high level of HRG with in advanced stages. CIG was normal during and after pregnancy. In cervical carcinoma, CIG increased at in Ib, II and cervical carcinoma. Ovarian carcinoma did not show any change. PMID- 3084684 TI - [Study of the correlation between gonadotropin- and prolactin-releasing systems in women in the luteal phase and early pregnancy]. AB - The purpose of this study was to investigate the correlation between gonadotropin (Gn) and prolactin (PRL) releasing activities on the hypothalamo-pituitary axis in the luteal phase of the normal menstrual cycle and in the early gestational period. The plasma levels of LH-beta subunit (LH-beta) following an intravenous bolus of 100 micrograms LHRH did not change significantly in early pregnancy. The plasma PRL levels, as well as the Gn levels, were significantly elevated (p less than 0.05) after the administration of 100 micrograms LHRH in the luteal phase, but did not rise in early pregnancy. The intravenous bolus of 10mg metoclopramide (MCP) had no effect on plasma LH-beta, LH, FSH, estradiol or progesterone in the luteal phase or early pregnancy. The plasma PRL levels remained significantly (p less than 0.001) elevated after the administration of MCP. However, there was no significant difference between PRL response to MCP in the early pregnant and luteal phase groups. In the luteal phase, we could show the correlation between Gn and PRL releasing mechanisms on hypothalamo-pituitary axis, which could not be found in early pregnancy. PMID- 3084685 TI - Histologic origin of rat ovarian cancer induced by direct application of 7,12 dimethylbenz(a)anthracene. AB - A direct application of 7,12-dimethylbenz(a)anthracene (DMBA) to the ovary successfully produces an ovarian epithelial cancer in rat. To identify the histogenic process, the DMBA-treated rats were serially examined from the 15th to the 40th week following DMBA application. Furthermore, from the anticipated effect of estrogen on surface epithelial proliferation, the rats were put into an hyperestrogenic condition for immunohistochemical characterization of the tumor tissue. At the 20th week, the surface epithelial proliferations were seen to show remarkable multistratification with cellular pleomorphism. The proliferated surface cells began to infiltrate into the stroma to then form irregular gland structures. In immunoperoxidase stainings, both the adenocarcinoma cell and the surface cell has the same character in the immunohistochemical reaction for estradiol. On the base of these results, the induced cancer in rat was believed to have a similar histogenic process to the common epithelial tumors in human ovary. PMID- 3084686 TI - [Cancer chemotherapy against human tumor cell lines transplanted in nude mice. 1. The effect of a new anti-cancer agent, UFT]. PMID- 3084688 TI - [Clinical experience with high dose rate afterloading interstitial radiation--a preliminary report]. PMID- 3084687 TI - [Changes in cancer associated cellular proteins after administration of antitumor agent using 2-dimensional PAGE--index of efficacy of antitumor agents]. PMID- 3084689 TI - [Postpartum factor VIII inhibitor associated with primary biliary cirrhosis: a case report]. PMID- 3084690 TI - Antiestrogenic effect of clomiphene citrate in a multiple follicular stimulation protocol. AB - End-organ antiestrogenic effects of clomiphene citrate (CC) have been demonstrated in the female reproductive tract at the levels of the ovary, cervix, and endometrium. However, it has not been established whether this effect is manifested during concomitant human menopausal gonadotropin (hMG) administration, as occurs in hMG/CC stimulations of multiple follicular development. To assess this question a review was made of serum estradiol (E2) and cervical mucus in 47 hMG and 56 hMG/CC stimulations on days -2, -1, 0, and +1 relative to the day of hCG administration. E2 levels (pg/ml) were significantly lower in the hMG as compared to the hMG/CC group. However, comparing the hMG and hMG/CC groups, cervical mucus scores were significantly higher in the former. Furthermore, an analysis of covariance demonstrated that the cervical mucus scores on each day were significantly lower in the hMG/CC group (P less than 0.001). Thus, in hMG/CC stimulations for in vitro fertilization (IVF), despite the concomitant administration of pharmacologic doses of hMG, CC exerts an antiestrogenic effect on at least one end organ, cervical mucus production. Potentially, this antiestrogenic effect in IVF stimulations would be exerted at other female reproductive tract sites including the endometrium; however, its clinical significance, if any, is unclear. PMID- 3084691 TI - Antihemophilic factor [factor VIII] preparations inhibit lymphocyte proliferation and production of interleukin-2. AB - To examine the role of antihemophilic factor (factor VIII) preparations in the pathogenesis of subclinical immunodeficiency in hemophilia, we tested the in vitro effects of these products on immune function. Both lyophilized antihemophilic factor (LAHF) and cryoprecipitates inhibited lymphocyte proliferation in a dose-dependent fashion. Further studies indicated that LAHF interfered with an early event in proliferation and also that prolonged incubation of human lymphocytes with LAHF resulted in an irreversible inhibition of lymphocyte proliferation without detectable cytotoxic effects. LAHF also inhibited the production of interleukin-2 (IL-2) by human lymphocytes and by Jurkat tumor cells, suggesting that inhibition of IL-2 production was not mediated through effects on interleukin-1. Gel filtration of LAHF revealed two peaks of inhibitory activity; one with mol wt greater than 2 X 10(6) comigrated with factor VIII coagulant activity and antigen, whereas another with mol wt approximately 6 X 10(5) was devoid of factor VIII activity and antigen. Further study will ascertain whether administration of factor VIII-containing preparations contributes to the subclinical immunodeficiency seen in patients with hemophilia or serves as a cofactor in the development of clinical immunodeficiency after exposure to the retrovirus human T-lymphotropic virus type III. PMID- 3084692 TI - Specificity of gonadotrophin-releasing hormone binding sites of the human corpus luteum: comparison with receptors of rat pituitary gland. AB - The effects of a number of analogues of gonadotrophin-releasing hormone (GnRH) on the binding of a radiolabelled GnRH agonist (GnRH-A; [D-Ser(But)6, des Gly10]GnRH ethylamide) to homogenates of human corpus luteum (CL) and rat pituitary tissue were compared. Specific binding was inhibited by GnRH and GnRH-like peptides only. Both the C-terminal amide and N-terminal region of the GnRH molecule were required for binding in both tissues. However, amino acid substitutions at position 6 markedly enhanced, and at position 8 markedly reduced, binding potencies in rat pituitary tissue compared with human CL binding sites. These results indicate that GnRH-binding sites of rat pituitary and human luteal tissue have a similar degree of specificity for GnRH-like peptides, and a similar requirement for both N- and C-terminal regions of the peptide, but that differences in specificity related to the mid-chain region of GnRH exist between human luteal and rat pituitary binding sites. PMID- 3084693 TI - FSH-induced aromatase activity in porcine granulosa cells: non-competitive inhibition by non-aromatizable androgens. AB - The aim of this study was to examine the inhibitory effect of the non aromatizable androgens on FSH-stimulated aromatase activity in porcine granulosa cells. The cells were isolated from medium-sized follicles (4-6 mm) of prepubertal pigs, and cultured under chemically defined conditions in the presence of FSH (1 microgram/ml, NIADDK-oFSH-S13) with and without the androgens for an initial 48-h induction period. Subsequently, the spent medium was replaced with fresh medium containing only testosterone as substrate and the cells were reincubated for a further 6 h. The conversion of this steroid to oestradiol-17 beta during this latter 'test' period was taken as a measure of the aromatase activity. The addition of 5 alpha-dihydrotestosterone (DHT) into cultures of FSH stimulated cells during the induction period resulted in a definite dose dependent inhibition (30-70%) of the aromatase activity expressed in the test period. This inhibitory action, of the mixed non-competitive type, is characterized by a decrease in the apparent Vmax and an increase in the Km value, suggestive of an androgen inhibition of FSH-stimulated aromatase synthesis. This inhibition was also shown by the other 5 alpha- and 5 beta-reduced androgens: 5 beta-androstanedione was the most effective, while DHT was the least. Other steroids such as pregnenolone and progesterone were inhibitory, but testosterone and diethylstilboestrol were stimulatory. These results suggest an important mechanism for the intrafollicular control of oestrogen synthesis, involving a possible reciprocal relationship between aromatase and 5 alpha-reductase activities. PMID- 3084694 TI - Ontogeny of serum and pituitary gonadotrophins in male rats treated with low doses of 5 alpha-dihydrotestosterone. AB - The effect of s.c. daily injections of 10 or 1000 ng 5 alpha-dihydrotestosterone (DHT)100 g body weight from birth to day 21, or from days 26 to 117 of age, on the changes in concentration of serum and pituitary gonadotrophins was investigated in male rats. Treatment with 10 ng DHT from days 1 to 21 depressed serum FSH, but not LH, at day 7, while 1000 ng DHT depressed both serum LH and FSH. Treatment with both doses of DHT reduced pituitary levels of LH and FSH at day 7, with FSH being more depressed than LH. Treatment with 10 ng DHT from days 26 to 117 increased serum FSH from days 82 to 117, while 1000 ng DHT did not have this effect. Treatment with 1000 ng, but not 10 ng, DHT between days 26 and 117 reduced pituitary levels of LH and FSH at day 40. Rats treated with the two doses of DHT from days 26 to 117 showed a difference in the responsiveness of the pituitary to LH-releasing hormone (LHRH). Treatment with 10 ng DHT enhanced LHRH induced release of LH without affecting FSH release, while 1000 ng DHT depressed LHRH-induced release of FSH but not of LH. These findings support the view that DHT may play a modulatory role in the ontogeny of serum gonadotrophins and the responsiveness of the pituitary to LHRH during the onset of puberty in the male rat. PMID- 3084695 TI - Stimulation of in-vivo growth hormone secretion in young chickens by rat hypothalamic growth hormone-releasing factor and synthetic analogues. AB - Rat hypothalamic GH-releasing factor (rhGRF), at doses between 0.1 and 10 micrograms/kg, increased plasma GH concentrations in immature domestic fowl 5-10 min after i.v. injection. Sodium pentobarbitone anaesthesia blunted the GH responses to rhGRF, although in both conscious and anaesthetized chicks the maximal responses were induced by a dose of 1 microgram rhGRF/kg. The stimulatory effect of rhGRF on in-vivo GH secretion was less than that provoked by corresponding doses of human pancreatic GRF, but greater than that elicited by two rhGRF analogues, (Nle27)-rhGRF(1-32) and (Nle27)-rhGRF(1-29). These results demonstrate that the chicken pituitary is responsive to mammalian GRF and provide evidence of structure-activity relationships of GRF in the domestic fowl. PMID- 3084696 TI - Melanocyte-stimulating hormone, tyrosinase activity and the regulation of eumelanogenesis and phaeomelanogenesis in the hair follicular melanocytes of the mouse. AB - Skin tyrosinase levels and the eumelanin and phaeomelanin contents of the hair were measured in pubertal and adult C3H-HeA*vy mice that grow dark and golden yellow hair respectively. Hair growth was initiated by plucking and the skin tyrosinase levels, which increased during the growth of new hair and peaked at around 9 days after plucking, were higher during the growth of dark hair in the pubertal mice than during the growth of yellow hair in the adult mice. Although there was only a twofold difference in the phaeomelanin contents of these two types of hair, the dark hair of the pubertal mice contained over 20 times more eumelanin than the golden-yellow hair of the adult mice. These results suggest that the changes in coat colour in C3H-HeA*vy mice are due mainly to changes in eumelanin synthesis by the hair follicular melanocytes and that the production of this pigment requires higher levels of the enzyme tyrosinase than does the production of phaeomelanin. These changes did not appear to be related to plasma alpha-MSH levels. Nevertheless, administration of alpha-MSH increased skin tyrosinase activity in the pubertal mice that were growing dark hair and produced a twofold increase in the eumelanin content of the hair. However, it had no such effects in adult mice and also failed to affect the phaeomelanin content of the hair in both groups of mice. In contrast to alpha-MSH, bromocriptine decreased skin tyrosinase levels and the eumelanin content and increased the phaeomelanin content of the hair in pubertal mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084697 TI - Involvement of protein kinase C in mouse mammary gland development. AB - The relationship between kinase C activity and mammary gland differentiation was investigated by following kinase activity throughout the mouse reproductive cycle and by pharmacologically perturbing the kinase, while monitoring biochemical differentiation. Protein kinase C activity declined during pregnancy and remained low throughout lactation, suggesting an inverse relationship with milk protein expression. This negative association was further supported by the use of quercetin (50-100 mumol/l) and gossypol (50 mumol/l), which are both protein kinase C inhibitors. These compounds doubled alpha-lactalbumin levels in mammary explants cultured with hormones. However, a phorbol ester, known to activate protein kinase C, had no effect on alpha-lactalbumin production, although it did stimulate this milk protein 2.5-fold in the presence of the calcium ionophore, A23187. In the absence of raised calcium levels, protein kinase C activity therefore appeared to be inversely correlated with biochemical differentiation; but, in the presence of increased calcium concentrations, both calcium and the kinase acted synergistically to augment hormone-induced alpha-lactalbumin expression. PMID- 3084698 TI - Synergistic interaction in bovine pituitary cultures between growth hormone releasing factor and other hypophysiotrophic factors. AB - Synthetic human pancreatic GH-releasing factor (1-44)NH2 (GRF) and acetylcholine (ACh) were shown to evoke a dose-related release of GH from cultured bovine pituitary cells with half-maximal effective doses of 0.3 and 500 nmol/l respectively. Concentrations of ACh (10 mumol/l) and GRF (25 nmol/l) which were shown to give near maximal responses when presented alone, produced highly synergistic responses when tested in combination. This synergism was related to the ACh concentration employed, and both the ACh-induced release and ACh-induced synergism were abolished by the muscarinic antagonist, atropine. A synergistic interaction was also demonstrated between GRF and concentrations of thyrotrophin releasing hormone (TRH) and bombesin which, in the absence of GRF, failed to elicit significant GH release. Acetylcholine stimulated a similar dose-dependent release of prolactin, but GRF was ineffectual in either directly stimulating prolactin release or affecting the response to ACh or TRH. No synergistic interaction could be detected between combinations of ACh and TRH or between ACh and bombesin. The data suggest that, in the somatotroph, GRF acts through a different second messenger pathway to ACh, TRH and bombesin and that these two pathways can be activated to produce a potentiated response. Growth hormone releasing factor is, therefore, not only a specific GH secretagogue, but may act in concert with other hypophysiotrophic factors to regulate GH secretion from the bovine anterior pituitary. PMID- 3084699 TI - Differential expression of sets of highly homologous variable region gene products in selected and preimmune repertoires of inbred mouse strains. AB - Using mAb that selectively recognize the various allelic forms of the VHT15 and Vk21D-E genes' products, we analyzed the influence of VH and Vk polymorphism on the probability of expression of these gene segments. Our data show that the frequency to which the VHT15 gene product becomes available in the preimmune repertoire is strongly influenced by the polymorphism of the relevant structural gene, suggesting therefore that VH genes cannot be randomly used in the various strains. Contrary to this, the frequency of Vk21D-E+ clones is similar in all mouse strains tested, and in all cases is higher than the frequency of VHT15 clones. This observation strongly suggests that Vk genes can be randomly expressed, and/or that their number is lower than that of their VH counterpart. Finally, analysis of the specificity associated to the expression of the VHT15 segment revealed that VH polymorphism strongly influences not only the probability of expression of each V gene, but also the specificity of the antibodies on which these VH genes are used. PMID- 3084701 TI - Interleukin 1 and lipopolysaccharide induce an inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells. AB - Human IL-1, recombinant murine IL-1 and E. coli LPS were found to be potent inducers of plasminogen activator (PA)-inhibitor activity, both in vivo, in rats, as well as in cultured human endothelial cells. In vivo, LPS rapidly and dose dependently (0.01-1,000 micrograms/kg) increased plasma PA-inhibitor activity. Infusion of IL-1 into rats resulted in a small but significant increase in PA inhibitor activity in rat plasma. Likewise, in cultured human umbilical vein endothelial cells, LPS and IL-1 induced increased synthesis of PA-inhibitor. We suggest that the induced rat plasma inhibitor might be of endothelial origin. PMID- 3084700 TI - Antigen-driven long term-cultured T cells proliferate in vivo, distribute widely, mediate specific tumor therapy, and persist long-term as functional memory T cells. AB - Mice bearing disseminated syngeneic FBL-3 leukemia were treated with cyclophosphamide plus long term-cultured T cells immune to FBL-3. The cultured T cells for therapy had been induced to grow in vitro for 62 d by intermittent stimulation with irradiated FBL-3. At the time of therapy, such antigen-driven long term-cultured T cells were greatly expanded in number, proliferated in vitro in response to FBL-3, and were specifically cytotoxic. Following adoptive transfer, donor T cells persisting in the host were identified and counted using donor and host mice congenic for the T cell marker Thy-1. The results show that antigen-driven long term-cultured T cells proliferated rapidly in vivo, distributed widely in host lymphoid organs, and were effective in tumor therapy. Moreover, the already rapid in vivo growth rate of donor T cells could be augmented by administration of exogenous IL-2. When cured mice were examined 120 d after therapy, donor L3T4+ T cells and donor Lyt-2+ T cells could be found in large numbers in host ascites, spleen, and mesenteric and axillary lymph nodes. The persisting donor T cells proliferated in vitro, and became specifically cytotoxic in response to FBL-3, demonstrating that antigen-driven long term cultured T cells can persist long term in vivo and provide immunologic memory. PMID- 3084702 TI - Excitatory conditioning of individual Drosophila melanogaster. AB - Testing individual animals from a heterogenic population of Drosophila melanogaster, we demonstrate conditioning of the proboscis extension reflex. The presentation of paired (conditioning) stimuli produced (a) an increase in the average number of conditioned responses over trials, (b) measured differences in performance levels among individual subjects, and (c) a sex difference, with more males conditioned than females, and those that did did so more quickly. The presentation of unpaired (control) stimuli produced significantly lower average levels of acquisition responding and a change in the distribution of individual response patterns. Neither central excitatory state nor sensitization induced by the conditioned or unconditioned stimuli directly affected the conditioned response, whereas unconditioned stimulus preexposure adversely affected performance levels. Presenting the unpaired (extinction) stimuli after conditioning produced less of a decline in responding than did an extinction procedure with removal of the unconditioned stimulus. With the ability to identify individual differences in acquisition and extinction patterns, and given the relatively large number of individuals that can be tested simultaneously on the automated stimulation apparatus, it is now possible to make precise behavioral measurements on samples large enough for the behavior-genetic analysis of D. melanogaster with conditioning as the phenotype. PMID- 3084703 TI - Development of the eye-antenna imaginal disc and morphogenesis of the adult head in Drosophila melanogaster. AB - We have studied the organization and development of the eye-antenna imaginal disc of Drosophila melanogaster. We examined the pattern of gynandromorph mosaicism and determined the "sturt distances" between 42 different structures of the head, antenna, and maxillary palpus. A morphogenetic map based on these sturt distances resembles more closely in size and shape that of a single thoracic segment than that of two or more adjacent segments, suggesting that the eye-antenna disc is derived from a single embryonic body segment. We examined the morphology of the eye-antenna discs in situ in late third-instar larvae in serial cross sections. The two discs are connected medially by a thin cellular membrane that probably serves to join the two discs during evagination and morphogenesis of the adult head. A fate map of the imaginal disc was established by cutting the mature disc into fragments and transplanting the fragments into host larvae for metamorphosis. The peripodial layer of the eye-antenna disc is thickened in several regions, and our data suggest that these thickened areas represent primordia of adult head structures. A comparison of the location of precursors in the imaginal disc with those of the differentiated structures of the adult head revealed the nature of the morphogenetic movements that must occur during evagination and differentiation. PMID- 3084704 TI - Presence of sucrase in the yolk sac of the chick. AB - The presence of sucrase in the yolk sac of the chick was studied biochemically and immunologically. The sucrase was partially purified from the yolk sac of hatched chicks and was compared with the sucrase purified from the small intestine. Immunodiffusion with antiserum against intestinal sucrase and characterization of the activity revealed that the two enzymes were almost identical. However, the size of the yolk sac sucrase was found to be slightly smaller than that of the intestinal enzyme by chromatography on Sephadex G-200 and polyacrylamide gel electrophoresis. Immunocytochemical studies showed that the sucrase was located on the free surface of yolk sac endodermal cells, but the sucrase may also be present in the cytoplasm. PMID- 3084705 TI - Conventional and multiple-monitored electroconvulsive therapy. A comparison in major depressive episodes. AB - In retrospective and anecdotal reports, multiple-monitored electroconvulsive therapy (MMECT), a procedure in which a number of seizures are induced within a single treatment session, has been noted to be as effective more rapidly than conventional electroconvulsive therapy (CECT). However, several studies have reported an increased risk of very long seizures and prolonged confusional states with the multiple procedure. The present study investigated CECT and MMECT in a prospective, single-blind protocol measuring a number of variables within three general areas of concern: efficacy, safety, and efficiency of treatment. Results indicate that CECT and MMECT were equally effective in 54 patients with a major depressive episode; the treatments differed, however, in persistence of side effects and in efficiency as measured by cost-effectiveness and the utilization of staff and physician time. PMID- 3084706 TI - Differential effects of apomorphine on spinal reflex activity following 6 hydroxydopamine or long-term haloperidol pretreatment. AB - The thermal cutaneous evoked tail flick response was measured both before and after intrathecal injection of R-apomorphine in spinal rats and in rats with an intact neuraxis pretreated with either long-term haloperidol or intrathecal 6 hydroxydopamine. Intrathecal R-apomorphine produced a dose-dependent increase of tail flick latency in spinal rats but not in intact rats. Long-term haloperidol treatment increased the effect of R-apomorphine in spinal rats while 6-OHDA decreased it. The present findings provide further evidence for the modulatory role of spinal DA receptor populations on spinal reflex activity. Pretreatment with long-term haloperidol or 6-OHDA may alter the conformational status of spinal DA receptors in opposite directions and thereby change the responsiveness of receptors to R-apomorphine. PMID- 3084707 TI - Characterization of protein-bound gold in rat urine following aurothiomalate administration and of rat and human albumin-gold-thiomalate. AB - The metabolites of gold in the urine of rats given the antiarthritic drug aurothiomalate were investigated by gel permeation chromatography, electrophoresis, and chemical studies. Following a single dose of aurtothiomalate, the excreted gold was protein-bound in the high-molecular-weight (greater than or equal to 150,000 dalton) and serum albumin fractions. Electrophoresis confirmed the presence of albumin, but showed that the other proteins present differ from those in normal or in vitro aurothiomalate-incubated rat sera. The pattern of the proteins establishes that the proteinuria was of the glomerular type. The alterations in the gold distribution produced by incubation of the urine with the low-molecular-weight thiol penicillamine and with exogenously added aurothiomalate indicated the existence of a labile equilibrium of gold among protein binding sites in the urine. Incubation of rat and human sera and commercially prepared serum albumins with aurothiomalate increased the electrophoretic mobility of the albumin. The significance of this change in electrophoretic mobility with respect to two models of gold binding by serum albumin is discussed. PMID- 3084708 TI - Cerebrovascular permeability coefficients to sodium, potassium, and chloride. AB - CSF and regional brain concentrations of 42K, 22Na, 36Cl, and [14C]mannitol were determined 3-45 min after intravenous injection of the tracers in pentobarbital anesthetized rats. Rapid influx of 36Cl and 22Na into ventricular CSF immediately established concentration gradients from CSF to brain extracellular fluid. The CSF contribution to brain uptake of tracers was greatest in periventricular brain regions, where brain 36Cl concentrations were up to ninefold higher than concentrations in regions distant from ventricular CSF. Acetazolamide (20 mg kg-1 i.p.), an inhibitor of CSF formation, decreased 36Cl uptake into CSF and into periventricular brain regions but not into frontal cortex. 36Cl uptake into brain was unidirectional for 10 min after intravenous injection, and, during that period, diffusion from ventricular CSF did not contribute to uptake in the frontal cortex. Therefore, cerebrovascular permeability coefficients could be calculated from tracer concentrations in frontal cortex at 10 min and equaled, in cm s-1, 13.5 X 10(-7) for 42K, 1.4 X 10(-7) for 22Na, 0.9 X 10(-7) for 36Cl, and 1.5 X 10(-7) for [14C]mannitol. The low cerebrovascular permeabilities to K, Na, and Cl, comparable to those of some cell membranes, and the permselectivity (K much greater than Na greater than Cl) suggest that a significant fraction of ion transport across cerebral capillaries is transcellular, i.e., across the endothelial cell membrane. PMID- 3084709 TI - Cross-linking of neurofilament proteins of rat spinal cord in vivo after administration of 2,5-hexanedione. AB - The aliphatic hexacarbons n-hexane, methyl-n-butyl ketone, and 2,5-hexanedione are known to produce a peripheral neuropathy that involves an accumulation of 10 nm neurofilaments above the nodes of Ranvier in the spinal cord and peripheral nerve. In this study, rats were treated with 0.5% 2,5-hexanedione in drinking water for 180 days, and their spinal cord neurofilaments were isolated after development of the neuropathy. Visualization by sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a significant reduction in content of the neurofilament triplet proteins in treated animals and the presence of bands migrating at 138K and 260K that were not present in control animals. Analysis of the lanes using immunoblotting procedures and anti-70K, anti-160K, and anti-210K neurofilament antibodies revealed many cross-linked peptides. The 138K band cross reacted with the anti-160K neurofilament antibody. This suggests that the 138K band is an intramolecular cross-link of the 160K neurofilament subunit. In addition to this peptide, there were numerous high-molecular-weight peptides immunoreactive with all three neurofilament protein antibodies. In addition to cross-linking, there was also a diminished amount of immunoreactive breakdown product of all three neurofilament proteins. This report demonstrates direct evidence of 2,5-hexanedione-induced cross-linking of neurofilament proteins in vivo, which maybe responsible for the accumulation of neurofilament proteins pathognomic of this neuropathy. PMID- 3084710 TI - A mass spectrometric method for the identification of novel peptides in Xenopus laevis skin secretions. AB - The peptides secreted by the South African frog Xenopus laevis were screened systematically using a strategy based on fabms. Hplc of crude and Sephadex G-10 chromatographed secretions showed that many more peptides were present in these secretions than those previously identified, i.e., xenopsin, caerulein, TRH, and PGLa. Fractions from the hplc were analyzed directly by fabms to determine the molecular weights of these novel peptides. Subsequent analyses, using a combination of fabms, manual Edman degradation, enzymatic digestions, and amino acid analyses identified the partial and sometimes complete sequences of these peptides which had molecular weights ranging from 700-2700. Many peptides with structural features that are often indicative of biological activity, e.g., C terminal amides and pyroglutamic acid, were readily identified by fabms. In some cases, molecular weight data combined with partial sequence data was sufficient to identify peptides as originating from spacer regions in the precursors to xenopsin, caerulein, and PGLa. PMID- 3084712 TI - Valproate causes metabolic disturbance in normal man. AB - Valproate is an important anticonvulsant which is rarely associated with fatal hepatotoxicity. Previous experiments have shown that valproate inhibits several metabolic processes in isolated rat hepatocytes and when administered to starved rats causes a fall in the blood concentrations of glucose and ketone bodies. Since these changes may be related to the hepatotoxicity, the effect of valproate administration on intermediary metabolism in man was studied. One gram of valproate given orally to fasted normal humans caused a 78% fall in the concentration of 3-hydroxybutyrate and a 60% fall in total ketones. Also the concentrations of lactate, pyruvate, alanine and glycerol increased after valproate administration. Similar changes were observed after intravenous administration of 400 mg of valproate. Valproate clearly has a significant effect on intermediary metabolism in the liver and this is probably related to the mechanism of the hepatotoxicity. PMID- 3084711 TI - Inherited multiple meningiomas: a clinical, pathological and cytogenetic study of an affected family. AB - The clinical features of a family with inherited multiple meningiomas as the major manifestation of neurofibromatosis are presented. The value of noninvasive radiological screening investigations is emphasised. The results of cytogenetic and pathological studies on the family are presented and discussed with a review of the relevant literature. PMID- 3084713 TI - Seizures triggered by blinking in a non-photosensitive epileptic. AB - An epileptic girl with Lennox-Gastaut syndrome had seizures triggered specifically by blinking, but not by other eye movements or by photic stimulation. Electrographic and clinical seizures were most reliably precipitated by repetitive blinking produced voluntarily on command, by reflex blinking on corneal stimulation, or by psychogenic triggers of blinking such as social stress or cognitive effort. PMID- 3084714 TI - Effect of L-threo-3,4-dihydroxyphenylserine chronic administration on cerebrospinal fluid and plasma free 3-methoxy-4-hydroxy-phenylglycol concentration in patients with Parkinson's disease. AB - L-Threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was administered as a means of treating akinesia in 9 patients with Parkinson's disease and one with pure akinesia. Akinetic symptoms were improved in 7 of 10 patients. During chronic L threo-DOPS treatment, cerebrospinal fluid (CSF) and plasma concentrations of free 3-methoxy-4-hydroxyphenylglycol (MHPG) and L-threo-DOPS were measured in these 10 patients. The results show that there were no significant changes in either CSF or plasma free MHPG concentrations before or during L-threo-DOPS administration. The L-threo-DOPS concentration during treatment was not measurable in the CSF of 2 patients nor in the plasma of 1 out of 4 patients given only L-threo-DOPS. It was, however, measured in all patients treated with a combination of L-threo-DOPS and L-DOPA plus carbidopa. The results show that L-threo-DOPS is transported into the CSF, and suggest that its active mechanism may be further clarified by studying its action on not only noradrenaline, but also other neurotransmitters. PMID- 3084715 TI - Interval between the synthesis and assembly of cytoskeletal proteins in cultured neurons. AB - We have used pulse-chase experiments to study the time interval between the synthesis and assembly of tubulin and neurofilament proteins (NFP) in sympathetic neurons grown in tissue culture. After varying pulse-chase times, cultures were extracted with Triton X-100 such that polymerized tubulin and NFP were insoluble, while unassembled tubulin and NFP were quantitatively solubilized. The partitioning of labeled tubulin and NFP between Triton X-100-soluble and insoluble, or cytoskeletal, fractions was determined with an isoelectric focusing X SDS gel electrophoresis assay. Labeled tubulin and NFP in cultures pulse labeled for 5-10 min partitions primarily with the soluble fraction. When pulse labeled cultures were chased for increasing periods of time, relatively more of the total labeled tubulin and NFP partitioned with the cytoskeleton, attaining maximal values after chase times of 60-120 and 15-30 min, respectively. The maximal values for the relative levels of labeled tubulin and NFP in polymer were 70-75 and greater than 90%, respectively. The levels of labeled tubulin and NFP synthesized during a short pulse-label remained constant for at least 2 hr, indicating that selective turnover of soluble tubulin and NFP does not detectably contribute to the changes in solubility properties of these proteins observed in the pulse-chase experiments. These results indicate that newly synthesized tubulin and NFP are rapidly assembled from soluble precursors. The lag between the synthesis and assembly of the 145,000-molecular-weight NFP is not related to its phosphorylation because its initial incorporation into the cytoskeleton occurs prior to its phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084716 TI - Sensitization of the crayfish lateral giant escape reaction. AB - Most behavioral reactions that habituate can also be dishabituated by strong stimuli. In the best studied cases, dishabituation seems to be the result of an independent "sensitization" of the behavioral reaction that compensates for habituation without necessarily abolishing it. Crayfish lateral giant (LG) neuron mediated escape reactions are one of the most fully analyzed behavioral reactions that are prone to habituation; however, sensitization/dishabituation of LG escape has not previously been reported. Here, the effect of strong AC shocks to head or abdomen on the ability of 0.1 msec "test" shocks to sensory roots innervating the tailfan to elicit an LG escape response was examined. Following single AC shocks, test shock threshold for eliciting LG escape reliably fell 5-80% and recovered over 15 min to 1 hr. When AC shocks and test shocks alternated at 90 sec intervals, test shock threshold rapidly dropped to an asymptote that was maintained as long as AC shocks were given (up to 2 hr); following such repeated AC shocks, recovery often required a number of hours but was complete within 24. Comparable sensitization is seen in the response of interneuron A, the largest of a set of sensory interneurons that links afferents to LGs. AC shocks (to either head or tail) no longer sensitize abdominal LG reflex circuitry if the nerve cord is severed between thorax and abdomen. Thus, sensitization appears to depend on a neurally conducted influence that arises in the rostral half of the animal. Pharmacological evidence suggests that octopamine may mediate the sensitization. PMID- 3084717 TI - Demonstration of thyrotropin-releasing hormone immunoreactivity in neurons of the mouse spinal dorsal horn. AB - Thyrotropin-releasing hormone-like immunoreactivity was demonstrated in neurons within the superficial laminae (I, II, III) of the mouse spinal dorsal horn by light-microscopic peroxidase immunocytochemistry. The immunoreactivity was distributed in a narrow dorsoventral band that enclosed the substantia gelatinosa (lamina II), with a higher concentration along the lamina II/III border. At present, the functional significance of these neurons is unknown. Their existence within the substantia gelatinosa suggests a role in sensory information processing. PMID- 3084718 TI - Differential diagnosis of CT-hypodense cranial lesions with indium-111-oxine labeled leukocytes. AB - Scintigraphy using indium-111-oxine-labeled white blood cells was used as a complementary diagnostic study in the differential diagnosis of 20 intracerebral cystic lesions for which computerized tomography scanning did not exclude abscess. To lower the rate of false-positive findings with scintiscanning, three criteria of positivity were tested in the 20 lesions. The most stringent criterion yielded 100% sensitivity, 94% specificity, and 96% diagnostic accuracy. The clinical and surgical implications of these results are discussed. PMID- 3084719 TI - The effect of mannitol on cerebral blood flow. AB - The objective of this study was to evaluate the effects of mannitol, given over different time periods, on regional cerebral blood flow (rCBF) in patients with intracranial aneurysms. Seven patients with unruptured aneurysms (Group I) and 16 patients with Grade I and II subarachnoid hemorrhage (SAH) (Group II) received 1.5 gm/kg/8 hrs of 20% mannitol intravenously over a 24-hour period. Seven other patients with unruptured aneurysms (Group III) received 1.5 gm/kg of mannitol over 8 hours only. The last seven patients with unruptured aneurysms (Group IV) received the same dose, but as an intravenous bolus. Over a period of 24 hours, the patients underwent serial measurements of rCBF, intracranial pressure (ICP), mean blood pressure (MBP), cardiac output, and cerebral metabolic rate of oxygen consumption (CMRO2). Mannitol, when given as a continuous intravenous infusion, increased rCBF significantly without increasing MBP or decreasing ICP. This increase was more pronounced in SAH patients. The effects of mannitol lasted for 18 hours when given over an 8-hour period only; however, when it was given as a bolus, the increase in rCBF lasted for 24 hours, cardiac output tended to increase, and the effect on CMRO2 was variable. PMID- 3084720 TI - Cerebral effects of hypocapnia plus nitroglycerin-induced hypotension in dogs. AB - This study examined the effect of hypocapnia (PaCO2 20 mm Hg) on cerebral metabolism and the electroencephalogram (EEG) findings in 12 dogs during nitroglycerin (NTG)-induced hypotension. Previous studies suggest that NTG is a more potent cerebral vasodilator than sodium nitroprusside or trimethaphan. It was speculated that combining hypocapnia with NTG-induced hypotension would cause less disturbance of cerebral metabolism and the EEG than the disturbances previously reported when hypocapnia was combined with hypotension induced by sodium nitroprusside or trimethaphan. All 12 dogs were examined at 1) normocapnia with normotension; 2) hypocapnia with normotension; and 3) hypocapnia combined with NTG-induced hypotension to mean arterial blood pressure (MABP) levels of 60, 50, and 40 mm Hg. In six dogs the cerebral metabolic rate of oxygen was determined, and the EEG was evaluated using compressed spectral analysis. Brain tissue metabolites were calculated in the other six dogs. During normotension, hypocapnia caused no deterioration of cerebral metabolism or of the EEG. Hypocapnia combined with NTG-induced hypotension caused a decrease of the power of the alpha and beta 2 spectra of the EEG at MABP's of 60 mm Hg or less. At an MABP of 40 mm Hg, brain tissue phosphocreatine and the cerebral energy charge decreased, while the brain tissue lactate:pyruvate ratio increased. Thirty minutes after restoration of normocapnia with normotension, cerebral metabolites returned to initial values, but the power of the EEG alpha and beta 2 spectra was decreased compared to baseline values. The cerebral metabolic disturbances and EEG alterations seen here with hypocapnia plus NTG-induced hypotension were similar to those previously reported with hypocapnia plus sodium nitroprusside induced hypotension, and less than those previously reported with hypocapnia plus trimethaphan-induced hypotension. For hyperventilated patients, administration of NTG may be a better hypotensive treatment than trimethaphan, but similar in effect to sodium nitroprusside. PMID- 3084722 TI - Alimentation of head-injured patients. PMID- 3084721 TI - A pharmacological analysis of the pathophysiological mechanisms of posttraumatic spinal cord ischemia. AB - A pharmacological analysis was carried out to determine the possible role of aberrant calcium fluxes, vasoactive arachidonic acid metabolites, and microvascular lipid peroxidation in the development of posttraumatic spinal cord white matter ischemia. Pentobarbital-anesthetized cats were treated intravenously 30 minutes before a 500-gm-cm contusion injury to the lumbar spinal cord with one of the following test drugs: the Ca++ channel antagonists verapamil, diltiazem, or nifedipine; the cyclo-oxygenase inhibitors ibuprofen or meclofenamate; the thromboxane A2 (TXA2) synthetase inhibitor furegrelate sodium; or the stable epoprostenol (prostacyclin, or PGI2) analogue ciprostene calcium alone or in combination with furegrelate sodium. Another group of animals was pretreated for 5 days before spinal injury with a combination of the antioxidants vitamin E and selenium in high doses. The hydrogen clearance technique was used to make repeated measurements of spinal cord blood flow (SCBF) in the dorsolateral funiculus of the injured segment before and for 4 hours after injury. In 11 untreated uninjured cats, the mean preinjury SCBF was 12.7 +/- 1.5 ml/100 gm/min. Following contusion, there was a progressive decline in SCBF to 6.8 +/- 0.4 ml/100 gm/min, or 53.5% of the preinjury level at 4 hours. In comparison, the Ca++ antagonists diltiazem and nifedipine (but not verapamil) prevented a significant posttraumatic decrease in SCBF. Similarly, both cyclo-oxygenase inhibitors (ibuprofen and meclofenamate) maintained SCBF within normal limits (10 ml/100 gm/min or greater). However, neither TXA2 synthetase inhibition nor the stable PGI2 analogue alone had a significant effect in preventing ischemia, whereas a combination of the two agents did serve to support SCBF. The most impressive preservation of posttraumatic SCBF, however, was observed in the antioxidant-treated animals. Based upon these results, a hypothesis is presented concerning the pathogenesis of posttraumatic central nervous system ischemia which integrates an injury-induced rise in intracellular Ca++, the increased synthesis of vasoactive prostanoids (such as prostaglandin F2 alpha and TXA2), and progressive microvascular lipid peroxidation. PMID- 3084723 TI - RNs may cost less than you think. AB - The health care environment is in a new era. Hospital and nursing administrators will be faced with tough decisions regarding number and skill level of staff. Productivity of various levels of nursing personnel is one parameter upon which decisions can be made. In this research, productivity is defined as the percentage of time spent in direct care, indirect care, and unit-related activities. The research indicates that the higher the level of personnel, the higher the productivity. PMID- 3084724 TI - Harry Morton Vars (1903-1983). Biographical sketch. PMID- 3084725 TI - Effect of continuous and discontinuous intravenous or intragastric total parenteral nutrition in rats on serum lipids, liver lipids and liver lipogenic rates. AB - Lipogenesis and evidence of fat accumulation in the liver were investigated in adult male rats fed a hypertonic dextrose diet by continuous (C) and discontinuous (D) intravenous (IV) or intragastric (IG) infusion for 14 d. Rats fed by the IV and IG route were infused continuously and discontinuously (2100 0900) with 55 ml/d of a solution containing 30% dextrose and 2.72% amino acids plus vitamins and minerals. An orally (Or) fed group was fed 21.2 g of a solid diet, which provided an equivalent amount of calories and nitrogen as the infusion diet. Serum lipids, glucose, and insulin levels, de novo fatty acid synthesis in adipose tissue and liver, and the content of liver lipids were not altered by feeding the diet IV or IG. De novo lipogenesis was elevated in the livers of the continuously and discontinuously infused IV-or IG-fed rats compared with Or-fed rats. Fat accumulated in the livers of the rats infused continuously but not in the livers of the rats fed DIV, DIG or Or. Discontinuous feeding was associated with the mobilization of fatty acids that are necessary for lipoprotein formation and transport from the liver, which may explain, in part, why discontinuously infused rats do not develop fatty livers. These data indicate that cycling the total parenteral infusion may have clinical importance. PMID- 3084726 TI - epsilon-N-trimethyllysine availability regulates the rate of carnitine biosynthesis in the growing rat. AB - Rates of carnitine biosynthesis in mammals depend on the availability of substrates and the activity of enzymes subserving the pathway. This study was undertaken to test the hypothesis that the availability of epsilon-N trimethyllysine is rate-limiting for synthesis of carnitine in the growing rat and to evaluate diet as a source of this precursor for carnitine biosynthesis. Rats apparently absorbed greater than 90% of a tracer dose of [methyl-3H]epsilon N-trimethyllysine, and approximately 30% of that was incorporated into tissues as [3H]carnitine. Rats given oral supplements of epsilon-N-trimethyllysine (0.5-20 mg/d), but no dietary carnitine, excreted more carnitine than control animals receiving no dietary epsilon-N-trimethyllysine or carnitine. Rates of carnitine excretion increased in a dose-dependent manner. Tissue and serum levels of carnitine also increased with dietary epsilon-N-trimethyllysine supplementation. There was no evidence that the capacity for carnitine biosynthesis was saturated even at the highest level of oral epsilon-N-trimethyllysine supplementation. Common dietary proteins (casein, soy protein and wheat gluten) were found to be poor sources of epsilon-N-trimethyllysine for carnitine biosynthesis. The results of this study indicate that the availability of epsilon-N-trimethyllysine limits the rate of carnitine biosynthesis in the growing rat. PMID- 3084727 TI - Effect of starvation on the disposition of free and peptide-linked trimethyllysine in the rat. AB - Free and peptide-linked trimethyllysine were measured in fed and 5-d starved rats. The trimethyllysine content of liver and kidney was significantly increased on d 5 of starvation to two to three times the levels found in fed animals. Skeletal muscle of fed rats contained over six times as much trimethyllysine (19.3 nmol/g) as that found in liver (3.2 nmol/g) or kidney (2.7 nmol/g). Plasma free trimethyllysine significantly increased from 1 nmol/ml in fed rats to 2.2 nmol/ml in 5-d starved rats. During this same period, daily total trimethyllysine excretions averaged approximately 400 nmol/d. Urinary free trimethyllysine was significantly depressed during starvation. Assuming that trimethyllysine in plasma does not exist in a protein-bound form, clearance calculations based on concentrations of plasma and urinary trimethyllysine indicated that this compound is readily reabsorbed by the kidney. As previous studies have indicated that trimethyllysine is not readily absorbed by other tissues, this indicates that the kidney may be the primary regulatory site for the disposition free of free trimethyllysine in plasma and urine. Estimates of the efficiency of entry of trimethyllysine into the carnitine biosynthetic pathway were calculated and ranged from 41% in 3-d starved rats to 80% in fed rats. We conclude that carnitine biosynthesis is limited by the availability of trimethyllysine, which, in the starved rat, is limited by the rate of protein turnover. PMID- 3084728 TI - Effect of guar gum, lignin and pectin on proteolytic enzyme levels in the gastrointestinal tract of the rat: a time-based study. AB - The effects of dietary pectin (P), guar gum (G) and lignin (L) on stomach emptying and potential levels of pepsin, trypsin and chymotrypsin during a 2-h period after force-feeding were investigated in growing rats. All of the fibers delayed stomach emptying by 21-26 min. Total potential pepsin activity over 2 h decreased for P (57%), G (44%) and L (20%). In the intestine, total potential trypsin activity over 2 h increased for L (16%) but decreased for P (21%). Total potential chymotrypsin activity over 2 h increased for L (54%) and G (39%). Sixteen to 21% of the variability in intestinal activity over time was statistically attributable to variation in the weight of intestinal contents. The results indicate that fiber components altered proteolytic enzyme levels in the gastrointestinal tract, but the decreased protein utilization previously observed with these fibers is probably not due to reduced levels of intestinal proteases. PMID- 3084730 TI - Dietary potentiation of the antifertility effects of 5-thio-D-glucose in male rats. AB - Male rats of proven fertility were fed the following diets for 28 d either with or without 0.075% 5-thioglucose (5-THG): AIN-76 diet (A76): a diet with 13% casein, 2% glucose and the balance of the calories as free corn oil fatty acids from corn oil (2G); and a similar diet, isocaloric with 2G, with the glucose level increased to 20% (20G). The diets alone without 5-THG had no influence on any of the parameters measured. Body weight gain was lower in rats fed diets containing 5-THG than in those fed diets without 5-THG. In rats fed A76, the only 5-THG effects on male reproductive tract (MRT) tissues was the appearance of testicular multinucleate giant cells (MGC). In rats fed either 2G or 20G, the MRT effects of 5-THG included the appearance of MGC, a lower number of germ cells at most stages of maturation, lower sperm counts and biochemical changes in testis slices and in germ cell preparations compared to rats not fed 5-THG. There were fewer Step 7 spermatids in rats fed 5-THG in 2 G than in those fed 5-THG in 20G. It is concluded that the MRT toxicity of 5-THG is influenced by diet, being potentiated by the low protein diet high in free fatty acids and, to a lesser extent, by low glucose levels within these diets. PMID- 3084729 TI - Total parenteral feeding of rats with an acetoacetate monoglyceride and glucose mixture. AB - Total parenteral nutrition (TPN) by means of monoacetoacetin (glycerol monoacetoacetate) was compared with TPN by using glucose-glycerol. Growth and urinary nitrogen, copper and zinc over 7 d and leucine dynamics on the last day were studied. Complete intravenous diets were administered to five groups of rats which were differentiated by receiving 45 kcal/d (group A) or 65 kcal/d (group C) from a 50% glucose-50% glycerol mixture, 45 kcal/d (group B) or 65 kcal/d (group D) from a 67% monoacetoacetin-33% glucose mixture, or 45 kcal/d (group E) from 100% monoacetoacetin. Leucine kinetics were determined by continuous infusion. Animals from groups A and C were hyperglycemic and normoketonemic, groups B and D were normoglycemic and hyperketonemic, and group E tended to be normoglycemic and hyperketonemic. Group B rats gained weight and retained the most nitrogen while groups A and E lost weight and groups C and D maintained their weight. Nitrogen losses correlated with weight changes. Urinary copper and zinc were not increased by giving ketone bodies. Leucine kinetics were found to be low for group C compared to its energy-matched group, and leucine metabolism was not correlated with nitrogen output and growth. The data suggest that a monoacetoacetin-glucose mixture is preferable as a nonprotein energy source for TPN when compared to either substance alone. PMID- 3084731 TI - Effects of a corporate health promotion program. AB - The effects of a pilot health promotion program at AT&T Communications were evaluated. The study group was given an initial health risk appraisal and offered health education modules. A control group was given the health risk appraisal with no modules; a second control group was neither given the health risk appraisal nor offered modules. The health promotion program was found to lower health risks and improve health-related and job-related attitudes among the study group. Participants in specific intervention modules experienced gains in positive health behaviors. PMID- 3084732 TI - Teratogenic potential of valproic acid. AB - Valproic acid administration in pregnancy may be a potential teratogen to the developing fetus. Numerous animal studies have linked valproic acid to vertebral anomalies and renal agenesis. Recent European data have suggested valproic acid as a causal agent of neural tube defects in human offspring. Research relative to teratogenicity of valproic acid administration for petit mal epilepsy is reviewed. Conclusions indicate that the benefits of valproic acid administration outweigh the hazards of teratogenicity. PMID- 3084733 TI - Life-threatening sublingual hematoma in a severely hemophilic patient with factor VIII inhibitor. AB - The management of a patient with Factor VIII inhibitor in whom a marked hematoma of the sublingual region developed is described. Administration of activated prothrombin complex concentrates and nasotracheal intubation with the fiberoptic laryngoscopy were used in the management of this patient. PMID- 3084734 TI - Comparison of depth and profile of osteotomies performed by rapid superpulsed and continuous-wave CO2 laser beams at high power output. AB - Osteotomies performed by continuous-wave (CW) and rapid superpulsed (RSP) CO2 lasers at high power outputs are compared. Both the RSP and CW modes were able to cut frozen cortical bone at a velocity of 2 mm/second. The RSP laser produced slightly more shallow cuts with profiles that were far superior, especially when lenses with longer focal lengths were employed. The RSP laser seems promising for use in osteotomies because it reduces paraincisional damage. PMID- 3084735 TI - Chemiluminescence in the assessment of polymorphonuclear leukocyte function in chronic inflammatory periodontal disease. AB - Polymorphonuclear neutrophils (PMN's) constitute the primary host resistance factor against infection. They are prominent cells in both the gingival tissue and gingival sulcus in most forms of periodontal disease. Although defective PMN function has been implicated in the pathogenesis of localized juvenile periodontitis (LJP) and rapidly progressive periodontitis (RPP), this may not necessarily be the case in adult periodontitis (AP). A number of studies have failed to detect PMN dysfunction in AP. However, it may be that in this form of chronic inflammatory periodontal disease (CIPD) the defects in peripheral blood PMN function are subtle and the methods used may lack the necessary sensitivity. Chemiluminescence (CL) is the light energy produced by the PMN during its interaction with bacteria or other particles and has been demonstrated to correlate well with antibacterial integrity. Measurement of CL produced by phagocytically challenged PMN's may provide a very sensitive assay of the functional ability of these cells, and, hence, may be useful in assessing PMN activity in CIPD. Recent studies using PMN's obtained from periodontal diseased patients challenged with the periodontopathic organism Fusobacterium nucleatum have revealed an elevated CL response compared to non-diseased controls. These results are reviewed and areas for future research discussed. PMID- 3084736 TI - Kimura's disease and its relation to angiolymphoid hyperplasia with eosinophilia: report of three cases and review of the literature. AB - Kimura's disease, eosinophilic granuloma of soft tissues, is a chronic inflammatory condition and appears as subcutaneous tumor-like nodules in the head and neck regions. Histopathologically, it is characterized by the presence of lymphoid follicles, marked infiltration of eosinophils, fibrosis and vascular proliferation. This disease occurring in the orofacial region is relatively rare, only 14 cases having been previously reported. We describe 3 additional cases of Kimura's disease and discuss these in relation to angiolymphoid hyperplasia with eosinophilia. PMID- 3084737 TI - In vitro growth characteristics of human odontogenic keratocysts and dentigerous cysts. AB - Using an in vitro system, the growth characteristics and enzyme histochemical properties of 3 odontogenic keratocysts and 3 dentigerous cysts were studied. It was found that the epithelial cells of the keratocysts but not of the dentigerous cysts grew in vitro. Furthermore, the epithelial-like cells of the keratocysts showed the same activities of acid phosphatase and NADH-diaphorase in vitro as earlier described in vivo. These enzymatic activities were increased in epithelial-like cells close to proliferating fibroblast-like cells, indicating a close relationship between these two cell types. The results are discussed in the light of the known clinical behaviour of the keratocyst and certain conclusions are also drawn concerning the suggested neoplastic potential of the keratocyst. PMID- 3084738 TI - Histodifferentiation and ultrastructure of oral squamous cell carcinoma in HMT rats. AB - Seven oral squamous cell carcinomas developed in HMT rats were studied with light and electron microscopy. Two carcinomas in extra-oral sites were also described. Histodifferentiation of oral squamous cell carcinomas ranged from well differentiated to poorly-differentiated, comparable to that of the same disease in humans. Ultrastructural features characteristic of human oral carcinomas were observed in the HMT rat carcinomas. PMID- 3084739 TI - Chromosomal breaks and sister chromatid exchanges (SCE) in patients with herpetic stomatitis. AB - Chromosomal breakage and sister-chromatid exchanges (SCE) were studied in peripheral lymphocytes of 9 patients with primary herpetic stomatitis (PHS), 12 patients with secondary herpetic stomatitis (SHS) and 12 controls. The incidence of chromosomal breakage was significantly higher in PHS patients (mean 23%, P. = 0.0002) and in SHS patients (mean 20.25%, P. = 0.0003) compared to the controls (mean 4.2%). The incidence of SCE per 46 chromosomes was significantly higher in SHS patients (mean 16.564) compared with (P. less than 0.001) the controls (mean 11.367) and compared with (P. = 0.006) the PHS patients (mean 12.131). It is concluded that both PHS and SHS patients exhibit structural chromosomal damage; SHS patients in addition exhibit more repaired chromosomal lesions. PMID- 3084740 TI - Ultrastructure of altered rat enamel beneath fluoride-induced cysts. AB - The effect of a single injection of sodium fluoride (60 mg/kg) on the development of rat molar enamel beneath fluoride-induced subameloblastic cysts was studied by transmission electron microscopy using undecalcified sections. Three bands of altered enamel were identified and defined as the cyst surface band, the hypoplastic band, and the hypercalcified band. The irregular cyst surface band, not previously described, was found to have two components: electron-dense enamel globules and organic spherules. The electron-dense globules consisted of small, randomly arranged crystals (confirmed by selected area electron diffraction) occurring within a stippled organic matrix. The organic spherules have staining properties similar to stippled material and lack a crystalline component. They may be a form of organic material being extruded from the underlying developing enamel. The critical role of normal matrix production and ameloblast Tomes' process structure on the development of the crystal orientation and rod pattern is discussed. PMID- 3084741 TI - Malignancy grading in oral squamous cell carcinoma. I. Squamous cell carcinoma of the tongue and floor of mouth: histologic grading in the clinical evaluation. AB - In a retrospective histological and clinical study, a multifactorial grading system was used for histological classification and grading of malignancy in 51 cases of squamous cell carcinoma of the tongue and floor of mouth. The results indicated that the use of such a multifactorial grading system, consisting of 7 morphological parameters, including an evaluation of both the tumor cell population itself and the tumor-host relationship, can serve as an important supplement to clinical judgement in determining the outcome of the oral tumor. PMID- 3084742 TI - Age-related increase of focal lymphocytic infiltration in the human submandibular glands. AB - Histopathological studies were made on the submandibular glands, obtained from 207 autopsy cases of patients, ranging in age from 40-98 years who had not had collagen diseases. Focal lymphocytic infiltration of the submandibular glands was more frequently seen in the cases of patients over 70 years (80.3%) than in those of under 70 years (53.8%). Generally, the incidence of focal lymphocytic infiltration showed a trend to gradual increase with age. Immunohistochemically, a predominance of T cells (60-80%) was found in submandibular lesions with the majority (60-70%) belonging to the Leu 3a+ subset (Helper/Inducer) and with less than 20% belonging to the Leu 2a+ subset (Cytotoxic/Suppressor). The percentage of Leu 2a+ subset was found to increase in the lesion of the periacinar area, and the acinar parenchyma appeared gradually to be damaged by the infiltrating lymphocytes. The findings in the present study suggest that focal lymphocytic infiltration in submandibular glands is a focal sign of immunological disorder, based on the autoimmunity associated with aging. PMID- 3084744 TI - Diagnosis-related group and other prospective payment systems: problems and prospects. PMID- 3084743 TI - [On the N1 latency prolongation in guinea pigs treated with nitrogen mustard-N oxide with special reference to narrow-band analysis]. PMID- 3084745 TI - Nephrotic syndrome and hypertension in two children with Hurler syndrome. PMID- 3084746 TI - Cardiomyopathy and skeletal myopathy in an unusual variant of GM1 gangliosidosis. PMID- 3084747 TI - Lorazepam therapy of status epilepticus in children and adolescents. PMID- 3084748 TI - Lack of validity of diagnosis-related group payment systems in an intensive care population. AB - Case mix based on diagnosis-related groups (DRGs) was studied over 3 years for duration of stay and mean charges for a pediatric intensive care unit (PICU) and a general ward (WARD) population. Case mix variation for 2403 PICU and 14,552 WARD patients was analyzed, and a subset of 856 PICU and 2222 WARD patients examined for variations in duration of stay and mean charges in nine DRGs. Whereas case mix by DRG was consistent over time for both groups, the PICU case mix differed consistently from WARD case mix (P less than 0.001). After adjustment for inflation and for differences in case mix, average stay for the PICU was 10.7 days, versus 6.1 for the WARD (P less than 0.025), with a mean charge of $7172 per PICU and $2946 per WARD patient (P less than 0.01). Furthermore, the case mix-adjusted differences in duration of stay and mean charge between the PICU and WARD populations increased over time. Pediatricians will need to address DRG-based reimbursement systems that place intensive care units, and their institutions, at a significant financial disadvantage. PMID- 3084749 TI - Immunologic aspects of surface infections in the lung. AB - The hallmark of cystic fibrosis is progressive bronchopulmonary damage associated with chronic infection with Pseudomonas aeruginosa, leading to respiratory failure and, ultimately, death. P. aeruginosa is an essentially nonvirulent organism in an immunocompetent host, but it has been shown to colonize the respiratory tract progressively in more than 80% of patients with CF. Patients with CF do not exhibit any evidence of immunologic compromise, and the infection is limited to the mucosal surfaces of the respiratory tract. Thus, P. aeruginosa in bronchopulmonary disease is a unique chronic mucosal infection resulting in a progressive pathologic process. It is therefore conceivable that locally induced alteration in the pulmonary mucosal defense is a major mechanism underlying the development of lung disease in patients with CF. An understanding of immunologic homeostasis in the mucous membranes and in the bronchopulmonary epithelium should provide a better perspective on the factors contributing to the acquisition and chronicity of P. aeruginosa infection in the lower respiratory tract and the development of progressive pulmonary damage unique to CF. PMID- 3084750 TI - The relationship of Phialophora verrucosa to Phialophora americana. AB - Phialophora verrucosa and P. americana, two dematiaceous hyphomycetes, are known to cause chromoblastomycosis. Even though most medical mycologists consider P. americana as synonymous with P. verrucosa, others maintain them as two distinct species on the basis that the phialides of P. americana have deeper collarettes than those of P. verrucosa. Thirty-two isolates, identified either as P. americana or P. verrucosa, were studied for their morphologic, physiologic, and antigenic characteristics to evaluate their taxonomic status. Collarette morphology was found to be a variable character in 12 of the 32 isolates. Those 12 produced phialides with both shallow and deep collarettes. All of the isolates hydrolysed urea within 7 days at 25 degrees C, and failed to liquefy gelatin after 3 weeks at 25 degrees C. None of the isolates decomposed casein, xanthine, or hypoxanthine at the end of 3 weeks at 25 degrees C. All decomposed tyrosine. They grew at 25 degrees C and 37 degrees C, but failed to grow at 40 degrees C. The antigenic relationship between the two species was studied by the exoantigen procedure. The 32 isolates showed close antigenic relatedness. Adsorptions of antisera with homologous and heterologous antigens rendered the antisera free of precipitin bands when studied by the microimmunodiffusion test. The depth of phialide collarettes produced by the two species, being found to be variable character, and the identical nature of the two species with respect to their physiologic and antigenic characteristics, led us to conclude that P. americana should be considered as a synonym of P. verrucosa. PMID- 3084751 TI - Criteria for extracorporeal membrane oxygenation in a population of infants with persistent pulmonary hypertension of the newborn. AB - Extracorporeal membrane oxygenation (ECMO) has been available since 1975 as a therapy of last resort to provide adequate oxygenation for term infants with acute lung disorders that do not respond to maximal medical therapy. Virtually all term infants with serious lung disease have persistent pulmonary hypertension of the newborn (PPHN) characterized by significant right-to-left shunting of blood and severe diffusion defects manifested as increased alveolar-arterial oxygen gradients (AaDO2). Criteria for initiation of ECMO therapy have been developed in several institutions but at the present time there are no universal criteria applicable to all infants with PPHN. We have attempted to establish entry criteria that may be used for different populations of infants with PPHN. Based on a retrospective review of 30 infants with PPHN in our institution, we have defined standards of maximal medical therapy. An alveolar-arterial oxygen difference (AaDO2) of greater than or equal to 610 for 8 hours has been shown to be associated with 79% mortality in this population. This AaDO2/time interval is established as a major criterion for institution of extracorporeal membrane oxygenation. PMID- 3084752 TI - Saphenofemoral venous cutdowns in the premature infant. AB - Thirty-five preterm neonates that had 42 central venous lines placed via saphenofemoral cutdown in the groin are reviewed. The mean gestational age was 29 weeks; mean birth weight 1,320 g. There were no catheter-associated deaths. Minor complications occurred in 50% of patients. Leg swelling (43%), catheter occlusion (12%), and catheter fluid leakage (10%) were the most common. Infections were minor and occurred in 8% of the cases. We believe this study shows the effectiveness and safety of the saphenofemoral cutdown for central venous access in the premature neonate. PMID- 3084753 TI - An easy technique for long-term central venous catheterization and subcutaneous tunneling of the silastic catheter in neonates and infants. AB - Venous access is a common problem in the care of seriously ill infants and neonates on pediatric and pediatric surgical services, and recently there has been a high increase in indications for central venous lines. With the development of many types of silastic catheters, a new safe and fast method of catheter insertion, subcutaneous tunneling and fixation has been developed. Our method is based on Yoffa's (1965)1 description. In the past we used infraclavicular subclavian venipuncture,2 but now we prefer to use the supraclavicular subclavian venipuncture as the first choice in children. Thirty one catheters were placed in 27 consecutive patients ranging in age from two days to ten years. Perioperative complications were nil, and those catheterized for a long period of time had relatively few complications. PMID- 3084754 TI - Comparison of percutaneous and surgical placement of central venous catheters in neonates. AB - A comparison of randomized placement of percutaneous and surgical central venous catheters was made in 53 low birthweight infants. Twenty-eight infants received percutaneous central venous lines, and 21 infants underwent surgical placement of catheters. The incidence of complications did not differ between the groups. The mean length of time the catheter was in place also was similar. Percutaneous placement of central venous catheters appears to compare favorably with the traditional surgical approach. PMID- 3084755 TI - Ultrasound contributions to the management of the severely isoimmunized fetus. AB - Twenty-four out of 81 fetuses affected by anti-D isoimmunization underwent ultrasonic guided intrauterine transfusions (2.8 I. U. T.s per fetus). The absolute value and trend of delta OD 450 micron value was correlated with the severity of fetal condition as evaluated by ultrasonography following simple semiquantitative grading of ascites (mild, moderate, severe) and diagnosis of hydrops. The evaluation of disease was monitored in this way during transfusion therapy. Transfusion procedures have been ultrasonically guided. When ascites was present a few milliliters of isolytic solution allowed the bubbling effect to be observed. In the case of no ascites we confirmed the needle positioning by a cineradiographic sequence lasting a few seconds. Fetal transfusions were repeated every 10 to 15 days and the amount of packed red cells to be injected was determined according to the week of gestation. Post-transfusion monitoring included ultrasonic reevaluation of fetal parameters and non-stress testing. All fetuses were delivered via cesarean section before the 35th week of gestation. In no case was treatment started after the 31st week. Seventeen fetuses were transfused before the 26th week (71%). In 13 fetuses transfusions were started before ascites had appeared. Only 5 fetuses worsened and the 3 which became hydropic eventually died. The delta OD-450 value of these 5 cases before therapy had already indicated that they were more severely affected. Survival rate in this group was 69%. Eleven fetuses showed different degrees of ascites or hydrops at the time of the first transfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084756 TI - Evaluation of enteral feeding pumps for pediatric use. PMID- 3084757 TI - The bioavailability of oral nitroglycerin. AB - In the 1970's, the efficacy of oral nitroglycerin therapy was seriously challenged, primarily on the basis of animal studies showing complete first-pass hepatic metabolism of nitroglycerin. Today, it is generally accepted that high oral doses of nitroglycerin do show antianginal efficacy. It has been suggested that this efficacy results from saturation of hepatic metabolism by the large oral doses administered, although the experimental evidence in humans purporting to support this may be questioned. In the present investigation, the bioavailability of oral nitroglycerin when administered in a capsule dosage form and as a solution was determined. Oral doses of nitroglycerin were less than 1% bioavailable. However, substantially high concentrations of the relatively low activity dinitrate metabolites were measured in plasma. We hypothesize that the activity of oral nitroglycerin preparations may result from high concentrations of the dinitrate metabolites, although this was not directly tested in the bioavailability studies described here. PMID- 3084758 TI - Relative bioavailability of two spray formulations of nitroglycerin. AB - Twelve healthy male volunteers received two sublingual doses of 0.4-mg nitroglycerin from two metered-dose spray products, A and B. Plasma samples were collected immediately before and for up to 6 h following each dose. The samples were immediately extracted and analyzed for nitroglycerin. The results show striking differences between the two formulations. The mean AUC for preparation A, 159 +/- 66 h X pg/mL, was 2.7 times greater than for B, 59 +/- 33 h X pg/mL. The mean maximum plasma concentration for A was 1387 +/- 620 pg/mL which was 4.1 times greater than the mean maximum plasma concentration for preparation B (340 +/- 234 pg/mL). The time of maximum plasma concentration also occurred earlier for preparation A versus B, 4.3 +/- 1.6 versus 8.3 +/- 2.0 min, respectively. Such bioavailability differences may indicate therapeutic advantages for preparation A. PMID- 3084759 TI - Prostaglandins participate in the renal vasodilation due to hydralazine in dogs. AB - The authors studied the effects of bolus injections of hydralazine (500 micrograms) into the renal artery of chloralose-anesthetized dogs. In control dogs, hydralazine injection resulted in an increase in renal artery blood flow of 110 +/- 10.4 ml/min (53 +/- 4.7%) from 214 +/- 28 ml/min. In dogs that were pretreated with the alpha-1 adrenergic antagonist, prazosin (1 mg/kg), hydralazine injection increased renal blood flow by 95 +/- 22 ml/min (37 +/- 7.4%) from 253 +/- 19 ml/min, an increase not different from that found in control dogs. However, in dogs pretreated with indomethacin (5 mg/kg) or sodium meclofenamate (3 mg/kg), inhibitors of cyclooxygenase, hydralazine injection resulted in an increase in renal artery blood flow of only 44 +/- 5.3 ml/min (19 +/- 2.7%) from 235 +/- 23 ml/min, an increase significantly different from that in control dogs (P less than .05). The renal blood flow response to hydralazine injection developed slowly, reached a maximum in 20 min and was maintained for at least 1 hr. Arterial blood pressure, heart rate and descending aortic blood flow were not significantly changed after hydralazine injection. The authors conclude that hydralazine increases renal blood flow in dogs by a mechanism independent of alpha-1 adrenergic receptors and that this increase is, in large part, mediated by prostaglandin release. PMID- 3084760 TI - Effects of prostaglandin synthesis inhibition on sympathetic-and parasympathetic mediated coronary hemodynamic responses. AB - In chloralose-anesthetized dogs with the left circumflex coronary artery perfused at constant flow, the effects of indomethacin or naproxen on coronary and systemic responses to sympathetic and parasympathetic stimulation were evaluated. Sympathetic stimulation was evoked either by 1-min carotid artery occlusion or by epinephrine (5 micrograms) or norepinephrine (5 micrograms) intracoronary administration. Reflex or direct parasympathetic stimulation was produced by ouabain (40 micrograms) or acetylcholine (2.5 micrograms) injection, respectively, in the perfused coronary artery. The administration of indomethacin or naproxen reduced the integrated areas of coronary vasodilatation induced by epinephrine and norepinephrine. The extent of this reduction was dose-dependent with both indomethacin (epinephrine: r = 0.774, n = 35, P less than .001; norepinephrine: r = 0.766, n = 35, P less than .001; norepinephrine: r = 0.799, n = 35, P less than .001) up to 1.5 and 7 mg/kg, respectively. Further increase in dosage of both prostaglandin synthesis inhibitors failed to induce further reduction of integrated areas of coronary vasodilatation. In contrast, the maximum fall in coronary perfusion pressure, induced by both catecholamines, remained unmodified after inhibition of prostaglandin synthesis, whereas a faster return of the perfusion pressure to base line was observed. The extent of cyclooxygenase activity inhibition induced by indomethacin or naproxen, assessed through the radioimmunoassay of thromboxane B2, showed a consistent dose dependent increase until complete inhibition was attained with 1.5 mg/kg of indomethacin and 7 mg/kg of naproxen. No significant change in the coronary and systemic hemodynamic response induced by carotid occlusion and by ouabain or acetylcholine intracoronary administration was observed. Furthermore, complete cyclooxygenase inhibition, induced by either indomethacin or naproxen, was able to reduce the coronary vasodilatation induced by isoproterenol (5 micrograms) intracoronary injection but failed to modify the coronary vasoconstriction elicited by both epinephrine and norepinephrine in propranolol-treated dogs. These data indicate that the prostaglandin system is involved in the coronary vasodilatation induced by humoral sympathetic stimulation, whereas coronary hemodynamic responses to both neural sympathetic or parasympathetic stimulation are not influenced by the administration of prostaglandin synthesis inhibitors. PMID- 3084761 TI - Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta. AB - This study was conducted to test the hypothesis that biotransformation of glyceryl trinitrate (GTN) is involved in GTN-induced relaxation of vascular smooth muscle. Isolated rabbit aortic strips (RAS) were contracted submaximally with phenylephrine (PE) and then were incubated with 0.5 microM [14C]GTN in a time course study. GTN-induced relaxation (inhibition of PE-induced tone) of RAS was monitored and tissue GTN and glyceryl-1,2- and 1,3-dinitrate (GDN) concentrations were measured by thin-layer chromatography and liquid scintillation spectrometry at 0.5, 1, 2 and 20 min after incubation. Biotransformation of GTN to GDN occurred during GTN-induced relaxation of RAS. The tissue GDN concentration was dependent on the time duration of incubation with GTN and was related to the magnitude of GTN-induced tissue relaxation. At the 20-min interval, the GDN concentration in the incubation medium indicated appreciable efflux of GDN metabolites from the RAS. In the biotransformation of GTN by RAS, there was about 4-fold preferential formation of 1,2-GDN compared with 1,3-GDN. RAS were made tolerant to GTN in vitro by incubation with 500 microM GTN for 1 hr. After washing, GTN-tolerant and nontolerant (incubation with vehicle for 1 hr) RAS were contracted submaximally with PE, and then were incubated with 0.5 microM [14C]GTN for 2 min. GTN-induced relaxation of RAS and tissue GDN concentration were significantly less for GTN-tolerant tissue compared with nontolerant tissue. Tissue GTN concentration was similar for both GTN tolerant and nontolerant RAS, which indicated that the tissue uptake of GTN was similar and that GTN biotransformation was diminished in tolerant tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084762 TI - Furosemide pharmacodynamics: effect of respiratory and acid-base disturbances. AB - The aims of this study were to investigate the effect of changes in arterial blood gases and pH on furosemide pharmacodynamics and kinetics. Five groups of conscious rabbits were used: a control group breathing air with normoxia and normocarbia; a second group with hypercapnia and respiratory acidosis; a third with hypoxemia; a fourth with hypercapnia and respiratory acidosis combined with hypoxemia (HCHO); and the fifth group with metabolic acidosis. All experimental conditions, except hypoxemia, increased sodium tubular reabsorption and therefore, decreased urinary excretion of sodium. Renal blood flow was decreased by HCHO and metabolic acidosis. In response to 5 mg/kv i.v. of furosemide, natriuresis and diuresis were decreased by an average of 44% in animals with HCHO (P less than .05). The kinetics of furosemide were not affected by any of the experimental conditions except HCHO, in which the renal clearance of furosemide was reduced from 7.5 +/- 1.4 ml/min/kg (controls) to 2.7 +/- 0.7 ml/min/kg (P less than .05). The reduction in renal clearance of furosemide was associated with a decrease in urinary excretion of sodium (P less than .05). The reduction in renal clearance of furosemide was probably secondary to the decrease in renal blood flow and an increase in furosemide tubular reabsorption. Finally, HCHO did not decrease plasma volume, suggesting that the reduction in renal blood flow was secondary to blood flow distribution. In conclusion, only hypercapnia and respiratory acidosis combined with hypoxemia decreases the natriuretic and diuretic effect of furosemide. PMID- 3084763 TI - Requirement for reduced, unliganded hemoprotein for the hemoglobin- and myoglobin mediated biotransformation of glyceryl trinitrate. AB - The biotransformation of glyceryl trinitrate (GTN) by hemoglobin (Hb) and myoglobin (Mb) was assessed using solutions of various forms of the hemoproteins, viz., the oxy-, deoxy-, carbonmonoxy- and met-forms. After incubation with these, GTN loss was observed only with the deoxy-forms of Hb and Mb. The stoichiometry and products of [14C]GTN biotransformation by deoxy-Hb and deoxy-Mb were determined by measuring the formation of [14C]glyceryl dinitrate [14C]GDN), met Hb (or met-Mb) and inorganic nitrite anion. Biotransformation of GTN involved the oxidation of 2 mol of heme iron (II) per mol of GTN biotransformed to GDN and inorganic nitrite anion. In addition to the formation of GDN, 1 to 2.5% of the radioactivity could not be extracted from the incubation samples. The ratio of 1,2-GDN/1,3-GDN formed during incubation of deoxy-Hb with GTN was 11:1, which indicated a high degree of regioselectivity for the denitration of the nitrate ester group in position 1 or position 3 of GTN. The metabolite ratio obtained for deoxy-Mb incubation with GTN (1,2-GDN/1,3-GDN,3:1) was less than that for deoxy Hb, which indicated less regioselectivity for the deoxy-Mb-mediated denitration reaction. This could reflect differences in the topography of the heme pocket of the two hemoproteins and steric differences in the GTN-hemoprotein interaction. PMID- 3084764 TI - Effects of thioglucoses on sensitivity to insulin hypoglycemic convulsions. AB - Based on the effects of gold thioglucose (GTG), we have previously proposed a regulatory center in brain which adjusts the convulsive response to insulin hypoglycemia. The sensitivity to insulin hypoglycemic convulsions is decreased 24 hr and increased 1 week after a single i.p. injection of GTG. The differences are in the brain's convulsive response to equal hypoglycemia, as the blood glucose response to insulin is unchanged. The generalized convulsive threshold, reflected in the sensitivity to nonmetabolic pentylenetetrazol (Metrazol) convulsions, is not altered. Despite its systemic administration, GTG causes lesions focused in the ventromedial hypothalamus. In the present study, this regulatory center was explored further by the ability of two thioglucoses to substitute for GTG. beta-D Thioglucose had no effect. 5-Thioglucose simulated the early (24 hr) action of GTG but had no effect at 1 week. However, unlike GTG, 5-thioglucose did not cause the ventromedial hypothalamus lesion. The early (24 hr) and late (1 week) components are thus dissociated. The early effect on insulin hypoglycemic convulsions does not require a ventromedial hypothalamus lesion. Structure activity relationships and relationships to glucoregulatory systems are discussed. PMID- 3084765 TI - Extracellular calcium-dependent and -independent effects of methylmercury on spontaneous and potassium-evoked release of acetylcholine at the neuromuscular junction. AB - Acute bath administration of methylmercury (MeHg) to the murine neuromuscular junction causes an initial surge in the frequency of occurrence of miniature end plate potentials (MEPPs), followed by a complete suppression of asynchronous spontaneous release. The goals of the present study were to determine: whether the MeHg-induced in MEPP frequency was dependent upon extracellular Ca++, whether MeHg produced this effect by actions within the motor nerve terminal and whether the secondary suppression of release was due to transmitter depletion. Conventional intracellular microelectrode recording measurements of MEPPs were made from myofibers of the isolated hemidiaphragm of the rat. Increasing the bath concentration of Ca++ from 1 to 2 or 4 mM decreased the time period required by 100 microM MeHg to produce a peak increase of spontaneous release from 52 to 39 to 28 min, respectively. Further increasing bath Ca++ to 8 mM actually increased this period back to 49 min. Increasing [Ca++]o had no consistent effect on the magnitude of the MeHg-induced increase in MEPP frequency. After depolarization of the nerve terminal with elevated extracellular K+ (15 mM) the time to peak increases in MEPP frequency was shortened from approximately 40 min to 1 to 2 min. The time required for MeHg to cause complete cessation of MEPPs was also shortened. In experiments conducted in K+-depolarized preparations to which no Ca++ was added, MeHg still increased MEPP frequency, although not as rapidly, or to the same extent as in solutions containing Ca++.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084766 TI - The role of hyperpolarization in the relaxation of smooth muscle of monkey coronary artery. AB - In monkey coronary arteries, outer and inner muscle had a similar resting potential (-39.5 and -40.0 mV). Both showed strong outward-going rectification, with no regenerative depolarization, on injection of depolarizing current. The depolarization spread electrotonically in all directions, particularly around the vessel wall. Hyperpolarization up to -45 mV by injection of constant current caused relaxation. Depolarization caused contraction. Pulses of field stimulation caused a brief depolarization which was reduced by tetrodotoxin or by stripping of the adventitia. They also caused a prolonged hyperpolarization which was not prevented by either, but was prevented by rubbing of the endothelium. The hyperpolarization in response to field stimulation therefore appears to result from electrically stimulated release of a substance from endothelial cells. Relaxation accompanied this hyperpolarization. It was twice the size of the relaxation produced by a similar hyperpolarization due to constant injection. Isoprenaline also produced hyperpolarization, and relaxation five times that seen with a similar hyperpolarization induced by direct current. Hyperpolarization appears to be an important, but not the only, mediator of relaxation induced in this artery both by endothelial cells and by beta-adrenergic stimulation. PMID- 3084767 TI - Gonadal development and gonadotrophin secretion in the male vole (Microtus agrestis) after an abrupt change in photoperiod. AB - Male voles were reared from birth to age 28 days in 6L:18D. Pairs of animals showing similar sexual development were assigned at random to 16L:8D or 6L:18D. Treatments continued for a further 56 days. Increase in the activity of the hypothalamo-hypophysial system occurred within 4 days of exposure to 16L:8D, as shown by significant elevation of plasma LH and FSH. Pituitary LH did not increase until Day 7, and pituitary FSH did not increase until Day 21. After exposure to 16L:8D for 4 days, pituitary FSH was lower than in corresponding animals in 6L:18D. These discrepancies between pituitary and plasma values of gonadotrophins indicate that increase in hormone release occurs before synthesis is fully stimulated. Enhanced output of testicular hormones probably began between Day 7 and Day 14, as indicated by an increase in seminal vesicle weight, yet plasma and pituitary concentrations of LH and FSH remained elevated. This suggests that long photoperiods may cause direct stimulation of the hypothalamo hypophysial system which increasing values of testicular hormones are initially unable to inhibit. The response of this system in voles to an abrupt change from a non-stimulating to a stimulating photoperiod has a time course resembling that for the Soay ram but appreciably slower than for the Japanese quail. PMID- 3084768 TI - Ornithine decarboxylase inhibition and the uterotrophic response to oestrogen in rats. AB - Pretreatment of mature ovariectomized rats with DL-5 alpha difluoromethylornithine (DFMO) inhibits the 6-h uterine blood flow response to oestradiol and also depresses the stimulatory effect of oestradiol on wet and dry uterine weight. Results from this study indicate that polyamine synthesis is implicated in the uterine response to oestrogen. PMID- 3084769 TI - Plasma concentrations of gonadotrophins, preovulatory follicular development and luteal function associated with bovine follicular fluid-induced delay of oestrus in heifers. AB - In Exp. 1, injections of 10 ml bovine follicular fluid (bFF, i.v. or s.c.), given twice daily for 3 days after injection of a luteolytic dose of PGF-2 alpha, delayed the onset of oestrus in 3 of 6 heifers to 8 or 9 days after PGF-2 alpha, as compared with 2 or 3 days after PGF-2 alpha in control heifers. Mean plasma concentrations of FSH and LH during the injection period were not different from those in saline-injected heifers. In Exp. 2, i.v. injections of 20 ml bFF twice daily for 3 days uniformly delayed oestrus to 8 days after PGF-2 alpha (N = 4) and injections of 20 ml bFF i.v. every 6 h for 24h on the day of PGF-2 alpha injection delayed oestrus to 5.0 +/- 0.6 days after PGF-2 alpha as compared with 2.8 +/- 0.3 days for control heifers. In both treatment groups, plasma concentrations of FSH were suppressed during the injection period and increased transiently after treatment, but plasma concentrations of LH during the injection period were not different from those of control heifers. Plasma levels of oestradiol in heifers given bFF remained basal for 2 or 3 days after treatment, then increased several days before the delayed oestrus, in a manner similar to that in control heifers, and elicited normal preovulatory surges of LH and FSH. Plasma concentrations of progesterone and the length of the next oestrous cycle were normal, indicating formation of functional corpora lutea. Therefore, bFF treatments appear to delay oestrus by selectively suppressing plasma FSH, without affecting LH, and delaying the development of the preovulatory follicle. These results suggest that FSH may be critical to support the growth and development of the preovulatory follicle after luteolysis in cows. PMID- 3084771 TI - Ultrastructural features of preovulatory oocyte maturation in superovulated cattle. AB - Cows and heifers were induced to superovulate by treatment with PMSG or FSH. The ultrastructural features of the oocytes were related to the time of the LH peak and the progesterone/oestradiol-17 beta ratios in the follicular fluid. At 0-2 h after the LH peak the perivitelline space developed; at 9-12 h there was disconnection of the junctions between cumulus cell projections and oolemma, and the concomitant breakdown of the oocyte nucleus; at approximately 15 h there were spatial rearrangements in the ooplasm of (a) mitochondrial clusters from a peripheral to an even distribution and (b) vesicles from an even distribution to a more central location; at approximately 19 h there was abstriction of the first polar body with dislocation of mitochondrial clusters and vesicles towards the site of polar body formation; at 21-22 h there was migration of cortical granules to solitary positions along the oolemma and decrease in the sizes of Golgi complexes and, on some occasions, the smooth endoplasmic reticulum. These ultrastructural changes were accompanied by an increase in progesterone/oestradiol ratios in the follicular fluids. It is concluded that preovulatory oocyte maturation in gonadotrophin-stimulated cattle comprises nuclear as well as cytoplasmic changes accompanied by steroidogenic changes in the follicle, each of which are closely related to the time of the LH peak. However, some variation existed between animals, between follicular and oocyte maturation and even within oocytes between nuclear and cytoplasmic maturation. PMID- 3084772 TI - Gonadotrophic control of steroidogenesis in human granulosa-lutein cells. AB - Granulosa-lutein cells were harvested from periovulatory follicles in human ovaries and cultured for up to 6 days, equivalent to almost half of a normal luteal phase. The average rate of basal progesterone accumulation in the culture medium was constant at approximately 36 nmol progesterone/10(6) cells/day. Oestradiol accumulation was too low to measure in the absence of precursor androgen. Basal aromatase activity (measured as oestradiol formed in 3 h from 10( 6) M exogenous testosterone) was high (average 1.15 nmol oestradiol/10(6) cells/3 h) at the time of cell isolation (Day 0) but fell by greater than 90% on Day 1. By Day 2 the activity had partly recovered and averaged 62% of the Day 0 value, rising to 70% on Day 6. This loss and recovery of aromatase activity was independent of the addition of gonadotrophic hormones to the culture medium. However, dose-related increases in aromatase activity occurred in the presence of highly pure human pituitary LH (0.1-30 ng/ml). The increase was observed on Day 4 and was maximal on Day 6 (average 3-fold increase over control) in the presence of LH concentrations greater than or equal to 1.0 ng/ml. LH also caused dose related increases in progesterone accumulation by Day 4 with maximal stimulation on Day 6 (average 3-fold increase over control) at greater than or equal to 10.0 ng/ml. Dose-related stimulation of aromatase activity by human pituitary FSH also occurred but maximal stimulation required the presence of 300 ng FSH/ml and progesterone accumulation was hardly affected at this dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084770 TI - Use of bovine follicular fluid to increase ovulation rate or prevent ovulation in sheep. AB - Romney ewes were injected intramuscularly once or twice daily for 3 days with 0, 0.1, 0.5, 1 or 5 ml of bovine follicular fluid (bFF) treated with dextran-coated charcoal, starting immediately after injection of cloprostenol to initiate luteolysis on Day 10 of the oestrous cycle. There was a dose-related suppression of plasma concentrations of FSH, but not LH, during the treatment period. On stopping the bFF treatment, plasma FSH concentrations 'rebounded' to levels up to 3-fold higher than pretreatment values. The mean time to the onset of oestrus was also increased in a dose-related manner by up to 11 days. The mean ovulation rates of ewes receiving 1.0 ml bFF twice daily (1.9 +/- 0.2 ovulations/ewe, mean +/- s.e.m. for N = 34) or 5.0 ml once daily (2.0 +/- 0.2 ovulations/ewe, N = 25) were significantly higher than that of control ewes (1.4 +/- 0.1 ovulations/ewe, N = 35). Comparison of the ovaries of ewes treated with bFF for 24 or 48 h with the ovaries of control ewes revealed no differences in the number or size distribution of antral follicles. However, the large follicles (greater than or equal to 5 mm diam.) of bFF-treated ewes had lower concentrations of oestradiol 17 beta in follicular fluid, contained fewer granulosa cells and the granulosa cells had a reduced capacity to aromatize testosterone to oestradiol-17 beta and produce cyclic AMP when challenged with FSH or LH. No significant effects of bFF treatment were observed in small (1-2.5 mm diam.) or medium (3-4.5 mm diam.) sized follicles. Ewes receiving 5 ml bFF once daily for 27 days, from the onset of luteolysis, were rendered infertile during this treatment period. Oestrus was not observed and ovulation did not occur. Median concentrations of plasma FSH fell to 20% of pretreatment values within 2 days. Thereafter they gradually rose over the next 8 days to reach 60% of pretreatment values where they remained for the rest of the 27-day treatment period. Median concentrations of plasma LH increased during the treatment period to levels up to 6-fold higher than pretreatment values. When bFF treatment was stopped, plasma concentrations of FSH and LH quickly returned to control levels, and oestrus was observed within 2 weeks. The ewes were mated at this first oestrus and each subsequently delivered a single lamb. PMID- 3084773 TI - Measurement of metabolic turnover in single mouse embryos. AB - The method for estimation of metabolic turnover by a single embryo at each stage of preimplantation development is based on the incubation of an embryo in the presence of labelled substrate at high specific activity in a miniaturized incubation chamber and the subsequent radioassay of metabolic products. Preliminary tests indicated that the treatment did not affect embryos adversely. Estimates of glycolysis, substrate oxidation and incorporation by mouse embryos throughout the whole of the preimplantation period of development were made. This technique could prove particularly useful for investigating substrate requirements and metabolic turnover in species for which few embryos are available for study. PMID- 3084774 TI - Tuberculosis of peripheral joints: an often missed diagnosis. AB - Eleven elderly patients with tuberculous arthritis of 12 peripheral joints were studied retrospectively. The disease usually presented as a monoarticular arthritis often in the absence of other signs of tuberculosis. A delay in diagnosis was a common feature and synovial biopsies provided the highest diagnostic yield. PMID- 3084775 TI - Rheumatoid rigor: gold induced myokymia. A report and review of the literature. AB - Myokymia is a spontaneous movement disorder characterized by slow, undulating, persistent movement of the involved muscles. It is an unusual manifestation of gold neurotoxicity, rarely reported in the rheumatologic literature. We report a case of gold induced myokymia associated with gold-induced dermatitis and nephropathy. PMID- 3084776 TI - Ossification of the plantar fascia and peroneus longus tendons in diffuse idiopathic skeletal hyperostosis (DISH). AB - Extraspinal skeletal changes in diffuse idiopathic skeletal hyperostosis (DISH) consist of bony proliferation at ligamentous and tendinous insertions. We describe a patient with DISH who manifested ossific changes in the plantar fascia and peroneus longus tendon bilaterally at sites not immediately adjacent to the bony insertions of these structures. This observation expands the roentgenographic spectrum of DISH. PMID- 3084777 TI - Hypogammaglobulinemia associated with gold therapy in a patient with juvenile rheumatoid arthritis. PMID- 3084778 TI - Stroke-like syndrome after gold sodium thiomalate induced vasomotor reaction. PMID- 3084779 TI - Widespread gastric ulceration during auranofin therapy. PMID- 3084780 TI - Differential effects of in vitro gold sodium thiomalate on the stimulation of human peripheral blood mononuclear cells by Mycoplasma arthritidis T cell mitogen, concanavalin A and phytohemagglutinin. AB - The effects of in vitro gold sodium thiomalate (GSTM) on peripheral blood mononuclear cells (PBM) stimulated by a Mycoplasma arthritidis T cell mitogen (MAM), concanavalin A (Con A), and phytohemagglutinin (PHA) were compared in 5 individuals by measuring 3H-thymidine uptake by PBM. The MAM induced lymphocyte transformations were more significantly inhibited by in vitro GSTM than parallel assays using Con A and PHA. The effects could not be explained by differences in cell viability, length of cell culture, mitogen concentration, and level of mitogen stimulation, suggesting that MAM may be a useful probe in evaluating the effects of GSTM on immune function. PMID- 3084781 TI - Chrysiasis: the role of sun exposure in dermal hyperpigmentation secondary to gold therapy. AB - To investigate the role of sun exposure in the pathophysiology of chrysiasis, we studied 10 Caucasian female patients with rheumatoid arthritis: 4 with clinically apparent chrysiasis and 6 without apparent pigmentation. Three patients without chrysiasis had received over 4 g of gold and 3 less than one g. The mean melanin score, determined by histological examination of sun exposed and nonsun exposed skin, was significantly higher in the sun exposed skin of the chrysiasis and high dose controls than low dose controls (p less than .05). Concentration of gold measured semiquantitatively by transmission electron microscopy and quantitatively by atomic absorption showed increased gold concentration in sun exposed when compared to nonsun exposed skin of chrysiasis and high dose controls (p = .26). Low dose controls had no gold demonstrated by either method. Our results suggest that gold deposition in the dermis stimulates melain production and that melanin is important in hyperpigmentation of chrysiasis. Furthermore ultraviolet light may induce preferential uptake of gold by the skin. PMID- 3084782 TI - Toxicity due to remission inducing drugs in rheumatoid arthritis. Association with HLA-B35 and Cw4 antigens. AB - Twenty-five patients with rheumatoid arthritis (RA) who developed toxicity while taking remission inducing drugs and 30 without toxicity were studied for possible associations with class I and II HLA antigens. A strong association has been found between nephritis and dermatitis due to Tiopronin (a D-Penicillamine like compound) and class I antigens B35-Cw4, and between dermatitis due to gold thiosulphate and B35. Compared to healthy controls a lower DR5 frequency was observed in patients with RA except for the Tiopronin related nephritis group. PMID- 3084783 TI - Design and synthesis of 2-(arylamino)-4(3H)-quinazolinones as novel inhibitors of rat lens aldose reductase. AB - A number of 2-(arylamino)-4(3H)-quinazolinones (2a-i) that possess several of the pharmacophore moieties necessary for binding to the inhibitor site of the enzyme aldose reductase were synthesized and tested for their ability to inhibit crude aldose reductase obtained from rat lens. Only those quinazolinones that possess an acidic moiety on the 2-(arylamino) substituent were found to display significant inhibitory activity. Of these, the most potent compound is the 4' CO2H derivative (2i) with an IC50 of 34 microM, while the least potent is the 4' OH derivative (2c) with an IC50 of 75 microM. All of the 2-(arylamino)-4(3H) quinazolinones tested are less potent than other known inhibitors of aldose reductase, such as alrestatin and sorbinil, indicating that the pharmacophore moieties present in these compounds may not be positioned optimally relative to one another for maximal interaction with the enzyme. PMID- 3084784 TI - Drug design via pharmacophore identification. Dopaminergic activity of 3H benz[e]indol-8-amines and their mode of interaction with the dopamine receptor. AB - The design and synthesis of a series of 3H-benz[e]indol-8-amines are described. Two of the compounds are potent, orally active dopaminergic agents as established by their ability to induce contralateral turning in rats with unilateral 6 hydroxydopamine-induced lesions of the nigrostriatal pathway, to induce ambulation in rats rendered akinetic by bilateral injections of 6-hydroxydopamine into the anterolateral hypothalamus, and to antagonize reserpine-induced catalepsy in mice. The dopamine agonist activity of the 3H-benz[e]indol-8-amines establishes that a pyrrolo ring and a phenolic hydroxyl group can interact similarly with the dopamine receptor and provides evidence for the existence of a hydrogen-bond acceptor nucleus on the dopamine receptor macromolecule that is involved in the behavioral manifestations of dopamine agonists. PMID- 3084785 TI - Inhibitors of Bacillus subtilis DNA polymerase III. Influence of modifications in the pyrimidine ring of anilino- and (benzylamino)pyrimidines. AB - Substituent effects governing inhibition of DNA polymerase III from Bacillus subtilis were examined in several series of N6-substituted 6-aminopyrimidines. The presence of alkyl groups as large as n-butyl in the 3-position of 6-(5 indanylamino)uracil had no effect on inhibitor-enzyme binding. Substituents in the 4-position of a series of 2-amino-6-(benzylamino)pyrimidines had complex effects: alkoxy and phenoxy derivatives were less active than the parent 4-oxo (isocytosine) compound, but alkylphenoxy and halophenoxy derivatives were more active than the 4-phenoxy compound itself, suggesting that hydrophobic binding can occur between 4-substitutents and the enzyme surface and that space between the pyrimidine ring and pol III may represent the active site of the enzyme. Replacement of 5-H by methyl and ethyl groups drastically decreased inhibitory activity of 6-(benzylamino)- and 6-p-toluidinouracils, but 5-bromo and 5-iodo analogues were equipotent with the parent compounds. These results indicate that the phenyl rings of these compounds must exist in conformations in which they are perpendicular to the pyrimidine ring plane and that charge-transfer stabilization of such "active conformations" may compensate for steric barriers from 5-halo groups in the inhibitor-enzyme complex. PMID- 3084786 TI - A lymphotropic prodrug of L-dopa: synthesis, pharmacological properties, and pharmacokinetic behavior of 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4 dihydroxyphenyl)prop anoyl] propane-1,2,3-triol. AB - A glyceride derivative of L-Dopa, 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4 dihydroxyphenyl)propan oyl] propane-1,2,3-triol (1), was synthesized and tested as an orally administrable prodrug endowed with lymphotropic properties. In the oxotremorine and reserpine tests, 1 exhibited an anti-Parkinsonian activity of longer duration than L-Dopa. The time course of concentration of 1 in the intestinal lymph of rat was determined and compared to that of L-Dopa. The results clearly demonstrate that 1 is selectively absorbed from the intestinal tract by the lymphatic route without any chemical or enzymatic degradation. In the blood of rats and mice, 1 functions as a prodrug to release L-Dopa by hydrolysis. In comparison with L-Dopa itself, higher L-Dopa levels for a longer period of time were observed as well as much more favorable L-Dopa/dopamine ratios. Ultimately, studies using mice show that the administration of 1 brings about a prolonged increase of L-Dopa and dopamine levels in the brain, without initial transient peak in concentration observed after an equimolecular dose of L Dopa. PMID- 3084787 TI - Synthesis and biological evaluation of cyclic analogues of 1-carnitine as potential agents in the treatment of myocardial ischemia. AB - A series of cyclic rigid analogues of l-carnitine has been synthesized and examined for activity as substrates for the carnitine-acylcarnitine translocase, the enzyme that mediates transport of fatty acids into the mitochondria. Synthetic steps to seven of these analogues are described in this paper. Bioassay of these compounds is conducted in a preparation of isolated heart mitochondria that have been previously loaded with [14C]-l-carnitine. Efflux of radioactivity from the mitochondria is then monitored in the presence of the compound being evaluated in order to assess the amount of enzyme activity initiated. The palmityl ester of l-N,N-dimethyl-trans-2-carboxy-4-hydroxypyrrolidinium chloride elicited a 13.63 and 63.07% efflux of [14C]-l-carnitine at concentrations of 3 and 50 mM, respectively. This represents the first instance in which a nonnaturally occurring analogue of l-carnitine has been shown to undergo transport via this mitochondrial translocase, suggesting the possibility that cyclic carnitine analogues may find utility as agents in the treatment of myocardial ischemia. PMID- 3084788 TI - Performance of the Nutromat Pfrimmer enteral feeding system. PMID- 3084790 TI - Cross-reactions in cell-mediated immunity to Salmonella causing enteric fever. AB - Cross-reactivity in a delayed-type hypersensitivity (DH) response was studied in mice immunised with live Salmonella typhi, S. paratyphi A and S. paratyphi B. Extensive cross-reactions outside the serogroup limits were observed. The ability of DH cross-reacting and non-cross-reacting sonicates to generate activated macrophages was studied in mice immunised 3 months earlier with S. paratyphi B. Whereas DH cross-reacting S. poona sonicate generated activated macrophages the non-cross-reacting S. typhi sonicate did not. To determine whether infections due to diarrhoea-causing salmonellae generated cross-reactive cell-mediated immune responses against enteric fever-causing organisms, similar reverse experiments were performed in mice immunised with S. enteritidis. S. paratyphi A sonicate generated both effector responses, i.e., DH and activated macrophages. PMID- 3084789 TI - Chemical composition of the extracellular slime glycolipoprotein of Pseudomonas aeruginosa and its relation to gentamicin resistance. AB - The slime glycolipoproteins (GLPs) extracted from Pseudomonas aeruginosa strain C2 and its laboratory-induced gentamicin-resistant variant were analysed for gross chemical composition. The GLP of the wild-type strain contained significantly greater amounts of neutral sugars, uronic acid and thiobarbituric reactive material (p less than 0.001) than the GLP of the gentamicin-resistant variant. Also significantly higher (p less than 0.01) was the amino-sugar content of the GLP from the wild-type strain. Paper chromatographic analyses of the hydrolysates of the GLPs revealed that two neutral sugars, rhamnose and mannose, were absent from the GLP of the resistant variant. The GLP of strain C2 contained significantly less protein than the GLP of the gentamicin-resistant variant. PMID- 3084791 TI - Phenotypic changes in mycobacteria grown in oxygen-limited conditions. AB - Laboratory strains of Mycobacterium phlei, M. smegmatis, M. fortuitum, M. gordonae, M. kansasi, M. bovis, M. tuberculosis and M. intracellulare were adapted to grow in an anaerobic environment. Concomitant with the transition to anaerobic growth was loss of acid-fastness, loss or modification of colonial pigmentation, and loss of ability to grow on a malachite green-containing medium. The mycobacteria grown anaerobically produced acid from a greater range of carbohydrates than aerobically grown cultures, lost iron-uptake activity, and showed a reduction of urease, catalase and nitratase activity. Back adaption of mycobacteria from an anaerobic to an aerobic environment resulted in the acquisition of acid-fastness, pigmentation, and other characteristics used in the taxonomy of mycobacteria. These results suggest that mycobacterial cultures, if grown in an anaerobic environment, may be erroneously identified in clinical laboratories. PMID- 3084792 TI - Detection of antibodies to Mycobacterium tuberculosis plasma membrane antigen by enzyme-linked immunosorbent assay. AB - Antibody activity against Mycobacterium tuberculosis of sera from an area with a high prevalence of tuberculosis was measured by enzyme-linked immunosorbent assay (ELISA) with a plasma-membrane extract from M. tuberculosis strain H37RV. All sera from relapsed tuberculosis patients and 82.5% of sera from new untreated cases gave positive results. The seronegative group of tuberculosis patients gave positive results by direct microscopy and culture. No clear correlation between antibody and delayed hypersensitivity or extent of disease was observed. Chemotherapy was associated with a higher antibody response. Specificity of the test with healthy control subjects from the high prevalence area was 85%. Negative results were obtained with 145 sera from presumed healthy European subjects and with seven sera from BCG-vaccinated subjects. PMID- 3084793 TI - Autoantibodies to intermediate filaments in acute viral hepatitis A, B and non-A, non-B are directed against vimentin. AB - Using ELISA and immunoblotting, autoantibodies to vimentin were sought in sera from 10 patients with acute hepatitis A, 10 with acute hepatitis B, 13 with acute non-A, non-B hepatitis, 16 with autoimmune chronic active hepatitis, 17 with cytomegalovirus infection and 40 from healthy persons. The ELISA results were expressed as a percentage of the value obtained with a monoclonal antibody to vimentin. The results (mean and SD) for acute hepatitis A (51.2 +/- 21.7%), acute hepatitis B (44.5 +/- 28.2%) and acute hepatitis non-A, non-B (43.0 +/- 16.4%) were significantly (p less than 0.01) higher than those for autoimmune chronic active hepatitis (20.5 +/- 7.7%), cytomegalovirus infection (25.9 +/- 12.2%) and healthy controls (16.8 +/- 9.3%). Immunoblotting showed that sera from patients with acute viral hepatitis reacted with 57 kd vimentin in triton-cytoskeletal extracts of fibroblasts. These results show that autoantibodies to vimentin are present in sera from patients with acute hepatitis A, B and non-A, non-B. Antivimentin autoantibodies may be useful in the diagnosis of acute non-A, non-B hepatitis. PMID- 3084794 TI - Thyroid hormone antagonizes an aldosterone-induced protein: a candidate mediator for the late mineralocorticoid response. AB - In the urinary bladder of the toad Bufo marinus, the basal rate of synthesis of a number of proteins was modulated in a bidirectional way (i.e., induced or repressed) by aldosterone and by triiodothyronine (T3). Each hormone was therefore characterized by a distinct domain of response. When both hormones were added simultaneously, the two domains consistently overlapped at least for one protein, termed AIP-1, or aldosterone-induced protein 1 (Mr approximately 65 kilodaltons, pi = 6.7, as analyzed by two-dimension gel electrophoresis). The physiological role of AIP-1 is unknown, but could be related to the late mineralocorticoid response. In five experiments, T3 (60 nM, 18-hr incubation) consistently repressed AIP-1, while aldosterone-dependent sodium transport (late response) was significantly inhibited, as previously described. The repression of AIP-1 was also observed as early as 6 hr after aldosterone addition. In addition, sodium butyrate (3 mM), which was previously shown to also selectively inhibit the late mineralocorticoid response, was also able to repress AIP-1. Our results suggest that AIP-1 is one of the proteins involved in the mediation of the late mineralocorticoid response. PMID- 3084795 TI - Structure and evolution of the apolipoprotein multigene family. AB - We present the complementary DNA and deduced amino acid sequence of rat apolipoprotein A-II (apoA-II), and the results of a detailed statistical analysis of the nucleotide and amino acid sequences of all the apolipoprotein gene sequences published to date: namely, those of human and rat apoA-I, apoA-II and apoE, rat apoA-IV, and human apoC-I, C-II and C-III. Our results indicate that the apolipoprotein genes have very similar genomic structures, each having a total of three introns at the same locations. Using the exon/intron junctions as reference points, we have obtained an alignment of the coding regions of all the genes studied. It appears that the mature peptide regions of these genes are almost completely made up of tandem repeats of 11 codons. The part of mature peptide region encoded by exon 3 contains a common block of 33 codons, whereas the part encoded by exon 4 contains a much more variable number of internal repeats of 11 codons. These genes have apparently evolved from a primordial gene through multiple partial (internal) and complete gene duplications. On the basis of the degree of homology of the various sequences, and the pattern of the internal repeats in these genes, we propose an evolutionary tree for the apolipoprotein genes and give rough estimates of the divergence times between these genes. Our results show that apoA-II has evolved extremely rapidly and that apoA-I and apoE also have evolved at high rates but some regions are better conserved than the others. The rate of evolution of individual regions seems to be related to the stringency of their functional requirements. PMID- 3084796 TI - Differential distribution of lysine and arginine residues in the closely related histones H1 and H5. Analysis of a human H1 gene. AB - A human H1 histone gene and its flanking sequences were isolated from a human gene library using a fragment of the duck H5 histone gene as a hybridization probe. The primary structure of this human H1 histone (as deduced from the nucleotide sequence of the gene) reveals a close homology of H1 and H5 histones and fits the three-domain organization of all members of the H1 histone family. Within this protein organization, the C-terminal domain of H1 differs from the arginine-rich H5 in its distribution of the basic amino acids: the C-terminal domain of the human H1 shows only one arginine and most of the H5 specific arginine positions show lysine instead. PMID- 3084799 TI - Primary structure of the Paramecium tetraurelia small-subunit rRNA coding region: phylogenetic relationships within the Ciliophora. AB - We have sequenced the coding region for the small-subunit rRNA gene from Paramecium tetraurelia. Similarity comparisons between small-subunit rRNAs from representatives of the Metazoa, the Plantae, the Fungi and four other members of the Ciliophora were used to construct phylogenetic trees. In these phylogenies the Ciliophora diverged from the eukaryotic line of descent as a loose phylogenetic grouping during a radiative period that gave rise to the Fungi, the Plantae and the Metazoa. PMID- 3084798 TI - The cloning and characterization of a RAS gene from Schizosaccharomyces pombe. AB - We have cloned and determined the complete nucleotide sequence of a RAS gene from the yeast Schizosaccharomyces pombe (SP-RAS). The putative RAS protein of 214 amino acids is encoded by two noncontiguous reading frames separated by an intron of 86 bp. The SP-RAS gene product shares extensive homology with the proteins of the Saccharomyces cerevisiae (SC), Dictyostelium, Drosophila, and human RAS genes in its N-terminal region but not in its C-terminal region. The extended C terminal regions found in the SC-RAS genes have no counterpart in the SP-RAS gene. Thus the RAS genes of these two yeasts are structurally quite distinct. The SP-RAS sequence was expressed in vivo. PMID- 3084797 TI - Comparison of three actin-coding sequences in the mouse; evolutionary relationships between the actin genes of warm-blooded vertebrates. AB - We have determined the sequences of three recombinant cDNAs complementary to different mouse actin mRNAs that contain more than 90% of the coding sequences and complete or partial 3' untranslated regions (3'UTRs): pAM 91, complementary to the actin mRNA expressed in adult skeletal muscle (alpha sk actin); pAF 81, complementary to an actin mRNA that is accumulated in fetal skeletal muscle and is the major transcript in adult cardiac muscle (alpha c actin); and pAL 41, identified as complementary to a beta nonmuscle actin mRNA on the basis of its 3'UTR sequence. As in other species, the protein sequences of these isoforms are highly (greater than 93%) conserved, but the three mRNAs show significant divergence (13.8-16.5%) at silent nucleotide positions in their coding regions. A nucleotide region located toward the 5' end shows significantly less divergence (5.6-8.7%) among the three mouse actin mRNAs; a second region, near the 3' end, also shows less divergence (6.9%), in this case between the mouse beta and alpha sk actin mRNAs. We propose that recombinational events between actin sequences may have homogenized these regions. Such events distort the calculated evolutionary distances between sequences within a species. Codon usage in the three actin mRNAs is clearly different, and indicates that there is no strict relation between the tissue type, and hence the tRNA precursor pool, and codon usage in these and other muscle mRNAs examined. Analysis of codon usage in these coding sequences in different vertebrate species indicates two tendencies: increases in bias toward the use of G and C in the third codon position in paralogous comparisons (in the order alpha c less than beta less than alpha sk), and in orthologous comparisons (in the order chicken less than rodent less than man). Comparison of actin-coding sequences between species was carried out using the Perler method of analysis. As one moves backward in time, changes at silent sites first accumulate rapidly, then begin to saturate after -(30-40) million years (MY), and actually decrease between -400 and -500 MY. Replacements or silent substitutions therefore cannot be used as evolutionary clocks for these sequences over long periods. Other phenomena, such as gene conversion or isochore compartmentalization, probably distort the estimated divergence time. PMID- 3084800 TI - Comparative rates of esterification of 5'-AMP with hydrophobic amino acids: relevance to the genetic-code assignments. AB - We have continued our program aimed at understanding the origin and evolution of the genetic code and the process of protein synthesis by comparing the rates of esterification of 5'-AMP by a series of hydrophobic N-acetylamino acids. The reaction clearly shows differences in reaction rate (AcPhe greater than AcLeu greater than AcVal greater than AcIle) among the amino acids having A as middle letter of their anticodons. However, there were no significant differences in reaction rate between AcLeu, AcNorleu, and Ac-alpha-aminobutyric acid, and AcGly reacted faster than all of these and AcPhe. Consequently, this simple reaction with AMP can distinguish only among those amino acids that actually have A as the middle anticodonic nucleotide. The relevance of these studies to the origins of the process of protein synthesis and of the genetic code is discussed in conjunction with results from other studies of a similar nature. PMID- 3084801 TI - Pattern recognition of sequence similarities in globular proteins by Fourier analysis: a novel approach to molecular evolution. AB - A new algorithm is introduced for analyzing gene-duplication-independent (orthologous) and gene-duplication-dependent amino acid sequence similarities between proteins of different species. It is based on the calculation of an autocorrelation function D(x) as a Fourier series analogous to that used in crystal analysis by x-ray diffraction. The primary structure of the protein is decomposed into "homopolypeptide-defective sequences" containing identical or similar amino acid residues and vacancies corresponding to the missing amino acid residues. The Fourier transforms F(h) simulating the diffraction patterns of defective linear gratings corresponding to the defective homopolypeptide sequences are calculated. The squared F(h) values are then used as coefficients of Fourier series corresponding to the autocorrelation functions D(x). A peak of D(x) corresponds to a vector of length x, which is the distance between two identical amino acid residues. It is pointed out that optical diffraction methods, instead of computer methods, would also be useful. It is shown through a number of examples that this method allows satisfactory pattern recognition of homologies and internal duplications of an initial segment of the polypeptide chain. In the latter case the value of the above method may be seen from the fact that it detects repeated duplications in proteins such as spinach ferredoxin and myoglobin, for which other methods had either failed or given inconclusive results. The above approach appears most promising for studies of molecular evolution and structure-sequence correlations. PMID- 3084802 TI - Pulmonary interstitial fibrosis with evidence of aflatoxin B1 in lung tissue. AB - Three cases of pulmonary interstitial fibrosis, two in agricultural workers and one in a textile worker, are reported. In lung samples of all three patients the presence of aflatoxin B1 was demonstrated by radioimmunoassay (RIA). A possible occupational risk of aflatoxin exposure via the respiratory tract is suggested. PMID- 3084803 TI - Disodium cromoglycate, a mast-cell stabilizer, alters postradiation regional cerebral blood flow in primates. AB - Early transient incapacitation (ETI) is the complete cessation of performance during the first 30 min after radiation exposure, and performance decrement (PD) is a reduction in performance at the same time. Supralethal doses of radiation have been shown to produce a marked decrease in regional cerebral blood flow in primates concurrent with systemic hypotension and a dramatic release of mast-cell histamine. In an attempt to elucidate mechanisms underlying the radiation-induced ETI/PD phenomena and the postradiation decrease in cerebral blood flow, primates were given the mast-cell stabilizers disodium cromoglycate (DSCG) or BRL 22321 (Beecham Pharmaceuticals, Research Division) before exposure to 100 Gy whole-body gamma radiation. Hypothalamic and cortical blood flows were measured by hydrogen clearance, before and after radiation exposure. Systemic blood pressures were determined simultaneously. The data indicated that DSCG was successful in diminishing postradiation decrease in cerebral blood flow. Irradiated animals pretreated with DSCG, showed only a 10% decrease in hypothalamic blood flow 60 min postradiation, while untreated, irradiated animals showed a 57% decrease. The cortical blood flow of DSCG treated, irradiated animals showed a triphasic response, with a decrease of 38% at 10 min postradiation, then a rise to 1% below baseline at 20 min, followed by a fall to 42% below baseline by 50 min postradiation. In contrast, the untreated, irradiated animals showed a steady decrease in cortical blood flow to 79% below baseline by 50 min postradiation. There was no significant difference in blood-pressure response between the treated and untreated, irradiated animals. Systemic blood pressure showed a 60% decrease at 10 min postradiation, falling to a 71% decrease by 60 min. The effects of BRL 22321 in altering postradiation blood flow in the cerebral cortex and hypothalamus were intermediate between the irradiated controls and those pretreated with DSCG, but were not considered to be significant at the concentration employed. The overall results of this study indicate that the postradiation decrease in regional cerebral blood flow may be partially alleviated by treatment with a mast-cell stabilizer. PMID- 3084804 TI - Developmental features of rat cerebellar neural cells cultured in a chemically defined medium. AB - We studied some aspects of the differentiation of rat cerebellar neural cells obtained from 8-day postnatal animals and cultured in a serum-free, chemically defined medium (CDM). The ability of the cells to take up radioactive transmitter amino acids was analyzed autoradiographically. The L-glutamate analogue 3H-D aspartate was taken up by astroglial cells, but not by granule neurons, even in late cultures (20 days in vitro). This is in agreement with the lack of depolarization-induced release of 3H-D-aspartate previously observed in this type of culture. In contrast, 3H-(GABA) was scarcely accumulated by glial-fibrillary acidic-protein (GFAP)-positive astrocytes, but taken up by glutamate decarboxylase-positive inhibitory interneurons and was released in a Ca2+ dependent way upon depolarization: 3H-GABA evoked release progressively increased with time in culture. Interestingly, the expression of the vesicle-associated protein synapsin I was much reduced in granule cells cultured in CDM as compared to those maintained in the presence of serum. These data would indicate that in CDM the differentiation of granule neurons is not complete, while that of GABAergic neurons is not greatly affected. Whether the diminished differentiation of granule cells must be attributed only to serum deprivation or also to other differences in the composition of the culture medium remains to be established. 3H-GABA was avidly taken up also by a population of cells which were not recognized by antibodies raised against GFAP, glutamate decarboxylase, and microtubule-associated protein 2. These cells exhibited a stellate morphology, were stained by the monoclonal antibody A2B5, and have been characterized elsewhere [Levi et al, 1986] as bipotential precursors of oligodendrocytes and of a subpopulation of astrocytes bearing a stellate shape and capable of high affinity 3H-GABA uptake. PMID- 3084805 TI - Factors influencing DRG 210 (hip fracture) reimbursement. AB - The effect of prospective payment system (PPS) on reducing cost and quality of care is still unknown. Fifty-two patients (mean +/- SD, 82.0 +/- 6.5 years) with hip fracture classified as DRG 210 (hip and femur procedures except major joint, age greater than 69 years and/or complication and/or comorbidity), treated by compression nail were separated into four groups: Group I--no comorbidity, no complications; Group II--no comorbidity but had complications; Group III--with comorbidity but no complications; and Group IV--with both comorbidity and complications. Compared to length of stay (LOS) in Groups I, II and III (mean 26 days), Group IV had significantly increased LOS (mean, 61.5 days) and 81% of the 16 who were day outliers (L.O.S. greater than 40 days). Patients without comorbidity (I & II) even if they did develop complications were not financial losers. Those with comorbidity appear to be high-cost patients as they invariably end up with complications (78%), and reimbursement for Group IV was significantly less, resulting in net loss of this DRG. Our finding demonstrates the importance of preventing complications in patients with comorbidity. Present DRG reimbursement guidelines do not provide sufficient attention to LOS implications of both comorbidity and complications. Ideally, they should be considered as separate factors within the DRG category. PMID- 3084806 TI - Effect of fluosol-DA infusion on pulmonary vascular permeability in the dog lung. AB - Oxygen-carrying perfluorocarbon (PFC) emulsions show clinical promise as blood supplements or substitutes. However, some evidence suggests that PFC emulsions may accumulate in the lungs to disrupt pulmonary function. This study was conducted to determine whether the infusion of a PFC emulsion (Fluosol-DA) would alter microvascular permeability in the isolated canine right lower lung lobe (RLL). RLL's, perfused at constant pressure with autogenous blood, were divided into three groups: Group I (n = 6), the control group, was infused with bovine serum albumin (BSA) until the BSA solution equaled 10% of the total blood volume in the perfusion system; Group II (n = 6) was infused with Fluosol-DA until the emulsion comprised 10% of the final blood volume; and Group III (n = 6) was infused with Fluosol-DA until it comprised 20% of the final blood volume. The pulmonary filtration coefficient (Kf), an index of microvascular permeability, was obtained in each group approximately 1 hour after infusion. The Kf values for the control, 10% Fluosol, and 20% Fluosol groups were 0.070 +/- 0.018, 0.127 +/- 0.024, and 0.115 +/- 0.022 ml X min-1 X mm Hg-1 X 100 gm-1, respectively, and were not significantly different (p greater than 0.05) from each other. Perfusate oncotic pressure, lobar compliance, blood gas levels, and pulmonary arterial pressure did not vary significantly among the experimental groups. Under these experimental conditions, Fluosol-DA, in blood concentrations that might be used clinically, was not associated with an increased microvascular permeability in the isolated dog lung lobe. PMID- 3084807 TI - An esoteric occupational hazard for lead poisoning. AB - A case of life threatening lead poisoning was diagnosed clinically in a Jewish scribe and verified by appropriate laboratory studies. The special ink used by the scribe was found to contain lead in appreciable amounts. Eleven more asymptomatic subjects, both scribes and manufacturers of the ink, were studied and five were found to have subclinical lead overload. Handling or production of this ink is a potential hazard for lead intoxication. PMID- 3084808 TI - Nucleoprotein complexes of minute virus of mice have a distinct structure different from that of chromatin. AB - We studied the structure of viral nucleoprotein complexes extracted from the nuclei of mouse cells infected with the immunosuppressive strain of the minute virus of mice (MVMi). Two types of complex were detected, with sedimentation coefficients of about 110 and 40S. The complexes sedimenting at 110S contained single-stranded MVMi DNA as well as a second form of viral DNA which apparently had a heat-sensitive secondary structure. The 110S peak also contained proteins which coelectrophoresed with the MVMi capsid proteins. Complexes sedimenting at 40S contained the double-stranded replicative form of MVMi DNA. These complexes sedimented faster than did the pure replicative form DNA (15S), but more slowly than cellular chromatin fragments containing DNA of the same length. They incorporated labeled deoxynucleoside triphosphate in vitro into the replicative form DNA. We investigated the structure of MVMi nucleoprotein complexes in the following ways. Nuclei of MVMi-infected cells were digested with staphylococcal nuclease, and the resulting DNA fragments were electrophoresed, transferred to nitrocellulose, and hybridized first with labeled MVMi DNA and then with cellular DNA. A nucleosomal repeat pattern was seen with the cellular DNA probe but not with the MVMi DNA probe. The DNA in MVMi nucleoprotein complexes was cross-linked with psoralen, purified, denatured, and examined with an electron microscope. Bubbles, indicating the presence of proteins, were seen in the MVMi DNA. The length of the DNA in the bubbles was 90 +/- 29 nucleotides. On the other hand, nucleosomes protected 160 base pairs from cross-linking by psoralen. The MVMi nucleoprotein complexes thus have a distinct structure which is different from that of chromatin. PMID- 3084809 TI - Induction of Epstein-Barr virus nuclear antigens. AB - Lymphocytes were infected with the QIMR-WIL strain of Epstein-Barr virus, and the induction of Epstein-Barr virus-associated nuclear antigens was determined by using the protein immunoblot. There was a temporal increase in six antigens, with Epstein-Barr nuclear antigen 2 being detected 1 day after infection. The appearance of these antigens was shown to be independent of cellular DNA synthesis. PMID- 3084810 TI - The investigation of an unusual asphyxial death in a hospital. PMID- 3084811 TI - Luteinizing hormone releasing hormone analogue therapy for central precocious puberty. Long-term effect on somatic growth, bone maturation, and predicted height. AB - The long-acting analogue of luteinizing hormone releasing hormone, D-Trp6-Pro9 NEt-LHRH (LHRHa), is effective in the short-term treatment of central precocious puberty. We report the results of two to four years of LHRHa therapy in 27 children with this disorder. Secondary sex characteristics regressed in most patients. Sex steroid levels and basal and LHRH-stimulated gonadotropin levels remained suppressed compared with pretreatment values. Linear growth rates decreased from 11.0 +/- 0.8 (SEM) cm/yr before treatment to 5.7 +/- 0.4 cm/yr at two years of treatment and 3.7 +/- 0.7 cm/yr at four years of treatment. Predicted heights by the Bayley-Pinneau method increased from 156.4 +/- 2.0 cm before treatment to 162.3 +/- 2.3 cm at two years and 163.4 +/- 2.4 cm at three years. Five patients treated for four years had a mean increase in predicted height of 5.5 cm. To date no adverse effects have been observed. However, the ultimate safety of this analogue is not known. We conclude that LHRHa appears to be an effective long-term therapy for central precocious puberty. PMID- 3084812 TI - Diarrhoeal diseases. PMID- 3084813 TI - Helminthic infestation in Hazara Division. PMID- 3084814 TI - Infantile diarrhoea due to enteropathogenic E.coli. PMID- 3084816 TI - Hypokalaemia and urinary anomalies in children with diarrhoea in rural Bangladesh. PMID- 3084815 TI - Congenital diaphragmatic hernia in the adult. PMID- 3084817 TI - In vivo antibacterial activity of Berberis asiatica. PMID- 3084818 TI - Prevalence of intestinal parasites in diarrhoeal patients. PMID- 3084819 TI - Drug treatment in bronchial asthma. PMID- 3084820 TI - Management of patients with inguinal hernia. PMID- 3084821 TI - Surgical management of idiopathic upper gastro-intestinal haemorrhage. PMID- 3084822 TI - Normal shapes of liver: analysis of normal nuclear scans in Multan. PMID- 3084823 TI - Drug antibiotic interactions-antimalarials. PMID- 3084825 TI - Median cleft of the upper lip in association with frontonasal meningocele, left aniridia and lenticular opacity. PMID- 3084824 TI - Preparation of Tc 99m-Sn-thioglycolic acid-dl-isoleucine (Tc-99m-TGA-ILEU) complex and its comparison with Tl 201-chloride for myocardial imaging. PMID- 3084826 TI - [Sleep disorders--with special reference to the sleep apnea syndrome]. PMID- 3084827 TI - [Influence of hypertonic solutions on hemodynamics during intracranial operations]. PMID- 3084828 TI - [Heinz's body formation test on nitroglycerin treated blood]. PMID- 3084829 TI - [Antibacterial activity of (+)-negamycin prepared by a new method]. AB - Antibacterial activity of (+)-negamycin (NGM) prepared by a new method was investigated for some bacteria. The results demonstrated that this antibacterial activity of synthesized NGM was almost the same as compared to that of naturally obtained NGM, and was also effective to Pseudomonas aeruginosa harboring multiple drug resistant plasmid kR102. PMID- 3084830 TI - [Clinical studies on doxycycline in the treatment of nongonococcal urethritis by Chlamydia trachomatis]. AB - Twenty-one nongonococcal urethritis patients by Chlamydia trachomatis infection were treated with doxycycline (DOXY, Vibramycin) 200 mg/day orally for 2 weeks. The age of these patients were ranged from 17 to 52. C. trachomatis was eradicated 8(89%) of 9 cases on 3rd day and never reisolated on 7th day after treatment. Ten (83%) of 12 patients on 7th day and any patients on 14th day were not suffered from symptoms after treatment. Urethral discharge was not seen macroscopically, 11 (92%) of 12 patients on 7th day and any patients on 14th day. According to the criteria for urethritis requiring at least 4 WBC per high power field in urethral smear and/or first voided urine, the overall clinical efficacy rate was 44% (4/9) on 3rd day, 83% (10/12) on 7th day and 100% (9/9) on 14th day. No side effects were recognized in any cases. In conclusion, DOXY was thought to be useful and safe drug in the treatment of nongonococcal urethritis by C. trachomatis. PMID- 3084831 TI - [Platelet count in EDTA-dependent pseudothrombocytopenia--application of MgSO4 as an anticoagulant]. PMID- 3084832 TI - [Mannitol contrast enhancement CT in brain tumor]. PMID- 3084834 TI - [Effect of hepatic cytoplasmic protein on migration of Leu 2a+cell from the capillary tube]. PMID- 3084833 TI - [Intra-arterial embolization of microcapsulated mitomycin C in the treatment of advanced carcinoma]. PMID- 3084836 TI - [Response of gastric inhibitory polypeptide (GIP) and insulin release after a biliary reconstruction procedure or pancreaticoduodenectomy]. PMID- 3084835 TI - [Contrast effects of glucagon and effervescent granules on gastrointestinal MRI (magnetic resonance imaging)]. PMID- 3084837 TI - [Spontaneous closure of an esophageal perforation]. PMID- 3084838 TI - A piece of the action. PMID- 3084839 TI - Experimental gold nephropathy in guinea pigs: detection of autoantibodies to renal tubular antigens. AB - Renal tubular dysfunction was induced in Hartley guinea pigs by injection of sodium aurothiomalate (gold) as manifested by excretion of tubular basement membrane (TBM) antigen and renal tubular epithelial (RTE) antigen in urine and tubular proteinuria. Following the tubular dysfunction, autoimmune tubulointerstitial nephritis (TIN) and/or immune complex nephropathy (ICN) developed in a large proportion of animals. TIN was associated with anti-TBM antibodies, and the histological features were characterized by tubular lesions with interstitial mononuclear cell infiltration, destruction of tubules, and interstitial fibrosis. In ICN, the glomerular lesions consisted of partial thickening of capillary walls and mesangial cellularity, and granular immune deposits were seen in the mesangial area and on capillary walls. Furthermore, electron-dense deposits were demonstrated in the mesangial area and in the glomerular basement membrane (GBM) by electron microscopy. Anti-RTE antibodies were detected in the sera and eluates from the kidney of animals with ICN. RTE antigens were also detected in the glomerular deposits by indirect immunofluorescence using anti-guinea pig RTE antibody. These results suggest that TBM and RTE antigens released from renal tubules damaged by a direct toxic action of gold may lead to antibody formation against these antigens and induce TIN and/or ICN. PMID- 3084840 TI - [Treatment of patients with disorders of motor-evacuation functions of the intestines]. PMID- 3084841 TI - [Enteral feeding of surgical patients (review of the literature)]. PMID- 3084842 TI - [Current aspects of pancreas transplantation (review of the literature)]. PMID- 3084843 TI - [Enteral and parenteral feeding in the preparation of patients for abdominal operations]. PMID- 3084845 TI - [Effectiveness of tube feeding in burn injury patients]. PMID- 3084844 TI - [Unusual course of Recklinghausen disease in childhood--clinical and neuropathologic findings]. AB - The case-history of a child with von Recklinghausen disease is described: The patient suffered the following tumors: Olfactory nerv meningeoma, optic nerv glioma, acoustic nerv neurinoma, intraventricular meningeomas, intraspinal ependymoma and peripheral neurinomas. The pathogenesis (neurocristopathy) and aetiology are discussed. PMID- 3084846 TI - [Nursing of patients with cytostatic treatment]. PMID- 3084847 TI - [A fulfilled life--with cancer]. PMID- 3084848 TI - [The St. Joseph Hospice. Care of dying patients in London]. PMID- 3084849 TI - [Support and care of dying children and adolescents in their domestic environment and possibilities of support to their families]. PMID- 3084850 TI - [Support for the care-givers]. PMID- 3084851 TI - [Companion for the patients--approach to the truth]. PMID- 3084852 TI - [Emotionally wholesome conditions for cancer patients]. PMID- 3084853 TI - [Nutrition and neoplastic activity]. PMID- 3084854 TI - [Problems of recovered patients]. PMID- 3084855 TI - [Nursing personnel--roads out from helplessness]. PMID- 3084856 TI - [Message for World Health Day 1986: live healthy--it is worthwhile!]. PMID- 3084857 TI - [Living healthy--a challenge to all of us]. PMID- 3084858 TI - [Are support numbers settled by new calculation methods? Use of support numbers: computation of personnel needs oriented to nursing care categories. II]. PMID- 3084859 TI - [Concepts of management conditions on the basis of the professional nursing image of the German Nurses' Association]. PMID- 3084860 TI - [Insurance of need of care. Reports and opinions as reflected in the press]. PMID- 3084861 TI - [Critical observations on the financing of care in old age]. PMID- 3084862 TI - [Methods in ambulatory psychiatric care]. PMID- 3084863 TI - [Nursing report in the 2d study year (3d semester). Care of a terminally ill 60 year-old female patient]. PMID- 3084864 TI - [Geriatric care: health care cost risk--a private and a sociopolitical problem]. PMID- 3084865 TI - Susceptibility of tamarin (Saguinus labiatus) red blood cell membrane lipids to oxidative stress: implications for wasting marmoset syndrome. AB - Captive Callitrichids frequently suffer a fatal wasting disease, wasting marmoset syndrome (WMS), of unexplained cause. This paper describes studies on the erythrocytes from animals in a breeding colony of tamarins (Saguinus labiatus), in which deaths from anaemia and wasting were occurring, to seek evidence for biochemical changes which could lead to oxidative damage and premature cell lysis. In only one animal of 33 studied did the red blood cell lipids show an increased susceptibility to oxidative damage. This animal, with some degree of certainty, could be diagnosed as having WMS. It was concluded that evidence for a primary deficiency of antioxidants as a cause of unexplained deaths, or WMS, in the colony could not at present be substantiated. PMID- 3084866 TI - Prevalence of natural virus infections in laboratory mice and rats used in Canada. AB - Results of serological tests carried out over a period of 6 years to detect the presence of antibodies against 14 indigenous viruses in mice and rats used in 32 Canadian institutions are reported. Close to 20,000 individual sera were tested by the complement fixation or the hemagglutination inhibition technics. In order of mouse colony prevalence the six most common viruses present were pneumonia virus of mice, mouse hepatitis virus, rat virus, minute virus of mice, Sendai, and Theiler's mouse encephalomyelitis viruses. The most common viruses present in rat colonies were minute virus of mice, K virus, coronaviruses (rat coronavirus or sialodacryoadenitis virus), rat virus, H-1, pneumonia virus of mice, Theiler's mouse encephalomyelitis viruses, Sendai, and reovirus 3. PMID- 3084867 TI - Gelatin as a vehicle for food and vitamin administration to marmosets. AB - For a period of three years, gelatin was used as a vehicle for administration of food, vitamin complex and drugs to laboratory maintained Callithrix penicillata and Callithrix jacchus marmosets and a breeding colony of C. penicillata. In both circumstances, results were satisfactory. The animals survived for long periods of time, with adult, young and juvenile primates in the breeding colony showing good physical condition. PMID- 3084868 TI - Cost-effective antimicrobial therapy: an approach for physicians and community hospitals. PMID- 3084869 TI - What is "appropriate antimicrobial therapy"? PMID- 3084870 TI - High performance liquid chromatography of mycotoxin metabolites in human urine. AB - Because mycotoxins occur worldwide in grain and grain products, evaluating their effects on the health of the population has become important. The development of a high performance liquid chromatographic (HPLC) procedure was investigated for the analysis of aflatoxin B1, citrinin, and ochratoxin A, from hydrolyzed human urine. Solid-phase extraction (SPE) was used for sample clean-up and concentration. Reversed-phase liquid chromatography (RPLC) was used with fluorescence detection for sample analysis. The presence of aflatoxin B1 was confirmed by converting it to the hemiacetal. With 10 mL of urine, the detection limit for aflatoxin B1 and ochratoxin A was in the high parts per trillion (ppt) and that for citrinin was about 10 ppb. PMID- 3084871 TI - The effects of rate and route of nutrient intake on protein metabolism. AB - Isotopic measurements of protein kinetics are useful for the investigation of metabolic protein disorders during surgical illness. The effects of rate and route (oral vs parenteral) of nutritional substrate intake have not been well defined. Fischer 344 rats were infused with a total parenteral nutrition (TPN) solution at either 25, 100, or 175% of their normal substrate intake or were fed an oral diet ad libitum. After 4 days, [15N]glycine was infused at 0.138 mg 15N/hr for 24 hr. Whole-body protein turnover (WPT), synthesis, and catabolism were determined by 15N urea enrichment. Fractional synthesis rates (FSR) of liver and muscle protein were calculated by analyzing 15N tissue enrichment. WPT (r = 0.93, P less than 0.001) and liver FSR (r = 0.57, P less than 0.01) increased linearly with TPN infusion rates. All rats had protein synthesis rates greater than catabolism rates except for the rats infused with 25% TPN. Although caloric intake was the same in rats fed orally and those infused with 100% TPN, the orally fed rats had faster WPT (P less than 0.001), synthesis (P less than 0.05), catabolism (P less than 0.001), and liver FSR (P less than 0.05) than the TPN rats. Muscle FSR was not significantly affected by either the route of feeding or the TPN infusion rate. In this study, rate and route of substrate intake affected protein kinetics in the whole animal and liver, but not in muscle. Rate and route of nutrient intake need to be carefully specified and controlled during isotopic studies of protein kinetics. PMID- 3084872 TI - Intrinsic and extrinsic factors in estrogen action in human breast cancer: role of polyamines and pituitary factors. AB - Although polyamines are important in regulating proliferation of mammalian cells, their role in hormone induction of cell growth has not been delineated. In the estradiol-responsive human breast cancer cell line, T-47D clone 11, estradiol (10(-10) M) was able to stimulate cell proliferation and the activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of polyamines. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, blocked the estradiol-induced cell proliferation and ODC activity. Exogenous addition of putrescine, the natural product of ODC, rescued the inhibitory effect of DFMO. In addition, DFMO abolished the estradiol-induced growth of several other estrogen-responsive human breast cancer cell lines but did not affect the growth of hormone-independent cell lines. Further, a serum factor was found to be required for estradiol to exert its effect. To gain insight into the nature of this and possibly other extrinsic factors involved, the effect of estradiol on the proliferation of T-47D cells transplanted into athymic nude mouse was evaluated. In this in vivo system, estradiol alone produced only moderate growth of the human breast tumor. The simultaneous transplantation of a prolactin (PRL)- and growth hormone (GH)-secreting rat pituitary tumor or normal rat pituitary glands at a different site dramatically potentiated the effect of estradiol on the growth of the breast tumor xenograft. Purified PRL or GH were without effect, indicating that the active pituitary factor is neither PRL nor GH. Further, conditioned medium from rat pituitary tumor cells potentiated the mitogenic effect of estradiol on T-47D and several other estrogen receptor-positive human breast cancer cell lines in vitro under serum-free condition. In conclusion, we have identified both intrinsic (polyamines) and extrinsic (pituitary/serum) factors that are importance for estrogen to exert its mitogenic action. The next goal will be to elucidate the mechanisms of action of these molecules in the modulation of estrogen action. PMID- 3084873 TI - Paracrine control of Leydig cell activity by FSH dependent proteins from Sertoli cells: an in vitro study. AB - The regulating effect of follicle-stimulating hormone (FSH) on Leydig cell function was studied using a model of immature porcine Leydig and Sertoli cells cultured in a hormone supplemented defined medium. FSH pretreatment for 2 days of Leydig cells cultured alone was with no effect. FSH pretreatment of Leydig cells cocultured with Sertoli cells increases Leydig cell activity in an FSH dose dependent manner with a maximal effect observed at 50 ng/ml porcine FSH (pFSH). Leydig cells cultured for 2 days in conditioned medium (CM) by FSH stimulated (FSH-CM) Sertoli cells, as compared to CM by unstimulated (control) (C-CM) Sertoli cells show an increase of their activity with a maximal effect observed at 50 ng/ml pFSH. Leydig cells cultured in CM as compared to non CM, show a marked development of organelles (smooth endoplasmic reticulum and mitochondria) involved in the steroidogenic activity. The activity of FSH-CM as compared to C CM on Leydig cell function was non dialyzable and trypsin sensitive. These data suggest that Sertoli cells exert a regulatory action on Leydig cell steroidogenic activity via FSH dependent secreted proteins. PMID- 3084874 TI - Steroid regulation of gonadotropins in genetically hypoprolactinemic females (IPL nude rats). AB - IPL nude females present an absence of lactation with hypoprolactinemia. While males present a slight but significant decrease in serum testosterone and gonadotropins, females show normal values of estradiol, progesterone, LH and FSH during all estrus cycle stages. In this work, we observed that the postovariectomy rise of LH and FSH was significantly lower in the IPL nude females. We studied also the effect of acute (1 injection of 25 micrograms/rat E2Bz) or long-term (E2Bz capsule for 8 days) estradiol benzoate (E2Bz) treatment, with or without progesterone injection (5 mg/rat) in ovariectomized (OVX) IPL and normal females. The sensitivity of gonadotropins to E2 negative feedback is decreased in the IPL nude rats, result in agreement with previous reports and which could be linked to both hypoprolactinemia and decreased beta-endorphin observed in the IPL nude rat. The responsiveness of LH to LHRH was also tested in OVX and OVX + E2Bz or OVX + E2B + P treated. In OVX females responsiveness of LH to LHRH was similar in IPL nude to that of normal females. However, LH responsiveness in acute and long-term steroid-treated OVX IPL nude was significantly depressed. Since the mechanism whereby PRL interacts with steroids to modify gonadotropin secretion is still unexplained, IPL nude rat could be a good model to study it. PMID- 3084875 TI - Purification and immunological characterization of human placental mitochondrial cytochrome P-450. AB - Human placental mitochondrial cytochrome P-450 was purified to electrophoretic homogeneity by hydrophobic, anion exchange and cation exchange column chromatography. The specific content of the purified protein was 15.7 nmol/mg protein and it showed a single band mol. wt 48,000 D in SDS-gel electrophoresis. When reconstituted with bovine adrenal adrenodoxin reductase and adrenodoxin it converted cholesterol to pregnenolone (cholesterol side-chain cleavage activity, CSCC) at the rate of 1 pmol/min/pmol P-450. Antibodies against the purified protein were raised in rabbits. Inhibition studies demonstrated 85% inhibition of placental CSCC activity at an antibody/protein ratio of 10:1. Placental microsomal aromatase activity was inhibited by 47% at the same antibody/protein ratio. The antibody inhibited bovine mitochondrial CSCC activity by 87% at the same antibody/protein ratio. Placental microsomal 7-ethoxycoumarin O-deethylase, aryl hydrocarbon hydroxylase and 7-ethoxyresorufin O-deethylase activities were not significantly inhibited by the antibody. The results indicate that the purified protein catalyzes cholesterol side-chain cleavage reaction, human placental microsomal aromatase and bovine adrenal mitochondrial P-450scc may share common antigenic determinants with placental P-450scc, but the placental microsomal xenobiotic-metabolizing cytochrome(s) is (are) distinctly different. PMID- 3084876 TI - Reduced activity of androgen biosynthesis in the testes of rats with analbuminemia. AB - Steroid metabolism in Nagase Analbuminemia Rats (NAR), a mutant strain established from Sprague-Dawley rats, was studied. NAR are characterized by lack of serum albumin and hyperlipidemia. Total testosterone concentration in the serum of NAR was lower than that of normal rats, while the serum free testosterone, LH and FSH concentrations were similar. The half lives of 14C labeled testosterone administered intravenously in NAR and normal Sprague-Dawley (SD) rats were 4.4 and 4.1 min, respectively. The plasma clearance rates of testosterone in NAR and normal rats were 34.7 and 39.1 ml/min per kg body weight. On Sephadex G-100 chromatography, a mixture of [3H]testosterone and normal rat serum gave two protein peaks eluted in the void volume and the albumin fraction, and the radioactivity was eluted all in the albumin fraction. In contrast, a mixture of [3H]testosterone and NAR serum gave a single protein peak eluted in the void volume and the radioactivity was mainly eluted with this protein peak. The association constants of testosterone to NAR and normal rat sera were 1.25 and 2.24 X 10(4) M-1. Enzyme activities related to the synthesis of testosterone by the testicular microsomal fractions of NAR and normal rats were examined. The activities of 3 beta-hydroxysteroid dehydrogenase, 5-ene-4-ene isomerase, 17 alpha-hydroxylase, C-17-C-20 lyase and 17 beta-hydroxysteroid dehydrogenase were lower in NAR than in normal rats. The activity for synthesis of testosterone from pregnenolone by the testicular microsomal fraction of NAR was about 40% of that of normal rats. These findings indicate that the low serum concentration of testosterone in NAR is mainly attributable to decreased biosynthesis of testosterone in the testes. PMID- 3084877 TI - Twenty-four-hour monitoring of esophagopharyngeal pH in outpatients. Use of four channel pH probe and computerized system. AB - A 24 hour computerized four-channel esophagopharyngeal pH system is described. Using a 1.5 mm diameter esophageal probe containing four separate antimony-tipped electrodes and a small patient-worn digital recording computer, inpatient and outpatient studies are performed in the physiologic environment of the patient's workplace or home. Stored pH data in the computer are teletransmitted from satellite esophageal pH laboratories to a central esophageal pH laboratory for analysis, scoring, printout, and storage. Satellite laboratories located in hospitals, clinics, and physicians' offices use a minimum of equipment and obtain a quality computer-based printout. This preserves patient-physician relationships in the home environment and is cost-effective. Four case reports are presented identifying the advantages derived from the four-channel system localizing and quantifying the extent of cephalad transport of refluxed upper gastrointestinal content. The system has unique clinical and research potential in all age groups in such disparate problems as sleep apnea, laryngitis, bradycardia and cardiac irregularities, and aspiration pneumonia and pulmonary abscess. PMID- 3084878 TI - Ligand-specific calcium mobilization in IL 2 and IL 3 dependent cell lines. AB - Calcium mobilization is one of the earliest quantitative biochemical events associated with extracellular messenger stimulation of cellular proliferation. Therefore, purified recombinant lymphokines Interleukin 2 (IL 2) and Interleukin 3 (IL 3) were examined for ligand stimulation of calcium mobilization with highly specific interleukin-dependent cloned cell lines. Although IL 2 and IL 3 share neither amino acid structural homologies nor cellular tissue specificity, both recombinant polypeptides induced rapid influx of calcium into quiescent cells bearing specific receptors for the ligand. Neither ligand was capable of stimulating calcium mobilization in the non-homologous target cells which differed in tissue lineage. Stimulation of calcium mobilization demonstrated characteristic threshold dose-response kinetics and was observed under conditions where intracytoplasmic calcium levels were spontaneously depleted upon ligand deprivation. These data confirm that in addition to the activation of protein kinase C, growth regulatory polypeptides of mature T lymphocytes (IL 2) and hematopoietic stem cells (IL 3) share common biochemical features of the ligand receptor signal transduction apparatus which initiates cellular proliferation. PMID- 3084879 TI - The kinetic response of haemopoietic precursor cells, in vivo, to highly purified, recombinant interleukin-3. AB - Interleukin-3 is a murine haemopoietic cell growth factor which has now been prepared in recombinant form, rIL-3. This purified material has been shown to act, in vitro, in a comparable manner to the native material and has recently been shown to have an in vivo effect on the committed, in vitro colony-forming cells. We have examined the effects, in vivo, of low acute and chronic infusion doses on the pluripotent haemopoietic spleen colony-forming cells, CFU-S, (stem cells). The proliferation rate of CFU-S is rapidly increased after administration of rIL-3. This is followed by a migration of the more mature CFU-S to the spleen where, particularly under chronic rIL-3 treatment there is a large increase in CFU-S numbers. The increased proliferation of CFU-S is accompanied by increased differentiation in the form of a large increase in in vitro IL-3 responsive cells. The changes observed were not the result of endotoxin contamination in the rIL-3 preparation. Significantly, however, larger doses of lipopolysaccharide, did mimic the effects of rIL-3 in vivo. IL-3 was not detected in the blood following LPs treatment but it is suggested that LPS acts indirectly on haemopoietic precursor cells by eliciting local production of IL-3, perhaps from adjacent T cells or stromal cells. PMID- 3084880 TI - Paraquat-induced neutrophil alveolitis: reduction of the inflammatory response by pretreatment with endotoxin and hyperoxia. PMID- 3084881 TI - Prostaglandins and the lung. PMID- 3084884 TI - The postirradiated breast. AB - High-energy irradiation is used increasingly as a part of breast conservation treatment of malignant disease. The response of the breast tissue encompassed by the treatment fields varies considerably, even in well-conducted therapeutic programs. Early and late changes in the tissues include redness, edema, pigmentation, fibrosis, and retraction. Fibrosis and retraction may cause suboptimal cosmetic results and occur most frequently in obese patients, large breasts, and breasts from which a large (greater than 4 cm) primary tumor has been excised. Combinations of treatment modalities, such as adjuvant chemotherapy, surgical excision, and irradiation, seem to produce fewer excellent cosmetic results than single-modality treatment. In patients who have undergone breast conservation treatment, careful follow-up is necessary for detection of possible local, regional, or distant recurrence of the malignant disease, as well as of other diseases related or unrelated to the earlier treatment. PMID- 3084883 TI - Comparison of three platelet markers for measurement of platelet survival time in healthy volunteers. AB - We studied mean platelet survival times in healthy volunteers with use of [51Cr]disodium chromate, 111In-oxine (in a solution of acid-citrate-dextrose [ACD] and saline), and 111In-tropolone (in ACD-plasma) as markers. Differences found between the 51Cr and 111In labels probably can be attributed to a variation in localization of the label on the cell and of renal handling of the free label after release. The mean platelet survival time with 51Cr was slightly longer than the survival time with both indium labels and showed a sex difference not seen with 111In-oxine. Protein-bound plasma 51Cr was lower than plasma 111In and remained constant throughout the study. Plasma 111In increased with time. For survival time calculations, no correction for free 51Cr is necessary, but correction should routinely be performed when 111In markers are used. Both 111In markers gave similar results with respect to platelet survival time. The somewhat more elaborate plasma labeling procedure with tropolone shows no measurable advantage over the original 111In-oxine method. 111In-tropolone labeling takes less time and maintains platelets in the physiologic environment of plasma during incubation. Biodistribution studies show no difference between the two 111In markers. PMID- 3084882 TI - Cough: physiology, evaluation, and treatment. PMID- 3084885 TI - Regulation of primate testicular function by GnRH analogues. AB - The potential of GnRH analogues for regulating testicular function is reviewed. Our experiments showed that constant infusion of GnRH agonists effectively suppressed testicular function in monkeys. In men, however, spermatogenesis could not be suppressed to achieve azoospermia uniformly. GnRH antagonists, although at much higher dosages than agonists, caused a more rapid and uniform inhibition of testis function. Spermatogenesis was reversibly disrupted at the spermatogonial level. Concomitant testosterone supplementation, used to maintain libido and potency, attenuated the antitesticular effects of GnRH analogues. In monkeys testosterone appears to stimulate spermatogenesis directly on the testicular level, while evidence has been obtained that in rats testosterone can also stimulate the release and synthesis of FSH under antagonist mediated blockage of pituitary GnRH receptors. When extrapolating to human studies special care has to be exerted in the selection of testosterone substitution regimens. Although the agonistic and antagonistic analogues of GnRH ultimately exert their antireproductive effects via inhibition of gonadotropin secretion the antagonists may have the greater potential for male fertility regulation due to quicker pituitary and testicular suppression. PMID- 3084886 TI - Cell interactions in the rat seminiferous epithelium with special reference to the cellular distribution of calmodulin. AB - Spermatogenesis is dependent on stimulation by pituitary gonadotropins, FSH and LH. Targets for these hormones are Sertoli and Leydig cells, respectively. The effect of LH on spermatogenesis is mediated by testosterone. In addition to hormones, interactions between neighbouring cells seem to regulate spermatogenesis. This is reflected by cyclic secretion of several proteins by the seminiferous epithelium, of which plasminogen activator is a good example. While it is controlled by FSH a factor in preleptotene spermatocytes may also influence its cyclic secretion pattern. Both testosterone and FSH have a cyclic action in the seminiferous epithelium. The androgens seem to predominate in stages where spermiation, onset of meiosis and the highest rate of RNA transcription occur (VII-XI). FSH is most active in stages that contain meiotic divisions and early spermiogenesis (XIII-V), greatly stimulating the production of cyclic AMP. To investigate further the "second messengers" of FSH action in the seminiferous epithelium, the cellular distribution of calmodulin was analyzed using an indirect immunocytochemical method. In addition to their clear cyclic distribution in primary spermatocytes and in spermatids, Sertoli cells also showed a bright calmodulin immunofluorescence that was apparently cyclic. These observations suggest a local calmodulin and calcium regulation of spermatogenesis. PMID- 3084887 TI - Predicting posttrauma functional disability for individuals without severe brain injury. AB - The utility of the Abbreviated Injury Scale (AIS), the most widely used anatomic scale for rating severity of injuries, and its derivative for assessing the combined effect of multiple injuries, the Injury Severity Score (ISS), were tested for their ability to predict functional disability at time of discharge from the hospital and 6 months after discharge. The ISS has been shown to correlate well with mortality and length of stay, but the relationship to levels of subsequent disability has not been examined. Five hundred and ninety-seven patients (aged 16-45 years) were interviewed at time of discharge and 6 months after discharge to ascertain functional disability along three dimensions: activities of daily living (ADL), instrumental activities of daily living (IADL), and mobility. The authors report on the relationship between severity and functional disability at time of discharge and 6 months after discharge for a subset of 473 patients who did not suffer a severe brain injury. The results show that the relationship between ISS and status at discharge and 6 months after discharge is not monotonically increasing, as it is with mortality and length of stay (LOS). Rather, the proportion of people with severe injuries who report limitations is lower than for those with moderately severe injuries as defined by the ISS. Further, it is shown that the AIS of the most severe extremity and spinal cord injury carry considerably more weight when predicting functional status at discharge and 6 months after discharge than do the AIS scores of injuries to any other body region, although the relative explanatory power of each type of injury varies with the nature of the functional disability and the time interval between the initial insult and assessment. PMID- 3084888 TI - Variation in resource use within diagnosis-related groups. The effect of severity of illness and physician practice. AB - The diagnosis-related group (DRG)-based Medicare prospective payment system pays hospitals a fixed amount for the care of similar patients. The DRG definitions serve as the modifier of payment for Medicare patients. The dependence on these patient definitions raises many questions, among them the reason(s) for observed resource variability within a DRG. Various severity-of-illness measures have been shown to account for some of the resource variability noted within the DRGs. Most severity-of-illness studies to date, however, have not attempted to assess the effect of other known sources of resource variation, such as differing physician practice patterns. The authors examined the ability of severity of illness, as defined by disease staging, and physician practice variation to explain residual intra-DRG variability in length of stay. They demonstrate that physician practice variation accounts for more variance reduction than does severity of illness. PMID- 3084889 TI - An alternative to DRGs. A clinically meaningful and cost-reducing approach. AB - A statistical methodology based on the Cox proportional hazards model (a survival time analysis method), an alternative to the approach underlying DRGs, is presented. The method is used to obtain an estimate of the length-of-stay (LOS) distribution of a patient incorporating either patient-specific or hospital variables. A percentile of the distribution chosen to minimize prediction error serves as the assigned LOS. Absolute deviation is used as the loss function both to determine the choice of a predicted LOS and to examine how well the scheme works. Multiple assignment schemes may also be developed from this approach. The results of the method, tested on a national probability sample of 4,608 psychiatric patients treated in psychiatric units of general hospitals, suggest that with respect to average absolute deviation, the proposed methodology may provide a scheme that is superior to the present DRG scheme. For the sample, the average percent improvement obtained using the median of the estimated LOS distribution as the predicted LOS over the sample mean of the DRG group is 19%. A two assignment strategy results in average improvements over DRGs of 43%. PMID- 3084890 TI - [Total parenteral nutrition in severe flare-ups of intestinal inflammatory disease]. PMID- 3084891 TI - [Gonadal dysfunction in the male with chronic renal insufficiency]. PMID- 3084892 TI - [Exacerbation of psoriasis by lithium carbonate: apropos of a case]. PMID- 3084893 TI - [Intravenous nitroglycerin infusion in patients with acute heart failure]. PMID- 3084894 TI - Effects of retinoic acid treatment on release of arachidonic acid by chondrogenic cells in response to ionophore A23187. AB - Chondrogenic differentiation in mouse limb bud mesenchymal cells cultured at high density was suppressed by supplementation of the medium with retinoic acid in a dose-dependent fashion. Cells prelabeled with (3H) arachidonic acid were treated with 0.3 microgram/ml retinoic acid. Treatment with retinoic acid increased the (3H) fatty acid in the triglyceride fraction. Furthermore, treatment with retinoic acid enhanced the release of (3H) fatty acid upon stimulation of these cells with the divalent ionophore A23187. These data permit the suggestion that there may be a correlation between altered lipid metabolism and retinoic acid's ability to disrupt chondrogenic differentiation. PMID- 3084895 TI - Prevention of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic toxicity in mice by MDL 72145, a selective inhibitor of MAO-B. AB - Pretreatment of mice with the potent and selective monoamine oxidase B (MAO-B) inhibitor MDL 72145 ((E)-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine) protected against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). Mice treated with MDL 72145 prior to MPTP did not exhibit the decrement in the neostriatal content of dopamine and its metabolites normally seen after MPTP administration. This observation adds further support to the concept that the oxidation of MPTP by MAO-B to its corresponding pyridinium analog, 1-methyl-4-phenylpyridinium (MPP+), is an important feature of the neurotoxic process. PMID- 3084896 TI - Vasopressor responses and hypoxemia with acutely increased intracranial pressure. AB - We studied anesthetized dogs subjected to graded increases in intracranial pressure (ICP) to assess the role of the systemic vasopressor (Cushing) response in the arterial hypoxemia associated with increased ICP. The arterial PO2 decrement was significantly greater with rapidly increased ICP compared to slowly increased ICP (P less than 0.01). Systemic vasopressor responses generated in cats by direct electrical stimulation of the vasomotor center resulted in arterial hypoxemia during controlled ventilation. Therefore, arterial hypoxemia was coincident with increased systemic blood pressure produced by either elevation of ICP or electrical stimulation of the vasomotor center. PMID- 3084898 TI - Induction and growth of mammary tumors after superior cervical ganglionectomy in sighted and blinded-anosmic rats. AB - Female rats were subjected to superior cervical ganglionectomy (Gx), blinding and anosmia (BAs) or combined procedures (BAsGx). Onset and growth of dimethylbenz(a)anthracene (DBMA)-induced mammary tumors was studied in these animals and compared to tumorigenesis in intact control rats. Carcinostatic effects were present in all surgically altered animals, as evidenced by a trend toward reduced tumor incidence, reduced final tumor mass, and a significant reduction in mean number of tumors in Gx and BAsGx rats, and increased regression of tumors in BAs rats compared to intact group. Reduced tumorigenesis was paralleled by a trend toward either an increase (BAs) or a decrease (Gx and BAsGx) in the activity of pineal hydroxyindole-O-methyltransferase (HIOMT) compared to intact group. In addition, BAs and BAsGx animals showed a significant reduction in body weight. These results suggest that Gx reduces mammary tumorigenesis in both sighted and BAs rats. They further confirm the findings of others on reduced mammary tumorigenesis in BAs rats. Possible involvement of multiple carcinostatic mechanisms in different animal models is discussed. PMID- 3084897 TI - Uteroglobin inhibits phospholipase A2 activity. AB - Although progesterone is known to produce quiescence in the mammalian uterus, the mechanism of this effect is not clearly understood. Here, we report that uteroglobin, a progesterone-induced small molecular weight (16K) protein, inhibits phospholipase A2(PLA2) derived from porcine pancreas as well as from the RAW 264.7 macrophage cell line. We speculate that progesterone may exert its antimotility effects on the uterus via uteroglobin which, by inhibiting PLA2, decreases arachidonic acid release and subsequently reduces prostaglandin levels in this organ. This may explain why progesterone is so vital for the maintenance of pregnancy in almost all mammals. PMID- 3084899 TI - Pressor effect of centrally administered neuropeptide Y in rats: role of sympathetic nervous system and vasopressin. AB - The haemodynamic effects of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY) in urethane-anaesthetized rats were studied. In Sprague Dawley rats, NPY increased both blood pressure and heart rate in a dose-dependent manner. This response was unaffected by removal of the adrenal medullae or pretreatment with a specific vasopressin antagonist (180 ng/kg i.v.), but was abolished by phenoxybenzamine (1mg/kg i.v.). After pretreatment with propranolol (1mg/kg i.v.), the tachycardia was inhibited and the pressor response was of shorter duration than in controls. In 6-hydroxydopamine treated rats (two doses of 250 micrograms i.c.v., three days apart), NPY still elicited a pressor response and tachycardia, which were significantly higher than controls 15 minutes after the injection. Plasma levels of vasopressin were not altered by i.c.v. administration of NPY. However, in Brattleboro rats the peptide had no haemodynamic effects. Our results suggest that activation of sympathetic nervous system but not release of vasopressin or adrenal catecholamines into the bloodstream mediates the cardiovascular response to NPY. Central vasopressin pathways however may be involved. PMID- 3084901 TI - Physician income and its sources: Maryland. PMID- 3084902 TI - Inpatient management protocols to reduce health care costs. AB - A group of 12 internists, members of a university-affiliated hospital, designed and implemented protocols for the general inpatient management of four medical problems (chest pain, stroke, pneumonia, and upper gastrointestinal hemorrhage). Hospital charges for the 63 cases were compared with charges generated by 64 controls who had been patients admitted to the same physicians with the same diagnoses during the same period of the preceding year, before the project was begun. A group of nonparticipating internists was similarly evaluated during the two time periods to control for changes in practice patterns extraneous to the intervention. Adjustment was made for inflation (6%) and differences in case mix. The program resulted in a 15% reduction in total average charge generated by the cases. Sizeable reductions were achieved in utilization of EKGs (34.8%), x-rays (15.4%), laboratory testing (20.4%), and drugs (11.4%). Given the prevailing attitude that health care costs are too high and that many services are unnecessary, the benefit of altering physician behavior by using standards established by them for themselves could be substantial, especially with the threat of more restrictive and less sympathetic modes of controlling costs. PMID- 3084900 TI - Dexamethasone blocks arachidonate biosynthesis in isolated hepatocytes and cultured hepatoma cells. AB - The effect of dexamethasone on the incorporation and conversion of [1-14C]eicosa 8,11,14-trienoic acid to arachidonic acid in isolated hepatocytes and in hepatoma tissue culture (HTC) cells was studied. In both kinds of cells, no changes in the exogenous acid incorporation were found when the hormone was added to the incubation media at 0.1 or 0.2 mM concentration, while the biosynthesis of arachidonic acid was significantly depressed. The effect on the biosynthesis was faster in isolated normal liver cells (60 min) than in tumoral cells (120 min) and reached an inhibition of ca. 50% after 3 hr of treatment. The addition of cycloheximide (10(-6) M) also caused a marked decrease in the biosynthesis of this polyunsaturated fatty acid, but when dexamethasone was added to the media simultaneously with cycloheximide, a synergistic action was not observed. The results obtained show that protein synthesis would be involved in the modulation of the biosynthesis of arachidonic acid by glucocorticoids. The changes in the delta 5 desaturation of labeled 20:3 omega 6 to arachidonic acid correlated with changes in the fatty acid composition in isolated cells. PMID- 3084903 TI - [Chemotherapy trial in the battle against Schistosoma haematobium in an irrigated sahelian zone in Niger]. AB - This study of S. haematobium infection in communities associated with irrigated schemes shows that prevalence rates are unusually high in adults, especially in men; and distribution disease is probably associated with at least the following three factors: (i) distance of the place of residence from the main transmission sites (ii) the dynamics of transmission in the waterbody and (iii) the human/water contact and contamination patterns. During this chemotherapy trial, at the first survey, only a little more than half (57.47%) of the people recorded in the census was present. Five visits of the survey team were necessary to obtain a compliance rate of 80.51% of the entire population. The indifference of the local people to seek diagnosis and treatment increased with succeeding surveys. It is only, during a subsequent treatment survey, carried out during the season of low agricultural activity and following an official written convocation, that a compliance rate similar to that of the first survey was recorded. If treatment is not given immediately after diagnosis as many as a fifth of positive cases do not appear for treatment. Oltipraz and praziquantel were administered. Their effectiveness could not be truly compared as there was a time lag of six months separating the administration of the treatments. However, based on the results of this trial both drugs gave good results especially in egg output intensity. But, a decrease of this parameter was also observed in non treated people. Seasonal variations of egg output or decrease of transmission could be involved. PMID- 3084904 TI - Determinants of plasma potassium levels in diabetic ketoacidosis. AB - The classic proposal of intracellular K+ for extracellular H+ exchange as responsible for the hyperkalemia of diabetic ketoacidosis (DKA) has been questioned because experimentally induced organic anion acidosis fails to produce hyperkalemia. It has been suggested, instead, that the elevated serum [K+] of DKA might be the result of the compromised renal function, secondary to volume depletion, that usually accompanies DKA. However, several metabolic derangements other than volume depletion and acidosis, which are known to alter potassium metabolism, also develop in DKA. This study of 142 admissions for DKA examines the possible role of alterations in plasma pH, bicarbonate, glucose (G), osmolality, blood urea nitrogen (BUN) and plasma anion gap (AG) on the levels of [K+]p on admission. Significant (p less than 0.01) correlations of [K+]p with each of these parameters were found that could individually account for 8 to 15 percent of the observed variance in the plasma potassium levels; however, the effects of some or all of these parameters on the [K+]p could be independent and therefore physiologically additive. Since the parameters under study are themselves interrelated, having statistically significant correlations with each other, their possible independent role on [K+]p was evaluated by multiple regression analysis. Only plasma pH, glucose and AG emerged as having a definite independent effect on [K+]p, with no independent role found for bicarbonate, BUN and osmolality. The equation that best describes [K+]p on admission for DKA was: [K+]p = 25.4 - 3.02 pH + 0.001 G + 0.028 AG, (r = 0.515). These results indicate that the endogenous ketoacidemia and hyperglycemia observed in DKA, which result primarily from insulin deficit, are the main determinants of increased [K+]p. Since exogenous ketoacidemia and hyperglycemia in the otherwise normal experimental animal do not increase [K+]p, it is postulated that insulin deficit itself may be the major initiating cause of the hyperkalemia that develops in DKA. Renal dysfunction by enhancing hyperglycemia and reducing potassium excretion also contributes to hyperkalemia. PMID- 3084905 TI - Left-sided endocarditis due to Pseudomonas aeruginosa. A report of 10 cases and review of the literature. AB - Ten confirmed cases of left-sided endocarditis due to Pseudomonas aeruginosa were reported in detail and the English literature was reviewed. In recent years, venous access (usually illicit) has been the major predisposing factor to this infection and abuse of pentazocine and tripelennamine has been particularly associated with endocarditis due to this organism. This infection involves previously damaged as well as normal valves. The development of congestive heart failure did not adversely affect the prognosis of this infection. However, the development of azotemia was associated with a greater likelihood of a fatal outcome. In the current series, deaths were due to uncontrolled infection. This often occurred despite inhibitory and bactericidal activity in serum generally considered adequate for treatment of endocarditis. Medical treatment alone rarely produced cure of infection. Our experience with a high frequency of major vessel embolization (4/10) and the improved survival after medical/surgical treatment suggests that prompt valve replacement combined with high doses of an aminoglycoside plus carbenicillin or ticarcillin provide the best opportunity for successful outcome in patients with left-sided endocarditis due to P. aeruginosa. PMID- 3084906 TI - Long-term changes in cholesterol biosynthesis and the effect of plasmapheresis therapy in a hypercholesterolemia homozygote. AB - Synthesis of cholesterol was measured in a familial hypercholesterolemia homozygote on four occasions from age 1.1 to 9.9 years by the sterol balance technique. Both the fecal neutral steroid and fecal bile acid components of sterol balance were elevated initially. Over the decade of study, neutral steroid excretion/kg declined 61% whereas bile acid excretion/kg was unchanged. Chronic plasmapheresis therapy every two weeks for 3.4 years reduced plasma low-density lipoprotein cholesterol 54% but had little effect on the rate of cholesterol biosynthesis. PMID- 3084907 TI - Polyribosome concentration in human skeletal muscle after starvation and parenteral or enteral refeeding. AB - Posttraumatic and septic states cause a loss of body proteins resulting in a negative nitrogen balance. The major part of the excreted nitrogen is derived from the proteins of skeletal muscle. The loss in proteins is due to a decrease in protein synthesis rather than an increase in protein degradation. Nutritional support may increase protein synthesis, and determination of its activity in skeletal muscle will give information on the utilization of nutrients in catabolic patients. The effect of nutritional support on healthy subjects was studied to achieve a background for future clinical studies. Male volunteers between 20 and 40 years old were refed parenterally or enterally after three days of starvation. Muscle biopsies (50 mg) were analyzed for the size distribution of ribosomes in a sucrose density gradient, and the ribosome concentration was determined per mg of DNA. Changes in the percentage content of polyribosomes preceded those of the total ribosome concentration. The total polyribosome concentration per gram wet weight of skeletal muscle decreased significantly during starvation. After one and two days of refeeding, a significant increase was observed, but the original level of the nonstarved subjects was not reached. The total ribosome concentration increased upon refeeding, but was not significantly different from that of the starved condition. The nitrogen balance was negative during starvation but attained equilibrium after two days of refeeding. Nutrition administered by the parenteral or enteral route were equally effective in restoring protein synthesis. PMID- 3084908 TI - Phospholipid-sensitive Ca2+-dependent protein kinase from bovine thyroid: characteristics and subcellular distribution of the enzyme and its substrates. AB - Ca2+-phosphatidylserine-dependent protein kinase activity was demonstrated in whole thyroid homogenates, cytosol, particulate, and membrane fractions. Although Ca2+-phospholipid-dependent protein kinase was difficult to detect in purified thyroid plasma membranes, an EGTA extract of such membranes had this activity. While phosphatidylinositol did not stimulate the enzyme, it enhanced the response to phosphatidylserine in the presence of 10 mmol/L free Ca2+. The enzyme was active at concentrations of free Ca2+ as low as 1 mumol/L but was inhibited at Ca2+ in excess of 500 mumol/L. Bovine thyroid contained endogenous substrates of 38,000 and 33,000 daltons for thyroid or purified spleen Ca2+-phospholipid dependent protein kinase. The 38,000 dalton polypeptide was present in all the subcellular fractions while the 33,000 dalton substrate was present only in the whole homogenate and cytosolic fraction. The 38,000 dalton polypeptide, like the Ca2+-phospholipid-dependent protein kinase, was released from thyroid plasma membranes by EGTA. Phosphorylation of this substrate was rapid, highly sensitive to Ca2+, and inhibited by chlorpromazine (100 mumol/L) and trifluoperazine chlorpromazine (100 mumol/L) and trifluoperazine (100 mumol/L). Several substrates of a phospholipid-independent, Ca2+-dependent protein kinase with molecular weights of 51,000, 76,000, and 96,000 were also observed. This Ca2+ phospholipid-dependent protein phosphorylation system may be important in the membrane-associated functions of the thyroid. PMID- 3084909 TI - Heavy riboflavin synthase from Bacillus subtilis. PMID- 3084910 TI - Membrane-associated folate transport proteins. PMID- 3084912 TI - Separation of methotrexate analogs containing terminal lysine or ornithine and their dansyl derivatives by high-performance liquid chromatography. PMID- 3084911 TI - High-performance liquid chromatographic separation of the naturally occurring folic acid derivatives. PMID- 3084913 TI - Pantothenase-based assay of pantothenic acid. PMID- 3084915 TI - Fluorometric assays for avidin and biotin. PMID- 3084916 TI - Synthesis of carnitine precursors and related compounds. PMID- 3084914 TI - Bacterial folylpoly(gamma-glutamate) synthase-dihydrofolate synthase. PMID- 3084917 TI - Assessment of social value in the allocation of CT scanners--a case study. PMID- 3084918 TI - Handling, labeling, and fractionating sea urchin spermatozoa. PMID- 3084919 TI - Scanning electron microscopy of embryos. PMID- 3084921 TI - Allelism within the DEX and STA gene families in Saccharomyces diastaticus. AB - Saccharomyces diastaticus produces an extracellular glucoamylase and is therefore capable of hydrolyzing and fermenting starch. Tamaki (1978) studied starch utilization in S. diastaticus and found three polymeric genes controlling this function: STA1, STA2 and STA3. Independently, Erratt and Stewart (1978) studied dextrin utilization by the yeast S. diastaticus and designated the gene, which they identified, DEX1. Erratt and Stewart (1981 a, b) later described two other genes which controlled glucoamylase production in S. diastaticus: DEX2 and a third which was allelic to STA3. At that time STA1 and STA2 were not available to test for allelism in the DEX gene family. In this study strains containing the remaining 4 genes have been examined to determine if further allelism exists between the two gene families. It was ascertained that DEX1 is allelic to STA2 and DEX2 is allelic to STA1. Therefore, no new gene controlling starch utilization has been identified and these two nomenclatures can now be consolidated into one. Based on the fact that the glucoamylase from S. diastaticus can hydrolyze both dextrin and starch, dextrin being the term used to describe partially hydrolyzed starch, and the more wide use of the nomenclature STA, we propose to retain STA as the designation for genes coding for glucoamylase production in S. diastaticus. PMID- 3084920 TI - Two classes of Bacillus subtilis mutants deficient in the adaptive response to simple alkylating agents. AB - Six mutant strains of Bacillus subtilis hypersensitive to N-methyl-N'-nitro-N nitrosoguanidine (MNNG) were shown to be deficient in the adaptive response to MNNG and termed ada mutants (Morohoshi and Munakata 1985). All the mutations mapped between the attSPO2 and lin loci on the chromosome. The mutant and wild type (ada+) cells contained similar constitutive levels of O6-methylguanine-DNA methyltransferase activity. Pretreatment with low concentrations of MNNG increased the activity about nine-fold in the ada+ cells, while it uniformly decreased the activity in the ada cells. The pretreatment of three mutants (ada 3, ada-4, and ada-6) as well as ada+, augmented the activity of methylpurine-DNA glycosylase and rendered the cells resistant to the lethal and mutagenic effects of N-propyl- or N-butyl-N'-nitro-N-nitrosoguanidine. With the rest of the mutant strains (ada-1, ada-2, and ada-5), neither of such responses was elicited by the pretreatment. Thus, the former ada strains seem to have a defect in the gene specifically involved in the induction of the methyltransferase, while the latter ada strains have a defect in the gene controlling the adaptive response as a whole. PMID- 3084922 TI - Oestrogen production and metabolism in peri-menopausal women. AB - The metabolic clearance rates and production rates of oestrone and oestradiol have been measured in a group of peri-menopausal women either with breast or endometrial cancer or having an increased risk of developing one of these diseases. The results were compared with values for normal post-menopausal women in whom the menopause was established. The transfer constants for the conversion of oestrone to oestradiol and of oestradiol to oestrone were also measured. Metabolic clearance rates for oestrone (1946 +/- 406 1/24 h) and oestradiol (1296 +/- 261 1/24 h) for peri-menopausal women, and production rates of oestrone (90 +/- 38 micrograms/24 h) and oestradiol (45 +/- 33 micrograms/24 h) were significantly higher than for normal post-menopausal women. Transfer constants for the conversion of oestrone to oestradiol and of oestradiol to oestrone were similar in the peri- and post-menopausal women. Plasma progesterone concentrations were less than 0.4 ng/ml in both groups of women. It is possible that the higher oestrogen production and clearance rates of peri-menopausal women, at a time when progesterone production is greatly reduced, may in part account for the higher risk that post-menopausal women have for developing breast or endometrial cancer. PMID- 3084923 TI - Purification and immunochemical properties of a protein antigen from serotype g Streptococcus mutans. AB - A proteinaceous antigen (PAg) was purified from the culture supernatant of Streptococcus mutans 6715 (serotype g) by ultrafiltration, ammonium sulfate precipitation, DEAE-Sephacel ion-exchange chromatography, Phenyl-Sepharose CL-4B hydrophobic chromatography, and subsequent Sephacryl S-300 gel filtration. A yield of 0.1 mg of PAg was obtained from a liter of culture supernatant. The isoelectric point and molecular weight of PAg were pH 4.6 and 210,000, respectively. It contained 35% sugar, which was identified as glucose by gas liquid chromatography. Amino acid analysis revealed that PAg contains 28% acidic and 11% basic amino acid residues. PAg retained its antigenicity after heating at 80 C for 10 min in deionized water, or after treatment with 0.1 M HC1 or 0.1 M NaOH at 37 C for 1 hr. Immunodiffusion and immunoelectrophoresis analyses revealed that PAg is serologically distinct from other cell-surface antigens such as serotype-specific polysaccharide and lipoteichoic acid. A cross-reaction between PAg and a protein antigen similarly prepared from serotype c S. mutans was observed in immunodiffusion tests. PMID- 3084925 TI - [Distribution of microorganisms lysing Pseudomonas aeruginosa in reservoirs and soil]. AB - Various natural habitats were found to contain microorganisms producing lytic spots around their own colonies when grown on a lawn of viable Pseudomonas aeruginosa cells at 29 and 45 degrees C. The incidence of such microorganisms in water and soil was studied in quantitative terms. Contaminated waters with predominating Gram-negative heterotrophs and a high number of pseudomonades were shown to be an optimal source for the isolation of microorganisms causing the lysis of P. aeruginosa growing at 29 degrees C. Microorganisms responsible for the lysis of P. aeruginosa at 45 degrees C are abundant in the soil of mixed and foliage forests. PMID- 3084924 TI - Interferon-gamma induction in human peripheral blood mononuclear cells by OK-432, a killed preparation of Streptococcus pyogenes. PMID- 3084927 TI - Ulcer disease etiopathogenesis: an eclectic theory. AB - An eclectic theory of ulcer etiopathogenesis is presented. Its objective is to give a rational explanation to most of the disturbances and changes occurring in ulcer patients. The theory highlights the intricate cellular mechanisms which keep the balance between acid aggression and mucosal defense. The new theory presented here will serve as the skeletal framework upon which new biomedical and biopsychosocial development can be added to improve and expand the scientific explanation of why and how ulcers are formed. PMID- 3084926 TI - [Effect of the exogenous lipids of complex media on the fatty acid composition of mycelial microorganisms]. AB - The effect of exogenous lipid sources on the composition of fatty acids was studied in actinomycetes of the Streptomyces genus and in fungi belonging to the genera Blakeslea, Cunninghamella and Penicillium. The following sources of exogenous lipids were used: soybean and maize flour, sunflower by-products, chicken droppings, maize extract, yeast extract, peptone, sperm whale fat, sunflower and palm oil. The composition of fatty acids in total extracted lipids of the studied mycelial microorganisms was shown to reflect two processes: lipid synthesis de novo and assimilation of exogenous fatty acids. This fact ought to be taken into account both in the chemotaxonomic interpretation of fatty acid composition and in practical recommendations for the utilization of microbial lipids. It is of particular interest to study the physiological role of exogenous lipid metabolism in the cells of microorganisms. PMID- 3084929 TI - Lead as surface bolus for high-energy photon and electron therapy. AB - Dose distributions were evaluated under thin sheet lead used as surface bolus for 4- and 10-MV photons and 6- and 9-MeV electrons using a parallel-plate ion chamber and film. A narrow, significantly low dose region (-17%) was noted for 4 MV photons, whereas a 6% increase in dose was present for 10-MV photons. The dose was elevated 15%-22% near the surface of electron fields with lead bolus, but depth dose relationships were similar to soft-tissue-equivalent (STE) bolus. Investigation of partial-field bolus (2-cm-diam circle) documented reduced doses due to lack of lateral electron equilibrium for 10-MV photons, which was less evident using lead, and large edge effects (up to 30%) for electrons using either lead or STE bolus. Dose distributions on sloped surfaces with electron fields were similar for lead and STE; both require thickness adjustment to achieve a desired effective thickness normal to the surface. Lead bolus has been used successfully in clinical practice for photons. PMID- 3084928 TI - Buildup/surface dose and exit dose measurements for a 6-MV linear accelerator. AB - The central axis dose distribution in the buildup region for the Varian Clinac 6/100 6-MV x-ray beam was measured in a polystyrene phantom using a fixed volume (0.5 cm3) parallel-plate ionization chamber (2.4-mm plate separation). Results for the surface dose measurements ranged from approximately 8% of the maximum dose for a 5 X 5 cm field, up to 36% for a 40 X 40 cm field, 100-cm source-skin distance. The effect of a 0.6-cm-thick polycarbonate blocking tray and metal filters on the surface and buildup dose is also reported. In addition, ionization measurements were made to document the dose perturbations caused by the absence of backscattering material at the exit surface of a polystyrene phantom. Exit dose measurements showed a 15% reduction in dose with essentially no scattering material beyond the measurement point. Near full scatter condition could be restored by placing 5-10 mm (depending on field size) of unit density material directly behind the ion chamber's distal surface. PMID- 3084930 TI - Expenditures for the medical care of elderly people living in the community in 1980. AB - Policy debates about financing medical care for the elderly are often clouded by evidence drawn from averages based on aggregate data. The National Medical Care Utilization and Expenditure Survey enables examination of the circumstances of the 95 percent of the elderly who are not institutionalized. A significant portion of out-of-pocket charges falls on the poor; public expenditures are highly concentrated for the relatively few elderly in their last year of life. Medicare and Medicaid have successfully lessened the burden on families. PMID- 3084932 TI - Family care of the elderly: the role of public policy. AB - There is little evidence to support the belief--and many policy initiatives flowing from it--that families are less willing or able to provide home care to elderly relatives. Informal care-giving remains at a high level; institutionalization rates have changed little over the past 30 years. But some demographic trends affecting both the elderly and families may change this picture in the future. Proposals for providing cash grants or tax allowances do not get to the heart of the matter. PMID- 3084931 TI - Philosophical origins of the economic valuation of life. AB - Cost-benefit analysis--applying economic reasoning to increasingly complex health policy decisions--continues to be a source of vehement disagreement among its practitioners. re than merely technical issues in measurement and accounting are involved; basic social values embedded in different intellectual traditions are coming into conflict. The "human capital" and "willingness-to-pay" approaches can each aid policy formulation, but neither can substitute for open political process. PMID- 3084933 TI - [Growth recovery in a group of infants treated with total parenteral nutrition for chronic malnutrition]. PMID- 3084934 TI - [Central parenteral nutrition in newborn infants of body weight lower than 1500 grams. Metabolic and nutritional problems]. PMID- 3084935 TI - [Short bowel syndrome in neonates and infants. General considerations, personal cases and clinical follow-up]. PMID- 3084936 TI - National birthweight-specific infant mortality surveillance: preliminary analysis -United States, 1980. PMID- 3084937 TI - Ammonia contamination in a milk processing plant--Wisconsin. PMID- 3084938 TI - Rubella vaccination during pregnancy--United States, 1971-1985. PMID- 3084939 TI - Ectopic pregnancy--United States, 1981-1983. PMID- 3084940 TI - Horsemeat-associated trichinosis--France. PMID- 3084942 TI - Seat belt use--United States. PMID- 3084941 TI - Blood lead levels among office workers--New York City. PMID- 3084943 TI - Plasmid-mediated tetracycline-resistant Neisseria gonorrhoeae--Georgia, Massachusetts, Oregon. PMID- 3084944 TI - Campylobacter outbreak associated with raw milk provided on a dairy tour- California. PMID- 3084945 TI - Excavation cave-in fatalities--Texas, 1976-1985. PMID- 3084946 TI - Update: measles--Canada, 1986. PMID- 3084947 TI - [DNA interaction with the antitumor agent thiophosphamide]. AB - DNA interaction with an alkylating antitumor drug N,N',N" triethylenethiophosphoramide (thiotepa) in water-salt solutions at 37 degrees C has been studied by UV-spectroscopy, heat denaturation and electron microscopy methods. Changes of the DNA melting curve parameters provide information on the kinetics of alkylation. The dependence of the alkylation rate on DNA and thiotepa concentrations shows that the alkylation reaction is biomolecular. The increase of sodium chloride concentration from 10(-3) to 10(-1) M is accompanied by a drastic decrease of the alkylation rate. Thiotepa binding results in destabilization of the DNA secondary structure and formation of cross-links. An increased amount of bounded thiotepa results in DNA denaturation; prolonged alkylation causes breaks in the sugar-phosphate backbone. The results of the work are discussed in connection with the literature data on DNA interaction with thiotepa in vivo. PMID- 3084948 TI - Isolation and purification of the human thymocyte antigens T6 and M241. AB - T6 and M241 antigens are products of the Class I major histocompatibility complex. The T6 and M241 antigens can be detected on human cortical thymocytes and on dendritic cells in the skin by monoclonal antibodies. Here we report a method of purification of the T6 and M241 antigens. Amino acid sequence data of purified antigens indicate that the heavy chains are blocked at their N-termini, whereas the partial N-terminal amino acid sequence of the light chains is identical to that of the human beta 2-microglobulin. In order to obtain sequence data from the heavy chains a method is described for isolation of purified cyanogen bromide fragments by electrophoretic methods. PMID- 3084949 TI - The site of cleavage in human alpha chains of IgA1 and IgA2:A2m(1) allotype paraproteins by the clostridial IGA protease. AB - Fc fragments of human immunoglobulin A(IgA) of IgA1 subclass and IgA2 subclass of A2m(1) allotype were prepared from IgA paraproteins by digestion with a protease from Clostridium sp. (M.O.-6). The N-terminal tetrapeptide of Val-Pro-Ser-Thr- for the Fc of IgA1 subclass, and that of Val-Pro-Pro-Pro- for the Fc of IgA2:A2m(1) allotype, were identified by sequence analysis. The site of cleavage by the protease was defined to be at the Pro-Val peptide bond, which is a common peptide bond present at 221-222 in both alpha chains. IgA of IgA2 subclass of A2m(2) allotype is resistant to the protease due to the different, Arg-Val, peptide bond at the same position. PMID- 3084950 TI - Amino acid sequence of the variable region of heavy chain in immunoglobulin (Mot) having unusual papain cleavage sites. AB - An IgGl(lambda) Mot myeloma protein showed a unique susceptibility toward papain digestion. The Fab fragment of Mot was more digestible with papain than the Fc fragment. This phenomenon was found to occur by unusual cleavage of the Fd fragment with papain. Determination of the complete primary structure of the V region of the H chain of Mot identified two papain cleavage sites in the second complementarity-determining region (CDR). Amino acid sequence of the cleavage sites was Ser(55)-Asp-Asp-Argdecrease-Thr-Thr-Tyr-Gly-Pro-Argdecrease- Ser-Gln- (decrease = cleavage site). In the vicinity of these cleavage sites, many hydrophilic and polar residues are present and the predicted secondary structure near these cleavage sites suggested that this region was exposed on the surface of the molecule, and that the unusual papain cleavage of the IgG Mot might be caused by a unique conformation of the molecule, making it highly susceptible to enzyme digestion. PMID- 3084951 TI - [Induction of puberty by pulsatile luteinizing hormone releasing hormone (LH-RH)- therapy in a boy with Kallmann syndrome]. AB - To induce the lacking development of puberty, a male patient with hypothalamic hypogonadism and anosmia (Kallmann's syndrome) was treated with pulsatile application of gonadotropin-releasing hormone (GnRH) to imitate the endogenous secretion of GnRH. The low-dose pulsatile GnRH treatment which was reported to be successful by various authors proved to be ineffective when administered to our patient subcutaneously as well as intravenously. Serum testosterone levels comparable to the lower normal values in adults and continuous progress of pubertal development were only achieved after increasing the dosage from 2 to 8 micrograms per pulse by subcutaneous application. The course of therapy is reported in detail. PMID- 3084952 TI - [Type I glycogenosis: extending therapy with uncooked cornstarch]. AB - Normal or slightly elevated blood lactate levels and normal to slightly elevated lactate-/creatinine-ratios in 24-h-urine were found in 12 patients (0.9 to 16 years) with glycogenosis type I under conventional treatment with nocturnal gastric drip feeding with maltodextrine combined with frequent daytime feedings. Replacing the nocturnal gastric drip feeding by two doses of uncooked cornstarch suspended in water (single dose 1.4-2.0 g/kg body weight) 4 patients at the ages of 10 to 16 years obtained similar metabolic control. A 7-year old patient with glycogenosis type Ib showing an extremely low fasting tolerance attained stable blood glucose levels by eating two doses of uncooked cornstarch in the morning, so that she was able to attend school. A 2-year old patient received 2-3 g cornstarch/kg body weight every 6 h resulting in constant blood glucose levels, so that she was able to emigrate to Turkey. The therapy with uncooked cornstarch is suitable to augment the therapy of some patients with glycogenosis type I. PMID- 3084953 TI - [Angelman syndrome]. AB - An eight-year-old boy with Angelman-(Happy Puppet-)Syndrome is described. Nearly all typical symptoms of the syndrome, especially severe psychomotoric retardation with spontaneous outbursts of laughing and protrusions of the tongue, athetoid movements, typical electroencephalogram and microcephaly, could be found in our patient. The incidence of the Angelman-syndrome may be underestimated. PMID- 3084954 TI - [Intravenous infusion of reproterol (a beta-2-mimetic agent) in the therapy of severe asthma attacks in childhood]. AB - 20 children (age range 0.8-14.7 years) with acute severe asthma were alternately randomized to receive one of two different treatment regimes. 10 children (control-group) received Salbutamol inhalation (75 micrograms/kg in 2 ml Saline every two hours). 10 children (reproterol-group) received reproterol infusion (0.2-2.0 micrograms/kg/min in Saline) and inhaled Saline only. Other therapy regimen were identical in both groups: Theophylline infusion, i.v. Prednisolone, adequate fluids intake and oxygen insufflation. Age, severity and maintenance therapy of asthma, and severity of the acute episode, were not significantly different in both groups. Treatment efficacy, assessed with a simple clinical score, the heart and respiratory rates, the peak expiratory flow (PEF) and the blood gases, was comparable in both groups. Side effects, i.e. tachycardia, blood pressure changes and tremor, were also similar and clinically not relevant in both groups. In two children, who previously needed repeated mechanical ventilation, severe respiratory failure could be successfully controlled only when the reproterol dose was raised 10 folds (2.0 micrograms/kg/min). Reproterol infusion can be recommended in children with acute severe asthma, who do not respond satisfactorily to current therapy regimen, particularly in children who previously experienced numerous intubations. PMID- 3084956 TI - Immune genes. PMID- 3084955 TI - Effect of lymphoma grafts on natural killer cell activity in AKR and C57BL/6 mice. AB - The natural killer (NK) cell activity of spleen suspensions was measured in AKR and C57BL/6 mice grafted either with isogeneic thymic or nonthymic lymphomas. The transplanted cells originated from lymphoid tumors (B, T, or null) which developed either spontaneously (AKR) or after radiation exposure or after injection of retroviruses (C57BL/6). The NK response was significantly enhanced in AKR and C57BL/6 mice grafted with nonthymic and with some thymic lymphoma lines maintained by in vivo passages. The increase of NK activity which took place during the first 5 days after grafting was concomitant with a hyperplasia of the spleen red pulp. Cells from invaded spleens presented a suppressive effect on NK activity. Most primary AKR thymomas and 4 out of 8 tested thymic lymphomas maintained by in vivo passage in C57BL/6 mice were not inducers. In vitro passaged lymphomas, whether AKR or C57BL/6, displayed variable capacity of stimulation which did not match those of the same in vivo maintained lines. It was found that the capacity of most cultured cells to stimulate NK activity correlated positively with the reverse transcriptase concentration of the corresponding culture media. PMID- 3084957 TI - Regulation of immunoglobulin variable-region gene assembly. PMID- 3084958 TI - The Igh-V gene repertoire of the mouse. PMID- 3084959 TI - Production of novel immunoglobulin molecules by gene transfection. PMID- 3084960 TI - Structure and function of murine class II major histocompatibility complex genes. PMID- 3084961 TI - Major histocompatibility complex class II antigens: genes and proteins. PMID- 3084962 TI - Immunoglobulin genes and the c-myc oncogene in plasmacytomagenesis. PMID- 3084963 TI - Transgenic mice in immunology. PMID- 3084964 TI - Excision repair of DNA in the presence of aphidicolin. AB - During excision repair of UV light or dimethyl sulphate (DMS)-induced damage to DNA the patch size for actively replicating KB or T98G cells is around 20 nucleotides. When confluent T98G cells or 'quiescent' KB cells are used the patch size is around 10 nucleotides. This value can be increased to around 20 nucleotides in T98G cells if a large excess of BrdUrd is included in the repair incubation medium. With 'quiescent' KB cells the patch size is not increased by excess BrdUrd. For all of these experimental conditions, when excision repair of UV or DMS damage takes place in the presence of aphidicolin, the patch size is found to be several times that found in its absence. Given the inhibitory specificity of aphidicolin for DNA polymerase alpha these results provide additional evidence that DNA polymerase alpha plays a role in the excision repair of DNA damaged by UV light or DMS. It is postulated that aphidicolin interrupts the processivity of the DNA polymerase alpha holoenzyme and allows an exonuclease to enlarge the repair site. PMID- 3084965 TI - Excision repair in xeroderma pigmentosum group C but not group D is clustered in a small fraction of the total genome. AB - DNA repair in xeroderma pigmentosum complementation groups C and D occurs at a low level. Measurements of pyrimidine dimers remaining in bulk DNA from the whole genome indicated very little excision in either complementation group. The repair sites in group C cells were, however, clustered together in small regions of the genome which appeared to be mended nearly as efficiently as the whole genome is mended in normal cells, while repair in group D cells was randomly distributed. Growth of normal cells in cycloheximide or 3-aminobenzamide neither inhibited repair nor altered the distribution of repair sites. Growth of normal cells in novobiocin or aphidicolin inhibited excision but repair remained randomly distributed. On the basis of these observations, and consideration of other cellular features of group C and D, we suggest that group C may represent a mutation which results in a low level of repair enzymes with normal function. Group D, on the other hand, may represent a mutation resulting in functionally defective repair enzymes. PMID- 3084966 TI - Effects of temperature on chemically induced sister-chromatid exchange in human lymphocytes. AB - Lymphocytes from healthy adults were studied for sister-chromatid exchanges (SCEs) when pulse-treated in G0 with mitomycin C (MMC), ethyl methanesulfonate (EMS), or 4-nitroquinoline N-oxide (4NQO) at various temperatures ranging from 0 degrees C to 41 degrees C and then cultured in medium containing 5 bromodeoxyuridine at 37 degrees C. The results showed that the frequencies of SCEs induced by MMC or EMS varied according to the treatment temperature. In MMC- or EMS-exposed cultures, the SCE frequency increased continuously with increasing treatment temperature; treatment at 37 degrees C resulted in a 3-4 times greater induction of SCEs than did that at room temperature (25 degrees C). On the other hand, SCE frequencies in cells exposed to 4NQO remained within normal deviation, showing no temperature-dependent changes. Baseline SCE frequencies remained almost constant within the temperature range tested. These data indicate that treatment temperature is a very critical factor in determining the sensitivity of cells to the chemical induction of SCEs. PMID- 3084968 TI - Not for women only. PMID- 3084967 TI - Chemical induction of sister-chromatid exchanges in human lymphocytes treated in G0 prior to stimulation by different mitogens and revealed 72 h later in second division cells. AB - Frequencies of sister-chromatid exchanges (SCE) were determined in second division metaphases of human lymphocytes, exposed for 1 h during the G0 phase to mitomycin C (MMC) alone or to cyclophosphamide (CP) in the presence of S9 mix. The cells were then cultured for 72 h in the presence of phytohemagglutinin (PHA), concanavalin A (Con A), Wistaria floribunda (WFA) or Lens culinaris (LcH A) extracts. Large differences in mitotic indices (MI) and cell-cycle kinetics were observed among cells subjected to the various treatments. However, in the controls as well as in the cultures submitted to a G0 mutagenic exposure, the yield of SCE was not influenced by the mitogenic agent and was, therefore, independent of the proliferation properties of the cultured lymphocyte population. PMID- 3084969 TI - Canadian birthing rooms and centers: a status report. PMID- 3084970 TI - Calcium paradox in skeletal muscles: physiologic and microscopic observations. AB - Immersion of rat hemidiaphragms in Ca2+-free Krebs solution (KS) containing Ca2+ chelator in vitro leads to separation of basal lamina from the plasma membrane, as well as transient contracture and rapid loss of twitch response [calcium paradox (CP) phase 1]. Subsequent immersion in regular KS results in necrosis of muscle fibers accompanied by slowly increasing contracture (CP phase 2). This contracture could be prevented or reduced by using either Ca2+-free KS or calcium channel blockers, but not by dantrolene sodium, implying that after drastic reduction of extracellular and sarcolemmal Ca2+ during CP phase 1, the sarcolemma has lost its ability to control normal Ca2+ fluxes. Contracture did not develop at 21 degrees C. CP is a convenient model to study calcium-induced muscle cell death and the role of Ca2+ in maintaining sarcolemmal integrity. PMID- 3084972 TI - [The repeated isolation of Candida pulcherrima (Lindner) Windisch from blood cultures of a patient on parenteral nutrition]. PMID- 3084971 TI - Serum carbonic anhydrase III in myotonic dystrophy. AB - Serum carbonic anhydrase III (CAIII) levels were determined by means of an enzyme immunoassay method and were compared with serum creatine kinase (CK) and muscle specific enolase (MSE) levels in 33 patients with myotonic dystrophy. Serum CAIII levels were elevated in all 33 patients, whereas serum CK and MSE levels were elevated in 12 and 10 patients, respectively. Serum CAIII levels showed a good correlation with CK levels, but a poor one with MSE levels. There was no obvious correlation between the serum CAIII level and the duration of illness or the age of the patient. These results suggest that serum CAIII is probably a more sensitive marker than CK and MSE in myotonic dystrophy and may also reflect the type 1 fiber abnormality more predominantly observed in myotonic dystrophy. PMID- 3084973 TI - Lupus anticoagulant and AIDS. PMID- 3084974 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 19-1986. An 18-year-old man with hypertension and narrowing of the abdominal aorta. PMID- 3084975 TI - Psychiatric consultation in somatization disorder. A randomized controlled study. AB - The per capita expenditure for health care of patients with multiple physical symptoms but no apparent physical disease (somatization disorder) is up to nine times the average per capita amount. We conducted a randomized controlled trial to determine whether psychiatric consultation would reduce the medical costs of these patients, without effecting a substantial change in patient outcome. Thirty eight patients were randomly assigned to treatment or control groups and studied prospectively for 18 months. Treatment consisted of a psychiatric consultation and suggestions on management given to primary physicians. After nine months, the control group was crossed over to receive treatment with the same intervention. After the psychiatric consultation, the quarterly health care charges in the treatment group declined by 53 percent (P less than 0.05). In contrast, the charges in the control group showed wide variations but no overall change. The quarterly charges in the control group were significantly higher than those in the treatment group (P less than 0.05). After the control group was crossed over to receive treatment, their quarterly charges declined by 49 percent (P less than 0.05). The reductions in expenditures in both groups were due largely to decreases in hospitalization. We conclude that psychiatric consultation in the care of patients with somatization disorder reduced subsequent health care expenditures without inducing changes in health status or patients' satisfaction with their health care. PMID- 3084976 TI - Early experience with prospective payment of hospitals. PMID- 3084977 TI - Immunology: development and modification of the lymphocyte repertoire. PMID- 3084978 TI - [Monitoring of resistance against Neisseria gonorrhoeae in 1983 and 1984]. PMID- 3084979 TI - [The stopping of food and fluid administration to patients]. PMID- 3084980 TI - High-affinity uptake of taurine and beta-alanine in primary cultures of rat astrocytes. AB - The kinetics and specificity of taurine and beta-alanine uptake were studied in primary cultures of rat astrocytes under identical experimental conditions. The uptake consisted of nonsaturable penetration and saturable high-affinity transport that was strictly sodium dependent. The cells accumulated taurine more effectively than beta-alanine, both the affinity and uptake capacity being greater for taurine. Taurine uptake was competitively inhibited by beta-alanine and GABA, the former being more potent. Also, hypotaurine and 2 guanidinoethanesulphonic acid strongly reduced taurine uptake, but L-2,4 diaminobutyric acid had no significant effect. beta-Alanine uptake was also competitively inhibited by GABA, but the most potent inhibitors were hypotaurine and 2-guanidinoethanesulphonic acid. L-2,4-Diaminobutyric acid was moderately active. The uptake systems for taurine and beta-alanine were thus in principle similar, and they exhibited certain characteristics typical for a neurotransmitter amino acid. The inhibition studies further suggest the existence of only one common transport system for taurine, beta-alanine, and GABA in cultured primary astrocytes. The same uptake system may also be used for hypotaurine. PMID- 3084981 TI - UDP-galactose: ceramide galactosyltransferase of rat central nervous system myelin during development. AB - The activity of UDP-galactose:hydroxy fatty acid containing ceramide galactosyltransferase was studied in the myelin and microsomal fractions of rat cerebral hemispheres, cerebellum and spinal cord during development. In all three regions, the specific activity of the enzyme reached a maximum in myelin prior to that in the microsomal membranes. This temporal relationship between myelin and microsomal fraction was similar in all the three regions, although the overall timing was shifted corresponding to known differential timing of myelin deposition in these regions. The activity of the enzyme from both the membranes, during development, increased in parallel with temperature up to 45 degrees C. Specific localization of galactosyltransferase in early myelin may suggest specific role of the enzyme in the myelination process. PMID- 3084982 TI - On the mechanism of fasting-associated elevations in hypothalamic cyclo(His-Pro) content. AB - Potential mechanism(s) underlying the fasting-associated rise in hypothalamic cyclo(His-Pro) content was explored by examining the effects of 24-hour fasting on: (i) cyclo(His-Pro) synthesis from TRH, (ii) cyclo(His-Pro) metabolism, and (iii) cyclo (His-Pro) secretion by hypothalamic tissue in vitro. The data presented here show that none of these three variables were altered due to fasting. Two additional potential changes that could cause cyclo(His-Pro) elevations during fasting are suggested. These include an in vivo decrease in hypothalamic cyclo(His-Pro) secretion that may not be apparent in vitro, and/or an increase in the synthesis of cyclo(His-Pro) from a precursor(s) other than TRH. PMID- 3084984 TI - [Surgical treatment of AVMs occluding these feeders during removal--utilizing the intraoperative balloon catheter and brain protective substances ("Sendai cocktail"]. AB - The ideal treatment of cerebral arteriovenous malformations (AVMs) is thought to be the total resection of nidus. We have been reporting the importance of temporary occlusion of the feeding arteries with the aid of the brain protective substances to prolong the permissible time of occluding these arteries. Because of the difficulty of access to the feeding arteries, some cases are difficult or even impossible to operate. In this communication, four cases of AVM which were successfully resected utilizing intraoperative balloon occlusion of feeders under the administration of the brain protective substances are reported. Case 1. A 14 year-old female was admitted to our clinic because of subarachnoid hemorrhage with ventricular rupture and left cerebellar hemorrhage. Angiography disclosed a large left cerebellopontine angle AVM fed by left anterior inferior cerebellar artery (AICA) and left superior cerebellar arteries (SCAs). Prior to the operation, two balloon catheters were introduced via transfemoral approach; one into the AICA and the other into the basilar artery where left SCAs originated. To prolong the permissible time of occluding these arteries, "Sendai cocktail" (20% mannitol, vitamin E and dexamethazone) and perfluorochemicals were administered. Auditory brain stem response (ABR) was monitored continuously during the operation. The nidus was resected totally with safe using temporary inflation of these balloon catheters. The patient returned to normal life. Case 2. A 35-year-old male was admitted to our clinic complaining of the attack of generalized convulsive seizure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084983 TI - Enzymes of the purine metabolism in rat brain microsomes. AB - Rat brain microsomes, when they are suspended in moderate ionic strength medium, released enzyme activities of lactate dehydrogenase (LDH, E.C.1.1.1.27), malate dehydrogenase (MDH, E.C.1.1.1.37), adenosine deaminase (ADA, E.C.3.5.4.4), guanine deaminase (GAH, E.C.3.5.4.3), and purine nucleoside phosphorylase (PNP, E.C.2.1.2.4). The activities released decreased when the saline concentration of the medium was increased and the opposite occurred when 50 mM, pH 7.4 sodium phosphate medium was used. Rat brain microsomes that had been extracted previously by moderate ionic strength solutions still had activities of all the enzymes tested, and released these activities upon sonication or deoxycholate (DOC) treatment. The proportion of the activity released was similar for all the enzymes. DOC treatment released higher enzymic activities and a smaller amount of protein than sonication did. The proportion of activities released was similar to that found in the 105,000 g supernatant. The suspension of microsomes still retained activities of the above-mentioned enzymes after consecutive extractions with increasing concentrations of detergent solutions (DOC and Triton X-100). The amount of enzymic activities released from the microsomes by sonication or DOC treatment did not depend on the protein composition of the homogenization medium. Thus, on increasing the enzyme concentration in the homogenization medium, the activities released did not increase in parallel. The set of results obtained showed that the microsomal fraction is as useful as the cytosolic one for studying purine catabolism in rat brain. Furthermore, the conditions in which purine enzymes are attached to the microsomal fraction are probably closer to "in vivo" conditions than those in which these enzymes are found in the soluble fraction. PMID- 3084985 TI - [A successfully treated case of giant basilar artery aneurysm utilizing balloon catheter occlusion and brain protective substances]. AB - A case of giant basilar artery aneurysm successfully treated utilizing balloon catheter under the administration of 20% mannitol, dexamethasone, vitamin E (Sendai Cocktail) is reported. The patient, 59 years old female, was admitted to our clinic with complaints of headache. CT scan revealed partially enhanced, round-shaped high density mass with a diameter of 35 mm in the left posterior part of the basal cistern. Vertebral angiography revealed aneurysm at the junction of left posterior cerebral artery and superior cerebellar artery. These findings indicate the partially thrombosed giant basilar artery aneurysm. Direct operation was performed just after the inflation of balloon within the aneurysm which made temporary occlusion of the aneurysm to make the operation safely. After removal of some amount of thrombosed aneurysm, temporary clips were applied on the basilar and bilateral posterior cerebral arteries, and then the neck of aneurysm was clipped. The combined use of the balloon, Sendai cocktail and temporary clips were recommended in such a case. PMID- 3084986 TI - Enzymatic degradation of thyrotropin releasing hormone by pancreatic homogenates. Failure to detect His-Pro-diketopiperazine as TRH metabolite. AB - Characteristics of pancreatic TRH-degrading activity were determined using [L proline-2,3-3H] TRH and [L-histidine-2,5-3H] TRH as tracers and thin-layer chromatography to detect, identify and quantify TRH metabolites following incubation of tritiated TRH with pancreatic homogenates. The apparent Km of pancreatic enzymes was 2.2 10(-5) M, the V, 45 pmol/min, and the apparent specific activity, 62.3 +/- 3.45 pmol/min/mg total protein. In conditions of enzyme saturation, the percent of TRH degraded was found to be similar to the sum of degraded products formed (TRH-OH and His-Pro). Based on the chromatographic identification of metabolites, the presence of a deamidase pathway and a nondeamidase pathway in the TRH-degradation process of the pancreas was postulated. To better characterize the corresponding pancreatic enzymes, active site-directed inhibitors were then used and metabolites yielded were compared to those obtained in the same experimental conditions using plasma as enzyme source. The detection of His-Pro diketopiperazine among the metabolites was of special interest since this biologically active metabolite was also found in the pancreas as an endogenous peptide and reported to be either a TRH degradation product or derived from sources other than just TRH. However, in presence of inhibitors, His Pro diketopiperazine was only detected using plasma as enzyme source. Nevertheless, a pancreatic contribution to plasma TRH-degrading activity cannot be discarded. PMID- 3084987 TI - Effect of abdominal vagotomy at proestrus on ovarian weight, ovarian antral follicles, and serum levels of gonadotropins, estradiol, and testosterone in the rat. AB - The effects of abdominal vagotomy at proestrus on ovarian weight and antral follicles greater than 150 microns diameter and on serum levels of gonadotropins and testosterone were assessed 24 and 48 h and 4 and 8 days after surgery. Serum levels of estradiol were assessed at 4 and 8 days. Vagotomy increased ovarian weight at 48 h, decreased ovarian weight at 4 days, but had no effect by day 8. Vagotomy increased healthy antral follicles 151-394 microns diameter at 24 and 48 h and increased atresia in this size range at 4 and 8 days. Vagotomy decreased healthy follicles 151-384 microns at day 8. Vagotomy decreased healthy follicles 395-570 microns at 24 h and decreased atretic follicles at 48 h. Vagotomy decreased the largest (over 570 micron diameter) healthy follicles at 24 h and 8 days. Vagotomy decreased basal serum LH levels at 48 h and 8 days. (In contrast, vagotomy increased FSH at 24 h). There was no effect on blood levels of estradiol and testosterone. These findings are discussed in relation to the hypothesis that the vagus nerve is a component of the hypothalamo-hypophyseal-ovarian axis. PMID- 3084988 TI - Effects of corticotropin-releasing factor and growth hormone-releasing factor on sleep and activity in rats. AB - The effects of corticotropin-releasing factor (CRF) and growth hormone-releasing factor (GRF) on electroencephalographic (EEG) and behavioral signs of sleep and wakefulness following intracerebroventricular (ICV) administration was investigated in adult male rats. Visual scoring of EEG records as well as spectral analysis revealed that CRF (0.0015-0.015 nmol) produced decreases in slow wave sleep concomitant with significant decreases in spectral power in lower frequencies (1-6 Hz) and increases in high frequencies (32-64 Hz). In contrast, GRF (2.0 nmol) produced increased EEG and behavioral signs of slow wave sleep associated with significant increases in spectral power in the low frequencies (1 2 Hz) and decreases in high frequencies (32-64 Hz). ICV administration of GRF was also found to produce decreases in locomotion when administered during the active part of the rats' circadian cycle. These EEG and behavioral findings seen following CRF and GRF are consistent with the behaviors frequently correlated with the known circadian timing of the release of corticosteroids and growth hormone during the sleep-waking cycle in rat and human. PMID- 3084989 TI - Effects of afternoon injections of melatonin in hypothyroid male Syrian hamsters. AB - Male Syrian hamsters were kept under either 14 h light/10 h dark (lights on at 06.30 h) or 2 h light/22 h dark (lights on at 14.30 h) photoperiods. Groups of hamsters under each photoperiod were rendered hypothyroid by addition of 0.4% thiourea to the drinking water. These hamsters received, in addition, either a daily evening injection of saline or a daily injection of 25 micrograms melatonin in saline. Groups of intact controls and pinealectomized control hamsters were also maintained under the two photoperiodic conditions. After 10 weeks under the different conditions the hamsters were killed by decapitation, and serum samples assayed for thyroxin, thyroid-stimulating hormone (TSH), and prolactin (PRL). Pituitary extracts were assayed for TSH and PRL. Hypothyroidism in hamsters receiving thiourea was confirmed by radio-immunoassay data showing low serum thyroxin and greatly elevated serum TSH concentrations. Melatonin injections resulted in significant depression of serum TSH in thiourea-treated hamsters under short photoperiod compared to saline-injected controls. Both melatonin injections and short photoperiod resulted in a significant reduction of pituitary TSH in hamsters on thiourea compared to values obtained from similarly treated animals under the 14 h light/10 h dark photoperiod. Hypothalamic concentrations of thyrotropin-releasing hormone (TRH) were significantly elevated by melatonin injections and by short photoperiodic conditions, but not by thiourea administration. The short photoperiod resulted in testicular involution which was completely reversed by pinealectomy and partially reversed (to 53% of controls) by thiourea treatment. Involution of gonads was complete in thiourea-treated animals under short photoperiod, if they received melatonin injections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3084990 TI - Effect of plasma from patients containing bupropion and its metabolites on the uptake of norepinephrine. AB - The uptake of norepinephrine into cortical punches from the brain of the rat was studied in the presence of buffer and plasma from patients containing bupropion and its metabolites. Even though bupropion and its metabolite (compound II) were equipotent in inhibiting the uptake of NE in buffer, compound II was twice as active as bupropion in the presence of human plasma. When the inhibition of uptake of NE in the presence of plasma, obtained from patients on bupropion on steady-state, was correlated with levels of bupropion and its metabolites (II, III, IV) a highly significant correlation was seen in the presence of compound II. Since this compound accumulated in plasma from patients 20-100 times that of the parent compound, the mode of action of bupropion may in part be due to the effect of this compound on the uptake of NE. PMID- 3084991 TI - Tremor at rest episodes in unilaterally 6-OHDA-induced substantia nigra lesioned rats: EEG-EMG and behavior. AB - Twenty male adult Wistar rats were unilaterally lesioned in the substantia nigra (SN) with 6-hydroxydopamine (6-OHDA), and prepared with chronic cortical (ECoG) and neck muscle (EMG) electrodes. Longitudinal study over a period of up to 18 months demonstrated the emergence, in about two-thirds of the rats, of spontaneous repetitive episodes of head and neck tremor during awake at rest, of up to 20 seconds duration each, that were associated with spike and wave-like ECoG activities. These episodes of tremor at rest disappeared during sleep and REM sleep episodes, and also following the i.p. administration of L-DOPA. It is assumed that these tremor at rest episodes are analogous to those reported to occur in primates after experimentally induced dysfunction of the nigro-striatal, extrapyramidal system. PMID- 3084992 TI - Serine-O-phosphate, an endogenous metabolite, inhibits the stimulation of inositol phospholipid hydrolysis elicited by ibotenic acid in rat hippocampal slices. AB - Serine-O-phosphate (PS) inhibits the accumulation of 3H-inositolmonophosphate elicited by ibotenic acid in rat hippocampal slices incubated in the presence of 7 mM Li+. This inhibition is concentration- dependent and stereoselective, L-PS being 5 fold more potent than D-PS. Among different structural analogues of PS, only L-serine weakly antagonizes the action of ibotenic acid, whereas phosphorylcholine, phosphorylethanolamine and phosphothreonine are inactive even at high concentrations. These results are consistent with the hypothesis that L PS may act as an endogenous regulator of excitatory amino acid receptor function. PMID- 3084993 TI - Surgonomics: the cost dynamics of craniotomy. AB - Prospective payment systems using the diagnostic related group (DRG) mechanism are being phased in for Medicare inpatient hospital care. The purpose of this study was to examine a common neurosurgical procedure (001), craniotomy without trauma, and characterize the cost dynamics of this DRG. All patients (n = 50) treated in this DRG at the Long Island Jewish Medical Center during 1983 had their financial charges exclusive of physician fees examined. The findings were: (a) each hospital service category had wide charge variances around the mean; (b) emergency (ER) admissions were 200% more expensive than nonemergency (non-ER) admissions; (c) ER admissions seemed to have no greater severity of illness than non-ER admissions, but had a significantly different referral pattern (i.e., admission from the ER to a nonneurosurgical service with a subsequent neurosurgical referral); (d) this DRG when grouped into clinical "subproducts" (i.e., craniotomy for tumor, hematoma, hydrocephalus, aneurysm, benign cyst, and other) showed marked charge differences; and (e) the most expensive 25% of patients had five times higher charges than the least expensive 25% for both ER and non-ER admissions. This type of financial analysis may give surgeons a methodology with which to address the problems of cost containment in a more serious manner. PMID- 3084995 TI - Neuroimaging in refractory partial seizures: comparison of PET, CT, and MRI. AB - We compared the results of x-ray CT, magnetic resonance imaging (MRI), and positron emission tomography (PET) using 18F 2-deoxyglucose in 36 patients with partial seizures. Seventeen patients had localized epileptic discharges on surface EEG. MRI showed an abnormality in 9, CT in 4, and PET in 13 of 14 patients who had the test. Nineteen patients had nonlocalizing EEG discharges. MRI showed an abnormality in 11, CT in 10, and PET in 8 of 12. MRI is more sensitive than CT in detecting structural lesions underlying PET hypometabolism. PMID- 3084994 TI - Spinal neurofibromas: a report of 66 cases and a comparison with meningiomas. AB - A series of 66 spinal cord neurofibromas was analyzed for history, signs, surgical approach, and outcome. The tumors presented primarily with sensory symptoms. Plain films were abnormal in 1/2 of cases and 1/2 had a complete block. They were primarily intradural, and primarily thoracic. A conservative exam system was used for follow-up and 85% with pain had complete relief; 50% with motor loss had normal motor function, and 88% had normal sensation who had prior sensory loss. In comparison to meningiomas, the principal differences were that neurofibromas had an even sex distribution, a lower incidence of cord signs and symptoms, more frequent findings on plain x-rays, and higher cerebrospinal fluid protein. Surgical outcome was similar. Sacrifice of the involved root during removal usually did not produce a deficit. The series is compared with a similar series of meningiomas from the same institution over the same time period. PMID- 3084996 TI - Juvenile-onset acid maltase deficiency with unusual familial features. AB - From early childhood, two brothers had mild gait difficulties due to acid maltase deficiency (AMD). Biochemical studies of family members were consistent with autosomal recessive inheritance, but the asymptomatic mother had AM activity in the homozygote range, and her parents had decreased AM activity. The asymptomatic mother may be homozygous for the adult-onset variant of AMD. Alternatively, either the mother or the children may be genetic compounds of the childhood and adult forms of AMD. PMID- 3084997 TI - Short-duration airblast exposure does not increase pulmonary microvascular permeability. PMID- 3084998 TI - Emergency evacuation of the Denver Veteran's Administration Medical Center. PMID- 3084999 TI - The psychological symptomatology of a U.S. Naval disaster. PMID- 3085000 TI - Spinal cord decompression sickness after standard U.S. Navy air decompression. PMID- 3085001 TI - Hyperthyroidism following surgical stress in previously euthyroid patients. PMID- 3085002 TI - Marital adjustment and personality in aviation-rated and nonrated warrant officers. PMID- 3085003 TI - Neonatal tetanus: a case report and review of modern therapy. PMID- 3085004 TI - Endoscopic removal of a foreign body from the tracheobronchial tree: a new technique. PMID- 3085005 TI - Torsed infected dermoid cyst with concurrent ectopic pregnancy. PMID- 3085006 TI - Sedation for pediatric procedures. PMID- 3085007 TI - An evaluation of the weight control program at a U.S. Army installation. PMID- 3085008 TI - Childhood heart murmur. PMID- 3085009 TI - The test of a computerized outpatient recording/reporting system for Army troop medical clinics. PMID- 3085010 TI - The effects of withdrawal methods on arterial cannula dysfunction. PMID- 3085011 TI - Medical advice for foreign travel. PMID- 3085012 TI - Bladder rupture associated with fractured pelvis in blunt trauma to the abdomen. PMID- 3085014 TI - Pilot study: a digital toothbrushing technique for field use. PMID- 3085013 TI - Vascular graft coverage in peripheral vascular injuries. PMID- 3085015 TI - Administrative error: false imprisonment. PMID- 3085016 TI - [Complicated jejunal diverticulosis: a rare cause of surgical acute abdomen]. PMID- 3085017 TI - [Total parenteral nutrition in cancer patients in intermediate and terminal stages]. PMID- 3085018 TI - [Parenteral amino acid integration in chronic hepatic encephalopathy in oral low protein treatment]. PMID- 3085019 TI - [Anastomotic dehiscence and conservative therapy. Technical note]. PMID- 3085020 TI - [The role of total parenteral nutrition in the treatment of acute stage surgical colonopathies]. PMID- 3085021 TI - [Acromegaly. Physiopathological aspects and description of a clinical case]. AB - Recent physiopathological studies suggest that hypersecretion of GH in acromegaly is not necessarily the result of a primary alteration to the GH-secreting pituitary cells. Some suggest that an alteration in the hypothalamic control of the hormone secretion may also be involved. After a general introduction, a clinical case of acromegaly is reported. PMID- 3085022 TI - [Duodenal diverticula]. PMID- 3085023 TI - [Endoluminal diverticulum of the duodenum. Report of 2 cases]. PMID- 3085024 TI - [Number, site and size of duodenal diverticula and the associated clinical picture in 78 patients with duodenal diverticulosis]. PMID- 3085025 TI - [Possible correlations between diverticula of the 2d portion of the duodenum and pancreatic pathology]. PMID- 3085026 TI - [Duodenal diverticula]. AB - After an examination of the anatomopathological and clinical features of duodenal diverticula, the various ancillary pathologies are analysed as are the complications linked to the diverticulum itself. A meticulous review of the literature and several personal surgical cases confirms the view that only those diverticula causing evident symptoms or complications should be treated. The various surgical techniques selected as appropriate for the different cases are also described. PMID- 3085027 TI - [Plasmapheresis in Rh isoimmunization. Monitoring various parameters of blood crasis and coagulation]. PMID- 3085028 TI - Establishing a nutritional support team in a rural hospital. PMID- 3085029 TI - Specialized nutrition support in New Jersey under the prospective payment system. PMID- 3085030 TI - Withholding nutrition: a nursing perspective. PMID- 3085031 TI - Rationing of health care: the inevitable meets the unthinkable. PMID- 3085032 TI - Appendiceal diverticulum: an unusual but not uncommon entity. PMID- 3085033 TI - [Radiological study of the vascularization of DMBA-induced tongue cancers in hamsters]. PMID- 3085034 TI - No free lunch. PMID- 3085035 TI - [Use of lysine acetylsalicylate in correcting hemodynamic disorders in ocular contusion in an experiment]. PMID- 3085036 TI - Inhibition of the binding of 7,12-dimethylbenz[a]anthracene to DNA by ascorbic acid, reduced glutathione and cysteine in chick embryo cells cultured in vitro. AB - A study on the capacity of ascorbic acid, reduced glutathione and cysteine to interfere with 3H-7,12-dimethylbenz[a]anthracene (3H-DMBA) binding to DNA in cultured fibroblast-like cells from 11-day-old chick embryos showed that, although the total amount of 3H-DMBA in the treated cells was greater than in the untreated cells, the DNA-bound 3H-DMBA was less. Comparisons between the various experimental groups demonstrated that the greater 3H-DMBA in the ascorbic acid-, reduced glutathione-, and cysteine-treated groups could not be attributed to an initially higher number of cells, nor to a treatment-induced increase in DNA synthesis. It is proposed that the three substances examined inhibit the oxidative degradation of 3H-DMBA, thereby favoring its accumulation within the cell and reducing the formation of DNA-binding metabolites. PMID- 3085037 TI - Intraocular and extraocular colobomatous cysts in adults. AB - A 29-year-old woman had a colobomatous multiloculated cystic left eyeball. None of the normal structures of the globe were discernable by clinical examination. The cyst had been present since birth and had not grown in size since early childhood. Another patient, a man of 73, had an intraocular colobomatous cyst occupying the temporal half of the large choroidal bridge coloboma in his left eye. This cyst was partially filled with shimmering crystalline fluid. This patient had bilateral open-angle glaucoma which had caused advanced damage to the optic nerve in the structurally normal right eye. It is interesting that glaucoma did not affect the left eye with choroidal coloboma and intraocular colobomatous cyst, which had normal vision. The author thinks that ectatic sclera in the area of coloboma might have protected the eye from elevated intraocular pressure. PMID- 3085040 TI - Integrating quality assurance, utilization review, and risk management activities for the small hospital. PMID- 3085039 TI - Preventing malpractice suits in long term care facilities. PMID- 3085038 TI - Photosensitizing drugs and their possible role in enhancing ocular toxicity. Parker Heath memorial lecture. AB - During the past decade there has been a considerable resurgence of interest in the photochemical effects of ultraviolet radiation capable of penetrating through the cornea (300-400 nm), on the intraocular tissues. The ocular lens and retina have received the most attention. The last few decades have also witnessed the development of a new therapeutic regimen, namely photosensitizing (phototherapy), in which the patients are given known photosensitizing agents and exposed to nonionizing radiation (ultraviolet, and on occasion, visible radiation). Such therapy has caused some ocular side effects, which in most cases could have been prevented. Drugs that are known photosensitizers and are capable of intraocular penetration through the blood-aqueous and blood-retina barrier are discussed with respect to their known or potential photosensitizing and/or phototoxic effects on intraocular tissues. PMID- 3085041 TI - A 12-year audit of IRB decisions. AB - Institutional review boards (IRBs) are inter-disciplinary committees mandated by the federal government to review all research protocols that involve human subjects developed in institutions receiving federal funds. The purpose of the IRB is to protect those subjects from unnecessary risk or from risks that outweigh potential benefits. At Boston City Hospital, a study was conducted of the decision-making process of the hospital's IRB over a 12-year period (from 1973-1984) to determine empirically the types of research protocols reviewed, problems frequently addressed, actions taken, and the consistency of the decision making process. PMID- 3085042 TI - The QIP form: the one-page quality assurance tool. AB - Recognition of the need to document and track corrective action plans led to the development in 1980 of the quality improvement plan (QIP). The QIP form includes ten categories such as quality assurance (QA) assessment and initiator's recommendation; it helps provide information for the hospital QA committee and the QA program. The QIP form has helped identify 50 current QA concerns at the Methodist Hospital of Indiana, Inc., in Indianapolis indicating its successful implementation. PMID- 3085043 TI - Incident reporting: evaluation of New York's pilot incident logging system. AB - A revised incident reporting system that combined an abbreviated logging procedure for documenting minor incidents and a more comprehensive and detailed procedure for documenting major incidents was pilot tested in three New York State adult psychiatric centers. The pilot test had two major goals: to reduce the volume of work associated with current reporting procedures, and to facilitate even more thorough investigation of incidents warranting prompt and comprehensive review. Evaluation of pilot study data showed that a logging procedure is viable for the management of minor incidents. PMID- 3085044 TI - Criteria and standards for quality assessment and monitoring. PMID- 3085045 TI - [Diagnostic value of disaccharide action in diseases of the small intestine in childhood]. PMID- 3085046 TI - [A case of generalized tissue resistance to thyroid hormones]. PMID- 3085047 TI - [Hyperoxia-hyperventilation test in the diagnosis and therapy of persistent neonatal pulmonary hypertension]. PMID- 3085048 TI - [Clarification of causes of post-pill amenorrhea]. PMID- 3085049 TI - [Future ways of hospital financing and their effects on hospital organization]. PMID- 3085050 TI - Annual meeting of the American Academy of Otolaryngology--Head and Neck Surgery Foundation, Inc. San Antonio, Texas, September 14-18, 1986. 1986 instruction course program. PMID- 3085051 TI - Quality of care--physician's beacon. PMID- 3085052 TI - Genetic control of immunity to Trichinella spiralis in mice. Response of rapid- and slow-responder strains to immunization with parasite antigens. AB - Slow-responder C57BL/10 (B10) mice responded poorly to immunization with muscle larval antigen of Trichinella spiralis showing no accelerated loss of worms from a subsequent challenge infection. In contrast, rapid-responder NIH mice and (B10 X NIH) F1 mice developed high levels of immunity after immunization. Lymphocyte proliferation studies showed that immunized B10 mice did respond to in vitro restimulation with antigen, though less well than NIH mice. Failure of B10 mice to respond to immunization did not therefore reflect a failure to recognize larval antigen, a view confirmed by the fact that immunization was achieved using abbreviated enteral infections and, to a smaller extent, by parenterally administered muscle larvae. PMID- 3085053 TI - Bovine T-cell clones infected with Theileria parva produce a factor with IL 2 like activity. PMID- 3085054 TI - The identification of Schistosoma mansoni surface antigens recognized by protective monoclonal antibodies. PMID- 3085055 TI - [Effect of polyene antibiotics on prostaglandin synthesis in various layers of the kidneys in old rats]. PMID- 3085056 TI - Ultrasonographical aspects of urinary schistosomiasis: assessment of morphological lesions in the upper and lower urinary tract. AB - Ultrasonographic evaluation of 213 patients with urinary schistosomiasis in different age groups was performed in an endemic area of the Democratic Republic of Congo. The results were compared with 94 age matched controls without urinary schistosomiasis. In patients the bladder showed thickening of the wall, polypoid lesions of the mucosa and bladder wall, calcifications and urinary retention. Urinary tract obstruction, predominantly unilateral, was demonstrated. The lesions increased in severity with the intensity of infection, parallel to an increase in ova excretion. Children aged between 8 and 19 years were most severely affected. Pathological lesions of the upper urinary tract were rare in patients over 25 years of age. The combination of morphological abnormalities was interpreted as being specific for urinary schistosomiasis as they did not occur in the control group. It is suggested that real time ultrasonography may be used to identify morphological lesions in urinary schistosomiasis. PMID- 3085058 TI - Controlled hypercapnia and neonatal cerebral artery Doppler ultrasound waveforms. AB - Eleven normal term infants undergoing respiratory assessment involving rebreathing to produce progressive hypercapnia were studied by Doppler ultrasound examination of an anterior cerebral artery during the procedure. A linear increase in end tidal carbon dioxide concentration from 4.5% to a maximum of 8.5% was documented during a period of 4-5 min rebreathing. A corresponding elevation of transcutaneous carbon dioxide tension was shown in the two infants monitored in this way. In all cases the Pourcelot index fell with rising end tidal carbon dioxide concentration. This fall in Pourcelot index was due to an increase in the diastolic frequency of the Doppler waveform. These results are consistent with the view that Pourcelot index correlates with cerebral vascular resistance distal to the site of recording. PMID- 3085057 TI - A case of a thoracic vertebral body dislocation without neurological signs in a child with neurofibromatosis. AB - In a 10-year-old child with neurofibromatosis, dislocation of a thoracic vertebral body was noted almost by accident; a singular dislocation unaccompanied by neurological symptoms. PMID- 3085059 TI - Involvement of developing sympathetic nervous system in thyroxine-mediated submandibular gland nerve growth factor and epidermal growth factor responses. AB - Thyroxine (T4) administration in mice during the 2nd wk of postnatal life elicits a precocious increase in submandibular gland-nerve growth factor (SMG-NGF) and epidermal growth factor (SMG-EGF) levels, but the mechanism(s) of T4 action has not been studied. The present report examines the role of the developing sympathetic nervous system (SNS) in the SMG-NGF and EGF responses to T4. For this purpose newborn mice were injected with T4 and/or 6-hydroxydopamine, a toxic congener of norephinephrine which causes selective destruction of sympathetic nerve terminals. The effectiveness of chemical sympathectomy was assessed by SMG norepinephrine measurements using a sensitive radioenzymatic assay. The glandular norepinephrine contents were greatly reduced indicating that the dose and duration of 6-OHDA treatment were sufficient to cause a total sympathectomy in SMG tissue. In addition, the 6-OHDA treatment greatly reduced the wet weight and total protein content of the sympathetic superior cervical ganglia which innervate SMG tissue. SMG-NGF and EGF concentrations were measured by specific radioimmunoassays. 6-OHDA treatment alone did not affect the basal SMG-NGF and EGF concentrations. However, the maximal responses of SMG-NGF and EGF to T4 administration were greatly reduced by concurrent treatment with 6-OHDA. In summary, the data demonstrate a critical role for developing sympathetic nervous system in the T4-stimulated increase in SMG-NGF and EGF concentrations. PMID- 3085060 TI - Biochemical and histologic pathology in an infant with cross-reacting material (negative) pyruvate carboxylase deficiency. AB - An infant with the acute neonatal form of pyruvate carboxylase deficiency (cross reacting material negative) presented with severe intractable lactic acidosis within 4 h after birth. He also had hyperammonemia, hypercitrullinemia, and hyperlysinemia. Plasma glutamine was not elevated. He had a rapidly deteriorating clinical course with severe liver dysfunction, repeated septicemia and seizures; he was comatose and was on a ventilator throughout; death occurred at 8 wk of age. Skin fibroblast study confirmed the enzyme deficiency. Detailed biochemical parameters and histopathology of the brain and liver are presented. The evidence from this infant suggests that disturbances of intracellular oxaloacetate levels as a result of the primary enzyme defect might also contribute to deficiency in ATP generation which may explain the various other biochemical changes and liver pathology. PMID- 3085062 TI - Impact of selected diagnosis-related groups on regional neonatal care. AB - The evaluation and reimbursement of hospital use by means of diagnosis-related groups (DRGs) may have a major impact on the utilization of regional neonatal care. Medicare has already implemented the DRG system and other payors, including Medicaid, Blue Cross, and commercial insurance, are also considering adopting it. Under this approach, neonates are assigned to one of seven DRGs, each of which is reimbursed at a relatively fixed rate. An evaluation of hospital utilization by neonates focused on three of these DRGs in four regional neonatal systems located in Upstate New York. Calendar year 1983 data indicated that Level III, II, and I neonatal facilities generated substantially different mean stays for these DRGs in the four regions. The ranges of mean stays between Level III and Level I facilities were greatest for DRGs involving neonates who died or were transferred and those with extreme immaturity and/or respiratory distress syndrome. Federal length of stay and cost standards for these categories failed to address the different utilization experience of these levels of care. The analysis suggests that, as additional payors adopt DRGs, the standards relating to neonatal care must be modified. PMID- 3085061 TI - Apolipoprotein and lipid composition of plasma lipoproteins in neonates during the first month of life. AB - In this study the lipid and apoprotein profiles were investigated in newborns at 0, 7, and 30 days of life. The plasma lipoproteins were separated both by ultracentrifugation and gel filtration in order to compare the patterns obtained by the two techniques. At birth, the apo E concentration is comparable to that measured in adults, but its distribution among lipoproteins is significantly different as more than 80% of the plasma apo E belongs to high-density lipoproteins (HDL). At 7 and 30 days the plasma apo E concentrations are close to the values at birth, but a significant redistribution occurs from HDL to very low density lipoproteins. By analogy with apo B, the plasma apo CIII concentration is low at birth and increases between 0 and 7 days by a factor of about two. Plasma triglycerides increase significantly during the first week of life so that the apo CIII increase is most pronounced in very low-density lipoproteins. These lipoproteins therefore become enriched in apo E, apo CIII and triglycerides between 0 and 7 days. At birth, a distinct HDL fraction, enriched in apo E, apo AII and cholesterol (HDLE), could be detected. To compensate for the low LDL levels, this HDLE fraction might function as an additional source for cholesterol delivery to peripheral tissues via the apo (B, E) receptor. At later age, low density lipoprotein synthesis is enhanced, apo E is transferred to very low density lipoproteins, and cholesterol delivery via the HDLE becomes less important.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085063 TI - Acquired arteriovenous fistulas of the scalp in hemophiliacs. AB - The development of arteriovenous fistulas following multiple intravenous infusions in hemophiliacs has been previously reported. In this report, we discuss two patients in whom arteriovenous fistulas developed following the use of scalp veins as sites of infusion. Because of the rich vascularity of this area and the proximity of the arterial and venous systems we recommend that this site not be used for factor infusion. PMID- 3085064 TI - Partial seizures in children. AB - Although partial seizures occur frequently in childhood, the clinical and EEG manifestations have not been well described. Clinical and EEG features of 198 partial seizures in 56 children with seizures recorded during videotape monitoring with simultaneous telemetered EEG recordings were analyzed. Simple partial seizures were short in duration and consisted primarily of motor symptoms and were not associated with postictal impairment. Complex partial seizures were longer and could be categorized into four subgroups based on the initial clinical manifestations: staring, automatisms, motor phenomena, and drop attacks. All complex partial seizures were associated with changes in facial expressions, and in 87% of the patients automatic behaviors occurred either initially or at some point during the seizures. Unlike simple partial seizures, complex partial seizures were often associated with postictal symptoms. Although complex partial seizures were variable in manifestations from patient to patient, in children with more than one seizure recorded clinical events were usually stereotyped. PMID- 3085065 TI - Computed axial tomographic scanning of the thigh: an alternative method of nutritional assessment in pediatrics. AB - In this study we compared the findings of computed axial tomographic (CT) scanning of the thigh with the findings of arm anthropometry and urinary creatinine determinations to assess nutrition in children with inflammatory bowel disease receiving total parenteral nutrition. All 14 children received our standard solution for total parenteral nutrition as well as prednisone and sulfasalazine (Azulfidine) therapy. All patients were assessed by arm anthropometry, 24-hour urine collections for creatinine clearance, and CT scanning of the thigh during total parenteral nutrition. Arm muscle and fat area were estimated by anthropometry, and those in the thigh were estimated by CT scanning. Our results show the total muscle area from the CT scan can predict muscle mass calculated from the urinary creatinine excretion rates. In addition, there is a close correlation between the thigh muscle area as measured by CT scanning and the muscle area calculated from urinary creatinine excretion rates. In addition, the comparison of thigh muscle area and thigh fat area to the midarm muscle area and midarm fat area, respectively, showed that the thigh is a better predictor of muscle than fat in the midarm. We conclude that the total thigh muscle area is a better predictor of muscle mass as compared to the midarm muscle area. In addition, the CT scan cut at the level of the thigh in children and adolescents with inflammatory bowel disease can provide valuable information about the thigh compartment and analyses of different cross-sectional areas of the thigh. PMID- 3085066 TI - Psychosocial issues in pediatric organ transplantation: the parents' perspective. AB - The process of organ transplantation for a child has a profound impact on the entire family. Parents are faced with a number of psychosocial stresses many of which are unique in a pediatric hospital setting. We report the information provided by parents who have participated in a support group established for those with children undergoing heart and liver transplantation. Descriptive information gathered throughout the past 4 years in this group suggests that there are three specific stages that these families must endure: preoperative, perioperative, and long-term postoperative. The major psychosocial obstacles for families at each stage of the transplant process are described in detail. This information provides the health care professional with a basic framework to understand and provide guidance to the families of transplant patients. PMID- 3085067 TI - Monitoring patients in pediatric intensive care. PMID- 3085069 TI - Caring for older people: a challenge for nurse administrators. AB - The findings of this exploratory study emphasize the importance of communication between and among nurse administrators in various settings for patient education, staff development and coordination of services to provide continuity of care for older people. The nurse administrator in all settings is in a key position to seek internal and external funding for creative programs and establishing standards for care. This study has merely tapped the surface; much more research needs to be carried out, especially in nursing homes, to understand the complex health problems of older people. PMID- 3085068 TI - Compilation of small ribosomal subunit RNA sequences. PMID- 3085070 TI - Management: a perfect match? PMID- 3085071 TI - The challenge of the nursing role in the rehabilitation of the elderly stroke patient. AB - Health professionals often share in the public's patronizing attitude toward a stroke patient. Since the stroke patient is often an older adult, that discriminatory attitude is reinforced by the stereotypes and myths about aging. Hence, the role of the nurse in rehabilitation of an elderly stroke patient calls for a sophisticated understanding of the situation. Not only should the patient's mental, social, and personal needs be taken into account, but also the difficulties that stem from the structure and culture of an acute-care hospital and the peculiar circumstances of the caregiver at home. We have recorded significant gains regarding strokes on the clinical front. The next challenge is to achieve success in the careful management and rehabilitation of the elderly stroke patient. The nurse can lead the way. PMID- 3085072 TI - Dietary vitamin A and cancer--a multisite case-control study. AB - The relationship between an index of dietary vitamin A and cancer risk at 25 sites was assessed in retrospective case-control studies. Common control groups for males and females were used in all analyses. Relative risk estimates were derived from multiple logistic regression analyses that controlled for age, alcohol consumption, and smoking exposure. We found that among males, dietary vitamin A is associated with lower risk for cancers of the tongue, floor and other mouth, pharynx, larynx, esophagus, and lung but higher risk for Hodgkin's disease and leukemia. Among females, we found that dietary vitamin A had less effect on risk generally but was associated with lower risk for bladder cancer. These findings are consistent with previous research that showed dietary vitamin A to be associated with decreased risk of squamous epithelial cancers. The association of dietary vitamin A and increased risk of Hodgkin's disease and leukemia among males in addition to the disparity in effect of dietary vitamin A on risk between males and females are areas worthy of further research. PMID- 3085073 TI - Trypsin inhibitor ingestion-induced urinary indican excretion and pancreatic acinar cell hypertrophy. AB - Sodium saccharin (NaSacc) has been shown to be a protease inhibitor and to induce an increase in urinary indican, which is a product that is dependent on microbial metabolism of tryptophan. These findings suggest that urinary indican might provide a noninvasive marker of increased pancreatic acinar cell size associated with plant trypsin inhibitor ingestion. The results demonstrate the 7.5% of dietary NaSacc, which increases urinary indican, also increases relative pancreas mass (g/kg body weight), and that these effects are not induced by intravenous infusion of NaSacc. Dietary soybean trypsin inhibitor in the dose range of 17-713 mg/100 g diet was associated with parallel dose-dependent increases in urinary indican and pancreatic acinar cell size (assessed histologically). These findings suggest that measurement of relative urinary indican excretion (microgram/g diet ingested) can provide a noninvasive marker of increased pancreatic acinar cell size in rats that ingest compounds which inhibit digestive proteases. PMID- 3085074 TI - [Histocompatibility antigens (HLA) in mental disorders]. PMID- 3085075 TI - Stepwise evaluation of the short child. With comments on the status of growth hormone therapy. AB - The role of the primary care physician in evaluating short children is to select those children with true growth failure by careful documentation of height measurements. A directed history and physical examination and limited laboratory testing should identify children with nutritional, structural, or inflammatory causes of poor growth and suggest specific therapy. In those few children with growth hormone deficiency, more complicated and expensive testing and therapy are necessary. PMID- 3085076 TI - Adult hypothyroidism. 2. Causes, laboratory diagnosis, and treatment. AB - Hypothyroidism may be self-limiting or may progress to thyroid failure, depending on the cause. Thus, diagnosis of the underlying disorder is extremely important. Once the diagnosis is established, the origin and cause of hypothyroidism must be identified. A careful history and physical examination, routine laboratory tests, and demonstration of antithyroid antibodies will ordinarily lead to the correct diagnosis. Self-limited disorders require little or no therapy. Progressive disease is treated with a thyroid hormone preparation. Myxedema coma is an endocrine emergency that requires prompt treatment of both the metabolic complications and any intercurrent illness. PMID- 3085077 TI - Hypothyroidism with angina pectoris. A clinical dilemma. AB - Management of patients with chest pain and hypothyroidism is a clinical dilemma. Thyroid replacement therapy may exacerbate angina pectoris. Administration of a beta blocker such as propranolol (Inderal) concomitantly with thyroid replacement therapy is useful in treatment of angina. However, beta blockers can induce variant angina owing to increased norepinephrine secretion and enhanced alpha mediated responsiveness in the hypothyroid state. Hypotension and syncopal episodes may develop in the hypothyroid patient after administration of nitrates. Cardiac catheterization and revascularization are well tolerated by myxedematous patients with angina. After surgery, full thyroid replacement therapy should be initiated gradually and with caution. PMID- 3085078 TI - Influence of virginiamycin and dietary manganese on performance, manganese utilization, and intestinal tract weight of broilers. AB - An experiment was conducted with day-old Cobb feather-sexed chicks for 21 days to study the effect of virginiamycin and dietary manganese on tissue uptake of manganese and intestinal tract weight. The 2 X 2 factorial arrangement of dietary treatments included 0 or 12 ppm virginiamycin and 0 or 1000 ppm added manganese as MnSO4 X H2O. Ad libitum intake was determined with four pens of five birds fed the basal corn-soybean meal diet. To eliminate the possibility that tissue manganese concentration of virginiamycin-fed birds could be attributed to increased dietary manganese intake, chicks fed experimental diets were restricted to 90% of the previous day's intake of ad libitum-fed birds. Feed intake, average daily gain, and feed efficiency were not affected by treatments. Virginiamycin decreased (P less than .001) relative intestinal tract weight from 3.34 to 2.68 g/100 g body weight. Kidney and bone manganese increased (P less than .05) when virginiamycin was fed (14.0 vs. 15.4 ppm dry basis and 21.8 vs. 24.6 ppm ash basis, respectively), indicating that virginiamycin increased absorption of manganese. PMID- 3085079 TI - Effect of thyroid hormones on growth hormone secretion in broiler chickens. AB - Plasma concentrations of growth hormone (GH) were observed to be significantly elevated following the administration of thyrotropin-releasing hormone (TRH) in young (4- to 12-week-old) but not in adult (20-week-old) broiler chickens. However, adult sex-linked (dw) dwarf hens did respond to TRH. Treatment with triiodothyronine (T3) but not thyroxine (T4) (at 1 ppm in the diet from hatch) consistently and significantly reduced the growth rate and decreased the plasma concentrations of GH following TRH injection in normal (DwDw males or Dw females), hemizygous dwarf (dw-) female, and heterozygous (Dwdw) male lines of broiler chickens. Similarly, T3 was significantly more effective than T4 in inhibiting the increase in plasma concentrations of GH following TRH injection in broiler chicks made hypothyroid by methimazole administration. PMID- 3085080 TI - Effects of hot environments and carbonated drinking water on bone characteristics of eight-week-old broiler chicks. AB - Epiphyses of the femura from 8-week-old broiler chicks were examined for morphology using scanning electron microscopy and for elemental composition using energy dispersive x-ray microanalysis. Birds between the ages of 4 and 8 weeks were subjected to either 25 or 35 C environments and given tap or carbonated drinking water. The morphological appearance of the epiphyses was affected by the kind of drinking water but not the thermal environment. Elemental constituents, however, were affected by both environmental temperature and drinking water. PMID- 3085081 TI - Does or can human placenta produce prostacyclin? AB - In order to resolve contradictory data on the capacity of the human placenta to produce prostacyclin (PGI2), we have quantified PGI2 synthase in 12 placentae obtained in the first trimester of pregnancy. Using a specific immunoradiometric assay and two monoclonal antibodies against the enzyme, we found PGI2 synthase to be present in the microsomal fraction of all placentae investigated, albeit in concentrations that were 1000-fold lower than in bovine aortal microsomes and 100 fold lower than in both pregnant and non-pregnant myometrium. Comparison of these data with previous reports on placental PGI2 production suggests that the contradictions between previous data are more apparent than real. We conclude that the human placenta possesses the potential for PGI2 production, that it therefore 'can' produce PGI2, but that it remains uncertain whether the placenta actually 'does' or 'does not' produce PGI2 in vivo. PMID- 3085082 TI - Calcium-activated neutral protease from human placenta: purification and characterization. AB - Calcium-activated neutral protease (CANP) has been purified from the human placenta by chromatographic procedures. The purified enzyme is a heterodimer with one subunit of mol. wt 70 000 and another of mol.wt 32 000. It is a thiol protease, active at pH 7.5 at 30 degrees C in the presence of calcium. Half maximal activation of the enzyme occurred with 800 microM Ca2+.Zn2+ (2 mM), ethylenediaminetetraacetic acid (EDTA)(5 mM) and ethyleneglycol-bis-N,N,N',N' tetraacetic acid (EGTA)(2 mM) inhibited the enzyme, while Mg2+ (0.5 mM to 5 mM) had no effect on the enzyme in the presence of calcium. Mn2+ and Ca2+ activated the enzyme synergistically. CANP coexists with its endogenous inhibitor in the human placenta. The inhibitor is a protein, inactivated by trypsin and unaffected by RNase, DNase, acid and heat treatments; it inhibits the enzyme probably by interacting with the enzyme molecule itself rather than by sequestering calcium ions. PMID- 3085083 TI - The epilepsy of Dostoevsky. AB - The evidence in favour of a diagnosis of limbic epilepsy in the case of Dostoevsky is reviewed. Independent records from numerous biographical sources support the widely held view that Dostoevsky had frequent convulsive episodes, that the episodes began in childhood and continued throughout his life and that Dostoevsky himself was able accurately to record the premonitory aura and sequelae of such episodes. In addition the increasing memory impairment he suffered both for recent and remote events from the age of 40 supports the presence of progressive brain damage. This information renders implausible the analytic interpretations of Freud and his followers, that Dostoevsky's epilepsy was hysterical in origin, where epileptiform somatization was presumed to dispose of excessive psychic excitation, and that this process had its roots in Dostoevsky's unconscious hatred of his father and latent homosexuality. Nevertheless, Dostoevsky's neuroticism is clearly supported by his life-long hypochondriasis, obsessionality, paranoid traits, tendency to reactive depressions, and experience of quasi-hallucinatory episodes which were probably not epileptic in origin. Neither his epilepsy nor his neuroticism can explain or detract from the profundity and wisdom of the literary monuments which clearly attest Dostoevsky's ample genius. PMID- 3085084 TI - Biphasic effects of estrogen on apolipoprotein synthesis in human hepatoma cells: mechanism of antagonism by testosterone. AB - Treatment of HepG2 cells with various concentrations of 17 beta-estradiol has revealed two distinct thresholds for induction of different apolipoproteins. Maximal increases in apolipoprotein AI and CII (apoAI and apoCII) secretion can be obtained with initial concentrations of hormone of 20 nM or greater, while a similar induction of apoB and apoE requires in excess of 500 nM. Both responses involve alterations in the concentrations of apolipoprotein mRNAs. Analyses of the kinetics of accumulation of the apolipoproteins in response to high concentrations of hormone indicate that induction of apoB and apoE occurs coordinately, but it lags behind that of apoAI and apoCII by 5-6 hr. This lag can be eliminated by preexposing the cells to low concentrations of hormone. The ability to induce apoAI and apoCII and the kinetics with which they respond to low levels of estrogen correlate with levels of nuclear type I estrogen binding sites, while increases in apoE and apoB synthesis in response to high concentrations of hormone correlate with the induction of type II sites. Testosterone alone has no effect on the rates of apolipoprotein secretion, but it does increase the concentration of estrogen required to maximally induce apoCII and apoAI by a mechanism that involves high-affinity androgen receptors. This effect may be attributable to the testosterone-dependent induction of a cytoplasmic moderate-affinity estrogen-binding component. PMID- 3085085 TI - Identification of a positive retroregulator that stabilizes mRNAs in bacteria. AB - A positive retroregulator that enhances the expression of an upstream gene(s) has been identified. It resides within a 381-base pair (bp) restriction fragment containing the transcriptional terminator of the crystal protein (cry) gene from Bacillus thuringiensis vs. Kurstaki HD-1. This fragment was fused to the distal ends of either the penicillinase (penP) gene of Bacillus licheniformis or the interleukin 2 cDNA from the human Jurkat cell line. In both cases, the half-lives of the mRNAs derived from the fusion genes were increased from approximately equal to 2 to 6 min in both Escherichia coli and Bacillus subtilis. Synthesis of the corresponding polypeptides in the bacteria carrying the fusion genes was also increased correspondingly. The enhancement of expression of the upstream genes was independent of the insertional orientation of the distal cry terminator fragment. Deletion analysis showed that the locus conferring the enhancing activity coincided with the terminator sequence and was located within a 89-bp fragment that includes an inverted repeat, the 19-bp upstream-, and the 27-bp downstream-flanking sequences. We propose that transcription of the retroregulator sequence leads to the incorporation of the corresponding stem-and loop structure at the 3' end of the mRNA; the presence of this structure protects the mRNAs from exonucleolytic degradation from the 3' end and, thereby, increases the mRNA half-life and enhances protein synthesis of the target genes. PMID- 3085086 TI - Tumor cell autocrine motility factor. AB - A cell motility-stimulating factor has been isolated, purified, and partially characterized from the serum-free conditioned medium of human A2058 melanoma cells. We term this activity "autocrine motility factor" (AMF). AMF has the properties of a protein with an estimated size of 55 kDa. At concentrations of 10 nM or less, AMF stimulated the random or directed motility of the producer cells. However, AMF is not an attractant for neutrophils. Amino acid analysis of the purified AMF protein revealed a high content of serine, glycine, glutamic acid, and aspartic acid residues. The activity of AMF was not replaced or blocked by known growth factors such as epidermal growth factor or type beta transforming growth factor. Mechanistic studies showed that AMF stimulated the incorporation of [3H]methyl into cell membrane phospholipids after incubation with [methyl 3H]methionine with a sustained increase in the methylation of phosphatidyldimethylethanolamine to phosphatidylcholine. In contrast, AMF did not affect the incorporation of [1,2-14C]choline into phosphatidylcholine. AMF was produced in large amounts by three different clones of ras oncogene-transfected metastatic NIH 3T3 cells but not by the nontransformed parental cells. AMF may play a major role in the local invasive behavior of tumor cells and may also facilitate the concerted invasion by groups of tumor cells. PMID- 3085087 TI - Trans-acting amplification mutants and other eggshell mutants of the third chromosome in Drosophila melanogaster. AB - We report on the characterization of five third chromosome mutations with strong effects on the formation of the eggshell or chorion. Three mutations, defining two loci, result in substantially reduced follicle cell-specific amplification of the major chorion structural genes and, hence, in underproduction of the corresponding mRNAs and proteins. The other two mutations, though displaying structural chorion abnormalities, appear to have no significant effect on amplification and to express normally the major chorion structural genes. The possible nature of these mutations is discussed. PMID- 3085088 TI - Photoreactivation rescue and hypermutability of ultraviolet-irradiated excisionless Drosophila melanogaster larvae. AB - There is accumulating evidence suggesting that expression of genes for repair of UV damage to DNA in mammals and fish is regulated developmentally. Therefore, the activity of excision repair and photoreactivation in vivo in young larvae of Drosophila melanogaster was examined in a strain carrying the mutation mus201 that was unable to carry out excision repair. The photoreactivation activity in first-instar larvae was so high that UV-induced lethality in excision-less larvae was almost completely rescued by posttreatment with fluorescent light. Excision repair activity in first-instar repair-proficient larvae was so high that UV irradiation was scarcely able to produce somatic eye-color mutations. In contrast, excisionless larvae showed a high incidence of somatic eye-color mutation after UV-irradiation, and this incidence was reduced to the spontaneous level by posttreatment with fluorescent light. Incorporation of a postreplication repair-defective mutation into the excisionless strain decreased the incidence of UV-induced somatic mutations by a factor of 3. The analogous repair dependence of UV mutagenesis in Drosophila and Escherichia coli is discussed. It is proposed that UV-induced somatic mutations in excisionless Drosophila larvae are caused primarily by pyrimidine dimers and that a constitutive, error-prone pathway for filling daughter-strand gaps opposite dimers is, at least partly, responsible for the fixation of mutations. PMID- 3085089 TI - Formal proof that different-size Lyt-2 polypeptides arise from differential splicing and post-transcriptional regulation. AB - We recently isolated the gene and a cDNA clone for the mouse T-cell surface antigen Lyt-2 and showed that Lyt-2 is homologous to the human Leu-2 (T8) antigen and that the gene encoding it is a member of the immunoglobulin gene superfamily. By screening a mouse thymus cDNA library with the Lyt-2 cDNA clone, we isolated two classes of cDNA clones, alpha and alpha', which differ by 31 base pairs. Comparison of the alpha cDNA with genomic sequence data indicates that there are five exons encoding Lyt-2: a fused leader/immunoglobulin variable region-like exon, a spacer region exon, a transmembrane exon, and two cytoplasmic exons. The alpha' cDNA clones lack the first of the two cytoplasmic exons and have a direct splice from the donor splice site of the transmembrane exon to the acceptor of the second cytoplasmic exon. This splice changes the reading frame for the second cytoplasmic exon, causing a stop codon shortly after the splice so that the alpha' cDNA clone codes for a peptide 25 residues shorter than the alpha cDNA encoded peptide. We have constructed expression vectors with alpha and alpha' cDNAs and have shown that L-cell transfectants of these produce Lyt-2 polypeptides of the predicted sizes and that these associate as homodimers on the cell membranes. We found the two species of mRNA corresponding to alpha and alpha' cDNAs at equal levels in thymus RNA by using S1 nuclease analysis. Although lymph node T cells have only the alpha form of Lyt-2 protein, S1 nuclease analysis shows that lymph nodes have about 20% alpha' mRNA relative to alpha. Thus, Lyt-2 is regulated at RNA processing, translational, and/or post translational steps. PMID- 3085091 TI - Low-dimensional chaos in an instance of epilepsy. AB - Using a time series obtained from the electroencephalogram recording of a human epileptic seizure, we show the existence of a chaotic attractor, the latter being the direct consequence of the deterministic nature of brain activity. This result is compared with other attractors seen in normal human brain dynamics. A sudden jump is observed between the dimensionalities of these brain attractors (4.05 +/- 0.05 for deep sleep) and the very low dimensionality of the epileptic state (2.05 +/- 0.09). The evaluation of the autocorrelation function and of the largest Lyapunov exponent allows us to sharpen further the main features of underlying dynamics. Possible implications in biological and medical research are briefly discussed. PMID- 3085090 TI - Influence of delayed immune reactions on human epidermal keratinocytes. AB - The epidermal changes that occur in human cutaneous immune responses have been investigated in the tuberculin reaction and in the lesions of tuberculoid and lepromatous leprosy and cutaneous leishmaniasis. In each situation, there was a dermal accumulation of monocytes and T cells, and the epidermis exhibited thickening. In the tuberculin response, the thickness of the epidermis sometimes doubled in 48-72 hr, and this was attributed to increases in both size and number of keratinocytes. In addition, the phenotype of the keratinocytes changed from Ia to Ia+. Similar changes in keratinocyte Ia-antigen expression occurred in the epidermis overlying untreated tuberculoid leprosy and cutaneous leishmaniasis lesions, but not in lepromatous leprosy. We suggest that one or more epidermal growth factors may be generated in the course of a delayed immune reaction in the dermis. PMID- 3085092 TI - Sensitivity of gap junctional conductance to H ions in amphibian embryonic cells is independent of voltage sensitivity. AB - In vertebrate embryos gap junctional conductance (gj) is reduced by transjunctional voltage (Vj) and by cytoplasmic acidification; in each case sensitivity is comparable to those of other channels gated by voltage and ligand receptor binding. We show here that the mechanisms by which Vj and intracellular pH (pHi) gate gj are apparently independent. Partial reduction of gj by lowering pHi neither attenuates nor enhances further reduction by Vj. Certain drugs irreversibly (glutaraldehyde, 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) or reversibly (retinoic acid) abolish dependence of gj on pHi without appreciably affecting kinetic properties of voltage dependence or the shape of the steady state Vj-gj relation. These findings suggest that the mechanisms by which pHi and Vj act on the gap junction are at least partially distinct and presumably involve separate regions of the junctional macromolecules. PMID- 3085093 TI - Separation and properties of cellular and scrapie prion proteins. AB - Purified preparations of scrapie prions contain a sialoglycoprotein of Mr 27,000 30,000, designated PrP 27-30, which is derived from the scrapie prion protein [Mr, 33,000-35,000 (PrP 33-35Sc)] by limited proteolysis. Under these same conditions of proteolysis, a cellular protein of the same size (PrP 33-35C) is completely degraded. Subcellular fractionation of hamster brain showed that both PrP 33-35Sc and PrP 33-35C were found only in membrane fractions. NaCl, EDTA, and osmotic shock failed to release the prion proteins from microsomal membranes. Electron microscopy of these microsomal fractions showed membrane vesicles but not prion amyloid rods. Detergent treatment of scrapie-infected membranes solubilized PrP 33-35C, while PrP 33-35Sc aggregated into amyloid rods; the concentration of PrP 33-35C was similar to that recovered from analogous fractions prepared from uninfected control brains. The apparent amphipathic character of the PrP 33-35Sc may explain the association of scrapie infectivity with both membranes and amyloid filaments. PMID- 3085094 TI - Fc receptor triggering induces expression of surface activation antigens and release of platelet-activating factor in large granular lymphocytes. AB - Triggering of large granular lymphocyte (LGL) Fc receptor with a specific monoclonal antibody (AB8.28) linked to an insoluble matrix induces cell activation, as witnessed by expression of HLA class II (DR and DQ) molecules and interleukin 2 receptor. Moreover, this event is accompanied by a concomitant release of platelet-activating factor by LGL. We conclude that the Fc receptor molecule identified by mAb AB8.28 represents a trigger for LGL activation. PMID- 3085095 TI - Structural homologies among the hemopoietins. AB - A group of cytokines characterized by a common set of target cells--namely, the pluripotential hemopoietic stem cells or their cellular derivatives--share similarities in the amino acid sequence at their N terminus or in the putative signal peptide immediately prior to the published N terminus. Murine P-cell stimulating factor (PSF), murine and human interleukin 2 (IL-2), murine and human granulocyte-macrophage colony-stimulating factor (GM-CSF), human erythropoietin, and human interleukin 1 beta all share alanine as the N-terminal amino acid and have some similarities in the succeeding three or four amino acids. In the case of murine PSF and GM-CSF, the six N-terminal amino acids are readily cleaved from mature molecules and are lacking from the N-terminal amino acid sequences reported initially. A sixth cytokine, colony-stimulating factor 1, has an alanine followed by a similar pattern of five amino acids at the end of the putative signal peptide. GM-CSF and IL-2 have more extensive homology, about 25% of residues being identical in three regions that comprise about 70% of the molecules. Only minor similarities of uncertain significance were found among the complete amino acid sequences of the other cytokines. Although its evolutionary origin is uncertain, the homology around the N terminus may provide a structural marker for a group of cytokines active on the pluripotential hemopoietic stem cell and its derivatives. PMID- 3085096 TI - Developmental regulation of a gene that encodes a cysteine-rich intestinal protein and maps near the murine immunoglobulin heavy chain locus. AB - Mouse and rat small intestinal cDNA libraries were screened for recombinants derived from mRNAs whose concentration changed during the transition from suckling to weaning. cDNAs transcribed from a 570-nucleotide-long mRNA were isolated. Dot blot hybridization analyses of RNA recovered at various stages of rat gastrointestinal ontogeny indicated that the concentration of this mRNA begins to increase during the mid-suckling period, reaching a peak during weaning. There is considerable variation in the relative amount of this mRNA in adult tissues, with highest levels encountered in the rat small intestine and colon. Its concentration in duodenum, jejunum, and ileum is approximately the same. It is more concentrated in villi than in crypts. The rat mRNA encodes a 77 amino acid, 8.55-kDa polypeptide that has seven cysteine residues. This cysteine rich intestinal protein (named CRIP) has two internal repeated sequence blocks. Computer-assisted comparisons of CRIP to proteins of known function disclosed that it is homologous to certain ferredoxins. Southern blot analyses revealed that sequences homologous to the rat gene are present in sea squirt, fish, bird, and human DNA, indicating that this gene is highly conserved and that related proteins may be present in many if not all vertebrates. Recombinant inbred mouse strains were utilized to show that the CRIP gene is closely linked to the immunoglobulin heavy chain constant region locus, Igh-c, on chromosome 12. CRIP mRNA is a molecular marker for the suckling-to-weaning transition of rodent intestinal development. The cloned cDNA may be a useful probe for identifying factors that regulate intestinal development during this period. PMID- 3085097 TI - Single-stranded plasmid DNA in Bacillus subtilis and Staphylococcus aureus. AB - Plasmid pC194 was found to exist in a double-stranded and a single-stranded DNA form in Bacillus subtilis and Staphylococcus aureus. This single-stranded DNA was found as a circular molecule of the same size as the parental monomer and corresponded to only one of the two DNA strands. It represented one-third of plasmid copies. Single- and double-stranded DNA copies in similar proportions to the above were detected for five other S. aureus plasmids (pC221, pC223, pE194, pT127, and pT181) and one B. subtilis plasmid (pHV416). S. aureus plasmid pUB110 and Bacillus cereus plasmid pBC16 were, in contrast, predominantly double stranded. PMID- 3085098 TI - Transformation of the cyanobacterium Anacystis nidulans 6301 with the Escherichia coli plasmid pBR322. AB - Anacystis nidulans 6301 has been transformed in the light to ampicillin resistance with the plasmid pBR322. Permeaplasts prepared by 2-hr treatment of cells with lysozyme and EDTA are transformed with a 50-fold higher efficiency than that observed for cells. beta-Lactamase is present in A. nidulans transformed either with pBR322 or the plasmid pCH1 as evidenced by hydrolysis of the beta-lactam ring of Nitrocefin in extracts of transformants. beta-Lactamase also can be immunoprecipitated from extracts of [35S]methionine-labeled pBR322 transformants and coprecipitates with ribulose-bisphosphate carboxylase. Expression of the carboxylase is apparently amplified in pBR322 transformants as is that for several soluble proteins in pCH1 transformants. Chromosomal DNA per cell is increased about 6-fold after transformation of A. nidulans 6301 with either pBR322 or pCH1. A 4.3-kilobase-pair plasmid can be isolated from pBR322 transformants in addition to the endogenous plasmids pUH24 and pUH25. PMID- 3085099 TI - Preferential expression of variable region heavy chain gene segments by predominant 2,4-dinitrophenyl-specific BALB/c neonatal antibody clonotypes. AB - The B-cell repertoire in neonatal mice contains predominant clonotypes that are reproducibly expressed at particular times after birth. We have isolated and sequenced heavy and light chain cDNA clones from three 2,4-dinitrophenyl-specific neonatal hybridomas. Two of these hybridomas (TF2-36 and TF5-139) express idiotypes (Ids) that predominate during the first days after birth, and the third hybridoma (TF2-76) expresses an Id that predominates during the second week after birth. The heavy (H) chain variable (V) region of the TF2-76 hybridoma protein is encoded by a member of the 7183 VH family, one of eight families of murine VH genes that have been defined by Brodeur and Riblet [Brodeur, P. H. & Riblet, R. (1984) Eur. J. Immunol. 14, 922-930]. Members of this family have been found to undergo a disproportionately high frequency of rearrangement in fetal and neonatal liver pre-B-cells. Because the 7183 VH family is located close to the H chain joining (J) region gene segments, JH, other workers have proposed that VH rearrangement frequency is related to distance from the JH segments. However, the two earlier-appearing predominant clonotypes expressed by TF2-36 and TF5-139 hybridoma proteins utilize a member of the 36-60 VH family, probably VH 1210.7, which is located distal to the JH gene segments on chromosome 12. Since 20-30% of day 3 dinitrophenyl-specific B cells express either the Id(TF2-36) or the Id(TF5 139), the VH 1210.7 gene must be utilized at high frequency early in development. These results indicate that the utilization of rearranged VH segments is strongly influenced by factors other than distance from JH. PMID- 3085100 TI - Involvement of Lyt-2 and L3T4 in activation of hapten-specific Lyt-2+ L3T4+ T cell clones. AB - The murine T-cell surface molecules Lyt-2 and L3T4 play a role in the activation of antigen-specific T cells. The currently accepted model for the function of these molecules proposes that Lyt-2 and L3T4 increase the overall avidity of the interaction between the T-cell antigen receptor and antigen in association with the major histocompatibility complex (MHC) molecules on the antigen-presenting cell. We have used two unusual Lyt-2+ L3T4+ class II MHC-restricted T-cell clones to test whether Lyt-2 can substitute for L3T4 when the T-cell antigen receptor is class II MHC-restricted. Monoclonal antibodies against L3T4 profoundly inhibited antigen-induced lymphokine production by both T-cell clones. Anti-Lyt-2 monoclonal antibody had no effect. These results strongly suggest that L3T4 and the class II-restricted T-cell antigen receptors are physically close during antigen recognition, probably as part of a multimolecular complex from which Lyt 2 is excluded. The ability of L3T4 but not Lyt-2 to participate in such a complex with class II-restricted T-cell antigen receptors may explain the striking correlation between class II restriction and L3T4 expression in the peripheral T cell pool. PMID- 3085102 TI - Regulation of interleukin 2 receptors on T cells from multiple sclerosis patients. AB - Receptors for interleukin 2 (IL-2) are absent on resting T lymphocytes and are induced by antigenic and mitogenic stimulation. After a limited time (8-12 days), these receptors on normal T cells are down-regulated despite the presence of receptor-saturating concentrations of IL-2. We report here that both antigen- and mitogen-induced T-cell lines and clones obtained from peripheral blood and cerebrospinal fluid of multiple sclerosis patients show prolonged expression of IL-2 receptors. This expression is coincident with a prolonged responsiveness to the proliferative effects of IL-2. In addition, Leu 3+, IL-2 receptor-positive T cell clone from the cerebrospinal fluid of a multiple sclerosis patient has been established and maintained for more than 1 year without IL-2. This clone has some morphologic and histochemical properties of T cells transformed or infected by human T-lymphotropic virus type I. PMID- 3085101 TI - Site-directed mutagenesis of an invariant amino acid residue at the variable diversity segments junction of an antibody. AB - Structural analysis of 21 murine A/J antibodies specific for the hapten p azobenzenearsonate (Ars), and bearing the major cross reactive idiotype (IdCRI), has revealed an invariant amino acid residue, serine, encoded by the variable diversity gene segments junction of the heavy chain. To test whether this serine residue is essential for Ars binding, we changed it either to alanine or to threonine by oligonucleotide-directed mutagenesis of a heavy chain gene. Genes containing the mutations were separately introduced into mouse hybridoma cells producing the homologous light chain, and the resulting proteins were tested for antigen binding and idiotypic expression. Whereas the serine to threonine mutant retains full antigen binding activity, the serine to alanine mutant does not bind either to Ars-bovine serum albumin-Sepharose or to the Ars-tyrosine hapten. Both mutants show the same reactivity as wild type towards a series of anti-idiotypic antibodies. These results suggest that a hydroxyl group at the variable-diversity gene segments junction of A/J anti-Ars antibodies is essential for antigen binding. PMID- 3085103 TI - A DNA insertion/deletion necessitates an aberrant RNA splice accounting for a mu heavy chain disease protein. AB - The human heavy chain disease protein BW is an immunoglobulin mu-chain variant whose amino terminus is initiated at the fifth amino acid of the first constant region domain. We cloned and analyzed both rearranged heavy chain alleles from BW leukemic cells to determine the molecular basis for this deleted protein. The phenotypically excluded heavy-chain allele possessed two intermediate recombinations of separate variable-diversity (V-D) and diversity-joining (D-J) junctions, neither of which were expressed. The productive allele, responsible for the mu chain, had a complete V-D-J4 recombination but as a result of a single base deletion possessed stop codons within the variable region. More important, a small DNA insertion/deletion eliminated the J4 donor splice site. This necessitated an aberrant RNA splice between the leader region and the first constant region domain creating a shortened 2.35-kilobase muRNA. A recognition sequence for signal peptidase predicted a cleavage at the fifth amino acid of the first constant region domain. These molecular events are responsible for the truncated mu chain that lacks a variable region and fails to assemble light chains. PMID- 3085104 TI - Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: serine-262 of the delta subunit is labeled by [3H]chlorpromazine. AB - The membrane-bound acetylcholine receptor from Torpedo marmorata was photolabeled by the noncompetitive channel blocker [3H]chlorpromazine under equilibrium conditions in the presence of agonist. Incorporation of radioactivity into all subunits occurred and was reduced by addition of phencyclidine, a specific ligand for the high-affinity site for noncompetitive blockers. The delta subunit was purified and digested with trypsin, and the resulting fragments were fractionated by reversed-phase HPLC. The labeled peptide could not be purified to homogeneity because of its marked hydrophobic character, but a combination of differential CNBr subcleavage and cosequencing of partially purified fragments enabled us to identify Ser-262 as being labeled by [3H]chlorpromazine. The labeling of this particular residue was prevented by phencyclidine and thus took place at the level of, or in proximity to, the high-affinity site for noncompetitive blockers. Ser-262 is located in a hydrophobic and potentially transmembrane segment termed MII. PMID- 3085107 TI - Rapid selection of viable transplantable human fetal pancreatic islets by trypan blue exclusion. AB - A rapid method of separating viable from nonviable human fetal pancreatic islets prior to transplantation is needed to quantify grafted tissue and optimize the possibility of successful treatment of diabetes mellitus in the recipient. After incubation with 0.04% trypan blue in isotonic Krebs-Ringer buffer solution for 15 min, the percentage of islets that excluded trypan blue was found to correlate well with fractional stimulated insulin secretion rates. The incubation procedure did not alter the subsequent insulin secretory capacity of the islets. Trypan blue exclusion rapidly and reliably identifies viable functional islet tissue prior to transplantation. PMID- 3085106 TI - Isolation and characterization of human factor VIII: molecular forms in commercial factor VIII concentrate, cryoprecipitate, and plasma. AB - Human factor VIII has been isolated from a high purity factor VIII concentrate by immunoaffinity chromatography and HPLC on Mono Q gel. Two fractions of factor VIII were obtained with a specific activity of approximately equal to 7000 units/mg. The major fraction contained eight peptide chains of 200, 180, 160, 150, 135, 130, 115, and 105 kDa plus one doublet chain of 80 kDa. The minor fraction contained one peptide chain of 90 kDa plus the chain of 80 kDa. Both fractions were activated by thrombin to the same extent. Amino-terminal amino acid sequence analysis was performed on the 180-kDa, 130-kDa, and 90-kDa chains and showed an identical amino-terminal sequence in these chains. Each chain from 200 kDa to 90 kDa was linked to one 80-kDa chain by a metal-ion bridge(s). Studies on factor VIII in plasma and cryoprecipitate, prepared and gel filtered in the presence of protease inhibitors, showed that one 200-kDa plus one 80-kDa chain were the only or dominating chains in the materials and may represent native factor VIII. The results indicated that all chains from 180 kDa to 90 kDa are fragments of the 200-kDa chain. All of these more or less fragmented chains form active factor VIII complexes with the 80-kDa chain. PMID- 3085105 TI - Inhibitors of protein and RNA synthesis cause a rapid block in prostaglandin production at the prostaglandin synthase step. AB - Inhibitors of protein or RNA synthesis prevented prostaglandin (PG) production in isolated skeletal muscles, brain, and spleen. Incubation of rat muscles with cycloheximide prevented the stimulation of PGE2 production induced in vitro by the Ca2+ ionophore A23187 and in vivo by injection of endotoxin. Cycloheximide also inhibited the stimulation by arachidonic acid of PGE2, PGF2 alpha, and prostacyclin. These observations suggest that the block in prostanoid production results from a loss of PG synthase activity (EC 1.14.99.1). These effects were detectable within 10 min after exposure of the muscle to cycloheximide. The degree of inhibition of PG production correlated with the degree of inhibition of protein synthesis. Other inhibitors of protein synthesis, puromycin and emetine, also prevented conversion of arachidonate into PGE2 in these tissues, but they did not inhibit purified PG synthase. Exposure of muscles to actinomycin D for 20 min also reduced PGE2 production from arachidonate by 90%. Thus, both the PG synthase and its mRNA appear to be inactivated rapidly (t1/2 less than 10 min) in muscle and other mammalian tissues. The block in PG production induced by inhibitors of protein and RNA synthesis may account for their antipyrogenic actions and certain of their other physiological effects. PMID- 3085108 TI - Influence of carbohydrate side chains on activity of tissue-type plasminogen activator. AB - When messenger RNA (mRNA) from both untreated and phorbol ester-treated melanoma cells is translated in simple reticulocyte lysates, tissue-type plasminogen activator can be immunoprecipitated by an affinity-purified antibody as a approximately 52,000 mol wt protein, with no detectable biological (plasminogen activating) activity. When the reticulocyte lysate system is supplemented with a preparation of microsomal membranes, biological activity becomes detectable and a 63,000 mol wt protein can be immunoprecipitated with the same antibody. Furthermore, when natural tissue-type plasminogen activator (mol wt approximately equal to 70,000) is incubated with different glycosidases, distinct alterations in the electrophoretic mobility of the molecules are observed, together with alterations in the level of biological activity. While treatment with neuraminidase and beta-galactosidase caused decreases in activity, alpha mannosidase caused an increase. These results suggest that the carbohydrate part of the molecule can influence its biological behavior. PMID- 3085109 TI - Metabolism of arachidonic acid by hamster trachea lack of stimulation by A23187. AB - The metabolism of arachidonic acid has been studied using hamster trachea in short-term organ culture. To study endogenous substrate utilization, tissue lipids were labeled with [3H]-arachidonic acid, whereas exogenous substrate turnover was assessed by the addition of 100 microM [14C]-arachidonic acid to the medium. Both exogenous and endogenous arachidonate were converted primarily to 6 keto-PGF1 alpha and PGE2, with varying amounts of an unidentified non-polar product noted. Production of the prostanoids increased steadily with time up to 24 hours. No significant generation of lipoxygenase products was found. Release of incorporated labeled arachidonic acid was nearly linear with time, resulting in the transfer of about 10% of the total label into the medium after 24 hours. About 3% of the total label was converted to prostaglandins. In the presence of 10 microM A23187, release of label was increased by only 25 to 60% relative to the control. Analysis of labeled compounds in the medium showed that this increase resulted from increased release of unchanged arachidonic acid, and that the yield of oxygenated products was the same as from the control incubations. PMID- 3085111 TI - Erythrocyte lithium transport during lithium treatment in patients with affective disorders. AB - Erythrocyte lithium transport mechanisms--lithium-sodium countertransport (LSC), lithium-potassium cotransport (LPC) and passive lithium efflux (PLE)--were measured in 46 patients with bipolar affective disorder on prophylactic lithium therapy and in 20 healthy control subjects. Maximal velocity of LSC measured at saturating intracellular lithium concentration was lower in the patients than in the controls; this may concur with previous reports on possible links between impaired activity of LSC and bipolar affective illness. When measured at therapeutic lithium concentration, LSC was 4 times lower and Km for LSC was 5 times higher in lithium-treated affective patients than in control subjects. The in vivo erythrocyte:plasma lithium ratio was inversely correlated with LSC in lithium-treated patients; higher ratios were found in females than in males. No differences were found between affective patients and control subjects in other erythrocyte lithium transport measurements. The values for lithium transport were not related to age, duration of lithium therapy, concomitant neuroleptic treatment, hypertension or obesity. Lower activity of LSC was found in patients with lithium-induced thyroid enlargement than in the other patients. The results obtained are discussed in the light of contemporary findings concerning erythrocyte lithium transport mechanisms in affective disorders and other conditions. PMID- 3085110 TI - Some properties of lipoxygenase activities in cytosol and microsomal fractions of mouse epidermal homogenate. AB - Lipoxygenase activity in microsomal fraction of mouse epidermal homogenate was characterized in comparison with cytosol lipoxygenase activity. The major activity was identified as 12-lipoxygenase in microsomal fraction as well as in cytosol fraction by the analyses with high-performance liquid chromatography and gas chromatography-mass spectrometry. Apparent Km values of cytosol and microsomal 12-lipoxygenase for arachidonic acid were 5.0 microM and 6.2 microM respectively. Apparent Vmax values were 14 pmol/min/mg protein for the cytosol enzyme and 32 pmol/min/mg protein for the microsomal enzyme. Net activities of cytosol and microsomal 12-lipoxygenase were 214 and 109 pmol/min/g wet tissue, respectively. Both cytosol and microsomal lipoxygenase activities were neither dependent on calcium nor ATP. Carbon monoxide failed to affect these enzyme activities. There were considerable differences either in the effect of glutathione or in the sensitivities toward several lipoxygenase inhibitors, indicating that the cytosol and the microsomal 12-lipoxygenase activities are derived from two different enzymes. Alternatively, the differences could be attributable to the different microenvironments of these enzymes. PMID- 3085112 TI - Dynamic total fluorescence and anisotropy decay study of the dansyl fluorophor in model compounds and enzymes. PMID- 3085113 TI - Photodynamic action in Stentor coeruleus sensitized by endogenous pigment stentorin. PMID- 3085114 TI - Unilateral substantia nigra lesions and schedule-induced polydipsia. AB - The present experiment investigated the effects of unilateral 6-hydroxydopamine lesions of the substantia nigra (SN) on schedule-induced polydipsia (SIP). Lesions were made in either the "dominant" or "non-dominant" hemisphere as defined by an amphetamine rotation test. It was found that unilateral lesions of either the "dominant" or "non-dominant" SN significantly reduced SIP and also significantly impaired somatosensory responsiveness as indicated by the "tactile extinction test." Somatosensory neglect was significantly greater following a lesion in the "dominant" hemisphere than "non-dominant" hemisphere. PMID- 3085115 TI - Interaction between circadian and caloric control of feeding behavior in the rat. AB - Feeding at the beginning of the night is probably dependent on the rat's immediate energy requirements while feeding at the end may have an anticipatory function. This latter feeding peak may be mainly controlled by a circadian pacemaker. The aim of this study was to investigate the relative contribution of satiety signals and circadian pacemakers in the control of feeding behavior. Food intake was monitored after infusion of liquid food into the stomach during several parts of the day-night cycle to prevent a possible influence of oral sensations. It is demonstrated that intragastric infusion is more effective in suppressing intake during daytime and the first half of the dark phase than during the second half of the dark phase. Suppressions of food intake are mainly due to delaying the first occurrence of food ingestion, whereas the size of that meal is less affected. During the last period of the night no significant delay could be brought about. These experiments suggest that in the rat a circadian pacemaker dominates feeding motivation during the end of the night thereby strongly interacting with caloric control of feeding behavior. PMID- 3085116 TI - Tormentic acid, a new hypoglycemic agent from Poterium ancistroides. PMID- 3085117 TI - [Epilepsy and pregnancy--principles of therapy]. AB - Special aspects of antiepileptic therapy during pregnancy in epileptic women are described. A monotherapy should be preferred. Due to changes in the pharmacokinetics of antiepileptic drugs, plasma level checks must be performed every four weeks during early pregnancy. The possible teratogenetic effects of anticonvulsants and other factors tending to increase of malformation rate are discussed. An explanation is given for the use of prophylactic folic acid and Vitamin K treatment in connection with antiepileptic therapy. The benefits of counselling prior to pregnancy are discussed. PMID- 3085118 TI - [Prenatal growth of children of epileptic mothers]. AB - In this study 67 children of 59 females with epilepsy and on anticonvulsants were investigated. Children of epileptic women on medication with Primidon are of lower weight and have smaller heads than children from epileptic mothers without medication and children from parents without epilepsy. PMID- 3085119 TI - [Electroencephalographic value of acoustic stimulation within the scope of the diagnosis of forms of cerebral seizure in childhood and adolescence]. AB - In this report we represent the phone-stimulation as an important method of provocative to activate the bioelectric potentials of brain, if epileptic seizures will be appeared in age of childhood and youth. The method ist able to demonstrate irritations of the reticulothalamic system. The information on the activity of the substantia reticularis will be demonstrated by the bioelectric reaction under phone-stimulation. PMID- 3085120 TI - [EEG findings as a principle of military medicine disability evaluation in conditions following craniocerebral injuries]. AB - 295 expert opinans of the NVA (National People's Army) in conditions after craniocerebral traumas for which an EEG findings was present were subjected to an retrospective analysis to determine the importance of EEG for export opinion. In 59.3% of cases EEG was significant for expert opinion, but was of prime importance only in 1.3%. In 161 expert opinions the total damage of the body was determined. This gave the possibility of a statistical correlation of individual EEG findings with the extent of the body damage. Mean percentage values of the individual degrees of severity of EEG changes could be calculated on the basis of these data. The great importance of EEG for military medical opinion could also be confirmed in comparison with 8 other clinical data and findings. PMID- 3085121 TI - Arthur Schnitzler and the fate of mothers in Vienna. PMID- 3085122 TI - Edmond: is there such a thing as a sick play? PMID- 3085123 TI - Lacan's linguistic unconscious and the language of desire. PMID- 3085124 TI - Kohut's case of Mr Z: overcoming countertransference in self psychology. AB - This paper has attempted to discover if the two analyses of Mr. Z by Kohut do in fact substantiate the clinical efficacy of his theoretical model. A brief overview was presented, as were critical assessments. The major point was developed, that a creative working-through of a complementary countertransference was largely responsible for the success of a second analysis after a first phase was seriously undercut by interfering material which rigidified the therapist's interpretation. It was concluded by noting how Kohut's need to overcome the countertransference played a vital role in catalyzing the evolution of his new theory. PMID- 3085125 TI - The analyst's space. AB - The space the analyst creates in his consulting room gives expression to the most primitive elements in his personality. It does this despite, and even by means of, the professional conventions it incorporates. This phenomenon is first apparent in Freud's office where the space of the psychoanalytic situation originated. Here the room itself--filled with the antiquities he collected so passionately--met important narcissistic/symbiotic needs. In this sense it encodes a very early, unanalyzed level of relationship with his mother. It is suggested here that these phenomena, visible in Freud's office, are continuing elements of the analytic frame. Because of the character of the analyst and the structure of the relationship, the room becomes a mise-en-scene in which the narcissistic/symbiotic layers of both participants' characters are played out. Failing to recognize this may lead the analyst to treat seemingly regressive behavior as resistance and to intervene at developmental levels the patients has not achieved. Indeed, such "regressions" can only be understood as products of the situation itself. Phenomenologically, the analyst has become the corner in which he took refuge as a child; the corner to which the patient now comes for sanctuary. Because this connection is unconscious it cannot be called an alliance. Rather, it is a fortuitous interlocking that--like mother-child symbiosis--constitutes a matrix for new growth. PMID- 3085127 TI - Tolstoy, narcissism, and the psychology of the self: a self-psychology approach to Prince Andrei in War and Peace. PMID- 3085126 TI - Infantile omnipotence and grandiosity. AB - A distinction is made between infantile omnipotence and grandiosity. The retention of the former is considered necessary for health and the latter is considered pathological. The former is described as feeling comfortable though it can also be perceived both subjectively and objectively as irrational. The latter is viewed as ultimately distressing, though it can be subjectively experienced as necessary. Grandiosity is seen as a defense against repressed omnipotence. The repression of omnipotence appears to be caused by parents who are threatened by its power. Ways of making the distinction between omnipotence and grandiosity are discussed. Means of treatment and clinical examples are given. PMID- 3085128 TI - Tennessee Williams: the incest-motif and fictional love relationships. PMID- 3085129 TI - Effects of cholecystokinin and caerulein on human eating behavior and pain sensation: a review. AB - Since the mid-1970s, evidence has accumulated that cholecystokinin (CCK) has a role as a neuromodulator or neurotransmitter in the central nervous system as well as in the periphery. CCK has been shown to have a variety of effects on gastrointestinal functions and is one of the main candidates for a role as a peripheral negative feedback signal to stop feeding behavior. CCK produces satiety not only in animals but also in man: it reduces appetite and activation arising from the preparation of a meal and inhibits intake of liquid and solid food in both lean and obese subjects. The closely related peptide caerulein has similar effects. The site of action of peripherally administered CCK seems to be on an abdominal organ innervated by gastric vagal branches and relayed to the brain by afferent vagal fibres, since selective gastric vagotomy blocks the satiety effect, but pharmacological antagonism of vagal motor effects or lesions of the ventromedial hypothalamus do not. CCK also may have a role in the regulation of pain perception. In mice, CCK and caerulein were shown to produce a decrement in response to noxious stimulation after peripheral and central administration. In man, caerulein was demonstrated to relieve pain originating from biliary and renal colic as well as from cancer and ischemia. A series of studies in healthy man revealed that caerulein also alleviates experimentally induced cutaneous pain. Data from animal studies suggest that CCK-like peptides not only are able to produce analgesic effects on their own, but also are involved in the modulation of opioid systems mediating analgesia. Further study of these effects of CCK should elucidate the regulatory connections between the life-sustaining functions of feeding and pain sensation. PMID- 3085130 TI - Changes in gonadotropin regulation in both behavioral and phenotypic disturbances of sexual differentiation in men. AB - Determinations of gonadotropins and testosterone were performed in 22 men with hypospadias (H), seven male-to-female transsexuals (T) and in 16 normal men (N), all of similar age. The response of serum FSH and LH to GnRH was determined in six subjects in each group. Oligospermia was found in five of 13 patients with H. All patients with transsexualism revealed normospermia. Both the patients with H and with T had significantly higher mean serum concentrations of LH than the normals (H: 16.96 +/- 13.83 mIU/ml; T: 15.30 +/- 6.50 mIU/ml; vs 5.73 +/- 3.66 mIU/ml in N). Also, an exaggerated response of LH to GnRH was found in both H and T. No negative correlations were demonstrated between serum LH and testosterone in either the H or the T. Rather, higher mean serum LH occurred together with higher mean serum testosterone in severe H. A significant elevation of basal serum FSH was found in H (H: 7.24 +/- 2.14 mIU/ml vs N: 4.84 +/- 1.65 mIU/ml), which might be related to underlying gonadal injury. No increase of serum basal FSH concentration was found in T patients, but the FSH response to GnRH was higher than in N. It is concluded that hypospadias, a phenotypic disturbance of sexual differentiation, represents a less-specific change in the gonadotropin regulation, while male transsexualism reveals hypergonadotropism with a specifically increased evocability of gonadotropins not coexisting with signs of gonadal injury. PMID- 3085131 TI - Effects of mecamylamine on human cigarette smoking and subjective ratings. AB - Multiple measures of cigarette smoking, subjective effect and physiological effect were collected during 90-min test sessions in normal volunteers. Before sessions subjects received oral doses of mecamylamine (2.5, 5.0, 10, 20 mg) or placebo. Each dose and placebo was given three times in a randomized block sequence. Mecamylamine increased several measures of cigarette smoking, including number of cigarettes, number of puffs per cigarette, and expired air carbon monoxide level. Mecamylamine also produced modest, dose-related decreases in standing blood pressure and increases in standing heart rate. The subjective effects produced by mecamylamine were not characteristic of those of psychoactive drugs. Mecamylamine appears to have increased cigarette smoking by decreasing the effective dose level of nicotine available from cigarette smoking. PMID- 3085132 TI - Mesolimbic dopamine and its control of locomotor activity in rats: differences in pharmacology and light/dark periodicity between the olfactory tubercle and the nucleus accumbens. AB - To compare the functions of the lateral olfactory tubercle (OT) and the medial nucleus accumbens (ACC), dopamine (DA), (3,4-dihydroxyphenylimino)-2-imidazoline (DPI), and ergometrine were injected into the brain of rats familiarized with the experimental cage in which locomotor activity was assessed. In all tests a volume of 0.5 microliter per side was used. Both DA (1-10 micrograms) and apomorphine (1 10 micrograms) increased locomotor activity when injected into the OT; similar injections into the ACC produced inconsistent effects. The OT effects were short lasting, dose-dependent and antagonized by haloperidol (0.5-2.5 micrograms) in a dose-dependent manner. DPI (1-10 micrograms) too produced an increase when injected into the OT; this response was long-lasting, dose-dependent and potentiated by ergometrine (0.1-1.0 microgram). Ergometrine (0.1-1.0 microgram) dose-dependently increased activity over a period of 200 min in ACC and OT rats, although the response in OT rats was much smaller than that in ACC rats. Only the ergometrine response in ACC rats was dose-dependently suppressed by DPI (1-10 micrograms). ACC rats tested during the light period showed a weak stimulatory response to ergometrine in comparison with ACC rats tested during the dark period; OT rats showed reversed light/dark periodicity. Thus, OT rats significantly differed from ACC rats with respect to locomotor responses to dopaminergic agents, their pharmacological profile and their light/dark periodicity. Evidence is provided that the lateral tuberculum, but not the medial accumbens, is responsible for the stimulatory effect of dopamine and related compounds. PMID- 3085133 TI - Effects of chlordiazepoxide on cued radial maze performance in rats. AB - Effects of chlordiazepoxide (CDP) were examined on the performance of rats in an eight-arm radial maze with four cued and food-baited arms. Two conditions were used; random, with cue location varying over trials, and constant, with the same subset of arms consistently cued. In rats pre-trained to a 60-70% efficiency level (Rewarded entries/Total entries X 100), the effects of CDP (2.5, 5.0 and 10.0 mg/kg, IP) differed according to condition. Efficiency was substantially reduced in the random condition, and types of error were undifferentiated. In the constant cue condition the post-drug drop in efficiency was less marked, and errors were selectively those of re-entry into rewarded arms. In both conditions there was a high incidence of error clusters involving re-entries into both rewarded and non-rewarded arms in the random condition, and rewarded arms in the constant condition. The results suggested that CDP induced a general disruption of information processing rather than a specific impairment of working memory, together with some response perseveration which could occur in the presence or absence of discrimination failure. PMID- 3085134 TI - Behavioural and pharmacological characterization of the mouth movements induced by muscarinic agonists in the rat. AB - Pilocarpine administered in doses of 1.25-10.0 mg/kg (IP) produced a variety of mouth movements in the rat. The most frequent of these movements was a chewing behaviour, which increased up to a mean frequency of over 40 per min at the highest doses. Tongue protrusion and gaping also showed dose-dependent increases. Yawning tended to increase in some doses, though these increases were not significant, and yawning was relatively infrequent. Pre-treatment with scopolamine reduced these responses, while pre-treatment with methyl scopolamine did not. Injections of oxotremorine or arecoline, but not carbachol, produced dose-related increases in mouth movements similar to those produced by pilocarpine. These results suggest that mouth movements in the rat are caused by stimulation of central muscarinic receptors. This may prove to be an important behavioural sign of central cholinomimetic activity. PMID- 3085135 TI - Associative factors in the effects of morphine on self-stimulation. AB - These experiments tested the hypothesis that the suppressing and facilitating effects of morphine on intracranial self-stimulation (ICS) (measured 1 h and 3 h post-injection, respectively) are influenced by associative, non-pharmacological factors. Experiment 1 confirmed previous demonstrations that the facilitation of ICS by morphine (10 mg/kg) develops with repeated drug exposures. Once ICS facilitation had developed, the effect was mimicked by saline injection in most subjects. In a separate group of animals, previous exposure to morphine in the home cage prevented drug-induced facilitation of ICS. Tolerance to ICS suppression developed after repeated pairings of the drug and the ICS chambers, but not when the drug had previously been received in the home cage. Experiment 2 examined the effect of low (0.3, 1, 3 mg/kg) doses of chronic morphine on ICS. Facilitation was observed with 1 and 3 mg/kg, but only after repeated testing. Naloxone (0.1 and 1 mg/kg) failed to reverse facilitation in a number of these subjects. In Experiment 3, animals receiving their daily injections of morphine were allowed to self-stimulate only at 3 h post-injection (when ICS facilitation is usually maximal), rather than at 1 h and 3 h post-injection. ICS facilitation was not observed, even with repeated testing. These data indicate that the facilitation of ICS by morphine is the outcome of a learned association between drug administration and the ICS procedure, rather than the invariable result of opiate receptor activation. Repeated exposure to morphine is required for the initial establishment of ICS enhancement, but the subsequent expression of this behavior is not directly related to opiate receptor activity. PMID- 3085136 TI - Fluphenazine plasma levels in patients receiving low and conventional doses of fluphenazine decanoate. AB - Plasma fluphenazine concentrations (FLU) were measured in 45 patients with schizophrenic disorders who participated in a double-blind comparison of 5 and 25 mg fluphenazine decanoate (FD). The rise in plasma level of FLU 24 h after a "test dose" was significantly correlated with steady state FLU concentration at 12 weeks (for 5 mg patients, r = 0.45, P = 0.04; for 25 mg, r = 0.78, P = 0.005). Patients who had low FLU at baseline required nearly 6 months to reach a steady state when they received 25 mg. Patients who received 5 mg and had low FLU at baseline continued to demonstrate relatively low plasma levels for the entire 1st year. Although the mean FLU at 6 months was lower for patients who relapsed during the subsequent 18 months (0.57 ng/ml for relapsers vs 1.01 ng/ml for nonrelapsers), this difference was not statistically significant. When plasma levels from both dosage groups were combined, FLU at 12 weeks correlated significantly with factor scores for akinesia (r = 0.52, P = 0.002) and BPRS cluster scores for retardation (r = 0.52, P = 0.002). These results indicate that the measurement of fluphenazine plasma levels may be useful in determining when patients treated with FD are receiving drug doses which are likely to cause discomforting side effects. PMID- 3085138 TI - Circadian rhythm of serotonin transport in human platelets. AB - The circadian rhythm of serotonin active transport in human platelets was investigated in ten healthy men, aged 27-35 years. Blood was collected at 08.00, 14.00, 20.00, 02.00 and 08.00 hours the next morning. Simultaneous evaluation of the mean platelet volume, platelet distribution width, platelet distribution skewness and platelet number in whole blood was performed. Km and Vmax for serotonin transport varied considerably among individuals over 24 h. However, the mean values and distribution of these kinetic parameters were reduced at 02.00 hours. All platelet size or number parameters were stable and normal over 24 h; therefore, the reduction in mean Km and Vmax values at 02.00 h is not related to morphological platelet differences but either to platelet intrinsic factors or plasmatic variables. Knowledge of the affinity and capacity of serotonin transport throughout the diurnal cycle is important for future comparisons with depressed patients as well as other hormonal rhythms in patients and healthy humans. PMID- 3085137 TI - Adinazolam, a new triazolobenzodiazepine, and imipramine in the treatment of major depressive disorder. AB - This study evaluated the clinical efficacy and safety of a new triazolobenzodiazepine, adinazolam, and imipramine in 40 patients with carefully diagnosed major depressive disorder. Overall, adinazolam was found to be as effective as imipramine. In addition, when patients with more severe, melancholic, subtype of depression were examined, adinazolam was also as effective as imipramine. With the exception of sedation, adinazolam patients demonstrated fewer overall adverse events than imipramine subjects. These results suggest that adinazolam may represent an interesting antidepressant compound. PMID- 3085139 TI - Acute morphine dependence: effects observed in shock and light discrimination tasks. AB - Alterations in shock discrimination accuracy in the rat, indicative of hyperalgesia, have been noted 1-3 days following a single injection of morphine. To establish the extent to which these "withdrawal-like" effects were specific to the shock discrimination paradigm, rats were trained in two separate discrimination tasks. The discriminative stimuli (SD,s) for correct lever presses were mild electric shocks of different intensities in one task and were short duration lights over the levers in the other. After achieving comparable accuracy levels in the two tasks, the animals were injected SC with 30 mg/kg morphine sulfate and performance levels assessed 1, 2, 3, and 7 days later. Shock discrimination accuracy was significantly enhanced on post-morphine day 2, while accuracy in the light position task was not significantly affected on any of the post-morphine test days. The results indicated that increased pain sensitivity, as well as other signs of dependence, can occur following acute exposure to morphine. PMID- 3085141 TI - A comparison of the effects of RO15,1788 and chlordiazepoxide on hot-plate latencies, acoustic startle, and locomotor activity. AB - RO15,1788, (a selective benzodiazepine antagonist) and chlordiazepoxide (an anxiolytic 1,4-benzodiazepine) produced time-dependent and dose-dependent effects on various indices of sensory-motor function. RO15,1788 increased hot-plate latencies at doses (10-60 mg/kg) that had no effect on locomotor activity. Furthermore, the increased hot-plate latencies were observed 15, but not 30, 60, or 120 min after injection of 10 mg/kg RO15,1788. In contrast, chlordiazepoxide (2.5, 5.0, 10.0, 20.0 mg/kg) produced a dose-dependent increase in response times on the hot-plate, which appeared to be related to the depressant effects of this compound on motor activity. CDZ significantly decreased overall motor activity in a dose-related manner, with the two lower doses decreasing activity approximately 75% relative to controls. RO15,1788 (10 mg/kg) also decreased the magnitude of the acoustic startle response measured over 20 stimulus presentations. The startle response was significantly depressed during each of four 5-trial blocks. The magnitude of both the first and the largest response recorded was also decreased by this compound. Chlordiazepoxide (2.5 mg/kg) significantly decreased the magnitude of the startle response only during the first block of five stimulus presentations. These results are discussed in terms of the involvement of benzodiazepine-mediated processes in the modulation of sensory function and behavioral reactivity to biologically-relevant information. PMID- 3085140 TI - Comparison of the metabolism of the three antidepressants amitriptyline, imipramine, and chlorimipramine in vitro in rat liver microsomes. AB - The metabolism of the tricyclic antidepressants amitriptyline (AMI), imipramine (IMI), chlorimipramine (CMI) and some of their metabolites was studied in vitro in isolated liver microsomes of female Spraque-Dawley rats. Nine metabolites of AMI, seven metabolites of IMI, and 11 metabolites of CMI were quantitatively determined with high-performance liquid chromatography. The main metabolic reactions, mediated by an NADPH generating system, were hydroxylation, demethylation, and N-oxidation. The ratio of these reactions was different for the three drugs. AMI was hydroxylated more than CMI and CMI more than IMI. The order for demethylation was CMI greater than AMI = IMI, the order for N-oxidation IMI greater than CMI less than or equal to AMI. The substrate dependence of metabolism was investigated. Demethylation and N-oxidation increased proportionally to increasing substrate concentrations, whereas formation of hydroxylated metabolites became saturated (in the concentration range of 10(-6) 10(-5) M). The in vitro metabolism was compared with the in vivo metabolism in humans, reflected by the plasma concentrations of these drugs and their metabolites. A good agreement in metabolic pathways was found. PMID- 3085142 TI - Metabolic fate of CGS 8216, a benzodiazepine receptor antagonist, in rat and in man. PMID- 3085143 TI - Orbital lymphomas and pseudolymphomas: treatment with radiation therapy. AB - A retrospective analysis of 16 patients with orbital lymphoma or pseudolymphoma from 1961-1984 was undertaken to evaluate the use of radiation therapy. Pathologic assessment confirmed that four patients had benign pseudolymphoma, and 12 patients had true malignant lymphoma, including two with advanced disease at presentation. With a median follow-up of 4 years, the local control rate with radiation therapy was 100%, although the two patients with advanced disease died of lymphoma 26-33 months after irradiation. While doses of 1,600-2,000 cGy appear adequate for pseudolymphoma, for lymphoma a dose of 3,000-4,000 cGy is necessary. Subconjunctival lesions can be treated in a single anteroposterior field; retroorbital lesions require an additional lateral field. PMID- 3085144 TI - Histochemistry and development. 26th symposium. Maastricht, The Netherlands, 26 30 September 1984. PMID- 3085145 TI - The cellular distribution of histone H5 in embryonic and adult tissues of Xenopus laevis and chicken. AB - The cellular distribution of histone H5 in embryonic and adult tissues of Xenopus laevis and chicken has been established with monoclonal antibodies to histone H5. Both in Xenopus and in chicken, the protein has presumably a more widespread cellular distribution than hitherto expected but is absent in most embryonic tissues. At least in Xenopus its presence seems not to be restricted to amitotic cells. Arguments will be put forward histone H5 in these animals should be considered as a H1(0) type of histone and that analogous to mammalian H1 degree this protein plays a role in differentiation. PMID- 3085147 TI - The pubertal sex-specific development of zonation of fatty acid synthase in rat liver. PMID- 3085146 TI - Dynamics of intracellular structure and cell determination during early development. PMID- 3085148 TI - Plasticity of the phenotype of cells derived from the embryonic foregut. PMID- 3085149 TI - Embryonic cholinesterase in the chick limb bud. PMID- 3085150 TI - [Development of connective tissue in mouse skeletal muscle]. AB - The development of the connective tissue in the dorsal forelegs of mouse embryos and sucklings was investigated with the aid of immunofluorescence and electron microscopy. Collagen type III is visible earlier in the muscular connective tissue than collagen type I. However, it seems that collagen does not play a fundamental role in the organization of the muscular tissue. The occurrence of collagen is rather an indication of the mechanical development of the muscles. In early embryos (day 13 to day 15) some desmosome-like cell contacts are visible between fibroblasts and myoblasts, as well as myotubes. PMID- 3085151 TI - Regression of the interdigital tissue during the formation of the digits. PMID- 3085152 TI - Determination, differentiation and migration of non-neuronal neural crest derived cells. AB - After heterotopically grafting premigratory neural crest cells from quail embryos to the wing buds of chicken embryos, Schwann cells, non-epidermal melanocytes and epidermal melanocytes develop in the wings of the host embryos. This indicates that these neural crest derived cell populations are determined before the onset of emigration of neural crest cells from the crest. Epidermal melanocytes of donor origin are found essentially distally from the grafts, whereas non epidermal melanocytes and Schwann cells are found proximally and distally therefrom. If the apical ectodermal ridge is removed from wing buds that have received a graft of neural crest cells, the directionality of the migration of epidermal melanocytes is lost. This indicates that the apical ectodermal ridge might account for the directional movement of epidermal melanoblasts. This situation is compared to myoblasts that behave in a similar way within the avian embryonic wing bud. PMID- 3085153 TI - Lectin coated colloidal gold as a marker for mesoderm formation in mammalian embryos, cultured in vitro. AB - A simple in vitro culture system for mammalian embryos of pre-somite to 30-somite stages is described, in which mouse and rat embryos are used. The rat embryo culture turned out to be more successful for periods longer than 8 hr. The formation of mesoderm and mesectoderm was studied in these embryos by labeling the primitive streak and neural crest with lectin-coated colloidal gold, that was injected into the amniotic cavity with a micro-injection system. PMID- 3085154 TI - The demonstration of acetylcholinesterase in plastic sections. Its application as a marker of early neuronal development. AB - In this paper a histotechnical procedure with respect to the demonstration of acetylcholinesterase in Technovit 7100 (a recently developed GMA) sections is described. From fixation up to embedding several procedural steps were varied and tested, resulting in a suitable procedure. The embedded tissue or sections can be stored for months at 7 degrees C with only a slight reduction of the enzymic activity. The enzyme also appears relatively temperature resistant and independent of section thickness (2-10 microns). The enzymic activity remains constant during incubation. The technique has been applied to our subject of study in order to qualify and quantify several aspects of the development of neuroblasts. PMID- 3085155 TI - [Hemoprotein absorption and peptidase patterns of visceral yolk sac epithelium during development of the rat]. PMID- 3085156 TI - Developmental action of a neuronal peptide on a peptidergic neuron. PMID- 3085157 TI - Spatial domains within the early Xenopus laevis embryo revealed by in situ hybridization and monoclonal antibodies. PMID- 3085158 TI - Melanin in the inner ear: micromorphological and microanalytical investigations. AB - Melanin-pigments are found in various parts of the inner ear, especially in the neighbourhood of those epithelia that are believed to be involved in the secretion and/or absorption of endolymphatic fluid. Microprobe analysis (LAMMA, X ray) measurements were performed in different parts of the inner ear in tissues containing melanin. The tissues were shock-frozen, freeze-dried and embedded in Earle's medium (Spurr). The semi-thin sections used for microprobe analysis were cut dry in a conventional ultramicrotome and mounted on copper grids. Experimental manipulation of the endolymph ionic composition (increased Na+) stimulated the migration of melanosomes from the perinuclear region into the dendritic processes and the rearrangement of the dendritic processes in a close vicinity of the presumably transporting epithelia. The intracellular ion measurements showed the affinity of divalent ions for melanin (Mg++, Ca++, Sr++ and Ba++). It is proposed that melanin represents a physiologically important "reservoir" for essential trace elements and by its binding/release may play a key role in the enzymatically controlled processes of ionic pumps. PMID- 3085160 TI - Concepts and problems in the study of the development of the nervous system. AB - This introductory paper outlines the problems and concepts dealt with in a workshop organized by the German Histochemical Society on developmental aspects of the nervous system. Because this workshop also included demonstrations of techniques, it also includes a discussion of some practical problems in the study of the development of the nervous system. PMID- 3085159 TI - Analysis of cell communication mechanisms involved in the induction of the stem cell of the mesodermal bands in embryos of Patella vulgata (Mollusca). PMID- 3085161 TI - The formation of the neural tube in rat embryos, cultured in vitro, studied with teratogens. AB - With rat embryos cultured in vitro, two mechanisms are studied which are involved in the elevation and apposition of the neural walls: the mesoderm compartment and the "purse string" of the neurectoderm. The first is counteracted using hyaluronidase injected into the head-folds, the second using cytochalasin B or D, injected into the amniotic cavity. All teratogens cause malformations. Hyaluronidase produces inversion of the head-folds, and the cytochalasins cause eversion. Injection of both hyaluronidase and cytochalasin, however, results in a near to normal closure of the head-folds. PMID- 3085162 TI - Histochemistry of puberty. A multidisciplinary study in the rat. AB - A displacement of structures in the hypothalamic region of the rat has been reported in previous papers. 1 micron granules located in neuroblast like cells containing catalase activity (which were detected by enzyme histochemical methods) undergo a shift from the median eminence (at day 22 after birth) towards the ventromedial part of the hypothalamus (at day 35 after birth). This displacement terminates in the medio-basal part of the arcuate nucleus (at day 55 after birth). A similar displacement of dopaminergic fluorescent perikarya has been described following the same route, with the same time sequence. Neonatal application of monosodium glutamate (MSG) leads to an acceleration of the displacement of both the catecholaminergic and the catalase containing perikarya. However after day 25 (after birth) all fluorescent perikarya disappear whereas the catalase containing cell survive when they finally reach the arcuate area. PMID- 3085163 TI - Some aspects of the development of the peripheral autonomic nervous system in the abdomen and the pelvis of the rat. Preliminary results. AB - The development of the relation of the left vagus nerve with the esophagus and the stomach and the relation of the pelvic plexus with the urinary bladder during the last week before birth has been studied by means of the AChE in toto method (Baljet and Drukker 1975, Bloot et al. 1984). It has been established that the gastric branches can be traced as far as the greater curvature until the 18th day. On the 18th day the stomach increases as much in size that on the 19th day these branches can not be traced so far any more. The growth pattern of the left vagus nerve, the stomach and the esophagus has been visualized graphically. In contrast to the previous observations on the stomach the urinary bladder increases gradually in size. However the nerve branches which run towards the bladder show a sudden increase in length on the 20th day after fertilization. PMID- 3085164 TI - An analysis of the central connections of the facial nerve in the mallard using HRP histochemistry. AB - HRP was applied to the facial nerve in the mallard. Afferent connections were compared to a previous degeneration study. Two small projections to the principal sensory trigeminal nucleus and n. interpolaris were present which were not found before. Motor nuclei were identified by injecting HRP into several facialis innervated muscles. PMID- 3085165 TI - Gene expression of liver-specific proteins in the pre- and perinatal period. PMID- 3085166 TI - Pharmacologic approaches to psychogenic polydipsia: case reports. AB - Psychiatric patients presenting with chronic psychogenic polydipsia are often difficult to treat with standard psychiatric interventions. Pharmacologic intervention was attempted in three patients and was successful in one. One patient had a significant and sustained reduction of water intake while on 160 mg of propranolol. One patient did not improve with either propranolol or captopril while a third patient showed no improvement of serum sodium with demeclocycline nor reduction of water intake with propranolol. The potential mechanisms by which these pharmacologic agents might alter thirst in patients with primary polydipsia are discussed. PMID- 3085167 TI - [Tumor promoters]. PMID- 3085168 TI - Results of implantation for T1 and T2 bladder tumours. AB - In the period from January 1972 through December 1983 a total of 123 patients was treated for a bladder malignancy by preoperative external irradiation followed by interstitial therapy. Criteria for selection of patients are solitary lesion, tumour smaller than 5 cm in diameter, state T1 and T2. The majority of patients was in state T2 (89 patients). Persisting local control was achieved in 29 out of 34 T1 cases and in 69 out of 85 T2 cases. The actuarial 10 years survival was 72% for T1 and 34% for T2, with a total disease-free percentage at 10 years of 77% for T1 and 56% for T2. Although in many patients delayed wound healing was noticed, no serious late reactions were seen in skin, bladder or intestine. The causes of death are distant metastases in 13 patients and intercurrent diseases in another 21 patients. PMID- 3085169 TI - Some factors of importance in the radiation treatment of malignant melanoma. AB - The results of radiotherapy in 204 lesions of malignant melanoma in 114 patients were analysed with regard to radiobiological parameters such as total dose, dose per fraction, treatment time, tumour volume and also by various fractionation models. Ninety-seven of 204 lesions showed a complete response (CR) which was persistent in 80. Neither total dose, treatment time nor various modifications of the nominal standard dose (NSD) concept showed any well-defined correlation with response. There was, however, a significant relationship between dose per fraction and response so that high doses per fraction yielded a significantly better response (24% CR for doses less than 4 Gy vs. 57% CR for doses greater than or equal to 4 Gy, p less than 0.001). The lack of influence of treatment time influence allowed an analysis of the data according to the linear-quadratic model yielding an alpha/beta ratio of 2.5 Gy. Using this ratio, an iso-effect for different fractionation schedules could be estimated by the extrapolated total dose (ETD). This was further improved when corrected for the other important parameter which was tumour volume. Thus, an iso-effect formular for malignant melanomas could be calculated as ETDvol = D X ((d + 2.5)/2.5) X M-0.33 where d is total dose and dose per fraction in Gy, respectively and M is mean diameter (cm). The 50% response for ETDvol was found to be 86 Gy. This formular seems to be currently the best way to determine an optimal radiation schedule for effective radiation treatment of malignant melanoma. Treatment of 45 patients with only local or regional disease showed 26 patients who achieved local tumour control with a 56% 3-year survival compared to no survivors among 19 patients in whom the disease could not be controlled locally. This indicated that proper attention should be given to the local treatment of recurrent melanoma since this has important implications for survival. Successful treatment of malignant melanoma may be possible when the special radiobiological features of the disease are taken into account. PMID- 3085170 TI - Specific integral dose: a reconsideration of the integral dose concept. AB - The integral dose represents the total energy deposited by ionizing radiation within a body. Its distribution within normal tissues can be quite variable, depending upon beam energy and radiation technique. A close look at the concept of integral dose in its various forms should be helpful in quantifying the radiation burden borne by healthy tissues outside of the target volume. The integral dose, integral target dose and relative integral target dose will be reviewed, and the concept of specific integral dose will be introduced, using as examples the external irradiation of the urinary bladder employing various energies and techniques, as well as the intracavitary therapy of gynecological cancer using an afterloading apparatus. PMID- 3085171 TI - A 3-D beam subtraction method for inhomogeneity correction in high energy X-ray radiotherapy. AB - Most methods of inhomogeneity correction in high energy X-ray beams, assume an infinite lateral extent of the heterogeneous volumes ("slab models") or require sophisticated time-consuming computer algorithms. We present here a method, developed for parallelepiped inhomogeneities based on a beam subtraction concept combined with a conventional "slab model". Provided that the conventional model is appropriately chosen, this method gives agreement with experimental results better than 1% in most cases. It accounts properly for the scatter modification according to the size and position of the inhomogeneous volume. One example of a computer application is also presented. PMID- 3085172 TI - Electron contamination from photon beam collimators. AB - Photon beam collimators are a source of secondary electrons that contaminate the beams and increase the surface dose. Calculations and measurements of this contamination have been made for 6 MV and 21 MV X-ray beams. Calculations are made using an electron transport model including the production of electrons by the photons and their transport and multiple scatter, both in the collimator and in the air. The variation with collimator material and geometry is investigated. The lowest contamination is obtained for high density and atomic numbers because of the small lateral electron range and large linear stopping power. The collimator geometry is also very important. If the collimator surfaces are hit by the photons, the collimator-produced electrons reaching the phantom may be increased by a factor of 2 or more. Calculations show that the surface dose from these electrons is less than 5% for 21 MV X-rays. This means that the dominating source of contaminating electrons at this energy is the beam flattening filter. PMID- 3085174 TI - [Profitability of the radiological examination of the thorax. Development of thoracic radiology, administered dose, quality control and role of the clinic]. AB - The considerable spreading of chest X-ray (about 50% of all radiological examinations--WHO official report No. 698), and its biological and economic high cost, make interesting the cost/benefit evaluation of this simple and world-wide X-ray examination. The evaluation, highly important although very complex, is concerned with many different problems. The different problems, such as the development of radiological diagnosis in pulmonary diseases, dose of exposure, quality assurance and clinical role are analyzed. PMID- 3085173 TI - Evaluation of acute bioassays for assessing toxicity of polychlorinated biphenyl contaminated soils. AB - Proposed State of California regulations use fish toxicity information as one criterion in municipal or industrial waste hazard evaluation. Static 96-hr bioassays were performed using fathead minnows (Pimephales promelas), blacksmith (Chromis punctipinnis), and glass shrimp (Palaemonetes kadiakensis) exposed to soil experimentally contaminated with up to 500 ppm polychlorinated biphenyl (PCB) capacitor fluid added at a concentration of 500 mg liter-1. Other bioassays were conducted with a 6-day mixing period prior to the bioassay or with acetone added to solubilize the PCBs. No mortality attributable to PCB toxicity was observed in definitive bioassays using the two fish and one invertebrate species. PCB levels leached from soil containing 500 ppm Aroclor 1242 ranged from less than 0.6 to 3.4 ppb in freshwater tests to 3.5 ppb in seawater bioassays. Using these data as the basis for waste classification, soils contaminated with up to 500 ppb PCBs during capacitor spills would be designated nonhazardous. PCBs are known to be environmentally persistent and to bioaccumulate. Acute toxicity tests, therefore, do not adequately evaluate the general toxicity of PCB contaminated soils. Hazardous waste regulations for hydrophobic compounds such as PCBs should instead be based upon chronic toxicity data and should also consider bioaccumulation potential. PMID- 3085175 TI - [The good use of multivariate statistics]. AB - Within a multidisciplinary team, it is important to establish a common language for the statistician and the electroencephalographer. Using an example, we propose a brief introduction to correspondence analysis. Within a set of 8 variables, we show how to isolate a subset of variables which are characteristic either for partial epilepsy or generalized epilepsy. PMID- 3085176 TI - [Cholestasis and total parenteral nutrition]. PMID- 3085177 TI - [Re-breathing as a non-invasive method for the determination of cardiac output]. PMID- 3085178 TI - The effect of schistosomiasis on the activation of aflatoxin B1. AB - This study examined activation of aflatoxin B1 (AFB1) in livers of Schistosoma mansoni-infected and noninfected mice by measuring covalent binding of [3H]AFB1 to cellular macromolecules in vivo and in vitro. During a one week time period after AFB1 treatment of animals, maximal binding of [3H]AFB1 to DNA, RNA and protein in liver occurred during the 1-6 hour period after treatment, with less binding throughout of AFB1 to macromolecules of infected mice. Experiments performed in vitro to determine the capacity of liver microsomes to mediate the binding of AFB1 to calf thymus DNA showed that microsomes from infected mice mediated the binding of less [3H]AFB1 to DNA than those from noninfected animals. PMID- 3085179 TI - Can Encephalitozoon cuniculi cross the placenta? AB - Laboratory rabbits and mice were challenged with Encephalitozoon cuniculi at three different stages of gestation to determine whether the parasite crosses the placenta. No transplacental transmission could be demonstrated. PMID- 3085181 TI - Experimental investigation of the cardiovascular and respiratory effects of increasing concentrations of isoflurane in the dog. AB - The cardiovascular and respiratory effects of the new inhalational anaesthetic agent isoflurane were investigated in dogs. Anaesthesia was induced with thiopentone after premedication with acepromazine. Isoflurane was administered with nitrous oxide and oxygen by spontaneous ventilation after base line values had been determined. Arterial blood pressure decreased as the concentration of administered isoflurane increased. Isoflurane produced a profound and dose related respiratory depression as measured by the increase in end tidal carbon dioxide levels. Isoflurane administration did not produce any visible muscle twitching. PMID- 3085180 TI - Influence of creep feeding and weaning on brush border enzyme activities in the piglet small intestine. AB - The activities of the enterocyte brush border enzymes lactase (beta-D galactoside galactohydrolase, EC 3.2.1.23) and sucrase (sucrose alpha-D glucohydrolase, EC 3.2.1.48) were measured at set percentage lengths along the small intestines of 112 piglets killed between 21 and 32 days of age. The influences on these activities of consumption of creep feed and of weaning were recorded. Weaning at three weeks old resulted in large, rapid reductions in lactase activity at most sites along the small intestine; sucrase activity declined temporarily and then recovered. Minimum values were recorded about four to five days after weaning. Similar changes were observed whether or not creep feed was consumed before weaning. Continued consumption of creep feed by unweaned pigs over the 21 to 32 day period also produced small but significant reductions in lactase activities. The large loss of digestive enzyme activities at brush borders in weaned animals coincided with a reduced ability to absorb xylose and to checks in growth rate in otherwise healthy piglets. PMID- 3085182 TI - Respiratory responses of the domestic fowl to low level carbon dioxide exposure. AB - Respiratory function in the restrained, conscious domestic fowl was measured using a non-invasive technique and computer aided analysis to examine respiratory flow, and in-dwelling arterial catheters to monitor blood carbon dioxide levels. The effects of two low ranges of inspiratory carbon dioxide (0.2 to 1.0 per cent and 0.25 to 2.25 per cent) were studied, simulating levels of carbon dioxide that may occur in commercial poultry units and representing a mild environmental stress for the birds. A linear increase in minute volume with inspiratory carbon dioxide was observed, due primarily to increases in tidal volume. Arterial carbon dioxide (PaCO2) tension also rose as the inspiratory carbon dioxide concentration was raised, but higher inspiratory carbon dioxide levels were required to affect significantly blood carbon dioxide concentration than to modify respiratory parameters. Variation was observed in the individual bird's response to carbon dioxide (bird X carbon dioxide interaction), suggesting that resting values of the respiratory parameters measured were important in determining the bird's ventilatory response to carbon dioxide. PMID- 3085183 TI - Uveal effusion in Hunter's syndrome. Evidence that abnormal sclera is responsible for the uveal effusion syndrome. AB - A patient with Hunter's Syndrome (systemic mucopolysaccharidosis type II) was evaluated for bilateral uveal effusion syndrome. The right eye showed a circular peripheral choroidal detachment for 360 degrees. The left eye showed a larger circular peripheral choroidal detachment and an exudative retinal detachment. Evaluation of the sclera during combined sclerectomies and sclerostomies of the left eye revealed markedly thickening sclera and a reduced number of vortex veins. The surgery resulted in complete resolution of the choroidal detachment and exudative retinal detachment of the left eye. The presence of uveal effusion in Hunter's Syndrome, in which the sclera has been histologically demonstrated to be abnormally thickened, supports the recently proposed pathophysiology of the uveal effusion syndrome. PMID- 3085184 TI - [Hemodynamic effects of intravenous nitroglycerin and of its combination with dopamine in experimental heart failure in the dog]. PMID- 3085185 TI - Oxygen binding functions of blood and hemoglobin from the Chinese pangolin, Manis pentadactyla: possible implications of burrowing and low body temperature. AB - We measured O2 equilibria of adult blood and of 'stripped' (cofactor-free) hemolysates from adult and newborn Manis pentadactyla, in order to assess the implications of the burrowing habit and the low deep-core temperature in pangolins, and to discern the mechanisms for maternal-fetal O2 transfer. At pH 7.4 and body temperature (33 degrees C) the blood O2 affinity was significantly higher than in similarly sized non-burrowing, 'normothermic' mammals (P50 = 21 and 33 mm Hg, respectively) indicating an adaptation to hypoxic burrow conditions. This difference is not attributable to a higher intrinsic O2 affinity in the pangolin Hb or to significant differences in its sensitivity to temperature and erythrocytic 2,3 diphosphoglycerate (DPG), but tallies with lower DPG/Hb ratios than generally found in mammals. Stripped adult and newborn hemolysates show similar O2 affinities and pH and DPG sensitivities, but reveal a specific adult Hb that develops after birth, in sharp contrast with the ontogenetic changes in other mammals where specific fetal Hbs are lost after birth. PMID- 3085186 TI - Background activity in pulmonary vagal C-fibers and its effects on breathing. AB - Vagal cooling experiments suggest that the deep slow breathing observed after vagotomy results not only from loss of pulmonary stretch receptor feedback, but also from loss of some unidentified vagal input. To investigate this possibility we cooled the vagus nerves in anesthetized dogs. In dogs breathing spontaneously, the Hering-Breuer reflex was abolished at 7 degrees C, but average expiratory time was unchanged and lengthened only on cooling below 3 degrees C. In artificially ventilated dogs the pulmonary vagus nerves were cooled in the chest and phrenic activity was recorded. Entrainment of phrenic bursts to the ventilator cycle ceased at 7 degrees C, and expiratory pauses shortened; they lengthened again on cooling below 3 degrees C. Cervical vagotomy did not change breathing pattern after the pulmonary vagus nerves were cut. Recording of afferent impulses during cooling showed that at 5 degrees C or less pulmonary vagal input was confined largely to nonmyelinated fibers; at 3 degrees C, background activity in pulmonary C-fibers was still 78% of control whereas myelinated afferents were virtually silent. We suggest that in eupnea low frequency, background activity in pulmonary afferent C-fibers shortens expiratory time. PMID- 3085187 TI - Effects of CO2 and H+ on the ventilatory response to peripheral chemoreceptor stimulation. AB - To determine whether the stimulatory effect of CO2 on the peripheral chemoreceptors is due to molecular CO2, H+ or both we measured steady-state ventilation (Ve) during normoxia in 9 and during hypoxia in 5 chloralose-urethane anaesthetized cats using the artificial brain stem perfusion technique. This technique allows one to manipulate independently the PaCO2, PaO2 and the pHa of the blood in the systemic circulation (peripheral) and the blood perfusing the brain stem (central). Keeping the central conditions constant the H+ and CO2 concentrations in the systemic circulation were changed by i.v. infusion of 0.3 M HCl or 0.6 M NaHCO3 and by giving the animal different CO2 mixtures to inhale. The peripheral H+ concentration ([H+]p) range covered was from 27 to 103 nmol X 1(-1); the peripheral arterial CO2 tension (PaPCO2) ranged from 2.3 kPa to 8.4 kPa. Fitting the data with the function VE = a[H+]p + bPaPCO2 + c revealed that the coefficient b was not significantly different from zero at the 0.05 level during normoxia and hypoxia. The mean value (+/- SEM) found for the coefficient a was 33.0 +/- 3.6 at normoxia and 36.0 +/- 15.4 ml X min-1 X nM-1 at hypoxia. We conclude that the steady-state ventilatory response due to the stimulation of the peripheral chemoreceptors with CO2 is mediated by H+. The effects of molecular CO2 are negligible. PMID- 3085188 TI - Acid-base regulation in prolonged hypoxia: effect of increased PCO2. AB - Conscious rats maintained for 3 wk at PB 370-380 Torr were studied in a chamber where PIO2 was kept at 68-70 Torr at ambient barometric pressure (740-750 Torr). Blood samples were obtained through an arterial catheter. Controls were pair-fed rats maintained at ambient barometric pressure and studied at PIO2 68-70 Torr for 4 h (acute hypoxia) or at ambient PIO2 (normoxia). Arterial blood pH of 3-wk hypoxic rats was not different from that of normoxic rats. Hypercapnia was produced by increasing PICO2 for 4 h. The 3-wk hypoxic rats showed the highest apparent non-bicarbonate buffer value of arterial blood (beta app): 77 mmol/(pH X kg), compared to 38 in normoxia and 43 mmol/(pH X kg) in acute hypoxia. Comparison of beta app at different times of hypercapnia in intact and in nephrectomized rats suggests that the high beta app of prolonged hypoxia is largely due to an increased renal compensation, and, to a smaller extent, to increased chemical buffering. While the extracellular fluid of normoxic and acute hypoxic rats showed a net gain of base of non-renal origin during hypercapnia, the 3-wk hypoxic rats showed a net non-renal base loss, which may be masked by the increased renal compensation. PMID- 3085189 TI - [Nephrotoxic effect of gold sodium thiomalate in rats--ultrastructual observations using electronmicroscopy and X-ray energy dispersive analysis]. AB - The purpose of this study is to demonstrate renal injuries by gold sodium thiomalate (G) with ultrastructual changes and gold deposition in kidney tissue using X-ray energy dispersive analysis (XEDA). Twenty-five mg of G containing 12.1 mg of Au was injected into rats intraperitoneally. The rats were divided into 5 groups. Group 1 was sacrificed 6 hours after the injection of G, and group 2 after 24 hours, group 3 after 72 hours and group 4 after 144 hours. Group 5 consisted of the control-rats which were provided with injections of saline. Gold contents in kidneys, liver, lungs and spleen were measured using the flameless atomic absorption method. XEDA was also performed in order to confirm the gold deposition in tissue. Among the organs, only the kidney showed remarkable changes with increased weight. Group 1 already showed marked azotemia which reached to the maximum level in group 3. The amount of gold content in the organs did not change significantly in spite of a marked reduction of serum gold concentration among the 4 groups. Histological examinations revealed marked degeneration and necrosis of pars recta in proximal tubules, although no prominent abnormalities of glomeruli could be observed. Using an electron microscope, many electron dense particles in lysosome were noticed, mainly in proximal tubules. We also found these particles in lysosome of glomerular epithelial cells. Using XEDA, these electron dense particles were demonstrated to be gold, since characteristic energy of gold was found. In conclusion, the kidney was shown to be the most accumulative organ of gold. G caused acute extensive necrosis of proximal tubules. Gold was demonstrated as electron dense particles in lysosomes mainly in proximal tubules, but also partly in glomeruli. Therefore, it was confirmed that a large amount of G had a strong nephrotoxic effect in rats. PMID- 3085190 TI - [The enteral feeding pump (2)]. PMID- 3085191 TI - [Renal function and carbon dioxide baths]. PMID- 3085192 TI - [Myoclonic cerebellar dyssynergia (Ramsay-Hunt syndrome) and cerebellar telangiectasia]. AB - A 8 year-old girl presented with generalized epileptic seizures followed by the progressive onset of myoclonic jerks, sometimes associated with willed movements, and a static and kinetic cerebellar syndrome without conspicuous intellectual impairment. Death occurred 10 years after the onset of the disorders. There was no family history. Neuropathological studies showed lesions confined to the cerebellum. Diffuse and bilateral telangiectases were present in the cerebellar white matter. They were associated with patchy cortical alterations of the distal parts of some folia involving mainly the granule-cells ans sparing the Purkinje cells. No Lafora bodies and no abnormal lipofuscin storage were observed. The dentate nuclei, superior cerebellar peduncles and red nuclei were normal as were the inferior olives and inferior cerebellar peduncles. The spino-cerebellar tracts were unaffected. This case confirms the hypothesis that dyssynergia cerebellaris myoclonica corresponds only to a clinical entity. It may be encountered in various degenerative or metabolic disorders involving the cerebellum and/or its pathways. To our knowledge the association of a Ramsay Hunt syndrome with a vascular malformation has not been previously reported. PMID- 3085193 TI - Selective primary health care: strategies for control of disease in the developing world. XXIII. Control of infection to reduce the prevalence of infantile and childhood malnutrition. AB - Malnutrition is due to many complex and interacting factors, both biologic and social. This may be why so little has been accomplished in the global efforts to reduce its prevalence and impact. The greatest burden of malnutrition falls on the youngest members of society, and in these infants and children it is closely associated with infectious diseases. Because of multiple effects on host nutrition and metabolism, infections result in nutritional deterioration that must be corrected during convalescence. When this is precluded by limitations in the adequacy and availability of food, and infections are frequent, progressive deterioration in nutritional status occurs, with high morbidity and mortality rates. Measures that reduce the prevalence and nutritional consequences of infection are the most feasible and cost-effective interventions to improve nutritional status of young children at the present time. These measures include immunization, oral rehydration programs for diarrheal disease, promotion of breast feeding, continued feeding during infection, development of adequate weaning foods from mixtures of available local commodities, specific nutrient fortification, growth monitoring, improved environmental sanitation and water supplies, and education. The first seven measures can be introduced immediately in all societies and are basic elements of effective primary health care. The last two, which promise the greatest return in benefits, are the most costly and most difficult to implement. Malnutrition and infection are inseparable and the measures to deal with the former must effect a reduction in the latter if they are to succeed. PMID- 3085194 TI - The meningococcus: a twenty-year perspective. PMID- 3085195 TI - [Chemotherapy of breast cancers. Coordinated evolution of therapeutic schemes from 1975 to 1985]. AB - In 10 years the schemes of medical treatment of breast cancer have progressed in the direction of greater efficacy (balanced multiple associations), improved articulation with other therapeutic tests, increased ease of application (single perfusion) and lower toxicity (especially from the cardiac point of view), which make it possible to extend the indications to less advanced forms. PMID- 3085196 TI - [Diabetic acidoketosis]. PMID- 3085197 TI - [Antidiabetic drugs]. PMID- 3085198 TI - Allergy in childhood. PMID- 3085199 TI - [DRG. Diagnostic related groups. Neither panacea nor sophistry]. PMID- 3085200 TI - Comparative investigations of Latin American trypanosomes with lectins and complement lysis test. AB - Four-days old epimastigote culture forms of different stocks of Trypanosoma cruzi from Colombia, Costa Rica and Mexico as well of Colombian stocks of T. rangeli were tested with 27 lectins and the complement lysis test. While the stocks of T. cruzi and T. rangeli showed common agglutination reactions with the lectins of Canavalia ensiformis and Pisum sativum, only the stocks of T. cruzi were additionally agglutinated by Ricinus communis-120, Glycine maxima, Helix pomatia, Axinella polypoides, Bandeiraea simplicifolia, Bauhinia purpurea, Wistaria floribunda, Abrus precatorius, Aaptos papillata II, Limax flavus and Arachis hypogaea. On the basis of lectin typing, the strains of T. cruzi belong to the PNA-type. While the epimastigote culture forms of T. cruzi stocks were lysed by normal fresh human, rat, chicken, rabbit and guinea pig serum, the culture forms of T. rangeli were only lysed by chicken serum. Mouse serum had no lytic effect on either trypanosome species. Incubation of T. cruzi with neuraminidase did not alter the lytic effect of the sera. The membrane-associated N-acetylneuraminic acid on T. cruzi does not protect the cell surface against the activation of the alternative complement pathway. After treatment of T. cruzi with neuraminidase and subsequent incubation in culture medium, the PNA-type was restored. The cells reacted again with the lectins of Arachis hypogaea, Limax flavus, Aaptos papillata II but not with Triticum vulgaris. PMID- 3085201 TI - When diabetes races out of control. PMID- 3085202 TI - Helping elderly patients resist infection. PMID- 3085203 TI - [Periarticular ossification. Complication of total hip prosthesis]. AB - The authors analyse peri-prosthetic ossification, a complication which can occur in the presence of certain risk factors. Grades I and II calcifications are frequent and do not interfere with the final post-operative result. On the other hand, grades II and IV result in a progressive stiffening of the coxo-femoral joint within one year after the operation. They may be bilateral and can sometimes be responsible for serious handicap. These cases should be re-operated in order to restore joint mobility, but surgical treatment should be completed by radiotherapy according to a defined protocol. Non-steroidal anti-inflammatory agents and diphosphonates also have a preventative action. Subjects at risk (ankylosing vertebral hyperostosis, spondyloarthritis, alcoholism, patients with a history of ossification of the first side) require effective prophylactic treatment. In the authors' own series, 49 cases of ossification were observed in a retrospective analysis of 100 patients, including 6 cases of grades III and IV ossification. They analyse their results in relation to the initial hip pathology treated by prosthesis, but their series is too small to allow an statistically valid conclusions. Complementary studies are required. PMID- 3085204 TI - [Therapeutic sequences calcitonin-EHDP and EHDP-calcitonin in Paget's disease. Histological and biological study]. PMID- 3085205 TI - Hearing in patients in a department for long-term medicine. A further report. AB - Audiological screening was performed in 164 patients, aged 32-89 (median 71) years, in a department for long-term medical treatment. 45% of the patients had a hearing loss exceeding 30 dB HL in the frequency range 500-2 000 Hz (pure-tone average, PTA). The aetiology of the hearing loss was in most cases presbycusis, as the pure-tone thresholds were closely related to the age of the patients. The speech discrimination score for the better ear was impaired (less than 90%) in about 50% of the patients. Nevertheless, only 15% of the patients felt they had a significant hearing handicap. On average, these patients had a hearing loss exceeding 50 dB HL (PTA). The nursing staff estimated about two-thirds of the patients as having normal hearing and only 6% of the patients as having a severe hearing loss. The otologists also underestimated the number of patients with audiometrically impaired hearing. 11% of the patients had a hearing aid, but in nearly half of the patients, the function of the device was defective, either due to flat batteries, incorrect mounting or similar minor defects. A positive effect was observed subsequent to annual 2-hour courses for nurses, focusing on problems in communication with elderly people and on assisting patients who use a hearing aid. PMID- 3085206 TI - In vitro activation of amphibian dermal melanocytes by nicotine. AB - Epidemiologic investigations have shown that nicotine could be a factor causing oral melanin pigmentation in man. Nicotine was therefore tested on amphibian skin melanocytes. Cell reactions were registered by spectrophotometry, in vitro light microscopy, photomicrography and light and electron microscopy. It was found that dermal melanocytes in the toad Bufo bufo and the frog Rana arvalis were activated by nicotine and that this activation was not mediated via beta-adrenergic receptors in melanocytes. PMID- 3085208 TI - A primary extranodal lymphoma associated with IgM-kappa paraproteinaemia: different secretory capacities of cutaneous and circulating lymphoma cells. AB - We report a patient with non-Hodgkin's lymphoma of small lymphocytic type with IgM-kappa monoclonal gammopathy who developed extranodal involvement with orbital and nasal manifestations, followed by generalized subcutaneous nodules. Immunological study disclosed that the peripheral blood and the subcutaneous nodule were both involved in a common monoclonal proliferation of B cells at various stages of differentiation, including secretory cells which accounted for the serum paraprotein. The secretory capacity was far greater in the peripheral blood than in the subcutaneous tissue. These clinical and immunological manifestations might reflect the physiological behaviour of a particular B cell subset which shows a preference for mucocutaneous sites to secrete IgM in the peripheral blood. PMID- 3085207 TI - Thrombocytopenia with thrombocytopathy possibly related to abnormalities of intracellular Ca++ fluxes and followed by the development of leukaemia. AB - A patient is described who presented a thrombocytopenia with thrombocytopathy followed by the development of a leukaemia. The disorder was characterized by decreased aggregation in the presence of ADP, and a lack of aggregation in the presence of arachidonic acid, natural endoperoxide or collagen. In parallel, 14C serotonin release was severely decreased or nil in response to these inducers. Thrombin induced a slightly decreased aggregation and a normal 14C-serotonin release. Thromboxane B2 (T X B2) synthesis was normal after stimulation by arachidonic acid, natural endoperoxide or thrombin showing a normal arachidonate metabolism. In addition, the mepacrine test showed no significant decrease of the number of dense bodies with an average of 4.6 per platelet (versus 5.4 +/- 0.8 sd in controls). Stimulation by ionophore A 23187 failed to induce aggregation, 14C serotonin release, or T X B2 synthesis. Furthermore, in the presence of EDTA, A 23187 did not provoke activation as reflected by 14C-serotonin release or T X B2 synthesis. Thus, in this case of thrombocytopathy, the hypothesis of abnormal intracellular Ca++ fluxes responsible for the defective platelet release phenomenon, was suggested. PMID- 3085210 TI - The sheep erythrocyte receptor and both alpha and beta chains of the human T lymphocyte antigen receptor bind the mitogenic lectin (phytohaemagglutinin) from Phaseolus vulgaris. AB - We have studied the interaction of mitogenic lectins such as phytohaemagglutinin (PHA) and concanavalin A (Con A) with both surface molecules which, by the use of monoclonal antibodies, are known to trigger T-cell mitogenesis. Monoclonal antibodies recognizing the T-lymphocyte receptor for antigen (Ti) and/or its associated structure, CD3, activate T cells. More recently, a second pathway of activation has been described which involves the sheep erythrocyte binding glycoprotein CD2, a surface molecule distinct from Ti-CD3. Lysates from surface iodinated T-leukaemia cell lines were treated with lectin and affinity purified anti-lectin antibodies coupled to protein A-Sepharose. We have shown that eluates from Con A/anti-Con A or PHA/anti-PHA immunoprecipitates contained Ti, since a rabbit anti-T alpha serum, which recognizes the native and denatured forms of the constant region of the alpha chain, immunoprecipitated Ti from these eluates. Furthermore, Ti immunoprecipitated by anti-T alpha serum from lysates of surface iodinated E+ lymphocytes was binding to PHA after elution from the immunoprecipitate. When the purified Ti molecule was reduced and alkylated, allowing the permanent dissociation of its alpha and beta subunits, PHA interacted with both chains, whereas anti-T alpha serum immunoprecipitated the alpha chain only. Altogether, these results demonstrate that PHA interacts with both chains of the T cell receptor for antigen on human peripheral T lymphocytes. With the HPB-ALL tumour line, a similar approach showed that both alpha and beta chains of Ti bind to Con A and Ulex europaeus 1 but not Helix pomatia. Affinity chromatography on immobilized lectins and immunoprecipitation with lectin/anti lectin antibodies were employed to test whether CD2 binds to PHA and Con A. The results show that CD2 from human peripheral T lymphocytes binds both lectins but with a lower affinity for PHA than Con A. PMID- 3085209 TI - Monocyte-regulated hyporesponsiveness of human cord blood lymphocytes to OKT3 monoclonal-antibody-induced mitogenesis. AB - OKT3 monoclonal antibody recognizes surface antigenic structures present on all human mature T lymphocytes and is mitogenic for resting peripheral T cells. Recent reports suggest that these structures are linked to the specific antigen receptor of the T cells and play an important role in T-cell activation. We have tested the mitogenic action of OKT3 on resting lymphocytes from human newborns, their mothers, and unrelated adults. We found that the proliferative response of cord T cells to OKT3 is significantly lower than the response of maternal and adult cells at all doses of the antibody tested (5-1000 ng/ml). This difference was not dependent on culture conditions (source of serum, kinetics induced by the OKT3 antibody, or different proportions of adherent cells in peripheral blood mononuclear leukocytes), and could only to some extent be accounted for by differences in the proportions of OKT3-binding cells between these populations. Removal of adherent monocytes largely diminished the OKT3-induced proliferation of maternal and adult cells, by an average of 70-80%. In contrast, it significantly enhanced the proliferation of cord cells. The proliferative response of cord T lymphocytes to the two polyclonal T-cell activators phytohaemagglutinin and concanavalin A was similar to or greater than that of mothers and other adults. PMID- 3085211 TI - Human peritoneal eosinophils and formation of arachidonate cyclooxygenase products. AB - Human peritoneal eosinophils were obtained from the waste dialysis bags of patients undergoing continuous ambulatory peritoneal dialysis. The number of eosinophils obtained from each bag varied from 3 X 10(7) to 288 X 10(7). The cells were incubated for 1 h in tissue culture medium and prostaglandin E2 (PGE2), 6-keto-prostaglandin F1 (6-keto-PGF1), and thromboxane B2 (TXB2) were determined by radioimmunoassay of the supernatant. The basal release as well as the stimulated release from the purified eosinophils of TXB2 were five times greater than the release of PGE2 and thirty times greater than the release of 6 keto-PGF1. A dose-response curve was achieved for all three cyclooxygenase products with the calcium ionophore A23187. The release of TXB2 was inhibited in a dose-dependent manner by the specific thromboxane A2 (TXA2) synthase inhibitor OKY-1581 and a corresponding increase in PGE2 and 6-keto-PGF1 was obtained. Indomethacin (5.6 X 10(-6) M) inhibited the cyclooxygenase products to almost undetectable levels. PMID- 3085212 TI - Pharmacokinetics of phenoxymethylpenicillin in tonsils. AB - The pharmacokinetics of phenoxymethylpenicillin in tonsillar tissue was studied in 33 patients who underwent tonsillectomy, mainly because of repeated tonsillitis or peritonsillitis. The patients were operated on 30-240 min after an oral penicillin dose of 12.5 mg/kg body weight. The mean serum concentration was 2.8 micrograms/ml for 10 patients operated upon 80-95 min after drug administration. The mean tissue concentration for these patients at the same time was 0.6 micrograms/g. The mean concentration of penicillin in tissue after 240 min was 0.05 micrograms/g. 19% of the serum concentration was recovered in the tonsillar tissue. No significant difference between penicillin concentration in the centre or surface of the tonsils was found. The tissue concentration was calculated to be above 0.03 micrograms/ml for at least 4-5 h. 30% of the patients harboured penicillinase producing bacteria on their tonsils, mainly Staphylococcus aureus. These patients had a lower tissue concentration than those lacking the bacteria, but the difference was not statistically significant (p = 0.095). PMID- 3085213 TI - Gonadotrophin induced effects on human testicular morphology. AB - Ten infertile men were treated with gonadotrophic hormones. The effects on serum hormone concentrations, sperm counts, in vitro conversion of progesterone in testicular biopsies and on testicular morphology, were studied. Gonadotrophin treatment increased serum testosterone concentrations and sperm counts in some patients. In the patients where the in vitro conversion of progesterone in testicular tissue was changed, the Leydig cells also increased in size. In some patients the thickness of the lamina propria decreased during therapy, and a thick lamina propria should not exclude a patient from gonadotrophin therapy. Gonadotrophin therapy may be beneficial in patients with understimulated progesterone conversion in vitro, even in cases without spermatogenesis, provided spermatogonia are present. No harmful effects of hCG/hMG treatment were observed. PMID- 3085214 TI - Reliability of a 99mTc-DTPA gamma camera technique for determination of single kidney glomerular filtration rate. A comparison to plasma clearance of 51Cr-EDTA in one-kidney patients, using the renal clearance of inulin as a reference. AB - In a recent paper we described a method for calculation of single kidney glomerular filtration rate (SKGFR) from the 99mTc-DTPA renogram obtained by gamma camera. Determination of the injected dose and collection of urine or blood was not needed. In this paper the reliability of the method was compared to other methods for estimation of GFR in 20 unilaterally nephrectomized patients. The renal clearance of inulin served as reference measure of GFR. The values for SKGFR obtained from the renograms and from the estimated endogenous creatinine clearances according to serum creatinine concentration and a nomogram were both accurate. The reliability of the renography method was significantly better judged by less variance in the estimates. SKGFR calculated from the plasma clearance of 51Cr-EDTA overestimated the renal clearance of inulin on an average by 11.3%. No difference was found in the variance of the values obtained from the renograms and from the plasma clearances of 51Cr-EDTA compared to the renal clearance of inulin. Apart from the inaccuracy in the GFR values calculated from the plasma clearance of 51Cr-EDTA, the reliability of these two methods was equal. The day to day variation of SKGFR estimated from the renograms in 24 patients (48 kidneys) with SKGFR values from 5 to 76 ml/min was 8.8%. This equals the day to day variation in the plasma clearance of 51Cr-EDTA. PMID- 3085215 TI - [Hypogonadism in males and females]. AB - This comparison of the common and distinctive signs of male and female hypogonadism is intended to acquaint the non-specialist practitioner with some general trends in andrology and gynecologic endocrinology. The author deliberately omits any presentation of rare clinical entities or precise guidelines for investigation and treatment of infertility. PMID- 3085216 TI - Understanding animal development: the roles of gene action and positional information. PMID- 3085217 TI - Gene therapy--so near and yet so far away. PMID- 3085218 TI - Inhibition of development of exoerythrocytic forms of malaria parasites by gamma interferon. AB - A specific DNA probe was used to study the effect of recombinant rat, mouse, and human gamma-interferon (gamma-IFN) on the course of sporozoite-induced malaria infections. In mice and rats infected with sporozoites of Plasmodium berghei, mouse and rat gamma-IFN's strongly inhibited the development of the exoerythrocytic forms in the liver liver cells of the hosts, but not the development of the erythrocytic stages. The degree of inhibition of the exoerythrocytic forms was proportional to the dose of gamma-IFN administered, but was independent of the number of sporozoites used for challenge. A 30 percent reduction in the development of exoerythrocytic forms in rat liver was achieved when 150 units (about 15 nanograms of protein) of rat gamma-IFN were injected a few hours before sporozoite challenge; the reduction was 90 percent or more with higher doses of gamma-IFN. The effect was less pronounced if the gamma-IFN was administered 18 hours before or a few hours after challenge. Human gamma-IFN also diminished the parasitemia in chimpanzees infected with sporozoites of the human malaria parasite Plasmodium vivax. The target of gamma-IFN activity may be the infected hepatocytes themselves, as shown by in vitro experiments in which small doses of the human lymphokine inhibited the development of exoerythrocytic forms of Plasmodium berghei in a human hepatoma cell line. These results suggest that immunologically induced interferon may be involved in controlling malaria infection under natural conditions. PMID- 3085219 TI - Plant phenolic compounds induce expression of the Agrobacterium tumefaciens loci needed for virulence. AB - The virulence loci of Agrobacterium tumefaciens are a set of linked transcriptional units that play an essential role in the early stages of plant tumorigenesis. These loci are induced upon cocultivation of the bacteria with plant cells. Seven phenolic compounds that are widely distributed among the angiosperm plants--catechol, gallic acid, pyrogallic acid, p-hydroxybenzoic acid, protocatechuic acid, beta-resorcylic acid, and vanillin--are able to induce the expression of the virulence loci. These phenolics in combination induce each transcriptional locus of the vir loci. Furthermore, this induction displays similar kinetics and genetic control to that observed during cocultivation of the bacteria with plant cells. PMID- 3085220 TI - Effects of growth hormone-releasing factor in the brain. PMID- 3085221 TI - Amyloidosis and plasma cell dyscrasias: gastrointestinal involvement. PMID- 3085222 TI - Amyloidosis and plasma cell dyscrasias of the musculoskeletal system. PMID- 3085223 TI - [Nutrition for the pregnant and lactating woman]. PMID- 3085225 TI - [Laugh--a nursing prescription]. PMID- 3085226 TI - [What force should be used for aspiration?]. PMID- 3085224 TI - [Whole-body turning of a cervical lesion patient in an ordinary hospital bed]. PMID- 3085227 TI - [Caffeine, stress and anxiety]. PMID- 3085228 TI - [Diseases transmitted by sexual contact]. PMID- 3085229 TI - [Research on artificial skin. Interview by M. Vigy]. PMID- 3085230 TI - Guidelines for the clinical and economic evaluation of health care technologies. AB - The health care system is routinely confronted with promising new technologies. In the past, most new technologies have been integrated into clinical practice without a rigorous demonstration of their effectiveness or efficiency. In order to provide a more rational approach to the adoption and utilization of health technology a comprehensive set of guidelines for both clinical and economic evaluation is proposed. While conceived of as an ideal that is unlikely to be universally met in practice, it is argued that decision making can be improved by striving towards this goal. The clinical guidelines stress the advantages of subjecting major new technologies to randomized controlled trials and insisting upon a demonstration of patient benefit in the application of diagnostic technologies. The economic guidelines stress comparisons with relevant alternative uses of the resources and the assessment of the impact on the quality of life. While application of the guidelines will produce rigorous and useful evidence, the final decisions concerning the allocation of health care resources must rest fundamentally on social value judgements and not solely, or even primarily, on informed expert opinion. PMID- 3085231 TI - Economic aspects of health education. AB - Economic aspects of health education have, to date, received inadequate attention. An economic framework for discussing and evaluating health education is offered, with health education being placed in the already well established economic framework for assessing both health and education respectively. Health education is shown to yield both consumption and investment benefits. The application of cost-benefit analysis and cost-effectiveness analysis to health education activities is explored, and the reasons for the absence of successful applications of the cost-benefit technique to health education programmes are described. The somewhat greater scope for the application of cost-effectiveness analysis is then discussed. A detailed economic evaluation is provided of the North Karelia Project which was concerned with the prevention of cardiovascular disease. The inadequacy of the limited economic evaluation of that project is described and an attempt made to assess the true economic consequences of the project. PMID- 3085232 TI - A framework for evaluating community-based heart disease prevention programs. AB - This paper reviews issues that arise in the evaluation of community-based heart disease prevention programs and offers suggestions for improving future evaluations of these programs. A framework encompassing the evaluation of process, impact and social relevance guides this discussion. The goal of the framework is to divide the question, "do community-based health programs work?", into more easily answered evaluation questions. In doing so, interventions that promote the health of community residents are likely to be designed and implemented successfully. PMID- 3085233 TI - Outbreak of penicillinase-producing Neisseria gonorrhoeae with an African connection. AB - Previous outbreaks of penicillinase-producing gonococcal infection in the United States have generally been attributed to importation of Southeast Asian strains. During July 1982 through July 1983, 110 cases of gonorrhea caused by penicillinase-producing strains were reported in metropolitan Atlanta, Georgia. Among the 53 infected women, 14 (26%) had pelvic inflammatory disease (PID). Compared to other infected women, those with PID experienced a greater delay from the time of last sexual exposure (19.1 vs 8.1 days) to receipt of appropriate antibiotic therapy (P less than .01). At least 22 prostitutes were involved in the outbreak. Sixteen (76%) of 21 isolates tested were serogroup 1A; 15 required arginine and proline for growth; and 17 (81%) possessed a 3.2 megadalton plasmid. Our data suggest that this outbreak was associated with both African and Southeast Asian strains. PMID- 3085234 TI - Coexistence of neurofibromatosis and Marfan's syndrome. PMID- 3085236 TI - Active lupus in a patient receiving long-term hemodialysis. AB - We have described a patient with disseminated systemic lupus erythematosus that became aggressive, active, and life-threatening after eight to ten months of hemodialysis therapy, necessitating high-dose immunosuppressive therapy. PMID- 3085235 TI - Hypercalcemia and reversible renal failure in heavy-chain disease. AB - We have reported a case of gamma heavy-chain disease associated with hypercalcemia and reversible renal failure. After combined chemotherapy the patient remains well after 21 months of follow-up, and serum calcium levels remain in the normal range. This case supports the notion of Kyle et al that heavy-chain disease may present a diverse picture, and documents the first use of aggressive combination chemotherapy in the management of associated moderately severe hypercalcemia and hypercalcemic renal failure. PMID- 3085237 TI - Leukemoid reaction associated with severe diabetic ketoacidosis. AB - A 30-year-old man had severe diabetic ketoacidosis and a leukemoid reaction, which promptly resolved after therapy with intravenous fluids and insulin. There was no evidence of an underlying malignancy or infection. Although a mild leukocytosis may accompany DKA, a leukemoid reaction has not been previously reported to occur with uncomplicated diabetic ketoacidosis. PMID- 3085238 TI - Rib penetration of the intervertebral foraminae in neurofibromatosis. PMID- 3085239 TI - Praziquantel in the acute porphyrias. PMID- 3085240 TI - Ovarian hyperstimulation syndrome. PMID- 3085241 TI - Clinical studies in black women with isolated gonadotrophin-releasing hormone deficiency. AB - Twelve black patients with primary amenorrhoea as a result of hypogonadotrophic hypogonadism were studied to establish the diagnosis of isolated gonadotrophin releasing hormone (GnRH) deficiency. All were eunuchoid with poor development of breasts and pubic hair. Chromosomal complement was female and none had midline facial defects or anosmia. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were low or undetectable, while the levels of other pituitary hormones were normal. Patients did not respond to clomiphene citrate administration, but did bleed in response to an oestrogen/progestagen combination and responded to human menopausal gonadotrophin. This study clearly establishes that isolated GnRH deficiency occurs in black women and suggests that the male:female ratio is different from that in white populations. PMID- 3085242 TI - [Quantification of the fibrinogen degradation products FDP-D and FDP-E in blood, using immunoenzyme analysis]. PMID- 3085243 TI - [Nodular lymphoma with monoclonal proteins in the serum, IgG lambda myeloma and immunoblastic B-cell sarcoma in the same patient. Proliferation from a single cellular clone]. PMID- 3085244 TI - [Lymphocyte subpopulations in the hemophilia A population at the La Coruna regional hospital]. PMID- 3085246 TI - Total body irradiation in Essen--dosimetry and physical treatment planning. AB - Since 1975, in Essen 109 patients received total body irradiation (TBI) prior to bone marrow transplantation. About 80 patients were treated by bilateral 5.7 MeV photon beams. Three new TBI techniques were developed providing precise, homogeneous, reliable and reasonable a. p./p. a. TBI for adults and children. Systematic TBI dosimetry and the beam-zone method enable for individual treatment planning. PMID- 3085245 TI - [Clinical manifestations of childhood diabetes and acidoketosis]. PMID- 3085247 TI - Total body irradiations at the University Hospital of Freiburg. AB - Since 1974, 65 patients have been treated with high dose total body irradiation before bone marrow transplantation. The irradiation technique is described using a 6 MeV-linear accelerator in a small treatment room. PMID- 3085248 TI - Hyperfractionated total body irradiation as part of autologous bone marrow transplantation. AB - On 14 patients with acute leukemia and non-Hodgkin lymphoma autologous bone marrow transplantation (ABMT) was performed together with high dose cyclophosphamide and hyperfractionated total body irradiation. The radiotherapy was given at a total dose of 13.2 Gy distributed over eleven fractions of 1.2 Gy and four days. All eleven patients transplanted in complete remission are alive, among them ten in unmaintained complete remission at a longest observation time of two years. PMID- 3085249 TI - General and specific aspects of experimental dose measurement in total body irradiation (TBI). AB - In magna-field irradiation using high energy bremsstrahlung (photons), i.e. total body irradiation, it is desirable to achieve a homogeneous dose distribution or to realize a planned modification in dose deposition within the target volume. In the Department of Radiology, University of Kiel, for this purpose individually constructed compensators are in routine use for about three years. Some physical and dosimetric aspects of this irradiation technique are described briefly and the experimental test procedure for TBI-compensators is highlighted by several details, for example transmission measurements, radiographies of the compensators and determination of actual dose rates in the midplane of the patient. PMID- 3085250 TI - Description of the TBI procedure for bone-marrow transplantation at the University of Tubingen. AB - The TBI is performed with 8 MV X-rays of a linear accelerator. The procedure is divided into a lateral and a.p./p.a. segment with a weighting factor of 5/6 and 1/6 respectively. For the lateral segment no compensators are employed. Only the upper part of the arms are used to shield the lungs. In the a.p./p.a. segment two or three fields have to be used on account of the small FSD. Here head and neck are shielded depending on the overdosage in the lateral segment. The dose given to the lungs is limited by mantlefield-technique to 10.5 Gy. The total midline dose amounts to 12 Gy and is applicated on three days with two fractions per day. PMID- 3085251 TI - Technique and dosimetry of total body irradiations at Ulm. AB - At the University of Ulm total body irradiation before bone marrow transplantation is given in nine fractions within three days. A total dose of 13 Gy is applied via four fields with 8-MV X-rays. Dose to the lung is limited to 10.5 Gy by means of individually shaped blocks. The homogeneity of dose distributions is improved by the use of compensators for the lower extremities and boli in the head and neck region. Dosimetric data for treatment planning are measured by an ionization chamber and thermoluminescence dosimeters in water and perspex phantoms. In vivo measurements of dose distributions (ionization chamber, TLD) during each fraction allow modifications of compensators and boli in the case of deviations from calculated data. PMID- 3085252 TI - Dosimetric problems associated with total body irradiation. AB - Total body irradiation (TBI), which is carried out with high energy photons at large source distances and with large fixed fields, involves special dosimetric requirements. The dose measurements published thus far on anthropomorphic phantoms have shown that deviations from the dose values calculated with "normal" dose functions occur as a result of completely different scatter radiation distributions. The higher the photon energy selected, the more slight these deviations become. PMID- 3085253 TI - Influence of lung tissue on the dose distribution of high energy photon beams. AB - Dose distributions in unit density (water equivalent), low density (lung equivalent) and heterogeneous (water with regions of lung equivalent) materials are described. While interest is focussed on the inhomogeneous situation the homogeneous cases will provide better understanding. In each case it is shown how primary and scattered photons as well as secondary electrons shape the depth dose curve and the lateral dose profiles. The influence of several parameters like lung thickness and density, distance from interfaces, field size, photon energy etc. is discussed. An investigation on dose calculation methods for inhomogeneous phantoms shows to which extent these are suitable for total body irradiation. Possible improvements require further systematical experiments. Because lung tissue differs from soft tissue only in its density, dose measurements in the lung can be handled in the same way as in tissue equivalent materials. PMID- 3085254 TI - [Feasibility of examining patients with peptic ulcer of the duodenum in a polyclinic]. PMID- 3085255 TI - [Disorders of esophageal motility as a cause of retrosternal pain]. PMID- 3085256 TI - Severity of illness and DRG reimbursement. PMID- 3085257 TI - Sodium cromoglycate in nocturnal asthma. AB - To investigate whether mast cell degranulation was important in producing nocturnal asthma, the effect of a single high dose of nebulised sodium cromoglycate on overnight bronchoconstriction, oxygen saturation, and breathing patterns in eight patients with nocturnal wheeze was examined. The study took the form of a double blind placebo controlled crossover comparison. Treatment with cromoglycate did not reduce the overnight fall in FEV1 or FVC, although it was associated with improved nocturnal oxygenation. This study suggests that mast cell degranulation may not be important in the pathogenesis of nocturnal asthma. PMID- 3085258 TI - Late complications of reversed gastric tube oesophagoplasty. AB - This paper reports two late complications of oesophageal replacement using the reversed gastric tube described by Gavriliu. One patient developed obstruction of the gastric tube and the other a perforation of a diverticulum within the gastric tube, both occurring more than 10 years after the original operation. The occurrence of such complications should be made known to surgeons who are contemplating using this form of oesophageal replacement. PMID- 3085259 TI - Accuracy of gas analysis in lung function laboratories. AB - Fifty lung function laboratories in England and Wales analysed test gas mixtures of carbon monoxide and helium. Most of them also analysed mixtures of oxygen and carbon dioxide in nitrogen. The percentage accuracy of the results was within 1% of the expected value in only 14% of determinations of carbon monoxide concentration, 28% for carbon dioxide, 37% for helium, and 48% for oxygen. The accuracy of ratios of two concentrations of helium and carbon monoxide was better than that of the individual gas samples. Overall the variation in results between laboratories was wide, the coefficient of variation ranging from about 3% for analysis of helium to 9% for carbon dioxide. This variation affected the values calculated for carbon monoxide transfer factor, where 20% were in error by more than 5%, and for the calculated value of the respiratory exchange ratio, where the interlaboratory coefficient of variation was about 10%. Errors in analysis were due to unsatisfactory calibration of analysers; five oxygen analysers had large zero errors; five carbon monoxide analysers and one helium analyser had notably curvilinear calibration curves. Insufficient information was obtained to ascertain the nature of the errors in analysis of carbon dioxide. Given the improvements in instrumentation, these results are evidence for deterioration in analytical standards in lung function laboratories from the standards of 20 years ago. PMID- 3085260 TI - Intra-operative activation of coagulation--a stimulus to thrombosis mediated by vasopressin? AB - Vasopressin infusions in normal volunteers that produce concentrations in plasma comparable to those seen during stress, cause an increase in plasma factor VIII and shortening of the euglobulin clot lysis time (ECLT). We have investigated the relationship between endogenous vasopressin (aVP) release and haemostatic function in 7 patients undergoing major abdominal surgery. Blood samples were taken at nine intervals during the operative procedure. Plasma aVP levels peaked at median values of 51 pg/ml during bowel manipulation and remained elevated on the first post-operative day. Following, and in close temporal relationship with the rise in aVP there were increases in factor VIII coagulant activity, the ristocetin co-factor, von Willebrand antigen, plasminogen activator activity (10(6)/ECLT2) and fibrinopeptide A concentrations with shortening of the activated partial thromboplastin time. The relationship was similar to that seen following infusion of aVP in human volunteers. The results are consistent with the hypothesis that aVP is an important mediator of changes in haemostatic function which accompany stress and might contribute to the thrombotic risk associated with surgical operations. PMID- 3085261 TI - Comparative study of intranasal, subcutaneous and intravenous administration of desamino-D-arginine vasopressin (DDAVP). AB - This study was performed to evaluate the influence of different routes of administration on the efficacy of DDAVP treatment. Ten healthy volunteers received DDAVP intranasally (i.n.), subcutaneously (s.c.) and intravenously (i.v.) in a randomized cross-over trial. Factor XII and high molecular weight (HMW)-kininogen levels increased only slightly after DDAVP administration. The mean increase of factor VIII: C was 3.1 (i.v.), 2.3 (s.c.), and 1.3 (i.n.) - fold over baseline. Ristocetin cofactor (von Willebrand factor antigen) increased 3.1 (2.5), 2.0 (2.3) and 1.2 (1.2) - fold over baseline mean values after i.v., s.c. and i.n. DDAVP, respectively. The half-disappearance time of factor VIII and von Willebrand factor (vWF) after DDAVP ranged from five (factor VIII:C) to eight hours (vWF). The mean increase of fibrinolytic activity was more pronounced after i.v. DDAVP. The antidiuretic effect was moderate with no apparent differences between the routes of application. This study provides further evidence that both i.v. and s.c. DDAVP administration result in an appropriate and reliable stimulation of haemostasis. An additional advantage of s.c. administration is its suitability for home treatment. PMID- 3085262 TI - Effects of arginine vasopressin (AVP) infusions on circulating concentrations of platelet AVP, factor VIII: C and von Willebrand factor. AB - To study the possible role of arginine vasopressin (AVP) in the control of haemostasis AVP infusions at 3 doses (0.1, 0.2 and 0.3 mU/kg/min) were performed in 6 male volunteers. Both plasma and platelet AVP concentrations rose in a dose related manner. At doses of 0.2 and 0.3 mU/kg/min there was an increase in the plasma concentrations of both plasma Factor VIII and von Willebrand factor. The data support the hypothesis that AVP, by interacting with platelets and stimulating factor VIII and von Willebrand factor release, plays a role in the control of haemostasis. PMID- 3085263 TI - The production and characterisation of a panel of ten murine monoclonal antibodies to human procoagulant factor VIII. AB - A panel of 10 murine monoclonal antibodies to procoagulant FVIII has been developed from the fusion of a single spleen. Balb/c mice were injected with a purified preparation of FVIII: Ag, and antibody production in sera and hybrid culture supernatants was monitored using a specific radiometric screening assay. The antibodies all inhibit FVIII clotting activity in normal plasma, and when immobilised on agarose retain their ability to recognise and bind the FVIII procoagulant protein. Studies on protein A-purified immunoglobulins demonstrate a range of properties within the panel of antibodies with regard to species cross reactivity, clotting inhibition and immunoadsorption. The panel of antibodies has been used to screen heat-treated FVIII concentrates for the occurrence of heat induced neoantigens. PMID- 3085264 TI - The influence of DDAVP infusion on the coagulation and fibrinolytic response to surgery. AB - The response of components of the coagulation and fibrinolysis systems to infusion of DDAVP has been examined in patients undergoing elective surgery. In the DDAVP treated group there was a significant increase, compared to control, in plasminogen activator (by fibrin plates p less than 0.005, ECLT p less than 0.0125, by Student's t test) before operation. No difference between groups was seen by either methods in the activator levels in samples 24 h postoperation, whereas a significant drop (p less than 0.002) in protein C concentration was observed at this stage in the treated group. Levels of factor VIII components were significantly higher (p less than 0.005) than control at all stages of operation and a significant shortening (5 sec p less than 0.05) of the APTT was seen at all stages (apart from 24 h samples). DDAVP infusion therefore may exacerbate the hypercoagulable state observed in surgical patients without preventing the (post-operatively) fibrinolytic shutdown. Instead, infusion tends to produce fibrinolytic depletion at the key mid-operative stage. PMID- 3085265 TI - The assay of factor VIII: C in heparinized plasma: a polybrene neutralization method. AB - Factor VIII coagulant activity (VIII:C) has been shown by several investigators to exhibit increased stability in vitro when physiological levels of plasma ionized calcium are maintained by anticoagulation with heparin rather than citrate. An increase in initial activity of VIII:C in heparin over that of VIII:C in citrate has been reported but this has not been confirmed. In order to assay VIII:C in heparinized plasma, the heparin anticoagulant effect must be excluded without interfering with the validity of the assay. A one-stage clotting assay for VIII:C has been developed where heparin is neutralized by Polybrene, a synthetic polymerized quaternary ammonium salt. VIII:C may be accurately measured by this method which satisfies the requirements for a valid assay of parallelism and linearity. PMID- 3085266 TI - The fast-acting inhibitor of tissue-type plasminogen activator in plasma is also the primary plasma inhibitor of urokinase. AB - We have compared the ability of a plasminogen activator inhibitor (PA-inhibitor) in human plasma, to form complexes with radioiodinated tissue-type plasminogen activator (t-PA) and high molecular weight urokinase (HMr-UK). Addition of 125I-t PA (final concentration 10 IU/ml) or of 125I-HMr-UK (2 IU/ml) to a plasma containing 33 U/ml of PA-inhibitor resulted in the rapid formation of a 110,000 Mr complex of 125I-t-PA or a 95,000 Mr complex of 125I-HMr-UK with PA-inhibitor. Upon prolonged incubation of the plasma with 125I-HMr-UK a secondary complex of a Mr of 88,000 was observed, which probably derives from limited degradation of the 95,000 complex. Preincubation of the plasma with unlabelled t-PA, HMr-UK or LMr UK at higher concentrations prevented the subsequent formation of complexes between radiolabelled PAs and the PA-inhibitor. These results thus demonstrate that t-PA and UK form complexes with the same PA-inhibitor. The rate of complex formation of 125I-t-PA or of 125I-HMr-UK with the plasma PA-inhibitor was similar (second order rate constant of association with PA-inhibitor in the order of 10(7) M-1s-1). PMID- 3085267 TI - Evaluation of the cuticle bleeding time in canine haemophilia A. AB - In this paper we describe our clinical experience and results with the cuticle bleeding time test in a colony of cross-bred Labrador retrievers with severe haemophilia A. The dogs have a severe bleeding tendency with a high incidence of fatal haemorrhages in the central nervous system. Homozygous females appeared to be especially prone to this lethal complication. Factor VIII recovery and half life determinations yielded results similar to the data from human studies. The cuticle bleeding time proved to be a good measure of the coagulation defect. The prolongation of the bleeding time could be completely abolished by administration of 10 to 15 units of canine factor VIII per kg body weight. We conclude that the cuticle bleeding time in canine haemophilia provides us with a suitable model for the in vivo study of new therapeutic materials. PMID- 3085268 TI - A sensitive assay, specific for endothelial cell type plasminogen activator inhibitor in blood plasma. AB - A polyclonal antibody raised against plasminogen activator (PA-)inhibitor from endothelial cells fully precipitates the PA-inhibitor in endothelial cell conditioned medium but only a part of the PA-inhibitory activity in blood plasma. This indicates that the PA-inhibitory activity in blood plasma is not due to a single inhibitory component. Performing the assay for PA-inhibitory activity in plasma both in the presence and absence of saturating concentrations of anti endothelial cell PA-inhibitor antibodies, allows the determination of endothelial cell type PA-inhibitor in plasma. The assay gives a linear dose-response curve of amount of plasma added versus t-PA neutralised. Values for endothelial cell type PA-inhibitor in plasma of a group of 20 healthy individuals are in the range of 0.0-16.8 IU/ml and are not normally distributed (median value 3.0 IU/ml). This method also reveals a second, so far unidentified, PA-inhibitory component in human plasma. PMID- 3085269 TI - Isolation and preliminary characterisation of active B-chain of recombinant tissue-type plasminogen activator. AB - Purified 2-chain recombinant tissue-type plasminogen activator (t-PA) was reduced under mild conditions - 10 mM dithiothreitol/5 degrees C/1.5 h - and the two chains were separated by chromatography on lysine Sepharose. The t-PA B chain was fully active as determined by its activity towards the chromogenic substrate S 2288 (H-D-ile-pro-arg p-nitroanilide). Analysis by sodium dodecyl sulphate polyacrylamide gel electrophoresis under reducing or non-reducing conditions revealed a single polypeptide at Mr = 35,000 or 29,000 respectively. In addition, under non-reducing conditions a fibrinolytic band at apparent Mr = 29,000 was present after fibrin zymography. The N-terminal sequence was confirmed as ile-lys gly. The t-PA B chain had a specific amidolytic activity, using S-2288, of 170,000 to 210,000 SU/mg protein. (This compares to a specific activity of the native 2-chain t-PA of 170,000 SU/mg). It resembles urokinase-type plasminogen activator in its inability to be stimulated by fibrin and its dose response on human fibrin plates. However, t-PA B-chain was stimulated to almost the same extent as t-PA by poly-D-lysine. The isoelectric points, at pH 5.6 and 5.7, fall outside the range generally quoted for t-PA preparations (pH 7.8-8.8). PMID- 3085270 TI - Immunohistochemical localization of plasminogen activators in human saphenous veins. AB - Human saphenous veins were analyzed for presence of plasminogen activators (t-PA) in the endothelium of the vessel walls by immunohistochemical techniques. We used a polyclonal rabbit antihuman t-PA antibody, a monoclonal mouse-antihuman t-PA and a goat antibody to low molecular weight urokinase. To demonstrate presence of antigen we used FITC conjugated anti-IgG or the Biotin-Avidin technique. Both monoclonal and polyclonal anti-t-PA demonstrated positive fluorescence in the endothelial layer. Tests for urokinase were negative. The present study thus demonstrated that t-PA was present in the vascular endothelium. This is in accordance with data from earlier histochemical studies for detection of PA activity. PMID- 3085271 TI - Adhesion of human platelets to collagen in the presence of prostacyclin, indomethacin and compound BW 755C. AB - Prostacyclin (1 ng to 2 micrograms per ml), which effectively inhibits platelet secretion and aggregation, does not affect adhesion of a proportion of platelets (10-38%) to collagen (50-100 micrograms/ml). Adhesion is not detectable by changes of light transmission (as measured in the optical aggregometer) and is not affected by inhibitors of cyclooxygenase and lipoxygenase enzymes such as indomethacin and compound BW 755C. This adhesion is independent of the collagen concentration (50-400 micrograms/ml) and the incubation time (5-20 min). This suggests that adhesion to collagen is related to a specific platelet population. Adhesion in the presence of prostacyclin, indomethacin and BW 755C occurs in parallel with the formation of a limited amount of phosphatidic acid. Under those conditions it is also possible to observe some phosphorylation of a 40,000 dalton protein which is a substrate for protein kinase C activity. Phosphorylation of the 20,000 dalton protein, or myosin light chain, is less evident. Chlorpromazine (25-100 micrograms/ml) inhibited the adhesion of platelets to collagen, but propanolol (0.5-4 microM) was inactive. The adhesion of platelets to collagen in these experiments parallels the formation of a fraction of phosphatidic acid and 40,000 dalton protein phosphorylation, which are independent of the increased levels of platelet cyclic-AMP induced by high concentrations of prostacyclin. It is also independent of the formation of cyclooxygenase or lipoxygenase products. PMID- 3085272 TI - Fibrin generation during production of freeze dried antihaemophilic cryoprecipitate. AB - Thrombin activity during separation and cryoprecipitation of CPD-blood was monitored by fibrinopeptide A (FPA) determinations. After pooling and lyophilization of cryoprecipitate, the total amount of contaminating fibrin was estimated by N-terminal amino acid analyses. In addition, retention of fibrin in standard transfusion filters (170 micron) was examined by gamma counting of 125I des-AA fibrin monomer enriched cryoprecipitate prior and subsequent to filtration. Prior to pooling of cryoprecipitate, thrombin activity, as estimated by FPA levels, was most pronounced during collection of blood from the blood donors and during cryoprecipitation and thawing of the plasma bags. Comparison of these FPA concentrations to the total amount of fibrin in pooled, freeze dried cryoprecipitate, as estimated by N-terminal analyses, revealed a considerable generation of fibrin during the process of lyophilization. In freeze dried cryoprecipitate, 5.3 per cent (range 3.0-7.5 per cent) of the fibrinogen had been converted to fibrin, implying a fibrin content of 20.3-60.3 mg per bottle of 500 U factor VIII. The amount of fibrin in two bottles of a commercially available factor VIII concentrate, also containing 500 U of factor VIII, was 14.1 and 19.8 mg, respectively. Sham transfusions of 125I des-AA fibrin monomer enriched cryoprecipitate revealed that only 1.0 per cent (range 0-2.5 per cent) of the fibrin was retained in the standard transfusion filters. Thus, substantial amounts of fibrin may be transfused to patients upon treatment with freeze dried cryoprecipitate. PMID- 3085273 TI - Comparison of the in vivo survival of human factor VIII with and without von Willebrand factor in the hemophilic dog. PMID- 3085274 TI - Quantitative immunoblotting assay of blood coagulation factor XII. AB - The immunoblotting technique was applied to the study of Factor XII (F.XII) in plasma. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of whole plasma followed by electroblotting of the electropherograms to nitrocellulose (NC) membranes and immunologic detection by a double antibody technique was used. 125I-F.XII was transferred to the NC membrane in amounts proportional to the amount applied to the gel provided that a constant amount of carrier protein was present. Based on this, a quantitative assay was developed using either normal plasma or F.XII dilutions in F.XII-deficient plasma as standards. The measurement of F.XII antigen by immunoblotting was reproducible and gave values similar to those obtained by radial immunodiffusion. Two normal plasma pools contained 26 and 29 micrograms/ml of F.XII according to the immunoblotting assay. Compared to other immunoassays, immunoblotting has the advantage of directly estimating the apparent molecular weight (MW) of the protein of interest. Thus, we could confirm the normal apparent MW (80,000) of a F.XII-like molecule previously isolated from a cross reacting material (CRM) positive F.XII-deficient plasma. None of eight CRM-negative F.XII-deficient plasmas showed an 80,000 MW immunoreactive molecule. However, five of these eight plasmas had a faint autoradiographic band at 115,000 MW that was similarly seen in only three out of 43 individual normal plasmas. The nature of this 115,000 MW band remains to be defined. PMID- 3085275 TI - Effects of phalloidin on platelet release. AB - The effect on platelet of phalloidin, a reagent forming phalloidin-actin polymer, was studied. Phalloidin suppressed ATP release but did not affect aggregation after the stimulation with ADP or A23187, although the amount of F-actin was increased by stimulation. The suppression was correlated to the preincubation time and to the concentration of phalloidin. PMID- 3085276 TI - Characterization of various antibodies against tissue plasminogen activator using highly sensitive enzyme immunoassay. AB - Polyclonal and three monoclonal anti-tissue plasminogen activator (a-t-PA) antibodies (1:3 C5, 1:3 G5 and 2:2 B10) were characterized by using enzyme immunoassay (EIA) in which beta-D-galactosidase was coupled to a-t-PA antibody. Monoclonal antibodies called 2:2 B10 and 1:3 G5, specific for both one-chain and two-chain t-PA, strongly bound to one-chain t-PA purified from cultured melanoma cell lines, but 1:3 C5 antibody bound weakly to such t-PA. When polyclonal t-PA antibody was used as the first reaction antibody immobilized on silicone pieces, few determinants were available for monoclonal antibody used in the second reaction due to previous interaction of these determinants in the first reaction. When t-PA levels in the plasma were determined, the presence of EDTA enhanced the sensitivity of t-PA determination by the present EIA technique. Plasma concentrations of t-PA were measured to be higher with 2:2 B10 monoclonal antibody than with polyclonal antibody as the first antibody. Tissue-PA was mainly detected in the endothelial cells, but not in the muscular layer of the inferior mesenteric artery when immunochemical technique was used with polyclonal t-PA antibody. PMID- 3085277 TI - Aspirin and venous occlusion: effects on blood fibrinolytic activity and tissue type plasminogen activator levels. AB - The effects of oral aspirin (650 mg at 18 and 2 hours before testing) on the response to 10 minute venous occlusion in normal young adults (8 men, 4 women) was examined by fibrinolytic methods (euglobulin lysis, and radiofibrin assay of whole blood and plasma activities) and immunoassay of plasma tissue-type plasminogen activator (tPA). Aspirin had no effect on resting (pre-occlusion) values for any of these. Resting plasma tPA levels were approximately 3-fold greater in men than in women, with or without aspirin. Both before and after aspirin, occlusion increased euglobulin lysis activity, plasma fibrinolytic activity, and plasma tPA levels. In addition, there was an occlusion-related increase in cellular phase activity, determined by radiofibrin assay, which was similar, with and without aspirin, to the increase in plasma activity, indicating the participation of blood cells in the response to occlusion. Mean whole blood activity and cellular phase activity (whole blood less plasma activity) were increased 1.8- and 1.5-fold, respectively, by venous occlusion. In all subjects, the net effect of aspirin on occlusion-related increments in fibrinolytic activity were decreases in whole blood and cellular phase responses (p less than 0.05), without significant effects on plasma or euglobulin lysis activity. In contrast, aspirin treatment resulted in a 32% increase in mean individual increments in plasma tPA concentration with occlusion, an effect predominant in men. Aspirin interferes with the cellular phase fibrinolytic response to venous occlusion, and results in increased, rather than decreased, mean occlusion induced increments in levels of plasma tissue activator, determined immunochemically. PMID- 3085279 TI - [Hyperthyroxinemia without hyperthyroidism]. AB - The various causes of persisting hyperthyroxinemia without hyperthyroidism are discussed after short case histories of an infant with hyperthyroxinemia due to TBG excess, discovered by newborn screening for congenital hypothyroidism and a girl with peripheral resistance to thyroid hormones disclosed by investigation of a small goiter. The differentiation of these various causes by thyroid function tests is indicated. Though the anomalies leading to euthyroid hyperthyroxinemia are usually harmless their timely recognition, also in other members of the family, will prevent erroneous diagnosis and treatment of hyperthyroidism. PMID- 3085278 TI - [Familial dysalbuminemic hyperthyroxinemia]. PMID- 3085280 TI - Rhesus immunization after Rh-incompatible kidney transplantation. AB - Rh-immunization of a male recipient was observed following the transplantation of two kidneys from Rh-pos donors. Immunosuppression consisted of azathioprine, prednisone and antilymphocyte globulin (1st transplantation) and cyclosporin A and prednisone (2nd transplantation). The immunization was probably caused by the residual blood in the cadaver kidneys. The use of cyclosporin A might increase the risk of Rh-immunization. PMID- 3085281 TI - The pericyte--a review. PMID- 3085283 TI - Effect of intracerebroventricular injection of vasoactive intestinal polypeptide on systemic blood pressure, and pancreatic and gastric secretions in the rat. AB - In order to examine the central effects of VIP (vasoactive intestinal polypeptide) on systemic blood pressure, and pancreatic and gastric secretions in rats, the peptide was given to rats intracerebroventricularly (i.c.v.) through the lateral cerebroventricle. VIP, when given i.c.v., showed no effects on systemic blood pressure, and pancreatic and gastric secretions in rats. The present results indicate that VIP affects these functions not centrally but peripherally. Physiological role of VIP in the brain remains to be elucidated. PMID- 3085282 TI - Cytoskeletal organization affects cellular responses to cytochalasins: comparison of a normal line and its transformant. AB - The relationships between cytoskeletal network organization and cellular response to cytochalasin D (CD) in a normal rat fibroblast cell line (Hmf-n) and its spontaneous transformant (tHmf-e), with markedly different cytoskeletal phenotypes, were compared (using immunofluorescence, electron microscopy, and DNAse I assay for actin content). Hmf-n have prominent, polar stress fiber (SF) arrays terminating in vinculin adhesion plaques whereas tHmf-e, which are apolar, epithelioid cells with dense plasma membrane-associated actin networks, lack SF and adhesion plaques. Hmf-n exposed to CD become markedly retracted and dendritic, SF-derived actin aggregates form large endoplasmic masses, and discrete tabular aggregates at the distal ends of retraction processes. Prolonged exposure leads to recession of process, cellular rounding, and development of large cystic vacuoles. tHmf-e cells exposed to similar doses of CD display a diagnostically different response; retraction is less drastic, cells retain broad processes containing scattered actin aggregates in discrete foci often associated with plasma membrane, large tabular aggregates are never found and processes persist throughout long exposure, vacuolation is uncommon. The CD-induced microfilamentous aggregates in Hmf-n are composed of short, kinky filament fragments forming a felt-like skein, often aggregates contain a more ordered array of roughly parallel fragments, while those of tHmf-e are very short, kinky, randomly orientated filaments imparting a distinctly granular nature to the mass. Total actin content and the amount of actin associated with detergent-resistant cytoskeletons increase following CD exposure in both cell types. Throughout exposure to CD, the actin-associated contractile proteins tropomyosin, myosin, and alpha-actinin co-localize within the actin aggregates in both cell types. Fodrin, the protein linking cortical actin to membrane, co-localizes with actin aggregates in tHmf-e cells and most, but not all, such aggregates in Hmf-n cells, consistent with their stress fiber derivation. Vinculin is lost from the tabular aggregates at the distal ends of retraction processes in Hmf-n cells concomitant with the fragmentation and contraction of SF. The aborized processes in both cells types contain strikingly similar axial cores of bundled vimentin filaments associated with passively compressed microtubules. The characteristic CD-induced distribution of actin filament aggregates and redistribution of vimentin in these cell types also occur when cells are allowed to respread from the rounded state in the presence of CD. PMID- 3085284 TI - Effects of interleukin-2, OK-432 and interferon-gamma on in vitro induction of nonspecific killer cells by concanavalin A in mice. AB - Human interleukin-2 (IL-2), OK-432 and mouse interferon-gamma (IFN-gamma) were evaluated for their beneficial effects on in vitro induction of nonspecific killer cells by concanavalin A (Con A). Nonspecific killer cells could be induced by culturing C57BL/6 spleen cells for 4 days with Con A. Con A activated killer cells showed direct cell-mediated cytotoxicity (DCMC) and lectin-dependent cell mediated cytotoxicity (LDCC) against natural killer (NK) sensitive YAC-1 cells, and LDCC against NK-resistant EL-4 cells in a 4 hr-51Cr release assay. Higher DCMC and LDCC reactivity against YAC-1 cells, and higher LDCC reactivity against EL-4 cells were obtained with spleen cells cultured with Con A plus IL-2, or Con A plus OK-432 than with those cultured with Con A alone. No beneficial effect of IFN-gamma and no additive effects of IL-2 plus OK-432, or IL-2 plus IFN-gamma were observed in the induction of nonspecific killer cells by Con A. PMID- 3085285 TI - Acute and chronic effects of thyrotropin-releasing hormone (TRH) on stabilogram in spinocerebellar degenerations. AB - A single blind cross over trial was conducted of thyrotropin-releasing hormone treatment in 7 patients with spinocerebellar degenerations. Patients received daily 2 mg of thyrotropin releasing hormone intramuscularly during the 2 week treatment period. Acute beneficial effect on stabilogram was demonstrated, but significant therapeutic efficacy in the chronic treatment failed to be demonstrated, though a trend of effectiveness was observed. PMID- 3085286 TI - Immunosuppression induced by chemicals requiring metabolic activation in mixed cultures of rat hepatocytes and murine splenocytes. AB - Primary cultures of adult rat hepatocytes (Fischer 344) were used as an in vitro metabolic activation system in immunotoxicological assays. Rat hepatocytes were isolated by a collagenase perfusion technique and cultured for 20 to 24 hr to allow the formation of a monolayer on collagen-coated plastic petri dishes. Spleen cells isolated from (C57BL/6 X C3H)F1 mice were cocultured with the hepatocytes along with the chemicals. Cyclophosphamide (CP) and Aflatoxin B1 (AFB1) were effectively activated in this coculture system and produced a dose related suppression of the in vitro antibody responses to LPS, DNP-Ficoll, and SRBC in 3 hr. Neither CP (1 mM) nor AFB1 (10(-4) M) cultured with spleen cells alone produced any effects. Both CP and AFB1 also produced a dose-related suppression of the proliferative responses to LPS, Con A, and PHA. In contrast, up to 100 mM of N-nitrosodimethylamine (DMN) did not suppress any of these assays after a 3-hr incubation in the coculture system. These results indicate that a coculture system can be used to characterize the activity of immunosuppressive chemicals requiring metabolic activation. PMID- 3085287 TI - Effects of butylated hydroxyanisole on acetaminophen hepatotoxicity and glucuronidation in vivo. AB - The present study examined the effects of butylated hydroxyanisole (BHA) on acetaminophen-induced hepatotoxicity and metabolism in vivo with emphasis on possible changes in the glucuronidation pathway. Female Swiss-Webster mice received BHA in the diet (1% w/w) for 12 days (600 to 800 mg/kg/day). BHA prevented acetaminophen hepatotoxicity (600 mg/kg, ip), based on serum alanine and aspartate aminotransferase activities and histopathological examination. The rate of elimination of acetaminophen from blood was 10-fold higher in BHA-fed mice (clearance, 49 ml/min/kg) than in controls (4.4 ml/min/kg). In general, the urinary metabolite excretion patterns in control and BHA-treated mice were the same. However, the rates of acetaminophen conjugation via the sulfation, glucuronidation, and mercapturic acid pathways were enhanced with the rate of glucuronide formation, the major biotransformation pathway of acetaminophen, increased sevenfold in BHA-treated mice (0.041 min-1) compared to controls (0.006 min-1). BHA increased hepatic UDP-glucuronosyltransferase activity twofold, as well as hepatic UDP-glucuronic acid concentrations. In addition, after acetaminophen administration, UDP-glucuronic acid in BHA-treated mice was depleted to a lesser extent and returned to control values more rapidly than in untreated animals. BHA had a similar but less pronounced effect on hepatic glutathione levels. The findings indicate that the rate of acetaminophen glucuronidation is increased in vivo during BHA feeding to mice. This effect appears to play a role in the enhanced excretion of acetaminophen as well as protection against acetaminophen-induced hepatotoxicity. PMID- 3085288 TI - Characterization of a binding protein for the PCB metabolite 4,4' bis(methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl present in bronchoalveolar lavage from healthy smokers and non-smokers. AB - Bronchoalveolar lavage (BAL) was performed in a group of healthy subjects (10 smokers and 10 non-smokers) and the recovered fluid was shown to contain specific binding sites for a metabolite of a polychlorinated biphenyl (PCB), 4,4'-bis ([3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl [(3H-MeSO2)2TCB]. The sites seem to reside within a protein-like component and the apparent dissociation constant (Kd) for the binding was approximately 2 X 10(-7) M regardless of the smoking status of the subject. However, the maximum number of binding sites (Bmax) was significantly lower for the smokers (p less than 0.001). Competition studies indicated that some PCB methyl sulfones had similar affinities for the specific binding sites as (MeSO2)2TCB. Physicochemical characterization of the human (3H-MeSO2)2TCB-binding protein indicated a Stokes radius of 22 A and a sedimentation coefficient of 1.9 S, and on the basis of these parameters an apparent molecular weight of 17,700 was calculated. The binding protein had an apparent pI of 4.9. It is suggested that the specific binding protein for certain PCB methyl sulfones in bronchoalveolar lavage fluid from healthy subjects is responsible for the previously observed tendency of PCB metabolites to accumulate in human lung tissue. PMID- 3085289 TI - Cellular metabolism of lead: a kinetic analysis in cultured osteoclastic bone cells. AB - Detailed characterization of the modulation of lead metabolism in bone is necessary to understand the role of skeletal lead in the expression of clinical and biochemical effects of lead intoxication. The metabolism of lead in osseous tissue is also clinically important because it is the major site of chelation by therapeutic agents, such as CaNa2-EDTA and D-penicillamine. Experiments were conducted to characterize the steady-state kinetic distribution and behavior of 210Pb in osteoclastic bone cells and to identify the biological structures or functions associated with the kinetic pools. Bone cells, derived from mouse calvaria, were enriched for osteoclasts by a sequential collagenase digestion and maintained in primary culture for 1 week. Cultures were labeled with 210Pb as 5 microM lead acetate for 20 hr and the kinetic parameters were obtained by analysis of 210Pb washout curves. Cellular metabolism was defined by three kinetic pools of intracellular lead containing approximately 10% (S1). Approximately 12% (S2), and approximately 78% (S3) of total cellular lead (1.2 nmol/mg cell protein). The halftimes for isotopic exchange were 1, 27, and 480 min, respectively. These data indicate that lead is readily exchangeable from osteoclastic bone cells and, as in soft tissues (hepatocytes), the bulk of cellular lead is associated with mitochondria. PMID- 3085290 TI - Predicting the human teratogenic potential of the anticonvulsant, valproic acid, from a non-human primate model. AB - The anticonvulsant, valproic acid (VPA) is a suspected human teratogen. This study, employing the rhesus monkey as an animal model, demonstrates that VPA has a significant teratogenic potential in the monkey. Timed pregnant monkeys were exposed orally to VPA at approx. 1X, 10X, and 30X (20, 200, and 600 mg/kg/day, respectively) the human therapeutic dose, daily, during organogenesis (gestation days 21-50). All fetuses of mothers exposed to greater than 1X exhibited some form of embryotoxicity. The highest dose, 30X, was 100% embryolethal, while offspring of the 10X dose group exhibited craniofacial and skeletal defects, and low body weights. Maternal pharmacokinetic parameters and plasma metabolites were determined for VPA on the first and last day of dosing for the 10X dose group. Comparison of the kinetic and metabolite data with that obtained for man indicates that the rhesus monkey is a good model for predicting the teratogenic potential of VPA in the human. PMID- 3085291 TI - Effect of toxin from the cyanobacterium Microcystis aeruginosa on ultrastructural morphology and actin polymerization in isolated hepatocytes. AB - Freshly isolated rat hepatocytes incubated with the hepatotoxin from the cyanobacterium Microcystis aeruginosa are rapidly deformed (blebbed). Transmission electron microscopy shows the appearance of unusual intracellular structures and rearrangement of cellular organelles, without any change in the polymerization state of actin. Cytochalasin E (20 microM), a fungal metabolite that causes blebbing of hepatocytes, had no significant effect on the polymerization state of cellular actin, but if Microcystis toxin (10 microM) was added together with cytochalasin E (20 microM), there was a significant increase (from 30% to 44%) in the proportion of unpolymerized G-actin in hepatocytes. These findings are in contrast to the effect of phalloidin (12.5 - 37.5 microM), a peptide hepatotoxin from the poisonous mushroom Amanita phalloides, which also causes blebbing of hepatocytes, and was shown in this study to decrease the level of unpolymerized G-actin in the cells to below measurable levels when added by itself or together with Microcystis toxin or cytochalasin E. PMID- 3085292 TI - Paralytic shellfish poisons produced by the freshwater cyanobacterium Aphanizomenon flos-aquae NH-5. AB - A single filament clonal isolate of Aphanizomenon flos-aquae was made from a water bloom sample taken at a small pond near Durham, New Hampshire, in 1980. When batch cultured the strain was toxic to mice and had an i.p. LD50 of about 5.0 mg/kg. Using an extraction procedure originally designed for paralytic shellfish poisons and other neurotoxins of freshwater cyanobacteria, a purification method was developed. The procedure involved acidified water/ethanol extraction of the cells followed by ultrafiltration, gel filtration, use of C18 cartridges to remove pigments, ion-exchange and high performance liquid chromatography using u.v. detection at 220 or 240 nm. Thin-layer chromatography and high performance liquid chromatography results indicate that Aphanizomenon flos-aquae NH-5 may produce paralytic shellfish poisons, mainly neo-saxitoxin and saxitoxin. Three labile toxins were also detected which were not similar to any of the known paralytic shellfish poisons. PMID- 3085293 TI - Purification of Bacillus anthracis lethal factor by immunosorbent chromatography. AB - Lethal factor from B. anthracis (Vollum 1B strain) has been purified 1130-fold by immunosorbent chromatography using a mouse anti-lethal factor monoclonal antibody Sepharose-4B column. The antibody was covalently attached to CNBr activated Sepharose-4B. Lethal factor bound at pH 7 (0.05 M sodium phosphate buffer) and was eluted with buffer containing 4 M NaSCN with 77% recovery of the immunological activity. Pre-elution with 4 M NaCl was effective in eluting non biospecifically bound proteins. Migration of lethal factor on SDS-polyacrylamide gel electrophoresis indicated a single component (greater than 99% pure) with a molecular weight of 82,000. The effect of a number of dissociation buffers on the antigen-antibody complex has been investigated. Sodium thiocyanate (4 M) in 0.05 M sodium phosphate buffer, pH 7, was the most effective eluting solution, causing complete dissociation of the antigen-antibody complex, while 4M NaI and 4 M NaCl caused 93% and 15% dissociation, respectively. The antigen-antibody complex was found to undergo a reversible dissociation at moderately high pH values. The ionizable group(s) responsible for this dissociation exhibited a pKa value of 9.90. Purified lethal factor exhibited a significant decrease in immunological activity upon freeze-thawing, with 52% loss in potency observed after 3 freeze thaw cycles. PMID- 3085294 TI - Polychlorinated biphenyls produce regional alterations of dopamine metabolism in rat brain. AB - Adult male rats were gavaged with a mixture of polychlorinated biphenyls (PCBs; Aroclors 1254 and 1260) at either 500 or 1000 mg/kg body weight. Concentrations of dopamine (DA) and its major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were determined in caudate nucleus and lateral olfactory tract on postgavage Days 1, 3, 7 and 14. DA and DOPAC concentrations in caudate decreased after exposure to PCBs, as did HVA/DA ratios. DA concentrations in the lateral olfactory tract were unaffected, although DOPAC/DA ratios decreased. These results demonstrate that the mature mammalian nervous system is sensitive to a brief exposure to PCBs and that regional differences exist in the neurochemical sequelae of exposure to PCBs. PMID- 3085295 TI - Abbreviated pretransfusion testing. PMID- 3085296 TI - Rabbit erythrocyte stroma treatment of serum interferes with recognition of delayed hemolytic transfusion reaction. PMID- 3085297 TI - Monoclonal antibody therapy. Anti-idiotypic and non-anti-idiotypic antibodies to OKT3 arising despite intense immunosuppression. AB - The frequency, timing, and specificity of the humoral antibody response to a murine monoclonal antibody (OKT3, IgG2a) were measured in 21 consecutive renal allograft recipients. These patients received i.v. OKT3, 1-5 mg/day for 10-20 days as treatment for acute graft rejection. Maintenance immunosuppression consisted of azathioprine and corticosteroids. Using three different assays, an antibody response was detected in 75% of the 20 patients with adequate samples. The ELISA assay of the overall IgM and IgG reactivity to OKT3 revealed that IgM anti-OKT3 appeared in 65% and IgG anti-OKT3 in 50% of the patients, reaching a peak 20-33 days after the last dose of OKT3. The IgM preceeded the IgG in most cases (P less than 0.02) and in 8 cases was detected during therapy. One patient had high levels of IgM anti-OKT3 before therapy, yet responded normally to OKT3. Interference with the therapeutic effectiveness was evident in one patient who developed IgG antibodies during therapy. His serum blocked the binding of F-OKT3 to normal lymphocytes in the presence of normal BALB/c serum. The blocking assay, done by flow cytometry, measured anti-idiotypic (Id) reactivity since the sera did not affect the binding of OKT8 (another IgG2a) or anti-Leu4 (another anti T3), and the blocking activity remained after affinity absorption with normal mouse IgG. Using this assay, 60% of the patients made an anti-Id response. One made only anti-Id, and several had anti-Id at times when other reactivities were undetectable. Antibodies to non-idiotypic, presumably isotypic, determinants represented on OKT8 occurred in only 44%, while other reactivity (OKT4; IgG2bK) was less common (12%) and weaker. While no adverse allergic reactions occurred in this group of patients, the anti-Id antibodies, which are a prominent feature of the immune response to this and probably other monoclonal antibodies, can block their therapeutic effectiveness and can arise despite intense immunosuppression. This response may require the use of different idiotypes for prolonged or repeated courses of therapy and may be the major obstacle to the use of human monoclonal antibodies. PMID- 3085298 TI - Allospecificity of activated T cells grown from endomyocardial biopsies from heart transplant patients. AB - Studies were conducted to determine the functional characteristics of lymphocytes infiltrating human heart allografts. We have developed methodologies to generate lymphocyte cultures from endomyocardial biopsies. Thirteen biopsies from four heart transplant recipients, obtained at different days during a posttransplant period of less than two months, were cultured in interleukin-2 (IL-2)-containing medium supplemented with irradiated autologous peripheral blood lymphocytes as feeder cells. Lymphocyte cultures were obtained from all 13 biopsies and they exhibited a proliferative response to IL-2, suggesting the presence of activated T cells that express IL-2 receptors. Several cultures consisted of Leu 3 (helper/inducer) T cells, whereas others were primarily Leu 2 (cytotoxic/suppressor) T cells or a mixture of both types of cells. Cultured lymphocytes were also shown to be able to undergo secondary proliferation to donor-specific leukocytes as measured by primed lymphocyte testing (PLT). The PLT specificity of these cells was frequently toward class II HLA antigens of the donor, but certain cultures had PLT specificity associated with class I HLA antigens. These results demonstrate the feasibility of growing functionally active T cells from heart transplant biopsies. An analysis of the phenotypes and allospecificity, as well as a functional characterization of these cells, should generate useful information about the types of T cells involved in cardiac transplant rejection. PMID- 3085299 TI - Skin allograft rejection by L3/T4+ and Lyt-2+ T cell subsets. AB - The L3/T4+ and Lyt-2+ T-cell subsets can be depleted from mice, using selected monoclonal antibodies in vivo, at different times during rejection of, or priming to, allogeneic skin grafts. Although L3/T4+ cells are sufficient to reject skin grafts in naive Lyt-2-depleted mice, we show that Lyt-2+ cells can become involved, after an initial delay, in intact mice. Furthermore, these Lyt-2+ cells are primed to dominate the accelerated rejection of a normal secondary response. Mice depleted of L3/T4+ cells cannot be primed in this way, suggesting that priming of Lyt-2+ cells is dependent on help from L3/T4+ cells. However, in mice depleted of Lyt-2+ cells, priming for rapid rejection can be achieved, presumably via the L3/T4+ population. This suggests that the rejection of skin allografts in a given situation reflects different contributions of multiple effector mechanisms. PMID- 3085300 TI - The influence of the transplantation technique on the duration of endocrine function of pancreas allografts in the rat model. PMID- 3085301 TI - Effect of cyclosporine and low-temperature culture on prevention of rejection of islet xenografts (rat-to-mouse). PMID- 3085303 TI - Effects of high pressure on platelet aggregation in vitro. AB - An apparatus which enables aggregating agents to be added to a stirred suspension of platelets subjected to a pressure of up to 600 ATA is described. The ensuing aggregation reaction is monitored optically. The pressure is applied with helium; data are presented that indicate the effects are mainly attributable to hydrostatic pressure. The aggregation of human platelets induced by ADP was reversibly inhibited by pressure in the 1-270 ATA range. The second phase of aggregation was blocked by 65 ATA; the rate of first phase aggregation was reduced but the time to respond to ADP was not affected. Comparable pressures also affected collagen and arachidonate-induced aggregation. The time to respond to these aggregating agents was prolonged and both the rate and the degree of aggregation were reduced by pressure. PMID- 3085304 TI - Effect of nitroglycerin ointment on penile skin flap survival in hypospadias repair. Experimental and clinical studies. AB - The mobilization of penile neurovascular skin flaps is associated with vasospasm, which may result in ischemic necrosis. A prospective clinical trial of nitroglycerin was performed in 40 children undergoing hypospadias repair. Quantitative fluorescein studies were performed in another group of patients who underwent circumcision. These studies represent the first clinical application of nitroglycerin ointment in human subjects. Our preliminary data suggest that nitroglycerin ointment can enhance survival of skin flaps. PMID- 3085302 TI - [Cytochrome P-450-dependent pathway of oxidation of arachidonic acid and its metabolites]. AB - The experimental data on the role of cytochrome P-450 in the metabolism of arachidonic acid and protanoids in different organs and tissues are analyzed. This system is considered from the standpoint of the possibility to participate in the synthesis of primary prostaglandins. A conclusion is drawn that cytochrome P-450 takes an active part not only in oxidation of different xenobiotics and steroid hormones but also in the synthesis and decomposition of prostaglandins- the most important cell regulators. PMID- 3085305 TI - [Ossification of the auricles as a symptom of congenital disease]. PMID- 3085306 TI - [Destructive diverticula of the small intestine]. AB - The author has made a conclusion that resection of the intestine is the most expedient method of treatment of acute destructive diverticula of the small intestine. PMID- 3085307 TI - [Utilization of urea nitrogen in young calves]. AB - The influence of an increasing intake of urea in feed rations for calves on its levels in blood plasma and urine, development of health condition, weight gains and on other biochemical characteristics in the blood of calves was studied. The experimental group (n = 4) received urea in feed ration from the 17th day of age, at the beginning in the preparation Syrur, later on (from the 66th day) in the synthetic form only. The feed ration of the control group (n = 3) differed only in the zero content of urea. Over the period of ten weeks the blood was sampled for biochemical examination twice a week, since the 52nd day of age urine was also taken at the same intervals. Starting the 24th day of age, the levels of urea in the blood plasma of experimental animals were significantly higher (P less than 0.05). The concentrations of urea in the urine of the animals belonging to the experimental group were also higher, however, the differences in the average values were not significant. In both groups of animals under study no significant differences in the content of vitamin A, concentration of total protein, glucose, bilirubin, activities of aspartate aminotransferase (AST), gammaglutamyl transferase (GMT) and lactate dehydrogenase (LD) were observed. The average daily weight gains were higher in the calves of the control group, however, the differences were not significant. Over the whole experimental period the health condition of both groups of calves was good. PMID- 3085308 TI - [Methemoglobinemia in pigs and the effect of nitrites on the health and growth of piglets]. AB - In 357 pigs of ten age categories fed the commercial feed mixtures the highest methemoglobinemia was found in piglets up to three days of age (3.62%) and the lowest in sows and boars (2.25%). In twelve per cent of animals of the whole set the values of methemoglobin (MHb) reached or exceeded 4%, the maximum was 8.1%, without any clinical symptoms. Except the anemic piglets, these values were not observed in sucking piglets older than three days. Testing of the formation and of the subsequent reduction of methemoglobin in vitro by the action of 14.4 micrograms of sodium nitrite in 1 ml of blood proved no increased disposition to methemoglobinemia in new-born piglets. The levels with 29 to 40% of methemoglobin reached their peaks in all age groups within 50 min. The reconversion was the slowest in adult pigs, the quickest in new-born and weaned piglets; after seven hours the reconversion was almost complete. If recalculated to the initial concentration of hemoglobin, its highest transformation to methemoglobin occurred in older and adult pigs, the lowest in the piglets up to the age of six days and at sideropenic anemia. Short-term administration of sodium nitrite to sows prior to delivery resulted in an increased methemoglobin level in new-born piglets, out o of which 12% were still-born. The repeated administration of sodium nitrite to the sucking piglets (33 to 132 mg per day) influenced neither their health condition nor the body weight gains. The effects of nitrates, nitrites and mechanisms of the reconversion of methemoglobin to hemoglobin are discussed. PMID- 3085309 TI - [The effect of citronellylseneciate on the utilization of feed in sheep]. AB - The influence of citronellylseneciate on the digestibility of nutrients and energy, as well as on the level of some rumen and blood metabolites, was studied in feed rations for rams. Citronellylseneciate was not found to have a significant influence on the digestibility of nutrients and energy and nitrogen balance in feed ration. Neither did citronellylseneciate influence the production of total volatile fatty acids and the molar percent of acetic, propionic and n butyric acids. The addition of citronellylseneciate to feed ration resulted in a decrease in the pH value in rumen and in a non-significant increase in ammonia in rumen and urea in blood. The hematological profile showed increased levels of phosphorus and glutamate-oxalate transferase. PMID- 3085310 TI - [Sexual development and levels of plasma testosterone in the light type of cockerel]. AB - The concentration of testosterone in blood plasma during the ontogenetic development of cockerels was studied in relation to the development of spermatogenic part of gonads. On the basis of the results, sexual development of cockerels can be divided into three stages. The first stage (from hatching to the age of eight to nine weeks) was characterized by a slow increase in gonad weight, by low concentration of plasma testosterone (0.4-2.0 nmol/l) and by the occurrence of spermatogonia in testes. In the course of the second stage (from the age of nine to 16 weeks) a rapid increase in the weight of testes and testosterone concentration was observed. At the end of this stage all phases of spermatogenic cycle were observed in gonads; the testosterone levels averaged to 10 nmol/l. In the course of this stage all cockerels reached sexual maturity; large individual differences in spermatogenesis development were observed. The third stage (16 weeks of age and more) was characterized by an intensive spermatogenesis, further increase in gonad weight and by typical variations of the plasma testosterone levels. The concentration of the circulating testosterone increased before the onset of the final stages of the spermatogenic cycle. PMID- 3085311 TI - [The effect of selected preparations for the protection of draft horses against dipterous blood-sucking insects]. AB - Dipterous blood-sucking insects (horseflies, black flies, gnats, midges) have negative impacts on the performance of draught horses in forest enterprises. For the protection of these animals, the following preparations were applied at the interval of 24 hours: diethyltoluamide, Oxamat (N,N-diethyloxamine acid, USSR) and Stomoxin (synthetic pyrethroid, product of the firm Wellcome, England). In the course of 66 working days, the performance of test animals treated with 10% water emulsion of diethyltoluamide increased by 49.25 cu. m. of skidded wood, i.e. by 0.74 cu. m. wood per horse/day (21.65%), as compared with the control group. The daily savings of prime costs per test horse/day made 16.99 Kcs (Czechoslovak crowns). In comparison with the control group, the performance of horses treated with 5% water emulsion of Oxamat increased by 85.50 cu. m. wood, i.e. by 1.29 cu. m. wood per horse/day (38.00%). Stomoxin at the concentration of 0.05% acted as a good insecticide but had no marked repellent effect. The results of this study document that the production of effective repellents should be introduced in the Czechoslovak Socialist Republic. PMID- 3085312 TI - [Changes in the mineral content of bones in fibrous osteodystrophy in standard minks and Arctic foxes]. AB - Laboratory characteristics of a metabolic disease (Osteodystrophia fibrosa) in standard young minks and arctic foxes is described. In comparison with the control group, while the biochemical characteristics of the blood samples of arctic foxes was not very different from the control group in the contents of macroelements (calcium, phosphorus, magnesium), significant differences were revealed by the analyses of the bone samples of os femoris. In young minks the ash weight in 1 g of fat-free dry matter made only 321.94 mg (52.45%), while in the control group 613.82 mg. A similar decrease (P less than 0.01) was observed, in comparison with the control, in the contents of calcium and phosphorus (44.75% and 56.90%). A slight increase in the magnesium content is not statistically significant. Evaluation of ash content in os femoris in young arctic foxes gave similar results. Biochemical characteristics of their blood showed a significant increase in the activity of alkaline phosphatase. An application of the chemical analyses of bones to diagnosing metabolic disturbances in fur animals is discussed. PMID- 3085313 TI - [Dynamics of selected biochemical indicators of energy metabolism in calves fed 2 different types of milk diets]. AB - The effect of two milk diets on the changes in selected parameters of energy metabolism was studied in calves. After the termination of colostrum feeding, the experimental group of calves (n = 10) was given whole milk whereas the calves in the control group (n = 10) were given the Laktosan milk replacer. Blood was collected for biochemical investigation from the third day of age (determination of glucose concentration) and from the fourth week of age (evaluation of the parameters of lipid metabolism). The plasma concentrations of glucose were about the same in both groups of calves throughout the period of study. The total lipid, total cholesterol and triglyceride levels in blood serum were significantly higher in the calves of the experimental group during the milk feeding period; later they did not differ significantly from the values determined in the control calves. On the other hand, the concentrations of non esterified fatty acids were higher in the calves of the control group in the milk feeding period; the differences, however, are not statistically significant. The average daily weight gains from the 5th to the 18th week of age were significantly higher in the calves given whole milk. PMID- 3085314 TI - [The incidence of coccidia of the genus Cryptosporidium (Cryptosporidiidae) in diarrheal diseases in calves]. AB - In the period from March 1983 to June 1984, the occurrence of Cryptosporidium sp. coccidia in smears of gut contents and samples of excrements stained after Heine (1982) was investigated in calves at the age of 30 days, coming from 16 farms of central Bohemia. The oocysts of Cryptosporidium sp. were diagnosed in 68 calves (occurrence extensity 37.15%) out of the 183 dissected calves with the indication of digestion disorders and in 177 samples of excrements (extensity 33.71%) out of the 525 samples examined. The maximum occurrence of cryptosporidia was recorded in ten- and fourteen-day-old calves (13.9-11.3%); the first findings were reported on the third day of the age of the calves. The intensity of infections induced by cryptosporidia, evaluated as medium-strong, was reported in 33.82% of the dissected calves, in 50% of the samples of excrements of the rearing halls of large cow-houses, and in 36.52% of the samples from large calf-houses. The largest findings of cryptosporidia were associated with the diagnosis of acute catarrhal enteritis (12.02%), catarrhal haemorrhagic enteritis or catarrhal haemorrhagic ileitis (5.46%); however, they were also found when the finding in the digestive tract was negative. Simultaneous bacteriological finding of Escherichia coli and Cryptosporidium sp. occurred at acute catarrhal enteritis (19.12%) and catarrhal haemorrhagic enteritis (11.47%); a simultaneous finding of Salmonella sp. was reported in calves suffering from acute catarrhal enteritis (3.27%). In the calves the occurrence of cryptosporidia was not accompanied by parallel bacteriological findings (4.37%). PMID- 3085315 TI - [Testing the protective effectiveness of avirulent vaccines against trichophytosis in cattle]. AB - The protective action of live avirulent vaccine against bovine trichophytosis, produced by the Bioveta National Corporation at Ivanovice na Hane, was very good and fully comparable with the earlier vaccine produced from the virulent live culture of Trichophyton verrucosum. Experimental challenge with a massive dose of a virulent strain of T. verrucosum produced only minor surface dermal changes in the calves vaccinated with these vaccines, but these changes spontaneously disappeared in a short time. In the control non-vaccinated calves, large and deep lesions were induced by the challenge, spreading to the neighbouring tissues. Compared with both live biopreparations, the protective effect of inactivated vaccine prepared by the irradiation of virulent vaccine with Co60 was much lower. PMID- 3085316 TI - [The effect of Oestrophan Spofa (synthetic analog of prostaglandin F2 alpha) added to the insemination dose on pregnancy and fertility in sows]. AB - Laboratory trials were conducted to study the effect of various concentrations of cloprostenol on the motility and morphological changes of the acrosomes of boar spermatozoa. As found, a cloprostenol concentration of 250 ng per ml of semen to 2500 ng per ml of diluted semen has no adverse effect on the motility of spermatozoa and on the morphological changes of their acrosomes. The concentration of 5000 ng of cloprostenol (in the Oestrophan Spofa product) per 1 ml of diluted semen negatively influences the motility of spermatozoa. An insemination dose of 100 ml of diluted sperm treated with 500 ng of cloprostenol was used for the artificial insemination of 152 sows; 166 sows of the same farm inseminated with untreated semen were used as controls. No gilts were included in the trial. Out of the 152 test sows, 113 conceived after the first insemination, i.e. 74.35%, and the average litter size was 10.04 piglets. In the control group, 125 sows delivered their litters, i.e. 75.30% of the total number, the average litter size being 9.96 piglets. Comparing the reproduction parameters of the experimental and control groups it can be said that the treatment of an insemination dose with 500 ng of cloprostenol immediately before insemination had no influence on the pregnancy rate and on the size of litters. PMID- 3085317 TI - [Physical, chemical and biological study of dust from large-scale pig farms]. AB - Dust deposition in 16 halls of two large pig-fattening farms with dry or wet feeding systems was analyzed. In the halls with wet feeding the samples contained maximally 28 dust particles up to 10 micron and 17 particles up to 5 micron per cm3 of air, in the halls with dry feeding 220 particles smaller than 10 micron and 205 particles smaller than 5 micron per cm3 of air. The total amino acid content in the dust deposition was 17.440 +/- 1.820 g per 100 g of sample and the content of nitrogen compounds (N X X 6.25, %), was 24.170 +/- 2.910. The contents of chemical elements were as follows (mg per kg): zinc 448 +/- 151; manganese 109.9 +/- 49.5; copper 40.5 +/- 12.1; lead 4.77 +/- +/- 4.79; chromium 1.64 +/- 1.47; cadmium 1.61 +/- 1.62; mercury 0.36 +/- 0.39. Chlorinated carbohydrates and triazine and diazine herbicides were present in the following amounts (mg per kg): HCB 0.0023 +/- 0.0021; Lindane 0.0058 +/- 0.0079; DDE 0.0048 +/- +/- 0.0024; DDT 0.0065 +/- 0.0015; Simazine 0.060 +/- 0.020; Atrazine 0.083 +/- 0.059; Prometryn 0.093 +/- 0.040; Chloridazon 0.036 +/- 0.008; Terbutryn 0.085 +/- 0.029. The content of aflatoxin B1 was 12.89 +/- 9.31 micrograms per kg and the maximum amount of polychlorinated biphenyls was 8 mg per kg. Nitrovin was found out only in the dust of two halls: 4.0 and 7.9 mg per kg. The dust deposition also contained 21 genera and species of moulds, six species of mites, numerous saprophytic bacteria and, in some cases, Staphylococcus aureus. For the time being, no viruses have been detected in the dust samples. PMID- 3085318 TI - [A biological method for the determination of mycotoxins--Tetrahymena pyriformis]. AB - The toxic action of selected mycotoxins on a biological subject was tested in the protozoan Tetrahymena pyriformis. The following toxins were tested: toxin T-2 at doses from 1.52 micrograms to 100.0 mg per litre of medium, ochratoxin A at doses from 12.21 micrograms to 800.0 mg per litre of medium, and rubratoxin B at doses from 12.21 micrograms to 800.0 mg per litre of medium. In toxin T-2 the LD100 was found to be about 390.63 micrograms and LD50 about 48.83 micrograms per litre of medium. In ochratoxin A the LD100 was about 25.0 mg and LD50 about 3.13 mg per litre of medium. In rubratoxin B the LD100 was about 200.0 mg and LD50 about 25.0 mg per litre of medium. PMID- 3085319 TI - Identification of serotypes of Haemophilus pleuropneumoniae by counterimmunoelectrophoresis. AB - Counterimmunoelectrophoresis, direct immunofluorescence and immunodiffusion procedures were used to serotype 15 strains of Haemophilus pleuropneumoniae isolated from the respiratory tract of pigs in southern Brazil. Antigens were prepared by extracting cultures with a saline solution or by the phenol-water method. Antisera were prepared in rabbits against serotypes 1, 2, 3 and 5. Thirteen of the isolates were type 5 and two were type 3. No differences were observed between the results obtained in serotyping with counter immunoelectrophoresis and direct immunodiffusion, but both procedures were significantly better than immunodiffusion except with the saline extracted antigen. Counterimmunoelectrophoresis was quicker, more sensitive and more easily performed than the other techniques. PMID- 3085320 TI - Isolation of L monocytogenes from ovine brain. PMID- 3085321 TI - Regulation of ovarian function in the post partum cow: an endocrine model. AB - Recent studies of endocrine function during the period after parturition are discussed and used as a basis for the development of a hypothetical model for the control of ovarian function in the cow after calving. It is postulated that the main sequence of endocrine changes is as follows. At first gonadotrophin releasing hormone is secreted infrequently in small quantities. Very early after parturition the secretion of follicle stimulating hormone increases, thus stimulating the development of follicles. There is then a gradual increase in responsiveness to gonadotrophin releasing hormone which results in an increased frequency of release of pulses of luteinising hormone. Follicular growth results in the production of oestradiol and inhibin. Finally there is a gradual restoration of the positive feedback mechanism by which preovulatory gonadotrophin release occurs. In a normal cow the whole process appears to be complete by approximately two weeks after parturition. PMID- 3085322 TI - Rapid quantitative assessment of the distribution of Listeria in silage implicated in a suspected outbreak of listeriosis in calves. AB - A silage clamp was sampled for the presence of Listeria species. Even though covered by a heavy duty black plastic sheet the top few centimetres of silage were heavily contaminated with Listeria species. In the areas nearest the edges of the sheet the pathogenic species Listeria monocytogenes was found in numbers in excess of 12,000 organisms/g silage. Using the methods of isolation described, pathogenic species of Listeria could be differentiated from non-pathogenic species in three to four days. PMID- 3085324 TI - Induction of immunity against infection with Theileria parva (East Coast fever) in cattle using plasma membranes from parasitized lymphoblasts. AB - Protection against challenge with Theileria parva was conferred on three of four calves given three or four inocula of plasma membranes prepared from 6 to 12 X 10(8) autologous parasitized lymphoblasts from cultured cell lines. In contrast, calves remained susceptible to infection following immunization with membranes prepared from allogeneic parasitized lymphoblasts. Similarly, calves vaccinated with either gamma-irradiated autologous or allogeneic infected cells also died of East Coast fever after challenge. The results raise the possibility of vaccination against T. parva using subcellular material from infected lymphoblasts. PMID- 3085323 TI - Epidemiology of theileriosis in calves in an endemic area of Kenya. AB - Thirty-one calves born into five Maasai zebu cattle herds over a period of 1 month in the Trans-Mara Division of Kenya, endemic for theileriosis, were recruited for an intensive study of theileriosis. No calves up to 6 months of age died but all developed Theileria infections as judged by slide examination and serology. Parasitosis by T. mutans schizonts in lymph node smears was usually higher than that of T. parva. The T. mutans schizonts usually occurred at an earlier age but persisted at a patent level for a shorter time than those of T. parva. Serological findings using the indirect fluorescent antibody test confirmed the parasitological findings. It was evident that colostral transfer of Theileria antibodies was frequent. Theileria piroplasm parasitaemia had developed in all calves by 111 days of age. The earlier parasitosis by T. mutans reflected the higher infection rates in Amblyomma spp. than in Rhipicephalus appendiculatus. The mean number of R. appendiculatus on the ears of calves during the observations was 9.1 adults and 1.5 nymphs. Clinical episodes of T. mutans and T. parva infection were associated with febrile responses, enlarged lymph nodes, anaemia and other symptoms and about 80% of calves had poor weight gains or weight losses during either clinical infection. It would appear that theileriosis is one of the most important factors in the stunting of calf development in the area. PMID- 3085325 TI - Effects of heating and freezing on the viability of sarcocysts of Sarcocystis levinei from cardiac tissues of buffaloes. AB - Dogs fed buffalo heart muscle containing sarcocysts of Sarcosystis levinei and heated at 65-75 degrees C did not shed sporocysts, whereas other dogs fed infected heart muscle heated between 40 and 60 degrees C shed sporocysts. Dogs fed infected heart muscle stored at -4 degrees C for 48 h did not shed sporocysts, but those fed similar infected tissues stored at -2 degrees C for 24 h shed sporocysts. The results indicate that sarcocysts of S. levinei are rendered noninfective by heating to 65 degrees C or by freezing at -4 degrees C. PMID- 3085326 TI - Time course of arterial repair following endothelial denudation in the rat carotid artery. A morphometric study in Wistar and Sprague-Dawley rats. AB - Repair processes in the intima and media of the rat carotid artery were studied morphometrically for time intervals of up to 28 days after injury induced by air drying. Air-drying injury included endothelial denudation as well as medial necrosis. Repair was most rapid between days 9 and 11 after injury as regards the increase in myointimal lesion size, the extent of repopulation of the media and re-endothelialization. After day 11, myointimal lesion size continued to increase until day 28. Medial repair, however, almost completely ceased at day 11, 25% of the inner media and 5% of the outer media remaining necrotic. At day 21, the vessels were almost completely re-endothelialized; however, even at day 28, about 10% of the middle of the vessel was still permeable to Evans Blue. The response of Sprague Dawley rats to injury differed from that of Wistar rats. Compared with Wistar rats, Sprague Dawley rats showed larger myointimal lesions, less medial necrosis and slower endothelial repair. It is suggested that the extent of medial necrosis and the speed of endothelial regeneration affect the arteriosclerotic response in rats. PMID- 3085327 TI - Changes of the elastin compartment in the human meniscus. AB - We report on the elastin, collagen and ground substance compartments in the human meniscus and their interrelationships. Elastin is found in neonates and shows both an arrangement parallel to the collagen fibre and into net-like structures. Branching, caliber inconstancy, rupture and the phenomenon of the "rubber band" are findings within the different forms of the meniscopathy. The function of the elastin compartment cannot be visualised without suggesting "puncta fixa". The morphology of the collagen-elastin-junctions has been described and their possible mode of function is discussed with the help of a model. PMID- 3085328 TI - Epithelial inclusions and Tamm-Horsfall protein in paranephric lymph nodes. A light microscopy and immunocytochemical study. AB - An unusual histological pattern made up of tubular structures and clusters of apparently epithelial cells floating within sinusoidal deposits of Tamm-Horsfall (TH) protein was observed in several lymph nodes removed with renal tumours (3 Wilms' tumours, 1 cystic nephroma) and pathological but non neoplastic kidneys (2 cases of reflux nephropathy). Masses of TH protein, often containing desquamated tubular epithelial cells, were also found in tubules, interstitium and perivascular lymphatic vessels of the resected kidneys, but never in the tumour tissue. Lymph nodes draining renal tumours, although moderately enlarged because of reactive hyperplasia and TH protein deposits, did not contain metastases. Our findings suggest that these inclusions originate from renal tubular epithelium and are transported to paranephric lymph nodes along with TH protein. PMID- 3085329 TI - Fatal mitochondrial cardiomyopathy in Kearns-Sayre syndrome. AB - The clinical and postmortem findings in a 26 year old man with Kearns-Sayre syndrome are described. In the last years of his life he suffered from cardiac arrhythmias and a congestive cardiomyopathy, dying of cardiac pump failure. The heart was enlarged, especially the left ventricle which was fibrotic and excessively dilated. Histological and fine structural investigation revealed an excessive loss of myofibrils and an increase of enlarged mitochondria with lamellar and atypically tubular cristae in widespread heart muscle cells. Mitochondrial anomalies were also observed in some cells of the conductive system. This patient thus suffered not only from a mitochondrial myopathy with ragged red fibers but also from a fatal mitochondrial cardiomyopathy. The anomalies observed in the mitochondria of the conductive system cells suggest that the well-known conductive abnormalities in patients with Kearns-Sayre syndrome might be at least partly caused by disturbed function of these mitochondria. PMID- 3085330 TI - Evidence for proximal tubular cell origin of a sarcomatoid variant of human renal cell carcinoma. AB - A pure sarcomatoid variant of renal cell carcinoma obtained from a hydronephrotic kidney of an elderly white female was grown in tissue culture. Two parallel cell lines, one from the primary neoplasm and the other from a seeded metastasis within the same kidney have been cultured for more than 60 passages over a period of three years. Structural and functional studies of this neoplasm confirmed that it originated from proximal tubular cells. PMID- 3085331 TI - Enzyme- and immunohistochemical study of a case of histiocytic necrotizing lymphadenitis. AB - A combined morphological, immunohistological, and enzyme histochemical analysis was performed on frozen and fixed lymph node tissue in a case of histiocytic necrotizing lymphadenitis (HNL) using conventional histology, a panel of monoclonal and polyclonal antibodies, and a series of common haematological enzyme reactions. Histology showed multiple paracortical necrotizing foci which, in a prominently necrobiotic background devoid of granulocytes, contained large numbers of foamy histiocytes and macrophages intermingled with cells resembling degenerating plasmacytoid T-cells. Most of the histiocytes were alpha1 antichymotrypsin positive and foamy cells were also distinctly Leu-M1 positive. Strong granular acid phosphatase (AP) positivity was present in the cytoplasm of the macrophages and histiocytes. The cells with plasmacytoid features showed weaker and homogeneously diffuse AP staining. Alpha-naphthyl acetate esterase (ANAE) activity was much less striking than AP in the necrotizing foci and most of the ANAE negative cells corresponded to those with plasmacytoid features. No cells with B-cell lineage markers were present within the necrotizing foci; most of the occasional T-cells (Leu-1+, Leu-4+) present in the foci were Leu-2a+ (OKT8+) whereas OKT10+ lymphoid cells were abundant and appeared to correspond with the cells with plasmacytoid features. Our combined data confirm that the special type of necrosis found in HNL develops within foci of plasmacytoid T cells undergoing regressive changes and apparently exhibiting distinct immunohistological and enzyme histochemical features. PMID- 3085332 TI - Diagnosis of the type of amyloid in paraffin wax embedded tissue sections using antisera against human and animal amyloid proteins. AB - Different histochemical techniques were compared on paraffin wax embedded tissue sections for routine classification of amyloid; the following methods were used: potassium permanganate, the indirect immunoperoxidase method using polyclonal anti-human amyloid antisera (anti-AA, anti-A lambda, anti-A kappa and anti-AF) and the peroxidase-antiperoxidase (PAP) method using antisera against human, bovine, hamster and canine AA amyloid. Anti-human AA antiserum appeared to be a useful tool in this respect. Polyclonal anti-AL antisera may be helpful in diagnosing AL amyloid, but were less of value than anti-AA serum. Strong cross reactivity between anti-bovine AA antiserum and human AA amyloid deposits was found. This indicates that animal amyloid AA antisera can also be used for the diagnosis of AA amyloid in human tissues. PMID- 3085333 TI - Preliminary investigations of a correlation between electron energy loss and morphometric analyses on ultrathin cryosections from normal and neoplastic gastric tissues. AB - Electron energy loss spectroscopy (EELS) has been used to measure the ratios of C, N, O, P and Ca in ultrathin cryosections from normal and neoplastic gastric tissues. First results show a correlation between the EELS, and morphometric data in cells from these tissues. We have found that ultrathin, freeze-dried cryosections, with an average thickness of up to 75 nm, are stable enough for EELS-analysis in a 200 KV electron microscope with an adapted Gatan-EELS Spectrometer. PMID- 3085335 TI - Morphometric analysis of small intestinal mucosa. III. The quantitation of crypt epithelial volumes and lymphoid cell infiltrates, with reference to celiac sprue mucosae. AB - With the aid of computerised image-analysis, morphometric techniques were used to measure the volumes of crypt epithelium, with reference to a constant test area (10(4) microns2) of muscularis mucosae, in untreated and treated celiac sprue mucosae in comparison with four other groups of control jejunal specimens. Crypt epithelial lymphocyte populations were also analyzed in terms of absolute numbers (N), mean nuclear (DN) and cytoplasmic (DCYT) diameters, and mean nuclear (VN) and cell (VCELL) volumes. Untreated celiac sprue crypts, despite a 3-5 fold increase in volume over control mucosae, contained a markedly expanded population of lymphocytes which was localised predominantly to the upper crypt regions and comprised approximately 6% large lymphocytes (DN greater than 6 microns: DCYT greater than 9 micron). These changes were entirely reversed by dietary treatment and hence were considered to be gluten-driven. The infiltrate might reflect the expression of gluten receptors on maturing upper crypt enterocytes: but why these lymphocytes do not cause any apparent injury to crypt epithelium (unlike surface epithelium) or influence its well-known compensatory response, remains unclear. PMID- 3085334 TI - The gastric juice aspiration syndrome (Mendelson syndrome). Aspects of pathogenesis and treatment in the pig. AB - The gastric juice aspiration syndrome (GJA-S, Mendelson syndrome) was studied experimentally in pigs. Following instillation of gastric juice into the right main bronchus necrosis of pneumocytes and bronchiolar epithelium occurred with activation of complement and a prostaglandin E releasing system (possibly the kinin system). Cell necrosis was followed by loss of surfactant and formation of hyaline membranes, rich in immunoglobulin M. The alveolar damage organized, resulting in intraalveolar and interstitial fibrosis. The causative agents were found to be both gastric hydrochloric acid and pepsin. Pretreatment with H2-, or acetylcholine-receptor-antagonists (cimetidine or pirenzepin) as well as buffering of the gastric juice to a neutral pH did not prevent lung fibrosis. If a mixture of aluminium hydroxide, magnesium carbonate and oxethazaine was added to the aspirate, development of lung fibrosis was prevented, but severe granulomatous reaction with foreign body giant cells within both lungs evolved. Kallikrein inhibitor, when administered intravenously not later than 3 min after artificial aspiration, protected the left lung completely and large areas of the right. If infused within 60-90 s complete protection of the left lung and the right upper lobe was achieved. In the majority of the animals a mild focal fibrosis developed in the right lower lobe; in one experiment both lungs were devoid of fibrotic areas. If Kallikrein inhibitor was infused 5 min prior to aspiration, lung fibrosis was not prevented. PMID- 3085336 TI - Lipofuscin accumulation in the human spleen with an unusual distribution. A case report. AB - Lipofuscin granules were found in an unusual distribution in an atrophic human spleen. The pigment was confined to the sinus littoral cells and was absent from the splenic histiocytes. The lipofuscin differed from the ceroid-type of lipofuscin found in the various conditions associated with the 'syndrome of the sea-blue histiocyte' in its distribution, ultrastructure and its association with splenic atrophy rather than splenomegaly. PMID- 3085337 TI - Kaposi's sarcoma. Origin and significance of lymphaticovenous connections. AB - Review of histopathological material in nine autopsies and 35 skin biopsy specimens of Kaposi's sarcoma in male homosexuals suggested that aberrant lymphaticovenous connections occur in the earliest stage of the Kaposi lesion. Venular glomeruloid structures in the dermis and their analogous radial venolymphatic channels in medium-sized and larger veins signified coupling of the lymphatic and venous systems, a characteristic previously noted in angiographic studies and considered to be unique in Kaposi's sarcoma. Lymphatic channels penetrated veins selectively rather than arteries, particularly in deep fat, liver, gastrointestinal submucosa and the hilum of lymph nodes. The initiation of the Kaposi lesion thus may be an abnormal recapitulation of the coupling of venous and lymphatic systems which occurs during embryonic growth. A chronological staging scheme is used which proposes lymphaticovenous union as the initial morphological differentiating event. The precise origin of the characteristic spindle cells in the developing lesion remains unclear, although convergent differentiation of lymphatic and blood vascular endothelium may be considered. Alteration of the microcirculation, particularly that distal to the capillary bed, may explain several of the histopathological and haemodynamic features of Kaposi's sarcoma, including lesional thrombosis and infarction, tissue haemorrhage, vascular dilatation, cavernous pseudoangiomas and acute right sided heart failure. PMID- 3085338 TI - Glomerular lesions associated with the Crow-Fukase syndrome. AB - Three cases of the Crow-Fukase syndrome without radiographic changes of multiple myeloma are reported, with special reference to the glomerular changes seen. Proteinuria was detected in one case, although decreased renal function was observed in all (GFR: 41.0, 62.0, 74.1 ml/min respectively) at the time of renal biopsy. Glomerular changes were similar in all three cases. The main characteristic changes were mesangial proliferation and thickening of the glomerular capillary walls. Pictures by light microscopy were therefore similar to that of MPGN. On electron microscopy, the thickened capillary walls showed circumferential mesangial interposition and the subendothelial zone was electron lucent and contained small dense granules or flocculent deposits. By immunofluorescent microscopy, no immunoglobulins, complement components or light chain were detected in the glomeruli except in one case. PMID- 3085339 TI - Immunolocalization of type III collagen and procollagen in cirrhotic human liver using monoclonal antibodies. AB - Immunolocalization of type III collagen and procollagen in cirrhotic human liver was studied using monoclonal antibody specific for the helical determinant of type III collagen extracted from human placenta. Deparaffinized, trypsin-treated cirrhotic liver sections from 8 autopsy cases were examined by the unlabeled peroxidase-antiperoxidase and immunofluorescence techniques. These techniques revealed the localization of this epitope shared by type III collagen and procollagen not only in the extracellular matrix of hepatocytes and sinusoidal cells but also in the cytoplasm. In hepatocellular carcinoma concurrent with cirrhosis, neoplastic cells were shown to react with this antibody as well. These results are consistent with data obtained using antiserum specific for bovine type III procollagen aminopeptide which appeared in our previous report. PMID- 3085340 TI - Malignant melanoma--its precursors and its topography of proliferation. DNA Feulgen-cytophotometry and mitosis index. AB - DNA-content and size of the nuclear areas in different zones of malignant melanomas of different histological types and in dysplastic naevi were measured in order to provide information on the histogenesis and proliferative behaviour of human malignant melanoma. The results were compared with those from normal epidermis, common naevi, and reactive melanocytic hyperplasias. The mitotic index of melanomas--divided into different topographic zones in an analogous way--was also determined. The DNA-histographs of all naevi and reactive melanocytic hyperplasias showed a diploid maximum, but the dysplastic naevi had a larger proportion of nuclei with hyperdiploid and tetraploid DNA-content, indicating an increased proliferative activity. The mean values (X) of nuclear areas in dysplastic naevi (DN) were about the same as in common naevi (CN) and slightly lower than in superficial spreading melanomas (SSM). The coefficient of variability (cv) as an indicator of anisokaryosis was markedly higher in DN (27.8) and SSM (29.3) than in CN (20.2). In DNA-content we found similar results: almost no difference in mean values, but DN taking an intermediate position between CN and SSM with respect to cv (CN: 12.3; DN: 21.0; SSM: 36.6). There was no unequivocal evidence in these data for DN being a precancerous stage. Superficial melanomas with a nodular component ("SSM/NM") differed from SSM and NM by increased DNA-content and greater variability of nuclear areas and showed the clearest features of malignancy in their DNA-histographs. The mitotic indices had rather low values in SSM and intraepidermal marginal zones of "SSM/NM" on one hand and markedly higher values in NM and nodular parts of "SSM/NM" on the other. The highest mitotic counts were found in the three investigated metastases. PMID- 3085341 TI - Histotopographic evidence that amyloid deposits in sclerocalcific heart valves and other chronic lesions of the cardiovascular system are related to old thrombotic material. AB - Deposition of amyloid in human sclero-calcific heart valves has been reported recently as a localized age-independent and dystrophic form of amyloidosis. Histochemical studies have shown that the deposits are permanganate resistant, contain tryptophan and P component and are immunologically unrelated to any known type of amyloid fibril protein. In this study histological observations from a series of four selected sclerotic heart valves show amyloid deposition in old thrombotic material covering fusing commissures or appositional collagen on the body of the leaflets. Similar cases from extravalvular sites have been added to the series: a partly hyalinized thrombus of the left atrium, a thrombotic aneurysm of the left ventricle, 2 thrombotic atherosclerotic aneurysms of the aorta and popliteal artery respectively, and an encapsulated haematoma of the scalp. The deposits are Congo red positive with typical green dichroism in polarized light, permanganate resistant and contain tryptophan. Electron microscopy of 3 cases displays small fibrils which are typical of amyloid. No patient showed evidence of systemic amyloidosis. The natural history of sclero calcific valvulopathies and present observations favour the following pathogenesis: first, recurrent thrombotic deposition on thickened and fibrotic endocardium; second, degradation of a coagulation-related protein with beta potential during the aging of the clot with transformation into amyloid fibrils; finally, inclusion of the amyloid in sclerotic replacement tissue. PMID- 3085343 TI - [Selection of appropriate ribonuclease inhibitors in the study of polysomes in human lymphocytes]. AB - Polysome profiles are described for lymphocytes of donor peripheral blood treated with various inhibitors of RNAases. The most effective inhibitor was diethyl pyrocarbonate, which enabled to maintain high content of polysomes (up to 70%) in these cells. Ribosomes, treated with diethyl pyrocarbonate, exhibited functional activity in the puromycin test. A natural inhibitor of RNAases from liver tissue inhibited incompletely the enzymatic activity in lymphocytes. Heparin proved to be an inadequate inhibitor of RNAases in all the cells of lymphoid origin (lymphocytes from peripheral blood of donors and of the patients with chronic lympholeukosis, lymphocytes isolated from adenoids and spleen tissue); it induced disaggregation of polysomes and dissociation of ribosomes. PMID- 3085342 TI - Primary mediastinal clear cell lymphoma of B-cell type. AB - This is a report on 8 mediastinal tumours that occurred in young adults (19-43 years, mean: 29.4); predominantly in females (6/8). Initial symptoms consisted of thoracic pain and venectasia and in only one case in B symptoms. After surgical tumour reduction, radiation and/or chemotherapy, local recurrence was observed in each case under clinical care; abdominal spread is presently suspected in 3 patients; 3 died 11, 13 and 22 months after diagnosis. None developed leukaemia. The tumours are B-cell neoplasms with a characteristic immunophenotype: leucocyte common antigen+, common acute lymphoblastic leukaemia antigen-, B 1-antigen+, surface and cytoplasmic immunoglobulin-. Flow cytometry revealed DNA-diploidy in 7 cases and a moderately (3.2-3.8%) to extremely high (8.0-20.6%) S-phase component. The proliferation associated antigen Ki67 was detectable in 10-60% of the tumour cell nuclei, thus stressing the considerable or rapid growth. Histopathology is characterized by a diffuse growth pattern and a clearness and abundance of cytoplasm of the pleomorphic tumour cells, which vary in size and nuclear morphology from patient to patient. Apoptoses are more numerous than mitoses. Fibrosis and focal necrosis are common, sclerosis is present in 3 cases. We suggest that primary mediastinal lymphoma of B cell type is a novel B-lymphoma variant. PMID- 3085344 TI - [Locus differentiation of hereditary mucopolysaccharidoses]. AB - Locus differentiation of hereditary mucopolysaccharidoses (MPS) was carried out using the methods of enzymodiagnosis and metabolic cooperation. MPS loci were differentiated in 66 patients from 58 families, examined in the Centre of Medical Genetics, as well as in 21 patient from 12 families, found in Uzbek and Turkmen populations. The following MPS types were detected: MPS I H, MPS I H/Sh, MPS II, MPS III A and B, MPSIV A and B, MPS VI. Among the patients examined MPC II was the most widespread type of the disease. Ethnic dissimilarity was noted in the MPS distribution over the USSR regions. PMID- 3085345 TI - [Metabolism of essential fatty acids and prostaglandins in the rat liver in chronic alcoholic intoxication]. AB - Patterns of essential fatty acids and of prostaglandins metabolism were studied in liver tissue of rats which consumed 5% solution of ethanol as a single source of drinking material within 3, 6 and 9 months. Deficiency of essential fatty acids and a decrease in the content of prostaglandins occurred during development of chronic alcohol intoxication. Activity of PGE2 synthetase was decreased within 3 and 9 months and the activity of PGF2 alpha synthetase--within 9 months of the experiment. Activity of linoleyl-CoA-desaturase was decreased similarly in all the systems studied. The decrease in prostaglandins content found in liver tissue after long-term consumption of ethanol was due both to a deterioration in accessibility of the substrate for prostaglandin synthetase and to the decrease in activity of prostaglandin synthetases. PMID- 3085346 TI - [Nitrogen and fat balance of premature infants in the 1st days of life]. AB - Significant nitrogen imbalance was recorded in the presence of satisfactory fat retention in premature infants during the first days of life. It is suggested that along with the biochemically immature processes of protein assimilation aggravated by the perinatal pathology protein deficiency plays an important role in the nitrogen imbalance in the premature infants. To prevent the above disorders the authors recommend that the premature infants be given minimum 1.8-2 g protein/kg bw; long-term milk infusions through a naso-gastric tube could be helpful in this case. PMID- 3085349 TI - [Duodenal diverticula]. PMID- 3085348 TI - [Effect of a fat emulsion on the free amino acid content in the blood when administered enterally together with amino acids]. AB - The influence of an intralipid fatty emulsion on the absorbability of polyamine amino acid mixtures was studied during their administration through a tube into the duodenum of white rats. Polyamine was administered in a dose of 0.25 g of nominal protein, intralipid in a dose of 0.2 g of fat/g bw/day. It was found that polyamine administered into the small intestine was intensely absorbed during the first two hours which was evidence by an increased content of amino acids in the blood. Intralipid used simultaneously with polyamine intensified the absorption of the latter. Preliminary administration of intralipid promoted a more rapid polyamine absorption, especially of side branch chain amino acids. The results obtained have presented an experimental validation of using nitrous compounds after preliminary administration of fatty emulsions in enteral tube feeding. PMID- 3085347 TI - [Lipid peroxidation intensity in the liver in protein-energy deficiency]. AB - A fall in the glutathione peroxidase, glutathione reductase activity and selenium concentration was recorded in the liver of rats given diets poor in protein. The hepatic antioxidizing activity was lowered, lipid peroxidation (LPO) was intensified which was expressed in the growth of the amount of conjugated dienes, diene ketones and malonic dialdehydes. Diets poor in protein supplemented with sodium selenite and alpha-tocopherol acetate induced a significant increase in the selenium concentration and intensified the hepatic glutathione peroxidase and glutathione reductase activity. The rise in the oxide reductase activity was attended by a decreased rate of accumulation of LPO products, their amount being significantly lower as compared to that in the animals who were not given antioxidants. PMID- 3085350 TI - [Combined small and large intestine diverticulosis complicated by hemorrhage]. PMID- 3085351 TI - [Dynamics of the changes in the plasma amino acids of acute pancreatitis patients on parenteral feeding using different nitrogen preparations]. PMID- 3085352 TI - [Effect of butadione on lipid metabolism in chronic ischemic heart disease patients]. PMID- 3085353 TI - Anticipating and evaluating the collaborative research process. PMID- 3085354 TI - [Parasites of Periplaneta americana (L.) grown in laboratories]. PMID- 3085355 TI - Effect of Piriprost, a 5-lipoxygenase inhibitor, on leukocyte accumulation during thioglycollate-induced acute inflammation. AB - We evaluated the effect of a prototype 5-lipoxygenase enzyme inhibitor, Piriprost [6,9-deepoxy-6,9-(phenylimino-)delta 6,8-prostaglandin I1], on the leukocyte accumulation induced by intraperitoneal injection of thioglycollate in rats. Piriprost, at 40 mg/kg, i.p., inhibited leukocyte accumulation by 34 +/- 12% (mean +/- S.D., n = 9). With experimental groups containing small numbers of rats (6 to 9) inhibition was statistically significant in 7 of 9 cases. Piriprost shared this property with dexamethasone; however, dexamethasone at 5 mg/kg, p.o., inhibited leukocyte accumulation to a greater extent, 61 +/- 6% (mean +/- S.D., n = 5) and the inhibition was statistically significant in 5 of 5 cases. Conventional non-steroidal antiinflammatory agents including aspirin and phenylbutazone were ineffective in our model. Our results suggest that certain compounds that inhibit the 5-lipoxygenase enzyme, without inhibiting the cyclooxygenase enzyme, can reduce the leukocyte accumulation associated with acute inflammation. PMID- 3085356 TI - Effect of the beta-2 adrenergic agonist fenoterol on the release of leukotrienes and prostaglandin D2 from human lung parenchyma. AB - Ca++-ionophore and antigen challenge of human lung fragments caused a massive release of leukotrienes, whose relative proportions varied considerably and were dependent on the experimental conditions. A broncho-selective beta 2-adrenoceptor agonist fenoterol was able to prevent the antigen-induced leukotriene release completely, whereas the Ca++-ionophore induced leukotriene release was only moderately inhibited. The HPLC data were confirmed by SRS-A bioassay. PMID- 3085357 TI - Dementia in later life: research and action. Report of a WHO Scientific Group on senile dementia. PMID- 3085358 TI - Young people's health--a challenge for society. Report of a WHO Study Group on young people and "Health for All by the Year 2000". PMID- 3085359 TI - Community prevention and control of cardiovascular diseases. Report of a WHO Expert Committee. PMID- 3085361 TI - The cost-effectiveness of early or delayed surgery in acute cholecystitis. PMID- 3085360 TI - Repair of chronic radiation wounds of the pelvis. PMID- 3085362 TI - Lactase deficiency and lactose malabsorption. A review. AB - The results of previous investigations of lactase deficiency and lactose malabsorption are reviewed. It showed that lactase activity and its decline in animals and humans is controlled genetically, but also that its phenotypic expression as lactose malabsorption is influenced by nongenetic factors: adaptation, biological (circadian) rhythmicity, hormones, gastrointestinal functions, and nutritional components can alter the response to lactose intake. PMID- 3085363 TI - [Dose comparative study with ranitidine in the therapy and prevention of duodenal ulcer]. AB - The clinical value of ranitidine, 75 b. d. versus 175 mg b. d. in 48 patients with endoscopically proven duodenal ulcer was evaluated in a randomised double blind study. In the two groups of patients there was no significant difference of ulcer healing. After 4 weeks of treatment in each group healing of 79% and after 6 weeks of 92% of the ulcers was observed. After 8 weeks the healing rate was 96% in patients who received 75 mg b. d. and 100% in those receiving 150 mg of ranitidine b. d. Smoking prolonged ulcer healing in both groups. Upon ulcer healing in 34 patients a ranitidine dosis of 75 mg nocte for prophylaxis of ulcer recurrence was compared with a 150 mg dosis nocte. Within 12 months in the two groups recurrence of duodenal ulcer was found by endoscopy in 21% and 20% of the patients. 7 out of 8 patients with ulcer recurrence were smokers. According to the results of these studies it appears that the recommended standard dosis of ranitidine for treatment of duodenal ulcer could be reduced by one half. To confirm our conclusions, further studies with a greater number of duodenal ulcer cases are necessary. PMID- 3085364 TI - [Effect of CO2 concentration on the measurement of O2 concentration in respiratory gases using analyzers employing the thermomagnetic principle]. PMID- 3085366 TI - Ciliates as possible food source for adult Oxyuris equi Schrank 1788. PMID- 3085365 TI - Interaction of Trypanosoma cruzi with macrophages: effect of previous incubation of the parasites or the host cells with lectins. AB - The effect of incubation with lectins of the macrophages or two evolutive stages of Trypanosoma cruzi (noninfective epimastigotes and infective trypomastigotes) on the ingestion of the parasites by mouse peritoneal macrophages was studied. Lectins which bind to residues of mannose (Lens culinaris, LCA), N-acetyl-D glucosamine or N-acetylneuraminic acid (Triticum vulgaris, WGA), beta-D-galactose (Ricinus communis, RCA), N-acetyl-D-galactosamine (Phaseolus vulgaris, PHA; Dolichos biflorus, DBA; and Wistaria floribunda, WFA), fucose (Lotus tetragonolobus, LTA), and N-acetylneuraminic acid (Limulus polyphemus, LPA) were used. By lectin blockage we concluded that, alpha-D-mannose-like, beta-D galactose and N-acetyl-D-galactosamine (PHA, reagent) residues, located on the macrophage's surface are required for both epi- and trypomastigote uptake, while N-acetylneuraminic acid and fucose residues, impede trypomastigote ingestion but do not interfere with epimastigote interiorization. Macrophages' N-acetyl-D glucosamine residues are required for epimastigote uptake. On the other hand, from the T. cruzi surface, mannose residues prevent ingestion of epi- and trypomastigotes. Galactose residues participate in endocytosis of trypomastigotes, but hinder epimastigote interiorization. Exposed N-acetyl-D glucosamine residues are required for uptake of the two evolutive forms. N acetylneuraminic acid residues on the trypomastigote membrane prevent their endocytosis by macrophages. These results together with those reported previously showing the effect of monosaccharides on the T. cruzi-macrophage interaction, indicate that (a) sugar residues located on the parasite and on macrophage surface play some role in the process of recognition of T. cruzi, (b) different macrophage carbohydrate-containing receptors are involved in the recognition of epimastigotes and trypomastigotes forms of T. cruzi, (c) N-acetylneuraminic acid residues located on the surface of trypomastigotes or macrophages impede the interaction of the parasite with these host cells, and suggest that (d) sugar binding proteins located on the macrophage surface participate in the recognition of beta-D-galactose and N-acetyl-D-galactosamine residues located on the surface of trypomastigotes and exposed after blockage or splitting off of N acetylneuraminic acid residues. Some lectins which bind to macrophages and block the ingestion of parasites did not interfere with their adhesion. PMID- 3085367 TI - [Comparative oncology of tumors of the digestive tract]. PMID- 3085368 TI - [Diseases of marmosets in colonies]. PMID- 3085369 TI - [The keeping and breeding of monkeys in the nurseries and reserves of the Institute of Experimental Pathology and Therapy of the Academy of Medical Sciences of the USSR]. PMID- 3085371 TI - [Modelling bacterial infections in monkeys]. PMID- 3085370 TI - [Genotoxic and pathogenic effects of aflatoxin B1 in experiments on monkeys]. PMID- 3085372 TI - [Management of a colony of marmosets]. PMID- 3085373 TI - [The use of monkeys to study problems concerning viral hepatitis]. PMID- 3085374 TI - [Modelling Acholeplasma infections in the monkey]. PMID- 3085375 TI - [Structuro-functional features of the central nervous system of the primate and the use of monkeys in studying mechanisms of behavior regulation]. PMID- 3085376 TI - [Laboratory diagnosis of anorectal gonorrhea]. PMID- 3085377 TI - Indoxylsulfate in milk. AB - Indoxylsulfate in 27 individual milk samples ranged from 25.4 to 111 micrograms/l (average 52.3 micrograms/l); pooled milk samples from 12 farms contained 81.1 micrograms/l (46.4-146 micrograms/l); the variation in indoxylsulfate concentration of dried skimmed milk over a period of one year amounted to 23%. This variability is likely attributable to regional and seasonal, and hence to feeding effects. The indoxylsulfate content of milk seems also to be dependent upon the degree of fermentation during processing of milk; yoghurt contained very low amounts of this component (6.4 micrograms/kg). On the other hand, heat treatment of the milk (HTST, UHT, sterilization) apparently does not affect its indoxylsulfate content. Indoxylsulfate concentrations in milk correlated positively with blood-serum indoxylsulfate content (r = 0.752, n = 20) and with the urea content of milk (r = 0.61, n = 12 pooled milks). Further research is suggested on the use of indoxylsulfate determinations as an aid to determine sweet whey added to dried skimmed milk, also as an analytical tool to differentiate bovine and sheep milks. PMID- 3085378 TI - Organochlorine pesticides and polychlorinated biphenyls in herring from the southern Baltic, 1983. AB - Hexachlorobenzene (HCB), alpha-, beta-, gamma- and delta-benzenehexachloride (BHC, HCH), p,p'-DDE, o,p'-DDD, o,p'-DDT, p,p'-DDD and p,p'-DDT (sigma DDT) and polychlorinated biphenyls (PCB) levels have been determined in muscle tissue of 187 herring (Clupea harengus) netted during 1983 in a different regions in the southern part of the Baltic Sea. The mean levels found for herring muscle tissue related to wet weight (microgram/kg) were: 14 HCB, 18 alpha-BHC, 23 beta-BHC, 14 gamma-BHC, delta-BHC remained undetected, 56 sigma BHC, 115 p,p'-DDE, o,p'-DDD and o,p'-DDT remained undetected, 84 p,p'-DDD, 51 p,p'-DDT, 250 sigma DDT and 530 PCB. The levels of organochlorine pesticides determined in wet muscles or extractable lipids of herring are nearly 2-3 times as high as those noted in fish sampled in the same area in two years before, whilst for PCBs the wet weight levels were comparable, and when based on a lipid weight are somewhat higher. The results are compared with levels found in herring collected in different regions of the Baltic Sea during 1965-1983, and reported previously by other authors. PMID- 3085379 TI - Organochlorine pesticides and polychlorinated biphenyls in cod from the southern Baltic, 1983. AB - Hexachlorobenzene (HCB), alpha-, beta-, gamma- and delta-benzenehexachloride (BHC; HCH), p,p'-DDE, o,p'-DDD, o,p'-DDT, p,p'-DDD and p,p'-DDT (sigma DDT) and polychlorinated biphenyls (PCB) levels have been determined in muscle tissue of 207 cod (Gadus morhua) netted during 1983 in different regions in the southern part of the Baltic Sea. The mean levels found for cod muscle tissue (microgram/kg) related to wet weight were: 0.65 HCB, 1.2 alpha-BHC, 9.0 beta-BHC, 2.8 gamma-BHC, delta-BHC remained undetected, 13 sigma BHC, 4.4 p,p'-DDE, o,p' DDD and o,p'-DDT remained undetected, 4.0 p,p'-DDD, 1.8 p,p'-DDT, 10 sigma DDT and 55 PCBs. The results are compared with levels found in cod caught in different regions of the Baltic Sea during 1967-1983, and reported previously by other authors. PMID- 3085380 TI - [Fabry disease, a disease with rheumatic aspects: radiology of soft tissue and bone changes in the hand]. AB - Fabry's disease is a hereditary lipid storage disease with deposition of ceramides in nearly all tissues. The lipid deposition in the skin and the synovial compartments causes an enlargement of the skin, the joint capsules and the tendon sheaths, which are recognizable by low KV radiography. The bones of the hand mainly show multiple enthesopathic ossifications of a peculiar kind at the insertions of fibrous structures and few intra- and extraarticular erosions. The clinical picture often simulates an inflammatory rheumatic disease. PMID- 3085381 TI - [Bacteriophages and bacteriocins of the genus Listeria]. AB - Since the discovery of the first Listeria bacteriophage by Schultz in 1945, more than 219 phages were isolated for L. monocytogenes, L. invanovii, L. innocua, L. seeligeri and L. welshimeri. To date, no phage for L. murrayi and L. grayi is described in the literature. Unless two phages found by Jasinska in a water sample, all the other phages, when the origin is mentioned, were isolated from lysogenic strains, with or without induction. Electron microscopic examination of 55 Listeria phages revealed that two L. innocua phages belonged to the Myoviridae family (tail with contractile sheath) whereas the 53 other phages of L. monocytogenes, L. ivanovii and L. innocua belonged to the Siphoviridae family (tail without contractile sheath). According to the length of the tail, phages of this second group were divided into three species (species 2685, 2671 and 2389). DNA/DNA hybridizations, performed with the method of Southern, after digestion of the DNAs with Eco RI, pointed out three genomic groups: one corresponded to a single phage of Myoviridae and the two others included phages of the Siphoviridae species 2671 and 2685, thus demonstrating a good correlation between ultrastructure and DNA relatedness. Serology of Listeria phages remained unclear. Host range studies showed that these phages are genus specific and allowed to type 34% to 80% Listeria strains. Phage typing of Listeria strains isolated during listeriosis epidemics and cross infections in nursery proved to be useful in order to elucidate epidemiology of this disease. Listeria phages were used to detect Listeria strains in various samples by phage fluorescent antiphage staining system and phage titer increase test. Some phages seem to induce prophylaxis against listeriosis when tested in animal listeric pneumonia and conjunctivitis models. The possible role of phages in the virulence of L. monocytogenes needs further investigations. Bacteriocins of Listeria, called monocins, were first described by Sword and Pickett in 1961. Monocins isolated by Hamon and Peron were resistant to trypsin, inactivated at 50 degrees C and at pH 4,5 and sedimented at low speed, suggesting that these bacteriocins might be in fact defective phages. This was confirmed by Bradley and Dewar by electron microscopic study. Host range of monocins included Listeria, Staphylococcus and Bacillus. PMID- 3085382 TI - [Experiences in the preparation of the secretory IgA and secretory component from human colostrum]. AB - With the isolation of secretory IgA and secretory component from human colostrum following the route communicated by Kobayashi some differences revealed with respect to the preparative results. Mainly problems arising from lactoferrin and IgM encouraged us to offer some varied laboratory instructions. PMID- 3085383 TI - Muscle fibre types and enzyme activities in healthy foals and foals affected by muscular dystrophy. PMID- 3085384 TI - Oestradiol-17 beta stimulates the release of luteinizing hormone and follicle stimulating hormone from bovine anterior pituitary cell cultures. PMID- 3085385 TI - Rectovaginal constriction in Jersey cattle. II. Light microscopic studies of tissues and in vitro cells. PMID- 3085386 TI - Rectovaginal constriction in Jersey cattle. III. Hydroxyproline levels in tissues. PMID- 3085388 TI - Dissimilar ruminal epithelial response to short-term and continuous intraruminal infusion of sodium n-butyrate. PMID- 3085389 TI - Determination of milk urea by flow injection analysis. PMID- 3085387 TI - Cells of sow mammary secretions. I. Morphology and differential counts during lactation. PMID- 3085390 TI - [Modified operative technic for perfusion of the isolated chicken liver]. PMID- 3085391 TI - Conformation of interstitial collagen of bovine rumen and skin. PMID- 3085392 TI - [Effect of biogenic amines (histamine and 5-hydroxytryptamine) on the motility and the muscles of the digestive tract of iguana (Liolaemus gravenhorsti, Reptila Squamata-Iguanidae)]. PMID- 3085393 TI - Postnatal changes of the ultrastructure in dog parathyroid cells. PMID- 3085394 TI - The urinary excretion of orotic acid and urea in dairy cows in early lactation. PMID- 3085395 TI - On the effect of xylazine on forestomach motility in sheep. PMID- 3085396 TI - [Tumors in zoo, ornamental and wild birds. A 25-year review (1960-1984)]. PMID- 3085397 TI - [Pathomorphology of so-called juvenile renal disease in the dog]. PMID- 3085398 TI - Solid carcinoma of the glandula superficialis palpebrae tertiae in a horse. PMID- 3085399 TI - Kinetic disposition and biodistribution of amoxycillin in Bubalus bubalis. PMID- 3085400 TI - [Comparative study of the cardiovascular and respiratory effects of fentanyl and pentazocine in combination with flunitrazepam, in the induction of neuroleptanalgesia in dogs]. PMID- 3085402 TI - [The number of mitosis chromosomes in the rainbow trout in relation to age]. PMID- 3085401 TI - [Alkaline phosphatase activity in blood serum and synovia of healthy and infected joints and non-infected joint inflammations in cattle]. PMID- 3085403 TI - [Salmonellae in milk and milk products]. PMID- 3085404 TI - [Cellular ultrastructure of the meningococcus when incubated in a continuous culture of human FL-line amnion]. AB - Some details of the ultrastructure of several meningococcal strains having had contacts with cells in continuous human amnion cell culture FL for 6 hours to 2 days have been defined with greater precision by means of electron microscopy. The study has shown that the contact of meningococci with the tissue culture is accompanied by the appearance of meningococcal forms with the defective cell wall, similar to L-forms: spheroplast, protoplast, gigantic cells and microcells, as well as budding variants. The meningococcal variants with the defective cell wall, appearing in the cell culture, and the forms occurring (in different proportions) in "ripe" meningococcal populations developing in the culture media for a long time and isolated from a human body have been found to have no essential differences in their fine structure. These data indicate that any external influences (meningococci are highly sensitive to such influences) produce sufficiently rapid changes, similar to L-transformation, in the fine structure of these microorganisms. PMID- 3085405 TI - [Epidemiological significance of carriers of hyaluronidase-active meningococci]. AB - To find out the epidemiological role of the carriers of hyaluronidase-positive meningococcal strains, their spread in the foci of meningococcal infection, as well as outside these foci, was studied. For this purpose, altogether 5059 persons from 40 family foci of infection and 40 organized groups were examined. The number of carriers of hyaluronidase-active meningococci, detected among those of them who had contacts with sick persons, was 13 times greater than among the persons having no such contacts. In preschool institutions with unfavorable morbidity situation this number was 16 times greater than in those with favorable situation. In the family foci carriers of hyaluronidase-active meningococci constituted 80-88 %. The percentage of the carriers of hyaluronidase-active meningococci causing cases of the generalized form of meningococcal infection varied in different groups. According to the results obtained in this study, the threshold percentage of such carriers constituted 30 in preschool institutions, 36 in boarding schools and 50 in common school and in hostels for adults. PMID- 3085406 TI - [Effect of a corpuscular polyvalent Pseudomonas aeruginosa vaccine on the proliferation and differentiation of hematopoietic stem cells and erythropoiesis]. AB - P. aeruginosa corpuscular polyvalent vaccine stimulates hematopoiesis in sublethally stimulated mice. The stimulating effect is dose-dependent. The most effective method of immunization is the intravenous injection of the vaccine. The degree to which the stimulation of hematopoiesis is manifested varies in different strains of mice. The stimulation of hematopoiesis is not linked with an increase in the content of erythropoietin. P. aeruginosa polyvalent corpuscular vaccine and monovaccine, prepared from P. aeruginosa strain 1313 and incorporated into the polyvalent vaccine, protect lethally irradiated mice in the postradiation survival test. PMID- 3085407 TI - [Immunogenicity of a chemical typhus vaccine and of a corpuscular radioantigen obtained from Rickettsia prowazekii]. AB - The protective activity of chemical typhus vaccine and R. prowazekii corpuscular radioantigen (CRA) was studied. Guinea pigs were immunized with doses of 32 and 48 antigenic units. Antibody production was assayed in the complement fixation test. On days 7, 15, 21, 30 and 60 after immunization the animals were challenged with R. prowazekii introduced in an amount of 10(5) minimum embryonal infective doses (MEID). On day 30 some of the animals were challenged with 10(3) MEID of R. typhi. The results demonstrated that both preparations were highly immunogenic and capable of protecting most of the animals from 10(5) MEID of R. prowazekii. Immunity developed earlier after immunization with CRA. The guinea pigs immunized with CRA, purified in percoll density gradient, and challenged with 10(3) MEID of R. typhi on day 30 showed a high level of cross immunity. In all control animals high fever and periorchitis were observed. PMID- 3085408 TI - [Biochemical and immunochemical study of antigen preparations of Rickettsia prowazekii]. AB - The biochemical and immunochemical study of the qualitative composition of R. prowazekii antigenic preparations, isolated and purified by different methods, indicates that these preparations contain high-molecular polypeptide 3 (133600 D), morphologically linked with the cell membrane of R. prowazekii. The method of adsorption chromatography on calcium phosphate permits obtaining specific rickettsial antigens with a greater degree of purification from ballast admixtures than the methods of acid precipitation and gel filtration on Sephadex G-200. PMID- 3085409 TI - [Protective effect of a corpuscular polyvalent Pseudomonas aeruginosa vaccine in generalized chronic Pseudomonas aeruginosa infection in mice with cyclophosphamide-induced leukopenia]. AB - The prophylactic effect of immunization with P. aeruginosa polyvalent corpuscular vaccine has been shown on the model of P. aeruginosa generalized chronic infection in mice with leukopenia induced by the intraperitoneal injection of cyclophosphamids. This effect is manifested by the increased resistance of the animals to sublethal doses of P. aeruginosa strain, as well as by more intense general and specific immunological responses in the infected animals (the increase of specific antibody titers, the number of leukocytes in the blood serum and the phagocytic activity of the cells of peritoneal exudate). PMID- 3085410 TI - [Effect of a controlled abacterial environment on the Pseudomonas aeruginosa infection of suppurative wounds]. AB - The present work deals with the data on the isolation rate of P. aeruginosa from suppurative wounds of different origin during their treatment by the commonly used methods under dressings and by the open method under the conditions of controlled germ-free environment. The results of the immunotyping of P. aeruginosa strains isolated from patients treated by different methods are presented. The dynamics of changes in the isolation rate of P. aeruginosa at different periods of treatment, both by the open method and with the use of dressings, is shown. Among P. aeruginosa strains isolated from suppurative wounds, those belonging to immunotypes 6, 7 and 2, as well as nontyping strains, occurred most frequently. Treatment in the controlled germ-free environment permits the protection of the wound surface from hospital infection. During treatment with the use of dressings the cases of hospital infection were revealed (31.3%). Such infection occurred, as a rule, at a later period of treatment. PMID- 3085411 TI - [Electron microscopic study of the cytopathogenic action of meningococci in a continuous human amnion cell culture]. AB - The electron-microscopic study of the interaction of meningococci with continuous human amnion cell culture F1 has revealed that this process comprises 3 stages. The study has shown that, following the adhesion of meningococci to the surface of cells F1, these cells are invaded by individual coccal forms of meningococci. In response to infection vacuoles appear in the cytoplasm of the cells. Meningococci are either phagocytosed inside these vacuoles, or their release into the intercellular space and the death of the infected by meningococci are observed. When the cells are infected by cytopathogenic strains, the infectious process results in the appearance of degenerative changes in the cells. PMID- 3085412 TI - [Use of an experimental model of mixed chlamydial-gonococcal infection in ovo for evaluating the etiotropic action of chemopreparations]. AB - The detection of the differentiated chemotherapeutic activity of tetracyclin and penicillin has been used as an example for demonstrating the possibility of using the experimental in ovo model of mixed chlamydial and gonococcal infection for the detection and primary selection of effective etiotropic preparations, simultaneously affecting Chlamydia trachomatis and Neisseria gonorrhoeae. PMID- 3085413 TI - [Chemiluminescence of human neutrophils as affected by opportunistic microbes]. AB - Chemoluminescence of neutrophils obtained from 24 healthy donors in response to Staphylococcus aureus Cowan, Pseudomonas aeruginosa and Escherichia coli preopsonized with 5% fresh autologous serum or with pooled normal sera was studied. Chemoluminescent response to S. aureus was most pronounced in comparison with that to the other microbes. Neutrophils from most of the donors showed chemiluminescent response of medium intensity, their stimulation index (SI) being 10-12; neutrophils from some donors showed low response (their SI not exceeding 10), and some donors provided highly responsive neutrophils (their SI exceeding 20). Neutrophils from the latter group of donors retained their high SI over the longest period of time (60 minutes and more). Experiments made under the conditions of preopsonization with pooled normal sera indicated that differences in the response of neutrophils were linked with the individual features of these cells. Low response to P. aeruginosa and E. coli was, possibly, due to the antiphagocytic activity of these microorganisms. Differences in the response of neutrophils to antigens of opportunistic microbes, as well as in the dependence of this response from serum factors, may finally determine the result of the interaction between host defence factors and microorganisms at the infection atrium. PMID- 3085414 TI - [Various indices of immunity in patients with alcoholic delirium]. AB - Seventy-four patients with alcoholic delirium were studied for the parameters of the T- and B-system of immunity and natural resistance. The patients versus normal donors presented a statistically significant decrease in the number and proliferative activity of T-lymphocytes, an increase in IgA, as well as a reduction in levels of lysozyme, complement and bactericidal activity of the serum. The presence of immunological shifts after the completion of detoxifying therapy suggests that treatment should be continued even after the disappearance of psychic disturbances. PMID- 3085416 TI - [Bacterial septicemia: an unrecognized complication of hemochromatosis. Study of 3 cases and review of the literature]. PMID- 3085415 TI - [Sexual disorders among men with myotonic dystrophy]. AB - Sexual function was studied in 15 males with myotonic dystrophy. For this purpose a structural analysis was employed and blood levels of gonadotrophins and testosterone were radioimmunoassayed. Peculiar endocrine disorders were found to be largely responsible for disruption of the neurohumoral component of the copulative cycle. The results of the study may be useful for the treatment of sexual disturbances in myotonic dystrophy and for the differential diagnosis. PMID- 3085417 TI - Rapid regression of macroprolactinomas by the new dopamine partial agonist terguride. AB - Two patients with macroprolactinomas were treated with the partial dopamine agonist, terguride. The prolactin (Prl) levels were lowered very effectively and in both cases the clinical symptoms improved markedly during the first days of treatment. Computerized tomography (CT) and magnetic resonance imaging (MRI) follow-up studies showed distinct tumour shrinkages which were first documented by MRI within 2 weeks of treatment. Tumour residues were, however, still demonstrable by MRI after more than one year respectively 3 months of therapy. In principal, results from both imaging techniques were comparable with the exception of the one year follow-up study of patient 1. In CT no residual tumour mass was visible whereas MRI showed only little reduction when compared to the 30th week scan. Throughout the treatment terguride was well tolerated without any side effects up to a maximal daily dosage of 3 mg given orally. Presumably the partial agonistic features of terguride contributed to the good tolerance of the treatment as compared to that of full dopamine agonists like bromocriptine of lisuride. Thus, these preliminary results indicate that terguride may be a beneficial alternative in the treatment of prolactinomas and other hyperprolactinaemic states. PMID- 3085418 TI - Stimulation of parathyroid hormone secretion by EDTA infusion--a test for the differential diagnosis of hypercalcaemia. AB - A constant EDTA infusion of 24 mg/kg/h during 60-120 min was given to 26 patients with primary hyperparathyroidism (HPT), 8 patients with hypercalcaemia of other origin and 10 healthy control subjects. PTH and ionized calcium concentrations were measured at 5-10 min intervals. In all three groups the infusion caused a linear decrease in plasma ionized calcium. In both the HPT patients and the healthy subjects there was a prompt increase in the serum levels of parathyroid hormone (PTH) until a plateau was reached. The PTH response of the HPT patients appeared already within the hypercalcaemic range and the plateau value was attained at higher levels of PTH and ionized calcium than in the healthy subjects. The enhanced response distinguished half of the HPT patients with basal PTH values within the reference range from the healthy controls. The patients with nonhyperparathyroid hypercalcaemia displayed no increase in PTH values until the ionized calcium concentration was reduced far into or below the reference range. Thus the EDTA infusion permitted a complete differentiation between HPT and other causes of hypercalcaemia. In most cases an infusion over 30 min was sufficient for this purpose. PMID- 3085419 TI - Interindividual variation in the absorption of glibenclamide in man. AB - To investigate the interindividual variation in the absorption of sulphonylureas and its relation to unexpected hypoglycaemia during therapy with these drugs, serum concentration profile of glibenclamide, as well as plasma glucose and insulin response after an oral intake of glibenclamide were studied in 17 patients with non-insulin-dependent diabetes mellitus. In 12 patients glibenclamide was rapidly absorbed, reaching a peak concentration of 138.0 +/- 15.8 ng/ml (mean +/- SEM) at about 2 h. However, in 5 patients the absorption of glibenclamide was delayed and reached a serum peak of 134.1 +/- 29.5 ng/ml at later than 4 h. This delayed absorption was reproducible. There were no significant differences in age, duration of diabetes, per cent of ideal body weight, fasting plasma glucose or HbA1C between the rapid absorption group and the delayed group. However, autonomic nerve function, assessed by coefficient of variation of R-R intervals, was significantly impaired in the latter group in comparison with the former. Plasma glucose and insulin response to glibenclamide was also delayed in the delayed absorption group. PMID- 3085421 TI - Autoimmune mechanism of pure red cell aplasia: suppression of erythroid colony formation of bone marrow cells by autologous peripheral T cells in an infant. PMID- 3085420 TI - Lipids, apolipoproteins and steroids in serum and in fluid from stimulated and non-stimulated human ovarian follicles. AB - Steroid production depends on the cholesterol (CH) substrate supplied by circulating lipoproteins which are internalised in the cells by receptor-mediated mechanisms. Low density lipoproteins (LDL) stimulate progesterone production in vitro. However, studies on follicles indicate low levels of LDL in follicular fluid (FF1). In the present study FF1 was obtained by ultrasound-guided punctures just before ovulation from 17 women participating in an in vitro fertilization programme. Serum was obtained simultaneously. Follicular development was stimulated with hMG-HCG or clomiphene-hMG-hCG combinations. In another 8 women FF1 was collected in connection with surgery for sterilization. FF1 levels of CH, triglycerides (TG), phospholipids (PL), apolipoprotein A1 and B (apoA1; apoB), oestradiol and progesterone were assayed in both groups as were the corresponding serum levels in the stimulated patient group. The FF1 levels of apoA1, TG and PL were approximately half of the levels in HDL in normal serum in both groups. However, CH was slightly lower in the stimulated group. ApoB was not detectable in FF1. Oestradiol was similar in both groups while progesterone was much higher in the stimulated than in the non-stimulated cycles. FF1 levels of apoA1 correlated positively to CH and PL in both groups and to progesterone in the stimulated follicles, while the correlation was negative in the other group. The absence of apoB and the levels of CH, TG, PL and apoA11 indicate that high density lipoprotein (HDL), but not LDL is present in FF1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085422 TI - Identification of abnormal hemoglobin (J Lome): beta 59 (E3) lysine----asparagine in a Japanese. PMID- 3085423 TI - Platelet and leukocyte lipoxygenase products in a patient with chronic granulocytic leukemia undergoing syngeneic bone marrow transplantation. PMID- 3085424 TI - Hazardous mobility in the elderly. PMID- 3085425 TI - Family support--the challenge in personal care homes. PMID- 3085426 TI - Wandering in the elderly. PMID- 3085427 TI - Relocation of the elderly. PMID- 3085428 TI - Premedication with oral and rectal diazepam. AB - It has been postulated that esophageal retention of diazepam tablets is a problem of clinical significance, and that rectal administration is an advantageous alternative. To test this hypothesis, 100 patients were randomly allocated to premedication with either 15 mg diazepam orally or 10 mg diazepam as a rectal solution. A double dummy technique was used. A sedative effect was seen in 23 (50%) of the patients premedicated by mouth (O-group), but only in eight (20%) of those premedicated rectally (R-group) (P less than 0.05). Four patients (9%) in the O-group and seven (18%) in the R-group were unacceptably anxious before induction (n.s.). The plasma concentrations in the tablet group were nearly twice the concentrations found in the rectal-solution group, but no correlation between premedication effect and plasma concentration was found. Timing of premedication was very inaccurate, and this favored oral administration because of a more prolonged effect. No evidence of persistent esophageal retention was found. PMID- 3085429 TI - Correlation of gas exchange impairment to development of atelectasis during anaesthesia and muscle paralysis. AB - Pulmonary gas exchange and the development of atelectasis were studied in eight essentially lung-healthy patients, awake and during halothane anaesthesia with mechanical ventilation. Gas exchange was evaluated by a multiple inert-gas elimination technique and conventional blood-gas analysis, and atelectasis was studied by computerized tomography (CT). Ventilation and lung perfusion were well matched in the majority of the patients when awake. In two patients there was low perfusion of poorly ventilated regions (low VA/Q). One patient had a shunt corresponding to 4% of cardiac output. None of the patients showed signs of atelectasis on the CT scans. After 15 min of anaesthesia, shunt had appeared in all patients, ranging from 1% in two patients (unchanged from the awake state) to 17%. The major VA/Q mode was widened and ventilation of poorly perfused regions (high VA/Q) was noted in seven patients. Densities in dependent lung regions (interpreted as atelectasis) were seen on the CT scans in six patients. The extent of atelectasis was significantly correlated both to the magnitude of shunt (r = 0.93, P less than 0.01) and to the impairment of arterial oxygenation (r = 0.99, P less than 0.001). The findings indicate that atelectasis in dependent lung regions during halothane anaesthesia creates shunting of blood flow and that atelectasis is the major or sole cause of impaired gas exchange in the lung healthy, anaesthetized subject. PMID- 3085430 TI - Ventilatory CO2-response after alfentanil and sedative premedication (etomidate, diazepam and droperidol). A comparative study with human volunteers. AB - The ventilatory response to CO2 after intravenous bolus injection of alfentanil 15 micrograms/kg was studied in a group of 10 healthy volunteers of both sexes, aged 19 to 30 years. Following randomized intravenous premedication with either placebo, diazepam 5 mg, droperidol 5 mg or etomidate 10 mg, a total of four test series were performed with each individual in two-weekly intervals, in order to assess the additive effect of central depressants on opiate-induced respiratory depression. CO2-response curves were obtained during six-minute rebreathing periods up to 60 minutes after alfentanil. Slope as well as position of the curves were compared with pre-drug control values. In contrast to previous work with fentanyl 4 micrograms/kg, CO2-response curves after alfentanil 15 micrograms/kg were usually displaced to the right without concomitant decreases in slope. Ventilation almost completely returned to control levels after one hour. Due to strong inter- and intraindividual variations, no clearly significant differences could be observed between the premedication groups. Alfentanil plasma concentrations, determined by radioimmunoassay at 1, 3, 6, 10, 20, 30, 45, 60, 75 and 120 minutes after injection, showed only a poor correlation to the changes of the CO2-response curves. PMID- 3085431 TI - Coronary vasospasm after myocardial revascularisation. Treatment by verapamil. AB - Coronary vasospasm occurring after myocardial revascularisation must be quickly and efficiently treated to avoid the haemodynamic complications that it may cause. Treatment by nitroglycerin intravenously (i.v.) is not always efficient and an alternate possibility of treatment is essential. During the period from March 1982 to August 1983, we observed in our institution three patients with coronary vasospasms occurring after myocardial revascularisation which did not respond to nitroglycerin i.v. and were successfully treated by verapamil. Recurrence of vasospasm was prevented in those cases by verapamil perfused i.v. (dosage: 0.37 to 0.75 microgram/kg/min). The clinical evolution of these 3 cases are described here. Dosages of verapamil used to treat and to prevent the incident are discussed. The limitations of this therapy are briefly reviewed. PMID- 3085432 TI - Intraosseous pressures of oxygen and carbon dioxide in coxarthrosis. AB - We have investigated the intraosseous partial pressures in 15 patients suffering from primary arthrosis of the hip. The measurements were performed by a mass spectrometer via a specially designed inlet system. The average pO2 and pCO2 values in the femoral head were 8.2 and 6.8 kPa (62 and 52 mmHg), respectively, and in the greater trochanter 6.6 and 5.1 kPa (51 and 39 mmHg). The average intraosseous pressures in the femoral head and greater trochanter were 5.5 and 3.0 kPa (42 and 23 mmHg). The differences between the intraosseous pressures, pO2 and pCO2 in the greater trochanter and the femoral head were all significant. PMID- 3085433 TI - Hemodynamics and metabolism in arthrosis. Studies in the rabbit knee. AB - Arthrosis was induced in the rabbit knee, making it unstable by ligament resection. Acidity and hypercapnia were found in the synovial fluid of the arthrotic knees, whereas oxygen partial pressure was normal. In arthrotic subchondral bone the intraosseous pressure and oxygen partial pressure were increased; intraosseous phlebography showed venous congestion. Histologic specimens showed increased subchondral bone formation, loss of cartilage and total depletion of glycosaminoglycans. The synovial membrane was hyperplastic and fibrosis was found in the underlying tissue. We suggest that changes in environmental haemodynamics and metabolism, although secondary in nature, may play an important role in the arthrotic process. PMID- 3085434 TI - An improved algorithm and a computer program for the analysis of capillary gas exchange. AB - In most models of capillary gas exchange, the binding curves for O2 and CO2 are represented by simple analytical expressions, and the interactions among the haemoglobin ligands are either neglected or are assigned fixed values independent of PO2, PCO2, pH and red cell DPG. We here present algorithms and a computer program in which the binding curves are described in a near-rigorous manner. This enables solution of a set of typical equations for a unit of blood which undergoes gaseous and proton exchange. We have applied the algorithms to the problem of calculating pulmonary blood flow from the gaseous exchange in the lung by the single-breath method of Kim et al. (1966), where the CO2 binding curves of arterial and mixed venous blood are approximated by straight lines. The application of the algorithms shows that this approximation introduces significant errors in the calculated pulmonary blood flow. PMID- 3085435 TI - Failure of GABAergic inhibition: a key to local and global seizures. AB - Current working models of nervous system function based on many experimental observations are presented, often supported by extensive immunocytochemical findings, and partly by extrapolation of such findings into reasonable potentialities. Particular emphasis is placed on consideration of the roles of inhibitory GABAergic neurons in normal and abnormal information processing in the CNS. PMID- 3085436 TI - Contemporary methods in neurocytology and their application to the study of epilepsy. AB - The contemporary neuroanatomist has a number of available methods to analyze epileptic brain tissue. Many studies have utilized Nissl- and Golgi-stained preparations to determine that gliosis and neuronal loss occur at epileptic foci as well as a decrease in the dendritic spine density. These structural changes did not reveal any specific basic mechanism that may cause epileptic activity. In contrast, the relatively newer techniques in neurocytology provide functional data that relate to the physiology and chemistry of the brain tissue. The use of immunocytochemical, histochemical, and receptor ligand-binding autoradiographic methods have aided in the understanding of cellular neurochemistry in both normal and epileptic tissue. In addition, the use of intracellular horseradish peroxidase and recording and quantitative morphological methods at both light- and electron-microscopic levels has helped gain insights into the functional state of synapses and neurons. Together, these methods have been utilized to help unravel the mystery of epilepsy. Our laboratory has utilized immunocytochemical and quantitative light- and electron-microscopic methods to analyze four models of epilepsy; two resemble posttraumatic focal epilepsy, and the other two are genetic models of epilepsy. Our data indicate that a preferential loss of cortical GABAergic, inhibitory terminals occurs at posttraumatic epileptic foci. In contrast, the genetic models of epilepsy did not display a loss of GABAergic terminals. Instead, specific brain regions of epileptic animals had an increased number of GABAergic neurons and terminals. These data indicate that two different neuronal circuits may provide the anatomical substrate for epileptic activity: loss of inhibition and disinhibition. PMID- 3085438 TI - Regional cerebral blood flow and metabolic rates in human focal epilepsy and status epilepticus. AB - Positron emission tomography with the oxygen-15 steady state or bolus inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen extraction ratio (OER) and oxygen consumption (CMRO2) in 25 patients with partial complex seizures during the interictal state and in 5 patients during status epilepticus. Glucose utilization (CMRglu) was also studied in one case of status epilepticus with the 18F-fluorodeoxyglucose technique (18FDG). Interictal scans showed zone(s) of hypoperfusion and hypometabolism without significant variation of the OER in approximately 80% of patients. In 62%, there was a strong correlation between the overall EEG localization and the area(s) of hypoperfusion and hypometabolism. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the electroencephalograph (EEG) abnormalities. Comparison of the different values of CBF, CMRO2, and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease of OER; the latter was always the most prominent in the region of the epilepticus focus determined by serial EEG recordings. These results showed that the supply of oxygen by blood flow is large enough to meet metabolic demand. When comparing these values with CMRglu, it appeared that the relative changes in CMRglu and CBF were very similar, indicating that the increase in blood flow correlated with the enhancement in glucose utilization. The observed imbalance between blood flow, glucose utilization, and oxygen consumption could suggest that an impairment of oxygen utilization by the mitochondria could occur in the epileptic focus during prolonged status epilepticus. PMID- 3085437 TI - Epilepsy and the blood-brain barrier. AB - A concern for the possible role of the blood-brain barrier (BBB) in the epilepsies was based on ultrastructural studies that demonstrated increased micropinocytosis in cerebral capillaries during seizures. Continued interest in the structure of the BBB has led to the demonstration that, in human psychomotor epilepsy, there is a thickening of the capillary basement membrane. These studies also suggest that an increase in capillary mitochondria and interendothelial tight junctions may characterize seizure-traumatized brain regions. These studies forecast an increased interest and understanding of the ultrastructural events associated with capillaries in seizure states. Additional focus on the BBB comes from the clinical use of anticonvulsant drug levels in the control and treatment of seizures. Debate as to whether free drug levels are appropriate continues. The brain capillary is the interface between blood-borne drug and the target site, and thus an increased understanding of the events associated with brain-plasma exchange has been sought. The concept that only that fraction of drug that is freely dialyzable is available for equilibration across the BBB is not supported by recent studies, which demonstrate that protein-bound ligands are able to dissociate and gain access to the brain in the course of a single capillary transit. It has been established that albumin-bound fatty acids, steroids, and anticonvulsant drugs more readily distribute into tissues than previously believed. Thus, traditional free drug hypotheses need to be expanded to account for the fact that dissociation constants measured in vitro are not the same as those measured in vivo. The BBB also regulates nutrient availability to the brain, and under normal conditions excess substrate is made available to the brain for metabolism. Indirect evidence is available to suggest that during seizures, BBB transport may indeed be the rate-limiting step. Specifically, glucose availability to the seizing brain may be restricted to such a degree that brain glucose utilization rates are no longer independent of plasma glucose levels. If it can be proven that BBB transport is the rate-limiting step during seizures, then it would be possible to augment brain glucose utilization rates by increasing plasma glucose levels. In addition, a depression of brain glucose utilization could be achieved by inducing hypoglycemia. It is not fully understood whether BBB rate limitation would persist postically, nor is it known whether BBB alterations may be global or restricted to the seizure focus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3085439 TI - Neuronal firing patterns from epileptogenic foci of monkey and human. AB - The chronic, recurrent seizures induced in the monkey by cortical scarring occur spontaneously for years and share much of the phenomenology of spontaneous seizures of focal cortical onset in the human. Chronic extracellular recording in the focus of the chronic epileptic monkey reveals: A spectrum of abnormalities of unit firing ranging from grossly abnormal firing patterns to normal activity. Group I (highly epileptic) neurons fire exclusively in bursts, which are invariant during different behavioral states and during operant conditioning. Although firing within the bursts is not easily modified, the interburst interval can be modified indicating that these apparently denervated cells still have some synaptic input. All group I cells are pyramidal neurons. Group II (weakly epileptic) neurons exhibit variable burst firing, which may be intermixed with normal unit firing. The firing patterns of these cells can be modified by synaptic inputs. During operant conditioning, burst firing can decrease; during drowsiness or when inattentive, burst firing can approach that characteristic of group I cells. There is a direct relationship between the number of group I epileptic (pacemaker) neurons in the focus and the epileptogenicity of that focus as measured by frequency of spontaneous seizures in that monkey. The distribution of neurons encountered in the focus varies. On average, approximately 10% are group I (pacemaker) neurons; group II constitute 40%; and 50% of cells encountered exhibit normal firing patterns. In addition to firing in unstructured bursts, an unusual burst structure termed the long-first-interval (LFI) burst has been described that appears to be unique to the chronic focus. It is so named because the first interspike interval is longer than the remaining interspike intervals in the burst. The long first interval is extraordinarily invariant. There is little relationship between unit firing in bursts and the interictal EEG. During early parts of a spontaneous seizure, the two events become time locked. During seizures, unit firing is synchronous with surrounding neurons and the spike portion of the EEG (as in penicillin foci). Firing of group I neurons does not change significantly preceding a spontaneous seizure. Thus, group I neurons appear to act as pacemakers to the focus and group II cells provide the critical mass that, when synchronized to the burst firing of the pacemakers, is capable of initiating the ictal event. PMID- 3085440 TI - [The effects of sodium valproate on neuron discharges in the superior colliculus of the cat]. PMID- 3085441 TI - [An aspect of cell level changes in the sugar-induced cataractous lens]. PMID- 3085442 TI - [The role of aldose reductase in diabetic corneal epitheliopathy. Second report: The corneal epithelium of galactosemic rats]. PMID- 3085443 TI - Three-dimensional CT reformation in children. AB - Three-dimensional computed tomographic (CT) reformation has proven useful in the evaluation of congenital malformations of the brain as well as in the surgical approach and postoperative assessment of craniofacial anomalies in children. This technique was performed on 41 patients, of whom eight are presented. The congenital anomalies of semilobar holoprosencephaly and colpocephaly are described. Six representative cases of craniofacial anomalies with pre- and postoperative examinations include Crouzon syndrome, orbital fibrous dysplasia, frontonasal encephalocele, cranial involvement from neurofibromatosis, Treacher Collins syndrome, and a Tessier III facial cleft. Addition of the dimension of depth provides a view heretofore not obtainable by standard imaging techniques and allows more accurate diagnosis as well as a more specific approach to surgical planning and follow-up. PMID- 3085444 TI - Experimental Staphylococcus aureus brain abscess. AB - The virulent organism Staphylococcus aureus produced brain abscesses that were quantitatively and qualitatively different from those caused by less virulent organisms. S. aureus abscesses created larger lesions, as earlier ependymitis, delayed progress toward healing, and caused areas of inflammatory escape outside the collagen capsule. Imaging tests revealed similar findings: the abscesses were larger, had more extensive central necrosis, and showed earlier evidence of ependymitis. This virulent organism also demonstrated that white matter is more susceptible than overlying gray matter to destruction by infection. The pattern of spread and other histologic findings suggest that collagen capsule formation has less of an infection "containment" function than was previously thought. PMID- 3085445 TI - Optimal visualization of the cerebrospinal fluid on MRI. PMID- 3085446 TI - Acute subdural hematomas: atypical CT findings. AB - Seventy-one patients with acute subdural hematomas were examined by CT within 72 hr of a documented head injury. Lesions often did not have the classical appearance of a homogeneous, high-density extracerebral collection of blood in a crescentic configuration. Specifically, 28 patients (39%) had mixed-density subdural hematomas (MDSDH) with various degrees of low-density blood within the subdural space. In 10 of these 28 patients, the hematoma had a relatively localized mass effect with a convex inner margin, occasionally mimicking the appearance of an epidural hematoma. The MDSDH group differed from the typical homogeneous high-density subdural hematomas in that they were larger (average maximal thickness was 18.1 mm versus 8.0 mm), had more midline shift, and had a higher mortality rate (50% versus 26%). Four patients with MDSDH demonstrated an unusual pattern of ventricular compression with trapping of cerebrospinal fluid in the body of the ipsilateral ventricle and compression of the body of the contralateral ventricle. This pattern has to our knowledge not been previously described. Possible causes of the low-density regions within the hematomas include unclotted blood in an early stage of hematoma development, serum extruded during the early phase of clot retraction, or cerebrospinal fluid within the subdural space due to an arachnoid tear. PMID- 3085447 TI - Flow analysis with digital subtraction angiography: 1. Description of a simplified flow model. AB - An inexpensive, simplified flow model for use with digital subtraction angiographic (DSA) equipment is described. System tests show that the model gives reproducible data with a standard deviation of +/- 2.6%. Flow analysis also reveals an appropriate response to flow rates of 20-240 ml per min. The flow model can be used to investigate many of the variables and sources of error in DSA flow measurements. PMID- 3085448 TI - Flow analysis with digital subtraction angiography: 2. Acquisition and accuracy of transit-flow measurements. AB - A steady-state flow model was used to optimize methods of data analysis, to investigate variables that affect the time-density curves, and to determine the accuracy of transit-flow measurements with digital subtraction angiography. The most accurate data were obtained by using a small region of interest placed within the vessel, averaged data acquisition, and a gamma-variate fit applied to the time-density curve. The integrated area of the curve depended on the flow, vessel size, amount of iodine injected, framing rate, and the kVp. The integrated area was not affected by the mAs; the matrix size; or the volume, concentration, or rate of injection of the contrast material. Subject density, image intensifier mode, and field size did not affect the curves except for their contribution to scatter and beam hardening. There was good correlation between digital subtraction angiographic transit-flow measurements and known flow values. PMID- 3085449 TI - Periventricular leukomalacia in combination with intraventricular hemorrhage: sonographic features and sequelae. AB - Periventricular leukomalacia (PVL) is well recognized as a relatively uncommon yet particularly serious complication of prematurity. Although the sonographic features of PVL have been described, its association with intraventricular hemorrhage (IVH) has not been emphasized. Reviewing 26 consecutive cases of PVL in neonates of 34 weeks or less gestational age, significant associated hemorrhage was found in six (23%). Small quantities of blood were also noted in most of the other 20 infants. Of the six infants with both significant IVH and PVL, five required ventricular shunt and all had particularly poor clinical outcomes. In the neonates who required surgical intervention, rapid ventricular enlargement was accompanied by extensive periventricular cyst formation. Eventually, the septations within the cysts and frequently even the ependyma of superior/posterior lateral ventricles degenerated. Cysts merged imperceptibly with the ventricles giving an appearance that mimicked severe hydrocephalus. This was termed "pseudoventricle formation," as the large intracerebral cerebrospinal fluid spaces are primarily porencephaly and not enlarged ventricles. Response to shunting was minimal by sonography in all five cases and multiple shunt revisions were required in four. Clinical follow-up in children with significant IVH in combination with PVL has shown severe mental retardation and tetraplegia in all cases. PMID- 3085450 TI - Concurrent hydromyelia and diastematomyelia. AB - Hydromyelia was discovered in six of 13 patients with diastematomyelia. In one patient, hydromyelia affected only the segments of spinal cord above the diastematomyelia. In five patients, hydromyelia extended downward from the single cord into one or both hemicords. Because hydromyelia and diastematomyelia occur simultaneously, because they may produce very similar clinical changes, and because simultaneous or sequential surgical correction of both conditions may be necessary to achieve the best clinical result, the possibility of hydromyelia should be evaluated specifically in each patient demonstrated to have diastematomyelia. PMID- 3085451 TI - Diagnosis and evaluation of spondylolisthesis and/or spondylolysis on axial CT. AB - A critical review was made of the CT findings in 300 patients who underwent axial CT of the lumbar spine in which spondylolysis and/or spondylolisthesis had been diagnosed. Findings indicate that axial CT is superior to conventional radiographs in several areas: (1) for consistent and accurate demonstration of spondylolysis, (2) for disclosing the various changes in the apophyseal joints associated with degenerative and reverse spondylolisthesis, and (3) for uncovering minimal degrees of spondylolisthesis by the presence of a pseudobulging disk in many cases with equivocal or negative radiographs. Axial CT is a highly accurate method for diagnosing and evaluating spondylolysis and all types of spondylolisthesis. PMID- 3085452 TI - Intradural herniated cervical disk: a case report and review of the literature. PMID- 3085453 TI - Intradural lumbar disk herniation. PMID- 3085454 TI - Myelography with metrizamide: effect of contrast removal on side effects. AB - Moderately severe side effects, such as prolonged headache, nausea, vomiting, or psychoneurologic symptoms, were noted in 27 (32%) of 84 patients in whom the contrast medium was not removed. Conversely, among 73 patients from whom 20-25 ml of cerebrospinal fluid with the contrast medium was removed, only 10 (14%) experienced adverse effects, a statistically significant reduction. Although new contrast agents, such as iohexol and iopamidol, are reportedly less toxic than metrizamide, the contrast-removal technique described here may be indicated when large amounts of any contrast medium are used. PMID- 3085455 TI - Use of sitting position to relieve myelographic obstruction. PMID- 3085456 TI - Acute sinusitis mimicking antrochoanal polyp. AB - Three cases of antral sinusitis that presented in an unusual fashion are reported. In each case, the inflamed, swollen sinus mucosa became redundant and prolapsed into the nasal cavity through a widened sinus ostium, mimicking the findings of an antrochoanal polyp. The cases represent the first report in the radiographic literature of this unusual manifestation of maxillary sinusitis. PMID- 3085457 TI - Modified scalp vein needle for arterial puncture in infants. PMID- 3085458 TI - Acoustic neuromas in children. AB - Although unilateral acoustic neuromas in children are rare, they do occur. There is no gender predilection and the clinical symptoms and signs are similar to those seen in adults. They tend to occur in the absence of neurofibromatosis and are usually benign. Our patient is the youngest yet reported with documented unilateral acoustic neuroma; moreover; she is the first child in whom this tumor has been proven to be malignant both by histopathology and subsequent clinical behavior. PMID- 3085459 TI - Fatal brain edema after contrast-agent overdose. PMID- 3085460 TI - Delayed spinal subarachnoid hematoma: a rare complication of C1-C2 cervical myelography. PMID- 3085461 TI - CT scan in progressive supranuclear palsy. PMID- 3085462 TI - Selective enhanced CT. PMID- 3085463 TI - Dose-related effects of intracoronary nitroglycerin on coronary hyperemia in patients with coronary artery disease. AB - Although intracoronary nitroglycerin (NTG) is frequently required during percutaneous transluminal coronary angioplasty or thrombolysis, the dose-related hemodynamic effects and the extent to which intracoronary NTG--induced coronary hyperemia is limited in patients with coronary artery disease have not been defined. Therefore, we studied 19 patients with coronary artery disease (nine with no or minimal luminal narrowing of the left anterior descending coronary artery [group 1] and 10 with significant left anterior descending coronary stenosis [group 2]; mean arterial pressure and thermodilution coronary sinus and great cardiac vein blood flow were measured during bolus administrations of 50, 200, and 300 micrograms of intracoronary NTG. During the NTG-induced hyperemia, mean arterial pressure decreased 0%, 4% (both p = NS), and 6% (p less than 0.05) after 50, 200, and 300 micrograms doses, respectively. heart rate did not change. Global coronary hyperemia was greatest for 200 micrograms with coronary blood flow increasing (74 +/- 32% in group 1 and 53 +/- 25% for group 2) but was significantly different from 50 micrograms only in group 2 patients. Moreover, the regional coronary blood flow responses were attenuated in group 2 compared to group 1 for 50 micrograms, 18 +/- 13% vs 38 +/- 18%, and for 200 micrograms, 35 +/- 15% vs 72 +/- 34% (both p less than 0.05), with the reduction of regional coronary resistance in group 2 attenuated for all three doses of intracoronary NTG. The 300 micrograms dose did not provide further augmentation of either global or regional coronary blood flow or greater reduction in coronary resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085465 TI - Computerized detection of the lactate threshold in coronary artery disease. AB - A computer program for identifying oxygen consumption at the lactate threshold was evaluated by expired gas analysis during treadmill exercise testing in 15 patients with prior myocardial infarction. There was a strong correlation (r = 0.85, p less than 0.001) between computer-identified oxygen consumption (14.1 +/- 4.6 ml/kg/min) and the oxygen consumption (14.6 +/- 4.8 ml/kg/min) corresponding to an increase of arterial lactate level to above the normal value at rest (1.3 mM). The computer program was superior to previously described visual methods for identifying the ventilatory threshold. PMID- 3085464 TI - Comparison of nifedipine alone with propranolol alone for stable angina pectoris including hemodynamics at rest and during exercise. AB - The effects of nifedipine (60 to 90 mg/day) and propranolol (240 mg/day) on symptoms, angina threshold and cardiac function were compared in a placebo controlled, double-blind, crossover study. Five-week treatment periods with nifedipine and propranolol were compared with 2 weeks of placebo treatment in 21 men with chronic stable angina pectoris, 13 of whom had symptoms both at rest and on exertion. Compared with placebo, New York Heart Association functional class improved in patients equally with nifedipine (p = 0.001) and propranolol (p = 0.006). Frequency of chest pain decreased with nifedipine (p = 0.001) and propranolol (p = 0.01), and nitroglycerin consumption similarly decreased with both treatments. Nifedipine significantly delayed the onset of chest pain (p = 0.01) and 1 mm of ST-segment depression (p = 0.002) during bicycle exercise; smaller increases with propranolol were not statistically significant. A preferential clinical response to nifedipine (9 patients) or propranolol (6 patients) was unrelated to the presence or absence of pain at rest or to any baseline hemodynamic finding. Nifedipine and propranolol were equally effective in relieving exertional ischemia as shown by improvements in ejection fraction at identical workloads, from 0.48 +/- 0.11 to 0.58 +/- 0.12 (p less than 0.001) and 0.56 +/- 0.14 (p less than 0.001), respectively. Exercise wall motion, assessed by a semiquantitative wall motion score, also improved with both drugs. Propranolol treatment decreased exercise cardiac output by 14% (p = 0.01) through its effect on heart rate. In contrast, nifedipine treatment had no effect on cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085466 TI - Immunocytochemical studies of pituitary hormones with PAP, ABC, and immunogold techniques: evolution of technology to best fit the antigen. AB - The immunocytochemical technology in our laboratory has evolved in response to specific needs for more efficient, refined stains for each antigen. The rationale for the application of each of the immunocytochemical techniques used today is described, and detailed methods are given. In the early 1970s, it was determined that the peroxidase-antiperoxidase complex (PAP) stain provided the most sensitive means of detection of adrenocorticotropin (ACTH) at the electron microscope level even in tissues prepared with conventional fixation and embedding techniques that are considered rather harsh for the maintenance of antigenicity. Application of the same PAP complex technique to the larger glycoprotein antigens, like follicle-stimulating hormone (FSH), however, proved far more difficult; and the problem was resolved partially when more gentle fixation-embedding protocols were applied. The production of an efficient, reliable stain for FSH was achieved only with the avidin-biotin peroxidase complex (ABC) stains were applied in the early 1980s. This technique also allowed more efficient reactions for all the antigens, and morphometric data could thereby be collected more rapidly. Thus, we concluded that the light microscope immunoperoxidase techniques were excellent for the morphometric analysis of pituitary cell types in both pre-embedding and postembedding stains. However, the need for a more refined stain for its quantification at the electron microscope level on individual organelles led to the development of the colloidal gold stain in 1983-1984. This technique, which is new to our laboratory, is also described and illustrated in this report. Also included is a description of our studies of the effect of fixation and embedding processes on hormone antigenicity and techniques used to control background and nonspecific reactions. It is hoped that the novice will find the description of the rationale for the evolution of technology in our laboratory useful in making choices for his or her own immunocytochemical stains. PMID- 3085467 TI - Nutritional rehabilitation of malnourished patients with cystic fibrosis. AB - We examined the effect of nutritional rehabilitation in cystic fibrosis patients with severe disease. Thirteen malnourished patients (seven males, six females, age 7-27 yr) were studied over 7-16 mo. Oral supplementation was attempted initially in 12 patients (mean duration 6.7 mo); only 2 patients gained weight, 2 withdrew, and 1 died. The remaining 7 patients failed to achieve adequate weight gain and were commenced on nasogastric supplementation with a semisynthetic formula. An additional patient was entered without a prior period of oral supplementation because of the severity of malnutrition. Weight gain was achieved in 7 of 8 patients with nasogastric supplementation (mean duration 6.4 mo). Weight gain was associated with an increase in lean body mass, total body fat, and height velocity. While pulmonary function and biochemical parameters were unchanged, patient well-being improved and episodes of pneumonia decreased. PMID- 3085468 TI - Lysine kinetics at graded lysine intakes in young men. AB - Healthy young men participated in a study designed to explore the effects of decreasing dietary lysine content on plasma amino acid concentrations and lysine kinetics, studied with L-[1-13C]lysine as tracer. Diets provided adequate energy and the equivalent (N X 6.25) of 0.8 g protein kg-1.day-1 as a synthetic L-amino acid mixture simulating egg protein. Lysine intake was reduced every 7 days. Changes in plasma amino acids suggested that effects characteristic of a dietary lysine inadequacy were prevented by consuming more than 32 mg lysine.kg-1 day-1. Primed, continuous intravenous infusions of L-[1-13C]lysine, at the end of each diet period while subjects were in the fed state, showed that as dietary lysine was reduced, 13C enrichment increased in plasma lysine and decreased in expired CO2. It was estimated that lysine oxidation exceeded, by 4.4 mg kg-1 day-1, the lysine intake of 20 mg kg-1.day-1 indicating that the lysine required for body protein maintenance would probably exceed this latter value. These results are discussed in relation to the physiological requirement in adults for lysine, currently accepted to be met by an intake of 12 mg kg-1.day-1. which is assumed to be the upper range of the lysine requirement for this population group. PMID- 3085469 TI - Threonine kinetics at graded threonine intakes in young men. AB - A study was undertaken in eight healthy young men to examine the effects of varying intakes of threonine on plasma free threonine concentrations and threonine kinetics, using a 3 h constant intravenous infusion of L-[1 13C]threonine. Subjects consumed diets based on an L-amino acid mixture, in which the quality of threonine was reduced every 7 days. On the last day of each diet period, determinations of plasma threonine flux and threonine oxidation were carried out while subjects consumed small meals, each supplying 1/12 daily intake, at hourly intervals. Threonine oxidation rates fell with reduced threonine intake, reaching a relatively constant level at intakes of 20 mg.kg 1.day-1 and below. These metabolic data are discussed in relation to the currently established value of 7 mg.kg-1.day-1 as the upper range of the threonine requirement for healthy young adults. It is concluded that actual threonine requirements may be considerably higher for this age group. PMID- 3085470 TI - The immunochemical characterization of the light chains in the mesangial IgA deposits in IgA nephropathy. AB - The immunochemical characterization of the light chains of the mesangial immunoglobulin A (IgA) deposits were studied in 45 patients with IgA nephropathy. Kappa and lambda light chains were detected with direct immunofluorescence (IF) method, using monospecific rabbit anti-human anti-kappa and anti-lambda anti sera. The glomeruli of 42 renal biopsies studied were strongly positive for lambda light chain, while only 25 specimens were positive for kappa light chain. Sixty-five percent of the biopsies showed a predominance of lambda light chain IF staining in the mesangial deposits. This IF pattern is unique as compared with similar studies on renal biopsies from patients with systemic lupus erythematosus, idiopathic membranous nephropathy, and normal postmortem renal tissue. The results indicate that mesangial IgA deposits in IgA nephropathy consist mainly of IgA with lambda light chains despite the fact that the normal ratio of kappa to lambda light-chain-containing immunoglobulin in human serum is two to one. PMID- 3085471 TI - The failure of postinjection Rh immune globulin titers to detect large fetal maternal hemorrhages. AB - The inadequacy of current testing methods for fetal-maternal hemorrhage (FMH) had led to the use of postinjection titers of Rh immune globulin (RhIg) to assess large FMH. The authors have studied the titers of 30 RhIg recipients who received 300 micrograms of RhIg. The 48-hour postinjection titer was compared with the size of bleed as measured by Du testing and the enzyme-linked antiglobulin test (ELAT). Patients had less than 30 mL FMH suggested by negative Du and immune rosette tests. The postinjection titer of RhIg ranged from 0 to 32 when tested by saline-antiglobulin technics. When the size of the bleed was compared with the titer, no correlation could be found. The authors believe that postinjection titers of RhIg should not be used to detect a large FMH. PMID- 3085472 TI - Conjugated bilirubin versus direct bilirubin in neonates. AB - Conjugated and direct bilirubin were measured in 288 samples from 107 neonates less than 15 days old. Retrospective analysis of the medical records showed that 53 neonates were hepatobiliary-normal, 42 patients had no obvious evidence of hepatobiliary disease but had received total parenteral nutrition, and 12 were clearly hepatobiliary-abnormal. Neither the mean values nor the distributions of either the conjugated bilirubin, as measured by a multilayered slide, or the direct bilirubin, measured by a solution diazo procedure, differed when comparing the hepatobiliary-normal population to that receiving total parenteral nutrition. However, as would be predicted, the hepatobiliary-abnormal population differed significantly from both of these groups using either direct bilirubin or conjugated bilirubin results. Samples obtained from hepatobiliary-abnormal neonates were reviewed in chronologic sequence if direct bilirubin results differed from conjugated bilirubin with respect to classification of normality/abnormality. In two of three neonates with developing cholestasis, conjugated bilirubin exceeded its upper limit of normal earlier than did direct bilirubin. Conjugated bilirubin returned to normal earlier than direct bilirubin for two neonates with an improving clinical status. Conjugated bilirubin measurement was judged to be more responsive to developing or resolving cholestasis then direct bilirubin. In addition, conjugated bilirubin measurement from the slide is known to agree well with that determined by high performance liquid chromatography fractionation of bilirubin and is less susceptible to interference than is direct bilirubin measurement, characteristics that recommend its use over direct bilirubin analysis in a clinical setting. PMID- 3085473 TI - Detection of L-forms of Neisseria gonorrhoeae in pure and mixed culture suspensions by an enzyme immunoassay. AB - An enzyme immunoassay (EIA) (Gonozyme, Abbott Laboratories, Chicago, IL) was evaluated for its ability to detect L-forms of Neisseria gonorrhoeae in pure and mixed culture suspensions. A total of 15 L-form strains that were induced from fresh clinical isolates of N. gonorrhoeae on an L-form medium were tested by EIA at antigen levels equivalent to those found in 2 X 10(5), 3 X 10(4), and 2 X 10(3) parental cells per milliliter. The results showed the sensitivity of the EIA for L-forms and parental cells to be the same, exhibiting positive results in all pure culture suspensions of parental cells at 2 X 10(5) and 3 X 10(4) cells per milliliter and their corresponding L-form preparations. At 2 X 10(3) cells per milliliter, three parental and two of their respective L-form preparations yielded positive EIA results. Incorporation of a mixture of heterologous organisms that can be found in the normal human genital flora, each at a concentration of 1 X 10(7) cells per milliliter into the L-form preparations, did not affect the sensitivity of the EIA for detection of L-forms. The results of the present study indicate that the EIA is an equally sensitive method for detecting gonococcal L-forms and parental cells. A further study, however, is needed to ascertain its usefulness under actual clinical conditions. PMID- 3085474 TI - Application of the immunoperoxidase technic to bone marrow trephine biopsies in the classification of patients with monoclonal gammopathies. AB - This study evaluated the utility of the immunoperoxidase method as applied to bone marrow sections in the diagnosis of patients with monoclonal gammopathies. Intracellular immunoglobulin light chains were identified in fixed, decalcified bone marrow biopsy sections from 66 patients with monoclonal proteins, using an avidin-biotin-peroxidase complex immunoperoxidase method. In all cases the predominant light chain identified in the bone marrow biopsy correlated with the monoclonal light chain identified in the serum. In addition, a light chain ratio was defined that correlated with the clinical diagnoses. The light chain ratios were highest in patients with multiple myeloma and were significantly different from those with monoclonal gammopathy of undetermined significance. There was no correlation between level of serum monoclonal protein and light chain ratios. The ratios were also high in patients with macroglobulinemia, primary amyloidosis, and renal disease secondary to monoclonal proteins but without overt myeloma. Determination of light chain ratios differentiated patients with multiple myeloma from those with monoclonal gammopathy of undetermined significance and helped identify patients with end organ damage secondary to monoclonal proteins but without overt myeloma. PMID- 3085475 TI - Immunofixation electrophoresis for identification of IgM paraprotein light chain components. PMID- 3085476 TI - Possible mechanisms of elevation of serum secretory immunoglobulin A in liver diseases. AB - In order to investigate possible mechanisms of elevation of serum secretory immunoglobulin A (sIgA) in liver diseases, human liver specimens were applied to immunohistochemical study of immunoglobulin A, secretory component, and J chain, which are components of sIgA. In the cases of chronic hepatitis with high serum sIgA levels, these antigens were present in dilated bile canaliculi of hepatocytes and they were continuously stained on the lateral plasma membrane of hepatocytes from the bile canaliculus to the space of Disse over the junctional complexes. Furthermore, in liver cirrhosis and extrahepatic cholestasis, they were also detected in intraportal bile ductules and intercellular spaces of degenerated cholangiocytes. These results suggest that at least two pathways might allow elevation of serum sIgA: through the communication of the bile canaliculus with the space of Disse over junctional complexes and through the bile ductule into the portal blood vessel. PMID- 3085477 TI - Intestinal permeability in inflammatory bowel disease. PMID- 3085478 TI - Influence of the poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide on macrophage and granulocyte differentiation of HL-60 cells. AB - We investigated the influence of the poly(ADP-ribose) polymerase inhibitor 3 aminobenzamide (ABA) on induction of phenotypic markers of granulocyte differentiation by retinoic acid and markers of macrophage differentiation by TPA in HL-60 cells. The differentiation of HL-60 cells towards the granulocyte lineage was assessed by hexose monophosphate shunt activity, proportion of cells capable of reducing NBT dye, and the appearance of recognizable neutrophils and bands. The effect of ABA and retinoic acid on NBT dye reduction and appearance of mature neutrophils and bands was synergistic, whereas the effects of these agents on hexose monophosphate shunt activity were additive. The differentiation inducing capacity of ABA in the presence of retinoic acid was dose-related. The influence of ABA on TPA-induced markers of macrophage differentiation was assessed by determining the proportion of adherent cells produced after treatment and by measuring acid phosphatase activity in the adherent cell fraction. In the presence of ABA, the number of cells adhering to plastic declined after day 2 of exposure to TPA, and acid phosphatase activity in adherent cells was inhibited fourfold (p = 0.01). The influence of ABA on the phenotypic markers of granulocyte and macrophage differentiation was detectable at concentrations that were not cytotoxic. The influence of ABA on HL-60 differentiation is similar to that previously reported for human bone marrow CFU-GM. Our data suggest that poly(ADP-ribose) polymerase plays a role in differentiation of HL-60 cells and that HL-60 might provide a useful model for evaluating control mechanisms involved in the differentiation of CFU-GM. PMID- 3085479 TI - Conformational changes in von Willebrand's factor protein: effects on the binding of factor VIII-coagulant. AB - The effects of conformational changes in purified canine von Willebrand's factor (VWF) were investigated to explore the relationship between its factor VIII related antigen (VIII:AG) and ristocetin cofactor (RCoF) properties and the factor VIII-coagulant (VIII:C) binding site(s). Binding of VIII:C from canine von Willebrand's disease (VWD) plasma by VWF was used to measure the combining reaction of these proteins. The VWF was denatured to varying degrees by exposure to temperature and pH extremes, low ionic strength, and 6 M urea. Various treatments resulted in three types of change: elimination of RCoF, VIIIR:Ag, and VIII:C binding, removal of RCoF activity alone; or elimination of RCoF and retarded elution of VIII:Ag and VIII:C. As long as VIIIR:Ag reactivity was maintained, binding of VIII:C could be demonstrated; but in the absence of VIIIR:Ag, neither RCoF activity nor VIII:C binding remained. These results suggest that VIII:C binding and RCoF sites are separate on VWF and that interaction between VIII:C and VWF is possible even after significant structural changes occur in VWF. Furthermore, RCoF is more vulnerable to denaturation than the antigenic site. The spectrum of conformational changes that affect the properties of VWF may parallel the various recognized subtypes of VWD. PMID- 3085480 TI - Plasmapheresis and antiplatelet agents in the treatment of the hemolytic uremic syndrome secondary to mitomycin. AB - Four patients with the hemolytic uremic syndrome secondary to mitomycin therapy were treated with intense plasmapheresis and antiplatelet agents. All four patients had a hematologic response and three had slow, but steady, improvement in renal function. These results suggest an important role for these agents in mitomycin-induced hemolytic uremic syndrome. PMID- 3085481 TI - Distribution of adult lactase phenotypes in the Tuareg of Niger. AB - The adult lactase phenotype, lactose absorber or malabsorber, was determined using the lactose tolerance test with breath hydrogen assay in a group of Tuareg, a traditionally nomadic pastoralist population in the central Sahara. Out of a total of 118 subjects, 103 (87.3%) were lactose absorbers and 15 (12.7%) lactose malabsorbers. The frequency of the "lactase suppression gene" in this population sample was .357 (SD .043). The low frequency of lactase suppression in the Tuareg supports the hypothesis of natural selection in favor of the "lactase persistence gene" in milk-dependent nomadic pastoralist. PMID- 3085483 TI - Cost-effective antimicrobial therapy. PMID- 3085482 TI - Order form improves documentation of administered TNP solutions. PMID- 3085484 TI - Multiple-regression hospitalization-cost model for pharmacy cost analysis. AB - A multiple-regression model that used hospital data for a single diagnosis related group (DRG) was developed and tested as a tool for measuring the effect of pharmaceutical services on costs. Computer-generated data from one university teaching hospital for fiscal year 1983 were used to develop a model for identifying patient-specific and treatment-specific factors that correlated with total hospital costs and adjusted total costs (total costs minus room and board). Costs were analyzed for patients hospitalized for cardiothoracic procedures (DRG 108). Data for 100 patients were included. The demographic, severity, treatment intensity, and drug-use factors included in the model accounted for 95.6% of the variation in adjusted total cost. Length of stay, number of secondary surgical procedures, quantity of supplies or drugs used in the operating room, and several drug therapies--tobramycin, i.v. electrolytes, and i.v. fluids--had significant effects on adjusted total cost. This regression model was useful for assessing the effects of the choice of drug therapy or specific services on the costs for one DRG; it should be tested for other DRGs in other institutions. The usefulness of the model for planning cost-effective services is limited by the need for better billing information, cost-estimation techniques, and records of clinical services provided. PMID- 3085485 TI - Recovery of phenytoin from an enteral nutrient formula. AB - The recovery of phenytoin from phenytoin oral suspension dispersed in an enteral nutrient formula was determined. The study was conducted in two phases. In phase 1, diluted phenytoin oral suspension was added to 10 1-mL samples of full strength Osmolite and 10 1-mL samples of a distilled water control solution to produce a theoretical concentration of 10 micrograms/mL. The samples were filtered through an ultrafiltration membrane and assayed for phenytoin concentration by a homogeneous enzyme-multiplied immunoassay technique. In phase 2, varying amounts of diluted phenytoin oral suspension were added to 30-mL quantities of half-strength Osmolite or control solution to determine the effect of phenytoin concentration on recovery of phenytoin; also, a constant amount of diluted phenytoin oral suspension was added to 30-, 60-, and 90-mL quantities of half-strength Osmolite or control solution to determine the effect of solvent volume on recovery of phenytoin. Duplicate samples of each phase 2 mixture were filtered and assayed in the same manner as phase 1 samples. The mean concentration of phenytoin in phase 1 samples was 3.70 +/- 0.28 microgram/mL for Osmolite and 9.87 +/- 0.27 microgram/mL for control solution; this difference was significant. The percentage of phenytoin recovered from phase 2 samples of Osmolite increased with increasing phenytoin concentration and decreased with increasing volumes of Osmolite. The decreased recovery of phenytoin from the enteral nutrient formula used in this study has potential clinical importance, but further research in humans is needed to substantiate these in vitro observations. PMID- 3085486 TI - Home health-care bibliography. AB - A home health-care bibliography is presented. The bibliography includes a selection of references to descriptive reports, research papers, editorials, letters, and commentaries on home health-care (HHC) services. This bibliography represents important literature from the past 12 years on program planning, marketing, trends, and reimbursement for HHC services as well as specific types of home therapy. The bibliography can be helpful to pharmacy administrators and clinicians who are interested in designing HHC programs or becoming involved in the provision of home therapy. PMID- 3085487 TI - Pharmacy admixture of enteral nutrient products. PMID- 3085488 TI - Effect of diclofenac sodium on the arachidonic acid cascade. AB - The anti-inflammatory activity of nonsteroidal anti-inflammatory drugs is primarily attributed to inhibition of distinct steps in the arachidonic acid cascade, particularly, the cyclo-oxygenase pathway. Diclofenac sodium, a compound of this class of drugs, appears to have a dual effect since it also regulates the lipoxygenase pathway. Study of appropriate cell systems (leukocytes and whole blood in rats) demonstrates that diclofenac's potent inhibition of cyclo oxygenase activity causes a sharp reduction in the formation of prostaglandin, prostacyclin, and thromboxane products, all key mediators of inflammation. Recent work discloses that at higher concentrations, diclofenac sodium also reduces the formation of products of the lipoxygenase pathway (5-hydroxyeicosatetraenoic acid, leukotrienes). The mechanism by which this evolves, however, appears to be unrelated to direct inhibition of lipoxygenase. Instead, by enhancing its reincorporation into triglycerides, diclofenac sodium reduces the intracellular level of free arachidonic acid. PMID- 3085489 TI - The history of diclofenac. AB - The purpose in developing diclofenac sodium was to synthesize a nonsteroidal anti inflammatory drug with high activity and outstanding tolerability. Factors considered were drug transport through biologic membranes, the atomic and spatial structure of the molecule, and the electronic structure. Based on analysis of other nonsteroidal anti-inflammatory drugs, it was postulated that an effective antirheumatic agent should have the following characteristics: an acidity constant between 4 and 5, a partition coefficient of approximately 10, and two aromatic rings twisted in relation to each other. The result was diclofenac sodium, which has an acidity constant of 4.0 and a partition coefficient of 13.4. The structural elements include a phenylacetic acid group, a secondary amino group, and a phenyl ring containing chlorine atoms, which cause maximum twisting of the ring. Experimental and clinical findings obtained to date have indicated that diclofenac sodium was synthesized on well-founded principles. PMID- 3085490 TI - Pharmacology of diclofenac sodium. AB - Diclofenac sodium is the active ingredient in Voltaren, a nonsteroidal anti inflammatory drug designed by selection of appropriate physicochemical and steric properties. Its pharmacologic activity, specifically its effects in acute and subchronic inflammation, and its analgesic activity have been assessed in animal models. The tolerability of the compound as judged by several parameters (i.e., ratio between the acute lethal dose or the dose inducing gastrointestinal blood loss and the desired pharmacologic activity) is favorable in comparison with other nonsteroidal anti-inflammatory drugs. Diclofenac sodium acts by potent cyclo-oxygenase inhibition, reduction of arachidonic acid release, and enhancement of arachidonic acid uptake. It thereby results in a dual inhibitory effect on both the cyclo-oxygenase and lipoxygenase pathways. PMID- 3085491 TI - Hypophysiotropic hormone testing in a patient with hypothalamic hypopituitarism. AB - A 59-year-old woman with metastatic breast carcinoma presented with weight loss, vomiting, and polyuria. Basal endocrine testing revealed low levels of thyroxine, cortisol, and gonadotropins, and the presence of diabetes insipidus. Direct stimulation of the pituitary with hypophysiotropic hormones indicated intact pituitary reserve. Insulin-induced hypoglycemia, however, failed to increase plasma cortisol or growth hormone levels significantly. On computed tomographic scanning, a lesion was found in the area of the hypothalamus. Thus, a functional abnormality of the hypothalamic-pituitary axis causing clinically significant hypothalamic hypopituitarism was not clearly apparent following administration of hypothalamic releasing factors but was demonstrable with indirect stimulation via insulin-induced hypoglycemia. Insulin-induced hypoglycemia remains an important diagnostic test in the evaluation of hypopituitarism. PMID- 3085492 TI - Enteral nutrition in patients receiving mechanical ventilation. Multiple sources of tracheal colonization include the stomach. AB - Nutritional therapy of patients receiving mechanical ventilation includes enteral feeding. To determine the frequency of gastric microbial colonization in patients receiving enteral nutrition, 18 patients with acute respiratory failure receiving ventilation were studied. Multiple sources of tracheal colonization were then evaluated to determine the frequency of tracheal transmission of gastric flora and the relationship of gastric colonization and transmission to nosocomial respiratory infection. The stomach was colonized in every patient who received enteral feeding. Tracheal colonization occurred in 89 percent (16 of 18) of patients. In 12 of these 16 patients, 14 organisms colonized the trachea after transmission from the stomach and/or oropharynx. Thirty-six percent (five of 14) of organisms transmitted to the trachea originated from the stomach, whereas another 36 percent (five of 14) were first recovered from the oropharynx. Four tracheally transmitted organisms were first recovered simultaneously from the stomach and oropharynx. Nosocomial respiratory infection developed in 11 patients (63 percent). Three infections occurred during the six-day study period, one of which was associated with transmission of a gastric organism. Multiple sources of tracheal colonization occur in patients receiving enteral nutrition. The stomach is an important source of tracheal colonization. Enteral nutrition can be associated with gastric flora colonizing the trachea and causing nosocomial respiratory infection. PMID- 3085493 TI - Use of the erythrocyte sedimentation rate in chronically ill, elderly patients with a decline in health status. AB - A decline in health status in a chronically ill, elderly patient could mean the progression of a known disease, depression, or the development of a new disease. The value of the erythrocyte sedimentation rate in selecting patients in whom the likelihood of a new disease is high enough to warrant a diagnostic evaluation was studied. Subjects included long-term residents of a chronic-care hospital over age 65 in whom the erythrocyte sedimentation rate was determined because of a nonspecific, subacute change in health status (n = 98) or new, unexplained musculoskeletal complaints (n = 44). The target erythrocyte sedimentation rate elevating diseases included infections, connective tissue diseases, and malignancies. Among the group with subacute deterioration, post-test probabilities (incorporating clinical data with test results) of a new disease ranged from 7 percent in those with an erythrocyte sedimentation rate below 20 mm per hour to 66 percent in those with a rate of 50 mm per hour or more. The comparable probabilities among the group with musculoskeletal complaints were 3 percent and 57 percent. The erythrocyte sedimentation rate, an inexpensive test, although nonspecific, appears useful in deciding when to pursue expensive, and sometimes uncomfortable or hazardous, diagnostic evaluations. The erythrocyte sedimentation rate is most useful among patients in whom the probability of disease is moderate (neither very high nor very low) following initial history taking and examination. PMID- 3085494 TI - Sarcoidosis and immunocytoma. AB - The current literature contains reports of sarcoidosis with polyclonal increases in immunoglobulins. There are also reports of lymphoma in patients with pre existing sarcoidosis. This is believed to be the first report of a patient in whom a monoclonal IgM kappa paraproteinemia developed after the diagnosis of sarcoidosis. This paraproteinemia was linked with a histologically proved non Hodgkin's lymphoma. The possible relationships between the two disease entities are discussed. PMID- 3085495 TI - New therapies for the chronic complications of older diabetic patients. AB - Recently, four biochemical mechanisms have been implicated in the pathogenesis of certain late complications of diabetes mellitus. All of these mechanisms (altered polyol pathway activity, disrupted myo-inositol metabolism, increased vascular permeability, and increased nonenzymatic glycosylation of proteins) are activated by exposure of tissues to hyperglycemia. There is evidence to suggest that the development of retinopathy, nephropathy, and neuropathy is directly related to the level of glycemia in patients with diabetes mellitus. Whether strict glycemic control will prevent or reverse diabetic complications is the subject of the Diabetes Control and Complications Trial. Until the results of that study are reported, and until euglycemia can be achieved in all diabetic patients, the search will continue for other pharmacologic agents that might prevent the development of complications. Therapies that are currently under investigation include administration of aldose reductase inhibitors and supplementation of dietary myo-inositol. It is too early to conclude whether such therapies will prove useful in the prevention or reversal of diabetic complications. PMID- 3085496 TI - Hemoglobin production in human bone marrow cultures is inhibited by lyophilized coagulation factor concentrates. AB - Transfusion of blood products may be followed by viral hepatitis and aplastic anemia despite improved techniques for prevention. In view of the need for intensive therapy of hemophilia with blood products, the authors investigated the capacity of these concentrates to influence cultures of human bone marrow cells. Factor VIII concentrates contained a heat-stable dialyzable substance(s) that drastically impaired 59Fe incorporation in normal human bone marrow. Factor IX concentrates had less and cryoprecipitate had no such inhibitory activity. These studies may offer information regarding the effects of various blood products on bone marrow function. PMID- 3085497 TI - Plasma lipids and apolipoproteins in a 13-year-old boy with diabetic ketoacidosis and extreme hyperlipidemia. AB - A 13-year-old boy with untreated diabetes presented in severe ketoacidosis (DKA) for the first time with an initial triglyceride (TG) level of 14,461 mg/dl. Serial blood samples were drawn to determine the interrelationships of changes in lipids and apolipoproteins during treatment with insulin and intravenous fluids. The TG level declined to 122 mg/dl in 7 days concomitant with a lowering of apolipoproteins C-II, C-III, E, D, and F. Further observations suggested that the TG-rich lipoproteins underwent degradation associated with a decline in the levels of apolipoproteins associated with very low density lipoprotein (VLDL) in contrast to an increase in high density lipoprotein-cholesterol (HDL-C), ApoA-I and ApoA-II. ApoB and low density lipoprotein cholesterol (LDL-C) were increased transiently. Subsequent therapy with continuous subcutaneous insulin infusion (CSII) were effective in maintaining glucose homeostasis and normolipidemia for 6 months. PMID- 3085498 TI - An autosomal recessive mental retardation syndrome with hepatic fibrosis and renal cysts. AB - Two sisters had developmental retardation and congenital hepatic fibrosis. One, 23 years old, had facial anomalies reminiscent of Smith-Lemli-Opitz syndrome, ocular coloboma, and hypoplastic kidneys with a single cyst. The other sister died at 18 months and had an encephalocele and cystically dilated collecting ducts in the renal medulla. Although the manifestations in these two sisters are similar to the Smith-Lemli-Opitz and Meckel syndromes respectively, there are sufficient differences to suggest that they had a separate autosomal recessive MCA-MR syndrome. PMID- 3085500 TI - Persistent hyperplastic primary vitreous and recessive oculo-dento-osseous dysplasia. AB - We report on a patient with oculo-dento-osseous dysplasia and bilateral persistence of the hyaloid system. Autosomal recessive inheritance may be the cause of this patient's condition since she was born to unaffected first-cousin parents. Ocular findings in the recessive variety of this syndrome seem to be more severe than those in the more common dominant form. PMID- 3085499 TI - Concurrence of von Willebrand's disease and hemophilia A: implications for carrier detection and prevalence. AB - Five families with concurrent von Willebrand's disease (VWD) and classic hemophilia (hemophilia A) are described. Three were ascertained through women undergoing hemophilia carrier testing, one through an obligate carrier who also has VWD, and one through the affected father of a hemophiliac. The VWD probands exhibited Type I VWD with reduced Factor VIII-related antigen (VIIIR:Ag) and/or von Willebrand factor on more than one occasion, normal VIIIR:Ag on crossed immunoelectrophoresis, and mild symptoms. No male had both disorders, but two obligate hemophilia carriers also had VWD. Neither was detectable as a carrier by discriminant analysis. Four possible carriers of hemophilia had VWD and would also be classified as noncarriers statistically. These findings suggest that the presence of VWD may invalidate hemophilia carrier testing by conventional methods. The independent entry into the family of the two genes by mating of a hemophilia carrier and a VWD male is documented in two cases and probable in two. The observed frequency of such matings supports the hypothesis that VWD is a common disorder. PMID- 3085501 TI - Therapeutic drug monitoring in patients with chronic renal failure: evaluation of the Abbott TDx drug assay system. AB - Immunoassay techniques have been widely used for therapeutic drug monitoring, but lack of antibody specificity can lead to measurement of erroneous drug concentrations due to cross-reactivity with other drugs, metabolites, or endogenous substances, particularly in patients with excretory organ compromise such as renal dysfunction. The Abbott TDx system, a popular automated immunoassay method for therapeutic drug monitoring, was used to measure apparent serum concentrations of carbamazepine, digoxin, gentamicin, lidocaine, phenobarbital, phenytoin, quinidine, valproic acid, and vancomycin in patients with renal failure who were not receiving these drugs. Endogenous substances and other concomitantly administered drugs did not lead to spuriously elevated drug levels, and a previous report of cross-reactive digoxin-like substances was not confirmed. Pooled plasma samples from the patients were spiked with digoxin or phenytoin, each at two concentrations, and the samples were assayed for the drug concentration using the TDx system. No falsely elevated values were found. This work suggests that the TDx system may be better suited for the measurement of these drugs in patients with renal failure than some other immunoassay methods. PMID- 3085502 TI - Cardiovascular alterations in severe pregnancy-induced hypertension: effects of intravenous nitroglycerin coupled with blood volume expansion. AB - Control of blood pressure in severe pregnancy-induced hypertension has often relied on agents with an unpredictable onset and duration of action. Because intravenous nitroglycerin is a potent, rapidly acting agent with a hemodynamic half-life measured in minutes, we evaluated its cardiovascular effects with and without volume expansion in six patients with severe pregnancy-induced hypertension. Nitroglycerin alone reduced mean arterial pressure by 27.5% without any significant changes in heart rate, central venous pressure, or stroke volume. The pulmonary capillary wedge pressure fell from 9 +/- 3 to 4 +/- 2 mm Hg (p less than 0.05) while the cardiac index decreased from 3.51 +/- 0.67 to 2.87 +/- 0.76 L/min X m2. Oxygen delivery fell significantly (p less than 0.05), from 617 +/- 78 to 491 +/- 106 ml/min X m2. While volume expansion alone had no effect on mean arterial pressure, the combination of blood volume expansion and nitroglycerin resulted in a marked resistance to the hypotensive effect of nitroglycerin. Cardiac index, pulmonary capillary wedge pressure, and oxygen utilization were not significantly different from baseline values when volume expansion preceded nitroglycerin. We conclude that the ease with which nitroglycerin reduces blood pressure is dependent on the individual patient's volume status. Although volume expansion allows one to maintain cardiac index, pulmonary capillary wedge pressure, and oxygen utilization when used in combination with nitroglycerin, this benefit may be offset by a concomitant reduction in hypotensive capability. PMID- 3085503 TI - Ultrasound-guided fetal intravascular transfusion in severe rhesus immunization. AB - The successful use of ultrasound-guided fetal umbilical venipuncture and direct intravascular transfusion in a case of severe hydrops fetalis at 28 weeks' gestational age is described. Complete reversal of the hydropic changes was observed in utero. The use of this new technique in fetal treatment of Rh disease is discussed. PMID- 3085504 TI - Relationship of gonadotropin-releasing hormone, danazol, and prostaglandin blockade to ovarian enlargement and ascites formation of the ovarian hyperstimulation syndrome in the rabbit. AB - The effects of pharmacologic doses of gonadotropin-releasing hormone, danazol, and indomethacin on the clinical and endocrinologic features of the ovarian hyperstimulation syndrome were studied in the rabbit. The ovarian hyperstimulation syndrome was induced with Pergonal (75 IU of follicle stimulating hormone and 75 IU of luteinizing hormone) and a follicle-stimulating hormone-dominant gonadotropin preparation (85 IU of follicle-stimulating hormone and 53 IU of luteinizing hormone). None of the three agents tested were effective in suppressing the ovarian enlargement and ascites formation in these animals. Ascites developed despite quite significant variations in plasma and intraovarian sex steroid hormone and intraovarian prostaglandin F levels induced by danazol and indomethacin. Ascites develops in hyperstimulated women in association with both follicular and luteal hyperstimulation. In contrast, the ascites response in the hyperstimulated rabbit develops in the presence of follicular hyperstimulation alone without a significant degree of luteal hyperstimulation. PMID- 3085505 TI - Tumor markers in ovarian cancer: a comparison between immunosuppressive acidic protein and alpha 1-acid glycoprotein. PMID- 3085506 TI - Lupus anticoagulant and pregnancy. PMID- 3085507 TI - An obstetric approach to the prevention of early-onset group B beta-hemolytic streptococcal sepsis. AB - Group B beta-hemolytic streptococcus is one of the most common causes of neonatal sepsis. Despite its relationship to neonatal morbidity and mortality, no consensus exists for an approach to its prevention. Several characteristics of the organism such as high maternal carriage rates, the intermittent nature of this carriage, and the failure of antibiotics to permanently eliminate carriage have limited the success of proposed intervention protocols. In this clinical opinion we review characteristics of the organism and previously suggested intervention protocols. Then, based on this review and an analysis of recently published data, a protocol focusing on preterm births is presented. This proposal favors intrapartum treatment of all mothers who are delivered of preterm infants and who are either carriers of group B beta-hemolytic streptococci or whose carriage status is unknown. A comparison of the costs and benefits of this and other approaches is made. PMID- 3085508 TI - Physiologic changes in pregnant women and their fetuses during jet air travel. AB - The physiologic reactions of pregnant women and their fetuses were studied during routine commercial flights. Ten healthy pregnant women (32 to 38 weeks of gestation) each undertook two flights. Maternal respiratory and heart rates, transcutaneous PO2 and PCO2, blood pressure, uterine activity, and fetal beat-to beat heart rate variability were continuously monitored. During these flights, maternal heart rate and blood pressure increased, and PO2 decreased significantly while PCO2 remained unchanged. Respiratory rate showed a short increase during takeoff and landing but remained unchanged during the rest of the flight. Mean fetal heart rate was within normal limits during the whole flight. No bradycardia, prolonged tachycardia, or significant loss of heart rate variability was observed. This study indicates no hazards of commercial flights to the mother and the fetus in uncomplicated pregnancies. PMID- 3085509 TI - Immunopathology of Hodgkin's disease. Characterization of Reed-Sternberg cells with monoclonal antibodies. AB - The cellular origin of the Reed-Sternberg cells of Hodgkin's disease is controversial. The authors studied 14 cases of Hodgkin's disease (nodular sclerosis, 9; mixed cellularity, 3; lymphocyte predominant, 2), utilizing a panel of 16 monoclonal antibodies, including 5 new monoclonal antibodies defining differentiation antigens of the monocyte/macrophage system. Reed-Sternberg cells were found to react with antibodies to Ia-like (HLA-DR) determinants (14 of 14 cases), Leu M1, an antigranulocyte antibody (11 of 14 cases), and rarely B-1, an antibody defining an antigen expressed on human B lymphocytes (2 of 14 cases). Reed-Sternberg cells did not react with any of 5 antibodies to differentiation antigens of the monocyte/macrophage system (MoP9, MoS39, MoR17, MoU26, MoU50). In contrast, reactive histiocytes in the Hodgkin's disease infiltrates stained strongly. The findings are evidence against the monocyte-macrophage origin of Reed-Sternberg cells and support the view that the Reed-Sternberg cells of Hodgkin's disease derive from other cell types, such as interdigitating reticulum cells, or as yet uncharacterized cells which do not share antigens of the monocyte/macrophage system. PMID- 3085510 TI - Leu 7 immunoreactivity in fetal olfactory epithelium and dysplastic or neoplastic olfactory lesions induced in Syrian golden hamsters by N-nitrosodiethylamine. AB - The biotinylated monoclonal IgM antibody, anti-Leu 7 (HNK-1) was used to localize, by 2-step avidin-biotin immunocytochemistry, an antigen that appears in olfactory nasal epithelium of male Syrian Golden hamsters during N nitrosodiethylamine (DEN) carcinogenesis. In normal young adult and adult hamsters, Leu 7 was not immunoreactive with nasal olfactory epithelium. In hamsters that had been given multiple doses of DEN, Leu 7 immunoreactivity was found throughout the olfactory epithelium. The carcinogen produced dysplastic and hyperplastic lesions in the olfactory epithelium as well as carcinoma in situ and poorly differentiated carcinomas, occasionally with rosette-like structures, all of which were immunoreactive with the Leu 7 monoclonal antibody. Other preneoplastic lesions and tumors (adenomas of nasal glands, papillomas, adenocarcinomas) in olfactory and respiratory nasal epithelium were never immunoreactive. Hamster fetuses expressed Leu 7 diffusely on olfactory epithelial cell membranes, neonatal hamsters had much less antigen, and 14- and 28-day-old hamsters contained few immunoreactive cells. Thus, evidence was provided that Leu 7 reacts with a fetal olfactory antigen which reappears during stages of chemically induced nasal carcinogenesis in Syrian Golden hamsters. PMID- 3085511 TI - Isolation and characterization of alpha 1-antitrypsin in PAS-positive hepatic granules from rats with experimental alpha 1-antitrypsin deficiency. AB - Chronic galactosamine (GalNH2) administration in rats decreases plasma alpha 1 antitrypsin (AAT) levels to 10-50% of control levels and induces the formation of diastase-resistant, PAS-positive granules, which contain AAT in hepatocytes. This report describes the isolation and purification of hepatic granule AAT by three different methods: solubilization with guanidine hydrochloride followed by gel filtration on Bio-gel A5M, extraction with methylamine and 2-chloroethanol, and solubilization with sodium dodecyl sulfate (SDS) followed by preparative SDS polyacrylamide gel electrophoresis. All three methods yield a single protein which precipitates with anti-rat plasma AAT antibody, and which has an apparent molecular weight of 45,000 daltons, in contrast to the molecular weight of plasma AAT, 50,000 daltons. Unlike plasma AAT, granule AAT contains no sialic acid, galactose, or fucose. Moreover, granule AAT contains a reduced amount of N acetylglucosamine and an increased amount of mannose, compared with plasma AAT. The carbohydrate content of granule AAT varies with the isolation procedure used. Granule AAT is susceptible to cleavage by endoglucosaminidase H, which indicates the presence of high-mannose type oligosaccharides. Comparison of the molecular weight, carbohydrate composition, isoelectric point, and endoglucosaminidase H sensitivity of granule AAT isolated from rats with GalNH2-induced AAT deficiency with granule AAT from PiZ humans extends the list of similarities between experimental GalNH2-induced AAT deficiency in rats by and genetically determined AAT deficiency in humans. PMID- 3085512 TI - Influence of surface pH on intracellular pH regulation in cardiac and skeletal muscle. AB - The influence of the surface pH (pHs) on the intracellular pH (pHi) and the recovery of pHi after an imposed intracellular acid load was investigated in isolated sheep cardiac Purkinje fiber, rabbit papillary muscle, and mouse and rat soleus muscle. pHs and pHi, respectively, were continuously measured by use of single- and double-barreled pH-sensitive glass microelectrodes. Surface acidosis, usually obtained by superfusion with solutions of acid pH, was also produced with low buffered (5 mM N-2-hydroxyethylpiperazine-N'-2-ethane-sulfonic acid) solutions at control pH. The pHs decrease (delta pHs) induced by low buffering was smallest (-0.08 pH unit) in Purkinje fiber and largest (-0.31 pH unit) in rat soleus muscle, which already had a more acid surface in control conditions. delta pHs was somewhat dependent on the superfusion rate. Higher superfusion rates decreased but did not abolish delta pHs. Surface acidosis was associated with a small intracellular acidification. Intracellular acid loads were produced by adding and subsequently withdrawing 20 meq/l NH4+ from the superfusate. In all preparations, the rate of recovery of pHi after NH4+ withdrawal was notably decreased at acidified pHs. This effect was amiloride sensitive. It is concluded that, in superfused multi-cellular preparations, pHs and therefore the buffer concentration of a superfusate can considerably influence steady-state pHi and pHi recovery from an imposed intracellular acid load. PMID- 3085513 TI - Calcium transients and resting levels in isolated smooth muscle cells as monitored with quin 2. AB - The Ca2+-sensitive dye quin 2 was used to monitor Ca2+ levels and to follow Ca2+ transients in suspensions of isolated toad (Bufo marinus) smooth muscle cells, whose contractile activity was monitored with a Coulter counter. Single cells were not utilized to follow Ca2+ changes involved with contraction because of problems of rapid dye bleaching and due to photosensitization of smooth muscle cells loaded with quin 2. High levels of quin 2 loading (2-5 mM) severely prolonged (time course increase greater than 3 times), or completely inhibited, contractile responses to carbachol or potassium depolarization. Lower levels (less than 1 mM) produced adequate fluorescent signals, even at the single cell level, and allowed contractile responses of normal magnitude, although with somewhat prolonged (2-3 times) time course. Resting Ca2+ concentrations determined using quin 2 at these lower levels were 129 +/- 3 nM, a value that closely coincided with that measured in the same cell type using Ca-sensitive microelectrodes, or an alternate, more highly fluorescent dye, Fura-2. Resting Ca2+ was highly dependent on the extracellular Ca2+ concentration that appeared to effect intracellular Ca2+ (Cai2+) both by altering the driving force on Ca2+ cross the membrane, as well as the Ca2+ permeability of the cell itself. A small but significant relaxation was observed in response to the lowering of cytoplasmic Ca2+ below resting levels. After carbachol or K+ addition, fluorescent transients peaked significantly before the onset of contraction, which was also transient. Isoproterenol, a known relaxant of these cells, caused a small decrease in Cai2+ (approximately 40 nM) below rest, when applied in maximal dosage (10(-4) M). Isoproterenol also consistently diminished the Ca2+ transient induced by excitatory stimuli such as carbachol or K+. These results indicate that changes in contractility may be directly linked to changes in free cytoplasmic Ca2+ in smooth muscle cells. PMID- 3085514 TI - Inositol trisphosphate enhances calcium release in skinned cardiac and skeletal muscle. AB - Experiments from other laboratories suggest that inositol trisphosphate (InsP3) may be involved in the excitation-contraction coupling (ECC) process of cardiac and skeletal muscle. Our results support this hypothesis. Studying fiber bundles (less than 200-microns diameter) from guinea pig papillary muscles skinned with saponin and mechanically skinned single fibers from frog semitendinosus muscle, we find that calcium-induced force oscillations (observed in solutions containing low ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid and pCa 7.0) are enhanced in magnitude and frequency by InsP3 at concentrations as low as 1 microM. InsP3 at 10 microM can often induce such oscillations in mechanically skinned frog skeletal muscle. In skinned cardiac fibers, InsP3 increases the magnitude of caffeine contractures at submaximal caffeine concentrations to a greater extent than at near-maximal caffeine concentrations. InsP3 (30 microM) has no effect on either the calcium sensitivity or maximal force generated by the contractile apparatus of skinned cardiac muscle. We conclude that InsP3 has no direct effect on the contractile machinery but that it can modulate ECC by enhancing the calcium-induced release of calcium from the sarcoplasmic reticulum, possibly from the same pool and through the same mechanism as caffeine. PMID- 3085515 TI - Insulin metabolism by liver, muscle, and kidneys from spontaneously diabetic rats. AB - The in vivo metabolism of insulin is a complex process in which liver, kidney, and muscle are major participants. In this study we evaluated the effect of spontaneous hyperglycemic nonketoacidotic diabetes (DH) and ketoacidotic diabetes (DKA) on insulin clearance and degradation by these organs. Livers, hindlimbs, and kidneys from nondiabetic controls and DH and DKA Bio-Breed rats were isolated and perfused with artificial media. Liver clearance of immunoreactive insulin (ml/min) was significantly higher in DH rats, 6.0 +/- 0.2, but significantly lower in DKA rats, 3.4 +/- 0.5, compared with controls, 4.6 +/- 0.2. Acidosis alone induced by ammonium chloride loading, did not impair liver insulin clearance (4.8 +/- 0.4 ml/min). Muscle responded differently to the diabetic state in that insulin clearance was not altered by DH and DKA. Renal (organ) clearance of insulin was significantly depressed in the DKA state when compared with controls (0.52 +/- 0.04 and 0.75 +/- 0.07 ml X min-1 X g-1, respectively). This could largely be explained by a lower glomerular filtration rate. Fractional urinary insulin clearance was increased twofold above control values in DH kidneys and fourfold in DKA kidneys, indicating that tubular luminal absorption of insulin was impaired in both states. By contrast contraluminal uptake (peritubular clearance) did not differ significantly from controls. 125I-insulin degrading activity of the 100,000 g supernate fraction from muscle homogenates was similar in the diabetic and control groups. However in liver and kidney, degrading activity did not correspond to whole organ insulin clearance in a consistent manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085516 TI - Effect of systemic acid-base disorders on ileal intracellular pH and ion transport. AB - We previously reported that changes in ileal net Na absorption correlated with arterial pH, changes in net HCO3 secretion correlated with the plasma HCO3 concentration, and changes in net Cl absorption correlated with arterial CO2 partial pressure (PCO2) during the systemic acid-base disorders. To determine whether changes in intracellular pH (pHi) and HCO3 concentration [( HCO3]i) mediated these effects, we measured pHi and calculated [HCO3]i in the distal ileal mucosa of anesthetized, mechanically ventilated Sprague-Dawley rats using 5,5-[14C]dimethyloxazolidine-2,4,-dione and [3H]inulin. Rats were studied during normocapnia, acute respiratory acidosis, and alkalosis, and uncompensated and pH compensated acute metabolic acidosis and alkalosis. When animals in all groups were considered, mucosal pHi was not altered, but there were strong correlations between mucosal [HCO3]i and both arterial PCO2 (r = 0.97) and [HCO3] (r = 0.61). When we considered the rates of ileal electrolyte transport that characterized these acid-base disorders [A. N. Charney and L.P. Haskell, Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G230-G235, 1983], we found strong correlations between mucosal [HCO3]i and both net Cl absorption (r = 0.88) and net HCO3 secretion (r = 0.82). These findings suggest that the systemic acid-base disorders do not affect ileal mucosal pHi but do alter mucosal [HCO3]i as a consequence of altered arterial PCO2 and [HCO3]. The effects of these disorders on ileal net Cl absorption and HCO3 secretion may be mediated by changes in [HCO3]i. Arterial pH does not appear to alter ileal Na absorption through changes in the mucosal acid-base milieu. PMID- 3085517 TI - Measurements of intracellular pH in Necturus antral mucosa by microelectrode technique. AB - Intracellular pH (pHi) was measured in the surface epithelial cells of Necturus antrum using pH-sensitive intracellular microelectrodes. Electrodes were prepared by filling 10- to 20-M omega resistance glass microelectrodes with a H+ ion selective exchange resin and calibrated before use in solutions of known pH 4.0 8.0. The electrode response (n = 15) was linear (r = 0.93; P less than 0.001) with a slope of 52.1 +/- 2.3 mV/pH unit. Antral mucosa was mounted in a modified Ussing chamber and pHi was determined from the difference between the potentials recorded by intracellular H+-selective and conventional microelectrodes. These measurements of pHi were validated by examining the response of the intracellular microelectrodes to 1) depolarization of the cell membrane produced by K+ substitution for Na+, and 2) alkalinization and acidification of pHi produced by NH+4 substitution for Na+ in the bathing solutions. In tissues bathed with HCO-3 Ringer solution (pH 7.0), the mean pHi was 7.34 +/- 0.02 with a range from 7.24 to 7.43. In N-2-hydroxymethylpiperazine-N' -ethanesulfonic acid (HEPES)-Ringer solution (pH 7.0), pHi was reduced to 7.02 +/- 0.05 (P less than 0.01). Acidification of the luminal solution to pH 6.8 with CO2 produced a 0.22 +/- 0.04 pH unit fall in pHi (P less than 0.001). In contrast, acidification to pH 4.0 with HCl had no significant effects on pHi. These findings indicate that HCO-3 may play an important role in pHi regulation in this tissue. In addition, they suggest that, in contrast to CO2, the surface epithelial cells of Necturus antrum are relatively resistant to acidification by luminal HCl. PMID- 3085518 TI - Sites of resistance changes with inhibition of acid secretion in frog stomach. AB - The primary purpose of this study was to determine the sites of resistance changes from thiocyanate inhibition of secretion to better evaluate models of the gastric proton pump. The potential difference, resistance, and H+ secretory rate were measured with various tonicities of the secretory fluid. Thiocyanate (SCN) inhibition generally produces a resistance increase, but with nutrient Ba, the resistance is high and SCN decreases it. The latter effect is also seen with cimetidine. In the secreting fundus a hypotonic secretory solution has a small effect on resistance, but in the inhibited fundus the effect is huge, due to increase of resistance of the lumen-tubular cell pathway. With a hypotonic secretory solution, for inhibited fundus (cimetidine or omeprazole) and antrum, SCN does not decrease the resistance of the surface cells and/or the transintercellular pathways with or without Ba. The SCN resistance decrease with Ba is via the tubular cell pathway. With Ba the resistance of the nutrient membrane of the tubular cells decreases after SCN or cimetidine inhibition. The findings further support the concept that under standard conditions the resistance via the lumina and tubular cells is low and that via the surface cells and transintercellular pathways is high. PMID- 3085519 TI - Dynamic response of PG synthesis to peptide hormones and osmolality in renal tubular cells. AB - A superfusion technique was adapted to collagenase-dispersed renal medullary and cortical tubular cells to study prostaglandin (PG) synthesis in response to arginine vasopressin (AVP), angiotensin II (ANG II), bradykinin (BK), Ca2+ ionophore A23187, and to changes in osmolality. Medullary and cortical cells promptly responded to the stimuli by an increase in PGE2 and PGF2 alpha production, whereas 6-keto-PGF1 alpha was not detected. AVP and BK were active on medullary cells, and ANG II was active mainly on cortical cells. A23187 stimulated PG synthesis in both cells but predominantly in the medulla. PG synthesis was dependent on the presence of extracellular Ca2+. The Ca2+ entry blocking agents verapamil and lanthanum did not inhibit the PG response to AVP, BK, and ANG II. Thus peptide hormone-stimulated PG synthesis in renal tubular cells did not depend on Ca2+ influx through channels blocked by these agents. Hyperosmolar NaCl or mannitol stimulated PG synthesis in cortical and, more markedly, in medullary cells. Hyperosmolar urea inhibited PGE2 synthesis stimulated by peptide hormones, NaCl, and A23187 in both cell preparations. In conclusion, the superfusion of isolated tubular cells is a useful method to study the dynamic aspects of renal PG release in response to various sequentially applied stimuli. PMID- 3085520 TI - Oxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle. AB - Experiments were designed to determine the role of oxygen-derived free radicals in modulating contractions of vascular smooth muscle and endothelium-mediated relaxations to acetylcholine. The effects of generating or scavenging these radicals were studied in rings of canine coronary arteries suspended for isometric tension recording. Xanthine oxidase plus xanthine caused relaxations, which were greater in rings with endothelium than in rings without endothelium; the relaxations were not affected by superoxide dismutase or mannitol, but could be prevented by catalase. Xanthine oxidase plus xanthine depressed endothelium mediated relaxations to acetylcholine; this effect was prevented by superoxide dismutase, but was not affected by catalase or mannitol. Exogenous hydrogen peroxide induced catalase-sensitive relaxations, which were depressed by the removal of the endothelium. Superoxide dismutase evoked catalase-sensitive relaxations only in rings with endothelium. Endothelium-mediated relaxations to acetylcholine were slightly depressed by superoxide dismutase or catalase alone; the combination of the two enzymes or mannitol caused a major shift to the right of the concentration-response curve to acetylcholine. In rings without endothelium, relaxations caused by sodium nitroprusside were not affected by the scavengers (alone or in combination) but were augmented by xanthine oxidase plus xanthine. These data suggest that the endothelium-derived relaxing factor released by acetylcholine is not likely to be an oxygen-derived free radical; hydrogen peroxide has a direct inhibitory action on coronary arterial smooth muscle and triggers endothelium-dependent relaxations; and superoxide anions depress and hydroxyl radicals facilitate endothelium-dependent relaxations caused by activation of muscarinic receptors. PMID- 3085522 TI - Source of admission and cost: public hospitals face financial risk. AB - We studied all admissions to the 11 acute care hospitals of the New York City Health and Hospitals Corporation (April 1983-September 1984) matching emergency room (ER) admitted diagnostic related group (DRG) subgroups in each hospital with at least five non-ER admitted patients (N = 222,961). Mean cost per ER patient ($8,385) was greater than non-ER mean cost per patient ($4,386) for Medicare and non-Medicare. Our data suggest that public hospitals with a high proportion of ER admissions may be at a financial disadvantage under DRG reimbursement. PMID- 3085521 TI - Energy expenditure by doubly labeled water: validation in humans and proposed calculation. AB - To further validate the doubly labeled water method for measurement of CO2 production and energy expenditure in humans, we compared it with near-continuous respiratory gas exchange in nine healthy young adult males. Subjects were housed in a respiratory chamber for 4 days. Each received 2H2(18)O at either a low (n = 6) or a moderate (n = 3) isotope dose. Low and moderate doses produced initial 2H enrichments of 5 and 10 X 10(-3) atom percent excess, respectively, and initial 18O enrichments of 2 and 2.5 X 10(-2) atom percent excess, respectively. Total body water was calculated from isotope dilution in saliva collected at 4 and 5 h after the dose. CO2 production was calculated by the two-point method using the isotopic enrichments of urines collected just before each subject entered and left the chamber. Isotope enrichments relative to predose samples were measured by isotope ratio mass spectrometry. At low isotope dose, doubly labeled water overestimated average daily energy expenditure by 8 +/- 9% (SD) (range -7 to 22%). At moderate dose the difference was reduced to +4 +/- 5% (range 0-9%). The isotope elimination curves for 2H and 18O from serial urines collected from one of the subjects showed expected diurnal variations but were otherwise quite smooth. The overestimate may be due to approximations in the corrections for isotope fractionation and isotope dilution. An alternative approach to the corrections is presented that reduces the overestimate to 1%. PMID- 3085523 TI - Leu-M1 antigen in human neoplasms. An immunohistologic study of 400 cases. AB - Several studies have shown that the Leu-M1 antigen, a monocyte/granulocyte related marker, is consistently expressed by the neoplastic cells of patients with Hodgkin's disease (HD). It has been suggested that reactivity of Reed Sternberg cells with Leu-M1 can be used in support of a morphologic interpretation of HD, and that it is helpful in the differential diagnosis of HD from morphologically similar lesions. To evaluate the significance of the Leu-M1 positivity of Reed-Sternberg cells in the diagnosis of HD, we investigated the distribution of Leu-M1 antigen in a series of patients with HD, non-Hodgkin's lymphomas, and nonhematopoietic neoplasms. We were able to demonstrate the presence of Leu-M1 antigen not only in the majority of patients with HD, but also in 12 of 18 (67%) peripheral T-cell lymphomas, as well as in a variety of nonhematopoietic neoplasms, which included 113 of 199 carcinomas, most of them (58%) adenocarcinomas. Only one of 34 sarcomas showed a focal positive reaction. Leu-M1-related antigen was not detected in any of 18 mesotheliomas, 15 germ cell tumors, 13 melanomas, three schwannomas, or three astrocytomas. Our study indicates that Leu-M1 positivity has no value in supporting the diagnosis of HD in situations where the histologic diagnosis of HD is doubtful. However, since anti-Leu-M1 reacted positively in the majority of adenocarcinomas but was absent in mesotheliomas, melanomas, and most sarcomas, this antigen could serve as a new marker that may be helpful in situations in which carcinoma is a part of the differential diagnosis. PMID- 3085524 TI - The man behind Lafora's bodies. PMID- 3085525 TI - Experimental Schistosoma mansoni infection in a small New World monkey, the saddle-back tamarin (Saguinus fuscicollis). AB - Twelve young adult captivity-born tamarin monkeys (Saguinus fuscicollis) were each exposed to 150 cercariae of Schistosoma mansoni (KEB strain): 6 by the percutaneous (pc) and 6 by the subcutaneous (sc) route. The prepatent period, as determined by eggs in the feces, was 34-39 days for both groups. Weekly quantitative fecal examinations revealed that although both groups actively passed eggs for as long as the duration of the experiment (18 months), the sc group excreted a significantly higher number of eggs/gram/day in the feces than did the pc group. Eggs recovered from the feces of both groups were viable: they hatched and the miracidia invaded snails which subsequently yielded infective cercariae. A significantly greater number of worms was recovered from tamarins infected by the sc route as compared to those with pc infections, and large numbers of eggs were found in affected organs of the sc group. Chronically infected tamarins with high tissue egg loads developed focal granulomatous nodules along the serosal walls of the small intestines, which in some cases, apparently had budded off to lie free in the abdominal cavity. Hepatic granulomas from animals with acute infections were significantly larger than those from chronically infected monkeys. Our results strongly suggest the presence of a skin barrier to infection in the tamarin monkey, and that if this barrier is bypassed, the tamarin can serve as a permissive host for S. mansoni. The small body size of this monkey (less than 400 g) is an obvious reason for the establishment of the tamarin monkey as a laboratory nonhuman primate model for human schistosomiasis mansoni. PMID- 3085526 TI - Effects of protective immune serum on the yields of parasites and pulmonary cell reactions in schistosome-infected rats. AB - Yields of parasites during the period of worm migration from the lungs to the portal circulation were measured in S. mansoni-infected Fischer rats passively immunized with protective serum from twice-infected donor rats. Two effects of protective serum were observed in recipient rats relative to normal serum recipients: yields of schistosomula from lungs were higher and yields of (immature) worms from the portal circulation were lower throughout the period analyzed. Histopathological analysis of lung tissue confirmed the presence of greater numbers of schistosomula in lungs of passively immunized rats. In addition, the percent of lung schistosomula involved in all categories of inflammatory reactions was greater in recipients of protective rat serum. The kinetics of accumulation of worms perfused from the portal circulation of normal and passively immunized rats indicate that in the latter group a smaller fraction of worms successfully migrates to the portal circulation. These findings support the hypothesis that protective activity of the serum prevents a portion of worms from successfully completing migration from the lung to the portal circulation. PMID- 3085527 TI - Cerebral atrophy: a schistosomiasis manifestation? AB - Preliminary studies with sonography indicated that a reduced brain mantle index and dilated ventricles were frequently seen in patients with chronic Schistosoma mansoni infection. Computerized tomography (CT) was used to confirm our earlier observations and to obtain more accurate measures. Brain scans of 25 patients with chronic S. mansoni infection showed mild to moderate degrees of cortical atrophy in 9 cases (36%) and central atrophy in 3 (12%). The remaining 16 subjects and 10 controls showed normal brain scans. The present study is the first report documented by CT showing a significant correlation between chronic S. mansoni infection and cerebral atrophy. PMID- 3085528 TI - Surgical management of life-threatening and disfiguring sequelae of fulminant meningococcemia. AB - In recent years, because of prompt diagnosis and effective, aggressive resuscitation, the majority of infants and children with fulminant meningococcemia are surviving. From 1974 through 1984, 135 patients with this diagnosis were treated, and 126 of them survived. Although a purpuric skin rash developed in almost all of these patients initially, in eight of them it progressed to multiple confluent areas of cutaneous gangrene, usually associated with extensive necrosis of underlying subcutaneous fat, fascia, skeletal muscle, and even bone. Tissue necrosis seemed to be most extensive in regions of reduced blood flow, such as the extremities, but it almost never followed a pattern of anatomic vascular distribution. A most significant microscopic finding was the presence of multiple fibrin thrombi in vessels, often in close proximity with the foci of tissue necrosis. Five children who ranged in age from 6 months to 12 years required operation. Initially, all surface wounds were treated like full thickness burns with silver sulfadiazene (Silvadene) dressings. Once the patient's condition had stabilized and the extent of tissue necrosis was apparent, all necrotic tissue was excised and the resulting wounds were temporarily covered with biologic dressings to assure a clean, viable base for skin grafting. Because the resulting quality of life postoperatively in all five surviving patients has been satisfactory, we recommend an aggressive surgical approach in patients with fulminating meningococcemia, despite what may initially appear to be devastating and even lethal complications of this disease. PMID- 3085529 TI - Combined preoperative neoadjuvant radiotherapy and chemotherapy for anal and rectal cancer. AB - Neoadjuvant therapy combining 5-fluorouracil, mitomycin C, and moderate-dose radiotherapy was given preoperatively to 29 patients with adenocarcinoma of the rectum, 3 patients with squamous cell cancer, and 1 patient with basaloid carcinoma of the anus. Significant downstaging, and even eradication, of these lesions was realized in a high percentage of cases. Population-based data for the period of 1979 to 1984 which encompasses the time of our study indicate the survival of those treated by the neoadjuvant therapy was superior to that of patients treated by surgery alone or by surgery followed by radiotherapy. In general, patients with the poorest clinical presentation had been referred for this therapy. PMID- 3085530 TI - Sodium valproate monotherapy in childhood epilepsy. AB - 154 patients with a mean age of 6 years 1 month were followed on valproate monotherapy for a period ranging from 5 to 27 months (mean 22 months). Absence epilepsies, benign myoclonic epilepsies and epilepsies with tonic-clonic seizures on awakening were the best controlled, followed by benign partial epilepsies and infantile spasms. Reduction to monotherapy resulted in improvement in 13 of 14 patients with primary generalized epilepsy. Sixteen per cent of the 154 patients suffered mild to moderate adverse effects. After cessation of treatment in 28 seizure-free patients, no recurrence was observed in absence epilepsy, benign myoclonic epilepsy, infantile spasms or benign partial epilepsy, whereas two thirds of the patients with generalized tonic-clonic seizures on awakening relapsed in the year following the cessation of the treatment. PMID- 3085531 TI - Occurrence of Aspergillus umbrosus antibodies in Danish farmers. AB - Antibodies to Aspergillus umbrosus were investigated in 181 Danish farmers, 137 farmers' spouses and a control group of 104 male blood donors with no relation to farming. By enzyme-linked immunosorbent assay (ELISA) higher levels of IgG antibodies were found in farmers than in their spouses and in non-farming controls (P less than 0.0001). By double immunodiffusion precipitating antibodies occurred in 11 farmers, in none of farmers' spouses and in one control subject. Farmers and farmers' spouses who were non-smokers had higher IgG antibody levels than smokers in the same groups (P less than 0.04). Farmers more than 30 years of age had higher IgG antibody levels than younger farmers (P less than 0.04). Farmers rearing cattle tended to have higher IgG antibody levels than farmers without cattle. No correlation between antibody levels and respiratory symptoms or lung function parameters (FEV1 or FVC) could be demonstrated. PMID- 3085532 TI - Intravenous feeding with medium chain triglycerides. Effect on blood gases and the complement system in critically ill patients. AB - Critically ill patients are usually in a catabolic state and may require total parenteral nutrition; this often includes lipid emulsions. Any adverse effects of constituents on pulmonary function, white cell function or the haemocoagulation system could have disastrous consequences in such patients. We have investigated the effects of a new intravenous lipid preparation containing medium chain triglycerides, which, in severely ill malnourished patients are theoretically a preferable energy source to conventional drug chain triglycerides. In a pilot study 17 critically ill patients whose lungs were artificially ventilated were given this lipid emulsion; no adverse effects were observed. Arterial oxygen and carbon dioxide tensions, ratio of inspired oxygen fractional concentration to arterial oxygen tension, platelet and white cell counts all remained constant and the complement system was not activated. PMID- 3085533 TI - A spectrophotometric solid-phase fibrin-tissue plasminogen activator activity assay (SOFIA-tPA) for high-fibrin-affinity tissue plasminogen activators. AB - A new spectrophotometric solid-phase fibrin-tissue plasminogen activator activity assay (SOFIA-tPA), specific for the quantitation of tissue plasminogen activators, is described. The method is based on (1) the high-affinity binding (Kp = 1.4 +/- 2 nM) of tPA to a solid-phase fibrin network constructed by thrombin proteolysis of fibrinogen covalently coupled to polyglutaraldehyde activated polyvinyl chloride microtiter plates, and (2) the subsequent development of PA activity by the fibrin-tPA complex and its measurement with a coupled assay using a chromogenic substrate highly selective for plasmin. Conditions were chosen such that the rate of para-nitroaniline release from the substrate is directly proportional to the concentration of tPA. The support is able to isolate tPA from the bulk of proteins present in any biological fluid allowing the assay to specifically detect tPA activity (range: 0.01 to 50 IU/ml) even in the presence of other activators, proteases, and inhibitors. Since the assay is done in a well-defined reaction mixture (the fibrin-tPA complex, plasminogen, and the synthetic substrate), kinetics studies using pure or crude tPA can be performed. Standard curves (rate measurement and endpoint methods) were made using the international standard (preparation 83/517) for tPA. PMID- 3085534 TI - Separation and purification of individual neurofilament proteins by reverse-phase high-performance liquid chromatography. AB - A reverse-phase HPLC method was developed to separate individual neurofilament proteins (210,000, 160,000 and 70,000 Da) from the glial fibrillary acid protein. It is useful for analytical or preparative methods, with yields higher than 80%. The method represents improvement over previous methods in speed, efficiency, and purity. Combining this HPLC method with the conventional chromatographic method on DEAE-cellulose, highly purified individual neurofilament proteins can be obtained in large scale. PMID- 3085535 TI - Quantification of chymosin action on nonlabeled kappa-casein-related peptide substrates by ultraviolet spectrophotometry: description of kinetics by the analysis of progress curves. AB - A method is described for quantifying the proteolytic action of the milk-clotting enzyme chymosin on small and medium-sized peptide substrates by monitoring the decrease of absorbance at 230 nm during cleavage. The method is illustrated by the determination of the kinetic parameters of the specific splitting of a kappa casein-related hexa- and pentadecapeptide by chymosin. The results are in good agreement with those found earlier with the same enzyme/substrate system by using an automated ninhydrin method. Erroneous results were obtained when the kinetic data were derived from one single progress curve. The significance of initial rate measurements for calculating correct kinetic parameters is briefly discussed. The usefulness of single progress curves measured at different initial substrate concentrations for obtaining information about the mechanism of the enzymic reaction is demonstrated. PMID- 3085536 TI - Coomassie brilliant blue G-250 dye-binding technique for determination of autolytic protein breakdown in Euglena gracilis and comparison to other methods of autolysis measurement. AB - The Coomassie brilliant blue G-250 dye-binding technique of M. M. Bradford (1976, Anal. Biochem. 72, 248-254) for protein quantification has been used to measure autolytic protein breakdown in cell-free extracts of Euglena gracilis. Specific autolysis rates were calculated from the difference between initial and actual absorbances at different incubation times of Coomassie brilliant blue-stained protein. They were found to depend linearly on time and initial protein concentration. Calibration against another method of protein determination is necessary due to different color yields with various protein mixtures. The high sensitivity and reproducibility of this method permit determination of specific autolysis rates below 0.1% mg-1 h-1 over a pH range between 3 and 8, without protein precipitation or pH adjustment, and in the presence of high amounts of amino acids and/or small peptides. Results obtained by this method are comparable to those of other autolysis measurements and to proteolytic activity determination by azocaseinolysis. Proteolytic autolysis has been observed in both the soluble and the particulate fractions of E. gracilis cell-free extracts, but displays different pH optima and specific activities in these fractions, as is also the case for azocaseinolysis. The method described is easy to perform, inexpensive, time saving, and should be applicable to other biological systems as well. PMID- 3085537 TI - A fluorogenic, mixed-disulfide reagent for thiol assay. AB - The design and synthesis of the mixed disulfide (ortho-nitroaniline-N ethyldithio) 2-[pyridyl-5-thioureido-N'-(5-fluorescein)] are described and the chemical and spectroscopic properties of this thiol-specific fluorogenic reagent are presented. The high reactivity and sensitivity of this reagent in thiol assay are demonstrated with low-molecular-weight thiols and with human carbonmonoxyhemoglobin and its subunits. Comparison with conventional absorption methods shows that at least 100 times less material is needed; moreover, high background absorbance or turbidity do not interfere with the assay. PMID- 3085538 TI - [14C]acrylonitrile: preparation via a stable tosylate intermediate and quantitative reaction with amine residues in collagen. AB - A simple, convenient synthetic procedure for [14C]acrylonitrile is described. Na14CN is used as the radioactive starting material. Small (milligram) amounts are converted to 3-[14C]Hydroxypropionitrile by a substitution reaction with 2 chloroethanol. 3-[14C]Hydroxypropionitrile is then tosylated, and the specific activity of this intermediate product is easily determined using its uv extinction coefficient and scintillation counting. [14C]Acrylonitrile is obtained rapidly on distillation by heating the tosylate in the presence of a high boiling tertiary amine base catalyst. The tosylate intermediate can be stored, in contrast to radioactive acrylonitrile, which is unstable. The reaction of acrylonitrile with lysine, hydroxylysine, and histidine residues in human Achilles tendon collagen, as well as chromatographic separation and identification of the carboxyethyl derivatives of these amino acids, is also described. PMID- 3085539 TI - A fast, nondestructive purification scheme for prostaglandin H2 using a nonaqueous, bonded-phase high-performance liquid chromatography system. AB - Arachidonic acid metabolism produces several biologically important compounds including the leukotrienes and prostaglandins. Prostaglandin H2 (PGH2) is the first metabolite in the arachidonic acid cascade leading to all other prostaglandins. Pivotal to our understanding of PGH2's biology is the ability to separate it in pure form from the numerous other arachidonic acid metabolites produced in a biological milieu. The extensive literature on PGH2 biology and metabolism has relied almost exclusively on the traditional method of separation using gravity flow silicic acid columns. In our hands, such PGH2 preparations were found to contain varying amounts of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), PGE2, PGF2 alpha and other minor impurities as determined by further chromatographic and mass spectral analyses. Analytical separation of PGH2 and other arachidonic acid metabolites has been accomplished using reversed-phase HPLC. However, the labile nature of this molecule in aqueous systems makes such techniques unacceptable for preparative isolation of high purity PGH2 and has necessitated the development of a totally nonaqueous separation. To this end, we attempted several stationary phases and found that the cyano-bonded phase showed the best selectivity for resolving PGH2 from its major contaminants. Separations were performed on self-packed columns using a hexane-isopropanol gradient. Peaks were detected both by liquid scintillation counting and uv spectrophotometry (214 nm). Structure assignments were made by chromatographic comparison with authentic standards (PGF2 alpha, PGE2), biological activity (PGH2--platelet aggregation), and by ammonia direct chemical ionization mass spectrometry (HHT, hydroxy 5,8,10,14-eicosatetraenoic acid, PGH2, PGE2, PGF2 alpha). The latter technique, which by its very nature volatilizes all organic material in the sample, was particularly useful in determining not only that the PGH2 preparations were free from the aforementioned side products, but that they were also free from lipid, protein, and other potential residues frequently found in biological preparations. PMID- 3085540 TI - Applications of chemical cleavage procedures to the peptide mapping of neurofilament triplet protein bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AB - A procedure for examining possible sequence homology in the triplet neurofilament proteins using a sodium dodecyl sulfate-polyacrylamide gel electrophoresis system is described. Five different chemical reagents (cyanogen bromide, BNPS-skatole, hydroxylamine, formic acid, and nitrothiocyanobenzoic acid) have been used for peptide mapping studies. Potential applications of this technique are discussed. PMID- 3085541 TI - Isolation of phosphoproteins by immobilized metal (Fe3+) affinity chromatography. AB - Phosphoproteins and phosphoamino acids bind to ferric ions immobilized on iminodiacetate-agarose gel and can be eluted by increasing pH or by introducing phosphate ions to the eluant. Some other metals were found to resemble iron with regard to the interaction with protein-bound phosphate and phosphoamino acids. These observations were utilized to develop purification procedures for phosphoproteins. Hen egg albumin (ovalbumin) was fractionated into three components of varying phosphate contents. Porcine pepsin was purified in a similar manner. PMID- 3085542 TI - Isolation of a physiologically active and a physiologically inactive mitochondrial NADH-ubiquinone reductase (complex I) from donkey hearts. AB - The method described for the isolation of mitochondrial complex I (NADH ubiquinone reductase) from bovine hearts could not be applied to donkey hearts as unacceptably large losses in enzyme activity occurred. This method was modified for the isolation of complex I using donkey hearts and two complexes were obtained: complex IA which was physiologically inactive and complex IB which was physiologically active as it catalyzed the reaction from NADH to ubiquinone. Both complexes had relatively low enzyme activity with artificial electron acceptors, except with potassium ferricyanide, and had more or less the same amount of acid labile sulfur and nonheme iron although the polypeptide composition differed to a great extent. PMID- 3085543 TI - A fluorometric assay for biotinidase. AB - An assay for biotinidase using biocytin, the natural substrate, is described. The fluorometric procedure uses 1,2-diacetylbenzene which reacts selectively with lysine allowing its direct determination in mixture with biocytin. We have examined the applicability of the assay using human serum biotinidase. PMID- 3085544 TI - Quantification of apolipoproteins in rat serum and in cultured rat hepatocytes by enzyme-linked immunosorbent assay. AB - An enzyme-linked immunosorbent assay (ELISA) has been developed to measure apolipoproteins in rat serum. Nondelipidated whole serum was heat-treated at 52 degrees C for 3 h in phosphate-buffered saline containing 0.1% Tween-20 before assay. Monospecific rabbit anti-rat apolipoprotein antibodies were added to 96 well polystyrene microtiter plates which had been coated with purified rat serum apolipoproteins or unknown samples. After incubation and washing, goat anti rabbit serum antibodies conjugated with horseradish peroxidase were added to the plates and incubated. The bound peroxidase activity was assayed after further washing. Serum apolipoprotein concentrations were calculated by comparison against purified standards that were assayed simultaneously with the unknown samples. The intraassay coefficients of variation for apolipoprotein AI, E, and AIV (Apo AI, E, and AIV) were 2.3, 4.4, and 5.3%, and interassay coefficients of variation were 6.1, 5.5, and 7.9%, respectively. The ELISA assay is sensitive to nanogram quantities of rat serum apolipoproteins and the results agree well with those measured by densitometry. The serum concentrations of Apo AI, E, and AIV of a normal fed rat were found to be 504 +/- 8, 413 +/- 20, and 262 +/- 20 micrograms/ml, respectively. When cultured as monolayers in Waymouth's medium for 1 day, rat hepatocytes secreted Apo AI, E, and AIV at rates of 2.51, 61.8, and 48.9 ng protein/mg cell protein/h. PMID- 3085545 TI - Separation of chloroplast polar lipids and measurement of galactolipid metabolism by high-performance liquid chromatography. AB - Procedures are described for the separation of polar lipids from plant chloroplasts by high-performance liquid chromatography, using a polar-modified silica column. Glycolipids and phospholipids were eluted with a gradient of 2 propanol/n-hexane (80:55, v/v) and 2-propanol/n-hexane/water/methanol (80:55:15:10, v/v). The lipids were detected by uv absorbance at 202 nm. Diacylglycerol and mono-, di-, and trigalactosyldiacylglycerol and phosphatidylcholine were separated on a LiChrosorb NH2 column (7-microns particles, Merck, FRG), but acidic lipids were retained. These lipids could be quantified from their 202-nm absorbance recording. The absorption coefficients obtained depended on the mean number of double bonds in the different lipid classes. The separation was applied for a rapid monitoring of the lipid composition in thylakoids and in fractionated inner and outer envelopes. The activities of galactosyltransferases involved in galactolipid metabolism, UDPGal:diacylglycerol galactosyltransferase and galactolipid:galactolipid galactosyltransferase, could be measured quantitatively in specific assays for both enzymes. PMID- 3085546 TI - Development and analytical performance of tubular polymer membrane electrode based carbon dioxide catheters. PMID- 3085547 TI - [Cloverleaf skull deformity with thanatophoric dysplasia in the 24th week of pregnancy]. AB - A case of cloverleaf skull anomaly with thanatophoric dysplasia could be examined pathologico-anatomically in the age of 24 weeks of gestation. There were typical radiological and morphological signs of a mild form of thanatophoric dysplasia. Additionally a cloverleaf skull anomaly with premature fusion of sutures and a disturbed ossification without any signs of haemangiomatosis of the desmocranium was found. A hydrocephalus was not demonstrable. PMID- 3085548 TI - Orthogonal arrays of particles in the gastric parietal cell of the rat: differences between superficial and basal cells in the gland and after pentagastrin or metiamide treatment. AB - The basolateral plasma membrane of gastric parietal cells is characterized by the presence of orthogonal arrays of particles revealed by the freeze-fracture technique. These arrays were quantitatively assessed in freeze-fracture replicas of the gastric mucosa at two different levels of the gastric gland and after pentagastrin and metiamide treatment. The arrays were small and scarce in parietal cells located in the upper part of the gland, while they were markedly more abundant in parietal cells situated at the base of the gland. In both superficial and basal cells, the concentration of the arrays was significantly decreased after pentagastrin or metiamide treatment. This decrease was not due to an increase in the surface area of the basal plasma membrane. These results indicate that the concentration of the orthogonal arrays is a distinctive feature between superficial and basal parietal cells and that the arrays can be modulated by parietal cell function. PMID- 3085549 TI - Increased norepinephrine release from dog pulmonary artery caused by nitrous oxide. AB - The effects of nitrous oxide on the release and metabolism of norepinephrine (NE) at neuroeffector junctions in dog pulmonary artery were examined. Helical strips of artery were incubated in Krebs-Ringer solution containing L-(3H)NE and mounted for superfusion. The arterial strips were studied in the presence of 95% oxygen 5% carbon dioxide, 70% nitrogen-30% oxygen, or 70% nitrous oxide-30% oxygen. During the 60 min of each experiment, five samples of superfusion fluid were collected for analysis and the effluxes of (3H)NE and its radiolabeled metabolites were measured before and during electrical stimulation and during recovery from stimulation. (3H)Norepinephrine was separated from its metabolites in the superfusate and in extracts of artery by column chromatography and quantitated by liquid scintillation spectrometry. Nitrous oxide significantly increased the fractional loss of total radioactivity and the amount of NE in the superfusate both during resting conditions and during stimulation. Nitrous oxide had no effect on the proportions of radioactivity among metabolites of NE in the superfusate or on the profile of NE metabolites remaining in the tissue after experimentation. These findings are consistent with increased NE release as a direct effect of nitrous oxide on nerve endings. PMID- 3085550 TI - Response of left ventricular ejection fraction to recovery from general anesthesia: measurement by gated radionuclide angiography. AB - To test the hypothesis that, after anesthesia for noncardiac surgical procedures, the increased cardiac work during recovery induces wall motion and ejection fraction (EF) abnormalities in patients with mild angina pectoris, gated radionuclide angiography was performed in patients undergoing simple cholecystectomy under narcotic-relaxant general anesthesia. The ejection fraction was determined during anesthesia at the end of surgery, and then determined 3 min and 3 hr after extubation. A new angiography was performed 24 hr later, and a myocardial scintigraphy (Thallium 201) was performed during infusion of the coronary vasodilator, dipyridamole. In the first part of the investigation, eight patients without coronary artery disease (CAD) (group 1) and 20 patients with mild angina (group 2) were studied. In the second part of the study, seven patients (group 3) with mild angina pectoris received an intravenous infusion of 0.4 microgram X kg-1 X min-1 of nitroglycerin started before surgery and gradually decreased 4 hr after extubation. In group 1, EF remained unchanged at recovery. In contrast in group 2, EF responded abnormally to recovery: EF decreased from 55% during anesthesia to 45% 3 min after extubation (P less than 0.001). Patients in group 3, who received intravenous nitroglycerin, showed no change of EF at recovery. This study demonstrates that recovery from general anesthesia causes abnormalities in left ventricular function in patients suffering from CAD. These abnormalities are prevented by prophylactic intravenous nitroglycerin. PMID- 3085552 TI - Roles of fentanyl and nitroglycerin in prevention of myocardial ischemia associated with laryngoscopy and tracheal intubation in patients undergoing operations of short duration. AB - The purpose of this study was to evaluate intravenous nitroglycerin given during induction of anesthesia as a means for prevention of myocardial ischemia and hemodynamic changes associated with induction, laryngoscopy, and intubation, in patients with stable angina scheduled for vascular operations of moderate duration. Forty-six patients were randomly assigned to receive either fentanyl, 3 micrograms/kg (group 1, n = 6), fentanyl, 8 micrograms/kg (group 2, n = 20), or fentanyl 3 micrograms/kg plus a continuous intravenous nitroglycerin infusion, 0.9 microgram X kg-1 X min-1 (group 3, n = 20), in addition to thiopental pancuronium anesthetic induction, prior to laryngoscopy and intubation. The criteria for recognizing myocardial ischemia were the following: horizontal or downsloping ST segment depression equal to or greater than 1 mV, and/or ventricular arrhythmia, on CM5 recording. In group 1, myocardial ischemia occurred during laryngoscopy and intubation in four patients, and mean blood pressure (MBP), heart rate, and mean pulmonary wedge pressure (PCWP) increased significantly (P less than 0.05). Despite greater stability in MBP and heart rate in group 2, myocardial ischemia still occurred in four patients (not significantly different from group 1). Nitroglycerin added to low-dose fentanyl (group 3) produced significant reduction in myocardial ischemia (1/20) when compared with group 1 (P less than 0.01), and significantly greater stability in PCWP during laryngoscopy and intubation in comparison to groups 1 and 2. In patients with stable angina undergoing operations of short duration, the use of nitroglycerin infusion and low-dose fentanyl significantly decreases the incidence of myocardial ischemia associated with induction of anesthesia and tracheal intubation. PMID- 3085551 TI - Failure of nalbuphine to antagonize morphine: a double-blind comparison with naloxone. AB - The authors studied the respiratory and analgesic effects of nalbuphine (0.21 mg/kg, intravenous), naloxone (0.014 mg/kg, intravenous), and placebo (normal saline) when given after morphine (0.21 mg/kg, intravenous) in a double-blind, randomized fashion. Resting end-tidal CO2 (PETCO2), ventilatory and occlusion pressure responses to CO2 rebreathing, and pain threshold were measured in 12 healthy adult volunteers before, 5 min, and 30 min after morphine. Nalbuphine, naloxone, or saline were administered 55 min after morphine, and the above measurements were repeated 5 min later (60 min after morphine) as well as 90, 120, 180, and 240 min after morphine. Whereas naloxone reversed respiratory depression as measured by all three respiratory parameters, nalbuphine either further depressed (resting PETCO2) or did not affect (ventilatory and occlusion pressure responses to CO2 rebreathing) respiratory drive. Morphine produced a significant elevation of the pain threshold. Significant decreases in the pain threshold were seen only after naloxone. Saline and nalbuphine did not significantly alter the pain threshold. The data indicate that nalbuphine may not reliably antagonize moderate doses of morphine. PMID- 3085553 TI - Gas exchange during controlled ventilation in children with normal and abnormal pulmonary circulation: a study using the single breath test for carbon dioxide. AB - Carbon dioxide single breath tests (SBT-CO2) were obtained during anesthesia and controlled ventilation in 42 children about to undergo thoracic surgery. The tests were obtained with a computerized system based on the Servo ventilator. The system made on-line corrections for compressed volume, apparatus deadspace, and rebreathing. Children with normal pulmonary circulation had excellent gas exchange with high PaO2 values, a mean alveolar deadspace fraction (VDalv/VTalv) of 0.10, and a gently sloping phase III of SBT-CO2. Children with pulmonary hyperperfusion (left to right shunting) due to an atrial septal defect or a ventrical septal defect had significantly lower PaO2 values, steeper phase III slopes, and a greater spread of values for VDalv/VTalv. Children with pulmonary hypoperfusion due to pulmonary stenosis in combination with intracardiac right to left shunting had extremely low PaO2 values, and "adult" values for VDalv/VTalv. They required increased ventilation to maintain CO2 homeostasis. In the pooled material, the airway deadspace was strongly correlated to height, weight, and age. The airway deadspace was unaffected when tidal volume was increased by 37%, and ventilatory frequency simultaneously reduced by 30%, a maneuver that left alveolar ventilation unchanged. This is probably because an end-inspiratory pause was used; when frequency is reduced the length of the end-inspiratory pause increases, allowing proximal diffusion of the alveolar/fresh gas interface. PMID- 3085555 TI - Papers to be presented at APIC '86 (Association for Practitioners in Infection Control): Thirteenth annual educational conference. May 4-9, 1986, Las Vegas, Nevada. Abstracts. PMID- 3085554 TI - Partial preservation of cerebral vascular responsiveness to hypocapnia during isoflurane-induced hypotension in dogs. AB - This study was undertaken to determine whether the cerebral vascular response to hypocapnia is preserved during isoflurane-induced hypotension. In six dogs (group 1) cerebral vascular resistance and cerebral blood flow were determined at normocapnia (PaCO2 40 mm Hg) and at hypocapnia (PaCO2 20 mm Hg) while mean arterial pressure was normal, and then again during isoflurane-induced hypotension to a mean arterial pressure of 50 mm Hg. Hypocapnia increased cerebral vascular resistance and decreased cerebral blood flow during both normotension and isoflurane-induced hypotension. However, the magnitude of these responses was greater when mean arterial pressure was normal. In another six dogs (group 2), CO2 responsiveness was examined during isoflurane-induced hypotension without prior determination of CO2 responsiveness at normal mean arterial pressure and during sodium nitroprusside-induced hypotension to a mean arterial pressure of 50 mm Hg. As in group 1, partial preservation of CO2 responsiveness was observed during isoflurane-induced hypotension; the magnitude of the response in group 2 during isoflurane-induced hypotension was similar to that in group 1. In contrast, in group 2 during sodium nitroprusside-induced hypotension, hypocapnia caused no significant change of cerebral vascular resistance or cerebral blood flow. It is concluded that cerebral vessels respond to changes in PaCO2 differently during isoflurane-induced hypotension than during hypotension with other commonly used hypotensive treatments. Hypocapnia decreases cerebral blood flow during isoflurane-induced hypotension and, therefore, may also decrease cerebral blood volume, brain bulk, and intracranial pressure. PMID- 3085556 TI - [In vitro bactericidal activity of polyvinylpyrrolidone iodine on Neisseria gonorrhoeae]. AB - A standardized methodology was used to study the in vitro behavior of different strains of Neisseria gonorrhoeae when treated with povidone-iodine. The bactericidal activity of the antiseptic was appraised using the dilution neutralization technique on four gonococcal strains, two of which produced a beta lactamase. Bactericidal activity in aqueous medium was observed down to a dilution of 1/128. This result specifies the conditions under which this antiseptic is active against Neisseria gonorrhoeae. PMID- 3085557 TI - [Successes and failures of the activated partial thromboplastin time in the preoperative evaluation]. AB - In a prospective study assessing haemostatic functions, the activated partial thromboplastin time was prolonged in 134 out of 10,229 patients studied, without an increase in the prothrombin or thrombin times; this abnormality persisted in only 37 of them on a new blood sample. A retrospective analysis was made of 265 patients who had such an isolated prolongation of the activated partial thromboplastin time on two successive blood samples: the causal abnormality remained unexplained in 135 patients; a well defined coagulation disorder without abnormal bleeding tendency was present in 110 patients (1 severe factor XII deficiency, 58 partial factor XI or XII deficiencies and 51 lupus anticoagulants); a bleeding disorder was diagnosed in 20 patients (8 haemophilias, 8 Von Willebrand's diseases, 4 factor VIII inhibitors). The well iron efficacy of the activated partial thromboplastin time for detecting coagulation abnormalities is counter-balanced by some disadvantages such as the delay for biologic conclusions. In the preoperative assessment of haemostatic functions, rather than taking a routine approach, it would seem better to determine for each patient the need and the extent of biological testing according to the type of planned surgery, the clinical status of the patient and possible bleeding symptoms. PMID- 3085558 TI - [Artificial nutrition in hospitals: general principles of quality control]. AB - Sterile pharmaceutical preparations must be supplied to clinical wards; their high degree of safety is given by hospital pharmacists who are responsible for quality control of these preparations. Various considerations on the choice of protocol are suggested. Good manufacturing practice is to carry out quality controls at every stage of production of total parenteral nutrition fluids. However, these controls are made difficult by the poor equipment of hospital pharmacies and by the absence of specific pharmaceutical monographs. The selected protocol involves: preliminary controls, which determine the practicability of the suggested formulation, as well as its expiration date: amino acid determinations using liquid chromatography, electrolyte analysis and concentration, pH, evolution of particle size in fat emulsion according to storage conditions, choice of plastic container; microbiological controls: every two months and every time the pharmaceutical staff changes; moreover, a search for bacterial endotoxins using a chromogenic substrate (LAL technique) with "microstrips" is suggested; a sample from each admixture is kept under refrigeration for 15 days; controls during fabrication to check, at the end of the process, if good manufacturing practices have been realized: microbiological sampling of the working area and elaboration of a written procedure; control after fabrication of each nutrient admixture: determination of various elements such as sodium, potassium and dextrose in a 5 ml sample. These assays enable the checking of high standards of fabrication. Hospital pharmacies, despite their reduced equipment, can answer by these procedures to the physicians' needs and supply sterile TPN meeting pharmaceutical standards. PMID- 3085559 TI - Effect of nifedipine on cerebral high-energy phosphates after cardiac arrest and resuscitation in the rat. AB - We studied the effect of nifedipine, a calcium entry blocker, on the recovery of cerebral adenosine triphosphate (ATP), creatine phosphate (CP), and lactate levels following resuscitation from cardiac arrest. Using the cardiac arrest and resuscitation model of de Garavilla, Babbs, and Tacker with an arrest time of eight minutes, 76% of the animals arrested were resuscitated with an average intermittent abdominal compression-CPR time of 3.3 minutes. Rats were assigned randomly to the following groups: nonischemic; eight minutes of arrest without resuscitation; and postresuscitation treatment with either IV normal saline; 3 micrograms/kg nifedipine; 10 micrograms/kg nifedipine; or 30 micrograms/kg nifedipine. Treated animals were sacrificed at either 20 or 120 minutes thereafter. As expected, after eight minutes of cardiac arrest, the levels of ATP and CP dropped to near 0 and rebounded in all resuscitated animals. By 120 minutes after resuscitation, rats given the 10-micrograms/kg dose of nifedipine had levels of ATP equivalent to nonischemic values. Return of CP values to nonischemic levels was seen only at the 3-micrograms/kg dose and was independent of time of measurement. The ATP and CP levels in these nifedipine-treated groups were significantly better when compared to saline-treated controls. There were no treatment-dependent differences in lactate levels. We conclude that clinically appropriate doses of nifedipine had a beneficial effect on the recovery of cerebral high-energy phosphates after cardiac arrest and resuscitation. PMID- 3085560 TI - Ventricular arrhythmias during treatment for acute asthma. AB - A double-blind, randomized study was performed to determine the occurrence of ventricular arrhythmias in acute asthma patients treated with epinephrine, aminophylline, or both in combination. Sixty patients were studied with Holter monitoring during the 90-minute study period. There was no statistical difference among the study groups in frequency or grade of ventricular arrhythmia. Combination treatment of acute asthma with these drugs is as safe as treatment with either alone. PMID- 3085562 TI - Bilateral shoulder dislocations. PMID- 3085561 TI - Lead toxicity masquerading as sickle cell crisis. AB - We recently saw a 12-year-old black boy with known sickle cell disease who had been seen many times for abdominal pain thought to be secondary to a vasoocclusive crisis. The patient eventually was admitted, after a seizure and the onset of obtundation. The etiology of his acute encephalopathy remained unclear until bone films of his knees fortuitously revealed "lead lines." The patient was treated and did well subsequently. This case emphasizes the importance of considering other diagnoses when a sickle cell patient presents with a crisis. PMID- 3085563 TI - The platelet thromboxane inhibitor, dazmegrel, does not reduce monocrotaline induced pulmonary hypertension. AB - Monocrotaline injures rat pulmonary endothelium, and pulmonary vascular remodeling, pulmonary hypertension, and right ventricular hypertrophy then develop. Platelets contribute to development of the pulmonary hypertension because platelet depletion 1 wk after monocrotaline administration reduces the right ventricular hypertrophy. To determine whether the platelet action is through thromboxane A2 generation, we administered the long-acting thromboxane synthetase inhibitor dazmegrel (UK-38,485) to rats receiving monocrotaline. Both before and after monocrotaline treatment, dazmegrel effectively (p = 0.01) reduced thromboxane release during clotting, platelets being the main source. We then studied 4 groups of rats: 1 group of rats received only monocrotaline as a single subcutaneous injection at 0 h; a second group received, in addition, dazmegrel in drinking water starting at -48 h, then daily until Day 21; a third group received only dazmegrel; a control group received no treatment. Dazmegrel did not prevent monocrotaline-induced growth retardation. Despite adequate intake and coverage of the critical period at approximately 1 wk after monocrotaline treatment, dazmegrel did not significantly prevent the development by Day 21 of right ventricular hypertrophy. On Day 21, platelet counts and plasma thromboxane B2 levels were similar in all 4 groups, suggesting no major platelet involvement at that time. It seems that the platelet contribution to pulmonary hypertension after monocrotaline treatment is not mediated by thromboxane A2. PMID- 3085565 TI - Congenital gastric anomalies. AB - A review with a classification of congenital defects involving the stomach is presented. Owing to the fact that in certain lesions there are so few case reports available for study, the etiology and true nature of these defects remains unknown. It is incumbent upon the surgical community to continue to document congenital anomalies of the stomach and report them accordingly. PMID- 3085564 TI - Endotoxin and lung injury. AB - Two things are certain: endotoxin has dramatic effects on the structure and function of the lungs in intact animals and also on isolated lung cells, and both the in vivo and in vitro effects of endotoxin are complex. In whole animals, endotoxin causes obvious and subtle effects on functions of both airways and the pulmonary circulation. These effects include diffuse lung inflammation and injury of pulmonary vascular endothelium. Endotoxin can also directly injure endothelial cells in vitro. In vivo, lung injury caused by endotoxin is at least partly dependent on the presence of granulocytes, and some evidence also suggests that both lymphocytes and macrophages may participate in the response either directly or by directing cell traffic. At least in the sheep preparation, platelets do not seem to play a major role in the lungs' response to endotoxemia. Although endotoxin can activate complement and activated complement infused into whole animals affects the lungs, it seems unlikely that complement activation alone is sufficient to explain the severe and prolonged lung injury caused by endotoxin. Cyclooxygenase metabolites of arachidonic acid appear to mediate both changes in lung mechanics and pulmonary vasoconstriction after endotoxemia. Lipoxygenase products may play a role in these responses as well as the inflammatory response and increases in vascular permeability, although evidence for these latter speculations is not firm. Lung cell injury caused by endotoxin probably is mediated at least in part by generation of free radicals. Inflammatory cells, especially neutrophils, are one source of these toxic oxygen species, but intracellular generation of free radicals within lung cells per se may also be stimulated by endotoxin and account for some of the lung injury. Likewise, inflammatory-cell-derived proteinases may mediate endotoxin-induced injury of lung cells and, as with chronic lung diseases, balance between proteinases and antiproteinases could be important. The fact that free radicals can inactivate antiproteinases, and antiproteinases can act as free radical scavengers, may suggest a complex relationship among the several possible mediators of toxicity. Cyclic nucleotide metabolism is affected in whole animals and isolated lung cells by endotoxin and these classic second messengers could be involved in the pathogenetic sequence, but exactly how is unclear. Chronic effects of endotoxin on the lungs may provide a pathogenetic link between acute lung injury and chronic changes in lung structure and function.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3085566 TI - Should perimenopausal women be screened for osteoporosis? AB - The increasing availability of noninvasive methods for measuring bone mass raises the issue of whether perimenopausal women should routinely have such measurements to identify those at risk for osteoporotic fractures of the hip, wrist, and spine. Although the mortality and morbidity caused by hip fractures would warrant routine screening, measurement of bone mass has uncertain value in assessing the risk for hip fracture. Wrist fractures generally cause only transient disability, and measurement of bone mass may not reliably predict risk. Measurements of bone density of the spine might be better able to assess a woman's risk for vertebral fractures, but the value of screening depends on whether the findings would affect a woman's decision about using estrogen therapy after menopause. Serial measurements of bone mass to estimate a woman's rate of bone loss are relatively imprecise, increase the cost of screening, and have at best a limited role in screening women to assess risk for osteoporotic fractures. PMID- 3085567 TI - The case of Claire Conroy: will administrative review safeguard incompetent patients? AB - The emotional issue of withdrawing feeding tubes from incompetent patients was reviewed recently by the New Jersey Supreme Court in the case of Claire Conroy. The court ruled that artificial feedings do not differ from other life-sustaining treatments and may be withdrawn or withheld if they are against the patient's wishes or best interests. The ruling rejected the tradition of shared decision making by physicians and families of incompetent patients. Instead, the court required the State Ombudsman to investigate cases like that of Claire Conroy as possible cases of elder abuse. Although such review was intended to safeguard vulnerable patients, it may have detrimental effects and impede humane decisions to withhold care. To minimize cumbersome decision-making procedures, physicians should discuss life-sustaining treatment in advance with patients who are still competent. Such discussions should be more specific than is now customary. PMID- 3085568 TI - Neuropathological consequences of chemically and electrically induced seizures. PMID- 3085569 TI - Dosage, seizure threshold, and the antidepressant efficacy of electroconvulsive therapy. PMID- 3085570 TI - Parallel organization of functionally segregated circuits linking basal ganglia and cortex. PMID- 3085571 TI - [Value of a preformed spatulate plate for the treatment of various fractures of the lateral malleolus]. PMID- 3085572 TI - [Hemodynamic effects of microencapsulated delayed-release nitroglycerin in acute myocardial infarction]. AB - The hemodynamic effects following an oral dose of 19.5 mg of nitroglycerin microencapsulated to give prolonged release have been studied in 10 patients during the 48 hours which followed the establishment of a myocardial infarct complicated by moderate left cardiac insufficiency. The right auricular pressure and the pulmonary capillary pressure diminished significantly 20 minutes after the dose; 4 hours later the persistence of these effects is significant. A transient diminution of the systolic arterial pressure was observed initially (p less than 0.05). We observed that the cardiac index tends to increase although the increase did not attain the threshold of significance. No difference was observed in cardiac frequency, diastolic and mean arterial pressure and in the systemic vascular resistance. We conclude that in the patient presenting an acute myocardial infarct, 19.5 mg of NTG, microencapsulated to give prolonged release, essentially produce a reduction of the preload, with an early onset of action and a hemodynamic efficacy lasting at least 4 hours. PMID- 3085573 TI - Cooperation of lymphokine(s) and macrophages in expression of antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). AB - The administration of IFN containing sera (Ge-sera) obtained from Ge-132-treated mice (Ge-mice) or the passive transfer of macrophages (M phi) to mice bearing ascites tumors resulted in the inhibition of tumor growth. The cooperative role of Ge-sera and Ge-M phi in the display of Ge-132-antitumor activity was studied. When mice were pretreated with antimouse IFN gamma antiserum, no IFN-inducing and antitumor activities of the compound were detected. Cytotoxic activities were detected on peritoneal M phi of mice treated with Ge-sera, and passive transfer of these M phi to tumor-bearing mice resulted in the inhibition of tumor growth. When tumor-bearing mice were pretreated with substances toxic to M phi, there was no antitumor activity of Ge-sera observed. However, there was antitumor activity of Ge-sera in mice depleted of T-cells, even though the antitumor effects of the compound itself were not demonstrable in T-cell depleted mice. Therefore, a part of the antitumor activity of Ge-132 may appear to be expressed as follows: (1) Ge 132 stimulated T-cells to produce circulating lymphokine(s) which were inactivated by anti-IFN gamma treatment; (2) activated M phi were generated from resting M phi by such lymphokine(s); (3) the transplanted tumors were inhibited by these M phi. PMID- 3085574 TI - Binding of fluorescein isothiocyanate conjugated lectins to MXT mouse mammary neoplasm and their relation to steroid receptor status. AB - As previous studies have suggested a hormone dependence of binding sites for peanut agglutinin in mammary neoplasm, this feature has been thought to be correlated to steroid receptor status. The present investigation was undertaken on a well-established ovarian-dependent cancer model in order to check this hypothesis. Sections of primitive tumor transplants as well as of tumors induced in vivo by injection of cell clones were analyzed with the use of three fluorescent lectins. The lectin binding sites were evaluated semi-quantitatively and compared with estrogen and progesterone receptor levels. Using non-parametric statistical tests, the results revealed a strong correlation between the expression of peanut agglutinin (PNA) binding sites and steroid receptor status, but only in primitive tumor transplants. No such correlation was observed in tumors induced in vivo, by injection of cell clones. No correlation between the steroid receptor status and the two other lectins (Concanavalin A and Dolichos biflorus) was observed. These data suggest that PNA can be used as a valuable histochemical tool in steroid hormone dependence study. PMID- 3085575 TI - Combined radiotherapy, chemotherapy, and maltose tetrapalmitate immunotherapy in the treatment of 4'dimethylaminoazobenzene-induced liver cancer. AB - Therapeutic effects of radiotherapy (R), chemotherapy, and maltose tetrapalmitate (MTP) immunotherapy alone and in combinations were tried against 4' dimethylaminoazobenzene (DAB) induced primary liver cancer in Wistar rats in three separate protocols. Rats were fed a low protein synthetic diet containing 0.06% DAB for 90-120 days. Around 90 days, liver cancers developed in all the animals. In the first protocol, animals were either left untreated or treated with cyclophosphamide (Cy), MTP (i.p. or oral) and Cy plus oral MTP. Rats in the MTP (i.p.) group maintained a steady liver weight but neither Cy nor Cy + MTP influenced the survival time or liver weight. In the second protocol, R as well as a 3-drug combination at 2 dose levels were tried alone and with MTP before or soon after cessation of DAB feeding. Survival times were decreased by R and chemotherapy due to combined toxicities of DAB and treatments and were partially restored by MTP. In the third protocol, MTP, R, and Cy were each tried alone and in combinations, 21 days after cessation of 100-day DAB feeding. Increase in survivals were obtained by each treatment, although tumor weight was best controlled by triple R+ Cy + MTP combination. PMID- 3085576 TI - [Drug treatment of oligospermia of idiopathic origin. Critical review]. AB - Controlled studies are essential in any evaluation of the effects of treatment in cases of sterility due to oligospermia because of the important inter-individual variations in the sperm count and in the spontaneous pregnancy rate. The various hormonal and non-hormonal treatments for idiopathic oligospermia are described with special emphasis on the results of double-blind studies. Future prospects for the treatment of male sterility by in vitro fertilisation are then discussed. PMID- 3085577 TI - Thymosin beta 4 is a shared antigen between lymphoid cells and oligodendrocytes of normal human brain. AB - In the normal human brain, immunoreactive thymosin beta 4, a well-characterized thymic extract, was demonstrated specifically in the cell bodies and processes of a subset of interfascicular and satellite oligodendrocytes with their stained processes terminating around myelin sheaths. Antisera directed against two other thymic polypeptides, thymosin alpha 1 and alpha 7, did not react. In lymphoid tissues, thymosin beta 4 was present in macrophages, Langerhans' cells of the skin, and the interdigitating cells of the thymus. Thus, a subset of oligodendrocytes shares a common antigen of thymic origin with the reticular dendritic and phagocytic lymphoid cells--all Ia+ immunocompetent cells that participate in the presentation of antigens to T cells. The subset of thymosin beta 4-positive oligodendrocytes is antigenically distinct and may play a role in the immune surveillance of the central nervous system or the demyelinating processes induced by antigen-presenting activated macrophages. PMID- 3085578 TI - Pathogenesis of exercise-induced asthma: implications for treatment. AB - Although the clinical features of exercise-induced asthma (EIA) have been clearly described, the pathophysiology is incompletely understood. This review addresses some of the current concepts about the pathogenetic mechanisms of EIA and their implications for treatment of this problem. PMID- 3085579 TI - Pulmonary function of the transplanted human lung. AB - Satisfactory function of the transplanted lung is an important determinant of long-term survival following combined heart and lung transplantation. Furthermore, assessment of respiratory function in transplant recipients is one of the few currently available methods of detecting pulmonary rejection. This chapter reviews the available data on the function of the transplanted lung based on the first four years of the Stanford experience. PMID- 3085580 TI - Islet transplantation in treating diabetes. AB - Remarkable progress made in the past few years has brought pancreatic islet transplantation to the threshold of human clinical trials. Islet transplants have reversed diabetes in experimental animals and prevented or reversed early diabetic complications in the recipients. Methods have been developed that prevent rejection of islets transplanted across major histocompatibility barriers in rodents without requiring the continuous use of immunosuppressive drugs to maintain the transplants. A new method has been developed for isolating 40% of the islets from a single human pancreas. Based upon these accomplishments, the first phase of human clinical trials on islet transplantation was initiated during the past few months. PMID- 3085581 TI - Aluminum and renal osteodystrophy. AB - Evidence has emerged over the last several years indicating that aluminum accumulation in patients with chronic renal failure can cause certain forms of renal osteodystrophy, in particular osteomalacia and an aplastic lesion. The lines of evidence include epidemiological associations, chemical measurement and histological staining of bone aluminum, animal models of aluminum loading, and a favorable response to the removal of aluminum by chelation therapy. The primary sources of aluminum are dialysate solutions prepared from water with a high aluminum content and the oral ingestion of aluminum-containing phosphate binders. Desferrioxamine, a chelating agent with a high affinity for aluminum, can be used to remove aluminum during dialysis by increasing ultrafilterable plasma aluminum; preliminary results show that symptomatic patients markedly improve, both clinically and in their bone histology, after long-term chelation therapy with desferrioxamine. Treating water to ensure that aluminum levels are appropriately reduced in dialysate and the development of non-aluminum-containing phosphate binders are necessary to prevent aluminum-related osteodystrophy. PMID- 3085582 TI - Prostaglandin biosynthesis and its compartmentation in vascular smooth muscle and endothelial cells. AB - PGI2 is the major, if not the only, eicosanoid formed by smooth muscle and endothelial cells of large arteries and veins. PGI2 is not the major prostanoid synthesized by microvessels. Different stimuli elicit prostanoid production by smooth muscle and endothelial cells. PGI2 is formed at several subcellular sites within smooth muscle and perhaps endothelial cells, but the consequences of this highly unusual distribution are unknown. PGI2 formed by the endothelium can exit on the luminal surface to modulate the functions of circulating blood cells, and probably on the abluminal surface to relax underlying smooth muscle. PGI2 formed by smooth muscle probably acts only upon smooth muscle cells. PMID- 3085583 TI - Cutaneous temperature receptors. AB - Specific thermoreceptors comprise an electrophysiologically distinct class of cutaneous receptors with a morphological substrate (free nerve endings) and plausible transduction mechanism (electrogenic Na pump with or without auxiliary temperature-dependent processes). Because responses to thermal and mechanical stimuli converge along the neural pathway, we have difficulty explaining the purity of cold and warm sensations; participation of dual-modality receptors in sensory discrimination cannot be ruled out. The field is now at a point where a leap in understanding would be achieved by intracellular recordings from the sensory receptor (for which patch clamp studies on isolated neuronal elements may provide the necessary technology) and from continued analysis of what information is lost and what retained in passage from one synapse to the next along the thermal pathway. PMID- 3085584 TI - In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone. AB - The in vitro activity of Ro 23-6240 (AM833), 6,8-difluoro-1-(2-fluoroethyl)-1,4 dihydro-4-oxo-7(4-methyl-1-piper azinyl) quinolone-3-carboxylic acid, was compared with those of norfloxacin, enoxacin, ofloxacin, and ciprofloxacin. Ro 23 6240 inhibited the majority of Enterobacteriaceae isolates at a concentration of less than or equal to 0.5 microgram/ml. It was especially active against Shigella sp., Salmonella sp., Escherichia coli, and Yersinia enterocolitica, with an MIC for 90% of the strains of less than or equal to 0.12 microgram/ml. The MIC for 90% of the strains was 1 microgram/ml for Serratia marcescens and 8 micrograms/ml for Pseudomonas aeruginosa. Staphylococcus aureus isolates, including methicillin resistant strains, were inhibited by less than or equal to 1 microgram/ml. Streptococcal and anaerobic species were inhibited by 8 to 16 micrograms/ml. Ro 23-6240 inhibited beta-lactamase-producing bacteria resistant to broad-spectrum cephalosporins. The overall activity of Ro 23-6240 was similar to those of enoxacin, norfloxacin, and ofloxacin, but less than that of ciprofloxacin. The frequency of spontaneous resistance was low, although resistant bacteria could be isolated by repeated subculture. The activity of Ro 23-6240 was decreased in the presence of magnesium at concentrations similar to those present in urine. PMID- 3085585 TI - Vancomycin hypersusceptibility in Neisseria gonorrhoeae isolated from patients involves diverse mutations. AB - We investigated the genetic determinants of hypersusceptibility to vancomycin and erythromycin found in Neisseria gonorrhoeae strains isolated from patients. In terms of resistance (highest concentration of antibiotic permitting growth), the levels of vancomycin resistance of six strains ranged from 0.2 to 1.0 microgram/ml, and the level of erythromycin resistance of these strains was 0.02 or 0.05 micrograms/ml. DNA from these strains was used to introduce their hypersusceptibility determinants into partially isogenic derivatives of N. gonorrhoeae 89 which initially had wild-type levels of resistance to vancomycin (greater than or equal to 3.0 micrograms/ml) and erythromycin (greater than or equal to 0.1 microgram/ml). The recombination frequencies found in reciprocal transformation tests of six isogenic strains indicated that the mutations responsible for vancomycin hypersusceptibility were located at different sites. The transformants selected for increased resistance to vancomycin were also resistant to erythromycin. This evidence, together with DNA concentration response curves, indicated that the mutations affected either one gene locus or closely linked loci. The recombination indices obtained in crosses between our hypersusceptible strains and DNAs from reference strains carrying the envelope mutations env-1, env-2, env-3, and env-10 showed that the mutation (designated env-12) responsible for erythromycin hypersusceptibility in one strain (89-954) was located in close proximity to env-2. The determinant of vancomycin hypersusceptibility in strain 89-954 was distinct from env-12, but the two were linked. In the other five isogenic strains, the hypersusceptibilities to both vancomycin and erythromycin could be annulled by spontaneous mutations in a locus provisionally designated vel because of its likely effects on the envelope. Vel+ mutants obtained by selection with either vancomycin alone or erythromycin alone gained increased resistance to both antibiotics. PMID- 3085586 TI - Specific hemoperfusion through agarose acrobeads. AB - Agarose acrobeads were produced by encapsulating polyacrolein microspheres (acrobeads) of 0.2 micron average diameter within an agarose matrix. Crosslinked agarose acrobeads of diameters ranging from 0.5 to 0.8 mm were found to be optimal spheres for specific hemoperfusion purposes. Agarose provides the biocompatibility and mechanical strength of the agarose acrobeads. Acrobeads contain a high aldehyde-group content through which various amino ligands, i.e., proteins, antigens, antibodies, enzymes, and so on, can be covalently bound in a single step under physiological pH (or other pH). Thus, antibodies, antigens, or toxic materials may be directly removed from whole blood by hemoperfusion. During in vitro and in vivo hemoperfusion trials, the content of erythrocytes, leukocytes, and thrombocytes was essentially unaltered. Likewise, a battery of the soluble blood components (Cl-, K+, Na+, Ca2+, PO3/4-), total proteins, albumin, and C'4 component of the complement cascade, as well as the enzymes SGOT, LDH, and alkaline phosphatase, remained constant within narrow limits during the hemoperfusion procedure. The chemical and physical structure of the beads is stable; neither acrolein nor bead fragments were detected in hemoperfusion trials. Similarly, leakage of antibody bound to the agarose acrobeads into the blood is insignificant. Thus far, we have demonstrated the efficacy of the crosslinked agarose acrobeads for extracorporeal removal of "unwanted" substances from whole blood in the following systems: (a) removal of specific antigens (digoxin or paraquat removal with antidigoxin or antiparaquat antibodies bound to the acrobeads, respectively), (b) removal of specific antibody (antiBSA) removal with BSA bound to the beads), (c) removal of immune complexes (BSA-antiBSA complex removal with C1q bound to acrobeads), and (d) removal of specific metals (removal of iron with deferoxamine bound to the agarose acrobeads). PMID- 3085587 TI - Biodegradation of chlorinated ethenes by a methane-utilizing mixed culture. AB - Chlorinated ethenes are toxic substances which are widely distributed groundwater contaminants and are persistent in the subsurface environment. Reports on the biodegradation of these compounds under anaerobic conditions which might occur naturally in groundwater show that these substances degrade very slowly, if at all. Previous attempts to degrade chlorinated ethenes aerobically have produced conflicting results. A mixed culture containing methane-utilizing bacteria was obtained by methane enrichment of a sediment sample. Biodegradation experiments carried out in sealed culture bottles with radioactively labeled trichloroethylene (TCE) showed that approximately half of the radioactive carbon had been converted to 14CO2 and bacterial biomass. In addition to TCE, vinyl chloride and vinylidene chloride could be degraded to products which are not volatile chlorinated substances and are therefore likely to be further degraded to CO2. Two other chlorinated ethenes, cis and trans-1,2-dichloroethylene, were shown to degrade to chlorinated products, which appeared to degrade further. A sixth chlorinated ethene, tetrachloroethylene, was not degraded by the methane utilizing culture under these conditions. The biodegradation of TCE was inhibited by acetylene, a specific inhibitor of methane oxidation by methanotrophs. This observation supported the hypothesis that a methanotroph is responsible for the observed biodegradations. PMID- 3085588 TI - Rapid assay for screening and characterizing microorganisms for the ability to degrade polychlorinated biphenyls. AB - We designed a rapid assay that assesses the polychlorinated biphenyl (PCB) degradative competence and congener specificity of aerobic microorganisms, identifies strains capable of degrading highly chlorinated biphenyls, and distinguishes among those that degrade PCBs by alternative pathways. Prior attempts to assay PCB-degradative competence by measuring disappearance of Aroclors (commercial PCB mixtures) have frequently produced false-positive findings because of volatilization, adsorption, or absorption losses. Furthermore, these assays have generally left the chemical nature of the competence obscure because of incomplete gas chromatographic resolution and uncertain identification of Aroclor peaks. We avoided these problems by using defined mixtures of PCB congeners and by adopting incubation and extraction methods that prevent physical loss of PCBs. Our assay mixtures include PCB congeners ranging from dichloro- to hexachlorobiphenyls and representing various structural classes, e.g., congeners chlorinated on a single ring (2,3 dichlorobiphenyl), blocked at 2,3 sites (2,5,2'5'-tetrachlorobiphenyl), blocked at 3,4 sites (4,4'-dichlorobiphenyl), and lacking adjacent unchlorinated sites (2,4,5,2',4',5'-hexachlorobiphenyl). The PCB-degrative ability of microorganisms is assessed by packed-column gas chromatographic analysis of these defined congener mixtures following 24-h incubation with resting cells. When tested with 25 environmental isolates, this assay revealed a broad range of PCB-degradative competence, highlighted differences in congener specificity and in the extent of degradation of individual congeners, predicted degradative competence on commercial PCBs, and (iv) identified strains with superior PCB-degradative ability. PMID- 3085589 TI - Comparative study of selective media for enumeration of Pseudomonas aeruginosa from water by membrane filtration. AB - In the present study, mPA-D and mPA-E agar, modifications of mPA-C agar that reduce background fecal streptococci that interfere with the differentiation and enumeration of the Pseudomonas aeruginosa colonies grown in other mPA media, are proposed for use in analyzing natural water samples. In addition, the efficiencies of several culture media for the recovery of P. aeruginosa in water after membrane filtration and multiple-tube techniques are compared. The degree of selectivity, precision, efficiency, and sensitivity achieved with the proposed media exceeded that achieved by current methods. Furthermore, they yielded equal rates of accuracy and specificity. Incubation at 36 degrees C resulted in an improved recovery of stressed P. aeruginosa. In conclusion, we propose the use of mPA-D and mPA-E agar, both incubated at 36 degrees C for 24 to 48 h, for analyzing river water and seawater, respectively. PMID- 3085590 TI - Modification of an essential amino group of phosphoenolpyruvate carboxylase from maize leaves by pyridoxal phosphate and by pyridoxal phosphate-sensitized photooxidation. AB - Phosphoenolpyruvate carboxylase from maize leaves was inactivated by pyridoxal 5' phosphate in the dark and in the light. A two-step reversible mechanism is proposed for inactivation in the dark, which involves the formation of a noncovalent complex prior to a Schiff base with amino groups of the enzyme. Spectral analysis of pyridoxal 5'-phosphate-modified phosphoenolpyruvate carboxylase showed absorption maxima at 432 and 327 nm, before and after reduction with NaBH4, respectively, suggesting that epsilon-amino groups of lysine residues are the reactive groups in the enzyme. A correlation between spectral data and the maximal inactivation obtained with several concentrations of inhibitor allowed us to establish that the incorporation of 4 mol of pyridoxal 5'-phosphate per mole of holoenzyme accounts for total inactivation. The absence of modifier bound to phosphoenolpyruvate carboxylase when the modification was carried out in the presence of phosphoenolpyruvate and MgCl2 suggests the existence of an essential lysine residue at the catalytic site of the enzyme. Modification of phosphoenolpyruvate carboxylase in the light under an oxygen atmosphere resulted in an irreversible inactivation, which was completely protected by phosphoenolpyruvate and MgCl2. Spectral analysis of the photomodified enzyme showed an absorption peak of 320 nm, suggesting light mediated addition of a nucleophilic residue (probably an imidazole group) to the pyridoxal 5'-phosphate-lysine azomethine bond. PMID- 3085591 TI - Chorismate mutase isoenzymes from Sorghum bicolor: immunological characterization. AB - Highly purified fractions of chorismate mutase 1 and 2 from etiolated seedlings of Sorghum bicolor were used as the antigen for antibody production in BALB/c mice. Tests for antigen-antibody complex formation were made by immunodiffusion, immunoprecipitation, and enzyme-linked immunosorbent assay (ELISA). These tests indicated the presence of specific antibodies for each isoenzyme in their antisera. However, in the same tests, no cross-reaction was found between chorismate mutase 1 and 2 and their antisera. This indicates no immunological similarity between the two isoenzymes of chorismate mutase from sorghum. PMID- 3085592 TI - Calmodulin-independent inhibition of platelet phospholipase A2 by calmodulin antagonists. AB - We tested the effects of calmodulin, two types of calmodulin antagonists, and various phospholipids on the phospholipase A2 activities of intact platelets, platelet membranes, and partially purified enzyme preparations. Trifluoperazine, chlorpromazine (phenothiazines) and N-(6-amino-hexyl)-5-chloro-1 naphthalenesulfonamide (W-7), at concentrations which antagonize the effects of calmodulin, significantly inhibited thrombin- and Ca2+ ionophore-induced production of arachidonic acid metabolites by suspensions of rabbit platelets and Ca2+-induced arachidonic acid release from phospholipids of membrane fractions, but not phospholipase A2 activity in purified enzyme preparations. The addition of acidic phospholipids, but not calmodulin, stimulated phospholipase A2 activity in purified enzyme preparations while decreasing its Km for Ca2+. The dose response and kinetics of inhibition by calmodulin antagonists of acidic phospholipid-activated phospholipase A2 activity in purified preparations were similar to those of Ca2+-induced arachidonic acid release from membrane fractions. Calmodulin antagonists were also found to inhibit Ca2+ binding to acidic phospholipids in a similar dose-dependent manner. Our results suggest that the platelet phospholipase A2 is the key enzyme involved in arachidonic acid mobilization in platelets and is regulated by acidic phospholipids in a Ca2+ dependent manner and that calmodulin antagonists inhibit phospholipase A2 activity via an action on acidic phospholipids. PMID- 3085594 TI - Pyruvate kinase and total protein are regulated differently during growth of P 815 mastocytoma cells. AB - Total protein content of P-815 mastocytoma cells decreases and then increases in response to initiation of a new growth cycle. As the level increases, the rate of synthesis declines. Both events occur prior to any decrease in the rate of cellular proliferation. These temporal relationships indicate that the rate of protein synthesis reflects the intracellular concentration of protein rather than the cellular growth rate, as has been hypothesized. Pyruvate kinase protein metabolism differs from that of total protein in three ways: (a) accumulation does not stop, (b) the rate of synthesis does not decrease, and (c) only the rate of pyruvate kinase degradation is altered by a factor present in conditioned media. These observations suggest that there are specific mechanisms regulating pyruvate kinase at a post-transcriptional level. PMID- 3085593 TI - Purification and characterization of purple acid phosphatase from developing rat bone. AB - Tartrate-resistant acid phosphatase active on nucleoside di- and triphosphate substrates was isolated from developing rat bone and purified 2500-fold. The enzyme concentration had a purple coloration and activity that was sensitive to reducing agents. Mild reducing agents such as ferrous ion and ascorbic acid caused loss of purple color and increased activity toward substrates severalfold; however, a strong reductant such as dithionite caused loss of both color and activity which were partially restored by addition of ferrous ion and ascorbic acid. Enzyme activity was homogeneous with protein during the final gel permeation steps of chromatography and gave an apparent molecular size of about 40,000 Da. Determination of iron in the most pure preparation revealed the presence of 1.3 atoms of iron per molecule of the tartrate-resistant enzyme E2. Other properties of the purified enzyme include a pI of approximately 9.5 and sensitivity to inhibition by ions of copper, zinc, fluoride, and molybdate. Antibody prepared to the pre-concanavalin A (Con A)-Sepharose purified enzyme reacted with all protein from the Con A step, but it did not react with tartrate sensitive acid phosphatase from rat bone or with potato acid phosphatase. Purple acid phosphatase from rat bone has many properties that parallel the iron containing purple acid phosphatases from rat spleen, bovine spleen, and pig uterine secretions. PMID- 3085595 TI - [Study of chemotherapy in the field of internal medicine--clinical experience with SF-SP]. AB - An SF-SP Tegafur spansule preparation was administered to 26 patients with advanced cancer (24 evaluable), and the clinical effectiveness and toxicity were studied. In most of cases, daily dosages of 800 mg were administered in two parts, in a few cases, daily dosages of 1,000 mg or 1,200 mg were given. Clinical effectiveness: The evaluation of effectiveness was based on the Koyama-Saito group criteria. Of the 24 evaluable cases, PR was observed in 3 cases of gastric cancer, one of colon cancer, and one of liver cancer, a total of 5 cases (20.8%). In these 5 cases the daily dosage was 800 mg, and the median duration of PR was 51 days. TOXICITY: TOXICITY was observed in 3 (11.5%) of the 26 cases. PMID- 3085596 TI - [Anti-tumor activity of human recombinant TNF against human malignant glioma cell lines and combined effect with Hu INF-beta]. AB - Human TNF was detected fairly recently and at present the anti-tumor activity of human recombinant TNF is being examined against various malignant tumors of human origin. In the present study, we report the anti-tumor activity of recombinant human TNF against human malignant glioma cell lines in vitro and in vivo, in addition to its combined effects with HuIFN-beta. The in vitro study was conducted as follows. Thirteen human glioma cell lines were exposed to 100 U/ml TNF, 1,000 IU/ml HuIFN-beta, or both, and the suppression rate was calculated on days 3, 5 and 7. In the in vivo study, nude mice carrying a human glioma cell line, KMS II, in the subcutaneous tissues were divided into groups and drugs were administered intratumorally as described below. 1) control, 2) TNF 5,000 U single administration, 3) TNF 5,000 U, intermittently administered (once/week for two weeks), 4) TNF 5,000 U, continuously administered (3/week for two weeks), 5) HuIFN-beta 50 X 10(4) IU (3/week for two weeks), and 6) combination of 4) with 5). Results of the in vitro study revealed some suppressive effects on proliferation of tumor cells on day 7 in all 13 glioma cell lines examined with 100 U/ml TNF. And also, especially in 8 of 13 cell lines, the suppression rate was more than 30%. The suppressive effects of TNF were augmented by combined use of HuIFN-beta in all cell lines, giving a range of suppression of 67.8 to 99.3%. The in vivo study revealed that the mean tumor weight ratios (control = 100%) on day 19 (the end of the experiment) were as follows; single administration of TNF: 41.3%, intermittent: 46.7%, continuous: 26.7%, HuIFN-beta: 65.9%, combination: 18.5%. Statistical analysis disclosed significant suppressive effects on tumor proliferation between the control group and 3 TNF-administered groups (single, intermittent, and continuous) and that suppression in the continuously administered group was more severe in comparison with the group given single administration. Moreover, it was suggested that combination therapy with TNF and Hu IFN-beta was more effective than a single therapy with TNF only or HuIFN-beta only. From the results described above, it was found that human recombinant TNF had some cytotoxic effects against human malignant gliomas in vitro and in vivo, although the degree of cytotoxicity was not always higher in comparison with the effects of TNF. PMID- 3085597 TI - [Adjuvant therapy of gastric cancer in the literature from 1980-1984]. AB - A literature survey was conducted regarding adjuvant therapy for surgical cases of gastric cancer. A total of 66 papers published on a world wide basis in the 5 years from 1980 through 1984 were collected. Forty-three papers (65%) were published by Japanese researchers, of which only 17 were written in English. Adjuvant therapy was regarded as being effective in about 60% of the papers. The main drugs achieving effective adjuvant chemotherapy were mitomycin C (M), 5-FU (F), Tegafur, MF, and MFC(M+F+cytosine arabinoside). The cases yielding an effective result were mainly patients who had undergone radical surgery for stage II or III gastric cancer. The doses used for adjuvant chemotherapy were slightly less than the doses used for chemotherapy of advanced gastric cancer in internal medicine. The incidences of adverse effects of the adjuvant chemotherapy were almost the same as those encountered in internal medicine, and severe complications occasionally developed. Some recent reports observed that efficacy of adjuvant chemotherapy was increased by intensive therapy in the immediate postoperative period and by maintenance therapy over the long term. PMID- 3085598 TI - Bullous pemphigoid antibodies. PMID- 3085599 TI - Diffuse varioliform gastritis. AB - Diffuse varioliform gastritis in a 10 year old girl is reported. The girl has been followed for four years. Biopsy specimens taken before and after three months' treatment with sodium cromoglycate showed a considerable fall in chronic inflammatory infiltrate. A rapid clinical improvement was also observed. PMID- 3085600 TI - Comparative aspects of Aroclor 1254 toxicity in adult cynomolgus and rhesus monkeys: a pilot study. PMID- 3085601 TI - Bioaccumulation of polychlorinated biphenyls and metals from contaminated sediment by freshwater prawns, Macrobrachium rosenbergii and clams, Corbicula fluminea. PMID- 3085602 TI - Chemical stability of mitomycin C in culture medium with and without fetal calf serum as determined by high pressure liquid chromatography and mass spectrometry. PMID- 3085603 TI - Cost-effectiveness of fine needle biopsy of the breast. AB - Although fine needle aspiration (FNA) biopsy of the breast has been shown to be a safe and accurate technique, many surgeons question whether it is reliable enough to replace excisional biopsy. If FNA biopsy is followed by excisional biopsy for confirmation, it would seem that the cost of diagnostic work-up would be increased. In this study, however, the authors show that the major economic benefit of FNA biopsy is not that it replaces excisional biopsy, but that it allows the surgeon to triage which patients should have a 1-stage inpatient procedure with frozen section and which patients should have an excisional biopsy as an outpatient under local anesthesia. Over the past 2 years, the average cost at the East Carolina University School of Medicine of excisional outpatient biopsy (negative) was +702 +/- 348; inpatient biopsy (negative) was +1410 +/- 262; inpatient 1-stage procedure (positive) was +4135 +/- 361; and outpatient biopsy (positive) followed by inpatient procedure was +4822 +/- 586. The authors' last 100 FNA biopsies were read as 23 positive, three suspicious, 65 negative, and nine insufficient. There were no false-positives and four false-negatives, for a sensitivity of 87%, specificity of 100%, and accuracy of 96%. Using the above figures, it is possible to calculate the cost per case if all 100 cases had been biopsied by the 1-stage inpatient technique (+2227), by the 2-stage outpatient method (+1938), or guided by the FNA biopsy where positive and suspicious readings are followed by an inpatient 1-stage procedure and negative and insufficient readings followed by an outpatient 2-stage procedure (+1759). Since the FNA biopsy costs +75, it resulted in a savings per case of +393 over routine inpatient biopsy and +104 per case over routine outpatient biopsy. Computer analysis revealed that the FNA biopsy would still be economically favorable if the sensitivity of the test fell as low as 37%, the specificity as low as 80%, or if the percentage of cases of cancer in the population biopsied fell as low as 13%. Since FNA biopsy is cost effective even when followed by an excisional or frozen section biopsy for confirmation, it would be safe and reasonable to expand its use to smaller hospitals where the personnel may be initially less experienced with the technique. PMID- 3085604 TI - Cerebral carbon dioxide reactivity during nonpulsatile cardiopulmonary bypass. AB - Five patients undergoing extensive cerebral monitoring during cardiopulmonary bypass (CPB) procedures were subjected to studies on cerebral CO2 reactivity during nonpulsatile CPB. The cerebral monitoring included recording of arterial blood pressure (BP), central venous pressure (CVP), epidural intracranial pressure (EDP), cerebral electrical activity by a cerebral function monitor (CFM), and middle cerebral artery (MCA) flow velocity by transcranial Doppler technique. The cerebral perfusion pressure (CPP) was thus continuously recorded (CPP = BP - EDP). During steady-state CPB with constant hematocrit, temperature, and arterial carbon dioxide tension (PaCO2), MCA flow velocity varied with changing CPP in a pressure-passive manner, indicating that the cerebral autoregulation was not operative. During moderately hypothermic (28 to 32 degrees C), nonpulsatile CPB, with steady-state hematocrit, temperature, and pump flow, we deliberately and rapidly changed PaCO2 for periods of 1 or 2 minutes by increasing gas flow to the membrane oxygenator, thereby testing the cerebral CO2 reactivity. Nineteen CO2 reactivity tests, performed at CPP levels ranging from 17 to 75 mm Hg, disclosed that the cerebral CO2 reactivity decreased with CPP, especially with CPP levels below 35 mm Hg. In these patients, concomitant changes in CPP during the CO2 reactivity test could be compensated for by adjusting the observed change in MCA flow velocity. The corrected CO2 reactivity values obtained in this way ranged from below 1.0 (observed at CPP levels below 20 mm Hg) to a 3.0 to 4.5% X mm Hg-1 change in PaCO2 (observed at CPP levels above 35 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085605 TI - [Repair of rheumatic mitral lesions by transfer of a segment of the posterior valve with its chordae onto the anterior valve]. AB - Since 1981, 100 patients have undergone mitral valve repair alone or in association with aortic or tricuspid valve surgery. The basic technique used was that described by Carpentier. However, in 13 of these patients, the repair was performed by a technical innovation consisting in transferring a one to two centimetres segment of the posterior leaflet with its chordae to the anterior leaflet. The lesions in which this particular technique was required were extensive chordal rupture of the anterior leaflet (5 cases), localised retraction of the surface of the anterior leaflet (2 cases), and perforation near the valve free edge due to endocarditis (1 case). The valvular disease was due to rheumatic fever in all cases. None of the patients had active endocarditis. The age of the patients varied from 4 to 60 years. Eight patients were under 15 years of age. Postoperative echocardiography and pulsed Doppler studies showed results comparable to the other patients who had undergone mitral valve repair although the valvular lesions were more severe in this particular group of patients. Only one patient had a poor operative result and had to be reoperated. PMID- 3085606 TI - [Double fulguration of the bundles of His and Kent for recurrent tachycardia in Wolff-Parkinson-White syndrome]. AB - A 59 year old patient with a left postero-septal Kent bundle had daily attacks of reciprocating tachycardia resistant to anti-arrhythmic therapy and was referred for catheter ablation. Kent bundle activity was recorded in the proximal part of the coronary sinus. An endocavitary electric shock delivered at this site suppressed conduction through the Kent bundle for several minutes. Catheter ablation of the His bundle (2 X 200 joules) was then attempted suppressing anterograde conduction for 2 days, after which conduction was reestablished and the reciprocating tachycardia recurred. A second session of catheter ablation was carried out and 2 X 200 joules shocks were delivered in the coronary sinus and 4 to the Bundle of His. Complete anterograde and retrograde atrioventricular block was obtained. Two weeks later, the patient recovered anterograde conduction through the accessory pathway. Retrograde conduction through the Kent bundle was decremental, RP' lengthening with increasing heart rate. Conduction was detected in the His bundle but was insufficient to give rise to reciprocating rhythm. After one year's follow-up the patient was asymptomatic without treatment. Catheter ablation of physiological or accessory conduction pathways provides a valuable alternative to surgical treatment of pre-excitation pathways in the WPW syndrome resistant to medical therapy. PMID- 3085607 TI - [Coronary vasomotor activity in man. Description of a method of quantification and normal values]. AB - The role of vasomotor tone is important in coronary pathology but it has not yet been quantified. The aim of this study was to evaluate the normal maximal variation of diameter between vasoconstriction and vasodilation or the coronary vasomotor capacity: greater diameter-smallest diameter/smallest diameter %. This was performed by two successive pharmacological tests, ergometrine and isosorbide dinitrate (ISDN), the doses of which and modes of administration were defined in a group of 70 patients: Contrast medium: no variations were observed after 5 opacifications at a least 2 minute intervals in 6 patients. Ergometrine test: a single 0.4 mg dose (6 patients) gave a maximal response equal to that obtained with progressive increments 0.1, 0.2, 0.3, 0.4 mg (9 patients). Two opacifications at 3 and 5 minutes were adequate to assess the vasoconstriction with an underestimation of less than 3% compared with a 10 minute control. ISDN test: 3 mg was the maximal haemodynamically well tolerated dose in the majority of patients. This dose gave the same response whether administered by intracoronary (18 patients) or intravenous injection (10 patients). Maximal vasodilatation was obtained after 2 to 4 minutes. A single coronary opacification 2 minutes after injection of ISDN underestimated the vasomotor capacity by 9.3% compared to that calculated after 5 opacifications performed over a 10 minute period. We propose the following protocol: intravenous injection of 0.4 mg of ergometrine with 2 opacifications of the coronary arteries after 3 and 5 minutes respectively. This followed by intravenous or intracoronary injection of 3 mg of ISDN followed by opacification 2 minutes later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085608 TI - [Infranodal chronic auriculo-ventricular block in subjects under 50 years of age]. AB - The aetiology and evolution of chronic infranodal atrioventricular block (AVB) of young patients are not well known: are they the first sign of subclinical myocardial disease which can only be diagnosed by long term follow-up or do they represent isolated degenerative disease of the conduction tissue (Lenegre's disease)? Eighteen patients (15 men, 3 women) aged 25 to 49 years (average 41.5 years) were followed up for periods of 2 to 20 years (average 7.33 years) after pacemaker implantation for syncopal AVB. Follow-up was focused on the evolution of the conduction defects and the cardiovascular status. The patients were divided into two groups at the initial assessment: Group I: 15 patients with documented AVB; Group II: 3 patients in whom all basal recordings showed sinus rhythm (SR). Apart from one patient with an early non-ischaemic dilated cardiomyopathy, there was no previous cardiovascular disease. There was no history of ischaemic heart disease, drug effects, infection or inflammation in favour of an acute AVB. Three patients had permanent AVB, either 2nd degree with bundle branch block (N = 2) or 3rd degree block (N = 1). The other 15 patients were in sinus rhythm with bundle branch block: left bundle branch block (LBBB) in 5 cases, right bundle branch block (RBBB) in 3 cases; RBBB with left anterior hemiblock in 5 cases, RBBB and left posterior hemiblock in 2 cases. Paroxysmal AVB was recorded in 12 of these 15 patients on at least one occasion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085609 TI - [Indications and results of surgery in native valve infectious endocarditis. Apropos of 104 surgically-treated cases]. AB - From 1972 to 1984, 104 cases of aortic valve infectious endocarditis were treated surgically. The average age of the patients was 40 years and the majority were men (69/104). Forty patients had no previous cardiac disease; 44 patients had documented valvular heart disease, which was unlikely in the remaining 20 patients. There were 16 mitral valve, 55 aortic valve, 1 tricuspid, 30 mitro aortic, 1 mitro-tricuspid and 1 mitro-aorto-tricuspid valve infections. Aerococcus viridans was isolated in only 4 out of 71 positive cultures: the prevalence of the infecting organisms was otherwise normal (30 staphylococcus, 30 streptococcus, 7 rare organisms). Forty one patients were operated because of haemodynamic deterioration, 13 for resistant infection and 13 for an association of both indications; 37 patients were operated for embolism or threatening vegetations. Eight patients were in functional Class I, 26 in Class II, 52 in Class III and 17 in Class IV. The patients were divided into 4 groups according to the degree of surgical emergency (26 extremely urgent, 26 semi urgent, 32 controlled endocarditis and 20 chronic endocarditis). The actuarial survival rate was 70% at 5 years. Poor prognostic factors were the presence of previous valve disease, the isolation of a staphylococcus and an aortic valve localisation. The degree of emergency and the precise surgical indication did not seem to be important. Most patients at long term were in functional Classes I or II. There was no preferential indication for bioprosthetic or mechanical valve replacement in endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085610 TI - [Infectious endocarditis surgically-treated in the active phase. Apropos of 46 cases]. AB - The clinical and microbiological characteristics, the surgical indications and procedures, the evolution and the principal prognostic factors were reviewed in 46 cases of infectious endocarditis operated in the active phase. Using this date, the authors try to determine the optimal time for surgery during the acute active phase of infectious endocarditis. The study population comprised 28 men and 18 women aged 7 to 64 years (average age: 30). The patients were selected on strict criteria: positive blood cultures during the 48 hours prior to surgery (29 cases), positive valve or valve prosthesis culture (15 cases), the presence of an active cardiac abscess at surgery (7 cases), the presence of a large number of bacteria on histological examination of the valve (17 cases). The patients were divided into two groups: those with endocarditis of native valves (27 cases) and those with endocarditis on prosthetic valves (19 cases). The preoperative clinical features included all the classical signs of IE but congestive cardiac failure was particularly prevalent (62% of cases). Microbiologically, most cases of native valve endocarditis (67%) were due to sensitive organisms (streptococci) whilst the more virulent organisms (staphylococci, gram-negative bacteria and fungi) were observed in prosthetic valve endocarditis (64% of cases). The commonest surgical indication was haemodynamic deterioration (30 cases). The indications were mixed in 15 cases but only one case was operated for uncontrolled infection alone in this series. The surgical procedure was technically complex in 6 cases. Operative mortality was high (18 cases, 39%). The main cause of death was low cardiac output (13 cases).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085611 TI - [Mitral insufficiency, excluding ruptured papillary muscles, in the acute phase of posterior primary infarction. Anatomical study]. AB - Mitral regurgitation (MR) was demonstrated by water testing valve closure in 23 out 46 cases of patients dying in the 8 days following primary posterior wall infarction due to occlusion of the right coronary or left circumflex arteries (normal valves and chordae; no chronic fibrosis of the papillary muscle). MR was less common with right coronary artery occlusion (14 out of 32; 44%) than with left circumflex occlusion (9 out of 14; 64%). Two anatomical conditions seem to be necessary (all cases but one) for MR to occur: ischaemic necrosis of all or nearly all of the posterior papillary muscle and its base of implantation on the posterior wall. These valvular leaks are usually mild (papillary muscle rupture was excluded) and do not seem to play a major role in the haemodynamic deterioration of these patients, the majority of whom die of irreducible cardiac failure caused by extensive myocardial destruction. The mechanism of the majority of these MR was systolic eversion of the posterior part of the posterior leaflet in the left atrium (6 cases) of the posterior juxtacommissural part of both leaflets (13 cases), of the posterior part of the anterior leaflet (3 cases). Ischaemic destruction of the posterior papillary muscular system and its base of mural implantation (anatomical criteria that we retained) correlated with the occluded artery. PMID- 3085612 TI - [Myocardial contusions. Contribution of scintigraphy using thallium-201. A prospective series]. AB - Traumatic myocardial contusion is observed in 15% of autopsy studies; however, it is much more difficult to detect in survivors. Thirty-two consecutive, unselected patients admitted to the intensive care unit for serious thoracic injuries, underwent Th 201 myocardial scintigraphy in 2 to 4 different projections, 2 to 13 days after admission. The results were interpreted double blind and considered positive when a zone of hypofixation creating a defect greater than 25% was observed. The results were correlated with daily ECG recordings, serum CPK MB levels and echocardiography. Thirteen patients (41%) had abnormal scintigraphy. Border line appearances in 1 case excluded any severe myocardial lesions. The other investigations (56%) were normal. These results did not correlate with the ECG or echocardiographic appearances but a significant relationship was found with serum CPK MB levels (p less than 0.05). Therefore, the first investigations did detect cardiac damage but were not specific for myocardial lesions. Thallium 201 myocardial scintigraphy is superior to other non-invasive investigations. It provides information as to the size of the lesion and, by repeated studies, can differentiate simple myocardial contusion from a true traumatic myocardial infarction. PMID- 3085613 TI - [Nifedipine in the treatment of chronic cor pulmonale]. AB - The effects of a single dose of nifedipine (20 mg sublingual) on the haemodynamics and parameters of tissue oxygenation were assessed by right heart catheterisation and oximetry of mixed arterial and venous blood in 24 patients with pulmonary hypertension secondary to severe chronic obstructive airways disease. The haemodynamic effects of 15 days' oral therapy (30 mg/day) were studied in 10 other patients. Significant improvement in right ventricular pump function (25 p. 100 increase in cardiac index. average reduction of 3 mmHg of right ventricular end diastolic pressure), and lowering of pulmonary hypertension (mean pulmonary artery pressures reduced by an average of 10 p. 100 and total pulmonary resistance by 25 p. 100) were observed after the single dose of nifedipine. This improvement was maintained after oral therapy for 15 days. The significant improvement of tissue oxygenation was reflected by an increase in oxygen transport (+ 24 p. 100), in the coefficient of delivered oxygen (+ 19 p. 100), in the oxygen partial pressure (+ 4 p. 100) and saturation (+ 3 p. 100) in the mixed venous blood. Arterial lactate concentrations fell by about 28 p. 100. In addition, a moderate fall in ppO2 and arterial saturation was observed due to a weak shunt effect which was more than compensated by the increase in cardiac output, and especially by the increase in the coefficient of relieved oxygen. These results show that nifedipine may be a valuable addition in the treatment of cor pulmonale secondary to chronic obstructive airways disease by improving right ventricular haemodynamics and pulmonary circulation and by increasing the quantity of oxygen delivered. PMID- 3085614 TI - [Evaluation of coronary lesions in biventricular inferoposterior infarction]. AB - Fifty-two patients with primary transmural infero-posterior infarcts underwent right heart catheterisation on admission to hospital and coronary angiography between the 7th day and 4th month after onset of symptoms. The patients were divided into two groups A (N = 34) with signs of right ventricular dysfunction on admission indicating biventricular infarction, and B (N = 18) without right ventricular dysfunction classified as isolated LV infarction. No significant differences were observed between the two groups with respect to: global and regional LV function; the incidence of single, double and triple vessel disease; the incidence and location of right coronary artery thrombosis; the incidence and location of lesions of the left coronary tree (LCA, LAD, Cx); the extent of coronary disease (Gensini score); the dominant artery (right coronary/circumflex), the frequency and quality of revascularisation of distal vessels. The only significant differences were the higher incidence of severe lesions (90 p. 100) of the right coronary and circumflex arteries and of stenosis of the first large septal branch of the LAD artery in Group A (p less than 0.05). These results show that the indications for coronary angiography in biventricular inferior infarction are no greater than those in mono LV inferior infarction. This supports experimental data on the physiopathology of RV infarction which demonstrates that except in cases of proximal thrombosis of the right coronary artery, the possibilities of revascularisation from the left coronary tree are limited. PMID- 3085615 TI - [Isolated aortic valve replacement in an advanced stage of cardiac failure. Results and prognostic study apropos of 71 cases]. AB - Between January 1970 and December 1982, seventy-one patients in functional Stage IV of the NYHA classification underwent isolated aortic valve replacement for aortic incompetence (27 cases), aortic stenosis (18 cases) or mixed aortic valve disease (26 cases). Three haemodynamic criteria were chosen: left ventricular ejection fraction less than 40% (average 34 +/- 2%); arteriovenous difference greater than 6 volumes per 100 ml (average 6.7 +/- 0.2 vol.); left ventricular end diastolic pressure greater than 20 mmHg (average 26 +/- 1.3 mmHg). Analysis of the preoperative data defined the clinical profile of these patients: average cardiac index 2.2 +/- 0.07 l/min/m2; 75% had a cardiothoracic index greater than 0.50%; 61% had at least one conduction defect. The average Sokolow index was 50 +/- 2 mm. Twenty seven of the 71 patients died (36%); there were 7 early postoperative deaths (1st month) (10%), mainly due to ventricular arrhythmias (6 out of 7). There were 20 late deaths (31%) on average 52 +/- 8 months after surgery: 70% were of cardiac origin with a predominance of sudden deaths. There were no deaths in the group of patients operated after 1977, probably because of improved techniques of peroperative myocardial protection. The actuarial survival was 72% at 5 years and 63% at 10 years: long term survival was lower in aortic incompetence (25% at 10 years) compared with aortic stenosis (68%) and mixed aortic valve disease (78%). There was a significant relationship between long term survival and cardiothoracic ratio, ejection fraction, the duration of symptoms before surgery and the presence of atrioventricular or left bundle branch block.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085616 TI - [Have vasodilators improved the prognosis of cardiac failure?]. PMID- 3085617 TI - [Comparison of 2 groups of patients hospitalized at 10 years' interval for recent myocardial infarction]. AB - The aim of this study was to compare two groups of patients admitted consecutively to the Coronary Care Unit in 1972-73 (223 cases) and in 1982-83 (243 cases) for recent myocardial infarction, and followed up for at least 15 days, to try and appreciate the influence of changes in treatment which had taken place during this interval on outcome and mortality. The two groups were comparable with regards to age, sex, time of admission with respect to onset of symptoms, previous vascular disease, and principal coronary risk factors. The clinical presentation of myocardial infarction and its common complications (cardiac failure, arrhythmias) were unchanged at 10 years' interval. The only statistically significant but unexplained difference was the lower proportion of posterior infarctions in 1982-1983 compared to 1972-1973. This decrease was partly due to the increased detection of rudimentary infarcts by more specific enzyme methods. The decrease in the proportion of posterior infarcts probably also explained the lower numbers of atrioventricular blocks. Other differences between the two groups were not statistically significant (slight increase in age, fewer women, lower incidence of cardiac failure). The mortality rate was exactly the same at 20.6%, and the causes of death were identical. The results support those of other rare studies of the same subject showing the lack of effect of recent therapeutic innovations on the majority of patients with myocardial infarction. PMID- 3085618 TI - [Tricuspid endocarditis. Value of echocardiography. Developmental data. Apropos of 11 cases]. AB - Clinical and echocardiographic data of 11 patients with tricuspid valve endocarditis (TE) were analysed to determine diagnostic criteria and to study the outcome of this condition. The study population comprised 6 men and 5 women (average age 38.4 +/- 18 years). TE was the only lesion in 9 cases; there was 1 case of associated pulmonary and aortic valve endocarditis, and in the other patient mitral and aortic valve endocarditis was also present. Five patients were heroin addicts. In 5 cases, the causative organism was Staphylococcus aureus. The clinical presentation was usually atypical with a systolic murmur rarely characteristic in 9 patients and signs of right ventricular failure in only 3 patients. On the other hand, 8 patients had one or more episodes of acute pneumonia or typical pulmonary embolism. The diagnosis was established by echocardiography which demonstrated the valvular vegetations. The outcome was favourable in 10 patients, only one of whom required surgical intervention. Two dimensional echocardiography provided valuable information about the evolution of the valvular vegetations, frequently showing regression after medical therapy. PMID- 3085619 TI - [The diagnostic exercise test in coronary disease. Proposal for a more rigorous and efficacious interpretation]. AB - Although exercise stress testing does not allow certain diagnosis of coronary artery disease, its interpretation should not necessarily be vague. By using the Bayes theorem and the many studies available we can now quantify the probability of a correct result for each individual case. Three parameters need to be known to undertake this calculation; the prevalence of the disease and the sensitivity and specificity of the investigation. The prevalence of the disease is beginning to be recognised taking into account the character of the pain. Four groups of increasing prevalence can thereby be defined: absence of chest pain, non-anginal pain, atypical pain and typical pain. Within each of these groups the prevalence of coronary disease is higher in men and increases with age. Information about the prevalence of multivessel disease after infarction is more limited. Only two groups can be distinguished which do not take symptoms, age or sex into consideration. The prevalence is 57% after anterior and 65% after inferior infarction. The sensitivity and specificity of stress testing can be determined by comparison with coronary angiography or, when this is available, by following up the patients. These parameters depend mainly on the methodology which should be strictly defined. When only significant ST depression is considered, the overall sensitivity and specificity of exercise stress testing is 70% and 80% respectively. These results vary according to the particular context; in women, the sensitivity and specificity are 72% and 75% respectively; in asymptomatic subjects the sensitivity and specificity are 50% and 85% respectively. With regards to the detection of multivessel disease after anterior infarction, the sensitivity and specificity are 58 and 85% respectively and after inferior infarction, 85 and 84% respectively. The use of diagnostic probability based on these parameters should lead to unambiguous practical management of patients related to the degrees of probability obtained. The underlying principles of this diagnostic approach cannot be questioned as they are based on a well established mathematical formula. However, much work remains to be done, on the one hand to determine the exact prevalence of coronary disease, and on the other hand to improve the sensitivity of exercise stress testing. PMID- 3085620 TI - [Diagnosis of atrial septal defects by contrast echocardiography with sensitivity increased by coughing]. AB - The aim of this study was to assess the sensitivity of contrast echocardiography in the diagnosis of permanent (atrial septal defects, ASD) and transient (patent foramen ovale, PFO) interatrial communications under basal conditions, after Valsalva manoeuvres and coughing. Sixty-four patients suspected of having defects of the interatrial septum were studied. The results of echocardiography were compared with those of cardiac catheterisation, the classical method of reference. The sensitivity of contrast echocardiography was significantly improved in the diagnosis of PFO by the cough test (100%) compared with contrast echocardiography during spontaneous respiration (55%). Similarly, the cough test increased the sensitivity of contrast echocardiography in the diagnosis of ASD (96% compared to 83%). The specificity was good in both cases, about 90%. The cough test was a better method (98%) than Valsalva manoeuvres (59%) for the potentiation of interatrial right-to-left shunts. The results of echocardiography and catheterisation explain the mechanism of the right-to-left shunt during spontaneous respiration, Valsalva manoeuvres and coughing. The passage of the microbubbles from the right to the left atrium occurs during early systole when the atrioventricular valves are closed. The right-to-left shunt is potentiated by provocative manoeuvres. The demonstration of a right-to-left shunt by contrast echocardiography therefore indicates the presence of an interatrial communication; our results show that this non-invasive technique is a reliable method of diagnosing ASD and PFO. PMID- 3085621 TI - [Monitoring and rehabilitation of heterotopic cardiac transplantation patients during the period of convalescence]. AB - Heterotopic cardiac transplantation is a procedure performed in patients with severe pulmonary hypertension. Surgery is usually preceded by a long period of inactivity. This paper reports the results of a programme of cardiac readaptation, the complications observed, the improvement obtained and the problem replated to the absence of graft innervation. Eight patients who underwent heterotopic cardiac transplantation underwent the readaptation programme. This began with an exercise ECG on which the physical training programme was based. Sessions of respiratory and muscular physiotherapy were also arranged during the same period; a second exercise ECG was performed at the end of the programme to assess progress. Clinical, biological, electrocardiographic and echocardiographic parameters were carefully monitored. The results of the final exercise ECG showed the average maximal work capacity to be 90 watts for 3 minutes. The average increase in heart rate on effort was 25.92%. This was significantly higher than the resting heart rate (p less than 0.01). Two complications were observed during the programme: ventricular fibrillation of the cardiac graft and graft rejection on the 35th postoperative day, diagnosed by echocardiography. Progression of exercise capacity was observed in all patients. The two patients who made the least progress were those who underwent the fewest sessions of physical readaptation. This improvement was mainly related to peripheral muscular fitness. The training programme was well tolerated by all patients; the principal factor limiting an increase in cardiac output on effort was the absence of graft innervation. The heart rate can only be increased by two mechanisms: an increased venous return and raised concentrations of circulating catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085622 TI - [Left ventricular function in dilated cardiomyopathy. Noninvasive determination of end-systolic stress-diameter and shortening fraction-stress relations]. AB - The ejection fraction and fractional shortening are parameters of left ventricular function dependent on the conditions of load. They are not perfect indices of myocardial contractility. The study of the relationships between stress and diameter and fractional shortening and stress in end-systole provides a better means of assessing the contractile state of the myocardium. The relationships between end-systolic stress-diameter and end-systolic stress fractional shortening were studied non-invasively in 10 normal subjects (Group I) and 7 patients with severe dilated cardiomyopathy (Group II). End-systolic longitudinal stress of the left ventricle was calculated from Grossman's formula by coupling automatic measurement of blood pressure (cuff method) with simultaneous M mode recordings guided by 2D echocardiography. The line of regression of end-systolic stress-end-systolic diameter was determined in all cases from a series of 14 points obtained after sublingual administration of 10 mg of isosorbide dinitrate. The line of regression of fractional shortening-end systolic stress was established in both groups by using the values observed under basal conditions and at the peak of action of the isosorbide dinitrate. The following results obtained: Under basal conditions, patients in Group II had greater end-diastolic diameters (69 +/- 8 vs 49 +/- 4 cm, p less than 0.01), greater end-systolic diameters (61 +/- 8 vs 33 +/- 4 mm, p less than 0.001) and higher end-systolic stress (140 +/- 54 vs 67 +/- 13 10(3) dyn/cm2, p less than 0.001). Fractional shortening was lower in Group II than in Group I (12 +/- 5 vs 33 +/- 5%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085623 TI - [Electrophysiologic effects of intravenous carocainide]. AB - The electrophysiological properties of carocainide a new Class I antiarrhythmic agent (Delalande Research Centre) were studied after intravenous injection of 3.5 mg/kg in 5 minutes in 16 patients aged 24 to 66 years. Five minutes after the injection there was a significant increase (p less than 0.01) in the HV (+/- 12.8 +/- 10.5 msec), AH (+ 21.8 +/- 14 msec) and PR intervals (+ 43.8 +/- 24.2 msec) and in the duration of QRS (+ 20.6 +/- 9.9 msec). The anterograde and retrograde Wenckebach points were decreased (-42 +/- 43 bpm and - 52 +/- 36 bpm respectively, p less than 0.05). All these effects reverted progressively 20 minutes after injection and disappeared by the 40th minute, which corresponds to the pharmaco-kinetic profile of the patient. There were no changes in blood pressure, sinus node function or refractory periods except for the retrograde refractory periods which were prolonged (+ 87 +/- 41 msec). Atrial fibrillation was induced in 2 patients and atrial flutter in 2 others by the extrastimulus technique. These arrhythmias could not be reproduced in these 4 patients during the 40 minutes after injection of carocainide. Five other patients with reciprocating nodal tachycardia induced by atrial extrastimuli had their arrhythmia interrupted by the carocainide injection. We conclude that carocainide acts mainly on atrio-ventricular and intra-ventricular conduction. The results obtained in patients with tachycardias suggest that the product is effective in atrial arrhythmias and paroxysmal junctional tachycardia. PMID- 3085624 TI - [Myxoma of the right ventricle. Apropos of 2 cases]. AB - Two cases of primary cardiac tumour are reported. The first was that of a 16 year old girl investigated after the detection of a systolic murmur on routine examination. The clinical signs suggested a diagnosis of pulmonary stenosis. The second case was that of a 36 year old man admitted to hospital for right ventricular failure. Echocardiography revealed right ventricular tumours in both cases and also indicated their size, form, mobility and site of implantation. The outcome of the first case, a fibromyxoma, was favourable with no detectable recurrence after one year. In the second case, the patient unfortunately died of cardiogenic shock in the immediate preoperative period. These two cases emphasise the value of echocardiography in the diagnosis of isolated right ventricular tumours, especially considering the difficulty of clinical diagnosis and the risks of angiocardiography. PMID- 3085626 TI - [Allogeneic bone marrow graft in children]. PMID- 3085625 TI - [Interruption of the aortic arch without patent ductus arteriosus. Apropos of a case associated with partial atrioventricular canal]. AB - The authors report a case of type A interruption of the aortic arch with the subclavian arteries arising from the descending aorta which was of special interest because of the absence of a patent ductus arteriosus. Therefore, the systemic circulation was assured from the carotid arteries which perfused the vertebral arteries retrogradely via the circle of Willis. The association of a partial endocardial cushion defect and hypoplasia of the ventricle explained the surgical failure. A review of the literature of interruption of the aortic arch without a ductus confirmed that this was a rare condition and, paradoxically, well tolerated in the absence of associated malformations. On the other hand, the left ventricular lesions, usually present in the classical forms with patent ductus arteriosus, operated in the neonatal period, increase the operative risk. PMID- 3085627 TI - [Nitrate derivatives and congestive cardiac failure in infants. Pharmacological efficacy of transcutaneous administration devices]. PMID- 3085629 TI - [Immunosuppression by retroviruses in tumors and immune deficiency diseases]. AB - Most retroviruses are immunosuppressive in vitro and in vivo. They are able to enhance virus-induced tumor development and/or to induce acquired immune deficiency syndromes (AIDS) which are characterized by malignant tumors and opportunistic infections. Experimental evidence for the immunosuppressive properties of several type D viruses derived from human cell lines and other retroviruses is presented. PMID- 3085628 TI - Human monoamine oxidase. Lack of brain and platelet correlation. AB - Monoamine oxidase (MAO) exists in two forms, MAO A and MAO B. Both are present in human brain, but the human platelet contains only MAO B. We studied whether individual variations in the activity of human platelet MAO B reflect individual variations in cerebral cortical MAO activities. Optimal conditions were determined for the measurement of MAO activities in both the platelet and cerebral cortex, obtained from 14 patients with epilepsy during clinically indicated neurosurgery. There was no significant correlation between the activities of MAO B in the cerebral cortex and platelets of these patients. Platelet MAO B activities also failed to correlate significantly with cerebral cortical MAO A activities. However, there was a significant positive correlation between cerebral cortical MAO A and MAO B activities. Individual variations in platelet MAO B activities do not reflect individual variations in either cerebral cortical MAO B or MAO A activities in patients with epilepsy who undergo neurosurgery. PMID- 3085630 TI - [Viral tumors in monkeys]. AB - A short review of virus induced tumors in primates is presented. It includes especially the haemoblastoses (lymphomas) and the corresponding viruses (herpesviruses, retroviruses) and shows the value of the animal models for analysis of similar human tumors. PMID- 3085631 TI - Sphingomyelin lipidosis variant with cirrhosis in the pediatric age group. AB - Two children with a variant of sphingomyelin lipidosis had otherwise unexplained cirrhosis that was histologically inactive and appeared to run an indolent course. The primary clinical problems involved the central nervous system, with vertical supranuclear ophthalmoplegia being the most distinctive feature. Biochemical analysis of cultured skin fibroblasts obtained from one of the children revealed that sphingomyelinase activity was 42% of control values. The typical inconspicuous hepatic storage and cirrhosis, coupled with the important morphologic finding of sea-blue histiocytes in the marrow, suggested that in cases of unexplained infantile or childhood cirrhosis the marrow should be closely examined for such histiocytes. Likewise, in cases of sea-blue histiocytes without evident etiology, with or without cirrhosis, this disease should be considered. PMID- 3085632 TI - Atrophie blanche. A disorder associated with defective release of tissue plasminogen activator. AB - Atrophie blanche is a skin disorder characterized by recurrent ulceration and fibrosis. It is one of a group of cutaneous vasculitides associated with decreased blood fibrinolytic activity. We examined pre- and post-venous occlusion plasma from eight patients with atrophie blanche for release of vascular (tissue type) plasminogen activator (t-PA). The average plasma level of releasable t-PA was only 0.03 IU/mL, compared with 0.70 IU/mL for 118 healthy controls. Therefore, the fibrinolytic disorder in atrophie blanche is associated with defective release of t-PA from blood vessel walls. PMID- 3085634 TI - Environmental control systems in chronic care hospitals and nursing homes. AB - Fifteen severely disabled people residing in institutions were provided with a simple environmental control system which performed five different functions. The disabled people used the equipment an average of ten times a day. Two hours of nursing care by nursing staff would have been required to perform these functions. The cost of the equipment was $1.35 a day. Both the residents and the nursing staff reacted favorably to this innovation. The main benefits which resulted were a heightened sense of independence on the part of the disabled people and a reduction of frustration levels of both the residents and the nursing staff. A considerable savings in nursing care was also achieved. PMID- 3085633 TI - Blood levels and half-life of methylmethacrylate after tourniquet release during knee arthroplasty. AB - The blood levels and the half-life of monomeric methylmethacrylate after tourniquet release were studied in nine patients with osteoarthrosis or rheumatoid arthritis of the knee joint, treated with the Townley prosthesis under spinal anesthesia. Several ventricular extrasystoles were monitored in one patient with high blood levels of monomeric methylmethacrylate (119.80 micrograms/ml). The blood levels of monomeric methylmethacrylate ranged between 0.10 and 1.44 microgram/ml in the rest of the patients. The half-life of monomeric methylmethacrylate in vivo was 47-55 min. PMID- 3085636 TI - Effect of fresh-frozen plasma resuscitation on cardiopulmonary function and serum protein flux. AB - The adverse effects of albumin resuscitation on coagulation activity, cardiopulmonary function, and extravascular flux of nonalbumin protein have made fresh-frozen plasma (FFP) an attractive alternate volume expander for hemorrhagic shock. This study addresses the effects of FFP on cardiopulmonary hemodynamics and protein flux. Whole blood was collected three and six weeks before shock, separated into red blood cells (PRBCs) and FFP, and stored. In 24 conditioned splenectomized dogs, resuscitation from reservoir shock of two hours' duration consisted of autologous PRBCs and balanced electrolyte solution (BES) in control dogs and PRBCs, BES, and FFP in plasma-treated dogs. Hemorrhagic shock reduced serum albumin and IgG levels in both groups. Resuscitation with FFP led to a higher cardiac output, left ventricular stroke work (LVSW), and pulmonary capillary wedge pressure (PCWP). The PCWP/LVSW ratio was comparable for both groups. Postshock day 2 serum albumin and IgG levels and lymphatic albumin and IgG concentrations were increased in plasma dogs. Therefore, FFP supplement to PRBC and BES resuscitation does not derange the PCWP/LVSW ratio or reduce intravascular nonalbumin proteins. PMID- 3085635 TI - Heterotopic ossification masquerading as deep venous thrombosis in head-injured adult: complications of anticoagulation. AB - A 26-year-old man manifested clinical signs of a left iliofemoral thrombosis 12 weeks after closed head injury in a motor vehicle accident. The deep vein thrombosis was initially diagnosed by venography and appropriate anticoagulation therapy was instituted. After four days of treatment, there was no significant resolution of signs or symptoms and the circumference of the left thigh had increased with an associated decrease in hemoglobin. A CT scan of the involved thigh revealed hemorrhage and calcification within the quadriceps muscle. In retrospect, it was evident that the hemorrhage and heterotopic ossification had caused compression of the surrounding tissue and vessels thus mimicking a deep vein thrombosis on venography. Clinicians need to be aware of the similarity of the early clinical manifestations of heterotopic ossifications and deep vein thrombosis and the complications which could arise with anticoagulation therapy initiated too early in the course of the disease. PMID- 3085637 TI - Sepsis from triple- vs single-lumen catheters during total parenteral nutrition in surgical or critically ill patients. AB - We prospectively studied the infection rates for 59 triple-lumen (TLC) and 68 single-lumen (SLC) subclavian catheters during the administration of total parenteral nutrition (TPN) to surgical or critically ill patients. A standard protocol was used for catheter insertion and maintenance. The infection control committee determined independently whether patients had catheter-related sepsis, an infected insertion site only, or no catheter infection. The TLCs had an increased incidence of catheter sepsis (19%) compared with the SLCs (3%). Low rates (5% for TLCs and 3% for SLCs) of infected catheter sites only indicated that the catheter care was comparable for both groups. The patients in the two groups were similar but not identical; those with TLCs appeared to be sicker and, therefore, at greater risk to develop catheter sepsis than patients with SLC. However, since TLCs were involved in six times more catheter sepsis than were SLCs, limiting the use of a subclavian catheter to giving TPN only and strict adherence to a TPN protocol are necessary to minimize the risk of catheter sepsis. PMID- 3085638 TI - Prediction of the development of sigmoid ischemia on the day of aortic operations. Indirect measurements of intramural pH in the colon. AB - A deviation in an indirect measurement of intramural pH below the limits of normality (6.86) was used as a diagnostic test for sigmoid ischemia in 25 high risk patients undergoing abdominal aortic operations. The clinical diagnosis of ischemic colitis was made by the attending physicians in only two of the 25, on the day after operation in one and three months after operation in another. In neither was the ischemic colitis considered to have been a causative factor in their subsequent deaths. In contrast, six patients developed pH evidence of ischemia on the day of operation. All six subsequently developed a transient episode of guaiac-positive diarrhea, four developed physical signs consistent with ischemic colitis, and four died. Of 19 who did not develop pH evidence of ischemia, none developed guaiac-positive diarrhea, none developed any signs of ischemic colitis, and none died. Stepwise logistic regression showed the duration of pH evidence of ischemia on the day of operation to be the best predictor for the symptoms and signs of ischemic colitis and for death after operation. PMID- 3085640 TI - A knotty problem with a feeding jejunostomy tube. PMID- 3085639 TI - Hospital stay following biliary tract surgery. A comparison of two community hospitals. AB - An apparent difference in length of postoperative hospitalization following biliary tract surgery at two university-affiliated community hospitals led to a retrospective review of 200 consecutive patients at each hospital. Patient characteristics and surgical practices that potentially affected hospital stay were compared. A highly significant difference was identified in the length of hospitalization between the two institutions. Statistically significant differences in variables that seemed to affect length of stay included the use of nasogastric tubes and abdominal drains and the time interval to the institution of postoperative feedings. Cumulative hospitalization was 517 days shorter at one institution. This was accomplished despite a high percentage of emergent procedures and more frequent involvement of surgical residents. Since hospital stay accounts for the majority of expenditure for surgical treatment of biliary tract disease, shortening postoperative hospitalization can significantly reduce the overall costs. PMID- 3085641 TI - The effect of age on the prostaglandin formation in the rabbit aorta. PMID- 3085642 TI - [Comparative analysis of the neocortex during the ontogenesis of cetaceae and primates]. AB - Comparative ontogenetic investigation of cytoarchitectonics of the cerebral neocortex has been performed in Cetacea and Primates using paraffin frontal and sagittal cerebral sections stained after Nissl. Cerebral hemispheres of dolphins, whales, monkeys and human being have been studied at various periods of prenatal development and in mature individuals. The comparison has been made at similar stages of cytoarchitectonical differentiation of the cortical plate. At two first stages of the prenatal ontogenesis (formation of the cortical plate and its differentiation into layers) there is not any principle differences between the Cetacea and Primates. Peculiarities of the cerebral cortical plate differentiation in the Cetacea (absence of the internal granular layer IV) is determined at the stage of stratification. Similar agranular character of the cerebral cortex differentiation is maintained during the whole subsequent ontogenesis in the Cetacea (heterogenetic type of the neocortex after Brodman). Absence of the layer IV in the cerebral neocortex determines some other principles in the spatial organization of the cortical-subcortical and in the intracortical connections in the Cetacea brain. This is confirmed by modern data of morphological and electrophysiological investigations. Perhaps, a comparatively more simple initial architectonics of the Cetacea brain limited the level of their functional possibilities, the latter is comparable only with anthropoid apes. PMID- 3085643 TI - The diffusion in vitro of fluoride and chlorhexidine in the enamel of human deciduous and permanent teeth. AB - The permeability of human dental enamel was studied by following the diffusion of [51Cr]-ethylenediaminetetraacetate (EDTA), F and [14C]-chlorhexidine using two chamber diffusion cells. The [51Cr]-EDTA served as a marker to control the change in enamel permeability during the diffusion process. An average increase in enamel permeability of about 1.6-fold was recorded following the initial diffusion of the test compounds in the deciduous and permanent enamel. The permeability of deciduous enamel was much higher than that of permanent enamel. For [51Cr]-EDTA and [14C]-chlorhexidine, the average diffusion coefficient was about 30-fold more than in permanent enamel; for F it was 150-fold more. The difference was statistically significant (p less than 0.001). Co-administration of F and [14C]-chlorhexidine showed a higher diffusion rate for each compound than when separately diffused. Whether this is due to a synergetic effect or to increased enamel permeability following the initial diffusion of the compound, or both, is still uncertain. PMID- 3085644 TI - Monocyte chemotactic factor produced by large vessel endothelial cells in vitro. AB - Cultured rabbit aortic and human carotid artery endothelial cells produced a factor that was chemotactic for monocytes but not for neutrophils. Checkerboard analysis showed that the activity was due to chemotaxis and not to chemokinesis. The factor was produced in both serum-containing and serumless media. Treatment with carboxypeptidase and trypsin resulted in inhibition of chemotactic activity, indicating that the factor is a peptide. Medium from cultures of rabbit aortic, human carotid artery, and human umbilical vein endothelial cells previously exposed to beta migrating very low density lipoprotein (beta-VLDL) had substantially more chemotactic activity than medium from untreated cells or cells exposed to low density lipoprotein. beta-VLDL alone had no chemotactic activity. We conclude that large vessel endothelial cells produce a monocyte chemotactic factor that is increased after exposure of the cells to beta-VLDL. PMID- 3085645 TI - Tissue sites of degradation of high density lipoprotein apolipoprotein A-IV in rats. AB - The in vivo metabolism of high density lipoprotein (HDL), labeled by incorporation of 125I-apolipoprotein (apo) A-IV, was studied in the rat and compared with the metabolism of HDL labeled with 131I-apo A-I. The 125I-apo A-IV labeled HDL was obtained by adding small amounts of radioiodinated apo A-IV to rat serum, followed by separation of the different lipoprotein fractions by chromatography on 6% agarose columns in order to avoid "stripping" of apolipoproteins by ultracentrifugation. Under both in vitro and in vivo conditions, the 125I-apo A-IV remained an integral component of HDL and was not exchanged to other lipoproteins, including the ""free" apo A-IV fraction. The serum half-life, measured at between 8 and 28 hours after intravenous injection of labeled HDL, was 8.5 +/- 0.5 hours for HDL apo A-IV and 10.2 +/- 0.7 hours for HDL apo A-I. The tissue sites of catabolism of HDL apo A-IV and HDL apo A-I were analyzed in the "leupeptin-model." Only the kidneys and liver showed a significant leupeptin-dependent accumulation of radioactivity. At 4 hours after injection of 125I-apo A-IV/131I-apo A-I labeled HDL, 3.5% +/- 1.0% and 8.4% +/- 2.0% of HDL apo A-IV and 4.6% +/- 1.3% and 2.6% +/- 0.6% of the HDL apo A-I were accumulated in a leupeptin-dependent process in the kidneys and liver, respectively. Immunocytochemical studies revealed that the renal localization of apo A-IV was intracellular and confined to the epithelial cells of the proximal tubuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085646 TI - Immunochemical characterization of apolipoprotein A-I from normal human plasma. In vitro modification of apo A-I antigens. AB - Two series of monoclonal antibodies (MAB) directed against apolipoprotein A-I (apo A-I) reacted differentially with freshly prepared sera or plasma. MAB from Series 1 were obtained after immunization and screening with purified apo A-I, while those from Series 2 were obtained by immunization with high density lipoprotein (HDL) and screening with both HDL and apo A-I. Series 2 MAB 5F6, 3G10, and 4F7 reacted significantly better with fresh material than material stored at 4 degrees C for longer than 1 month. Conversely, Series 1 MAB 3D4, and 6B8, and Series 2 MAB 2F1 reacted more strongly with the stored preparations. Series 2 MAB 4H1 reacted equally with stored or fresh material. The inability of 3D4 and 6B8 to react with fresh sera or plasma was not due to an inhibitor in the fresh material. Preparation of HDL from serum or plasma and delipidation of this material had no effect on the above phenomena, which appears related directly to apo A-I and not to the interaction of apo A-I with lipids. The variation of immunoreactivity with storage at 4 degrees C was also shown to be unrelated to proteolysis of apo A-I. Alkaline treatment of freshly prepared sera, HDL, or apo HDL with sodium hydroxide simulated the effect of storage, allowing this material to react strongly with MAB 3D4, 6B8. As expected, there was a decrease in the reactivity of MAB 5F6 with alkali-treated fresh material compared to untreated fresh material. However, further investigation showed that alkaline treatment does not completely mimic the effect of storage. MAB 2F1, which reacts poorly with fresh material, reacted very poorly with alkali-treated fresh material, and MAB 3G10 and 4F7, which react well with fresh material, reacted even better with alkali-treated fresh material. While isoelectric focusing of apo HDL prepared from stored serum showed a redistribution of apo A-I toward more acidic isoforms compared to fresh serum, alkaline treatment of apo HDL resulted in partial cleavage of apo A-I and in the generation of isoforms more acidic than known apo A-I isomorphs. Therefore, alkaline treatment of serum is only a partial model for antigenic modification of apo A-I upon storage. These results demonstrate that in vitro conditions (storage or alkaline treatment) selectively modify certain antigenic sites of apo A-I, but not others. This phenomenon, which is probably related to deamidation, may affect apo A-I immunoassays with either monoclonal or polyclonal antibodies. PMID- 3085647 TI - Chronic lead nephropathy in Queensland: alternative methods of diagnosis. AB - Indices of past lead absorption were measured and compared in patients with chronic renal failure from many causes, including some with chronic lead nephropathy. X-ray fluorescence (XRF) yielded finger bone lead concentrations by a new in vivo method. These correlated significantly with excess urinary lead following calcium di-sodium EDTA (ethylenediamine tetra-acetate) and erythrocyte lead concentration. Discriminant function analysis demonstrated that the patients in the study could be separated into two groups without any reference to the EDTA lead excretion test using the following variables, all of which contributed significantly to the discrimination. In order of importance, these were: a childhood history of acute lead poisoning, a history of gout, a family history of gout and detectable XRF finger bone lead. Although the XRF finger bone lead measurement is convenient and non-invasive, its lack of sensitivity (48%) limits its usefulness as a screening test for chronic lead nephropathy. PMID- 3085648 TI - Hepatitis and neutropenia secondary to gold thiomalate therapy for rheumatoid arthritis. AB - A 37 year old female with rheumatoid arthritis developed clinical and biochemical evidence of hepatitis after receiving 80 mg of sodium aurothiomalate. Inadvertent rechallenge with sodium aurothiomalate led to recurrence of the biochemical abnormalities and a profound neutropenia and eosinophilia. PMID- 3085649 TI - Molecular approaches to vaccines. PMID- 3085650 TI - Amino acid catabolism by perfused rat hindquarter. The metabolic fates of valine. AB - Hindquarters from starved rats were perfused with plasma concentrations of amino acids, but without other added substrates. Release of amino acids was similar to that previously reported, but, if total amino acid changes were recorded, alanine and glutamine were not formed in excess of their occurrence in muscle proteins. In protein balance (excess insulin) there was no net formation of either alanine or glutamine, even though the branched-chain amino acids and methionine were consumed. If [U-14C]valine was present, radiolabelled 3-hydroxyisobutyrate and, to a lesser extent, 2-oxo-3-methylbutyrate accumulated and radiolabel was incorporated into citrate-cycle intermediates and metabolites closely associated with the citrate cycle (glutamine and glutamate, and, to a smaller extent, lactate and alanine). If a 2-chloro-4-methylvalerate was present to stimulate the branched-chain oxo acid dehydrogenase, flux through this step was accelerated, resulting in increased accumulation of 3-hydroxyisobutyrate, decreased accumulation of 2-oxo-3-methylbutyrate, and markedly increased incorporation of radiolabel (specific and total) into all measured metabolites formed after 3 hydroxyisobutyrate. It is concluded that: amino acid catabolism by skeletal muscle is confined to degradation of the branched-chain amino acids, methionine and those that are interconvertible with the citrate cycle; amino acid catabolism is relatively minor in supplying carbon for net synthesis of alanine and glutamine; and partial degradation products of the branched-chain amino acids are quantitatively significant substrates released from muscle for hepatic gluconeogenesis. For valine, 3-hydroxyisobutyrate appears to be quantitatively the most important intermediate released from muscle. A side path for inter-organ disposition of the branched-chain amino acids is proposed. PMID- 3085651 TI - Arachidonate mobilization in diacyl, alkylacyl and alkenylacyl phospholipids on stimulation of rat platelets by thrombin and the Ca2+ ionophore A23187. AB - Platelet stimulation by thrombin or Ca2+ ionophore induces mobilization of arachidonate from lipid stores. We have previously shown that, in [14C]arachidonic acid-prelabelled resting platelets, [14C]arachidonate was transferred from diacyl-sn-glycerophosphocholine to ethanolamine and choline containing ether phospholipids. This transfer reached an equilibrium after 5 h incubation [Colard, Breton & Bereziat (1984a) Biochem. J. 222, 657-662]. [14C]Arachidonate-prelabelled platelets having reached this transfer equilibrium were used to study the mobilization of arachidonate in etheracyl and diacyl phospholipids. Upon thrombin stimulation, arachidonate decreased in diacyl-sn glycero-3-phosphoinositol, in alkylacyl- and diacyl-sn-glycero-3-phosphocholine and increased in alkenylacyl- and diacyl-sn-glycero-3-phosphoethanolamine. Upon challenge with Ca2+ ionophore A23187, arachidonate decreased in diacyl-sn-glycero 3-phosphoethanolamine, in diacyl- and alkylacyl-sn-glycero-3-phosphocholine and increased in alkenylacyl-sn-glycero-3-phosphoethanolamine. We also compared arachidonate mobilization in platelets stimulated immediately after [14C]arachidonic acid chase with platelets stimulated after 5 h reincubation. We observed that the arachidonate newly incorporated into diacyl-sn-glycero-3 phosphocholine and triacylglycerols was rapidly released upon stimulation. This suggests the presence in these two lipids of a rapidly-turning-over arachidonate pool. PMID- 3085652 TI - Properties of baby-hamster kidney (BHK) cells treated with Swainsonine, an inhibitor of glycoprotein processing. Comparison with ricin-resistant BHK-cell mutants. AB - Baby-hamster kidney (BHK) cells were grown continuously in long-term monolayer culture in the presence of Swainsonine, an inhibitor of alpha-mannosidase II, a processing enzyme involved in glycoprotein biosynthesis. The asparagine-linked oligosaccharides (N-glycans) were isolated from Pronase-digested cells by gel filtration, ion-exchange chromatography and affinity chromatography on concanavalin A--Sepharose and lentil lectin--Sepharose. The major N-glycans, analysed by 500 MHz 1H-n.m.r. spectroscopy, were identified as hybrid structures containing five mannose residues and neutral high-mannose N-glycans. The major hybrid species contained a core-substituted fucose alpha(1----6) residue and a NeuNAc alpha(2----3)Gal beta(1----4)GlcNAc terminal sequence; smaller amounts of non-sialylated and non-fucosylated hybrid structures were also detected. Swainsonine-treated cells also produced neutral oligosaccharides containing a single reducing N-acetylglucosamine residue substituted with polymannose sequences. The glycopeptide composition of Swainsonine-treated BHK cells resembles closely that of the ricin-resistant BHK cell mutant, RicR21 [P. A. Gleeson, J. Feeney and R. C. Hughes (1985) Biochemistry 24, 493-503], except the hybrid structures of RicR21 cells contain three, not five, mannose residues. Like RicR21 cells, Swainsonine-treated BHK cells showed a greatly increased resistance to ricin cytotoxicity, but not to modeccin, another galactose-binding lectin. These effects were readily reversed on removal of Swainsonine and growth in normal medium. PMID- 3085653 TI - Resolution of branched-chain oxo acid dehydrogenase complex of Pseudomonas aeruginosa PAO. AB - Branched-chain oxo acid dehydrogenase was purified from Pseudomonas aeruginosa strain PAO with the objective of resolving the complex into its subunits. The purified complex consisted of four proteins, of Mr 36,000, 42,000, 49,000 and 50,000. The complex was resolved by heat treatment into the 49,000 and 50,000-Mr proteins, which were separated by chromatography on DEAE-Sepharose. The 49,000-Mr protein was identified as the E2 subunit by its ability to catalyse transacylation with a variety of substrates, with dihydrolipoamide as the acceptor. P. aeruginosa, like P. putida, produces two lipoamide dehydrogenases. One, the 50,000-Mr protein, was identified as the specific E3 subunit of branched chain oxo acid dehydrogenase and had many properties in common with the lipoamide dehydrogenase LPD-val of P. putida. The second lipoamide dehydrogenase had Mr 54,000 and corresponded to the lipoamide dehydrogenase LPD-glc of P. putida. Fragments of C-terminal CNBr peptides of LPD-val from P. putida and P. aeruginosa corresponded closely, with only two amino acid differences over 31 amino acids. A corresponding fragment at the C-terminal end of lipoamide dehydrogenase from Escherichia coli also showed extensive homology. All three peptides had a common segment of eight amino acids, with the sequence TIHAHPTL. This homology was not evident in any other flavoproteins in the Dayhoff data base which suggests that this sequence might be characteristic of lipoamide dehydrogenase. PMID- 3085654 TI - Hydroxyl-radical production and ethanol oxidation by liver microsomes isolated from ethanol-treated rats. AB - In order to distinguish between the mechanism of microsomal ethanol oxidation and hydroxyl-radical formation, the rate of cytochrome P-450 (P-450)-dependent oxidation of dimethyl sulphoxide (Me2SO) was determined in the presence and in the absence of iron-chelating compounds, in liver microsomes from control, ethanol- and phenobarbital-treated rats. Ethanol treatment resulted in a specific increase (3-fold) of the microsomal ethanol oxidation and NADPH consumption per nmol of P-450. A form of P-450 was purified to apparent homogeneity from the ethanol-treated rats and characterized with respect of amino acid composition and N-terminal amino acid sequence. Specific ethanol induction of a cytochrome P-450 species having a catalytic-centre activity of 20/min for ethanol and consuming 30 nmol of NADPH/min could account for the results observed with microsomes. Phenobarbital treatment caused 50% decrease in the rate of ethanol oxidation and NADPH oxidation per nmol of P-450. The rate of oxidation of the hydroxyl-radical scavenger Me2SO was increased 3-fold by ethanol or phenobarbital treatment when expressed on a per-mg-of-microsomal-protein basis, but the rate of Me2SO oxidation expressed on a per-nmol-of-P-450 basis was unchanged. Addition of iron chelating agents to the three different types of microsomal preparations caused an 'uncoupling' of the electron-transport chain accompanied by a 4-fold increase of the rate of Me2SO oxidation. It is concluded that ethanol treatment results in the induction of P-450 forms specifically effective in ethanol oxidation and NADPH oxidation, but not in hydroxyl-radical production, as detected by the oxidation of Me2SO. PMID- 3085655 TI - Isolation and characterization of multiple forms of rat liver UDP-glucuronate glucuronosyltransferase. AB - UDP-glucuronosyltransferase (EC 2.4.1.17) activity was solubilized from male Wistar rat liver microsomal fraction in Emulgen 911, and six fractions with the transferase activity were separated by chromatofocusing on PBE 94 (pH 9.4 to 6.0). Fraction I was further separated into Isoforms Ia, Ib and Ic by affinity chromatography on UDP-hexanolamine-Sepharose 4B. UDP-glucuronosyltransferase in Fraction III was further purified by rechromatofocusing (pH 8.7 to 7.5). UDP glucuronosyltransferases in Fractions IV and V were purified by UDP-hexanolamine Sepharose chromatography. The transferase isoforms in Fractions II, III, IV and V were finally purified by h.p.l.c. on a TSK G 3000 SW column. Purified UDP glucuronosyltransferase Isoforms Ia (Mr 51,000), Ib (Mr 52,000), Ic (Mr 56,000), II (Mr 52,000), IV (Mr 53,000) and V (Mr 53,000) revealed single Coomassie Blue stained bands on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Isoform III enzyme showed two bands of Mr 52,000 and 53,000. Comparison of the amino acid compositions by the method of Cornish-Bowden [(1980) Anal. Biochem. 105, 233-238] suggested that all UDP-glucuronosyltransferase isoforms are structurally related. Reverse-phase h.p.l.c. of tryptic peptides of individual isoforms revealed distinct 'maps', indicating differences in primary protein structure. The two bands of Isoform III revealed distinct electrophoretic peptide maps after limited enzymic proteolysis. After reconstitution with phosphatidylcholine liposomes, the purified isoforms exhibited distinct but overlapping substrate specificities. Isoform V was specific for bilirubin glucuronidation, which was not inhibited by other aglycone substrates. Each isoform, except Ia, was identified as a glycoprotein by periodic acid/Schiff staining. PMID- 3085656 TI - Response of tissue diamine oxidase activity to polyamine administration. AB - The administration to rats of putrescine (750 mumol/kg body wt.) caused in liver, kidney and heart an increase in putrescine at 1 h and in diamine oxidase (EC 1.4.3.6) activity within 3-6 h. An increase in spermidine was observed at 9 h in liver and at 6 h in kidney, whereas in heart there was no change. The increase in diamine oxidase activity by exogenous putrescine was prevented by the administration of actinomycin D and cycloheximide, suggesting that syntheses of mRNA and protein are involved. Equimolar doses of 1,3-diaminopropane, 1,5 diaminopentane and monoacetylputrescine stimulated, similarly to putrescine, hepatic, renal and cardiac diamine oxidase activity. After the injection of a non toxic dose of spermidine (750 mumol/kg body wt.), the increase in diamine oxidase activity occurred at 9 h in all the tissues studied, when a substantial putrescine formation from spermidine occurred. sym-Norspermidine, which is unable to form putrescine, did not cause an increase in enzyme activity. The possibility that the tissue contents of putrescine might regulate diamine oxidase activity is discussed. PMID- 3085657 TI - Genetic deficiency of androsterone UDP-glucuronosyltransferase activity in Wistar rats is due to the loss of enzyme protein. AB - Hepatic microsomal UDP-glucuronosyltransferases towards androsterone and testosterone were purified by chromatofocusing and UDP-hexanolamine affinity chromatography in Wistar rats which had genetic deficiency of androsterone UDP glucuronosyltransferase activity. In rats with the high-activity phenotype, androsterone (the 3-hydroxy androgen) UDP-glucuronosyltransferase was eluted at about pH 7.4 and had a subunit Mr of 52 000, whereas testosterone (the 17-hydroxy steroid) UDP-glucuronosyltransferase was eluted at about pH 8.4 and had a subunit Mr of 50 000. The transferase that conjugates both androsterone and testosterone was eluted at about pH 8.0, had subunit Mr values of 50 000 and 52 000, and appeared to be an aggregate or hybrid of androsterone and testosterone UDP glucuronosyltransferases. In rats with the low-activity phenotype, androsterone UDP-glucuronosyltransferase was absent, whereas testosterone UDP glucuronosyltransferase was eluted at around pH 8.5, with a subunit Mr of 50 000. PMID- 3085659 TI - The effect of hypoxia on the activity of purine nucleoside phosphorylase in rats. AB - The activity of purine nucleoside phosphorylase (PNP) in rat erythrocytes fractionated by centrifugation in microhematocrit capillaries was studied. After seven-day hypoxia (54 kPa) the PNP activity was increased by 67 +/- 4% (S.E.M.) in the lightest fraction of erythrocytes; on the fifth day after hypoxia PNP activity did not differ from control values. PMID- 3085658 TI - Glycoprotein metabolism in normal and beta-mannosidase-deficient cultured goat skin fibroblasts. AB - Cultured skin fibroblasts established from goats affected with beta-mannosidosis, an inherited neurovisceral storage disorder, showed an absence of lysosomal beta mannosidase activity and the corresponding accumulation of a trisaccharide (TS) with the structure Man beta (1----4)GlcNAc beta (1----4)GlcNAc (0.4 mumol/g) and lesser amounts (0.15 mumol/g) of a Man beta (1----4)GlcNAc disaccharide (DS). By using purified storage TS isolated from fibroblasts metabolically labelled with [3H]GlcN, no conversion of TS into DS could be demonstrated in homogenates of affected cells at either lysosomal pH (4.4) or cytosolic pH (6.1), or in the culture medium (pH 7.0) of affected cells. Both TS and DS were secreted into the culture medium by affected fibroblasts. When affected fibroblasts were treated with tunicamycin before labelling with [3H]GlcN, the accumulation of both labelled TS and DS was completely inhibited. Treatment of both affected and normal goat fibroblasts with swainsonine resulted in the inhibition of lysosomal alpha-mannosidase activity and in the accumulation of the same labelled oligosaccharides in both. The major storage pentasaccharide from both normal and affected swainsonine-treated fibroblasts was sensitive to digestion with alpha mannosidase and endo-beta-N-acetylhexosaminidase D, suggesting a branched mannose structure and a chitobiose core. In the absence of evidence for the existence of unusual N-linked glycoprotein-associated chitotriose oligosaccharide structures in affected goat fibroblasts, it must be concluded that degradative pathways for N-linked oligosaccharides are similar in both normal and affected goat fibroblasts, and that these pathways differ from catabolic pathways in human fibroblasts. PMID- 3085660 TI - Isolation and some properties of zinc-containing proteins from human placenta. AB - Applying molecular filtration, the presence of two zinc-binding protein fractions in the human placenta was found. Their molecular weights were 47000 and 7900, respectively. A method for isolation of the high-molecular weight fraction from the placenta was elaborated. It consisted in the fractionation with acetone, Sephadex G-75 filtration, DEAE-Sephadex A-25 chromatography and preparative electrophoresis in polyacrylamide gel. It was calculated that 3.93 g-atoms of Zn are bound to one molecule of the protein. Rabbit antibodies against the zinc containing protein formed an immunoprecipitate with the whole human amniotic fluid and with two protein fractions obtained following filtration of the amniotic fluids on Bio-Gel P-2. PMID- 3085661 TI - B and T lymphocyte mitogenic properties in a snake venom. AB - From the crude snake venom of Agkistrodon rhodostoma two mitogenic principles could be detected: A potent T-lymphocyte stimulating anti-beta-D-galactose specific lectin with a molecular mass of about 18 kD and a very strong B lymphocyte mitogenic factor. Whereas the lectin could be purified by affinity chromatography and characterized as a cell agglutinating, but not precipitating lectin, the highly active B-lymphocyte mitogen could be separated but not characterized. Both factors are much stronger than the mitogens known so far. PMID- 3085662 TI - [In vitro and in vivo effect of gold thioglucose on the insulin- and glucagon secretion of the isolated perfused rat pancreas]. AB - Effects of gold thioglucose on the insulin and glucagon secretion by the isolated perfused pancreas of Wistar rats in vivo and in vitro Gold thioglucose (GTG), hitherto administered predominantly to mice can also be used in rats in a non toxic dosage, if GTG is injected intravenously (i.v.) together with sodium hexobarbital. Wistar rats tolerate a single injection of GTG in doses ranging from 40 to 1200 mg/kg bw. GTG (10 mmol/l in the perfusion medium) has no in vitro effect--tested by the isolated perfused rat pancreas--on the basal (5.5 mmol/l glucose) or stimulated (11 mmol/l glucose) insulin (IRI)-secretion. This is valid also for glucagon (IRG)-secretion. After in vivo injection of GTG (600 mg/kg bw, together with sodium hexobarbital (10 mg/100 g bw, i.v.] extensive alterations of IRI- and IRG-secretion result as tested under in vitro conditions in the isolated perfused pancreas of the rat, Glucose stimulation (11 mmol/l) causes a hyperinsulinism and a hypersecretion of IRG, a so-called paradoxical glucagon secretion, lasting for 2 days while IRI secretion is already diminished. At the same time food intake is very low and the body weight decreases. Ten days later the body weight has reached the starting value again and the IRI secretion shows again signs of hyperinsulinism. Six months after a single injection of GTG (600 mg/kg bw, i.v.) the rats were obese and react after glucose stimulation with hyperinsulinism and again with a paradoxical glucagon secretion. The blood glucose levels were normoglycaemic, whereas serum IRI rose in parallel with development of the obesity. Also with histological methods we could distinguish an acute from a chronic phase of GTG toxicity visible in the tested organs (liver, kidney, thyroid gland). The endocrine pancreas reacts after a single injection of GTG with a lowered number of B cells. The remaining cells reveal variable amounts of degranulation. In the early phase the hypothalamus, in particular the ventromedial hypothalamic nucleus, shows most clearly signs of destruction and 6 months after a single injection of GTG the number of cells is still reduced in this region. We conclude that GTG reacts primarily on the hypothalamus and modulates the reactivity of the endocrine pancreas in a permanent manner via the vegetative nervous system, because we test the function of the pancreas in an in vitro system. As a consequence the threshold of the B and A cell against the stimulus glucose is altered in two ways.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3085663 TI - Messenger RNA for a phorbol-ester induced 48,000 dalton protein from human melanoma cells. AB - Messenger RNA of the phorbol ester-induced 48kDa protein from human melanoma cells (Bowes) was isolated, characterized and used to study the protein processing. The 48kDa mRNA is induced simultaneously with that of tissue-type plasminogen activator. This induction is prominent as shown by sedimentation profiles on linear sucrose gradients. The mRNA can be isolated by classical phenol extractions, has a poly(A)-tail and sediments with a coefficient of 20 S. Translation in reticulocyte lysates yields a 48kDa protein whether the translation is modified with canine pancreas microsomal membranes or not. Analysis of 48kDa mRNA translation products by sodium dodecyl sulphate/polyacrylamide gel electrophoresis showed that the phorbol ester-induced 48kDa is a monomeric one-chain polypeptide. Glycosylation could not be detected, nor signal peptide cleaving, suggesting that it is a non-secreted intracellular protein. PMID- 3085664 TI - Dexamethasone inhibits antitumor potential of activated macrophages by a receptor mediated action. AB - The capacity to inhibit P815 mastocytoma growth was induced in macrophages elicited by trehalose dimycolate by a short in vitro treatment with 10 ng/ml LPS. Activation by LPS was associated with a 3 fold increase in the rate of glucose consumption by macrophages. Incubation of activated macrophages with the glucocorticoid dexamethasone (greater than or equal to 10(-8) M) for several hours (greater than or equal to 5 h) resulted in an inhibition of antitumoral activity and a decrease of glucose consumption. Hydrogen peroxide production is a property expressed by trehalose dimycolate-elicited macrophages independently of the presence of LPS. The capacity to release hydrogen peroxide upon triggering was not affected by a pretreatment of macrophages by dexamethasone. The antiglucocorticoid compound RU 38486, known to bind with a high affinity to glucocorticoid receptors without agonist effect, prevented the inhibitory actions of dexamethasone, indicating that these are receptor-mediated. PMID- 3085665 TI - Phorbol esters stimulate phosphate accumulation synergistically with A23187 in cultured renal tubular cells. AB - The effects of phorbol esters and diacylglycerol on phosphate accumulation in the cultured mouse kidney cells were investigated to assess the possible role of Ca2+ activated, phospholipid dependent protein kinase (protein kinase C) on the renal phosphate handling. 12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulated phosphate accumulation dose-dependently. TPA-induced phosphate accumulation was synergistically enhanced with A23187. 4 alpha-phorbol 12,13-didecanoate did not stimulate the phosphate accumulation, while 4 beta-phorbol 12,13-didecanoate stimulated it. Additionally, 1-oleoyl-2-acetyl-glycerol exhibited a stimulatory effect on phosphate accumulation. These data indicated that protein kinase C is one of possible regulators of phosphate transport at the renal tubules. PMID- 3085666 TI - Differential mechanisms of translocation of protein kinase C to plasma membranes in activated human neutrophils. AB - Three classes of activators of human neutrophils that induce the intracellular translocation of protein kinase C from the cytosol to the particulate fraction were compared for their effects on the properties of the particulate (membrane bound) enzyme. In cells stimulated with 10 ng/ml of phorbol-12-myristate-13 acetate (PMA) the particulate enzyme is almost fully active in the absence of added Ca2+ or phospholipids and this activity is not released by the Ca2+ chelator EDTA. In contrast, binding of protein kinase C to the particulate fraction in cells treated with the chemotactic factor f-Met-Leu-Phe (fMLF) or with the ionophore A-23187 plus Ca2+ is observed only when the cells are lysed in the presence of 1 mM Ca2+. With these stimuli the particulate enzyme retains a nearly absolute requirement for Ca2+ and phospholipids. Thus only the full intercalation of protein kinase C caused by PMA, which is resistant to removal by chelators stabilizes an active form of protein kinase C in the neutrophil membrane. In confirmation of this conclusion, in isolated plasma membranes loaded with partially purified protein kinase C by incubation with 5 microM Ca2+ further incubation with PMA, but not with fMLF, caused a significant fraction of the bound PKC to become resistant to removal by chelators, and to be nearly fully active in the absence of added activators. PMID- 3085667 TI - Bicarbonate exchange kinetics at equilibrium across the erythrocyte membrane by 13C NMR. AB - The rate of exchange of 13C-labelled bicarbonate across the membranes of human erythrocytes in suspension, at thermal and chemical equilibrium, was measured using 13C NMR spectroscopy: the permeability coefficient (3.34 X 10(-4) cm s-1) agrees well with previous values obtained with other methods. Data analysis was complicated by the need to consider the Donnan ratio of the charged species inside and outside the cells. This work appears to be the first, involving the present NMR procedure, for studying fast membrane transport of a molecule other than water. PMID- 3085668 TI - Activation of protein kinase C inhibits sodium fluoride-induced elevation of human platelet cytosolic free calcium and thromboxane B2 generation. AB - Addition of NaF to washed platelets produces a dose-dependent and transient elevation of the intracellular free calcium concentration ([Ca++]i), thromboxane B2 (TxB2) generation and dense granule release, all of which are significantly inhibited when the extracellular calcium concentration ([Ca++]e) is reduced with EGTA. Inhibition of platelet cyclo-oxygenase by acetylsalicylic acid (ASA) does not affect NaF-induced elevation of [Ca++]i and dense granule release in the presence of 1 mM [Ca++]e. Pre-incubation of the platelets with the phorbol ester TPA produces a marked inhibition of NaF-induced elevation of [Ca++]i and TxB2 generation without affecting dense granule release. Thus, NaF may have more than one site of action. Pretreatment of the platelets with the selective protein kinase C inhibitor H7 prevents TPA induced inhibition of NaF mediated rise in [Ca++]i and TxB2 generation. Thus we propose that NaF induced calcium mobilisation is analogous to receptor-operated calcium mobilisation in platelets, as it is readily inhibited by protein kinase C activation or by the reduction of [Ca++]e and is independent of platelet cyclo-oxygenase activity. PMID- 3085669 TI - Selective labeling of functional groups on membrane proteins or glycoproteins using reactive biotin derivatives and 125I-streptavidin. AB - Amino groups, sulfhydryl groups or oxidation-induced aldehydes on erythrocyte membrane proteins and/or glycoproteins, were reacted with biotinyl N hydroxysuccinimide ester (BNHS), 3-(N-maleimido-propionyl) biocytin (MPB) or biocytin hydrazide (BCHZ), respectively. The detergent-lysed biotinylated samples were subjected to SDS-polyacrylamide gel electrophoresis, and the proteins were transferred onto nitrocellulose membranes. The blot was then incubated with a solution containing 125I-streptavidin, and processed for autoradiography. The advantages of this approach over previously reported procedures for labeling the three functional groups include the following: extremely high sensitivity; short exposure times of autoradiograms and relatively low levels of radioactivity; single-step radiolabeling procedures subsequent to processing and handling of gels and no background labeling in control samples. PMID- 3085670 TI - Tetrahydromethanopterin methyltransferase, a component of the methane synthesizing complex of Methanobacterium thermoautotrophicum. AB - A new enzyme, tetrahydromethanopterin methyltransferase, which catalyzes the transfer of methyl groups from methyl-tetrahydromethanopterin to 2-mercaptoethane sulfonate, has been found in the methane synthesizing complex of Methanobacterium thermoautotrophicum. The enzyme is oxygen sensitive and has a well defined pH optimum at pH 6.7. There was no methyl group transfer when the enzyme was heated to 100 degrees for 5 min. The product of the forward reaction, methyl-CoM, was positively identified by TLC and high voltage paper electrophoresis. The demethylation of methyl-CoM, in the absence of methane synthesis, was dependent on the addition of H4MPT which suggests that the enzyme reaction is reversible. PMID- 3085671 TI - Prostaglandin release by the chick embryo heart is increased by 2,3,7,8 tetrachlorodibenzo-p-dioxin and by other cytochrome P-448 inducers. AB - Exposure of chick embryos in ovo to cytochrome P-448 inducers 2,3,7,8 tetrachlorodibenzo-p-dioxin, 3,4,3',4'-tetrachlorobiphenyl, 3,4,5,3',4',5' hexachlorobiphenyl and beta-napthoflavone, increased cardiac prostaglandins in vitro. The dose response relationships were biphasic with prostaglandin release increasing at the low doses and returning to basal levels at higher doses. Phenobarbital was ineffective. Increased cardiac prostaglandin release was detected at doses that induced hepatic 7-ethoxyresorufin deethylase (7-ER) but which were below the threshold for cardiac induction. The fall in prostaglandin release coincided with induction of cardiac 7-ER and therefore may be attributable to increased prostaglandin metabolism. These studies show that the P 450 system may interact with the arachidonic acid metabolizing system to increase PG release and that this effect may be part of the pleiotypic response to Ah receptor activation. PMID- 3085673 TI - Amyloid kidney stones of uremic patients consist of beta 2-microglobulin fragments. AB - Urinary stones with amyloid structure, obtained from uremic patients, were analyzed according to molecular weight, amino acid sequence, and antigenic content. A major protein of approximately 7 kD, designated AB protein, was isolated by size exclusion using HPLC in 60% formic acid. AB protein reacted in immunodiffusion only with an antiserum to beta 2-microglobulin, with beta 2m spurring over AB protein. N-terminal amino acid sequence analysis defined two fragments homologous to beta 2m. One fragment commenced with Ile at position 7 and the other with Ser at position 20, with a cleavage point subsequent to a lysyl residue in both. It is concluded that beta 2m is a precursor of urinary amyloid stones and intratubular concretions of patients with preterminal and terminal renal failure; limited proteolysis is involved in AB amyloid generation. PMID- 3085672 TI - Release of a lectin from a fatty acid auxotroph of Saccharomyces cerevisiae grown in presence of oleic acid. AB - The unsaturated fatty acid-requiring mutant KD 115 of Saccharomyces cerevisiae secretes a lectin when grown in presence of oleic acid. This lectin is homogeneous on PAGE at pH 8.3, has an approximate molecular weight of 320,000, pI of 4.2 and contains about 60% sugar. It agglutinates chicken and different mammalian erythrocytes, but lyses rabbit red cells only. It is D-galactose specific. To our knowledge, this is the first report of a hemagglutinin from yeast. PMID- 3085674 TI - Enrichment and characterization of angiotensin II using affinity and high pressure liquid chromatography. Part I. Affinity purification and characterization of Ang II antiserum. PMID- 3085675 TI - In vitro translation products of Drosophila mitochondria are contaminated with newly synthesized bacterial proteins. AB - A previous study reported in this journal suggested that in vitro synthesis of Drosophila mitochondrial polypeptides could be performed provided certain bacterial growth inhibitors were employed in the medium (Alziari, S., Stepien, G., and Durand, R. (1981) Biochem. Biophys. Res. Comm. 99, 1-8). We report here that despite the absence of microbial proliferation, bacteria isolated from adult Drosophila synthesize a significant number of proteins in such a medium. Thus, considerable caution must be exercised in the interpretation of studies utilizing this medium which claim to provide data on the translation products of isolated mitochondria from adult insects. PMID- 3085676 TI - Genetics of xenobiotic metabolism in Drosophila. I. Genetic and environmental factors affecting glutathione-S-transferase in larvae. AB - The enzyme glutathione-S-transferase, which plays a crucial role in xenobiotic detoxification, was investigated in Drosophila melanogaster. Based upon examination of substrate specificities and pH optima, it was observed that the enzyme in Drosophila is considerably more restricted in its activities than in mammals. The effects of various xenobiotics on activities in third instar larvae were examined. While beta-naphthoflavone and phenobarbital had no effect, pentamethyl benzene (PMB) administration resulted in a 50% increase in enzyme activity. Comparison of lines of known genetic composition indicates that the degree of response to PMB is modulated by genes on chromosome II, and that differences exist with respect to the patterns of response of activities towards the substrates 1-chloro-2, 4-dinitrobenzene and ethacrynic acid. Results obtained suggest the existence of at least two loci on chromosome II that code for glutathione S-transferase isozymes. PMID- 3085677 TI - Changes in hepatic drug metabolism in alloxan-diabetic male rabbits. PMID- 3085678 TI - Effect of 6-hydroxydopamine on polymerization of tubulin. Protection by superoxide dismutase, catalase, or anaerobic conditions. AB - Microtubular protein (tubulin) isolated from porcine brain was subjected to selected oxidative stresses, including incubation with the neurotoxin 6 hydroxydopamine (6-OHDA) under aerobic and anaerobic conditions. The functional capacity of the tubulin was determined on the basis of its ability to form microtubules as measured by alterations in the viscosity of the test mixtures, and confirmed by electron microscopy. 6-OHDA completely inhibited formation of microtubules at concentrations as low as 10 mM. Assembled microtubules were half as susceptible to destruction by 6-OHDA as unaggregated tubulin. Anaerobic conditions or the presence of catalase, superoxide dismutase, or a mixture of superoxide dismutase and catalase provided partial protection against 6-OHDA induced destruction. In control reactions, tubulin-containing solutions incubated for up to 8 hr at ambient oxygen tensions, also showed significant decreases in ability to polymerize. Anaerobic conditions provided partial protection against this loss of function. In contrast, ascorbate accelerated the loss of activity upon standing, while glutathione or dithiothreitol offered no protection. PMID- 3085679 TI - Induction of UDP-glucuronyltransferase and arylhydrocarbon hydroxylase activity in mouse skin and in normal and transformed skin cells in culture. AB - Methods have been developed which allow quantitative determination of UDP glucuronyltransferase (UDPGT) and arylhydrocarbon hydroxylase (AHH) activities in unfractionated mouse skin. These methods were used for comparative studies of basal and induced enzyme activities in whole skin and cultured skin cells. After topical application of Aroclor 1254 to the skin UDPGT activities towards 1 naphthol, 3-hydroxybenzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol were increased 3-fold and AHH activity was increased 15-fold. Topical application of the inducer also led to a marked increase of these enzyme activities in liver. UDPGT activity towards 1-naphthol was comparable in whole skin and in cultured keratinocytes and fibroblasts. In contrast, AHH activity was higher in cultured keratinocytes than in skin. In transformed epithelial cell lines the pattern of drug metabolizing enzymes was altered: UDPGT activity was increased 4- to 6-fold whereas AHH activity was decreased. However, AHH activity was still inducible by benz[a]anthracene or 7,12-dimethylbenz[a]anthracene in cultured cells. The altered pattern of AHH and UDPGT in transformed epithelial cell lines is consistent with toxin-resistance of initiated cells, similar to the toxin resistance phenotype characterized in liver after initiation of hepatocarcinogenesis. PMID- 3085680 TI - Evidence for the metabolism of mitozantrone by microsomal glutathione transferases and 3-methylcholanthrene-inducible glucuronosyl transferases. AB - The metabolism of mitozantrone, a chemotherapeutic agent used in the treatment of breast cancer, has been studied in vitro using rat liver subcellular fractions. This compound would appear to be metabolized by two interesting pathways. One involves conjugation with glucuronic acid, catalyzed most effectively by a 3 methylcholanthrene-inducible glucuronosyl transferase. The other pathway appears to be a glutathione conjugation reaction which requires prior metabolism by cytochrome P-450. The reaction with glutathione appears to be enzymatic as 1 chloro-2,4-dinitrobenzene was a potent inhibitor of this reaction. Liver cytosol did not enhance the microsomal rate of glutathione-conjugate formation, suggesting an important role for the microsomal glutathione transferases in the disposition of this compound. The relationship between these reactions and the mode of action of mitozantrone is discussed. PMID- 3085681 TI - Inhibition of diamine oxidase and S-adenosylmethionine decarboxylase by diminacene aceturate (berenil). PMID- 3085682 TI - Effects of ethanol and secretagogues on the composition of phosphatidylinositol in pancreas and submaxillary gland. PMID- 3085683 TI - Bronchiolitis in a rheumatoid arthritis patient receiving auranofin. AB - A patient with severe rheumatoid arthritis and sicca symptoms was treated with auranofin. During auranofin therapy, she developed irreversible airways obstruction due to bronchiolitis. Whereas this complication could have been due to her underlying disease, we discuss here the possibility of its being related to the auranofin therapy. PMID- 3085684 TI - The fate of [14C]-mesna in the rat. AB - [14C]-Mesna (sodium 2-mercaptoethanesulphonate) has a short serum t1/2 (about 16.5 min) and is excreted in the urine. Within 24 h approx. 77% of the administered dose appeared in the urine. It is bound to serum albumin and immunoglobulins. Total serum protein binding is about 9.7% of the total amount present in serum. [14C]-mesna + [14C]-dimesna (bis[2-mercaptoethane sulphonate]) are present in the blood stream, and so are found in the body organs at low concentration, however, localisation of radioactivity occurs in the kidneys. The binding of [14C]-mesna to proteins and the localisation of [14C]-mesna or [14C] dimesna in the kidneys are discussed in the context of the cell killing efficacy of the oxazaphosphorines. PMID- 3085685 TI - Apoprotein D in a healthy, male population and in male myocardial infarction patients and their male, first-degree relatives. AB - This report examines the correlation of serum apoprotein D with other lipoprotein lipids and apoproteins in a healthy, male population and compares the levels of high density lipoprotein apoprotein D of this control population with 2 samples composed of male, acute myocardial infarction patients and their healthy, male, first-degree relatives. Highly significant correlations were observed with very low density lipoprotein lipids (negative), high density lipoprotein lipids (positive) and serum triglycerides (negative). Serum and low density lipoprotein apoprotein B was not correlated with serum apoprotein D, whereas apoprotein A-I from serum and high density lipoproteins was strongly correlated with apoprotein D. A significant reduction in high density lipoprotein apoprotein D was observed in male, myocardial infarction patients. Their male, first-degree relatives also had lower apoprotein D levels, but the difference was not significant. PMID- 3085686 TI - Platelet formation of 12-hydroxyeicosatetraenoic acid and thromboxane B2 is increased in type IIA hypercholesterolemic subjects. AB - The formation of the major metabolic products of endogenous arachidonic acid (AA) via cyclooxygenase and lipoxygenase pathways in platelets from normal and type IIA hypercholesterolemic subjects was evaluated. 12-Hydroxyeicosatetraenoic acid (12-HETE) and thromboxane B2(TXB2) were determined by selected ion monitoring (SIM) after extraction and purification of collagen stimulated platelet-rich plasma (PRP). The levels of both arachidonic acid metabolites in the non stimulated PRP of control and type IIA subjects were below the detection limit of the method, rising significantly after collagen stimulation. Both 12-HETE and TXB2 levels in collagen-stimulated PRP samples from the patients were significantly higher than levels in controls (P less than 0.001). In view of the key role of 12-HETE in mediating smooth muscle cell migration and proliferation and in stimulating macrophage activity, these data may provide information for the understanding of the elevated incidence of thrombosis and atheromatous lesion in patients with type IIA hypercholesterolemia. PMID- 3085687 TI - Acid-stable low molecular mass proteinase inhibitors in human lung lavage. AB - An acid-stable, low molecular mass proteinase inhibitor, bronchial mucus proteinase inhibitor (BMPI), has been isolated from sputum and partially characterised. A single band with a modal molecular mass of 18 700 was observed following SDS-polyacrylamide gel electrophoresis. BMPI inhibited human leukocyte elastase, cathepsin G, trypsin and chymotrypsin, but not porcine pancreatic elastase. Although BMPI had a molecular mass close to the similarly isolated inhibitor of Girard et al. (Girard, F., Tournier, J.M., Polu, J.M. & Sadoul, P. (1980), Bull. Eur. Physiopathol. Respir. 16 (Suppl.) 237-245), and although it showed immunological cross reactivity to the low molecular mass inhibitor of Kramps et al. (Kramps, J.A., Franken, C., Meyer, C.J.L.M. & Dijkman, J.H. (1981) J. Histochem. Cytochem. 29, 712-719), it was found to have an amino-acid profile different to any previously described inhibitor. BMPI was detectable in bronchoalveolar lavage fluid collected from healthy and diseased human lungs. The median molar ratio of BMPI/alpha 1-proteinase inhibitor (alpha 1 PI) observed in these lavage samples was 0.7, which is generally higher than those derived from the data of other authors. This suggests that BMPI is a different protein to those previously described, although its exact relationship to other low molecular mass proteinase inhibitors remains to be determined. PMID- 3085688 TI - Quinones from archaebacteria, II. Different types of quinones from sulphur dependent archaebacteria. AB - From the sulphur-dependent, anaerobically grown archaebacterium Sulfolobus ambivalens Caldariella quinone, CQ-6(12H) and the new Sulfolobus quinone SQ 6(12H), 6-(3,7,11,15,19,23-hexamethyltetracosyl)-5-methyl-benz[b]thioph en-4, 7 quinone have been isolated as main components. Lower homologues SQ-5-(10H), SQ 4(8H), SQ-3(6H), phylloquinone-like species CQ-6(10H), SQ-6(10H) and the menaquinone MK-6(12H) are present as minor components. The results are compared with those from Sulfolobus acidocaldarius. Thermococcus celer, Desulfurococcus mucosus and Desulfurococcus mobilis do not contain quinones in comparable amounts. PMID- 3085689 TI - The major basic proteins of bull seminal vesicle secretion. AB - We have employed HPLC on reversed phase columns to analyse the major basic proteins from bull seminal vesicle secretion. The identification of proteins was achieved by comparison with authentic protein samples from bull seminal plasma as well as immunological characterisation using antisera directed against the latter proteins. The major basic proteins from bull seminal plasma: bull seminal proteinase inhibitor II (BUSI II), the seminal ribonuclease BS1, the protein P6 as well as the antimicrobial protein were also identified as the main constituents of the fraction of basic proteins derived from seminal vesicle secretion. FPLC using Mono S HR columns was also found to resolve the mixture of basic proteins and proved to be especially useful with respect to the isolation of the antimicrobial protein from basic proteins of seminal vesicle secretion. The identity of the antimicrobial protein from bull seminal plasma with the respective protein from seminal vesicle secretion was confirmed by amino-acid analysis and comparison of tryptic peptide patterns by HPLC. The antimicrobial protein was isolated from seminal vesicle secretion with a yield of 3 mg/ml of secretion. PMID- 3085690 TI - Sterol manipulation that modulates the alteration in membrane fluidity of Tetrahymena pyriformis during temperature acclimation. AB - Our previous results [Umeki and Nozawa (1983) Biochem. Biophys. Res. Commun. 113, 96-101] suggested that ergosterol-replaced Tetrahymena cells (ergosterol-cells) accomplish an adaptive modification of fatty-acid composition by a preferential increase in palmitoyl-CoA desaturase activity, which is principally due to the increased content of the terminal component (cyanide-sensitive factor) of the desaturase system. The present study was designed to obtain information as to how the membrane fluidity of ergosterol-cells is changed during cold temperature acclimation. The order parameter (S) of liposomes prepared from ergosterol-cell lipids was reduced more rapidly after a temperature shift-down than that of control liposomes prepared from native cells containing tetrahymanol. These results indicate that, unlike native cells containing tetrahymanol, ergosterol cells strive to accomplish cold temperature acclimation by undergoing a great modification of membrane fluidity because of the altered microsomal desaturase activity. PMID- 3085691 TI - [Isovolumic and auxovolumic constants of cardiac relaxation in evaluating its inotropism]. AB - The left ventricular pressure curve was registered in experiments on isolated guinea pig heart performing external work. An analysis of initial diastolic portion of the curve in logarithmic scale has revealed for the first time that the time course of the pressure fall is accelerated during transition from isovolumic to auxovolumic phase. The constant of pressure fall rate in auxovolumic phase (ACPFR) has been approximately 1.5-fold higher than isovolumic constant. The former also changed significantly more than the latter one during elevation in Ca2+ perfusate concentration or EGTA addition. A parallel reduction in ACPFR and rate of left ventricular filling during EGTA addition was observed in special experiments with elimination of left atrium distension. Thus, inotropic changes in myocardial relaxation seem to determine left ventricular filling rate. PMID- 3085692 TI - Regulation of the assembly and expression of variable-region genes. PMID- 3085693 TI - [Prognosis of partial epilepsy in childhood]. PMID- 3085694 TI - [Visual evoked potentials in photosensitive epilepsy--effect of valproic acid therapy]. PMID- 3085695 TI - [The anti-tumor efficacy of lymphokine-activated killer (LAK) cells induced in vitro from peripheral blood lymphocytes of patients with malignant glioma]. AB - We studied whether lymphokine-activated killer (LAK) cells were capable of being induced in vitro from peripheral blood lymphocytes (PBL) of patients with malignant glioma, by using recombinant IL-2 (rIL-2). We then investigated whether they possessed anti-tumor efficacy against malignant gliomas (ONS-12, -20, -44). Human LAK cells were generated by placing 5 X 10(6) PBL into each well of 24-well plates (Corning) containing 2 ml of complete medium (CM) with 10 units of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd.). The CM consisted of RPMI 1640 with 0.1 mM nonessential amino acids, 1 microM sodium pyruvate, 5 X 10(-5) M 2-mercaptoethanol, 50 micrograms/ml gentamicin sulfate, 0.03% glutamine and 1% heat-inactivated human AB serum. The plates were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hours. The LAK cells were then harvested, washed three times with Hanks balanced solution, and resuspended in RPMI 1640 with 1% heat-inactivated human AB serum for the in vitro cytotoxicity assays. The anti-tumor cytotoxic activity of LAK cells was estimated in triplicate by 4-hr 51Cr release assays. The cytotoxic activity of the LAK cells against autogeneic ONS-44 glioma cells and PHA blasts was approximately 30% and a few %, respectively. The Natural Killer (NK) activity of the patient with ONS-44 glioma cells was equivalent to that of healthy subject.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085696 TI - [Lissajous figures of the visual evoked potentials]. AB - The value of the visual evoked potential (VEP) technique for diagnosis of epilepsy is limited. Except for photosensitive epilepsies, the visual evoked potentials (VEPs) do not reveal more than a routine EEG. As one of the reasons of that, it is pointed out that a review of VEP literature reveals different "normal values" for peak latencies and amplitudes. Thus in this study, lissajous figures of VEPs (VEP-L) were attempted instead of the measurement of peak latencies and amplitudes of VEPs. Thirty six epileptic subjects (14 have partial seizures, 22 have generalized seizures) and 22 control subjects were investigated. Several EEGs to storoboscopic flashes were recorded from scalp electrodes placed at the frontal (Fz) and occipital (Oz) regions according to the 10-20 electrode system, using a right ear as nonreference with a EEG amplifier (Nihon Kohden ME-175 E) and a data recorder (TEAC R-60). Then the phasic relationships between the VEPs from the two areas were analyzed with a medical computer (Nohon Kohden ATAC-2300) and printed out as VEP-L. The results are summerized as follows: First, as time passes from 100 msec to 200 msec in the VEP-L, the epileptic patient group showed more right-roted types than that of the control group (p less than 0.01). Second, the VEP-L at the periods from 50 msec after photic stimulus, were classified into 5 types inspectively. The 5 types are the right-ascending type, the left ascending type, the vertical type, the horizontal type, and the circular type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085697 TI - A ventilator for carbon dioxide laser bronchoscopy. AB - A jet ventilator is described. It is designed for use in patients undergoing carbon dioxide laser vaporization of intraluminal tumours, and obstructions in the trachea and main bronchi. The ventilator overcomes two major anaesthetic problems during laser vaporization in the tracheobronchial tree. It ensures adequate alveolar ventilation and it evacuates smoke generated by the laser. The device has two modes of operation, an automatic ventilation mode and a second mode in which ventilation and suction can be alternated--laser ventilation mode. PMID- 3085699 TI - Conference report. The polyol pathway and complications of diabetes. PMID- 3085698 TI - Plasma levels of nitroglycerin generated by three nitroglycerin patch preparations, Nitradisc, Transiderm-Nitro and Nitro-Dur and one ointment formulation, Nitrobid. AB - Twenty-four healthy male subjects participated in a study comparing plasma concentrations of nitroglycerin generated by single applications of Nitradisc 32 mg, Transiderm-Nitro 50 mg and Nitro-Dur 104 mg patches and from one inch of Nitrobid 2% ointment. The three patch preparations are designed to release 10 mg nitroglycerin systemically over a 24 h period. Nitrobid ointment is intended to deliver 15 mg nitroglycerin per inch of ointment, and to be reapplied at least every 8 h. Blood was taken for nitroglycerin assay up to and including 24 h after each application. Assay for nitroglycerin was performed using a gas chromatography-mass spectrometry technique. Plasma concentrations of nitroglycerin were sustained up to the 24 h mark with all three patch preparations, but not with application of Nitrobid ointment. Nitrobid was associated with a rapid rise in nitroglycerin plasma concentrations maximal 1 h after application. Plasma concentrations of nitroglycerin absorbed from Nitrobid ointment fell below those absorbed from all three patch preparations after 8 h. Clinically, all four formulations were similar with respect to side effects, with headache and dizziness being the most common. PMID- 3085700 TI - Fluvoxamine--a baseline study of clinical response, long term tolerance and safety in a general practice population. PMID- 3085702 TI - Lack of correlation between antitumour response and serum interferon levels in mice treated with SSM, an immunotherapeutic anticancer agent. PMID- 3085701 TI - Molecular evidence for the clonal origin of blast crisis in chronic myeloid leukaemia. AB - Cytogenetic and enzymatic studies have shown that chronic myeloid leukemia (CML) represents the clonal proliferation of a pluripotent stem cell. The Philadelphia chromosome (Ph') is the characteristic karyotypic abnormality seen in this disease, although the exact role of this clonal marker in the pathogenesis of CML is uncertain. At a molecular level, the Ph' has recently been shown to represent the translocation of c-abl to a limited (breakpoint cluster region, bcr) on chromosome 22. We have used probes for the bcr gene to obtain molecular evidence for the clonal origin of blast crisis in 2 patient with CML. In both cases, the first with myeloid and the second with lymphoid blast crisis, there was rearrangement of the bcr gene. The patterns of rearrangement varied between patients but were identical when comparing acute and chronic phases within the same individual. As the Ph' translocation is thought to represent a random recombination event these data not only provide further evidence for the clonal origin of blast crisis in CML, but also suggest that in the second patient this translocation event had already occurred at the pluripotent stem cell. PMID- 3085703 TI - Pure red cell aplasia: lymphocyte inhibition of erythropoiesis. AB - The pathogenesis of pure red cell aplasia (PRCA) was studied in a patient who had no evidence of malignancy. In marrow culture, no erythroid colonies (from late erythroid progenitors [CFU-E]) but normal numbers of well-haemoglobinized erythroid bursts (from early erythroid progenitors [BFU-E]) were found, indicating that BFU-E existed in the patient but that their subsequent in vivo differentiation was inhibited. Autologous coculture studies suggested that inhibition was mediated by the patient's ER + lymphocytes. After remission was induced with cyclophosphamide, autologous ER + cells no longer suppressed in vitro erythropoiesis. However, cryopreserved ER + cells, obtained with anaemia, suppressed BFU-E growth from remission marrow. An expanded population of large granular lymphocytes (LGL) with ER +, Fc gamma +, T3+, T8+, HNK-1+, Ia-, M1 -- phenotype and no functional natural killer (NK) cell activity was noted during PRCA that reverted to normal with remission. For this patient, both in vivo and in vitro evidence demonstrates a cellular inhibition of erythropoiesis at the level of differentiation between BFU-E and CFU-E. PMID- 3085704 TI - Abnormalities of von Willebrand factor in myeloproliferative disease: a relationship with bleeding diathesis. AB - We studied factor VIII related properties in 24 patients with increased platelet number. Twenty-one were affected by myeloproliferative disorders (eight had polycythaemia vera, 13 had essential thrombocythaemia) and three had secondary thrombocytosis. Normal levels of VIII:C and VIIIR:Ag were found while a significant (P less than 0.05) decrease of VIIIR:RCOF (43 +/- 13%) related to a lack of larger multimers of VWF (39 +/- 12%) was observed in 57% of patients with myeloproliferative disorders. A normal VWF pattern was found in the three patients with secondary thrombocytosis. The highest incidence of VWF abnormalities occurred in patients with essential thrombocythaemia (70%) in comparison with polycythaemic patients (38%). A significant (P less than 0.03) correlation between platelet count and the values of both VIIIR:RCOF and VWF multimeric pattern was observed only in patients with polycythaemia vera. The lowest levels of VIIIR:RCOF and the greatest loss of larger VWF multimers (less than 30%) were observed in two patients who presented bleeding symptoms at the time of study and a prolonged bleeding time. In addition, the relationship between VWF pattern and bleeding diathesis was supported by the fact that 75% of the patients with VWF abnormalities had bleeding history. PMID- 3085705 TI - Clinical aspects of LHRH analogues in gynaecology: a review. AB - LHRH agonists are synthetic peptide analogues of hypothalamic luteinizing hormone releasing hormone (LHRH) with superior potency and longer duration of gonadotrophin release. Paradoxically, repeated administration causes pituitary desensitization with diminished gonadotrophin and oestradiol secretion. A state of hypogonadotrophic hypogonadism is reversibly induced; plasma oestrogen can be reduced to castrate levels. LHRH agonists reliably induce anovulation but are unlikely to replace existing contraceptive methods in most normal women. By contrast these agents offer, for the first time, the prospect of inducing a reversible pseudomenopause essentially free of side-effects. LHRH analogues promise to have a profound impact upon the management of a diverse range of oestrogen-dependent gynaecological diseases both benign and malignant. In particular, they may shortly become the gynaecological treatment of choice in endometriosis, as well as becoming part of the management of common gynaecological disorders such as dysfunctional uterine bleeding and uterine fibroids. PMID- 3085706 TI - Use of LHRH analogue to obtain reversible castration in a patient with benign metastasizing leiomyoma. AB - The use of superactive LHRH analogue to provide a reversible form of castration is discussed in the context of the management of a patient with benign metastasizing leiomyoma. The aetiology and prognosis of this rare disease are briefly considered. PMID- 3085707 TI - NADPH-cytochrome P-450 oxidoreductase: flavin mononucleotide and flavin adenine dinucleotide domains evolved from different flavoproteins. AB - The FMN-binding domain of NADPH-cytochrome P-450 oxidoreductase, residues 77-228, is homologous with bacterial flavodoxins, while the FAD-binding domain, residues 267-678, shows a high degree of similarity to two FAD-containing proteins, ferredoxin-NADP+ reductase and NADH-cytochrome b5 reductase. Comparison of these proteins to glutathione reductase, a flavoprotein whose three-dimensional structure is known, has permitted tentative identification of FAD- and cofactor binding residues in these proteins. The remarkable conservation of sequence between NADPH-cytochrome P-450 oxidoreductase and ferredoxin-NADP+ reductase, coupled with the homology of the FMN-binding domain of the oxidoreductase with the bacterial flavodoxins, implies that NADPH-cytochrome P-450 oxidoreductase arose as a result of fusion of the ancestral genes for these two functionally linked flavoproteins. PMID- 3085708 TI - Purification and characterization of a serine protease (esterase B) from rat submandibular glands. AB - A new protease has been purified to homogeneity from rat submandibular gland homogenate by using DEAE-Sephadex chromatography, chromatofocusing, aprotinin Sepharose affinity chromatography, and high-performance liquid chromatography. The enzyme has been named esterase B, since it represents the second major esterolytic peak on DEAE-Sephadex chromatography of submandibular gland homogenate. It is an acidic protein (pI = 4.45) with an apparent molecular weight of 27 000. It is heat-stable and has an optimum pH of 9.5. Esterase B hydrolyzed the synthetic substrates tosyl-L-arginine methyl ester and Val-Leu-Arg-p nitroanilide (S2266). It also cleaved dog plasma kininogen to produce a kinin, identified as bradykinin on reverse-phase high-performance liquid chromatography. Esterase B, however, is only a weak kininogenase, since it had only 5% of the kininogenase activity of equimolar concentrations of glandular kallikrein and had no effect on rat mean blood pressure or on the isolated rat uterus. Esterase B activated plasminogen and had caseinolytic activity. It was inhibited by aprotinin, soybean trypsin inhibitor, lima bean trypsin inhibitor, phenylmethanesulfonyl fluoride, antipain, leupeptin, and p-tosyl-L-lysine chloromethyl ketone. On double immunodiffusion, when reacted with kallikrein and tonin antisera, esterase B showed partial identity with kallikrein but not with tonin. On immunoelectrophoresis against kallikrein antisera, esterase B formed a precipitin arc at a position different from that of kallikrein. Esterase B appears to be a trypsin-like serine protease having some homology with glandular kallikrein. PMID- 3085709 TI - Trimethoprim binding to Lactobacillus casei dihydrofolate reductase: a 13C NMR study using selectively 13C-enriched trimethoprim. AB - We have measured the 13C chemical shifts for trimethoprim molecules selectively enriched with 13C at the 2-, 4-, 5-, 6-, and 7-positions and the p-OCH3 position in their complexes with Lactobacillus casei dihydrofolate reductase in the presence and absence of coenzyme analogues. The C2 carbon shifts indicate that the pyrimidine ring is protonated at N1 in all the complexes of trimethoprim with the enzyme and coenzymes and in each case the pyrimidine ring is binding in a similar way to that of the corresponding part of methotrexate in the enzyme methotrexate complex. The C6 carbon of trimethoprim shows a large upfield shift in all complexes (3.51 to 4.70 ppm) but no shift in the complex of 2,4 diaminopyrimidine with the enzyme: these shifts probably arise from steric interactions between the C1' and C2' carbons and the H6 proton, which approach van der Waals contact in the folded conformation adopted by trimethoprim when bound to the enzyme. The large shift observed for C6 in all complexes indicates that the basic folded conformation is present in all of them. A comparison of the 13C shifts in the enzyme-trimethoprim-NADPH complex with those in the enzyme trimethoprim binary complex shows substantial changes even for carbons such as C6 and p-OCH3 (0.46 and -0.36 ppm, respectively), which are remote from the coenzyme: these are caused by ligand-induced conformational changes that may involve displacement of the helix containing residues 42-49.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085710 TI - Reduction of the buried intrachain disulfide bond of the constant fragment of the immunoglobulin light chain: global unfolding under physiological conditions. AB - The constant (CL) fragment of the immunoglobulin light chain contains only one intrachain disulfide bond buried in the interior of the molecule. The kinetics of reduction with dithiothreitol of the disulfide bond were studied at various concentrations of guanidine hydrochloride at pH 8.0 and 25 degrees C. It was found that the disulfide bond is reduced even in the absence of guanidine hydrochloride. The results of the reduction kinetics were compared with those of the unfolding and refolding kinetics of the CL fragment previously reported [Goto, Y., & Hamaguchi, K. (1982) J. Mol. Biol. 156, 891-910]. It was shown that the reduction of the disulfide bond proceeds through a species with a conformation very similar to that of the fully unfolded one and that the CL fragment undergoes global unfolding transition even in water. PMID- 3085711 TI - Non-competitive inhibition of myo-inositol transport in cultured bovine retinal capillary pericytes by glucose and reversal by Sorbinil. AB - myo-Inositol transport by retinal capillary pericytes in culture was characterized. The major myo-inositol transport process was sodium-dependent, ouabain-sensitive, and saturable at 40 mM, indicating a carrier-mediated process. The sodium ion concentration required to produce one-half the maximal rate of myo inositol uptake ([Na+]0.5) did not show dependence on the external myo-inositol concentration (22.3 mM sodium for 0.005 mM myo-inositol; 18.2 mM sodium for 0.05 mM myo-inositol). myo-Inositol transport was an energy-dependent, active process functioning against a myo-inositol concentration gradient. The kinetics of the sodium-dependent system fitted a 'velocity type' co-transport model where binding of sodium ion to the carrier increased the velocity (Vmax 28 to 313 pmol myo inositol/micrograms DNA per 20 min when [Na+] varied from 9 to 150 mM) but not the affinity for myo-inositol (Km 0.92 to 0.83 mM when [Na+] varied from 9 to 150 mM). Metabolizable hexoses (D-glucose or D-galactose; greater than 5 mM) inhibited myo-inositol uptake. Dixon-plot analysis indicated that the inhibition was non-competitive with a Ki of 22.7 mM for D-glucose and 72.6 mM for D galactose. The inhibition was significantly reversed by Sorbinil (0.1 mM), an aldose reductase inhibitor. In contrast, high concentrations of non-metabolizable hexoses (L-glucose, 3-O-methyl-D-glucose), or partially metabolizable 2-deoxy-D glucose, did not significantly inhibit myo-inositol uptake. The inhibitory effect of D-glucose or D-galactose on myo-inositol transport appeared to be related to glucose or galactose metabolism via the polyol pathway. PMID- 3085712 TI - Interaction of flavonoids with rabbit muscle phosphorylase kinase. AB - We have examined the effect of several flavonoids on the activity of phosphorylase kinase from rabbit skeletal muscle. From 14 flavonoids tested, the flavones quercetin and fisetin were found to be efficient inhibitors of nonactivated phosphorylase kinase when assayed at pH 8.2, causing 50% inhibition at a concentration of about 50 microM, while the flavanone hesperetin stimulated phosphorylase kinase activity about 2-fold when tested at 250 microM. The efficiency of quercetin in inhibiting the kinase is higher when the enzyme is stimulated either by ethanol or by alkaline pH. Both casein and troponin phosphorylation by phosphorylase kinase and the autophosphorylation of the kinase were inhibited by quercetin. In addition, quercetin was found to be a competitive inhibitor of ATP for the phosphorylation of phosphorylase b at pH 8.2. These observations suggest that the inhibitory effect of the flavone is directly on the phosphorylase kinase molecule. Trypsin-activated phosphorylase kinase was inhibited by quercetin and stimulated by hesperetin, as for the native enzyme. PMID- 3085713 TI - Effect of calcium binding on conformational changes of staphylococcal metalloproteinase measured by means of intrinsic protein fluorescence. AB - The removal by EDTA of Ca2+ from the two-tryptophan-containing metalloproteinase isolated from Staphylococcus aureus leads to an increase in its intrinsic fluorescence intensity. Based on acrylamide fluorescence quenching results, analyzed by the non-linear least-squares method, we have shown that this protein molecule undergoes irreversible conformational change upon removal of Ca2+, which include the exposure to the solvent of buried tryptophan residues. Steady-state fluorescence anisotropy measurements indicate that the loss of Ca2+ leads to a significant increase in internal mobility of previously buried tryptophan residues. PMID- 3085714 TI - Primary specificity of ancrod, the coagulating serine proteinase from the Malayan pit viper (Agkistrodon rhodostoma) venom. AB - Values of steady-state and pre-steady-state parameters for the hydrolysis of ZArgONp and ZLysONp catalysed by ancrod, the coagulating serine proteinase from the Malayan pit viper (Agkistrodon rhodostoma) venom, have been determined, between pH 2.5 and 8 (I = 0.1 M) at 21 +/- 0.5 degrees C, and analysed in parallel with those of bovine alpha-thrombin and porcine pancreatic beta kallikrein-B. In addition to the well-known coagulating behaviour, ancrod also shows catalytic properties, in the hydrolysis of ZArgONp and ZLysONp, reminiscent of those of porcine pancreatic beta-kallikrein-B. PMID- 3085715 TI - The size of human factor VIII heterodimers and the effects produced by thrombin. AB - The heterodimeric structure of factor VIII was demonstrated by two approaches. First, the native molecular weights of several partially purified fractions of factor VIII were determined by measurement of Stokes radii and sedimentation coefficients to be approx. 237 500, 201 000 and 141 000. These measured molecular weights correlated with those derived from polypeptide chain composition, in which each molecule would consist of a doublet polypeptide of Mr 83 000/81 000 plus one predominant high-Mr polypeptide of either 146 000, 120 000 or 93 000. In addition, immunoadsorption using a monoclonal antibody specific for the light chain doublet removed all of the heavy chains. Separation of the heavy chains from the light chain by EDTA further illustrated the non-covalent nature of the heterodimers. All forms had coagulant activity which was potentiated 13-15-fold by an equimolar amount of human alpha-thrombin. Thrombin converted the Mr 83 000/81 000 doublet to one of Mr 73 000/71 000, and cleaved the largest polypeptides to a transient intermediate form of Mr 93 000 which was further cleaved to polypeptides of Mr 51 000 and 43 000. Potentiation of coagulant activity was correlated with proteolytic cleavage of either or both the doublet and the Mr 93 000 polypeptides. These data indicate that human factor VIII purified from plasma consists of a group of heterodimers, composed of a light chain of Mr 83 000 (81 000) and a heavy chain which varies in size between Mr 170 000 and 93 000, each form of which is similarly potentiated and cleaved by thrombin. PMID- 3085716 TI - Catalytic properties of bovine alpha-thrombin: a comparative steady-state and pre steady-state study. AB - Values of steady-state and pre-steady-state parameters for the bovine alpha thrombin-catalyzed hydrolysis of ZArgONp and ZLysONp have been determined between pH 2.5 and 8 (I = 0.1 M) at 21 +/- 0.5 degree C. Kinetic properties of bovine alpha-thrombin have been analyzed in parallel with those of porcine pancreatic beta-kallikrein-B and bovine beta-trypsin, all acting on cationic substrates. The different primary specificity and catalytic behaviour of these three serine proteinases reflect subtle structural differences at their S1 subsite, especially at residue positions 190, 221 and 226 as well as in the 217-219 segment. PMID- 3085717 TI - Secretion of cholesteryl-ester-rich lipoproteins by the perfused livers of rabbits fed a wheat-starch-casein diet. AB - Rabbits fed a cholesterol-free semi-synthetic wheat-starch-casein diet had a high plasma cholesterol concentration; most of the cholesterol was associated with low density lipoproteins (LDL). Chemical analyses of plasma lipoproteins revealed that very-low-density lipoproteins (VLDL), intermediate lipoproteins and LDL from casein-fed rabbits contained more cholesteryl ester than that of lipoproteins isolated from chow-fed animals. The fatty acid composition of cholesteryl esters of plasma lipoproteins showed that there were higher contents of oleic acid than linoleic acids in lipoproteins from casein-fed rabbits. Lipoproteins isolated from liver perfusates of casein-fed rabbits had higher cholesteryl oleate content than lipoproteins from chow-fed rabbit liver perfusates. There was a marked increase in secretion of apolipoproteins from perfused livers of casein-fed rabbits. We conclude that the high levels of plasma cholesterol in casein-fed rabbits are of hepatic origin and that one of the hypercholesterolemic actions of dietary casein in rabbits is the induction of hepatic synthesis and secretion of cholesteryl-ester-rich lipoproteins. PMID- 3085719 TI - Anion effects on the reaction of lecithin-cholesterol acyltransferase with discoidal complexes of phosphatidylcholines . apolipoprotein A-I . cholesterol. AB - Discoidal complexes of phosphatidylcholine (PC) . apolipoprotein A-I . cholesterol were prepared with egg PC, palmitoyloleoylPC, dipalmitoylPC, or dimyristoylPC, and were used as substrates of purified lecithin-cholesterol acyltransferase to investigate the effects of neutral salts on the enzymatic reaction. Sodium fluoride, chloride and bromide concentrations up to 1 M, did not affect the properties of the substrate particles, but caused marked and distinct changes in the activity of the enzyme with the various PC particles. The effects of salts were largely due to the anions, which followed the order of the lyotropic series in their inactivating capacity: F- less than Cl- less than Br- less than NO3- less than I- less than SCN-. Sodium salts (F-, Cl-, and Br-) produced a very large increase in the pH optimum of the enzymatic reaction (7.4 to at least 8.5) essentially obliterating the ionization of a functional group with pK of 8.1. The kinetics of the enzymatic reaction revealed major differences among the PC particles, and different responses of their kinetic parameters with increasing salt concentrations. The conclusions reached in this work are the following: (1) The relative reactivity of PC substrates, in discoidal particles, with lecithin-cholesterol acyltransferase depends strongly on the concentration and type of salts in the medium. (2) Anions (in lyotropic series) rather than cations affect the enzymatic reaction. (3) There are functional groups with pK of 8.1 which are affected markedly in their ionization behavior by anion binding. (4) The active site of lecithin-cholesterol acyltransferase and its interaction with anions are affected by the exact nature of the PC-apolipoprotein interface. PMID- 3085718 TI - Effects of high-dose ethinyl estradiol on serum concentrations and hepatic secretion of the very-low-density lipoprotein, triacylglycerol, cholesterol, and apolipoprotein A-I in the rat. AB - Female and male rats were treated with ethinyl estradiol (5.0 mg/kg daily for 5 days). Control animals were pair fed to compensate for the reduction in food intake induced by the estrogen, or were fed ad libitum. Treatment with ethinyl estradiol reduced total cholesterol and apolipoprotein A-I concentrations in the serum of female and male animals. The concentrations of serum and hepatic triacylglycerol were depressed markedly in animals of both sexes in groups treated with ethinyl estradiol, compared to the control group fed ad libitum. Compared to the pair-fed controls, however, ethinyl estradiol had only a very minor further reduction on serum triacylglycerol concentration. In male and female rats, the synthesis and secretion of triacylglycerol by the liver was, in comparison to the pair-fed controls, stimulated by estrogen, whereas the secretion of unesterified cholesterol was unaffected by any of the treatment regimens. The synthesis and secretion of total cholesteryl esters by livers from male and female rats was increased by treatment with ethinyl estradiol. The hepatic synthesis and secretion of VLDL triacylglycerol and cholesteryl ester was stimulated by ethinyl estradiol in male and female rats, and the VLDL particle was enriched with cholesteryl ester. Treatment with the high-dose estrogen increased the secretion of apolipoprotein A-I by livers from female rats. It is suggested that the depression in the serum concentrations of cholesteryl esters and apolipoprotein A-I is the result of increased rates of hepatic and/or peripheral catabolism of these components and that the hepatic production rates were increased or unaffected in animals administered high doses of ethinyl estradiol. Since the secretion of apolipoprotein A-I by livers from male rats was unaffected by treatment with ethinyl estradiol, the response to estrogen may be sex related. PMID- 3085720 TI - Regulation of thromboxane A2 biosynthesis in platelet-free human monocytes and the possible role of polypeptide growth factor(s) in the induction of cyclooxygenase system. AB - It has previously been shown that platelet-free human monocytes, when properly incubated in the presence of animal and human sera, became capable of producing large amounts of thromboxane A2 and prostaglandin E2. The characteristics of these processes are reported here. Prostaglandin biosynthesis was time and cell concentration dependent; 24 h of incubation at 37 degrees C and 0.5 X 10(6) cells per ml medium were found to give the most reproducible results. Human monocytes produced thromboxane A2 and prostaglandin E2 in a typical ratio which ranged from 2.0 to 5.0 (28 experiments). Animal and human sera were similarly effective, while serum obtained from platelet-free blood was much less active. The activity of all sera tested was stable to heating (100 degrees C for 2-10 min) and extreme pH values (pH 2 and 11). It was unstable when the serum was heated at pH 11 and after 2-mercaptoethanol treatment. These observations prompted us to check the effect of polypeptide growth factors having properties similar to those reported above, such as platelet-derived growth factor, fibroblast growth factor, epidermal growth factor as well as insulin and transferrin. None of these, alone or in various combinations, was capable of eliciting a stimulation comparable with that of serum. Stimulation due to sera was, as expected, dose dependently inhibited by acetylsalicylic acid and more efficiently by indomethacin; unexpectedly it was also inhibited by protein synthesis inhibitors such as actinomycin D and cycloheximide in conditions under which no toxic effect of the drugs was evident. On the basis of these results we conclude that: (a) polypeptide growth factor(s) with a molecular weight at least 30 000 (as judged by Amicon ultrafiltration) is involved in the regulation of prostaglandin biosynthesis); (b) such a factor(s) acts by inducing rather than by activating the cyclooxygenase system. PMID- 3085721 TI - Lipid peroxidation in rat uterus. AB - Lipid peroxidation in rat uterus has been studied using NADPH- and ascorbate induced systems. Lipid peroxidation in rat uterus is low as compared to rat liver. Uterus is more sensitive to ascorbate-induced lipid peroxidation than that induced by NADPH. Uterus contains lower amounts of phospholipids and has a lesser degree of unsaturation in lipids. Co-factor studies show that Fe2+ is more important for ascorbate-induced lipid peroxidation. Endometrium is more sensitive to ascorbate-induced lipid peroxidation than myometrium. It also contains more total lipids and phospholipids besides having a higher degree of unsaturation in the lipids as compared to myometrium. Among the subcellular fractions, mitochondria are more prone to ascorbate-induced lipid peroxidation, whereas microsomes are more sensitive to NADPH-induced lipid peroxidation. Uteri from old rats (24 months) and pregnant rats are more resistant to lipid peroxidation than those from 3-month-old control rats. Uterus of pregnant rats contains more factors which inhibit lipid peroxidation and also has a lesser degree of unsaturation in lipids compared with uterus of control rats. The possible consequences of the resistance of uterus to lipid peroxidation, especially during pregnancy and senescence, are discussed. PMID- 3085722 TI - Evidence for a catalytic role of phospholipase A in phorbol diester- and zymosan induced mobilization of arachidonic acid in mouse peritoneal macrophages. AB - Inositol phospholipid degradation and release of phospholipid-bound arachidonic acid was induced in intact peritoneal macrophages by exposure to phorbol myristate acetate (PMA) or zymosan particles. PMA, known to activate protein kinase C, selectively enhanced the deacylation of phosphatidylinositol (i.e., degradation by phospholipase A), while zymosan particles enhanced degradation via both phospholipase A and inositol lipid phosphodiesterase (phospholipase C). The release of arachidonic acid was found to correlate with the degradation of phosphatidylinositol by the phospholipase A pathway and could be dissociated from the phospholipase C-catalyzed cleavage of inositol phospholipids in several experimental situations: (i) when PMA was the stimulus, (ii) by the difference in Ca2+ dependence between the two enzymatic processes when zymosan was the stimulus and (iii) by the parallel inhibition by chlorpromazine of the phospholipase A pathway and arachidonic acid release, but not inositol phospholipid phosphodiesterase. In addition, phloretin, a reported inhibitor of protein kinase C, was found to inhibit arachidonic acid release and the deacylation of phosphatidylinositol. The results are consistent with a model in which arachidonic acid release is mediated by phospholipase(s) A and in which PMA or the phosphodiesterase-catalyzed degradation of phosphoinositides causes activation of the phospholipase A pathway via protein kinase C. PMID- 3085723 TI - Relative degradation of different arachidonoyl molecular species of choline glycerophospholipids in opsonized zymosan-stimulated rabbit alveolar macrophages. AB - The relative degradation of arachidonoyl molecular species of glycerophospholipids prelabeled with [3H]20:4 caused by opsonized zymosan was studied in rabbit alveolar macrophages using a recently developed high performance liquid chromatographic method. The opsonized zymosan caused the release of [3H]20:4 only from choline glycerophospholipids, no significant changes being observed in the radioactivities of other glycerophospholipids and triacylglycerol. Choline glycerophospholipids were resolved into seven arachidonoyl molecular species, which differed as to the alkyl ether or acyl residue bound at the 1-position, by high-performance liquid chromatography. Arachidonate was predominantly located in the alkyl type having 16:0 at the 1 position which comprised more than half of the total arachidonoyl molecular species of choline glycerophospholipids. The radioactivities of all arachidonoyl molecular species of choline glycerophospholipids, except for the 18:2-20:4 and 18:1-20:4 species of diacylglycerophosphocholine, decreased to 80-85% of the control values as a result of the challenge with opsonized zymosan for 1 h. However, 50% of the released 20:4 came from the 16:0-20:4 species of alkylacylglycerophospholipids, which were the most predominant species of choline glycerophospholipids. The present results indicate that the 16:0-20:4 species of alkylacylglycerophosphocholine is a significant source of arachidonate and 1-O alkyl-2-lysoglycerophosphocholine, the precursor of the platelet-activating factor, relative to other arachidonoyl species in activated alveolar macrophages. PMID- 3085724 TI - The level of beta-alanine aminotransferase activity in regenerating and differentiating rat liver. AB - beta-Alanine aminotransferase from rat liver was purified to electrophoretic homogeneity. The immunological and kinetic properties of this enzyme were similar to those of the enzyme from rat brain. However, the liver enzyme transaminates from beta-alanine to 2-oxoglutaric acid, while the brain enzyme transaminates from gamma-aminobutyric acid. beta-Alanine aminotransferase activity in regenerating rat liver was lower than that in control rat liver. Activity of this enzyme, as well as of other uracil-catabolizing enzymes (Weber, G., Queener, S.F. and Ferdinandus, A. (1970) in Advances in Enzyme Regulation (Weber, G., ed.), Vol. 9, pp. 63-95, Pergamon Press, Oxford), was low in newborn rat liver and increased about 5-fold, reaching the level observed in adult rat liver. beta Alanine and prednisolone induced beta-alanine aminotransferase in rat liver. PMID- 3085725 TI - Purification and properties of poly(ADPribose) synthetase from sheep testis. AB - Poly(ADPribose) synthetase has been purified to apparent homogeneity from sheep testis by a simple procedure using three chromatographic steps (DNA-agarose, blue Sephadex G-150 and phosphocellulose P11). A concentrated enzyme preparation, 3.5 mg, with a specific activity of 1265 nmol/min per mg was obtained from 250 g of tissue. DNA was absolutely required for enzyme activity. The half-maximal activation occurred at the concentrations of 11 micrograms/ml for highly polymerized calf thymus DNA and 2 micrograms/ml for sonicated calf thymus DNA. The Km for NAD was 57 microM. The molecular weight was 120 000, determined by gel electrophoresis in the presence of sodium dodecyl sulfate. Amino acid analysis indicated that the main amino acid species of sheep testis enzyme were very similar to those of enzymes from other sources. PMID- 3085726 TI - Organization of glycosaminoglycan chains in a chondroitin sulfate-dermatan sulfate proteoglycan from bovine aorta. AB - A chondroitin sulfate-dermatan sulfate proteoglycan was isolated from bovine aorta intima by extraction of the tissue by 4 M guanidine hydrochloride. The proteoglycan was purified by CsCl isopycnic centrifugation followed by gel filtration and ion-exchange chromatography. The proteoglycan had 21.9% protein, 22.1% uronate, 21.4% hexosamine and 10.8% sulfate. Glycosaminoglycan chains obtained from the proteoglycan by beta-elimination were resolved by gel filtration into two fractions, one containing chondroitin 6-sulfate with an approximate molecular weight of 49 000 and the other containing chondroitin 4 sulfate and dermatan sulfate in a proportion of 2:1 with an approximate molecular weight of 37 000. Digestion of the proteoglycan by chondroitinase ABC or AC yielded a protein core with similar composition and behavior in gel filtration and SDS-polyacrylamide gel electrophoresis. An approximate molecular weight of 180 000 was estimated for the core protein. Dermatan sulfate chains with an approximate molecular weight of 10 000 were observed only in the digest of chondroitinase AC. Limited trypsin hydrolysis of the proteoglycan yielded three peptide fragments containing chondroitin 6-sulfate, chondroitin 4-sulfate and dermatan sulfate in varied proportions. A tentative structure for the proteoglycan was suggested. PMID- 3085727 TI - Resolution of racemic gossypol and interaction of individual enantiomers with serum albumins and model peptides. AB - Racemic gossypol has been resolved by HPLC separation of diastereomeric (-) norepinephrine adducts on a reverse-phase column. The binding constants for the interaction of the three gossypol forms (+, - and +/-) with human and bovine serum albumins have been determined by fluorescence quenching studies. The KD values demonstrate that all three forms bind equally effectively to the two proteins, suggesting an absence of chiral discrimination in albumin-gossypol interactions. Circular dichroism studies of (+)-gossypol binding to the model dibasic peptides, Boc-Lys-Pro-Aib-Lys-NHMe and gramicidin S, suggest that distortions of binaphthyl geometry may occur only for specific orientations of interacting residues at the receptor site. PMID- 3085728 TI - Characterization of pulmonary carbonyl reductase of mouse and guinea pig. AB - Carbonyl reductases were purified from mouse and guinea pig lung. The mouse enzyme exhibited structural and catalytic similarity to the guinea pig enzyme: tetrameric structure consisting of an identical 23 kDa subunit; basicity (pI of 8.8); low substrate specificity for aliphatic and aromatic carbonyl compounds; dual cofactor specificity for NADPH and NADH; stereospecific transfer of the 4 pro S hydrogen of NADPH; and sensitivity to pyrazole, 2-mercaptoethanol and ferrous ion. Although 3-ketosteroids were extensively reduced by the mouse enzyme but not by the guinea pig enzyme in the forward reaction, the two enzymes similarly oxidized some alicyclic alcohols such as acenaphthenol, cyclohex-2-en-1 ol and benzenedihydrodiol in the presence of NADP+ and NAD+. A partial similarity between the two enzymes was observed immunologically, using antibodies against the purified guinea pig enzyme. The lung enzymes differ in several aspects from other oxidoreductases from extrapulmonary tissues. The immunoreactive protein was detected only in lung of the tissues of the two species. PMID- 3085729 TI - The effect of tetradecanoylphorbol acetate on calcium-ion mobilization, protein phosphorylation and cytoskeletal assembly induced by thrombin or arachidonate. AB - Tetradecanoylphorbol acetate (TPA) activates primarily only the protein kinase C pathway not the calcium ion-dependent pathway in platelets. The net effect of this split activation is that only the pseudopodal cytoskeleton assembles, not the contractile cytoskeleton needed for rapid secretion. In this study, platelets were first activated with TPA, then activated secondarily with either thrombin or arachidonate and the subsequent dense body secretion, calcium-ion mobilization, protein phosphorylation and cytoskeletal assembly compared to these same processes in control platelets activated solely with either thrombin or arachidonate. Secretion was reduced as the length of time between the primary and secondary activation was increased; but at a 2-3 min interval, where the activation by TPA was essentially complete, the reduction in the total radiolabeled serotonin secreted was small. Furthermore, nearly normal cytosolic calcium-ion increases, phosphorylation of myosin light chain and contractile cytoskeletal development were induced by thrombin or arachidonate after this interval. Prior treatment of the platelets with 100 microM acetylsalicylate to block the cyclooxygenase-dependent pathway caused minor reduction in dense-body secretion induced by TPA or thrombin or the combination of both, but otherwise the relative results were comparable to the untreated platelets. Therefore, short term prior activation of gel-filtered platelets with TPA, even at concentrations in excess of 100-times that required to saturate protein kinase C, does not prevent normal activation of the calcium ion dependent processes through either the cyclooxygenase-dependent or -independent pathway. Longer-term preincubations with TPA differentially inhibit the secretion response induced by thrombin and arachidonate. PMID- 3085730 TI - Effect of protein kinase C activation and Ca2+ mobilization on hexose transport in Swiss 3T3 cells. AB - Down-modulation of Ca2+-activated, phospholipid-dependent protein kinase (protein binase C), which was accomplished by pretreatment with phorbol-12,13-dibutyrate for 24 h, resulted in the loss of a phorbol ester-induced stimulation of hexose transport activity in Swiss 3T3 cells. In these cells, however, platelet-derived growth factor as well as Ca2+ ionophore A23187 were still able to induce stimulation of hexose transport activity accompanied by the elevation of intracellular free Ca2+ concentration. Since chelation of extracellular Ca2+ inhibited this stimulation, inflow of extracellular Ca2+ into cytoplasm seemed to be essential for the stimulatory effect of platelet-derived growth factor and A23187 on hexose transport. Epidermal growth factor and insulin also stimulated hexose transport activity regardless of the absence of protein kinase C. However, in the case of epidermal growth factor, intracellular Ca2+, but not extracellular Ca2+, was found to be necessary for the stimulation. On the other hand, insulin stimulated the hexose transport independent of both intra- and extracellular Ca2+. PMID- 3085732 TI - Priming of leukocytes selectively increases the level of some interferon-alpha subtypes and not others. AB - The effect of pretreatment with interferon (IFN) ('priming') on the production of individual IFN subtypes was studied in subpopulations of human peripheral blood mononuclear cells and in the myeloid cell line KG-1. It was found that priming had a selective enhancing effect on the production of certain IFN-alpha subtypes (IFN-alpha 20K and IFN-alpha 21K) and not on others. KG-1 cells produce both IFN alpha and -beta; however, only the production of IFN-alpha was enhanced by priming with either IFN-alpha, beta or gamma. PMID- 3085731 TI - Synchronous oscillation of the cytoplasmic Ca2+ concentration and membrane potential in cultured epithelial cells (Intestine 407). AB - Cultured epithelial Intestine 407 cells exhibit regular oscillations of the membrane potential with repeated hyperpolarizations. These hyperpolarizations were inhibited not only by K+ channel blockers (tetraethylammonium and nonyltriethylammonium) but also by inhibitors of the Ca2+-activated K+ channel (quinine and quinidine). Using Ca2+-selective microelectrodes, cyclic increases in the cytosolic free Ca2+ concentration of more than 1 X 10(-6) M were found to coincide with the cyclic membrane hyperpolarizations. Thus, it appears that the potential oscillation is brought about by the oscillation of the intracellular free Ca2+ level which induces periodic activation of the Ca2+-dependent K+ channels. Neither the deprivation of extracellular Ca2+ nor the application of Ca2+ channel blockers (Co2+ and Ni2+) abolished the potential oscillation. Mitochondrial inhibitors (KCN, NaN3, antimycin A, FCCP and dinitrophenol) inhibited the potential oscillation, whereas glycolytic inhibitors (iodoacetic acid and NaF) had no effects. Caffeine and oxalate, which affect the microsomal Ca2+ transport, failed to exert any effect upon the potential oscillation. It is concluded that the cytosolic Ca2+ oscillation results from cyclic releases of Ca2+ from the intracellular storage site, which depends upon mitochondrial activities. PMID- 3085733 TI - [Biosynthesis in the rat liver of a common form of monooxygenase induced by xenobiotics of a methylcholanthrene series]. AB - Injection of Wistar rats with five structurally different inducers of methylcholanthrene-type (polycyclic aromatic and heterocyclic hydrocarbons, chloro-derivatives of biphenyl and dibenzo-p-dioxin) results in the de novo synthesis of two P-448 hemoproteins (molecular weight 56 000 and 53 000 Da) differing in their functional and immunochemical properties in liver microsomes. A comparison of catalytic and immunochemical characteristics of five cytochrome P 448 forms (Mr = 56 000 Da) as well as the data from electrophoretic, proteolytic and inhibitory analyses revealed no differences in the preparations used, with the exception of 2,3,7,8-tetrachloro-dibenzo-p-dioxin-induced microsomes characterized by a low level of this cytochrome P-448 form and a higher molecular activity as compared with 3,4-benzpyrene and 7-ethoxyresorufin-induced microsomes. The experimental results do not confirm the hypothesis on the feasibility of induced synthesis of a variety of individual forms of monooxygenase that would correlate with the number of structural variants of inducers. PMID- 3085734 TI - [Changes in DNA and purine nucleotide synthesis in lymphoid cells and sensitivity to glucocorticoids associated with the impairment of differentiation and immune function in mice during tumor growth. Spleen T- and B-lymphocytes]. AB - Biochemical impairments in spleen immunocompetent cells (T- and B-lymphocytes) were revealed in host (C3HA mice) of transplantable and ortoaminoazotoluol induced hepatomas in the course of their growth. As soon as hepatoma emerged (chemical carcinogenesis), the activity of adenosine deaminase and purine nucleoside phosphorylase in T- and B-lymphocytes were found to be reduced 2-6 and 7-10-fold, respectively in parallel with the impairment of their immune system. These alterations were accompanied by the increase in concentrations of dGTP in T lymphocytes (5.4-fold) and of dATP in B-lymphocytes (4-fold) as well as with the inhibition of DNA synthesis, predominantly in T-lymphocytes. In both T- and B lymphocytes, the dCTP pool was decreased. In the spleen, T- and B-lymphocytes of mice carrying transplantable 22 hepatoma 22 by the moment of its maximal growth (5th day), the DNA synthesis was inhibited as revealed by the reduction of (a) thymidine kinase activity, (b) rate of the labeled thymidine incorporation into DNA, and (c) intracellular dTTP and dCTP concentrations. In latter periods (from 8th day up to the moment of death), drastic stimulation of DNA synthesis in spleen T- and B-lymphocytes was observed irrespective of the impairments in the immune function and the decrease of the adenosine deaminase activity. In the course of growth of both transplantable and induced solid hepatomas in host spleen T- lymphocytes, the activity of the CTP-dependent thymidine kinase isoenzyme increased, coinciding in time with the activation of antigen-specific T suppressors in the same organ. PMID- 3085735 TI - [Prostaglandin H synthetase as a multisubstrate enzyme. Fluorimetric study of enzyme kinetics]. AB - The kinetics of a multisubstrate enzymatic reaction catalyzed by prostaglandin H synthase (PGH-synthase, EC 1.14.99.1) was studied, using homovanillic acid, a new electron donor for the given system. Homovanillic acid was shown to be a participant in a reaction with arachidonic acid/O2 stoichiometric ratios and is oxidized to a readily fluorescing product with an absorbance maximum (excitation) at 315 nm and fluorescence maximum at 425 nm. This allows for determination of the rate of enzymatic reaction with the sensitivity exceeding by one order of magnitude that of polarographic or spectrophotometric assays. Using fluorescent techniques, the dependence of the rate of PGH-synthase reaction on substrate (arachidonic acid, O2 and homovanillic acid) concentrations was studied, and the corresponding Km values were determined. The effect of Tween-20 and Lubrol PX concentrations on the reaction rate were examined. It was shown that with a decrease in the surfactant concentration the reaction rate increases. PMID- 3085736 TI - [Inhibition by melanin of lipid photo-oxidation]. AB - Removal of melanosomes from retinal pigment epithelium cells is accompanied by a sharp rise in the rate of VIS light-induced lipid peroxidation. The synthetic DOPA-melanin effectively suppresses the UV light-induced lipid peroxidation of cardiolipin not only through a passive decrease of irradiation (optical screening), but also by active chemical inhibition of the reaction. It is assumed that the observed active inhibition is due to the interaction between DOPA melanin and the free radical products generated in cardiolipin upon UV illumination. It is concluded that the high photoresistance of melanin-containing cells of retinal pigment epithelium is due to the ability of melanosomes to exert strong inhibition of photo-induced lipid peroxidation. PMID- 3085737 TI - [A period of urgent postnatal adaptation as a critical stage of human ontogenesis]. AB - The infant's state immediately after delivery is characterized by critical shifts of homeostasis parameters: decompensated mixed acidosis, pathologic indices of gaseous blood condition (arterial hypoxemia and hypercapnia), spontaneous postnatal hypothermia. Qualitative change of functional systems after delivery is accompanied by expressed tense of adaptation and regulation mechanisms and by centralization of cardiac rhythm control. The use of mathematical analysis of cardiac rhythm made it possible to find out that the change of degree of adaptation tense in the process- of postnatal period obeys the exponential dependence; moreover, the duration of transitional process of healthy newborns is 1 hour, but it considerably increases in case of hypoxia. After comparison of cardiac rhythm indices of these two groups of newborns it has been pointed out that mechanisms of adaptation after delivery are equal and they are based on the growing activity of central regulation processes. The dynamics of transitional process such as the period of postnatal adaptation indicates the reserve possibilities of infant and helps to reveal pre-nosological forms of disadaptational syndrome. PMID- 3085738 TI - Growth hormone response to sodium valproate in chronic schizophrenia. AB - The hypothesis of a gamma-aminobutyric acid (GABA) involvement in the pathophysiology of schizophrenia has been recently proposed but not confirmed. As GABA has been shown to affect basal growth hormone (GH) secretion in humans, the assessment of plasma GH response to a GABAergic drug, such as sodium valproate (SV), in schizophrenic subjects might be a tool with which to investigate central GABA activity in this illness. For this purpose, we administered orally 800 mg of SV or placebo to 13 chronic schizophrenics and to 10 normal controls, and measured plasma GH levels before and after the drug administration. SV enhanced basal GH secretion in healthy male volunteers, but not in chronic schizophrenics. These results suggest a defect of the endogenous GABA system in chronic schizophrenia. Whether the reduced responsiveness observed represents a primary defect or a secondary alteration of the GABA system in schizophrenia is as yet unknown. PMID- 3085739 TI - Is there paradoxical growth hormone response to thyrotropin-releasing hormone in depression? AB - Several investigators have reported a paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH) in depressed patients, but other studies have failed to confirm this. In the present study, the GH response to TRH was studied in depressed patients and normal subjects. The rate of paradoxical GH response to TRH in depression was no different than that observed in control subjects. This was the case whether the data was examined using mean values or using frequency of abnormal responses. Patients with blunted thyrotropin (TSH) responses did not differ in GH release from patients with normal TSH response. A variety of factors may have contributed to the earlier reports of a positive GH response to TRH, including the definition of paradoxical GH release and the fact that depressed patients exhibit more frequent spontaneous diurnal GH release than do normal subjects. PMID- 3085741 TI - [Selective glutaraldehyde blockade of the sensitivity of arteries to blood flow velocity]. AB - The possibility of selective blockade of arterial sensitivity to flow rate was investigated. The method under study was based on the ability of glutaraldehyde to increase cellular rigidity. As flow-induced arterial dilatation depends on endothelial sensitivity to force, the increased rigidity of endothelial cells leads to the reduction of the dilator stimulus. It was shown that the treatment of endothelium with dimerized glutaraldehyde (0.01-0.03%, 30 sec) removed flow induced arterial dilatation, without abolishing acetylcholine-evoked dilatation. PMID- 3085740 TI - Gonadotropin uptake in genetic and irradiation models of ovarian tumorigenesis. AB - Genetic and irradiation models of ovarian tumorigenesis were investigated for evidence that elevated gonadotropins have a role in tumorigenesis. Wx/Wv mice lack oocytes at birth, develop complex mesothelial adenomas by 6 mo, and additional ovarian tumor types later. Uptake of iodinated human chorionic gonadotropin (125I-hCG) was measured in mice aged 1 to 30 mo, and uptake iodinated human follicle-stimulating hormone (125I-hFSH) was measured in mice aged 1 to 12 mo. Gonadotropin uptake by Wx/Wv ovaries in vivo declined quickly and was undetectable by 6 mo. Irradiated ovaries rapidly lost oocytes and follicular structures, formed mesothelial adenomas by 5 mo, and later formed additional types of ovarian tumors. In the irradiation model, 125I-hCG uptake also declined quickly and was undetectable by 3 mo of age. Neither the surface nor the tubular epithelium of the mesothelial adenoma were consistently labeled by 125I-hCG in autoradiography studies with either model. Although these data do not exclude an acute role for gonadotropins in initiation of preneoplastic events, they do indicate that ovarian cells do not require chronic gonadotropin stimulation during subsequent tumorigenesis. These findings are discussed in relation to additional models of ovarian tumorigenesis. PMID- 3085742 TI - [Interaction of antidepressants and anticonvulsants in anticonvulsive and anti reserpine tests]. AB - Combined use of carbamazepine (unlike valproat-Na) and antidepressants pyrazidole (pirlindol) or imipramine increased anticonvulsive and antireserpine activity. PMID- 3085743 TI - Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype. AB - Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30 year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non-O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection. PMID- 3085744 TI - Carrier detection in hemophilia A: a cooperative international study. II. The efficacy of a universal discriminant. AB - Factor VIII (F.VIII) and von Willebrand factor (VWF):Ag data collected by eight laboratories on a total of 336 obligatory carriers of hemophilia A and 137 normal women were used to answer several questions concerning the construction of linear discriminants for carrier detection. It was found: that a "universal" linear discriminant can be constructed which is suitable for use in all laboratories and is nearly as effective as laboratory-specific discriminants; that inclusion of age and ABO blood type data improved the efficacy of these discriminants; that substitution of alternative assays for F.VIII and VWF:Ag did not generally improve the efficacy of the discriminants over that obtained using the bioassay for F.VIII:C and Laurell's immunoassay for VWF:Ag; that linear discriminants were far more effective than discriminants based on the F.VIII:C/VWF:Ag ratio. A step wise procedure is given which any laboratory may follow in using the universal discriminant for carrier detection. PMID- 3085745 TI - Purification and characterization of human platelet glutathione-S-transferase. AB - A glutathione-S-transferase was isolated and purified to homogeneity from human platelets. With a combination of ammonium sulfate fractionation and chromatographic methods, 0.2 mg of pure enzyme was obtained from 9 X 10(11) platelets with a 12% recovery. The purified enzyme had a specific activity of 7.5 U per milligram, representing an approximately 1,100-fold purification. The enzyme was found to be anionic, with an isoelectric point of 4.6. With reduced glutathione as a co-substrate, platelet glutathione-S-transferase was most active with the synthetic substrate, 1-chloro-2,4-dinitrobenzene, less active with 1,2 dichloro-4-nitrobenzene, and essentially inactive with nitroglycerin and 1,2 epoxy-3-(p-nitrophenoxy)-propane. The pH optimum for activity with glutathione and 1-chloro-2,4-dinitrobenzene was 7.0. Indomethacin (1-(p-chlorobenzoyl)-5 methoxy-2-methyindole-3-acetic acid), a chlorobenzene derivative, noncompetitively inhibited human platelet glutathione-S-transferase with an apparent KI of 0.23 mmol/L. This study represents the first complete purification and characterization of a glutathione-S-transferase from platelets. The presence of this enzyme in the platelet, within which high concentrations of reduced glutathione coexist, suggests the potential importance of the platelet in detoxification reactions and in the synthesis of the glutathione adducts of leukotriene metabolism. PMID- 3085746 TI - Lipoxygenase metabolites of arachidonic acid modulate hematopoiesis. AB - Lipoxygenase (LPO) metabolites of arachidonic acid participate in the activation and/or proliferation of a variety of cell types. In this study, we examined the role of LPO metabolites in controlling myelopoiesis and erythropoiesis in vitro. Monocyte depleted cells (MDC) prepared from human whole blood or whole mononuclear cells from human bone marrow were cultured in methylcellulose in the presence of various growth factors. Conditioned media containing human colony stimulating factors (CSF) or the tumor-promoting phorbol ester, phorbol myristate acetate (PMA), were added to induce myelopoiesis. Semipurified human erythropoietin (EPO) was added along with an endogenous source of burst-promoting activity (BPA) to induce erythropoiesis. The LPO inhibitor BW755C blocked all types of colony formation in a dose-dependent manner, with ID50 of 20 and 5 micrograms/mL for myeloid and erythroid colonies, respectively. MDC depleted of T cells were similarly inhibited by BW755C. Similar results were seen with two other LPO inhibitors, 1-phenyl-3-pyrazolidone and butylated hydroxyanisole. A fourth LPO inhibitor, nordihydroguaiaretic acid, inhibited at higher concentrations. Indomethacin, at concentrations that inhibit cyclooxygenase, had no significant effect, either alone or in combination with the LPO inhibitors. These results suggest that certain LPO products may be important mediators of both CSF- and PMA-induced myelopoiesis, and of BPA/EPO-induced erythropoiesis. PMID- 3085747 TI - Effects of therapy with T101 ricin A-chain immunotoxin in two leukemia patients. AB - Two leukemia patients, refractory to chemotherapy, were treated with T101-ricin A chain immunotoxin (T101 IT). Patient 1 (T-ALL) received a single 13.5 mg dose of T101 IT IV (12-hour infusion). Patient 2 (B-CLL) was treated with a daily 25 mg dose of T101 IT IV (two-hour infusion) over three consecutive days. Patient 2 also received 300 mg of chloroquine IM on days two and three as enhancer. In vivo binding of T101 IT was demonstrated by FACS analysis using either an antimouse Ig FITC or anti-A-chain-FITC antibodies. Following IT therapy, the expression of T65 antigen on target cells dropped to 50% and 20% of pretreatment levels, respectively. In patient 1, circulating blast cells remained unsaturated during therapy while in patient 2, cells were fully saturated for four to six hours following each infusion. Pharmacokinetic studies showed a rapid clearance of T101 IT after IV administration. Antimouse and anti-A-chain antibodies could not be detected. There were no treatment-related adverse effects. In patient 1 a rapid but transient decrease of target cells was observed, possibly related to the administration of the antibody part of T101 IT. In contrast, patient 2 showed a 40% reduction of the lymphocyte count, which remained stable over a period of 2 weeks. Such a clinical benefit following IT therapy in patient 2 could be ascribed to the absence of circulating free antigen and the complete saturation of target cells. PMID- 3085748 TI - Immunoglobulin class switch from IgG to IgA in a patient with smoldering multiple myeloma. AB - Serum of a 67-year-old male patient with smoldering multiple myeloma was shown to contain two monoclonal immunoglobulins, IgG and IgA. For the initial seven months, monoclonal IgG was predominantly elevated. During the next one year and eight months, however, serum concentration of the monoclonal IgA increased, with a concomitant decrease of IgG. N-terminal amino acid sequences of heavy and light chains separated from monoclonal IgG and IgA were analyzed. Both light chains were lambda-type and showed identical amino acid sequences of variable regions. The heavy chains also had the same N-terminal amino acid sequence between IgG and IgA. These results strongly suggest that two monoclonal proteins, IgG and IgA, in this patient were produced by B lymphocytes within a clone and that class switch from IgG to IgA in immunoglobulin production during B cell differentiation has taken place in the clinical course of this case. PMID- 3085750 TI - Substrate for endothelial prostacyclin production in the presence of platelets exposed to collagen is derived from the platelets rather than the endothelium. AB - Interactions between vascular endothelial cells and blood platelets have been investigated using a model microcirculation consisting of microcarrier beads colonized with human umbilical vein endothelial cells (HUVECs) and perfused with washed platelet suspensions. To simulate the effects of endothelial desquamation and exposure of subendothelium, fibrillar collagen in suspension was coinjected with the platelets. In this model, neither the passage of platelets alone nor collagen alone stimulated prostacyclin (PGI2) production by the HUVECs. Platelets activated by coinjection with collagen released thromboxane A2 (TXA2), and this was associated with the simultaneous production of PGI2 by the HUVECs. By means of double-isotope experiments with [3H]arachidonic acid (AA) incorporated into platelets and [14C]-AA into HUVECs, it was shown that all the PGI2 generated was derived from platelet AA and/or endoperoxides. This interpretation was strengthened by the finding that PGI2 production was not prevented by treatment of HUVECs with indomethacin followed by perfusion with collagen-stimulated platelets. AA metabolites in double-isotope label experiments were further characterized by reverse-phase chromatography, and it was shown that both cyclooxygenase and lipoxygenase products of the HUVECs were derived from platelet membrane lipid. Thrombin regularly produced transient PGI2 release, but showed rapid tachyphylaxis. Platelet-derived compounds including ADP, ATP, and platelet activating factor (PAF) did not produce PGI2 release by HUVECs in this system. Thus, the transfer of AA and metabolites from collagen-stimulated platelets is likely to be the mechanism for PGI2 production in the context of minor degrees of endothelial desquamation. PMID- 3085749 TI - Thrombin causes subsecond changes in protein phosphorylation of platelets. AB - We have developed a general quenched-flow approach to study platelet function as early as 0.3 seconds after stimulation. Phosphorylation of 20- and 40-kd proteins has been analyzed during the first five seconds of platelet response to thrombin from 0.1 to 5.0 U/mL and compared with the progress of aggregation and serotonin secretion. The onset time for aggregation and phosphorylation of both proteins was less than one second, although with lowest (less than 0.5 U/mL) thrombin levels, a lag of up to 0.6 seconds occurred before 40K phosphorylation increased. The thrombin sensitivity of aggregation and 20K phosphorylation was approximately twice that of 40K phosphorylation, with Ka values of 0.51 and 0.53 v 1.10 U/mL, respectively. External calcium was necessary for maximal 20K phosphorylation, since EDTA inhibited this by 30%. The 40K phosphorylation was not affected by EDTA. Platelet activation by thrombin thus induced biochemical changes well before one second. The quenched-flow approach may help to reveal relationships between phospholipase activation, calcium fluxes, and protein phosphorylation during these early periods of platelet function. PMID- 3085751 TI - Microvascular permeability increase in rat skin: inhibition by flunarizine, a Ca2+ entry blocker. PMID- 3085752 TI - PCB congeners, hexachlorobenzene, and organochlorine insecticides in human fat in Italy. PMID- 3085753 TI - Toxicity of CdCl2, CdEDTA, CuCl2, and CuEDTA to marine invertebrates. PMID- 3085755 TI - Hypercapnic ventilatory response in unanesthetized normal hamsters. AB - In order to measure the hypercapnic ventilatory response (HCVR) in experimental animals, it is desirable that the animals be unanesthetized and unrestrained. In the present study, we used a barometric chamber to measure steady state HCVR of hamsters with chronic cannulation of their aortas. In 16 hamsters, the mean (+/- SD) of HCVR, defined as changes in ventilation divided by changes in Paco2 (range 53-73 mmHg), was 10.1 +/- 4.9 ml X min-1 X mmHg-1. The rise in ventilation during CO2 inhalation at low concentrations was due to a rise in mean inspiratory flow and tidal volume. As inhaled Pco2 increased, frequency of breathing increased because expiratory time fell progressively. Inspiratory time rose slightly with small increases in inhaled CO2, but returned to baseline values as the concentration of inhaled Pco2 increased. These changes in ventilation and its components appear to resemble those found in the unanesthetized cat and in man, but are somewhat different from those found in the rat. PMID- 3085754 TI - Effect of He-O2 breathing on blood gases and ventilation during exercise in normal man. AB - Temporal changes in ventilation (VI) and arterial blood gases after substitution of helium (He) for nitrogen were studied in normal man during constant load exercises of 14 min duration (30 and 90 W). An abrupt switch of helium for air breathing (protocol 1; 5 subjects), or vice-versa (protocol 2; 4 subjects), was made at the 7th min. Whatever the work loads, the effect of He appeared rapidly: higher values of VI (protocol 1) were observed throughout the 7 min period of He O2 breathing, but were only significant (p less than or equal to 0.05) during the first minute after substitution at 90 W. Reverse pattern was observed in protocol 2. Helium induced alveolar hyperventilation: sustained and significant hypocapnia (p less than or equal to 0.05) was observed during helium breathing. This effect does not seem to be a consequence of pulmonary gas exchange disturbance, in that concomitant Po2 was normal. It is suggested that He could have evoked a reflex which overrode humoral regulation. Significant increase in ventilatory CO2 responses at rest during He-O2 compared to air breathing in seven subjects (p less than or equal to 0.01) seems to confirm this hypothesis. PMID- 3085756 TI - Premature ovarian failure. PMID- 3085758 TI - Vascular permeability responses and the role of prostaglandin E2 in an experimental allergic inflammation of air pouch type in rats. AB - Rats were sensitized with azobenzene arsonate-conjugated acetyl bovine serum albumin. An allergic inflammation was induced in the preformed air pouch in the dorsum of the sensitized rats by injecting the antigen dissolved in a 2% sodium carboxymethyl cellulose solution into the air pouch. Time course changes of vascular permeability, accumulated pouch fluid volume and prostaglandin E2 (PGE2) levels in the pouch fluid were compared in sensitized and non-sensitized rats to characterize the allergic inflammatory reaction. Effects of three cyclo-oxygenase inhibitors (indomethacin, diclofenac sodium and tiaprofenic acid) on vascular permeability and accumulated pouch fluid volume 4 and 24 h after the immunological challenge injection were examined to elucidate a possible role of PGE2 in the inflammatory response. Four h after initiating the allergic reaction, although the level of PGE2 in the pouch fluid reached a high level, the vascular permeability response, measured over the period 3.5-4 h, was not suppressed by treatment with the three cyclo-oxygenase inhibitors and neither was the pouch fluid volume measured over the period 0-4 h. However, vascular permeability and accumulated pouch fluid volume at 24 h were suppressed by the cyclo-oxygenase inhibitors in a dose-dependent manner. These observations suggest that in this model, endogenous PGE2 does not affect oedema formation measured at 4 h. However, oedema formation measured at 24 h may be dependent on PGE2 generation. PMID- 3085757 TI - Bioassay of prostacyclin and endothelium-derived relaxing factor (EDRF) from porcine aortic endothelial cells. AB - A cascade superfusion technique has been developed for the differential bioassay of prostacyclin and endothelium-derived relaxing factor (EDRF) released from porcine aortic endothelial cells cultured on microcarriers, packed into a column and perfused. Bradykinin (Bk; 20-100 nM) released prostacyclin (9.6 +/- 1.5 nM per 10(6) cells; mean +/- s.e.mean, n = 9) and prostaglandin E2 (PGE2; 2.1 +/- 0.6 nM per 10(6) cells) from the column measured by relaxation of strips of bovine coronary artery (BCA) and rabbit mesenteric or coeliac artery, respectively. The presence of these prostanoids in the effluent was confirmed by specific radioimmunoassays. A23187 (500-2000 nM) also released both prostacyclin and PGE2 from the cells. This release was long-lasting and not reproducible. Bk (20-100 nM) and A23187 (30-300 nM) released EDRF from the column. This was detected in a cascade of four rabbit aortic strips (RbA), denuded of endothelium and contracted with U46619 or phenylephrine. The relaxation of the RbA strips caused by EDRF was progressively attenuated down the cascade (half-life less than 7s) and was not affected by indomethacin. EDRF and prostacyclin could be differentially bioassayed in a cascade of alternating RbAs and BCAs as prostacyclin did not relax RbAs and the time delay to the BCAs destroys EDRF. EDRF could be bioassayed on its own when the endothelial cells were treated with indomethacin. 5-Hydroxytryptamine 0.2, noradrenaline 1.0, platelet-activating factor (Paf-acether) 1.0, formylmethionyl-leucyl-phenylalanine 1.0, acetylcholine 0.5, bethanecol 0.5, adenosine diphosphate 0.25 and angiotensin II 0.1 microM did not release either prostanoids or EDRF from the column. PMID- 3085760 TI - Preliminary evidence for gut involvement in the pathogenesis of rheumatoid arthritis? AB - 111Indium leucocyte scans were performed on 26 patients with active rheumatoid arthritis. An abnormal localization of radioactivity was observed in the gut of 12 of these patients, generally in the region of the terminal ileum, caecum and ascending colon. No difference was found in the intake of nonsteroidal anti inflammatory drugs between those with positive and negative scans. Two patients with positive scans were on no medication. These observations suggest the possibility of a primary role for a gastrointestinal lesion in the aetiology of rheumatoid arthritis, although these abnormalities could be secondary or unrelated. PMID- 3085759 TI - Changes in the behavioural response to a TRH analogue following chronic amitriptyline treatment and repeated electroconvulsive shock in the rat. AB - The arousal elicited in rats by injection into the nucleus accumbens of the thyrotrophin-releasing hormone analogue CG 3509 (orotyl-histidyl-prolineamide) was used to assess the responsiveness to thyrotrophin-releasing hormone following repeated treatment with amitriptyline or electroconvulsive shock. Fourteen day administration of amitriptyline (15 mg kg-1 i.p. twice daily) reduced the behavioural response to bilateral intra-accumbens injection of CG 3509 (2 X 2.5 micrograms). CG 3509-induced hyperactivity, recovery from pentobarbitone-induced anaesthesia and the reversal of both pentobarbitone-induced hypothermia and decreased respiration, were all significantly reduced compared to either the response of the animals prior to amitriptyline administration or that observed in rats following chronic saline administration. Repeated administration of electroconvulsive shock (5 shocks over 10 days) significantly increased CG 3509 induced hyperactivity and the degree of reversal of pentobarbitone-induced hypothermia and respiratory depression following CG 3509 administration. The results demonstrate that chronic antidepressant treatments alter the central functional responsiveness to thyrotrophin-releasing hormone. These changes are discussed with respect to the effects of antidepressant treatments on 5 hydroxytryptamine receptors and possible thyrotrophin-releasing hormone- aminergic interactions. PMID- 3085761 TI - Small intestine ultrastructural changes and auranofin treatment in rheumatoid arthritis. PMID- 3085762 TI - What should we do about work related cancer? PMID- 3085763 TI - IVF update. PMID- 3085764 TI - Pseudo-obstruction. PMID- 3085765 TI - Primary health care: an evolutionary agenda. PMID- 3085766 TI - Do asthmatics suffer bronchoconstriction during rapid eye movement sleep? AB - Many patients with asthma are troubled by nocturnal wheeze. The cause of this symptom is unknown, but sleep is an important factor. A study was carried out to determine whether nocturnal bronchoconstriction is related to any specific stage of sleep. Eight asthmatics with nocturnal wheeze and eight control subjects performed forced expiratory manoeuvres immediately after being woken from rapid eye movement (REM) or non-REM sleep, wakings being timed to differentiate temporal effects from those related to the stage of sleep. The control subjects showed no significant temporal bronchoconstriction or bronchoconstriction related to the stage of sleep. All patients showed bronchoconstriction overnight, the mean peak expiratory flow rate falling from 410 (SEM 50) 1/min before sleep to 186 (49)1/min after sleep. After the patients had been woken from REM sleep the forced expiratory volume in one second was on average 300 ml lower (p less than 0.02) and peak expiratory flow rate 45 1/min lower (p less than 0.03) than after they had been woken from non-REM sleep. As wakenings from REM sleep were 21(8) minutes later in the night than those from non-REM sleep multivariate analysis was performed to differentiate temporal effects from those related to the stage of sleep. This showed that the overnight decreases in forced expiratory volume in one second and peak expiratory flow rate were significantly related both to time and to REM sleep. This study suggests that asthmatics may suffer bronchoconstriction during REM sleep. PMID- 3085767 TI - Impact of maternal postnatal depression on cognitive development of young children. AB - Ninety four women and their first born children took part in a longitudinal study of maternal mental health during pregnancy and after delivery. The children's cognitive functioning was assessed at age 4 using the McCarthy scales, without knowledge of the mothers' psychiatric history or current health. As expected girls performed slightly better than boys and children from middle class and professional families did better than children from working class homes, as did children whose mothers had achieved at least one A level at school. Significant intellectual deficits were found in the children whose mothers had suffered with depression, but only when this depression occurred in the first year of the child's life. Marital conflict and a history of paternal psychiatric problems were independently linked with lower cognitive test scores; together with a working class home background these were the only factors that contributed to the deleterious effect of maternal postnatal depression. PMID- 3085768 TI - Alleviation of jet lag by melatonin: preliminary results of controlled double blind trial. PMID- 3085769 TI - Carbamazepine neurotoxicity precipitated by diltiazem. PMID- 3085770 TI - Aqueous malathion 0.5% as a scabicide: clinical trial. PMID- 3085771 TI - Deprivation and health in one general practice. AB - A detailed comparison made in late 1984 of 587 matched pairs of patients from neighbouring deprived and more endowed urban communities, both served by the same experienced primary health care team, showed much worse morbidity, with almost three times as much mental illness, in the deprived group. This group also had 60% more hospital admissions and 75% more casualty attendances. In contrast, they had a much lower uptake of preventive health care, especially childhood immunisations and cervical cytology in older women. A much higher birthrate within the deprived group, contributing to ill health by worsening overcrowding and deprivation, indicates that family planning is ineffective where it is most needed. Practical measures have now been instituted to improve the preventive care of the deprived community. PMID- 3085772 TI - Levels and sources of stress in medical students. AB - Levels of stress, as measured by the general health questionnaire, were assessed in 318 medical students in their fourth year at three British universities. Mean scores were higher than those in other groups within the general population, and the estimated prevalence of emotional disturbance was 31.2%, a proportion similar to that reported in medical students in the United States. There were no differences in prevalence or in mean scores of stress between the sexes. Twelve (4%) students reported high intake of alcohol, and almost half of the students had increased their intake in the past two years. The four categories most commonly cited in answers to an open ended question on recent stressful events were talking to psychiatric patients, effects on personal life, presenting cases, and dealing with death and suffering. Relationships with consultants raised the strongest negative feelings, with 102 (34%) students finding these particularly stressful. Stress among medical students should be acknowledged and attempts made to alleviate it. PMID- 3085773 TI - The Mandwa experiment, an alternative strategy. PMID- 3085774 TI - Immunisation of preterm infants. PMID- 3085775 TI - Acute adrenal crisis precipitated by thyroxine. PMID- 3085776 TI - ABC of resuscitation. Advanced life support in general practice. PMID- 3085778 TI - Technology assessment in Britain: lessons from the lithotripter. PMID- 3085777 TI - Non-steroidal anti-inflammatory drugs and serious gastrointestinal adverse reactions--2. PMID- 3085779 TI - High density lipoprotein cholesterol is not a major risk factor for ischaemic heart disease in British men. PMID- 3085780 TI - Drugs for poor sleepers? PMID- 3085781 TI - Awareness of Skoal Bandits. PMID- 3085782 TI - Epidemic of AIDS related virus infection among intravenous drug abusers. PMID- 3085784 TI - Role of drugs in fractures of the femoral neck. PMID- 3085783 TI - Risk of AIDS to health care workers. PMID- 3085785 TI - Dyspepsia: incidence of non-ulcer dyspepsia in a controlled trial of ranitidine. PMID- 3085786 TI - Code of practice for the Mental Health Act 1983. "Patronising and unrealistic". PMID- 3085787 TI - Code of practice for the Mental Health Act 1983. Codifying care. PMID- 3085788 TI - Ethylene oxide and anaphylaxis during haemodialysis. PMID- 3085789 TI - Osteomalacia in Paget's disease treated with short term, high dose sodium etidronate. AB - Eleven patients with Paget's disease treated with sodium etidronate 20 mg/kg/day for two and four weeks showed significant reductions in plasma alkaline phosphatase activity and urinary hydroxyproline excretion, both of which are biochemical markers of bone turnover. After four weeks of treatment, however, histological examination of iliac crest biopsy samples showed that despite a rapid reduction in bone resorption there was an appreciable mineralisation defect; even after only two weeks' treatment the abnormalities in bone formation persisted for up to 10 weeks. The adverse effects of sodium etidronate on mineralisation cannot be dissociated from its beneficial effect on resorption even when it is given for short periods. PMID- 3085790 TI - Deficiency of thiosulphate sulphurtransferase (rhodanese) in Leber's hereditary optic neuropathy. AB - Leber's hereditary optic neuropathy is a rare cause of progressive visual failure. Its cause is unknown, but one hypothesis is that patients have a defect in the detoxication of cyanide. One of the enzymes used in this detoxication is thiosulphate sulphurtransferase (rhodanese). The activity of this enzyme was measured in the rectal mucosa of a group of subjects with Leber's hereditary optic neuropathy, and it was found to be considerably reduced compared with that in a group of controls (p less than 0.001). This finding supports the hypothesis of an inborn error of cyanide detoxication in this condition. PMID- 3085792 TI - Cytological brush entrapment: a hazard in the stomach postoperatively. PMID- 3085791 TI - Food allergy or intolerance in severe recurrent aphthous ulceration of the mouth. PMID- 3085793 TI - Broken necks in passengers in London taxi accidents. PMID- 3085794 TI - Deficient urinary fibrinolysis in renal stone disease. PMID- 3085795 TI - Aneurysm presenting as a breast mass. PMID- 3085796 TI - General practitioner referrals to a clinical child psychologist. AB - An analysis of the problems that are referred by general practitioners to a clinical child psychologist working in the community is presented. To illustrate some of the principles of assessment and management an example from each of three main categories--behaviour problems, emotional disturbances, and disorders of function--is given. PMID- 3085797 TI - Prevention for patients over 75: is it worth the bother? AB - This paper describes the way in which one primary care team interpreted the evidence about screening and case finding in old age and introduced a simple system to test its feasibility. From the results of the study, which was conducted by members of the team without help from research workers, the team concluded that contact should be established with every person over the age of 75 every year but that it would continue to concentrate on managing problems known to it rather than searching for asymptomatic or unreported problems. PMID- 3085799 TI - Court of appeal to rule on Brightlingsea dispute over restrictive covenant. PMID- 3085798 TI - Identification of emotional problems in postpartum women by health visitors. AB - One hundred mothers of babies aged under 15 weeks who attended well baby clinics were rated for the presence of emotional disorders by health visitors. These assessments were compared with the mothers' scores on the General Health Questionnaire (GHQ), a screening instrument for identifying psychiatric cases in the general population. The results indicate that symptoms of minor psychiatric disorder are a problem for an appreciable number of postpartum women, although the health visitors showed a misclassification rate of roughly 40%. It is suggested that routine screening using the questionnaire at the time of the baby's six week check would both improve the detection rate and also enable the health visitors to give extra support to those mothers who were most in need of it. PMID- 3085800 TI - The Mental Health Act Commission's "guidelines": a further threat to psychiatric research. PMID- 3085801 TI - Elderly patients in acute medical wards: factors predicting length of stay in hospital. AB - A prospective study of 419 patients aged 70 and over admitted to acute medical wards was carried out by medical staff from a geriatric unit. Data, including presenting problem, housing, social support, mental state, continence, and degree of independence before and after admission, were recorded. Of the 419 patients, 143 remained in hospital after 14 days and 65 after 28 days. The major factors associated with prolonged stay in hospital included advanced age, stroke, confusion and falls as reasons for admission to hospital, incontinence, and loss of independence for everyday activities. Social circumstances did not predict length of stay. Although these factors are interrelated, the most important influence on length of stay was the medical reason for admission. Early contact with the geriatric medical unit in these patients may speed up the recovery or result in more appropriate placement. PMID- 3085802 TI - Bed blocking in Bromley. AB - A point prevalence survey of all acute beds in the Bromley district found that more than one in 10 patients were classified by their doctors as bed blockers (one in five in the medical wards). There were appreciable clinical and demographic differences distinguishing bed blockers from patients whose stay had been prolonged and who were judged as still requiring acute beds. Social and administrative problems also contributed to bed blocking so that further action by geriatricians, psychogeriatricians, and social workers was required to reduce the numbers. A substantial proportion of bed blockers, however, were highly dependent and could be transferred only to long stay wards or nursing homes. Bed blocking seems inevitable in wards that are attempting to cope with the steadily increasing proportion of elderly patients according to traditional models of acute care. PMID- 3085803 TI - ABC of resuscitation. Resuscitation by ambulance crews. PMID- 3085804 TI - The law tries to decide whether whooping cough vaccine causes brain damage: Professor Gordon Stewart gives evidence. PMID- 3085805 TI - Missed malignant melanoma. PMID- 3085806 TI - Combined use of vasopressin and synthetic hypothalamic releasing factors as test of anterior pituitary function. PMID- 3085807 TI - Hypomagnesaemic tetany associated with prolonged treatment with aminoglycosides. PMID- 3085808 TI - Asymptomatic microscopical haematuria. PMID- 3085809 TI - Renal handling of calcium and sodium in metastatic and non-metastatic malignancy. PMID- 3085810 TI - Treatment of type II diabetes. PMID- 3085811 TI - So what will fibrinolytic therapy offer your patients with myocardial infarction? PMID- 3085813 TI - Ampoules, infusions and filters. PMID- 3085812 TI - Toxicity of vitamins. PMID- 3085814 TI - Reaction to food additives. PMID- 3085815 TI - Tumour markers in germ cell tumours. PMID- 3085816 TI - Manpower: compendium of deliberate mistakes. PMID- 3085817 TI - Bed numbers and good medical education. PMID- 3085818 TI - Systemic steroids in chronic severe asthma. PMID- 3085819 TI - Electrophysiological testing after acute myocardial infarction. PMID- 3085821 TI - Incompetence in medical practice. PMID- 3085820 TI - Hearing and memory in anaesthetised patients. PMID- 3085823 TI - Mortality probability in victims of fire trauma: revised equation to include inhalation injury. AB - There are no clear guidelines on the early diagnosis of injury due to inhalation of smoke. A clinical scoring system in the form of a previously prepared questionnaire may be used in the accident and emergency department by staff who are inexperienced in the management of inhalation injury. By quantifying injury due to smoke inhalation, its contribution to mortality in a large group of fire victims was established and a revised mortality probability equation derived using age, percentage surface area of the burn, and extent of inhalation injury. This mortality probability equation may be used to divide patients into risk categories for early intensive care management and allows the comparison of mortality data between accident and emergency units receiving varying numbers of patients with injuries due to burns and smoke inhalation. PMID- 3085822 TI - Mortality from and incidence of stroke in Stockholm. AB - To study trends in the incidence of and mortality from stroke in Stockholm during 1974-81 all cases (n = 56566) of stroke in patients aged over 40 were identified from the Swedish Cause of Death Register and the Inpatient Care Register. Information on the population at risk was obtained from the civil registration system. A multiplicative model was used to control for changes in the distribution of age during the study. Mortality from stroke decreased annually throughout the study by a mean of 2.3% for men and 3.5% for women. This favourable development was not accompanied by a similar decrease in the incidence of stroke. In men the total incidence (including recurrent strokes) and incidence of first stroke increased continuously. In women the total incidence showed virtually no change, whereas the incidence of first stroke decreased somewhat. These findings, in addition to an expected shift of age profile in the population towards more elderly people, should be considered in the planning of future health care resources. PMID- 3085824 TI - Screening for scoliosis: the problem of arm length. PMID- 3085825 TI - Rape: the forgotten victim. PMID- 3085826 TI - General practitioners' retirement plans and what influences them. AB - The results of a study of the attitudes of 197 general practitioners aged 55 and over towards retirement and their plans for retirement are reported. Few wished to retire very early, and only a further 40% definitely planned a clean break from practice. Nearly half planned on taking "24 hour retirement," even though most (78%) will be entitled to full pension rights. Job satisfaction and health were the most important factors influencing the timing of the retirement. Seventy seven per cent thought that there should be no formal retirement policy, 79% wanted no compulsory retirement age, and 80% wanted no further controls or safeguards directed at older practising general practitioners. Half of the general practitioners in the sample were not looking forward to retirement. Personal discussions with respondents aged 65 and over suggested that there are many older general practitioners who plan to practise for some time, who feel that they will know when the time has come to stop, but who often express the hope that they may "die in harness." A large proportion of older doctors are in single-handed practice. In view of this, and also of the evidence from North America which suggests that older doctors may practise inferior medicine, it is thought that the ability of such general practitioners to evaluate their competence should be studied by methods such as peer assessment techniques. PMID- 3085827 TI - How elderly patients with femoral fracture develop pressure sores in hospital. AB - The routine hospital management of 100 consecutive elderly patients was studied to determine the reason for the high incidence of pressure sores among patients admitted to hospital for femoral fractures. Of these patients, 66 developed sores, 83% occurring by the fifth day in hospital. This was due to the long periods that patients were immobilised on high pressure surfaces in the casualty department, wards, and theatres before repair of the fracture and restoration of their weight bearing function. Sores are not simply a ward or nursing problem, but an unintended consequence of hospital treatment. To reduce the incidence of sores elderly patients should be treated on low pressure patient support systems from the point of entry to hospital until mobility is restored. PMID- 3085828 TI - The doctor, the patient, and their contract. I. The general practitioner's contract: why change it? PMID- 3085829 TI - ABC of resuscitation. Resuscitation in the accident and emergency department. PMID- 3085830 TI - Hypoglycaemia and antimalarial drugs: quinidine and release of insulin. AB - Life threatening hypoglycaemia has been closely associated with the use of quinine, but the effect of quinidine and the synthetic antimalarials on the homoeostasis of glucose has not been investigated. In volunteers given a fixed dose of 500 mg base and patients with malaria given a quinidine loading dose (15 mg base/kg) mean (SEM) plasma insulin concentrations rose from 6.1 (1.5) mU/l to 10.9 (4.4) mU/l (p less than 0.02) and 10.4 (2.0) mU/l to 18.5 (5.3) mU/l (p less than 0.04), respectively. Plasma glucose concentrations fell from 4.5 (1.1) mmol/l (81 (20) mg/100 ml) to 4.0 (0.3) mmol/l (72 (5) mg/100 ml) in volunteers (p less than 0.04) and from 5.7 (1.3) mmol/l (102 (23) mg/100 ml) to 4.8 (1.6) mmol/l (86 (29) mg/100 ml) in patients (p less than 0.05). One of two patients with cerebral malaria and acute renal failure became profoundly hypoglycaemic (plasma glucose concentration 1.4 mmol/l (25 mg/100 ml), plasma insulin concentration 3.1 mU/l). Hypoglycaemia may occur in any severely ill fasting patient given parenteral quinidine. The other antimalarials tested, chloroquine, amodiaquine, mefloquine, and halofantrine, did not stimulate the release of insulin, an important advantage that should be taken into account when treatment is chosen for Plasmodium falciparum malaria. PMID- 3085831 TI - Leptospirosis in man, British Isles: 1984. PMID- 3085832 TI - Motor neurone disease presenting as respiratory failure. PMID- 3085833 TI - Stones, lithotripters, trials, and arguments. PMID- 3085834 TI - Happiness is: iron. PMID- 3085835 TI - Glucocorticoid receptors in depression. PMID- 3085836 TI - Impotence: science and sciencibility. PMID- 3085837 TI - Role of drugs in fractures of the femoral neck. PMID- 3085839 TI - Vegetable consumption and acute appendicitis. PMID- 3085840 TI - Pressure of research on junior staff. PMID- 3085838 TI - Recurrence of focal glomerulosclerosis despite cyclosporin treatment after renal transplantation. PMID- 3085841 TI - Drugs in developing countries: inching towards rational policies. PMID- 3085842 TI - Progress towards a new pertussis vaccine. PMID- 3085843 TI - Mouth to mask respiration. PMID- 3085845 TI - High altitude haemofiltration. AB - Evacuating people in acute renal failure by air is difficult because the hazards of fluid overload and anaemia are potentiated by altitude. In two such patients continuous arteriovenous haemofiltration was used to control their fluid problems during aeromedical evacuation. In the first case, a patient with renal failure and blast lung, haemofiltration was performed at 500 ml/h over a four hour journey; in the second, a woman with severe pre-eclamptic toxaemia who developed acute renal failure after caesarean section, haemofiltration was performed at 200 ml/h over a 14 hour flight. Both patients recovered fully. In these two cases haemofiltration permitted control of the intravascular volume during aeromedical evacuation. The technique represents a major advance in the safe transfer of casualties. PMID- 3085846 TI - Are families of diabetic children adequately taught? PMID- 3085844 TI - Diuretic treatment in decompensated cirrhosis and congestive heart failure: effect of posture. AB - The diuretic effect of the supine position was evaluated in six patients with cirrhosis and ascites and six with congestive cardiac failure. After fasting overnight in bed the patients received bumetanide 1 mg intravenously and were then immediately randomly assigned to either bed rest in the supine position or normal daily activity in the upright position for the next six hours. Two days later the procedure was repeated, the patients being assigned to the other posture. The diuretic response was similar in patients with heart failure and cirrhosis, and was significantly greater in the supine than in the upright position: mean 1133 v 626 ml/6 h (p less than 0.01). The natriuresis was similarly larger during recumbency: mean sodium 96 v 45 mmol(mEq)/6h (p less than 0.01), and the excreted potassium in six hours was similar in both postures. The glomerular filtration rate was 100 and 66 ml/min (p less than 0.01) and heart rate 76 and 83 beats/min (p less than 0.01) in the supine and upright positions respectively. Plasma concentrations of noradrenaline, renin, and aldosterone were all raised even when the patient adopted the supine position, and a further significant rise was observed during the upright position. The results suggest that the attenuated response to intravenous bumetanide in the upright position and during normal daily activity may be due to the activation of several homeostatic mechanisms that may reduce the excretion of water and salt. PMID- 3085847 TI - Localised intratesticular abscess complicating epididymo-orchitis: the use of scrotal ultrasonography in diagnosis and management. PMID- 3085848 TI - Occupational asthma due to methyl methacrylate in an orthopaedic theatre sister. PMID- 3085849 TI - Polyarthropathy associated with Cushing's disease. PMID- 3085851 TI - Prescribing information to patients. PMID- 3085850 TI - Do general practitioners "miss" depression in elderly patients? AB - In a study of the prevalence of depression in 235 elderly patients who attended general practice surgeries less than 12% of the disagreement between the research assessment of depression and the general practitioner's assessment was due to "missed" depression. There were, however, low rates of referral and of treatment with antidepressant drugs. If these findings are confirmed the study of the management and outcome of depression in such patients may be more rewarding than attempts to improve the recognition of depression. PMID- 3085852 TI - Why are patients with acute stroke admitted to hospital? AB - Data on 515 consecutive patients registered with the Oxfordshire Community Stroke Project were used to compare the characteristics of those patients who were admitted to hospital within one month after their first stroke with those who remained in the community during that time. Twenty eight patients had their stroke while in hospital for other conditions, and of the remaining 487, 266 were admitted. Though patients with a severe neurological deficit were significantly more likely to be admitted, 47 out of 202 such patients were managed in the community. In a substudy of 162 consecutive patients the general practitioners' reasons for either arranging admission to hospital or continuing with community care in the first week after the stroke were ascertained. Sixty patients were admitted. The only reason for admission was diagnostic uncertainty in five cases (though this was a contributing factor in 25) and to provide nursing or general, non-medical care in 25. Patients who lived alone were more likely to be admitted. All 12 patients who presented directly to the casualty department were admitted, though only five had had a severe stroke. A stroke service that provides a facility for rapid outpatient and domiciliary diagnosis as well as a rapidly acting domiciliary nursing team might reduce the number of patients with stroke admitted to hospital without adversely affecting the quality of patient care: this should be properly evaluated. PMID- 3085853 TI - Randomised trials and informed consent in neonatal medicine. PMID- 3085854 TI - The doctor, the patient, and their contract. II. A good practice allowance: is it feasible? PMID- 3085855 TI - ABC of resuscitation. Resuscitation in hospital. PMID- 3085856 TI - Gastrointestinal investigation of iron deficiency anaemia. PMID- 3085857 TI - Healthy living on the "Islands of Love". PMID- 3085858 TI - Akathisia--or not sitting. PMID- 3085859 TI - Effects of indomethacin and sulindac on blood pressure of hypertensive patients. PMID- 3085860 TI - Sexual abuse of children. PMID- 3085861 TI - Occurrence of polymyalgia rheumatica in rheumatoid arthritis. PMID- 3085862 TI - Amphotericin B, aminoglycosides, and hypomagnesaemic tetany. PMID- 3085863 TI - On line prescribing by computer. PMID- 3085864 TI - Haemoglobin concentration and linear cardiac output, peripheral resistance, and oxygen transport. PMID- 3085865 TI - Asystole and electromechanical dissociation. PMID- 3085866 TI - Cellular localization of adrenergic receptors in rat and human brain. AB - The localization of adrenergic receptors in the central nervous system was studied in two physiological conditions of noradrenergic denervation, a 6 hydroxydopamine-induced lesion of the locus coeruleus in newborn rat, and a pathological related degeneration of the locus coeruleus in man, Parkinson's disease. The localization of these receptors in the synapse has been studied with the technique of subcellular fractionation by differential centrifugation. In lesioned rats, an increase in the density of alpha 1 and beta 1 receptors was observed in several brain regions, in contrast to alpha 2 receptors which were not modified. Subcellular fractionation in lesioned rats showed an increase in alpha 1 and beta 1 receptors in synaptosomal fractions. Similar results were found in parkinsonian patients: alpha 1 receptors increased in the synaptosomal fraction; beta receptors increased in synaptosomal and microsomal fractions. These results suggest that alpha 1 and beta 1 receptors may be located on non noradrenergic nerve terminals in mammalian brain. alpha 2 and beta 2 receptors may be situated on glial cells or neuronal elements unrelated to noradrenergic input. PMID- 3085867 TI - Light and electron microscopic immunocytochemistry of GRF-like immunoreactive neurons and terminals in the rat hypothalamic arcuate nucleus and median eminence. AB - Growth hormone-releasing factor (GRF) synthesizing neuronal perikarya and terminals were investigated by light and electron microscopic immunocytochemistry using rat hypothalamus. Immunoreactive neuronal perikarya were located mainly in the ventrolateral part of the arcuate nucleus. They contained well developed cell organella such as mitochondria and rough surfaced endoplasmic reticulum with some expansion. They also contained immunoreactive dense granules (80-120 nm in diameter). On the surface of the immunoreactive neuronal perikarya were frequently found non-immunoreactive axo-somatic synapses. Therefore, the GRF-like immunoreactive neurons were assumed to receive neuronal inputs from other neurons on their neuronal soma. In the external layer of the median eminence large numbers of immunoreactive terminals were distributed particularly around the capillaries of the portal vessel. Electron microscopic immunocytochemistry revealed large numbers of immunoreactive terminals containing immunoreactive dense granules, synaptic vesicles and mitochondria in the vicinity of the basement membrane of the pericapillary space of the portal vessel. Therefore, we concluded that GRF-like immunoreactive substances are released into the portal capillaries from the nerve terminals, which originate from the neuronal perikarya in the ventrolateral part of the arcuate nucleus, and act on growth hormone release in the anterior pituitary. We also suggest that GRF-like immunoreactive neurons have abundant terminal arborization in the external layer of the median eminence. PMID- 3085868 TI - An intragastric meal releases the putative satiety factor cholecystokinin from hypothalamic neurons in cats. AB - The release of cholecystokinin-like immunoreactivity (CCK-LI) from feline hypothalamus was studied in relation to a meal by use of the push-pull perfusion technique. While levels of CCK-LI in the perfusate of overnight-fasted anesthetized cats were below assay sensitivity (less than 7 pg/30 min), intragastric administration of a carbohydrate-amino acid meal elicited a 3-fold increase in CCK-LI, identified by high-performance liquid chromatography as the C terminal octapeptide of CCK (CCK-8). Examination of an extrahypothalamic site showed no comparable release in CCK-LI. Intravenous infusions of CCK-8 at doses imitating physiological blood levels up to 400 times higher than those seen after physiological stimulation demonstrated the existence of a CCK blood-brain barrier in the lateral hypothalamus. These observations provide support that CCK may play a physiological role in termination of feeding behavior. PMID- 3085869 TI - Unilateral peri-substantia nigra catecholaminergic lesion and amygdala kindling. AB - Recent evidence suggests that the substantia nigra (SN) may be involved in the modulation of kindled seizures in adult rats. In this report we investigated the role of the dopaminergic nigrostriatal pathway in mediating the SN effect on seizures by lesioning this pathway with unilateral infusions of 6-hydroxydopamine (6-OHDA) in the vicinity of the right SN with or without desmethylimipramine pretreatment. Our data suggest that the facilitation of amygdala kindling observed following 6-OHDA lesion in the vicinity of the ipsilateral SN is due to norepinephrine depletion of the ipsilateral forebrain. Selective destruction of the nigrostriatal dopaminergic neurons neither facilitates nor inhibits the development of amygdala-kindled convulsions in adult rats. PMID- 3085870 TI - Regulation of galactocerebroside and sulfatide synthesis by hormones in chick neural cultures. AB - Chick neural cultures were used to study effects of insulin, thyrotropin releasing hormone, growth hormone and glucagon on myelin lipid synthesis in vitro. The incorporation of [3H]galactose into myelin associated lipids such as cerebroside and sulfatide was used as an index for various hormonal effects on myelination. The data suggest that these hormones were effective on myelin lipid synthesis only in the central nervous cells, not in the peripheral nerve cells. PMID- 3085871 TI - An important role of the central amygdaloid nucleus and mammillary body in the mediation of conflict behavior in rats. AB - The present study was designed to elucidate the functional role of central amygdaloid nucleus (ACE) and mammillary body (MB) in the mediation of behavioral suppression using rat conflict punishment procedure. Lesion of ACE produced a significant and long-lasting increase in the punished responding during the experimental period. Rats with lesion of MB also showed a significant increase in the punished response 10-14 days after brain lesioning. These results demonstrated the important role of ACE and MB in the mediation of behavioral suppression such as conflict behavior. PMID- 3085872 TI - Effects of neonatal administration of monosodium glutamate on plasma growth hormone (GH) response to GH-releasing factor in adult male and female rats. AB - Female and male rats were treated with monosodium glutamate (MSG; 4 mg/g b. wt.) as neonates and the capability of the pituitary gland to secrete growth hormone (GH) in response to an intravenous injection of human GH-releasing factor (GRF) was evaluated under pentobarbital anesthesia on 109 days of life. Immunoreactive GRF content in the pituitary stalk-median eminence tissue in MSG-treated rats was less than 20% of that of control. A significant dose-dependent plasma GH response was observed after the administration of two doses of human GRF (0.25 and 1 microgram/kg b. wt., i.v.) in both control and MSG-treated rats. The responses between MSG-treated and control rats were comparable in female rats, but they were significantly reduced in male MSG-treated rats. These results show that the pituitary's responsiveness to exogenous GRF is well preserved in MSG-treated rats despite prolonged and severe depletion of endogenous GRF and there exists a sex difference in the effect of MSG on GH secretion elicited by GRF. PMID- 3085873 TI - Stimulation by gastrin-releasing peptide, neurotensin and DN1417, a novel TRH analog, of dopamine and norepinephrine release from perifused rat hypothalamic fragments in vitro. AB - Both dopamine (DA) and norepinephrine (NE) release from perifused rat hypothalamic fragments was increased by depolarizing concentrations of potassium (K+, 20 mM and 56 mM) in a dose-related and Ca2+-dependent manner. DA and NE release induced by high K+ (20 mM) was further enhanced by gastrin-releasing peptide (GRP, 10(-5)-10(-6) M) and DN 1417 (10(-5) M), a thyrotropin-releasing hormone (TRH) analog. GRP (10(-5) M), neurotensin (NT, 10(-5) M) and DN 1417 (10( 5) M) also stimulated spontaneous release of DA and NE from the hypothalamus. These results suggest that GRP, NT and DN 1417 act at the hypothalamic catecholamine nerve terminals and stimulate the release of DA and NE in the rat. PMID- 3085874 TI - Pregnancies and menstrual function before and after combined radiation (RT) and chemotherapy (TVPP) for Hodgkin's disease. AB - The menstrual cycle, pregnancies, and offspring were evaluated before and after initial combined radiation (RT) and chemotherapy with thiotepa, vinblastine, vincristine, procarbazine, and prednisone (TVPP), in 34 women between the ages of 18 and 44 (median 26.5 years) treated for Stage II and Stage III Hodgkin's disease. The median range of follow-up is 83.1 months (range 40.5-140). After therapy 94.1% (32/34) continued to menstruate. Two of the four patients over the age of 35 ceased to menstruate. All patients under the age of 35 continued to menstruate (30/30). Age at the time of diagnosis was the only factor affecting change in menses with a significant probability (p = .001) that women greater than 30 years of age will experience some change in menstrual pattern. Seventeen pregnancies occurred in 12 women after therapy; 2 had 4 elective abortions; 10 delivered 12 children with normal physical development; 1 will deliver six months from now. Twelve of thirteen patients who wanted to become pregnant have conceived. The ability to become pregnant and deliver normal children after intensive treatment with combined radiation and chemotherapy (RT/TVPP) was comparable to the patients' pretreatment record. PMID- 3085875 TI - [Proposal for a new synthetic inhibitor of C1 esterase, methyl-2 thiazoline carbamic ester-3 spirobutenolide: enzyme and electron studies]. AB - The correlation obtained between the electronic properties and the in vitro inhibiting effect on C1 esterase of synthetic derivatives from spirobutenolides series, lead to a synthetic compound. The molecule is especially hopeful in this enzymatic activity and so comparable to the natural inhibitor. PMID- 3085876 TI - [Induced maternal behavior in the domestic hen. Influence of partial or total separation on the maintenance of maternal responsiveness]. AB - The influence of direct physical contact on maintaining maternal responsiveness in induced adult hens was investigated using a separation procedure. Partial separation from chicks causes a significant decline of the clucking rate in hens, this response however does not disappear as in the case of total separation. The possibility for physical contact between hen and chicks contributes largely, but not uniquely, to maintain maternal responsiveness in the domestic hen. PMID- 3085877 TI - [Translocation t(1; 14) and rearrangement of the gene for the alpha chain of the T-cell receptor in acute T-lymphoblastic leukemia]. AB - A t(1; 14) (p32; q11) translocation has been found by the cytogenetic study of a T cell acute lymphoblastic leukemia patient. Molecular hybridization with a probe (D14S7) which recognizes a fragment of the alpha chain T receptor gene has shown a rearranged EcoRI 11.0 kb band in addition to the germline 3 and 8 kb bands. This translocation infrequently described until now is a new example of an alpha chain gene rearrangement in T cell malignancy. Moreover the breakpoint on chromosome 1 may also involve the newly isolated protooncogene, L-myc, normally localized on the chromosomal band 1 p32. PMID- 3085878 TI - [Protective effect of trehalose dimycolate in infestation of mice by Trypanosoma musculi]. AB - Trehalose dimycolate (TDM) treated and untreated mice were infected with Trypanosoma musculi. Compared to untreated mice, treated mice exhibited a five fold reduced number of circulating parasites. Untreated infected mice had a splenomegaly but only a slight increase of spleen weight of treated mice was observed. The role of trehalose dimycolate on T. musculi infection, especially via the macrophage is discussed. PMID- 3085879 TI - [Antagonistic effects of acetylcholine and caffeine on the contractility of the auricular myocardium of rats]. AB - In the rat atrium, the contraction rebound occurring after ACh treatment could not be related to an increase in action potential duration and disappeared in the presence of atropine or caffeine. Contractures elicited by caffeine (10 and 20 mM) were inhibited by ACh. This inhibition was suppressed by atropine. The hypothesis that ACh could increase the sarcoplasmic reticulum Ca diastolic reuptake is discussed. PMID- 3085880 TI - [The metaphase chromosome: functional inertia and ability related to the presence of sequences of single-stranded DNA]. AB - Isolated metaphase chromosomes from KB cells were used as template in an in vitro DNA synthesis assay. In these conditions, no synthesis was noticed, confirming template inactivity of isolated metaphase chromosomes. DNA synthesis was noticed after a pretreatment with either methanol-acetic acid or RNase A. Analysis of in vitro synthesized polydeoxyribonucleotides showed two fractions of 4 S and 7-8 S. These results suggest the presence in metaphase chromosome of single stranded DNA sequences. Such sequences are shown in DNA extracted from chromosomes. They would preexist in this organelle and would be unmasked by the treatments that restore template activity of metaphase chromosome. PMID- 3085881 TI - [A new promotor of nerve growth: naftidrofuryl]. AB - 20 day-old rat thoracic dorsal root ganglia were grown for 48 hrs. in Iscove's medium supplemented with 8% fetal calf serum and 600 mg/100 ml glucose. Naftidrofuryl was added at 10(-6), 10(-7), 10(-8) and 10(-9) M concentrations to the culture medium. The 10(-7) and 10(-8) M concentrations induced a statistically significant increase of the number (30 to 40%; p = .0054 and .0016, respectively) and length (20 to 30%; p = .0012 and .001, respectively) of neurites of the outgrowth measured after Bodian's protargol impregnation. The width of the cell spread in the outgrowth was also enlarged at the 10(-7) and 10( 8) M concentrations (18 to 26%; p = .0012; p less than .0001, respectively). PMID- 3085882 TI - [Chronoavailability: a theoretical method of studying chronopharmacology]. AB - The optimum time of drug administration or the chronestesy of a biosystem can be theoretically determined by the integration of the function: (drug concentration) (susceptibility of the biosystem) versus time. This integral called chronoavailability could be useful to design experiments for evaluation of chronopharmacologic effects in man. PMID- 3085883 TI - [Demonstration of the intracellular accumulation of intermediary fluorescent metabolites of various polycyclic aromatic hydrocarbons by resolution of the fluorescence spectra of isolated living cells]. AB - Using microspectrofluorimetry, we have studied some spectral modifications induced by the accumulation of fluorescent metabolites from some PAH in single living cells (3T3 and RTG2 fibroblasts). Whatever the parent compound under study, no spectral deformation has been detected in the 3T3 cells. On the contrary, the characteristic fluorescence spectra were strongly modified in RTG2 cells when the parent compound was either B(a)P or CPAP. The B(a)P metabolites have been identified as 3-OH-B(a)P and 9-OH-B(a)P. PMID- 3085884 TI - [Antigenic study of the differentiation of the human kidney using monoclonal antibodies]. AB - The production of monoclonal antibodies against human embryonic renal cells allowed to display on the adult human kidney some antigens typical of certain structures or tissues: the proximal convoluted tubule for EG 9-11 and EG 19-6 monoclonal antibodies, the glomerular basement membrane for EG 14-1, the urothelium for EE 24-6, the connective tissue for EK 8-1 and EK 17-1 and probably the capsular and tubular basement membranes for EK 8-1. Simultaneously, we could follow the spatial and temporal repartition of the antigens during the renal development. One of them (EI 16-1) seemed to disappear in the adult and might correspond to a foetal type-antigen. PMID- 3085885 TI - [Demonstration of the heterogeneity of the intracellular activity of oxidases by quantitative microspectrofluorimetry: comparison of two cell strains]. AB - A microspectrofluorimeter has been used for kinetic studies of the decrease of polycyclic aromatic hydrocarbons (PAH) fluorescence in single living cells (3T3 and RTG2 fibroblasts). These studies allow the determination of activation rate constants (k) for PAH. The distribution of the cellular populations has been represented as a function of k. The histograms show: an heterogeneity of the cellular population; differences between the metabolic activities of the two strains; modifications of the metabolization depending upon the probe tested. PMID- 3085886 TI - [Contribution to the anthropology of living Hungarians]. PMID- 3085887 TI - [Alpha-melanotropin in the frog brain: regional distribution, quantification and subcellular distribution]. AB - The distribution of alpha-MSH containing neurons was studied by immunofluorescence in the brain of the frog Rana ridibunda. Most immunoreactive cell bodies were found in the ventral hypothalamic area. A rich network of fluorescent fibers was observed in the ventral infundibular region, coursing towards the preoptic area and the ventral telencephalon. Some fibers, directed backwards, project into median eminence. By means of a specific radioimmunoassay, the concentrations of alpha-MSH immunoreactive material has been determined in 10 different regions of the brain. The highest concentrations were observed in the infundibular and the preoptic regions. Using the immunogold technique, electron microscopy showed that immunostaining was restricted to 70-100 nm dense core vesicles in positive cell bodies and fibers. These results suggest that, in addition to well known hormonal (melanotropic) activity, alpha-MSH could play the role of a neurotransmitter in the frog brain. PMID- 3085888 TI - Chest x-rays. PMID- 3085889 TI - Radiation sequelae. PMID- 3085890 TI - Serum vitamin D metabolites are not related to growth rate, bone mineral content, or serum alkaline phosphatase in male puberty. AB - Twenty boys were followed during their puberty for about 2 years with examinations every third month. At each examination we determined serum concentrations of 25OHD3, 1,25(OH)2D3, 24,25(OH)2D3, 25.26(OH)2D3, alkaline phosphatase (AP) and testosterone together with bone mineral content (BMC) at the distal forearm. Highly significant increases in both BMC (P less than 0.001), serum AP (P less than 0.001), and peak height velocity (PHV) followed the increase in serum testosterone. The boys were grouped according to time of maximal increase in BMC, AP, and PHV. The serum levels of the vitamin D metabolites were related to these points. No significant changes in any of the serum vitamin D metabolites were found. Thus vitamin D metabolism does not seem to be significantly influenced during the period of life when both the linear growth and bone mineralization is maximal. PMID- 3085891 TI - Effects of prostacyclin and prostaglandin E1 (PGE1) on bone resorption in the presence and absence of parathyroid hormone. AB - Prostaglandins have been shown to stimulate osteoclastic bone resorption in organ culture but morphologic studies of isolated osteoclasts have shown a transient calcitonin-like inhibiting effect of these agents. We looked for a dual effect on bone resorption by comparing the early and late effects of prostaglandin E1 (PGE1), prostacyclin (PGI2), 6 alpha-carbaprostaglandin I2 (C-PGI2), a carbon substituted analog of PGI2, and salmon calcitonin (CT) on the release of previously incorporated 45Ca from fetal rat long bones cultured in the presence of an inhibitor of cyclooxygenase, RO-20-5720. Experiments were performed in both the presence and absence of PTH (400 ng/ml), which was administered 24 hours before addition of prostaglandins or CT. In control cultures not stimulated by PTH, CT (100 mU/ml) produced significant decreases in 45Ca release at 48, 72, and 96 hours while PGE1 (10(-6) M), PGI2 (10(-5)), and C-PGI2 (10(-6) M) each produced significant increases in resorption at 24 through 96 hours. PGE1 at 10( 5) M, but not 10(-6) M, caused a significant decrease in medium 45Ca of 21% at 1 and 2 hours. Medium calcium measurements suggest that the change in 45Ca was due to inhibition of release and not to increased uptake. PGI2 (10(-5) M) and C-PGI2 (10(-6) M) caused no significant inhibitory effect. In cultures stimulated by PTH, CT produced significant inhibition of bone resorption of 6 through 96 hours, but no inhibition of bone resorption was noted at either early or late time points with PGE1, PGI2, or C-PGI2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085893 TI - Parathyroid hormone stimulates proliferation of chondroprogenitor cells in vitro. AB - Mandibular condylar explants of newborn ICR mice were maintained as serum-free organ culture systems and were used to study the effects of 0.1-10.0U/ml parathyroid hormone (PTH) on the morphology of the organ and the ultrastructure of the chondroprogenitor cells. Parameters of proliferation such as 3H-thymidine autoradiography and incorporation into the explants were also studied. The chondroprogenitoric zone gradually increased with increasing dosages of the hormone up to a maximum of 5-fold of the control with 5.0 U/ml PTH. Autoradiographic studies showed a 3-fold increase in the number of 3H-thymidine labeled cells in the chondroprogenitoric zone of PTH-treated explants. This was matched by a dose-dependent stimulation of 3H-thymidine incorporation, reaching maximal values at 5.0 U/ml PHT. At this concentration, the stimulated incorporation of 3H-thymidine was found to be dependent on the Ca2+ concentration of the medium. Chondroprogenitor cells located adjacent to the chondroblastic zone tended to pile up and aggregate in "syncytium"-like clusters, establishing intercellular gap junctions. All PTH-treated chondroprogenitor cells demonstrated large deposits of glycogen and highly elaborated stacks of their Golgi systems; the latter were associated with large numbers of vesicular elements. On the other hand, the chondroblastic zone was significantly reduced in size. Hence, it seems that PTH possesses a rather intense mitogenic effect upon chondroprogenitor cells and might possibly interfere with their normal pattern of differentiation into mature cartilage cells. PMID- 3085892 TI - Mineralized bone nodules formed in vitro from enzymatically released rat calvaria cell populations. AB - Single-cell suspensions obtained from sequential enzymatic digestions of fetal rat calvaria were grown in long-term culture in the presence of ascorbic acid, Na beta-glycerophosphate, and dexamethasone to determine the capacity of these populations to form mineralized bone. In cultures of osteoblastlike cells grown in the presence of ascorbic acid and beta-glycerophosphate or ascorbic acid alone, three-dimensional nodules (approximately 75 micron thick) covered by polygonal cells resembling osteoblasts could be detected 3 days after confluency. The nodules became macroscopic (up to 3 mm in diameter) after a further 3-4 days. Only in the presence of organic phosphate did they mineralize. Nodules did not develop without ascorbic acid in the medium. Dexamethasone caused a significant increase in the number of nodules. Histologically, nodules resembled woven bone and the cells covering the nodules stained strongly for alkaline phosphatase. Immunolabeling with specific antibodies demonstrated intense staining for type I collagen that was mineral-associated, a weaker staining for type III collagen and osteonectin, and undetectable staining for type II collagen. Nodules did not develop from population I and the number of nodules formed by populations II-V bore a linear relationship to the number of cells plated (r = .99). The results indicate that enzymatically released calvaria cells can form mineralized bone nodules in vitro in the presence of ascorbic acid and organic phosphate. PMID- 3085894 TI - Endocytosis precedes dissolution of basic calcium phosphate crystals by murine macrophages. AB - Murine peritoneal macrophages were incubated with 45Ca-labeled basic calcium phosphate (BCP) crystals in the presence or absence of cytochalasin B. Untreated macrophages solubilized 30-50% of 45Ca-BCP in 24 hours. Dissolution began within 3 hours and was linear thereafter. Twenty-three percent of BCP was cell associated by 3 hours. Endocytosis of crystal occurred continuously throughout the incubation. Endocytosis of crystal did not affect the migration of macrophages through Percoll density gradients. Addition of cytochalasin B did not prevent cell-association of BCP, but inhibited solubilization in a dose-dependent manner. Virtually all cell-associated BCP was removed when cytochalasin B-treated cells were washed with EDTA, suggesting that the crystals were only bound to the surface. In contrast, cell-associated BCP in untreated cells was only partially removed by EDTA, suggesting that endocytosis of crystal had occurred. We conclude that cell association of BCP is not sufficient for its dissolution, and that endocytosis precedes solubilization of BCP crystals by macrophages. PMID- 3085895 TI - Mixed-sclerosing-bone-dystrophy: 42-year follow-up of a case reported as osteopetrosis. AB - We present a detailed metabolic investigation and 42-year radiological follow-up of a 52-year-old man with mixed-sclerosing-bone-dystrophy, the rare occurrence of two or more distinct patterns of sclerosing-bone-dysplasia (e.g., osteopathia striata, osteopoikilosis, melorheostosis) in a single subject. Review of radiographs from 1942, when he was reported to have osteopetrosis, demonstrated diffuse osteosclerosis, osteopathia striata, osteopoikilosis, and focal cortical hyperostosis. Forty-two years later, there had been significant progression and evolution of his skeletal disease with the appearance of new areas of osteopathia striata and osteopoikilosis and a generalized increase in skeletal mass as assessed radiographically. Presence of subperiosteal bone apposition on biopsy of the iliac crest together with chronic mild hypocalcemia, secondary hyperparathyroidism, and hypophosphatemia suggested that enhanced bone formation, perhaps with defective skeletal resorption, is a fundamental abnormality which accounts for the increased bone mass of this patient. PMID- 3085896 TI - The role of skeletal calcium deficiency in postmenopausal osteoporosis. AB - A previous study of iliac crest composition identified skeletal calcium deficiency in 25% of 56 postmenopausal osteoporotic patients evaluated prior to the use of stanozolol or calcitonin. This report is a follow-up of biopsy data after 2 years of treatment with drug or placebo in 31 patients, 11 of whom had skeletal calcium deficiency. The study diet, consisting of 1 g elemental calcium plus 400 U Vitamin D, repaired the skeletal calcium deficiency in all patients, treated and untreated alike. Total body calcium (TBC) results were influenced by separation into calcium deficient and normal mineral groups, apparent treatment response being observed largely in patients with calcium deficiency. It is suggested that if all postmenopausal women ingested 1 g elemental calcium plus 400 U Vitamin D daily, skeletal calcium deficiency in osteoporosis would disappear as a problem. Meanwhile, it is important to recognize that repair of calcium deficiency is an important variable capable of influencing bone response to therapy and the evaluation thereof. PMID- 3085897 TI - Evidence that factors other than 1,25 dihydroxyvitamin D may play a role in augmenting intestinal calcium absorption in patients with primary hyperparathyroidism. AB - We examined 17 patients with primary hyperparathyroidism for their serum 1,25 dihydroxyvitamin D levels and for their fractional intestinal calcium absorption rates using a whole body counter and calcium-47. As controls, 10 normal volunteers were examined both before and after administration of 1 alpha hydroxyvitamin D to increase serum 1,25 dihydroxyvitamin D. Values of serum 1,25 dihydroxyvitamin D were 71.6 +/- 37.6 pg/ml (mean +/- SD) in patients with primary hyperparathyroidism and 75.3 +/- 27.7 pg/ml (mean +/- SD) in normal volunteers after administration of 1 alpha-hydroxyvitamin D, while values of intestinal calcium absorption rate were 61.5 +/- 16.5% (mean +/- SD) in patients with primary hyperparathyroidism and 34.1 +/- 5.1% (mean +/- SD) in normal controls, respectively. There was a positive correlation between values of serum 1,25 dihydroxyvitamin D and intestinal calcium absorption in both groups. However, in patients with primary hyperparathyroidism, intestinal calcium absorption was more increased than that in normal volunteers when compared to their serum values of 1,25 dihydroxyvitamin D. This suggests that another factor than 1,25 dihydroxyvitamin D plays an important role in the intestinal calcium absorption in patients with primary hyperparathyroidism. PMID- 3085899 TI - Short-term chronic fluoride administration and trabecular bone remodeling in beagles: a pilot study. AB - We carried out a pilot project to examine the alterations in trabecular bone remodeling activity of spayed Beagle dams exposed to 0.7 mg/kg body wt/day of sodium fluoride (NaF) for a 6 month period. The results indicated that short-term NaF administration does activate trabecular bone remodeling activity by stimulating the formation of new Basic Multicellular Units (BMUs) of bone remodeling activity. However, interference with bone cell differentiation, with the functional efficiency and/or life-span of individual osteoclasts and osteoblasts followed. Cellular toxic effects appear early with NaF administration, and as such, suggest that the increases in bone mass seen early in the course of NaF treatment may be negated by prolonged administration of this substance. However, preservation of bone mass will probably result with long-term therapy, due to decreases in numbers of bone cells, in their functional efficiencies, and in their individual life-spans. PMID- 3085898 TI - Modulation of bone loss during calcium insufficiency by controlled dynamic loading. AB - Changes in the midshaft cross-sectional area of the ulna were measured in egg laying turkeys on a diet insufficient in calcium. Left:right comparisons were used to assess the bone loss over a six-week period due to 1) calcium insufficiency, 2) calcium insufficiency plus disuse, and 3) calcium insufficiency and disuse interrupted by a short daily period of intermittent loading applied from an external device. Calcium insufficiency alone in the intact ulna resulted in a 15% reduction in cross-sectional area. In the functionally deprived bones this loss was increased to 32%. In bones where the disuse was interrupted by a single short daily period of loading, the degree of bone loss was significantly modified (P less than 0.006) to 25%. No significant difference in the modulating effect of loading was achieved by varying the peak strain from 0.0015 to 0.003, the strain rate from 0.01 to 0.05, or the duration of the single loading period from 100 sec per day to 25 minutes. All the loading regimes employed had been demonstrated to be osteogenic in mature male birds on a diet sufficient in calcium. PMID- 3085900 TI - Parathyroid glands, calcium, and vitamin D in experimental fluorosis in pigs. AB - The purpose of this study was to determine whether total serum calcium, parathyroid gland structure, and/or levels of parathyroid hormone, 1,25 and 24,25 DHCC, are altered in pigs with dental and skeletal fluorosis. Eight experimental animals receiving 2 mg F-/kg b.w. per day from age 8-14 months were compared with eight controls. Concentrations of plasma fluoride and total plasma calcium were assessed at intervals throughout the experiment and during a 48 hour period at day 110-111 of the experiment. At the same time, concentrations of immunoreactive parathyroid hormone were measured using a homologous labeled antibody for porcine hormone, and a radioimmunoassay was used to assess concentrations of 1,25 DHCC and 24,25 DHCC. Parathyroid tissue volumes were assessed at the end of the experiment by quantitative histology using volumetry and point counting. Plasma fluoride increased from 0.0007 +/- 0.0001 mmol/liter to 0.0127 +/- 0.002 mmol/liter in pigs receiving fluoride. In spite of this increase, total plasma calcium remained the same throughout the experiment. Volumes of parathyroid tissue, and levels of circulating parathyroid hormone 1,25 DHCC and 24,25 DHCC, were not significantly changed. It was therefore concluded that disturbance of calcium homeostasis is not an obligatory finding in dental and skeletal fluorosis and consequently does not play an essential role in the pathogenesis of these hard tissue lesions. PMID- 3085901 TI - Cytotoxic and migration inhibitory effects of bisphosphonates on macrophages. AB - Two in vitro model systems were developed to facilitate investigation of the mechanisms by which bisphosphonates block bone resorption. These systems assess the cytotoxic and the migration inhibitory activities of bisphosphonates using mouse peritoneal macrophages as osteoclast surrogates. Several bisphosphonates, 3 amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), dichloromethylene bisphosphonate (Cl2MBP), 1-hydroxyethylidene-1,1-bisphosphonate (HEBP), 1 hydroxybutylidene-1,1-bisphosphonate (HBBP), 1-hydroxyhexylidene-1,1 bisphosphonate (HHBP), and 1-hydroxyoctylidene-1,1-bisphosphonate (HOBP), possess the same relative activities in these systems as they do in bone resorption systems. Calcium ion replacement studies using these systems demonstrated that bisphosphonates do not derive all their activity from sequestration of calcium ions from cells by chelation. Whereas calcium ion replacement abrogated the activity of EDTA, a nonbisphosphonate calcium chelator active in both systems, it failed to abrogate either the cytotoxic or the migration inhibitory effects of the bisphosphonates tested. Calcium ion replacement increased the migration inhibitory activity of all the bisphosphonates tested. Further, calcium ion replacement increased the cytotoxicity of HHBP and HOBP; however, it decreased the cytotoxicity of HEBP, HBBP, AHPrBP, and Cl2MBP. PMID- 3085902 TI - Human parathyroid hormone (1-34) and salmon calcitonin do not reverse impaired mineralization produced by high doses of 1,25 dihydroxyvitamin D3. AB - We have reported recently that pharmacologic doses of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) stimulated bone matrix formation but impaired mineralization. The objective of this study was to determine if parathyroid hormone (hPTH 1-34) or calcitonin (sCT) would mineralize the osteoid induced by 1,25(OH)2D3 in rat long bones. In one experiment, male Sprague-Dawley rats were given daily subcutaneous injections of vehicle: 8 micrograms hPTH(1-34); 125 ng 1,25(OH)2D3; or both 8 micrograms hPTH and 125 ng 1,25(OH)2D3 per 100 g body weight for 12 days. In a second experiment, rats received daily injections of vehicle: 2 U sCT; 125 ng 1,25(OH)2D3; or both 2 U sCT and 125 ng 1,25(OH)2D3 per 100 g body weight for 18 days. Calcium (Ca), hydroxyproline (Hyp), and dry weight (DW) of the distal femur and serum calcium, phosphate, and serum bone Gla protein (BGP) were measured. In rats given both 1,25(OH)2D3 and hPTH, total bone DW and Hyp increased (P less than .01) without a corresponding increase in bone Ca so that Ca/Hyp decreased 47% (P less than .01) from control and remained comparable to values for rats treated with 1,25(OH)2D3 alone. In rats treated with both 1,25(OH)2D3 and sCT, total bone DW and Hyp increased while Ca decreased so that Ca/Hyp decreased 38% from control (P less than .05), and remained comparable to values for rats treated with 1,25(OH)2D3 alone. These results indicate that hPTH or sCT, given by intermittent injection to rats for 12 or 18 days respectively, failed to mineralize the osteoid induced by high doses of 1,25(OH)2D3. PMID- 3085903 TI - Surface activity on the periosteal and corticoendosteal envelopes following continuous progestogen supplementation in spayed beagles. AB - Resorptive and formative characteristics on the periosteal and corticoendosteal bone envelopes were assessed on the ribs of intact, spayed and medroxyprogesterone acetate (MPA)-supplemented Beagle dams. Histomorphometric analyses of the alterations on surface activities of these two envelopes were carried out using tetracycline labeling. It was found that continuous administration of progestogen decreased the extent of resorptive surfaces on the corticoendosteal surfaces of progestogen-treated animals vs. spayed animals. On the periosteal surfaces the progestogen-treated dogs showed a marked increase in formation when compared to spayed and intact dogs. As a result of continuous progestogen treatment, mineralization lag time was shortened on the corticoendosteum and periosteum of progestogen-treated animals when compared to the same surfaces on the bones of intact and spayed animals. PMID- 3085904 TI - Bone vitamin D-dependent calcium-binding protein is localized in chondrocytes of growth-plate cartilage. AB - The cellular distribution of vitamin D-dependent calcium-binding protein (CaBP) was examined in rat and chicken bone by immunocytochemical methods using an antiserum raised against purified chicken intestinal CaBP. In EDTA-decalcified, Vibratome sections of growing rat long bones, specific CaBP immunostaining was observed in cytoplasm of chondrocytes of the growth plate, particularly in regions of calcification. In undecalcified, frozen sections from neonatal rat, positive staining was seen in chondrocytes of tibial growth plate and also in chondrocytes of the long bones of the skull. No specific immunostaining was observed in osteoblasts, osteocytes or osteoclasts in mineralized bone. In frozen sections of tibias from 19-day-old chick embryos specific immunostaining was again confined to dividing chondrocytes of the growth plate and was much less intense in "resting" cartilage. The finding of CaBP in chondrocytes, cells known to possess specific receptors for 1,25-dihydroxyvitamin D3 and to respond to the hormone, suggests a possible functional role for CaBP in chondrocyte maturation, differentiation and/or cartilage calcification. PMID- 3085905 TI - Interaction between oxygen and the blood vessel wall. AB - Blood vessels in vivo respond to changes in the supply of oxygen relative to its demand. Whether the vessels which participate in such vasoregulatory responses are directly affected by oxygen remains an open question. Most studies of oxygen sensing by blood vessels have been carried out on strips, rings or segments isolated from relatively large vessels. These preparations are generally sensitive to oxygen from 0 mm Hg to some upper PO2 (10 to 240 mm Hg) whose value depends on experimental conditions. It appears unlikely that reduced energy production secondary to tissue hypoxia is directly responsible for the relaxation usually observed when PO2 is lowered below a critical value. Evidence that an oxygen-linked chemical mediator such as adenosine or prostacyclin is involved in contractile responses to lowered PO2 has been obtained. The site of action of oxygen could be anywhere within the vascular wall, but current evidence suggests a prominent role for the endothelial cells. At present extrapolation of these results to resistance vessels in vivo must be carried out with caution due to potential differences in the behaviour of microvessels relative to large vessels. PMID- 3085907 TI - Retinitis pigmentosa: immunohistochemical and biochemical studies of the retina. AB - Several immunohistochemical and biochemical characteristics of retinas from two patients with retinitis pigmentosa (RP) were examined. Histochemically, interphotoreceptor retinoid-binding protein (IRBP) was found in the interphotoreceptor space in small areas of preserved peripheral retina, although enzyme-linked immunosorbent assay suggested that little IRBP was present. Antibodies to glial fibrillary acidic protein and factor VIII-related antigen corroborated retinal gliosis and retinal vessel attenuation, respectively, in the RP cases. Fibronectin showed similar staining in normal and affected tissue. PMID- 3085906 TI - The acute hemodynamic response to pirbuterol at rest and exercise in patients with heart failure with observations on long-term response. AB - Rest and exercise hemodynamics with the beta agonist pirbuterol and a placebo preparation were studied in seven patients with severe chronic congestive heart failure. At rest, pirbuterol increased cardiac index (1.8 +/- 0.3 to 2.3 +/- 0.4 L/min/M2, p less than 0.01) and decreased systemic vascular resistance (1899 +/- 405 to 1419 +/- 257 dynes-sec-cm-5, p less than 0.01) without a significant change in heart rate, right atrial, pulmonary arterial, pulmonary arterial wedge, or systemic arterial pressures. Although there were slight increases in cardiac index at peak exercise with pirbuterol, neither total exercise time nor peak oxygen consumption were improved with this agent. No significant hemodynamic changes occurred with placebo at rest, nor was there improvement in exercise performance following placebo. Of three patients studied at six weeks, two showed total loss of hemodynamic effect of pirbuterol compared to the acute response. In conclusion, although acute rest hemodynamics improve with pirbuterol, the lack of improved acute exercise performance and the decrease in hemodynamic responsivity at six weeks appear to limit its usefulness in the treatment of heart failure. PMID- 3085908 TI - Studies on a modulatory role for adenosine in antigen and arachidonic acid induced contractions of guinea pig airways. AB - The modulatory effects of adenosine and selected derivatives were examined on antigen and arachidonic acid (AA) induced contractions of indomethacin-treated tracheal spirals and lung parenchymal strips from actively sensitized guinea pigs. Adenosine (up to 2 X 10(-4) M) had no effect on antigen-induced contractions, but inhibited AA-induced contractions by 30-40% if added 30 min prior to challenge. The weak effect of adenosine suggests that endogenous adenosine may only have a limited modulatory role in allergic bronchospasm. 2 Chloroadenosine (10(-6)-10(-4) M) dose-dependently inhibited antigen- and AA induced contractions of trachea, but was considerably less effective on parenchyma. The substituted adenosine derivatives, R-phenylisopropyladenosine (R PIA) and 5'-(N-ethylcarboxamido)-adenosine (NECA), and the adenosine transport inhibitor, 6-[p-nitrobenzyl)thio]-9-beta-D-ribofuranosyl purine, were also active as modulators, but their activity was relatively weak and varied with the stimulus and the tissue. An order of potency for R-PIA, NECA, and 2 chloroadenosine could not be determined and 8-phenyltheophylline (10(-5) M) was not an effective inhibitor of the effects of adenosine or the adenosine derivatives. This suggests that adenosine and its derivatives may modulate cells through mechanisms other than activation of conventional A1 and A2 receptors. A lack of specificity for the adenosine derivatives must also be considered. PMID- 3085909 TI - Comparative effects of the ionophore A23187 on the mechanical responses of muscle in normal Pietrain pigs and pigs with malignant hyperthermia. AB - Since increased intracellular Ca2+ is believed to be the main factor causing skeletal muscle contracture in human and porcine malignant hyperthermia, the potential effects of the ionophore A23187, which enhances intracytoplasmic Ca2+, were investigated in Pietrain pig muscles. These effects were compared with those of caffeine, known to induce dose-dependent contracture in vitro in isolated muscle from human subjects with malignant hyperthermia. For this purpose, the mechanical and biochemical actions of caffeine and A23187 were tested in intercostal muscle biopsies from 10 normal pigs and 10 with malignant hyperthermia. The results show that A23187 allowed very clear differentiation between the muscles of normal and pathological animals. In view of the wide spectrum of drug sensitivity characterizing subjects with malignant hyperthermia, it is suggested that exposure to A23187 be added to the halothane and caffeine tests currently used to detect this disease. PMID- 3085910 TI - Lipopolysaccharide changes and cytoplasmic polyphosphate granule accumulation in Pseudomonas aeruginosa during growth on hexadecane. AB - Pseudomonas aeruginosa ATCC 9027 grew on 0.5% (v/v) hexadecane as a sole carbon source in a chemically defined medium which required the addition of Fe3+ and Ca2+. There was a variable and extended lag period before an active growth rate was attained. Visible light microscopic evidence revealed that the bacteria did not adhere to hexadecane droplets suggesting the absence of a bioemulsifier. When compared with glucose-grown cells, hexadecane-grown cells produced 75% less lipopolysaccharide (on a total protein basis); this lipopolysaccharide contained 30-40% less carbohydrate, yet 50-75% more 2-keto-3-deoxyoctonate. These chemical changes made the cell surface appear more hydrophobic when tested in a biphasic hydrophobicity index system. Electron microscopy of thin sections and freeze etchings revealed hexadecane-grown cells contained granules which were judged to be polyphosphate by energy dispersive X-ray analysis. There was no apparent major morphological envelope alteration within the two cell types. PMID- 3085911 TI - Pregnancy in the hyperprolactinaemic patient. AB - Once other causes of hyperprolactinaemia have been excluded it is reasonable to assume that the cause lies within the hypothalamus or the pituitary. The pituitary may be the site of lactotroph hypertrophy and hyperplasia, a micro adenoma or a macro-adenoma. Sixty-nine pregnancies in 53 patients, who required treatment of hyperprolactinaemia prior to the onset of pregnancy, have been observed. It is the purpose of this review to describe these patients, discuss the effects of pregnancy upon any pituitary lesion, and to discuss the effects of hyperprolactinaemia or the treatment of hyperprolactinaemia upon pregnancy. Based upon experience and the discussion of these data, recommendations for treatment of the hyperprolactinaemic pregnant patient will be made. PMID- 3085912 TI - [Rapid response of a disorder to the addition of lithium carbonate: panic resistant to tricyclic antidepressants]. AB - There is evidence that panic disorder and major depression might share some common neurobiological factors. This would be consistent with the fact that most antidepressant drugs are effective in preventing panic attacks. This is a case report of a 40 year old woman who was suffering from a panic disorder. Following the discontinuation of a long-term lorazepam treatment, she developed severe depressive symptoms. The depressive syndrome improved rapidly with amitriptyline (150 mg/day), but the panic attacks persisted. Twelve weeks later, amitriptyline was replaced by clomipramine (150 mg/day), the dosage of which was increased to 225 mg/day three weeks later. The patient remained anxious with no resolution of her panic attacks. Two weeks later, lithium carbonate (900 mg/day) was added to clomipramine. Sixty hours later, a dramatic improvement was observed. The lithium plasma level was 0.8 mEq/L. Because of some tremors, lithium was discontinued five days later. Within four days, the anxiety as well as the panic attacks reappeared. Lithium carbonate (600 mg/day) was then resumed. Forty-eight hours later, the patient was showing a clinical improvement similar to that observed following the first addition of lithium. She remained symptom free with the maintenance of the drug combination. To date, several reports have confirmed the beneficial effect of adding lithium to a tricyclic antidepressant drug in resistant major depression. However, we believe that the present case report is the first one documenting the augmentation of a tricyclic antidepressant drug by lithium in a patient suffering from a panic disorder. PMID- 3085913 TI - Plasmacytoma of the thyroid gland. AB - Primary plasmacytoma of the thyroid gland is a rare disease, and clinicopathologic features of this disease are not fully understood. Six cases of primary plasmacytoma of the thyroid, in which immunoperoxidase procedures confirmed a monoclonal nature of proliferating plasma cells are presented. All patients had antithyroid antibodies in their serum together with histologic evidence of chronic lymphocytic thyroiditis, suggesting an intimate relationship of these diseases. Review of the literature revealed that 18 cases, 14 cases from Western countries and 4 cases from Japan, described primary thyroid plasmacytoma. The authors summarized the clinicopathologic features in the current and previously reported cases. PMID- 3085915 TI - Enhanced radiotolerance to ionizing radiation is correlated with increased cancer proneness of cultured fibroblasts from precursor states in neurofibromatosis patients. AB - We have determined the sensitivity to gamma rays of cultured fibroblasts derived from clinically defined areas on the skin of neurofibromatosis patients. Fibroblasts from skin of normal appearance were normally sensitive to gamma irradiation. Significantly, however, fibroblasts from cafe-au-lait lesions and from neurofibromas were abnormally radiotolerant (about twofold) to treatment with gamma rays. This was seen in specimens taken from the same patient, as well as from different patients, within four different neurofibromatosis pedigrees. In contrast, no differences in radiosensitivity have been observed between fibroblasts derived from skin of normal appearance and those obtained from melanotic freckles of individuals with no family history of cancer. The results suggest that increased propensity to cancer in this cell system is associated with increased radiotolerance to ionizing radiation. PMID- 3085914 TI - Improved protein kinetics and albumin synthesis by branched chain amino acid enriched total parenteral nutrition in cancer cachexia. A prospective randomized crossover trial. AB - A prospective randomized crossover trial was conducted to determine the effect of a branched chain amino acid (BCAA)-enriched solution on whole body leucine kinetics and fractional rates of albumin synthesis in patients with intra abdominal metastatic adenocarcinoma. Ten malnourished cancer patients were provided isonitrogenous amounts of both a conventional total parenteral nutrition (TPN) formula containing 19% BCAA and a BCAA-enriched TPN formula containing 50% of the amino acids as BCAA in a random order. Whole body protein turnover was determined by a 10 hour continuous infusion of leucine 14C. Increased whole body leucine flux (68 +/- 5 mumols/kg BW/hr versus 145 +/- 11; mean +/- SEM; P less than 0.001) and oxidation (13 +/- 2 mumols/kg BW/hr to 46 +/- 5; P less than 0.001) were determined on the BCAA-enriched TPN. Increased whole body protein synthesis (2.2 +/- 0.2 g protein/kg BW/day versus 3.9 +/- 0.3; P less than 0.005) and leucine balance (2.5 +/- 0.4 g leucine/d versus 6.5 +/- 0.6; P less than 0.001) were also observed in patients receiving the BCAA-enriched TPN solution. Leucine release from protein breakdown was not statistically elevated (1.65 +/- 0.18 g protein/kg BW/d versus 2.48 +/- 0.40; P greater than 0.05) but, incorporation of leucine 14C into plasma albumin was significantly elevated (2.37 +/- 0.23 mumols/g/hr to 4.21 +/- 0.33; P less than 0.001) when the patients received BCAA-enriched TPN. Despite the better leucine balance, the improvement in the 24-hour urinary nitrogen balance was not statistically significant (6.6 +/ 3.9 g protein/d versus 11.4 +/- 2.9; control versus BCAA-enriched; P = 0.15). BCAA-enriched formulas improve whole body leucine kinetics, fractional rates of albumin synthesis, and leucine balance, and thus may favorably influence protein metabolism in cancer cachexia. PMID- 3085916 TI - Cytogenetic studies in four cases of alpha chain disease. AB - Cytogenetic studies were performed in four cases of alpha chain disease. Chromosomal abnormalities were found in the lymphoid cells of the mesenteric lymph nodes of three patients, two of whom had not reached the stage of overt malignant lymphoma. In two instances, a rearrangement of 14q32, resulting from a t(9;14)(p11;q32) and a t(2;14)(p12;q32) was observed. One case showed complex rearrangements including t(5;9). No abnormalities were found in the intestinal tumor of the fourth case with immunoblastic lymphoma. It is concluded that alpha chain disease is a clonal proliferation with frequent alteration of chromosome #14 at band q32 resulting from translocations that differ from those observed in the vast majority of other non-Hodgkin lymphomas. PMID- 3085917 TI - Early detection--the priority in colorectal cancer. PMID- 3085918 TI - Measurement of aflatoxin B1, its metabolites, and DNA adducts by synchronous fluorescence spectrophotometry. AB - Sensitive and specific methods are needed for measuring human exposure to carcinogens. Synchronous fluorescence spectrophotometry can be used to measure fmol of aflatoxins, their metabolites, and DNA adducts. Computer-assisted analysis of spectra of these agents obtained by synchronous fluorescence spectrophotometry can be displayed as contour maps which are highly specific for each agent. Individual agents in mixtures, e.g. aflatoxins B1 and M1, can be identified by fourth derivative spectral analysis. This physical method should complement immunological and other methods to measure aflatoxin B1, its metabolites, and nucleic acid adducts. PMID- 3085919 TI - Vascular reactivity to norepinephrine of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors and normal tissue as studied in vitro. AB - Vascular reactivity to norepinephrine has been studied in dimethyl benz(a)anthracene-induced rat mammary neoplasia and compared with that of skeletal muscle, salivary gland, kidney, and uterus by means of an artificial perfusion technique. Perfusion of tissues and organs was measured with the microsphere tracer technique during smooth muscle relaxation and infusion of norepinephrine at two different dose levels. This procedure makes possible a dose response analysis of several tissues under controlled conditions without confounding endogenous vasoregulation. The tumor vascular bed has a low perfusion capacity during smooth muscle relaxation and responds rapidly with an increased resistance to norepinephrine infusion. The results indicate a hypersensitivity, although the relative maximal constrictor response is equal to or less than that of other vascular beds studied. PMID- 3085920 TI - Binding of human gamma-interferon to human epidermal tumor cells with different susceptibilities. AB - The in vitro antiproliferative effect of highly purified recombinant human gamma interferon was studied with special reference to specific binding to tumor cells of interferon (IFN) labeled with 125I. Recombinant human gamma-interferon markedly suppressed the growth of 6 of 10 human epidermal tumor cell lines tested; the concentration required to inhibit the growth of susceptible cell lines by 50% ranged from 8 to 36 units/ml (13.6 to 61.2 pM), whereas those for the other cell lines were higher than 10,000 units/ml. These anticellular effects were compatible with the suppressive effects of IFN on cellular DNA synthesis. Labeled IFN bound specifically to the susceptible cells, which showed, from the Scatchard analysis, 870 to 7700 binding sites/cell with apparent Kd of 1.70 to 5.84 X 10(-11) M. There was little binding of the labeled IFN to the resistant cells and nonspecific binding occurring in the presence of a 1000-fold excess of unlabeled IFN accounted for 40 to 90% of the total binding. These results suggest that specific binding sites for recombinant human gamma-interferon exist on the resistant cell lines. PMID- 3085921 TI - Regulation of the proliferation of the established human monoblast cell line, U937, at the single cell level. AB - U937 cells, an established monoblast or early monocyte cell line, were assessed as a model in vitro for the regulation of cell growth at the single cell level. Colony formation by 500 U937 cells, preinduced to a state of responsiveness to lactoferrin (LF) by incubation with human gamma interferon was suppressed by LF. LF-suppressed colony formation was restored by partially purified growth activity derived from U937 cells. The release of growth factor(s) into conditioned medium required concentrations of greater than 500 U937 cells/ml and this release was dependent on the length of time that the cells conditioned the culture medium. This release was suppressed by LF. U937 cells were induced to a state of responsiveness to LF by incubation with human gamma interferon, washed, and plated as a single cell per well. Individual cells formed colonies with a cloning efficiency of approximately 50% which equalled the cloning efficiency detected when 500 U937 cells/ml were plated, suggesting that U937 colony forming cells might contain endogenous growth activity. Detection of these endogenous growth activities required the use of LF. The cloning efficiency of individually isolated U937 cells was suppressed by approximately 50% with LF, similar to the LF suppression of colony formation when 500 cells/ml were plated. That the LF suppressed U937 colony forming cells required growth activity was suggested as the cloning efficiency of LF-suppressed individually isolated U937 colony forming cells was restored by partially purified U937 growth activity. Partially purified U937 growth activity did not stimulate, enhance, or inhibit colony formation by normal human bone marrow granulocyte-macrophage progenitors. U937 cells can thus serve as a useful model for the study of growth regulation at the level of a single cell. PMID- 3085922 TI - Additive and differential biological activity of alpha-interferon A, difluoromethylornithine, and their combination on established human lung cancer cell lines. AB - The effect of human recombinant leukocyte interferon A (IFN-alpha A) and DL-alpha difluoromethylornithine (DFMO) as single drugs and in combination on the in vitro growth, cell cycle distribution, activity of the enzyme L-dopa decarboxylase, and expression of the c-myc and N-myc oncogenes was studied in human lung cancer cell lines. In vitro growth activities were tested in concentrations ranging from 10 to 50,000 IU/ml for IFN-alpha A and from 0.1 to 10 mM for DFMO by means of the soft agarose clonogenic assay using continuous drug exposure. Ten well established small cell lung cancer (SCLC) cell lines including five cell lines of the classic and five of the variant phenotype, two cell lines derived from adenocarcinoma of the lung, and one large cell lung cancer cell line were included in the study. We found that IFN-alpha A inhibited the growth only of the variant phenotype of SCLC with an approximate drug concentration yielding a 50% inhibition of colony growth of 1000 IU/ml. None of the SCLC classic cell lines was inhibited significantly. The growth inhibition of IFN-alpha A correlated with the proliferation rate of the tumor. IFN-alpha A inhibited one of two adenocarcinoma cell lines and 0 of 1 large cell lung cancer cell line. DFMO inhibited the colony formation of 10 of 10 SCLC cell lines, 2 of 2 adenocarcinoma cell lines, and 0 of 1 large cell lung cancer cell line with a drug concentration yielding a 50% inhibition of colony growth of 1 mM. No difference between the classic and variant phenotypes of SCLC was found. The combination of IFN-alpha A and DFMO resulted in an additive cytostatic effect in all cell lines tested. The same result, i.e., an additive cytostatic effect, was obtained for two SCLC cell lines that were tested in liquid culture. Neither single drugs nor their combination led to an accumulation of cells in a particular phase of the cell cycle nor did it affect the activity of the SCLC classic marker enzyme L-dopa decarboxylase. In addition, IFN-alpha A, DFMO, and their combination did not affect the expression of the c-myc and N-myc oncogenes in cell lines NCI-N417 and NCI-H526, respectively, following 4, 24, and 72 h of continuous drug exposure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3085923 TI - Effect of moderate vitamin A supplementation and lack of dietary vitamin A on the development of mammary tumors in female rats treated with low carcinogenic dose levels of 7,12-dimethylbenz(a)anthracene. AB - We examined the effect of moderately increased and of marginal continued dietary supplementation of vitamin A (retinyl acetate) and the effect of lack of dietary vitamin A on the initiation and promotion stages of mammary tumorigenesis in female Sprague-Dawley rats treated with a single low (0.5 mg/100 g body weight) or very low (0.1 mg/100 g body weight) dose of i.v.-administered 7,12 dimethylbenz(a)anthracene. The number of mammary tumors was significantly (P less than 0.05) reduced if prior to and during initiation with 7,12 dimethylbenz(a)anthracene the rats were fed a moderately increased (30 micrograms/day) or marginal (3 micrograms/day) amount of vitamin A, compared to rats fed an adequate (10 micrograms/day) amount of vitamin A. The number of mammary tumors was also significantly (P less than 0.05) reduced when a moderately increased or marginal amount of vitamin A was provided during the tumor promotion phase. In addition, the number of mammary tumors was significantly (P less than 0.05) reduced by the lack of dietary vitamin A during both the initiation and promotion stages of this tumorigenic process, when compared to vitamin A adequate, ad libitum-fed rats, but not when compared to vitamin A adequate, food-restricted controls. The reduction in numbers of mammary tumors observed in these studies was reflected primarily in significant (P less than 0.05) decreases in mammary fibroadenomas; the number of mammary carcinomas was often reduced, but due to a low frequency of the carcinomatous lesions, this reduction did not reach the 5% level of statistical probability. Plasma and liver vitamin A levels were determined during both the initiation and promotion stages. As the dietary supplementation of vitamin A increased from 0 to 30 micrograms/day, there was an increase in mean liver and plasma vitamin A levels. No consistent correlation between plasma and liver vitamin A levels and the occurrence of mammary tumors was observed, except with the moderately increased (30 micrograms/day) intake of vitamin A, that resulted in a small, but statistically significant (P less than 0.05) increase of serum retinol at initiation; this may account for the observed reduction in mammary tumors. These results provide evidence that moderate alterations in vitamin A consumption can modulate low-dose chemically induced mammary gland tumorigenesis. Most importantly, suppression of mammary gland tumorigenesis can be achieved by moderately increased, frequent, and regular consumption of vitamin A; prolonged consumption of vitamin A-deficient diets or diets marginal in vitamin A does not enhance the risk of mammary tumor development. PMID- 3085924 TI - Effect of alpha-difluoromethylornithine alone and in combination with doxorubicin hydrochloride, cis-diamminedichloroplatinum (II), and vinblastine sulfate on the growth of P3J cells in vitro. AB - alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, was examined as a single and combined agent in growth studies using P3J, a Burkitt's lymphoma cell line. Used alone, DFMO (greater than or equal to 50 micrograms/ml; 0.21 mM) prevents cell proliferation in liquid culture and reduces the number and size of colonies that form in a two-layer soft agar system. In combination studies in which the soft agar system was used, DFMO was used at 15 and 25 micrograms/ml, concentrations which reduced the number of colonies to approximately 65 and 50%, respectively, of control plates. When doxorubicin hydrochloride (Adriamycin) was combined with DFMO, synergistic effects were noted at both DFMO concentrations. Cisplatin and DFMO were synergistic at the higher DFMO concentration and were supraadditive at 15 micrograms DFMO/ml. Combination studies using vinblastine sulfate (Velban) with DFMO did not deviate significantly from the predicted additive response. PMID- 3085925 TI - Protective effect of sodium-2-mercaptoethanesulfonate on the gastrointestinal toxicity and lethality of cis-diamminedichloroplatinum. AB - cis-Diamminedichloroplatinum (cis-platinum) is an effective and widely used antitumor drug. Patients receiving cis-platinum, however, experience very profound and long lasting gastrointestinal symptoms. The role of intestinal mucosal toxicity in the pathogenesis of these symptoms is unclear. In this study we have investigated the thiol-containing compound mesna (sodium-2 mercaptoethanesulfonate) as a potential antidote to cis-platinum-induced gastrointestinal tract damage. In mice, mesna caused a significant reduction in the gastrointestinal toxicity of cis-platinum assessed by electron microscopy, villus recovery rate, and by disaccharidase estimations. Mesna also significantly reduced serum creatinine levels following cis-platinum. Administration of mesna prior (or immediately following) a 67% lethal dose of cis-platinum protected 87 100% of the animals from the lethal effects. The antitumor efficacy of cis platinum in L1210 leukemia bearing mice was not affected by coadministration of mesna indicating that the protective effect may be tissue specific. In addition this finding indicates that mesna has potential as an agent which may improve the therapeutic index of cis-platinum in clinical practice. PMID- 3085926 TI - Protection of mitochondrial genetic system against aflatoxin B1 binding in animals resistant to aflatoxicosis. AB - Administration of a single dose of aflatoxin B1 (AFB1) (6 mg/kg) to Sprague Dawley rats results in a high level of modification of hepatic mitochondrial DNA (2.1 nmol of AFB1 adducts per mumol DNA-phosphate) and long-term inhibition of mitochondrial transcription and translation activities (N. Bhat et al., Cancer Res., 42: 1876-1880, 1982). Similar doses of AFB1 given to ICR mice and Syrian golden hamsters result in negligible to very low levels (0-06 nmol) of adducts in hepatic mitochondrial DNA. Intact mitochondria from rat liver can metabolize significant amounts of AFB1 (0.29 nmol/mg of protein) without externally added reduced nicotinamide adenine dinucleotide phosphate, and the metabolic activity is stimulated nearly 3-fold by Kreb's cycle intermediates (glutamate and malate), which support intramitochondrial reduced nicotinamide adenine dinucleotide phosphate production. Intact mitochondria from mice and hamsters, on the other hand, metabolize negligible or very low levels of AFB1 (0-0.1 nmol of AFB1 per mg of protein) even when intramitochondrial reduced nicotinamide adenine dinucleotide phosphate production is stimulated by the addition of Kreb's acids. Detergent-solubilized mitoplasts containing less than 1% microsome contamination from all three sources can catalyze the metabolic activation of AFB1 to electrophilic reactive forms as determined in an in vitro DNA binding assay at comparable levels (1.2-2.2 nmol of AFB1 bound per mumol of cytochrome P-450), suggesting that the low levels of AFB1 metabolism by intact mouse and hamster mitochondria and the relative resistance of macromolecular synthesis in these particles to added AFB1 may be due to mitochondrial membrane impermeability. In support of this possibility, AFB1 transported into mouse liver mitochondria through a liposome delivery system causes about 80% inhibition of protein synthesis. PMID- 3085927 TI - Effect of supplemental carbidopa on bioavailability of L-dopa. AB - The effect of doubling carbidopa intake on single dose bioavailability of L-Dopa was examined in five parkinsonian patients. Increasing carbidopa from a mean of 145 to 290 mg/day caused a mean increase in peak plasma Dopa concentrations from 1,893 +/- 476 to 2,733 +/- 607 ng/ml and area under the Dopa plasma concentration versus time curve of 24.6 +/- 10.0%, as well as a decrease in the time to peak plasma concentration to 0.7 +/- 0.2 versus 1.2 +/- 0.3 h. Increasing the within dose ratio of carbidopa to L-Dopa, even in patients receiving "maximally effective" doses of carbidopa, further increases bioavailability of L-Dopa, presumably by inhibiting "first pass' metabolism in the gut. PMID- 3085928 TI - Delayed onset of responses to single doses of L-dopa in parkinsonian fluctuators on long-term L-dopa therapy. AB - Dose-related fluctuations in response to L-Dopa such as the "wearing-off" phenomenon are a common side effect of long-term L-Dopa therapy. In a retrospective clinical analysis, 18 of 32 chronically treated parkinsonian fluctuators developed a delay in onset of a beneficial effect induced by single doses of L-Dopa. In these patients, there was a threefold increase in latency from ingestion of the first morning dose to "start-up" of a response (from 0.4 +/ 0.2 to 1.1 +/- 0.3 h) in parallel to a twofold decrease in its duration (from 4.2 +/- 1.1 to 1.7 +/- 0.8 h). Longer durations of illness and of L-Dopa therapy, occurrence of totally ineffective doses, poorer responsiveness to afternoon and evening doses, and early-morning dystonia were more prevalent in this group. In 14 of the 32 parkinsonian fluctuators, monitored "start up" of clinical effect occurred at about an hour after the first morning oral dose of L-Dopa. The dose induced elevations in plasma L-Dopa levels started after a mean of about 0.5 h and were maximal at 1.25 h. The study suggests that prolongation of "start-up" latencies in response to single doses of L-Dopa is a rather common complication of chronic treatment and may increase patients' disability by further decreasing the duration of daily "on" periods. Causes for this phenomenon are unknown but retarded absorption of orally administered L-Dopa may be important. PMID- 3085929 TI - New perspectives in the treatment of Parkinson's disease. PMID- 3085930 TI - Phase I trial of recombinant interferon gamma by 1-hour i.v. infusion. AB - Fifteen patients with advanced malignancy were treated with recombinant interferon gamma (rIFN-gamma) (specific activity approximately 2 X 10(7) units/mg, purity greater than 99%) given by 1-hour iv infusion three times a week for 6 weeks, at fixed dose levels of 0.1, 0.5, 1.0, or 2.0 mg/m2/day. The common side effects were constitutional symptoms, including fever, chills, myalgias, and headache, but these were less severe than those observed following daily 6-hour iv infusions. Significant changes in blood cell counts and routine serum chemistries were not observed, but there was a dose-dependent increase in serum triglyceride levels. The maximum safely tolerated dose achieved was 1.0 mg/m2/day. Peak serum interferon levels occurred at the midpoint of the infusion and were dose-dependent. rIFN-gamma was rapidly cleared from serum and no detectable activity was found 2 hours after the infusion. Two patients, both with B-cell malignancies, showed objective evidence of tumor regression during the treatment. Treatment was associated with an increase in serum levels of beta 2 microglobulin and the H2O2 secretory capacity of peripheral blood monocytes. We conclude that rIFN-gamma administered by short iv infusion can induce biological activities and causes less toxicity than when given by prolonged iv infusion. PMID- 3085931 TI - Direct measurement of the rate of ring opening of D-glucose by enzyme-catalyzed reduction. PMID- 3085932 TI - Cardiac arrhythmias in the elderly: antiarrhythmic drug treatment. AB - The frequency of ventricular arrhythmias increases with age. Several factors make elderly people more prone to antiarrhythmic drug toxicity. Familiarity with the changes in the pharmacokinetics and pharmacodynamics of antiarrhythmic agents may reduce or prevent adverse response in this patient population. PMID- 3085934 TI - Utility of foot venography as part of the routine lower-extremity venogram: a prospective study. AB - Two-hundred foot venograms were performed in patients suspected of deep vein thrombosis (DVT). Eighty studies were positive for DVT in the calf, popliteal, superficial femoral, or common femoral veins. Of these, 16 (20%) had an associated venous thrombosis in the foot. One hundred and ten studies were negative. Of these, none had a positive foot venogram. It is therefore our feeling that an additional study of the foot need not be performed unless there are symptoms specifically referable to this area. PMID- 3085933 TI - Pacemaker implantation in a patient with a Behcet's disease associated with superior vena cava obstruction. AB - A 65-year-old man with Behcet's disease developed transient complete A-V block with syncope. An attempt to implant a permanent transvenous endocardial electrode failed owing to obstructions in the subclavian, innominate, and superior vena cava veins demonstrated by angiography. Sutureless epicardial electrodes were successfully implanted through a subxyphoid approach. Obstruction in the great veins is a common feature in patients with Behcet's disease. We suggest that patients with this disorder, who require a permanent pacemaker, should be investigated by angiography prior to implant to rule out obstruction in the upper great veins. PMID- 3085935 TI - Traumatic aortocaval fistula presenting as atypical chest pain. PMID- 3085936 TI - Calcified thrombus of the inferior vena cava in transposition of the great vessels. AB - Calcified thrombus of the inferior vena cava (IVC) in children is an entity usually not associated with significant complications. The possibility of pulmonary embolism from the soft thrombus, however, has been suggested but never reported. We give an account of a child with transposition of the great vessels who suffered embolization from a calcified thrombus in the IVC that entered the systemic circulation. PMID- 3085937 TI - Simplified technique of internal pudendal angiography in the investigation of impotence. AB - The authors describe a simplified method for evaluating the arterial status of the penis in patients with impotence. Internal pudendal angiography employing the "flour-bag" technique will likely become a routine procedure for angiographers. PMID- 3085938 TI - Massive hemorrhage into a periappendiceal abscess: case report. AB - A case of significant hemorrhage into an ileal wall periappendiceal abscess in a 62-year-old man is described. Pathologic correlation of an unusual collection of contrast seen at the distal end of a branch of the ileocolic artery during angiography is discussed and illustrated. PMID- 3085939 TI - Duodenal fistula--a rare complication following the removal of an infected aortic graft: case report. AB - We present a rare case of fistulation from the duodenum into the prosthesis site of an aortic Y graft removed 8 months previously owing to infection. We have verified the topographical and anatomical location of the fistulation by fistula filling and CT and MR examination. To our knowledge such a postoperative complication has not been previously documented. In evaluating and comparing our observation we discuss their significance for topographical associations and prognosis and as an indication for surgical intervention. PMID- 3085940 TI - Aortic dissection masquerading as gastrointestinal disease. AB - Presentation of aortic dissection (AD) typically includes chest and/or abdominal pain. Gastrointestinal (GI) symptoms other than abdominal pain are uncommon. Two patients with AD are described in whom the dominant presenting symptom was GI hemorrhage. Mesenteric infarction complicated acute Type I dissection in one patient whose clinical manifestations simulated ulcerative colitis. In the other patient an old, small asymptomatic Type III AD resulted in a false aneurysm in the retroperitoneum which ruptured into the duodenum. In the latter case an antemortem diagnosis was not made as angiography was limited to the visceral arteries and the abdominal aorta without appreciation of the significance of a focal compression of the abdominal aorta. The possibility of AD thus should also be considered in the evaluation of a patient with acute GI bleeding. PMID- 3085941 TI - Use of giant steel coils in the therapeutic embolization of a superior mesenteric artery-portal vein fistula. AB - The use of a series of giant steel coils is described for the therapeutic embolization of a post-traumatic arteriovenous fistula between the superior mesenteric artery and the portal vein. PMID- 3085943 TI - A new catheter for selective and superselective angiography. AB - A new femorovisceral catheter has been developed that facilitates routine selective abdominal angiography as well as superselective catheterizations out to fourth-order visceral branches. This design has proved to be particularly effective for embolization and infusion procedures. PMID- 3085942 TI - Hepatopetal collaterals after portal vein thrombosis following liver transplantation. AB - Two liver transplant patients with hepatopetal collaterals after portal vein thrombosis are described. Angiographically, the appearance is similar to cavernous transformation of the portal vein. The demonstration of hepatopetal collaterals is diagnostic of portal vein occlusion from whatever cause. After portal vein occlusion, collaterals develop from preexisting periportal vessels which undergo compensatory enlargement and reconstitute the intrahepatic portal vessels. In liver transplant patients, the collateral communications must arise de novo, since all potential collateral pathways are severed at the time of transplantation. PMID- 3085944 TI - Modified technique for percutaneous transfemoral pulmonary angiography. AB - Percutaneous transfemoral pulmonary arteriography was easily performed in 175 patients with a newly modified Grollman catheter developed to facilitate catheter passage through the tricuspid valve without a tip deflector. No significant catheter-related complications occurred. This simple technique allowed rapid and safe access to the pulmonary arteries. PMID- 3085945 TI - Flow-directed catheter for superselective arterial catheterization: an experimental evaluation. AB - A coaxial infusion catheter of 3 Fr Teflon and Gore-Tex was developed to facilitate superselective catheterization of cerebral arteries for the delivery of therapeutic agents. The catheter, technique for use, and preliminary results are described. PMID- 3085946 TI - Use of large silicone catheters in patients with long-term percutaneous transhepatic biliary drainage. AB - In 30 patients with inflammatory bile duct stenoses or slow-growing tumors of bile ducts, 12-18 F silicone catheters were placed with a percutaneous transhepatic approach in order to provide a more efficient and comfortable internal-external drainage. The main advantages were the large variety in size, improved flow, and softness of the catheter. However, because of the absence of distal tapering, the tubes had to be inserted several days after the initial drainage, when a tract was formed through the liver. PMID- 3085947 TI - Sciatic nerve block under fluoroscopic guidance. AB - Sciatic nerve block under fluoroscopic guidance was performed in 17 patients. This anesthetic technique along with femoral nerve block was found to be effective in patients having unilateral femoral arteriography or occlusive arteriography of their extremities. No complication was encountered in this group of patients. PMID- 3085948 TI - Thallium myocardial perfusion scintigraphy: influence of perfusion, scatter, and photon energy on the detection of lesions. AB - Experimental studies have been made of lesion detectability in myocardial perfusion studies using thallium-201. A series of images (AP view) was generated mathematically. Images were simulated with 100k, 200k, and 300k counts for the complete image and either non- or half-perfused lesions (lesion volume 1-6 1/2% of total myocardial volume). In addition thallium images were generated excluding scatter; images were also generated with a radiopharmaceutical using 140, 184 and 296 keV, assuming the biological distribution of thallium. All images were interpreted by seven observers. Count density did not affect the true-positive fraction of the interpretations. However, the false-positive fraction decreased significantly when count density increased. Lesions located far from the camera were detected worst. The intraobserved variability was largest for interpretation of these regions. Small lesions were poorly detected. Perfusion of lesions significantly affected their detection, independent of the count density, lesion volume, and lesion location. Scatter did not affect the detection of lesions. No significant difference was found when the performance of the observers was compared for 80 keV and 140 keV. The use of 184-keV and 296-keV photons resulted in a lower detection rate probably because of the use of a high energy collimator. PMID- 3085949 TI - Production of endothelium derived relaxant factor is dependent on oxidative phosphorylation and extracellular calcium. AB - The production (synthesis or release or both) of endothelium derived relaxant factor was studied in rabbit aortic strip preparations and an aortic-coronary artery bioassay system. Production of endothelium derived relaxant factor was rapidly inhibited by agents that inhibit mitochondrial electron transport or F1 ATPase, or which uncouple oxidative phosphorylation, but was only slowly impaired by inhibition of glycolysis. It was dependent also on the presence of extracellular calcium with a rapid on-off response time. This study shows that production of endothelium derived relaxant factor appears to be dependent on both oxidative phosphorylation and extracellular calcium. PMID- 3085950 TI - Effect of glyceryl trinitrate on peripheral arteries alters left ventricular hydraulic load in man. AB - Effects of sublingual glyceryl trinitrate (GTN) were studied in ten patients without heart failure during diagnostic cardiac catheterisation following angiography. GTN caused substantial reduction in peak left ventricular and aortic pressure (19 mmHg) with lesser reduction in mean aortic pressure (9 mmHg) and no change in diastolic aortic pressure. Reduction in stroke volume (by 15%), associated with fall in left ventricular end diastolic pressure (by 4 mmHg) was insufficient to explain the marked (17 mmHg - 34%) reduction in pulse pressure. Decrease in pulse pressure was associated with loss of the late systolic peak on both the aortic and left ventricular pressure wave. This peak is caused by pulse wave reflection. GTN caused no change in peripheral resistance or in indices of aortic compliance (characteristic impedance, total arterial compliance) but was associated with reduction in fluctuations of both modulus and phase of aortic impedance. All these changes in pressure waves and in impedance spectra are explicable on the basis of decreased peripheral wave reflection. This can be attributed to the known vasodilatory effect of GTN on the peripheral arteries. Simulation of arterial vasodilatation in a multi-branched model of the systemic arterial system confirmed this interpretation. Dilatation of peripheral arteries explains in part the beneficial effects of GTN in adult man. PMID- 3085951 TI - Calcium-induced calcium release mechanism from the sarcoplasmic reticulum in skinned crab muscle fibres. AB - Mechanically skinned skeletal muscle fibres of the crab Carcinus maenas have been used to investigate the mechanism of calcium release from the sarcoplasmic reticulum. Calcium release has been monitored by the amplitude and kinetics of the tension developed by the fibre. Results show that a very low calcium concentration, insufficient to directly activate contractile proteins, induces a release of calcium from the SR. This release is stimulated by low concentrations of caffeine and inhibited by small amounts of EGTA. Thus, a graded calcium induced calcium release mechanism dependent on extrareticular calcium concentration has been demonstrated in skinned crab muscle fibre. PMID- 3085952 TI - A speculative view of the multicomponent nature of T cell antigen recognition. PMID- 3085953 TI - c-fos expression is neither sufficient nor obligatory for differentiation of monomyelocytes to macrophages. AB - The c-fos gene is rapidly and transiently expressed when human U-937 and HL-60 leukemia cells are induced to differentiate to macrophages. We show that the expression of c-fos is controlled primarily at the transcriptional level. c-fos mRNA is very labile, with a half-life of less than 30 min. Superinduction of c fos in the presence of cycloheximide occurs primarily because of stabilization of c-fos mRNA. When U-937 cells are serum-stimulated or treated with diacylglycerol, a c-kinase agonist, c-fos is transiently expressed to high levels; however, the cells fail to differentiate to macrophages. Furthermore, HL-60 cell variants resistant to TPA can be induced to differentiate to macrophages in the absence of detectable c-fos expression. PMID- 3085954 TI - The muscle pattern of a segment of Drosophila may be determined by neurons and not by contributing myoblasts. AB - Each segment of Drosophila has a characteristic pattern of muscles. Like the segments of the cuticle and the central nervous system, the muscle pattern is ultimately dependent on the deployment of selector genes such as elements of the bithorax complex. We use nuclear transplantation to make genetic mosaics in which the donor, but not the host, is mutant for part of the bithorax complex. Making use of a muscle pattern that is found only in the male, we ask which cells have to be mutant in order to obtain mutant muscles and find that these crucial cells do not contribute to the muscles themselves. The evidence implicates neurons that innervate the muscles. Our hypothesis is that the sex and segmental identity of the motor or neurosecretory neurons determine the development of muscle pattern. PMID- 3085955 TI - Changes in the chromatin structure of Drosophila glue genes accompany developmental cessation of transcription in wild type and transformed strains. AB - Three Drosophila salivary gland glue genes show a dramatic transition in their DNAse I hypersensitive sites during the short period between the late third instar and the white prepupa, which correlates with the cessation of their transcription. In culture cells, where the genes are inactive, there is a chromatin configuration similar to that of prepupal salivary glands. In two transformed fly strains where the sgs3 gene is active at new chromosomal sites, including one in which 2.6 kb of sgs3 upstream sequences have been inverted, the same DNAase I hypersensitive sites and developmental transitions are seen over the same DNA regions. These results, together with the analysis of transformants carrying rearranged sgs3 genes, suggest that there is at least one distal DNAase I hypersensitive site associated with an element of regulation which may be exchanged between sgs genes. PMID- 3085957 TI - Heat shock regulatory elements function as an inducible enhancer in the Xenopus hsp70 gene and when linked to a heterologous promoter. AB - The Xenopus hsp70 promoter contains three copies of the consensus heat shock element (HSE) between positions -260 and -100. When the gene is transfected into mammalian cells, maximal heat-induced expression requires two HSEs in addition to a CCAAT box located next to the TATA box. The HSE-containing region can be separated from the CCAAT/TATA region without affecting expression of the gene, and it can enhance transcription of a linked beta-globin gene upon heat shock. It thus has the properties of a heat-inducible enhancer. Such an enhancer can also be generated by duplication of HSE sequences from the Drosophila hsp70 promoter, which were previously identified as an upstream promoter element and are known to bind a purified heat shock transcription factor in vitro. PMID- 3085956 TI - Regulation of very primitive, multipotent, hemopoietic cells by hemopoietin-1. AB - Hemopoietin-1 (H-1) is known to act synergistically with CSF-1, a mononuclear phagocyte growth factor, to induce the development of primitive hemopoietic cells. To determine whether purified H-1 also acts on multipotent hemopoietic cells, its ability to act synergistically with interleukin-3 (IL-3) and erythropoietin (Epo) was tested in methyl cellulose cultures of murine bone marrow cells. In the presence of IL-3, H-1 increased the number of colonies formed by primitive, multipotent cells by approximately 30-fold. H-1 alone or H-1 plus Epo produced no colonies. Forty percent of the colonies induced by H-1 plus IL-3 contained cells that could be subcultured at least twice, whereas cells from colonies induced by IL-3 alone could not be similarly subcultured. Thus H-1 permits CSF-1 or IL-3 to act on cells more primitive than those acted on by either growth factor alone. The results indicate that H-1 acts on the most primitive hemopoietic cells yet shown to proliferate and differentiate in culture. PMID- 3085958 TI - Resolution of linear minichromosomes with hairpin ends from circular plasmids containing vaccinia virus concatemer junctions. AB - The junctions, separating unit-length genomes in intracellular concatemeric forms of vaccinia virus DNA, are duplex copies of the hairpin loops that form the ends of mature DNA molecules present in infectious virus particles. Circular E. coli plasmids with palindromic junction fragments were replicated in vaccinia virus infected cells and resolved into linear minichromosomes with vector DNA in the center and vaccinia virus DNA hairpins at the two ends. Resolution did not occur when the concatemer joint was less than 250 bp or when plasmids were transfected into uninfected cells, indicating requirements for a specific DNA structure and viral trans-acting factors. These studies indicate that concatemers can serve as replicative intermediates and account for the generation of flip-flop sequence variation of the hairpins at the ends of the mature vaccinia virus genome. PMID- 3085959 TI - Clinical pharmacology of antibiotic agents. PMID- 3085960 TI - Immunoelectronmicroscopic localization of actin in ionophore-treated boar sperm. AB - Actin in ionophore-A23187 treated boar sperm has been localized by indirect immunofluorescence and immunoelectronmicroscopy (IEM), using an anti-actin monoclonal antibody. By IEM, after en bloc staining technique and treatment with 15 nm colloidal gold-IgM complex, actin was found associated with the plasma membrane (PM) and the outer acrosomal membrane vesicles and under the PM of the equatorial segment. PMID- 3085961 TI - Ofloxacin: bactericidal effect in an in vitro pharmacokinetic model. AB - Ofloxacin has been evaluated in an in vitro model where microorganisms were exposed to the varying concentrations met in human serum after the oral administration of a 200 mg dose. The recently isolated strains were selected with minimum inhibitory concentrations (MICs) representative of the MICs 90% of ofloxacin against the species considered. Results showed that ofloxacin sterilized the bacterial cultures of S. aureus, P. morganii and E. coli, with 99.99% of killing still evident for P. aeruginosa after 12 hours of exposure. All the reference compounds (amoxicillin 1 g b.i.d., cefaclor 500 mg t.i.d., rifampicin 450 mg b.i.d.) showed, in the same test, worse results than ofloxacin. PMID- 3085962 TI - Immunochemical evidences that hexachlorobenzene induces two forms of cytochrome P 450 in the rat liver microsomes. AB - Induction by hexachlorobenzene (HCB) of the liver microsomal system of metabolism of xenobiotics has been studied in comparison with the inductions by phenobarbital (PB) and 3-methylcholanthrene (MC). It has been shown that HCB increases the content of cytochrome P-450 in the microsomes. Like PB, HCB induces the activities of aminopyrine- and benzphetamine-N-demethylases. At the same time HCB increases also the activities of benzpyrenehydroxylase and 7-ethoxyresorufin O-deethylase, which are characteristic of the MC-induction. However, sodium dodecyl sulphate (SDS)-electrophoresis on polyacrylamide gel has revealed that HCB, similar to PB, induces protein with Mr = 52 000 (cytochrome P-450), but not the protein with Mr = 56 000, which is the main isoenzyme of cytochrome P-450 in MC-microsomes (P-448). Using specific antibodies to isolated cytochromes P-450 and P-448 (anti-P-450 and anti-P-448) it has been found by rocket immunoelectrophoresis that in HCB-treated microsomes 20% of the total cytochrome P-450 consist of PB-form and about 10% comprise cytochrome P-488. It has also been found that anti-P-448 totally inhibit 7-ethoxyresorufin-O-deethylase activity of HCB-microsomes while anti-P-450 was inactive. The data presented give direct proof that HCB exemplifies an individual chemical compound which is able to initiate the synthesis of both PB-form and MC-form of the cytochrome P-450. PMID- 3085963 TI - Inhibitory effect of glycyrrhetinic acid derivatives on lipoxygenase and prostaglandin synthetase. PMID- 3085964 TI - Modulation of mouse skin tumor promotion by dietary 13-cis-retinoic acid and alpha-difluoromethylornithine. AB - The effects of dietary supplementation of 13-cis-retinoic acid (13-cis-RA) and alpha-difluoromethylornithine (DFMO) in the drinking water on 12-O tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation was determined. Administration of 13-cis-RA in the diet and DFMO in the drinking water was started 1 week and 2 days before the first TPA application to the dimethylbenz[a]anthracene-initiated skin of either female CD-1 or SENCAR mice, respectively. Dietary 13-cis-RA failed to inhibit both the tumor yield and the incidence; papillomas per mouse at 0, 5, 50, 100 and 200 mg/kg diet 13-cis-RA doses were 25, 30, 22, 28 and 25 respectively at 18 weeks of promotion treatment and at all doses 100% of the mice bore papillomas. However, dietary 13-cis-RA dramatically reduced the size of skin tumor promoted with TPA. 13-Cis-RA at doses of 5, 50, 100 and 200 mg/kg diet inhibited skin papillomas (greater than 4 mm diameter) per mouse by 28, 55, 76 and 93%, respectively. Retinoid treatment did not affect body weight gains and the survival was more than 80% in all groups. In accord with our previous findings, DFMO when given in drinking water, was a very effective inhibitor of mouse skin tumor promotion by TPA; DFMO at 0.25% concentration inhibited the number of papillomas by 50%. Inhibition of skin tumor promotion by combined treatments with dietary 13-cis-RA (100 mg/kg) and DFMO (0.25%) in the drinking water was possibly additive. The retinoid and DFMO preclude TPA-increased ornithine decarboxylase (ODC) activity and the accumulation of putrescine by differential effects on ODC, an enzyme associated with skin tumor promotion by TPA. PMID- 3085965 TI - The disposition and in vivo covalent binding to liver DNA of the monoazodyes 6-(p dimethylaminophenylazo)benzothiazole (6BT) and 5-(p dimethylaminophenylazo)indazole (5I) after administration to the rat. AB - 6-(p-Dimethylaminophenylazo)benzothiazole (6BT) and 5-(p dimethylaminophenylazo)indazole (5I) comprise respectively a carcinogen/non carcinogen pair of monoazo dyes related to the hepatocarcinogen, butter yellow (DAB). While both members of the pair are potent bacterial mutagens in vitro, only 6BT induces unscheduled DNA synthesis in rat liver in vivo. To investigate factors responsible for these divergent activities we have determined in rats: relative rates of uptake from the gut after direct injection of 14C-labelled compound into intestine in situ, and after administration p.o.; distribution in selected tissues and elimination in urine, faeces and bile; binding of both compounds in vivo to liver DNA. The results revealed that, although 5I was taken up from the gut to a lesser extent than 6BT, comparable labelling associated with both compounds was detected in the presumed target organ (the liver). 5I binds in vivo to DNA much less effectively than 6BT. Therefore it would seem that other factors, such as differential metabolism in vivo, are more important than differences in uptake and distribution in accounting for the divergent activities of 6BT and 5I. PMID- 3085966 TI - Aflatoxin B1 binding to plasma albumin and liver DNA upon chronic administration to rats. AB - The hepatocarcinogen aflatoxin B1 (AFB1) was administered to male Wistar rats by oral intubation in either single or repeated doses and the binding to plasma protein and liver DNA determined. Twenty-four hours after a single dose (3.5-200 micrograms/kg AFB1) a constant ratio was found between levels of aflatoxin bound to plasma protein and that bound to liver DNA. In total 0.98-2.15% of the administered dose was bound to the plasma protein at this time point. In the chronic study rats received two doses of 0.5 microgram AFB1/day and groups of animals were killed on days 2, 3, 7, 14, 21 and 24. Binding of aflatoxin to plasma protein accumulated to a level 3-fold higher than that seen after a single dose. Levels of binding reached a plateau between days 7 and 14 of treatment and then remained stable until the end of the experiment. Binding to DNA also accumulated, 2.5-fold and in parallel to plasma protein, binding reached a plateau between days 7 and 14 of treatment. In both the chronic and acute studies fractionation of the plasma proteins by Sephadex G-200 chromatography showed that all detectable bound aflatoxin was associated with a single peak corresponding to albumin. Thus, a constant ratio was observed, after chronic or single exposure, between the concentration of plasma albumin-bound aflatoxin and that bound to DNA of the liver, the target organ for carcinogenesis by AFB1. In order to investigate the proposed role of AFB1 in the aetiology of primary hepatocellular carcinoma in man it would be of great value to have a method for assessing long term human exposure at an individual level. The relevance of the observations presented in this paper are discussed in the light of such a requirement. PMID- 3085967 TI - Selective interactions of cytochromes P-450 with the hydroxymethyl derivatives of 7,12-dimethylbenz[a]anthracene. AB - Competition between a hydroxylated metabolite and the parent polycyclic aromatic hydrocarbon (PAH) for metabolism at cytochromes P-450 may result in the generation of hydroxylated dihydrodiol epoxides. The effectiveness of the competition between 7-hydroxymethyl-12-methylbenz[a]anthracene (7HOMMBA) or 12 hydroxymethyl-7-methylbenz[a]anthracene (12HOMMBA) and 7,12 dimethylbenz[a]anthracene (DMBA) is highly dependent on the form(s) of cytochrome P-450 in the microsomes. The inhibitory effects of exogenously added 7HOMMBA or 12HOMMBA on DMBA metabolism were 30- to 50-fold greater in 3-methylcholanthrene (MC)-induced rat liver microsomes (Ki = 0.4 microM) compared to either uninduced or phenobarbital (PB)-induced liver microsomes (Ki = 14 and 11 microM, respectively). Similarly, product inhibition of total DMBA metabolism by metabolites generated in situ was significant only in MC-induced liver microsomes (Ki' = 2.5 microM). Metabolism of 7HOMMBA in these microsomes was strongly restricted by an unusual substrate inhibition derived from the inhibitory binding of a second molecule of 7HOMMBA. This same phenomenon was observed with reconstituted cytochrome P-450c but not with PB-induced or uninduced microsomes. Complex formation by binding of DMBA, 7HOMMBA, and 12HOMMBA to purified P-450c reconstituted in phospholipid micelles was determined by optical spectroscopy and fluorescence quenching. Binding affinities of both the 7HOMMBA and 12HOMMBA (Kd = 95 and 110 nM, respectively), were 2.5-fold higher compared to that of DMBA (Kd = 265 nM). These results provide a first demonstration that hydroxylation of a PAH can lead to preferential metabolism through an increased affinity for cytochrome P-450. PMID- 3085968 TI - In vitro early changes in intercellular junctions by treatment with a chemical carcinogen. AB - To examine early intercellular junction changes caused by treatment with 9,10 dimethyl-1,2-benzanthracene (DMBA), rat lingual epithelium was cultivated in isolation and observed by electrophysiological, freeze-fracture and whole-mount electron microscopy. Electrophysiological measurements showed a transient decrease in membrane potential of -10.2 mV 6 h after the treatment. It returned to almost the same level as that of the control group 1 day later. Six hours after treatment, input resistance decreased rapidly to 5.3 M omega but increased to 18.0 M omega 12 h after treatment. Transient reduction of input resistance and membrane potential occurred prior to the decrease in the coupling ratio 6 h after treatment with DMBA. In freeze-fracture replicas, the number of gap junctions decreased by approximately 45% of the control value 6 h after treatment with DMBA. At 12 h and thereafter, the number and area of gap junctions subsequently decreased by 60-80% of the control value. Alterations in the number and area of desmosomes were similar to those of the gap junctions. The formation of epithelial cytoskeletons, partially devoid of the 2-4 and 5-8 nm filaments was also observed. A decrease in the density of filament networks beneath the plasma membranes was especially apparent. Treatment with a carcinogen brought about morphological cellular changes as early as 6 h after treatment, and such early changes might trigger metabolic cellular abnormalities. Affected cells appear to move away from normal cells in a process of repeated destruction and revision of intercellular junctions, and cytoskeletons. PMID- 3085969 TI - Preferential binding of the carcinogen benzo[a]pyrene to DNA in active chromatin and the nuclear matrix. AB - Rat liver nuclei or hepatocytes were incubated with the proximate carcinogen, benzo[a]pyrene (BP) and its ultimate carcinogen, anti-benzo[a]pyrene-7,8-diol 9,10-epoxide (BPDE). Following carcinogen exposure, nuclei were fractionated by micrococcal nuclease digestion and stepwise extraction to yield an active chromatin fraction enriched in transcribed versus non-transcribed genes, a bulk chromatin fraction, a high-salt-extracted chromatin fraction and a nuclear matrix fraction containing elevated concentrations of transcribed and nontranscribed genes. BP binds more readily to DNA of active chromatin and nuclear matrix than to bulk chromatin. Since low concentrations of BPDE also selectively damage active chromatin and matrix DNA, selectivity is not due to the subnuclear location of enzymes which activate BP to BPDE. Higher BPDE concentrations cause more uniform DNA damage. Selective carcinogen attack may result from an accessible DNA conformation in active chromatin and matrix or from partitioning of carcinogen in the nuclear membrane. PMID- 3085970 TI - Comparison of hydrocarbon-DNA adducts formed in mouse skin in vivo and in organ culture in vitro following treatment with benzo[a]pyrene. AB - Species differences in the metabolism of toxic chemicals can confound the extrapolation of experimentally determined risk data to man. However, it is often difficult to obtain reliable information on human metabolism, particularly of genotoxic agents. In this study, comparisons of chromatographic profiles of DNA adducts formed in vivo and in vitro have been applied to develop and validate in vitro systems as models for the bioactivation of precursor genotoxic agents in vivo. Reversed phase h.p.l.c. analysis showed that the DNA adducts obtained from the skin (epidermal and dermal) of mice (CD1, CF1 and athymic nude mice) treated topically with [3H] or [14C]benzo[a]pyrene (BP) were qualitatively very similar to those formed in mouse (CD1) skin explant cultures. In each case the principal product was the N2-deoxyguanosine adduct, (+)-N2-(7R,8S,9R-trihydroxy-7,8,9,10 tetrahydrobenzo[a]-pyrene-10S- yl)-2'-deoxyguanosine, derived from (+)-7R,8S dihydroxy-9R,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. The use of [14C]BP has provided an accurate reference profile of BP-DNA adducts formed in mouse skin in vivo. These findings show that mouse skin explants maintained in organ culture effectively mimic the bioactivation of BP and the binding of the products to the DNA of mouse skin in vivo. Such culture techniques are readily transferable to human skin thus permitting the indirect determination of bioactivation pathways in human skin in vivo for comparison with those of mouse skin and other models used to determine the human hazard. In principle, this approach to validate in vitro bioactivation systems may be applied to all human tissues. PMID- 3085971 TI - DNA ligation and changes in chromatin structure associated with repair patches under conditions of inhibition of poly(ADP-ribose) synthesis. AB - The rate of intracellular ligation of excision repair patches has been measured under conditions of inhibition of poly(ADP-ribose) synthesis by 3-aminobenzamide. Excision repair patches in DNA of cells damaged by methyl methanesulfonate were labeled with [3H]thymidine and blocked at an intermediate stage by aphidicolin, an inhibitor of DNA polymerase alpha. Nearly half of the [3H]thymidine label in the repair patches was sensitive to rapid digestion by exonuclease III, indicating that the label was at unligated 3' termini of repair sites. Removal of [3H]thymidine and aphidicolin permitted the intracellular ligation rate to be determined. From analysis of chromatin, ligation appeared to occur rapidly, independent of the effect of 3-aminobenzamide. Analysis of purified DNA, however, indicated that high doses of methyl methanesulfonate resulted in slow ligation rates but that 3-aminobenzamide accelerated the rates of ligation. The analysis of chromatin, therefore, indicates that unligated repair sites are sites of protein accretion which block exonuclease III action. The results from analysis of DNA indicate that poly(ADP-ribose) synthesis and associated pool depletion inhibits ligation rates; 3-aminobenzamide prevents poly(ADP-ribose) synthesis, maintains pool levels high and facilitates rapid ligation. PMID- 3085972 TI - Fasting-induced dissociation of cationic and secretory events in pancreatic islets. AB - In pancreatic islets removed from 48 h-fasted rats, as distinct from fed animals, the release of insulin evoked by D-glucose is more severely impaired than that evoked by 2-ketoisocaproate. This decreased secretory response to D-glucose contrasts with an unimpaired cationic response to the sugar in terms of the glucose-induced decrease in both 86Rb and 45Ca outflow from pre-labelled islets. Likewise, fasting only causes a modest decrease of the secondary rise in 45Ca outflow evoked by D-glucose in islets perifused at normal Ca2+ concentration. The latter decrease appears more marked, however, if the cationic response to glucose is expressed relative to that evoked by 2-ketoisocaproate in islets removed from rats in the same nutritional state. It is concluded that, in the process of nutrient-stimulated insulin release, neither the decrease in K+ conductance (inhibition of 86Rb outflow) nor the sequestration of Ca2+ by intracellular organelles and/or direct inhibition of Ca2+ outward transport (decrease in 45Ca outflow) represent the sole determinant(s) of the subsequent gating of Ca2+ channels (secondary rise in 45Ca efflux). PMID- 3085973 TI - Effects of hydrocortisone on carbohydrase concentrations, de novo synthesis and turnover patterns in immature rat intestine. AB - Hydrocortisone administration to infant rats enhanced cellobiase and maltase activities and induced precocious expression of sucrase and trehalase activities along the length of the small intestine. These activity changes reflected proportional concentration increases in the enzymes lactase (EC 3.2.1.23), maltase/glucoamylase (EC 3.2.1.20) and sucrase-isomaltase (EC 3.2.1.48/10). Administration of an equivalent tracer dose of [3H]leucine (by body weight) to control and hydrocortisone-treated infant rats resulted in greater accumulation of label in the carbohydrase pools of the treated rats, suggesting their increased de novo synthesis. The increased concentrations of lactase and maltase/glucoamylase induced by exogenous hydrocortisone were matched by the presence of corresponding greater amounts of label in their brush border pools. Accumulation of label in each of the lactase, maltase/glucoamylase and sucrase isomaltase pools was generally similar in the hydrocortisone-treated rats, suggesting equivalent stimulation of their synthesis as a group by the humoral agent. The turnover rates of the carbohydrases as a group were found to be similar and did not appear to differ in control and hydrocortisone-treated rats. Total protein synthesis rates were slightly greater in the intestine of the hydrocortisone-treated group of rats. PMID- 3085974 TI - Some aspects of monoamine oxidase pharmacology. PMID- 3085975 TI - Regional myocardial volume perfused by the coronary artery branch: estimation in vivo. AB - Seven closed-chest dogs were anesthetized with intramuscular Innovar and a N2O/O2 gas mixture. Maximal coronary vasodilation was induced by intra-aortic injection of nitroglycerin (200 micrograms/kg) and continuous infusion of adenosine (1 mg/kg/min) into the main pulmonary artery. Superselective coronary arteriograms were obtained at varying distances along the left circumflex and left anterior descending coronary arteries during scans using the dynamic spatial reconstructor rapid tomographic x-ray scanner. At end-diastole the images of the coronary arteries and opacified myocardium were analyzed for cross-sectional area (CSA) of the coronary artery lumen and regional myocardial volume (Vdsr) perfused by that coronary artery. Postmortem regional myocardial volume (Vpath) was related to the volume perfused by the same artery measured in vivo by the dynamic spatial reconstructor as follows: Vdsr = 4.56 + 0.93 Vpath (r = .98, p less than .001). In addition, the cross-sectional area of the coronary artery supplying a volume of myocardium was related to that volume as follows: Vdsr = - 1.95 + 6.34 CSAmax (r = .88, p less than .001). This suggests that a maximally dilated coronary artery luminal cross-sectional area is linearly related to the volume of muscle it perfuses. We speculate that this relationship may be useful in expressing the physiologic significance of coronary arterial narrowing. PMID- 3085976 TI - The influence of preload and heart rate on Doppler echocardiographic indexes of left ventricular performance: comparison with invasive indexes in an experimental preparation. AB - We evaluated the ability of Doppler echocardiography to assess left ventricular performance in six open-chest dogs studied under various conditions. Intravenous infusions of nitroglycerin were used to vary preload, atrial pacing was used to control heart rate, and changes in inotropic state were induced by two different doses of dobutamine (5 and 10 micrograms/kg/min iv) and by administration of propranolol (1 mg/kg iv). Left ventricular anterior wall myocardial segment length was used as an index of preload. Maximum aortic blood flow, peak acceleration of aortic blood flow, and dP/dt were measured with an electromagnetic flow probe around the ascending aorta and a high-fidelity pressure transducer in the left ventricle. A continuous-wave Doppler transducer applied to the aortic arch was used to measure peak aortic blood velocity, mean acceleration, time to peak velocity, and the systolic velocity integral. The differences between mean values obtained under different inotropic conditions were significant at the p less than .01 level for peak velocity and at the p less than .05 level for mean acceleration. Within a given animal, Doppler measurements of peak velocity correlated very closely with maximum aortic flow (r = .96), maximum acceleration of aortic flow (r = .95), and with maximum dP/dt (r = .92). Mean acceleration measured by Doppler echocardiography also correlated very closely with conventional indexes, but was subject to greater interobserver variability. Doppler measurements of time to peak and the systolic velocity integral correlated less well with conventional hemodynamic indexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085977 TI - A new automated turbidimetric immunoassay for quantifying alpha 1-antitrypsin in serum. AB - This rapid, sensitive equilibrium turbidimetric immunoassay for quantification of alpha 1-antitrypsin involves a monospecific antibody, polyethylene glycol 6000 to accelerate and enhance the immunoprecipitation reaction, and Tween 20 surfactant to decrease and stabilize the sample-blank values. Turbidity at 334 nm is measured by an automated discrete analyzer. Grossly lipemic, icteric, or hemolyzed samples can be assayed. Correlation with results by radial immunodiffusion (RID) was excellent (r = 0.97, n = 84). Analytical recovery averaged 97.7 (SD 2.9)%. Within-run CVs ranged from 1.6 to 1.9%, between-day CVs from 2.0 to 3.5%. Reference values for healthy adults (n = 147) were determined by parametric estimation (for an assumed normal distribution of untransformed data). The lower limit (g/L) with its 0.90 confidence interval is 1.23 (range 1.18-1.28), the upper limit is 2.15 (2.10-2.20), and the mean is 1.69 g/L. PMID- 3085978 TI - Pseudohypoglycemia in a patient with Waldenstrom's macroglobulinemia, an artifact of hyperviscosity. PMID- 3085979 TI - More on the Amerlex kit analog method for thyroxin. PMID- 3085981 TI - Determination of indoxyl sulfate in plasma of patients with renal failure by use of ion-pairing liquid chromatography. AB - Using our newly developed ion-pairing reversed-phase liquid-chromatographic method for assay of indoxyl sulfate, we measured its concentration in plasma of normal subjects and patients in various degrees of renal failure. Response was linear over the range of 50 to 25 000 pmol of indoxyl sulfate injected into the chromatograph. We demonstrated the specificity of the assay for azotemic plasma by using enzymatic conversion with a sulfatase. For a moderately above-normal indoxyl sulfate concentration in azotemic plasma of 134 mumol/L (29 mg/L), the within-day CV was 1.6%, the day-to-day CV 2.8%. Mean analytical recovery was 101.0% (CV = 2.8%). Over a range of 29 to 192 mg of creatinine per liter of plasma (x), indoxyl sulfate (y) concentration (in mumol/L) was positively correlated (y = 1.30x + 0.43). This method should prove valuable for further study of uremic toxins. PMID- 3085980 TI - Apoprotein A-I measured by radial immunodiffusion in heparin-MnCl2 supernates. AB - We compared measurements of apoprotein A-I (apoA-I) in plasma and in heparin MnCl2 supernates analyzed by radial immunodiffusion. The apoA-I values were similar when the samples were fresh [n = 41, mean (SD), mg/L: plasma, 1393.4(349); heparin-MnCl2 supernates, 1364.9(332), p less than 0.01], but were greater than 8% lower in heparin-MnCl2 supernates after storage for seven days at 4 degrees C [plasma, 1348.0(351); heparin-MnCl2 supernates, 1237.6(342), p less than 0.001]. Neither heparin nor MnCl2 interfered directly with the immunodiffusion assay, and treating samples with tetramethylurea and urea to maximize the exposure of apoA-I did not prevent the decrease. MnCl2 (46 mmol/L) added to isolated HDL (d 1.063-1.21) decreased apoA-I values by 5.6% when measured immediately and by 16.7% after storage at 4 degrees C for seven days. High-density lipoprotein cholesterol values were unchanged by MnCl2. The results indicated that apoA-I was more stable in plasma than in heparin-MnCl2 supernates, probably because of an interaction between apoA-I and MnCl2. PMID- 3085982 TI - Immunoturbidimetric assays of apolipoproteins A, AI, AII, and B in serum. AB - In these immunoturbidimetric assays developed for apolipoproteins A, AI, AII, and B we used the Cobas-Bio centrifugal analyzer and commercially available antisera and calibrators. Within-day and within-run precision ranged from 1.0 to 5.8% for the four assays. The addition of bilirubin, up to 150 mg/L, or hemoglobin, 50 g/L, to sera did not interfere with the measurement of these apolipoproteins. Comparison of results of the immunoturbidimetric assays with those of radial immunodiffusion assays yielded slopes of 1.002, 0.822, and 0.957 and intercepts of -0.02, 0.47, and 0.03 g/L for apolipoproteins B, A, and AI, respectively. Reference intervals for the four apolipoproteins were determined by using sera from 193 apparently healthy individuals. PMID- 3085983 TI - Enzyme-linked immunoabsorbant assay of apolipoprotein AII in plasma, with use of a monoclonal antibody. AB - We produced a monoclonal antibody (C2-22) to human apolipoprotein (Apo) AII and describe its use in an enzyme-linked immunoabsorbant assay (ELISA) for Apo AII in human plasma and lipoprotein subfractions. No cross reactivity of the antibody with Apo CI, CII, CIII, E, or ablumin was detected. Apo AI and low- and very-low density lipoprotein cross reacted by 0.25%, less than 0.2%, and less than 0.3%, respectively. Whole plasma high-density lipoprotein (HDL) and HDL subfractions (HDL2 and HDL3) produced parallel displacement curves. This quantitative ELISA is based on competition between solid-phase-bound Apo AII and free Apo AII. Bound C2 22 is detected by alkaline-phosphatase-labeled second antibody. The standard curve for the assay is linear for plasma diluted 500-fold originally containing 140 to 1140 mg of Apo AII per liter. Delipidation of plasma samples exposed no additional antigenic sites. Within- and between-run CVs were respectively 8.4% and 8.7% at 327 mg/L of Apo AII, and 6.8% and 7.4% at 587 mg/L. Results correlated well with those by a polyvalent-antisera-based RIA procedure: r = 0.916, p less than 0.01, RIA = 0.896 ELISA -19.1 mg/L. PMID- 3085984 TI - Glycosaminoglycans of skin and urine in pseudoxanthoma elasticum: evidence for chondroitin 6-sulfate alteration. AB - Abnormally elevated hyaluronic acid and dermatan sulfate were isolated from lesional skin of a patient with severe pseudoxanthoma elasticum. These glycosaminoglycans (estimated as uronic acid) surpassed the normal controls by 33.6 and 4.8 magnitudes, respectively. Urine chondroitin 6-sulfate of the same patient moved faster by electrophoresis on cellulose acetate than its counterpart isolated from urine of another four patients or from the normal controls. Hyaluronic acid and chondroitin 6-sulfate exceeded their counterparts in normal urine by 2- to 10- and 4- to 18-folds, respectively. These increments correlated with the pseudoxanthoma elasticum severity in three of the five patients studied. The data showed: the first conclusive evidence that dermatan sulfate increased in lesional skin of a patient, with severe pseudoxanthoma elasticum, who also had considerably augmented HA, alteration of the same patient's urine chondroitin 6 sulfate, and diversified urine glycosaminoglycans in pseudoxanthoma elasticum. PMID- 3085985 TI - Pancreatic secretory trypsin inhibitor from human amniotic fluid and fetal and neonatal urine: concentrations and physicochemical characterization. AB - The levels and physicochemical properties of the pancreatic secretory trypsin inhibitor, also known as Kazal type trypsin inhibitor, were studied in human amniotic fluid. In the second trimester, the median concentration was 160 ng/ml, which exceeds the maternal serum levels 20-fold. Towards term, the amniotic fluid levels declined about 5-fold, whereas the maternal serum values remained constant. In fetal urine, the concentration of the trypsin inhibitor was similar to that in amniotic fluid in early gestation, whereas in newborn urine, the median level was 4-to 5-fold higher than in term amniotic fluid. The physiochemical characteristics of the trypsin inhibitor in amniotic fluid, neonatal urine and cancer urine from an ovarian cancer patient were similar, as studied by gel filtration, high performance reverse phase liquid chromatography, and complete immunological identity in immunodiffusion. The physicochemical similarity and levels in various compartments suggest fetal contribution to amniotic fluid levels of the trypsin inhibitor. PMID- 3085986 TI - Quantification of human serum apolipoprotein A-I by zone immunoelectrophoresis assay and a procedure for the preparation of an A-I standard. AB - A zone immunoelectrophoresis assay (ZIA) for human serum apolipoprotein A-I (Apo A-I) is described. In this immunologic technique, glass capillaries filled with agarose gel containing anti-Apo A-I are used. Apo A-I produces zones of immunoprecipitates with migration distances directly proportional to the apolipoprotein concentration. Two plasmas and their isolated high density lipoprotein (HDL) fractions, having different particle size distribution patterns have been analyzed for Apo A-I using rocket electroimmunoassay in parallel with ZIA. A good agreement between the two methods was obtained. With ZIA, Apo A-I complexed with lipids in HDL yielded concentration values that were unaffected by lipoprotein particle size and by delipidation. A standard curve, linear between 0.5 and 3.5 mg Apo A-I/1, was obtained with ZIA. A protocol for the preparation of an Apo A-I standard without prior purification of the apolipoprotein is presented. Using ZIA, 75 serum samples representing a heterogeneous study population were analyzed for Apo A-I. A mean value of 1.23 g/l with a relative standard deviation of 28% was obtained. The corresponding mean for total HDL cholesterol was 1.64 mmol/l (RSD = 61%). PMID- 3085987 TI - Myocardial chondroitin sulfates D and E in a case of acute carbon monoxide poisoning. AB - The glycosaminoglycans of the myocardium of an individual who died of acute carbon monoxide poisoning were quantified by two-dimensional electrophoresis on cellulose acetate membranes. The total glycosaminoglycan content was found to be approximately twice the normal value. In contrast to the content of each glycosaminoglycan of the normal heart, the level of the chondroitin sulfates of this patient's myocardium was found to be markedly increased whereas that of hyaluronic acid was decreased and dermatan sulfate could not be detected. Further, this tissue contained significant amounts of keratan sulfate and an oversulfated dermatan sulfate, glycosaminoglycans not found in normal myocardium. Of particular interest was the presence of two unusual oversulfated chondroitin sulfates (chondroitin sulfates D and E). PMID- 3085988 TI - Sulfogalactocerebroside and bis-(monoacylglyceryl)-phosphate as activators of spleen glucocerebrosidase. AB - Sequential extraction of human spleen membranes with sodium cholate and n-butanol removes endogenous lipids and renders glucocerebrosidase activity dependent upon exogenous acidic lipids (e.g., phosphatidylserine, gangliosides) and a heat stable activator protein (HSF). In the present report, we show that two previously untested lysosomal acidic lipids, namely sulfogalactocerebroside and bis-(monoacylglyceryl)-phosphate (BMP), also activate normal human glucocerebrosidase. In addition, sulfogalactocerebroside also markedly enhanced the activity of glucocerebrosidase isolated from a patient with type 1 (non neuronopathic) Gaucher's disease, resulting in a specific activity which was 60 80% that of control glucocerebrosidase. Furthermore, when the sulfolipid was used as the activator, glucocerebrosidase from the type 1 patient was 30 times more active than the corresponding glucocerebrosidase from a person with type 2 (neuronopathic) Gaucher's disease. In contrast, the two BMPs, one rich in C26 saturated fatty acid and another rich in C18 unsaturated fatty acids, were relatively poor activators of both mutant glucocerebrosidases while providing excellent reconstitution of control activity. PMID- 3085989 TI - Absorption of oral diphosphonate in normal subjects. AB - Absorption of the diphosphonate etidronate (HEDP) was measured in 20 volunteer subjects at two centres (Glasgow and Madison) using a new method based on simultaneous administration of HEDP and intravenous 99mTc-HEDP (Osteoscan). The mean absorption of HEDP in fasting subjects in Glasgow was 3.5% (range 1-8.9%) and in Madison 1.5% (0.7-2.8%) (P less than 0.035). In four subjects studies were repeated with good agreement between results (mean 3.9 cf. 3.5%). Six subjects had studies repeated when drug was ingested with food and in all cases absorption was effectively reduced to zero. We conclude that absorption of HEDP is significantly higher in normal subjects in Glasgow than in Madison. This may be of importance with regard to the finding of histological osteomalacia and fracture associated with HEDP use in Glasgow. PMID- 3085990 TI - Familial hypopituitarism associated with an enlarged pituitary fossa and an empty sella. AB - We report an 8-year follow-up of three sisters born of a consanguineous marriage and who originally presented with short stature and enlarged pituitary fossa. All have shown progressive failure of anterior pituitary hormone function. In addition, the two eldest sisters were eventually found to have an empty sella while the youngest, who initially showed an enhancing intrasellar mass consistent with a tumour, later showed an empty sella. A familial pituitary tumour developing early in childhood but subsequently undergoing involution could account for these findings. PMID- 3085991 TI - The effect of physiological changes in ovarian steroids on the prolactin response to gonadotrophin releasing factor. AB - This study was designed to assess the effect of an altered level of serum oestrogen and progesterone on the prolactin (PRL) response to gonadotrophin releasing hormone (GnRH). Six normal women were studied in the early follicular phase and the mid-luteal phase of one cycle and five menopausal women were studied before and after treatment with progesterone. Blood samples were collected at 15 min intervals for 6 h after a basal collection period of 30 min. Intravenous boluses of GnRH (1 microgram, 10 micrograms and 50 micrograms) were given at 0, 2 and 4 h. Basal samples were assayed for 17 beta-oestradiol (E2), oestrone (E1) and progesterone (P); LH, FSH and PRL were measured in all samples. Serum PRL was significantly elevated in all groups after 10 micrograms of GnRH with maximum increments (+/- SEM) ranging from 3.9 +/- 1.3 micrograms/l in early follicular phase women to 14.7 +/- 4.7 micrograms/l in progesterone-treated menopausal women. The PRL response to GnRH was significantly greater in the luteal phase and in menopausal women compared to early follicular phase women. There was a significant correlation between the maximum PRL response and the maximum LH response to GnRH in all the women studied (r = 0.7; P less than 0.01). A significant correlation was also found between the maximum PRL response and the basal serum oestrogen concentration in the normal cycling women (r = 0.8; P less than 0.01), but not when the menopausal women were included in the analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3085992 TI - Human serum thyrotrophin measurement by ultrasensitive immunoradiometric assay as a first-line test in the evaluation of thyroid function. AB - An ultrasensitive immunoradiometric assay (IRMA) using two monoclonal anti-TSH antibodies has been used for TSH measurements in basal conditions and after TRH stimulation. The results have been compared with those obtained by conventional radioimmunoassay (RIA). The IRMA method had very high sensitivity (0.07 microU/ml). Detectable serum TSH concentrations were found in all normal subjects by IRMA, but in only 76% by RIA. No overlap was observed with the results obtained by IRMA in untreated overtly hyperthyroid patients, in whom serum TSH was below the limit of detection. The relationship between basal and TRH stimulated serum TSH concentrations by IRMA and RIA was evaluated in 176 subjects including normals and patients with untreated and treated hyperthyroidism, functioning thyroid adenoma, nontoxic goitre and patients on L-thyroxine therapy. A normal TSH response to TRH was observed in virtually all patients with detectable basal serum TSH by both methods. When patients with undetectable basal serum TSH levels were considered, all but one (98%) had no TSH response to TRH by IRMA. On the contrary using RIA, an absent response was found only in 47% of subjects, a blunted responses in 10% and a normal response in 42%. These data indicate that basal serum TSH measurements by IRMA allows a complete discrimination of normal from hyperthyroid patients and can avoid the need for TRH stimulation tests. PMID- 3085993 TI - Studies of prolactin secretion in polycystic ovary syndrome. AB - In order to investigate the postulated relationship between hyperprolactinaemia and polycystic ovary syndrome (PCOS) we have studied 62 patients with PCOS. Only two patients had persistent prolactin (PRL) concentrations greater than the normal range on both random sampling and after blood sampling from intravenous cannula over 2 hours. Twenty-eight of the remaining patients had basal PRL secretion studied in more detail. Samples were collected at 15 min intervals during a 6 h period in all 28 patients and hourly samples were collected overnight from four patients. Results failed to demonstrate differences from control subjects in mean basal PRL concentrations, in spontaneous fluctuations or in increments related to stress, food or sleep. Lactotroph response to thyrotrophin releasing hormone, luteinising hormone releasing hormone and insulin stress testing in PCOS were determined. Results confirm a previous observation that normal PRL increments occur after ovulation and a blunted response follows a period of anovulation. This study has failed to find a consistent abnormality of lactotroph function in patients with PCOS other than that associated with anovulation. PMID- 3085994 TI - Selective reduction of elevated FSH levels in infertile men by pulsatile LHRH treatment. AB - In order to investigate whether isolated elevated FSH levels in men with idiopathic oligospermia can be lowered by pulsatile LHRH therapy, six patients were treated for 6 weeks with 5 micrograms LHRH pulses every 2 h. The pulses were delivered from a portable minipump (Zyklomat) through a subcutaneously inserted needle. At the end of treatment prepulse serum LH levels were no different from the levels before treatment while serum FSH was significantly reduced in all patients (16.9 +/- 2.5 U/l vs 11.3 +/- 1.9 U/l, mean +/- SEM; P less than 0.01). The normal FSH range was reached in one of the six patients. The areas under the LH curves following the first and the last (i.e. 504th) pulse were no different, while the areas under the FSH curves were significantly smaller (2870 +/- 434 vs 1776 +/- 237 U/l X min; P less than 0.01). Serum testosterone and oestradiol were significantly higher at the end of treatment (11.0 +/- 1.2 vs 15.2 +/- 1.9 nmol/l 146 +/- 18 vs 214 +/- 25 pmol, respectively). Thus increased FSH levels in men with idiopathic oligospermia can be selectively reduced by pulsatile LHRH treatment. If the increased FSH levels are not the result but rather a factor contributing to the pathogenesis of certain types of oligospermia these findings may have implications for the treatment of this condition. PMID- 3085995 TI - Endogenous luteinizing hormone surge in women during induction of multiple follicular development with pulsatile follicle stimulating hormone. AB - In this study nine consecutive normally cycling women undergoing in-vitro fertilization (IVF) were superovulated with clomiphene citrate followed by pulsatile 'pure' FSH injected s.c. via a pump (28 IU every 3 h). All women displayed an endogenous LH surge, which was markedly attenuated in most of the cases (peak value 44.5 +/- 5.9 U/l, duration 29.2 +/- 1.2 h, mean +/- SEM) as compared to spontaneous cycles. An increase in serum progesterone levels before the onset of the LH surge was seen in only one woman at a time when the LH values were low. During the LH surge serum progesterone levels increased significantly in all patients (12.7 +/- 1.90 nmol/l vs 4.74 +/- 1.57 nmol/l at the onset of the surge, mean +/- SEM, P less than 0.05) indicating follicular luteinization. Very high oestradiol levels in serum were found at the onset of the LH surge (7504 +/- 898 pmol/l, mean +/- SEM). Preovulatory oocytes were recovered from all women through a laparoscope 34-36 h after the beginning of the LH surge and embryos were replaced to them after IVF. One ongoing clinical pregnancy occurred. In contrast to results in monkeys, these results demonstrate for the first time that normally cycling women superovulated with clomiphene pulsatile 'pure' FSH will display an endogenous LH surge. Although the surge is attenuated implantation can occur. PMID- 3085996 TI - Inappropriate thyrotrophin secretion, increased dopaminergic tone and preservation of the diurnal rhythm in serum TSH. AB - A patient presented with mild hyperthyroidism, elevated serum T4 and T3, and an inappropriately raised serum thyrotrophin (TSH). There was no evidence of pituitary tumour (alpha-subunit secretion and CT scan of the pituitary were normal). The TSH response to TRH was greater than normal. The elevated TSH was suppressed by oral triiodothyronine (100 micrograms daily for 10 d). The normal diurnal variation of TSH was preserved. Intravenous injection of the dopamine receptor blocking agent domperidone led to a greater than normal elevation in TSH (maximum increments 18-20 mU/l). This increased dopaminergic tone was similar in studies carried out in the morning and late evening. The dopamine agonist bromocriptine (2.5 mg twice daily) failed to suppress serum TSH either acutely or over 6 weeks. The circadian rhythm was unaltered by this treatment. Basal serum prolactin levels were normal, and responded appropriately to TRH, domperidone and bromocriptine. These observations indicate that dopamine does not control the diurnal variation of TSH in nontumoral TSH-mediated hyperthyroidism. The increased dopaminergic tone demonstrated may be secondary to the primary failure of pituitary-thyroid feedback in the condition. PMID- 3085997 TI - Autonomous ovarian hyperfunction followed by gonadotrophin-dependent puberty in McCune-Albright syndrome. AB - A 5-year-old girl with the McCune-Albright syndrome presented with precocious puberty secondary to autonomously functioning ovarian cysts, followed by true central puberty. Progression from gonadotrophin-independent to gonadotrophin dependent precocious puberty may occur from elevated sex steroid levels leading to the early maturation of the hypothalamic-pituitary axis. PMID- 3085998 TI - Induction of ovarian activity by pulsatile infusion of LHRH in women with lactational amenorrhoea. AB - Four fully breast-feeding women at 6 weeks post partum were injected with LHRH (0.1 microgram/kg) every 94 min by pulsatile infusion pump. While follicular development occurred in all women, and evidence of luteinization was apparent in three out of four, normal ovulation and luteal function did not occur. This suggests that a simple disturbance in the pulsatile pattern of LHRH secretion may not, in itself, be enough to explain the suppression of ovarian activity during lactation. PMID- 3085999 TI - A divergence of plasma growth hormone response between growth hormone-releasing factor and insulin-induced hypoglycaemia among middle-aged healthy male subjects. AB - The capability of the anterior pituitary gland to secrete GH in response to an intravenous injection of growth hormone-releasing factor (GRF) and insulin induced hypoglycaemia was evaluated in 9 healthy male subjects ranging in age between 37 and 52 years old. Plasma GH response to 100 micrograms human GRF showed considerable intersubject variation and the increment of the peak value from the basal did not exceed 5 ng/ml in four out of 9 subjects. In contrast, insulin-induced hypoglycaemia resulted in a consistent stimulation of GH that exceeded 21 ng/ml in all subjects. The mean peak GH response after insulin induced hypoglycaemia was significantly higher than that after GRF (27.4 +/- 1.6 vs 10.6 +/- 1.9 ng/ml). These results demonstrate that a significant divergence exists in plasma GH responses between the two provocative tests in the middle aged subjects and suggest that the stimulation of GH following insulin-induced hypoglycaemia is not mediated solely by endogenous GRF. PMID- 3086000 TI - Hyperprolactinaemia in congenital hypothyroidism. AB - Serum prolactin concentrations were measured in nine untreated hypothyroid infants and 23 euthyroid controls. In the former group the serum prolactin concentrations were tenfold higher than the controls (352 vs 34 micrograms/l), declining gradually upon treatment. Although serum prolactin concentrations can be mildly elevated in adults with hypothyroidism, congenital hypothyroidism causes a profound and probably uniform hyperprolactinaemia; furthermore, the hormone concentration correlates directly with the simultaneous TSH concentration. The physiological importance, if any, of the hyperprolactinaemia in the fetus or neonate is uncertain. PMID- 3086001 TI - Control of the Bcg gene of early resistance in mice to infections with BCG substrains and atypical mycobacteria. AB - The effect of the Bcg gene on the early host response to intravenous infection with a variety of BCG substrains and some atypical mycobacteria was investigated. The numbers of live bacilli of BCG Pasteur and BCG Tice recovered from the spleens of Bcgs mice (C57BL/6, B10.A and BALB/c) at 3 weeks following infection exceeded the bacterial dose injected, whereas the number of CFU recovered from the spleens of Bcgr mice (A/J, DBA/2 and C3H/HeN) did not exceed the number of CFU injected, thus following the pattern observed in Bcgr mice and Bcgs infected with BCG Montreal. BCG Russia failed to multiply in both test groups; however, the number of CFU recovered in Bcgr mice was significantly lower than in Bcgs mice. On the other hand, the presence of live bacilli in the spleens of either Bcgr or Bcgs mice injected with BCG Japan was undetectable in most cases. Involvement of the Bcg gene in the early resistance to infection with BCG Pasteur, BCG Russia, Mycobacterium kansasii and M. intracellulare was documented by the significant differences in the kinetics of infections in mice of the C.D2 (BALB/c-Bcgr) and BALB/c (Bcgs) congenic lines. In BCG Russia, M. intracellulare and M. fortuitum infections, the phenotypic expression of the Bcg gene resulted in a more rapid elimination of the bacteria in the spleens of Bcgr when compared with Bcgs mice. On the other hand, the hepatic granuloma formation correlated with bacterial load except when C.D2 mice were infected with a small dose of BCG Pasteur or M. kansasii where extensive granulomatous hepatitis developed although no bacterial multiplication occurred in the spleen. It is suggested that granuloma formation could depend of the properties of the mycobacteria as well as the genetic background of the host without implicating the bacterial burden. PMID- 3086003 TI - The immunological consequences of gold therapy: a prospective study in patients with rheumatoid arthritis. AB - Gold sodium thiomalate (GST) is known to modify the disease process in patients with active rheumatoid arthritis (RA). To help understand the mechanism of action of GST, several immunological parameters were prospectively evaluated in 10 patients with active RA following the introduction of gold therapy. Before therapy, absolute numbers of peripheral blood T suppressor/cytotoxic lymphocytes were significantly depressed (P less than 0.01) and a raised T helper/T suppressor cell ratio was found. After 1 g of GST, an absolute reduction in total lymphocyte numbers including HLA/DR positive mononuclear cells, was evident (P less than 0.01). This lymphopenic effect was not selective for a single population since the proportions of T cells, T cell subsets and B cells remained unchanged. Lymphocyte function was also examined. Raised in vitro production of IgG (P less than 0.01) and IgA (P less than 0.05) was found before therapy. After GST, in vitro immunoglobulin synthesis was reduced and this was significant with respect to the IgM (P less than 0.001) and IgA (P less than 0.01) isotypes. Similarly, a parallel reduction in serum immunoglobulin levels developed. GST therapy was also associated with a reduced proliferative response to phytohaemagglutinin, concanavalin A and pokeweed mitogen in the initial phase of gold administration. The significant finding in this study suggest that the in vivo immunosuppressive effect of GST is explained not only by impaired mononuclear cell function but also by a significant reduction in T and B lymphocyte numbers. PMID- 3086002 TI - Mechanisms of macrophage activation in rheumatoid arthritis: the role of gamma interferon. AB - Gamma-interferon (gamma-IFN) is a potent inducer of surface expression of class II MHC molecules in vitro. Enhanced HLA-DR expression is a characteristic immuno histological feature of rheumatoid joints. To assess the possible relevance of gamma-IFN to macrophage (M phi) activation in rheumatoid arthritis (RA) we investigated the spontaneous and mitogen-induced production of gamma-IFN by RA lymphocytes using a sensitive radioimmunoassay. Synovial fluids (SF) from a variety of inflammatory and non-inflammatory rheumatic diseases did not contain measurable amounts of IFN. RA lymphocytes from peripheral blood (PBL) and joints failed to show spontaneous gamma-IFN production. RA and control PBL were equally responsive to both mitogen stimulation and to the addition of exogenous interleukin 2 (IL-2) as control PBL. SF lymphocytes from RA patients showed a significantly decreased PHA-stimulated gamma-IFN production and this was in contrast to the SF lymphocytes from patients with other inflammatory joint diseases who showed significantly increased gamma-IFN production compared with matched PB lymphocytes. These results show that gamma-IFN production by peripheral blood and joint cells from patients with RA is normal and it remains to be established whether gamma-IFN is the factor responsible for the macrophage activation seen in the disease. PMID- 3086004 TI - Acute tolerance to diazepam induced by benzodiazepines. AB - It was observed that the effectiveness of diazepam in causing sleep, as defined by the loss of righting reflex, was significantly decreased after a single exposure to either diazepam or lorazepam. RO 15-1788, a benzodiazepine antagonist, in contrast did not induce tolerance to diazepam. The mechanism for this acute tolerance is unclear. The rapidity in its development may exclude metabolic tolerance while alterations in brain sensitivity to diazepam remain a possibility. PMID- 3086005 TI - Acute tolerance to diazepam in mice: pharmacokinetic considerations. AB - The tolerance to the hypnotic effect of diazepam developed after a single exposure to diazepam in the presence or absence of cycloheximide, which blocks liver enzyme induction, was studied. At the high dose (30-35 mg/kg) used in this study, diazepam was found to be metabolized very rapidly in mice, consistent with previous findings using a much smaller dose (5 mg/kg). There was no significant difference in the pharmacokinetics of diazepam in control and tolerant mice as observed by monitoring the plasma and brain concentrations of diazepam and N desmethyldiazepam. It is concluded that acute tolerance to diazepam in mice may not be attributed to changes in pharmacokinetic factors. PMID- 3086006 TI - Mannitol potentiates cyclosporine nephrotoxicity. AB - A possible drug interaction between cyclosporine (CyA) and mannitol was tested for in female Wistar rats infused continuously with CyA 10 mg (40-50 mg/kg BW) in 24 ml mannitol 20% daily for 3 to 4 days (group CIM). For comparison, two other groups of rats were infused either with the same amount of CyA in 24 ml NaCl 0.9% (group CINa) or with the same amount of mannitol without CyA (group M). No animal of groups CINa or M, but 6 out of 10 group CIM rats developed severe oligo-anuric acute renal failure (ARF). Histologically massive vacuolisation of proximal tubular epithelia was found in the kidneys of CIM rats with ARF, while CIM rats without ARF showed minor to moderate degrees of vacuolisation. No vacuolisation was seen in groups CINa and M. Moderate amounts of tubular inclusion bodies and microcalcifications were detected in the kidneys of CIM rats without ARF and in those of CINa rats. To elucidate the mechanism of ARF, renal blood flow, creatinine clearance and proximal tubular pressures were measured in the kidneys of another series of CIM rats infused for 48-96 hours with CyA and mannitol. Renal blood flow and proximal tubular pressures in the kidneys of animals that had not or not yet developed ARF did not differ from those in rats infused with mannitol alone despite histological alterations with minor to moderate degrees of vacuolisation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086007 TI - Chronic cyclosporine A treatment reduces prostaglandin E2 formation in isolated glomeruli and papilla of rat kidneys. AB - Immunoreactive prostaglandin E2 (PGE2) formation of rat renal papilla and isolated glomeruli was determined following chronic cyclosporine A treatment (25 and 50 mg/kg BW/daily for up to 6 weeks). Additionally, the in vitro production of PGE2 and the release of C14-labelled arachidonic acid (AA) products were evaluated in the presence of increasing doses of cyclosporine A (CyA). Renal papillary slices and glomeruli were incubated in Krebs-Ringer-Buffer (KRB) at 37 degrees C under air conditions. PGE2 and C14-labelled AA-metabolites were determined in the incubation medium. Chronic in vivo CyA treatment reduced in vitro renal papillary PGE2 formation significantly. Furthermore, the conversion of AA to PGE2 by isolated glomeruli was significantly lower in rats pretreated with CyA over three weeks. In addition, the stimulatory effect of furosemide on PGE2 formation by isolated glomeruli was impaired following an in vivo CyA treatment for three weeks. In vitro incubation of CyA with renal papilla had no effect on in vitro PGE2 formation or the release of C14-labelled AA-metabolites. The data demonstrate that chronic in vivo treatment with CyA can reduce renal PGE2 formation. This effect might influence PG mediated renal functions. PMID- 3086008 TI - A surgical approach to the problem of severe lateral instability at the ankle. AB - A unified approach to ligamentous instability of the lateral side of the ankle was investigated in 100 ankles of 81 patients (age range, ten to 59 years). The approach consisted of augmentation of the collateral ligament system by means of the anterior portion of the peroneus brevis passed forward through the fibula and secured to the talocalcaneal interosseous ligament. In addition, torn ligaments were repaired or tightened in some cases. One hundred seven operations were performed between 1977 and 1983. Ninety-seven ankles were restored to clinical stability; 83 ankles were essentially asymptomatic. All three ankles that did not ultimately stabilize were in adolescent girls with chronic instability, one of whom was treated by three procedures. Of the remaining five repeat procedures, four had been adolescent girls initially treated for chronic ankle instability. PMID- 3086009 TI - Bi- and trimalleolar ankle fractures operated with nonrigid internal fixation. AB - The results of bi- and trimalleolar fractures treated with nonrigid internal fixation were analyzed in 134 patients. The fractures were of both pronation and supination type. The operative success was evaluated in terms of congruency as seen on the post-operative radiographs. The congruency was classified as either congruent, small, or grave displacement respectively. At follow-up evaluation, four variables were recorded: a linear analogue scale, an ankle score, range of motion, and presence of osteoarthritis. Fifty percent had congruent joints, 20% had small, and 30% had grave displacements. At follow-up examination those with congruent joints had significantly better function than those with displacements in all four variables. There were only minor differences between the two displacement groups. The nonrigid technique seems inadequate in retaining congruency of the unstable bi- and trimalleolar fractures. Congruency is the key to good prognosis. Even minor displacement significantly increases the risk of impending disability. PMID- 3086010 TI - Bone banking. A cost effective method for establishing a community hospital bone bank. AB - Both cost effectiveness and safety can be realized in the operation of a community bone bank by adoption of the following measures: deep freezing, rather than freeze drying; allogenic bone is collected from femoral heads excised from total hip arthroplasties; and careful donor and graft selection controls ensure an allograft free of disease which can be transmitted to the recipient. Two-year follow-up data reveal no complications or infections from implantation of 101 allografts. PMID- 3086011 TI - Diagnosis of a primary non-Hodgkin's lymphoma of the central nervous system by examination of the cerebrospinal fluid. AB - This paper is a report on a case of primary Non-Hodgkin's lymphoma of the central nervous system, diagnosed by cytological and immunological examination of the cerebrospinal fluid. The relevant literature on the subject is reviewed. The importance of examination of the cerebrospinal fluid in cases suspected of this disease is stressed. PMID- 3086012 TI - Spontaneous abortion. AB - Sporadic spontaneous abortion has been accorded relatively little scientific attention but has widespread prevalence and great personal impact. The physician must be continually vigilant to consider possibilities for Rh0(D) sensitization and offer prophylaxis when appropriate. The most immediate problems include differential diagnosis, haemorrhage, and infection, while later issues focus on counselling and subsequent pregnancies. Serious physical and psychological morbidity can be averted by the conscientious care of couples experiencing spontaneous pregnancy loss. PMID- 3086013 TI - Surgical techniques of uterine evacuation in first- and second-trimester abortion. AB - Induced abortion is an ancient procedure. Vacuum curettage is a recent innovation and is demonstrably superior to other methods for first-trimester abortions. Patient selection, patient preparation and the necessary instruments are described. The only absolute contraindications for local anaesthesia, vacuum curettage abortions are pregnancies too far advanced and allergy to local anaesthestics. The only mandatory laboratory tests are Rh blood group and cervical culture for gonorrhoea. Rh-negative patients must receive anti-D (Rh0) immunoglobulin. Perioperative antibiotics are of proven benefit. The technique of first-trimester vacuum curettage is described in detail here. The technique for very early abortion with the Karman cannula is also described. Fresh examination of tissue is critical after any abortion in order to rule out incomplete or missed abortion and to detect ectopic or molar pregnancy. Management of suspected perforation, haemorrhage, post-abortal syndrome and failed abortion are described. Dilation and evacuation (D&E) is the safest technique for mid trimester abortion, especially when performed at 13-16 weeks. Some mid-trimester techniques are reviewed and the technique we follow is described in detail. Laminaria tents are left in place overnight, and the procedure is performed under paracervical block with intravenous sedation using low doses of diazepam and fentanyl. Evacuation is by means of large-bore vacuum cannula system and large ovum forceps. General anaesthesia is avoided because it increases the risk of perforation and haemorrhage. Adjuncts to D&E are described: intraoperative real time ultrasound, intracervical vasopressin, two days' treatment with laminaria tents, and Hern's technique combining laminaria with intra-amniotic infusion of urea prior to D & E. PMID- 3086014 TI - Grouping of Aspergillus species with exoantigens. AB - Ninety-two slant extracts prepared from 2-week-old cultures of seven Aspergillus groups, nonsporulating "albino-type" A.fumigatus, Blastomyces dermatitidis, Histoplasma capsulatum, 3 Penicillium spp., 2 Pseudallescheria spp., 3 Paecilomyces spp., and Acremonium sp., were analyzed concurrently against antisera to A. fumigatus, A. flavus, A. nidulans, A. niger, and A. terreus. The extract of each of the aforementioned five pathogenic Aspergillus spp. produced 2 11 specific antigen-antibody complexes after reacting with its homologous antiserum. Antisera prepared against extracts to these pathogenic aspergilli demonstrated variable intra-generic crossreactivity, which were eliminated by adsorption with heterologous Aspergillus spp. antigens. Fewer nonspecific reactions were noted with the reference antigen-antibody precipitates of A. nidulans and A. Terreus than with reference precipitates of the other Aspergillus spp. Exoantigen extracts of "albino-type" isolates of A. fumigatus produced two to five specific precipitins against anti-A. fumigatus serum only. Based on the specific reactions produced by the eight albino-type isolates and 1 Aspergillus sp. isolate, all these fungi were identified correctly and placed in the A. fumigatus group. Analyses of conventionally identified A. fumigatus, A. flavus, A. nidulans, A. niger, and A. terreus including an isolate of A. parasiticus, enabled us correctly to classify them (51/51, or 100%) into their respective groups. Specific Aspergillus spp. antigen-antibody precipitates were characterized and used as references in exoantigen tests. None of the fungi in the genera other than Aspergillus produced antigens identical to the selected reference antigens. PMID- 3086015 TI - Cell surface phenotype of the spontaneous immunoglobulin-secreting cells in peripheral blood from homosexual men with generalized lymphadenopathy or AIDS. AB - Activated B cells that spontaneously secrete immunoglobulin are found in homosexual men with AIDS or lymphadenopathy. These cells constitute a very small percentage of peripheral blood lymphocytes (usually less than 1%), making identification of their surface antigens difficult. To identify surface antigens on immunoglobulin-secreting cells, peripheral blood mononuclear cells were first reacted with monoclonal antibody, followed by a fluorescein-conjugated goat antimouse globulin reagent. Secretion of immunoglobulin was then assessed in a reverse hemolytic plaque assay, with a modified Cunningham chamber in which an individual plaque-forming cell could be examined with a fluorescence microscope. All plaque-forming cells were found to be reactive with OKT 10 and 4F2 monoclonal antibodies; there was moderate reactivity with anti-la and B4. The same results were found when normal pokeweed mitogen-stimulated lymphocytes were tested. The surface phenotype of these cells is consistent with that of a preplasma cell. PMID- 3086016 TI - Immunologic complexity of lymphoblastic lymphoma. AB - Twelve patients with a histologic diagnosis of lymphoblastic lymphoma (LBL) were studied immunologically using the methodologic refinement of comparative serial section immunochemistry. By this means, we demonstrate complex LBL phenotypic profiles, revealing 3 major immunologic subtypes: immature T cell, 7 cases; intermediate or mature T cell, 3 cases; immature B cell (pre-pre-B), 2 cases. This phenotypic diversity challenges the basic belief that all LBL are the same. Our immature T-cell cases with frequent simultaneous Leu 2/3/6/9/CALLA/Tdt expression correspond to cortical thymic phenotypes; our mature T-cell phenotypes with Leu 9/la expression and absent L6/Tdt correspond either to medullary thymocytes or post-thymic T cells; our pre-pre-B phenotypes with simultaneous Tdt/CALLA/B4 expression correspond to common acute lymphocytic leukemia (ALL) phenotypes. Mature T-LBL phenotypes are similar to "novel" peripheral T-cell lymphoma phenotypes. Scant or absent Tdt expression in mature LBL is not an isolated antigenic change but a complete phenotypic profile difference from immature T-LBL. The major T- and B-cell phenotypes of LBL might have therapeutic significance. Treatment among LBL phenotypes may need to vary as with acute lymphocytic leukemia phenotypes. Further study is needed; in the meantime, comparative serial section immunotyping promises substantial utility in revealing the immunologic complexity of the lymphomas. PMID- 3086017 TI - Juvenile xanthogranuloma of the iris managed with superficial radiotherapy. AB - A case of juvenile xanthogranuloma involving the iris successfully managed with superficial radiotherapy is presented. A review of the literature suggests that this benign condition, if progressive or extensive, is optimally treated with radiotherapy as an alternative to major surgical procedures, including enucleation. PMID- 3086018 TI - The molecular basis of autoimmunity. PMID- 3086019 TI - Calculation of the VD/VT ratio by the helium washout technique. AB - In four normal subjects and 51 patients with chronic bronchitis-emphysema, bronchial asthma and pulmonary fibrosis, the VD/VT ratio was measured by a helium washout technique (wVD/VT) and by the conventional Bohr's method using the arterial CO2 tension (VD/VT). In 16 patients the wVD/VT ratio was compared with that calculated from Bohr's equation with the alveolar CO2 tension measured by the rebreathing technique (AVD/VT). It was found that the values for the VD/VT ratio obtained by the helium washout technique were very close to those obtained by the conventional method using the PaCO2 or PACO2 values. PMID- 3086020 TI - Glucose oxidation rates in newborn infants measured with indirect calorimetry and [U-13C]glucose. AB - Indirect calorimetry and primed constant infusion of [U-13C]glucose were combined in 16 appropriate-for-gestational age newborn, parenterally fed infants, in order to measure glucose utilization and glucose oxidation respectively. Glucose intake ranged between 10.0 and 24.1 g day-1 kg-1 and energy intake between 156.9 and 439.3 kJ day-1 kg-1. Glucose utilization (P less than 0.001), glucose oxidation (P less than 0.001) and metabolic rate (P less than 0.005) increased significantly with rising glucose intake. The significant difference between glucose utilization and oxidation (P less than 0.001) can be accounted for by an increasing storage as fat. As lipogenesis from glucose consumes 15-24% of the original glucose energy, the increasing metabolic rate accompanying rising glucose intake is probably due to increasing lipogenesis. PMID- 3086021 TI - Effects of chronic uraemia on the formation of glucose and urea plus ammonia from L-alanine, L-glutamine and L-serine in isolated rat hepatocytes. AB - The effects of chronic uraemia on glucose production and nitrogen release (urea plus ammonia formation) from alanine, glutamine or serine in isolated rat hepatocytes were studied. Uraemia increased the rate of formation of urea plus ammonia from all three amino acids by 38-93% when they were present at a final concentration of 10 mmol/l. At lower concentrations (2 mmol/l) the rate of nitrogen release was not significantly increased. Hepatocytes from normal rats whose food intake had been restricted to the level of that of uraemic rats did not show the increased rates of nitrogen release. The increased rates of nitrogen release with hepatocytes from uraemic rats were not accompanied by increased rates of glucose synthesis. Instead, accumulation of metabolic intermediates occurred: lactate and pyruvate (alanine or serine as substrates) and glutamate (glutamine as substrate). Livers of uraemic rats had increased activities of glutaminase (30%) and serine dehydratase (100%). Hepatocytes from normal rats treated with phlorhizin to increase the plasma glucagon/insulin ratio behaved in a similar manner to hepatocytes from uraemic rats. They had increased serine dehydratase activity, and increased rates of utilization of serine or glutamine. The possible implications of these findings for human uraemia are discussed. PMID- 3086022 TI - Ventilatory sensitivity to inhaled carbon dioxide around the control point during exercise. AB - Rapid steady-state CO2 responses were determined in five normal adults at rest and at up to six levels of exercise by injecting pure CO2 at a constant flow into the inspiratory limb of a breathing circuit. Ventilation (V) was measured with a dry gas meter and PCO2 at the mouth was recorded by a mass spectrometer. Mean alveolar PCO2 (PACO2) was taken as equal to end-tidal PCO2 at rest, and during exercise was derived graphically from the sloping alveolar plateaus. The accuracy of the latter method was checked in separate experiments against arterial PCO2 (PaCO2). The mean results showed a linear relationship between change in PACO2 and change in V for work loads ranging from rest to 75 W (r = 0.94-0.98). Above 75 W the response became concave down with an initial essentially isocapnic phase. This suggests that during exercise there is a large increase in CO2 sensitivity about the control point. PMID- 3086023 TI - Evidence for adaptive diet-induced thermogenesis in man during intravenous nutrition with hypertonic glucose. AB - This study was designed to investigate the thermogenic effect of intravenously administered nutrition with glucose (given a fixed nitrogen intake of 12.5 g daily as amino acids) as the principal source of energy. The protocol was designed so that each patient received their energy intake in five consecutive periods of 3 days with intakes ranging from 6650 to 17,100 kJ/day with increments or decrements of 2600 kJ. Thermogenesis from administered glucose was evident between levels of energy supply of 6650 kJ/day and 17,100 kJ/day. The progressive rise in oxygen consumption and carbon dioxide production accounted for a total of 31% of the additional glucose which was administered. The net rate of fat synthesis from glucose reached a maximum 147 g/day at an energy supply of 14,500 kJ/day. This study suggests that both fat synthesis and the associated obligatory thermogenesis is the main component of diet-induced thermogenesis in response to glucose intakes in excess of 150 kJ day-1 kg-1. If the energy cost of fat synthesis (fat associated obligatory thermogenesis) is taken to be 22% of the total energy of the increase in glucose supplied, then only 9% (31-22%) of the glucose can be accounted for by adaptive thermogenesis. PMID- 3086024 TI - Lactulose, 51Cr-labelled ethylenediaminetetra-acetate, L-rhamnose and polyethyleneglycol 400 [corrected] as probe markers for assessment in vivo of human intestinal permeability. AB - The urinary excretion of lactulose, 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), L-rhamnose and polyethyleneglycol 400 (PEG-400) has been measured after intravenous and oral administration in healthy volunteers. Intestinal permeation of the probes was compared after their ingestion in iso-osmolar, hyperosmolar and cetrimide-containing test solutions. Urinary recovery of lactulose and 51Cr-EDTA after intravenous administration reached 75% by 5 h, and exceeded 90% at 24 h, and these values were 62 and 72%, respectively, for L rhamnose. Recovery of PEG-400, however, varied with the relative molecular mass (Mr) of each polymer from 25.9 to 68.5% in 24 h. Intestinal permeation of ingested lactulose and 51Cr-EDTA was low, but that of L-rhamnose was 45-fold, and that of PEG-400 100-fold, greater. Permeation of lactulose and 51Cr-EDTA was markedly increased by cetrimide and hyperosmolar stress, whereas that of L rhamnose showed little change. PEG-400 permeation was not affected by cetrimide, but was slightly increased by hyperosmolar stress. The 5 h permeation of lactulose, but not of L-rhamnose or PEG-400, correlated with that of 51Cr-EDTA (r = 0.98, P less than 0.001). These findings are compatible with three distinct pathways of unmediated mucosal permeation, L-rhamnose (radius less than 0.4 nm) passing mainly through small aqueous 'pores' of high incidence, lactulose and 51Cr-EDTA (radius greater than 0.5 nm) through larger aqueous 'channels' of low incidence susceptible to cetrimide and hyperosmolar stress, and PEG-400, which has appreciable lipid solubility, by partition through cell membrane lipid as well as the aqueous 'pores'. PMID- 3086025 TI - [Hypoprolactinemia in subjects with various pathologies of the reproductive system]. PMID- 3086027 TI - Comparison of culture, cytotoxicity assays, and enzyme-linked immunosorbent assay for toxin A and toxin B in the diagnosis of Clostridium difficile-related enteric disease. AB - Clostridium difficile culture, test tube, and microtiter cytotoxicity assays, and enzyme-linked immunosorbent assays (ELISAs) for toxin A and toxin B, were simultaneously performed on 113 fresh diarrheal stool specimens randomly selected from those submitted to our clinical laboratory for routine C. difficile testing. The performance of these tests in diagnosing C. difficile-related enteric disease (CDRED) was based on a clinical assessment of the likelihood of CDRED as determined by a systematic review of case histories blinded from the test results. Among 61 antibiotic recipients, both the microtiter cytotoxicity assay and the toxin A ELISA were highly specific for CDRED (95% and 100%, respectively). Specificities for the other procedures were much lower (tube cytotoxicity assay, 79%; culture, 74%; and toxin B ELISA, 56%). The high sensitivities of the culture (89%) and toxin B ELISA (83%) were somewhat negated by their low specificities. The only test that was both specific and had acceptable sensitivity (78%) was the microtiter cytotoxicity assay. This study indicates that ELISAs for detection of C. difficile toxins are not as reliable as the cytotoxicity assay in the laboratory diagnosis of CDRED, and that clinical correlation is essential in the evaluation of any new test for CDRED. PMID- 3086026 TI - In vitro inhibitory and bactericidal activity of cefpiramide and seven antipseudomonal agents against Pseudomonas aeruginosa. AB - Cefpiramide was tested against 493 clinical isolates of Pseudomonas aeruginosa and the results of minimal inhibitory concentration, minimal bactericidal concentration, bactericidal rate, and time-kill synergy studies were compared with those obtained with seven other antipseudomonal agents. The minimal inhibitory concentrations of cefpiramide for P. aeruginosa were comparable to all of the agents tested. Minimal bactericidal concentration results were generally within one twofold dilution of the minimal inhibitory concentration values for all agents tested. Bactericidal rate studies showed that at concentrations of four times the minimal inhibitory concentration, all of the agents produced rapid killing. Results of time-kill synergy studies showed a marked synergistic interaction between cefpiramide and each of three aminoglycosides, gentamicin, tobramycin, and amikacin. These results suggest that cefpiramide may be useful in the therapy of infections due to P. aeruginosa. PMID- 3086028 TI - Comparative study of four arginine ester hydrolases, ME-1, 2, 3 and 4 from the venom of Trimeresurus mucrosquamatus (the Chinese habu snake). AB - Four arginine ester hydrolases, ME-1, 2, 3 and 4 from the venom of Trimeresurus mucrosquamatus had been isolated and characterized by Sugihara et al. (1980, 1981, 1982, 1983). Immunologically, ME-1, 2, 3 and 4 are identical. The four enzymes hydrolyzed Pro-Phe-Arg-MCA and z-Phe-Arg-MCA. Furthermore, ME-2 slightly hydrolyzed Boc-Val-Pro-Arg-MCA, Boc-Phe-Ser-Arg-MCA and Boc-Ile-Glu-Gly-Arg-MCA. ME-1 cleaved almost simultaneously the Arg(22)-Gly(23) and Phe(25)-Tyr(26) bond of oxidized insulin B chain. ME-2 and 3 also hydrolyzed the same bond of insulin B chain, but the activity was not as potent as ME-1. ME-4 did not cleave the substrate. The four enzymes hydrolyzed C-terminal of arginine in the biologically active peptides. Four arginine ester hydrolases showed fibrinogenolytic activity. ME-1 and 2 first cleaved B beta-chain and then A alpha-chain. On the contrary, ME 3 and 4 cleaved A alpha- and B beta-chain simultaneously. The four enzymes also hydrolyzed fibrinogen in plasma cleaving B beta- and gamma-chain and slightly digesting A alpha-chain. The various inhibitors affected TAME (tosyl-arginine methylester) and the fibrinogen hydrolytic activity of the four enzymes. All four enzymes had fibrinolytic activity. PMID- 3086029 TI - Some special characteristics of glycogen synthase from chicken liver. AB - An anomalous initial grade of activation is observed for glycogen synthase from chicken liver when it is compared with synthase from mammalian liver. Some possible experimental causes for this discrepancy are investigated as well as the possibility of a different development stage to explain the special behaviour of avian synthase. It is concluded that avian synthase is less affected by external treatment than mammalian synthase. Avian synthase is always highly active, independently of external conditions and of development stage. PMID- 3086030 TI - Purification and characterization of purple acid phosphatase from rat bone. AB - An acid phosphatase, which was immunochemically identical to splenic purple acid phosphatase, was purified to homogeneity from rat bone. The enzyme was a two iron containing monomeric glycoprotein with a mol. wt of 36,000. The enzyme hydrolyzed aryl phosphates, nucleoside di- and triphosphates, thiamine pyrophosphate, phosphoenolpyruvic acid and acidic phosphoproteins. The enzyme was inhibited by ammonium molybdate, NaF and CuSO4 but not by tartrate and SH-reagents. PMID- 3086031 TI - Sodium cromoglycate: effects on allergic patch test reactions. PMID- 3086032 TI - Variability of resting energy expenditure in healthy volunteers during fasting and continuous enteral feeding. AB - The magnitude of variability in resting energy expenditure (REE) during the day was assessed in nine healthy young subjects under two nutritional conditions: 1) mixed nutrient (53% carbohydrate, 30% fat, 17% protein) enteral feeding at an energy level corresponding to 1.44 REE; and 2) enteral fasting, with only water allowed. In each subject, six 30-min measurements of REE were performed using indirect calorimetry (hood system) at 90-min intervals from 9 AM to 5 PM. The mean REE and respiratory quotient were significantly (p less than .01) greater during feeding than during fasting (1.08 +/- 0.07 [SEM] vs. 1.00 +/- 0.06 kcal/min and 0.874 +/- 0.007 vs. 0.829 +/- 0.008 kcal/min, respectively). Mean postprandial thermogenesis was 4.9 +/- 0.4% of metabolizable energy administered. The intraindividual variability of REE throughout the day, expressed as the coefficient of variation, ranged from 0.7% to 2.0% in the fasting condition and from 1.2% to 4.1% in the feeding condition. There was no significant difference between the REE measured in the morning and that determined in the afternoon. PMID- 3086033 TI - Prognostic factors in hyperglycemic hyperosmolar nonketotic syndrome. AB - Twenty-four patients suffering hyperglycemic hyperosmolar nonketotic syndrome were studied retrospectively to define initial prognostic factors. Twenty percent of these elderly patients (mean age 76 +/- 4.6 yr) had no history of diabetes, and only 54% experienced coma, which was not related to the level of plasma osmolality or to final outcome. The overall mortality was 46%, but death was directly related to nonmetabolic disorders in 64% of cases. Age; sex; acute precipitating factors (except precipitating drugs); admission levels of serum sodium, serum potassium, blood glucose, plasma osmolality, and serum creatinine; and insulin, macromolecular, and total fluid volumes infused during the first 24 h in the ICU were not related to death. The simplified acute physiology score was approximately the same for both survivors and nonsurvivors. PMID- 3086034 TI - Determinants of alveolar ventilation during high-frequency transtracheal jet ventilation in dogs. AB - The effectiveness of transtracheal jet ventilation is a function of gas delivery pressure (drive pressure), duty cycle (insufflation time/total cycle time), and respiratory frequency. Nine dogs, anesthetized with sodium pentobarbital, were ventilated through a cricothyrotomy cannula using a controller that allowed separate setting of drive pressure, duty cycle, and frequency. PaO2 and PaCO2 were measured after achieving steady-state gas exchange at 15 to 22 different combinations of drive pressure, duty cycle, and frequency in each dog. There were slight increases in PaCO2 and larger decreases in PaO2 as frequency was increased from 10 to 200 cycle/min. Increases in drive pressure and duty cycle resulted in reduced PaCO2 and increased PaO2. Multiple linear regression showed good correlation between PaCO2 and drive pressure, duty cycle, and frequency. The distribution of air flow between alveolar and physiologic dead space, upper airway leakage, and entrainment was determined for each set of conditions. Changes in alveolar ventilation corresponding to the blood gas changes resulted from interaction of dead-space ventilation and upper airway leakage, which varied with breath duration. Decreases in leakage during short breaths tended to compensate for the increased fractional dead-space ventilation at high frequency, thus minimizing the effects of frequency changes on gas exchange. PMID- 3086035 TI - Antiarrhythmic drug therapy of ventricular arrhythmias. PMID- 3086036 TI - Genetic control of the susceptibility to pneumococcal infection. PMID- 3086037 TI - Lps gene regulation of mucosal immunity and susceptibility to Salmonella infection in mice. PMID- 3086038 TI - Genetic approaches to the study of disease resistance: with special emphasis on the use of recombinant inbred mice. PMID- 3086039 TI - Influence of host genes on resistance of inbred mice to lethal infection with Salmonella typhimurium. PMID- 3086040 TI - Genetic control of resistance to mycobacterial infection. PMID- 3086041 TI - Genetic control of resistance to Listeria infection. PMID- 3086042 TI - Lasers in private dermatologic practice. AB - The author has collected and evaluated data from 464 cutaneous laser procedures performed on 315 patients over two and one-half years. All procedures were performed under local anesthesia in a private dermatology office. The quality of results obtained, the advantages and disadvantages of laser treatment for the treatment of cutaneous problems, comparison with more conventional therapies, and the future of the laser in dermatologic private practice are discussed. PMID- 3086043 TI - Distribution of sister chromatid exchanges in chromosomes of normal Chinese hamster and its cell lines exposed to BrdU and MMC. AB - Sister chromatid exchanges (SCEs) were investigated in chromosomes from normal male Chinese hamster (CH) and its cell lines (CHW, 1102 and 1103). The fibroblasts were grown for two replication cycles in medium containing BrdU and mitomycin C (MMC) at concentrations of 0.01, 0.02 and 0.03 micrograms/ml of medium. The difference in SCEs/cell between male CH and CHW was negligible, but the difference between CHW and 1102 was about 2.6-fold. It is suggested from karyotypic differences between CHW and 1102, that the control of SCEs might be due partly or completely to chromosome 5 in Chinese hamster. The lines CHW and 1102 were less responsive than normal Chinese hamster cells when exposed to different MMC concentrations. It is suggested that the lines CHW and 1102 might be slightly resistant to MMC. The frequency of SCEs decreased with the decrease of chromosome size. SCEs are not preferentially distributed on any autosomal chromosomes. No SCEs were found in normal X-chromosomes. The majority of exchanges appear to be either interband regions or very near band-interband junctions. PMID- 3086044 TI - Ruptured intracranial aneurysm. A clinical and pathophysiological study. PMID- 3086045 TI - A possible mechanism for mixed apnea in obstructive sleep apnea. AB - Hypopneas or pauses in respiratory effort frequently precede episodes of obstructive sleep apnea resulting in mixed apneas. We studied five subjects after chronic tracheostomy for obstructive sleep apnea. During stable non-REM (NREM) sleep, subjects breathed entirely through the tracheostomy. Tracheostomy occlusion caused experimental obstructive apnea which lasted 13.9 +/- 4.7 sec and ended with transient arousal and pharyngeal opening. At the end of the apnea there was marked hyperventilation (inspired minute ventilation rose 21.6 +/- 3.5 L on the first breath) followed by hypocapnia, hypopnea, and pauses in inspiratory effort as the subjects resumed NREM sleep. Hypocapnia was greater before inspiratory pauses lasting at least 5 sec than before shorter pauses (PETco2, 4.2 +/- 1.8 mm Hg below baseline vs 1.2 +/- 2.5 mm Hg below baseline). In three patients, pauses in inspiratory effort following experimental obstructive apnea were prevented by administration of 4 percent CO2 and 40 percent O2 inspired gas. This study suggests that: hyperventilation with hypocapnia occurs at the termination of obstructive apneas, and hypocapnia may be responsible for the attenuation or cessation of respiratory effort initiating the subsequent cycle of obstruction. PMID- 3086046 TI - Hypnosis effect on carbon dioxide chemosensitivity. AB - Hypnosis is an induced state of heightened suggestibility during which certain physiologic variables can be altered. To investigate if carbon dioxide (CO2) chemosensitivity could be blunted during this suggestible state, we measured hypercapnic ventilatory response (HCVR, delta VE/delta PaCO2), oxygen consumption (VO2), breathing pattern (VT and f), inspiratory flow rate (VT/Ti), and inspiratory timing (Ti/Ttot) in 20 healthy subjects. Mouth occlusion pressures (P0.1) were measured in the last nine subjects. Resting oxygen consumption and minute ventilation were measured during awake and hypnotic control states. The HCVR was measured spontaneously and with the suggestion to maintain normal ventilation during both awake and hypnotic conditions. It was found that without a change in metabolism, ventilatory responses to CO2 could be blunted both voluntarily, and to a greater degree, with hypnotic suggestion. These findings may have important implications in clinical settings in which patients suffer from marked dyspnea secondary to increased ventilatory chemosensitivity. PMID- 3086047 TI - Syncope in a patient with Wolff-Parkinson-White syndrome and inducible ventricular fibrillation. PMID- 3086048 TI - The susceptibility of Neisseria gonorrhoeae strains to different cephalosporins and penicillin G depends on the auxotype. AB - The relatively broad range of minimum inhibitory concentrations (MICs) of different cephalosporins and penicillin G with Neisseria gonorrhoeae results from the differing susceptibility of various subsets, i.e. auxotypes. While prototrophic and proline-dependent strains are especially resistant (p less than or equal to 0.001), AHU strains are especially susceptible. The bimodality of MIC values with penicillin G and the older cephalosporins, cephalothin and cefazoline, results from quite a big subset of relatively resistant prototrophic strains. As the newer cephalosporins from generation (e.g. cefotiam) to generation (e.g. cefmenoxime and ceftizoxime) tend to have less special problems with these strains, the general distribution of MIC values changes to monomodality. PMID- 3086049 TI - Efficacy of apalcillin alone and in combination with four aminoglycoside antibiotics against Pseudomonas aeruginosa. AB - The in vitro activity of apalcillin against 258 Pseudomonas aeruginosa strains was compared with that of 3 penicillins and 5 aminoglycosides using agar dilution tests. Apalcillin showed the highest activity of all the penicillins investigated, and of the aminoglycosides tested tobramycin and amikacin were most active. On testing the combined efficacy of apalcillin with aminoglycosides by the checkerboard technique, combinations with tobramycin or amikacin were less synergistic than combinations with gentamicin or netilmicin. Antagonistic or even only additive effects were found with none of the P. aeruginosa strains. PMID- 3086050 TI - Bactericidal activity of cefotiam and ceftizoxime against Neisseria gonorrhoeae in an in vitro model simulating plasma and cantharidal blister fluid levels after the single intramuscular application of one gram. AB - Two gonococcal strains with differing susceptibility to cefotiam and ceftizoxime, as expressed by the minimum inhibitory concentration (MIC), are exposed to continuously changing concentrations of these antibiotics as they are found in plasma and skin cantharidal blister fluid (CBF) after a single intramuscular application of 1 g. Under the conditions of the plasma level profiles, bacterial density is always greatly but not totally reduced, already during the first 1-1.5 h it declines by 99%. The effect is the more marked the quicker and higher the levels increase. In this respect, facing the less favorable CBF level profiles, a 99% reduction of gonococci takes much longer. While the degree of bacterial susceptibility plays no major role as long as the MIC is highly exceeded, as during invasion, it becomes important when the actual levels come more or less close to the MIC. Then the decline of bacterial density can slow down and even the maximum relative reduction can be affected. Under the condition of equivalent in vitro activity, the superior plasma kinetics of cefotiam leads to better antimicrobial activity, an effect no longer found facing similar CBF kinetics. This demonstrates the need for the inclusion of tissue level data, in so far as infection sites other than blood are simulated. The high degree of antigonococcal activity of the drug concentration time curves for plasma and CBF after cefotiam and ceftizoxime (1 g) allow the expected high cure rates in uncomplicated gonorrhoea. PMID- 3086051 TI - Streptococcus faecalis: in vitro susceptibility to antimicrobial drugs, single and combined, with and without defibrinated human blood. AB - Ampicillin, fusidic acid, gentamicin, imipenem, mezlocillin, ofloxacin, penicillin G, piperacillin, and vancomycin were examined for inhibitory and bactericidal activity in various broth media against 7 clinical isolates of Streptococcus faecalis. On a weight-for-weight basis, ampicillin, imipenem, mezlocillin, and ofloxacin proved to be more efficacious. All enterococcal isolates were resistant against gentamicin; fusidic acid and vancomycin lacked bactericidal activity. The combinations of either ampicillin, imipenem, mezlocillin, ofloxacin, piperacillin, or vancomycin with a subinhibitory concentration (4 micrograms/ml) of gentamicin, with or without added 65% (v/v) fresh defibrinated human blood, respectively, yielded additive effects against all enterococcal isolates. The addition of fresh human blood failed to enhance the antienterococcal activity of 4 micrograms/ml of gentamicin; in contrast, addition of 65% (v/v) fresh or heat-inactivated (56 degrees C, 30 min) normal rabbit, bovine, and human sera augmented the activity of gentamicin, an effect that was ablated through the addition of either 0.005 M DTT or 0.01 M MgCl2 + 0.01 M EGTA + 0.01 M CaCl2, supplements known to antagonize human serum beta lysin, but not lysozyme activity. PMID- 3086052 TI - [Radiotherapy of bone tumors]. PMID- 3086053 TI - [Endoscopic percutaneous gastrostomy--a comparison of methods]. PMID- 3086055 TI - Treatment of retrocaval ureter. AB - Retrocaval ureter is a developmental anomaly of the course of the ureter in relation to the inferior vena cava. In spite of the fact the pathophysiological consequences of this anomaly are very serious, clinical manifestations are relatively poor. Experience with the management of this disorder in our 4 patients justifies the therapy we applied. It involves resection of a part of the ureter running behind the inferior vena cava, transposition of the ureter and subsequent end-to-end anastomosis of both parts of the ureter or of the ureter directly with the pelvis. The results verified at postoperative check-up examinations were very good, demonstrating the correctness of the tactics and procedure used. PMID- 3086056 TI - Modern approaches to the treatment of male urethral strictures. AB - Therapeutic results in 172 male patients treated for urethral strictures are analysed. The strictures were observed after Johanson's reconstruction (19.4%), Blandy's urethroplasty (15.2%) and optical urethrotomy (15.9%), respectively. In optical urethrotomy and the two-stage urethroplasties about the same percentage of strictures was seen. Since optical urethrotomy is a simple operation, it is indicated primarily in the majority of patients. However, it cannot cure all strictures, thus it is necessary to master also the other therapeutic procedures, of which some are also indicated as a primary therapy. The authors present their own indications for the individual therapeutic procedures. PMID- 3086054 TI - Long-term results of treatment of urethral strictures by transpubic urethroplasty. AB - Intrapelvic ruptures of membraneous urethra connected with pelvis fractures lead, as a rule, to strictures. Relative inaccessibility of these strictures above diaphragma urogenitale and behind symphysis makes their surgical treatment difficult. Transpubic approach with removal of wedge of pubic bones enables a direct approach to stricture and its modification under sight control. Technique of transpubic approach is described and long-term results obtained in 10 patients being 29-54 months after operation are evaluated. In one patient urinary continence in a sense of stress incontinence was disturbed, in one patient impotence occurred and one patient had disturbed gait. PMID- 3086057 TI - Diagnostic and therapeutic problems of acute scrotum. AB - In retrospective study of 90 patients operated on for acute unilateral pains in scrotum region and its content--the so-called acute scrotum--during revision torsion of testis was found 48 times (53.3%), torsion of appendix testis 24 times (26.7%), acute epididymitis 17 times (18.9%) and testis tumour in one patient (1.1%). Comparing clinical symptoms, local finding in scrotum and laboratory findings among individual groups of patients a finding which could clearly distinguish torsion from acute epididymitis was not found. If torsion of testis cannot be reliably excluded, immediate revision of scrotum content must be carried out. PMID- 3086058 TI - Construction of fistula between a. brachialis and v. basilica transposed into subcutaneous tissue of the arm as a preparation for haemodialysis treatment. AB - Technique and tactics of the construction of arteriovenous fistula between a. brachialis and v. basilica transposed into the subcutaneous tissue of the arm are described. It is advantagenous to use this fistula construction in "problematic" patients when there are no other possibilities for an arteriovenous shunt. In comparison with arteriovenous fistulas of vascular grafts and of artificial vascular prostheses the described method has an advantage only in one vascular anastomosis, since straight fistula form is involved, kinking of the arterialized vein cannot occur and, finally, fistula is formed from an autologous vessel which is always thick enough even in little children and gracile women. PMID- 3086059 TI - A, B, O blood groups and the course of breast cancer disease. AB - 551 clinical records of breast cancer patients were retrospectively analysed. Several parameters have been examined: age at presentation, distribution of stages at the time of diagnosis, incidence of any progression and "progression- free" interval after primary treatment, incidence of distant dissemination and distant meta- free interval, cancer mortality, time of survival from presentation and time of survival from detection of distant metastases (stage at presentation being taken into account in all evaluations). The results within various ABO blood groups were mutually compared. There were no substantial differences in these parameters within different blood groups. Immunological point of view, dealing with possible loss or modifications of ABH (O) isoantigens on tumour cells and the immune response to these alien antigens, is discussed. PMID- 3086060 TI - Comparative study of percentage of T-lymphocytes in blood in patients with breast and thyroid cancer. AB - The authors have studied the percentage of T-lymphocytes detected by means of an acid non-specific esterase technique (ANAE) in venous blood in patients with malignant tumors of mammary and thyroid glands. The examination was concentrated especially on a group of patients with both metastatic and non-metastatic tumors. The examination was performed before and after operation. It was found the the percentage of T-lymphocytes had been significantly higher in non-metastasizing tumors than in healthy individuals and lower both in metastasizing tumors and healthy controls. The percentage of T-lymphocytes in tumor-patients is relatively higher prior to operation than after it. Although the interpretation of these results is not easy, however, one may presume, that behavior of T-lymphocytes is a signal for alterations in immune system of the patients; further and more specific investigation is therefore urgent. This method is very useful in practice for monitoring mammary gland and thyroid tumors and perhaps other malignancies. PMID- 3086061 TI - Effect of single and repeated doses of oral omeprazole on gastric acid and pepsin secretion and fasting serum gastrin and serum pepsinogen I levels. AB - The effect of omeprazole on gastric acid and pepsin secretion and fasting serum gastrin and serum pepsinogen I levels was studied in 12 healthy volunteers. Omeprazole, 40 mg enteric-coated granules, or placebo was given once daily for nine days in a double-blind crossover study design. Twenty-four hours after a single dose of omeprazole, mean basal and mean pentagastrin-stimulated acid output decreased significantly. This effect was more pronounced after nine days of treatment. Basal pepsin output was significantly reduced only in those subjects with basal anacidity during omeprazole treatment. Stimulated pepsin output was slightly reduced after a single dose but unaltered after nine days of omeprazole. Fasting serum gastrin and serum pepsinogen I levels increased significantly during omeprazole treatment. It is concluded that omeprazole is a potent and selective inhibitor of gastric acid secretion, probably without a direct effect on pepsin secretion. However, in cases of basal anacidity during omeprazole administration, basal pepsin secretion is reduced. During omeprazole treatment, fasting serum levels of gastrin and pepsinogen I rise. PMID- 3086062 TI - Nasoenteric feeding tubes. Radiographic detection of complications. AB - Recent technical refinement of feeding tubes and formula infusion pumps has led to widespread clinical use of long-term nasoenteric alimentation. We evaluated 340 hospitalized adults after placement of flexible, small-bore feeding tubes. These debilitated or critically ill patients were intubated transnasally at their bedside without fluoroscopic guidance, but portable radiographs of the chest and abdomen were obtained routinely for tube localization before administering liquid nutrients. Various complications were detected in 26 cases (7.6%). Tube malposition into the airways (seven patients) or within the pharynx and esophagus (eight patients) was the most common problem; it occurred in 4.4% of all cases. Radiographic findings in 11 other patients included tube-induced perforation of the lung (one case), massive aspiration (three), malfunction of knotted tubes (three), and rupture of their mercury capsule within the gastrointestinal tract (four). Our observations indicate a need for careful radiographic localization of the feeding tubes at the time of insertion and their periodic monitoring throughout the course of nasoenteric alimentation. PMID- 3086063 TI - Chromium deficiency after long-term total parenteral nutrition. AB - A 63-year-old female developed unexplained hyperglycemia and glycosuria during administration of a total parenteral nutrition regimen on which she had been stable for several months. Because the patient had no history of diabetes or evidence of an infection, chromium deficiency was considered. Plasma chromium level was 0.1 microgram/dl (laboratory reference interval: 1.8-3.8 micrograms/dl). Fourteen days of supplemental intravenous chromium chloride (200 micrograms/day) allowed complete withdrawal of exogenous insulin with no further hyperglycemia or glycosuria. Correction of unexplained glucose intolerance following vigorous chromium supplementation indicates that the patient had chromium deficiency. Subsequent plasma chromium levels remained unchanged, possibly reflecting the sensitivity limits of the assay that was used, the uncertainty that exists regarding appropriate reference intervals for this element, and the fact that plasma levels do not always correlate with total body stores. The patient did not manifest peripheral neuropathy, which was present in one of the two previously reported cases, nor encephalopathy, which was reported in the other. We conclude that this patient developed chromium deficiency as a result of inadequate administration of chromium in the parenteral formula (6 micrograms/day) plus excessive enteric losses, and she presented with glucose intolerance as the only clinical manifestation of the deficiency. Caution should be exercised when interpreting plasma chromium in patients with suspected deficiency. PMID- 3086064 TI - Effects of age and sex on the hepatic monoxygenase system: a correlative approach. AB - The following studies compare developmental patterns of a hepatic monoxygenase system using (1) the aminopyrine (Ap) breath test, (2) in vivo Ap pharmacokinetics (clearances) and (3) in vitro Ap demethylation by hepatic microsomes. Together, the three methodological approaches indicate that hepatic metabolism of Ap increases from the fetal stage through 70 days of age with the male showing a significantly greater drug metabolizing capacity than the female. However, sex and developmental patterns derived by the three methodologies do not necessarily correlate quantitatively, due to a number of complex variables (i.e., liver size, drug volume of distribution, etc.) less likely encountered in the adult of fixed age and mature sexual development. PMID- 3086065 TI - Alfentanil in anesthesia and analgesia. AB - Alfentanil is a tetrazole derivative of fentanyl. Many of the pharmacologic effects of alfentanil are similar to those of fentanyl and sufentanil, but of quicker onset than those of fentanyl and of shorter duration than those of fentanyl and sufentanil. Alfentanil may cause less intense respiratory depression than equianalgesic doses of fentanyl. Alfentanil has a lower total body clearance, smaller volume of distribution, and shorter half-life than fentanyl and sufentanil. Clinical trials indicate alfentanil can be used effectively as an analgesic, an analgesic supplement to anesthesia, an anesthetic induction agent, and as the major component of a general anesthetic. Its short duration of effect makes it attractive as an analgesic supplement for short ambulatory surgical procedures. Alfentanil is recommended for addition to drug formularies, but its use should be restricted to anesthesia personnel. PMID- 3086066 TI - Transdermal glyceryl trinitrate patches (Transiderm-Nitro). PMID- 3086067 TI - [Proven relationship between drugs and pancreatitis]. PMID- 3086069 TI - Biliary sepsis. Reviewing treatment options. AB - Bactobilia is a frequent accompaniment of obstruction in the biliary tract, organisms present being normal intestinal aerobes and anaerobes. Bacterial colonisation of the bile may occur asymptomatically, may predispose to infection postoperatively, or may be associated with an attack of acute cholecystitis, occurring secondary to obstruction. The choice of an antimicrobial regimen for biliary infection should take into account the expected antibiotic sensitivities of organisms colonising bile, whether biliary obstruction or bacteraemia is present, and the activity of the antibiotic in bile. Often, high biliary concentrations of an antibiotic cannot be achieved due to obstruction, and in many cases high blood and tissue concentrations are of greater importance. Surgical prophylaxis should be reserved for patients at high risk of bactobilia (e.g. the elderly), when obstruction is present, for immunosuppressed patients, and those with artificial heart valves. A single perioperative dose of a 'first' or 'second generation' cephalosporin, gentamicin, or co-trimoxazole is effective. Antibiotic therapy for acute cholecystitis should be instituted if there is evidence of systemic toxicity, when surgery is to be delayed, or in patients with identified risk factors for bactobilia. Ampicillin or a cephalosporin may be appropriate in less severe disease, while in seriously ill patients, an aminoglycoside or cephalosporin with metronidazole or clindamycin is appropriate. Oral regimens include amoxycillin, an oral cephalosporin, or co-trimoxazole, in combination with metronidazole. In acute cholangitis, systemic therapy similar to that recommended for acute cholecystitis is indicated. Patients with recurrent cholangitis may have relatively antibiotic-resistant bacteria and efforts should be made to obtain a bacteriological diagnosis. Long term suppressant therapy with oral agents such as amoxycillin, cephalexin, or co-trimoxazole may be tried. PMID- 3086068 TI - [Primary polyuric kidney failure and acute yellow liver dystrophy following infusion of glucose substitutes in children]. AB - Four children (aged 2 1/2-14 years) were given infusions of fructose, sorbitol and xylitol after sustaining head trauma (n = 3) or after attempted suicide with carbromal (n = 1). After transitory polyuria renal failure of varying severity set in three to five days after onset of the infusion treatment. Serum osmolality fell to 265-274 mosm/kg, haematocrit to 0.25-0.31, and hyponatraemia developed. Serum creatinine rose to maximally 256-930 mumol/l. Liver damage developed in parallel to the renal failure, two children dying with acute yellow liver atrophy. Two children--given symptomatic treatment with balanced equalization of the hyponatraemia, administration of frusemide and adjusted carbohydrate substitution--were discharged after four to eight weeks with normal renal and hepatic functions. Dialysis was not required. The hepatic and renal abnormalities must have been due to the high amounts of fructose, sorbitol and xylitol, to a total of 7.1-23.0 g/kg on the first day, well above recommended levels. PMID- 3086070 TI - Neonatal ventilation. PMID- 3086071 TI - Longitudinal distribution of brush border hydrolases and morphological maturation in the intestine of the preterm infant. AB - The morphological maturation and the distribution of brush border hydrolase activities were studied in the small intestine and the colon in newborn babies of 28-38 weeks gestational age. Lactase and sucrase activities were higher at term with maximal activity in the proximal intestine. In contrast, aminopeptidase and glucoamylase exhibited maximum activity in the distal part of the small bowel. Glucoamylase activity was already significant in the small intestine and in the colon of the preterm newborn. Sucrase activity present in the proximal colon of the preterm dropped to a negligible amount at term, whereas aminopeptidase activity increased, reaching values found in the small intestine. The enzymic changes occurring in the intestinal tract were related to the morphological maturation of the mucosa from fetal to adult type during late gestation. Accelerated morphological and functional maturation was observed in one preterm infant nourished intravenously for 12 days, these processes being independent of the presence of nutrients in the intestine. At term, the distal part of the intestine seems to have increased digestive capacities for peptides and polysaccharides. We present evidence that full-term, and to a lesser extent preterm infants are able to hydrolyse glucose polymers. PMID- 3086072 TI - Lasers for use in medicine. AB - During the last quarter century the use of directed energy from lasers has become very important in medicine. Directed energy from lasers has been used to cut tissue, to cauterize bleeding, to drill small pressure relief holes and to selectively destroy tissue growths. In this paper lasers of interest in such applications are described and compared. PMID- 3086073 TI - Urine recovery experiments with quercetin and other mutagens using the Ames test. AB - Recovery from urine of the mutagenic activity of 2-anthramine, cyclophosphamide, 7,12-dimethylbenz[a]anthracene, 6-chloro-9-((3-(2-chloroethylamino)-propyl)amino) 2-methoxyacridin e dihydrochloride (ICR-191), mitomycin-C, nitrofurantoin, and quercetin was studied with several of the Ames tester strains using acetone extracted XAD-2 columns with yields ranging from 27% to 79%. Dose responses of the pure chemicals were also studied, and results showed TA 97 to be far more susceptible to quercetin mutagenesis than TA 1537. Reducing pour plate agar volume enhanced mutagenesis. PMID- 3086074 TI - Comparison of S9 mix and hepatocytes as external metabolizing systems in mammalian cell cultures: cytogenetic effects of 7,12-dimethylbenzanthracene and aflatoxin B1. AB - Two external metabolizing systems, S9 mix from Aroclor-induced rat livers and freshly isolated hepatocytes, were used for activation in cultures of human lymphocytes and V79 cells. 7, 12-dimethylbenzanthracene (DMBA) and aflatoxin B1 (AFB1) were employed as indirectly acting reference mutagens. Mutagenic effects were measured by induction of sister chromatid exchange (SCE). With DMBA, SCE inducing effects were found to be quite similar after activation by S9 mix and activation by hepatocytes. In human lymphocytes nearly the same dose-effect relationships were found with both metabolizing systems; in V79 cells the hepatocyte-mediated induction of SCE was detectable at slightly lower concentrations than the S9-mediated SCE induction. In contrast with AFB1, S9 activation led to a stronger SCE induction than hepatocyte activation in both target cells. The induction of chromosomal aberrations by AFB1 after activation by the two metabolizing systems was also analysed in V79 cells. This experiment again revealed that AFB1 was more efficiently activated by S9 mix than by hepatocytes, and it appeared that AFB1 is a more potent inducer of chromosomal aberrations than of SCE. The different activation capacities of the two metabolizing systems for AFB1 may be due to the maintenance of inactivation mechanisms in hepatocytes or to the Aroclor induction of the S9 fraction. Our experiments have shown that the suitability of hepatocytes as an activation system is not restricted to microbial or eukaryotic point mutation assays, but that hepatocyte metabolism can also be successfully included in cytogenetic tests with short- and long-term cultures of mammalian target cells. PMID- 3086076 TI - NMR studies of crab and plaice metallothioneins. AB - Metallothioneins isolated from the hepatopancreas of the edible crab (Cancer paqurus) and the plaice (Pleuronectes platessa) after cadmium injection are predominantly cadmium proteins containing only small amounts of zinc and traces of copper. The removal of metal ions from the two metallothioneins by EDTA was studied using proton NMR spectroscopy. The rates of removal of cadmium and zinc were monitored directly from the intensity of the resonances due to the cadmium and zinc-EDTA complexes. Nearly all the zinc present in the protein was extracted by EDTA relatively rapidly, whereas only 10 to 20% of the total cadmium was removed in at least three steps. The total (Cd + Zn) metal removed at equilibrium was 1.2 to 1.8 g-ions/mole protein. Information on conformational changes in the protein were also obtained from studying alterations in the proton resonances of the protein. This was directly correlated with removal of metal from the protein. The coordination environments of the cadmium ions in crab metallothionein were investigated by using 113Cd-NMR, and compared with 113Cd-NMR spectra of rabbit liver MT-II and Scylla serrata MT-I. PMID- 3086075 TI - Effects of heavy metals on Drosophila larvae and a metallothionein cDNA. AB - Drosophila melanogaster larvae reared on food containing radioactive cadmium retained over 80% of it, mostly in the intestinal epithelium. The majority of this radioactivity was associated with a soluble protein of less than 10,000 molecular weight. Synthesis of this cadmium-binding protein was induced by the metal as demonstrated by incorporation of radioactive cysteine. Most copper ingested by larvae was also found to associate with a low molecular weight, inducible protein, but some of it was found in an insoluble fraction. Zinc was unable to, or very inefficient at, binding or inducing the synthesis of a similar protein. A D. melanogaster cDNA clone was isolated based on its more intense hybridization to copies of RNA sequences from copper-fed larvae than from control larvae. This clone showed strong hybridization to mouse metallothionein-I cDNA at reduced stringency. Its nucleotide sequence includes an open-reading segment which codes for a 40-amino acid protein; this protein was identified as metallothionein based on its similarity to the amino-terminal portion of mammalian and crab metalloproteins. The ten cysteine residues present occur in five pairs of near-vicinal cysteines (Cys-X-Cys). This cDNA sequence hybridized to a 400-nucleotide polyadenylated RNA whose presence in the cells of the alimentary canal of larvae was stimulated by ingestion of cadmium or copper; in other tissues this RNA was present at much lower levels. Mercury, silver, and zinc induced metallothionein to a lesser extent. Whether (any of) the protein(s) discussed above correspond(s) to that coded by this RNA sequence has not yet been determined. PMID- 3086077 TI - Absorption, metabolism, and excretion of di(2-ethylhexyl) phthalate by rats and mice. AB - There is convincing evidence in the literature that most of the adverse biological effects of phthalate diesters are actually effects of metabolites rather than of the parent compounds. If so, the dramatic species differences in endpoint metabolic profiles make it essential that metabolism of phthalates be understood in detail, including the factors that may alter the metabolism. A metabolic pathway for phthalates having saturated alkyl groups has been postulated based on identification of metabolites produced in vivo and excreted in urine. The first few steps in the postulated pathway have been confirmed in vitro using enzymatically active preparations from rats and mice; some details of the nature of these early steps have been learned. Although some information concerning later steps is available, much remains to be learned in this area. Species differences are postulated to involve kinetics of several biochemical and physiological events acting in concert or competition. Among these interacting factors are competition of at least three enzymes for phthalate monoesters as substrate, relative kidney clearance rates for different metabolites, relative Km values of oxidative enzymes for the same precursors in different species, and relative equilibria between glucuronide formation and hydrolysis. Essential information that must be obtained in the future includes which metabolites play a causal role in which biological effects, and what factors (age, diet, state of health, etc.) can modify the metabolism of phthalate esters and in what way. PMID- 3086078 TI - Comparative pharmacokinetics and subacute toxicity of di(2-ethylhexyl) phthalate (DEHP) in rats and marmosets: extrapolation of effects in rodents to man. AB - Certain phthalate esters and hypolipidemic agents are known to induce morphological and biochemical changes in the liver of rodents, which have been associated with an increased incidence of hepatocellular tumors in these species. There is evidence that hypolipidemic agents do not induce these effects in either subhuman primates or man. The oral and intraperitoneal administration of di(2 ethylhexyl) phthalate (DEHP) to the marmoset monkey at doses up to 5 mmole DEHP/kg body weight/day for 14 days did not induce morphological or biochemical changes in the liver or testis comparable with those obtained in rats given the same amount of DEHP. In the marmoset, the excretion profile of [14C]-DEHP following oral, IP, and IV administration and the lower tissue levels of radioactivity demonstrated a considerably reduced absorption in this species compared to the rat. The urinary metabolite pattern in the marmoset was in many respects qualitatively similar to but quantitatively different from that in the rat; the marmoset excreted principally conjugated metabolites derived from omega- 1 oxidation. The pharmacokinetic differences between these two species indicate that the tissues of the marmoset are exposed to a level of DEHP metabolites equivalent to the complete absorption of a dose of Ca. 0.1 to 0.25 mmole DEHP/kg body weight/day without significant toxicological effects. These exposure levels are at least 100-fold greater than the worst estimates of incidental human exposure (ca. 0.0015 mmole/kg/day). They are comparable with the human therapeutic dose of many hypolipidemic drugs (ca. 0.15 mmole/kg/day), a dose at which it is claimed that there is an absence of morphological or biochemical changes to human or subhuman primate liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086079 TI - Physiological and chemical characterization of cyanobacterial metallothioneins. AB - Techniques have been developed for detection, quantitation, and isolation of bacterial metallothioneins (MTs) from cyanobacterial species. These methods involve differential pulse polarography and reverse-phase high-performance liquid chromatography (HPLC) and have allowed detection of picomole quantities of these high sulfhydryl content proteins. The prokaryotic molecule was found to be induced in the presence of Cd or Zn salts with regulation at the level of transcription. Cu was not found to induce synthesis of the prokaryotic MT. Exposure to the former metals resulted in a growth lag followed by simultaneous induction of MT synthesis and onset of growth. Amino acid analysis and N-terminal sequence analysis indicated that the bacterial MTs from cyanobacteria are unique, having many aromatic and aliphatic residues and no apparent association of hydroxylated or basic amino acids with cysteines. Although the characteristic Cys X-Cys sequences were present, no apparent amino acid sequence homology with the eukaryotic MTs was found in the first 42 residues. PMID- 3086081 TI - Spontaneous and induced sister chromatid exchanges in lymphocytes of healthy persons. AB - Spontaneous and mitomycin C-induced sister chromatid exchanges (SCEs) in lymphocytes were analyzed in 46 healthy persons. Our results suggest that the frequency of spontaneous SCE in lymphocytes is useful for evaluation of the biological effects of environmental mutagens, and that the induced-SCE test with a mutagen and lymphocytes may be used to detect persons with a high sensitivity to the mutagen. PMID- 3086080 TI - In vitro release of arachidonic acid and in vivo responses to respirable fractions of cotton dust. AB - It was considered that the fall in lung function seen after exposure to cotton dust may be attributable in part to the activity of arachidonic acid metabolites, such as leucotrienes as well as to the more established release of histamine by cotton dust. However, we found that cotton and barley dusts elicited poor release of arachidonic acid from an established macrophage like cell line compared with that observed with other organic dusts. In the experimental animal, pulmonary cellular responses to both cotton and barley dust were similar to those evoked by moldy hay and pigeon dropping dusts, although after multiple doses a more severe response was seen to cotton and barley. Since both moldy hay and pigeon droppings elicit a greater arachidonic acid release than cotton or barley, a role for arachidonic acid in inducing the cellular response is less likely than other factors. There are limitations to our conclusions using this system, i.e., the arachidonic acid may be released in a nonmetabolized form, although it is noted that the two dusts with the greatest arachidonic acid release produce their clinical responses in humans largely by hypersensitivity mechanisms. PMID- 3086083 TI - Biophysical characterization of osteoporotic bone. AB - A number of biophysical and biochemical parameters have been measured in normal and osteoporotic animals and their bones. Rats have been fed normal and calcium- and phosphorus-deficient diets (through mineral content) from the weaning period to maturity (greater than 125 days). The experiments were performed after attaining this age. Biochemical parameters considered for comparison included: red blood cells (RBC), white blood cells (WBC), Hb, serum calcium and phosphorus, blood pH, PCO2, and PO2. Bones obtained after sacrificing mature animals were used for obtaining data regarding infrared, fluorescence, and X-ray spectra, and transmission electron micrographs, and were also subjected to spectrochemical analysis. It was found that the two sets of results show differences in most of the above-mentioned parameters, which correlates well with the loss of calcium and phosphorus metabolism and the corresponding increase in the amorphous-to crystalline ratio. It is hoped that these data will be useful in characterizing the osteoporotic bone and will suggest the mechanism for reversal by external stimulations. PMID- 3086082 TI - Thyroid-vitamin A interactions in chicks exposed to 3,4,3',4' tetrachlorobiphenyl: influence of low dietary vitamin A and iodine. AB - Poultry chicks receiving a low vitamin A semipurified diet and exposed to 3,4,3',4'-tetrachlorobiphenyl became hypothyroid in comparison with unexposed controls. Metabolic rate, total serum thyroxine, total serum triiodothyronine, and food intake decreased significantly while thyroid weight increased. Unexpectedly, growth rate was not affected on this diet. In the case of chicks receiving a low vitamin A--low iodine semipurified diet and exposed to the PCB congener, the hypothyroid response was apparently antagonized. Comparing exposed chicks with unexposed controls, metabolic rate and the proportion of free T3 (i.e., %T3 resin uptake) increased while total serum thyroxine and thyroid weight were unchanged. In addition, growth rate, food consumption, and serum retinol decreased on this diet. These results are interpreted to mean that growth rate may have been altered by circulating levels of retinol, and vitamin A insufficiency may predispose birds to the hypothyroid effects of PCBs. PMID- 3086084 TI - Evidence that expression of c-fos protein in amnion cells is regulated by external signals. AB - While c-fos expression is normally very low in certain cell types but transiently inducible by growth factors (e.g. in fibroblasts), other cells (e.g. amnion cells) exhibit an apparently constitutive expression in vivo. Here we show that in primary amnion cells c-fos protein expression rapidly drops to undetectable levels following plating in normal growth medium. However, c-fos expression is inducible by, and maintained at high levels in the presence of, dialyzed placenta or embryo-conditioned medium. These observations suggest that c-fos expression in primary amnion cells is regulated by placenta- and embryo-derived factor(s), providing further evidence for the hypothesis that transcription of the c-fos gene may generally be controlled by external signals. We also show that proliferation of primary amnion cells is not dependent on a high c-fos expression, suggesting that the function of c-fos is more likely to be associated with other cellular functions in the differentiated amnion cell. PMID- 3086085 TI - Interleukin-3-dependent expression of the c-myc and c-fos proto-oncogenes in hemopoietic cell lines. AB - Using Northern blot analysis the expression of several proto-oncogenes was studied in established lines of mast cell precursors. Upon removal of interleukin 3 (IL-3) from the culture medium, factor-dependent cells stop dividing. During the first 7 h, however, normal amounts of total cellular mRNAs are maintained, and this is reflected in unchanged levels of several transcripts, such as actin, c-Ha-ras and c-fes. In contrast, within 1.5 h of IL-3 removal, the levels of c myc and c-fos mRNAs decrease drastically and addition of IL-3 at that stage quickly induces back the levels found in actively growing cultures. In factor independent cells, which proliferate actively even in the absence of IL-3, high levels of c-myc and c-fos transcripts are maintained in the absence of growth factor. In cells arrested by serum starvation, addition of 10% serum induces massive amounts of c-fos transcripts, but not of c-myc, and cell proliferation is not restored. The data suggest that the c-myc and c-fos proto-oncogenes play an important role in mediating the multiple effects of IL-3 on hemopoietic progenitor cells. PMID- 3086086 TI - Molecular characterization of synaptophysin, a major calcium-binding protein of the synaptic vesicle membrane. AB - Synaptophysin, a mol. wt 38 000 glycopolypeptide of the synaptic vesicle membrane, was solubilized using Triton X-100 and purified by immunoaffinity or ion-exchange chromatography. From gel permeation and sucrose-density centrifugation in H2O/D2O, a Stokes radius of 7.3 nm, a partial specific volume of 0.830 and a total mol. wt of 119 000 were calculated for the native protein. Cross-linking of synaptic vesicles with glutaraldehyde, dimethylsuberimidate, or Cu2+ -o-phenantroline, resulted in the formation of a mol. wt 76 kd dimer of synaptophysin. Crosslinking of the purified protein in addition produced tri- and tetrameric adducts of the polypeptide. Native synaptophysin thus is a homooligomeric protein. Synaptophysin is N-glycosylated, since cultivation of the rat phaeochromocytoma cell line PC12 in the presence of tunicamycin reduced its mol. wt by about 6 kd. Upon transfer to nitrocellulose and incubation with 45Ca2+, synaptophysin behaved as one of the major calcium-binding proteins of the synaptic vesicle membrane. Pronase treatment of intact synaptic vesicles abolished this 45Ca2+ binding indicating that the Ca2+ binding site of synaptophysin must reside on a cytoplasmic domain of the transmembrane polypeptide. Based on these data, we propose that synaptophysin may play an important role in Ca2+-dependent neurotransmitter release. PMID- 3086087 TI - Appropriate glycosylation of the fms gene product is a prerequisite for its transforming potency. AB - Processing inhibitors of N-linked glycans were used to determine whether correct glycosylation of the oncogene product gp140v-fms, encoded by the McDonough strain of feline sarcoma virus (SM-FeSV), is required to maintain the oncogenic properties of v-fms. SM-FeSV-transformed cells treated with the glucosidase-I inhibitors N-methyldeoxynojirimycin (MdN) or castanospermine synthesized predominantly a gp125v-fms species which had a normal half life. The molecule was transported to the plasma membrane and exhibited normal kinase activity as determined by autophosphorylation. However, although no significant change in cell morphology of the SM-FeSV-transformed cells was observed in the presence of castanospermine, growth of these cells became strictly serum-dependent. In addition, growth in soft agar was drastically retarded despite the presence of 10% calf serum, indicating that the transformed properties of the cells were altered. In contrast, swainsonine, an inhibitor of the processing alpha mannosidase-II, had no effect. Cells transformed by the Snyder Theilen strain of FeSV were used to demonstrate that the altered proliferative properties were directly linked to the modified structure of the fms gene product. Our data suggest that the extracellular domain of gp140v-fms plays a role in regulating cell proliferation. PMID- 3086090 TI - Somatic antigens of Pseudomonas aeruginosa. The structure of O-specific polysaccharide chains of P. aeruginosa O10 (Lanyi) lipopolysaccharides. AB - Mild acid degradation of lipopolysaccharides from Pseudomonas aeruginosa O10a and O10a,b (Lanyi classification) resulted in O-specific polysaccharides built up of trisaccharide repeating units containing 2-acetamido-2,6-dideoxy-D-glucose (N acetylquinovosamine, DQuiNAc), 2-acetamido-2,6-dideoxy-D-galactose (N acetylfucosamine, DFucNAc), and 5-acetamido-3,5,7,9-tetradeoxy-7-[(R)-3 hydroxybutyramido] -L-glycero-L-manno-nonulosonic acid. The latter is a di-N-acyl derivative of a new sialic-acid-like sugar which was called by us pseudaminic acid (PseN2). A 3-hydroxybutyric acid residue was also found in natural carbohydrates for the first time. In the O10a,b polysaccharide pseudaminic acid carried an O-acetyl group at position 4. For selective cleavage of the O10a polysaccharide, solvolysis with hydrogen fluoride was employed which, owing to the relatively high stability of the glycosidic linkage of pseudaminic acid, led to the disaccharide with this sugar on the non-reducing terminus. Performing the solvolysis in methanol afforded the methyl glycoside of this disaccharide which proved to be more advantageous for further analysis. Carboxyl-reduction made the glycosidic linkage of pseudaminic acid extremely labile, and mild acid hydrolysis of the carboxyl-reduced 010a polysaccharide afforded the trisaccharide with a ketose derivative on the reducing terminus. Establishing the structure of the oligosaccharide fragments obtained and interpreting the 13C nuclear resonance spectra of the polysaccharides allowed to determine the following structure for their repeating units: (formula: see text) In the polysaccharides the N acetylquinovosamine residue is attached not to pseudaminic acid itself, but to its N-acyl substituent, 3-hydroxybutyryl group, and thus the monomers are linked via both glycosidic and amidic linkages. PMID- 3086088 TI - Spatial and temporal pattern of hsp26 expression during normal development. AB - The tissue-specific patterns of developmental expression of hsp26-lacZ fusion genes inserted into Drosophila melanogaster by germline transformation were analyzed in several transformant lines utilizing a histochemical assay for beta galactosidase activity on whole animals. We compared this pattern to the tissue specific distribution of endogenous hsp26 RNA determined using hybridization of probes to RNA in situ in tissue sections. Both assays reveal that hsp26 is expressed in numerous tissues during development including spermatocytes, nurse cells, epithelium, imaginal discs, proventriculus and neurocytes. The ease and resolution of the whole-animal beta-galactosidase assay makes it particularly attractive for the elucidation of sequences involved in such complex regulation. The original hsp26-lacZ fusion gene contained 2 kb of sequence upstream of the transcription start. A construct containing only 278 bp upstream was still expressed in spermatocytes but no longer in nurse cells. In a few instances, the fusion genes were expressed in tissues for which there was no evidence for expression of the endogenous hsp26 gene. These novel patterns appear to be a result of chromosomal position since they were observed in only one or a subset of transformant lines containing identical inserts. PMID- 3086089 TI - Mechanism of the phosphorylase reaction. Utilization of D-gluco-hept-1-enitol in the absence of primer. AB - alpha-Glucan phosphorylases from rabbit skeletal muscle, potato tubers and Escherichia coli catalyze the utilization of 2,6-anhydro-1-deoxy-D-gluco-hept-1 enitol (heptenitol) in the presence of arsenate or phosphate. 1H-NMR analysis in the presence of 2H2O and arsenate indicated formation of 1-[1-2H]deoxy-alpha-D glucoheptulose with rates comparable to the arsenolysis of poly- or oligosaccharides. The reaction depends on the presence of a dianionic 5' phosphate group of pyridoxal in the active conformation of the phosphorylases. Heptenitol is the first known substrate of alpha-glucan phosphorylases which does not require a primer. This is explained by the finding that heptenitol is exclusively used as substrate for the degradative pathway of the phosphorylase reaction where it competes with polysaccharide substrates. In the presence of phosphate the reaction product is 1-deoxy-alpha-D-gluco-heptulose 2-phosphate (heptulose-2-P), which subsequently inhibits the reaction. This characterizes heptulose-2-P as an enzyme-derived inhibitor. The Ki = 1.9 X 10(-6) M with potato phosphorylase suggests the formation of a transition-state-like enzyme-ligand complex. These findings, together with the fact that the phosphates of heptulose 2-P and pyridoxal 5'-phosphate are linked by hydrogen bridges [Klein, H. W., Im, M. J., Palm, D. & Helmreich, E. J. M. (1984) Biochemistry 23, 5853-5861], make it likely that both phosphates are involved in phosphorylase catalysis. A catalytic mechanism of phosphorylase action is proposed in which a 'mobile' phosphate anion plays a versatile role. It serves as proton carrier for the substrate activation, it stabilizes the intermediate and acts as a nucleophile which can accept a glycosyl residue reversibly. PMID- 3086091 TI - A small diffusion pore in the outer membrane of Pseudomonas aeruginosa. AB - The permeability properties of the outer membrane of Pseudomonas aeruginosa were re-examined, since the reported conclusions are conflicting [Decad, M. G. and Nikaido, H. (1976) J. Bacteriol. 128, 325-336; Caulcott, C. A., Brown, M. R. W. and Gonda, I. (1984) FEMS Microbiol. Lett. 21, 119-123]. On the basis of the experimental evidence to be described below we conclude that the exclusion limit of the outer membrane of P. aeruginosa is smaller than the size of uncharged disaccharides but larger than the size of hexose. This conclusion is based on the following evidence. Penetration of monosaccharides into the expanded periplasm was large and that of disaccharides was small, after the cells were plasmolyzed with 600 mosM NaCl. A significant amount of protein was released after osmotic down-shock of cells treated with the hypertonic monosaccharides but not of cells treated with the hypertonic saccharides larger than disaccharides. Centrifuged pellets of cells treated with hypertonic di, tri and tetrasaccharides weighed about 15-20% less than that of cells treated with the isotonic monosaccharide, suggesting that the osmotic pressure was exerted on the outer membrane causing dehydration and shrinking of the cells. By contrast, cells treated with the hypertonic pentose and hexoses weighed about 0.1% and 6% less, respectively, than cells treated with the isotonic saccharide, suggesting that pentose diffused through the outer membrane freely. PMID- 3086092 TI - Is there Ca2+(Sr2+)-3-hydroxybutyrate symport in rat-liver mitochondria? A reappraisal. AB - The observation in this laboratory that respiration and Sr2+ import were stimulated by the addition of 3-hydroxybutyrate to suspensions of N ethylmaleimide-treated mitochondria respiring in state 6, after the addition of Sr2+, in a sucrose medium containing choline as substrate, led to the proposal by Moyle and Mitchell [(1977) FEBS Lett. 84, 135-140] that there is a Ca2+(Sr2+)-3 hydroxybutyrate symporter in rat liver mitochondria. However, experiments described in the present paper support a different interpretation. Under the conditions of the experiments by Moyle and Mitchell, the rate of respiration and the poise of Sr2+ accumulation are mainly limited, not by delta mu H+, but by lack of respiratory substrate. Even though N-ethylmaleimide is a potent inhibitor of 3-hydroxybutyrate dehydrogenase, we have found that, somewhat surprisingly, under the special conditions of these experiments, sufficient 3-hydroxybutyrate dehydrogenase activity remains available to account for the 3-hydroxybutyrate dependent respiratory stimulation and Sr2+ import. PMID- 3086093 TI - Activity levels of mouse DNA polymerase alpha-primase complex (DNA replicase) and DNA polymerase alpha, free from primase activity in synchronized cells, and a comparison of their catalytic properties. AB - To asses the possible roles of the two active forms of mouse DNA polymerase alpha: primase--DNA-polymerase alpha complex (DNA replicase) and DNA polymerase alpha free from primase activity (7.3S polymerase), in nuclear DNA replication the correlation of their activity levels with the rate of nuclear DNA replication was determined and a comparison made of their catalytic properties. The experiments using either C3H2K cells, synchronized by serum starvation, or Ehrlich culture cells, arrested at the S phase by aphidicolin, showed DNA replicase to increase in cells in the S phase to at least six times that of the G0-phase cells but 7.3S polymerase to increase but slightly in this phase. This increase in DNA replicase activity most likely resulted from synthesis of a new enzyme, as shown by experiments using a specific monoclonal antibody, aphidicolin and cycloheximide. Not only with respect to the presence or absence of primase activity, but in other points as well the catalytic properties of these two forms were found to differ; DNA replicase preferred the activated calf thymus DNA with wide gaps of about 100 nucleotides long as a template-primer, while the optimal gap size for 7.3S polymerase was 40-50 nucleotides long. Size analysis of the products synthesized on M13 single-stranded circular DNA with a single 17 nucleotide primer by DNA replicase and 7.3S polymerase suggested the ability of DNA replicase to overcome a secondary structure formed in single-stranded DNA to be greater than that of 7.3S polymerase. PMID- 3086094 TI - Metabolism of 2-oxoaldehydes in yeasts. Possible role of glycolytic bypath as a detoxification system in L-threonine catabolism by Saccharomyces cerevisiae. AB - L-Threonine catabolism by Saccharomyces cerevisiae was studied to determine the role of glycolytic bypath as a detoxyfication system of 2-oxoaldehyde (methylglyoxal) formed from L-threonine catabolism. During the growth on L threonine as a sole source of nitrogen, a large amount of aminoacetone was accumulated in the culture. The enzymatic analyses indicated that L-threonine was converted into either acetaldehyde and glycine by threonine aldolase or 2 aminoacetoacetate by NAD-dependent threonine dehydrogenase. Glycine formed was condensed with acetyl-CoA by aminoacetone synthase to form 2-aminoacetoacetate, a labile compound spontaneously decarboxylated into aminoacetone. The enzyme activities of the glycolytic bypath of the cells grown on L-threonine were considerably higher than those of the cells grown on ammonium sulfate as a nitrogen source. The result indicated the possible role of glycolytic bypath as a detoxification system of methylglyoxal formed from L-threonine catabolism. PMID- 3086095 TI - Identification of an essential lysine residue in the phosphatidylcholine-transfer protein from bovine liver by modification with phenylisothiocyanate. AB - Modification by phenylisothiocyanate inhibits the phosphatidylcholine-transfer protein from bovine liver. Inhibition by this apolar reagent was greatly enhanced in the presence of vesicles, indicating that an effective modification of an essential lysine residue(s) from the interface may occur. Labeling with [14C]phenylisothiocyanate demonstrated that Lys55 was the major site of modification. We propose that Lys55 is part of the peptide segment that interacts with the membrane. PMID- 3086096 TI - Liposome-mediated delivery of antibody to a Drosophila cell line. AB - Large, unilamellar vesicles composed of equimolar amounts of acidic phosopholipids and phosphatidylethanolamine were able to deliver fluorescent dye [5(6)-carboxyfluorescein] or a monoclonal antibody directed against intermediate filament proteins to a Drosophila cell line (Kc cells). Millimolar Ca2+ or protamine sulfate in microgram quantities triggered rapid, synchronous delivery of either solute. Delivery required a specific lipid composition: liposomes composed of 1:1 mole ratios of phosphatidylethanolamine:phosphatidylserine were able to deliver their contents, but not if phosphatidylcholine was substituted for phosphatidylethanolamine. Light microscopic observation of Kc cells incubated with free dye or antibody alone showed very little uptake, a result indicating that encapsulation within liposomes is a prerequisite for substantial delivery. Moreover, the stability of adhering vesicles in the absence of calcium or protamine sulfate, the lipid specificity, and the rapid onset of intracellular fluorescence after triggering suggest that vesicle-cell fusion is the predominant mode of solute uptake. Fusion of liposomes with the cell membrane was confirmed by freeze-fracture electron microscopy, which showed liposome vesicles first adhering to cell surfaces, then undergoing fusion when calcium or protamine sulfate was added. PMID- 3086097 TI - Calcium regulation of ciliary activity in rabbit tracheal epithelial explants and outgrowth. AB - Ciliated epithelial cells from rabbit trachea were employed to examine the role of Ca2+ in the regulation of ciliary motility. Tracheal explants and outgrowths were maintained in culture, and ciliary frequency was determined using a photomultiplier interfaced with a spectrum analyzer capable of Fast Fourier transform analysis. Relative cellular Ca2+ levels were determined by measuring 45Ca2+ uptake and efflux. Elevated cellular Ca2+, from exposure to 10(-5) M calcium ionophore A23187, led to an increase in ciliary frequency followed by inhibition of motility after prolonged treatment. A decrease in ciliary frequency was observed upon lowering intracellular Ca2+ by exposing the epithelium to 1 mM EGTA. Exposure of ciliated cells to 10(-4) M trifluoperazine resulted in inhibition of ciliary motility, a result suggesting a possible role for calmodulin- or phospholipid-sensitive Ca2+-dependent protein kinases in ciliary function. These results support the hypothesis that intracellular Ca2+ is actively involved in modulating the frequency of ciliary beat. PMID- 3086098 TI - The localization of tau proteins on the microtubule surface. AB - The localization of porcine brain tau factor on in vitro assembled microtubules has been carried out by immunoelectron microscopy, using affinity-purified antibodies and protein A-gold particles. A parallel experiment was done using antibody against microtubule associated protein 2 (MAP2) and also a double labelling experiment using both antibodies with different sized gold particles. Our results indicate that, within the limits of resolution imposed by immunolabelling, the distribution patterns of tau factor and MAP2 on the microtubule are indistinguishable. PMID- 3086100 TI - Ventilatory response to CO2 in infants with alleged sleep apnoea. AB - Twenty-eight children whose parents reported sleep apnoea were investigated. In 15 infants apnoeic periods during sleep could be confirmed during clinical observation. Ventilatory responses to CO2 were measured in all infants, in 23 during sleep in 5 only when awake. A very wide range of CO2 sensitivities was found. In four children there was no ventilatory response or even a paradox one: a decrease in ventilation as PACO2 was increased. Two of these non-responding children died later, one still sleeps in a respirator aged three, and one developed a normal CO2 sensitivity a few months later. It is concluded that the parent's account of an apnoeic incident during sleep is not always reliable. A ventilatory response to CO2 is a useful tool with which to identify infants at risk of death, possibly related to a defective control of ventilation. The actual value of the CO2 sensitivity hardly gives any useful information, due to the wide range of "normal" reactions. No or negative ventilatory responses to CO2 seem to be indicators of high risk children, and may possibly play a role in SIDS incidents. PMID- 3086099 TI - A micro-autoradiographical study of the localization of 99mTc(Sn)-MDP and 99mTc MDP in undecalcified bone sections. AB - The localization of 99mTc(Sn)-MDP in bone tissue was compared with 99mTc-MDP by means of microautoradiography of undecalcified bone sections. Sections of good histological quality were obtained by a rapid embedding method in methylmethacrylate. No differences were found in the localization of these radiopharmaceuticals in fetal rat calvariae after incubation in vitro or in rat femora after administration in vivo. In the incubation experiment, hydrolyzed 99mTc was formed. The uptake was high in areas of new bone formation. No uptake was seen in cells or in resorbing areas. In compact bone 99mTc(Sn)-MDP was predominantly taken up in the vicinity of blood vessels. PMID- 3086101 TI - Effect of intravenous and intragastric fat infusion on intestinal brush border enzyme activities in rats. AB - Intralipid was given to adult rats for 4 days either by intragastric or intravenous infusion. The villus height, protein content and the levels of sucrase, lactase and aminopeptidase activities were determined in the jejunum. The results were compared to values found in control rats fed orally with an equilibrated isocaloric diet. Intragastric or intravenous infusion of Intralipid caused a 50% reduction in the protein content of the brush border membrane, a significant drop of the specific (expressed per milligram protein) and segmental (expressed per centimeter intestinal length) activities of the disaccharidases, the maintenance of aminopeptidase activity and the lengthening of the villi in the jejunum. The major loss in disaccharidase activities was obtained when fat was given intravenously. Arguments favoring a hormone-mediated effect of the infused lipids on the intestinal function are presented and discussed. PMID- 3086102 TI - Comparison of monoglyceryl acetoacetate and glucose as parental energy substrate after experimental trauma. AB - The effects of ketone bodies and glucose on nitrogen balance and liver protein synthesis were studied in rat after experimental trauma. Energy was delivered intravenously as either monoglyceryl acetoacetate (MA; 87.5% of total energy input) or glucose (G). The isocaloric infusions (132 kcal/kg/day) were started after recovery from anaesthesia and continued for 2 days. The liver protein synthesis was then measured in vitro by perfusion with 14C-leucine. The infusion of MA resulted in a more negative cumulative nitrogen balance (MA: -2.31 +/- 0.26 g N/kg, G: -1.32 +/- 0.43 g N/kg/48 h; mean +/- SD) and liver protein synthesis (MA: 43.4 +/- 17.2, G: 71.1 +/- 15.2; arbitrary units, mean +/- SD). The results indicate no benefits from MA during the immediate post-traumatic period. PMID- 3086103 TI - Sequential metabolic characteristics following portacaval shunt in rats. AB - A portacaval shunt (PCS) model is frequently employed to study phenomena inherent in portal-systemic shunting of splanchnic blood. In many species, a PCS induces hepatic insufficiency, accompanied by encephalopathy. Rats operated on with a 'nonsuture' technique tolerate a PCS better and exhibit no or only slight encephalopathy. Age and environment seem to have a large impact on the ability to tolerate a PCS. This explains the discrepancies between the results of different investigators and the varying time periods reported between the PCS operation and the optimal time for experiments. To characterize the PCS model (button technique) in rats with respect to metabolic parameters in our field of interest, we studied three groups of male Sprague-Dawley rats--non-operated (n = 12); sham operated (n = 12) and PCS (n = 13)--for 4 weeks following surgery. Body weight in the PCS group decreased for 1 week after surgery and then increased at about the same rate as in the control groups. Plasma immunoreactive insulin, plasma immunoreactive glucagon (IRG) and aromatic amino acid concentrations were highest 1 week after surgery and tended to normalize in the next weeks. Plasma branched chain amino acid (BCAA) concentrations were decreased in the 1st, 2nd and 3rd week after surgery, after which normalization occurred. These data demonstrate that after 3-4 weeks, male Sprague-Dawley rats start to recover from the metabolic disturbances caused by PCS with regard to the parameters measured. Therefore, experiments in this area, especially those relating to BCAA metabolism, should be carried out 2-3 weeks after the shunt operation (button technique). PMID- 3086104 TI - Sarcomas of the bladder and prostate: the role of immunohistochemistry and ultrastructure in diagnosis. AB - 2 undifferentiated malignant tumors of the bladder/prostate region (one with urinary schistosomiasis) and 6 carcinomas with spindle cell morphology were studied by immunohistochemical markers and electron microscopy. Our findings indicate that the categorization of undifferentiated tumors of this region is significantly aided by the use of such methods. PMID- 3086105 TI - Antihistamines: impaired performance and the tendency to sleep. AB - The central effects of various antihistamines were studied using a variety of tests of performance, including visuo-motor co-ordination and dynamic visual acuity, as well as paper and pencil tests and critical flicker fusion. The possible relationship between performance and sedation was also studied using digit symbol substitution and latencies to drowsy sleep. There was high degree of correlation between drowsiness, as indicated by the relative ease with which individuals fell asleep over the day, and impaired performance, but it was not possible to establish the relationship for each time of the day. These findings lend some support to the suggestion that impaired performance with antihistamines may be a non-specific effect of sedation. PMID- 3086106 TI - Alfentanil kinetics in renal insufficiency. AB - Alfentanil 100 micrograms/kg was administered as an i.v. bolus to 9 patients with severe chronic renal dysfunction (creatinine clearance 1.0 +/- 1.2 ml/min) requiring regular haemodialysis. Plasma alfentanil concentrations were measured by a specific radioimmunoassay. Individual plasma concentration-time curves were fitted to a two-compartment open model. Mean distribution and elimination half lives were 3.7 min and 58 min, respectively. The apparent volumes of distribution of the central compartment and the total volume of distribution at steady-state were 91 ml/kg and 304 ml/kg, respectively. Alfentanil plasma clearance was 5.3 +/ 2.5 ml/min/kg. All the patients tolerated alfentanil well and no side-effects nor delayed recovery were observed. PMID- 3086107 TI - Effects of 2,4-dinitrophenol on renal ammoniagenesis in the rat. AB - Injection of anesthetized rats with the uncoupling agent, 2,4-dinitrophenol (2,4 DNP) 10 or 20 mg/kg induced a systemic hyperammonemia unaccompanied by blood acid base status changes and related to an increased release of ammonium from the kidney into the renal vein. Ammonium excretion into the urine did not increase. The renal uptake of circulating glutamine rose. The antiepileptic drug sodium valproate (VPA), a short-chain, branched fatty acid, had the same effects on rat and man. These findings suggest that VPA stimulates renal ammoniagenesis by the same mechanisms as 2,4-DNP. PMID- 3086108 TI - Specific inhibition of PAF-acether-induced platelet activation by BN 52021 and comparison with the PAF-acether inhibitors kadsurenone and CV 3988. AB - BN 52021 is a chemically defined substance extracted from Ginkgo biloba leaves. Its inhibitory potency was tested on washed human platelets prepared so as to render them specifically sensitivity either to adenosine 5'-diphosphate (ADP), arachidonic acid (AA) or PAF-acether. Its activity and specificity were compared with those of two other reported inhibitors of PAF-acether effects: Kadsurenone and CV 3988. PAF-acether-induced aggregation of washed human platelets was concentration dependently inhibited by BN 52021 (IC50: 2.22 +/- 0.79 microM against 7.5 nM PAF-acether (n = 3)). Under the same experimental conditions the aggregation triggered by ADP was not modified and that induced by AA was marginally affected. The PAF-acether EC50 in platelet-rich plasma was increased 5 and 46-fold with 1 microM and 5 microM of BN 52021 respectively. This strongly suggested that the mechanism of action of BN 52021 is of the competitive type. Analysis of [3H]PAF-acether binding showed that BN 52021 as well as unlabelled PAF-acether prevented [3H]PAF-acether binding to intact washed platelets. In washed human platelets Kadsurenone affected only PAF-acether-induced aggregation (IC50: 0.8 +/- 0.4 microM (n = 3)), whereas CV 3988 inhibited the aggregation induced by ADP, AA and PAF-acether (IC50 were 10.2 +/- 2.3 microM; 2.2 +/- 0.1 microM; 1.0 +/- 0.1 microM respectively (n = 3). In contrast, up to 30 microM, CV 3988 was a specific antagonist of PAF-acether-induced platelet aggregation in plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086109 TI - Alteration of striatal dopaminergic functions implicated in methamphetamine induced reverse tolerance in rats. AB - Rats were injected repeatedly with methamphetamine (6 mg/kg per day, for 14 days). The effects of the repeated treatment on the change of behaviors and striatal DA metabolism induced by challenge with DA agonists were studied 10 days after the last injection. Repeated methamphetamine administration decreased the sedative effect of low dose apomorphine, and enhanced apomorphine-induced stereotyped behavior but reduced in after pretreatment with tetrabenazine. Striatal DA, HVA and DOPAC contents, and striatal gamma-butyrolactone-induced DA or DOPA accumulation were not altered by repeated methamphetamine treatment. The effect of apomorphine to decrease DA metabolite content and DA or DOPA accumulation was not changed either. As evidenced by experiments using alpha-MT, repeated methamphetamine administration increased DA utilization after methamphetamine or low dose apomorphine challenge, although it did not change DA utilization at the steady state (without drug challenge). These findings suggest that methamphetamine-induced reverse tolerance is accompanied by an increase of DA utilization resulting from the subsensitivity of DA utilization-modulating autoreceptors. PMID- 3086110 TI - Reversible induction of actin rods in mouse C3H-2K cells by incubation in salt buffers and by treatment with non-ionic detergents. AB - Incubating conditions which induced actin paracrystal-like intracellular structures (actin rods) were investigated by using several cell lines. We have found that an incubation of cells of a mouse fibroblastic cell line, C3H-2K, in an isotonic solution of NaCl containing 1 mM MgCl2, 1 mM CaCl2 and 10 mM MES, pH 6.5, induced disintegration of stress fibers and formation of actin rods in the cytoplasm. Actin rods were induced also by incubating in salt buffers in which Na+ of the above solution was substituted by most cations except K+ or Rb+. When the actin rod-forming cells were transferred back to DMEM containing 10% FBS, actin rods disappeared and stress fibers subsequently re-formed within 1 h at 37 degrees C. Although the induction was observed in NaCl buffer at a wide range of pH values (5.5-10), the optimal pH was 6.5. Formation of actin rods is dependent upon cellular metabolism, as it was inhibited at 4 degrees C, or by metabolic inhibitors. Incubation in NaCl buffer induced actin rods in HeLa, L, NRK, BALB/c 3T3 and Swiss 3T3 cells, but not in CEF or MEF cells. A decrease in cell volume was observed parallel with the induction of actin rods, except for CEF and MEF cells. Alterations in intracellular concentrations of Na, K or Ca were not correlated with the induction, however. Actin rods were also induced in C3H-2K cells by a brief treatment with non-ionic detergents. Tween 80 at concentrations as low as 0.003% was effective for the induction, but did not increase the passive membrane transport of p-nitrophenylphosphate. In contrast to the induction by NaCl buffer, treatment with Tween 80 induced numerous tiny actin rods at 4 degrees C, which became larger when further incubated at 37 degrees C. Double immunofluorescence staining with anti-actin antibody and anti-vinculin antibody showed that vinculin plaques remained at least in an early stage of the actin rod formation. We discuss the mechanism for the induction of actin rods based upon the present findings. PMID- 3086111 TI - Disturbances in DNA precursor metabolism associated with exposure to an inhibitor of poly(ADP-ribose) synthetase. AB - 3-Aminobenzamide (3AB) is widely used as an inhibitor of poly(ADP-ribose) synthetase to study the effect of protein ribosylation on various cellular processes, but the specificity of its inhibition has not been demonstrated. We found that 3AB has a wide range of effects on DNA precursor metabolism, as determined by high-performance liquid chromatographic separation of deoxynucleosides derived from enzymatic digestion of cellular DNA. 3AB (10-20 mM) significantly reduced cell growth in human lymphoblastoid cells. Furthermore, the incorporation of [3H]deoxycytidine into DNA was significantly enhanced relative to incorporation of [3H]deoxythymidine, [3H]deoxyguanosine, and [3H]deoxyadenosine. Incorporation of fragments of [3H]glucose into the pyrimidine fraction of DNA was significantly inhibited relative to incorporation into the purine fraction. At only 1 mM, 3AB had a major inhibitory effect on the incorporation of the methyl group from [3H]methionine into deoxyguanosine, deoxyadenosine, and deoxycytidine, with 50% inhibition into deoxyguanosine and deoxyadenosine and 90% inhibition into deoxycytidine. The specificity of 3AB inhibition to poly(ADP-ribose) synthetase is therefore doubtful in view of this variety of metabolic effects, involving pyrimidine synthesis and de novo synthesis via the one-carbon pool. PMID- 3086112 TI - Relationship of changes in spontaneous motor activity to spontaneous circling in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. AB - Two unilateral injections of 6-hydroxydopamine into the substantia nigra and ventral tegmental area of adult rats pretreated with desmethylimipramine produced severe unilateral depletions of limbic and striatal dopamine. These animals sustained global deficits in spontaneous motor activity with no recovery evident from 1 to 14 weeks postoperative. The frequency of spontaneous circling increased during the 1st few weeks postoperative and then remained stable during the last 2 months of observation. The changes in circling were independent of changes in global spontaneous motor behaviors. Biochemical determinations indicated an increased dopamine turnover in residual limbic and striatal dopamine neurons but with substantially changed dihydroxyphenylacetic acid:homovanillic acid ratios. The absence of functional recovery of both normal and asymmetric motoric behavior indicates that severe uncompensated deficits in motoric function produced by unilateral 6-hydroxydopamine lesions can provide a useful animal model for the study of dopaminergic contributions to movement disorders. PMID- 3086113 TI - Trypanosoma cruzi: isolate dependence in the induction of lytic antibodies in the mouse and rabbit. AB - Lytic antibodies able to interact with the live trypomastigotes of Trypanosoma cruzi have been associated with both protection and active infection. There are T. cruzi isolates unable to induce lytic antibodies despite their capacity in eliciting agglutinins and precipitins for immunofluorescent labeling. The host's spontaneous cure was ruled out as being responsible for negative results. The test performed either at 4 C or in the presence of sodium azide proved that negative lytic assays could not be attributed to capping phenomena. The classification of the parasites as T. cruzi was confirmed by their behavior in tissue culture and in the vector, as well as by the cross-protection exhibited by chronically infected mice against other lethal T. cruzi isolates. Cross resistance achieved by these mice also suggests that the host's protection during chronic infection is independent of the lytic antibody titer. PMID- 3086114 TI - Schistosoma mansoni: chemotherapy of infections of different ages. AB - Mice were treated with potassium antimony tartrate, hycanthone, oxamniquine, niridazole, or praziquantel at different times after infection with Schistosoma mansoni. The rate of cure was assessed by perfusion of surviving worms approximately 4 weeks after treatment, and the percentage reduction in worm burden was estimated relative to the number of adult worms perfused from control mice, comparably infected but untreated. All six drugs were relatively inactive against S. mansoni between 3 and 4 weeks after infection when compared with treatment at 5 to 6 weeks. However, the drugs differed in the patterns of cure they achieved in the 2-week period after administration of cercariae and in the period around the onset of patency. Worms that had been subjected to amoscanate or hycanthone in the third week after infection showed evidence of this as adults in having a reduced fecundity. Factors such as worm or host physiology, or host immune status may have had roles in the outcome of chemotherapy at different stages of maturation of S. mansoni. PMID- 3086115 TI - Schistosoma mansoni: salicylanilides as topical prophylactic against cercarial penetration of mice. AB - Salicylanilide and 37 of its analogs were applied topically to mice as candidate chemoprophylactic agents against Schistosoma mansoni cercarial penetration. The compounds were solubilized in absolute methanol, dimethyl sulfoxide, or isopropanol at concentrations not exceeding 1.25% W/V. The tails of the mice of each experimental group were treated by immersion for 5 min in the test compound solution or in the vehicle. The treated tails of 5 mice from each group were washed for 30 min in flowing tap water 3-4 hr after compound application. Tails of all mice were then exposed to approximately 100 cercariae by tail immersion for 1 hr, 24 hr after treatment. The portal veins were perfused 49 days after exposure and worm burdens were determined. The protective capacity of each compound was calculated by comparing the reduction of the mean worm burdens of the compound treated mice to the worm burdens of those treated with only the vehicle and expressing the resulting value as percentage protection. Of the 38 compounds tested, 20 provided 98% or better protection if the treated tails were not washed before exposure to cercariae. Of these 20 active compounds, 16 provided 98% or better protection from infection by S. mansoni cercariae even after the mouse tails were subjected to the 30 min wash. PMID- 3086116 TI - Diabetes alters drug metabolism--in vivo studies in a streptozotozin-diabetic rat model. AB - The influence of experimental streptozotozin-induced diabetes on hepatic drug metabolism in vivo has been studied in rats, using 14CO2-exhalation after 14C aminopyrine injection. Male diabetic rats showed a decreased (-18%), females an increased (+19%) 14CO2-exhalation compared to controls, indicating altered hepatic drug metabolism due to diabetes. PMID- 3086117 TI - [Effect of thiophosphamide on ceruloplasmin activity and the copper content of the blood of rabbits]. AB - Experiments were performed on rabbits 30 min, 6 hours, 1, 3, 7, 15 and 30 days after intravenous injection of thiophosphamide in a dose of 6 mg/kg body weight. The drug produced considerable changes in the activity of blood serum ceruloplasmin and blood copper content. The pattern of the changes in the enzyme activity and copper content depends on the time elapsed after the drug injection. PMID- 3086118 TI - [Mechanism of the contraceptive action of the triterpene glycosides from the rock jasmine Androsace septentrionalis L]. AB - The sum of triterpene glycosides of Androsace septentrionalis L. (a plant of genus Primula) was shown to change the concentrations of lutropin and follitropin in the hypophysis and plasma and the ratio of these hormones in the blood plasma in the active phase of the cycle. This leads to the change of the ovarian hormonal activity in the direction of predominance of the estrogenic action and an increase of the uterine contractile activity that can be of certain significance in manifestation of the contraceptive effect. PMID- 3086119 TI - [Corrective effect of gutimine on the body in hypoxia]. PMID- 3086120 TI - Relationship between structure and activity of aspirin-related compounds on the inhibition of in vitro platelet aggregation. AB - Thirteen aspirin-related compounds were tested for inhibitory activity on platelet aggregation in human platelet rich plasma (PRP) induced with ADP, collagen and arachidonic acid. The following structure-activity relationships were found: none of the functional groups used to replace the acetyl group retained the significant antiaggregant activity of aspirin; anti-aggregant activity was enhanced when the carboxylic group was replaced with a hydroxyl or an acetylated hydroxyl group. The activity of these mono and diacetylated pyrocatechol derivatives was unaffected by incubation of PRP with sodium salicylate. PMID- 3086121 TI - Alpha-subunits of Ns are released from the plasma membrane following cholera toxin activation. AB - Cholera toxin (CT) and islet-activating protein (IAP, a Bordetella pertussis toxin) were employed to test the hypothesis that GTP-binding regulatory proteins are released from plasma membranes to a greater extent when 'activated' than when 'inactivated'. CT, which activates Ns (the stimulatory GTP-binding regulatory protein of the adenylate cyclase system), catalyzed the incorporation of radioactivity from [32P]NAD into 45 and 47.5 kDa peptides associated with rat liver plasma membranes. Following ADP-ribosylation and centrifugation at 100000 X g for 1 h, approx. 30-35% of these CT-labelled peptides were no longer associated with the plasma membranes, but were recovered from the supernatant fraction. IAP, which inactivates Ni (the inhibitory GTP-binding regulatory protein of the adenylate cyclase system) catalyzed the incorporation of radioactivity from [32P]NAD into a 41 kDa peptide associated with the membranes. However, in contrast to the CT-labelled peptides, typically less than 5% of the IAP-labelled peptide was found in the 100000 X g supernatant fraction, but rather was almost exclusively associated with the membrane pellet. The data indicate that the alpha subunits of Ns are released from the plasma membrane following activation, and support the hypothesis that the beta gamma-subunits act to anchor the alpha subunits to the plasma membrane. PMID- 3086122 TI - Membrane protein-lipid hydrogen bonding: evidence from protein kinase C, diglyceride, and tumor promotors. AB - Membrane-bound proteins owe their retention and conformation in the lipid bilayer to hydrophobic peptide domains. Additional fixation, by protein-lipid hydrogen bonding, has been suggested, and recent reports on protein kinase C activation by diacylglycerol (DG) provide an unambiguous model for such bonding. The sn-1,2 diacylglycerol appears to donate a hydrogen bond from the sn-3 hydroxyl to the enzyme and to receive two hydrogen bonds, in the sn-1 and sn-2 ester CO groups, from the enzyme. This arrangement is confirmed in phorbol ester, a competitive inhibitor of DG for the kinase. This tumor promotor has a nearly identical spatial arrangement of hydrogen bond donor (9 alpha-OH) and acceptors (12 and 13 ester CO); so have two other tumor promotors, teleocidin and aplysiatoxin. There are reasons to believe that protein kinase C is not the only protein that is bound to membrane lipids by hydrogen bonding, and such bonding will have to be considered in membrane-associated events such as fusion, cross-membrane transport, or anesthesia. PMID- 3086123 TI - Potentiation and inhibition of secretion from neutrophils by phorbol ester. AB - We demonstrate that PMA exhibits multiple effects on fMetLeuPhe and ionophore mediated secretion from rabbit and human neutrophils: Inhibition of receptor mediated secretion appears to take place at an early stage in the stimulus secretion coupling sequence since PMA inhibits the formation of phosphatidate. Protein phosphorylation is observed with both PMA and fMetLeuPhe and the extent of phosphorylation is additive in the presence of both stimuli. Another possible site of regulation by PMA lies distal to the rise in cytosolic Ca2+. This is indicated by the enhancement of inhibition by PMA of the A23187-induced secretory response at low and high external Ca2+ concentrations, respectively. PMID- 3086124 TI - Immunochemical study of the plasma low and high density lipoproteins in Tangier disease. AB - Major disturbances of the lipoproteins in Tangier serum have been investigated using electrophoretic and immunochemical techniques. Previously described anomalies concerning the striking deficiency in HDL and the very low levels of apo A-I and apo A-II in Tangier patients are illustrated and explained. Anomalies concerning the fast LDL of Tangier serum are attributed to different forms of apo B not previously described. These data are strengthened by the features of a 2 dimensional electrophoresis method elaborated in the laboratory which allows apoproteins to separate in the second dimension. These apoproteins are obtained by the delipidation of the lipoproteins fractionated in a first polyacrylamide discontinuous gel. This method clearly shows the distribution of apoproteins in the first lipoprotein track and is in perfect accordance with the new concept of lipoprotein particles. PMID- 3086125 TI - Reticulocyte lipoxygenase, ingensin, and ATP-dependent proteolysis. AB - Lipoxygenase purified from rabbit reticulocyte lysate has a molecular mass of 68 kDa on SDS gel and a pI of 5.97. Lipoxygenase is inhibited by nordihydroguaiaretic acid (NDGA), 3-amino-1-(m-(trifluoromethyl)phenyl)-2 pyrazoline (BW755C), 5,8,11,14-eicosatetraynoic acid (ETYA), salicylhydroxamate (SHAM) or hemin. Metal ions or nucleotides do not affect its activity. The addition of certain of these inhibitors to the reticulocyte extract also inhibited the ATP-dependent proteolysis of casein, one of the distinct characteristics of reticulocytes. No clear correlation between lipoxygenase activity and ATP-dependent proteolysis could be detected. Hemin and NDGA inhibited both processes, but the concentrations necessary for inhibition were quite different. SHAM completely inhibited lipoxygenase, but not proteolysis. o Phenanthroline inhibited ATP-dependent proteolysis, but had no effect on lipoxygenase activity. We have also purified a high-molecular-mass protease, ingensin, from reticulocyte extract. This protease accounted for more than 90% of the casein-degrading activity in reticulocyte extract. NDGA inhibited ingensin at the same concentrations required for inhibition of ATP-dependent proteolysis. These results suggest that lipoxygenase is not indispensable for the ATP dependent proteolysis and the novel high-molecular-mass protease, ingensin, may be involved in the process. PMID- 3086126 TI - Organization of citric acid cycle enzymes into a multienzyme cluster. AB - The possibility that some of the enzymes of the citric acid cycle may be loosely associated into a multienzyme cluster has been investigated using extracts prepared by gentle disruption of cells. Gel filtration and sucrose density gradient centrifugation have shown that five sequential enzymes of the cycle specifically associate into a cluster: fumarase, malate dehydrogenase, citrate synthase, aconitase and isocitrate dehydrogenase. Ultrasonication destroys the abilities of the enzymes to associate. The cluster could catalyse the sequence of reactions leading from fumarate to oxoglutarate and has been found in extracts of several bacterial species as well as rat liver mitochondria. PMID- 3086128 TI - Low concentrations of the stable prostaglandin endoperoxide U44069 stimulate shape change in quin2-loaded platelets without a measurable increase in [Ca2+]i. AB - Dose-response relationships for raised cytoplasmic free calcium concentration, [Ca2+]i, and shape change were measured simultaneously in quin2-loaded human platelets. With the calcium ionophore ionomycin the threshold [Ca2+]i for shape change was 300 nM with a maximal response at 800 nM. With 1 mM external Ca2+ the U44069 concentrations required to stimulate half-maximal shape change and an increase in [Ca2+]i were 2 and 41 nM, respectively. For PAF these values were 8.7 and 164 pg/ml, respectively. Low concentrations of U44069 and PAF evoked substantial shape change without any rise in [Ca2+]i. In the absence of external Ca2+, U44069 stimulated half-maximal shape change at 2 nM, and half-maximal elevation of [Ca2+]i at 69 nM: here, increased [Ca2+]i never reached the threshold [Ca2+]i for shape-change derived with ionomycin. These results suggest that some transduction mechanism other than elevated [Ca2+]i, as yet unidentified, can cause shape change. PMID- 3086129 TI - Luteinizing hormone and follicle-stimulating hormone responses to intransal gonadotropin-releasing hormone. AB - For determination of the dose-response relationships of plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to the intranasal administration of gonadotropin-releasing hormone (GnRH), normal adult men were administered doses of 100, 200, 400, and 800 micrograms of GnRH on separate days, and plasma LH and FSH were measured before and after nasal insufflation of GnRH. Plasma LH was increased after a minimum dose of 200 micrograms GnRH. Median peak plasma LH levels occurred 30 minutes after intranasal GnRH and followed a log dose relationship. When compared with intravenous GnRH, the biopotency of intranasal GnRH at the 200-, 400-, and 800-microgram doses was 1.1%, 2.3%, and 6.2%, respectively. Plasma FSH levels rose significantly only after the highest (800-micrograms) intranasal GnRH dose. From these data, we conclude that in eugonadal adult men the minimal effective dose of intranasal GnRH to elicit a significant pituitary (LH) response is 200 micrograms and that the relative efficacy of intranasal GnRH increases with the dose. In spite of the apparently low biopotency for intranasal GnRH, this route of administration may be considered as an alternative to the parenteral mode of GnRH delivery, and the lower biopotency can be partly overcome by increasing the dose. PMID- 3086127 TI - Calcium-dependent association of 33 kDa protein in polymorphonuclear leukocytes with phospholipid liposomes containing phosphatidylserine or cardiolipin. AB - The effects of lipids and Ca2+ on the association of cytoplasmic proteins of polymorphonuclear leukocytes (PMN) with dipalmitoylphosphatidylcholine liposomes containing phosphatidylserine (PS) or cardiolipin (CL) were examined. In the presence of Ca2+, a cytoplasmic protein (33 kDa) of PMN was found to be a major component that bound to these liposome membranes. The maximum association with the liposomes was obtained at the molecular concentration of 25% CL and 50% PS; the required concentrations of Ca2+ were in the nanomolar and micromolar ranges for CL and PS, respectively. The liposome-associated 33 kDa protein was released from liposomes by an addition of EGTA. These results suggest that the 33 kDa protein reversibly associates to the cytoplasmic surface of PMN plasma membranes where PS localizes depending on a small change in intracellular concentration of free Ca2+. PMID- 3086130 TI - Sustained intrauterine release of levonorgestrel over five years. AB - Two models of levonorgestrel-releasing intrauterine devices were studied. Model A was designed to deliver 20 micrograms/day, and model B was designed to deliver 30 micrograms/day. Plasma concentrations of levonorgestrel were determined in blood samples taken from women who used the levonorgestrel-releasing intrauterine devices (IUDs) and who participated in a clinical trial for more than 5 years. During clinical studies IUDs have been removed for various reasons between 8 and 40 months after insertion. The rate of release of levonorgestrel from the IUDs was calculated by determining the remaining amount of levonorgestrel. Plasma concentrations of levonorgestrel ranged between a mean +/- standard deviation (SD) concentration of 166 +/- 75 pg/ml and 131 +/- 32 pg/ml for the first 18 months of use and between 101 +/- 37 pg/ml and 74 +/- 15 pg/ml at 24 and 60 months after insertion of the IUD. The plasma concentrations from 24 months through 60 months were significantly lower than concentrations measured during initial months of IUD use, but not between the two devices. There was a strong correlation between the time of use and the amount of levonorgestrel lost from the IUDs. The calculated mean daily release of levonorgestrel was 17.6 micrograms for model A and 22.2 micrograms for model B. This gives a calculated lifetime of more than 6 years for a levonorgestrel-releasing IUD. PMID- 3086131 TI - The value of ultrasonographic endometrial measurement in the prediction of pregnancy following in vitro fertilization. AB - This work was undertaken for evaluation of the value of endometrial thickness as an early predictor for the success of in vitro fertilization (IVF). Endometrial changes were evaluated ultrasonographically in 47 women undergoing IVF. A high dose gonadotropin protocol was used for induction of multiple follicular development. Thirty-seven women did not conceive following the procedure (group I), and 10 conceived (group II). Ultrasonographic endometrial measurements were performed repeatedly throughout the cycle. Serum 17 beta-estradiol and progesterone levels were evaluated concomitantly. Three consecutive growth patterns of the endometrium were observed. The first was a rapid one with a daily growth rate of about 0.5 mm from approximately 9 mm on day -3 to 12 mm on day +2 (day 0 being the day of human chorionic gonadotropin administration). The second phase, following follicular aspiration, showed a decrease in growth rate to about 0.1 mm per day until day +11, when a thickness of about 13 mm was measured. In group I growth was arrested from day +11 until menstruation, whereas in group II an accelerated growth rate of about 0.4 mm per day could be demonstrated from day +14 onward. Endometrial growth did not correlate with serum estradiol or progesterone levels. No conception occurred with an endometrial thickness below 13 mm on day +11. It is concluded that endometrial thickness follows a distinct pattern of growth in human menopausal gonadotropin-induced cycles and does not correlate with serum sex hormones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086132 TI - Positive correlation between the level of protein-carboxyl methylase in spermatozoa and sperm motility. AB - Levels of protein-carboxyl methylase (PCM) activity were measured in spermatozoa from infertile patients with less than 50% sperm motility and compared with those of normal fertile controls. When spermatozoa were washed by a standard centrifugation procedure, the level of PCM activity in a subgroup of patients with sperm motility ranging from 0% and 20% (24.0 +/- 5.2 pmol/mg protein, mean +/- standard error of the mean) was significantly different from that of controls (35.9 +/- 2.3 pmol/mg). However, when the entire population of patients with sperm motility ranging from 0% to 50% (32.6 +/- 6.2 pmol/mg) was compared with controls, no significant difference was observed in sperm PCM levels. With this standard washing procedure no significant relationship (r = 0.28; P greater than 0.05) between sperm PCM activity and motility was observed. By contrast, when spermatozoa were washed on a Percoll gradient, to eliminate other cellular elements, both groups of patients with 0% to 20% (14.6 +/- 2.5 pmol/mg) and with 0% to 50% (21.5 +/- 2.4 pmol/mg) sperm motility had sperm PCM levels significantly lower than that of controls (34.7 +/- 3.6). A highly significant relationship (r = 0.78; P less than 0.001) was observed between the levels of sperm PCM activity and motility. PMID- 3086133 TI - Induction of ovulation in the postpartum rhesus monkey: factors determining success in obtaining primate luteal tissue. AB - Ovulation induction in the postpartum rhesus monkey was attempted with the use of purified human pituitary gonadotropins for assessment of (1) whether this procedure could be used to provide a source of luteal tissue; (2) the extent of ovarian responsiveness to gonadotropic stimulation; (3) factors that might facilitate ovulation induction during the peurperium; and (4) factors that might be a contributory cause of induction failure. Twenty rhesus monkeys were treated with purified human follicle-stimulating hormone (hFSH) and human luteinizing hormone (hLH) twice daily, beginning on days 0, 10, or 20 postpartum, with or without prior administration of bromocriptine. Laparotomies were performed during the midluteal phase. Ovaries were examined, and all corpora lutea were removed. Neither the day of beginning the gonadotropin treatment nor bromocriptine administration had a significant effect on the success rate of ovulation induction, which averaged 60% overall. Inductions begun during July had a significantly (P less than 0.025) lower success rate than those started at other times of the year. Antibodies to hFSH and hLH were detected in serum from monkeys that had undergone ovulation induction. Antibodies to hFSH, but not hLH, were associated with significantly reduced induction success (P less than 0.05). Plasma estradiol rose in response to gonadotropin treatment, and the induced follicular phase averaged 13.6 +/- 0.7 days. In all animals judged to have ovulated, corpora lutea were observed at laparotomy, and plasma concentrations of progesterone were significantly elevated (13.8 +/- 3.8 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086134 TI - Direct biphasic effects of danazol on gonadotropin-dependent differentiation of cultured rat granulosa cells. AB - The direct effects of danazol on granulosa cell differentiation were studied in vitro over a broad concentration range with a primary culture of rat granulosa cells. Whereas treatment with low-dose (defined herein as less than 10(-6) M) danazol by itself was without significant effect on basal steroid secretion, combined treatment with low-dose danazol (10(-7) M) and a minimally effective dose of follicle-stimulating hormone (FSH, 20 ng/ml) resulted in a substantial augmentation of the FSH effect. Although independent of the FSH dose employed, the effect of danazol proved dose- and time-dependent, with an apparent median effective dose of 3.6 +/- 0.3 X 10(-8) M. In contrast, high-dose danazol (defined herein as greater than 10(-6) M) produced dose-dependent inhibition of FSH (250 ng/ml)-supported steroid secretion. Taken together, our findings indicate that the effects of danazol on granulosa cell differentiation may be biphasic in nature, displaying a stimulatory low-dose component, followed by inhibition at higher dose levels. PMID- 3086135 TI - Decreased gestational sac volumes in pregnancies induced by human menopausal gonadotropin. AB - Mean gestational sac volumes of 9 singleton pregnancies induced by human menopausal gonadotropin (hMG) measured by ultrasound were compared with mean gestational sac volumes obtained from 37 normal singleton pregnancies, 6 to 8 weeks from the last menstrual period. HMG-induced gestational sacs were smaller at 6 and 7 weeks of gestation, compared with normal pregnancies. Despite the initial lag in gestational sac volume, hMG-induced pregnancies subsequently demonstrated appropriate fetal growth as measured by crown-rump length measurements between 8 and 12 weeks. These pregnancies also demonstrated normal fetal growth patterns in the second and third trimesters of pregnancy, as assessed by clinical evaluation and ultrasound. These preliminary data suggest that early growth development in hMG-induced pregnancies may be different from that in spontaneously occurring pregnancies. PMID- 3086136 TI - Enlargement of hydrosalpinges during ovarian stimulation protocols for in vitro fertilization and embryo replacement. PMID- 3086137 TI - [Microcirculation in the mesentery of rats on a protein-free diet and parenteral feeding with nitrogen preparations in toxic hepatitis]. PMID- 3086138 TI - [Changes in sexual functioning in the male rat after total or anterior deafferentation of the mediobasal hypothalamus]. AB - After complete deafferentation of the mediobasal hypothalamus in male rats, the luteinizing hormone content increased in the blood which correlated with an increasing of testosterone secretion, weight of seminal glands and additional sexual organs. Half of the operated animals preserve copulating ability. The content of folliculo-stimulating hormone in the blood of animals after the complete deafferentation was decreased, particularly in non-copulating males. After the interior deafferentation of the mediobasal hypothalamus in the rats, the luteinizing hormone and testosterone contents in the blood did not change but the weight of seminal glands and concentration of folliculo-stimulating hormone in the blood decreased. The data obtained suggest different mechanisms of control of the luteinizing and folliculo-stimulating hormones secretion in male rats, the connection of the mediobasal hypothalamus with anterior hypothalamus and preoptic area being necessary for normal secretion of the folliculo-stimulating hormone. PMID- 3086139 TI - [Hydrolases of the digestive organs during ontogenesis]. AB - A wide variety of enzymes actualizing membrane hydrolysis of nutrients and their distribution in the gastro-intestinal tract were characterized in one-day old and adult rats and rabbits. The comparison of enzymatic activities of various animal species suggests that some enzymes are responsible for the adaptation to milk diet (lactase), others--to definitive nutrition (invertase, maltase). A number of enzymes (peptidase, alkaline phosphatase) do not depend on the type of nutrition. High activity of some hydrolases in the colon has been demonstrated confirming the A. M. Ugolev hypothesis of its digestive functions in the early ontogenesis. PMID- 3086140 TI - [Functions of the stomach after parasympathetic denervation of the fundus and uncoupling of the fundus and antral portions]. AB - Selective proximal vagotomy (SPV) evoked the same alterations in the motility of fundal part of the dog stomach as truncal vagotomy. Within 2-3 months the fundal motility was completely normalized. If the SPV were carried out with preserved innervation in the cardial zone, the motility restoration was accelerated to 7-10 days. But is SPV was added to the disconnection of antral part with proximal stomach, its motility did not restore at all. SPV initially suppressed the insulin secretion to 70-85 per cent; in 6-12 months this suppression decreased to 60 per cent and stabilized on this level. The Auerbach plexus seems to differ from the Meissner plexus in that the former can transfer the gaval influence from the innervated zone into the denervated one. Judging by the functional indices the growth of vagal fibers from the innervated zone into the denervated one did not take place. PMID- 3086141 TI - [Classification of asymptomatic autoimmune thyroiditis by thyrotropin-releasing hormone loading]. AB - Thyrotropin-releasing hormone loading was performed on 91 patients with asymptomatic autoimmune thyroiditis. Four women had no response to this loading test and had high levels in serum total and free thyroxine (TT4, FT4) and in serum total and free triiodothyronine (TT3, FT3). These patients might be classified as subclinical hyperthyroidism (Group G). Twenty-four patients had normal levels of both basal and peak thyrotropin after loading and were classified as Group I. There were no significant differences between 45 controls (Group C) and Group I patients in serum thyroid hormone levels. Patients with normal basal and high peak levels of thyrotropin were included in Group II. The number of patients in this group was 53. The mean levels of basal and peak thyrotropin were 4.8 microU/ml and 39.6 microU/ml, respectively, and were significantly higher than in Group C and Group I (P less than 0.005). In 10 patients classified as Group III with high levels of both basal and peak thyrotropin, serum concentrations of TT4, FT4 and FT3 were significantly lower than in the other groups (P less than 0.025); however, significant differences in TT3 could not be seen among them. Serum cholesterol levels gradually increased from Group C to Group III. There were significant differences between Group C and Group II (P less than 0.05). PMID- 3086142 TI - [The role of the sympathetic nervous system and adrenals in hemodynamic changes after intracerebroventricular administration of 5-hydroxytryptamine in rats]. AB - Recently, the role of the serotonergic nervous system has been implicated in blood pressure regulation and in the pathogenesis of hypertension. However, the effects of 5-hydroxytryptamine (5-HT) administration on hemodynamics have been notoriously inconsistent and the precise mechanism of the blood pressure regulation of the serotonergic nervous system has not been elucidated yet. In our previous study, we demonstrated that the intracerebroventricular (i.c.v.) administration of 5-HT in rats elicited consistent pressor response with concomitant increase in plasma norepinephrine and that the pressor response was abolished by systemic pretreatment of phenoxybenzamine or by serotonin receptor antagonist, methysergide. The purpose of this experiment is to investigate further the relationship between the sympathetic nervous system and the serotonergic nervous system. PMID- 3086143 TI - Lupus anticoagulants. PMID- 3086144 TI - DRG legislation and the physician. PMID- 3086145 TI - Ovarian failure without gonadotropin elevation in a patient with post-traumatic isolated hypogonadotropic hypogonadism. AB - A woman with secondary amenorrhea following head trauma showing isolated gonadotropin deficiency of hypothalamic origin did not respond to massive doses of hMG therapy (11 250 IU daily dose). Ovarian biopsy showed the absence of follicles, despite persistently low FSH levels. In this case the occurrence of premature ovarian failure was only suspected from the lack of response to hMG and diagnosed by ovarian histology. PMID- 3086146 TI - Acylation and carbamylation of equine muscle carbonic anhydrase (CA-III) upon reaction with p-nitrophenyl esters and carbamoyl phosphate. AB - Equine muscle carbonic anhydrase (CA-III) behaves like ubiquitin in undergoing extensive acylation of N epsilon-lysine residues upon reacting with p-nitrophenyl esters. The enzyme undergoes extensive carbamoylation of lysine residues when reacted with carbamoyl phosphate. The modification of from 6 to 7 lysine residues results in the production of a series of more anodic electrophoretic components. The derivatization of the lysine residues leads to a marked decrease in the enzyme's ability to hydrate CO2. The equine CA-III possesses both acid and alkaline phosphatase activities in contrast to the rabbit which possesses only the former type. PMID- 3086147 TI - Aggregation-dissociation and stability of acid beta-galactosidase purified from porcine spleen. AB - Sucrose gradient centrifugation of the monomeric form (A1) of porcine spleen beta galactosidase showed a pH-dependent equilibrium between monomer at neutral pH (pH 7.0) and dimer at acidic pH (pH 5.4-3.0), independent of ionic strength. While the oligomeric form (Ao), which was hardly dissociated under physiological conditions, was dissociated only with some protein denaturing agents into similar catalytic subunit to the A1. Both the A1 and Ao were equally active and stable at acidic pH, in the physiological condition inside lysosome (around pH 4.6). PMID- 3086148 TI - Characterization of the human syncytiotrophoblast plasma membrane associated components. AB - A purification procedure of synctiotrophoblast plasma membrane (STPM) has previously been described. We now report a further characterization of their associated components. By immunochemical analysis two groups of proteins were found. The first fraction solubilized by chaotrope treatment was made up with a complex of IgG, albumin, transferrin and alpha-fetoprotein. The second fraction, insolubilized by KCl-treatment but by detergents, did not react with antisera to human proteins; it contained human chorionic gonadotropin and placental lactogen. The amino acid, carbohydrate and lipid content of STPM were determined. High galactosyl- and sialyl-transferase activities were found in purified STPM. The role of these various components on the acceptance of the fetal allograft is discussed. PMID- 3086149 TI - Comparison of the metabolic behavior of rat apolipoproteins A-I and A-IV, isolated from both lymph chylomicrons and serum high density lipoproteins. AB - Rat apolipoprotein (apo) A-I and A-IV, isolated from both lymph chylomicrons and serum high density lipoproteins (HDL) were analyzed by isoelectric focusing. Lymph chylomicron apo A-I consisted for 81 +/- 2% of the pro form and for 19 +/- 2% of the mature form, while apo A-I isolated from serum HDL was present for 36 +/- 4% in the pro form and for 64 +/- 4% in the mature form. Apo A-IV also showed two major protein bands after analysis by isoelectric focusing. The most prominent component is the more basic protein that amounts to 80 +/- 2% in apo A IV isolated from lymph chylomicrons and to 60 +/- 3% in apo A-IV isolated from serum HDL. Apo A-I (or apo A-IV), isolated from both sources (lymph chylomicrons or serum HDL), was iodinated and the radioactive apolipoproteins were incorporated into rat serum lipoproteins. The resulting labeled HDL was isolated from serum by molecular sieve chromatography on 6% agarose columns and injected intravenously into rats. No difference in the fractional turnover rate or the tissue uptake of the two labeled HDL preparations was observed, neither for apo A I nor for apo A-IV. It is concluded that the physiological significance of the extracellular pro apo A-I conversion or the post-translational modification of apo A-IV is not related to the fractional turnover rate in serum or to the rate of catabolism in liver and kidneys. PMID- 3086150 TI - Further studies on the size and composition of the chick embryo fibroblast cytosolic DNA complex. AB - The chick embryo fibroblast cytosolic DNA complex shows anomalous elution behaviour on agarose gel column chromatography. The indicated molecular size varies between 5 X 10(5) dalton (higher exclusion limit gels) and 1.4 X 10(6) dalton (lower exclusion limit gels). Chromatography on lower exclusion limit gels shows the [3H]thymidine labelled (DNA) complex as a sharp peak, coincident with a peak of [3H]uridine and [3H]lysine labelling and similar pulse labelling patterns for the three precursors but with DNA labelling lagging behind RNA and protein. Both cultured and uncultured cell cytosols show an A260 peak coincident with the [3H]precursor labelling peaks. PMID- 3086151 TI - Intracellular calcium distribution in pigeon erythrocytes. AB - Subcellular compartmentation of calcium has been studied in digitonin-treated pigeon erythrocytes. The following calcium pools could be detected: A non vesicular and tightly bound pool of calcium able to reach values equivalent to 5 mumol calcium/ml cells that required millimolar calcium concentrations. A vesicular calcium pool with high calcium affinity that had properties similar to mitochondrial calcium transport. Extracellularly added ATP was strongly hydrolyzed by intact pigeon erythrocytes in the presence of either magnesium or calcium. The hydrolysis of ATP was not coupled to fluxes of either 45Ca2+ or 86Rb+ and most probably took place inside the cells. PMID- 3086152 TI - Comparison of fatty acid patterns of polar and neutral lipid classes and cyclo oxygenase activity in taste and non-taste epithelium of steer tongues. AB - Epithelial tissues and papilla from several regions of the steer tongue were isolated and the fatty acids from each lipid class in the polar and neutral fractions were assayed. The observed profiles indicated regional differences. Arachidonic acid and other fatty acids containing long carbon chains (greater than 22) were found in all tissues sampled, particularly in the phosphatidyls of the inositols, ethanolamines, cholines, and in the cholesterylesters. Production of prostaglandin E2 was measured through cyclo-oxygenase activity and the presence of plasmalogens was observed in the phosphatidylethanolamine and choline fractions. Higher rates of PGE2 synthesis and greater amounts of plasmologens were found in taste-related epithelial samples compared to lingual epithelial control samples not containing taste buds. The heterogeneity of patterns of lipids and fatty acids found in the epithelium of the tongue suggests possible zonal specialization to satisfy regional physiological needs. PMID- 3086153 TI - Analogues of folate antagonists as affinity and fluorescent probes of dihydrofolate reductase structure and function. PMID- 3086154 TI - Prodrugs in cancer chemotherapy. PMID- 3086155 TI - The rational design of suicide substrates of amine oxidases. PMID- 3086156 TI - Gonadotropin regulation of Leydig cell DNA synthesis. AB - Adult male rats were injected s.c. with either saline, 100 IU hCG, 100 micrograms FSH, 50 micrograms LH, 100 micrograms PRL, 50 micrograms estradiol-17 beta, 500 micrograms or 10 mg testosterone; 50 micrograms estradiol-17 beta; animals were sacrificed at 12-120 h post-injection. Collagenase-dispersed interstitial cells (150-200 X 10(6) cells/2 ml) were incubated in vitro with 10 microCi [3H methyl]thymidine for 1 h at 32 degrees C. Centrifugation of the cells on discontinuous 11-27% metrizamide gradients revealed thymidine incorporation in the regions of population I and II Leydig cells. A significant increase in thymidine incorporation into DNA after treatment with either hCG or LH was first detectable at 48 h, was equivalent to control values at 72 h and was again significantly increased at 96 h in population I and at 120 h in population II cells. [3H]Thymidine incorporation at 48 h, expressed as dpm/10(6) cells, was 2205 +/- 432 and 4119 +/- 929 vs. 16473 +/- 3795 and 11648 +/- 3427 for control and hCG-treated population I and II cells, respectively. Addition of 20 mM hydroxyurea suppressed [3H]thymidine incorporation, 97% and 96% in hCG-treated population I and II cells, respectively. Autoradiographic analyses revealed that nuclei from control and 48 h hCG-treated population I and II cells exhibited 1.2% and 2.3% vs. 7% and 6.8% silver grains, respectively. PRL had no influence on LH/hCG-enhanced DNA synthesis; however, estradiol-17 beta administration for 48 h dramatically suppressed thymidine incorporation. Population I Leydig cells exhibited a higher level of LH/hCG-stimulated DNA synthesis compared to population II cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086157 TI - Normalizing effect of Ca2+ ionophore on cytoplasmic Ca2+ and parathyroid hormone release of dispersed parathyroid cells from patients with hyperparathyroidism. AB - The effects of the Ca2+ ionophore A23187 on parathyroid hormone (PTH) secretion and cytoplasmic free Ca2+ concentration (Ca2+i) were measured at different extracellular Ca2+ concentrations using dispersed cells from patients with hyperparathyroidism (HPT). The addition of a low concentration of the Ca2+ ionophore to quin2-loaded cell preparations resulted in the apparent normalization of calcium-regulated Ca2+i. At all extracellular calcium concentrations Ca2+i reached significantly higher values in the presence of the ionophore and the dose-response relationship was shifted to the left. Under similar conditions calcium-regulated PTH release was correspondingly corrected with an increased suppressibility and left-shifted dose-response relationship. The data render strong support for a disturbed regulation of Ca2+i as a major factor in the pathophysiology of HPT. PMID- 3086158 TI - Differences in long-term effects of L-glutamine and D-glucose on insulin release from rat pancreatic islets. AB - We have compared the effects of long-term exposure to L-glutamine or D-glucose on nutrient-induced insulin release from pancreatic islets of the rat. After 3 days of culture islets were finally tested in 1 h incubations for insulin responses to 16.7 mM of glucose, glutamine, leucine or a combination of leucine and glutamine. After culture at 11 mM glucose + 2 mM glutamine (A), glucose, leucine and glutamine stimulated release to a similar extent from islets. After culture at 1.7 mM glucose + 10 mM glutamine (B), only leucine stimulated insulin release. After culture at 11 mM glucose + 10 mM glutamine (C), both leucine and glutamine increased the insulin response. After culture at 1.7 mM glucose and 2 mM glutamine (D), only glutamine slightly stimulated release. After culture in high glutamine (B or C), a combination of leucine and glutamine significantly inhibited release as compared to leucine alone. A switch in culture media from B to A for 1 h prior to final incubations revived insulin release in response to glucose but not to glutamine. The reverse switch (A to B) abolished both subsequent glucose-and glutamine-induced insulin release. A switch from D to B revived an insulin response to leucine. Exposure of B-cells to 11 mM glucose during 30 min in another experimental system (perfused pancreas) induced a significant insulin response to subsequent stimulation with glutamine; this response was, however, only 17% of that to glucose per se observed in the same experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086159 TI - The effects of inhibin purified from bovine follicular fluid in several in vitro pituitary cell culture systems. AB - The effects of inhibin purified from bovine follicular fluid (bFF) and a charcoal treated bFF preparation were investigated in several inhibin in vitro systems based on the use of pituitary cells in culture. FSH, LH, TSH and PRL were determined in the medium and cell extracts before and after a 4 h LHRH stimulation test. Both pure inhibin and bFF preparations markedly inhibited the basal release, cell content and LHRH-stimulated release of FSH in a parallel dose dependent manner with minor or negligible effects on LH, TSH and PRL. Using parallel line bioassay statistics the inhibin activities of the purified inhibin preparations in the various in vitro systems were calculated with the charcoal treated bFF as standard. Significantly higher inhibin values were obtained using the basal release procedure than with the cell content or LHRH-stimulated release procedures. This difference was influenced by the length of time the inhibin preparations were in culture. The highly purified preparations showed no signs of cytotoxicity in culture as assessed by a 51Cr release test. It is concluded that purified bFF inhibin is specific in suppressing pituitary FSH and not LH, TSH or PRL. The observation that purified bFF inhibin is more active in the basal release procedure is attributed to a loss of activity of the bFF standard in this system in contrast to that observed in either the cell content or LHRH-stimulated release procedure. PMID- 3086160 TI - Polyamines and growth regulation of cultured human breast cancer cells by 17 beta oestradiol. AB - The growth of ZR-75-1 cells, a line of human breast cancer cells in culture, is stimulated by oestradiol and inhibited by anti-oestrogens. Changes in growth rate caused by these agents are accompanied by changes in activity of ornithine decarboxylase, a rate-limiting enzyme for polyamine synthesis. Furthermore, the growth inhibition caused by tamoxifen, an anti-oestrogen, can be reversed by the addition of spermine, spermidine or putrescine to the cells. Insulin can also stimulate ZR-75-1 cell growth and this is again accompanied by an increase in ODC activity. The reduced cell growth rate observed when the cells become confluent is associated with a marked decrease in ornithine decarboxylase activity. Experiments performed with DFMO, a specific and irreversible inhibitor of ODC, show that this compound can prevent the stimulation of growth by oestradiol and that this may be overcome by the addition of putrescine to the cells. It would appear that increased ODC activity and polyamine synthesis are necessary components of the stimulation of breast cancer cell growth by oestradiol but that other growth regulatory stimuli also may act via this enzyme. PMID- 3086162 TI - A method for the mass isolation of islets from the adult pig pancreas. AB - A method for mass isolation of islets from the pig pancreas is described. The procedure involves the use of an enzymatic and mechanical pancreatic digestion procedure followed by filtration and separation of the islets on Ficoll gradients. A remarkably high yield of purified islets has been obtained from the pig pancreas with this procedure. The islets are morphologically intact and respond to acute stimulation with glucose in vitro. PMID- 3086161 TI - Ecdysteroid-regulated heat-shock gene expression during Drosophila melanogaster development. AB - Peaks in hsp 26, 28, and 83 RNA levels are correlated with peaks in ecdysteroid titers during mid-embryogenesis, pupariation, and mid-pupation, and with a peak in the level of RNA from the 74EF ecdysone puff at pupariation. Inhibition of the ecdysteroid peak at pupariation by temperature shift of the conditionally ecdysteroid-deficient strain ecd-1 was followed by a disappearance of hsp 26 RNA and a decline in hsp 83 RNA level; subsequent addition of exogeneous 20-OH ecdysone to the temperature-shifted strain resulted in a severalfold increase in hsp 83 RNA level, and a dramatic increase in that of hsp 26. These results are consistent with the induction of the hsp 83, 28, and 26 genes by ecdysteroid at several developmental stages. PMID- 3086163 TI - In vivo regulation of liver and skeletal muscle glycogen synthase activity by glucose and insulin. AB - The regulation of liver and skeletal muscle glycogen synthase by plasma insulin and glucose has not been investigated in vivo at physiological blood glucose concentrations. We have, therefore, used the glucose clamp technique to investigate the effects of these variables independently in rats. Short-term streptozocin-(0.15 g/kg) diabetic animals were used in addition to normal rats to avoid endogenous insulin secretion during hyperglycemic clamps. In normal and diabetic animals, 3 h of hyperinsulinemia without change in blood glucose concentrations caused only a small increase in liver glycogen synthase activity (+34%), whereas hyperglycemic clamps at 6.0 and 10.0 mmol/L resulted in marked increases (+268 and +394% of basal, P less than 0.001). Liver glycogen concentrations at the end of the clamps reflected these changes. In skeletal muscle, glycogen synthase was increased by +58% by the euglycemic hyperinsulinemic clamp and was not increased significantly further by hyperglycemia. Similarly, muscle glycogen concentration increased with the 4.0 mmol/L clamp but during the hyperglycemic clamps was only raised more in direct proportion to blood glucose concentrations. The results confirm that blood glucose concentration is the major short-term regulator of glycogen synthase activity in the liver but that insulin is of prime importance in skeletal muscle. PMID- 3086165 TI - Mechanism of stimulation of liver glycogen synthesis by fructose in alloxan diabetic rats. AB - In diabetic animals and humans, stimulation of liver glycogen synthesis has been reported after administration of a large parenteral fructose load. The effects of an oral fructose load have not been examined previously. In the diabetic state, glycogen synthase phosphatase activity is reduced, and synthase D (the inactive form) is a poor substrate for the phosphatase. Thus, activation of synthase to the synthase R and synthase I (R + I) (active) forms by fructose would not be expected. We have determined that oral fructose administration does stimulate glycogen synthesis and have examined the mechanism by which this is accomplished. In 24-h-fasted alloxan diabetic rats, basal liver glycogen was higher than in normal rats (8.3 +/- 1.8 vs. 3.0 +/- 0.5 mg/g wet wt). After fructose (4 g/kg) was given, the initial rate of glycogen synthesis was normal in diabetic rats, but total glycogen synthesis was reduced. By 240 min, liver glycogen increased to 18 +/- 4.0 mg/g wet wt in diabetic rats versus 30.5 +/- 1.5 mg/g wet wt in normal rats. Synthase R + I was low and did not increase significantly (0.063 +/- 0.006 to 0.064 +/- 0.010 U/g wet wt) after fructose administration to the diabetic animals. Phosphorylase a did not decrease significantly during the period of active glycogen synthesis. In the diabetic rats, glucose-6-phosphate increased by 84% (0.103 +/- 0.010 to 0.184 +/- 0.020 mumol/g wet wt) within 10 min and remained elevated above the control level. UDPglucose decreased from 0.336 +/- 0.013 to 0.271 +/- 0.011 mumol/g wet wt at 10 min and remained below the control level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086164 TI - Acetone metabolism in humans during diabetic ketoacidosis. AB - Plasma acetone turnover rates were measured with the primed continuous infusion of 2-[14C]acetone in patients with moderate to severe diabetic ketoacidosis. Plasma acetone turnover rates ranged from 1.52 to 15.9 mumol X kg-1 X min-1 (108 1038 mumol X 1.73 m-2 X min-1) and were directly related to the plasma acetone concentrations that ranged from 0.47 to 7.61 mM. The average acetone turnover rate was 6.45 mumol X kg-1 X min-1 (533 mumol X 1.73 m-2 X min-1), a value twice that obtained in a similar group of diabetic ketoacidotic patients via the single injection technique of 2-[14C]acetone administration. Degradation of urine glucose revealed that 14C from administered 2-[14C )acetone was principally located in carbons 1, 2, 5, and 6 of the glucose molecule in five of six patients. This distribution is similar to that expected from 2-[14C]pyruvate, suggesting that acetone was converted to glucose through pyruvate. In one patient, label was located predominantly in glucose carbons 3 and 4, indicating that acetone metabolism may be different in some patients. Acetol (1 hydroxyacetone) and 1,2-propanediol (PPD), two possible metabolites of acetone, were detected in plasma of the patients. The concentrations of Acetol ranged from 0 to 0.48 mM and of PPD ranged from 0 to 0.53 mM. The concentrations of each metabolite were directly related to the plasma acetone concentrations. During the continuous infusion of 2-[14C]acetone, the specific activities of plasma glucose and PPD rose continuously but did not reach constant values. Estimates of the minimal percent plasma glucose and PPD derived from plasma acetone averaged 2.1 and 74%, respectively. PMID- 3086166 TI - EDTA solutions for the dissolution of calcium bilirubinate stones. AB - The calcium chelating of different EDTA solutions was investigated after addition of 5.49% calcium bilirubinate powder. Calcium chelating seems to be an essential step in disaggregation of pigment stones. We found that Ca chelating is pH dependent and that the system must be buffered in order to prevent pH shifting during the dissolution process. When an alkaline (pH 9.4), buffered 1% EDTA solution is mixed with bile in a ratio of 70:30, dissolution of Ca will decrease to 60% as compared to investigations without bile. Furthermore, we could demonstrate that the EDTA solution would not only dissolve Ca bilirubinate powder, but complete bovine pigment stones of homogeneous structure and mostly inhomogenously composed stones of man as well. PMID- 3086167 TI - Nontraumatic rhabdomyolysis during diabetic ketoacidosis. AB - The frequency of nontraumatic rhabdomyolysis in diabetic ketoacidosis was investigated by serial measurements of the serum levels of myoglobin and the serum activity of creatine kinase isoenzyme MM in 12 consecutively admitted ketoacidotic patients. In 5 patients (Group 1) we found hypermyoglobinaemia and elevated activity of creatine kinase isoenzyme MM on admission to hospital, whereas these two variables were normal in 7 patients (Group 2). On admission significantly higher median blood glucose levels and higher median serum osmolality were found in Group 1 than in Group 2 (for blood glucose: 49.6 mmol/l versus 19.0 mmol/l, p less than 0.02; for serum osmolality: 360 mosm/kg H2O versus 315 mosm/kg H2O, p less than 0.05). Decreased renal function was found in Group 1 as reflected by significantly higher beta 2-microglobulin serum concentrations in Group 1 compared with Group 2 on admission (median values 4.1 mg/l versus 1.7 mg/l, p less than 0.01) and during the first 3 days of therapy. The serum concentration of hypoxanthine (an indicator of the cellular energy state) was elevated in all patients on admission, with no difference between patients with or without hypermyoglobinaemia. In conclusion, our findings suggest that nontraumatic rhabdomyolysis with hypermyoglobinaemia and elevated serum activity of creatine kinase isoenzyme MM may be a hitherto unrecognized common feature of diabetic ketoacidosis. PMID- 3086168 TI - Effect of exercise on protein turnover in muscles of lean and obese mice. AB - The effect of work-induced hypertrophy on skeletal muscle protein metabolism was studied in lean mice and in mice rendered obese with goldthioglucose. After tenotomy of the gastrocnemius muscle, the adaptative growth of soleus muscle was less pronounced in obese than in lean mice. Protein turnover was studied in the isolated soleus muscle 4 days after the operation. Tyrosine incorporation in total proteins and tyrosine release in the incubation medium (indices of protein synthesis and degradation) were increased by 3- and 2-fold in overloaded (i.e. work-induced hypertrophied) muscles of lean and obese mice, respectively, compared to the control muscles isolated from the non-operated leg. The qualitative modifications in the pattern of proteins synthetized from 35S methionine were identical in both groups of mice. This increase in protein turnover in overloaded muscles results from an increased rate of polypeptide chain initiation (3-fold in lean mice, 2.2-fold in obese mice) without any modification of peptide chain elongation rates. Work-induced hypertrophy was also able to reverse the defect in amino acid uptake which is present in soleus muscles of GTG-obese mice. These results suggest that the work-induced increase of skeletal muscle protein turnover is diminished in obese mice. PMID- 3086169 TI - Internalization of 3H-glibenclamide in pancreatic islet cells. AB - As judged by autoradiographic criteria at the optical level, rat islet cells progressively accumulate 3H-glibenclamide over 1 to 30 min incubation at 24 degrees C. The labeled material associates with all endocrine cells, but is preferentially seen within B cells. The total uptake of 3H-glibenclamide (1.0 mumol/l) is little affected by the presence of unlabeled glibenclamide (0.2 mmol/l), but is significantly decreased at 4 degrees C (p less than 0.05). At the electron microscopic level, less than 15% of the autoradiographic grains are located at the B cell plasma membrane and 72-79% of the grains found over the cytoplasm are associated with insulin secretory granules. Such a pattern is observed both after short (1 min) or prolonged (30 min) incubation, and at 4 or 24 degrees C. It is proposed that the insulinotropic action of glibenclamide is not necessarily attributable to primary events located solely at the cell surface. PMID- 3086170 TI - The effect of pregnancy and lactation on the disposition of [2,4,2',4' 14C]tetrachlorobiphenyl in the mouse. AB - The disposition of 150 mg/kg 2,4,2',4'-tetrachlorobiphenyl (4-CB) administered intraperitoneally as a function of nonpregnant body weight was studied in virgin, late pregnant, and early postpartum mice and their offspring. Highest concentrations of the polychlorinated biphenyl (PCB) were observed in adipose tissue and mammary gland regardless of reproductive state. Concentrations of 4-CB equivalents in the tissues examined, however, differed among the three groups, possibly due to the alterations in lipid deposition/mobilization associated with pregnancy and lactation. Approximately 20% of 14C activity was eliminated from carcasses of virgin mice at 4 days after 4-CB administration. No significant decrease in carcass 14C content was observed during this 4-day interval in late pregnant animals. Minimal transplacental transfer of 14C activity occurred (approximately 1% of total maternal body burden) but 4-CB was rapidly eliminated in breast milk to nursing offspring. Ninety percent of total carcass 14C activity was eliminated from lactating mice over a 4-day period, approximately 75% of which could be accounted for in neonatal carcasses. This indicates milk to be the preferred route of elimination for this PCB congener in postpartum animals. Virtually all radioactivity recovered from milk comigrated with parent compound following thin-layer chromatographic analysis. A comparison between hepatic microsomal ethoxycoumarin-O-deethylase activity (ECOD) and liver concentrations of 14C activity showed that pregnant animals were less responsive to the inducing effects of 4-CB than virgin or postpartum mice. This diminution in response may be, in part, responsible for the lack of elimination of 4-CB equivalents from the late pregnant animal during the 4-day experimental period. PMID- 3086171 TI - Relationship of alterations in energy metabolism to hypophagia in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - Efficiency of energy utilization was evaluated temporally in 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD, 50 micrograms/kg)-treated male their pair-fed counterparts, and a group with ad libitum access to ground feed. TCDD-treated rats exhibited a progressive reduction in feed intake and body weight. The weight loss of vehicle-treated rats, pair-fed to the TCDD-treated group, was comparable to that found in rats receiving TCDD. Following treatment, rats administered TCDD were as efficient in absorbing feed energy from the gut as control rats. This was evidenced by similar relative relative digestible energy values in TCDD-treated rats, their pair-fed partners, and a group with ad libitum access to feed. Equivalent decreases in oxygen consumption and carbon dioxide production in TCDD treated rats and their pair-fed counterparts, relative to rats with ad libitum access to feed, suggested that the decrease in both of these parameters in TCDD treated rats was secondary to hypophagia and/or weight loss. Decline of respiratory quotient (RQ) to almost 0.7 in both TCDD-treated rats and their pair fed counterparts is indicative of fat combustion. By Day 17 post-treatment, RQ increased significantly in the TCDD-treated and pair-fed groups possibly due to a limitation in the availability of lipid stores. Also, TCDD-treated rats and their pair-fed partners diminished their water intake to a similar extent without reducing urine output. Likewise, urinary excretion of both energy and urea was decreased to the same extent in rats treated with TCDD as it was in their pair fed counterparts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086172 TI - Measurement of semen quality, fertility, and reproductive hormones to assess dibromochloropropane (DBCP) effects in live rabbits. AB - Thirty-six sexually mature Dutch rabbits were divided into six equal groups to receive in the drinking water 5 days/week for 10 weeks 0, 0.94, 1.88, 3.75, 7.50, and 15.00 mg of DBCP/kg body wt. General health, body weight, semen quality (four ejaculates per male per week), and libido were measured throughout. Fertility, blood follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were measured the last week and cauda epididymal sperm were examined at sacrifice. There was no effect of DBCP on general health or body weight. There was considerable variation in ejaculate volume, percentage motile sperm, and sperm concentration per milliliter within groups and among weeks. However, between the first 2 weeks and the last 2 weeks of the experiment sperm output had increased by 19% in the three lower DBCP groups and decreased by 16% in the three higher DBCP groups (p less than 0.01). The proportion of sperm with abnormal tails also increased as DBCP dosage increased. Fertility was unaffected. FSH was elevated (p less than 0.01) in the group receiving 15 mg/kg of DBCP, which is consistent with the impairment of spermatogenesis. Libido, LH, and testosterone levels were not affected. Sperm morphology was the most sensitive indicator of a DBCP effect in the live animal, being affected at a daily oral intake greater than or equal to 1.88 mg DBCP/kg body wt. PMID- 3086173 TI - Valproic acid teratogenicity in mice after various administration and phenobarbital-pretreatment regimens: the parent drug and not one of the metabolites assayed is implicated as teratogen. AB - The antiepileptic drug valproic acid (VPA) was administered via four different routes in the mouse during gestational stages sensitive for interference with neural tube defect formation: a single oral intubation or injection, sc or ip, on Day 8, or infusion via subcutaneously implanted osmotic minipumps from Day 7 1/2 to 8 1/2 of gestation. Embryotoxicity was evaluated on Day 18 (incidence of exencephaly, embryolethality and fetal weight retardation). Oral intubation of VPA resulted in significantly lower peak concentrations of VPA as well as lower embryotoxicity as compared to sc and ip administration. The metabolites of the beta-, omega- and omega-1 oxidation pathways were present in both maternal serum and gestational tissues in very low concentrations (usually less than 2% of corresponding VPA levels). Infusion of VPA via osmotic minipumps (lower steady state VPA levels as compared to peak levels following injection of VPA) resulted in embryolethality and fetal weight retardation, but little exencephaly. The metabolic pattern was similar in all four administration experiments. Phenobarbital pretreatment of the dams (previously shown to reduce VPA serum concentrations and induce the omega- and omega-1 oxidation pathways) reduced the embryotoxicity of VPA. These results suggest that VPA embryotoxicity is mediated by the parent drug, and not one of the metabolites considered in this study. PMID- 3086174 TI - Pharmacologic evaluation of various metabolites and analogs of valproic acid: teratogenic potencies in mice. AB - A number of metabolites of the anticonvulsant drug valproic acid (VPA) as well as related substances were tested in regard to their teratogenicity in the mouse following single sc injections of 600 mg/kg on Day 8 of gestation. VPA was highly teratogenic at this dose level and over 60% of live fetuses had neural tube defects (exencephaly). Homologous compounds with shorter or longer alkyl chains were less teratogenic. Substitution of the alpha-H atoms in related branched carboxylic acids by methyl or ethyl groups abolished the teratogenic response. Introduction of a double bond in the omega-position of VPA (4-en-VPA) did not change the teratogenicity of VPA, while omega-2 double bond (2-en-VPA) abolished teratogenicity. The other VPA metabolites tested as well as two straight-chain acids (n-octanoic acid and 4-pentenoic acid) and the two clinically used substances valpromide (valproic acid amide) and ethosuximide did not induce neural tube defects, although some of them induced slightly increased resorption rates and fetal weight retardation. The serum protein binding capacities of the various compounds did not correlate with the teratogenic response. Also the concentrations reached in the gestational material did not predict the teratogenicity of the substances tested. Our results indicate that the teratogenicity of the class of compounds studied represents a more specific effect than the anticonvulsant activity which could lead to the development of alternative antiepileptic drugs with low embryotoxic potential. PMID- 3086175 TI - Transformation of inferior vena caval thrombosis to membranous obstruction in a patient with the lupus anticoagulant. AB - A 24-yr-old woman with hemolytic anemia developed multiple thrombosis of the hepatic vein and inferior vena cava. She was found to have circulating lupus anticoagulant that could have been causally related to the thrombosis and hence the Budd-Chiari syndrome. On her first admission to the hospital vena cava and hepatic vein catheterizations revealed partial thrombotic occlusion of the cava at the level of the diaphragm, which was subsequently transformed into complete membranous obstruction. The right hepatic vein, which was patent on the first admission, was also completely occluded. These observations support the theory that membranous obstruction of the inferior vena cava is a sequela to inferior vena caval thrombosis rather than a congenital anomaly. PMID- 3086176 TI - Pneumoperitoneum complicating endoscopy in a patient with duodenal and jejunal diverticula. PMID- 3086177 TI - Cytoprotection by a synthetic prostaglandin against ethanol-induced gastric mucosal damage. A double-blind endoscopic study in human subjects. AB - This randomized, double-blind, placebo-controlled study compared the cytoprotective effects of misoprostol, a synthetic analog of prostaglandin E1, and cimetidine on ethanol-induced gastric mucosal damage. Forty-five healthy male subjects were accepted, following endoscopy to exclude those with upper gastrointestinal disease. Injury to the gastric mucosa was induced by spraying it with 80% ethanol solution. Misoprostol (200 micrograms) intragastrically or cimetidine (300 mg) orally or placebo was administrated before the ethanol challenge. The gastric mucosa was graded using a seven-point endoscopic scale by two endoscopists 15 and 30 min after ethanol instillation. Thirty minutes following the instillation of ethanol, the gastric mucosa of placebo-treated subjects showed marked damage, with an endoscopic score (mean +/- standard deviation) of 5.5 +/- 0.9. Cimetidine partially prevented gastric mucosal damage, with an endoscopic score of 4.5 +/- 1.7 as compared to placebo (p = 0.04). Misoprostol significantly prevented gastric mucosal injury with a mean endoscopic score of 1 +/- 1.7 when compared to placebo (p = 0.0001) and to cimetidine (p = 0.0002). This cytoprotective action of misoprostol may prove to be clinically very important and warrants further investigation. PMID- 3086178 TI - Observations on the discharge of the secretion from ependymal cells of the subcommissural organ (SCO) of some South American primates. AB - The secretion of the subcommissural organ (SCO) is synthesized in the intrinsic cells of that structure, a neuroendocrine gland. The organelles involved in the synthesis of this secretion are rough-surfaced endoplasmic reticulum (RER) and the Golgi apparatus. It is still uncertain whether and to what extent the latter participates in the synthesis. In highly active secretory ependymal cells of the SCO, the Golgi apparatus exhibits distinct signs of intense activity. This suggests that the Golgi apparatus is involved in the preparation of the secretion, even if this is difficult to prove electron microscopically. The secretion is discharged from the optical part of the SCO-cells into the cerebrospinal fluid (CSF) of the IIIrd ventricle, where Reissner's fibre is formed. Different phases of release of the content of the secretory granula into the IIIrd ventricle are described; our findings are in agreement with previously published observations. In 2 cases delicately granulated and moderately electron dense material was found in circumscriptly dilated vaults of the intercellular spaces. Release of secretory material into intercellular spaces appears to be possible, but is evidently infrequent. Regular occurrence of a basal (peripheral) discharge into the hypendymal capillaries is not unanimously agreed upon as yet. In this paper, a passage of granula is described from the cytoplasm of the end feet of SCO cells through the walls of the capillaries into the systemic circulation. This provides structural evidence that secretory material synthesized in the SCO is released into the capillaries. These observations must ultimately be confirmed with the aid of ultracytochemical methods, particularly using labelled material. PMID- 3086179 TI - [Puberty and ovarian function following cytostatic therapy in childhood]. AB - Chemotherapy for malignant disease can cause gonadal dysfunction. However, little is known about the reversibility and severity of these effects in girls treated during childhood or puberty. For this reason we investigated clinical data and endocrine parameters (FSH, LH, PRL, E2, progesterone) of 51 adolescent females. Our clinical data showed that intermittent pulse chemotherapy as administered to most patients with solid tumours leads to a more pronounced growth retardation than continuous low dose chemotherapy as given to patients with leukemia and lymphomas. Girls treated prior to menarche failed to start menstruation while on chemotherapy, but all had their menarche shortly after cessation of the treatment. Most of the girls treated post menarche developed amenorrhoea, whereas some had irregular cycles unless they were on a very mild drug regimen. From the endocrinous data we concluded that primary ovarian failure was rare and occurred in adolescent girls only after a combination of chemotherapy and radiotherapy. In girls with regular menstrual cycles after treatment a high incidence of anovulation or an inadequate luteal phase could be observed. The latter symptoms may be signs of hypothalamic ovarian failure as caused by stress, anxiety and emotions associated with a malignant disease. PMID- 3086180 TI - [Neurofibromatosis and pregnancy]. AB - A case of neurofibromatosis (Recklinghausen's disease) in pregnancy in a 29-year old patient is reported. The woman has had two uncomplicated pregnancies and deliveries. The lesions of the neurofibromatosis did not change during the course of the pregnancy. However, based on the few published cases it is necessary to pay attention to hypertension or an exacerbation of the neurofibromatosis. PMID- 3086181 TI - Genetic analysis of the right (3') end of the rosy locus in Drosophila melanogaster. PMID- 3086182 TI - Nucleotide sequence and derived amino acid sequence of a cDNA encoding human muscle carbonic anhydrase. AB - We report the nucleotide (nt) sequence of a full length cDNA clone, pCA15, which encodes the human muscle-specific carbonic anhydrase, CAIII. pCA15 identifies a 1.7-kb mRNA, which is present at high levels in skeletal muscle, at much lower levels in cardiac and smooth muscle and which appears to be developmentally regulated. The CAIII mRNA is distinguished by a 887-nt long 3'-untranslated region, containing two AAUAAA signal sequences and is longer than either of the mRNAs encoding the erythrocyte CAs, CAI and CAII, which each have relatively shorter 3'-untranslated regions, 360 and 670 nt long, respectively. The derived amino acid (aa) sequence for human CAIII shows 85% homology with ox CAIII, 62% homology with human CAII and 54% with human CAI when simple pairwise aa comparisons are made. We describe an allelic variation at a TaqI restriction site for CAIII which occurs at high frequency in the European population. PMID- 3086183 TI - Prostaglandin and thromboxane biosynthesis in resting and activated platelet-free monocytes from aged subjects. AB - The main cyclo-oxygenase-dependent arachidonic acid (AA) derivatives, i.e. prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), have been measured by radioimmunoassay in platelet-free cultures of human monocytes from young and old subjects, in presence and in absence of activating substances (10% fetal calf serum). No difference was found between cells from the two groups as far as the production of PGE2 and TXB2 (stable metabolite of TXA2) was concerned, at variance with reported data in young and old experimental animals. The addition to the cultures of exogenous AA caused a reorientation of cyclic endoperoxide metabolism resulting in a consistent decrease of the ratio TXB2/PGE2, but only in monocytes from young subjects. The data are discussed with respect to the claimed role of prostaglandins in the age-related immune derangement which is present in aged humans. PMID- 3086184 TI - Intravitreal argon and carbon dioxide laser, and xenon arc photocoagulation in vitreoretinal surgery. AB - Argon laser, carbon dioxide laser, and xenon arc endophotocoagulators have been used intravitreally to produce chorioretinal lesions during the course of the vitrectomy procedure. The advantages and disadvantages of each method of endophotocoagulation are presented. Both the argon laser and the xenon arc have a fiber optic delivery system. The carbon dioxide delivery system has a series of quartz waveguides transmitted through a miniature articulating arm. The advantages of using a carbon dioxide laser are its dual quality to act as both a photocoagulator and phototransector, its lack of pigment dependence, and its ability to deposit its energy in a well-defined area without adverse effects on neighboring ocular tissue. PMID- 3086185 TI - Tyrosinase activity in human ocular malignant melanoma. AB - We examined tyrosinase activity in pigmented specimens from three cases of ocular malignant melanoma. Tissue (cholate-trypsin-treated) extract was prepared in cholate-phosphate buffer by homogenization, centrifugation, trypsin digestion, and hydroxylapatite column chromatography. Tyrosinase activity was spectrophotometrically assayed as dopa (L-3,4-dihydroxylphenylalanine) oxidase activity. Tyrosinase activity was detected in the cholate-trypsin-treated extracts. Enzyme activity was inhibited by phenylthiourea but not by 3-iodo tyrosine. The enzyme was inactivated when extract was preheated or digested with pronase. We believe that our findings confirm the presence of tyrosinase activity in ocular malignant melanoma. PMID- 3086186 TI - Congenital ocular and other systemic abnormalities associated with ring-11 chromosome. AB - The ocular and systemic abnormalities in a boy with ring chromosome 11 [46, XY/46, XY, r(11) (p 15.5----q25] are described. The ocular anomalies consisted of bilateral hypermetropia, microcornea, anterior chamber cleavage syndrome with prominent Wolfflin nodes, and cartwheel configuration of the anterior iris leaf. The systemic changes consisted of skeletal, muscular and articular defects, obesity, cryptorchidism, and mild mental retardation. PMID- 3086188 TI - The effects of a community-based long term care project on nursing home utilization. PMID- 3086189 TI - Concurrent weekly cis-platinum and radiotherapy in advanced cervical cancer: a preliminary dose escalating toxicity study. AB - Concurrent weekly cis-platinum in a dose escalating manner and conventional radiotherapy was evaluated in advanced cervical cancer. The toxicity of weekly cis-platinum given 2 hr before standard fractionation of radiotherapy was assessed using the modified GOG toxicity criteria. Sixteen patients having parameters indicating high risk for conventional therapy failure including positive pelvic and paraaortic nodes and intraperitoneal spread were entered. There was no life-threatening toxicity. The toxicity of the administered chemotherapy was only moderate. Patient compliance was good as at the 20 mg/m2 dose level, 79% of the prescribed doses were administered. The use of adjuvant cis-platinum in poor prognosis advanced cervical cancer merits further study. PMID- 3086187 TI - Selective and reversible breakdown of the tight junctional barrier in the rabbit ciliary body induced by arachidonic acid. A tracer and freeze-fracture study. AB - Arachidonic acid induced a reversible breakdown of the blood-aqueous barrier in the iridial processes of the rabbit ciliary body, whereas the ciliary processes were not affected under the conditions of this study. The focal passage of horseradish peroxidase through the tight junctions was demonstrated. In freeze fracture images, this breakdown of the barrier function was associated with focal changes: an alteration in the geometry of the tight junctional network; an increase in the number of discontinuities of the P-face ridges and particles and short bars in the E-face furrows; an increase in the density of intramembranous particles within the junctional area. The significance of the ultrastructural alterations of the tight junctions as a structural counterpart of the physiological changes is discussed. PMID- 3086190 TI - The influence of surgical staging on the evaluation and treatment of patients with cervical carcinoma. AB - Ninety-six patients with cervical cancer underwent surgical staging prior to radiation therapy. An equal number of patients were explored by transperitoneal and extraperitoneal surgery. Three different extraperitoneal approaches were utilized. All patients had bilateral paraaortic lymphadenectomy and selective pelvic nodal sampling. Intraperitoneal cytology and selected biopsies were performed. A 52% correlation existed between clinical and surgical staging. Radiotherapeutic treatment decisions were subsequently based on findings at operative staging. Nine percent of patients undergoing transperitoneal staging experienced a small bowel injury after radiation requiring surgical correction. No patients undergoing extraperitoneal surgery experienced postradiation small bowel morbidity. Extended field radiation was administered to 17% of patients, and a 30% five-year disease-free survival rate was observed. Although prognostic stratification is enhanced with surgical staging, using current radiotherapy techniques, the majority of patients with paraaortic nodal metastases will fail treatment. Based on our experience, only 2.5% of patients in a Stage IIB-IVA category will benefit from radiotherapeutic treatment decisions made as a consequence of staging laparotomy. PMID- 3086191 TI - Clear cell adenocarcinoma (CCA) of the vagina and cervix in association with pregnancy. AB - The effect of pregnancy on patients with CCA of the vagina and cervix was evaluated based upon a review of 503 cases. Eighty-five had been pregnant (24 at diagnosis), 408 had never been pregnant, and the pregnancy history was unavailable in 10 cases. All of the 24 patients pregnant at diagnosis were over 16 years of age; 14 were in the first trimester, 6 in the second, and 4 in the third trimester. By FIGO criteria, 15 were stage I, 7 stage II, and 2 were stage III. The 24 pregnant and 408 never pregnant (age corrected) cases were compared with regard to maternal hormone history, symptoms, stage, location, predominant histologic or cell type, greatest tumor diameter, surface area, depth of invasion, grade, and number of mitoses. No significant differences were detected. Twelve of the 24 pregnant patients had radical hysterectomy with or without irradiation (9 stage I, 3 stage II); of the 7 treated by local therapy (5 stage I, 2 stage II), 3 required additional therapy due to persistent disease; 4 had radiotherapy alone (1 stage I, 2 stage II, and 1 stage III); one had teletherapy followed by exenteration (stage III). Six of the 24 died 2 to 12 years after diagnosis (1 stage I, 3 stage II, 2 stage III). Eighteen are alive at 1 to 17 years. The overall 5 and 10 year actuarial survival rates (age adjusted) for the group pregnant at diagnosis (86 and 68%) do not differ significantly from the never pregnant group. Pregnancy does not seem to adversely affect the outcome of CCA. Guidelines are presented to treat pregnant patients with CCA. PMID- 3086192 TI - The prognostic significance of the minimum thickness of uninvolved cervix in patients with cervical carcinoma stages IB, IIA, and IIB. AB - The minimum thicknesses of uninvolved cervical tissues at the sites of deepest tumor invasion were evaluated in 899 patients with Stage IB, IIA, and IIB cervical carcinoma. Minimum thicknesses were greater than or equal to 10 mm in 126 (14%), 5-10 mm in 247 (27%), and less than 5 mm in 335 (38%) patients. Parametrial extension was found in 191 (21%) patients. Nodal metastasis rates were 6, 10, 22, and 55%, respectively. Patients with greater than or equal to 10 mm thicknesses did not have two or more positive nodes (P less than 0.05). The proportion of patients with two or three positive nodes increased from 3 to 10% (P less than 0.005) as the minimum thickness decreased from 5-10 to less than 5mm. The proportion of patients with four or more positive nodes increased from 3 to 22% (P less than 0.001) in cases in which tumor invaded the parametrial tissues. Five-year disease-free rates were 99, 93, 88, and 65%, respectively. Each percentage decrease was significant (P less than 0.05, 0.05 less than P less than 0.01, and P less than 0.001). These results indicate that uninvolved cervical thickness is a good indicator of nodal metastases, number of positive nodes, and patient prognosis. PMID- 3086194 TI - [New aspects in myopia development--models in experimental animals--a literature review]. PMID- 3086193 TI - Inhibition of thrombin-catalyzed reactions in blood coagulation and platelet activation by heparin fractions in the absence of antithrombin III. AB - The antithrombin-III-independent effect of heparin was studied in the following thrombin-catalyzed reactions: activation of purified plasma factor V and partially purified plasma factor VIII:C, generation of factor Va from the platelets and, in the presence of collagen, of the platelet procoagulant activity. Five heparin fractions and a heparinoid were compared to crude heparin. Crude heparin was a more potent inhibitor of these reactions than the fractions or the heparinoid. The inhibitory action of heparin (fractions) appeared to be the result of the formation of a complex between heparin and thrombin that alters the specificity of thrombin towards high molecular weight substrates. The inhibition of these thrombin-dependent feedback reactions in blood coagulation might be of importance in the mechanisms for the dissociation between the antithrombotic and hemorrhagic properties of low molecular weight heparins. PMID- 3086195 TI - [Effect of sulfamonomethoxine and ormetoprim on leucocytozoon infection in chickens]. AB - The preventive effect of sulfamonomethoxine (Smm) and ormetoprim (Omp) medicated in combination against leucocytozoon infection in chickens was tested in field trials. In trial 1, medication was given continuously throughout the experimental period. In trial 2, medication was given for seven days and no medication was given for the next seven days; then this schedule for the medication was repeated throughout the experimental period. In trial 1, almost complete prevention was obtained when Smm and Omp were added to the feed at the level of 12 ppm and 14 ppm, respectively, or at the level of 15 ppm and 5 ppm, respectively. Only a partial effect was obtained, however, when these drugs were used at the level of 9 ppm and 3 ppm, respectively. In trial 2, a nearly complete effect was obtained when Smm and Omp were added to the feed at the level of 18 ppm and 6 ppm respectively, but we found no effect when these drugs were used at the level of 15 ppm and 5 ppm, respectively. There were no significant differences among the groups as to the weight gain. PMID- 3086196 TI - [Ultrastructural studies of the conjunctival surface following long-term treatment with timolol]. PMID- 3086197 TI - [Prenatal ophthalmologic echography]. PMID- 3086198 TI - [Indwelling central venous catheters: indications, technics, complications]. PMID- 3086199 TI - A prepaid managed approach to long-term care. PMID- 3086200 TI - Lack of effect of thyrotropin-releasing hormone (TRH) on the peripheral plasma levels of pancreatic glucagon in man. AB - Based on the fact that human pancreas has thyrotropin-releasing hormone (TRH) immunoreactivity and bioactivity, we studied the effect of TRH on peripheral plasma levels of pancreatic glucagon (IRG) and insulin (IRI) in healthy subjects. During the infusion of 400 micrograms TRH for 120 min basal plasma IRI and IRG levels did not change significantly. In addition, intravenous infusion of 400 micrograms TRH did not affect the increments in the plasma IRG levels and the decrements in the blood glucose during insulin hypoglycemia. PMID- 3086201 TI - The anti-oestrogen tamoxifen does not interfere with the dopaminergic control of prolactin and TSH release in normogonadotrophic oligozoospermic man. AB - This study was designed to investigate the role of endogenous oestrogens in the dopaminergic regulation of prolactin and TSH release in 16 normogonadotrophic oligozoospermic men. Three months' administration of the oestrogen-receptor antagonist tamoxifen (10 mg twice daily), blocking oestrogen-receptors both in the CNS and peripherally, did not affect basal prolactin and TSH levels. Neither was the prolactin or TSH response to stimulation with the anti-dopaminergic agents metoclopramide (10 mg i.v.) (acting both in the CNS and peripherally) and domperidone (10 mg i.v.) (acting peripherally) affected by tamoxifen administration. The response of prolactin and TSH to metoclopramide proved to be no greater than to domperidone. It is concluded that: Endogenous oestrogens, in as far as receptor-mediated, do not affect basal or anti-dopaminergic stimulated release of both prolactin and TSH in normogonadotrophic oligozoospermic men. The anti-dopaminergic activity of metoclopramide in the release of prolactin and TSH is likely for the greater part peripheral. PMID- 3086202 TI - Potentiating effect of glibenclamide on the occurrence of alloxan diabetes in rats. PMID- 3086203 TI - Controlled trial of vasopressin plus nitroglycerin vs. vasopressin alone in the treatment of bleeding esophageal varices. AB - Thirty-nine patients admitted during a 16-month period for acute bleeding from varices confirmed by emergency endoscopy were randomized to receive either continuous intravenous infusions of vasopressin alone (0.66 units per min) (Group I: 19 patients) or vasopressin plus sublingual nitroglycerin (0.6 mg every 30 min for 6 hr) (Group II: 20 patients). The two groups of patients were similar in the type and severity of their cirrhosis. Bleeding was controlled initially in 47% (9/19) of the patients in Group I and 55% (11/20) of the patients in Group II after 6 hr of infusion (not statistically significant). Complete control of bleeding during 24 hr of infusion was achieved in only 4 of 19 patients in Group I (21%) but in 9 of 20 in Group II (45%). This difference is not statistically significant. The total number of patients with complications during infusions were significantly different statistically in the vasopressin and vasopressin nitroglycerin groups, respectively (17/19 vs. 7/20, p less than 0.001). Major complications requiring immediate cessation of infusions were observed in 6 of 19 of the patients in Group I (32%) and in 2 of 20 in Group II (10%) (p less than 0.05). Mortality (58% in Group I, 55% in Group II) and transfusion requirements were similar in the two groups. This study shows that the addition of sublingual nitroglycerin to intravenous vasopressin does not alter the efficacy of vasopressin alone in controlling hemorrhage from esophageal varices, but it does significantly reduce the complications. PMID- 3086204 TI - A randomized trial of vasopressin and vasopressin plus nitroglycerin in the control of acute variceal hemorrhage. AB - A randomized trial was undertaken to determine efficacy of nitroglycerin when added to a vasopressin infusion in both reducing the complication rate and giving improved control of acute variceal hemorrhage. Seventy-two bleeding episodes in 57 patients were included, with vasopressin being used on 34 occasions and vasopressin plus nitroglycerin on 38 occasions, for an infusion period of 12 hr. At the end of the 12-hr period, hemorrhage had been controlled significantly more frequently in those receiving combined therapy (26 of 38; 68%) than in those given vasopressin alone (15 of 34; 44%, p less than 0.05), although this difference was not statistically significant if those patients in whom therapy was discontinued due to drug complications were excluded from the analysis [hemorrhage controlled in the combined group (68%) and vasopressin alone (48%); chi 2 = 2.4, p greater than 0.05]. Major complications requiring cessation of therapy were significantly less common in those given nitroglycerin--one occasion compared to seven in those given vasopressin alone (p less than 0.02). Thus, the addition of nitroglycerin to a vasopressin infusion results in a lower rate of complications and is more effective in controlling variceal hemorrhage. PMID- 3086206 TI - Vasopressin and nitroglycerin in the treatment of bleeding varices: the bottom line. PMID- 3086205 TI - Sublobular distribution of transferases and hydrolases associated with glucuronide, sulfate and glutathione conjugation in human liver. AB - Activities of glucuronosyltransferase, sulfotransferase, glutathione S transferase, beta-glucuronidase and sulfatase were determined in microdissected samples of periportal and pericentral sublobular regions from four human livers obtained at immediate autopsy. New methods are presented for the microdetermination of sulfotransferase and sulfatase activities in microdissected samples weighing 0.1 to 4 micrograms dry weight using umbelliferone and 4 methylumbelliferone sulfate as substrates. The three transferases were distributed heterogeneously across the liver lobule. Glucuronosyltransferase and glutathione S-transferase were localized predominantly in pericentral regions. In contrast, sulfotransferase activity was greater in periportal than pericentral regions. Average activities for glucuronosyltransferase and sulfotransferase were 23, and 50 mumoles X gm dry wt-1 X hr-1, respectively, in periportal regions, and 34 and 38 mumoles X gm dry st-1 X hr-1, respectively, in pericentral regions. Activities of glutathione S-transferase were considerably higher than those of the other transferases and were 8.3 mmoles X gm dry wt-1 X hr-1 in periportal areas and 12.2 mmoles X gm dry wt-1 hr-1 in pericentral areas. The two hydrolases studied, beta-glucuronidase and sulfatase, were evenly distributed across the liver lobule. The presence of significant hydrolase and transferase activities in both zones of the liver lobule supports the idea that net production of both sulfate and glucuronide conjugates may be influenced by futile cycling of conjugation-deconjugation reactions in both zones of the liver. Based on enhanced formation of sulfate but not glucuronide conjugates in homogenates of human liver treated with inhibitors of the hydrolases, it is suggested that futile cycling is more pertinent to the regulation of sulfation than glucuronidation. PMID- 3086207 TI - The central issue of cholesterol gallstones. PMID- 3086208 TI - Immunohistochemistry of primary gastrointestinal lymphomas: a study of 76 cases. AB - A retrospective study of 76 primary gastrointestinal lymphomas utilizing an avidin: biotinylated horseradish peroxidase complex (ABC) technique demonstrated 22 B-cell lymphomas, including two associated with alpha-heavy chain disease. Seven cases were classified as true histiocytic lymphomas based on a positive reaction for one or more of three histiocytic enzyme markers utilized, predominantly alpha-1-antitrypsin and alpha-1-antichymotrypsin. However, in 20 cases, an intense admixture of reactive histiocytes was noted and these cells stained preferentially for the enzyme, lysozyme. Twenty cases, which stained for both kappa and lambda light chains and positively or negatively for albumin, could not be classified and 27 cases failed to stain with any of the antisera utilized. PMID- 3086209 TI - Ganglioside GM1 metabolism in living human fibroblasts with beta-galactosidase deficiency. AB - The uptake and catabolism of [3H-ceramide]-GM1 was followed in living fibroblasts from patient with different forms of beta-galactosidase deficiency. Gangliosides are identified according to the nomenclature of Svennerholm (1963). A total inability to metabolize the ingested substrate was found in infantile GM1 gangliosidosis whereas cells from an adult GM1-gangliosidosis variant showed a slower rate of degradation, compared with controls. Morquio B fibroblasts had a comparable catabolism of GM1 as controls. Fibroblasts from different types of galactosialidosis, a recessive disease associated with a coexistent beta galactosidase/neuraminidase deficiency all showed degradation of ingested GM1. In view of the molecular defect in this disease, this catabolism must be due to the 10-20% of monomeric beta-galactosidase molecules present in the lysosomes. Unexpectedly, in these cells an impaired metabolism of GM3 was found. The same finding was observed when cells with an isolated neuraminidase deficiency (mucolipidosis I) were loaded with GM1. A hypothesis is presented to explain these results. PMID- 3086211 TI - Evaluation of four methods for estimating breath-by-breath exchange of O2 and CO2. PMID- 3086210 TI - Adaptation-like response to the chemical induction of sister chromatid exchanges in human lymphocytes. AB - Experiments have been performed to determine whether human lymphocytes in primary cultures can show an "adaptive" response to the induction of cellular lesions (manifested as a production of sister chromatid exchanges, SCEs) as previously found in bacteria and established human and mammalian cell lines. Human lymphocytes were pretreated with various subtoxic concentrations (5-50 ng/ml) of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) once every 6h for 72 h, and subsequently challenged by a high dose (4 micrograms/ml) of MNNG. The lymphocytes in MNNG-challenged cultures had the lowest frequency of SCEs when pretreated with 10 ng/ml MNNG. Further cross-resistance study revealed that repeated pretreatments of lymphocytes with 10 ng/ml MNNG for 72 h can render the cells resistant to the induction of SCEs by the following challenge with a high dose of MNNG, but not of mitomycin C or ethyl nitrosourea. The data also suggest variations in the degree of the adaptation-like response among individuals. PMID- 3086212 TI - [Pathogenicity of Listeria]. AB - 20 different Listeria strains which hitherto have been all classed with the same serovar 3 of L. monocytogenes because of common surface markers, differ markedly in respect to their pathogenic capacities. Some strains are virulent, because they are able to multiply within a normal, adult mouse. Others show only weak virulence, since they survive within the host for several days. Multiplication, however, does not occur. Still other strains are rapidly eliminated and thus avirulent. These characteristics are still more pronounced in the compromised host. The avirulent strains are even not able to multiply in mice deprived of macrophage function, in T-lymphocyte-deficient mice or in newborn mice. These avirulent strains have to be classified into the new species of L. innuocua because of biochemical markers, whereby the absence of hemolysin production is crucial. Whereas priming of protective immunity is only possible by strains of high and intermediate virulence of L. monocytogenes, boosting of pre-existing immunity could also be achieved by the avirulent strain of L. innocua. PMID- 3086213 TI - A study on class II antigens involved in the T cell proliferative responses to PPD using cross-reacting monoclonal antibodies in human and murine system. AB - Two monoclonal antibodies (MoAb) 1E4 and ISCR3, which detect class II antigens across species barriers, were studied for their inhibitory effects on human and murine T cell proliferative responses to purified protein derivative of tuberculin (PPD). The 1E4 detected at least a polymorphic determinant on I-A molecules from mice carrying the H-2b haplotype, and the ISCR3 detected the Ia.7 determinant on I-E molecules. Nevertheless, both 1E4 and ISCR3 recognized monomorphic determinants on HLA-DR antigens (human I-E equivalent molecules), but not on HLA-DQ antigens (human I-A equivalent molecules). It was demonstrated that 1E4 significantly inhibited PPD-specific responses of T cells from Ib-bearing mice. In contrast, ISCR3 showed marginal effects on the responses of mice bearing Ia.7. However, in the human system both 1E4 and ISCR3 reduced proliferative responses to PPD. These results suggest that a functional difference exists between humans and mice in the I subregion products involved in the T cell proliferative responses to PPD. PMID- 3086214 TI - Macrophage Ia expression in athymic nude versus neonatally thymectomized mice. AB - The requirement of the thymus for the production of Ia-inducing lymphokine was studied in athymic nude, neonatally thymectomized (NTx), and sham-operated (Sham) mice. The peritoneal macrophages from NTx mice immunized with viable Listeria monocytogenes 14 days previously contained as high a proportion of Ia-bearing macrophages as those from Sham mice, while those from athymic nude mice contained only a small proportion. Intraperitoneal injection of a culture supernatant derived from immune spleen cells of NTx mice induced Ia-rich exudates in recipient normal mice just as well as did a corresponding supernatant from cells of Sham mice, but that from cells of athymic nude did not. The production of Ia inducing lymphokine in culture supernatants of immune spleen cells from both NTx and Sham mice was abolished by pretreatment of cells with anti-Thy-1.2 antibody plus complement. These results suggest that a T cell subset responsible for the production of Ia-inducing lymphokine requires the presence of the thymus for just a short period in the ontogenic development. PMID- 3086215 TI - Calcium ionophore A 23 187 in the presence of phorbol ester PMA: a potent inducer of interleukin 2 and interferon-gamma synthesis by human blood cells. AB - Cultures of human blood mononuclear cells incubated with the calcium ionophore A 23 187 in the presence of the tumor promoter phorbol 12-myristate-13-acetate (PMA) produced 5-10 times more of the lymphokines interleukin 2 (IL 2) and interferon-gamma (IFN-gamma) than cultures which were stimulated with other combinations of inducing agents and PMA. Especially at low protein concentrations, the amount of ionophore which is necessary to induce maximal quantities of both lymphokines was determined by the protein content of the culture medium. The synthesis of the two lymphokines was inhibited by low doses of Mn++ which competes with Ca++ for binding to the ionophore. This suggests the importance of Ca++ in the induction process. The synthesis rates of IL 2 were maximal 10-12 h, and those of IFN-gamma 20-40 h after induction. Maximal titers of IL 2 were detected 48 h after the addition of A 23187 and PMA to the cultures, and the highest IFN-gamma levels 12-24 h later. PMID- 3086216 TI - Effects of cyclosporin A on functions of specific murine T cell clones: inhibition of proliferation, lymphokine secretion and cytotoxicity. AB - Allospecific T lymphocyte clones with different functions were generated from spleen cells of C 57/Bl6 mice following sensitization in vitro by a one-way mixed lymphocyte culture (MLC) with irradiated DBA/2 spleen cells. The clones were propagated in vitro in the presence of interleukin 2 (IL 2) and restimulation with stimulator cells. In these clones Cyclosporin A (CSA) was tested for its suppressive effect on different T lymphocyte functions. The antigen-dependent proliferation of a helper clone (HTL) was totally inhibited by 50 ng/ml CSA. Proliferation induced by simultaneous administration of antigen and IL 2 was partially suppressed in all helper and cytotoxic clones (CTL). The IL 2-driven proliferation in the absence of antigen was also suppressed between 25-70% by the immunosuppressive drug. Secretion of macrophage activating factor (MAF) and interferon (IFN) by HTL and CTL in response to antigen or mitogen was reduced dose dependently by CSA. Concentrations of 50 ng/ml CSA diminished lymphokine secretion to approximately 10% of controls, also when excess IL 2 was present. Cytotoxicity, previously described to be insensitive to the drug, could be suppressed by 50 ng/ml CSA to a various extent, from 40-70%, in different cytotoxic clones when the effector cells were preincubated with CSA for 1 h or more. Conclusively, the data suggest that CSA interferes generally with the activation of T lymphocyte clones. PMID- 3086217 TI - Interleukin 2 induces both, growth and maturation of lectin reactive Lyt-2+ but not Lyt-2-precursor cells and regulates the cytolytic potential of effector cells. AB - This study investigated the requirements for lymphokines derived by recombinant (rec.) DNA technology for the induction of growth and maturation in highly purified lectin reactive T cell subsets. Nylon purified C57BL/6 lymph node T cells were treated with monoclonal anti-Lyt-2.2 or anti-L3T4 antibodies and fluorescence labeled (FITC) anti-immunoglobulin antibodies and were positively selected into Lyt-2+ (L3T4-) and Lyt-2- (L3T4+) lymphocyte subsets using a fluorescence-activated cell sorter. Sorted T lymphocytes, which were devoid of accessory cells were incubated either in bulk culture (2 X 10(2) - 3 X 10(4) cells/microculture) or under limiting dilution conditions (2.5-1,000 cells/well) with lectin (Concanavalin A, Leukoagglutinin) and rec. human Interleukin 2 (rec. hIL-2) and/or rec. mouse Interferon gamma (rec. mIFN-gamma). The data show that Lyt-2+ lymphocytes respond to lectin and rec. hIL-2 with growth and development of cytolytic activity in the absence of other exogenous factor(s) or accessory cells. The presence of monoclonal antibodies to the Interleukin 2 receptor during the sensitization phase ablated the induction of Con A reactive precursor cells of cytolytic lymphocytes (CTL-P) by either rec. hIL-2 or conventional IL-2 containing lymphokine sources, indicating the essential role of IL-2 during activation of Lyt-2+ T lymphocytes. In contrast, Lyt-2- lymphocytes could not be induced by lectin and rec. hIL-2 alone for proliferation and always required the presence of accessory cells for significant growth. Exogenous rec. m IFN gamma was unable to induce growth and cytolytic activity in Con A reactive Lyt-2+ cells and did not significantly effect their response to rec. hIL-2. Limiting dilution experiments revealed that 10-16% of the Lyt-2+ lymphocytes responded to Con A and rec. hIL-2 with growth (GTL-P). The frequencies of CTL-P, determined under similar conditions, were always lower compared to GTL-P. However the results suggest that the differences observed between both precursor populations is due to differential sensitivity of the detection system rather than to the recruitment of distinct T cell subsets. Furthermore, it was shown that at least 50% of lectin reactive CTL-P were induced by rec. hIL-2 to secrete IFN-gamma under optimal conditions. The finding that some of the conventional lymphokine sources were superior to rec. hIL-2 in the induction of growth and cytolytic activity suggests the existence of mediators distinct from IL-2 that regulate the expansion of CTL-P.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3086218 TI - Age-dependent variations of intralysosomal enzyme release from human PMN leukocytes under various stimuli. AB - The intralysosomal beta glucuronidase and elastase release from polymorphonuclear leukocytes (PMNL) of young and aged male subjects were determined after 60-min incubation with 10 micrograms/ml Cytochalasin B (CB), 10(-6) M of Ca ionophore A 23187 and various concentrations of human low density lipoprotein (LDL). The beta glucoronidase secretion was triggered by both A 23187 and LDL; however, no significant differences were found between the enzyme release from PMNLs of young and aged subjects. In contrast, a marked elastase release was triggered in the young group only by LDL, whereas in the aged group, all of the applied drugs induced a significant elastase release. LDL caused the most dramatic enzyme release from PMNLs of aged males. It was concluded that the release of PMNL elastase after LDL incorporation as well as by CB and Ca ionophore stimulation may be an age-related process. PMID- 3086219 TI - The role of phosphate groups in the interaction of human C-reactive protein with galactan polysaccharides. AB - Human C-reactive protein (CRP) shows binding specificities for phosphate monoesters, polycations and for several other biological macromolecules lacking these ligands. We report here that the formerly observed interaction of CRP with snail galactans, as exemplified by Helix pomatia galactan, is not due to a lectin like carbohydrate-binding reactivity, but, instead that CRP obviously binds to phosphate groups that are minor constituents of these polysaccharides. Structural analysis of the galactan revealed that the phosphate groups are attached by a, as yet unidentified, linkage group to the carbohydrate backbone. Thus, the anti galactan reactivity of CRP can be attributed to the protein's classical anti phosphate/anti-phosphorylcholine specificity. PMID- 3086220 TI - Cells bearing class II MHC antigens in the human placenta and amniochorion. AB - Immunohistological techniques have been used to study the stromal cells of the human placenta in both the chorionic villous mesenchyme and the connective tissue underlying the amnion. Throughout gestation many of these cells express an antigen (3C10) that is found on mononuclear phagocytes but not on dendritic cells or epidermal Langerhans cells. In the first and second trimesters the placental cells also react with a monoclonal antibody (NA1/34) to the human thymocyte antigen (CD1), a lymphocyte differentiation antigen expressed by cortical thymocytes and Langerhans cells; expression of this antigen diminishes as gestation advances. In contrast, an antibody to a different epitope of CD1 (OKT6) does not bind. Class II MHC antigens are not present in the first trimester but are acquired by increasing numbers of placental macrophages from the second trimester onwards. It is possible that the placenta has significant immune functions and that, by term, placental macrophages may be capable of antigen presentation. PMID- 3086221 TI - The cellular pathway of antigen presentation: biochemical and functional analysis of antigen processing in dendritic cells and macrophages. AB - The response of primed T cells to keyhole limpet haemocyanin (KLH) was used to compare the characteristics of antigen presentation by lymphoid dendritic cells, splenic and peritoneal macrophages. In a similar manner to macrophages, purified dendritic cells could be pulsed with antigen and subsequently fixed by brief glutaraldehyde fixation and still retain antigen presenting activity. Also, as previously reported for macrophages, presentation could be inhibited by chloroquine. These functional experiments suggested that the pathway of antigen presentation in dendritic cells and macrophages was similar or identical. However, biochemical studies, using radiolabelled antigen, showed that dendritic cells do not significantly degrade large proteins such as KLH to TCA-soluble form, but partially hydrolyse them to smaller peptide fragments. The significance of these results in terms of a model of the cellular pathways of antigen presentation is discussed. PMID- 3086222 TI - Bile immunoglobulin of the duck (Anas platyrhynchos). I. Preliminary characterization and ontogeny. AB - Immunoglobulin (Ig) of a single class was found in duck (Anas platyrhynchos) bile. Its molecular weight was 890,000; serum IgM was 800,000. Heavy chains were 75,000 for bile Ig, 86,000 for IgM, 67,000 for 7.8S IgG and 37,000 for 5.7S IgG. Antigenic comparison showed that bile Ig resembled IgM but carried additional determinants. The ontogeny of bile Ig was distinct from that of serum IgM and IgG. Thus, duck bile Ig appears to be an IgM-like molecule secreted independently of serum Ig. PMID- 3086223 TI - How many class II immune response genes? A reappraisal of the evidence. PMID- 3086224 TI - A combined detection & drug susceptibility testing of Mycobacterium tuberculosis in smear positive sputum samples using biphasic vial radiometric method. PMID- 3086226 TI - [5th joint annual meeting. Austrian and German Societies for Artificial Nutrition. Salzburg, 13-15 March 1986. Abstracts]. PMID- 3086225 TI - Development of antitumor activity in LPS-stimulated mouse granuloma macrophages. Regulation by eicosanoids. AB - Macrophage-mediated antitumor activity is believed to be regulated by E-type prostaglandins released by target cells or even by macrophages themselves. In these studies we showed that a subcutaneous injection of polyacrylamide beads (Biogel P100), induced in mice, a population of immature macrophages which became fully cytostatic to syngeneic P815 mastocytoma when pulsed in vitro with lipopolysaccharide (LPS). Blockade of prostaglandin synthesis by indomethacin prevented LPS effect and led to a substantial resumption of target growth. Addition of PGE2 did not reverse the indomethacin effect but inhibited macrophage mediated cytostatic activity. These findings suggest that acquisition of cytostatic properties by macrophages is, at a certain stage of their maturation, under the control of both PGE2 and another endogenously produced eicosanoid. PMID- 3086227 TI - [Indirect calorimetry in mechanically ventilated children. 3. Clinical use of a new measurement procedure]. AB - After the new device for measurement of oxygen uptake (VO2) and carbon dioxide elimination (VCO2) was tested in a pneumatic lung model, we investigated its clinical practicability. First the level of VO2 and VCO2 in the early postoperative phase was determined. Secondly we examined alterations in gasexchange caused by various intensive care activities. Whereby main concern was the change from mechanical ventilation to spontaneous CPAP-breathing. Ten children undergoing cardiac surgery (age: 10 days to 10 years) were included in the study. Three children were primarily investigated on the CPAP-system. Data from another six were collected under controlled ventilation as well as under spontaneous CPAP-breathing. One child had to be ventilated for a longer time (greater than 24 h). The change from mechanical ventilation to spontaneous breathing was accompanied with a temporary increase of VO2 and VCO2. As expected, all stressful factors like tracheal suction, pain or anxiety increased these two variables. Also some drugs showed remarkable changes. While marked increases under Normastigmine, Naloxone, and Dopamine could be observed, gas exchange was decreased under Morphine. However, heart rate showed no good correlation with VO2. We conclude that the developed prototype is a reliable device for measuring VO2 and VCO2. Our results suggest that spontaneous CPAP-breathing is not always accompanied with increased gas exchange. If there is an increased gas exchange, it may refer to transient changes during the adaption phase. Therefore, a continuous monitoring of VO2 and VCO2 over a longer period of time is necessary. Consequently the first phase after changing ventilatory support has to be viewed carefully. The heart rate in children, undergone cardiac surgery, is not a good predictor for determination of VO2 and thus for energy expenditure. This device allows to quantify accurately oxygen consumption and carbon dioxide elimination in ventilated children. Furthermore, alterations in metabolism and cardiopulmonary variables caused by intensive care and therapeutic interventions can be examined continuously. It seems to be a valuable tool for metabolic and cardiopulmonary monitoring in critically ill children. PMID- 3086228 TI - [Effect of aggressive tumor therapy on nutrient utilization and nutritional status]. AB - The nutritional consequences of oncologic surgery, cytostatic treatment, and of radiotherapy are reviewed with special respect to gastrointestinal function as well as nutrient assimilation and utilization. The different types of nutritional intervention, which may be necessary to overcome the treatment-induced malnutrition are discussed. PMID- 3086229 TI - T-cell immunity in murine malaria: adoptive transfer of resistance to Plasmodium chabaudi adami in nude mice with splenic T cells. AB - Acute infections caused by the murine malarial parasite Plasmodium chabaudi adami are resolved by antibody-independent mechanisms of immunity. The fact that athymic nude mice developed high-grade unrelenting malaria and died when infected with this parasite suggested a significant role for T lymphocytes. Using adoptive transfer techniques, we demonstrated that spleen cells from either nonimmune or immune donor BALB/c mice eventually suppressed P. chabaudi adami infections in histocompatible recipient nude mice in a dose-dependent manner. Infections in recipients of "immune" spleen cells were less severe, demonstrating a depressed peak parasitemia and a shortened duration of patent infection, than was observed in recipients of normal spleen cells. Also, when sufficient numbers of immune spleen cells were transferred, the second wave of parasitemia (characteristic of this infection in nonimmune mice) failed to occur. T lymphocytes mediated protection in recipient mice, since T-cell-enriched, but not B-cell-enriched, spleen cell fractions suppressed P. chabaudi adami infections in nude mice. Protection was best achieved with T cells that bore the L3T4 phenotype. Patent parasitemias developed in all recipient mice, suggesting that the grafted cells did not limit parasite growth directly but achieved this end by activating other as yet unidentified inhibiting cell systems. PMID- 3086230 TI - Effects of human serum on bacterial competition with neutrophils for molecular oxygen. AB - A dialyzable factor(s) in human serum is known to stimulate gonococcal oxygen consumption. Its effect on other human pathogens was investigated. A 10% serum solution increased peak O2 consumption for Escherichia coli and Staphylococcus aureus to 157% (P less than 0.05) and 199% (P less than 0.02), respectively, of their O2 consumption when suspended in Hanks balanced salt solution, compared with a 356% increase for Neisseria gonorrhoeae with serum. Dialyzed serum lacked stimulatory capacity. Bacteria, serum, and neutrophils are often incubated to evaluate neutrophil bactericidal activity. Samples of 10(8) N. gonorrhoeae, S. aureus, and E. coli turned resazurin colorless (anaerobic conditions, Eh less than -42 mV) after 7.4, 13.3, and 15.1 min, respectively. Because neutrophil formation of reactive oxygen intermediates requires ambient O2, the effect of live bacteria and serum on this process was explored. After 5 min of incubation of 10(8) N. gonorrhoeae or S. aureus in 10% normal or dialyzed serum, 10(5) neutrophils were added. Phorbol myristate acetate was then added to assure neutrophil stimulation, and luminol-dependent luminescence was measured. N. gonorrhoeae and S. aureus incubation in normal serum decreased peak LDL 91.7 and 88.6%, respectively, relative to incubation in dialyzed serum. A sample of 10(8) E. coli totally eliminated LDL. A sample of 10(8) E. coli incubated in Hanks balanced salt solution for 5 min also eliminated phorbol myristate acetate induced neutrophil H2O2 production. LDL inhibition increased in proportion to bacterial concentration and time of incubation and was prevented by inclusion of KCN. Increasing the concentration of neutrophils to 10(8) (1:1 particle-to-cell ratio) only partially reversed LDL inhibition. Re-aeration of the system allowed brief LDL which persisted only if KCN was added. Addition of KCN after bacterial incubation also permitted LDL, arguing against depletion of other factors from the media or accumulation of bacterially derived inhibitory substances. A dynamic competition for O2 occurs between bacteria and neutrophils. Serum stimulation of bacterial O2 utilization may contribute to virulence by increasing bacterial capacity to inhibit neutrophil function. PMID- 3086233 TI - Antischistosomal effect of cyclosporin A: cure and prevention of mouse and rat schistosomiasis mansoni. AB - C57BL/6 mice infected with Schistosoma mansoni at day 0 and injected with cyclosporin A (CyA) either daily or from day -1 to day 3 were protected against schistosomiasis mansoni as indicated by a decrease in the number of worms recovered from the liver 45 days after infection. CyA treatment also protected rats and strains of mice with known immunity defects (nu/nu, P/N, CBA/N). Protection was evident against both primary and secondary infection in mice infected at day 0, reinfected at day 42, and treated daily with CyA either during the course of the experiment or only from day -1 to day 3, as indicated by the worm burden at day 67. In such an experiment of infection and reinfection, the immature worms were shown to be the target of CyA. Administration of the drug 27, 45, 62, or 100 days before infection confirmed the long-term protective effect of CyA. This drug did not evoke the killing of adult worms in vivo. These data confirm and define the curative and preventive effect of CyA against schistosomiasis mansoni. PMID- 3086231 TI - Serum amyloid P-component-induced enhancement of macrophage listericidal activity. AB - Purified serum amyloid P component (SAP), the major acute-phase reactant of mice, augmented the in vitro listericidal activity of inflammatory (elicited) macrophages, bone marrow-derived monocytes, and macrophages from a subcutaneous site of inflammation. Monocytes and macrophages from C57BL/B6 mice, which are relatively resistant to Listeria monocytogenes, exhibited a significantly greater enhanced killing capacity for listeria than macrophages from listeria-susceptible A/J mice. SAP did not alter the extent of phagocytosis by macrophages of opsonized L. monocytogenes, nor was SAP opsonic for listeria. Mannose-derived simple sugars inhibited the binding of SAP to macrophages and consequently prevented the enhanced SAP-dependent listericidal activity. Macrophages from lipopolysaccharide-hyporesponsive mice also had increased microbicidal activity following incubation with SAP. SAP activated macrophages independently of lymphokine. Therefore, SAP may serve as a mediator of the heightened nonspecific host defense response that is associated with the acute phase of the systemic inflammatory response. PMID- 3086232 TI - Modulation of complement fixation and the phlogistic capacity of group A, B, and D streptococci by human lysozyme acting on their cell walls. AB - Streptococci and streptococcal cell wall fragments induce arthritis in rats, with the severity and duration depending on the capacity of the cells or cell fragments to resist degradation by tissue enzymes. Their phlogogenic effects are apparently related to their ability to activate the alternate complement pathway (ACP). The in vitro activation of the ACP by lysozyme-treated cells and cell walls of group A, B, and D streptococci suggests that both rat and human lysozyme can modulate this activity, i.e., increasing it, decreasing it, or doing both in that order. The effects of the lysozymes also correlated with the degree to which they can unmask the aminosugar-reducing groups detectable in a given amount of cell wall, which suggests that partial depolymerization of the cell wall is critical for ACP activation. The effects of mutanolysin and C phage lysin on ACP activation were found to be correlated with their action on streptococcal cell walls. Neuraminidase had relatively little effect on ACP activation by most streptococcal strains tested. We conclude that the participation of tissue enzymes, including but not necessarily limited to lysozyme, is an important determinant for the clinical arthritis induced by group A, B, or D streptococci. Experimental arthritis induced in rats with whole (or disrupted) streptococci may depend both on the capacities of the cell walls to activate the ACP and on the capacities of the host tissue enzymes to modulate this activation. Great severity and long durations of the disease were determined by the capacity of the enzymes to degrade cell wall antigens to a degree sufficient to ensure efficient activation of the ACP without completely degrading the material so that it no longer activates complement. In this model, the limited resistance of group B peptidoglycan to lysozyme was a critical pathogenic factor. PMID- 3086234 TI - Natural and recombinant interferons inhibit epithelial cell invasion by Shigella spp. AB - The effect of natural and recombinant interferons (IFNs) on the abilities of Shigella flexneri, S. sonnei, and Salmonella typhimurium to invade different human and murine cells was examined. Pretreatment of cell monolayers with natural and recombinant IFNs reduced the number of Shigella-infected cells in a dose dependent manner. Establishment of an anti-invasive cellular state was time dependent, requiring 10 h for 50% inhibition of bacterial invasion. The inhibitory effect of IFN was species specific, with human or murine IFN effective against homologous but not heterologous cells. Gamma IFN was slightly more potent than alpha IFN at inhibiting bacterial invasion. Inhibition of Shigella invasion was dependent on the challenge dose of bacteria. Little inhibition of invasion was seen when cells were pretreated with low concentrations of IFN and challenged with high multiplicities of infection of Shigella sp. In contrast to Shigella invasion, the maximum inhibitory effect of IFN on Salmonella invasion of cells was observed at low levels (5 to 50 U) of IFN. These results suggest that Shigella and Salmonella invasions occur at unique sites on eucaryotic cells or by different penetration mechanisms. More importantly, these data suggest that IFN may play a significant role in host defense against Shigella and Salmonella infections. PMID- 3086235 TI - Lung defenses against Pseudomonas aeruginosa in C5-deficient mice with different genetic backgrounds. AB - Lung defenses against Pseudomonas aeruginosa were investigated in C5-deficient strains of mice with different genetic backgrounds. We studied pulmonary clearance and cell responses after aerosol exposure to P. aeruginosa in C5 deficient B10.D2/oSnJ and DBA/2J mice and their closest C5-sufficient counterparts, B10.D2/nSnJ and DBA/1J mice. Different patterns of lung clearance and pulmonary cell responses were found for the two C5-deficient strains. C5 deficient B10.D2/oSnJ mice showed defective lung clearance of P. aeruginosa 4 h after challenge compared with C5-sufficient B10.D2/nSnJ animals. This finding was associated with a decreased number of polymorphonuclear leukocytes recruited into the airways during the same time. Interestingly, C5-deficient DBA/2J mice recruited higher numbers of polymorphonuclear leukocytes than did C5-sufficient DBA/1J mice by 4 h after aerosolization. Nevertheless, lung clearance of P. aeruginosa in DBA/2J mice was not as effective as in C5-sufficient DBA/1J mice, suggesting that other functions of C5 besides chemotaxism could be involved. Lung clearance of P. aeruginosa was also investigated in C5-deficient and -sufficient hybrids sharing the same genetic background (DBA/2J X B10.D2). The results suggested that murine lung clearance of P. aeruginosa is markedly affected by lack of C5 in a specific genetic background (B10.D2). PMID- 3086236 TI - Epidemiological aspects of acute viral hepatitis in Portugal. AB - Epidemiological aspects of 400 consecutive in-patients with acute viral hepatitis, aged one to 81 years, were studied: 180 patients were less than 15 years old (mean age 6.9 years) and 220 were older (mean age 33.8 years). Serum hepatitis markers were detected by RIA. Hepatitis A (HA) was diagnosed in 188 patients (47.0%), ages ranging from one to 34 years (mean age 8.5 years), hepatitis B (HB) in 163 patients (40.8%), ages ranging from two to 72 years (mean age 32.7 years) and non-A, non-B hepatitis (NANBH) in 41 patients (10.2%), ages ranging from two to 81 years (mean age 35.4 years). Two patients had simultaneous HA and HB, and in six patients the etiology was not classified. In patients less than 15 years old, HA was the commonest type (91.1%), other etiologies having a low frequency; in the age group over 15 years, HB represented the most frequent type (70.0%), followed by NANBH (16.8%) and HA (10.9%). The probable source of infection was unknown in most of the cases (51%). With regard to HA, secondary contact was frequently reported and small outbreaks were registered. Parenteral exposure was the main probable source of HB and NANBH virus infections, the transmission frequently being iatrogenic. Drug abuse was a rare source of infection. PMID- 3086237 TI - Epidemiology and risk calculation of hepatitis-B as an occupational disease in the Austrian health service. AB - The present investigation of occupation-related cases of hepatitis in the statistics of occupational diseases attempted to quantify the specific risk of this infectious disease for all occupations within the health service. The absolute number of occupation-related cases of hepatitis B increased fourfold over the last two decades, while at the same time the number of health service employees only doubled. In comparison with the Austrian population, the hepatitis risk is about 11 times higher for the health service employees. Especially laboratory personnel, doctors and support service personnel are exposed to these increased risks. The relative risks according to age, sex and type of occupation were also investigated and a comparison was made with the findings of other investigations in Austrian and international specialized literature. First information is also given about the findings of the screening on immunity against HBs-antigen, anti-HBs and anti-HBc in the professional group of health service employees. The calculations, and also experience in other countries, show the need for the introduction of an active protective immunization against hepatitis B for all health service employees. The prophylaxis against hepatitis that was begun in Austria on January 1st, 1983, is the first extensive vaccination programme against this liver disease, that on the basis of research done by a social security institute, has been implemented free of charge by this institute for a professional category. PMID- 3086238 TI - Immunochemical characterization of saline-extracted antigens of Mycobacterium tuberculosis H37Ra. AB - The saline extract (SE) of Mycobacterium tuberculosis H37Ra yielded four major fractions on Sephadex G-100, with average molecular weights of 48,000 (fraction I, F I) 32,000 (fraction II, F II), 15,000 (fraction III, F III) and 5,000 (fraction IV, F IV). FI and FII gave single bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis, showed complete immunological cross reactivity with each other and were more potent in reacting with antibodies in patients' (tuberculosis) sera than sonicate, SE, purified protein derivative, F III and F IV when tested in a competition enzyme-linked immunosorbent assay. PMID- 3086239 TI - Separation, phenotyping and limiting dilution analysis of T-lymphocytes infiltrating human solid tumors. AB - Tumor-infiltrating lymphocytes (TIL) were obtained by a combination of mechanical release and enzymatic disaggregation from 35 human solid tumors. The number of lymphocytes in TIL-enriched suspensions varied from 1 X 10(4) to 7.6 X 10(6) per wet gram of tumor. The TIL preparations separated by differential centrifugation on Ficoll-Hypaque gradients contained 10-95% of T11+ cells (mean 50%), and tumor cells accounted for the other major cellular component. Macrophages, NK cells, B cells and granulocytes were infrequently seen. Morphologically, TIL-T were small non-activated cells. They expressed the T11 and T3 antigens but not the receptor for IL-2 (IL-2R) or HLA-DR antigens as determined by double immunofluorescence staining. Rare T11+/IL-2R+ cells were recovered only from colon and lung carcinomas. The mean T4/T8 ratio in 12 TIL preparations was 1.1 +/- 0.8. Immunohistology with monoclonal antibodies (MAbs) performed in 31/35 tumors confirmed that the T11+ cells infiltrating solid tumors rarely expressed the IL 2R and that the cell content of suspensions enriched in TIL was comparable to that determined in situ. The recovered TIL were cloned in a microculture system that permits proliferation of nearly all normal peripheral blood T lymphocytes (PBL-T). Under these culture conditions, frequencies of the proliferating T lymphocyte precursors (PTL-P) were depressed in both the TIL preparations (less than 0.01 to 0.39) and patients' PBL-T (0.05 to 0.5). These low frequencies of PTL-P were seen in patients with all tumor types, both primary and metastatic. PMID- 3086240 TI - Ca2+ and calmodulin are involved in the processes conferring stability to DNA in proliferating neoplastic cells. AB - We have examined, in proliferating neoplastic cells, the effect on DNA of EGTA (a chelator of Ca2+) and W7 (an inhibitor of calmodulin). The treatment results in release of single-stranded DNA fragments (2-10 kb) from pre-labelled HMW DNA. When DNA from synchronized neoplastic cells in S phase is examined, almost all pre-labelled DNA appears as short fragments. However, fragmentation does not occur in growth-arrested cells or in normal cells. Furthermore, fragmentation can be prevented by incubating cells in excessive amounts of Ca2+. Hence Ca2+ and the Ca2+-binding protein calmodulin are involved in the processes conferring stability to DNA in proliferating neoplastic cells. PMID- 3086241 TI - Antacid does not reduce the bioavailability of oral contraceptive steroids in women. AB - The bioavailability of contraceptive steroids was studied in 12 women who were given an antacid and a contraceptive pill simultaneously. They were given a single pill containing ethinyl estradiol (EE2) 30 micrograms in combination with either norethisterone (NET) acetate 1 mg (n = 6), or levonorgestrel (LNg) 150 micrograms, (n = 6). Blood samples were collected up to 24 hours. Four weeks later the same pill was administered along with a single tablet of antacid (magnesium trisilicate 0.5 g and dried aluminum hydroxide 0.25 g) and blood samples were collected as before. Serum levels of NET, LNg and EE2 were measured by radioimmunoassay. No effect of antacid administration on bioavailability of any contraceptive steroid was observed as judged by peak levels and areas under concentration-time curve (AUC). Incidentally, significantly higher serum concentrations of EE2 were observed when it was administered in combination with NET than with LNg. The possible reasons for this finding are discussed. PMID- 3086242 TI - Dose finding of tocainide in the treatment of tinnitus. AB - A dose finding study was performed for the use of oral tocainide in the treatment of tinnitus. In a single-blind study, increasing doses of tocainide hydrochloride ranging from 0 to 1800 mg and back to 0 mg were administered to 19 patients. Each dose was given for 4 days and the effects as well as the serum concentrations were recorded on the 4th day. In 8 patients the symptoms regressed to a non troublesome level. In most instances this effect was seen at doses of 900 and 1800 mg, respectively. Side effects were frequent. The most important side effect, which was an absolute indication for termination of the study, was an exanthema that developed in 7 of the patients (37%). Taking into account all side effects observed, it was concluded that no justification exists for doses over 900 mg daily for the treatment of tinnitus. However, in comparison with lidocaine, which can only be given intravenously, the therapeutic score of tocainide is low and in fact tocainide is no satisfactory alternative to lidocaine. PMID- 3086243 TI - The effect of alpha-difluoromethylornithine on natural killer cell and tumoricidal macrophage induction by interferon in vivo. AB - The objective of the present investigation was to evaluate the effect of DFMO (DL alpha-difluoromethylornithine HCl H2O) administration on tumoricidal effector cell generation by IFN or IFN inducers in vivo. DFMO administration reduces both splenic leukocyte and peritoneal macrophage polyamine levels. In tumor bearing (B16 melanoma) mice, DFMO administration did not impair splenic natural killer (NK) cell augmentation, assessed against NK sensitive YAC-1 target cells, by IFN alpha/beta or the IFN inducers tilorone and polyriboinosinic: polyribocytidilic acid (poly I:C). Tumoricidal macrophage activation by IFN alpha/beta was similarly uninhibited by DFMO. However, only tumoricidal macrophage not NK cell activity was observed which could kill the B16 melanoma target cells. These results indicate that DFMO is not immunosuppressive regarding antitumor cytolytic cell induction in vivo. PMID- 3086244 TI - Immunosuppression following 7,12-dimethylbenz[a]anthracene exposure in B6C3F1 mice--II. Altered cell-mediated immunity and tumor resistance. AB - We have previously demonstrated that the polycyclic aromatic hydrocarbons benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) produce a marked decrease in spleen weight, spleen and bone marrow cellularity and the number of IgM plaque forming cells generated in response to a T-dependent antigen. Exposure to DMBA, but not B[a]P, increased susceptibility to challenge with PYB6 tumor cells and Listeria monocytogenes suggesting that DMBA produces immune impairment involving cell-mediated immunity (CMI) and tumor resistance mechanisms. In this study, female B6C3F1 mice received total doses of 5, 50 and 100 micrograms DMBA/g of body weight in ten subcutaneous injections of 0.5, 5, or 10 micrograms/g over a 2 week period and CMI and tumoricidal functions were examined 3-5 days following the final injection of DMBA. DMBA exposed mice exhibited suppressed splenic cellularity (decreased 62%) and decreased numbers of resident peritoneal cells (down to 47% of control), although the proportion of T cell and T cell subsets, B cells and macrophages in spleens from exposed mice was not altered. Lymphocyte blastogenesis in response to mitogens was suppressed up to 49% with PHA, 48% with Con A and 76% with LPS. The response to alloantigens in unidirectional mixed lymphocyte culture was depressed as much as 73% following exposure to DMBA. Tumor cytolysis mediated by cytotoxic T cells (CTL) was impaired at doses of 50 and 100 micrograms DMBA/g body weight (88-95% suppressed respectively) as was natural killer cell (NK)-mediated tumor cytolysis (24% and 55% suppressed). Antibody-dependent cytotoxicity was significantly depressed in the highest exposure group. Peritoneal macrophage accumulation was decreased in DMBA-treated mice, but the macrophages present were pushed towards activation. The ability of DMBA-exposed mice to eliminate intravenously injected B16F10 tumor cells from the lungs was not impaired. Since NK- and M phi-mediated tumor cytotoxicity are thought to be primarily responsible for pulmonary elimination of B16F10 melanoma cells, the extent of NK suppression observed following DMBA exposure appeared to be insufficient to alter in vivo B16F10 pulmonary elimination. In contrast, the loss of the CTL tumoricidal response correlated with an increased frequency of tumors following challenge with PYB6 tumor cells. PMID- 3086245 TI - Lasers--25 years later. PMID- 3086246 TI - 62Zn-EDDA: a radiopharmaceutical for pancreatic functional diagnosis. AB - As Zn is closely associated with the exocrine and endocrine functions of the pancreas, exploitation of Zn metabolism for anatomical and functional diagnosis was conceived, namely with the recent availability of positron emitting 62Zn (t1/2 = 9 h). In the present paper, response changes in Zn biodistribution (mice) and Zn excretion through the pancreatic duct (rats) due to the stimulation of gastro-intestinal hormones like secretin, CCK-PZ (exocrine stimulation) and glucose (endocrine stimulation) were studied. Under these stimuli, the pancreatic secretion of radioactive Zn through cannulated pancreatic duct showed increased Zn secretion only under the CCK-PZ effect, 3 h post 65Zn (t1/2 = 270 d) injection. Tissue biodistribution in mice pre-injected with 65Zn showed pancreas specific decrease of radioactive Zn whenever a gastro-intestinal hormone was post administered, whereas the glucose effect was negligible. Thus, the effective mobilization of the injected radioactive Zn, upon exocrine stimulation, represented by CCK-PZ, favored the exploration of a functional study of the pancreas with the positron computed tomograph (PCT) using short lived nuclide labeled 62Zn-EDDA in dog. Evidence of the applicability of this system in regional function studies of the pancreas was obtained. Demonstration of Zn participation in the exocrine function of the pancreas in-vivo holds considerable promise for diagnosis of pancreatic diseases. PMID- 3086247 TI - A radiopharmaceutical for pancreatic exocrine functional diagnosis: 62Zn-EDDA metabolism in pancreas. AB - The metabolic pathway of radioactive 62Zn-EDDA (ethylenediamine-N,N'-diacetic acid), in the exocrine pancreas was studied with respect to that of endogenous Zn. In pancreatic duct cannulated dog, the secretion of intravenously injected exogenous 62Zn into pancreatic juice increased under the stimulation of CCK-PZ (pancreatic protein secretion stimulating hormone), which closely correlated to endogenous Zn. Moreover, in pancreatic juice, 62Zn as well as endogenous Zn was selectively bound to Zn-metalloenzymes, carboxypeptidase A and B. These results demonstrated the close correlation between the endogenous and the exogenously administered Zn (62Zn-EDDA), as well as the high availability of 62Zn-EDDA as a marker of pancreatic function for the follow up of carboxypeptidase metabolism. PMID- 3086248 TI - Enzymatic formation of ribityl side chain of riboflavin from ribose moiety of nucleotide precursor in Eremothecium ashbyii. AB - Reduction reaction of the ribose moiety of nucleotide precursor to the ribityl side chain of riboflavin, which is believed to be obligatory for riboflavin formation, was followed with crude enzyme from Eremothecium ashbyii. The reaction proceeded with the disappearance of NADPH in the presence of the nucleotides, GTP and ATP, in a Tris-HCl buffer (pH 7.5) at 37 degrees C. Chromatographic analysis of reaction products provides clear evidence that the reduction reaction of ribose to ribitol at the level of nucleotide (or nucleoside) and the cleavage reaction at carbon 8 on the purine ring occurred in the reaction mixture with enzymes from Eremothecium ashbyii. PMID- 3086249 TI - DRGs and outpatient antibiotics. PMID- 3086250 TI - [Silent onset of multiple myeloma. How to diagnosis and when to treat?]. PMID- 3086251 TI - The kinetics of concurrent instantaneous and time dependent inhibition of alkaline phosphatase by urea and related compounds. AB - Urea, thiourea and guanidine-HCl greatly inhibit bone Alkaline Phosphatase activity. The inhibition displays saturation kinetics, fitting a model for the reaction sequence in which formation of complexes with increasing affinity occurs. The time dependent inactivation by urea and guanidine follows pseudo first order kinetics, while thiourea behaviour is better described by a biexponential equation. The pH variation strongly affects the activity, the instantaneous inhibition and the time dependent inactivation. At the pH optimum the three compounds display their strongest effect. Data analysis suggests a three-stage model for the kinetics of Alkaline Phosphatase inhibition by urea and related compounds, involving a consecutive binding process with several sites of the protein and the production of different and interchanging inhibitor-enzyme complexes, leading to irreversibly inactivated forms. PMID- 3086252 TI - Rat haptoglobin: method of quantitation and response to antiarthritic therapy in collagen arthritis. AB - Concentrations of the acute phase reactant haptoglobin were quantitated in the serum of rats using a commercially available antihuman haptoglobin radial immunodiffusion kit. That this antiserum reacted with rat haptoglobin was shown through the techniques of Ouchterlony immunodiffusion and immunoelectrophoresis. Haptoglobin levels were increased seven days after immunization of rats with type II collagen plus incomplete Freund's adjuvant (ICFA) and peaked on day 14. However, even six weeks post-immunization the concentration of haptoglobin was elevated in arthritic rats. A significant correlation was observed between the concentration of serum haptoglobin and the severity of disease (arthritic index) in rats immunized six weeks previously with type II collagen plus ICFA. The effects of antiinflammatory and antirheumatic therapy on arthritic index and serum haptoglobin concentration were determined using a therapeutic dosing protocol. Under these conditions, the known antiarthritic effects of nonsteroidal antiinflammatory drugs, steroids and immunosuppressive agents in this model were confirmed. Of these agents, only the nonsteroidal drugs reduced serum haptoglobin; hydrocortisone, cyclophosphamide and azathioprine elevated haptoglobin. Aurothioglucose, auranofin, and chloroquine, members of the class of disease-modifying antirheumatic drugs, had a general tendency to exacerbate disease, but had minimal effect on serum haptoglobin. D-Penicillamine had little effect on arthritic index and haptoglobin. These results suggest that, while haptoglobin levels do correlate with the intensity of hindpaw swelling, measurement of haptoglobin may not be an accurate indicator of the underlying disease processes in the collagen arthritis model. PMID- 3086254 TI - Product-line administration in hospitals. AB - While a great deal of discussion has centered on product-line planning and management, product-line marketing may be even more important. Defining its market increases the hospital's ability to achieve its mission, improve its vitality, and attract medical staff. By focusing on specific programs or products, the hospital may be able to develop "centers of excellence" that attract patients and referrals from a wide area. PMID- 3086253 TI - Acephalgic migraine. PMID- 3086255 TI - Observations on personnel dosimetry for radiotherapy personnel operating high energy LINACs. AB - A series of measurements were conducted to determine the cause of a sudden increase in personnel radiation exposures. One objective of the measurements was to determine if the increases were related to changing from film dosimeters exchanged monthly to TLD-100 dosimeters exchanged quarterly. While small increases were observed in the dose equivalents of most employees, the dose equivalents of personnel operating medical electron linear accelerators with energies greater than 20 MV doubled coincidentally with the change in the personnel dosimeter program. The measurements indicated a small thermal neutron radiation component around the accelerators operated by these personnel. This component caused the doses measured with the TLD-100 dosimeters to be overstated. Therefore, the increase in these personnel dose equivalents was not due to changes in work habits or radiation environments. Either film or TLD-700 dosimeters would be suitable for personnel monitoring around high-energy linear accelerators. The final choice would depend on economics and personal preference. PMID- 3086256 TI - Returns on equity for not-for-profit hospitals. AB - This study examines the circumstances in which a large third-party payer or regulator might want to set hospital prices to yield a positive rate of return on equity capital. The level of return is shown to depend on the willingness of donors to make funds available in the community relative to the (derived) demand for capital to produce output. It is shown that the appropriate price might well be set to yield a zero or below-market return, and that the return to not-for profit firms should generally be less than that to for-profit firms, if for profit firms are to be active in the market. PMID- 3086257 TI - [Should surgery be done for asymptomatic gallstones?]. PMID- 3086258 TI - Increased acidophilia of eosinophil granules after EDTA treatment. AB - The acidophilic reaction of eosinophil leucocyte granules from human, pig and horse blood smears was investigated by using May-Grunwald-Giemsa staining after previous treatment with EDTA and sodium citrate solutions. The same peak at 530 nm, but absorption values considerably higher than those of controls, were found in eosinophil granules after application of chelating agents, indicating that removal of metal cations could unmask basic groups in these structures. PMID- 3086260 TI - Application of fast protein liquid chromatography to the analysis of water soluble chromium in nonbiological and biological substances. PMID- 3086261 TI - Failure of lactose-restricted diets to prevent radiation-induced diarrhea in patients undergoing whole pelvis irradiation. AB - Sixty-four patients were randomized prior to pelvic radiotherapy into one of three dietary groups: the control group maintained a regular diet except that they drank at least 480 cc of milk daily; the lactose-restricted group was placed on a lactose-restricted diet; and the lactase group drank at least 480 cc of milk with lactase enzyme added to hydrolyze 90% of the lactose. The patients kept records of their stool frequency and the number of diphenoxylate tablets required to control their diarrhea during a 5 week course of standard whole pelvis irradiation. The data does not support the concept that one of the mechanisms of radiation-induced diarrhea associated with pelvic irradiation is a reduction the ability of the intestine to hydrolyze ingested lactose due to the effect of the radiation on the small intestine. There was not a significant difference in stool frequency or diphenoxylate usage among the dietary groups. PMID- 3086259 TI - Cytological, flow cytometric, and molecular analysis of the rapid evolution of mammalian chromosomes containing highly amplified DNA sequences. AB - Transfection of a mouse dihydrofolate reductase (DHFR) cDNA contained in a plasmid "expression vector" into DHFR deficient Chinese hamster cells, followed by progressive selection of cells in increasing concentrations of methotrexate (MTX), leads to marked amplification of the exogenous DHFR sequences in the recipient hamster cells. This gene amplification is evident at the cytological level, in the form of homogeneously staining chromosomal regions (HSRs), at a gene expression level, in the form of fluorescein-methotrexate binding, and at the DNA level. Flow sorting, based on variable fluorescein-MTX binding, or direct cellular cloning, followed by chromosome analysis, revealed intercellular heterogeneity of HSRs in size and distribution. This suggested that there was a rapid evolution of HSRs in MTX-resistant transfectants. Chromosomal analysis of HSR evolution in situ, by examining individual colonies presumably derived from one or a few cells, underscored this impression of chromosome structural fluidity. Rates of HSR change in excess of 0.01 per cell division, increased by low doses of the recombinogen, mitomycin C, were detected. The Chinese hamster DHFR transfectants described should be amenable to detailed, coordinate cytological and molecular characterization. Such an analysis should contribute to an understanding of processes such as homologous recombination in mediating HSR evolution in mammalian chromosomes. PMID- 3086262 TI - Breast irradiation following silicone gel implants. AB - Little information is found in the literature regarding breast irradiation in patients with reconstructed or augmented breasts. From November 1970 to October 1984, we treated ten patients with silicone gel prostheses with external radiation for recurrent disease, or as primary therapy. All patients were treated with megavoltage equipment. Technique and doses varied with the clinical situation, but generally, patients received 5000 rad in five weeks to the breast or mound with opposed tangential fields. The majority of patients had excellent cosmetic results with minimal late skin changes and no fibrosis or contracture. We conclude that, with proper surgical and radiotherapeutic techniques, good cosmetic results can be obtained in these patients, without compromising their therapy. PMID- 3086263 TI - Superovulation and embryo transfer in the dairy goat. AB - Eighteen mature, purebred (Saanen, Alpine, Nubian, La Mancha) dairy does were estrus-regulated with progesterone-impregnated vaginal pessaries. On treatment days 16 to 18, superovulation of 6 does was attempted with pregnant mare's serum gonadotropin (PMSG), and of 12 does with follicle stimulating hormone (FSH). Estrus was induced by progesterone withdrawal on days 18 to 20 and the does were mated to bucks of proven fertility. Embryos were recovered from oviduct flushings on the fourth day after mating. The yield of 4- to 12-cell embryos with FSH superovulation was 17(+/- 2), significantly greater (P less than 0.001) than with PMSG, which was 2(+/- 2). Thirty-six embryos from 3 FSH donor does were transferred to 14 recipients that were estrus-regulated to the donor cycles with the same progesterone pessary regimen. Eleven (78%) of the recipients became pregnant and delivered 21 (70%) kids from 40 embryos, a mean of 7(+/- 2)/donor. PMID- 3086264 TI - Nonsteroidal antiinflammatory drugs, prostaglandins, and the kidney. PMID- 3086265 TI - Biosynthesis of the avermectins by Streptomyces avermitilis. Incorporation of labeled precursors. AB - The biosynthesis of the avermectins, a group of 16 membered macrolides with potent anthelmintic and insecticidal activity produced by Streptomyces avermitilis, was studied by supplying cultures with 14C and 13C precursors. [1 14C] and [2-14C]acetate and propionate were poor precursors of the avermectins and were instead rapidly oxidized to 14CO2. The S-methyl of methionine in contrast was incorporated extensively and equally into the three methoxyl groups of the avermectins. The carbon backbone of methionine was not a precursor of the avermectins. Feeding of [1-13C]glucose yielded avermectins labeled specifically in the C1' and C1" of the oleandrose moiety and in the aglycone moiety in carbons known to be derived from the methyl of acetate. Feeding [U-13C]glucose showed that the entire avermectin molecule is derived from glucose carbons. PMID- 3086266 TI - Studies on lipoxygenase inhibitors. I. MY3-469 (3-methoxytropolone), a potent and selective inhibitor of 12-lipoxygenase, produced by Streptoverticillium hadanonense KY11449. AB - Streptoverticillium hadanonense KY11449 was found to produce a 12-lipoxygenase inhibitor MY3-469. The compound was purified by chromatography on Diaion HP-10, charcoal, Sephadex LH-20 and crystallization. The chemical structure of MY3-469 was determined to be 3-methoxytropolone on the basis of its physico-chemical properties. The half maximal inhibitory concentration (IC50) of MY3-469 against bovine platelet 12-lipoxygenase was 1.8 X 10(-6)M. The compound did not inhibit bovine platelet cyclooxygenase at 10(-3)M and showed weak inhibition (IC50 2.8 X 10(-4)) against 5-lipoxygenase of rat basophilic leukemia cells. The results indicate that MY3-469 is a potent and selective inhibitor of 12-lipoxygenase. PMID- 3086267 TI - Serum concentrations of prolactin, thyroxine and triiodothyronine relative to season and the estrous cycle in the mare. AB - Studies were conducted to characterize circulating concentrations of prolactin, thyroxine (T4) and triiodothyronine (T3) relative to season and the estrous cycle, and to evaluate the ability of thyrotropin-releasing hormone (TRH) to induce prolactin secretion in the horse mare. The increase in serum prolactin following the iv injection of 0, 5, 50 and 500 micrograms TRH was dose-related, while all three doses of TRH induced a significant and comparable increase in serum T4. Seasonal variations in serum prolactin were directly correlated (P less than .001) with changes in photoperiod (r = .80) and temperature (r = .61). By comparison, concentrations of T3 were inversely related to temperature (r = -.49; P less than .001), while changes in T4 were less closely associated with photoperiod (r = -.29; P = .04). There were no significant fluctuations in prolactin, T3 or T4 at any stage of the estrous cycle. These results demonstrate that concentrations of prolactin in the mare are highest during the summer and lowest during the winter, but it is unknown whether this annual rhythm is controlled by photoperiod, temperature and(or) other environmental factors. PMID- 3086269 TI - Effects of rumen-protected methionine and lysine on ruminant performance and nutrient metabolism. AB - Four trials were conducted to determine the effects of supplemental rumen protected methionine (RPMet) and lysine (RPLys) on lamb N metabolism and steer feedlot performance. In trial 1, 20 Suffolk-sired, crossbred lambs (avg weight 32 kg) were fed diets containing no supplemental methionine (Met) and lysine (Lys), .03% RPMet, .05% RPLys or .03% RPMet + .05% RPLys. Lambs fed .03% RPMet + .05% RPLys had a 33% increase in N retention compared with lambs fed no supplemental Met and Lys. In trial 2, to verify the protection and availability of these amino acids, five Targhee lambs (avg weight 35 kg) were fed corn-soybran flake diets supplemented with urea and were assigned in a 5 X 5 Latin square to one of the following treatments: 1) control; 2) .03% RPMet + .05% RPLys offered in the diet; 3) .03% RPMet + .05% RPLys abomassally infused; 4) .03% non-protected Met + .05% non-protected Lys offered in the diet and 5) .03% Met + .05% Lys abomasally infused. Treatments 2, 3 and 5 decreased (P less than .05) urinary N (g/d) and increased N retention (P less than .05) compared with the control diet (treatment 1). Increases (P less than .05) in plasma Met and Lys concentrations indicated that the amino acids were protected and available for animals at the site of absorption. In trial 3, 40 crossbred Angus steers (avg weight 247 kg) were fed diets composed of 53% corn silage and 47% concentrate and supplemented with soybean meal to 11.3% crude protein. Steers that were fed diets containing .19% RPMet + .11% RPLys had greater daily gain (P less than .05) than those fed diets containing no supplemental amino acids, .11% RPMet + .01% RPLys, and .15% RPMet + .06% RPLys (1.39 vs 1.23, 1.22 and 1.20 kg/d, respectively). Similar improvements in feed conversion resulted and increases in plasma Met concentrations followed the same trend. In trial 4, 40 crossbred Angus steers (avg weight 368 kg) were fed corn grain-corn silage diets supplemented with urea. Treatments were: no supplemental amino acids; .05% RPMet + .01% RPLys; .10% RPMet + .04% RPLys; and .15% RPMet + .07% RPLys. No differences in steer performance resulted due to supplemental RPMet and RPLys (P greater than .05). The results of these trials suggest that the RPMet and RPLys used in this study are protected from ruminal degradation, are available post-ruminally and can improve lamb N balance and growing steer performance. PMID- 3086268 TI - Pulsatile or continuous infusion of luteinizing hormone-releasing hormone and hormonal concentrations in prepubertal beef heifers. AB - An experiment was conducted to determine if exogenous luteinizing hormone releasing hormone (LHRH) administered iv intermittently as pulses (P) or by continuous sc infusion (I) using osmotic minipumps could sustain pulsatile LH release and induce estrous cyclicity in prepubertal heifers. Prepubertal heifers were assigned randomly to: 1) receive pulses of LHRH (n = 6; 2.5 micrograms LHRH/2 h for 72 h), 2) be infused with LHRH (n = 11; 1.25 micrograms LHRH/h for 72 h), or 3) serve as controls (n = 16). Blood was collected at 20-min intervals for 8 h (0900 to 1700 h) from six heifers in each group on d 1, 2, 3 (during treatment), and on d 4 (during 8 h after terminating LHRH treatments). Heifers given LHRH had higher (P less than .01) LH concentrations than controls. Preovulatory-like LH surges occurred in three I, two P and no control heifers during treatment. Pulse frequencies of LH (no. LH pulses/8 h) were greater (P less than .001) for P heifers than for I and control heifers due to pulsatile LHRH treatment. Serum estradiol was higher (P less than .01) during treatment for LHRH-treated heifers than for controls. Serum follicle-stimulating hormone, cortisol, and progesterone were unchanged during treatment. High levels of cortisol on d 1 declined (P less than .001) to baseline by d 2. Characteristic progesterone rises or short luteal phases occurred within 10 d of treatment initiation in more (P less than .05) LHRH-treated heifers (I = 45%, P = 33%) than controls (6%), although days to first observed estrus and first ovulation were unaffected by treatments. Although both continuous and pulsatile administration of LHRH successfully induced LH and estradiol release as well as preovulatory like LH surges in some heifers, earlier initiation of estrous cycles was not achieved. Estrous cycles appeared to be delayed by exposure to continuous LHRH infusions during the peripubertal period. PMID- 3086270 TI - The metabolism of carbaryl by three bacterial isolates, Pseudomonas spp. (NCIB 12042 & 12043) and Rhodococcus sp. (NCIB 12038) from garden soil. AB - At an alkaline pH and in aqueous solution, carbaryl hydrolyses to form 1 naphthol, methylamine and carbon dioxide, but it is much more stable at an acid pH. Two bacterial isolated from garden soil, Pseudomonas sp. (NCIB 12042) and Rhodococcus sp. (NCIB 12038), could grow on carbaryl as sole carbon and nitrogen source at pH 6.8 but failed to metabolize carbaryl rapidly. Both could use 1 naphthol as sole carbon source and NCIB 12042 metabolized 1-naphthol via salicylic acid which induced higher expression of enzymes in the pathway. Strain NCIB 12038 metabolized 1-naphthol via salicylic and gentisic acids. In contrast, Pseudomonas sp. (NCIB 12043) was selected in a soil perfusion column enrichment at pH 5.2 and metabolized carbaryl rapidly to 1-naphthol and methylamine. 1 Naphthol was metabolized via gentisic acid. Neither salicylate nor gentisate induced higher expression of enzymes for 1-naphthol catabolism in NCIB 12038 and NCIB 12043. PMID- 3086271 TI - Detection and enumeration of Listeria monocytogenes in a sewage treatment plant in Iraq. AB - Listeria monocytogenes was isolated from a sewage treatment plant in Baghdad, Iraq, at all stages of treatment. The treatment processes did not yield a sewage sludge cake or a final discharge free of listerias. The agricultural practice of using such sewage products as fertilizers could become a route of spreading the organism in Iraq, particularly by infecting animals that consume vegetation in fields spread with such sewage. Dewatering of sewage reduced the number of L. monocytogenes but long periods of exposure to sun would be needed to obtain a 'safe' sewage sludge cake. PMID- 3086272 TI - New plasmid-mediated oxacillin-hydrolyzing beta-lactamase in Pseudomonas aeruginosa. AB - A novel type of oxacillin-hydrolyzing beta-lactamase, termed OXA-4, has been detected in three Pseudomonas aeruginosa strains isolated in Paris between 1977 and 1981. The strains contained similar plasmids that determined resistance to carbenicillin, chloramphenicol, gentamicin, kanamycin, streptomycin, sulphonamide, tetracycline, tobramycin, sodium borate, and mercuric chloride, had a size of approximately 150 megadaltons, and belonged to the P-5 incompatibility group. Compared to reference OXA-1 beta-lactamase produced by plasmid RGN238, OXA 4 beta-lactamase produced by these plasmids had a similar substrate profile, similar response to inhibitors, and identical immunological reactions but differed in isoelectric point. In a more recent survey of 10 French hospitals plasmid-determined OXA-4 beta-lactamase production was found in P. aeruginosa isolates from four hospitals in the Paris area. PMID- 3086273 TI - Bactericidal and bacteriolytic activities of carumonam and its effect on bacterial morphology. AB - The in-vitro bactericidal and bacteriolytic activities and the effect on bacterial morphology of carumonam, a new N-sulfonated monocyclic beta-lactam antibiotic, against aerobic Gram-negative bacilli were compared with those of aztreonam. Both antibiotics, at their minimal inhibitory concentration (MIC) levels, were strongly bactericidal against species of Enterobacteriaceae, but weakly bactericidal against Pseudomonas aeruginosa. Their bactericidal activity was not increased by increasing the antibiotic concentration above the MICs. In contrast to this potent bactericidal activity, the bacteriolytic activity of carumonam and aztreonam was low and limited to enteric bacterial species like Escherichia coli. Filamentation was the major morphological change of Gram negative bacilli after exposure to carumonam and aztreonam. E. coli and Serratia marcescens, but not P. aeruginosa, were converted to ghosts after prolonged incubation with carumonam. PMID- 3086274 TI - An epidemic spread of multiresistant Pseudomonas aeruginosa in a cystic fibrosis centre. AB - Early in 1983 an epidemic of a Pseudomonas aeruginosa resistant to aminoglycosides, carbenicillin, ureidopenicillins, ceftazidime, cefsulodin and imipenem occurred in a cystic fibrosis centre. Most of the epidemic could be attributed to a specific nosocomial strain by means of O-grouping and phage typing. This strain was present in the centre at a low frequency in 1973 and developed resistance during courses of chemotherapy. The epidemic was stopped by isolating patients with the resistant strains. Restrictive and selective use of antibiotics have not been sufficient to eradicate the resistant strains, which persist in 42% of the patients. The extensive use of the third generation cephalosporins in the clinic is probably responsible for inducing and selecting for the resistant strains. Clustering of patients in the centre has facilitated the spread. First-line use of older beta-lactam antibiotics, close bacteriological monitoring and prompt isolation of patients with resistant strains are recommended. PMID- 3086275 TI - In-vitro studies of antibiotic combinations with special emphasis on the evaluation of newly developed methods. AB - We have described an in-vitro pharmacokinetic model that mimics the serum and tissue concentrations of antibiotics during therapy of human patients, and thus presents a changing concentration of antibiotics to the bacterial inoculum. This pharmacokinetic model has been used to study antibiotic combinations that are used in the treatment of infections in granulocytopenic patients. In this model the addition of piperacillin to amikacin or of ceftazidime or azlocillin to another aminoglycoside prevented the regrowth of resistant subpopulations of Pseudomonas aeruginosa. The activities of several antibiotic combinations were studied in the in-vitro model, the conventional checker-board method and the time kill method. Discrepant results were found with the model and the conventional tests in one-third of the combinations. The model may be useful in the preclinical study of antibiotic combinations and may be proved more predictive of clinical outcome than conventional tests. PMID- 3086276 TI - Emergence of resistance after therapy with antibiotics used alone or combined in a murine model. AB - A murine model of peritonitis allowing detection and quantification of in-vivo acquired resistance during short term therapy has been used in order to evaluate the capacity of antimicrobial combinations to limit emergence of resistance, as compared to individual components of the regimens. Mice were challenged intraperitoneally with 10(8) cfu of bacteria. Two hours later, a single antibiotic dose was injected subcutaneously: amikacin (15 mg/kg), ceftriaxone (50 mg/kg), pefloxacin (25 mg/kg), amikacin + ceftriaxone, amikacin + pefloxacin or ceftriaxone + pefloxacin. Escherichia coli and Staphylococcus aureus never became resistant. Single drug therapy yielded resistant mutants in Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae and Pseudomonas aeruginosa as follows: 74% of ceftriaxone-treated animals, 57% of pefloxacin treated animals and 27% of amikacin treated animals. All the tested combinations reduced the frequency of in vivo acquired resistance produced by single drugs, and no combination selected resistance when the separate agents of the combination did not. Combining antimicrobial agents limits the risk of emergence of resistance during antibiotic therapy. PMID- 3086277 TI - Ureidopenicillins, aztreonam, and thienamycin: efficacy as single-drug therapy of severe infections and potential as components of combined therapy. AB - The ureidopenicillins (piperacillin, mezlocillin, and azlocillin), aztreonam, and thienamycin are new broad-spectrum beta-lactams with more potent antibacterial activity than the older cephalosporins and penicillins. However, therapy of severe infections with the ureidopenicillins alone is limited by the potential for emergence of resistant organisms, while monotherapy with aztreonam does not provide adequate coverage for Gram-positive aerobic organisms and anaerobes. In combination therapy with the aminoglycosides, the ureidopenicillins may be preferred to carbenicillin or ticarcillin in the treatment of Pseudomonas aeruginosa infections and in institutions with a high prevalence of carbenicillin or ticarcillin-resistant organisms. Double beta-lactam therapy with piperacillin plus either latamoxef (moxalactam) or ceftazidime may be advantageous in patients for whom aminoglycoside toxicity is a concern. Thienamycin is the most promising of the new beta-lactams for single-agent therapy of severe infections but may also be associated with the emergence of resistant P. aeruginosa during monotherapy. In febrile granulocytopenic patients or other severely ill patients at risk of severe P. aeruginosa infections, thienamycin or another antipseudomonal beta-lactam should be combined with an aminoglycoside. PMID- 3086278 TI - In-vitro activity of pefloxacin against micro-organisms multiply resistant to beta-lactam antibiotics and aminoglycosides. AB - The in-vitro activity of pefloxacin was evaluated against 360 Enterobacteriaceae, 143 Pseudomonas aeruginosa and 124 staphylococci, selected for multiply resistance to different beta-lactam antibiotics and aminoglycosides. The MIC90 of pefloxacin against staphylococci and most Enterobacteriaceae was 0.5 mg/l or less. The MIC90 against Serratia marcescens and P. aeruginosa varied between 4 and 8 mg/l. Time-killing curves showed that pefloxacin at concentrations of four times the MIC decreased the viable counts by 3 logs or more within 1-8 h. PMID- 3086279 TI - In-vitro activity of pefloxacin compared to other antibiotics. AB - Pefloxacin is a new quinolone carboxylic acid with a broad spectrum of antibacterial activity. A comparison was made of the in-vitro activity of pefloxacin and that of nine other antibiotics (ampicillin, ticarcillin, piperacillin, cefazolin, cefotaxime, ceftazidime, gentamicin, amikacin and norfloxacin). The MIC90 of pefloxacin against 500 strains of Enterobacteriaceae ranged from 0.25 mg/l (Escherichia coli, indole + Proteus spp., Enterobacter cloacae, Salmonella spp. and Shigella spp.) to 1 mg/l (Klebsiella pneumoniae). Pefloxacin inhibited 90% of 52 strains of Pseudomonas aeruginosa at 2.5 mg/l (range 0.25 mg/l-4 mg/l). The MIC90 of pefloxacin against 100 Staphylococcus aureus strains (78 oxacillin resistant strains) was 0.4 mg/l (range 0.12-0.5 mg/l). It was markedly less active against Streptococcus faecalis and Str. pneumoniae (37 strains of each species) the MIC90 being 4 mg/l against both species. Overall, pefloxacin was at least as active as the third-generation cephalosporins against Enterobacteriaceae and was more active than any other antibiotic tested against P. aeruginosa, S. epidermidis, and S. aureus. Against E. coli, pefloxacin had a more rapid anti-bacterial activity than piperacillin. A paradoxical effect was observed with pefloxacin. An optimal killing rate was observed at concentrations of pefloxacin compatible with those one can expect in blood of patients treated with this drug. PMID- 3086280 TI - The diffusion of pefloxacin into bone and the treatment of osteomyelitis. AB - Pefloxacin was evaluated in the treatment of bone infections. A clinical trial was performed in 15 patients with chronic osteitis (5 Staphylococcus aureus, 5 Pseudomonas aeruginosa, 3 Serratia sp., 1 Proteus mirabilis, and a mixed infection with a Streptococcus faecalis and Escherichia coli). Patients were given pefloxacin 400 mg 12-hourly iv for 48 h followed by oral treatment. Bone biopsies from the iliac crest were carried out after at least seven days treatment, 2 h after the last dose. Serum levels were estimated at the same time. In 13 patients the pefloxacin levels were between 2 and 10 mg per g of bone and always greater than, or equal to, the MIC for the infecting organism. In 11 patients treated for six months and followed up for up to 14 months after the completion of treatment, the therapy was successful. In another two patients, the results were excellent with closure of fistulae, but there was only limited follow-up. There were two failures: in one (post-radiation osteitis) the infection persisted and in the other there was intolerance of the antimicrobial. In both cases there was no increase in the MIC of pefloxacin against the organisms. Three patients underwent operations for orthopaedic indications, after at least two months of treatment. Bone cultures from the initial focus remained sterile. Side-effects were mild. PMID- 3086281 TI - Pyruvate metabolism of perfused rat lungs after exposure to 100% oxygen. AB - Previous studies with lung homogenates have suggested that pulmonary O2 toxicity is in part a result of inhibited mitochondrial energy metabolism. In this study, mitochondrial metabolism was determined by measurements of 14CO2 production from [1-14C]-pyruvate in perfused lungs, isolated after 0, 3, 6, 12, and 24 h of exposure to 100% O2. Measurements were made under normal and stimulated conditions brought about by uncoupling oxidative phosphorylation with 2,4 dinitrophenol (DNP). Lungs were ventilated with 5% CO2 in O2 and perfused for 100 min with 12.5 mM 14C labeled pyruvate. Unexposed lungs gave a linear rate of 14CO2 production of 121 +/- 16 mumol/h/g dry wt (n = 5), which was maximally stimulated 84% by perfusion with 0.8 mMDNP. Twenty-four hours of exposure to 100% O2 did not significantly affect 14CO2 production. In contrast, DNP failed to significantly stimulate pyruvate metabolism to CO2 in lungs exposed for greater than 3 h to 100% O2. These latter data suggested that O2 exposure makes lung mitochondria unable to respond to increased ATP demands associated with DNP uncoupling. Compromised energy metabolism is therefore an important early event in O2 toxicity. PMID- 3086282 TI - Respiratory arrhythmias and airway CO2, lung receptors, and central inspiratory activity. AB - The purpose of this study was to determine whether hypocapnia affects heart rate secondary to an effect on pulmonary receptors. Dogs were anesthetized and placed on cardiopulmonary bypass. Interrelationships among airway CO2, central inspiratory activity, and lung receptor effects on respiratory-related heart rate changes (respiratory arrhythmias) were studied after vagal efferent activity was increased secondary to baroreceptor stimulation. Hypocapnia, isolated to the lungs, produced an increase in the magnitude of the respiratory arrhythmias observed. Two mechanisms may produce these results. Hypocapnia affects pulmonary receptors, which 1) reflexly alter heart rate and 2) modulate breathing frequency, thus altering the dynamics of the respiratory arrhythmias that were produced. The results also suggested that the reflex increase in heart rate in response to lung inflation and the Hering-Breuer expiratory-facilitatory reflex are either produced by different pulmonary receptors or by the same pulmonary receptors but may be mediated by different central mechanisms. PMID- 3086283 TI - A fundamental problem in determining functional residual capacity or residual volume. AB - To measure a lung volume that is not directly accessible, one often follows dilution of a single-gas tracer, present initially only in the lung or in a rebreathing bag. The final volume available to the tracer is assumed to be the sum of the two initial components. Since O2 is taken up and CO2 is eliminated during the few breaths required for mixing, the total volume changes. The error in lung volume due to this volume change can exceed 10%. In this paper we 1) present theoretical and experimental data to demonstrate the effect of CO2 and O2 exchange, 2) introduce a general equation, based on N2 and Ar, which allows one to circumvent the problems created by these fluxes, and 3) show the pitfall of the back-extrapolation approach for a single tracer. PMID- 3086284 TI - [Soft-tissue chondromas of the hand. Anatomo-radiological study]. PMID- 3086285 TI - Influence of modification next to the anticodon in tRNA on codon context sensitivity of translational suppression and accuracy. AB - Effects on translation in vivo by modification deficiencies for 2-methylthio-N6 isopentenyladenosine (ms2i6A) (Escherichia coli) or 2-methylthio-N6-(4 hydroxyisopentenyl)adenosine (ms2io6A) (Salmonella typhimurium) in tRNA were studied in mutant strains. These hypermodified nucleosides are present on the 3' side of the anticodon (position 37) in tRNA reading codons starting with uridine. In E. coli, translational error caused by tRNA was strongly reduced in the case of third-position misreading of a tryptophan codon (UGG) in a particular codon context but was not affected in the case of first-position misreading of an arginine codon (CGU) in another codon context. Misreading of UGA nonsense codons at two different positions was codon context dependent. The efficiencies of some tRNA nonsense suppressors were decreased in a tRNA-dependent manner. Suppressor tRNA which lacks ms2i6A-ms2io6A becomes more sensitive to codon context. Our results therefore indicate that, besides improving translational efficiency, ms2i6A37 and ms2io6A37 modifications in tRNA are also involved in decreasing the intrinsic codon reading context sensitivity of tRNA. Possible consequences for regulation of gene expression are discussed. PMID- 3086286 TI - Ultrastructure of the cell envelope of the archaebacteria Thermoproteus tenax and Thermoproteus neutrophilus. AB - The ultrastructures of the regular surface layers (S-layers) of the extremely thermophilic archaebacteria Thermoproteus tenax and Thermoproteus neutrophilus were examined by freeze-etching, freeze-drying, and negative staining methods combined with optical and digital image enhancement. In both strains, a monolayer of macromolecules arranged in hexagonal arrays with center-to-center spacings of approximately 30 nm was the only component of the cell wall. The gross morphologies of the S-layer lattices of the two organisms were similar and showed the same handedness in the arrangement of the protomers of the morphological units. Striking differences were found in the anionic charge distributions on the surfaces of the two S-layer proteins as determined by labeling with polycationic ferritin. Analysis of the lattice orientation, together with the number and distribution of lattice faults on intact cells, provided a strong indication that the S-layers of both organisms have a shape-determining function. PMID- 3086287 TI - Nucleotide sequence of the gene for cytochrome b558 of the Bacillus subtilis succinate dehydrogenase complex. AB - The nucleotide sequence was determined for the first part of the Bacillus subtilis sdh operon. An open reading frame corresponding to the structural gene, sdhA, for cytochrome b558 was identified. The predicted molecular weight of the cytochrome (excluding the N-terminal methionine) is 22,770. It is a very hydrophobic protein with five probable membrane-spanning segments. There is little homology between the B. subtilis cytochrome b558 and cytochrome b of mitochondrial complex III from different organisms or between cytochrome b558 and the hydrophobic sdhC and sdhD peptides of the Escherichia coli sdh operon. About 30 bases downstream of the sdhA stop codon, a new open reading frame starts. The nucleotide sequence predicts the presence of a typical flavin-binding peptide which identifies this reading frame as part of the sdhB gene. Seven bases upstream of the sdhA initiation codon ATG there is a typical B. subtilis ribosome binding site (free energy of interaction, -63 kJ), and further upstream, tentative sigma 55 and sigma 32 promoter sequences were found. The upstream region also contains two 12-base-long direct repeats; their significance is unknown. PMID- 3086288 TI - Structure of a beta-galactosidase gene of Bacillus stearothermophilus. AB - The nucleotide sequence of the bgaB gene, which encodes the thermostable beta galactosidase I of Bacillus stearothermophilus, and its flanking region was determined. A 2,016-base-pair open reading frame observed was concluded to be for beta-galactosidase I (Mr 78,051) from observations that the amino acid composition of the enzyme and the sequence of 14 amino acids from the amino terminus of the enzyme coincided with those deduced from this open frame. A 107 base-pair HaeIII-AluI fragment just upstream of the estimated Shine-Dalgarno sequence of the bgaB gene had promoter activity toward cat-86 (chloramphenicol acetyltransferase gene) and produced the enzyme at a level equivalent to 7% of the total cellular protein of B. subtilis. From the base sequence of this DNA region and the transcriptional start site determined by S1 nuclease mapping, the 35 and -10 sequences are estimated to be TTGACA and TAATTT, respectively, which are similar to the consensus sequence of B. subtilis sigma 43 RNA polymerase. PMID- 3086289 TI - Adenosine accumulation in Saccharomyces cerevisiae cultured in medium containing low levels of adenine. AB - By monitoring the in vivo incorporation of low concentrations of radiolabeled adenine into acid-soluble compounds, we observed the unusual accumulation of two nucleosides in Saccharomyces cerevisiae that were previously considered products of nucleotide degradation. Under the culture conditions used in the present study, radiolabeled adenosine was the major acid-soluble intracellular derivative, and radiolabeled inosine was initially detected as the second most prevalent derivative in a mutant lacking adenine aminohydrolase. The use of yeast mutants defective in the conversion of adenine to hypoxanthine or to AMP renders very unlikely the possibility that the presence of adenosine and inosine is attributable to nucleotide degradation. These data can be explained by postulating the existence of two enzyme activities not previously reported in S. cerevisiae. The first of these activities transfers ribose to the purine ring and may be attributable to purine nucleoside phosphorylase (EC 2.4.2.1) or adenosine phosphorylase (EC 2.4.2.-). The second enzyme converts adenosine to inosine and in all likelihood is adenosine aminohydrolase (EC 3.5.4.4). PMID- 3086290 TI - Cell-cycle-specific oscillation in the composition of chromatophore membrane in Rhodospirillum rubrum. AB - Synchrony in phototrophic cultures of Rhodospirillum rubrum was induced by stationary-phase cycling or by alterations in light intensity. Intracytoplasmic chromatophore membranes were prepared by differential centrifugation. Analysis of the composition of chromatophores obtained from cells at different times indicated that the protein/bacteriochlorophyll a ratio was constant throughout the cell cycle but that the protein/phospholipid ratio oscillated. This cell cycle-dependent fluctuation in chromatophore membrane composition was reflected in the buoyant densities of the isolated chromatophores. PMID- 3086291 TI - Association of RNA polymerase having increased Km for ATP and UTP with hyperexpression of the pyrB and pyrE genes of Salmonella typhimurium. AB - We investigated the transcription kinetics of RNA polymerase from an rpoBC mutant of Salmonella typhimurium which showed highly elevated, constitutive expression of the pyrB and pyrE genes as well as an increased cellular pool of UTP. When bacterial cultures containing an F' lac+ episome were induced for lac operon expression, the first active molecules of beta-galactosidase were formed with a delay of 73 +/- 3 s in rpo+ cells. The corresponding time was 104 to 125 s for cells carrying the rpoBC allele, indicating that this mutation causes a reduced RNA chain growth rate. In vitro the purified mutant RNA polymerase elongated transcripts of both T7 DNA and synthetic templates more slowly than the parental enzyme at a given concentration of nucleoside triphosphates. This defect was found to result from four- to sixfold-higher Km values for the saturation of the elongation site by ATP and UTP. The saturation kinetics of the RNA chain initiation step also seemed to be affected. The maximal elongation rate and Km for GTP and CTP were less influenced by the rpoBC mutation. Open complex formation at the promoters of T7 DNA and termination of the 7,100-nucleotide transcript showed no significant difference between the parental and mutant enzymes. Together with the phenotype of the rpoBC mutant, these results indicate that expression of pyrB and pyrE is regulated by the mRNA chain growth rate, which is controlled by the cellular UTP pool. The rate of gene expression is high when the saturation of RNA polymerase with UTP is low and vice versa. PMID- 3086292 TI - 5'-noncoding region sacR is the target of all identified regulation affecting the levansucrase gene in Bacillus subtilis. AB - The regulation of the levansucrase gene sacB was studied in Bacillus subtilis strains. Fusions were constructed in which genes of cytoplasmic proteins such as lacZ were placed immediately downstream from sacR, the regulatory region located upstream from sacB. These fusions were introduced in mutants affected in sacB regulation. In all cases the marker gene was affected in the same way as sacB by the genetic context. This result is of particular interest for the sacU pleiotropic mutations, which affect sacB expression and other cellular functions such as the synthesis of several exocellular enzymes. We also showed that strains harboring sacU+ or sacU-hyperproducing alleles contained different amounts of sacB mRNA, which was proportional to their levansucrase secretion. We concluded that the sacU gene does not affect sacB expression at the level of secretion but acts on a target within sacR. We discuss the possibility that sacU acts on a part of sacR, a homologous copy of which was found upstream from the gene of another sacU-dependent secreted enzyme of B. subtilis, beta-glucanase. PMID- 3086293 TI - Non-bulimia: food regurgitation in a patient with self-diagnosed bulimia. AB - The increased prevalence of bulimia has received great publicity by the news media. Such publicity predisposes individuals to self-diagnosis. A 57-year-old man with a 10-year history of food regurgitation presented to an eating disorder clinic complaining of bulimia, which he had heard discussed on a television talk show. He proved not to have bulimia but a large pharyngoesophageal (Zenker's) diverticulum. The diagnosis of bulimia may be misattributed to various symptoms by patients. The differential diagnosis of chronic regurgitation and vomiting must be considered in such patients. PMID- 3086294 TI - Effects of calmodulin antagonists on serine phospholipid base-exchange reaction in rabbit platelets. AB - Effects of the calmodulin antagonists chlorpromazine, trifluoperazine, and N-(6 aminohexyl)-5-chloro-1-naphthalenesulfonamide on phospholipid metabolism were examined in rabbit platelets using [3H]serine, [3H]ethanolamine, [3H]choline, and [3H]glycerol. All these drugs markedly stimulated the incorporation of [3H]serine into phosphatidylserine. On the other hand, these drugs had only a slight effect on the rate of incorporation of [3H]ethanolamine and [3H]choline into the corresponding phospholipid. When [3H]glycerol was used as a precursor of the phospholipids, 3H-labeled phospholipids were mainly composed of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. Although the phosphorus content of phosphatidylserine was about 40% of that of phosphatidylcholine in rabbit platelets, the amount of phosphatidylserine labeled with [3H]glycerol was less than 2% of that of the labeled phosphatidylcholine, and calmodulin antagonists slightly stimulated the incorporation of [3H]glycerol into phosphatidylserine. Treatment with calmodulin antagonists caused a marked decrease in the content of endogenous free serine with concomitant increase in the contents of endogenous free ethanolamine and choline. On the other hand, the contents of other free amino acids, including essential and non-essential amino acids, were unchanged. These results suggest that the calmodulin antagonists we used did not affect de novo synthesis of phosphatidylserine, but did stimulate the serine phospholipid base-exchange reaction in rabbit platelets. PMID- 3086295 TI - Structural studies on N-acetylmannosaminuronic acid-containing and glucuronic acid-containing teichuronic acids in the cell wall of Bacillus megaterium AHU 1375. AB - Structural studies were carried out on two kinds of teichuronic acid-glycopeptide complexes (designated as TU-GP-I and TU-GP-II) isolated from lysozyme digest of N acetylated cell walls of Bacillus megaterium AHU 1375 by ion-exchange chromatography and gel chromatography. TU-GP-I, accounting for about 25% of the cell walls, contained N-acetylmannosaminuronic acid, N-acetylglucosamine, glucose, galactose, glycerol, and phosphorus in an approximate molar ratio of 1:1:2:1:0.5:0.5, together with small amounts of glycopeptide components. TU-GP II, accounting for about 9% of the cell walls, contained glucuronic acid, glucose, and fucose in a molar ratio of about 2:1.5:1, together with small amounts of glycopeptide components. The results of analyses involving Smith degradation, chromium oxidation, methylation, acetolysis, and H-NMR measurement led to the conclusion that the polysaccharide chain of TU-GP-I comprised repeating units,----6) Glc(alpha 1----3)-ManNAcUA(beta 1----4)[Gal(alpha 1--- 3)][Glc(beta 1----6)]GlcNAc(beta 1----. About half of the repeating units were substituted by glycerophosphoryl residues at C-6 of the beta-glucosyl residues linked to the N-acetylglucosamine residues. By means of a similar procedure, the polysaccharide chain of TU-GP-II was shown to comprise repeating units,--- 4)GlcUA(alpha 1----3)GlcUA(alpha 1----3)Glc(alpha 1----3)Fuc(alpha 1----, of which about half were substituted by alpha-glucosyl residues at C-3 of the 4 substituted glucuronosyl residues. PMID- 3086296 TI - Biochemical diagnosis of cerebrotendinous xanthomatosis using reversed phase thin layer chromatography. AB - We developed a simple quantitative procedure for cholestanol in serum involving reversed phase thin layer chromatography. This procedure was satisfactory with regard to the linearity of the calibration curve in the range of 100 ng to 1,000 ng, recovery and reproducibility. Only 100 microliter of serum was needed for determination of the cholestanol concentration. Prior to thin layer chromatography, cholesterol was converted to alpha- and beta-epoxides with m chloroperbenzoic acid, which were clearly distinguishable from cholestanol on TLC. Detection of sterols was performed by spraying with phosphomolybdic acid solution. Quantification of cholestanol was carried out with a TLC scanning densitometer. When serum cholestanol in cerebrotendinous xanthomatosis (CTX) patients was quantified by TLC, GC-MS, and GC, the correlation among the three methods was found to be approximately 1:1:1. It was found that the present method was useful for the primary diagnostic screening of CTX because of its simplicity and because many samples could be analyzed at one time. PMID- 3086297 TI - Determination of an antibody-antigen binding constant by enzyme immunoassay and a theory for analysis of competitive binding of two ligands to heterogeneous receptor. AB - A method for determining antigen-antibody binding constants by using enzyme labeled antigens has been developed. In the measurement, enzyme-labeled and unlabeled antigens (Ag* and Ag) were allowed to compete in binding to the antibody (Ab) under conditions where Ag* much less than Ab much less than Ag. The data were analyzed according to a new theory developed for the analysis of competitive binding of two ligands to a heterogeneous receptor. The theory indicates that the binding degree of a labeled ligand measured at various concentrations of the receptor can be used to prepare a standard curve relating the binding degree of the labeled ligand and the average of the concentrations of the free receptor components which are in binding equilibrium with another unlabeled ligand. For homogeneous receptors, the method gives usual binding constants for the unlabeled ligand, but for heterogeneous receptors, it gives a new type of average binding constant for the unlabeled ligand in which the contribution of each receptor component is amplified in proportion to its affinity against the labeled ligand. This average binding constant was named the "affinity-average binding constant." A rabbit anti-blasticidin S (BLS) antiserum analyzed by the present method using beta-galactosidase-labeled BLS as the labeled ligand was found to be fairly homogeneous with respect to the affinity and to have a binding constant of 1.48 +/- 0.24 (S.D.) X 10(8) M-1 for unlabeled BLS. PMID- 3086298 TI - Effects of phenobarbital, 3-methylcholanthrene and polychlorinated biphenyls on sex-specific forms of cytochrome P-450 in liver microsomes of rats. AB - The effects of treatment with phenobarbital, 3-methylcholanthrene or polychlorinated biphenyls (PCB) on the amounts of sex-specific forms of cytochrome P-450, namely P-450-male and P-450-female, in male and female rats were studied. Although treatment with phenobarbital, 3-methylcholanthrene or PCB markedly increased the total amount of hepatic cytochrome P-450, P-450-male and P 450-female were rather decreased or not significantly changed. Thus, the percentages of P-450-male and P-450-female in the total cytochrome P-450 were decreased in liver microsomes from the treated rats. The increases in specific cytochrome P-450, such as P-448-H, P-448-L, and P-450I-c accounted for the increase in the total amount of cytochrome P-450 in the treated rats. The treatment with phenobarbital or PCB increased the activities of testosterone 16 alpha-hydroxylase, benzo(a)pyrene hydroxylase and aminopyrine N-demethylase more markedly in female rats than in male rats. Similarly, the treatment with 3 methylcholanthrene increased benzo(a)pyrene hydroxylase more markedly in female rats. Therefore, the sex-differences in testosterone 16 alpha-hydroxylase, benzo(a)pyrene hydroxylase, and aminopyrine N-demethylase activities became smaller after the drug treatment. These results indicate that sex-specific P-450 male and P-450-female were unaffected, or even depressed by the agents in some cases. PMID- 3086299 TI - Studies on T. utilis tRNATyr variants with enzymatically altered D-loop sequences. II. Relationship between the tertiary structure and tyrosine acceptance. AB - The nucleotide sequence of T. utilis tRNATyr has been modified to have a deletion or substitution of the "conserved" nucleotide sequence Gm18-G19 in the D-loop by enzymatic procedures in vitro. Conformations of the variant tRNAs were analyzed by measuring melting profiles and electrophoretic mobilities in "native" polyacrylamide gels, and by examining the RNase T1 digestion patterns in sequencing gels. The results obtained shed light on the importance of the interaction between the sequence Gm18-G19 and nucleotides in the T psi C-loop (probably psi 57-C58) for the maintenance of the total conformation of tRNATyr in solution. The association of D-loop and T psi C-loop regions in the variant tRNATyrs is slightly relaxed even at room temperature and melting occurred at temperatures higher than 40 degrees C. The relationship between the tertiary structure of the variant tRNA and its aminoacylation capacity was assayed at various temperatures. The results indicate that highly ordered tertiary structure is needed for tRNATyr to be fully aminoacylated. PMID- 3086301 TI - Quantitative analysis of mouse tyrosinase by enzyme-linked immunosorbent assay. AB - A sensitive, specific, competitive enzyme-linked immunosorbent assay (ELISA) was developed for quantitative analysis of tyrosinase. Binding sites of anti tyrosinase antibodies were competed for by purified tyrosinase adsorbed onto microtiter plates and a known (standard) or unknown (sample) amount of tyrosinase in solution. Adsorbed antibodies were detected by goat anti-rabbit IgG F(ab')2 labeled with peroxidase. A sensitivity range of 2.1 to 14 ng (30-200 fmol)/well was obtained. SDS was found to be the most suitable detergent for solubilizing the enzyme. Tyrosinase was extracted from B16 mouse melanoma and assayed by the ELISA. The tyrosinase content per mg melanoma protein was 505 +/- 106 (S.D.) ng. This assay is not only useful for measuring the content of normal tyrosinase in crude extracts but also is possibly applicable to detecting the unprocessed tyrosinases. PMID- 3086300 TI - A cDNA clone used to study mRNA inducible in human tonsillar lymphocytes by a tumor promoter. AB - A cDNA clone inducible by either a tumor promoter, 12-o-tetradecanoyl phorbol-13 acetate (TPA), or a T-cell mitogen, phytohemagglutinin (PHA), was isolated from a cDNA library constructed from the poly(A) + RNAs of TPA- and PHA-stimulated human tonsillar lymphocytes, and was named pLD78. Stimulation of the tonsillar lymphocytes with either TPA or PHA increased the amount of pLD78-specific RNA by about 10-fold, and simultaneous stimulation with TPA and PHA, by at least 30 fold. Analysis of the pLD78 cDNA sequence revealed that it codes for a polypeptide consisting of 92 amino acid residues, including a putative signal sequence. Moreover, the sequence of the 5' flanking region of the nuclear DNA encoding for the pLD78 cDNA showed a significant homology with the corresponding regions of the human interleukin 2 and immune interferon genes. PMID- 3086302 TI - Purification and characterization of yeast L-kynurenine aminotransferase with broad substrate specificity. AB - L-Kynurenine aminotransferase [L-kynurenine:2-oxoglutarate aminotransferase (cyclizing), EC 2.6.1.7] has been purified to homogeneity and crystallized from cell-free extracts of a yeast, Hansenula schneggii, grown in a medium containing L-tryptophan as an inducer. The enzyme has a molecular weight of about 100,000 and consists of two subunits identical in molecular weight (52,000). The enzyme exhibits absorption maxima at 280, 335, and 430 nm, and contains 2 mol of pyridoxal 5'-phosphate per mol of enzyme. The enzyme-bound pyridoxal 5'-phosphate shows negative circular dichroic extrema, in contrast with other pyridoxal 5' phosphate acting on L-amino acids. In addition to L-kynurenine and alpha ketoglutarate, which are the most preferred substrates, a large number of L-amino acids and alpha-keto acids can serve as substrates; the extremely broad substrate specificity is the most characteristic feature of this yeast enzyme. The enzyme activity is significantly affected by both carbonyl and sulfhydryl reagents. Certain dicarboxylic acids such as adipate and pimelate act as competitive inhibitors. Addition of various substrate amino acids to the culture medium results in the inductive formation of aminotransferases which are immunochemically indistinguishable from L-kynurenine aminotransferase. PMID- 3086303 TI - Analysis of expression of yeast enolase 1 gene containing a longer pyrimidine rich region located between the TATA box and transcription start site. AB - Yeast ENO1 promoter was prepared by a chemical synthetic method. Two variant promoters containing a pyrimidine-rich region (CT block), located between the TATA box and the transcription start site, either 32 or 34 base pairs (bp) longer than the native ENO1 promoter were isolated during the chemical synthesis. Gene expression of variant promoters was compared with that of the native promoter by measuring the amount of mRNA and the activity of beta-galactosidase by constructing ENO1-lacZ gene fusions. No significant differences were observed between the native and variant promoters in transcription levels. The start site of transcription was mapped on CAAG, a consensus sequence of transcription start site of yeast glycolytic genes. The results suggest a longer CT block in ENO1 promoter may not affect the expression of the yeast ENO1 gene. In addition, the level of ENO1 gene expression was found to be higher in stationary phase cells than in log phase cells. PMID- 3086304 TI - Purification and characterization of proteinase inhibitors from winged bean (Psophocarpus tetragonolobus (L.) DC.) seeds. AB - Seven proteinase inhibitors were isolated from winged bean seeds by ion-exchange chromatographies. These inhibitors had molecular weights of around 20,000, included four half-cystine residues, and were Kunitz-type inhibitors. Two (WTI-2 and 3) inhibited bovine trypsin strongly and four (WCI-1, 2, 3, and 4) inhibited bovine alpha-chymotrypsin, but in different ways. One mole of WCI-2 or -3 could inhibit 2 mol of alpha-chymotrypsin. The remaining inhibitor (WTCI-1) could bind both bovine trypsin and alpha-chymotrypsin at the molar ratio of 1:1, but not simultaneously. All four chymotrypsin inhibitors cross-reacted with rabbit anti WCI-3 serum, while the other inhibitors did not. PMID- 3086305 TI - Two tandemly located promoters, artificially constructed, are active in a Bacillus subtilis alpha-amylase secretion vector. AB - An 85 bp DNA fragment, the nucleotide sequence of which had 84% homology with the sequence for the promoter, ribosome binding site and NH2-terminal five amino acids of the Bacillus amyloliquefaciens alpha-amylase gene, was chemically synthesized. In order to analyze the promoter activity of a Bacillus subtilis alpha-amylase secretion vector, the fragment was inserted between the promoter and signal peptide-coding region of Bacillus subtilis alpha-amylase gene. Both promoters, tandemly repeated, functioned in transcribing the B. subtilis alpha amylase signal peptide-coding region followed by the Escherichia coli beta lactamase structural gene. The transcription initiation sites were determined by the primer extension method. The extracellular production of beta-lactamase was stimulated by two promoters as compared with that by the plasmids containing either promoter region alone. The change of two amino acids in the NH2-terminal region of the B. subtilis alpha-amylase signal peptide had no effect on the secretion of beta-lactamase from B. subtilis cells. PMID- 3086306 TI - Determination of NADPH-specific dihydropteridine reductase in extract from human, monkey, and bovine livers by single radial immunodiffusion: selective assay differentiating NADPH- and NADH-specific enzymes. AB - It has been difficult to determine exactly NADPH-specific dihydropteridine reductase [EC 1.6.99.10] in samples which also contain NADH-specific dihydropteridine reductase [EC 1.6.99.7], because the latter enzyme interferes with the activity measurement of the former. We have devised a method to measure selectively the NADPH-specific reductase in crude extracts of bovine, human and monkey livers by the single radial immunodiffusion method using specific antiserum against the enzyme. This method makes it possible to determine the enzyme amount in 5 microliters of the 3-volume extracts of the livers. The amounts of NADPH-specific dihydropteridine reductase were calculated to be 0.252, 0.296, and 0.583 munits/5 microliter of the extracts of bovine, human, and monkey livers, respectively. PMID- 3086307 TI - Aberrant composition of chondroitin sulfates in the cartilage-type proteoglycan isolated from the iliac crest of patients with some lysosomal storage diseases. AB - In order to investigate the involvement of cartilage proteoglycans in the pathogenesis of human congenital skeletal disorders, proteoglycans were extracted with 4 M guanidine HCl from the iliac crest cartilage of children with various skeletal diseases; lysosomal storage diseases (group I), osteochondrodysplasias (group II) and controls (group III). The cartilage-type proteoglycan (PG-H) was purified and its chondroitin sulfate moiety was analyzed by digestion with chondroitinase-ABC. In group II and group III, the relative amounts of the unsaturated disaccharide products changed in an age-related manner; decrease (from 50% to 30%) of delta Di-4S with a compensatory increase (from 40% to 60%) of delta Di-6S with increasing age from 0 to 15 years. On the other hand, some cases in group I showed aberrant composition of the disaccharide products; a lower content of delta Di-4S with a correspondingly higher content of delta Di 6S. Patients in group I have clinically similar skeletal disorders, and the extent of the compositional abnormality seems to reflect the severity of the skeletal disorder. Therefore, one may consider that the aberrant composition of the glycosaminoglycans in PG-H is involved in the pathogenesis of the skeletal disorder of lysosomal storage diseases. PMID- 3086308 TI - Unfolding and refolding of the constant fragment of the immunoglobulin light chain containing an intramolecular mercury bridge. AB - The conformation of the constant fragment of the immunoglobulin light chain in which the intrachain disulfide bond is replaced by the bond S-Hg-S (CL-Hg fragment), was as compact as that of the intact CL fragment, but its stability to guanidine hydrochloride was lower than that of the intact CL fragment [Goto, Y. & Hamaguchi, K. (1986) Biochemistry in press]. The kinetics of reversible unfolding and refolding of the CL-Hg fragment by guanidine hydrochloride were studied and compared with those for the intact CL and reduced CL fragments [Goto, Y. & Hamaguchi, K. (1982) J. Mol. Biol. 156, 891-910, 911-926]. The unfolding kinetics were explained on the basis of a three-species mechanism, U1----U2----F, where U1 and U2 are respectively slow-folding and fast-folding species of unfolded protein, and F is folded protein. However, an additional isomerization, though its contribution to the overall reaction process is small, had to be taken into account to explain the refolding kinetics. The kinetic properties of interconversion between U1 and U2 were similar to those for the intact CL and reduced CL fragments. This suggested that the same prolyl residue is involved in the isomerization reactions in the unfolded states of the intact CL, reduced CL, and CL-Hg fragments. The rate constant for the unfolding process, F to U2, was about 20 times greater than those for the intact CL and reduced CL fragments, while the rate constant for the refolding process, U2 to F, lay between the values for the intact CL and the reduced CL fragment. The free energy profiles of unfolding and refolding of the intact CL, reduced CL, and CL-Hg fragments were compared. PMID- 3086309 TI - Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P 450 monooxygenase induced by barbiturates in Bacillus megaterium. AB - A unique cytochrome P-450-dependent fatty acid monooxygenase from Bacillus megaterium ATCC 14581 is strongly induced by phenobarbital (Narhi, L. O., and Fulco, A. J. (1982) J. Biol. Chem. 257, 2147-2150) and many other barbiturates (Kim, B.-H., and Fulco, A. J. (1983) Biochem. Biophys. Res. Commun. 116, 843 850). This monooxygenase has now been purified to homogeneity from pentobarbital induced bacteria as a single polypeptide with a molecular weight of 119,000 +/- 5,000 daltons. In the presence of NADPH and O2, it can catalyze the oxygenation of long chain fatty acids without the aid of any other protein. The enzyme has a catalytic center activity of 4,600 nmol of fatty acid oxygenated per nmol of P 450 (the highest activity yet reported for a P-450-dependent monooxygenase) and also functions as a highly active cytochrome c reductase in the presence of NADPH. The purified holoenzyme is a soluble protein containing 40 mol % hydrophobic amino acid residues and 1 mol each of FAD and FMN/mol of heme. It is isolated and purified in the low spin form but is converted to the high spin form in the presence of long chain fatty acids. The enzyme, which catalyzes the omega 2 hydroxylation of saturated fatty acids and the hydroxylation and epoxidation of unsaturated fatty acids has its highest affinity (Km = 2 +/- 1 microM) for the C15 and C16 chain lengths. PMID- 3086311 TI - The influence of bound GDP on the kinetics of guanine nucleotide binding to G proteins. AB - Purified guanine nucleotide-binding regulatory proteins, as either the oligomers or the isolated nucleotide-binding alpha subunits, display anomalous kinetics of nucleotide binding. This is due to the presence of tightly bound GDP in these preparations. The dissociation of bound GDP is the rate-limiting step for nucleotide binding. GDP can be removed by chromatography in the presence of 1 M (NH4)2SO4 and 20% glycerol, which yields preparations of G proteins that contain less than 0.1 mol of GDP/mol of guanosine 5'-(gamma-thio)triphosphate (GTP gamma S)-binding site. When the GDP is removed, the binding of GTP gamma S displays kinetics consistent with a bimolecular reaction. PMID- 3086310 TI - Evidence for a guanine nucleotide-binding regulatory protein in invertebrate and mammalian sperm. Identification by islet-activating protein-catalyzed ADP ribosylation and immunochemical methods. AB - The abalone sperm adenylate cyclase does not appear to be regulated by guanine nucleotides, but has a Mg2+-supported catalytic activity similar to other hormone and guanine nucleotide-regulated enzymes (Kopf, G. S., and Vacquier, V. D. (1984) J. Biol. Chem. 259, 7590-7596; Kopf, G. S., and Vacquier, V. D. (1985) Biol. Reprod. 33, 1094-1104). The present studies were undertaken to ascertain whether the abalone enzyme has associated guanine nucleotide-binding regulatory proteins. Membrane fractions were incubated with either islet-activating protein (IAP) or cholera toxin and analyzed by sodium dodecyl sulfate SDS-polyacrylamide gel electrophoresis for the presence of toxin-catalyzed ADP-ribosylated proteins. The supernatant from a Lubrol PX-extracted 48,000 X g pellet fraction contained a Mr = 41,000 IAP substrate. This substrate could not be ADP-ribosylated prior to detergent extraction. Lubrol PX-solubilized fractions of membrane preparations from mouse, bovine, and human sperm also contained a Mr = 41,000 IAP substrate. These proteins co-migrated on sodium dodecyl sulfate-polyacrylamide gels with the Mr = 41,000 alpha i-subunit of the inhibitory guanine nucleotide-binding regulatory protein (Gi) from transformed chicken embryo fibroblast and mouse S-49 lymphoma membrane extracts. The sperm IAP substrates displayed similar protease digest patterns to alpha i of mouse S-49 lymphoma cells. Sea urchin sperm analyzed in a similar manner contained a Mr = 39,000 IAP substrate. Cholera toxin catalyzed ADP-ribosylation of specific sperm membrane proteins was not observed in any of the sperm preparations tested. The presence of the beta-subunit common to both the stimulatory and inhibitory guanine nucleotide-binding regulatory heterotrimers was confirmed in sperm using an antiserum directed against the purified beta-subunit of the guanine nucleotide-binding regulatory proteins from bovine brain. It is concluded that all of the sperm tested, with the possible exception of sea urchin sperm, contain a Gi-like protein. Additional properties of these proteins and their role(s) in sperm function are currently being examined. PMID- 3086312 TI - Isolation and properties of a phosphatidylcholine-specific phospholipase C from bull seminal plasma. AB - A phospholipase C which hydrolyzes [14C]phosphatidylcholine has been purified 1782-fold from 70% ammonium sulfate extract of bull seminal plasma. Purification steps included acid precipitation, chromatography on DEAE-Sephacel, concanavalin A, octyl-Sepharose 4B and Ultrogel AcA 34. The final step provided homogeneous phospholipase C as determined by polyacrylamide gel electrophoresis. The enzyme comprised two subunits, Mr 69,000 and Mr 55,000, respectively. The enzyme had an optimum at pH 7.2 and pI 5.0. EDTA, Cd2+, Pb2+, Ni2+, Fe2+, and Zn2+ inhibited phospholipase C activity. Km and Vmax on p-nitrophenyl phosphorylcholine and phosphatidylcholine substrates were 20 mM and 17 mumol/min/mg of the purified enzyme and 100 microM and 18 mumol/min/mg of the purified enzyme, respectively. The enzyme appeared to be localized in the acrosome as judged by the binding of anti-phospholipase C to the acrosome. This phospholipase C, unlike other known phospholipases (C), did not hydrolyze [1-14C]phosphatidylinositol. The testicular extract of the guinea pig contained inactive phospholipase C which was activated on incubation with acrosin and trypsin but not chymotrypsin. PMID- 3086313 TI - Plasminogen activator inhibitor from human fibrosarcoma cells binds urokinase type plasminogen activator, but not its proenzyme. AB - An approximately 75% pure form of a human Mr approximately 54,000 plasminogen activator inhibitor from conditioned culture fluid of the fibrosarcoma cell line HT-1080 was obtained by a single step of chromatography on concanavalin A Sepharose. The inhibitor inhibited human urokinase-type plasminogen activator (u PA) and tissue-type plasminogen activator, but not plasmin. Rabbit antibodies against this plasminogen activator inhibitor also reacted with a plasminogen activator inhibitor with identical electrophoretic mobility in extracts of human blood platelets, indicating that the HT-1080-inhibitor is of the same type as the inhibitor of blood platelets. As revealed by sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by fibrin-agarose zymography, incubation of HT-1080-inhibitor with the active form of human u-PA led to the formation of an equimolar sodium dodecyl sulfate-resistant complex between them; in contrast, no complex formation was observed between the inhibitor and the proenzyme form of human u-PA (pro-u-PA). Likewise, using a column of anti inhibitor antibodies coupled to Sepharose for removal of excess inhibitor and activator-inhibitor complexes, the potential enzymatic activity of pro-u-PA was found to be unaffected by incubation with inhibitor under conditions in which more than 95% of the active u-PA had formed complex with inhibitor. PMID- 3086314 TI - An analysis of the structure of the product of the rbsA gene of Escherichia coli K12. AB - The predicted amino acid sequence of rbsA, a gene from the high affinity ribose transport operon (rbs) of Escherichia coli K12, is homologous to the products of hisP, malK, and pstB, components of the histidine, maltose, and phosphate high affinity transport operons. The recent finding by Hobson et al. (Hobson, A. C., Weatherwax, R., and Ames, G.F.-L. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 7333 7337) that the hisP and malK products bind ATP suggests that these four gene products may be involved in coupling the energy from ATP to drive the active transport in their respective transport systems. Each gene product contains a sequence of glycine and basic residues which are characteristic of an ATP-binding site (Walker, J.E., Saraste, M., Runswick, M.J., and Gay, N.J. (1982) EMBO J. 1, 945-951). Interestingly the N- and C-terminal halves of rbsA are also homologous, suggesting that a primordial gene duplication and subsequent fusion of the products occurred. PMID- 3086315 TI - Unusual sensitivity of cytosolic free Ca2+ to changes in extracellular Ca2+ in rat C-cells. AB - An essential function of C-cells is to monitor extracellular Ca2+ concentration ([Ca2+]e) and to respond to changes in [Ca2+]e by regulating hormone secretion. Using the calcitonin-secreting rat C-cell line rMTC 44-2, we have investigated a possible tight linkage between [Ca2+]e and cytosolic free Ca2+ ([Ca/+]i). We have demonstrated, using the Ca2+ indicator Quin 2, that the [Ca2+]i is particularly sensitive to changes in [Ca2+]e. Sequential increases in [Ca2+]e as small as 0.1 mM evoke clear elevations in [Ca2+]i. In contrast, other cell types tested did not alter their [Ca2+]i in response to increasing [Ca2+]e even to levels as high as 4.0 mM. Sequential 1.0 mM increments in [Ca2+]e caused the [Ca2+]i to rise from a base line of 357 +/- 20 nM Ca2+i at 1.0 mM Ca2+e to a maximum of 1066 +/- 149 nM Ca2+i at 5.0 mM Ca2+e. [Ca2+]e above 2.0 mM produced a biphasic response in [Ca2+]i consisting of an immediate (less than 5 s) spike followed by a decay to a new plateau. Treatment of rMTC 44-2 cells with either 50 mM K+ or 100 nM ionomycin at 1.0 mM Ca2+e caused an immediate spike in [Ca2+]i to micromolar levels. Pretreatment with EGTA or verapamil inhibited completely the increase in [Ca2+]i induced by 50 mM K+. However, pretreatment with EGTA only slightly attenuated the spike phase in [Ca2+]i produced by ionomycin, demonstrating that ionomycin released intracellular stores of calcium. We conclude that rMTC 44-2 cells regulate [Ca2+]i by monitoring small physiological changes in [Ca2+]e, the primary secretagogue for C-cells. PMID- 3086316 TI - Protein kinase-mediated activation of temperature-labile and temperature-stable cholesteryl ester hydrolases in the rat testis. AB - Both temperature-stable and temperature-labile testicular cholesteryl ester hydrolases are shown to be regulated by an endogenous cAMP-dependent protein kinase activity. The temperature-stable form (Mr = 28,000) was activated 3-fold by the endogenous kinase. This activation was completely blocked by protein kinase inhibitor. Following purification by high performance gel permeation chromatography, the temperature-stable form could also be activated 2-fold by bovine heart protein kinase, type I. The partially purified endogenous protein kinase, type I, which was completely separated from hydrolase activity by ion exchange chromatography, increased hydrolase activity 2-fold in the presence of optimal concentrations of cAMP, ATP, and Mg2+. Cholesteryl ester hydrolase activity could be stabilized indefinitely at -10 degrees C with the addition of 0.1 mM thioglycolate, but not by other thiol reagents. In contrast, the endogenous protein kinase activity was lost from 104,000 X g supernatants after 14 days. However, the property of activation could be restored by addition of bovine heart protein kinase. The temperature-labile hydrolase (Mr = 72,000) could be totally inactivated by a Mg2+-dependent, fluoride-sensitive cytosolic factor and reactivated by cAMP-dependent protein kinase. These observations strongly suggest that the inactivating factor is a phosphoprotein phosphatase. PMID- 3086317 TI - Genetic mapping of the chromosome of the cyanobacterium, Anabaena variabilis. Proximity of the structural genes for nitrogenase and ribulose-bisphosphate carboxylase. AB - A cosmid library of DNA from the chromosome of the nitrogen-fixing cyanobacterium, Anabaena variabilis, has been organized into about 40 linkage groups on the basis of cosmid-cosmid hybridization. Nitrogenase and ribulose bisphosphate carboxylase are protein complexes that are, respectively, active in heterocysts and absent from vegetative cells, and active in vegetative cells and absent from heterocysts. The structural genes for the proteins of these two complexes are found to be in close proximity within one of the linkage groups. Other genes have also been tentatively localized on the basis of heterologous hybridization. Possible methods for linking the defined linkage groups are discussed. PMID- 3086318 TI - Remodeling of arachidonate-containing phosphoglycerides within the human neutrophil. AB - Initial incorporation and subsequent remodeling of 16 phosphoglyceride molecular species containing arachidonate in the human neutrophil have been studied. Neutrophils were pulse-labeled with [3H]arachidonic acid (AA) for 5 min, then phospholipids were analyzed either at this time point or after a subsequent 120 min incubation. [3H]AA was found to be incorporated into phosphoglycerides phosphatidylinositol (PI) greater than phosphatidylcholine (PC) greater than phosphatidylethanolamine (PE) by 5 min. Incorporation of [3H]AA was not related to pool size, but reflected an increase in phosphoglyceride turnover. Following the 120-min incubation, only PE gained a significant amount of labeled arachidonate. Specific activity analysis revealed that PI contained the highest labeled/unlabeled ratio at both 5 min and 120 min. After the initial 5-min pulse, the majority of [3H]arachidonate was incorporated into 1-acyl-2-[3H]arachidonoyl sn-glycero-3-PC, -PE, and -PI showing no preference for fatty acyl chains at the sn-1 position. However, [3H]AA was remodeled into 1-alkyl-acyl-and 1-alk-1-enyl acyl-sn-glycero-3-PC and -PE molecular species in those neutrophils incubated for the additional 120 min. Specific activities of [3H]AA within all diacyl molecular species were initially higher relative to those alkyl-acyl and alk-1-enyl-acyl molecular species, but for PC and PE became more uniform as label shifted into ether and plasmalogen pools during the additional 120-min incubation. In contrast, the specific activity of 1-stearoyl-2-arachidonoyl-sn-glycero-3-PI remained constant throughout the 120-min incubation. PMID- 3086319 TI - Preparation and characterization of FAD-dependent NADPH-cytochrome P-450 reductase. AB - NADPH-cytochrome P-450 reductase releases FAD upon dilution into slightly acidic potassium bromide. Chromatography on high performance hydroxylapatite resolved the FAD-dependent reductase from holoreductase. The FAD dependence was matched by a low FAD content, with the ratio of FAD to FMN as low as 0.015. The aporeductase had negligible activity toward cytochrome c, ferricyanide, menadione, dichlorophenolindophenol, nitro blue tetrazolium, and an analogue of NADP, acetylpyridine adenine dinucleotide phosphate. A 4-min incubation in FAD reconstituted from one-half to all of the enzyme activity, as compared to the untreated reductase, depending upon the substrate. After a 2-h reconstitution, the reductase eluted from hydroxylapatite at the same location in the elution profile as did the untreated holoreductase. The reconstituted reductase had little flavin dependence, was nearly equimolar in FMN and FAD, and had close to the specific activity, per mol of flavin, of untreated reductase. The dependence upon FAD implies that FMN is not a competent electron acceptor from NADPH. Thus, the FAD site must be the only point of electron uptake from NADPH. PMID- 3086320 TI - The protein cofactor necessary for ADP-ribosylation of Gs by cholera toxin is itself a GTP binding protein. AB - A membrane-bound protein cofactor (ARF) is required for the cholera toxin dependent ADP-ribosylation of the stimulatory regulatory component (Gs) of adenylate cyclase. Improved methods for the purification of ARF from bovine brain are described. ARF has a high-affinity binding site for guanine nucleotides. Binding of GTP or GTP gamma S to ARF is necessary for the activity of the cofactor; GDP X ARF does not support ADP-ribosylation of Gs. Although the protein as purified contains stoichiometric amounts of GDP, GTPase activity of isolated ARF was not detected. Cholera toxin-dependent activation of adenylate cyclase thus requires two guanine nucleotide binding proteins. PMID- 3086321 TI - Monoclonal antibodies to bovine UDP-galactosyltransferase. Characterization, cross-reactivity, and utilization as structural probes. AB - A series of mouse monoclonal antibodies has been developed against a soluble form of bovine UDP-galactose:N-acetylglucosamine galactosyltransferase purified to apparent chemical homogeneity by a combination of affinity and immunoadsorption chromatography. The purified enzyme consists of two molecular mass variants of 42 and 48 kDa. Individual monoclonal antibodies were selected for by their ability to recognize immobilized affinity-purified galactosyltransferase and were not reactive against bovine alpha-lactalbumin and bovine immunoglobulins. Based on competitive binding assays and Western blot analysis with either galactosyltransferase or lactose synthetase (covalently cross-linked alpha lactalbumin galactosyltransferase), these monoclonal antibodies can be subdivided into four groups. Group A (3 clones) recognize an epitope at or near the alpha lactalbumin binding site. In addition, this group is cross-reactive with soluble galactosyltransferase from human milk and pleural effusion. Group B (6 clones) and D (1 clone) appear to recognize two different epitopes on the 6-kDa fragment which is released when the 48-kDa galactosyltransferase polypeptide is converted to the 42-kDa form, apparently by proteolysis. Groups A and C (1 clone) recognize epitopes found on both the 48- and 42-kDa polypeptide. Interestingly, immunofluorescence studies indicate that only two monoclonal antibody groups (C and D) are able to decorate membrane-bound galactosyltransferase (Golgi associated) in formalin-fixed, methanol-, or detergent-permeabilized cells. Thus, these groups of monoclonal antibodies appear to identify four separate structural/functional domains on soluble galactosyltransferase, two of which are not readily accessible for binding in situ. PMID- 3086322 TI - Purification of arachidonate 5-lipoxygenase from porcine leukocytes and its reactivity with hydroperoxyeicosatetraenoic acids. AB - Arachidonate 5-lipoxygenase was purified to near homogeneity from the 105,000 X g supernatant of porcine leukocyte homogenate by immunoaffinity chromatography using a monoclonal anti-5-lipoxygenase antibody. Reaction of the purified enzyme with arachidonic acid produced predominantly 5-hydroperoxy-6,8,11,14 eicosatetraenoic acid with concomitant formation of several more polar compounds in smaller amounts. These minor products were identified as the degradation products of leukotriene A4, namely, 6-trans-leukotriene B4 (epimeric at C-12) and an epimeric mixture of 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acids. These compounds were also produced by reaction of the enzyme with 5-hydroperoxy eicosatetraenoic acid. Association of the 5-lipoxygenase and leukotriene A synthase activities was demonstrated by several experiments: heat inactivation of enzyme, effect of selective 5-lipoxygenase inhibitors, requirements of calcium ion and ATP, and self-catalyzed inactivation of enzyme. The enzyme was also active with 12- and 15-hydroperoxy-eicosatetraenoic acids producing (5S,12S)- and (5S,15S)-dihydroperoxy acids, respectively. Maximal velocities of the reactions with these hydroperoxy acids as compared with that of arachidonic acid (100%, 0.6 mumol/3 min/mg of protein) were as follows: 5-hydroperoxy acid, 3.5%, 12 hydroperoxy acid, 22%, and 15-hydroperoxy acid, 30%. PMID- 3086323 TI - The subcellular distribution of terminal N-acetylglucosamine moieties. Localization of a novel protein-saccharide linkage, O-linked GlcNAc. AB - Previously our laboratory reported the discovery of a novel protein-saccharide linkage in which single N-acetylglucosamine (GlcNAc) residues are attached in O linkages to protein (Torres, C. R., and Hart, G. W. (1984) J. Biol. Chem. 259, 3308-3317). This linkage was first found on plasma membrane proteins of living cells by galactosylation with bovine milk galactosyltransferase. Here we report the distribution of O-linked GlcNAc in highly enriched rat liver subcellular organelles. Nonidet P-40 solubilized organelles were labeled by galactosyltransferase with UDP-[3H]galactose, and the amount of radiolabel occurring on GlcNAc residues in O-linkages was assessed by its sensitivity to beta-elimination and by its resistance to deglycosylation with endo-beta-N acetylglucosaminidase F. The presence of galactose-labeled O-linked GlcNAc residues was confirmed by high voltage paper electrophoresis. There is a 17-fold range per mg of protein in the amount of galactosylatable terminal GlcNAc residues found in the various organelles, as well as a wide range in the organelles' apparent content of O-linked GlcNAc residues. Nuclei and the soluble fraction of rat liver cells are particularly enriched with proteins bearing O linked GlcNAc residues, although these residues are demonstrable in virtually all organelles tested. Furthermore, examination by sodium dodecyl sulfate polyacrylamide gel electrophoresis reveals that many different organelle-specific proteins are glycosylated with O-linked GlcNAc residues. Because of the wide occurrence of this unique linkage, these data suggest that glycosylation with O linked GlcNAc residues is not an exclusive marker for a particular organelle. In addition, we have surveyed the organelles for their content of glycoproteins bearing GlcNAc-terminated N-linked oligosaccharides. Our data demonstrate that there are significant amounts of these oligosaccharides in rough and stripped microsomes, nuclei, and nuclear envelopes. In light of evidence that terminal GlcNAc transferases are localized to the Golgi complex, these data suggest that there are glycoproteins which enter into the Golgi for processing and then are transported back into the rough endoplasmic reticulum, and possibly the nucleus. PMID- 3086324 TI - A microtubule-associated protein in Drosophila melanogaster: identification, characterization, and isolation of coding sequences. AB - Microtubules and microtubule-associated proteins (MAPs) have been isolated from cultured cells of Drosophila melanogaster by a taxol-dependent polymerization procedure. The principal MAPs are a group of four polypeptides with similar electrophoretic mobilities corresponding to approximately Mr 205,000 (the 205K MAP). These proteins are resistant to precipitation by boiling. One mouse monoclonal antibody and one polyclonal rabbit antiserum specific for the Mr 205,000 MAP were produced and characterized by immunoblotting and indirect immunofluorescence. Both antibody preparations stain the Mr 205,000 molecules and an Mr 255,000 molecule in immunoblots of Drosophila cell homogenates; the rabbit antiserum also stains an Mr 150,000 triplet. Both preparations stain the microtubules of the mitotic spindle, and the rabbit antiserum stains the cytoplasmic microtubules as well. Experiments using affinity-purified rabbit antiserum demonstrate that it is the Mr 205,000 species that is located in the mitotic apparatus and on cytoplasmic microtubules. A random shear genomic library was produced in the expressing vector lambda gt11 and screened with the rabbit antiserum to isolate the DNA sequences encoding these polypeptides. Several cross hybridizing clones were recovered, shown to encode antigenic determinants in the Mr 205,000 MAP, and characterized by hybridization to Northern blots of mRNA and Southern blots of genomic DNA. Analysis by in situ hybridization reveals that the gene encoding the 205K MAP is located in polytene region 100EF. PMID- 3086326 TI - In vitro expression of a 38,000 dalton heparin-binding glycoprotein by morphologically differentiated smooth muscle cells. AB - In vitro, high density monolayer cultures of vascular smooth muscle cells can be induced to form multicellular nodules. The nodular cells appear to be morphologically differentiated smooth muscle cells. Sodium dodecyl sulfate (NaDodSO4)-polyacrylamide gel electrophoresis was used to compare the proteins synthesized and secreted by monolayer and nodular cultures of smooth muscle cells. Although most proteins appeared to be similar, the nodular cultures contained a unique heparin binding protein of Mr = 38,000 (38kD protein) (Millis, A.J.T., Hoyle, M., Reich, E., and Mann, D.M., 1985, J. Biol. Chem., 260:3754 3761). The 38kD protein was glycosylated and its apparent molecular weight was shifted to Mr = 32,500 after synthesis in the presence of tunicamycin or digestion with endoglycosidase F. The production of 38kD protein by nodular cell cultures did not appear to result from the degradation of a high molecular weight precursor in nodular conditioned medium. Further, it was not detected in monolayer cell conditioned medium that had been incubated with nodular cells. Finally, its synthesis was not induced in monolayer cell cultures that had been labeled in nodular cell conditioned medium. The 38kD protein appears to be uniquely associated with nodular cultures of smooth muscle cells. PMID- 3086325 TI - Schwann cell myelination: induction by exogenous basement membrane-like extracellular matrix. AB - Exposing rat Schwann cells co-cultured with nerve cells to a reconstituted basement membrane induced the formation of myelin segments by Schwann cells. This occurred in a serum-free culture medium in which, in the absence of this matrix, Schwann cells proliferate but fail to differentiate. This reconstituted basement membrane was prepared from solubilized extracellular matrix proteins synthesized by a basement membrane-producing murine tumor. The major constituents of this reconstituted matrix are collagen type IV, laminin, heparan sulfate proteoglycan, entactin, and nidogen. The matrix also elicited striking morphological changes in Schwann cells, inducing them to spread longitudinally along the nerve fibers (a necessary early step in the process of ensheathment of nerve fibers). Several observations indicated that the effect of the matrix was exerted directly on Schwann cells and not indirectly through an effect on nerve cells. First, the matrix-induced cell spreading occurred only in areas in which Schwann cells directly contacted the matrix; Schwann cells that were associated with the same nerve fibers but that did not themselves directly contact the matrix did not exhibit spreading. Second, the matrix-induced alteration in Schwann cell morphology was observed in cultures in which the nerve cells were removed. These results provide direct evidence that basement membrane contact induces normal Schwann cell differentiation, and support the idea that Schwann cell differentiation in vivo may be regulated by the appearance of the basement membrane, which normally envelops terminally differentiating Schwann cells. PMID- 3086327 TI - Interleukin 3 and cell cycle progression. AB - Interleukin 3 (IL-3) is a regulatory glycoprotein required for the proliferation and differentiation of cells from many if not all hemopoietic lineages. With the emergence of the competence-progression model of cell proliferation, which predicts that growth factors function at specific stages of the cell cycle, we examined the possibility that IL-3 functions at a specific stage of the cell cycle. C-63 cells were developed as a cell line from normal murine bone marrow. They have a mast cell phenotype and require pokeweed-stimulated spleen cell conditioned medium (CM), a rich source of IL-3, for their continued growth. Exponentially growing cells were transferred from growth medium, which contains CM, to medium lacking CM or IL-3. After 24 hours, cell viability had decreased 40 50%. The remaining viable cells did not incorporate 3H-thymidine, and displayed a single peak at G1 in a DNA histogram. Restimulation of these cells with CM or IL 3 resulted in a dramatic rise in 3H-thymidine uptake 20-24 hours after restimulation. DNA histograms of restimulated cultures indicated that the cells were progressing in a wave-like fashion throughout the remainder of the cell cycle. The length of time necessary for cells to be in contact with CM or IL-3 before they could progress into the remainder of the cell cycle was also examined. Cells incubated with CM or IL-3 for less than 16 hours could not progress into S phase, whereas cells incubated for 16 hours or longer could progress into S phase and through the remainder of the cell cycle. These data suggest that IL-3 exerts its function at a specific stage of the cell cycle. PMID- 3086329 TI - Isolation and characterization of nuclear lamina from Ehrlich ascites tumor cells. AB - We have developed a simple and rapid method for isolation of purified nuclear lamina from Ehrlich ascites tumor cells. The procedure employs chromatin structures prepared from whole cells at low ionic strength and is carried out under conditions that minimize the formation of artifactual protein-DNA complexes. When the isolation is performed in the presence of EDTA, nuclear lamina without distinct pore complexes is obtained. In the absence of EDTA, intact pore complexes and a large amount of vimentin 100 A filaments are seen associated with nuclear lamina. The main nuclear lamina proteins are characterized using gel electrophoresis, immunoblotting, and two-dimensional peptide mapping. An extensive structural homology is found between lamin A and lamin C, whose peptide maps differ by only one major spot, whereas lamin B has apparently unrelated pattern. PMID- 3086328 TI - Substrate utilization for lactate and energy production by heat-shocked L929 cells. AB - The hypothesis that heat shock protein (HSP) induction depends on inhibition of respiration was tested by examining the effects of heat shock on tricarboxylic acid (TCA) cycle function. In control L929 cell cultures, glucose and exogenous pyruvate were converted primarily to lactate, and glutamine was extensively oxidized, accounting for more than one-half of the calculated ATP production. During heat shock at 42 degrees C, lactate production from all of the labeled substrates and total unlabeled lactate production increased significantly while oxygen consumption increased slightly. TCA cycle oxidation of pyruvate decreased during this period while that of glutamine increased. Uncoupling of oxidative phosphorylation caused large increases in oxygen consumption at both 37 degrees C and 42 degrees C, indicating that the capacity of the respiratory chain is not exceeded during heat shock. The net effect of these alterations in substrate utilization were decreased ATP generation and increased NADH utilization. Both 14CO2 and lactate production declined during the 24-h period after cultures were returned to 37 degrees C. On the basis of these data, we conclude that while inhibition of respiration plays no apparent role, other metabolic consequences of heat shock related to energy metabolism may be involved in HSP induction. PMID- 3086330 TI - Delayed treatment with nimodipine improves cerebral blood flow after complete cerebral ischemia in the dog. AB - Ten minutes of complete cerebral ischemia was produced in 18 dogs by temporary ligation of the aorta and venae cavae. Dogs were randomly assigned to one of three groups. A bolus dose of 10 micrograms kg-1 nimodipine, a dihydropyridine calcium entry blocker, followed by a constant infusion of 1 microgram kg-1 min-1 was given at 15, 30, or 60 min post ischemia. Cerebral blood flow and metabolism were measured for 2 h postischemia. Delayed treatment with nimodipine ameliorated or reversed the cerebral hypoperfusion that routinely occurs after complete ischemia. In the groups treated at 15 and 30 min, CBF remained above 60 ml min-1 100 g-1. In the group treated at 60 min, there was a progressive decline in CBF to 37 ml min-1 100 g-1. Following treatment with nimodipine, CBF immediately increased and was maintained above 50 ml min-1 100 g-1 for the remainder of the study. Once treatment with nimodipine was begun, CBF was approximately double that of an untreated group. Changes in CBF reflected changes in cerebrovascular resistance. Nimodipine had no effect on cerebral metabolism. Since the postischemic hypoperfusion state is believed to contribute to the ultimate neurologic damage following complete ischemia, treatment with nimodipine, even if delayed up to 60 min, may improve the outcome. PMID- 3086332 TI - Sick euthyroid syndrome. PMID- 3086331 TI - Brain luxury perfusion during cardiopulmonary bypass in humans. A study of the cerebral blood flow response to changes in CO2, O2, and blood pressure. AB - CBF and related parameters were studied in 68 patients before, during, and following cardiopulmonary bypass. CBF was measured using the intraarterial 133Xe injection method. The extracorporeal circuit was nonpulsatile with a bubble oxygenator administering 3-5% CO2 in the main group of hypercapnic patients (n = 59) and no CO2 in a second group of hypocapnic patients. In the hypercapnic patients, marked changes in CBF occurred during bypass. Evidence was found of a brain luxury perfusion that could not be related to the effect of CO2 per se. Mean CBF was 29 ml/100 g/min just before bypass, 49 ml/100 g/min at steady-state hypothermia (27 degrees C), reached a maximum of 73 ml/100 g/min during the rewarming phase (32 degrees C), fell to 56 ml/100 g/min at steady-state normothermic bypass (37 degrees C), and was 48 ml/100 g/min shortly after bypass was stopped. Addition of CO2 evoked systemic vasodilation with low blood pressure and a rebound hyperemia. The hypocapnic group responded more physiologically to the induced changes in hematocrit (Htc) and temperature, CBF being 25, 23, 25, 34, and 35 ml/100 g/min, respectively, during the five corresponding periods. Carbon dioxide was an important regulator of CBF during all phases of cardiac surgery, the responsiveness of CBF being approximately 4% for each 1-mm Hg change of PaCO2. The level of MABP was important for the CO2 response. At low blood pressure states, the CBF responsiveness to changes in PaCO2 was almost abolished. An optimal level of PaCO2 during hypothermic bypass of approximately 25 mm Hg (at actual temperature) is recommended. A normal autoregulatory response of CBF to changes in blood pressure was found during and following bypass. The lower limit of autoregulation was at pressure levels of approximately 50-60 mm Hg. CBF autoregulation was almost abolished at PaCO2 levels of greater than 50 mm Hg. The degree of hemodilution neither affected the CO2 response nor impaired CBF autoregulation, although, as would be expected, it influenced CBF: In 33 women CBF was 55 ml/100 g/min at an Htc of 24%, as compared with 42 ml/100 g/min in 35 men (Htc = 28%). High PaO2 was a vasoconstrictor, the autoregulatory plateau being narrowed. The lower limit of autoregulation was shifted to a higher pressure when PaO2 was low. PMID- 3086333 TI - Pills + hostility: Rx for drug dependency. PMID- 3086334 TI - Surgery and the management of heart failure. PMID- 3086335 TI - 'Liberator of surgery from shackles of sepsis'. PMID- 3086336 TI - Somatoform disorders. Symptoms and psychiatric implications. PMID- 3086337 TI - A healthy young woman in respiratory distress. PMID- 3086338 TI - The bypass on the way to the bypass. PMID- 3086339 TI - Heat-induced illness. PMID- 3086340 TI - Autoimmune chronic active hepatitis. PMID- 3086341 TI - Nine months of diarrhea after a Mexican meal. PMID- 3086342 TI - A 64-year-old man with a 40-year-old wound. PMID- 3086343 TI - Wide-complex tachycardia after a suicide attempt. PMID- 3086344 TI - Update on strategies in mechanical ventilation. PMID- 3086345 TI - A nonagenarian who had everything. PMID- 3086346 TI - Hematologic malignancies: adult acute leukemia. PMID- 3086347 TI - Gel chromatography of pyridoxalated and glutaraldehyde-treated human haemoglobin on Superose 12. PMID- 3086348 TI - Rapid identification of NH2-terminal myristyl peptides by reversed-phase high performance liquid chromatography. AB - NH2-terminal myristyl peptides in mixtures of other peptides having the NH2 terminal blocked with acetyl, formyl or pyroglutamyl groups were selectively determined by high-performance liquid chromatography using a poly(vinyl alcohol) resin column eluted with 50 mM sodium hydrogen carbonate, pH 8.3, and a linear gradient of acetonitrile. This method was applied to the analysis of an NH2 terminal blocked peptide from a peptic digest of the catalytic subunit of adenosine 3':5'-phosphate-dependent protein kinase type II from bovine heart, showing that the peptide has a sequence myristyl-Gly-Asn-Ala. PMID- 3086349 TI - Quantitative analysis of fatty acid methyl esters and dimethyl acetals on a polar (free fatty acid phase) capillary column. AB - Separation of fatty acid methyl esters and dimethyl acetals from complex biological samples has been achieved by gas-liquid chromatography on a capillary column coated with free fatty acid phase. Response-correcting factors were determined, showing rather large variations with fatty acid length. Polyunsaturated fatty acid methyl esters were shown to have lower responses than saturated species, whereas dimethyl acetals and equivalent methyl esters were found to give similar responses. Total fatty acid and aldehyde compositions of human and simian erythrocytes were determined and compared, showing a somewhat higher level of linoleate and arachidonate, and a lower level of plasmalogens in simian erythrocytes. PMID- 3086350 TI - Affinity precipitation of proteins using bis-dyes. AB - Based on the principle of affinity precipitation of nucleotide-dependent enzymes using bis-NAD (Mosbach), Lowe et al. have recently mentioned the possibility of synthesising bis-dyes for similar applications. In this paper we report preliminary results obtained using bis-dyes in the sulphonamide form got through carbodiimide condensation of the monomer and its aminohexyl derivative for affinity precipitation. The dimer exhibited considerable selectivity for lactate dehydrogenase (90% yield). Bovine serum albumin gave a lower yield of 50% and as expected chymosin could not be precipitated by the dimer. PMID- 3086351 TI - [Immobilization of enzymatic inhibitors for the isolation of reversible immunologic sensors]. AB - The authors propose the use of specific sensors immobilized by ligands onto artificial supports, and the elaboration of a computerized system for the determination of various antigens, haptens or antibodies in biological fluids according to enzyme-linked immunosorbent assay techniques. Two enzymes are applied in this technique: the first (ribonuclease) for reversibly linking the immunocomplex to the insoluble support via disulphur bridges; the second (beta-D glucose oxidase) for labelling the antigen. Enzyme activity is measured in the presence of glucose oxidase by fixing the immunocomplex onto a pO2 electrode. After incubation of the antigen labelled with glucose oxidase and the free antigen with specific antibodies linked with ribonuclease, to reduce the pre established concentration, the reaction medium is introduced into the continuous flow cell. O2 consumption due to the enzyme reaction is measured by the actual time that the electrode is in contact with a glucose standard solution. Cleavage of the disulphur bridges is caused by an injection of dithiothreitol solution. Treatment of the signal obtained is realized with an automatic microcomputer system. The preliminary results show that reproducibility with the same membrane for ten measurements is less than 5%. Elution performed using dithiothreitol for example, shows that cleavage between the immunocomplex and the thiol-containing support is obtained after a few minutes, and 98% of the immunocomplex is eluted. PMID- 3086352 TI - New support for the large-scale purification of proteins. AB - We propose a new affinity sorbent, matrix-linked histidine, for the large-scale purification of proteins. A variety of proteins and certain peptides, each distinct from the other, were purified. Immunoglobulin G from human placenta was chosen for a detailed study concerning the effects of coupling, spacer-arm and other parameters. Multiple interactions such as charge-transfer and other ionic reactions have been suggested to be responsible for the interactions between proteins and ligand. PMID- 3086353 TI - Separation of human pepsin and gastricsin by affinity chromatography with an immobilized synthetic inhibitor. AB - Pepsin and gastricsin from human gastric juice were separated by affinity chromatography on Sepharose 4B containing the immobilized synthetic inhibitor of aspartic proteinases, Val-D-Leu-Pro-Phe-Phe-Val-D-Leu. These enzymes were bound to the support at low pH, and gastricsin was released at the same pH with buffer containing 20% dioxan. Pepsin was not released under these conditions, but was eluted at higher pH with buffer also containing 20% dioxan. To obtain perfect separations, it is recommended to use diluted samples. Proteinases from the homogenate of human gastric mucosa are isolated on DEAE-cellulose before separation by affinity chromatography. Pepsin and gastricsin from human gastric juice and human gastric mucosa separated on DEAE-cellulose and isolated by affinity chromatography, were electrophoretically pure. PMID- 3086354 TI - Characterization of pathogenic bacteria by automated headspace concentration-gas chromatography. AB - Automated headspace concentration-gas chromatography (AHC-GC) was used to profile the volatile metabolites produced by Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. Bacterial cultures were incubated in trypticase soy broth and examined at 24 h. The profiles were consistent for each genus examined and variation observed among the different strains of each species was chiefly quantitative. The volatiles were identified by concurrent headspace concentration-gas chromatography-mass spectrometry and consisted mainly of isobutanol, isopentanol, isopentyl acetate, 1-undecene and methyl ketones. There were sufficient differences in the profiles in the 4-6 min elution period to distinguish P. aeruginosa and S. aureus from each other and from the other two bacteria. P. mirabilis and K. pneumoniae typically showed three intense peaks which corresponded to isobutanol, isopentyl acetate and isopentanol. The determination of volatiles by AHC-GC is sensitive, rapid and offers a possible alternative for automatic detection and characterization of pathogenic bacteria. PMID- 3086355 TI - Assessing illness severity: does clinical judgment work? AB - Accurate classification of clinical severity is important for interpreting casemix in clinical studies and for stratifying patients for clinical trials. To evaluate whether clinical judgment might be an effective method of estimating severity, all 604 patients admitted to the medical service in a one month period were rated at the time of admission by the responsible resident as to how sick they were. Within the 13 comorbid disease groups, and within the 15 basic categories of reason for admission, the physicians' severity ratings were the most significant predictor of in-hospital mortality. Death rates rose from 0% in those rated as not ill, to 2% in the mildly ill, to 6% in the moderately ill, to 23% in the severely ill, and to 58% in those rated as moribund (p less than 0.001). Sickness ratings also predicted time to death: mildly ill patients died after prolonged hospitalizations, while the moribund died shortly after admission. The patients' age, sex, race, the number of comorbid diseases or problems did not predict mortality. Patients with serious comorbidity (metastases, AIDS, or cirrhosis) had a higher mortality rate than other patients (p less than 0.001); however, the severity ratings predicted outcomes within this group (p less than 0.001) as well as among those without such serious comorbidity (p less than 0.001). Patients who were admitted with acute neurologic (p less than 0.05) or acute cardiovascular (p less than 0.01) events did have an independently worse prognosis. In conclusion, physicians' estimates or sickness provided an accurate estimate of illness severity, with mortality rates that essentially tripled from one stratum to the next. Clinical judgment may suffice to classify the clinical severity of patients at the time of enrollment in prospective trials and can provide a useful method of controlling for casemix. PMID- 3086356 TI - Growth hormone (GH) responses to GH-releasing hormone during pubertal development in normal boys and girls: comparison to idiopathic short stature and GH deficiency. AB - The normal ranges for GH responses to GH-releasing hormone (GHRH) have previously been defined for adult men and women. To determine whether the GHRH responses of normal children differ from those of adults and whether children with GH deficiency (GHD) and children who are growing below the first percentile but are otherwise normal (ISS) have GH responses comparable to those of normal children, we studied 90 normal children, 46 girls and 44 boys, with heights between the 10th and 95th percentiles for age, at different pubertal stages. Their responses were compared to those of 24 children with ISS and 32 children with GHD and to values previously measured in young adult men and women. Girls were grouped by Tanner breast stages and boys by testicular volumes. Plasma somatomedin-C, estradiol or testosterone, and bone age were measured in all children. All received a 1 microgram/kg iv bolus dose of GHRH-(1-44)NH2, and GH responses were measured during a 2-h sampling period. Incremental serum GH responses in girls did not change throughout pubertal development and were similar to those of adult women. The responses in boys at midpuberty were somewhat lower (P less than 0.05) than those in either prepubertal boys or adult men. ISS children had mean GH responses [23 +/- 4 (+/- SE) ng/ml] similar to those of normal children. GHD children had significantly lower mean GH responses (11 +/- 3.7 ng/ml) than normal prepubertal children (35 +/- 4.0 ng/ml; P less than 0.01), but the responses of 17 of the 32 GHD children overlapped with the normal range. GH responses to GHRH were not correlated with bone age, weight, height, SmC levels, or estradiol or testosterone concentrations. These results indicate that GH responses to GHRH testing are relatively constant throughout puberty and young adulthood, that ISS children respond normally to GHRH, and that the GHRH test is not a reliable discriminator between individual normal and GHD children. PMID- 3086357 TI - Do androgens directly regulate gonadotropin secretion in the polycystic ovary syndrome? AB - This study was designed to investigate whether androgens directly, independent of their aromatization to estrogens, disrupt gonadotropin secretion in hyperandrogenic women with the polycystic ovary syndrome (PCO). Pulsatile gonadotropin release and gonadotroph sensitivity to GnRH were determined on consecutive study days basally and during a primed continuous infusion of testosterone (T; n = 4; 100 micrograms/h; twice the mean production rate of T in PCO) or dihydrotestosterone (DHT; n = 5; 50 micrograms/h). To determine if the gonadotropin secretory changes during T infusion were secondary to spontaneous variation, four patients had two consecutive basal studies, and all patients received DHT on the third study day. T infusion that increased mean plasma T levels from 76 +/- 12 (+/- SE) to 315 +/- 28 ng/dl produced no significant changes in the amount or pattern of LH release or in LH sensitivity to GnRH. Mean plasma FSH levels decreased slightly but significantly during T infusion (basal, 242 +/- 29 vs. T 226 +/- 30 ng/ml LER-907; P less than 0.05 by two-tailed paired t test), but the pulsatile pattern of FSH release and FSH sensitivity to GnRH did not change. DHT infusion increased plasma DHT levels from 17 +/- 3 to 244 +/- 31 ng/dl, but did not alter the mean levels, pulsatile patterns, or sensitivity to GnRH of LH or FSH. These data suggest that androgens do not directly alter gonadotropin release in PCO. Thus, regulation of the hypothalamic-pituitary axis in women with PCO is different from that in men despite chronic exposure to hyperandrogenemia. PMID- 3086358 TI - Carbidopa plus L-dopa pretreatment inhibits the prolactin (PRL) response to thyrotropin-releasing hormone and thus cannot distinguish central from pituitary sites of prolactin stimulation. AB - Contrary to a previous report, pretreatment of normal men with carbidopa plus L dopa (Sinemet 25/250) markedly inhibited the PRL response to TRH, a stimulus that acts directly on the pituitary. Thus, the results of carbidopa/L-dopa testing cannot be used to determine whether agents that stimulate PRL secretion act on the pituitary or at a higher central nervous system level. PMID- 3086359 TI - Naloxone administration does not affect gonadotropin secretion in agonadal men either basally or during testosterone treatment. AB - Naloxone administration has no effect on plasma gonadotropin levels of agonadal men. The present study was designed to evaluate whether testosterone replacement therapy could restore LH responsiveness to naloxone in such men. We measured plasma LH and FSH levels at 15-min intervals during naloxone infusion (8 mg in 1 min followed by 12 mg in 3 h) and for the following 3 h in a group of agonadal men both before and after at least 2 months of three different schedules of testosterone replacement therapy: 1) testosterone undecanoate, 40 mg three times a day by mouth; 2) testosterone enanthate 200 mg im every 2 weeks; and 3) testosterone enanthate 100 mg im once a week. Mean plasma gonadotropin levels as well as LH pulse frequency did not vary during naloxone infusion vs. placebo either basally or during each testosterone regimen. These results suggest that long term testosterone therapy does not affect the altered opioid modulation of gonadotropin secretion which is present in agonadal men. PMID- 3086360 TI - Contraception in hypertensive women using a vaginal ring delivering estradiol and levonorgestrel. AB - Contraception with a vaginal ring (CVR) that delivers estradiol and levonorgestrel was used during a mean of 15.6 menstrual cycles in 12 hypertensive women. Blood pressure (BP) was measured 5 times on each visit during 2 pretreatment control cycles; during the 1st, 2nd, 4th, 6th, and from the 9th to 12th cycles of CVR use; and again after a 1-month recovery period. No significant change in BP occurred during CVR use in any of the subjects. Plasma renin substrate and antithrombin III activity did not vary significantly, which suggests the utility of administering natural estradiol via the vagina, thus avoiding the first pass effect that occurs with oral contraceptives. Significant decreases in plasma sex hormone-binding globulin, cholesterol, high density lipoprotein cholesterol, phospholipids, and triglycerides occurred, indicating an androgenic effect of levonorgestrel. We conclude that the CVR is a method of contraception that does not elevate BP in hypertensive women. PMID- 3086361 TI - Isoelectric focusing variant thyroxine-binding globulin in American blacks: increased heat lability and reduced serum concentration. AB - Three major bands of T4-binding globulin (TBG) at pH 4.3-4.5 are seen after isoelectric focusing (IEF) of serum. Daiger et al. detected a cathodal shift of all IEF bands in some American blacks, and found that the inheritance of this variant TBG (TBG-S) is X-chromosome linked. However, the properties of the TBG-S molecule and its possible association with changes in thyroid function have not been studied. Based on IEF analysis of 114 serum samples from adult American blacks, the gene frequency of TBG-S was 12.0%, and the genotype distribution was consistent with X-chromosomal linkage. TBG-S and the common type TBG (TBG-C) co occurred exclusively in sera from women, whereas sera from men had only TBG-C or TBG-S, confirming the X-linked inheritance of this variant TBG. At 60 C, TBG-S was denatured with a mean t1/2 of 4.7 +/- 0.9 (+/-SD) min compared to 6.8 +/- 1.1 min for TBG-C (P less than 0.001). Heterozygous females with TBG-CS had an intermediate rate of heat denaturation (t1/2, 5.2 +/- 0.7 min). In vitro mixtures of TBG-S and TBG-C also had intermediate t1/2 values, indicating that the heat lability of TBG-S is inherent to the variant TBG molecule. Heat denaturation resulted in loss of T4-binding activity, which was proportional among corresponding IEF bands for each of the two TBG types. Larger amounts of added T4 were required to protect against the heat-induced denaturation of TBG-S. No changes in the affinity of TBG-S for T4 could be demonstrated by analysis of binding kinetics at O C. Thyroid function tests were carried out in 10 black men with TBG-S and 10 age-matched black men with TBG-C. The mean concentration of total T4 (TT4) of 6.8 +/- 1.5 micrograms/dl in the group of TBG-S men was lower (P less than 0.02) than that in the group of TBG-C men (8.5 +/- 1.3 micrograms/dl). The finding of lower levels of TT4 in men with TBG-S was best explained on the basis of a concomitant reduction of serum TBG concentration (1.41 +/- 0.30 vs. 1.72 +/- 0.23 mg/dl; P less than 0.05). This conclusion was confirmed when no significant difference in mean TT4 concentration was found between the group with TBG-S and another with TBG-C matched by serum TBG concentration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3086362 TI - Growth hormone-releasing hormone infusion in patients with active acromegaly. AB - To determine GH-releasing hormone (GHRH)-stimulated GH secretion in patients with active acromegaly, nine patients received a 50-microgram GHRH-(1-44) bolus dose followed by a 2-h infusion with 100 micrograms GHRH/h, after which a second 50 microgram GHRH bolus dose was given. Serum GH, PRL, and immunoreactive GHRH levels were measured from 2 h before to 1 h after the end of the infusion and compared with hormone levels in six normal subjects subjected to the same protocol. In addition, seven of the nine acromegalic patients received 100 micrograms GHRH as an iv bolus dose, followed by a 2-h saline infusion on a different day. After the 100-micrograms GHRH bolus dose, the mean GH level increased from 55.9 +/- 18.0 (+/- SE) to 148.5 +/- 40.0 ng/ml within 15 min. Thereafter, GH levels decreased and were significantly lower at 90 and 120 min compared to the peak level 15 min after GHRH injection. After the 50-micrograms GHRH bolus dose, all acromegalic patients except two also had a clear-cut rise of GH levels, with the mean GH level increasing from 37.5 +/- 13.2 to 108.4 +/- 55.0 ng/ml at 60 min. Thereafter, elevated GH levels were sustained in the acromegalic patients throughout the GHRH infusion. In contrast, normal subjects had a significant decrease in the initially elevated GH levels, despite continuous GHRH infusion. There were no significant differences between PRL secretion and immunoreactive GHRH levels in either group. These findings suggest that patients with active acromegaly not only have elevated basal GH levels, but also have a greater ready releasable GH pool and/or accelerated GH turnover compared to those of normal subjects, which cannot be exhausted by a 2-h GHRH infusion. PMID- 3086363 TI - An analysis of the cellular requirements for the production of soluble interleukin-2 receptors in vitro. AB - Following activation in vitro, peripheral blood mononuclear cells (PBMC) express cell-associated interleukin-2 receptors (IL-2R) and also release soluble IL-2R into culture supernatants. The present studies were undertaken to define which normal cells were responsible for the release of soluble IL-2R in vitro. Both cell-associated and soluble IL-2R were quantitatively measured with a "sandwich" enzyme-linked immunoassay employing two monoclonal antibodies. PBMC were separated into populations of surface immunoglobulin-negative cells (T cells and monocytes) and surface immunoglobulin-positive cells (B cells and monocytes), and the T-cell population was further separated into OKT4-positive (OKT4+) cells and OKT4-negative (OKT4-) cells. Following activation with phytohemagglutinin, pokeweed mitogen, and the monoclonal antibody OKT3, large amounts of soluble IL 2R were released by PBMC, unseparated T cells, OKT4+ T cells, and OKT4- T cells. The population containing B cells and monocytes made small but readily detectable amounts of soluble IL-2R when stimulated with these T-cell mitogens; likely the result of contaminating T cells in the population. However, when highly purified B cells were stimulated with Staphylococcus aureus Cowan and recombinant IL-2, they also released small amounts of soluble IL-2R. The release of soluble IL-2R by T cells appeared monocyte dependent when OKT3, but not phytohemagglutinin, was employed for activation, and monocytes themselves released no detectable IL-2R under the conditions employed. These studies define the cellular requirements for the release of soluble IL-2R in vitro and demonstrate that such receptors are released by B cells, T cells, and both OKT4+ and OKT4- T-cell subsets. PMID- 3086366 TI - [Effect of thyrotropin-releasing hormone (TRH) on gastric motility in man]. PMID- 3086367 TI - [Growth hormone (GH) response to GH-releasing factor in adult female rats treated with monosodium glutamate during the neonatal period]. PMID- 3086365 TI - Defective gamma-interferon production in peripheral blood leukocytes of patients with acute tuberculosis. AB - Production of interferon (IFN)-gamma by peripheral blood leukocytes (PBL) was examined in cultures of unseparated fresh whole blood exposed to phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM). The yield of IFN-gamma was measured by a newly developed immunoradiometric assay. Nine of 14 patients with acute pulmonary tuberculosis (TB) showed a depressed IFN gamma response to Con A and/or PWM. Only four of these TB patients also showed a depressed IFN-gamma response to PHA. Stimulation of the patients' PBL cultures with PHA in the presence of exogenous interleukin 2 (IL 2) produced normal IFN gamma yields in all but the most severely depressed patients. PBL cultures of TB patients with defective IFN-gamma production in response to mitogenic lectins also produced less IFN-gamma after stimulation with tuberculin PPD. Although some patients showed a moderate degree of lymphopenia, their OKT4/T8 lymphocyte ratios were mostly normal or close to normal, with the notable exception of one TB patient who has been diagnosed to have the acquired immune deficiency syndrome (AIDS). PMID- 3086364 TI - Progressive change in lymphocyte distribution and degree of hypergammaglobulinemia with age in children with hemophilia. AB - Fifty asymptomatic, pediatric hemophiliacs were examined for distribution of T cell subsets, responsiveness to mitogen stimulation, interleukin-2 production, hypergammaglobulinemia, and the presence of antibody to virus including the human T-lymphotrophic virus type III (HTLV-III). Hemophilia A patients receiving factor VIII concentrate as replacement therapy had the most pronounced changes including decreased T4/T8 ratios and lower in vitro responsiveness to both phytohemagglutinin and pokeweed mitogen. Hemophilia A patients treated with cryoprecipitate and hemophilia B patients did not demonstrate these changes. Regardless of replacement therapy, hemophiliacs demonstrated a progressive decrease in the T4/T8 ratio and a progressive increase in the degree of IgG hypergammaglobulinemia as they aged. The amount of factor or cryoprecipitate or exposure to virus did not influence the T4/T8 ratio. These changes appear to be a result of chronic product exposure, which becomes more pronounced with increasing age. PMID- 3086368 TI - Immunodiffusion test for diagnosing and monitoring pythiosis in horses. AB - A practical, sensitive, and specific immunodiffusion test was developed for diagnosing and monitoring pythiosis in horses. Culture filtrates, a soluble cell mass, and trypsinized Pythium sp. antigens were evaluated against prepared rabbit anti-Pythium sp. serum and pythiosis horse case sera. The culture filtrate antigens demonstrated the greatest capacity for detecting precipitins and the greatest stability during storage. In contrast, the trypsinized antigens had the weakest capability for detecting multiple precipitins and the poorest stability. The 13 sera from horses with proven active pythiosis were positive in immunodiffusion tests with the culture filtrate antigens. Each serum contained from three to six precipitins. Treated horses lost precipitins, and some became antibody negative. No false-positive reactions were noted in tests with sera from normal horses and humans or with sera from a variety of heterologous horse and human infections. PMID- 3086369 TI - Determination of mycobacterial antigens in sputum by enzyme immunoassay. AB - An enzyme-linked immunosorbent assay (ELISA) was examined for its usefulness in detecting mycobacterial antigens in sputum. A double-antibody sandwich procedure was set up by using a commercially available hyperimmune serum directed against Mycobacterium bovis, BCG. The ELISA was able to detect 10 ng of protein per ml of BCG sonic extract. The system also clearly distinguished Mycobacterium tuberculosis organisms from Mycobacterium avium and Mycobacterium kansasii organisms. A total of 68 unknown sputum specimens submitted to the clinical laboratories for examination for tuberculosis were tested by ELISA. Of the 20 specimens that were smear positive and culture positive, 12 (60%) were positive by ELISA; 6 of the 11 (55%) smear-positive culture-negative samples were positive by ELISA; 1 of 2 (50%) of the smear-negative culture-positive samples was positive by ELISA; and only 3 of 35 (9%) of the smear-negative culture-negative samples were positive by ELISA. This approach offers promise as an aid in the presumptive differentiation of nontuberculous mycobacteria from the M. tuberculosis complex. PMID- 3086370 TI - Sensitivity and specificity of enzyme-linked immunosorbent assay in the detection of antigen in tuberculous meningitis cerebrospinal fluids. AB - A sandwich enzyme-linked immunosorbent assay was developed for its potential utility in the detection of antigen in the cerebrospinal fluid of patients with tuberculous meningitis. Cerebrospinal fluids examined included those from untreated (group Ia) and treated (group Ib) Mycobacterium tuberculosis meningitis, nonseptic central nervous conditions (group II) such as epilepsy, viral meningitis, and tetany, and nonmycobacterial septic meningitis (group III). The average levels of antigens determined and percent positive specimens, respectively, for each group were (group): Ia, 1.8 micrograms/ml and 75% positive; Ib, 0.37 microgram/ml and 36% positive; II, 0.036 microgram/ml and 100% negative; and III, 0.075 microgram/ml and 100% negative. The system developed employed hyperimmune polyclonal antibody raised against M. tuberculosis and Mycobacterium bovis BCG in burros and rabbits. Cross-reactivity by other mycobacterial species was very low; e.g., 5% for M. kansasii and less than 2% for M. intracellulare, M. avium, M. vaccae, and M. fortuitum. The test shows promise as a specific adjunct for the early diagnosis of tuberculous meningitis. PMID- 3086371 TI - Nonweekend schedule for BACTEC drug susceptibility testing of Mycobacterium tuberculosis. AB - Determination of the drug susceptibility of Mycobacterium tuberculosis by conventional methods using an agar-based medium may take 3 weeks or more to complete. On the other hand, results on positive cultures are generally available in 4 to 7 days with the radiometric (BACTEC, Johnston Laboratories, Towson, Md.) procedure. One disadvantage to the latter is the requirement to determine the quantity of 14CO2 in each test vial on a daily basis from the day of inoculation. Growth index readings often must be made over weekends, adding to the work load of clinical laboratories during periods of reduced staff or necessitating compensatory pay or time. Susceptibility tests with streptomycin, isoniazid, ethambutol, and rifampin against 104 M. tuberculosis strains were performed by the submerged disk method, the recommended BACTEC method with daily growth index readings, and the radiometric procedure with readings delayed for 2 days after inoculation. Criteria for interpretation of "delayed" tests were established. Drug concentrations tested included some modifications of those available commercially. Overall agreement for the four drugs by the three methods was greater than 90%. We conclude that under our test conditions a schedule of inoculation of radiometric test vials on Friday with growth index readings commencing on Monday gives susceptibility results that correlate well with the daily BACTEC method and with a conventional 7H10 agar method. PMID- 3086372 TI - Production of elastase and other exoproducts by environmental isolates of Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa isolates from environmental sources and bacteremic patients were compared for their levels of elastolytic activity. No significant differences were found. The incidence of production of toxin A, phospholipase C, alkaline protease, and elastase among the environmental strains was also as high as that previously reported for clinical isolates. PMID- 3086373 TI - Characterization of Neisseria polysacchareae sp. nov. (Riou, 1983) in previously identified noncapsular strains of Neisseria meningitidis. AB - A study of 216 noncapsular strains of Neisseria meningitidis isolated from patients and carriers received in the Meningococcus Reference Laboratory between 1978 and 1984 is reported. The characterization of the strains consisted of biochemical tests for the following characteristics used for the differentiation of Neisseria species: oxidase, catalase, and beta-galactosidase activities; sugar degradation; nitrate and nitrite reduction; DNase activity; polysaccharide production with 5% sucrose; aminopeptidase activity; and growth in Thayer-Martin and Catlin media. Of the strains studied, 50 showed characteristics of a new taxon recently described (Neisseria polysacchareae). Characteristics that differentiated these strains from meningococcal isolates were polysaccharide production with 5% sucrose, gamma-glutamylaminopeptidase activity, and a requirement for cysteine or cystine for growth in Catlin medium. All of the N. polysacchareae strains identified were isolated from the nasopharynx of healthy carriers. PMID- 3086374 TI - Some antigenic properties of Haemophilus parasuis and a proposal for serological classification. AB - We propose a serological classification of Haemophilus parasuis into at least five serovars, using an agar-gel-precipitation test with extracts from autoclaved cells. Thirty-two strains were examined, and it was possible to classify 26 of them. The specific antigens were thermostable and soluble and were not affected by pronase treatment but could be extracted by phenol, suggesting a polysaccharide. This polysaccharide seemed to be identical with the capsular substance of serovars 1, 2, and 3. In the presumably uncapsulated strains of serovars 4 and 5, the specific antigen was probably located in the outer membrane. The diversity of the specific substance within the different serotypes was shown by the differences in their electrophoretic migration patterns. Other extraction procedures showed that the washing supernatant and extracts at 60 and 100 degrees C were identical with the 121 degrees C extracts for serovars 1, 2, and 3. In serovars 4 and 5, washing antigens, if present, were different from 100 and 121 degrees C extracts. Other common antigens, presumably proteinaceous antigens, were detected after extraction at 60 and 100 degrees C. The slide and tube agglutination tests allowed classification only for the capsulated strains of serovars 1, 2, and 3. The specific agglutinogens were very sensitive to incubation temperature, and the absorption test showed them to be identical with the 121 degrees C precipitinogens. PMID- 3086376 TI - In vitro study of bacterial growth in continuous ambulatory peritoneal dialysis fluids. AB - We examined the in vitro survival of bacteria in continuous ambulatory peritoneal dialysis effluents of patients with clinical peritonitis and those without peritonitis. Standard strains of coagulase-negative staphylococci (CNS), Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were inoculated into the fluids, and portions were plated for bacterial counts at 0.5, 4, 24, 48, 72, and 96 h. Unused dialysate fluid was also inoculated simultaneously. Our results show that CNS increased minimally up to 48 h in the noninfected continuous ambulatory peritoneal dialysis effluents and decreased by 96 h, whereas survival was only minimal in the infected effluent. S. aureus showed trends similar to those of CNS, but differences in survival in infected and noninfected effluents were less marked. By contrast, E. coli and P. aeruginosa increased by greater than 1,000-fold in all solutions tested. Based on the above findings, it is likely that a proportionate number of culture-negative cases of peritonitis are due to gram-positive cocci, especially CNS, which are not retrievable by standard culture techniques because of poor survival rate. PMID- 3086375 TI - Direct identification and susceptibility testing by the AutoMicrobic system of gram-negative bacilli from urine specimens. AB - A total of 1,800 urine specimens were screened by Gram stain to detect bacteriuria. Pellets of bacteria were obtained by centrifuging specimens containing greater than or equal to 1 gram-negative bacillus of a single morphological type per oil immersion field. Direct susceptibility tests and identifications were performed from pellets by using the AutoMicrobic system (AMS). Results were compared with culture results by routine AMS methods. Of the 145 specimens showing only gram-negative bacilli on Gram stain, 113 grew greater than or equal to 10(5) CFU of a single species per ml. Compared with routine AMS identifications, the direct method correctly identified 105 (92.9%) of the isolates. Identifications were available within 8 h for 77% of the isolates. When compared by MICs, 93.2% of the direct susceptibility test results agreed with routine AMS results within one twofold dilution. Comparisons by category call indicated that overall complete and essential agreements were 89.9 and 97.8%, respectively, with 1.0% very major, 1.0% major, and 8.1% minor errors. Cefamandole and cephalothin had the lowest correlations by both comparisons. Within 8 h, susceptibility results were available for 94.3% of the isolates. This method offers the advantage of rapid detection, prompt processing, and earlier reporting of complete results for positive urine specimens. PMID- 3086377 TI - Imipenem susceptibility testing with a commercially prepared dry-format microdilution tray. AB - MICs of imipenem, concurrently generated in commercially prepared microdilution trays containing predried antibiotic dilutions (Sensititre), and in a standard agar dilution assay (as recommended by the National Committee for Clinical Laboratory Standards, Villanova, Pa.), were within +/- 1 twofold dilution for 94% of 226 bacterial isolates. Imipenem biological activity remained stable over 5 months of tray storage at room temperature against Pseudomonas aeruginosa ATCC 27853. Activity of imipenem was shown by microdilution testing with 890 clinical isolates to be high, with only 4% of isolates having MICs of greater than or equal to 16 micrograms/ml (in vitro resistance). PMID- 3086379 TI - Characterization of increased Ca2+ efflux by quercetin from the sarcoplasmic reticulum in frog skinned skeletal muscle fibres. AB - To clarify further the characteristics of the Ca-releasing action of quercetin, we examined the effect of quercetin on Ca2+ efflux from the sarcoplasmic reticulum without Ca uptake activity by omission of ATP in the presence of a high concentration (10 mM EGTA) of Ca2+ buffer, using mechanically skinned fibres from frog skeletal muscles. Quercetin increases the rate of Ca release in the presence of Ca2+ and shifts the relationship between Ca2+ concentration and the rate of Ca release to a lower range of Ca2+ concentrations. AMP potentiates the effect of quercetin. Mg2+ and procaine decrease the rate of Ca release in the presence of quercetin. These findings indicate that quercetin is very similar to caffeine; in fact, experiments confirmed that quercetin shares the site(s) of action with caffeine. Subsequent findings, however, suggest that the mechanism of the drug induced Ca release is not as simple as expected with caffeine which may increase the affinity for Ca2+ of the 'Ca2+-induced Ca-release' mechanism, and that drugs, Ca2+ and nucleotide interact with one another in a more complex way to open the gate for Ca release. In the presence of 10 mM EGTA quercetin also causes Ca release in the virtual absence of Ca2+ if a sufficient amount of AMP is present, and the rate of Ca release in the presence of 1.55 micron Ca2+ showed different dependence on AMP concentration with and without quercetin. A higher concentration of Mg2+ is required in the presence of AMP than in the absence of AMP in order to eliminate Ca release by quercetin. PMID- 3086380 TI - A double-label flow cytometric analysis of the simultaneous expression of OKT4 and Leu2a antigens on circulating T lymphocytes in myasthenia gravis. AB - A two-color immunofluorescence analysis of circulating abnormal T lymphocytes bearing both helper (T4) and suppressor/cytotoxic (Leu2a) T cell markers (double marker cells) was performed by means of the laser flow cytometry system. The double marker cell level was very low in 6 patients with multiple sclerosis and 12 normal controls studied. Fifteen of 31 patients with myasthenia gravis (MG) showed an elevation of double marker cells without an increase in T6-positive cells. The values were significantly higher in patients with thymoma or thymic hyperplasia than in those with a normal thymus. The double marker cell level was considered to reflect thymic abnormality in MG and to be helpful for determining the indication of thymectomy. PMID- 3086378 TI - The effects of a 45 000 molecular weight protein from unfertilized sea urchin eggs and its 1:1 actin complex on actin filaments. AB - A 45 kDa actin-binding protein (SU45) has been isolated previously from egg extracts of the Hawaiian sea urchin Tripneustes gratilla by DEAE Sephacel, Sephadex G-75 and hydroxyapatite chromatography. Using pyrene-labelled rabbit skeletal muscle actin, we have found that when SU45 is added to actin in the presence of calcium and the salt concentration is increased, the initial rate of actin assembly is accelerated. Moreover, the final polymer concentration is reduced indicating that SU45 caps the preferred end of actin filaments shifting the critical concentration (Cc) to that of the nonpreferred end. Determination of the Cc as a function of the concentration of SU45 gave an apparent KD of 1 nM. Dilution of F-actin to below its Cc, into buffers containing SU45 and Ca2+ resulted in a sharp increase in the rate of depolymerization; reducing the Ca2+ concentration attenuated this effect. Incubation of SU45 with rabbit skeletal muscle G-actin yielded a 1:1 complex which held 45Ca2+ tightly with a dissociation half-time of 10.8 days. By kinetic analyses of assembly in the presence of the SU45-actin complex and dilution-induced disassembly of filaments precapped with complex, we have estimated both the association rate constant (4.0 X 10(4)M-1s-1) and the dissociation rate constant (0.05s-1) for the nonpreferred ends of actin filaments. Finally, dilution of F-actin to below its Cc, into complex in either Ca2+ or EGTA resulted in a much slower depolymerization consistent with a rapid capping of the preferred end by the SU45-actin complex. PMID- 3086381 TI - Astrocytes as antigen-presenting cells. Part II: Unlike H-2K-dependent cytotoxic T cells, H-2Ia-restricted T cells are only stimulated in the presence of interferon-gamma. AB - Various studies strongly suggest that astrocytes are potent immune-regulating cells. They can be activated to release prostaglandin E, interleukin-1- and interleukin-3-like factors. Cocultivation of antigen-specific T cell lines and astrocytes results in induction of Ia on astrocytes and antigen-specific proliferation of T cells. In the current study, astrocytes were found to be incapable of serving as stimulator cells when unprimed T lymphocytes were used as responders in syngeneic or allogeneic lymphocyte reactions. However, when interferon-gamma (IFN-gamma) was added, astrocytes became Ia positive and potent stimulators in both syngeneic or allogeneic lymphocyte responses. In the presence of IFN-gamma, astrocytes presented antigens to Ia-restricted T hybridoma cells; in contrast hapten was presented to Kb-restricted cytotoxic cloned T cells by astrocytes in the absence of IFN-gamma. Thus, cultured astrocytes do function directly as accessory cells in class I antigen-dependent T cell activation, whereas Ia induction by IFN-gamma is necessary to enable them to present antigen to class II antigen-restricted T cells. PMID- 3086382 TI - Pituitary self-priming actions of gonadotropin-releasing hormone. Kinetics of estradiol's potentiating effects on gonadotropin-releasing hormone-facilitated luteinizing hormone and follicle-stimulating hormone release in healthy postmenopausal women. AB - We examined the kinetically distinct characteristics of estradiol's effects upon pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in response to pulses of exogenous gonadotropin-releasing hormone (GnRH) in healthy postmenopausal individuals. The putative self-priming actions of GnRH on LH and FSH release were tested by intravenous injections of equal paired doses of GnRH (10 micrograms) before and after 1, 5, 10, and 30 d of pure estradiol-17 beta delivery via an intravaginal silastic ring. Self-priming actions of GnRH, as defined by heightened gonadotropin release in response to the second pulse of GnRH compared with the first, were completely absent in the hypoestrogenemic state. However, estradiol administration unmasked GnRH self-priming in a time dependent fashion, with maximal expression after 5 and 10 d of steroid replacement, followed by attenuation by 30 d. Since estradiol's modulation of GnRH action was expressed differentially on LH and FSH release, we suggest that such facilitation of GnRH-stimulated pituitary LH and FSH release may provide an additional mechanism for dissociated secretion of gonadotropic hormones in health or disease. PMID- 3086383 TI - Studies of human megakaryocytopoiesis using an anti-megakaryocyte colony stimulating factor antiserum. AB - We produced an antiserum by immunizing rabbits with purified human megakaryocyte colony stimulating factor (Meg-CSF). With the use of an anti-Meg-CSF IgG fraction (AM-IgG), we detected immunoreactive Meg-CSF both in human aplastic anemia serum (AAS) and normal serum. Based on our immunological and biological analyses, Meg CSF appeared to be antigenically as well as functionally distinct from human urinary erythropoietin (EPO) and thrombopoietic stimulating factor. The AM-IgG fraction was able to suppress the ability of both aplastic anemia serum and purified Meg-CSF to promote megakaryocyte colony formation. In addition, the supernatant formed after immune precipitation of the AAS with AM-IgG no longer possessed Meg-CSF-like activity. The AM-IgG did not suppress the ability of EPO, phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM), or PHA-LCM + EPO to promote erythroid, granulocyte-macrophage, or mixed colony formation, respectively. The use of this antibody has further defined the dependency of human megakaryocytopoiesis on Meg-CSF. PMID- 3086384 TI - Effects of DNA and prostaglandin synthesis inhibitors on the stimulation of bone resorption by epidermal growth factor in fetal rat long-bone cultures. AB - We examined two inhibitors of DNA synthesis, hydroxyurea (HU) and aphidicholin (APC), and two inhibitors of prostaglandin cyclooxygenase, indomethacin and flufenamic acid, for their effects on the resorptive responses of fetal rat long bone cultures to epidermal growth factor (EGF) and parathyroid hormone (PTH). As we have previously found, HU decreased unstimulated 45Ca release but had little effect on the resorptive response to PTH. HU also did not block resorption stimulated by EGF. Addition of the cyclooxygenase inhibitor, indomethacin, did not alter the resorptive responses of unstimulated or PTH-treated cultures in either the presence or absence of HU or the resorptive response of bones cultured with EGF alone. However, indomethacin completely blocked the resorptive response to EGF of bones that were cultured with HU. The effects of indomethacin on EGF mediated resorption in HU-treated cultures appeared to be related to an inhibition of prostaglandin synthesis since flufenamic acid had similar effects. However, the effects of HU on the resorptive response to EGF may not have resulted solely from its inhibitory action on DNA synthesis since APC, in the absence of cyclooxygenase inhibitors, completely blocked EGF-mediated resorption without significantly affecting the response to PTH. These results demonstrate that the mechanisms regulating PTH- and EGF-mediated resorption in fetal rat long bone cultures differ, and imply that a component of EGF-mediated resorption in these cultures is dependent on sustained DNA synthesis. PMID- 3086386 TI - A note on the recovery of micro-organisms from an oil-in-water cream. AB - The isolation of micro-organisms from the oil-in-water Aqueous Cream BP, has been examined using a variety of solvent systems to disperse the cream prior to membrane filtration or direct inoculation. Pour-plate methods which utilize combinations of either peptone-water (containing 5% w/v polysorbate 80) or nutrient broth (containing 4% w/v Lubrol W) provided the most efficient recovery of Pseudomonas aeruginosa but still allowed less than 20% recovery. White spirit and isopropyl myristate allowed no recovery when used as dispersants. Recoveries of P. aeruginosa varied according to the source of the cream. A combination of 1% w/v polysorbate 80 in 0.1% w/v peptone-water and membrane filtration allowed 63.2% w/v and 67.0% w/v recoveries respectively of Aspergillus niger and Candida albicans from unpreserved aqueous cream, but gave unreproducible results for Escherichia coli and P. aeruginosa. Chlorocresol 0.1% w/v) did not meet the British Pharmacopoeial requirements for efficacy of antimicrobial preservatives when tested against C. albicans using membrane filtration to isolate the micro organism. PMID- 3086387 TI - An investigation of the in vitro anti-bacterial activity of noxythiolin against 1,000 pathogenic bacterial isolates. AB - The susceptibility of 1,000 recent bacterial isolates to noxythiolin was determined by the disc susceptibility method. No Gram-positive strains were resistant to this method but 56 (5.6%) of Gram-negative strains gave zones of inhibition of 12 mm diameter or less. The minimum inhibitory concentration (MIC) of the latter were determined by the agar incorporation method. No strains had MIC values greater than 4096 mg/litre. Since concentrations of 50,000 mg/litre can be used for topical treatment, these organisms may be considered susceptible. PMID- 3086385 TI - Plasminogen interacts with human platelets through two distinct mechanisms. AB - Glu-plasminogen, the native form of plasminogen, interacts in a specific and saturable manner with unstimulated human platelets, and the binding is enhanced fivefold by thrombin stimulation (Miles and Plow, 1985. J. Biol. Chem. 260:4303). This study characterizes the nature of the Glu-plasminogen binding sites by analyzing platelets deficient in selected proteins and functions. Platelets from patients with afibrinogenemia, Gray platelet syndrome, and the Cam Variant of thrombasthenia, a form of thrombasthenia with near normal levels of glycoprotein IIb/IIIa (GPIIb/IIIa), showed minimal augmentation of plasminogen binding to thrombin-stimulated platelets but normal binding to unstimulated platelets. This selective deficiency indicates that two distinct mechanisms are involved in the interaction of plasminogen with platelets. These abnormal platelets share a deficiency in fibrinogen. Surface expression of platelet fibrinogen, however, was not sufficient for enhanced plasminogen binding to stimulated platelets, and experiments with alpha-thrombin and gamma-thrombin indicated that fibrin formation on the platelet surface is necessary for the augmented plasminogen binding. Unstimulated and stimulated thrombasthenic platelets deficient in GPIIb/IIIa bound markedly reduced levels of plasminogen, which suggests a role for GPIIb/IIIa in plasminogen binding to unstimulated platelets. Treatment of platelets to dissociate the heterodimeric complex of GPIIb/IIIa did not significantly perturb plasminogen binding to unstimulated platelets, but the complex may be necessary for thrombin-stimulated plasminogen binding via its interaction with platelet fibrin. PMID- 3086389 TI - Epidermolysis bullosa acquisita: clinical response to plasma exchange therapy and circulating anti-basement membrane zone antibody titer. AB - Epidermolysis bullosa acquisita has been recognized as a rare autoimmune mechanobullous disorder since the detection of immunoglobulin and complement deposits along the basement membrane zone. A circulating anti-basement membrane zone antibody has also been detected in some cases. We are reporting a case of epidermolysis bullosa acquisita in which clinical symptoms were well correlated with the circulating anti-basement membrane zone antibody titers. Although the patient initially responded very well to corticosteroid therapy, remission could not be maintained without increasing the dosage. Other therapies, including azathioprine, dapsone, vitamin E, and gold sodium thiomalate, produced no beneficial effects. Although a high dose of oral corticosteroid and cyclophosphamide decreased the antibody titer and blister formation, this therapy had to be terminated because of side effects. Plasma exchange therapy in combination with corticosteroid and low-dose cyclophosphamide resulted in a marked decrease of the anti-basement membrane zone antibody titer and clinical improvement. Thus plasma exchange therapy may be a useful adjunct to conventional treatments for patients with epidermolysis bullosa acquisita. PMID- 3086391 TI - Linear porokeratosis: treatment with the carbon dioxide laser. AB - A patient with a lifelong linear porokeratosis was treated with a carbon dioxide laser. The laser was successful in removing the patient's hyperkeratotic plantar lesion. No recurrence has been noted in a 6-month follow-up visit. This report demonstrates another dermatologic condition that can be treated successfully with the CO2 laser. PMID- 3086388 TI - Use of rifampin with penicillin and erythromycin in the treatment of psoriasis. Preliminary report. AB - The addition of 5 days of rifampin therapy to a 10- or 14-day course of penicillin or erythromycin therapy has been shown to reduce greatly the rate of chronic streptococcal carriage. The empiric use of rifampin in combination with penicillin or erythromycin in nine of nine patients with streptococcal-associated psoriasis appeared to coincide with a marked improvement in their skin. PMID- 3086390 TI - Scleromyxedema associated with scleroderma renal disease and acute psychosis. AB - Scleromyxedema is a rare cutaneous disease with occasional systemic involvement and characteristic poor response to treatment. A case of scleromyxedema associated with renal scleroderma and acute psychosis is presented, along with a review of treatment and associated internal disorders. PMID- 3086392 TI - A practitioner-based adult oral health monitoring system. PMID- 3086393 TI - The future of dentistry in the next twenty years. PMID- 3086394 TI - Chronology of dentistry: a Connecticut perspective. PMID- 3086395 TI - "Vignettes" or a portrayal of Horace Wells. PMID- 3086396 TI - A proud dental heritage. Horace H. Hayden and the Connecticut connection. PMID- 3086397 TI - The Historical Museum of Medicine and Dentistry of the Hartford Medical Society and Hartford Dental Society. PMID- 3086398 TI - Self-directed learning for staff development. PMID- 3086399 TI - Notes on continuing education: Self-Directed Learning Network. PMID- 3086401 TI - Getting the most from course faculty. Administrative angles. PMID- 3086400 TI - Self-directed learning. Teaching tips. PMID- 3086402 TI - Recent developments in self-directed learning. PMID- 3086403 TI - Self-directed learning in voluntary and mandatory continuing education programs. PMID- 3086404 TI - Self-directed learning about computers and computers for self-directed learning. PMID- 3086405 TI - Factors to consider in the development of self-instructional materials. PMID- 3086406 TI - Self-directed learning in a critical care nursing program. PMID- 3086407 TI - Determination of the extracellular and cell-associated hydrolase profiles of Pseudomonas fluorescens sp. using the Analytab API ZYM system. AB - The extracellular and cell-associated hydrolase profiles of a number of Pseudomonas fluorescens strains were examined with the Analytab API ZYM system. Esterase/lipase was the only strong extracellular enzyme activity detected (mean 3.33): weak esterase, lipase, and leucine aminopeptidase activities were found with some strains (mean activities of 1.08, 1.53, and 1.40, respectively). Very strong leucine aminopeptidase activity (4.5) was associated with the cells. Cell associated trypsin, esterase/lipase, acid phosphatase, and phosphoamidase were also found. Neither extracellular nor cell-associated hydrolase profiles changed significantly when cells were grown in skim milk or mineral salts medium at either 5 or 20 degrees C. Similarly, added calcium did not seem required for synthesis of any of the enzymes. The extracellular enzyme profiles differed considerably from those of the cell-associated enzymes for all strains tested. An extracellular proteinase-deficient mutant of strain 32A (RM14) failed to produce significant quantities of extracellular esterase/lipase activity. Production of cell-associated enzymes was unaffected by the mutation. These results suggest that the Analytab API ZYM system may be useful in identifying psychrotrophs isolated from milk. PMID- 3086408 TI - Efficacy of fluoride on dental caries reduction by means of a community water supply. AB - A study of 200 children, patients of the City of New Orleans Health Department Bureau, was made to determine the effects of a fluoridated water supply (the Mississippi River) on their caries experience. Results show that drinking water is a very cost-effective vehicle of fluoride administration, and that a fluoridated community water supply does indeed reduce the numbers of caries lesions and extractions. PMID- 3086409 TI - Production and degradation of formate by Veillonella dispar ATCC 17745. AB - Under strictly anaerobic conditions, the resting cells of V. dispar ATCC 17745 produced formate as well as acetate and propionate from pyruvate or from lactate. Pyruvate formate-lyase activity was found when the activity was assayed under strictly anaerobic conditions. Under aerobic conditions, however, the resting cells did not produce formate from pyruvate or from lactate, though the cells actively metabolized pyruvate or lactate (mainly to acetate). This was ascribed to pyruvate formate-lyase activity being easily lost when the cell-free extract was exposed to the air. A part of the produced formate was further degraded to CO2 by the resting cells. PMID- 3086411 TI - Carbon dioxide laser treatment of epidermal nevi. AB - Techniques and results of CO2 laser vaporization of epidermal nevi in 15 patients over a 5-year period is presented. This procedure provides an alternative and effective surgical method for the successful removal of such lesions. PMID- 3086410 TI - Hamster cheek pouch carcinoma: effect of incision and cortisone on growth, invasion, and metastasis. AB - After cheek pouch carcinomas were induced in hamsters by the application of dimethylbenzanthracene (DMBA) to the right pouch for 13 weeks, the animals were divided into four groups and observed for seven more weeks. The control group received no further treatment, two experimental groups had incisional biopsies performed on tumors in their pouches, one of these also received injections of cortisone throughout the 20-week experimental period, and a fourth group received cortisone only. The wet weights of the cancerous cheek pouches were determined, and the submandibular and parotid salivary glands with associated cervical lymph nodes, the lungs, and the liver were examined with light microscopy. The cancerous pouches of the animals that received cortisone weighed significantly less than those of animals that received no cortisone but had incisional biopsies of the tumors. There was no significant difference in the degree of histodifferentiation of the tumors among the four groups. The animals in the two groups that received cortisone had significantly more tumors that were invasive than did the animals that did not receive cortisone. Cervical lymph node metastasis occurred in 21% to 38% of the animals but was not significantly different in the four groups. Distant metastases to the lungs or the liver were not found. Incisional biopsy of the tumors stimulated local growth of the cheek pouch tumors, and systemic cortisone administration produced more invasive cheek pouch tumors. PMID- 3086412 TI - Diverticular disease. PMID- 3086413 TI - Suppression of spontaneous breathing during high-frequency jet ventilation. Influence of dynamic changes and static levels of lung stretch. AB - Conditions which suppress spontaneous breathing activity during high-frequency jet ventilation (HFJV) were analysed in Yorkshire piglets under pentobarbital anesthesia. The highest PaCO2 at which the animals did not breathe against the ventilator (apnea point) was established during different patterns of ventilation, either by changing the minute volume or by adding CO2 to the inspiratory gas. Arterial oxygen tension was maintained throughout the study above 80 mm Hg. An elevation of ventilatory rate increased the apnea point, suggesting a progressive suppression of spontaneous breathing. This suppression did not depend on the amount of lung stretch during insufflation, because at higher rates lower tidal volumes were used. Suppression also appeared to be independent of insufflatory flow, i.e. the velocity of lung stretch. At higher frequencies end-expiratory airway pressure (PEE) increased and there appeared to be a positive relationship between the apnea point and PEE. In a separate series this positive relationship between the apnea point and PEE was confirmed. A hysteresis effect in this relationship, however, suggests that other than jet frequency, lung volume rather than positive end-expiratory pressure (PEEP) is a major determinant of suppression of spontaneous breathing activity during HFJV. PMID- 3086415 TI - Illness in a veterinary student following accidental inoculation of Brucella abortus strain 19. PMID- 3086416 TI - Coronary thrombolysis by intravenous infusion of recombinant single chain urokinase-type plasminogen activator or recombinant urokinase in baboons: effect on regional blood flow, infarct size and hemostasis. AB - An occlusive thrombus was produced by thrombin-induced coagulation in the left anterior descending coronary artery of 18 open chest baboons. In six control animals, occlusive thrombosis persisting for 4 hours resulted in a large transmural infarct (66 +/- 4% of the perfusion area, mean +/- SEM). In six animals, single chain urokinase-type plasminogen activator, obtained by recombinant deoxyribonucleic acid (DNA) technology, was infused intravenously at a rate of 20 micrograms/kg per min for 60 minutes after approximately 45 minutes of coronary thrombosis. Persistent reperfusion occurred within 21 +/- 4 minutes (mean +/- SD). The mean duration of occlusion before reperfusion was 72 +/- 6 minutes. Recanalization resulted in a reduction of infarct size (42 +/- 4%, p less than 0.01 versus control animals). Myocardial blood flow in the perfusion area of the left anterior descending coronary artery was 107% of normal 2.5 hours after recanalization. The infusion of recombinant single chain urokinase-type plasminogen activator was not associated with systemic activation of the fibrinolytic system, fibrinogen breakdown or evident bleeding. In six baboons recombinant low molecular weight urokinase (molecular weight 33,000) was infused intravenously at a rate of 20 micrograms/kg per min for 60 minutes after approximately 45 minutes of coronary thrombosis. Persistent reperfusion occurred within 14 +/- 5 minutes (p less than 0.05 versus recombinant single chain urokinase-type plasminogen activator). The mean duration of occlusion was 69 +/- 14 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086414 TI - Acute renal failure in diabetics. PMID- 3086417 TI - Beneficial effects of tissue-type plasminogen activator in acute myocardial ischemia in cats. AB - Tissue-type plasminogen activator is a new thrombolytic agent that dissolves intravascular thrombi in coronary and peripheral vessels with less pronounced systemic lysis than that produced by streptokinase. Plasminogen activator was shown to induce reperfusion, and to salvage ischemic myocardium, by lysing experimentally induced coronary artery thrombi. The effect of a melanoma cell derived tissue-type plasminogen activator was studied in cat myocardium rendered ischemic by coronary artery ligation for 2 hours and reperfused for another 4 hours. Plasminogen activator was infused at a rate of 500 IU X kg-1 X min-1 for the first 30 minutes of reperfusion. The marked increase in plasma creatine kinase activity during reperfusion was significantly lower in plasminogen activator-treated cats at 4, 5 and 6 hours, with 7.7 +/- 1.5 X 10(-3) IU X mg protein-1 (n = 8) in the plasminogen activator group versus 17.8 +/- 3.5 X 10(-3) IU X mg protein-1 (n = 7) in the vehicle group at 6 hours (mean +/- SEM). The area at risk in the two ischemic groups was not different, being 14.6 +/- 1.5 and 16.6 +/- 1.4% of total left ventricular mass for the treated and untreated groups, respectively. However, the mass of necrotic tissue determined histochemically was significantly lower in the plasminogen activator-treated group, accounting for 29.5 +/- 3.9% of the area at risk compared with 46.8 +/- 4.2% of area at risk in cats receiving only the vehicle (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086418 TI - New mechanisms of action for tissue-type plasminogen activator? PMID- 3086419 TI - Development of an iron checklist to guide food intake. AB - An iron checklist comprised of 93 foods was developed to evaluate food choices in terms of iron concentration or frequency of use and to incorporate principles of iron nutriture. The instrument was tested with 89 Expanded Food and Nutrition Education Program technicians. The correlation between points scored on the iron checklist and milligrams of iron calculated from the same 24-hour recall was 0.77. Analyzing iron points by food group highlighted the fact that half of the group had not consumed milk foods and half of the group was receiving 6 to 18 mg iron from the meat group. Seventy-five percent of the sample improved their knowledge of iron foods by using the checklist to assess their diets and to identify food sources of iron. In comparison with the use of a computer, use of the iron checklist was shown to be cost-effective for assessing, teaching, and evaluating program outcomes. PMID- 3086420 TI - Use of silicone fluids in studies of cellular amino acids. AB - In numerous cellular studies, cells labeled with radioisotopes have been separated from the labeling medium by an aqueous solution in order to determine the quantity of internalized labels; however, the aqueous wash tends to remove significant labeling from the cells. Therefore, in order to preserve all of the internalized labels, non-aqueous medium such as silicone fluids may be used. The termination of the labeling is achieved in the silicone method when, upon centrifugation, the cells separate from the medium and enter the silicone fluid to sediment to the tube bottom. This sedimentation of cells placed above a layer of silicone fluid exhibits a critical dependence on the centrifugal force, and gives rise to an uncertainty of only 2 s in determining the time of separation of cells from the medium using General Electric F-50 silicone fluid and a modified Beckman J2-21 centrifuge. It is therefore possible to determine the kinetics of incorporation of labeled amino acids into intracellular pools and proteins. In particular, since this silicone wash method determines the size of the total pool and the aqueous wash method determines the size of the acid-extractable pool, the simultaneous measurements of the size of both pools leads to the determination of the kinetics of labeling of the free amino acid pool. Among many possible applications and extensions of these methods, the studies of formation of intracellular pools and relations among different pools of transported molecules, such as water and amino acids, appear promising. PMID- 3086421 TI - The determination of binding constants with a differential thermal and potentiometric titration apparatus. II. EDTA, EGTA and calcium. AB - A differential pH and thermal titrimeter has been used to determine the ionization constants of EDTA and EGTA as well as their calcium complexes. The intrinsic heat of binding is a constant for the pH range 2-11.5 for both substances and is found to be -5.4 kcal mol for EDTA and -7.9 kcal mol-1 for EGTA. The binding constants evaluated by fitting to the potentiometric curves and expressed as the log are 10.25 and 11.0, respectively. These values compare reasonably well to those reported in the literature. We have proposed that the binding of calcium occurs even at acid pH based on the pH drop observed at pH 2 when calcium is added, the reversibility of the thermal and the potentiometric curves, the lack of hysteresis upon rapid titration, the constancy of the intrinsic heat of binding and fitting of the entire potentiometric curves using the appropriate binding constants. PMID- 3086422 TI - Effects of obesity on gonadotropin secretion in patients with polycystic ovarian disease. AB - To investigate the interrelationships between body weight and gonadotropin secretion of polycystic ovarian disease (PCO), basal hormonal pattern and responses of gonadotropins and 17 beta estradiol (E2) to 25 micrograms (bolus) and 175 micrograms (4-h infusion) of synthetic luteinizing hormone-releasing hormone (LHRH) were studied in two age-matched groups of 18 obese (OB-PCO) and 18 normal-weight (NO-PCO) women suffering from the syndrome. Unlike other hormone levels, plasma LH and the LH/FSH ratio values were significantly higher (p less than 0.001) in NO-PCO than in OB-PCO females. Moreover, LH response to both stimuli was significantly greater in NO-PCO with respect to OB-PCO. No differences were found in FSH response, whereas E2 response was significantly higher (p less than 0.05) in the NO-PCO group during the continuous infusion test. These results emphasize the role of body weight in the development of PCO in obese females. PMID- 3086424 TI - A model for change in long-term care. PMID- 3086423 TI - Serum thyrotropin by ultrasensitive immunoradiometric assay and serum free thyroid hormones in pregnancy. AB - Variations of serum TSH, measured by an ultrasensitive immunoradiometric assay, of serum total and free thyroid hormones and of thyroxine-binding globulin (TBG) and sex hormone-binding globulin (SHBG) were investigated in a group of 18 normal women before and during pregnancy. A gradual increase of total thyroid hormones, TBG and SHBG was observed, while mean serum free thyroxine and free triiodothyronine progressively decreased. Serum TSH concentrations were comprised within the normal range throughout pregnancy, although a small but significant increase was found in the 2nd and 3rd trimester. These changes may represent a compensatory mechanism to meet the increased demand for thyroid hormones in pregnancy and must be taken into account for a correct evaluation of thyroid function during gestation. PMID- 3086425 TI - Development of a synthetic replacement for the flexor tendon pulleys--an experimental study. AB - A method was developed to reconstruct the fibro-osseous pulleys with Nitex, a synthetic material. Nitex is a closely woven fabric constructed from monofilament nylon fibers. Six adult monkeys (24 digits) had excision of the A1 and A2 pulleys; this was followed by reconstruction of the A2 pulley with the Nitex synthetic material. The animals were killed, two at a time, at 4, 8, and 12 weeks to evaluate the effectiveness of the Nitex pulleys. Flexor tendon function was assessed by biomechanical methods with a tensile testing machine to measure the tendon excursion and the work of flexion (the area under the force-excursion curve) necessary to fully flex each digit; these parameters revealed that the Nitex pulleys were capable of preventing tendon bow-stringing and did not significantly impair tendon gliding. The breaking strength of the Nitex pulleys was comparable to that of normal A2 pulleys (for monkeys weighing less than 10 kg) and it was sufficient to allow immediate mobilization of the digits postoperatively without fear of pulley rupture. Histologic examination showed minimal foreign body reaction around the Nitex, and the gliding surface of a Nitex pulley was found to be covered with a smooth layer of fibrous tissue with minimal adhesions to the underlying flexor tendon. The synthetic Nitex pulley appears to have the potential to function as an effective fibro-osseous pulley replacement. PMID- 3086427 TI - Primary invasive aspergillosis of the hand. AB - Primary invasive aspergillosis of the hand is an unusual manifestation of an opportunistic fungal infection that affects children who receive induction chemotherapy for acute leukemia. The surgeon should maintain a high index of suspicion when evaluating even the most innocuousappearing hand lesion in an immunocompromised patient. Early diagnosis, intravenous amphotericin B, and radical surgical debridement may prevent angioinvasion and subsequent fatal widespread dissemination. PMID- 3086426 TI - The effect of flexor sheath integrity on nutrient uptake by primate flexor tendons. AB - The effect of flexor sheath excision versus sheath incision and repair on the uptake of 3H-proline by profundus tendons in zone II was examined. Proline uptake was measured at 7 days in eight monkeys with intact flexor tendons (group I) and at either 3 or 7 days in eight monkeys with the tendons transected and repaired (group II). In both groups, the flexor sheaths of the digits of the right hand were excised, whereas those of the left hand were incised and repaired. For both the intact and the transected and repaired flexor tendons, it was found that 3H proline uptake was not improved with sheath closure. The extracellular tissue fluid appeared to be capable of providing nutrients to the tendon in amounts equal to that of the synovial fluid. Therefore, closure of the sheath after primary flexor tendon repair does not appear to be necessary for tendon nutrition, according to the data obtained from experimental studies on the nonhuman primate. PMID- 3086428 TI - A simple trypsin resistance assay for muscle and other cell fusion. AB - Muscle cells fusing in vitro have long provided biologists with a tool to study development and gene expression. However, many such studies used morphological assays of cell fusion. We present here a method for assaying fusion at a specific, operationally defined step. Muscle cells grown in monolayer are exposed to trypsin-EDTA solution at 37 degrees C; the trypsin is inactivated, the cells fixed in Lugol's iodine, and 200 to 300 nuclei are counted as being single or multiple. The presence of EDTA is important under standard conditions for muscle culture; however, little difference is seen in divalent cation-depleted cultures. Therefore, for consistency EDTA can be included in all assays. Samples are stable for over 24 hr, with no cell loss from trypsinization or fixation. This assay exploits a specific stage of muscle fusion, trypsin-resistant contact, to provide a rapid, simple, and observer-independent assay for an early state of muscle fusion. The assay can be used to measure fusion between any nucleated cells. PMID- 3086429 TI - H2-restricted recognition of cloned HLA class I gene products expressed in mouse cells. AB - Long-term syngeneic mouse cytolytic T lymphocyte (CTL) clones were obtained from DBA/2 (H2d) mice immunized with P815 (H2d) cells transfected with cloned human class I histocompatibility genes, HLA-CW3 or HLA-A24. Three distinct patterns of specificity were defined on P815 HLA transfectant target cells. One clone lysed HLA-CW3 but not -A24 transfectants, and a second lysed HLA-A24 but not -CW3 transfectant target cells. The third clone lysed P815 targets transfected with either HLA gene. None of the CTL clones lysed L cells (H2k) transfected with the same HLA genes or human targets that expressed these HLA specificities. Several lines of evidence indicated that recognition of HLA transfectants by these CTL clones was H2 restricted. First, lysis of P815 HLA transfectants could be inhibited by anti-H2Kd monoclonal antibody. In addition, the anti-P815-HLA CTL clones could lyse a (human X mouse) hybrid target that expressed both HLA class I and H2Kd antigens, but not a clonal derivative that no longer expressed H2Kd. The most direct evidence for H2-restricted recognition of P815-HLA transfectants by the syngeneic CTL clones was obtained by double transfection of mouse L cells (H2k) with both HLA and H2 class I genes. L cells transfected with HLA and H2Kd genes were susceptible to lysis by the same CTL clones that lysed the corresponding P815-HLA transfectant targets. Thus under certain conditions, CTL recognition of xenogeneic class I histocompatibility gene products can be restricted by other class I gene products. PMID- 3086430 TI - Treatment of established chronic relapsing experimental allergic encephalomyelitis with anti-L3T4 antibodies. AB - CR-EAE is an autoimmune T cell-mediated disease that can be induced in mice either by the injection of MSCH and CFA or by passive transfer of MBP-sensitized T cells. To evaluate the clinical relevance of anti-L3T4 antibodies in this relapsing, remitting disease, we studied the therapeutic benefits of such treatment on CR-EAE in animals when treatment was begun after the onset of initial paralytic signs. Animals treated biweekly with anti-L3T4 antibody had fewer relapses than control animals, and the histopathology of the brain and spinal cord showed fewer and less extensive lesions. Serial analysis of lymph node cell populations and antibody levels showed that animals treated with anti L3T4 antibody had a depletion of the helper/inducer T cell population and did not develop a humoral response to the administered rat antibody. This study raises the possibility of treatment with antibodies against T cell subsets in established disease wherein this subset is known to play a crucial role. PMID- 3086431 TI - HD39 (B3), a B lineage-restricted antigen whose cell surface expression is limited to resting and activated human B lymphocytes. AB - The B cell-restricted antigen HD39, whose cell surface expression is limited to resting and activated human B lymphocytes, is described in this report. The monoclonal antibody HD39 detects a two-chain glycoprotein with apparent molecular weights of 130,000 and 140,000. During B cell ontogeny, HD39 is first expressed in the cytoplasm of bone marrow derived pre-B cells, then appears on the cell surface of sIgM+ B cells, and finally on the majority of sIgM+ sIgD+ resting B cells. After activation in vitro, the expression of HD39 on the cell surface first increases, and then the antigen is lost as cells begin to differentiate. HD39 is weakly expressed on very few non-T cell ALL and B cell CLL, on approximately 50% of B cell lymphomas, and not on Waldenstrom's macroglobulinemias and myelomas. In contrast, it is strongly expressed on all hairy cell leukemias. Its limited cell surface expression in B cell ontogeny suggests that HD39 may be important in the events that regulate the activation of the human resting B lymphocytes. PMID- 3086432 TI - The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. AB - We examined the antigenic and functional characteristics of human peripheral blood lymphocytes that differentially express the CD16 (Leu-11) and Leu-19 (NKH 1) antigens. Leu-19 is a approximately 220,000 daltons protein expressed on approximately 15% of freshly isolated peripheral blood lymphocytes. Within the Leu-19+ subset, three distinct populations were identified: CD3-,CD16+,Leu-19+ cells; CD3+,CD16-,Leu-19+ cells; and CD3-,CD16-,Leu-19bright+ cells. Both the CD3+,CD16-,Leu-19+ and CD3-,CD16+,Leu-19+ populations mediated non-major histocompatibility complex (MHC)-restricted cytotoxicity against the NK-sensitive tumor cell K562 and were large granular lymphocytes. CD3-,CD16+,Leu-19+ NK cells were the most abundant (comprising approximately 10% of peripheral blood lymphocytes) and the most efficient cytotoxic effectors. The finding that CD3+,Leu 19+ lymphocytes mediated cytotoxicity against K562 unequivocally demonstrates that a unique subset of non-MHC-restricted cytotoxic CD3+ T lymphocytes are present in the peripheral blood of unprimed, normal individuals. However, CD3+,CD16-,Leu-19+ cells comprised less than 5% of peripheral blood lymphocytes, and the cytotoxic activity of this subset was significantly less than CD3-,CD16+,Leu-19+ NK cells. Most CD3+,Leu-19+ T cells co-expressed the CD2, CD8, and CD5 differentiation antigens. The antigenic and functional phenotype of peripheral blood CD3+,Leu-19+ cytotoxic T lymphocytes corresponds to the interleukin 2-dependent CD3+ cell lines that mediate non-MHC-restricted cytotoxicity against NK-sensitive tumor cell targets. A small population of Leu 19bright+ lymphocytes lacking both CD3 and CD16 was also observed. This population (comprising less than 2% of peripheral blood lymphocytes) contained both large agranular lymphocytes and large granular lymphocytes. CD3-,CD16-,Leu 19bright+ lymphocytes also mediate non-MHC-restricted cytotoxicity. The relationship of these CD3-CD16-,Leu-19bright+ lymphocytes to CD3+ T cells or CD16+ NK cells is unknown. PMID- 3086434 TI - Expression of interleukin 2, interferon-gamma, and the IL 2 receptor by human peripheral blood lymphocytes. AB - Human peripheral blood T lymphocytes were treated with recombinant interleukin 2, mitogens, and dexamethasone. The resulting accumulation of mRNA for interleukin 2 (IL 2), the interleukin 2 receptor (IL 2R), and interferon-gamma (IFN-gamma) was measured. IL 2 was found to regulate the levels of each of these mRNA. The expression of mRNA for IL 2, IL 2R, and IFN-gamma correlated very well with the levels of protein observed. In populations of peripheral blood T lymphocytes, the production of IL 2 and IFN-gamma were not necessarily coordinately expressed. The sequential expression of these mRNA was investigated in order to determine whether they might be independent of the action of IL 2. IFN-gamma and IL 2 mRNA showed biphasic accumulations. IL 2 mRNA accumulated very rapidly, within 60 min after mitogen stimulation and before any detectable IL 2R mRNA accumulation. Similarly, IFN-gamma mRNA accumulated rapidly, simultaneously with IL 2 mRNA. This early peak of IFN-gamma mRNA, therefore, is likely to be independent of IL 2 action. Both IL 2 and IFN-gamma mRNA then showed later peak times of accumulation. IL 2 mRNA levels peaked at 5 hr after mitogen stimulation, whereas IFN-gamma mRNA levels peaked at 20 hr. IL 2R mRNA continued to accumulate for the full 40 hr of these kinetic experiments. The later accumulations of IFN-gamma and IL 2R mRNA and the resulting expression of the corresponding proteins may therefore be dependent on the earlier production of IL 2 and its subsequent interaction with the IL 2R on the surface of such activated T cells. PMID- 3086433 TI - The suppressive influences of human tumor necrosis factors on bone marrow hematopoietic progenitor cells from normal donors and patients with leukemia: synergism of tumor necrosis factor and interferon-gamma. AB - The influences of human tumor necrosis factor (TNF) (LuKII), recombinant human TNF-alpha, natural human interferon-gamma (HuIFN-gamma), recombinant HuIFN-gamma, and natural HuIFN-alpha were evaluated alone or in combination for their effects in vitro on colony formation by human bone marrow granulocyte-macrophage (CFU GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells incubated at 5% CO2 in lowered (5%) O2 tension. TNF (LuKII) and recombinant TNF-alpha caused a similar dose-dependent inhibition of colony formation from CFU-GM, BFU E, and CFU-GEMM. Day 7 CFU-GM colonies were more sensitive than both day 14 CFU GM colonies and day 7 CFU-GM clusters to inhibition by TNF. BFU-E colonies and CFU-GEMM colonies were least sensitive to inhibition with TNF. The suppressive effects of TNF (LuKII) and recombinant TNF-alpha were inactivated respectively with hetero-anti-human TNF (LuKII) and monoclonal anti-recombinant human TNF alpha. The hetero-anti-TNF (LuKII) did not inactivate the suppressive effects of TNF-alpha and the monoclonal anti-recombinant TNF-alpha did not inactivate TNF (LuKII). The suppressive effects of TNF did not appear to be mediated via endogenous T lymphocytes and/or monocytes in the bone marrow preparation, and a pulse exposure of marrow cells with TNF for 60 min resulted in maximal or near maximal inhibition when compared with cells left with TNF for the full culture incubation period. A degree of species specificity was noted in that human TNF were more active against human marrow CFU-GM colonies than against mouse marrow CFU-GM colonies. Samples of bone marrow from patients with non-remission myeloid leukemia were set up in the CFU-GM assay and formed the characteristic abnormal growth pattern of large numbers of small sized clusters. These cluster-forming cells were more sensitive to inhibition by TNF than were the CFU-GM colonies and clusters grown from the bone marrow of normal donors. The sensitivity to TNF of colony formation by CFU-GM of patients with acute myelogenous leukemia in partial or complete remission was comparable with that of normal donors. When combinations of TNF and HuIFN were evaluated together, it was noted that TNF (LuKII) or recombinant TNF synergized with natural or recombinant HuIFN-gamma, but not with HuIFN-alpha, to suppress colony formation of CFU-GM, BFU-E, and CFU GEMM from bone marrow of normal donors at concentrations that had no suppressive effects when molecules were used alone.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3086435 TI - Bacterial lipopolysaccharide-induced interferon-gamma production: roles of interleukin 1 and interleukin 2. AB - Bacterial lipopolysaccharide (LPS) induced human peripheral blood mononuclear cells (PBMC) to produce interferon-gamma (IFN-gamma). Monocytes play a mandatory accessory role in this process, because purified T lymphocytes failed to produce IFN-gamma in response to LPS and the addition of 2% monocytes to T cell cultures resulted in an optimal LPS-induced IFN-gamma production. IFN-gamma production was abolished in the presence of monoclonal antibodies specific for HLA-DR antigen. Addition of exogenous interleukin 2 (IL 2) markedly enhanced IFN-gamma secretion by PBMC induced with LPS. The addition of anti-Tac antibody specific for IL 2 receptors abrogated IFN-gamma production, suggesting that an interaction of IL 2 with IL 2 receptors was involved. By using a specific antibody binding assay, LPS was shown to amplify IL 2 receptor expression on PBMC, whereas exogenous IL 2 showed only a negligible enhancing effect on the expression of its own receptors. Interleukin 1 (IL 1), a product of LPS-stimulated monocytes, potentiated IL 2 induced IFN-gamma production in the absence of LPS. Neither IL 1 nor IL 2 alone induced IFN-gamma production in purified T lymphocyte cultures. When added together, however, substantial levels of IFN-gamma were induced. An enhanced IL 2 receptor expression on T cells was also demonstrated as a result of the combined action of IL 1 and IL 2. These results suggest that induction of IFN-gamma by LPS is due mainly to the generation of IL 1 and an enhanced expression of IL 2 receptors. PMID- 3086436 TI - Administration of monoclonal anti-T cell antibodies retards murine lupus in BXSB mice. AB - Murine lupus in BXSB mice is associated with B cell hyperactivity, monocyte proliferation, and impaired T cell function. However, the significance of these abnormalities, and the relationship among them, has not been clearly established. To examine the role of T cells in the pathogenesis of autoimmune disease in BXSB mice, we depleted specific T cell subsets from BXSB males by using rat IgG2b monoclonal antibodies (MAb) to either Thy-1.2 (on all T cells) or L3T4 (on "helper/inducer" T cells). A single injection of anti-Thy-1.2 (6 mg i.v.) at age 3 mo produced a sustained 40 to 50% reduction in circulating T cells for 6 mo. Treatment prevented monocytosis, reduced anti-DNA antibody concentration, and retarded renal disease, but it did not prolong life. Repeated injections of rat MAb to Thy-1.2 were precluded by the development of a host immune response to rat immunoglobulin (Ig) that can cause anaphylaxis in BXSB mice. In contrast, rat MAb to L3T4 stimulated little or no immune response to rat Ig. We therefore were able to treat BXSB mice weekly with anti-L3T4 (2 mg i.p.) from age 3 to 12 mo. Treatment reduced circulating L3T4+ cells beneath the level of detection by fluorescence analysis. It also significantly reduced monocytosis, anti-DNA antibody production, renal disease, and mortality. These findings establish that monocytosis and autoimmunity in BXSB mice are promoted by T cells. They extend our previous observation that MAb to L3T4 retard autoimmunity in NZB/NZW F1 mice. Our finding that treatment with MAb to L3T4 is effective in two strains of lupus prone mice suggests that treatment with MAb to Leu-3/T4, the human homologue for L3T4, may be effective in people with systemic lupus erythematosus. PMID- 3086437 TI - Cloning, sequence, and expression of bovine interferon-gamma. AB - Bovine interferon-gamma (IFN-gamma) sequences have been isolated by screening a cDNA library with a human IFN-gamma cDNA probe. The cDNA library was constructed from RNA isolated from concanavalin A-stimulated bovine lymph node cells. The open reading frame predicts that the bovine IFN-gamma precursor is composed of 166 amino acids with a predicted m.w. of 19,393. Alignment of the amino acid sequence with human IFN-gamma indicates that mature bovine IFN-gamma is composed of 143 amino acids with a predicted m.w. of 16,858. It has an amino acid homology of 63% with human IFN-gamma, and 47% with murine IFN-gamma. Biologically active bovine IFN-gamma was synthesized in an Escherichia coli expression system. PMID- 3086438 TI - Release of arachidonic acid and formation of oxygenated derivatives after complement attack on macrophages: role of channel formation. AB - Treatment of [3H]arachidonic acid ([3H]C20:4)-labeled, antibody-sensitized mouse resident peritoneal macrophages with rabbit serum complement, or C6-deficient rabbit serum + C6, caused hydrolytic release of incorporated [3H]C20:4 from phospholipids, followed by conversion to oxygenated derivatives. The C6 dose response curve for release of C20:4 plus its metabolites was monotonic, which indicates dependence on channel formation, whereas the dose-response curve for lysis displayed multi-hit behavior. High-performance liquid chromatography demonstrated that the major radiolabeled products in the aqueous phase co-eluted with C20:4, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and prostaglandin E2. Kinetic studies of the release of 6-keto-PGF1 alpha, the major metabolite, displayed biphasic characteristics; a moderate amount of this prostaglandin was released before the onset of cell lysis. Experimental evidence obtained by freeze thaw or by incubation of these cells with melittin or A23187 indicated that cell lysis does not necessarily result in the production of inflammatory mediators. Furthermore, when macrophages were treated with serum complement, it was apparent that the major part of the release was due to C5b-9 and not to the action of C5a. We conclude that release of C20:4 and its derivatives from complement-treated macrophages does not depend on cytolysis, but is a consequence of insertion and channel formation. PMID- 3086439 TI - Identification of Schistosoma mansoni glycoproteins recognized by protective antibodies from mice immunized with irradiated cercariae. AB - The humoral immune responses of mice patently infected with Schistosoma mansoni and of mice vaccinated with radiation-attenuated cercariae were compared by radioimmunoassays and one- and two-dimensional polyacrylamide gel analyses of radioimmunoprecipitates. The binding observed with antibodies of mice vaccinated twice with radiation-attenuated cercariae over a period of 7 to 11 wk was less than 50% of the binding observed with antibodies of mice patently infected for 20 wk, but three to four times greater than that obtained with antibodies of mice infected for 6 wk, irrespective of whether the test antigen extracts were derived from schistosomula or adult worms. Sera of vaccinated mice precipitated a restricted number of predominantly high m.w. glycoproteins of both schistosomula and adult worms metabolically labeled with [35S] methionine. Each of the glycoproteins of 36 hr in vitro-cultured schistosomula that was precipitated by the sera of vaccinated mice was also precipitated by sera of infected mice. In contrast, sera of vaccinated mice uniquely precipitated a 38,000 m.w. glycoprotein of schistosomula cultured for 5 days and a 94,000 m.w. glycoprotein of adult male worms. Although radiation-attenuated larvae do not reach the adult stage, mice vaccinated with these still elicit a strong immune response against egg glycoproteins. In particular, an egg glycoprotein of 85,000 to 70,000 and isoelectric point of 4.8 showed an enhanced reactivity with sera of vaccinated mice in comparison with infected mice. These results show that the antibody response in mice vaccinated with radiation-attenuated larvae differs qualitatively and quantitatively from that of infected mice. PMID- 3086440 TI - Clonal relationship of the lymphoblastic cell line P388 to the macrophage cell line P388D1 as evidenced by immunoglobulin gene rearrangements and expression of cell surface antigens. AB - A lymphocytic tumor of early B cell lineage, P388, and a mature macrophage tumor, P388D1, appear to have been derived from a common precursor based on identical immunoglobulin gene rearrangements and shared cell surface antigens. These cell lines may have resulted from differential maturation of a transformed cell that is an immediate cellular precursor to both the B cell and myeloid lineages. This supports earlier findings that suggest a close relationship between early B cell and myeloid differentiation pathways. PMID- 3086441 TI - Antigenic modulation by anti-CD5 immunotoxins. AB - We evaluated the modulation of T101 immunotoxins (IT) and free T101 antibody from the surface of normal and leukemic cells to determine whether the presence of toxin on antibody affected antigenic modulation. Reagents were made by conjugating T101, which binds to the T cell antigen CD5, to either intact ricin or purified ricin A chain. We found that T101-A chain modulated CD5 more efficiently than T101-ricin, which modulated CD5 more efficiently than T101 alone. Kinetic studies showed that maximal modulation of IT was reached within 3 hr. When toxicity of the reagents was tested in protein synthesis inhibition assays, T101-ricin in the presence of lactose inhibited 99% of the protein synthesis of CEM cells. T101-A chain was less toxic, inhibiting protein synthesis only 23 to 43%. The addition of the potentiating agent monensin nearly doubled the toxicity of T101-A chain, but did not affect T101-A chain modulation. To determine the fate of bound IT, T101 and T101-ricin were labeled with 125I. Cells were incubated under modulating conditions in the presence of radiolabeled reagents. T101 and T101-ricin were internalized into CEM cells. In contrast, T101, but not T101-ricin, appeared to be shed from peripheral blood mononuclear cells. Our findings show clearly that: 1) the presence of toxin on antibody does not inhibit--and may actually enhance--modulation; 2) T101-IT are internalized, not shed from the cell surface; 3) the lack of toxicity of T101-A chain is not attributed to inability to modulate; 4) there is no correlation between enhancement of T101-A chain toxicity by monensin and antigenic modulation by A chain reagents; and 5) modulation, which is undesirable in monoclonal antibody therapy, may be advantageous in the therapeutic use of IT. PMID- 3086442 TI - In vivo and in vitro expression of macrophage membrane interleukin 1 in response to soluble and particulate stimuli. AB - We examined the expression of a membrane form of interleukin 1 (IL 1) by macrophages. Murine peritoneal macrophages fixed immediately after harvesting, in suspension, did not show membrane IL 1. Membrane IL 1 was expressed after a 3-hr culture on plastic dishes. These findings allowed us to examine some conditions in vivo that may trigger the expression of this protein; that is, by fixing the macrophages in suspension we could determine if a given stimulus had an effect. We found that membrane IL 1 was expressed briefly after administration of live or dead Listeria monocytogenes or endotoxin. Serum proteins were ineffective. At the time of maximal activation of macrophages by live Listeria, membrane IL 1 was not expressed. Analysis of in vitro conditions indicated that expression of membrane IL 1 and Ia molecules could be dissociated. In culture, recombinant interferon gamma induced Ia but no membrane IL 1. Uptake of dead Listeria organisms had no effect on Ia but triggered membrane IL 1. The stimulation of membrane IL 1 was not caused by phagocytosis per se: latex particles were ineffective. Opsonized red cells stimulated membrane IL 1 on macrophages that were activated in vivo by inflammatory stimuli. PMID- 3086443 TI - The role of nonactivated and interferon-gamma activated monocytes in regulating normal and SLE patient B cell responses to TNP-Brucella abortus. AB - We have previously characterized the human B cell response to trinitrophenol (TNP)-Brucella abortus (Ba) response as being T cell independent. In this report we examine the role of monocytes in the TNP-Ba antibody response of human peripheral blood mononuclear cells (PBMC). Depletion of monocytes by sequential adherence to plastic and Sephadex G-10 passage did not result in decreased plaque forming cell responses to TNP-Ba, suggesting that monocytes were not required. On the contrary monocytes were probably inhibitory because their removal resulted in enhanced responses. This was confirmed by showing that adding monocytes back reconstituted the inhibition. When interferon-gamma (IFN-gamma), a potent activator of monocytes, was added to TNP-Ba-driven PBMC cultures, marked inhibition (greater than 90%) of the responses ensued. This IFN-gamma-mediated suppression was monocyte dependent because it was completely abrogated by monocyte, but not T cell depletion. Previously, we described a concanavalin A (Con A), T cell inhibition pathway of the TNP-Ba response. Both the Con A and IFN gamma pathways were tested for their ability to inhibit systemic lupus erythematosus (SLE) patient responses to TNP-Ba. The B cell response of SLE patients was inhibitable by both pathways. In all of the patients, the inhibition was complete (greater than 95%) when IFN-gamma was added to the cultures. In the presence of Con A, greater than 95% inhibition was observed in six of 10 patients, the remainder being inhibited to a lesser extent. Thus the hyperactive B cells from SLE patients can be down-regulated, particularly in the presence of IFN-gamma. PMID- 3086444 TI - Expression of three cross-reactive idiotypes on rheumatoid factor autoantibodies from patients with autoimmune diseases and seropositive adults. AB - Approximately one-half of human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors (RF] from unrelated individuals with cryoglobulinemia coordinately express three cross-reactive idiotypic antigens (CRI). The CRI are detected with: 1) monoclonal antibody 17.109, which recognizes a conformation dependent CRI on K-light chains; and 2) two rabbit anti-peptide antibodies that react with primary sequence-dependent CRI (PSL2 and PSL3) corresponding to the conserved second and third K-chain complementarity-determining regions, respectively. In the present experiments, the structural features of polyclonal RF autoantibodies from diverse patients with rheumatoid arthritis and from those with primary Sjogren's syndrome, and from seropositive elderly subjects without overt autoimmune diseases, were investigated with these three defined anti-CRI reagents. The pattern of expression of the CRI differed among patient groups. Only the RF autoantibodies from Sjogren's syndrome patients frequently displayed all three CRI. However, the RF from nearly every subject tested, including patients with rheumatoid arthritis, were enriched in the primary sequence dependent PSL2-CRI as compared to RF-depleted Ig from the same subjects. Amino acid sequence analysis of monoclonal IgM-RF indicates that PSL2-CRI-positive light chains probably represent the products of a single Vk gene. Therefore, a proportion of the polyclonal RF from different autoimmune states may represent somatic variants of this germ-line RF Vk gene which retain the PSL2 sequence as a common element. PMID- 3086445 TI - Idiotypic analysis of a B cell clone with anti-intermediate filament specificity in a patient with Sjogren's syndrome: involvement of five subpopulations producing different immunoglobulin isotypes. AB - An IgM paraprotein from patient LP with Sjogren's syndrome exhibited an antibody activity to intermediate filaments (IMF) of cells from all vertebrates examined, and appeared to recognize several classes of IMF (i.e., vimentin, desmin, and keratin). A mouse monoclonal anti-idiotype (Id) antibody, K4A, was prepared against the IgMk (LP) and used as a specific probe in two-color immunofluorescence to examine the extent of clonal involvement in the patient's blood and bone marrow mononuclear cells (MNC). Twenty to 30% of MNC in her blood samples were IgMk+ plasmablasts with morphologic similarity to Waldenstrom's macroglobulinemia cells. IgG+ and IgA+ plasmablasts were demonstrated in lower frequencies (approximately 2%). Almost all of the IgM+ cells and approximately 80% of the IgG+ cells and IgA+ cells in the blood were reactive with the K4A anti Id antibody. Immunoglobulin (Ig) subclass analysis revealed that the K4A Id was expressed by IgG1+, IgG3+, IgA1+ and IgA2+ plasmablasts. Similar observations were obtained with bone marrow samples, although the proportion of Id+ cells among IgG+ or IgA+ cells was lower in marrow than in blood. IgG and IgA fractions isolated from the patient's serum were also shown to contain anti-IMF activity. Ig biosynthetic analysis of blood MNC revealed that the K4A anti-Id antibody precipitated not only IgM but also IgG and IgA. Because cells simultaneously producing two different Ig isotypes were not detected, these results indicate the presence of five separate subpopulations of the K4A Id+ neoplastic clone. The data thus suggest the occurrence of a neoplastic or pre-neoplastic transformation event before the switching of Ig heavy chain isotypes, and imply a role for the IMF antigen in the exaggerated proliferation and differentiation along five of the nine potential intraclonal pathways. PMID- 3086446 TI - Interleukin 2 receptors on cultured murine epidermal Langerhans cells. AB - Rat monoclonal antibodies 3C7 and 7D4 detect two distinct functional regions of the murine interleukin 2 (IL 2) receptor. When studying the emergence kinetics of IL 2 receptors in mixed epidermal cell (EC)-lymphocyte cultures by using 3C7 and 7D4 in an indirect immunofluorescence assay, we regularly encountered a distinctive membrane fluorescence not only on lymphocytes, but also on a subpopulation of cells exhibiting a dendritic morphology. Reasoning that these 3C7/7D4-reactive dendritic cells might represent a subpopulation of epidermal dendritic cells, we studied mouse EC for the presence of 3C7/7D4- reactive cells. Although 3C7/7D4 reactivity was never detected on freshly isolated EC or on epidermal sheets, a small number of 3C7/7D4+ cells was encountered after 24 to 48 hr of culture. These cells exhibited a dendritic shape, expressed Ia antigens, lacked Thy-1 antigens, and displayed the ultrastructural features of Langerhans cells (LC) with the notable exception of Birbeck granules. Although after 24 hr, only 20% of Ia+ EC were 3C7/7D4+, the vast majority of LC displayed 3C7/7D4 binding sites after 4 to 5 days of culture. Preincubation of cultured LC-enriched EC with recombinant human IL 2 prevented subsequent 3C7-but not 7D4-binding to these cells. Western blot analysis of 7D4-reactive material of detergent extracts from LC-enriched EC revealed three bands in the same m.w. range as reported for CTLL cells. These results demonstrate that cultured LC express IL 2 receptors and may bear important implications for a better understanding of growth regulation, differentiation, and immunologic functions of LC. PMID- 3086447 TI - The augmentation of human natural killer cell activity by interferon-gamma is not associated with the induction of the interferon-alpha-inducible proteins. AB - Treatment of partly purified large granular lymphocytes (LGL) with either IFN alpha or IFN-gamma for 2 hr augmented their NK cell activity. This augmentation was completely inhibited by the addition of 10 micrograms/ml of cycloheximide. In contrast, when the effects of IFN-gamma on the synthesis of specific proteins in these cells was directly studied by use of two-dimensional gel electrophoresis, we found that IFN-gamma was unable to induce any of the earlier detected, IFN alpha/IFN-beta-inducible proteins within 18 hr of incubation. No additional, IFN gamma-induced proteins were detected in either the partly purified LGL or purified T cells. In contrast, the effects of the two factors were comparable in the glioma cell line 251 MG. This shows i) that the effects of IFN-alpha and IFN gamma are dependent on the responder cell type, ii) that there exists at least one mechanism that can augment NK cell activity that is not dependent on the increased synthesis of the IFN-alpha-inducible proteins, and iii) that either the nine IFN-alpha-inducible proteins are not involved in any leukocyte function that is augmentable by both IFN-alpha and IFN-gamma, or that the two factors exert their actions in leukocyte through different mechanisms. PMID- 3086448 TI - Cellular requirements for thyrotropin enhancement of in vitro antibody production. AB - We reported previously that thyrotropin (TSH) enhanced the in vitro antibody response to a T cell-dependent antigen, sheep red blood cells (SRBC), as determined by direct plaque-forming cell (PFC) assay. The present studies were designed to determine the possible immunoregulatory function of TSH on lymphocytes immunized with the T-independent antigen Brucella abortus-TNP (BA TNP) and the cellular components involved in such function. We report here that TSH enhanced the in vitro antibody response to BA-TNP as determined by direct PFC assays. Cell depletion studies showed that the TSH effect, although independent of macrophages, required the presence of T cells. Thus, pituitary--and possibly leukocyte--TSH appears to function as a lymphokine which may act via T cells to augment antibody production. PMID- 3086449 TI - Analysis of anti-streptococcal group A carbohydrate idiotope levels in sera: correlation of magnitude of expression with idiotope position and VK haplotype. AB - We have employed monoclonal anti-idiotopes to map the corresponding idiotopes on the variable domain of a prototype antibody specific for streptococcal group A carbohydrate (GAC). Idiotope variability, as assessed by direct and competitive binding assays, previously was shown to correlate with idiotope position; determinants farther from the binding site were less variable. We now describe a relationship between idiotope position and idiotope concentration in normal and GAC-immune sera from mice of several inbred and recombinant inbred strains. Employing sera as inhibitors in a competitive radioimmunoassay, we demonstrate that idiotopes farther from the binding site (more proximal) tend to be present at higher levels in GAC-hyperimmune sera. Only the most proximal idiotope was detected in normal serum, and this idiotope was present in normal sera from all 12 strains tested. Finally, significant interstrain differences in patterns of idiotope expression were observed, and some of these differences appear to be correlated with allelic differences at immunoglobulin structural gene loci. PMID- 3086450 TI - Protective effect of the membrane skeleton on the immunologic reactivity of the human red cell Rho(D) antigen. AB - It has recently been shown that the 30,000 m.w. Rho(D) protein is associated with the membrane skeleton of the human red cell. We have studied the effects of the membrane skeleton on the immunoreactivity of the Rho(D) antigen present in Rho(D)+ membranes. Solubilization of the membranes with the Triton X-100 detergent and centrifugation of the extracts showed that more than 90% of the immunoreactive Rho(D) antigen sedimented with the membrane skeleton structures. The skeleton-bound Rho(D) antigen could be solubilized by disruption of the skeleton in low ionic strength medium. The removal of the membrane skeleton structure before the solubilization of the membranes with detergent resulted in the inactivation of the majority of the Rho(D) antigen. The effect of the membrane skeleton on the stability of the Rho(D) antigen was additionally studied in detergent extracts prepared from native and skeleton-free membranes. The assay of the Rho(D) antigen activity in the extracts showed that the Rho(D) antigen was 100 times more sensitive to the detergent inactivation in skeleton-free membranes than in native membranes. These results indicate that the membrane skeleton is important for stabilizing the immunoreactive form of the Rho(D) protein on the red cell membrane. PMID- 3086451 TI - Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). AB - ICAM-1 is a cell surface glycoprotein originally defined by a monoclonal antibody (MAb) that inhibits phorbol ester-stimulated leukocyte aggregation. Staining of frozen sections and immunofluorescence flow cytometry showed intercellular adhesion molecule-1 (ICAM-1) is expressed on non-hematopoietic cells such as vascular endothelial cells, thymic epithelial cells, certain other epithelial cells, and fibroblasts, and on hematopoietic cells such as tissue macrophages, mitogen-stimulated T lymphocyte blasts, and germinal center dendritic cells in tonsils, lymph nodes, and Peyer's patches. ICAM-1 staining on vascular endothelial cells is most intense in T cell areas in lymph nodes and tonsils showing reactive hyperplasia. ICAM-1 is expressed in low amounts on peripheral blood leukocytes. Phorbol ester-stimulated differentiation of myelomonocytic cell lines greatly increases ICAM-1 expression. ICAM-1 expression on dermal fibroblasts is increased threefold to fivefold by either interleukin 1 (IL 1) or interferon-gamma at 10 U/ml over a period of 4 or 10 hr, respectively. The induction is dependent on protein and mRNA synthesis and is reversible. ICAM-1 displays Mr heterogeneity in different cell types with a Mr of 97,000 on fibroblasts, 114,000 on the myelomonocytic cell line U937, and 90,000 on the B lymphoblastoid cell JY. ICAM-1 biosynthesis involves a Mr approximately 73,000 intracellular precursor. The non-N-glycosylated form resulting from tunicamycin treatment has a Mr of 55,000. ICAM-1 isolated from phorbol myristic acetate (PMA) stimulated U937 and from fibroblasts yields an identical major product of Mr = 60,000 after chemical deglycosylation. ICAM-1 MAb interferes with the adhesion of phytohemagglutinin blasts, and the adhesion of the cell line SKW3 to human dermal fibroblast cell layers. Pretreatment of fibroblasts but not lymphocytes with ICAM 1 MAb, and of lymphocytes but not fibroblasts with lymphocyte function-associated antigen 1 MAb inhibits adhesion. Intercellular adhesion is increased by prior exposure of fibroblasts to IL 1, and correlates with induction of ICAM-1. PMID- 3086453 TI - Persistence of polyclonal B cell activation with undetectable parasitemia in late stages of experimental Chagas' disease. AB - The polyclonal B cell responses induced by Trypanosoma cruzi infection last for at least 6 mo after the inoculation of the parasites. In the acute phase of the disease, B cells from spleen and lymph nodes are largely stimulated, whereas a decrease in bone marrow PFC is observed. As the disease progresses, the numbers of Ig-secreting cells in the spleen, lymph nodes, and bone marrow are all enhanced. The isotype distribution of PFC, however, remains unvariable along the course of the infection, and it is characterized by the predominance of IgG2a- and IgG2b-secreting cells. No striking difference in the isotype pattern of resistant and susceptible strains of mice was observed. The continuous and long lasting B cell stimulation generated during the infection may have important consequences in the pathology of Chagas' disease. PMID- 3086452 TI - Intestinal mucosal mast cells from rats infected with Nippostrongylus brasiliensis contain protease-resistant chondroitin sulfate di-B proteoglycans. AB - Rats infected with the helminth Nippostrongylus brasiliensis were injected i.p. with 2 mCi of [35S] sulfate on days 13, 15, 17, and 19 after infection. The intestines were removed from animals on day 20 or 21 after infection, the intestinal cells were obtained by collagenase treatment and mechanical dispersion of the tissue, and the 35S-labeled mucosal mast cells (MMC) were enriched to 60 to 65% purity by Percoll centrifugation. The cell-associated 35S-labeled proteoglycans were extracted from the MMC-enriched cell preparation by the addition of detergent and 4 M guanidine HCl and were partially purified by density gradient centrifugation. The isolated proteoglycans were of approximately 150,000 m.w., were resistant to pronase degradation, and contained highly sulfated chondroitin sulfate side chains. Analysis by high-performance liquid chromatography of chondroitinase ABC-treated 35S-labeled proteoglycans from these rat MMC revealed that the chondroitin sulfate chains consisted predominantly of disaccharides with the disulfated di-B structure (IdUA-2SO4----GalNAc-4SO4) and disaccharides with the monosulfated A structure (G1cUA----GalNAc-4SO4). The ratio of disaccharides of the di-B to A structure ranged from 0.4 to 1.6 in three experiments. Small amounts of chondroitin sulfate E disaccharides (GlcUA--- GalNAc-4,6-diSO4) were also detected in the chondroitinase ABC digests of the purified rat MMC proteoglycans, but no nitrous acid-susceptible heparin/heparan sulfate glycosaminoglycans were detected. The presence in normal mammalian cells of chondroitin sulfate proteoglycans that contain such a high percentage of the unusual disulfated di-B disaccharide has not been previously reported. The rat intestinal MMC proteoglycans are the first chondroitin sulfate proteoglycans that have been isolated from an enriched population of normal mast cells. They are homologous to the chondroitin sulfate-rich proteoglycans of the transformed rat basophilic leukemia-1 cell and the cultured interleukin 3-dependent mouse bone marrow-derived mast cell, in that these chondroitin sulfate proteoglycans as well as rat serosal mast cell heparin proteoglycans are all highly sulfated, protease resistant proteoglycans. PMID- 3086454 TI - Immunogenicity of the repetitive and nonrepetitive peptide regions of the divergent CS protein of Plasmodium knowlesi. AB - The circumsporozoite (CS) protein of the Nuri strain of the simian malarial parasite Plasmodium knowlesi was expressed as a fusion protein in E. coli. This fusion protein cross-reacted with the polyclonal monkey sera raised against irradiated sporozoites of another strain (H strain) of P. knowlesi. The antibody against the repeat units of the H strain CS protein was affinity purified from the polyclonal sera by using synthetic repeat peptides. The affinity-purified antibody did not cross-react with the Nuri CS fusion protein. The immunogenicity of different regions of the CS protein was additionally studied by using several synthetic peptides. All but the most COOH-terminal peptide showed cross reactivity with the polyclonal sera. Because the repeat regions of the CS protein of the two strains are diverse, whereas the non-repetitive regions are immunogenic and conserved, the latter may be better suited for a potential vaccine. PMID- 3086455 TI - Structure of a class I gene from Syrian hamster. AB - Syrian hamsters possess a multigene class I family yet fail to perform several associative immunologic functions. In an attempt to determine whether representative hamster genes are structurally functional, we have cloned two closely linked class I-like genes and determined the complete sequence of the 5' member. Its exon organization is similar to that seen in mouse and man, although only two intracytoplasmic domains are encoded instead of the usual three. Comparison of the predicted amino acid sequence and the 3' untranslated region to mouse and human genes suggest along with the linkage data that the hamster gene may be related to either or both K and Qa region genes but probably not to D and L region genes. PMID- 3086456 TI - Regulation of macrophage Ia expression in mice with severe combined immunodeficiency: induction of Ia expression by a T cell-independent mechanism. AB - We have studied the expression of Ia molecules by macrophages from mice with severe combined immunodeficiency (CB-17 scid) that lack demonstrable T cell and B cell functions. CB-17 scid mice had approximately normal numbers of Ia-bearing macrophages in the peritoneal cavity, spleen, and liver. Peritoneal macrophages responded in culture to T cell-derived lymphokines with enhanced expression of Ia molecules. However, unlike immunocompetent controls, SCID mice could not enhance Ia expression in an antigen-specific T cell-dependent manner after secondary challenge in vivo with a conventional protein antigen such as hemocyanin. Further demonstration of their T cell deficiency was the failure of CB-17 scid spleen cells to proliferate and produce IL 2 in response to the T cell mitogen, concanavalin A. Upon infection with Listeria monocytogenes, CB-17 scid mice developed chronically high loads of bacteria, whereas CB-17 control mice eliminated all viable bacteria and became resistant to secondary infection. However, Listeria-infected CB-17 scid mice did show, in parallel with the CB-17 controls, an unexpected and striking increase of Ia-positive macrophages. These data indicate that induction of Ia expression in macrophages can occur via a mechanism that is independent of mature T cells. PMID- 3086457 TI - The extent of oxidative mitogenesis does not correlate with the degree of aldehyde formation of the T lymphocyte membrane. AB - Chemical oxidation of T lymphocytes with periodate or the combined action of the enzymes neuraminidase and galactose oxidase (NAGO) results in T cell activation. The latter process includes the production of interleukin 2 (IL 2) and the induction of IL 2 receptors. Because membrane-bound aldehydes act in the transmission of the oxidative mitogenic signal, we designed a comparative study in human thymocytes and peripheral blood leukocytes in order to determine a possible correlation between the degree of the membrane aldehydes generated chemically or enzymatically and the extent of the resulting activation. The differences between periodate- and NAGO-induced aldehydes were demonstrated by flow cytometry of cells stained with a novel fluoresceinated hydrazide and by an electrophoretic procedure performed with biocytin hydrazide and 125I streptavidin. In both cellular systems, periodate oxidation resulted in stronger formation of aldehydes than NAGO oxidation. However, the IL 2 receptor induced by NAGO formation and the resultant activation were significantly higher than those induced by periodate. The degree of aldehyde formation on peripheral blood leukocytes was also considerably higher than that of thymocytes, yet similar patterns of [3H]thymidine uptake were observed in the mitogenic assays of both cellular systems. The data indicate that no correlation exists between the extent of aldehyde formation and the degree of oxidative mitogenesis. It is thus suggested that relatively few (or maybe only one) membrane-bound aldehyde containing molecules act in the transmission of the oxidative mitogenic signal. PMID- 3086458 TI - T cell-induced expression of membrane IgG by 70Z/3 B cells. AB - To study T cell regulation of B cell isotype differentiation, we determined the capacity of clonal T cell populations (hybridomas derived by fusing BW5147 with Con A-activated Peyer's patch (PP) and spleen T cells) to induce "downstream" isotype expression by the pre-B cell lymphoma 70Z/3. In initial studies, we found that 70Z/3 B cells cultured in the presence of LPS (1 microgram/ml) expressed membrane IgM (mIgM) but not membrane IgG (mIgG). In contrast, 70Z/3 B cells cultured with HAJ-3 T cells, a PP-derived T cell hybridoma (as well as other similarly derived PP and spleen hybridomas), or with HAJ-3 T cells plus LPS do express mIgG. Such expression occurred in spite of mitomycin C-induced blockage of cell proliferation, and is observed in 70Z/3 B cell subclones cultured with HAJ-3 T cells. For these reasons, it is not due to selective expansion of a small pre-switched mIgG-bearing 70Z/3 B cell subpopulation. In other studies it was shown that 70Z/3 B cells expressing mIgG after induction by HAJ-3 T cells continue to express mIgM and do not secrete IgG. Finally, exposure of 70Z/3 B cells to the macrophage factor IL 1 and the T cell factors IL 2, BSF-pl, and BCGF II present in EL-4 cell supernatants did not result in mIgG expression. On the basis of these studies, we conclude that a clonal B cell population expressing mIgM can be induced by T cells to co-express mIgG. Because the B cells do not express mIgG unless exposed to T cells, this represents a T cell-induced isotype switch. PMID- 3086460 TI - M4HS2, a new human T-cell line for the efficient generation of human T-cell hybrids. AB - We have developed and characterised a variant of the human T-cell tumour, MOLT 4F, which is resistant to both 8-azaguanine and 6-thioguanine. This new cell line, M4HS2, is suitable for the efficient production of lymphokine-secreting human T-cell hybrids and is available for distribution. PMID- 3086459 TI - B lymphocyte-associated antigens on terminal deoxynucleotidyl transferase positive cells and pre-B cells in bone marrow of the rat. AB - To investigate early stages of B lymphocytopoiesis in rat bone marrow (BM) before the expression of surface IgM (s mu), the populations of cytoplasmic mu-chain positive (c mu+) pre-B cells and terminal deoxynucleotidyl transferase-positive (TdT+) cells were studied by double immunofluorescence microscopy. B lymphocytes that were s mu+ constituted 5%, c mu+s mu- pre-B cells 23%, and TdT+ cells 4% of nucleated cells in the BM of juvenile rats. TdT+ and pre-B cells ranged between 7 and 17 microns in diameter. TdT+ cells were slightly larger, with a modal diameter of 10.5 microns against 9 microns for pre-B cells. mu-Chains were absent from nearly all TdT+ cells. Their surface antigenic phenotype was studied by using a panel of mouse monoclonal antibodies (MAb) to rat B lymphocyte-associated antigens (Ig, Ia, and others) and T lymphocyte-associated antigens. Both pre-B cells and TdT+ lacked surface Ig and Ia but carried most of the other B lymphocyte-associated antigens analyzed. TdT+ and pre-B cells lacked those antigens found only on the T lineage. By using MAb HIS24 (detecting a non-Ig/Ia B lymphocyte-associated antigen) and fluorescence-activated cell sorting, TdT+ and pre-B cells were highly enriched. The results show that most TdT+ cells in rat BM are mu- but demonstrate strong similarity with pre-B cells in surface antigenic phenotype. Therefore, as suggested for man, a major proportion of rat BM TdT+ cells may be B lineage-cells before mu heavy chain gene expression. PMID- 3086461 TI - Target ricin by coupling to an anti-macrophage monoclonal antibody. AB - By altering the receptor binding specificity of the highly potent natural toxin ricin, a macrophage specific immunotoxin was developed. Ricin ordinarily does not demonstrate cell type specificity and is capable of binding and entering cells through galactose containing receptors resulting in rapid cell death. A murine anti-rat peritoneal macrophage IgGl monoclonal antibody, B-6, was developed to serve as a target specific carrier for ricin. By covalently binding monoclonal antibody B-6 and reversibly binding lactose to ricin, a new biologically active hybrid toxin possessing macrophage specificity was developed. When P3X63-Ag8.653 myeloma cells, which served as an nonspecific target cell type, and macrophages were treated with the ricin conjugate over a broad range of concentrations and various time periods, the conjugate demonstrated substantially greater toxicity toward macrophages than myeloma cells even though both cell types responded similarly to treatments with unconjugated ricin. It was also observed that ricin was considerably more toxic to macrophages when conjugated to monoclonal antibody B-6 than unconjugated ricin. Through ricin-antibody conjugation a high degree of specificity and toxicity can be attained potentially suitable for anti-tumor reagents and immuno-modulators. PMID- 3086462 TI - Increased biosynthesis of lipoxygenase products by UVB-irradiated guinea pig epidermis: evidence of a cyclooxygenase inhibitor. AB - The present studies demonstrate that incubation of arachidonic acid (AA) with a 20,000 g homogenate (containing both microsomal and cytoplasmic fractions) from UVB-irradiated guinea pig epidermis (24-72 h) resulted in decreased transformation of the [14C]AA into the cyclooxygenase products (PGD2, PGE2, and PGF2 alpha) while the incorporation of 14C into lipoxygenase products (15-HETE and 12-HETE) increased. An investigation into the selective inhibition of the cyclooxygenase pathway revealed that the in vitro transformation of [14C]AA into [14C]-cyclooxygenase products by the 100,000 g particulate fraction prepared from normal unirradiated guinea pig epidermis was inhibited by the 100,000 g cytoplasmic extract prepared from a 24-h postirradiated guinea pig epidermis. These latter data imply that an endogenous inhibitor of the cyclooxygenase pathway is generated and released into the cytoplasm during UVB irradiation and it is likely that this selective inhibition of the cyclooxygenase pathway may contribute at least in part to the increased lipoxygenase products in the 24-h postirradiated skin specimens and possibly the recognized prolonged UVB-induced inflammatory process. PMID- 3086463 TI - Influence of Salmonella and other gram-negative bacteria on the survival of mice infected with Schistosoma japonicum. PMID- 3086464 TI - A CO2-enhanced hemolytic activity of Staphylococcus aureus associated with toxic shock syndrome: inhibition by agar. PMID- 3086465 TI - Bactericidal effects of polyunsaturated fatty acids. AB - Bactericidal effects of polyunsaturated fatty acids were investigated by using an in vitro killing assay. All gram-positive species tested were extremely susceptible to 10(-5) M arachidonic acid as were Neisseria, Branhamella, and Haemophilus spp. Pseudomonas aeruginosa and and members of the Enterobacteriaceae were resistant. The toxicity of polyunsaturated fatty acids for Staphylococcus aureus was dependent upon time, concentration, and fatty acid unsaturation. Arachidonic acid underwent peroxidation when incubated with S. aureus, but arachidonic acid peroxidation products had low bactericidal activity. Catalase protected S. aureus, whereas superoxide dismutase was ineffective. Scavengers of hydroxyl radicals or singlet oxygen or removal of halide ions had little effect on arachidonic acid-induced killing of bacteria, whereas transition metal chelators and some thiols were highly protective. S. aureus grown in iron supplemented broth had increased iron content and arachidonic acid susceptibility. Ascorbate also potentiated arachidonic acid-induced killing of S. aureus. These observations indicate that bactericidal effects of polyunsaturated fatty acids are mediated by a peroxidative process involving H2O2 and bacterial iron. PMID- 3086466 TI - [Surgical treatment of advanced valvular heart disease in patients with cardiac cachexia]. PMID- 3086468 TI - Lack of Mycobacterium leprae-specific uptake in Schwann cells. AB - Among mycobacteria, Mycobacterium leprae have a unique property to infect peripheral nerves, which is the cause of a variety of debilities seen in leprosy. The possibility of selective uptake of M. leprae by Schwann cells was studied using a rat Schwannoma cell line 33B and rat sciatic nerve-derived Schwann cells. M. leprae were phagocytosed by 33B cells but so also were seven other mycobacteria ("Mycobacterium w," BCG, M. tuberculosis H37Rv, M. nonchromogenicum, M. vaccae, ICRC bacillus, and M. smegmatis) which do not involve peripheral nerves. All three mycobacteria tested (M. leprae, M. tuberculosis and "Mycobacterium w") were phagocytosed by sciatic nerve-derived Schwann cells. Both Schwannoma and Schwann cells phagocytosed even inert latex particles. These results fail to demonstrate any M. leprae-specific uptake system in Schwann cells. PMID- 3086467 TI - Immunity to leprosy. III. The in vitro induction of B lymphocyte proliferation by mycobacteria. AB - The development of murine proliferative response assays has been initiated to begin to evaluate T-lymphocyte responses to the antigens of Mycobacterium leprae. In this study, M. leprae and 13 related strains of mycobacteria have been tested for stimulatory effects in proliferation assays using murine spleen, thymus or lymph node cultures. A number of mycobacteria were found to directly stimulate the proliferation of spleen and lymph node cells of all mouse strains tested including C3H/HeJ mice. Thymocyte cultures showed no response. The mitogenic effects of mycobacteria in spleen cultures were not dependent upon the presence of T cells or adherent cells, and resulted in the production of antibody-forming cells. Thus, these bacteria acted as polyclonal B-cell mitogens and could be readily distinguished from the lipopolysaccharide of Gram-negative bacteria by their mitogenic activity on C3H/HeJ spleen cells. The species of mycobacteria which exhibit direct mitogenic effects in spleen and lymph node cultures are a particular problem when specific immune responses to the antigens of these bacteria are compared. Such comparisons are necessary if in vitro assays are to be used to determine the nature of crossreactive antigens between M. leprae and other mycobacteria. PMID- 3086469 TI - [Polarized light microscopy findings of the dental hard tissues irradiated with a CO2 laser]. PMID- 3086470 TI - Disseminated intravascular coagulation following Echis carinatus venom in dogs: effects of a synthetic thrombin inhibitor. AB - Disseminated intravascular coagulation (DIC) was produced by an infusion of a prothrombin activator (Echis carinatus venom; 30 minutes; 0.5 NIH thrombin equivalent U/kg) in mongrel dogs (Echis group, n = 7). Fibrinogen declined to below measurable levels (less than 25 mg/dl), and fibrin-fibrinogen degradation products appeared (53 +/- 8 micrograms/ml) at end venom infusion in the Echis group. These alterations were not seen when an irreversible thrombin inhibitor, D phenylalanyl-L-prolyl-L-arginine-L-chloromethyl ketone (PPACK) (57 nmol/kg/min for 120 minutes), was given alone (PPACK group, n = 5) or in association with venom (Echis + PPACK group, n = 5). Factor II activity (1% +/- 1%) in the Echis and Echis + PPACK groups was significantly below the PPACK (55% +/- 9%) and the control (79% +/- 2%) levels at 120 minutes. In contrast, factor VIII coagulant (factor VIII:C) activity in the Echis group (1% +/- 1%) remained significantly below that in the Echis + PPACK (68% +/- 8%), PPACK (78% +/- 10%), and control (91% +/- 9%) groups at this interval. No change in factors X (91% +/- 7% to 81% +/- 7%, P not significant) and VII (64% +/- 10% to 48% +/- 11%, P not significant) activities were observed. Hemolysis was observed only in the Echis group, whereas thrombocytopenia and leukopenia were noted in both the Echis and the Echis + PPACK groups. These data show that large amounts of E. carinatus venom produce rapid DIC in vivo, because of the activation of prothrombin. In contrast, the decline in factor VIII:C activity appeared to be the result of the liberated thrombin. PPACK antagonized all of the venom-released thrombin without any major deleterious clotting abnormalities. This inhibitor appears to prevent thrombin-mediated DIC in vivo. In contrast, heparin was found to be an unreliable antagonist of the venom-released thrombin in vitro. PPACK also inhibited the marked hemolysis usually observed after venom. In addition, we found that the esterolytic (N-benzoyl-L-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide HCL) activity of E. carinatus venom degrades fibrinogen in vitro. PMID- 3086471 TI - Hemodialysis hemodynamics in an animal model: effect of using an acetate-buffered dialysate. AB - Acetate-buffered dialysis (procedure A) was performed in conscious, nonuremic, splenectomized dogs. In some animals, dialysis was repeated after sympathectomy with 6-hydroxydopamine. During procedure A, hemodynamic changes were most pronounced 1 minute after starting dialysate flow (acute phase), and included a marked rise in cardiac output, pulse rate, and mean pulmonary artery pressure, but no change in mean arterial pressure (MAP) in intact animals. However, a precipitous fall in MAP was noted in sympathectomized dogs. Plasma acetate levels at this time averaged 2.0 +/- 0.5 mmol/L. Six to 30 minutes into procedure A, hypotension could be demonstrated in the intact, but not in the sympathectomized animals, at which time plasma acetate levels averaged 2.2 to 2.7 mmol/L. At 60 to 90 minutes into dialysis, when plasma acetate levels averaged 3.0 +/- 0.8 mmol/L, hypotension with procedure A was no longer significantly greater than with bicarbonate-buffered dialysis (procedure B). Plasma acetate levels at 30 to 90 minutes correlated with the change in cardiac output (r = 0.86, P less than 0.05) and total peripheral resistance (r = -0.76, P less than 0.05), but not with the decrease in MAP (r = -0.43, P not significant). Substantial hemodynamic changes were not seen when bicarbonate-buffered dialysis was used. Our results suggest that acute hypotension during procedure A in the dog model is prevented by an intact sympathetic nervous system. Hypotension occurring later during procedure A is difficult to demonstrate and does not appear to be accentuated after chemical sympathectomy. During procedure A the increase in cardiac output correlates with plasma acetate level. PMID- 3086472 TI - Hemolytic activity of leukemic sera: the role of complement and sucrose. AB - In sera of patients with acute myeloblastic leukemia (AML), hemolytic activity can be demonstrated in vitro in the presence of sucrose. To investigate the nature and the mode of action of this hemolytic activity, serum samples from 24 patients with AML were studied by incubation of normal human erythrocytes together with patient serum in the presence of sucrose at low ionic strength (inverse sucrose hemolysis test, ISHT). Fifty-five percent of the serum samples collected during the active stage of the disease gave a hemolysis rate of greater than 4%, whereas in remission only 15% of the samples lysed erythrocytes. Substitution of raffinose, lactose, or polyethylene glycol 400 for sucrose resulted in an almost complete failure of hemolysis under standard conditions, indicating a minor role of the low ionic strength in the ISHT. Heat inactivation, preincubation with inulin, and addition of EDTA, Mg2+-EGTA, or heparin completely abolished hemolytic activities of AML sera when the incubation was carried out for 30 minutes (standard conditions of the ISHT). A prolongation of the incubation time resulted in delayed hemolysis only with the Mg2+-EGTA-treated AML sera. The kinetics of this hemolysis by Mg2+-EGTA-treated AML sera were similar to those of normal human serum in the presence or absence of Mg2+-EGTA. Hemolysis was also obtained by performing the ISHT with normal sera and erythrocytes preincubated with AML sera. These observations suggest a mediation of membrane modification of normal human erythrocytes by AML sera in the presence of sucrose, resulting in an activation of the classical pathway of complement. PMID- 3086473 TI - Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo. AB - The inhibition of one-chain and two-chain molecular forms of human tissue-type plasminogen activator (t-PA) by the fast-acting inhibitor of plasminogen activator (PA-inhibitor) present in plasma was studied in vitro and in vivo in rabbits. In vitro, both one-chain and two-chain forms of t-PA were neutralized very rapidly in rabbit plasma with high levels of PA-inhibitor. The rate constant of the interaction between two-chain t-PA and PA-inhibitor was estimated to be 3.10(7) L/mol/sec. The presence of CNBr-digested fibrinogen, which mimics the effect of fibrin on the activation of plasminogen by t-PA, did not influence the rate constant. Moreover, PA-inhibitor-rich plasma inhibited in a very similar way in vitro thrombolysis by one-chain or two-chain t-PA incorporated into the clot. Injection of one-chain or two-chain t-PA into rabbits with increased levels of PA inhibitor, induced by endotoxin, resulted in very rapid inhibition of t-PA activity. Within 30 seconds after injection, no residual free t-PA could be demonstrated. Gel filtration analysis showed that the disappearance of t-PA activity was associated with the generation of t-PA-PA-inhibitor complex with an apparent Mr of 100,000. This enzyme-inhibitor complex, like free t-PA, was cleared from the circulation with a half-life of approximately 2 minutes, mainly via the liver. It is concluded that PA-inhibitor neutralizes one-chain and two chain molecular forms of t-PA in plasma at very similar rates, both in vitro and in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086474 TI - Effect of moderate prolonged ethanol ingestion on intestinal disaccharidase activity and histology. AB - A previous study has shown that long-term feeding of ethanol in high doses (36% of total calories) causes marked changes in intestinal mucosal disaccharidase activity as well as blunting of the intestinal villi. To determine whether similar damage occurs in response to a more moderate ethanol exposure, we pair fed rats a liquid diet that provided 15.5% of total calories from ethanol for 5 weeks. In the proximal segment of the intestine, we found that ethanol did not affect the total activities of maltase (8.0 +/- 2.4 U vs. control value of 6.7 +/ 1.8 U), sucrase (1.5 +/- 0.5 U vs. control of 1.2 +/- 0.3 U), or lactase (125 +/ 42 mU vs. control of 107 +/- 36 mU). Similarly, we found no differences from control values for the three disaccharidases in the middle or distal small bowel. The mucosal protein content of the experimental animals did not differ from values found in the control animals. In addition, no change in intestinal villus height or crypt depth was detected. The zinc content of hair and serum was not affected by the ethanol feeding. We conclude that prolonged ingestion of a moderate dose of ethanol does not damage the small intestinal disaccharidase enzymes, mucosal protein content, or intestinal architecture. PMID- 3086475 TI - Effect of long-term infusion of an LH-releasing hormone agonist on testicular function in bulls. AB - Continuous administration of LH-releasing hormone (LHRH) agonists is an effective method of suppressing testosterone secretion in the male. The effect of the LH releasing hormone (LHRH) agonist, buserelin, administered to bulls by constant infusion from osmotic minipumps was studied. In one experiment with four treated and one control bull, 109 micrograms buserelin/day were administered for 22 days. Immediately after implantation, serum testosterone concentrations rose from below 35 nmol/l to 35-105 nmol/l, and all four buserelin-infused bulls showed increased testosterone secretion during the treatment period. After removal of the minipumps, testosterone concentrations decreased to pretreatment levels. In a second experiment bulls were infused for 42 days (four treated and one control), and identical results were obtained. Testosterone secretion was stimulated (52-87 nmol/l serum) during the entire treatment period. These results demonstrate that conditions for stimulation of the pituitary-testicular axis may vary between species. Infusion of low doses of LHRH-agonists in bulls has an extended stimulatory effect without immediate desensitization of gonadotrophin release. PMID- 3086476 TI - Varying the patterns and concentrations of gonadotrophin-releasing hormone stimulation does not alter the ratio of LH and FSH released from perifused sheep pituitary cells. AB - Our aim was to determine whether release of LH and FSH can be controlled differentially by the characteristics of applied signals of stimulatory gonadotrophin-releasing hormone (GnRH) alone, free of the effects of steroid feedback or other influences from the whole animal. The outputs of both gonadotrophins were significantly correlated (r approximately 0.90; P less than 0.0005) when samples of freshly dispersed sheep pituitary cells were perifused in columns for 7 h with medium containing a range of concentrations of GnRH in various patterns of pulses. Hormone released in response to the second, third and fourth pulses from every column was analysed in detail. Dose-response relationships for both LH and FSH were very similar when cells were stimulated with 5-8500 pmol GnRH/l in 5-min pulses every hour. When GnRH was delivered in pulses at a maximally stimulating level, the outputs of both hormones increased similarly with increasing inter-pulse intervals. Efficiency of stimulation (release of gonadotrophin/unit stimulatory GnRH) decreased (was desensitized) with increasing pulse duration in the same way for both hormones. Thus, varying the dose, interval and duration of GnRH pulses did not alter the proportions of LH and FSH released in the short-term from freshly dissociated cells. However, the same cell preparations released more LH relative to FSH when treated with maximally stimulating levels of GnRH for 3 h in the presence of 10% serum from a sheep in the follicular phase of its ovulatory cycle compared with charcoal treated serum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086477 TI - An immunocytochemical and electron microscopic study of the hyt mouse anterior pituitary gland. AB - The hyt mutant mouse used in this study has a hypoplastic thyroid gland and is characterized by retarded somatic growth, very low to undetectable levels of plasma thyroxine (T4), and increased levels of plasma thyroid-stimulating hormone (TSH). This congenital hypothyroid mouse is therefore an ideal model for studying the effects of thyroid hypofunction on the adenohypophysis. The anterior pituitary of the hyt mouse appeared less granular than that of the normal control when viewed by light microscopy, owing to a decrease in the population of somatotrophs. Many cells, in various stages of transformation into 'thyroidectomy cells', were recognized by the appearance of the characteristic granules and dilated rough endoplasmic reticulum. In some cases, the enlarged rough endoplasmic reticulum also contained spherical electron-dense secretory granules. In addition there were many cells undergoing mitosis and these were identified as thyrotrophs by their characteristic granules. Administration of T4 during the first 40 days of life prevented the abnormal changes in the hyt anterior pituitary. A reduction in immunoreactive thyrotrophin-releasing hormone (TRH) levels was seen in the median eminence of the hyt mouse. Treatment with T4 restored this to normal, suggesting that the reduced TRH content of the hypothalamus of the mutant mouse may be due to T4 deprivation. PMID- 3086478 TI - Thyrotrophin-releasing hormone does not accumulate glycosylated thyrotrophin, but changes heterogeneous forms of thyrotrophin within the rat anterior pituitary gland. AB - We have investigated the effect of TRH on the accumulation of glycosylated TSH in the rat anterior pituitary gland. Hemipituitaries from adult male rats were incubated in medium containing [3H]glucosamine in the presence of TRH. [3H]Glucosamine-labelled TSH in media and pituitaries was measured by immunoprecipitation and characterized by isoelectric focusing after affinity chromatography. Incorporation of [3H]glucosamine into immunoprecipitable TSH in the media and pituitaries increased progressively with the period of incubation. Although the release of [3H]glucosamine-labelled and unlabelled TSH into media was stimulated by the addition of TRH in a time- and dose-dependent manner, TRH administration did not alter the amounts of labelled or unlabelled TSH in the anterior pituitary lobes. The anterior pituitaries were found, by isoelectric focusing analysis, to be composed of four major component peaks of [3H]glucosamine-labelled TSH. Administration of TRH caused profound changes in the radioactivity of these components and evoked new radioactive peaks, resulting in the appearance of six components in total. The present data provide evidence that TRH significantly changes the heterogeneity of glycosylated TSH in the anterior pituitary without altering the amount of the glycosylated form. PMID- 3086479 TI - Age-related changes in the concentrations of serum gonadotrophins and cholesterol in the female rabbit. AB - Peripheral serum concentrations of LH, FSH and prolactin were determined by radioimmunoassay on different days after birth in the female rabbit. Serum cholesterol concentrations were also analysed by a colorimetric method. Concentrations of serum LH and FSH showed two distinct peaks occurring on day 9 (LH, 4.05 +/- 0.76 (mean +/- S.E.M.) micrograms/l; FSH, 3.62 +/- 0.67 microgram/l) and either day 35 (LH, 5.90 +/- 1.20 micrograms/l) or day 40 (FSH, 9.01 +/- 1.43 micrograms/l). Concentrations of LH and FSH were in the adult range (LH, less than 1 microgram/l; FSH, less than 0.6 micrograms/l) by day 100. Serum prolactin showed a progressive increase from day 1 (1.04 +/- 0.07 microgram/l) to day 100 (17.30 +/- 2.50 micrograms/l) with a peak on day 40. Total serum cholesterol in another series of rabbits was high from days 1 to 22 (7.53 +/- 0.64 mmol/l) and then decreased to 1.94-3.36 mmol/l by day 106. These data indicate that the two major developmental peaks in gonadotrophins may be related to ovarian function. PMID- 3086480 TI - Interleukin 2 receptor expression in unstimulated murine splenic T cells. Localization to L3T4+ cells and regulation by non-H-2-linked genes. AB - The present study reports the surprising observation that IL-2-R+ cells can be detected in fresh, unstimulated, murine spleen T cells from unimmunized mice by flow cytometry using the monoclonal anti-receptor antibody 7D4. Also, unexpectedly, these cells were found exclusively in the L3T4+Lyt-2- population by two-color fluorescence, in contrast to receptor+ cells after stimulation, in which both L3T4+Lyt-2- and Lyt-2+L3T4- cells were found. The fraction of splenic T cells bearing IL-2-R reproducibly varies twofold under non-H-2-linked genetic control, with high expression in DBA/2 and BALB/c (approximately 6-7%) and low expression in B10.D2 and C57BL/6 (3%). This correlates quantitatively with a greater responsiveness of the DBA/2 and BALB/c splenic T cells to high doses of IL-2, compared with B10.D2 T cells; twice as many B10.D2 T cells as DBA/2 T cells were required to get the same response. Studies with 23 B X D RI strains revealed that the level of IL-2-R+ cells in unstimulated spleen cells was regulated by multiple genes, very likely including at least one gene on chromosome 7, near the HBB locus. The mapping makes novel use of nonparametric (Smirnov) statistics, which we suggest may be of general usefulness in similar analyses of RI strains. PMID- 3086481 TI - Purification to homogeneity of B cell stimulating factor. A molecule that stimulates proliferation of multiple lymphokine-dependent cell lines. AB - Murine B cell stimulating factor 1 (BSF-1) was purified to homogeneity from supernatants of a stimulated thymoma cell line. A protein of 18.4 kD with a unique N-terminal amino acid sequence was identified. BSF-1 had a sp act of at least 3.28 X 10(8) U/mg. In addition to its B cell-stimulatory activity, BSF-1 also stimulated the proliferation of several IL-2- and IL-3-dependent cell lines. We conclude that BSF-1 is both a growth factor and a differentiation factor. Finally, these results also suggest additional biologic properties of BSF-1 on lineages besides B lymphocytes. PMID- 3086482 TI - Involvement of the T cell antigen receptor and of Lyt-2 in the cytotoxic function of aged killer (AK) T cells. AB - Aged killer (AK) T cells are antigen-independent, IL-2-requiring variants of antigen-dependent CTL clones that have lost their original antigen specificity and have acquired, instead, specific cytotoxicity for P815 target cells. In this report we study whether AK cells use a similar or a different target cell recognition system than that of bona fide CTL. To this end, we selected from a cloned AK line variants that are partially or completely deficient in specific target recognition and/or in cytotoxic function, and analyzed these variants for expression of the T cell antigen receptor and of Lyt-2. Variants were selected from the prototype AK line (Cl 96) with specific, as well as lectin-facilitated, cytotoxicity for P815 tumor cells. Variants could be grouped into four types with increasing degrees of functional deficiency, which correlated with loss of T cell receptor and/or loss of Lyt-2. In short, loss of Lyt-2 was reflected in loss of specific target recognition, and loss of the T cell antigen receptor was reflected in loss of all cytotoxic activity. We conclude from these results that both Lyt-2 and the T cell antigen receptor are required for specific target cell recognition and the T cell antigen receptor is, in addition, required for cytotoxic function. Moreover, since AK cells express a somatically acquired specificity that differs from that of their clonal precursors, it appears that cytotoxic T cells may change their antigen receptor from one specificity to another during tissue culture. PMID- 3086484 TI - A statewide university hospital-based family medicine referral service. AB - A statewide university hospital-based family medicine referral service was established at the University of Oklahoma in July 1983. During the first six months of operation, 14 percent of all patients admitted to the family medicine inpatient service were referred by outside physicians. Referral patients had more diagnoses coded per admission (2.25) than continuity patients (1.56) (P less than .05). In referral patients, 23.3 percent of diagnoses fell into the 52 most common diagnostic cluster described by Rosenblatt et al compared with 50.9 percent in continuity patients (P less than .0005). Specialty consultations, invasive diagnostic procedures, surgical procedures, and average length of hospital stay were compared in the subgroup of patients with medical, pediatric, surgical, and gynecological principal diagnoses. Referred patients averaged 0.974 consultations per admission compared with 0.578 in continuity patients (P less than .01). An average of 1.237 invasive diagnostic procedures per admission were performed in referral patients compared with 0.626 in continuity patients (P less than .0005). Referral patients averaged 0.145 surgical procedures per admission compared with 0.123 in continuity patients (not significant). The average length of stay for both continuity and referral patients was 9.68 days per admission. A survey of the referring physicians indicated that both the physicians and the patients whom they referred were generally satisfied with the care provided by the service. PMID- 3086483 TI - Interleukin 1 induces endothelial cell synthesis of plasminogen activator inhibitor. AB - Human endothelial cells activated with IL-1 express a surface membrane-oriented procoagulant generating system characterized by increased tissue factor synthesis and decreased thrombomodulin activity. We now report that IL-1 also stimulates endothelial cell synthesis of plasminogen activator inhibitor. This array of IL-1 induced activities shifts the balance at the endothelial cell surface to a prothrombotic influence and may reflect an early response of the blood vessel wall to injury. PMID- 3086485 TI - Relationship between calcium binding sites and membrane fusion during the acrosome reaction induced by ionophore in ram spermatozoa. AB - Ram spermatozoa treated with the ionophore A23187, to induce the acrosome reaction, were fixed in pyroantimonate-osmium in order to demonstrate calcium at an ultrastructural level. Prior to vesiculation, granules of precipitate occurred at points of contact between plasma and outer acrosomal membranes, suggesting a discrete role for calcium during membrane fusion. The earliest stages of vesiculation always occurred in the region just anterior to the equatorial segment and it was this same site where a marked concentration of precipitate, indicating calcium binding sites, could be demonstrated. PMID- 3086486 TI - Cell surface carbohydrate involvement in controlling the adhesion and morphology of neural crest cells and melanophores of Xenopus laevis. AB - Pieces of dorsal neural tube (stages 22-23) or late neural crest tissue (stages 24-26) of Xenopus laevis were cultured. Migratory cells moved out of explants to form an outgrowth of multipolar melanophores on the substratum. Treatment with beta-galactosidase (0.1-0.4 U/ml) to remove cell surface galactose was correlated with detachment of melanophores. In the presence of lower concentrations of this enzyme the shapes of these cells were converted to arborized, spidery morphologies and cell movement was inhibited. Unpigmented cells were affected more slowly. Neuraminidase treatment, to remove cell surface sialic acid and expose more galactose, only affected melanophores. These became increasingly spread on the substratum and cell overlap was observed. These results suggest that the relative amounts of galactose and sialic acid at the cell surface become increasingly important in controlling cell adhesion as X. laevis neural crest cells migrate and differentiate into melanophores. PMID- 3086488 TI - A new method for softening mummified fingers. AB - Proposed methods for softening mummified fingers have been either unsuccessful in adequately softening the fingers or have been highly destructive. A simple technique based on an entirely new concept utilizing disodium ethylenediamine tetraacetic acid in a detergent solution adjusted to a pH of 7.5 has been successfully used to obtain satisfactory to good fingerprints over the past ten years in every case attempted. PMID- 3086487 TI - Spectral differentiation and gas chromatographic/mass spectrometric analysis of the lacrimators 2-chloroacetophenone and o-chlorobenzylidene malononitrile. AB - 2-Chloroacetophenone (CN) and o-chlorobenzylidene malononitrile (CS) are the most common chemical agents used as lacrimators in the United States. There is a lack of complete spectral data on these compounds in the literature. Spectral data (ultraviolet, fluorescence, proton nuclear magnetic resonance, and infrared) and a gas-liquid chromatographic/mass spectrometric method are presented that differentiate and identify CN and CS. These methods and data were used to identify a forensic science specimen from an accidental intoxication. PMID- 3086489 TI - Pharmaceutical error resulting in fatal diabetic ketoacidosis. AB - A 41-year-old male with a 25-year history of diabetes mellitus requiring 25 to 30 units of neutral protamine hagedorn (NPH) insulin daily was found dead at home. Recent history revealed that he was well until the last four days of life when he had the onset of nausea, vomiting, and anorexia coinciding with procurement of a new bottle of insulin from his pharmacist. Pertinent autopsy findings included coronary and aortic atherosclerosis, a peptic ulcer, and diabetic glomerulopathy. Chemical analysis of the vitreous humor, including glucose (813 mg/dL) and acetone (40 mg/dL), revealed that he died of diabetic ketoacidosis. Further investigation revealed that the pharmacist had accidentally substituted regular insulin, with a duration of action of up to 6 h as opposed to 24 to 28 h, for NPH. Cultures of blood and of the regular insulin yielded no growth. Analysis of this case emphasizes the importance of obtaining a careful medical and medication history and the usefulness of vitreous electrolytes when investigating a sudden death in a diabetic. PMID- 3086490 TI - Heterogeneities of two components of C2 toxin produced by Clostridium botulinum types C and D. AB - Botulinum C2 toxin (C2T) is composed of two dissimilar protein components, designated components I and II, which are linked with neither covalent nor noncovalent bonds. The heterogeneity of these two components of C2T produced by Clostridium botulinum type C and D strains was examined. Of 21 strains examined, 19 strains produced the two components, while the others produced neither component I nor component II. The 19 producers of C2T could be divided into three groups based on the differences in antigenicity, molecular weight and biological activity of components I and II. The results provide evidence of heterogeneity in the molecular structure of the two components of C2T, which is possibly a cause of the differences in the biological activity of the toxin observed in different strains. PMID- 3086491 TI - Ionophores and cytochalasins modulate branching in Achlya bisexualis. AB - Hyphae of Achlya bisexualis growing on a medium deficient in amino acids elongated but produced relatively few branches. Branching was enhanced by three classes of compound: cytochalasins A and E, the calcium ionophores A23187 and ionomycin and proton ionophores such as tetrachlorosalicylanilide (TCS), carbonylcyanide m-chlorophenylhydrazone (CCCP), and carbonylcyanide p trifluoromethoxyphenylhydrazone (FCCP). We suggest that the effects of cytochalasins reflect the disruption of a microfilament-based system for vesicle transport. Enhancement of branching by ionophores implicates cytoplasmic ions in the control of branch initiation. There may be links between these phenomena and the earlier discovery that a new point of proton entry precedes the emergence of a branch and predicts its locus. PMID- 3086492 TI - The permeability parameter of the outer membrane of Pseudomonas aeruginosa varies with the concentration of a test substrate, cephalosporin C. AB - The permeability parameter (C) for the movement of cephalosporin C across the outer membrane of Pseudomonas aeruginosa was measured using the widely accepted method of Zimmermann & Rosselet. In one experiment, the value of C varied continuously from 4.2 to 10.8 cm3 min-1 (mg dry wt cells)-1 over a range of concentrations of the test substrate, cephalosporin C, from 50 to 5 microM. Dependence of C on the concentration of test substrate was still observed when the effect of a possible electric potential difference across the outer membrane was corrected for. In quantitative studies of beta-lactam permeation the dependence of C on the concentration of beta-lactam should be taken into account. PMID- 3086493 TI - Regeneration of protoplasts of Bacillus subtilis 168 and closely related strains. AB - Regeneration of protoplasts to bacilli was attempted in several strains of Bacillus closely related to Bacillus subtilis 168. On DM3 and similar media using succinate as osmotic support, only B. subtilis 168 and Bacillus natto ATCC 15245 were able to regenerate. Media containing mannitol as osmotic support, and agar as gelling agent gave rise to L-form colonies with Bacillus licheniformis NCTC 6346. Many of the L-form colonies were able to regenerate to the bacillary form when plated on the mannitol medium solidified with gelatin. All of the Bacillus species tested were able to regenerate on the latter medium at rates sufficient to allow protoplast transformation and fusion experiments. PMID- 3086494 TI - Cloning, expression and location of the Streptococcus lactis gene for phospho beta-D-galactosidase. AB - Genes for lactose catabolism and proteinase production in Streptococcus lactis 712 are encoded by a 56.5 kb metabolic plasmid, pLP712. A lactose mini-plasmid of only 23.7 kb, pMG820, was constructed by introducing two deletions into pLP712, and was cloned as two segments of DNA into the Escherichia coli vector pAT153 using restriction endonuclease PstI. The lactose genetic region of pLP712, which has been defined by deletion and restriction mapping, was cut into two parts by this process. When the smaller 10.8 kb segment of pMG820 DNA was present, the key lactic streptococcal lactose splitting enzyme, phospho-beta-D-galactosidase, was expressed in E. coli. The gene for phospho-beta-D-galactosidase was more precisely located by introducing a series of deletions into cloned DNA by in vitro manipulations and then assaying for enzyme activity. The presence of this phospho-beta-D-galactosidase activity was correlated with the production of a 58 kDa 35S-labelled protein both by E. coli minicells and after coupled transcription and translation of cloned DNA. The product of a second gene, a 37 kDa protein ('protein X'), and a possible truncated phospho-beta-D-galactosidase protein of 16 kDa were also detected in minicells. PMID- 3086495 TI - Microcin B17 blocks DNA replication and induces the SOS system in Escherichia coli. AB - Microcin B17 is a novel peptide antibiotic of low Mr (about 4000) produced by Escherichia coli strains carrying plasmid pMccB17. The action of this microcin in sensitive cells is essentially irreversible, follows single-hit kinetics, and leads to an abrupt arrest of DNA replication and, consequently, to the induction of the SOS response. RecA- and RecBC- strains are hypersensitive to microcin B17. Strains producing a non-cleavable SOS repressor (lexAl mutant) are also more sensitive than wild-type, whereas strains carrying a mutation which causes constitutive expression of the SOS response (spr-55) are less sensitive to microcin. Microcin B17 does not induce the SOS response in cells which do not have an active replication fork. The results suggest that the mode of action of this microcin is different from all other well-characterized microcins and colicins, and from other antibiotics which inhibit DNA replication. PMID- 3086496 TI - Resistance of a Bacillus subtilis mutant to a group of temperate bacteriophages. AB - A mutant of Bacillus subtilis 168 was isolated which resists infection by all the group III temperate bacteriophages except SPR, while allowing full infection by phages of the other groups (I, II and IV). The mutation conferring this phenotype, pha-3, shows 52-54% PBS1-mediated cotransduction with the hisAl marker, mapping therefore in the gtaA and gtaB region of the B. subtilis chromosome. Nevertheless, it does not affect the infection by phages sensitive to gta mutations. PMID- 3086497 TI - Physiological characteristics of the Mycobacterium tuberculosis-M. bovis group of organisms with particular reference to heterogeneity within M. bovis. AB - By examining the abilities of mycobacterial strains to remove amino acids from solution, differences were found between Mycobacterium tuberculosis and other closely related taxa. Heterogeneity was observed in most taxa. Strains of M. bovis were examined in greater detail. By using the amino acid typing method in combination with tests routinely used for differentiating mycobacterial species, and SDS-polyacrylamide gel electrophoresis of whole cell soluble proteins, a great degree of heterogeneity was observed in this taxon. PMID- 3086499 TI - Virulence and immunogenicity in experimental animals of Bacillus anthracis strains harbouring or lacking 110 MDa and 60 MDa plasmids. AB - A comparative study was made of the virulence and immunogenicity in mice or guinea pigs of Bacillus anthracis strains harbouring 110 MDa and/or 60 MDa plasmids. Strains cured of the 110 MDa or the 60 MDa plasmid were more than 100 fold less virulent to mice than were the parental strains harbouring these plasmids. Guinea-pigs immunized with plasmid-free derivatives of the non encapsulated vaccine strain 34F2 showed no resistance to challenge with strain 17JB, which harbours both 110 MDa and 60 MDa plasmids, suggesting that the derivative strains had lost their immunizing ability against anthrax. PMID- 3086498 TI - Inhibition of sporulation in Bacillus subtilis by bromodeoxyuridine and the effect on DNA replication. AB - A 5-bromo-2'-deoxyuridine (BUdR)-tolerant derivative of a thymidine (TdR) requiring strain of Bacillus subtilis was used to examine the effect of BUdR, an analogue of TdR, on sporulation. At a TdR:BUdR ratio which had little effect on growth, sporulation was inhibited if cells were exposed to BUdR during the period of DNA synthesis at the onset of the process. Cells recovered from BUdR inhibition of sporulation if the analogue was removed and DNA replication allowed to continue with TdR alone. BUdR prolonged the period of DNA synthesis during sporulation and experiments with chloramphenicol suggested that this was due in part to unscheduled initiation of new rounds of replication. PMID- 3086500 TI - Activity of two strong promoters cloned into Bacillus subtilis. AB - Two DNA fragments, one encoding the Escherichia coli trc promoter and the other encoding a sequence from the early region of Bacillus subtilis phage SPO1, were cloned into the B. subtilis promoter-probe vector pPL603. Both fragments effected strong in vivo promoter activity in vegetative B. subtilis cells. PMID- 3086501 TI - Pathogenicity and persistence of pleural effusion disease virus isolates in rabbits. AB - Nine isolates of pleural effusion disease agent or virus (PEDV) from treponema infected rabbits in various countries were examined for pathogenicity and persistence in rabbits. The isolates showed a wide range of pathogenicity and were categorized into three groups according to the severity of the acute infection. Group 1 comprised isolates causing more than 50% mortality, group 2 isolates causing mortality below 50%, while group 3 comprised isolates causing almost subclinical infections. The range between group 1 and group 3 was similar to that observed with virulent and avirulent progeny of the original PEDV isolate. Infection by each of the nine isolates resulted in a chronic low level viraemia which persisted for up to 2 years or more. Viral progeny of pathogenic isolates obtained in serum after the 2nd month of infection failed to induce clinical disease on rabbit inoculation. The chronic, subclinical infection was associated with a moderate, continued increase in serum IgG, but circulating immune complexes could not be demonstrated. Two years after infection slight histopathological changes were present in lymph nodes, spleen, liver, heart and lung. Evidence of immune complex disease could not be demonstrated. PMID- 3086502 TI - Diabetes: Part V. Detection and prevention of acute hyperglycemia and ketoacidosis. PMID- 3086503 TI - Dementia in idiopathic Parkinson's disease. Variables associated with its occurrence in 203 patients. AB - A series of 203 patients with primary Parkinson's disease treated with L-DOPA, with adequate neurological documentation of mental status at serial intervals during their illness, constitutes the study population. Based on the results of the latest neurological examination, slightly less than one-third (29%) had mental impairment assessed as neurologically significant. Of the eleven clinical variables analysed (Cox regression analysis) for potential influence on the occurrence of an organic mental syndrome, four had a statistically significant effect: (1) the stage of disease at initial neurological examination; (2) the occurrence of acute confusional states; (3) the years of Parkinson's prior to L DOPA; and (4) the total duration of L-DOPA therapy. The pathogenesis of dementia in this subgroup of Parkinson's disease is discussed. PMID- 3086504 TI - Effect of CDP-choline on hypocapnic neurons in culture. AB - Neuronal cultures from chick embryo cerebral hemispheres were protected against a hypocapnic injury by adding to their growth medium 10(-6)M CDP-choline before or after the injury. The protection obtained with CDP-choline was analyzed by a morphometric analysis and showed that pretreatment of neuronal cultures with CDP choline maintained the number of cell aggregates and of primary neuronal processes at control values after hypocapnic shock. Various experiments showed that the intact molecule was responsible for the protective action, since pretreatment with different concentrations of various nucleosides and nucleotides (up to 10(-5) M), choline, and phosphorylcholine was without protective effect. The addition of CDP-choline after the hypocapnic injury resulted in a protection of the cultures as shown by morphological observation. Incubation of neurons with radioactive choline showed that hypocapnia increased the incorporation of the label into phospholipids whereas the presence of CDP-choline reduced it. The de novo synthesis of choline was affected by neither hypocapnia nor CDP-choline treatment. The results indicate that CDP-choline may have the capacity to protect neurons under conditions of basic pH and that cellular proliferation may be stimulated by the compound. PMID- 3086505 TI - Effects of purine nucleotides on the binding of [3H]cyclopentyladenosine to adenosine A-1 receptors in rat brain membranes. AB - Adenine nucleotides displace the binding of the selective adenosine A-1 receptor ligand [3H]cyclopentyladenosine (CPA) to rat brain membranes in a concentration dependent manner, with the rank order of activity being ATP greater than ADP greater than AMP. Binding was also displaced by GTP, ITP, adenylylimidodiphosphate (AppNHp), 2-methylthioATP, and the beta-gamma-methylene isostere of ATP, but was unaffected by the alpha-beta-methylene isosteres of ADP and ATP, and UTP. At ATP concentrations greater than 100 microM, the inhibitory effects on CPA binding were reversed, until at 2 mM ATP, specific binding of CPA was identical to that seen in controls. Concentrations of ATP greater than 10 mM totally inhibited specific binding. Inclusion of the catabolic enzyme adenosine deaminase in the incubation medium abolished the inhibitory effects of ATP, indicating that these were due to adenosine formation, presumably due to ectonucleotidase activity. The inhibitory effects were also attenuated by the alpha-beta-methylene isostere of ATP, an ectonucleotidase inhibitor. Adenosine deaminase, alpha-beta-methylene ATP (100 microM), and beta-gamma-methylene ATP (100 microM) had no effect on the "stimulatory" phase of binding, although GTP (100 microM) slightly attenuated it. Comparison of the binding of [3H]CPA in the absence and presence of 2 mM ATP by saturation analysis showed that the KD and apparent Bmax values were identical. Examination of the pharmacology of the control and "ATP-dependent" CPA binding sites showed slight changes in binding of adenosine agonists and antagonists. The responses observed with high concentrations of ATP were not observed with GTP, AppNHp, the chelating agents EDTA and EGTA, or inorganic phosphate. The divalent cations Mg2+ and Ca2+ at 10 mM attenuated the stimulatory actions of high (2 mM) concentrations of ATP, whereas EGTA and EDTA (10 mM) enhanced the "stimulatory" actions of ATP. EDTA (10 mM) abolished the inhibitory effects of ATP, indicating a specific dependence on Mg2+ for the inhibitory response. The effects of ATP on [3H]CPA binding were reversible for antagonists but not agonists. The mechanism by which ATP reverses its own inhibitory action on adenosine A-1 radioligand binding is unclear, and from the observed actions of the divalent cations and chelating agents probably does not involve a phosphorylation-dependent process. PMID- 3086506 TI - Secretion of neuron-specific enolase, prolactin, growth hormone, luteinising hormone and follicle stimulating hormone by "functionless" and endocrine-active pituitary tumours in vitro. AB - Secretion of the neuroendocrine marker neuron-specific enolase by 24 pituitary tumours was measured in maintenance tissue culture. Eleven endocrine-active and 13 "functionless" tumours were defined by measurement of prolactin, growth hormone, luteinising hormone (LH) and follicle stimulating hormone (FSH) secretion rates in vitro and the corresponding plasma hormone levels. Measurement of prolactin secretion provided a clear distinction between true prolactinomas and "functionless" tumours causing hyperprolactinaemia by stalk compression (pseudoprolactinomas). A previous report of LH and/or FSH secretion by the majority of "functionless" tumours was confirmed, but plasma levels of LH and FSH were usually normal. It is argued that LH and FSH are not the major hormones secreted by "functionless" tumours. A high production rate of neuron-specific enolase appears to be characteristic of the cell type from which most "functionless" tumours derive. PMID- 3086507 TI - Events in degenerating cat peripheral nerve: induction of Schwann cell S phase and its relation to nerve fibre degeneration. AB - Severance of a peripheral nerve leads to a characteristic series of events in the distal stump, including the dissolution of axons and myelin and the proliferation of Schwann cells within their basal lamina. This study examines the relationship between the spatial-temporal pattern of the induction of the Schwann cell S phase, loss of the structural and functional properties of axolemma, and the clearance of myelin debris in the cat tibial nerve. Nerve transection stimulated a monophasic increase in [3H]thymidine incorporation that peaked at 4 days post transection throughout an 80-mm length of distal stump. Light microscope autoradiography revealed prominent incorporation into Schwann cells of myelinated fibres. Treatment of distal stumps with mitomycin C at the time of nerve transection greatly retarded thymidine incorporation and clearance of myelin debris, but not the time course of axonal degeneration, decline in the synthesis of the major myelin glycoprotein, P0, or the onset of ovoid formation. Nerve transection also greatly reduced the specific uptake of [3H]saxitoxin (STX), a ligand which binds to voltage-sensitive sodium channels. Binding in the distal stump fell precipitously to 20% of the normal at 4 days post-transection, concurrent with the peak of thymidine incorporation. This low level of binding was maintained for periods of up to 70 days, demonstrating that some STX binds to structures other than axons in denervated distal stumps. Prior treatment with mitomycin C delayed the loss of specific STX binding. In conclusion, these studies suggest that: Schwann cell DNA replication and/or mitosis regulates other events during Wallerian degeneration, including myelin degeneration, catabolism of P0 and the clearance of sodium channels from nodal axolemma; the decline in P0 synthesis and/or shift to synthesis of less extensively processed P0 is independent of the induction of Schwann cell S phase; and Schwann cells enveloping myelinated axons enter S phase within a 24-h period throughout the entire 80-mm length of distal stump. PMID- 3086508 TI - Essential monitoring examined through different lenses. AB - When we ask, what renders essential a particular monitoring approach during routine anesthesia for a healthy patient, perplexing questions, rather than satisfying answers, are raised. I have examined these questions with the help of three lenses that focus on the relationship between the outcome of anesthesia and the detection, and thus correction, of abnormalities during anesthesia. The first lens looks at whether the monitoring modalities accepted by anesthesiologists as "minimal" and "essential" have been scientifically proven to affect outcome from routine anesthesia. A second lens views how well monitors reveal the integrity of the organism and its components. Currently available monitors describe the output of cells or organs but relay little information about the viability of cells. Thus, they describe the symptoms rather than the causes of the pathophysiology related to anesthesia. Today's monitors also measure input, for example, the supply of oxygen, perhaps the most routinely measured of all the variables. The third lens looks at whether there are nonclinical influences on monitoring practice. This lens views the gap between recognizing monitoring possibilities and adopting them clinically; it also views geographic differences in monitoring, as well as social pressures exerted through legal proceedings. Finally, currently recognized essential monitors such as blood pressure measurement, electrocardiography, and oxygen analysis are mentioned, and candidates for inclusion in the list of essential monitors, such as oximeters, capnographs, and the automated record, are discussed. PMID- 3086510 TI - Cutaneous gas monitors. PMID- 3086509 TI - History of blood gas analysis. III. Carbon dioxide tension. AB - The measurement of carbon dioxide tension (Pco2) owes its development to the 1952 polio epidemics in Copenhagen and the United States, during which artificial ventilation was first widely and effectively used and it was necessary to assess its effectiveness. Pco2 had been determined by various "bubble methods" in which carbon dioxide (CO2) was measured in gas equilibrated with blood at body temperature, or by one of two methods using the manometric apparatus of Van Slyke: interpolation on a plot of CO2 content versus equilibration gas Pco2 or use of the Henderson-Hasselbalch equation to calculate Pco2 from pH and plasma CO2 content. In 1954 Richard Stow described a CO2 electrode--a new concept--using a rubber membrane permeable to CO2 to separate a wet pH and reference electrode from the blood sample. This was the first membrane electrode, a device now used in hundreds of different ways. Severinghaus developed Stow's electrode, stabilizing it with a bicarbonate-salt solution and a spacer. The CO2 electrode concept had occurred to Gesell in 1925, but for measurement of gas only, and to Gertz and Loeschcke, who were unaware of the Stow-Severinghaus electrode, in 1958. The development of the CO2 electrode terminated the use of bubble methods, the Van Slyke methods, and the Astrup technique and at the same time reinforced the Astrup-Siggaard-Andersen acid-base analytic theory. PMID- 3086512 TI - End-expiratory carbon dioxide measurement as an estimate of alveolar carbon dioxide tension. PMID- 3086511 TI - Conjunctival oxygen tension and its relationship to arterial oxygen tension. AB - Using a miniaturized Clark electrode embedded in a polymethylmethacrylate eyepiece, we measured transconjunctival oxygen tension (PcjO2) in 5 healthy volunteer subjects at multiple levels of steady-state isocapnic hypoxia, normoxia, and hyperoxia. PcjO2 was linearly related to arterial oxygen tension (PaO2) as PaO2 ranged from 28 to 205 mm Hg (PcjO2 = 0.59 PaO2 + 0.36 mm Hg; r = 0.94; standard error of the estimate = 7.09 mm Hg). However, the relationships between PcjO2 and PaO2 varied significantly among subjects. Whereas the overall mean ratio of PcjO2 to PaO2 was 0.59, the mean ratio for subjects ranged from 0.47 to 0.79 and was significantly different among subjects (P less than 0.0001). The time response of the electrode to a step change in oxygen tension in vitro was exponential, with a 90% response time of 38 seconds after a lag of 3.7 seconds. The time responses to in vivo changes in oxygen tension were also exponential. From hypoxia to normoxia, 90% response time was 45.0 seconds after a lag of 5.1 seconds; from room air to hypoxia, 90% response time was 72.4 seconds after a lag of 30.3 seconds; from room air to hyperoxia, 90% response time was 87.2 seconds after a lag of 6.8 seconds. We conclude that, although PcjO2 measured by a miniaturized Clark electrode is linearly related to PaO2 in healthy subjects, variation in the relationship of PcjO2 to PaO2 among individuals will prevent precise estimation of PaO2 for any individual unless subject-specific calibration is performed. PMID- 3086513 TI - Aminergic modulation in lobster stomatogastric ganglion. I. Effects on motor pattern and activity of neurons within the pyloric circuit. AB - We investigated the effects of dopamine, octopamine, and serotonin on the motor output of the pyloric circuit in the stomatogastric ganglion of the lobster, Panulirus interruptus. Amines were bath applied at concentrations from 10(-8) to 10(-4) M, and the responses of the six classes of pyloric neurons were monitored both intracellularly and extracellularly. Each amine modified the pyloric motor pattern in a specific way. In addition, dopamine and octopamine were each able to produce different motor patterns at different concentrations. Amine effects on pyloric neurons included initiation and enhancement or inhibition of spike activity, changes in the phase relationships of neurons, and changes in the cycle frequency of the pyloric rhythm. These results show that the motor pattern produced by this well-studied central pattern generator circuit is highly plastic and can be modulated by endogenous biogenic amines. PMID- 3086514 TI - Aminergic modulation in lobster stomatogastric ganglion. II. Target neurons of dopamine, octopamine, and serotonin within the pyloric circuit. AB - In the preceding paper, we describe how dopamine, octopamine, and serotonin modulate the neural circuit generating a well-described motor pattern, the pyloric rhythm of the stomatogastric ganglion in the spiny lobster, Panulirus interruptus. In this paper, we identify the neurons within the pyloric circuit that are directly affected by each amine. We accomplished this by isolating each pyloric neuron from all known synaptic input, using a combination of Lucifer yellow photoinactivation of presynaptic neurons and pharmacological blockade by pyloric neurotransmitters. Dopamine, octopamine, and serotonin were bath applied to the preparation, and the responses of synaptically isolated neurons were recorded. Each amine had a unique constellation of effects on the neurons of the pyloric circuit. Almost every neuron in the circuit was directly affected by each amine. Dopamine and octopamine modulated every neuron, whereas serotonin affected four of the six cell types. Each amine had multiple effects among pyloric neurons including the induction of endogenous rhythmic bursting activity, initiation or enhancement of tonic firing activity, and inhibition accompanied by hyperpolarization. All three amines induced rhythmic bursting in one neuron (the AB neuron), but the form of the underlying slow-wave membrane-potential oscillations was different with octopamine than with dopamine and serotonin. Our knowledge of the effects of each amine on each pyloric neuron, combined with the extensive knowledge of the synaptic organization of the pyloric circuit, has allowed us to explain qualitatively the major aspects of the unique variants of the pyloric motor rhythm that each amine produces in the synaptically intact circuit. PMID- 3086515 TI - Development of serotonin-containing neurons in Drosophila mutants unable to synthesize serotonin. AB - We have initiated a study of the CNS of mutant Drosophila melanogaster larvae carrying a genetic deletion of the gene Ddc that encodes the enzyme dopa decarboxylase (DDC). The two major objectives of this study were (1) to ascertain that the DDC encoded by the gene Ddc was the only decarboxylase utilized in serotonin (5HT)-containing neurons and (2) to determine the effect of DDC deficiency on the development of 5HT-immunoreactive neurons. CNSs of wild-type larvae and of larvae genetically deficient for the gene Ddc were processed for serotonin immunocytochemistry using a monoclonal antibody against 5HT. The pattern of 5HT immunoreactivity in the wild-type and the Ddc-deficient CNS is compared. In contrast to the wild-type, 5HT immunoreactivity is absent in the Ddc deficient CNSs. The lack of immunocytochemically detectable 5HT in the mutant CNSs is consistent with the idea that the DDC encoded by the gene Ddc is utilized in 5HT-containing neurons. To study the development of neurons committed to the 5HT differentiation pathway in the absence of 5HT, we used a second biochemical property characteristic of 5HT-containing neurons, the ability to take up 5HT. CNSs from mutant animals were incubated in exogenous 5HT and the accumulated 5HT detected immunocytochemically. Neurons capable of selective 5HT uptake were present in the mutant CNSs in the same pattern as the 5HT-immunoreactive neurons in the wild-type CNS. This result suggests that the presumed inability to synthesize 5HT does not preclude differentiation of other normal biochemical properties of 5HT-containing neurons. PMID- 3086516 TI - Enkephalin convertase: localization to specific neuronal pathways. AB - 3H-Guanidinoethylmercaptosuccinic acid (GEMSA) selectively labels the carboxypeptidase B-like enzyme enkephalin convertase (EC) in rat brain tissue sections. We have used autoradiography with 3H-GEMSA to map membrane-bound EC in the rat forebrain and, in conjunction with lesioning techniques, to localize EC to specific neuronal pathways. The highest levels of EC are in the median eminence. High levels of EC also occur in the hypothalamic magnocellular nuclei, in several nuclei of the amygdala, the lateral septum, and the bed nuclei of the stria terminalis. Knife-cut lesions of the stria terminalis increase EC posterior to the lesion in the stria and deplete EC from the stria adjacent to the bed nucleus, suggesting that EC, like enkephalins, is axonally transported within the stria terminalis. Ibotenic acid lesions of the caudate nucleus destroy binding in the substantia nigra pars reticulata ipsilateral to the lesion, suggesting that nigral EC is associated with axons originating in the caudate nucleus. We have also mapped EC in detail in the hippocampus. EC levels are highest near pyramidal cells of CA 3-4 and the dentate gyrus granule cells. Quinolinic acid lesions destroy both the granule and pyramidal cells and destroy all of the 3H-GEMSA labeling except for a small amount in the molecular layer of the dentate gyrus. Selective destruction of CA 3-4 pyramidal cells with kainic acid eliminates EC in the pyramidal cell region. Destruction of granule cells of the dentate gyrus with colchicine depletes binding in the dentate gyrus without any change in the area surrounding field CA 3-4. High levels of 3H-GEMSA binding are present in the hippocampus at least 3 d before birth. These observations suggest that in the hippocampus the majority of EC is associated with pyramidal cells, which have not been shown to contain enkephalins. 3H-GEMSA autoradiography of the trigeminal ganglion localizes EC to the sensory neurons and not to white matter tracts there. These studies demonstrate that while EC is contained in enkephalinergic pathways, it is also present in some neurons that do not contain enkephalins. PMID- 3086518 TI - Animal model of subarachnoid hemorrhage. PMID- 3086517 TI - Ascorbic acid increases the thyrotropin-releasing hormone content of hypothalamic cell cultures. AB - Thyrotropin-releasing hormone (TRH) is one of many COOH-terminal alpha-amidated neuropeptides. Recent work with the intermediate pituitary has indicated that ascorbate is a required cofactor for the COOH-terminal alpha-amidation of alpha melanotropin. This is consistent with the ascorbate requirement of an enzyme found in pituitary and hypothalamus capable of converting peptides with a COOH terminal glycine (-X-Gly) to alpha-amidated molecules (-H-NH2). Thus, it has been proposed that COOH-terminal glycine-extended TRH (TRH-Gly) may be the direct precursor to TRH. In the present study, primary hypothalamic cultures supplemented with ascorbate for 7 d contained two- to threefold more TRH immunoactivity (amide-specific) than cultures maintained without ascorbate. A dose-response experiment indicated that 20 microM ascorbate was capable of producing 50% of the maximum observable increase in culture TRH immunoactivity; this concentration is similar to the Km value for ascorbate uptake obtained in adrenal chromaffin and pituitary cells. A stereoisomer of ascorbate, D isoascorbate, was also capable of producing an increase in TRH immunoactivity, but oxidized ascorbate was not. Recent studies have shown that the amidation enzyme from pituitary is capable of utilizing both L-ascorbate and D-isoascorbate but is incapable of utilizing oxidized ascorbate. The culture extracts were analyzed further by reversed-phase high-performance liquid chromatography; the increased TRH immunoactivity observed in extracts of cultures maintained in ascorbate comigrated with standard synthetic TRH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086519 TI - The effect of mannitol on cerebral white matter water content. AB - The authors have studied the effect of a low-dose (0.28 gm/kg) bolus infusion of mannitol on brain water in man. In eight patients with severe head injury, small pieces of subcortical white matter were taken at craniotomy both before and after infusion of mannitol. The tissue specific gravity was measured using a graduated specific-gravity column, and from it the brain water content was calculated. White matter specific gravity rose from a mean (+/- standard error of the mean) of 1.0325 +/- 0.0012 before mannitol infusion to 1.0352 +/- 0.0011 after mannitol administration, and the brain water content fell from a mean of 80.94% +/- 2.5% to 75.28% +/- 2.3%. The differences were significant (p less than 0.01). This study shows that, after head injury in man, mannitol increases the white matter specific gravity and probably does so by reducing brain water. PMID- 3086520 TI - High yield synthesis of 6-[18F]fluoro-L-dopa. AB - The radiofluorination of L-dopa with [18F]F2 was investigated with the purpose of improving the yield of 6-[18F]fluoro-L-dopa. When boron trifluoride was added to the reaction mixture in hydrogen fluoride (HF), the yield was increased threefold. Nine millicuries of 6-[18F]fluoro-L-dopa were produced from 100 mCi [18F]F2 routinely and reliably after 2 hr of preparation. If acetonitrile or water were substituted for HF, little or no 6-fluoro-L-dopa was made. PMID- 3086521 TI - Nuclear medicine in the prospective payment environment: the need for individual and group initiatives. PMID- 3086522 TI - Technetium-99m labeling of murine monoclonal antibody fragments. AB - F(ab')2 fragments of several murine monoclonal antibodies have been labeled with 99mTc by a direct, pretinning method. The fragments were incubated with stannous ions overnight to split disulfide groups--a process which converts dimeric F(ab')2 to monomeric fragments. The pretinned fragments were then either directly labeled with 99mTc, frozen for subsequent labeling, or lyophilized to make kits for 99mTc-labeling at some later date. The 99mTc-labeled fragments were shown to be stable against transchelation when challenged with ethylenediaminetetraacetic acid, retained immunoreactivity, and were capable of binding to human tumor xenografts in nude mice. PMID- 3086523 TI - Service line management. New opportunities for nursing executives. AB - The benefits of service line management are crucial to hospitals' survival in today's changing health care environment. Nursing executives can direct activities affecting every aspect of health care delivery in the role of service line manager. These activities include such important components as standards of care, utilization review, program development, physician relations, and quality practice issues. PMID- 3086524 TI - A comparison of patient acuity and nursing resource use. AB - An analysis of patient records in four different DRG categories estimated direct nursing care requirements. The evaluation of these results showed a great range in direct hours of nursing care, as well as resultant cost of nursing care within and among the DRG categories. Nursing resource use is widely fluctuating based on acuity levels, length of stay, and DRG category. Thus, it was concluded the variables inherent in a model to predict cost rely on determinants of the functional needs of the individual patient. PMID- 3086525 TI - Serum levels of coenzyme Q10 and lipids in patients during total parenteral nutrition. AB - Serum levels of coenzyme Q10 (CoQ10) as well as lipids were determined in patients during total parenteral nutrition (TPN). The mean CoQ10 levels (M +/- SD) were 0.77 +/- 0.30 microgram/ml for 108 normal subjects and 0.59 +/- 0.35 microgram/ml for 95 patients before TPN. The mean CoQ10 level of the patients decreased significantly to 0.35 +/- 0.23 microgram/ml one week after the start of TPN, and then remained almost unchanged during TPN for up to 6 weeks. When the patients receiving TPN (TPN patients) were grouped according to their clinical diagnoses, the mean CoQ10 level of patients with cancer was significantly lower than that of the other patients without cancer in 4 week therapy, but there was no difference in the levels between the patients with and without diseases of the gastrointestinal tract. Serum levels of total cholesterol (T-Chol) and esterified cholesterol in TPN patients also declined below their respective normal ranges, but not to the same extent in comparison to CoQ10. The levels of triglycerides (TG), phospholipids (PL), non-esterified fatty acids, low density lipoproteins, very low density lipoproteins, chylomicrons, and cholesterol in the high density lipoprotein fraction in serum of TPN patients were within their normal ranges. The levels of CoQ10 in TPN patients were correlative to those of T-Chol, TG, and PL, and decreased rapidly prior to the latter levels. PMID- 3086526 TI - Changes of amino acids composition and relative digestibility of lysozyme in the reaction with alpha-dicarbonyl compounds in aqueous system. AB - Lysozyme was reacted with xylose, methyl linoleate, glyoxal, methylglyoxal and diacetyl in an aqueous system (50 degrees C, pH 6.0), and browning, polymerization, changes of amino acids composition and relative digestibility of the browned lysozyme were investigated. Browning intensity as well as degree of polymerization of lysozyme in the reaction with alpha-dicarbonyls was higher than with xylose or methyl linoleate. After 10 days of reaction with alpha dicarbonyls, the amino acid composition of lysozyme was markedly affected; i.e., 30-70% of lysine, 40-50% of tryptophan and 90% of arginine were lost respectively. By digestion with a pepsin-pancreatin system, it was observed that the relative digestibility of lysozyme reacted with dicarbonyl was lower than that of lysozyme reacted with methyl linoleate or xylose. PMID- 3086527 TI - The in vitro effect of gold complexes on bone resorption. AB - Mouse calvaria were maintained in organ culture without serum additives. The effects of three gold complexes--aurothioglucose, aurothiomalate, and auranofin- on active bone resorption (45Ca release) and hydroxyproline synthesis were determined. The influence of these compounds on DNA and protein synthesis and lysosomal enzyme release from calvaria was also assessed. All gold complexes reduced bone resorption to some extent, with auranofin being the most potent within a narrow concentration range (10(-6) M). This concentration of auranofin also significantly inhibited collagen synthesis, although DNA and protein synthesis were unaffected. None of the compounds tested appeared to mediate their action via significant inhibition of lysosomal enzyme release. PMID- 3086528 TI - [Cochlear damage by nitromin or cisplatin and the influence of steroid hormone]. PMID- 3086529 TI - Nutritional supplementation for cystic fibrosis. PMID- 3086530 TI - Gonadal dysgenesis and gonadoblastoma in situ in a female with Fraser (cryptophthalmos) syndrome. PMID- 3086532 TI - Development of erythrocytic merozoites to gametocytes in chickens recovered from sporozoite infection with Leucocytozoon caulleryi. PMID- 3086531 TI - Fetal growth, major malformations, and minor anomalies in infants born to women receiving valproic acid. AB - The association of fetal and neonatal distress, birth measurements, major malformations, and minor anomalies was studied prospectively in 14 infants of women with epilepsy who were receiving valproic acid (VPA) monotherapy and in 12 infants of women with epilepsy who were receiving VPA in combination with other anticonvulsant drugs. Comparison was made with 26 matched-pair controls and 116 controls from a larger study of antiepileptic drugs. During the first trimester, total VPA serum concentrations were well above therapeutic levels (100 to 184 micrograms/ml) in two women receiving high VPA doses (2000 and 1500 mg daily). Although dosage remained the same, serum concentrations decreased during pregnancy to therapeutic levels (33.9 to 57.0 micrograms/ml). The VPA percent free fraction increased in the third trimester and was threefold higher at birth. Almost half of the infants exposed to VPA monotherapy were distressed during labor, and 28% had low Apgar scores. Fetal and neonatal distress may be caused by the high VPA percent free fraction during labor and at birth. Mean body measurements at birth after VPA monotherapy were comparable to those in the matched control group, but were reduced in the group of infants receiving VPA combination therapy. Four infants exposed to VPA monotherapy were born with major malformations. The median number of minor anomalies was four times higher in infants whose mothers received VPA alone or VPA combination therapy than in controls. Seven infants had a pattern of craniofacial and digital anomalies that was distinctly different from that observed after in utero exposure to other anticonvulsant medications. The occurrence of major malformations and the number of minor anomalies may be dose related. PMID- 3086533 TI - A 42 month clinical evaluation of glutaraldehyde pulpotomies in primary teeth. PMID- 3086534 TI - [An evaluation of substrate-labeled fluorescent immunoassay (SLFIA method) by using pharmacokinetic parameters of valproic acid]. PMID- 3086535 TI - Effects of dietary fat on drug metabolism. AB - The fact that nutriture affects drug metabolism and drug action in laboratory animals is undisputable. Activation or detoxification of drugs and potential carcinogens can also be modified by diet. The quantity and quality of dietary fat affects lipid composition and physical characteristics of biological membranes and enzymatic activity of several components of the drug metabolizing enzyme system. These changes have been associated with alterations in the physiological response to drugs and to the resulting mutagenicity and carcinogenicity of procarcinogens. It is suggested by these data that dietary fat, by altering fatty acid composition of biological membranes, alters the physical and biochemical characteristics of these membranes, thereby directly affecting drug entrance into the membrane; the stability of the membrane; the potential for lipid peroxidation; and the activity of the phospholipid dependent enzymes associated with these membranes. The fact that these membrane associated changes can occur rapidly and that brief periods of fatty acid deprivation can profoundly affect the inducibility of these enzymes by xenobiotics suggests that the potential for drug-nutrient interactions exists in the absence of frank nutrient deficiency states. PMID- 3086536 TI - Interaction of aflatoxin B1 with bacterial DNA: possible relationship to bacteriophage induction in lysogenic Bacillus megaterium. AB - Studies were conducted to determine possible interactions between aflatoxin B1 and deoxyribonucleic acid (DNA) and induction of bacteriophage formation in lysogenic Bacillus megaterium NRRL-B-3695. At pH 7.4, the spectrophotometric characteristics of B1 with various concentrations of calf thymus DNA were altered with both a hypochromic shift and a shift of the wavelength for maximum absorbance of the toxin. Aflatoxin B1 apparently interacted with DNA as indicated by spectrophotometric analysis and ultrafiltration studies. Under alkaline conditions (pH 10.0), spectrophotometric characteristics of this interaction were altered from those observed at pH 7.4. Toxin incubated at pH 7.4 could induce bacteriophage formation but failed to do so at pH 10. Preincubation of toxin with calf thymus DNA did not block subsequent induction. It is proposed that a bacterial DNA-toxin interaction, involving an alkaline-labile bond of aflatoxin B1, is necessary to cause induction of bacteriophage formation in lysogenic B. megaterium. PMID- 3086537 TI - Effects of mixed-function oxidase and aflatoxin B1 on lysogenic and indicator strains of Bacillus subtilis. AB - The present study was conducted to determine the effects of metabolized aflatoxin B1 (via a mammalian liver mixed-function oxidase system) and native aflatoxin B1 upon induction of bacteriophage in Bacillus subtilis and growth of B. subtilis. A lysogenic strain of B. subtilis (BDS-1, phi 105) and an indicator strain of this species (DBS-1) were utilized in the present experiment. Lysogenic cultures were incubated for various lengths of time in the presence of either native or metabolized toxin, and plaque-forming units were determined. Identical experiments were conducted with the indicator strain and colony-forming units were determined. At a native toxin concentration of 25 micrograms/ml of medium, the maximum number of plaque-forming units was induced in lysogenic cells. However, when cells were incubated in the presence of aflatoxin B1 and mixed function oxidase, neither plaque-forming units nor colony-forming units could be detected from lysogenic or indicator cells, respectively. This organism is apparently much more susceptible to inhibition of cellular replication than to lysis via bacteriophage induction. Thus, from the present study and from previously reported research, differences in susceptibility to native and metabolized aflatoxin B1 exist among species of Bacillus. PMID- 3086538 TI - Sodium valproate, but not ethosuximide, produces use- and voltage-dependent limitation of high frequency repetitive firing of action potentials of mouse central neurons in cell culture. AB - Effects of the anticonvulsant drugs sodium valproate (NaVP) and ethosuximide (ES) on mouse central (spinal cord and cortical) neurons in primary dissociated cell culture were studied using intracellular recording techniques. Drug effects on two properties of the neurons were assayed: the ability to sustain high frequency repetitive firing (SRF) of sodium-dependent action potentials, a voltage sensitive nonsynaptic membrane property; and the amplitude of responses to iontophoretically applied gamma-aminobutyric acid (GABA), a postsynaptic effect of this inhibitory amino acid neurotransmitter. At concentrations equivalent to the clinically useful therapeutic range in cerebrospinal fluid (6-200 microM), NaVP limited SRF to a few action potentials in both spinal cord and cortical neurons during long (450 msec) depolarizing current pulses. The limitation of SRF was paralleled by use-dependent reduction of maximal rate of rise (Vmax) of the action potentials and prolongation of recovery of Vmax from inactivation. This action was similar to limitation of SRF produced by phenytoin and carbamazepine. The 2-en-metabolite of NaVP, sodium 2-propyl, 2-pentenoate, did not limit SRF at 12 to 120 microM. However, the diphenyl analog of NaVP, sodium diphenylacetate, limited SRF at concentrations between 4.7 to 23.5 microM. ES did not affect SRF at concentrations up to 700 microM. At concentrations of 120 to 1000 microM, including the upper limit of therapeutic range, NaVP did not affect postsynaptic GABA responses in 80% of spinal cord neurons. In the remaining 20%, GABA responses were augmented less than 33%. ES reduced slightly (22%) GABA responses at a high concentration (700 microM). These findings suggest that limitation of SRF may be an important cellular mechanism by which NaVP, but not ES, exerts anticonvulsant efficacy and that neither ES nor NaVP have anticonvulsant action by enhancing postsynaptic GABA action. PMID- 3086539 TI - Regulation of rat heart membrane adenylate cyclase by magnesium and manganese. AB - Rat myocardial adenylate cyclase activity was characterized with respect to its regulation by Mg and Mn. Myocardial adenylate cyclase is activated by both free divalent cations at concentrations greater than that required to form the active cation-ATP substrate. Six separate lines of evidence indicate that Mg and Mn are distinguishable from each other as regulators of adenylate cyclase: 1) After solubilization, adenylate cyclase is preferentially stimulated by Mn. 2) High concentrations of Mn (greater than 1 mM)--but not Mg--have an additional effect on particulate adenylate cyclase to attenuate basal adenylate cyclase activity and to render the membranes refractory to stimulation by isoproterenol and guanyl 5'-yl-imidodiphosphate [Gpp(NH)p]. This inhibitory property of Mn is lost after solubilization. 3) Isoproterenol enhances the affinity of adenylate cyclase for Mg but not for Mn. 4) Stimulation of adenylate cyclase by Gpp(NH)p is consistent with a simple single-site interaction of Gpp(NH)p with the adenylate cyclase complex in the presence of Mg. In contrast, Mn exposes a broad, 3-log-order, stimulatory response to Gpp(NH)p, 0.1 to 100 microM. After solubilization, Mn allows Gpp(NH)p to stimulate adenylate cyclase by simple Michaelis-Menten kinetics as shown for Mg in particulate and solubilized preparations. 5) The lag associated with inhibition of forskolin-sensitive adenylate cyclase is diminished by Mg but not by Mn. 6) Activation of membrane-bound adenylate cyclase by forskolin is consistent with an action at a single, high-affinity site. After solubilization, activation by forskolin is biphasic, with both high- and low affinity components becoming apparent. The adenylate cyclase response to forskolin at the low-affinity site is greater with Mn than with Mg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086541 TI - Distribution and metabolism of nitroglycerin and its metabolites in vascular beds of sheep. AB - The disposition of nitroglycerin (NTG) and its metabolites has been examined in anesthetised sheep after infusion of 0.4, 5.7 and 22.1 micrograms of NTG/min/kg through the right femoral vein. Several blood samples were collected from the left ventricle, pulmonary artery, left femoral artery, left femoral vein, portal vein and hepatic vein. Significant extraction of NTG across all vascular beds was demonstrated. The extraction was shown to be dose-dependent reflecting hemodynamic and metabolic events. Evidence for metabolism of NTG was provided by the formation of the dinitro and mononitrate metabolites. A preliminary study also showed that administration of the dinitroglycerin significantly impaired NTG metabolism across the hind leg without affecting markedly the hemodynamic response associated with the infusion of NTG. PMID- 3086540 TI - Qualitative and quantitative comparison of the cardiac effects of encainide and its three major metabolites in the dog. AB - We have evaluated the electrophysiologic effect of encainide and its three major metabolites, O-demethyl encainide, 3-methoxy-O-demethyl encainide and N-demethyl encainide in an anesthetized dog model. Our results support previous reports that O-demethyl encainide and 3-methoxy-O-demethyl encainide are both more potent than encainide in the depression of conduction. We also have shown that N-demethyl encainide is of about equal potency to encainide. Whereas the major differences between these compounds is primarily one of potency, there are some qualitative differences. Although O-demethyl encainide did not change the ventricular or atrial effective refractory periods significantly, 3-methoxy-O-demethyl encainide and N-demethyl encainide prolonged both. Encainide increased the atrial effective refractory period but did not produce significant changes in the ventricular refractory period. These data support previous suggestions of an important role for these metabolites as modulators of the clinical efficacy of encainide. PMID- 3086542 TI - Uptake of lipophilic model compounds into the isolated perfused rat epididymal adipose tissue. AB - Uptake of xenobiotics into isolated perfused rat adipose tissue was studied. Aorta and vena cava were cannulated and ligations were placed so that only an epididymal fat pad was perfused. Perfusion experiments were performed in situ and nonrecirculating, for up to 350 min, with Krebs-Ringer bicarbonate buffer containing 4% serum albumin. The functionality of the preparation was tested by an after-perfusion with methylene blue as well as with the volume and mass balances. Formation of edema was not a problem under the experimental conditions used. The following model compounds were used at influx concentrations of 2 to 8 microM: thiopental, imipramine, chlorpromazine, 1,1-bis-(p-chlorophenyl)-2,2 dichloroethane (DDE) and 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB). Uptake was determined during the experiments using the arteriovenous difference and after the experiments by direct determination in the perfused fat pad. All five model compounds were taken up readily. Rate of uptake tended to decrease initially and to reach a constant value. Only with 6-CB was the difference between initial and terminal rate considerable. Mean uptake fraction was: thiopental, 38 +/- 8%; imipramine, 69 +/- 4%; chlorpromazine, 85%; DDE, 56%; and 6-CB, 13 +/- 1%. Thus, imipramine and chlorpromazine, which do not accumulate in adipose tissue in vivo, are even taken up more rapidly into the isolated perfused adipose tissue than is thiopental. The difference between these two experimental situations is therefore not due to a permeability barrier, but rather to factors outside the adipose tissue, such as competing nonadipose tissues present in vivo only. For the neutral, insoluble and almost totally albumin-bound compounds, DDE and 6-CB, albumin may act as an additional binding competitor that inhibits adipose tissue uptake. PMID- 3086543 TI - Prolactin response to TRH in depression. AB - We studied the prolactin response to TRH in 53 unmedicated psychiatric inpatients. The prolactin response of females was significantly greater than the response of male subjects. There was no significant difference in the prolactin response to TRH between depressed patients and those with other psychiatric diagnoses. There was no significant relationship between the prolactin response to TRH and the severity of depression, the TSH response to TRH or the resistance to suppression of cortisol secretion by dexamethasone. PMID- 3086544 TI - Cup-patch ileocystoplasty in the treatment of bilharzial contracted bladder. PMID- 3086545 TI - Fetal growth response to total parenteral nutrition in pregnancy. A case report. AB - Although clinical experience with total parenteral nutrition (TPN) in pregnancy is accumulating, assessment of the fetal growth response to this therapy has been limited primarily to birth weight. We performed serial ultrasonographic measurements of the fetal biparietal diameter (BPD), femur length (FL) and abdominal circumference (AC) in a patient who received TPN because of chronic malnutrition. BPD and FL were within normal limits before and after TPN. Consistent with asymmetric growth retardation, the AC was low prior to TPN and increased significantly after TPN was administered. Estimated fetal weight increased accordingly. These data suggest that TPN can reverse subnormal fetal growth secondary to maternal nutritional deprivation. PMID- 3086546 TI - Comparative trial of shampoos for treatment of head infestation. PMID- 3086547 TI - Parasites in Britain: a review. PMID- 3086548 TI - Community health councils--a nurse's contribution. PMID- 3086549 TI - Problems of drug treatment in the elderly. PMID- 3086551 TI - Sport and health. PMID- 3086550 TI - Spinal cord injuries. PMID- 3086552 TI - Contraception among female students in the University of Benin. PMID- 3086553 TI - Attitudes of adults to sanitation facilities in Ibadan. PMID- 3086554 TI - Family influence on incidence of intestinal parasites among Nigerian children. PMID- 3086555 TI - Pulmonary tuberculosis in Nigeria. PMID- 3086556 TI - The lysine pathway as a target for a new genera of synthetic antibacterial antibiotics? AB - Unsaturated analogues of diaminopimelic acid have been synthesized. The amino acids were designed so that they would be reversible or irreversible inhibitors of both of the two last enzymes of the lysine pathway. The compounds were tested with meso-diaminopimelate decarboxylase. trans-3,4-Didehydrodiaminopimelic acid (2) was found to be the most potent inhibitor. The antibacterial activities did not correlate with enzyme inhibiting activities. 4-Methylenediaminopimelic acid 4 showed strong antibacterial properties. It is suggested that L,L-diaminopimelate epimerase could be the target enzyme. PMID- 3086557 TI - Synthesis and rat lens aldose reductase inhibitory activity of some benzopyran-2 ones. AB - A number of 4,7-disubstituted benzopyran-2-ones were synthesized and evaluated for crude rat lens aldose reductase inhibitory activity. Substituents on position 4 included CH3, CO2H, CH2CO2H, CH = CHCO2H, and CH2CH2CO2H. The aromatic substituents included OH, OCH3, OCOCH3, CH2CH3, and Cl. Also included in the study were 3-oxo-3H-naphtho[2,1-b]pyran-1-acetic, 2-oxo-2H-naphtho[1,2-b]pyran-4 acetic, and 1-naphthylacetic acids. The benzopyran and naphthopyran derivatives were prepared by the classical von Pechmann reaction. General structure-activity relationships reveal that optimal enzyme inhibitory activity is displayed by those compounds possessing the acetic acid moiety. For example, the most potent derivative, 3-oxo-3H-naphtho[2,1-b]pyran-1-acetic acid with an IC50 of 0.020 microM, is as potent as sorbinil (IC50 = 0.017 microM) in the crude rat lens aldose reductase assay. PMID- 3086558 TI - Antiinflammatory activity of substituted 6-hydroxypyrimido[2,1-f]purine 2,4,8(1H,3H,9H)-triones. Atypical nonsteroidal antiinflammatory agents. AB - A novel class of antiinflammatory drugs, which are substituted derivatives of the fused tricyclic system 6-hydroxypyrimido[2,1-f]purine-2,4,8(1H,3H,9H)-trione, is described. Synthetic procedures and structure determination with the assistance of X-ray crystallography are discussed. Semiempirical molecular orbital calculations are used to investigate the relative stability of the possible isomers and tautomers of the title compounds. A biological profile of the class, and of several of the more potent analogues, in several antiinflammatory models, including the adjuvant-induced arthritis and the collagen II models, is defined. Several members of the class are shown to possess extremely low ulcerogenic effects in spite of exhibiting cyclooxygenase inhibition. A preliminary bioavailability study of two of the lead structures is presented. The compounds 6 72 appear to constitute a class of drugs that shows interesting potential antiarthritic activity and also exhibits an activity profile different from that of the standard classical NSAI drugs, as determined by a comparison of the profile of this class of drug with that of several standard agents. Certain findings from toxicological studies have precluded the further development of compounds within this group, although related structural types are being investigated. PMID- 3086559 TI - 7-Aroyl-2,3-dihydrobenzo[b]furan-3-carboxylic acids and 7-benzoyl-2,3 dihydrobenzo[b]thiophene-3-carboxylic acids as analgesic agents. AB - The synthesis of a series of 7-aroyl-2,3-dihydrobenzo[b]furan-3-carboxylic acids and 7-benzoyl-2,3-dihydrobenzo[b]thiophene-3-carboxylic acids is described. The isomeric 4-benzoyl-1,3-dihydrobenzo[c]furan-1-carboxylic acid was also prepared. Compounds were evaluated for analgesic activity in the mouse phenyl-p-quinone induced writhing test. Selected compounds were tested for their ability to produce gastric damage in fasted mice and for inhibition of prostaglandin synthetase activity in vitro. Zomepirac was used as a reference. Structure activity relationships are discussed. One of the compounds, 7-benzoyl-5-chloro 2,3-dihydrobenzo[b]furan-3-carboxylic acid (2c), combined potent analgesic activity with low gastric irritancy. PMID- 3086561 TI - Vascular access in the cancer patient. AB - Patients requiring frequent blood sampling and/or frequent intravenous fluid administration can be difficult to manage clinically once peripheral veins become exhausted. Not only can peripheral vascular access be difficult in these patients, but patients begin to dread the attempts at blood sampling and intravenous line placement more than the chemotherapy regimen.At Howard University Hospital, several different types of commercial vascular access devices have been employed that afford reliable and dependable use in cancer patients requiring chemotherapy and blood monitoring. With the increased use of these devices, one unpleasant aspect in the management of the cancer patient, that of repeated attempts at vascular access, can be eliminated. PMID- 3086560 TI - Pyruvate attenuation of hypoxia damage in isolated working guinea-pig heart. AB - Function and various parameters of myocardial substrate and energy metabolism were measured in preload-controlled isolated working guinea-pig hearts perfused with normoxic (95% O2) and hypoxic (30 to 45% O2) Krebs-Henseleit buffers ([Ca2+] = 1.25 mM). Energy-yielding substrates were glucose, pyruvate, lactate, and fatty acids (acetate, octanoate). Hypoxia typically produced an increase in coronary flow but a fall in cardiac oxygen uptake (MVO2); left ventricular pressure and work parameters as well as myocardial high energy phosphate levels were decreased while the releases of adenosine plus inosine (V (Ado + Ino)) and lactate were increased. Extra pyruvate (1 to 5 mM) as compared to physiologic concentrations of pyruvate (0.2 mM) produced a relative stabilization of left ventricular pressure and work parameters combined with an attenuation of V (Ado + Ino) provided 5 to 10 mM glucose was the cosubstrate. Coinfusion of 2-deoxyglucose, a nondegradable hexose, in presence of excess pyruvate as sole substrate was without effects on residual ventricular pump function. When 1 mM lactate plus 5 mM glucose were the substrates, hypoxic heart function was also depressed, V (Ado + Ino) was relatively increased, and post-hypoxic recovery of pressure parameters was impaired. Similarly, the fatty acid substrates tested seemed to adversely affect cardiac performance during hypoxia. Extra pyruvate in presence of glucose induced a fall in hypoxic myocardial lactate and alpha-glycerophosphate contents while cellular citrate reached millimolar levels. Obviously, utilizable amounts of glucose were required for pyruvate stabilization of the high flow hypoxic heart. The beneficial effects of pyruvate appeared to depend on a functioning glycolysis; other effects seemed to include redox-related changes in energy state and/or purine nucleoside metabolism as well as a possible citrate buffering of intracellular Ca2+ load. PMID- 3086562 TI - Late onset of myoclonic epilepsy of Janz. AB - Myoclonic epilepsy of Janz is an essentially benign disorder with excellent response to valproic acid. The onset of myoclonic seizures in a patient at the age of 47 years, with normal mental status and a normal neurological examination, is reported. The electroencephalogram showed typical 3- to 5-Hz polyspike and wave complexes, some associated with myoclonic jerks but without loss of consciousness. The patient responded well to divalproex sodium, which controlled her seizures. A discussion of the condition and a review of the literature are included. PMID- 3086563 TI - Evaluation of particulate air samplers for airborne aflatoxin B1. AB - Five air samplers (Millipore, all-glass impinger, centrifugal, Andersen, and absorbent cotton) were evaluated for their ability to collect airborne grain particles contaminated with aflatoxin B1. Corn dust containing 100 micrograms aflatoxin B1/g was aerosolized within a containment system. Each device sampled 100 I air, thus exchanging the air in the chamber two times. Aflatoxin B1 was extracted from all sampling matrices and was detected and quantitated with thin layer chromatography and scanning fluorodensitometry. The highest efficiency was obtained with the Millipore sampler, while the efficiencies of the centrifugal and the cotton samplers were almost identical. Efficiency of an Andersen was less, with no toxin recovered from an all-glass impinger. Measurement of particle size was accomplished with the Andersen sampler. PMID- 3086564 TI - Kinetics of carbaryl and malathion in combination in the rat. AB - The disposition and metabolism of pesticides used in combination, especially carbaryl and malathion, is of considerable toxicological importance. Radioactivity was rapidly absorbed from the rat gastrointestinal tract (GIT) following the administration of 0.25 ml of 10 mg/kg [14C]carbaryl (0.80 microCi), 10/10 mg/kg [14C]carbaryl/malathion (0.80 microCi), 10 mg/kg [14C]malathion (1.03 microCi), or 10/10 mg/kg [14C]malathion/carbaryl (0.86 microCi). The. administration of carbaryl or malathion, individually and in combination, followed a two-phase elimination model. The presence of malathion decreased the rate constants of absorption and beta-phase elimination of [14C]carbaryl. In the mean time, the length of the distribution phase and the area under the curve of [14C]carbaryl were decreased by malathion administration. Although [14C]malathion's absorption half-life was unchanged in the presence of carbaryl, increases were noted in the length of the distribution phase, beta-phase elimination half-life, and area under the curve for malathion when administered simultaneously with carbaryl. Both combinations caused an increase in 14C activity to be deposited in the fat as compared to the respectively labeled pesticide. However, only malathion increased the concentration of [14C]carbaryl remaining in the GIT tissues after the administration of the combined pesticides. The subcellular distribution of the liver indicated that the highest activity was present in the cytosol. These pesticides and their combinations were excreted primarily by the kidney, followed by the lung and the intestinal route. Although there was no alteration in the metabolic pathways due to the combinations, an increase in malaoxon and malathion diacid concentration in urine was observed after the administration of [14C]malathion/carbaryl as compared to [14C]malathion. The results from this study revealed that the combination of these pesticides altered fundamental pharmacokinetic parameters, which may explain some of the toxicities associated with exposure to these chemicals in combination. PMID- 3086565 TI - Potentiation of aflatoxin B1 induced hepatotoxicity in male Wistar rats with ethanol pretreatment. AB - The interaction of ethanol and aflatoxin B1 (AFB1)-induced hepatotoxicity was studied in male Wistar rats using the activity of plasma GOT and GPT, liver triglyceride and histopathologic changes of liver necrosis as indices. Pretreatment of four oral doses of ethanol (4.0 g/kg BW each) at 48, 45, 24 and 21 hrs prior to AFB1 (0.5 to 2.0 mg/kg BW) single i.p. administration caused a significant increase in the activity of PGOT (6 folds) and PGPT (5 folds), liver triglycerides (2 folds) and severity of liver necrosis at 48 hrs after AFB1 administration. Ethanol pretreatment potentiated AFB1-induced hepatotoxicity by increasing MFO enzymes, aniline hydroxylase and p-nitroanisole-O-demethylase activity and lipid peroxidation, and decreasing in cytochrome b5, epoxide hydrolase activity and hepatic glutathione content. However, it did not cause any significant change in the activity of NADPH-cytochrome c reductase and glutathione-S-transferase and cytochrome P-450. These results suggest that potentiation of ethanol pretreatment on AFB1-induced hepatotoxicity may be due to an increase in the metabolic formation of AFB1-2, 3-oxide and subsequent binding to DNA. PMID- 3086566 TI - Cationized ferritin binding and internalization during in vitro aging of mouse embryonic fibroblasts. AB - The anionic surface sites of mouse embryo fibroblasts in primary culture, aging in vitro, have been studied using cationized ferritin (CF) as a marker. We have not observed significant differences between early and late cells with respect to CF binding; the labelling is uneven and patchy in both cases. Due to the increase of their surface area with the mitotic age, the total amount of negative charges, per cell, must however be much higher in the late passage cells. Virtually no differences in the rates of CF endocytosis via coated pits, with subsequent delivery to large vacuoles and lysosomes, have again been observed, but there was a cisternal formation from apposed plasma membranes in the late cells. New findings with regard to previous studies with CF concern the capping of the labelled surface components, followed by phagocytosis of the cap material, and the organization of the extracellular matrix in a rather regular network at the periphery of the cells. PMID- 3086567 TI - Effects of encainide on the inducibility of ventricular arrhythmia in normal anesthetized dogs. PMID- 3086568 TI - Bacteriocinlike killing action of a temperate bacteriophage phiBA1 of Bacillus aneurinolyticus. AB - A new temperate phage, phiBA1, was isolated from Bacillus aneurinolyticus, phiBA1 had an icosahedral head with a diameter of about 70 nm and a tail about 20 nm long and contained a circularly permuted, linear duplex DNA of about 38 x 106 daltons. This phage showed two activities: bacteriocin-like killing activity against five strains of B. aneurinolyticus and normal temperate phage activity against three other strains. phiBA1 killed sensitive cells by a single-hit process. After adsorption of phiBA1 to cells sensitive to killing, the content of intracellular ATP increased for the first 5 min and then gradually decreased. Phage DNA injected into the cell immediately after infection was degraded rapidly. Killing was also caused by heavily UV-irradiated phiBA1. Killing resistant mutants showed normal adsorption of phiBA1 and normal injection of the DNA with its instantaneous restriction. Our results indicate that the killing action of phiBA1 is different from the phenomenon of abortive infection and suggest that the killing might be caused by a proteinaceous component of phiBA1. PMID- 3086570 TI - Comparison of the costs and morbidity of percutaneous and open flank procedures. AB - A series of 47 percutaneous procedures for renal calculi was matched by description of calculi and previous flank exploration to 47 open flank procedures for comparison of relative morbidity and cost-efficiency. A retrospective analysis of paired data demonstrated that patients undergoing percutaneous procedures experienced significantly decreased duration of anesthesia, number of transfusions, postoperative disability, and duration and cost of hospitalization. These findings support the cost-effectiveness of the percutaneous approach to removal of renal calculi. PMID- 3086569 TI - Genetic control of serum neutralizing-antibody response to rabies vaccination and survival after a rabies challenge infection in mice. AB - Quantitative differences in serum neutralizing-antibody (SNAb) responses to rabies vaccination and survival after a rabies challenge infection between two inbred mice strains, C3H/J and C57BL/6J, were shown to be under genetic control. A 99% confidence limit calculated from the SNAb response titers of 14 C57BL/6J mice resulted in an upper limit for the SNAb response titer of C57BL/6J mice at 50.63. A SNAb titer less than or equal to 50.63 in response to rabies vaccination was assigned the phenotype of hyporesponder, and a SNAb titer greater than 50.63 in response to rabies vaccination was assigned the phenotype of hyperresponder in this study. The hyper-SNAb response to rabies vaccination and the higher frequency of survival after rabies challenge infection behave as Mendelian dominant alleles in F1 hybrids (C3H/J X C57BL/6J) and backcross (BC) (F1 [C3H/J X C57BL/6J] X C57BL/6J) progeny. Both a relatively hyper-SNAb response and a higher frequency of vaccine-inducible survival phenotypes occur in C3H/J mice. On the other hand, both the relatively hypo-SNAb response and a lower frequency of vaccine-inducible survival phenotypes behave as Mendelian recessive alleles and occur in C57BL/6J mice. C3H/J mice are H-2 Kk, and C57BL/6J mice are H-2 Kb. All three phenotypic traits (H-2 type, SNAb response, and survival after rabies challenge infection) segregate as independent (unlinked) monogenic traits in BC progeny (F1 [C3H/J X C57BL/6J] X C57BL/6J). The genetically controlled survival trait is inducible by rabies vaccination, but SNAb response is not a parameter that measures successful vaccine induction of preexposure protection from a rabies challenge infection in the BC progeny. The essential role of vaccination in developing preexposure protection in genetically responsive mice is confirmed, but indicates that in vitro measurements other than SNAb titers need to be developed to identify mice that have failed to achieve preexposure protection by rabies vaccination. This study confirms Lodmell's findings (D. L. Lodmell and B. Chesebro, J. Virol. 50:359-362, 1984; D. L. Lodmell, J. Exp. Med. 157:451-460, 1983) that susceptibility to rabies infection is genetically controlled in some mice strains. Additionally, this study indicates that conventional rabies vaccination even with more potent vaccines may not induce protection from infection in some genetically susceptible individuals. PMID- 3086571 TI - Schistosomiasis and renal transplantation. AB - Schistosomiasis was discovered in 4 recipients and 12 donors during evaluation for 67 consecutive live related renal transplants. All participants with schistosomiasis were treated with anti-schistosomal chemotherapy preoperatively. No complications were seen in the 4 recipients, including 2 with schistosomal induced calcifications of the bladder. One donor returned to an endemic area and became reinfected with slight progression of distal ureteral dilatation. Cystoscopy with biopsy is more sensitive in the detection of infection than ultrasonography, excretory urography or urinalysis but structural changes are assessed by excretory urography. Although schistosomiasis is not an absolute contraindication for renal transplantation, potential live kidney donors with proved anatomical changes in the urinary tract should be excluded. PMID- 3086572 TI - Bilateral pelvic lymphadenectomy and radical prostatectomy for clinical stage C prostatic cancer: role of adjuvant treatment for residual cancer and in disease progression. AB - A total of 101 patients with limited but unequivocal clinical stage C adenocarcinoma of the prostate underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy. At operation 49 patients had pathological stage C and 52 had stage D1 disease. Followup ranged from 0.5 to 17 years (mean 4.9 years). The 5 and 10-year observed survival rates for patients with stages C and D1 disease were similar to the expected survival. Sixteen patients had residual cancer postoperatively but only 2 had local progression: 1 had received no adjuvant therapy, and 1 had received diethylstilbestrol and radiation. None of the others, having received adjuvant radiation and/or orchiectomy, suffered local recurrence. Over-all, local progression occurred in 17 patients, only 4 of whom had received adjuvant treatment initially (diethylstilbestrol, 1 also received radiation). Local progression occurred in 13 of 47 patients (28 per cent) without adjuvant treatment. Thus, in all patients immediate adjuvant bilateral orchiectomy or radiation (except for 1 patient) prevented local progression. In patients with pathological stage D1 disease bilateral orchiectomy significantly reduced disease progression (p less than 0.0001). Therefore, limited clinical stage C adenocarcinoma of the prostate can be successfully treated surgically (with low morbidity) when supplemented with appropriate immediate adjuvant treatment. PMID- 3086573 TI - Hodgkin's disease of the prostate: a detailed case report. AB - Malignant lymphoma of the prostate is an unusual entity, and nonHodgkin's lymphoma constitutes most reported cases. We report a well documented case of Hodgkin's lymphoma, initially involving the gastrointestinal tract and spleen, which recurred in the prostate following initial remission with chemotherapy. Treatment with external beam radiotherapy resulted in a rapid complete response that has been sustained for 18 months. PMID- 3086574 TI - The effect of streptozotocin-induced diabetes on PGI2 synthesis by the rat bladder. AB - The effect of streptozotocin-induced diabetes mellitus on prostacyclin (PGI2) production by the urinary bladder in rats was investigated. Acute ketotic (two days duration) and non-ketonuric (seven days duration) diabetes had no effect on PGI2 production by the aorta or the bladder. "Chronic" untreated non-ketonuric (62 days duration) diabetes had a marked inhibitory effect on aortic PGI2 secretion which was not observed when rats were treated with insulin. Urinary bladders from animals with "chronic" untreated non-ketonuric diabetes were larger and heavier, and their walls were hypertrophic. The bladders from these latter animals produced more total PGI2, as well as more PGI2 per unit weight. Enhanced PGI2 production by bladders from animals with untreated non-ketonuric diabetes indicates that: 1) severity of the metabolic disturbance due to diabetes mellitus (ketosis) is not as important as the duration of diabetes as far as the induction of changes in PGI2 production is concerned; 2) distension and hypertrophy of the bladder and hyperosmolar urine are probably more potent stimulators of PGI2 production than diabetes is an inhibitor; 3) diabetes mellitus may have a variable effect on PGI2 secretion patterns in different tissues; 4) urinary excretion of PGI2 or its stable metabolite, 6-oxo-PGF1 alpha may not exclusively reflect PGI2 production by systemic vasculature and/or the kidneys; and 5) good control of diabetes prevents the bladder wall and PGI2 synthesis changes. PMID- 3086575 TI - A trial of prophylactic thiotepa or mitomycin C intravesical therapy in patients with recurrent or multiple superficial bladder cancers. AB - There were 40 consecutive patients with recurrent or multiple superficial stage Ta or T1 transitional cell cancer assigned randomly to receive prophylactic thiotepa or mitomycin C intravesical chemotherapy. Patients received 8 weekly instillations followed by 22 monthly treatments of either 60 mg. thiotepa or 40 mg. mitomycin C. Of 25 patients randomized to receive mitomycin C 4 had recurrence in a total of 337 patient-months (1.19 per 100 patient-months), while disease recurred in 1 of 15 patients randomized to receive thiotepa who were followed for a total of 220 patient-months (0.45 per 100 patient-months). No significant difference in recurrence rate was noted for either drug group (p equals 0.18). Toxicity requiring cessation of therapy was observed in 7 patients (28 per cent) on mitomycin C and none on thiotepa. PMID- 3086576 TI - Prevalence of Sarcocystis in wolves and white-tailed deer in Northeastern Minnesota. AB - The prevalence of Sarcocystis (Protozoa: Sarcocystidae) in white-tailed deer (Odocoileus virginianus) from northeastern Minnesota was determined by histologic examination of tongue samples. Seventy-nine of 100 deer were infected; infection was higher in yearlings and adults than in fawns. Sporocysts of Sarcocystis were found in 3% of 72 wolf (Canis lupus) scats. Three of four captive wolves fed muscle from a white-tailed deer naturally infected with Sarcocystis shed sporocysts 12-14 days later. PMID- 3086577 TI - Lead exposure in an "urban" peregrine falcon and its avian prey. AB - Necropsy of a 7-yr-resident peregrine falcon (Falco peregrinis) from Baltimore showed a Pseudomonas infection involving the pharynx as the immediate cause of death. Concentrations of lead in liver and kidney measured 0.74 and 1.40 ppm, respectively. A survey of lead exposure was performed on 40 urban rock doves (Columbia livia). Thirteen additional rock doves were collected from sites removed from lead contamination and served as controls. The mean concentration of lead in the blood of the urban rock doves was 0.96 ppm (range 0.29-17.0 ppm) compared to 0.05 ppm (0.01-0.07 ppm) for control birds. Ninety-eight percent (39/40) of the urban rock doves had elevated concentrations of lead in their blood, while 27% (11/40) had sublethal concentrations. None of the control birds had increased concentrations of lead in their blood. Concentrations of lead in liver and kidney of 13 urban rock doves were 3.48 ppm and 9.53 ppm, respectively, compared to concentrations of 0.43 ppm and 0.50 ppm for four control rock doves. From these data a mean total concentration of lead per rock dove was calculated at 4.60 ppm for urban birds and 0.33 ppm for control birds. PMID- 3086578 TI - Coexistence of Prader-Willi syndrome, congenital ectropion uveae with glaucoma, and factor XI deficiency. AB - A patient with Prader-Willi syndrome and unilateral congenital ectropion uveae with glaucoma was found to have factor XI deficiency and reduced levels of serum luteinizing hormone, follicle-stimulating hormone, and testosterone. Administration of gonadorelin (LH-RH) increased serum levels of luteinizing hormone and follicle-stimulating hormone, while clomiphene citrate had no effect, suggesting a primary hypothalamic defect. Patients with congenital ectropion uveae should be followed up for the development of both glaucoma and neural crest disorders. PMID- 3086579 TI - Converting patients from intravenous lidocaine to oral tocainide treatment. PMID- 3086581 TI - Leads from the MMWR. Plasmid-mediated tetracycline-resistant Neisseria gonorrhoeae--Georgia, Massachusetts, Oregon. PMID- 3086580 TI - Tocainide-induced granulomatous hepatitis. PMID- 3086582 TI - Elemental diet administered nasogastrically without starter regimens to patients with inflammatory bowel disease. AB - The present study questions the concept of routinely using 'starter regimens' at the outset of enteral feeding with chemically defined elemental diets. A hypertonic elemental diet with an osmolality of 630 mOsm/kg was administered by 24-hr nasogastric infusion to 12 patients with exacerbations of inflammatory bowel disease and to two patients with short bowel syndrome. Starter regimens were not used. Upper gastrointestinal symptoms of nausea, abdominal bloating, and colicky pain occurred transiently in only five of 14 patients. Stool frequency did not increase during full-strength feeding, and daily stool weights decreased significantly (p less than 0.01). These findings show that it is safe to administer undiluted hypertonic elemental diets by constant nasogastric infusion to patients with inflammatory bowel disease. Avoiding starter regimens leads to increased nutrient intake and improved nitrogen balance. PMID- 3086584 TI - An evaluation of total parenteral nutrition in the management of steroid dependent and steroid-resistant patients with Crohn's disease. AB - This study is an evaluation of short- and long-term benefits of total parenteral nutrition (TPN) in 20 patients with active Crohn's disease but without fistulae. TPN was done during 42 (14-80) days (median-range) after failure of medical therapy including patients with steroid-resistant (11 SR) or steroid-dependent (9 SD) active Crohn's disease. Efficacy of short-term TPN was demonstrated by nutritional repair and achievement of clinical remission in all but one patients. Follow-up was 28 (8-78) months in the 19 patients (10 SR, 9 SD) discharged improved after the end of TPN. At 1 yr, the cumulative recurrence rate was 26% (5/19). During the follow-up, three patients (2 SR, 1 SD) remained symptom-free, 13 (6 SR, 7 SD) had a partial remission defined as relapse controlled by medication, and only three patients (2 SR, 1 SD) had a relapse uncontrolled by medical therapy leading to surgery. Therefore in our selected population without fistula or abscess, after failure of medical therapy TPN was obviously an effective therapy which avoided surgery. Furthermore follow-up indicated that SD and SR were only transient events in the course of Crohn's disease patients. PMID- 3086583 TI - Bone and mineral status of patients beginning total parenteral nutrition. AB - Total parenteral nutrition (TPN) is commonly used to provide nutrition in the seriously ill. Osteomalacia has been described with long-term TPN and the administered solutions and/or vitamin D metabolites have been blamed for the occurrence of osteomalacia. These studies however were performed on patients on long-term TPN programs. We in contrast measured the serum calcium (Ca), ionized calcium (Ca2+), phosphate (Pi), bone GLA protein (BGP), alkaline phosphatase (ALK P), 25(OH)D, 1,25(OH)2D, the iPTH (carboxyl terminal) in 25 malnourished patients just beginning TPN therapy. The patients ranged from 25 to 80 yr of age and suffered from a variety of diseases. No patient had symptoms, recent fractures, or radiographic evidence of osteomalacia. The results of our study revealed significantly lower 25(OH)D (p less than 0.001), Pi (p less than 0.01), and Ca (p less than 0.01), but higher iPTH (p less than 0.002) values when compared to normals. BGP, 1,25(OH)2D and Ca2+ and ALK-P were not significantly different. We conclude that patients requiring TPN have low serum 25(OH)D values reflecting their nutritional status with a compensatory increase in PTH secretion to maintain their serum Ca2+ levels. The normal BGP levels may indicate depressed bone formation and skeletal resistance to PTH in the very ill patient. The cause of osteomalacia in these patients may therefore be multifactorial and not only related to the TPN infusions. PMID- 3086585 TI - Metabolic derangements in children requiring parenteral nutrition. AB - Intravenous alimentation is routinely used in many hospitalized pediatric patients, however, there are few reports of the nature and frequency of metabolic complications. In order to assess the frequency and nature of metabolic complications all children receiving parenteral nutrition from January 1, 1982 to December 31, 1982 were prospectively enrolled in the study. Data collection began with the institution of parenteral nutrition. Serum electrolytes, minerals, liver function tests, and renal function tests were followed weekly. A total of 201 patients received parenteral nutrition for 5378 days. Nutrition was delivered to 146 patients (4980 patient days) via a central line and 55 patients via a peripheral line (398 patient days). The sepsis rate was 3.7% in central lines used only for parenteral and 4.8% in multipurpose central lines. In general, complications were fewer in the patients supported peripherally. In patients supported centrally, hypoalbuminemia was the most commonly found abnormality followed by hypocalcemia, hypophosphatemia and hypomagnesemia, reflecting a malnourished state. One-third of the patients had abnormal liver function tests, and in half of those factors causing liver dysfunction other than parenteral nutrition were present. Abnormal renal function tests occurred in 10% of the patients. Thus, a high incidence of metabolic complications occurred in association with parenteral nutrition. Most were present during the initiation of parenteral nutrition, suggesting an abnormal metabolic state was present prior to the institution of parenteral nutrition. The frequency of low serum albumin and minerals is consistent with previous publications of the prevalence of malnutrition in hospitalized patients. PMID- 3086586 TI - Phenobarbital does not prevent total parenteral nutrition-associated cholestasis in noninfected neonates. AB - Cholestasis associated with total parenteral nutrition (TPN) is a serious complication of this therapy for which there is no known treatment other than beginning enteral feeds. Phenobarbital is commonly used in other cholestatic disease states, but its benefit in this syndrome has not been demonstrated. We conducted a retrospective review of phenobarbital use in neonates receiving concurrent TPN. Thirty-one noninfected neonates were studied. They were without evidence of intrinsic liver disease at the institution of exclusive TPN therapy. For the purposes of this study, TPN-associated cholestasis was defined as a serum bilirubin in excess of 3 mg/dl at postnatal age of 3 weeks or more. Fourteen of the study infants received phenobarbital therapy for neurologic indications. Sixty percent of the phenobarbital-treated infants developed TPN-associated cholestasis, as compared to 33% of the untreated patients. Phenobarbital therapy was not effective in preventing TPN-associated cholestasis. PMID- 3086587 TI - Hematologic disorders following prolonged use of intravenous fat emulsions in children. AB - Abnormalities in hematologic parameters, associated with prolonged utilization of intravenous fat emulsion (IVFE), were observed in seven children on long-term cyclic total parenteral nutrition (TPN). All patients were receiving IVFE (Intralipid 20%) 1 to 2 g/kg/24 hr as part of TPN, during 3 to 18 months. Recurrent thrombocytopenia occurred in all seven patients. Platelet lifespan, as measured with 111 Indium was reduced. Sea-blue histiocytes containing granulations and hemophagocytosis were seen on bone marrow smears. Scans taken after injection of autologous erythrocytes labeled with technetium-99 showed bone marrow sequestration of these cells. Taken together, this constellation of hematologic abnormalities suggests that long-term IVFE administration induces hyperactivation of the monocyte-macrophage system. PMID- 3086588 TI - Supplemental parenteral nutrition in cystic fibrosis. AB - The efficacy and safety of short-term supplemental peripheral hyperalimentation (PH) was evaluated in 15 hospitalized cystic fibrosis (CF) patients who exhibited varying degrees of pulmonary disease severity and nutritional impairment. An average of 1000 supplemental calories/day were administered intravenously for a 2 to 3-week period to patients being treated with parenteral antibiotics for exacerbation of their pulmonary disease. Eleven of 15 patients responded with a weight gain of greater than 2.0 kg and showed continued weight gain and stabilized pulmonary status for the 6- to 12-month follow-up period; two patients showed dramatic reversal of poor weight gain and growth following PH. Total calorie intake (oral + PH) equaled 141 +/- 40% of the recommended dietary allowances (RDA) in responders, with 45 +/- 12% RDA contributed by PH, in contrast to 68 +/- 20% of the RDA for total calories with 31 +/- 13% supplied using PH achieved in the nonresponders. Linoleic acid deficiency was documented in these patients (linoleic acid level as a percent of total fatty acid = 21.9% +/- 1.41 SEM vs 31.8% +/- 1.16 SEM in normal controls), and all seven patients achieved normalization of linoleic acid level after PH. Prior assessment of nutritional status (anthropometric measurements) or of severity of pulmonary disease (NIH clinical score) did not allow prediction of response to PH. No complications resulted from administration of PH to these hospitalized CF patients. PMID- 3086590 TI - Recommendations of nutrition support team promote cost containment. AB - Traditionally, Nutrition Support Teams (NST) have been employed in an advisory capacity to recommend the most beneficial type of total nutritional support. Frequently, this form of therapy is also the most economical, particularly when enteral nutrition can replace parenteral nutrition. In a retrospective study, we reviewed the files of 31 patients who had received total nutritional support and compared the nutritional therapy initiated by their attending physicians to the therapy recommended by the NST. Based on guidelines established by the NST, we evaluated patient records for appropriateness of therapy and potential monetary savings had the NST's recommendations been followed. In the majority of cases in which compliance with the NST's recommendations was not accepted, the NST had encouraged the use of enteral nutritional support rather than parenteral nutrition. In the 14 noncompliant cases (representing 280 days of nutritional support) the potential savings to these patients was estimated at $70,200 (more than $5,000 per patient). PMID- 3086589 TI - Total parenteral nutrition in very low birth weight infants with Travasol 10% blend C. AB - Ten very low birth weight (VLBW) infants (birth weight: 994 +/- 66 g, gestational age: 27 +/- 0.5 wk) requiring total parenteral nutrition (TPN) were studied in order to evaluate their metabolic response to the amino acid solution Travasol 10% blend C. These patients received the solution at a constant rate, providing 2.61 +/- 0.02 g/kg/day of amino acids and 76 +/- 1 kcal/kg/day. Plasma amino acids analysis was performed after 4.6 +/- 0.3 day of infusion and compared to values reported previously with Travasol blend B. The new solution (blend C) showed a significantly lower (p less than 0.001) glycinemia (485 +/- 24 vs 993 +/ 69 mumol/liter), methioninemia (39 +/- 2 vs 114 +/- 12 mumol/liter) and phenylalaninemia (67 +/- 3 vs 92 +/- 5 mumol/liter) related to the lower intake of these amino acids. Despite the provision of 47.5 mmol/liter of serine with blend C no changes in plasma level (182 +/- 15 vs 196 +/- 41 mumol/liter) were noted. The increased molar arginine/glycine ratio (blend C: 0.48 vs blend B 0.22) could have contributed to keep ammoniemia within normal levels (55.1 +/- 4.2 mumol/liter). Wide variations in insulin response (9.9 to 26.4 microU/ml) allowed for a correlation between its plasma concentration and those of sensitive amino acids, underlining its role in protein metabolism. Despite the immaturity of the study population no short-term metabolic imbalance has been encountered with the Travasol blend C solution. PMID- 3086592 TI - Total parenteral nutrition-associated metabolic acidosis. AB - To prevent acid-base disturbances, a patient receiving intravenous nutritional solutions must excrete the daily metabolic production of acid. These hydrogen ions are generated from external (infused) sources and internal metabolic processes. Patients with normal respiratory and renal organ function are capable of excreting these volatile and nonvolatile acids, respectively, and maintaining acid-base balance. However, increased renal or gastrointestinal loss of bicarbonate, diminished renal excretion of acid, or increased acid production may all result in a metabolic acidosis. This article reviews the mechanisms of hydrogen ion production associated with total parenteral nutrition and the variety of disease states leading to development of a metabolic acidosis. PMID- 3086591 TI - Vitamin E status in patients on parenteral nutrition receiving Intralipid. AB - Low vitamin E levels have been found to be a frequent side effect in patients on total parenteral nutrition (TPN). In the present study, the vitamin E content of fat emulsions (Intralipid) was measured and the influence of the intravenously administered lipid emulsion on plasma vitamin E levels was investigated. The majority of vitamin E was provided in the beta + gamma-tocopherol fractions (68.7% of total tocopherol). Vitamin E levels in patients were significantly lower (p less than 0.05) as compared to age- and sex-matched normal controls. Although sufficient amounts of vitamin E (16.9 +/- 0.8 IU daily) were infused, according to RDA requirements, E-plasma levels decreased even further during the course of TPN. It was concluded that high amounts of biologically less active tocopherol isomers are not sufficient to maintain vitamin E plasma levels. Supplemental sources of alpha-tocopherol are needed and more attention should be paid to the different tocopherol isomers in the quantitation of the daily allowances of vitamin E. PMID- 3086593 TI - Interaction of oral phenytoin with enteral feedings. AB - A 48-yr-old man with squamous cell carcinoma of the lung, hypercalcemia, and brain metastases with seizures was treated with phenytoin. Constant nasogastric infusion with Osmolyte was begun for hydration and nutritional status, necessitating an increase in his phenytoin dosage. Adequate seizure control and phenytoin levels were obtained on this adjusted regimen. However, on the 16th hospital day, the patient pulled out his nasogastric tube and received two doses of phenytoin without Osmolyte. The patient became lethargic, and his phenytoin level was 53 micrograms/ml. The patient was placed on bolus nasogastric feedings and a lower dose of phenytoin administered between feedings. Adequate seizure control and appropriate phenytoin levels were obtained with no further problems. The recommended management of the phenytoin-enteral feeding interaction is to flush and clamp the nasogastric tube for 2 hr before and 2 hr after the phenytoin dose. PMID- 3086594 TI - [General anesthesia for a patient with IHSS (idiopathic hypertrophic subaortic stenosis) and von Recklinghausen's disease]. PMID- 3086595 TI - [The role of radiotherapy in the treatment of non-Hodgkin's lymphoma of the thyroid]. AB - Retrospective analysis was made of 30 cases of non-Hodgkin's lymphoma treated from 1967 through 1983 at the Department of Radiology, Osaka University Hospital, according to the Ann Arbor staging classification modified by us. Overall five year survival and five-year relapse-free survival were 62% and 60%, respectively, with one out of 9 cases treated since 1979 being lost due to relapse. In cases with disease localized in the thyroid and neck nodes (Stage IIE-a, by modified classification), five-year survival of 74% was obtained, whereas in those with the lesion extending to the mediastinum (IIE-b) or axillae (IIE-c), the survival pattern was similar to that with Stage II and IV. Complete local control was obtained in all cases by radiotherapy. PMID- 3086596 TI - [Tuberculosis in patients with malignant neoplasms]. AB - Out of 810 patients autopsied at our institute between 1972 and 1985, tuberculosis was demonstrated in 12 (1.5%), all between 40 and 80 years of age, regardless of cancer type. Of 4,272 patients who underwent surgery for malignant neoplasms, 481 were examined for M. tuberculosis by culture in different specimens. All of eight positive cases were with sputum or bronchial mucus specimens, regardless of the site of primary cancer. Tuberculosis complicating malignant thymoma or Hodgkin's disease was found to be generalized and severe. Remarkable growth of elongated bacteria was observed in host macrophages in these immunodeficient patients, suggesting their altered intracellular environment. These findings warrant special attention to tuberculosis in hospital care of cancer patients, who are often immunodeficient. PMID- 3086597 TI - [Prospective adjuvant chemotherapy, with mitomycin C plus long-term carmofur in colorectal cancer]. AB - A prospective randomized controlled trial of adjuvant chemotherapy for colorectal cancer was performed in 41 institutions in the Tokai district. In the study, postoperative administration of Mitomycin C (MMC) followed by carmofur (HCFU) for more than three months (arm B) was compared to MMC alone (arm A). Of 173 patients subjected to curative resection (arm A = 80, arm B = 93) for colorectal cancer, 148 including 69 from arm A and 79 from arm B were evaluable. Before clinical evaluation of the effectiveness the background factors were analyzed by the chi square test and U-statics. There were no differences between them. At four years after surgery Kaplan-Meire's life table showed that the disease free survival of arm B was superior to that of arm A, but this difference was not statistically significant (generalized Wilcoxon test: P less than 0.10). However, the survival in arm B was significantly prolonged as compared with that in arm A (P less than 0.05). Side effects such as leukopenia and gastrointestinal distress caused by administration of MMC and pollakisuria and gastrointestinal distress caused by administration of HCFU were observed in approximately 35% of the patients. They were all slight or moderate and reversible. PMID- 3086598 TI - [Results of stage III carcinoma of the uterine cervix treated by conformation radiotherapy]. AB - From 1967 through 1982, 206 patients with stage III carcinoma of the uterine cervix were treated by conformation radiotherapy. In the first half of the period (group A), external irradiation alone was used, while in the second half (group B), intracavitary irradiation with a low dose-rate was applied in combination with external irradiation. The two-year local control rate was 56.9% in group A and 81.5% in group B. With the combined use of intracavitary irradiation, the five-year actuarial survival rate was also improved from 45.5% in group A to 59.7% in group B. At the same time, the frequency of late injury of the rectum, sigmoid colon and the urinary bladder was also decreased with the use of small sources. It can be concluded that the combined application of intracavitary irradiation and external irradiation is important to improve the treatment results of stage III carcinoma of the uterine cervix. PMID- 3086599 TI - [Megaloblastic anemia due to folate deficiency--including a case complicated by intravenous hyperalimentation or tube feeding]. PMID- 3086600 TI - [Recent progress in fibrinolytic mechanism]. PMID- 3086601 TI - [A case of meningitis infected with listeria monocytogenes type 3b]. PMID- 3086602 TI - [Analysis of 5-year survival in radiotherapy alone in esophageal carcinoma]. PMID- 3086604 TI - Monoclonal gammopathy in beta thalassaemia. AB - A rare instance of IgG-kappa monoclonal gammopathy in a patient with beta thalassaemia trait is reported. The patient had a smoldering multiple myeloma with no apparent clinical symptoms pertaining to the disease and was a non responder to conventional Melphalan and prednisolone therapy. Beta-thalassaemia trait was detected while investigating him for anaemia. A state of altered immunological reactivity, chronic infections and associated biliary tract disease are some of the pathogenetic mechanisms suggested. However in this patient none of these were operative. PMID- 3086603 TI - [Evaluation of In-111-platelet scintigraphy in diagnosis of intracardiac thrombus]. PMID- 3086605 TI - Intravascular bronchiolo-alveolar tumor (IVBAT). Case report with the immunological analysis. AB - A case of intravascular bronchiolo-alveolar tumor, a rare lung neoplasm which is often found among women, is reported. Our ultrastructural findings and existence of factor VIII-related antigen support the hypothesis of vascular origin. The relationship between IVBAT and epithelioid hemangioendothelioma is discussed. We also examined whether immunological abnormalities existed in our patient, because tuberculin test gave negative result in many cases reported previously and our case. No specific immunological change was found except for negative tuberculin test. PMID- 3086606 TI - Sex difference in the effect of aspirin on intracellular Ca2+ mobilization and thromboxane A2 production in rat platelets. AB - The intracellular Ca2+ mobilization in thrombin-stimulated platelets was greater in male rats than in female rats. Thromboxane (TX) B2 production in male platelets was greater than that in female platelets. Aspirin suppressed Ca2+ mobilization in rat platelets, but the inhibitory effect of aspirin was more efficient in males than that in females. Aspirin inhibited TXB2 production, and this inhibitory effect of aspirin was stronger in male platelets than in female platelets. Castration decreased Ca2+ mobilization and TXB2 production and weakened the effect of aspirin on them. It is suggested that the sex difference in the antiplatelet effect of aspirin results from the difference in the inhibition of Ca2+ mobilization via the inhibition of TXA2 production in thrombin stimulated rat platelets. PMID- 3086607 TI - Bovine myoglobin: its purification and detection by the antiserum. PMID- 3086608 TI - Suppression and recovery of immunologic function after bone marrow transplantation. AB - Infections are common causes of death in patients undergoing bone marrow transplantation for aplastic anemia or leukemia. A better understanding of the immunologic recovery following marrow grafting may lead to clinical trials of which the goals are to improve immunologic reactivity and to decrease infection. PMID- 3086609 TI - [Analysis of pulmonary tuberculomas diagnosed by exploratory excision]. PMID- 3086610 TI - [Paradoxical effect of nitroglycerin in total coronary spasm]. PMID- 3086611 TI - [Dynamics of pituitary gonadotropin and sex hormone levels in men with myocardial infarction during rehabilitation]. AB - Blood levels of pituitary gonadotrophins: the follicle-stimulating hormone (FSH) and the luteinizing hormone (LH), and sex steroids: testosterone (T) and estradiol (E), were measured repeatedly on days 17, 30 and 60, and within 3.5 and 6 months after the onset of myocardial infarction in 60 male patients between 32 and 55 years of age. Stable LH, FSH, T and E levels of the first two months were succeeded with a significant decrease in T values as well as a simultaneous FSH rise, i.e. a combination of normo- and hypergonadotrophic hypogonadism, in men of 50-55 years. A complex process of readaptation to preinfarction stereotypes of situations arising at home and at work 2 or 3 months after the attack is believed to be one of the causes underlying this pituitary-sexual response. PMID- 3086613 TI - [Comparative evaluation of the effectiveness of parenteral feeding using various amino acid preparations in patients with acute pancreatitis]. PMID- 3086614 TI - [Effect of alvesin on the blood coagulation system in patients with stomach cancer]. PMID- 3086612 TI - Cardiopulmonary effects of cuprophane-activated plasma in the swine. AB - Hemodialysis with cuprophane membrane is associated with complement activation and the formation of anaphylatoxins. Frequently, it is also complicated by various adverse reactions which include hypoxemia and hemodynamic changes. This study examined the cardiopulmonary effects of cuprophane membrane on experimental animals. To support the hypothesis that these effects were mediated by complement activation products, the effects of zymosan-activated plasma and C5adesArg challenge on the same variables were compared. We showed that intravenous infusion of autologous cuprophane-activated plasma into swine produced severe pulmonary hypertension, hypoxemia and leukopenia. In addition, mean systemic arterial pressure fluctuated and cardiac output fell. Infusion of zymosan activated plasma produced similar results, suggesting that complement activation products are responsible for these alterations. Similar responses to porcine C5adesArg infusion suggested further that this polypeptide was the mediator. When swine were subjected to extracorporeal circulation using cuprophane membrane but without dialysis, acute pulmonary hypertension was seen preceding the onset of significant leukopenia. These data suggest that blood contact with cuprophane membrane produces both pulmonary and systemic hemodynamic changes, which are mediated by complement activation products. Furthermore, these products and/or other humoral factors, but not leukoagglutination, cause the pulmonary hypertension. PMID- 3086615 TI - [Intensive therapy of the complications of blood transfusion]. PMID- 3086616 TI - [Errors and hazards in the surgery of esophageal diverticula]. PMID- 3086617 TI - [Enteral tube feeding after emergency operations on the abdominal organs]. PMID- 3086618 TI - [Keratoplasty for severe lagophthalmic keratitis in patients with long-term artificial respiration]. AB - The authors report on 2 patients who developed dense opacities of the thinned cornea during long-term unconsciousness under intensive care, due to insufficient care of the cornea in the case of lagophthalmic keratitis. Although the keratoplasty performed was finally successful, postoperative treatment was very difficult, because the very thin host cornea made re-suturing necessary. The authors recommend using a donor graft 0.2 to 0.3 mm larger in such cases. In order to prevent a keratitis with subsequent corneal opacities. It is very important to instruct the nursing staff to take care to apply eye ointments regularly in unconscious patients with lagophthalmus. PMID- 3086621 TI - [Acute renal insufficiency complicating the course of salmonellosis]. PMID- 3086620 TI - [Fulminating course of IgG plasmacytoma at a young age]. AB - The case of a 27 year old patient with IgG-lambda-myeloma is reported. Examination revealed hypercalcemia and acute renal failure. The patient died of heart failure two days after diagnosis. Autopsy revealed an extensive calcification of the inner organs, in particular the heart. PMID- 3086622 TI - [Solcoseryl in the complex treatment of acute pneumonia]. PMID- 3086623 TI - Plasma lipids, lipoproteins and apoproteins B and A-I before and after a 24 h endurance race in cross-country skiers. PMID- 3086619 TI - Intravenous fibrinolytic therapy of acute myocardial infarction: new perspectives from plasminogen activators? AB - The early treatment of acute myocardial infarction has changed rapidly in recent years. Given the fact that an occlusive coronary thrombus can be found in most infarct patients within 4 h after clinical symptoms, the idea of instituting medical or mechanical recanalization of the occluded vessel is intriguing. However, invasive measures are time consuming, expensive and not freely available to a great number of patients. Thus, only i.v. fibrinolytic therapy of acute myocardial infarction will gain wider application in the near future. Several concepts have been worked out, one of which uses a high-dosage streptokinase or urokinase regimen. A different therapeutic alternative has been made possible by the development of selective fibrinolytic substances, such as the tissue-type plasminogen activator (t-PA) or the anisoylated plasminogen-streptokinase activator complex (APSAC). Preliminary clinical data have shown that the coronary artery patency rate achieved after i.v. administration of t-PA or APSAC is higher than that after conventional treatment with streptokinase or urokinase. The incidence of severe bleeding complications is low and comparable in these studies. However, until myocardial salvage has been demonstrated with early i.v. fibrinolytic therapy in acute myocardial infarction in a placebo-controlled randomized trial, this therapeutic concept will still be unsettled. PMID- 3086624 TI - Refractory hypoglycemia in a truck driver. PMID- 3086625 TI - Measurement of oxygen tension in the ischemic myocardium using encased polargraphic oxygen electrodes. AB - The ability to continuously monitor the delicate balance between blood flow and oxygen consumption would be a great asset in the study of myocardial ischemia. The present study was performed, in anesthetized dogs, to validate the use of encased polargraphic oxygen electrodes in the study of myocardial ischemia. Polargraphic oxygen electrodes were placed in the area to be rendered ischemic at fixed tissue depths of 3 mm (epicardium) and 9 mm (endocardium). Endocardial and epicardial oxygen tensions as well as the ratio of endocardial to epicardial oxygen tension and left circumflex coronary flow were monitored. Ischemia was induced by decreasing left circumflex coronary flow by 50%. Upon completion of a 20-min poststenotic period, endocardial pO2, endocardial/epicardial ratio, and coronary flow were significantly decreased (59 +/- 7, 52 +/- 7, and 55 +/- 4%, respectively) whereas epicardial pO2 was slightly decreased. Nitroglycerin (10 micrograms/kg, i.v.) markedly increased endocardial pO2 and endocardial/epicardial ratio above poststenotic control (13 +/- 5 mmHg and 64 +/- 10%, respectively) whereas epicardial pO2 was not significantly decreased. The increases in endocardial pO2 occurred at a point where coronary flow and mean arterial pressure were not significantly changed. Conversely, dipyridamole (125 micrograms/kg, i.v.) significantly increased coronary flow (26 +/- 2 ml/min/100 g) although it did not appreciably alter endocardial or epicardial pO2. It is concluded that encased polargraphic oxygen electrodes provide a quantitative method for determination of oxygen tension in the ischemic myocardium. PMID- 3086626 TI - A minimally invasive technique for the study of intravascular platelet aggregation in anesthetized rats. AB - A method for monitoring platelet aggregation in vivo in the rat is described, using platelets labeled with indium3+ oxine and recording the increase in radioactivity count in the lung after injection of adenosine diphosphate and collagen. The effects of adenosine diphosphate and collagen are reproducible between animals. 5-Hydroxytryptamine creatine sulfate, which is inactive on rat platelets in vitro, causes aggregation in vivo, and adrenaline, which is proaggregatory in vitro inhibits adenosine diphosphate-induced aggregation in vivo. Female rats are relatively insensitive to the aggregating agents, particularly during proestrus, although when platelets from proestrus females were injected into male rats, their sensitivity was increased. Platelets from male rats injected into female rats in proestrus have low sensitivity. PMID- 3086628 TI - Enhanced polyploidy by glutaraldehyde in cultured HL60 leukemic cells. AB - Glutaraldehyde 10(-4) M weakened cell proliferation of HL60 cultured cells and enhanced the appearance of giant polyploid cells, up to 32.5% after 6 days. The size and structure of these cells, the quantitative changes in their DNA content with respect to diploid ones demonstrate their polyploid nature, which may be corrected by the occurrence of pluripolar mitoses. However the slowing down of cell proliferation is not enough to orient the cells towards differentiation. Maturation of polyploid cells may be stimulated by retinoic acid and dexamethasone as for diploid ones. Several possible mechanisms of polyploidy are discussed. Except the possibility that the cells may directly fuse, the mechanisms which are considered, may involve a preprophase inhibition, a mitotic arrest at metaphase or a reduction of asters which may result in a defect in cytokinesis, the latter followed by secondary fusion of nuclei. PMID- 3086627 TI - Prostaglandin synthetase inhibition by alkaloids of Heimia salicifolia. AB - Two alkaloids from Heimia salicifolia, cryogenine and nesodine, were respectively 2.48 and 2.24 times as potent as aspirin as inhibitors of prostaglandin synthetase prepared from bovine seminal vesicles. Reference compounds, indomethacin and phenylbutazone, were respectively 2800 and 8.75 times as potent while a synthetic analogue of cryogenine, JB-1-0, was 0.656 times the potency of aspirin. This activity may help to explain the traditional medicine use of H. salicifolia in the Americas. PMID- 3086629 TI - Expression of Tac antigen on human immature B-cell lineage leukemic cells. AB - Expression of interleukin 2 (IL-2) receptor (Tac antigen) on leukemic cells from 4 patients with acute lymphocytic leukemia (ALL) and 3 patients with blastic crisis of chronic myelogenous leukemia (CML-BC) was examined. Cells from 6 out of 7 patients did not carry immunoglobulins on their surfaces, but reacted with monoclonal antibodies (mAb) detecting B-cell related antigens such as B1, OKB2 and Leu12. Cells from two cases expressed Tac antigen immediately after cell separation. Phorbol 12-myristate 13-acetate (PMA) could induce Tac antigen in all cases. SDS-PAGE analysis of immunoprecipitates by anti-Tac mAb demonstrated that the molecular weight of Tac antigen on most of the leukemic cells was similar to that of Tac antigen present on Con A-stimulated normal lymphocytes. These leukemic cells poorly responded to exogenous recombinant IL-2. These findings suggest that IL-2 may interact with the immature and mature B cells, and play an important role in the differentiation of B lymphocytes. PMID- 3086630 TI - Long-term care. PMID- 3086631 TI - Functional compartmentation of intracellular magnesium. AB - Due to the distribution of Mg2+-binding ligands, such as DNA, RNA, or Mg2+ binding proteins, e.g. within the intermembranous space of mitochondria, intracellular magnesium is compartmentalized. Furthermore, cytosolic free Mg2+ is enriched at charged surfaces. Thus, the exact concentration of free intracellular Mg2+ can only be ascertained for a small volume element. Compartmentation of intracellular Mg2+ can also be determined by flux measurements with 28Mg2+. In different cell types, cellular Mg2+ is exchanged with different velocities, and, in some cell types, rapidly and slowly or non-exchangeable compartments are detectable. Cells can be Mg2+-depleted gradually by incubation with A23187 and EDTA. In cells which are Mg2+-depleted gradually, the Mg2+-dependent metabolic functions are inhibited in the following sequence: glycolysis, RNA, DNA synthesis, respiration, protein synthesis, protein synthesis appears to be the most sensitive function affected. PMID- 3086632 TI - Peripheral T-cell lymphomas: histologic, immunohistologic, and clinical characterization. AB - A review of 40 cases of peripheral T-cell lymphoma identified at our institution between March 1983 and December 1985 revealed a clinically, histologically, and immunologically diverse group of neoplasms that were difficult to classify by conventional histomorphologic criteria for non-Hodgkin's lymphomas. These lymphomas were frequently extranodal at the time of initial manifestation (52%), and their clinical aggressiveness correlated with three major histologic categories--small lymphocytic, diffuse mixed, and large cell. Of the 40 lymphomas, 18 exhibited distinctive histologic features that allowed assignment of these cases into one of four subgroups: (1) angioimmunoblastic lymphadenopathy, (2) lymphomatoid granulomatosis, (3) Hodgkin's-like disease, and (4) Lennert's lymphoma (lymphoepithelioid lymphoma). Study of all our cases that fulfilled the morphologic criteria for lymphomatoid granulomatosis or angioimmunoblastic lymphadenopathy by using immunologic methods for identification of B-cell and T-cell antigens has shown these neoplasms to be peripheral T-cell lymphomas. Therefore, we now consider these earlier proposed entities to be distinct histologic variants of peripheral T-cell lymphoma. PMID- 3086633 TI - Management of recurrent rectal cancer. AB - In an effort to treat the difficult problem of recurrent rectal cancer more successfully, we embarked on an aggressive therapeutic course involving a combination of field irradiation, surgical debulking, and intraoperative radiation therapy. On the basis of our study of 24 patients treated with this regimen, we estimated the local effectiveness to be as high as 85%. Prolonged survival was achieved in 67% of our patients. PMID- 3086634 TI - Three-dimensional computed tomographic scanning and major surgical reconstruction of the head and neck. AB - The major advantage of three-dimensional computed tomographic imaging is the ability to obtain accurate anatomic measurements of distance, area, and volume. This accuracy is possible because the three-dimensional relationships of soft tissue and skeleton are retained. This feature is particularly useful in reconstruction of the upper facial skeleton, where standard roentgenograms and computed tomographic scans are of limited value. Computer-interactive surgical procedures have been used for correction of congenital deformities and for removal of orbital neurofibromas and subsequent reconstruction. Because three dimensional imaging is expensive and exposes the patient to high levels of irradiation, this approach is recommended only when a specific indication exists and when it can contribute to problem solving. PMID- 3086635 TI - Do immature T cells accumulate in advanced age? AB - The hypothesis that decreased T cell function in the elderly involves an increased number of less differentiated T cells was examined. Three markers known to change during thymocyte development were analyzed; ratio of adenosine deaminase (ADA) to purine nucleoside phosphorylase (PNP), lactate dehydrogenase (LD) H/M subunit ratios and the T cell associated antigens, T3, T4, T8 and T10. Cells tested were from 10 old (greater than 75 years) and 10 young (less than 35 years) persons with equal numbers of males and females in each group. Before analysis, cells were purified into three groups; unfractionated, and monocyte depleted T cell and B cell enriched populations. Results for ADA/PNP ratios showed no significant differences between old and young in any of the fractions analyzed. H/M ratios however, were significantly reduced in all three fractions from old donors when compared with young. Surface marker distribution pattern as illustrated by the T3 - (T4 + T8) difference was lower in samples from old donors but not significantly so. There was a very significant reduction in percent cells positive for T3 in all three fractions from old persons. Although some of the changes seen in these markers could be due to a failure of normal differentiation, they could also be caused by the general phenomenon of altered gene expression known to occur with advanced age in a variety of non-lymphoid cells. The absence of any difference in the ADA/PNP ratio suggests that T cell dysfunction in the elderly may not be due to increased numbers of less differentiated cells as a result of thymic involution. PMID- 3086636 TI - Decline, with age, in the proportion of mouse T cells that express IL-2 receptors after mitogen stimulation. AB - Receptors for IL-2 can be demonstrated on the majority of mouse splenic T cells within 48 h after stimulation with Concanavalin A. We show here that aging leads to a decline in the frequency of cells able to generate detectable levels of IL-2 receptor, as measured by cytofluorimetry using antibodies to the receptor. The age-associated deficit cannot be overcome either by increasing the mitogen dose, or by supplementing the cultures with exogenous IL-2. At least a part of the decline, with age, in T cell-mediated immunity may represent an inability of individual T cells to produce sufficient IL-2 receptor to enable them to reach the IL-2 dependent phases of their first cell cycle. PMID- 3086637 TI - Mass spectrometer system for long-term continuous measurements of v.O2 and v.CO2 during artificial ventilation. PMID- 3086638 TI - Medicaid and non-Medicaid case mix differences in Colorado nursing homes. AB - Profiles of case mix and related variables were compared for 1,064 Medicaid and 459 non-Medicaid residents of 65 freestanding nursing homes in Colorado in 1980. The results point to substantial case-mix differences, with Medicaid residents typically characterized by fewer and less intense long-term care problems as well as greater independence in functioning (ADLs). Policy impacts of these findings in Colorado have included a legislatively mandated home and community-based care program as well as a more stringent preadmission certification program for Medicaid clients. The method of comparing Medicaid and non-Medicaid case mix in nursing homes appears to have policy relevance for other states as well. Research implications in the areas of measuring severity of long-term care problems and measuring residents' functional abilities apart from services received are also suggested. PMID- 3086639 TI - Do interns and residents order more tests than attending staff? Results of a house staff strike. AB - Between October 30 and November 5, 1980, the Professional Association of Interns and Residents of Ontario called a strike of house staff in Ontario's teaching hospitals. The authors obtained data concerning utilization of laboratory tests and radiology procedures during that period and for the same days 2 weeks before and after the strike. During the strike period, the number of tests performed per patient day decreased by only 8.3%. After accounting for proportional changes in emergency and nonemergency admissions, there was no significant change in the number of tests or relative value units performed per patient day as a result of the strike. These results suggest that the volume of tests performed in teaching hospitals is more likely related to the case mix and severity of illness of patients admitted to these institutions than to a pure "teaching effect." PMID- 3086640 TI - Determinants of state variations in home health utilization and expenditures under Medicare. AB - Of the key federal programs that finance in-home services to the elderly, the Medicare program represents the largest and fastest growing. Although Medicare is a federal program, utilization and expenditures for home care vary widely across the states. Building on the work of Feldstein, Scanlon, and others, theory and data are presented that attempt to illuminate reasons why such variations exist. Using program data by state for 1982, nearly three fourths of the variation in home health utilization (R2 = 0.72) is explained by seven state characteristics. About three fifths of the variation in expenditures (R2 = 0.61) is accounted for by six state factors. Of most explanatory importance are home health agency (HHA) supply, need levels, presence of alternative sources of care, sources of referrals, and state resources. The results suggest the need to give more analytic attention to the impact of the market share of proprietary HHAs in explaining expenditure variations and the effects of total supply on utilization and spending. PMID- 3086641 TI - [Worsening of pulmonary respiratory function after the administration of lithium carbonate]. PMID- 3086642 TI - [Usefulness of the effective thyroxine and thyrotropin index in the evaluation of thyroid function in critical patients]. PMID- 3086643 TI - Influence of cianidanol on specific and non-specific immune mechanisms. AB - The influence of Cianidanol (Ci), a cytoprotective radical scavenger, on peripheral blood mononuclear cells (PBMC) was assessed with respect to its immunomodulatory function. In previous studies performed in our laboratory, a bidirectional influence of Ci on the immune response was observed, depending on its concentration. In order to elucidate this effect, the influence of Ci on macrophage (M phi) and B-cell function was investigated. A marked dose-dependent suppression of M phi phagocytosis by Ci could be detected. Furthermore, PGE2 synthesis of non-activated and PHA-activated PBMC was inhibited in the presence of Ci. This effect was shown to be due to an inhibition of M phi cyclooxygenase. It was also demonstrated that neither spontaneous nor Staphylococcus aureus Cowan I induced proliferation of highly purified B-cells was enhanced by Ci. Similar results were obtained by measuring the influence of Ci on immunoglobulin secretion of purified B-cells, exposed to Klebsiella membrane preparations. From these data it can be concluded that the previously described enhancing effect of Ci on immunoglobulin secretion is probably T-cell mediated. PMID- 3086644 TI - [Prognosis of viral hepatitis]. PMID- 3086645 TI - [Endoscopic manometry of Oddi's sphincter]. PMID- 3086646 TI - Follicle-stimulating hormone secretion in monosodium glutamate-lesioned rats: response to unilateral gonadectomy or porcine follicular fluid (inhibin). AB - The purpose of this study is to determine the acute response of pituitary FSH and LH release to unilateral gonadectomy in the MSG-treated rat, and to determine whether pFF (inhibin) can act effectively on pituitary FSH secretion in the MSG lesioned rat. MSG (4 mg/kg B.W.) or saline was injected subcutaneously on postnatal days 2, 4, 6, 8, and 10 to male and female littermates which were used in the experiments after postnatal day 60. In the first experiment male and female littermates were bilaterally gonadectomized and bled serially for the next 72 h. At 0 h plasma FSH concentrations in MSG-treated rats were lower (p less than 0.05) than those in saline-treated controls, and for the 72 h immediately following bilateral gonadectomy FSH levels increased parallel to those of the controls, but after a significant delay. In the second experiment, MSG-treated male and female littermates were injected with 0.5 ml of pFF at several intervals following bilateral gonadectomy and decapitated 6 hours later. Injection of pFF significantly suppressed circulating FSH titers in all groups without affecting LH levels. In a third experiment, rats were unilaterally gonadectomized and blood samples were obtained at various intervals for 48 h. Following unilateral gonadectomy there was a significant transient increase in FSH levels in male or female MSG-treated rats as compared to their 0 h values; however, the absolute levels attained were barely equal to the basal concentrations observed in the saline-treated control rats. The conclusions from these data are: insufficient FSH secretion in response to unilateral gonadectomy may be responsible for the lack of compensatory gonadal hypertrophy in MSG-lesioned rats, pituitary response to inhibin is apparently unaltered by MSG toxicity, and the MSG-lesioned rat is a useful model to study the differential control mechanisms of FSH and LH secretion. PMID- 3086647 TI - Modification of hepatic folate metabolism in rats fed excess retinol. AB - Feeding rats a diet containing 1000 IU of retinol/g diet enhances the folate dependent oxidation to CO2 of formate and histidine. The activity of hepatic methylenetetrahydrofolate reductase, which plays a critical role in the regulation of liver folate metabolism, is suppressed in these animals, resulting in decreased 5-methyltetrahydrofolate synthesis. This ensures a greater concentration of hepatic tetrahydrofolate, the coenzyme on which formate and histidine oxidation depend, but also compromises the level of S adenosylmethionine in the liver. PMID- 3086648 TI - Effect of praseodymium chloride on liver microsomal enzymes of rats. AB - A single i.v. dose (5 mg/kg) of a light lanthanon, praseodymium, prolonged the duration of hexobarbital-induced sleep and zoxazolamine-induced paralysis, as well as it modified pharmacokinetic parameters of hexobarbital and zoxazolamine, in rats. Half-lives (t1/2) and area under the curve (AUC) were increased, while elimination coefficient (beta) and clearance (Cl) were decreased. However, in daily doses of 1 mg/kg i.p. for 15 days, praseodymium did not alter pharmacological effects and pharmacokinetic parameters. The in vitro hydroxylation of hexobarbital and zoxazolamine by liver microsomes was inhibited when the animals were treated previously with a single i.v. dose (5 mg/kg) of praseodymium chloride. In these animals, the amount of cytochromes P-450 and b5 were reduced significantly, whereas that of NADPH-cytochrome c reductase remained unchanged. The pretreatment of animals with phenobarbital normalized the microsomal enzyme impairment caused by praseodymium. PMID- 3086649 TI - A re-interpretation of lipoxygenase-dependent insulin release: which metabolites of arachidonic acid, or none? AB - There are considerable data implicating a pancreatic islet 12-lipoxy-genase in glucose-induced insulin secretion. This enzyme traditionally is conceived as converting unesterified arachidonic acid to "free" hydroperoxyeicosatetraenoic acid and metabolites thereof. However, studies employing the provision of exogenous metabolites of arachidonic acid to islet tissue fail to identify convincingly the mediator of insulin release. It is proposed that the islet lipoxygenase directly peroxidizes unsaturated fatty acids esterified within membrane phospholipids, leading to changes in ion flux and enzyme activity (particularly phospholipase A2) at the membrane level. The release of unesterified metabolites of arachidonate, although reflecting islet lipoxygenase activity, may be an epiphenomenon. PMID- 3086651 TI - Effect of glucose on amphetamine-induced motor behavior. AB - The effect of 1 g/kg D-glucose on amphetamine-induced increases in activity; stereotypy; and rotation in rats with unilateral 6-OHDA lesions of nigro-striatal neurons was examined. The amphetamine dose-response curve for stereotypy was shifted to the right by glucose but retained the same slope as the control curve, suggesting that glucose competes for amphetamine or dopamine receptors that mediate this behavior. The slope of the dose-response curve for activity was significantly decreased by glucose, suggesting that glucose reduces activity levels in a manner that is non-competitive with the action of amphetamine or dopamine. Amphetamine-induced turning was unaffected by glucose at all doses tested. These data suggest that the effect of amphetamine on each of the three motor behaviors may be mediated by different dopamine-containing neurons, or by different post-synaptic dopamine receptors. The findings are also consistent with other data suggesting that glucose antagonizes dopamine function, but they suggest that this antagonism may not be uniform over all dopaminergic neurons or receptor types. PMID- 3086650 TI - Opioid control of LH secretion in humans: menstrual cycle, menopause and aging reduce effect of naloxone but not of morphine. AB - A number of studies have been made on the role played by endogenous opioid peptides in the secretion of LH in humans. However no previous studies have compared the effects of the most potent pharmacological agonist and antagonist, morphine and naloxone, in the same subjects. The present study examined the acute effects of injections of morphine and naloxone on plasma LH levels in 30 healthy subjects (18 women and 12 men). Fertile women were subdivided into follicular (n = 6) and luteal (n = 6) phase groups; the remaining 6 were postmenopausal women. The 12 men were sub-divided in two groups of 6 subjects according to age (24-33 years, and over 60 years). There was a two day interval between injection studies in the same subjects. Morphine significantly decreased plasma LH levels in all groups examined (P less than 0.01). On the other hand, naloxone caused a significant increase in plasma LH levels in fertile women during the luteal phase of the cycle, but not during the follicular phase or in postmenopausal subjects, and in young but not in aged men (P less than 0.01). These results indicate that in humans there is a change in the activity of the opioids regulating LH secretion during the menstrual cycle, after menopause and in aged men and that these may be studied by the use of naloxone. The inability of naloxone under certain conditions to increase LH levels reflects the decreased activity of the endogenous system, while morphine, being active in all the subjects, seems to be less discriminative, at least in physiological conditions. PMID- 3086652 TI - Calories, fat and cancer. AB - The experiments reported are part of our effort to dissociate the tumor-enhancing effects of dietary fat and high caloric intake. Rats either were fed ad libitum diets containing 4% corn oil or their calories were restricted by 40% and their diets contained 13.1% corn oil. Incidence of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors was 80% in rats fed ad libitum and 20% in those fed the calorie-restricted diets. Incidence of 1,2-dimethylhydrazine (DMH)-induced colon tumors was 100% in rats fed ad libitum and 53% in those whose caloric intake was restricted by 40%. The tumor yield (tumors per tumor-bearing rat) was significantly lower in rats on caloric restriction. In another series, rats were fed diets containing 5, 15 or 20% corn oil ad libitum or were fed calorie restricted (by 25%) diets which provided 20 or 26.6% corn oil (therefore, the same absolute amount of fat was consumed in each of the pair-fed groups). Tumor incidence and tumor yield in the two calorie-restricted groups were similar to those seen in the rats fed 5% fat ad libitum; tumor burden (total g of tumor) was 45-65% lower in the calorie-restricted rats. The data suggest that caloric intake is a more stringent determinant of tumor growth than fat intake. PMID- 3086653 TI - Mammary tumorigenesis in rats fed diets high in lard. AB - Studies were performed to examine the effect of a lard diet on tumorigenesis by 7,12-dimethylbenzanthracene (DMBA), given parenterally rather than by gavage, to eliminate any effect of the high lard diet on carcinogen absorption. In addition, the effect of low dietary levels of the antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) in the tumor model was evaluated. The lards fed were analyzed for fatty acid composition and content of certain potential contaminants. DMBA induced tumors when given by intravenous or subcutaneous injection. The high lard diet appeared to enhance tumorigenesis in rats given a dose of 0.25 mg (10% of the gavage dose) by injection into the mammary gland, although the effect was not statistically significant. In other experiments using lard from different sources and DMBA given by gavage, significant enhancement of tumorigenesis was limited to groups fed the high lard diets throughout the experiment or beginning after DMBA exposure. In contrast to earlier results, there was no demonstrable effect of feeding the high lard diets before DMBA administration. Addition of BHA and BHT to the lard at the concentration assayed in commercial lard samples or at the maximum concentration permitted did not influence the tumorigenesis. In groups in which tumorigenesis was enhanced by the high lard diet, the incidence of malignant, invasive tumors was higher than in other groups. PMID- 3086654 TI - Dietary polyunsaturated fat in relation to mammary carcinogenesis in rats. AB - High fat diets promote the development of mammary tumors induced in rats by 7,12 dimethylbenz(a)anthracene (DMBA), and polyunsaturated fats are more effective than saturated fats. This difference is related to the linoleic acid content of polyunsaturated vegetable oils, but the amount of linoleate required for maximum tumor promotion appears to be higher than indicated by earlier experiments. Comparison of the effects of a polyunsaturated vegetable oil (corn oil) containing linoleate with a fish oil (menhaden oil) containing polyunsaturated fatty acids derived from linolenic acid showed that higher dietary levels of corn oil increased the yield of DMBA-induced mammary tumors, while corresponding levels of menhaden oil had an inhibitory effect. This is further evidence that promotion of mammary tumorigenesis by polyunsaturated vegetable oils may be mediated by prostaglandins or other biologically active eicosanoids derived from n-6 fatty acids. PMID- 3086655 TI - Needle catheter feeding jejunostomy: indications and complications. PMID- 3086656 TI - Magnetic field dependence of solvent proton relaxation rates induced by Gd3+ and Mn2+ complexes of various polyaza macrocyclic ligands: implications for NMR imaging. AB - The magnetic field dependence of the solvent water proton longitudinal relaxation rate 1/T1 (the NMRD profile) has been measured for solutions of chelates of Gd3+ and Mn2+ ions with two different polyaza macrocyclic ligands: 1,4,7 triazacyclononane-N,N',N",-triacetic acid (NOTA) and 1,4,7,10 tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA). Studies were carried out mainly near physiological pH, but the pH dependence was also examined in some cases. The results are compared with published data for complexes of Gd3+ and Mn2+ ions with ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA). Competition experiments for the NOTA and DOTA chelates with EDTA and DTPA were also performed. It is found that, over the field range in which NMR imaging is currently being done, different symmetries of otherwise similar chemical ligands can alter 1/T1 of solvent protons by factors of up to three. The ligand environment can influence the relaxation times of the electronic spin moments of the ions, as well as their coordination number, thereby changing both the inner and outer sphere contributions to the relaxivities of the complexes. The relevance of these results to questions of efficiency and toxicity of these chelates as agents for enhancement of contrast in NMR images is discussed. PMID- 3086657 TI - Thyroid gland volume and thyroid function during and after acute hepatitis infection. AB - Thyroid function, the occurrence of goiter, and ultrasonically determined thyroid gland volume were investigated in 23 consecutive nonalcoholic patients with acute viral hepatitis during and six months after recovery, and compared with data obtained from 23 matched controls. Seven patients had clinically detectable goiter during disease, but only one after recovery (P less than 0.05). Median thyroid volume was 28 mL (range 15 to 42 mL) compared with 18 mL (range 12 to 27 mL) after recovery (P less than 0.001), and 17 mL (range 11 to 24 mL) in the controls (P less than 0.001). During acute hepatitis, serum levels of thyroxine, thyroxine binding globulin, and free thyroxine index were significantly increased while triiodothyronine and thyrotropin levels were unaltered and triiodothyronine resin uptake and free triiodothyronine index levels were decreased. After recovery all thyroid variables were normalized. In conclusion, acute liver disease was associated with a marked increase in thyroid volume, but the study did not clarify the mechanism underlying thyroid enlargement. PMID- 3086658 TI - Effect of duration of diabetic state on insulin action in isolated rat soleus muscles. AB - We studied the effect of the duration of diabetic state on insulin action in skeletal muscle by measuring insulin binding, 2-deoxyglucose uptake, and intracellular glucose metabolism in isolated soleus muscles from streptozotocin induced diabetic rats. Insulin binding to soleus muscles from diabetic rats was increased over that from controls. Glucose transport activity was determined by measuring the 2-deoxyglucose uptake at the concentration of 1 mmol/L at 25 degrees C. In the rats with diabetes of one week duration, insulin-stimulated 2 deoxyglucose uptake was not impaired, whereas basal 2-deoxyglucose uptake was decreased. However, the diabetic rats with two weeks duration revealed a 35.6% decrease in the insulin-stimulated 2-deoxyglucose uptake. Furthermore, four week duration of diabetic state led to a 60% decrease both in basal and insulin stimulated 2-deoxyglucose uptake. Total glucose utilization was estimated as the total amount of glucose incorporated into muscle and lactate released into the medium following incubation at 37 degrees C, with 5 mmol/L glucose. The diabetic rats with one week duration did not demonstrate any changes in total glucose utilization both in basal and insulin-stimulated state. However more than two weeks duration of diabetes led to a 30% to 35% decrease both in basal and insulin stimulated total glucose utilization, similar to the findings in the 2 deoxyglucose uptake study. We concluded that prolonged insulinopenia led to decreased glucose transport and intracellular glucose metabolism and resulted in insulin resistance in skeletal muscles. PMID- 3086659 TI - Utilization of parenterally administered glucose oligosaccharides when infused with glucose and amino acids in postsurgical patients. AB - Utilization of intravenously administered oligosaccharides was tested in postsurgical patients by infusing them simultaneously with glucose and amino acids. Thirty two patients were infused with one of two parenteral regimens for four-day periods. Twenty-two patients received a nutritional regimen providing 46 g glucose, 32.5 g amino acids, and 45 g oligosaccharides per liter, while the remaining ten patients received the same solution without oligosaccharides. Patients infused with the test solution received an overall four-day mean +/- SD of 106 +/- 24.2 g oligosaccharide per day. The mean overall four-day excretion of total glucose (free plus oligosaccharide bound) was significantly higher (P less than 0.001) in patients infused with oligosaccharides (46.1 +/- 29.0 g/d) than in reference patients (1.19 +/- 1.20 g/d). Of the total carbohydrate excreted in patients receiving oligosaccharides, 11.3 +/- 13.1 g/d were glucose, 14.8 +/- 13.1 g/d were maltose plus maltotriose, and 20.8 +/- 19.3 g/d were oligosaccharides of maltotetraose size or larger. Although overall utilization of infused oligosaccharide for all patients was only 58.5% +/- 23.1%, three of the patients showed unexpectedly good utilization (94.6% +/- 1.24%). PMID- 3086660 TI - Relationships of serum lipoproteins and apoproteins to sex hormones and to the binding capacity of sex hormone binding globulin in healthy Finnish men. AB - We have determined the levels of serum sex hormones, the binding capacity of sex hormone binding globulin (SHBG), urinary estrogens, serum lipids, lipoproteins, and apolipoproteins A-I, A-II, and B in 30 healthy middle-aged Finnish men with similar dietary habits. Serum levels of total testosterone, free testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), and the binding capacity of SHBG were all positively correlated to high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) (r = .43 to .80, P less than 0.05 to 0.001). Total testosterone and 5 alpha-DHT showed a positive correlation to the ratio of apo A I to Apo A-II (r = .37, P less than 0.05 and r = .58, P less than 0.01, respectively). Serum estradiol levels were negatively correlated to serum total cholesterol, low density lipoprotein cholesterol (LDL), and Apo B (r = -.51 to .56, P less than 0.01). Moreover, serum free estradiol was negatively correlated to HDL-C and Apo A-I (r = -.46 and r = -.50, P less than 0.01). In multiple linear regression analysis, 5 alpha-DHT was the most significant independent determinant of HDL-C and apo A-I levels when androgens, luteinizing hormone, estradiol, binding capacity of SHBG, and exogenous factors such as age, body mass index (BMI), smoking, alcohol consumption, and diet were taken into account. Multivariate analysis also demonstrated that both total and free estradiol were inversely related to serum Apo B levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086661 TI - Measurement of growth hormone-releasing factor. PMID- 3086662 TI - Assay of growth hormone-releasing factor. PMID- 3086663 TI - Measurement of phospholipid turnover in cultured hormone responsive pituitary cells. PMID- 3086664 TI - Computer-controlled perifusion system for neuroendocrine tissues: development and applications. PMID- 3086665 TI - Measurement of intracellular ionized calcium with aequorin. PMID- 3086666 TI - Use of lac gene fusions to study transport proteins. PMID- 3086667 TI - Methods for mutagenesis of the bacterioopsin gene. PMID- 3086668 TI - Generation of a protonmotive force in anaerobic bacteria by end-product efflux. PMID- 3086669 TI - Anion exchange in bacteria: reconstitution of phosphate: hexose 6-phosphate antiport from Streptococcus lactis. PMID- 3086671 TI - Serological and pyocin typing and antibiotic sensitivity of Pseudomonas aeruginosa strains. AB - 94 strains of Pseudomonas aeruginosa, isolated from hospitalized patients, were typed with serological and pyocinic methods, also testing their sensitivity to 6 antibiotics. The serological method allowed for the typing of almost all the strains (98.9%), (the 0-11 serotype was the most frequent -23.4%-) vs. 80.6% by the pyocinic method. Among those tested, ceftazidime was the most active antibiotic, against the P. aeruginosa strains examined. PMID- 3086670 TI - Identification and physical characterization of yeast glucoamylase structural genes. AB - Each one of at least three unlinked STA loci (STA1, STA2 and STA3), in the genome of Saccharomyces diastaticus controls starch hydrolysis by coding for an extracellular glucoamylase. Cloned STA2 sequences were used as hybridization probes to investigate the physical structure of the family of STA genes in the genomes of different Saccharomyces strains. Sta+ strains, each carrying a single genetically defined STA locus, were crossed with a Sta- strain and the segregation behavior of the functional locus (i.e. Sta+) and sequences homologous to a cloned STA2 glucoamylase structural gene at that locus were analyzed. The results indicate that in all strains examined there is a multiplicity of sequences that are homologous to STA2 DNA but that only the functional STA loci contain extensive 5' and 3' homology to each other and can be identified as residing on unique fragments of DNA; that all laboratory yeast strains examined contain extensive regions of the glucoamylase gene sequences at or closely linked to the STA1 chromosomal position; that the STA1 locus contains two distinct glucoamylase gene sequences that are closely linked to each other; and that all laboratory strains examined also contain another ubiquitous sequence that is not allelic to STA1 and is nonfunctional (Sta-), but has retained extensive sequence homology to the 5' end of the cloned STA2 gene. It was also determined that the DEX genes (which control dextrin hydrolysis in S. diastaticus), MAL5 (a gene once thought to control maltose metabolism in yeast) and the STA genes are allelic to each other in the following manner: STA1 and DEX2, STA1 and MAL5, and STA2 and DEX1 and STA3 and DEX3. PMID- 3086672 TI - Proteases of the pathogenic neisseriae: possible role in infection. AB - Proteolytic enzymes are produced by animal as well as human pathogens. Several micro-organisms including Neisseriae produce IgA1 specific proteases. This protease specifically hydrolyses IgA1 protein. IgA1-specific protease(s) synthesized by Neisseria species are briefly reviewed with particular reference to their role in infection. PMID- 3086673 TI - Isolation and characterization of a lipopolysaccharide-specific bacteriophage of Pseudomonas aeruginosa. AB - Phage H22 was isolated from sewage using Pseudomonas aeruginosa NCTC 8505 (serotype 0:3) as the host. Although not O-specific, this phage was found to have lipopolysaccharide (LPS) as a receptor. The broad host-range and lack of O specificity of the phage suggested that its receptor site was in the core region of the LPS. Phage H22 had a Bradley type A structure. It was unaffected by chloroform and diethyl ether, and was stable between pH 5 and 8 and in the temperature range 0 to 60 degrees C. The adsorption rate constant was 14.6 X 10( 9) ml min-1. The phage had a latent period of 43 min, with a rise time of 18 min and a burst size of 6. The adsorption of phage to whole cells and LPS occurred over a broad pH range. Maximum adsorption occurred at 50 degrees C and pH 7.5 in the presence of 0.001 M Ca2+. PMID- 3086674 TI - The role of lipopolysaccharide as a receptor for some bacteriophages of Pseudomonas aeruginosa. AB - Typing phages of the Colindale typing set for Pseudomonas aeruginosa have been tested for the use of lipopolysaccharide (LPS) as a receptor. Studies using the reference strains of the International Antigenic Typing Scheme for O-serotypes of P. aeruginosa supported earlier indications that none of the phages were O specific. Studies of the adsorption of phages to LPS showed that typing phages 16, 44, F8, 68, 109, 352, and 1214 (as well as other phages 2 and H22) were LPS specific, but were not consistently adsorbed by isolated LPS from all sensitive strains. Water-soluble fractions from LPS did not adsorb phages and did not inhibit their neutralization by whole LPS. No endoglycosidase activity against LPS was detected for any phage. The significance of these results for the roles of LPS in the adsorption process and phage sensitivity are discussed. PMID- 3086675 TI - Purification of scrapie agent from infected animal brains and raising of antibodies to the purified fraction. AB - The fraction (P4) containing scrapie infectivity was obtained by treatment of scrapie-infected mouse brains with the detergent sarcosyl, differential centrifugation, and proteolytic enzyme digestion. Scrapie infectivity in the P4 fraction was purified 239-2,390 times with respect to protein. Similar fractions were also prepared from the brain of a sheep naturally infected with scrapie. Morphological observation of the P4 fractions revealed that the main components were unique rods of 3-5 X 60-200 nm, which resembled scrapie-associated fibrils (SAF) or prion rods. The P4 fractions formed three major broad bands of polypeptides with molecular weights (MWs) of about 24.5K, 21K, and 17K dalton (Kd) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and some low MW polypeptides were also present in the fraction. Rabbits immunized with this fraction prepared from mouse brains raised antibodies against the three major polypeptides. PMID- 3086676 TI - The production of a cytotoxic factor by mouse peritoneal macrophages and macrophage hybridomas treated with various stimulating agents. AB - Murine peritoneal macrophages elicited with a streptococcal preparation, OK-432, produced as much of a cytotoxic factor after stimulation with lipopolysaccharide (LPS) as BCG-elicited macrophages did. Proteose peptone-elicited macrophages produced a very small amount, if any, of the factor, and resident peritoneal macrophages did not release it at all even after LPS-stimulation. A newly established macrophage hybridoma, D/O-3.3, produced the factor after LPS stimulation, but another hybridoma, D/O-3.2, did not. Experiments using these peritoneal macrophages and macrophage hybridomas demonstrated that macrophages can be divided into three subpopulations with regard to stages of activation for production of the cytotoxic factor. The first is fully activated macrophages which produce the factor after stimulation with LPS or MAF-C alone, the second is partially activated macrophages which produce the factor only after stimulation with a combination of recombinant interferon-gamma (rIFN-gamma) and LPS or rIFN gamma and macrophage activating factor for cytotoxicity (MAF-C), and the third is nonactivated macrophages which cannot produce the factor at all. PMID- 3086677 TI - Impairment of T cell-mediated immunity to Listeria monocytogenes in pregnant mice. AB - In order to study pregnancy-induced changes in cell-mediated immunity to Listeria monocytogenes, acquired resistance and T cell functions in pregnant mice were compared with those in nonpregnant mice after immunization with viable listerial cells. Impaired generation of acquired resistance was evident in pregnant mice from the impaired elimination of bacteria and poor survival after secondary challenge. Delayed footpad reactivity to listerial antigen was also lower in the pregnant mice. When immune spleen cells were examined for their ability to produce macrophage activating factor in vitro, culture supernatants from pregnant mouse spleen cells with listerial antigen showed far less ability to render macrophages cytostatic for P815 mastocytoma cells. To elucidate further the impairment of listeria-immune T cell generation in pregnant mice, a local transfer experiment was carried out. When a given number of immune spleen cells was transferred locally into the footpads of naive mice, both delayed footpad reaction and local protection were much lower in the pregnant mice. This local transferability of the reactions was abrogated after treatment of cells with anti Thy 1 antibody plus complement. These findings indicate that pregnancy impairs the generation of specific T cells capable of contributing to acquired resistance to L. monocytogenes. Possible mechanisms for this impairment and the relationship to macrophage functions are discussed. PMID- 3086678 TI - Evaluation of a commercially available latex immunoagglutination test kit for detection of Clostridium difficile D-1 toxin. PMID- 3086679 TI - Naturally occurring cardiac glycosides. AB - Cardiac glycoside poisoning from the ingestion of plants, particularly of oleanders, occurs with reasonable frequency in tropical and subtropical areas. We have assessed a variety of plant specimens for their cardiac glycoside content by means of radioimmunoassays with antibodies that differ in their specificity for cardiac glycosides. Significant amounts of immunoreactive cardiac glycoside were found to be present in the ornamental shrubs: yellow oleander (Thevetia peruviana); oleander (Nerium oleander); wintersweet (Carissa spectabilis); bushman's poison (Carissa acokanthera); sea-mango (Cerbera manghas); and frangipani (Plumeria rubra); and in the milkweeds: redheaded cotton-bush (Asclepias curassavica); balloon cotton (Asclepias fruiticosa); king's crown (Calotropis procera); and rubber vine (Cryptostegia grandifolia). The venom gland of the cane toad (Bufo marinus) also contained large quantities of cardiac glycosides. The competitive immunoassay method permits the rapid screening of specimens that are suspected to contain cardiac glycosides. Awareness of the existence of these plant and animal toxins and their dangers allows them to be avoided and poisoning prevented. The method is also useful for the confirmation of the presence of cardiac glycosides in serum in cases of poisoning. PMID- 3086680 TI - High-dose radiotherapy for localized prostatic cancer. An analysis of treatment results and early complications. AB - Between 1970 and 1983, 477 consecutive patients with clinically localized prostatic adenocarcinoma were treated with primary external-beam radiotherapy. With a minimum follow-up period of 60 months, the five- and 10-year survival rates were 59% and 33%, respectively. The five-year survival rate was 89% for patients with stage-A disease, 59% for stage-B disease and 25% for stage-C disease; it was 79% for patients with well-differentiated carcinomas, but only 37% for patients with high-grade tumours. The over-all local in-field control rate was 88%. Local failure occurred in 6% of patients with stage-A disease, 11% with stage-B disease, and 18% with stage-C disease. All patients experienced some radiation-induced reactions, but these were significant in only 14.2% of cases. The role of local- versus extended-field radiotherapy for curative treatment of prostatic cancer is discussed in some detail. Our unexpectedly low over-all survival figures emphasize the need to exclude the presence of distant metastases as fully as possible before commencing radical radiotherapy. High-dose radiotherapy to localized prostatic cancer offers significant advantages over radical surgery and is associated with an excellent local control rate, which can be achieved with an acceptable degree of early morbidity. PMID- 3086681 TI - Drug interactions with the pill. PMID- 3086682 TI - Oral nitroglycerin spray. PMID- 3086684 TI - On the limits of expanding health care reform: chronic care in prepaid settings. AB - Health Maintenance Organizations have become a favored vehicle for reform of the American health care system, while controlling costs and assuring quality. But for populations with a high prevalence of chronic disease--the elderly or the mentally ill--HMOs may fall short of meeting needs. Three stages of reform are proposed for adapting the principle of prepayment to better serve enrollees with chronic illness. PMID- 3086683 TI - [Evolution of the interrelation of the linking members in the Leishmania parasite system]. PMID- 3086685 TI - Distance and the use of mental health services. AB - The inverse relationship between distance from mental health services and their use has been noted over many decades and on several continents. Although many factors--diagnostic, socioeconomic, and nosocomial--may modify this correlation, its persistence is remarkable. As other barriers to use are diminished, distance remains a mutable variable for planning more effective use of many health care services. PMID- 3086686 TI - [Reticulo-histiocytic system and metabolic storage pathology with reference to intraoral manifestations]. PMID- 3086687 TI - [von Recklinghausen's neurofibromatosis. The oral aspects of a clinical case]. PMID- 3086688 TI - Creutzfeldt-Jakob disease. AB - There has been significant advance in our understanding of CJD and similar spongiform encephalopathies in recent years. The range in clinical expression of the disease is better appreciated, and the existence of "atypical" cases of CJD is increasingly recognized. New ideas about the possible modes of natural transmission have been derived from case-control studies in different parts of the world. PMID- 3086689 TI - Ethical and legal aspects of dementia. AB - Medical ethical dilemmas regarding life-sustaining treatment in elderly and demented patients are becoming increasingly commonplace and complex. In dealing with these situations, health care providers must ensure that a patient's rights are balanced against society's needs. To help medical professionals understand these issues, the authors describe the distinction between substantive standards and procedural guidelines as well as the interrelationship between the two. It is only when careful procedural steps are followed after thoughtful consideration is given to the substantive issues that termination of treatment decisions will be made in the best possible context. PMID- 3086690 TI - Arboviral infections of the central nervous system--United States, 1985. PMID- 3086691 TI - Premature mortality due to unintentional injuries--United States, 1983. PMID- 3086692 TI - Premature mortality due to suicide and homicide--United States, 1983. PMID- 3086693 TI - Measles--United States, 1985. PMID- 3086694 TI - Hepatitis B associated with jet gun injection--California. PMID- 3086695 TI - Rapid nutritional status evaluation during drought conditions--Republic of Niger. PMID- 3086697 TI - Non-A, non-B hepatitis associated with a factor IX complex infused during cardiovascular surgery--Arizona. PMID- 3086696 TI - Salmonellosis outbreaks associated with commercial frozen pasta--Massachusetts, New Jersey, New York. PMID- 3086698 TI - Occupational exposures to formaldehyde in dialysis units. PMID- 3086699 TI - Genital herpes infection--United States, 1966-1984. PMID- 3086700 TI - Hysterectomy among women of reproductive age, United States, update for 1981 1982. PMID- 3086701 TI - Nosocomial infection surveillance, 1984. PMID- 3086702 TI - Foodborne disease outbreaks, annual summary, 1982. PMID- 3086703 TI - [Hyperbilirubinemia in neonates associated with total parenteral nutrition]. AB - Clinical studies on the pathogenesis of hyperbilirubinemia (HB) in neonates during total parenteral nutrition (TPN) were performed. From 1971 to 1982, 77 neonates underwent TPN for more than 2 weeks in our institutions. Forty-four of them (57.2%) developed HB during the first one month of life. Twenty eight of 32 patients (87.5%) with dominant infection developed hB, while only 16 of 45 (35.6%) without infection developed HB. Patients with any kind of obstructive intestinal diseases evoked HB more commonly than patients with other diseases. In addition, HB occurred more often in the patients receiving more than 110 kcal/kg/day than those receiving less than that. Gestational ages, birth weights, the duration of TPN and fasting periods had no significant influence on the occurrence of HB. PMID- 3086704 TI - [Coagulation studies in patients after abdominal surgery]. AB - Coagulation studies were performed in patients who underwent abdominal surgery. One hundred and twenty six patients with cholelithiasis, peptic ulcer and gastric cancer were examined. Although fibrinogen increased up to 560 mg/dl postoperatively, DIC did not occur among these patients, at all. For 30 patients who underwent hepatectomy, esophageal transection or pancreatoduodenectomy, HPT, PT, fibrinogen, platelet count, alpha 2-PI, AT-III, plasminogen and DIC score were investigated until 10 postoperative days. As for 13 patients without liver cirrhosis in this group, deterioration of HPT, PT and AT-III was noted on the second postoperative day, however these parameters improved on the fifth postoperative day and all patients recovered uneventfully. On the contrary, as to patients with liver cirrhosis, changes of coagulation parameters were drastic. Significant decrease of HPT, PT, AT-III, plasminogen and increase of FDP and DIC score were noted after operation and these values deteriorated with time in certain cases. Seven patients out of 17 died of DIC and multiple organ failure. More than half of these patients received Gabexate Mesilate (GM) injection in a dose of 1200 mg/day postoperatively for more than 5 days to prevent DIC. In patients who underwent hepatectomy due to hepatocellular carcinoma with liver cirrhosis, the increase of FDP and DIC score seemed to be inhibited by GM on the fifth postoperative day. PMID- 3086705 TI - [Recent development and trends in adjuvant chemotherapy in the surgical field]. PMID- 3086706 TI - [Heterotopic liver allotransplantation in dogs utilizing intraportal hyperalimentation]. AB - Heterotopic liver transplantation utilizing intraportal hyperalimentation was studied in dog for the purpose of temporary hepatic support for acute liver failure. The liver graft was transplanted in the right lower abdomen of the recipient, and its suprahepatic IVC was anastomosed end-to-side to the infra renal IVC of the recipient. The celiac artery of the graft was anastomosed end-to end to the right internal iliac artery of the recipient. An infusion catheter was placed in the donor's portae and intraportal hyperalimentation with insulin was performed. A polyethylene tube (1.7 mm bore) was inserted into the CBD of the graft and led through the body wall as an external biliary drain, after which the recipient's CBD was ligated and transected. The grafts functioned well and excreted bile for 6 days in a non-immunosuppressed group and until death in an immunosuppressed group. Serum bilirubin levels of the recipients increased slightly or were within normal range. At autopsy, the grafts showed no atrophy. Heterotopic liver transplantation with intraportal hyperalimentation will be useful as a temporary hepatic support for acute liver failure in the future. PMID- 3086707 TI - Hormone-stimulated redistribution of gonadotrope protein kinase C in vivo: dependence on Ca2+ influx. AB - In the present study we show that natural sequence gonadotropin-releasing hormone (GnRH) and a high affinity, metabolically stable agonist (Buserelin) promote redistribution of protein kinase C (PKC) activity to a particulate fraction prepared from anterior pituitary. The action of the agonists, administered in vivo to ovariectomized rats, is both time and dose dependent. GnRH antagonist alone does not measurably alter distribution of this enzymatic activity but inhibits the ability of GnRH to do so and to stimulate luteinizing hormone release. This finding indicates that receptor occupancy alone is insufficient to cause PKC redistribution. Redistribution of PKC in response to Buserelin is inhibited by the calcium ion channel antagonist methoxyverapamil (D600), suggesting that redistribution of PKC activity, like GnRH-stimulated gonadotropin release, requires the influx of extracellular calcium. PMID- 3086708 TI - DNA alkylation by enzyme-activated mitomycin C. AB - After anaerobic reductive activation by either NADPH cytochrome P-450 reductase (EC 1.6.2.4) or xanthine oxidase (EC 1.2.3.2), mitomycin C readily alkylated DNA. When the mitomycin C-alkylated DNA is digested by DNase, snake venom phosphodiasterase, and alkaline phosphatase, only partial release of the monofunctionally linked mitomycin C nucleotide adduct occurs. Cross-linked adducts are not released into dinucleotides but resist nuclease digestion and remain in oligonucleotides and insoluble precipitates. Kinetic analyses show that the nuclease-resistant fraction which is indicative of DNA cross-linking by mitomycin C takes place quite readily. This nuclease-resistant fraction is particularly significant when the amount of total bound mitomycin C is less than 15 mumol/mmol of DNA. The cross-linked mitomycin C product accounts for more than half of the total alkylation under all pH conditions tested. Our data suggest that particular DNA sites are available for DNA cross-linking by mitomycin C, and these sites are probably the preferred and immediate alkylating targets. Furthermore, DNA cross-links by mitomycin C are not the secondary product of monofunctional adducts. Activity of both flavoenzymes is pH dependent, hence, mitomycin C activation and the rate of DNA alkylation are pH dependent. At elevated mitomycin C alkylation of DNA, the highest amount of cross-linking occurs at neutral pH. High pressure liquid chromatographic separation of the nuclease-digested DNA detected one major and two less prominent mitomycin C adducts. These were verified to be mononucleotide mitosene types by UV spectra showing maximum absorbance at 312 and 250 nm. The major adduct was purified and identified as O6-(2'-deoxyguanosyl)-2,7-diaminomitosene by NMR, indicating that the O6 position of guanine is a preferred site in DNA for at least monofunctional linkage formation. PMID- 3086710 TI - Amino acid sequence of a light chain variable region of a human rheumatoid factor of the Wa idiotypic group, in part predicted by its reactivity with antipeptide antibodies. AB - Antipeptide antisera were raised to the second and third complementarity determining regions of the light chain derived from a human monoclonal IgM (Sie) which had antigammaglobulin activity and belonged to the Wa cross-reactive idiotypic group of human rheumatoid factors, two of whose members (Sie, Wo1) had been previously sequenced in our laboratory (Andrews and Capra, Biochemistry 20, 5816-5822, 1981). These antisera were found to react with the light chain of another human monoclonal IgM (Go1) that shared the Wa idiotype while antipeptide antisera made to the third CDR of the Sie heavy chain failed to react. The amino acid sequence of the variable region of the Go1 light chain was found to be highly homologous to the light chain of Sie from which the synthetic peptides were derived, particularly in the framework regions and the second and third CDR. This study illustrates that antipeptide antisera are valuable and specific probes for determining the relationship between molecules which exhibit similar antigen binding or idiotypic specificities and, furthermore, such antisera are able to predict amino acid sequences with surprising precision. PMID- 3086709 TI - Polyamine depletion increases cellular ribonucleotide levels. AB - Depletion of the putrescine and spermidine content of Ehrlich ascites tumor cells by alpha-difluoromethylornithine (DFMO) treatment results in at least a 1 500 fold increase in the decarboxylated S-adenosylmethionine (deSAM) content. The accumulation of this adenine nucleoside occurs because of the absence of putrescine and spermidine to act as aminopropyl group acceptors in the spermidine and spermine synthase reactions and because of an increase in S adenosylmethionine decarboxylase activity. The fact that the synthesis of deSAM continues in DFMO-treated cells makes the pathway an adenine trap. This prompted a study of the adenine nucleotide pools. High-performance liquid chromatographic analysis showed that the total adenine nucleotide pool increased, rather than decreased, as a result of DFMO treatment; the major contributors to the increase being ATP and ADP, which increased 2.6 and 1.9 times, respectively. The cellular content of other ribonucleotides increased as well, particularly that of UTP and CTP. When putrescine was added together with DFMO, the increases in cellular ribonucleotide contents were prevented, showing that they were indeed caused by polyamine depletion. PMID- 3086711 TI - Analysis of the specificity of natural human antibody reactive to Actinomyces. AB - The specificity of a frequently-occurring precipitin response to soluble antigens from cell-walls and culture filtrates of A. viscosus ATCC 19246 was examined. After precipitation with isopropanol (50-75% v/v), antigen fractions of different charge and molecular weight were isolated by ion exchange and gel filtration. When heated in mineral acid or alkali above 0.15 M, each of the purified antigens lost precipitating activity, but now inhibited the precipitin reaction between serum and exogenous unheated antigen. The inhibitor was isolated over Biogel P30 and characterized as a peptide fragment (mol. wt about 2 kd) containing approximately 50 moles of ornithine and 6-12 moles, respectively, of aspartate, serine, threonine, glutamate, glycine, alanine and histidine per 100 moles amino acids. The inhibitor was totally destroyed by heating for 1.0 hr in 2.0 M HCl. Variability in the number of fragments and differences in the non-antigenic portions probably accounted for the complexity of the antigens. Ornithine, putrescine, N-acetyl putrescine and various sugars had little or no effect on the precipitin reaction with intact antigen at high concentrations (200 mM), whereas the fragment inhibited completely at 0.4 mM. This indicates that neither ornithine nor its side-chain amides are exclusively recognized by antibody. However, ornithine may be part of a larger sequence and/or important in forming the configuration recognized by the human antibodies. PMID- 3086712 TI - Possible involvement of phosphorylation of a 36,000-dalton protein of rat basophilic leukemia (RBL-2H3) cell membranes in serotonin release. AB - Phosphorylation of a 36,000-dalton (36k-Da) protein of rat basophilic leukemia (RBL-2H3) cell membranes was investigated. This phosphoprotein has been suggested to be the beta-subunit protein of the immunogloblin E (IgE) receptor of RBL-2H3 cells [Teshima et al., Biochem. biophys. Res. Commun. 125, 867-874 (1984)]. Phospholipids such as phosphatidyl serine, phosphatidyl inositol and phosphatidyl ethanolamine, which are known to be activators of protein kinase C, enhanced the phosphorylation of the 36K-Da protein. In contrast, 1-(5-isoquinoline sulfonyl)-2 methylpiperazine (H-7) which has been identified as a potent inhibitor of protein kinase C in vitro decreased incorporation of radioactive phosphate from [gamma 32P]ATP into this protein. These results indicate that the phosphorylation of the 36K-Da protein of RBL-2H3 cell membranes is catalyzed by protein kinase C. H-7 also inhibited the release of serotonin from RBL-2H3 cells stimulated with an antigen or calcium ionophore A23187 and 12-O-tetradecanoyl phorbol 13-acetate (TPA). Treatment of the antigen-stimulated cells with TPA caused a synergistic effect on the serotonin release. A similar effect was obtained by treatment of A23187-stimulated cells with TPA or 1-oleoyl-2-acetyl glycerol. PMID- 3086713 TI - Mutagenicity of nickel sulphate in Drosophila melanogaster. AB - Nickel sulphate was injected into Drosophila melanogaster males at different concentrations in order to test the chemical for the induction of SLRL and SCL in germ cells. Nickel sulphate induced SLRL at concentrations tested, with the peak of activity at premeiotic and postmeiotic stages. It failed to produce SCL except at the highest concentration tested, where induction of XO males was significant for the pooled data. PMID- 3086714 TI - Micronuclei and other nuclear anomalies induced in various organs by diethylnitrosamine and 7,12-dimethylbenz[alpha]anthracene. PMID- 3086715 TI - Sensitivity to DNA-damaging agents and mutation induction by UV light in UV sensitive CHO cells. AB - Three UV-sensitive (UVs) mutants isolated from a CHO cell line were analyzed for survival after exposure to H2O2, EMS, MMC, CCNU, X-rays and for mutation induction after UV-irradiation. The UVs mutants showed normal sensitivities to EMS and H2O2, whereas they were hypersensitive to the bifunctional alkylating agents MMC and CCNU and to hypoxic X-irradiation. Compared to parental cells, one of the UV-sensitive clones showed approximately 3- and 7-fold enhancement in the mutagenic response per unit UV dose for 6-thioguanine and ouabain resistance, respectively. PMID- 3086716 TI - Mutagenic activation of aflatoxin B1 by several forms of purified cytochrome P 450. AB - Metabolic activation by several forms of purified cytochrome P-450 of aflatoxin B1 to a product(s) mutagenic to Salmonella typhimurium TA100 was examined. Of the 5 forms of cytochrome P-450 purified from liver microsomes of untreated and PCB treated male rats, a constitutive form purified from untreated male rats, P-450 male, and a high-spin form of cytochrome P-450, P-448-H, from PCB-treated rats were highly active. PMID- 3086718 TI - Effects of pretreatment with 2,3,7,8-tetrachlorodibenzofuran on microsomal monooxygenase activity in Drosophila melanogaster. AB - The effects of tetrachlorodibenzofuran pretreatment was studied in microsomes from adult Drosophila of the Karsnas 60w strain. Pretreatment for 18 h with 0.2 or 1 mg TCDBF did not increase benzo[alpha]pyrene monooxygenase activity, 7 ethyoxyresorufin deethylase activity or the formation of 2-, 3- or 4-hydroxylated metabolites from biphenyl, in accordance with previous results with alpha naphthoflavone pretreatment. The results suggest that adult Drosophila is non responsive to induction by polycyclic aromatic hydrocarbons. The role of the TCDD receptor, which has been reported to be present in Drosophila, is obscure against this background. The implications for mutagenicity testing in Drosophila is discussed. PMID- 3086717 TI - Results of the rec-assay of nitropyrenes in the Bacillus subtilis test system. AB - The rec-assay of the nitropyrenes in Bacillus subtilis was performed. All nitropyrene derivatives were positive in this system. Especially, 3 isomers of 1,3-, 1,6- and 1,8-dinitropyrene and 4-nitropyrene were found to possess strong DNA-damaging capacities at extremely low concentrations. PMID- 3086719 TI - Cost and research. PMID- 3086720 TI - Length of hospital stay for femoropopliteal bypass. PMID- 3086722 TI - Use of the term "cost effective". PMID- 3086721 TI - Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. AB - Children with sickle cell anemia have an increased susceptibility to bacterial infections, especially to those caused by Streptococcus pneumoniae. We therefore conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial to test whether the regular, daily administration of oral penicillin would reduce the incidence of documented septicemia due to S.pneumoniae in children with sickle cell anemia who were under the age of three years at the time of entry. The children were randomly assigned to receive either 125 mg of penicillin V potassium (105 children) or placebo (110 children) twice daily. The trial was terminated 8 months early, after an average of 15 months of follow-up, when an 84 percent reduction in the incidence of infection was observed in the group treated with penicillin, as compared with the group given placebo (13 of 110 patients vs. 2 of 105; P = 0.0025), with no deaths from pneumococcal septicemia occurring in the penicillin group but three deaths from the infection occurring in the placebo group. On the basis of these results, we conclude that children should be screened in the neonatal period for sickle cell hemoglobinopathy and that those with sickle cell anemia should receive prophylactic therapy with oral penicillin by four months of age to decrease the morbidity and mortality associated with pneumococcal septicemia. PMID- 3086723 TI - Differentiation of leukemia cells to polymorphonuclear leukocytes in patients with acute nonlymphocytic leukemia. AB - We used recombinant-DNA techniques to determine the origin of polymorphonuclear leukocytes in patients with acute nonlymphocytic leukemia, at presentation, in remission, and in relapse. Studies using X chromosome-linked DNA polymorphisms strongly suggested that leukemic blast cells in this form of leukemia can differentiate in vivo to form mature granulocytes. Common chromosomal changes seen in blast cells, such as the addition of a chromosome 8 or the loss of a chromosome 7, were found to be present in the mature granulocytes of patients with leukemia. In addition, rearrangement of the immunoglobulin heavy-chain gene was detected in the polymorphonuclear leukocytes of one patient. Finally, we have observed the persistence of a single dominant hemopoietic clone in the granulocytes of 3 of 13 patients in complete remission. These findings demonstrate that recombinant-DNA probes can detect clonal populations of granulocytes in patients with acute nonlymphocytic leukemia, and provide further evidence that in some patients leukemic blast cells differentiate to form mature cells. PMID- 3086724 TI - Drug therapy. Tocainide. PMID- 3086725 TI - Local and systemic effects of intradermal recombinant interferon-gamma in patients with lepromatous leprosy. AB - Evidence that interferon-gamma may be a physiologic macrophage-activating factor, and that macrophage activation may be defective in lepromatous leprosy, led us to test the effects of intradermal injection of low doses of recombinant interferon gamma in six patients with this disease. Interferon-gamma, 1 or 10 micrograms, was administered daily by jet gun for three days into a single cutaneous lesion. A biopsy specimen was taken from the injection site on the sixth study day and compared with specimens obtained previously from a site where no injection had been made or where excipient alone had been injected in the same way as the interferon. Interferon-gamma elicited local effects similar to certain features of delayed-type hypersensitivity reactions or tuberculoid leprosy, including induration, T-cell and monocyte infiltration, keratinocyte proliferation, diminution of epidermal Langerhans cells, and dermal and epidermal cell HLA-DR (Ia) antigen expression. At some of the sites of interferon-gamma injection, there was also an apparent decrease in acid-fast bacilli. Before treatment, monocytes from patients with lepromatous leprosy released 48 percent as much hydrogen peroxide as did monocytes from controls in response to phorbol myristate acetate, and 36 percent as much as those from controls in response to Mycobacterium leprae. When recombinant interferon-gamma was injected, these responses became normal. No toxic effects were observed. These observations suggest that interferon-gamma can mediate certain manifestations of delayed-type hypersensitivity or cell-mediated immunity in vivo, and that recombinant interferon-gamma should be tested for possible therapeutic effects in certain nonviral infectious diseases. PMID- 3086726 TI - Bone marrow transplantation for Pompe's disease. PMID- 3086727 TI - Substrate depletion during formation of aflatoxin and kojic acid on corn inoculated with Aspergillus flavus. AB - Depletion of sugar and starch carbon sources and concomitant formation of secondary fungal metabolites, aflatoxin and kojic acid, were examined in growing corn inoculated with Aspergillus flavus. Kernels from control and inoculated ears were removed and analyzed after 16, 24, 48, 96 and 168 hrs. Reducing sugars were not significantly different for inoculated and control non-inoculated samples, but after 168 hrs (seven days) starch content was 20% lower in inoculated than in control samples. Kojic acid was detected before aflatoxins formed. Kojic acid, the oxidized product of kojic acid, and aflatoxin were all present in samples two days from inoculation. The formation of this oxidation product may influence toxin levels. PMID- 3086728 TI - Phencyclidine: an update. PMID- 3086729 TI - Modulation of phencyclidine (PCP) pharmacokinetics with PCP-specific Fab fragments. PMID- 3086730 TI - Discriminative stimulus properties of PCP mimetics. PMID- 3086731 TI - Clinical implications of behavioral pharmacology research on phencyclidine. AB - This discussion has highlighted only some of the areas of behavioral pharmacology research with PCP, focusing largely on studies in our laboratories. Some of the areas touched upon lightly have been much more extensively investigated (e.g., PCP-like properties of psychotomimetic opioids). Some areas, such as the search for a PCP antagonist, have been studied with relatively little success so far. Two other areas, among many that are worthy of mention, are the extensive series of studies of the effects of PCP on complex learning procedures, starting with the studies by Moerschbaecher and Thompson (1980a, Moerschbaecher and Thompson 1980b), and an elegant series of studies on the determinants of oral PCP self administration, beginning with the study by Carroll and Meisch (1980). Much progress has been made on the clinical implications of behavioral research with PCP, and we are in a much better position to respond effectively to this public health problem than we were when it emerged, only a little over 10 years ago. The impetus behind PCP research has come from two directions--from the emergence of PCP as a drug of abuse with the pressing practical questions raised by this epidemic, and from the potential that PCP research has for a fuller understanding of the brain and behavior. Although this discussion has focused on the former, progress toward the latter goal has been equally, if not more, substantial, and may have long-term health implications far beyond those presented by problems of PCP abuse. PMID- 3086732 TI - Phencyclidine: changing abuse patterns. PMID- 3086734 TI - Neuropsychological assessment of phencyclidine abusers. PMID- 3086733 TI - PCP and crime: just another illicit drug? PMID- 3086735 TI - Phencyclidine intoxication. PMID- 3086736 TI - Diagnosis and treatment of chronic phencyclidine (PCP) abuse. PMID- 3086737 TI - Legal issues associated with PCP abuse--the role of the forensic expert. AB - These cases illustrate some of the complex issues associated with PCP-related litigation. The concept that malice is implied when an experienced drug user commits a crime while under the influence of the drug is not held in most states, at the present time. The authors have now reviewed in detail four cases of unexpected death following the use of neck holds in PCP-intoxicated individuals. In all of the cases, multiple carotid compression holds had been attempted, according to the history. Skin abrasions, hemorrhage into the soft tissues of the neck, and fractures of the hyoid bone and thyroid cartilage provide structural evidence of the application of substantial force to the neck. On autopsy, there has been no evidence of lethal injuries to the bronchial tree, brain, or heart. Drugs related to PCP are known to alter the carotid sinus reflex. Mechanical stimulation of the carotid sinus in the neck normally results in a slowing of heart rate and a decrease in blood pressure. Carotid sinus stimulation, coupled with the effects of PCP on blood vessels, might result in a marked fall in the blood pressure that could lead, ultimately, to death. Individuals intoxicated with PCP may be at a higher risk to complications of carotid compression neck holds. Hence, additional cases would be expected to become medicolegal issues. PMID- 3086738 TI - The long-term effects on neurodevelopment in infants exposed prenatally to PCP. PMID- 3086739 TI - Clinical observations in the treatment of adolescent and young adult PCP abusers. PMID- 3086740 TI - Involvement of dopaminergic, cholinergic, and glutamatergic mechanisms in the actions of phencyclidine-like drugs. PMID- 3086741 TI - Anticonvulsant properties of phencyclidine and ketamine. PMID- 3086743 TI - Cytoimmunotherapy for persistent virus infection reveals a unique clearance pattern from the central nervous system. AB - The mechanism(s) by which infectious or malignant material is cleared by the host has long been an area of intensive study. We have used the murine model of infection with lymphocytic choriomeningitis virus (LCMV) to look at immune clearance during persistent infection. LCMV was selected because the mouse is its natural host, it easily induces acute or persistent infection in vivo, and the mechanism by which it is cleared in vivo during acute infection is now well understood. Clearance, although associated with several antiviral immune effector mechanisms, is primarily dependent on the activity of virus-specific cytotoxic T lymphocytes (CTL) restricted by H-2 molecules of the mouse major histocompatibility complex (MHC). If these cells fail to generate or are depleted, progression from acute to persistent infection occurs. Here, using molecular probes, we show that viral nucleic acid sequences, viral proteins and infectious materials can be efficiently and effectively cleared by adoptive transfer of antiviral H-2-restricted lymphocytes bearing the Lyt 2+ phenotype. Viral materials are cleared from a wide variety of tissues and organs where they normally lodge during persistent infection. Unexpectedly, the mode by which viral materials are removed from the central nervous system (CNS) differed markedly from the mechanism of clearance occurring at other sites. These observations indicate the possible use of adoptive lymphocyte therapy for treatment of persistent infections and suggest that immune clearance of products from the CNS probably occurs by a process distinct from those in other organs. PMID- 3086742 TI - Changing the identity of a transfer RNA. AB - A leucine transfer RNA has been transformed into a serine transfer RNA by changing 12 nucleotides. This result indicates that a limited set of residues determine tRNA identity. PMID- 3086744 TI - Kenyan finds not early Miocene Sivapithecus. PMID- 3086745 TI - Endocast morphology of Hadar hominid AL 162-28. PMID- 3086746 TI - A novel cell surface molecule on early B-lineage cells. AB - B cells and their antibody-secreting progeny represent one of several differentiation pathways that haematopoietic stem cells (HSC) may enter. Cells representing intermediate stages between HSC and B cells have been identified in mammalian haematopoietic tissues and studied intensively over the past decade. This population of early B-lineage cells, termed pre-B, is characterized by cellular proliferation and an orderly cascade of immunoglobulin gene rearrangements, a combination of events leading to the generation of clonally diverse B cells which then migrate to peripheral lymphoid tissues. It remains to be determined what elements determine the polyclonal growth of pre-B cells, how immunoglobulin gene rearrangements are regulated, and what happens to pre-B cells undergoing 'non-productive' immunoglobulin gene rearrangements. These issues could be resolved more easily if early B-lineage cells could be identified precisely and isolated. Here, we describe a cell surface glycoprotein that is selectively expressed by pre-B and newly formed B cells in murine haematopoietic tissues. The molecule, a homodimer formed by disulphide-linked chains of relative molecular mass (Mr) 140,000, is identified by a mouse monoclonal alloantibody called BP-1. PMID- 3086747 TI - Chloroquine and ammonium chloride prevent terminal glycosylation of immunoglobulins in plasma cells without affecting secretion. AB - The generation of an acidic pH in intracellular organelles is required for several membrane and protein recycling processes. For instance, the internalization of ligands by receptor-mediated endocytosis is followed by the development of an acidic pH inside endosomes; this allows dissociation of the ligand, which is then transported to the lysosomes, from the receptor, which is recycled to the cell surface. There is evidence that part of this recycling process involves the distal region of the Golgi complex, where terminal glycosylation occurs: when the plasma membrane transferrin receptor is desialylated by neuraminidase treatment, it acquires new sialic acid molecules after endocytosis and before cell-surface re-expression. Golgi membranes have been shown to contain a proton pump and the distal Golgi cisternae appear to have an acidic content. Here, we have studied the effects of chloroquine and ammonium chloride, which raise the pH of acidic intracellular compartments, on the processing and secretion of immunoglobulins by plasma cells. Sialic acid transfer to terminal galactose residues, a reaction known to occur in the distal Golgi shortly before secretion, is completely and rapidly inhibited in the presence of these drugs, without significant modification of the secretion rate. This effect is accompanied by a dilatation of the Golgi cisternae and is not rapidly reversible. PMID- 3086748 TI - Dual gonadal control of follicle-stimulating hormone. PMID- 3086750 TI - Influences of meningeal cells on brain development. Findings and hypothesis. AB - Destruction of meningeal cells during brain development results in alterations of the extracellular matrix over the surface of the central nervous system, and a regional disruption of the external glial limiting membrane, associated with a reorganization of the glial scaffold. These changes of the glial organization have repercussions on neuronal migration and aggregation leading to a failure of neurons to segregate into spatially separated layers and lobules. We propose that meningeal cells stabilize the labile outer surface of the brain and the glial scaffold during development by specifically controlling the composition of the extracellular matrix at the interface with glial end-feet. PMID- 3086749 TI - Pituitary FSH is released by a heterodimer of the beta-subunits from the two forms of inhibin. AB - Inhibin is a gonadal protein that specifically inhibits the secretion of pituitary follicle-stimulating hormone (FSH). Two forms of inhibin (A and B) have been purified from porcine follicular fluid and characterized as heterodimers of relative molecular mass (Mr) 32,000 (ref. 2). Each inhibin is comprised of an identical alpha-subunit of Mr 18,000 and a distinct but related beta-subunit of Mr 13,800-14,700 linked by interchain disulphide bond(s). Throughout the purification of inhibins, we consistently observed two fractions which stimulated the secretion of pituitary FSH. We report here the isolation of one of the FSH releasing proteins; it has a Mr of 24,000 and its N-terminal sequences up to residue 32 are identical to those of each beta-subunit of inhibins A and B. In the presence of reducing agents, SDS-polyacrylamide gel electrophoresis resolves the FSH-releasing substance into two subunits which are identical in their migration behaviour to the reduced beta-subunits of inhibins A and B. Based on the N-terminal sequence data and Mr of the intact and reduced molecules, we propose that the FSH-releasing substance, which is active in picomolar concentrations, is a heterodimeric protein composed of the two beta-subunits of inhibins A and B linked by interchain disulphide bond(s). The structural organization of the FSH-releasing substance is homologous to that of transforming growth factor-beta (TGF-beta), which also possesses FSH-releasing activity in the same bioassay. We suggest that the substance be called activin to signify the fact that it has opposite biological effects to inhibin. PMID- 3086751 TI - Thermoluminescence dating of loess deposits at Plaidter Hummerich and its implications for the chronology of Neanderthal man. PMID- 3086753 TI - The impact of changes in health care finance on critical care. PMID- 3086752 TI - Reversal of the reserpine-induced ptosis by L-threo-3,4-dihydroxy-phenylserine (L threo-DOPS), a (-)-norepinephrine precursor, and its potentiation by imipramine or nialamide. AB - The effect of L-threo-DOPS on the reserpine-induced ptosis in mice and its modification by imipramine, a norepinephrine (NE) uptake inhibitor, or nialamide, a monoamineoxidase inhibitor, were studied. Intraperitoneal (i.p.) injection of L threo-DOPS (800 mg/kg) significantly reduced the severity of the ptosis. This reversal of the ptosis by L-threo-DOPS was markedly potentiated by i.p. injection of either imipramine (2.5 mg/kg) or nialamide (30 mg/kg). Response to L-threo DOPS was also significantly potentiated by intracerebroventricular (i.c.v.) injection of imipramine (10 micrograms). On the other hand, this treatment with imipramine (10 micrograms, i.c.v.) also significantly potentiated the reversal of the ptosis by NE (20 micrograms, i.c.v.), but the reversal by the subcutaneous (s.c.) injection of NE (1 and 3 mg/kg) was not affected. Reserpine (5 mg/kg, i.p.) markedly decreased the brain content of NE in mice, whereas L-threo-DOPS (400 mg/kg, i.p.) slightly restored it. Moreover, by the pretreatment with nialamide (30 mg/kg, i.p.), L-threo-DOPS produced a significant increase in the brain content of NE in reserpine-treated mice. These results suggested that L threo-DOPS was capable of reversing the reserpine-induced ptosis due to the formation, at least in part of (-)-NE at the synaptic sites of central noradrenergic neurons. PMID- 3086754 TI - [Treatment of advanced prostate carcinoma with a depot form of an LH-RH analog: preliminary endocrinological and clinical results]. PMID- 3086755 TI - [Applicability of laser rays in the treatment of atherosclerotic disorders of the coronary arteries]. PMID- 3086756 TI - [Lupus anticoagulant: an old phenomenon in a new perspective]. PMID- 3086757 TI - [Cost-benefit evaluation of a social psychiatric service]. PMID- 3086759 TI - [Action myoclonias and paranoid alternative psychosis in progressive myoclonic epilepsy (late form of the Lafora type)]. PMID- 3086758 TI - [Organization, effectiveness and cost effectiveness of the complementary management of schizophrenic patients]. PMID- 3086760 TI - Transient syndrome of inappropriate antidiuretic hormone secretion in a patient with infectious mononucleosis and pure red cell aplasia. PMID- 3086761 TI - Profiling of endogenous ligand solutes that bind to serum proteins in sera of patients with uremia. AB - The profiling of endogenous ligand solutes in sera of patients with uremia was performed by using an ultrafiltration device and high-performance liquid chromatography. Seventeen endogenous ligand solutes, which are ultraviolet absorbing substances, were detected in a sample volume of 40 microliters, and four ligand solutes were tentatively identified as indoxylsulfate, hippuric acid, 2-hydroxybenzoylglycine, and 3-indoleacetic acid. One of these ligand solutes designated as peak P was thought to be a candidate for a major drug-binding inhibitor in uremia. PMID- 3086762 TI - Mesangial glomerulonephropathy with decreased circulating C4 and predominant mesangial C4 deposition in association with one null gene at the C4B locus. AB - We report a case of mesangial glomerulonephropathy associated with decreased circulating C4 in a young man with recurrent microscopic hematuria and one null gene at the C4B locus. Mesangial deposits moderately reactive with anti-C4 and weakly reactive with anti-C3 and anti-IgA were found on renal biopsy. No evidence was found to support a diagnosis of IgA nephropathy or any other of the recently described mesangial glomerulonephropathies with immunoglobulin and complement deposition. This case apparently represents a unique, heretofore undescribed variant of mesangial glomerulonephropathy associated with mesangial C4 deposition and C4 hypocomplementemia. PMID- 3086763 TI - Behavioral evaluation of perinatal PCB exposure in rhesus monkeys: fixed-interval performance and reinforcement-omission. AB - Two experiments were conducted to examine the prolonged behavioral effects of perinatal exposure to polychlorinated biphenyls (PCBs, Aroclor 1248) in rhesus monkeys. Experiment I involved testing a group of three monkeys whose mothers had been fed 2.5 ppm PCBs in their diets both before and throughout gestation and nursing (concurrent exposure condition), and a group of three control monkeys whose mothers had received no added dietary PCBs. These offspring began testing at approximately 60 months of age. In experiment II the same group of female breeders which were fed PCBs in experiment I underwent a second round of breeding after being off the contaminated diet for an average of 20 months (postexposure condition). Additionally, another group of female monkeys underwent breeding while receiving concurrent exposure to 0.5 ppm PCBs in their diet. Control female monkeys received no added dietary PCBs. Four offspring from the 2.5 ppm postexposure condition, four from the 0.5 ppm concurrent exposure condition and five control offspring survived to begin testing here at approximately 40 months of age. All monkeys from experiments I and II were tested under a series of fixed interval schedules of food reinforcement consisting of FI 30 sec (10 sessions) and FI 60, 300 and 600 sec (15 sessions each). Performance measures included overall response rate, index of curvature (IC) and postreinforcement pause (PRP). There were no consistent differences in FI performance between PCB and respective control groups except for a slightly though significantly lower IC in the PCB groups of experiment II under FI 300 and 600.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086764 TI - [Evaluation of the activity of various lysosomal enzymes in the cerebrospinal fluid and blood in cases of brain concussion]. AB - The results of determinations of lysosomal enzymes: mannosidase, b-galactosidase and b-glucosidase, in the cerebrospinal fluid and blood are presented in 72 patients with severe brain trauma. The determinations were carried out at different times after the trauma. The study demonstrated a significantly lower level and in a smaller degree expressed variability of enzymes in the cerebrospinal fluid in relation to blood. It seems that the level of b glucosidase in the cerebrospinal fluid depends on the level of this enzyme in the blood, while no such evident correlation was found for the remaining enzymes. PMID- 3086766 TI - Occurrence and distribution of 5-S-cysteinyl derivatives of dopamine, dopa and dopac in the brains of eight mammalian species. AB - The 5-S-cysteinyl derivatives of dopamine, dopa (3,4-dihydroxyphenylalanine) and dopac (3,4-dihydroxyphenylacetic acid) were synthesized and used as reference compounds in high performance liquid chromatography analyses of extracts from various brain regions of eight mammalian species. All three metabolites were detected in the brains of all the species studied. The regional distribution of the metabolites was similar to that of dopamine; the metabolite concentrations ranged from less than 0.1 percent to more than 1 percent of the dopamine level, the highest ratios generally being found in substantia nigra. It is suggested that the 5-S-cysteinyl catechol metabolites have been formed after autoxidation of catechols to quinones and subsequent coupling to glutathione. The adduct thus formed is finally split by peptidases to yield the 5-S-cysteinyl derivatives. PMID- 3086765 TI - Interactions of testosterone and short-photoperiod exposure on the neuroendocrine axis of the male Syrian hamster. AB - Exposure of adult male golden hamsters to short days (less than 12.5 h light/day) leads to suppression of gonadal function which is secondary to reductions in gonadotropin and prolactin (PRL) secretion. Short-day (SD) exposure also leads to a reduction in hypothalamic norepinephrine (NE) and dopamine (DA) metabolism and an increase in hypothalamic LHRH content which appears to be related to a decrease in LHRH release. To determine whether SD-induced changes in NE and DA metabolism are dependent or independent of changes in circulating testosterone (T) levels and thus possible mediators of photoperiod effects on gonadotropin secretion, the effects of castration and steroid replacement on hypothalamic amine metabolism were studied in male hamsters maintained under long or short photoperiod conditions. The presence of Silastic T-implants resulted in a greater suppression of LH and FSH in SD than in long-day (LD) hamster, but increased median eminence (ME) LHRH content in both groups. Exposure of castrate hamsters to short days led to a reduction of NE turnover in the ME and medial preoptic suprachiasmatic area (MPOA) and a decrease in serum FSH levels. LH levels tended to be lower, but not significantly so. The decrease in ME NE turnover was potentiated by T replacement, but in the MPOA-SCN, T-implants reversed the effects of short days. NE turnover in the MBH was reduced by T in both LD and SD animals, but the effect was much greater in the SD animals. SD exposure also caused a decrease in ME DA metabolism that was reversed by T replacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086767 TI - Intracranial hemorrhage in patients with hemophilia. AB - Intracranial hemorrhage (ICH) is a life-threatening complication of hemophilia. Seven of the 288 hemophiliacs living in Israel suffered eight episodes of ICH during the years 1972 to 1982. All episodes occurred in hemophilia A patients, with a higher incidence among patients with factor VIII inhibitor. Diagnosis was confirmed by computed tomographic scan in seven of the eight episodes. Four of the 7 patients died despite adequate factor replacement and supportive therapy, probably due to a conservative and hesitant neurosurgical approach. The correction of factor VIII to hemostatic level alone is inadequate in the majority of cases, and there is sudden deterioration in the patient's condition and death. Operation is strongly recommended when no improvement is noted within a few hours. PMID- 3086768 TI - Mycobacterium tuberculosis meningitis: a report of twelve cases and a literature review. AB - Twelve recent cases of Mycobacterium tuberculosis meningitis were presented, and the literature was reviewed. There are no particularly new or unique therapies or approaches to the management of this most serious disease. The major obstacle to successful diagnosis and treatment of tuberculous meningitis continues to be a lack of clinical suspicion of its presence. As illustrated in the cases presented, it has been our experience that patients already moribund or nonresponsive do not respond, regardless of the intervention undertaken. The most sensitive and economical method of detecting M. tuberculosis in the CSF may be LPA. However, this has not yet been widely validated or accepted. Larger volumes of CSF should be sent to the laboratory for testing and centifuged to about 5x concentrations before both acid-fast bacilli staining and culture are attempted. If tuberculous meningitis is suspected, three-drug therapy can be started immediately without jeopardizing subsequent culture confirmation of the presence of the TB bacillus. In addition, these patients must be followed closely to detect hydrocephalus at the earliest possible moment. When patients fail to respond to appropriate antituberculosis and pressure-reducing therapy, hydrocephalus should be actively sought by either CT or radioisotope cisternography. Although the decision to proceed to ventricular drainage or shunting must be individually made in adult patients with infection-related hydrocephalus, we agree with others that surgical intervention should be considered early and should be performed if the level of consciousness deteriorates, intracranial pressure increases, or ventricular enlargement or enhancing basal exudates are identified on CT. PMID- 3086769 TI - Free light chains in neurologic diseases: first reports. PMID- 3086770 TI - The need for consultation/liaison psychiatry services in military hospitals. PMID- 3086771 TI - An insect bioassay as a primary screen for nerve agent antidotes. PMID- 3086772 TI - Accuracy of pre-induction audiograms. PMID- 3086773 TI - The emergence of a medical school: impact on laboratory utilization and cost containment efforts in an affiliated teaching hospital. PMID- 3086774 TI - Heart function studies in dogs after acute gamma irradiation of the precordium. PMID- 3086775 TI - Management of stab wounds to the abdomen. PMID- 3086776 TI - Thoracentesis using the Husted needle and loss of resistance technique: report of a technique. PMID- 3086777 TI - Bipolar disorder in post-traumatic stress disorder--a difficult diagnosis: case reports. PMID- 3086778 TI - Bronchial washings in the diagnosis of pulmonary tuberculosis. PMID- 3086779 TI - Hirschsprung's disease: parental rejection of treatment. PMID- 3086781 TI - Behaviorally conditioned suppression of mitogen-induced lymphoproliferation and antibody production in mice. AB - Conditioned immunosuppression was induced in C57BL/6 mice by pairing saccharin drinking (conditioned stimulus) with an i.p. injection of 250 mg/kg cyclophosphamide (unconditioned stimulus). Conditioned mice showed depressed mitogen-induced lymphoproliferation. This depression was significant for T-cell- but not for B-cell--proliferation. Mice also exhibited depressed antibody production against sheep red blood cells until 15 days after immunization. The kinetics of serum antibody levels suggest that conditioning amplifies the immunosuppressive effects of cyclophosphamide. Furthermore, we show in this report that a depression of cellular and humoral components of the immune system can be observed when conditioning is performed after immunization, the latter being not paired with the conditioned stimulus. PMID- 3086780 TI - Interferon-alpha, beta and -gamma induce (2'-5') oligoadenylate synthetase in cultured mouse brain cells. AB - Basal and interferon (IFN)-induced levels of (2'-5') oligoadenylate synthetase activity were measured in astrocyte cultures from the mouse cerebral cortex, in neurone-enriched and mixed cerebellar cultures, and in two continuous neural cell lines by a radioimmunoassay procedure. All untreated cultures contained measureable enzyme activity. Both purified IFN-alpha, beta and recombinant IFN gamma induced the enzyme in all cultures with the exception of the C8S cell line which did not respond to IFN-gamma. IFN-alpha, beta was more effective than IFN gamma. The amplitude of induction by IFN-alpha, beta was highest in the cell lines, intermediate in cortical astrocytes and lowest in mixed and neurone enriched cultures from the cerebellum. PMID- 3086782 TI - Keying in on the business of graduate education in nursing. PMID- 3086784 TI - Non-Meckelian diverticulosis of the jejunum and ileum: a report of four cases, one with an arteriovenous malformation. PMID- 3086783 TI - Carbaryl. A toxicological review and risk analysis. PMID- 3086785 TI - Microbiological hazards in laboratories can be controlled. PMID- 3086786 TI - [Clinical features of complicated experimental uveitis caused by enteroviruses in monkeys]. PMID- 3086787 TI - An unusual case of Bence Jones myeloma with extremely low levels of monoclonal immunoglobulin. AB - This report describes the case of a 64-year-old woman with painful symptoms of the mandible produced by a lesion diagnosed as Bence Jones myeloma (kappa type). A bone survey revealed osteolytic lesions in the mandible, cranial bones, and humerus. Urinalysis showed no abnormality regarding the presence of monoclonal immunoglobulin fragments. Serum analysis by electrophoresis and immunoelectrophoresis did not demonstrate the presence of monoclonal immunoglobulin. However, the latter procedure disclosed a precipitation line formed by concentrated urine against anti-kappa serum. Microscopic examination of a mandibular specimen revealed numerous atypical plasma cells. Immunoperoxidase studies demonstrated kappa-chains localized within the rough endoplasmic reticulum, perinuclear region, and Golgi apparatus of the myeloma cells. The pathogenetic mechanism of the condition in this case, as well as its relation to Bence Jones myeloma and nonsecretory myeloma, is discussed. PMID- 3086789 TI - Medical liability: no magic bullets for malpractice. PMID- 3086788 TI - Variability of the styloid process and stylohyoid ligament in panoramic radiographs. AB - This article deals with the incidence of anatomic variations in the styloid process and stylohyoid ligament as found in panoramic radiographs. Also, the accuracy was determined for measuring the length of styloid processes from panoramic radiographs, the variation in length of the styloid process with age, and the relationship of elongated styloid processes and ossified stylohyoid ligaments to symptoms of styloid-stylohyoid syndrome. Variations in styloid process and stylohyoid ligaments are not uncommon, especially segmentation of the process in young subjects. The apparent length of the styloid process was magnified approximately 1.37 times and was never diminished by panoramic radiographs. A steady increase in styloid process length was observed to age 30 years, with another slight increase starting at age 60 years. Subjects with elongated styloid processes (greater than 40 mm) had the highest incidence of discomfort on swallowing, whereas subjects with ossification of the stylohyoid ligament had the highest incidence of discomfort on turning the head from side to side. PMID- 3086790 TI - Clinician-interactive computerized utilization review for mental health care. PMID- 3086791 TI - Specialized beds program: diversification options in skilled nursing facilities. AB - Serving patients in the SNF who need specialized, highly skilled care demands strong commitment, intensive planning, cooperative research, and continuous reassessment and evaluation. Specialty care programs are necessary to provide viable alternatives to acute care hospitalization for patients who need long term care. Health care organizations should continue their cooperative efforts to ensure the appropriate and cost effective use of services. Based on CCM's successful history of operating special care programs, providers should be encouraged to become leaders in developing specialized care alternatives. The appropriate use of long term care as well as acute care settings is in the best interest of patients, communities, and the health care industry itself. PMID- 3086792 TI - A comprehensive bereavement program. AB - This case study illustrates how one woman was able to take advantage of a variety of hospice bereavement services. In addition to attending monthly social support group meetings and six therapeutic support group sessions, Lillian received 12 home visits or approximately 18 hours of individual support. Not all hospice survivors became so intensely involved in the follow-up services programs offered by Hilltop Hospice. During the five-year period, 1980-1984, approximately 80% of the hospice survivors, or 200 clients, received some form of direct bereavement services; most of the others were provided with supportive correspondence throughout their first year of bereavement. Although approximately 10% of the hospice survivors became involved in the social and the therapeutic support groups, in addition to receiving individual support, most survivors found the individual support services to be sufficient. However, in hospice programs where resources are limited and not all survivors can be assigned a volunteer, support groups can be designed to compensate for a lack of available volunteers. A comprehensive hospice bereavement program takes into account not only the varying resources of the hospice but the individual characteristics of survivors as well. Because clients' grief experiences differ, as well as their personalities, coping styles, and circumstances, a hospice should be prepared to offer a variety of bereavement services. In addition, surviving family members may be more likely to accept follow-up support from the hospice team if they can choose a particular service to meet their individual needs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086793 TI - Considerations of hospital viability in rural Texas. AB - The rural hospitals in Texas face the same situation as rural hospitals throughout the country. Unfortunately, little data are available to define the scope or possible duration of the problem. However, rural hospital administrators currently believe that their facilities are being hurt by increased government regulation and that today's figures on average daily census indicate that the problem could threaten their hospital's long-term viability. Initial investigations have shown that the problem of casualty is a complex one; multiple factors interact to exacerbate the situation, such as more stringent enforcement of Medicare certification standards, review of claims and quality of care by PROs, and the use of PPS. Other factors cited include the economic recession, the exodus of young people from rural areas to urban areas, the high cost of technology, and the preadmission review by insurance companies. A study that will both sample and survey rural hospital viability using financial ratio analysis and service utilization data is presently being undertaken to provide some responses to these concerns. Further, it will later examine how rural hospital administrators are responding to the problem of decreased hospital viability. It is possible that new coping strategies may be developed from the study results that will change present modes of health care delivery and result in regional networks and more diversified health care services. PMID- 3086794 TI - Institutional review boards and quality. PMID- 3086795 TI - Reimbursement policy for long term care. PMID- 3086796 TI - The quality assurance project at the King's Fund Centre in London. PMID- 3086797 TI - General report and commentary: the realities of quality assurance. PMID- 3086798 TI - [Meningoencephalitis caused by Mycoplasma pneumoniae]. PMID- 3086799 TI - What should medical students learn about otolaryngology-head and neck surgery. PMID- 3086800 TI - A speech-to-noise ratio test with the bone-anchored hearing aid: a comparative study. AB - Hitherto, for persons with impaired hearing who cannot use an air conduction hearing aid, the only alternative has been a conventional spring-loaded bone conduction hearing aid. Now, with minor surgery, a titanium screw can be implanted in the bone behind the ear and a coupling, which penetrates the skin, can be attached, giving a new kind of hearing aid--the "bone-anchored hearing aid." Improved quality of sound is one of the patients' subjective assessments. Improvement was not confirmed by a standard speech-discrimination test. With new speech material consisting of sentences in noise, the speech-to-noise ration (SN) has been determined for 24 patients. Patients who previously used a conventional bone conduction hearing aid improved their SN on the average by 3.3 dB. The most important difference between the two aids related to improved SN is probably the increased audibility between 600 and 6000 Hz. PMID- 3086801 TI - Diagnosis and treatment of perilymph fistulas without hearing loss. AB - In 1978, I reported on the diagnostic criteria and therapy based on the treatment of 34 cases of perilymph fistula. Of that group, 20 patients had no hearing loss associated with the fistula. Since that time, an additional 30 cases of fistula- 15 without hearing loss--have been seen and treated operatively. The 30 significant variables of history and physical findings identified in the first study were statistically reviewed, along with a new finding that seems highly significant. Twenty-three of the 26 new cases so evaluated had a positive "eyes closed turning test" (staggering when turning to the side of the lesion after walking with eyes closed). A further finding has been the presence of an abnormally placed round window membrane, in most cases involving the round window. The total operative population of fistulas, both those with and without hearing loss, is reviewed to identify the operative technique best suited for each window and the graft material most likely to succeed. Perichondrium is the choice tissue for graft material, except for very small fistulas at the annular ligament. The graft must be held firmly in place, with either a prosthesis or appropriate packing, carefully avoiding adhesions between the round window and the tympanic membrane. PMID- 3086802 TI - Regenerated middle ear mucosa after tympanoplasty. Part II. Scanning electron microscopy. AB - The ultrastructural appearance of the regenerated middle ear epithelium, found at the second operation of staged ICWT with mastoidectomy, has been investigated herein with the scanning electron microscope. The regenerated epithelium consists of flat nonciliated cells, "elevated" nonciliated cells with microvilli, and ciliated cells. Secretory material is present on the surface of the "elevated" nonciliated cells surrounding the ciliated ones. Regeneration of the mucosa occurs following precise topographic differences that mimic the distribution of epithelial cells in the normal middle ear. It is confirmed that a morphologically normal middle ear epithelium regenerates to cover all denuded bone surfaces within 12 months--after first stage ICWT with mastoidectomy--when silicone rubber sheeting has been used to maintain an aerated middle ear and mastoid space. PMID- 3086803 TI - Computed tomography in the diagnosis of cochlear otosclerosis. AB - Twelve patients with surgically proven otosclerosis and sensorineural hearing loss were studied with high-resolution computed tomography (CT). The purpose was to identify abnormal bony changes that could be diagnostic of cochlear otosclerosis. Of the 24 temporal bones thus studied, 10 showed positive findings. The findings in our study--as well as those of others--show a pericochlear zone of radiolucency. The precise origin of this is undetermined. PMID- 3086804 TI - Middle ear semipermeable membrane tubes for prolonged retention. AB - Our 1981 prospective study confirmed the success of semipermeable membrane tubes in ventilation of middle ears, while protecting them from moisture when the patients bathed or swam. That study employed modern membrane tubes, with membrane pore size 2.5 to 5 times greater than tubes used in early studies with less favorable outcomes. Currently, 21 patients with effusion had placement of a Donaldson design (Xomed, Inc., Jacksonville, Fla.) membrane tube in one ear and the new T-grommet membrane tube in the second ear. The T-grommet membrane tube is found to outlast the Donaldson design tube significantly. We recommend Donaldson membrane tubes for patients having tubes placed for the first time. For subsequent procedures, we employ T-grommet membrane tubes. We also use the T grommet membrane tube for adults with chronic eustachian tube problems. Both tubes continue to show a low incidence of complications and draw highest praise from patients for their water-resistant capabilities. PMID- 3086805 TI - The effect of nuclear magnetic resonance imaging on metallic middle ear prostheses. AB - Nuclear magnetic resonance imaging, a relatively new diagnostic instrument, is a noninvasive imaging method which, among its many advantages, uses no ionizing radiation. There are a few limitations and contraindications to its use. There may be displacement of intracerebral aneurysm clips and metallic implants, and cardiac pacemakers can be disabled because of the high magnetic field created by this device. We studied the effects of a magnetic field on metallic middle ear prosthetics and concluded that nuclear magnetic resonance imaging should offer no risks to hearing or otologic function in patients with nonferromagnetic metallic middle ear prosthetics. Nuclear magnetic resonance imaging is contraindicated in patients with cochlear implants. PMID- 3086806 TI - Experience with tracheal resection for traumatic tracheal stenosis. AB - Ten patients with traumatic tracheal stenosis--unresponsive to conservative therapy--underwent tracheal resection. Two of the stenoses resulted from gunshot injuries, three were due to prolonged intubation, and five developed after tracheotomy. Eight of the operations were completely successful. There was one death, and one patient has had recurrent granulation tissue at the anastomotic site. The pathogenesis of tracheal stenosis, as well as its treatment--including the technical details of tracheal resection--are discussed. PMID- 3086807 TI - Topographic analysis of Horner's syndrome. AB - Horner's syndrome or oculosympathetic paralysis is not an uncommon finding in patients with head and neck neoplasms. While in most cases the syndrome is easily established at the bedside, it can be confirmed and topographically defined as a central, preganglionic, or postganglionic lesion through sequential pharmacologic testing. The importance of such localization lies in differentiating neoplasia vs. a benign condition as the cause of the syndrome. Such variants as congenital Horner's, an alternating Horner's, and a pseudo-Horner's syndrome are discussed in regard to their differential features. PMID- 3086808 TI - Ototoxicity of cisplatin vs. platinum analogs CBDCA (JM-8) and CHIP (JM-9). AB - Cis-diamminedichloroplatinum (cisplatin), a divalent platinum compound and cell cycle nonspecific chemotherapeutic agent, produces a permanent high-frequency sensorineural hearing loss and a dose-related cumulative renal insufficiency with tubular necrosis and interstitial nephritis. Synthetic platinum analogs are presently being tested to identify an analog with greater antitumor activity, but less ototoxicity and nephrotoxicity than cisplatin. The objectives of this study were to analyze the potential cochlear and nephrotoxic effects of two synthetic platinum analogs presently in phases I and II of clinical trials, CBDCA [JM-8 or cis-diammine, 1,1-cyclobutane dicarboxylato (2)-0,0(1)-platinum (NSC-241240)] and CHIP [JM-9 or cis-dichloro-trans-dihydroxybisisopropylamine platinum IV (NSC 256927)]. Cytocochleography, auditory brain-stem evoked response (ABR), double blind light microscopy of renal tissues, and gamma emission analysis of 195mpt localization in viscera and inner ear were employed in the evaluation of cisplatin and platinum analogs (JM-8 and JM-9) in adult guinea pigs. Final results indicate that the investigational chemotherapeutic analogs CBDCA (JM-8) and CHIP (JM-9) do not produce the ototoxicity and nephrotoxicity characteristic of cisplatin. Furthermore, these findings demonstrate 195mpt localization in the vestibular labyrinth and confirm previous platinum distribution studies in the organ of Corti and stria vascularis tissues. PMID- 3086809 TI - Allergic rhinitis--update. AB - More than 20% of the general population is afflicted with a common medical disorder--allergic rhinitis. Recent research in rhinitis has brought about much new information and created possibilities for new means and methods of diagnosis and treatment. PMID- 3086810 TI - Relief of upper airway obstruction by adenotonsillectomy. AB - Adenotonsillectomy is often performed to relieve upper airway obstruction, even in children who do not present with severe apnea. Although adenotonsillectomy provides dramatic relief from obstructive sleep apnea, little evidence is available as to the efficacy of surgery in the far more prevalent cases of partial airway obstruction. We report the results of a prospective study of 100 children with adenotonsillar obstruction (without severe apnea) and 50 age matched control children. The majority of patients exhibited appreciable sleep disturbances preoperatively, as compared to controls, and had substantial postoperative improvement, as demonstrated by parental questionnaire and sleep sonography--the computer-aided analysis of respiratory sounds. Mouth breathing and behavior problems were also prevalent preoperatively and were affected positively by adenotonsillectomy. It appears that surgery in such cases can have far-ranging benefits, even for the child whose obstruction does not demonstrate severe apnea. PMID- 3086811 TI - Internal carotid artery epistaxis. AB - Epistaxis from the internal carotid artery (ICA) or bleeding from the ICA at the skull base is a rare, frightening, and difficult management problem. We present five cases, with a variety of causes--in all of which the patients survived massive hemorrhage--and suggest a protocol for management of the condition. PMID- 3086812 TI - Aspiration and nasogastric intubation. AB - Routine use of nasogastric tubes in major surgery is associated with unwarranted risks of aspiration through at least three mechanisms: hypersalivation--allowing pooling of secretions in the hypopharynx, a depressed cough reflex, which is often associated with nasogastric intubation, and various laryngeal and pharyngeal abnormalities that are frequently caused by nasogastric tubes, leading to an inability to handle secretions and protect the airway. Using indirect cinelaryngoscopy, we can accurately document these mechanisms; three representative cases are presented here. Aspiration associated with nasogastric intubation is a newly described but potentially serious complication. Routine use of nasogastric intubation should be abandoned, except when the clinical situation warrants it. PMID- 3086813 TI - Principles and hazards of electrocautery in otolaryngology. AB - Electrocautery is used extensively in otolaryngology--head and neck surgery. Its commonplace use and excellent safety record may lull the surgeon from heeding the device's potential dangers. User error causes the majority of patient injuries. A thorough understanding of the electrophysical principles and hazards is essential for even the occasional user. Three cases of electrosurgical injury are reported to demonstrate problem areas in electrocautery usage. The basic electrophysical properties are described, and guidelines for prevention of injury to the patient are reviewed. PMID- 3086814 TI - Complications of hyperbaric oxygen in the treatment of head and neck disease. AB - Hyperbaric oxygen has been advocated in the treatment of many head and neck diseases. Reports of such treatments have described eustachian tube dysfunction as the only complication. A review of patients receiving hyperbaric oxygen for head and neck diseases at The Mount Sinai Medical Center revealed serious complications, which included seizure, stroke, and myocardial infarction. In addition, follow-up study of these patients demonstrated that 11 patients treated for radiation-induced necrosis had an undiagnosed recurrence of cancer. PMID- 3086816 TI - Stapedectomy for the home temporal bone dissection laboratory. AB - During the last 15 years, there has been a steady decline in the number of stapedectomies performed. Suggestions have been made to limit the residents' training in stapes surgery as well as to determine who is qualified to perform stapedectomies. It is well recognized that the skills and precision required for a stapedectomy are different from those used in chronic ear surgery and, if these precise techniques are not used on a regular basis, one will lose the dexterity required for this operation. A technique has been developed that enables the resident or infrequent operator to improve his skills with stapedectomy in the laboratory, prior to being confronted with a patient. It should help to improve the residents' surgical experience as well as maintain the surgical skills required for this operation. PMID- 3086815 TI - Steroid hormone receptors in laryngeal carcinoma. AB - The larynx has long been shown to be a target organ for androgenic steroids in both women and men, and specific androgen receptors have been determined in normal laryngeal mucosa and in laryngeal carcinoma tissue. In this study, samples from 21 primary laryngeal carcinomas, from 4 recurrent laryngeal carcinomas and from 1 cervical metastasis of laryngeal carcinoma were obtained at the time of surgery to assay specific androgen, estrogen, and progesterone receptors. Specific androgen receptors were found in 8 samples (31%). The level of receptors varied from 1.7 femtomoles (fmol) per milligram to 7.3 fmol/mg cytosol protein. Detectable levels of specific estrogen receptors were found in 18 samples (69%) and progesterone receptors in 8 of the 15 samples studied (53%). There was no apparent correspondence with donors' sex, since samples from both females and males contained all kinds of receptors. We know that antiestrogen inhibits the growth of squamous carcinoma cells lines positive for estrogen receptors in vitro and that this effect is reversible with the appropriate hormone. Thus, the relatively high percentage of estrogen and progesterone receptors found in laryngeal carcinoma tissue may open new aspects in the treatment of laryngeal carcinoma with antihormones. PMID- 3086817 TI - Implementing the ANSI Z 136.3 laser safety standard in the medical environment. AB - The American National Standards Institute (ANSI) is an organization comprising several committees of expert volunteers who have traditionally determined the industry consensus standards in various fields. The existing federal legislation and the suggested state laser-safety regulation are based on the 1980 ANSI Standard, "For the Safe Use of Lasers." It was quickly recognized that the safety needs of the industrial and medical environments differed sufficiently to prompt the American National Standards Institute to form a committee to write a new set of standards for "Laser Safety in the Health Care Environment" (ANSI Z 136.3). This standard will apply not only to hospitals but also to offices, clinics, and anywhere else that the laser is used for medical purposes. This paper will outline this important laser-safety standard and describe in detail how best to implement it in the environment in which the otolaryngologist--head and neck surgeon practices. PMID- 3086818 TI - Neuro-Trace: a new intraoperative nerve stimulator. PMID- 3086819 TI - Antibodies to the glutamate dehydrogenase of Plasmodium falciparum. AB - Polyclonal antisera raised against Plasmodium knowlesi reacted with NADP-specific glutamate dehydrogenase (GLDH) of P. knowlesi, GLDH of P. falciparum and GLDH of Proteus spp. The antisera did not react with NAD(P) GLDH from bovine liver. Polyclonal antisera raised against the GLDH of Proteus spp. cross-reacted with GLDH from P. falciparum. Monoclonal antibodies (McAbs) obtained from mice immunized with Proteus GLDH were either specific for the bacterial enzyme or cross-reacted with P. falciparum GLDH. The selected McAbs did not react with GLDH from P. knowlesi, P. chabaudi or P. berghei. The GLDH of P. falciparum was shown to be a cytosolic protein (by FAT) with a subunit molecular weight of approximately 49 000 Da (by immunoprecipitation) having a predominantly hexameric form (by sucrose density gradient). Implications of the conserved sequences of GLDHs and other enzymes are discussed. PMID- 3086820 TI - Killing of schistosomula of Schistosoma mansoni by macrophages: induction by T cell clone-derived lymphokines and interferon-gamma. AB - The induction of schistosomulicidal activity of peritoneal macrophages by concanavalin A-stimulated supernatants from long-term T-cell clones and by interferon-gamma (IFN-gamma) was investigated in detail. Optimal conditions of in vitro macrophage activation by T-cell clone supernatants were established. Macrophages from 13-week S. mansoni-infected mice responded to lymphokine activation as well as resident macrophages from uninfected mice. IFN-gamma was shown to play an essential role in induction of schistosomulicidal macrophage activity: recombinant IFN-gamma at high concentration could induce schistosomula killing, and an anti-IFN-gamma antiserum inhibited the induction of schistosomulicidal activity by T-cell clone supernatants. Our data also indicate that macrophage activation could be obtained by IFN-gamma in synergy with other lymphokines in the supernatant of long-term T-cell clones. Macrophages from mice injected with T-cell clone supernatants were primed in vivo and triggered to kill schistosomula in vitro in the presence of lipopolysaccharide (LPS). The data demonstrate that lymphokines produced by T-cell clones and, in particular, IFN gamma can participate in the activation of schistosomulicidal macrophages. PMID- 3086821 TI - Schistosoma mansoni: an ultrastructural examination of pulmonary migration. AB - The migration of schistosomula through the lungs of mice has been investigated at the ultrastructural level. On Days 4 and 7 post-infection schistosomula were located only within the vasculature. Newly arrived Day 4 schistosomula were highly convoluted and completely occluded vessels measuring approximately 15-25 micron in diameter. By Day 7 parasites were located in pulmonary capillaries, often causing considerable distension. The subtegumentary fibrous interstitial layer was absent in elongated lung schistosomula. The minimum diameter of such parasites was 8 micron, and their tegument was usually unridged and flattened against the vascular endothelium, thus resulting in close apposition of endothelial and tegumental membranes. The tight fit of schistosomula in the pulmonary capillaries implies that migration through them is both a strenuous and slow process. The migratory delay in the lungs after arrival from the skin occurs because dimensional changes are necessary for successful capillary migration. PMID- 3086822 TI - [Biorhythmologic analysis of the effect of alcohol on human acid-base balance and blood gas composition]. PMID- 3086823 TI - Gastrin in the mechanisms of genetic determination of feeding behavior in rabbits. AB - Spreading of a dominant motivation to the molecular intracellular mechanisms of genetic memory was studied. Blockage of protein synthesis in the nervous system selectively abolishes food motivation in rabbits during stimulation of the lateral hypothalamus but exerts no noticeable effect on avoidance responses during stimulation of the ventromedial hypothalamus. During protein synthesis blockage, food motivation returns to normal upon pentagastrin intracerebroventricular (i.c.v.) injection. Intracerebroventricular administration of antigastrin immunoglobulin inhibits feeding reaction to lateral hypothalamic stimulation but not avoidance response to ventromedial hypothalamic stimulation. It was concluded that feeding motivation translates into feeding behavior in the following stages: motivational excitation, gene activation, mRNA synthesis, formation of a gastrin-like peptide, and expression of feeding behavior. PMID- 3086824 TI - Effect of endotracheal continuous positive airway pressure on sensitivity to carbon dioxide and on respiratory timing in preterm infants. AB - To determine the effects of continuous positive airway pressure (CPAP) on ventilatory response to CO2 and inspiratory and expiratory duration in preterm infants, 24 preterm infants with an average birth weight of 1220 g were studied at a mean age of 10.6 days. CPAP was applied via an uncuffed endotracheal tube. Testings were performed between ambient pressure and a positive airway pressure of 10 cm H2O. Approximately 2/3 of the applied pressure was transmitted to the esophagus. All infants demonstrated a ventilatory response to carbon dioxide of less than 50 ml/min per mm Hg Pco2 at ambient pressure, and no infant showed significant improvement at increasing levels of CPAP. Drive to breathe, as reflected in the inspiratory flow rate (Vt/Ti) also failed to change significantly. It may be concluded that in the apparent absence of significant changes in lung volume, CPAP fails to increase sensitivity to CO2 in preterm infants recovering from hyaline membrane disease. PMID- 3086825 TI - Oxygen and resolution of lung injury. AB - We investigated the effects of varying inspired oxygen concentrations on the resolution of oleic acid-induced lung injury in rabbits. Rabbits were injected intravenously with oleic acid and maintained in room air, or exposed to 60, 70, or 80% oxygen for periods of 7 or 10 days. Oleic acid caused hemorrhagic pulmonary edema with hypoxemia. Hypoxemia was more profound in the oxygen-treated animals, a difference that was significant after 7 days' exposure to 60 and 70% oxygen, and after 4 days to 80% oxygen. Mortality was increased in the animals maintained in 80% oxygen. The data suggest that environmental oxygen concentrations greater than 60% interfere with the return to normal lung function following oleic acid injury in rabbits. The hypoxemia may be due to either mismatching of ventilation and perfusion or to a diffusion block resulting from the increased septal width. There was no evidence of massive pulmonary edema as a cause of the hypoxemia. It was not possible to distinguish between injury primarily caused by oxygen and its interference with the healing process. PMID- 3086826 TI - Ventilatory response to increased dead spaces in the first week of life. AB - We have developed a method for quantitatively assessing respiratory control in a group of 10 full-term healthy babies, mean age at test 5 days, by measuring their ventilatory response to added external dead spaces. The dead spaces were equal to 0.5, 1, 2, and 3 anatomic dead spaces (2.2 ml/kg body weight), respectively. Tidal volumes were measured by a nasal mask and a 200-I rigid container. End tidal CO2 was monitored via a tube in the nostril by a mass spectrometer. Baseline measurements were made during a 10-minute period, after which similar recordings were obtained with each of the dead space tubes. The system was calibrated against a 20-ml syringe. The mean baseline ventilation was 602 ml/minute. On the addition of 0.5, 1, 2, and 3 dead spaces, minute ventilations were increased by 37.5, 74.7, 150.7, and 273.6%, respectively. These increases were due to rises in tidal volume rather than respiratory rate. End-tidal CO2 rose by 1.8 and 4 mmHg on the addition of 2 and 3 dead spaces. When the results were compared with expected minute ventilations--based on the baseline recordings and corrected for the added dead spaces and for changes in anatomic dead space ventilation due to alterations in respiratory rate--the results were within 10% of expected values. PMID- 3086827 TI - An analysis of the variability in estimates of bioenergetic variables in preterm infants. AB - Estimates of average daily energy expenditure and minimal observed oxygen consumption are commonly used to characterize the energy metabolism of neonates. Yet, the errors inherent in these estimates have not been defined. Using measurements of oxygen consumption and carbon dioxide production made in healthy growing low birth weight infants during eight consecutive 3-h interfeeding epochs, we have determined the variability in the mean oxygen consumption, carbon dioxide production, respiratory quotient, total daily energy expenditure, and the minimal observed oxygen consumption among the feeding epochs. The coefficient of variation for oxygen consumption ranged from 3.1 to 9.1%, for minimal observed oxygen consumption from 3.7 to 16.7%, for carbon dioxide production from 3.3 to 7.4%, and for total daily energy expenditure from 2.9 to 7.6%. The SDs for respiratory quotient ranged from 0.008 to 0.066. From these 24-h data we have calculated the error in predicting daily estimates of the mean values for these variables if observations are made for less than 24 h. As expected, this error decreases with increasing duration of observation. These data should prove useful in the design and interpretation of investigations of neonatal energy expenditure. PMID- 3086828 TI - Alteration of the N-formyl-methionyl-leucyl-phenylalanine-induced response in cystic fibrosis neutrophils. AB - In order to determine whether cystic fibrosis neutrophils are affected in their secretory functions, lysosomal enzyme release and chemiluminescence (light emission from cells) were assayed in patients' cells and compared with those in normal control cells. We observed a decreased response of cystic fibrosis neutrophils in beta-glucuronidase release and chemiluminescence after stimulation by N-formyl-methionyl-leucyl-phenylalanine. There was no significant correlation of these results with the clinical score nor with the medical treatment. On the other hand, responses to the calcium ionophore A23187 and to opsonized zymosan showed no significant difference between normal and cystic fibrosis subjects in lysosomal enzyme release. N-formyl-methionyl-leucyl-phenylalanine receptor alterations did not seem involved in the observed effect as demonstrated by Scatchard plot analysis of N-formyl-methionyl-leucyl-phenylalanine binding to these receptors. These results clearly demonstrate a difference between normal and cystic fibrosis neutrophils in release and chemiluminescence responses to N formyl-methionyl-leucyl-phenylalanine stimulation, a difference that might be located in the plasma membrane as both responses are membrane dependent. PMID- 3086829 TI - Postheparin plasma lipoprotein and hepatic lipase activities in hyperinsulinemic infants of diabetic mothers and in large-for-date infants at birth. AB - To study postheparin plasma lipase activities in nonfed newborn infants immediately after birth and to investigate the possible influence of fetal hyperinsulinemia on lipoprotein lipase activity, we measured lipoprotein and hepatic lipase activities in 55 macrosomic newborn infants: group I consisted of 21 infants born to mothers with insulin-dependent diabetes. The infants were hyperinsulinemic at birth and had hypoglycemia and poor lipolysis at the age of 2 h. Group II consisted of 18 infants born to mothers with gestational diabetes. Group III consisted of 16 large-for-date infants born to nondiabetic mothers. The mean postheparin plasma lipoprotein lipase activities at 2 h of age were similar (mean 36 mumol free fatty acids/ml/h; SEM 15) in groups I-III. Lipoprotein lipase activity correlated negatively with cord-serum triglycerides (range 0.13-1.2 mmol/liter) but did not correlate with serum insulin (range 5.4-524 microU/ml) or C-peptide (range 0.6-21.0 micrograms/liter). Hepatic lipase activity was somewhat higher in group I (mean 68 mumol free fatty acids/ml/h; SEM 23) than in groups II and III (mean 55 mumol free fatty acids/ml/h; SEM 14). Hemoglobin Alc was the only important factor explaining the difference in hepatic lipase activities between groups. Lipoproteins and apolipoproteins A-I, A-II, and B were similar in all three groups. We conclude that in large-for-date infants lipoprotein lipase is active at birth without exogenous fat induction, and that these infants are capable of hydrolyzing fat, their main source of energy, immediately after birth. In addition, we conclude that postheparin plasma lipoprotein lipase activity is not affected by fetal hyperinsulinemia. PMID- 3086830 TI - Effect of dose formulation on isoniazid absorption in two young children. AB - In an 8-month-old infant with tuberculous meningitis treatment with isoniazid was unsuccessful and was associated with lower than expected plasma concentrations of isoniazid (measured concentration 0.1 microgram/mL). The infant had received isoniazid as a crushed tablet admixed with apple sauce. Oral administration of the parenteral solution of isoniazid (Nydrazid, Squibb) mixed in apple juice produced a higher isoniazid concentration (2.9 micrograms/mL) and the child improved clinically. Pharmacokinetic studies in two subjects were performed following intramuscular injection of isoniazid and oral administration of (1) an isoniazid tablet crushed and mixed with apple sauce, (2) parenteral isoniazid solution mixed with apple juice, and (3) a commercially available syrup containing isoniazid and pyridoxine (P-I-N Forte, Lannett). Of the three oral preparations, the syrup produced the highest peak concentrations (8.3 and 6.9 micrograms/mL). The crushed tablets in apple sauce produced the lowest peak concentrations (1.4 and 2.4 micrograms/mL). Administration of crushed isoniazid tablets with food may be associated with impaired gastrointestinal absorption, lower than expected isoniazid concentrations, and treatment failure. PMID- 3086831 TI - Pseudomonas aeruginosa otitis externa in an infant associated with a contaminated infant bath sponge. PMID- 3086832 TI - High pressure liquid chromatographic determination of carbocisteine in human plasma and urine. AB - A method is described for the direct analysis of the amino acid carbocisteine in plasma and urine samples, following reaction with dabsyl chloride. Dabsylated carbocisteine is subjected to high pressure liquid chromatography with spectrophotometric detection at 425 nm. The usefulness of the method for bioavailability studies is discussed and compared with methods currently in use. PMID- 3086833 TI - Contribution of coronary endothelial cells to cardiac adenosine production. AB - Experiments were performed in isolated non-working guinea pig hearts perfused according to the Langendorff technique (95% O2, 5% CO2), to evaluate the relative contribution of the coronary endothelium to the formation of cardiac adenosine during hypoxia, hypercapnia, and acetylcholine infusion. For this purpose the adenine-nucleotides of the coronary endothelium were prelabeled by perfusion of isolated hearts with 3H-adenosine (10(-8) M) for 35 min. Changes in the relative specific radioactivity (RSA) of adenosine released into the coronary effluent perfusate were used to assess changes in the relative contribution of the coronary endothelium and cardiomyocytes to total cardiac adenosine release. Hypoxic perfusion (15% O2) doubled coronary flow and increased total adenosine release by about two orders of magnitude and in addition, substantially increased the release of 3H-adenosine. The RSA of adenosine, however, was consistently depressed. During hypercapnic acidosis (9% CO2) the increase in coronary flow was associated with only a small and transient rise in cardiac adenosine release, and did not influence the formation of 3H-adenosine. In the unpaced heart, acetylcholine (10(-7) and 2 X 10(-6) M) dose-dependently increased coronary flow and the release of both adenosine and 3H-adenosine. Within the first minute, the RSA of adenosine was increased, but thereafter was decreased relative to control. In the paced heart, the effects of acetylcholine (2 X 10(-6) M) were greatly attenuated. Increasing coronary flow by bradykinin and isosorbide dinitrate or decreasing heart rate by (-)N6-phenylisopropyl-adenosine did not significantly affect effluent perfusate concentration of adenosine or its RSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086835 TI - [Macrothrombocytosis and idiopathic thrombocytopenic purpura: effect of anticoagulant and prior fixation on the determination of platelet volume using the Coulter system]. AB - This study was designed to evaluate the importance of anticoagulants and of prior fixation on the Coulter Counter platelet size determination in macrothrombocytosis occurring in patients affected with an idiopathic thrombocytopenic purpura (ITP). Native blood was sampled either in an iso-osmotic glutaraldehyde fixative solution at 37 degrees C or in standard citrated or EDTA vacutainers. Platelet size increased from the fixed whole blood sample to the unfixed standard citrate and EDTA samples. There was a good correlation between the three determinations. Of the 23 ITP cases 10 presented large sized platelets both in citrated and in fixed whole blood samples; however 4 of these patients presented a platelet size in the normal range in the EDTA samples. These results show that citrated blood samples are preferable to EDTA samples for detecting an increased platelet size in ITP and that ITP macrothrombocytosis does not result from an abnormal hypervolumetric shape change occurring in vitro after sampling. PMID- 3086834 TI - CO2 responsivity in the mouse measured by rebreathing. AB - We have modified the rebreathing method to study CO2 responsivity in very small mammals. Tidal volume (VT) and frequency (f) of pentobarbital-anesthetized mice were measured during rebreathing from a closed circuit, primed with 95% O2, 5% CO2, through which the gas was constantly circulated at 0.5 l X min-1. The circuit consisted of T-tube from a plethysmograph, Tygon tubing with compliant element, CO2 analyzer and pump, in series. Circuit PCO2 (PctCO2), which was recorded continuously during spontaneous breathing, rapidly equilibrated with end tidal PCO2. CO2 response curves were constructed from extrapolated minute ventilation (V), VT, f and parameters of breath-to-breath timing, respectively, on PctCO2. Analyses of slopes of the response curves, change from onset of rebreathing to peak response, and PctCO2 at which the response peaked revealed that CO2 stimulates V by increasing f and VT and that this is effected by facilitation of central inspiratory-expiratory phase switching and inspiratory drive mechanisms. However, the stimulatory effect of CO2 on phase switching was not sustained, with maximal effect occurring before peak V. The advantages and facility of the modified rebreathing method make it suitable for studies of other small mammals, including neonates. PMID- 3086836 TI - [Familial IgG kappa myeloma in a mother and her daughter. Review of the literature]. AB - The case of a multiple myeloma secreting IgG kappa in both mother and daughter is reported and discussed in the light of previous reports of familial myeloma and myeloma occurring in spouses. In March 1981, the 60-year-old daughter complained of fatigue leading to the discovery of anemia. The diagnosis of myeloma was based on the association of a monoclonal IgG kappa (57.5 g/l) with low serum levels of IgM and IgA and of an increase (38%) in bone marrow plasma cells. She was treated by chemotherapy and by radiotherapy on bone lesions which appeared during the course of treatment. She died in June 1983. In October 1984, the 84-year-old mother was also found to have anemia. The diagnosis of myeloma was based on the association of a monoclonal IgG kappa (24.5 g/l) with low serum levels of IgM and IgA, 0.6 g/l of Bence-Jones protein in urine, an increase (12%) of atypical plasma cells, and of multiple lytic lesions on X-ray. Familial myeloma has been exceptionally reported. We have found only one case in mother and daughter where the myeloma protein was respectively IgA and IgG. The light chain isotype was not determined. Cases of myeloma occurring in spouses have equally been rarely reported in the medical literature. Genetic transmission of chromosomal determinants for myeloma or a type of response to environmental factors have been suspected as well as environmental determinants for myeloma. Genetically abnormal regulation of immunoglobulin synthesis is another possibility. PMID- 3086837 TI - Activation of the Bradyrhizobium japonicum nifH and nifDK operons is dependent on promoter-upstream DNA sequences. AB - Previous analysis of B. japonicum nifH'- and nifD'-'lacZ translational fusions showed that these promoters could be activated by the K. pneumoniae nifA plus the E. coli ntrA gene products. To study the functions of the DNA 5' to these promoters, plasmids carrying deletions in this region were constructed and analyzed in vivo in a heterologous system consisting of an E. coli (NtrA+) background with a plasmid that constitutively expresses the K. pneumoniae nifA gene. Activation of the B. japonicum promoters was completely dependent on sequences located between positions -165 and -100, relative to the start of transcription. Some of the nifD deletion-fusions were mobilized to the wild-type B. japonicum and the exconjugants tested in an ex planta micro-aerobic system, and also used to infect soybean seedlings. The time course of derepression was followed by assaying beta-galactosidase activity from samples withdrawn from the microaerobic cultures or from root-nodule extracts. The results conclusively show that in the homologous system the sequences upstream of the promoter are required to achieve wild-type activity. PMID- 3086838 TI - Tn10 tet operator mutations affecting Tet repressor recognition. AB - The effect of single base pair alterations of the Tn10 encoded tet operator on recognition of Tet repressor was studied in vivo using a repressor titration system and in vitro by dissociation rate determinations of the respective complexes. Both methods reveal that the two operators, O1 and O2, which are in a tandem arrangement in the wild type, are recognized with a two-fold different affinity when separated. Studies on synthetic operator sequences indicate that the Tet repressor binds with higher affinity to the non-palindromic O2 wildtype than to the respective palindromic sequences. The in vivo repressor titration system links the expression of lacZ to the affinity of tet operator to Tet repressor. It was used to isolate tet operator mutations with reduced affinity to the repressor. The in vivo and in vitro obtained results with these mutants agree quantitatively and indicate, that the GC base pairs at positions 2, 6, and 8 are involved in interaction with the Tet repressor. Their importance for recognition decreases in that order. Transitions at position 7 of the tet operator show smaller effects on recognition than transversions. PMID- 3086839 TI - Nucleotide sequence and organization of Bacillus subtilis RNA polymerase major sigma (sigma 43) operon. AB - The gene coding for Bacillus subtilis RNA polymerase major sigma 43, rpoD, was cloned together with its neighboring genes in a 7 kb EcoRI fragment. The complete nucleotide sequence of a 5 kb fragment including the entire rpoD gene revealed the presence of two other genes preceding rpoD in the order P23-dnaE-rpoD. The dnaE codes for DNA primase while the function of P23 remains unknown. The three genes reside in an operon that is similar in organization to the E. coli RNA polymerase major sigma 70 operon, which is composed of genes encoding small ribosome protein S21 (rpsU), DNA primase (dnaG), and RNA polymerase sigma 70 (rpoD). There is a relatively high degree of base and amino acid homology between the DNA primase and sigma genes. The most significant differences between the two operons are observed in the molecular size of the first genes (P23 and rpsU), the complete lack of amino acid homology between P23 and S21, the molecular weights of the two rpoD genes, the size of the intercistronic region between the first two genes, and the regulatory elements of the operon. PMID- 3086841 TI - TFIIIA and homologous genes. The 'finger' proteins. AB - Differential regulation of gene expression, in a precise temporal and spatial pattern during development, is thought to be partly mediated by site specific DNA binding proteins which promote a selective activation of gene transcription. From studies on Xenopus TFIIIA, a factor selectively required for transcription of 5 S ribosomal RNA genes, Miller et al. proposed a novel structural model of interaction between DNA and DNA binding protein. The striking homology of TFIIIA with several recently sequenced Drosophila and yeast gene products suggests that multiple regulatory proteins may have evolved from a small ancestral DNA binding protein domain and that the characteristic features of TFIIIA and TFIIIA-5S DNA interactions may be of general significance. PMID- 3086840 TI - Variable effects of DNA-synthesis inhibitors upon DNA methylation in mammalian cells. AB - Post-synthetic enzymatic hypermethylation of DNA was induced in hamster fibrosarcoma cells by the DNA synthesis inhibitors cytosine arabinoside, hydroxyurea and aphidicolin. This effect required direct inhibition of DNA polymerase alpha or reduction in deoxynucleotide pools and was not specific to a single cell type. At equivalently reduced levels of DNA synthesis, neither cycloheximide, actinomycin D nor serum deprivation affected DNA methylation in this way. The topoisomerase inhibitors nalidixic acid and novobiocin caused significant hypomethylation indicating that increased 5-mCyt content was not a necessary consequence of DNA synthesis inhibition. The induced hypermethylation occurred predominantly in that fraction of the DNA synthesized in the presence of inhibitor; was stable in the absence of drug; was most prominent in low molecular weight DNA representing sites of initiated but incomplete DNA synthesis; and occurred primarily within CpG dinucleotides, although other dinucleotides were overmethylated as well. Drug-induced CpG hypermethylation may be capable of silencing genes, an effect which may be relevant to the aberrantly expressed genes characteristic of neoplastic cells. PMID- 3086842 TI - Undermethylation of interferon-gamma gene in human T cell lines and normal T lymphocytes. AB - The relative levels of DNA methylation at CCGG sequences within and around the interferon-gamma (IFN-gamma) gene in normal human tissues and cell lines were examined by Southern blot analysis using isoschizomeric restriction enzymes, HpaII and MspI. On the test of normal tissues, the IFN-gamma gene was undermethylated only in a small population of T lymphocyte, whereas the gene was fully methylated in T cell-depleted lymphocytes and uterus cells. In TCL-Fuj cell line which is a T cell line producing a high level of IFN-gamma spontaneously, the IFN-gamma gene was undermethylated. Moreover, the extent of DNA methylation was inversely correlated to the level of expression of the IFN-gamma gene in several T cell lines including sublines derived from TCL-Fuj cells. However, partial or complete unmethylation at the CCGG sites of IFN-gamma gene was observed in a promyelocytic leukemia cell line and two epithelial cell lines that fail to produce IFN-gamma irrespective of induction. These results suggest that undermethylation of IFN-gamma gene is necessary but not sufficient for its efficient expression. PMID- 3086843 TI - RNA mapping on Drosophila mitochondrial DNA: precursors and template strands. AB - Drosophila melanogaster mitochondrial DNA (mtDNA) is closely related to the mammalian and amphibian mtDNA except for gene organization. In Drosophila, genes are distributed in clusters alternatively coded on each strand. Besides the eleven major foreseeable transcripts previously described (MERTEN and PARDUE, 1981, J. Mol. Biol., 153, 1-21), we have characterized two poly A+ transcripts, one major and one minor which could correspond respectively to the ND3 and ND6 reading frames, and 27 poly A+ minor transcripts (0.2 to greater than 3.2 kb) which are distributed along the mtDNA except in the rRNAs, ND 1 and A+ T rich regions. The mapping and length of 25 of these transcripts strongly suggest a precursor role. They would be processed at the level of tRNA or tRNA-like sequences. Most of them are transcribed from the template strand of each gene cluster and their distribution is in agreement with the hypothesis of several transcription origins and terminations located near the extremities of each gene cluster. Quantitatively our results show a large variation in each presumptive mature transcript compared to the other, even in a given gene cluster, suggesting a specific degradation of some of the mature transcripts. PMID- 3086844 TI - The human CK gene segment and the kappa deleting element are closely linked. AB - The element which mediates the deletion of the CK gene segment (abbreviations ref. 1) in human lambda light chain producing B-cells was found to be located 24 kb downstream of CK. The kappa deleting element is flanked by hepta- and nonanucleotide recognition sequences similar to the ones adjacent to the JK gene segments. Complementary recognition sequences with a 30 bp spacer were found in the JK-CK intron. For the first time the two partners of a recombination event in a mammalian immunoglobulin gene system have been linked on a physical map. The orientation of the recombination signals of the intron and the Kde sequences allows a joining by a simple deletion mechanism. Similarities and possible differences to the mechanism of V-J joining are discussed. PMID- 3086846 TI - Palindromic sequences are associated with sites of DNA breakage during gene conversion. AB - Gene conversion is a recombinatorial mechanism which transfers genetic information from a donor into a recipient gene. A case of gene conversion between immunoglobulin VH region genes was analysed and palindromic sequences were found to be located near to the left recombinatorial breakpoint, which also is flanked by a direct repeat sequence. We performed a computer search for palindromes and direct repeats in the published sequences of eucaryotic genes which had been involved in gene conversion. In these sequences, the palindrome with the best or second best quality is located near to a breakpoint of recombination. A correlation of recombination breakpoints with direct repeats was not observed. This suggests that gene conversion is promoted by palindromic sequences. PMID- 3086845 TI - Cloning and expression of the rat interleukin-3 gene. AB - Genomic clones carrying the rat interleukin-3 (IL-3) gene have been isolated and the nucleotide sequence of the gene determined. Alignment of this sequence with that of the mouse IL-3 gene has allowed the structure of the rat IL-3 gene to be deduced. The intron-exon boundaries are conserved and extensive nucleotide homology (approx 90%) is present in the 5' flanking region and the portion of the gene coding for the signal peptide. Several proposed regulatory sequences are conserved and an analogous element to the tandem repeat in intron 2 of the mouse gene is also present. The predicted amino acid sequence for mature rat IL-3 shows surprisingly low homology (54%) with its murine counterpart, although all four cysteine residues are conserved. The rat IL-3 gene was expressed in monkey COS-1 cells and colony assays established that rat IL-3 is a multi-lineage haemopoietic growth regulator. There was little cross-reactivity of the respective IL-3 species on mouse and rat bone marrow cells suggesting that rat IL-3, in concert with its receptor, has evolved significantly away from the mouse IL-3/receptor system. PMID- 3086848 TI - Sequence of a leucine tRNA gene from the chloroplast genome of Euglena gracilis. PMID- 3086847 TI - Structure and expression of a human subgroup II immunoglobulin kappa gene. AB - We have determined the entire nucleotide sequence of an active immunoglobulin V kappa gene of the human subgroup II. Comparison of the main coding sequence of this gene to another member of this subgroup reveals germline sequence differences that occur not only in complementarity determining regions but also in framework regions. We find that at least two regions commonly associated with active immunoglobulin genes--the TATAA box and the decanucleotide TGATT-TCAT--are represented in this gene. The gene was expressed by permanent and transient DNA mediated transfection in various cell lines. We have determined the precise site of transcriptional initiation using S1 analysis of gene transcripts and show that this site is the same in the transfected cell lines and in the cell line from which the gene was isolated. PMID- 3086849 TI - Acceptance of transcutaneous nitroglycerin patches by patients with angina pectoris. AB - The acceptance, preference, and side effects of the 3 commercially available nitroglycerin patches were examined in 30 patients with chronic, stable angina pectoris. Patients were serially interviewed after each treatment period regarding patch comfort, aesthetics, discomfort upon removal, adhesiveness, efficacy, and side effects. They were also interviewed and examined for adverse skin reactions. There were significant differences among the 3 patches with respect to comfort, aesthetics, discomfort, and adhesiveness. Skin reactions (mostly mild) occurred in 83% of patients: patch A, 70%; patch B, 43%; and patch C, 57%. Intolerable reactions, which would have caused patch discontinuation, were noted in 40% of patients: patch A, 30%; patch B, 7%; and patch C, 10%. Most patients had an intolerable reaction to only 1 patch. Significant differences were present only between patches A and B with respect to total and intolerable skin reactions. Thus the systems differed in terms of patient preference and skin reactions. Skin reactions are probably more prevalent than previously reported but usually occur with just one of the patches. Physicians and hospitals should probably individualize nitrate patch therapy within formulary and budgetary constraints. PMID- 3086850 TI - Intravenous gamma-globulin in infant acquired immunodeficiency syndrome. PMID- 3086851 TI - [Enteral feeding]. PMID- 3086852 TI - [Evaluation of the therapeutic effect of sodium cromoglycate in patients with gastric and duodenal ulcers, sensitive to exogenous allergens]. PMID- 3086853 TI - The sustained release of LH X RH agonist from LH X RH agonist-polymer composite in patients with prostatic cancer. AB - Luteinizing hormone-releasing hormone (LH X RH) agonist can be administered daily to patients with prostatic cancer with resulting clinical efficacy. A sustained drug release formulation of an LH X RH agonist, (D-Leu6)-des Gly-NH2(10)-LH X RH ethylamide (leuprolide)-vinyl polymer composite, was prepared by means of radiation-induced polymerization under a supercooled state. The sustained release of leuprolide from subcutaneously implanted leuprolide-vinyl polymer composite (14 mm in diameter and 4 mm in thickness) was obtained over a period of several months in five patients with prostatic cancer. Serum testosterone levels began to decrease on the tenth day, fell below 1 ng/ml after three weeks of implantation, and thereafter remained at the castration level until removal of the polymer composite. Clinical improvement was associated with serum hormonal changes, and support this as a novel and superior method of administration of LH X RH agonist. PMID- 3086854 TI - Intramural pseudodiverticulosis--an unusual cause of benign oesophageal stricture. AB - Three cases of intramural pseudodiverticulosis of the oesophagus are described together with a review of the relevant literature. This unusual condition, diagnosed by characteristic features on the barium swallow, is associated with a high incidence of benign oesophageal stricture which responds readily to endoscopic dilatation. PMID- 3086855 TI - Short PR intervals and tachyarrhythmias in Fabry's disease. AB - Two brothers with Fabry's disease presenting with palpitations were found to have intermittent supraventricular tachycardias. Their electrocardiograms, when symptom-free, revealed short PR intervals consistent with ventricular pre excitation. Treatment of one of the brothers with verapamil resulted in improvement of the palpitations and reduction in frequency of the tachycardia. Recurrent supraventricular tachycardia associated with ventricular pre-excitation has not previously been described in Fabry's disease. Evidence suggests that this complication may be due to glycolipid deposition in the conducting system around the atrioventricular node. PMID- 3086856 TI - Asymptomatic Graves' disease during lithium therapy. AB - Lithium salts are widely recognized to cause biochemical hypothyroidism and have been used to treat thyrotoxicosis. We present a case of Graves' disease which developed during lithium therapy. The patient was asymptomatic until the lithium was discontinued; she subsequently developed florid symptoms of thyrotoxicosis. PMID- 3086857 TI - Sodium valproate in epilepsy treatment. PMID- 3086858 TI - Innovation and development in oral and topical antibiotics. PMID- 3086859 TI - [Stress-induced asthma--placebo-controlled double-blind comparison of prevention using fenoterol, disodium cromoglycate and a combination of the two]. PMID- 3086860 TI - [Endocrine function of the testes, gonadotropic and lactotropic activity of the adenohypophysis in impotence among older men]. AB - Endocrine function of the testes, gonadotropic and lactotropic activity of the adenohypophysis have been studied in elderly men with functional sex disorders and during climacterium virile using a radioimmunoassay to determine the levels of testosterone (T), estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin in the peripheral blood plasma. Pathological climacterium virile develops in the presence of sharply raised FSH and prolactin production, an elevated LH level, a decreased T level and a sharp rise of the E2 level. PMID- 3086861 TI - [Bacteriological examination of the urine for detection of urogenital tuberculosis]. PMID- 3086862 TI - [Isolation of Mycobacterium tuberculosis and their L forms from patients with osteoarticular tuberculosis]. PMID- 3086864 TI - [Oxygen and carbon dioxide partial pressure in the alveolar air of patients with nonspecific lung diseases]. PMID- 3086863 TI - [Experience in treating tuberculosis patients in the IB outpatient registry group]. PMID- 3086865 TI - [Identification of mycobacteria using a thin-layer chromatographic method]. PMID- 3086866 TI - Sequence analysis and structure-function correlations of murine q, k, u, s, and f haplotype I-A beta cDNA clones. AB - I-A beta-chain cDNA clones from mice of the q, k, u, s, and f haplotypes have been isolated and sequenced. Nucleotide sequence comparisons among these five A beta chains show considerable allelic variation in the region encoding the first external (beta 1) domain of the mature A beta protein. The beta 1 domain variability is clustered into three discrete regions, two of which divide the A beta chains into subgroups, suggesting an evolutionary history for the separation of alleles in inbred strains of mice. The amino acid sequences of these five chains are compared to each other and to previously published I-A beta chains. Correlations are made between the primary structural differences and the serologic and immune response characteristics mapping to the I-A subregion. PMID- 3086868 TI - Nonrandom segregation of centromeres following mitotic recombination in Drosophila melanogaster. AB - Mitotic recombination is widely used in Drosophila as a technique to study genetic and developmental problems. It has been generally assumed that, following mitotic exchange between homologous chromatids during the G2 stage, the centromeres attached to the chromatids involved in the exchange segregate randomly. As a result, two equally frequent types of segregation, yielding genetically different products, are produced. However, when epidermal or enzymatic cell-marker mutants are used, only one type of segregation gives rise to marked cells. In the present work we test this assumption of random segregation using cytological markers. With cytological markers, larval neuroblast cells resulting from mitotic recombination exhibit recognizably all possible products from mitotic recombination. We find that one type of segregation is favored, in that, after mitotic recombination, the centromeres attached to the chromatids involved in the mitotic exchange preferentially migrate to opposite poles during anaphase. This favored segregation could be the result of exchange between previously oriented chromatids or could be due to the effect of the exchange upon subsequent orientation of homologous chromosomes. In either case, frequencies of mitotic recombination have been overestimated in the past. PMID- 3086867 TI - Molecular cloning and sequence determination of cDNAs for alpha subunits of the guanine nucleotide-binding proteins Gs, Gi, and Go from rat brain. AB - We have cloned cDNAs encoding alpha subunits of the guanine nucleotide-binding proteins Gs, Gi, and Go and determined their nucleotide sequences. Purified preparations of Gi and Go alpha subunits (Gi alpha and Go alpha) from rat brain were completely digested with trypsin, and peptides were subjected to amino acid sequence analysis. By screening of a cDNA library from rat C6 glioma cells with a synthetic probe corresponding to a 17 amino acid sequence, a clone encoding the sequence of Go alpha was obtained. Then, the library was rescreened with a Go alpha cDNA probe to isolate several strongly or weakly hybridizing clones. cDNAs encoding the complete sequences of Gi alpha and Gs alpha were thus obtained. From nucleotide sequence analysis, the amino acid sequences of Gs alpha and Gi alpha were deduced; they contain 394 and 355 amino acid residues (including the initiator methionine), respectively. The calculated molecular weights for Gs alpha and Gi alpha were 45,663 and 40,499, respectively. The Go alpha clone encoded a sequence of 310 amino acid residues that lacked the NH2 terminus. The homology of the alpha subunits of Gs, Gi, Go, transducin, and ras-encoded protein is discussed. PMID- 3086869 TI - Two Drosophila melanogaster mutations block successive steps of de novo purine synthesis. AB - Drosophila melanogaster purine auxotrophs ade2(1) and ade3(1) have been characterized biochemically. The ade2(1) strain is deficient in the fourth step of the de novo purine synthetic pathway catalyzed by phosphoribosylglycinamidine synthase (phosphoribosylformylglycinamide amidotransferase). The ade3(1) strain is deficient in the previous step catalyzed by phosphoribosylglycinamide formyltransferase (GART). The mutation responsible for the slightly leaky ade3(1) phenotype was characterized further. First, the mutant GART polypeptide was found to be of normal size and present at normal levels. Second, the GART-encoding region of the mutant was cloned, inserted into a yeast-Escherichia coli shuttle vector, and used to transform mutant yeast. Transformants showed very slight in vivo activity when compared to wild type, verifying that the mutation is in the GART coding sequence. Lastly, the region of the gene encoding GART activity from mutant and inbred parental strain flies was completely sequenced. A single base transition was found, leading to the substitution of a serine for a highly conserved glycine. These two mutations provide examples of blocks in the de novo purine synthetic pathway in a whole animal. PMID- 3086870 TI - Genes encoding major light-harvesting polypeptides are clustered on the genome of the cyanobacterium Fremyella diplosiphon. AB - The polypeptide composition of the phycobilisome, the major light-harvesting complex of prokaryotic cyanobacteria and certain eukaryotic algae, can be modulated by different light qualities in cyanobacteria exhibiting chromatic adaptation. We have identified genomic fragments encoding a cluster of phycobilisome polypeptides (phycobiliproteins) from the chromatically adapting cyanobacterium Fremyella diplosiphon using previously characterized DNA fragments of phycobiliprotein genes from the eukaryotic alga Cyanophora paradoxa and from F. diplosiphon. Characterization of two lambda-EMBL3 clones containing overlapping genomic fragments indicates that three sets of phycobiliprotein genes -the alpha- and beta-allophycocyanin genes plus two sets of alpha- and beta phycocyanin genes--are clustered within 13 kilobases on the cyanobacterial genome and transcribed off the same strand. The gene order (alpha-allophycocyanin followed by beta-allophycocyanin and beta-phycocyanin followed by alpha phycocyanin) appears to be a conserved arrangement found previously in a eukaryotic alga and another cyanobacterium. We have reported that one set of phycocyanin genes is transcribed as two abundant red light-induced mRNAs (1600 and 3800 bases). We now present data showing that the allophycocyanin genes and a second set of phycocyanin genes are transcribed into major mRNAs of 1400 and 1600 bases, respectively. These transcripts are present in RNA isolated from cultures grown in red and green light, although lower levels of the 1600-base phycocyanin transcript are present in cells grown in green light. Furthermore, a larger transcript of 1750 bases hybridizes to the allophycocyanin genes and may be a precursor to the 1400-base species. PMID- 3086871 TI - Chloramphenicol induces translation of the mRNA for a chloramphenicol-resistance gene in Bacillus subtilis. AB - cat-86 is a plasmid gene specifying chloramphenicol-inducible chloramphenicol acetyltransferase activity in Bacillus subtilis. Inducibility has been suggested to result primarily from activation of the translation of cat-86 mRNA by subinhibitory levels of chloramphenicol. To directly test the involvement of transcription in cat-86 induction, the gene was transcriptionally activated with a strong promoter, resulting in the synthesis of relatively high levels of cat-86 mRNA in uninduced cells. When RNA synthesis was blocked with rifampin (100 micrograms/ml), de novo inducibility of cat-86 by chloramphenicol could be demonstrated for more than 30 min. These results indicate that concurrent transcription is not essential for cat-86 induction. Accordingly, cat-86 is one of only a few inducible bacterial genes in which the primary form of regulation is at the translational level. This form of regulation may apply to other cat genes of Gram-positive origin whose expression is also inducible by chloramphenicol. PMID- 3086872 TI - Class switch recombination is IgG1 specific on active and inactive IgH loci of IgG1-secreting B-cell blasts. AB - Mouse B lymphocytes can be activated polyclonally by bacterial lipopolysaccharide (LPS) to secrete Ig and perform Ig class switch. In the presence of the T-cell lymphokine B-cell differentiation factor, the frequency of IgG1-secreting cells is drastically enhanced. We show here that IgG1-secreting B cells isolated from such cultures have undergone a similar DNA rearrangement of the switch regions (S mu, S gamma 1) of the Ig heavy chain constant region genes C mu and C gamma 1 on both active and inactive IgH loci. This result argues against a stochastic model of class switch recombination and suggests programmed class-specific switch recombination in the case of the switch to IgG1. In accord with this notion, cells expressing IgM but not IgG on the surface have not deleted or rearranged C mu or S gamma 1 on either chromosome. PMID- 3086873 TI - Cotransfer of the Ed alpha and Ad beta genes into L cells results in the surface expression of a functional mixed-isotype Ia molecule. AB - Ia molecules play a key role in antigen recognition by T lymphocytes. To analyze the structural features of the individual alpha and beta chains relevant to the assembly of intact Ia molecules, mouse fibroblasts were cotransfected with various combinations of haplotype- and isotype-mismatched Ia alpha/beta gene pairs. Two important points emerged. First, the level of surface expression of a given haplotype-mismatched A alpha A beta pair appears to depend upon the alpha and beta chain alleles involved. Second, transfection with some isotype mismatched combinations such as Ed alpha Ad beta results in a significant level of surface expression of a stable mixed-isotype dimer, which also appears to be normally expressed at a low level by an Iad-positive B lymphoma. Moreover, a T cell hybridoma specific for human gamma globulin and restricted by the Ed molecule was found to be efficiently stimulated by the Ed alpha Ad beta-positive transfectant in the presence of antigen. The stimulation was specifically inhibited by monoclonal antibodies directed to either the Ia or the L3T4 molecule. These findings suggest that the estimates of the potential number of Ia molecules available in an animal for restricting T-lymphocyte recognition of antigens must be revised. PMID- 3086874 TI - Control of hemopoiesis in mice by sensitized L3T4+ Lyt2-lymphocytes during infection with bacillus Calmette-Guerin. AB - When injected intravenously with bacillus Calmette-Guerin (BCG; 10(7) viable units), C57BL/6 mice rapidly develop a transient anemia associated with an increased number of granulocytes and monocytes, whereas C3H/He mice do not. Because these two features are lacking in C57BL/6 nude mice we postulated that T lymphocytes can regulate hemopoiesis during infection. To assess further the role in hemopoiesis of T lymphocytes present in bone marrow of C57BL/6 and C3H/He mice, the frequency of BCG-specific T lymphocytes and their surface marker phenotype were determined by limiting dilution analysis and use of monoclonal antibodies. The number of BCG-specific T lymphocytes was estimated to be 50- to 100-fold higher in bone marrow of C57BL/6 than in that of C3H/He mice. Although L3T4+ Lyt2-and L3T4- Lyt2+ BCG-specific T lymphocytes were generated in mice of both strains, in C57BL/6 mice L3T4+ cells were induced preferentially from day 1 through day 5 after infection in correlation with hemopoietic changes. The relation between T-cell immune response and hemopoietic changes was substantiated by results obtained after in vivo treatment with monoclonal antibodies. Selective depletion of L3T4+ T cells by in vivo injection of anti-L3T4 monoclonal antibodies (GK 1-5) inhibited the development of the anemia and the related increased production of phagocytes in C57BL/6 mice receiving BCG. PMID- 3086875 TI - Conversion of low-affinity interleukin 2 receptors to a high-affinity state following fusion of cell membranes. AB - The cellular receptors for interleukin 2 (IL-2) exist in at least two forms, one with a particularly high affinity and a second, more numerous class, with a much lower affinity for IL-2. Indirect evidence suggests that both classes of receptors use the same p55 glycoprotein as their ligand-binding component. L cells transfected with cDNA encoding this protein, however, displayed only low affinity IL-2 binding. To determine if such receptors could be converted to a high-affinity state, L-cell membranes containing the murine p55 protein were fused with membranes from human T cells displaying high-affinity receptors. The anti-Tac antibody was used to block ligand binding to human p55 on the fusion product. The results showed that a fraction of the murine p55 chains were converted to a dramatically higher affinity following fusion. Fusion of the L cell membranes with themselves or with membrane preparations from human T-cell lines lacking the IL-2 receptor resulted in little or no affinity modulation. One explanation of the results is that cofactors present in receptor-positive T-cell lines crossed species lines and combined with the murine p55 chain to create "high-affinity" binding sites. Thus, depending upon its environment, the same p55 molecule can apparently form either a low- or high-affinity IL-2 receptor. PMID- 3086876 TI - Cloning of Drosophila choline acetyltransferase cDNA. AB - Choline acetyltransferase (EC 2.3.1.6) is the biosynthetic enzyme for the neurotransmitter acetylcholine. To isolate choline acetyltransferase cDNA clones, a cDNA library was constructed from poly(A)+ RNA of Drosophila melanogaster heads, these being one of the richest known sources of the enzyme. By screening the cDNA library with a mixture of three different monoclonal antibodies to Drosophila choline acetyltransferase, we isolated 14 positive clones. Only 1 of these clones was identified to be a Drosophila choline acetyltransferase cDNA clone based on the following evidence. (i) The amino acid sequence deduced from the nucleotide sequence of the cDNA insert completely corresponded to that of several tryptic peptides from choline acetyltransferase. (ii) The cDNA insert hybridized specifically to only the region on Drosophila polytene chromosomes that had been identified as the site of the choline acetyltransferase (Cha) gene by cytogenetic analysis. The cDNA insert consisted of a coding region 2190 nucleotides long, a 3'-noncoding region 284 nucleotides long, and EcoRI linkers. RNA analysis of Drosophila head poly(A)+ RNA with the cDNA insert as a probe showed the choline acetyltransferase mRNA to be approximately equal to 4700 nucleotides long. PMID- 3086877 TI - Analysis of the phorbol ester pharmacophore on protein kinase C as a guide to the rational design of new classes of analogs. AB - The diterpene diester phorbol 12-myristate 13-acetate and the alkaloid teleocidin B are structurally unrelated natural products that display similar potent irritant and tumor-promoting activities. Computer modeling of these and other structural classes of tumor promoters show a marked similarity in the relative positions of certain heteroatoms and hydrophobic groups. For phorbol this mapping consists of the C-4, C-9, and C-20 hydroxyl groups as well as a hydrophobic region filled by a long-chain acyl functionality attached to either the C-12 or the C-13 positions. Diacylglycerols, thought to be the endogenous activators of the major phorbol ester receptor protein kinase C likewise fit this model in a stereospecific fashion. As an initial test of the utility of the model, members of a new and simplified class of activators were synthesized that possess the predicted essential structural features. These compounds all inhibited specific phorbol ester binding to protein kinase C, albeit with low affinity (10-60 microM); further analysis of one derivative, decylhydroxylindole, confirmed that the inhibition of phorbol ester binding was competitive. This same derivative inhibited epidermal growth factor binding in intact Swiss 3T3 cells and studies with another derivative showed phosphorylation of a 40-kDa protein in platelets. Both of these in vivo responses are characteristic of phorbol esters. PMID- 3086878 TI - Structure of component B (7-mercaptoheptanoylthreonine phosphate) of the methylcoenzyme M methylreductase system of Methanobacterium thermoautotrophicum. AB - Component B, the heat-stable low-molecular-weight cofactor required for methane production by dialyzed cell-free extracts of Methanobacterium thermoautotrophicum, has been purified to homogeneity and its structure assigned. Results of low-resolution fast-atom-bombardment and field-desorption mass spectrometry indicated a molecular weight of 419, and high-resolution fast-atom bombardment mass spectrometry agreed with the molecular formula C13H26NO8PS2. Evidence from fast-atom-bombardment and field-desorption mass spectrometry and 360-MHz 1H NMR in deuterium oxide argued that the compound was isolated as a mixed disulfide with 2-mercaptoethanol; so the proposed elemental formula of the free acid, free thiol would be C11H22NO7PS (molecular weight, 343). The proposed structure for an active form of the coenzyme is 7-mercaptoheptanoylthreonine phosphate. PMID- 3086879 TI - Selective regulation of trypsin gene expression by calcium and by glucose starvation in a rat exocrine pancreas cell line. AB - Treatment of the rat pancreatic acinar cell line AR4-2J with the calcium ionophore A23187 selectively increases, within a few hours, the steady-state level of trypsin mRNA. Addition of the tumor-promoting phorbol ester phorbol 12 myristate 13-acetate potentiates the calcium-induced increase. The mRNA level of the other tested exocrine pancreatic genes decreases. These results were confirmed by DNA transfection experiments, using the 5' flanking region of the trypsin and chymotrypsin genes linked to the coding sequence of the chloramphenicol acetyltransferase (CAT) gene. In calcium-induced cells transfected with the trypsin constructs, an increase in CAT activity was observed, whereas the chymotrypsin constructs revealed a decreased CAT activity. Glucose starvation of AR4-2J cells similarly elicited a selective increase in trypsin mRNA. This selective regulation of trypsin may reflect its role as the key activator of the other zymogen species. PMID- 3086880 TI - Colony stimulating factor-induced differentiation of murine M1 myeloid leukemia cells is permissive in early G1 phase. AB - Granulocyte-colony stimulating factor (G-CSF) induces differentiation of M1 murine myeloid leukemia cells into mature granulocytes/macrophages and also causes accumulation of the cells in the G1 phase of the cell cycle. We examined, therefore, whether synchronization of M1 cells in the G1 phase could affect G-CSF induced differentiation as quantitated by expression of Fc fragment receptors (FcR) and lysozyme activity. Cells were arrested in early G1 by density inhibition in the absence of serum and in late G1 by addition of aphidicolin. Cells synchronized in early G1, when stimulated with G-CSF, showed enhanced expression of FcR and lysozyme activity. Eighty percent of the cells expressed FcR 18 hr after addition of G-CSF while, in exponentially growing cells, this percentage was reached 72 hr after addition of G-CSF. Cells synchronized in late G1 did not show enhanced expression of differentiation markers. These results imply that with respect to G-CSF-induced differentiation, the G1 phase can be separated into an early permissive and a later nonpermissive stage. PMID- 3086881 TI - The arachidonic acid cascade is involved in the masculinizing action of testosterone on embryonic external genitalia in mice. AB - We have evaluated whether the arachidonic acid cascade may be involved in the folding and fusion of the penis and scrotum in masculine differentiation, a possibility raised by recent observations of the involvement of the arachidonic acid cascade in the analogous embryonic processes of elevation and fusion of the palatal shelves and of folding and fusion of the neural tube. To test this hypothesis, during embryonic masculine differentiation in mice of the B10.A strain, we administered certain agents that produce blockade of masculinization. We report that arachidonic acid can reverse the inhibition of masculine development in male embryos produced by estradiol-17 beta or by cyproterone acetate, an androgen receptor-site blocker, and that such reversal can be prevented by an inhibitor of cyclooxygenase, such as indomethacin. We have also found that agents that block the arachidonic acid cascade at the level of phospholipase A2 (cortisone, phenytoin) or at the level of cyclooxygenase (indomethacin, aspirin) also block masculine differentiation and that such antimasculinization is reversed by arachidonic acid. The masculinization of male embryos is inhibited by indomethacin and aspirin, and the masculinization of female embryos produced by exogenous testosterone is prevented by indomethacin. These findings provide evidence that the mechanism by which testosterone organizes the genitalia involves a role of the arachidonic acid cascade leading to prostaglandins at a critical period of development and that interference with testosterone synthesis or action leads to a teratogenic deficiency of arachidonic acid during this time in the genital anlagen. PMID- 3086882 TI - Genetic definition of the translational operator of the threonine-tRNA ligase gene in Escherichia coli. AB - The Escherichia coli gene thrS that codes for threonine-tRNA ligase (tRNAThr ligase, formerly threonine-tRNA synthetase, EC 6.1.1.3) has previously been shown to be negatively autoregulated at the level of translation. Here we describe the use of several thrS-lac gene fusions to isolate cis-acting regulatory mutations that increase the translation but not the transcription of the thrS gene. These mutations lead to a total loss of control of repression and derepression of thrS. DNA sequence analysis locates the mutations between 10 and 40 base pairs upstream of the translation initiation codon of thrS and more than 100 base pairs downstream of the transcription initiation site. The mRNA region where these mutations are located shares primary and secondary structure homologies with specific parts of several isoacceptor tRNAThr species. These findings suggest that the ligase regulates its translation by binding to its mRNA at a place that shares some homology with its natural substrate. PMID- 3086883 TI - The gene encoding the T-cell surface protein T4 is located on human chromosome 12. AB - The surface glycoproteins T4 and T8 define functionally distinct populations of T lymphocytes. We have obtained cDNA and genomic clones encoding the T4 molecule and used these as probes to determine the chromosomal location of this gene. Genomic blotting experiments, along with in situ hybridization analyses, indicate that the T4 gene resides on the short arm of human chromosome 12, at region p12 pter. Thus, the T4 gene is not linked to any known member of the immunoglobulin gene family, including its counterpart gene, T8, which resides on human chromosome 2 immediately distal to the immunoglobulin kappa locus. PMID- 3086884 TI - Phorbol myristate acetate inhibits anti-IgM-mediated signaling in resting B cells. AB - Cross-linking the membrane immunoglobulins of resting B cells leads to activation as judged by increased inositol phospholipid metabolism, intracellular free calcium concentration ([Ca2+]i), and cell volume. Such activated B cells enter S phase in the presence of B-cell stimulatory factor 1. Phorbol myristate acetate (PMA) is a potent inhibitor of anti-IgM- and anti-IgD-stimulated B-cell responses. In B cells concentrations of PMA ranging from 0.1 to 100 ng/ml completely inhibit anti-IgM-stimulated DNA synthesis and block anti-IgM stimulated increases in inositol phospholipid metabolism and in [Ca2+]i. Preincubation periods as short as 4 min block these effects although longer preincubations are somewhat more effective in inhibiting increases in [Ca2+]i. Preincubation with PMA for 1.5 hr does not diminish expression of membrane IgM. This strongly suggests that PMA inhibits responses of resting B cells to anti-IgM by interrupting signal transmission rather than by diminishing cross-linking of membrane immunoglobulin on B cells. In contrast to resting B cells, B cells activated in vitro for 29 hr show enhanced responses to anti-IgM in the presence of PMA. PMID- 3086885 TI - Activation of human peripheral blood mononuclear cells by anti-T3: killing of tumor target cells coated with anti-target-anti-T3 conjugates. AB - Cytotoxic T-cell clones have been shown to be capable of killing unrelated target cells in the presence of heteroconjugates consisting of OKT3 (monoclonal antibody against cell surface antigen T3) and targeting antibody. In contrast, human peripheral blood T cells were not known to have this ability, although these cells have been shown to undergo proliferation in response to OKT3 and accessory signals. Here we report that OKT3-stimulated human peripheral blood mononuclear cells effectively killed human melanoma or Raji cells coated with anti-target cell--OKT3 conjugates. The extent of target-cell killing by stimulated effector cells was much greater than that observed with unstimulated cells, in spite of down-regulation of the T3 structure on the OKT3-treated cells. Target-cell lysis occurred at physiological concentrations of effector cells and was inhibited by monomeric OKT3, indicating that killing was T-cell-mediated. PMID- 3086886 TI - Partial primary structure of the T4 antigens of mouse and sheep: assignment of intrachain disulfide bonds. AB - The T4 antigens of mouse and sheep have been purified to homogeneity and partially sequenced using protein and peptide microsequencing techniques. Both mouse and sheep antigens bear distinct homology to human T4, having an amino terminal segment that is homologous to the K-chain variable region (VK). A surprisingly high degree of sequence divergence was nevertheless evident between the T4 antigens of the three mammalian species, suggesting an unusually rapid rate of evolution that is possibly related to the functional role of T4 in class II major histocompatibility complex antigen recognition. The mouse and sheep T4 antigens contain at least three intrachain disulfide bonds which in all cases connect adjacent cysteine residues. All three intrachain disulfide linkages are situated within the putative extracellular domain, and the amino-terminal disulfide bond probably involves the two cysteine residues homologous to those which form the intrachain bridge within the VK domain of immunoglobulin molecules. The structural relationship of the T4 antigen to other members of the immunoglobulin supergene family is discussed. PMID- 3086887 TI - Role of hydrogen peroxide and hydroxyl radical formation in the killing of Ehrlich tumor cells by anticancer quinones. AB - The cytotoxicity of the clinically important antineoplastic quinones doxorubicin, mitomycin C, and diaziridinylbenzoquinone for the Ehrlich ascites carcinoma was significantly reduced or abolished by the antioxidant enzymes catalase and superoxide dismutase, the hydroxyl radical scavengers dimethyl sulfoxide, diethylurea, and thiourea, and the iron chelators deferoxamine, 2,2-bipyridine, and diethylenetriaminepentaacetic acid. However, tumor cell killing by 5 iminodaunorubicin, a doxorubicin analog with a modified quinone function that prohibits oxidation-reduction cycling, was not ameliorated by any of the free radical scavengers tested. Furthermore, treatment of intact tumor cells with doxorubicin, mitomycin C, and diaziridinylbenzoquinone but not 5 iminodaunorubicin generated the hydroxyl radical, or a related chemical oxidant, in vitro in a process that required hydrogen peroxide, iron, and intact tumor cells. These results suggest that drug-induced hydrogen peroxide and hydroxyl radical production may play a role in the antineoplastic action of redox active anticancer quinones. PMID- 3086889 TI - Slow intravenous administration of low dose aspirin inhibits both vascular and platelet cyclooxygenase activity: an experimental study in the rat. AB - Aspirin irreversibly inhibits cyclooxygenase, thus preventing thromboxane (Tx)A2 production in platelets and prostacyclin in vascular cells. While it is generally accepted that the inhibitory effect of low dose aspirin is cumulative on platelet cyclooxygenase, it is still a matter of debate whether a similar phenomenon also occurs on vascular cyclooxygenase. We have measured in anesthetized rats the inhibitory effect of two doses of aspirin (2.5 and 5.0 mg/kg), given intravenously either as a bolus or as a continuous infusion (for 30 min), on platelet TxB2 and 6-ketoprostaglandin F1 alpha generation by different vascular segments. Aspirin significantly inhibited both platelet and vascular cyclooxygenase independently of the rate of drug administration. The aspirin peak plasma levels at the end of bolus injection was about 170 times higher than the average level measured during the slow infusion (1.21 +/- 0.15 micrograms/ml). At this concentration aspirin did not affect in vitro either platelet or vascular cyclooxygenase activity. Thus the inhibitory effect of aspirin on both platelet and vascular cyclooxygenase seems to be related to total exposure of the enzyme to the drug rather than to the maximal drug concentration attainable in the systemic circulation. These findings may be relevant to the current debate on optimal conditions for the biochemical selectivity of aspirin as an antithrombotic drug. PMID- 3086890 TI - Antimetastatic drugs: function and value. PMID- 3086888 TI - Go, a guanine nucleotide-binding protein: immunohistochemical localization in rat brain resembles distribution of second messenger systems. AB - We have localized a guanine nucleotide-binding protein, Go, in rat brain by immunohistochemistry with a selective polyclonal antiserum to the alpha 39 subunit of Go. Specific staining is widely distributed, abundant in neuropil, absent from neuronal cell bodies, and displays regional heterogeneity. Staining is enriched in cerebral cortex, particularly the molecular layer, neuropil of the hippocampal formation, striatum, substantia nigra pars reticulata, molecular layer of the cerebellum, substantia gelatinosa of the spinal cord, and posterior pituitary. High density staining in the substantia nigra reflects a Go-containing striatonigral pathway since striatal lesions reduce ipsilateral immunostaining in the pars reticulata. Confirming immunostaining, quantitative [32P]ADP ribosylation of nigral membranes with pertussis toxin indicates a 66% +/- 11% (mean +/- SEM) reduction of Go ipsilateral to striatal lesions. Go may be associated with Purkinje cells in the cerebellum since membranes from mutant mice (Nervous), which postnatally lose Purkinje cells, are markedly depleted in pertussis toxin substrate. The localizations of Go correspond in many areas with those of protein kinase C, a component of the phosphatidylinositol cycle, suggesting a major role for Go in the brain related to regulation of the phosphatidylinositol cycle. PMID- 3086891 TI - Tumor autocrine motility factor. PMID- 3086892 TI - Effect of flavonoids on arachidonic acid metabolism. PMID- 3086893 TI - Inhibition of aldose reductase by flavonoids: possible attenuation of diabetic complications. PMID- 3086894 TI - Iodothyronine deiodinase is inhibited by plant flavonoids. PMID- 3086895 TI - Structure-activity relationships of flavonoid deiodinase inhibitors and enzyme active-site models. PMID- 3086896 TI - Inhibition of tumor promotion by flavonoids. PMID- 3086897 TI - Mast cell-dependent immediate hypersensitivity responses. PMID- 3086898 TI - Association of prostaglandin metabolism with urine volume; dissociation from excretion of Na+ and K+ by stress. AB - Stress induced by routine cage cleaning causes retention of Na+ and K+, and increased water and prostaglandin metabolite excretion when measured either against concurrent-controls or against self-control values. This novel stress completely masked the diuretic effects of a long-acting prostaglandin synthetase inhibitor previously observed in a stress-free environment. The results show that prostaglandin synthesis and urine volume regulation are closely associated. They also demonstrate a complete dissociation of urine volume and prostaglandin synthesis regulation from electrolyte regulatory mechanisms in a stressful environment. PMID- 3086899 TI - Comparative clinical trial of isosorbide 5-mononitrate and sustained-release isosorbide dinitrate in ischaemic heart disease. AB - A double-blind crossover study, with placebo periods preceding each active treatment, was carried out in 29 patients with ischaemic heart disease to compare the clinical efficacy of isosorbide 5-mononitrate 40 mg twice daily and the same regimen of sustained-release isosorbide dinitrate. Assessment was by bicycle ergometry, symptomatology and blood nitrate level measurements. After 2-weeks' therapy with isosorbide 5-mononitrate, mean ST segment depression at the highest comparable exercise level for each patient was reduced by 32.5% (p less than 0.01), the mean maximum exercise level was increased from 87 to 102 Watts (17.8%, p less than 0.01), and mean work capacity was increased from 581 Watts-minutes to 783 Watts-minutes (34.6%, p less than 0.01). With sustained-release isosorbide dinitrate, ST segment depression was reduced by 16.5% (p less than 0.05); maximum exercise level showed only a small non-significant increase, from 89 to 97 Watts (8.6%), but work capacity increased (p less than 0.05) from 593 Watts-minutes to 705 Watts-minutes (18.9%). There was no significant difference between drugs as regards ST segment reduction but a slight difference in favour of isosorbide 5 mononitrate (p less than 0.05) in terms of maximal exercise level and work capacity. Both drugs resulted in very small reductions in blood pressure (p less than 0.001 for systolic with isosorbide 5-mononitrate; p less than 0.01 for systolic and p less than 0.05 for diastolic with sustained-release isosorbide dinitrate). Heart rate and rate-pressure product changed little with either drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3086901 TI - Effects of adult or neonatal treatment with 6-hydroxydopamine or 5,7 dihydroxytryptamine on locomotor activity, monoamine levels, and response to caffeine. AB - Rats were treated as neonates or adults with desmethylimipramine (DMI) followed by intraventricular 6-hydroxydopamine (6-HDA) or 5,7 dihydroxytryptamine (5,7 DHT). Locomotor activity of treated rats was measured in photocell cages. Neonatal treatment with 5,7-DHT produced hypoactivity during development while neonatal 6-HDA led to hyperactivity. Treatment of adult rats with 5,7-DHT or 6 HDA, while resulting in equivalent monoamine depletions, was without effect on locomotor activity. The dose response function for caffeine was determined in these rats. Depletion of dopamine by either neonatal or adult treatment with 6 HDA decreased caffeine stimulation of locomotor activity. The adenosine receptor agonist l-phenylisopropyladenosine (L-PIA) decreased locomotor activity in all rats in a dose-dependent fashion. PMID- 3086900 TI - Development of tolerance to the anticonvulsant effect of GABAmimetic drugs in genetically epilepsy-prone gerbils. AB - Three drugs which increase GABA-mediated inhibitory neurotransmission in the brain, namely the GABA degradation inhibitors aminooxyacetic acid (AOAA) and gamma-acetylenic GABA (GAG), and the GABA receptor agonist THIP (gaboxadol), were administered to epilepsy-prone gerbils via subcutaneously implanted osmotic minipumps for 2 weeks. The antiepileptic drugs valproic acid (VPA) and diazepam were also included in the experiments. After one day of constant rate application, all GABAmimetics markedly suppressed seizure activity induced in the gerbils by air blast stimulation, but anticonvulsant efficacy of the drugs was lost after 8 and 14 days of treatment. With VPA, only moderate anticonvulsant effects were found because only sub-therapeutic drug levels (about 40 micrograms/ml plasma) were reached via minipump administration. The experiments with diazepam could only be evaluated in part because of instability of the drug in aqueous solution. Determination of brain GABA metabolism in the gerbils indicated that reduction of GABA synthesis may be responsible, at least in part, for development of tolerance to the anticonvulsant effects of AOAA and GAG. PMID- 3086902 TI - Roles of catecholamine terminals and intrinsic neurons of the ventral tegmentum in self-stimulation investigated in neonatally dopamine-depleted rats. AB - Three series of experiments were undertaken to determine whether the residual catecholamine (CA) terminals or intrinsic neurons of ventral tegmentum (VT) in rats given 6-hydroxydopamine (6-OHDA) after desmethylimipramine (DMI) in the lateral ventricles at birth, mediated VT self-stimulation (SS). In Experiment I, male pups were injected bilaterally on days 3 and 5 with 6-OHDA (total dose 200 micrograms) or with the vehicle after pretreatment with DMI (50 mg/kg, IP) 30 min earlier. Each subject, 150 days old, was implanted bilaterally in the VT with electrode-cannula units. Both the dopamine (DA)-depleted and control groups yielded similar percentages of self-stimulators. The rate of responding was, however, slightly but significantly lower in the DA-depleted group than in the controls. In Experiment II, 8 DA-depleted and 7 control rats were pretreated with pargyline (50 mg/kg, IP) and then given unilateral injections of 6-OHDA in the VT, in the tissue below the SS electrode. These intracerebral injections of 6 OHDA had no effect on VT SS in both groups. Seventeen controls and 12 DA-depleted rats, in Experiment III, were given injections of kainic acid (KA; 5 nM) either ipsilaterally or contralaterally. The ipsilateral injection abolished SS (14 days of testing), whereas the contralateral injection had no effects on ipsilateral SS in both groups. Histochemical fluorescence study in Experiment I and II showed that the neonatal treatment with DMI + 6-OHDA had reduced the number of DA containing perikarya in the VT and that reinjection of 6-OHDA into the VT caused the disappearance of the residual CA terminals in tissue surrounding the electrode tip. PMID- 3086903 TI - Effects of acute and chronic bupropion on locomotor activity and dopaminergic neurons. AB - Acute administration of bupropion (10 or 30 mg/kg) to rats increased locomotor activity in a dose-related manner. The highest dose increased the dopamine (DA) concentration while both doses reduced the concentration of dihydroxyphenylacetic acid (DOPAC) in the striatum. The enhancement of locomotor activity and the decrease of striatal DOPAC concentrations were increased with chronic administration (up to 40 days) of bupropion. The rate of DA synthesis in the striatum was increased by the acute administration of d-amphetamine but was not altered by acute or chronic administration of bupropion. PMID- 3086904 TI - Scopolamine effects on Hamilton search task performance in monkeys. AB - The Hamilton search task, a test of spatial memory, was given to adult monkeys after administration of scopolamine. Three monkeys had been exposed to lead during development and two were controls. The task consisted of opening eight boxes, one per trial, for food reinforcement, with a 20 second delay between trials. The monkey had to remember which boxes it had already opened and avoid them to obtain the remaining reinforcements. Percent correct response, openings to-repeat, trials per session, repetitive index and response latency were measured. There were no significant lead-related effects. Significant scopolamine induced deficits were detected with four of the measures. The low doses of scopolamine (1-3 micrograms/kg) did not affect response accuracy, but 15 and 30 micrograms/kg caused impairments. Only 30 micrograms/kg substantially increased latency. This is like other memory tests in monkeys and rats in that it is sensitive to anticholinergic challenge. Cognitive performance deficits were detected at a dose (15 micrograms/kg) which did not cause increased response latency. The Hamilton search task is a flexible and sensitive memory task for monkeys, analogous to the radial arm maze in the rat. PMID- 3086906 TI - Calcium influence on neuronal sensitivity to ethanol in selectively bred mouse lines. AB - Sensitivity to ethanol, as measured by blood ethanol concentration at loss of righting reflex, was increased significantly in SS but not LS mice following intracerebroventricular (ICV) administration of calcium chloride or A23187, a calcium ionophore. Magnesium chloride or lanthanum chloride, ICV, did not alter sensitivity to ethanol in either SS or LS mice, further indicating a specificity for calcium cation. Calcium was without effect on sensitivity to halothane narcosis in LS or SS mice. Endogenous brain calcium content was similar in these mouse lines, and ethanol administration either in vivo or in vitro did not alter brain calcium concentration. These results indicate that differences in brain sensitivity to ethanol are mediated, in part, by genetic differences in calcium related processes and support the hypothesis that ethanol-induced narcosis may be due to alterations in calcium metabolism in the CNS. PMID- 3086905 TI - Morphine-stimulated feeding: analysis of macronutrient selection and paraventricular nucleus lesions. AB - The hypothalamic paraventricular nucleus (PVN) has been found to be sensitive to the feeding stimulatory effects of opiates. The present experiments investigated the effect of systemic morphine (2 mg/kg) on macronutrient selection in freely feeding and food-restricted rats and assessed the impact of PVN electrolytic and 6-hydroxydopamine lesions on the rats' ability to respond to peripheral morphine injection. In satiated rats, maintained ad lib on pure macronutrient diets, morphine increased food intake. This effect was associated with a preferential increase in protein ingestion; carbohydrate consumption, compared with fat and protein intake, was least affected. In food-restricted rats, permitted to eat for 6 hr, morphine instead produced a particular preference for fat, with no significant enhancement of total calorie intake. While PVN 6-hydroxydopamine lesions, which depleted PVN catecholamine levels by 70%, failed to alter morphine stimulated feeding, electrolytic lesions of the PVN significantly attenuated this response, particularly protein and fat ingestion. This suggests that opiate induced feeding may, in part, be mediated through the PVN, which is known to have an important function in the control of food ingestion. PMID- 3086907 TI - Pharmacokinetics of carbamazepine in protein energy malnutrition. AB - The pharmacokinetics of carbamazepine was studied in 6 children with protein energy malnutrition (PEM) and in 6 healthy children. Plasma carbamazepine was estimated by enzyme multiplied immunoassay technique. Single-dose concentration profiles after 10 mg/kg of the drug showed lower plasma peak levels. The systemic availability (AUC 0-48 h) of the drug in PEM was also reduced. Based on these observations, suggestions have been made for rescheduling the dosage of the drug in PEM. PMID- 3086908 TI - Mobilization of different intracellular calcium pools after activation of muscarinic receptors in pancreatic beta-cells. AB - Exposure to carbachol resulted in a biphasic stimulation of 45Ca efflux when beta cell-rich pancreatic islets from ob/ob mice were perifused with a Ca2+-deficient medium. The pattern of stimulated 45Ca efflux was markedly modified by glucose. Whereas the initial carbachol-stimulated phase was conditional on previous exposure to glucose, the subsequent phase was completely suppressed by 20 mmol/l of the sugar. The stimulatory could be clearly separated also on the basis of a Na+ dependence. Removal of extracellular Na+ resulted in a disappearance of the second phase, but it was still possible to induce a prominent initial peak if depletion of intracellular K+ was prevented when Na+ was omitted. It is concluded that activation of muscarinic receptors in the pancreatic beta-cells results in mobilization of calcium from more than one intracellular pool. Whereas the second phase of stimulated efflux can be explained in terms of an increased entry of Na+ into the beta-cells, the initial stimulation may be due to receptor-mediated breakdown of polyphosphoinositides. PMID- 3086909 TI - The role of lasers in current plastic surgical practice. PMID- 3086910 TI - [Possible uses of Convulsofin liquid in the treatment of pediatric epilepsies]. AB - The effect of Convulsofin-liquidum on several epilepsies and types of seizure in childhood is described. Typical and atypical absences, tonic-clonic seizures of primary generalised epilepsies as well as atonic or myoclonic seizures are considered to be the main indications for the treatment with Convulsofin. To the special advantage of the application in drops especially with infants is referred. PMID- 3086911 TI - Effects of age and diagnosis on thyrotropin response to thyrotropin-releasing hormone in psychiatric patients. AB - The thyrotropin (thyroid-stimulating hormone; TSH) response to thyrotropin releasing hormone (TRH) was studied in 64 age-matched healthy volunteers, 44 patients with endogenous depression, and 21 patients with schizophrenia. A significant negative correlation between delta TSH and age was found both in healthy subjects and in depressed patients. We based our comparison on normal ranges for delta TSH calculated from the delta TSH values in the healthy subjects related to age. It was then seen that blunted TSH response to TRH does not occur significantly more often in depression (13.6%) than in healthy controls (4.7%). Blunted TRH test results were also found in a considerable number of severely ill schizophrenic patients (19%). Application of an improved radioimmunoassay revealed a highly significant correlation between TSH values at baseline and after stimulation, and showed decreased baseline TSH levels in subjects with blunted TRH test results. PMID- 3086912 TI - The TRH stimulation test and the dexamethasone suppression test in depression. AB - The thyrotropin-releasing hormone (TRH) stimulation test and the dexamethasone suppression test (DST) were performed in 40 depressive patients. More endogenously depressed patients than nonendogenously depressed patients showed a blunted response to TRH. No difference was found in delta max thyroid-stimulating hormone (TSH) between patients who responded to dexamethasone administration with a normal suppression of cortisol and those who responded with nonsuppression. PMID- 3086913 TI - Vaccine supply and liability. PMID- 3086914 TI - Health problems of minority groups: public health's unfinished agenda. PMID- 3086915 TI - Gynecomastia among Ethiopian Jews. PMID- 3086916 TI - Access of Hispanics to health care and cuts in services: a state-of-the-art overview. AB - The most current research literature on the access of Hispanics to medical care is reviewed, and data from a 1982 national survey by Louis Harris and Associates on access to health care are presented to document current levels of access to health care of the Hispanic population. Through telephone interviews, 4,800 families were contacted, yielding a total sample of 6,610 persons. According to the survey's data, the ability of Hispanics to obtain health services is hampered by relatively low incomes, lack of health insurance coverage, and ties to a particular physician. However, Hispanics do not differ significantly from whites in their use of hospitals, physicians, or outpatient departments and emergency rooms. Hispanics are less satisfied than whites on a host of measures describing the most recent medical visit. These levels of dissatisfaction with the visit are similar to those of blacks. The recession and public care service cutbacks did not appear to result in a substantial reduction in the volume of medical care received by Hispanics and blacks. Still, the services available to minorities are viewed by them as less effective in meeting their needs in comparison with how whites view the services they receive. Further, the 1982 survey reveals particular difficulties and barriers for Hispanics in obtaining needed medical services. More than one-fifth of the Hispanic families had one or more significant problems in obtaining needed services. PMID- 3086918 TI - Suicide and homicide among Hispanics in the southwest. AB - A study of suicide and homicide among Hispanics of Mexican origin (Mexican Americans) focused on five southwestern States--Arizona, California, Colorado, New Mexico, and Texas--where more than 60 percent of all Hispanics in the United States reside. And 85 percent of them are Mexican Americans. Data were obtained on all suicides and homicides among Hispanics and Anglos (white non-Hispanics), using Anglos as a comparison group. Results for suicide showed the suicide rate for Hispanics (9.0 per 100,000) to be less than the national rate for whites (13.2) and half that of the Anglos residing in the same area (19.2). The lower suicide rate for Hispanics relative to Anglos is seen for both males and females. For homicide, the overall rate for Hispanics (20.5) was more than 2 1/2 times that of Anglos (7.9). The rate for Hispanic men (39.3) was more than three times the rate for Anglo men (11.4). PMID- 3086919 TI - Minnesota plan for nonsmoking and health: multidisciplinary approach to risk factor control. AB - In 1981, the Minnesota Department of Health began a long-term program to control risk factors for the major health problems of the State as determined by an expert committee. The methods chosen to initiate programs were social, economic, and epidemiologic background research and a multidisciplinary statewide planning process. Smoking was considered the most important problem. During 1983-84, department staff members analyzed the epidemiology and economics of smoking in Minnesota and reviewed the literature on methods of smoking control. They and a multidisciplinary technical committee prepared a coordinated plan to increase the prevalence of nonsmoking in Minnesota. The 39 recommendations address mass communication and marketing, educational programs in schools, public and private regulation, economic disincentives through taxation, and funding of programs and evaluation of results. The Minnesota Plan for Nonsmoking and Health was released in September 1984. During the first half year, the plan provided material for formation of a coalition of health organizations to promote nonsmoking. In June 1985, the Minnesota Legislature passed the Omnibus Nonsmoking and Disease Prevention Act, which provides $4 million over 2 years for promotion of nonsmoking through education, regulation, and public communications. These intervention activities will be funded by a portion of a 5-cent increase in cigarette excise tax. The foundations have been laid for what may be the most comprehensive statewide nonsmoking program in the United States. PMID- 3086917 TI - The health of Hispanics in the southwestern United States: an epidemiologic paradox. AB - Recent reports in the literature on the health status of southwestern Hispanics, most of whom are Mexican Americans, are reviewed critically. The review is organized into the following sections: infant mortality, mortality at other ages, cardiovascular diseases, cancer, diabetes, other diseases, interview data on physical health, and mental health. Despite methodological limitations of much of the research, it can be concluded with some certainty that the health status of Hispanics in the Southwest is much more similar to the health status of other whites than that of blacks although socioeconomically, the status of Hispanics is closer to that of blacks. This observation is supported by evidence on such key health indicators as infant mortality, life-expectancy, mortality from cardiovascular diseases, mortality from major types of cancer, and measures of functional health. On other health indicators, such as diabetes and infectious and parasitic diseases, Hispanics appear to be clearly disadvantaged relative to other whites. Factors explaining the relative advantages or disadvantages of Hispanics include cultural practices, family supports, selective migration, diet, and genetic heritage. The recently completed Hispanic Health and Nutrition Examination Survey will go a long way to provide answers to many questions regarding the health of Hispanics in the Southwest or elsewhere. PMID- 3086920 TI - Voluntary reporting system for occupational disease: pilot project, evaluation. AB - For 18 months (1983-84), a pilot program was set up to promote the reporting of occupational disease by physicians to a local health agency. The objectives of the program were to increase the awareness among physicians of occupational disease in their practice, assist physicians in the diagnosis and management of the cases, and to provide a mechanism for public health intervention in hazardous working conditions. After discussions with leaders in the medical community, the program was initiated by a letter from the State Health Commissioner to physicians in the pilot county. A single-page reporting form was included with the letter. A bimonthly newsletter to primary care physicians was also begun. Additional educational activity included presentation of grand rounds and a one day medical conference on the recognition of occupational disease at the single hospital in the county. All physicians reporting occupational disease received copies of all industrial hygiene reports as well as relevant medical literature from the industrial hygienist assigned to investigate all reports by physicians. Only six reports of occupational disease were received. However, three of the six reports resulted in significant intervention. A questionnaire evaluation of the program indicated that there was resistance to involvement in reporting occupational disease, although physicians do recognize occupational disease in their practices regularly. PMID- 3086921 TI - Zuni Diabetes Project. AB - Widespread type II diabetes among North American Indians and certain other populations is a relatively recent medical phenomenon. Increased prevalence of diabetes appears to be related to sudden cultural shifts toward sedentary lifestyle and increased caloric intake. These changes, super-imposed on a genetic predisposition to diabetes, pose a community health threat to the Zuni and similar populations. Regular aerobic exercise is clearly beneficial to most type II diabetics. The key public health issue is how to establish community participation in effective aerobic activity. The Zuni Diabetes Project, fully described here, serves as a model in this respect. PMID- 3086922 TI - Otitis media, hearing loss, and child development: a NICHD conference summary. AB - Growing evidence indicates that a significant relationship exists between the conductive hearing loss resulting from recurrent otitis media (OM) during the first 3-5 years of life and subsequent problems in acquisition of language and academic skills. To assess current knowledge of OM and its consequences for cognitive and linguistic development, to exchange viewpoints, and, if possible, to determine directions for future research, a conference was sponsored by the National Institute of Child Health and Human Development (NICHD). Among the epidemiologic studies cited, some found a very high incidence of OM in North American Indians and Eskimos, caused, according to one hypothesis, by a genetically different eustachian tube. Another researcher advised that basic language development should be carefully assessed in all cases of OM in young children. Conferees agreed that intervention programs must be developed and implemented until preventive measures are available. One model program emphasizes prevention of developmental difficulties based on the known and suspected sequelae of OM and on the known principles of language development. Conference participants recommended that all infants and young children, particularly those at risk, be examined for OM during regular medical checkups. In addition to treating the disorder, measures should be taken to deal with any significant hearing loss. If drug therapy is inadequate to clear effusion from the middle ear, surgery should be considered. Speech and language intervention should be undertaken when required. PMID- 3086923 TI - Community mental health care for the elderly--a look at the obstacles. AB - Despite the recent attention given to mental disorders in the aged and their higher risk for organic mental disorders, older people rarely receive specialized mental health treatment. This paper reviews recent research on some of the major obstacles to the use of treatment by the elderly. These include claims of "ageism" by health care professionals, the negative attitudes and behaviors of older persons toward mental disorders and their treatment, and the failure of general practice physicians to recognize or treat symptoms of mental disorders in their elderly patients or to refer these patients to geriatric mental health specialists. It is suggested that increased public education in geriatric mental health is urgently needed for potential patients, their families, and their general physicians. PMID- 3086924 TI - Curtailment of well child services by a local health department: impact on rural 2-year-olds. AB - The impact of changes in the delivery of well child health services by a rural health department on the reported health status, immunization status, and patterns of health care use is evaluated for poor children born in 1981, when well child clinic services were reduced. Using birth certificate records, all 1981 resident births were enumerated for the case county in Maryland and for a demographically similar comparison county that had continued to operate health department well child clinics. Trained local interviewers tracked and interviewed mothers or guardians of the 1981 cohort. Data were obtained on 567 of 589 eligible children, reflecting a 96 percent response rate. Children in each county were defined as poor if their mothers reported receiving AFDC (Aid to Families with Dependent Children), food stamps, or medical assistance or reported annual household incomes of below +5,000. This poverty status indicator was significantly correlated with health department use in the comparison county. Findings indicate that mothers of poor children in both counties were as likely as mothers of nonpoor children to assess their 2-year-old's health status as good, to identify a regular source of preventive care, and to report complete immunizations for their toddler. Although many private physicians in the case county appear to be seeing poor children in their offices, the distribution of study children among physicians was highly skewed. Out of 19 physicians or health facilities in the case county, one pediatrician was reported as the primary source of pediatric care for 52 percent of the 2-year-olds, one-third of whom were poor. In contrast, no one physician or facility was reported as providing pediatric care for more than 10 percent of 2-year-olds in the comparison county. Findings are discussed in light of these differences in physician supply and practice patterns. PMID- 3086925 TI - Decline in infant mortality of Alaskan Yupik Eskimos from 1960 to 1980. AB - A 1960-62 study of southwestern Alaskan Eskimos documented an infant mortality rate--102.6 deaths per 1,000 live births--that was four times greater than that of U.S. whites. In 1980-81, 20 years after the original study, a similar cohort was identified in this population so that changes in infant mortality and other birth characteristics could be examined. Average birth weight and the amount of prenatal care received by the mothers increased from 1960 to 1980. Birth weight and prenatal visits were positively correlated. Results of the followup also revealed a 1980-81 infant mortality rate--17.1 deaths per 1,000 live births--that was less than a fifth of the 1960-62 rate and no longer significantly different from the national rate. Major changes associated with the decrease in mortality during the first 28 days of life (neonatal mortality) were a significant increase in the proportion of infants born in hospitals and an associated decrease in the number of deaths of infants weighing less than 2,500 grams at birth. The reduction in mortality during the rest of the first year of life was related to a decrease in deaths due to infectious diseases, particularly measles and pertussis. Changes in infant mortality reflect the increased availability of health care in this region, improved immunization programs, and the establishment of the Bethel Prematernal Home in Bethel, AK. PMID- 3086926 TI - Use of physician services following participation in a cardiac screening program. AB - Cardiac screening programs are ineffective when participants with abnormal findings fail to seek treatment and, to a lesser extent, when participants with normal findings use medical facilities unnecessarily because of continuing concern about heart disease. Age, sex, measure of concern about cardiac symptoms and life stress, and abnormal test results were used to predict the use of physician services in the 3 months following screening. Abnormal test results predicted the use of physician services after screening, as did being older, and having life stress and concern about cardiac symptoms. Being older, male, and concerned about cardiac symptoms predicted having at least one abnormal test result. Participants with normal findings and high levels of concern about cardiac symptoms were as likely to see a physician after the screening as were persons with abnormal findings and low levels of concern about cardiac symptoms. Emphasizing participants' concern about symptoms of heart disease or feelings of stress failed to produce an increase in followup for persons who had abnormal screening outcomes. PMID- 3086927 TI - Premarital rubella screening program: from identification to vaccination of susceptible women in the state of Hawaii. AB - Premarital rubella screening programs are effective in identifying women of childbearing age who are susceptible to rubella. There is concern, however, that once identified, susceptible women may not be subsequently vaccinated. Therefore, a study was conducted to test the effectiveness of a motivational letter mailed at the time of serologic testing. Rubella-susceptible women identified by a premarital screening program were randomly divided into two groups: one group of 134 received a motivational letter and one group of 143 did not. Three months later, 52 percent of the women in the motivational group had been vaccinated, compared with only 24 percent (P less than 0.05) of the women in the control group. In this study, a motivational letter was found to lead to a significant increase in rubella vaccination rates among susceptible women. With the increasing emphasis on rubella vaccination programs for adult women, active approaches are necessary to identify and vaccinate susceptible women. PMID- 3086929 TI - [Dosimetry problems with the use of lead filters in radiotherapy with 43 MV bremsstrahlung]. PMID- 3086928 TI - Wolfram (DIDMOAD) syndrome: a complex long-term problem in management. AB - We describe five patients with Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). Three of the patients appear to have had very gradual onset of diabetes mellitus at an early age yet all patients when tested for C-peptide response to glucagon were severely deficient. All patients are registered blind from primary optic atrophy, two have severe hearing difficulties and three high tone sensorineural hearing loss on audiometry. Four patients have cranial diabetes insipidus which in two cases is partial and of gradual onset and was attributed to poor control of the diabetes mellitus. In one case treatment of the insipidus relieved enuresis. All five patients have evidence of dilatation of the urinary tract and one patient is managed in the long-term by self-catheterisation which has resulted in one episode of bacteraemia. One patient has marked testicular atrophy and investigation reveals this to be due to primary hypogonadism and not to hypothalamic-pituitary dysfunction. One female patient had her menarche delayed until the age of 19 years but has subsequently had the only successful pregnancy in a patient with this syndrome of which we are aware. PMID- 3086930 TI - Recombinant human tissue-type plasminogen activator for thrombolysis in peripheral arteries and bypass grafts. AB - Recombinant human tissue-type plasminogen activator (rt-PA) was infused intraarterially at 0.1 mg/kg/h for 1-6 1/2 hours in 25 patients with lower extremity thromboembolic occlusions (13 thrombosed arteries, 12 thrombosed bypass grafts). Occlusion duration ranged from 1 hour to 21 days. Thrombolysis occurred in 23 of 25 patients (92%). Time to lysis varied from 1 to 6.5 hours, with an average time of 3.6 hours. Twenty of 23 patients (87%) in whom thrombolysis was successful benefited clinically from thrombolytic therapy. Twelve of 23 patients (52%) required secondary procedures to maintain arterial segment patency. In 15 of 25 patients (60%) fibrinogen levels were maintained above 50% of baseline values. No major complications directly attributable to rt-PA infusions occurred. rt-PA is a potent, relatively fibrin-specific thrombolytic agent that can achieve rapid thrombolysis while usually avoiding the profound systemic fibrinogenolysis associated with currently available thrombolytic agents. PMID- 3086931 TI - Cryptic structural lesions in refractory partial epilepsy: MR imaging and CT studies. AB - Results of contrast material-enhanced computed tomography (CT) and T2-weighted spin-echo magnetic resonance (MR) imaging were correlated with pathologic findings in 25 patients treated surgically for refractory partial epilepsy. Of 12 lesions present, ten (83%) were detected by MR imaging and seven (58%) by CT scanning. Of nine low-grade gliomas, eight were detected by MR imaging and four by CT scanning. One posttraumatic scar and one case of temporal lobe atrophy were better demonstrated by MR imaging. A small, thrombosed arteriovenous malformation was the only lesion detected by CT scanning but not by MR imaging. No lesions were detected in 13 patients with mild gliosis and one patient with a 1.2-cm grade 1 astrocytoma. Although more sensitive than CT for detection of structural lesions in patients with refractory partial epilepsy, MR imaging resulted in a 25% false-negative diagnostic rate when a repetition time of 2,000 msec and echo time of 60 msec were used. Multi-echo imaging with at least one long echo time may be needed to increase the sensitivity of MR imaging in these patients. PMID- 3086932 TI - Intraoperative US as an aid to intraoperative electron beam radiation therapy. AB - Intraoperative electron-beam radiation therapy (IRT) is being used to treat certain abdominal malignancies. Accurate determination of tumor size, depth, and extent is necessary to select a treatment cone of appropriate size and appropriate electron beam energy for the treatment portal. Fourteen patients undergoing evaluation for this treatment were examined with intraoperative ultrasonography (IUS) to aid therapy planning. IUS study required little additional time and readily delineated tumor size, depth, and relationship to adjacent structures. In two patients, the US and operative findings provided information that precluded use of IRT. The traditional method of tumor evaluation by intraoperative palpation and inspection was consistently enhanced by the use of IUS findings. IUS is a valuable adjunct that improves the accuracy of therapy planning for IRT. PMID- 3086933 TI - Applications of scanning electron microscopy to the study of liver disease. PMID- 3086934 TI - Nonalcoholic fatty liver disease. PMID- 3086935 TI - Non-A, non-B hepatitis: advances and unfulfilled expectations of the first decade. PMID- 3086936 TI - Bio-synthesis of PGD2 and TXB2 by rabbit blood monocytes. AB - A method for the preparation of a highly purified sample of rabbit blood monocytes is described. The metabolism of arachidonic acid (AA) in these cells was studied. Mononuclear cells were prepared by centrifugation on Ficoll-Paque gradients and the monocytes were obtained by further centrifugation and adherence onto plastic culture dishes. These procedures provided a preparation which contained 95% monocytes (non-specific esterase positive). Incubation of [1-14C] AA with these cells produced four major metabolites which were separated by TLC; these corresponded to prostaglandin (PG) D2, thromboxane (TX) B2, 12 hydroxyheptadecatrienoic acid (HHT) and 12-/15-hydroxyeicosatetraenoic acid (HETE). A minor product which co-migrated with PGE2 was also detected but neither 6-keto-PGF1 alpha nor PGF2 alpha were detected. Also, there was no evidence of the formation of 5-lipoxygenase products (5-HETE and LTB4) by rabbit monocytes with or without calcium-ionophore A23187-stimulation. The production of PGD2, TXB2 and PGE2 was further confirmed by analyzing [3H]-AA metabolites using high performance liquid chromatography (HPLC) with tritiated standards as references. The biosynthesis of these compounds from endogenous substrate in A23187 stimulated monocytes was confirmed by specific radioimmunoassays with or without prior HPLC separation. The synthesis of immunoreactive LTB4 and LTC4 by A23187 stimulated cells was also monitored and found to be relatively low. The synthesis of PGD2, TXB2 and PGE2 from both exogenous and endogenous substrate was suppressed by treatment of the monocytes with indomethacin (10(-6) M). PMID- 3086937 TI - Prostacyclin and steroidogenesis in goat ovarian cell types in vitro. AB - Granulosa, theca and corpus luteum cells of the goat ovary were isolated and incubated separately for 6 hours, with or without various modulators. Arachidonic acid (AA, 10 ng to 100 micrograms/ml), the precursor for prostaglandin synthesis, produced a dose-dependent increase in progesterone (P4) and estradiol-17 beta (E2) production by all the cell types. Prostaglandin synthetase inhibitors, aspirin (10(-6)-10(-3)M) and indomethacin (100 ng-1 mg/ml), produced a dose dependent decrease in arachidonic acid-stimulated (100 micrograms/ml) steroid production. Prostacyclin synthetase stimulators, trapidil (1.6 micrograms- 1 mg/ml) and dipyridamole (10(-6)-10(-3)M), when added alone or along with AA, did not affect steroid production. Up to 100 micrograms/ml of U-51605 (9,11-azoprosta 5,13-dienoic acid), a prostacyclin synthetase inhibitor, did not inhibit basal or AA-stimulated steroid production. Prostacyclin (PGI2) and its stable analog 6 beta PGI1 (0.01-10 micrograms/ml) produced a dose-dependent increase in P4 and E2 production in all the three cell types. Increase at 1 and 10 micrograms/ml was significant in all cases. 6-keto-PGE1 (an active metabolite of PGI2 in certain systems) produced an increase in steroid production which was significant in theca at greater than or equal to 1 microgram/ml concentrations but had no significant effect on granulosa and corpus luteum cells at any dose level. 6-keto PGF1 alpha (stable metabolite of PGI2) was without effect in the present system. The lack of effect of PGI2 at lower concentrations was not altered by either differentiation of the cells with FSH and testosterone or addition of steroid precursors, testosterone and pregnenolone. The present results indicate that AA stimulated steroid production in the goat ovarian cell type is mediated by prostaglandins other than PGI2 though PGI2 itself can positively modulate the steroid production. PMID- 3086938 TI - Not prostacyclin synthase but prostaglandin endoperoxide synthase increases with human placental development. AB - Prostaglandin endoperoxide synthase (i.e. cyclooxygenase; PGH synthase) and prostacyclin synthase (PGI synthase) were quantitated with specific immunoradiometric assays in microsomes from human placentae (n = 20) obtained from 7 up to 17 weeks of gestation. Over that period, wherein trophoblastic invasion of the uterine spiral arteries occurs, the placentae showed a significant increase in concentrations of PGH synthase (r = 0.73, p less than 0.001; n = 20), but not in those of PGI synthase. While the variation between individual placentae was much larger for PGI synthase than for PGH synthase concentrations, there was no evidence for a large excess of PGI synthase over that of PGH synthase in any of these early placentae. The data indicate, first, that the developing placenta contains PGI synthase, but in amounts which are relatively small and do not appear to increase with advancing gestation. Second, they seem to indicate that the capacity for bioconversion of arachidonic acid into prostaglandin endoperoxides increases markedly with placental development. PMID- 3086939 TI - Effect of isoquinoline alkaloids on soybean lipoxygenase activity in vitro. AB - Novel isoquinoline alkaloids were evaluated for their effect on the kinetics of a soybean lipoxygenase type I using linoleic acid as substrate. Some of these alkaloids were found to increase the initial reaction velocity, this property seems related to phenolic groups present in the molecule. The effect of these compounds on the soybean lipoxygenase activity was compared to that of others products which are known to affect this reaction. A reaction mechanism is then proposed: it appeared, in this reaction a correlative structure-activity of phenolic compounds we tested. PMID- 3086940 TI - Glutathione peroxidase is neither required nor kinetically competent for conversion of 5-HPETE to 5-HETE in rat PMN lysates. AB - In the 5-lipoxygenase pathway for arachidonic acid metabolism, reduction of 5 hydroperoxyeicosatetraenoic acid (5-HPETE) to 5-hydroxyeicosatetraenoic acid (5 HETE) is catalyzed by an activity different from glutathione peroxidase. Glutathione peroxidase here refers to the nonspecific peroxidase that catalyzes the reduction by glutathione of cumene hydroperoxide and a variety of other peroxides including 5-HPETE. This enzyme is inhibited by mercaptosuccinic acid. Preparations of the 15,000xg supernatant from lysed rat peritoneal polymorphonuclear leukocytes were the source of these activities. Thus, when glutathione peroxidase is inhibited to less than 0.5% of its normal activity by mercaptosuccinic acid, 5-HPETE is reduced as efficiently as in the absence of mercaptosuccinate. In lysate preparations from which endogenous glutathione has been removed, reduction of 5-HPETE is still observed but only in the presence of added reducing agents, e.g., 0.2 mM glutathione. When endogenous glutathione peroxidase is not inhibited, reduction of 5-HPETE occurs at a rate greater than 15-fold faster than can be accounted for by this activity. We conclude, therefore, that the glutathione peroxidase in rat PMNs is not kinetically competent to account for reduction of 5-HPETE. There is a distinct peroxidase that catalyzes this reaction. The 5-HPETE peroxidase can utilize glutathione as reducing agent but is not inhibited by mercaptosuccinate, and additional results indicate that it is inactivated during turnover. PMID- 3086941 TI - Wage justice for aboriginal nurses. PMID- 3086942 TI - The public image of nurses. PMID- 3086943 TI - Diabetes. PMID- 3086944 TI - The QNU and professionalism-activity and achievement. PMID- 3086945 TI - Toxicity of intra-arterial mitomycin C to previously-irradiated tissues. PMID- 3086946 TI - [The role of enemas in the small intestine in the study of ileal subocclusion]. AB - In mechanical subocclusions, when there isn't immediate urgency, is it possible and necessary to probe radiologic examination, for a better surgical evaluation. The authors describe their own experience, achieved in about 3 years, on small bowel double contrast enema. They examined 143 patients; 16 of them were suboccluded. The security and the diagnostic reliability of used method are stressed by the authors to define lesions' morphology and localization. PMID- 3086947 TI - [Axillary brachial plexus block with lidocaine HCl and carbonated lidocaine]. AB - An accordance with the clinical examination recommended by Lanz and Theiss, we studied 26 patients undergoing a blockade of the axillary plexus with lidocaine CO2 or lidocaine-HCl. Furthermore, we determined the blood concentrations of these local anaesthetics. The study showed no significant differences between the two groups of patients, except that the onset of the blockade was more reliable in one group. There was less impairment of motor function than sensory function. Blood lidocaine concentrations amounted to 2.46 mg/l (mean value) within 25 min. Slight cerebral intoxication could be seen in four patients, with no correlation with possibly high lidocaine concentrations. Lidocaine CO2 is recommended as a rapid blockade of short duration in outpatient regional anesthesia. PMID- 3086948 TI - [Comparison of the effect and serum level of mepivacaine HCL and mepivacaine CO2 in axillary brachial plexus anesthesia]. AB - The latency period and spread of axillary plexus block using 40 ml mepivacaine carbonate (1% solution) or mepivacaine hydrochloride was studied in thirty patients scheduled for surgery of the hand-forearm region. The sensory block of the nervus axillaris, musculocutaneus, radialis, medianus, ulnaris and cutaneus brachii medialis was recorded using the pin prick test every 4 min after injection and the motor block was assessed by testing the strength of the corresponding muscles. The only significant difference between the two local anaesthetic solutions was a few more frequent and faster anaesthesia of the nervus musculocutaneus after 16, 20 and 24 min. A comparison between the serum levels of the first five patients of each group showed a faster increase and a higher level after the injection of carbonated mepivacaine. Carbonated mepivacaine doesn't have any practical advantage for axillary plexus block. PMID- 3086949 TI - [Acute rhabdomyolysis in diabetic ketoacidosis and hyperosmolar coma]. PMID- 3086950 TI - [Purification and properties of purine nucleoside phosphorylases from bird liver]. AB - Chicken and pigeon liver PNPases differ in their isoelectric points (5.40 and 5.15), in their molecular weights (125,000 +/- 5,000; 78,000 +/- 5,000, determined on Sephadex G-200) and in their subunit molecular weight (62,000 +/- 10%; 75,000 +/- 10%, determined by sodium dodecil sulfate-polyacrylamide gel electrophoresis). The related molecular weights show a dimeric structure for the chicken liver enzyme and a monomeric structure for the pigeon liver enzyme. Activation energies are similar but differ in delta H values. Both PNPases are irreversibly inactivated by p-chloromercuribenzoate and 5,5'-dithiobis-(2 nitrobenzoic acid) when incubated with these reagents; inactivation can be reverted totally or partially by dithiothreitol and 2-mercaptoethanol. PMID- 3086951 TI - [IgG kappa/IgA lambda biclonal gammopathy. Demonstration of the involvement of 2 different plasma-cell clones using anti-idiotypic antibodies]. PMID- 3086952 TI - [The TRH test in the pathogenetic diagnosis of paroxysmal atrial fibrillation]. PMID- 3086953 TI - Niridazole-induced red/brown urine pigment is associated with increased urinary beta-glucuronidase excretion and a bladder site of formation. AB - Niridazole caused red/brown urine pigment in a man during treatment for Schistosoma mansoni infection. The urine pigment has been observed during niridazole treatment of schistosomiasis, but has not been documented during treatment of other diseases. Urinary beta-glucuronidase (EC 3.2.1.31) concentration increased proportionately to the amount of red/brown pigment in the urine. Concurrently, sterile pyuria developed. The duration of the time urine was in the bladder was directly related to the concentration of beta-glucuronidase and to the intensity of the red/brown urine color, there being much more in infrequently than in frequently voided urine specimens. Pigment development appears to occur in the bladder. The associated and possibly contributing components appear to be niridazole or one of its metabolites, beta-glucuronidase from the kidneys or from urinary granulocytes, and possibly a schistosomal factor. Given time, this combination generated the red/brown pigment. PMID- 3086954 TI - Effect of calcium on in vitro para-aminohippurate accumulation by rat renal cortical slices. AB - In previous studies para-aminohippurate (PAH) accumulation by renal cortical slices was reduced in calcium-free medium when slices are pretreated with calcium (Ca) chelators. Addition of Ca to the incubation medium of these slices reversed the effects of Ca chelation. Based on these studies, it has been proposed that Ca is required for maximum PAH transport by renal cortical epithelium. However, in the studies presented here, we found that PAH accumulation by rat renal cortical slices not exposed to a chelator varied inversely with incubation medium Ca. Differences in accumulation of PAH was not demonstrable until 90 minutes incubation. Also unaffected was the apparent Vmax and Km of initial accumulation and efflux constant. Addition of EDTA to Ca++-free medium reduced PAH accumulation suggesting chelating agents act by a different mechanism than removal of extracellular calcium. PMID- 3086955 TI - Decreased monoamine oxidase activity in stroke-prone spontaneously hypertensive rat kidneys. AB - The present study was undertaken to measure kidney monoamine oxidase activity (MAO) isolated from three different rat groups: Wistar Kyoto rats (WKY), stroke free cases of stroke-prone spontaneously hypertensive rats (SHRSP-control) and SHRSP-stroke cases (SHRSP-stroke). The SHRSP group was found to have less kidney MAO than the WKY group. Conversely, plasma norepinephrine concentration of SHRSP group was significantly higher than that of the WKY group (Jpn. Heart J., 25, 833 835, 1985). These findings suggest that the increased blood pressure in SHRSP may be related to increased plasma norepinephrine concentration caused by a decrease in degradation enzyme, MAO. An attempt was also made to determine the effects of clorgyline and deprenyl. No significant difference in MAO was observed between the kidneys isolated from the WKY, SHRSP-control and SHRSP-stroke groups. However, the inhibition curve of clorgyline reached a plateau after producing 33% inhibition of MAO. It was assumed that rat kidney mitochondrial MAO consists of 33% MAO-A type and 67% MAO-B type. PMID- 3086956 TI - Zinc metabolism in human blood during acute exposure to cold. AB - Effects of acute exposure to cold (10 degrees C for 60 min) on the concentrations of zinc and related proteins in red blood cells and in plasma were studied on seven male students. Lower concentrations of total zinc and of zinc derived from carbonic anhydrase I (CA-I) in red blood cells were found during cold exposure and 15 min after cold exposure, whereas no significant changes occurred in the concentration of zinc derived from carbonic anhydrase II (CA-II) or Cu2Zn2 superoxide dismutase (SOD1). The decrease in total zinc concentration in red blood cells was mostly due to that in CA-I concentration. On the other hand, there were not any changes in total zinc, albumin-bound zinc, and alpha 2 macroglobulin-bound zinc concentrations in plasma during the experimental period. These results, together with the marked hemoconcentration during cold exposure, suggest that cold stress induces an efflux of zinc from plasma. PMID- 3086957 TI - [A new therapeutic approach to infertility in polycystic ovaries: pure FSH]. AB - Current, improved understanding of the physiopathology of polycystic ovary syndrome offers the possibility of more suitable treatment. Formerly, objectives differed for a given patient: re-establish regular cycles using progestogens or estroprogestogens, reduce hirsutism with antiandrogens, trigger ovulation. Clomid is the inducer of choice, but setbacks occur. Injectable gonadotropins were, in principle, a contraindication due to the high incidence of excess stimulation and multiple pregnancy. The introduction of purified FSH offers another method of stimulation. Severe excess stimulation is eliminated with a suitable protocol involving administration of small doses. This offers hope, but as yet no large scale trial has been published. PMID- 3086958 TI - Hospital-medical staff joint ventures: current concepts. PMID- 3086959 TI - [Flunarizine in drug-resistant epilepsies of childhood and adolescence]. AB - Therapeutic effects of flunarizine have been studied on 26 patients, aged from 9 months to 17 years, suffering for epilepsies resistant to common anticonvulsant treatment, despite proper plasmatic levels of drugs. All the cases were monitored with monthly clinical and EEG controls, neuropsychological evaluations and monitoring antiepileptic drugs plasmatic levels. At first, a study was performed on an intra-patient basis: after a basal observation during two months, an open clinical trial was started, using for three months flunarizine 5 mg a day in patients weighing over 10 kg, and 5 mg every two days in children weighing less than 10 kg. Later on, a simple blind clinical trial has been performed on 16 patients, using flunarizine or placebo for three months. The results, obtained in resistant epilepsy of children and adolescent, showed that flunarizine induced in 47.6% of cases a significant reduction of critical (stroke) frequency and intensity, together with normalization of sleeping-waking rhythm, and amelioration of attention performances (vigilance, reactivity, environmental participation). The only side-effect, noticed in 23.8% of cases, was a light diurnal sleepiness, spontaneously regressing after a few days of treatment. PMID- 3086961 TI - A nurse's guide to TPN (continuing education credit). PMID- 3086962 TI - A nurse's guide to TPN. PMID- 3086960 TI - A pilot study in adult rhesus monkeys (M. mulatta) treated with Aroclor 1254 for two years. AB - Aroclor 1254, at a dose level of 280 micrograms/kg body weight equivalent to 200 micrograms/kg/day, was given 5 days per week to rhesus monkeys over a 27 to 28 month period. Terminal clinical signs of varying severity included fingernail detachment, exuberant nail beds, weight loss, stomatitis and normocytic anemia. At necropsy the bone marrow was hypocellular with increased M:E ratio and cytoplasmic vacuoles in erythroid precursor cells. Histopathologic lesions included dilatation of the tarsal gland ducts, atrophy or absence of splenic and lymph node germinal centers, bone marrow depletion, gingival erosion and ulceration, moderate mucinous hypertrophic gastropathy with cystic dilatation of occasional gastric glands, hepatocellular enlargement and necrosis, hypertrophy of biliary duct epithelium, hyperplasia of biliary ducts, hypertrophy of the gall bladder epithelium, and an equivocal increase in the number of lysosomes in thyroid follicular epithelial cells. PCB tissue concentrations were lowest in brain and highest in blood. The results suggest that severe potentially fatal PCB toxicity can develop in rhesus monkeys following ingestion of Aroclor 1254 at 200 micrograms/kg/day for a period of 27 months or longer. PMID- 3086963 TI - When the patient needs TPN at home. PMID- 3086964 TI - The patient on TPN. RN master care plan. PMID- 3086965 TI - Cobalamin absorption determined by the stool spot test. Reliability in patients with uremia or disorders of the ileum. AB - A cobalamin absorption test, the stool spot test (SST), which makes use of radioactive cobalamin and a nonabsorbable isotope, 51Cr-trichloride, has been shown to produce reliable results in patients with pernicious anemia and in healthy controls. The reliability of the SST in patients with bowel disorders and in patients with decreased renal function was investigated by comparing with both whole-body counting and the Schilling test. Fourteen patients with bowel disorders and eight patients with uremia joined the trial. The SST correlated highly significantly with the whole-body counting method. However, the precision of the SST was poor in patients with decreased bowel transit time and inferior to that in the uremic patients. In one of two patients with decreased bowel transit time the two isotopes were shown to have different transit times, thus invalidating the test. In patients with uremia the SST was significantly more reliable than the Schilling test. It is concluded that the SST is reliable also in patients with uremia but may not be reliable in patients with intestinal disorders and decreased bowel transit time. In these patients collection of larger stool samples is recommended. PMID- 3086966 TI - The effect of pentagastrin on the gastric secretion by the totally isolated vascularly perfused rat stomach. AB - Gastric acid and pepsin secretion by the totally isolated vascularly perfused rat stomach was studied. Rat stomachs were vascularly perfused with Krebs-Ringer buffer gassed with 96% O2-4% CO2 and containing 5 mM glucose, 5 mM pyruvate, 4% bovine serum albumin, 10% ovine erythrocytes, and various concentrations of pentagastrin. The gastric lumen was perfused with distilled water gassed with 100% O2. To remove preformed juice and to enable preformed pepsin to be washed out, the initial 20-min gastric juice was discarded. The gastric effluent was then collected continuously for six 10-min periods, and the H+ concentration was determined by titration and the pepsin concentration estimated by a hemoglobin digestion method. Inclusion of pentagastrin in the perfusion buffer increased the acid output dose-dependently from 2.3 +/- 0.4 mueq/h during the control perfusion to a maximum of 12.7 +/- 2.1 mueq/h (p less than 0.01). With the higher doses of pentagastrin and concomitant high acid secretion, gastric acid secretion faded during the collection period. In contrast, gastric pepsin secretion was virtually unaffected by pentagastrin. The present model should be useful for studying the regulation of gastric acid and pepsin secretion. PMID- 3086967 TI - Effects of acetylsalicylic acid on platelet aggregation in male and female whole blood: an in vitro study. AB - We have used the impedance aggregometer to study the in vitro effect of acetylsalicylic acid (ASA) in whole blood (WB) versus platelet-rich plasma (PRP) using blood samples from 24 male and 24 female healthy volunteers. IC50 was calculated from dose-response curves of ADP-, adrenaline-, collagen- and arachidonic acid-induced aggregation. ASA inhibited platelet aggregation in WB with a lower IC50 than PRP in male and female samples; the greater differences between WB and PRP inhibitory effect of ASA were in collagen- and archidonic acid induced aggregation. A higher ASA concentration was needed in order to produce half maximal inhibition of platelet aggregation in female than in male samples with both WB and PRP method, except when ADP was used as the aggregating agent in PRP. PMID- 3086968 TI - Interferon-gamma and pernicious anaemia. PMID- 3086969 TI - Regulation of interleukin 2 receptor expression by interleukin 2. AB - The regulatory influence of Interleukin 2 (IL-2) on the expression of IL-2 receptors (IL-2R) was studied using long-term cultured T-cell lines and recombinant IL-2 (r-IL-2). Three T-cell lines with different growth requirements were used as model systems: insulin-specific BK-BI-1.2 cells express IL-2R transiently after antigenic restimulation, ovalbumin-reactive BK-OVA-1R cells express IL-2R permanently, and BK-BI-2.6.C6 cells bear IL-2R constitutively but do not exhibit antigen reactivity. All three T-cell lines exhibited the property of increased IL-2R expression in the presence of r-IL-2, as tested by cytofluorometry employing monoclonal antibody AMT-13 directed at the murine IL 2R. IL-2R density was influenced selectively by r-IL-2, because the level of Thy 1.2 molecules was similar in the presence and absence of r-IL-2. With BK-BI 2.6.C6 cells, r-IL-2 was shown to upregulate high-affinity receptors. Since BK-BI 2.6.C6 and BK-OVA-1R cells were grown in the absence of feeder cells, these data show that r-IL-2 can regulate the expression of its own receptor without the participation of monokines. Results obtained with the T-cell line BK-BI-1.2, representing insulin-specific T cells with transient IL-2R expression, show that the presence of r-IL-2 did not prevent a decline in IL-2R density occurring on day 5 after antigenic stimulus. This indicates that additional mechanisms besides antigen- and IL-2-induced IL-2R upregulation are operative in controlling IL-2R density on the cell surface. PMID- 3086970 TI - [Nutritional problems related to acute renal insufficiency]. AB - The catabolic stress induced by acute renal failure is multifactorial in origin. Uremia is associated with increased protein degradation presumably due to toxic effects of increased metabolic products and to hormonal alterations. Moreover, anorexia and loss of nutrients during dialysis further contribute to protein energy malnutrition. The goals of nutritional support are to reduce uremia, preserve nutritional status and accelerate renal function recovery. In fact, the indications for enteral or parenteral nutritional support in acute renal failure are primarily founded on clinical criteria rather than on a controlled demonstration of efficacy. The specific metabolic conditions imposed by renal failure on protein, carbohydrate, lipid and micronutrient homeostasis must be addressed. Total parenteral nutrition can be administered safely in acute renal failure, provided strict control of prescription and follow-up is achieved in order to avoid potentially serious complications. PMID- 3086971 TI - Management of acute liver failure. AB - We describe our experience in the treatment of acute liver failure in 620 patients who developed grade 3 or 4 encephalopathy between 1973 and June 1985. The principal aetiologies were paracetamol-induced hepatic necrosis, viral hepatitis, halothane hepatitis and idiosyncratic drug reactions. Cerebral oedema is a major cause of death in these patients and is most effectively treated with mannitol (20%). Renal failure occurs in between 30% and 75% of cases, depending on aetiology, and is most effectively managed by haemodialysis. Electrolyte and acid-base abnormalities are common. Haemodynamic abnormalities encountered include a high cardiac output, low peripheral vascular resistance, hypotension and venodilatation. Assisted mechanical ventilation is frequently required to treat hypoxia caused by pneumonia, atelectasis, haemorrhage and oedema. A coagulopathy is always present but coagulation factors and platelets are given only when the patient is clinically bleeding. These patients are prone to sepsis and this is a significant cause of death. Hypoglycaemia is common and must be actively and frequently sought. The use of charcoal haemoperfusion has been associated with improved survival, especially when it is started during the grade 3 phase of encephalopathy. Recently survival figures of between 47% and 60% have been achieved for patients with paracetamol-induced liver failure and hepatitis A and B. However the figure for non A non B hepatitis and halothane- and drug induced liver failure are disappointing at around 15% and liver transplantation is being explored as a treatment option in these patients. PMID- 3086972 TI - [Parenteral nutrition in liver insufficiency]. AB - In recent years various regimens for parenteral nutrition in liver insufficiency, containing glucose and fat for energy supply and a liver-adapted amino acid mixture for nitrogen supply, have been recommended. The substrates should be delivered in an all-in-one-solution which facilitates metabolic monitoring and decreases the risk of infections. For treatment of hepatic encephalopathy (HE), branched chain amino acids (BCAA) are recommended. The separation of parenteral nutrition from the treatment of HE makes it much easier to adapt the dosage of the BCAA to the clinical symptoms of the patients. In patients with a severe decrease of gluconeogenesis (spontaneous hypoglycemia below 3 mmol/l combined with a hyperlactemia above 7 mmol/l) or a decreased elimination rate of ammonia (production rate of urea nitrogen below 5 g/l combined with hyperammonemia above 100 mumol/l), an exogenous amino acid supply is not indicated. PMID- 3086973 TI - [Acromegaly due to a pancreatic tumor producing growth hormone releasing hormone: clinical picture and morphology]. AB - Acromegaly due to ectopic production of growth hormone releasing hormone (GH-RH) by a tumor is rare, but several cases have been described after isolation and identification of GH-RH from a pancreatic tumor. The authors observed a patient with acromegaly caused by a pancreatic tumor in whom GH-RH production was demonstrated by measurements of GH-RH in peripheral plasma, tumor veins, tumor extracts and immunohistochemical identification. Endocrinological, histological and ultrastructural results are discussed. The problem of potential malignancy is investigated in the light of DNA measurements. This observation shows that GH-RH measurements can be a useful diagnostic procedure before surgery for acromegaly. PMID- 3086975 TI - [Health advice before travel to tropical countries]. AB - Some 8% of Swiss citizens travel in the developing countries annually. Advising these travellers is an important task for the physician, though the most frequent infections are the less serious travellers' diarrhea and common colds. To some extent the more serious tropical diseases can be avoided by appropriate measures, e.g. vaccination (against yellow fever, tetanus, polio etc). and by chemoprophylaxis (malaria). Individual fitness for travel should be checked prior to any journey abroad, and special advice must be given to travellers with special risks (e.g. pregnant women, infants, persons with chronic diseases, diabetics etc.). Most important during a stay in the tropics is a sensible way of life with enough sleep, general hygiene, especially with regard to food, and avoidance of untreated water. Further safety measures are recommended for bathing, strong sun exposure, mountaineering above 10,000 ft and in general for exposure to special health risks. Recognition of risks and their avoidance is often the best prophylaxis. PMID- 3086974 TI - [Travelers' hepatitis]. AB - The growth of international tourism has increased the risk of diseases imported from abroad. Travel in developing countries involves a not inconsiderable risk, particularly of contracting hepatitis A. The risk of B or non A non B hepatitis is less marked, but the prognostic significance is more serious. The incidence, diagnosis and significance of the various types of "traveller's hepatitis", and the possibility of prevention, are discussed. PMID- 3086976 TI - The human immune response to the OKT3 monoclonal antibody is oligoclonal. AB - The availability of highly specific and homogeneous antibodies to human T cells by the hybridoma technique has elicited new interest in the clinical use of antibodies to lymphocytes as immunosuppressive agents. OKT3 is the murine monoclonal antibody that has been the most widely used in clinical transplantation to induce immunosuppression. This antibody recognizes a membrane molecular complex, exclusively present on mature human T lymphocytes, which is tightly linked to the T-cell antigen receptor. The long-term therapeutic use of murine monoclonal antibodies in vivo is hampered by the intense antibody response that occurs in most human patients. Thus, when administered alone, OKT3 manifests its immunosuppressive activity only during the 10 to 15 days that precede the onset of sensitization. The results presented here show, by use of isoelectrofocusing, that the antibody response to OKT3, already reported to be restricted in its specificity (only anti-isotypic and anti-idiotypic antibodies are produced), is in addition oligoclonal. This restriction of the anti monoclonal response may suggest that an efficient way to circumvent the sensitization problem would be to administer consecutively different monoclonal antibodies presenting the same specificity but distinct idiotypes. PMID- 3086977 TI - Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans. AB - Activated mononuclear cells appear to be important effector cells in autoimmune beta cell destruction leading to insulin-dependent (type 1) diabetes mellitus. Conditioned medium from activated mononuclear cells (from human blood) is cytotoxic to isolated rat and human islets of Langerhans. This cytotoxic activity was eliminated from crude cytokine preparations by adsorption with immobilized, purified antibody to interleukin-1 (IL-1). The islet-inhibitory activity and the IL-1 activity (determined by its comitogenic effect on thymocytes) were recovered by acid wash. Purified natural IL-1 and recombinant IL-1 derived from the predominant pI 7 form of human IL-1, consistently inhibited the insulin response. The pI 6 and pI 5 forms of natural IL-1 were ineffective. Natural and recombinant IL-1 exhibited similar dose responses in their islet-inhibitory effect and their thymocyte-stimulatory activity. Concentrations of IL-1 that inhibited islet activity were in the picomolar range. Hence, monocyte-derived pI 7 IL-1 may contribute to islet cell damage and therefore to the development of insulin dependent diabetes mellitus. PMID- 3086978 TI - Mechanisms of memory. AB - Recent studies of animals with complex nervous systems, including humans and other primates, have improved our understanding of how the brain accomplishes learning and memory. Major themes of recent work include the locus of memory storage, the taxonomy of memory, the distinction between declarative and procedural knowledge, and the question of how memory changes with time, that is, the concepts of forgetting and consolidation. An important recent advance is the development of an animal model of human amnesia in the monkey. The animal model, together with newly available neuropathological information from a well-studied human patient, has permitted the identification of brain structures and connections involved in memory functions. PMID- 3086979 TI - Serologic markers of hepatitis B virus infection. PMID- 3086980 TI - Image--reality cleavage in development goals. AB - Within a relatively short time since its inception a lot has been said on the concept of 'Health for All' (HFA). Its meaning and implications have been explored from various angles. Some have praised the idea as the very one we have been waiting for to improve health more effectively. Others have been sceptical. A few, particularly the hard core clinicians and laboratory-oriented health professionals, have been cynical. The overall outcome from the different viewpoints has been almost irreconcilable contradiction. HFA ideas will definitely work, say the proponents; if only we can objectively analyse the meaning and import of HFA, we could select what is feasible and reject the rest, advise the sceptics; HFA, insist the conservative and radical sceptics, is a terminological hotch-potch loaded with so many inexactitudes that the idea lacks direction, feasibility and acceptability even among the ranks of the majority of its proponents. Consequently, planning for HFA has been rather lacklustre in most countries. Failure is often hidden in obscurantist masses of data manipulated to support whatever position is sought to suit the desired situation. Curiously, while there is no dearth of experts on the meaning of data, the reliability of some data leaves much to be desired, their sources and method of collection being as peculiar as the results they imply. But, if the source is unreliable, so must be the outcome. What, then, is HFA and what are the needs to be met? PMID- 3086981 TI - Economics of health and nutrition in Kenya. AB - This paper starts by outlining the present state of health and nutrition in Kenya. Health status for Kenyans has shown spectacular improvement since Kenya's attainment of independence in 1963. Both the infant mortality and crude death rates fell by about 30% between 1963 and 1982. Life expectancy at birth has risen dramatically from 40 years to 54 years over the same period. However, this picture could be misleading because it is possible for the morbidity rate to have risen, or declined only slightly, over the twenty-year period during which mortality rates in Kenya fell substantially. It is further indicated that despite Kenya having per capita availability of nutrients exceeding that recommended by FAO/WHO; about one-third of Kenya's population is unable to meet its food or nutritional requirements. PMID- 3086982 TI - The use of tetracarboxylate fluorescent indicators in the measurement and control of intracellular free calcium ions. PMID- 3086983 TI - Stimulation of hematopoiesis as an alternative to transfusion. AB - Optimal parenteral nutritional support, provided concomitantly with extraordinarily large replacement doses of intravenous iron dextran can be safe, effective, and life-saving for severely anemic patients who cannot or will not accept erythrocyte transfusion. Five patients who had sustained massive acute blood loss and two who had severe chronic anemia received as much as 140 ml of iron dextran intravenously. The average initial hemoglobin value in the patients with acute blood loss was 4.7 gm/dl (range 2.6 to 8.4 gm/dl), increasing to an average of 9.8 gm/dl (range 7.5 to 12.8) in 23.4 days (range 17 to 30 days), a 166% increase. The average initial hemoglobin value in the patients with chronic anemia was 3.7 gm/dl, increasing to 10.5 gm/dl over an average period of 121 days, a 182% increase. Total abdominal colectomy, pyloroplasty with truncal vagotomy, and highly selective vagotomy were accomplished without complications in four of the patients. There were no adverse reactions to the therapeutic regimen, and all patients were discharged in good condition. PMID- 3086985 TI - Muller curved-stem total hip arthroplasty: long-term follow-up of 185 consecutive cases. AB - We reviewed 185 consecutive Muller total hip arthoplasties ten to 14 years after operation. Of the 32 patients with 42 arthroplasties who had died within the ten year period, three had had revisions and five had died of causes related to the operation, including two late infections. Sixty-five hips in 56 living patients were available for clinical and roentgenographic evaluation. An additional 30 hips had been revised for various reasons. When the roentgenographically loose components were combined with the revised ones, the overall incidence of aseptic loosening was 40% for the femoral component and 12.6% for the acetabular component. As previously reported, the combined incidence of loose and revised components at 6 1/2 years was 27.7% for the femoral component and 3.2% for the acetabular component. Therefore, in the intervening five years, the rate of femoral loosening remained about the same, while the rate of acetabular loosening increased. There was a positive correlation between the incidence of loosening of the femoral component and male sex, deficient cementing, and varus position. There was no significant wear of the acetabular component. PMID- 3086984 TI - Cranial nerve deficits due to amyloidosis associated with plasma cell dyscrasia. AB - Cranial nerve dysfunction is exceedingly rare in amyloidosis. Cranial nerve deficits have been described in the very rare form of familial amyloidosis in which there appears to be an autosomal dominant pattern of inheritance. By contrast, they are virtually unreported in the two common forms of amyloidosis, that is, secondary amyloidosis (AA), usually associated with a chronic inflammatory lesion, and primary amyloidosis (AL), resulting from light-chain immunoglobulins of plasma cell dyscrasias. Although neurologic involvement in these forms of amyloidosis has been reported in the peripheral nerves, spinal nerve roots, and autonomic ganglia, the absence of reports of cranial nerve lesions is remarkable. We report the case of a woman with multiple bilateral cranial nerve deficits involving the left trigeminal, left facial, right abducens, and hypoglossal nerves. She had nonfamilial amyloidosis associated with a plasma cell dyscrasia of the IgG kappa type with increased production of light chain immunoglobulins. The rarity of cranial nerve involvement in this clinical setting is highlighted by three previous studies, each of which reported involvement of only a single nerve (either the facial or olfactory nerve). Since aging has been correlated with congophilic changes in the brain, the explanation for the sparing of cranial nerves can be only speculative. PMID- 3086986 TI - [Combined infection with hepatitis viruses B and non-A, non-B]. PMID- 3086987 TI - [Destructive tuberculosis of the respiratory organs in roentgen-positive and roentgen-negative persons]. PMID- 3086988 TI - Breath holding in divers and non-divers--a reappraisal. AB - The two phases of breath holding, the voluntary inactive and involuntary active phases, were identified by non-invasive methods using the induction plethysmograph. Eight trained divers and 7 non-diving control subjects familiar with respiratory apparatus were studied. During breath holding from normocapnia and total lung capacity it was not possible to distinguish between the two groups in respect of the pattern or duration of breath holding or alveolar gas tensions at the breakpoint. Divers could, however, hold their breath much longer after hyperventilation (165 +/- 40.0 and 121 +/- 31.4 seconds; P less than 0.01). This was associated with a longer second phase than occurred in non-divers (78.0 +/- 29.7 and 17.6 +/- 13.1 seconds; P less than 0.01) and more severe alveolar hypoxia (percentage oxygen 7.6 +/- 1.8 and 10.9 +/- 1.7%; P less than 0.01). It is concluded that these divers had a hyperventilation-dependent attenuated hypoxic ventilatory response. Subjects could also be identified who have either a very short (less than 10 seconds) or very long (greater than 45 seconds) second phase. They were considered to be at risk of developing underwater hypoxia and unexpected loss of consciousness. It is further suggested that analysis of the phases of breath holding holds promise as a screening test of both novice and experienced divers. PMID- 3086989 TI - Comparison of Thayer-Martin, Transgrow, and Gonozyme for detection of Neisseria gonorrhoeae in a low-risk population. AB - The Gonozyme test (Abbott Laboratories, North Chicago, IL) an enzyme-linked immunosorbent assay procedure, on-site Thayer-Martin cultures, and Transgrow cultures were compared for sensitivity and specificity in detecting gonorrhea. For these comparisons triplicate genital swab specimens were obtained from women for the diagnosis of infection with Neisseria gonorrhoeae. Both the Transgrow and the Gonozyme specimens were mailed to a public health laboratory. The population under study was considered to be low-risk. When sensitivity and specificity were calculated on the basis of results of Thayer-Martin cultures, Transgrow had a sensitivity of 57% and a specificity of 100%. Gonozyme had a sensitivity of 80% and a specificity of 99%. In a low-risk population, the predictive value of a positive Transgrow culture was 100%, whereas the predictive value of a positive Gonozyme test was 57%. The predictive value of a negative Transgrow result was 99.7%, and that of a negative Gonozyme test was 99.8%. It is concluded that the use of the Gonozyme procedure for screening of low-risk populations needs further evaluation. PMID- 3086990 TI - Approximate molecular weight of envelope protein 1 and colony opacity of Neisseria gonorrhoeae strains isolated from patients with disseminated or localized infection. AB - The patterns of electrophoretic (SDS-PAGE) migration of the major outer membrane protein I of 35 strains of Neisseria gonorrhoeae causing disseminated gonococcal infections (DGI) were compared, and the proportion of colonies expressing the transparent phenotype on a solid medium was determined. Thirty-one of these DGI strains had a protein I of very similar apparent molecular weight (approximately 36,000 daltons), and at least 75% of their colonies on a translucid medium expressed the transparent phenotype. Strains responsible for localized infections and isolated from patients in the same geographic area (Montreal) showed a greater heterogeneity in both apparent molecular weight of protein I and colonial opacity than did strains from patients with DGI. In particular, most prototrophic strains obtained from patients with localized infection had proteins I with molecular weights varying from 35,000 to 38,000 daltons and gave predominantly opaque colonies. PMID- 3086991 TI - Improved diagnosis of gonorrhea in women. AB - Single endocervical cultures are estimated to be 85-95% reliable in the diagnosis of gonorrhea; a properly obtained rectal culture increases this yield by 5%. In this prospective trial, the increased diagnostic yields from two first-day endocervical cultures and second-day endocervical and rectal cultures were examined. The value of cervical gram smears was also reviewed. During a six-month period, 748 women were evaluated on day 1, with 195 returning for second-day cultures. The mean increased diagnostic yields were 2.2% for the second first-day endocervical culture, 2.9% for second-day cultures, and 4.0% for rectal cultures. PMID- 3086992 TI - Cost-effectiveness analysis of transplantation. AB - As organ transplantation has become increasingly effective, difficult questions have been raised about its costs. Cost-effectiveness analysis is one approach that permits relatively straightforward comparisons not only among transplant procedures but among other costly lifesaving therapies. When compared with other such procedures, most organ transplants are found to be cost effective. PMID- 3086993 TI - The influence of preoperative total parenteral nutrition upon morbidity and mortality. AB - This study was done to examine the criteria for determining the adequacy of preoperative total parenteral nutrition (TPN). We hypothesized that an important criterion for adequate preoperative nutrition should be a contraction of the expanded extracellular fluid compartment known to occur in malnourished patients undergoing surgical treatment. Clinical evidence of this included a rise in the serum albumin level and weight loss. Fifty-nine patients requiring preoperative nutritional support for at least five days were admitted to the study. The patients were divided into three groups (group 1, group 2a and group 2b) based upon the response of the patients to TPN. Group 1 consisted of 23 patients who demonstrated a rise in serum albumin value, loss in body weight and diuresis after seven days of TPN. Group 2 was made up of 36 patients who failed to demonstrate a rise in the albumin level in response to nutritional support for one week. Of these patients, 20 underwent operation at the end of a week of nutritional support (group 2a) while 16 patients received four to six weeks of nutritional support preoperatively (group 2b). The complication rate in the three groups was 4.3 per cent for those in group 1; 45 per cent for those in group 2a and 12.5 per cent for those in group 2b (p less than 0.05), group 2a versus group 2b). The results of this study demonstrate a high mortality and morbidity in patients who fail to increase the serum albumin level after one week of TPN. The data suggest that a prolonged period of parenteral nutrition results in a substantial decrease in perioperative complications in this group of patients. PMID- 3086994 TI - The effect of enteral feedings supplemented with pectin on the healing of colonic anastomoses in the rat. AB - The effect of the addition of pectin to an elemental diet on the healing of experimental colonic anastomoses was investigated. Transection and anastomosis of the ascending colon and feeding gastrostomy were performed in 24 Sprague-Dawley rats. All rats then received an elemental diet, and 12 of them had 1% (w/v) citrus pectin added to their diet. On the seventh postoperative day, animals that received pectin-supplemented diets had significantly greater bursting pressures at the anastomoses (266 versus 234 mm Hg, p less than 0.04) and significantly lower colonic mucosal pH (6.2 versus 6.8, p less than 0.001) than animals that received the elemental diet only. The colons from animals fed pectin also had significantly higher hydroxyproline content at the anastomosis than those of the control animals (46.6 versus 40.7 micrograms hydroxyproline nitrogen/mg tissue nitrogen, p less than 0.05). The decreased intracolonic pH is consistent with the hypothesis that improved healing is a local effect mediated by the presence of short-chain fatty acids resulting from the fermentation of pectin. PMID- 3086995 TI - Nonthrombogenic small-caliber human umbilical vein vascular prosthesis. AB - The present investigation demonstrates covalent binding of heparin with carbodiimide to ammonium hydroxide-treated collagenous surfaces. Human umbilical vein grafts (HUVG) outperform carotid arteries of goat, porcine, and canine origin in both heparin loading and stability of the immobilized heparin preparation. The average heparin loading on the untreated carotid arteries and HUVGs and ammonium hydroxide-treated HUVGs were 18, 27, and 31.5 micrograms/cm2, respectively. There was negligible loss of heparin activity under in vitro and in vivo conditions. In vitro studies demonstrate that heparin-bound HUVGs discourage platelet adhesion and subsequent fibrin clot formation. In vivo studies with heparin-bound HUVGs show a significant increase in thrombus-free surface compared with control grafts. Heparin-bound HUVGs also show an enhanced patency rate in the two sets of protocols tested--one lasting for 3 in vivo days (seven grafts) and the other lasting for 7 (15 grafts) in vivo days. The studies conducted so far demonstrate the promise of developing a nonthrombogenic small-caliber HUVG prosthesis. PMID- 3086997 TI - [Clinico-pharmacological study of a new Russian anti-angina preparation dinitrosorbilong]. AB - Eighty patients with ischemic heart disease and stable angina pectoris of effort were examined for the efficacy of dinitrosorbilong (DNL), a new long-acting drug based on isosorbide dinitrate (ID). The anti-ischemic effect of DNL appraised with the aid of repeated exercise lasted about 8h, which was on the average 4 h longer as compared with the duration of the anti-ischemic effect of ID tablets. The regular intake of DNL favoured an appreciable decrease in the number of angina pectoris attacks making it possible to lower nitroglycerin consumption. DNL was well tolerated by the patients. PMID- 3086996 TI - Insulin decreases muscle protein loss after operative trauma in man. AB - Seventy-two hours after major operative trauma, nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acid/m2/day) showed a negative nitrogen balance, increased muscle catabolism, as measured by 3-methylhistidine excretion, increased amino acid efflux from muscle, and decreased circulating levels of insulin. When 5 U of insulin/hr were added to the infusate, arterial insulin levels rose significantly from 39.7 +/- 4.1 microU/ml to approximately the pretrauma levels (74.6 +/- 7.7 microU/ml). Despite this normalization of insulin levels, excretion of nitrogen and 3-methylhistidine and the efflux of amino acids from forearm muscle fell but did not return to pretraumatic levels, suggesting some insulin resistance. Visceral gluconeogenesis from amino acids appeared to decrease, since insulin infusion decreased the efflux of alanine from skeletal muscle with no change in its arterial level. Insulin also significantly reduced the efflux of isoleucine, tyrosine, phenylalanine, glutamine, and total amino acid nitrogen from forearm muscle. These findings, along with the partial reduction in the excretion of 3 methylhistidine and nitrogen, suggest that insulin, in combination with infused calories and protein, decreases the loss of muscle protein after trauma. PMID- 3086998 TI - [Functional status of the hypophyseal-gonadal system in patients with chronic bronchitis]. AB - Sexual function was studied in 76 patients with chronic bronchitis and in 17 healthy males. The study showed a decrease in sexual function of primary hypogonadism type which was in direct relation to the gravity of disease. PMID- 3086999 TI - [Alpha 1-protease inhibitor: characteristics of its biochemical and biological properties and its level in various diseases (review of the literature and personal observations)]. AB - The authors review biological and biochemical properties and the clinical importance of the serum proteases alpha 1-inhibitor with broad-range antiproteolytic activity. Congenital deficiency of this protein is a frequent enough condition linked with predisposition to some diseases of the lungs and liver. Early determination of the deficiency of alpha 1-Pi is fairly urgent, since it permits the early administration of the preventive measures and substitution therapy. The immunochemical technique makes it possible to determine all the varieties of alpha 1-Pi, as they are antigenically similar. Sera from 267 patients with different diseases were examined. The content of alpha 1-Pi was found to be elevated in Waldenstrom's macroglobulinemia, chronic active hepatitis and liver cirrhosis and to be lowered in bronchial asthma. In multiple myeloma and pollinoses, no alterations in the alpha 1-Pi content were recorded. PMID- 3087000 TI - An inhibitor to factor VIII:C in a patient with possible combined haemophilia A and von Willebrand's disease. AB - A factor VIII inhibitor has been found in a patient with an unusual combination of factor VIII-related properties. The inhibitor is directed specifically against the clotting activity (VIII:C) of the factor VIII complex. It behaves in a similar fashion to high responding inhibitors of factor VIII seen in haemophilia A patients and it was characterised as an immunoglobulin of the IgG class. Laboratory results from the patient and his family show considerable variation of factor VIII-related properties between various individuals. Overall, the data suggests the co-existence of haemophilia A and von Willebrand's disease in the family and the presence of both diseases in the patient. PMID- 3087001 TI - Determination of soluble fibrin in plasma by a rapid and quantitative spectrophotometric assay. AB - A rapid, sensitive and quantitative spectrophotometric assay of soluble fibrin in plasma samples has been developed. The method is based on the principle that fibrin stimulates the activation of plasminogen by tissue plasminogen activator (t-PA). A sample containing fibrin is incubated with t-PA, plasminogen and a plasmin-sensitive chromogenic substrate. An increase in absorbance which is dependent on the fibrin concentration in the sample is obtained. In plasma samples an initial lag-phase, due to the presence of alpha 2-antiplasmin is observed. However, the change in A405 per square minute during the later part of the reaction was found to be proportional to the fibrin content and to generate linear standard curve intercepts at the origin. The detection limit of bathroxobin-digested fibrinogen added to plasma was about 5 nmol/L. Recovery experiments at 20 and 75 nmol/L levels in plasma samples from healthy individuals were excellent. The "within-run" variation (CV) was determined as 3.7%. The formation of fibrin after addition of minute amounts of thrombin to plasma could be monitored with the method. Plasma from 8 healthy individuals was found to contain about 9.2 +/- 1.9 nmol/L fibrin. Plasma samples from 46 patients with a suspected haemostatic disturbance had higher levels of soluble fibrin (53 +/- 62 nmol/L). Seven of the 46 samples had concentrations above 150 nmol/L. PMID- 3087002 TI - Platelet function in experimentally induced pancreatitis in the dog. AB - Evidence suggests that changes in prostaglandins and disseminated intravascular coagulation accompany pancreatitis. Both may induce changes in platelet function. We wished to determine if experimentally induced pancreatitis in the dog was associated with altered platelet number and function, and whether there were concomitant changes in prostaglandins. Evidence for disseminated intravascular coagulation in the dogs with pancreatitis were red blood cell fragmentation, increased platelet turnover indicated by macro-platelets and the transient presence of fibrin degradation products in urine. There were no significant changes in platelet count. The platelets from dogs with pancreatitis showed a functional defect characterized by significantly decreased aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. Release of adenosine triphosphate from platelets was reduced in collagen-stimulated aggregation. There were no changes in the plasma concentrations of thromboxane B2, 6-Keto-PGF1a, and PGE2. This defect may have been due to the generation of fibrin degradation products and platelet "exhaustion". PMID- 3087003 TI - Visualization of von Willebrand factor multimers by immunoenzymatic stain using avidin-biotin peroxidase complex. AB - A technique for the detection of von Willebrand factor multimers separated by discontinuous SDS agarose electrophoresis has been developed using non radioactive compounds. The multimeric patterns were visualized by monospecific anti-human vWF:Ag followed by incubation with biotinylated antibody. After addition of avidin-biotin-peroxidase complex, the peroxidase activity was detected by 4-chloro-1-naphthol, giving sharp bands with a clear background. By this method, the differences of vWF:Ag multimers could be easily observed between normal plasma and the plasmas from variant type vWD (IIA, IIB, platelet-type). Large and intermediate multimers were absent in the plasma with vWD type IIA, while only large multimers were absent in the plasma with vWD IIB and platelet type. The absence of large multimers was also observed in two commercial FVIII preparations having the ratio of vWF/vWF:Ag 0.18 and 0.63. The preparation with the ratio of 0.63 showed the presence of larger intermediate multimers. Electrophoresis in SDS 1.5% agarose gel revealed triplet structure of each small multimer, and a relative increase of the smallest subband was observed in vWD IIA plasma, platelet-type vWD plasma and commercial FVIII preparations. The procedures described are easy and safe to perform and are useful for screening or classifying cases with vWD in general laboratories. PMID- 3087004 TI - Identification of t-PA as the major active plasminogen activator in human milk. AB - Human colostrum and milk contain high levels of plasminogen activator when compared with blood. These levels are inversely related to the duration of lactation and the activity appears to be due to tissue type plasminogen activator present in multiple (65-190 Kd) molecular weight forms. PMID- 3087005 TI - Effect of a thymic factor on the concentration of a factor VIII inhibitor in a patient with treated Hodgkin's disease. PMID- 3087006 TI - Anesthetics and anticoagulants used in the preparation of rat platelet-rich plasma alter rat platelet aggregation. AB - Aggregation of platelets in heparin- and citrate-anticoagulated platelet-rich plasma (PRP) from rats anesthetized with methoxyflurane (M), diethyl ether (E), acepromazine/ketamine (A/K), or sodium pentobarbital (P) is described, as are platelet counts. Platelet counts were highest in heparin- or citrate-PRP from E and A/K anesthetized rats. Collagen and arachidonic acid (AA) induced aggregation in heparin-PRP only, and ADP induced greater aggregation in heparin-PRP than in citrate-PRP. Differences between citrate-PRP and heparin-PRP are probably due to citrate inhibition of platelet aggregation, since addition of citrate to heparin PRP decreased aggregation, while addition of heparin to citrate-PRP did not alter aggregation. Aggregation of hirudin-PRP was slightly less than heparin-PRP. Anesthetics affected rat platelet aggregation: the rank order of the maximal extent of ADP-induced aggregation in citrate-PRP was M greater than E = A/K greater than P, and that for AA and collagen in heparin-PRP was E = A/K greater than M = P. The correlation between the effect of the anesthetics and activation of the sympathoadrenal system is discussed. It appeared that of the commonly used anticoagulants and anesthetics, heparin and methoxyflurane had the least influence on rat platelet aggregation. PMID- 3087007 TI - The combined effects of 2,3-DPG and Na-arachidonate on platelet aggregation and on TXA2 formation. AB - We have investigated the effects of 2,3-DPG on platelet aggregation in the presence of suboptimal concentrations of Na-Arachidonate by using the two cuvette transfer experiments of Hamberg, Svensson and Samuelsson (3). The results show that 2,3-DPG enhanced or induced platelet aggregation in the presence of suboptimal concentrations of Na-Arachidonate. Imidazole, a TXA2 synthetase inhibitor, and Lasix, when added inhibited 2,3-DPG effects on platelet aggregation, suggesting that 2,3-DPG may act either on cyclooxygenase or on TXA2 synthetase of prostaglandin synthesis. A specific RIA assay showed that 2,3-DPG when added to suboptimal concentrations of Na-Arachidonate enhanced the formation of TXB2, a stable metabolite of TXA2. We have concluded that during intravascular hemolysis 2,3-DPG release may be a key component in preventing and/or inducing thrombosis. PMID- 3087008 TI - Thrombolytic effect of single-chain pro-urokinase in a rabbit jugular vein thrombosis model. AB - The thrombolytic effect of single-chain pro-urokinase (SCPU) was examined in the rabbit using a jugular vein thrombosis model. Infusion of a low dose (120,000 IU/kg) of either urokinase (UK) or SCPU did not produce any significant thrombolysis. However, UK administration at such a low dose caused 20% degradation of circulating fibrinogen. A high dose (480,000 IU/kg) caused significant thrombolysis. The degree of fibrinogenolysis was about 20% in SCPU, but about 80% in UK. The thrombolytic efficiency of SCPU was thus about 3 times larger than that of UK. Analysis of fibrinolytic parameters such as plasminogen, alpha 2-plasmin inhibitor, etc. suggested that UK caused systemic activation of the fibrinolytic system, but SCPU, locally limited activation on the fibrin surface (fibrinolysis). These results indicate that SCPU represents a highly efficient thrombolytic agent without producing fibrinogenolysis. PMID- 3087009 TI - Inhibition of rabbit platelet activation by lipoxygenase products of arachidonic and linoleic acid. AB - The hydroperoxy fatty acids, 15-hydroperoxyeicosatetraenoic acid (15-HPETE), 13 hydroperoxy and 9-hydroperoxyoctadecadienoic acid (13- and 9-HPODE) and the corresponding hydroxy compounds (15-HETE and 13-HODE) were synthesized and purified. Washed rabbit platelets were incubated with these fatty acid derivatives before aggregation was induced. Arachidonic acid-induced aggregation, as well as the secretion of ATP and the formation of thromboxane B2 (TXB2) were dose-dependently inhibited by these compounds. Low thrombin-, collagen- and ADP induced aggregations were also suppressed by 15-HPETE. Platelet activation induced by the calcium ionophore A23187 and by high thrombin concentrations were not affected by 15-HPETE. In addition, doses of 15-HPETE which were inactive by themselves, potentiated the anti-aggregating activity of prostacyclin (PGI2). It is suggested that the hydroperoxy and hydroxy compounds suppress platelet activation by interference with the rise in cytoplasmic calcium in addition to the inhibition of cyclo-oxygenase. PMID- 3087010 TI - Protective activity of defibrotide against lethal acute myocardial ischemia in the cat. AB - Defibrotide (D) is a natural polydeoxyribonucleotide from mammalian lungs with profibrinolytic and antithrombotic activities. D also has PGI2-stimulating and tissue plasminogen activator (TPA)-releasing activities, but has no anticoagulant properties. The protective effects of D were demonstrated very recently in a model for non-lethal ischemia in the cat. In the experiments reported here Defibrotide was tested in a model for acute myocardial ischemia leading to ventricular fibrillation (VF) and death of the cat. Occlusion of the coronary artery (LAD) at its origin induced VF and death in 17 of 20 control cats. When cats were treated with D (32 mg Kg-1, bolus i.v., + 32 mg Kg-1 h-1, i.v., after LAD occlusion) 19 of 20 animals survived until the end of experiments. D also prevented changes in plasma and myocardial CPK, hemodynamics and ECG. D was compared with a variety of pharmacological agents which are used clinically for specific cardiovascular diseases. The ability of D to promote considerable generation of PGI2 from vascular walls plus its ability to prevent the decreases in CPK-activity and ATP in the myocardial tissue may have roles in its beneficial effects against ischemic heart in the cat. However, the mechanism/s of the substantial protective effect of D against cardiac death has still to be clarified. PMID- 3087011 TI - Estrogen regulation of tissue plasminogen activator in a human melanoma cell line. AB - The influence of ethinylestradiol and the three natural estrogens, i.e. estrone, 17-beta-estradiol and estriol, was studied in a melanoma cell line producing a tissue-type plasminogen activator (t-PA). The cell cultures were exposed to the four estrogens by addition of the steroids dissolved in a weak alcoholic solution to the culture media, in which the released t-PA was assayed by an immunoradiometric method. Ethanol (0.76% w/v) stimulated the t-PA production, while no significant effect of the estrogens in the concentration of 1.7 X 10(-7) M was seen. By tenfold increase in estrogen concentration a highly significant reduction of t-PA levels was recorded in the cultures exposed to ethinylestradiol and 17-beta-estradiol. Estriol differed from these two estrogens in having rather weak inhibitory effect; whereas estrone in this concentration had toxic effect on melanoma cells. It was concluded that the present estrogens, in particular ethinylestradiol and 17-beta-estradiol, had a dose-dependent inhibitory effect on the production of t-PA in melanoma cell culture. PMID- 3087012 TI - Factor VIII coagulant activity and von Willebrand factor in post-exercise plasma from standardbred horses. PMID- 3087013 TI - Pharmacokinetics of a new heat-treated concentrate of factor VIII estimated by model-independent methods. AB - We evaluated the pharmacokinetic properties of Kryobulin TIM3, a new heat-treated Factor VIII concentrate which has recently become available in Europe. Twelve patients with classic hemophilia were studied. In each patient, Factor VIII was given as a single dose (ranging from 11.6 to 30.3 units/kg) after which eight serial blood samples were drawn to characterize the disappearance of Factor VIII from the plasma. Model-independent (noncompartmental) methods were used for pharmacokinetic analysis. The following pharmacokinetic parameters of Factor VIII (mean +/- SD) were estimated: clearance = 3.83 +/- 0.99 ml/h/kg; mean residence time = 15.9 +/- 4.5 h; volume of distribution at steady state = 55.6 +/- 9.3 ml/kg; in-vivo recovery = 129 +/- 29%. The pharmacokinetic parameters of Kryobulin TIM3 obtained in our study are very similar to those previously reported for the untreated concentrate. Thus, our findings suggest that the dosing guidelines previously available for the untreated concentrate need not be revised when using the treated product. PMID- 3087014 TI - Inhibition of tissue thromboplastin-mediated blood coagulation. AB - Factors affecting the inhibition of tissue thromboplastin (TP)-mediated blood coagulation have been investigated. Human brain thromboplastin progressively loses procoagulant activity when incubated in the presence of defibrinated plasma and CaCl2. Inhibition is maximal at a CaCl2 concentration of 1.5 mM during incubation and involves the calcium dependent binding of a plasma component(s) to the TP-FVII complex, preventing the activation of FX. Chelation of calcium ions using EDTA releases active TP and FVII from the inhibited complex. No inhibition occurs during incubation of TP with Al (OH)3 adsorbed plasma and calcium ions unless a Factor VII concentrate (or purified FVII and FX) is also present. Incubation of TP with antithrombin III-deficient plasma and calcium ions also leads to inhibition. Moreover, purified AT III cannot substitute for adsorbed plasma in producing TP inhibition. The data are consistent with the presence in plasma of a potent AT III independent inhibitor of TP-mediated blood coagulation. PMID- 3087015 TI - Plasminogen activator inhibitors in plasma and platelets from patients with recurrent venous thrombosis and pregnant women. AB - Using affinity chromatography on lysine Sepharose 4B, a fast-acting tissue plasminogen activator inhibitor (t-PAI) was partially purified from t-PAI-rich plasma from patients with recurrent DVT. Its inhibition of tissue plasminogen activator (t-PA) was demonstrated in functional assays and its reaction with 125I t-PA was analyzed by autoradiography following SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis). When the t-PAI was mixed with an equimolar concentration of t-PA at 37 degrees C, the half-life of free one-chain and two chain 125I-t-PA was 1.8 and 0.8 min, respectively. The rate of complex formation between 125I-t-PA and t-PAI was similar both in patient plasma, pregnancy plasma and platelet lysates made from platelet-rich normal, patient and pregnancy plasma. The molecular weights of the complexes between t-PA and the inhibitors in patient plasma and in the different platelet lysates were identical, while that of the inhibitor complex formed in pregnancy plasma was found slightly higher by SDS-PAGE indicating that the pregnancy plasma t-PAI differs from the fast-acting t-PAI found in plasma from thrombotic patients and in platelet lysates. PMID- 3087016 TI - Requirement of free carboxyl groups for the anticoagulant activity of heparin. AB - The uronic acid carboxyl groups of a heparin fraction with high anticoagulant activity, were converted to the methyl ester by treatment with diazomethane. The product obtained after purification did not have the characteristic activity of heparin in accelerating the inhibition of thrombin or factor Xa, by antithrombin. Esterification also abolished the binding of heparin to antithrombin as measured by changes in the intrinsic fluorescence. It is concluded that free carboxyl groups are essential for the activity of heparin. PMID- 3087017 TI - The effect of noise and starvation on the tissue plasminogen activator activity. PMID- 3087018 TI - [Parenteral nutrition of newborn infants. Work Group Parenteral Nutrition of the Section Perinatology]. PMID- 3087019 TI - Association of HLA class I antigens (A1, B5, B8 and CW2) with disease manifestations and infection in human schistosomiasis mansoni in Egypt. AB - The present study was designed to examine the possible association of HLA antigens and schistosomal hepatosplenomegaly and colonic polyposis in a large number of patients and controls. The results show that hepatosplenomegaly was significantly associated with the presence of two HLA antigens: HLA-A1 and B5; and colonic polyposis to HLA-B5 and B8. Furthermore, asymptomatic infection was significantly seen more in subjects with CW2. These results point to possible gentic factors controlling the pathogenesis of disease and susceptibility to infection in human schistosomiasis. PMID- 3087020 TI - HLA, blood groups and secretor status in patients with established rheumatic fever and rheumatic heart disease. AB - The distribution of HLA-A, -B and -DR antigens as well as blood groups and secretor status was studied in sporadic, North Indian patients of rheumatic fever and rheumatic heart disease. While HLA-Aw33 occurred with an increased frequency in the patient group (X2 = 4.01), no statistically significant differences were observed in the frequency of B-locus antigens. In the DR locus, HLA-DR3 was found to be significantly increased (50% vs 26.1%, X2 = 13.8) and DR2 significantly reduced (21.8% vs 47.0%, X2 = 15.6). Also, there was a preponderance of non-'O' blood group individuals in the patient group as compared to controls. The DR3 association was significant only in those patients of RHD who did not have any previous history of rheumatic fever. These results indicate that susceptibility to rheumatic heart disease is HLA-class II mediated, with HLA-DR3 influencing susceptibility and DR2 conferring protection. PMID- 3087021 TI - Impaired clearance, elimination, and metabolism of plasma cholesterol esters associated with hypercholesteremia in mice fed cyclopropenoid fatty acids. AB - Swiss-Webster mice were fed corn oil control diet or 0.7% cyclopropenoid fatty acid (CPFA) for 8 weeks and dosed iv with an equimolar suspension of [3H]cholesteryl palmitate and [14C]cholesteryl palmitoleate. Blood decline of labeled sterol was biphasic. There were no differences in vivo plasma cholesterol ester metabolism, elimination kinetics, or fecal elimination rate for labeled sterol from [3H]cholesteryl palmitate or [14C]cholesteryl palmitoleate within CPFA or control groups. However, compared to controls, CPFA animals diverted significantly more labeled sterol into saturated and diunsaturated cholesterol esters, less into mono- and tetraunsaturated esters, and showed decreased blood clearance and fecal elimination of labeled sterol. Biliary elimination was probably not impaired by depressed hepatic cholesterol esterase activity in CPFA fed mice. The fundamental effect of CPFA on serum cholesterol concentration appears to reside in a severely imbalanced cholesterol ester profile. Results indicate that CPFA alter normal fatty acid profile of serum cholesterol esters by proportionally altering the C-2 fatty acyl composition of serum phospholipid, which is the substrate for lecithin:cholesterol acyltransferase, the major source of plasma cholesterol esters. PMID- 3087022 TI - Effects of 2,4-dithiobiuret treatment in rats on cholinergic function and metabolism of the extensor digitorum longus muscle. AB - Effects of 2,4-dithiobiuret (DTB) treatment in rats on neuromuscular transmission and the disposition of cholinergic substances, acetylcholine (ACh) and choline (Ch), were examined in a combined electrophysiological/biochemical study using an in vitro extensor digitorum longus (EDL) muscle-peroneal nerve preparation. EDL muscle preparations isolated from rats treated with DTB (1 mg/kg/day X 5 days, ip) displayed a 49% depression in the frequency of miniature end-plate potentials (MEPPs) and a 21% depression in mean MEPP amplitude. Statistical analysis of evoked end-plate potentials (EPPs) measured in curarized preparations indicated that the mean quantal content (m) was significantly depressed in EDL muscles from DTB-treated rats. At stimulation rates of 1, 10, 20, and 50 Hz the estimated values of m in EDL preparations from DTB-treated rats were, respectively, 21, 25, 45, and 51% of that in control preparations. Biochemical determinations of ACh and Ch revealed a significant DTB-induced increase in endogenous ACh and Ch content in EDL preparations fixed for extraction of ACh and Ch immediately after dissection from the treated rats. In vitro, however, there were negligible changes in overall ACh synthesis since the total (tissue and medium) tracer ACh (2H4-ACh) synthesized from tracer Ch (2H4-Ch; 10 microM) supplied in the perfusion medium was similar in EDL preparations from DTB-treated and control rats. Also, in EDL muscles from DTB-treated rats the resting release of ACh was not affected, but when exogenous Ch (2H4-Ch) was not supplemented in the medium the evoked release (via peroneal nerve stimulation) of ACh was depressed. Thus, decreases in spontaneous quantal ACh release, as detected in the electrophysiological experiments, were not reflected by changes in the biochemically determined ACh resting release. The biochemical determination of evoked ACh release, however, correlated with the decrease in quantal content detected in the electrophysiological analysis of evoked EPPs when exogenous Ch was not supplemented in the perfusion medium. Significant and consistent increases (two to three times) in both Ch content and efflux occurred in the EDL muscles from DTB-intoxicated rats. These results indicate that DTB induces a prejunctional impairment of neuromuscular transmission that is not specifically directed at ACh synthesis. Rather those processes by which ACh is incorporated into or released from vesicles appear to be altered. PMID- 3087024 TI - Modification of biliary tree permeability in rats treated with a manganese bilirubin combination. AB - Previous studies in this laboratory demonstrated incorporation of manganese (Mn) and bilirubin (BR) in rat liver bile canalicular membrane (BCM) following a cholestatic regimen composed sequentially of Mn plus BR. The present study investigates biliary tree permeability using segmented retrograde intrabiliary injection (SRII) with [3H]mannitol and [3H]inulin as marker substances. Male Sprague-Dawley rats were given the following iv: (a) Mn (high and low dose), (b) BR, (c) sulfobromophthalein (BSP), (d) Mn-BSP-BR, (e) MnBR. Results obtained with mannitol showed a approximately 63% decrease (p less than 0.05) in marker recovery following administration of MnBR combination. While BSP alone had no effect on mannitol recovery, BSP abolished the MnBR response when administered in the Mn-BSP-BR sequence. With inulin, Mn (high dose), MnBR, and Mn-BSP-BR all produced a approximately 45% decrease (p less than 0.05) in recovery, while BSP or BR alone caused a approximately 25% decrease (p less than 0.05). Mn (low dose) was without effect. These results and others obtained when the time pattern of the MnBR treatment was modified suggest: (1) MnBR treatment increases biliary tree permeability by altering both BCM and the junctional complex; (2) BCM alteration is probably the more critical event, since BSP, which protects against MnBR cholestasis, protected against the MnBR-induced change in mannitol recovery, but exerted no effect on inulin recovery. PMID- 3087023 TI - Temporal effects on antipyrine metabolite kinetics in Aroclor 1254-treated rats. AB - The in vivo consequences of a single dose of Aroclor 1254 (50 mg/kg) on the drug metabolizing capacity of rats were investigated. A noninvasive method, employing [N-methyl-14C]-antipyrine where both 14CO2 exhalation and urinary excretion of 4 hydroxy-, 3-hydroxymethyl-, and norantipyrine were monitored, was used. A group of rats were sequentially tested over a 3-week period to characterize temporal patterns. The antipyrine metabolite kinetic approach demonstrated that induction of hepatic cytochrome P-450 is maximal 3-6 days after Aroclor 1254 administration and the effects were apparent for at least a further 14-17 days. Evidence is presented to suggest selective effects of Aroclor 1254 on different cytochromes P 450 are apparent in vivo. PMID- 3087025 TI - Protection by uridine diphosphoglucuronic acid and DT-diaphorase against the cytotoxicity of polycyclic aromatic hydrocarbons isolated from a complex coal gasification condensate. AB - The cytotoxicities of polycyclic aromatic hydrocarbon (PAH) subclasses isolated from a complex organic mixture (coal gasification condensate) were studied in vitro in Chinese hamster ovary cells, in the presence of rat liver microsomes from animals pretreated with Aroclor. Toxicity was enhanced by microsomal metabolism and was inversely related to aromatic ring number. Rat liver cytosol, semipurified DT-diaphorase, and uridine diphosphoglucuronic acid decreased the cytotoxicity of a variety of PAH mixtures and representative PAH, as well as individual PAH metabolites. The results indicate that the in vitro toxicity of complex PAH mixtures is caused primarily by hydroxy-PAH and quinone metabolites of the predominant, nonmutagenic two- and three-ring PAHs. PMID- 3087026 TI - Failure of carbon disulfide and levothyroxine to modify the cardiovascular response of rabbits to a high-cholesterol diet. AB - Exposure of rabbits for 12 weeks to 300 ppm carbon disulfide (CS2) for 6 h/day, 5 days/week, or to 25 mg/day of thiourea or 2% cholesterol in the diet, or to any combination thereof caused a significant reduction in the concentration of serum thyroxine (T4). The reduction of the concentration of serum T4 in rabbits by the treatments was completely offset by the inclusion of 0.1 mg/day of sodium levothyroxine in the diet. Ingestion of feed containing 2% cholesterol significantly increased the degree of atherosclerosis present in the aortic arch and significantly increased the oil red O positive lipid present in the heart and the aorta, with the aortic arch being the most severely affected. The response of the aorta and the heart to the 2% cholesterol diet was not significantly modified by concurrent exposure to CS2 by inhalation or by treatment with thiourea, a metabolite of CS2. We found no evidence that the development of cardiovascular lesions induced by a 2% cholesterol diet in rabbits was mediated by a mechanism involving a component of hypothyroidism. PMID- 3087027 TI - The role of enzyme activity and charge properties on the presynaptic neurotoxicity and the contracture-inducing activity of snake venom phospholipases A2. AB - Two toxic phospholipases A2, caudoxin from Bitis caudalis venom and the basic phospholipase A2 from Naja nigricollis venom, were selected for a study of the contribution of enzyme activity and charge properties to the presynaptic neurotoxicity and the contracture-inducing activity of the enzyme. Reducing catalytic activity by lowering the incubation temperature or by substitution of Sr2+ for Ca2+ in the bathing medium causes a significant prolongation of the time to neuromuscular block by caudoxin, but does not change the contracture-inducing activity of Naja nigricollis basic phospholipase A2. In the chick muscle pretreated with heparin, the latter enzyme fails to evoke contracture, whereas the presynaptic neuromuscular blocking action of caudoxin remains little affected. Histidine-modified Naja nigricollis enzyme, which has lost 95% of its enzyme activity, retains considerable ability to induce contracture and to abolish indirectly evoked contraction, while lysine-methylated enzyme, which loses only 10% of its enzyme activity, almost completely loses its ability to evoke muscle contracture. It is concluded that enzyme activity is important for the presynaptic effects of caudoxin, but not for the contracture-inducing action of the Naja nigricollis enzyme. In the latter enzyme certain easily methylated lysine residues are critical for its ability to induce muscle contracture. PMID- 3087028 TI - Thaumetopoein: an urticating protein from the hairs and integument of the pine processionary caterpillar (Thaumetopoea pityocampa Schiff., Lepidoptera, Thaumetopoeidae). AB - Hairs of the Thaumetopoea pityocampa caterpillar (Lepidoptera) cause a cutaneous reaction in man and animals. The irritating fraction extracted from hairs contains soluble proteins which were separated by various electrophoretic and immunoelectrophoretic techniques. Some of these proteins are present also in cuticle and haemolymph. One protein of 28,000 mol. wt is hair specific and caused a reaction in pig skin identical to that produced by hair extract. It is therefore an urticating protein which we have named thaumetopoein. This protein is formed of two subunits of molecular weights 13,000 and 15,000. It is present in large quantities in the glands producing urticating hairs. PMID- 3087029 TI - Comparison of two methods for proteolytic enzyme detection in snake venom. AB - An acrylamide gel system containing fibrinogen was used to detect proteolytic enzymes in snake venoms. Proteolytic activity was observed as a clear area on a blue background after electrophoresis and overnight incubation in Tris buffer, prior to staining with Coomassie blue. Venoms from eastern and western diamondback and west coast Mexican rattlesnakes, Crotalus adamanteus, C. atrox and C. basiliscus basiliscus, respectively, and southern copperhead, Agkistrodon contortrix contortrix, were analyzed at the level of 1 mg of venom. The effect of the serine proteinase inhibitor diisopropylfluorophosphate (DFP) and the metalloproteinase inhibitors tetraethylenepentamine (TEP) or EDTA on fibrinogen and normal gel profiles were evaluated. Normal gels (without fibrinogen) were Coomassie stained to visualize migration of 250 micrograms of venom proteins on the gels. Several proteolytic enzymes detected in C. atrox and C. b. basiliscus venoms were inhibited by TEP, whereas DFP had no effect on activity. The fibrinogen gels detected no protease activity in C. adamanteus venom, although it is known from other studies that there are several proteolytic enzymes in this venom. Several proteases were detected in A. c. contortrix venom, one of which was inhibited by TEP. By comparison, proteolytic activity in 5-10 micrograms of all venoms was readily detected using the mammalian plasma kallikrein specific chromogenic substrate, S2302 (H-D-Pro-Phe-Arg-p-nitroanilide). The fibrinogen gel method does not appear to have the specificity nor the sensitivity of the recently developed chromogenic substrates for detection of proteolytic enzymes in snake venom. PMID- 3087030 TI - The pharmacology of anatoxin-a(s), a neurotoxin produced by the freshwater cyanobacterium Anabaena flos-aquae NRC 525-17. AB - Anatoxin-a(s) [antx-a(s)] is produced by Anabaena flos-aquae clone NRC 525-17 and is different from anatoxin-a, a known depolarizing agent produced by A. flos aquae NRC 44-1. Purification of antx-a(s) from lyophilized cells involved extraction with 1.0 M acetic acid: ethanol (80:20), column chromatography (Sephadex G-15 and CM-Sephadex C-25) and high performance liquid chromatography. Purified toxin has an LD50 (i.p., mouse) of approximately 50 micrograms/kg. Gross pharmacological tests of antx-a(s) on isolated chick biventer cervicis and frog rectus abdominis muscles showed no direct agonistic effect. Instead, antx-a(s) augments the acetylcholine response and antagonizes the actions of d tubocurarine. Twitch potentiation and tetanic fade were observed on isolated rat phrenic nerve--diaphragm muscle when stimulated indirectly at different frequencies. In acute toxicity tests with mice and rats the signs of poisoning were indicative of excessive cholinergic stimulation. Mice pretreated with atropine sulfate showed longer survival times and no parasympathomimetic signs of toxicity. The mice still died of respiratory arrest with convulsions, which indicated that toxicity is due to more than just the peripheral muscarinic action of antx-a(s). Assays of serum cholinesterase of rats in acute toxicity tests showed complete inactivation of the enzyme at doses of 350 and 600 micrograms/kg. It was concluded that antx-a(s) may be acting as an anticholinesterase, thereby causing toxicity. PMID- 3087031 TI - Antigenic relationships between Mojave toxin subunits, Mojave toxin and some crotalid venoms. AB - Immunochemical responses of a number of pit viper venoms to antibodies derived separately from the acidic and basic subunits were investigated by enzyme linked immunosorbent assay (ELISA) and Ouchterlony immunodiffusion. The polyclonal antisera to the basic subunit were generated in rabbits, whereas mouse hybridoma cell cultures were used to produce antibodies to the acidic subunit. The immunochemical response of a venom correlated well with published values for LD50 dose for the test venom. Many venoms that elicited a positive response with antiserum to the basic subunit also reacted strongly with the hybridoma derived antibodies to the acidic subunit. The data support the conclusion that crotalid venoms which are more lethal have in common a potent venom component that is immunochemically related to Mojave toxin. PMID- 3087032 TI - Detoxification of the T2 fraction from a scorpion (Tityus serrulatus, Lutz and Mello) venom by iodination and some immunogenic properties of the derivatives. AB - The iodination of the T2 fraction abolished its lethal capacity, and doses up to 30 times the LD50 were injected i.p. in mice without noticeable toxic effects. The modified fraction retained its immunological properties. Antibodies generated against the iodinated T2 fraction were also reactive toward the native T2 fraction, T1 fraction and the whole soluble venom. PMID- 3087033 TI - Lethal potency and tissue distribution of 125I-labelled toxic peptides from the blue-green alga Microcystis aeruginosa. AB - Toxic heptapeptides from a water bloom of the cyanobacterium Microcystis aeruginosa were purified by HPLC. The unoxidised fraction was iodinated with 125I plus 127I by the lactoperoxidase/H2O2 method, further purified by HPLC, and the non-iodinated and three iodinated fractions administered i.p. to male mice. All iodinated fractions were toxic, with symptoms and pathological lesions of the liver identical with those caused by non-iodinated peptide. Radioactivity was concentrated in the liver of mice at death. PMID- 3087034 TI - Preliminary studies on the venom of the Chinese snake Azemiops feae, Boulenger (Fea's viper). AB - Fea's viper (Azemiops feae) produces a venom which is highly toxic to mice when injected by the s.c. or i.v. routes. The i.v. LD50 of Azemiops venom for Swiss Webster laboratory mice is 0.52 mg/kg. Azemiops venom produces no hemorrhagic activity in mice or rabbits. Immunodiffusion indicates that some fractions of Azemiops venom are antigenically related to viperid, elapid and crotalid venoms. SDS-PAGE electrophoresis reveals that this venom contains as many as 22 proteinaceous components. PMID- 3087035 TI - Stabilization of fluorochromes after immunofluorescent staining of tissue and embedding in Epon. AB - Tissue blocks or sections immunofluorescent stained before embedding, i.g., liver and kidney, can be stored for more than 3 years without demonstrable fluorescence decay. The processing steps, including poststaining dehydration by alcohols and embedding in expoxy resins, seem to stabilize the fluorochromes fluorescein isothiocyanate (FITC) and tetramethylrhodamine isothiocyanate (TRITC) so that they fade less during illumination. This is an advantage of the pre-embedding, immunofluorescent staining technique which is combined with a lack of damage to the antigens by the plastic embedding medium. PMID- 3087036 TI - The economics of caring: challenges and new opportunities for nursing. PMID- 3087037 TI - A fresh look at ophthalmia neonatorum. AB - Recent surveys have stressed the importance of Chlamydia trachomatis as a cause of ophthalmia neonatorum. Advances in diagnostic techniques should enable this organism to be readily identified. Precise identification of the aetiological agent is important because of the differing antibacterial sensitivities of the pathogens. Neisseria gonorrhoeae and C. trachomatis require systemic therapy. Investigation and treatment of both parents is necessary to prevent recurrence in subsequent pregnancies. PMID- 3087038 TI - The effect of hyperglycemia on isolated rodent islets transplanted to the kidney capsule site. AB - The effect of hyperglycemia on transplanted rat pancreatic islets was studied using a new technique for transplanting a defined number of islets in a blood clot. Normal or streptozotocin-diabetic DA rats were given 400 DA islets under the left kidney capsule (a number shown to be insufficient to reverse diabetes). After 2 weeks the diabetic rats were given a further 1000 islets under the right kidney capsule to reverse diabetes. Kidneys from both groups were examined at 2 weeks after the initial islet implant and at 3 months for both gross and histological appearance and for insulin content. After 2 weeks left kidneys from nondiabetic rats showed abundant islet tissue, with an insulin content of 116 (+/ 14 SEM) milliunits, compared to 1 +/- 0.5 milliunits in the right kidney. Kidneys from diabetic rats showed no islets recognizable grossly. Histological examination showed vacuolated tissue scarcely recognizable as islet tissue, and the insulin content of the left kidney was reduced to 18 +/- 5 milliunits. However, 3 months after reversal of diabetes by transplantation of 1000 islets to the right kidney, histologically "normal" islet tissue was again visible on the left kidney, and the insulin content was 160 +/- 36 milliunits. Islets left in normal animals for 3 months contained 195 +/- 50 milliunits. These experiments show that islets implanted beneath the kidney capsule in diabetic rats are not destroyed by two weeks hyperglycemia. This suggests that protection of islets after implantation by insulin treatment is unnecessary, even in the presence of a persistently raised blood sugar. PMID- 3087039 TI - Relationship of interferon-gamma and neopterin levels during stimulation with alloantigens in vivo and in vitro. AB - We have recently shown that interferon-gamma is capable of activating the key enzyme of pterin biosynthesis in macrophages. This leads to excretion of the stable degradation product neopterin. In this article we present experimental evidence suggesting that stimulation of T cells by alloantigens is associated with release of interferon-gamma--which, in the case of rejection, is locally restricted and not always detectable in the bloodstream. Neopterin induced by this lymphokine, however, readily penetrates tissue barriers and is detectable in the serum. This conclusion is based on two different sets of observations: (1) If supernatants of MLCs are compared with sera from patients with documented acute rejection episodes for their interferon-gamma and neopterin levels, a marked gradient is observed to exist between interferon levels measured in vitro and in vivo; this is not the case for neopterin for which comparable levels were seen. (2) Detection of interferon-gamma in sera of allograft recipients invariably precedes an increase of neopterin; on the other hand, increasing neopterin counts are also seen in the absence of detectable interferon-gamma levels in the serum. It thus appears that although interferon-gamma release during allograft rejection is primarily restricted to the tissue, evaluation of certain metabolites of interferon-dependent metabolic pathways enables definition of its endogenous release. Whereas interferon gamma represents a less reliable marker in the monitoring of rejection episodes, it might offer an additional means to differentiate rejection from systemic infections. Such a discrimination can not be achieved with the neopterin marker. PMID- 3087040 TI - Pancreas transplantation--1985. PMID- 3087042 TI - [Mucopolysaccharidoses. Apropos of 25 cases in 17 families]. PMID- 3087041 TI - [Characteristics of the T-lymphocytes interacting with hematopoietic stem cells: the expression of Lyt-3 antigen]. AB - The lymph node cells were treated with monoclonal anti-Lyt-3 antibodies (anti-Lyt 3) and complement. Their interaction with colony-forming units (CFU) of bone marrow was studied. Anti-Lyt-3 did not affect the activity of T-lymphocytes, which changed the pattern of syngenic CFU differentiation in spleen of irradiated mice. On the contrary, the activity of T-lymphocytes, which inactivated proliferation and differentiation of non-syngenic CFU in spleen, was decreased. In the peritoneal cavity of irradiated mice antibodies did not affect the activity of T-lymphocytes which suppressed the colony-formation of non-syngenic stem cells and switched off the activity of T-lymphocytes that stimulated syngenic CFU colony-formation. The subpopulation characteristics of regulatory and effector T-cells has been analysed. PMID- 3087043 TI - [Dissolution of urate calculi]. PMID- 3087044 TI - [High-voltage roentgen therapy of cancer of the prostate]. PMID- 3087045 TI - [Tuberculosis of the prostate]. PMID- 3087046 TI - Paraganglioma of urinary bladder in patient with neurofibromatosis. AB - Pheochromocytoma in patients with von Recklinghausen's neurofibromatosis is a well-known association. However, extra-adrenal pheochromocytoma with this association is rare. Herein we report a case of urinary bladder paraganglioma in a patient with neurofibromatosis. PMID- 3087047 TI - Canine pregnancy and parturition. AB - In contrast to the large variation in canine gestation lengths based on mating-to whelping intervals (56 to 70 days), gestation length based on intervals from the preovulatory LH surge to whelping shows little variation (64 to 66 days). By considering the preovulatory LH surge as the central endocrine event of the fertile cycle, various events can be reasonably timed, including ovulation on day 2, oocyte maturation on day 4, reduced fertility after day 6, implantation around day 17, and development of fetal radiopacity after day 45. Throughout pregnancy, gestation is dependent on ovarian progesterone secretion and, thus, on pituitary LH and prolactin for luteotrophic support. Because prostaglandin F2 alpha is luteolytic in the bitch, it may be involved in the luteolysis observed immediately prepartum in association with rises in maternal cortisol and prolactin levels. PMID- 3087048 TI - Use of anticonvulsants in small animals. PMID- 3087049 TI - The vaginal mucus agglutination test in the diagnosis of bovine brucellosis. AB - Of 1140 vaginal mucus agglutination tests (VMAT) on specimens obtained in 1971-72 from 663 dairy cows in seven herds infected with brucellosis, 97 were positive. When the VMAT was positive one or more serological tests were also positive. Of the 97 corresponding serum agglutination tests 80 sera had titres of more than 533 international units. Only 69.8 per cent of VMAT from serologically positive cows were positive. No evidence was found of non-specific agglutinins in vaginal mucus and positive VMAT reactions appeared to be specific for field infection. Three cows showed evidence of local agglutinins in the vagina. Hence herd testing by VMAT has no advantage over tests of blood serum but the test could be an aid in establishing whether individual cattle are infected. PMID- 3087050 TI - A simple epidemiological method for animal trypanosomiasis to provide relevant data for effective financial decision-making. AB - The epidemiology of bovine trypanosomiasis on Galana Ranch, Kenya was studied for one year (July 1980--June 1981), using measurements from an experimental population of 3 types of Boran cattle. The results were applied to the estimated ranch population at risk, and an attempt was made to measure the potential economic loss due to trypanosomiasis. The potential losses in beef production due to trypanosomiasis in the ranch population at risk at Galana were estimated at around K.Shs. 8900/km2, when the stocking rate was 14.2 Tropical Livestock Units per km2. The estimated potential loss in the total population at risk was approximately K.Shs. 5 million (around US$ 700,000 at 1981 values). These losses can be minimised by good management techniques based on accurate epidemiological information. Results indicated that Orma-type Boran steers are more resistant to trypanosomiasis than Galana-type Boran steers. Although both types showed similar mortality rates, untreated Orma animals which survived showed a similar growth performance to animals maintained under 3-month Samorin prophylaxis. Untreated Galana Borans lost 14% of their body weight when compared with animals maintained under 3-month Samorin. Also, 30% of the untreated Orma Borans never showed trypanosomes in their blood over the study period, while all corresponding Galana Borans showed parasites; this resulted in a lower measured attack rate in Orma cattle. In 1982, a combination of treating only those animals under trypanosome attack, relating the timing of chemotherapy to measured increased trypanosome attack, and the increased utilisation of the trypano-tolerant Orma Borans resulted in an annual saving of around US$ 110,000 in control costs and an increased land usage of approximately 5%. PMID- 3087051 TI - [Giant bifurcate esophageal diverticulum simulating a malignant lung tumor]. PMID- 3087052 TI - Neoplastic plasma cells in follicular lymphomas. Clinical and pathologic findings in six cases. AB - Six cases of follicular lymphoma contained an abundant plasma cell component. With immunoperoxidase techniques, this was found to demonstrate monotypic cytoplasmic marking for either K or L Ig light chain in five cases, and for IgA heavy chain only in one case. A histogenetic relationship between follicular center cells and plasma cells was suggested by cell forms morphologically intermediate between these two types and by monotypic plasma cells in the neoplastic follicles. The progressive differentiation of follicular center cells into Ig-secreting cells in these cases is likely to be the result of an alteration of the immunoregulatory mechanisms that usually block the differentiation of follicular lymphomas. Four of our patients presented with disseminated disease, three had extranodal presentation and four manifested serum paraproteins. Their median survival was 40 months; two of them died of disease. The published data and our own suggest that follicular lymphoma with plasmacytic differentiation is a malignancy of intermediate grade, with survival and clinical features closer to lymphoplasmacytic/lymphoplasmacytoid lymphoma (LP immunocytoma) than to follicular lymphoma. PMID- 3087053 TI - Paragranuloma is a variant of Hodgkin's disease with predominance of B-cells. AB - Fifteen cases of Hodgkin's disease of nodular and diffuse paragranuloma subtype (nodular and diffuse subtype of lymphocyte predominant type of Hodgkin's disease) were studied by light and electron microscopy, using monoclonal antibodies recognizing T and B-lymphocytes and dendritic reticulum cells. The results were compared with findings on 10 cases of Hodgkin's disease of mixed type with lymphocyte predominance. The present study provides evidence that paragranuloma represents a special variant of Hodgkin's disease different from other subtypes. Paragranuloma is characterized by predominance of B-cells which were demonstrated with a new B cell reagent KiB3 on routinely processed paraffin sections. PMID- 3087054 TI - Immunocytochemical characterization of lymphocytes in benign and malignant lymphocyte-rich serous effusions. AB - The cytological diagnosis of malignant Lymphoma in serous effusions can be difficult because reactive lymphocytes may be morphologically indistinguishable from malignant cells in lymphocytic and other low grade Non-Hodgkin's lymphomas. As a result of the present study, diagnostic accuracy can be improved by means of B- and T-cell enumeration using an immunoalkaline-phosphatase method (IAP). 30 cytological specimens, including 28 pleural, 1 pericardial and 1 ascitic fluids, were studied with a panel of monoclonal anti B- and anti T-cell antibodies (PAN B, kappa, lambda, T1, T2, OKT4, T8). Reactive lymphocytic effusions were characterized by a predominance of T cells constituting greater than or equal to 80% of all lymphocytes with an excess of helper/inducer cells (mean helper to suppressor ratio 3.0) and by a surface kappa to surface lambda ratio of 1.6 on B cells. Tuberculous effusions showed a similar distribution of lymphocyte subpopulations whilst most of the carcinomatous fluids showed a lower percentage of T cells (lowest value 67%) and lower Th: Ts ratio (mean 2.0). Lymphoid cells in samples of five B-cell lymphomas were characterized by T-cell depression (less than 70%). B-cells in three cases expressed clear cut light chain monoclonality which was at least suggested in the other two cases. Lymphoid cells from two cases of Hodgkin's disease expressed an indistinct immunological pattern. Labelling of cytoplasmic immunoglobulins (heavy and light chains) using the peroxidase antiperoxidase method (PAP) may be important to characterize neoplasms of the plasma cell series. It is concluded that the chosen panel of antibodies in combination with IAP labelling method may be of great value in identifying B-cell lymphomas. The technique can be used in the routine laboratory and storage of unlabelled and labelled slides over long periods is possible. PMID- 3087055 TI - Tumour of Wagner-Meissner touch corpuscles. Wagner-Meissner neurilemmoma. AB - Two benign tumours composed mainly or exclusively of Wagner-Meissner corpuscles are described. In the first case the touch corpuscles are composed of closely piled laminar cells and surrounded by argyrophilic fibres. In the second case some Schwann cells are observed in between the tactile corpuscles. The light microscopic, electron-microscopic and immunohistochemical results demonstrate that these corpuscles are comparable with the tactile end organs of the skin. Immunohistochemically, neuron-specific enolase, vimentin and protein S-100 could be demonstrated in the tactile corpuscles. Neural processes present in normal Meissner corpuscles are absent and immunohistochemically no nerve fibres or nerve endings can be demonstrated using antibodies to neurofilaments as they are observed in normal touch corpuscles of the skin. Tumours which consist mainly of multiple touch corpuscles have not been described in the literature. It is suggested to call these tumours Wagner-Meissner neurilemmoma. PMID- 3087056 TI - Splenic erythropoiesis in rats under hypoxic and post-hypoxic conditions. AB - In rats chronic hypoxia causes extramedullary haematopoiesis mainly localized in the spleen. It is not known how splenic erythropoiesis develops and how it regresses after termination of hypoxia. In this study the spleen of rats exposed to chronic hypoxia was studied by light and electron microscopy; the findings were compared to relevant peripheral blood values. Splenic erythropoiesis begins almost immediately after exposure to hypoxia and reaches its maximum after 2-4 weeks. It occurs mainly in the splenic cords drawing upon local erythroblasts and is accompanied by an increase in splenic weight as well as a decrease in splenic iron stores. After termination of hypoxia marked phagocytosis by splenic cord macrophages diminishes the number of erythroblasts and of erythrocytes with a concomitant increase in splenic iron stores. Thus, splenic erythropoiesis appears to be inhibited as part of a rebound phenomenon and returned to normal by phagocytosis of erythroid cells within 4 weeks after cessation of the hypoxic stimulus. PMID- 3087057 TI - Pathohistological and immunohistochemical studies on Castleman's disease of the lymph node. AB - Histological and immunohistochemical examinations were carried out on lymph nodes in 9 cases with Castleman's disease. In all cases, there were whorled follicle centers and proliferation of blood vessels. These findings were also considered to be important criteria for diagnosis of the plasma cell type of this disease. The whorled follicle centers often consisted of smaller concentrical structures and contained factor VIII-positive cells. In some cases, there were many small whorled structures surrounding postcapillary venules within the interfollicular areas of lymph nodes. These structures had factor VIII-positive granules indicating their endothelial origin. In 2 cases of the plasma cell type, monoclonal plasma cell proliferation (IgA, lambda and IgG, lambda, respectively) and cellular atypia were identified. These findings showed that extramedullary plasmacytoma could occur not only in the multicentric form, but also in the solitary form of Castleman's disease. In the lymph node of a case of the hyaline vascular type, there were scattered tumour nodules consisting mainly of factor VIII-positive, atypical spindle cells suggesting associated Kaposi's sarcoma. It is conceivable that an abnormal immune state plays a role in pathogenesis of Castleman's disease. PMID- 3087059 TI - A fly, Drosophila melanogaster, forms 11-cis 3-hydroxyretinal in the dark. AB - All-trans and 11-cis 3-hydroxyretinals were synthesized and the presence of these substances in the head of Drosophila melanogaster was shown by using high performance liquid chromatography. Even when the head extract was prepared in the dark from the flies reared successively in the dark, both of the 3-hydroxyretinal isomers were detected. In the culture medium, they were not present. D. melanogaster must have an 11-cis 3-hydroxyretinal forming-system that does not need light. PMID- 3087060 TI - Frozen recovered red cell boosting of female donors for anti-D-production. AB - A selected group of women previously immunized in pregnancy by the Rh(D) antigen were boosted with 0.5 ml of Rh(D)-positive frozen recovered red cells from an accredited donor panel. The response was prompt and sustained and increased the anti-D content by almost 10-fold. In spite of the reduced rate of clinical immunisation to the Rh(D) antigen, it was possible to recruit females with anti D, acquired in pregnancy, for secondary boosting and a programme is recommended which maximizes efficiency and safety. PMID- 3087058 TI - Aphidicolin-resistant mutants of bacteriophage phi 29: genetic evidence for altered DNA polymerase. AB - Aphidicolin-resistant mutants (Aphr) of Bacillus subtilis bacteriophage phi 29 were isolated after mutagenesis with hydroxylamine. Efficiency of plating (e.o.p.) of the resistant mutants was not reduced at 500 microM aphidicolin, although e.o.p. of wild type phi 29 was less than 10(-5) at the same concentration of aphidicolin. By recombination and complementation analyses, both sites of the mutations, aph-71 and aph-101, of Aphr71 and Aphr101, respectively, were mapped in gene 2 which encodes phi 29 DNA polymerase. The activity of wild type phi 29 DNA polymerase, in a partially purified fraction, was inhibited by aphidicolin. DNA polymerases from Aphr71 and Aphr101, prepared in the same manner as that of wild type, were resistant to the drug. These results indicate that the acquisition of the aphidicolin resistance of Aphr71 and Aphr101 of bacteriophage phi 29 results from a structural alteration of phi 29 DNA polymerase which reduces sensitivity to aphidicolin. PMID- 3087061 TI - [Determining the bactericidal effects of drugs and blood serum on opportunistic bacteria]. PMID- 3087062 TI - [Combined use of levomycetin and ampicillin in patients with abdominal typhus and paratyphoid fever]. PMID- 3087064 TI - [Combined use of training on a bicycle ergometer and sustak in stenocardia]. PMID- 3087063 TI - [Use of repeat courses of unithiol in the complex treatment of liver cirrhosis]. PMID- 3087065 TI - [Immunoglobulins in the serum of chronic pyelonephritis patients]. AB - The authors studied the serum levels of immunoglobulins G, A and M in 72 patients with chronic pyelonephritis and 77 clinically healthy subjects. In spite of the high biological variability of the indices studied, high serum levels of IgG and IgA were established in the patients with active urologic infection and with advanced renal insufficiency. Significantly higher values of IgG were established in active pyelonephritis, caused by E. coli and Proteus and of all immunoglobulins--in infection with Enterococcus. The serum level of immunoglobulins in chronic pyelonephritis should be complexly interpreted, together with the other clinical and laboratory data. PMID- 3087066 TI - [Diseases of the Achilles tendon]. AB - In this report diseases of the Achilles tendon are discussed. First an anatomical survey of this region is presented including anatomical variations together with the results of the author's own investigations on corpses. Certain positions and insertions of the plantaris tendon with respect to the Achilles tendon may have pathological influence. Pathological aspects are discussed after a review of the physiology of the Achilles tendon, including functional and tensile tests. The clinical picture changes according to the location of the pathological disorder- tendon, paratenon, insertion and bursae--and whether the disease is acute or chronic. There are various reasons for degenerative changes in the tendon, which can even lead to rupture. Surgical and non-surgical treatment and their indications are presented. In conclusion treatment methods and their results for 36 cases are given. PMID- 3087067 TI - Evaluation of certain food additives and contaminants. Twenty-ninth Report of the Joint FAO/WHO Expert Committee on Food Additives. PMID- 3087068 TI - 3,3',4,4'-tetrachloro[14C]biphenyl in pregnant mice: enrichment of phenol and methyl sulphone metabolites in late gestational fetuses. AB - The distribution of radioactivity after injection of 3,3',4,4' tetrachloro[14C]biphenyl (14C-TCB) in pregnant mice was determined by autoradiography and computer-assisted densitometric analysis. TCB metabolites in fetal tissue were analysed by g.l.c. and g.l.c.-mass spectrometry and compared to the synthesized reference compounds 2-, 5- and 6-methoxy-3,3',4,4' tetrachlorobiphenyl. The concentration of radioactivity was high in the uterine fluid, and in the fetuses in late gestation. Fetal radioactivity decreased after pretreatment with a high dose of unlabelled TCB. Radioactivity was reversibly bound to fetal tissues. A phenolic metabolite, 3,3',4,4'-tetrachloro-2 biphenylol, and a methylsulphonyl-tetrachlorobiphenyl were found in fetuses in late gestation. No unmetabolized TCB was detected in the fetuses. PMID- 3087070 TI - [Current status of neonatal hemolytic disease caused by Rh incompatibility]. PMID- 3087069 TI - Comparison of cytochrome P-450 content and activities in liver microsomes of seven animal species, including man. AB - The cytochrome P-450 content found in human livers obtained post mortem was between 0.21-0.42 nmol/mg protein. The kinetic parameters of the mono-oxygenase activities--Km and Vmax--were determined in liver microsomes for N-demethylation (aminopyrine, benzphetamine, ethylmorphine), O-demethylation (4-nitroanisole), O deethylation (7-ethoxycoumarin) and hydroxylation (benzo[a]pyrene), in an attempt to establish an inter-species comparison between man and the six animal species studied. The four substrates studied (aminopyrine, benzphetamine, ethylmorphine, benzo[a]pyrene) were shown to be less active in humans than the male rat, which is the most commonly used model. However, other animal species, such as the female Sprague-Dawley rat and the pig, are much more similar to man. From a procedural point of view, the optimal substrate concentrations vary from one experimental species to another. Due to the apparent Km observed, for example, the activities of the guinea-pig require a higher substrate concentration. PMID- 3087071 TI - [Anesthetic procedures in endoscopic interventions of the respiratory system]. AB - Choice and application of anaesthesia in patients undergoing endoscopies of the airways have to take into consideration several specific aspects, starting with preanaesthetic investigation and premedication. On principle local anaesthesia may be administered as well as general anaesthesia or a combination of both. Using modern forms of general anaesthesia, optimal oxygen supply, sufficient carbon dioxide elimination, complete muscle relaxation and good sleep induction conditions can be provided. On the other hand reduction of reflex activity and analgesia are to be improved. The importance of a well trained and experienced anaesthetist and careful intra- and postanaesthetic supervision of the patient is emphasized. PMID- 3087072 TI - [Anesthesiologic problems in endoscopic interventions of the respiratory organs]. AB - In 28 patients--16 normotensive and 12 hypertensive patients--anaesthetized with hexobarbitone, halothane, nitrous oxide/oxygen and intermittent doses of suxamethonium we examined the influence of diagnostic bronchoscopy on arterial blood pressure, heart frequency, rate pressure product as well as acid-base balance and arterial oxygen partial pressure. Both groups of patients showed a remarkable and highly significant increase in these hemodynamic parameters during intubation, extubation and bronchial lavage. Clinically relevant changes of acid base balance and arterial oxygen partial pressure which could be responsible for these hemodynamic reactions did not occur. Sympathicotonic reflexes caused by the bronchoscopy are considered to be the main causes for the increase in blood pressure, heart frequency and rate pressure product. They can only be prevented by a sufficient narcosis depth. PMID- 3087073 TI - [Behavior of pressure and flow parameters of pulmonary circulation in bronchologic studies in general anesthesia using 2 injectable anesthetics]. AB - Flow- and pressure-parameters of the pulmonary circulation were measured in the course of bronchologic investigations under general anaesthesia using as narcotics in group I (n = 14) Hexobarbital, in group II (n = 10) Propanidid (Sombrevin). The increase of mean pulmonary artery and mean PCW-pressure in group II is significantly higher than in group I. This seems to be caused by a more reduced myocardial function due to Sombrevin. Heart rate and pulmonary vascular resistance increase in both groups uniformly. The pO2 is markedly reduced up to 4 hours after the investigation accompanied by an increase of pCO2. PMID- 3087074 TI - [Injector ventilation in direct laryngoscopy]. AB - A newly-developed apparatus system for injector-ventilation is described, which consists of the main parts of the modified respirator and the injector-tube. After laboratory and clinical tests this system regularly finds application in direct laryngoscopy--diagnosis and microsurgery--of laryngeal diseases. In the technique described the jet-pump-effect is made use of, contrary to the jet ventilation which is based on the principle of the free jet. Depending on the tasks to be solved the standard laryngoscopes by Kleinsasser as well as those by Brandt can be used. According to our experiences, that have so far been obtained in more than 250 patients, the method of the injector-ventilation guarantees sufficient ventilation. PMID- 3087075 TI - [Unwanted modification of the thyroid gland by drugs with special reference to nonsteroidal antirheumatic agents]. AB - In two retrospective clinical studies was investigated the influence of the modern non-steroidal antirheumatic drugs indometacin and diclofenac (Rewodina) on the thyroid gland and corresponding peripheral hormone parameters. Under longterm treatment with indometacin a moderate strumigenic effect could be observed, which could not clearly be proved under the diclofenac therapy. In all patients with rheumatoid arthritis, independent of the kind of pharmacotherapy, decreased T3 hormone levels were found in normal serum T4-values. The findings are discussed as "low-T3-syndrome" in rheumatoid arthritis, induced by the disease lasting for many years possibly in combination with the long-term therapy with antirheumatic drugs. In a second series of investigations in 75 out of 3,104 patients (2.4%) with a bland struma distinct references to a medicamentous evocation of the enlargement of the thyroid gland were found. Anticonvulsive drugs and the antidepressive drug lithium stood in the first place as inductors of such medicamentous struma. Of the non-steroidal antirheumatic drugs only some cases could be ascribed to phenylbutazone, whereas the more modern preparations indometacin and diclofenac in none of our patients could with certainty be made responsible for a development of struma. PMID- 3087076 TI - [Gabexate mesilate in the treatment of acute pancreatitis. Results of a Hannover multicenter double-blind study with 50 patients]. AB - We investigated the effect of a new synthetic protease- and phospholipase A2 inhibitor gabexate mesilate (FOY) in a multicenter (6 hospitals in Hannover and vicinity) double-blind study on the clinical course of acute pancreatitis. 50 patients were randomized into two subgroups. One group was treated with 3 X 300 mgs of gabexate mesilate per day for 9 days as a continuous intravenous infusion, the control group received placebo. There was no difference in these two groups regarding age and sex, but there was a discrepancy concerning the severity (stage I-IV) of the acute pancreatitis at the onset of treatment. More of the patients in the gabexate mesilate-group had severe disease on admission to hospital. Of the 7 patients (14%) who died, 5 were in the gabexate mesilate-group whereas only 2 were in the placebo group. This difference in the mortality rate is not significant. There was, however, a significant difference at the 5% level between the verum-group and the control group concerning the decline in alpha-amylase activity in serum and the number of complications. The difference was greatest in alcohol induced acute pancreatitis. A non-parametric test showed a significant reduction in hospitalisation time in the gabexate mesilate-group. Due to the small number of patients and the inhomogeneous clinical course of the acute pancreatitis a definite conclusion concerning the effect of gabexate mesilate on the clinical course of acute pancreatitis is not possible. Further studies with a much greater number of patients and more homogeneous groups with respect to the severity of the acute pancreatitis at the onset of the therapy with gabexate mesilate or placebo are necessary. PMID- 3087077 TI - Comparison of two Egyptian strains of Schistosoma mansoni in hamsters. AB - In human infection with Schistosoma mansoni from Beni-Suef, the eggs were encountered more frequently in the urine of patients than in infection with S. mansoni from Giza, where eggs were passed into the stool. A comparative study of the two strains of S. mansoni from Beni-Suef and Giza has been carried out in golden hamster. Consistent strain differences were observed. The Beni-Suef strain proved to have lower worm recovery and different egg distribution patterns in tissues of infected hamsters. Worms of both sexes of this strain were larger in size and required a longer period to reach maturity. Hence, the prepatent period was prolonged. Significant differences between the two strains were also noted in the number of eggs per worm. A lower mortality rate and a longer survival time were encountered in hamsters infected with the Beni-Suef strain. PMID- 3087078 TI - [Disease picture of dysplasia epiphysealis hemimelica]. AB - Dysplasia epiphysealis hemimelica - an epiphyseal developmental disturbance of the skeleton - is combined with exostose-like, tumor-simulating cartilaginous hypertrophy of bone tissue, mainly located at the epiphyses of the lower extremities and at the tarsal bones. In the case of multiple involvement the unilateral type prevails (hemimele type); within the epiphyses it is mostly the medial part which is undergoing changes. Rare sites are patella, head of the hip bone, shoulder joint, carpalia, more commonly affected are talus as well as other tarsal bones, distal femoral epiphysis and proximal and distal tibial epiphysis. Histologically, dysplasia epiphysealis hemimelica is identical to cartilaginous exostosis. Bone formation is taking place by enchondral ossification (epiphyseal osteochondroma). The ratio between male and female is 3:1. As a rule, this disease becomes manifest in early childhood or adolescence by indolent swellings of the joint region, restricted movement, axis shift, sometimes by differences in the length of the legs. Therapeutic guidelines are not unanimous. On one hand, correction osteotomy is not recommended until the completion of growth, while on the other hand excision of the cartilaginous hypertrophy in early childhood (before the age of 4) is postulated. Since there are less than 100 cases described in literature, another 8 cases of this extremely rare disease are to be presented here. PMID- 3087079 TI - [Sprouting of brain neurons and the phenomenon of intercellular recognition in memory processes]. PMID- 3087080 TI - [A case of familial neurofibromatosis]. PMID- 3087081 TI - [A case of delayed diagnosis of leprosy]. PMID- 3087083 TI - [Effect of simultaneous isorhythmic stimulation of the mammillary bodies and septum on the rate of formation of a defensive conditioned reflex to light in the rabbit]. PMID- 3087082 TI - [Neuronal mechanisms of goal-directed behavior in the monkey]. PMID- 3087084 TI - Organochlorine pesticides and polychlorinated biphenyls in livers of cod from the southern Baltic, 1983. AB - Hexachlorobenzene (HCB), alpha-, beta-, gamma- and delta-benzenehexachloride (BHC; HCH), p,p'-DDE, o,p'-DDD, o,p'-DDT, p,p'-DDD and p,p'-DDT (sigma DDT) and polychlorinated biphenyls (PCB) levels have been determined in livers of 210 cod (Gadus morhua) netted during 1983 in a different regions in the southern part of the Baltic Sea. The mean levels found for cod livers related to wet weight (mg/kg) were: 0.096 HCB, 0.15 alpha-BHC, beta-BHC was found in trace amounts, 0.098 gamma-BHC, delta-BHC remained undetected, 0.26 sigma BHC, 1.1 p,p'-DDE, o,p'-DDD and o,p'-DDT remained undetected, 1.1 p,p'-DDD, 0.39 p,p'-DDT, 2.6 sigma DDT and 7.2 PCB. The levels of sigma DDT, sigma BHC and HCB found are comparable with those noted in livers taken from cod of the same length class and netted in 1981, whilst-for PCB somewhat lower levels were found. Because of heavy contamination with PCBs, sigma DDT, sigma BHC and HCB the livers of cod caught in Baltic Sea still remain insuitable for human consumption. PMID- 3087085 TI - [Methodological framework of the evaluation of systematic screening and treatment of preexistent lesions of the colon and the rectum]. AB - Among the conditions which need to be filled when generalizing the mass screening of polyps in view of the secondary prevention of colorectal cancers, three are already present: 1) it is a frequent and serious cancer; 2) there is an affiliation between benign tumours and cancer; 3) an effective non-mutilating treatment of benign tumours is available. On the other hand, two additional conditions remain unfilled and yet lie within the domain of research by methodologically rigorous studies: the setting up of a screening test with a high cost-effectiveness relationship; the epidemiological demonstration of the decreasing incidence of colorectal cancers following screening and treatment of precancerous lesions. PMID- 3087086 TI - [Occupational medicine preventive studies in West Germany]. AB - Prevention is of increasing importance in medicine, particularly in occupational medicine. The programs of health surveillance at the workplace in the Federal Republic of Germany are discussed. In 1983, 1,400,000 examinations of employees were performed; exclusion criteria were fulfilled in 2.1% (0.9% only temporarily). In 1984 the respective numbers were 1,450,000 examinations (1.8%, 0.8%). During the last few years, health surveillance programs markedly have improved the efficiency of prevention of occupational diseases. They will be an important task for occupational physicians in the future. PMID- 3087087 TI - [Possibilities and limits in the treatment of cystine calculus diathesis with high-dose ascorbic acid. Results of a combined study with 17 patients]. AB - 17 cystine stone patients were treated with high doses of ascorbic acid (5 g p. d.). During the observation period, a total of only two natural passages of cystine stones could be observed. For five patients the therapeutic strategy was altered because the recurrence rate did not change and the cystine concentration in the urine was enhanced. One mixed calcium-oxalate/cystine stone had to be resected. In this case as well as on the occasion of further medical check-ups of other patients, an increased risk of calcium-oxalate stone formation was signalled by an enhanced oxalic-acid concentration in the 24-hour urine. Changes in blood serum and impairment in hepatic and renal functions were not observed. With three patients, the therapy had to be interrupted because of gastritis symptoms. The use of high-dose ascorbic acid therapy is recommended and is continued. In special cases, an additive of low do ses of alpha-mercaptopropionyl glycine is recommended. PMID- 3087088 TI - [Silver impregnation of connective tissue. 4]. AB - A method for silver impregnation of connective tissue is proposed which utilizes a physical developer instead of the traditional approach using successive treatments with ammoniacal silver solution and formalin. PMID- 3087089 TI - [Surgical treatment of Crohn disease and ulcerative colitis in standardized conditions]. AB - Crohn's disease and colitis ulcerosa are marked by a high periintestinal infection rate as well as catabolism with negative protein balance. To eliminate these factors the principle of withdrawing the intestinal function has been applied. Patients are put on a completely absorbable diet (2,500-3,500 kcal/d) using a thin duodenal (or jejunal) tube for 4-6 weeks. Depending on the initial condition, assistant or total parenteral nutrition is performed. - 203 patients with Crohn's disease (n = 154) or colitis ulcerosa (n = 49) underwent elective surgery from January 1st, 1978 to April 30th, 1985. Using the preparation of withdrawing the intestinal function 85.7% of the patients have had an uncomplicated postoperative course. Septic complications were found in 12.8%, non septic in 1.5%. The rate of mortality was 1.0%. In the case of Crohn's disease complications occurred in 10.4%, mortality was 0.6%. PMID- 3087090 TI - [Change in the diagnosis and therapy of Stein-Leventhal syndrome]. AB - Within the period from 1959 to 1984 the development of diagnostic and therapeutic possibilities has been demonstrated in 68 cases of women with a Stein-Leventhal syndrome. In the first group consisting of 11 female patients who were under examination until 1975 the clinical aspects took the leading part in the diagnosis. The ovarian wedge resection meant histological security and therapy at the same time. During the second period until 1980 (26 women) the hormone diagnostics was an essential criterion. The conservative therapy with Clostilbegyt aimed at the correction of these hormonal dysfunction as well. During the last years (31 women) diagnosis has been concentrated on etiological aspects. Correspondingly an individualized therapy was practised. The advances in the medical attendance of infertility become evident in the increase of the pregnancy rate from 9.1 to 61.3%. PMID- 3087091 TI - [Oral long-term tocolysis of threatened premature labor using clenbuterol (Contraspasmin, Spiropent). A placebo-controlled double-blind method]. AB - In quest of a efficacious oral tocolysis drug for inhibition the preterm labour we used in a randomised study the betamimeticum Clenbuterol or placebo with 1 tablet 3 times daily (3 X 0.02 mg/d Clenbuterol) in a total number of 109 patients. In result we can't see any significant distinction in gestational age and birth weight at delivery time and in duration of therapy up to delivery between the two groups. For that reason we are of the opinion, that a fundamental influence of Clenbuterol on premature birth cannot be expected. PMID- 3087092 TI - [Sewage sanitation. Workshop. Kiel, 1984]. PMID- 3087093 TI - [Quantitative studies of fecal indicators in various purification stages at two sewage purification plants in Schleswig-Holstein]. AB - In two sewage treatment plants, situated in Kiel (Bulk) and Plon, Schleswig Holstein, FRG, fecalcoliforms, totalcoliforms and enterococci were investigated as to quantity from October 1981 till November 1982. The number of the investigated bacteria varied widely during the whole investigation period. Showing the most distinct variations fecalcoliforms decreased in number, especially in December 1981 and January 1982. The majority of the samples yield bacterial numbers with the gradiation totalcoliforms greater than enterococci greater than fecalcoliforms. In the course of the purification process increasing variations of all bacterial parameters were found predominantly in the final settling tank. The possibility of influences induced by the input of catch pit's sludge is discussed. PMID- 3087094 TI - [Quantitative studies of Salmonella at two sewage purification plants in Schleswig-Holstein]. AB - Quantitative Salmonella counts in different stages of the sewage treatment plants of Kiel (Bulk) and Plon in Schleswig-Holstein (FRG) were measured during a one year-period. In weekly alternation the samples have been collected before and after each clarification step. Afterwards the Salmonella were analysed by a combined method (membrane-filtration, multistep enrichment, mpn). The inflows of the plants contained Salmonella in 98%. The treatment plant of Bulk reduced the Salmonella numbers around 89% while a reduction of 97% could be found at Plon. The most important step of the treatment for this reduction was the final sedimentation. The chemical precipitation at Plon declined the Salmonella numbers around further 87%. According to the seasonal fluctuations of the temperature of air and water the Salmonella values increased or decreased, respectively. This tendency was more impressive than it could be expected looking at the seasonal epidemiology of salmonellosis. In spite of the existing of separate sewerage systems in both towns rain led to increasing volumes of sewage. During the warmer period of the year this effect resulted in counts above average, while in wintertime - possibly caused by dilution and the salinity by roadsalt very low Salmonella numbers could be found in both treatment inflows. PMID- 3087095 TI - [Various Salmonella serotypes isolated at a sewage purification plant in a smaller city over a one-year period]. AB - A one-year-study was carried out in the waste-water treatment plant of Plon (population equivalents 60,000), which has a mechanical and a biological purification and an additional chemical flocculation. Samples were taken at five different places in the plant and examined for Salmonella by use of membrane filtration and MPN-method. 2,611 Salmonella-strains, representing 23 species, were isolated and serologically typed from samples taken at ten days. S. typhi murium was found most frequently (Table 1, Fig. 1). The largest spectrum of different types was located in the activated sludge-basin and at the outlet of the chemical flocculation (Table 2). No correlation could be established between the qualitative findings and the Salmonella-counts or other parameter like temperatures. All the ten species that have been officially reported to cause salmonellosis in man were also isolated from the sewage (Table 5). Findings of other Salmonella-serotypes are attributed to unreported human infections and animals or other sources. PMID- 3087096 TI - [Various Salmonella serotypes isolated at a sewage purification plant in a large city over a one-year period]. AB - The paper offers the results of a one-year-survey of Salmonella-serotypes in a municipal sewage-purification plant with a capacity of roughly 70,000 m3 per day. Findings of a quantitative study had shown Salmonella-maxima in the activated sludge-basin. This suggested specialized Salmonella-serotypes, resident in this part of the plant as a possible explanation which was to be verified by this study. On ten days samples were taken from the inlet, and the outlet of the primary-sedimentation-tank, the outlet of the activated-sludge-basin and the effluent of the final sedimentation-basin. A combination of membrane-filtration and MPN-Method with a fifefold enrichment in 2.5% tetrathionate was applied for salmonella isolation. Plating was done on malachit-green-chinablue-lactose-agar followed by serological typing. 1,587 strains representing 38 different serotypes (Table 1) were identified with S. typhi-murium (Fig. 1) accounting for 36% of the isolations followed by S. bovis-morbificans, S. hadar (Fig. 2) and S. panama. None of the serotypes found showed a preference of a special sampling point. The qualitative and quantitative distribution of Salmonella in the plant seems to depend on the Salmonella contents of the entering waste water mainly. The greatest variety of Salmonella-serotypes was located in the activated-sludge basin (Table 2) where oxygen-enrichment seems to result in the best ecological conditions for Salmonella survival. 3.3% of 722 strains examined did not produce hydrogen-sulphide (Table 3) and some showed damaged flagella-antigens. As a possible explanation toxic influences in the sewage are discussed. The epidemiological links between findings of Salmonella in sewage and in man of the same area are established and results differing in some aspects explained by the high rate of unknown infections. The existence of an autochthonous Salmonella population in the sewage plant could not be proved. PMID- 3087097 TI - [Quantitative studies of Salmonella in the sewage system of Kiel over a one-year period]. AB - In the course of 1983 the contents of salmonellae was investigated as to quantity in the Kiel sewage water system by samples taken off-hand every fourteen days. Determining the numbers of salmonellae by mpn-method the canalisation of the west side of Kiel fjord proved to be dominated by the abbatoir of Kiel-Wellsee. Additional evidence for that was given by the differing annual distribution of the numbers of salmonellae on the east-side of Kiel fjord. In total there was a remarkable reduction of salmonellae during the first and the fourth quarter of 1983 and a strong augmentation during summer. A reduction of salmonellae during the passage of the pump and pressure conduit-pipe, combining east- and west-side of Kiel fjord, could be seen. PMID- 3087098 TI - [Various Salmonella serotypes in the sewage system of Kiel over a one-year period]. AB - During one whole year (1983) Salmonella investigations were carried out in a total of 54 water samples taken from the sewage system of the town Kiel (FRG). Salmonella were present in 47 samples. 6181 strains were biochemically and serologically identified. The predominant serotypes isolated were S. typhi murium, S. panama, S. schwarzengrund and S. hadar. A correlation could be demonstrated between salmonella found in sewage and registered human excreters. PMID- 3087099 TI - [Microbiological and chemical studies of a water treatment plant with a wastewater pond containing plants during the winter of 1983-1984]. AB - First results of investigations in a small sewage plant (500 inhabitants) are presented. It has a special construction, since in addition to a trickling filter it is equipped with a waste water lagoon planted with marsh plants as a second biological treatment step. During the first winter after construction the BOD5 and the fecal indicator bacteria were reduced by 80% in the whole system. These values are comparable to those expected in conventional secondary treatment plants. The plant nutrients phosphate and ammonia were reduced far less by only 40%. Therefore additional investigations are planned for the next winter to show, whether the further development of plant roots within the pond will induce even higher reduction values. PMID- 3087100 TI - [Behavior of chlorinated solvents during mechanical and biological sewage treatment]. PMID- 3087101 TI - [Comparison of the bacterial population of the high- and low-power stages at a water purification plant]. PMID- 3087102 TI - [The problems of sludge build-up]. PMID- 3087103 TI - [Air-borne microbes in the vicinity of sewage treatment plants]. AB - Measurements of air-borne germs were conducted over one year at several sewage treatment plants with different loads and sewage treatment methods. The investigations were intended to show possible air-borne loads in the sewage treatment plants and their immediate vicinity, taking into account different climatic conditions. The results lead to the conclusion that neighboring residential areas or factories in the vicinity of sewage treatment plants are not exposed to air-borne hazards. PMID- 3087104 TI - [Emission of microorganisms from sewage treatment plants depending upon construction differences of single structural parts]. AB - In order to examine the influence exerted by the differing design of individual water treatment plant units on the emission rate of micro-organisms and the associated degree of exposure to which plant personnel is subjected, measurements were taken at three different types of treatment plants. Measurements were made using "Biotest" RCS Air Samplers. The total count of colonies was determined by means of Agar Strips GK-A (tryptic soy agar). Enterobacteriaceae were quantitatively ascertained using Agar Strips C (MacConkey agar), particular attention being paid to the determination of the coliform bacteria as faeces indicators. Agar Strips S (mannitol salt agar) were used to measure the count of staphylococci using Agar Strips HS (rosa Bengal streptomycin agar). Before taking measurements, the prevailing climatic conditions were recorded. It could be ascertained that the enclosure of the inflow area (screw conveyor pump station and aerated grit removal tank) lead to a considerable increase in the concentration of microorganisms in the air within the housing. The values dropped however, when adequate ventilation was provided. Differing oxygen in the activated sludge tanks - finebubble aeration at the tank bottom or the blowing in of air via centrifugal blowers - lead to large variations in the emission rates. However, the less the waste water is agitated, the lower the emission rates. In the case of fine-bubble aeration, rates which are also normally to be found in the "non-burdened" outside air were even recorded close to the aeration tank. In cases of centrifugal blower, the aeration tank should be covered with a shield. With this type of aeration the waste water is emitted radially towards the walls of the tank. The use of a sprinkler unit on an aeration tank equipped with centrifugal blower - to avoid foam formation on the surface of the water - does not lead to an increase in the already high emission rate. An increase in air pollution through mould fungi from waste water treatment plants could not be found. In conclusion, it can be said that different individual plant unit designs have a large influence on the concentration of micro-organisms in the ambient air of places of work of waste water treatment plant personnel. Emission rates can be limited to such a degree that, even in the immediate vicinity of the plant units, a decrease of micro-organism concentrations can be attained as comparable to the area outside the treatment plant. PMID- 3087105 TI - [Determination of colony count at 20 degrees C, 36 degrees C and 37 degrees C]. PMID- 3087107 TI - Effect of storage on acetylcholinesterase activity. PMID- 3087106 TI - Ultrastructure of granulomatous infiltrates in the small bowel in equine granulomatous enteritis. PMID- 3087108 TI - [Intermediate effects of orally administered zinc bacitracin. 1. Effect of tissue homogenates from rats premedicated with bacitracin on protein synthesis in rats]. PMID- 3087109 TI - [Intermediate effects of orally administered zinc bacitracin. 2. Effect of bacitracin fractions of protein synthesis in rats]. PMID- 3087110 TI - [Comparative studies on stallion sperm after repeated sperm collection and subsequent deep-freeze conservation]. PMID- 3087111 TI - Rectovaginal constriction in Jersey cattle. IV. Twenty-four hour urine hydroxyproline levels. PMID- 3087112 TI - Rectovaginal constriction in Jersey cattle. V. Electromyographic studies on the external anal sphincter muscle. PMID- 3087113 TI - [Osmotic resistance of erythrocytes in cattle]. PMID- 3087114 TI - Some biochemical physiological data of the Labrador retriever. PMID- 3087115 TI - [Mechanism of action of calcium antagonists on vascular smooth muscle]. PMID- 3087116 TI - [Catecholamine content in the wall of the thoracic duct of the dog during postnatal development]. AB - Studies have been made on the content of catecholamines (norepinephrine, adrenaline, dihydroxyphenylalanine) in the wall of the thoracic lymphatic duct of puppies during their first 3 months of postnatal life. It was found that within this period, the content of norepinephrine increases, that of adrenaline remains unchanged, whereas dihydroxyphenylalanine is detected only in animals of the first month. The increase in norepinephrine content indicates gradual maturation of the adrenergic innervation in the wall of the lymphatic duct. PMID- 3087117 TI - [Development of a latex agglutination method for the diagnosis of Pseudomonas aeruginosa infection]. AB - The present investigation has revealed the possibility of using different kinds of monodispersed polystyrene latex, produced in the USSR, as carriers in the process of the preparation of antibody diagnosticums intended for the detection of water-soluble slime antigens of Pseudomonas aeruginosa strains belonging to the most widespread serological types. The optimum conditions for the preparation of latex reagents and for making the latex-agglutination test have been experimentally established. The new diagnosticums+ have been shown to be highly species- and type-specific, which permits making judgment on the presence or absence of slime antigens of P. aeruginosa strains belonging to definite serovars in the clinical material under study. The preparations thus obtained have been found to retain their sensitivity for 16 months (the term of observation). PMID- 3087118 TI - [Immunoprophylaxis and immunotherapy of experimental Pseudomonas aeruginosa sepsis]. AB - The protective activity of pyoimmunogen II, lot 9, was studied on P. aeruginosa experimental sepsis used as a model. In experiments on rats the preparation was shown to be nontoxic according to the results of the determination of acute and chronic toxicity. The preparation under test produced a high protective effect in experiments on animals infected with various P. aeruginosa strains, irrespective of their virulence and immunotype. Anti-P. aeruginosa plasma, obtained by plasmapheresis from donors immunized with pyoimmunogen II, showed a curative effect when injected into experimental animals in a dose of 0.02 ml/g body weight at early stages of the infection. PMID- 3087119 TI - [Microbial associations in chronic respiratory tract diseases]. AB - In the peripheral blood of patients with chronic bronchitis the presence of Mycobacterium pneumoniae antigens has been registered in 20.0% of cases and the presence of group A Streptococcus haemolyticus antigens, in 24.0% of cases, the transformation of streptococci into the L-form being observed in 12.0% of cases. The presence of M. pneumoniae, streptococci and their L-forms, as well as associations of these microorganisms, is characteristic of patients with chronic obstructive bronchitis, which is, probably, one of the reasons for the maintenance of bronchial obstruction. In patients with chronic pneumonia and fibrosing alveolitis the antigens of the bacterial form of streptococcus and its L-forms have been detected only in a few cases. PMID- 3087121 TI - [Modelling of an association of Chlamydia trachomatis and Neisseria gonorrhoeae in in ovo experiments]. AB - In experiments in ovo mixed chlamydial and gonococcal infection has been obtained by the successive infection of developing chick embryos with C. trachomatis and N. gonorrhoeae into the yolk sack. The competitive interrelations between the associated microorganisms with respect to their pathogenicity characteristics for chick embryos have not been established. This simulator is intended for use in the primary selection of etiotropic chemical preparations capable of producing combined effect on C. trachomatis and N. gonorrhoeae. PMID- 3087120 TI - [In vitro amino acid requirements of Bacillus anthracis cells]. AB - In the process of batch cultivation in a synthetic medium B. anthracis cells actively consume free amino acids. The maximum amino acid consumption per unit of biomass occurs at the exponential phase of growth, but the consumption of serine is maintained at a high level also during the stationary phase. At the same time the consumption of proline by both vaccine and virulent strains is insignificant at the stationary phase of growth. In contrast to B. anthracis virulent strains, vaccine strains have been shown to consume no lysine, histidine, arginine and tryptophan. PMID- 3087124 TI - Glucoamylase of Aspergillus niger. AB - Aspergillus niger produces two extracellular glucoamylases (GAI of Mr 85 300 and GAII of Mr 77 600) separable on DEAE-cellulose. The enzymes differes in electrophoretic mobility, thermostability and substrate specificity. The GAI/GAII ratio depends on the concentration and form of nitrogen (nitrate or ammonium) in the culture medium. Proteinase VIII from Bacillus subtilis converts GAI to a form showing properties similar to those of GAII. Possible proteolytic degradation of GAI to GAII by Asp. niger endogenous proteinase(s) is suggested. PMID- 3087122 TI - [Delayed hypersensitivity and nonspecific cellular immunity. The cytotoxic activity of macrophages, natural and antibody-dependent killer cells]. AB - The experiment on (BALB/cXC57BL)F1 mice, showing a high level of delayed hypersensitivity (DH) when sensitized with BCG vaccine and Staphylococcus aureus strain B-243, has demonstrated the influence of such sensitization and DH reaction induced by the injection of a specific antigen (old tuberculin or staphylococcal phagolysate) into the sensitized animals on the cytotoxicity of macrophages, natural killers (NK) and antibody-dependent killers (ADK). Sensitization with BCG vaccine alone results in an insignificant rise in the activity of these effector cells, and sensitization with S. aureus produces no changes at all. The pronounced activation of the cytotoxicity of macrophages, NK and, to a lesser extent, ADK has been observed in DH reaction induced by the injection of a specific antigen into the sensitized mice. In the course of DH reaction a rise in the activity of NK and ADK not only against tumor target cells, but also against microbial ones (Candida albicans and S. aureus) has been found to occur. PMID- 3087123 TI - [Preventive properties of the blood sera from persons vaccinated with a Proteus vaccine made from soluble antigen complexes]. AB - In experiments of the passive protection of mice the protective properties of sera obtained from humans before and after their immunization with Proteus vaccine used as a monopreparation or in combination with staphylococcal toxoid and/or pyoimmunogen were studied. When introduced in a single subcutaneous injection, Proteus vaccine prepared from soluble antigenic complexes ensured an increase in the protective properties of sera. The second injection of the vaccine essentially enhanced the protective potency of the sera of the immunized donors. The therapeutic injection of Proteus vaccine ensured the essential increase of the protective properties of the sera. This increase could be experimentally detected within at least 25-30 days from the beginning of immunization. The immunization of volunteers with Proteus vaccine in combination with pyoimmunogen and adsorbed staphylococcal toxoid ensured the maximum increase of the protective properties of their sera. PMID- 3087126 TI - [Diagnosis of the biocomposition of bone tissue using an ultrasonic transmission method]. PMID- 3087125 TI - Blood gas and hemodynamic changes induced by the treatment of pulmonary congestion with vasodilators in the acute phase of myocardial infarction. AB - The effects of vasodilators on hemodynamics and blood gases was assessed in 31 patients suffering from acute myocardial infarction (AMI) who had clinical signs of left ventricular failure with high pulmonary wedge pressure (PWP greater than 15 mm Hg). Molsidomine (n = 10), phentolamine (n = 12) and sulmazol (n = 9) were administered intravenously to decrease the PWP by 20%. Molsidomine significantly decreased PWP after one hour with a mild increase in cardiac index (CI) inducing a slight decrease in paO2 (64 to 59 mm Hg, P less than 0.1) with no change in p vO2. Phentolamine and Sulmazol significantly increased the CI and decreased the PWP, with a substantial increase in the pv-O2 (28 to 32 mm Hg, P less than 0.005 and 28 to 31 mm Hg, P less than 0.001) and no significant change in the paO2 (60 to 65 mm Hg, P less than 0.1 and 68 to 69 mm Hg, NS). None of these drugs significantly changes the pulmonary vascular resistance (PVR) which would explain the lack of any significant change in paO2. The treatment of pulmonary congestion in AMI by either pure venous (molsidomine) or arteriolar and venous (phentolamine and sulmazol) vasodilators does not worsen obviously pre-existant hypoxemia. PMID- 3087128 TI - Skeletal muscle function and energy metabolites in malnourished surgical patients. AB - Skeletal muscle function may be used to assess nutritional status. To approach this hypothesis nine malnourished surgical patients were studied at admission and after two weeks of preoperative total parenteral nutrition. The muscle function variables, force at 10 Hz stimulation (F10), relaxation rate (RR) and endurance (E) were determined. Energy metabolites were measured in muscle biopsies. At admission muscle function and content of energy-rich phosphates were normal, muscle glycogen was low and water was increased. After nutritional therapy, F10 and E were unchanged, RR was increased (p less than 0.05), glycogen was normalized, muscle water remained high while the nutritional markers prealbumin and skin test were markedly improved. In conclusion, skeletal muscle function and content of energy-rich phosphates were normal in semistarved malnourished patients. After nutritional therapy, RR was increased and this may prove useful in following the effect of nutritional repletion. PMID- 3087127 TI - [Ossification in the Achilles tendon]. PMID- 3087129 TI - Continuous subcutaneous insulin infusion: a long-term study. AB - The authors report data obtained from a 3-year study of CSII and humanized insulin (semi-synthetic human insulin) administered to 18 insulin-dependent subjects in the outpatient clinic. The aim of this study was to evaluate the validity of insulin pumps in long-term treatment. Metabolic parameters were significantly improved (p less than 0.001) in the first month and remained so with only slight alterations throughout treatment. The authors underline some metabolic problems (ketosis) caused by malfunctioning of the insulin pumps, by the difficulties with the infusion system or by nodular skin lesions at the infusion site. Only these lesions called for treatment to be discontinued in 4 patients. The highest incidence of nodular skin lesions was seen after one year's uninterrupted treatment and they seem connected to the duration of treatment rather than to the patients' negligence (inadequate hygiene, delayed needle substitution). The authors conclude that CSII treatment is valid over short-term periods, whereas it presents drawbacks over long-term administration. PMID- 3087130 TI - Comparison between pituitary computed tomographic findings and tests of hypothalamo-pituitary function in 72 patients with hyperprolactinaemia. AB - To verify the diagnostic capacity of some dynamic tests of the prolactin (Prl) secretion, the findings obtained by high-resolution computed tomography (CT) were compared with results obtained from tests using nomifensine (NOM) domperidone (DOM) and thyrotrophin-releasing hormone (TRH) in 72 patients with pathological hyperprolactinaemia. None of the patients with tumours had a positive Prl response to NOM or to DOM administration; however, a positive response to these tests was present in only 24 and 41%, respectively, of the patients with normal CT picture. The results of TRH testing were similar to those obtained with DOM. Different neuroendocrine patterns were disclosed by comparing pituitary Prl and thyrotrophin (TSH) responses to DOM: 1) some subjects had a reduced Prl response together with an exaggerated or normal TSH response to DOM; they comprised patients with tumour, empty sella, and normal CT picture; 2) other patients with normal CT picture had a positive Prl and a normal TSH response to DOM. These results demonstrate that a negative Prl response to NOM and DOM characterizes all patients with adenoma; however, the tumour-like responses in patients with no visible tumours seem to reduce the diagnostic value of these tests, unless the latter may predate the radiological appearance of an adenoma. On the other hand, a positive Prl and a normal TSH response to DOM exclude the presence of a pituitary tumour. This diagnostic finding is strengthened by the positive response also to NOM. Whatever may be the diagnostic validity of dynamic tests, they provide sound information on the functional state of dopamine neurotransmission. PMID- 3087131 TI - Characterization of the pituitary response in the TRH test by kinetic modeling. AB - Applying the principles of chemical kinetics to the time course of TSH concentrations after TRH infusion, individual values for total TSH release from the pituitary, TSH elimination and release rates, and latency for TSH release were found for 40 patients. Justification for using the observed peak TSH elevation as a consistent reflection of the total TSH release was provided by the high correlation between these two (r = 0.97, P less than 0.001). Kinetic modeling indicated that the most consistent reflection of total pituitary TSH response is the TSH elevation over baseline 35 min after TRH (with the peak expected 30 min post-TRH), rather than the area under the curve. PMID- 3087132 TI - Combined FSH and LH secreting pituitary adenoma in a young fertile woman without primary gonadal failure. AB - A 28 year old fertile woman presented with a history of amenorrhoea and galactorrhoea, and an enlarged pituitary fossa. Serum FSH and LH were repeatedly elevated both basally (32 and 44 mIU/ml) and after LRH (peak values, 108 and 420 mIU/ml). One mg of oestradiol (E2) benzoate im daily for 5 days failed to lower basal or LRH-stimulated serum gonadotrophins. Serum E2 was 170 pg/ml, basal serum prolactin (Prl) was 30 ng/ml and responded briskly to TRH (peak value 103 ng/ml). An 0.8 X 0.8 cm tumour was selectively excised by transsphenoidal surgery. Menses reappeared soon afterwards accompanied by normalization of serum FSH and LH plus biochemical evidence of ovulation. Specific immunostaining of tumoural cells was achieved with either FSH or LH antiserum, and adequate suppression of staining was obtained after preabsorbing each antiserum with and excess of its respective antigen. Our patient appears to be the first documented female with a combined FSH and LH producing pituitary tumour and no prior evidence of primary gonadal failure. PMID- 3087133 TI - Postnatal development of brain TRH, serum TSH and thyroid hormones in the male and female rat. AB - The postnatal development of immunoreactive TRH in the central nervous system (CNS), serum TSH and thyroid hormones was studied in both male and female normal rats. While in most structures of the CNS, TRH increased until day 20-30, serum TSH values peaked at day 15 as did T4. Significant differences were also obtained between both sexes in these parameters. These data further support the fact that pituitary-thyroid axis maturation is independent of brain TRH. PMID- 3087134 TI - The effect of oestriol and tamoxifen on oestradiol induced prolactin secretion in anaesthetised rats. AB - In ovariectomized rats oestradiol and oestriol administered sc for 5 days increased basal plasma prolactin in a dose related manner to similar maximal values. The data fitted log dose-response curves. Oestradiol was about 12 times more potent than oestriol. These dose response relationships were retained on thyrotrophin releasing hormone (TRH) administration (50 ng iv, blood sampled 5 min post TRH). In addition, significantly higher maximal response values for both oestradiol and oestriol were now seen. The relative potency also increased in oestradiols favour. We subsequently examined the effect of co-administering oestriol with oestradiol on plasma secretory responses to a single dose of oestradiol in young male rats: Oestriol (30 micrograms) potentiated increases in basal plasma prolactin, TRH stimulated prolactin secretion and radioimmunoassayable pituitary prolactin in rats in response to a single sc injection of oestradiol (10 micrograms). Tamoxifen, administered once also potentiated these responses to a single sc injection of oestradiol. However, if the tamoxifen was administered sequentially i.e. 48 and 24 h before or 48 and 24 h before and simultaneous with the oestradiol the potentiation was completely reversed. PMID- 3087135 TI - Malignant "triton" tumor with metastatic hemangiopericytoma in a patient associated with von Recklinghausen's disease. AB - An autopsy case of malignant schwannoma in a 31-year-old female associated with von Recklinghausen's disease with unusual elements is reported. The patient who was diagnosed as von Recklinghausen's disease from a biopsy specimen of a subcutaneous tumor in her shoulder and multiple cafe au lait spots in her chest and back, complained of gradual increase in pain in her lower abdomen. A large mass measuring about 18 cm in diameter was located in her left retroperitoneum. Malignant schwannoma associated with von Recklinghausen's disease was indicated by the cellularity of the tumor, intersecting bundles of spindle cells, alternating cellular and less cellular myxoid areas in the peripheral portion of the tumor, whereas a large part of the tumor had a hemangiopericytoma-like arrangement with gaping blood vessels. In addition, however, foci of rhabdomyosarcomatous differentiation and of angiosarcomatous components were found in some areas of this tumor. Moreover, intravascular schwannian growth, which was presumably related to von Recklinghausen's disease, was observed in the heart and thyroid. This tumor should be classified as a malignant triton tumor because of the presence of rhabdomyoblasts. PMID- 3087137 TI - O-dealkylation of phenacetin in the olfactory rosette in rainbow trout (Salmo gairdneri). AB - Olfactory rosettes from trout (Salmo gairdneri) were found to metabolise (14C ethyl)-phenacetin to 14CO2 in vitro. Based on wet weight, the rate of metabolism was lower than that in liver and gills. Based on protein content, the rate of metabolism was about equal to that in liver and gills. Addition of the cytochrome P-450 inhibitors metyrapone, 9-hydroxyellipticine and piperonyl butoxide significantly decreased the formation of 14CO2 from (14C-ethyl)-phenacetin in olfactory rosettes. Microautoradiography of rosettes incubated with (14C-ethyl) phenacetin showed the presence of non-extractable metabolites in the sensory and indifferent epithelium. Addition of metyrapone decreased the binding of radioactivity in the epithelia considerably. When olfactory rosettes were incubated with (14C-dimethylamine)-aminopyrine, no formation of 14CO2 was observed. The results are concluded to indicate that cytochrome P-450 dependent enzyme activity is present in the epithelia of the trout olfactory rosette. PMID- 3087136 TI - Rubidium uptake by mouse pancreatic islets exposed to 6-hydroxydopamine, ninhydrin, or other generators of hydroxyl radicals. AB - The purpose was to study the toxicity of drugs known to generate free radicals on isolated pancreatic islets. The accumulation of 86Rb+ by mouse pancreatic islets was measured in vitro. Exposing the islets to 6-hydroxydopamine, ninhydrin, or phenazine methosulphate+NADH inhibited the Rb+ uptake, whereas paraquat or acetylphenylhydrazine had no effect. This effect of 6-hydroxydopamine was prevented by either of the hydroxyl radical scavengers, sodium benzoate and mannitol, but not by the non-scavenger, urea; ninhydrin was partially protected against by mannitol but not by benzoate. Protection against 6-hydroxydopamine was also afforded by D-glucose but not by L-glucose or 3-O-methyl-D-glucose; none of the sugars protected against ninhydrin. In damaging islet beta-cells and in being protected against by D-glucose, 6-hydroxydopamine closely resembles the diabetogenic drug, alloxan. It is suggested that protection against alloxan may involve both glucose metabolism and the interaction of glucose with its membrane located carrier, while protection against 6-hydroxydopamine appears to be unrelated to the hexose carrier mechanism. PMID- 3087138 TI - The phorbol ester TPA induces hormone release and electrical activity in clonal rat pituitary cells. AB - The phorbol ester TPA activates the protein kinase C in a similar way as 1,2 diacylglycerol. The effect of TPA on prolactin (PRL) secretion and electrical properties of rat pituitary cells in culture (GH4C1 cells) were compared with the effects of thyroliberin (TRH) on the corresponding parameters. The rate of hormone release was measured using a parafusion system optimized to give high time resolution. Samples for PRL measurements were taken every 4 s. The TRH evoked a biphasic PRL release, with a transient peak after about 30 s followed by a lower but sustained enhancement of the secretion. The TPA mimicked the late phase of the secretory response to TRH. The TPA analogue, 4 alpha-PDD, had no effect on the PRL release. The TRH also evoked biphasic membrane potential changes in the GH4C1 cells; the late phase consisting of membrane depolarisation associated with increased input resistance and enhanced firing of Ca2+ dependent action potentials. The TPA mimicked to a great extent these late phase effects of TRH, whereas the inactive analogue 4 alpha-PDD was ineffective. Continuous exposure to TPA masked the late phase of the electrophysiological response to TRH, suggesting that TPA and TRH share common mechanisms in their action on GH4C1 cells. We suggest that TRH enhances the electrical activity in these cells due to protein phosphorylation induced by diacylglycerol activation of protein kinase C, which in turn suppresses the membrane permeability to K+. PMID- 3087139 TI - Apparatus and methodology for microcarrier cell culture. PMID- 3087140 TI - Clinical chemistry of folic acid. PMID- 3087141 TI - Enzymology and physiology of reticulocyte lipoxygenase: comparison with other lipoxygenases. PMID- 3087142 TI - The stereochemistry of the reactions of lipoxygenases and their metabolites. Proposed nomenclature of lipoxygenases and related enzymes. PMID- 3087143 TI - Androgen receptors in normal and abnormal male sexual differentiation. PMID- 3087144 TI - Progesterone resistance. PMID- 3087145 TI - Suggested nomenclature for aesthetic and reconstructive surgery of the breast. Part III: Gynecomastia. PMID- 3087146 TI - [Extraocular (transscleral) retinal photocoagulation with a CO2 laser beam]. PMID- 3087147 TI - [Gangliosides of the human and monkey lens]. PMID- 3087148 TI - [Endophotocoagulation using the carbonic dioxide laser]. PMID- 3087149 TI - The decision to forego life sustaining treatment. PMID- 3087150 TI - The effects of DRGs on the pattern of admission of medicare patients. PMID- 3087151 TI - Softball injuries: cost, cause and prevention. PMID- 3087152 TI - Changing perspectives in the prevention of coronary artery disease. AB - Today the question is no longer whether cholesterol reduction is beneficial for those at risk for coronary artery disease; the questions now are when, whom and how to treat. Areas of great interest include extrapolation of current trial results to low density lipoprotein reduction by diet and drugs, and assessment of the value of increasing high density lipoprotein levels by pharmacologic means. We will need to decide what measurements (total cholesterol, lipoprotein cholesterol or lipoprotein apoprotein levels) are of most value to the diagnosis, treatment and follow-up of the at-risk patient. Recommendations, including those of the recently published National Institutes of Health Consensus Panel on Cholesterol Lowering, suggest that our index for diagnosis and treatment should be set considerably lower than it is today. To be successful with a more aggressive approach to cholesterol lowering, we will need to better support, educate and motivate the at-risk patient. Physicians need to become more knowledgeable about what plasma cholesterol is and how to change it. Methods that enhance patient adherence to diet and drug therapy must be developed. We will need to alter lifetime habits and will need the help of both the food industry and better informed consumers, knowledgeable on how to read food labels, if we are to succeed. Ultimately, we will need a 2-pronged approach, focusing on both the physician and the public at large. PMID- 3087153 TI - Potentiation of the thermic effect of insulin by exercise: differences between lean, obese, and noninsulin-dependent diabetic men. AB - We studied the effects of prior high-intensity cycle exercise (85% VO2 max) on total energy expenditure (EE) and the thermic effect of insulin (TEI) in normal controls and in obese insulin-resistant and noninsulin-dependent diabetic (NIDDM) subjects. Normal controls, but not obese or NIDDM subjects, showed a significant increase (3-7%) in total EE 12-16 h after exercise (p less than 0.05). Prior exercise increased lipid and decreased glucose oxidation in all groups. During low-dose insulin infusion (40 mU X M2 X min), prior exercise potentiated TEI in control and NIDDM subjects (p less than 0.05), whereas obese subjects showed no response. During high-dose insulin infusion (400 mU X M2 X min), TEI was similar in NIDDM and control subjects but was significantly less in the obese group. In this study, we found a positive correlation between TEI and insulin-stimulated rates of glucose disposal (r = 0.91, p less than 0.001). The predicted cost of glucose storage accounted for 42% of TEI. PMID- 3087154 TI - Superior sulcus tumors. AB - A retrospective analysis of 35 patients treated for superior sulcus tumors of the lung at UCLA was performed for the years 1960-1983. Follow-up ranged from 19 months to 21 years, with all but one patient followed at least 2 years. The 28 patients with localized disease were treated by megavoltage irradiation with or without surgical resection and had a 5-year survival (product-limit) of 21%. However, the 15 patients receiving combined treatment had a 48% 5-year survival (p = 0.009). An effort was made to identify those factors affecting survival. Patients presenting with no radiographic evidence of nodal enlargement appeared to have a survival advantage with a survival of 31% at 3 years, versus no survivors among those with positive nodes (p = 0.059). Bony erosion contiguous with the primary tumor at presentation was found not to affect the prognosis. Patients with local control of the primary tumor showed a survival of 71% vs 0% for those locally recurring. Those patients receiving at least 55 Gy showed a trend toward increased survival though not with statistical significance. The pattern of failure was evaluable in 25 patients. Local recurrence was observed in 18 patients (72%) with seven (39%) of these manifesting as spinal cord compressions. Distant metastases were seen in 35% of recurrences, and as the sole site of disease in only 10%. Three patients developed brain metastases, all of whom had concomitant local failure. Significant pain relief was achieved in 74% of patients. However, it was transient in 60% of these. We conclude that superior sulcus tumors remain primarily a localized problem, and that aggressive treatment is indicated even with apparently local invasive disease. PMID- 3087155 TI - The challenge of prospective reimbursement for oncology practice. PMID- 3087156 TI - Overgown use for infection control in nurseries and neonatal intensive care units. AB - We surveyed 1824 physicians to determine current newborn nursery (NBN) and neonatal intensive care unit (NICU) gowning procedures and the gowning preferences of NBN and NICU physicians. A total of 712 questionnaires (39.0%) were returned from 453 hospitals. Of the 712 questionnaire respondents, 251 (35.3%) thought that gowns should be worn at all times. However, 319 (72.8%) of the 438 NBNs and 317 (71.6%) of the 443 NICUs surveyed continue to require gowns at all times. The difference between gown preference and practice was statistically significant. Gowns were worn only for handling infants in 96 NBNs (21.9%) and 109 NICUs (24.6%), while 344 physicians (48.3%) preferred this regimen. Gowns were worn in 16 NBNs (3.7%) and 15 NICUs (3.4%) only for isolated infants, but 67 respondents (9.4%) believed this to be the procedure of choice. At our institution, 100 and 300 gowns are worn daily in the NBN and NICU, respectively, at a cost of +0.28 per gown use, generating an estimated yearly expense of +40 880. In addition, the current literature does not support gowning as a means of infection control in this setting. PMID- 3087157 TI - Gastroesophageal reflux secondary to gastrostomy tube placement. AB - We evaluated five children with severe psychomotor retardation who developed frequent vomiting and poor weight gain after surgical placement of a feeding gastrostomy tube. Prolonged pH probe testing before surgery did not reveal notable gastroesophageal reflux (GER). Treatment with 12-hour gastrostomy tube feeding resulted in a marked reduction in vomiting; after one year of continuous feeding, all patients had achieved significant weight gain (mean, 44.0%). Esophageal manometrics and 24-hour pH probe testing before and at the end of the 12-month continuous-feeding period demonstrated low pressures of the lower esophageal sphincter and significant GER in the five children studied. These results indicate that children may develop symptomatic GER after gastrostomy tube placement. In such patients continuous gastrostomy tube feeding may result in a cessation of vomiting and achievement of significant weight gain. Definitive antireflux surgery can then be performed with the patient in an improved nutritional state. PMID- 3087158 TI - Effect of IgG anti-Rho(D) in adult patients with chronic autoimmune thrombocytopenia. AB - Seventeen adult patients with chronic (15 cases) or acute (two cases) autoimmune thrombocytopenia (ITP) were given intravenous and/or intramuscular injections of 0.75-4.5 mg of IgG anti-Rho(D) over a period of 1-5 days. Significant elevations of the platelet count (increments greater than 50 X 10(9)/liter) resulted in 13 of 15 Rh-positive patients but not in either of two Rh-negative patients. Heat aggregated human albumin given to one of the Rh-negative patients also did not lead to a significant increase of the platelet count. The elevation of the platelet counts in Rh-positive patients after IgG anti-Rho(D) administration was often transient (less than 4 weeks), but long-term benefit (greater than 5 months) was achieved in five cases. The IgG concentration on RBC from five Rh positive patients studied increased from a usually undetectable value before to approximately 700-1,700 IgG molecules/per RBC after anti-Rho(D) administration resulting in a strongly positive direct antiglobulin test. Nevertheless, an overt clinical hemolysis was seen in only one patient. The clearance of autologous 51Cr labeled RBC was determined in four patients and was slightly enhanced in three and normal in one splenectomized patient. We conclude that the Fc receptor blockade involved in platelet sequestration was not associated with the induction of significant RBC clearance and that a reversible interaction of sensitized RBC with phagocytic cells and/or a low-grade destruction of these cells might be sufficient for the elevation of circulating platelets in the majority of patients with ITP. PMID- 3087159 TI - Investigation of a case of subtype IIC von Willebrand disease: characterization of the variability of this subtype. AB - A variant of von Willebrand disease (vWD) has been identified in a 19-year-old woman with a severe bleeding syndrome. She had a very prolonged bleeding time (over 20 min), 24 U/dl factor VIII coagulant activity (F.VIII:C), 16 U/dl von Willebrand factor antigen (vWF:Ag), no ristocetin cofactor activity, and an anodal mobility of vWF:Ag on crossed immunoelectrophoresis (CIE). vWF:Ag was markedly reduced in her platelet lysate. In plasma and platelets, SDS-agarose electrophoresis consistently demonstrated the absence of large multimers, a relatively increased concentration of the fastest-moving multimer, and gross abnormalities of the internal structure of each vWF multimeric unit. Five members from the maternal side of the family had a double vWF:Ag peak by CIE and a relative increase of the fastest-moving vWF multimer by SDS-agarose electrophoresis; no quantitative or qualitative vWF defects were found in the paternal side of the family. The pattern of the findings in the propositus and her family is similar to those of type IIC vWD. However, there are some unique characteristics suggesting phenotypic variability in this subtype, such as low level of platelet vWF:Ag and the absence of increase of vWF after DDAVP administration. PMID- 3087160 TI - Significance of the lupus anticoagulant. PMID- 3087161 TI - The significance of hyperpipecolatemia in Zellweger syndrome. AB - The plasma pipecolic acid concentration in two newborn infants with Zellweger syndrome at ages 4 and 10 days were 7.8 and 7.7 microM. Reported concentrations from this laboratory for normal newborn infants averaged 12 microM +/- 5.6 (SD). Both patients had the facies and severe hypotonia characteristic of the disease. Autopsy examination at age 6 days in one of these patients revealed the developmental microscopic abnormalities in brain, liver, and kidney that are associated with Zellweger syndrome. In three additional patients ages 3 1/2 weeks, 2 months, and 2 months, the pipecolic acid concentrations were 15, 17, and 25 microM. The concentrations increased to distinctly pathological levels on subsequent assays at a later age. It is concluded that the hyperpipecolatemia in Zellweger syndrome occurs postpartum and that the plasma concentrations may not be diagnostic early in life. The major manifestations of the disease, already evident at birth, cannot be attributed to pipecolatemia. Currently available data do not exclude the possibility of pipecolic acid accumulation in the brain where it has been reported to be a major metabolite of lysine. Hyperpipecolatemia of considerable degree is also consistently found in familial hyperlysinemia where it appears to be benign. PMID- 3087162 TI - Cost-benefit analysis of an aminoglycoside monitoring service. AB - The clinical and financial impact of an aminoglycoside monitoring service was determined. All patients admitted to a 74-bed general medicine unit and treated with tobramycin or gentamicin during a six-month study period were eligible for the study. The first three months served as a control period during which pharmacists used published audit criteria and modifications of those criteria to monitor the appropriateness of gentamicin and tobramycin use in patients but did not attempt to intervene in aminoglycoside prescribing. During the next three months, pharmacists provided physicians with recommendations for choice of drug, coordinated blood sampling times, and designed individualized dosage regimens for all patients treated with gentamicin or tobramycin. Data for financial analysis were obtained from pharmacy profiles and medical records, and the cost:benefit ratio for the service was calculated. A total of 118 patients were included in the study. Significant improvements in appropriateness of tobramycin therapy, adequacy of loading dose, frequency of monitoring for ototoxicity, and serum concentration monitoring were noted in the intervention group. Despite an increase in gentamicin use from 20% in the control group to 61% in the intervention group, the incidence of aminoglycoside toxicity did not increase significantly. The cost:benefit ratio was 1.13, which indicates that the service is an appropriate use of resources. The aminoglycoside monitoring service had a favorable impact on the use and cost of aminoglycoside antibiotics. Expansion of the service to all areas of the hospital served by satellite pharmacies could reduce drug expenditures by as much as $55,000 per year. PMID- 3087163 TI - Cost-effectiveness of routine radiochemical quality assurance testing of technetium Tc 99m radiopharmaceuticals. AB - The cost-effectiveness of performing routine radiochemical quality assurance (QA) testing of technetium Tc 99m radiopharmaceuticals was evaluated. Data were collected retrospectively on use and failures of radiopharmaceuticals over a 30 month period at a university hospital. Cost of quality assurance testing of the radiopharmaceuticals and cost of not performing this routine testing (e.g., repetition of invalid studies) were compared. Possible reasons for failure of radiopharmaceuticals to meet QA standards were examined. Based on these data and an informal survey of the incidence of failures at other nuclear pharmacies, expected radiopharmaceutical failure rates were calculated. The incidence of failures at the study institution was 0.56% (20 of 3775); the other nuclear pharmacies reported similar data. Based on these data, 6 failures per 1000 technetium Tc 99m radiopharmaceuticals prepared were predicted. "Low tin" kits (e.g., albumin aggregated) with low-specific-activity sodium pertechnetate Tc 99m were associated with failure to meet QA standards. Direct costs of QA testing were slightly less than direct costs associated with not testing; however, consideration of indirect costs confirmed the cost-effectiveness of QA testing. Routine radiochemical QA testing of technetium Tc 99m radiopharmaceuticals appears to be cost-effective. PMID- 3087164 TI - Personnel costs and preparation time in a centralized intravenous admixture program. AB - The amount of time and the cost of personnel time associated with the preparation of injectable products were determined. A time study consisting of 9041 observations during a seven-day period was conducted to determine the amount of time required of pharmacists and technicians for the preparation of total parenteral nutrient (TPN) solutions, large-volume injectables, antibiotic admixtures, antineoplastic admixtures, and investigational drugs. The established times were used to calculate relative value units for each product line and to determine the cost of pharmacist and technician time associated with the preparation of each product line. Preparation times ranged from 3.7 minutes for an antibiotic admixture to 49 minutes for a pediatric TPN solution. Total personnel costs ranged from $0.71 for an antibiotic admixture to $10.70 for a pediatric TPN solution. The calculated relative value units indicated that existing departmental time standards did not allow sufficient time for the preparation of some products. Establishing relative value units and calculating the cost of personnel time associated with the preparation of injectable products can be helpful for comparing the cost of purchasing ready-to-use products with the cost of preparing the same products. PMID- 3087165 TI - Stability of Liposyn II fat emulsion in total nutrient admixtures. AB - Compatibility and safety of a safflower oil-soybean oil lipid emulsion (Liposyn II, Abbott) with amino acids and dextrose in total nutrient admixtures (TNAs) were studied. Sixty-two admixtures representing 31 different combinations of fat emulsion, amino acid injection, and dextrose injection were tested. Both 10% and 20% concentrations of the fat emulsion and three concentrations each of amino acid injection and dextrose injection were used; the core admixture components were placed in empty flexible plastic bags in three different sequences: fat, amino acids, dextrose; fat, then dextrose and amino acids simultaneously; and amino acids and dextrose simultaneously, then fat. One of two mixtures of electrolytes and trace metals was added to each sample at the end of mixing. Six samples were tested after one day at 25 degrees C, 35 after two days at 5 degrees C plus one day at 30 degrees C, and 21 after nine days at 5 degrees C plus one day at 25 degrees C. Multivitamin injections were added to each TNA just before the 24-hour room-temperature storage. pH, emulsion particle size, and zeta potential (electrostatic surface charge of lipid particles) were measured after visual inspection of each sample. Amino acids were separated by high-performance liquid chromatography and measured. Dextrose was measured by size-exclusion chromatography. In a controlled study of 24 dogs, six-hour infusions of TNAs containing Liposyn II 20% were administered for 14 days, after which all major organs and tissues were studied microscopically. At all storage times in the compatibility study, all TNAs retained a uniform, milk-like appearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087166 TI - Immunocompromised animal models for the study of antibiotic combinations. AB - Studies of various models of Pseudomonas aeruginosa infections in neutropenic animals have demonstrated the superiority of the combination of beta-lactam and aminoglycoside antibiotics when compared with a single drug alone. A limited number of studies carried out in models of Klebsiella pneumoniae infections in neutropenic animals have shown similar results. The efficacy of double beta lactam combinations for the treatment of gram-negative bacillary infections has not been studied as extensively; the few available reports did not show any benefit over a single beta-lactam treatment. Most studies of combined therapy in gram-positive infections have been performed in the experimental endocarditis model. Experiments in Staphylococcus aureus, Streptococcus viridans, and Streptococcus faecalis endocarditis have shown a clear-cut advantage for combined beta-lactam/aminoglycoside treatment over single beta-lactam therapy, as predicted by in vitro tests. The enhanced efficacy of combined beta lactam/aminoglycoside treatment in both gram-negative bacillary and gram-positive coccal infections appears to result in most studies in increased and faster killing of the bacteria. With P. aeruginosa infections, however, experiments in neutropenic mice suggest that in addition to increased killing, the beta-lactam arm of the combined treatment prevents the emergence of the small colony variants that lead to treatment failures during therapy with aminoglycoside alone. For both gram-negative bacillary and gram-positive coccal infections, in vitro tests that demonstrated synergism for the combined antibiotics generally predicted enhanced therapeutic efficacy in vivo. Conversely, when no synergism was demonstrated in vitro, there was generally no increased efficacy of combined treatment in vivo. Animal models add a dimension to our understanding of the efficacy of antibiotics, both singly and in combination, that is not always apparent from the results of in vitro tests alone. These in vivo tests can be of value when planning clinical trials. PMID- 3087168 TI - Cyclopia as a result of an unbalanced familial translocation, rcp(7;18)(q34;q21) AB - One fetus is described with cyclopia and associated abnormalities as a result of an unbalanced translocation involving chromosomes 7 and 18 [46XX,del 7, rcp(7;18)(q34;21)]. The parents had had a previous infant described as having possible holoprosencephaly, but no medical records were available to substantiate this description. PMID- 3087167 TI - Learning effect of repeated hypercapneic ventilatory response testing. AB - To determine whether hypercapneic ventilatory response (HCVR) is affected by repeated testing, the HCVR of 22 healthy subjects was determined daily for 4 consecutive days. The slope (S) of the HCVR increased to a maximum on Day 3, which was 14% greater than S on Day 1 (p less than 0.05). The increase in airway occlusion pressure during progressive hypercapnea (delta P0.1/delta PCO2) showed no significant change, indicating that although S and delta P0.1/delta PCO2 are both good measurements of ventilatory response, they are not totally interchangeable in normal subjects. A subgroup of 12 subjects (termed "increasers") was responsible for the overall increase in S. For this subgroup, S was significantly smaller on Day 1 than on each subsequent day. Increasers also had a significantly greater value of S on each day of the study than subjects who did not increase ("decreasers"). On Day 1, increasers' S was 3.77 +/- 1.31 L min 1 mm Hg-1, while decreasers' S was 2.46 +/- 1.00 (p less than 0.001). Some normal subjects demonstrate a learning effect during repeated daily testing of HCVR by the rebreathing technique, and those subjects whose S increases are those with large initial values of S. PMID- 3087169 TI - Fetal valproate syndrome. PMID- 3087170 TI - The Rett syndrome. PMID- 3087171 TI - Clinical recognition of Rett syndrome. AB - Key manifestations helpful in diagnosing Rett syndrome include progressive loss of previously acquired psychomotor skills, apraxia with loss of use of hands and legs, and "handwashing" automatisms. Four types of clinical presentation can be described: a neurodegenerative disorder, an autistic syndrome, a Lennox-Gastaut syndrome, and a chronic encephalopathy. Carbamazepine currently appears to be the anticonvulsant of choice. The mild lactic and pyruvic acidosis along with the ultrastructural abnormalities of mitochondria in brain and liver biopsies point to a generalized disorder of energy metabolism. PMID- 3087172 TI - Physical growth and development in patients with Rett syndrome. AB - Linear growth and sexual development was assessed in 21 girls who fulfilled the clinical criteria of Rett syndrome. Ten (48%) showed growth retardation with length or height below the 5th centile and an additional 8 (38%) had shifted their linear growth downward sometime during the first years of life. All the girls had age-appropriate sexual development with menarche in 6 at a mean age of 11 2/12 years. Early deceleration of linear growth, growth retardation and normal sexual development appear to be useful markers in the clinical definition of Rett syndrome. PMID- 3087173 TI - Autism and Rett syndrome: some notes on differential diagnosis. AB - Rett syndrome and infantile autism share the common symptom of autism, especially in the early stages of the disorders. In the later development of Rett syndrome autism sometimes becomes less prominent and there may also be clear differences as regards the quality of autistic behaviour in Rett syndrome and infantile autism. However, in infancy, the syndromes may be indistinguishable. The present paper deals briefly with this issue and suggests that in many girls referred in infancy for autistic symptoms Rett syndrome should be considered seriously as a primary diagnostic alternative. PMID- 3087174 TI - Shift to righthandedness in Rett syndrome around age 7. AB - This paper confirms Nomura's finding (Nomura et al, 1984) that almost all of those children with Rett syndrome under 7 who grasp objects are lefthanded. It is suggested that the lefthandedness in Rett syndrome up to age 7 comes from a functional lateralization of the cerebral hemispheres similar to that which Birkmayer and Rett proposed for normal infants up to age 1 (Birkmayer and Rett, 1954). However, examination of children over 7 showed that almost all of those patients who grasp objects prefer the right hand and show symptoms of disturbance of the functions of the pyramidal tract that are more pronounced in the left than in the right upper limb. It is suggested that in connection with the severe developmental retardation of the CNS in Rett syndrome the right shift factor of handedness (Annett, 1981) has a belated manifestation. Within the framework of a regression of the CNS there occurs a regression which is more pronounced in the right cerebral hemisphere than in the left. PMID- 3087175 TI - Motivational conflicts in Rett syndrome. AB - Some of the peculiar symptoms of Rett syndrome including stereotypic wringing and washing hand movements, staring, social withdrawal, bouts of hyperpnea, are interpreted as the expression of motivational conflicts occurring in severely brain damaged patients unable to perform useful hand movements. These behaviours can be considerably reduced, if external 'requests' are substantially diminished and sources of keen interest (stories, music, face to face interactions) are activated. These preliminary observations were derived from 34 patients seen by the author. PMID- 3087176 TI - Auditory processing deficit in a patient with Rett syndrome. AB - Because of the consistent and prominent language failure in Rett syndrome, a patient with the characteristic phenotype was tested for subtle auditory processing deficits by visual reinforcement audiometry. In spite of excellent detection threshold and frequency discrimination, frequency sweep discrimination was at a chance level. This discrimination is normally performed by 5-8 month old infants. This observation suggests a defect in the specialized units of the inferior colliculus or higher auditory centers which subserve frequency sweep discrimination. PMID- 3087177 TI - Operant studies of self-injurious hand biting in the Rett syndrome. AB - Two children with Rett syndrome were treated for their self-injurious hand biting. Results of an operant assessment showed that in both cases the behavior functioned as a self-stimulatory response. Differential reinforcement, combined with a response interruption technique, produced large reductions in the hand biting of both girls and increases in the motor performance (instruction following, toy play) of one girl. These results suggest that further operant investigations may be helpful in the understanding and management of the behavioral symptoms found in Rett syndrome. PMID- 3087178 TI - Breathing impairment in Rett syndrome. AB - Four patients with Rett syndrome had prominent abnormalities of breathing during active wakefulness, characterized by prolonged apnea intermixed with irregular and frequent respiratory movements. The apneic periods were associated with severe drops in O2 saturation, which assumed a periodic pattern. Respiration was regular during sleep and quiet wakefulness. These respiratory patterns seem characteristic of Rett syndrome and are probably related to impairment of the behavioral control system of respiration. These severe hypoxic episodes could contribute to permanent neurologic damage and secondary neurochemical changes. PMID- 3087179 TI - "Forme fruste" of Rett syndrome--a case report. AB - We report on a 17-year-old girl considered to represent a "forme fruste" of Rett syndrome. The history showed normal psychomotor development until age 20 months, when the girl successively lost acquired speech and developed autistic traits, moderate dementia, partial apraxia and microcephaly. However, she never stopped using her hands purposefully, nor did she develop the hand stereotypies characteristic of Rett syndrome. From age 4 years she successively became more communicable and regained some of the previous abilities including some speech. At 17 she showed most of the abnormalities characteristic of adolescent girls with Rett syndrome but was still only moderately retarded, with remarkably preserved motor functions. She had a peculiar apraxia. She seemed to lack "the key" to using her hands, while retaining a pincer grasp and some manipulative skills in her fingers. - It is suggested that the phenotype of Rett syndrome can vary considerably and that "formes frustes" may not be an exceptional rarity among mentally retarded girls. PMID- 3087180 TI - Atypical forms of Rett syndrome. AB - In the absence of any biological marker, Rett syndrome (RS) is defined by clinical criteria which have been proposed at the second Vienna conference on RS and patients who do not fulfill those criteria cannot be included. However, some patients partially fulfill the criteria but lack some of the essential characteristics. Seven such patients are reported. All patients were girls. Atypical manifestations included absence of a normal development during the first months of life (5 patients), absence of deterioration (1 patient), or presence of initial and intense seizure activity (2 patients). If such cases are indeed atypical RS, the spectrum of clinical manifestations will have to be broadened and deterioration of previously acquired skills may not be an essential requirement for its diagnosis. The exclusive occurrence of atypical and of typical cases in females suggests that both constitute a single morbid entity. PMID- 3087181 TI - Rett syndrome and the electroencephalogram. AB - The EEG is almost always abnormal in patients with Rett syndrome. This is demonstrated in a study based upon 230 EEG records obtained from 44 patients. Rhythmical slowing (mostly 3-5/sec) represents the most common EEG abnormality (30 patients). Diffuse, scattered or bilateral-synchronous spikes or sharp waves were found in 22 patients. Slow spike-wave complexes were present in 9 patients. With advancing age, the EEG abnormalities tend to decline and ill-defined low voltage records may develop. These changes may parallel an intrinsic disease course with an early active phase followed by a phase of residual impairment. PMID- 3087182 TI - Positron emission tomographic study of D2 dopamine receptor binding and CSF biogenic amine metabolites in Rett syndrome. AB - We report on the first positron emission tomographic study of dopamine receptor binding in Rett syndrome. The patient is a 25 year old Austrian woman diagnosed at age 2 and followed since then by Rett. A computed axial tomogram (CT scan) showed cortical atrophy, and enlarged ventricles but normal structure of the caudate/putamen. Following the CT scan 20 mCi of 11 C N-methyl spiperone, a butyrophenone with a high affinity for dopamine D2 receptors was administered intravenously. The patient was found to have dopamine D2 receptor binding activity in the low normal range. The caudate/cerebellar activity ratio was below the mean regression line (p = 0.10) that relates the CA/CB ratio as a function of age. Levels of cerebrospinal fluid neurotransmitter metabolites were normal. PMID- 3087183 TI - Rett syndrome. History and general overview. AB - The syndrome under discussion probably has a much longer history than we know. The first description of 20 years ago noted only the similarities of behavior and neurological, psychological, and social symptoms of the affected patients. The publication by B Hagberg in the US drew world-wide attention to the syndrome. Since the development of the child proceeds unremarkably during the first year of life parents find it particularly difficult to understand and to cope with the subsequent arrest of motor, language and intellectual development. The present lack of a causally effective treatment does not relieve us from the task to do all we can to preserve existing capabilities and functions. Experience tells us that the gaze of the affected children, which seems very intense and is accompanied by hypomimia or amimia, is the focus of any possibility for social contact. Parents often report on their visual contact with the child which should spur greater efforts to work on that phenomenon. PMID- 3087184 TI - Rett syndrome: positron emission tomography (PET) studies. PMID- 3087186 TI - The role of therapy in Rett syndrome. AB - The purpose of Occupational, Physical and Music Therapy in the treatment of girls with Rett syndrome is to maintain and maximize function. Specific approaches to the problems of ataxia, spasticity, spinal deformity, loss of ambulation, loss of hand function, loss of contact with the environment, feeding, irritability, and family coping are discussed. PMID- 3087185 TI - Therapeutic effects of a ketogenic diet in Rett syndrome. AB - Seven girls (age 5 to 10 years) with Rett syndrome were investigated extensively. In 6 patients elevations of blood pyruvate were found. Blood lactate levels were marginally elevated. Two patients had variably elevated blood glucose levels. Metabolic studies were otherwise normal apart from minimally elevated blood ammonia levels in 3 of 5 patients tested, 2 of whom were on valproic acid. All 7 patients had anticonvulsant resistant seizures. EEG changes included generalized slowing and multifocal spike wave discharges, and pseudo-periodic burst suppression patterns during sleep. Respiratory monitoring revealed apneic episodes only during the waking record. Six patients were below the 5th centile for weight despite normal caloric intake. Treatment with ketogenic diets, using medium chain triglyceride (MCT) oil when possible, has improved seizure control in the 5 patients who could tolerate the diet. Slight behavioral and motor improvement has occurred in these 5 patients and 6 of 7 patients on high fat diets have gained weight. With a possible defect in carbohydrate metabolism and a difficult seizure disorder, use of a ketogenic diet is logical and appears to produce clinical benefit in patients with Rett Syndrome. PMID- 3087187 TI - Music therapy for children with Rett syndrome. AB - Access to a handicapped child with Rett syndrome may be attempted through its eyes and by means of music. The receptivity for rhythm and melodies must be located within a primitive region of the hierarchical structure of the brain because even severely retarded children do respond to music. If purposefully applied with several instruments music therapy can bring about at least a temporary cessation of the stereotypic movements in children with Rett syndrome. Many years of experience attest to the feasibility of this approach. PMID- 3087188 TI - Neuropathology of Rett syndrome. AB - Autopsy studies in 8 girls with the Rett syndrome dying between 4 and 15 years showed: Diffuse cerebral atrophy/micrencephaly, with a decrease in brain weight by 13.8 to 33.8% of age-matched controls, apparently related to the duration of the disorder; Mild, but inconsistent diffuse cortical atrophy without developmental disorders apart from occasional microdysgenesis (three cases), but increased amounts of neuronal lipofuscin, and occasional mild astrocytic gliosis; Mild, but inconsistent spongy changes in cerebral and cerebellar white matter, optic nerve (two cases), and myelinated fascicles of the brainstem tegmentum, without signs of dys- or demyelination, and apparently different from the spongy myelinopathy common to aminoacidopathies; Most conspicuous was an underpigmentation of the substantia nigra which contained many fewer well pigmented neurons for age (53-73%), and fewer pigmented granules per neuron, while the total number of nigral neurons and the triphasic substructure of neuromelanin were normal for age. No pathologic changes were seen in locus coeruleus, nucleus basalis of Meynert, and nucleus dorsalis raphe; Electron microscopy of autopsy material from an 11-year-old girl showed increased amounts of neuronal lipofuscin without signs of a storage disorder. Reactive and degenerating axons in the caudate nucleus were possibly related to the nigral changes, suggesting some dysfunction of the dopaminergic nigro-striatal system, while the synaptic organization of the neostriatum appeared unaffected. Peripheral nerve from a patient dying in advanced stage showed increased numbers of unmyelinated (regenerated?) axons, with almost no demyelination and few remyelinated axons, suggesting axonal degeneration rather than hypomyelination, but exogenous factors (malnutrition) cannot be excluded. The pathogenetic mechanisms of the morphologic brain lesions and their relations to clinical and neurochemical findings in Rett syndrome are unknown and deserve further intensive investigations. PMID- 3087189 TI - Rett syndrome: some comments on terminology and diagnosis. PMID- 3087190 TI - Anatomy of Rett syndrome. AB - Rett syndrome is a clinical entity with a distinct set of signs and symptoms. Its etiology is unknown. We review here our observations in this disorder based upon clinical and polysomnographic examinations which are consistent with a developmental disorder of the monoaminergic neural system. These studies argue for a disorder of the noradrenergic, serotonergic and dopaminergic system arising in the locus ceruleus, raphe nuclei and substantia nigra, respectively. Because events of rapid eye movement sleep appear not disturbed, except for body movements, cholinergic neurons are probably not affected. Disordered physiologic states appear in a characteristic sequence with advancing age. Clinical symptoms associated with the aberrant caudally located neurons appear early and those rostrally located become manifested later. This caudalorostral developmental process attributable to early lesion of monoaminergic neurons may explain the age related sequence of symptoms of Rett syndrome. PMID- 3087191 TI - Preliminary brain autopsy findings in progredient Rett syndrome. AB - Postmortem human brain analyses have been performed to further evaluate pathogenetic aspects of the Rett syndrome. While there are no significant abnormalities with respect to amino acid concentrations in putamen, caudate nucleus, red nucleus and thalamus, the concentration of kynurenine is increased in putamen, caudate nucleus, gl. pallidus, raphe and amygdaloid n. In contrast, serotonin and its metabolite 5-hydroxyindole acetic acid are below normal levels. D2-receptor number is decreased and there is a significant drop in the concentration of the iron-binding protein ferritin. It can be concluded, that reduction of D2-receptors is due to loss of cholinergic and GABA-ergic cell bodies in the striatum or may be a response to iron deficiency. Low serotonergic and high kynurenergic activity may be of pathogenetic importance in the frequently observed cerebral seizures in Rett syndrome. PMID- 3087192 TI - Pterins in patients with Rett syndrome. AB - We have found normal concentrations of neopterin, monapterin, isoxanthopterin, biopterin and pterin in the urine of 10 patients with Rett syndrome, and normal values for total biopterin and neopterin in the blood of 4 subjects. Thus, there is no biochemical evidence of a generalized tetrahydrobiopterin deficiency in this syndrome. Since we had no opportunity so far to study cerebrospinal fluid, a defect in the metabolism of pterins in the central nervous system is not yet fully excluded. PMID- 3087193 TI - Biotin and Rett syndrome. AB - A protein load with an ensuing 20 hr fast was performed to assess the function of biotin dependent carboxylases in 3 girls with Rett syndrome. In plasma a moderate increase of ammonia and propionate was found. The fact that these discrete biochemical alterations were found in all of the patients supports earlier conclusions that further studies on biotin metabolism and carboxylase function should be performed, perhaps preferably in cerebrospinal fluid. PMID- 3087194 TI - A case of ornithine transcarbamylase deficiency with Rett syndrome manifestations. AB - We have studied an 8-year-old girl with ornithine transcarbamylase deficiency with many of the manifestations of Rett syndrome. She is profoundly mentally retarded and microcephalic after normal development in early childhood. Seizures, hyperventilation, ataxia, amimia, and "hand wringing" stereotypies are present. The distinguishing characteristic is the history of recurrent episodes of vomiting and hyperammonemic coma. This case points to the possible existence of genocopies of Rett syndrome. PMID- 3087195 TI - Chromosome studies in 10 patients with the Rett syndrome. AB - Chromosomes of white blood cells from 10 girls with the Rett syndrome, 9 of their mothers and 17 unrelated controls (5 girls and 12 women) were examined for the presence of the fragile site on Xp22 under different culture conditions. Six of the 10 Rett patients were fra(X)(p22) positive while 4 failed to express this fragile site. In the 6 patients expressing the fragile site it was present in 1 to 3% of all cells. Similarly, 5 of the mothers and 6 of the control women showed this fragile site, with a frequency of 1 to 9%. Concordance analysis showed that in the 9 mother-daughter pairs examined, 5 had concordant results while 4 of the pairs were discordant. These findings are very similar to those found in non-Rett individuals by ourselves and other investigators. These data agree with published findings that fra(X)(p22) is a common fragile site in normal individuals. Therefore, we conclude that the incidence of the Xp22 fragile site in the Rett syndrome does not differ from that found in various non-Rett individuals, including normal persons. This indicates to us that fra(X)(p22) cannot serve as a chromosomal marker for the Rett syndrome. PMID- 3087197 TI - Chromosome findings in the Rett syndrome and a test of a two-step mutation theory. AB - Chromosome findings are described in 22 girls with the Rett syndrome. One of the girls had a duplication of chromosome 6, another showed a deletion X(p22----pter) in 10% of the cells from fibroblast cultures. Fragile X(p22) was seen in 9 of the 22 girls with Rett syndrome. A relationship between the disorder and fragile X(p22) could not be proven. Family data contradict our theory of a two-step mutation as the cause of the Rett syndrome. PMID- 3087196 TI - Rett syndrome: lack of association with fragile site Xp22 and strategy for genetic mapping of X-linked new mutations. AB - The hypothesis of X-linked new mutations which might cause early abortions of hemizygous male fetuses and a dominant phenotype in heterozygous females seems the most likely genetic explanation of the Rett syndrome. This hypothesis can be reconciled with the normal sex ratio observed in sibships of patients and with the rare recurrence of this disorder in sibs or half-sibs. The latter observation can be explained by germinal mosaicism in one of the two parents. Since in 14 patients no association was found with any particular fragile site or chromosome rearrangement, we propose to map the mutated gene (or loci) on the X through a strategy based on the reconstruction of X-linked haplotypes consisting of DNA polymorphisms, and on the identification of possible crossovers in affected sisters. PMID- 3087198 TI - On the genetics of Rett syndrome: analysis of family and pedigree data. AB - Pedigree studies of 220 Rett syndrome cases (218 isolated cases, one family with affected half sisters and one family with affected sisters) tested 5 monogenic hypotheses, taking account of apparently absolute gynecotropy and healthy parents. Without increased consanguinity we found a normal sex ratio among sibs; the rate of spontaneous abortions was not increased. There is also no increase in parental conceptional age. As the patients do not propagate, transmission of a supposed gene could not be observed. The results are compatible with either an autosomal dominant mutation with complete sex limitation or (more likely) an X chromosomal dominant mutation with lethality to the males. As the probability for 2 affected sisters in one sibship differs considerably from the real incidence, alternative models should be taken into consideration and may be tested by linkage analysis. PMID- 3087199 TI - Rett syndrome--search for genetic markers. AB - We have studied 8 girls with Rett syndrome, including 2 sisters. Their ages ranged from 1 to 26 years. The youngest patient presented with developmental delay and atypical infantile spasms. The oldest was the sister of a patient followed over a period of 13 years and showed the typical history and clinical picture of Rett syndrome. DNA from white blood cells of these patients was investigated for alterations in the OTC structural gene. As compared to normal control individuals no gross alterations occur in the OTC structural genes of patients with Rett's syndrome. PMID- 3087200 TI - The genetics of Rett syndrome: the consequences of a disorder where every case is a new mutation. AB - The genetic data on Rett syndrome suggest a mutant gene acting as an X-linked dominant with lethality in the male and reproductive lethality in the female. Thus, all cases represent new mutations. The presence of two affected sisters in two of 600 families indicates the ratio of germinal mosaicism to all germinal mutants is about 1:150. After excluding propositi, a 1:1 M:F ratio of other siblings would be expected and there should be an increase in spontaneous abortion only in the germinal mosaicism families. The presence of two abortions at three months gestation in such a family suggest the Rett syndrome protein is essential to brain development at this stage of embryogenesis. Neuropathological and two-dimensional gel electrophoretic examination of the brains of aborted male fetuses in such families should provide critical evidence on the pathogenesis of the disease. Classical linkage studies cannot be done. The most parsimonious method of locating the site of the Rett syndrome gene is to do high resolution banding in all Rett syndrome cases, searching for X-chromosome deletions, or less likely, X:autosome translocations. PMID- 3087201 TI - The Rett syndrome: genetics and the future. AB - Genetic and nongenetic explanations of female-limited disease, such as the Rett syndrome, are reviewed, with emphasis on the possibility of a disturbance of late replicating X-chromosome heterochromatinization. A possible disturbance of X chromosome late-replication, as demonstrated by BUdR terminal pulse-labelling is described for a specific Rett syndrome patient. PMID- 3087202 TI - Rett syndrome bibliography. PMID- 3087203 TI - Rett syndrome: a suggested staging system for describing impairment profile with increasing age towards adolescence. AB - A four-stage construction is presented for illustrating the characteristic clinical pattern and profile over the years in the average, 'classical' rett syndrome (RS) patient. The staging system was applied and evaluated in the 29 Swedish RS cases who now have passed age 13 (median 18). We also discuss the diagnostic pitfalls we have met and the conditions that need to be considered in the differential diagnosis. PMID- 3087204 TI - Rett syndrome--natural history in 70 cases. AB - We evaluated, at our institute, 70 females with Rett syndrome between 2 1/2 to 34 1/2 years old. This provided an opportunity of observing the natural history of this condition. The evolution of a subacute encephalopathy of very early onset, maximizing in the second year of life, with slow recovery and devastating sequelae, was recognized. The hyperorality, visual auditory and tactile agnosia with aphasia and seizures resembled symptoms described in human Kluver Bucy syndrome. Over interpretation of behavioral abnormalities as seizures was common. Scoliosis was not a necessary concomitant of age. A consistent biochemical or neurophysiological abnormality was not detectable in understanding the cause and pathogenesis of this disease process. Life span appears to be unaffected though life tables have not yet been established. PMID- 3087205 TI - Rett syndrome--observational study of 33 families. PMID- 3087206 TI - A study of the natural history of Rett syndrome in 23 girls. AB - We have studied 23 patients with Rett syndrome with particular reference to the character and natural history of the clinical disorder. We found a prevalence of 0.8 per 10,000 girls 0-14 years in the region from which cases came. We consider that the disorder of tone, posture and movement is extrapyramidal in nature and suggest that the gradual emergence of its fully developed pattern leads to the familiar regression in skills on presentation. We have not found proof of dementia at this stage but rather of severe mental handicap. PMID- 3087207 TI - Rett syndrome at an institution for the developmentally disabled. AB - Rett syndrome (RS) is a condition apparently limited to females characterized by normal early development followed by the abrupt loss of acquired function and beginning autistic behavior in late infancy. Manifestations in RS include decelerating head growth, unusual "hand-writing" movements, gait apraxia, neuromuscular tone disturbance, and seizures. No biochemical, hematologic, cytologic, or cytogenetic procedures have been shown to confirm the diagnosis of RS. With the exception of one family with 2 affected half-sisters, all cases have been sporadic. Six profoundly retarded residents of Central Wisconsin Center have manifestations of RS. Three are microcephalic and 3 have head circumferences at or below the 10th centile. All have seizures or abnormal EEG findings and all were ascertained on the basis of characteristic hand movements. No case of precocious puberty was observed. Two patients had severe scoliosis which was surgically treated. Detailed neuropathologic examination should be sought for every case of RS. The development of clearly defined minimal diagnostic criteria and the establishment of an international registry are desirable. PMID- 3087208 TI - Rett syndrome: studies of 13 affected girls. AB - This is a presentation and discussion of clinical and laboratory data obtained on 13 girls with Rett syndrome, a progressive neurological disorder. The condition is thought to be far more prevalent than earlier reported. Family history in one patient showed presence of abnormal hand movements, increasing spasticity and psychomotor retardation in a paternal great grandaunt who died at 7 years. In the absence of chromosomal or biochemical markers, the characteristic disorder of hand movements can be used to distinguish this entity from other mental retardation, cerebral palsy and autism conditions. This report addresses the uniformity of clinical expression and highlights the differences between autism and Rett syndrome. Precocious puberty and respiratory alkalosis were not found in our patients. Feeding disorders were commonly present, and are often difficult to manage. The importance of diagnosis is emphasized as it influences long term management. PMID- 3087209 TI - Tube feeding: is diarrhea inevitable? PMID- 3087210 TI - Treatment of severe androgen excess due to ovarian hyperthecosis with a long acting gonadotropin-releasing hormone agonist. AB - A 31-year-old nulligravid patient presented with irregular menses, severe hirsutism, and infertility. Evaluation revealed marked increases of serum androstenedione and testosterone levels and a possible ovarian mass. At operation a cystic teratoma was removed from the left ovary and bilateral wedge resection revealed severe ovarian hyperthecosis. After operation only a transient decrease of androstenedione and testosterone was noted and the patient failed to ovulate or improve clinically. Subsequently a long-acting gonadotropin-releasing hormone agonist was administered daily for 6 months, which reduced circulating delta 4 steroids and estrogens to levels approximating those of castrated women. Immediately after discontinuation of treatment, ovulation induction was successfully achieved with human menopausal gonadotropin. This report introduces a new therapeutic approach to the problem of severe ovarian hyperthecosis and may provide an opportunity for childbearing in these patients. PMID- 3087211 TI - Nutritional support and the occupational therapist's role. AB - Nutrition, although important, is often overlooked during hospitalization. At Grant Hospital of Chicago, a nutritional support team is trained in recognizing, assessing, and managing nutritional disorders. The occupational therapist member of this team works to enhance patients' functional independence physically and emotionally. Knowledge of nutrition is necessary for all health professionals when dealing with the total person. PMID- 3087212 TI - Cut marks on the Bodo cranium: a case of prehistoric defleshing. AB - Cut marks were discovered on the Middle Pleistocene Bodo cranium from Ethiopia. The cut marks most closely resemble experimental damage caused by the application of stone tools to fresh bone. This discovery constitutes the earliest solid evidence for intentional defleshing of a human ancestor and offers new research avenues for the investigation of early hominid mortuary practices. PMID- 3087213 TI - Role of intracellular calcium in cellular volume regulation. AB - We investigated the role of intracellular calcium in epithelial cell volume regulation using cells isolated from the toad urinary bladder. A suspension of cells was prepared by treatment of the bladder with collagenase followed by ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid. The cells retained their ion-transporting capabilities: ouabain (1 mM) and amiloride (10 microM) inhibited cellular uptake of 86Rb and 22Na, respectively. Using a Coulter counter to measure cellular volume, we found that we could swell cells either by reducing the extracellular osmolality or by adding the permeant solute urea (45 mM) isosmotically. Under both conditions, cells first swelled and then returned to their base-line volume, in spite of the continued presence of the stimulus to swell. Volume regulation was inhibited when cells were swelled at low extracellular [Ca] (100 nM) and was retarded in cells preloaded with the calcium buffer quin 2. Swelling increased the intracellular free calcium concentration ([Ca]i), as measured by quin 2 fluorescence: [Ca]i increased 35 +/- 9 nM (n = 6) after hypotonic swelling and 42 +/- 3 nM (n = 3) after urea swelling. Reducing extracellular [Ca] to less than 100 nM prevented the swelling-induced increase in [Ca]i, suggesting that the source of the increase in [Ca]i was extracellular. This result was confirmed in measurements of cellular uptake of 45Ca: the rate of uptake was significantly higher in swollen cells compared with control (1.1 +/- 0.2 vs. 0.4 +/- 0.1 fmol . cell-1 X 5 min-1). Our experiments provide the first demonstration that cellular swelling increases [Ca]i. This increase is likely to play a critical role in cellular volume regulation. PMID- 3087214 TI - Dexamethasone inhibits prostaglandin release from rabbit coronary microvessel endothelium. AB - The effects of dexamethasone on prostaglandin secretion by cultivated rabbit coronary microvascular endothelial (RCME) cells were investigated. Incubation of RCME cells with dexamethasone resulted in a time- and concentration-dependent decrease in prostaglandin accumulation in the culture media and reduced basal and A23187-stimulated prostaglandin (PG) E2 and 6-keto-PGF1 alpha release. The maximal effects of dexamethasone (50-80% inhibition) were achieved after 16-18 h of incubation with the steroid at a final concentration of 10(-7) M. The effects of dexamethasone treatment were partially reversed 24 h after removal of the steroid from the culture media. Dexamethasone treatment did not reduce arachidonic acid-stimulated prostaglandin synthesis, indicating that the level of inhibition was proximal to that of cyclooxygenase. The inhibitory effects of dexamethasone could be prevented by pretreatment of the RCME cells with actinomycin D or cycloheximide, suggesting a requirement for protein synthesis in the inhibitory action of dexamethasone. Conditioned media from dexamethasone treated cells contained a factor that inhibited porcine pancreatic phospholipase A2 (PLA2) in vitro. Transfer of conditioned media from dexamethasone-treated cells to untreated cells did not reduce basal or stimulated prostaglandin release; in contrast, a stimulatory action was consistently observed. Adherence of rabbit peripheral polymorphonuclear leukocytes (PMN) to RCME cells was reduced when the leukocytes were pretreated with 10(-7) M dexamethasone (4 h). However, dexamethasone pretreatment of the RCME cells did not significantly effect granulocyte adhesion. Thus coronary microvascular endothelial cell prostaglandin production is regulated by glucocorticoids, and glucocorticoid-pretreated microvascular endothelial cell release an inhibitor of PLA2 activity into the culture media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087215 TI - Relation between plasma and tissue parameters of leucine metabolism in fed and starved rats. AB - By use of a primed continuous infusion of [1-14C]leucine, we investigated parameters of leucine metabolism in plasma, expired air, and tissues of fed and 48-h starved rats. The ratios of muscle to plasma specific activity of alpha ketoisocaproate (KIC) in fed and starved rats were not significantly different from 1. The ratio of muscle to plasma specific activity of leucine was also not significantly different from 1 in fed rats, but was significantly lower than 1 in starved rats. The rate of leucine oxidation was 28-34% higher when calculation was based on plasma KIC rather than leucine specific activity. However, starvation significantly increased the rate of leucine oxidation with either specific activity. The rates of leucine incorporation into whole-body protein, calculated as the difference between plasma leucine turnover and oxidation, were unaffected by starvation, but the incorporations into total protein measured directly were significantly decreased in liver and muscle. We conclude that leucine or KIC specific activity in muscle is better predicted by plasma KIC than leucine specific activity, and the difference between rates of plasma leucine turnover and oxidation does not appear to be a valid measurement of leucine incorporation into whole-body protein. PMID- 3087217 TI - Kinetics of zinc uptake and exchange by primary cultures of rat hepatocytes. AB - The kinetics of 65Zn2+ uptake and exchange by hepatocytes in primary culture have been examined in detail to provide a basis for analyzing hormonal regulation of hepatic zinc metabolism. 65Zn2+ uptake was found to be a biphasic process. The slow phase represents an exchange between Zn2+ in the medium and preexisting, intracellular zinc pools. This exchange rate was saturable with a medium zinc concentration of 9.5 microM eliciting one-half the maximum exchange rate and a maximum exchange rate of 9.9 pmol Zn2+ . min-1 . mg protein-1 in the presence of bovine serum albumin. In the absence of albumin, a secondary, nonsaturable uptake rate was observed. The slow phase was relatively selective, and of the divalent transition metal ions tested, only Cd2+ and Mn2+ caused inhibition. The rate of exchange suggests total hepatocyte zinc has a turnover rate of approximately 30 h. The fast phase of 65Zn2+ reflects net Zn2+ accumulation into a labile pool. The initial rates for this process were too fast to be measured accurately, but steady-state measurements allowed determination of the labile pool size. The pool dimensions saturated in the presence [Kapp = 28.6 microM; pool capacity = 0.44 nmol Zn2+/mg protein] and absence [Kapp = 11.8 microM; pool capacity = 0.34 nmol Zn2+/mg protein] of bovine serum albumin. Kinetics and equilibria of Zn2+ uptake into the labile pool suggest that the latter acts as a source of Zn2+ for the slow-exchange phase. Dexamethasone stimulated slow Zn2+ exchange and also increased the labile pool size. The data suggest physiological factors alter hepatic zinc metabolism by influencing both intracellular Zn2+ pools. PMID- 3087216 TI - Sex-related differences in GH secretion in rat using reverse hemolytic plaque assay. AB - It is not known whether enhanced growth hormone (GH)-releasing factor (GRF) stimulated GH release observed in the male reflects differences in somatotrope numbers and/or secretory response to GRF. We addressed this question by using the hemolytic plaque assay which allows quantification of hormone secretion by single pituitary cells. Time-course studies and GRF-GH concentration-response relationships (0.01, 0.1, 1, 10, 100, 1,000 nM GRF) in age-matched male and diestrous day 2 female rats were compared by quantitating the percent of GH plaque-forming cells, and measuring the plaque areas. The male pituitary contained a greater percent (P less than 0.05) of somatotropes (% of plaque forming cells 45 +/- 2 vs. 27 +/- 4% in the female; mean +/- SE). GRF induced a greater concentration-dependent increase in plaque areas in the male. Maximal responses were attained at 10 nM GRF in both sexes. However, mean maximal plaque area was significantly greater (P less than 0.001) and the EC50 was significantly lower (P less than 0.05) in the male (0.25 +/- 0.09 vs. 1.78 +/- 0.64 nM in the female). The data suggest that the greater percent of somatotropes in the male and greater secretory capacity and sensitivity to GRF may contribute to sex related differences in GH secretion in the rat. PMID- 3087218 TI - Production of platelet-activating factor in glomeruli and cultured glomerular mesangial cells. AB - Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) results in contraction of isolated glomeruli and cultured mesangial cells and concomitantly causes release of arachidonic acid and prostaglandin E2 (PGE2) formation. The kidney and isolated glomeruli can also generate material that has PAF bioactivity. We therefore examined the capacity of isolated renal glomeruli and cultured glomerular mesangial cells from rats to form PAF. Both isolated glomeruli and cultured mesangial cells transformed 1-O-alkyl-2-lyso-sn-glycero-3 phosphocholine ([3H]lyso-PAF) into a labeled product comigrating both on thin layer chromatography (TLC) and high-pressure liquid chromatography (HPLC) with authentic PAF. Using rabbit platelet aggregation as bioassay for PAF, we found that isolated glomeruli produced 4 +/- 2 pmol/mg glomerular protein of PAF-like material, and mesangial cells produced 30 +/- 8 pmol/mg cell protein when stimulated with A23187 (10(-5) M) for 30 min. The major species of the PAF material produced by mesangial cells was identified as 1-O-hexadecyl-2-acetyl-sn glycero-3-phosphocholine after HPLC separation, followed by fast atom bombardment and gas chromatography-mass spectrometry. These results show that glomerular mesangial cells can produce PAF, which could contribute locally to the regulation of glomerular function. PMID- 3087219 TI - Thyrotropin releasing hormone in hypovolemia: a hemodynamic evaluation in the rat. AB - In the present study the effects of thyrotropin releasing hormone (TRH) and its stable analogue, CG3703, on cardiac output (thermodilution, Cardiomax) and regional blood flow (BF; directional pulsed Doppler technique) were investigated in hypovolemic hypotension in the rat. In urethan-anesthetized rats TRH (0.5 or 2 mg/kg ia) or CG3703 (0.05 or 0.5 mg/kg ia) reversed the bleeding (27% of the blood volume)-induced decreases in mean arterial pressure (MAP) and cardiac index (CI) and increased the heart rate (HR) and total peripheral resistance index (TPRI) in a dose-related manner. In the conscious rat exposed to a 45% hemorrhage, CG3703 (0.5 mg/kg ia) significantly raised MAP, HR, and TPRI with maximum changes of +67 +/- 6 (SE) mmHg, +123 +/- 30 beats/min, and +101 +/- 2%, respectively, CG3703 (0.5 mg/kg ia) also further enhanced the hemorrhage-induced reduction of hindquarter, mesenteric, and renal BF. The changes in BF in saline treated vs. CG3703-treated rats 2 h after the bleeding were -32 +/- 6 vs. -55 +/- 6% (P less than 0.001) in hindquarter, -9 +/- 8 vs. -61 +/- 11% (P less than 0.001) in mesenteric, and -2 +/- 9 vs. -33 +/- 9% (P less than 0.01) in the renal artery; the changes in vascular resistance +30 +/- 7 vs. +309 +/- 167% (P less than 0.001) in hindquarter, -4 +/- 8 vs. +349 +/- 244% in the mesenteric, and -10 +/- 9 vs. +80 +/- 10% (P less than 0.01) in the renal artery. The survival rate after the 45% hemorrhage was significantly reduced by both TRH and CG3703.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087221 TI - Reduced osmotic and nonosmotic release of vasopressin after meclofenamate in the conscious dog. AB - Both in vivo as well as in vitro experiments suggest that prostaglandins (PG) may influence arginine vasopressin (AVP) release. Recent studies on conscious dogs have shown that cyclooxygenase inhibition with meclofenamate reduces basal AVP release as well as AVP release in response to hypoxia. The current experiments were performed in order to test whether PG synthesis inhibition affects osmotic- and nonosmotic-stimulated AVP release in a similar manner. Osmotic AVP release was tested by slowly infusing hypertonic saline intravenously in water-diuresing dogs and serially sampling plasma for AVP concentration. Experiments were performed both with and without meclofenamate (2 mg/kg and 2 mg X kg-1 X h-1 iv) pretreatment. AVP release to a comparable osmotic stimulus was greatly reduced after meclofenamate administration. Nonosmotic AVP release was tested by inducing systemic hypotension with an intravenous infusion of nitroprusside. Hypotension was associated with an increase in AVP concentration, which was partially blunted after meclofenamate administration. Experiments performed with only a saline vehicle administered showed no decrease in AVP release in response to comparable hypotension. The findings of these studies suggest that endogenous PG may be involved in both osmotic and nonosmotic AVP release in the conscious dog. PMID- 3087222 TI - Outpatient treatment of patients with substance abuse and coexisting psychiatric disorders. AB - Thirty-two patients with coexisting substance abuse and other psychiatric disorders were treated in a unique outpatient pilot program that used techniques drawn from both psychiatric and substance abuse treatment. Eleven patients remained in treatment for 3 or more months, and seven completed a year or more of treatment. Severity of associated psychiatric illness did not affect retention in treatment. Drug-abusing patients and those with personality disorders dropped out quickly; patients with a history of reliable outpatient treatment involvement tended to remain in treatment. Treatment retention was associated with reduced hospital utilization. The authors suggest guidelines for management of patients with coexisting substance abuse and other psychiatric disorders. PMID- 3087220 TI - Prostaglandins do not mediate arteriolar oxygen reactivity. AB - The hypothesis that prostaglandins mediate arteriolar O2 reactivity was tested by assessing the effects of cyclooxygenase and phospholipase A2 inhibitors on the O2 responses of arterioles in superfused hamster cheek pouch and hamster and rat cremaster muscle preparations by use of intravital microscopy. Superfusion of these three preparations with the cyclooxygenase inhibitor indomethacin (50 microM) completely inhibited the response of the vessels to exogenous arachidonic acid but had no effect on the arteriolar constriction induced by elevation of superfusion solution PO2 from 15 to 150 mmHg. Similar results were obtained in the hamster cheek pouch with another cyclooxygenase inhibitor, meclofenamate, or when indomethacin (5-50 mg/kg) was administered systemically. Dexamethasone (12.7 microM) and quinacrine (10 microM), two reported inhibitors of phospholipase A2, also had no significant effect on arteriolar O2 reactivity in the cheek pouch. At 50 microM, quinacrine significantly depressed arteriolar reactivity to O2, adenosine, methacholine, and phenylephrine, suggesting nonspecific effects. These data do not support the hypothesis that prostaglandins mediate arteriolar O2 reactivity. PMID- 3087223 TI - Lithium potentiation of neuroleptic-related extrapyramidal side effects. PMID- 3087225 TI - [Metabolic effects of postoperative intravenous administration of carbohydrate calories exclusively in the form of sorbitol]. PMID- 3087224 TI - Immunological and genetic factors influencing pregnancy and development. AB - Hypotheses concerning reproductive competence focus on immunological and genetic mechanisms. The immunological hypothesis involves arguments that an immune response is necessary for implantation (or at least increased reproductive capacity), the antibody response to the placental antigens is composed of "blocking" antibodies, immunosuppressive factors are produced during pregnancy, and HLA antigen sharing in humans having chronic spontaneous abortions (CSA) causes a decreased immune response. The most potent antigen on the placenta is a class I molecule different from the classical transplantation antigens: Pa in the rat and TLX in the human. The genetic hypothesis states that CSA may be due to the presence of major histocompatibility complex (MHC)-linked, recessive lethal genes in the fetus and that the sharing of HLA antigens is just a marker for this segment of chromosome. Recessive lethal genes linked to the MHC exist in mice and rats and possibly in humans. They could act by themselves to cause fetal loss, or they could act epistatically with nonMHC lethal genes. This type of interaction occurs in the rat between the MHC-linked grc and Tal or Hre. Recent work in our laboratory has shown that the grc also increases susceptibility to the development of cancer following the feeding of a chemical carcinogen. This unique finding presents a new and powerful approach to exploring the relationship between embryogenesis and carcinogenesis. PMID- 3087226 TI - Intensive factor replacement for management of chronic synovitis in hemophilic children. PMID- 3087227 TI - An extracellular body of plasma cell origin in inflammatory infiltrates within the dermis. AB - During examination of a biopsy specimen of skin by conventional microscopy, numerous round, basophilic, extracellular bodies suggestive of fungal organisms were seen in the dermis. Further evaluation and special staining suggested that their origin was from the plasma cells. Examination of biopsy material from 48 patients with cutaneous plasma cell infiltrates revealed similar bodies in 20 cases (42%). Sizes of bodies varied, the largest being 5.0 microns in diameter. In every case, staining reactions were identical to those of plasma cell cytoplasm. Immunoperoxidase methods showed that, like plasma cells, the bodies contained either kappa or lambda light chains. In one case of plasmacytoma associated with multiple myeloma, both the bodies and the surrounding neoplastic cells stained for kappa chains only. Electron microscopy revealed rounded structures composed of aggregates of rough endoplasmic reticulum, which contained varying amounts of moderately electron-dense material within the cisternae. Fragmented plasma cells were also seen. The evidence suggests that plasma cell bodies are distinct from Russell bodies. They probably form as a result of trauma during processing of tissue, but could also represent a degenerative process in vivo. They should be distinguished from pathogenic micro-organisms and other extracellular bodies. PMID- 3087229 TI - The etiology of lichen planus. A hypothesis. PMID- 3087228 TI - Congenital hemangiopericytomas of skin. AB - A case of multiple congenital hemangiopericytomas of skin treated by surgical excision is presented. No recurrence of the lesions has occurred after a period of 2 years. PMID- 3087231 TI - [Alfentanil as the last dose (on top) in neuroleptanesthesia with fentanyl. Pharmacokinetics and pharmacodynamics with reference to the cortical effect]. AB - Due to its predictable duration of action, its low volume of distribution in the organism (muscle, fat tissue, skin) and a corresponding low terminal elimination half life (t 1/2 beta), alfentanil seems suitable for use as the last dose of opioid given during NLA. In order to compare the efficacy of this regimen, patients (n = 10) during routine-NLA (induction 0.3 mg/kg etomidate, 140 micrograms/kg droperidol, 5 micrograms/kg fentanyl with a maintenance dose of 2 micrograms/kg when necessary and mechanical N2 O/O2 = 2:1 ventilation) received alfentanil (20 micrograms/kg) as the last opioid, while another set of patients (n = 5) received fentanyl (1.5 micrograms/kg). For recording of vigilance continuous EEG power spectra were derived (position Fpz--C3), and in addition minute volume was monitored postoperatively. After the last dose of the opioid, alfentanil--and fentanyl--blood plasma levels were determined every 10 min over a period of 100 min Vigilance, i.e. the sensitivity of the organism in responding to a stimulus, was significantly higher in the "on-top"-alfentanil group. This was derived from the high power in fast frequency domains, beta (greater than 460%) and alpha (greater than 34%) compared to routine NLA in the post op. period. No significance was observed among both groups in regard to postop. respiratory minute volumes and fentanyl plasma levels. There was no correlation between power in the various frequency bands (delta, theta, alpha and beta), postoperative respiratory minute volumes and corresponding plasma levels of fentanyl. Due to a higher state of postoperative vigilance, alfentanil is considered a suitable alternative as the last opioid during narcotic anaesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087230 TI - Antigen-induced bronchial anaphylaxis in actively sensitized SD rats. Effects of glucocorticoid treatment. AB - We examined the effects of glucocorticosteroids (GCS) on antigen-induced bronchial anaphylactic reactions (BAR) in SD rats immunized with ovalbumin (OA) and alum. The animals were treated with vehicle, budesonide (BUD), dexamethasone (DEX), or hydrocortisone (HC) at various times before intravenous (i.v.) antigen challenge. The drugs were administered either intraperitoneally (i.p.) or intratracheally (i.t.); the BAR was elicited by a low or by a high challenge dose of antigen. A BAR elicited by a low challenge dose of antigen was reduced in a dose-dependent way by all GCS after i.p. administration; at 1 mg/kg, BUD and DEX significantly reduced BAR and at 50 mg/kg all three of the examined compounds inhibited the BAR by 50% or more. For BUD, maximum effect was recorded when it was given 12 h before test. There was only a slight variation in the inhibitory effects of the GCS with immunization conditions of test animals. I.t. instillation of the drugs did not markedly increase their inhibitory capacity as compared to i.p. administration. BAR elicited by a high antigen dose was at best marginally affected by the GCS when given either i.p. or i.t. Thus, antigen induced airway reactivity in rats can be reduced by GCS treatment provided that this is performed sufficiently long before the test and that the challenge dose of antigen is not too high. PMID- 3087232 TI - Chlorophyll: an efficient detector of electronically excited species in biochemical systems. AB - Micelle-solubilized chlorophyll efficiently detects electronically excited species generated in enzymatic systems. In most, if not all, systems the chemiexcited species is formed in the triplet state; chlorophyll fluorescence is observed as result of energy transfer. Red emission can also be elicited from chlorophyll in chloroplasts or bound to microsomes. PMID- 3087233 TI - Evaluations of tyrosine apodecarboxylase assays for pyridoxal phosphate. AB - The alternate procedures used in the tyrosine apodecarboxylase assays for pyridoxal 5'-phosphate were evaluated to determine optimal conditions. Two preparations of tyrosine apodecarboxylase from Streptococcus faecalis were used: a cell suspension and a partially purified cell-free form. The activity of the decarboxylase was measured in two different assays using [14C]tyrosine or [3H]tyrosine as substrate. The presence of serum proteins caused greater inhibition of the assay for serum pyridoxal phosphate using [14C]tyrosine as substrate than the assay with [3H]tyrosine. In contrast, addition of deproteinized serum extract did not appear to inhibit either assay. The rate of reconstitution of the apodecarboxylase in the cell suspension was at least four times slower than that of the cell-free enzyme. The rate of reconstitution of the cell-free enzyme was faster in acetate than in citrate buffer. Inorganic sulfate or phosphate, at normal plasma concentrations, did not alter either the reconstitution rate of tyrosine decarboxylase or the final activity obtained in the assays using either substrate. The tyrosine apodecarboxylase assay for pyridoxal phosphate can be optimized by using deproteinized sera or plasma and incubating the cell-free apoenzyme with the coenzyme in acetate buffer for a time sufficient to obtain maximum reconstitution. PMID- 3087234 TI - Long-lived enzymatic metabolites of thromboxane B2 in the human circulation. AB - Thromboxane A2, a potent vasoconstrictor and platelet agonist, is an evanescent cyclooxygenase product of arachidonic acid. Assessment of thromboxane biosynthesis commonly relies upon analysis of the stable but biologically inactive hydration product, thromboxane B2. However, measurement of this compound in plasma is readily confounded by platelet activation ex vivo. We have identified 11-dehydro-thromboxane B2, 11-dehydro-13,14-dihydro-15-keto thromboxane B2, and 2,3-dinor-thromboxane B2 as enzymatic products of infused thromboxane B2 in the human circulation. Biosynthesis of deuterated standards permitted the development of quantitative analyses for these compounds, employing capillary gas chromatography-negative ion chemical ionization-mass spectrometry. We thus established that the postinfusion half-lives of 11-dehydro-thromboxane B2 and the keto-dihydro metabolite approximated 1 hour, while that of the dinor metabolite ranged from 15 to 17 min. Combined analysis of short- and long-lived enzymatic metabolites of thromboxane B2 promises to bypass the problem of ex vivo platelet activation and enhance the likelihood of relating a discreet clinical event to an alteration in the biosynthesis of thromboxane A2 in the human circulation. PMID- 3087235 TI - Liquid chromatography of tin-reduced technetium hydroxyethylidene diphosphonate complexes for on-line spectral characterization and double isotope labeling. PMID- 3087237 TI - Treatment of asthenozoospermia with HCG. AB - 30 patients with isolated asthenozoospermia received a treatment with 5000 I.U. Human-Chorionic-Gonadotropin (HCG) a week intramuscularly for twelve weeks. Pretreatment basal levels of FSH, LH and testosterone were in normal or low normal range. 16 males responded to therapy, the total motility of spermatozoa increased significantly from 34% to 40%. In spite of a decreased sperm density and morphologic quality 6 pregnancies occurred. This result strengthens the interpretation, that sperm motility is the most important factor for fertilization. HCG therapy must be considered as an additional approach for treating motility disturbances, especially in cases with high sperm densities. PMID- 3087236 TI - Isosexual precocious pseudopuberty secondary to a testosterone-secreting Leydig cell testicular tumour: true isosexual development early after surgery. AB - The paper reports on a 6-year-old boy with precocious pseudopuberty due to androgen hypersecretion by a testicular interstitial cell tumour. Steroidogenesis, characterized by high testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone and 17-hydroxyprogesterone plasma levels, was not modified by ACTH, dexamethasone or HCG administration. Gonadotropins were subnormal and unresponsive to LRH stimulation. TSH and prolactin levels were normal both in basal and dynamic conditions. The hormonal profile progressively returned to prepubertal value and persisted normal for 6 months after removal of the tumour. The patient entered puberty spontaneously at 7,6/12 years showing a normal pubertal basal and LRH stimulated FSH and LH and a pubertal circadian rhythm of both gonadotropins and testosterone. PMID- 3087238 TI - Hemodynamic responses to alfentanil in halothane-anesthetized dogs. AB - Alfentanil is an opioid that has been used both as a sole anesthetic and in conjunction with other inhalation anesthetics. However, its effects on myocardial performance and regional blood flow are not clearly known. Using sonomicrometry and radioactive microsphere techniques, we examined the hemodynamic responses to alfentanil when given as a loading dose (45 micrograms/kg) followed by continuous infusion (3 micrograms X kg-1 X min-1) in dogs anesthetized with halothane. Similar plasma levels of alfentanil were observed after the loading and infusion doses, and both techniques of administration produced a significant reduction in arterial pressure without change in global or regional function of the left ventricle. Although cardiac output and left ventricular end-diastolic pressure remained unchanged, heart rate and systemic vascular resistance decreased significantly after the loading dose and recovered slightly when alfentanil was infused continuously. Despite the systemic hypotension, alfentanil did not alter perfusion to the heart, brain, muscle, and skin; however, blood flow to the renal cortex and the arterial supply to the liver decreased by 25 and 60%, respectively. Reduction in blood flow to the kidneys and the liver suggests that alfentanil should be used with caution when normal function of these organs is in question. PMID- 3087240 TI - Resting metabolic rate of the critically ill patient: measured versus predicted. AB - Critically ill patients requiring mechanical ventilation are particularly susceptible to malnutrition. A knowledge of the energy requirements of these patients is essential in designing nutritional regimens. This study examines 45 resting energy-expenditure measurements performed in a group (n = 40) of postoperative, critically ill patients who were hemodynamically stable, noncomatose, and receiving mechanical ventilation. It examines in particular to what degree the resting energy expenditure of such patients can be predicted using the Harris-Benedict and Aub-Dubois formulae. Resting energy expenditure was measured using indirect calorimetry. There was only a moderate correlation between measured resting energy expenditure and that predicted using the Harris Benedict (r = 0.57) and Aub-Dubois (r = 0.59) formulae. There was little correlation between the ratio of the measured to the predicted (Harris-Benedict) resting energy expenditure and age, or the ratio of actual to ideal body weight and body weight. The measured resting energy expenditure differed widely (70 140%) from predicted, reflecting the many complex factors that influence these patients' metabolic rate. The role of standard predictive formulae in such patients is as an arbitrary reference point to be used to define hypermetabolism (measured greater than predicted) and hypometabolism (predicted greater than measured). PMID- 3087239 TI - Plasma drug binding: implications for anesthesiologists. PMID- 3087241 TI - Prophylactic nitroglycerin infusions during coronary artery bypass surgery. AB - The effects of prophylactic infusion of 1 microgram X kg-1 X min-1 nitroglycerin (NTG) on the incidence of ischemia, hypertension, hypotension and perioperative myocardial infarction were studied in 81 patients during coronary artery bypass grafting (CABG). Forty-one patients (Group 1) received NTG and 40 patients (Group 2) received placebo. All patients received fentanyl for anesthesia and pancuronium. Mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), heart rate (HR), and cardiac output (CO) were measured before and after induction of anesthesia, after intubation, before and after chest incision, after sternotomy, after the pericardium was opened, and during normothermic cardiopulmonary bypass. Myocardial ischemia and infarction were diagnosed from the ECG, hypertension was defined as a 20% increase in MAP, and hypotension was defined as a 20% decrease in MAP compared with preinduction values. No significant differences between Groups 1 and 2 in HR, PCWP, or CO were seen. MAP was significantly lower in Group 1 than Group 2 (P less than 0.05) before chest incision, but increased to levels equal to Group 2 after sternotomy. Hypertension occurred in 32 Group 2 patients and 25 Group 1 patients (0.05 less than P less than 0.1). Group 1 patients had 0.95 +/- 0.14 episodes per patient of hypertension, while Group 2 patients had 2.10 +/- 0.31 episodes (P less than 0.05). Hypotension occurred in 20 Group 1 patients but only six Group 2 patients (P less than 0.05). There was no difference in the incidence of ischemia. In Group 1, nine patients (22%) had ECG changes of ischemia, while 12 patients in Group 2 (30%) had ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087242 TI - End-tidal PCO2: should it be a standard of care in obstetric anesthesia? PMID- 3087243 TI - End-tidal CO2 analyzers in proper positioning of the double-lumen tubes. PMID- 3087245 TI - Monoclonal antibodies to bovine blood group antigens. AB - Hybridomas were made by fusing mouse myeloma cells with spleen cells from mice immunized with bovine red cells. Sixteen cloned lines which secreted haemolytic monoclonal antibodies reacting with antigens in the A, B, F, Z and S blood group systems were established; one of the antibodies identified a new factor in the B system. Extensive tests on red cells from 1000 animals indicated that several of the antibodies are suitable for use in routine blood typing; others are of potential use for genetic studies of the bovine blood group systems. PMID- 3087244 TI - [Parenteral feeding in the complex treatment of a patient with post-subtotal resection of the small intestine complicated by an intestinal fistula and peritonitis]. PMID- 3087246 TI - Sarcocystis infections in mule deer (Odocoileus hemionus) in Montana and the descriptions of three new species. AB - Four structural types of sarcocysts of Sarcocystis were found in skeletal muscles of mule deer in Montana. Type I sarcocysts were thin walled (1 to 3 micron) and belonged to S hemionilatrantis. Types II to IV sarcocysts were thick walled (2 to 10 microns) and new names were proposed for them. Type II sarcocysts with long villar projections were named S hemioni. Type III sarcocysts with club-shaped villi of uneven thickness were named S youngi. Type IV sarcocysts with walls of uneven thickness and containing hair-like protrusions were named S americana. PMID- 3087247 TI - Trypanosoma cruzi from wild raccoons in Oklahoma. AB - Trypomastigotes of Trypanosoma cruzi were detected in the blood of 5 of 8 wild adult raccoons which were live-trapped in Tulsa, Okla. Organisms were isolated in diphasic blood agar medium and maintained in Vero cell cultures. Inoculated mice exhibited transient parasitemias without tissue involvement. Amastigote forms occurred within Vero cells. This is the first report of naturally occurring T cruzi infection of wild mammals in Oklahoma. PMID- 3087248 TI - Results of project support nurses in long-term care. PMID- 3087249 TI - The glutathione redox cycle as a defense system against hydrogen-peroxide-induced prostanoid formation and vasoconstriction in rabbit lungs. AB - Leukocyte-derived oxidants have been described as causing vasoconstriction and edema formation in isolated lungs. In the present study, dose-dependent and reversible pressor responses were achieved reproducibly by injection of hydrogen peroxide (H2O2) into the pulmonary artery of blood-free, perfused, isolated rabbit lungs in a dose-dependent manner. The pressor responses were accompanied by an instantaneous release of thromboxane A2 and a more delayed but quantitatively larger release of prostaglandin I2 into the recirculating perfusion fluid. There was no release of potassium or LDH, indicating the absence of overt cell damage. The H2O2-induced pressor responses were blocked by indomethacin (cyclooxygenase inhibitor), imidazole (inhibitor of thromboxane synthetase), mepacrine (phospholipase inhibitor), and W7 and trifluoperazine (agents that interfere with calcium-calmodulin function). Treatment with 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU) dose-dependently inhibited the lung glutathione reductase activity and augmented the metabolic (prostanoid release) and functional (vasoconstriction) responsiveness of the pulmonary vascular bed to H2O2. Application of 1-(2-chloroethyl)-1-nitrosourea (CCNU), a control to BCNU, and inhibition of catalase activity by aminotriazole did not increase the sensitivity to externally applied H2O2. We conclude that calcium-calmodium function and thromboxane generation may be involved in the pulmonary vasoconstrictive response to H2O2 and that the lung glutathione redox cycle is active in limiting the responsiveness of the pulmonary vascular bed to externally generated H2O2. PMID- 3087250 TI - Patterns of cell proliferation during recovery from oxygen injury. Species differences. AB - Do rats, mice, hamsters, and marmosets respond differently to acute lung injury? Animals of each species were exposed to 100% oxygen for 48 h, then osmotic pumps, which released 3H-thymidine for a 1-wk period, were implanted. The labeling index (LI) (cells labeled/total cells counted) was increased in all 4 species. Repair in rats was manifested by a high LI, dominated by endothelial cell proliferation. Mice and hamsters had a lower LI, which was dominated by type II pneumocyte proliferation in mice, whereas in hamsters, macrophages and pneumocytes proliferated. The pattern of cell proliferation in marmosets most resembled that seen in mice. PMID- 3087251 TI - A ten-year experience with fiberoptic bronchoscopy for mycobacterial isolation. Impact of the Bactec system. AB - From January 1974 to December 1983, positive mycobacterial isolates from all sources were reviewed to determine the impact of fiberoptic bronchoscopy (FB) on retrieval and identification of these organisms. There were 112 patients with positive cultures obtained during FB, 25 with Mycobacterium tuberculosis and 87 with mycobacteria other than tuberculosis (MOTT). We reviewed the results of prebronchoscopy and postbronchoscopy sputum specimens, bronchial washings, brushings, and transbronchial biopsy to determine the yield from each specimen in patients with M. tuberculosis. The bronchial washings provided positive cultures in 24 of 25 and were exclusively positive in 10 of 25 (40%). We also reviewed the clinical presentation, chest roentgenogram, bronchoscopy findings, and culture data for the 87 patients with MOTT isolated. The isolation of MOTT from bronchoscopy specimens increased throughout the study, most notably with the introduction of a rapid radiometric method (the Bactec system) for the recovery of mycobacteria to our laboratory in June 1983. Active disease could be established in only 13 of 87 cases (15%). Our findings confirm the sensitivity of Bactec in the isolation of MOTT from bronchoscopic specimens. The Bactec system, on the other hand, does not differentiate saprophytic colonization from clinical disease. To avoid expensive, time-consuming biochemical identification necessary to evaluate these MOTT isolates, careful selection of patients prior to obtaining mycobacterial cultures during FB is a critical factor. PMID- 3087252 TI - The inhibition of sulfur dioxide-induced bronchoconstriction in asthmatic subjects by cromolyn is dose dependent. AB - To determine whether the inhibitory effect of cromolyn on sulfur dioxide-induced bronchoconstriction is dose dependent, we compared the effects of treatment with 200 mg of cromolyn, with 20 mg of cromolyn, and with placebo on the rise in specific airway resistance provoked by inhalation of serially increasing concentrations of sulfur dioxide (0.25 to 8.0 ppm) in 10 asthmatic subjects. The geometric mean concentration of sulfur dioxide needed to cause an increase in SRaw of 8 L X cm H2O/L/s was significantly greater after 200 mg of cromolyn (1.98 ppm) than after 20 mg of cromolyn (0.94 ppm), which was in turn significantly greater than after placebo (0.35 ppm). We then examined whether the greater protection afforded by 200 mg of cromolyn was due to direct inhibition of smooth muscle contraction. We measured the bronchomotor response to the inhalation of serially increasing concentrations of methacholine aerosol (0.06 to 2.0 mg/ml) in 7 asthmatic subjects. Again, each subject was treated on 3 separate days with 200 mg of cromolyn, with 20 mg of cromolyn, and with placebo. We found that methacholine responsiveness was not decreased by either dose of cromolyn. We conclude that cromolyn inhibits sulfur dioxide-induced bronchoconstriction in a dose-dependent manner and that it does not directly inhibit smooth muscle responsiveness. PMID- 3087253 TI - L-thyroxine dosage: a reevaluation of therapy with contemporary preparations. AB - Traditional L-thyroxine dosing formulas may overestimate the thyroid hormone requirement in patients treated with contemporary L-thyroxine preparations. We did clinical and laboratory assessments of 41 patients treated in successive periods with Levothroid (Armour Pharmaceuticals, Kankakee, Illinois) and Synthroid (Flint Division, Travenol Laboratories, Morton Grove, Illinois), obtaining 87 sets of data. Clinical subgroups were defined on the basis of the thyrotrophin response to thyrotrophin-releasing hormone. Normal responses were seen in 9 of 14 (64%) patients taking 100 micrograms/d and were associated with an average replacement dosage of 127 micrograms/d (1.7 micrograms/kg body weight). Nine of twenty-eight (32%) serum thyroxine values in the "physiologically replaced" group were elevated. Forty-three of fifty-four (80%) patients ingesting 125 micrograms or more had blunted responses (thyroxine "overreplaced"), averaging a daily dosage of 154 micrograms (2.14 micrograms/kg X d). No significant difference was found between Levothroid and Synthroid in predicting clinical group assignment. Guidelines for currently available L thyroxine preparations should be revised and the recommended dosage reduced. PMID- 3087255 TI - Buccal nitroglycerin tablets in heart failure. PMID- 3087254 TI - New modes of insulin administration: do they have a role in clinical diabetes? PMID- 3087256 TI - Alpha-difluoromethylornithine infusion and cardiac arrest. PMID- 3087258 TI - [Thyrotropic function in patients with a hypothalamic or pituitary tumor. Possibility of the secretion of a TSH with reduced biological activity]. AB - Thyrotropic function was studied in 100 patients with hypothalamic or pituitary tumours before treatment. Eighteen patients with thyroid deficiency showed no signs of primary hypothyroidism. This was also showed in 4 other hypothyroid patients who had pituitary tumours studied later on. Only 4 of these 22 patients had TSH deficiency. The other 18 had normal or high plasma TSH levels, and the TSH response to TRH was normal but often delayed and/or prolonged. This pattern, suggestive of secretion of TSH with reduced biological activity, might however be due to other factors. Tumoral invasion of the hypothalamus, present in these 18 cases, could reduce secretion of TRH and dopamine. Hypothyroidism would then be secondary to TRH deficiency if TRH is considered to have a direct thyroid stimulating action, and, like dopamine deficiency, could contribute to maintaining normal or high TSH secretion. PMID- 3087257 TI - [Amyloid pseudotumor disclosing non-secretory myeloma. Ultrastructural demonstration of the role of histiocytes in intratumoral amyloidogenesis]. AB - A 69 year old woman presented initially with an amyloid tumour of the rib. Six months later, she developed a plasma cell tumour of the left acromion diagnosed as an IgG kappa myeloma. Electron microscopy of the initial costal lesion and the plasma cell tumour showed a close resemblance between the dystrophic plasmacytes, which had no morphological evidence of intracytoplasmic amyloid fibrils, and the histiocytes, many of which contained these fibrils and were probable sites of amyloid secretion. This suggests that the costal amyloid tumour was probably the result of transformation of a previous plasma cell tumour, and that intra tumoural amyloid deposits have the same origin as the systemic amyloidosis observed in cases of multiple myeloma, i.e. the histiocyte. PMID- 3087259 TI - Streptococcus faecalis orbital cellulitis. AB - A case of orbital cellulitis in which the causative organism was Streptococcus faecalis--the first such case to the authors' knowledge--is reported. Although Hemophilus influenzae and pneumococci are most frequently encountered in orbital cellulitis, this case shows that Streptococcus faecalis may also be responsible. Prompt identification of the bacteria is urged. PMID- 3087260 TI - Rheological properties of middle ear effusions from children with otitis media with effusion. AB - Freshly harvested middle ear effusions (MEE) were collected from children with otitis media with effusion. Both elasticity (G') and viscosity (eta') of the MEE were determined by an oscillating sphere magnetic rheometer and compared with transportability of the MEE on mucus-depleted frog palates. A maximum value of transport was obtained at G' of about 20 dyne/cm2 (at 1 Hz), and below this value there was a significant positive correlation between the transport rate and log G'. Above 20 dyne/cm2, the negative correlation between the transport rate and log G' was significant. This shows there is a sharp increase in transport with increase in G' up to 20 dyne/cm2, and at the higher value of G' there is a slow decrease in transport with increasing G'. A similar significant correlation between the transport rate and log eta' was observed. PMID- 3087261 TI - Significance of kallikrein-kinin system in otitis media with effusion. AB - Significance of the kallikrein-kinin system in the pathogenesis of otitis media with effusion (OME) was evaluated by prekallikrein level, kallikrein activity, and concentration of high molecular weight (HMW) kininogen in 45 middle ear effusions (MEEs, 38 serous and seven mucoid). All MEEs had varying prekallikrein levels (73.1 +/- 127.5 relative fluoro units [RFU]), and the mean value in serous effusions (82.2 RFU) was much higher than that in mucoid effusions (23.0 RFU). Hydrolytic activity of kallikrein in serous effusions was 18.0 +/- 27.9 RFU, and was significantly higher than that in mucoid effusions (8.0 +/- 4.2 RFU, p less than 0.05). Concentration of HMW kininogen in serous effusions was 51.2 +/- 72.77% of plasma value, but it could not be detected in any mucoid effusions. Analysis of protein composition by polyacrylamide gel electrophoresis indicates that plasma protein that has leaked into the middle ear is a major component of MEEs. The kallikrein-kinin system would be active in serous effusions, and liberated bradykinin enhances vascular permeability in the middle ear mucosa, leading to profuse plasma leakage, which characterizes the component of serous effusions. On the other hand, this system would almost be consumed in mucoid effusions. PMID- 3087262 TI - Lysosomal thiol proteases in middle ear effusions. AB - Hydrolytic activity of lysosomal cathepsins B and H, and trypsin-like proteases in 115 middle ear effusions (MEEs, 40 serous and 75 mucoid) from chronic otitis media with effusion (OME) patients was measured and compared to that in plasma. The activity of both cathepsins in MEEs was significantly higher than that in plasma (p less than 0.01), and cathepsin B activity in mucoid MEEs was also significantly higher than that in serous MEEs (p less than 0.01). The activity of trypsin-like proteases was very weak in both MEEs and plasma. Profiles of various inhibitors indicated the qualitative difference of proteolytic enzymes between MEEs and plasma. Mucoid MEEs had significantly higher activity of thiol proteases than serous ones (p less than 0.01). Cathepsin B-like lysosomal thiol proteases, derived mainly from macrophages, could become a major proteolytic factor to perpetuate and amplify the inflammatory reaction of chronic OME. PMID- 3087263 TI - [Fabry's disease and annular granuloma]. PMID- 3087264 TI - Selenium and experimental cancer. PMID- 3087265 TI - Radioimmunoassay for human thyroxine-binding prealbumin. AB - A radioimmunoassay (RIA) for human thyroxine-binding prealbumin (PA) is described. It employs highly purified PA, anti-human PA serum at 1:30,000 final dilution, normal bovine serum as a carrier, and polyethyleneglycol to precipitate the immune complexes. This assay is extremely sensitive (limit of detection less than 0.2 micrograms per dL or less than 3.6 X 10(-15) moles per tube), accurate (recovery = 98.7 +/- 9 percent, mean +/- S.D.) and reproducible (intra- and inter assay coefficients of variation = 3.6 to 6.3 percent and 7.2 to 9.5 percent, respectively). There was a highly significant correlation when the RIA was compared with radical immunodiffusion or with PA maximal binding capacity for thyroxine (r = 0.944 and r = 0.724, respectively, p less than 0.001). Concentration of PA in sera from normal subjects (age range = 20 to 88 years) averaged 27.7 +/- 0.5 mg per dL (mean +/- S.E.M.), with significantly higher values in males than in females in all age groups with the exception of the older subjects (20 to 50 years: males = 26.5 to 37 mg per dL; females = 23.1 to 33.8 mg per dL). Levels of PA progressively declined after the fifth decade of life. Pregnancy, hyperthyroidism, chronic liver diseases, cystic fibrosis, cancer and other non-thyroidal illnesses were associated with decreased levels of serum PA. Untreated hypothyroidism and chronic renal diseases showed widely scattered values of PA. Inherited thyroxine-binding globulin (TBG) abnormalities and bisalbuminemia had no apparent effect on concentrations of serum PA. PMID- 3087266 TI - Appearance of light chain disease in serum electrophoresis. Report of 11 cases. AB - Over a five year period, 13 cases of light chain disease were identified. Ten patients had abnormalities noted on serum immunoelectrophoresis with anti-whole human antiserum. Eight of these ten patients had a distinctive rainbow-like arc between the IgG and transferrin arcs, and two had splitting of the IgG arc. These patterns may be seen in the presence of free light chains; their recognition should lead to further studies with appropriate antisera. PMID- 3087267 TI - An improved measurement of progesterone in saliva and clinical applications. AB - Measurement of progesterone in saliva offers several advantages when compared to assays of serum progesterone, especially when ovarian activity is being assessed. Most published methods for the determination of progesterone in saliva are based on assays developed in research centers, which employ "in-house" reagents that are critically dependent on supplies of highly selected antisera. In this report, the adaptation of a readily available commercial progesterone "kit", the Pantex Immunodirect Progesterone (125I) is described for the measurement of salivary progesterone. A single extraction step was added, however, to improve assay performance and to ensure that total salivary progesterone was measured. PMID- 3087268 TI - [Value of radiotherapy in the treatment of prostatic cancers in the initial stages. Apropos of 111 cases]. AB - The authors report on their experience with high energy radiation therapy in early-stage (I/II) carcinomas of the prostate. Among 191 cases of biopsy-proved carcinomas of the prostate, there were 111 stage I and II tumors, including 83 T1, T2 intracapsular tumors. 78 of the 111 patients received curative radiation therapy. Delivered doses did not exceed 65 to 70 grays to the prostate and 50 grays to the pelvis. High energy radiation was used. Extension of the lesions was determined using lymphography, abdominal and pelvic CT, and surgical removal of lymph nodes. Among the 78 irradiated patients, success rates at five years were 65% for the 52 T1-T2 tumors and 38% for the 26 T3 N0 tumors. Selection of patients, technical conditions and long term results are discussed, as well as the problems met in determining the stage of the tumor accurately. High energy radiation therapy can control localized carcinomas with a satisfactory quality of survival. PMID- 3087269 TI - [Treatment of advanced cancer of the prostate with an analog of LHRH, buserelin]. AB - Patients with metastatic prostatic cancer were treated by means of an LHRH agonist, Buserelin, by nasal administration. The serum testosterone levels were permanently decreased to castration levels in all patients. The objective response rate (CR + PR) was 50%. PMID- 3087270 TI - Successful treatment with tocainide of recessive generalized congenital myotonia. AB - A patient with recessive generalized congenital myotonia and severe, disabling weakness underwent various forms of treatment while being monitored electrophysiologically. Phenytoin, verapamil, and acetazolamide were ineffective, but tocainide yielded good results. Improvement was dose-dependent, and was limited by irritability and action tremor when the patient was taking 1,600 mg per day. PMID- 3087271 TI - Potential animal models for senile dementia of Alzheimer's type, with emphasis on AF64A-induced cholinotoxicity. AB - In this review we have described and critiqued several commonly used proposed animal models for SDAT. In particular, we have focussed on the AF64A-treated animal. Major pertinent neurochemical and behavioral data obtained so far with AF64A have been presented, and these effects have been compared with neurochemical and behavioral changes in the SDAT patient. We have commented on the possible mechanism(s) of action of AF64A in vivo, and have also presented some observations and speculations concerning the selectivity of action of AF64A as a specific presynaptic cholinotoxin. Much work has yet to be done with all the available animal models, including the AF64A-treated animal, before one could definitively state which one is the ideal model for SDAT. Data obtained to date with the AF64A-treated animal are nevertheless most encouraging. Despite some caveats, AF64A is a valuable neurochemical tool with which one can induce a persistent cholinergic deficiency of presynaptic origin. As with all new tools, however, one must always exercise due care to use it properly, and interpret the results obtained following its administration with caution. PMID- 3087272 TI - [Fusion of Bacillus subtilis and Bacillus licheniformis protoplasts. The mapping of the mutations leading to the supersynthesis of riboflavin in interspecies hybrids]. AB - As a result of fusion of the protoplasts of B. subtilis and B. licheniformis the majority of the prototrophic hybrids, as well as the auxotrophs with the Thi-Hom phenotype or the Thi-phenotype acquired capacity for over-production of riboflavin lacking in the initial parent strains. When grown on the minimal Spizizen medium with aeration at 37 degrees C the auxotrophic recombinants accumulated 10-60 micrograms/ml of riboflavin for 2 days, while the prototrophic recombinants accumulated up to 90 micrograms/ml of riboflavin. The respective figures for their cultivation in the sucrose fermentation medium were 100-330 and 600 micrograms/ml. For mapping 3 random variants of them with different phenotypes, i.e. SL-7 (prototroph), SL-15 Thi-and SL-52 Thi-Hom-were used. Localization of the mutation on the chromosome of B. subtilis was based on transformation experiments with three marker crossing, where hybrid strains SL-7, S1-15 and SL-52 were used as the DNA donor and strain lys-rib-of B. subtilis was used as the recipient. The analysis showed that the required mutation designated as R1 was localized on the chromosome of B. subtilis in the regulatory region rib0 of the riboflavin operon. PMID- 3087273 TI - [Fluorescent pseudomonads. Their antibiotic sensitivity, clinical significance and problems of identification]. PMID- 3087274 TI - In vitro evaluation of A-56619 (difloxacin) and A-56620: new aryl fluoroquinolones. AB - The in vitro antibacterial potencies of A-56619 and A-56620, two new aryl fluoroquinolones, were compared with the potency of norfloxacin against a broad spectrum of organisms. Cefotaxime, aztreonam, piperacillin, imipenem, penicillin, and gentamicin were also tested for reference purposes. The MICs required to inhibit at least 90% of the strains tested ranged from 0.25 to 4 micrograms/ml for A-56619 and from 0.06 to 0.5 microgram/ml for A-56620 for members of the Enterobacteriaceae. A-56619 was generally twofold less potent and A-56620 was twofold more potent than norfloxacin against most aerobic gram-negative bacilli, including members of the Enterobacteriaceae and Pseudomonas aeruginosa. Against indole-positive Proteus, Morganella, Providencia rettgeri, and Serratia strains, A-56619 was at least 8- to 16-fold less potent than norfloxacin. A-56619 and A 56620 were four- to eightfold more potent than norfloxacin against Staphylococcus aureus and equally potent to fourfold more potent against Streptococcus species, Haemophilus influenzae, and Neisseria gonorrhoeae. The MICs of A-56619 and A 56620 were only slightly affected by increased inoculum size or by the addition of various cations at physiologic concentrations. A-56619 was three- to fivefold less active at pH 8.0 than at pH 6.5 or 7.2. A-56620 was twofold less active at pH 6.5 than at pH 8.0 or 7.2 against members of the Enterobacteriaceae and Pseudomonas aeruginosa; similar pH variations did not affect A-56620 activity against gram-positive cocci. The potencies of A-56619, A-56620, and norfloxacin were less in urine than in Mueller-Hinton broth; however, this effect was more pronounced with norfloxacin. Human serum at a concentration of 50% caused a 4- to 64- fold decrease in the potency of A-56619 and an average 4-fold decrease in the potency of A-56620, compared with no effect on the potency of norfloxacin. A 56619, A-56620, and norfloxacin were bactericidal and, at four times the MIC, reduced the viable cell counts of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa by approximately 99.9% within 2 h. A-56619, A-56620, and norfloxacin showed no significant synergistic activity and no antagonism when they were aminoglycoside or beta-lactam antimicrobial agents. PMID- 3087275 TI - The effect of antimicrobial agents on fecal flora of children. AB - Influences of antibiotics on the fecal flora in children were studied for oral ampicillin, penicillin V, erythromycin, cefaclor, and gentamicin and for intravenous ampicillin, methicillin, cefpiramide, and ceftazidime. All antibiotics affected the normal flora, although the quality and quantity of the changes were variable. No substantial differences were noted between the oral and intravenous use of ampicillin with regard to its effect on the flora. Three penicillins, ampicillin, penicillin V, and methicillin, caused remarkable changes. The characteristic pattern observed was the considerable suppression of Bifidobacterium, Streptococcus, and Lactobacillus species. Although enterobacteria did not significantly change in number, Klebsiella spp. frequently replaced Escherichia coli. In patients given erythromycin and cefaclor, the reduction in the number of Bifidobacterium spp. was 1 log10 and that of members of the family Enterobacteriaceae was 3 log10. Gentamicin administered orally caused a drastic change, including a remarkable decline of E. coli to less than 2 log10/g of feces. Cefpiramide, a parenteral expanded-spectrum cephalosporin, suppressed normal flora so markedly that almost all species of organisms were eradicated, and the active growth of yeasts was promoted (2.6 log10 increase). Ceftazidime caused similar changes as cefpiramide, but the changes were less extensive. Yeasts increased after treatment with most antibiotic groups. This increase was particularly prominent in patients given oral penicillins and expanded-spectrum cephalosporins. PMID- 3087276 TI - Bactericidal activity and killing rate of serum from volunteers receiving pefloxacin alone or in combination with amikacin. AB - Serum bactericidal activities (SBAs) were studied after intravenous administration of pefloxacin (8 mg/kg) and amikacin (7.5 mg/kg) alone or in combination to 15 human volunteers. About 10 strains each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus were tested. The serum levels of pefloxacin were measured microbiologically by using E. coli KP 1976-712 as the test organism at 0, 30, 60, 120, and 720 min after infusion; at 0, 30, 60, and 720 min these levels were 7 +/- 1.4, 5 +/- 0.8, 4.5 +/- 0.7, and 2.1 +/- 0.6 mg/liter (mean +/- standard deviation), respectively, with a terminal half-life of 10 h. The serum levels of pefloxacin in the presence of amikacin were measured similarly; 1% sodium polyanethol sulfonate was added to the agar to inactivate amikacin. Treatment with pefloxacin alone resulted in high SBAs against E. coli, K. pneumoniae strains susceptible to cephalothin, and Staphylococcus aureus at the peak concentration; 81 to 100% of the sera had SBAs of greater than or equal to 1:8. However, treatment with pefloxacin alone resulted in low SBAs against K. pneumoniae strains resistant to cephalothin and P. aeruginosa; only 34% of the sera had SBAs of greater than or equal to 1:8. At trough concentrations the percentages of sera with SBAs greater than or equal to 1:8 were 75 to 83% (E. coli), 9 to 27% (K. pneumoniae), 0% (P. aeruginosa), and 10% (S. aureus). The combination of pefloxacin plus amikacin was most often additive; the peak activity was due to amikacin, and the trough activity was due to pefloxacin. Occasionally antagonism occurred with P. aeruginosa, K. pneumoniae, and S. aureus strains. These observations were confirmed by the killing curves in pooled serum obtained at peak and trough levels. Regrowth was observed for seven strains of P. aeruginosa treated with pefloxacin alone; amikacin seemed to prevent this phenomenon. PMID- 3087278 TI - Enhanced toxicity of copper for Streptococcus mutans under anaerobic conditions. AB - Copper inhibition of 11 strains (serotypes a through g) of Streptococcus mutans was increased by anaerobic incubation. Anaerobic toxicity was reversed by cuprous, but not by cupric, chelators. Susceptibility to aerobic copper inhibition was related to serotype; serotypes c, e, and f (biotype I) were most sensitive. PMID- 3087277 TI - In vitro and in vivo studies of imipenem-cilastatin alone and in combination with gentamicin against Listeria monocytogenes. AB - Imipenem was evaluated for its in vitro and in vivo activities alone and in combination with gentamicin against a clinical isolate of Listeria monocytogenes, and the results were compared with the activities of ampicillin with and without gentamicin. In vitro, the MBC of imipenem was fourfold less than that of ampicillin. Checkerboard determinations of the MBCs exhibited a synergistic response for imipenem-gentamicin but an indifferent response for ampicillin gentamicin. In vivo studies with experimental bacteremia and meningitis due to L. monocytogenes in newborn rats revealed that both imipenem-cilastatin and ampicillin at a dose of 50 mg/kg produced excellent bactericidal titers in serum. Overall mortality rates were not significantly different among four groups of animals receiving imipenem-cilastatin, imipenem-cilastatin-gentamicin, ampicillin or ampicillin-gentamicin. However, imipenem-cilastatin alone or in combination with gentamicin was significantly less effective than ampicillin-gentamicin, as judged by the rapidity of clearance of bacteria from blood, liver, and spleen. These findings suggest that imipenem-cilastatin and imipenem-cilastatin gentamicin may not be suitable alternatives for the treatment of listeriosis. PMID- 3087279 TI - In vitro activities of selected new and long-acting cephalosporins against Pasteurella multocida. AB - The activities of six agents commonly used in treating infections of the skin and soft tissues and the action of selected cephalosporins against 15 isolates of Pasteurella multocida were assessed by a macro-broth dilution method. Broad spectrum cephalosporins, including ceftriaxone and cefixime, had excellent in vitro activities (MIC less than or equal to 0.098) against the isolates tested. PMID- 3087280 TI - Comparative in vitro antimicrobial activity of carumonam, a new monocyclic beta lactam. AB - The antimicrobial activity of carumonam (formerly RO-17-2301), a monocyclic beta lactam antibiotic, was compared with those of aztreonam, cefotaxime, cefoperazone, ceftazidime, piperacillin, and gentamicin against 455 bacterial isolates. Carumonam did not possess activity against gram-positive cocci and was generally comparable to aztreonam and ceftazidime for most gram-negative bacilli. However, carumonam was the most active beta-lactam against gentamicin-resistant Pseudomonas aeruginosa strains (90% MIC, 8 micrograms/ml). PMID- 3087281 TI - In vitro activity of BRL 36650, a new penicillin. AB - Compared with four beta-lactam antibiotics and amikacin, BRL 36650 and BMY-28142 were the most active against 509 Enterobacteriaceae, including cefotaxime resistant isolates and resistant laboratory mutants. BRL 36650 was more active than aztreonam, ceftazidime, and BMY-28142 against Acinetobacter spp., Pseudomonas aeruginosa, and other Pseudomonas spp.; all strains were inhibited by 2 micrograms/ml or less. PMID- 3087282 TI - Comparative study of serum bactericidal activity of cefotaxime alone or in combination with tobramycin. AB - The objectives of this study were to investigate the bactericidal activity in serum of cefotaxime alone or in combination with tobramycin against clinical strains and to determine the influence of tobramycin on the pharmacokinetics of cefotaxime. The peak bactericidal activity in serum of cefotaxime alone against Klebsiella oxytoca, Enterobacter aerogenes, Serratia marcescens, Pseudomonas cepacia, and Listeria monocytogenes varied between 1:4 and 1:256. Bactericidal activity could still be detected at 6 h against K. oxytoca and L. monocytogenes. The addition of tobramycin increased the bactericidal activity of cefotaxime against E. aerogenes from 1:16 to 1:128 (P less than 0.01). Cefotaxime recovery from urine was significantly decreased when tobramycin was added. Our data are comparable with those of other investigators who have shown a limited increase in the bactericidal activity of cefotaxime when aminoglycosides are added. PMID- 3087284 TI - Characterization of an antibiotic produced by a strain of Pseudomonas fluorescens inhibitory to Gaeumannomyces graminis var. tritici and Pythium spp. AB - The production, isolation, and characterization of an antibiotic substance from cultures of Pseudomonas fluorescens 2-79 (NRRL B-15132) is described. P. fluorescens 2-79 originally was isolated from the roots of wheat and is suppressive to the wheat root disease take-all caused by Gaeumannomyces graminis var. tritici. The antibiotic was isolated from potato glucose broth cultures of strain 2-79 by solvent extraction. It was purified by silica gel column chromatography and was a greenish yellow, needle-shaped crystal with a melting point of 242 degrees C (decomposition). It was soluble in methylene chloride, chloroform, acetone, 2 N sodium hydroxide, and 2 N hydrochloric acid and was insoluble in water, methanol, ethyl acetate, tetrahydrofuran, diethyl ether, carbon tetrachloride, hexane, and petroleum ether. On the basis of UV, infrared, 1H-nuclear magnetic resonance, 13C-nuclear magnetic resonance, mass spectral analysis, and elemental analysis, the structure of the antibiotic is proposed to be a dimer of phenazine carboxylic acid. Lithium aluminum hydride reduction of the antibiotic yielded hydroxymethyl phenazine as a major product which retained most of the biological characteristics of the parent molecule. There were no toxic symptoms when mice received this antibiotic by oral doses up to 464 mg/kg. The antibiotic showed excellent activity against several species of fungi, including the wheat pathogens Gaeumannomyces graminis var. tritici, Rhizoctonia solani, and Pythium aristosporum; and it may have a role in suppression of take all in vivo by strain 2-79. PMID- 3087283 TI - Cloning and expression in Escherichia coli of a gene encoding nonenzymatic chloramphenicol resistance from Pseudomonas aeruginosa. AB - High-level chloramphenicol resistance in Pseudomonas aeruginosa may be due to enzymatic inactivation, ribosomal mutation, or a permeability barrier. We investigated the nonenzymatic resistance mechanism encoded by Tn1696, a transposon found in P. aeruginosa. A 1-megadalton DNA fragment from Tn1696 was cloned which mediated expression of chloramphenicol resistance in Escherichia coli. Comparison of the effects of chloramphenicol on in vitro translation revealed no difference between the susceptible recipient strain and the resistant transformant containing the cloned gene. The rate of chloramphenicol uptake was slower in the resistant strain, suggesting a permeability barrier to the antibiotic. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membranes demonstrated the absence of a 50,000-dalton protein in the resistant strain. DNA homology was evident between Tn1696 and chloramphenicol-resistant isolates of Haemophilus influenzae possessing altered outer membrane permeability. We conclude that chloramphenicol resistance encoded by Tn1696 is due to a permeability barrier and hypothesize that the gene from P. aeruginosa may share a common ancestral origin with these genes from other gram negative organisms. PMID- 3087285 TI - Properties of a novel carbenicillin-hydrolyzing beta-lactamase (CARB-4) specified by an IncP-2 plasmid from Pseudomonas aeruginosa. AB - CARB-4, a novel carbenicillin-hydrolyzing beta-lactamase with an isoelectric point of 4.3, was discovered in a strain of Pseudomonas aeruginosa from France. It was determined by a multiresistant transmissible plasmid belonging to the P-2 incompatibility group. PMID- 3087286 TI - Cost-effective retractors for laser surgery. PMID- 3087287 TI - Induction of mouse epidermal ornithine decarboxylase by the tumor promoter 12-O tetradecanoylphorbol-13-acetate: dependence on calcium availability. AB - The role of calcium in epidermal ornithine decarboxylase (ODC) induction by 12-O tetradecanoylphorbol-13-acetate (TPA) was determined in adult mouse skin pieces incubated in serum-free minimal essential medium (MEM). Addition of TPA to skin pieces incubated in serum-free MEM, which contains 1.82 mM Ca2+ and 0.83 mM Mg2+, resulted in about a 200-fold increase in epidermal ODC activity at about 8 h after TPA treatment. TPA failed to induce epidermal ODC in skin pieces incubated in calcium-free medium. Similarly, chelation of extracellular calcium by ethyleneglycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA) prevented ODC induction by TPA, which could be resumed upon calcium restoration in the medium. Furthermore, calcium ionophore A23187, which facilitates efflux of Ca2+ across cellular membranes, induced ODC activity in incubated skin pieces. Epidermal ODC activity increased by TPA appears to be the result of an increase in both the amount of ODC protein and the level of hybridizable ODC messenger. Inhibition of the induction of ODC activity by EGTA was the result of the inhibition of the amount of active ODC protein and the level of ODC mRNA. PMID- 3087288 TI - Evidence for induction of hepatic microsomal cytochrome P-450 by cimetidine: binding and kinetic studies. AB - The interaction of cimetidine with liver microsomes has been examined by spectral and equilibrium partition studies. First, difference spectroscopy has been used to evaluate the proportion of cytochrome P-450 in rat liver microsomes that exhibits an affinity for cimetidine in the pharmacologically relevant, low micromolar range of drug concentration. The value of 0.45 so obtained has confirmed that a substantial proportion of rat liver cytochrome P-450 has a high binding affinity for this drug. Second, a study of the binding of cimetidine to human liver microsomes by difference spectroscopy and partition equilibrium has detected a similar interaction, thus providing direct support for the postulate that the clinically observed impairment of oxidative drug metabolism may be due in part to inhibition of cytochrome P-450 monooxygenase by cimetidine. Hepatic microsomes from cimetidine-pretreated rats have been shown to exhibit elevated cytochrome P-450 specific content but a decreased proportion of sites with high affinity for the drug; this finding has been shown not to be the consequence of cimetidine-mediated, time-dependent, irreversible monooxygenase inhibition. Although cimetidine pretreatment caused enhanced specific activity of 7 ethoxyresorufin O-dealkylation, the specific activities for O-dealkylation of 7 ethoxycoumarin and 4-nitroanisole were decreased, as were those for the N dealkylation of morphine, ethylmorphine, aminopyrine, and dimethylnitrosamine. Since cimetidine pretreatment was shown to cause no change in the Michaelis constants for oxidation of morphine or 7-ethoxyresorufin, it is argued that these results provide strong presumptive evidence for changes in the relative abundance of isoenzymes catalyzing these various oxidations. Thus, a dual role of cimetidine, acting both as inhibitor and inducer of the cytochrome P-450 system, is proposed to account for the impaired oxidative metabolism of some drugs that occurs during coadministration with this H2-receptor antagonist. PMID- 3087289 TI - Isolation and characterization of buckwheat (Fagopyrum esculentum M.) chalcone synthase and its polyclonal antibodies. AB - Chalcone synthase was isolated from illuminated buckwheat (Fagopyrum esculentum M.) hypocotyls and purified to electrophoretic homogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis using (NH)4SO4 fractionation, gel filtration on AcA 44, ion exchange chromatography on DEAE-Bio-Gel, and HPLC on hydroxylapatite. The properties of the enzyme were pH optimum, 8.0; Mr approximately 83,000 +/- 1000; Mr subunit, approximately 41,500 +/- 500; isoelectric point, pH 5.2; Km, 1 X 10(-6)M for malonyl-CoA, and 0.6 X 10(-6) M for p-coumaryl-CoA. Buckwheat chalcone synthase used p-coumaryl-CoA as substrate and also utilized caffeyl-CoA and ferulyl-CoA at 20 and 80%, respectively, of the rate of p-coumaryl-CoA in the chalcone synthase reaction. Antibodies against the buckwheat chalcone synthase were developed in a New Zealand white rabbit and characterized for specificity by enzyme-linked immunosorbent assay, Ouchterlony double immunodiffusion, and Western blotting. PMID- 3087290 TI - Comparison of kinetic and molecular properties of two forms of amygdalin hydrolase from black cherry (Prunus serotina Ehrh.) seeds. AB - Two forms of the beta-glucosidase amygdalin hydrolase (AH I and II), which catalyze the hydrolysis of (R)-amygdalin to (R)-prunasin and D-glucose, have been purified over 200-fold from mature black cherry (Prunus serotina Ehrh.) seeds. These proteins showed very similar molecular and kinetic properties but could be resolved by chromatofocusing and isoelectric focusing. AH I and II were monomeric (Mr 60,000) and had isoelectric points of 6.6 and 6.5, respectively. Their glycoprotein character was indicated by positive periodic acid-Schiff staining and by their binding to concanavalin A-Sepharose 4B with subsequent elution by alpha-Me-D-glucoside. Of the natural glycosidic substrates tested, both enzymes showed a pronounced preference for the endogenous cyanogenic disaccharide (R) amygdalin. They also hydrolyzed at the same active site the synthetic substrates p-nitrophenyl-beta-D-glucoside and 4-methylumbelliferyl-beta-D-glucoside but were inactive towards (R)-prunasin, p-nitrophenyl-alpha-D-glucoside, and 4 methylumbelliferyl-alpha-D-glucoside. Maximum hydrolytic activity was shown in citrate-phosphate buffer in the pH range 4.5-5.0. AH I and II were inhibited competitively by the reaction product (R)-prunasin and noncompetitively (mixed type) by delta-gluconolactone and castanospermine. PMID- 3087292 TI - [Anosmia or hyposmia after long-term oral administration of tegafur--improved anosmia]. AB - Seventeen patients who manifested anosmia or hyposmia after long-oral administration of Tegafur (FT-207) in postoperative chemotherapy for cancer were followed up. Anosmia improved in 9 of 17 patients (52.9%), and the recovery period was between 3 and 42 months after the manifestation, and between 1 and 35 months after discontinuation of FT-207. Rhinoscopy and radiography revealed no abnormal findings in the nasal septum, rima oflactoria, concha nasalis media, sinus ethmoidales, etc. As it took a long time to recover from these signs and symptoms, they were presumed to be due to reversible neurological anosmia or hyposmia. PMID- 3087291 TI - Glucosylceramide in the androgen-responsive kidney of the lizard Anolis carolinensis. AB - During the spring breeding season of the American chameleon, Anolis carolinensis, elevated levels of glucosylceramides which contain hydroxy fatty acids are produced in the kidneys of males but not females. Hyperproduction of this glycolipid is also induced by testosterone. The testosterone-induced hypertrophy of epithelial cells in the proximal tubules of the mouse kidney seems an analogous phenomenon and an elevated concentration of specific glycolipids in the male mouse kidney has been previously demonstrated. Thus the formation of renal glycolipids in response to testosterone may be a widespread feature in vertebrates. PMID- 3087293 TI - [A randomized controlled trial of surgical adjuvant therapy with mitomycin C, 5 fluorouracil and OK-432 in patients with gastric cancer]. AB - The effect of postoperative immunochemotherapy with mitomycin C (MMC), 5 fluorouracil (5-FU) and OK-432 was evaluated as an adjuvant therapy after curative resection for gastric cancer. Immediately after surgery, patients were randomly allocated to the following three treatments: (A) chemotherapy with MMC and 5-FU (32 cases); (B) chemoimmunotherapy with MMC, 5-FU and OK-432 (33 cases); and (C) surgery alone as control (34 cases). There were no significant differences in the background factors influencing survival time among the groups, and there was no dose-distribution of chemotherapeutic agents between groups A and B. While the differences were not statistically significant, the survival rate and disease-free interval of group B were better than those of groups A or C. Side effects such as gastroenteric disorder, leukopenia (less than 3,000/mm3), thrombocytopenia (less than 7 X 10(4)/mm3) and increase of serum transaminase level (GPT greater than or equal to 100 units) were less frequently observed in group B than in group A. The results of the present study seemed to indicate that chemoimmunotherapy with OK-432 may be effective for surgical adjuvant therapy. PMID- 3087295 TI - Adverse reactions to bovine collagen implants. Additional evidence for immune response gene control of collagen reactivity in humans. PMID- 3087294 TI - [Study on the concentration of FT-207 and 5-FU in serum and tissues of bladder tumor and prostatic carcinoma]. AB - Serum and tissue concentrations of 5-FU and FT-207 were estimated in 26 patients with bladder tumor or prostatic carcinoma after administration of FT-207 suppositories. The 5-FU concentration in bladder tumor was higher than in normal mucosal bladder tissue. The 5-FU concentration of prostatic cancer was almost equal to that of normal prostatic tissue. Relatively higher concentrations of 5 FU were recognized in bladder tumor of a high stage than of a low stage. There were no differences of serum and tissue 5-FU concentration in bladder tumor between patients more than 65 years old and those under 65 years old. No side effects occurred in any case during suppository administration. PMID- 3087296 TI - Evaluation of adenosine deaminase activity and antibody to Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid and the radioactive bromide partition test for the early diagnosis of tuberculosis meningitis. AB - A number of different biochemical and serological tests have been described recently for the early and accurate diagnosis of tuberculous meningitis. None of these tests has yet gained widespread acceptance in clinical medicine or in microbiology laboratories. To investigate this problem we evaluated adenosine deaminase activity (ADA), an enzyme linked immunosorbent assay (ELISA) that detects antibody to antigen 5 of Mycobacterium tuberculosis, and the radioactive bromide partition test (BPT) in the cerebrospinal fluid (CSF). Cerebrospinal fluid specimens from children with tuberculous, pyogenic, and viral meningitis as well as from patients with pulmonary tuberculosis without meningitis and from controls with normal CSFs were included inn the study. In addition, we estimated ADAs in serum samples from selected children in these groups. The sensitivity and specificity of the three tests evaluated in the CSF were: ADA assay 73% and 71%; BPT 92% and 92%; and ELISA for antibody to antigen 5, 53% and 90%, 40% and 94%, and 27% and 100%, respectively, at tires of more than or equal to 1:20, 1:40, and 1:80. The serum ADA was lower (11.0 +/- 6.15 IU/l) in children with tuberculous meningitis when compared with those with pulmonary tuberculosis alone (25.8 +/- 20.9 IU/l). The BPT was found to be the most reliable test in the early differentiation of tuberculous from other causes of meningitis and remained abnormal for a period of up to five months after the beginning of treatment. Accordingly, we believe that the BPT should be used in conjunction with bacterial and fungal antigen detection systems for the initial differentiation of clinically suspicious tuberculous meningitis from Gram or culture negative cases, or both, of bacterial and fungal meningitis. PMID- 3087297 TI - Central venous catheterisation in very low birthweight infants. AB - Forty two premature babies (mean birth weight 980 g, mean gestation 27.6 weeks) had central venous lines inserted at a mean age of 10 days through the internal jugular vein because of poor peripheral venous access and for purposes of parenteral feeding and minimal handling. Eight babies died from complications of prematurity and four from septicaemia with a central line in situ, but the other 30 babies had lines in place for a mean of 20 days. A mean weight gain of 17.5 g/kg/day was recorded. Eight babies showed signs of infection at a mean of 22 days after insertion of the line. The other complications were thrombosis related to the catheter (three cases), embolisation (two), and hydrocephalus related to superior vena caval thrombosis (one). The policy of management is outlined, and the risks and benefits of the technique are analysed. PMID- 3087298 TI - Calcium and phosphate content of intravenous feeding regimens for very low birthweight infants. AB - Fifteen infants with birth weights below 1500 g, who required intravenous feeding from birth, were given one of two regimens differing only in their calcium and phosphate content. The duration of intravenous feeding varied from 26 to 75 days, and infants were studied after the age of 10 days when growth could be expected to have started. Five infants were given regimen A, which provided calcium and phosphate intakes of 0.55 and 0.44 mmol/kg/day, and 10 received regimen B, which provided intakes of 1.08 and 0.89 mmol/kg/day, respectively. Infants given regimen A had lower plasma and urine phosphate but similar urine calcium excretion to those given regimen B. Plasma calcium concentrations were higher in infants on regimen A than regimen B. In infants given regimen B plasma phosphate concentration was inversely related to weight gain, and urine phosphate and calcium concentrations were significantly correlated with urine sodium results. PMID- 3087299 TI - Cultured human cells can acquire resistance to the antiproliferative effect of sodium aurothiomalate. AB - Cultured human epithelial cells (HE), grown as monolayers, acquired resistance to otherwise lethal concentrations (300 mumol/l, culture medium) of sodium aurothiomalate during five months' exposure to stepwise increased concentrations of the drug. The resistance acquired was shown by exposure to drug concentrations ranging from 25 to 300 mumol/, resulting in 100% of the resistant cells (HeMyo) surviving compared with controls. Only 13% of the sensitive parent cells survived when exposed to 300 mumol/l for four days. The HeMyo cells were also resistant to the antiproliferative effects of equimolar concentrations of thiomalic acid without gold. The cytosolic gold concentration and the association of 199Au with cytosolic proteins after gel filtration were similar in both cell lines after sodium aurothiomalate exposure to the exponentially growing cells. No synthesis of gold binding proteins of metallothionein character was observed in the HEMyo cells. The concentration of free thiomalate in the sonicates and cytosols of the HeMyo cells was decreased to 25-30% of the concentration found in the HE cells. Comparison with previous data for the cytosolic concentration of total thiomalate in the HE cells suggests that most of the cytosolic thiomalate present was free thiomalate. We conclude that the cells can develop resistance to the antiproliferative effect of sodium aurothiomalate, and that the resistance may be due to their capacity to maintain low concentrations of free thiomalate in the sonicates and cytosols. The results support previous findings that sodium aurothiomalate appears to dissociate within cells. PMID- 3087300 TI - Budd-Chiari syndrome as the major thrombotic complication of systemic lupus erythematosus with the lupus anticoagulant. AB - A patient with systemic lupus erythematosus was first diagnosed after she had developed the Budd-Chiari syndrome. We believe that the Budd-Chiari syndrome was part of her tendency for thrombosis, induced by the presence of a lupus anticoagulant. The association between enhanced thrombosis and the lupus anticoagulant is discussed, and the need for prompt recognition and administration of anticoagulant therapy is emphasised. PMID- 3087301 TI - [Prevalence and antibiotic sensitivity of Neisseria gonorrhoeae infection in a rural area in Kivu, Zaire]. PMID- 3087302 TI - Enhancing detection of gonococcus in ejaculates of adult males using sperm dilution. AB - Specific cultures were used to detect growth of Neisseria Gonorrhoeae (NG) in 90 ejaculates of partners of childless marriages. Although no gonococcal growth was observed in undiluted semen, 9 out of 68 subjects with silent infection presented growth of NG in seminal plasma after dilution 1:2 with saline. It is concluded that semen dilution increases the chances of detection of NG in semen samples of asymptomatic gonococci carriers. PMID- 3087303 TI - [Health education in the early detection of prostatic diseases]. PMID- 3087304 TI - Studies on the hypothermic response of capsaicin and its analogue in mice. AB - Administration of capsaicin (CAP) and its related pungent, nonanoyl vanillylamide (NVA) produced significant dose-dependent hypothermic response in mice at an ambient temperature of 24 degrees C. CAP was approximately equieffective to NVA in producing hypothermia. After large doses, desensitization occurred to the hypothermic effects of both CAP and NVA. The hypothermia produced by CAP and NVA was prevented by a small dose of thyrotropin-releasing hormone (TRH) (0.25 nmol/animal) which by itself had little effect on body temperature. Histidyl proline diketopiperazine, a metabolite of TRH, was without effect on the hypothermic response of CAP and NVA. The result suggests that a TRH neuronal system in the brain may explain a part of the mechanism of CAP- and NVA-induced hypothermia in mice. PMID- 3087305 TI - Mode of cerebral vasodilating action of KC-404 in isolated canine basilar artery. AB - 3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (KC-404) caused a potent and concentration-dependent relaxation in isolated canine basilar artery precontracted with prostaglandin (PG) F2 alpha attended by EC50 of 7.6 X 10(-8) g/ml. The relaxing action of KC-404 was little affected by the removal of vascular endothelium, whereas it was significantly diminished by pretreatment with indomethacin (10(-5) M) or acetylsalicylic acid (ASA) (10(-3) M). In PGF2 alpha-contracted canine basilar artery, KC-404-induced relaxation was markedly reversed to contraction by the subsequent addition of indomethacin (10(-5) M), ASA (10(-3) M) and phenidone (10(-4) M) by about 80%, 75% and 111%, respectively, whereas it was little affected by nordihydroguaiaretic acid (NDGA) (10(-5) M). Similar results were obtained when dipyridamole was used as a relaxant but, in contrast, papaverine-induced relaxation was little affected by indomethacin. KC 404 as well as PGI2 showed less potent or no relaxation in both PGF2 alpha contracted rabbit aorta and KCl-contracted canine basilar artery as compared with PGF2 alpha-contracted canine basilar artery. In PGF2 alpha-contracted canine basilar artery, PGI2-induced relaxation was significantly augmented by pretreatment with KC-404 (10(-8) and 10(-7) g/ml). These results suggest that KC 404 might elicit cerebral vasorelaxation not dependent on vascular endothelium but remarkably dependent on a vasodilating cyclooxygenase metabolite, possibly PGI2. PMID- 3087306 TI - Effects of diazepam on pancreatic exocrine secretion in the dog. AB - The effects of diazepam on pancreatic exocrine secretion were investigated in the vascularly isolated and self-hemoperfused dog pancreas under constant perfusion pressure of 100 mmHg. Close-arterial injections (i.a.) of diazepam (0.3-3.0 mg) caused dose-dependent increases in the secretion of pancreatic juice and in the rate of perfusion blood flow. Protein and bicarbonate concentrations of the pancreatic juice stimulated by 3.0 mg of diazepam were significantly higher than those of the resting pancreatic juice. The secretory activity of 1.0 mg (i.a.) of diazepam was comparable to that of 0.05 units (i.a.) of secretin. These secretory and vascular responses to diazepam were not modified by pretreatments with atropine, sulpiride, cimetidine, theophylline and Ro 15-1788. These results suggest that large doses of diazepam act directly on both acinar and ductular cells of the pancreas and induce protein and bicarbonate secretions. PMID- 3087307 TI - Cefotaxime vs nafcillin and tobramycin for the treatment of serious infection. Comparative cost-effectiveness. AB - To evaluate the cost-effectiveness of cefotaxime sodium at a dosage of 12 g/day vs nafcillin sodium and tobramycin sulfate for the treatment of serious infection, the hospital and physician charges of patients enrolled in a prospective, randomized, clinical trial were analyzed. For 187 patients receiving therapy empirically, mean hospital charges for the interval in which the trial antibiotics were used were $3,550 +/- $1,740 for cefotaxime and $3,160 +/- $1,990 for nafcillin and tobramycin. After adjusting for cost-generating factors, charges for cefotaxime were greater than for nafcillin and tobramycin, but the difference was not significant. For 107 patients with clinically or bacteriologically documented infection, mean charges were $3,980 +/- $1,800 for cefotaxime and $4,170 +/- $1,780 for nafcillin and tobramycin. Adjusted charges did not differ. Incremental charges for cefotaxime per additional response were $1,630 in all patients and -$820 in patients with clinically or bacteriologically documented infections. PMID- 3087308 TI - Recurrent thrombosis and lupus anticoagulant in systemic lupus erythematosus. PMID- 3087309 TI - Is it appropriate for primary care physicians to perform skin biopsies? PMID- 3087311 TI - Long-term suppression of recurrent herpes labialis by low-dose oral acyclovir in an immunocompromised patient. AB - A patient with chronic lymphocytic leukemia and severe and frequently recurring herpes labialis received oral acyclovir for more than 18 months, during most of this period at a low dosage (400 mg/d). This regimen was fully successful in preventing recurrences, with no adverse effects. PMID- 3087310 TI - Effect of aminophylline on exercise performance in patients with irreversible airway obstruction. AB - Thirteen clinically stable male patients aged 63 +/- 3 years with irreversible airway disease were given aminophylline and placebo in a randomized crossover fashion on two consecutive days while receiving beta-agonists. During incremental exercise the maximal heart rate (139.0 +/- 22.1 vs 128.0 +/- 16.4 beats per minute) and minute ventilation (41.9 +/- 6.9 vs 38.1 +/- 8.2 L/min) were significantly higher and the arterial carbon dioxide pressure (34.6 +/- 5.0 vs 38.6 +/- 7.7 mm Hg) was significantly lower during aminophylline administration than during placebo administration. However, spirometric findings, maximal inspiratory pressures, maximal oxygen consumption, work rate, and arterial oxygen pressure were similar on both regimens. We concluded that the major effect of aminophylline is to increase ventilatory drive in patients with irreversible airway obstruction. Unless an objective change in spirometric data or exercise capacity can be documented, we believe that aminophylline therapy is not warranted in these patients. PMID- 3087312 TI - [Clinical, echocardiographic and evolutive aspects of right atrial thrombosis]. AB - The clinical and echocardiographic features of right atrial thrombi were examined in 9 patients, 5 men and 4 women aged 16 to 86 years. The 2D echocardiographic diagnosis was confirmed at autopsy (4 cases) or by the association of severe recurrent pulmonary embolism (5 cases). Three patients had associated ischaemic heart disease and on patient had dilated cardiomyopathy. The clinical presentation was: acute cor pulmonale (5 cases including 2 patients which biventricular myocardial infarction), chronic post-embolic cor pulmonale (1 case), tricuspid valve obstruction (1 case), general ill health with pyrexia (1 case) and heparin-induced thrombocytopenia (1 case). Predisposing factors included: absence of anticoagulent therapy (7 cases), previous supraventricular arrhythmias (2 cases) and right ventricular failure (6 cases, including 2 of right ventricular infarction). In 2 patients the thrombi were relatively immobile and had a wide base of implantation on the interatrial septum; in 1 patient, multiple thrombi were observed lining the right heart cavities from the inferior vena cava to the pulmonary infundibulum. In the other 6 patients, the thrombi were very mobile with a visible pedicule of implantation (2 cases) or totally free (4 cases). The variable polylobulated appearances, completely irregular whirling motion and intermittent prolapse into the tricuspid valve were characteristic features of the latter 4 cases. They disappeared spontaneously (2 cases) or after fibrinolytic therapy (2 cases) in under 36 hours. Three patients were operated with one postoperative death. The global hospital mortality was 22%. The present occasional detection of right atrial thrombosis will certainly become more common if patients with pulmonary embolism, right ventricular infarction or deep venous thrombosis are systematically examined by 2D echocardiography in the acute phase of their illness. PMID- 3087313 TI - [Correlations between vectorcardiographic data and effect of myocardial infarction on global and regional left ventricular function]. AB - The object of this study was to identify vector-cardiographic parameters (VCG) dependant on the size of myocardial infarction and its consequences on segmental left ventricular wall motion. Forty-five patients were selected for study after a complete haemodynamic investigation including quantitative analysis of LV wall motion. They were divided into three groups: Group I, comprising 15 normal control subjects; Group II, comprising 16 patients with abnormal LV wall motion related to anterior wall infarction due to a solitary lesion of the left anterior descending artery; Group III, comprising 14 patients with abnormal LV wall motion related either to posterior wall infarction or inferior wall infarction due to a solitary lesion of the right coronary or left circumflex arteries. Segmental wall motion was analysed by a semi-automatic programme derived from the Standford method. This programme detects the number of pathological segments in a ventricle and their shortening, and also determines a coefficient of severity of the abnormal zone. The VCG was performed according to Frank's principle and exploited using the computerised Arnaud RUBEL system. The characteristics of the instantaneous vectors were determined every 10 ms up to 60 ms: X, Y and 2 coordinates, amplitude, azimuth and elevation. These coordinates were compared with the segmental wall motion in every patient. There was a close correlation between LV regional wall motion abnormalities and the deflection of the initial vectors (during the first 40 ms) in the horizontal and frontal planes. A ROC statistical analysis showed that VCG was an excellent method of detecting abnormal LV wall motion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087314 TI - [Diagnostic value of the isoproterenol test in effort tachycardia]. AB - An isoproterenol test was performed in 69 patients during electrophysiological investigation to assess its diagnostic value in adrenergic supraventricular or ventricular tachycardia. Sixteen control subjects had no symptoms on exercise and routine exercise stress testing did not trigger any hyperexcitability. Sixteen patients had reproducible documented supraventricular tachycardia induced by exercise (13 paroxysmal junctional tachycardias, 3 focal atrial tachycardias). Eight patients had ventricular hyperexcitability related to effort. Twenty-nine patients had supraventricular and/or ventricular hyperexcitability only at rest. Electrophysiological investigations included paired atrial stimulation during sinus rhythm and paced rhythm followed by programmed ventricular stimulation using one and then two extrastimuli delivered during sinus rhythm and paced ventricular rhythm. These stimulation studies were carried out under basal conditions and then during low dose isoproterenol infusion (10 to 40 micrograms) which accelerated the heart rate to 130/mn. Electrophysiological and conduction parameters and the mode of induction of the tachycardia (defined as at least 5 successive echos with a configuration similar to the clinical tachycardia) were studied. We observed an acceleration of anterograde and retrograde conduction and a shortening of the effective atrial and ventricular refractory periods but these changes were found equally in the different groups of patients and were not related to the induction of tachycardias. The induction of paroxysmal junctional tachycardia by isoproterenol was a very sensitive (92%) and specific (100%) diagnostic method. Its diagnostic value was much greater than Holter monitoring (25%) and exercise stress testing (12.5%). Induction of ventricular tachycardia by isoproterenol was also very sensitive (75%) and specific (95%). The diagnostic value was higher than exercise stress testing (71%) and Holter monitoring (62%). Isoproterenol did not affect the induction of spontaneous tachyarrythmias unrelated to effort and even suppressed the triggering of some episodes. In conclusion, the induction by atrial or ventricular pacing or spontaneous supraventricular or ventricular tachycardia during isoproterenol infusion was very specific and correlated with the concept of tachycardia induced by exercise and therefore of adrenergic nature. The sensitivity of this test was excellent in patients with supraventricular tachycardia (95%) and very good in ventricular tachycardia (75%). On the other hand, the changes in the electrophysiological parameters were not specific for a group of patients. PMID- 3087315 TI - [Results of surgical treatment in acute native endocarditis. Apropos of 41 patients]. AB - This study was based on the analysis of 41 cases of infectious endocarditis of native valves operated during the acute phase. Patients with bacteriological cures, prosthetic valve endocarditis and endocarditis on congenital non-valvular lesions were excluded. There were 32 men and 9 women with an average age of 49 years. The valve lesions were aortic incompetence, mitral incompetence, mitro aortic disease and mitro-tricuspid disease. Fourteen patients had preexisting valvular disease (rhumatic in 12 and congenital in 2 cases). These patients were in an advanced clinical state at the time of operation: 23 Class IV, 16 Class III and 2 Class II operated for systemic embolism. The surgical indications were severe cardiac failure in 30 cases, systemic embolism in 2 cases and persistance of septicaemia with worsening cardiac function in 9 cases. The causal organism was isolated from blood cultures in 34 cases (83%) and from the excised valve in 13 cases. The early postoperative mortality during the first month was 5 patients (3 cases of aortic incompetence associated with mitral incompetence and 2 cases of aortic incompetence alone). Death was caused in most cases by irreversible cardiac failure related to the advanced preoperative cardiac failure. All the other patients were followed up for 1 to 102 months (average 44 months). There were 7 late postoperative deaths. The mortality rate was 3.4% per patient year including patients undergoing chronic haemodialysis. The actuarial survival was 79% at 78 months excluding the operative mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087316 TI - [Long-term course of septal rupture operated on during the acute phase of a myocardial infarct]. AB - Between 1970 and 1979, 28 patients (18 men and 10 women, aged 46 to 76 years, average 62 years) with acute myocardial infarction complicated by septal rupture survived surgery performed during the acute phase. In the same period 62 patients were admitted to the Cardiology Department and were operated early for septal rupture complicating myocardial infarction. The site of infarction was the anterior wall in 22 cases and the posterior wall in 6 cases; septal rupture occurred on average after 4.2 days (range 1 to 10 days); 15 patients including 13 with cardiogenic shock underwent intraaortic balloon pumping for an average of 3:7 (range 1 to 11 days) before surgery; the operation performed after an average interval of 11 days consisted in direct suture of the defect in 3 cases and a patch repair in the other 25 cases, associated in all cases with infarctectomy and LAD coronary bypass grafting in 1 case. The immediate postoperative course was simple; three patients with residual shunts were not reoperated. Five to 14 years later, in 1984, 4 patients had been lost to follow-up; 4 patients had died, 2 of cardiac causes (LVF after 1 year and an arrhythmia after 4 years). Of the 20 survivors, 2 were successfully reoperated (1 coronary bypass after 10 years and 1 false aneurysm after 5 years). Only one patient had recurrent myocardial infarction. The quality and longevity of long-term survival encourage early surgery. The factors affecting long-term survival are discussed: correction of associated valvular defects, resifual shunts, conservation of left ventricular function and evaluation of the coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087317 TI - [Coronary endarterectomy associated with by-pass. A series of 111 patients controlled angiographically]. AB - Out of 2 638 patients undergoing coronary bypass surgery at the Arnault Tzanck Centre from 1973 to September 1984, 305 (12%) also required coronary endarterectomy. One hundred and eleven of these patients had control angiographies at the Centre and were the object of this study. Endarterectomy was carried out on a totally occluded artery in 38% of cases and was performed out of necessity in the other cases. One hundred and twenty-nine disobliterations were performed in these 111 patients. The average number of bypass grafts per patient was 2.8. The overall hospital mortality was 6% (19 out of 305) which was higher than for bypass surgery alone. The postoperative myocardial infarction rate was 10%. The 117 control angiographies were performed on average during the 8th month after surgery; these controls were routine in 99 cases (84.5%) in Stage I of the NYHA classification and for recurrent angina in 18 cases (15.5%). The endarterectomised vessel was patent in 72% of cases, which was less than the patency rate of the bypass grafts. Considering the indications of necessity, this result is satisfactory and is compared which those of other reported series. PMID- 3087318 TI - [Hemodynamic evaluation of the Carpentier-Edwards porcine bioprosthesis and the Hancock pericardial bioprosthesis in aortic position]. AB - Forty-four asymptomatic patients were catheterised at Boucicaut Hospital 9.5 months after aortic valve replacement to assess the haemodynamic performances of 21 Hancock pericardial (HP) and 23 porcine Carpentier-Edwards (CE) (standard model) bioprostheses, implanted in the aortic position. Left heart catheterisation was performed from a femoral approach; the simultaneous gradient was measured by planimetry and the functional valve surface area calculated at rest and after exercise. The resting calculated surface area of the HP was greater than that of the CE bioprostheses (equation: see text). The transvalvular pressure gradient was lower in the HP than in the CE group (7.8 +/- 4 vs 15.3 cf243 6 mmHg; p less than 0.005). After exercise (15 patients) the calculated surface area increased with the increased transvalvular blood flow in both groups but at each flow rate the calculated valve surface area was greater in the HP group. The haemodynamic performance of the CE bioprosthesis is inferior to that of the HP bioprosthesis, especially in the smaller models. However, the CE bioprosthesis would seem to be mechanically more reliable in the long term than the HP bioprosthesis has since been withdrawn from the market. PMID- 3087319 TI - [Spatial ventricular gradient studied by computerized vectorcardiography. Normal and pathological values. Interpretation and clinical evaluation]. AB - The ventricular gradient is a reflection of uneven ventricular repolarisation. Until recently is was only appreciated in the frontal plane of the classical electrocardiogramme and expressed as the sum of the vectors representing the surfaces under the QRS complex and T wave. We used computerised vectorcardiography to obtain a more exact evaluation of the size and spatial orientation of the vector gradient. The spatial vector gradient was calculated in a control group and in a number of pathological conditions. The reference values were established in 70 normal subjects with a mean age of 36 +/- 21 years: 0.092 +/- 0.016 m V.s for amplitude: 38.4 degrees +/- 6.1 for thesite and 21.6 degrees +/- 8.7 for the azimuth. The size and spatial orientation of the ventricular gradient can be used to define normal limits and to distinguish subgroups by using the values of the site and azimuth. The spatial ventricular gradient is a new approach to defining the limits of normality in poorly understood abnormalities of ventricular repolarisation. It may also be useful in the comprehension of certain forms of cardiac arrhythmia related to desynchronisation of ventricular repolarisation. PMID- 3087320 TI - [Antiarrhythmic effects of intravenous magnesium sulfate in torsade de pointes. Apropos of 6 cases]. AB - The antiarrhythmic properties of magnesium salts, known for many years, are periodically recalled but rarely used in daily clinical practice. They are usually used in digitalis-induced arrhythmias and are rarely indicated in other conditions; they are often reserved for cases in which a magnesium deficiency is suspected. In 6 cases of torsades de pointes, magnesium sulphate was administered at a dose 1 to 3 g by direct intravenous injection. Although hypokalaemia was a common finding, a low magnesium concentration was only found in one case. The ventricular arrhythmia regressed completely at the end of the injection in 4 cases (one after two injections). One positive but incomplete response was observed in the only case of magnesium deficiency, probably due in retrospect to inadequate dosage. Finally, one patient with very poor ventricular function had recurrence after a good initial response. The diversity of the clinical and biological findings in this series suggests a specific antiarrhythmic action of the magnesium ion, apparently independant of the correction of magnesium deficiency; experimental studies suggest that the mode of action is a direct antagonism of Mg++-K+ and/or Mg++-Ca++. Compared to usual means of treatment of torsades de pointes (isoprenaline infusion or pacing) the advantages of intravenous magnesium sulphate are clear-cut: innocuity, simplicity and rapidity of administration, and almost immediate efficacy. PMID- 3087321 TI - [Secondary tumors of the right heart. Echocardiographic aspects. Apropos of 6 cases in the adult]. AB - Secondary cardiac tumours are rare but but are now more frequently diagnosed by echocardiography. We report 6 cases of intracardiac metastases affecting the right heart which were diagnosed by 2D echocardiography. In 3 cases, a very mobile, oval-shaped tumour was visualised within the right atrium prolapsing into the tricuspid orifice in diastole like a myxoma but associated in 2 cases with signs of invasion of the inferior vena cava. Two other non-mobile tumours were observed causing massive invasion of the right atrium and the last case was of an infiltrating tumour of the right ventricle resulting in pulmonary infundibular obstruction. In the light of our experience and a review of the literature, it is difficult to distinguish secondary tumours of the right atrium from myxomas especially when the tumours are mobile and when it is impossible to visualise a pedicle inserted on the interatrial septum or tumoral invasion of the inferior vena cava. At the ventricular level, the diagnostic signs differ according to whether there is tumoral invasion of the cavity or infiltration of the muscular wall. These cases illustrate the value of 2D echocardiography in the diagnosis of intracardiac metastases, sometimes even in the absence of clinical signs. PMID- 3087322 TI - [Surgical anatomy of the interventricular communications of the septal trabecula]. AB - Muscular ventricular septal defects (VSD) are a special anatomical and surgical entity. They are observed in 85% of cases of multiple VSD. This study was based on the operative findings in 70 patients and 20 pathological specimens of muscular VSD. A surgical topographic classification is proposed, superior, intermediate and inferior, with a specific surgical approach for each of the three types. The superiorly situated muscular VSDs are approached through the right ventricle, the intermediate ones through the right atrium and the inferior through the right atrium or left ventricle. Section of the moderator band greatly facilitates the exposure of the intermediate and inferior segments of the septum through the tricuspid valve. Left ventriculotomies should be reserved for inferiorly situated muscular VSD with right ventricles of small volume. PMID- 3087323 TI - [Balloon catheter dilation of severe pulmonary restenosis 11 years after surgical valvulotomy]. AB - A young girl who underwent repair of an atrial septal defect and pulmonary valvulotomy when 6 years of age, presented with clinical and haemodynamic signs of pulmonary restenosis 11 years later: right ventricular systolic pressure (RVSP) of 130 mmHg with a systolic RV/PA pressure gradient of 105 mmHg. Pulmonary valvuloplasty was performed using a balloon catheter (20 mm X 40 mm). Two inflations were necessary to correct the hour glass deformity of the balloon caused by the stenosis. After valvuloplasty the RVSP was 75 mmHg and the RV/PA gradient 55 mmHg. The calculated pulmonary valve surface area increased from 0.36 cm2 to 0.72 cm2. Angiography performed immediately after dilatation showed improved valvular mobility but here was persistant severe infundibular hypertrophy. The intensity of the pulmonary systolic murmur decreased. The good result obtained in this case shows that percutaneous valvuloplasty may be considered when restenosis occurs several years after surgical valvulotomy. Control catheterisation performed two months after dilatation confirmed the good initial haemodynamic result. PMID- 3087324 TI - [Cinchona alkaloids and cardiac arrhythmias]. PMID- 3087325 TI - Deoxyribonucleic acid replication time in Mycobacterium tuberculosis H37 Rv. AB - The DNA increment method, designed for measuring the increment in the amount of DNA after inhibition of initiation of fresh rounds of replication initiation was employed to measure the rate of deoxyribonucleic acid (DNA) chain growth in Mycobacterium tuberculosis H37Rv growing in Youman and Karlson's medium at 37 degrees C with a generation time of 24 h and also in relatively fast growing species like Mycobacterium smegmatis and Escherichia coli. From the results obtained, the time required for a DNA replication fork to traverse the chromosome from origin to terminus (C period) was calculated. The chain elongation rates of DNA of the three organisms was determined from the C period and the known genome sizes assuming that all these genomes have a single replication origin and bidirectional replication fork. The rate for M. tuberculosis was 3,200 nucleotides per min about 11 times slower than that of M. smegmatis and about 13 18 times slower than that of E. coli. PMID- 3087326 TI - [A rare cause of obstruction of the posterior urethra: bladder diverticulum]. PMID- 3087327 TI - Efficacy of tissue plasminogen activator and urokinase in a canine model of prosthetic graft thrombosis. AB - Tissue plasminogen activator and urokinase were evaluated in a model of prosthetic graft thrombosis. In addition, the effects of thrombus age on lysability and the effect of thrombolytic agents on endothelium were examined. Polytef (polytetrafluoroethylene [PTFE]) grafts (3 mm X 3.5 cm) were placed in femoral arteries of dogs and graft thrombosis was induced. Grafts were treated with a local infusion of either urokinase or tissue plasminogen activator (4000 units/min) and the times for initial flow, complete thrombolysis, and anastomotic bleeding were noted. The luminal surfaces of the grafts and the proximal arterial segments were assayed for the production of thromboxane A2 and prostacyclin and examined with scanning electron microscopy. No difference in the ease of graft lysis was observed, but 50% of tissue plasminogen activator-treated vs 0% of urokinase treated grafts had extravasation of blood through the wall. Grafts treated with tissue plasminogen activator produced less thromboxane A2 and had less thrombus than those treated with urokinase. No differences between arteries exposed to either agent and control arteries were seen. Grafts treated 1,3,5, and 7 days after thrombosis were progressively more difficult to lyse. We conclude that tissue plasminogen activator is an effective thrombolytic agent, but has a potential for local bleeding complications. Grafts of PTFE are thrombogenic after lysis, but may be less so with tissue plasminogen activator than with urokinase. No effect on arterial endothelium was seen, and our studies confirm the clinical impression that older thrombi are more difficult to lyse. PMID- 3087328 TI - Pharmacokinetic aspects of drug effects in vitro: effects of serum protein binding on concentration and teratogenicity of valproic acid and 2-en-valproic acid in whole embryos in culture. AB - Pharmacokinetic studies were performed in connection with culture experiments. Using the technique of cultivating whole rat embryos of the early postimplantation stage, we measured the concentration of valproic acid (VPA) and 2-en-VPA in the culture medium (free and protein-bound form) and in embryonic tissue. The following results were obtained: The concentrations of VPA and 2-en VPA reached in the embryos were lower than corresponding total concentrations added to the culture medium, but exceeded the free concentrations in the medium. The concentrations of 2-en-VPA found in the embryo were lower than the comparable VPA total levels because of the more extensive protein binding of 2-en-VPA in the culture serum. The percentage of binding to serum proteins decreased with increasing total drug concentrations in the medium; the concentration of the free drug in the medium increased overproportionally with increasing total drug concentrations. Therefore, the free drug concentrations in the medium were not proportional to the dose of the drug dissolved in the medium (for a drug bound to plasma proteins). The concentrations of VPA and 2-en-VPA found in the embryos after incubation in vitro were not proportional to the drug concentrations dissolved in the medium. This result has to be taken into account when dose response relationships are evaluated. VPA concentrations of 40 micrograms/g wet weight and above in the embryos clearly induced abnormal development in about 30% of the embryos, while 2-en-VPA concentrations as high as 200 micrograms/g embryo (wet weight) were inactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087330 TI - [Effect of aspirin on exercise-induced bronchospasm]. PMID- 3087331 TI - Focal scleral mucinosis. PMID- 3087329 TI - Comparison of the effectiveness of several chelators after single administration on the toxicity, excretion and distribution of cobalt. AB - The effects of the chelating agents Na2Ca-ethylendiaminetetraacetate (EDTA), Na3Ca-diethylentriaminepentaacetate (DTPA), L-cysteine, 2,3-dimercaptosuccinic acid (DMSA), N-acetyl-L-cysteine (NAC), glutathione, D,L-penicillamine (D,L-PEN) and 2,3-dimercaptopropanol (BAL) on the toxicity, distribution and excretion of intraperitoneally injected cobalt were studied in male Swiss mice. To determine the effect of the various chelators on the toxicity of cobalt, various doses of CoCl2 (0.60-1.80 mmol/kg) were given, followed immediately by the IP administration of the chelator (at a dose equal to one-fourth of their respective LD50). EDTA and DTPA were the most effective. EDTA, DTPA and L-cysteine, NAC and glutathione were also the most effective in increasing the urinary excretion of cobalt and reducing the concentration of the metal in various tissues. EDTA appears to be the most effective agent of those tested in the prevention of acute cobalt intoxication. PMID- 3087332 TI - Secretion of the beta-subunit of luteinizing hormone in dispersed rat anterior pituitary cells. PMID- 3087333 TI - A prospective study of the metabolic effects of a low dose combined oral contraceptive. PMID- 3087334 TI - Development and use of appropriate technology for health. PMID- 3087335 TI - Multiple central venous line occlusions following an error in parenteral nutrition formulation. AB - Multiple occlusions of central venous catheters occurred in four patients who were receiving total parenteral nutrition (TPN). Misformulation of bulk prepared TPN solution caused temperature-dependent precipitation of calcium phosphate within the catheter during infusion. PMID- 3087336 TI - Ethical problems associated with the treatment of intestinal failure. PMID- 3087338 TI - The medicalization of aboriginal children: a comparison of the lengths of hospital-stay of aboriginal and non-aboriginal children in Western Australia and the Northern Territory. AB - This paper compares the lengths of hospital-stay of Aboriginal and non-Aboriginal children in Western Australia and the Northern Territory over the past few years. The comparison yields two trends: Aboriginal children stay longer in hospital than do non-Aboriginal children; within each racial group, children stay longer in hospital in the Northern Territory than in Western Australia. By-and-large, these trends continue irrespective of age, sex, diagnostic category, hospital and usual place of residence. It appears that factors in addition to high rates of infectious disease, severity of illness and remoteness of home address affect length of hospital stay. Two organizational factors are suggested: the latent, working logic of service institutions such as public hospitals and the tendency of government to institutionalize impoverished people. It is concluded however, that as health care becomes holistic and more the responsibility of Aboriginal people, there is every reason to predict a decrease in the lengths of hospital stay of Aboriginal children. PMID- 3087337 TI - Therapeutic drug monitoring in childhood. PMID- 3087339 TI - Gastrointestinal hypersensitivity to cow's milk protein: the diagnostic value of gut function tests. AB - Thirty-six children with suspected gastrointestinal hypersensitivity to cow's milk protein were investigated before and after challenge with cow's milk protein by one or more of four tests of gut function: the appearance of small bowel mucosa, mucosal disaccharidase levels, a 1-h blood-xylose test, and a 50 g lactose breath-hydrogen test. These tests were not always abnormal in children who had definite adverse reactions to milk. Conversely changes were seen in some with negative milk challenges. Although small bowel biopsy, assessment of disaccharidase activity and perhaps the breath-hydrogen test have an important place in the pre-challenge assessment to exclude other causes of gastrointestinal symptoms, these gut function tests and the 1-h xylose test done following milk provocation do not appear to have any advantage over careful clinical observation. PMID- 3087340 TI - Biotin-reversible neurodegenerative disease in infancy. AB - Two siblings with consanguineous parents began having myoclonic jerks at age 5 months after introduction of mixed feeding. There was later developmental regression. The elder girl died without diagnosis aged 1 year, after prolonged continuous hyperventilation. The younger sibling did not have metabolic acidosis when first investigated for myoclonus and hypotonia aged 5 months. At 9.5 months, when intermittently decerebrate and hyperventilating, she had a metabolic acidosis with elevated blood lactic, pyruvic and beta-hydroxybutyric acids, and beta-hydroxyisovaleric aciduria. On the assumption that she had beta methylcrotonyl-CoA carboxylase deficiency she was started on biotin, 10 mg daily. Within 36 h there was dramatic clinical and biochemical improvement. Previously defective eye movement control and gaze became normal, hyperventilation ceased, and excessive organic acid excretion in urine was abolished. She remains on long term biotin and at age 2 years her development appears normal in all respects. Fibroblast culture however revealed normal quantities of the enzymes beta methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase and pyruvate carboxylase. Irrespective of niceties of enzyme and organic acid biochemistry, the clinician must be aware of biotin-reversible regressive brain disease which may present before manifest metabolic acidosis. PMID- 3087341 TI - [Modern methods for the manufacture of therapeutic coagulation factors]. AB - In a modern therapy concept coagulation factor concentrates are widely used for prophylaxis of bleeding events and in intensive care medicine. In the past their use was limited by the risk of transmitting virus diseases to the patient. Therefore, it was a challenge to modern plasma fractionation to develop purification processes which are able to eliminate and inactivate viruses. At present several methods for virus inactivation are used; their efficiency is not finally proven. Practical experience exists with a method in which viruses are inactivated by heat treatment in solution. A similar process is used since more than 40 years to produce albumin and was proven to be safe. Today, all coagulation factor preparations can be treated by this inactivation method and produced in large scale. Together with a high degree of viruses elimination during the purification process the therapy with coagulation factors has become much safer. PMID- 3087342 TI - Inter- and intraspecific variation in the response of Drosophila melanogaster and D. simulans to larval cues. PMID- 3087343 TI - Variation in sexual behavior and negative assortative mating in Drosophila melanogaster. PMID- 3087345 TI - Removal of N-terminal methionine from haemoglobin nascent peptides by a membrane bound rat liver methionine aminopeptidase. AB - A membrane-bound aminopeptidase able to remove methionine from haemoglobin nascent peptides is described. The enzyme also hydrolyses methionine from methionyl-lysyl-bradykinin but not lysine from lysyl-bradykinin. The tripeptide Met-Ala-Ser is poorly hydrolysed. This aminopeptidase also splits amino acid 2 naphthylamides, being, however, less specific with respect to these synthetic substrates. PMID- 3087346 TI - Diagnosis of Maroteaux-Lamy syndrome by the use of radiolabelled oligosaccharides as substrates for the determination of arylsulphatase B activity. AB - The kinetic parameters (Km and V) of human arylsulphatase B (4-sulpho-N acetylgalactosamine sulphatase) activity in cultured skin fibroblasts were determined with a variety of substrates matching structural aspects of the physiological substrates in vivo chondroitin 4-sulphate and dermatan sulphate. More structurally complex substrates, in which several aspects of the aglycone structure of the natural substrate were maintained, were desulphated up to 4400 times faster than the minimum arylsulphatase-B-specific substrate, namely the monosaccharide N-acetylgalactosamine 4-sulphate. Aglycone structures that influence substrate binding and/or enzyme activity were an adjacent-residue C-6 carboxy group and a second but internal N-acetylgalactosamine 4-sulphate residue. Arylsulphatase B activity in fibroblast homogenates assayed with O-(beta-N acetylgalactosamine 4-sulphate)-(1----4)-O-D-(beta-glucuronic acid)-(1----3)-O-D N-acetyl[1-3H] galactosaminitol 4-sulphate derived from chondroitin 4-sulphate as substrate clearly distinguished Maroteaux-Lamy-syndrome patients from normal controls and other mucopolysaccharidosis patients. We recommend the use of the above trisaccharide substrate for both postnatal and prenatal diagnosis of Maroteaux-Lamy syndrome. PMID- 3087347 TI - Binding of hyaluronate and chondroitin sulphate to liver endothelial cells. AB - Hyaluronate is taken up and metabolized in liver endothelial cells by means of a receptor. To characterize the interaction with the receptor, two preparations of 3H-labelled hyaluronate, of Mr 4 X 10(5) and 6.4 X 10(6), and a series of hyaluronate oligosaccharides were bound to cultured liver endothelial cells at 7 degrees C. The dissociation constant varied between 4.6 X 10(-6) M for an octasaccharide and 9 X 10(-12) M for the largest polymer. The Mr-dependence for the series of oligosaccharides was explained by the increased probability of binding due to the repetitive sequence along the chain. The high affinity of high Mr hyaluronate for the receptor could also be mainly ascribed to this effect, which rules out any major contribution of co-operative multiple-site attachment to the cell surface. Each liver endothelial cell can bind 10(5) oligosaccharides, about 10(4) molecules with Mr 4 X 10(5) and about 10(3) molecules with Mr 6.4 X 10(6). This is explained by mutual exclusion of large molecules from the cell surface. Chondroitin sulphate is also bound to liver endothelial cells. Inhibition studies showed that it binds to the same receptor as hyaluronate and with an affinity that is about 3-fold higher than that of hyaluronate of the same degree of polymerization. PMID- 3087344 TI - Recent advances in the biochemistry of polyamines in eukaryotes. PMID- 3087349 TI - Beta carotene is associated with the regression of hamster buccal pouch carcinoma and the induction of tumor necrosis factor in macrophages. AB - Beta carotene (250 micrograms/ml) dissolved in mineral oil applied either topically or injected locally (190 ng/ml dissolved in media) into DMBA (7,12 dimethylbenz(a)anthracene)-induced or HCPC-1 cell line-produced oral squamous cell carcinoma of the hamster buccal pouch was observed to result in the regression of these tumors. (p less than or equal to .005) Beta carotene application to tumor bearing pouches was observed to produce a dramatic increase in positively stained macrophages for tumor necrosis factor (TNF-alpha) as compared to macrophages in control pouches. Macrophages from hamsters with regressed tumor were shown to produce a significant increase in cytotoxicity to HCPC-1 tumor cells. Regression of the hamster oral carcinoma was correlated with the increased capacity of macrophages to lyse tumor cells, and related to the induction of tumor necrosis factor which was associated with the administration of the carotenoid, beta carotene. PMID- 3087348 TI - Absence of diamine oxidase activity from rabbit and rat lungs. AB - To study the presence of diamine oxidase (DAO) activity in any tissue with putrescine as the substrate, it is necessary to use inhibitors to block all pathways that could further metabolize gamma-aminobutyraldehyde, which is the product of enzyme reaction. It is also necessary to inhibit any enzyme that may convert putrescine into higher polyamines. By this approach it was observed that lung tissue of both rat and rabbit exhibited no DAO activity. DAO activity was observed in the rat and rabbit intestine, the former showing 3 times as much activity as the latter. The other potential pathways of putrescine metabolism are of no consequence in the rat and rabbit intestine and lungs. PMID- 3087351 TI - The effects of a calcium and a sodium ionophore on protein synthesis inhibition by a bovine cell surface sialoglycopeptide. AB - The ability of the calcium ionophore A23187 and the sodium ionophore Monensin to antagonize the inhibition of 3T3 cell protein synthesis by a bovine cell surface sialoglycopeptide was measured. A23187, when added before and shortly after the sialoglycopeptide, significantly reduced the biological activity of the inhibitory glycopeptide. In contrast, Monensin had little, if any, influence on protein synthesis inhibition by the sialoglycopeptide. The ability of A23187 to circumvent the inhibitory action of the bovine glycopeptide was shown to be independent of the time the ionophore was incubated with the cells and the binding of the sialoglycopeptide to the 3T3 target cells. Neither the total amount of sialoglycopeptide bound to the cells, nor its affinity to the cell surface receptor, was influenced by the presence of A23187. PMID- 3087350 TI - Inhibin and beta type transforming growth factor (TGF beta) have opposite modulating effects on the follicle stimulating hormone (FSH)-induced aromatase activity of cultured rat granulosa cells. AB - We have recently observed that attomolar concentration of exogenously added TGF beta, a molecule structurally related to inhibin, can stimulate the basal secretion of FSH in a pituitary cell culture. Inhibin purified from porcine follicular fluid antagonizes this activity of TGF beta. To understand further the homeostatic regulatory properties of inhibin and TGF beta we have investigated whether the aromatase activity of ovarian granulosa cells is also subject to intra-ovarian modulation by these peptides. Granulosa cells from immature hypophysectomized diethylstilbestrol-treated rats were cultured for 2 days with androstenedione (10(-7) M) as a substrate, oFSH (2 ng), and different amounts of TGF beta or inhibin. Basal estrogen secretion was negligible and remained unaffected by treatment with purified TGF beta or inhibin (10 ng/ml), whereas treatment with oFSH (2 ng/ml) produced a 100-fold increase in estrogen accumulation. The concurrent application of increasing concentrations (10 pg-10 ng/ml) of TGF beta produced dose-dependent increments in the FSH-stimulated accumulation of estrogen with a ED50 of 0.3 +/- 0.02 ng/ml. On the other hand, concurrent incubation of FSH with inhibin ranging from 10 pg to 10 ng/ml decreases the FSH-mediated estrogen secretion. TGF beta antagonizes the inhibition of inhibin on aromatase activity. These findings suggest that inhibin and TGF beta, two closely related molecules, play novel and opposite roles in modulating the follicular functions. PMID- 3087353 TI - The anticoagulant properties of mast cell product, chondroitin sulphate E. AB - The anticoagulant potency in vitro of chondroitin sulphate E has been found to be similar to that of the heparinoids. In purified systems chondroitin sulphate E was shown to be principally an activator of heparin cofactor II. Maximum acceleration of heparin cofactor II:thrombin interaction was 185-fold (9.3 X 10(7) M-1 min-1), antithrombin III:thrombin interaction was 11-fold (4.16 X 10(6) M-1 min-1) and antithrombin III:factor Xa was 146-fold (3.86 X 10(6) M-1 min-1). Chondroitin sulphate E was observed to prolong the thrombin clotting time of fibrinogen in the absence of antithrombin III and heparin cofactor II. The effect appeared to be related to interference in thrombin:fibrinogen interaction rather than in fibrin monomer polymerization. PMID- 3087352 TI - The amino acid sequence of kinetensin, a novel peptide isolated from pepsin treated human plasma: homology with human serum albumin, neurotensin and angiotensin. AB - A novel nonapeptide with neurotensin-like immunoreactivity was isolated from pepsin-treated human plasma by dialysis, ion-exchange chromatography and high performance reversed-phase liquid chromatography. The amino acid sequence was determined by automated gas-phase sequence analysis as Ile-Ala-Arg-Arg-His-Pro Tyr-Phe-Leu. Sequence homology with human serum albumin and with the biologically active peptides neurotensin and angiotensin is demonstrated. The name proposed for this peptide is kinetensin. PMID- 3087354 TI - Forskolin stabilizes a functionally coupled state between activated guanine nucleotide-binding stimulatory regulatory protein, Ns, and catalytic protein of adenylate cyclase system in rat erythrocytes. AB - Guanine nucleotide-binding stimulatory regulatory protein of adenylate cyclase system, Ns, in rat erythrocytes was activated by the treatment with guanylyl 5' imidodiphosphate or NaF-AlCl3 in the presence of Mg2+. The activation was counterbalanced to the basal state either by the removal of Mg2+ or by the addition of beta(gamma)-subunit of N protein of this system. The depression from the activated state was markedly protected by the coexistence of forskolin at the time of the deactivation depending on the dose of forskolin. EC50 of forskolin for the stabilizing effect was much lower than that for the stimulation of adenylate cyclase activity. These data indicate that forskolin has an effect on the interaction between Ns and catalytic unit of adenylate cyclase system in addition to the direct effect on the catalytic unit. PMID- 3087355 TI - Selective inhibition of leukotriene C4 synthesis in human neutrophils by ethacrynic acid. AB - Addition of glutathione S-transferase inhibitors, ethyacrynic acid (ET), caffeic acid (CA), and ferulic acid (FA) to human neutrophils led to inhibition of leukotriene C4 (LTC4) synthesis induced by calcium ionophore A23187. ET is the most specific of these inhibitors for it had little effect on LTB4, PGE2 and 5 HETE synthesis. The inhibition of LTC4 was irreversible and time dependent. ET also had little effect on 3H-AA release from A23187-stimulated neutrophils. PMID- 3087356 TI - Phorbol ester stimulates the synthesis and phosphorylation of a 48 kDa intracellular protein in plasminogen activator secreting melanoma cells. AB - Phorbol ester (12-O-tetradecanoyl-phorbol 13-acetate) stimulates the secretion of tissue-type plasminogen activator by the melanoma cell line, Bowes. This effect is associated with increased levels of mRNAs for both tissue-type plasminogen activator and a 48 kDa-protein. Labelling of melanoma cells with L [35S]methionine allowed to identify an intracellular protein which, by 3 criteria, was identical with the in vitro translation product of the 48kDa protein mRNA: a Mr of 48,000 on electrophoresis in the presence of sodium dodecyl sulphate; inducibility by phorbol ester and failure of reducing agents to affect electrophoretic mobility. As detectable by L-[35S]methionine labelling, the protein was mainly localized in the cytosol. In vitro phosphorylation reactions, carried out on subcellular fractions revealed a membrane-associated protein which also had the three characteristics of the aforementioned 48 kDa-protein. Phosphorylation did not require Ca2+-ions. Addition of phorbol ester to the reaction mixtures increased the phosphorylation. Reconstitution experiments between membrane and cytosol fractions of phorbol ester-treated and untreated cells showed that the 48kDa protein occurs in a cytosolic, unphosphorylated and a membrane-bound, phosphorylated form and that the former is converted to the latter by a phorbol ester activated, membrane-associated protein kinase. PMID- 3087357 TI - Increases in cellular calcium concentration stimulate pepsinogen secretion from dispersed chief cells. AB - Intracellular calcium concentration ([Ca]i) and pepsinogen secretion from dispersed chief cells from guinea pig stomach were determined before and after stimulation with calcium ionophores. [Ca]i was measured using the fluorescent probe quin2. Basal [Ca]i was 105 +/- 4 nM. Pepsinogen secretion was measured with a new assay using 125I-albumin substrate. This assay is 1000-fold more sensitive than the widely-used spectrophotometric assay, technically easy to perform, rapid, and relatively inexpensive. The kinetics and stoichiometry of ionophore induced changes in [Ca]i and pepsinogen secretion were similar. These data support a role for calcium as a cellular mediator of pepsinogen secretion. PMID- 3087359 TI - Differences in the spectral interactions between NADPH-cytochrome P-450 reductase and a series of cytochrome P-450 enzymes. AB - The interaction between NADPH-cytochrome P-450 reductase and a series of cytochrome P-450 isozymes was investigated using UV-visible spectrophotometry. In the absence of substrate the interactions between the reductase and RLM3, RLM5, and RLM5a were tight, exhibiting sub-micromolar dissociation constants and resulted in type I spectra of varying magnitude from which the following increases in the proportion of high spin hemoprotein were calculated; RLM3 (7%), RLM5 (36%), RLM5a (6%), LM2 (29%), RLM2 (0%). Preincubation of LM2 with its type I substrate benzphetamine increased the affinity of the cytochrome for the reductase. Using initial estimates of the P-450 spin states in the absence of reductase in conjunction with the spectral binding data and equations relating these parameters to the microequilibria for the association of reductase with high or low spin P-450, RLM3, RLM5, RLM5a and LM2 were shown to bind significantly more tightly to high spin P-450. The relevance of this data to the understanding of spin state influence on P-450 reduction is discussed. PMID- 3087358 TI - Phosphorylation of p36 in vitro by protein kinase C. AB - The 36kDa subunit of protein I (p36) is a major substrate of several tyrosine protein kinases. Here we demonstrate that protein kinase C catalyzes the incorporation of 1.7 moles of phosphate per mole of protein I. Phosphorylation is absolutely dependent on the presence of both calcium and phospholipid, and is specific for serine and threonine residues. Phosphorylation of protein I by the c AMP dependent protein kinase, phosphorylase kinase, casein kinase I, and casein kinase II was not observed. The in vivo significance of protein kinase C dependent phosphorylation of p36 is discussed. PMID- 3087360 TI - Apolipoprotein B is a calcium binding protein. AB - Human hepatocarcinoma Hep G2 cells were grown in culture medium containing [45Ca2+]. The secreted lipoproteins of d less than 1.063 g/ml and d 1.063-1.21 g/ml were isolated from the culture media and analyzed by 3.3% and 7% SDS polyacrylamide gel electrophoresis. Radioactivity profiles of [45Ca] from the gels showed that the peak of radioactivity corresponded to the apolipoprotein B band. The molar ratio of the incorporated [45Ca2+] and apolipoprotein B was close to unity. No radioactivity was found associated with any other secreted apolipoproteins. To confirm these findings, apolipoprotein B-containing lipoproteins were precipitated with anti-apolipoprotein B and high density lipoproteins were precipitated with anti-apolipoprotein A-I. Only the former precipitate was radioactive. These results suggest that apolipoprotein B is a calcium binding protein. PMID- 3087361 TI - Identification of the C-terminus of rabbit skeletal muscle glycogen synthase. AB - The primary structure of a tryptic peptide containing one of the phosphorylation sites on rabbit skeletal muscle glycogen synthase (site 1b) has been redetermined and shown to correspond to the C-terminus of the protein. The sequence is: SNSVDTSSLSTPSEPLSSAPSLGEERN. PMID- 3087362 TI - Preparation and sequencing of the cloacin fragment of Streptomyces aureofaciens 16S RNA. AB - A fast method for isolation of a 3'-terminal fragment of Streptomyces aureofaciens 16S RNA was developed. The procedure involves reaction of 70S ribosomes with cloacin DF13 and subsequent fractionation of the reaction mixture by polyacrylamide gel electrophoresis. The cloacin fragment was eluted from the gel and used directly for 3'-end labeling with cytidine-3',5'-[5' 32P]bisphosphate. The labeled RNA fragment was sequenced by the enzymatic method. It consists of 50 nucleotides and has the sequence 5'-GUCGUAACAAGGUAACCGUACCGGA AGGUGCGGUUGGAUCACCUCCUUUCOH. The differences from the E. coli and Bacillus sequences and their possible influence on the rate and specificity of polypeptide synthesis are discussed. PMID- 3087363 TI - Miconazole inhibition of platelet aggregation by inhibiting cyclooxygenase. AB - Platelet dysfunction was found in rabbits to which a dose of miconazole nitrate (1.6 mg/kg body wt) therapeutic for human subjects had been given intravenously. The present experiments were conducted to elucidate the mechanism of inhibitory effects of miconazole on platelet function. After administration of a single dose of miconazole, rabbit platelet aggregation induced by collagen and sodium arachidonate was inhibited significantly for approximately 24 hr. On the other hand, hypertriglycemia, one of the major side effects of this drug, was not seen during 2 days of observations, nor were any other outstanding manifestations observed. In in vitro experiments, miconazole nitrate (10 microM) also significantly inhibited rabbit and human platelet aggregation (P less than 0.01). Biochemical analyses revealed that the stimulant-induced formation of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), metabolites via cyclooxygenase, was inhibited by miconazole nitrate in both human and rabbit platelets in vitro. PGE2 production was decreased dose-dependently with the increase of miconazole concentration (10 to 100 microM), and the decrease was in parallel with a decrease of TXB2 production. In addition, malondialdehyde (MDA) production of human and rabbit platelets induced by exogenous arachidonate and collagen was also inhibited significantly by miconazole. Chromatographic studies showed that the amount of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), a metabolite via lipoxygenase, was increased markedly in accordance with the miconazole-induced decrease of TXB2 and 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) formation in both human and rabbit platelets. These results indicate that miconazole nitrate inhibits platelet cyclooxygenase, without affecting the stimulant-induced release of arachidonic acid from platelet phospholipids. Use of this drug in the treatment of systemic fungal infection appears to be increasing. Careful attention should be paid to the inhibitory effects of miconazole on platelet function, especially in the case of intravenous treatment. PMID- 3087364 TI - Verapamil depresses the synthesis of lipoxygenase products by hypoxic cardiac rat fibroblasts in culture. AB - Lipoxygenase metabolites of arachidonic acid are potent chemotactic and vasoconstrictive agents and their local production in the myocardium induces the migration of polymorphonuclear cells into ischemic myocardium. These cells have been shown to play a role in the development of ischemic myocardial lesions. In the present study, the synthesis of arachidonic acid lipoxygenase metabolites by rat cardiac cells in culture and the effect of verapamil were investigated under normal and hypoxic conditions. Myocytes and fibroblasts metabolized exogenous arachidonic acid into 12-HETE and an unidentified metabolite (X). Fibroblasts synthesized significantly greater amounts of 12-HETE than myocytes (P less than 0.01). Hypoxia (glucose-free medium and low PO2) and verapamil (10(-7) M) under normal conditions, did not change metabolite synthesis by either type of cells. Under hypoxia, verapamil decreased significantly 12-HETE and X production by fibroblasts (P less than 0.01 and P less than 0.05), whereas the synthesis in myocytes was not changed. It is concluded that the decrease in lipoxygenase product synthesis under hypoxia by verapamil may contribute to its therapeutic effects on the ischemic heart. PMID- 3087365 TI - Ionophore-dependent generation of eicosanoids in human dispersed lung cells. Modulation by 6,9-deepoxy-6,9-(phenylimino)-delta 6,8-prostaglandin I1 (U 60,257). AB - 6,9-Deepoxy-6-9-(phenylimino)-delta 6,8-prostaglandin I1, a prostacyclin analogue reported to inhibit sulphidopeptide leukotriene formation in animals, was evaluated for its pharmacological activity against eicosanoid and histamine release from human dispersed lung cells (HDLC). In the absence of drug, challenge of HDLC with A23187 (2.5 microM) increased immunoreactive eicosanoid generation by factors of 7.6 for prostaglandin (PG) D2, 9.1 for TXB2, 3.2 for PGF2 alpha, 2.0 for 5-HETE, 6.3 for LTC4, in association with a twofold increase in histamine release. When exogenous [14C]-arachidonic acid was added to HDLC simultaneously with A23187 challenge, radiolabelled eicosanoids were recovered in the supernatant, but on separating the products by radio-thin layer chromatography the proportions of individual eicosanoids were not significantly different from unchallenged cells. With endogenous arachidonate, U-60,257 was a potent inhibitor of i-LTC4 generation at 1 microM, but between 3 and 300 microM there was a concentration-related reversal of this inhibition. The effects of U-60,257 on the metabolism of exogenous [14C]-arachidonic acid were also studied. Under these circumstances the drug was a potent inhibitor of both 5-HETE and 5,12-diHETE formation, without significantly affecting the formation of other mono-HETES. In agreement with previous endogenous substrate experiments there was a concentration-dependent inhibition of TxB2 formation from exogenous arachidonic acid. These findings highlight the complex pharmacological actions of U-60,257 which appear dependent on the source of arachidonic acid substrate. PMID- 3087366 TI - Decrease in lipogenesis and glucose oxidation of rat adipose tissue after chronic ethanol feeding. AB - This investigation was performed to determine whether chronic ethanol feeding affects adipose tissue lipogenesis and glucose metabolism. Female Wistar rats were pair-fed nutritionally adequate liquid diets containing ethanol as 36% of energy or an isocaloric amount of carbohydrate for 3 weeks. Chronic ethanol feeding resulted in a depression of adipose tissue lipogenesis as assessed by labeled glucose incorporation into glyceride glycerol and glyceride fatty acids. Glucose oxidation was also impaired after chronic ethanol feeding. Such changes may contribute to the postprandial hypertriacyglyceridemia observed in alcoholics. PMID- 3087367 TI - Metallothionein in cultured human epithelial cells and synovial rheumatoid fibroblasts after in vitro treatment with auranofin. AB - Radioimmunoassay (RIA) and reversed-phase high-pressure liquid chromatography (HPLC) were used to investigate gold-binding proteins of possible metallothionein (MT) nature occurring upon auranofin exposure of cultured human cells. An epithelial cell line (HE) and two sub-strains were examined. The HEAF sub-strain had been made resistant to 2 mumole auranofin/l culture medium. The resistance was associated with the appearance of gold-binding substances with gel filtration characteristics like MT. The HE100 sub-strain had been made resistant to 100 mumole CdCl2/l and contained high amounts of cytosolic Cd-induced MT. In addition, cultured synovial fibroblasts, derived from normal (SN) and rheumatoid (SRA) synovial tissues, were investigated. Evidence was obtained by RIA that the low molecular weight (mol.wt. 6000-7000) gold-binding proteins occurring in the HEAF cells and SRA cells following auranofin exposure, were of MT nature. The relative amounts of MT in the epithelial cell lines were: HE:HEAF:HE100 = 1:18:100. The relative amounts in the synovial fibroblasts were: SN:SRA:SRA treated with auranofin = 1:3:10. The HPLC methods used were found suitable for isolation of Cd-MT in the HE100 cells, but not for the Au-MT in the HEAF cells. By HPLC, the Cd-MT in the HE100 cells was resolved into 3 MT-1 and 1 MT-2 iso proteins exhibiting the amino acid composition typical of MT. Judged by HPLC, the MT in these cells constituted 0.4% of the cytosolic proteins. PMID- 3087368 TI - [Directions of alkylation of deoxyguanosine and deoxyguanylic acid by thio-TEPA]. AB - As exemplified with the reaction of well-known anticancer agent thio-TEPA with dGMP, the ability of ethylenimine derivatives to modify this DNA component under the conditions approaching the biological ones was demonstrated for the first time. Modification involves mainly the phosphate group alkylation. In addition, thio-TEPA alkylates the base in dGMP at position 7. The formation of dGMP 7-alkyl derivatives was confirmed by detecting the luminescent products generated in the course of this reaction. PMID- 3087369 TI - The striking association between lupus anticoagulant and fetal loss in systemic lupus erythematosus patients. PMID- 3087370 TI - Changes in bilirubin transport across the liver by the flavonoids (+)-cyanidanol 3 and palmitoyl-catechin. AB - The apparent maximal transport capacity (Tm) of the liver for bilirubin was studied in rats after oral treatment for two weeks with the two flavonoids (+) cyanidanol-3 and palmitoyl-catechin in order to investigate a possible mechanism of action on jaundice described in humans. (+)-Cyanidanol-3 produces no changes in bilirubin-Tm, and the analysis of bilirubin and its conjugates in the different compartments reveals a decreased amount of the whole bilirubin taken up by the liver. Palmitoyl-catechin, a more lipophilic derivative of catechin, produces a slight increase in bilirubin-Tm. This appears related to the increased conjugation rate demonstrated in vitro for bilirubin. A multicompartimental analysis shows a different distribution of bilirubins as compared to controls. It is likely that physicochemical changes of the membrane environment, where the enzyme is buried, have modified the capacity of the hepatocyte to dispose bilirubin. PMID- 3087371 TI - Effect of single and repeated treatment of chlordiazepoxide and sodium valproate on water intake in the rat and their influence on the antidipsogenic action of naloxone. AB - The action of single and repeated treatment with chlordiazepoxide (CDP) (5-10 mg/kg i.p.) and sodium valproate (VPA) (100-200 mg/kg i.p.) on water intake of rats adapted to a daily 23-h water deprivation schedule was investigated. The influence exerted by single or repeated treatment of the two drugs on the antidipsogenic effect of naloxone (Nx) (1 mg/kg s.c.) was studied too. Our results show that with single treatment of CDP the dipsogenic effect is lower and not further modified by increasing dose and by the time-course of the session; with repeated treatment the dipsogenic effect is greater and further enhanced by increasing dose and by the time-course of the session. Single or repeated treatment with VPA does not significantly affect the water intake. Single treatment of CDP enhances the antidipsogenic effect of Nx, while CDP, after repeated treatment, reverses the antidipsogenic effect of Nx. With VPA-Nx association, the response is univocal (antidipsogenic effect) independent of the experimental conditions. The results are briefly discussed. PMID- 3087372 TI - Inhibitory effect of disodium edetate on gastric secretion. AB - Disodium edetate (ethylenediaminetetraacetic acid, disodium salt; disodic EDTA), 3 g, was given, via an intravenous normal saline drip of 30 min, to 25 patients in order to assess a benefit for anaesthesia practice. A significant reduction of both volume and acidity of the gastric secretion was found in all the 10 patients with peptic ulcer having received the drug. The peak of the change was 1 h after administration. In other 10 non-ulcer patients undergoing orthopaedic surgeries under epidural anaesthesia with lidocaine 2%, 5 mg kg-1, pH of the gastric juice unanimously rose, from 2.24 +/- 0.28 to 4.10 +/- 0.21 1 h after EDTA with a P derived from paired difference analysis of less than 0.001. A similar group of patients receiving only normal saline showed no important changes in pH (from 2.37 +/- 0.24 to 2.34 +/- 0.19). The pH of the fundic surface, measured directly under fiberscopic control in further 5 patients suffering from peptic ulcer, was found also to rise from 1.84 +/- 0.21 to 4.62 +/- 0.34 1 h after EDTA, P less than 0.001. Total and ionized calcium changed unsignificantly. Disodic EDTA in the dose and manner used in this study showed no clinical side-effects. The constant and obvious effect of inhibition of the gastric secretion as well as the dynamics of such an action recommend disodic EDTA to be tried in reducing the aspiration pneumonia morbidity. PMID- 3087373 TI - The interactions of mesna and dimesna with the sulfate exchange in human red blood cells. AB - The influence of disodium 2-mercaptoethane sulfonate disulfide (mesna, Uromitexan) and sodium 2-mercaptoethane sulfonate (dimesna) on the carrier mediated exchange of 35S-sulfate in human red blood cells was investigated in vitro in order to contribute to the understanding of pharmakokinetics and organospecific action of mesna. Countertransport indicated uptake of mesna in washed red blood cells by the carrier. In contrast, dimesna inhibited the transport of sulfate in a competitive manner. However, when 35S-sulfate uptake into red cells was studied with whole blood, addition of mesna was found to be inhibitory, which was caused by its rapid conversion to dimesna by plasma components. It is concluded that conversion of the anion carrier substrate mesna into the inhibitor dimesna is the reason that mesna or dimesna cannot be detected in red blood cells in vivo. PMID- 3087374 TI - Studies of chemical and biologic properties of a fraction of sulodexide, a heparin-like glycosaminoglycan. AB - The chemical composition and biologic properties of a fraction (f) of Sulodexide, a heparin-like GAG, were studied and compared with those of two sulfated GAG preparations and heparin from intestinal mucosa. f-Sulodexide and the sulfated GAG preparations were fractionated on a Dowex-1Cl- column and subsequently on an antithrombin III affinity column. Low affinity and high affinity fractions had similar chemical composition and lipoprotein lipase releasing ability, but they varied in anticoagulant activity. Low affinity fractions from f-Sulodexide had negligible anticoagulant activity while high affinity fractions had one-half the activity of mucosal heparin. When compared to heparin, both fractions had one third amount of lipoprotein lipase releasing activity. The low anticoagulant activity of f-Sulodexide suggests a suitability for long-term use as an antiatherogenic agent. PMID- 3087375 TI - Degree of dependence on the ventilator according to sleep states in artificially ventilated premature infants. AB - Polygraphic recordings were performed in 14 sleeping premature infants receiving ventilation for respiratory distress syndrome. All were clinically stabilized, with normal EEG and neurologic status and differentiated sleep states (coded according to EEG and REM criteria). They all had two respiratory patterns: passive, completely dependent on the ventilator, and active, with autonomous respiratory movements and/or inspiratory diaphragmatic activity added to passive respiration. We found that in infants ventilated at the rate of 18-54/min, respiration was more active and autonomous in active REM sleep and more passive and dependent on the machine in quiet NREM sleep (P less than 0.005). Within the limits of the values observed in our study, differences between sleep states were not due to other factors that could possibly interfere with and modify the degree of respiratory autonomy. We found no significant correlation between the percentage of time passed with active respiration on one hand and age (gestational, postnatal, conceptional) or diagnostic or physical parameters of artificial ventilation and blood gas levels on the other hand. Our results suggest that in artificially ventilated but neurologically normal premature infants, differences between respiratory control in both sleep states exist as early as 28 weeks conceptional age (lower limit of our study). PMID- 3087376 TI - Medical care at the end of life: the interaction of economics and ethics. PMID- 3087377 TI - Electron microscopy of frozen, hydrated biological specimens. PMID- 3087378 TI - Teratogenic effects of lithium and ethanol in the developing fetus. AB - Prolonged administration of either lithium (7 mg/kg body wt.) or ethanol (30% of daily caloric intake) for 10 days to pregnant rats results in several anatomical abnormalities in the fetus. Intragastric administration of lithium carbonate to pregnant rats immediately after confirmation of pregnancy resulted in high incidence of cleft palate, growth retardation, brain liquification and pulpy brain, hepatomegaly and digital abnormalities, when compared to the saline treated controls. Furthermore, lithium administration during gestation also resulted in other less frequently observed abnormalities in the fetus, e.g., cardiomegaly, hydronephrosis, ankle-joint defects, syndactyly, defected ribs and sternum ossification defects. Chronic ethanol consumption by pregnant rats during early gestation also resulted in several anatomical abnormalities of prenatal growth retardation, resorption and still births, cleft palate, hydrocephaly and hydronephrosis. The severity and frequency of several of the fetal abnormalities were compounded when lithium and ethanol were administered simultaneously. The possible mechanisms of lithium and ethanol teratogenicity and their synergistic effects have been explained on a biochemical basis. PMID- 3087379 TI - Development of hepatic bilirubin glucuronidation as affected by prolonged maternal ethanol intake. AB - Prolonged maternal ethanol intake by lactating mothers resulted in a 26% and 41% decrease in serum conjugated bilirubin of 6 and 10 day old suckling newborn rats, respectively. An increase of 20% and 36% was observed in the serum unconjugated bilirubin levels in suckling newborns from the ethanol-fed group compared to the corresponding controls. Newborns suckling on ethanol-fed dams showed a small, but significant hyperbilirubinemia compared to the controls. Acute administration of ethanol (2.5 g/kg) to newborn rats also resulted in a decrease in serum conjugated bilirubin and an increase in the levels of unconjugated and total bilirubin. Prolonged ethanol intake by adults also resulted in a decrease in conjugated bilirubin and an increase in unconjugated and total bilirubin levels compared to the corresponding controls. Bilirubin glucuronide formation in the liver was decreased by ethanol by about 30% and 37% in the suckling newborn, and adults, respectively. Newborns suckling on ethanol-fed dams, as well as the dams consuming ethanol showed an increase in hepatic (UDPG)/(UDPGA) levels. The activity of hepatic bilirubin-UDP-glucuronyl transferase either in the newborns suckling on ethanol-fed dams, or in dams consuming ethanol chronically, was not significantly different from their corresponding controls. Ethanol was found to inhibit the glucuronidation of bilirubin by decreasing the availability of UDP glucuronic acid in the newborn and adult livers. PMID- 3087380 TI - Nicotine and carbon monoxide: effects on the isolated rat heart. AB - We studied the combined effects of carbon monoxide (CO) and nicotine on the performance of the isolated rat heart. Hearts were removed from laboratory rats and perfused through the aorta with 95% O2-5% CO2 (oxygenated) Krebs-Henseleit solution (KHs). After 30 min, the perfusate was switched rapidly to one of three solutions: KHs containing 10% CO-85% O2-5% CO2 (CO), 10 micrograms/ml nicotine (Nic), or CO combined with nicotine (CO + Nic). KHs containing CO increased coronary flow by 41% without affecting heart rate or pulse pressure. Coronary flow returned to control values during recovery in oxygenated KHs. KHs containing Nic decreased heart rate by 20% and coronary flow by 28%. Pulse pressure was unaffected. Both heart rate and coronary flow returned towards control values during recovery in oxygenated KHs. KHs containing CO + Nic decreased heart rate 16% but stimulated coronary flow 13%. Heart rate returned towards control values during recovery; however, coronary flow, which declined to control values after 8 min, continued to decrease during recovery. These results indicate that the separate effects of CO and Nic on coronary flow in the isolated rat heart are opposing and reversible, but that the decrease they produce in combination is irreversible. PMID- 3087381 TI - Pathologic quiz case 2. Scrofula (mycobacterial lymphadenitis). PMID- 3087382 TI - Flow kinetics of immobilized beta-glucosidase. AB - The enzyme beta-glucosidase was attached covalently to the inner surface of nylon tubing. Flow kinetic studies were carried out at a range of temperatures, pH values, flow rates, and substrate concentrations. Various tests showed that the extent of diffusion control was negligible. At 25 degrees C the Michaelis constant was 33.4 mM, not greatly different from the value for the enzyme in free solution. The pH dependence was similar to that for the free enzyme. The Arrhenius plots showed inflexions at about 22 degrees C, as with the free enzyme, the changes in slope being small at the pH optimum of about 5.9 and becoming much more pronounced as the pH is increased or decreased. The immobilized enzyme is more stable than the free enzyme, both on storage at low and higher temperatures, and its reuse stability is greater. PMID- 3087383 TI - A synthesis of N6,N6,N6-trimethyl-L-lysine dioxalate in gram amounts. AB - A procedure is described for the synthesis of crystalline N6,N6,N6-trimethyl-L lysine dioxalate in gram amounts starting from the commercially available N2-tert butoxycarbonyl-N6-benzyloxycarbonyl-L-lysine, which is reacted with methyl iodide in methanol in the presence of potassium hydrogen carbonate after deprotection of the side-chain amino group by catalytic hydrogenation. The work-up involves only filtrations and evaporations. PMID- 3087384 TI - Purification and properties of human placental NADPH-cytochrome P-450 reductase. AB - Human placental NADPH-cytochrome P-450 reductase (EC 1.6.2.4) was purified to electrophoretic homogeneity in two chromatographic steps with a high retention of bioactivity. After solubilization with 1% sodium cholate in a protective medium containing 20% glycerol, 10 microM 4-androstene-3,17-dione, 1 mM dithiothreitol, and 0.2 mM EDTA, a 35-60% ammonium sulfate precipitate was prepared. The crude protein mixture was then applied to a 2',5'-ADP-Sepharose 4B affinity column, followed by high-performance anion-exchange chromatography (Pharmacia Mono-Q column). Two forms of the reductase were isolated. One was eluted at higher salt concentration and had a relative mass (Mr) of 79 kdaltons (kDa) as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-performance gel permeation chromatography. A smaller size reductase with a Mr of 70 kDa, eluting at lower salt concentration, was also formed by trypsinolysis of the 79 kDa reductase. It must therefore be regarded as a proteolytic artifact. The absolute spectra in the visible region of the two reductases were identical with maxima at 376 and 452 nm, typical of a flavoprotein. They also had the same specific activity of 24.7 +/- 0.7 mumol/min per milligram protein towards cytochrome c. However, only the 79-kDa reductase showed aromatase-reconstitution activity. The homogeneity of these reductases was further confirmed by the appearance of a single peak when subjected to gradient, reversed-phase high performance liquid chromatography. According to its amino acid composition, the 79-kDa reductase is a highly acidic and hydrophobic protein, composed of 695 residues. PMID- 3087385 TI - Gastric proteases of the Greenland cod Gadus ogac. I. Isolation and kinetic properties. AB - The zymogens of three gastric proteases of the Greenland cod (Gadus ogac) were isolated by exclusion chromatography and chromatofocusing. The cod zymogens were activated more rapidly at lower temperatures than porcine pepsinogen and, after activation, were further purified by exclusion chromatography. The cod proteases had more alkaline pH optima and were active over a wider range of pH than porcine pepsin. The specific activity of porcine pepsin on protein substrates was greater than that of the individual cod proteases. However, the cod proteases had cumulative activity on protein substrates that was greater than the sum of their individual activities. Cod protease 1 was active on pepsin-specific substrates, and cod proteases 2 and 3 were active as gastricsin-specific substrates. All three cod proteases had greater milk-clotting activity and hydrolysed hemoglobin to a greater extent than porcine pepsin. The Vmax and Km,app of the cod proteases were dependent upon the substrate, and Vmax/Km,app values of the cod proteases were generally lower than porcine pepsin. It is suggested that the cod proteases together exhibit broad substrate specificity and maintain activity over a wide range of conditions to enhance protein digestion in the cod stomach. PMID- 3087386 TI - Acetylatable lipoic acid residues interact directly with lipoamide dehydrogenase in the pyruvate dehydrogenase multienzyme complex of Escherichia coli. AB - The proposal that the lipoate acetyltransferase component (E2) of the pyruvate dehydrogenase multienzyme (PD) complex from Escherichia coli contains three covalently bound lipoyl residues, one of which acts to pass reducing equivalents to lipoamide dehydrogenase (E3), has been tested. The PD complex was incubated with pyruvate and N-ethylmaleimide, to yield an inactive PD complex containing lipoyl groups on E2 with the S6 acetylated and the S8H irreversibly alkylated with N-ethylmaleimide. This chemically modified form would be expected to exist only on two of the three proposed lipoyl groups. The third nonacetylatable lipoyl group, which is proposed to interact with E3, would remain in its oxidized form. Reaction of the N-ethylmaleimide-modified PD complex with excess NADH should generate the reduced form of the proposed third nonacetylatable lipoyl group and thereby make it susceptible to cyclic dithioarsinite formation with bifunctional arsenicals (BrCH2CONHPhAsCl2; BrCH2[14C]CONHPhAsO). Once "anchored" to the reduced third lipoyl group via the--AsO moiety, these reagents would be delivered into the active site of E3 by the normal catalytic process of the PD complex where the BrCH2CONH--group inactivates E3. Whereas the E3 component of native PD complex is inactivated by the bifunctional reagents in the presence of excess NADH (owing to the above delivery process), the E3 component of the PD complex modified with N-ethylmaleimide in the presence of pyruvate is not inhibited. The results indicate that acetylatable lipoyl residues interact directly with E3 and do not support a functional role for a proposed third lipoyl residue. PMID- 3087387 TI - Light-induced interaction between rhodopsin and GTP-binding protein leads to the hydrolysis of GTP in the rod outer segment. AB - In the presence of exogenous GTP, vertebrate whole rod outer segments (ROS), with perforated plasma membranes in the "single particle" scattering range, elicit a light-induced light-scattering transient which we call the "G" signal. Here, we report on the characteristics of the "G" signal relative to the "binding" and "dissociation" signals reported by Kuhn and colleagues. Replacing GTP with guanylyl imidodiphosphate (GMP-PNP) does not give rise to the G signal. This indicates that hydrolysis of the terminal phosphate is required for the G signal and, in addition, GTP and GMP-PNP compete for the same binding site of the enzyme responsible for the G signal (i.e., GTP-binding protein). Also, neither GDP nor its nonhydrolyzable analogue, guanosine 5'-O-(2-thiodiphosphate), when present in ROS suspensions yield any light-scattering transient in the time period tested. PMID- 3087389 TI - Role of ornithine decarboxylase in proliferation of prolactin-dependent lymphoma cells. AB - Mitogenic stimulation of Nb2 lymphoma cells by lactogenic hormones (prolactin, human growth hormone) caused a dramatic early increase in ornithine decarboxylase (ODC) activity that achieved a maximal level by 6-8 h. A marked increase in ODC activity was also generated when cells which had reached a growth plateau were transferred to fresh medium that did not stimulate growth. Furthermore, low concentrations of human growth hormone (20 pg/mL) elicited a proliferative response, but did not cause a detectable early increase in ODC activity. The early peak of ODC activity thus appeared not to be directly involved in mediating lactogen-stimulated growth nor was it required to support the mitogenic response. However, prolonged suppression of ODC activity by DL-alpha difluoromethylornithine (DFMO) (200 microM) attenuated the growth of Nb2 cells (50-60% inhibition), indicating that normal cell growth was dependent on ODC and polyamine biosynthesis. Under these conditions, putrescine, the enzyme product, or the polyamines spermidine and spermine restored normal cell growth when added at a concentration of 1 microM or greater. Nb2-SP cells, variants which proliferate in the absence of prolactin, were about two times more resistant to the growth suppressive effects of DFMO than prolactin-responsive Nb2 cells. PMID- 3087388 TI - Effects of some inhibitors of DNA synthesis and repair upon the cycle of serotonin N-acetyltransferase activity in cultured chick pineal glands. AB - When chick pineal glands were cultured in the dark with aphidicolin from midphotoperiod, the increase of serotonin N-acetyltransferase (NAT) activity was stimulated and the time of peak NAT activity was advanced. The peak level of NAT activity was also reached sooner on the 2nd day of culture. The increase of NAT activity was also stimulated in glands cultured under diurnal illumination, but the time of peak activity was not advanced. Effects with glands explanted into culture in the dark at other times were smaller and the time of peak NAT activity was not changed. Cytosine arabinoside and dideoxythymidine also stimulated the increase of NAT activity and advanced the time of peak activity with glands cultured in the dark from midphotoperiod. 3-Aminobenzamide markedly stimulated the increase of NAT activity both in the dark and under diurnal lighting when pineal glands were explanted into culture at mid- or late photoperiod. In contrast, with glands in culture from earlier in the photoperiod, aminobenzamide had no effect upon the increase of NAT activity up to the peak level found with control glands. Thereafter results were variable. Effects of cordycepin upon development of NAT activity were similar to those of 3-aminobenzamide but less marked. Incorporation of thymidine into acid-insoluble material in the dark was very markedly inhibited by aphidicolin, cytosine arabinoside, and dideoxythymidine, but only slightly by cordycepin. Aminobenzamide strongly inhibited incorporation by glands cultured from midphotoperiod, but had little effect with glands in culture from near the end of the photoperiod. We adopt the working hypothesis that excision repair of DNA may be a major component in the mechanism of the chick pineal clock. PMID- 3087390 TI - Hormonal correlations in the polycystic ovary syndrome. PMID- 3087391 TI - [Nifedipine and stimulated secretion of prolactin in man]. PMID- 3087392 TI - Can serum bile acid determination substitute BSP loading test in detecting and monitoring chronic liver diseases? PMID- 3087393 TI - [Coexpression of differentiation antigens on circulating human T lymphocytes]. PMID- 3087395 TI - [A case of Fabry's disease without angiokeratoma: clinical, biochemical and electron microscopic study]. PMID- 3087394 TI - 14CO2 production is no adequate measure of [14C]fatty acid oxidation. AB - Palmitate oxidation was comparatively assayed in various cell-free and cellular systems by 14CO2 production and by the sum of 14CO2 and 14C-labeled acid-soluble products. The 14CO2 production rate was dependent on incubation time and amount of tissue in contrast to the total oxidation rate. The 14CO2 contribution to the oxidation rate of [1-14C]palmitate varied with homogenates from 1% with rat liver to 28% with rat kidney and amounted to only 2-4% with human muscles. With cellular systems the 14CO2 contribution varied between 20% in human fibroblasts and 70% in rat muscles and myocytes. Addition of cofactors increased the oxidation rate, but decreased the 14CO2 contribution. Various conditions appeared also to influence to a different extent the 14CO2 production and the total oxidation rate with rat tissue homogenates and with rat muscle mitochondria. Incorporation of radioactivity from [1-14C]palmitate into protein was not detectable in cell-free systems and only 2-3% of the sum of 14CO2 and 14C-labeled acid-soluble products in cellular systems. Assay of 14CO2 and 14C-labeled acid soluble products is a much more accurate and sensitive estimation of fatty acid oxidation than assay of only 14CO2. PMID- 3087396 TI - [Protective effect of phenytoin and its enhanced action by combined administration of mannitol and vitamin E in cerebral ischemia]. AB - Phenytoin is well known as the anticonvulsant agent and also said to protect the brain against ischemic damage. The purpose of the present experiment is to study the therapeutic effect of phenytoin on cerebral ischemia and confirm whether the effectiveness of phenytoin could be enhanced by combination of free radical scavengers such as mannitol and vitamin E. In this experiment, twenty-five dogs were subjected to ischemia, using the "canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump at will. Five animals served as untreated control, fifteen received treatment with phenytoin (7 mg/kg in five dogs, 10 mg/kg in five dogs and 30 mg/kg in five dogs) and five treated with 10 mg/kg phenytoin, 2 g/kg of mannitol and 30 mg/kg of vitamin E. These drugs were administered intravenously 20 minutes prior to the production of ischemia, when cerebral blood flow was reduced to one-tenth its normal volume. After one hour, cerebral blood flow was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. With regard to the recovery of EEG, no recovery of EEG was seen subsequent to recirculation except one dog in the control group. Whereas in the group treated with phenytoin, gradual emergence of slow wave ws observed soon after recirculation. The higher the administered dosage is, the better the degree of recovery of EEG was seen. Thus, the dose-related recovery of EEG was observed within the dose ranges tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087397 TI - The label escape error: comparison of measured and theoretical fraction of total bone-trabecular surface covered by single label in normals and patients with osteoporosis. AB - Thirty-four normal Caucasian women and 69 patients with osteoporosis were given two bone-labeling agents. Transilial biopsies were obtained and embedded undecalcified. Fractional surfaces covered by double label and single label were determined, along with total surface and double label width by fluorescent microscopy. Mean wall thickness was measured on toluidine blue-stained sections. The mathematical model for predicting the amount of single-labeled surface was compared to the actual amount of surface covered by single label. We found an excess of single labels compared to the model in both groups, more so in the normals, and suggest the explanation is that bone-formation pauses at formation sites in both groups but tends not to resume in the patients. This results in a shortened functional life span of the osteoblast and bone loss. Further, the data suggest that for accurate expression of bone formation rates in trabecular bone using a volume referent, one should use the whole bone tissue including bone and marrow and should express the bone-forming surface as the double-labeled surface plus one-half the measured single-labeled surface. PMID- 3087399 TI - Low central nervous system penetration of N2,N4,N6,-trihydroxymethyl-N2,N4,N6, trimethylmelamine (Trimelamol): a cytotoxic s-triazine with reduced neurotoxicity. AB - Trimelamol (N2,N4,N6-trihydroxymethyl-N2,N4,N6-trimethylmelamine) is an analogue of pentamethylmelamine (PMM). In early clinical trials PMM failed to show significant anti-tumour activity in man which was attributed to poor metabolic activation. Trimelamol does not require activation and is therefore expected to be more active in man. PMM caused dose-limiting emesis and sedation whereas Trimelamol is much less neurotoxic in rodents. The relative penetration of PMM and Trimelamol into mouse brain has therefore been examined. Mice receiving PMM at 90 mg kg-1 i.p. were found to have high concentrations of the drug in the CNS compared to plasma (mean brain/plasma ratio 1.04) whereas animals receiving Trimelamol had consistently low CNS concentrations (mean brain/plasma ratio 0.08). This difference did not correlate with plasma protein binding which is greater for PMM (68.2%) than for Trimelamol (17.5%). However, it does appear to be related to lipophilicity. In Phase I clinical trial Trimelamol has proved much less emetic than PMM and causes no acute sedation. It is likely that this reduction in toxicity may be explained by the relatively poor ability of Trimelamol to enter the CNS. PMID- 3087398 TI - Domperidone treatment in man inhibits the fall in plasma renin activity induced by intravenous gamma-L-glutamyl-L-dopa. AB - The dopamine pro-drug gamma-L-glutamyl-L-dopa (gludopa) was administered intravenously to six normal subjects at a dose of 12.5 micrograms min-1 kg-1, either with or without the dopamine antagonist domperidone. A control was provided by the intravenous infusion of domperidone and saline on a separate occasion. Intravenous gludopa produced a significant natriuresis, whether administered alone or in combination with domperidone. After gludopa infusion, there was a significant fall in plasma renin activity, an effect which was attenuated significantly by concomitant treatment with domperidone. These observations suggest that blockade of renal DA2 dopamine receptors has little or no effect on gludopa-induced natriuresis, but that at least part of the dopaminergic inhibition of renin release is mediated by renal DA2 receptors. PMID- 3087400 TI - Serum androgen binding protein and follicle stimulating hormone as indices of Sertoli cell function in the irradiated testis. PMID- 3087401 TI - Precipitation of latent renal radiation injury by unilateral nephrectomy. PMID- 3087402 TI - The relationship between functional assays of radiation response in the lung and target cell depletion. PMID- 3087404 TI - Cutaneous schistosomiasis in Nigeria. An update. AB - Two patients with schistosomiasis of the skin were seen at the Ahmadu Bello University Teaching Hospital, Kaduna, Northern Nigeria, between June 1978 and December 1980. The first case was not suspected on clinical grounds, but was diagnosed only after terminally-spined ova of Schistosoma haematobium were found in histological sections of the skin lesions. Both patients were successfully treated with niridazole (Ambilhar). These bring to eight the total number of cases of cutaneous schistosomiasis recorded in Nigeria in the past 40 years, four of which were in indigenous Nigerians. It seems that the high endemicity of the disease confers some degree of natural immunity to the indigenous population, making ectopic forms rare. Clinicians should be aware of the existence of cutaneous forms of the disease and of their excellent response to specific chemotherapy. PMID- 3087403 TI - Arachidonic acid metabolism by peripheral blood cells in psoriasis. AB - The metabolism of arachidonic acid by mixed suspensions of leukocytes and platelets prepared from peripheral blood has been studied in 20 patients with psoriasis and 21 healthy controls. A lipoxygenase-derived product, identified as 12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid was formed in increased amounts by the cell suspension from the psoriatic patients. This product results from the metabolism of platelet-derived 12-hydroxy-5,8,10,14-eicosatetraenoic acid by the polymorphonuclear leukocyte 20-hydroxylase enzyme. By contrast, synthesis of the cyclo-oxygenase products 12-hydroxy-5,8,10-heptadecatrienoic acid and thromboxane B2 was diminished. Benoxaprofen, which is known to be beneficial in psoriasis, diminished the levels of 12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid formed in vitro. PMID- 3087405 TI - Expectations of human epidermal kinetic homeostasis. PMID- 3087406 TI - Red cell alloimmunization in sickle cell disease. AB - Alloimmunization to red cell antigens contributes to morbidity in transfused patients. It has been recommended that blood for sickle cell patients need not be matched for antigens other than ABO and Rh(D), as there is no greater incidence of antibody production than in other multitransfused patient populations. Post transfusion alloimmunization was studied in a group of 34 sickle cell disease patients attending a U.K. haemoglobinopathy clinic. Red cell antibodies were formed in 17.6% of the transfused patients and Rhesus and Kell antibodies accounted for 66% of this total. In order to reduce alloimmunization, a policy of performing extended red cell phenotyping on the patients, and providing blood matched for Kell, and in certain circumstances the Rhesus antigens other than Rh(D), is recommended. PMID- 3087407 TI - A pathway of coagulation on bovine capillary endothelial cells. AB - In this report cultured bovine capillary endothelial cells are demonstrated to specifically bind factors IX and X and also their activated forms. Bound factor IXa and cell-associated factor VIII can activate factor X. The product of this reaction, factor Xa, can then interact with a factor V-like molecule expressed by capillary endothelial cells promoting thrombin formation. The thrombin formed can cleave fibrinogen leading to release of fibrinopeptide A and clot formation. Endotoxin-treatment of capillary endothelial cells leads to induction of tissue factor activity which, in the presence of factor VIIa, promotes activation of factors IX and X. The amount of factor Xa formed endotoxin-treated endothelial cells incubated with factors VIIa, IX, VIII and X, is 8 times greater than cells incubated with factors VIIa and X alone. This indicates that on the perturbed endothelial cell surface factors VIII and IX do play an important role in factor X activation by the tissue factor pathway. The perturbed capillary endothelial cell can thus provide a model of the thrombotic state promoting initiation and propagation of a procoagulant pathway leading to thrombin formation. This pathway of coagulation is endothelial cell-dependent, since it requires expression of tissue factor and factor V by capillary endothelial cells, as well as interaction of coagulation factors with the surface of capillary endothelial cells. PMID- 3087409 TI - Experimental contamination of Minims of fluorescein by Pseudomonas aeruginosa. AB - Contamination of fluorescein solutions by Pseudomonas aeruginosa has been a concern of ophthalmologists for many years because of the severity of pseudomonas keratitis. Attempts to prevent contamination have been directed at stringent sterility control during manufacture and the introduction of single-dose disposable containers such as Minims. Deliberate contamination of Minims fluorescein with Pseudomonas aeruginosa was attempted. Under conditions likely to be met with in clinical practice the contents remained sterile. However, under extreme conditions of immersion in pure broth culture of Pseudomonas aeruginosa contamination could be achieved. The relevance of these results to clinical practice is discussed. PMID- 3087408 TI - Immunoglobulin chain gene rearrangements in a t(4;11) acute leukaemia with monocytoid blasts. AB - We report a case of acute leukaemia with the t(4;11) chromosomal translocation which, at initial diagnosis, had L-1 lymphoblasts that were positive for terminal deoxynucleotidyl transferase (TdT) and HLA-DR but negative for myeloid cytochemical markers. At last relapse the patient had mostly monocytoid blasts which were not TdT negative but were positive for HLA-DR, weakly positive for Sudan Black B (SB), periodic acid Schiff's (PAS), naphthol AS-D acetate esterase (NSE), chloroacetate esterase (CAE) and negative for acid phosphatase (AP) and nitroblue tetrazolium (NBT) reduction. Treatment with 12-o-tetradecanoylphorbol 13-acetate (TPA) in vitro induced differentiation to macrophage-like cells that were strongly positive for SB, PAS, NSE, AP, CAE and NBT reduction, indicating a latent monocyte-like phenotype. Thus the leukaemic cell clone or a precursor clone with the t(4;11) translocation manifested a lymphoid phenotype at initial diagnosis and a monocytoid phenotype at relapse. Immunoglobulin gene analysis of the monocytoid relapse blasts revealed rearrangements of the heavy chain gene alleles and germline light chain genes. Thus, the leukaemia clone with the t(4;11) chromosomal translocation could be a bipotential cell with heavy chain gene rearrangements occurring in a primitive cell which may retain the ability to differentiate along the myeloid-monocytoid lineage in response to the appropriate stimulus. Alternatively, these characteristics may result from a transformation associated event. PMID- 3087410 TI - Conformation and stability of the constant fragment of the immunoglobulin light chain containing an intramolecular mercury bridge. AB - The constant fragment of the immunoglobulin light chain in which the intramolecular disulfide bond is reduced (reduced CL fragment) assumes a conformation very similar to that of the intact CL fragment and contains two sulfhydryl groups buried in the interior of the molecule [Goto, Y., & Hamaguchi, K. (1979) J. Biochem. (Tokyo) 86, 1433-1441]. In order to understand the role of the disulfide bond, a derivative in which the disulfide bond is replaced by an S Hg-S bond was prepared and its conformation and stability were studied. The derivative was prepared by reacting the reduced CL fragment with mercuric chloride. Kinetic studies showed that the reaction is rate-limited by the unfolding process of the reduced CL fragment. The mercury derivative was as compact as the intact CL or reduced CL fragment, and a tryptophyl residue was found to be buried near the S-Hg-S bond in the interior of the protein molecule. Judging from the circular dichroic spectrum, however, the beta-structure characteristic of the immunoglobulin fold was disturbed. The stability of the derivative to guanidine hydrochloride was lower than that of the intact CL fragment, but the unfolding transition was reversible and cooperative. Decreased stability of the mercury derivative is due to its folded conformation being distorted by introduction of the S-Hg-S bond. PMID- 3087411 TI - A novel disialoganglioside (IV3NeuAcIII6NeuAcLc4) of human adenocarcinoma and the monoclonal antibody (FH9) defining this disialosyl structure. AB - This ganglioside is highly immunogenic, and immunization of mice with this disialoganglioside fraction coated on Salmonella minnesota followed by fusion of immunized spleen cells with mouse myeloma and selection of the hybridoma by positive reactivity with the purified disialoganglioside resulted in the establishment of a hybridoma secreting immunoglobulin G2a antibody FH9 that reacts specifically with the ganglioside antigen above but not with monosialosyllactotetraosylceramide I (IV3NeuAcLc4), monosialosyllactotetraosylceramide II (III6NeuAcLc4), or any other gangliosides tested. PMID- 3087412 TI - Biochemical characterization of the phospholipase A2 purified from the venom of the Mexican beaded lizard (Heloderma horridum horridum Wiegmann). AB - A phospholipase A2 was isolated from the venom of the mexican beaded lizard (Heloderma horridum horridum) by phenyl-Sepharose chromatography followed by Sephadex G-75 gel filtration and two additional steps on ion exchange resins (DE 32 cellulose). The affinity chromatographic method (PC-Sepharose 4B) reported for the isolation of other phospholipases [Rock, Ch. O., & Snyder, F. (1975) J. Biol. Chem. 250, 2564-2566; King, T. P., Alagon, A. C., Kwan, J., Sobotka, A. K., & Lichteinstein, L. M. (1983) Mol. Immunol. 20, 297-308; King, T. P., Kochoumian, L., & Joslyn, A. (1984) Arch. Biochem. Biophys. 230, 1-12] was uneffective for the separation of this enzyme. The monomeric form of the Heloderma phospholipase has an apparent Mr of 18 000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 19 060 as calculated from amino acid analysis. It also contains on the order of 7% carbohydrates per mole of enzyme. The N-terminal amino acid sequence was shown to be very different from that of phospholipases isolated from mammalian pancreas and crotalids and elapids snake venoms. The first 39 amino acid residues at the N-terminal region have 56% homology with bee venom phospholipase but differ from the bee phospholipase in that its isoelectric point is acidic (pI = 4.5), instead of basic, and it has approximately 50 amino acid residues more in the molecule. The specificity of the enzyme is mainly A2 type with possible residual B-type activity. The enzymatic activity is Ca2+ dependent. Half-cystine alignment of the Heloderma phospholipase sequence with those of other known phospholipases shows the lack of an octadecapeptide at the N terminal region, the existence of an extra hexapeptide at positions 42-47, and an exact correspondence of Heloderma Gly-12, Gly-14, His-36, and Asp-37 with Gly-30, Gly-32, His-48, and Asp-49 from other phospholipases shown to be important for Ca2+ binding (( Dijkstra, B. W., Drenth, J., Kalk, K. H., & Vandermaalen, P. J. (1978) J. Mol. Biol. 124, 53-60 )).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087413 TI - Inhibition of Euglena gracilis and wheat germ zinc RNA polymerases II by 1,10 phenanthroline acting as a chelating agent. AB - Copper complexes of 1,10-phenanthroline (OP-Cu) hydrolyze DNA [D'Aurora, V., Stern, A. M., & Sigman, D. S. (1978) Biochem. Biophys. Res. Commun. 80, 1025 1032; Marshall Pope, L., Reich, K. A., Graham, D. R., & Sigman, D. S. (1982) J. Biol. Chem. 257, 12121-12128]. This reaction has been studied to determine whether the 1,10-phenanthroline (OP) inhibition of the activity of RNA and DNA polymerases is the result of template hydrolysis or the chelation of a metal associated with and essential to the function of these enzymes. Addition of 4',6 diamino-2-phenylindole dihydrochloride (DAPI) to DNA generates a fluorescence signal with a linear increase of the intensity over a broad range of DNA concentrations from 0 to 100 micrograms/mL. The progress of hydrolysis of DNA by DNase I or OP (2 mM) is monitored by the time-dependent decrease in DAPI-induced fluorescence. In the presence of OP, the rate of hydrolysis increases as the Cu2+ concentration in the reaction mixture rises from 10(-8) to 10(-5) M. The rate differs for each nucleic acid template used; hydrolysis of poly(dA-dT) greater than denatured DNA greater than double-stranded DNA. However, millimolar amounts of OP do not hydrolyze the template even in the presence of Cu2+ (10(-6) M) when DNA is complexed with either Escherichia coli DNA polymerase I or Euglena gracilis or wheat germ RNA polymerase II. Under the same conditions, OP inhibits the activity of both varieties of RNA polymerase II with pKi's of 3.4 and 3.0, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087414 TI - Identification of three G.U base pairs in Bacillus subtilis ribosomal 5S RNA via 500-MHz proton homonuclear Overhauser enhancements. AB - Three distinct G.U base pairs in Bacillus subtilis 5S RNA have been identified via homonuclear Overhauser enhancements (NOE) of their low-field (9-15 ppm) proton Fourier transform nuclear magnetic resonances at 11.75 T. With these G.U resonances as starting points, short segments of NOE connectivity can be established. One G.U-G.C-G.C segment (most probably G4.C112-G5.C111-U6.G110) can definitely be assigned to the terminal helix. The existence of at least part of the terminal helical stem of the secondary structure of a Gram-positive bacterial 5S RNA has thus been established for the first time by direct experimental observation. Addition of Mg2+ produces almost no conformational changes in the terminal stem but results in major conformational changes elsewhere in the structure, as reflected by changes in the 1H 500-MHz low-field NMR spectrum. Assignment of the two remaining G.U base pairs will require further experiments (e.g., enzymatic-cleavage fragments). Finally, the implications of these results for analysis of RNA secondary structure are discussed. PMID- 3087416 TI - Localization of virginiamycin S binding site on bacterial ribosome by fluorescence energy transfer. AB - Virginiamycin S, a type B synergimycin inhibiting protein synthesis in bacteria, competes with erythromycin for binding to the 50S ribosomal subunits; the mechanism of action of the two antibiotics is unclear. Energy-transfer experiments between virginiamycin S (which is endowed with inherent fluorescence due to its hydroxypicolinyl moiety) and fluorescent coumarinyl derivatives of ribosomal proteins L7 and L10 have been carried out to locate the binding site of this antibiotic on the ribosome. Previous studies have indicated that two L7/L12 dimers can attach respectively to a strong binding site located on the central protuberance and to a weak binding site located on the stalk of the 50S subunits and that protein L10 is located at the base of the stalk. The distance between ribosome-bound virginiamycin S and a fluorophore located at the strong binding site of proteins L7/L12 (Lys-51 of L7) was found to be 56 (+/- 15) A. Virginiamycin S, on the other hand, was located at a distance exceeding 67 A from the weak binding site of L7/L12 dimers. A fluorophore positioned on the unique cysteine (Cys-70) of protein L10 and ribosome-bound virginiamycin S proved to be more than 60 A apart. From data available on the location of proteins L7/L12 and L10, a model is proposed, whereby the virginiamycin S binding site is placed at the base of the central protuberance of the 50S subunits, in proximity of the presumptive peptidyl transferase center. The binding sites of macrolides and lincosamides (related antibiotics of the MLS group) are expected to be very close to that of virginiamycin S. PMID- 3087415 TI - Clustering of phosphorylated amino acid residues in neurofilament proteins as revealed by 31P NMR. AB - The state of phosphorylation in neurofilament (NF) proteins is studied by the 31P NMR technique. The 31P NMR spectrum of intact NF proteins at pH 7.0 is comprised of a major resonance at 4.18 ppm and a minor resonance at 3.53 ppm. The chemical shifts of the major and minor resonances are strongly dependent on pH and have pKa values for phosphoserine of 5.85 and for phosphothreonine of 6.00, respectively. 31P NMR spectra of isolated NF polypeptides show nonequivalent phosphoserine clusters in NF150 and in NF200. Their chemical shifts are very similar in both polypeptides, but the intensities of homologous resonances are different. NF68 has no detectable 31P resonance signal. Phosphate-specific monoclonal antibodies to NF200 can distinguish phosphates of various clusters. Microtubule proteins can also produce specific alteration of the 31P resonances of NF200. NF proteins digested by calcium-activated neutral protease (CANP) show relatively little change in 31P resonances. PMID- 3087417 TI - Identification and assignment of base pairs in the "tuned helix" of intact and ribonuclease T1 cleavage fragments of wheat germ ribosomal 5S RNA via 500-MHz proton homonuclear Overhauser enhancements. AB - Wheat germ has been chosen as a representative eukaryote for study of ribosomal 5S RNA secondary structure. Proton homonuclear Overhauser enhancements (NOE's) at 500 MHz for the hydrogen-bonded base-pair protons in the 10-15 ppm region are used to establish the identity (A X U, G X C, or G X U) and base-pair sequence (e.g., G X C-A X U-C X G) within a given helical segment. Assignment of that segment to particular base pairs in the secondary structure is based upon NOE's conducted at different temperatures (to determine which signals "melt" together), variation of salt conditions (to produce differential chemical shifts in order to better distinguish components of an unresolved spectral envelope), and isolation and purification of RNase T1 cleavage fragments (in order to reduce the spectrum to just a few base pairs). The NOE patterns for the RNase T1 fragments are the same as in the intact 5S RNA, supporting the assumption that structural features of this region in the intact 5S RNA are preserved in the fragment. Chemical shifts predicted from ring current induced effects for a proposed base-pair sequence are then compared to experimental chemical shifts. By these methods, a portion of the "tuned helix" segment (namely, the base-pair sequence C18G60 A19U59-C20G58) is demonstrated spectroscopically for the first time in any 5S RNA. The tuned helix and common arm segments are less stable than the rest of the molecule. Variation of sodium and magnesium levels reveals multiple configurations of the wheat germ 5S RNA in solution. PMID- 3087418 TI - Histidinoalanine, a naturally occurring cross-link derived from phosphoserine and histidine residues in mineral-binding phosphoproteins. AB - Native mineral-containing phosphoprotein particles were isolated from the Heterodont bivalve Macrocallista nimbosa. The native particles are discrete structures about 40 nm in diameter which migrate as a single band during electrophoresis in agarose gels. Removal of the mineral component with ethylenediaminetetraacetic acid dissociates the native protein into nonidentical subunits. The lower molecular weight subunits, representing 8% of the total protein, were obtained by differential centrifugation. The native protein is characterized by a high content of aspartic acid, phosphoserine, phosphothreonine, histidine, and the bifunctional cross-linking residue histidinoalanine. The low molecular weight subunits have the same amino acid composition except for a reduction in histidinoalanine and a corresponding increase in phosphoserine and histidine residues, demonstrating that the alanine portion of the cross-link is derived from phosphoserine residues. Ion-exchange chromatography and molecular sieve chromatography show that the low molecular weight subunits have a similar charge density but differ in molecular weight, and the relative mobilities of the subunits on agarose gels indicate that they are polymers of a single phosphoprotein molecule. The minimum molecular weight of the monomer is about 140 000 on the basis of the amino acid composition. The high molecular weight subunits are rich in histidinoalanine and too large to be resolved by either molecular sieve chromatography or gel electrophoresis. On the basis of the ultrastructural, electrophoretic, chromatographic, and compositional evidence, native phosphoprotein particles are composed of subunits ionically cross-linked via divalent cations. These subunits are variable molecular weight aggregates of a single phosphoprotein molecule covalently cross-linked via histidinoalanine residues. Evidence for a nonenzymatic cross-linking mechanism is discussed. PMID- 3087419 TI - Studies of thermally induced denaturation of azurin and azurin derivatives by differential scanning calorimetry: evidence for copper selectivity. AB - Azurin, a blue copper protein from Pseudomonas aeruginosa, and several derivatives of azurin have been studied by differential scanning calorimetry. Two well-separated, irreversible transitions are observed in a scan of apoazurin under a variety of conditions, and they are assigned to distinct steps in the denaturation process. No specific structural component can be assigned to the lower temperature transition, but a "flap" structure which is found near the metal binding site may be involved. Circular dichroic spectra suggest that melting of the beta-sheet structure, the main structural motif in the native protein, occurs during the second transition. With the exceptions of the Ni(II) and p-(hydroxymercuri)benzoate derivatives, the transitions are superposed in the metalated forms, and the enthalpies of denaturation are more endothermic. By comparison with other first-row divalent transition ions and especially Zn(II), the Cu(II) derivative exhibits the most endothermic denaturation process. Along with other data, this suggests that the binding energy is greater for Cu(II). It is postulated that the selectivity for copper over zinc arises because of the irregular binding geometry offered by the folded protein. Denaturation of the Hg(II) derivative is even more endothermic, confirming that the type 1 binding site has a very great affinity for Hg(II). Finally, when substoichiometric amounts of Hg(II) are added to the apoprotein, there is evidence that a novel mercury-bridged dimer of azurin forms. PMID- 3087420 TI - Characterization of the reaction of L-serine and indole with Escherichia coli tryptophan synthase via rapid-scanning ultraviolet-visible spectroscopy. AB - The pre-steady-state reaction of indole and L-serine with the alpha 2 beta 2 complex of Escherichia coli tryptophan synthase has been investigated under different premixing conditions with rapid-scanning stopped-flow (RSSF) UV-visible spectroscopy for the spectral range 300-550 nm. When alpha 2 beta 2 was mixed with indole and L-serine, the reaction of alpha 2 beta 2 was found to occur in three detectable relaxations (1/tau 1 greater than 1/tau 2 greater than 1/tau 3) with rate constants identical with the three relaxations seen in the partial reaction with L-serine [Drewe, W.F., Jr., & Dunn, M.F. (1985) Biochemistry 24, 3977-3987]. Kinetic isotope effects due to substitution of 2H for the alpha-1H of serine were found to be similar to the effects observed in the reaction with serine only. The observed spectral changes and isotope effects indicate that the aldimine of L-serine and PLP and the first quinoid derived from this external aldimine are transient species that accumulate during tau 1. Conversion of these intermediates to the alpha-aminoacrylate Schiff base during tau 2 and tau 3 limits the rate of formation of the second quinoidal species (lambda max 476 nm) generated via C-C bond formation between indole and the alpha-aminoacrylate intermediate. The pre-steady-state reaction of the alpha 2 beta 2-serine mixture with indole is comprised of four relaxations (1/tau 1* greater than 1/tau 2* greater than 1/tau 3* greater than 1/tau 4*).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087421 TI - Beta-glucosidase: substrate, solvent, and viscosity variation as probes of the rate-limiting steps. AB - The second-order rate constants (kcat/Km) for the beta-glucosidase-catalyzed hydrolysis of aryl beta-D-glucopyranosides show a bell-shaped dependence of pH. The pKas that characterize this dependence are 4.4 (delta Hion approximately equal to 0) and 6.7 (delta Hion approximately equal to 0). In D2O these pKas are increased by 0.5 (+/- 0.1) unit, but there is no solvent isotope effect on the pH independent second-order rate constant. Nath and Rydon [Nath, R. L., & Rydon, H. N. (1954) Biochem. J. 57, 1-10] examined the kinetics of the beta-glucosidase catalyzed hydrolysis of a series of substituted phenyl glucosides. We have extended this study to include glucosides with phenol leaving groups of pKa less than 7. Bronsted plots for this extended series were nonlinear for both kcat/Km and kcat. Bronsted coefficients for those compounds with leaving groups of pKa greater than 7 (for kcat/Km) or pKa greater than 8.5 (for kcat) were nearly equal to -1.0, indicating substantial negative charge buildup on the leaving group in the transition state. The nonlinearity indicates an intermediate in the reaction. This was confirmed by partitioning experiments in the presence of methanol as a competing glucose acceptor. A constant product ratio, [methyl glucoside]/[glucose], was found with aryl glucoside substrates varying over 16,000-fold in reactivity (V/K), indicative of a common intermediate. Viscosity variation (in sucrose-containing buffers) was used to probe the extent to which the beta-glucosidase reactions are diffusion-controlled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087422 TI - Nanosecond fluorescence from chromatophores of Rhodopseudomonas sphaeroides and Rhodospirillum rubrum. AB - Single-photon counting techniques were used to measure the fluorescence decay from Rhodopseudomonas sphaeroides and Rhodospirillum rubrum chromatophores after excitation with a 25-ps, 600-nm laser pulse. Electron transfer was blocked beyond the initial radical-pair state (PF) by chemical reduction of the quinone that serves as the next electron acceptor. Under these conditions, the fluorescence decays with multiphasic kinetics and at least three exponential decay components are required to describe the delayed fluorescence. Weak magnetic fields cause a small increase in the decay time of the longest component. The components of the delayed fluorescence are similar to those found previously with isolated reaction centers. We interpret the multi-exponential decay in terms of two small (0.01 0.02 eV) relaxations in the free energy of PF, as suggested previously for reaction centers. From the initial amplitudes of the delayed fluorescence, it is possible to calculate the standard free-energy difference between the earliest resolved form of PF and the excited singlet state of the antenna complexes in R. rubrum strains S1 and G9. The free-energy gap is found to be about 0.10 eV. It also is possible to calculate the standard free-energy difference between PF and the excited singlet state of the reaction center bacteriochlorophyll dimer (P). Values of 0.17 to 0.19 eV were found in both R. rubrum strains and also in Rps. sphaeroides strain 2.4.1. This free-energy gap agrees well with the standard free energy difference between PF and P determined previously for reaction centers isolated from Rps. sphaeroides strain R26. The temperature dependence of the delayed fluorescence amplitudes between 180 K and 295 K is qualitatively different in isolated reaction centers and chromatophores. However, the temperature dependence of the calculated standard free-energy difference between P* and PF is similar in reaction centers and chromatophores of Rps. sphaeroides. The different temperature dependence of the fluorescence amplitudes in reaction centers and chromatophores arises because the free-energy difference between P* and the excited antenna is dominated by the entropy change associated with delocalization of the excitation in the antenna. We conclude that the state PF is similar in isolated reaction centers and in the intact photosynthetic membrane. Chromatophores from Rps. sphaeroides strain R-26 exhibit an anomalous fluorescence component that could reflect heterogeneity in their antenna. PMID- 3087423 TI - Basolateral amino acid transport systems in the perfused exocrine pancreas: sodium-dependency and kinetic interactions between influx and efflux mechanisms. AB - Basolateral amino acid transport systems have been characterized in the perfused exocrine pancreas using a high-resolution paired-tracer dilution technique. Significant epithelial uptakes were measured for L-alanine, L-serine, alpha methylaminoisobutyric acid, glycine, methionine, leucine, phenylalanine, tyrosine and L-arginine, whereas L-tryptophan and L-aspartate had low uptakes. alpha Methylaminoisobutyric acid transport was highly sodium dependent (81 +/- 3%), while uptake of L-serine, L-leucine and L-phenylalanine was relatively insensitive to perfusion with a sodium-free solution. Cross-inhibition experiments of L-alanine and L-phenylalanine transport by twelve unlabelled amino acids indicated overlapping specificities. Unidirectional L-phenylalanine transport was saturable (Kt = 16 +/- 1 mM, Vmax = 12.3 +/- 0.4 mumol/min per g), and weighted non-linear regression analysis indicated that influx was best described by a single Michaelis-Menten equation. The Vmax/Kt ratio (0.75) for L phenylalanine remained unchanged in the presence of 10 mM L-serine. Although extremely difficult to fit, L-serine transport appeared to be mediated by two saturable carriers (Kt1 = 5.2 mM, Vmax1 = 7.56 mumol/min per g; Kt2 = 32.8 mM, Vmax2 = 22.9 mumol/min per g). In the presence of 10 mM L-phenylalanine the Vmax/Kt ratio for the two L-serine carriers was reduced, respectively, by 79% and 50%. Efflux of transported L-[3H]phenylalanine or L-[3H]serine was accelerated by increasing perfusate concentrations of, respectively, L-phenylalanine and L serine, and trans-stimulated by other amino acids. In the pancreas neutral amino acid transport appears to be mediated by Na+-dependent Systems A and ASC, the classical Na+-independent System L and another Na+-independent System asc recently identified in erythrocytes. The interactions in amino acid influx and efflux may provide one of the mechanisms by which the supply of extracellular amino acids for pancreatic protein synthesis is regulated. PMID- 3087424 TI - Lipid bilayer dynamics in plasma and coated vesicle membranes from bovine adrenal cortex. Evidence of two types of coated vesicle involved in the LDL receptor traffic. AB - Pure coated vesicles have been prepared from the bovine adrenal cortex and two homogeneous populations have been separated, one of large diameter (100 nm) and one of small diameter (70 nm). The chemical composition in lipids and proteins of coated vesicles has been compared with that of partially purified plasma membranes and evidences a higher protein/lipid ratio and a higher concentration in phosphatidylethanolamine and unsaturated fatty acids. Evaluation of the lateral diffusion of pyrene in the lipid bilayer of coated vesicles as compared to uncoated vesicles evidences a slowing-down effect of clathrin. Measurements of lipids' rotational diffusion by time-resolved fluorescence indicate a decrease in the order parameter of the lipids in the coated vesicles due to clathrin. A hypothesis is proposed for a possible role of the clathrin coat in the concerted motion of lipids and proteins toward coated pits and in the mechanism of formation of coated vesicles. Separation of the large from the small coated vesicles made it possible to reveal different protein components in the two types of vesicle by electrophoresis and autoradiograms of the [gamma-32P]adenosine triphosphate- (ATP-) treated vesicles. Visualisation of the low-density lipoprotein receptor by ligand blotting and enzyme-linked immunosorbent assay (ELISA) techniques indicates an increased low-density lipoprotein receptor binding capacity in small coated vesicles as compared to large ones and plasma membranes. PMID- 3087425 TI - Selective insolubility of active hsp70 gene chromatin. AB - A gentle chromatin fractionation procedure was used to investigate solubility properties of Drosophila hsp70 heat-shock genes. After a brief digestion of isolated nuclei with micrococcal nuclease, most DNA is readily solubilized under low-ionic-strength conditions that maintain native nucleosomal organization. Actively transcribing hsp70 genes, however, are found to be enriched in the insoluble nuclear residue. Inactive genes are not resistant to solubilization, showing a fractionation pattern similar to that of bulk DNA. The insolubility characteristic correlates well with two other structural features of active hsp70 chromatin: increased sensitivity to endonuclease attack and disruption of the nucleosomal repeat pattern. The 5'-flanking regulatory region of active hsp70 genes is particularly resistant to solubilization, suggesting a role for binding of transcription factors in mediating this effect. PMID- 3087427 TI - beta-Glucosidase inhibition in murine peritoneal macrophages by conduritol-B epoxide: an in vitro model of the Gaucher cell. AB - Murine peritoneal macrophages were cultured in the presence of conduritol-B epoxide, a specific covalent inhibitor of beta-glucosidase. The inhibition was found to be dose and time dependent. Upon removal of the inhibitor from the culture medium, beta-glucosidase activity recovered to half maximum by 2.2 days. Treatment of macrophages with this inhibitor for 15 days did not affect cell viability, lysosomal enzyme release to the medium, or levels of intracellular lysosomal enzymes, other than beta-glucosidase activity. This inhibition results in the accumulation of glucocerebroside. In vitro studies on the pathobiology of such macrophages whose beta-glucosidase activity has been reduced may be useful toward understanding the pathogenesis of Gaucher disease. PMID- 3087426 TI - Effect of exogenous histone H5 on integration of histone H1 in rat liver chromatin. Correlations with aberrant epsilon-N-methylation of histone H1. AB - Binding modes of histones H1 and H5, and their competition for chromatin-binding sites in rat liver nuclei, were correlated with aberrant N-methylation of H1 histone lysine residues, induced by chicken erythrocyte histone H5, in order to gain more insight into the integration of lysine-rich histones in chromatin. Addition of approx. 2.5 molecules of histone H5 per nucleosome to rat liver nuclei increases the ratio of total basic residues in histones to DNA nucleotides (BR/NT) in the nuclear chromatin from 1.0 to 1.5. At this concentration, approx. 0.7 molecule of histone H5 is bound per nucleosome, and there is no displacement of histone H1 from the nuclear chromatin. If S-adenosyl[Me-3H]methionine is present in the incubation mixture, the aberrant incorporation of labeled methyl groups into histone H1 reaches a maximum at this concentration of histone H5. The radioactivity present in histone H1 from nuclei incubated with labeled AdoMet at a total BR/NT ratio of 1.5: resides mainly in a histone H1 subfraction tentatively identified by Bio-Rex 70 chromatography and acrylamide gel electrophoresis as histone H1c; presents as a single spot upon peptide mapping of tryptic hydrolysates by means of two-dimensional thin-layer chromatography; and elutes in the position of mono-N-methyllysine upon ion-exchange chromatography of histone H1 hydrolysates. Upon further increase of the BR/NT ratio, the following changes are produced: a gradual decrease in radioactive methyl uptake into histone H1; a gradual displacement of histone H1 from the chromatin; increased binding of histone H5 in chromatin, up to a maximum of 3.4 residues per nucleosome; and a slowly increasing uptake of label into histone H5. The combined data from histone H1/H5 binding and histone H1 methylation studies suggest that upon addition of exogenous histone H5 to rat liver nuclei the binding of two lysine-rich histones per nucleosome plays a significant role in the induction of specific changes in chromatin structure, which in vivo may have important functional implications in terms of chromatin condensation and suppression of transcription. PMID- 3087428 TI - Regional distribution of prostaglandin endoperoxide synthase studied by enzyme linked immunoassay using monoclonal antibodies. AB - Prostaglandin endoperoxide synthase transforms arachidonic acid to prostaglandin H2 via prostaglandin G2. The enzyme purified from bovine vesicular gland was given to mice as antigen, and monoclonal antibodies were raised by the hybridoma technique. Two species of the monoclonal antibody recognizing different sites of the enzyme were utilized to establish a peroxidase-linked immunoassay of prostaglandin endoperoxide synthase. Fab' fragment of one of the antibodies was prepared and conjugated to horseradish peroxidase. The conjugate was then bound to prostaglandin endoperoxide synthase, and the labeled enzyme was precipitated by the addition of the other antibody. The peroxidase activity of the immunoprecipitate correlated linearly with the amount of prostaglandin endoperoxide synthase. This sensitive and convenient method to determine the enzyme amount rather than the enzyme activity was utilized to extensively screen the amount of prostaglandin endoperoxide synthase in various bovine tissues. In addition to vesicular gland, platelets and kidney medulla previously known as rich enzyme sources, the immunoenzymometric assay demonstrated a high content of the enzyme in various parts of alimentary tract and a low but significant amount of enzyme in some parts of brain. PMID- 3087429 TI - Composition and incorporation of [3H]arachidonic acid into molecular species of phospholipid classes by cultured human endothelial cells. AB - Based on quantitative high-performance liquid chromatographic analyses of molecular species in selected phospholipid subclasses from culture human umbilical vein endothelial cells, the relative degree of unsaturation was ethanolamine plasmalogens greater than phosphatidylethanolamine greater than phosphatidylcholine. A total of 36 different molecular species were identified in the phosphatidylcholine fraction. Interestingly, the phosphatidylcholine contained a significant amount (11.7%) of the dipalmitoyl species, a lipid normally associated with lung surfactant. The arachidonoyl-containing molecular species of phosphatidylserine/inositol were labeled to the highest extent and the ethanolamine plasmalogens contained the lowest specific radioactivity after incubating [3H]arachidonic acid with human endothelial cells for 4 h. Within each phospholipid subclass the arachidonoyl species where both acyl groups of the phospholipid are unsaturated (20:4-20:4, 18:2-20:4 + 16:1-20:4, and 18:1-20:4) had higher specific radioactivities, after labeling with [3H]arachidonic acid, than those that contained saturated aliphatic chains (16:0-20:4 and 18:0-20:4). This indicates that the unsaturated species have higher turnover rates. PMID- 3087430 TI - Characterization of prostaglandin endoperoxide synthase from a human cell line. AB - Prostaglandin endoperoxide synthase has been purified from the recently established human lung tumor cell line, Lu-65. By gel filtration, the purified enzyme migrated with a relative molecular weight of 115,000, unlike the ovine enzyme, which migrated at 155,000. Two protein bands of 45,000 and 68,000 were seen when the purified Lu-65 enzyme was fractionated under reducing conditions by SDS-polyacrylamide gel electrophoresis; in contrast, purified ovine prostaglandin endoperoxide synthase showed the Mr 68,000 band under the same conditions. The purified Lu-65 enzyme showed both cyclooxygenase and hydroperoxidase activities, and metabolized [3H]arachidonic acid to 3H-labeled products that, when separated by reverse-phase HPLC, co-eluted with authentic prostaglandin D2 and prostaglandin E2. An apparent Km for arachidonic acid of 3 mM was measured for the purified enzyme, and the crude membrane-bound enzyme showed an apparent Km of 1.6 mM. Under the same conditions, an apparent Km of 17 microM was measured for the purified ovine enzyme. PMID- 3087431 TI - Distinct effect of forskolin and interferon-gamma on cell proliferation and regulation of histocompatibility antigen expression in hematopoietic cells. AB - The adenylate cyclase activator, forskolin, was found to induce expression of class I and class II major histocompatibility complex antigens in a B precursor cell line, Reh, as well as in a B lymphoid cell line, Raji. No such effect was, however, observed when the promyelocytic cells line HL-60 was treated with either forskolin or the cAMP analogue 8-bromoadenosine cyclic monophosphate. As expected, all three cell lines showed reduced proliferation upon forskolin treatment. Forskolin induced expression of class I and class II major histocompatibility complex antigens in cell lines not affected by interferon gamma and vice versa, indicating that cAMP is not involved in the regulation of histocompatibility antigens by interferon-gamma. We also compared the effect of interferon-gamma and 12-O-tetradecanoylphorbol 13-acetate on major histocompatibility complex class I and class II expression, and despite differences in the response on the tested cell lines, we can not at this point exclude the possibility that protein kinase C is involved in the action of interferon-gamma. PMID- 3087432 TI - Dexamethasone-induced stimulation of arachidonic acid release by U937 cells grown in defined medium. AB - Since the presence of serum in culture media has been shown to alter prostaglandin production, as well as to interfere with the action of anti inflammatory drugs, we have studied the effect of dexamethasone, a potent steroidal anti-inflammatory drug, on the metabolism of arachidonic acid by human monocyte-like cells (U937) grown in a fully defined medium. Under these culture conditions, dexamethasone (10(-6) M, 24 h) induced a marked stimulation of the release of unmetabolized arachidonic acid into the culture medium. The steroid also induced an inhibition of cell proliferation which became significant only after 48 h of treatment. The accumulation of arachidonic acid in the medium after steroid treatment was associated with a significant inhibition of cell acyltransferase activity, suggesting that steroids may also act upon arachidonic acid metabolism at sites other than those of phospholipase activity. PMID- 3087433 TI - [Effect of arachidonic acid on the physical properties of bilayer and annular lipids of synaptic membranes]. AB - It has been found by fluorescence analysis of pyrene excimerization that arachidonic acid while decreasing microviscosity of lipid bilayer increases it in the annular lipid zone. After incorporation of fatty acid into the membrane the annular lipid acquires the properties of a cooperative system manifested in the appearance of thermal transition near 25 degrees C. PMID- 3087434 TI - Neuroleptic drug-induced alterations on neonatal growth and development. I. Prenatal exposure influences birth size, mortality rate, and the neuroendocrine system. AB - Subcutaneous injection of codeine or phenobarbital, and feeding amphetamine to rats during gestation and lactation caused irregularities in mortality rates, growth, development, and associated neuroendocrine events within the newborns. Most striking was the subnormal birth size, increased mortality rate, and decreased hypothalamic growth hormone-releasing activity of neonates of mothers fed the highest dose of amphetamine. PMID- 3087435 TI - Quasi-elastic light scattering from migrating chemotactic bands of Escherichia coli. III. Studies of band formation propagation and motility in oxygen and serine substrates. AB - A series of light scattering experiments have been performed to study both macroscopic aspects of band formation and propagation and microscopic motility parameters of Escherichia coli in the combined substrate gradients of oxygen and serine. From the band formation experiment the conclusion is drawn that a minimum threshold gradient of the substrate is required for bacteria to form a band. From the band propagation experiment in the serine substrate the motility coefficient mu and chemotactic coefficient delta are determined. A separate quasi-elastic scattering experiment has been made with a propagating band to obtain three microscopic motility parameters: mean twiddle time tau 1, mean run time tau 2, and mean run speed V2. Finally, a scaling argument is made to connect the macroscopic parameters mu and delta with the microscopic parameters tau 1, tau 2, and V2, thus achieving a unified understanding of macroscopic and microscopic aspect of chemotaxis. PMID- 3087436 TI - Galactosyltransferase activity is not localized to the brush border membrane of human small intestine. AB - A recent report [Roth et al. (1985) J. Cell Biol. 100: 118-125], using immunocytochemical techniques, claimed that human duodenal galactosyltransferase is located predominantly on the external aspect of enterocyte brush border membranes. Analytical subcellular fractionation by sucrose density gradient centrifugation of human jejunum biopsy homogenates demonstrated that galactosyltransferase activity is localized to the Golgi fraction (equilibrium density of 1.14 g cm-3) and is not found in significant amounts in the brush border membrane (equilibrium density of 1.22 g cm-3). PMID- 3087437 TI - Release of galactosyltransferase from human platelets and a subset of monocytes in culture. AB - We show that human monocytes and platelets release considerable amounts of galactosyltransferase (GT) in serum-free culture as measured by the amount of incorporation of 3H-galactose into ovalbumin. Enzyme production was the greatest among medium-sized mononuclear cells separated by counter-current elutriation. The cells were adherent and positive for the monocyte-specific monoclonal antibody FMC-32. The activity in the monocyte fractions was not due to platelet contamination as shown from experiments in which platelets or platelet antigens were eliminated. Cell viability decreased by less than 3% during the overnight culture, and results from cell disruption experiments showed that the enzyme was not released from dead or dying cells. Cycloheximide inhibited release during 20 hours culture. Approximately 50% of the enzyme in the cell culture supernatant was pelletable at 105,000 g. Platelets released the enzyme more rapidly than did monocytes and were readily stimulated by thrombin to release more GT. Thrombin also increased monocyte GT activity after overnight incubation, but other stimulants, zymosan and lipopolysaccharide (LPS), decreased release. We conclude that GT is released into culture supernatants by platelets and by a subset of peripheral blood monocytes. These sources may account for a significant proportion of the serum enzyme and may be important in modification of extracellular carbohydrates during inflammation and coagulation. PMID- 3087438 TI - DDAVP infusion in five patients with type Ia glycogen storage disease and associated correction of prolonged bleeding times. AB - Five patients with glycogen storage disease type I (GSD-I) were evaluated for a bleeding diathesis and subsequently were given an infusion of 1-deamino-8-D arginine vasopressin (DDAVP). Although platelet counts were normal or slightly elevated, the baseline template bleeding times were prolonged in four of the patients. Prothrombin times and activated partial thromboplastin times were normal, while ADP- and epinephrine-induced platelet aggregations were absent in the three patients tested. Ristocetin- and collagen-induced platelet aggregations were abnormal. Laurell and immunoradiometric determinations of the factor VIII related antigen (vWf antigen) were decreased. Glyoxyl agarose gel electrophoresis of the patients' plasma revealed abnormal multimer patterns in four of the five patients. After the DDAVP infusion the platelet aggregation abnormalities persisted; however, the bleeding time and the von Willebrand antigen and activity corrected. We conclude that GSD-Ia patients may have a metabolically acquired form of von Willebrand's syndrome as well as an acquired intrinsic platelet defect, and that DDAVP may be useful in the management of bleeding in these patients. PMID- 3087439 TI - Carbonic anhydrase: a marker for the erythroid phenotype in acute nonlymphocytic leukemia. AB - Protein markers are often used to corroborate the morphological subtyping of hematopoietic malignancy. Most commonly, surface markers are used for the phenotyping of hematopoietic cells; however, internal proteins have also been used as markers. Glycophorin, hemoglobin A, hemoglobin F, and transferrin have all been used as markers for the erythroid phenotype. We have recently shown that carbonic anhydrase is constitutively and aberrantly expressed in two erythroleukemic cell lines. We here show that it is also present in high levels in primary erythroleukemic blasts and that it is a useful marker for the M6 phenotype when classifying acute nonlymphocytic leukemia. PMID- 3087440 TI - Platelet membrane microparticles in blood bank fresh frozen plasma and cryoprecipitate. AB - Cryoprecipitate has been demonstrated to correct the bleeding abnormality of patients with some congenital (storage pool disease) and acquired (uremia) platelet abnormalities, but the reason for this effect is unknown. We found significant platelet contamination in plasma harvested to prepare fresh frozen plasma and cryoprecipitate. The platelet membrane microparticles produced by freezing and thawing of the plasma were highly concentrated in cryoprecipitate and may contribute to its therapeutic effect. PMID- 3087442 TI - Accelerated degradation of carbaryl and carbofuran in a flooded soil pretreated with hydrolysis products, 1-naphthol and carbofuran phenol. PMID- 3087441 TI - Effects of purified bacterially synthesized murine multi-CSF (IL-3) on hematopoiesis in normal adult mice. AB - Normal adult C57BL, BALB/c, and C3H/HeJ mice were injected intraperitoneally three times daily for up to 6 days with 102,000 U (200 ng) per injection of purified, bacterially synthesized, Multipotential colony-stimulating factor (CSF) (Interleukin-3) (rMulti-CSF) and compared with control mice injected with serum/saline with or without added endotoxin (1 ng/mL). Mice injected with rMulti CSF exhibited tenfold rises in blood eosinophil and twofold to threefold rises in neutrophil and monocyte levels. The spleens from mice injected with rMulti-CSF showed a 50% increase in weight, elevated levels of maturing granulocytes, eosinophils, nucleated erythroid cells and megakaryocytes, and up to 100-fold rises in mast cells. Progenitor cell frequencies in the spleen were elevated sixfold to 18-fold. No significant changes were observed in the marrow. Sixfold to 15-fold rises were observed in peritoneal cell populations of mice injected with rMulti-CSF with evidence of increased peritoneal macrophage phagocytic activity. Livers of C57BL mice, but not of the other strains, exhibited increased numbers of infiltrating hematopoietic cells whereas rises in mast cell numbers were observed in the mesenteric lymph node, skin, and gut in BALB/c and C3H/HeJ mice. Endotoxin was excluded as being responsible for the observed changes except possibly those involving peritoneal macrophage phagocytic activity. The results indicate that the injection of normal mice with rMulti-CSF significantly stimulates the same types of hematopoietic populations as are stimulated in vitro by Multi-CSF and indicate that this and other CSFs should be useful in stimulating hematopoietic repopulation and functional activity in vivo. PMID- 3087443 TI - Diflubenzuron surface residues in Florida citrus. PMID- 3087444 TI - Microsomal detoxication enzyme responses of the marine snail, Thais haemastoma, to laboratory oil exposure. PMID- 3087445 TI - Comparative toxicity of two Dimilin formulations to the grass shrimp, Palaemonetes pugio. PMID- 3087446 TI - PCB removal by conventional water treatment: effect of chemical coagulation and chlorination. PMID- 3087447 TI - Modified multiresidue method for chlordane, toxaphene, and polychlorinated biphenyls in fish. PMID- 3087448 TI - Effect of oil matrix on PCB quantification. PMID- 3087449 TI - Nutritional support in growth-retarded Crohn's patients. PMID- 3087450 TI - The influence of seizure type and medication on psychiatric symptoms in epileptic patients. AB - The influence of type of seizure and medication on psychological disability was assessed using the Standard Psychiatric Interview in matched epileptic patients. In comparison to patients with idiopathic tonic-clonic seizures, those with temporal lobe epilepsy complained of more irritability and impaired concentration, and were rated as more depressed and slowed up. Compared to patients on phenytoin, those on carbamazepine complained of more sleep disturbance and were more likely to be taking an hypnotic. PMID- 3087451 TI - Post-treatment fertility in patients with testicular cancer. III. Influence of radiotherapy in seminoma patients. AB - Sperm analysis and serum hormone measurements (LH, FSH, testosterone) were performed in 29 patients after orchiectomy for seminoma before and after irradiation. Before radiotherapy 14 of 20 orchiectomized patients were azoospermic or had impaired spermatogenesis. A minimum sperm count was found 1 year after radiotherapy with gradual improvement up to 2 years. The recovery of sperm cell production was impaired most in patients with pre-treatment sperm counts less than 3 million/ml. Serum testosterone remained at low normal levels throughout the observation period. The mean serum FSH was increased 1 year after radiotherapy but returned to normal in 50% of patients within 3 years after treatment. This post-treatment increase in FSH was significantly correlated with increased pre-treatment FSH but not with the gonadal dose, which was 1 to 3% of the target dose. Severe disturbances in spermatogenesis, observed 2 to 3 years after radiotherapy for early seminoma, are likely to be the expression of a highly impaired pre-treatment sperm cell production and only to a lesser degree dependent on the irradiation of the remaining testicle. PMID- 3087452 TI - Steroids, the eye, and general practitioners. PMID- 3087453 TI - Differential diagnosis of dementia. PMID- 3087454 TI - Height at diagnosis of insulin dependent diabetes in patients and their non diabetic family members. AB - Height at the onset of insulin dependent diabetes mellitus was evaluated in 200 newly diagnosed children, 187 non-diabetic siblings, and 169 parents. Diabetic children 5-9 years of age at diagnosis were consistently taller than the national average. Non-diabetic siblings of the same age were also tall. Diabetic children aged 14 or over at diagnosis were short, while their siblings and parents were of normal height. Diabetic children positive for islet cell antibodies were taller than those without islet cell antibodies. No association between height and HLA antigens was found. Non-diabetic siblings at high risk for the disease were closer in height to the diabetic children than were the lower risk, non-diabetic siblings. Siblings, particularly those under 10, were also significantly more obese than the general population. Deviations in growth in patients with insulin dependent diabetes mellitus appear to be related to age at diagnosis and a factor(s) not related to parental height. PMID- 3087455 TI - Linoleic acid content in adipose tissue and coronary heart disease. AB - The possibility of an inverse relation between essential fatty acids in adipose tissue, in particular linoleic acid, and mortality from coronary heart disease was studied by a cross sectional survey of random population samples of apparently healthy men aged 40-49 from four European regions with differing mortality from coronary heart disease. The proportion of linoleic acid in adipose tissue was lowest in men from north Karelia, Finland, where mortality from coronary heart disease is highest, and highest in men from Italy, where mortality is lowest, with intermediate proportions in men from Scotland and south west Finland. Similar gradients were observed for the desaturation and elongation products dihomo-gamma-linolenic and arachidonic acid. The proportion of saturated fatty acids in adipose tissue was highest in Finland, intermediate in Scotland, and lowest in Italy. Italian men also had the highest proportion of oleate in their adipose tissue and the lowest proportion of myristoleate and palmitoleate. Finnish men were more obese and had a higher blood pressure. Serum cholesterol concentration was higher in north Karelia and south west Finland than in Scotland or Italy. High density lipoprotein (HDL) cholesterol concentrations reflected the regional differences in serum cholesterol, being higher in Finland and lower in Italy. The ratios of HDL cholesterol to total cholesterol, however, did not differ. The regional differences in linoleic acid in adipose tissue remained highly significant when the observed differences in other known risk factors for coronary heart disease among the four areas were taken into account by multivariate analysis. The gradients in proportions of polyunsaturated fatty acids probably reflect differences in dietary intake of linoleic acid. PMID- 3087456 TI - Relief of acute pain in herpes zoster ophthalmicus by stellate ganglion block. PMID- 3087457 TI - Urinary sodium excretion in 4-6 year old children: a cause for concern? PMID- 3087458 TI - Acute non-A non-B hepatitis after typhoid fever. PMID- 3087459 TI - Preventing psychological problems in children of divorce: general practitioner's role. PMID- 3087460 TI - Effects of strong government measures against tobacco in Hong Kong. AB - The government of Hong Kong grasped the political nettle of control of tobacco in the early 1980s, since when a comprehensive policy of legislation, education, and publicity, together with large increases in taxation on tobacco products, has been introduced. This has led to almost all of the population of Hong Kong having knowledge of the harmful effects of tobacco and of antismoking measures taken by the government. From 1982 to 1984 the number of people who smoked daily fell appreciably from 888 300 to 744 500, a reduction of 16%, while the number of teenage smokers was halved (from 22 600 to 11 200). Government commitment is crucial in programmes against tobacco in developing countries; without it antismoking efforts are unlikely to be successful. PMID- 3087461 TI - The doctor, the patient, and their contract. III. Alternative contracts: are they viable? PMID- 3087462 TI - Prevalence of hepatitis B virus infection among black children in Soweto. AB - Roughly 15% of black children in rural areas of southern Africa are carriers of the hepatitis B virus. The purpose of the present study was to determine the prevalence of chronic hepatitis B virus infection among urban black children born and growing up in Soweto. A total of 2364 children were studied, ranging in age from 3 to 19 years, and of these, 1319 (56%) were girls. The children were drawn from the highest and the lowest socioeconomic classes. Serum samples were tested for all hepatitis B virus markers as well as IgG antibody against hepatitis A virus. HBsAg was detected in 23 (0.97%) of the children, anti-HBc and anti-HBs together in 155 (6.6%), anti-HBc alone in 17 (0.7%), and anti-HBs alone in 72 (3%). Of the 2364 children, 2097 (88.5%) were negative for all hepatitis B virus markers. IgG antibody to hepatitis A virus was present in 175 (97%) of a sample of 179 children. There was no difference in prevalence of hepatitis B virus markers between children from the upper and lower socioeconomic classes. HBsAg was more common in boys (16 out of 1043 (1.5%) than girls (seven out of 1321 (0.57%), and the prevalence of all hepatitis B virus markers increased with age. The youngest carrier of hepatitis B virus was 7 years old. The remarkable difference in the hepatitis B virus carrier rate between urban and rural black children offers a unique opportunity to investigate the favourable influences operating in an urban environment to limit the prevalence of hepatitis B virus infection. PMID- 3087463 TI - On being a masseuse in Thailand. PMID- 3087464 TI - ABC of resuscitation. Post resuscitation care. PMID- 3087465 TI - Report from the PHLS Communicable Disease Surveillance Centre. PMID- 3087466 TI - Use of steroid eye drops in general practice. PMID- 3087467 TI - Incidence of inappropriate treatment of herpes simplex keratitis with topical steroids. PMID- 3087468 TI - Morale among Soviet doctors. PMID- 3087469 TI - Court of Appeal rules that GMC charges against Gee are acceptable. PMID- 3087470 TI - Haemoglobin concentration and linear cardiac output, peripheral resistance and oxygen transport. PMID- 3087472 TI - Role of an immunization advisory service. PMID- 3087471 TI - Orthopaedic scooter. PMID- 3087473 TI - Biosynthesis of thromboxane in patients with systemic sclerosis and Raynaud's phenomenon. PMID- 3087474 TI - Increase in bronchopulmonary infection due to Branhamella catarrhalis. PMID- 3087475 TI - Bleeding from peptic ulcers and use of non-steroidal anti-inflammatory drugs. PMID- 3087476 TI - IVF update. PMID- 3087477 TI - Reducing the use of laboratory tests. PMID- 3087478 TI - Reaction to food additives. PMID- 3087479 TI - Pseudo-obstruction. PMID- 3087480 TI - Recognising cardiac arrest and providing basic life support. PMID- 3087481 TI - Chronic inflammatory bowel disease, cigarette smoking and use of oral contraceptives. PMID- 3087482 TI - Bleeding oesophageal varices. PMID- 3087483 TI - Staying cool with a hot test: gastroenterologists and 75SeHCAT. PMID- 3087484 TI - Clinical competence and curiosity. PMID- 3087485 TI - Bereaved children. PMID- 3087486 TI - Response to inhaled histamine and 24 hour sodium excretion. AB - A relation between the prevalence of asthma and economic development has been suggested by studies in migrants and other surveys in developing countries. That this correlation might be partially explained by an increased intake of salt in the diet is supported by the observation that sales of table salt in the different regions of England and Wales are independently correlated with mortality from asthma for men and for children. As part of a wider survey of asthma 138 men living in two Hampshire villages and aged 18-64 were given a bronchial histamine challenge test and had their 24 hour urinary excretion of sodium measured. Bronchial reactivity was strongly related to 24 hour excretion of sodium after allowing for the effects of age, atopy, and cigarette smoking, there being on average a 10-fold difference in reactivity over the 95% range of sodium excretion recorded in the study. The data suggest that a high sodium diet may potentiate bronchial reactivity. PMID- 3087487 TI - Recent trends in breast surgery in the United States and United Kingdom. AB - Data on breast surgery from national samples of patients discharged from hospital in the United States and in England and Wales were reviewed for the years 1970 80. In the United States the rate of breast surgery increased dramatically in 1974 and 1975, but in Britain it remained constant and well below the level in the United States. In both countries the proportion of radical mastectomies declined and the proportion of less extensive procedures rose. The increase in mastectomy rates in the United States probably resulted from increased public concern about breast cancer and from the promotion of breast screening in the mid 1970s. The costs, morbidity, and early mortality associated with a higher rate of mastectomy are substantial and the advantages unclear. PMID- 3087488 TI - Quality of life after myocardial infarction: effect of long term metoprolol on mortality and morbidity. AB - A double blind randomised study of 154 patients with myocardial infarction assigned to metoprolol (100 mg twice daily) and 147 assigned to placebo compared the effects of treatment in relation to health state over three years. Health state was evaluated by a new method based on the average number of days spent in each of seven mutually exclusive categories of health. The scale took into account death, history of serious complications, functional state, and side effects of treatment. Of the maximum attainable 1095 days alive during the three years patients given metoprolol attained 992 days and those given placebo 964 days. During the period alive the metoprolol treated group spent an average of 278 days in an optimal functional state as compared with 176 days for the placebo treated group. This included 221 and 156 days respectively in a completely asymptomatic state (that is, without either cardiac symptoms or side effects of treatment). The time spent with a serious non-fatal complication was shortened by 56 days in the metoprolol group. The overall differences between the groups were statistically significant (p = 0.03). Aside from bringing an improved quality of life after myocardial infarction, metoprolol may add up to one month to life expectancy for three years of treatment. PMID- 3087489 TI - Limited joint mobility and Dupuytren's contracture in diabetic, hypertensive, and normal populations. PMID- 3087490 TI - Legionnaires' disease cluster and reduction in hospital hot water temperatures. PMID- 3087491 TI - Out of depth, out of breath. PMID- 3087492 TI - New portable infusion pump for prolonged subcutaneous administration of opioid analgesics in patients with advanced cancer. PMID- 3087493 TI - A depressing pursuit of quality. PMID- 3087494 TI - Complementary medicine and the general practitioner. AB - The attitudes to complementary medicine of a random sample of general practitioners in Avon were assessed. A questionnaire was sent to 200 general practitioners, of whom 145 responded. The treatments studied were acupuncture, homoeopathy, herbal medicine, spinal manipulation, faith healing, and hypnosis. Of the 145 general practitioners, 55 (38%) had received some training in complementary medicine and 22 (15%) wished to arrange training. Overall, general practitioners knew little about the techniques of complementary medicine. Despite this 86 doctors (59%) thought that the complementary techniques being assessed were useful to their patients: 110 (76%) had referred patients for this type of treatment over the past year to medically qualified colleagues and 104 (72%) had referred patients to non-medically qualified practitioners. Most (93%) of those who responded believed that complementary practitioners needed statutory regulation; only 3% thought that they should be banned. The method of regulation most favoured was through a central and independent national body. General practitioners' views about complementary techniques were most influenced (in a positive manner) by observed benefits to their patients (41%) and personal or family experience of benefit (38%). The results of the study show a surprisingly high interest in complementary medicine among general practitioners in the Avon area. PMID- 3087495 TI - Measles, mumps, and rubella: the need for a change in immunisation policy. AB - There is growing evidence that the present policy of childhood immunisation in the United Kingdom is inadequate. It is unlikely ever to achieve complete eradication of the congenital rubella syndrome and measles, and the problem of mumps has not even begun to be addressed. After a coordinated campaign to increase uptake of immunisation in Fife the uptake of rubella immunisation in teenage girls increased from 75% in 1981 to 94% in 1985 and the uptake of measles vaccination in preschool children from 55% in 1981 to 81% in 1985. There are a few girls each year who do not accept rubella immunisation, whose immune state is unknown, and who are consequently at risk of rubella during future pregnancies. Despite the increased uptake of measles vaccine over the past four years there is currently an epidemic of measles in Fife, with 544 notified cases in the first quarter of 1986. In 1984, 19 Fife residents were admitted to hospital because of complications of mumps. The time is ripe for a complete reassessment of the national immunisation policy. PMID- 3087496 TI - Cancer self help groups: an inside view. PMID- 3087497 TI - Molecular biology at the bedside. PMID- 3087498 TI - ABC of resuscitation. Training manikins. PMID- 3087500 TI - Maternal mortality and the postpartum interval. PMID- 3087499 TI - Haemolytic-uraemic syndrome: clinical experience of an outbreak in the West Midlands. AB - In 1982-3, 35 children from the West Midlands developed the haemolytic-uraemic syndrome. This was a higher incidence than expected and included an epidemic localised to the Wolverhampton area in July 1983 which comprised 11 cases in two weeks. Twenty three children were treated with dialysis, of whom three died. Six patients developed chronic renal failure, four of them from Wolverhampton. Extrarenal manifestations included neurological sequelae in four, two of whom also developed insulin dependent diabetes mellitus and chronic renal failure. Cardiomyopathy occurred in one child, who also had chronic renal failure. The outcome of these 35 patients was not predictable from prognostic criteria derived from previous experience in Britain. This, together with the high prevalence of extrarenal disease and the geographical localisation of the 1983 outbreak, suggested an aetiological agent new to the region. Faeces from 10 patients were examined for verotoxin producing Escherichia coli, and positive strains of serotype O157.H7 were found in three patients during the Wolverhampton outbreak. PMID- 3087501 TI - Missed malignant melanomas. PMID- 3087502 TI - Screening for intrauterine growth retardation using ratio of mid-arm circumference to occipitofrontal circumference. PMID- 3087503 TI - Sensitivity of neonates to tuberculin after BCG vaccination. PMID- 3087504 TI - Sexual abuse of children in Leeds. PMID- 3087505 TI - Enprostil and ranitidine in duodenal ulcer healing. PMID- 3087506 TI - General practitioners' practice expenses. PMID- 3087507 TI - Reye's syndrome and aspirin. PMID- 3087509 TI - What price academic general practice? PMID- 3087508 TI - Airing operating theatres. PMID- 3087510 TI - Severity scoring in intensive care. PMID- 3087511 TI - Bone mineral content in Polynesian and white New Zealand women. AB - The forearm bone mineral content of Polynesian and European women in New Zealand was measured to assess whether the inter-racial differences found in other populations also occurred in these two groups. The bone mineral content of the nondominant distal radius and ulna was measured by single photon absorptiometry in 123 European and 80 Polynesian women. The mean values were about 20% higher in Polynesians than in Europeans. The reason for this difference in bone mineral content is unknown but the findings do show that high bone density is not confined to African races and that inter-racial differences in bone mineral content may be more common than has been thought hitherto. PMID- 3087512 TI - Morphine intoxication in renal failure: the role of morphine-6-glucuronide. AB - Patients with impaired renal function may experience severe and prolonged respiratory depression when treated with morphine. This has been attributed to accumulation of the drug during renal failure. Three patients are described who had classical signs of intoxication with morphine in the absence of measurable quantities of morphine in the plasma. The observed clinical effect is attributed to accumulation of the pharmacologically active metabolite morphine-6 glucuronide, which is usually renally excreted. It is concluded that morphine does not accumulate in patients with renal failure but that accumulation of metabolites does occur. The previously reported observations of morphine accumulation during renal failure probably result from the use of radioimmunoassays that cannot distinguish between morphine and morphine-6 glucuronide. Thus the apparent morphine concentration measured with these assays in fact reflects the total quantity of morphine and morphine-6-glucuronide present. PMID- 3087513 TI - Treatment of cancer associated hypercalcaemia with combined aminohydroxypropylidene diphosphonate and calcitonin. AB - Eight patients with cancer associated hypercalcaemia were treated with the combination of aminohydroxypropylidene diphosphonate and salmon calcitonin for six days. Serum calcium concentration fell significantly within 24 hours of starting treatment due to a reduction in bone resorption and renal tubular calcium reabsorption. In the longer term hypercalcaemia was controlled by a further progressive reduction in bone resorption, which persisted for six days after treatment was stopped. Renal tubular calcium reabsorption, however, remained suppressed only during drug treatment. The rapid fall in serum calcium was attributable to the acute renal and skeletal effects of calcitonin, whereas in the longer term control of hypercalcaemia was due to diphosphonate mediated suppression of bone resorption. In view of the rapid effect and lack of toxicity, combined treatment with aminohydroxypropylidene diphosphonate and calcitonin would be of particular value in patients with severe hypercalcaemia in whom a quick but sustained reduction in the serum calcium concentration is desired. PMID- 3087515 TI - Self poisoning with oral cadmium chloride. PMID- 3087514 TI - Benign melanocytic naevi as a risk factor for malignant melanoma. AB - Examination of 180 patients with cutaneous malignant melanoma and 197 control patients in a case-control study showed that the risk of melanoma is strongly related to numbers of benign melanocytic naevi (moles). Some unusual features of naevi--a diameter exceeding 7 mm, colour variation, and irregular lateral outline -also showed a strong association with the risk of melanoma, but the relation of numbers of naevi to risk was present even in the group of patients whose naevi had none of these unusual features. Biopsy of clinically atypical naevi from several of the patients at highest risk generally did not show dysplastic histology. Thus a group of people at high risk of melanoma may be identified by using simple clinical assessment of naevi. PMID- 3087516 TI - Assessment of thyroid function: complications after treatment with fenoprofen. PMID- 3087517 TI - Lyme disease in a Hampshire child--medical curiosity or beginning of an epidemic? PMID- 3087518 TI - Asthma caused by pulverised fuel ash. PMID- 3087519 TI - Ovarian ultrasonography highlights precision of symptoms of ovulation as markers of ovulation. PMID- 3087520 TI - Preventing psychological disorders in children of divorce: guidelines for the general practitioner. PMID- 3087521 TI - The Mackenzie report: general practice in the medical schools of the United Kingdom--1986. PMID- 3087522 TI - Os subtibiale mistaken for a recent fracture. PMID- 3087523 TI - Consultation skills of young doctors: II--Most young doctors are bad at giving information. AB - Forty young doctors, half of whom had had feedback training in interviewing as students, were assessed five years later. Each interviewed three patients and after being given results of examination, investigations, and diagnosis and prognosis returned to discuss them with each patient for 10 minutes. These discussions were filmed on videotape and evaluated. There was no difference between the scores of interview trained and control doctors. Though most gave simple information on diagnosis and treatment, few mentioned investigations, aetiology, or prognosis. Very few obtained and took any account of patients' views or expectations of these matters. Some young doctors do discover for themselves how best to give patients information and advice, but most remain extremely incompetent. This is presumably because they get no training as students in this important aspect of clinical practice. This deficiency should be corrected, and competence tested before qualification to practise. PMID- 3087524 TI - Should general practitioners be informed of patients' convictions for drug offences? PMID- 3087525 TI - ABC of resuscitation. Resuscitation of infants and children. PMID- 3087527 TI - Acute adrenal crisis precipitated by thyroxine. PMID- 3087528 TI - Bed blocking in Bromley and Belfast. PMID- 3087526 TI - Pseudo-obstruction. PMID- 3087529 TI - Bed numbers and good medical education. PMID- 3087530 TI - Occupational asthma due to methyl methacrylate bone cement. PMID- 3087531 TI - Ophthalmopathic immunoglobulin not detected in patients with Graves' ophthalmopathy. PMID- 3087532 TI - Antibody response and clinical reactions in children given measles vaccine with immunoglobulin. PMID- 3087533 TI - Systemic candidiasis in heroin addicts. PMID- 3087534 TI - Asymptomatic microscopical haematuria. PMID- 3087535 TI - Cytology brush entrapment: a hazard in the stomach postoperatively. PMID- 3087536 TI - Orthopaedic scooter. PMID- 3087538 TI - Acute epiglottitis. PMID- 3087537 TI - Happiness is: iron. PMID- 3087539 TI - Foot surgery by chiropodists criticised. PMID- 3087540 TI - Incompetence in medical practice. PMID- 3087541 TI - Smoking, drinking, and polycythaemia. PMID- 3087542 TI - Faecal incontinence is not inevitable. PMID- 3087543 TI - Spoiled soft contact lenses. PMID- 3087544 TI - A senseless sacrifice: the fate of intercalated degrees. PMID- 3087545 TI - Adolescent suicide: preventive considerations. PMID- 3087547 TI - Confidential inquiry into perioperative deaths. PMID- 3087546 TI - Non-steroidal anti-inflammatory drugs and the kidney. PMID- 3087548 TI - The truth about the NHS? PMID- 3087549 TI - Transcutaneous oxygen tension during exercise in patients with claudication. AB - Transcutaneous oxygen tension (TcPO2) was monitored during maximal exercise in 10 patients with stable moderate to severe claudication. The TcPO2 fell by 16% at the onset of claudication and 32% at the maximum walking distance. On resting this decrease reached a maximum of 66% roughly four minutes after exercise. This was followed by a steady recovery. The percentage changes were reproducible in each patient and were appreciably different from the TcPO2 exercise profiles of normal healthy volunteers. TcPO2 monitoring during exercise is a simple, reproducible, cheap, and useful technique for assessing claudication and compares favourably with other techniques used to quantify this condition. PMID- 3087550 TI - Treatment of the premenstrual syndrome by subcutaneous estradiol implants and cyclical oral norethisterone: placebo controlled study. AB - The hypothesis that the many non-specific changes normally associated with cyclical ovarian activity are the primary aetiological factors in the premenstrual syndrome was tested by suppressing ovulation with subcutaneous oestradiol implants. Sixty eight women with proved premenstrual syndrome were treated under placebo controlled conditions for up to 10 months in a longitudinal study. Active treatment was combined with cyclical oral norethisterone to produce regular withdrawal periods. Symptoms were monitored with daily menstrual distress questionnaires, visual analogue scales, and the 60 item general health questionnaire. Of the 35 women treated with placebo 33 improved, giving an initial placebo response rate of 94%. The placebo effect gradually waned, but the response to the active combination was maintained for the duration of the study. Analysis of the prospective symptom ratings showed a significant superiority of oestradiol implants over placebo after two months for all six symptom clusters in the menstrual distress questionnaire. Changes seen in the retrospective assessments were less significant but the trend was the same. Treatment with oestradiol implants and cyclical progestogen was well tolerated and appears to be both rational and effective for severe cases of the premenstrual syndrome. PMID- 3087551 TI - Associations between symptoms of irritable colon and psychological and social conditions and lifestyle. AB - In a survey of risk factors for coronary heart disease 14 102 middle aged men and women answered a questionnaire on lifestyle, diet, and health, including symptoms of functional abdominal disorders. The overall prevalence of reports of one or both of the abdominal symptoms of "bloating and rumbling" or "cramping abdominal pain" was 28% in men and 35% in women. Only a weak negative association between age and prevalence of reported pain was found in both sexes. Women reported abdominal symptoms, especially cramping abdominal pain, significantly more commonly than men. In a multiple regression analysis abdominal symptoms were much more strongly associated with symptoms of mental stress such as depression, sleeping difficulties, problems of coping, and the use of analgesics than with lifestyle, dietary, and social variables together. The association was stronger in subjects reporting both symptoms. This strong and consistent association between functional abdominal disorders and psychological and social problems suggests that action other than prescribing drugs, diets, or radiography is required. PMID- 3087552 TI - Failure of child safety seat to prevent death. PMID- 3087554 TI - Severe hyperglucagonaemia during treatment with oxymetholone. PMID- 3087553 TI - The real cost of joint replacement. PMID- 3087556 TI - Simple scale for assessing level of dependency of patients in general practice. AB - A rating scale has been designed for assessing the degree of dependency of patients in general practice. An analysis of the elderly and disabled patients in a two doctor practice is given as an example of its use and simplicity. PMID- 3087555 TI - Where do lean diabetics inject their insulin? A study using computed tomography. PMID- 3087557 TI - A comprehensive bibliography database using a microcomputer. AB - A system was implemented using a commercial database management program and a microcomputer for computerising references from journals and other sources. In addition to the citation, the user can enter the address of the institution where the study was carried out, a description of the article and of the work, key words, and an abstract. References are added, edited, searched for, displayed on screen, typed on paper, or sent to a text file, using selection criteria entered by the user. When a search is performed the printout will include the abstract of each paper, similar to that obtained from larger bibliographic services. The computer also writes requests for reprints. This program now holds over 30 000 references and has been in use for over three years. Such a system is beneficial for personal study, for writing books, articles, and theses, and for use by institutions, departments, and small libraries. PMID- 3087558 TI - The Edinburgh intercalated honours BSc in pathology: evaluation of selection methods, undergraduate performance, and postgraduate career. AB - In a study of 60 students who entered the intercalated honours BSc course in pathology at the University of Edinburgh over 10 years the conventional criteria of academic excellence and motivation were shown to be appropriate for the selection of honours students. When compared with classmates who did not take the intercalated year but who had shown similar high academic ability in the preclinical course the students who had taken the honours BSc did better in the remainder of the undergraduate curriculum. Of 42 honours students, 18 (43%) entered academic careers, particularly in pathology and medicine, but there was no observed tendency for students without honours BSc to do so. Although it is impossible to establish a causal relation between taking the honours course and subsequent academic distinction, the results suggest that the intercalated honours BSc in pathology serves a useful function in introducing able students into academic careers. The findings justify the financial support made available to such students during their intercalated year by the Medical Research Council and the Scottish Education Department. PMID- 3087559 TI - Strokes among black people in Harare, Zimbabwe: results of computed tomography and associated risk factors. AB - Computed tomography was performed and risk factors evaluated in 100 consecutive adult patients presenting to the two teaching hospitals in Harare with a clinical diagnosis of stroke. The mean age of the patients was 52; only 28 were 65 or older. Non-stroke lesions were found in seven patients and were predicted by a recent history of convulsions (p less than 0.0001). Five lesions (four subdural haematomas and one cerebral cysticercosis) were remediable. Hypertension was present in 27 (93%) of the 29 patients with cerebral haemorrhage and in 49 (53%) of the 93 patients with stroke lesions. In 22 (45%) of these patients the hypertension had not been diagnosed, and another 22 had defaulted from treatment. All 13 patients who died before computed tomography had hypertension, and over half showed evidence of haemorrhagic stroke. There was a cardiac source for all 12 cases of cerebral embolism. In eight of the 100 patients cerebral infarction was attributed to neurosyphilis. None of the patients had clinical evidence of atherosclerosis. Smoking and oral contraceptives did not seem important risk factors for stroke. Detection and control of hypertension remain the most important measures needed to reduce the incidence of and mortality from stroke in Zimbabwe. PMID- 3087560 TI - Current clinical laboratory practice: investigation of plasma lipids--which tests and when? AB - Clinical interest in the lipoproteins stems mainly from the association between serum cholesterol concentrations and coronary heart disease. Investigations of lipoproteins should be performed in patients with premature coronary heart disease, with a strong family history of coronary heart disease, or with certain cutaneous stigmata of hyperlipoproteinaemia and when fasting serum samples are seen to be lipaemic. Family studies should be performed in appropriate cases to identify relatives at increased risk of developing coronary heart disease. Patients with conditions known to cause secondary hyperlipoproteinaemia should be investigated if they fall into one of these categories but only after treatment of the underlying condition. Non-specialist laboratories should be able to measure total cholesterol and triglyceride concentrations and high density lipoprotein cholesterol concentrations. Lipoprotein electrophoresis has a limited role in such laboratories and is not necessary as a routine procedure. Specialist laboratories should in addition be able to measure individual lipoproteins and identify apolipoprotein E phenotypes. PMID- 3087561 TI - Report from the PHLS Communicable Disease Surveillance Centre. PMID- 3087562 TI - ABC of resuscitation. Resuscitation at birth. PMID- 3087563 TI - Primary hypothyroidism presenting as amenorrhoea and galactorrhoea with hyperprolactinaemia and pituitary enlargement. PMID- 3087564 TI - Drugs in developing countries. PMID- 3087565 TI - Short term high doses of etidronate in Paget's disease of bone. PMID- 3087566 TI - Systemic steroids in chronic severe asthma. PMID- 3087567 TI - Immune changes associated with insulin dependent diabetes may remit without causing the disease: a study in identical twins. PMID- 3087568 TI - Emergencies at sea. PMID- 3087569 TI - Low serum C4 concentrations and peripheral neuropathy in type I and type II diabetes. PMID- 3087570 TI - Myoclonus epilepsy in two brothers. Clinical features and neuropathology of a unique syndrome. AB - We report 2 brothers with progressive ataxia, seizures, myoclonus, supranuclear ophthalmoplegia, progressive visual loss and embolic strokes. The epilepsy and myoclonus came on many years after the onset of the ataxia. In the more severely affected brother the myoclonus was often unilateral and focal but ultimately involved both sides of the body. His sibling had only unilateral myoclonus after a contralateral middle cerebral artery stroke. When focal, persistent and unilateral, the myoclonus in both brothers was clinically similar to epilepsia partialis continua except that muscles of the trunk and proximal limbs were the most affected. It was exacerbated by movement of the affected part but was otherwise not stimulus sensitive. The more severely affected brother had a pigmentary retinopathy and a cardiac fibromyxoid valvulopathy. In his sibling, visual loss was not fully investigated and the heart was not examined at autopsy though he had a longstanding heart murmur. Neuropathological studies showed pancerebellar cortical atrophy, cell loss in the inferior olivary nuclei and old right middle cerebral artery infarctions in both brothers. Biochemical assays for known metabolic diseases were negative. We suggest that this syndrome represents a unique autosomal recessive form of progressive myoclonus epilepsy of unclear aetiology. It is distinguished from other familial myoclonus epilepsies by the presence of early onset cerebellar ataxia, supranuclear ophthalmoplegia, pigmentary retinopathy and possibly cardiac valvulopathy with subsequent cerebral emboli. PMID- 3087571 TI - Dominantly inherited cardioskeletal myopathy with lysosomal glycogen storage and normal acid maltase levels. AB - A family is presented in which 7 members over 3 generations were affected by cardioskeletal myopathy. A vacuolar myopathy with excessive free and intralysosomal glycogen storage in skeletal and cardiac striated muscle was identified in biopsy studies. Post-mortem studies in several patients revealed changes of a congestive cardiomyopathy with myocardial fibrosis. Acid maltase, phosphorylase, debrancher and lysosomal enzyme screens, and glycolytic enzyme levels in skeletal muscle, were normal in 1 case. This is the third report of non acid maltase deficient lysosomal glycogen storage disease and adds to previous reports with the presentation of detailed family studies, examined of ante- and post-mortem cardiac histology and reports of detailed glycolytic and lysosomal enzyme analysis. This syndrome is unusual among glycogenoses in having a dominant inheritance pattern. PMID- 3087572 TI - Production and characterization of polyclonal and monoclonal antibodies to rat brain L-glutamate decarboxylase. AB - Specific monoclonal and polyclonal antibodies to rat brain glutamate decarboxylase (GAD) were produced and characterized. Polyclonal antibodies against GAD were raised in rabbits by injecting a total of 70-210 micrograms of purified GAD i.m. The specificity of anti-GAD serum was established from a variety of tests including Ouchterlony immunodiffusion, immunoelectrophoresis, immunoprecipitation, dot immunoassay, ELISA tests and Western immunoblottings. In immunodiffusion and immunoelectrophoresis tests using partially purified GAD preparations and anti-GAD serum a single, sharp precipitin line corresponding to GAD activity was obtained. Quantitative immunoprecipitation of GAD activity was achieved using anti-GAD IgG and Staphylococcus aureus. Specificity of the antiserum was further indicated from a dot immunoassay and ELISA tests in which the intensity of the reaction product was proportional to the amount of GAD protein present. In the Western immunoblotting experiments using partially purified GAD preparations only two protein bands corresponding to the position of the two subunits of GAD were stained by anti-GAD IgG, further supporting the specificity of polyclonal antibodies against GAD. In addition to polyclonal antibodies, several specific GAD-antibodies-producing clones were also obtained by the hybridoma technique. The specificity of monoclonal antibodies against GAD were established from the following criteria: positive on ELISA test using homogeneous GAD as antigen; formation of GAD--anti-GAD IgG complex as indicated from gel filtration chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis; and specific recognition of GAD subunit in a partially purified GAD preparation in Western immunoblotting test. Monoclonal antibodies were further characterized by immunohistochemical localization of known GABAergic neurons and their processes in the cerebellum and retina. PMID- 3087574 TI - Innervation of the nucleus of the solitary tract and the dorsal vagal nucleus by thyrotropin-releasing hormone-containing raphe neurons. AB - The nucleus of the solitary tract and the dorsal vagal nucleus are richly innervated by thyrotropin-releasing hormone (TRH)-containing fibers arising from the caudal raphe nuclei. After transection of vertically oriented fibers by a horizontal knife-cut in the medulla oblongata, TRH-staining disappeared from the vagal nuclei while it increased in transected nerve fibers ventral to the knife cut. TRH-containing cells are mainly located in the nucleus raphe pallidus and raphe obscurus. TRH-containing fibers run dorsally within the raphe and enter the dorsal vagal complex at its rostral tip. Then they turn caudally and send branches laterally. Immediately caudal to the level of the obex, several TRH containing fibers cross over the central canal. Cells in regions other than the raphe (hypothalamus or other rostral areas, ventrolateral medulla, cranial nerves) must contribute little to the TRH innervation of the nucleus of the solitary tract and dorsal vagal nucleus, since various knife-cuts transecting all above possible connections did not alter the TRH innervation pattern or TRH concentrations of these vagal nuclei. PMID- 3087573 TI - Brainstem localization of a thyrotropin-releasing hormone-induced change in respiratory function. AB - When rats received microinjections of 100 ng thyrotropin-releasing hormone (TRH) into the medial portions of the nucleus tractus solitarius and 12th nucleus or raphe obscurus, at the level of the obex, a significant decrease in the inspiratory time was found. Examination of TRH immunocytochemistry revealed a high density of TRH-positive nerve terminals in these regions, especially the more caudal aspects. If serotonin was depleted by neonatal 5,7 dihydroxytryptamine treatment, the respiratory response of the adults to TRH appeared potentiated. Even though the neonatal 5,7-dihydroxytryptamine reduces the occurrence of TRH-positive cell bodies, TRH-positive fibers were not appreciably altered. These results are discussed with regard to a possible role of endogenous TRH in the brainstem on rhythmic respiratory activity. PMID- 3087575 TI - Blood flow and functional responses correlate in the ovine neural lobe. AB - Regional neurohypophyseal and cerebral blood flow were measured in 5 awake unstressed female sheep with radiolabelled microspheres before and after the intracarotid infusion of a 3% NaCl solution. Plasma arginine vasopressin (AVP) levels were concurrently measured by radioimmunoassay. Following intracarotid sodium chloride infusion, neural lobe (but not median eminence) blood flow significantly increased, as did plasma AVP levels. Directed thirst and water seeking behavior was observed, accompanied by a global increase in cortical blood flow. We conclude that the neuroendocrine response and the behavioral display induced by intracarotid sodium chloride infusion are accompanied by increases in blood flow in selected brain regions. PMID- 3087576 TI - Indomethacin blocks central nociceptive effects of PGF2 alpha. AB - Intrathecal administration of PGE2 and PGF2 alpha and intradermal administration of PGE2 but not PGF2 alpha, in low doses, produce hyperalgesia as measured by the Randall-Selitto paw-withdrawal test. Indomethacin (2 mg/kg, i.p.) prevented intrathecal PGF2 alpha, but not PGE2-induced hyperalgesia. We propose that the central nociceptive effects of PGF2 alpha are mediated, indirectly, by effecting the cyclo-oxygenation of arachidonic acid in the central nervous system. PMID- 3087577 TI - Synthesis and release of catecholamines by the cat carotid body in vitro: effects of hypoxic stimulation. AB - The role of catecholamines (CAs) in cat carotid body chemoreception has been controversial. On the basis of pharmacological experiments, it would appear that endogenous dopamine (DA) may act either as an inhibitory or excitatory transmitter. Neurochemical studies on the effects of natural stimulation on the release of carotid body CAs in the cat have also been inconclusive. In the present study, we have characterized the synthesis and release of CAs in the in vitro cat carotid body preparation in response to different levels of hypoxic stimulation and have correlated these measures with the chemosensory activity of the carotid sinus nerve. The synthesis of [3H]DA and [3H]norepinephrine was linear for at least 4 h in carotid bodies incubated with their natural precursor [3H]tyrosine. Synthesis of both [3H]CAs plateaued when the [3H]tyrosine concentration in the media reached 40 microM, which is a concentration similar to that found in cat plasma. Exposure of the animals to an atmosphere of 10% O2 in N2 for 3 h prior to removal and incubation of the carotid bodies with [3H]tyrosine resulted in an approximately 100% increase in the rate of [3H]DA synthesis but no change in [3H]norepinephrine synthesis. This selective increase in [3H]DA synthesis was not detected when [3H]dihydroxyphenylalanine was used as precursor. Carotid bodies first incubated with [3H]tyrosine and later superfused with solutions equilibrated with different gas mixtures (0-100% O2 in N2) exhibited an increase in [3H]DA release and carotid sinus nerve discharge which were inversely related to the oxygen concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087578 TI - Fetal noradrenergic transplants into amine-depleted basal forebrain nuclei restore drinking to angiotensin. AB - 6-Hydroxydopamine-induced catecholamine denervations in the organum vasculosum of the lamina terminalis and the median preoptic nucleus attenuate drinking responses to systemic angiotensin II (ANG II) injections. Transplanting catecholamines in these nuclei using fetal noradrenergic (NE) cell suspension restores ANG II-elicited thirst. These results emphasize the functional importance of NE neuronal systems in nuclei of the anteroventral third ventricle (AV3V) in mediating ANG II-induced drinking behaviors. PMID- 3087579 TI - Regulation of mating behaviour in the female rat by gonadotropin-releasing hormone in the ventral tegmental area: effects of selective destruction of the A10 dopamine neurones. AB - Microinfusions of gonadotropin-releasing hormone (GnRH) into the ventral tegmental area (VTA) potentiated lordosis behaviour in oestrogen-primed ovariectomised female rats. Facilitation was observed within 5 min after the infusion and lasted for about 90 min. When GnRH was infused into the VTA of oestrogen-primed animals which were previously subjected to 6-hydroxydopamine treatment (to destroy the A10 dopamine cells), it produced a marked facilitation of lordosis lasting for about 24 h. These results suggest that the A10 dopamine neurones in the VTA may be critically involved in the mechanisms by which GnRH may modulate midbrain circuits involved in the regulation of lordosis behaviour in the female rat. The lesion studies also imply that the A10 dopamine neurones function as inhibitory neurones regulating lordosis behaviour by suppressing the activity of those cells in the VTA which are sensitive to GnRH. Removal of this inhibitory input leads to an exaggerated response. PMID- 3087581 TI - Simultaneous measurement of dopamine release and rotational behaviour in 6 hydroxydopamine denervated rats using intracerebral dialysis. AB - Amphetamine- and L-DOPA-induced changes in extracellular levels of striatal dopamine (DA) were monitored during rotational behaviour in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal DA pathway. In vivo DA release measurements were obtained using intracerebral dialysis combined with high-performance liquid chromatography with electrochemical detection (HPLC ED). In unilaterally denervated rats no DA was detected in dialysates collected from the striatum ipsilateral to the lesion while the contralateral side showed a compensatory increase in basal DA levels when compared to non-lesioned controls. Amphetamine (0.5-5.0 mg/kg s.c.) caused a dose-dependent release of DA in the striatum of normal rats and in the intact striatum of DA denervated rats but did not significantly release DA in the lesioned striatum. In response to amphetamine (0.5-5.0 mg/kg s.c.) lesioned animals showed dose-related ipsilateral rotational behaviour which in general correlated well with the time-course change in, and the total amount of, DA release in striatum contralateral to the lesion. In contrast to amphetamine, in lesioned rats, the DA precursor L-DOPA (20 mg/kg s.c.) induced readily detectable amounts of DA in dialysates collected from the DA denervated striatum. The L-DOPA-induced appearance of DA, which approached basal DA levels seen on the intact side, was concomitant with contralateral rotational behaviour. However, the time-course change in DA levels did not closely correlate with the apparently two-peak pattern of contralateral rotation induced by L-DOPA. PMID- 3087580 TI - Spinal cord noradrenergic neurons are activated in hypotension. AB - Although norepinephrine-containing nerve terminals in the spinal cord synapse in the vicinity of sympathetic preganglionic cells, their effect on sympathetic outflow has remained unclear. Since survival during hypotension necessitates sustaining maximal sympathetic activity, we used experimental hypotension as a physiological stimulus to determine whether such activity is associated with an increase or a decrease in spinal cord norepinephrine turnover. Male Sprague Dawley rats (500 g) were anesthetized with chloralose and urethane and their left carotid arteries were cannulated for blood pressure measurements and blood removal. Control animals remained normotensive during the 1-h study period; hypotensive animals were bled to a 50 mm Hg systolic pressure. Catecholamine release, as indicated by methoxyhydroxyphenylethyleneglycol sulfate (MHPG-SO4) concentrations, was greater in spinal cords of hypotensive rats than in normotensive controls. Apparent catecholamine synthesis also increased: norepinephrine concentrations did not change even though those of MHPG-SO4 doubled and the accumulation of dihydroxyphenylalanine (in other animals pretreated with NSD 1015) also doubled. These studies show that catecholamine containing neurons in the spinal cord are stimulated in hypotension, and suggest that they may function physiologically to increase sympathetic outflow and thus blood pressure. PMID- 3087582 TI - Learning impairment following lesion of the basal nucleus of Meynert in the marmoset: modification by cholinergic drugs. AB - Five common marmosets (Callithrix jacchus) received unilateral ibotenic acid lesions of the basal nucleus of Meynert (nBM). Seven days later, choline acetyltransferase activity was significantly reduced by 50% in the frontal and temporal neocortex, 40% in the amygdala, and approximately 30% in the motor, parietal and occipital cortex in the ipsilateral hemisphere. Four marmosets receiving equivalent bilateral ibotenic acid lesions were severely impaired on new visual object discrimination learning and on relearning an object discrimination learnt prior to surgery when compared with operated controls. New learning in lesioned animals was substantially improved by i.m. administration of the cholinergic agonist arecoline. Lesioned animals' learning ability improved with time but these animals were then differentially sensitive to the disruptive effect of scopolamine on discrimination learning. These results show that lesions of the nBM which destroy the rising cholinergic pathways impair learning ability but that this ability can be substantially restored by administration of a cholinergic agonist. PMID- 3087583 TI - Short-term effects of dopamine-depleting brain lesions on spontaneous activity of striatal neurons: relation to local dopamine concentration and behavior. AB - The spontaneous activity of striatal neurons was measured after dopamine (DA) depleting brain lesions were produced in rats by the neurotoxin 6 hydroxydopamine. The extent of DA depletion was determined using tissue punches from the same regions of striatum in which cell activity was recorded. Results showed that the spontaneous activity of Type II neurons in either the medial or lateral striatum increased only when local DA depletions exceeded 90%; when local depletions were less than 90%, spontaneous firing rates of Type II neurons were equivalent to control values. This finding was consistent with additional observations that ingestive and motor behaviors of the same animals were not disrupted until striatal DA depletions exceeded 90%. It also was found that spontaneous firing rates of neurons in the lateral but not the medial striatum could be at control levels in animals clearly exhibiting aphagia, adipsia and akinesia. PMID- 3087584 TI - Effects of intraventricular 6-hydroxydopamine on the dopaminergic innervation of striatum: histochemical and neurochemical analysis. AB - The impact of intracerebroventricular administration of 6-hydroxydopamine (6-HDA) on the dopamine (DA)-containing nigrostriatal projection was determined by regional histochemical and biochemical analyses. One week postinjection, we observed that tyrosine hydroxylase (TH)-positive terminals were almost completely absent from the medial portion of striatum but gradually increased in density toward the lateral margin of this structure. A similar gradient was indicated by fluorescence histochemistry and biochemical analyses of DA. In contrast, the 6 HDA-induced changes in TH activity and in dihydroxyphenylacetic acid content were less severe and showed little or no medial-to-lateral gradient. These high levels of TH activity and DOPAC content, relative to local DA concentrations, suggest an increase in the synthesis and release of DA from residual terminals that may serve to compensate for the brain damage. By 4 months postlesion, both histochemical and biochemical analyses indicated the presence of more DA terminals in striatum than there had been one week postlesion. This change was most markedly obvious in the medial striatum, which had been almost completely devoid of terminals at one week postlesion. Retrograde tracing experiments revealed that terminals appearing in the medial striatum at 4 months postlesion arise from the same region of the substantia nigra that innervates the medial striatum in the intact animal. Thus, no change in the topographic relation between substantia nigra and striatum occurred as a result of the lesion. PMID- 3087585 TI - The effects of the cholecystokinin antagonist, proglumide, on gonadotropin release in the rat. AB - Since cholecystokinin had manifest effects on anterior pituitary hormone secretion following its intraventricular injection in ovariectomized rats, we have evaluated the effects of the cholecystokinin antagonist, proglumide, to assess the physiologic significance of CCK in the control of gonadotropin secretion. Conscious rats of either sex were used following implantation of third ventricular and/or intravenous cannulae for the administration of proglumide. Blood samples were drawn from conscious animals at various times after the injection of the compound. In castrate female rats proglumide produced a small but significant increase in plasma LH whether administered by the intravenous or intraventricular route at the lower dose of 10 or 2 micrograms, respectively. The higher doses of 10 micrograms injected intraventricularly or 100 micrograms, injected intravenously failed to affect LH levels in these animals. In contrast there was a much larger increase in plasma LH in castrate males following intraventricular or intravenous injection of the lower doses of proglumide. Even after the higher doses, there was a slight increase in levels of LH by either route of injection. The results indicate that in the castrate animal proglumide can elevate LH levels by either route of injection but that the response is greater in castrate males than females. The reduction in response with the higher doses may reflect an agonist activity of proglumide. By contrast proglumide had no effect on plasma FSH except for a slight elevation observed following the intravenous or intraventricular injection of the lower doses of the compound in castrate males. The results favor a physiologically significant role of CCK in control of LH release in the rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087586 TI - Early enteral nutrition for mass burn injury: the revised egg-rich diet. AB - An aggressive enteral nutritional approach has been employed to support our severely burned patients. The diet is based on a daily intake of 5 eggs/10 kg of body weight, incorporated into milkshakes. Twelve patients with severe burns (age, 24 +/- 4 years; burns, 54 +/- 12 per cent of total body surface area (TBSA] were studied. Enteral feeding was initiated on the day of injury and gradually reached the full formula within 3-7 days. Feeding was carried out either orally or through a nasogastric drip or a combination of both, depending on the patient's condition. Each bottle of milkshake contained 2318 kJ, 29 g protein, 51 g carbohydrate and 28.6 g fat in 250 ml. Each millilitre of the diet contained 9.32 kJ. The protein provided 21 per cent of the total calorie intake, while the fat and carbohydrate provided 42 per cent and 37 per cent respectively. The mean daily intake consisted of protein (5 +/- 1.5 g/kg), carbohydrate (8 +/- 0.75 g/kg) and fat (5 +/- 1 g/kg), providing a daily administration of 378-420 kJ/kg. Plasma lipids remained within normal limits during the 40 days of the diet, while serum protein levels rose to normal levels within the first 3 weeks. PMID- 3087587 TI - [Existence of transferrin polymorphism in a species of sturgeon from the Caspian Sea: Acipenser stellatus]. AB - Though various subdivisions have been proposed in literature for species of sturgeon from the Caspian Sea, these subdivisions still remain hypothetical. Research on the erythrocyte antigens of four species of anadrome sturgeons, caught off the Iranian coast has not evidenced any erythrocyte antigenic differentiations among these four species. After marking serum with 59Fe, doing paper and starch electrophoreses and revealing the marked serum proteins by autoradiography, we have shown that a transferrin polymorphism exists in Acipenser stellatus. This isotopic marking also enabled us to identify by starch electrophoresis marked proteins corresponding to transferrins in the serum of three other species of sturgeon: Acipenser guldenstadti, Acipenser nudiventris and Huso huso. It has not however been possible to determine with certainty the existence of a transferrin polymorphism in these three species. PMID- 3087588 TI - [Respiratory ultradian variations of mean and low frequencies (from 2-80 cycles per day) in premature human infants]. AB - Oxygen consumption (VO2) and carbon dioxide production (VCO2) were continuously measured in premature human (mean gestation age of 31 weeks at birth), nursed in incubators within a neutral thermal environment and submitted to a continuous lighting. At a mean postnatal age of 30 days, and for a mean body weight of 1.8 kg, spectral analysis shows VO2 and VCO2 ultradian variations of mean and low frequencies (2 less than f less than 80 c.day--1; i.e. periods 12 greater than t greater than 0.3 hr). It is hypothesized that these periodic variations can be compared to those previously evidenced in small laboratory vertebrates and in macaques. PMID- 3087589 TI - [Production of IL2 and induction of IL2 receptor: two independent and dissociable events during allogenic stimulation in vitro in man]. AB - Donors from HLA genotyped families are extremely useful for immunogenetic studies. Analysis of the in vitro allogenic response of lymphocytes from HLA recombinant siblings can dissect the respective role of HLA class I and class II antigens for the lymphocyte activation. Using lymphocytes from such donors, we have demonstrated that IL2 production is triggered by HLA class II disparities (but not by HLA class I), HLA class I disparities can prime the cytotoxic T lymphocytes precursors inducing the IL2 receptor on the specific clones which will proliferate in presence of IL2 either from endogenous origin (in the case of HLA class II disparities) or from experimentally added IL2 in the culture. PMID- 3087590 TI - [Diagnosis of cellular respiratory arrest by NADH laser fluorimetry. Applications in heart surgery and in experimental pharmacology]. AB - The continuous measurement of intratissular NADH concentration allows early detection of cellular respiration arrest during clinical situations, i.e. allows a non-destructive, in situ, continuous measurement of ATP formation. This detection enables the physician or surgeon to intervene during a phase of cellular respiration arrest, before structural cellular alterations occur, thereby preventing potential tissular necrosis. The method has now been validated in experimental cardiac surgery for the monitoring of myocardial preservation techniques during cardiopulmonary by-pass, and in cardiac pharmacology, for analysis of drugs' effects on myocardial energetic metabolism. Its industrial development is currently under way. Preliminary investigation strongly suggests the vast potential of this diagnostic method in both clinical and experimental fields. PMID- 3087591 TI - [Coupled excitation and contraction in skeletal muscles: arguments in favor of a mechanism implicating inositol metabolism]. AB - When mouse diaphragms are incubated in vitro with [14C] inositol, radioactivity is observed at post synaptic areas in phosphatidyl-inositols and in inositol phosphates. Synaptic desensitization suppresses the labelled inositol-phosphates. Lindane restores the labelling effect without suppressing the desensitized state. PMID- 3087592 TI - [Effect of newborn rat testes on the male sexual behavior of the testosterone treated adult]. AB - Neonatal male rats were castrated either at 0, 6 or 24 hrs. after birth. As adults, testosterone was delivered by subcutaneous implantation of a Silastic capsule containing this hormone. The probability to display mounting behavior in presence of an estrous female was lower when the animals were castrated at 0 hr. than at 6 or 24 hrs. or when they received a subcutaneous injection of 1 microgram of testosterone propionate, at the time of castration at 0 hr. These results suggest that in the rat, during the 6 hrs. following birth, neonatal testes influence the sensitivity of the adult central nervous system to testosterone. PMID- 3087593 TI - [Mathematical model for an evolutive and hierarchical living system, based on the theory of categories]. AB - The notion of an evolutive hierarchical system proposed here retains the following characteristics of some natural systems, like living organisms: they have an internal organization consisting of more or less complex components with interrelations; they maintain their organization in time although their components are changing; they may be studied at several complexity levels (e.g., molecular, cellular, ...). The idea is to model the state of the system at a given instant by a category, the state transition by a functor, a complex object by the (direct) limit of a pattern of linked objects (its own organization). The emergence of new properties for a complex object is measured, and a development process is described. PMID- 3087594 TI - [Ultrastructural detection of messenger RNA coding for growth hormone in the rat anterior pituitary by in situ hybridization]. AB - Ultrastructural detection of the messenger RNA coding for growth hormone in rat pituitary gland could be obtained by association of in situ hybridization and cryoultramicrotomy. Messenger RNAs were localized in the anterior pituitary gland. Silver grain densities observed in autoradiograms after in situ hybridization were dependent to incubation period and to fixation. It was necessary to determine a compromise between ultrastructural aspect and silver grain densities. Messenger RNAs were detected in somatotropic cells, identified by ultrastructural characteristics, in both the nucleus (euchromatin and nuclear membrane) and cytoplasm, in vicinity to endoplasmic reticulum. PMID- 3087596 TI - [Repeated bronchial fiberscopy in a young girl with cystic fibrosis. Anesthetic problems]. PMID- 3087595 TI - [Controlled hypotension during posterior vertebral arthrodesis; value of an isoflurane-nitroglycerin combination]. AB - Eighteen young patients (mean age +/- SD 15.9 +/- 3.3) scheduled for operative treatment of idiopathic scoliosis (posterior spine fusion) were studied during surgery. Deliberate hypotension (MAP less than 60 mm Hg) of long duration (greater than 2 hours) was induced using isoflurane and nitroglycerin. Hypotension was effective in less than 15 min in all patients. The mean inspiratory fraction of isoflurane employed was 2.04 +/- 0.19% for the first operative hour, and 1.36 +/- 0.20% for the second operative hour. The difference between these inspiratory fractions is highly significant (p less than 0.001), while the rate of nitroglycerin infusion was unchanged (3 micrograms X kg-1 X min 1). Heart rate increases significantly at H1 and H2 when compared to preinduction values and the product of heart rate X systolic blood pressure decreases significantly with a mean of 30% versus preinduction values. A satisfactory operative field was obtained in all cases. Blood loss was dependent of the duration of surgery, of the total blood volume of the patient, of the length of spine fusion. For each patient, a slope of blood loss was established. The mean slope was 3.74 +/- 0.39 ml X kg-1 X h-1. The determination of the slope at the end of the first operative hour allows us to predict the total blood loss during surgery. Intra operative awakening was obtained 22.8 +/- 3.7 min after isoflurane was discontinued. Isoflurane and nitroglycerin produce a stable and safe hypotension with no major hemodynamic disturbances. Isoflurane has to be discontinued 20 min before the wake-up test. PMID- 3087598 TI - Differentiation of osteoid-producing cells in vitro: possible evidence for the requirement of a microenvironment. AB - Periostea were dissected from 17-day-old chicken embryo calvariae, placed on millipore filters, and cultured on fluid media containing serum or on serum and plasma containing "plasma clots," in three ways: 1) with the osteogenic layer facing the filter, 2) with the osteogenic layer away from the filter, 3) folded such that the osteogenic layer was in apposition with itself within the fold. The cultures were studied histologically as well as biochemically. Periostea that were cultured folded showed differentiation of osteoblastlike cells after 2 days, and production of osteoid at day 4. Tissues cultured with the osteogenic layer away from the filter demonstrated similar osteoblastic differentiation and osteoid production. Both types of cultures exhibited an increase in histochemically detectable alkaline phosphatase activity over the 4 day culture period that was associated with osteoblasts and the osteogenic area. Periostea cultured with the osteogenic layer facing the filter produced no osteoid. In these cultures, histochemically detectable alkaline phosphatase activity decreased and virtually disappeared over the 4 day culture period. The possibility that the creation of a suitable micro-environment is required for osteodifferentiation in this culture system is discussed. PMID- 3087597 TI - Age changes in the bone mineral of the lumbar spine in normal women. AB - The bone mineral content (BMC) and the bone mineral areal content (BMAC) were determined with dual-photon absorptiometry in the third lumbar vertebra in a random sample of 214 women between 35 and 80 years of age in the city of Goteborg, Sweden. A continuous aging decrease (1%/year) of both the BMC and the BMAC was noted after age 35. The rate at which bone loss occurred was similar for all age groups when analyzed by 5 year intervals. No clear acceleration of bone loss was noted around the usual time of the menopause. PMID- 3087599 TI - Evidence for osteoclast production in mixed bone cell culture. AB - Osteoclastlike cells (OLCs) were recognized by their morphological, histochemical, and behavioral characteristics. These characteristics were initially observed in freshly isolated osteoclasts when neonatal rat bone cells were introduced into culture. Epithelioid cells proliferated during the first week to form a confluent layer. The cells' alkaline phosphatase content and ability to produce elevated levels of cyclic adenosine monophosphate in response to parathyroid hormone (PTH) led us to tentatively describe them as osteoblastlike cells. When a second addition of neonatal bone cells was made onto this confluent layer, OLCs were produced, their numbers increasing to a maximum 7 days later and dying out 3 weeks later. Mononuclear cells with similar characteristics to these multinuclear OLCs were observed and their production and disappearance closely paralleled that of the OLCs. Fusion of OLCs was observed. The conditions under which OLCs were produced are described. PMID- 3087600 TI - The high affinity calcium inhibition of parathyroid adenylate cyclase is not calmodulin dependent. AB - To investigate the possible role of calmodulin in the calcium sensitivity of parathyroid adenylate cyclase (AC), the effect of the calmodulin inhibitor trifluoperazine hydrochloride (TFP) on the calcium sensitivity of forskolin stimulated AC activity was investigated in membranes prepared from normal porcine parathyroid glands. TFP inhibited AC in a concentration-dependent manner, the IC50 being approximately 100 microM. The inhibition of the enzyme occurred at roughly the same concentration of TFP in the presence and absence of calcium. Another calmodulin inhibitor, N-(6-aminohexyl)-chloro-1-naphthalenesulfonamide (W 7), also inhibited AC in a calcium-independent manner with a IC50 of approximately 200 microM. The pattern of calcium inhibition of AC was compared in membranes prewashed with either EGTA or 2 microM ionic calcium plus 100 microM TFP in an attempt to remove endogenous calmodulin. Neither treatment significantly altered the apparent affinities of the two previously reported calcium inhibition sites, nor did they alter the relative contribution of the individual calcium inhibition sites to the overall calcium inhibition. Inclusion of 100 microM TFP in the incubation mixture resulted in no change in the apparent affinities of the calcium inhibition site although it did result in a significant decrease in the relative contribution of the high affinity site (P less than 0.05). Addition of exogenous calmodulin (5-50 micrograms/ml) had no significant effect on AC. We conclude from these studies that the inhibition of parathyroid AC by calcium is independent of calmodulin and that this enzyme has intrinsic high sensitivity to calcium. PMID- 3087601 TI - Influence of glucocorticoids on calcium absorption in different segments of the rat intestine. AB - Glucocorticoids enhance the movement of fluid and sodium in the duodenum, thereby resulting in an increase in the passive transport of calcium. Since passive transport of calcium predominates in the distal intestinal segments, the influence of glucocorticoids on calcium and fluid transport in the duodenum, mid jejunum, ileum, and colon of the rat was studied. Calcium transport and fluid absorption was determined by the in vivo ligated loop technique. One segment was ligated in each animal. Under either normal osmolarity or hypertonic conditions, administration of cortisone stimulated intestinal fluid absorption in each segment of the small intestine, but not in the colon. Since the final fluid sodium concentration was not altered, cortisone enhanced net sodium absorption in proportion to the increase in fluid transport. Glucocorticoids inhibited the active transport of calcium in the proximal regions of the small intestine by bidirectional changes in calcium flux. However, the inhibitory effect was not apparent under the conditions where passive transport predominates. The stimulation of passive transport in the mid-jejunum overcomes the inhibition of active transport. In the ileal region, glucocorticoids increased active transport of calcium by 165%, whereas the enhancement of calcium transport under conditions where passive transport predominated reached 217%. This result indicates that both active and passive transport of calcium were enhanced by glucocorticoid treatment. In the colon, glucocorticoids increased active transport by 170%. However, the magnitude of the increase in calcium transport was less under conditions where passive transport predominates (129%), indicating that glucocorticoids stimulate the active transport of calcium in the colon with no appreciable stimulation of passive transport. PMID- 3087602 TI - Effect of calcium deprivation on rat dams on fetuses and newborn offspring. AB - Calcium-deficient rats were put to breeding, and fetuses and offsprings were collected at 18 days in utero, at birth, and at 5-10 days post partum. Furthermore, blood and milk were collected from the dams, and blood from the offsprings. The rat pups had normal weights at 18 days in utero and at birth, whereas at 5-10 days post partum the growth was significantly reduced. The relative amount of total solids in the body was also decreased at 5 and 10 days post partum (increased water content). Despite the fact that serum Ca in the dams was severely reduced, the calcium content in the serum of the offspring was only moderately lowered, and there was no correlation between serum Ca in dams and offspring. The content of total solids in the rat milk was increased, whereas the calcium content remained unchanged. The body content of Ca and P in the rat pups was decreased only at 5 and 10 days post partum. The degree of reduction was nearly the same for all these elements, amounting to 15-19% at 5 days post partum and 38-40% at 10 days post partum. If, however, the content of the elements was calculated as percentage of total body solids, a significant increase was found for all of them at 5 and 10 days post partum. Significant differences in Ca:P ratios were not found at any age. PMID- 3087603 TI - The uptake of lithium ions by synthetic carbonated hydroxyapatite. AB - Carbonated hydroxyapatites in the presence of F- and Li+ were synthesized. Limited uptake (0.2-1.6 ppm) of Li+ by the apatites was observed, which was proportional to the initially added Li+ and the carbonate concentration of the samples. Fluoride has retarding effect on the Li+ uptake. Li+ causes a decrease in the solubility of carbonated hydroxyapatite. PMID- 3087605 TI - The assessment of intestinal calcium absorption using stable strontium. AB - The availability of currently used methods of measuring intestinal calcium absorption is limited by their expense and complexity. Since this measurement may be important in selecting appropriate therapies for patients with osteoporosis, a simpler procedure is required. This paper describes a test which measures the intestinal absorption of stable strontium. A comparison of this test with the single-isotope radio-calcium absorption test in the same group of patients showed a close correlation between the fractional absorption rates of the two elements (r = 0.93, P less than 0.001). Subjects were correctly categorized as having normal or low absorption in 12 out of 13 cases (92%) and the value in the misclassified subject was at the borderline between normal and low calcium absorption. The convenience, low cost, and freedom from radioactivity of stable strontium make it suitable for routine clinical use and, if necessary, repeated testing. If these early results are confirmed, this test will make the assessment of calcium absorption much more widely available. PMID- 3087604 TI - Alkaline phosphatase inhibition by levamisole prevents 1,25-dihydroxyvitamin D3 stimulated bone mineralization in the mouse. AB - To determine the relationship between alkaline phosphatase (AP), 1,25(OD)2D3 and bone formation in vivo, we have examined the effects of levamisole, a stereospecific inhibitor of AP on bone formation and on 1,25(OH)2D3-stimulated bone mineralization in the mouse. Normal mice were injected daily with levamisole at doses of 40 and 80 mg/kg/b.w. The compound was given alone or in combination with 1,25(OH)2D3 infusion (0.05 micrograms/kg/d) for 7 days. Treatment with levamisole alone inhibited the serum AP activity (mainly of skeletal origin in mice) by 18.4 and 61.3% for the low and high dose respectively. No deleterious effect on body growth, tibia length, and bone cells population was detected. The moderate inhibition of AP activity produced by the lower dose of levamisole alone (18.4%) or in combination with 1,25(OH)2D3 (37.9%) was associated with a reduced endosteal matrix apposition rate (MaAR) determined by double 3H-proline labeling method. This effect was related to a levamisole-induced fall in serum phosphate. Despite the moderate inhibition of AP activity, the mineral apposition rate (MiAR) determined by the double tetracycline labeling method remained normal. Moreover, 1,25(OH)2D3 infusion still resulted in increased MiAR which was stimulated to the same extent as in the absence of levamisole. By contrast, the more severe inhibition of AP activity induced by 80 mg/kg of levamisole alone (61.3%) or in combination with 1,25(OH)2D3 (45.8%) inhibited both the MaAR and the MiAR and prevented the stimulatory effect of 1,25(OH)2D3 on bone mineralization. The data show that AP activity affects the bone matrix and mineral apposition rates in vivo and that severe inhibition of AP activity inhibits the 1,25(OH)2D3-induced stimulation of bone mineralization in the mouse. PMID- 3087606 TI - Intraoperative events diagnosed by expired carbon dioxide monitoring in children. AB - Expired carbon dioxide measurements (PeCO2) were used (1) to assess the adequacy of initial alveolar ventilation, and (2) to document intraoperative airway events and metabolic trends. Three hundred and thirty-one children were studied. Thirty five intraoperative events were diagnosed by continuous PeCO2 monitoring; 20 were potentially life-threatening problems (malignant hyperthermia, circuit disconnection or leak, equipment failure, accidental extubation, endobronchial intubation, or kinked tube); only two of these were also diagnosed clinically. The duration of anaesthesia may be a factor: 3.9 hours for cases with events vs. 2.5 hours for cases without events (p less than 0.002). There was a higher incidence of hypercarbia (peak expired PeCO2 greater than or equal to 50) in children who were not intubated (29 per cent) compared to those who had an endotracheal tube in place (12 per cent) (p = 0.0001). Hypocarbia (peak expired PeCO2 less than or equal to 30) was more frequent in intubated cases (11 per cent) than in unintubated cases (three per cent) (p = 0.03). There was a high incidence of hypocarbia in infants less than one year of age (p = 0.02). We conclude: (1) life-threatening airway problems are common during anaesthesia in paediatric patients; (2) quantitative measurement of PeCO2 provides an early warning of potentially catastrophic anaesthetic mishaps; (3) the incidence of events increases with duration of anaesthesia. PMID- 3087607 TI - Arachidonic acid and acetylcholine induced relaxation of bovine coronary artery: effect of indomethacin and methylene blue. AB - Endothelial intact bovine coronary artery (BCA) rings precontracted with U46619 relax to acetylcholine (Ach) and arachidonic acid (AA). Relaxation to Ach is blocked by atropine. In an attempt to elucidate the mechanisms of these responses, we found that preincubation with methylene blue, an inhibitor of soluble guanylate cyclase activity, inhibited both Ach and AA induced relaxation. Preincubation with indomethacin had no effect on Ach induced relaxation, but partially inhibited the relaxation of endothelial intact BCA rings to AA. PMID- 3087608 TI - Plasmids associated with a phagelike particle and with a satellite inclusion in Bacillus thuringiensis ssp. israelensis. AB - Variants of Bacillus thuringiensis ssp. israelensis were isolated using a 42 degrees C plasmid curing method. Those that were missing the large toxic crystalline inclusion still possessed in their sporulated cells a small inclusion similar to the satellite inclusion of the wild type. These crystal-minus but satellite-positive variants, like the wild type, produced sporulation-dependent phagelike particles; variants lacking both the crystal and the satellite did not. These latter strains lacked both a 75 and a 68 megadalton plasmid present in the wild type. However, a crystal-positive, satellite-minus strain possessing the 75 but lacking the 68 megadalton plasmid produced the phagelike particles. Examination of recipient strains that were initially devoid of crystal, satellite, and plasmids revealed the satellite and phagelike producing characteristics could have been cotransformed with the 68 megadalton plasmid. Likewise the toxic crystal and phagelike particle producing characters could have been cotransformed into a recipient which had acquired the 75 megadalton plasmids already known to be associated with the synthesis of the crystal inclusion. Thus the gene coding for the satellite inclusion appears to reside in the 68 megadalton plasmid, while that coding for the phagelike particle can reside in either the 68 or 75 megadalton plasmid. PMID- 3087609 TI - Effect of lipopolysaccharide mutations and temperature on plasmid transformation efficiency in Pseudomonas aeruginosa. AB - We have isolated, and characterized electrophoretically, two new lipopolysaccharide-defective (rough) mutants of Pseudomonas aeruginosa strain PAO. These strains, AK1401 and AK1414, together with two previously characterized isolates, AK1012 and AK1282, were used as recipients in transformation experiments with plasmid pR01614 DNA. The roughest mutant, AK1282, was not transformable, while the transformation efficiency of AK1012, and to a lesser extent the wild-type strain, was dependent upon the growth temperature. The two new isolates which are less rough than AK1012 were transformed at a frequency equivalent to that of the wild type-strain. PMID- 3087610 TI - Antibacterial activity of BCG-induced, interferon-containing sera. AB - Sera from mice which have been vaccinated with BCG and challenged with old tuberculin contain gamma interferon. These same sera also express antibacterial activity. Using Staphylococcus aureus we demonstrated that its growth was inhibited at dilutions of sera as high as 1:320. A 4% concentration of sera reduced the growth rate of the S. aureus from 1.6 to 0.6 doubling times per hour. The activity was stable at 56 degrees C but destroyed by 80 degrees C. It was nondialysable and destroyed by acid conditions (pH 2.0) and by the proteolytic enzymes trypsin and chymotrypsin. Antibodies to gamma interferon neutralized the antiviral activity but not the antibacterial activity. Mitogen-induced and virus induced interferons did not have activity. We subsequently demonstrated that the factor could be induced in mice using BCG without the secondary old tuberculin challenge. No gamma interferon was found in the sera of mice given BCG without old tuberculin. These findings indicate that the antibacterial activity of these sera is not dependent on the presence of gamma interferon. We will continue to work to characterize and identify the antibacterial component in these sera. PMID- 3087611 TI - Optic neuritis and myelopathy in systemic lupus erythematosus. AB - The optic neuritis of systemic lupus erythematosus (S.L.E.) more frequently results in the persistence of a central scotoma or complete blindness after a single attack than demyelinating optic neuritis, although the initial clinical presentations may be identical. A significant number of patients, however, recover normal vision. Optic neuritis may be the presenting symptom of S.L.E. and as myelopathy may also occur in the course of the disease, confusion with multiple sclerosis may result, especially if there are no arthritic, cutaneous nor visceral manifestations. We report a case of lupus optic neuritis associated with anticardiolipin antibodies and a circulating lupus anticoagulant and suggest these may be a marker for vasculitic optic neuritis and play a role in its aetiology. PMID- 3087613 TI - Medical decisions in the selection of therapy for the child with cancer. AB - This paper discusses the treatment development that has taken place for children with cancer. It is argued that the physician is a coequal partner with other members of the total care team of the child. The factors that demand individualization of therapy will be discussed, and the stages in medical decision making will be reviewed. The physician is not a member of the team as a researcher, but as a medical care giver. The physician also has special knowledge. The expertise that is brought to the team by a physician must ultimately be an understanding of the pathophysiology of the disease. Once therapy is designed on pathophysiological understanding, cancer can become just another disease among the possible diseases of childhood, and medical decision making can be done rationally and eventually, to a large degree, in the hometown community. PMID- 3087612 TI - Diagnostic methods in occupational allergic lung disease. PMID- 3087614 TI - Not another fractured hip. PMID- 3087616 TI - Ergotamine tartrate dependency: features and possible mechanisms. AB - Based on our clinical experience and the data reviewed and presented in this report, we propose that a state of physical dependency to ergotamine tartrate exists. This dependency state is characterized by the irresistible and dependable use of ergotamine tartrate and is contingent upon a self-sustaining, rhythmic headache/medication cycle that reflects the dependency. The headache and accompaniments (withdrawal headache?) represent the primary withdrawal symptoms. The presence of this state appears to render patients refractory to other forms of preventative therapy, which can be effective only when ergotamine is discontinued and the cycle broken. If the condition is left untreated, it is likely though by no means certain that the more traditional aspects of ergotism will evolve, although variable susceptibility and tolerance to ergotamine tartrate have been demonstrated. The mechanism of this disorder remains uncertain but might be related to the influence of ergotamine tartrate on the limbic hypothalamic-pituitary-adrenal axis and other aminergic centers (locus ceruleus), areas considered by some as the central loci for the pathogenesis and associated symptoms of migraine. PMID- 3087615 TI - Enhancement of beta-propiolactone tumorigenesis in mouse skin by pretreatment with the anti-inflammatory steroid fluocinolone acetonide. AB - Using a two-step carcinogenesis protocol, SENCAR mice were initiated with 25 micrograms 7,12-dimethylbenz[a] anthracene (DMBA) and were then treated twice weekly with either (a) 0.5 mg beta-propiolactone (BPL) or (b) 1 microgram fluocinolone acetonide (FA) followed in 30 min by 0.5 mg BPL. The tumor incidence for the group receiving FA prior to BPL was significantly greater than for BPL alone (P less than 0.0005). Under these experimental conditions, BPL alone showed neither promoting activity nor complete carcinogenic activity. These results were not anticipated, but the reasons for their occurrence are being explored. PMID- 3087618 TI - Treatment of advanced adenocarcinoma of the kidney with ICRF-187: a Southeastern Cancer Study Group Trial. PMID- 3087617 TI - Doxorubicin, ifosfamide, and dacarbazine (AID) with mesna uroprotection for advanced untreated sarcoma: a phase I study. AB - The regimen of doxorubicin (DOX), ifosfamide (IFF), and dacarbazine (DTIC) (AID) for previously untreated inoperable or metastatic sarcoma has acceptable toxicity with significant activity. Twenty patients received 79 courses of DOX (60-75 mg/m2) with or without DTIC (900 mg/m2) by continuous infusion over 72 hours with escalating doses of IFF and mesna uroprotection. Nineteen patients were evaluable for toxicity. Myelosuppression was dose-limiting. The maximum tolerated dose was DOX at 60 mg/m2, DTIC at 900 mg/m2, and IFF at 7500 mg/m2 per course. Of the 79 courses analyzed, 33 (42%) resulted in wbc counts less than 1000/microliter; 14 (18%) were complicated by fever and neutropenia, and three by sepsis. There were no toxic deaths. Relative platelet sparing was observed and nadirs were brief. In contrast to bolus-dose DTIC divided over 5 days, DTIC by continuous infusion did not add significantly to gastrointestinal toxicity. Nausea and vomiting was well controlled by antiemetics. Mucositis occurred sporadically. Unlike our phase II study of IFF alone, no CNS or renal toxicity was observed. No cardiac toxicity was encountered, although only four patients have received greater than 450 mg/m2 of cumulative DOX. One episode of DOX extravasation occurred despite a long iv line that extended to the axilla. No serious tissue damage was observed, perhaps due to the dilute solutions of DOX used. Partial responses were seen in eight of 18 evaluable patients (44%) and in six of 11 patients at or near the phase II level. Two additional patients with minimal response have continued tumor regression. The median number of courses before partial response was four (range, one to five). The median duration of response has not been reached (3+ to 10+ months). An inoperable primary has been rendered surgically resectable in one patient. Activity in previously untreated sarcomas should be further evaluated in a randomized phase III study against a standard DOX-containing combination. PMID- 3087620 TI - Effect of oral penicillin on pneumococcal carriage in elderly men with chronic bronchitis. AB - A double-blind, randomized, placebo-controlled trial was undertaken to evaluate the effect of penicillin on the pneumococcal carrier state of 32 men with chronic bronchitis. Treatment consisted of 250-mg phenoxymethyl penicillin or placebo tablets taken by mouth twice daily for periods of one to three years. Penicillin eradicated Streptococcus pneumoniae from the respiratory tracts of all carriers and prevented colonization with pneumococci for the duration of treatment, whereas placebo had no discernible effect on the carrier state (P = 0.0015). The conclusion is that daily penicillin orally in low doses eliminates pneumococci from the oropharynx of elderly patients with clinically stable chronic bronchitis. PMID- 3087621 TI - Synergistic activity of amikacin with aztreonam against Pseudomonas aeruginosa and other gram-negative organisms. AB - The effects of amikacin in combination with aztreonam were tested on 100 strains of gram-negative bacteria by means of the microtiter checkerboard system. Eighty one strains were Pseudomonas aeruginosa, eight were Enterobacter species, seven were Acinetobacter species, two were Alcaligenes species, one was a Citrobacter organism, and one was Pseudomonas stutzeri. All strains had a minimal inhibitory concentration (MIC) to aztreonam between 4 and 256 micrograms/ml (MIC50 = 16 micrograms/ml) and an MIC to amikacin between 8 and greater than 128 micrograms/ml (MIC50 = 16 micrograms/ml). A synergistic effect (fourfold less MIC when both aztreonam and amikacin were present) was observed for 40 (49%) of 81 P aeruginosa and three (16%) of 19 of the other strains tested. All the remaining test strains showed an additive response; no antagonism was observed. The MICs to aztreonam and to amikacin for 98% of strains that exhibited synergism ranged from 2 to 32 micrograms/ml. PMID- 3087619 TI - Randomized controlled study of postoperative adjuvant immunochemotherapy with Nocardia rubra cell wall skeleton (N-CWS) and Tegafur for gastric carcinoma. AB - We performed a randomized controlled study of postoperative adjuvant immunochemotherapy with Nocardia rubra cell wall skeleton (N-CWS) and Tegafur for gastric carcinoma between September 1979 and March 1983. A total of 309 patients were entered into this trial. Of the 309 patients, there were 98 evaluable patients in the chemotherapy group and 115 evaluable patients in the immunochemotherapy group. In both groups, Tegafur was given as chemotherapy at a daily dose of 400 to 800 mg, starting at 24-29 days after gastrectomy. In the immunochemotherapy group, 400 micrograms of N-CWS was injected i.d. within the 2nd postoperative week. It was given weekly during the first month and subsequently monthly for as long as practicable. The patients were surveyed for length of survival in March 1985. The postoperative survival rate was analyzed for all cases, and for patients with various histopathological stages of carcinoma for comparison between the two treatment groups. No statistical difference was detected between the two groups in terms of age, sex, surgical curability, or stage of carcinoma. The overall survival rate for all patients was significantly higher in the immunochemotherapy group than in the chemotherapy group (p less than 0.05). With stage III plus IV disease, 53 patients from the chemotherapy group and 61 patients from the immunochemotherapy group were included for the analysis. As a consequence, a highly significant survival rate was observed in patients with stage III plus IV carcinoma in the immunochemotherapy group (p less than 0.005) as compared to the chemotherapy group. The overall 5-year (1800 days) survival rate after surgical treatment was 60.2% for the chemotherapy group and 73.2% for the immunochemotherapy group. In patients with stage III plus IV disease, the 5-year survival rates of the two treatment groups were 28.8% and 52.4%, respectively. Accordingly, the 50% survival period of patients with stage III plus IV cancer was 1800 days or more in the immunochemotherapy group, whereas it was only 722 days in the chemotherapy group. These results emphasize the effectiveness of N-CWS as an adjuvant immunotherapeutic agent in postoperative gastric cancer patients. The main side effects of N-CWS were skin lesions in the injected sites and fever, but these were temporary and not serious. PMID- 3087622 TI - [24-hour whole-body retention of 99mTc-methylene diphosphonate as an indicator of metabolic activity in osseous tissue in osteopathies]. PMID- 3087623 TI - [Epidemiological significance of lipopolysaccharide serotyping in Neisseria meningitidis group A]. PMID- 3087624 TI - [Carriers of epidemic hemorrhagic fever virus in rodents and mites in EHF endemic area]. PMID- 3087625 TI - The period clock locus of D. melanogaster codes for a proteoglycan. AB - The period (per) gene of D. melanogaster is involved in the generation of biological rhythms. The most striking feature of the predicted coding sequence, corresponding to the key 4.5 kb transcript from this locus, is an extensive run of alternating Gly-Thr residues. This is homologous to a series of Gly-Ser repeats in a chondroitin sulfate proteoglycan. To determine whether the per transcript codes for a proteoglycan, a region of its coding sequence was expressed (in bacteria) as part of a fusion protein, which was used to immunize rabbits. When the resultant immune sera were used to probe fly protein preparations, they detected an antigen that is present in wild-type flies and absent in a per- mutant. Biochemical characterization of this antigen indicated that it is indeed a proteoglycan. PMID- 3087626 TI - Developmentally regulated rearrangement and expression of genes encoding the T cell receptor-T3 complex. AB - Human leukemic cells corresponding to the earliest identifiable stages of intrathymic T cell differentiation lack cell surface expression of the T cell receptor(TCR alpha/beta)-T3 complex but transcribe TCR beta mRNA from either germ line configuration (1/13) or partially (DJ) or fully (VDJ) rearranged (12/13) genes. These cells do not produce TCR alpha mRNA, but do contain T3 delta and T3 epsilon mRNA and accumulate T3 polypeptides, primarily in the perinuclear envelope. Equivalent normal T cells isolated from thymus have a predominantly germ-line configuration of TCR beta but contain intracellular T3 proteins. T3 gene expression is therefore a very early event in T cell differentiation. TCR alpha chain production appears to be the limiting maturation-linked event in the transport, assembly, and cell surface membrane insertion of the TCR alpha/beta-T3 complex. PMID- 3087627 TI - Inducible secretion of large, biologically potent von Willebrand factor multimers. AB - von Willebrand factor (vWf) secreted constitutively by human endothelial cells was compared to that released from Weibel-Palade bodies after stimulation. The majority of constitutively secreted molecules were dimeric and contained both pro vWf and mature subunits. In contrast, the vWf released by the calcium ionophore A23187 or thrombin consisted of only very large multimers of mature subunits. The large multimers are known to be more active in in vitro platelet binding assays, and their absence in vivo results in a bleeding disorder. Endothelial cells therefore concentrate a special subclass of very large and biologically potent vWf multimers in Weibel-Palade bodies, presumably available for release in response to vascular injury. PMID- 3087628 TI - Tandem kappa immunoglobulin promoters are equally active in the presence of the kappa enhancer: implications for models of enhancer function. AB - Transcription of immunoglobulin kappa genes is regulated by enhancer and promoter elements, both of which function in a tissue-specific fashion. We have studied the interaction of these elements by transfecting plasmacytoma cells with genes that have tandem kappa promoters located next to a single kappa enhancer and assaying these genes for transient or stable transcription. We find that the promoters located proximal and distal to the enhancer function identically whether they are separated by 440 bp or by 2.7 kb or whether they are located 1.7 or 7.7 kb away from the enhancer. Our results indicate that the immunoglobulin kappa enhancer does not operate as a bidirectional entry site for RNA polymerase or for other factors associated with the transcription complex. Rather, they suggest that the enhancer exerts its influence uniformly over large distances and independently of the presence of intervening promoters. PMID- 3087629 TI - An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. AB - We have characterized a cDNA clone that encodes a protein related to the 70 kd heat shock protein, but is expressed in normal rat liver. This protein has a hydrophobic leader and is secreted into the endoplasmic reticulum. We show that it is identical with two previously described proteins: GRP78, whose synthesis is induced by glucose starvation, and BiP, which is found bound to immunoglobulin heavy chains in pre-B cells. This protein, which is abundant in antibody secreting cells, can be released from heavy chains by ATP, a reaction analogous to the release of hsp70 from heat shocked nuclear structures. We propose a specific role for this protein in the assembly of secreted and membrane-bound proteins. PMID- 3087631 TI - [Termination of pregnancy in the 2d trimester by the modified Manstein method]. PMID- 3087630 TI - Carbonic anhydrase activity in developing sea urchin embryos with special reference to calcification of spicules. AB - Eggs and embryos of the sea urchins Anthocidaris crassispina and Hemicentrotus pulcherrimus did not exhibit significant changes in carbonic anhydrase activity during early development. Acetazolamide inhibited enzyme activity in homogenates of embryos and inhibited the formation of calcified spicules in a culture of micromeres at concentrations between 40 and 100 microM. Acetazolamide allowed intact embryos to develop to quasi-normal plutei but inhibited calcium deposition in the spicules. It is suggested that carbonic anhydrase contributes to CaCO3 deposition in the spicule. PMID- 3087632 TI - [Bioactive and immunoreactive gonadotropins]. PMID- 3087633 TI - [Characterization of TRH-degrading activity in plasma, tissue and milk]. PMID- 3087634 TI - [The TRH stimulation test in children]. PMID- 3087635 TI - [Use of the radiosaturation analysis method in the diagnosis and monitoring of viral hepatitis]. PMID- 3087636 TI - Survey of aminoglycoside resistance patterns. AB - We studied the susceptibility of 545 gram-negative clinical isolates to six aminoglycosides: gentamicin, tobramycin, netilmicin, amikacin, 2'-N ethylnetilmicin, and 6'-N-ethylnetilmicin. The resistant strains (359) have been classified into aminoglycoside resistance (patterns) phenotypes (AGRPs) corresponding to known resistance mechanisms. The results clearly demonstrated that most strains of Proteus spp., Klebsiella spp., Escherichia coli and Pseudomonas aeruginosa appeared to be able to adenylate the 2'-hydroxyl group (ANT(2'')) of aminoglycosides. Of the AGRPs reflecting acetylating activity, the AAC(3)-II and AAC(3)-I predominated. The AGRP AAC(2') was limited mainly to Proteus and Providencia isolates. It is noteworthy that permeability type resistance (PTR) was observed only among P. aeruginosa strains. Statistical evaluation of the results, using a discriminant regression analysis showed that PTR P. aeruginosa strains were isolated less often from urine than from other clinical sources (P less than 0.05). On the contrary the ANT(2'') Proteus strains were more common isolates from urinary infections as compared to those from other sources (P less than 0.05). Other correlations between frequency of AGRPs, bacterial groups, and various clinical sources were not statistically significant. However such differences in the frequency of occurrence of AGRPs among diverse bacterial groups were noted in relation to hospitals. PMID- 3087637 TI - Loss of cytochrome P-450 from hepatic nuclear membranes of rats fed 2 acetylaminofluorene. AB - The cytochrome P-450 content of nuclear membranes isolated from the livers of male Sprague-Dawley rats fed a semipurified diet containing 0.05% w/w 2 acetylaminofluorene (AAF) for 3 weeks, was only about 20% of the values in control rats fed the same diet devoid of AAF. This effect was apparent after only 1 week of AAF treatment and persisted in nuclear membranes from isolated hyperplastic nodules (HPN) generated by 4 cycles of interrupted AAF-feeding. The microsomal cytochrome P-450 content, on the other hand, remained at control levels after 1 week of AAF treatment, and it was only slightly decreased after 3 weeks. In contrast, microsomes from HPN generated by prolonged AAF treatment had markedly decreased amounts of cytochrome P-450. The AAF treatment also caused changes in cholesterol epoxide hydrolase activity, which paralleled those observed for cytochrome P-450 content. Nuclear membranes from livers of rats fed AAF for 3 weeks, and from isolated HPN, had only 30-50% of the cholesterol epoxide hydrolase activity present in controls, whereas the microsomal enzyme activity remained at control levels after 3 weeks of AAF feeding but was 50% depressed in microsomes from HPN. The selective loss of cytochrome P-450 and of cholesterol epoxide hydrolase in hepatic nuclear membrane, but not in microsomes, of rats fed AAF for 3 weeks suggests independent control for these enzymes in these two membrane fractions. Cytochrome P-450 plays a role both in the activation of AAF (N-hydroxylation) as well as in its detoxification (ring hydroxylation) whereas cholesterol epoxide hydrolase initiates the detoxification of cholesterol epoxide. Therefore, our findings suggest the hypothesis that AAF treatment causes an early loss, at the surface of the nucleus, of the last line of defense for detoxification of transforming or promoting metabolites generated by microsomal activation of natural substances such as cholesterol and of xenobiotics such as AAF. PMID- 3087638 TI - Evidence that suramin and aurothiomalate are teratogenic in rat by disturbing yolk sac-mediated embryonic protein nutrition. AB - Suramin (250 mg/kg) and sodium aurothiomalate (100 mg/kg) both induced congenital malformations in the offspring following treatment of pregnant rats at either 8.5 or 9.5 days of gestation. Conceptuses from 9.5-day pregnant rats were cultured for 48 h in homologous serum to which either suramin or sodium aurothiomalate was added for the final 6 h. The presence of suramin up to 5 mg/ml had no effect on the protein content of yolk sacs at harvesting, but at 10 mg/ml caused a significant decrease. In contrast sodium aurothiomalate increased the protein content of yolk sacs at harvesting, in a concentration-dependent manner up to 100 micrograms/ml. Neither suramin nor sodium aurothiomalate significantly affected embryo protein content. When 125I-labelled polyvinylpyrrolidone was added to the culture serum for the final 6 h of culture, radioactivity was found in the yolk sac at harvesting, but not in the embryo. When suramin (2-10 mg/ml) was present for the final 6 h of culture, the quantity of radioactivity measured in the yolk sac at harvesting was significantly decreased in a concentration-dependent manner. No radioactivity was detected in the embryos. Sodium aurothiomalate had no effect on the uptake of 125I-labelled polyvinylpyrrolidone. When rat serum whose proteins were labelled with [3H]leucine was used as culture medium, radioactivity was found in the conceptus (both yolk sac and embryo) at harvesting. Suramin (5 mg/ml), present for the final or penultimate 6 h, significantly decreased the uptake of radioactivity into conceptuses and caused a significant increase in the proportion of the captured radiolabel that was associated with the yolk sac. Sodium aurothiomalate (25 or 500 micrograms/ml) had no effect on the total uptake of radio-label but caused a significant increase in the proportion of total radioactivity captured that was associated with the yolk sac. These data indicate that suramin, by interfering with both the uptake and intralysosomal digestion of protein, and sodium aurothiomalate, by inhibiting digestion of captured protein, disturb the normal pathway of yolk sac-mediated protein utilization with a consequent diminution of the supply of amino acids to the conceptus. The effects of suramin are seen only at high concentration, those of sodium aurothiomalate at much lower concentrations. It is likely that the two drugs exert their teratogenic action by their effects on the yolk sac nutritional pathway with resultant amino acid deprivation of the conceptus at a critical stage of development. PMID- 3087640 TI - Absorption characteristics of macromolecular prodrugs of mitomycin C following intramuscular administration. PMID- 3087639 TI - Modulation by certain factors of metabolic activation of aflatoxin B1 as detected in vitro in a simple fluorimetric assay. AB - Forty compounds belonging to various chemical groups have been tested for their ability to suppress metabolic activation of aflatoxin B1 (AFB1) mediated by rat liver microsome. Microsomal activation has been carried out in an in vitro system containing Tris-buffer at pH 7.2. Production of the reactive metabolite, AFB1 8,9 epoxide, has been measured by separation and detection of its hydrolysis product AFB1 8,9-dihydrodiol as the Tris-diol complex. The complex is separated using simple procedures of biphasic extraction and deproteinization, and detected by its characteristic fluorescence. Quantitation is made by direct comparison of its fluorescence with that of an authentic Tris-diol prepared synthetically. The method is rapid and proved to be highly sensitive and reproducible. A large number of compounds have been observed to modulate at varying degrees the activation of AFB1 in this in vitro system. Many compounds have been tested at several concentration ranges and inhibition curve is constructed in each case from which ID50 values, i.e., the dose needed to bring about 50% inhibition can be obtained. These values expressed as nmol afford a direct and realistic comparison of the inhibitory potential of various modulators. Factors having great inhibitory potential have been identified as retinoids (retinol, retinal, retinoic acid, retinyl acetate), beta-carotene, riboflavin, ascorbic acid, copper, zinc, linoleic acid, p-hydroxy benzoic acid, butylated hydroxyanisole, butylated hydroxytoluene, disulfiram, and phenothiazine. Several other compounds have shown moderate inhibitory potential. The strong inhibition on Tris-diol formation by several vitamins, antioxidants and trace metals shows similarity with their effect on AFB1-DNA adduct formation. It is suggested that these agents may have potential anticarcinogenic activity against AFB1. PMID- 3087641 TI - Oncogenes and human cancer: cause or consequence? PMID- 3087642 TI - Mechanisms of anti-carcinogenesis: the distribution and metabolism of aflatoxin B1 in rainbow trout fed aroclor 1254. AB - Polychlorinated biphenyls (PCBs) have previously been shown to be inhibitors of carcinogenesis in trout. The mechanism of this inhibition was investigated by studying the effects of PCBs on aflatoxin B1 (AFB1) distribution, metabolism and DNA adduct formation, both in vivo and in vitro. A 24 h distribution study of injected tritiated AFB1 showed more radioactivity in blood, liver and bile in fish fed PCBs, but less in residual carcass. The metabolites of AFB1 found in vivo in blood plasma and liver homogenates were shifted by PCB pretreatment towards greater production of the polar metabolite aflatoxin M1 (AFM1) and glucuronide conjugates. The major metabolite in bile of PCB fish was the glucuronide of aflatoxicol M1 (AFL-M1), which was enhanced 15-fold over controls. Levels of aflatoxicol (AFL) glucuronide, the major conjugate in controls, were unaltered by PCBs. The pattern of AFB1 metabolism in isolated hepatocytes from PCB-prefed fish was consistent with in vivo metabolism. AFB1--DNA adduct formation in a 1 h assay was similar in hepatocytes from PCB-fed and control fish. However, the total rate of AFB1 metabolism was significantly elevated in hepatocytes from PCB-fed fish such that the degree of AFB1--DNA adduct formed per unit AFB1 metabolized was 42% lower than control. Similarly, adduct formation in vivo during the first 24 h post-AFB1 injection in PCB fish was not significantly different from controls. However, over a longer 21 day period, adduct levels in PCB fish were only 48-69% of controls (P less than 0.005, analysis of variance), once peak adduct formation was reached. Thus, initial rates of adduct formation may be misleading in the absence of further information on rates of carcinogen metabolism in vitro and/or pharmacokinetics of peak adduct formation in vivo. These results indicate that PCB inhibition of AFB1 carcinogenesis in trout involves dramatic initial changes in carcinogen distribution, metabolism and elimination which, over time, results in a net reduction of DNA adduct formation. PMID- 3087643 TI - Changes in nuclear protein acetylation in u.v.-damaged human cells. AB - We have investigated the levels of nuclear protein acetylation in u.v.-irradiated human fibroblasts. Initially, we measured the levels of acetylation in total acid soluble nuclear proteins and observed two distinct differences between the irradiated and unirradiated (control) cells. Immediately after irradiation, there is a 'wave' of protein hyperacetylation (i.e. a total acetylation level greater than that of unirradiated cells) that lasts for 2-6 h depending on the experimental conditions. This hyperacetylation phase is then followed by a hypoacetylation phase, lasting for many hours, and the total level of acetylation does not return to that of control cells until 24-72 h after u.v. damage. Both the magnitude and duration of each phase is dependent on the dose of u.v. light used. The wave of hyperacetylation is more pronounced at low u.v. doses (i.e. less than 5 J/m2), while the wave of hypoacetylation is more pronounced at higher u.v. doses (greater than or equal to 8 J/m2). Furthermore, the duration of each phase is prolonged when cells are exposed to 2 mM hydroxyurea, an agent which retards the rate of excision repair at u.v.-damaged sites. Examination of the acetylation levels of the individual nuclear proteins indicated that acetylation of the core histones follows the same pattern observed for the total acid-soluble protein fractions. Furthermore, these were the only major proteins in the total acid-soluble fraction observed to undergo the early, rapid hyperacetylation immediately following u.v. damage. Acetylation of histone H1 was negligible in both damaged and control cells, while three prominent non-histone proteins were acetylated only after long labeling times (greater than 4 h) in each case, gradually becoming hyperacetylated in the u.v.-damaged cells. These results raise the possibility that a causal relationship exists between nuclear protein acetylation and nucleotide excision repair of DNA in human cells. PMID- 3087645 TI - Specific inhibitors of the monooxygenase system of Saccharomyces cerevisiae modified the mutagenic effect of 4-nitroquinoline 1-oxide and the deethylation activity of the yeast. AB - A form of cytochrome P-450 is produced in Saccharomyces cerevisiae strain D7 during the logarithmic growth phase in 20% glucose liquid medium. This form was inhibited by metyrapone, tetrahydrofuran and by carbon monoxide, specific inhibitors of cytochrome P-450 in mammals. The inhibition was observed by means of the increase of the genetic activity of 4-nitroquinoline 1-oxide (4-NQO) on logarithmic growth phase cells of D7 strain, adding the inhibitors to the incubation mixture. 4-NQO is a strong direct mutagen on stationary phase cells that is detoxified by the monooxygenase system. The inhibition was measured by determining the decrease of the O-deethylation of 7-ethoxycoumarin in whole cells of yeast depending on different concentrations of inhibitors. A decrease of O deethylation activity was found in the presence of tetrahydrofuran and metyrapone and this behaviour is typical of the cytochrome P-450 species induced by ethanol, as in mammals. Adding sodium phenobarbital to 0.5% glucose liquid medium, a form inhibited only by metyrapone was obtained. The presence of different inducible forms of cytochrome P-450 is evident. PMID- 3087644 TI - Correlation between induction of xenobiotic metabolism and DNA damage from chemical carcinogens in the chick embryo in vivo. AB - Chick embryo liver and lung have high levels of basal mixed-function oxidase (MFO) enzyme activities during embryonic development. These activities are differentially inducible by 3,4,3',4'-tetrachlorobiphenyl (TCB) and phenobarbital (PB) in liver but are not inducible in lung. Nucleated chick embryo erythrocytes have no detectable basal or inducible MFO activities. Following induction by TCB or PB, embryos were exposed to the direct-acting carcinogen methyl methane sulfonate (MMS) or the indirect-acting carcinogens aflatoxin B1 (AFB1) or 7,12 dimethylbenz[a]anthracene (DMBA). DNA damage was measured in liver, lung and blood by the DNA alkaline elution technique. Maximum DNA damage by MMS in liver, lung and blood and by AFB1 and DMBA in liver and lung occurred approximately 3 h after exposure. DNA damage was rapidly repaired in liver and lung, but was not repaired in blood. AFB1 and DMBA caused no detectable DNA damage in blood, even following PB or TCB induction. MMS-induced DNA damage was unaffected by induction in all groups with the exception that PB decreased DNA damage in liver at the low dose of MMS. AFB1- and DMBA-induced DNA damage was increased in liver and decreased in lung following induction by PB and TCB in 14-day embryos. In contrast, AFB1-induced DNA damage was increased by PB and decreased by TCB in 7 day embryonic liver. These results suggest that MFO induction can increase or decrease DNA damage in vivo, but that the direction and magnitude of change in DNA damage can vary depending on the inducer, carcinogen, tissue and the developmental age being investigated. PMID- 3087646 TI - Modification by antioxidants and p,p'-diaminodiphenylmethane of 7,12 dimethylbenz[a]anthracene-induced carcinogenesis of the mammary gland and ear duct in CD rats. AB - The effects of antioxidants on mammary gland carcinogenesis pretreated with 7,12 dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats were examined. The antioxidants used were butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium L-ascorbate, alpha-tocopherol, ethoxyquin and p,p' diaminodiphenylmethane (DDPM), which is an inhibitor of carcinogenesis in the liver, kidney and urinary bladder. Female Sprague-Dawley rats of 50 days old were treated with 2.5 mg/100 g body weight of DMBA, and from 1 week later were given diet supplemented with 1% BHA, 0.7% BHT, 5% sodium L-ascorbate, 1.5% alpha tocopherol, 0.5% ethoxyquin or 0.1% DDPM for 33 weeks and then killed. The incidences of mammary tumors, carcinomas and fibroadenomas in DMBA-treated animals were reduced by diet containing BHA or ethoxyquin. Diet containing BHT or DDPM inhibited the induction of only fibroadenomas. The incidence of ear duct tumors in DMBA-treated animals was reduced by diet containing BHT, alpha tocopherol or ethoxyquin. PMID- 3087647 TI - Progression-linked properties of specific-lesion cell populations from 7,12 dimethylbenz[a]anthracene-exposed rat tracheal implants. AB - The purpose of this study was to determine whether there are any relationships between the morphological expressions of the progression of neoplasia in tracheal epithelium in vivo, and the increased in vitro growth autonomy expressed by carcinogen-altered cell populations isolated from the same tracheas. Rat tracheal implants were exposed for 2 weeks or 4 weeks to 200 micrograms 7,12 dimethylbenz[a]anthracene (DMBA)-beeswax pellets. In the first phase of this study reported earlier (1), the numbers of carcinogen-altered cell populations, identified by their lack of need for exogenous pyruvate and insulin for survival in cell culture, were quantitated 2, 6 and 9 months after the start of the exposures. Before generating the cell cultures, lesions on the pieces of pre exposed tracheal implants were identified by placing them in organ culture for 24 h and collecting the exfoliated cells from the medium for diagnostic cytopathology. Although the pieces of 2-week DMBA-exposed tracheas had not developed any markedly atypical lesions by 9 months, there was a progressive increase in the growth autonomy of the small number of subculturable cell populations (approximately 1/trachea) obtained from this exposure group. This was seen in the decreased time needed in culture to expand the population for testing anchorage-independent growth and tumorigenicity in nude mice. Also, anchorage independent growth was markedly enhanced from 25 to 80% between 2 and 6 months and then to 100% at 9 months. Tumorigenicity did not show an increase. In the 4 week DMBA-exposed group, 74% of the large number of subculturable cell populations (approximately 5.0/trachea) already showed anchorage-independent growth at 2 months. This percentage increased to 94-100% at 6 and 9 months. A progressive increase in tumorigenic cell populations was also clearly seen. At 2 months, 26% of the cell populations inoculated into nude mice formed tumors. This number increased from 45 to 61% at 6 and 9 months, respectively. The pieces of tracheas taken at 2 months after the start of the 4-week DMBA exposure had no markedly atypical lesions. At 6 months one marked atypia was detected, and at 9 months five markedly atypical lesions and two carcinomas in situ were present. The cell populations derived from the explants harboring these lesions showed a high incidence of growth autonomy, e.g. anchorage-independent growth and tumor formation, indicating a close relationship between these properties and the evolving morphological manifestations of tumor development. PMID- 3087648 TI - Inhibition of the prenatal dimethylbenz[a]anthracene-induced tumour initiation in mice by prior administration of 7,8-benzoflavone. AB - 7,8-Benzoflavone (BF) was applied orally via stomach tube in doses of 50, 100, 200 and 400 mg/kg body weight to pregnant NMRI mice on the 18th day of gestation. BF application was followed 1 h later by oral administration of 60 mg/kg body weight dimethylbenz[a]anthracene (DMBA). As a rule this dose of DMBA does not lead to prenatal secondary effects and is not carcinogenic to either the mother animals or the F1 generation. Subsequent promotion of the F1 generation with the tumour promoter 12-O-tetradecanoylphorbol-13-acetate over a period of 12 weeks resulted in a high yield of skin papillomas and lung adenomas when no BF had been applied. With prior application of BF, the tumour yield could be significantly reduced. PMID- 3087649 TI - Relationships between cellular superoxide dismutase and susceptibility to chemically induced cancer in the rat mammary gland. AB - Increasing evidence suggests a role for reactive free radical oxygen species in the multi-stage events of chemical carcinogenesis. We hypothesized that variations in the level of superoxide dismutase (SOD), a major endogenous antioxidant enzyme, may account in part for variations in susceptibility to cancer induced by polycyclic aromatic hydrocarbons (PAH). The SOD activity of mammary epithelial cells from rats with varying susceptibility to dimethylbenz[a]anthracene (DMBA)-induced breast cancer was assayed. Ageing, pregnancy and previous multiple pregnancies reduce susceptibility of Sprague- Dawley female rats to DMBA. These decreases in susceptibility were correlated with increased levels of SOD activity. Only minor differences in SOD activity was observed in mammary epithelium of genetic strains of rats with differences in susceptibility to DMBA. These data suggest that, in models where physiological differences may account for variations in effectiveness of PAH to induce mammary cancer, SOD activity is inversely correlated with breast cancer susceptibility and support the hypothesis that cancer susceptibility may be partially mediated through reactive free radical oxygen intermediates. PMID- 3087650 TI - Intestinal metabolism of nitrosamines. 1. Transport and metabolism of six nitrosamines in isolated perfused rat small intestinal segments. AB - Possible relationships between structure and metabolism of nitrosamines have been investigated in the rat small intestine. Isolated segments of jejunum and ileum were perfused from the luminal side for 2 h with a Tyrode solution containing one of four symmetrical dialkylnitrosamines with 2-5 carbon atoms per side chain, all 14C-labeled at the alpha position, or one of two unsymmetrical nitrosamines, N nitroso-tert-butylmethylamine and N-nitrosomethylbenzylamine, 14C-labeled in the methyl group. Besides measurement of 14CO2 production and covalent binding of 14C to intestinal tissue, the absorbed fluid (absorbate) as well as the perfusion medium and tissue homogenates were analysed by h.p.l.c. for the presence of polar metabolites to assess the intestinal metabolism of nitrosamines. Neither N nitrosodiethylamine nor the two unsymmetrical nitrosamines were metabolized to any significant extent. With increasing chain length of symmetrical dialkylnitrosamines small intestinal metabolism increased dramatically. At a concentration of 1 microM up to 60% and 30% of N-nitrosodipropylamine (NDPA) in jejunal and ileal segments, respectively, and greater than 90% of N nitrosodibutylamine (NDBA) and N-nitrosodipentylamine (NDAA) in both intestinal segments were metabolized during absorption. Metabolites were found also in perfusate and tissue homogenate but generally at lower percentages as compared with the absorbate. With increasing concentrations the percentage of metabolites decreased, the decrease being more pronounced in ileal as compared with jejunal segments. CO2 production and covalent binding were negligible in ileal segments but amounted up to 5-8% and 0.1-0.4% of the dose in jejunal segments perfused with NDPA, NDBA or NDAA. With NDBA and NDAA no concentration-dependent decrease could be observed, the highest amounts of 14CO2 and bound 14C being found at intermediate concentrations. At concentrations below 10 microM metabolic pathways other than alpha-hydroxylation seem to be of greater importance. The toxicological evaluation of the high intestinal first-pass metabolism of NDPA, NDBA and NDAA must await the identification and quantitation of the metabolites formed. PMID- 3087651 TI - Effect of chemical sympathectomy with oxidopamine on systemic blood flow in rats with acute pancreatitis. AB - In response to previous demonstrations that either surgical or chemical sympathectomy can ameliorate the severity of acute experimental pancreatitis, and suggestions that the benefits of sympathectomy are related to alterations in the absolute blood flow or the pattern of blood flow within the pancreas or splanchnic organs, we studied blood flow in rats with acute deoxycholate pancreatitis. The animals had preliminary chemical sympathectomy with a false neurotransmitter (oxidopamine) prior to the experiment and were studied for 120 min after the onset of pancreatitis. All animals with pancreatitis had a fall in cardiac output by 120 min but maintained blood flow to the heart and brain by increasing the percent of cardiac output to these organs. Despite a 61% decrease in cardiac output, at 120 min the chemical sympathectomy group showed an increase in the percentage of flow within the pancreas. However, there was no change in the absolute organ blood flow in any group except at the 10 min measurement, when the pancreata showed an absolute increase in all groups. This study does not support the concept that chemical sympathectomy is beneficial in acute pancreatitis but does indicate a specific and possibly beneficial effect on the distribution of pancreatic blood flow. The decreased cardiac output after chemical sympathectomy is a clear disadvantage of this mode of treatment and probably disqualifies systemic chemical sympathectomy as a treatment consideration. PMID- 3087652 TI - Glycogen synthase and phosphorylase activities during glycogen repletion in endotoxemic rats. AB - The activities of glycogen synthase and glycogen phosphorylase were quantitated in liver and skeletal muscle removed following glucose infusion in hemodynamically stable endotoxin-treated rats. Four hours after the IV injection of endotoxin or saline, rats were infused with 235 mumole/min/kg of glucose or saline for up to 4 additional hr. Saline-infused endotoxemic rats had lower basal glycogen content in muscle and liver, which was associated with an increased phosphorylase a activity in both tissues compared to controls. During the glucose infusion, the rate of glycogen repletion in muscle was similar in the two groups. Skeletal muscle phosphorylase a and glycogen synthase I & D activities were elevated above control values in endotoxemia, while glycogen synthase I activity remain unchanged. These changes in the activity of muscle phosphorylase and synthase are consistent with an increased flux of carbon into and out of glycogen and a normal rate of net glycogen synthesis during glucose infusion in endotoxin treated rats. In contrast to muscle, hepatic glycogen synthesis by endotoxemic animals was reduced compared to glucose-infused controls. Hepatic glycogen repletion in control animals appeared to be mediated primarily by a glucose induced suppression of phosphorylase a activity rather than an increased glycogen synthase activity. Glucose infusion failed to decrease phosphorylase a activity in endotoxin-treated rats, which may be causally related to the impaired ability of these animals to replete liver glycogen. PMID- 3087653 TI - Reperfusion-induced arrhythmias and oxygen-derived free radicals. Studies with "anti-free radical" interventions and a free radical-generating system in the isolated perfused rat heart. AB - We have assessed, whether six agents, that either inhibit free radical formation or scavenge free radicals once they are produced, can reduce the incidence of reperfusion-induced arrhythmias, whether a free radical-generating system (FeCl3 X adenosine diphosphate) can increase the incidence of reperfusion-induced arrhythmias, and whether "anti-free radical" interventions can reduce reperfusion rhythm disturbances caused by the addition of FeCl3 X adenosine diphosphate. With the isolated, perfused rat heart (n = 15 in each group), inclusion of L methionine (1 and 10 mM), superoxide dismutase (2.5 X 10(4) and 1 X 10(5) U/liter), catalase (5 X 10(4), 5 X 10(5), and 1 X 10(6) U/liter), mannitol (50 mM), glutathione (10 microM), or desferrioxamine (150 microM) significantly reduced the incidence of reperfusion-induced ventricular fibrillation and, in many cases, the incidence of reperfusion-induced ventricular tachycardia. The mean duration of sinus rhythm during reperfusion was also increased significantly. Perfusion of hearts with boiled superoxide dismutase (1 X 10(5) U/liter) or boiled catalase (1 X 10(6) U/liter) did not decrease arrhythmias. Conversely, under conditions where, in the control group, the incidence of reperfusion arrhythmias was lowered by increasing perfusate potassium to 6.5 mM, the addition of the free radical-generating system FeCl3 X adenosine diphosphate (0.1 microM X 1 microM) to the perfusion fluid increased dramatically the incidence of reperfusion-induced ventricular fibrillation and tachycardia. Simultaneous perfusion with FeCl3 X adenosine diphosphate and superoxide dismutase (1 X 10(5) U/liter), catalase (1 X 10(6) U/liter), mannitol (50 mM), methionine (10 mM), or desferrioxamine (150 microM) again reduced the incidence of reperfusion-induced arrhythmias and increased the duration of normal sinus rhythm during the reperfusion phase. Thus, addition of six "anti-free radical" interventions reduced the incidence of reperfusion-induced arrhythmias, addition of a free radical-generating system increased the incidence of reperfusion induced arrhythmias, and simultaneous perfusion of the hearts with FeCl3 X adenosine diphosphate and "anti-free radical" interventions again reduced reperfusion rhythm disturbances. These results are further evidence supporting the hypothesis that oxygen-derived free radicals play an important role in the genesis of reperfusion-induced arrhythmias. PMID- 3087655 TI - Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates. AB - To test the hypothesis that atherosclerosis impairs endothelium-dependent vascular relaxation, we examined the effect of the endothelium-dependent vasodilators acetylcholine and thrombin and the endothelium-independent vasodilator nitroglycerin on iliac arteries from normal cynomolgus monkeys and cynomolgus monkeys with diet-induced atherosclerosis. Rings of iliac artery were suspended in organ chambers at their optimal length for generating tension. After preconstriction with prostaglandin F2 alpha, cumulative concentration-response curves to acetylcholine, thrombin, and nitroglycerin were examined. The presence of endothelium was confirmed in each vessel by scanning electron microscopy. Atherosclerotic vessels showed morphologic evidence of moderate to severe atherosclerosis. Acetylcholine produced a maximal relaxation of 65 +/- 10% in the normal group and 27 +/- 10% in atherosclerotic vessels (P less than 0.05). Thrombin (10.0 U/ml) produced relaxation of 39 +/- 9% in the normal group and 13 +/- 7% in atherosclerotic iliac arteries (P less than 0.05). Nitroglycerin relaxed both normal and atherosclerotic blood vessels to an equal extent; maximal relaxation was 92 +/- 4% in normal vessels and 98 +/- 2% in atherosclerotic vessels. To determine if hypercholesterolemia alone produces an abnormality in endothelium-dependent relaxation, we performed two additional studies. First, because veins are exposed to hypercholesterolemia, but do not develop atherosclerosis, we studied relaxation responses to acetylcholine and thrombin in veins from normal monkeys and monkeys with diet-induced atherosclerosis. Veins from normal and atherosclerotic monkeys relaxed to a similar extent upon exposure to the endothelium-dependent vasodilators acetylcholine and thrombin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087654 TI - Dose-related effects of adenosine and bradykinin on microvascular permselectivity to macromolecules in the hamster cheek pouch. AB - The hamster cheek pouch preparation was used to assess microvascular permselectivity responses to three vasodilating agents: bradykinin, adenosine, and papaverine. Fluorescein isothiocyanate-dextran 150 was injected intravenously as a macromolecular tracer. To quantify changes in permeability, we calculated fluorochrome clearance values from the ratio of suffusate to plasma fluorescein isothiocyanate-dextran 150 concentration. The microcirculation was recorded on videotape, using epifluorescence and bright-field light microscopy. Topical application of bradykinin elicited dose-dependent increases in macromolecular permeability. Adenosine also augmented permeability in a dose-dependent fashion. The increases in tracer clearance, relative to control, were 9.4 nl/min for 10( 5) M adenosine and 39.4 nl/min for 10(-4) M adenosine. The standard error for these doses was 1.5 nl/min. Adenosine, 10(-6) M, did not alter permeability. The increment in clearance induced by 10(-4) M was comparable to that of bradykinin, 8 X 10(-7) M. Pretreatment with phenidone had no effect on the permeability response mediated by 10(-5) M adenosine. Topical application of papaverine enhanced the transvascular exchange of macromolecules in one-half of the preparations examined. Comparable doses of adenosine were approximately three times as effective. This study indicated that adenosine, like bradykinin, is capable of modifying microvascular permeability responses in the hamster cheek pouch. This modulatory effect appears to be due to a direct action on the postcapillary microvascular membrane. PMID- 3087656 TI - Oral antihistamine or nasal steroid in hay fever: a double-blind double-dummy comparative study of once daily oral astemizole vs twice daily nasal beclomethasone dipropionate. AB - Seventy-four patients with a well documented history of seasonal allergic rhinitis were randomly allocated to receive either astemizole 10 mg orally per day or beclomethasone 100 micrograms in each nostril twice daily on a double blind double-dummy basis. The patients were studied in a general practice setting and were seen at entry, during the study and at the end of the study by a single observer, the author. Assessment was by diary card incorporating five 10 cm visual analogue scales related to the four symptoms of sneezing, rhinorrhoea, blocked nose and itchy eyes and an overall assessment of hay fever symptoms. Patients were asked if the medication had upset them in any way at each observer assessment. Symptom severity, as recorded by the visual analogue scales, was not significantly different for sneezing, rhinorrhoea, blocked nose or overall between the two groups but the symptom scores for itchy eyes were significantly better for the astemizole group. Adverse effects were minimal and of a minor nature only. There was no real difference between the two groups regarding adverse effects. The study suggests that oral astemizole is at least as good as nasal beclomethasone in the maintenance treatment of hay fever and that it offers the additional advantage of improved control of eye symptoms. PMID- 3087657 TI - An open cross-over trial comparing two doses of astemizole and beclomethasone dipropionate in the treatment of perennial rhinitis. AB - An open cross-over trial comparing astemizole with intra-nasal aqueous beclomethasone dipropionate was carried out in forty-five perennial rhinitis patients attending a S.W. London general practice. Each drug was given for 12 weeks, separated by 4-8 weeks without medication. The principal outcome measure was a 7-day symptom diary completed by patients during weeks 4, 8 and 12. Patients were skin tested to seven common inhalant allergens. Half the patients beginning either regime failed to respond adequately within 2 weeks. Doubling the dose in these patients achieved satisfactory symptom control in an additional 67% on beclomethasone dipropionate and 45% on astemizole. Symptom diary scores showed beclomethasone dipropionate to be significantly more effective than astemizole in the treatment of skin test negative patients; but the two drugs were of equal benefit in the treatment of skin test positive patients. Sneezing and rhinorrhoea were the same on both drugs, but nasal blockage tended to be less severe on beclomethasone dipropionate. There was no significant difference between drugs in the frequency or duration of side effects. Beclomethasone dipropionate and astemizole are equally effective in the symptomatic treatment of atopic perennial rhinitis, but beclomethasone dipropionate may offer superior symptom relief in non-atopic perennial rhinitis. PMID- 3087658 TI - Biochemical markers in the assessment of protein-calorie malnutrition in premature neonates. AB - We studied 135 premature newborns of 26 to 36 weeks gestation, divided into three groups: the control group, 66 premature infants with uncomplicated course; 51 premature neonates with appropriate birth weight for gestational age (AGA), who suffered from clinical problems that delayed oral feeding; and 18 premature infants with small birth weight for gestational age (SGA). When neonates of the same postnatal age were compared, prealbumin concentrations were the lowest in the SGA group at the third and fourth postnatal week. Although the AGA group had the most infants with serious illnesses and the lowest protein-calorie intakes, their prealbumin concentrations did not differ significantly from those of the control group. But when the infants of each group were subdivided on the basis of intakes and weight gain regardless of postnatal age, those with greater intakes showed significantly higher prealbumin values; however, in all groups, the infants with higher intakes were also significantly older. Total proteins and albumin showed similar changes in all groups. Prealbumin concentrations showed great interindividual variability in infants of the same postnatal age. We conclude that prealbumin, albumin, and serum total proteins are not sufficiently sensitive biochemical markers to assess alterations of the nutritional status of premature infants. PMID- 3087659 TI - Simultaneous liquid-chromatographic determination of five antiarrhythmic drugs and their major active metabolites in serum. AB - We report an isocratic "high-performance" liquid chromatographic method for the simultaneous measurement of tocainide, lidocaine, procainamide, quinidine, disopyramide, and their major active metabolites in serum. The drugs are extracted from 200 microL of serum at pH 9.5 with 1.5 mL of 1,2-dichloromethane, concentrated by evaporation, and separated on a CN-bonded-phase column at 40 degrees C (flow rate 2 mL/min) with a pH 7.1 mobile phase of acetonitrile/methanol/phosphate buffer (60/7/33, by vol); the phosphate buffer contains 10 mmol of KH2PO4 and 0.5 mmol of triethylamine per liter. The antiarrhythmic drugs elute in the K' (capacity factor) range of 1.43 (lidocaine) to 5.7 (disopyramide). Results vary linearly with drug concentration to at least 30 mg/L; the detection limit is 0.1-0.2 mg/L. Within-run precision (CV) ranges from 0.9% to 5.0% and day-to-day precision from 2.1% to 6.2%, depending on the specific drug and its concentration in serum. Extraction efficiencies vary from 76% to 85% and analytical recoveries from 98.5% to 103%. At toxic serum concentrations, several basic drugs may interfere with the assay of some antiarrhythmics, but only hydroxyzine, verapamil, and certain local anesthetics interfere at therapeutic concentrations. PMID- 3087661 TI - IgD plasma cell leukemia associated with pyroglobulinemia and pyroglobulinuria. AB - A 70-yr-old man with multiple myeloma IgD developed a plasma cell leukemia producing a serum IgD monoclonal peak and lambda light chains in the urine. When the serum and the urine were heated at 56 degrees C for 30 min both monoclonal bands disappeared. The precipitate failed to redissolve on heating to 100 degrees C. Ion exchange chromatography with a linear gradient of phosphate buffer, pH 8, 0.020-0.300 mol/l and column electrofocusing showed that the serum pyroglobulin was eluted with buffer concentration between 0.040-0.125 mol/l and had an isoelectric point of 5.02, while the pyroglobulin of the urine was eluted with 0.020-0.033 mol/l and had a pI = 7.16. The serum and urine pyroglobulins had a total antigenic community with their correspondent purified proteins. The isolated lambda chains did not change when they were heated at 56 degrees C for 30 min, nevertheless, the heated purified IgD shows some changes in its isoelectric point, molecular mass and antigenicity. These changes in the purified IgD suggest that the pyroprecipitability could be due to conformational features. PMID- 3087660 TI - Use of a quality-control plasma sample to decrease interassay variation in radioimmunoassays of apolipoprotein A-I. AB - The apolipoprotein A-I (apo A-I) radioimmunoassay established in our laboratory involves use of purified apo A-I as the primary standard for quantifying apo A-I in plasma and a pooled plasma (quality-control sample) as a secondary standard to decrease interassay variation. The measured values for apo A-I increased over time as the labeled antigen degraded. We observed these results in two separate studies: (a) apo A-I in plasma from 16 subjects was measured 12 times during four months, and (b) apo A-I in a single pooled plasma was measured 48 times during 10 months. We show that use of a quality-control plasma sample as a secondary standard decreased interassay variation, which was, in part, ascribable to degradation of the labeled antigen. PMID- 3087662 TI - Internalization of exogenous gangliosides in cultured skin fibroblasts for the diagnosis of mucolipidosis IV. AB - The internalization of exogenous mixed brain gangliosides in ML IV cultured skin fibroblasts indicated an impairment of ganglioside catabolism in these cells. Incubation of ML IV, normal and various other lysosomal storage disorders cell lines for five days with exogenous tritium labelled GM3, GD1a or GT1 gangliosides allowed accurate quantitation of the retained gangliosides. This in vitro approach provides a reliable method for the diagnosis of ML IV. PMID- 3087664 TI - Heterogeneity of Morquio disease. AB - Further clinical heterogeneity of Morquio disease, mucopolysaccharidosis IV (MPS IV), is delineated by the observation of a 30-year-old man with unusually mild clinical manifestations. He is 156 cm tall, has comparatively mild skeletal abnormalities and fine corneal deposits. Keratosulfaturia is absent. N Acetylgalactosamine-6-sulfate (GalNAc-6-S) sulfatase (E.C. 3.1.6.-) was markedly reduced in his fibroblasts. The residual enzyme activity exhibited a pH profile comparable to that of patients with the "classical" form of the disorder. From our observation and a review of the literature it is concluded that Morquio disease can be divided in several subgroups: besides the severe ("classical") type A there exist an intermediate and a mild form that are also caused by a GalNAc-6-S sulfatase deficiency. A late-onset variant of Morquio disease, which is due to a deficiency of beta-galactosidase, has been classified as type B. In addition, patients with mild manifestation of the disease and normal activities in fibroblasts of GalNAc-6-S sulfatase and beta-galactosidase have been observed (type C). The genetic nature of the broad clinical variability of Morquio disease is incompletely understood: it is partially caused by different enzyme defects. Other factors thought to influence the clinical expression include the pH profile of the residual enzyme activity and an additional neuraminidase defect. PMID- 3087663 TI - Cardiovascular manifestations in Fabry's disease. A high incidence of mitral valve prolapse in hemizygotes and heterozygotes. AB - Cardiovascular manifestations of Fabry's disease were studied clinically in 10 hemizygous males and 13 heterozygous females. Mitral valve prolapse was found in 5 of 9 hemizygotes and in 5 of 13 heterozygotes examined by echocardiography. Ordinary medical examinations revealed cardiomyopathy in some asymptomatic females, and the diagnosis of the Fabry heterozygote was established by demonstration of specific inclusion bodies in the biopsied myocardium and low alpha-galactosidase activity in leukocytes. Renovascular hypertension of juvenile onset and thromboembolism were also found in 7 patients. It was concluded that Fabry's disease should always be considered in cases of mitral valve prolapse, cardiomyopathy, renovascular hypertension and thrombosis of unknown etiology, and that the Fabry patients should be followed carefully for the early detection of cardiovascular involvements in this disease. PMID- 3087665 TI - Plasma and biliary disposition of pirenzepine in man. AB - The binding of pirenzepine, a selective muscarinic receptor antagonist to plasma and bile, was studied in vitro and in vivo. Plasma and hepatic bile were incubated with 14C-pirenzepine and the bound fraction of 14C-pirenzepine determined by equilibrium dialysis. The bound fractions were 12.6% (s.e.m. = 1.5) and 12.1% (s.e.m. = 1.6) in plasma and bile samples, respectively. After in vitro incubation, the radioactivity in both plasma and bile was removed by exhaustive dialysis against water for up to 94 h, suggesting that the binding was a noncovalent association. 14C-Pirenzepine was also given intravenously to five postoperative patients with T-tube drainage of hepatic bile. In plasma, 12.6% (s.e.m. = 1.8) of 14C-pirenzepine was reversibly bound to albumin. By contrast, in bile 13.4% (s.e.m. = 3.2) was irreversibly bound, mainly to bilirubin glucuronides (greater than 90%). After an intravenous injection of 14C pirenzepine, the radioactivity in plasma decreased bi-exponentially with an initial distribution half-life of 0.24 h and an elimination half-life of 10.2 h. The radioactivity reappeared cyclically in bile, suggesting enterohepatic recirculation of 14C-pirenzepine. PMID- 3087666 TI - Inherited enzyme deficiencies and immunodeficiency: adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies. PMID- 3087667 TI - Immunodeficiency: immunoregulation and immunogenetics. AB - During the past decade, our knowledge of normal immunologic development and function as well as disorders that lead to immunodeficiency has expanded rapidly as a result of the interplay between studies of the immune system in animals and studies of patients with immunodeficiency diseases or with malignancies of the cells of the lymphoid system. The study of immunodeficiency diseases has been particularly valuable in defining the critical stages in the differentiation of stem cells into mature lymphoid effector cells and the roles played by different subpopulations of cells in regulating the immune response. Our understanding of the immunodeficiency diseases has been facilitated by a number of important advances: (a) The identification of distinct surface determinants on lymphoid cells has led to improved procedures for the isolation of defined lymphoid cell subpopulations; (b) the demonstration that both T- and B-cell populations encompass subpopulations of lymphocytes with different and at times opposing functions; (c) the development of in vitro techniques to assess the functional behavior of isolated lymphoid subpopulations; and (d) the isolation and characterization of genes encoding immunoglobulin molecules and the antigen specific T-cell receptor, thus defining at a molecular level the mechanisms leading to antibody diversity and to the organization of a recognition unit on T lymphocytes. These advances have not only been important for our understanding of the pathogenesis of immunodeficiency in patients with congenital and acquired immunodeficiency disorders, but have also provided the scientific basis for more rational approaches to the diagnosis and therapy of these disorders. This report will review (a) the defects in cellular maturation, cellular interaction, and cellular biosynthesis that have been observed in patients with immunodeficiency diseases; (b) the immunoglobulin gene rearrangements that are involved in the generation of antibody diversity; (c) the structure and genetic basis for the generation of antigen-specific T-cell receptors; and (d) potential future applications of molecular genetic approaches to the definition of the pathogenesis and to the treatment of immunodeficiency diseases. PMID- 3087669 TI - The "physiology" of the climacterium. AB - The climacteric represents both a time of declining gonadal function and general aging with subsequent alterations in those organs responsive to sex hormones. Men and women differ in that in women sex hormone production is intimately linked to the presence of gametes. As the number of oocytes is fixed at birth and oocytes are lost at a relatively constant rate, gonadal failure is the inevitable result. When the human life expectancy did not exceed the age of the climacteric, this was not a clinical problem for our species. With our rapidly lengthening life span, however, the medical impact of an extended life span without reproductive hormones becomes significant. In order to address these clinical problems in a humane and cost-effective manner to improve the quality of life for our increasingly aging population, a thorough understanding of the climacteric is mandatory for any physician treating women. Like most concepts in medicine, this one is not new. Borner stated in 1887: The climacteric, or so-called change of life in women, presents, without question, one of the most interesting subjects offered to the physician, and especially to the gynecologist, in the practice of his profession. The phenomena of this period are so varied and changeable, that he must certainly have had a wide experience who has observed and learned to estimate them all....it is desirable in the interest of our patients of the other sex, that the greatest possible light should be thrown upon this question. The modern practitioner will need to apply all the skills and resources available to adequately deal with the multitude of interrelated problems that beset women beyond the climacteric. PMID- 3087668 TI - Peripheral blood mononuclear cells during natural measles virus infection: cell surface phenotypes and evidence for activation. AB - Peripheral blood mononuclear cells from 25 patients with measles and 13 patients with other diseases from Lima, Peru, were studied by immunocytochemical staining for cell surface antigens indicating the type of cell (Leu 4, Leu 3, T8, B1, M1, or esterase) and the state of cell activation (T10 and IL-2 receptor). Measles patients were studied during the first 2 weeks of disease and had no alteration in the proportion of cells which were positive for any subset marker or in the ratio of helper/inducer to cytotoxic/suppressor T cells compared to controls. Measles patients, however, had a greater number of cells expressing the activation antigens T10 and IL-2 receptor than controls. Incorporation of [3H]thymidine was also higher in measles patients when exogenous natural or recombinant IL-2 was added to unstimulated cultured cells. We conclude that the peripheral blood mononuclear leukocytes of patients with measles have normal proportions of helper/inducer and cytotoxic/suppressor T lymphocytes, B lymphocytes, and monocytes but that an increased number of these cells are in an activated state. PMID- 3087670 TI - Spontaneous fractures of uninvolved bones in patients with Paget's disease during unduly prolonged treatment with disodium etidronate (EHDP). AB - Three patients with Paget's disease of bone were treated by disodium etidronate (EHDP) without interruption during periods of 18 to 30 months. In one case the daily dose was also unduly high (approximately equal to 18 mg/kg/day). A moderate to conspicuous diminution of the renal function was observed in all cases. The three patients developed skeletal pain in a gradual but progressively severe pattern. Seven nontraumatic fractures in nonpagetic bones were encountered. EHDP produces blockage of bone mineralization and excessive suppression of bone remodeling, therefore increasing the risks of fracture. EHDP affects not only pagetic bones but normal skeleton. A baseline evaluation of the renal function might help to identify those patients with greater risk to develop skeletal side effects during EHDP treatment. PMID- 3087671 TI - Heterotopic bone formation following total hip arthroplasty in ankylosing spondylitis. AB - Heterotopic ossification is a well-recognized complication of total hip arthroplasty. In a retrospective survey of 98 total hip arthroplasties in ankylosing spondylitis performed between 1970 and 1977, 39.8% showed some evidences of heterotopic ossification. Restriction of hip movements was noted in only two. Heterotopic ossification occurred within one year and was higher (64.6%) in patients with bilateral hip replacements if there was evidence of heterotopic bone formation in one hip. The complications were relatively high in hips with previous operations (55%); trochanteric bursitis (50%); and trochanteric detachment (63.3%). No correlation was found between high erythrocyte sedimentation rate and the incidence or extent of heterotopic bone formation. PMID- 3087672 TI - Indium-111 leukocyte uptake in a case of metastatic tumor. PMID- 3087673 TI - Bronchopulmonary dysplasia in the tiny infant. AB - Bronchopulmonary dysplasia, defined as ventilator or oxygen dependence accompanied by characteristic x-ray changes, occurs frequently in the tiny baby. The authors report their own experience in a large metropolitan hospital. A review of etiologic factors and therapeutic interventions for bronchopulmonary dysplasia in tiny infants is detailed. PMID- 3087674 TI - Hemodynamic variables in infants weighing less than 1000 grams. AB - VVLBW infants pose a challenge in the management of their hemodynamic changes. Data are just accumulating regarding the hemodynamic variables in this very special group. We have described several newly developed methods of monitoring hemodynamic variables in infants less than 1000 gm. In the coming decade, some of these methods may become more refined and routine. PMID- 3087675 TI - Nutrition in very very low birth weight infants. AB - The VVLBW infant's limited nutritional reserves, high requirements for normal growth and development, and gastrointestinal immaturity pose a particularly challenging nutritional problem. Given the potential consequences of inadequate or inappropriate nutritional management, we are obligated to make nutrition a high priority in the overall care of VVLBW infants. PMID- 3087676 TI - The cost of care of the less-than-1000-gram infant. AB - One of the most difficult ethical issues in neonatal intensive care concerns the treatment of extremely low birth weight infants (ELBW). Because of their extreme prematurity, aggressive medical intervention is needed to sustain life. Advances in perinatal medicine have made it possible for these extremely immature infants to survive. More importantly, although the mortality and long-term morbidity are high, particularly for infants less than 700 gm, many of the survivors are expected to become productive members of society and produce measurable economic benefit. The limits set for aggressive management of the VLBW infant have gradually been lowered in virtue of the successful survival at each birth weight. It appears that, with each reduction in the birth weight at which maximal efforts should be used, enough babies have survived to encourage us to continue. As we drive to bring the limit of viability to lower gestations and lower birth weights, we are finding some biologic limitations to extrauterine survival that present technology and knowledge cannot overcome. Unquestionably, there is a need for more comprehensive statistics to allow us to define the lower limit of survival. Because of the poor survival rate among infants weighing less than 700 gm, and because of the high cost of their care and statistically poor quality of life among many of the surviving infants, it has been suggested that perhaps a less aggressive approach should be adopted for those extremely immature infants. However, some recent data indicate that aggressive treatment is effective in saving lives, even at the lower spectrum of birth weight, and many of the survivors are normal or have mild handicaps. The importance of economic considerations to solve the ethical dilemma posed by the intensive care of ELBW infants is being questioned. Concerns that reflect moral absolutes cannot be adequately answered in terms of mere dollars and cents. Although the cost of neonatal intensive care is high on a per diem or per case basis, it appears to be reasonable in relation to the health benefits it provides. For infants in the weight class less than 750 gm, probably none would have survived in the absence of neonatal intensive care. We believe that a policy of benign neglect for the ELBW infant is not justified in the present era of perinatal medicine. Given these considerations, we think that aggressive treatment is reasonable, at least initially at birth.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3087677 TI - Enprostil, in contrast to cimetidine, does not inhibit propranolol metabolism. AB - Enprostil, an orally active prostaglandin E2 analog, is undergoing clinical trials in the treatment of peptic ulcer disease. Because results of animal studies suggested that prostaglandins might affect both hepatic drug metabolizing ability and hepatic blood flow, the effects of enprostil on drug elimination were studied and compared with those of the standard antiulcer drug cimetidine in a double-blind, randomized, crossover study of nine normal subjects. Cimetidine reduced the oral clearance of propranolol by 50%, consistent with the inhibition of drug metabolism reported in previous studies. On the other hand, enprostil had no effect on propranolol elimination. Neither drug altered liver blood flow as assessed either by the clearance of indocyanine green or by the technique of dual route of administration of propranolol. Thus in contrast to cimetidine, enprostil had no effect on hepatic drug metabolism. PMID- 3087678 TI - Transdermal nitroglycerin as a step 3 antihypertensive drug. AB - The antihypertensive effect of transdermal nitroglycerin was tested in 11 men with hypertension (mean age 60 years) whose diastolic blood pressure exceeded 90 mm Hg while receiving a diuretic and a beta-adrenergic blocker. In a double blind, randomized crossover trial the subjects received weekly increments of placebo or nitroglycerin (5, 10, 20, and 30 cm2) for 4 weeks each. The final dose of nitroglycerin was 22.5 cm2 (mean). During week 4 of nitroglycerin dosing, sitting and standing systolic blood pressures were reduced (P less than 0.05). Diastolic blood pressures and heart rates did not change during the study. In the five subjects with systolic hypertension (greater than or equal to 150 mm Hg), the mean reduction in systolic blood pressure was 24 mm Hg (P less than 0.01). Further studies are needed to determine if transdermal nitroglycerin has a role in the treatment of systolic hypertension. PMID- 3087679 TI - Encainide disposition in patients with renal failure. AB - The antiarrhythmic agent encainide undergoes extensive presystemic biotransformation to form O-desmethylencainide (ODE) and 3-methoxy-ODE (MODE) in subjects who exhibit the extensive metabolizer (EM) phenotype for debrisoquin 4 hydroxylation. These metabolites contribute significantly to the overall antiarrhythmic activity and are extensively excreted in the urine. Therefore, the effects of renal impairment on the disposition of encainide and its metabolites were studied in seven EM patients with renal failure and compared with those in eight healthy normal subjects of the same phenotype. After a single dose of encainide, its systemic and oral clearances were significantly lower and its elimination t1/2 was shorter in patients with renal failure than in healthy volunteers. This shortening was explained by a significant reduction in steady state volume of distribution in renal failure. After chronic dosing to steady state, quantitatively similar changes were seen. Chronic oral dosing produced 80% higher levels of ODE (the most pharmacodynamically active metabolite) and 167% higher levels of MODE as compared with healthy volunteers. The prolongations in ECG intervals were similar in the two groups despite the higher encainide dose in the normal subjects. In conclusion, patients with renal failure will require lower doses of encainide because of both reduced encainide clearance and increased accumulation of active metabolites. PMID- 3087680 TI - The effect of aspirin on valproic acid metabolism. AB - Urinary valproic acid (VPA) and VPA metabolite profiles were determined before (day 1) and after (day 2) the administration of antipyretic doses of acetylsalicylic acid (ASA) to seven subjects with steady-state levels of VPA. Of the 13 metabolites assayed by GC/MS, levels of (E)-2-ene VPA and 3-keto VPA were significantly decreased on day 2, whereas those of the VPA conjugates (glucuronide) and 4-ene VPA were significantly increased. The beta-oxidation pathway consisting of (E)-2-ene VPA, 3-OH VPA, and 3-keto VPA was decreased from 24.5% +/- 10.3% of total metabolites excreted on day 1 to 8.3% +/- 4.2% on day 2, a decrease of 66% (P less than 0.05). VPA glucuronide content increased from 50.5% +/- 12.6% on day 1 to 65.5% +/- 14% of total excreted on day 2, an increase of 30% (P less than 0.05). The day 2/day 1 ratios of VPA glucuronide correlated significantly with the day 2/day 1 ratios of VPA mean free fraction (r = 0.9424; P = 0.005) in six of the seven subjects. Inhibition of VPA beta-oxidation by salicylate was sufficient to counterbalance the increased elimination of VPA as its conjugates and explains why total clearance of VPA after salicylate remains unchanged even though the free fraction of VPA is increased. Metabolic profiles indicate that salicylate likely inhibits VPA beta-oxidation by reducing valproyl coenzyme A formation. PMID- 3087681 TI - Giant diverticula of the male urethra: a surprising radiological finding. AB - A case of congenital urethral diverticula in a male is reported. The diverticula were well demonstrated by voiding cysto-urethrography and retrograde urethrography. A review of the relevant literature is given, emphasizing the radiodiagnostic procedures. PMID- 3087682 TI - Selective effects of graft-versus-host reaction on disaccharidase expression by mouse jejunal enterocytes. AB - Graft-versus-host reaction (GvHR) was induced in neonatal mice to produce crypt hyperplasia with and without stunted villi. Lactase activity was measured along individual villi of control and GvHR mice using quantitative cytochemistry. Lactase activity increased in control mice as enterocytes migrated over the lower part of the villus. This increase was followed by a period when lactase activity remained approximately constant. Effects produced by GvHR on this normal profile of development included an extension of the distance on the villus over which enterocytes could continue to increase lactase activity, a reduction in the time needed for an enterocyte to express lactase activity at maximal rate, and an overall decrease in the maximal lactase activity expressed by mature enterocytes. These effects have been quantified by fitting logistic curves to the experimental data. Parallel biochemical analyses of intestinal homogenates showed sucrase, isomaltase, trehalase and maltase activities to increase markedly 7-8 days after the injection of parental spleen cells. Attention is drawn to similarities between these results and steroid induced precocious development of intestinal function in neonatal mice. PMID- 3087683 TI - Lung disease associated with gold therapy. PMID- 3087684 TI - Adverse reactions to five new antidepressants. AB - Postmarketing adverse drug reaction reports for amoxapine, maprotiline hydrochloride, and trazodone hydrochloride and premarketing adverse drug reaction data for bupropion hydrochloride and nomifensine maleate are reviewed, and the role of the new agents in the management of depressive illness is discussed. Nomifensine was withdrawn from markets worldwide because of reports of serious hypersensitivity reactions, especially hemolytic anemia, and marketing of bupropion in the United States was delayed after seizures occurred in bulimic patients in clinical trials. Amoxapine and maprotiline, when taken in overdose attempts, are more toxic and cause more serious central nervous system reactions than the standard tricyclics. Acute renal failure and an increased mortality rate are associated with amoxapine overdose. Amoxapine causes several acute and chronic untoward neurologic and endocrine reactions not commonly associated with the standard tricyclics. For maprotiline and bupropion, maximum doses have been established because of dose-related seizures. Trazodone has minimal effect on cardiac conduction; its main cardiovascular effects are hypotension, orthostasis, and dizziness. The trazodone package insert has been revised to warn of priapism; patients with prolonged or inappropriate penile erections are instructed to discontinue the drug and notify the physician. Serious cardiovascular and neurologic toxicities are rare with trazodone overdose. Of the newly marketed antidepressants, only trazodone offers some advantages over the tricyclic and tetracyclic agents in the areas of side effects and toxicities. The number and type of patients exposed to a new drug during clinical trials is too small for detection of rare but potentially serious adverse effects. PMID- 3087685 TI - A rise in the percentage of large unstained cells in the peripheral blood determined by the Hemalog D90 automated differential counter is a feature of impending myeloid engraftment following bone marrow transplantation. AB - The early phase of bone marrow regeneration has been monitored by automated differential counts on the peripheral blood using a Hemalog D90, following 107 transplant procedures. An elevated percentage of large unstained cells (LUCs) was detected in over 98% of cases and in 72% of cases the rise in percentage LUCs preceded the rise of the total leucocyte count into the detectable range on a Coulter counter (greater than 0.3 X 10(9)/1) by an average of 4 days. These LUCs are shown to be CD8 + T lymphocytes. The ability to detect the earliest signs of regeneration is particularly useful when regeneration is delayed and repeat marrow infusion is considered. PMID- 3087686 TI - T4: T8-lymphocyte ratios in human bone marrow: the effect of sampling technique. AB - Marrow aspirate and trephine biopsy T4 : T8-lymphocyte ratios were compared with peripheral blood values. To do this, a new technique for harvesting marrow cells from trephine biopsies is described. Results show that blood and trephine ratios did not overlap. Marrow aspirate ratios were intermediate suggesting that peripheral blood contamination was causing aspirate T4 : T8 ratios to be falsely elevated. PMID- 3087687 TI - Clinical evaluation of impedance cardiography. AB - We tested the validity of thoracic impedance cardiography for measuring cardiac output in man by comparing absolute values obtained using the non-invasive impedance method with values obtained using the invasive thermodilution method. We also compared per cent changes in cardiac output using impedance cardiography and thermodilution in response to environmental manipulations including cardiac pacing and intravenous administration of ergonovine, dipyridamole, or isoproterenol. Among 19 patients, absolute values for cardiac output, using the impedance and the thermodilution techniques, agreed well (r = 0.85, P less than 0.001). The per cent change in cardiac output by impedance cardiography was positively correlated with the per cent change by thermodilution for the several manipulations (overall r = 0.87, P less than 0.001). Impedance cardiography does appear, in general, to measure cardiac output and stroke volume validly in man, even in situations where heart rate and stroke volume change in opposite directions. PMID- 3087688 TI - Venous plasma adrenaline response to orthostatic syncope during tilting in healthy men. AB - The effect of transient cerebral ischaemia connected with acute orthostatic hypotension on plasma adrenaline and noradrenaline levels was studied in seven healthy male volunteers during tilt. Sublingual administration of 1 mg nitroglycerin was used to block peripheral vascular reflexes and thus to provoke orthostatic intolerance. A consistent increase in plasma adrenaline concentrations (from 19.2 to 104.3 pg/ml on average, P less than 0.01) was found in six subjects who developed clinical signs of collapse after tilting. Plasma adrenaline never changed after tilting without collapse. Posturally stimulated plasma noradrenaline increases were similar yet irrespective of the presence of collapse. PMID- 3087689 TI - The impact of reimbursement changes on doctors' office testing. AB - Most of the recent changes that have revolutionized the way health care is financed include powerful pecuniary incentives to move care out of the hospital and into such outpatient settings as doctors' offices. However, many of these changes also include aggressive utilization reviews with stiff penalties for noncompliance. Thus, although doctors' office testing will continue to expand, this growth may bring more external oversight into doctors' offices. PMID- 3087690 TI - Metabolic bone disease and Paget's disease in the elderly. Part II: Paget's disease. PMID- 3087691 TI - Orthostatic hypotension: clinical spectrum and approach to treatment. PMID- 3087693 TI - The microbiologic etiology of periodontal disease. PMID- 3087692 TI - Comparative kinetics and inhibition of a carbonic anhydrase from Chlamydomonas reinhardii. AB - A native carbonic anhydrase (CA) from Chlamydomonas reinhardii exhibited an apparent molecular weight of 165,000. Denaturation under reducing conditions yielded a single polypeptide, mol. wt 42,000, while the same treatment under nonreducing conditions yielded higher molecular weight aggregates at least two of which could be reactivated to exhibit enzyme activity. In CO2 hydration the enzyme has a Km value of 3.4 mM and a relatively high turnover number. It is very sensitive to inhibition by sulfonamide and moderately sensitive to anion inhibition. In general, the C. reinhardii enzyme resembles many higher plant CAs in its existence as an oligomer. However, it is more like the CAs from animal species in its catalytic versatility and sensitivity to sulfonamides. PMID- 3087694 TI - Phase II randomized comparative clinical trial of Norplant (six capsules) with Norplant-2 (two covered rods) subdermal implants for long-term contraception: report of a 24-month study. National Programme of Research in Human Reproduction. AB - In a randomized clinical study, contraceptive efficacy and bleeding patterns were studied in a group of healthy, regularly menstruating, non-lactating women (n = 84) using two 4.4 cm covered silastic rods containing levonorgestrel, Norplant(R) 2, and compared with another group of women (n = 88) using six 3.4 cm capsules also containing levonorgestrel, Norplant(R). The silastic rods or capsules were placed subdermally in the medial aspect of the upper arm. No method failure was reported up to 24 months of use in this study with either of the device. The bleeding pattern was also similar for both devices as indicated by average episode length, number of bleeding runs and number of spotting days. The continuation rates with both devices were over 80 per 100 users at the end of 12 months and over 65 per 100 users at the end of 24 months. Discontinuations due to expulsion of the device, bleeding problems or personal reasons were few and similar for both devices. The results suggest that silastic-covered rods, Norplant(R)-2, which are comparatively easier to insert and remove and have similar clinical effect, could replace capsules, Norplant(R), as a long-term reversible subdermal contraceptive. PMID- 3087695 TI - Enhanced metabolism of levonorgestrel during phenytoin treatment in a woman with Norplant implants. AB - A 26-year-old woman, treated with phenytoin for 10 years because of epilepsy, had Norplant subdermal implants inserted after a legal abortion. She became pregnant again after nine months of Norplant use. Her plasma levonorgestrel (LNG) levels were followed during one month during phenytoin treatment and then later during one month after discontinuation of phenytoin. During phenytoin treatment, plasma LNG levels were markedly below the levels found in healthy women with Norplant. There was a pronounced, statistically significant increase in plasma LNG levels after discontinuation of phenytoin. The plasma levels of sex hormone binding globulin were markedly above those found in normal healthy women during treatment with phenytoin and decreased significantly after cessation of phenytoin. The effects on the pharmacokinetics of LNG were reflected by effects on the menstrual cycle. During phenytoin treatment, the woman had regular ovulatory menstrual cycles. After cessation of phenytoin, her cycles became irregular and during the study period of one month, no signs of ovulation were found. It is concluded that treatment with phenytoin during use of Norplant subdermal implants enhances the metabolism of LNG to an extent where the contraceptive efficacy is endangered. PMID- 3087697 TI - Bioavailability of levonorgestrel from intravaginal rings in women of low income groups. AB - Two types of intravaginal rings (IVR) containing 50-128 mg of levonorgestrel (LNOG) and 28-60 mg of estradiol were inserted in 18 apparently normal subjects belonging to the low socioeconomic group on day 5 of the cycle. A total of 120 cycles were studied with cyclic insertion and withdrawal. Data on menstrual cycle changes were noted. For bioavailability study, blood samples were collected twice weekly for a period of one month in the first cycle in 8 women. All the plasma samples were analysed for LNOG and progestrone by RIA. Cycle control was excellent in IVR users. Expulsion of the ring was noted in 4 instances. The plasma LNOG levels were found to reach a peak level ranging from 2.7-7.5 ng/ml within 4 days after the IVR insertion. In between day 9 to 24, the plasma levels appeared to be almost steady, and once the ring was removed, the levels dropped off rapidly. The mean plasma LNOG calculated during the steady-state period of the cycle ranged from 1.6-5.1 ng/ml. These mean LNOG levels were found to be inversely correlated with skin-fold at triceps. In all the subjects ovulation was found to be inhibited, as reflected by plasma progesterone values. The range of release rates calculated from plasma steady-state values was 51-119 micrograms/day. The average release rates over the entire period of observation based on area under curve were 102-200 micrograms/day. On the other hand, the release rates obtained from the residual drug in the ring after a period of use ranged from 184-259 micrograms/day. PMID- 3087696 TI - The inhibitory effect of some ionophores on human sperm motility. AB - The inhibitory effect of five ionophores, namely, A23187, nonactin, nigericin, monensin and m-chlorocarbonyl cyanide phenylhydrazone, on human sperm motility were measured with a trans-membrane migration method. The concentrations of A23187 and nigericin that decreased sperm motility to 50% of control were 20 microM (10.5 mg/l) and 8 microM (5.8 mg/l), respectively. Because these two ionophores were more potent than previously reported membrane-active sperm immobilizing agents, we propose that ionophores could be a new category of vaginal contraceptive if a pharmaceutical preparation that is safe to be administered in vivo can be developed. PMID- 3087699 TI - Does nasoenteral feeding afford adequate gastroduodenal stress prophylaxis? AB - Serial pH measurements were performed on 366 gastric aspirates from 20 critically ill patients receiving nasoenteral feeding with Osmolite or Isocal HCN, with no other means of gastric acid buffering. Ten patients (group A) received continuous intraduodenal feeding, and ten patients (group B) received continuous intragastric feeding. Gastric pH was at least 5.0 in 33 (23%) aspirates from group A, compared to 120 (54%) from group B (p less than .001). Only two (20%) group A patients had gastric pH values of 5.0 or greater for at least half of the measurements, compared to six (60%) group B patients. These data indicate that continuous intragastric feeding with Osmolite or Isocal HCN controlled gastric pH better than did intraduodenal feeding. However, neither technique adequately neutralized gastric acidity in these critically ill patients. PMID- 3087698 TI - Gene expression and structure of immunoglobulin epsilon chains. AB - The study of immunoglobulin genes has been an active area of research in recent years. The study of IgE heavy (epsilon) chain gene, in particular, has a significant impact on our understanding of the IgE system. The localization of the epsilon gene in the cluster of mouse heavy chain constant region genes has been determined, and models for gene rearrangements leading to epsilon chain gene expression have been provided. The regulation of IgE antibody production can thus be discussed in the context of these models in combination with knowledge of the cellular basis of IgE production. Comparison of the epsilon chain sequence among human, rat, and mouse has allowed a better understanding of the evolution and structure-function relationship of the epsilon chain. Furthermore, expression of epsilon chain cDNA in Escherichia coli and demonstration of biological activities of expression products have paved the basis for identification of defined peptides representing the structures for recognition by IgE receptors. These studies are discussed in this review. PMID- 3087700 TI - Effects of mannitol on cerebral circulation after transient complete cerebral ischemia in dogs. AB - The effects of hypertonic mannitol on postischemic cerebral circulation were studied in 20 dogs. Mannitol, 2 g/kg iv, was infused into ten dogs during a 2-h period starting 1.5 h after 6 min of complete cerebral ischemia. One hour postischemia, regional cerebral blood flow (rCBF) was 36% in the control group (ten dogs) and 39% in the mannitol group. In the control group, rCBF increased gradually thereafter to 70% of the preischemic value 10 h postischemia, whereas the restoration of rCBF was suppressed in the mannitol group. During the postischemic period, intracranial pressure (ICP) increased significantly in the control group, but it did not change significantly in the mannitol group. The effects of mannitol on rCBF and ICP in the present study can be explained primarily by decreased body water due to urinary loss. The administration of mannitol does not necessarily improve postischemic cerebral circulation. PMID- 3087701 TI - Addition of branched-chain amino acids to parenteral nutrition of stressed critically ill patients. AB - We compared the efficacy of a total parenteral nutrition solution supplemented with 44.6% branched-chain amino acids (BCAA) to standard total parenteral nutrition (19.0% BCAA) in the support of critically ill patients. After a 4-day administration of a randomly assigned solution, amino acids were assayed from femoral venous and arterial samples. The BCAA-supplemented solution caused increases in arterial concentrations of valine, isoleucine, and leucine compared to the control solution. The femoral arteriovenous differences for these BCAA were more positive in patients given the control solution. There were no significant differences in nitrogen balance. Since previous studies showing promotion of nitrogen balance with BCAA did not use a balanced substrate for nonprotein caloric support, the lack of a significant difference in the present study may be due to effective utilization of lipid as a fuel source by both groups. PMID- 3087702 TI - Nitroglycerin-induced intracranial hypertension. PMID- 3087704 TI - APACHE II--a severity of disease classification system. PMID- 3087703 TI - Thioctic acid in Amanita poisoning. PMID- 3087705 TI - Antigen- and lectin-sensitized murine cytolytic T lymphocyte-precursors require both interleukin 2 and endogenously produced immune (gamma) interferon for their growth and differentiation into effector cells. PMID- 3087706 TI - The T-cell receptor recognizes nominal and self antigen independently. A theoretical alternative to the modified self concept. PMID- 3087707 TI - Tissue-type plasminogen activator gene is on chromosome 8. AB - Tissue plasminogen activator is one of the two plasminogen activators, both serine proteases, that catalyze the conversion of inactive plasminogen to plasmin, which then degrades the fibrin network of blood clots. By combining somatic cell genetics, in situ hybridization, and Southern blot hybridization, we localized the human tissue plasminogen activator gene to the pericentromeric region of chromosome 8. PMID- 3087708 TI - Gastric bleeding and/or (?) enteral feeding. PMID- 3087709 TI - Intragastric pH profile during acute respiratory failure in patients with chronic obstructive pulmonary disease. Effect of ranitidine and enteral feeding. AB - The ability of H2 receptor antagonists and continuous enteral alimentation to maintain high intragastric pH in patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation was evaluated by continuously monitoring intragastric pH prior to and following sequential addition of ranitidine or continuous enteral alimentation (or both) to their therapeutic regimen. Prior to therapy, intragastric pH was less than 4.0 for 75 +/- 10 percent of the time, but never less than 1.0. Nevertheless, this moderate gastric acidity was associated with evidence of mucosal injury. Ranitidine failed to continuously maintain a high intragastric pH (pH less than 4.0 for 35 +/- 11 percent of the time; p greater than 0.2 compared to patients treated with placebo). Following administration of continuous enteral alimentation, intragastric pH fell, and ranitidine therapy only partially blocked this increase in gastric acidity induced by continuous enteral alimentation. We conclude that without treatment, patients with COPD who have acute respiratory failure may develop gastric mucosal injury despite the presence of only moderate intragastric acidity; however, ranitidine and continuous enteral alimentation are not effective in maintaining a high intragastric pH. PMID- 3087710 TI - [Antibiotic prophylaxis in orthopedic surgery: considerations on a short experience]. PMID- 3087711 TI - [2 cases of massive bone metaplasia of the Achilles tendon]. PMID- 3087712 TI - [Effect of intrauterine devices on the hormonal profile of the normal menstrual cycle]. PMID- 3087713 TI - [Isolation and typing of Bacillus cereus phages]. PMID- 3087714 TI - Total parenteral nutrition needs in different types of short bowel syndrome. AB - Thirty-nine patients with short bowel syndrome after extensive small bowel resection, with or without associated partial or total colectomy, received continuous total parenteral nutrition followed by discontinuous parenteral nutrition. Home parenteral nutrition was introduced in 16 of these patients; in eight it was permanent. The assessment of nutritional status included body weight; standard urinary and blood studies; albumin, prealbumin, and transferrin serum levels; and both urinary and fecal nitrogen. A statistically significant correlation (P less than 0.001) was observed between the length of the remaining small bowel and the necessary duration of nutritional support. Multivariate analysis allowed us to classify patients into three groups as a function of remaining gut length and the duration of required nutritional support. This study should help to define the best nutritional support protocol for patients with various short bowel syndromes in order to ensure the best possible intestinal adaptation and to improve their quality of life. PMID- 3087717 TI - Let your computer do the talking. PMID- 3087715 TI - The postexercise state: altered effects of insulin on skeletal muscle and their physiologic relevance. PMID- 3087716 TI - Lipid metabolism during exercise: influence of training. PMID- 3087718 TI - Sell your practice--the right way. PMID- 3087719 TI - Beware of hidden contracts. PMID- 3087720 TI - A good impression is worth making. PMID- 3087721 TI - Review the past: refine the present. PMID- 3087722 TI - Insulin secretion and erythrocyte insulin binding in Cape coloured non-obese non insulin-dependent diabetes in the young: effects of sulphonylurea therapy. AB - Studies were performed on 10 Cape coloured non-obese NIDDY (non-insulin-dependent diabetes in the young) patients and 6 controls of similar age, sex and weight. Fasting plasma glucose, glucose assimilation rate, insulin secretion in response to an intravenous glucose tolerance test and percentage binding of radiolabelled 125I-insulin to red blood cells were assessed in all patients before and after one month of glibenclamide treatment. Both insulin secretion (P less than 0.01) and erythrocyte insulin receptor binding (P less than 0.01) were significantly reduced when compared to controls. Although glibenclamide markedly improved the second phase of insulin secretion, the intravenous glucose tolerance test stimulated the total insulin secretion to only 40% of control values. The percentage binding of 125I-insulin to red cell receptors improved considerably with therapy, and did not differ significantly from that of control values. PMID- 3087723 TI - [Interferon secreted by Bacillus subtilis is retained by membranes]. PMID- 3087725 TI - Alfentanil in anaesthesia. PMID- 3087724 TI - Acute renal failure. AB - Acute renal failure (ARF) is common among critically ill patients and renal dysfunction is often associated with the multisystem organ failure syndrome. The mortality of ARF remains high but animal data indicate that prevention and early treatment may decrease the morbidity and mortality. This review defines ARF based on urine volume, laboratory parameters, and clinical presentation. The pathophysiology of prerenal, postrenal, and intrinsic ART are differentiated and diagnostic criteria provided. Preventive therapy, supportive care, and proposed treatments are outlined. Studies examining the prevention and treatment of ARF in animal models and trials in humans are evaluated. Mannitol 0.5-1 g/kg, furosemide 0.5-1 mg/kg initially, and dopamine 1-5 micrograms/kg/min are effective in preventing or decreasing the severity of ARF in animal models. In humans these drugs are effective at maintaining urine output in various clinical situations and converting oliguria to nonoliguria in some patients; however, increased survival has not been adequately proven as of yet. Dialysis and experimental therapy are briefly discussed. PMID- 3087726 TI - [Clinical benefits of new laboratory tests for collagen metabolism]. PMID- 3087728 TI - Frequency of haematuria and proteinuria in relation to prevalence and intensity of Schistosoma haematobium infection in Dar es Salaam, Tanzania. PMID- 3087727 TI - Radiotherapy: adjuvant to management of malignant skull-base tumors. PMID- 3087729 TI - A prospective study of egg excretion in patients with urinary schistosomiasis in Kenya: a preliminary report. PMID- 3087730 TI - [Effect of vitamin A and hormones on the hormonal sensitivity of DMBA-induced mammary tumors in rats]. AB - The treatment of rats with DMBA-induced mammary tumours with vitamin A and hormones in the cyclic regime increases the lifetime of animals, decreases both the tumour growth rate and increases the degree of their differentiation. The treatment with vitamin A alone and in combination with hormones lowers the level of estradiol and progesterone receptors in the rat mammary tumours. The high frequency of receptor-positive tumours and high level of estradiol and progesterone receptors in them were observed under the influence of hormones alone in the cyclic regime. PMID- 3087731 TI - [Surface membrane differentiation antigens of the lymph node lymphocytes in nonspecific lymphoproliferative reactions and lymphogranulomatosis in children]. AB - Monoclonal antibodies ICO and OKT, OKM5, C-ALLA have been used to investigate surface lymphocyte antigens in normal (9), reactive (27) lymph nodes and in lymphogranulomatosis (9) in children. The study has shown that the number of lymphocytes with T and B markers is 45% in normal lymph nodes; OKT4/OKT8 is 0.9. In reactive lymph nodes all lymphocytes have T and B markers; OKT4/OKT8 is, 1.5. T-cell (OKT3+, OKT11+) or B-cell (sIg+, ICO-1+) type differentiation is preferable. B-cell type proliferation with a high number of ICO-1+ lymphocytes appeared in lymph nodes of 4 patients with lymphogranulomatosis. Polyclonal proliferation and differentiation were observed in other 5 children. No correlation between immunology and histologic types of the disease was revealed. PMID- 3087732 TI - [Antiproliferative activity of difluoromethylornithine and the factors decreasing its effectiveness in malignant growth]. AB - The inhibitory effect of difluoromethylornithine (DFMO) synthesized by the authors on the activity of the ornithine decarboxylase (ODC) and proliferation of microbial and mammalian cells in vitro was studied. The in vivo growth of ascite plasmocytoma of solid melanoma B-16 cells in mice was also effectively inhibited by DFMO. But the antiproliferative activity of DFMO in solid tumours was substantially lower. Such a decrease in the antitumour activity may be associated with polyamines released from necrotic areas of solid tumours. As the tumour cells "catch" the vitally important metabolites, their effect inside solid tumours is turned against the tumour cells themselves. The second reason of the decrease in the DFMO activity is adsorption of polyamines on the erythrocyte surface. PMID- 3087733 TI - Ontogeny of nyctohemeral variations of thyrotropin-releasing hormone in rat hypothalamus. AB - The ontogeny of nyctohemeral variations of hypothalamic TRH content was determined in male rats from 7-45 days after birth, exposed to a daily 12-h light, 12-h dark cycle (0600-1800 h light; 1800-0600 h dark) or maintained in complete darkness until 45 days. TRH was extracted from whole hypothalami with 90% methanol and assayed by specific RIA. Hypothalamic TRH extracted from rats at different ages showed immunological, chromatographic, and biological properties identical to those of synthetic TRH. No significant variations in hypothalamic TRH content during the day were observed in 7-, 10-, and 17-day-old rats; a significant change, with a maximal value at 1800 h, was observed in 23-day-old rats, while an adult pattern with a maximal value at 1200 h and a minimal value at 2400 h was found in rats of 31 days of age and became more evident in 45-day old rats. In animals maintained in complete darkness for 45 days after birth, no significant changes in hypothalamic TRH content at 1200 and 2400 h were observed. These findings indicate that environmental cyclic light-dark exposure is required for the development of diurnal changes in hypothalamic TRH content. Furthermore, any study involving hypothalamic TRH determination should take into account the age of animals and the diurnal variations of TRH. PMID- 3087734 TI - Sensitivity of thyrotropin (TSH) secretion to 3,5,3'-triiodothyronine and TSH releasing hormone in rat during starvation. AB - The mechanisms by which plasma T3 and TSH decrease after a 3-day starvation period are not completely understood. In this study we tested the hypothesis of a possible modification in the sensitivity of thyrotroph cell to T3 and/or TRH. For that purpose, TRH tests were performed before and after a 3-day starvation in euthyroid, thyroidectomized, and T3-treated (75 or 175 ng/100 g BW) thyroidectomized male Wistar rats. TRH (10 to 500 ng/100 g BW) was injected iv through a chronically-implanted catheter. In another set of experiments, hypophyseal TSH content was also determined. Our results showed that after a 3 day-starvation plasma TSH decreased in all except hypothyroid rats; TSH responsiveness to TRH was unchanged in euthyroid rats but was increased in hypothyroid rats; and the T3-dependent increase in TSH responsiveness to TRH was significantly amplified. Moreover, there was a significant positive correlation between TSH responsiveness to TRH and hypophyseal TSH content. These results suggest that starvation induces an increased sensitivity of thyrotroph cell to T3. PMID- 3087735 TI - Partial insulin resistance in the mouse BC3H-1 cell line: absent hexose independent actions of insulin. AB - We have studied the regulation of glycogen metabolism by insulin in the insulin sensitive nonfusing muscle cell line BC3H-1. The basal percentage of glycogen synthase I activity was not altered by insulin alone at any concentration, time of exposure, or age of cells tested. The addition of glucose or 2-deoxyglucose to the glucose- and serum-free incubation medium caused a 2-fold increase in glycogen synthase I activity over basal levels, and the effect was enhanced to 3 fold if insulin was added to the medium. Glycogen phosphorylase a activity was not altered by incubation in the presence of insulin, but was lowered by the addition of 2-deoxyglucose. This effect was also enhanced in the presence of insulin. The effect of exogenously added sugar occurred only if a 6 phosphorylatable hexose was used. The effect seen with 2-deoxyglucose was stable to Sephadex G-25 desalting, suggesting that activation of glycogen synthase was the result of a stable (covalent) modification of the enzyme. We were also able to demonstrate the presence of glucose-6-phosphate-activatable glycogen synthase phosphatase activity in the myocytes. The effect of 2-deoxyglucose in the presence or absence of insulin could be completely reversed by including cytochalasin B in the medium, suggesting that both the effect of hexose and the insulin enhancement of its effect were entirely dependent on carrier-mediated hexose uptake. Four insulin-mimetic agents, H2O2 Concanavalin A, Na orthovanadate, and antiinsulin receptor B2 serum, were also tested. Despite different mechanisms of action, each agent qualitatively mimicked insulin in the myocytes. All stimulated hexose transport, glucose incorporation into glycogen, and hexose-dependent activation of glycogen synthase in a manner not additive with insulin, but none increased basal glycogen synthase I activity in the absence of hexose. These results suggest that although insulin is capable of regulating glycogen metabolism both by increasing the uptake of sugar and by altering the activation state of glycogen synthase and phosphorylase, these effects are entirely due to the stimulation of hexose uptake, and hexose independent actions of insulin are absent in BC3H-1 cells. PMID- 3087736 TI - Discordant effects of thyrotropin (TSH)-releasing hormone on pre- and posttranslational regulation of TSH biosynthesis in rat pituitary. AB - To investigate whether TRH regulates TSH production through a pre- or posttranslational mechanism, we determined the pituitary levels of mRNAs for alpha-subunit and TSH beta in male Sprague-Dawley rats given TRH in the presence or absence of thyroid hormones, with or without hypothalamic influence. In normal rats, serum TSH increased 6-fold after a single sc injection of TRH (7 micrograms/kg BW), but the levels of mRNA for both TSH subunits did not differ from the control values. Infusion of TRH, achieved by osmotic minipumps that were implanted sc, increased serum TSH for 3 days. Conversely, the pituitary content of TSH dropped to and remained 35% of that in the controls. In these normal rats, throughout the TRH infusion, the pituitary levels of mRNA for the TSH subunits did not differ from those in the controls. Thyroidectomy increased, by 27 and 75 times, the normal levels of mRNAs for alpha and TSH beta, respectively. TRH, given either as a single injection or a 3-day infusion, did not further elevate these levels. We then studied thyroidectomized animals whose pituitaries were transplanted under their renal capsules. These pituitaries responded to TRH infusion by releasing TSH. T4 injection inhibited this response significantly, but not completely. In spite of this evidence of normal responsiveness to TRH, infusion of TRH for a week did not increase the level of mRNAs for either TSH subunit in transplanted pituitaries. We conclude that in the presence or absence of thyroid hormones, with or without concurrent hypothalamic influence, TRH did not affect rat pituitary level of mRNA for either TSH subunit despite persistent high levels of serum TSH. Therefore, TRH does not regulate TSH production through a pretranslational mechanism. Although a translational regulation cannot be completely excluded, the present data, in conjunction with previous findings, support the hypothesis that TRH regulates TSH production primarily by stimulating both posttranslational carbohydrate processing and secretion of this hormone. PMID- 3087737 TI - Inhibition of prostaglandin synthesis by glucocorticoids in human endothelial cells. AB - The vasodilator prostaglandins (PGs), prostacyclin (PGI2) and PGE2, may contribute to the inflammatory response. Because glucocorticosteroids reduce inflammation, possibly through inhibition of arachidonic acid release, we examined the influence of dexamethasone on PG formation in cultures of human endothelial cells. Binding of [3H]dexamethasone by intact cells was competed by unlabeled steroids and was half-maximal at 1.2 X 10(-8) M. A cytosolic fraction complexed with [3H]dexamethasone and migrated on sucrose density gradient centrifugation with a sedimentation coefficient of 8S. 3H-steroid binding was diminished by unlabeled steroid. Histamine, bradykinin, and the ionophore, A23187, stimulated release of PGI2 and PGE2 to as much as 25 times basal release. Dexamethasone (10(-11) to 10(-7) M) reduced PG formation in cells that were stimulated by histamine, bradykinin, calcium ionophore, or mechanical agitation. The inhibitory effect required at least 4 h to develop, was maximal at 24 h, and persisted after the steroid was removed. Hydrocortisone and triamcinolone had similar effects but were less potent than dexamethasone. Testosterone and progesterone did not affect PG generation. Both arachidonic acid and PGH2 augmented formation of PGs but were not inhibited by dexamethasone. Cortisol-21 mesylate, an antagonist of glucocorticoid receptors, blocked the effects of dexamethasone on PG formation, as did treatment of the cells with cycloheximide. We conclude that glucocorticoids inhibit PG production in endothelial cells by interaction with specific steroid receptors. The steroid-mediated inhibitory effect occurs at the level of arachidonic acid release and depends upon protein synthesis. PMID- 3087738 TI - Low T3 syndrome in cancer patients in relation to weight loss, intravenous hyperalimentation therapy and age. AB - In order to investigate the relation of weight loss and intravenous hyperalimentation therapy to low T3 syndrome, serum T3, T4. rT3 and TBG were determined by radioimmunoassay in 105 cancer patients. The cancer patients were classified into 3 groups, Group I, II and III depending on the grade of weight loss, ranging up to a 5% change in weight loss from a healthy condition, from 5 to 9%, and more than 10%, respectively. Cancer patients under age 59 showed no significant difference in serum T3, T4, rT3 and TBG among these 3 groups. However serum T3 and T3/T4 in cancer patients at age 60 and over were significantly reduced in group III, compared to groups I and II. Serum rT3 values were significantly elevated in group III of elderly cancer patients. The incidence of low T3 syndrome in group III of elderly cancer patients was also significantly higher than in groups I and II. In three out of 5 cancer patients with low T3 syndrome, serum T3 values increased after the intravenous hyperalimentation therapy, whereas no significant change in serum T3 values was observed in two patients who died within one day after the final examination. It is concluded that weight loss produced different effects on peripheral conversion of T4 to T3 between cancer patients under age 59 and over age 60 and glucose plays an important role in the pathogenesis of low T3 syndrome except cases with very poor prognosis. PMID- 3087739 TI - Iodide-induced hypothyroidism in a patient with anorexia nervosa. AB - A 39-year-old woman who had been suffering from anorexia nervosa was found to have hypothyroidism. Serum T4, free T4, T3, free T3 and TSH were 3.19 micrograms/dl, 0.5 ng/dl, 15.3 ng/dl, 1.2 pg/ml and 162.1 microU/ml, respectively. On careful questioning, she was found to have taken an iodine-rich diet. The serum iodine concentration was 122 micrograms/dl (normal: 4-9 micrograms/dl) and urinary iodide excretion was 13.05 mg/day (normal: less than 2 mg). After withdrawal of the iodine-rich diet, her serum T4 gradually increased and TSH returned to the normal range. She was diagnosed as having iodide-induced hypothyroidism. However, no significant elevation of serum T3 or free T3 was observed. Serum T4, free T4, T3, free T3 and TSH were 7.85 micrograms/dl, 0.8 ng/dl, 13.6 ng/dl, 4.3 pg/ml and 6.02 microU/ml, respectively. The iodide perchlorate discharge test result was negative. These findings suggest that there exists some unknown mechanism by which a patient with anorexia nervosa may be sensitive to excess iodide. Furthermore, it is of interest to note that in a recovery phase from the hypothyroid state, normalization of serum T4 rather than T3 is well-correlated to TSH secretion. PMID- 3087740 TI - Effect of irrigation solutions on the filling of lateral root canals. PMID- 3087741 TI - Effects of antiepileptic drugs on pentylenetetrazole-induced epileptiform activity in the in vitro hippocampus. AB - We studied the effects of four antiepileptic drugs on pentylenetetrazole-induced burst discharges in the CA3 region of the in vitro hippocampus. Diazepam and carbamazepine abolished the bursting activity in a gradual and dose-dependent manner. Phenobarbital only decreased the burst frequency. Valproic acid was either ineffective or actually caused an increase in both burst frequency and amplitude. The findings in this model were compared with results obtained by other investigators in a penicillin-induced model of epileptiform activity in the hippocampal slice. Diazepam had a similar effect on both pentylenetetrazole- and penicillin-induced burst discharges, but phenobarbital was ineffective in the pentylenetetrazole model, indicating that these chemically induced hippocampal epileptiform activities may be differentially sensitive to antiepileptic drugs. PMID- 3087743 TI - Pentylenetetrazol-induced convulsion and effect of anticonvulsants in mutant inbred strain El mice. AB - The El mouse is an inbred strain developed from ddY mice and is very susceptible to seizure. In El mice, convulsions could be induced by 18 mg/kg of pentylenetetrazol, which is an inert dose in ddY mice. The features of the convulsions were the same as those induced by the tossing-up procedure, a common method to evoke convulsions in El mice. Phenytoin, phenobarbital, valproate sodium, and ethosuximide clearly inhibited pentylenetetrazol-induced convulsions in El mice. These findings suggest that induction of convulsions by pentylenetetrazol in the El mouse is a simple method as compared with induction of convulsions by the tossing-up procedure, and convulsions evoked by this method are a precise experimental model for the study of hereditary epilepsy and for the evaluation of anticonvulsant drugs. PMID- 3087742 TI - Effects of anticonvulsants on penicillin-induced bursting in guinea pig hippocampal slices. AB - The effects of gamma-aminobutyric acid (GABA) and six anticonvulsants on penicillin-induced bursting were compared in guinea pig hippocampal slices. GABA, phenobarbital, pentobarbital, phenytoin, and diazepam slowed and eventually blocked spontaneous bursts. Low-intensity stimulation at concentrations that blocked spontaneous activity still evoked synchronous all-or-none burst responses, although the threshold increased and the bursts were briefer. Sodium valproate had similar effects, but very high concentrations (approximately 10 mM) were required. Ethosuximide paradoxically increased spontaneous burst rate. This model appears to be differentially susceptible to the actions of GABA and the anticonvulsants commonly used to treat tonic-clonic and partial seizures but not to the antiabsence drugs. PMID- 3087744 TI - Correlates of generalized tonic-clonic seizures with intellectual, neuropsychological, emotional, and social function in patients with epilepsy. AB - Relationships between generalized tonic-clonic seizures and indicators of psychological functioning were evaluated in 94 adults with epilepsy who had exceptionally clear seizure histories. Patients were divided according to lifetime numbers of attacks and the presence or absence of a history of major motor status epilepticus. History of status epilepticus or history of more than 100 individual convulsions was associated with decreased functioning in all areas. Abilities were poorest for the group with a history of status, whereas emotional and psychosocial adjustment were worst in persons having large numbers of single convulsions. Possible reasons for the decreased test scores other than seizures were explored in great detail, but none could account for the differences in performance across the groups. PMID- 3087745 TI - Translocation of nascent secretory proteins across membranes can occur late in translation. AB - Signal recognition particle (SRP) causes an arrest in the translation of nascent secretory proteins in a wheat germ cell-free system. In order to examine at what point during the synthesis of a secretory protein its translocation across the endoplasmic reticulum (ER) membrane can occur, SRP was used to arrest nascent chain elongation at various times during a synchronous translation, thus allowing the generation of nascent chains of increasing length. It was found that SRP can still bring about an arrest as late as when an average of two-thirds of nascent IgG light chain was completed. Rough microsomes were added to translations blocked with SRP to determine if such relatively long nascent chains could still be translocated across the membrane. It was found that nascent chains which had been arrested by SRP, regardless of their length, could be translocated into rough microsomes. In the case of IgG light chain, translocation levels of 50% were still observed with nascent chains corresponding to as much as 70-75% of the intact preprotein. Similar results were observed for the nascent bovine prolactin precursor. These results demonstrate that the synthesis of secretory proteins can be uncoupled from their translocation, and that fairly large nascent chains are capable of crossing the membrane of the ER post-translationally. PMID- 3087746 TI - Schistosoma haematobium treatment with praziquantel: preliminary clinical observations. PMID- 3087747 TI - Radiometric diagnosis of mycobacteria. AB - The aim of this study was to determine the impact of recently developed rapid radiometric techniques on the clinical diagnostic operations of a reference laboratory for mycobacteria. Selective inhibition by rho-nitro-alpha-acetylamino beta-hydroxypropiophenone was used to rapidly screen submitted cultures for identification of mycobacterial species other than Mycobacterium tuberculosis. The radiometric drug susceptibility test was applied only to those cultures presumptively identified as belonging to the Mycobacterium tuberculosis complex. All referred cultures were tested without additional subculture. The results showed that non-pigmented mycobacteria other than Mycobacterium tuberculosis can be screened with about 99% reliability, most of them within 24 hours. Unnecessary drug susceptibility testing of mycobacteria other than tubercle bacilli can be avoided at an early stage, thus shortening the average reporting time of the Mycobacterium tuberculosis complex to nine days following the receipt of the cultures. Ways of limiting erroneous reporting are discussed. PMID- 3087748 TI - Stevens-Johnson syndrome with isolation of Mycoplasma pneumoniae from skin lesions. PMID- 3087749 TI - Unusual clinical features of an epidemic of listeriosis associated with a particular phage type. PMID- 3087750 TI - Differential features of ribosomes and of poly(U)-programmed cell-free systems derived from sulphur-dependent archaebacterial species. AB - The properties of poly(U)-directed cell-free systems developed from the sulphur dependent, thermophilic archaebacteria Desulfurococcus mobilis, Thermoproteus tenax, Sulfolobus solfataricus, Thermococcus celer and Thermoplasma acidophilum have been compared. All systems are truly thermophilic in requiring incubation at temperatures close to the physiological optimum for cell growth. Under optimized conditions the error frequency in tRNA selection is less than 0.4% at 80 degrees C, and synthetic efficiencies (Phe residues polymerized per ribosome in 40 min) span from 4 for Tp. tenax, to 10 for Tc. celer, to 20-25 for D. mobilis and T. acidophilum and to 40 for S. solfataricus. According to requirements for polypeptide synthesis and to degree of stability of the ribosomal subunits' association, sulphur-dependent thermophiles cluster into two groups. Group I organisms (D. mobilis, Tp. tenax, S. solfataricus) harbour 70-S monomers composed of weakly associated subunits, whose poly(Phe)-synthesizing capacity is totally dependent on added spermine while being drastically inhibited by monovalent cations. Group II organisms (Tc. celer and T. acidophilum) contain 70-S particles composed of tightly bonded subunits, whose synthetic capacity is independent of spermine while being totally dependent on monovalent cations. Spermine promotes poly(Phe) synthesis on ribosomes of group I organisms by converting the peptidyltransferase center into an active conformation, while monovalent cations are inhibitory by preventing the interaction between the free ribosomal subunits. The closeness between Tc. celer and T. acidophilum ribosomes provides new insight on the phylogenetic placement of Thermococcaceae. PMID- 3087751 TI - Benzo(a)pyrene hydroxylase activity in human bronchial mucus. AB - Sputum collected from patients with respiratory diseases were examined for presence of benzo(a)pyrene hydroxylase (BPH) activity. The human bronchial mucus used in these studies had significant capability to metabolize benzo(a)pyrene. Clarification of the sputum by agents such as N-acetylcysteine or pancreatin in presence of antibiotics was found to be essential for the detection of BPH activity. In vitro incubation of the clarified human bronchial mucus with benzoflavone caused inhibition, while 7,8-dimethyl-benzanthracene induced BPH enzyme activity. PMID- 3087752 TI - A new algorithm for computing the parameters of linear compartment models in pharmacokinetics. AB - A new algorithm (FADHA) for computing pharmacokinetic parameter estimates has been developed. This technique is based on the simplex method which is used to minimize a nonlinear cost function. An important property of this program is that the convergence is ensured contrary to the well-known linear or nonlinear least squares regression analysis which lead to a lack of convergence or to a false one. Two investigations of the comparative performances of FADHA program and other algorithms were undertaken (hexamethylmelamine and Piracetam pharmacokinetics). Least square analysis of data yielded biased estimates whereas FADHA estimates were unbiased and more precise. This new technique, takes into account all the possible observation errors and uses the concept of a weighting function rather than weights as such. PMID- 3087753 TI - Predictive indices for the identification of high-risk patients. AB - In this article, the predictive indices which have been developed during the last decade to assess the risk of complications during hospitalization are reviewed. These indices are based on the evaluation of nutritional and immunological parameters and are particularly suitable for the identification of the surgical patient at risk for postoperative septic complications. The authors also review the methods which have been proposed for the classification of the severity of disease in critically ill subjects and the sepsis score method for the prediction of clinical outcome in severely septic surgical patients. PMID- 3087754 TI - Abstracts of the 20th annual meeting of the European Society for Clinical Investigation. March 19-22, Scheveningen, The Netherlands. PMID- 3087755 TI - IgE antibody and resistance to infection. II. Effect of IgE suppression on the early and late skin reaction and resistance of rats to Schistosoma mansoni infection. AB - Most helminth parasites induce a strong IgE antibody and elevated eosinophil response in their mammalian hosts and a number of in vitro studies have suggested that IgE, possibly in association with eosinophils, may be an essential element of the host protective immunity against helminth infections. To assess the role of IgE in protective immunity, we examined the effect of suppressing the IgE antibody response on rat immunity to Schistosoma mansoni. Suppression was achieved in neonates by injections of rabbit anti-epsilon chain gamma-globulins, control rats received injections of unspecific gamma-globulins. IgE suppression caused a marked reduction of the inflammatory reaction that developed in the skin of immune rats at the site of a cercarial challenge: the early (30 to 60 min) wheal and flare reaction was abolished, and the late cutaneous reaction (6 to 18 h) associated with intense pruritus, edema and local eosinophilia was greatly reduced. This shows that IgE was critical to the recruitment of effector cells and molecules in the skin during the first 24 h following parasite invasion. Worms were recovered 18 to 30 days after a primary infection and 18 days after a challenge infection from IgE-suppressed and control rats. IgE-suppressed rats cured a first infection as rapidly as the control rats; however, they were two to three times less efficient than the controls at eliminating a second or a third challenge. These observations demonstrate that IgE antibodies are essential for the full development of rat acquired protective immunity against Schistosoma mansoni. PMID- 3087757 TI - Mouse monoclonal antibodies induced by anti-allotype antibody display internal images of the rabbit VHa1 allotype: direct visualization by immunoelectron microscopy. AB - We have previously shown that injection of adult rabbits with anti-immunoglobulin (Ig) antibody (Ab) induces the expression of genetically unexpected Ig markers, i.e., a1 allotypic determinants. We now show that these rabbit Ig markers can also be induced in mice by a similar treatment; in the latter case the a1 determinants are located in the antigen-combining site and thus represent "internal images". Two monoclonal antibodies (mAb) were developed from mice treated with anti-allotype Ab. These mAb were reactive with all homologous and heterologous anti-a1 Ab but not normal Ig; efficiently inhibited the binding of rabbit a1 Ig to anti-a1 Ab; and elicited the production of anti-allotype Ab when injected into normal mice. To determine whether the a1-like determinants on these mAb were located in the antigen-combining site, immunoelectron microscopy was utilized to directly visualize Ab complexes. Complexes composed of intact Ab and anti-a1 Fab fragments yielded uniform binding patterns which were identical to those produced by anti-idiotypic reactions. In each case, an identical tip-to-tip binding configuration was observed with a single Fab fragment attached at an approximate 180 degree angle to the V region terminus of each Ab arm. In contrast, rabbit a1 Ig bound as many as two anti-a1 fragments per Ig arm; these fragments were attached laterally and at right angles to the intact molecule. These mAb thus provide the first direct evidence that Ab2 beta determinants are located in, or near, the antigen-combining site. PMID- 3087756 TI - Analysis of the role of interferon-gamma, interleukin 2 and a third factor distinct from interferon-gamma and interleukin 2 in human B cell proliferation. Evidence that they act at different times after B cell activation. AB - Recombinant interferon-gamma (rIFN-gamma) was able to induce proliferation of human tonsillar B cells activated with suboptimal concentrations of anti-mu antibody. The B cell growth factor (BCGF) activity of rIFN-gamma was not due to substances contaminating the IFN-gamma preparation, nor was it mediated by factors released by T cells or large granular lymphocytes following activation by rIFN-gamma. The response of B cells to rIFN-gamma peaked on day 3 of culture and rapidly declined thereafter, whereas the response of parallel anti-mu-activated B cell cultures to recombinant interleukin 2 (rIL2) appeared on day 3, but continued at least until day 5. In addition, B cells responsive to rIFN-gamma could be at least in part separated from those responsive to rIL2, the former being primarily contained in B cell fractions enriched for high-density small B lymphocytes. Finally, the addition to anti-mu-stimulated B cell cultures of very low concentrations of rIFN-gamma potentiated the B cell proliferation promoted by rIL2. The simultaneous addition of monoclonal antibodies against IFN-gamma and T cell activation antigen to anti-mu-stimulated B cell cultures strongly reduced the B cell proliferative response promoted by three different crude BCGF preparations obtained by polyclonal T cell activation in mixed lymphocyte culture. However, the supernatant from a T cell clone (DP5/11) apparently free of IL2, which manifested a BCGF activity similar to that of rIFN-gamma, still maintained its ability to promote proliferation of anti-mu-activated B cells after complete removal of IFN-gamma. Taken together, our data indicate that although some T cell clones are able to produce a BCGF distinct from both IFN gamma and IL2, these lymphokines account for most of the BCGF activity of supernatants obtained from polyclonal T cell populations. They also suggest that IFN-gamma and the BCGF distinct from IFN-gamma and IL2 act primarily in the earlier phases of B cell activation and potentiate the proliferative response of activated B cells to IL2. PMID- 3087758 TI - Interferon: a cytotoxic T lymphocyte differentiation signal. AB - Human T cell clones which were able to proliferate in response to specific stimuli but could not kill even in the presence of lectins were found to acquire the specific lytic function when interferon alpha or gamma was added on day 1 of the 7-day restimulation culture. These results demonstrate that interferon may act as a cytotoxic T lymphocyte differentiation signal. This signal can be blocked by the monoclonal antibody LeoA1 which recognizes a 70-kDa cell surface structure, involved in cytotoxic T lymphocyte differentiation. PMID- 3087759 TI - A novel approach for preparing anti-T cell receptor constant region antibodies. AB - To obtain antibodies against the individual chains of the T cell receptor (TCR) complex, we have produced chimeric proteins containing domains from immunoglobulin (Ig) and TCR polypeptide chains. Basically, the Ig light chains were used as carriers for the TCR constant (C) region domains. The exons which encode the main body of the C regions of the alpha, beta and the related gamma polypeptide chains were "engineered" into the intronic region between the rearranged Ig variable (V) region and C kappa region genes. All three chimeric genes were expressed in myeloma cells, and the proteins of expected apparent molecular weight were produced. Secreted proteins containing the C beta domain were purified from the culture supernatant by using anti-kappa antibody affinity columns, and two rabbits were then immunized with the purified protein. Both rabbits produced antibodies able to immunoprecipitate the heterodimeric TCR protein. PMID- 3087760 TI - The effect of selective noradrenergic lesions upon the stimulation by noradrenaline of inositol phospholipid breakdown in rat hippocampal miniprisms. AB - The breakdown of inositol phospholipid (PI) stimulated by hippocampal noradrenaline in rat miniprisms in vitro was used as an index of alpha 1 adrenoceptor function after selective noradrenergic denervation. Selective denervation was produced by microinjections of 6-hydroxydopamine (6-OHDA) into either the dorsal noradrenergic bundle (DNAB) or the locus coeruleus (LC), or by systemic treatment with the noradrenergic neurotoxin DSP4 (N-(2-chloroethyl)-N ethyl-2-bromobenzylamine). Fourteen days after these treatments, there was a large depletion of cortical noradrenaline but no change in the stimulation of hippocampal PI breakdown by noradrenaline. It is concluded that selective noradrenergic denervation under the conditions used here does not lead to hippocampal alpha 1-adrenoceptor supersensitivity as assessed by noradrenaline stimulated PI breakdown. PMID- 3087761 TI - Electrophysiological effects of tocainide on canine subendocardial Purkinje fibers surviving infarction. AB - The effects of 10 and 20 mg/l of tocainide on transmembrane action potential characteristics were examined in Purkinje fibers surviving infarction. Infarcted tissue was obtained from canine hearts 24 h after coronary artery ligation. The preparation was stimulated at basic cycle lengths (BCL) of 1000-300 ms. Tocainide reduced the overshoot and amplitude of Purkinje fibers surviving infarction. The maximum upstroke velocity (Vmax) was decreased by tocainide in a dose dependent manner. This effect was more prominent at the shorter BCL. Statistical analysis revealed a significant interaction of the BCL with the drug effect on overshoot, amplitude, Vmax and action potential durations (APD50% and APD90%). Tocainide reduced the effective refractory period (ERP) at the BCL of 1000 ms, but had no significant effect at the BCL of 300 ms. Membrane responsiveness and steady state characteristics of Vmax were shifted significantly to more negative membrane potentials by tocainide. Investigation of the recovery kinetics of Vmax in the presence of tocainide showed an exponential recovery of Vmax with a time constant of 514 ms. These results support the finding that the effect of tocainide on Vmax and conductions is enhanced at faster rates of stimulation. Thus tocainide may be able to depress conduction to produce bidirectional block in the termination of ventricular tachycardia caused by reentry, while having minimal effect on conduction at normal heart rates. PMID- 3087763 TI - Effects of low temperature and calcium on microfilament structure in flagellates of Physarum polycephalum. AB - Microfilament structures of the ridge and the backbone in Physarum flagellates disintegrated selectively within a few minutes upon cooling by ice-water. The elongated cells concurrently rounded up to spherical or irregular and amoeboid shape. When such rounded cells were warmed to 25 degrees C, the microfilament structures were reconstructed within 1 min and cells subsequently returned to an elongated shape. Disruption of microfilaments by cytochalasin A also caused the rounding up of cells, indicating that the rounding up resulted from disintegration of microfilament structures. This transformation induced by the cold treatment was retarded by preincubation of the cells with EGTA for 15 min, but addition of EGTA immediately before the onset of the cold treatment was less effective. The effect of EGTA was cancelled by simultaneous addition of excess Ca2+. Addition of procaine also inhibited the transformation induced by the cold treatment, while caffeine inhibited the recovery of the elongated shape when returned to 25 degrees C. Furthermore, addition of A23187 at 25 degrees C in the presence of Ca2+ mimicked the effect of the cold treatment. Thus, intracellular release of Ca2+ was suggested to be involved in the transformation induced by the cold treatment. Lability of the microfilament structures at a high concentration of Ca2+ was directly proved using Triton-permeabilized cells. Therefore we concluded that low temperature disrupts microfilament structures that are necessary for the maintenance of the elongated cell shape by inducing intracellular Ca2+ release. However, microfilament structures in Physarum amoeba cells were affected neither by the cold treatment nor by high Ca2+ concentration. PMID- 3087762 TI - Early effects of TPA on protein kinase activity in murine thymocytes. Reduction of protein kinase C activity in the cytosol and increase of Ca2+ and phospholipid independent kinase activity in the particulate fractions. AB - Brief treatment of intact thymocytes with TPA and other tumor promoters causes a reduction in protein kinase C activity from the cytosol and an increase in kinase activity in the particulate fraction. In contrast to the activity in the cytosol, which is absolutely dependent on the addition of Ca2+, phosphatidylserine and diolein, the activity in the particulate fraction is independent of these agents. Analysis of target specificity of the particulate kinase activity using exogenous and endogenous substrates suggests that the increased phosphorylation in the particulate fraction is catalysed by protein kinase C with altered catalytic properties. Although interleukin-1 and TPA are both co-mitogens for murine thymocytes, interleukin-1 does not share with TPA its property to alter protein kinase activity in the cytosolic and particulate fractions. PMID- 3087764 TI - Calcium-induced opacification and loss of protein in the organ-cultured bovine lens. AB - A long-term system of organ culture for bovine lenses was used to investigate the effect of osmotic stress on lens opacification and crystallin loss. Lenses were pre-incubated in control medium containing L-[U-14C]tyrosine so that labelled crystallins were produced. The fate of these crystallins was studied in relation to two forms of osmotic stress. The addition of either ouabain or EGTA to the medium induced severe osmotic swelling and disturbance of the lens monovalent cation balance, but only the former treatment was followed by an increase in lens calcium. The changes due to osmotic stress were accompanied by loss of transparency and protein only in the lenses with increased calcium. Both opacification and increased calcium were found largely to be confined to the outer cortical fibres. Protein loss increased with time as lens calcium continued to increase. The protein recovered from the incubation medium was characterized by gel filtration and immunological techniques. The first protein detected was beta L-crystallin, and this formed the major part of the lost protein throughout, although alpha- and gamma-crystallins were detected at a later stage. Increased calcium also resulted in a change in the susceptibility of the crystallins to aggregation, since there was an increase in [14C]tyrosine incorporated into the lens high-molecular-weight (HM) fraction after exposure to ouabain, but not after exposure to EGTA. The relevance of these findings to human cataract is discussed. PMID- 3087765 TI - Echinostoma paraensei: hemocytes of Biomphalaria glabrata as targets of echinostome mediated interference with host snail resistance to Schistosoma mansoni. AB - Earlier in vivo work by Lie et al. (1977) indicated that the innate resistance of the 10R2 strain of Biomphalaria glabrata to PR1 Schistosoma mansoni could be interfered with if the snails were infected previously with another trematode, Echinostoma paraensei. We have studied this interference phenomenon using in vitro methods in an attempt to understand its mechanistic basis. Hemolymph, derived from 10R2 snails infected with E. paraensei for 14-28 days, killed 25% of S. mansoni sporocysts in vitro, significantly less (P less than 0.001) than the 90% killing rate observed with hemolymph from uninfected, control 10R2 snails. Hemolymph from the infected 10R2 snails and from schistosome susceptible M line snails did not differ significantly (P greater than 0.1) in their relative inability to kill S. mansoni sporocysts in vitro. The defect in sporocyst killing exhibited by echinostome infected 10R2 snails was traced to the cellular, rather than the humoral, component of the hemolymph. Preparations containing uninfected 10R2 snail hemolymph and echinostome daughter rediae exhibited significantly less (P less than 0.001) killing of S. mansoni sporocysts than did controls containing only 10R2 hemolymph and S. mansoni sporocysts. Our results suggest that echinostome larvae release factors that interfere with the ability of B. glabrata hemocytes to kill S. mansoni sporocysts. PMID- 3087766 TI - Pupation-temperature range in 12 Drosophila species from different ecological backgrounds. AB - A comparison of pupation-temperature range was made in the laboratory on a temperature gradient (3-38 degrees C) using 12 species of Drosophila representing four species groups and four different ecological backgrounds (temperate-montane forest: virilis group; desert: repleta group; cosmopolitan: melanogaster group; tropical forest: willistoni group). Within groups, differences are found which usually reflect species' distributions. Comparisons of species' mating-, oviposition- and pupation-temperature ranges reveal that pupation most often occurs at temperatures beyond those for mating and oviposition. Each species reflects a different combination of temperature effects. Individual species have different temperature-limits for mating, oviposition and pupation. Temperatures permissive for one response are not predictive of limits on other responses. Among species, temperature can affect a particular response differently. Within groups, species differences can be at high and/or low temperatures for any response, and temperature effects among closely related species can manifest themselves in one, or any combination of responses. One cannot predict which responses will be most and least limited, or at which end of the temperature scale a response will be most limited. Among groups, common, but not absolute temperature ranges generally correspond to the geographic distributions and ecological backgrounds of the species triads. The evaluation of temperature effects on species, based on a single activity, may not be adequate for predicting adaptive strategies. PMID- 3087767 TI - [Effect of synthetic analogs of enkephalins, morphine and their antagonists on the course of experimental traumatic shock]. AB - Effects of naloxone, nalorphine, thyroliberin, morphine and two analogues of enkephalins (FK 33-824 and Tyr-D-Ala-Gly-Phe(NO2)-NH2) on the course of traumatic shock were studied in experiments on rabbits. It was found that antagonists of opioid peptides aggravated the course of traumatic shock and morphine and synthetic analogues of enkephalins exerted positive effects during its treatment. Endogenous opioid peptides are suggested to play the protective role in experimental traumatic shock. PMID- 3087768 TI - [Effect of thyroliberin on respiration in terminal states]. PMID- 3087769 TI - [Antisoporific and cardiotropic properties of new amino acid derivatives of nicotinic acid]. AB - On the models of urethane, nembutal and ethyl alcohol sleep it was shown that nicotinoylcapronate, nicotinoylserine and nicotinoylvaline possess antihypnotic properties being superior to those of cordiamine and on some models phenamine. Nicotinoylvaline and nicotinoylalanine normalized the myocardial contraction in animals with experimental ischemia. PMID- 3087770 TI - [Antibacterial and antifungal agents. VI. Pirfloxacin and related compounds: synthetic and microbiological studies]. AB - A new route to pirfloxacin, a fluorinated pyrrylquinolone with high broad spectrum antibacterial activities, is described starting from 7-amino-1-ethyl-6 fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and 2,5 dimethoxytetrahydrofuran. When the reaction with the latter compound was carried out using the ethyl ester of the above acid the related pyrryl ester formed, which on alkaline hydrolysis gave pirfloxacin. The synthesis and antibacterial activities of the 1-allyl analogue of pirfloxacin and of 7-[2-(1 pyrrolidinomethyl)-1-pyrryl]-1-ethyl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid and its 6-fluoroderivative are also reported. PMID- 3087772 TI - Cell surface involvement in cancer metastasis: an NMR study. AB - NMR spectroscopy is one of the few techniques which has the sensitivity to detect subtle changes to the surface chemistry of cells. It has previously been demonstrated that high resolution 1H NMR methods can distinguish tumour cells with the capacity to metastasis and this information appears to arise from a type of proteolipid in or attached to the plasma membrane. Here we report that the 1H NMR signal, which we have used to identify metastatic cells in rat tumours, is significantly reduced in intensity after cultured cells are treated with trypsin/EDTA. The long T2 relaxation value (greater than 350 ms) observed in metastatic cells is absent after enzyme treatment. 2D scalar correlated NMR (COSY) spectra of these treated cells show that a cross peak normally associated with malignancy and metastatic disease is markedly reduced. These findings indicate that the plasma membrane lipid particle which generates the high resolution spectrum is directly affected by trypsin/EDTA. Alterations to the cell surface properties were also demonstrated in vivo since reduced numbers of metastases were observed in animals injected with enzyme-treated cells. The correlation between the absence of a long T2 relaxation value and the diminished numbers of metastases in animals suggests that the plasma membrane particle is involved in the metastatic PROCESS. PMID- 3087771 TI - Malic enzyme levels are increased by the activation of NADPH-consuming pathways: detoxification processes. AB - The administration to rats of either t-butyl hydroperoxide or phenobarbital, compounds that are metabolized through detoxification processes, produces an increase in specific activity of the NADPH-consuming enzymes, glutathione reductase and NADPH-cytochrome c reductase. These compounds also produce a very significant increase in the specific activity of malic enzyme. Immunoprecipitation with a specific antibody for malic enzyme indicates that specific activity changes are the result of corresponding changes in the amounts of enzyme protein present. The administration of 1,3-bis(chloroethyl(-1 nitrosourea (a glutathione reductase inhibitor) together with t-butyl hydroperoxide abolishes any stimulation of malic enzyme activity. These results indicate that an increase in NADPH consumption induces the synthesis of malic enzyme. Alternatively, a protection of enzyme degradation cannot be rigorously excluded. PMID- 3087773 TI - Phospholipase A2 activity in T-lymphocytes. AB - Phospholipase A2 activity was shown indirectly in T-lymphocytes from rat thymus and a permanent T-cell line by the liberation of arachidonic acid from phospholipids. In addition, phospholipase A2 activity was measured directly with two different substrates, phosphatidylcholine and labelled E. coli. PMID- 3087774 TI - Amino acid sequence analysis of the glycopeptides from human complement component C3. AB - Human complement component C3 has been cleaved completely by trypsin in the presence of 2-propanol. The hydrolysate was fully solubilized and fractionated by reversed-phase HPLC. Two peptides only contained glucosamine, Unambiguous sequence analyses identified Asn-63 of the beta-chain and Asn-268 of the alpha chain as the sites of carbohydrate attachment. A third potential Asn-Xaa-Thr/Ser glycosylation site, Asn-946 of the alpha-chain, is not modified. The different states of glycosylation of the sites cannot be explained by differences in exposure or secondary structure. All three are predicted reverse turn. PMID- 3087775 TI - [Ser7]neurotensin: isolation from guinea pig intestine. AB - Using three antisera to neurotensin of defined regional specificity, a novel neurotensin has been identified in extracts of guinea pig brain and small intestine. The primary structure of the peptide was established as: pGlu Leu Tyr Glu Asn Lys Ser Arg Arg Pro Tyr Ile Leu. Guinea pig neurotensin differs from bovine neurotensin by substitution of a prolyl residue by a seryl residue at position 7. Synthetic [Ser7]neurotensin showed identical chromatographic and immunochemical properties to guinea pig neurotensin. This difference in primary structure may account for some of the anomalous pharmacological effects of bovine neurotensin on guinea pig tissues. PMID- 3087776 TI - Novel enzyme immunoassay for thyrotropin-releasing hormone using N-(4 diazophenyl)maleimide as a coupling agent. AB - A novel enzyme immunoassay (EIA) for thyrotropin-releasing hormone (TRH) was developed which used N-(4-diazophenyl)maleimide (DPM) as a new heterobifunctional agent capable of cross-linking TRH to mercaptosuccinyl bovine serum albumin and to beta-D-galactosidase. The resulting conjugates act as the immunogen producing anti-TRH serum in rabbits and the enzyme marker of TRH in the EIA, respectively. This EIA with a double-antibody technique was sensitive and reproducible in measuring TRH at concentrations as low as 50 pg per tube, and monospecific to the hormone showing no cross-reactivity with the hormone analogue L-pGlu-L-His-L-Pro and TRH constituents. Using this assay, the distribution of immunoreactive TRH in the brain was determined easily in rats. The use of DPM should provide a valuable new method for developing EIA hitherto possible for other peptide hormones containing neither a free carboxy nor a free amino group, using imidazole, phenolic, and indole group(s) of the amino acid as a reaction site. PMID- 3087777 TI - Hydroperoxyfatty acids inactivate the reticulocyte lipoxygenase independently of a hydroperoxidase reaction. AB - From a comparison of 9Ds-HPODE and 13Ls-HPODE and their methyl esters as substrates and inactivating agents of reticulocyte lipoxygenase it is concluded that the compounds inactivate the enzyme independently of any hydroperoxidase reaction. The protective effect of 4-nitrocatechol indicates the formation of Fe(III) complexes of the enzyme with the hydroperoxyfatty acid compounds prior to inactivation. PMID- 3087778 TI - Domain organization of the terminal parts in the fibrinogen molecule. AB - Using limited proteolysis and scanning microcalorimetry it was shown that each terminal part of the fibrinogen molecule is constituted by four co-operative domains. Among these domains two strongly interacting domains are formed by the C terminal part of the beta-chain, while the two other domains are formed by the C terminal part of the gamma-chain. PMID- 3087779 TI - Acid phosphatases bind to the main high density lipoprotein apolipoprotein A-I. AB - The serum protein binding secretory prostatic acid phosphatase (PAP) and lysosomal placental acid phosphatase (LAP) was purified using affinity chromatography on gels containing immobilized acid phosphatases. The protein, which could be eluted from these enzyme affinity gels only with 0.05 mol/l HCl (pH 2.0), was shown to be apolipoprotein A-I (apo A-I), the main structural protein of high density lipoprotein (HDL). PMID- 3087780 TI - Affinity labelling of Escherichia coli ribosomes with a benzylidene derivative of AUGU6 within initiation and pretranslocational complexes. AB - Affinity labelling of E. coli ribosomes with the 2',3'-O-[4-(N-2-chloroethyl)-N methylamino]benzylidene derivative of AUGU6 was studied within the initiation complex (complex I) obtained by using fMet-tRNAMetf and initiation factors and within the pretranslocational complex (complex II) obtained by treatment of complex I with the ternary complex Phe-tRNAPhe.GTP.EF-Tu. Both proteins and rRNA of 30 S as well as 50 S subunits were found to be labelled. Sets of proteins labelled within complexes I and II differ considerably. Within complex II, proteins S13 and L10 were labelled preferentially. On the other hand, within complex I, multiple modification is observed (proteins S4, S12, S13, S14, S15, S18, S19, S20/L26 were found to be alkylated) despite the single fixation of a template in the ribosome by interaction of the AUG codon with fMet-tRNAMetf. PMID- 3087781 TI - Galactosyltransferase-dependent sialylation of complex and endo-N acetylglucosaminidase H-treated core N-glycans in vitro. AB - Purified beta-N-acetylglucosaminide beta(1-4)galactosyltransferase and partially purified beta-galactoside alpha(2-6)-sialyltransferase were used to elongate and terminate glycan chains of agalacto-ovalbumin and endo-beta-N acetylglucosaminidase H-treated yeast invertase in vitro. In the presence of both transferases, 0.1 mol sialic acid was incorporated per mol agalacto-ovalbumin within 24 h. Evidence is presented to show that purification of the galactosylated intermediate increases the efficiency of sialylation. Incorporation of sialic acid into endo-beta-N-acetylglucosaminidase H-treated oligomannose glycoproteins may be useful for in vivo stabilization of these glycoproteins by preventing uptake in liver or reticuloendothelial cells. PMID- 3087782 TI - Use of quin 2 to measure calcium concentrations in ovine anterior pituitary cells and the effects of quin 2 on secretion of growth hormone and prolactin. AB - Intracellular free Ca2+ concentrations [Ca2+]i were measured in ovine anterior pituitary cells using the quin 2 technique. Thyrotropin-releasing hormone (TRH) increased, dopamine decreased and growth hormone-releasing hormone (GHRH) had no detectable effect on [Ca2+]i. Loading the cells with quin 2, at an intracellular concentration less than that used during calcium determination, reduced both basal growth hormone (GH) and (to a small extent) prolactin secretion. Loading cells with quin 2 also markedly reduced GHRH-stimulated GH secretion. However, TRH-stimulated prolactin secretion was 3-times basal irrespective of quin 2 loading. The results indicate that the use of quin 2 to measure [Ca2+]i in some cell types may be complicated by actions of quin 2 on cellular function. PMID- 3087783 TI - Pertussis toxin alters the growth characteristics of Swiss 3T3 cells. AB - Pertussis toxin (islet-activating protein) treatment of intact Swiss 3T3 cells causes a time- and dose-dependent loss of availability of a 40 kDa membrane protein for toxin-catalyzed ADP-ribosylation in subsequent incubations with [32P]NAD. In parallel, [3H]thymidine uptake by quiescent cells stimulated with fresh serum, cell doubling time and cell saturation density are all decreased 30 50%. These results cannot be accounted for by the potential effect of the toxin on cell cAMP levels. They suggest that a pertussis toxin substrate, probably Gi, modulates some component of growth regulation in Swiss 3T3 cells. PMID- 3087784 TI - Kinetics of sulfation in the rat in vivo and in the perfused rat liver. AB - Sulfation of phenols and similar low-molecular-weight substrates in the rat in vivo is a rather complex process. Besides enzyme kinetic parameters, cosubstrate availability (indirectly measured by serum sulfate concentration) and competition with glucuronidation also play a role. For some substrates extensive extrahepatic sulfation occurs, accounting for more than 50% of the total-body sulfation capacity. However, the hepatic contribution may be under-estimated when drugs are administered into the hepatic portal vein, because saturation of hepatic metabolism may occur under those conditions. Inside the liver, sulfation is located primarily in zone 1, the periportal area. This can be shown in the single pass perfused rat liver by perfusion in either the normal or retrograde flow direction. In the rat sulfate conjugates are eliminated preferentially in urine, whereas glucuronides are excreted to a high extent in bile. Therefore, it is important to collect both bile and urine in the characterization of pharmacokinetics of conjugation in vivo. Selective inhibition of sulfation by pentachlorophenol and 2,6-dichloro-4-nitrophenol facilitates studies of the role of sulfation in elimination of its substrates, and the competition between sulfation and glucuronidation for the same substrate. PMID- 3087785 TI - Comparison of the efficacy of subcutaneous and nasal spray buserelin treatment in suppression of testicular steroidogenesis in men with prostate cancer. AB - The comparative efficacy of subcutaneous injections and intranasal spray in the maintenance of suppression of testicular function in men with advanced prostatic cancer treated with a gonadotropin-releasing hormone (GnRH) agonist, Buserelin, was evaluated in a nonrandomized clinical trial. After a common induction period of 1 week's treatment with 500 micrograms three times daily by subcutaneous injection, patients were allocated into one of two groups for maintenance therapy with either subcutaneous (200 micrograms once daily) or intranasal (400 micrograms nasal spray three times daily) Buserelin therapy. Plasma luteinizing hormone (LH) and sex steroid (testosterone [T], dihydrotestosterone [DHT], and estradiol [E2]) patterns were studied before the start and at days 1, 7, and 14 and months 2, 4, 6, and 12 on maintenance regimens. During the maintenance therapy, age-adjusted T levels were markedly suppressed to near-castrate levels in both treatment groups. Despite this marked suppression, age-adjusted T levels were consistently lower in men treated with the subcutaneous regimen from the 2nd week to the 12th month of treatment in morning pooled specimens as well as in detailed sampling over a 24-hour period after 12 months of continuous treatment. A similar pattern of enhanced suppression by the subcutaneous regimen was also observed for age-adjusted DHT, but not E2, levels during the study. Neither the magnitude nor the time course of T suppression by GnRH analog treatment could be entirely explained by the nature of the decline in plasma LH levels, which fell much less and more gradually over a 12-month period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087786 TI - Pulsed CO2 laser versus conventional microsurgical anastomosis of the rat uterine horn. AB - The effect of pulsed CO2 laser treatment on tissue reaction and fertility was evaluated. The left uterine horn was cut with a pulsed CO2 laser in 16 rats. In eight other rats, the left uterine horn was cut with microscissors. The anastomosis in both groups was accomplished by microsurgical techniques. The adhesions were mostly filmy after laser treatment, as compared with thick adhesions in the conventional group. Absence of adhesions was found in 62.5% and 50% of the laser and conventional surgery group, respectively. Histologically, some degree of fibrosis in the muscularis layer of the uterine horn was seen in the conventional group, whereas proper muscle continuity was seen in the laser treated group. The pregnancy rates were 81% and 87.5% in the laser and conventional groups, respectively. PMID- 3087787 TI - Stimulation of multiple follicular growth for in vitro fertilization by administration of pulsatile luteinizing hormone-releasing hormone during the midfollicular phase. AB - Pulsatile subcutaneous administration of LH-RH (14.4 micrograms/pulse/90 minutes) during the midfollicular phase (days 7 to 11) of the cycle induced significant increases in circulating LH, FSH, and E2 in all eight women treated. When CC (150 mg/day on days 2 to 6) was administered prior to the LH-RH, multiple follicular development occurred, five to seven mature follicles (greater than 16 mm) being found on day 12 of the cycle. The administration of pulsatile LH-RH in this manner may prove to be an additional regimen for use in IVF programs. PMID- 3087788 TI - Regulation of human prolactin secretion by gonadotropin-releasing hormone in vitro. AB - The regulation of human prolactin (PRL) secretion by gonadotropin-releasing hormone (GnRH) was evaluated with human pituitary monolayer cell cultures. Synthetic GnRH stimulated PRL secretion when exposed to cells in an estrogen depleted environment. This response was inhibited by pretreatment of the cells with 17 beta-estradiol (E2). A 10(-5) M GnRH antagonist inhibited luteinizing hormone (LH) but not PRL secretion when cells were maintained in an estrogen depleted environment. However, the GnRH antagonist inhibited basal PRL secretion when cells were maintained in medium containing 10(-8) M E2. The 10(-5) M GnRH antagonist, when coincubated with 10(-5) M GnRH inhibited the release of PRL in an estrogen-depleted environment. However, coincubation of the 10(-5) M GnRH antagonist with 10(-5) M thyrotropin-releasing hormone (TRH) failed to inhibit PRL secretion. Incubation of 10(-8) M TRH and 10(-8) M GnRH produced a synergistic release of PRL in an estrogen-depleted environment. These observations led us to conclude that GnRH stimulates PRL secretion by direct action on human pituitary cells and that GnRH acts either via the gonadotrope or through receptors on the galactotrope other than that acted upon by TRH to release PRL. PMID- 3087789 TI - Correlation of serum estradiol levels and ultrasound monitoring to assess follicular maturation. AB - Thirty-eight patients underwent 38 cycles of induction of ovulation using stepwise human menopausal gonadotropin and human chorionic gonadotropin (hCG) administration. Ultrasonography was performed on the day of hCG injection. The mean age +/- standard error of the mean (SEM) of the patients was 32.9 +/- 0.8 years, and the duration of infertility ranged from 1 to 14 years (median, 2.8). Ultrasonographic measurements were obtained of the largest diameter and the volume of the dominant follicles as well as all other follicles in both ovaries. Data were analyzed by Student's t-test, regression analysis, and analysis of variance. The mean +/- SEM diameter of dominant follicles was 1.8 +/- 0.1 cm, and the volume of dominant follicles was 3.5 +/- 0.8 cm. The mean +/- SEM serum estradiol (E2) level before hCG administration was 659 +/- 62 pg/ml. Significant correlations were found between preovulatory serum E2 levels and the total follicular volume of both ovaries (r = 0.41, P less than 0.05) and follicular volume of the ovary containing the dominant follicle (r = 0.42, P less than 0.01). No significant correlation was observed between the diameter of the dominant follicle and serum E2 levels. These results suggest that ultrasound findings reflect growth, whereas serum E2 levels primarily detect functional activity of follicles. PMID- 3087790 TI - Induction of ovulation with pulsatile subcutaneous administration of human menopausal gonadotropin in anovulatory infertile women. AB - Pulsatile administration of human menopausal gonadotropin (hMG) via the subcutaneous route was evaluated in 15 patients with various ovulatory disorders. Administration of hMG was started at a dose of 4.6875 IU (75 IU/day) or 9.375 IU (150 IU/day) per pulse every 90 minutes. Ovulation was observed in 26 (92.9%) of 28 treatment cycles, and two singleton pregnancies were confirmed. Ovarian hyperstimulation was observed in 1 to 26 ovulatory cycles; however, no other side effects were observed during treatment. A regimen of 75 IU/day resulted in a significant increase (P less than 0.0001) of the total dose and prolongation of the treatment period for induction of ovulation, as compared with that of 150 IU/day. Shortened luteal phases occurred in ovulatory cycles induced by pulsatile subcutaneous treatment. Human chorionic gonadotropin administration given every other day until the midluteal phase significantly prolonged the duration of the luteal phase (P less than 0.05). This treatment in patients with the polycystic ovary syndrome was followed by a normalization of luteinizing hormone/follicle stimulating hormone ratio and resulted in a successful induction of ovulation in 8 to 10 cycles. The present data demonstrated that pulsatile subcutaneous administration of hMG was effective in inducing follicular maturation and ovulation in patients with various types of anovulatory infertility. PMID- 3087791 TI - The association between preovulatory serum 17 beta-estradiol pattern and conception in human menopausal gonadotropin-human chorionic gonadotropin stimulation. AB - One hundred forty-four women suffering from obstructive tubal disease underwent laparoscopy for in vitro fertilization and embryo transfer (IVF-ET). Ovulation was induced by a human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) protocol. The patients were divided according to their estradiol (E2) response to hMG/hCG administration: group A, an increase of E2 levels on the day after hCG administration (day +1); group B, a decrease of E2 levels on the day after hCG administration. Each of these groups was further subdivided into high responders (E2 greater than 500 pg/ml on day 0), designated A-1 and B-1, respectively, and low responders (E2 less than 500 pg/ml on day 0), designated A 2 and B-2, respectively. Patients responding in an A-1 pattern had significantly higher E2 levels from day 0 to day +8. Fertilization and cleavage rates did not differ among the groups, nor did luteal-phase progesterone. Twenty-one pregnancies were achieved from 126 transfers (17%), of which 16 (75%) occurred in women responding in an A pattern. We recommend that laparoscopy be deferred in women responding with a B pattern, because this preselection may increase pregnancy rates per IVF-ET cycle. PMID- 3087792 TI - The use of strontium-substituted media for capacitating human spermatozoa: an improved sperm preparation method for the zona-free hamster egg penetration test. AB - An improved procedure for human sperm capacitation based upon calcium deprivation using a modified Tyrode's medium is described. Replacement of CaCl2 by SrCl2 significantly increased the penetration of zona-free hamster eggs after 20 hours of sperm preincubation, compared with parallel sperm aliquots incubated in normal medium. The effect of an extra 4 hours' sperm preincubation produced no significant shift in fertilizing ability. Addition of 0.1 mM ethyleneglycol-bis (beta-amino-ethyl ether)-N,N,N',N'- tetraacetic acid (EGTA) to the strontium substituted medium resulted in a further significant increase in the penetration rate as well as a significant increase in polyspermy. The average increase in the penetration capacity (penetration rate X polyspermy) of the strontium/EGTA preincubated spermatozoa was approximately tenfold, with no significant shift as a result of an extra 4 hours' preincubation. PMID- 3087794 TI - [Effect of cerebral hypoxia and hyperventilation hypocapnia on the epileptiform activity of the cerebral cortex of the cat]. AB - Influence of cerebral hypoxia and hyperventilatory hypocapnia on the ECoG and focal epileptiform activity of the cerebral cortex induced with local application of strychnine was studied in cats with transection of spinal cord at C1. Although both hypoxia and hypocapnia produced synchronization of the cerebral cortex electrical activity, i.e. exerted the same effects on the ECoG, their influence on cortical excitability was quite different: hypoxia suppressed the epileptiform activity whereas hypocapnia facilitated it. PMID- 3087793 TI - [Adsorption of gastric juice pepsin by activated charcoal]. PMID- 3087795 TI - [Suppressive effect of carbon dioxide on excitation of the cold receptors of the nasal cavity of the cat]. AB - The impulse activity of afferent fibers was studied in n. ethmoidalis. While the room air was being sucked in through the nasal cavity to choanes, marked excitation of cold receptors of the nasal cavity walls occurred. In the air current from the choanes to the nostrils, the activity of the receptors was depressed. Insufflation through the nasal cavity of the mixtures of CO2 (1, 3, 6%) with air also depressed the activity of cold receptors. The degree of the depression depended on the concentration of CO2. The cold receptors of nasal cavity like the lung stretch receptors, have the features of chemoreceptors. Their activity is depressed with physiological concentrations of CO2 in the air. PMID- 3087796 TI - Induction of DNA single-strand breaks and DNA synthesis inhibition by patulin, ochratoxin A, citrinin, and aflatoxin B1 in cell lines CHO and AWRF. AB - Four mycotoxins, patulin, ochratoxin A, citrinin, and aflatoxin B1 (AFB1), were compared for their cytotoxicity, DNA synthesis inhibition and DNA damage in CHO and AWRF cells. The concentrations causing a 50% inhibition of colony formation in CHO cells were 0.07, 33, 31, and 10 micrograms/ml, respectively, for patulin, ochratoxin A, citrinin, and AFB1. Values obtained for AWRF cells were 0.011, 6.4, 6.7, and 0.15 micrograms/ml, respectively. Patulin strongly inhibited DNA synthesis in both CHO and AWRF cells, at concentrations over 4 micrograms/ml. Ochratoxin A and citrinin elicited mild inhibition of DNA synthesis (up to 20%) at concentrations greater than 50 micrograms/ml. AFB1 at concentrations over 5 micrograms/ml strongly inhibited DNA synthesis in AWRF cells but stimulated DNA synthesis in CHO cells. In accordance with these findings, AFB1 induced single strand breaks in the DNA of AWRF cells only. Patulin induced about the same levels of DNA breaks in both types of cells, at concentrations greater than 2 micrograms/ml. Citrinin and ochratoxin A produced DNA breaks in CHO cells, at a very high concentration of 200 micrograms/ml. The number of breaks induced in AWRF cells was not statistically significant. The results suggest that the different effects of AFB1 on CHO and AWRF cells are due to the different ability of these cells to metabolize AFB1 to the ultimate carcinogen AFB1-8,9-oxide by microsomal cytochrome P-450-dependent oxygenases. The effects of the other mycotoxins not requiring the metabolic activation were comparable for both cell types. PMID- 3087797 TI - T-cell subsets in the murine thymus during chemically induced leukemogenesis. AB - T cell leukemias were induced in BDF 1 mice by methylnitrosourea (MNU). The phenotype of the leukemic cells is Thy1.2 +, PNA-, TdT+, TL+ and heterogeneous with respect to Lyt-1 and Lyt-2. About 70% of the leukemias have elevated amounts of gp70. During latency period of at least 9 + 12 weeks an early reduction in the various thymic cells and the CFU-S is observed, with almost complete recovery. Later PNA+ cells are reduced. Hydrocortisone treatment delays or enhances leukemogenesis, dependent on the time interval between hydrocortisone and MNU. Some mice show elevated amounts of gp70 in their bone marrow 2--3 weeks after MNU. The problem of target cells in the bone marrow and the thymus is discussed. PMID- 3087798 TI - Influence of 0.02 M EDTA and 3 M KCl on surface of Hymenolepis diminuta and composition of isolated proteins. AB - The glycocalyx of Hymenolepis diminuta (Cestoda, Cyclophyllidea) was isolated using 0.02 M EDTA or 3 M KCl. It was shown in the electron micrographs that 0.02 M EDTA did not damage the tapeworm plasma membrane, eliminating glycocylax only, in contrast to 3 M KCl which disrupted tegument up to the basal membrane. The protein analysis of extracts and the supernatant of homogenate of the whole tapeworm strobila by polyacrylamide gel electrophoresis (PAGE) and dodecyl sulphate-polyacrylamide gel electrophoresis (SDS) electrophoresis revealed that the substance extracted with 3 M KCl was more abundant in protein fractions than the two remaining ones. The substance extracted with 0.02 EDTA, collecting the tapeworm glycocalyx possessed the smallest amount of protein fractions, however, some of them were more abundant. PMID- 3087799 TI - [Arndt-Gottron scleromyxedema without paraproteinemia]. PMID- 3087800 TI - [Quantitative determination of phenoloxidase (EC 1.14.18.1). Absorption behavior of mushroom and potato tyrosinase]. PMID- 3087801 TI - A double-blind comparison of terfenadine and mequitazine in the symptomatic treatment of acute pollinosis. AB - This study was a double-blind, parallel group comparison of terfenadine (TRF) 60 mg b.i.d. and mequitazine (MQZ) 5 mg b.i.d. for 7 days in the symptomatic treatment of acute pollinosis. The trial took place in the same geographic area and during the same pollen season (May-July 85), to ensure homogeneity of the study population. The fourteen investigators participating in this multicentre trial recruited 141 patients (69 TRF; 72 MQZ) suffering from well-documented pollinosis, mainly hay fever and sometimes allergy to tree pollens. Symptoms (nasal itching, sneezing, rhinorrhoea, obstruction, conjunctivitis) and possible somnolence were rated daily using a 4-point rating-scale of 0 to 3 by the patient on a diary card. Assessment of over-all efficacy and tolerability - focusing on atropinic side-effects - was made at the end of the seven-days treatment period by the physician, after reviewing the diary card and questioning the patient. The means score profile of each symptom for the study period was similar with the two treatments. Both had a fast onset of action with the regression of the total symptoms' score being already significant at day 1. Over-all assessment of efficacy at day 7 showed no significant difference between the two treatments. The daily somnolence scores however showed a clear and significant difference between the two drugs: the frequency of moderate to marked somnolence from day 2 to 7 was around 15% with MQZ and around 5% on days 2 to 5 and 0% on days 6 and 7 with TRF, the difference being significant on days 2, 5, 6 and 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087802 TI - The radioimmunoassay of bovine and human follicular fluid and serum inhibin. AB - A radioimmunoassay for inhibin in bovine and human follicular fluid (bFF, hFF) and serum from both species was developed based on an antiserum raised in a rabbit to purified bovine 58 kDa inhibin. Following immunization, parallel changes in plasma FSH and inhibin antibody titre were observed suggesting inhibin neutralization in vivo. The antiserum neutralized bFF, hFF and purified 31 kDa and 58 kDa inhibin activity in an in vitro bioassay system. Purified 58 kDa and 31 kDa inhibin were iodinated using a chloramine-T procedure and the 125I-inhibin purified by elution from Matrex Red A, with the iodinated molecules showing similar physicochemical properties to non-iodinated inhibin. Both tracers were stable in bFF but only 125I-31 kDa inhibin was stable in serum. A second antibody RIA system using either tracer yielded a parallel displacement between purified 31 kDa and 58 kDa inhibin. The cross-reaction in the RIA of inhibin from different species when expressed in terms of their bioactivity was bFF 100%, hFF 30%, ovine FF less than 1% and rat ovarian extract non-detectable. Rat LH and FSH, ovine LH and FSH, hCG, bovine TSH, LHRH, ovalbumin and bovine serum albumin showed less than 0.5% cross-reactivity using either tracer. Similar profiles of both bio- and immunoactive inhibin were observed at each stage of the inhibin purification procedure. The in vitro biological to immunological ratios for a number of purified 31 kDa and 58 kDa inhibin preparations using both tracers in the RIA, ranged from 0.30 to 0.43. The RIA was modified for serum by using 125I 31 kDa inhibin as tracer and an elevated temperature (30 degrees C) to minimize non-specific effects. No detectable activity was determined in steer or human post-menopausal serum whilst bull and human female serum showed parallel dose response curves to their respective follicular fluid standards with circulating levels of 0.9 and 1.1 ng/ml respectively. PMID- 3087803 TI - Ether-linked lysophospholipids initiate insulin secretion. Lysophospholipids may mediate effects of phospholipase A2 activation on hormone release. AB - Phospholipase A2 activation may be a pivotal step in glucose-induced insulin secretion; however, recent studies have focused on only one by-product (arachidonic acid). To examine the possible role of the other by-product (lysophospholipids), the lysoderivatives of alkylacyl- (ether linked) or diacylphospholipids were applied to rat islets in static incubations. 1-O-alkyl-2 lyso-sn-glyceryl-3-phosphorylcholine [lyso-PAF, the precursor of platelet activating factor (PAF)] or lysophosphatidylcholine initiated insulin release at 1.7 mM glucose. Two preparations of PAF itself (0.005-5000 ng/ml) were without effect at 1.7 or 16.7 mM glucose, but PAF was nearly equipotent to lyso-PAF at greater than or equal to 20 micrograms/ml. A precursor-product relationship was suggested because the precursors (alkylacyl- or diacylglyceryl-phosphorylcholine) of all three active metabolites were inactive. The stimulatory effect of lyso-PAF is largely independent of any toxic or lytic effect, being biphasic, reversible, unassociated with impairment of the subsequent physiologic functioning of treated islets, and inhibitable (by Ni2+, La3+, or nordihydroguaiaretic acid but not by other lipoxygenase inhibitors). It also occurred at threshold concentrations at which islet morphology and 51Cr retention were preserved. Furthermore, lyso-PAF induced insulin secretion was markedly impaired by reduced ambient temperature (16 degrees C) or by the impermeant anion isethionate, further implying initiation of true exocytotic granule release and fission. Lyso-PAF (but not arachidonic acid) also circumvented the inhibition of glucose-induced insulin release caused by phospholipase inhibitors. Generation of endogenous lysophospholipids through exogenous application of phospholipase A2 also initiated insulin release, an effect responding to a panel of potential inhibitors identically to that induced by exogenously provided lysophospholipids. We propose that glucose activates phospholipase A2 in the pancreatic islet, leading to the generation of lysophospholipids; the latter may couple energy production to insulin release, at least in part via the promotion of Ca2+ translocation. PMID- 3087804 TI - Effects of intracisternal glucose or insulin injections on glucose homeostasis in cat. AB - The injection of glucose (100 mg) into the cisterna magna of intact anesthetized cats elicited immediate glycosuria and natriuresis without significant changes in blood glucose concentration. Immunoreactive insulin (IRI) increased 140% in plasma, and Na+ concentration decreased in cerebrospinal fluid (CSF). After kidney denervation there was a significant decrease in glucose and Na+ concentrations in urine. Control injections with mannitol did not elicit changes in the studied parameters. Abdominal vagotomy abolished the rise in IRI levels and the decrease in Na+ concentration in CSF. Vagotomy or adrenalectomy also attenuated the glycosuria and the rise in urine Na+ concentration. The intracisternal injection of insulin (0.5 U/kg) caused first, a decrease in glucose concentration in CSF and afterwards a longer latency in plasma. Again, these responses were significantly attenuated when insulin was administered in vagotomized cats. These experiments indicate that the nervous system, through the vagi, adrenal glands, and kidneys, plays an important role in glucose homeostasis after increasing glucose or insulin levels in the CSF above physiologic concentrations. The results obtained with a denervated kidney confirm the participation of nervous system in the effector mechanism that brings the sugar and Na+ into the urine. Evidence is presented for an interrelationship between glucose and Na+ concentrations in blood, urine, and CSF. PMID- 3087805 TI - The outcome of perinatal brain damage: the role of normal neuron loss and axon retraction. PMID- 3087806 TI - Continuing medical education for isolated rural general practitioners--a journal project. AB - County Sligo in the Republic of Ireland is a rural area where general practitioners generally work single-handed and in geographical isolation from library facilities. In order to facilitate access to current medical journals for general practitioners a project was started to supply them with the contents pages of recently received general practice literature from a central medical library. Following telephoned or written requests, reprint articles of interest were forwarded by return post. The detailed costs and analysis of the exercise for one year are included. PMID- 3087807 TI - Legislating pediatric placement. PMID- 3087808 TI - Regulation of bilirubin glucuronide synthesis in primate (Macaca fascicularis) liver. Kinetic analysis of microsomal bilirubin uridine diphosphate glucuronyltransferase. AB - Hepatic bilirubin uridine diphosphate glucuronyl-transferase (UDP glucuronyltransferase) catalyzes the formation of bilirubin monoglucuronides (BMG, C-8 and C-12 isomers) and bilirubin diglucuronide (BDG) from bilirubin and the cosubstrate, UDP-glucuronic acid. Distinctive patterns of bile pigment excretion occur in different species and in pathologic disorders (e.g., Gilbert's syndrome). In normal human and monkey (Macaca fascicularis) bile, the proportion of BDG exceeds that of BMG and the C-8/C-12 BMG isomer ratio approaches unity. To investigate the mechanisms responsible for the patterns of BDG and BMG isomers in bile, we used a radiochemical assay to analyze the kinetics and regulation of bilirubin UDP-glucuronyltransferase in microsomes prepared from monkey liver. The synthesis of BMG from bilirubin was a higher capacity, lower affinity step (Vmax = 295 pmol/mg protein X min, Km = 24 microM) than BDG synthesis from endogenously formed BMG (Vmax = 170 pmol/mg protein X min, Km = 14 microM). This observation was confirmed when biosynthetically prepared BMG was used as substrate. The rate of formation of BDG relative to BMG was modulated by both bilirubin and UDP glucuronic acid concentration, whereas the C-8/C-12 BMG isomer ratio was influenced exclusively by UDP-glucuronic acid concentration. The data obtained with increasing UDP-glucuronic acid concentration did not obey conventional single-site kinetics, suggesting the presence of more than one binding site on the enzyme or a membrane transporter for this nucleotide sugar. These findings demonstrate that microsomal bilirubin UDP-glucuronyltransferase has a greater capacity for BMG than BDG synthesis, and thus support the concept that the decreased BDG/BMG ratio in the bile of patients with reduced hepatic enzyme activity (i.e., Gilbert's syndrome and type II Crigler-Najjar disease) reflects the diminished capacity of the enzyme to synthesize BDG from BMG. Bilirubin and UDP-glucuronic acid concentrations both appear to be pivotal in regulating the synthesis of individual bilirubin glucuronides and hence the patterns of bilirubin conjugates excreted in bile. PMID- 3087809 TI - Ultrasonographic study of gallbladder motility during total parenteral nutrition. AB - Gallbladder sludge during total parenteral nutrition may be related to abnormal gallbladder motility. To test this hypothesis, gallbladder motility was assessed in 15 parenterally fed patients and in 22 controls using ultrasonography. Parenteral infusion was continuous in 10 cases and cyclic in 5 cases (6 PM to 10 AM). Gallbladder was simulated to a cone and gallbladder volume was calculated after ultrasonographic measurement of the greatest length and diameter. Six to 12 gallbladder volume measurements were performed between 8 AM and 11 PM in the parenteral nutrition group. In controls gallbladder volume was measured hourly between 8 AM and 8 PM. Thus maximal diurnal gallbladder volume and maximal diurnal gallbladder emptying, expressed as a percentage of maximum gallbladder volume, were determined. Maximal gallbladder volume was identical in the two groups. Gallbladder emptying was significantly reduced in parenterally fed patients (p less than 10(-9)) during both continuous and cyclic infusion. PMID- 3087810 TI - Human duodenal mucosal bicarbonate secretion. Evidence for basal secretion and stimulation by hydrochloric acid and a synthetic prostaglandin E1 analogue. AB - The factors responsible for prevention of duodenal mucosal injury are not known. This series of experiments was performed to determine whether the human duodenum secretes bicarbonate that could prevent mucosal damage. To isolate a 4-cm segment of proximal (i.e., the duodenal bulb) or distal duodenum free of contamination from either gastric or pancreaticobiliary secretion, or both, methods were developed using occlusive balloons. The test segment was perfused with NaCl (2 ml/min, 37 degrees C) containing [14C]PEG as a nonabsorbable marker, and bicarbonate output was quantitated. Mean (+/- SE) basal proximal duodenal bicarbonate output was 143 +/- 17 mumol/cm X h. A 5-min infusion of 25, 50, and 100 mM HCl directly into the isolated proximal duodenal test segment increased bicarbonate output to 167 +/- 29, 199 +/- 19, and 278 +/- 49 mumol/cm X h, respectively, during the hour after acidification. Distal duodenal acidification (25, 50, and 100 mM) also increased bicarbonate output from the isolated proximal duodenal test segment. A synthetic prostaglandin E1 analogue, misoprostol (1.67 13.3 micrograms/min), infused directly into proximal or distal test segments significantly stimulated bicarbonate outbreak; peak responses were 644 +/- 35 mumol/cm X h and 171 +/- 20 mumol/cm X h (p less than 0.001), respectively. Thus, in humans, the proximal and distal duodenal mucosa secretes bicarbonate at rest; direct acidification of the proximal duodenum stimulates bicarbonate output; acidification of the distal duodenum beyond the isolated test segment also increased proximal duodenal bicarbonate output; and a synthetic prostaglandin E1 analogue stimulated both proximal and distal bicarbonate output; however, distal duodenal bicarbonate output was significantly less, indicating a proximal-to distal gradient in bicarbonate secretion. PMID- 3087812 TI - [Effect of individual donor characteristics and preparation conditions on the intensity of the microaggregation process in preserved blood]. PMID- 3087811 TI - [Mastopathy and breast cancer: is there a typical hormone profile?]. AB - Carcinoma of the breast and mastopathy are statistically correlated with the functioning of the gonads. The authors studied whether in 58 women with carcinoma of the breast and in 36 patients with mastopathy any change was seen in the secretory pattern of gonadal steroids and whether there were any latent changes in the secretion of prolactin and TSH. A group of 43 women with benign gynaecological diseases served as controls. Before making the diagnosis via immediate section for microscopic examination we determined the basal values of prolactin, LH, FSH, TSH and the oestrogen fractions E1, E2, E3, total oestrogens and progesterone. In addition, we measured the increase in prolactin and TSH after stimulation with metoclopramide. Postoperatively this was followed by measuring the basal values of prolactin and TSH and their secretory performance in respect of TRH. All histological diagnoses were made by an experienced pathologist. Examinations were performed under strictly standardised conditions, taking into account stress, circadian variation and the nutritional status. The following group-specific significant results were obtained (p less than 0.05 0.01): Mastopathy: high serum values of all oestrogen fractions and of total oestrogens, high PRL release through MTC stimulation, prolactin secretory effect after MTC in accordance with the degree of severity of epithelial proliferation, early onset of menopause. Carcinoma of the breast: Low PRL and TSH release on MTC stimulation, low progesterone concentrations during the second cycle phase, relatively high serum concentrations of oestradiol during the first cycle phase, PRL basal values increased postoperatively, compared with preoperative values. The results led to the following conclusions: In mastopathy patients there is a connection between high oestrogen concentrations and consecutively high prolactin release. The morphological substrate is represented by an enhanced proliferation of epithelium. In patients with cancer of the breast reduced progesterone concentrations during the second half of the cycle lead us to suspect an increased incidence of luteal insufficiency; in addition, it appears that the daily prolactin secretion rate in this group is on a reduced level. PMID- 3087813 TI - [Rapid assay of blood serum for incomplete Rh antibody in the diagnosis of immuno incompatible pregnancy in Rh-positive women]. PMID- 3087814 TI - Autosomal modifiers of the bobbed phenotype are a major component of the rDNA magnification paradox in Drosophila melanogaster. AB - rDNA magnification in Drosophila melanogaster is defined experimentally as the ability of bb/Ybb- males to produce exceptional progeny that are wild type with respect to rDNA associated phenotypes. Here, we show that some of these bobbed plus progeny result not from genetic reversion at the bb locus but rather from variants at two or more autosomal loci that ameliorate the bobbed phenotype of rDNA deficient males in Drosophila. In doing so we resolve several aspects of a long-standing paradox concerning the phenomenon of rDNA magnification. This problem arose from the use of two genetic assays, which were presumed to be identical, but paradoxically, produced conflicting data on both the kinetics of reversion and the stability of magnified bb+ chromosomes. We resolve this problem by demonstrating that in one assay bobbed-plus progeny arise primarily by genetic reversion at the bobbed locus, whereas in the other assay bobbed-plus progeny arise both by reversion and by an epistatic effect of autosomal modifiers on the bobbed phenotype. We further show that such modifiers can facilitate the appearance of phenotypically bobbed-plus progeny even under conditions where genetic reversion is blocked by magnification defective mutants. Finally, we present a speculative model relating the action of these modifiers to the large increases in rDNA content observed in males undergoing magnification. PMID- 3087815 TI - Quantitative analysis of X chromosome effects on the activities of the glucose 6 phosphate and 6-phosphogluconate dehydrogenases of Drosophila melanogaster. AB - By combining 20 X chromosomes with five autosomal backgrounds, the relative importance of these factors with respect to the activity variations of G6PD and 6PGD in Drosophila melanogaster were investigated. Analysis of variance revealed that there exist significant X chromosome, autosomal background and genetic interaction effects. The effect of the X chromosome was due mainly to the two allozymic forms of each enzyme, but some within-allozyme effects were also detected. From the estimated variance components, it was concluded that the variation attributed to the autosomal background is much larger than the variation attributed to the X chromosome, even when the effect of the allozymes is included. The segregation of the allozymes seems to account for about 10% of the total activity variation of each enzyme. The variation due to the interaction between the X chromosome and the autosomal background is much smaller than variations attributed either to the X chromosome or to the autosomal background. The interaction effect is indicated by the change of the ranking of the X chromosomes for different autosomal backgrounds. Highly significant and positive correlation between G6PD and 6PGD activities was detected. Again, the contribution of the autosomal background to the correlation was much larger than that attributed to the X chromosome. PMID- 3087817 TI - Promoter-probe vectors for the analysis of divergently arranged promoters. AB - A series of plasmid-based promoter-probe vectors has been constructed which are particularly useful for the analysis of divergent control regions. Each vector contains a pair of divergently oriented indicator genes whose expression can be monitored over a wide range by simple assay methods. These genes are separated by different polylinkers. Specifically, the beta-galactosidase gene (lacZ) was employed in combination with either the galactokinase gene (galK) or the alkaline phosphatase gene (phoA). In all cases translational stop codons are present in all three reading frames upstream from the initiation codon. The vectors permit direct detection of promoters--independent of insert orientation--on indicator plates after transformation. Using this vector system, we further characterized the divergent tet control regions of transposon Tn10 and plasmid pBR322. PMID- 3087816 TI - Aphidicolin-resistant mutants of mouse lymphoma L5178Y cells with a high incidence of spontaneous sister chromatid exchanges. AB - Two aphidicolin-resistant cell mutants (AC 12 and AC 41) with a fourfold increase in spontaneous frequency of sister chromatid exchanges (SCEs) were obtained out of over 400 aphidicolin-resistant mutants isolated from mouse lymphoma L5178Y cells. They also exhibited three- to fourfold increases in spontaneous frequency of chromosome aberrations (CAs). To determine whether the high level of SCE frequency in AC 12 is caused by 5-bromodeoxyuridine (BrdUrd) used for visualizing SCEs, the effect of BrdUrd incorporated into DNA on SCE induction was analyzed. The SCE frequencies in AC 12 remained constant at BrdUrd incorporation levels corresponding to 2-90% substitution for thymidine in DNA. In addition, the small amount of BrdUrd incorporated into both daughter and parenteral DNA strands in AC 12 had minimal effect on SCE induction. Furthermore, AC 12 and AC 41 were slightly resistant to BrdUrd with respect to the induction of CAs, the inhibition of cell-cycle progression and the decrease in mitotic activity. These findings suggest that the high incidence of SCEs in AC 12 and AC 41 is formed by their intrinsic defects, not by the effects of BrdUrd used. The analysis of SCE frequencies in hybrid cells between these mutants and the parental L5178Y revealed that the genetic defects in AC 12 and AC 41 appear to be recessive, and that these two mutants belong to the same complementation group. Furthermore, AC 12 belonged to a different complementation group from ES 4, which was isolated previously from L5178Y as an SCE mutant with a twofold higher frequency of spontaneous SCEs. This finding indicates that at least two different genetic defects participate in the formation of the high incidence of spontaneous SCEs in mouse cells. These SCE mutants would provide valuable cell materials for studying the molecular mechanism of SCE formation. PMID- 3087818 TI - Functional analysis of the human tissue-type plasminogen activator protein: the light chain. AB - A pBR322::Rous sarcoma virus(RSV)-based shuttle vector was used to insert fused genes, composed of the amino-terminal portion of the bacterial chloramphenicol acetyltransferase gene (cat) and the entire coding region for the C-terminally derived light (L) chain of human tissue-type plasminogen activator (t-PA) cDNA. Cotransfection of rat 3Y1 cells with pRSVneo DNA and pRSVcat/t-PA DNA yielded stably integrated G418-resistant transfectants which contain unrearranged copies of pRSVcat/t-PA DNA. These transfectants synthesize cat/t-PA L-chain mRNA, apparently correctly initiated and terminated. With the help of an enzyme-linked immunosorbent assay (ELISA), it is demonstrated that these cells produce human t PA antigen. Furthermore, pRSVcat/t-PA L-chain cDNA-containing rat 3Y1 cells synthesize a plasminogen-dependent amidolytic activity which is suppressed by specific anti-human t-PA antibodies. This activity cannot be stimulated by fibrin, a property displayed by native t-PA. It is concluded that the t-PA L chain cDNA contains the complete genetic information for the plasminogen activator activity. PMID- 3087819 TI - DNA methyltransferase genes of Bacillus subtilis phages: comparison of their nucleotide sequences. AB - The phi 3T DNA methyltransferase (Mtase) and most of the SP beta Mtase genes have been sequenced. With the exception of their promoters, no difference was found between the phi 3T and SP beta Mtase genes which code for an enzyme with a Mr of 50 507, consisting of 443 amino acids (aa). Comparison of the deduced aa sequence of the phi 3T/SP beta type Mtase (target specificity: GGCC and GCNGC) with that of the previously established sequence of the SPR Mtase (Buhk et al., 1984) which has the target specificity GGCC and CCGG, reveals strong similarities between these two types of enzymes. There is, however, one striking difference: both the phi 3T/SP beta and the SPR enzymes contain at different positions inserts of 33 aa, which have no homology to each other. We suggest that the methylation specificity unique to each of the two types of Mtases (GCNGC in phi 3T/SP beta; CCGG in SPR) depends on these inserts, while the GGCC-specific modification potential common to all Mtases is determined by structures conserved in both types of enzymes. A DNA fragment of non-modifying phage Z, which shows homology to both flanks of the SPR Mtase gene, was also sequenced. This segment can be described as a derivative of SPR DNA, in which the Mtase gene and sequences at its 5' end have been deleted, with the deletion extending between two direct repeats of 25 bp. PMID- 3087821 TI - Managing GI disorders of aging: noncardiac chest pain and rectal bleeding. AB - Esophageal manometry is crucial in the evaluation of patients suspected of having angina pectoris, but in whom there is no discernible evidence of cardiac disease. A frequent problem is whether to attribute bleeding to a vascular ectasia or to diverticulosis, when bleeding from the lesion is neither demonstrated by angiography nor observed by colonoscopy. This diagnostic difficulty is compounded by the frequent occurrence of both disorders in the elderly. PMID- 3087820 TI - Expression vectors based on the rac fusion promoter. AB - The -35 region of the rrnB P2 promoter and the -10 region of the lacZpo promoter operator were fused to form the strong and regulatable rac promoter. Vectors were constructed that allow the attachment of protein-coding sequences to the beta galactosidase alpha-peptide (LacZ alpha) in any reading frame. By introducing a high-copy-number mutation, the synthesis of a LacZ alpha-chloramphenicol acetyltransferase fusion protein reached more than 60% of total cell protein in Escherichia coli. PMID- 3087822 TI - The Cost of Care Index: a case management tool for screening informal care providers. PMID- 3087823 TI - Informal and formal health and social support systems of black and white elderly: a comparative cost approach. PMID- 3087824 TI - [Biochemical changes in the myocardium in chronic exposure to ethylmercury chloride and trichlorfon]. PMID- 3087825 TI - [Indicators of acid-base equilibrium in the blood of parturients in the light of the principles of physiology of physical exertion]. PMID- 3087827 TI - Food service trends. PMID- 3087828 TI - Thyroxine-binding globulin in spontaneous abortion. AB - Thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), thyroxine (T4), free T4, triiodothyronine (T3) and thyroid-stimulating hormone (TSH) were studied in 144 apparently healthy, euthyroid pregnant women displaying miscarriages. In an additional group of 18 aborting women a frozen blood sample drawn in early pregnancy was similarly analyzed for the thyroid components as well as for human chorionic gonadotropin (HCG). The values were compared to those of normal pregnancies (n = 228) at corresponding intervals. Significantly lower values of TBG were found in the spontaneously aborting group. A significantly lower value of TBG was found to be more predictive concerning spontaneous abortion than that of HCG. PMID- 3087826 TI - Gastric form of alpha chain disease. AB - A case of alpha chain disease, involving the stomach only, is reported in an Algerian man suffering from epigastric pains. Upper digestive tract fibreoptic endoscopy showed two antral ulcers and an ulcerative gastritis pattern, which promptly disappeared with cimetidine treatment. Antral biopsies at a distance from the ulcers, but not of the ulcer crater itself, disclosed a dense infiltration of antral lamina propria by mature or sometimes atypical plasma cells. On transmural surgical antral biopsy, the infiltrate spread to the superficial part of the submucosa. No other localisation of the disease was found in spite of multiple biopsies obtained by endoscopy, with a peroral capsule and during staging laparotomy. The alpha chain disease protein was absent from serum and urine, but found in the gastric juice and in the cytoplasma of the cellular infiltrate (alpha 1 subclass). A complete clinical, endoscopic, histological and immunological remission was observed after a six months' course of oral tetracycline. PMID- 3087830 TI - Beta-2-microglobulin and ferritin values in cerebrospinal fluid of patients with acute leukemia. PMID- 3087829 TI - Cerebrospinal fluid ferritin in human disease. PMID- 3087831 TI - Bone marrow biopsy in chronic myeloid leukemia: significance of some histological parameters. PMID- 3087832 TI - Fatty bone marrow with severe myeloid hypoplasia in idiopathic myelofibrosis. PMID- 3087833 TI - Sequential vincristine, arabinosylcytosine and daunomycin induction therapy in adult acute leukemia. PMID- 3087834 TI - Bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL) in remission. PMID- 3087836 TI - Chronic neutrophilic leukemia: report of a case. PMID- 3087835 TI - Type IV Ehlers Danlos syndrome and factor IX deficiency: a case report. PMID- 3087837 TI - Myelodysplastic syndromes: biologic and clinical aspects. PMID- 3087838 TI - New trends in the biology of B-chronic lymphocytic leukemia. PMID- 3087839 TI - Prognostic significance of serum albumin in Hodgkin's disease. PMID- 3087840 TI - Current treatment of patients with inhibitors to factor VIII. AB - The development of inhibitors against factor VIII or IX in hemophilic or nonhemophilic patients is a relatively rare condition, but basic and clinical studies of these inhibitors have been extremely fruitful and have led to the following: a better understanding of the structure-function relationships of the factor VIII and IX molecules; increased knowledge of the genetic defect in classic hemophilia and hemophilia B; newer insights into antibody formation against clotting factors; and an increased number of therapeutic options for the treatment of patients who have inhibitors to factor VIII or IX. The prevalence of inhibitors to factor VIII:C in the hemophiliac population of the U.S. was obtained in the NHLBI multi-center trial using 1500 patients and is estimated to be 14.5%. The vast majority of these inhibitors occurred in severely affected hemophiliacs less than twenty years of age with factor VIII:C levels of less than 0.03 u/ml. However, occasional older patients or those with F. VIII:C greater than 0.03 u/ml did develop inhibitors. PMID- 3087841 TI - [Experience with the dual energy system in parenteral nutrition]. PMID- 3087842 TI - [The atherogenic aspect of the lipoprotein composition in hemodialysis patients]. PMID- 3087843 TI - [Cafe-au-lait spots in the diagnosis of pheochromocytoma]. PMID- 3087844 TI - [Duodenal diverticulum]. PMID- 3087845 TI - Histopathological changes in the liver tissue of house mouse and common vole during sarcocytosis. AB - The asexual reproduction of Sarcocystis dispersa was studied in the liver of the house mouse. Histopathological examinations revealed infection of parenchymal cells with the parasite and diffuse cellular infiltrations with the presence of polymorphonuclear cells, monocytes and eosinophilic leukocytes. The volume and number of cellular infiltrates increased gradually from day 3 till day 10 p.i. Then appeared necrotic foci and both phenomena reached the maximum on days 10-12 p.i. On days 21-34 p.i., no changes occurred in the tissue and the liver healed without scars. The infection of common vole with Sarcocystis cernae sporocysts caused cellular infiltrations in the liver around the portobiliary veins. The parasite was present from day 3 till day 7 p.i. The histopathological picture of liver changes was similar to that in the house mouse. PMID- 3087846 TI - [Pharmacological studies of Senso (Ch'an Su) containing drugs]. AB - General pharmacological properties of two kinds of Senso-containing drugs were studied. There were no prominent differences in the pharmacological profile between the two prescriptions. Inhibition of writhing (60 mg/kg, p.o.), prolongation of hexobarbital-induced hypnosis, hypothermia, antipyretic effect, and inhibition of acetic acid-induced capillary permeability (600 mg/kg, p.o.) in mice were observed after administration of these drugs. These effects were suggested to originate from cinobufagin, a constituent of Senso. Augmentation of blood sugar level and inhibition of gastric juice secretion (600 mg/kg, p.o.) in rats were also observed after administration of these drugs. These effects were suggested to originate from constituents of Senso other than cinobufagin. Isolated ileum and aorta of guinea pigs and vas deferens and fundus strip preparation of rats contracted, and isolated trachea of guinea pigs relaxed after the application of these drugs. The majority of these effects were suggested to originate from epinephrine-like or serotonin-like compounds, constituents of Senso. PMID- 3087847 TI - [The antiinflammatory effect of EB-382]. AB - This study was conducted to clarify the antiinflammatory profile of EB-382, comparing it with those of ibuprofen and other antiinflammatory agents. EB-382 had a more potent inhibition on the acetic acid-induced intensive mouse intraperitoneal vascular permeability and carrageenin-induced rat hind paw edema, but a less potent inhibition on the ultraviolet-induced guinea-pig erythema and the prostaglandin biosynthesis in vitro than ibuprofen. The inhibition by EB-382 was equipotent to that of indomethacin on carrageenin-induced rat pleurisy and the zymosan air pouch, and it demonstrated a strong inhibition on the kallikrein and zymosan-induced intensive guinea-pig skin vascular permeability. EB-382 had a more effective activity on paper disk-induced granuloma and adjuvant arthritis, and it had a less potent action on the gastric mucosal membrane than ibuprofen. EB-382 had a weak action on histamine-induced rat back skin vascular permeability and heat-induced protein denaturation and hemolysis in vitro, as also shown by other test agents. The above results indicate that EB-382 will be useful as an antiinflammatory agent with a new pharmacological effectiveness besides possessing properties common to other acidic non-steroidal antiinflammatory agents in clinical studies. PMID- 3087848 TI - [Cardiovascular effects of MY-5116 and MY-1250]. AB - The effects of MY-5116, isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2 c]quinoline-2-carboxylate, an anti-allergic drug, and MY-1250, an active metabolite of MY-5116, on the cardiovascular system were studied in dogs, rats and guinea pigs. Orally administered MY-5116 (300 mg/kg) had no effect on the cardiovascular system in anesthetized dogs and conscious rats. In anesthetized dogs, MY-1250 and disodium cromoglycate (DSCG) caused hypotension, bradycardia and reduction of respiration rate from the doses of 3 and 10 micrograms/kg, i.v., respectively. Both drugs showed a tachyphylaxic phenomena which was crossed with each other. MY-1250-induced cardiovascular effects were abolished by bilateral vagotomy. MY-1250 (3-30 micrograms/kg, i.v.) caused a decrease of carotid blood flow, a transient decrease followed by a slight increase of renal blood flow, and a transient increase followed by a slight decrease of femoral blood flow in anesthetized dogs. MY-1250 had no effect on sympathetic ganglion, but increased the contractile force of isolated left atria from guinea pigs at 10(-5) g/ml and increased its rate at 10(-4) g/ml. These positive inotropic and chronotropic effects were not influenced by reserpinization. MY-1250 had no effect on the norepinephrine-induced dose-response curve in isolated rat aorta. PMID- 3087850 TI - [Regulation of immunoglobulin gene expression]. PMID- 3087849 TI - [In vitro culture of mouse embryos for toxicological evaluation. (3): Effect of carcinogens on development of the embryos]. AB - Mouse embryos were collected at the 2 cell or 8 cell stage. The embryos of each stage were exposed to 1 pM-10 nM 4-nitroquinoline-1-oxide (4-NQO) or 1 nM-10 microM N-methyl-nitro-nitrosoguanidine (MNNG) for 24 hr, and cultured to develop to blastocysts within clean medium. Since after exposure to 4-NQO, the appearance of early blastocysts and blastocysts were increased in exposure groups compared with controls, the growth to the 8 cell stage embryo (8-E) appeared to be late in development. Frequency of sister chromatid exchange (SCE) and mitotic index were increased with doses in the blastocysts (2-B) which derived from 2-E. There was little change in the SCE and mitotic index for blastocysts (8-B) which derived from the 8 cell stage embryo (8-E). Cessation of development in the 2 cell stage embryo (2-E) appeared in the 10 microM group during the period of exposure to MNNG. Development to the 8-E stage appeared to be slightly late in the other exposed groups. Thereafter at 48 hr after the initiation of culture, the exposed groups appeared to be more advanced in development than the controls. After this period, developmental rates to blastocysts were increased in the 10-100 nM groups. It appeared that the development of these groups was more advanced. In 2 B after exposure to MNNG, cell counts were dose-responsively increased in the 1 and 10 nM groups. The mitotic index in the 1 to 100 nM groups was higher than the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087851 TI - [Studies on the diagnosis of schistosomiasis japonica. (4). Effects of serum dialysis and anthelmintic treatment of the patients on the determination of COP value with special reference to the black eggs]. AB - Eggs of Schistosoma japonicum were obtained from the livers and intestines of the mice infected subcutaneously 50 cercaria 7 weeks previously. A dialyzing celophane tube containing 1 ml of serum was immersed and stirred in 500 ml NaCl solution with different molar concentrations and dialyzed for 24 hrs at 4C. Thereafter, the sera of infected human and animals were incubated with an equal volume of egg-suspension (average 100 eggs per drop). The results indicated that a close relationship between a decrease in the molar concentration of dialyzing solution and an increase of COP value. COP value in a given dialyzed serum sample was dependent on the molar concentration of the solution and independent of the different salt solution with KCl, CaCl2 and MgCl2. COP values were observed in 44 patients in 12 months after treatment with niridazole. The results were as follows; unchanged 1 case, turned to negative 1 case, moderately decreased 3 cases and marked decreased 39 cases. Re-dialysis of these sera with 0.15 M NaCl solution resulted in the equal COP value in all cases. Blackeggs showed a marked reactivity against antisera in COP test as well as those of normal matured eggs. PMID- 3087852 TI - Circulating thyroid hormones in primates with mild or severe hepatitis following liver transplantation. AB - In order to study the effects of acute immunologically mediated liver disease on circulating thyroid hormones, serum levels of thyroxine (T4, total and free) and triiodothyronine (T3) were measured in 8 baboons before and for 60 days after allogeneic liver transplantation. In 3 animals early rejection and jaundice developed; T4 levels declined as liver function deteriorated. In the 5 tolerant animals liver function was only temporarily deranged without jaundice and there was a consistent early rise in T4 (P less than 0.01) followed by a later fall. T3 concentrations were relatively normal in both groups. The T3 resin uptake test remained virtually unchanged in all animals. Serum T4 and T3 responses to exogenously administered bovine thyrotropin (TSH) were similar in the jaundiced and anicteric animals. We conclude that the early rise in T4 in the tolerant animals was caused by transient increases in thyroid binding globulin in (TBG) while the fall in thyroid hormones in these and in the jaundiced animals was related to a decline in TBG levels. Thyroid responsiveness to TSH is not disturbed by moderately deranged liver function. PMID- 3087853 TI - Insulin activation of glycogen synthase in cultured human fibroblasts is not mediated solely via the insulin receptor. AB - Insulin binds to its specific cell surface receptor in cultured human fibroblasts and also stimulates the conversion of glycogen synthase from the glucose-6 phosphate (G-6-P) dependent to the G-6-P independent form. Although these two processes are tightly coupled in most target tissues for insulin action, in the fibroblast a variety of findings question the relationship of these two events to one another. In human fibroblasts the amount of insulin required to displace half of the 125I-insulin bound to the insulin receptor is 4 ng/ml (6.6 X 10(-10)M), but the activation of glycogen synthase is not maximal until 1-10 micrograms/ml with an ED50 of 30 ng/ml insulin. Antibodies directed against the insulin receptor, which activate glycogen synthase in both fat and muscle, do not stimulate the activation of glycogen synthase in the fibroblast. Fab fragments from anti-insulin receptor antibody compete for insulin binding, but do not inhibit the insulin-stimulated rise in independent activity. The insulin-like growth factor, MSA, which is 1% as potent as insulin in stimulating glucose oxidation in rat fat cells and in inhibiting 125I-insulin binding to human fibroblasts, is 25% as potent as insulin in stimulating glycogen synthase. Proinsulin is 2-10% as potent as insulin, but behaves as a "partial agonist" of insulin action in the fibroblast, i.e. proinsulin is able to elicit only 60% of the maximal response of insulin in the glycogen synthase assay, even at high concentrations. Finally, cell lines from patients with clearly defective insulin receptors exhibit normal insulin dose response curves for the activation of glycogen synthase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087854 TI - Planning psychiatry's future. PMID- 3087855 TI - Inadequate DRG payment threatens burn care. PMID- 3087856 TI - Severity measures won't solve PPS problems. PMID- 3087857 TI - Lysosomal storage in human skeletal muscle. AB - Skeletal muscle is involved symptomatically in two lysosomal storage diseases, acid maltase deficiency and a similar condition in which enzyme levels are normal. Asymptomatic storage in skeletal muscle cells is found in Batten-Kufs' disease (ceroid lipofuscinosis), Fabry's disease, and mannosidosis, as well as in rare patients with an unidentified storage disease. Other cell types (vascular endothelium, smooth muscle, fibroblasts, satellite cells) within the confines of the biopsy specimen may reveal storage in other diseases. The differential diagnosis involves predominantly both normal and abnormal conditions in which acid phosphatase activity is prominent in cells. PMID- 3087858 TI - Tumoral amyloidosis of bone of beta 2-microglobulin origin in association with long-term hemodialysis: a new type of amyloid disease. AB - Amyloid lesions of bone are rare and limited almost exclusively to patients with amyloidosis secondary to plasma cell dyscrasias. The present report describes the cases of two patients receiving long-term hemodialysis (nine and 12 years) who had multiple lytic lesions of bone proved by biopsy to contain an unusual type of amyloid. Results of serum protein electrophoreses and immunoelectrophoreses, as well as bone marrow examinations, were normal. In both cases the amyloid displayed characteristic Congo red affinity and birefringence on polarized light microscopy that was inhibited by potassium permanganate treatment of sections prior to staining. Although this staining reaction was described previously exclusively in AA amyloid (i.e., the material associated with classic secondary amyloidosis), immunoperoxidase staining for AA protein in these cases was negative. Transmission electron microscopy revealed the amyloid fibrils to have unusual curvilinear configurations. Immunoperoxidase staining for beta 2 microglobulin (beta 2m) was positive in the amyloid lesions of both patients at the light microscopic level. Ultrastructural immunohistochemical studies for beta 2m, performed in one case, were positive. Both patients had markedly elevated serum beta 2m levels. By Ouchterlony immunodiffusion, purified beta 2m demonstrated partial identity with purified amyloid protein fractions and a serum constituent. Bone lesions composed of amyloid related to beta 2M probably represent a new subgroup of amyloid disease that may be linked to renal failure and long-term hemodialysis. PMID- 3087859 TI - Schistosomiasis and adenocarcinoma of prostate: a morphologic study. AB - A case of prostatic adenocarcinoma coincident with Schistosoma mansoni infestation of the prostate is documented. To the authors' knowledge, this association has not been reported previously. In view of the presence of numerous eggs within the tumor and the youth of the patient, a possible causal relation is suggested. PMID- 3087862 TI - Effect of recombinant interferon alpha 2 on clinical course of first episode genital herpes infection and subsequent recurrences. AB - Herpes genitalis is an infection associated with considerable morbidity. Acyclovir, though effective, must be taken daily to prevent recurrences. The effects of interferon on this infection were therefore investigated. In a randomised double blind study, 31 patients with first episodes of genital herpes infection were studied to assess the effect of interferon on the presenting episode and on recurrences. Interferon (5 X 10(6) IU) was administered once daily subcutaneously during a five day "treatment" period followed by a three month "maintenance" period (1 X 10(6) IU three times weekly). Interferon had no effect on first episode herpetic attacks. During interferon administration women showed a trend towards reduced healing time and viral shedding in recurrences, but the differences were not significant and no effect was noted in women after administration of interferon. Interferon reduced assessed healing time and viral shedding in recurrences, however, in men (p = 0.05) during interferon administration, and this continued as a trend after treatment. PMID- 3087860 TI - Studies on three rare fragile sites. 2q13, 12q13, and 17p12 segregating in one family. AB - Three fragile sites 2q13, 12q13, and 17p12 were found in one family. In the index case, who was first investigated in 1969 for low birth weight and bilateral inguinal hernia, three tissues were examined, blood, marrow, and skin. Three of the family have been reinvestigated after 17 years. Cultures for sister chromatid exchange (SCE) and the effects of aphidicolin, fluorodeoxyuridine (FUdR), bromodeoxyuridine (BrdU), and methotrexate on the frequency of the fragilities were studied. The mother of the index case who is an obligate carrier for the fragile 2q13 does not express it in folate/thymidine deficient medium. Further studies on her using a lymphoblastoid cell line, showed that there was a reduced level of fragility of 12q13 and 17p12 in B-lymphocytes compared to T-lymphocytes. Excess thymidine and FUdR when added to the lymphoblastoid cell line did not induce the 2q13. These studies also confirm the induction of a range of common fragile sites by treatment with aphidicolin, showing in addition homozygosity for at least 3p14, 6q26, 16q23, and Xp22. There were no detectable increases in the SCE rate between individuals with fragile sites and the five controls tested. There was no history of cancer or phenotypic abnormalities in the family. PMID- 3087861 TI - Randomised observer blind comparative trial of ceftriaxone and penicillin in treating uncomplicated gonorrhoea in men and women. AB - Ceftriaxone is a third generation cephalosporin with a prolonged half life. It was used in doses of 500 mg intramuscularly in 27 men (group 1) and 23 women (group 2) and 250 mg in 48 men (group 3) and 45 women (group 4) with uncomplicated urogenital gonorrhoea. Similar numbers of patients in each group were treated with 2 MIU intramuscular Bicillin (procaine penicillin 1.5 g plus benzylpenicillin 300 mg (Brocades, Weybridge, Surrey, England). Success of treatment was measured as one or two negative cultures after three or more days. The success rate for ceftriaxone was 100% in 19 evaluable men and 19 women treated with 500 mg and in 38 men and 31 women treated with 250 mg, including one infection due to penicillinase producing Neisseria gonorrhoeae (PPNG). Success rates for Bicillin were 90% (19/21) evaluable patients cured in group 1, 100% (19/19) in group 2, 95% (37/39) in group 3, and 92% (33/36) in group 4. Both drugs were well tolerated. Each isolate of N gonorrhoeae isolated was sensitive to 0.05 mg/l or less of ceftriaxone. PMID- 3087863 TI - Selective versus non-selective menus. PMID- 3087865 TI - Stimulation of proliferation of murine lymphocytes by the calcium ionophore A 23187 in the absence of serum: the requirement for thiols. AB - The proliferation of mouse spleen cells and T-lymphocytes, initiated by the calcium ionophore A 23187 was studied by a serum-free culture technique. In contrast to Con A, A 23187 was capable of stimulating cells only if 2 mercaptoethanol, cysteine and glutathione (reduced form), respectively, were present in the culture medium. In the absence of one of these compounds a stimulating activity of A 23187 was observed only with high concentrations of cells (i.e., 10(7)/ml). With glutathione present, the cells could be stimulated only at concentrations of A 23187 which were found to be suboptimal in cultures with 2-mercaptoethanol. Human serum, fetal calf serum and bovine serum albumin shifted the active and optimally stimulating concentrations of A 23187 to higher values. A similar effect was observed with sera- and Con A-treated cells. The effect of sera and albumin was paralleled by a protecting effect of cells against high concentrations of A 23187. PMID- 3087864 TI - T-cell markers in the thymus during methylnitrosourea-induced leukemogenesis. AB - T-cell leukemias were induced in adult BDF1 mice by a single i.v. injection of 50 mg/kg of methylnitrosourea (MNU). During the latency period and in leukemic mice the expression of peanut agglutinin (PNA) receptors, terminal deoxynucleotidyl transferase (TdT) and thymus leukemia antigen (TLm4) in the thymus was studied. First, TLm4-positive thymocytes were found 6 wk after MNU. Further, there was a continuous reduction of the percentage of PNA-positive thymocytes. The expression of TdT remained unaltered late in the latency period and in leukemic mice. Four phenotype patterns could be defined for the expression of TdT and PNA in thymocytes: PNA+ TdT+, PNA+ TdT-, PNA- TdT+ and PNA- TdT-. Thymuses negative for TdT were rare, the majority was PNA+ TdT+. However, thymuses late after MNU treatment and leukemic thymus were PNA- TdT+. The discrepancy in the expression of PNA and TdT as cellular markers in leukemic mice as compared to normal cell populations is discussed. PMID- 3087866 TI - Purification of fibrin-specific monoclonal antibody from ascites fluid by preparative isoelectric focusing. AB - With the increased use of site-directed monoclonal antibodies (MAbs) for the detection and localization of antigens (Ags) in vivo, an efficient, noninjurious MAb purification procedure is essential [1-9]. In this study MAb was purified by both immunoaffinity chromatography (IAFC) and preparative isoelectric focusing (PIEF). For anti-fibrin MAb purified by each method, the purification efficiency, blood clearance, and in vivo localization in thrombi were compared. Blood clearance rates and in vivo localization were determined by a double isotope assay: affinity-purified MAb was labeled with I-125, and PIEF-purified MAb was labeled with I-131. Both were injected intravenously into a dog with an experimentally induced femoral vein thrombus. MAb purified by PIEF had a slightly longer biological T 1/2 resulting in comparably higher thrombus localization. Due to its efficiency, PIEF warrants consideration when purified MAb is desired. PMID- 3087867 TI - Elevated natural killer cytotoxicity in HLA-B8 and HLA-DR3-positive individuals. AB - Increased natural killer cytotoxicity in persons positive for HLA-B8 and HLA-DR3 has been found. It is suggested that linkage disequilibrium between the genes coding for HLA-B8 and HLA-DR3 may have evolved as a result of strengthened immunological surveillance in individuals bearing them, as decrease in the frequency of both these antigens has recently been reported in patients with tumours. PMID- 3087868 TI - Phenotype correction of Ir-genic control of immune response to (T,G)-A-L conjugated to synthetic polyelectrolytes. AB - Experiments in CBA (H-2k) and C57BL/6 (H-2b) strains of mice have shown (T,G)-A-L covalently bound to synthetic polyelectrolytes possessing immunoadjuvant effect to induce a pronounced antibody and cell-mediated immune response irrespective of murine genotype. When conjugated to the polyelectrolytes (T,G)-A-L was also found to acquire the properties of a highly immunogenic thymus-independent antigen. Thus, (T,G)-A-L-synthetic polyelectrolytes conjugates manifested the effects of highly immunogenic thymus-independent antigens inducing a potent Ir-1-independent immune response. It provided for the transformation of genetically low responder individuals into high responder ones. PMID- 3087869 TI - Localization of the rat immunoglobulin heavy chain locus to chromosome 6. AB - We have previously used rat/mouse somatic cell hybrids to localize the rat c-myc gene to chromosome 7 (Sumegi et al. 1983) and the rat immunoglobulin kappa locus to chromosome 4 (Perlmann et al. 1985). We now report that by utilizing rat/mouse somatic cell hybrids, we have localized the rat immunoglobulin heavy chain locus to chromosome 6. PMID- 3087871 TI - Plasmid linked mercury & zinc resistance in Klebsiella pneumoniae. PMID- 3087870 TI - Immune response gene control of the murine antibody response to the phospholipase A2 of honey bee venom. PMID- 3087872 TI - Rapid micro-IHA test with FACL-SRBCs in serodiagnosis of amoebiasis. PMID- 3087873 TI - Competition between valproate & phenytoin for plasma protein binding. PMID- 3087874 TI - Statine-containing dipeptide and tripeptide inhibitors of human renin. AB - Dipeptide and tripeptide derivatives containing a statine residue were synthesized as inhibitors of human renin. ES-305, bis[(1 naphthyl)methyl]acetyl(BNMA)-histidyl-statine 2(S)-methylbutylamide was found to be a highly potent inhibitor of human renin with a Ki value of 1.7 X 10(-9) M. Dipeptide derivatives with the BNMA group at the N-terminal (BNMA-Val-Sta isoleucinol [ES-313], BNMA-Leu-Sta-isoleucinol [ES-316], and BNMA-Nle-Sta isoleucinol [ES-317]) had potencies against human renin that were similar to the potency of ES-305. All these dipeptide derivatives competitively inhibited human renin. The inhibitors were also potent against monkey renin but were less effective against renins from pig, goat, dog, rabbit, and rat. ES-305 had little effect on cathepsin D and pepsin at the concentration of 10(-5) M. The other derivatives showed detectable inhibition of cathepsin D (IC50, 10(-6) - 10(-7) M) and pepsin (10(-5) - 10(-6) M). All the compounds had little or no effect on trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at the concentration of 10(-5) M. Our results indicate that ES-305 is a highly potent and specific inhibitor of human renin. This compound is superior to other, previously described statine-containing renin inhibitors with respect to molecular size and enzyme specificity. PMID- 3087875 TI - The loss of endothelium-dependent vascular relaxation in hypertension. AB - We investigated endothelium-dependent relaxation in rat aortae, using three models of experimental hypertension: deoxycorticosterone and salt; one-kidney, one clip renovascular hypertension; and coarctation. Isolated aortae were contracted with phenylephrine, and relaxation was subsequently induced with acetylcholine or calcium ionophore A23187. Blood vessels denuded of endothelium did not relax in response to acetylcholine or A23187. Blood vessels from animals with high blood pressure had decreased relaxation responses to acetylcholine and A23187, and also to the endothelium-independent vasodilator sodium nitroprusside. Unlike acetylcholine and A23187, however, nitroprusside completely relaxed the blood vessels from the hypertensive animals, though the sensitivity to nitroprusside was much lower in these vessels. Subsequent reversal of hypertension caused a return of endothelium-dependent relaxation. Loss of endothelium-dependent relaxation occurs readily in the aortae with the development of hypertension; this phenomenon appears to be related to elevated pressure. PMID- 3087876 TI - Factors responsible for increased susceptibility of mice to intestinal colonization after treatment with streptomycin. AB - Streptomycin sulfate (5 mg/ml) was added to the drinking water of Swiss white mice. After treatment for 1 week, the mice were challenged orogastrically with 10(8) Pseudomonas aeruginosa cells. The organism failed to multiply in the intestinal tract of either treated or untreated animals, but could be recovered from contents and tissues after 48 h. In a previous study, Salmonella typhimurium was shown to multiply in the intestines of streptomycin-treated but not untreated mice when 10(3) organisms were used as inoculum. Streptomycin administration had little effect on Eh, protein or carbohydrate concentrations of cecal contents, or intestinal motility. However, it caused a statistically significant increase in water content and pH of contents and a decrease in the concentrations of acetic, propionic, butyric, and valeric acids. S. typhimurium multiplied in pooled cecal contents obtained from both streptomycin-treated and untreated animals, but its multiplication rate and total populations were significantly greater in contents from treated animals. P. aeruginosa did not multiply in contents from either treated or untreated mice. Similar results were obtained when the organisms were inoculated into nutrient broth adjusted to simulate the pH levels and volatile fatty acid (VFA) concentrations in cecal contents of treated and untreated mice. The addition of brain heart infusion broth to cecal contents from untreated animals, in concentrations that support multiplication of S. typhimurium and P. aeruginosa, did not reverse inhibition. The addition of VFA to cecal contents from treated animals to equal the concentration in cecal contents from untreated animals caused inhibition of a magnitude observed in cecal contents from untreated animals. The results indicate that VFA operating at the pH level of cecal contents of conventional mice inhibit the multiplication of both S. typhimurium and P. aeruginosa and restrict colonization of the intestine by these organisms. The decrease in VFA concentrations that occurs as a result of streptomycin administration adequately explains the increased susceptibility of treated mice to colonization with S. typhimurium. It does not explain the increased susceptibility of treated mice to P. aeruginosa colonization, however. PMID- 3087877 TI - Expression of Mycoplasma pneumoniae antigens in Escherichia coli. AB - A genomic library of Mycoplasma pneumoniae was generated by using bacteriophage lambda EMBL3 as the vector. Screening of the library for the expression of M. pneumoniae protein antigens with adsorbed anti-M. pneumoniae serum revealed strong reactivity from a third of those clones which contained mycoplasma DNA inserts. Three of the most highly reactive clones were analyzed in detail and found to synthesize discrete mycoplasma proteins. Two carried overlapping fragments of mycoplasma DNA which encoded a protein that was readily detected in Escherichia coli after infection with recombinant bacteriophage. The third clone contained a novel mycoplasma DNA fragment which directed the synthesis of two additional mycoplasma proteins. Further screening of the library with antiserum raised against the major M. pneumoniae adhesin protein P1 (165 kilodaltons [kDa]) yielded one clone which produced an immunologically reactive protein of 140 kDa. Adsorption of anti-P1 serum by this clone selected a population of antibodies that were reactive with M. pneumoniae adhesin P1 (165 kDa). These results demonstrate that immunologically active M. pneumoniae proteins are synthesized in E. coli. PMID- 3087878 TI - Calcium-dependent salivary agglutinin with reactivity to various oral bacterial species. AB - Human parotid agglutinins from three individuals were isolated by adsorption to and desorption from strains of Streptococcus mutans belonging to serotypes a, b, c, d, and e and strains of Lactobacillus casei, Actinomyces viscosus, and Streptococcus sanguis. The desorption was achieved by suspending centrifuged saliva-coated microorganisms in 10 mM phosphate buffer (pH 6.8) containing 0.154 M sodium chloride. After another centrifugation, agglutinin activity was recovered in the supernatants. The L. casei strain was not agglutinated by any of the agglutinin extracts or by saliva, but all the other strains were agglutinated to a variable extent. However, all strains, including the nonagglutinating L. casei strain, adsorbed and desorbed agglutinins active for other strains. The agglutinin extracts from S. mutans serotype c, S. sanguis, and A. viscosus were purified and characterized by electrophoretic and immunological techniques. The purified preparations were positively stained for protein and carbohydrate, and the molecular weights were estimated to be 440,000. All agglutinin extracts needed calcium in the range of 0.1 to 0.5 mM to be active, and for a single strain, all agglutinins gave the same degree of agglutination, indicating that the isolated agglutinins may be of the same molecular species, a hypothesis that was also confirmed by the preliminary characterization of the purified agglutinins. This type of agglutinin, which seems to exert its activity among various bacterial species, could be important in mediating bacterial coaggregation and thus may add to the effect of specific agglutinins in the clearance of bacteria from the human mouth. PMID- 3087879 TI - Analysis of Trypanosoma cruzi antigens bound by specific antibodies and by antibodies to related trypanosomatids. AB - Antigens of the epimastigote stage of Trypanosoma cruzi were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions and examined for their ability to bind antibodies in sera from humans infected with this organism or infected with one or both of the related protozoa Leishmania braziliensis and Leishmania donovani by protein blot analysis and enzyme-linked immunosorbent assay. Most of the antigens were bound by antibodies against each one of the organisms. A group of antigens with Mrs between 31,000 and 21,000 were bound by antibodies against T. cruzi only. These antigens were isolated and used in an enzyme-linked immunosorbent assay for the differential diagnosis of Chagas' disease, with excellent results. All sera from individuals proven to be infected with T. cruzi reacted with the antigens, whereas none of the sera from individuals proven to be infected with L. braziliensis or L. donovani reacted with the antigens, even when tested at a low dilution. Biochemical characterization of the isolated antigens revealed the presence of protein and carbohydrate. The reactivity of the isolated antigens with antibodies was completely abolished by pronase and partially abolished by sodium periodate. Protein blot analysis of sera from mice immunized with the antigens revealed a major large band with an Mr between 31,000 and 21,000 and a minor band with an Mr of 45,000, suggesting sharing of epitopes between antigens of different Mrs. These sera did not agglutinate or lyse live epimastigotes. Indirect immunofluorescent antibody tests with live and dead epimastigotes revealed that antibodies in the sera only bound to Formalin-killed organisms. PMID- 3087880 TI - Comparative analysis of infection and transformation of lymphocytes from African buffalo and Boran cattle with Theileria parva subsp. parva and T. parva subsp. lawrencei. AB - This study compared infection and transformation of peripheral blood mononuclear cells (PBM) of Boran cattle and African buffalo in vitro to determine whether differences occurred which could account for the greater susceptibility of Boran cattle to infection with Theileria parva subsp. parva and T. parva subsp. lawrencei. PBM from buffalo and cattle had a similar percentage of cells which bound T. parva subsp. parva sporozoites (24 to 34%) and in which schizonts developed during the first week after infection (18 to 23%). Using a limiting dilution culture system, it was established, however, that a significantly higher proportion of cattle PBM transformed into continuously replicating cell lines after infection with T. parva subsp. parva than did buffalo PBM. The evidence suggests that the low capacity of T. parva subsp. parva to establish infections in buffalo compared with cattle is related to the lower frequency of buffalo cells which undergo transformation. With T. parva subsp. lawrencei, however, the frequency of transformation of buffalo PBM was higher than that for cattle PBM. The frequency of cells transformed by T. parva subsp. lawrencei, therefore, cannot account for the greater resistance of buffalo to infections with T. parva subsp. lawrencei. Buffalo must have other mechanisms, either innate or acquired, which control infection with T. parva subsp. lawrencei more efficiently than in cattle. PMID- 3087881 TI - Lymphokine-activated-killer-mediated lysis of cells infected with typhus group rickettsiae can be inhibited by OKT3 monoclonal antibody. AB - We examined the ability of monoclonal antibodies directed against lymphocyte surface antigens to block the lysis of typhus group rickettsia-infected cells by lymphokine-activated killer effectors. Lysis was significantly inhibited by OKT3 monoclonal antibody but not by OKT4 or OKT8 monoclonal antibody. PMID- 3087882 TI - A common neisserial antigen evidenced by immunization of mice with live Neisseria meningitidis. AB - Mice immunized with live meningococci developed antibodies directed against various antigens of Neisseria gonorrhoeae and Neisseria meningitidis, as demonstrated by immunoblotting. An antigen of 70 kilodaltons appeared to be common and stable in all gonococcal strains tested and highly immunogenic in mice infected with N. meningitidis. PMID- 3087884 TI - Human IgG antibody responses to grass pollen antigens: effects of immunotherapy and comparison of serum and secretory profiles. AB - IgG antibody responses, induced by individual temperate grass pollen allergens in atopic subjects, have been studied by an SDS-PAGE immunoprecipitation technique. These were shown to be of a complex nature and variable between individuals. Profiles obtained with serum and nasal secretions from the same individual were qualitatively similar. Immunotherapy with a glutaraldehyde-modified grass pollen extract, Pollinex, increased the level of specific IgG to three clinically significant grass pollen allergens but did not markedly change the overall pattern of response. PMID- 3087883 TI - Gamma-interferon-induced inhibition of the growth of Rickettsia prowazekii in fibroblasts cannot be explained by the degradation of tryptophan or other amino acids. AB - We examined the role of amino acid deprivation in gamma-interferon-induced (IFN gamma) suppression of the growth of Rickettsia prowazekii in mouse L929 cells and human fibroblasts by measuring the amino acid pools in untreated and IFN-gamma treated cells. In recombinant IFN-gamma-treated cultures of human fibroblasts, tryptophan was undetectable in both the intracellular pool and the extracellular medium. In contrast, tryptophan was not depleted from the intracellular pool or the extracellular medium of L929 cells treated with recombinant IFN-gamma or crude mouse lymphokines. None of the other amino acids measured was severely depleted in IFN-gamma-treated L929 cells and human fibroblasts. Extracts prepared from IFN-gamma-treated human fibroblasts exhibited indoleamine 2,3-dioxygenase activity, converting tryptophan into products that cochromatographed with N formylkynurenine and kynurenine; however, extracts prepared from untreated human fibroblasts, untreated L929 cells, recombinant IFN-gamma-treated L929 cells, and mouse lymphokine-treated L929 cells did not degrade tryptophan. Human HeLa cells resembled the human fibroblasts in that they degraded tryptophan after IFN-gamma treatment. Similarly, mouse 3T3-A31 cells and mouse embryo fibroblasts resembled mouse L929 cells in that they did not degrade tryptophan. Supplementation of the extracellular medium with additional tryptophan reconstituted the tryptophan pool in mock-infected and R. prowazekii-infected, X-irradiated, IFN-gamma-treated human fibroblasts to values greater than those observed in untreated control cultures. However, reconstitution of the tryptophan pool did not relieve IFN gamma-induced inhibition of rickettsial growth. Addition of kynurenine or N formylkynurenine to rickettsia-infected human fibroblasts at concentrations four times the usual tryptophan concentration did not inhibit growth of R. prowazekii. We conclude that neither tryptophan depletion nor depletion of the other amino acids studied explains the inhibitory effect of IFN-gamma on rickettsial growth in mouse L929 cells. In IFN-gamma-treated human fibroblasts, either tryptophan depletion is not involved in the inhibition of rickettsial growth or tryptophan depletion and some other mechanism(s) together contribute to the inhibition of rickettsial growth. PMID- 3087885 TI - Studies on vascular permeability increasing factors involved in 48-hour homologous PCA in the mouse ear. AB - Several attempts were made to elucidate the possible role of histamine, serotonin, leukotrienes C4 (LTC4) and D4 (LTD4), and prostaglandin E1 (PGE1) as vascular permeability increasing factors involved in 48-hour homologous passive cutaneous anaphylaxis (PCA) in the mouse ear. Increased vascular permeability in the mouse ear caused by the mediator injection or PCA was assessed quantitatively by measuring the amount of extravasated dye. In skin reactions, all of the mediators used in the present study significantly increased vascular permeability. The most potent mediator was serotonin, which increased the vascular permeability from a concentration of 10(-8) g/ml, and the activity was about 100 times higher than that of histamine on a weight basis. Vascular permeability increasing activity of LTC4 was about 10 times higher than that of histamine, and LTD4 and PGE1 were also more potent than histamine. Increases of vascular permeability caused by histamine, serotonin, LTC4 and LTD4 were significantly potentiated by injecting 10(-6) g/ml of PGE1 simultaneously. Histamine-, serotonin- and LTC4-induced skin reactions in the mouse ear were suppressed significantly by the administrations of chlorpheniramine, methysergide and FPL 55712, respectively. In contrast, though chlorpheniramine and methysergide suppressed also mouse ear PCA (about 50 and 40%, respectively), neither FPL 55712, indomethacin nor BW 755C suppressed it. These results strongly suggest that the most important mediator involved in mouse ear PCA is histamine and that serotonin also plays an important role in the increase of vascular permeability caused by PCA. Despite their potent vascular permeability increasing activity LTC4, LTD4 and PGE1 do not seem to play an important role in mouse ear PCA. PMID- 3087886 TI - Comparison of antibody levels and protective efficacy against pneumococci in two immunoglobulin preparations for intravenous use. AB - Passive immunization with modern intravenous immunoglobulin preparations might be used prophylactically in individuals at extreme risk of contracting postsplenectomy sepsis or therapeutically in established infections. Since pneumococci are the predominant causative organisms, we determined antibodies against 14 pneumococcal serotypes in two commercially available immunoglobulin preparations (two batches of each) using enzyme-linked immunosorbent assay. The four batches were remarkably similar in antibody content. Low levels against some clinically important serotypes, i.e. types 3, 8 and 18C were recorded. The protective effect of one batch of each preparation against type 1 pneumococci was documented in splenectomized rats. PMID- 3087887 TI - Mouse IgE-mediated paw anaphylaxis in mice and rats. AB - Anaphylactic swelling is induced in the hind paws of mice and rats by intravenous challenge of antigen 72 h after subplantar injection of mouse IgE-rich antiserum into the paws, and can be quantified rapidly and accurately by measuring paw thickness. The edema model described may serve as an alternative to passive cutaneous anaphylaxis for studying immediate allergic reactions with mouse homocytotropic antibodies and screening potential antiallergic drugs. PMID- 3087888 TI - A computerized system for rapid interpretation of acid/base disorders. AB - Rapid and correct interpretation of arterial blood gas results is necessary in the operating room or intensive care unit. However, manual calculation and interpretation is tedious and prone to error. A computer system consisting of two programs written in BASIC has been created to address these problems. The program uses a series of decisions to arrive at a conclusion. Data generated by the Interpreter may be used by a subsequent program, the Manager, in determining ventilation parameters. PMID- 3087889 TI - Radiosensitization of human tumor cells by alpha-difluoromethylornithine. AB - The effect of polyamine depletion on the radiosensitivity of a human tumor cell line was investigated. CAL 18 A cells, derived from a breast carcinoma, were incubated with alpha-difluoromethylornithine (DFMO)--a specific and irreversible inhibitor of ornithine decarboxylase (ODC)--at a 1 mM or 10-mM concentration for either 1 hr or 24 hr and irradiated thereafter. Survival curves of exponentially growing cells revealed a moderate but significant enhancement of radiosensitivity as compared to untreated irradiated cells. Maximum radiosensitization was observed at a concentration of 10 mM after 1 hr incubation. Plateau-phase cells were used to study the effect of polyamine inhibition on repair of radiation induced potentially lethal damage (PLD). DFMO enhanced the radiation response and significantly inhibited PLD repair in these cells. Measurement of ODC indicated that this enzyme was markedly inactivated upon brief incubation of CAL 18 A cells with DFMO, reflecting a depletion of polyamine synthesis. These results extend findings that have demonstrated enhancement of drug-induced cytotoxicity, and raise the possibility of clinical use of this substance for potentiation of radiation response. PMID- 3087890 TI - Effects of a single dose of polychlorinated biphenyls to infant mice on N nitrosodimethylamine-initiated lung and liver tumors. AB - Polychlorinated biphenyls (PCBs) are widespread, chemically-stable environmental contaminants; some congeners are commonly found in human adipose tissue and breast milk. We investigated the effects of a single dose of one PCB mixture (Aroclor 1254) on tumors initiated by N-nitrosodimethylamine (NDMA), also a common environmental agent. Infant outbred Swiss male mice were treated with NDMA (5 mg/kg) i.p. on the 4th day of life, to initiate lung and liver tumors. Four days later each received a single intragastric dose of PCBs (50, 250, or 500 mg/kg of Aroclor 1254) or oil. Groups were killed 16 and 28 weeks later. At both endpoints the mice given 500 mg/kg PCBs after NDMA developed twice as many lung tumors (alveologenic adenomas) as those treated with NDMA only, a significant difference. The PCBs alone did not cause lung tumors. This is the first demonstration of tumor promotion by PCBs in an extrahepatic organ, and it occurred after a single exposure. There were also complex, multiple effects on NDMA-caused liver tumors (adenomas and carcinomas) and on focal hepatocellular proliferative lesions: PCB treatment after the NDMA was associated with decreased number but increased size of these tumors and foci. All of these changes were accompanied by retention in the bodies of 0.1-6 ppm PCBs, as indicated by gas chromatography with electron capture detection. Of this, 80% or more consisted of 2,4,5,2',4',5'-and 2,3,4,2',4',5'-hexachlorobiphenyls in about equal amounts for periods up to 28 weeks. These results point to a need for both experimental and epidemiological studies of the effect of PCB body burden on tumor development. PMID- 3087891 TI - Quantification and characterization of high-affinity membrane receptors for tumor necrosis factor on human leukemic cell lines. AB - The expression of specific membrane receptors for TNF-alpha was determined on various human leukemic cell lines differing in their sensitivity to the growth inhibitory activity of TNF-alpha. Binding studies with 125I-labelled TNF-alpha indicated specific binding in 8/10 cell lines with approximately 10-fold differences in the quantity of TNF-alpha bound by these distinct cell lines. Scatchard analyses of TNF-binding revealed the existence of high-affinity membrane receptors (Kd 1.5 X 10(-10) M) and approximately 3,000 binding sites/cell on both U937 and K562, representing 2 cell lines with high and low TNF sensitivity, respectively. Disuccinimidyl-suberate cross-linking of receptor bound 125I-TNF-alpha and SDS-PAGE of membrane preparations of either U937 or K562 cells suggest a single receptor protein with an apparent molecular weight of 76 kDa. Comparison of the TNF-alpha binding capacity versus in vitro growth inhibition provides evidence that sensitivity to TNF-alpha is determined both at the level of receptor expression and at a post-receptor level. IFN-gamma strongly enhanced the TNF-alpha-mediated growth inhibition of 3 sensitive cell lines, but had no effect on 7 other leukemic cell lines with little or no TNF sensitivity. No correlation was found between this enhancement of TNF sensitivity and the IFN gamma-mediated increase in TNF-cell membrane receptors, suggesting that IFN-gamma predominantly exerts its synergistic effect distal to TNF-binding. PMID- 3087892 TI - Primary meningococcal pericarditis in a pregnant woman. AB - Pericardial effusion is an unusual complication of meningitis due to Neisseria meningitidis. Primary meningococcal pericarditis without signs of meningitis is rare. Only 18 cases have been described in the literature. The first case was reported in 1939 and the others since 1971. We report a case of primary meningococcal pericarditis in a pregnant woman. Improvement followed prompt antibiotic therapy. Fetal death necessitated abortion by curettage. PMID- 3087893 TI - Depigmented neurofibroma. PMID- 3087894 TI - Chagas' disease. PMID- 3087895 TI - The relationship between morbidity and intensity of Schistosoma mansoni infection in a rural Zambian community. AB - Six hundred and ninety-three individuals from an area endemic for S. mansoni infection had parasitological and physical examinations done. A morbidity questionnaire was also administered to each participant. Among those with S. mansoni infection, there was significant increase in watery diarrhoea, bloody diarrhoea, blood in stool and hepatomegaly. The severity of the disease appears to be directly related to the egg load and therefore these results give further justification for treatment of high intensity age groups in community based chemotherapy programmes designed to reduce morbidity in endemic areas. PMID- 3087897 TI - Quantitative studies on Theileria parva in the salivary glands of Rhipicephalus appendiculatus adults: search for conditions for high infections. PMID- 3087896 TI - Immunohistochemical identification of Langerhans cells in normal epithelium and in epithelial lesions of the uterine cervix. AB - Using the double label indirect immunofluorescence technique we have studied vimentin-positive cells present in normal ecto- and endocervical epithelium, subcolumnar reserve cell hyperplasia, and squamous metaplastic and dysplastic epithelium of the uterine cervix. Monoclonal antibodies to Ia- and T6-antigens were applied in the examination of the expression of these membrane markers by such cells. Our studies reveal the presence of a relatively large number of vimentin-positive and T6-positive (Langerhans) cells in normal ectocervical stratified squamous epithelium, a small number in endocervical columnar epithelium, and a larger number in subcolumnar reserve cell hyperplasia and in immature squamous metaplasia. In this respect, mature squamous metaplastic epithelium shows a great resemblance to normal ectocervical stratified squamous epithelium. In contrast with previous reports in the literature we could only demonstrate small numbers of Langerhans cells in cases of dysplasia. The clinicopathological significance of these findings is discussed. PMID- 3087898 TI - Transcutaneous blood gas monitoring during peritoneal dialysis in the neonate. AB - Transcutaneous oxygen and carbon dioxide were monitored continuously during peritoneal dialysis in an infant with severe idiopathic respiratory distress syndrome requiring mechanical ventilation. These showed marked changes in blood gases occurring in phase with the cycles of dialysis due to interference with ventilatory function by fluid in the peritoneal cavity. This finding has important implications for the management of infants requiring peritoneal dialysis during mechanical ventilation. PMID- 3087899 TI - Radiation sensitization of Bacillus megaterium spores by trans dichlorodiammineplatinum(II). AB - The radiation sensitivity of spores of Bacillus megaterium is markedly increased by transplatin in both N2 and O2, and in a manner suggesting the involvement of hydroxyl radicals in both instances, thus differing mechanistically from its isomer cisplatin. PMID- 3087900 TI - Avoidance of a colostomy by nutritional techniques. AB - Total parenteral nutrition or elemental diet has frequently replaced the use of a proximal stoma. Since 1969, data on patients receiving these non-residue nutritional methods have been collated daily; there were 63 patients where the surgeon believed that a proximal stoma would otherwise have been indicated. In 35 patients, these methods were used prophylactically perioperatively and in 28 patients, they were instituted postoperatively after complications occurred; in both groups, there was a very high rate of successful outcome. Modern nutritional support avoided fecal bulk while maintaining nutrition, and appeared to accomplish the equivalent of a diverting proximal stoma with considerable success in other than Crohn's disease. PMID- 3087901 TI - Metabolism of non-protein energy-substrates in septic rats receiving parenteral nutrition. AB - The influences of sepsis on the metabolism of fatty acid and glucose in rats receiving parenteral nutrition were investigated. The caecum, with its blood supply, was ligated in 10 rats to produce peritonitis and sepsis (septic rats). Twelve rats (control rats) did not undergo this procedure. Five septic rats and six control rats received glucose as a sole nonprotein calorie (septic-glucose rats), and the remaining five septic rats (septic-lipid rats) and six control rats received the same parenteral solution for the first 44 hours, but 25% of the nonprotein calorie was replaced by 10% lipid emulsion for the last 24 hours. At the termination of the parenteral nutrition, 14C-linoleic acid or 14C-glucose was injected as a bolus in the tail vein, and their degradations to 14CO2 and incorporations into the endogenous fat were compared among the three groups. It was demonstrated that the sepsis accelerated the oxidation of fatty acid but did not affect that of glucose. Hepatic lipogenesis with both fatty acid and glucose was accelerated by an infusion of glucose under a septic condition, while it was inhibited by an infusion of lipid emulsion. PMID- 3087902 TI - Dynamics of spermatogenesis, hormonal and immune response of patients suffering from chronic prostatitis and sterility under bitemporal treatment with an ultra high frequency electric field. AB - A new method of treatment of patients with chronic prostatitis and sterility by means of ultra-high frequency (60 W) electric field applied bitemporally has been proposed. During treatment 82% of the patients showed an increase in the number of spermatozoa in 1 ml of ejaculate; the percentage of movable and morphologically normal spermatozoa has increased. Patients with chronic prostatitis and sterility showed in the prostatic secrete before treatment a predominance of B-lymphocytes over T-lymphocytes. After treatment the number of T lymphocytes in the prostatic secrete increased and the content of B-lymphocytes decreased. In the subpopulation of T-lymphocytes the content of T-suppressors increased, the content of T-helpers and O-lymphocytes decreased. At the same time patients with sterility showed an increase in blood testosterone level and an FSH decrease. Out of 67 wives of the patients with sterility 50 reported pregnancy within 6 months after beginning of the treatment. PMID- 3087903 TI - Relationships between serum FSH level and the size of testis in azoospermic patients. AB - Sixty-eight out of 700 patients proved to be azoospermic at our Andrology Clinic between 1981 and 1983. According to the serum FSH level and testis size, three main diagnostic groups were established: 1. patients with occlusion but testis size and FSH level normal; 2. patients with smaller testis size and increased FSH level and primary spermatogenetic disorder; 3. non-palpable testis and increased serum FSH level referring also to testicular disorder. No correlations were found between serum LH and testosterone levels and testicular volume. PMID- 3087904 TI - Arylsulfatase B activity in cultured retinal pigment epithelium: regional studies in feline mucopolysaccharidosis VI. AB - Feline mucopolysaccharidosis VI (MPS VI) is a recessively inherited lysosomal storage disease resulting from a deficiency of arylsulfatase B (ASB). Previous histopathologic findings have indicated that the disease is expressed morphologically in non-pigmented retinal pigment epithelial cells (RPE) in the posterior pole and superior equatorial regions by the accumulation of vacuolated inclusions and eventual cellular hypertrophy, while pigmented regions in the periphery are minimally affected. To determine if the regional and age-dependent variations in disease severity result from differences in residual enzyme activity, primary cultures of feline MPS VI-affected RPE were initiated from defined regions of the eye and maintained in vitro for 14 days. Cultures initiated from nonpigmented areas of affected adult eyes (posterior pole, superior equatorial) were more diseased than those from pigmented (inferior equatorial, peripheral) areas. In the nonpigmented cultures, the disease was expressed by the accumulation of single membrane-bound inclusions and cellular hypertrophy. These inclusions were indistinguishable in their morphologic appearance and distribution from those found in situ. In contrast, the cultures initiated from pigmented areas remained normal or minimally affected. The same spatial disease distribution was present in young affected eyes, but the expression of the disease was much less severe. It is apparent that temporal, spatial, and pigmentation factors were correlated with disease expression in vitro as well as in situ. Arylsulfatase B activity was measured biochemically, and found to be deficient in all regions of young and adult eyes. It was notable that there was no correlation between the level of residual enzyme activity, and the pigmentation or spatial position from which the cells were obtained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087905 TI - Effects of iodoacetic acid on cytoskeleton and adhesiveness of the chick RPE cells in vitro. AB - The retinotoxic, sulfhydryl-binding drug, iodoacetic acid (IAA), affects embryonic chick retinal pigmented epithelial (RPE) cells grown in primary cultures in a reversible, dose-dependent manner. A dose of 5 X 10(-4) M which produces drastic cell shape changes in about 90 min was chosen to study the effects of IAA on the organization of cytoskeleton and adhesiveness in RPE cells. After treatment of cells with IAA microtubules depolymerize and F-actin becomes redistributed from numerous stress fibers to knob-like aggregates. Vinculin is released from focal contacts and adhesions into the cytosol and, at the same time, adhesiveness of the RPE cells to substratum decreases. Since RPE in vitro is susceptible to the action of IAA, it seems possible that also in vivo some of the retinotoxic effects of IAA might be attributed to its damaging influence on the RPE. Thus, the retinotoxic effects of IAA in vivo cannot be solely attributed to the selective degeneration of photoreceptors by this agent. PMID- 3087906 TI - Intermediate filaments in the human retina and retinoblastoma. An immunohistochemical study of vimentin, glial fibrillary acidic protein, and neurofilaments. AB - Fifty-five retinoblastoma specimens were studied by a sensitive immunoperoxidase method to determine the intermediate filament types present in human retina and retinoblastoma. Polyclonal antiserum against vimentin and monoclonal antibodies to glial fibrillary acidic protein (GFAP) and to the 200 kD neurofilament triplet protein were used. In the human retina, Muller's cells coexpressed vimentin and GFAP in most instances, probably as a reactive phenomenon. Surprisingly, the horizontal cells did not stain with any of the antibodies used, and may thus lack intermediate filaments. Also, the meshwork of neural fibers in the inner plexiform layer was unusually sparse. Retinoblastoma cells were found to be devoid of all intermediate filament types studied. The tumors contained, however, vimentin and GFAP in the stromal cells. All neurofilament-positive cells in retinoblastoma apparently derived from infiltrated retina. One retinoblastoma eye was also studied by indirect immunofluorescence microscopy of frozen sections with identical results. PMID- 3087907 TI - Complementary role of whole body scan and serum thyroglobulin determination in the follow-up of differentiated thyroid carcinoma. AB - In 233 patients with differentiated thyroid carcinoma previously treated by total thyroidectomy supplemented, when necessary, with a therapeutic dose of 131I, serum thyroglobulin determinations and whole body scans were simultaneously performed. 82 of the 233 showed local or distant metastases: they were detected by both tests only in 36 cases. In 43 patients thyroglobulin was positive but without pathological concentrations of 131I at whole body scan were observed. The remaining 3 cases were detected on the basis of the positive whole body scan only, without increase in the circulating thyroglobulin. These results suggest that caution should be taken when considering thyroglobulin determination as possible substitutive test of whole body scan in the follow-up of differentiated thyroid carcinoma. However, for optimal sensitivity and reliability the complementary role of the two tests is stressed. PMID- 3087908 TI - A committee consults: the care of an anencephalic infant. PMID- 3087909 TI - DRGs and the ethical reallocation of resources. AB - To allocate resources ethically under DRGs, we need an expanded medical ethics. Appealing to traditional patient-centered principles such as individual beneficence and autonomy will not be sufficient. We also need to take into account the social principles of full beneficence and justice. If marginal benefits must be eliminated, clinicians should not participate in deciding who should get less care but should remain committed to their patients' interests. PMID- 3087910 TI - Sublingual flunarizine: a new effective management of the migraine attack. A comparison versus ergotamine. PMID- 3087911 TI - [Effect of a synthetic detergent (Syndet) on the pH of the skin of infants]. AB - The long- and short-term effects on the skin of infants of a synthetic detergent (syndet) with an acid pH were investigated and compared to ordinary soap. The short-term effect was determined by measuring the skin pH on different parts of the body before and 20 min after washing with syndet. The long-term effect was tested in a second group, in which the infants were washed either with ordinary soap or with syndet for 3 days. The skin pH was measured 4-5 h after washing. The results were evaluated statistically. The results show that for a short time syndet displaces the skin pH towards acid pH in younger infants; however, the skin pH is not influenced in older infants. Syndet keeps the skin pH in the physiological range for a longer time after washing than ordinary soap. PMID- 3087913 TI - A cost-effective surgical program: collaboration among an HMO, hospital, and home care agency. PMID- 3087912 TI - [Amyloidosis of the A-kappa type]. AB - A 73-year-old patient complained of increasing macroglossia and symmetrical enlargement of the submandibular region. A tongue biopsy showed typical deposits of amyloid by Congo red staining and polarization microscopy. Similar deposits were found in biopsy specimens of the submaxillary gland and the rectum. Electron microscopy revealed typical amyloid fibrils. With the indirect immunoperoxidase technique the amyloid was classified as being of immunoglobulin kappa-light-chain origin (A-kappa), because only anti-A kappa, but not anti-A lambda (several antisera of non-overlapping specificity), anti-ASc1 or anti-AF antisera were found to be reactive. Correspondingly, Bence Jones protein of the kappa type was found in the urine. In the bone marrow there was an increase in plasma cells of up to 10%. Cytostatic therapy with melphalan and methylprednisolone seemed to stop the progression of amyloid deposition. PMID- 3087914 TI - Assessing the long-term care needs of the elderly: a community survey. PMID- 3087915 TI - Impact of hormonal contraceptives vis-a-vis non-hormonal factors on the vitamin status of malnourished women in India and Thailand. World Health Organization: Special Programme of Research, Development and Research Training in Human Reproduction. Task Force on Oral Contraceptives. AB - The effects of combined oral contraceptives containing 30 or 50 micrograms ethinyl oestradiol and 150 micrograms levonorgestrel or a 3-monthly injectable preparation depo-medroxyprogesterone acetate (DMPA) on the vitamin status of low income group women from two urban centres in India (Bombay and Hyderabad) and one rural centre in Thailand (Chiang Mai) were examined in a follow-up study over a period of 1 year. The magnitude of malnutrition in the study population vis-a-vis a middle-income reference group was assessed by comparing the baseline data on the two groups. Effects of time-related variables such as lactation and season were also examined by a cross-sectional analysis of the baseline data on the study population. In all three centres the majority of the study population suffered from biochemical riboflavin and/or pyridoxine deficiency even before initiating contraception. Lactation appeared to have an effect on the vitamin status, which varied among the different populations. Seasonal effects were seen, but showed inconsistent trends in the three centres. Both the oral contraceptive pills and DMPA tended to increase serum vitamin A and blood folate. The thiamin, riboflavin and pyridoxine status of the women who were already deficient did not deteriorate further with the use of hormonal contraception, as judged by enzyme saturation tests. Some deterioration in the riboflavin status of the normal women of Hyderabad was seen with the use of oral pills. Women who were biochemically deficient prior to the use of oral contraceptives tended to show some improvement in B-vitamin status, over the 1-year period of hormonal contraception. PMID- 3087916 TI - The role of cytochemistry in human genetic research. AB - The role of cytochemistry in human genetics is reviewed. In basic research, autoradiography and cytochemical staining procedures for DNA, RNA, proteins and other cell constituents have contributed to the understanding of the way DNA is localized, duplicated and translated. The development of new "banding techniques" for the identification of human chromosomes and parts of these together with somatic cell hybridization procedures have significantly contributed to the mapping of the human genome. Cytochemical methods have also been of great help in the elucidation of the responsible molecular defects in Mendelian disorders based on a single gene mutation. The combination of immunological methods and electron microscopical cytochemistry now enables different posttranslational processing defects to be related to various subcellular compartments. Cytochemistry is also likely to be of importance for the direct demonstration of gene mutations using recombinant DNA technology. Examples are given of contributions of cytochemical methods to the early diagnosis and prevention of congenital disorders. The main examples are the early diagnosis of patients with a chromosomal aberration and of carriers with a balanced translocation. Early genetic counseling of couples at risk forms the basis for prevention of subsequent affected children. Cytochemistry also contributes to the early detection of heterozygotes of X linked mutations. Finally, autoradiography and ultramicrochemical procedures have been of great help in improving the prenatal diagnosis of genetic metabolic diseases. PMID- 3087917 TI - The use of cationized ferritin to measure cell surface charge of mouse bone marrow cells by flow cytometry. AB - We have prepared fluorescein isothiocyanate (FITC) conjugates of cationised ferritin (CF) and have investigated the usefulness of this CF-FITC to measure the negative cell surface charge of mouse bone marrow cells by flow cytometry. CF FITC conjugates of low fluorochrome to protein ratios (F/P ratio) gave insufficient fluorescence and/or formed large aggregates when stored. CF-FITC conjugates of high F/P ratios (above 25) bound specifically to bone marrow cells, giving sufficient fluorescence, the intensity of which differed for the different cell types. When stored at -20 degrees C the CF-FITC was stable and could be used over prolonged periods. CF-FITC could be used to selectively enrich for pluripotent stem cells (CFU-S) and granulocyte/macrophage progenitors (CFU-C) by fluorescence activated cell sorting (FACS), although the CF-FITC binding to CFU-S and CFU-C was unexpectedly low. No correlation between CF-FITC fluorescence, cell size and electrophoretic mobility (EPM) was observed of bone marrow cells fractionated by free flow electrophoresis. Neuraminidase treatment to remove negatively charged sialic acid groups from the cell surface resulted in an increased binding of CF-FITC, although the EPM was decreased. The biotin conjugate of CF bound to bone marrow cells and could be visualised by avidin FITC. The relative fluorescence intensity for the individual cell types showed a good correlation with the cell surface charge as determined by the EPM of the different cell types. The mechanism of binding CF-FITC to the cell surface was not by electrostatic interaction of the negative cell surface and positively charged CF because CF-FITC of F/P ratios of above 20 was negatively charged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087918 TI - Quantitative study of enzyme immunocytochemical reactions performed with enzyme conjugates immobilized on nitrocellulose. AB - The nitrocellulose binding assay was used for quantitative studies on the cytochemical reactions for the three enzymes most frequently used in immunocytochemistry. The results show a linear relationship between the amount of enzyme immobilized on nitrocellulose and the amount of the enzyme reaction product. The similar course of the formation of the reaction product after DAB/H2O2 staining for peroxidase immobilized on nitrocellulose and for immunoperoxidase labeled cells indicates a linear relationship between the amount of enzyme-coupled antibodies bound to cells and the amount of enzyme reaction product. Furthermore, a mild acid treatment for the abolition of endogeneous peroxidase activity in tissues and cells applicable to immunoperoxidase staining procedures is proposed. PMID- 3087919 TI - Changes in erythropoiesis due to radiation or chemotherapy as studied by flow cytometric determination of peripheral blood reticulocytes. AB - Flow cytometric determination of time dependent changes of numbers of reticulocytes in peripheral blood were investigated as a parameter for changes in erythropoiesis induced by radiation- or chemotherapy. Rats irradiated or treated with drugs (such as e.g. cyclophosphamide 100 mg/kg, vincristin 0.2 mg/kg, or mitomycin C 1.0 mg/kg) showed clear changes in erythropoietic activity. Reticulocyte numbers decreased rapidly until day 3-4 after treatment; this period was followed by a gradual increase and normal control values were seen at day 8 11. Radiation effects of doses as low 0.5 Gy could be detected in such a way. Similar studies were performed with patients with ovarian tumors treated with cis platinum, a drug that may cause non-immune haemolysis. During prolonged treatment some patients showed increasing numbers of reticulocytes, measured at the first day of each hospitalization period, whereas leucocyte and platelet counts stayed more or less constant. Increasing numbers of reticulocytes generally indicates stimulation of erythropoietic activity of the bone marrow (due to increased blood loss); in this study increasing numbers often preceeded a decrease in hemoglobin values later on. Flow cytometric analysis of reticulocytes is therefore a potentially useful tool to detect changes in erythropoiesis, and considered more sensitive for the early recognition of patients that develop anemia, than hemoglobin measurements only. PMID- 3087920 TI - [Effect of tubal function on the osseous structures of the petrous bone. An animal experiment study]. AB - The influence of tubal dysfunction on the osseous structures of the temporal bone of the guinea pig was studied in nondecalcified acrylic embedded tissue. There was a new formation of bone in stages depending on the duration and intensity of the controlled reduced pressure in the bulla which was checked by tympanometry. We found new bone in the Lamina propria of the mucous membrane. Adjacent osteoblasts produced newly formed trabecular bone, whose structure depended on load. A balance between new formation and absorption of bone resulted from release of the reduced pressure in the bulla. Normal pressure in the bulla was followed by an increased activity of the osteoclasts, but the newly formed bone was never resorbed completely. New phases of dysfunction of the Eustachian tube produced sclerotic zones of ossification in the original bone shaped like onion rings. This osteoneogenesis was not seen in the control group with normal impedance, and in the ears subjected to myringotomy, where operatively induced tubal dysfunction could not produce a reduced pressure in the bulla. The mechanism of new bone formation and absorption depends on structural differences. Its mechanism can be interpreted in the light of Frost's concept of remodelling of bone. These results confirm Wittmaack's theory, that pneumatization is determined by environmental factors. PMID- 3087921 TI - An improved biochemical method for the analysis of HLA-class I antigens. Definition of new HLA-class I subtypes. AB - A simple method is described for the biochemical analysis of HLA class I antigens. It is a modification of a previously published procedure for one dimensional isoelectric focusing (1D-IEF), giving improved resolution and offering larger sample capacity. One million viable cells suffice for analysis, and no more than 25 muCi of radioisotope (35S-methionine) are required. The usefulness of the method is illustrated by the characterization of a total of four biochemically distinct subtypes of HLA-B27, three subtypes of HLA-A24, two subtypes of HLA-A11, three subtypes of HLA-A2, two subtypes of HLA-Bw60, two subtypes of HLA-Bw62, and four subtypes of HLA-B35 in a panel of 24 cells selected for the expression of HLA-B27. We envision that this technique will allow a rigorous classification of HLA-A,B antigens into novel subtypes. Populations of distinct ethnic origin are especially of interest in this regard. This technique might also be used as an additional criterion for the official classification of HLA-A,B antigens. PMID- 3087924 TI - Trypanosomiasis and laryngeal paralysis in a dog. AB - Laryngeal paralysis and trypanosomiasis were diagnosed in a 12-year-old Labrador Retriever. Bilateral vocal fold resection and partial excision of the left aryepiglottic fold resolved the dog's respiratory difficulty. Trypomastigotes resembling Trypanosoma cruzi were seen in blood smears during hospitalization. In spite of treatment with nifurtimox and dexamethasone, the dog died. Histologic examination of tissues did not reveal amastigotes of T cruzi or granulomatous myositis previously described in canine trypanosomiasis reported from North America. The lack of granulomatous myositis and amastigotes in muscle is unusual and suggests a strain variation in the behavior of T cruzi. PMID- 3087923 TI - HLA typing used with cultured amniotic and chorionic villus cells for early prenatal diagnosis or parentage testing without one parent's availability. AB - Like fetal fibroblasts and amniotic fluid cells, cultured chorionic villus cells can also be HLA typed with selected typing sera after preincubation with gamma interferon to promote better antigen expression. A modified procedure now in use would also allow any of these cell types to be tested for the presence or absence of all known HLA A,B,C, and DR antigens with standard preplated typing trays. This procedure was used to confirm that an on-going pregnancy had resulted from the successful in vitro fertilization and implantation of an anonymous donor's ovum and could also be of major use in rape or artificial insemination cases when the identity of the possible father(s) is not known. PMID- 3087922 TI - Functional characterization of infiltrating T lymphocytes in human hepatic allografts. AB - We have employed recently developed techniques in T-cell culturing to study the nature and function of infiltrating hepatic allograft T cells. Using the rationale that intragraft T cells are activated during cell mediated damage to the allograft, we were able to show that these cells would propagate and remain functionally active in the presence of the T-cell growth factor, IL-2. In several instances, phenotypic analysis of cells grown in this manner was very similar to that found within the graft. Both proliferative and cytotoxic responses could be detected from the cultured cell lines. The majority of the proliferative responses were donor-directed and immunogenetic analysis could define donor directed HLA reactivity, to either class I or class II antigens, or both. Monoclonal anti-HLA antibodies inhibition profiles verified the apparent HLA reactivity. In a smaller percentage of cases, only IL-2 responsiveness could be detected, and no HLA reactivity could be determined. Cytotoxicity could be detected against both class I and class II antigens, however, those cells which demonstrated a greater magnitude of donor-directed cytotoxicity appeared to be directed against class I antigens. A significant correlation between donor directed proliferation of biopsy cultured lymphocytes and cellular rejection was found. This model appears to be useful in delineating functions of the intragraft T-cell population during rejection. PMID- 3087925 TI - Toxoplasma-like sporozoa in an aborted equine fetus. AB - Multifocal areas of necrosis and infiltrations of mononuclear cells were seen in lung specimens of an equine fetus aborted 2 months before term. Extracellular and intracellular protozoa were seen in the alveolar tissue. Individual organisms were 4 microns by 2.5 microns, and cyst-like structures were 25 microns by 18 microns. Organisms did not stain with periodic acid-Schiff or by use of the immunoperoxidase and peroxidase-antiperoxidase method for Toxoplasma gondii. Twelve days after abortion, the mare had serum antibody titer of less than 1:10 against T gondii. PMID- 3087926 TI - Effects of intermittent injections of LHRH on secretory patterns of LH and FSH and ovarian follicular growth during postpartum anovulation in suckled beef cows. AB - Changes in numbers of ovarian follicles and coincident secretion of pituitary gonadotropins were characterized in suckled, anovulatory beef cows injected iv with 500 ng of luteinizing hormone-releasing hormone (LHRH) every 2 h for 48 or 96 h, starting 21.4 +/- .4 d after parturition. Two hours after the last injection, all cows were ovariectomized. Compared with saline-injected controls, LHRH had no effect on baseline or overall concentrations of luteinizing hormone (LH) in serum (P greater than .10), but increased (P less than .05) frequency and decreased (P less than .05) amplitude of LH pulses. Luteinizing hormone-releasing hormone increased (P less than .05) baseline concentration of follicle stimulating hormone (FSH) in serum and frequency of FSH pulses, but decreased (P less than .05) pulse amplitude. Overall concentrations of FSH increased 20% (P less than .10). Exogenous LHRH did not affect diameter of the two largest follicles or numbers of follicles 1.0 to 3.9 mm, 4.0 to 7.9 mm or greater than or equal to 8.0 mm in diameter. These data suggest that increasing the frequency of episodic LH and FSH pulses in postpartum cattle by intermittent administration of LHRH did not increase mean circulating levels of LH, or alter size and numbers of ovarian follicles within the 96-h period of injections. Thus, induction of ovulation in anovulatory cows treated with low-dose injections of LHRH cannot be explained on the basis of an increase in mean concentrations of LH or numbers of antral follicles within 96 h after initiation of injections. PMID- 3087927 TI - The effect of environmental temperature on concentrations of thyroxine and triiodothyronine after thyrotropin releasing hormone in steers. AB - Twenty-four Angus X Hereford steers (155 +/- 4 kg) were used to examine thyroid function during exposure to ambient temperatures of 4, 18 and 32 C. Jugular cannulae were inserted after steers were acclimated to individual stalls in environmentally controlled chambers at 18 C for 3 d. The day following cannulation, ambient temperatures were changed 2 C/h for 7 h and serum samples were collected hourly. After steers were exposed to either 4, 18 or 32 C for 1 and 72 h, thyrotropin releasing hormone (TRH; 50 micrograms, iv) was rapidly infused. Serum samples were collected hourly for 8 h after each treatment with TRH and every 8 h for 3 d between treatments. Rectal temperatures and respiratory were greater (P less than .05) in steers exposed to 32 C compared with steers at 4 C. During the change in environmental temperature, the concentrations of thyroxine (T4) and triiodothyronine (T3) over time tended (P less than .10) to decrease in steers exposed to 32 C compared with those at 4 C. Concentrations of T4 and T3 after the second treatment with TRH were significantly less in steers exposed to 32 C compared with those at 4 C. The response of T4 to TRH was reduced (P less than .01) after the second treatment with TRH compared with the first for steers exposed to all three temperatures, whereas, the response of T3 was reduced (P less than .05) after the second treatment with TRH only in steers exposed to 32 C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087928 TI - Endocrine profiles associated with life span of induced corpora lutea in postpartum beef cows. AB - Two experiments were designed to examine whether hormonal profiles were related to luteal life span in pluriparous postpartum anestrous beef cows. Cows (Exp. 1, n = 34; Exp. 2, n = 23) received norgestomet (N) for 9 d or served as controls (C). Each cow received 1,000 IU human chorionic gonadotropin (hCG) 48 h after removal of N (d 0). Blood samples collected every 15 min for 8 h on d -5, 3 and 5 (Exp. 1) or on d -10 and -1 (Exp. 2) were assayed for luteinizing hormone (LH) and follicle stimulating hormone (FSH). Cortisol was determined in hourly samples collected on d -5 and in samples collected every 2 min during suckling on the same day (Exp. 1). Concentrations of 15-keto-13,14-dihydro-PGF2 alpha (PGFM) were determined in samples collected at 15-min intervals for 2 h on d -5, 3, 5 and 10 (Exp. 1). Estradiol-17 beta was measured in samples collected on d -5 (Exp. 1) or on d -10 and -1 (Exp. 2). Life span of induced corpora lutea was longer (P less than .05) in N than C cows. Percentages of N cows in which corpora lutea, formed in response to hCG, exhibited a normal life span were 83% on farm 1 and 25% on farm 2 (Exp. 1), and 90% (Exp. 2), compared with 0% in C cows. Concentrations of FSH were not affected by N but were lower (P less than .05) on d -5 in cows on farm 2 (.6 +/- .1 ng/ml) than in cows on farm 1 (.8 +/- .1 ng/ml). On d -5, a treatment X farm interaction (P less than .05) for mean LH was observed and frequency of pulses of LH was higher (P less than .01) in N than C cows (2.7 +/- .4 vs. .8 +/- .8 pulses/8 h). Neither cortisol nor PGFM was affected by N. Estradiol was increased in d -1 (6.1 +/- .5 vs 2.6 +/- .8 pg/ml; P less than .01) by N. It is suggested that pre-treatment with N enhanced life span of induced corpora lutea, in part, by influencing secretion of LH and development of follicles, but a threshold concentration of FSH was required for N to exert this effect. PMID- 3087929 TI - A note on symbiosis of Legionella pneumophila and Tatlockia micdadei with human respiratory flora. AB - Sixteen micro-organisms, representing clinically important respiratory microflora, were tested for their ability to stimulate the growth of Legionella pneumophila and Tatlockia micdadei in nutritionally-deficient agar media. Nutritional symbiosis, indicated by the appearance of satellite colonies of L. pneumophila or T. micdadei, was observed for H. influenzae and N. meningitidis. This interaction between normal flora and pathogens of the respiratory tract may have clinical relevance in the pathogenesis of Legionnaires' disease and Pittsburgh pneumonia. PMID- 3087930 TI - Decrease in adherence of bacteria and yeasts to human mucosal epithelial cells by noxythiolin in vitro. AB - Adherence of buccal and vaginal isolates of Candida albicans to buccal epithelial cells and the adherence of urine isolates of Escherichia coli and Staphylococcus saprophyticus to uroepithelial cells was quantified by light microscopy. The antimicrobial agent noxythiolin reduced the adherence of these micro-organisms in both exponential and stationary growth phases. Adherence of both the blastospore and pseudohyphal forms of C. albicans was reduced. Treatment of epithelial cells and/or micro-organisms with noxythiolin resulted in decreased adherence. No anti adherence effect was observed with formaldehyde and N-methylthiourea, the degradative products of noxythiolin. PMID- 3087931 TI - Inhibition of hyphal development and kill of Candida albicans blastospores by noxythiolin in vitro. AB - The cidal activity of the antimicrobial agent, noxythiolin, was investigated against a laboratory strain and a fresh isolate of Candida albicans. The order of resistance to noxythiolin was hyphal form (isolate) greater than or equal to 25 degrees C-grown blastospores (isolate) greater than 37 degrees C-grown blastospores (isolate) greater than laboratory strain blastospores. Noxythiolin activity was superior to that of 'equivalent' formaldehyde concentrations. Mycelial transformation in C. albicans was examined by light and scanning electron microscopy and measured in terms of percentage germination and hyphal extension. Noxythiolin, 2.5%, in contact for 30 min prevented germination of the blastospore population whereas the decomposition products, formaldehyde and N methylthiourea, showed no appreciable effect in the expected concentrations. The implications of these results are discussed in relation to the observed clinical efficacy of noxythiolin. PMID- 3087932 TI - Induced release of Bacillus spores from sporangia by sodium sulphate. AB - Incubation of sporulating cultures of Bacillus anthracis, B. cereus, B. subtilis and B. thuringiensis in 1.0 mol/l sodium sulphate markedly increased the release of free spores from sporangia. It is postulated that the release of spores is due to activation of latent autolysins which hydrolyse sporangial cell walls. Sodium sulphate-induced lysis of sporangia represents a novel and highly effective method for the recovery of spores from cultures of Bacillus species. PMID- 3087933 TI - Resistance of Providencia stuartii to chlorhexidine: a consideration of the role of the inner membrane. AB - Spheroplasts of three strains of Providencia stuartii (one sensitive, one moderately sensitive and one resistant to chlorhexidine) were induced by cefoxitin, glycine or a lysozyme-tris-EDTA combination, and their susceptibility to chlorhexidine-induced lysis investigated. Maximum lysis of spheroplasts occurred at a low (2.5-5 micrograms/ml) concentration of chlorhexidine and was greatest with the most sensitive strain, Pv2. The possible role of the inner membrane in chlorhexidine resistance is considered in the light of the findings obtained. PMID- 3087934 TI - Antibacterial effects of ticarcillin/clavulanic acid in animal models of infection. AB - The therapeutic effects produced by ticarcillin plus clavulanic acid were compared with those of ticarcillin and clavulanic acid separately against infections in the mouse caused by beta-lactamase-producing bacteria. The infections studied included a pneumonia model, a local tissue infection and pyelonephritis. The distribution of ticarcillin and clavulanic acid in infected animals was evaluated by measurement of the concentrations of the substances present at sites of infection. The results showed that both ticarcillin and clavulanic acid were well-distributed in the mouse and at the doses employed were present at the sites of infection at concentrations of the same order as those obtained in man after administration of ticarcillin/clavulanic acid formulations (Timentin). The protection of ticarcillin by clavulanic acid from inactivation by the beta-lactamases produced in vivo by Bacteroides fragilis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was demonstrated by the pronounced bactericidal effects produced by the ticarcillin/clavulanic acid combination against the ticarcillin-refractory infections studied. PMID- 3087936 TI - Increases in factor VIII complex and fibrinolytic activity are dependent on exercise intensity. AB - Components of the factor VIII complex increase and activation of the fibrinolytic system occur during exercise. The relation between the duration and intensity of exercise and the relative changes in the VIII complex and fibrinolytic system have not been previously examined. Five healthy male subjects were exercised with three protocols: a graded progressive exercise test to exhaustion on a cycle ergometer with 50-W increments every 4 min, steady-state exercise, 15 min at 5 and 125 W each, and an acute 30-s maximal exercise test on a cycle ergometer. Venous blood samples were drawn at base line, during the last 30 s of each power output in the graded exercise, at 5-min intervals for the steady-state exercise, and for up to 1 h after completion of exercise in all three protocols. At the maximum exercise intensities, increases in plasma lactate concentration ([La]), O2 uptake, and [H+] were observed. Components of the VIII complex [VIII procoagulant, VIII procoagulant antigen, VIII-related antigen (VIIIR:Ag), VIII ristocetin cofactor activity] abruptly rose at only the highest work intensities, whereas the whole blood clot lysis time began to gradually shorten much earlier at low work intensities. There were no qualitative changes in the factor VIIIR:Ag on crossed immunoelectrophoresis nor was there evidence of thrombin generation as determined by fibrinopeptide A generation. We conclude that during exercise the changes observed in the coagulation and fibrinolytic systems are related to the intensity of the exercise, which is reflected by increases in plasma [La] and [H+], and that the fibrinolytic system is activated before the changes in the VIII complex are observed. PMID- 3087935 TI - Influence of body size and gender on control of ventilation. AB - Hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses are influenced by both metabolic activity and hormonal factors. By studying 67 subjects of both sexes, including those at the extremes of stature, we examined the influence of gender, CO2 production (VCO2), O2 consumption (VO2), body surface area (BSA), and vital capacity (VC) on resting ventilation (VE), HVR, and HCVR. We measured resting VE, VO2, and VCO2 and then performed isocapnic progressive hypoxic and hypercapnic ventilatory responses. The effect of stature was reflected in higher VE and metabolic rate (both P less than 0.001) in tall men compared with short men that was ablated by correction for BSA. Perhaps because their heights vary less than those of the men, tall women were not statistically distinguishable from short women in any of these measured parameters. Tall men tended to have greater hypoxic chemosensitivity than short men but this was not significantly different (P = 0.07). Gender affected the control of ventilation in a number of ways. Men had higher VE (P less than 0.05) and metabolic rate (P less than 0.001) than women. Even after correction for BSA men still had higher metabolic rates. Women had higher VE/VCO2 than men (P less than 0.05) and lower resting end-tidal Pco2 (PETCO2) values (P less than 0.05). Both A, the shape parameter of the hyperbolic HVR curve, and HVR determined from mouth occlusion pressure (AP) were greater in women than in men, although only AP reached statistical significance. However, corrections of A for BSA (P less than 0.05), VCO2 (P less than 0.01), and VC (P less than 0.001) amplified these differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3087937 TI - Pulmonary microvascular responses to arachidonic acid in isolated perfused guinea pig lung. AB - We examined the effects of arachidonic acid (AA) on pulmonary hemodynamics and fluid balance in Ringer- and blood-perfused guinea pig lungs during constant-flow conditions. Mean pulmonary arterial (Ppa), venous (Pv), and capillary pressures (Pcap, estimated by the double-occlusion method) were measured, and arterial (Ra) and venous resistances (Rv) were calculated. Bolus AA injection (500 micrograms) caused transient increases (peak response 1 min post-AA) in Ppa, Pcap, and Rv without affecting Ra in both Ringer- and blood-perfused lungs. The response was sustained in blood-perfused lungs. AA had no effect on the capillary filtration coefficient in either Ringer- or blood-perfused lungs. AA stimulated the release of thromboxane B2 and 6-ketoprostaglandin F1 alpha in both Ringer- and blood perfused lungs, but the responses were sustained only in the blood-perfused lungs. Meclofenamate (1.5 X 10(-4) M), a cyclooxygenase inhibitor, abolished the AA-induced pulmonary hemodynamic responses in both Ringer- and blood-perfused lungs, whereas U-60257 (10 microM), a lipoxygenase inhibitor, attenuated the response only in the blood-perfused lungs. In conclusion, AA does not alter pulmonary vascular permeability to water in either Ringer- or blood-perfused lungs. AA mediates pulmonary venoconstriction and thus contributes to the rise in Pcap. The venoconstriction results from the generation of cyclooxygenase-derived metabolites from lung parenchymal cells and blood-formed elements. Lipoxygenase metabolites may also contribute to the vasoconstriction in the blood-perfused lungs. PMID- 3087938 TI - A new method for detecting anaerobic threshold by gas exchange. AB - Excess CO2 is generated when lactate is increased during exercise because its [H+] is buffered primarily by HCO-3 (22 ml for each meq of lactic acid). We developed a method to detect the anaerobic threshold (AT), using computerized regression analysis of the slopes of the CO2 uptake (VCO2) vs. O2 uptake (VO2) plot, which detects the beginning of the excess CO2 output generated from the buffering of [H+], termed the V-slope method. From incremental exercise tests on 10 subjects, the point of excess CO2 output (AT) predicted closely the lactate and HCO-3 thresholds. The mean gas exchange AT was found to correspond to a small increment of lactate above the mathematically defined lactate threshold [0.50 +/- 0.34 (SD) meq/l] and not to differ significantly from the estimated HCO-3 threshold. The mean VO2 at AT computed by the V-slope analysis did not differ significantly from the mean value determined by a panel of six experienced reviewers using traditional visual methods, but the AT could be more reliably determined by the V-slope method. The respiratory compensation point, detected separately by examining the minute ventilation vs. VCO2 plot, was consistently higher than the AT (2.51 +/- 0.42 vs. 1.83 +/- 0.30 l/min of VO2). This method for determining the AT has significant advantages over others that depend on regular breathing pattern and respiratory chemosensitivity. PMID- 3087939 TI - Semistarvation and exercise. AB - Nutritional intake plays an important role in determining metabolic and respiratory demands during both rest and exercise. This study examines the effects in normal subjects of 4 days of semistarvation with 440 kcal/day of intravenously infused dextrose followed by the infusion of 480 kcal/day of amino acids for 48 h on the metabolic and ventilatory response to exercise (1.25, 2.50, and 5.0 kg . m/s.). After 4 days of the dextrose infusion, arterial PCO2 (P less than 0.05), and the ventilatory equivalent for CO2 (VE/VCO2, P less than 0.05) were decreased at rest compared with control measurements made prior to the dextrose infusion. During all three levels of steady-state exercise, arterial PCO2 was significantly lower (P less than 0.05) than observed before the start of the dextrose infusion. The subsequent infusion of amino acids resulted in increases in O2 consumption (V02; P less than 0.05) and minute ventilation (VE; P less than 0.05), a decrease in arterial PCO2 (P less than 0.05), and little change in CO2 production (VCO2) at rest. During low levels of exercise, compared with the values obtained following the 4 days of dextrose infusion, there were larger increases in VE and VO2, whereas VCO2 changed little. Mechanical efficiency (kcal work/kcal energy utilized) during exercise increased after 4 days of dextrose and returned to near control levels with the amino acid infusion. The adaptive response characteristic of semistarvation with dextrose appears to be altered when isocaloric amounts of amino acids are subsequently administered for short periods. PMID- 3087941 TI - Endotoxemia causes increased lung tissue lipid peroxidation in unanesthetized sheep. AB - Our purpose was to determine whether lipid peroxidation of lung tissue, a reflection of O2 radical injury, occurs with endotoxin, and whether the degree of tissue change corresponds with the degree of increased protein permeability. Unanesthetized adult sheep with lung lymph fistulas were given Escherichia coli endotoxin at a dose of 2 micrograms/kg (n = 34). Tissue lipid peroxidation was measured using the thiobarbituric acid assay for malondialdehyde (MDA). The MDA content of lung tissue in nanomoles per gram increased from a control value of 48 +/- 8 to 98 +/- 18 at 5 h postendotoxin (2 micrograms/kg), whereas lung lymph protein transport (Cp), was increased 3- to 4-fold. The MDA content returned to base line with Cp by 24 h postendotoxin. Six sheep given endotoxin were pretreated with 12.5 mg/kg of ibuprofen, and six were infused with dimethylthiourea (DMTU) 0.75 g/kg. With ibuprofen, Cp was only increased 2.5- to 3-fold and MDA was increased to 69 +/- 15 nmol/g. With DMTU, the increase in Cp was comparable to that with endotoxin alone, as was the MDA of lung tissue with a value of 92 +/- 12 nmol/g. The correlation of tissue MDA with Cp in all animals was 0.83. We conclude that lipid peroxidation occurs in lung tissue after a moderately severe endotoxin injury with the degree of change corresponding to the degree of increased Cp. PMID- 3087943 TI - Model analysis of steady-state ventilatory response to CO2 into component factors. AB - A method is described to partition measured values of steady-state ventilatory response into an estimation of the blood flow in the respiratory controller and the sensitivity of the controller to CO2 assuming proportional control. The analysis is derived from the describing equations of a computer model and leads to the definition of a grid of lines emanating from a hypothetical reference point at negative ventilation and zero central nervous system metabolism. Data from the literature reporting differences in CO2 response among normal subjects and changes in resting ventilation and cerebral blood flow with age are reinterpreted from this perspective. Use of a structural model to interpret physiological data is shown to give a different meaning to data reduction in contrast to interpretation using statistical models like regression. PMID- 3087940 TI - Effect of pulmonary arterial PCO2 on slowly adapting pulmonary stretch receptors. AB - We recorded pulmonary stretch receptor (PSR) activity in anesthetized dogs and examined the effect of varying pulmonary arterial PCO2 (PpCO2) in both the naturally perfused and vascularly isolated pulmonary circulations while ventilating the lungs with room air. Steady-state increases in PpCO2 from approximately 25 to 50 Torr and from 50 to 70 Torr decreased PSR activity (impulses/ventilatory cycle) by 15 and 9%, respectively (P less than 0.001). Rapid increases in PpCO2 from approximately 50 to 80 Torr in a right-heart bypass preparation (with pulmonary blood flow constant) decreased PSR activity by 27%. Depression of firing, which was proportionately greater in deflation, was not dependent on changes in lung mechanics. Results show that loading CO2 intravascularly depresses PSR activity, the effects extending above as well as below resting PpCO2. Rapidly increasing PpCO2 above the resting level markedly depresses PSR activity during the transient. We conclude that PSRs may contribute to altered breathing resulting from changes in mixed venous PCO2 over the physiological range. PMID- 3087942 TI - An isolated upper airway preparation in conscious dogs. AB - The purpose of this study was to develop an isolated upper airway preparation in conscious dogs. Each of the four dogs was trained to wear an individually fitted respiratory mask and surgically prepared with two side-hole tracheostomies. After full recovery, one endotracheal tube was inserted caudally into the lower tracheostomy hole and another tube cranially into the upper tracheostomy. When the two endotracheal tubes were connected to a breathing circuit including a box balloon system, the magnitude and pattern of the inspiratory flow through the upper airway were identical to that inhaled spontaneously into the lungs by the dogs, but the gas medium inhaled into the upper airway could be independently controlled. Thus it allowed test gas mixtures to be inhaled spontaneously through an isolated upper airway. One limitation was that the inspired gas remained in the upper airway during expiration, but this can be corrected by a simple modification of the breathing circuit. This preparation was tested in studying the respiratory effects of upper airway exposure to CO2 gas mixtures. Our results showed small but significant reduction in both rate and volume of respiration when the concentration of CO2 gas mixture inhaled through the upper airway exceeded 5%. Irregular breathing patterns were frequently elicited in these dogs by higher concentrations (greater than 12%) of CO2. PMID- 3087944 TI - Development of poultry rapid overnight field identification test (PROFIT). AB - A poultry rapid overnight field identification test (PROFIT) has been developed as a screening test which is practical, economical, and easy to perform and interpret for use in field environments to determine the presence of poultry tissue (chicken and turkey) in raw whole tissue or ground/formulated meat products. The basis of the test is an agar-gel immunodiffusion technique used with a printed template pattern and stabilized reagent paper discs. The test shows adequate sensitivity and specificity for its intended purpose. Key components are stable for at least 1 year if they are stored at refrigerator conditions. The design of the test is such that it can be made commercially available as a complete, stable, test kit suitable for use by any type of inspection program concerned with verification of poultry species in meat and/or poultry products that are subject to regulatory or quality controls. PMID- 3087945 TI - Production and isolation of aflatoxin M1 for toxicological studies. AB - One hundred mg aflatoxin M1 was produced and purified for toxicological studies. Aspergillus flavus NRRL 3251 was cultured on rice to produce aflatoxins B1, B2, M1, and M2, B1 and B2 were separated from M1 and M2 by a normal phase low pressure liquid chromatography (LC) column. M1 was then separated from M2 by a reverse phase low pressure LC column. Recoveries of aflatoxins from the LC columns were about 90%. The purified M1 was confirmed by ultraviolet-visible spectrometry, mass spectrometry, nuclear magnetic resonance spectrometry, optical rotation, and its mutagenicity to Salmonella typhimurium TA98. PMID- 3087946 TI - Mutations specifically affecting ligand interaction of the Trg chemosensory transducer. AB - The Trg transducer mediates chemotactic response to galactose and ribose by interacting, respectively, with sugar-occupied galactose- and ribose-binding proteins. Adaptation is linked to methylation of specific glutamyl residues of the Trg protein. This study characterized two trg mutations that affect interaction with binding protein ligands but do not affect methylation or adaptation. The mutant phenotypes indicated that the steady-state activity of methyl-accepting sites is independent of ligand-binding activity. The mutation trg-8 changed arginine 85 to histidine, and trg-19 changed glycine 151 to aspartate. The locations of the mutational changes provided direct evidence for functioning of the amino-terminal domain of Trg in ligand recognition. Cross inhibition of tactic sensitivity by the two Trg-linked attractants implies competition for a common site on Trg. However, the single amino acid substitution caused by trg-19 greatly reduced the response to galactose but left unperturbed the response to ribose. Thus Trg must recognize the two sugar-binding proteins at nonidentical sites, and the complementary sites on the respective binding proteins should differ. trg-8 mutants were substantially defective in the response to both galactose and ribose. An increase in cellular content of Trg-8 protein improved the response to galactose but not to ribose. It appears that Trg 8 protein is defective in the generation of the putative conformational change induced by ligand interaction. The asymmetry of the mutational defect implies that functional separation of interaction sites could persist beyond the initial stage of ligand binding. PMID- 3087947 TI - Cloning and sequencing of the major intracellular serine protease gene of Bacillus subtilis. AB - A Bacillus subtilis 2.7-kilobase DNA fragment containing an intracellular protease gene was cloned into Escherichia coli. The transformants produced an intracellular protease of approximately 35,000 Mr whose activity was inhibited by both phenylmethylsulfonyl fluoride and EDTA. Introduction of the fragment on a multicopy vector, pUB110, into B. subtilis caused a marked increase in the level of the intracellular protease. The nucleotide sequence of the cloned fragment showed the presence of an open reading frame for a possible proenzyme of the major intracellular serine protease (ISP-I) of B. subtilis with an NH2-terminal 17- or 20-amino-acid extension. The total amino acid sequence of the protease deduced from the nucleotide sequence showed considerable homology with that of an extracellular serine protease, subtilisin. The transcriptional initiation site of the ISP-I gene was identified by nuclease S1 mapping. No typical conserved sequence for promoters was found upstream of the open reading frame. An ISP-I negative mutant of B. subtilis was constructed by integration of artificially deleted gene into the chromosome. The mutant sporulated normally in a nutritionally rich medium but showed decreased sporulation in a synthetic medium. The chloramphenicol resistance determinant of a plasmid integrated at the ISP-I locus was mapped by PBS1 transduction and was found to be closely linked to metC (99.5%). PMID- 3087949 TI - Cloning and nucleotide sequencing of genes for small, acid-soluble spore proteins of Bacillus cereus, Bacillus stearothermophilus, and "Thermoactinomyces thalpophilus". AB - As found previously with other Bacillus species, spores of B. stearothermophilus and "Thermoactinomyces thalpophilus" contained significant levels of small, acid soluble spore proteins (SASP) which were rapidly degraded during spore germination and which reacted with antibodies raised against B. megaterium SASP. Genes coding for a B. stearothermophilus and a "T. thalpophilus" SASP as well as for two B. cereus SASP were cloned, their nucleotide sequences were determined, and the amino acid sequences of the SASP coded for were compared. Strikingly, all of the amino acid residues previously found to be conserved in this group of SASP both within and between two other Bacillus species (B. megaterium and B. subtilis) were also conserved in the SASP coded for by the B. cereus genes as well as those coded for by the genes from the more distantly related organisms B. stearothermophilus and "T. thalpophilus." This finding strongly suggests that there is significant selective pressure to conserve SASP primary sequence and thus that these proteins serve some function other than simply amino acid storage. PMID- 3087948 TI - Sequence and properties of pIM13, a macrolide-lincosamide-streptogramin B resistance plasmid from Bacillus subtilis. AB - We initiated a study of pIM13, a multicopy, macrolide-lincosamide-streptogramin B (MLS) plasmid first isolated from a strain of Bacillus subtilis and described by Mahler and Halvorson (J. Gen. Microbiol. 120:259-263, 1980). The copy number of this plasmid was about 200 in B. subtilis and 30 in Staphylococcus aureus. The MLS resistance determinant of pIM13 was shown to be highly homologous to ermC, an inducible element on the S. aureus plasmid pE194. The product of the pIM13 determinant was similar in size to that of ermC and immunologically cross reactive with it. The MLS resistance of pIM13 was expressed constitutively. The complete base sequence of pIM13 is presented. The plasmid consisted of 2,246 base pairs and contained two open reading frames that specified products identified in minicell extracts. One was a protein of 16,000 molecular weight, possibly required for replication. The second was the 29,000-molecular-weight MLS resistance methylase. The regulatory region responsible for ermC inducibility was missing from pIM13, explaining its constitutivity. The remainder of the pIM13 MLS determinant was nearly identical to ermC. The ends of the region of homology between pIM13 and pE194 were associated with hyphenated dyad symmetries. A segment partially homologous to one of these termini on pIM13 and also associated with a dyad was found in pUB110 near the end of a region of homology between that plasmid and pBC16. The entire sequence of pIM13 was highly homologous to that of pE5, an inducible MLS resistance plasmid from S. aureus that differs from pIM13 in copy control. PMID- 3087951 TI - Genetic transformation of genes for protein II in Neisseria gonorrhoeae. AB - The protein II (PII) outer membrane proteins of Neisseria gonorrhoeae are a family of heat-modifiable proteins that are subject to phase variation, in which the synthesis of different PII species is turned on and off at a high frequency. Transformation of PII genes from a donor gonococcal strain into a recipient strain was detected with monoclonal antibodies specific for the PII proteins of the donor. Individual PII protein-expressing transformants generally bound only one donor-specific PII monoclonal antibody. Recovery of transformants expressing a donor-specific PII protein depended on the PII protein expression state of the donor: the transformed population bound only monoclonal antibodies specific for PII proteins that were expressed in the donor. Colony variants with an altered frequency of switching of PII protein expression were isolated, but the altered switch phenotype did not cotransform with the PII structural gene. These results provide genetic evidence that PII proteins are the products of different genes and that expressed and unexpressed forms of the PII gene are different from each other. PMID- 3087952 TI - Diverse effects of the MalE-LacZ hybrid protein on Escherichia coli cell physiology. AB - The hybrid protein between the periplasmic maltose-binding protein and the cytoplasmic beta-galactosidase (the MalE-LacZ hybrid protein) was previously shown to block the export of envelope proteins when synthesized in large amounts. Now we show that the hybrid protein exerts another major effect on the cell, that is, induction of the heat shock proteins. This latter effect was dependent on the htpR gene product but independent of the function of the signal sequence on the hybrid protein. On the other hand, the previously reported induction of the SecA protein by the hybrid protein was independent of htpR and may be caused by the reduced protein export ability of the cell. The functional htpR gene is essential for viability of the cell in which the basal level of the hybrid protein is synthesized, whereas in the absence of the hybrid protein htpR is dispensable at low temperature. These results indicate that the hybrid protein somehow generates a signal or stress that is similar to what the cell experiences at elevated temperatures. PMID- 3087950 TI - Essential role of small, acid-soluble spore proteins in resistance of Bacillus subtilis spores to UV light. AB - Bacillus subtilis strains containing deletions in the genes coding for one or two of the major small, acid-soluble spore proteins (SASP; termed SASP-alpha and SASP beta) were constructed. These mutants sporulated normally, but the spores lacked either SASP-alpha, SASP-beta, or both proteins. The level of minor SASP did not increase in these mutants, but the level of SASP-alpha increased about twofold in the SASP-beta- mutant, and the level of SASP-beta increased about twofold in the SASP-alpha- mutant. The growth rates of the deletion strains were identical to that of the wild-type strain in rich or poor growth media, as was the initiation of spore germination. However, outgrowth of spores of the SASP-alpha(-)-beta- strain was significantly slower than that of wild-type spores in all media tested. The heat resistance of SASP-beta- spores was identical to that of wild type spores but slightly greater than that of SASP-alpha- and SASP-alpha(-)-beta- spores. However, the SASP-alpha- and SASP-alpha(-)-beta- spores were much more heat resistant than vegetative cells. The UV light resistances of SASP-beta- and wild-type spores were also identical. However, SASP-alpha(-)-beta- spores were slightly more sensitive to UV light than were log-phase cells of the wild-type or SASP-alpha(-)-beta- strain (the latter have identical UV light resistances); SASP alpha- spores were slightly more UV light resistant than SASP-alpha(-)-beta- spores. These data strongly implicate SASP, in particular SASP-alpha, in the UV light resistance of B. subtilis spores. PMID- 3087953 TI - Growth kinetics of individual Bacillus subtilis cells and correlation with nucleoid extension. AB - The growth rate of individual cells of Bacillus subtilis (doubling time, 120 min) has been calculated by using a modification of the Collins-Richmond principle which allows the growth rate of mononucleate, binucleate, and septate cells to be calculated separately. The standard Collins-Richmond equation represents a weighted average of the growth rate calculated from these three major classes. Both approaches strongly suggest that the rate of length extension is exponential. By preparing critical-point-dried cells, in which major features of the cell such as nucleoids and cross-walls can be seen, it has also been possible to examine whether nucleoid extension is coupled to length extension. Growth rates for nucleoid movement are parallel to those of total length extension, except possibly in the case of septate cells. Furthermore, by calculating the growth rate of various portions of the cell surface, it appears likely that the limits of the site of cylindrical envelope assembly lie between the distal tips of the nucleoid; the old poles show zero growth rate. Coupling of nucleoid extension with increase of cell length is envisaged as occurring through an exponentially increasing number of DNA-surface attachment sites occupying most of the available surface. PMID- 3087954 TI - Intragenic variation by site-specific recombination in the cryptic plasmid of Neisseria gonorrhoeae. AB - Cryptic plasmid DNA of Neisseria gonorrhoeae was found integrated into the gonococcal chromosome in both plasmid-bearing strains and plasmid-free strains. At several chromosomal locations only segments of the plasmid were found. However, in at least two strains an intact copy of the plasmid seemed to be present with the joints between the plasmid and the chromosomal DNA being located within the cppB gene of the cryptic plasmid. The cppB gene was shown to undergo a sequence-specific intragenic deletion. The deletion removed 54 base pairs, representing 18 amino acids, and did not affect the reading frame. It is proposed that the cryptic plasmid integrates into the chromosome and other gonococcal plasmids within this site-specific deletion region. Models for the site-specific recombination are presented. PMID- 3087955 TI - Methyl sterol and cyclopropane fatty acid composition of Methylococcus capsulatus grown at low oxygen tensions. AB - Methylococcus capsulatus contained extensive intracytoplasmic membranes when grown in fed-batch cultures over a wide range of oxygen tensions (0.1 to 10.6%, vol/vol) and at a constant methane level. Although the biomass decreased as oxygen levels were lowered, consistently high amounts of phospholipid and methyl sterol were synthesized. The greatest amounts of sterol and phospholipid were found in cells grown between 0.5 and 1.1% oxygen (7.2 and 203 mumol/g [dry weight], respectively). While sterol was still synthesized in significant amounts in cells grown at 0.1% oxygen, the major sterol product was the dimethyl form. Analysis by capillary gas chromatography-mass spectrophotometry showed that the phospholipid esterified fatty acids were predominantly 16:0 and 16:1 and that the hexadecenoates consisted of cis delta 9, delta 10, and delta 11 isomers. At low oxygen tensions, the presence of large amounts (25%) of cyclopropane fatty acids (cy 17:0) with the methylene groups at the delta 9, delta 10, and delta 11 positions was detected. Although the delta 9 monoenoic isomer was predominant, growth at low oxygen levels enhanced the synthesis of the delta 10 isomers of 16:1 and cy 17:0. As the oxygen level was increased, the amount of cyclopropanes decreased, such that only a trace of cy 17:0 could be detected in cells grown at 10.6% oxygen. Although M. capsulatus grew at very low oxygen tensions, this growth was accompanied by changes in the membrane lipids. PMID- 3087956 TI - Reduced heat resistance of mutant spores after cloning and mutagenesis of the Bacillus subtilis gene encoding penicillin-binding protein 5. AB - Part of the gene encoding penicillin-binding protein 5 from Bacillus subtilis 168 was cloned in Escherichia coli with a synthetic oligonucleotide as a hybridization probe. The gene was designated dacA by analogy with E. coli. The nucleotide sequence was determined, and the predicted molecular mass was 45,594 daltons (412 amino acids). A comparison of the predicted amino acid sequence with that of the E. coli penicillin-binding protein 5 indicated that these enzymes showed about 25% identity. The B. subtilis dacA gene was mutated by integration of a plasmid into the structural gene by homologous recombination. A comparison of the mutant and control strains revealed that (i) the mutant lacked detectable penicillin-binding protein 5, (ii) the D-alanine carboxypeptidase activity of membranes isolated from the mutant was only 5% of that measured in membranes from the control strain, (iii) the mutant cells showed apparently normal morphology only during exponential growth, and after the end of exponential phase the cells became progressively shorter, (iv) the mutant sporulated normally except that the forespore occupied about two-thirds of the mother cell cytoplasm and, during its development, migrated towards the center of the mother cell, and (v) purified mutant spores were 10-fold less heat resistant but possessed normal refractility and morphology. Preliminary chemical analysis indicated that the structure of the cortex of the mutant was different. PMID- 3087957 TI - Unique antibiotic sensitivity of archaebacterial polypeptide elongation factors. AB - The antibiotic sensitivity of the archaebacterial factors catalyzing the binding of aminoacyl-tRNA to ribosomes (elongation factor Tu [EF-Tu] for eubacteria and elongation factor 1 [EF1] for eucaryotes) and the translocation of peptidyl-tRNA (elongation factor G [EF-G] for eubacteria and elongation factor 2 [EF2] for eucaryotes) was investigated by using two EF-Tu and EF1 [EF-Tu(EF1)]-targeted drugs, kirromycin and pulvomycin, and the EF-G and EF2 [EF-G(EF2)]-targeted drug fusidic acid. The interaction of the inhibitors with the target factors was monitored by using polyphenylalanine-synthesizing cell-free systems. A survey of methanogenic, halophilic, and sulfur-dependent archaebacteria showed that elongation factors of organisms belonging to the methanogenic-halophilic and sulfur-dependent branches of the "third kingdom" exhibit different antibiotic sensitivity spectra. Namely, the methanobacterial-halobacterial EF-Tu(EF1) equivalent protein was found to be sensitive to pulvomycin but insensitive to kirromycin, whereas the methanobacterial-halobacterial EF-G(EF2)-equivalent protein was found to be sensitive to fusidic acid. By contrast, sulfur-dependent thermophiles were unaffected by all three antibiotics, with two exceptions; Thermococcus celer, whose EF-Tu(EF1)-equivalent factor was blocked by pulvomycin, and Thermoproteus tenax, whose EF-G(EF2)-equivalent factor was sensitive to fusidic acid. On the whole, the results revealed a remarkable intralineage heterogeneity of elongation factors not encountered within each of the two reference (eubacterial and eucaryotic) kingdoms. PMID- 3087958 TI - Nucleotide sequence and expression of a phosphate-regulated gene encoding a secreted hemolysin of Pseudomonas aeruginosa. AB - A 3.3-kilobase-pair fragment of Pseudomonas aeruginosa DNA containing the phospholipase C (heat-labile hemolysin) gene was sequenced, and the location of the gene was determined. The gene product contains at its NH2 terminus a 38-amino acid sequence which structurally resembles the signal peptides of other secreted proteins but is unusually long and positively charged (6+). The location of the translation start codon was determined by constructing a series of plasmids in which the promoter of a transcription vector was ligated to Pseudomonas DNA containing deletions at the 5' end of the gene. The plasmids were used to transform Escherichia coli, and the resulting clones were assayed for hemolysin activity. In addition, sizes of truncated proteins produced by mutants with translation terminators introduced at specific sites were analyzed in E. coli maxicells. The gene is transcribed, starting just upstream of the hemolysin gene, as an mRNA of approximately 2,800 bases. Analysis of the nucleotide sequence, analysis of mutants in maxicells, and transcriptional studies indicate that the hemolysin is part of an operon composed of two genes. Phosphate regulation of the operon is at the transcriptional level. The location of the 5' end of the transcript was determined by S1 mapping. PMID- 3087961 TI - Myxococcus xanthus autocide AMI. AB - Autocide AMI of Myxococcus xanthus was purified and shown to be a mixture of fatty acids: 46.4% saturated, 49.3% monounsaturated, and 4.3% diunsaturated. The specific autocidal activities (units per milligram) were as follows: purified AMI, 1,000; saturated fraction, 100; monounsaturated fraction, 800; diunsaturated fraction, 2,200. Model fatty acids mimicked to some extent the activity of AMI, although none of the fatty acids tested were as active as purified AMI. Spontaneous and induced mutants of M. xanthus were selected for resistance to AMI and to fatty acids. The AMI-resistant mutants were also resistant to the model fatty acids, whereas resistance to fatty acids was specific to the compound used for mutant selection. All AMI- and fatty acid-resistant mutants examined were found to be blocked in fruiting body formation. Some of these mutants were able to form normal fruiting bodies when mixed with the extracellular fluid of the parental strain. The data suggest that AMI plays a role in developmental lysis of M. xanthus. PMID- 3087959 TI - Incorporation and modification of exogenous phosphatidylcholines by mycoplasmas. AB - The uptake and modification of exogenous phosphatidylcholine (PC) by several Mycoplasma and Spiroplasma species was investigated. While in most Mycoplasma species and in all Spiroplasma species tested the PC appears to be incorporated unchanged from the growth medium, the PC of M. gallisepticum, M. pulmonis, and M. pneumoniae was disaturated PC, apparently formed by modification of 1-saturated-2 unsaturated PC from the growth medium. The modification of the exogenous PC by M. gallisepticum was inhibited by chloramphenicol under conditions that did not affect de novo synthesis of phosphatidylglycerol. A low activity of an endogenous phospholipase A was detected in native M. gallisepticum membranes. The activity was markedly stimulated by treating the membranes with low concentrations of the nonionic detergents. The PC modification was affected by the fatty acid composition of the exogenous PC species. Diunsaturated, 1-saturated-2 unsaturated, and 1-unsaturated-2-saturated PCs were modified to various extents, whereas the disaturated dipalmitoyl PC (DPPC) was not. Both modified and unmodified PCs were incorporated by the cells, but the unmodified DPPC was incorporated at a lower rate and to a lesser extent. The possibility that the incorporation of DPPC into M. gallisepticum cells is associated with the formation of intracytoplasmic membranes is discussed. PMID- 3087960 TI - Characterization of iucA and iucC genes of the aerobactin system of plasmid ColV K30 in Escherichia coli. AB - A cloned 8.3-kilobase-pair DNA fragment carrying all the genes (iucABCD iutA) of the aerobactin iron transport system of plasmid pColV-K30 was subjected to in vitro mutagenesis to afford mutant genes iucA, iucC, and iucA iucC. Complementation analyses and identification of aerobactin precursors accumulated by Escherichia coli cells harboring the different constructions allowed assignment of the iucA and iucC genes to discrete steps in biosynthesis of the siderophore from N epsilon-acetyl-N epsilon-hydroxylysine and citrate. Plasmid pVLN10, a derivative carrying a DNA fragment complementing an iucC mutation, expressed in a minicell system a single 62,000-dalton protein as the product of this gene. PMID- 3087962 TI - Nonrandom cosmid cloning and prophage SP beta homology near the replication terminus of the Bacillus subtilis chromosome. AB - From a library of Bacillus subtilis DNA cloned with the Escherichia coli cosmid vector pHC79, 85 recombinant cosmids containing DNA from near the replication terminus, terC, were identified. The DNA inserts of these cosmids were confined to three regions of a 350-kilobase segment of the chromosome extending from the left end of the SP beta prophage to approximately 75 kilobases on the right of terC. All B. subtilis genes known to reside in this segment, as well as the portion of the SP beta prophage that is expressed early in the lytic cycle of the phage, appeared to be absent from the library. A region of SP beta homology distinct from the prophage and just to the left of terC was identified. PMID- 3087963 TI - Identification of a carotenoid-binding protein in the cytoplasmic membrane from the heterotrophic cyanobacterium Synechocystis sp. strain PCC6714. AB - We isolated a carotenoid-binding protein from the cytoplasmic membrane of the cyanobacterium Synechocystis sp. strain PCC6714. The polypeptide demonstrated a characteristic mobility shift when electrophoresed in lithium dodecyl sulfate polyacrylamide gels. The protein migrated with an apparent molecular mass of 35 kilodaltons when solubilized at 0 degrees C, but after solubilization at 70 degrees C, the protein migrated as a 45-kilodalton species. The carotenoid binding protein accumulated only in autotrophically grown cells; cytoplasmic membranes prepared from photoheterotrophically grown cells lacked this component. PMID- 3087964 TI - Expression of luciferases from Vibrio harveyi and Vibrio fischeri in filamentous cyanobacteria. AB - Shuttle vectors that had previously been shown to replicate both in Escherichia coli and in strains of Anabaena spp. were used to transfer the lux genes from Vibrio harveyi and Vibrio fischeri into Anabaena spp. The level of expression of luciferase in the cyanobacteria (up to 7,000 quanta cell-1 s-1) makes these genes good candidates for use as promoter probes during the differentiation of certain cells in a filament into heterocysts. PMID- 3087965 TI - Regulatory mutation that controls nif expression and histidine transport in Azospirillum brasilense. AB - Mutagenesis of Azospirillum brasilense with nitrosoguanidine and selection on ethylenediamine yielded prototrophs which fixed nitrogen in the presence of ammonia. Nitrogenase activity in mutant strains exceeded that of the wild type three- to sixfold. The same mutants were also constitutive for histidine transport. Enzyme activities involved in ammonia assimilation were not affected by the mutation. The data suggest that the mutation occurred at a site which regulates nif and histidine transport functions. PMID- 3087966 TI - Mapping of mutations in Pseudomonas aeruginosa defective in pyoverdin production. AB - Twelve mutants of Pseudomonas aeruginosa PAO defective in pyoverdin production were isolated (after chemical and transposon mutagenesis) that were nonfluorescent and unable to grow on medium containing 400 microM ethylenediaminedi(o-hydroxyphenylacetic acid). Four mutants were unable to produce hydroxamate, six were hydroxamate positive, one was temperature sensitive for pyoverdin production, and another was unable to synthesize pyoverdin on succinate minimal medium but was capable of synthesizing pyoverdin when grown on Casamino Acids medium (Difco Laboratories, Detroit, Mich.). The mutations were mapped on the PAO chromosome. All the mutations affecting pyoverdin production were located at 65 to 70 min, between catA1 and mtu-9002. PMID- 3087967 TI - Immunocytochemical ultrastructural analysis of chromatophore membrane formation in Rhodospirillum rubrum. AB - An immunocytochemical ultrastructural study of Rhodospirillum rubrum cultured under semiaerobic conditions was conducted to correlate the localization of functional components with membrane formation. R. rubrum is a facultatively phototrophic organism. Under reduced oxygen, this bacterium forms an intracytoplasmic chromatophore membrane that is the site of the photosynthetic apparatus. Immunogold techniques were used to localize intracellular protein antigens associated with the photosynthetic apparatus. Antibody, demonstrated by immunoblotting to be specific for the reaction center and light-harvesting photochemical components, was conjugated to colloidal gold particles and used for direct immunolabeling of fixed, sectioned specimens. Membrane invaginations appeared by 4 h after transition to induction conditions, and mature chromatophore membrane was abundant by 22 h. The occurrence of chromatophore membrane was correlated with bacteriochlorophyll a content and the density of the immunolabel. In uninduced (aerobic) cells and those obtained from cultures 0.5 h posttransition, the immunogold preferentially labeled the peripheral area of the cell. In contrast, in cells obtained after 22 h of induction, the central region of the cell was preferentially immunolabeled. These findings provided immunocytochemical evidence supporting the hypothesis that the chromatophore membrane is formed by invagination of the cytoplasmic membrane. PMID- 3087968 TI - Antidepressant drug therapy for bulimia: current status. AB - More than 30 reports, including 9 placebo-controlled, double-blind studies, have assessed the efficacy of various medications, mostly antidepressants, for the treatment of bulimia. A critical review of the available data suggests that antidepressants, and possibly other thymoleptic agents, are clearly superior to placebo for the treatment of bulimia; the studies have not identified specific subgroups of bulimic patients who are, or are not, candidates for these agents; and tentatively, these agents may benefit major affective disorder and bulimia via similar mechanisms. PMID- 3087969 TI - c-fos and c-myc gene activation, ionic signals, and DNA synthesis in thymocytes. AB - Among the earliest responses to mitogens that have been detected in normal quiescent cells are ionic changes: we have described rapid increases in the cytosolic free Ca2+ concentration ([Ca]i) and in the intracellular pH (pHi) in mitogen-stimulated thymocytes and fibroblasts (Hesketh, T. R., Moore, J. P., Morris, J. D. H., Taylor, M. V., Rogers, J., Smith, G. A., and Metcalfe, J. C. (1985) Nature 313, 482-484). Here we investigate the relationship between these ionic signals and the subsequent expression of the c-fos and c-myc proto oncogenes in murine thymocytes. We show that the plant lectin concanavalin A (ConA), the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) and the Ca2+-ionophore A23187 each causes a rapid increase in both c-fos and c-myc mRNAs. The activation of both genes is completely dependent on the extracellular Ca2+ concentration ([Ca]o) for A23187 and independent of [Ca]o for TPA. Activation of c-myc, but not c-fos, by ConA is partially dependent on [Ca]o. The pHi increases generated by ConA or TPA are not necessary for expression of mRNA from either gene in response to these mitogens. Exogenous 8-bromo-cyclic AMP (but not 8-bromo cyclic GMP) inhibits the c-myc responses to ConA and TPA. The data also show that neither early c-fos nor c-myc expression is sufficient to commit the cells to DNA synthesis. PMID- 3087970 TI - Two guanine nucleotide-binding proteins in rat brain serving as the specific substrate of islet-activating protein, pertussis toxin. Interaction of the alpha subunits with beta gamma-subunits in development of their biological activities. AB - Two proteins serving as substrates for ADP-ribosylation catalyzed by islet activating protein (IAP), pertussis toxin, and binding guanosine 5'-(3-O thio)triphosphate (GTP gamma S) with high affinities were purified from the cholate extract of rat brain membranes. The purified proteins had the same heterotrimeric structure (alpha beta gamma) as the IAP substrates previously purified from rabbit liver and bovine brain and differed from each other in alpha only; the molecular weight of alpha was 41,000 (alpha 41 beta gamma) and 39,000 (alpha 39 beta gamma). Both were further resolved into alpha (alpha 41 or alpha 39) and beta gamma which were also purified to homogeneity to compare the activities of alpha-monomers with the original trimers. The maintenance of the rigid trimeric structure by combining alpha 41 or alpha 39 with beta gamma in the absence of Mg2+ was essential for the alpha-subunit to be ADP-ribosylated by IAP. The alpha-subunit was very stable but displayed the only partial GTP gamma S binding activity under these conditions. Isolated alpha-monomers exhibited high GTPase activities when assayed in the presence of submicromolar Mg2+ but were very unstable at 30 degrees C and not ADP-ribosylated by IAP. The most favorable conditions for the GTP gamma S binding to alpha-subunits were achieved by combining alpha 41 or alpha 39 with beta gamma in the presence of millimolar Mg2+, probably due to the increase in stability and unmasking of the GTP-binding sites. There was no qualitative difference in these properties between alpha 41 beta gamma (alpha 41) and alpha 39 beta gamma (alpha 39). But alpha 39 beta gamma (or alpha 39) was usually more active than alpha 41 beta gamma (or alpha 41), at least partly due to its higher affinity for Mg2+ and lower affinity for beta gamma. Relation of these differences in activity between alpha 41 beta gamma and alpha 39 beta gamma to their physiological roles in signal transduction is discussed. PMID- 3087971 TI - Human acid beta-glucosidase. Use of conduritol B epoxide derivatives to investigate the catalytically active normal and Gaucher disease enzymes. AB - Human acid beta-glucosidase (glucosylceramidase; EC 3.2.1.45) cleaves the glycosidic bonds of glucosyl ceramide and synthetic beta-glucosides. Conduritol B epoxide (CBE) and its brominated derivative are mechanism-based inhibitors which bind covalently to the catalytic site of acid beta-glucosidase. Procedures using brominetritiated CBE and monospecific anti-human placental acid beta-glucosidase IgG were developed to determine the molar concentrations of functional acid beta glucosidase catalytic sites in pure placental enzyme preparations from normal sources; kcat values then were calculated from Vmax = [Et]kcat using glucosyl ceramide substrates with dodecanoyl (2135 +/- 45 min-1) and hexanoyl (3200 +/- 410 min-1) fatty acid acyl chains and 4-alkyl-umbelliferyl beta-glucoside substrates with methyl (2235 +/- 197 min-1), heptyl (1972 +/- 152 min-1), nonyl (2220 +/- 247 min-1), and undecyl (773 +/- 44 min-1) alkyl chains. The respective kcat values for acid beta-glucosidase in a crude normal splenic preparation were about 60% of these values. In comparison, the kcat values of the mutant splenic acid beta-glucosidase from two Type 1 Ashkenazi Jewish Gaucher disease (AJGD) patients were about 1.5-3-fold decreased and had Km values for each substrate which were similar to those for the normal acid beta-glucosidase. The interaction of the normal and Type 1 AJGD enzymes with CBE in a 1:1 stoichiometry conformed to a model with reversible EI complexes formed prior to covalent inactivation. With CBE, the equal kmax values (maximal rate of inactivation) for the normal (0.051 +/- 0.009 min-1) and Type 1 AJGD (0.058 +/- 0.016 min-1) enzymes were consistent with the minor differences in kcat. In contrast, the Ki value (dissociation constant) (839 +/- 64 microM) for the Type 1 AJGD enzymes was about 5 times the normal Ki value (166 +/- 57 microM). These results indicated that the catalytically active Type 1 AJGD acid beta-glucosidase had nearly normal hydrolytic capacity and suggested an amino acid substitution in or near the acid beta-glucosidase active site leading to an in vivo instability of the mutant enzymatic activity. PMID- 3087972 TI - Induction of digitoxigenin monodigitoxoside UDP-glucuronosyltransferase activity by glucocorticoids and other inducers of cytochrome P-450p in primary monolayer cultures of adult rat hepatocytes and in human liver. AB - We have recently proposed that glucocorticoids induce cytochrome P-450p, a liver microsomal hemoprotein originally isolated from rats treated with the antiglucocorticoid pregnenolone 16 alpha-carbonitrile (PCN), through a mechanism that involves a stereospecific recognition system clearly distinguishable from the classic glucocorticoid receptor (Schuetz, E. G., Wrighton, S. A., Barwick, J. L., and Guzelian, P. S. (1984) J. Biol. Chem. 259, 1999-2012). We now report that digitoxigenin monodigitoxoside UDP-glucuronosyltransferase (DIG UDP glucuronosyltransferase), a liver microsomal enzyme activity induced by PCN in rats, is also inducible, as is P-450p, in primary monolayer cultures of adult rat hepatocytes. DIG UDP-glucuronosyltransferase activity closely resembled reported characteristics of induction of P-450p in its time course of induction, concentration-response relationships, exclusivity of induction by steroids with glucocorticoid properties, unusual rank order of potency of glucocorticoid agonists, unusually high ED50 for induction by glucocorticoids, enhanced induction rather than inhibition by anti-glucocorticoids in the presence of glucocorticoids, and finally, induction by nonsteroidal inducers of P-450p. DIG UDP-glucuronosyltransferase activity was also readily detected in human liver microsomes and was elevated in two patients who had received inducers of P-450p. We conclude that the liver enzymes controlled by the postulated PCN recognition system include not only P-450p but also one or more UDP-glucuronosyltransferases. PMID- 3087973 TI - Characterization of synapsin I binding to small synaptic vesicles. AB - The binding of synapsin I, a synaptic vesicle-associated phosphoprotein, to small synaptic vesicles has been examined. For this study, synapsin I was purified under nondenaturing conditions from rat brain, using the zwitterionic detergent 3 [(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), and characterized. Small synaptic vesicles were purified from rat neocortex by controlled pore glass chromatography as the last purification step, and binding was characterized at an ionic strength equivalent to 40 mM NaCl. After removal of endogenous synapsin I, exogenous dephospho-synapsin I bound with high affinity (Kd, 10 +/- 6 nM) to synaptic vesicles. The binding saturated at 76 +/- 40 micrograms synapsin I/mg of vesicle protein, which corresponded to the amount found endogenously in purified vesicles. Synapsin I binding exhibited a broad pH optimum around pH 7. Other basic proteins, specifically myelin basic protein and histone H2b, did not compete with synapsin I for binding to vesicles. Other membranes purified from rat brain and membranes derived from human erythrocytes did not show the high affinity binding site for synapsin I found in vesicles. The binding of three different forms of phosphosynapsin I to vesicles was investigated. Synapsin I, phosphorylated at sites 2 and 3 by purified calcium/calmodulin-dependent protein kinase II, bound with a 5-fold lower affinity to the vesicles than did dephospho-synapsin I. In contrast, synapsin I, phosphorylated at site 1 by purified catalytic subunit of cAMP-dependent protein kinase, bound with an affinity close to that of dephospho-synapsin I. Synapsin I phosphorylated on all three sites bound to the vesicles with an affinity comparable to that of synapsin I phosphorylated on sites 2 and 3. Under conditions of higher ionic strength (150 mM NaCl equivalent), synapsin I bound with a 5-fold lower affinity to vesicles, and no effect of phosphorylation on binding was observed under these conditions. PMID- 3087974 TI - Association of synapsin I with neuronal cytoskeleton. Identification in cytoskeletal preparations in vitro and immunocytochemical localization in brain of synapsin I. AB - Calmodulin-dependent protein kinase II (CaM kinase II) is associated with microtubule preparations and phosphorylates several endogenous proteins including microtubule-associated protein 2, tubulin, and an 80,000-dalton protein doublet (pp80). We now report that pp80 is identical to synapsin I by all criteria studied including molecular weight, isoelectric point, phosphopeptide mapping of cAMP- and calmodulin-dependent phosphorylated protein, comigration with authentic synapsin I, and sensitivity to digestion with collagenase. Synapsin I and CaM kinase II were found in association with both microtubule preparations and preparations enriched in neurofilaments. Antibodies to synapsin I specifically labeled neurofilaments prepared in vitro. Immunocytochemical studies on rat brain tissue demonstrated synapsin I immunoreactivity specifically associated with the neuronal cytoskeleton as well as synaptic vesicles. The observed synapsin I staining on cytoskeletal elements was considerably diminished or abolished by the inclusion of Triton X-100 in the staining solutions. These results indicate that synapsin I is associated with the cytoskeleton and may be an important link between cytoskeletal elements as well as between the cytoskeleton and membrane. PMID- 3087976 TI - Role of polycationic C-terminal portion in the structure and activity of recombinant human interferon-gamma. AB - Purified recombinant human interferon-gamma, produced in Escherichia coli, was digested with trypsin under mild conditions, resulting in a preparation containing approximately 90% of a Mr = 15,800 protein and 10% of a 14,400 protein. The Mr = 15,800 protein has an intact N terminus and the Mr = 14,400 protein lacks 14 N-terminal residues. Both proteins lack C terminus of approximately 13 residues. This preparation containing the Mr = 15,800 and 14,400 proteins was identical with the intact protein with respect to conformation and dimerization, as analyzed by circular dichroism and gel filtration. However, the antiviral activity of this preparation was 1000-fold lower than that of the intact molecule. Since the majority of this preparation is the Mr = 15,800 protein, these results suggest that the C terminus does not affect the protein conformation and self-association, but greatly alters antiviral activity. PMID- 3087975 TI - Purification and characterization of guanine phosphoribosyltransferase from Giardia lamblia. AB - Giardia lamblia, a flagellated parasitic protozoan and the causative agent of giardiasis, lacks de novo purine biosynthesis and exists on salvage of adenine and guanine by adenine phosphoribosyltransferase and guanine phosphoribosyltransferase. Guanine phosphoribosyltransferase from G. lamblia crude extracts has been purified to apparent homogeneity by Sephacryl S-200 gel filtration followed by C-8-GMP-agarose and 2',3'-GMP-agarose affinity chromatography, resulting in an overall recovery of 77% and a purification of 83,000-fold. The molecular weight of the native enzyme as estimated by gel filtration and isokinetic sucrose gradients was found to be 58,000-63,000, with a subunit molecular weight of approximately 29,000, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mono P chromatofocusing chromatography gives rise to a major activity peak eluting from the column at a pH of 6.75 and two minor activity peaks at pH of 5.3 and 5.2. Hypoxanthine and xanthine can be recognized by the enzyme as substrates but at Km values 20 times higher than that observed with guanine. G. lamblia guanine phosphoribosyltransferase is immunologically distinct from human hypoxanthine guanine phosphoribosyltransferase and Escherichia coli xanthine-guanine phosphoribosyltransferase, and G. lamblia DNA fragments are incapable of hybridizing with mouse neuroblastoma hypoxanthine-guanine phosphoribosyltransferase DNA or E. coli xanthine phosphoribosyltransferase DNA under relatively relaxed conditions. All evidence presented suggests that G. lamblia guanine phosphoribosyltransferase may be qualified as a potential target for antigiardiasis chemotherapy. PMID- 3087977 TI - Identification of a high affinity leukotriene C4-binding protein in rat liver cytosol as glutathione S-transferase. AB - A soluble high affinity binding unit for leukotriene (LT) C4 in the high speed supernatant of rat liver homogenate was characterized at 4 degrees C as having a single type of saturable affinity site with a dissociation constant of 0.77 +/- 0.27 nM (mean +/- S.E., n = 5). The binding activity was identified as the liver cytosolic subunit 1 (Ya) of glutathione S-transferase, commonly known as ligandin, by co-purification with the catalytic activity during DEAE-cellulose column chromatography and 11,12,14,15-tetrahydro-LTC4 (LTC2)-affinity gel column chromatography; resolution into two major bands by sodium dodecyl sulfate polyacrylamide gel electrophoresis of Mr 23,000 and 25,000, of which only the smaller protein was labeled with [3H]LTC4 coupled via a photoaffinity cross linking reagent; and immunodiffusion analysis with rabbit antiserum to glutathione S-transferase which showed a line of identity between the purified LTC4-binding protein and rat liver glutathione S-transferase. The affinity purified binding protein bound 800 pmol of [3H] LTC4/mg of protein and possessed 12 mumol/min/mg of glutathione transferase activity as assayed with 1-chloro-2,4 dinitrobenzene as substrate. The enzyme activity of the cytosolic LTC4-binding protein was inhibited by submicromolar quantities of unlabeled LTC4, and the binding activity for [3H]LTC4 was blocked by the ligandin substrates, hematin and bilirubin. The high affinity interaction between LTC4 and glutathione S transferase suggests that glutathione S-transferase may have a role in LTC4 disposition and that previous studies of LTC4 binding to putative receptors in nonresponsive tissues may require redefinition of the binding unit. PMID- 3087978 TI - Plant acyl-CoA oxidase. Purification, characterization, and monomeric apoprotein. AB - Purified glyoxysomes from cotyledons of germinating cucumber seedlings were used as a source to separate matrix enzymes of the organelle by hydrophobic chromatography. Glyoxysomal acyl-CoA oxidase eluted from the column like hydrophobic proteins and exhibited an Mr of 150,000. An oxidase with identical properties could be prepared in large quantities by a purification procedure starting with crude extracts from cotyledons of 4-day-old etiolated seedlings. The purification procedure included chromatography on phenyl-Sepharose and hydroxylapatite and molecular sieving. 1500-fold purification led to an enzyme of apparent homogeneity characterized by a specific activity of 27 units/mg of protein. Plant acyl-CoA oxidase is a homodimer with a subunit of Mr 72,000. Monospecific antibodies raised in rabbits were used to reveal dissimilarity to the fungal oxidase. The plant enzyme also differed markedly in molecular structure and amino acid composition from the liver peroxisomal enzyme. Glyoxysomal acyl-CoA oxidase acts selectively on fatty acyl-CoAs with 16 or 18 C atoms, cis-9-unsaturated esters with a C16 or C18 acyl moiety being converted with higher rates than saturated or polyunsaturated fatty acyl-CoAs. Besides the enzymatically active organellar form of acyl-CoA oxidase, the monomeric apoprotein was detected when short-term labeling of cotyledons in vivo was performed. The apoprotein (immunoprecipitable by antibodies raised against the glyoxysomal enzyme) did not differ in size from the subunit of the glyoxysomal dimeric enzyme. PMID- 3087979 TI - Molecular characterization of the interferon-induced 15-kDa protein. Molecular cloning and nucleotide and amino acid sequence. AB - We have isolated a cDNA clone for an interferon-induced 15-kDa protein. The cDNA clone was prepared from mRNA isolated from interferon-beta-treated human Daudi cells. The clone of 635 base pairs contains an open reading frame coding for a protein of 145 amino acids, and suggests for the mRNA a 75-base pair 5' untranslated and a 125-base pair 3' untranslated region. Approximately 85% of the amino acid sequence of the 15-kDa protein has been independently obtained from 2 nmol of material using microsequencing technology on the N terminus of the intact protein and on tryptic and chymotryptic peptides. The amino acid sequence of the isolated protein is identical to the amino acid sequence deduced from the cDNA. Northern blot analysis confirmed that the mRNA for the 15-kDa protein is undetectable in untreated cells, but is greatly induced following interferon treatment. PMID- 3087981 TI - Immunologic comparison of the conformations of apolipoprotein B. Investigation of methodologies for the reconstitution of delipidated and denatured apolipoprotein B with nonionic surfactants. AB - Immunologic probes have been used to examine the conformation of apolipoprotein B (apo-B) as it exists within native low density lipoprotein (LDL) after lipid displacement with Triton X-100 and after denaturation with guanidine hydrochloride organic solvent delipidation and reconstitution with Triton X-100. Antigenic expression was assayed in two systems: by using either Triton X-100 or bovine serum albumin to maintain protein solubility. Apo-B delipidated by lipid displacement using Triton X-100 was virtually identical to LDL-apo-B in both systems, as assayed by polyclonal antisera prepared in rabbits against either antigen. Thus the native antigenic sites are preserved, although the displacement of the lipid core of LDL drastically alters the physical properties of the particle. Apo-B delipidated by solvent extraction in guanidine was reconstituted with Triton X-100 by several methods, and the products were examined immunologically. One method yielded a product that resembled apo-B as delipidated with Triton X-100, although full reconstitution could not be achieved. Nevertheless, Triton promoted refolding of apo-B to reform partial native structure as judged immunologically. By using both physical and immunologic methods for assessing structure, it is clearly evident that the perceptions of the conformational states of reconstituted apo-B can be very different, and multiple criteria need to be used to assess lipoprotein reconstitution. PMID- 3087980 TI - Innocuous character of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid and EDTA as metal-ion buffers in studying Ca2+ binding by alpha-lactalbumin. AB - The binding of EGTA and EDTA to alpha-lactalbumin, first demonstrated by Kronman and Bratcher (Kronman, M. J., and Bratcher, S. C. (1983) J. Biol. Chem. 258, 5707 5709) and afterwards regarded as a significant source of error in estimating the binding constant of Ca2+ to the protein, has been investigated by comparison of the thermal unfolding curves of the protein in the absence and presence of the chelators and also by measuring the NMR spectra of the protein, the chelators, and the protein-chelator mixtures. The unfolding curve in the presence of a large excess of each chelator has been found to be identical to that in the absence of chelator, indicating that there is essentially no interaction between the chelators and alpha-lactalbumin. The NMR results have also supported this conclusion, and the innocuous character of these chelators as metal-ion buffers in studying the Ca2+-binding properties of alpha-lactalbumin is demonstrated. In order to re-examine the binding constant for Ca2+ of alpha-lactalbumin without the aid of chelating metal-ion buffers, the thermal unfolding curve of the protein in the presence of 0.1 mM excess Ca2+ but without chelators has been compared with the unfolding curve in the absence of Ca2+ at a constant concentration of Na+ (0.010 or 0.10 M) at pH 7.0. The binding constant of alpha lactalbumin can be calculated from the increment of melting temperature caused by the presence of Ca2+ and from the enthalpy and heat capacity changes in the unfolding. Because Ca2+ binding to the unfolded protein can be neglected under the conditions employed, the binding constant evaluated corresponds to the binding constant to protein that has native structure. The constant obtained is 3 5 X 10(9) M-1 after corrections for binding of Na+ to the protein and for ionic strength, and this shows excellent agreement with the corresponding value previously estimated (2.9 +/- 1.0 X 10(9) M-1), although the latter value was obtained in the presence of EDTA. The apparent Ca2+-binding constant that has been discussed in most previous studies, without taking account of the folding unfolding equilibrium associated with the binding process, also depends on the concentration of monovalent cations such as Na+, and the present results lead to values of 1.5 X 10(8) and 8.7 X 10(6) M-1 at 0.01 and 0.1 M Na+, respectively. PMID- 3087983 TI - Monoclonal antibodies against human erythrocyte band 3 protein. Localization of proteolytic cleavage sites and stilbenedisulfonate-binding lysine residues. AB - Monoclonal antibodies against the membrane domain of human red blood cell band 3 protein have been prepared and used in topographical studies of the arrangement of the polypeptide in the membrane. One of the antibodies binds to a site near the N terminus of the membrane domain; another binds to a site near the C terminus. The latter has been used to localize a site of intracellular trypsin digestion. The cleavage site, in human band 3, corresponds to Lys-761 in mouse band 3; the site is 168 residues from the C terminus of the protein. This is the first intracellular site in the membrane domain (other than the N terminus) that has been localized in the primary structure. The antibody that binds to the N terminal portion of the membrane domain has been used to identify a new S cyanylation cleavage site about 7,000 daltons from the C terminus. Proteolysis/cross-linking experiments with the stilbenedisulfonate derivative H2DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonate) reveal that one end of the H2DIDS reacts covalently with a lysine residue that is between about 70 and 168 residues from the C terminus of band 3. In addition to placing restrictions on the location of the H2DIDS-binding lysine, these studies provide direct evidence that the C-terminal 28,000-dalton papain fragment crosses the membrane at least three times. With previous data on the remainder of the membrane domain, there is now direct evidence that the band 3 polypeptide crosses the membrane at least eight times. PMID- 3087982 TI - Site-specific mutagenesis of cysteine 148 to serine in the lac permease of Escherichia coli. AB - Oligonucleotide-directed, site-specific mutagenesis has been utilized to modify the lac Y gene of Escherichia coli such that Cys148 in the lac permease is converted to Ser. A mutagenesis protocol is used that significantly improves the efficiency of mutant recovery by in vitro methylation of closed-circular heteroduplex DNA containing the mutation, followed by nicking with HindIII in the presence of ethidium bromide and heat denaturation prior to transfection. In contrast to Gly148 permease (Trumble, W.R., Viitanen, P.V., Sarkar, H.K., Poonian, M.S., and Kaback, H. R. (1984) Biochem. Biophys. Res. Commun. 119, 860 867), permease containing Ser at position 148 catalyzes active lactose transport at a rate comparable to wild-type permease. Like Gly148 permease, however, transport activity is less sensitive to inactivation by N-ethylmaleimide, and galactosyl-1-thio-beta-D-galactopyranoside affords no protection against inactivation. The observations provide strong support for the contention that Cys148 is obligatory for substrate protection against inactivation by sulfhydryl reagents, but does not play an essential role in lactose:H+ symport. PMID- 3087984 TI - Development of muscarinic cholinergic inhibition of adenylate cyclase in embryonic chick heart. Its relationship to changes in the inhibitory guanine nucleotide regulatory protein. AB - Parasympathetic and sympathetic innervation of the embryonic chick heart proceed non-coordinately. beta-Adrenergic agonists mediate an increase in beating rate in embryonic chick heart prior to ingrowth of the vagus nerve (Culver, N. G., and Fishman, D. A. (1977) Am. J. Physiol. 232, R116-R123) while muscarinic agonists exert relatively little effect on beating rate in hearts 2-4 days in ovo (Papanno, A. J. (1979) Pharmacol. Rev. 29, 3-33). Studies of developmental changes in the ability of muscarinic agonists to inhibit adenylate cyclase activity and their relationship to the development of a physiologic response of the embryonic chick heart to muscarinic stimulation have been inconclusive. In the current studies the ability of isoproterenol to stimulate adenylate cyclase activity did not change during development. Maximum stimulation above basal was 760 pmol of cAMP/10 min/mg of proterin with an IC50 of 1.5 X 10(-6) M for isoproterenol in homogenates of hearts 2 1/2, 3 1/2, and 10 days in ovo and 3 days posthatching. However, inhibition of isoproterenol-stimulated adenylate cyclase activity by carbamylcholine increased from 7.6% with a IC50 for carbamylcholine of 16 +/- 5.0 microM at day 2 1/2 in ovo to 29% with an IC50 of 0.4 +/- 0.1 microM at day 10 in ovo and to 43% with a IC50 of 0.6 +/- 0.1 microM at 3 days posthatching. Since previous data had demonstrated the presence of muscarinic receptors as early as 2 1/2 days in ovo (Galper, J. B., Klein, W., and Catterall, W. A. (1977) J. Biol. Chem. 252, 8692-8699), studies of developmental changes in guanine nucleotide-coupling proteins were carried out to determine whether early in development muscarinic receptors were uncoupled from a physiologic response. Studies of pertussis toxin-catalyzed ADP-ribosylation of homogenates of embryonic chick heart with [32P]NAD demonstrated the presence of two ADP-ribosylated proteins at 39,000 and 41,000 kDa, respectively. Both ADP ribosylation and immunoblotting of homogenates with an antibody to the 39-kDa guanine nucleotide-binding protein in bovine brain demonstrated that the 39-kDa alpha protein increased 1.8-fold between days 2 1/2 and 3 1/2 in ovo and another 1.8-fold from day 3 1/2 to 10 in ovo in parallel with the increase in the extent of muscarinic inhibition of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3087985 TI - Immune interferon suppresses levels of procollagen mRNA and type II collagen synthesis in cultured human articular and costal chondrocytes. AB - Cultured human articular and costal chondrocytes were used as a model system to examine the effects of recombinant gamma-interferon (IFN-gamma) on synthesis of procollagens, the steady state levels of types I and II procollagen mRNAs, and the expression of major histocompatibility complex class II (Ia-like) antigens on the cell surface. Adult articular chondrocytes synthesized mainly type II collagen during weeks 1-3 of primary culture, whereas types I and III collagens were also produced after longer incubation and predominated after the first subculture. Juvenile costal chondrocytes synthesized no detectable alpha 2(I) collagen chains until after week 1 of primary culture; type II collagen was the predominant species even after weeks of culture. The relative amounts of types I and II collagens synthesized were reflected in the levels of alpha 1(I), alpha 2(I), and alpha 1(II) procollagen mRNAs. In articular chondrocytes, the levels of alpha 1(I) procollagen mRNA were disproportionately low (alpha 1(I)/alpha 2(I) less than 1.0) compared with costal chondrocytes (alpha 1 (I)/alpha 2(I) approximately 2). Recombinant IFN-gamma (0.1-100 units/ml) inhibited synthesis of type II as well as types I and III collagens associated with suppression of the levels of alpha 1(I), alpha 2(I), and alpha 1(II) procollagen mRNAs. IFN-gamma suppressed the levels of alpha 1(I) and alpha 1(II) procollagen mRNAs to a greater extent than alpha 2(I) procollagen mRNA in articular but not in costal chondrocytes. Human leukocyte interferon (IFN-alpha) at 1000 units/ml suppressed collagen synthesis and procollagen mRNA levels to a similar extent as IFN-gamma at 1.0 unit/ml. In addition, IFN-gamma but not IFN-alpha induced the expression of HLA-DR antigens on intact cells. The lymphokine IFN-gamma could, therefore, have a role in suppressing cartilage matrix synthesis in vivo under conditions in which the chondrocytes are in proximity to T lymphocytes and their products. PMID- 3087986 TI - Identification of the interleukin-3 receptor using an iodinatable, cleavable, photoreactive cross-linking agent. AB - Murine interleukin-3 (mIL-3) is a lymphokine that stimulates the proliferation and differentiation of both pluripotent hemopoietic stem cells and their committed progeny. However, very little is known about the mechanism by which this growth factor elicits its effects on responsive cell populations. To gain insight into early events following mIL-3 receptor interaction, we initiated studies to isolate the receptor and study its properties. In this report, we demonstrate the use of a new iodinatable, cleavable, photoreactive cross-linking agent, sulfosuccinimidyl 2-(p-azidosalicylamido)-1,3'-dithiopropionate to identify the mIL-3 receptor. These studies reveal the mIL-3 receptor to be a single polypeptide chain with a molecular weight of 67 kDa and an isoelectric point of approximately 6.2. PMID- 3087987 TI - A possible role for protein phosphorylation in the activation of the respiratory burst in human neutrophils. Evidence from studies with cells from patients with chronic granulomatous disease. AB - Two-dimensional gel electrophoresis was used to study protein phosphorylation in granules, membranes, and soluble fractions from human neutrophils that had been loaded with 32Pi. In resting cells, label was incorporated primarily into proteins of the membranes and the soluble supernatant; little appeared in the granules. Activation of 32P-loaded neutrophils resulted in an increase in the 32P content of a small number of membrane and soluble proteins without a change in the labeling of the granule fraction. The identity of the proteins affected by activation depended on the activating agent used; all of the activating agents, however, caused an increase in the labeling of a group of approximately 48-kDa proteins that appeared to be distributed between the membranes and the soluble supernatant. To investigate the role of phosphorylation in the activation of the respiratory burst oxidase, the incorporation of 32P into phosphoproteins was studied in neutrophils from patients with chronic granulomatous disease. When these cells were exposed to phorbol myristate acetate, one of the agents used for the activation of normal neutrophils, the 48-kDa proteins in the membranes and supernatants failed to take up additional 32P. Phosphorylation patterns in normal neutrophils activated under nitrogen were similar to the patterns seen with cells activated in air, suggesting that the differences in phosphorylation between normal and chronic granulomatous disease neutrophils did not represent secondary effects of the oxidants produced by the normal cells, but reflected primary biochemical differences between the normal and the defective phagocytes. We postulate from these results that the uptake of phosphate by the 48-kDa protein group may be involved in the activation of the respiratory burst oxidase. PMID- 3087988 TI - Glycosaminoglycan production by bovine aortic endothelial cells cultured in sulfate-depleted medium. AB - Bovine aortic endothelial cells were cultured in medium containing [3H]glucosamine and concentrations of [35S]sulfate ranging from 0.01 to 0.31 mM. While the amount of [3H]hexosamine incorporated into chondroitin sulfate and heparan sulfate was constant, decreasing concentrations of sulfate resulted in lower [35S]sulfate incorporation. Sulfate concentrations greater than 0.11 mM were required for maximal [35S]sulfate incorporation. Chondroitin sulfate was particularly affected so that the sulfate to hexosamine ratio in [3H]chondroitin [35S]sulfate dropped considerably more than the sulfate to hexosamine ratio in [3H] heparan [35S]sulfate. Sulfate concentration had no effect on the ratio of chondroitin 4-sulfate to chondroitin 6-sulfate. The ratios of sulfate to hexosamine in cell-associated glycosaminoglycans were essentially identical with the ratios in media glycosaminoglycans at all sulfate concentrations. DEAE cellulose chromatography confirmed that sulfation of chondroitin sulfate was particularly sensitive to low sulfate concentrations. While cells incubated in medium containing 0.31 mM sulfate produced chondroitin sulfate which eluted later than heparan sulfate, cells incubated in medium containing less than 0.04 mM sulfate produced chondroitin sulfate which eluted before heparan sulfate and near hyaluronic acid, indicating that many chains were essentially unsulfated. At intermediate concentrations of sulfate, chondroitin sulfate was found in very broad elution patterns suggesting that most did not fit an "all or nothing" mechanism. Heparan sulfate produced at low concentrations of sulfate eluted with narrower elution patterns than chondroitin sulfate, and there was no indication of any "all or nothing" sulfation. PMID- 3087989 TI - A novel mechanism of diglyceride formation. 12-O-tetradecanoylphorbol-13-acetate stimulates the cyclic breakdown and resynthesis of phosphatidylcholine. AB - 12-O-Tetradecanoylphorbol-13-acetate (TPA) treatment of Madin-Darby canine kidney cells resulted in an increased incorporation of 32Pi and [methyl-3H]choline into choline-containing phosphoglycerides (PC). In pulse-chase experiments, TPA treatment caused an increased release of [methyl-3H]choline from the PC fraction of prelabeled cells. When cells were prelabeled with [3H]arachidonic acid and [14C]palmitic acid, TPA treatment resulted in an increased synthesis of 14C, 3H diglycerides. Further studies were done to determine the relationship between PC breakdown and diglyceride synthesis. Cells were preincubated with ether-linked 1 O-[3H]hexadecyl-2-lyso-sn-glycero-3-phosphocholine which was acylated to form 1-O [3H]hexadecyl-2-acyl-sn-glycero-3-phosphocholine. Subsequent treatment of these cells with TPA resulted in an increased synthesis of 1-O-[3H]hexadecyl-2-acyl-sn glycerol compared to cells not stimulated with TPA. These findings demonstrate that TPA stimulates PC turnover in Madin-Darby canine kidney cells and provide evidence for a novel mechanism of diglyceride formation. PMID- 3087990 TI - Isolation and biosynthesis of 20-hydroxyprostaglandins E1 and E2 in ram seminal fluid. AB - Ram semen was found to contain 20-hydroxyprostaglandin E1 and 20 hydroxyprostaglandin E2. The relative amounts of the two compounds were almost equal, although ram semen contained at least 10 times more prostaglandin E1 than prostaglandin E2. The accessory genital glands of the ram were analyzed for their capacity to metabolize [14C]arachidonic acid to prostaglandins. Biosynthesis of prostaglandins was only found in microsomes of the mucosa of the ampulla of vas deferens and in microsomes of the vesicular glands. Ram vesicular glands and the ampulla of vas deferens were also found to contain the two 20-hydroxylated E prostaglandins. Microsomes of ram vesicular glands and NADPH metabolized exogenous prostaglandin E2 to 20-hydroxyprostaglandin E2 albeit in low yields. Prostaglandin E2 appeared to be a better substrate than prostaglandin E1. Microsomes of human seminal vesicles and NADPH metabolized exogenous prostaglandin E2 to 19-hydroxyprostaglandin E2. The results show that 19- and 20 hydroxylation of prostaglandins occurs in human and ram seminal vesicles, respectively, and possibly also in the ampulla of vas deferens of the ram. The ram and human enzymes specifically hydroxylated the terminal and the penultimate carbon of prostaglandin E2, respectively. PMID- 3087991 TI - Spectroscopic characterization of the number and type of iron-sulfur clusters in NADH:ubiquinone oxidoreductase. AB - The number and type of iron-sulfur clusters present in the NADH dehydrogenase of the mammalian respiratory chain were studied by a combination of low temperature magnetic circular dichroism (MCD) and quantitative electron paramagnetic resonance spectroscopies. MCD was used with the high molecular weight, soluble enzyme, and EPR was used with both the purified enzyme and Complex I (NADH:ubiquinone oxidoreductase). The results of the EPR experiments of the two types of preparations agreed with each other, as well as with the data in the literature for various types of membrane-bound preparations. The two methods gave concordant results showing the presence of one binuclear and of three tetranuclear NADH-reducible iron-sulfur clusters. Earlier studies using the cluster extrusion technique indicated a higher ratio of binuclear to tetranuclear clusters which may be explained by cluster interconversion during the extrusion process. PMID- 3087993 TI - Plasminogen activators and their inhibitors in a human mammary cell line (HBL 100). Modulation by glucocorticoids. AB - Culture of human mammary HBL-100 cells in the presence of dexamethasone, a synthetic glucocorticoid, resulted in opposite effects on the production of the two plasminogen activators (PAs): a decrease in urokinase-type PA (u-PA) and a concomitant increase in tissue-type PA (t-PA). Two PA-specific inhibitors, one related to that produced by bovine aortic endothelial cells, and the other related to that isolated from human placenta, were also produced by these cells; dexamethasone did not affect the production of either of these inhibitors. The glucocorticoid effects observed on PA enzymatic activities were associated with changes in PA mRNA levels. Experiments using inhibitors of RNA and protein synthesis suggested that the glucocorticoid-induced decrease in u-PA mRNA was a secondary event, requiring synthesis of new regulatory proteins; in contrast, the increase in t-PA mRNA appeared to be a direct effect on t-PA gene expression. PMID- 3087994 TI - Bovine coagulation factor V visualized with electron microscopy. Ultrastructure of the isolated activated forms and of the activation fragments. AB - Single chain bovine factor V (Mr = 330,000) was isolated and visualized by means of high resolution transmission electron microscopy of negatively stained samples. Both factor Va, activated by thrombin or by the factor V activator from Russell's viper venom, and the isolated fragments, D (Mr = 105,000), C1 (Mr = 150,000), and F1F2 (Mr = 72,000), were studied. Single chain factor V appeared as a multidomain structure with three globular domains of similar size (diameter approximately 80 A), and oriented around a somewhat larger central domain (diameter approximately 140 A). The distance between the center of the molecule and the center of each of the peripheral domains was 120 A and the maximum length of factor V was 300 A. The structure was essentially identical with that recently shown for human single chain factor V (Dahlback, B. (1985) J. Biol. Chem. 260, 1347-1349). Isolated thrombin-activated factor Va (containing fragments D and F1F2) was composed of two domains of similar size, each of which was approximately 80 A in diameter and corresponded in size and shape to the peripheral domains seen in intact factor V. The isolated activation fragment C1 appeared as an irregular structure with an approximate diameter of 140 A and corresponded in size and shape to the larger central domain in intact factor V. The activator from Russell's viper venom only cleaves the bond(s) between C1 and F1F2, which results in two fragments, a larger fragment (Mr = 220,000) bearing the D, E, and C1 region and a smaller one corresponding to the F1F2 fragment. The venom-activated factor Va in the electron microscope demonstrated a multidomain structure similar in size and shape to that obtained with intact factor V. A model for factor V and the molecular events involved in activation is proposed. PMID- 3087992 TI - Different calcium dependence of the capping and cutting activities of villin. AB - The concentration of ionized calcium required for the capping of barbed filament ends by villin is about 4 orders of magnitude lower than that required for the cutting activity of villin. Capping was 50% complete at about 10-30 nM Ca2+, a level expected in resting cells, whereas the cutting rate was half-maximal at about 200 microM, making it possible to completely separate filament capping from filament cutting. Analysis of capping in terms of coupled equilibria between calcium binding to villin and calcium-villin binding to the barbed ends of actin filaments gives a value of 10(16)-10(17) M-2 for the product of the two binding constants. By comparison the binding constant reported for the rapidly exchanging calcium sites on villin is 2 X 10(5) M-1 and that for binding of calcium saturated villin to barbed ends has a minimum value of 10(11) M-1 giving a product of 2 X 10(16) M-1. The close similarity of the two sets of values suggests that capping is regulated by the rapidly exchanging calcium sites on villin. In terms of coupled equilibria the calcium requirement for filament capping decreases with increasing concentrations of free villin. The scant information on the mechanism of cutting allows only an estimate of the maximal value for the calcium-binding constant of the site regulating cutting which is about 2-5 X 10(3) M-1. Cutting is followed by rapid capping of the newly released barbed ends. PMID- 3087995 TI - The metabolic response to injury: mechanisms and clinical implications. PMID- 3087997 TI - Concanavalin A inhibits oral regeneration in Stentor coeruleus through a mechanism involving binding to the cell surface. AB - Concanavalin A (Con A) has been shown to induce delays in oral regeneration in the ciliate Stentor coeruleus. Associated with the delayed oral regeneration is a shedding of the cell's extracellular pellicle with the loss of some pigment granules. It is shown that the delays in oral regeneration are not the result of the pigment shedding. The delays are localized in the earliest stages of oral regeneration prior to stage 4. The delays caused by Con A are completely reversible by the addition of 2 mg/ml alpha-D-methyl mannoside either at the time of Con A exposure or 5 min later. Con A clearly binds to the cell surface as shown by the binding of FITC-Con A and its reversal by alpha-methyl mannoside. Crosslinking of Con A receptor molecules may be responsible for the effects of Con A since succinyl Con A, which does not crosslink these receptors, has no effect on oral regeneration even at double the Con A concentration. Calcium ions are also implicated in the action of Con A because an excess of extracellular calcium (10 mM) completely eliminates the Con A delays when added simultaneously with Con A. Examination of the minimum extracellular calcium concentration required for this effect showed that 2 mM calcium can reverse most of the delays but that 5 mM is necessary to completely reverse the delays caused by Con A. If the addition of calcium is delayed for various times after Con A addition, the extracellular calcium is progressively less effective in reversing the Con A delays. PMID- 3087998 TI - Age dependency of the metabolic conversion of polyamines into amino acids in IMR 90 human embryonic lung diploid fibroblasts. AB - When radioactive polyamines (putrescine or spermidine) were incubated with mammalian cells in tissue culture, the radioactivity was incorporated into cellular proteins via two different metabolic pathways; one is metabolic labeling of an 18,000-dalton protein via hypusine formation, and the other is general protein synthesis employing radioactive amino acids derived from biodegradation of polyamines via GABA shunt and Krebs cycle. Aminoguanidine, a potent inhibitor of diamine oxidase, blocked the metabolic conversion of polyamines to amino acids but had no effect on the metabolic labeling of the 18,000-dalton protein. We have investigated these two polyamine-associated biochemical events in IMR-90 human diploid fibroblasts as a function of their population doubling level (PDL). We found that (1) the metabolic labeling of the 18,000-dalton protein was about two fold greater in young cells (PDL = 22) than that in old cells (PDL = 48), and (2) the metabolic labeling of other cellular proteins, employing amino acids derived from putrescine via polyamine catabolic pathway, was more than six-fold greater in the old cells (PDL = 48) than in the young cells (PDL = 22). Since the rate of protein synthesis was about 1.4-fold higher in the young cells as compared to the old cells, our data indicated that the activity of catabolic conversion of putrescine (or spermidine) to amino acids in old IMR-90 cells was about eight fold greater than that in young cells. This remarkable increase of polyamine catabolism and the slight decrease of metabolic labeling of the 18,000-dalton protein were also observed in cell strains derived from patients with premature aging disease. PMID- 3087996 TI - Characterization of secretory protein translocation: ribosome-membrane interaction in endoplasmic reticulum. AB - Secretory proteins are synthesized on ribosomes bound to the membrane of the endoplasmic reticulum (ER). After the selection of polysomes synthesizing secretory proteins and their direction to the membrane of the ER via signal recognition particle (SRP) and docking protein respectively, the polysomes become bound to the ER membrane via an unknown, protein-mediated mechanism. To identify proteins involved in protein translocation, beyond the (SRP-docking protein mediated) recognition step, controlled proteolysis was used to functionally inactivate rough microsomes that had previously been depleted of docking protein. As the membranes were treated with increasing levels of protease, they lost their ability to be functionally reconstituted with the active cytoplasmic fragment of docking protein (DPf). This functional inactivation did not correlate with a loss of either signal peptidase activity, nor with the ability of the DPf to reassociate with the membrane. It did correlate, however, with a loss of the ability of the microsomes to bind ribosomes. Ribophorins are putative ribosome binding proteins. Immunoblots developed with monoclonal antibodies against canine ribophorins I and II demonstrated that no correlation exists between the protease induced inability to bind ribosomes and the integrity of the ribophorins. Ribophorin I was 85% resistant and ribophorin II 100% resistant to the levels of protease needed to totally eliminate ribosome binding. Moreover, no direct association was found between ribophorins and ribosomes; upon detergent solubilization at low salt concentrations, ribophorins could be sedimented in the presence or absence of ribosomes. Finally, the alkylating agent N-ethylmaleimide was shown to be capable of inhibiting translocation (beyond the SRP-docking protein-mediated recognition step), but had no affect on the ability of ribosomes to bind to ER membranes. We conclude that potentially two additional proteinaceous components, as yet unidentified, are involved in protein translocation. One is protease sensitive and possibly involved in ribosome binding, the other is N-ethylmaleimide sensitive and of unknown function. PMID- 3087999 TI - Effects of bacterial lipopolysaccharide on protein synthesis in murine peritoneal macrophages: relationship to activation for macrophage tumoricidal function. AB - Early biochemical events in the response of murine peritoneal macrophages to bacterial lipopolysaccharide (LPS) have been examined (i.e., 0-4 hr after initiation of treatment). At concentrations of 10 ng/ml or less, LPS stimulated the new or enhanced synthesis of a series of at least six polypeptides of 85, 80, 75, 65, 57, and 38 kD. This effect was dependent upon the lipid A moiety of LPS as lipid A itself could induce the changes and the effect of LPS could be blocked by inclusion of polymixin B sulfate in the culture medium. The effect was specific for LPS in that other endotoxin-free agents known to alter macrophage physiology could not produce the same changes. The time course of LPS stimulation of macrophage protein synthesis was remarkable in that the synthesis of all six proteins was transient even in the continued presence of LPS, being first detected approximately 1 hr after exposure and no longer apparent by 8-10 hr after treatment was initiated. Furthermore, both pulse-chase and cumulative radiolabeling studies indicated that at least two of the proteins (85 and 38 kD) were short-lived and did not accumulate in LPS-treated cells, suggesting the possibility that they participate in a regulatory rather than a functional role. Macrophage tumoricidal activation involves cooperation in response to two independent signals; interferon gamma and LPS. Pretreatment of macrophages with interferon gamma increased the sensitivity of macrophages to LPS-stimulated protein synthesis by one to two orders of magnitude documenting such cooperativity in molecular terms. The LPS-induced stimulation of specific protein synthesis could be reproduced by treatment of macrophages with heat killed Listeria monocytogenes, a gram-positive, endotoxin-negative bacterial stain which has been shown to substitute effectively for LPS in macrophage tumoricidal activation. Furthermore, reversible inhibition (i.e., treatment with cycloheximide) of protein synthesis during LPS treatment abrogated the acquisition of tumoricidal function. These results identify an early biochemical response to LPS which may be a necessary component of the intracellular transduction of signals which regulate macrophage functional development. PMID- 3088000 TI - Cell proliferation in Allium cepa L. meristems under 8-hydroxyquinoline, a chelating agent that affects DNA and RNA polymerases. AB - 8-Hydroxyquinoline (HQ) chelates Mg2+ and Mn2+ and, secondarily, affects the activities of DNA and RNA polymerases. The in vivo effect of HQ has been estimated in Allium cepa L. meristems growing under new growth kinetics in the presence of this agent. HQ (at both 5 X 10(-5) M and 10(-4) M) depressed incorporation of [3H]uridine much more effectively than that of [3H]-thymidine. Cycle kinetics in meristems behaved as if they were independent of the rates of synthesis or accumulation of RNA since, under HQ, cycle time was only moderately modified and the new cycle kinetics achieved could be explained by the new rates of [3H]thymidine incorporation. Lengthened S periods were partially compensated for by shortened G2 phases, suggesting that, in these cells, both the growth cycle and its coupling with the DNA-division cycle were not disturbed by a decreased amount of RNA. Finally, the nucleolar cycle during mitosis, but not the interphase nucleolus, was modified under the new rates of RNA synthesis. PMID- 3088001 TI - Distribution of chromomeres as a basis of chromosomal coiling. AB - Periodicity in the distribution of prominent bands was analysed from the light and electron microscopic maps of salivary gland chromosomes of Drosophila melanogaster. The data obtained indicate that a similar distribution of prominent chromosomes in an individual interphase chromatid results in a unilateral accumulation of chromatin at the chromonema stage, if the helical axis of chromonema consists of approximately 5-9 interchromomere + chromomere units per turn. Orientation of the largest chromomeres mainly on one lateral half and the smallest chromomeres mainly on the opposite lateral half of the chromonema apparently bends it to form the chromosomal 'macro' coil. Thus the increase in DNA content in the chromomeric loops located at specific intervals along the chromatids may have an important role in the evolution of coiling hierarchy in the eukaryotic chromosomes. PMID- 3088002 TI - Freeze-fracture analysis of thylakoid membranes and photosystem I and II enriched fractions from Phormidium laminosum. AB - Thylakoid membranes of the thermophilic cyanobacterium Phormidium laminosum have been fractionated into photosystem II and photosystem I particles. These fractions have been characterized by their partial electron transport activities, and biochemical and spectral properties. Exoplasmic fracture face and protoplasmic fracture face particles in the unfractionated thylakoid membranes were shown to correspond in size to particles in freeze-fractured photosystem II and photosystem I fractions, respectively. Differences between the histograms of the thylakoid membrane protoplasmic fracture face particles and the isolated photosystem I particles suggest that in addition to photosystem I complexes some of the particles on the thylakoid protoplasmic fracture face may be related to cytochrome b/f complexes, the hydrophobic component of the coupling factor, or respiratory complexes. PMID- 3088003 TI - Fulminant hepatic failure six weeks postpartum. PMID- 3088004 TI - Complications of urinary tract infections. PMID- 3088005 TI - Differential diagnosis of psychiatric disorders in old age. PMID- 3088006 TI - Medical malpractice: can peer review be prophylactic? PMID- 3088007 TI - Adult immunization: protocols and problems. PMID- 3088008 TI - Paroxysms, obtundation in a healthy toddler. PMID- 3088009 TI - Medical and surgical use of prophylactic antibiotics. PMID- 3088010 TI - Fatigue, weight loss, and a large hilar mass. PMID- 3088011 TI - Thomas Sydenham: 'The English Hippocrates'. PMID- 3088012 TI - Traumatic neuralgias. PMID- 3088013 TI - The use of flavor to enhance efficacy of reducing diets. PMID- 3088014 TI - A picture is worth a thousand words. PMID- 3088015 TI - Distortion of cell functions by noncytotoxic viruses. PMID- 3088016 TI - Acute chest pain: emergency room evaluation. PMID- 3088017 TI - Oxygen: toxicity and tolerance. PMID- 3088018 TI - Purification of flavin mononucleotide-dependent and flavin-adenine dinucleotide dependent reduced nicotinamide-adenine dinucleotide phosphate-cytochrome P-450 reductase by high-performance liquid chromatography on hydroxyapatite. PMID- 3088020 TI - Complete androgen insensitivity syndrome characterized by increased concentration of a normal androgen receptor in genital skin fibroblasts. AB - Two siblings with the classical phenotype of complete androgen insensitivity syndrome (CAIS) and increased total cellular androgen receptor concentrations in genital skin fibroblasts (GSF) are described. Testosterone biosynthesis was normal, and there was no evidence of 5 alpha-reductase deficiency. Specific binding of [3H]dihydrotestosterone ([3H]DHT) in GSF was 7 SD above the mean value in normal fibroblast strains [maximum binding, 775 +/- 185 X 10(-18) mol/micrograms DNA (mean +/- SD)]. Binding at 40 C was stable, and the androgen receptor complex dissociated at a normal rate (t1/2, 85 min). The androgen receptor complex from GSF cytosol sedimented at 5-6S on sucrose density gradients in the presence of sodium molybdate. In a whole cell binding assay, the percentage of [3H]DHT that bound to a crude nuclear pellet was 60%. Preincubation of GSF with 2 nM [3H]DHT for 20 h before the standard 1-h whole cell binding assay produced a further augmentation in elevated total cellular androgen receptor concentrations. A new variant of CAIS is described which is characterized by an increased concentration of androgen receptors that appear to be quantitatively and qualitatively normal. Augmentation of the receptor by androgen suggests that the gene coding for the androgen receptor is intact and does not account for the androgen insensitivity. PMID- 3088019 TI - Single subcutaneous doses of a luteinizing hormone-releasing hormone antagonist suppress serum gonadotropin and testosterone levels in normal men. AB - The ability of single doses of a LHRH antagonist [Ac-delta 3Pro1, 4F-D-Phe2, D Trp3,6]LHRH (4F-antagonist) to suppress serum gonadotropin and testosterone levels was studied in six normal men. The 4F-antagonist was given sc at four doses: 40, 80, 160, and 320 micrograms/kg body weight. Serum immunoreactive LH, FSH, and testosterone and bioactive LH were measured at intervals for the subsequent 18 h. Serum LH decreased rapidly by (mean +/- SE) 39.7 +/- 2.7%, 41.6 +/- 5.4%, 45.5 +/- 4.7%, and 45.3 +/- 5.4% after each of the four doses. The mean number of LH pulses and their amplitude decreased after each dose and remained suppressed for at least 6 h. After each of the four doses, mean serum FSH levels decreased by 20.0 +/- 4.1%, 33.8 +/- 6.8%, 25.8 +/- 3.6%, and 33.3 +/- 5.7%, and mean serum testosterone levels decreased by 47.7 +/- 7.3%, 55.6 +/- 10.5%, 58.2 +/- 10.8%, and 76.0 +/- 6.0%. Serum testosterone remained low for at least 18 h after the two higher doses. LH bioactivity and the ratio of bioactive LH to immunoreactive LH decreased in all subjects, especially after higher doses of the 4F-antagonist. No side effects or adverse reactions occurred after 4F-antagonist administration, and toxicology studies were negative. These results demonstrate that a single sc injection of this potent LHRH antagonist inhibits the pituitary gonadal axis in normal men. PMID- 3088021 TI - Thyrotropin secretion in thyrotoxic and thyroxine-treated patients: assessment by a sensitive immunoenzymometric assay. AB - A new TSH immunoenzymometric assay was found to be capable of discriminating between the serum TSH values of normal subjects [2.28 +/- 1.02 (+/-SD); range, 0.6-6.5 microU/ml] and those of clinically euthyroid, antithyroid drug-treated (n = 22) or clinically thyrotoxic (n = 34) patients. While a wide spectrum of basal TSH values was found in the antithyroid drug group [ranging from undetectable (less than 0.05 microU/ml: 57%) to 17.9 microU/ml], all clinically thyrotoxic patients had undetectable values. In 33 patients receiving chronic oral T4 therapy for treatment of goiter (n = 15) or thyroid cancer (n = 18), 48% (6 of 33) had undetectable basal TSH levels and no TSH response to TRH stimulation. Detectable TSH levels were found in 42% (14 of 33), and TRH responsiveness was found in 52% (17 of 33). The TSH response to TRH stimulation was less than 2.0 microU/ml in 7 patients. Serum free T4 index, free T3 index, and free T4 levels and oral T4 dosage were inferior predictors of TRH responsiveness compared to the basal TSH value. No patient receiving more than 0.2 mg T4 daily or having a free T4 index above 18, a free T3 index above 205 or a free T4 level above 3.0 ng/dl had a TSH response to TRH. Seventy-six percent (16 of 21) of the patients, when reevaluated 1-6 weeks after increased oral T4 dosage, had a significant reduction in their serum thyroglobulin level. This was true of both patients with initially detectable (11 of 14) as well as undetectable (5 of 7) basal serum TSH levels. These findings support the concept that subnormal and, for that matter, as yet undetectable levels of circulating TSH may exert stimulatory effects on thyroid tissue. PMID- 3088022 TI - A new inherited variant of the 3 beta-hydroxysteroid dehydrogenase-isomerase deficiency syndrome: evidence for the existence of two isoenzymes. AB - The clinical and endocrine features of a unique form of adrenal insufficiency secondary to an inherited deficiency of 3 beta-hydroxysteroid dehydrogenase isomerase (3-HSD) were studied. The propositus was a 19-yr-old man with a history of repeated episodes of acute adrenal crisis. Family study disclosed that a 6-yr old female sibling also was affected, and a third sibling had died during the course of an adrenal crisis. The diagnosis of adrenal insufficiency was established on the basis of extremely low serum cortisol levels and urinary 17 hydroxycorticosteroid excretion with concomitantly elevated serum ACTH levels and lack of cortisol response to ACTH administration. Impairment of C-21 steroid 3 HSD activity was strongly suggested by persistency elevated serum 17 hydroxypregnenolone to 17-hydroxyprogesterone and pregnenolone to progesterone ratios, their significant increase after ACTH administration, and their return to normal during cortisol therapy in both patients. Nevertheless, the serum dehydroepiandrosterone to androstenedione ratio, both basally and after ACTH and/or hCG stimulation, was normal. These findings coupled with the normal phenotypic development and onset of puberty in the two patients indicated intact C-19 steroid 3-HSD activity. The overall results indicate an inherited impairment of 3-HSD activity confined only to C-21 steroid substrates and, thus, suggest the existence of at least two 3-HSD isoenzymes under independent genetic regulation. PMID- 3088023 TI - Effect of cholinergic muscarinic receptor blockade on human growth hormone (GH) releasing hormone-(1-44)-induced GH secretion in acromegaly and type I diabetes mellitus. AB - In 10 patients with type I diabetes mellitus, 9 acromegalic patients, and 8 normal subjects, serum GH levels after an iv injection of 1 microgram/kg BW human GH-releasing hormone-(1-44) (GHRH) with and without cholinergic muscarinic receptor blockade (1 mg atropine, im, 15 min before GHRH) were measured. The GH increase after GHRH treatment in type I diabetic patients did not differ significantly from that in normal subjects. Pretreatment with atropine almost completely blocked the GH response to GHRH in patients with type I diabetes and normal subjects, but did not suppress the GH response to GHRH in acromegalic patients. These data indicate that cholinergic muscarinic receptors modulate GH secretion in normal man as well as in patients with type I diabetes mellitus, whereas acromegalic patients have a defect of cholinergic control of GH secretion. PMID- 3088024 TI - Regulation of growth hormone and somatomedin-C secretion in postmenopausal women: effect of physiological estrogen replacement. AB - To determine the effects of estrogen deficiency and replacement on GH secretion, we measured the 22-h GH secretory pattern and response to 1 h of light exercise in 16 normal postmenopausal women before and after treatment replacement with ethinyl estradiol (20 micrograms/day for 15 days). To determine whether the changes found were due to pituitary sensitization by estrogen, the response to synthetic GH-releasing hormone (GHRH; 1.0 microgram/kg, iv) was measured. To assess the biological effectiveness of GH in estrogen-treated women, somatomedin C (Sm-C) responses to GHRH were measured. Pre- and postestrogen GH secretion rates, expressed as mean areas circumscribed by plasma GH values, were as follows: 22-h study, 1.4 +/- 0.1 (+/- SEM) vs. 2.0 +/- 0.3 ng/ml X h (P = 0.04; n = 5); during 1 h of exercise, 2.3 +/- 0.4 vs. 3.2 +/- 0.4 ng/ml X h (P = 0.03; n = 16); after GHRH-(1-40), 6.7 +/- 1.7 vs. 8.5 +/- 1.5 ng/ml X h (P = 0.12; n = 16). There also was a modest but significant increase in resting plasma GH (1.5 +/- 0.2 vs. 2.3 +/- 0.5 ng/ml (P = 0.039). Pre- and postestrogen plasma Sm-C concentrations were 0.56 +/- 0.08 and 0.32 +/- 0.03 U/ml, respectively (P = 0.006; n = 16). Thus, estrogen therapy increased spontaneous and exercise-induced GH secretion in postmenopausal women and reduced Sm-C levels. The mechanisms of GH elevation by estrogen may include both central effects and a negative feedback linkage to reduced plasma Sm activity. PMID- 3088025 TI - Clinical implications of estimation of intact parathyroid hormone (PTH) versus total immunoreactive PTH in normal subjects and hyperparathyroid patients. AB - We describe a clinical study comparing the value of measurements of intact human PTH [hPTH(1-84)] and total PTH immunoreactivity [hPTH-(1-84) plus fragments]. A two-step immunochemical method was used to separate plasma hPTH-(1-84) from all circulating PTH fragments. The first step involved extraction and concentration of plasma PTH using solid phase antiamino-terminal PTH antibodies. After elution, the PTH immunoextract was analyzed using a sensitive mid- and C-region immunoassay. Complete separation in the immunoextraction step was proven by Sephadex G-75 gel filtration. hPTH-(1-84) values in fasting patients showed a clear distinction between those with primary hyperparathyroidism and those with nonparathyroid hypercalcemia, in contrast with small overlap in total immunoreactive PTH values. The hPTH-(1-84) values increased faster and more substantially in response to long EDTA and calcium infusion tests, compared with total PTH immunoreactivity, in normal subjects. Infusion of EDTA (10 mg/kg BW) in 5 min) elicited a readily measurable response of hPTH-(1-84) between 5 and 10 min after starting the infusion. Ingestion of 1000 mg calcium caused a decrease in hPTH-(1-84) in 1 h or less. More than 50% of patients with terminal renal failure had normal hPTH-(1-84) values despite elevated total immunoreactive PTH concentrations. We conclude that the two-step hPTH-(1-84) assay is more specific and sensitive than most regional PTH assays. Measurements of hPTH-(1-84) levels may identify disorders of parathyroid function at an early stage and provide a useful tool for the study of parathyroid physiology. PMID- 3088026 TI - Growth hormone (GH) and prolactin responses to repetitive administration of GH releasing hormone in acromegaly. AB - We investigated the pattern of GH secretion in response to repetitive GH releasing hormone (GHRH) administration in patients with active acromegaly and in normal subjects. Twelve acromegalic patients (nine women and 3 men; aged 21-76 yr) were studied. Eight had never been treated, whereas four had undergone neurosurgery but still had active disease. All patients and eight normal subjects received three doses of 50 micrograms GHRH, iv, at 2-h intervals. Seven patients were retested 6-8 weeks after transsphenoidal removal of a pituitary adenoma. There was a marked serum GH rise in acromegalic patients and normal subjects after the first GHRH dose [area under the curve, 2070 +/- 532 (+/- SE) vs. 1558 +/- 612 ng/min X ml, respectively; P = NS]. Successive GHRH doses stimulated GH release only in acromegalic patients (second dose, 1123 +/- 421 ng/min X ml; third dose, 2293 +/- 1049 ng/min X ml). In normal subjects, the GH response to the second and third GHRH doses was blunted (second dose, 86 +/- 32 ng/min X ml; third dose, 210 +/- 63 ng/min X ml; P less than 0.01). PRL secretion did not change in normal subjects, whereas 6 of 12 acromegalic patients had PRL release after each GHRH dose (PRL responders to GHRH). Transsphenoidal surgery led to normalization (less than 5 ng/ml) of the preoperatively elevated GH levels in all but 2 patients, who, however, had reduction of somatomedin-C levels. The amount of GH released in the postoperative test was significantly lower than that released preoperatively (first dose, 722 +/- 209 vs. 2945 +/- 743 ng/min X ml; second dose, 358 +/- 117 vs. 1737 +/- 633 ng/min X ml; third dose, 320 +/- 144 vs. 1776 +/- 676 ng/min X ml, respectively; P less than 0.05 in all instances). Thus, patients with active acromegaly, but not normal subjects, respond to repetitive GHRH administration at 2-h intervals with an increase in GH levels. This increase may be due to a larger releasable GH pool and/or faster GH turnover in the adenomatous cell. PMID- 3088027 TI - Thyrotropin-releasing hormone cannot be detected in plasma from normal subjects. AB - Different laboratories report widely varying average levels of TRH in plasma from normal man. However, arguments can be raised against the methods used to characterize the substances measured in all previous studies. Using a sensitive RIA and methanol extraction, immunoreactive TRH (iTRH) in serum from normal subjects averaged 49 +/- 26 pg/ml (mean +/- SD; n = 6). When SP-Sephadex purification was introduced, iTRH decreased to 1.8 +/- 0.7 pg/ml. These low quantities did not further decrease when incubated with TRH-degrading enzymes, demonstrating that the remaining iTRH was not identical to synthetic TRH. Investigations of iTRH in pools of normal plasma indicate that the level of true TRH in normal human plasma is below 0.4 pg/ml. PMID- 3088028 TI - Selection of a reference lot of Mueller-Hinton agar. AB - A collaborative study was undertaken to evaluate the performance of currently marketed Mueller-Hinton agars from seven manufacturers by replicate disk diffusion tests with standard quality control strains. Identification of the manufacturers was concealed, and the resulting data were evaluated for the selection of a physical reagent standard against which the performance of future production lots would be tested and made to conform. A medium was selected which was sufficiently close to existing National Committee for Clinical Laboratory Standards quality control limits that current interpretive criteria would require minimum modification. Two of the seven lots were eliminated from further consideration because the final pHs were outside acceptable limits. The remaining four lots had 96% of mean zone diameters less than or equal to 2 mm from those of the chosen lot and 65% of the means were less than or equal to 1 mm from those of the chosen lot for all 28 antimicrobial agent-organism combinations. Manufacturers then attempted to produce new lots of Mueller-Hinton agar which performed within the prescribed limits of the chosen lot. One lot performed in close conformity with the selected standard, but the overall performance of the media was essentially the same as that of the randomly chosen lots in the initial study. It was concluded that one of the original seven lots demonstrated properties which made it a tentative candidate for a physical reagent standard and that the use of a physical reagent standard in evaluating production lots might aid in stabilizing the performance of Mueller-Hinton agar. PMID- 3088030 TI - Preliminary evaluation of a rapid colorimetric method for identification of pathogenic Neisseria. AB - A rapid colorimetric method for the identification of pathogenic Neisseria (Identicult-Neisseria; Scott Laboratories, Inc.) based on beta-galactosidase, gamma-glutamylaminopeptidase, and gamma-prolylaminopeptidase is described. All 82 clinical isolates of Neisseria gonorrhoeae, 9 clinical isolates of N. meningitidis, and 5 clinical isolates of N. lactamica were correctly determined to the species level, as were 4 isolates of Branhamella catarrhalis. Reactions were prompt and easily interpreted. The system should be extremely useful in clinical laboratories. PMID- 3088029 TI - Identification of Mycobacterium tuberculosis antigens in Seibert fractions by immunoblotting. AB - Seibert fractions prepared from Mycobacterium tuberculosis culture filtrates were evaluated by immunoblotting with a serum pool from patients with active pulmonary tuberculosis. Antibody activity was observed primarily with antigens in the polysaccharide II and A protein fractions; these fractions were further evaluated by immunoblotting with sera from individual patients with tuberculosis, from individuals without tuberculosis and positive for the purified protein derivative antigen skin test, and from individuals negative for the purified protein derivative antigen skin test. The antigens identified in the protein A fraction, a 32,000-molecular-weight antigen and a heterogeneous high-molecular-weight antigen, reacted with antibody found in sera from all patients with tuberculosis and with antibody from over 25% of the control individuals. A 10,000-molecular weight antigen, a 30,000- to 44,000-molecular-weight antigen, and a heterogeneous high-molecular-weight antigen were observed in the polysaccharide II fraction; these antigens reacted with serum antibody from 70% or more of the patients with tuberculosis and with antibody from 20 to 70% of the control individuals. One of the antigens, with a molecular weight ranging from 17,000 to 28,000 in the polysaccharide II fraction, reacted with antibody in 64% of the sera from patients with tuberculosis but with only 1 of 15 control normal sera. This antigen may elicit an antibody response specifically associated with tuberculosis. PMID- 3088031 TI - Increased detection of prolylaminopeptidase in Neisseria meningitidis by Identicult-Neisseria. AB - Identicult-Neisseria (Scott Laboratories, Inc., Fiskeville, R.I.), a rapid enzymatic method with chromogenic substrates, was tested in our laboratories for the identification of Neisseria gonorrhoea, Neisseria meningitidis, and Neisseria lactamica. The test correlated very highly in its identification of pathogenic Neisseria spp. with modified New York City fermentation medium. Identicult Neisseria appeared to be more sensitive in its detection of prolylaminopeptidase activity in N. meningitidis than most of the currently available systems. PMID- 3088032 TI - Evaluation of a commercially available direct immunofluorescent staining reagent for the detection of respiratory syncytial virus in respiratory secretions. AB - A commercially-available direct immunofluorescence (IF) reagent (Imagen; Boots Celltech, Slough, Berkshire, United Kingdom) was similar in sensitivity and specificity to the conventional indirect IF test for the detection of respiratory syncytial virus in respiratory secretions. Both IF tests were more sensitive than culture, particularly for specimens transported from outside the institution. PMID- 3088033 TI - Detection of mycobacterial antigens in leprosy serum immune complex. AB - The antigens from immune complexes of sera from patients with mycobacterial diseases were released by sodium dodecyl sulfate. The antigenic activity of the released proteins was tested by agar gel diffusion and immunoelectrophoresis. This simple method provided direct evidence for the presence of mycobacterial antigens in the immune complexes of sera from patients with leprosy and tuberculosis. PMID- 3088034 TI - Elucidation of Strongyloides stercoralis by bacterial-colony displacement. AB - Two cases of unsuspected Strongyloides stercoralis infection were elucidated by the displacement of bacterial colonies on primary plating media. Observation of primary plates inoculated for the diagnosis of bacterial pneumonia or gastroenteritis revealed that normal flora colonies had been moved and were aligned in a pathway, or track. This unusual colony alignment prompted us to request a stool for the examination of parasites, and S. stercoralis was found. It was concluded that the parasite is capable of motility on agar surfaces, resulting in the displacement of bacterial colonies that make up the normal flora. PMID- 3088035 TI - Antigenic characteristics and serological identification of 10 black-pigmented Bacteroides species. AB - Strains of 10 black-pigmented Bacteroides species were serologically characterized using absorbed and unabsorbed rabbit antisera. An agglutination test using intact cells or heated cells (100 degrees C for 60 min) from each species and unabsorbed antisera revealed only homologous reactions with little or no reactivity in heterologous assays. Immunodiffusion tests using sonicated antigen demonstrated that Bacteroides gingivalis, B. endodontalis, B. asaccharolyticus, B. macacae, and B. levii are antigenically distinct. Strains of B. gingivalis, B. endodontalis, and B. asaccharolyticus were also clearly identified by the indirect immunofluorescent antibody method. B. intermedius, B. corporis, B. loescheii, B. melaninogenicus, and B. denticola possessed common antigens; however, species-specific antigens detectable with immunoabsorbed antisera were also demonstrated. B. intermedius strains isolated from the human oral cavity included at least two serogroups. In each black-pigmented Bacteroides species, lipopolysaccharide constituted one of the species-specific antigens. PMID- 3088036 TI - Evaluation of the GO Slide (Roche) growth transport system for isolation of Neisseria gonorrhoeae from clinical specimens. AB - A new growth transport system for the isolation of Neisseria gonorrhoeae from clinical specimens was evaluated. The system, GO Slide (Roche) of F. Hoffmann-La Roche & Co., Basel, Switzerland, showed 88% sensitivity for male urethral specimens and 59% sensitivity for endocervical specimens compared with transport in the Amies transport medium combined with culturing on modified Thayer-Martin medium. The media used appear not to support growth of certain strains of N. gonorrhoeae. recovery and growth-supporting capabilities of this system need to be improved before the system can be used routinely. PMID- 3088038 TI - Petit mal epilepsy: a review and integration of recent information. AB - Petit mal (absence) epilepsy remains one of the most enigmatic of neurological disorders, and there is no widely accepted theory of its etiology. This review covers some of the current issues concerned with the disorder, including treatment and prognosis, neurochemical research, behavioral and psychophysiological effects of wave-spiked discharges, and EEG studies of seizure control. With respect to treatment, although effective drug therapy (valproic acid, ethosuximide) exists for the "pure" form of absence epilepsy, other forms, in which there is an admixture of grand mal seizures, are less amenable to pharmacotherapy. Moreover, the frequency of fatal hepatic toxicity following valproic acid therapy has been estimated at 1 in 20,000. With respect to prognosis, follow-up studies indicate that many patients do not outgrow the disorder but continue to suffer absence seizures well into adulthood. In recent years, there has been considerable research on the neurochemical basis of absence epilepsy. Current theories, including those that implicate gamma-aminobutyric acid, catecholamines, and "endogenous" epileptogens, are summarized; and requirements for an experimentally induced animal model of absence epilepsy are discussed. The majority of behavioral studies of the disorder have concerned the effects of petit mal-type discharges on sensory and cognitive processes. Some of these studies are reviewed; and recent work bearing on these issues, involving event-related brain potentials, is presented. Our review concludes with a discussion of research aimed at the development of electrophysiologically based approaches to the reduction of seizure frequency in patients with absence epilepsy. PMID- 3088037 TI - Microplate technique to determine hemolytic activity for routine typing of Listeria strains. AB - Because the hemolysis produced by Listeria monocytogenes and Listeria seeligeri on blood agar is frequently difficult to interpret, we developed a microplate technique for the routine determination of hemolytic activity with erythrocyte suspensions. This microtechnique is a simple and reliable test for distinguishing clearly between hemolytic and nonhemolytic strains and could be used instead of the CAMP (Christie-Atkins-Munch-Petersen) test with Staphylococcus aureus in the routine typing of Listeria strains. Furthermore, our results suggest that the quantitation of the hemolytic activity of the Listeria strains, along with the D xylose, L-rhamnose, and alpha-methyl-D-mannoside acidification tests, allows the differentiation of L. monocytogenes, L. seeligeri, and Listeria ivanovii. We also observed that the treatment of erythrocytes with crude exosubstances of rhodococcus equi, Pseudomonas fluorescens, Acinetobacter calcoaceticus, and S. aureus enhanced the hemolytic activity of all Listeria strains with this characteristic. PMID- 3088039 TI - Opportunistic infections in acquired immune deficiency syndrome result from synergistic defects of both the natural and adaptive components of cellular immunity. AB - We evaluated the cellular immunity of 408 clinically stratified subjects at risk for acquired immune deficiency syndrome (AIDS), to define the role of interferon alpha production deficits in the pathogenesis of opportunistic infections (OI). We followed 115 prospectively for up to 45 mo. Onset of OI was associated with, and predicted by, deficiency both of interferon-alpha generation in vitro, and of circulating Leu-3a+ cells. Interferon-alpha production is an index of the function of certain non-T, non-B, large granular lymphocytes (LGL) that are independent of T cell help. Leu-3a+ cell counts are a marker of T cell function. OI did not usually develop until both of these mutually independent immune functions were simultaneously critically depressed, leading to a synergistic interaction. These data suggest that the AIDS virus affects a subset of LGL, and that cytokine production by these cells is an important component of the host defense against intracellular pathogens that becomes crucial in the presence of severe T cell immunodeficiency. PMID- 3088040 TI - Influence of the fast-acting inhibitor of plasminogen activator on in vivo thrombolysis induced by tissue-type plasminogen activator in rabbits. Interference of tissue-derived components. AB - The influence of endotoxin-induced elevated plasma levels of the fast-acting inhibitor of plasminogen activator (PA-inhibitor) on thrombolysis was investigated in rabbits with a jugular vein thrombus. Infusion of human tissue type plasminogen activator (t-PA) produced similar degrees of thrombolysis in control and endotoxin-treated rabbits, although no free t-PA could be demonstrated in plasma of endotoxin-treated animals. Infusion of t-PA in an extracorporeal arteriovenous shunt resulted in loss of thrombolytic activity in endotoxin-treated animals but not in control animals. Blood clots superfused in vitro with mixtures of t-PA and normal plasma lysed in contrast to clots superfused with t-PA and PA-inhibitor-rich plasma. However, addition of rabbit lung slices to the plasma surrounding the blood clot, reversed the inhibition of thrombolysis by PA-inhibitor-rich plasma. This indicates that tissue-derived factor(s) are involved in the regulation of in vivo thrombolysis. These hypothetical factor(s) are, however, very unstable in plasma, which has thus far precluded their further characterization. PMID- 3088041 TI - Localization of the binding site of tissue-type plasminogen activator to fibrin. AB - Functionally active A and B chains were separated from a two-chain form of recombinant tissue-type plasminogen activator after mild reduction and alkylation. The A chain was found to be responsible for the binding to lysine Sepharose or fibrin and the B chain contained the catalytic activity of tissue type plasminogen activator. An extensive reduction of two-chain tissue-type plasminogen activator, however, destroyed both the binding and catalytic activities. A thermolytic fragment, Fr. 1, of tissue-type plasminogen activator that contained a growth factor and two kringle segments retained its lysine binding activity. Additional thermolytic cleavages in the kringle-2 segment of Fr. 1 caused a total loss of the binding activity. These results indicated that the binding site of tissue-type plasminogen activator to fibrin was located in the kringle-2 segment. PMID- 3088042 TI - Gentamicin and gram-negative bacteremia. A synergism for the development of experimental nephrotoxic acute renal failure. AB - To explore whether bacteremia potentiates gentamicin nephrotoxicity, we injected rats with either 1 X 10(9) Escherichia coli (E. coli), Pseudomonas aeruginosa, or Staphylococcus aureus, and then gave them gentamicin, 100 mg/kg. Renal injury was assessed over the next 24-48 h. Staphylococcus/gentamicin or gentamicin alone induced no renal injury. However, E. coli/gentamicin and Pseudomonas/gentamicin caused acute renal failure (severe azotemia; tubular necrosis; cast formation). This effect was not due to acute reductions in arterial blood pressure or renal blood flow, it could be reproduced by substituting nonviable for viable gram negative organisms, and it was associated with increased renal gentamicin uptake. E. coli without gentamicin induced only mild azotemia and no tubular necrosis. Endotoxin-tolerant rats were significantly protected against the E. coli/gentamicin nephrotoxic interaction. We conclude that gram-negative bacteremia and gentamicin exert synergistic nephrotoxicities; and that this effect is mediated, at least in part, by endotoxin and in part by increased renal gentamicin uptake. PMID- 3088043 TI - Transplantation of normal bone marrow into a pig with severe von Willebrand's disease. AB - Bone marrow from a normal male pig was transplanted into a related female pig with severe homozygous von Willebrand's disease (vWd). After engraftment the circulating leukocytes were of the male karyotype, and the platelets were strongly positive for von Willebrand factor (vWF) by indirect immunofluorescence. The average level of vWF was 1.96 U/dl and of ristocetin cofactor was 2.8 U/dl. The ear immersion bleeding time before transplantation was consistently more than 15 min and afterwards varied between 5 min and more than 15 min. Transfused vWF corrected the bleeding time at a level of 10 U/dl, which is lower than that required for a von Willebrand pig. We concluded that: the plasmatic compartment is only minimally replenished by the vWF from platelets and megakaryocytes; and the platelet vWF alone only partially corrects the abnormal tests of the hemostatic mechanism in severe vWd. PMID- 3088044 TI - Biochemical selectivity of oral versus intravenous aspirin in rats. Inhibition by oral aspirin of cyclooxygenase activity in platelets and presystemic but not systemic vessels. AB - In rats intravenous aspirin was only slightly more effective an inhibitor of platelet thromboxane B2 (TxB2) than of aorta 6-keto-prostaglandin (PGF)1 alpha generation (1.9 versus 2.1 mg/kg). In contrast, oral aspirin was about five times more effective on platelet than on aorta cyclooxygenase activity. The "biochemical selectivity" of aspirin as an inhibitor of platelet and vascular cyclooxygenase thus was not apparent after intravenous administration of the drug. However, this could be achieved by relatively low doses of oral (or intraduodenal) aspirin, on account of "presystemic" acetylation of platelet cyclooxygenase. Even in this condition, though, aspirin selectivity was relative to "systemic" peripheral vessels but not to the vessels of the enterohepatic circulation. Indeed after an oral or intraduodenal dose of 5 mg/kg aspirin, generation of portal vein 6-keto-PGF1 alpha was inhibited to much the same extent as platelet TxB2, while inferior vena cava 6-keto-PGF1 alpha formation was spared. PMID- 3088045 TI - Neurofibromatosis: implications for learning and behavior. AB - Learning and behavior problems occur frequently in children with neurofibromatosis (NF), although, to the best of our knowledge, no one has described the types of problems encountered. This paper presents psychological test data on 23 NF children referred to a Learning Disorders Clinic. A high incidence of visual-perceptual disability was found in isolation (56%) or in conjunction with language deficits (30%). This pattern was found to differ from that seen in children with developmental learning disorders, without NF. The need for physicians to incorporate questions about learning and behavior into their history-taking process is stressed. PMID- 3088046 TI - The effects of behavior modification vs lithium therapy on frontal lobe syndrome. AB - An A-B-BC-C single-subject design was used to evaluate the effects of behavior modification (i.e. a token economy program) and lithium therapy on the behavioral symptoms associated with frontal lobe damage in a 21-year-old woman. The design consisted of a baseline, token economy, token economy plus lithium, lithium alone and a 4 month follow-up. There was a significant decrease in inappropriate behaviors after treatment with the token economy program, but no additional change was noted in subsequent phases involving lithium therapy. There was evidence of generalization and maintenance in the home environment, even after lithium therapy was discontinued. The results do not support the use of a combined treatment approach. PMID- 3088047 TI - Varied citrus treatment of ruminant gagging in a teenager with Batten's disease. AB - Chronic ruminant gagging was substantially reduced in a severely retarded 13-year old girl with Batten's disease through the use of contingent citrus juice in an ABAB design. Previous literature suggests that citrus juice may not be effective for treatment of rumination in older and/or handicapped children due to habituation. In this study, habituation may have been prevented by alternating lime juice and lemon juice when ruminative gagging reached a predetermined rate. The lemon/lime variation offers an effective, practical, and acceptable alternative to other response suppression procedures for rumination. PMID- 3088048 TI - Sonographic monitoring of LHRH analogue therapy in idiopathic precocious puberty in young girls. AB - Precocious puberty in young girls is defined as the development of secondary sexual characteristics and gonadal growth before 8 years of age. Approximately 60% of isosexual precocious development in girls has no organic cause and is termed idiopathic precocious puberty. Thirteen young girls with idiopathic precocious puberty were treated with LHRH analogue under a well-established protocol. Pelvic ultrasound was added to the protocol to examine ultrasound's role in supplying a morphologic parameter of suppression of the pubertal process. Initially, 11 patients had ovarian volumes greater than normal, and ovarian cysts measuring 0.5 cm to 4 cm in diameter were identified in seven patients. All 13 patients had enlarged pretreatment uteri greater than 3 cm in length. Eleven of these patients had a pubertal or adult uterine configuration. After 1 year of therapy, 11 patients had normal prepubertal ovarian volumes, and 12 of 13 patients had a decrease in ovarian volume. No demonstrable cysts were present at 1 year. Eleven had a reduction in uterine length. Nine of the 11 patients with a pubertal uterine configuration reverted to a more prepubertal-like morphology. The sonographic morphologic changes correlated well with laboratory and clinical data indicating suppression of the hypothalamic-pituitary-gonadal axis. PMID- 3088049 TI - Differential diagnosis of anechoic/hypoechoic lesions in the abdomen detected by ultrasound. AB - Ultrasound is the method of choice in the detection and differentiation of solid or cystic masses in the abdomen. The differential diagnosis of anechoic and hypoechoic lesions comprises a large variety of benign and malignant diseases or abnormalities. This paper describes a number of such lesions and, in addition, discusses the possible differential diagnoses so far reported in the literature. An attempt is made to describe the different features of such lesions. Most of them are rare but have to be considered if a lesion of unknown origin or clinical relevance is detected by ultrasound. PMID- 3088050 TI - Ultrasonographic detection of the patellar plica in the knee. AB - In 39 knees of 38 patients, an ultrasonographic investigation of the patellofemoral space was performed to detect a plica synovialis. By arthroscopic control, we found a sensitivity for the ultrasonographic method of 92% and a specificity of 73%. The method, materials, and results are discussed in this paper. PMID- 3088051 TI - Procedural hazards of neonatal ultrasonography. AB - Neonatal ultrasonography entails potential procedural hazards to the newborn infant. When performing ultrasound studies, the examiner may inadvertently move the endotracheal tube or may facilitate the spread of infection from one baby to another. The examiner should also be aware that the pressure of applying the transducer to the scalp is transmitted to the central nervous system and that the baby may become hypothermic during the procedure. Precautions include minimizing head and neck movement and application of pressure on the fontanel, using prewarmed coupling gel, which is removed after scanning, careful handwashing, and wiping the transducer with 70% isopropyl alcohol or 2% alkalinized glutaraldehyde between studies. PMID- 3088052 TI - Digital averaging to facilitate two-dimensional echocardiographic measurements. AB - A problem in quantitative two-dimensional echocardiography is myocardial dropout of still frame images. This study was designed to evaluate the ability of digital averaging to overcome myocardial dropout without distorting quantitative measurements. Forty-one percent of 80 digitally averaged images were thought to be improved by five independent observers, whereas 7% showed some deterioration. Measurements obtained from processed images were statistically identical (r greater than or equal to 0.9) to those from three arithmetically averaged, unprocessed images in 60 patients. Digital averaging can improve image quality without measurement distortion and should facilitate two-dimensional echocardiographic quantitation. PMID- 3088053 TI - Sonographic patterns of carotid body tumors. PMID- 3088054 TI - Echogenic wound abscess mimicking hepatic mass on ultrasonography. PMID- 3088055 TI - Sonographic diagnosis of lethal osteogenesis imperfecta in the second trimester: case report and review. PMID- 3088057 TI - Sonographic diagnosis of rhabdomyolysis. PMID- 3088056 TI - Fetal neck hemangioendothelioma with secondary hydrops fetalis: sonographic diagnosis. PMID- 3088058 TI - Sonographic and pathologic correlation in intussusception of the bowel. PMID- 3088059 TI - Lipomatosis of the pancrease: mistake in diagnostic imaging. PMID- 3088060 TI - Hepatic artery aneurysm: ultrasonic diagnosis. PMID- 3088061 TI - Fetal small bowel simulating an abdominal mass at sonography. AB - A focal, well-marginated, homogeneous hyperechoic mass was identified within the fetal abdomen of five early gestations varying in age from 16 to 20 weeks ECA (estimated conceptual age). Initially, the possibility of a congenital abdominal tumor mass was raised. Serial sonography subsequently demonstrated progressive dissolution of the masses, each of which assumed the characteristic appearance of normal small bowel by 30 weeks ECA. The recognition of this normal fetal small bowel maturation pattern is important lest it be confused with congenital retroperitoneal or gastrointestinal tract abnormalities. PMID- 3088062 TI - Production of microbubbles for use as echo contrast agents. AB - A variety of agents have been proposed for use as contrast for ultrasound studies. Several reports suggest the use of microbubbles because of their superior sonographic resolution. We describe a method of producing calibrated microbubbles utilizing differential absorption and gas injection techniques. Gas injection methods are described using a Plexiglas microbubbler apparatus with a fine needle orifice. The bubbles originally produced by this device are in a size range of 40-100 microns and consist of nitrogen (10%) and carbon dioxide (90%). The differential absorption technique uses THAM [tris(hydroxymethyl)aminomethane hydrochloride] to absorb the carbon dioxide (diluent gas) from the bubbles selectively, leaving smaller microbubbles. The microbubbles can be calibrated using the electric gating principle of the Coulter Counter. PMID- 3088063 TI - Mast cell sarcoma of the larynx. AB - A 74 year old woman presented with a primary subglottic tumour. Neither cutaneous mastocytosis (urticaria pigmentosa) nor spread to the bone marrow, liver, or spleen were detected. About two years after initial manifestation of the tumour nodular skin metastases appeared, as well as local recurrence in the larynx. Despite chemotherapy and radiation the disease progressed and was fatal. The terminal phase was characterised by generalisation of the mast cell tumour with diffuse infiltration of bone marrow and, shortly before death, leukaemic transformation. The patient died four years after onset of disease with symptoms of a hemorrhagic diathesis. As far as we know this is the first case of mast cell sarcoma to be reported in man. PMID- 3088064 TI - Biochemical and cultural characteristics of "JK" coryneforms. AB - Antibiotic resistant coryneforms (group JK) have increasingly been reported as causes of serious sepsis in the immunosuppressed and in patients with implants. Their cultural and biochemical characteristics were examined in an attempt to provide a simple scheme for their recognition in the clinical laboratory. Their susceptibilities to a range of antimicrobials were determined, and an enriched selective medium was developed for their isolation from normally non-sterile sites. The JK coryneforms fell into a fairly homogeneous group, producing colonial morphology and biochemical profiles identical with reference strains, which allowed their recognition and differentiation from other coryneforms. All strains were resistant to penicillin and susceptible to vancomycin, but there was considerable variation with respect to other antimicrobials. There is scope for further rationalisation of biochemical tests for the recognition of these organisms. PMID- 3088065 TI - Organization of the callosal connections of visual areas V1 and V2 in the macaque monkey. AB - The interhemispheric efferent and afferent connections of the V1/V2 border have been examined in the adult macaque monkey with the tracers horseradish peroxidase and horseradish peroxidase conjugated to wheat germ agglutinin. The V1/V2 border was found to have reciprocal connections with the contralateral visual area V1, as well as with three other cortical sites situated in the posterior bank of the lunate sulcus, the anterior bank of the lunate sulcus, and the posterior bank of the superior temporal sulcus. Within V1, callosal projecting cells were found mainly in layer 4B with a few cells in layer 3. Anterograde labeled terminals were restricted to layers 2, 3, 4B, and 5. In extrastriate cortex, retrograde labeled cells were in layers 2 and 3 and only very rarely in infragranular layers. In the posterior bank of the lunate sulcus, labeled terminals were scattered throughout all cortical layers except layers 1 and 4. In the anterior bank of the lunate sulcus and in the superior temporal sulcus, anterograde labeled terminals were largely focused in layer 4. Callosal connections in all contralateral regions were organized in a columnar fashion. Columnar organization of callosal connections was more apparent for anterograde labeled terminals than for retrograde labeled neurons. In the posterior bank of the lunate sulcus, columns of callosal connections were superimposed on regions of high cytochrome activity. The tangential extent of callosal connections in V1 and V2 was found to be influenced by eccentricity in the visual field. Callosal connections were denser in the region of V1 subserving foveal visual field than in cortex representing the periphery. In V1 subserving the fovea, callosal connections extended up to 2 mm from the V1/V2 border and only up to 1 mm in more peripheral located cortex. In area V2 subserving the fovea, cortical connections extended up to 8 mm from the V1/V2 border and only up to 3 mm in peripheral cortex. PMID- 3088067 TI - Platelet measurements in the common marmoset, Callithrix jacchus. AB - Platelet counts and mean platelet volumes were determined for 39 male and 32 female adult marmoset whole blood samples and these results are compared with previously published data. There is no evidence of a difference between sexes but there is some evidence of a relationship between platelet count and mean platelet volume in the Callithrix jacchus population studied. PMID- 3088066 TI - Neuropeptide-FMRFamide-like immunoreactivity in Drosophila: development and distribution. AB - Neuropeptide-FMRFamide-like immunoreactivity was characterized in the fruit fly, Drosophila melanogaster. In the adult central nervous system, a stereotypic pattern of immunoreactive cell bodies and immunoreactive nerve processes and varicosities was observed, indicating a neurochemical role for FMRFamide-like substance(s) in Drosophila. Localization of immunoreactivity in the central nervous system of early larval stage revealed that the majority of the prominent FMRFamide-like immunoreactive neurons were already differentiated. The FMRFamide like immunoreactive neurons remain immunoreactive throughout postembryonic stage and persist in the adult central nervous system. In the larva, in addition to the central nervous system, FMRFamide-like immunoreactivity was localized in the fibers innervating the ring gland, in the ganglion innervating the gut and in the gastric caeca. PMID- 3088068 TI - Serum protein electrophoretic patterns of the marmoset, Callithrix jacchus. AB - Three electrophoretic procedures were used to separate protein fractions of marmoset serum. The albumin of marmoset serum migrated further than that of human serum with all three procedures and the number and size of the globulin fractions differed with species and with procedure. PMID- 3088069 TI - Leu-8 and Leu-9 antigen phenotypes: immunologic criteria for the distinction of mycosis fungoides from cutaneous inflammation. AB - The distinction of mycosis fungoides from reactive cutaneous inflammation can be difficult. Unfortunately, since many reactive processes exhibit predominantly a mature helper T cell phenotype similar to that expressed by most cases of mycosis fungoides, standard immunologic marker studies have not been very helpful in differential diagnosis. To determine whether novel immunophenotypic criteria could be developed that correlate with the diagnosis of cutaneous involvement by mycosis fungoides, we studied the expression of Leu-8 and Leu-9 antigens by T cells in forty-one skin biopsy specimens from twenty-seven patients with mycosis fungoides and thirty-four skin biopsy specimens from thirty-three controls with a variety of benign cutaneous diseases. These antigens are expressed by the majority of normal T cells in the blood and lymphoid tissues but are often absent in T cell lymphomas or expressed by only a minority of tumor cells. Semiquantitative grading of the percentage of Leu-8+ and Leu-9+ T cells in our patients revealed that deficiency of these antigens (i.e., expression by less than or equal to 33% of T cells) was more prevalent among mycosis fungoides patients than among controls and became more specific for mycosis fungoides as the percentage of Leu-8+ and Leu-9+ T cells decreased. In initial biopsies, less than or equal to 33% of T cells were Leu-8+ in 82% of mycosis fungoides patients versus 15% of controls, while less than or equal to 10% of T cells were Leu-8+ in 52% of mycosis fungoides patients versus only 3% of controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3088070 TI - Nodular primary localized cutaneous amyloidosis: immunohistochemical evaluation and treatment with the carbon dioxide laser. AB - Nodular primary localized cutaneous amyloidosis is an uncommon disorder for which there is no consistently satisfactory treatment. The amyloid fibrils are thought to have an immunoglobulin light chain derivation and systemic involvement must be excluded in all cases. We report a patient with a large scalp lesion of nodular primary localized cutaneous amyloidosis whose immunohistochemical evaluation revealed lambda light chain deposits and who thus far has no apparent systemic involvement. The lesion was treated by the carbon dioxide (CO2) laser with excellent cosmetic results and minimal morbidity. PMID- 3088071 TI - Juvenile xanthogranulomas and xanthoma disseminatum--variations on a single theme. PMID- 3088072 TI - Effects of CO2 inhalation on acid-base balance and thermal recovery following cold water dives by the muskrat (Ondatra zibethicus). AB - Thermoregulatory, cardiac, and blood gas responses of muskrats to CO2 inhalation were examined during recovery from controlled dives in 3 degrees C water. It was shown that CO2 levels previously recorded in the winter lodges of this species are sufficient to reduce postdive oxygen consumption and rate of rewarming in unrestrained animals. Postdive exposure to 5-10% CO2 reduced recovery of abdominal and subcutaneous temperature (Tb) in the middorsal lumbar region, but did not affect interscapular warming overlying brown adipose tissue. Depressed recovery of deep Tb was matched by a prolonged acidosis in restrained muskrats breathing 5-10% CO2 following 90-s submergence in 3 degrees C water. This occurred despite a comparatively high whole body buffer value (delta H+/delta PaCO2) of 0.53 nM X l-1 X mmHg-1. Protracted recovery of arterial pH did not appear to involve retention of CO2 accumulated during diving, since in all trials, PaCO2 returned to the predive baseline within 5 min of surfacing. Perturbations in PaO2, like PaCO2, were restored within 5 min of surfacing, irrespective of inspired gas mixture. Predive exposure to 5-10% CO2 had no discernible effect on establishment of bradycardia in diving muskrats. Compared to predive values, postimmersion heart rate was significantly reduced in 5-10% CO2, but not in control runs. PMID- 3088073 TI - Heart rates and gas exchange in the Amazonian manatee (Trichechus inunguis) in relation to diving. AB - Unrestrained Amazonian manatees (Trichechus inunguis) maintained a constant heart rate during diving and exhibited a slight tachycardia during breathing. 'Forcing' the manatees to dive caused a marked bradycardia. They exhibited a more pronounced tachycardia during breathing after 'forced' dives and hyperventilated during recovery dives. Manatees are capable of dives exceeding 10 min duration without having to resport to anaerobic metabolism, and even after 10 min dives recover within 3-4 short dives. The ability of manatees to make long dives, in spite of relatively poor O2 stores, is due to their low metabolic rate, while the rapid recovery is aided by their high CO2 stores which minimizes CO2 storage in the body. In manatees the changes in alveolar O2 and CO2 pressure (PAO2 and PACO2) in relation to dive time are slower and more variable than in other marine mammals. The lower rate of change is probably due to the manatees' reduced metabolic rate, while the greater variability is due to their breathing pattern, in which both ventilation and body gas stores influence alveolar gases. PMID- 3088074 TI - Determination of the extracellular lipases of Pseudomonas fluorescens spp. in skim milk with the beta-naphthyl caprylate assay. AB - A method based on the hydrolysis of beta-naphthyl caprylate (beta-NC) has been developed for quantitating extracellular lipase from Pseudomonas fluorescens. The assay was extremely sensitive to skim milk (SM); as little as 0.02 ml raw SM in a 2.0 ml reaction mixture resulted in an apparent loss of 50% of the lipase activity. Activity improved 3-fold when trypsin (50 micrograms/ml) was included in the reaction mixture. When super-simplex optimization was used to determine the optimum levels of beta-NC, Na taurocholate (NaTC), SM/lipase mixture and trypsin for maximum activity, NaTC was found to be unnecessary for activity. Subsequent addition of 15 mM-NaTC resulted in 80% loss of activity. On the other hand, NaTC was required for native lipase activity in the presence of SM. Native lipase was completely inhibited by heating at 70 degrees C for 2 min, while B52 lipase retained 75% of its activity under the same conditions. The assay was able to detect lipase produced by Ps. fluorescens B52 in SM at 5 degrees C when the cell density exceeded 10(8) colony forming units/ml. The presence of butterfat (3.5%) in the SM assay inhibited B52 lipase by 97%. The beta-NC assay gave results comparable to the tributyrin agar diffusion assay using cell-free extracts of ten strains of common dairy psychrotrophs. The results suggest that the beta-NC assay may be useful for determining lipase activity in raw SM. PMID- 3088075 TI - Conversion of glucose in lactase-hydrolyzed whey permeate to fructose with immobilized glucose isomerase. AB - The maximum conversion of glucose to fructose in lactase-hydrolyzed whey permeate by glucose isomerase was approximately 52% at .1 g enzyme/ml substrate after 7 h incubation at 60 degrees C. Removal of minerals from the substrate was essential for enzyme activity. The dependence of the enzyme on Mg++ and Co++ for activity in the presence of high ash concentration was demonstrated. Optimum Mg++ and Co++ additions were 250 and 100 ppm, respectively. The isomerization reaction was enhanced more when both 100 ppm Mg++ and 50 ppm Co++ were added. Hydrolyzed isomerized lactose whey syrup with sweetness equivalent to sucrose was successfully produced through enzymatic isomerization of glucose in lactase hydrolyzed whey permeate after supplementation with pure glucose. Fructose in hydrolyzed isomerized lactose whey syrup was effectively separated from other sugars by Dowex 1X8-200 anion exchange resin in the bisulfite form. PMID- 3088076 TI - Enterocin typing of enterococci isolated from dried infant foods. AB - One hundred and fifty enterococcal isolates recovered from 16 market samples of infant foods and 35 from other sources were characterized and subjected to enterocin typing with 18 indicator strains. Among 150 enterococcal isolates, 114 (76%) were able to be typed by the indicator strains. Although 24 enterocin patterns were observed with these enterococci, the most prevalent types were X-9, 224, and 65-603. Occurrence of pattern X-9 either singly or in combination with many other types was most frequent. Many of the enterocin patterns in enterococcal isolates were recovered from samples of dairy water supply and hand washings of personnel working in a dairy plant that manufactured infant food; this suggests the possibility of these as sources of contamination. Enterocin typing of enterococci could prove useful in epidemiological studies. PMID- 3088078 TI - Long-term catheter management: minimizing the problem of premature replacement due to balloon deflation. AB - Balloon deflation in long-term indwelling urinary catheters has been reported, and can necessitate a premature replacement of the catheter. This problem is studied in catheters of various materials and their performance in this respect compared. The catheters are also compared in terms of any change in effective shaft diameter. The results show that 100% silicone catheters perform significantly less well than silicone-coated latex ones on both parameters. The implications of these findings are discussed, and recommendations are made with regard to the selection of catheters for long-term use. PMID- 3088077 TI - Psychotherapeutic orientations: a comparison of conceptualizations, interventions, and treatment plan costs. PMID- 3088079 TI - The regulation of toxic air pollutants. A critical review. PMID- 3088080 TI - Evidence for deficiencies of conditionally essential nutrients during total parenteral nutrition. PMID- 3088081 TI - Taurine as a conditionally essential nutrient in man. PMID- 3088082 TI - Taurine supplementation in infants receiving long-term total parenteral nutrition. AB - Twenty-one children and 23 adults receiving long-term total parenteral nutrition (TPN) for 27 +/- 23 (SD) months were investigated to determine if they were taurine-deficient because the TPN solutions were taurine-free. The fasting plasma taurine level was reduced in the children to 26 + 13 mumol/liter vs the control 57 +/- 16 mumol/liter (P greater than 0.001). The plasma taurine level was significantly reduced in those adults who absorbed less than 25% of their nutritional needs from their diet. Electroretinograms were abnormal in each of eight children who were examined; isolated cone and rod implicit times were both significantly delayed. Electroretinograms were not abnormal in those adults with low plasma taurine levels. Taurine was added to the TPN solutions of four children, and the plasma taurine level became normal in each of them. Electroretinograms of three of these children became normal. One year after discontinuing intervenous taurine supplementation, the plasma taurine level became abnormal in two of three children. These observations indicate that children, and possibly adults, receiving long-term TPN have a nutritional requirement for taurine. PMID- 3088083 TI - Conditional deficiencies of ornithine or arginine. AB - Relative deficiencies of ornithine or arginine occur in the presence of excessive ammonia, excessive lysine, growth, pregnancy, trauma, or protein deficiency and malnutrition. Ammonia excess may occur in the presence of a normal liver when amino acid mixtures lacking ornithine, arginine, or citrulline are infused; when specific amino acids such as glycine are injected; when ammonium salts, urea, or urease are injected; or when the gastrointestinal tract contains an excess of protein, urea, or NH4+, as occurs after a gastrointestinal hemorrhage. In these states, ornithine is often rate-limiting for urea cycle function. Ornithine is also rate-limiting when ammonia excess occurs in the presence of hepatic failure. In three of the inherited urea cycle disorders, ornithine insufficiency and ammonia excess also occur. These disorders are citrullinemia, argininosuccinic aciduria, and argininemia. In the presence of excessive lysine the availability of arginine is reduced and the formation of ornithine is decreased in the liver; urea synthesis is reduced, but orotic acid synthesis is increased, and orotic aciduria results as carbamyl phosphate is directed toward the pyrimidine pathway. Hereditary lysinuric protein intolerance results in ornithine depletion, hyperammonemia, and orotic acid uria. Optimal growth in several species of animals requires 0.4-1.0% arginine in the diet. Diets deficient in arginine are associated with poor wound healing as well as stunted growth. The measurement of orotic acid excretion has been a convenient indicator of insufficiency of ornithine or arginine during growth or pregnancy in animals and should prove useful in assessing the requirement for arginine after trauma. Normal human pregnancy is associated with low-grade orotic aciduria. Protein deficiency and malnutrition increase the vulnerability of the animal or child to ammonia toxicity. This is presumably due to insufficient ornithine for normal urea cycle responsiveness. PMID- 3088084 TI - Carnitine as an essential nutrient. AB - Carnitine performs a critically important role in energy metabolism and is synthesized in the healthy adult predominantly in the liver and kidney. The typical well balanced American diet contains significant amounts of carnitine as well as the essential amino acids and micronutrients needed for carnitine biosynthesis. Thus carnitine is an infrequent problem in the healthy, well nourished adult population in the United States. However, carnitine can be a conditionally essential nutrient for several different types of individuals. Preterm infants require carnitine for life-sustaining metabolic processes but have a carnitine biosynthetic capability that is not fully developed. There is an increasing number of documented problems with carnitine metabolism in preterm infants not receiving an exogenous source of carnitine indicating that endogenous biosynthesis of carnitine is not adequate to meet the infant's need. Children with different forms of organic aciduria appear to have a greatly increased need for carnitine to function in the excretion of the accumulating organic acids. This need exceeds their dietary carnitine intake and carnitine biosynthetic capability. Renal patients treated with chronic hemodialysis appear to lose carnitine via the hemodialysis treatment, and this loss cannot be repleted simply by endogenous biosynthesis and dietary intake. Treatment with drugs such as valproic acid and metabolic stresses such as trauma, sepsis, organ failure, etc, can also result in a requirement for exogenous carnitine. Accurate assessment of the carnitine status of patients at risk for carnitine deficiency is fundamental to the identification of those patients who require carnitine as the result of altered metabolism. PMID- 3088086 TI - Estimating prevalence of adverse reactions to foods: principles and constraints. AB - Future research in the area of adverse reactions to foods should use the basic principles of epidemiology to allow the prevalence of these adverse reactions to be established. The process of incorporating these principles into future research will aid in the identification of the etiology of adverse reactions through the clarification of definitions, refining of testing and assessment procedures for classifying reactions, and the identification of the populations who are indeed at risk for the numerous types of reactions that may occur. Although the evaluation of adverse reactions is a challenging problem, it is a problem that can be overcome. PMID- 3088085 TI - The impact of health education on frequency and cost of health care use by low income children with asthma. AB - A sample of 310 low income urban children with asthma from 290 families was randomized into a control group and an experimental group that received health education to improve asthma management at home. No significant decreases in subsequent health care use were observed when the experimental group was compared to the control group without regard to previous hospitalization. When the comparison was restricted to children who had been hospitalized during the preceding year, however, the experimental group was found to have decreased its use of the emergency room significantly more than the control group (p less than 0.05) and to have experienced a significantly greater reduction in the mean number of hospitalizations (p less than 0.05) during the year of follow-up. The program reduced health care costs for children with one or more hospitalizations, saving $11.22 for every $1.00 spent to deliver health education. PMID- 3088087 TI - Design of clinical trials. PMID- 3088088 TI - Impact of Medicare diagnosis-related groups (DRGs) on nursing homes in the Portland, Oregon metropolitan area. AB - To evaluate the impact of the Medicare Prospective Payment System (PPS) on nursing homes, resident census and staffing data from 78 Portland, Oregon nursing homes were compiled from annual reports filed with the state. Between fiscal years (FYs) 1983 and 1984, (before and after initiation of the Medicare PPS), there was no significant change in the total number of patient-days, but there was a 20.5% increase in the total number of deaths and a significant increase in average facility adjusted death rates (P = .004). Between the previous FYs 1982 and 1983, the total number of deaths had risen only 8.3%, and the average facility adjusted death rate had no significant change. Since initiation of diagnosis-related groups (DRGs), these nursing homes also made sizeable increases in their adjusted full-time registered nurse employment rate, and reported fewer patients reimbursed by Medicare. These same nursing homes were surveyed in spring, 1985 to determine the impact of Medicare DRGs in more qualitative terms. Of the 51 nursing homes (66%) responding, more than half reported increased severity of illness, shorter length of stay, increased prevalence of clinical problems, and increased use of medical supplies. In addition, more than half of the respondents reported increased frequency of requests for Friday and weekend admissions, admission of patients too sick for the facility, and physician phone consultation. These findings indicate that Portland, Oregon nursing homes experienced increased patient severity of illness, explained at least in part by earlier hospital discharge, following DRGs. PMID- 3088089 TI - Cognitive impairment. Can it predict the course of hospitalized patients? AB - All patients admitted to three medical services at the New York Hospital during a one-month period were screened with Folstein's Mini-Mental State Examination. The prevalence of cognitive impairment was 19.8% (23 of 116). Cognitively "impaired" patients, ie, those with a Folstein score less than 24, were older, sicker, and less physiologically stable than the cognitively "intact." The in-hospital mortality (17 versus 5%) and morbidity (39 versus 18%) rates were higher for the cognitively "impaired" patients; these differences could be explained by the greater severity of illness, instability, and comorbidity found in these patients. Cognitively "impaired" patients were particularly susceptible to respiratory complications. Cognitively "impaired" patients had longer lengths of hospital stay, spent more time in hospital awaiting placement, and were more likely to be discharged to a nursing home or require home assistance than their cognitively "intact" counterparts. Three-month mortality rates were also higher for the cognitively "impaired" patients (30 versus 15%). These findings suggest that cognitive impairment on admission may be regarded as a marker for patients with poorer prognoses. PMID- 3088091 TI - An analysis of congressional health policy voting in the 1970s. AB - This paper analyzes nine health policy votes in the U.S. House of Representatives. The votes all occurred between 1973 and 1980 and include such issues as health planning, health maintenance organizations, cost containment, and professional standards review organizations. The objective of this analysis is to examine the independent contribution of variables indigenous to health issues while controlling for party identification and ideology. The influence of health providers, measured by the effect of the number of state medical association members in each state, is significant in the findings. The state and local share of Medicaid expenses is also significant in explaining several votes. Contributions from political action committees were not important until 1979, when the rising costs of campaigns gave them more influence, and when our measures of their influence improved. By the time Congress voted in 1979 on hospital cost containment legislation, the PAC variable surpassed even the AMA variable in importance. PMID- 3088090 TI - Nurses' and physicians' attitudes toward tube-feeding decisions in long-term care. AB - We studied attitudes of health professionals toward life-sustaining treatment. A patient management questionnaire sent to staff physicians and nurses in 183 Oregon nursing homes consisted of eight patient sketches which varied age, mental status, and enjoyment of life. Respondents were asked whether they would favor tube-feeding to correct malnutrition in each case. Nurses showed higher preferences for tube-feeding than did physicians (P = .05). For both professions, patient happiness was the strongest and most significant (P less than .0001) influence upon preferences for tube-feeding. Both professions also showed a significant (P less than .001) tendency to give younger patients higher preferences for tube-feeding. Physicians showed a significant (P less than .001) influence of patient mental status upon preferences, while patient mental status did not affect nurses' preferences. Identifiable clinical factors appear to influence attitudes of physicians and nurses toward tube-feeding decisions. PMID- 3088092 TI - Per case prospective payment for psychiatric inpatients: an assessment and alternatives. AB - Psychiatric hospitals and clinics are exempted from the Medicare prospective payment system. In this paper we examine the appropriateness of the DRG classification system for psychiatric patients and argue that, using this system as the basis of payment, two types of problems are likely to arise. We categorize these problems as "risks to hospitals" and "risks to patients" and examine the existing literature to determine whether these risks are likely to be significant. We propose a different approach to paying prospectively for psychiatric care, and suggest modifications that could be made to the structure of PPS to mitigate negative incentives embedded in the current system. Although the main focus of the paper is on the unit of payment, we also make some observations about issues arising in connection with the level of payment. PMID- 3088093 TI - Systemic surgical shunts and splenomegaly as causes of haemolysis in portal hypertension in mansonic schistosomiasis. Evaluation through serum levels of haptoglobin, hemopexin and bilirubins. AB - The haemolytic process in hepatosplenic schistosomiasis is often regarded as a result of splenomegaly that can be increased by spontaneous or surgical shunts. The importance of splenomegaly and/or shunt on the etiology of haemolysis was studied in a group of 74 patients with hepatosplenic schistosomiasis and portal hypertension. They were divided into 4 groups: Group I (22 cases) - pre operative; Group II (15 cases) - classic splenorenal shunt; Group III (22 cases) selective portal decompression and Group IV (15 cases) - azygoportal disconnection with splenectomy. The first group is characterized by the presence of splenomegaly and the absence of shunt; the second by the presence of shunt and absence of splenomegaly; the third, by the presence of both splenomegaly and shunt and the last by absence of both, shunt and splenomegaly. In all cases, the levels of sensitive markers of haemolysis, such as haptoglobin and hemopexin as well as non-conjugated and total bilirubins were determined. Biochemical and coagulation parameters, used to evaluate the hepatic function, were also studied. The data was initially analysed according to a factorial experiment of 2 and standard least squares techniques were used to evaluate the effects of splenomegaly, shunt and their interaction. The results showed that the shunts always provoked haemolysis, even in the absence of splenomegaly, but the presence of both, splenomegaly and shunt, always increased the process of haemolysis. PMID- 3088094 TI - Search for hepatitis B virus DNA in sera from patients with acute type B or non A, non-B hepatitis. AB - One hundred and three single sera from adults hospitalized with acute type B (78) or non-A, non-B (25) hepatitis were tested for the presence of hepatitis B virus DNA (HBV DNA). All sera from patients with type B hepatitis were IgM anti-HBc positive. These patients were classified as benign (47) or fulminant (31) hepatitis. The 25 acute non-A, non-B patients were also classified as benign (21) or fulminant (4) hepatitis and were negative for serologic markers of past HBV infection. Serum HBV DNA was detected with similar frequency in benign (38.5%) and fulminant (FH, 34.6%) HBsAg-positive cases. HBV DNA was not detected in either the 26 acute HBsAg-negative hepatitis B cases who were positive for anti HBc and anti-HBs or the 25 acute non-A, non-B hepatitis cases. The absence of HBV DNA in 43.8% of benign hepatitis B patients who were positive for HBsAg and HBeAg could possibly be attributed to either low level replication of HBV that was not detectable by the [32P]HBV DNA probe or to a period of delayed clearance of free HBeAg following cessation of HBV replication. Emergence of anti-HBs in the presence of HBsAg did not always correspond to clearance of HBV in fulminant type B cases. However, in acute type B hepatitis, irrespectively of severity, disappearance of HBsAg and appearance of anti-HBs was accompanied by reduction of HBV replication to undetectable levels. PMID- 3088096 TI - Management of the acutely ill diabetic patient. PMID- 3088095 TI - Mouthcare and the intubated patient--the aim of preventing infection. PMID- 3088097 TI - Ketoacidosis in the diabetic child: a metabolic emergency. PMID- 3088098 TI - Evaluation of patients with intractable seizures for epilepsy surgery at Indiana University Medical Center. PMID- 3088099 TI - Is Medicare bankrupt? PMID- 3088101 TI - Studies on the role of antigen-presenting cells in the systemic suppression of contact hypersensitivity by UVB radiation. AB - Exposure of mice to UVB radiation produces a highly selective, systemic immunosuppression associated with the appearance of suppressor T lymphocytes. Suppression of delayed hypersensitivity to hapten-coupled syngeneic cells has been shown to result from an altered distribution of antigen-presenting cells. The purpose of this study was to determine whether an alteration in the activity of antigen-presenting cells could account for the systemic suppression of contact hypersensitivity (CHS) by UVB radiation. Fluorescein isothiocyanate (FITC) was used for contact sensitization because it uses different antigen-presenting cells than does oxazolone to induce CHS. Our previous studies demonstrated that CHS to oxazolone was suppressed by UVB irradiation. In these studies, we show that exposure of mice to UVB radiation before epicutaneous application of FITC onto unirradiated skin markedly decreased the CHS response to FITC painted on unexposed ears. Cyclophosphamide-sensitive suppressor T cells were detectable in the spleens of mice exhibiting decreased CHS. The antigen-presenting activity of cells in lymph nodes draining the site of epicutaneous sensitization (DLN cells) was assessed by injecting them into the hind footpads of syngeneic recipients and measuring the CHS response to FITC 6 days later. Viable DLN cells from UVB irradiated, FITC-sensitized mice were equal to those from unirradiated, FITC sensitized mice in their ability to induce CHS in normal recipients. No sensitization resulted when killed DLN cells were used for immunization, indicating that sensitization was not caused by reprocessing of antigen by host cells. We conclude that impairment of the CHS reaction in UVB-irradiated mice does not appear to be blocked at an initial step of antigen uptake, processing, or presentation, but must be impaired at some other step in the immunologic pathway. PMID- 3088100 TI - Species-restricted recognition of transfected HLA-A2 and HLA-B7 by human CTL clones. AB - Human cytolytic T lymphocytes (CTL) clones and HLA-A2- and HLA-B7-transfected human, monkey, and mouse cell lines were used to investigate the basis for species-restricted antigen recognition. Most allospecific CTL clones obtained after stimulation with the human JY cell line (source of HLA-A2 and HLA-B7 genomic clones) recognized HLA antigens expressed in human and monkey cell lines but did not recognize HLA expressed in murine cells. By initially stimulating the responder cells with HLA-transfected mouse cells, two CTL clones were obtained that recognized HLA expressed in murine cells. Functional inhibition of these CTL clones with anti-class I monoclonal antibodies (MAb) indicated that clones reactive with HLA+ murine cells were of higher avidity than clones that did not recognize HLA+ murine target cells. MAb inhibition of accessory molecule interactions demonstrated that the LFA-1 and T8 surface molecules were involved in CTL-target cell interactions in all three species. In contrast, the LFA-2/CD2 molecule, previously shown to participate in a distinct activation pathway, was involved in the cytolysis of transfected human and monkey target cells, but not in the lysis of HLA+ murine cells. Thus transfection of HLA genes into different recipient species cell lines provides us with the ability to additionally delineate the functional requirements for allospecific CTL recognition and lysis. PMID- 3088102 TI - All human monocytes have the capability of expressing HLA-DQ and HLA-DP molecules upon stimulation with interferon-gamma. AB - We have simultaneously studied expression of all three classes of human Ia (HLA DR, DP, and DQ) on normal human B cells and monocytes (M phi) by using two-color immunofluorescence and flow cytometry. Expression was investigated on freshly isolated cells and after incubation of cells for 48 and 96 hr in interferon-gamma (IFN-gamma). All freshly isolated B cells express high levels of DR, DQ, and DP, and these levels are unchanged by incubation with IFN-gamma for 48 hr and 96 hr. In contrast, freshly isolated M phi are on the average 91% DR+, 32% DQ+, and 15% DP+. Incubation with IFN-gamma increases Ia expression on M phi to 98% DR+, 75% DQ+, and 58% DP+ at 48 hr, with virtually all cells becoming positive for all three Ia antigens at 96 hr. Furthermore, after the 96-hr incubation, antigen density increases 10-fold for DR, 15-fold for DQ, and 15-fold for DP in M phi to reach levels of expression comparable with B cells. These studies demonstrate that all peripheral blood monocytes have the capacity to become HLA-DQ and HLA-DP positive; IFN-gamma regulates expression of all three classes of human Ia in M phi; and IFN-gamma does not significantly modulate Ia expression in B cells. PMID- 3088103 TI - Identification of a human monocyte cytotoxicity-inducing factor from T cell hybridomas produced from Sezary's cells. AB - Sezary's syndrome is a leukemic proliferation of OKT4+ lymphocytes. Sezary cells were isolated by differential centrifugation and fused to CEM.8azar.C, and HGPRTase-lacking clone of CEM. The hybrid cells were studied for their ability to produce soluble mediators of human monocyte cytotoxicity. The product of a single clone, FtF3, which bore the surface phenotype of Sezary cells, was characterized. Monocyte cytotoxicity-inducing factor (MCF) was found to be stable at pH 2 for 1 hr, unlike IFN-gamma, and was found to be more heat stable as well. Moreover, treatment of MCF with antisera to IFN-gamma, IFN-alpha or a combination of IFN gamma and IFN-alpha failed to neutralize its biologic activity. MCF binds to matrix gel Red A. MCF eluted from this dye-ligand was found to have an apparent m.w. of 11,500 by gel filtration and 14,700 by SDS-polyacrylamide gel electrophoresis. MCF produced by hybridized Sezary cells appear to be neither IFN gamma nor an altered molecular form of IFN-gamma, yet is a potent inducer of human monocyte cytotoxicity. PMID- 3088104 TI - T cell replacing factor for steroids (TRF-S): a 40,000 dalton protein produced by a T4+ T cell. AB - The induction of polyclonal immunoglobulin (Ig) synthesis by glucocorticosteroids (GCS) in human peripheral blood lymphocytes is dependent on both T cells and monocytes. T cells can be replaced by a cytokine, T cell replacing factor for steroids (TRF-S), which promotes GCS-induced Ig production. T cells produce the cytokine when cultured with intact monocytes, with 24 hr monocyte supernatants, or with small quantities (0.1 U/ml or more) of highly purified interleukin 1 (IL 1). TRF-S was produced by isolated T4+ cells, whereas isolated T8+ cells were unable to help GCS-induced Ig synthesis. High pressure liquid chromatography with a gel permeation column revealed a single locus of activity that corresponded to an apparent m.w. of 40,000. At the dilutions utilized in culture, supernatants containing optimal TRF-S activity (3 U/ml final concentration in culture) were found to have less than 0.2 U/ml (final concentration) of interleukin 2 (IL 2) activity. Neither recombinant IL 2 nor recombinant interferon-gamma (IFN-gamma) over a broad range of concentrations was able to reproduce the capacity of TRF-S to induce the development of Ig-secreting cells with GCS. Thus, we report that TRF-S is synthesized primarily by T4+ T cells, and that its production is stimulated by small concentrations of IL 1. The apparent m.w. of TRF-S is 40,000, and its biological activity is distinct from that of IL 1, IL 2, and IFN-gamma. PMID- 3088105 TI - Regulation of the BALB/c anti-p-azophenylarsonate antibody response by monoclonal anti-idiotype. I. Anti-idiotope fine specificity. AB - Five monoclonal anti-idiotype antibodies were prepared against the IgG1 monoclonal antibody, 5AF6, the prototype molecule representing the BALB/c 5AF6 idiotype family of antibodies specific for the p-azophenylarsonate (Ar) hapten. Three were of BALB/c origin and two were derived from allotype congenic strain CB.20. All five anti-idiotopes (id) reacted with the 5AF6 immunogen but not with four other BALB/c anti-Ar sharing other id with 5AF6. Four of the five showed some reactivity with three monoclonal anti-Ar derived from A strain mice that represent a minor component of the anti-Ar from that strain. Reactivity patterns of these anti-id indicated that all five reacted with different id on the 5AF6 molecule, yet all five were sufficiently close to the Ar-binding site for their binding to be blocked by the Ar hapten alone. Furthermore, all five anti-id could compete with each other for binding to 5AF6, indicating that the five id detected by these anti-id were in close proximity. Four of the five anti-id reacted with id produced by conformations requiring both the appropriate heavy and light chains. The fifth anti-id reacted with a heavy chain id stabilized by the presence of any light chain. The implications of such a diverse anti-id response against a single antibody molecule on anti-id network interactions are discussed. PMID- 3088106 TI - Oxygen-independent inhibition of intracellular Chlamydia psittaci growth by human monocytes and interferon-gamma-activated macrophages. AB - We have demonstrated previously that Chlamydia psittaci grows well in human monocyte-derived macrophages, but to a limited extent in lymphokine-or interferon gamma (IFN-gamma)-activated macrophages. In this investigation, freshly explanted human monocytes inhibited chlamydial inclusion formation by 85% as compared to macrophages, and the level of inhibition was similar to that exhibited by lymphokine-activated macrophages (79%). To determine whether the oxygen-dependent antimicrobial mechanisms of the mononuclear phagocyte were involved in the inhibition, cells were infected with C. psittaci in the presence of agents that either inhibit the respiratory burst (glucose deprivation) or diminish the effect of H2O2 (catalase). These treatments had no effect on the capacity of monocytes and lymphokine-activated macrophages to restrict chlamydial growth. In addition, monocytes and activated macrophages from an individual with chronic granulomatous disease suppressed chlamydial growth as effectively as normal cells. Oxidatively deficient HeLa and endothelial cells, once stimulated by lymphokine, also displayed normal levels of antichlamydial activity. The induction of this apparently oxygen-independent antichlamydial effect by lymphokine was completely neutralized by a monoclonal anti-IFN-gamma antibody, and could be achieved by treatment with recombinant (r)IFN-gamma alone. These results indicate that the primary antimicrobial mechanism of the human monocyte against C. psittaci is oxygen-independent, and that this response can be effectively stimulated in the macrophage by lymphokine (IFN-gamma). PMID- 3088107 TI - A genetically engineered murine/human chimeric antibody retains specificity for human tumor-associated antigen. AB - Chimeric immunoglobulin genes were constructed by fusing murine variable region exons to human constant region exons. The ultimate goal was to produce an antibody capable of escaping surveillance by the human immune system while retaining the tumor specificity of a murine monoclonal. The murine variable regions were isolated from the functionally expressed kappa and gamma 1 immunoglobulin genes of the murine hybridoma cell line B6.2, the secreted monoclonal antibody of which reacts with a surface antigen from human breast, lung, and colon carcinomas. The kappa and gamma 1 chain fusion genes were co introduced into non-antibody producing murine myeloma cells by electroporation. Transfectants that produced murine/human chimeric antibody were obtained at high frequency as indicated by immunoblots probed with an antisera specific for human immunoglobulin. Enzyme-linked immunoabsorbent assay analysis demonstrated that this chimeric antibody was secreted from the myeloma cells and retained the ability to bind selectively to membrane prepared from human tumor cells. The chimeric immunoglobulin was also shown by indirect fluorescence microscopy to bind to intact human carcinoma cells with specificity expected of B6.2. The ability of chimeric antibody to recognize human tumor-associated antigen makes feasible a novel approach to cancer immunotherapy. PMID- 3088108 TI - Role for carbohydrate moieties in immune response to malaria. PMID- 3088109 TI - The role of the accessory cell in mitogen-stimulated human T cell gene expression. AB - The role of the accessory cell in optimizing T cell proliferative responses to mitogens is a well known but poorly understood phenomenon. To further dissect the function of the accessory cell in allowing T cell proliferation, we compared mitogen-induced c-myc, interleukin 2 (IL 2), and IL 2 receptor gene expression in peripheral blood mononuclear cells (PBMC) and in T cells rigorously depleted of accessory cells through differential adherence and anti-Dr (anti-class II major histocompatibility antigen) monoclonal antibody complement-directed cytotoxicity. In cultures stimulated with phytohemagglutinin (PHA), a mitogen that requires accessory cells to induce T cell proliferation, expression of all measured genes was accessory cell dependent, since accumulation of their mRNA in PBMC was greater than that in cultures depleted of accessory cells. These genes varied in their accessory cell dependence, with IL 2 expression most dependent, c-myc expression least dependent, and IL 2 receptor expression intermediate in dependency. Use of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or ionomycin, mitogens that stimulate T cell proliferation independent of accessory cells, induced equal levels of gene expression in PBMC and in T cells depleted of accessory cells. These results suggest that PHA-stimulated T cells are dependent on an accessory cell signal(s) for optimal expression of the genes for c-myc, IL 2, and IL 2 receptor, and for proliferation. In addition, this signal(s) appears to be delivered early in the course of T cell activation events, since it can be bypassed by mitogens that directly activate protein kinase C (TPA) or induce calcium translocation (ionomycin). In addition, these data provide further evidence that expression of the c-myc protooncogene is insufficient for T cell mitogenesis, since PHA-induced accumulation of c-myc mRNA was only partially accessory cell dependent, whereas proliferation was completely accessory-cell dependent. PMID- 3088110 TI - Differential induction of H-2K vs H-2D class I major histocompatibility complex antigen expression by murine recombinant interferon-gamma. AB - The results presented here indicate that recombinant murine interferon-gamma can cause a dramatic differential induction of two distinct class I MHC molecules. Thus, IFN-gamma treatment of the murine leukemia virus (MuLV)-induced AKR SL3 tumor, a cell line that normally expresses moderate levels of class I MHC antigens, resulted in a large increase in H-2Dk expression, but no change or a slight decrease in H-2Kk expression as measured by cytofluorography. Explanations of the selective enhancement of Dk expression based on increased Fc receptor display or differential kinetics of induction were ruled out. The phenomenon was observed over a wide range of doses of IFN-gamma and with two different monoclonal antibodies to Kk, the latter finding making it unlikely that an altered form of the Kk molecule was induced. The same differential induction of the Dk antigen was observed for the LBRM.5A4 tumor cell line. Because LBRM.5A4 is also MuLV+ but of congenic B10.BR (H-2k) origin, these results were consistent with the possibility that such differential induction was associated with the H 2k haplotype and/or MuLV. The implications of these results, as a possible mechanism of tumor cell escape from an immune surveillance system monitored by class I MHC-restricted T cells and as a useful model system to dissect the mechanism of IFN-gamma induction of class I MHC antigens, are discussed. PMID- 3088111 TI - Synergy between the T3/antigen receptor complex and Tp44 in the activation of human T cells. AB - In addition to the T3/antigen receptor complex (T3/Ti), other T cell surface molecules participate in early events involved in human T cell activation. In this report we document that monoclonal antibody 9.3, which recognizes a 90,000 dalton homodimer expressed on human T cells, synergizes with ligands reacting with T3/Ti to activate purified T cells and Jurkat, a human T cell leukemic line. Unlike phorbol myristate acetate (PMA), 9.3 was able to synergize only with anti T3 or anti-Ti if these antibodies were immobilized. Moreover, 9.3 failed to synergize with the calcium ionophore ionomycin. At high concentrations only, 9.3 could synergize with PMA in the activation of Jurkat and a T3/Ti negative mutant of Jurkat. At such high concentrations of 9.3, small transient increases in cytoplasmic free calcium ((Ca++)i) were detected in quin 2-loaded Jurkat cells. This increase in (Ca++)i was the result of release of internal stores of calcium. 9.3 induced the hydrolysis of polyphosphoinositides, albeit the magnitude of inositol phosphates generated in response to 9.3 was substantially less than that observed with anti-Ti. No effect on pkC translocation was observed in Jurkat cells stimulated with 9.3. Although the small increase in (Ca++)i induced by 9.3 may account for its synergy with PMA, this effect is unlikely to account for the more potent synergistic effect observed with 9.3 and phytohemagglutinin or immobilized anti-T3 and anti-Ti antibodies. PMID- 3088112 TI - Purification to homogeneity of a human hematopoietic growth factor that stimulates the growth of a murine interleukin 3-dependent cell line. AB - A human lymphokine derived from the 5637 bladder carcinoma has been purified to homogeneity by using sequential reverse-phase high pressure liquid chromatography. A high recovery of biological activity is obtained by using this purification. The NH2-terminal amino acid sequence shows no homology to human interleukin 1 (IL 1), human IL 2, murine IL 3, or human granulocyte-macrophage colony-stimulating factor. The growth-promoting properties of the 5637-derived factor can be rapidly assayed by using the murine IL 3-dependent 32D c1-23 cell line. The amino acid sequence described is identical to that recently described for a human granulocyte colony-stimulating factor. PMID- 3088113 TI - Suppression of immune responses to sheep erythrocytes by the lymphokine soluble immune response suppressor (SIRS) in vivo. AB - Soluble immune response suppressor (SIRS) is a protein produced by activated suppressor T lymphocytes which inhibits division by tumor cells and plaque forming cell (PFC) responses in vitro. Although this lymphokine has been fairly well characterized in vitro, little is known about its effects in vivo. Purified murine SIRS, 10(3) to 10(4) U injected i.p., suppressed murine PFC responses to sheep erythrocytes (SRBC) in vivo. Suppression occurred when SIRS was injected into mice 5 days before assay, and also occurred when SIRS activated with 10(-6) M H2O2 was injected 24 hr before assay. These kinetics are similar to those observed in tissue culture, where suppression of PFC responses requires the addition of SIRS 4 to 5 days before assay unless SIRS is activated to SIRSox by H2O2. Levamisole, an inhibitor of SIRS-mediated suppression in vitro, also blocked suppression by SIRS in vivo. Delayed-type hypersensitivity reaction to footpad injection of SRBC was also inhibited by SIRS. Suppression of PFC responses by recombinant immune interferon (IFN-gamma), which activates lymphocytes to produce SIRS in vitro, was blocked by injection of levamisole or monoclonal anti-SIRS antibodies. These results show that SIRS suppresses immune responses in vivo, and suggest that suppression of PFC responses by IFN-gamma may be largely mediated by SIRS. These findings indicate that SIRS could contribute to the development of suppressed immunity in vivo. PMID- 3088114 TI - Lymphokine stimulation of human macrophage C2 production is partially due to interferon-gamma. AB - Monocyte complement stimulator (MCS), a product of T lymphocytes, is defined by its ability to stimulate the synthesis and secretion of the second complement component (C2) by monocytes. Most macrophage-activating factor (MAF) activity present in lymphokine-rich culture supernatants has recently been found to be due to interferon-gamma (IFN-gamma). We therefore hypothesized that IFN-gamma may have MCS activity as well. We tested recombinant, E. coli-derived, human IFN gamma (rIFN-gamma) for its effects on C2 production by adherent peripheral blood monocytes and U937 cells, a human monocytic cell line. Recombinant IFN-gamma in concentrations ranging from 0.1 to 300 U/ml (0.003 to 8.8 ng/ml) stimulates C2 production by both cell populations. Exposure of responding cells for at least 24 hr is required for maximal stimulation. To determine the contribution of IFN gamma toward total MCS activity in crude lymphokine-rich supernatants, we employed a solid-phase immunoabsorption technique with the use of a monoclonal anti-IFN-gamma antibody. This technique removed all IFN-gamma detectable by a sensitive ELISA, but MCS activity was decreased by only 40 to 50%. Additionally, MCS activity of these supernatants did not correlate with IFN-gamma content as determined by ELISA. By using another method to eliminate IFN-gamma activity, acid dialysis destroyed all rIFN-gamma activity, as measured by stimulation of U937 C2 synthesis, but eliminated only 30 to 67% of MCS activity from crude lymphokine preparations. Thus IFN-gamma stimulates C2 production by monocytes and U937 cells and apparently accounts for some, but not all, MCS activity present in lymphokine-rich supernatants. Other lymphokines are present in such supernatants that also possess this activity. PMID- 3088115 TI - Phagocytosis by human monocytes of unopsonized particulate activators of the human alternative complement pathway: induction by cytokine. AB - Monocytes isolated from human blood by centrifugal elutriation exhibited little ability to ingest rabbit erythrocytes (ER), zymosan particles, or desialated sheep erythrocytes. In contrast, 85 to 95% of these cells rosetted with C3b- or C3bi-bearing sheep erythrocytes (ES) or ingested IgG-coated ES. Preincubation of the monocytes with human lymphocytes increased their ability to ingest ER. the ER phagocytosis-inducing activity was contained in the 105,000 X G supernatant of lymphocyte lysates. These supernatants increased the percentage of ingesting monocytes from 5 to 15% to 80% within 60 min. The soluble factor was found to be relatively heat stable, inactivated by trypsin, and distinct from IFN-gamma. Its m.w. is less than 13,000. It was present in B and T lymphocytes and also in U937 cells. These results suggest that the ability of human monocytes to ingest nonopsonized particulate activators of the alternative complement pathway is a cytokine-inducible property and that the effect of the cytokine on complement receptor- or Fc receptor-dependent adherence or ingestion of opsonized particles is minor. PMID- 3088116 TI - Genetic basis for altered idiotype expression in the hyperimmune response to (4 hydroxy-3-nitrophenyl)acetyl hapten. AB - To assess the significance of somatic point mutation in the hyperimmune response to the hapten NP, an in vivo enrichment procedure was followed. Mice that expressed high titers of B1-8 idiotopic determinants were selected as donors for serial transfer of small numbers of immune spleen cells into syngeneic irradiated recipient mice. Cells expressing B1-8 idiotopic determinants were chosen for enrichment because B1-8 cross-reactive determinants constitute a significant portion of the primary response. Furthermore, B1-8 is a monoclonal antibody derived from a primary response to NP, and its heavy and light chains are unmutated products of the germ-line genes VH186.2 and VL lambda 1, respectively. The germ-line sequence is thus available for comparison with the somatic mutants that arise during enrichment and hyperimmunization. The data show that serial transfer of spleen cells from mice with a high titer of idiotypic determinants results in a dramatic decrease in the titers of antibodies that bind antigen. Three lines of evidence indicate that progeny cells from the initial lambda positive, idiotype-bearing, antigen-binding cells are successfully transferred and expanded during successive adoptive transfers. First, the proportion of lambda-bearing antibodies relative to NP-specific lambda-bearing antibodies increases with transfer, which is consistent with mutation away from antigen binding. Second, analysis of serum antibodies and hybridoma proteins derived from transfer-recipient mice confirm the presence of idiotype-positive antibodies that do not bind antigen. Third, RNA dot blot analysis of hybridomas constructed from a recipient mouse in the fourth transfer indicates a high frequency of expression of the VH gene predominantly used in the NP response. Many of the antibodies expressed by these hybridomas not only do not bind antigen, but have also lost the determinants recognized by the anti-idiotypic reagents. Most of these VH positive hybridomas express lambda L chain. The most likely interpretation of the data is that somatic mutation is occurring during the hyperimmune response. Because we selected donor mice that expressed a high titer of idiotype-positive, antigen-specific antibody and immunized the recipient mice, we expected to observe a selective expansion of somatic variants that bound antigen. This was not the case. The observed loss of antigen binding suggests that the majority of mutations arising result in antibodies with lower affinity for the immunizing antigen. PMID- 3088118 TI - Isolation of pure functionally active CD8+ T cells. Positive selection with monoclonal antibodies directly conjugated to monosized magnetic microspheres. AB - A monoclonal antibody of the IgM isotype, ITI-5C2, which binds with high affinity to CD8 molecules, was directly conjugated to the monosized magnetic microspheres M-450. This permits selective removal of the CD8+ T cell subset (T8) from peripheral blood mononuclear cell suspensions in a rapid one-step procedure. With a low ratio of microspheres to cells (2:1), functionally active T8 cells can be recovered. In vitro experiments involving such positively selected T8 cells or recombinations of isolated T8 and T4 subsets, demonstrate that the presence of M 450 microspheres coated with ITI-5C2 do not interfere with the immunological functions of the positively selected cells. The method has possible application in the isolation of all cell populations where high avidity mAbs of appropriate specificity are available. PMID- 3088117 TI - Effect of recombinant interferon-gamma on hydrogen peroxide-releasing capacity of monocyte-derived macrophages from patients with lepromatous leprosy. AB - Monocyte-derived macrophages from 14 patients with lepromatous leprosy respond to rIFN-gamma with an enhanced secretion of H2O2 in a fashion similar to that of cells obtained from normal donors. The activation is not dependent on the cutaneous bacterial index, the length of treatment, or the stage and activity of the disease. H2O2 release can be triggered in these cells both by phorbol myristate acetate and by intact irradiated Mycobacterium leprae. Uptake of M. leprae by both normal donors' and patients' macrophages is proportional to the number of bacilli added. Prior ingestion of M. leprae does not interfere with the ability of macrophages to respond to IFN-gamma by the production of oxygen intermediates. We conclude that the immune defect in lepromatous leprosy probably results from a lack of response to M. leprae by the patients' T cells rather than an inability of mononuclear phagocytes to respond to IFN-gamma. PMID- 3088119 TI - Human T lymphocyte clones with killer or natural killer activity. AB - We describe a reliable method for obtaining a significantly higher frequency of human cloned T lymphocytes with killer and/or NK-like activity. Human peripheral blood mononuclear cells were treated with recombinant interferon-gamma (rIFN gamma) and recombinant interleukin-2 (rIL-2) in a culture medium containing autologous serum and were then cloned by single cell micromanipulation. The cloned T lymphocyte populations were tested simultaneously for their ability to proliferate in response to exogenous IL-2, to exhibit lectin-dependent cytolysis and to kill the tumor cell line K562. Results indicate that the cloning technique allowed each isolated T lymphocyte to undergo cell expansion. Furthermore when T cells were pretreated with rIFN-gamma and rIL-2, 88% of the T cell clones were capable of mediating cytotoxicity in the presence of PHA. Moreover one third of the clones which exhibited lectin-dependent lysis were able to kill K562 target cells. PMID- 3088120 TI - Quantitation of monoclonal immunoglobulins by immuno-isoelectric focusing and its application for monitoring secretory B cell neoplasia. AB - A scheme for quantitation of serum and urinary paraproteins is described using isoelectric focusing and scanning densitometry. Paraproteins could be quantified using this system when present at concentrations ranging from 1 mg/ml to 26 mg/ml, depending on the immunoglobulin class. The relevance of these results to monitoring secretory B cell neoplasia and the distinction between monoclonal gammopathy of undetermined significance and myeloma is discussed. PMID- 3088121 TI - Cryopreservation of human lymphocytes for assessment of lymphocyte subsets and natural killer cytotoxicity. AB - Cryopreservation of lymphocytes has become increasingly important, especially when the cells are to be used in retrospective studies of selected and dwindling populations, such as A-bomb survivors. This report describes an efficient method for cryopreservation of human lymphocytes which does not significantly alter various immunological characteristics of these cells. The proportions of Leu-1+ cells (T cells), Leu-2a+ cells (suppressor-cytotoxic T cells), Leu-3a+ cells (helper-inducer T cells), HLA-DR+ cells, Mo2+ cells (monocytes), B1+ cells (B cells), and Leu-7+ cells (natural killer (NK) cells), as determined by monoclonal antibodies, were found to be stable following cryopreservation. NK cell activity against K-562 target cells showed a 40-60% decrease immediately after thawing, but recovered to approximate pre-freezing levels after preincubation for 18 h. Neither lymphocyte subsets nor cell viability significantly changed following preincubation after cryopreservation. However, the ratio of cells binding to K 562 cells increased after this preincubation and may account for the observed recovery of NK cell activity. NK cell activity remained relatively stable up to 14 months of storage which confirms that freezing damage depends on the freezing process rather than on the duration of cryopreservation. PMID- 3088122 TI - Identification of proliferating lymphocyte subpopulations by combined alkaline phosphatase anti-alkaline phosphatase (APAAP) staining and autoradiography. AB - An improvement in the classification of proliferating ([3H]thymidine incorporating) lymphocyte subpopulations in mitogen- or antigen-stimulated microcultures is described. The binding of subset-specific monoclonal antibodies is detected by the alkaline phosphatase anti-alkaline phosphatase method (APAAP). There are two advantages compared to the peroxidase anti-peroxidase (PAP) method; (1) endogenous enzyme (peroxidase) activity exhibited by some cells causes no interference, and (2) the red alkaline phosphatase staining obtained with new fuchsin provides a far superior contrast to silver grains than conventional peroxidase staining. PMID- 3088124 TI - Intestinal epithelial cells rosette with sheep red blood cells. AB - A large fraction of colonic epithelial cells (45 +/- 15%) formed rosettes with sheep red blood cells (RBC) but not with bovine or human RBC. This interaction was independent of the T11 receptor since it was not inhibited by anti-T11 antibody or trypsin treatment of the epithelial cells. The binding was also not due to surface immunoglobulin reactive with sheep RBC since antibodies to immunoglobulin light chains did not block the interaction. Sheep RBC rosettes formed around colonic and jejunal epithelial cells, a few percent of colonic adenocarcinoma cells, but not around uterine epithelial cells. Sheep RBC rosette formation should not be used to quantitate or isolate intestinal mucosal T cells if epithelial cells are present. PMID- 3088123 TI - Positive selection of viable cell populations using avidin-biotin immunoadsorption. AB - We have developed a new method for the selective enrichment of lymphoid subpopulations from dog and human bone marrow and peripheral blood. A mononuclear cell preparation was treated successively with monoclonal antibody, biotinylated goat anti-mouse immunoglobulin and passed over a column containing avidin linked to polyacrylamide or Sepharose beads. Adherent cells were recovered by mechanical agitation and analyzed by immunofluorescence staining and fluorescence-activated cell sorter analysis. Dog bone marrow mononuclear cells were treated successively with the antibody 7.2, which recognizes the Ia-antigen, 1:500 dilution of biotinylated goat anti-mouse immunoglobulin and passed over avidin-Biogel (1 mg/ml) at a flow rate of 3.0 ml/min. Enrichment from a starting population that was 24.4 +/- 9.1% 7.2-positive to 78.3 +/- 6.8% 7.2-positive adherent cell population was observed with 47.7 +/- 7.8% recovery of 7.2-positive cells. Human bone marrow mononuclear cells were treated successively with the T cell antibody Leu-4 followed by 1:500 dilution of B-GAMIg and passed over a column of avidin Biogel (1 mg/ml) at a flow rate of 1.5 ml/min. Enrichment from 7.2 +/- 3.3% Leu-4 positive cells in the starting cell population to 73.1 +/- 6.8% Leu-4-positive cells in the adherent cell population with total recovery of Leu-4-positive cells averaging 64.0 +/- 12.7%. Human bone marrow mononuclear cells positively selected with antibody Leu-4 or another T cell antibody, Leu-5 had a markedly enhanced response to the T cell mitogen, phytohemagglutinin compared to untreated bone marrow. Enrichment of a subpopulation of lymphocytes from dog peripheral blood mononuclear cells has been accomplished using antibody DT2, which reacts with a broad spectrum of dog lymphocytes. Nonspecific cell binding is primarily limited to granulocytes and monocytes. Future work is being directed at improving recovery of positively selected cells, reducing nonspecific cell binding and applying the technique to the selective enrichment of hematopoietic stem cells from bone marrow. PMID- 3088125 TI - Antibodies to La, Jo-1, nRNP and Sm detected by multi-track immunoblotting using a novel filter holder: a comparative study with counterimmunoelectrophoresis and immunodiffusion using sera from patients with systemic lupus erythematosus and Sjogren's syndrome. AB - The use of Western blotting or immunoblotting to detect autoantibodies in the serum of patients with autoimmune connective tissue diseases was investigated. An apparatus suitable for simultaneously screening 16 sera on immunoblots was used to show that a complex pattern of antibody binding polypeptides was present in whole HeLa cells. A simpler and readily interpreted pattern of binding was achieved using affinity-purified rabbit thymus antigens. Seventy-seven patients with systemic lupus erythematosus, 44 with primary Sjogren's syndrome and 50 normals were screened for anti-Sm, anti-La, anti-nRNP and anti-Jo-1 by immunoblotting and the results compared with those obtained by counterimmunoelectrophoresis and immunodiffusion. It was shown that both IgG and IgM antibodies must be analysed on immunoblots to detect the maximum number of positive sera, and that the immunoblot detects many anti-La sera which do not form precipitins. PMID- 3088126 TI - Adherent spleen cell production of E series prostaglandins in rats bearing variants of the R3327 Dunning prostatic adenocarcinoma: effect of cyclophosphamide. AB - Prostaglandins of the E series (PGE) have been implicated in many facets of immunoregulation, as well as having a possible role in metastatic dissemination. Variant sublines of the Dunning R3327 rat prostatic adenocarcinoma, differing in growth rate, hormonal responsiveness and in propensity for metastasis, were carried in Fisher X Copenhagen F1 animals. Adherent spleen cells were assayed in vitro for their ability to convert arachidonic acid to prostaglandins of the E series. These glass adherent cells presumably include the monocytic and T cell populations which have been implicated as being immunoregulatory. The results indicated that those spleen cells obtained from animals carrying the metastatic R3327-MAT-LyLu subline tumor converted more arachidonic acid to PGE's than cells derived from animals bearing non-metastatic sublines. Cyclophosphamide therapy did not alter such conversion. Multiple regulatory mechanisms for prostaglandin metabolism are suggested. PMID- 3088128 TI - Selection for increased resistance to aflatoxin B1 toxicity in Drosophila melanogaster. PMID- 3088127 TI - Stimulation of arachidonic acid release and eicosanoid biosynthesis in an interleukin 2-dependent T cell line. AB - Previous studies have provided pharmacologic evidence that T lymphocyte function may be regulated in part by the intracellular production of various arachidonic acid (AA) metabolites in response to cellular stimulation. However, the specific AA metabolic capabilities of homogeneous T cell populations have not been clearly defined. In the present studies, we have employed an accessory cell-free T cell line, HT-2, as a model system for the examination of stimulus-induced eicosanoid biosynthesis in T lymphocytes. HT-2 cells were biosynthetically labeled with [3H] AA and challenged briefly with various agents that stimulate the hydrolytic release of AA from cellular phospholipids. The bee venom peptide melittin stimulated a profound AA release response in the cells and the concomitant synthesis of both cyclooxygenase (PGF2 alpha, PGE2 and PGD2) and lipoxygenase (5 ,12-,15-HETE and possibly 5-,12-diHETE) metabolites of AA. The formation of PGs was blocked by 5 microM indomethacin, demonstrating that this cell line contains cyclooxygenase activity functionally similar to that described in macrophages and other cell types. The high activity of melittin in this system was shown to result largely from a synergy between the peptide itself and a persistent bee venom phospholipase A2 contaminant. However, experiments with melittin freed of detectable phospholipase A2 activity by heating, and with synthetic homopolymers of (L)-lysine and (L)-arginine demonstrated that HT-2 cells contain sufficient endogenous, stimulus-responsive phospholipase A2 to provide both the cyclooxygenase and lipoxygenase pathways of AA metabolism ith substrate. In contrast, Ca++ ionophores, which are known to stimulate AA release and metabolism in certain cell types, stimulated only AA release but no detectable eicosanoid biosynthesis in HT-2 cells. Experiments with exogenous bacterial phospholipase C suggested that this cell line can also generate free AA for eicosanoid biosynthesis from membrane-derived 1,2-diacylglycerol. These results indicate that multiple intracellular pathways of AA metabolism are present HT-2 cells, and that the stimulus-induced release of AA and the production of eicosanoid second messengers may result from activation of either phospholipase A2 or phospholipase C. PMID- 3088129 TI - Lipoxygenase activity of Pityrosporum in vitro and in vivo. AB - Lipid peroxidation has been investigated both in cultures of Pityrosporum supplemented with different lipid classes and in skin surface lipids from patients affected with pityriasis versicolor. Thin-layer chromatography (TLC) and 2 spectrophotometric methods were used: the indirect thiobarbituric acid test and the direct N,N-diethyl-1,4-phenylene-diammonium sulfate (DEPD) test. The coupling of the DEPD test with the TLC technique performed by different eluent systems allowed the detection of the specific lipoperoxides deriving from the oxidation of the different lipid classes. In the cultures, Pityrosporum was capable of peroxidating not only unsaturated free fatty acids, but also unsaturated triglycerides, cholesterol, and squalene. A similar lipid peroxidation was observed in patients with pityriasis versicolor in skin lipids from areas positive for fungal hyphae and spores and fluorescent under the UV lamp (366 nm). The lipoperoxide values were significantly higher (p less than 0.05) than in skin lipids from normal controls. Hyphae and spore-negative areas of patients with pityriasis versicolor, whether apparently normal or achromic, showed no evidence of a significant lipid peroxidation and neither did skin areas of patients with pityriasis alba. Though further investigations are necessary, it seems reasonable to suggest, in analogy with other biologic systems, that the presence in skin lipids of a significant amount of highly reactive and cytotoxic lipoperoxides may play a role in the pathogenesis of skin alterations in pityriasis versicolor, including damage to melanocytes and resulting achromia. PMID- 3088130 TI - In vitro synthesis of 12-hydroxy-eicosatetraenoic acid is increased in uninvolved psoriatic epidermis. AB - Certain arachidonic acid (AA) metabolites have been detected in psoriatic skin lesions. In this study the capacity of normal epidermis and clinically uninvolved psoriatic epidermis to transform AA into lipoxygenase products was determined in vitro. After incubating homogenized epidermis with exogenous AA, the extracted lipids were isolated by reverse-phase high-performance liquid chromatography. Each chromatographic peak was characterized by its UV absorption spectrum and identified by its coelution with the appropriate authentic standard and by radioimmunoassay of its eluate fraction. Identified compounds were quantitated by integrated UV absorbance. Leukotriene B4 (LTB4) was also identified by neutrophil chemokinesis. Normal epidermis generated 15-hydroxy-eicosatetraenoic acid (15 HETE) and 12-HETE, the latter being more abundant. 5-Lipoxygenase products (LTB4, LTC4, and 5-HETE) were not detected. However, an unknown compound exhibiting a triplet UV absorbtion spectrum with maximum at 274 mm was formed. Its formation was inhibited by 5,8,11,14-eicosatetraynoic acid, but not by indomethacin or a specific 5-lipoxygenase inhibitor (REV 5901). These data suggest that a di-HETE with a triene structure is one possible candidate for the unknown compound. Compared with normal epidermis, the formation of 12-HETE and the unknown di-HETE by uninvolved psoriatic epidermis was increased by 54% and 63%, respectively. The formation of 12-HETE and the unknown di-HETE in uninvolved psoriatic epidermis was stimulated to the same degree in the presence of the phospholipase inhibitor quinacrine. These results indicate that uninvolved psoriatic epidermis has an increased capacity to metabolize free AA into 12-lipoxygenase products. PMID- 3088131 TI - Biochemical characterization of the epithelial basement membrane antigen defined by the monoclonal antibody KF-1. AB - The KF-1 monoclonal antibody has been shown to identify a noncollageneous component of the lamina densa of the basement membrane zone of human skin. In the present work, the monoclonal antibody and the antigen were further characterized. KF-1 monoclonal antibody is an IgG3 immunoglobulin with no binding to staphylococcal protein A. Two squamous carcinoma cell lines--namely, TR131 and TR146--quantitatively express the antigen. Immunofluorescence techniques showed that the antigen is a cell surface antigen, is sensitive to Triton X-100 extraction, and is concentrated in cell areas from which actin fibers are excluded. Immunoblot analysis showed that this monoclonal antibody identifies a 72 kD polypeptide present in TR131 cell extract as well as in cultured human keratinocyte cell extract. PMID- 3088132 TI - Auxotypes, penicillin susceptibility, and serogroups of Neisseria gonorrhoeae from disseminated and uncomplicated infections. AB - We examined auxotypes, penicillin susceptibility, and outer membrane serogroups of 137 strains of Neisseria gonorrhoeae isolated from patients with disseminated gonococcal infection (DGI) and 137 control strains from patients with uncomplicated gonorrhea. We analyzed separately the data for strains isolated from systemic sites in patients with DGI and for strains from local sites in patients with the clinical syndrome of DGI (SDGI) who had negative systemic cultures. We found the nutritional requirement for arginine, hypoxanthine, and uracil (AHU auxotype) significantly more often among DGI strains than among SDGI strains. By using commercially available serogrouping reagents to detect outer membrane protein antigens, we found that regardless of strain auxotype, dissemination correlated best with the presence of protein IA antigens. We did not find that gonococci isolated from DGI are highly susceptible to penicillin. Susceptibility to low concentrations of penicillin correlated only with the AHU requirement, not with serogroup or isolation from a patient with DGI or SDGI. PMID- 3088133 TI - Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections. AB - We studied the mechanism of resistance to imipenem in three clinical isolates of Pseudomonas aeruginosa. Two of these isolates arose from imipenem-susceptible strains isolated during therapy with imipenem and were associated with treatment failure. One of these two strains had previously been broadly resistant to beta lactams; the second acquired resistance to imipenem alone. One isolate of the third strain was resistant to imipenem but susceptible to other antipseudomonal beta-lactams. No isolate contained beta-lactamase activity capable of hydrolyzing imipenem at a detectable rate. Studies of the penicillin-binding proteins of all isolates revealed no differences in the number of proteins, molecular weight of, affinity for penicillin, or affinity for imipenem in any isolate. In each case the resistant isolate lacked one or more outer membrane proteins that were present in a susceptible isolate of the same strain. The observed alterations in outer membrane proteins may be associated with diminished permeability of the bacterial outer membrane to imipenem and may be the major factor responsible for resistance in these isolates. PMID- 3088134 TI - Effects of cyclosporine on pulmonary clearance of Staphylococcus aureus and Pseudomonas aeruginosa. PMID- 3088135 TI - Unique strains of Neisseria gonorrhoeae causing epidemic gonorrhea during the penicillin era: a study of isolates from Denmark. PMID- 3088136 TI - Relation between intestinal parasitosis and appendicitis. PMID- 3088137 TI - Histopathological changes in experimental schistosomiasis mansoni before and after praziquantel therapy. PMID- 3088138 TI - Ultrastructure of cyst wall of sarcocystis of Mus musculus, and reaction to cyst wall. PMID- 3088139 TI - A clinico-parasitological and immunological studies on concomitant mansoniasis and filariasis in Egypt. PMID- 3088140 TI - Electrophoretic study of alkaline phosphatase isozymes of Schistosoma mansoni worm and hamster. PMID- 3088142 TI - The efficacy of praziquantel in Egyptian schistosomiasis. PMID- 3088141 TI - Haemogregarina arabica sp. nov. (Eucoccidiida:Sporozoea) parasitizing Rana ridibunda and Bufo dhufarensis in Saudi Arabia. PMID- 3088143 TI - Enzyme linked immunosorbent assay for the evaluation of praziquantel therapy in different groups of bilharzial patients. PMID- 3088144 TI - Blood picture and liver function tests before and after praziquantel therapy of Egyptian bilharzial patients. PMID- 3088145 TI - Role of IgE in schistosomiasis. PMID- 3088146 TI - Further observations on the ultrastructure of the schistosomal pigment in human liver. PMID- 3088148 TI - Vertical transection of the alar cartilages in unilateral cleft noses. AB - Nasal deformities in unilateral cleft patients require more-or-less modifications of the nasal tip. The techniques of Goldman and Ponti that have been recommended initially for esthetic rhinoplasties in non-cleft noses include the vertical transection of the alar cartilage on both sides. The first technique is performed in noses that require an extensive modification, especially in large noses with thick seborrheic skin, with a short columella or a distinct asymmetry. The second technique is utilized for slight deformities with thin skin, nearly symmetric and a sufficient columella length. Both techniques have proven to obtain good results, also in cleft nose surgery. The operative steps of the techniques are described and some case reports are presented. Finally, a gradual schedule for the cleft nose repair is discussed and the advantages of the techniques described are pointed out. PMID- 3088147 TI - Regulation of human gamma-interferon and beta-interferon gene expression in PHA activated lymphocytes. AB - Two interferon (IFN) messengers were synthesized in phytohemagglutinin (PHA) activated lymphocytes: IFN-gamma mRNA and a messenger hybridizing with the IFN beta 2 probe. They were induced rapidly and declined at a stage when overall RNA was still efficiently transcribed. The IFN-beta 2 mRNA (15S) present in the lymphocytes was slightly different from its fibroblastic counterpart (14S). The kinetics of the accumulation and decay of both lymphocyte IFN messengers differed when assessed by hybridization with the two IFN probes, IFN-gamma mRNA was not detected before mitogenic activation and accumulated for up to 15 h postactivation, while IFN-beta 2 mRNA accumulated even in the absence of PHA activation for up to 5 h, even though the activation raised the IFN-beta 2 mRNA level at 5 h. The disappearance of IFN messengers was prevented when cycloheximide was added 5 h after PHA activation, when the transcription of both messengers had already been turned on, suggesting the presence of the repressor mechanism proposed for IFN-beta 1 and IFN-beta 2 mRNAs in fibroblasts. In the absence of PHA activation, cycloheximide did not induce IFN-beta 2 mRNA transcription as it did in fibroblasts and moreover prevented the accumulation of the messenger observed in the control cells. In contrast to IFN-beta 2 mRNA, cycloheximide treatment of lymphocytes produced a slight accumulation of IFN gamma mRNA. This accumulation was already detectable 6 h posttreatment and its level remained unchanged for up to 24 h. Addition of actinomycin D, 5 h after PHA activation, did not impair the shut off and accelerated the decay of IFN messengers. PMID- 3088149 TI - Skeletal remodelling in the temporomandibular joint after oblique sliding osteotomy of the mandibular rami. AB - Skeletal remodelling of the temporomandibular joints took place in 80% of cases after oblique sliding osteotomies of the rami. The new bone formation was found in both the condylar and temporal parts of the joint. It was mostly located on the posterior surface of the condyle and in the roof of the temporal part of the joint. No differences in skeletal remodelling were found between wiring and nonwiring cases. PMID- 3088150 TI - The reaction of the periodontium to different types of splints. (I). Clinical aspects. AB - To study the influence of splints on the periodontia over a period of time, Obwegeser and Merkx splints were applied on beagles. Clinical evaluation using different periodontal parameters was carried out before, and 48 h, 3 weeks and 6 weeks after splinting. It was shown that both splints act as plaque-retentive devices and provoke gingival inflammation. A statistically significant difference between both splints could, however, only be demonstrated for the plaque index. PMID- 3088151 TI - The reaction of the periodontium to different types of splints. (II). Histological aspects. AB - To study the influence of splints on periodontal tissues, Obwegeser and Merkx splints were applied to beagles. Histological evaluation was performed after splinting periods of 48 h and 6 weeks. After 48 h, gingivitis had developed when using both types of splints. After 6 weeks, the adverse effects of the splints were more predominant. Gingivitis had become severe and mild periodonitis had developed. In the case of Merkx splints, the periodontal ligament appeared to be somewhat less affected but the condition of the gingiva appeared to be somewhat worse than in the case with Obwegeser splints. For both types of splints, it is important that clinical application should be attended by measures not only to reduce plaque accumulation, but also to minimize trauma due to their application and continuous mechanical irritation of the tissues. PMID- 3088152 TI - Photoelastic stress analysis on mandibular osteosynthesis. AB - An experimental study concerning mechanical behaviour and stability through mandibular osteosynthesis has been carried out. 3 different kinds of mandibular osteosynthesis: figure-of-8 wiring; ASIF--Swiss Association for the Study of Internal Fixation - compression plate; monocortical juxta-alveolar miniature screwed plate (Champy plate), were analysed in photoelastic model experiments. The strain distribution differs remarkably according to these 3 methods as well as stability against loading forces. PMID- 3088153 TI - Titanium mesh and particulate cancellous bone and marrow grafts to augment the maxillary alveolar ridge. AB - A detailed explanation of a surgical technique for grafting of deficient maxillary alveolar ridges is presented. In addition, a technical modification, for use where a fibrous hypermobile soft tissue ridge exists over the deficient maxilla is outlined. Results to date have been excellent as has been the follow up (12-48 months); continued used of this technique and its modification is encouraged. PMID- 3088154 TI - Comparison of complications after bone removal from lateral and medial plates of the anterior ilium for mandibular augmentation. AB - 6 patients whose mandibles were to be augmented with autogenous bone were divided into 2 groups of 3 patients each. In one group, autogenous donor bone was harvested from the medial plate of the anterior ilium, whereas in the second group bone was harvested from the lateral plate. Although some clinicians have asserted that there is less morbidity when bone is harvested from the medial plate, no difference between the 2 groups was noted in the length of hospitalization, amount of blood loss during surgery, incidence of seroma development, or need for a cane or walker. The decision to remove bone from the lateral or medial plates should be based on surgical access rather than incidence of complications. PMID- 3088155 TI - Indications for surgical removal of supernumerary teeth in the premaxilla. AB - Usually supernumerary teeth in the maxilla are removed surgically, often due to retention of the permanent teeth in the region, but in certain cases the supernumerary teeth do not cause alterations in the eruption, position or integrity of the permanent dentition. This study was performed in order to review the indications for such surgical removal. The patient records of 208 patients with supernumerary teeth during the period of 1970-81 were reviewed retrospectively. Of these patients, 52 non-operated were furthermore examined clinically and radiographically in 1982; mean observation time 7.3 years (1-22 years). Results showed that none of the 52 non-operated patients had any symptoms or pathologic conditions related to the supernumerary teeth. In 37%, progressive resorption of the supernumerary teeth was seen, and in 24% the pericoronary space was markedly reduced compared to the first examination. The position and morphology was found to have influence on the prevalence of retention of the permanent incisors (p less than 0.0001). Widening of the pericoronary space during the observation period of the non-operated patients was not seen in any of the cases. Of the total of 262 teeth, 2 well-defined pericoronary cyst (pericoronary space greater than or equal to 5 mm) were found. From the present study, it is concluded that supernumerary teeth in the premaxilla may cause pathological conditions. However, each case must be considered individually concerning surgical treatment, and if no retention of permanent teeth or pathological conditions are present, observation with regularly radiographic controls is advisable. Enlarged pericoronary space (1-3 mm) does not alone seem to indicate surgical treatment. PMID- 3088156 TI - Autotransplantation of maxillary canine teeth. A follow-up of 35 cases up to 4 years. AB - 35 cases of autotransplantation of nonendodontically treated maxillary canines were followed for up to 4 years and were assessed according to loss of the transplanted tooth, onset of sensibility, mobility, intact lamina dura and presence of tooth resorption. The results of this study compare favourably with other studies and favour the hypothesis that little is to be gained by not endodontically treating autotransplanted teeth immediately after splint removal. It is also suggested that immobilization by means of a rigid splint, removing the tooth from occlusal forces, may account for the relatively low incidence of resorption in this series. PMID- 3088157 TI - Anaerobic bacteria in dentoalveolar abscesses. AB - The present study was initiated to determine the bacteriology of 40 orofacial abscesses of dental origin in patients who had taken antibiotics for several days. Bacteria were isolated from all but 2 specimens. Aerobic or facultative anaerobic bacteria were isolated in 21 cases, obligate anaerobic bacteria in 17 cases, whereas in 11 cases, polymicrobial growth was revealed. The average number of bacterial species was 2.1 per specimen. Gram positive aerobic micro-organisms predominated, namely, Staphylococcus epidermidis followed by Streptococci (group A) and Staphylococcus aureus. Among obligate anaerobes, Gram positive micro organisms, peptostreptococci and peptococci were more often isolated, in the following decreasing order: Ps. productus, Ps. intermedius, Ps. parvulus, Ps. anaerobius, Pc. constellatus, Pc. prevotii. Gram negative anaerobic rods were detected in a small number of cases, namely B. corrodens, B. fragilis, B. melaninogenicus, B. ochraceus, B. oralis. Quantitative determination did not show any meaningful difference between aerobic and anaerobic isolates. Susceptibility tests against a series of antibiotics showed that ampicillin was the most active in aerobes and cefoxitin in anaerobes. PMID- 3088158 TI - Idiopathic submandibular abscesses in children. AB - Idiopathic submandibular abscesses are often observed in young children and the report concerns 31 children treated over a period of 3 years. Their origin is unknown. As all these abscesses were lymph node abscesses in the submandibular region, it is assumed that they are due to minor oral and nasal cavity traumatic lesions secondarily infected. Antibiotic treatment and surgical drainage resulted in quick resolution and recurrences were never observed. PMID- 3088159 TI - Immunohistochemical demonstration of carcinoembryonic antigen (CEA) on tissue sections from squamous cell head and neck cancer and plasma CEA levels of the patients. AB - 45 squamous cell head and neck cancers including 36 with carcinoma of the oral cavity and 9 with carcinoma of the maxillary sinus were examined immunohistochemically for the presence of CEA. 12 of 30 carcinomas of the oral cavity and 7 of the 9 carcinomas of the maxillary sinus had tumors containing CEA. This difference in the occurrence of CEA was statistically significant. The mean plasma CEA level of 36 patients with carcinoma of the oral cavity and 7 patients with carcinoma of the maxillary sinus was 1.95 +/- 1.72 ng/ml and 3.70 +/- 3.53 ng/ml, respectively. Significant elevation of plasma CEA levels was found only in the stage-IV group patients with carcinoma of the oral cavity as compared with the stage-I group patients. In the 3 patients having plasma CEA values exceeding 5 ng/ml at the time of pretherapy, plasma CEA levels were decreased to below 2.5 ng/ml with the cancer treatment followed by the complete remission. These findings indicate that plasma CEA as a tumor marker in squamous cell head and neck cancer is meaningful in a small proportion of the cancer patient population. PMID- 3088160 TI - Posterior capsulitis of the temporomandibular joint. AB - Posterior capsulitis, which is characterized by pain and inflammation localized above and behind the condyle of the mandible, usually develops as a result of premature contacts in dental occlusion. The pain at the affected side is related to the severe spasm of M. Pterygoideus Lateralis or the splinting action of the masticatory muscles. This condition can be readily treated by occlusal grinding of these premature contacts after a definite diagnosis. The amount of grinding on the teeth varies according to the localization of premature contacts and the pain at the joint. This study covers 123 patients diagnosed as having posterior capsulitis and the results are presented. PMID- 3088161 TI - Exfoliative cheilitis--a factitious disorder? AB - Exfoliative cheilitis is an uncommon lip lesion usually of great concern to the patient and quite refractory to treatment. The available literature was surveyed, and 3 cases have been described to illustrate various aspects of the condition. The difficulty of treating such lesions has been discussed, and a proposition put forward that the lesions are of a factitious nature. PMID- 3088163 TI - Candida albicans in median rhomboid glossitis. A postmortem study. AB - To investigate the possible role of Candida in median rhomboid glossitis, the presence of Candida was looked for both in the foramen cecum area and the lateral borders of 100 human cadaver tongues. Almost equal %s were found in both locations. Although extrapolation of findings from postmortem material to normal subjects is somewhat hazardous, the results seem to question the importance of Candida in the etiology of median rhomboid glossitis. PMID- 3088162 TI - Sialochemistry in mucosal lesions of the tongue: electrolytes and total protein. AB - A total of 39 patients with tongue diseases and 17 controls were subjected to chemical analysis of saliva to determine whether tongue lesions are correlated with the composition of the saliva. The salivary flow rate, total protein, phosphate and electrolyte content (Na, K, Ca) were measured in unstimulated and stimulated saliva. The results indicate that disturbed salivary secretion could be revealed in patients with filiform atrophy and those with hairy tongue. The hormonal imbalance might be a factor in the etiology of filiform atrophy and geographic tongue. No significant difference between the sialochemistry of patients with fissured tongue and controls was found. PMID- 3088164 TI - False (traumatic) aneurysm of the facial artery caused by a foreign body. AB - False (traumatic) aneurysms of the facial regions are relatively rare. The facial artery is most often involved. A case of false aneurysm caused by penetration of the facial artery by a small, sharp object is reported. The object was lodged in the wall of the aneurysm. Metallurgical investigation identified the foreign body as a fragment of a metal hammer. This finding may be important from a forensic point of view. PMID- 3088166 TI - Erythema multiforme and Mycoplasma pneumoniae infection. Report and discussion of a case presenting with stomatitis. AB - A case report is presented in which a respiratory tract infection with M. pneumoniae appears to have provoked a generalised mucocutaneous disease, described as Stevens Johnson syndrome. The patient possessed complement-fixing antibodies to M. pneumoniae to a titre of 1/2048 compared with the general population titre of 1/32. The oral mucosal lesions are described in particular and a likely pathogenesis of erythema multiforme is discussed. PMID- 3088165 TI - Stomal sepsis and fatal haemorrhage following tracheostomy. AB - A case of stomal sepsis and fatal haemorrhage following an emergency tracheostomy in a 28-year-old woman is presented. It is proposed that major haemorrhage can occur in the absence of a large vessel lesion as a result of local sepsis and inflammation. Infection in this setting can be predicted to be polymicrobial in origin and attention is therefore drawn to the need for early prophylactic antimicrobial therapy as well as the need for meticulous care of the stomal site. PMID- 3088167 TI - Oral cysticercosis. AB - A 35-year-old Indian male with nodules in the tongue, lower lip and subcutaneous tissues and convulsions of recent onset is presented. Surgical excision of the nodules confirmed the clinical diagnosis of cysticercosis and relieved the lingual discomfort. This is the 26th case of oral cysticercosis being reported. PMID- 3088168 TI - Chronic osteomyelitis of the jaws. AB - The incidence of osteomyelitis has been greatly reduced since the advent of antibiotics. In many 3rd World countries, however, numerous cases of severe advanced osteomyelitis still present annually. A case of subacute osteomyelitis is reported and the pathology and clinical features of chronic osteomyelitis are reviewed. PMID- 3088169 TI - Maxillary angiosarcoma. AB - A malignant tumor of mesenchymal origin, angiosarcoma, is a rare entity deriving from the endothelium of the blood vessels, that very infrequently is encountered in the jaws. 46 such cases have only been reported. PMID- 3088170 TI - Papillary cystic adenocarcinoma of minor salivary glands. PMID- 3088171 TI - [An outbreak of well water-associated food-poisoning caused by enterotoxigenic Escherichia coli O159:H20]. PMID- 3088173 TI - [Characterization of beta-lactamases in Legionella pneumophila]. PMID- 3088172 TI - [Significance of fecal Bacteroides in hepatic encephalopathy with hyperammonemia]. PMID- 3088174 TI - [The long term chemotherapy with erythromycin in chronic lower respiratory tract infections--first report: comparison with amoxicillin]. PMID- 3088176 TI - [Influenza vaccination in patients with chronic renal failure]. PMID- 3088175 TI - [The long term chemotherapy with erythromycin in chronic lower respiratory tract infections--second report: including cases with Pseudomonas infections]. PMID- 3088177 TI - [Echovirus type 16 infection (Boston exanthem)--clinical review of 103 cases in Kasahara]. PMID- 3088178 TI - [Recent observation on sepsis in infancy and childhood (1980-1984). Part 1. The survey through questionnaires in forty-eight pediatric institutions in Japan, with reference to the incidence of sepsis by year and by age as well as causal organisms]. PMID- 3088179 TI - [A case of transient Listeria monocytogenes bacteremia recovering without antimicrobial chemotherapy]. PMID- 3088181 TI - [60th congress of the Japanese Association for Infectious Diseases. Tokyo, April 24-26, 1986. Abstracts]. PMID- 3088180 TI - [Case of fulminant pneumonia caused by Legionella bozemanii]. PMID- 3088182 TI - Modification of the thermal sensitivity of the murine foot and tumour by prior hypoxic treatment. AB - The response of Furth's murine mastocytoma to heat and the effect of prior heating and hypoxic treatment by clamping on the thermal sensitivity of the murine foot and the tumour were investigated. Two different-sized tumours, with average diameters of 3-4 mm and 7-8 mm were used. The tumour response to heat was evaluated by tumour growth (TG) time. Thermotolerance developed in both the foot and tumour tissues by a prior heating for 5 or 10 min at 45 degrees C. Hypoxic treatment resulted in dual effects on tumours. A 10 or 20 min hypoxic pretreatment increased thermal sensitivity of the tumour, while more than a 30 min hypoxic pretreatment induced thermotolerance. In contrast, a 20 min hypoxic treatment induced thermotolerance in the normal tissues. These results indicate that an appropriate period of prior hypoxic treatment may lead to a differential response between normal and tumour tissues. PMID- 3088183 TI - [Studies on inhibin in human follicular fluid]. AB - In order to investigate whether inhibin (FSH-suppressing activity) is present in human follicular fluid (hFF) and whether inhibin in hFF could be correlated with the FSH level in peripheral serum, the effect of hFF on FSH secretion was studied using monolayer culture of rat anterior pituitary cells. Dextran-coated charcoal (DCC)-treated hFF exerted an inhibitory effect on pituitary FSH secretion but not on LH. The inhibitory effect of hFF upon basal FSH secretion was different from those of steroids such as estradiol, progesterone, testosterone and androstenedione. hFF inhibited the LHRH-stimulated secretion of both FSH and LH. Since hFF and porcine follicular fluid (pFF) produced a parallel dose-dependent decrease of basal FSH secretion, the same suppressing activity may be present in both hFF and pFF. Inhibin activity increased gradually during the follicular phase, but decreased in the luteal phase. Inhibin activity in hFF except during preovulatory surge showed a significant inverse correlation with the FSH level in peripheral serum. These results might indicate that inhibin activity in hFF increased according to follicular maturation and that inhibin (non-steroidal substance) may be one of the important regulators of FSH secretion in the human pituitary. PMID- 3088184 TI - In vitro studies on dermal granulomas of human leprosy: characterization of cells using monoclonal antibodies. AB - Single cell suspensions from granulomas of leprosy cases were prepared to enable an in vitro study on the characteristics of infiltrating cells. In all, biopsies from 21 untreated cases of tuberculoid leprosy and lepromatous leprosy were analyzed. The granulomas were found to contain lymphocytes and macrophages. The numbers of lymphocytes were higher in the suspensions of tuberculoid granulomas in comparison to lepromatous granulomas. A high percentage of lymphocytes from tuberculoid granulomas expressed OKT11 and Ia-like antigens, thereby indicating the presence of activated T cells. The proportion of Leu3a+ cells was greater in comparison to OKT8+ cells in these granulomas. In lepromatous granulomas, only a few positive lymphocytes expressing OKT11 or OKT8 antigens were observed. The ratio of Leu3a+:OKT8+ cells (2.79 +/- 0.61) was higher in the tuberculoid granulomas than in the lepromatous granulomas. Most macrophages from both types of granulomas expressed Ia-like antigens. PMID- 3088185 TI - [An epidemiological study on the ossification of the anterior longitudinal ligament of the spine]. AB - An epidemiological study was carried out in connection with the multiphasic screening examination of 1,057 people (442 men and 615 women) in the village of Yachiho. The purpose of this study was to define the etiology of OALL (ossification of the anterior longitudinal ligament) and disc narrowing. The prevalence of disc narrowing increased with age, but OALL was not correlated with aging. OALL was found more frequently in men, but disc narrowing showed no difference between each sexes. The body height and weight-height index were higher in the OALL cases. The body height shrinkage by aging was greater in the patients with disc narrowing cases. The index of thoracic kyphosis was higher in the OALL cases than in the patients with disc narrowing ones. OALL was associated with ossification of the other ligaments of the spine, but disc narrowing was not. This study suggests that despite some similarities, OALL is etiologically different from disc narrowing. PMID- 3088186 TI - [An immunochemical study of extracts from synovial fluid cells in rheumatoid arthritis]. AB - Extracts were obtained by ultrasonic vibration from synovial fluid cells of patients with rheumatoid arthritis and rabbit antisera against the extracts were prepared. The antisera were absorbed with normal human plasma. Double immunodiffusion revealed two precipitin lines between the extracts and the antisera. These antigens were called P1 and P2. P1 and P2 antigens were detected in 17 (94%) and 10 (56%), respectively, out of 18 rheumatoid synovial fluids. In osteoarthritic fluids, P1 antigen was detected in only one (4%) of 25 cases but P2 antigen was never detected. The P1 antigen was not inactivated by trypsin or deoxyribonuclease but P2 antigen was digested by trypsin suggesting its protein character. Though it is not clear that these antigens are specific for rheumatoid arthritis, these antigens in synovial fluid cells seem to be associated with the rheumatoid synovial fluid. PMID- 3088188 TI - Cost-benefit of laboratory computer systems. AB - The benefits and costs of a computer laboratory information system have been evaluated in three military hospitals, using a pre- and postimplementation comparison of time spent by laboratory and medical staff on information-handling activities, turnaround time for laboratory results, and staff perceptions of performance. The evaluation indicates that the laboratory information system is very cost-effective. A major benefit is the reduction in nursing staff time required to obtain laboratory test status and results. PMID- 3088187 TI - [Histopathological studies of the osteophytes and ossification of the posterior longitudinal ligament (OPLL) in the cervical spine]. AB - To obtain information on ossification around the vertebral body of the cervical spine, we carried out histopathological investigation on 30 autopsy cases. The results were as follows; Intervertebral discs were untouched, anterior osteophytes developed along the anterior longitudinal ligament and they corresponded to anterior spur in spondylosis deformans. Posterior osteophytes around the posterior edges of vertebral body resulted in intervertebral insufficiency, and corresponded to hypertrophic spur in osteochondrosis. Histopathological findings of hyperostotic anterior osteophytes were similar to anterior osteophytes, but in the former there were advanced osteophyte formations. In OPLL of the segmental type, intervertebral discs were degenerated, and ossified mass did not involve the posterior longitudinal ligament of the parts of discs. With regard to morphological appearance and the tendency of increasing ossification, OPLL of the continuous type was similar to hyperostotic anterior osteophytes, without involvement of intervertebral disc. OPLL of the distinctly continuous type was differentiated from that of the segmental type. PMID- 3088189 TI - Maximizing the benefits of health care information systems. AB - Information systems can improve cost control, increase the timeliness and accuracy of patient care and administration information, increase service capacity, reduce personnel costs and inventory levels, and improve the quality of patient care. However, experience shows that most of these benefits will not occur automatically following system implementation. Operational problems may exist that diminish information timeliness, accessibility, and accuracy; policies and procedures may not have been sufficiently tailored to reflect the realities and intents of the systems; and personnel tasks may not have been adequately restructured. In order to realize the full potential of information systems, health care organizations must plan for and implement strategies that are designed to maximize such benefits. This paper describes a method for developing benefits maximization strategies. The processes used to define strategies and their outcomes are presented. PMID- 3088190 TI - The Computerized Severity Index. A new tool for case-mix management. AB - We describe the new Computerized Severity Index (CSI) that is obtained from an expanded discharge abstract data set, based on a 6th-digit severity addition to the ICD-9-CM coding system. The new 6-digit code book (called ICD-9-CMSA) is used to label existence and severity of each principal and secondary diagnosis. It can be used to produce an overall severity of illness level for each hospital inpatient. The impact of severity-adjusted DRGs on prospective payment and uses of the CSI for assessing quality of care, efficiency, physician practice profiles, and prediction of posthospital resource needs are discussed. PMID- 3088191 TI - The heart in protein-energy malnutrition (PEM). PMID- 3088192 TI - Psychomotor performances and subjective feeling studies with antihistamine. PMID- 3088193 TI - Aerobic and anaerobic correlates of mechanical work by gastrocnemius muscles of the aquatic amphibian Xenopus laevis. AB - Isolated, saline-perfused gastrocnemius muscles of Xenopus laevis were used to assess the relationships between aerobic and anaerobic metabolism during conditions of rest, isotonic contraction and recovery. The major part (85%) of the energy used during 25 min of isotonic contractions in the saline-perfused muscles was from anaerobic rather than aerobic sources. However, the small contribution made by oxidative metabolism during activity can be attributed, in part at least, to limitations imposed by the rate of perfusion and the low O2 capacity of the perfusate. The respiratory exchange ratio (R = VCO2/VO2) of saline-perfused gastrocnemius muscles of Xenopus was 0.82 at rest, increasing to values well above 1.0 during activity. The elevated R value is consistent with liberation of CO2 by metabolic acid titration of the bicarbonate buffer system of the saline perfusate. Recovery from exercise was characterized as a period of net CO2 retention (R values of 0.4) presumably reflecting a replenishment of depleted CO2 stores. Depending on the acid-base status of the venous outflow from the isotonically contracting muscles, hydrogen ions were found to be released at either a greater rate (alkalosis) or slower rate (acidosis) than that of lactate. PMID- 3088194 TI - Mechanisms of pH regulation in lamprey (Lampetra fluviatilis) red blood cells. AB - Mechanisms regulating the red cell pH in lamprey (Lampetra fluviatilis) were studied using the ammonium chloride prepulse technique. The cells were initially incubated in a physiological saline containing 20 mmol l-1 ammonium chloride, and intracellular pH measured with the DMO technique. Ammonium chloride was then rapidly removed by centrifugation, and the changes in the intracellular pH followed. The intraerythrocytic pH is primarily regulated by an amiloride sensitive sodium/proton exchange. When sodium is present in the incubation medium, the intracellular pH rapidly recovers from the acidification associated with the removal of ammonium chloride from the incubation. When sodium is removed from the incubation medium, intracellular pH does not recover, and when the cells are treated with 10(-3) mol l-1 amiloride in the presence of sodium, carbon dioxide and bicarbonate, the intracellular pH recovery is drastically reduced. The movements of carbon dioxide, its consecutive catalysed hydration and dissociation to protons and bicarbonate and, possibly, movements of bicarbonate out of the cell acidify the cell contents. This is shown by the observation that the steady-state intracellular pH is higher in a HEPES-buffered medium than in a CO2/HCO3(-)-buffered medium at the same extracellular pH. The acidification is dependent on cellular carbonic anhydrase activity, present in lamprey red cells, which speeds up the hydration reaction. When the action of carbonic anhydrase is inhibited by acetazolamide, removal of ammonium chloride from the incubation medium does not cause intracellular acidification. PMID- 3088195 TI - Gamma interferon and lymphotoxin, released by activated T cells, synergize to inhibit granulocyte/monocyte colony formation. AB - We have shown that lymphocytes stimulated by PHA produce colony-forming unit of granulocyte/monocyte (CFU-GM)-stimulating and -inhibiting activities, IFN-gamma, and lymphotoxin (LT). IFN-gamma is necessary for inhibition of CFU-GM by PHA conditioned medium (CM), as shown by experiments in which removal of IFN-gamma from PHA-CM abrogated inhibition. However, experiments in which rIFN-gamma was added to IFN-gamma-depleted PHA-CM revealed the presence, in PHA-CM, of other factors that act in synergy with IFN-gamma to inhibit CFU-GM. Fractionation of PHA-CM on a Sephadex G-100 column was used to separate IFN-gamma and LT. Colony inhibiting activity was eluted in fractions that contained both IFN-gamma and LT activities, identifying LT as a factor present in PHA-CM that synergizes with IFN gamma to inhibit CFU-GM. Treatment of PHA-CM with mAb against either IFN-gamma or LT completely abrogated the colony-inhibiting activity, demonstrating a requirement for both lymphokines in PHA-CM-induced inhibition of CFU-GM. Experiments using rIFN-gamma and preparations of purified LT confirmed that neither lymphokine alone, when added to bone marrow cells at the concentrations present in PHA-CM, strongly inhibited day 7 or day 14 CFU-GM, but that the two lymphokines, added together, behaved synergistically to inhibit CFU-GM by up to 70%. The inhibition observed using purified preparations of lymphokines shows that synergy between IFN-gamma and LT is sufficient to explain PHA-CM-induced inhibition of CFU-GM. Our findings suggest that activated T cells regulate hematopoiesis through the release of inhibitory as well as stimulatory factors, and that the simultaneous production of IFN-gamma and LT may represent a mechanism of suppression of hematopoiesis in the cases of bone marrow failure associated with the presence of activated T cells. PMID- 3088197 TI - Antiimmunoglobulin-treated B cells respond to a B cell differentiation factor for IgG1. AB - We have determined whether B cells previously activated by anti-Ig (anti-Ig blasts) are responsive to lymphokines that induce isotype switching. Culture of anti-Ig blasts with a mixture of lymphokines, including BSF-1, resulted in marked secretion of IgM and IgG1, but not other IgG isotypes. The IgG1 response of anti Ig blasts to lymphokines was 13-fold greater than was observed with splenic B cells. B cell blasts induced by 8-mercaptoguanosine or dextran sulfate did not secrete high levels of any IgG isotype in response to lymphokines alone. An mAb against BSF-1 suppressed the IgG1 response of anti-Ig blasts, but not the IgM response to lymphokines. These data suggest that anti-Ig-treated B cells respond to at least one of the effects of BSF-1. PMID- 3088196 TI - Primary structure of IgE monoclonal antibodies expressing an intrastrain crossreactive idiotype. AB - We have obtained amino acid sequences (by mRNA and amino acid sequencing) for two IgE kappa mAb that have specificity for the Ars hapten group and are related to the major idiotypic family, CRIA (crossreactive idiotype A), in the A strain of mouse. One mAb, SE20.2, fully expresses CRIA; the other, SE1.3, possesses some but not all of the characteristic idiotopes. Both IgE proteins contain VH and V kappa segments that are closely related to those associated with CRIA. The D segment of SE20.2 is also typical of CRIA+ mAb, but that of SE1.3 is one amino acid residue longer. Chain recombination experiments indicated that the L chain of SE1.3 is fully capable of supporting CRIA expression. Its deficiency with respect to idiotopes of CRIA was attributed to the extra amino acid in the D region and/or substitutions in the VH segment. A major objective was to ascertain the frequency of somatic mutations in IgE. For the VH segment (amino acids 1-98) of SE20.2, there are only three nucleotide differences and one uncertainty with respect to the nucleotide sequence of the germline gene associated with CRIA. A somewhat higher frequency of substitutions is present in the VH segment of SE1.3. The VK amino acid sequences of the IgE proteins are nearly identical to those of a prototype of the CRIA family, mAb R16.7. The results are discussed with reference to the mechanism of the IgM to IgE switch. PMID- 3088198 TI - Administration of group A streptococcal cell walls to rats induces an interleukin 2 deficiency. AB - Intraperitoneal administration of group A streptococcal cell walls to Lewis rats induces a chronic arthritis, whereas the Fischer strain is resistant to the development of the lesion. Spleen cells from cell wall-treated rats (Lewis and Fischer) are deficient in the synthesis of IL-2. Using an mAb directed against the rat IL-2-R, the present studies indicate that the expression of IL-2-R on spleens of cell wall-treated rats is normal. However, the addition of exogenous IL-2 to spleen cells cultured with Con A does not stimulate the mitogenic response. PMID- 3088199 TI - A subset of natural killer cells in peripheral blood displays a mature T cell phenotype. AB - Normal human PBMC were analyzed for the presence of cells expressing both T3 and NKH1 antigens, using direct two-color immunofluorescence. In six individuals, NKH1+T3+ cells were found to represent 2.5% of PBMC and 24% of the total number of NKH1+ cells. Purified NKH1+T3+ cells were shown to have the typical morphology of large granular lymphocytes (LGL). NKH1+T3+ cells also exhibited spontaneous cytotoxicity against K562 target cells and this lytic activity could be inhibited by anti-T3 mAb. Similar results were obtained with NKH1+T3+ cells cultured in vitro in lymphocyte-conditioned medium. Taken together, these results indicate that NKH1+T3+ cells represent a unique population of NK-active cells in normal peripheral blood. Although these cells exhibit LGL morphology and NK activity, this appears to be mediated through a functional T cell-like receptor for target antigen. PMID- 3088200 TI - Lack of expression of the VHS107 gene family in the lipopolysaccharide-sensitive B cell subset of X-linked immunodeficiency-defective mice. AB - The expression of the VH T15 gene product was analyzed in the sera and in the supernatants of polyclonally activated B cells of X-linked immunodeficient (xid) mice. We found that defective males, contrary to normal females, do not express the VH T15 gene product even on antibodies devoid of anti-PC specificity. RNA analysis of polyclonally activated cells with VH specific probes revealed that xid-defective B cells do not express the entire S107 or part of the J606 VH family. Members of the J558 family, on the other hand, are equally well expressed among defective males and normal female B cells. These results strongly suggest that VH families are asymmetrically represented among B cell subsets. PMID- 3088201 TI - Listeria monocytogenes-reactive T lymphocyte clones with cytolytic activity against infected target cells. AB - Lyt-2+ T cell clones were established from Listeria monocytogenes-infected mice. The clones secreted IFN-gamma after stimulation with spleen cells from L. monocytogenes-infected mice plus IL-2. Spleen cells from normal mice were not stimulatory. Furthermore, cloned T cells lysed L. monocytogenes-infected macrophages. Cytolysis was antigen-specific and H-2K-restricted. These findings suggest a role for specific cytotoxic T cells in the immune response to intracellular bacteria. PMID- 3088202 TI - aIr-1, a newly found locus on mouse chromosome 16 encoding a trans-acting activator factor for MHC class II gene expression. AB - RJ 2.2.5 is a human B cell line that has lost the capacity to express MHC class II genes. The human class II-positive phenotype is restored in somatic cell hybrids between RJ 2.2.5 and mouse spleen cells. By karyotype and molecular studies of an informative family of hybrids we have now shown that the reexpression of human class II gene products, as well as the maintenance of the mouse class II-positive phenotype, correlates with the presence of mouse chromosome 16. Thus, the existence on this mouse chromosome of a newly found locus, designated by us aIr-1, that determines a trans-acting activator function for class II gene expression, is established. Possible implications of this finding are discussed. PMID- 3088204 TI - Terminal maturation of resting B cells by proliferation-independent B cells differentiation factors. AB - Using response to four different BCDF preparations as a model of B cell maturation, we have shown that induction of B cell proliferation abrogates terminal maturation of these cells. In fact, response to some BCDFs can occur in the presence of inhibitors of DNA replication, suggesting that there are proliferation-independent as well as proliferation-dependent BCDFs. These findings cannot be explained by changes in the kinetics of the BCDF response, nor can they be reversed by repletion of media or changing cell densities. Proliferation-independent BCDFs appear to exert their effects on dense, resting 4F2- B cells rather than more activated B cells. This is in contrast to B cell differentiation signals of IL-2 alone or SAC and IL-2 in concert. These data suggest that the current models of B cell activation and maturation may require some reorganization, relegating the proliferative phase of B cell maturation to a lesser role. In addition, evidence is provided for the fact that the resting B cell may have the full complement of receptors for BCDF as well as BCGF and BCPF and may help account for the inherent nonspecificity of the immune response. PMID- 3088203 TI - Sequences and repertoire of human T cell receptor alpha chain variable region genes in mature T lymphocytes. AB - 24 human T cell receptor alpha chain messages have been examined by cDNA sequence analysis and Southern blot. The data indicate that there are approximately 40 alpha chain T cell receptor variable gene segments, which can be divided into 12 families. Comparison of the J gene segments from the cDNAs to previously determined germline J alpha sequences places the number of J alpha gene segments over 21, and indicates their number to be approximately 55. Identical nucleotide sequences in independent isolates of V alpha and J alpha gene segments indicate that hypermutation may not be a common mechanism for the expansion of diversity in these genes, and suggest that the major source of diversity within the alpha chain repertoire is a result of recombinational joinings between germline V alpha and J alpha sequences, combined with imprecise junctional joining. Analysis of the V regions of these alpha chain messages reveals the presence of three domains of hypervariability roughly analogous to the CDR1, CDR2, and CDR3 regions of immunoglobulin. PMID- 3088206 TI - Murine hematopoietic cells with pre-B or pre-B/myeloid characteristics are generated by in vitro transformation with retroviruses containing fes, ras, abl, and src oncogenes. AB - In vitro infection of bone marrow or fetal liver cells with retroviruses containing fes, abl, ras, or src oncogenes resulted in the transformation of early B lineage cells. All cell lines tested possessed rearrangements at the Ig heavy chain locus and some had rearrangements at the K chain locus. The majority of the lines corresponded phenotypically to Lyb-2+, Ly-5(B220)+, ThB- large pre-B cells, although some were classified as pro-B cells because of their Lyb-2+, Ly 17+, Ly-5(B220)- phenotype. We identified two cell lines that contained subpopulations of cells that coexpressed the B lineage antigens Lyb-2 and Ly 5(B220) and the myeloid lineage antigen Mac-1. Single-cell FMF cloning of these subpopulations showed that Mac-1+ cells were derived from Mac-1- cells and that these Mac-1+-cloned cells further differentiated into cells with phenotypic and functional characteristics of mature macrophages. PMID- 3088205 TI - Variable region sequences of murine IgM anti-IgG monoclonal autoantibodies (rheumatoid factors). A structural explanation for the high frequency of IgM anti IgG B cells. AB - The nucleotide sequences of heavy and light chains from 10 monoclonal IgM anti IgG1 (RF) antibodies were determined and reported here as translated amino acid sequences. Only three families of VK light chains were used in these antibodies: VK1 (two examples), VK8 (three examples), and VK19 (four examples). This represents a significant nonrandom selection of light chains. In contrast, all other variable region gene segments (i.e., VH, DH, JH, and JK) were used in a pattern consistent with random selection from the available pool of germline genes. In two cases, the same anti-IgG1 specificity was generated by a combination of very homologous light chains with unrelated heavy chains. We infer from this that the light chain is the segment used by these antibodies to bind IgG1. The nature of these sequences provides an explanation for the curious observation that as many as 15% of splenic B cells in normal mice may be expressing IgM anti-IgG; if, as our data suggest, certain light chains in combination with many different heavy chains can be used in assembling the anti IgG specificity, then, because of combinatorial association in which the heavy chain is not relevant for specificity, the fraction of IgM-producing B cells expressing these light chains should approximate the fraction of B cells making IgM anti-IgG. We calculate, based on data presented in several other studies, that 5-17% of B cells express one of the VK types observed in monoclonal RF. This agrees well with estimates for the number of B cells making IgM anti-IgG. In addition, our findings could rule out other explanations of the high percentage of B cells making RF, such as constant stimulation by antigen or presence of numerous antigenic epitopes since it was shown that IgM anti-IgG1 antibodies are not somatically mutated and that they are structurally homogeneous. We aligned the VK sequences of the RF in hopes of finding some primary sequence homology between the represented VK families which might point to residues involved in the binding interaction. Although we found no such homology in the hypervariable regions, we did find significant and unexpected homology in the FR2 and FR3 of these light chains. We noted that these regions are exposed in the Ig structure and postulate that they may be involved in a unique type of binding interaction between two Ig family domains, i.e., VK binding to a constant region domain of IgG. PMID- 3088207 TI - A new HLA-linked T cell membrane molecule, related to the beta chain of the clonotypic receptor, is associated with T3. AB - The 38 kD molecule is noncovalently associated with beta 2 microglobulin (beta 2m)-free HLA heavy chain-like molecule, and thus forms a second heterodimer distinct from the clonotypic alpha/beta T cell receptor expressed by the same clone of leukemia cells. This second heterodimer (38 kD/HLA) is variably expressed and appears to be associated with the T3 molecule. We suggest, therefore, that it has a functional role in T cell activation. PMID- 3088211 TI - Effects of octopamine, dopamine, and serotonin on production of flight motor output by thoracic ganglia of Manduca sexta. AB - Effects of biogenic amines on a centrally generated motor pattern in Manduca sexta were examined by pressure injecting nanomole to micromole amounts of octopamine, dopamine or serotonin into thoracic ganglia. Motor output was recorded extracellularly from a pair of antagonistic flight muscles and their motor neurons. The monoamines were found to alter production of a motor pattern that produces rhythmic wing flapping (10 Hz) and exhibits phase relationships similar to those in the flight pattern of intact moths. In mesothoracic ganglia with sensory nerves intact, octopamine (4 X 10(-9) mol) injected into lateral regions evoked regular firing of a single motor neuron, whereas a higher dose (4 X 10(-8) mol) often elicited the flight motor pattern. In the absence of sensory input, these doses of octopamine had little effect. Low doses (10(-10) mol) greatly enhanced motor responses to electrical stimulation of a wing sensory nerve. Dopamine (2 X 10(-10) mol) injected into the medial region of the mesothoracic ganglion elicited the flight motor pattern in the presence or absence of sensory input. Rhythmic output induced by dopamine (5 X 10(-10) mol) was suppressed by injecting serotonin (5 X 10(-10) mol) into the same region. These findings demonstrate that dopamine, octopamine, and serotonin have different effects on motor output in Manduca and suggest that these amines are involved in initiating, maintaining and terminating flight behavior, respectively. Octopamine may elicit flight production by enhancing the efficacy of sensory transmission thereby increasing excitability or arousal. Dopamine may act on interneurons involved in generating the flight motor pattern. PMID- 3088209 TI - A human monoclonal macroglobulin with specificity for alpha(2----8)-linked poly-N acetyl neuraminic acid, the capsular polysaccharide of group B meningococci and Escherichia coli K1, which crossreacts with polynucleotides and with denatured DNA. AB - We have described an IgM antibody from a patient with macroglobulinemia specifically reacting with poly-alpha(2----8)N-acetyl neuraminic acid (NeuNAc) the capsular polysaccharide of two important human pathogens, group B meningococcus and E. coli K1. This antibody has a narrowly defined specificity in its interactions with polysaccharides, being unable to bind poly-alpha(2--- 9)NeuNAc or alternating poly-alpha(2----8)alpha(2----9)NeuNAc. However, it shows interesting crossreactivity with seemingly unrelated polynucleotides and denatured DNA, supporting the hypothesis that charged groups with a given spacing may determine the specificity of antigen-antibody interactions on otherwise dissimilar molecular structures. Despite the crossreactivity with denatured DNA and polynucleotides, the antibody does not appear to have adverse effects in the patient. The antibody protects newborn rats against E. coli K1 infection, as well as the standard horse antiserum H46, and one would expect it to prove useful in humans as an adjunct to antibiotic therapy in infections with group B meningococcus and E. coli K1. We have attempted to clone the antibody-producing cells from peripheral blood, and have shown that the relevant cells are present and can be cultured. PMID- 3088212 TI - Immunohistochemical localization of chondroitin sulfate in normal and pathological human muscle. AB - The immunohistological localization of chondroitin sulfate (CS) has been studied in normal and pathological human muscle. The bovine nasal cartilage proteoglycan digested with chondroitinase ABC (BNC-PG-Ch ABC) has been utilized for the production of a rabbit polyclonal antiserum. In vitro studies showed that the antiserum binds to the unsaturated disaccharide that remains attached to the core protein after digestion of the CS chains with chondroitinase ABC (Ch ABC). As the disaccharide is created specifically by Ch ABC digestion of the CS chains, the antiserum allows the immunolocalization of CS on tissue sections digested with Ch ABC. The immunohistochemical study on normal and pathological muscle demonstrated a localization of CS in all the extracellular structures: endomysium, perimysium, muscle spindle capsule and intrafusal space. In pathological conditions, the CS was raised in all the cases with increased connective tissue, showing a pattern comparable to that obtained with fibronectin and collagen III. None of the pathological conditions displayed any peculiar character of CS distribution. This finding does not support a primary role for CS in the pathogenesis of muscular dystrophy. PMID- 3088210 TI - Properties of muscle phosphorylase b from a hagfish, Paramyxine atami. AB - Phosphorylase b was purified to homogeneity from the muscle of a hagfish (Paramyxine atami), as judged by electrophoretic and immunological criteria. The purified enzyme was partially but not fully activated by AMP, and its conversion into the a form resulted in a three-fold increase in activity. The enzyme was stimulated by SO4(2-), and kinetic experiments showed that SO4(2-) markedly increased the affinity of enzyme toward substrates: in the presence and absence of 0.35 M SO4(2-), the apparent Km values of hagfish phosphorylase b were 0.04 and 1.3% for glycogen, 8.7 and 66 mM for glucose 1-phosphate, and 0.05 and 1.0 mM for AMP, respectively. Electrophoretic and immunological data indicated that the hagfish possessed a single molecular form of phosphorylase, like the lamprey. Some immunological relatedness between the hagfish enzyme and the enzyme from lamprey or skate was demonstrated. PMID- 3088208 TI - Double isotype production by a neoplastic B cell line. II. Allelically excluded production of mu and gamma 1 heavy chains without CH gene rearrangement. AB - In our accompanying paper, we described a switch variant (BCL1.2.58) that expresses membrane and secreted forms of IgM and IgG1. Both IgM and IgG1 share the same idiotype and use the same VDJ rearrangement. Here, a detailed Southern blot analysis of the entire constant region of the Ig heavy chain (Ig CH) locus of parental (BCL1.B1) and variants (BCL1.B2) DNA showed no detectable rearrangement. Similar analysis of the JH-C mu region led to the conclusion that two heavy chain alleles present in the IgM/IgG1-producing variants carried the same VDJ rearrangement but differed in their 3' flanking regions. One chromosome 12 did not carry any Ig CH genes, whereas, the other chromosome 12 carried one copy of CH genes. In BCL1.B1, however, each of the chromosome 12 alleles carried a full copy of CH genes. Karyotypic analysis confirmed the presence of two translocated t(12;16) chromosomes in both BCL1.2.58 and BCL1.B1 cells, with a break 5' to the VH locus at the distal region (12F2) of chromosome 12, and at the proximal region below the centromere (16B3) of chromosome 16. We conclude that double production of IgM and IgG1 in BCL1.B2 is accomplished by transcription of the corresponding CH genes in germline configuration using a single VDJ on the same chromosome 12. PMID- 3088213 TI - Immunohistochemical distribution of glial fibrillary acidic protein, neurofilament polypeptides and neuronal specific enolase in the human cerebellum. AB - The human normal cerebellar cortex has been investigated using paraffin-embedded sections and a panel of antibodies against GFAP, NSE, NF 70 Kd and 200 Kd triplet proteins. The study has shown that: antiserum to GFAP labelled all and only astroglial elements; antibodies to NSE, NF 70 Kd and 200 Kd stained the perikaryon of all neurons, with two noticeable exceptions: Purkinje cells, which remained unresponsive to all 3 reagents, and basket cells which only became labelled with the NSE antiserum; the staining of dendrites and axons was exquisitely selective with both the NF and the NSE antibodies, each of which displayed unique binding patterns. These immunohistochemical features, first to be described in man, are compared with those so far reported in rodents. PMID- 3088214 TI - Neurofibromatosis xenografts. Contribution to pathogenesis. AB - We transplanted Schwann cells of 3 patients with neurofibromatosis from neurofibromas, sural nerve, and from a malignant schwannoma into sciatic nerves of immunoincompetent mice. Three and six months later, the grafts and distal nerve segments contained normal myelinated fibers. After rendering host animals immune competent again, neurofibroma and malignant schwannoma Schwann cells were rejected, but grafts retained normally myelinated fibers indicating that these were of mouse origin. Sural nerve Schwann cells from a neurofibromatosis patient were rejected also leaving naked axons in the grafted segments showing that human Schwann cells from the sural nerve of one patient had invested and myelinated the regenerating mouse axons. The nature of putative signals passing between axons and Schwann cells might be elucidated by the combination of human and animal cells in immunoincompetent host nerves. Hypothetical signals for myelination of mouse axons were normally received by sural nerve Schwann cells of a patient with neurofibromatosis, but not by Schwann cells from neurofibromas or malignant schwannomas. PMID- 3088215 TI - Modulation in vitro of immune parameters in homosexual males with the preclinical complex of symptoms related to acquired immune deficiency syndrome by azimexon. AB - In search of potential therapeutic agents for the acquired immunodeficiency syndrome (AIDS) among homosexual males, we studied in vitro the immunorestorative effect of azimexon in patients with this syndrome. Since a reduction in the ratio between helper inductor and suppressor/cytotoxic T-cell subsets (OKT-4/OKT-8) seems to be the hallmark of the syndrome, we measured azimexon-induced numerical changes in T-cell subsets and correlated them with changes in a simultaneously tested T-cell function as measured by the xenogeneic local graft-versus-host reaction (GVHR). Following incubation of peripheral blood mononuclear cells from 10 homosexual subjects with 10 micrograms/ml of azimexon at 37 degrees C for 1 h, the median number of T cells defined by the OKT-8 phenotype declined from 0.6 X 10(3) to 0.33 X 10(3)/mm3 (p less than 0.02), resulting in an increase in the OKT 4/OKT-8 ratio from 0.65 to 1.37 (p less than 0.01). There were no numerical changes in T cells defined by OKT-3 and OKT-4 phenotypes. Similar decreases in OKT-8-defined T cell occurred among eight heterosexual controls. The restoration of the OKT-4/OKT-8 ratio among the homosexual subjects was associated with a significant improvement in their T-cell function. Thus, the median volume of the local GVHR increased from 38.2 to 63.5 mm3 (p less than 0.02). Parallel changes in OKT-4/OKT-8 ratio and changes in local GVHR following incubation with azimexon were observed. These results suggest that azimexon may be an important immunorestorative agent. Clinical trials with this agent in patients with AIDS or its preclinical complex of symptoms seem warranted. PMID- 3088216 TI - Meningio-angiomatosis: a report of six cases with special reference to the occurrence of neurofibrillary tangles. AB - We report six cases of meningio-angiomatosis, a disorder of the cerebral cortex of probable malformative origin frequently associated with neurofibromatosis and either asymptomatic or associated with a seizure disorder. The patients, three males and three females, ranged from 10 to 70 years of age at diagnosis. The lesion was an incidental autopsy finding in two patients; four subjects had a seizure disorder which improved following surgical resection of the cortical lesion. In five instances the process was unifocal; one patient with neurofibromatosis had multifocal involvement. Grossly, the lesions were firm, sharply demarcated, transcortical plaques with leptomeningeal calcifications in five cases. The cortical plaques showed characteristic features of meningio angiomatosis, i.e. a circumscribed, proliferating microvasculature with perivascular meningothelial cell proliferation and fibrosis. In five cases Alzheimer's neurofibrillary change in neurons was present both within the plaques and in the surrounding cortex. Neither senile plaques nor granulovacuolar degeneration were noted. Electron microscopy in one case demonstrated typical intraneuronal accumulations of neurofilaments with regular constrictions. Intracortical vessels lined by endothelial cells with tight junctions were surrounded by pericytes and meningothelial cells. The significance of neurofibrillary tangles described in a variety of disorders, and the factors stimulating their production in the present cases are unknown. PMID- 3088217 TI - Effect of hypoglycaemia, TRH and levodopa on plasma growth hormone, prolactin, thyrotropin and cortisol in Parkinson's disease before and during therapy. AB - Thirteen drug-free and not severely affected patients with idiopathic Parkinson's disease underwent an insulin-hypoglycaemia test, a TRH test and a levodopa test. The responses of growth hormone, prolactin, cortisol and thyrotropin were measured, and retested under stable therapy with levodopa and benserazide. Mean basal and stimulated hormonal concentrations were in the normal range before and during therapy. Minor abnormalities were observed in individual cases, but did not indicate a hypothalamic dopamine deficit. PMID- 3088218 TI - Tocainide and myotonic dystrophy. PMID- 3088220 TI - Combined modality treatment of cutaneous T cell lymphoma: results of a 6-year follow-up. AB - Thirty-nine patients with cutaneous T cell lymphoma (CTCL; including mycosis fungoides or the Sezary syndrome) with no previous treatment other than topical therapy or oral corticosteroids, received total skin electron beam irradiation (TSEB) and either sequential or simultaneous systemic chemotherapy. Median follow up, measured from the time of initiation of therapy to the time of analysis, is in excess of 6 years and extends to 100+ months. Thirteen patients with stage I disease (limited to skin with no adenopathy) received 3,000 rad total skin electron beam irradiation followed by three 2-week courses of daily intravenous (IV) mechlorethamine. Twenty-six patients with advanced disease (stage II-IV) received 2,400 rad of TSEB and simultaneous chemotherapy with two alternating three-drug regimens: vinblastine, doxorubicin, and bleomycin (VAB) alternating with cyclophosphamide, methotrexate, and prednisone (CMP) administered over 54 weeks. The overall response rate was 92% with 16 of 39 patients (41%) achieving a histologically documented complete response (CR). Stage I patients had a significantly increased CR rate (77%) compared with stage II-IV (P less than .01). The overall 6-year survival was 92% for stage I patients and 26% for stage II-IV patients (23%) (P less than .001). Among ten completely responding stage I patients, six remain alive and disease-free in excess of 72 months. The median disease-free survival is 26 months for completely responding stage II-IV patients (P = .04), but none are continuous disease-free survivors after protocol treatment. We conclude that combined modality treatment can be safely administered and produces prolonged disease-free survival in some stage I patients, but not in more advanced stage patients. PMID- 3088219 TI - Random prospective study of vindesine versus vindesine plus high-dose cisplatin versus vindesine plus cisplatin plus mitomycin C in advanced non-small-cell lung cancer. AB - In this phase III randomized study, 124 evaluable patients with unresectable non small-cell lung cancer (NSCLC) were randomized to vindesine v cisplatin (120 mg/m2) plus vindesine v cisplatin (60 mg/m2) plus vindesine plus mitomycin C. The objective response rate for cisplatin and vindesine was 27% v 20% for cisplatin, vindesine, and mitomycin C, and 14% for vindesine alone (P = .25 for cisplatin and vindesine v vindesine). The percentage of patients having stable disease (no progression for a minimum of 3 months) was 20% (cisplatin and vindesine), 27% (cisplatin, vindesine, and mitomycin C), and 26% (vindesine alone), respectively. The median survival time for vindesine was 18 weeks, compared with 26 weeks for cisplatin and vindesine and 17 weeks for cisplatin, vindesine, and mitomycin C. Overall survival was not statistically different for cisplatin plus vindesine v vindesine (P = .65). There was no evidence for improved duration of remission or survival of responders with the cisplatin (120 mg/m2) and vindesine arm. This study failed to demonstrate sufficient therapeutic benefit for cisplatin and vindesine (+/- mitomycin C) compared with single-agent vindesine to justify the increased cost and toxicity of these combination regimens. PMID- 3088221 TI - Phase I study of multiple dose intramuscularly administered recombinant gamma interferon. AB - We report the results of a phase I study of the tolerance and biologic activity of intramuscularly (IM)-administered recombinant interferon-gamma (rIFN-gamma). Forty-four patients with metastatic cancer were given rIFN-gamma at doses ranging from 0.01 to 2.5 mg/m2/d for 42 days. The most common side effects were fever, flulike symptoms, night sweats, and granulocytopenia. The maximum tolerated dose was 0.5 mg/m2/d. Administration of rIFN-gamma resulted in modulation of immune system functions, including induction of major histocompatibility complex associated antigens on blood leukocytes, an increase in blood surface immunoglobulin-bearing B cell and natural killer (NK) cell number, and NK cell cytotoxicity. Serum lysozyme, determined as an estimate of tissue macrophage activity, also increased. Serum assays for anti-interferon antibodies were negative in all patients. Five of eight evaluable patients with lymphoproliferative disorders showed objective evidence of tumor regression consisting of partial responses (two patients), and minor responses (three patients). These data suggest that further phase II studies of IM-administered rIFN-gamma are indicated. PMID- 3088222 TI - Chiasmal gliomas: appearance and long-term changes demonstrated by computerized tomography. AB - A survey of 22 cases showed the broad spectrum of lesions collectively termed "chiasmal gliomas." Three computerized tomography (CT) patterns were diagnostic: a tubular thickening of the optic nerve and chiasm, a suprasellar tumor with contiguous optic nerve expansion, and a suprasellar tumor with optic tract involvement. Globular suprasellar tumors lacking these features required a histological examination for diagnosis. Tumor growth was documented by CT in only three chiasmal gliomas; all were the globular type. Failing visual function did not reflect chiasmal tumor growth, and stable vision did not exclude it. Both patients with tubular optic nerve thickening and two of three patients with unilateral optic nerve expansion had neurofibromatosis. Five tumors became smaller after irradiation. Complications of radiation therapy included calcification of lenticular nuclei and remote infarcts. In patients who underwent biopsy, the CT appearance did not differentiate juvenile pilocytic astrocytoma from anaplastic astrocytoma. Thus, CT guides the diagnosis and neurosurgical treatment of chiasmal gliomas, establishing the need for biopsy or ventricular shunting. PMID- 3088223 TI - Three-phase white blood cell scan: diagnostic validity in abdominal inflammatory diseases. AB - Indium-111-oxine saline-labeled "mixed" leukocyte (n = 16) and "pure" granulocyte (n = 66) scans were prospectively performed as "three-phase" white blood cell (WBC) scans (imaging: 30 min, 4 hr, and 24 hr after reinjection of the cells) in 82 patients suspected of having abdominal or retroperitoneal abscesses or inflammatory lesions. Inflammation was verified histologically, endoscopically, radiologically or by autopsy in 51 and excluded in 31 patients. Sensitivity, specificity, and diagnostic accuracy of the 30-min scan (90%, 56%, 72%) were statistically significantly lower than the 4-hr scan (96%, 97%, 98%). Of the 24 hr scan sensitivity, specificity, and diagnostic accuracy were only 84%, 98%, and 89% because many patients with chronic inflammatory bowel diseases had excreted a portion of intestinal 111In activity by 24 hr. The overall sensitivity, specificity, and accuracy of the "three-phase" WBC scan were 98%, 97%, and 98%, respectively. Only one female patient showed a false-positive scan with granulocyte uptake in an ulcerating adenocarcinoma of the colon. The 4-hr scan or the three-phase study are recommended because of their high sensitivity, specificity, and excellent diagnostic accuracy (98%). The 30-min scan is less specific (56%); the 24-hr scan less sensitive (84%). The three-phase study additionally allows the differentiation between inflammatory bowel diseases and abscesses because it allows observation of granulocyte kinetics for 24 hr. PMID- 3088225 TI - Pediatric radiation dose from [111In]leukocytes. PMID- 3088224 TI - Evaluation of mathematic models to assess platelet kinetics. AB - Twelve mathematic methods used to calculate the mean platelet survival time were compared by determining the "goodness of fit" of the models to the platelet survival curves of 15 reference subjects and 54 patients. Platelets were labeled with [111In]oxine. The linear (LN), exponential, weighted mean, multiple hit (MH), Dornhorst (DH), Meuleman (ML), alpha order (AO), and polynomial (PO) mathematic models were investigated. The goodness of fit for the exponential model was determined by the nonlinear least squares method (EP), and also by the linear least squares method on logarithmically transformed data (EX) as is recommended. The modified weighted mean (MWM) and the usual weighted mean method (WM) obtained with these exponential models were tested. The Dornhorst (DH10) and Meuleman (ML10) models, where the potential age-dependent platelet survival times were kept constant at 10 days, were also evaluated. The goodness of fit results, expressed as % s.d. indicated that the LN (5.2%), EX (5.0%), EP (4.4%), WM (3.7%), DH10 (3.7%), and ML10 (3.7%) models all fitted the data significantly worse than the MWM, MH, DH, ML, AO, and PO models (range 3.2-3.3%). The mean platelet survival time determined with the MH model differed significantly from the results with the DH, ML, and AO models. The results of mean platelet survival time calculated with different mathematic models cannot, therefore, be compared directly. The models that fitted the platelet survival curve well varied slightly in sensitivity to noise as is indicated by the coefficient of variation of the mean platelet survival time estimates for the reference subjects (range 7.9 12.0%). Fitting data to at least two mathematic models has definite advantages. Data on which the calculations are based are probably invalid if the following are true: (a) if the mean platelet survival time estimated with the alpha order model is shorter than that estimated with the EP, MWM, or MH models, or (b) the mean platelet survival time estimated with either the DH, ML, AO, or PO models, is longer than the LN, MWM, or MH estimate of the mean platelet survival time. We conclude that the mean platelet survival time can be reliably estimated by fitting the data to either the MWM method (if limited computing facilities are available) or the MH model. Confidence in the result will be increased if considered in conjunction with the finding obtained with one other model; in those cases where the platelet survival time is very short, the alpha order model is recommended.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3088226 TI - Effects of dietary triglycerides on serum and liver lipids and sterol excretion of rats. AB - The effects of several highly purified simple and mixed dietary triglycerides (TGs) on serum and liver cholesterol and on sterol excretion were studied in rats. The TGs contained 4- to 18-carbon fatty acids with melting points of -75 to 63.5 degrees C. Ratios of polyunsaturated to saturated fatty acids ranged from 0.1 to 105. Ratios of total unsaturated to saturated fatty acids ranged from 0.1 to 115. All diets contained 8% TG plus 0.82% safflower oil. Sterols were quantified directly by a new and improved high resolution gas chromatographic method and were identified by mass spectrometry. TG digestibilities correlated negatively with melting points above 30 degrees C (R = -0.9). Serum cholesterol was lower in rats fed tributyrin, tricaproin, tricaprylin, tricaprin, trielaidin, trilinolein or partially hydrogenated soybean oil (43-49 mg/dl) than in those fed trilaurin, trimyristin, tripalmitin, tristearin, triolein or corn oil (54-59 mg/dl). Liver lipid levels correlated (R = 0.65) with the degree of unsaturation of dietary TGs. Liver cholesterol levels correlated negatively with fecal excretion of coprostanol plus cholesterol (R = -0.4). Coprostanol plus cholesterol excreted in feces correlated weakly (R = 0.3) with intake of total sterol and of polyunsaturated TGs (R greater than or equal to 0.4 are at least 80% significant). The results demonstrate that consumption of polyunsaturated TGs was associated with higher hepatic lipid levels. Also, greater fecal excretion of coprostanol plus cholesterol was associated with lower hepatic cholesterol levels. PMID- 3088227 TI - Response of rats to diets of equal chemical score: effect of lysine or threonine as the limiting amino acid and of an amino acid excess. AB - The effect of lysine or threonine deficiency with or without excesses of all other amino acids was evaluated in a 21-d feeding study with male rats. Four amino acid mixtures were designed to be first limiting for the rat in lysine or threonine and contained either 0 or 50% excess of nonlimiting amino acids. These mixtures were incorporated into purified diets to provide seven levels [20-140% of the National Research Council (NRC) requirement] of the limiting amino acid. Food intake, body weight gain and carcass composition were measured for each rat to determine the effects of the identity of the limiting amino acid and of amino acid excess on the response to dietary chemical score. Significant effects and/or interactions of the identity of the limiting amino acid (i.e., Lys or Thr) and the presence of excess amino acids were seen for each of the measured responses. At equivalent dietary percentages of the NRC requirement, threonine deficiency supported greater body weight gain than did lysine deficiency. At equivalent deficiencies (Lys vs. Thr) threonine-deficient rats were more susceptible to adverse effects of excess amino acids. When the limiting amino acids were incorporated into the diet through incremental addition of the deficient amino acid mixture, rats responded to levels of lysine or threonine in excess of the NRC requirement. These results suggest that the current NRC requirements for these amino acids are too low and that aspects of the dietary amino acid composition other than the percentage deficit of the limiting amino acid can be important determinants of animal response. PMID- 3088228 TI - Digestibility and utilization of protein and energy from Nasha, a traditional Sudanese fermented sorghum weaning food. AB - Whole grain sorghum flour was fermented into Nasha, a traditional Sudanese food, and freeze-dried or drum-dried. It was cooked and fed to convalescent malnourished infants and small children as 61% of total diet calories and all of 6.4% protein calories, with (Lys+) and without lysine supplementation to 3% of protein. Apparent absorptions of nitrogen were 73 +/- 5 and 74 +/- 6% of intake, significantly (P less than 0.01) less than those from preceding (Cas-1, 86 +/- 3%) and following (Cas-2, 85 +/- 3%) isonitrogenous casein diets. Apparent retentions of nitrogen from Nasha (26 +/- 10%) were significantly lower than those from Lys + (34 +/- 9%, P less than 0.05), Cas-1 (35 +/- 11%, P less than 0.01) or Cas-2 (49 +/- 9%, P less than 0.01). Retentions from Cas-2 were higher than those from Cas-1 or Lys + (P less than 0.01). Fecal wet and dry weights were higher (P less than 0.02) during both Nasha diets and Cas-2 than during Cas-1. Fecal energy and carbohydrate were significantly (P less than 0.01) higher from either Nasha diet than from either casein diet; fecal fat was not different. Two children received drum-dried Nasha without further cooking; digestibilities were not different from those of the cooked product but biological value was much lower. When properly cooked and consumed along with small amounts of a good source of lysine, Nasha is a satisfactory weaning food. PMID- 3088230 TI - Spirometric findings in capacitor workers occupationally exposed to polychlorinated biphenyls (PCBs). AB - Spirometric findings (forced vital capacity [FVC], forced expiratory volume at one second [FEV1], FEV1/FVC) in a population of capacitor workers with occupational exposure to polychlorinated biphenyls (PCBs) are described during active PCB use (1976) and following the PCB ban (1979 and 1983). The initial finding of restrictive impairment (16%) in 1976 was not supported by chest roentgenogram findings, nor confirmed in 1979 and 1983, and was interpreted as artifactual due to test operator inexperience and inadequate expiratory efforts. Obstructive impairment was consistently found in 15% of the total population in 1976 and 1979. A history of respiratory illness and/or symptomatology and reduced FEV1/FVC was correlated with PCB exposure and serum PCB levels (lower homologs) in females in 1976, but not in males. Smoking was correlated with reduced FEV1 values. No correlation of spirometric variables with past exposure or serum PCB levels was found for either sex in 1979. PMID- 3088229 TI - Effect of dietary cystine on methionine metabolism in rat liver. AB - Cystine supplementation of adequate diets resulted in significantly higher hepatic levels of betaine-homocysteine methyltransferase. Other changes occurred but were a function of the basal diet. When the latter contained 0.25% methionine + 0.5% cystine, the additional cystine caused a markedly lower hepatic cystathionine synthase activity and lower levels of both adenosylmethionine and serine. The metabolic effect of these changes may be enhanced methionine retention and diminished transsulfuration. PMID- 3088231 TI - Effect of levamisole in inhibition of DMBA carcinogenesis. PMID- 3088232 TI - Immunohistochemical observations on carbonic anhydrase I and II in human salivary glands and submandibular obstructive adenitis. AB - Immunohistochemical identification of carbonic anhydrase I and II (CA-I, CA-II) was made in human major salivary glands and obstructive adenitis in submandibular glands. Normal salivary glands stained the strongest for CA-II in serious acinar cells and were negative in mucous cells. Moderate to strong staining for CA-I and CA-II was found in ductal segments. Submandibular glands with obstructive adenitis exhibited reduced CA-I activity in atrophic acinar cells, but not in ductal elements in the early and intermediate stages of the disorder. In the late stage of the obstructive lesion, CA staining in duct-like structures was moderate; however, almost degenerate ductal cells were negative for CA. During the progression of the degeneration in the obstructive lesion, the CA staining decreased dependent on acinar atrophy. Even after longstanding obstruction of the salivary gland, altered ductal epithelia may retain some of their functions. PMID- 3088233 TI - Expression of class I and class II major histocompatibility complex antigens on epithelial cells in recurrent aphthous stomatitis. AB - The concept of an immunopathogenesis in the establishment and progression of the recurrent aphthous stomatitis (RAS) lesion is well accepted. In this study the expression of Class I and Class II major histocompatibility complex (MHC) antigens on the epithelial cells in the preulcerative, ulcerative and healing phases of RAS lesions was investigated using monoclonal antibodies in an immunohistological technique. Both Class I and Class II MHC antigens were found on the basal cells in preulcerative lesions. As the lesions progressed to the ulcerative phase, antigen expression occurred on the cell membranes throughout the entire thickness of the epithelium. With healing, the expression of both Class I and Class II MHC antigens on epithelial cells declined to a stage where there was little or no detectable antigen on the cell membranes. Although cytotoxicity of epithelial cells in RAS lesions is accepted, the role of MHC antigen expression on these cells is uncertain and remains to be ascertained. Nevertheless, the results of the present study indicate that MHC antigens are expressed by epithelial cells in RAS and their expression follows a defined sequence. PMID- 3088234 TI - Pulpal response to an experimental adhesion promoter. AB - The pulpal response to an experimental adhesion promoter (PTP) used in conjunction with a composite resin material, Biogloss, is described, in lined and unlined cavities. Dycal was the lining and negative control material. Standardised Class V cavities were prepared in ferret canine teeth and the pulpal responses studied after 1, 2 and 4 weeks and 6 months post-operatively. Pre treatment of cavities with PTP causes a reduction in pulpal inflammation at 7 and 14 days compared with Biogloss. There was no obvious difference at the longer time intervals. Pre-treatment with PTP delays the ingress of microorganisms at the cavity wall/material interface but does not prevent it in the long term in this situation. The effect of PTP is not altered if the fluid is allowed to dry naturally rather than by blow drying. PMID- 3088235 TI - Immunodetection of involucrin in lesions of the oral mucosa. AB - The immunoperoxidase method for involucrin detection was applied to the study of the maturation of epithelial lesions of the oral mucosa that included specimens of leukoplakia, lichen planus, verrucous carcinoma, carcinoma in situ and invasive carcinoma. Areas of orthokeratinized, parakeratinized, and non keratinized normal mucosa were also studied. Normal orthokeratinized epithelia showed intracytoplasmic or pericellular staining in the suprabasal epithelial layers in a pattern similar to that of the normal epidermis. Parakeratinized and non-keratinized epithelia were less stained. Intense staining was observed in leukoplakia, whereas the staining of lichen planus was less intense but exhibited a more homogeneous pericellular staining pattern than leukoplakia. Verrucous carcinoma was markedly and very irregularly stained. Carcinomas in situ and invasive carcinoma exhibited a slightly positive and patchy reaction. The distribution patterns of involucrin in the lesions correlated very well with the degree of epithelial differentiation. In addition, irregular patchy distribution correlated with the degree of atypia, and was especially evident in carcinomas. PMID- 3088236 TI - Angular cheilitis: a clinical and microbial study. AB - The purpose of this prospective study was to re-examine the relative importance of various factors in the pathogenesis of angular cheilitis. Sixty-four patients with cheilitis were examined clinically and microbiologically. In addition, a subsample of 23 patients was examined for serum iron and transferrin. The clinical appearance of the lip lesions fell into 4 categories. A ground rhagad at the corner of the mouth involving adjacent skin, was the most frequent type among dentate patients, whereas among denture wearers a deep lesion following the labial marginal sulcus was frequently observed. Dentate patients and denture wearers with cheilitis often had atopic constitution or cutaneous diseases. Pathogenic microorganisms were cultured from the lesions in all 64 patients; Staphylococcus aureus in 40 patients and Candida albicans in 45. The results of this study indicate a correlation between angular cheilitis and pathogenic microorganisms. Furthermore, among dentate patients, a correlation exists between cutaneous discomfort and angular cheilitis. Other etiological factors suggested for this disorder were found to be of subordinate importance. PMID- 3088237 TI - Indirect immunofluorescence of oral lichen planus. AB - Sections of lesional tissue from 6 patients who exhibited only oral lesions of lichen planus (LP) were incubated with autologous serum and studied immunopathologically for the presence of lichen planus specific antigen (LPSA). None of the specimens was positive for LPSA. Serum from the oral LP patients was subsequently incubated with allogeneic cutaneous LP lesional tissue sections, which resulted in the demonstration of LPSA in 2 of the 4 sera examined. These results suggest an immunologic relationship between cutaneous LP and at least some cases of oral LP. PMID- 3088238 TI - Interleukin 2: its role in the proliferation of neoplastic T and B cells. PMID- 3088239 TI - An approach to the molecular mechanisms of cancer induction. PMID- 3088240 TI - Renal handling of carnitine in children with carnitine deficiency and hyperammonemia associated with valproate therapy. AB - Free and acylcarnitine in serum and urine samples were measured in five patients with hyperammonemia associated with anticonvulsant therapy including sodium valproate, of whom three had a Reye-like syndrome. All had considerable reduction in serum free carnitine and slight increase of acylcarnitine concentrations, suggesting increased conversion of free to acylcarnitine by valproate administration. Urinary excretion of both free and acylcarnitine was increased, accompanied by depressed reabsorption of free carnitine and decreased acylcarnitine/free carnitine clearance ratio. These results indicate a decreased threshold for free carnitine. The combination of these several factors may be responsible for carnitine deficiency in patients with hyperammonemia taking valproate. PMID- 3088241 TI - Treatment of persistent pubertal gynecomastia with dihydrotestosterone heptanoate. AB - Four boys with persistent pubertal gynecomastia were given intramuscular dihydrotestosterone heptanoate (DHT-hp) at 2 to 4-week intervals for 16 weeks. By the end of treatment, breast size in all four boys had decreased 67% to 78%. Initial plasma levels of gonadotropins, estradiol, testosterone, and dihydrotestosterone (DHT) were normal. Mean plasma DHT concentration rose with the injections of DHT-hp, and remained elevated throughout the treatment period. Estradiol, LH, FSH, and testosterone decreased during treatment, as did 24-hour urinary LH and FSH. No regrowth of breast tissue was observed 6 to 15 months after treatment, although hormone concentrations had returned to near pretreatment values by 2 months after the last injection. DHT-hp has potential to be an effective medical therapy for persistent pubertal gynecomastia. PMID- 3088242 TI - Risk factors for development of bacterial meningitis among children with occult bacteremia. AB - To identify risk factors for the development of bacterial meningitis, we compared clinical characteristics in children with occult bacteremia who did and those who did not subsequently develop bacterial meningitis. The estimates of risk were adjusted for the possible confounding effects of other characteristics by using logistic regression. Of 310 children (median age 15 months) who had occult bacteremia with Streptococcus pneumoniae, Haemophilus influenzae type b, or Neisseria meningitidis at either Yale-New Haven Hospital or Children's Hospital of Pittsburgh, bacterial meningitis subsequently developed in 22 (7%). Compared with the risk associated with occult bacteremia with S. pneumoniae, the adjusted relative risk for bacterial meningitis was 85.6 (P less than 0.0001) and 12.0 (P = 0.0001) for N. meningitidis and H. influenzae type b, respectively. By contrast, the adjusted relative risk associated with a lumbar puncture at the initial visit was only 1.2 (P = 0.78). The development of bacterial meningitis in children with occult bacteremia is strongly associated with the species of bacteria that causes the infection, but not with a lumbar puncture or with other clinical characteristics identifiable at the initial visit. PMID- 3088244 TI - Interventions for premature infants. PMID- 3088243 TI - Anorexia nervosa, athletics, and amenorrhea. AB - We examined menstrual function in two groups of patients meeting the DSM III criteria for anorexia nervosa who differed only in their physical activity. Sixteen athletes with anorexia nervosa were compared with eight sedentary patients who had anorexia nervosa. Athletic patients with anorexia were found to have lower gonadotropin levels, a longer period of amenorrhea both before significant weight loss and after weight rehabilitation, and a higher weight at the time of resumption of menses than patients with anorexia who were sedentary. However, both groups were markedly undernourished, had amenorrhea before significant weight loss and after weight rehabilitation, and had lower gonadotropin levels than normal subjects. These data suggest that the increased physical activity often seen in patients with anorexia nervosa worsens, but does not cause, menstrual dysfunction. PMID- 3088245 TI - Limited dermal ossification: clinical features and natural history. AB - For 9 years we have observed a girl who has ossification in the dermis with a strikingly limited distribution. Recently a second girl with similar dermal ossification restricted to a single extremity was identified. The ectopic bone is histologically identical to normal membranous bone. These two patients have no obvious underlying cause for soft tissue bone formation, and no disorder of calcium or phosphate metabolism. Ossification first involved the dermal and subcutaneous connective tissue, and with time advanced locally in the affected areas to bridge joints and limit mobility. The ossification has now extended to involve muscle fascia but has not involved the muscle itself. This disease appears to represent a heretofore unrecognized disorder of mesenchymal differentiation. PMID- 3088246 TI - Data entry errors in computerized nutritional calculations. PMID- 3088247 TI - Maltase-glucoamylase and residual isomaltase in sucrose intolerant patients. AB - Small intestinal biopsies from nine patients with sucrase-isomaltase deficiency (sucrose-intolerance) were analyzed. All patients lacked sucrase activity and three patients had a residual isomaltase activity and a corresponding isomaltase precipitate following immunoelectrophoresis. By polyacrylamide gel electrophoresis in sodium dodecyl sulfate followed by immunoblotting the residual isomaltase appeared as a single polypeptide with molecular weight of approximately 145,000. Maltase-glucoamylase in the biopsies was specifically quantitated by crossed immunoelectrophoresis. One of the patients had an almost total deficiency of maltase-glucoamylase in the biopsy, three patients had a normal amount of maltase-glucoamylase, and five patients constituted an intermediary group. These results indicate that some of the sucrase-isomaltase deficient patients also have a more or less pronounced deficiency of maltase glucoamylase. The patients constitute an even more heterogeneous group than earlier suggested and should be classified by the amount not only of sucrase and isomaltase but also of maltase-glucoamylase. PMID- 3088248 TI - Diamine oxidase in serum and small intestinal biopsy tissue in childhood celiac disease. AB - Diamine oxidase (DAO) activities were measured in small intestinal biopsies and in serum from control children and children with florid celiac disease. Mucosal DAO activities were found to be significantly higher in control children when compared with children with celiac disease (mean +/- SEM: 486 +/- 39 versus 121 +/- 22.1 nmol h-1 g-1 wet weight, p less than 0.001). Similarly, serum DAO activities were significantly higher in control children when compared with children with celiac disease (mean +/- SEM: 39 +/- 12 versus 13.6 +/- 2 pmol h-1 ml-1 serum, p less than 0.002). The lower serum activities associated with low mucosal values support the hypothesis that serum DAO activity reflects small bowel integrity. PMID- 3088249 TI - Intestinal permeability to [51Cr]EDTA in children with cystic fibrosis. AB - Intestinal permeability was investigated in 14 children with cystic fibrosis making use of [51Cr]EDTA as probe molecule. Ten normal young adults and 11 children served as controls. After oral administration of [51Cr]EDTA, 24 h urine was collected. Urinary radioactivity was calculated and results expressed as percentage of oral dose excreted in 24 h urine. Mean and SEM were as follows: 2.51 +/- 0.21, 2.35 +/- 0.24, and 13.19 +/- 1.72 for control children, normal adults, and cystic fibrosis patients, respectively. The permeability differences between cystic fibrosis patients and either control children or control adults are significant (p less than 0.001). PMID- 3088250 TI - Persistent morbidity and mortality of protein calorie malnutrition in young infants with CF. AB - Young infants with cystic fibrosis (CF) are at risk for developing symptomatic protein-calorie malnutrition (PCM) characterized by hypoalbuminemia, edema, and anemia. We reviewed the hospital charts of all infants less than 12 months of age referred to our CF clinic between 1979 and 1982 and found nine patients with PCM (13%). Their courses were characterized by age less than 7 months (nine patients), frequent use of soy formula (eight patients), presence of gastrointestinal or respiratory symptoms before being diagnosed with CF (eight patients), severe respiratory distress often requiring mechanical ventilation (five patients), significant infections (three patients), and high mortality (five patients). We further noted that eight infants were not on pancreatic enzyme therapy at the onset of PCM. This clinical study extends the findings of earlier reports of PCM in patients with CF by showing that this syndrome persists as a major source of morbidity and mortality in young infants with CF, especially those fed soy formula and not receiving pancreatic enzyme supplements. Because PCM can develop rapidly and may be the presenting sign of CF in young infants, we speculate that early diagnosis of CF with institution of pancreatic supplements may decrease incidence and severity of PCM in young patients with CF. PMID- 3088252 TI - Fetal surgery in the primate. III. Maternal outcome after fetal surgery. AB - Maternal safety and future reproduction potential are paramount considerations in fetal surgery. In a series of 102 fetal surgical procedures on time-dated pregnant monkeys, we examined the maternal complications, the potential for future pregnancy, and the effects of uterine staples used for hysterotomy and uterine closure. There were significant maternal complications associated with the development of the present techniques for fetal surgery including 3 maternal deaths, 5 uterine ruptures, and 5 cases of wound infection of dehiscence. All were preventable with knowledge gained from this experience. Compared with a control unoperated breeding colony, fetal surgery did not interfere with subsequent reproductive capacity in animals that had uterine closure with absorbable sutures. However, metal staple hysterotomy resulted in a markedly decreased fertility rate probably related to exposure of the endometrial cavity to a permanent foreign body. Although serious maternal complications occurred in this series, many are avoidable as we improve both our obstetric management and our anesthetic and surgical techniques. Prenatal intervention carries considerable maternal risk and should not be attempted clinically under any but the most rigorous conditions. PMID- 3088251 TI - Myoinositol in small preterm infants: relationship between intake and serum concentration. AB - Serum myoinositol (henceforth called inositol) concentration was measured in 12 preterm infants (birth weight 800-1,700 g, gestational age 27-32 weeks) from birth to 10 postnatal weeks. The diet was analyzed for inositol concentration and the daily intake was correlated with serum inositol. There were striking differences in the inositol concentration of infant feedings: preterm colostrum 4.22 +/- 0.51 mM; term colostrum 2.91 +/- 0.21 mM; mature milk 1.81 +/- 0.20 mM; infant formulas 0.09-0.39 mM; parenteral nutrition 0.15 +/- 0.13 mM. The high fetal serum inositol often fell during the first 2 weeks. After 2 weeks, serum inositol correlated significantly with inositol intake (R = 0.601, p less than 0.004). On breast milk serum inositol concentrations (0.56 +/- 0.07 mM) were higher than on formula feedings (0.36 +/- 0.03 mM). Since according to animal studies inositol is important during prenatal growth and differentiation, the present data justify further study on importance of dietary inositol in preterm infants. PMID- 3088255 TI - Design and synthesis of a hapten for the radioimmunoassay of bupropion. AB - The synthesis of a hapten useful in the radioimmunoassay of bupropion is described. Since bupropion has no functional group that can be easily derivatized, a hydroxypropyl group was incorporated into the molecule. Studies in cross-reactivity with possible metabolites required the synthesis of the 4' hydroxy analogue of bupropion. This synthesis is also described. PMID- 3088253 TI - Transamniotic fetal feeding. III. The effect of nutrient infusion on fetal growth retardation. AB - The small-for-gestational age (SGA) infant resulting from intrauterine growth retardation (IUGR) is at high risk for perinatal complications and chronic morbidity. Most IUGR is the result of inadequate transfer of nutrients and/or oxygen from mother to fetus. Transamniotic fetal feeding (TAFF) has been proposed as a method of treating IUGR in which nutrients infused into the amniotic fluid would be swallowed, absorbed, and used by the growth retarded fetus. To study the efficacy of TAFF in the treatment of IUGR, we have previously described a rabbit model for TAFF that takes advantage of the relationship between "natural runting" (IUGR) and position on the uterine horn. We report on a controlled study of the effects of specific nutrient infusion on fetal growth retardation in this model. The infusion of dextrose, a dextrose-amino acid mixture, or lipid did not reverse or ameliorate fetal IUGR compared with controls. In addition, the infusion of lipid emulsion resulted in chronic lipid aspiration and further growth retardation. This work does not support the use of TAFF as a prenatal treatment for IUGR and suggests that oxygen may be the growth-limiting factor in most substrate deficiency IUGR. In addition, the infusion of solutions containing lipid may be harmful to the developing fetus. PMID- 3088254 TI - A comparison of intragastric and intrajejunal feedings in neonatal piglets. AB - Intrajejunal feedings by continuous infusion of nutrients into the proximal jejunum have been advocated for premature and low-birthweight infants. This technique eliminates the risks of gastric distention and aspiration associated with intragastric feedings. However, intrajejunal feedings disregard the normal physiologic responses to gastric feedings and completely bypass the stomach and duodenum, thus eliminating the important contributions to intestinal function of salivary enzymes, pancreatic secretions, and duodenal osmoregulation and absorption. The objective of this investigation is the comparison in neonatal piglets of differences in nutritional status and intestinal absorption between animals administered intrajejunal nutrients with those given intragastric formula. A total of 14 three- to five-day-old 1.5 to 2.5 kg domestic strain piglets were studied for two weeks. Seven animals underwent operative insertion of a jejunostomy tube into the proximal jejunum, while seven animals had a gastrostomy tube inserted. Intravenous antibiotics and fluids were given for two days postoperatively, then Premature Enfamil (24 kcal/oz) was administered continuously through the feeding tube. The animals were maintained on 115 kcal/kg/d for 10 to 14 days with daily measurements of weight, height, length, stool volume, and weekly determinations of electrolytes, blood counts, and fecal fat analysis. Student's unpaired t-test analysis of the data reveals significantly greater weight gain in the gastrostomy animals (2.5% weight gain/d +/- 0.3% v 1.5% +/- 0.3%, P less than 0.05). These animals also had less diarrhea (14% v 71%), and less fat malabsorption (0.15g/48 hr v 0.9g/48 hr).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3088256 TI - Conceptual guidelines for podiatric services in long-term care facilities. PMID- 3088257 TI - Effect of verapamil on prostaglandin E2 synthesis by hydronephrotic rabbit cortical interstitial cells in primary culture. AB - The effect of the calcium channel blocker verapamil on prostaglandin (PG) E2 production by hydronephrotic cortical interstitial cells in primary culture was investigated. Verapamil displayed a dual action, maximally enhancing PGE2 production from 1.2 +/- 0.2 to 30.7 +/- 4.3 ng/ml at 30 microM, whereas at higher concentrations the effect tapered down to base line. Stimulation of PGE2 synthesis by verapamil required extracellular calcium, but was unaffected by the intracellular calcium inhibitor 8-(Diethylamino)octyl 3,4,5-trimethoxy-benzoate or the calmodulin inhibitor trifluoperazine. Other calcium channel blockers, nifedipine and diltiazem, failed to stimulate PGE2 synthesis, implying that this effect of verapamil was unrelated to its commonly recognized action to inhibit calcium channels. However, stimulation by verapamil was inhibited by quinacrine (mepacrine), suggesting a mechanism involving activation of a phospholipase. In addition, verapamil attenuated the bradykinin- or ionophore A23187-stimulated PGE2 production, but it did not alter arachidonic acid-induced PGE2 synthesis. These observations indicate that, in addition to phospholipase activation, verapamil may also act to inhibit phospholipase activity. Inhibition was concentration-dependent over the range 3 to 300 microM, and was reversible. It is concluded that verapamil, at different concentrations, exerts a dual action on cellular phospholipase activity, thereby stimulating, and in turn inhibiting, PGE2 synthesis by hydronephrotic interstitial cells. PMID- 3088258 TI - Doxorubicin and doxorubicinol-induced alterations in human polymorphonuclear leukocyte oxygen metabolite generation. AB - The effects of doxorubicin and its primary metabolite doxorubicinol on the polymorphonuclear leukocyte (PMNL) respiratory burst were studied using lucigenin and luminol for detection of oxygen metabolite generation. Although both anthracyclines inhibited PMNL activation at concentrations achieved with therapeutic administration of doxorubicin, doxorubicinol was much more potent than doxorubicin. Preincubation of PMNL with either drug caused a persistent inhibition of cell function after drug washout that was not prevented by inclusion of either free radical scavengers or iron chelators in the incubation medium. Although complete suppression of the PMNL respiratory burst occurred with concentrations of doxorubicinol greater than 0.3 microgram/ml, a marked potentiation of the response was observed at lower concentrations (0.01 or 0.03 microgram/ml) of the same drug. Potentiation occurred only when albumin was present in the reaction medium, was eliminated by iron chelators, was not observed after PMNL incubation with drug and was dependent upon the activating agent. In contrast to doxorubicinol, doxorubicin did not potentiate the PMNL respiratory burst. These results demonstrate potent effects of doxorubicinol on PMNL oxygen metabolite generation that are markedly greater in degree and different in character than those of doxorubicin. Because both inhibitory and enhancing effects are apparent at concentrations of doxorubicinol achieved in vivo, this metabolite may be important in the clinically observed toxicity of doxorubicin. PMID- 3088259 TI - Sympathetic vasoconstriction and renin secretion cause pressor responses to thyrotropin-releasing hormone in rats. AB - To study peripheral mechanisms underlying cardiovascular responses to thyrotropin releasing hormone (TRH) we recorded the effects of i.c.v. infusions of TRH in urethane-anesthetized rats after various drug pretreatments, nephrectomy or renal denervation. TRH invariably increased blood pressure, heart rate and sympathetic nerve activity. After alpha-1 adrenergic blockade with prazosin, pressor responses to TRH were delayed in onset and reduced in magnitude. After renal denervation or pretreatment with propranolol for beta adrenergic blockade, captopril for converting enzyme inhibition or Sar1Ile8 angiotensin II for angiotensin II blockade, pressor responses to TRH were unaltered during the first few minutes but became significantly reduced thereafter. Bilateral nephrectomy inhibited markedly the whole pressor response including its onset and subsequent elevation. Consequently, initial inhibition by prazosin was considered due to removal of alpha-1 adrenergic vasoconstriction whereas the later attenuation was attributed to antagonism of the renin-angiotensin system. None of the procedures tested affected the attendant sympathetic hyperactivity, but the tachycardia was prevented by beta adrenergic blockade. These results are compatible with the interpretation that, by acting centrally, TRH stimulates sympathetic hyperactivity which then elevates blood pressure by increasing not only sympathetic vasomotor tone but also renal renin secretion. PMID- 3088260 TI - Reversal of supersensitive apomorphine-induced rotational behavior in mice by continuous exposure to apomorphine. AB - Mice with unilateral lesions of the nigrostriatal dopaminergic neurons, induced by an intrastriatal injection of 6-hydroxydopamine, respond to an acute injection of apomorphine by rotating in a direction contralateral to the lesion. The dose of apomorphine that produced a half-maximal turning response was 0.4 mumol/kg s.c.; maximal turning responses were seen at 2 mumol/kg s.c. This behavioral supersensitivity may be due to an increased density of dopaminergic receptors. To determine whether continuous stimulation of these receptors with a dopaminergic agonist would reverse the dopaminergic behavioral supersensitivity, mice were exposed to continuous infusion of apomorphine via a s.c. implanted osmotic minipump containing 150 mumol of apomorphine in 0.2 ml and then challenged with an acute injection of apomorphine (2 mumol/kg s.c.) at varying times after the implant. Initially, the mice displayed spontaneous rotational behavior beginning by 1 hr after implantation, but this spontaneous behavior diminished over time and was absent by 4 days after implantation. The turning response of mice challenged with an acute injection of apomorphine was significantly reduced at 1 day after the chronic implantation and was totally absent at 2 and 4 days after implantation. This effect of continuous exposure to apomorphine was found to be concentration- and time-dependent; mice implanted with pumps containing 75 mumol of apomorphine required 8 days of exposure for tolerance to develop. Upon removal of the apomorphine-containing implants, the supersensitive rotational behavior returned over a 7-day period, with 50% recovery occurring at 2 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3088261 TI - Behavioral toxicity of chronic ethosuximide and sodium valproate treatment in the epileptic baboon, Papio papio. AB - The purpose of this study was to assess the effects of chronic administration of gradually increasing doses of the anti-petit mal agents, ethosuximide (15-60 mg/kg/day) and valproic acid (7.5-240 mg/kg/day) on the performance of incremental repeated acquisition and incremental fixed-ratio tasks in the epileptic baboon, Papio papio. At approximately equipotent anticonvulsant doses, ethosuximide (45-60 mg/kg/day) was more behaviorally toxic than valproic acid (7.5-60 mg/kg/day), as determined by the ability of each drug to suppress the incremental repeated acquisition of behavioral chains. The behavioral deficits induced by ethosuximide (60 mg/kg/day) were still present 8 weeks after cessation of drug treatment in two of four animals. Evidence of enhanced acquisition of behavioral chains (decreases in errors) was noted in two of six animals during chronic treatment with valproic acid at a dose of 60 mg/kg/day but was never seen during chronic treatment with ethosuximide. Responding under an incremental fixed ratio schedule of reinforcement was only affected minimally by either drug. These data suggest that 1) cognitive processes are more vulnerable to disruption by chronic ethosuximide administration than they are to chronic valproic acid administration, 2) performance under the more complex incremental repeated acquisition schedule is more sensitive to disruption than that under an incremental fixed-ratio schedule and 3) the effects of ethosuximide and valproic acid on performance under the incremental repeated acquisition schedule are not due to decreases in motivation or ability to manipulate the response levers. PMID- 3088262 TI - Eicosanoid synthesis by rabbit hydronephrotic cortical interstitial cells in culture. AB - Rabbit hydronephrotic cortical interstitial cells in primary culture were labeled with [1-14C]arachidonic acid and the eicosanoids released after stimulation with bradykinin or A23187 were studied by reverse-phase high performance liquid chromatography. The major arachidonic acid metabolite formed was prostaglandin (PG)E2, comprising more than 30% of the total radioactivity released. 12 Hydroxyheptadecatrienoic acid, probably representing spontaneous breakdown of the cyclic endoperoxides PGG2 and/or PGH2, made up 10 to 15% of the radioactivity released. Other cyclooxygenase products that were released included PGF2 alpha, PGD2, 6-keto PGF1 alpha and only minute amounts of thromboxane B2. Small quantities of the lipoxygenase products 15-, 12- and 5-hydroxyeicosatetraenoic acids (HETEs) as well as leukotrienes (LT)B4, LTC4 and LTD4 were also identified. Significantly larger quantities of 15- and 5-HETEs were recovered at 2 to 5 min than after longer incubations with A23187, suggesting esterification of these HETEs into cellular phospholipids. The data indicate that interstitial cells of the hydronephrotic kidney synthesize a variety of cyclooxygenase and lipoxygenase products of arachidonic acid, which may contribute to the pathophysiology of hydronephrosis. Moreover, it is suggested that PGG2 and/or PGH2 that are released from these cells may be metabolized further by adjacent kidney cells or circulating blood elements to other eicosanoid products, thus increasing the diversity of eicosanoids synthesized in the hydronephrotic kidney. PMID- 3088264 TI - The effects of arterial blood gas tensions on pressor responses to angiotensin II in the pithed rat. AB - The influence of arterial blood gas tensions on angiotensin II-mediated pressor responses in the pithed rat was studied by altering the inspired gas mixture at a fixed tidal volume. When rats were ventilated to produce physiological Pa, CO2 levels (35-40 mmHg) responses to boluses of angiotensin II were greater with increasing Pa, O2 over the Pa, O2 range of 65-460 mmHg. There was no difference in response to angiotensin II over the Pa, CO2 range studied (18-50 mmHg). All variations in response to angiotensin II were attributable to changes in Pa, O2. Since arterial blood gas tensions, especially the Pa, O2, modulate pressor responses to boluses of angiotensin II, the physiological effects of this hormone may be most fruitfully explored in rats ventilated to produce normal arterial blood gas tensions. PMID- 3088263 TI - Incorporation of calcium buffers into salamander retinal rods: a rejection of the calcium hypothesis of phototransduction. AB - The suction-electrode technique was used to monitor the photocurrent of isolated retinal rods from the tiger salamander, by drawing in the light-sensitive outer segment, or sometimes the inner segment. Calcium buffers or other agents were then introduced into the rod cytoplasm by the 'whole-cell patch-clamp' technique. A patch pipette was sealed against the region of the rod protruding from the suction pipette (usually the inner segment), and the membrane patch was ruptured to obtain a whole-cell recording. Several lines of evidence indicated that the pipette contents diffused into the outer segment, and showed that the cell could be adequately voltage clamped. With only trace quantities of chelator in the patch pipette (to bind stray calcium), a gradual decline of the dark current and slowing of responses was usually observed over a period of 10-20 min after rupture of the patch. When the patch pipette contained no added calcium and 10 mM of the calcium chelator BAPTA (1,2-bis(o-aminophenoxy)ethane-N,N,N',N' tetraacetic acid) (free Ca2+ ca. 10(-9) M) rupture of the patch led, over a period of a few minutes, to an increase in mean dark current, an increased duration of responses, a substantial increase in flash sensitivity, and a pronounced overshoot in the recovery phase, but with virtually no change in the rising phase of the response to bright flashes. Similar results were obtained when EGTA was used in place of BAPTA, and also in the few cases when successful rupture of the outer segment membrane was obtained. With the free calcium concentration in the patch pipette buffered to the higher level of 1 microM (with 10 mM-Ca2+/11 mM-BAPTA) the results were qualitatively similar to those obtained with BAPTA alone, except that the mean dark current did not increase. This is consistent with a resting free calcium concentration in darkness in the region of 1 microM. In the presence of bright steady illumination with BAPTA in the cell the suppression of outer segment current could be maintained for at least 15 min. Upon extinction of the light a very large current transient developed (similar to the overshoot with flashes) which was light suppressible. With backgrounds of moderate intensity the incorporation of buffer led to a gradual reduction of the residual current.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3088266 TI - Placebo controlled double-blind trial of fluvoxamine maleate in the obese. AB - Obesity and depression are common disorders which may co-exist. The management of the combination is complicated because some antidepressants cause weight gain fenfluramine, an effective antiobesity agent, may cause depression. Fluvoxamine is an antidepressant which, like fenfluramine, inhibits serotonin re-uptake within the brain. Forty obese female subjects with refractory obesity participated in a double-blind placebo controlled trial. During the twelve week study, those subjects receiving fluvoxamine achieved a mean weight loss greater than, but not significantly different from, that of the placebo group. The result suggests that fluvoxamine may be particularly useful in the management of obese patients requiring treatment with an antidepressant. PMID- 3088265 TI - Your CE topic this month (No. 16). An update on urinary tract infections. PMID- 3088267 TI - Cost-benefit analysis of psychosomatic therapy in asthma. AB - The effectiveness of psychosomatic therapy for asthma patients is difficult to prove. We tried to solve this problem in a new way by means of a cost-benefit analysis. To draw up such an analysis, we selected 22 patients capable of working out of a total of 57 patients with asthma bronchiale at the Heidelberg Medical Hospital, who were interested in participating for one year in a psychosomatic coping group therapy. These 22 patients were divided into two groups. The distribution of the relevant individual parameters in both groups was similar. We subjected the patients to three medical and psychodiagnostic examinations: one before treatment was started, a second after the first year of treatment and a third one and a half years later. Additional data were gathered from health insurance organisations and General Practitioners. Despite the bad prognoses of our patients, those treated, when compared to the untreated patients, had a significant reduction in the number of working days lost and a considerable decrease in the number of working days hospitalized. The savings resulting from these reductions were compared with the sum expended for group therapy; we found a cost-benefit ratio of 1:5. These results indicate that a cost-benefit analysis may be very helpful in evaluating the effectiveness of some psychosomatic treatment techniques. Moreover, coping group therapy completes the medical standard therapy of patients with bronchial asthma and is thus a means of reducing the high medical treatment costs of asthma patients. PMID- 3088268 TI - Timing of multiple ovulations in the ewe after treatment with FSH or PMSG with and without GnRH. AB - Ovulation rate, median time to first ovulation, median time of all ovulations and median time from first to last ovulation were studied by repeated laparoscopy in Merino ewes. Treatments with FSH or PMSG significantly affected ovulation rate (8.4 +/- 0.81 and 7.3 +/- 1.21 respectively, P less than 0.05) and in median time of all ovulations (60 and 54 h respectively after progestagen sponge removal, P less than 0.05). Differences in the median time to first ovulation (60 and 48 h) and median time from first to last ovulation (6 and 6 h) for the respective treatments were not significant. The synchrony of ovulation after both treatments was adversely affected by (1) the occurrence of premature ovulations before the onset of superovulation, (2) variability in the time of commencement of superovulation, and (3) variability in the time from first to last ovulation. Administration of GnRH synchronized the timing of ovulation with both gonadotrophin treatments. This synchrony was due to a reduction in the period during which superovulation began and in the interval from first to last ovulation. The median time of all ovulations was significantly less with FSH + GnRH than with PMSG + GnRH (45 and 48 h after progestagen sponge removal, respectively, P less than 0.05). Administration of GnRH at 16, 20 or 24 h after progestagen sponge removal significantly affected all traits examined except ovulation rate. Administration at 20 and 24 h produced an equally good synchrony of ovulation which was better than that obtained at 16 h. We suggest that the use of GnRH in embryo collection programmes appears justified and is likely to improve embryo yields due to improved rates of fertilization. PMID- 3088269 TI - Effects of danazol on spermatogenesis in adult rats. AB - Adult male Wistar rats were treated with Danazol (4 mg/day s.c.) for 52 days. The drug produced a marked, rapid drop in serum testosterone concentrations to very low levels and caused a slower decrease in serum FSH, LH and testis weight. Flow cytometric analysis of testicular cell suspensions showed a decline in the absolute numbers of haploid cells (spermatids), tetraploid cells (mainly pachytene spermatocytes) and of cells in the S-phase of the division cycle, suggesting that Danazol inhibited proliferation of spermatogonia and/or primary spermatocytes. Histological counting of the different types of spermatogonia, however, revealed no significant change in their numbers during Danazol treatment. It is concluded that Danazol inhibited spermatogenesis primarily after the preleptotene stage of primary spermatocytes. PMID- 3088270 TI - Postnatal ovarian follicle development in hypogonadal (hpg) and normal mice and associated changes in the hypothalamic-pituitary ovarian axis. AB - Significant uterine growth occurred in normal and hypogonadal (hpg) mice between Days 7 and 21 but thereafter no further growth was observed in hpg mice. The ovaries of hpg mice were significantly smaller than those of normals at all ages, but there was no significant difference between the number of non-growing follicles in the ovaries of mutants and their normal littermates at any age studied, and normal and hpg mice showed a marked reduction in the number of non growing follicles during the first month of life. The size and composition of the growing follicle population in hpg mice, however, differed markedly from those in normal animals and by 21 days of age the number of growing follicles in mutants was significantly reduced. There was no significant difference in the number of Type 3b follicles before 60 days of age, but the number of all other follicle types was significantly less in hpg mice at all ages studied. Follicles in which the antrum is fully developed (Type 7 and 8) were never seen in the ovaries of mutants and corpora lutea were never observed. Interstitial tissue development was also very poor in hpg ovaries. The hypothalamic GnRH content in normal mice remained low until Day 20, before rising sharply to adult levels (approximately 800 pg) between Days 20 and 30. The pituitary FSH content increased over the first 10 days of life to reach a peak of about 5000 ng, before declining to the adult value of about 2000 ng by Day 30, whilst the plasma FSH concentration was high in the first 10 days, but fell to adult levels over the next 20 days. Pituitary LH content increased significantly between Days 5 and 10 to reach the adult level of about 600 ng. Hypothalamic GnRH was undetectable at all ages in hypogonadal mice, but the pituitary content of FSH and LH had risen to the attenuated mutant adult value by Day 15, and unlike normals, plasma FSH concentrations were not elevated during the neonatal period. These results suggest that minimal gonadotrophic stimulation of the ovary from birth has no effect on the total number of follicles but reduces the number of growing follicles and prevents follicle growth beyond the early antral stage. Gonadotrophins therefore appear to have a role in the initiation and continuance of follicle growth in the adult mouse. PMID- 3088271 TI - Effects of oral contraceptives on cholesterol. AB - Studies have shown that the effects of progestins on lipid metabolism seem to be related to dose, not to the specific agent. PMID- 3088272 TI - Oral contraception, 1986. Currently available formulations. AB - Although approximately 49 oral contraceptive products are available in the U.S., most have similar pharmacologic action. Only compounds containing norgestrel are metabolized by a different route. PMID- 3088273 TI - Peripheral blood T lymphocyte subsets in active rheumatoid arthritis--effects of different therapies on previously untreated patients. AB - Peripheral blood T lymphocyte subset levels were prospectively analyzed in previously untreated patients with active rheumatoid arthritis (RA) with different drug regimens. Before treatment the patient group had reduced numbers of Leu 2a+ lymphocytes compared with controls (p less than 0.001). During penicillamine and chloroquine treatment a marked reduction in absolute numbers of Leu 3a+ lymphocytes was seen (p less than 0.01), whereas treatment with nonsteroidal antiinflammatory drugs was characterized by increased absolute numbers of Leu 2a+ lymphocytes (p less than 0.02). Thus, there seems to be a predictable variation of T lymphocyte subsets in RA with certain drug regimens. PMID- 3088274 TI - Molecular characterization of Ro(SSA) and La(SSB) proteins. AB - Ro(SSA) and La(SSB) proteins were characterized using human spleen extract as antigen and monospecific anti-Ro(SSA) and anti-La(SSB) sera. The antigens were partially purified by DEAE cellulose and Sephacryl chromatography, and then were electrotransferred to nitrocellulose sheets after SDS-PAGE electrophoresis. The anti-Ro(SSA) sera had reacted with a polypeptidic band of 58 kilodaltons (kDa), meanwhile the La(SSB) antisera reacted with 2 polypeptidic bands of 42 and 40 kDa. The molecular weight of the Ro(SSA) and La(SSB) proteins obtained by gel filtration chromatography was in agreement with the PAGE/electrotransfer results. These procedures are useful tools for the molecular analysis of the markers in the connective tissue diseases. PMID- 3088275 TI - The use of lidocaine to reduce the pain of myochrysine injections for children with juvenile rheumatoid arthritis. AB - Myochrysine (gold sodium thiomalate, GSTM) injections are the therapy of choice for children with refractory juvenile rheumatoid arthritis. In this single blinded study 8 children receiving GSTM were asked to rate their discomfort after a total of 185 injections of GSTM to which were added in random fashion either 0, 0.1, or 0.25 ml of 1% lidocaine. The addition of 0.1 ml of lidocaine was associated with a reduction of the mean complaint of pain on an ordinal pain score of 1-10 from 4.32 for injections containing no lidocaine to 2.54 for injections containing 0.1 ml (p less than .01). Addition of 0.25 ml of lidocaine did not provide a significant increase in pain reduction (p greater than .05). PMID- 3088276 TI - Pulmonary hypertension in systemic lupus erythematosus: a report of three cases. AB - Three women with systemic lupus erythematosus (SLE) who developed pulmonary hypertension as a terminal feature of their illness, are reported. One patient with quiescent SLE had marked sicca syndrome when pulmonary hypertension developed. Two of the 3 patients possessed the "lupus anticoagulant" and antibodies to cardiolipin. All 3 patients had positive rheumatoid factor in their sera. PMID- 3088277 TI - Hypogammaglobulinemia and lung infiltrates after gold therapy. PMID- 3088278 TI - Walker-Warburg syndrome (Warburg syndrome, HARD +/- E syndrome). PMID- 3088280 TI - Transfer of a chromosomal locus responsible for mucoid colony morphology in Pseudomonas aeruginosa isolated from cystic fibrosis patients to P. aeruginosa PAO. AB - The locus responsible for mucoid colony morphology in five independent clinical isolates of Pseudomonas aeruginosa from cystic fibrosis patients have been transferred by means of pM060-mediated conjugation to the genetically characterised strain P. aeruginosa PAO. Genetic mapping has shown that in all five strains the locus is on the chromosome between 89' and 94', although it is not possible to say that the same locus is involved in each case. The way is now open for a more detailed genetic analysis of the loci responsible for mucoid colony morphology. PMID- 3088279 TI - Growth of Clostridium difficile and production of toxins A and B in complex and defined media. AB - The ability of several strains of Clostridium difficile to grow and to produce toxins A and B in complex and defined culture media has been studied with special reference to the amino-acid composition of the medium. The production of these toxins varied with the strain used and with the composition of the growth medium. Toxin A production was not inextricably linked to production of toxin B since conditions were found in which only one or other toxin was produced. PMID- 3088281 TI - A modified scheme for biotyping Gardnerella vaginalis. AB - A scheme is proposed for biotyping Gardnerella vaginalis, based on detection of hippurate hydrolysis, beta-galactosidase (ONPG) and lipase, and fermentation of arabinose, galactose and xylose. Seventeen biotypes were found among 197 strains from asymptomatic women and patients with bacterial vaginosis (non-specific vaginitis). The distribution of biotypes was similar in both populations but some biotypes were found more frequently in patients. The proposed scheme is compared with those previously described. PMID- 3088282 TI - An immobilized fork as a termination of replication intermediate in Bacillus subtilis. AB - The structure of a DNA intermediate associated with termination of chromosome replication in Bacillus subtilis and derived from a unique BamHI 24.8 X 10(3) base-pair (bp) region of the chromosome has been investigated. The intermediate has properties expected for a forked structure. Gel electrophoresis followed by Southern transfer and hybridization to cloned DNA has shown it to comprise single strands of 15.4 X 10(3) bp and 24.8 X 10(3) bp, in approximately equimolar amounts. After purification away from the bulk of chromosomal DNA, electron microscopy of the intermediate established that 15% of the DNA was present as branched molecules and a significant proportion (11 of 31) of these contained two arms of matching length. The average dimensions (best estimates) of this unique class of Y-shaped molecule were 9.5(+/- 0.3) X 10(3), 15.1(+/- 0.4) X 10(3) and 24.6 24.6(+/- 0.6) X 10(3) bp for the stem, arms and end-to-end length, respectively. These values are consistent with the single strand composition of the intermediate as found. Furthermore, hybridization of the single strands to DNA from known locations within the BamHI 24.8 X 10(3) bp region has established the orientation of the forked intermediate relative to the genetic map. The intermediate presumably reflects the immobilization of the clockwise replication fork within the 24.8 X 10(3) bp region, at a location approximately 15.4 X 10(3) bp from the right end. PMID- 3088283 TI - Structure and composition of ferritin cores isolated from human spleen, limpet (Patella vulgata) hemolymph and bacterial (Pseudomonas aeruginosa) cells. AB - Ferritin cores isolated from human spleen, limpet (Patella vulgata) hemolymph and bacterial (Pseudomonas aeruginosa) cells have been investigated by high resolution transmission electron microscopy, electron diffraction and chemical analysis. Hemosiderin particles isolated from thalassemic spleens also have been studied. The results show that there is a marked difference in structure and composition of the biomineral phases. Human ferritin and hemosiderin particles are single domain crystals of hydrated iron (III) oxide (ferrihydrite). Lattice fringes were low in contrast and often discontinuous within the central regions of the core. Heat treatment of human ferritins results in a 5 A shrinkage in particle size and an increase in the single crystalline nature of the core. In contrast, lattice images and electron diffraction of limpet and bacterial cores show no evidence of long-range crystallographic order. Chemical analysis indicates a high inorganic phosphate (Pi) (Fe/Pi = 1.71) content in bacterial ferritin compared with human ferritin (thalassemic) (Fe/Pi = 21.0). The high Pi content of bacterial ferritin suggests a hydrated amorphous iron (III) phosphate mineral core. Structural disorder within the limpet and bacterial cores may be associated with increased Pi content and increased oxidation in Fe(II), resulting in rapid mineral deposition. Growth of the iron (III) oxide cores in human ferritin is discussed on the basis of high resolution electron microscopy results. PMID- 3088284 TI - Identification of protein sequence homology by consensus template alignment. AB - A pattern-matching procedure is described, based on fitting templates to the sequence, which allows general structural constraints to be imposed on the patterns identified. The templates correspond to structurally conserved regions of the sequence and were initially derived from a small number of related sequences whose tertiary structures are known. The templates were then made more representative by aligning other sequences of unknown structure. Two alignments were built up containing 100 immunoglobulin variable domain sequences and 85 constant domain sequences, respectively. From each of these extended alignments, templates were generated to represent features conserved in all the sequences. These consisted mainly of patterns of hydrophobicity associated with beta structure. For structurally conserved beta-strands with no conserved features, templates based on general secondary structure prediction principles were used to identify their possible locations. The specificity of the templates was demonstrated by their ability to identify the conserved features in known immunoglobulin and immunoglobulin-related sequences but not in other non immunoglobulin sequences. PMID- 3088285 TI - Fine structure of the photosensitive iris of the toad, Bufo marinus. AB - The iris of the toad Bufo marinus is directly photosensitive and will constrict in response to light striking only the iris. This is true even when the iris is isolated from the rest of the eye, and therefore from reflex neuronal influences initiated in the retina. This autonomous response is probably mediated by the sphincter pupillae muscle, since no specialized photoreceptors are present in the iris, nor does the sphincter exhibit any specializations likely to subserve a purely photoreceptive function. The photosensitive sphincter appears typical of smooth muscle and, like mammalian sphincters, possesses many intercellular junctions. The iris possesses a well-developed neuronal plexus with fibers projecting into the sphincter muscle layer. Nerve terminals contain small, agranular (30-70nm) and large, dense-cored (80-120nm) vesicles. No consistent postsynaptic specializations are seen on any cells of the iris, including the cells of the sphincter muscle. The anterior pigment epithelial cells of the iris appear specialized and resemble the myoepithelial dilator muscle described by Kelly and Arnold ('72) for the iris of rats. PMID- 3088286 TI - Delayed phosphorylation of the largest neurofilament protein in rat optic nerve development. AB - Monoclonal antibodies selectively reacting with the high molecular weight neurofilament proteins (NF 150K and NF 200K) on immunoblots of bovine spinal cord extracts were obtained upon immunization of mice with chicken brain antigen and with highly purified NF 150K or NF 200K isolated from bovine spinal cord by anion exchange chromatography. Antibodies reacting with NF 200K or with both NF 150K and NF 200K were selected for this study. The antibodies were screened on immunoblots for reactivity with phosphorylated epitopes by dilution of the supernatants in sodium potassium phosphate as well as by treatment of nitrocellulose transfers with alkaline phosphatase. Abolishment of staining under these conditions was taken as evidence of reactivity with phosphorylated epitopes. With phosphate/phosphatase-sensitive antibodies, NF 200K immunoreactivity was a late event in rat optic nerve development. It was first observed at day 18 on immunoblots of sodium dodecyl sulfate extracts analyzed by gel electrophoresis. Conversely, with phosphate/phosphatase-insensitive antibodies, NF 200K immunoreactivity was already present on day 10, the earliest age in this study. With one monoclonal reacting with phosphorylated NF 150K and NF 200K, NF 150K immunoreactivity was already present on day 10. It is proposed that NF 200K expression precedes NF 200K phosphorylation in development. PMID- 3088287 TI - Comparison of the effect of three adrenal corticosteroids on human granulocyte function against Pseudomonas aeruginosa. AB - The effect of hydrocortisone, methylprednisolone, and dexamethasone on the phagocytic and bactericidal capabilities of normal human granulocytes (PMN) was studied under previously described optimal conditions for Pseudomonas aeruginosa, PA 1348A. At hydrocortisone and methylprednisolone concentrations of 1,000 micrograms/ml, delayed phagocytosis was clearly observed, whereas dexamethasone 400 micrograms/ml had no effect on phagocytosis. The bactericidal effect of PMN on PA 1348A was significantly reduced by all three corticosteroids at highest concentrations (p less than 0.05). However, the effect of methylprednisolone was greatest and that of dexamethasone was least evident, 25% and 10% reduction in PMN bactericidal activity, respectively. Following exposure to the highest concentrations of corticosteroids, TEM observations correlated well with the PMN functional assays. While the observations of PMN and bacteria in controls, hydrocortisone, and dexamethasone preparations were similar, evidence for incomplete phagocytosis, lack of vacuole coalescence, minimal disruption of bacterial cell walls, and dividing bacteria in phagosomes were evident in methylprednisolone preparations. These PMN functional and TEM observations suggest that of the three corticosteroids studied, methylprednisolone appears most deleterious to the PMN phagocytic and bactericidal activity. PMID- 3088288 TI - Effect of ingesta on systemic availability of penicillins administered orally in dogs. AB - Six penicillin preparations were administered to six dogs of various types, both when the dogs were fasted and when fed a standard meal immediately before dosing. The preparations used were: amoxycillin tablets and drops, ampicillin tablets, penicillin V tablets, phenethicillin tablets and cloxacillin capsules. A Latin square design was employed with ampicillin and the two amoxycillin preparations, while three separate cross-over studies were done with penicillin V, phenethicillin and cloxacillin. Dose rates used were 50 mg/kg for cloxacillin, and 10 mg/kg for the others. A microbiological method was used to assay penicillin in blood samples taken at intervals after dosing. Values for peak plasma drug concentration (Cmax), the time at which it occurred (Tmax), and area under the curve (AUC) were obtained for each curve of drug concentration plotted against time. In fasted dogs, ampicillin showed poorer systemic availability than did amoxycillin, with Cmax and AUC values of less than half those of amoxycillin. The solid and liquid preparations of amoxycillin had similar bioavailability. Ingesta adversely affected the systemic availability of antibiotic from all preparations tested. With ampicillin and both amoxycillin preparations, there were reduced Cmax and AUC and prolonged Tmax, indicating slowed and diminished absorption. Feeding did not alter Tmax with the other drugs, but reduced the Cmax of penicillin V, phenethicillin and cloxacillin and the AUC of cloxacillin. It is suggested that, if minimal impairment of bioavailability by ingesta is desired, then the penicillins commonly administered by mouth (amoxycillin, ampicillin, penicillin V, phenethicillin, cloxacillin) should be given to dogs that are fasting. PMID- 3088289 TI - Effect of heparin and EDTA anticoagulants on phenylbutazone levels in equine plasma. PMID- 3088290 TI - Mycobacterium tuberculosis bacteremia in the acquired immunodeficiency syndrome. PMID- 3088291 TI - Aplastic crisis or erythroid hypoplasia in sickle cell disease? PMID- 3088292 TI - Lupus anticoagulant in the acquired immunodeficiency syndrome. AB - Prolongation of partial thromboplastin time was noted in patients with acquired immunodeficiency syndrome (AIDS) who were admitted to the hospital for diagnosis of opportunistic infection. As biopsy procedures were often indicated, detailed investigation of the abnormal coagulation study was performed in four patients. Results confirmed the presence of a lupus anticoagulant. Partial thromboplastin times of 34 consecutive subsequent patients hospitalized with the diagnosis of AIDS-associated opportunistic infection were recorded; prolongation was noted in 24 of these. None of these 38 patients exhibited clinical evidence of bleeding. One patient had a confirmed thrombotic episode. Prolonged partial thromboplastin time is a common finding in hospitalized patients with AIDS and opportunistic infection. If no clinical history of unusual bleeding is noted, the lupus anticoagulant should be suspected. Many patients with AIDS require invasive procedures for disease management; the lupus anticoagulant, an in vitro phenomenon, should not prevent these studies. PMID- 3088293 TI - Leads from the MMWR. Non-A, non-B hepatitis associated with a factor IX complex infused during cardiovascular surgery--Arizona. PMID- 3088294 TI - Heterosexual transmission of AIDS. PMID- 3088295 TI - Costs and benefits of medical student training to a health maintenance organization. AB - As health maintenance organizations (HMOs) and managed health care systems expand, they represent an increasing potential as sites for medical student teaching. Considerable difference of opinion exists about the impact of medical training on these prepaid delivery systems. This study presents a methodology for estimating the subjective and objective costs and benefits of medical student training to an independent staff model HMO with a long-standing training program. Data are derived from a provider survey, a consumer survey, and patient visit logs. Principal subjective benefits include increased perceived quality of care, improved patient satisfaction, and enhanced provider education and joy of practice. Objective impacts include a decrease in productivity of 1.1 patient visits per half day and direct physician teaching labor of 46.8 minutes per half day. Applying this methodology to the specific program of ten courses gives rise to a figure of $180 000 ($16 900 per full-time equivalent student per year) for the "opportunity cost" of medical student training to the HMO. Rules of thumb are developed for application of this method prospectively to new programs in similar relationships between staff model HMOs and academic medical centers. PMID- 3088296 TI - Compliance of human pulmonary "venous" system estimated from pulmonary artery wedge pressure tracings--comparison with pulmonary arterial compliance. AB - To evaluate the reservoir function of the pulmonary vascular bed for the left ventricle, the compliance of the pulmonary "venous" system (Cp'v') (consisting of the pulmonary veins and the left atrium) and that of the pulmonary arterial system (Cpa) were sequentially estimated in each of 31 subjects by using Hirakawa's and Engelberg's methods, respectively. In control cases (n = 6), Cpa was 6.68 +/- 3.52 (mean +/- SD) ml/mmHg and Cp'v' was 15.81 +/- 6.85 ml/mmHg. In patients with mitral stenosis (MS) of Class I (previous classification of NYHA) (n = 7), Cpa was 4.05 +/- 2.71 ml/mmHg and Cp'v' was 13.15 +/- 4.51 ml/mmHg. In patients with MS of Class II (n = 13), Cpa was 2.81 +/- 1.05 ml/mmHg and Cp'v' was 8.40 +/- 2.95 ml/mmHg. In MS of Class III (n = 5), Cpa was 1.54 +/- 0.80 ml/mmHg and Cp'v' was 7.10 +/- 1.91 ml/mmHg. These results indicate that both systems become less compliant as the cardiac functional capacity deteriorates. The ratio of Cp'v' to Cpa (Cp'v'/Cpa) was 2.7 +/- 1.1 in control cases, 3.9 +/- 1.4 in MS of Class I, 3.4 +/- 1.6 in MS of Class II and 5.3 +/- 2.1 in MS of Class III. When one compares these results with the compliance in the systemic circulation, i.e., 118 ml/mmHg in the veins and 2.5 ml/mmHg in the arteries, giving the ratio of 118/2.5 not equal to 50, it is obvious that the compliance of the pulmonary arterial system shares a sizable portion of the total compliance in the pulmonary vascular bed. The relationship between Cp'v' and the internal pressure, namely the mean pulmonary artery wedge (PAW) pressure, was expressed with a regression equation of, Cp'v' = 1/(0.003 PAW + 0.080), indicating that Cp'v' is inversely related to the internal pressure. In 12 of patients with MS, sublingual nitroglycerin shifted the Cp'v'-PAW pressure plots upwards and to the left, roughly along the Cp'v'-PAW regression curve for the entire groups of MS. PMID- 3088298 TI - [A randomized controlled trial of immunochemotherapy using carmofur (HCFU), mitomycin C and immunopotentiators in advanced gastric cancer following noncurative resection and nonresection]. AB - The cumulative survival rate of 166 gastric cancer patients after noncurative resection and nonresection treated by combination therapy using carmofur (HCFU), mitomycin C (MMC) and immunopotentiators was investigated. A randomized controlled trial composed of MMC and immunopotentiators (group A) versus the addition of HCFU to group A (group B) was undertaken. In all patients, the survival curve of group B was superior to that of group A (g. Wilcoxon test, p = 0.078). Noncurative resection or nonresection patients presented significantly higher survival rates in group B (p less than 0.05) after analysis according to the duration of the treatment period (Z-test). Stratification of backgrounds for noncurative patients also showed significantly higher survival rates in group B (p less than 0.05) at S 3, P, stage IV. From these results, it might be suggested that HCFU therapy is useful for gastric cancer patients after noncurative resection and nonresection. PMID- 3088297 TI - Sinus node function after selective elimination of sympathetic influences on the sinus node area of the dog. AB - Six-hydroxydopamine (6OHDA) was injected directly into the subepicardium of the sinus node area in an attempt to damage sympathetic nerve terminals in the sinus node. The changes in sinus node function were observed for 4 weeks. The predominant rhythm was of sinus origin throughout the observation period. The sinus rate progressively decreased from 145.1 +/- 14.2 to 76.2 +/- 12.1 beats/min during the first week after injection of 6OHDA. The sinus rate remained at this level for 2 weeks, followed by a gradual increase to 89.3 +/- 18.2 beats/min 4 weeks after injection of 6OHDA. These sinus rates were only significantly different from control dogs through the 14th postoperative day. The sinus rate was considerably increased by intravenous atropine injections 5 to 7 days after the injection of 6OHDA into the sinus node area. The sinus node recovery time was much longer in dogs with an injection of 6OHDA than that in the control dogs throughout the observed period. These results suggest that elimination of the sympathetic influences on the sinus node can be achieved by direct injection of 6OHDA into the sinus node area in the dog, and that sinus node function can be depressed by decreasing sympathetic tone alone, in the absence of an intrinsic dysfunction of the sinus node. PMID- 3088299 TI - [An unusual case showing a conversion of clinicopathologic features from B chronic lymphocytic leukemia to primary macroglobulinemia]. PMID- 3088300 TI - [Hodgkin's disease associated with pure red cell aplasia--report of a case]. PMID- 3088301 TI - [Indications and clinical aspects of intraoperative radiation therapy]. PMID- 3088302 TI - Abnormalities of cerebral lipids in GM1-gangliosidoses, infantile, juvenile, and chronic type. AB - Cerebral lipids of patients with GM1-gangliosidoses, infantile, juvenile, and chronic type which are caused by deficiency of beta-galactosidase, were examined and compared to each other. The infantile type demonstrated abnormal accumulation of GM1 and asialo-GM1 in contrast with marked decrease in such major cerebral lipids as cholesterol, phospholipids, cerebroside, and sulfatide. It was also noted that significant amounts of such unusual lipids as free fatty acids, GlcCer, LacCer, GbOse3Cer, and GbOse-4Cer plus nLcOse4Cer were found in the brain. These findings pointed out that this infantile type might accompany a severe cerebral dysgenesis with poor myelination. The juvenile type also showed marked increase in GM1 and asialo-GM1, but the decrease in cholesterol, phospholipids, cerebroside, and sulfatide was not so much as the infantile type. These findings along with the occurrence of cholesterol ester suggested that the brain caused progressive demyelination after the immature myelin appeared. An autopsized brain tissue of a male patient who was eventually diagnosed as a case of GM1-gangliosidosis chronic type after his death, showed some accumulation of GM1 and asialo-GM1 particularly in the caudate nucleus and putamen, whereas it showed moderate amounts of GM1 in apparently normal gray and white matters. It seemed that there are no abnormal cerebral lipids except for gangliosides and some neutral glycosphingolipids in the chronic type. PMID- 3088303 TI - The killing effect of subclasses of mouse IgG antibodies on schistosomula of Schistosoma japonicum. AB - The killing effect of IgG antibodies in sera from S. japonicum infected mice on schistosomula of S. japonicum was studied in vitro in the presence of complement. Immune mouse sera were fractionated over Protein A-Sepharose and IgG1, IgG2a, IgG2b and IgG3 were purified by affinity chromatography. The killing activity of each subclass of IgG antibodies against schistosomula was observed only in the presence of complement. The activity of IgG1 was higher than that of the other subclasses of IgG. In combination of the two or three subclasses of IgG, the additive mortality rate was given in all combinations of each subclass of IgG. These results support the view that the combination of various subclasses of IgG antibodies potentiates the resultant lethal effect on schistosomula. PMID- 3088304 TI - Electron microscopic observations of Descemet's membrane of peripheral cornea. AB - The posterior portion of the Descemet's membrane was studied by scanning and transmission electron microscopy; the materials comprised 87 human peripheral corneas with ages from 2 to 98 years, 5 monkey corneas and 4 rabbit corneas. In some specimens, the endothelium was removed by ultrasonication. After removal of the endothelium, "curly structures" were recognized on the surface of the Descemet's membrane, where the membrane showed a gradual thinning. These structures appeared along the whole circumference of the cornea with variable width in the human specimens, but in monkey and rabbit corneas, the extent of these structures was less than in the human cornea. The "curly structures" were not encountered in young subjects, and they increased with age. There was a positive correlation (r = 0.60, P less than 0.001) between the age and the extent of these structures. Other aging products of the Descemet's membrane, ie, Hassall Henle bodies, were partly surrounded by the "curly structures". The human "curly structures" consisted of collagen fibrils, halo structures in the collagen bundles, wide-spacing fibers, microfibrils, ground substances containing minute filaments and a structure resembling the Descemet's membrane. Components of "curly structures" of the monkey and rabbit were almost the same as those of the human except for the Descemet's membrane-like structure. PMID- 3088305 TI - Presence of tyrosinase activity in human ciliary body. AB - We examined tyrosinase activity in pigmented tissues from five human eyes. Tissue extract was prepared in cholate-phosphate buffer by homogenization, centrifugation, trypsin digestion and hydroxylapatite column chromatography. Tyrosinase activity was spectrophotometrically assayed as dopa (L-3,4 dihydroxylphenylalanine) oxidase activity. Tyrosinase activity was detected in the extracts of the ciliary body. Enzyme activity was inhibited by phenylthiourea but not by 3-iodo-tyrosine. We believe that our findings confirm the presence of tyrosinase activity in the human ciliary body. PMID- 3088306 TI - Purification of antibody against peanut agglutinin-receptors of bovine interphotoreceptor matrix. AB - From rabbit antiserum against peanut agglutinin (PNA)-receptors of the bovine interphotoreceptor matrix, an antibody was isolated by immunoaffinity chromatography on immobilized PNA-receptors. The antibody reacted with the bovine interphotoreceptor matrix at the molecular weight of 130,000 daltons. Immunohistochemical studies revealed that the antibody was bound not only to the surfaces of the cone photoreceptor cells but also to the surfaces of the rods, suggesting that the antibody purified here may have been formed by the major structure of glycoprotein that is common in the interphotoreceptor matrix around the cones and rods. PMID- 3088307 TI - Hypercapnic and hypoxic ventilatory responses during growth. AB - Cross-sectional studies on hypercapnic and hypoxic ventilatory chemosensitivities were performed in 71 children ranging in age from 7 to 18 yrs. The subjects were classified into 6 successive 2-year age groups. CO2 ventilatory response was measured by rebreathing 5% CO2 in O2, a slight modification of the method originally proposed by Read. The results were evaluated when the CO2-ventilation feedback control system was supposed to have attained the open-loop condition. Hypoxic ventilatory response was measured by the isocapnic progressive hypoxia test. To obtain good reproducibility in the ventilatory response, end-tidal PCO2 was maintained at 5 mmHg higher than the resting condition throughout the test. Normalized ventilatory responses to CO2 by body surface area (S/BSA) progressively decreased from the 7-8 through the 11-12 yr groups, and then tended to decrease further in a more gradual manner with increasing age. This trend was very similar to the normalized CO2 output (VCO2/BSA), but did not parallel so closely the normalized O2 intake (VO2/BSA). When ventilatory and metabolic parameters were normalized by body weight (BW), or the lean body mass (LBM), qualitatively similar relationships between CO2 sensitivities and metabolic parameters were also obtained. Contrary to the hypercapnic response, hypoxic ventilatory chemosensitivities were not significantly different among the 6 different age groups. We concluded that normalized hypercapnic chemosensitivity decreased during growth and corresponded well with decreased CO2 output per unit body mass. PMID- 3088308 TI - Numerical solution of partial differential equations describing the simultaneous O2 and CO2 diffusions in the red blood cell. AB - To describe the overall gas exchange rates in red blood cells (RBC), a computer program for solving the diffusion equations for O2, CO2, and HCO3-that accompany the chemical reactions of Bohr- and Haldane-effects was developed. Three diffusion equations were solved alternatively and repeatedly in an increment time of 2 ms. After solving the diffusion equations the Po2, O2 saturation (So2), Pco2, pH, and HCO3-content were corrected by using the Henderson-Hasselbalch equation, where the buffer value was newly derived from the CO2 dissociation curve. In computing the Haldane effect, the buffer value was taken to be 44mmol X l(RBC)-1 X pHc-1, so that the change in intracellular dissolved CO2 caused by the So2 change was fully compensated by the subsequent CO2 diffusion. The oxygenation and deoxygenation rate factors of hemoglobin were assumed to be 2.09 X (1-S)2.02 and 0.3s-1 X Torr-1, respectively. The Po2 change due to the Bohr-shift was computed from Hill's equation, in which the K value was given by a function of the intracellular pH. When the parameter values thus far measured were used, the computed Bohr- and Haldane-effects coincided well with the experimental data, supporting the validity of the equations. The overall gas exchange profiles calculated in the pulmonary capillary model showed that the CO2 equilibration time was significantly longer than the oxygenation time. PMID- 3088309 TI - Serum fatty acid concentrations in patients on postoperative parenteral nutrition with and without fat. AB - To examine changes in fatty acid composition of serum lipids, sixteen patients with gastric cancer were maintained on total parenteral nutrition (TPN) or intravenous feeding immediately after total gastrectomy. Subjects receiving no fat showed decreases in linoleic acid, linolenic acid and arachidonic acid and increases in palmitoleic acid and oleic acid, whereas those receiving fat emulsion showed no detectable changes. Decrease in the linoleic acid content was greater in subjects on a higher carbohydrate intake, but less in those on a higher fat intake. Multiple regression analysis of the relationships among carbohydrate intake (X1) and fat intake (X2) and changes in the linoleic acid percentage of total serum fatty acids (Y) in each case yielded an equation: Y = 4.75 X1 + 69.0 X2 - 27.9 (R = 0.885, p less than 0.05). Approximately 1 g/kg/day of fat provided in 40-50 kcal/kg/day of nonprotein energy intake was estimated to prevent decrease in the linoleic acid content in the serum fatty acid pattern during the postoperative catabolic stage. PMID- 3088310 TI - Variants of a human monocytic leukemia cell line (THP-1): induction of differentiation by retinoic acid, interferon-gamma, and T-lymphocyte-derived differentiation-inducing activity. AB - Induction of terminal differentiation of two variant sublines derived from the human monocytic leukemia cell line THP-1 by all-trans-beta-retinoic acid (RA) was studied. One of the variants was approximately 10 times more resistant to RA and the other, approximately 10 times more sensitive than the parent THP-1. Differentiation of the RA-resistant variant could be induced by immune interferon (IFN-gamma) and a T-lymphocyte-derived lymphokine of a differentiation-inducing activity (DIA), alone or in combination with 10 nM RA. These induced cells showed many of functional monocyte and/or macrophage characteristics, such as superoxide anion production, phagocytosis, and antibody-dependent cellular cytotoxicity. RA suppressed the expression of Fc receptors, phagocytosis, and 5'-nucleotidase activity of the resistant cells, although not the expression of the sensitive variant. These results indicate that RA-resistant cells can be fully induced to differentiate by the combination of RA and IFN-gamma or DIA. PMID- 3088311 TI - Lipid metabolism and enzyme activities in hormone-dependent and hormone independent mammary adenocarcinoma in GR mice. AB - Lipid metabolism in hormone-dependent (HD) GR mouse mammary tumors was compared to that in hormone-independent (HI) tumors and normal mammary tissues. HD tumors, like normal mammary tissue but unlike HI tumors, synthesized medium-chain-length fatty acids (MCFA). However, when treated with hormones (estrone and progesterone), the HI tumors were induced to produce MCFA. The activity of thioesterase II correlated positively with the synthesis of MCFA and was influenced by the hormones administered. The activities of NADP+-linked malate dehydrogenase, citrate lyase, acetyl-CoA carboxylase, and fatty acid synthetase, although lower in tumors than in normal glands, were not different in HD as compared to HI tumors. Whereas the predominating lipids synthesized in normal glands were triglycerides, phospholipids comprised about half of the lipid synthesized in the tumors, with no difference between HD and HI tumors. The conversion of D-[U-14C]glucose to 14CO2 was higher in HD tumors than in HI tumors but increased in HI tumors treated with hormones in vivo. By a comparison of the 14CO2 produced from D-[1-14C]glucose and from D-[6-14C]glucose in the presence and absence of an electron acceptor (methylene blue), it was demonstrated that regeneration of NADP+ from NADPH was a rate-limiting step for the pentose phosphate pathway in the tumors. Hence, while differences in the lipid metabolism can be demonstrated between HD and HI GR mouse mammary tumors, some of the changes are due to the hormone treatment rather than to a specific alteration in the tumor itself. PMID- 3088312 TI - Interaction of vitamin C and selenium supplementation in the modification of mammary carcinogenesis in rats. AB - The objectives of this study were a) to compare the efficacy of inorganic and organic selenium compounds in protecting against mammary tumorigenesis induced by 7,12-dimethylbenz[a]anthracene [(DMBA); CAS: 57-97-6] in rats and b) to study the interaction of vitamin C with either selenite (inorganic) or seleno-DL-methionine (organic) in chemoprevention. Control Sprague-Dawley rats were fed a purified 5% corn oil diet containing 0.1 ppm selenium. Selenite or seleno-DL-methionine was added to the basal diet in concentrations of 2, 3, or 4 ppm starting 1 week after DMBA administration. The inhibitory response in mammary tumorigenesis with selenium supplementation was dose dependent. Both selenium compounds were found to be equally efficacious in prophylaxis, although at the 4-ppm level a slight reduction in growth was observed. In the second experiment, different concentrations of vitamin C (0.2, 0.5, and 1%) were tested. In general, there was no change with the two lower levels; but a slight, although insignificant, increase in tumor yield was detected in rats supplemented with 1% vitamin C in the diet. The interaction of 0.5% vitamin C with either selenite or seleno-DL methionine (3 ppm) was studied in the third experiment. Results showed that the protective effect of selenite in tumorigenesis was nullified by vitamin C, whereas the chemopreventive action of seleno-DL-methionine was not affected. It is possible that selenite is reduced by vitamin C to elemental selenium and is therefore not available for uptake by tissues. This hypothesis was indirectly supported by tissue selenium measurements showing that 0.5 or 0.25% of vitamin C in the diet completely negated in blood, liver, and mammary gland the accumulation of selenium induced by 3 ppm of selenite supplementation. Lower levels of vitamin C (less than or equal to 0.1%) were found to have no effect on tissue selenium concentrations. Furthermore, the presence of 0.1% vitamin C in the diet no longer abolished the anticarcinogenic effect of selenite. This study suggests that high levels of vitamin C can interfere with the accumulation of tissue selenium and that an increased titer of this trace element in cells is essential for retarding tumor development. PMID- 3088313 TI - Antibodies to laminin in preeclampsia. AB - Laminin is a large basement membrane glycoprotein localized in the trophoblast, glomerular basement membrane and in the mesangial matrix of human glomeruli. It promotes the attachment of epithelial cells to basement membrane collagen. We have found that 14 sera from 52 patients with severe preeclampsia or eclampsia contain IgG and IgM antibodies which react with placental and kidney basement membranes. These antibodies were specific for laminin and did not react with other basement membrane proteins. They were able to fix complement. They have been demonstrated by radial immunodiffusion, radioimmunoassay and immunofluorescence blocking studies. In primary cultures they were shown to impair the attachment of trophoblast cells to basement membrane collagen. High levels of circulating immune complexes were detected only in sera from preeclamptic patients with circulating antibodies to laminin. The auto-antibodies to laminin could play a major role in the pathogenesis of severe preeclampsia by impairing the attachment of trophoblast cells to placental basement membranes and by fixation to the glomerular basement membranes and mesangial matrix. PMID- 3088315 TI - [Experimental studies of the usefulness of polydioxanone (PDS) threads for cerclage of the eyeball. 1. Clinical observations]. PMID- 3088314 TI - [CNS involvement in mycoplasma infections]. PMID- 3088316 TI - [Experimental studies of the usefulness of polydioxanone (PDS) threads for cerclage of the eyeball. 2. Macroscopic and histological evaluation]. PMID- 3088317 TI - [Use of absorbable polydioxanone (PDS) threads for cerclage of the eyeball]. PMID- 3088318 TI - [Immanuel Kant's disease]. PMID- 3088319 TI - [Lesions of the osteoarticular system in diabetes mellitus]. PMID- 3088320 TI - Technique for hand-rearing and reintroducing rejected cotton-top tamarin infants. AB - During a one year period, seven rejected cotton-top tamarin infants were hand reared. A hand-rearing program was developed which included the use of heated surrogates, a non-human primate infant formula, special nipples, and a systematic reintroduction into a family group. This regimen was quite successful. The hand rearing process yielded a success rate of 75.0%, while the reintroduction process had a success rate of 80.0% for reintroduction into a family group and 100.0% survival rate. PMID- 3088321 TI - Protein-bound plasma homocyst(e)ine and identification of heterozygotes for cystathionine-synthase deficiency. AB - We measured protein-bound plasma homocyst(e)ine in 15 normal adult subjects and nine heterozygotes for homocystinuria due to cystathionine beta-synthase deficiency. The mean (+/- SD) concentrations obtained in the two groups of subjects were 4.35 +/- 1.50 and 9.16 +/- 3.40 mumoll-1, respectively. The mean values were significantly different, although the levels of three heterozygotes overlapped those of the control range. This method allows preliminary screening of the heterozygotes for homocystinuria and can be carried out by laboratories that have only facilities for amino acid analysis. PMID- 3088322 TI - Pyruvate carboxylase deficiency in twins. PMID- 3088323 TI - High-performance liquid chromatographic assay of argininosuccinate: its application in argininosuccinic aciduria and in normal man. AB - Argininosuccinate (ASA) is determined in a few minutes with little manipulation by reversed phase high-performance liquid chromatography (HPLC) using O phthaldialdehyde. The two cyclic anhydrides of ASA are not formed during analysis but, if present, can be determined simultaneously. As little as 1 nl urine from a patient with argininosuccinic aciduria was sufficient for analysis; the ASA/creatinine ratio was 50.8 mmol g-1 and daily excretion was 5-7g ASA. We found small amounts of the two anhydrides in the patient's urine and we give factors to estimate, from their peaks, the corresponding amount of ASA. Urine from normal children showed a small acid-labile (at 100 degrees C) peak at the ASA position, which we tentatively assign to genuine ASA. From this peak less than 2mg ASA day 1 were excreted in our controls. Procedures for collection and storage of samples and the potential of this method for heterozygote detection are discussed. PMID- 3088324 TI - Osmolality of enteral formulas for maternal phenylketonuria. AB - Osmolalities of individual products and composite diets used in the treatment of maternal phenylketonuria were measured. Mathematical equations were developed which predict osmolality. Quantitative information on osmolalities of enteral formulas for women with maternal phenylketonuria may help clinicians plan diets to avoid the risk of gastrointestinal disturbances and to increase acceptability. PMID- 3088325 TI - A model for hyperphenylalaninaemia due to tetrahydrobiopterin deficiency. AB - A model for tetrahydrobiopterin deficiency in mice is described. Elevated levels of phenylalanine produced in the model were shown to be dramatically reduced after injection of tetrahydrobiopterin. A comparison of several reduced pterins for their efficacy in the system is described. The unnatural S isomer of tetrahydrobiopterin was shown to be active in the system. PMID- 3088326 TI - Thiamine non-responsive intermittent branched-chain ketoaciduria in a Laotian child. PMID- 3088327 TI - Niemann-Pick disease type B: clinical signs and follow-up of a new case. AB - A girl affected by Niemann-Pick disease type B is reported. The patient presented unusual skin lesions of nummular eczematous dermatitis, signs of delayed puberty and stunted physical development, together with the typical symptoms involving visceral organs and lungs. This disease may therefore indirectly affect more body organs than assumed. PMID- 3088328 TI - Accumulation of [3H]sialyl-conjugates in sialidosis (sialidase-deficient) fibroblasts cultured in the presence of [3H]-N-acetylmannosamine. AB - Skin fibroblasts from normal individuals and a patient with the infantile form of sialidosis were cultured for up to 72 h in medium containing [3H]-N acetylmannosamine. The sialidosis fibroblasts consistently accumulated more labeled compound(s) than the control cells, i.e. 37-88% more cpm per mg protein. Precipitation of sonicates of these cells with 10% trichloracetic acid, TCA, demonstrated that the excess radioactivity in the sialidosis fibroblasts was in one or more TCA soluble compounds. There was no detectable difference in the amount of label in the TCA insoluble material. The TCA soluble, labeled, material from the sialidosis and the control fibroblasts was separated, isolated and purified on AG1-X8, QAE Sephadex A-25 and Bio-Gel P-4 chromatography columns. Analysis of the isolated material showed the excess radioactivity in the sialidosis fibroblasts to be due to increased levels of [3H]sialic acid covalently bound to a variety of anionic sialyl conjugates. These compounds have been separated and partially purified. Finally, acid hydrolysis and chromatographic analysis of the TCA insoluble fractions showed that greater than 80% of the label in this material was also due to [3H]sialic acid. There was no detectable difference between the control and the sialidosis patient in the amount of label in this fraction. PMID- 3088329 TI - Beta-mannosidosis: prenatal detection of caprine allantoic fluid oligosaccharides with thin layer, gel permeation and high performance liquid chromatography. PMID- 3088331 TI - Fever: disguised friend. PMID- 3088330 TI - T cell differentiation within thymic nurse cells. AB - Thymic nurse cells (TNC), defined as in vitro isolation products of thymic tissue, are epithelial cells harboring in their cytoplasm up to 200 intact, actively dividing thymocytes which are completely surrounded by vacuolar membranes. The TNC plasma membrane expresses major histocompatibility complex class I (H-2 K/D) and class II (I-A) antigens. The expression of MHC class I and class II antigens on the TNC vacuolar membranes was investigated with an improved in situ labeling technique. The major histocompatibility complex phenotype of the vacuolar membranes is H-2 K/D+, I-A2+ and thus identical to the TNC plasma membrane phenotype. By using the labeling technique, the TNC thymocyte population was examined for expression of the T cell differentiation antigens Thy-1, peanut agglutinin, Lyt-1, and Lyt-2, and the antigen expression was related to resistance of this population to cortisone. The majority of TNC thymocytes in individual TNC were cortisone-sensitive and expressed the immature phenotype of cortical thymocytes (Thy-1hi, PNAhi, Lyt-1lo, Lyt-2). A minority of the TNC thymocytes were cortisone-resistant and expressed a mature phenotype (Thy-1lo, peanut agglutininlo, Lyt-1hi). The existence of this minor mature population was confirmed in vivo: cortisone-resistant thymocytes were associated with cortical epithelial cells scattered throughout the thymic cortex of mice treated with dexamethasone. The major histocompatibility complex positive microenvironment of TNC and the heterogeneity in phenotype and resistance to cortisone of the TNC thymocytes, which is related to the state of maturation, indicate that TNC play an important role in the selection and differentiation of T cells. PMID- 3088332 TI - Squamous cell carcinoma of the rectum: a multimodality approach. AB - A 60-year-old homosexual male with a diagnosis of squamous cell carcinoma of the rectum, arising 7 cm from the dentate line, was treated with a rectal preserving multimodality approach consisting of excisional biopsy and chemotherapy with 5 fluorouracil (5-FU) and mitomycin-C with concomitant administration of radiation therapy to the tumor and pelvic nodal bearing areas. The patient has remained disease-free with full preservation of anorectal function on follow-up at 2 years. This approach to a difficult and unusual problem is recommended as a first line of therapy rather than surgical resection if it is deemed that the patient can tolerate a combination of chemo and radiation therapy and the patient will be able to participate in a long-term follow-up. PMID- 3088333 TI - Leiomyosarcoma of the anus treated with sphincter-preserving surgery and radiation therapy. AB - The sixth published case of a leiomyosarcoma of the anus is reported and the previous literature reviewed. Treatment with successful preservation of anal sphincter function is described. Local excision of the tumor was followed by external beam radiation therapy and an Iridium-192 implant. The details and rationale for this mode of therapy for resectable anal tumors are discussed. PMID- 3088334 TI - Pericardial heterografts. Toward quality control of the mechanical properties of glutaraldehyde-fixed leaflets. AB - The mechanical properties of five different, equally distributed, and randomly oriented sites in natural and glutaraldehyde-fixed calf pericardial sacs were investigated. Identical sites in different sacs were obtained by placing a template over each sac and using the ligaments still attached to the pericardium as a reference frame. Mean maximum extension of the fixed tissue was statistically significantly greater than that of natural tissue at the same degree of stress. There was no significant difference in thickness from position to position within a sac, from sac to sac, or from the natural to fixed pericardium. However, the extensibility of one particular site was significantly greater than that of other positions in the pericardial sac. This position lay entirely in a well-defined sector that emanated radially from the pericardial ligaments. Light and electron microscopy showed no difference in collagen structure in the five positions studied. In contrast, both the content and ultrastructure of the tissue elastin differed in the region of high extensibility compared with those sites studied in the remainder of the sac. This region contained coarse condensed elastin whereas the other sites had fine elastin dispersed diffusely throughout the tissue. These results suggest that pericardial heterografts of uniform thickness may be harvested from any position in calf pericardium. However, unless the region of coarse condensed elastin is excluded, leaflets with significantly different mechanical properties may be produced. PMID- 3088335 TI - Ultrastructural study comparing the efficacy of five different methods of intraoperative myocardial protection in the human heart. AB - The quality of myocardial protection during cardiac arrest in cardiac operations was investigated in 310 patients. Eighty patients underwent aortic valve replacement and 230 had coronary artery bypass grafting. Four different cardioplegic solutions (Kirsch, Bretschneider, St. Thomas' Hospital, and Hamburg) and the method of induced fibrillation were tested by ultrastructural analysis of the degree of ischemic injury at the end of the cardiac arrest period. Hypothermia was identical in all five groups. In this study, subendocardial and subepicardial needle biopsies were evaluated by a standardized scoring system. Chemical cardioplegia produced mainly moderate ultrastructural injury independent of the time of ischemia. Kirsch cardioplegia and the intermittent fibrillation procedure produced ischemic injury of greater and unpredictable severity. Only with Kirsch cardioplegia was a correlation observed between the duration of intraoperative arrest and the degree of injury, which is indicative of a lack of myocardial protection. The tolerance to ischemia was significantly better in patients undergoing bypass grafting than in those with aortic valve disease and therefore longstanding hypertrophy. In conclusion, the Bretschneider, St. Thomas' Hospital, and Hamburg solutions provide satisfactory myocardial protection but are not able to completely prevent myocardial ischemic injury. Kirsch cardioplegia and the intermittent fibrillation procedure provide insufficient myocardial protection. Patients with left ventricular hypertrophy are at a greater risk during cardiac operations than patients undergoing coronary bypass operations. PMID- 3088336 TI - Nutrition in acute respiratory failure. PMID- 3088337 TI - Pathogenesis of silicosis: current concepts and hypotheses. PMID- 3088339 TI - Lidocaine increases lung uptake of propranolol. PMID- 3088340 TI - Inhibition of soybean lipoxygenase-1 by 10-butyryl substituted 1,8-dihydroxy-9 anthrone (butantrone). AB - 10-Butyryl substituted 1,8-dihydroxyanthrone (butantrone) inhibited soybean lipoxygenase-1 irreversibly and more efficiently than its parent compound 1,8 dihydroxyanthrone (dithranol, anthralin) (IC50 values 0.090 mM and 1.1 mM, respectively). Intact butantrone rather than its hydrolysis product was the primary effector and the 10-butyryl moiety its site specific probe, probably directing the inhibitor to the proximity of the binding site of the lipid substrate/product. PMID- 3088338 TI - Lactate metabolism in fetal type II pneumocytes. PMID- 3088341 TI - The Municipal Health Services Program. Improving access to primary care without increasing expenditures. AB - Under the Municipal Health Services Program (MHSP), five city governments created networks of primary care clinics with a goal of serving populations thought to have poor access to primary medical care. A major concern was fragmented care in public hospitals and other public facilities. The new MHSP clinics were expected to provide care at lower cost than the population's alternative sources of care. Medicare and Medicaid waivers were also provided. This evaluation indicates that MHSP did reach most, but not all, of the targeted groups. MHSP may have successfully replaced some outpatient department and emergency room services. However, it failed to realize the program goals of continuity and high patient satisfaction. Per capita expenditures for medical care for MHSP users were no higher than for others, but also were not significantly lower. However, for Medicare eligible MHSP users, expenditures by Medicare were significantly less. PMID- 3088342 TI - Profits under pressure. The economic performance of investor-owned and nonprofit health maintenance organizations. AB - This study assesses the economic performance of investor-owned and private nonprofit health maintenance organizations by comparing their costs and revenues, controlling for other characteristics of the plans and the areas in which they are located. Data are drawn from a sample of 173 HMOs operating in 1983, one quarter under proprietary auspices. For-profit plans have average costs 10% higher than their nonprofit counterparts, primarily due to higher expenses for ambulatory care. Average revenues are also higher in investor-owned HMOs, although this difference is one third the size of the estimated difference in costs. The paper concludes with a discussion of the implications of these findings for both the future performance of the HMO industry and public policy affecting prepaid health care. PMID- 3088343 TI - Impact of the New York Long-Term Home Health Care Program. AB - The Long-Term Home Health Care Program (LTHHCP), also known as the Nursing Homes Without Walls, is an innovative, comprehensive Medicaid program in New York State that provides nursing home level of care to patients at home. This paper evaluates the performance of the first nine LTHHCP sites over the first 2 years of operation. Across all sites there is clear evidence that the program has been extremely successful in reducing levels of nursing home utilization. In the five upstate sites, considerable cost savings have also been achieved while improving patient survival. In the four New York City sites, patient outcomes have also been favorable, but health care costs for clients have been higher than would have been the case had clients not enrolled in the LTHHCP. Across the entire state, results could have been better if enrollment had been targeted to subsets of the eligible patient groups for whom the LTHHCP is most cost effective. PMID- 3088344 TI - [Treatment of panhypopituitarism]. PMID- 3088345 TI - [Spontaneous development from Waldenstrom's macroglobulinemia to immunoblastic sarcoma]. PMID- 3088346 TI - In vitro activity of aztreonam against gram negative bacteria from clinical specimens and its comparison with other commonly used antibiotics. AB - A total of 755 gram negative bacteria isolated from clinical specimens were tested against aztreonam by the disc agar diffusion test. The strains of bacteria used in this study consisted of Escherichia coli (314), Enterobacter aerogenes (30), E. agglomerans (7), E. cloacae, (39), Citrobacter diversus (9), C. freundii (13), Hafnia alvei (3), Acinetobacter calcoaceticus (10), Klebsiella oxytoca (6), K. ozaenae (5), K. pneumoniae (107), Morganella morganii (3), Moraxella sp. (10), Pasteurella multocida (1), Proteus mirabilis (66), P. vulgaris (4), Providencia rettgeri (12), P. stuartii (5), Pseudomonas aeruginosa (85), P. fluorescens (2), P. maltophila (7), Salmonella sp. (1) and Serratia marcescens (17). In vitro activity against aztreonam was compared with amikacin, ampicillin, carbenicillin, cephalosporin, cefoxitin, chloramphenicol, gentamicin, nitrofurantoin, piperacillin, tetracycline, sulfamethoxazole-trimethoprim and tobramycin. Over 99% of E. coli and Enterobacter species were susceptible to aztreonam. All the 118 strains of Klebsiella, 87 strains of Proteus-Providencia and 17 strains of S. marcescens were also susceptible. Aztreonam also showed good activity against P. aeruginosa, inhibiting 90% of the 85 isolates tested. PMID- 3088347 TI - Head and neck manifestations of neurofibromatosis. AB - Neurofibromatosis is a neurocutaneous systemic disease that occurs in 1:2500 to 3300 live births. Prevalence figures have shown it to be as common as cystic fibrosis or Down's syndrome and more than twice as common as muscular dystrophy. In this study, our experience with 257 cases of neurofibromatosis seen since 1972 is reviewed. Intracranial, bony, and extracranial anomalies are described in the 223 patients (87%) who presented with, or ultimately developed, head and neck manifestations of the disease. The most common intracranial tumor was optic glioma, found in 35 patients (14%), 19 younger than 10 years of age. Acoustic neuromas were diagnosed in eight individuals (3%) and were bilateral in three. The most common skull anomaly was macrocephaly, noted 78 times (30%). Absence of the sphenoid wing occurred in 11 patients (4%) and 19 others (7%) had facial asymmetry due to other skull abnormalities. Extracranial manifestations included neurofibromas of the plexiform and nonplexiform type, Lisch nodules, and cafe-au lait spots. PMID- 3088348 TI - Potencies of diazepam metabolites in rats trained to discriminate diazepam. AB - The dose-response relationships of diazepam and several of its metabolites were determined in rats trained to discriminate diazepam (3 mg/kg) from saline in a two-lever operant choice task. Generalization of the diazepam stimulus was found to occur with temazepam and oxazepam, which were nearly equipotent with diazepam, and also with desmethyldiazepam, which was about half as potent as diazepam. The hydroxylated metabolites, 4'-hydroxydiazepam and 4'-hydroxydesmethyldiazepam were inactive in doses up to 12 mg/kg. These results show that some diazepam metabolites are quite potent behaviorally and indicate the possibility that these metabolites may contribute to the pharmacological effect of diazepam in vivo. PMID- 3088349 TI - Transient contralateral rotation following unilateral substantia nigra lesion reflects susceptibility of the nigrostriatal system to exhaustion by amphetamine. AB - Following unilateral 6-OHDA induced SN lesion, a transient period of contralateral rotation has been reported to precede the predominant ipsilateral circling. In order to clarify the nature of this initial contralateral rotation we examined the effect of the duration of recovery period after the lesion, on amphetamine-induced rotational behavior. Three days post lesion, most rats circled predominantly contralaterally to the lesion. Such contralateral rotation may result from either degeneration-induced breakdown of the DA pool, or lesion induced increase of DA turnover in the spared neurons. A substantial degree of contralateral preference was still evident when amphetamine was administered for the first time 24 days after lesioning, indicating involvement of spared cells in the contralateral rotation. However, regardless of the duration of recovery (and irrespective of either lesion volume, amphetamine dose, or post-lesion motor exercise), amphetamine-induced rotation tended to become gradually more ipsilateral as the observation session progressed, and all rats circled ipsilaterally to the lesion in response to further amphetamine injections. These findings suggest that amphetamine has an irreversible effect on the post-lesion DA pool contributing to contralateral rotation. PMID- 3088350 TI - Inhibin activity and secretion of gonadotropin during the period of follicular maturation. AB - To evaluate the relative contributions of the ovarian inhibin and estradiol-17 beta (E) on the regulation of FSH secretion, inhibin and E in ovarian venous plasma (OVP) and FSH and LH in peripheral plasma were simultaneously measured using superovulating rats with special reference to follicular maturation. By the transplantation of a pituitary gland from adult male rats under the kidney capsule between 1100 and 1200 hr on diestrus-1 in cyclic rats, superovulation was successfully induced on the morning of the next estrus without any additional treatment with human chorionic gonadotropin (hCG). The number of maturing follicles capable of ovulating in response to hCG significantly increased at 12 hours after the grafting as compared with sham-operated controls and further increases occurred until the afternoon of proestrus. In the superovulating rat, first and second surges of FSH were completely blocked and an LH surge was also partially suppressed during the periovulatory period when surges of FSH and LH were normally observed in controls. Contents of FSH as well as LH in the animal's own pituitary gland were suppressed significantly after the grafting as compared with controls. A marked increase in inhibin activity in OVP of rats with a pituitary transplant occurred concomitantly with an increase in the number of follicles capable of ovulating whereas E levels in OVP did not so. Inhibin activity in OVP at each point was much higher in the pituitary grafted rats than in controls but this was not true for E levels. These results suggest that ovarian inhibin derived from the maturing follicles rather than E may be a primary factor for regulation of FSH secretion, and high levels of endogenous inhibin can suppress synthesis of LH as well as FSH in the pituitary gland of the female rat. PMID- 3088351 TI - Age-related differences in the pituitary prolactin response to thyrotropin releasing hormone. AB - We have previously reported that human subjects undergoing surgery for inguinal hernias exhibit an age-related attenuation in the plasma prolactin response, with no differences during resting conditions. We suggested that these differences were due to age-related neuroendocrine changes, but that peripheral factors may play a role as well. In the present study, we have assessed the pituitary response to 500 micrograms of thyrotropin-releasing hormone (TRH) in the very same subjects previously studied during surgery. Blood samples were drawn immediately prior to, as well as 10, 20, 40 and 60 minutes following the intravenous administration of TRH. There was a clear-cut age-related attenuation in the pituitary prolactin response with no difference in the thyrotropin (TSH) response. Maximum prolactin response in the young subjects was 31.7 micrograms/l and 19.2 micrograms/l in old subjects (F(4) = 3.5, p less than .01, two-way ANOVA). These results indicate that the age-related differences in the prolactin response to stress are mainly due to pituitary changes. However, prolactin secreting cells are under the control of the hypothalamus. Therefore, the possibility must be considered that aging or other concurrent factors could be exerting their influence via the hypothalamus and not necessarily directly at the pituitary level. PMID- 3088353 TI - Using intuitive knowledge to make clinical decisions. PMID- 3088354 TI - Albuterol: a selective beta 2 bronchodilator. PMID- 3088355 TI - Overdue delivery: its impact on mothers-to-be. PMID- 3088356 TI - A comparison of orthopedic casts: breaking the mold. PMID- 3088357 TI - The painless pelvic. PMID- 3088352 TI - Mitochondrial membrane fatty acid composition in the marmoset monkey following dietary lipid supplementation. AB - Diets supplemented with high levels of saturated fatty acids derived from sheep kidney (perirenal) fat or unsaturated fatty acids derived from sunflowerseed oil were fed to marmoset monkeys for 22 wk. The effect of such diets on plasma, red blood cell phospholipids, and liver, heart, kidney and brain mitochondrial phospholipid fatty acids was determined. Despite large differences in the level and type of lipid present in the experimental diets, there was little effect on the proportion of saturated to unsaturated fatty acids in the phospholipids of the membranes examined. The diets did, however, alter the proportion of the various classes of polyunsaturated fatty acids in the membrane phospholipids, with the sunflowerseed oil diet elevating and the sheep kidney fat diet reducing the n-6/n-3 unsaturated fatty acid ratio, relative to a low (mixed fat) reference diet. This change occurred in all membranes except brain, in which only a small response to altered dietary lipid intake was observed. Elevation of dietary linoleic acid led to an increase in membrane linoleic acid and a marked decrease in membrane arachidonic acid, such that the membranes from animals fed the sunflowerseed oil diet exhibited the lowest proportion of arachidonic acid. In this latter respect, the response of the marmoset monkey to dietary lipid supplementation differs markedly from the rat. Our inability to alter significantly membrane lipid saturation/unsaturation supports the notion that a homeostatic mechanism is in some way responsible for buffering membranes from the effects of significant changes in the nature of the dietary lipid intake. PMID- 3088358 TI - Intrauterine transfusion for severe isoimmunization. PMID- 3088359 TI - Grandparents in NICUs. PMID- 3088360 TI - SIADH and the acutely ill child. PMID- 3088361 TI - Send in the clown: a reminder. PMID- 3088362 TI - Patient education: implementation. PMID- 3088363 TI - Malpractice suits: implications for obstetric nurses. PMID- 3088364 TI - Research utilization: the clinician's role. PMID- 3088365 TI - The politics of patienthood. PMID- 3088366 TI - Maternal versus fetal rights: implications for nurses. PMID- 3088367 TI - Sodium bicarbonate during CPR. PMID- 3088368 TI - Design for successful patient teaching. PMID- 3088369 TI - Childbirth classes for couples desiring VBAC (vaginal birth after cesarean). PMID- 3088370 TI - New-parent teaching in the ambulatory care setting. PMID- 3088371 TI - The cyanotic child: heart defects and parental learning needs. PMID- 3088372 TI - Yours, mine, and ours: stepparents and their children. PMID- 3088374 TI - Creating a motivating climate. Patient teaching. PMID- 3088373 TI - Preventing neonatal hepatitis-B infection. PMID- 3088375 TI - Research in clinical settings. PMID- 3088376 TI - [Radioimmunologic determination of the molecular variation of human thyroxine binding globulin]. PMID- 3088377 TI - Implications of air pollution effects on athletic performance. AB - Both controlled human studies and observational studies suggest that air pollution adversely affects athletic performance during both training and competition. The air pollution dosage during exercise is much higher than during rest because of a higher ventilatory rate and both nasal and oral breathing in the former case. For example, sulfur dioxide, which is a highly water-soluble gas, is almost entirely absorbed in the upper respiratory tract during nasal breathing. However, with oral pharyngeal breathing, the amount of sulfur dioxide that is absorbed is significantly less, and with exercise and oral pharyngeal breathing a significant decrease in upper airway absorption occurs, resulting in a significantly larger dosage of this pollutant being delivered to the tracheobronchial tree. Recently, several controlled human studies have shown that the combination of exercise and pollutant exposure (SO2 or O3) caused a marked bronchoconstriction and reduced ventilatory flow when compared to pollution exposure at rest. In a situation like the Olympic Games where milliseconds and millimeters often determine the success of athletes, air pollution can be an important factor in affecting their performance. This paper examines possible impacts of air pollution on athletic competition. PMID- 3088378 TI - The U.S. Olympic Committee experience with exercise-induced bronchospasm, 1984. AB - Exercise-induced bronchospasm is a medical deterrent to an athlete's natural ability to perform. The U.S. Olympic Committee has met the challenge of recognizing and dealing with this common yet unappreciated medical complication aggravated by athletic exertion. Prior to the 1984 Los Angeles Olympic Games the U.S. Olympic Committee developed a screening program to identify members of its Olympic team who suffered from asthma or exercise-induced bronchospasm. The screening identified 67 of 597 Olympic athletes with asthma or exercise-induced bronchospasm. Coordination of medical care by contact between members of the American Academy of Allergy and Immunology, the U.S. Olympic Committee Chief Medical Officer, the athlete's personal physician, and the athlete was done. Medications approved for use in these conditions by the International Olympic Committee Medical Commission policies were prescribed. Forty-one medals were won by this group of handicapped athletes. Their example will raise the hopes and aspirations of countless young allergic and asthmatic children who dream of the thrills and health benefits of physical performance at almost any level of competition. PMID- 3088379 TI - Prevention with and without the use of medications for exercise-induced asthma. AB - Exercise-induced asthma or bronchospasm occurs in approximately 12% of the population. It can be prevented with proper techniques of exercise and environmental exposures and with medication. Exercise techniques include timing of exercise to less than 5-min interludes and continued repeat exercise every hour. Exercising to less than full tolerance may avoid the onset of exercise induced asthma. In some individuals exercise in warm, humidified air is less asthmogenic than in dry, cold air. Medications that are effective and safe include bronchodilators such as theophylline and beta-agonists and prevention with cromolyn sodium in the atopic or sulfite exposed individual. PMID- 3088380 TI - Mechanisms and patterns of blood lactate increase during exercise in man. AB - The close balance between the O2 requirement to perform exercise and the O2 supply was analyzed. A non-uniform capillary PO2 can result in anaerobic metabolism in some muscle fibers despite an apparently adequate mean capillary PO2. The pattern of lactate increase for constant work rates and incremental exercise is described. Lactate increases without an increase in pyruvate at a threshold work rate above which the lactate/pyruvate ratio increases. The latter decreases immediately at the start to recovery. From simultaneous measurements of arterial lactate and pyruvate during exercise and recovery, we conclude that the lactate increase at the lactate threshold is consequent to a change in redox state rather than a mass action effect. PMID- 3088381 TI - [Pulmonary manifestations of schistosomiasis]. AB - Pulmonary manifestations are not frequent. They may occur at any stage of the parasitic cycle. Acute manifestations are concurrent with the parasitic toxemia stage and suggests an immunoallergic mechanism. Acute pulmonary heart is exceptional. Chronic manifestations are the consequence of egg-laying and are dominated by chronic pulmonary heart. Treatment is based on current antischistosomal drugs but their effectiveness is only evident in parasitic toxemia stages. PMID- 3088382 TI - [Effect of N-ethyl-N-nitrosourea on the liver ultrastructure. I. Activity of the cytochrome P-450-dependent hepatic monooxygenase system]. AB - Effects of N-ethyl-N-nitrosourea (ENU) on cytochrome P-450-dependent monooxygenase system activity and the ultrastructure of the liver cells are examined. Significant changes in the structure of mitochondria, smooth and rough endoplasmic reticulum and Golgi apparatus are observed, particularly in 3rd zone of acinus. Cytochrome P-450 and monooxygenase activity shows decrease, but cytochrome b5 and NADH-cytochrome b5 reductase activity increases. PMID- 3088383 TI - Purification of IgG monoclonal antibodies from ascitic fluid based on Rivanol precipitation. PMID- 3088384 TI - Purification of rat monoclonal antibodies. PMID- 3088385 TI - Preparation of F(ab')2 fragments from mouse IgG of various subclasses. PMID- 3088386 TI - Optimal conditions for the preparation of proteolytic fragments from monoclonal IgG of different rat IgG subclasses. PMID- 3088387 TI - Ultrasensitive cooperative immunoassays with mixed monoclonal antibodies. PMID- 3088388 TI - Immunohistological studies with monoclonal antibodies. PMID- 3088389 TI - Use of alkaline phosphatase-conjugated antibodies for detection of protein antigens on nitrocellulose filters. PMID- 3088390 TI - Isolation and characterization of apolipoproteins A-I, A-II, and A-IV. AB - A number of different analytical techniques are now available for the isolation of apoA-I, apoA-II, and apoA-IV. The choice of a particular technique is dependent on the instrumentation available, and the quantity of isolated apolipoprotein required. The isolation and characterization of the separate isoforms and the precursor isoproteins of the individual apolipoproteins are detailed, and methods for the evaluation of the purity of the separate apolipoproteins presented. A method for the evaluation of apolipoproteins in plasma is now available which permits the identification of structural variants of plasma apolipoproteins in patients with dyslipoproteinemias. PMID- 3088391 TI - Genetic polymorphism in the ApoA-I/C-III complex. PMID- 3088392 TI - Molecular cloning and sequence analysis of human apolipoprotein A-II cDNA. PMID- 3088393 TI - Rat apolipoprotein A-IV: application of computational methods for studying the structure, function, and evolution of a protein. AB - There are a great variety of computational methods available to study protein and nucleic acid sequences. The choice of a computer program appropriate to a particular problem and the critical interpretation of the results can lead to specific, and experimentally testable, predictions of a protein's structure and function and may yield insights into its evolution and the location of its gene. We have shown that rat apoA-IV bears a striking structural similarity to human apoA-I (summarized in Fig. 7). Statistical analyses of homologies between apolipoproteins A-I, A-IV, and E demonstrate conclusively that all three sequences diverged from a common ancestral gene. That apoA-IV largely composed of 22 amino acid amphipathic segments with alpha-helical potential suggests that it possesses the structural requirements for LCAT activation. Analysis of the apoB, E receptor-binding domain of human apoE3 has demonstrated that it evolved from an ancestral repeated sequence. Assuming that the genes for these proteins evolved as a result of a series of intra- and intergenic unequal crossovers, it is likely that their genetic loci were at one time linked. The repeated sequences of which these genes are composed have propagated themselves in an expansionary manner. Given this fact, the existence of other genes or pseudogenes based upon this repeated sequence motif is a distinct possibility. PMID- 3088394 TI - Detecting internally repeated sequences and inferring the history of duplication. PMID- 3088395 TI - Metabolism of apolipoproteins A-I, A-II, and A-IV. PMID- 3088396 TI - Methods for assessment of tissue sites of lipoprotein degradation. PMID- 3088397 TI - Effects of Lactobacillus casei on Pseudomonas aeruginosa infection in normal and dexamethasone-treated mice. AB - A single intraperitoneal injection of Lactobacillus casei YIT 0003 into normal or dexamethasone-treated mice led to nonspecific resistance against intraperitoneal challenge with lethal doses of Pseudomonas aeruginosa PAO 3047. The enhanced resistance was retained for 14 days (P less than 0.05) after injection with living L. casei. In contrast, the statistically significant duration of the enhanced resistance in mice treated intraperitoneally with living L. acidophilus YIT 0075 was only 5 days. The in vivo killing activity of peritoneal exudate cells (PECs) against P. aeruginosa 5 and 7 days after intraperitoneal injection of living L. casei was significantly higher than in the case of PECs elicited by L. acidophilus. In the case of intravenous injection of heat-killed L. casei before intraperitoneal challenge with P. aeruginosa, there were no survivors in the late period after administration of L. casei. A high correlation existed between the patterns of in vivo killing of P. aeruginosa by PECs and survival rate of mice injected intravenously with heat-killed L. casei. The reduced in vivo killing activity of PECs from dexamethasone-treated mice against P. aeruginosa infection was also augmented by the intraperitoneal injection of heat killed L. casei. These results indicate that L. casei possesses a resistance enhancing capacity against P. aeruginosa infection in vivo. Differences in the duration of the enhanced resistance caused by L. casei and by L. acidophilus may be due to differences in chemical composition and/or physicochemical properties of the cell walls of the two kinds of bacteria. PMID- 3088398 TI - Laser Raman spectroscopy of lyophilized bacterial spores. AB - Laser-excited Raman spectra were examined in lyophilized spores of Bacillus cereus. In a comparison of the spectrum of the dormant spore with that of the germinated spore, we found several Raman bands which occurred in the former but not in the latter. Among these Raman bands, the 1,573, 1,395, 1,017, 822, and 662 cm-1 bands were assigned to the vibrational frequencies of calcium dipicolinate (CaDPA). No Raman bands and peaks due to dipicolinic acid (H2DPA) were observed. This Raman evidence indicates that CaDPA is the predominant DPA species in this spore. We also proposed a tentative assignment for other vibrational frequencies due to several components of the spore. PMID- 3088400 TI - Inherited deficiency of the seventh component of complement associated with meningococcal meningitis: lack of serum bactericidal activity against Neisseria meningitidis in a girl with C7 deficiency and HLA studies of a C7-deficient Japanese family. AB - An 8-year-old girl with meningococcal meningitis lacked serum complement activity. The seventh component of complement (C7) could not be detected in her serum by either functional or immunochemical analysis. The levels of the other components were within the normal range. Her serum complement activity was restored by the addition of purified C7. Her fresh serum showed a total absence of bactericidal activity against Neisseria meningitidis, group Y, but her serum bactericidal activity was restored by the addition of purified C7. The restoration of her serum bactericidal activity was completely inhibited in the presence of Mg2+ EGTA. These findings suggest that restoration of the bactericidal activity of her serum against N. meningitidis might be mediated by the specific antibody against N. meningitidis and the reconstituted complement system in her serum. Heterozygous deficiency of C7 was found in 10 of her family members. Genetic studies showed that the mode of inheritance might be an autosomal codominant trait. No genetic linkage between deficiency of C7 and the HLA system was found. PMID- 3088399 TI - Determination of the T-cell subset producing gamma-interferon in tuberculous pleural effusion. AB - The percentage of cells of different T-cell subsets and their functions in tuberculous pleural effusion were investigated. The percentage of OKT4-positive cells was 65 +/- 2% (mean +/- SEM, n = 8) and that of OKT8-positive cells was 19 +/- 3% (n = 8). Pleural T lymphocytes of patients with tuberculous pleurisy responded well to stimulation with purified protein derivative of tuberculin, and deoxyribonucleic acid synthesis was observed along with gamma interferon (IFN gamma) production. When pleural T lymphocytes of patients with tuberculous pleurisy were treated with OKT4 monoclonal antibody and complement, a significant decrease in IFN-gamma production was observed in all eight patients (P less than 0.005), whereas no definite decrease in IFN-gamma production was found after treatment with OKT8 monoclonal antibody and complement. These results suggest that at least the OKT4+/OKT8- T-cell subset is responsible for the antigen specific IFN-gamma production in pleural T lymphocytes of patients with tuberculous pleurisy. PMID- 3088401 TI - [Comparison of the Gruber-Widal and ELISA technics used to study Salmonella typhi and Salmonella paratyphi infections in patients]. AB - In this study, antibody levels were determined against the agents of typhoid and paratyphoid fever in 168 patient's sera and 40 healthy control sera by Gruber Widal and ELISA techniques. We compared the results of these two techniques, and discussed. The needed antigens for both techniques were prepared from the local strains of the agents of these infections which were isolated in our laboratory. The widal's tube agglutination test was carried out by classical method, and the ELISA technique was done by the method of Woller et al. As a result, we found that the titers obtained by ELISA were as 4-6 times higher as than those of Widal's. Additionally nonspecific reactions were less seen in ELISA than in Widal. PMID- 3088402 TI - The nature of the scrapie agent. AB - There now seems little doubt that the infective agent of scrapie cannot be accommodated within current concepts of virology/molecular biology. It is proposed: that the basic infective entity is a nucleic acid fragment (oligonucleotide) of some 40 bp coupled with specific (but host encoded) protein totalling approximately 10(5) daltons, a significant proportion of which is in the form of proteolipid; that the nucleic acid fragment reprograms the host cell on the chemically switched microprocessor network analogy already proposed; that the nucleic acid fragment has no initiation sequence for replication: it is therefore non-infective; that the nucleic acid fragment can replicate when associated with the specific protein component because the resulting complex is able to displace mobile genetic element flanking sequences (similar to the yeast delta sequence). The function of the protein is to provide a scaffolding which allows the nucleic acid fragment to be assimilated into the replication cycle of the mobile genetic element as a whole. PMID- 3088403 TI - The potential use of vitamin E and selenium in parkinsonism. AB - Parkinson's disease (PD) is a chronic neurodegenerative illness which affects a significant number of the older population. Its treatment, which consists mostly of the dopamine precursor, L-Dopa, is associated with various complications. Research which has been conducted in order to develop drugs which might be without these toxic side-effects has not so far been met with a great degree of success. Recently the development of a parkinson-like syndrome in addicts who were using the compound methyl-phenyl-pyridine has refocused attention on the possible participation of free radicals in the etiology of PD. Herein it is postulated that the use of the free radical scavengers, vitamin E and selenium, might be effective in the early treatment of PD and might help to circumvent some of the complications associated with agonists therapy. PMID- 3088404 TI - Prospects for a vaccine against malaria. PMID- 3088405 TI - Pure red cell aplasia associated with acute lymphoblastic leukaemia of pre-T-cell origin. PMID- 3088406 TI - Nutrition of aboriginal infants and children in the Murray Valley. AB - A cross-sectional anthropometric study of 297 Aboriginal children aged from 0 to 11 years, from four communities in the Murray Valley region of north-western Victoria and south-western New South Wales, revealed significant levels of growth retardation compared with 146 local non-Aboriginal children. Mild, moderate and severe levels of malnutrition (according to anthropometric criteria) and high proportions of infants who were small for gestational age were found among the Aboriginal children. Levels of moderate malnutrition varied from 11% to 26% according to the standards of housing, the degree of community organization and the social pressures that were experienced by each community. The implications of these findings are discussed in terms of Aboriginal participation in primary health care. PMID- 3088407 TI - Mupirocin activity against methicillin-resistant Staphylococcus aureus. PMID- 3088408 TI - Misleading aetiological diagnosis of bacteraemia. PMID- 3088409 TI - Questionable role of mononuclear phagocytes in the elimination of lymphocytic choriomeningitis virus from spleens of acutely infected mice. PMID- 3088410 TI - Estimated spectrum of a 4-MV therapeutic beam. AB - We have made a comparative investigation of the estimated spectra obtained by the Laplace transform analysis of the transmitted exposure data measured in an absorption study of a 4-MV x-ray beam. Four transform pair models currently used with this method have been evaluated. It has been determined that the Archer Wagner model provides a valid representation of the measured transmission data and yields an estimated spectrum which most closely resembles a Monte Carlo spectrum calculated for a 4-MV therapeutic x-ray beam available from a typical medical accelerator. PMID- 3088411 TI - Measurement and calculation of neutron leakage from a medical electron accelerator. AB - The leakage neutron spectra and dose equivalent were systematically measured in the irradiation field, treatment room, maze, and outside the shielding door at the microtron medical electron accelerator facility of the National Cancer Center, Tokyo. For these measurements, we used two types of multimoderator neutron spectrometers (Bonner spheres containing indium activation detectors and 3He detector), an aluminum activation detector, and a commercially available neutron rem counter. The measured results were compared with the combined calculation of the one-dimensional ANISN and two-dimensional DOT3.5 discrete ordinates transport codes. The calculation was performed by using a measured source spectrum in the irradiation field and by computer modeling of the maze entrance. The calculation indicated good agreement in spectral shape and agreement with experiment within a factor of 2 in absolute dose-equivalent values. This transport calculation was systematically repeated for different geometrical and material parameters, and simple analytical formulas and their parameters applicable for shielding design of a medical electron accelerator facility were obtained in general form. PMID- 3088412 TI - Output factors and dose calculations for blocked x-ray fields. AB - Output factors for blocked fields have been measured in a polystyrene phantom for four collimator field sizes and two blocking schemes using 6-MV x rays. For all measurements the phantom surface was at the calibration source-surface distance (SSD) because, as is shown, the calculation of dose to any point in a phantom at an arbitrary SSD can be expressed in terms of the output factor for the field size at the calibration distance. It is found that output factors are a function of both the surface field size of the blocked field and the collimator field size. Specifically, the output factor for a blocked field is less than that for the collimator field size used but greater than that for an unblocked field of the same surface field size formed by collimator settings only. A method is proposed for utilizing these data to calculate the output factor for any collimator and blocked field size. The validity of the method is checked by using it to calculate dose to a point in a phantom and comparing this to the measured dose. PMID- 3088413 TI - Off-center ratios for three-dimensional dose calculations. AB - A new method is proposed for computing the off-center ratios (OCR's) in three dimensional dose calculations. For an open field, the OCR at a point is computed as the product of the primary OCR (POCR) and the boundary factors (BF's). The POCR describes the beam profile for an infinite field, that is, without the effect of the collimators. It is defined as the ratio of the dose at a point off the central ray to the dose at the point on the central ray at the same depth for an infinite field. The POCR is a function of radial distance from the beam central ray and depth. The BF describes the shape of the beam in the neighborhood of the field boundary defined by the collimators. It is defined as the ratio of the OCR at a point for a finite field to the OCR at the same point for an infinite field. The BF is a function of distance from the field boundary, depth, and field size. For a wedged field, we assume that the boundary factors remain the same as for open fields but the POCR's are altered. The changes in beam profiles are described by a factor called the wedge profile factor (WPF), defined as the ratio of the dose at a point for the largest wedged field to the dose at the same point for an open field of the same field size. The WPF is a function of lateral distance from the beam central plane and depth. Calculated OCR's using this new method are in agreement with the measured data along both the transverse and the diagonal directions of the field. PMID- 3088414 TI - Film dosimetry of small electron beams for routine radiotherapy planning. AB - The characteristics of very small fields, 1 X 1 and 2 X 2 cm, of electron beams of nominal energies, 5, 7, 10, 12, 15, and 18 MeV have been studied and compared to a 10 X 10 cm field. A parallel-plate ion chamber and film have been used to obtain various dose parameters. The central axis depth dose measurements, field flatness, uniformity index, and relative output factors are presented. It was found that satisfactory results for determining the relative output factor can be obtained from film data using a scanning densitometer. It is our conclusion that film dosimetry is acceptable in determining the necessary clinical parameters needed to treat patients with fields as small as 2 X 2 cm. For the 1 X 1 cm field size and for the electron energies greater than 10 MeV, there was substantial disagreement between the ion chamber and film data in the buildup region as well as the regions beyond the depth of maximum dose to the depth of 90% dose. PMID- 3088416 TI - Fine-needle aspiration biopsy of solitary thyroid nodules. Effect on cost of management, frequency of thyroid surgery, and operative yield of thyroid malignancy. PMID- 3088415 TI - Effect of a radiographic contrast agent on renal function in the rat. Comparison with equiosmolar mannitol. AB - The renal effects of the radiographic contrast agent meglumine iothalamate (Conray; C) were evaluated in rats. C produced a 42% fall in glomerular filtration rate (p less than 0.05) and a 44% fall in effective renal plasma flow (p less than 0.05). The effects of C were blunted by both acute and chronic volume expansion. Equiosmolar mannitol produced similar hemodynamic responses as C. The fractional excretions of sodium and potassium were similar in rats given C or mannitol. The renal effects of C appear to be due to its hypertonicity. These effects may be modified by volume expansion. PMID- 3088417 TI - Cost effective use of supplies in the NICU. PMID- 3088418 TI - Acanthamoeba keratitis associated with contact lenses--United States. PMID- 3088419 TI - Bacillus cereus--Maine. PMID- 3088420 TI - Bacteremia associated with reuse of disposable hollow-fiber hemodialyzers. PMID- 3088421 TI - Fatality at a waterslide amusement park--Utah. PMID- 3088422 TI - Bat rabies--Europe. PMID- 3088423 TI - Update: influenza activity--worldwide. PMID- 3088424 TI - Importance of proper protective clothing during cleanup of a hazardous-waste site -Pennsylvania. PMID- 3088425 TI - Carbon monoxide exposures at an ice skating rink--Colorado. PMID- 3088426 TI - Behavioral risk-factor surveillance in selected states--1985. PMID- 3088427 TI - Prevalence of smoke detectors in private residences--DeKalb County, Georgia, 1985. PMID- 3088428 TI - Diagnosis and management of mycobacterial infection and disease in persons with human T-lymphotropic virus type III/lymphadenopathy-associated virus infection. PMID- 3088429 TI - Premature mortality due to malignant neoplasms--United States, 1983. PMID- 3088430 TI - Tuberculosis among migrant farm workers--Virginia. PMID- 3088431 TI - Influenza--United States, 1985-1986 season. PMID- 3088432 TI - [Isolation and characteristics of urokinase-type plasminogen activator from a culture of human embryo lung fibroblasts]. AB - Plasminogen activator from conditioned medium of human embryonal lung fibroblasts was purified by phosphocellulose P11 chromatography, followed by p aminobenzamidine-agarose chromatography. Two forms of plasminogen activators were separated by chromatography on the heparin-sepharose. The high molecular weight form (53 kDa) with specific activity 130 000 IU/mg consists of two polypeptide chains (31 kDa and 20 kDa) and exhibits strong affinity for fibrin-celite, lysine sepharose and heparin-sepharose. The low molecular weight form (32 kDa, 190 000 IU/mg) also binds to these sorbents, but more weakly, and its properties are very similar to those of low molecular weight urokinase. Activity of both forms of plasminogen activators are inhibited by monoclonal antibodies against urokinase. A number of enzymological chromatographic and immunological properties indicates, that the plasminogen activator from lung fibroblasts is of urokinase type. PMID- 3088433 TI - Solubilization and characterization of a low-affinity histamine-binding site on human blood mononuclear cells. AB - The extract of human peripheral blood lymphocytes and monocytes treated with Triton X-100, in direct- and competitive-binding studies, with 10(-6)-10(-2) M [14C]histamine contained a low-affinity binding site whose dissociation constant (Kd 1.8 X 10(-4) M) was commensurate with the concns of histamine (10(-6)-10(-3) M) that result from mast cell and basophil degranulation. Binding was enhanced by millimolar concns of divalent cations and by raising the incubation temp from 4 to 37 degrees C. It was inhibited by trypsin, EDTA, agents interacting with thiol groups, and by Triton X-100 concns greater than 0.2%. Thus a low-affinity histamine receptor that maintains its ligand-binding properties after solubilization from the cell surface was identified. PMID- 3088434 TI - [Glucose tolerance in intensive care premature infants with a birth weight below 1,500 g in the first 5 days]. AB - Plasma insulin and blood glucose values were studied in 11 stressed premature infants with birth weight below 1 500 g during the first five days after birth under increasing fluid and glucose infusion rates. The group 11 small premature neonates was subdivided; group A consisted of 6 stressed premature infants with respiratory distress syndrome (RDS stage III-IV) and/or intraventricular haemorrhage (IVH stage III-IV), and group B of 5 slightly stressed premature infants with RDS (stage I-II and/or IVH (stage I-II). During the first two days there was no difference in caloric and fluid intake in both groups. From the third day on caloric intake was much higher in group B than in group A (day 5: group A: 61.33 +/- 13.01 kcal/kg BW; group B: 78.2 +/- 18.49 kcal/kg BW). Plasma insulin values increased in both groups during the first five days after birth (group A: day 1: mean plasma insulin values 8.18 +/- 7.59 microU/ml; day 4: 27.22 +/- 32.85 microU/ml; group B: day 1: mean plasma insulin values 4.34 +/- 2.62; day 4: 11.18 +/- 8.38). Blood glucose and plasma insulin values were significantly higher in group A than in group B. CONCLUSION: Impaired glucose utilisation in severely stressed premature infants with parenteral nutrition might be due to stress induced peripheral insulin resistance. PMID- 3088435 TI - [Effectiveness of praziquantel as an antihelmintic agent in the treatment of bilharziasis]. AB - With the introduction of Praziquantel a highly effective anthelminticum against trematodes and cestodes has become available. After antischistosomal therapy with Praziquantel reduction of parasitic egg excretion occurs rapidly and lasts for at least one year under conditions with a low risk of reinfection. Patients treated with Praziquantel predominantly excrete non-viable eggs and therefore hardly contribute to a further transmission of the disease. Besides this parasitological improvement proteinuria, erythrocyturia, leukocyturia, and previously pathological lesions of the urinary tract as shown ultrasonographically more or less disappear. Praziquantel can therefore at present be considered the drug of choice in the treatment of schistosomiasis. PMID- 3088436 TI - Primary angiosarcoma of the heart. PMID- 3088437 TI - Acute acalculous cholecystitis: a limited review of the literature. PMID- 3088438 TI - The aberrant puberty hypothesis of polycystic ovarian disease: a review. PMID- 3088439 TI - Thymidine kinase activity and trifluorothymidine resistance of spontaneous and mutagen-induced L5178Y cells in RPMI 1640 medium. AB - L5178Y/TK+/- cells were treated with 3-methylcholanthrene (3MC) in order to obtain thymidine-kinase-deficient mutants (TK-/-) which were resistant to trifluorothymidine (TFTr). Clones of TK-/- cells were harvested from soft agar and adapted to growth in suspension culture. The phenotype of the TK-/- and TK+/- clones was confirmed by measuring thymidine kinase activity. These studies were undertaken with cells from 16 3MC-induced large colony clones (lambda TK-/-), 21 3MC-induced small colony clones (sigma TK-/-), and 51 spontaneous sigma TK-/- clones. Thymidine kinase activity was absent in all of the lambda TK-/- and sigma TK-/- 3MC-induced clones and also in 49 of 51 sigma TK-/- spontaneous clones. After at least 50 generations in suspension culture, TFTr was retained by 80% of the 3MC-induced lambda TK-/- cells, by 75% of the 3MC-induced sigma TK-/- cells, and by 89% of the spontaneous sigma TK-/- cells. The collective results showed that 86 of the 88 TFTr colonies examined lacked thymidine kinase activity and indicate that at least 98% of all TFTr colonies seen in the L5178Y assay are true TK-/- mutants. PMID- 3088440 TI - Induction of SOS functions by nitrogen dioxide in Escherichia coli with different DNA-repair capacities. AB - The effect of gaseous nitrogen dioxide (NO2) on cytotoxicity, induction of synthesis of UmuC and RecA proteins, and mutagenesis was studied in Escherichia coli strains with different capacities of DNA repair. Gaseous NO2 (90, 180 microliter/l) killed Escherichia coli. The recA mutant was most sensitive, the lexA mutant moderately sensitive, and the uvrA mutant and the wild-type the least sensitive. When 90 microliter/l NO2 gas was bubbled into bacterial suspensions for 30 min at a flow rate of 100 ml/min, the induction of umuC gene expression increased in the wild-type strain. NO2 also induced the recA gene expression in the wild-type strain. The synthesis of neither RecA nor UmuC proteins was induced in the recA and lexA mutants. We further investigated the NO2 mutagenesis in the cells treated with bubbling of NO2 gas. NO2 caused mutation to Trp+ of WP2. PMID- 3088441 TI - Cell-stage dependence of mutagen-induced sister-chromatid exchanges in human lymphocyte cultures. AB - The induction of sister-chromatid exchanges (SCEs) was studied in phytohemagglutinin (PHA)-stimulated human lymphocytes exposed for 1 h to mitomycin C (MMC, 3 X 10(-6) M), ethyl methanesulphonate (EMS, 2 X 10(-2) M), or 4-nitroquinoline-1-oxide (4NQO, 3 X 10(-5) M) at various cell-cycle stages of 72 h cultures. The doses of the chemical were chosen to give about 20 SCEs per cell when treated at Go. The SCE frequency increased almost linearly with MMC or EMS treatments at later times after PHA stimulation, peaking with those at 36 h (at around the first G1/S boundary in the 2 consecutive cell cycles, which was revealed by concomitant experiments), and then decreased with subsequent treatment times. Cell-cycle kinetics and the cell stages at which the cells were treated were measured by autoradiography and sister-chromatid differential staining. The data show that MMC and EMS produce larger numbers of SCEs when treated at stages closer to the beginning of S, and that the most efficient time of treatment is the G1/S boundary in the first cell cycle of the two consecutive cycles before sampling. Pulse treatment with EMS caused about 3 times larger inductions of SCEs when done at late G1/early S(G1/S boundary) in the first cell cycle compared to that at G0/early G1, whereas identical exposure to MMC at the first G1/S boundary produced only 1.5 times larger numbers of SCEs than that at G0/early G1. EMS and MMC both, however, induced 30-40% larger numbers of SCEs when treated at the G1/S boundary in the first cell cycle than when treated at the second cell cycle before sampling. On the contrary, treatment with 4NQO led to the induction of about the same numbers of SCEs even when treated at different cell-cycle stages before the second G1/S boundary. The SCE frequency in 4NQO treated cells then decreased with subsequent treatment times. PMID- 3088442 TI - Cell-cycle-dependent repair of damage in alpha and bulk DNA of monkey cells. AB - Excision repair of bulky chemical adducts in alpha DNA of confluent cultures of African green monkey cells has previously been shown to be deficient relative to that in the overall genome. We have compared the removal of adducts produced by treatment with aflatoxin B1 (AFB1) and N-acetoxy-2-acetylamino-fluorene (NA-AAF) from alpha DNA sequences in synchronized and exponentially growing cultures of monkey cells. Proficient removal of AFB1 adducts in alpha DNA was observed in exponentially growing cultures. However, as the cultures approached confluence, adduct removal from alpha DNA became deficient. Cells synchronized by subculturing confluent cultures exhibited proficient removal of adducts from both alpha and bulk DNA when treated in early G1 or late S/G2 while those cells treated in early S phase did not remove adducts from either alpha or bulk DNA. We conclude that the accessibility of chemical adducts to repair in alpha chromatin is influenced by the growth state and the cell cycle stage. PMID- 3088443 TI - Tulipa gesneriana bulb extracts activate promutagenic 7,12 dimethylbenz[a]anthracene in the salmonella/ames assay. AB - Crude extracts from Tulipa gesneriana bulbs have been tested for their ability to activate 7,12-dimethylbenz[a]anthracene (DMBA) in the Salmonella mutagenicity assay. Bacteria of strain TA98 were incubated for 30 min at 37 degrees C with the mixture of the promutagen and bulb extracts prior to plating. The frequency of his+ revertants increased in relation to both the promutagenic dose and the amount of bulb extract in the mixture, and under optimal conditions, was more than 50 times higher than the value found after the action of the promutagen alone. Addition of NADP and glucose 6-phosphate to the incubation mixture did not seem to be obligatory. PMID- 3088444 TI - Mutagenesis by ethidium bromide, proflavine and mitomycin C in the cyanobacterium Nostoc sp. AB - Ethidium bromide, proflavine, and mitomycin C were strongly lethal but weakly mutagenic to the cyanobacterium Nostoc sp. With a view to studying the mode of action of these weak mutagens, their binding to Nostoc DNA was studied. The spectral changes resulting from the binding of these mutagens to the DNA in vitro indicated that probably only electrostatic forces may be involved in the mutagen DNA binding. A similar low level of DNA binding in vivo would explain the weakly mutagenic action of the dyes observed. Since the dyes do not effectively intercalate into DNA, they may not be effective in inducing frameshift mutations but still can interfere with replication and/or transcription of the DNA. PMID- 3088445 TI - Cell cycle effects on the basal and DNA-damaging-agent-stimulated ADPRT activity in cultured mammalian cells. AB - ADP-ribosyl transferase (ADPRT) is a DNA-dependent chromatin-associated enzyme which covalently attaches ADP-ribose moieties derived from NAD+ to protein acceptors to form poly(ADP-ribose). ADPRT activity is strongly stimulated by breaks in DNA, and it is suggested that its activity is required for efficient DNA excision repair. In this paper, a cell-cycle-dependent fluctuation of basal ADPRT activity was demonstrated by measuring it in permeabilized FL cells. The cell used was subjected to arginine starvation for 48 h before being released from the block by replacement of deficient medium with complete medium and cells in different proliferating stages were traced by [3H]TdR pulse labelling and obtained at different intervals after block release. The peak basal ADPRT activity appeared 4-6 h after the appearance of the peak of DNA synthesis. After treating the cells with MNNG (10(-4) M), MMS (10(-3)-10(-4) M) and 4NQO (10(-5) M) for 90 min just after release of the block, the ADPRT activity was markedly stimulated. It was further demonstrated that the effects of MNNG/4NQO and cell cycle influence on the level of poly(ADP-ribose) synthesis appear to be additive. While concerning MMS, quite a different pattern of ADPRT stimulation in the cell cycle was demonstrated, i.e., the activity of ADPRT stimulation of 10(-3) M MMS was found to be completely dependent on the basal ADPRT activity. In the cells with the highest basal ADPRT activity 12 h after block release, the MMS-induced ADPRT stimulation could not be observed. It was suggested that more than one pathway might be present in ADPRT stimulation induced by DNA-damaging chemicals, and the cells synchronized in late G1 stage might be the most suitable for demonstrating poly(ADP-ribose) synthesis after DNA damage. PMID- 3088446 TI - Hospital institutes infant stimulation program. PMID- 3088447 TI - Identification and analysis of epimastigote surface and metabolic proteins in Trypanosoma cruzi. AB - Metabolic and surface membrane proteins of four epimastigote-stage Trypanosoma cruzi clones were analyzed by one and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. No major inter-clonal differences were observed in the metabolic protein patterns, indicating that these proteins are highly conserved. However, marked quantitative and qualitative differences were observed in surface-labeled protein patterns following both one and two dimensional electrophoretic analyses. Inter and intra-clonal differences in antigenic properties also were demonstrated by immunoprecipitation of the surface proteins with sera from animals immunized or infected with various T. cruzi stocks. Thus, a wide spectrum of both phenotypic and antigenic diversity exists in T. cruzi which may be relevant to problems of the diagnosis and immunotherapy of Chagas' disease. PMID- 3088449 TI - Shattuck lecture--the politics of medicine in Britain and the United States. PMID- 3088448 TI - Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitation. AB - We investigated the acid-base condition of arterial and mixed venous blood during cardiopulmonary resuscitation in 16 critically ill patients who had arterial and pulmonary arterial catheters in place at the time of cardiac arrest. During cardiopulmonary resuscitation, the arterial blood pH averaged 7.41, whereas the average mixed venous blood pH was 7.15 (P less than 0.001). The mean arterial partial pressure of carbon dioxide (PCO2) was 32 mm Hg, whereas the mixed venous PCO2 was 74 mm Hg (P less than 0.001). In a subgroup of 13 patients in whom blood gases were measured before, as well as during, cardiac arrest, arterial pH, PCO2, and bicarbonate were not significantly changed during arrest. However, mixed venous blood demonstrated striking decreases in pH (P less than 0.001) and increases in PCO2 (P less than 0.004). We conclude that mixed venous blood most accurately reflects the acid-base state during cardiopulmonary resuscitation, especially the rapid increase in PCO2. Arterial blood does not reflect the marked reduction in mixed venous (and therefore tissue) pH, and thus arterial blood gases may fail as appropriate guides for acid-base management in this emergency. PMID- 3088450 TI - "Blood gases": arterial or venous? PMID- 3088451 TI - Canada's health care system (1). PMID- 3088452 TI - Progressive myoclonus epilepsies: specific causes and diagnosis. PMID- 3088453 TI - Standardization and demonstration of antibody-coated Candida in urine by direct immunofluorescence test. AB - Acetone, carbontetrachloride, ethyl alcohol, mixture of ethyl alcohol and acetone, and heat were assessed for fixative property for direct immunofluorescent (IF) staining of antibody-coated Candida cells. The results indicated that ethyl alcohol was the most suitable fixative for the test. Antisera containing 16 units of Candida albicans type A agglutinin were found essential to get optimal detectable fluorescence of antibody-coated yeast cells. IF test showed cross reactivity between the yeasts of C. albicans and C. tropicalis. However, there was no cross reactivity with the conidia of A. flavus. The direct IF test could demonstrate antibody-coated yeast cells and pseudomycelia in deposits of urine in the direct smear. It correlated well with microscopy and culture studies. At times, it could demonstrate the antibody coated yeasts earlier than routine significant culture. It could also differentiate the significant from non-significant fungal isolates from urine. PMID- 3088454 TI - Equine pythiosis in Costa Rica: report of 39 cases. AB - Thirty-nine pythiosis equine cases, were studied at the Veterinary Medicine School of the National University of Costa Rica, between 1981 and 1984. Lesions were located in different parts of their anatomy: anterior and posterior extremities, abdomen, thorax, breast and mammary gland, and were characterized by their tumoral appearance with necrotic tissue in which yellow-white coral-like necrotic masses, called kunker or leeches were shown. Splendore-Hoeppli like phenomenon and eosinophilic inflammatory reaction around the hyphae, was microscopically observed. Pythium sp. (Hyphomyces destruens) was isolated in Sabouraud dextrose agar from ground kunkers. Immunodiffusion (ID) to diagnose this disease in equines, was performed with success. Immunotherapy was applied to 5 of affected horses, and three were cured. Some epizootiological aspects of the pythiosis are also discussed. PMID- 3088455 TI - GTP-binding proteins. One molecular machine can transduce diverse signals. PMID- 3088457 TI - Health promotion--education or marketing strategy? PMID- 3088456 TI - [Rupture of the lateral ankle ligament(s); surgery or not?]. PMID- 3088458 TI - Streamlining care--meeting patient needs through DRGs. PMID- 3088459 TI - [Effect of the degree of attention on the induction of epileptic seizures]. PMID- 3088460 TI - [Significance of asymmetrical spontaneous blink reflex. A controlled study in epileptics]. PMID- 3088461 TI - [Hyperammonemia in valproate therapy in children and adolescents]. AB - In order to evaluate significance and frequency of valproic acid (VPA)-induced hyperammonemia we measured venous serum ammonia, SGOT, G-GT, platelets and antiepileptic drug levels in three groups of subjects: 1.) 30 pediatric patients treated with VPA, alone or in combination 2.) 30 healthy age and sex matched subjects 3.) 30 pediatric unselected patients treated with various antiepileptic drugs except VPA. In the VPA group serum ammonia was significantly (p less than 0.01) higher than in controls and in the group 3. Patients on VPA-polytherapy had significantly higher serum ammonia values than patients on VPA-monotherapy (p less than 0.01). Hyperammonemia was found in 8 (27%) VPA-treated patients. A syndrome consisting of lethargy, stupor, hypotonia and increased seizure activity developed in 3 patients on VPA-therapy of whom two showed hyperammonemia. After discontinuing VPA this syndrome disappeared in all three cases. There was no direct correlation between VPA and ammonia levels. The etiology of hyperammonemia in VPA treated patients is not yet fully explained. It may be related to the fatal VPA induced hepatic failure reported in the literature. Some risk factors which may facilitate hepatic injury during VPA therapy (young age, co-medication, polytherapy, infectious disease, protein overload, low caloric intake) are discussed and some practical consequences are indicated. PMID- 3088463 TI - Occurrence of a nucleoprotein bound RNase in rat brain and liver. AB - An RNase activity was found to be present in rat brain and liver and was strongly bound to the nucleoprotein fractions of these tissues. It could not be solubilized by treatment with acid or by lipid solvents. The pattern of oligonucleotides produced during hydrolysis by this enzyme indicated that it was probably an endonuclease with restricted specificity. It was inhibited by zinc ions and by low pH. PMID- 3088462 TI - Serum and peritoneal dialysate thyroid hormone levels in patients on continuous ambulatory peritoneal dialysis. AB - Thyroid function tests were performed on 16 clinically euthyroid patients with end-stage renal failure undergoing regular haemodialysis or continuous ambulatory peritoneal dialysis and compared with 8 healthy subjects. The patient groups were carefully matched, especially regarding relative duration of dialysis (mean of 24 months). Total serum thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine and reverse triiodothyronine were significantly lower in both patient groups than control. The thyrothrophin response to the standard thyrotrophin-releasing hormone test was delayed and blunted. Using a novel concentration technique we measured loss of T4 in peritoneal dialysate effluent and found it to be approximately 10% of daily thyroidal T4 release. PMID- 3088464 TI - Effect of chronic valproate treatment on folate-dependent methyl biosynthesis in the rat. AB - Folate deficiency has been associated with chronic anticonvulsant therapy. Characterization of the effects of individual anticonvulsants has been undertaken. Chronic treatment of rats with sodium valproate caused a decrease in liver folate concentration with concomitant increases in brain and plasma folate concentrations. After several weeks, these trends were reversed and folate concentrations tended to normalize. Chronic valproate treatment affected the activities of folate-dependent one-carbon enzymes: Serine hydroxymethyltransferase activity in liver was increased; methylenetetrahydrofolate reductase activity in both brain and liver was decreased; and methyltetrahydrofolate:homocysteine methyltransferase activity in both brain and liver decreased initially but returned toward normal with continued treatment. Methionine adenosyltransferase activity in brain declined after several weeks of treatment but the concentration of S-adenosylmethionine in liver increased with chronic valproate treatment. These data are consistent with the hypothesis that the effects of anticonvulsants on folates are a consequence of the mechanism of action of the anticonvulsant. PMID- 3088465 TI - An improved method for the fluorometric determination of tissue catecholamines. AB - Catecholamines extracted from tissues are readily measured by fluorescence following trihydroxyindole derivatization. A complicating factor, however, has been the variably high background fluorescence levels obtained which adversely affect the precision of the assay. Employing EDTA is shown to reduce the high background fluorescence to a consistently low level, and to improve the accuracy of the trihydroxyindole method. It is suggested that high background fluorescence readings obtained by previous workers were due to metal ions extracted from tissue and carried over into the derivatization procedure. PMID- 3088466 TI - [A case of adult respiratory distress syndrome (ARDS) induced by radio chemotherapy (RAFP therapy) of brain metastasis of stomach cancer]. AB - A 77-year-old male was admitted to the hospital because of left hemiparesis secondary to multifocal cerebral metastases from adenocarcinoma of the stomach. He was treated with combination of radiotherapy and chemotherapy consisting of ACNU, Tegafur and PSK. He was in good condition, but abruptly developed severe dyspnea 40 days after administration of Tegafur and 28 days after that of ACNU. Chest X-ray at that time revealed diffuse opacity involving entire lung fields associated with marked hypoxia. The patient expired 9 days after this episode. The autopsy revealed acute interstitial pneumonitis associated with hyaline membrane formation consistent with adult respiratory distress syndrome involving entire lobes of both lungs without metastases. As to the etiology of the ARDS in this case, we concluded that the administration of Tegafur was the most likely as to the cause, although the possibility of betamethasone was not ruled out. The remaining factors were not likely as to the cause of the ARDS in this case. PMID- 3088467 TI - Effects of cupric acetate on hypothalamic gonadotropin-releasing hormone release in intact and ovariectomized rabbits. AB - The effects of intravenous injection of cupric acetate (CuAc) on release of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were explored in conscious, ovarian intact does and in ovariectomized (OVEX) does that received subcutaneous implants, either blank Silastic capsules or Silastic capsules containing crystalline estradiol-17 beta (E2). Animals were subjected to push-pull perfusion of the posterior median eminence for 6 h, and CuAc was intravenously injected (2.5 mg/kg body weight) at the end of the 2nd h of push pull perfusion. Perfusate samples were collected continuously and pooled for assay at 10-min intervals. Peripheral blood samples were obtained at 10- to 30 min intervals. Levels of GnRH in push-pull perfusate and LH, FSH, and PRL in plasma were measured by specific radioimmunoassays. In intact does (n = 4), intravenous injection of CuAc stimulated the release of hypothalamic GnRH and pituitary LH, FSH, and PRL. The initial increase and subsequent decrease in hypothalamic GnRH after CuAc injection preceded those in plasma LH, FSH, and PRL. Injection of saline into intact does (n = 4) had no effect on any of these hormone levels. In OVEX does that received blank Silastic capsules (n = 4), CuAc failed to stimulate either hypothalamic GnRH release or pituitary LH, FSH, and PRL release. In contrast, CuAc stimulated the release of all four hormones in OVEX does that received E2 containing Silastic capsules (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3088468 TI - Case for diagnosis. AIDS. PMID- 3088469 TI - Organization of the Military Health Care System. PMID- 3088470 TI - Heat illness in hot/humid environment. PMID- 3088471 TI - One short of a jury--the missing voice in an obstetrical case conference. PMID- 3088472 TI - Mezlocillin: a broad spectrum penicillin in the treatment of urinary tract infection. PMID- 3088473 TI - Cardiac arrest following protamine sulfate infusion during regional anesthesia. PMID- 3088474 TI - Medical Corps readiness for major conflict. PMID- 3088475 TI - The ethnic distribution of varicocele. PMID- 3088476 TI - New concepts in the pathophysiology and treatment of osteoradionecrosis. PMID- 3088477 TI - Military applications of digital subtraction angiography. PMID- 3088478 TI - Electrical impedance: a new technique to assess human body composition. PMID- 3088479 TI - Snuff-dipping in college students: a clinical profile. PMID- 3088480 TI - Transurethral resection of the prostate (TURP) followed by intraoperative hemorrhage incontinence. PMID- 3088481 TI - [Extensive intestinal resection for infarct]. PMID- 3088483 TI - [Intraluminal diverticulum of the duodenum]. PMID- 3088482 TI - [Experimental evaluation of CO2 lasers in general surgery]. PMID- 3088484 TI - [Up-date on enteral nutrition: percutaneous gastrostomy and minimal jejunostomy]. PMID- 3088485 TI - [Effects of the CO2 laser in the surgery of Vater's papilla. Experimental study in the rabbit using microsurgical technics]. PMID- 3088486 TI - [Acute occlusive syndromes of non-neoplastic origin]. PMID- 3088487 TI - [Thyroid nodular pathology in old age]. PMID- 3088488 TI - [Cerebral vasospasm caused by subarachnoid hemorrhage]. AB - Vasospasm is one of the most frequent complications of subarachnoid hemorrhage (SAH) and causes high mortality rates and serious neurologic deficits, resulting in invalidity. Diagnosis is based on precise clinical criteria (onset between the 3rd and the 8th day after the SAH) and is confirmed by angiographic examination. The etiology certainly involves many factors, though the identification of the primary cause (conductive to morpho-structural alterations of the artery walls) seems to be troublesome. Experimental evidence indicates that the basis of the reactions which cause the onset of the vasospasm lies in the blood which pools in the subarachnoid zone. The authors summarize the main pathogenetic theories, especially as far as the initial biochemical sequence is concerned. Among the numerous classes of substances involved in the genesis of vasospasms, a relevant role is played by oxyhaemoglobin, free radicals, lipidic peroxides and by the metabolites of arachidonic acid. The main purpose of vasospasm treatment is the possibility to eliminate and prevent ischemic complications. Early surgical exclusion of the aneurysm causing the bleeding allows for the removal of peri aneurysmatic blood clots. Pharmacological treatment employs numerous classes of substances: among these calcium antagonists presently appear to give satisfactory results. PMID- 3088489 TI - [Cerebral vasospasm. Clinical and experimental aspects]. AB - A large number of experimental data suggest a possible biochemical hypothesis for the trigger stimulus of cerebral vasospasm after subarachnoid hemorrhage (SAH). Among several classes of possible spasmogens, arachidonic acid metabolites may play a primary role. Authors have measured with radioimmunoassay technique (R.I.A.) the levels of four arachidonate metabolites (PGD2, TxB2, 6-keto-PGF1 alpha and i-LTC4) in lumbar and cisternal cerebrospinal fluid (CSF) of patients admitted with diagnosis of aneurysmal SAH. In all cases a significant activation of arachidonate metabolism is found, if compared to control cases. Patients with demonstrated vasospasm have significantly higher CSF levels of PGD2 and i-LTC4. Cisternal CSF levels of four metabolites are significantly higher than lumbar CSF levels. This suggests the correlation between subarachnoidal clot extension and the risk for vasospasm. Authors also present an experimental animal model of SAH, which is reliable from a pathological standpoint. This model could be therefore used in the study of neurochemical and neuropharmacological aspects of SAH. PMID- 3088490 TI - [Anesthesiological considerations in surgery of cerebral aneurysms]. AB - A well integrated and coordinated team between Neurosurgeon and Anesthetist is necessary to achieved the best results in aneurysm surgery. Drugs-induced hypotension, cerebral metabolic depressant drugs (such as thiopentone), new anaesthetic drugs, hypocapnia are the anaesthetic techniques of choice in intracranial aneurysm surgery. PMID- 3088491 TI - [Determination of lymphocyte subpopulations in multiple myeloma and monoclonal gammopathies of undetermined significance]. AB - By means of monoclonal antibodies, the lymphocyte subpopulation in 12 patients affected by multiple myeloma, 3 by Waldenstrom's macroglobulinemia, 7 by M.G.U.S. and 8 patients affected by accompanying monoclonal gammopathy have been determined. The group of patients affected by multiple myeloma or Waldenstrom's macroglobulinemia presented, against control, a significant reduction in the OK T3+ and OK T4+ cell percentage, with a remarkable reduction of the OK T4+/OK T8+ ratio. The OK T8+ cell average, if considered as an absolute value, was not modified in comparison to normal value, while the absolute number of OK T4+ cells was substantially reduced. No significant modifications have been ascertained in the percentage of SIg+ cells. The patients affected by M.G.U.S. did not present significant difference against controls, with regard to the lymphocyte number and the percentage of OK T3+ and OK T4+ cells. On the contrary, a significant increase of the percentage and absolute number of OK T8+ cells was observed. Also in these cases, a significant reduction of the OK T4+/OK T8+ ratio was observed. Finally, the patients affected by accompanying monoclonal gammopathy presented a significant reduction of OK T3+ and OK T8+ cells, with an increase of the percentage of OK T4+ cells and of the OK T4+/OK T8+ ratio. PMID- 3088492 TI - [Role of total parenteral nutrition (TPN) in the treatment of pseudomembranous colitis in surgical patients. Our experience]. AB - The authors describe their experience using TPN (total parenteral nutrition) associated with specific drugs in the treatment of antibiotic-associated pseudomembranous colitis in surgical patients. They discuss the benefits and the possible complications of the above mentioned treatment. Three different cases observed during a three year period are reported; one of these is carefully analysed in order to better explain the methods and procedures used during TPN. PMID- 3088493 TI - [In vitro sensitivity of 39 strains of Pseudomonas aeruginosa isolated from urine culture of hospitalized patients]. AB - Research was conducted in 39 cases of urinary infections caused by Pseudomonas Aeruginosa in patients in various hospital wards. The aim was to assess the onset of such opportunistic infections in the hospital environment as reported earlier by other authors. A comparison was then made between the most commonly used antibacterial drugs used to combat such infections assessing their percentage efficacy on the basis of the germs' resistance to the drug. PMID- 3088494 TI - Home care of the child receiving nutritional support. A global approach. PMID- 3088495 TI - Peripheral parenteral nutrition. PMID- 3088496 TI - The supplementary motor area modulates perturbation-evoked discharges of neurones in the precentral motor cortex. AB - The hypothesis was tested that the supplementary motor cortex (SMA) may influence the responsiveness of area 4 neurones to kinesthetic stimuli. In the awake monkey, responses to arm displacements were recorded with and without conditioning intracortical stimulation of the SMA. In 14 of 26 tested area 4 neurones, there was an increase of the response latency and/or a decrease of the response magnitude when the peripheral stimulus was conditioned by SMA stimulation. Field potentials evoked by the displacements were reduced in 3 out of 7 recordings. These findings suggest that the SMA exerts subtle inhibitory effects on the motor cortex or its inputs. PMID- 3088497 TI - Coexpression of human growth hormone-releasing factor 1-37-like and alpha melanotropin-like immunoreactivities in neurones of the rat lateral dorsal hypothalamus. AB - Antibodies recognizing the 29-37 sequence of the human somatocrinin specifically stain a large population of interneurones located in the lateral dorsal hypothalamus. Staining comparisons revealed that these perikarya also contain alpha-MSH-like immunoreactivity. The neurones exhibiting human GRF1-37-like immunoreactivity correspond to the system previously shown to present alpha-MSH like and rat CRF-like immunoreactivities. PMID- 3088498 TI - Presence of glycoproteins containing the polylactosamine structure in brain and liver of GM1 gangliosidosis patients. Comparative study between clinical types I and II, using endo-beta-galactosidase enzyme. AB - The material derived from defective degradation of glycoproteins, which accumulates in brain and liver of a patient with GM1 gangliosidosis type I, was investigated, and the structure of the main storage compounds determined. For comparison, brain and liver of a patient with GM1 gangliosidosis type II were also analyzed. Analysis of the glycopeptides obtained after pronase digestion of the defatted residue indicates the storage of glycoprotein-like material in type I, but not in type II. Treatment with endo-beta-galactosidase showed that the stored material contained N-acetyllactosamine repeating units. Two major oligosaccharides, OS I and OS II, were isolated after the enzyme treatment, whose structures are: GlcNAc beta 1----3 Gal (OS I) and Gal beta l----4GlcNAc beta 1--- 3 Gal (OS II). Treatment with exo-beta-galactosidase transformed the trisaccharide OS II into the disaccharide OS I, indicating that the deficiency of beta-galactosidase in GM1 gangliosidosis type I, but not in type II, also affects glycoprotein catabolism, leading to the accumulation of glycopeptides containing terminal beta-galactosyl residues and N-acetyllactosamine repeating units. These results indicate the severe impairment in the catabolism of glycoconjugates with beta-linked galactose in type I, although this impairment is not as pronounced in type II. PMID- 3088499 TI - Nutrition classics. Archives of Disease in Childhood. Volume VIII, 1933. A nutritional disease of childhood associated with a maize diet. By Cicely D. Williams. PMID- 3088500 TI - Arachidonate retention in essential fatty acid deficiency. PMID- 3088501 TI - Are i.v. in-line filters worth the price? PMID- 3088502 TI - Assessment of nutritional status. PMID- 3088503 TI - New legislation tightens PPS. PMID- 3088504 TI - [Molecular biology in tumor diagnosis. New ways for the detection, classification and staging of malignant lymphomas]. PMID- 3088506 TI - Comparison of oral ftorafur and intravenous 5-fluorouracil in patients with advanced cancer of the stomach, colon or rectum. AB - In this prospective randomized study the effect of oral Ftorafur was compared with that of intravenous 5-fluorouracil in patients with advanced adenocarcinoma of the stomach, colon or rectum. Forty-five patients were evaluable. The overall response rates were 26.9% in the 5-fluorouracil group, 26.7% in the Ftorafur group. The median duration of response was 6 months in both groups. Survival in the 5-fluorouracil group was slightly better than in the Ftorafur group, but the difference was not statistically significant. The myelosuppressive effect of 5 fluorouracil was significantly stronger than that of Ftorafur. Gastrointestinal side effects were more pronounced in the Ftorafur group, but the difference was not statistically significant. PMID- 3088505 TI - [Rearrangements of immunoglobulin and T-cell-antigen receptor genes as diagnostic markers in lymphatic neoplasms]. AB - During recent years cloning of the genes encoding the immunoglobulin (Ig) and T cell (TCR) antigen receptor has made it possible to analyze clonal expansions of B- or T-cells at the molecular level. We here describe the usefulness of the Ig- and TCR-gene rearrangements in selected cases of malignant lymphoma. In contrast to all other cases investigated, one non-Hodgkin's lymphoma (NHL) exhibited the infrequent phenomenon of oligoclonality, i.e. three distinct B-cell clones were discerned by Southern blot analysis. Detection of clonal TCR- and Ig-gene rearrangements unequivocally documented bone marrow involvement in four of eight NHL-patients, where conventional histologic and cytologic examination remained inconclusive. As expected, analysis of bone marrow DNA revealed clonal Ig-gene rearrangements in three cases with clear histologic evidence of bone marrow infiltrations by the NHL. In one case of a patient with acute mixed lymphoid myeloid lineage leukemia a previously identified clonal Ig-gene rearrangement vanished after successful chemotherapy. Analysis of Ig- and TCR-gene rearrangements promises to be a very useful diagnostic tool in selected cases of lymphoid neoplasia. PMID- 3088508 TI - "Good morning: this is Mr. Cataract, and this is Mrs. Glaucoma". PMID- 3088507 TI - Quantitative changes in surface immunoglobulin expression in WEHI-231 lymphoma cells in relation to their proliferative rate. AB - Quantitative changes in surface immunoglobulin expression were studied in relation to the proliferative behavior of WEHI-231 cells. They undergo morphologic, biochemical and immunologic changes during the course of growth in culture. Changes in cell size and morphology, as well as DNA and RNA synthesis, resemble features of normal lymphocyte transformation. During log phase growth there was a more than 30-fold increase in cell number over a 4-day period in the absence of medium change. The average log phase population doubling time was 20 h. Plateau phase was achieved on day 5, and maintained through day 7. Image analysis studies of cytocentrifuged cells demonstrated increases in cell, and nuclear area that became apparent within 2 h of transplantation. Tritiated thymidine incorporation rose rapidly peaking on days 2 and 3, and then fell progressively to 35% of peak values on day 4. Tritiated uridine incorporation into RNA showed similar changes. Changes in S fraction, as determined by flow cytometry, paralleled the changes in tritiated thymidine incorporation. Cell surface IgM and kappa light-chain immunoglobulin were also measured by flow cytometry. Mean values were low initially, rose slowly, increased rapidly to peak values on days 3 and 4, and then fell progressively. Peak surface immunoglobulin levels were observed during the transition of cells from log phase to plateau phase growth, and coincided with the appearance of large numbers of small cells with low rates of DNA and RNA synthesis. Thus, maximum expression of surface Ig was associated with growth retardation, and not with early rapid growth phase. The maximal expression of surface immunoglobulin in small slowly proliferating cells may have important implications for immunotherapy with monoclonal antibodies alone. PMID- 3088509 TI - Evaluating the applications of the spatially adaptive program (SAPRO) in clinical perimetry: Part II. PMID- 3088510 TI - [TSH and prolactin studies with TRH-loading in juvenile Basedow's disease]. PMID- 3088511 TI - [Treatment of extra-puerperal galactorrhea with the MAO-B inhibitor selegiline]. PMID- 3088512 TI - Teaching pediatric otolaryngology to pediatricians and other nonotolaryngologists. PMID- 3088513 TI - Neuromas of the skull base. AB - Ten skull-base neuromas treated at the Otology Group P.C. are presented. Each case is reported in detail. The method by which preoperative diagnosis was made is reviewed. Specific attention is paid to distinguishing these tumors from chemodectomas. Presenting signs and symptoms are enumerated. Operative- especially postoperative--management is discussed in detail. PMID- 3088514 TI - A modified technique for tubeless tracheostomy. AB - The dog is an animal widely used in experiments, and tracheostomy is frequently necessary when laryngeal experiments are carried out. Unfortunately, dogs generally do not tolerate tracheostomy well because the inserted cannula easily becomes displaced or blocked. This article presents a new surgical technique aimed at providing a long-term, dependable, and safe airway. It is based on previously established, clinically tested principles to avoid local tracheal complications. No essential tissue is removed or irreparably damaged and the procedure is reversible. Flexibility in management of the resultant stoma is possible, allowing either maintenance of maximal patency or gradual closure. Twenty-one animals were studied for 3- and 6-month periods, and there was no morbidity because of airway obstruction. This technique can reduce loss of valuable experimental animals caused by airway complications. It may also have application in human beings. PMID- 3088515 TI - ABR screening of high-risk infants: effects of ambient noise in the neonatal nursery. AB - This investigation examined ABR waveforms obtained at five signal intensities (20, 30, 40, 60, and 80 dB nHL) for adults and at three signal intensities (20, 40, and 80 dB nHL) for infants. ABR recordings were obtained in a quiet condition and repeated for three different intensity levels (40, 50, and 60 dBA) of background noise characteristic of a neonatal intensive care unit. The subjects were ten adults and ten infants whose ABRs were judged normal when measured at 20 dB nHL in the quiet condition. Results indicated that high levels of ambient noise (up to 60 dBA) did not influence either absolute wave V or interwave latencies measured for stimulus intensities of 60 and 80 dB nHL. ABR waveforms obtained at stimulus intensities often used for screening (i.e., 20, 30 or 40 dB nHL), however, were substantially altered for some subjects as a function of increasing levels of ambient noise. This observation was most apparent for the infant population and has important implications for the design of infant ABR screening programs. PMID- 3088516 TI - A review of twenty congenital cholesteatomas of the middle ear in children. AB - Cholesteatomas, arising within the middle ear space behind an intact tympanic membrane, have been detected more frequently in recent years. This article reviews 19 children (with a mean age of 4.3 years) who underwent surgery over a 7 year period for removal of cholesteatomas from behind intact tympanic membranes. Most of these children were referred by pediatricians who had detected an asymptomatic whitish middle ear mass. Many had histories of treatment for otitis media. Patients with similar histories were excluded from the series if there had been a prior perforation, myringotomy, or otologic surgery. In the series, one fourth of the children had associated congenital malformations, and there were 3 times as many boys as girls. In two thirds of the cases, the cholesteatoma was manifested as an anterior-superior middle ear mass that seemed to arise from the processus cochleariformis, undersurface of malleus area. Many could be removed via an extended anterior tympanotomy operative approach. The results of surgery are reviewed. The possible origins of these localized cholesteatomas are considered. Are they congenital defects that arise from misplaced keratinizing epithelium? Do they arise from mesenchymal cells whose differentiation is stimulated by inflammatory changes within the middle ear? PMID- 3088518 TI - Surgical correction of congenital atresia of the ear. AB - Severe congenital atresia of the ear often requires--or indicates the need for- reconstructive surgery. We have developed a new technique for reconstruction of the external auditory canal. What follows is description of this technique and the results of its implementation. PMID- 3088517 TI - ABR results in patients with posterior fossa tumors and normal pure-tone hearing. AB - Sixteen patients with confirmed mass lesions of the posterior fossa and normal hearing sensitivity for pure tones were studied. Patients' main symptoms, auditory brain-stem response (ABR), and lesion size were analyzed. All patients manifested neurologic and/or otoneurologic symptoms or complained of hearing difficulty disproportionate to their pure-tone findings. Interestingly, the patients in this select group were younger (mean = 34 years) than the typical patient with a posterior fossa tumor. ABR results were abnormal in 15 of the patients, although several indices--including absolute and interwave latencies, interaural latency difference, and wave presence/absence--were employed to achieve this sensitivity. Lesion size varied considerably and failed to correlate with ABR or pure-tone results. PMID- 3088519 TI - Pediatric videonasoendoscopy for speech and voice evaluation. AB - Many otolaryngologists and speech clinicians have found videofiberoptic evaluations to be invaluable for assessment of velopharyngeal and laryngeal function in adults. However, many professionals question the feasibility of routine use of these procedures in the pediatric population. This article describes a method for successful completion of videonasoendoscopic speech and voice evaluations of children as young as 3 years of age. The importance of the ENT/speech team is emphasized in both the collection and interpretation of data. In addition, contributions of videonasoendoscopic observations to diagnosis, medical treatment, and therapy for speech and voice disorders are discussed. PMID- 3088520 TI - Maxillary, mandibular, and hyoid advancement: an alternative to tracheostomy in obstructive sleep apnea syndrome. AB - Nine patients with severe obstructive sleep apnea syndrome (OSAS)--for whom several therapeutic approaches, including palatopharyngoplasty, had failed--were treated with a combined maxillary, mandibular, and hyoid advancement. Objective evaluation--performed before and 4 to 18 months after surgery, using nocturnal polysomography--indicated that the OSAS had improved or had disappeared. This surgical approach is beneficial for specific cases of OSAS, which can be identified by mandatory presurgical tests. PMID- 3088521 TI - Inferior sagittal osteotomy of the mandible with hyoid myotomy-suspension: a new procedure for obstructive sleep apnea. AB - Five patients were treated by inferior sagittal osteotomy and hyoid myotomy suspension. In three of the patients, palatopharyngoplasty had previously failed. One of the patients was noted to have mandibular deficiency; the others had normal skeletal development. Nocturnal polysomnograms were performed preoperatively and postoperatively. All patients showed significant improvement. PMID- 3088522 TI - Operations on the saccus endolymphaticus and vestibular nerve: have they fulfilled their promise? AB - The rationale for operations on the saccus and vestibular nerve in patients incapacitated by Meniere's disease as a replacement for total labyrinthectomy, has been the expectancy that less radical procedures will protect these patients from total auditory incapacity. Aware of postoperative hearing losses in some patients after 3 years, we have studied the results in 21 Shambaugh saccus decompression (SD) and 29 middle fossa vestibular nerve section (VNS) operations, in order to assess the claims made for these procedures. We found that while control of vertigo was similar to that reported elsewhere, worse hearing (AAOO criteria) developed in many cases. With SD this increased from 14% at 1 year to 58% at 10 years, and with VNS it increased from 17% at 1 year to 48% at 10 years, when the worse preoperative audiogram was used. Only 17% of SD and 11% VNS ears with serviceable best preoperative hearing had retained this at 10 years. Nineteen percent developed audiometric evidence of contralateral disease during the first 10 postoperative years. It is concluded that although, regrettably, neither of these surgical therapies appears to have the capability of preventing the progress of hearing loss, the reality of bilateral disease justifies the continued use of SD or VNS by adequately trained surgeons. PMID- 3088523 TI - Value of radiation therapy in addition to surgery for cancer of the head and neck. AB - This historically controlled study evaluates radiation therapy in 119 patients- with squamous cell carcinomas of the head and neck--who underwent surgery alone (SA) or surgery plus radiation (S + R). The primary tumor control and nodal control, in patients with negative surgical margins who had surgery alone (SA), were 63% in the oral cavity, 60% in the oropharynx, and 67% in the hypopharynx. The same rates for S + R group and negative surgical margins were 100%, 73%, and 100%. Combining the patients with negative and positive surgical margins, control of the tumor and nodal control were the same in the oral cavity for both treatment groups (41% for SA and 44% for S + R) and increased with the addition of radiation in the oropharynx (30% for SA to 65% for S + R) and hypopharynx (33% for SA to 86% for S + R), in spite of higher percentages of T3 and T4 tumor and positive lymph nodes in the S + R group. The lower control rate in patients who had surgery alone could be due (in part) to inadequate surgery at the primary site (42% local excision) and lack of neck dissection (35% for SA vs. 77% for S + R). Postoperative radiation therapy to the primary site and neck is shown to effectively reduce local recurrence in patients with oral cavity and oropharynx cancer, regardless of surgical margins. PMID- 3088524 TI - The violated neck: cervical node biopsy prior to definitive treatment. AB - The intent of this study was to determine whether open neck biopsy for patients with squamous cell carcinoma metastatic to the neck influenced the biologic course of the disease or the response to treatment. One hundred ninety-two patients, treated over a 10-year period at M.D. Anderson Hospital and Tumor Institute, were reviewed; 102 of the 139 patients, whose primary site of disease was identified prior to definitive treatment, were matched with a control group of 204 patients. The results showed no significant difference in wound complications, neck recurrence, distant metastases, and 5-year survival. Also, time interval from the biopsy to subsequent treatment and the type of node biopsy did not appear to have any significant detrimental effect. On the basis of these findings, we conclude that, although it is important to refrain from proceeding with an open biopsy until a complete head and neck evaluation has been done, violation of the neck does not signify a poorer prognosis--provided adequate treatment is subsequently given. PMID- 3088525 TI - Long-term experience with biocompatible ossicular implants. AB - The senior author's 8-year personal experience with biocompatible ossicular implants is reviewed. Four hundred sixty-one consecutive operations, in which high-density polyethylene sponge ossicular replacement prostheses were used, are grouped according to the Bellucci classification of chronic otitis media. The prostheses used were the drum-to-footplate prosthesis (TORP, total) and the drum to-stapes prosthesis (PORP, partial). Each group's short- and long-term hearing results are compared. Prosthesis extrusion and persistent or recurrent conductive hearing loss are the most common causes of operation failure. Failures within each group are analyzed, and techniques to prevent these complications are outlined. PMID- 3088526 TI - Aberrant internal carotid artery: classic findings on computed tomography. AB - An aberrant internal carotid artery passing through the middle ear is rare and may be misdiagnosed. Surgical intervention can lead to massive bleeding, possible hemiparesis, or both, as demonstrated by the following cases. The purpose of this article is to alert the otolaryngologist and the radiologist to the condition and to subtle computed tomographic features of an aberrant internal carotid artery. Recognition of these features should spare both surgeon and patient the consequences of ill-advised surgery. PMID- 3088528 TI - Intensification and habituation of experimental motion sickness in squirrel monkeys by repeated horizontal rotation. AB - The aim of this research was to quantify the development of habituation or intensification of experimental motion sickness induced in Bolivian squirrel monkeys by repeated exposures to horizontal rotation. Incidence, frequency, and latency of vomiting responses were recorded from monkeys rotated daily in a transparent testing chamber at 30 rpm for periods of 1 or 2 hours. Data showed that more than half of the subjects revealed habituation in terms of increased latencies for vomiting. Some showed a tendency to vomit increasingly earlier with multiple daily exposures to rotation. The development of habituation and intensification was evident as early as the second day of rotation. The number of emetic episodes per day decreased as a consequence of repeated rotation, but intensification of vomiting frequency did not occur beyond the fifth day. PMID- 3088527 TI - Cat-scratch disease. AB - Cat-scratch disease has been reported with increasing frequency since its initial description in 1931. It is now recognized as being so prevalent that it probably represents the most common cause of unilateral lymphadenopathy in children, once nonspecific viral diseases and cutaneous infections have been excluded. The cardinal feature of the disease is a subacute regional granulomatous lymphadenitis. Because of its relatively mild natural course, most cases are treated on an outpatient basis. Forty-four children, representing the more seriously ill portion of the disease spectrum, were treated at Texas Children's Hospital from 1972 to 1984 and constitute the data base for this article. Most patients were symptomatic for nearly 1 month prior to admission, typically complaining of low-grade fever and regional lymphadenopathy. The two most common sites of lymph node involvement were the axilla (54%) and the neck (46%). Although there is, at this time, no specifically recommended treatment, 80% of patients received antibiotics and 70% underwent a surgical procedure--usually total nodal excision. Nodal excision was followed by rapid resolution of symptoms. Because cat-scratch disease is benign, surgery should be reserved for severe cases with signs of significant suppuration. Generally, symptomatic relief can be afforded by warm soaks and analgesics and recovery over the course of several weeks is uneventful. PMID- 3088529 TI - Malignant degeneration of an epidermoid of the temporal bone. AB - An epidermoid (congenital cholesteatoma) in the CPA is similar to an acoustic neuroma but can often be differentiated by a normal internal auditory canal and increased radiolucent areas on CT scan. The presence of an atypical lesion on the CPA is suggestive of a metastatic lesion and warrants careful evaluation for an occult primary lesion prior to resection. Despite increasingly sophisticated techniques for removal of these lesions, the possibility of complete resection is slim and the ultimate prognosis is poor. PMID- 3088530 TI - Parapharyngeal abscess: an unusual complication of aural cholesteatoma. PMID- 3088532 TI - Acute necrotizing otitis media. PMID- 3088531 TI - Malignant schwannoma of the cervical vagus nerve in a patient with neurofibromatosis (von Recklinghausen's disease). AB - A patient with malignant schwannoma arising from the cervical vagus nerve has been described. Treatment consisted of wide en bloc resection of the tumor and adjacent carotid artery. A subclavian-middle cerebral arterial bypass procedure, using a saphenous vein graft, was performed. A course of postoperative radiotherapy was administered. The patient remains without evidence of disease 11 months following therapy. PMID- 3088533 TI - An instruction method for placing the prosthesis around the incus in stapes surgery. PMID- 3088534 TI - The "Silver" osteotome--return of the original design. PMID- 3088535 TI - Chemical irritant algesia assessed using the human blister base. AB - The chemical irritants o-chlorobenzylidene malononitrile (CS), n nonanoylvanillylamine (VAN) and dibenzoxazepine (CR) and several of its derivatives have been assayed using the human blister base. The relative potencies found by this method, CR greater than VAN greater than CS, conflicted with those found in non-human test systems but the rank order of potency of CS and CR reflected that reported in tests on the human eye and tongue. Data derived from humans thus appear to be of importance when assessing irritant potency. Interactions between CS, CR, VAN, capsaicin and bradykinin were investigated to discover any common pathways of irritant activity. Self-desensitization developed on repeated application of all agents to the blister base and selective cross desensitization also occurred. PMID- 3088536 TI - The alternative pathway of complement in sheep during the course of infection with Trypanosoma congolense and after Berenil treatment. AB - Experimental T. congolense infections in sheep resulted in a striking decrease in parameters of the alternative complement pathway (ACP), ie. factor B, C3 and haemolytic complement activity (HA) initiated via the ACP. The levels of factor B, C3 and HA declined before, during and after the first wave of parasitemia which reached a peak at day 8. Levels of 20 to 25% of normal values (factor B) and 20% (C3, HA) persisted throughout the course of the infection. After Berenil treatment, when no parasites were detected in blood, their serum levels remained low. The returned to normal values about 8 (factor B) to 20 days (C3, HA) after trypanocidal treatment. Serum concentrations of factor B were significantly elevated in some, but not all sheep 6 days after infection with T. congolense. The sheep were tested for their potential state of immuno-modulation by immunization with Brucella abortus 4 days after trypanocidal treatment. In contrast to other sheep, the sheep which had shown early elevated serum factor B levels were found to express immune enhancement. It is suggested that there might be a positive correlation between the degree of enhanced serum levels of factor B at the early stage of infection and enhanced immune responsiveness. PMID- 3088537 TI - The role of pulmonary cellular reactions in the resistance of vaccinated mice to Schistosoma mansoni. AB - A histopathological and ultrastructural study was made of schistosomula and associated inflammatory reactions in the lungs of normal mice, and mice previously vaccinated with irradiated cercariae. In normal mice at day 7 post infection all schistosomula were located in blood vessels. From day 11 onwards an increasing proportion of schistosomula were intra-alveolar (80% from day 20). No cellular reactions were evident around intravascular parasites in normal mice but at later sampling times large compact foci were associated with alveolar parasites. Initial reactions, probably in response to non-specific tissue damage, were approximately 50% polymorphonuclear, and 50% mononuclear. Mononuclear cells predominated at later times. In spite of inflammation, no damage to the schistosomula was observed. There was no evidence for re-entry of schistosomula into blood vessels, and it was assumed entry into alveoli occurred accidentally as parasites attempted to traverse pulmonary blood vessels. The pattern of localization of schistosomula in vaccinated mice was similar to that in normal mice, the proportion in alveoli increasing with time (64% from day 20). The most significant difference was that intravascular schistosomula attracted foci of host leucocytes which were always 85% or more mononuclear, containing both lymphocytes and macrophages. The infiltrating cells enlarged the intersititium, separating the vascular endothelium from the alveolar epithelium. Fibrous protein was also deposited in the interstitial region. In some instances the complete blood-air barrier was destroyed by the infiltrates. Unusual paracrystalline inclusions were observed in alveolar macrophages and giant cells. The differences in cellular responses in vaccinated and normal mice suggest that challenge schistosomula stimulated an anamnestic immune response. The resulting inflammation, by impeding movement through the vasculature, terminated migration in the lungs, and accounted for the observed resistance to reinfection. The reactions in vaccinated mice have many of the features of a delayed hypersensitivity response implying that lung phase resistance in vaccinated mice may be T-cell rather than antibody-mediated. PMID- 3088538 TI - Differential diagnosis of intra- and perivesical abnormalities using bladder air/CO2 contrast sonography. AB - Sonographic air/CO2 contrast studies of the urinary bladder allow identification of abnormal peri- and intravesical low-echogenic structures and can differentiate between those that communicate with the bladder (refluxing ureters, bladder diverticula, patent urachus) from others that do not communicate (cysts of ovarian/enteric origin, urachus cyst). Ureteroceles with a refluxing/obstructed ureter can be more clearly delineated using gas contrast than with plain ultrasound. In a group of 217 children examined by bladder contrast sonography, 19 showed pathological peri- and intravesical findings, 17 of which were definitely evaluated by bladder contrast sonography. On the other hand, only 10 abnormalities of these 19 could be detected, and in not more than 8 was the final diagnosis made by plain sonography alone. PMID- 3088540 TI - Geriatric nursing: today's realities, tomorrow's possibilities. PMID- 3088541 TI - Community-based initiatives in long-term care. PMID- 3088539 TI - [Analysis of drug sensitivity of microorganisms isolated from children treated at the Institute of Mother and Child]. PMID- 3088542 TI - Institutional long-term care: nursing role and responsibilities. PMID- 3088543 TI - In vitro transcription of bacteriophage phi 29 DNA. Correlation between in vitro and in vivo promoters. AB - The phi 29 DNA in vitro transcription initiation sites have been accurately mapped by S1 protection experiments. The results obtained indicated that the B. subtilis RNA polymerase containing the sigma 43 subunit basically recognized the same set of phi 29 promoters in vitro as those used in vivo. In addition, the sequence of the phi 29 early A2a promoter used both in vitro and in vivo has been determined as well as the precise nucleotide where initiation of transcription from the C2 promoter occurs in vitro. PMID- 3088544 TI - Nuclear factors bind to regulatory regions of the mouse kappa immunoglobulin gene. AB - At least two regions of the mouse kappa immunoglobulin gene are necessary for appropriate transcription. One is located within the J-C intron; another is located 5' of the transcription start site in all variable region gene segments and contains a highly conserved octanucleotide sequence, ATTTGCAT. Trans-acting nuclear factors have been thought to interact with these regions on the basis of studies with transient transfection of modified immunoglobulin genes into lymphoid and fibroblast cell lines. Using a sensitive gel electrophoresis DNA binding assay, we have found nuclear factors that bind to these two regulatory regions of the kappa gene. Two patterns of specific binding of nuclear factors to DNA sequences containing the J-C intron enhancer were observed. One pattern was seen in cell lines which do not express immunoglobulin, while a different pattern was observed in cell lines which actively transcribe light chain genes. We also find factors which bind to the octanucleotide containing 5' sequence which are distinct from those which bind the J-C enhancer region. PMID- 3088546 TI - Specificity of ionizing radiation-induced mutagenesis in the lac region of single stranded phage M13 mp10 DNA. AB - M13 mp10 single-stranded phage DNA was irradiated with 60 Co gamma-rays, and transfected into Escherichia coli. One hundred and sixteen mutant clones having lesions in the lac insert were selected, and mutational sites were examined by DNA sequence analysis. Fourteen out of the 15 nucleotide changes thus detected were base substitutions, and the rest was a base addition. Transitions and transversions were almost equal in number. Mutational events were observed at cytosine residues more frequently than at other residues, and the predominant base change was a C ---- T transition. Possible roles in gamma-ray-induced mutagenesis played by the misincorporation of dAMP owing to radiolytic derivatives of cytosine residues and/or formation of apurinic/apyrimidinic sites are discussed. PMID- 3088545 TI - Replication of phage phi 29 DNA in vitro: role of the viral protein p6 in initiation and elongation. AB - The phi 29 protein p6 stimulates the formation of the protein p3-dAMP initiation complex when added to a minimal system containing the terminal protein p3, the phi 29 DNA polymerase p2 and phi 29 DNA-protein p3 complex, by decreasing about 5 fold the Km value for dATP. In addition, protein p6 stimulates elongation of the p3-dAMP initiation complex. Whereas the effect of protein p6 on initiation is similar with protein p3-containing fragments from the right or left phi 29 DNA ends, the stimulation of elongation is higher with the right than with the left phi 29 DNA terminal fragment, suggesting DNA sequence specificity. The stimulation by protein p6 of the initiation and elongation steps of phi 29 DNA replication does not require the presence of the parental protein p3 at the phi 29 DNA ends. No effect of protein p6 was obtained on the elongation of the template-primer poly(dT)-(dA) 12-18 by the phi 29 DNA polymerase. PMID- 3088547 TI - Therapy for the elderly. She's the cat's whiskers. PMID- 3088549 TI - Time course of radiometric detection of positive blood cultures in childhood. AB - We have determined the time course of radiometric detection of microbial growth in 2348 positive blood culture specimens obtained at Wyler Children's Hospital during a 5-year interval. Overall 72 and 88% of isolates were detected within 48 and 72 hours after sampling, respectively. For pathogenic organisms aerobic detection was generally more rapid and more inclusive than anaerobic detection. At 48 hours of incubation the detection of six potential pathogens (Salmonella sp., Haemophilus influenzae, Group D streptococci, Neisseria meningitidis, coagulase-negative staphylococci, Candida sp.) was significantly delayed compared with detection of other pathogenic organisms recovered from blood. At 72 hours of incubation the detection rates remained less than 95% for H. influenzae, Staphylococcus aureus, Klebsiella sp., coagulase-negative staphylococci, Group D streptococci and Candida sp. These data should assist clinical decisions regarding duration of antibiotic therapy for the presumptive diagnosis of bacteremia in children. PMID- 3088548 TI - Safety and efficacy of once daily ceftriaxone for the treatment of bacterial meningitis. AB - Fifty-seven patients with bacterial meningitis were treated with once daily ceftriaxone. After an initial loading dose of 100 mg/kg, the patients received 80 mg/kg as a single daily dose. Etiologic agents included: Haemophilus influenzae type b, 37 (11 beta-lactamase-positive); Neisseria meningitidis, 11; Streptococcus pneumoniae, 6; Streptococcus pyogenes, 1; Haemophilus influenzae type f, 1; and Group B Streptococcus, 1. All patients showed clinical improvement and all were bacteriologically cured. Satisfactory cerebrospinal fluid bactericidal activity and drug concentrations were seen 24 hours after a dose even in those patients in whom repeat spinal taps were carried out following the last dose of therapy. The drug was well-tolerated and the major adverse effect seen was diarrhea in 20.4% of the patients. The diarrhea was mild and self limited and did not necessitate discontinuation of the drug although it was frequently associated with alterations in the stool microbiologic flora. Based on this preliminary experience, ceftriaxone, when given in a single daily dose, appears safe and effective in the treatment of bacterial meningitis in nonneonatal infants and children. PMID- 3088550 TI - A neuropsychiatric approach to impulse disorders. AB - Disordered impulse control (or pathologic impulsivity) is a common feature of many neurologic and psychiatric illnesses. Diagnosis is founded on comprehensive neuropsychiatric evaluation. Behavioral dyscontrol often represents pathology at multiple levels of nervous system function and requires an appropriately comprehensive treatment program. Evaluation and diagnostic classification are discussed. Several clinical synopses are presented to illustrate the common complexity of evaluation and treatment in presentations of pathologic impulsivity. PMID- 3088551 TI - [Mycoplasma pneumoniae as an etiological factor in pneumonia and inflammation of the mediastinal lymph nodes in children]. PMID- 3088553 TI - Free vascularized bone and muscle flaps for osteomyelitis. AB - Chronic, post-traumatic osteomyelitis remains an unsolved problem for orthopedists. With improved knowledge of skin and muscle flap circulation, surgeons are now capable of covering wide defects left by debridement. Early clinical experience with muscle and skin flaps to improve vascularity and achieve a stable, closed wound have been encouraging. Management of wounds with infected bone is primarily aimed at resection of infected or nonviable tissue. Antibiotics are of value, however are of secondary importance to a thorough debridement. It is uncertain as to whether osteomyelitis is a curable entity. However, free tissue transfer affords the surgeon the opportunity to perform a thorough debridement and achieve a stable closed wound. PMID- 3088552 TI - [Primary renal tubular acidosis in children]. PMID- 3088554 TI - Vascularized fibular grafting for the treatment of congenital pseudarthrosis of the tibia. AB - Six patients with congenital pseudarthrosis of the tibia were treated with vascularized fibula transplantation after the abnormal pseudarthrosis site had been radically debrided. At the time of surgery, the patients' ages ranged from 18 months to 5.5 years, and follow up was from 9 months to 4.5 years. All the fibular transplants healed and the patients were all fully weight bearing in a brace 6-months postoperatively. Age at fracture or surgery, site of the fracture, or radiographic appearance were not contraindications to the use of this technique. Although three of the patients required one further operation, the short- and long-term problems have been relatively minor. This technique has proven successful in managing many resistant patients with this difficult orthopedic problem. PMID- 3088555 TI - Syncope. Cost-effective patient workup. AB - Syncope is a common problem in primary care practice that presents a diagnostic challenge. Fortunately, the initial evaluation not only identifies the cause in most patients with an identifiable cause, it also defines the prognosis for these patients. A systematic history, physical examination, and 12-lead ECG are the foundation of this evaluation and provide the most cost-effective diagnostic strategy. When signs and symptoms indicate a neurologic, cardiac, or carotid sinus problem, diagnostic procedures such as angiography, electroencephalography, cardiac catheterization, echocardiography, or carotid sinus massage should be added, but only as necessary to confirm the diagnosis. At the University of Cincinnati, we monitor patients with syncope of unknown origin with 24-hour ambulatory ECG recording and interpret the results as outlined in table 2. If not referred for cardiac or neurologic consultation, these patients are evaluated every three months for a year. This approach can minimize unnecessary testing and improve patient care. PMID- 3088556 TI - Management of localized prostatic cancer. AB - The choice of radiation therapy or radical prostatectomy as potentially curative treatment for apparently localized carcinoma of the prostate is controversial. Currently, radical prostatectomy is becoming more popular. Perhaps most important to referring primary care physicians is that they choose specialists who are serious students of this disease and who have at their disposal the modern techniques that have produced the current low morbidity rates. It is especially important that the primary care physician make this choice directly and with confidence, because the nuances of the disease and our knowledge about them are very complex and can easily distress and confuse the patient and his family. PMID- 3088557 TI - Home parenteral nutrition: caveat emptor. PMID- 3088558 TI - Bursal role in the synthesis of gamma-chain messenger ribonucleic acid in young chickens. AB - Incomplete bursectomy was performed in 3-day-old chickens by treatment with .5% testosterone propionate on the 3rd day of incubation. The purpose of this experimental approach was to determine the role of the bursa of Fabricius in the translation activity of messenger ribonucleic acids (RNA) coding immunoglobulin isotypes. The bursal poly(A) RNA, prepared from bursae of normal and hormone treated chickens, directed the synthesis of 72, 43, 38, and 25-kilodalton molecules as revealed by immune precipitation and sodium dodecylsulphate acrylamide gel electrophoresis. However, unlike the messenger RNA from normal bursae, the messenger from bursae of hormonal-treated embryos failed to direct the synthesis of 68-kilodalton gamma-polypeptide. PMID- 3088559 TI - [Effect of fenoterol and disodium cromoglycate on the methacholine provocation test in bronchial asthma]. PMID- 3088560 TI - [Follow-up analysis of health pedagogic problems in child psychiatric long-term care]. PMID- 3088561 TI - Prenatal diagnosis of Hunter syndrome using chorionic villi. AB - A case of the Hunter syndrome diagnosed prenatally using chorionic villi is presented. Chorion biopsy was performed in the 10th week of pregnancy. The sample was examined for karyotype and for iduronate sulfatase activity. The fetus was male and the enzyme activity reduced to 4 per cent of normal. Termination of pregnancy occurred at the 11th week. PMID- 3088562 TI - Phototoxicity of the tetracyclines: photosensitized emission of singlet delta dioxygen. AB - The spectroscopic observation of 1268-nm emission of singlet oxygen photosensitized by tetracyclines in oxygenated solutions at room temperature is reported. In the series demeclocycline, tetracycline, and minocycline, the efficiency of singlet oxygen generation is found to parallel the clinical observation of relative frequency of phototoxicity of these antibiotics, suggesting singlet oxygen generation as the origin of their phototoxicity. PMID- 3088563 TI - Isolation of ras GTP-binding mutants using an in situ colony-binding assay. AB - We have developed a strategy to isolate mutant ras genes encoding proteins defective in GTP binding. Random in vitro mutagenesis of a v-Harvey (Ha)-ras expression vector was followed by an in situ GTP-binding assay on lysed bacterial colonies. Single amino acid substitutions at ras codon 83, 119, or 144 decreased the affinity of p21 for GTP by a factor of 25-100 primarily as a consequence of increased rates of dissociation of GTP from p21. Nevertheless, these mutant genes induced transformation of NIH 3T3 cells with efficiencies comparable to wild-type v-Ha-ras. In transformed cells, mutant p21s were phosphorylated to a degree similar to that of wild-type v-Ha-ras p21, suggesting that a decrease in affinity by a factor of 100 did not prevent the mutant ras protein from binding GTP in vivo. These results are discussed with respect to the role of GTP in the regulation of p21 function. PMID- 3088564 TI - Autonomous functions of structural domains on human tissue-type plasminogen activator. AB - Transfected mouse Ltk- cells were employed for transient expression of recombinant human tissue-type plasminogen activator (t-PA; EC 3.4.21.31) or of recombinant-t-PA deletion proteins, encoded by SV40-pBR322-derived t-PA cDNA plasmids. The t-PA cDNA deletion mutants have two features in common, i.e., cDNA programming the signal peptide and the coding region for the light chain. Consequently, recombinant t-PA mutant proteins are efficiently secreted and display plasminogen activator activity. The gene encoding the amino-terminal heavy chain [an array of structural domains homologous to other plasma proteins (finger, epidermal growth factor, and kringle domains)] was mutated using restriction endonucleases to delete one or more structural domains. The stimulatory effect of fibrinogen fragments on the plasminogen activator activity of t-PA was demonstrated to be mediated by the kringle K2 domain and to a lesser extent by the finger/epidermal growth factor region but not by the kringle K1 domain. These data correlate well with the fibrin-binding properties of the recombinant t-PA deletion proteins, indicating that the stimulation of the activity by fibrinogen fragments is based on aligning the substrate plasminogen and t-PA on the fibrin matrix. Our results support the evolutionary concept of exon shuffling, arranging structural domains that constitute autonomous functions of the protein. PMID- 3088565 TI - Antibodies to the evolutionarily conserved amino-terminal region of the v-myb encoded protein detect the c-myb protein in widely divergent metazoan species. AB - Antibodies directed against a bacterial fusion protein that contains the domain encoded by the highly evolutionarily conserved 5' one-third of the v-myb oncogene of avian myeloblastosis virus (AMV) detect the protein products of various members of the myb gene family. Immunoprecipitation or immunoblot analyses with these antibodies yielded the following information. First, the products of the v myb oncogenes of AMV (p48v-myb) and of E26 virus (p135gag-myb-ets) contain this highly conserved amino acid sequence, as previously hypothesized. Second, p75c myb, the product of the chicken c-myb protooncogene, also contains this protein domain. Third, these antibodies have identified the products of the human, murine, and Drosophila c-myb genes, which were all found to be nuclear proteins of Mr 75,000-80,000. The human c-myb protein product is present in immature cells of the erythroid, myeloid, and lymphoid lineages. PMID- 3088566 TI - Multiple cis-acting elements modulate the translational efficiency of GCN4 mRNA in yeast. AB - The expression of the GCN4 gene in yeast is regulated at the translational level: growth of yeast cells under amino acid starvation conditions results in an increase in the translational efficiency of GCN4 mRNA. A sequence within the 5' untranslated region of this mRNA, which contains four small open reading frames, acts in cis to suppress translation when growth occurs in rich media. In this report, we have analyzed the effects on translation of a series of deletion, insertion, and substitution mutations in the 5' untranslated region of GCN4 mRNA. This analysis showed that at least two distinct cis elements located within the region of the small upstream open reading frames are required, in conjunction with trans positive elements, for the translational activation of GCN4 mRNA. We propose that the translational efficiency of GCN4 mRNA is modulated by the rate of translation initiation at the upstream AUG codons. PMID- 3088567 TI - Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. AB - A monoclonal antibody to the microtubule-associated protein tau (tau) labeled some neurofibrillary tangles and plaque neurites, the two major locations of paired-helical filaments (PHF), in Alzheimer disease brain. The antibody also labeled isolated PHF that had been repeatedly washed with NaDodSO4. Dephosphorylation of the tissue sections with alkaline phosphatase prior to immunolabeling dramatically increased the number of tangles and plaques recognized by the antibody. The plaque core amyloid was not stained in either dephosphorylated or nondephosphorylated tissue sections. On immunoblots PHF polypeptides were labeled readily only when dephosphorylated. In contrast, a commercially available monoclonal antibody to a phosphorylated epitope of neurofilaments that labeled the tangles and the plaque neurites in tissue did not label any PHF polypeptides on immunoblots. The PHF polypeptides, labeled with the monoclonal antibody to tau, electrophoresed with those polypeptides recognized by antibodies to isolated PHF. The antibody to tau-labeled microtubules from normal human brains assembled in vitro but identically treated Alzheimer brain preparations had to be dephosphorylated to be completely recognized by this antibody. These findings suggest that tau in Alzheimer brain is an abnormally phosphorylated protein component of PHF. PMID- 3088568 TI - Intercontinental spread of a genetically distinctive complex of clones of Neisseria meningitidis causing epidemic disease. AB - Strains of Neisseria meningitidis responsible for an epidemic of meningococcal disease occurring in Norway since the mid-1970s and for recent increases in the incidence of disease in several other parts of Europe have been identified by multilocus enzyme electrophoresis as members of a distinctive group of 22 closely related clones (the ET-5 complex). Clones of this complex have also colonized South Africa, Chile, Cuba, and Florida, where they have been identified as the causative agents of recent outbreaks of meningococcal disease. There is strong circumstantial evidence that outbreaks of disease occurring in Miami in 1981 and 1982 were caused in large part by bacteria that reached Florida via human immigrants from Cuba. PMID- 3088569 TI - Olfactory GTP-binding protein: signal-transducing polypeptide of vertebrate chemosensory neurons. AB - The sense of smell involves the stimulation of sensory neurons by odorants to produce depolarization and action potentials. We show that olfactory responses may be mediated by a GTP-binding protein (G protein), a homolog of the visual, hormonal, and brain signal transducing polypeptides. The olfactory G protein is identified in isolated dendritic membranes (olfactory cilia preparations) of chemosensory neurons from three vertebrate species and is shown to mediate the stimulation by odorants of the highly active adenylate cyclase in these membranes. The G protein of olfactory neurons is most similar to Gs, the hormonal stimulatory GTP-binding protein. Its alpha subunit has a molecular weight of about 42,000, and it undergoes ADP-ribosylation catalyzed by cholera toxin that leads to adenylate cyclase activation. The slight difference in molecular weights of the frog olfactory and the liver Gs alpha subunits and the higher sensitivity of olfactory adenylate cyclase to nonhydrolyzable GTP analogs are consistent with the possible existence of different Gs variants. Signal amplification due to the olfactory G protein may be responsible for the unusual acuity of the sense of smell. PMID- 3088570 TI - Evolution of the immunoglobulin kappa light chain locus in the rabbit: evidence for differential gene conversion events. AB - The rabbit kappa light chain gene family is characterized by the presence of two constant region (C kappa) genes; the C kappa 1 gene encodes the constant region of the principal rabbit immunoglobulin light chain, the C kappa 2 gene being not or very poorly expressed in domestic rabbits. There exist four major K1 alleles (b4, b5, b6, and b9), which are unequally expressed in heterozygous rabbits at the K1 locus. Here, we compare the nucleotide sequences of the joining (J) clusters of the kappa light chain gene (J kappa) linked to the b4K2 locus and to the b4 and b9 alleles at the K1 locus. As for C kappa genes, there is evidence for intergenic conversion between the J kappa 1 and J kappa 2 clusters as well as maximum divergence in the expressed J segments. The b9 J kappa 1 cluster differs from its b4 counterpart in that two out of the five J kappa segments (J1 and J2) are expressed instead of only one. This implies that preferential expression of the b4 allele as compared to the b9 allele is not only correlated to the number of available J kappa pieces. The b9 J2 segment is functional in spite of the presence of a termination codon immediately upstream of its coding region. Two major structural differences were observed between the J-C intron sequences of the b9 and b4 alleles; namely a 160-base-pair deletion of an A + T-rich sequence in b9 (which also occurs in the K2 locus) and a 10-base-pair deletion plus some substitutions in the region corresponding to the mouse kappa intron activating element. These differences could underlie the lower transcriptional rate of the b9 allele. PMID- 3088571 TI - Induction of the Bacillus subtilis SOS-like response by Escherichia coli RecA protein. AB - A plasmid that expresses the Escherichia coli RecA protein partially restored DNA repair and recombination capability and induction of the SOS-like (SOB) response in a recE4 mutant of Bacillus subtilis. In the presence of DNA-damaging agents, the E. coli RecA protein induced din operon expression, Weigle-reactivation activity, and synthesis of a B. subtilis recombination protein (Recbs) analogous to RecA but was unable to stimulate prophage induction. In addition, the RecA protein was capable of inducing the SOB response in competent recE4 strains of B. subtilis, independent of exposure to DNA-damaging agents. The results suggest that (i) the SOS response of E. coli and the SOB response of B. subtilis are strikingly similar from both a phenotypic and a regulatory standpoint and that RecA and LexA protein analogs exist in B. subtilis, (ii) the Recbs protein is capable of regulating its own production, and (iii) SOS-inducing (RecA activating) signals are generated in B. subtilis following either DNA damage or the development of physiological competence. PMID- 3088573 TI - [Value of using a nursing chart in accordance with the nursing process model]. PMID- 3088572 TI - Bovine cytotoxic T-cell clones specific for cells infected with the protozoan parasite Theileria parva: parasite strain specificity and class I major histocompatibility complex restriction. AB - We present information on the specificity of three bovine cytotoxic T-cell clones reactive with lymphoblasts infected with the protozoan parasite Theileria parva. The clones were derived from peripheral blood mononuclear cells of an animal immunized with T. parva (Muguga stock), after five stimulations in vitro with an autologous parasitized cell line. The three clones belonged to the BoT8+ subset of T cells, which is similar to the human CD8+ T-cell subset. On the basis of analysis on a panel of infected target cells originating from cattle of different major histocompatibility complex (MHC) phenotypes, killing by all three clones was found to be restricted to targets bearing the class I MHC specificity KN104, which is defined by alloantiserum KNA104 and monoclonal antibody IL-A4. This class I MHC restriction was confirmed by blocking of target cell lysis with these antibodies and monoclonal antibody w6/32, which reacts with a nonpolymorphic determinant on bovine class I MHC molecules. The three clones were parasite strain specific, in that they did not kill cells of the appropriate MHC type infected with T. parva (Marikebuni stock). These findings, taken together with previous observations that immunization of cattle with T. parva (Muguga) does not provide protection against challenge with T. parva (Marikebuni), suggest that the cytotoxic T cells recognize a cell surface antigen that may be important in induction of immunity to the parasite. PMID- 3088574 TI - [The process and level of nursing in the nurse's activities]. PMID- 3088575 TI - [Situations affecting the health of the elderly at home. The unique aspects of health education and the training and use of nursing personnel]. PMID- 3088576 TI - [A theory for timely teaching]. PMID- 3088577 TI - [When is the time ripe for teaching?]. PMID- 3088578 TI - [Reflections on nurse-client communication]. PMID- 3088579 TI - [Another bill on the university education of nurses]. PMID- 3088580 TI - Experimental transplantation. PMID- 3088581 TI - Heart and heart-lung transplantation. PMID- 3088583 TI - Pancreas transplantation. PMID- 3088584 TI - Metabolism of lactose and galactose in man. PMID- 3088585 TI - Standardization of mice by litter adjustment and the use of the 14-CO2 exhalation to assess drug metabolising capacity in rats. PMID- 3088582 TI - Liver transplantation in the ciclosporin era. PMID- 3088586 TI - The effect of interleukin 3 and erythropoietin on murine megakaryocyte colony formation. PMID- 3088587 TI - Megakaryocyte colony stimulating factor: its identity to interleukin-3. PMID- 3088588 TI - Megakaryocytic regulatory factors in vivo and in vitro. PMID- 3088589 TI - Human urinary megakaryocyte colony- and thrombopoiesis-stimulating factor. PMID- 3088590 TI - Interleukin 3 is sufficient to promote murine megakaryocytic differentiation in vitro. PMID- 3088591 TI - Hemopoietic colony formation by mouse spleen cells in serum-free culture supported by purified erythropoietin and/or interleukin-3. AB - We examined colony formation by mouse spleen cells in a serum-free culture system containing purified erythropoietin (Ep), interleukin-3 (IL-3) or a combination of the two factors. Purified Ep supported erythroid colony and burst formation but did not support formation of other types of colonies. IL-3 alone did not support erythroid burst formation in culture. However, IL-3 significantly increased the number and size of erythroid bursts. IL-3 but not Ep supported megakaryocyte colony formation. Ep did not enhance megakaryocyte colony formation or megakaryocyte populations in multilineage colonies supported by IL-3. PMID- 3088592 TI - Studies on megakaryocyte potentiator: its production and some biochemical characteristics. PMID- 3088593 TI - Health care financing research. PMID- 3088594 TI - Cancer diagnosis related groups. PMID- 3088595 TI - The impact of health care economics on the selection of new radiation therapy equipment. PMID- 3088596 TI - Health care trends, DRG's and community hospital oncology units. PMID- 3088597 TI - Cost effectiveness of liver scanning in the detection of hepatic metastasis in newly diagnosed colorectal carcinoma. PMID- 3088598 TI - Clinical evidence of feasibility and efficacy of simultaneous irradiation and chemotherapy in advanced squamous cell carcinoma. PMID- 3088600 TI - Community cancer centers: organization, program and fiscal issues. PMID- 3088599 TI - An aggressive, sequential combination chemotherapy regimen in the treatment of metastatic colorectal carcinoma. PMID- 3088601 TI - Effects of polyunsaturated fatty acids and prostaglandin synthesis on renal function. AB - The effects of polyunsaturated fatty acids (phosphatidylcholine) on renal function in healthy subjects and in patients with chronic renal failure, with liver cirrhosis, and with heart failure were studied. The drug was administered at 3.5 mg/kg i.v. (Linoleic acid 1.24 mg/kg). In all cases, the administration of the drug caused an increased excretion of sodium and especially of water with a reduction in basal urinary hypertonicity. The polyuria was caused by the higher glomerular filtration rate not being counterbalanced by an increase in tubular water reabsorption. The water reabsorption was mostly anisosmotic. The presence of urinary hypertonicity excluded an inhibition of ADH secretion by this drug. The sodium excretion was probably caused by an increase of the glomerular filtration rate whereas no significant changes in the tubular reabsorption of sodium were seen. We found a significant (p 0.05) increase in PGE2 urinary excretion after phosphatidylcholine administration. Lysine - acetylsalicylate injection after phosphatidylcholine, in other trials in the same patients, prevented the effects previously reported. Therefore we suggest that the effects of this drug are mediated by an increased availability of renal prostaglandins. PMID- 3088602 TI - Platelet aggregating substance from mononuclear leukocytes. AB - Human peripheral blood mononuclear leukocytes (ML) in suspension stimulated with arachidonic acid (AA) were able to induce platelet aggregation. Shape change followed by first and second wave aggregation was the pattern of the platelet response. ML not treated with AA did not induce platelet aggregation nor did AA done at the concentration employed. The aggregating activity was not due to the ML presence, since cell-free supernatants of ML stimulated with AA induced similar platelet aggregation as the whole suspension. Aspirin incubated with ML AA produced 65% reduction of the above aggregatory activity described while 38% and 45% reduction was obtained when ML-AA was incubated with 5, 8, 11, 14 eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA). Complete platelet cyclooxygenase integrity was necessary to obtain the second wave of aggregation induced by ML-AA, while this was not required for the first wave response. We propose that ML-AA are able to produce a platelet activating substance(s) derived from AA metabolism involving cyclo and lipoxygenase actions. It is unlikely that this substance(s) is a hydroperoxyfatty acid or thromboxane A2 (TXA2) since it is active for at least two hours once generated. PMID- 3088603 TI - Contribution of lipoxygenase metabolites to IL-2 production in the early phase of lymphocyte activation. AB - Lipoxygenase inhibitors; eicosatetraynoic acid (ETYA), esculetin and caffeic acid, inhibited interleukin-2 (IL-2) production by Con A (concanavalin A) stimulated murine spleen lymphocytes. They effectively inhibited IL-2 production without affecting cell viability when they were added to the cultures within around 6 hr after Con A stimulation. IL-1 production was also inhibited effectively when the inhibitors were added within 4 hr after stimulation. Therefore, immunosuppressive characteristics of these inhibitors can in part be explained by their inhibitory effects on production of lymphokines involved in the early phase of lymphocyte activation. PMID- 3088604 TI - Evidence for the mechanism by which garlic inhibits platelet aggregation. AB - Aqueous extract of garlic inhibited aggregation induced by ADP, collagen, arachidonate (AA), epinephrine and calcium ionophore A23187 in a dose-dependent manner. In an attempt to clarify the mechanism of inhibition of aggregation, metabolism of arachidonic acid in platelets was examined in the presence of garlic extract. It was found that: garlic reduced the formation of thromboxane from exogenous AA; garlic inhibited the phospholipase activity; garlic inhibited the formation of thromboxane and lipoxygenase products formed in platelets prelabelled with AA; and garlic inhibited the incorporation of arachidonate into platelet phospholipids. These effects may explain, in part, inhibition of platelet aggregation. Further, since garlic was also effective in inhibiting aggregation induced by calcium ionophore A23187 it may be suggested that the antiaggregation effect may be related to intraplatelet mobilization of calcium. Inhibition of epinephrine-induced aggregation by garlic extract may suggest that it may be inhibiting uptake of calcium into platelets thereby lowering cytosolic calcium concentrations. Thus garlic appears to be in possession of components which might exert their effects at various stages involved in the process of platelet aggregation. PMID- 3088605 TI - Endogenously formed norharman (beta-carboline) in platelet rich plasma obtained from porphyric rats. AB - Porphyria was induced in adult male Wistar rats starved for 24 hr by SC injection of 400 mg/kg allylisopropylacetamide (AIA). The presence of porphyria was shown by measuring excretion of delta-aminolevulinic acid (delta-ALA) and porphobilinogen (PBG) into the urine during 24 hr after AIA administration. Plasma levels of glycine, serine and of a number of other amino acids were decreased in porphyric rats as compared to controls. Intraperitoneal injection of 2 mmol/kg serine 24 hr after AIA administration was used as an animal model for an acute psychosis, by measuring catalepsy scores 30 min after serine injection. The concentration of 5 different beta-carbolines in platelet rich plasma (PRP) was measured using an HPLC-fluorometric method. An increase in the concentration of norharman (NH) in PRP, ranging from 0.57 nmoles/l in control rats to 1.88 nmoles/l in serine treated porphyric rats was found. The catalepsy duration was exponentially correlated with the NH concentrations in PRP. It is concluded that an elevated conversion of serine into glycine via serine hydroxymethyltransferase (SHMT) may be responsible for the enhanced NH biosynthesis. PMID- 3088606 TI - Histidyl-proline, a rapidly degraded metabolite of thyrotropin releasing hormone, has behavioural activity. AB - The effects of intracerebroventricular (ICV) administration of histidyl-proline (His-Pro; 0, 1, 10 and 100 micrograms/rat), a rapidly degraded metabolite of thyrotropin releasing hormone (TRH), were assessed using three behavioural paradigms. Locomotor activity was significantly increased over 30, but not 90, min following administration of the highest dose. This stimulatory effect was more apparent when naive rats were tested in an open field without any prior exposure to the apparatus; the effect was attenuated on a second exposure. His Pro treated subjects also tended to prefer the area near the walls of the apparatus. The effects of the dipeptide on visual perception were studied, using a two-choice task. A low but not high (10, versus 100 micrograms/rat) dose of His Pro increased response switching, but did not affect response repetition, latencies or percent correct performance. The results indicate that His-Pro can alter behaviour by affecting motor output, as well as emotional processes. PMID- 3088608 TI - Prenatal antiepileptic drug exposure alters seizure susceptibility in rats. AB - An animal model is used to address the issue of prenatal exposure to certain antiepileptic drugs and seizure susceptibility in the offspring. Administration of doses established as median therapeutic doses in humans of phenobarbital, valproate and clonazepam to pregnant rats during the last third of gestation produced sexually dimorphic alterations in pentylenetetrazol (PTZ)-induced seizures as well as in non-convulsive (spontaneous alternation and cliff avoidance) behaviors in the offspring. Altered seizure susceptibility occurred in the absence of overtly recognizable morphological abnormalities and did not appear to reflect differences in the status of circulating drug-binding plasma proteins. Possible neural and/or metabolic mechanisms responsible for these behavioral changes are discussed. PMID- 3088607 TI - Interactions between TRH and ethanol in the medial septum. AB - When rats were pretreated with ethanol (3.0 g/kg, IP), subsequent microinjection of thyrotropin-releasing hormone (TRH) (500 or 1000 ng) into the medial septum, 30 minutes later, significantly shortened the time necessary for the rats to regain their righting reflex. Conversely, microinjection of TRH into the nucleus accumbens (1000 ng/side) or the area of the raphe obscurus (1000 ng) had no effect on ethanol-induced depression, although both of these structures mediate specific TRH effects in the CNS. In order to determine if this antagonism was due to a specific TRH interaction, TRH Fab fragments were microinjected into the medial septum just prior to the microinjection of TRH. Under these conditions, TRH did not alter ethanol's depressant actions. Finally, this TRH antagonism of ethanol-induced depression appears attributable to a net increase in neuronal activity, because electrical stimulation (160 microA, 120 Hz, 1.5 msec duration) of the medial septum antagonized ethanol's impairment of the righting reflex. These results are discussed in relationship to a potential CNS site for the action of ethanol. PMID- 3088609 TI - Effects of acute and long-term treatments with thyrotropin-releasing hormone on locomotor activity and jumping behavior in mice. AB - The acute and chronic effects of thyrotropin-releasing hormone (TRH) on ambulation and, in combination with apomorphine, on jumping behavior were investigated in mice. A single administration of TRH (1-10 mg/kg SC) produced an initial hyperactivity in a dose-dependent manner. Following administration of TRH (1-10 mg/kg SC) for 21 successive days, the stimulatory effect on locomotion progressively increased. Haloperidol exerted a biphasic action on hyperlocomotion induced by acute and repeated TRH, i.e., stimulation at lower doses (0.01-0.02 mg/kg SC) and inhibition at higher doses (0.05-1 mg/kg SC). When TRH was administered in combination with low doses of apomorphine, locomotor activity was inhibited but jumping behavior occurred. The inhibitory effect of low doses of apomorphine on locomotion was shifted from doses of 0.1-0.25 mg/kg SC of apomorphine for acute TRH (10 mg/kg) to 0.25-0.35 mg/kg for repeated TRH (10 mg/kg), whereas the stimulatory effect of higher doses of apomorphine (0.5-1 mg/kg SC) on locomotion tended to decrease with repeated TRH. Jumping behavior induced by the combined treatment of TRH and apomorphine was proportional to the dose of TRH but exhibited an inverted-U response to the dose of apomorphine. Chronic TRH (10 mg/kg) in combination with apomorphine (0.1-1 mg/kg SC) also produced jumping behavior, but the dose-response curve for apomorphine was shifted to the right. The present results suggest that repeated treatment with TRH in mice produces hyperlocomotion, despite attenuation of both pre- and postsynaptic receptor activity, and that the inhibitory effect of repeated TRH on presynaptic receptors may be more potent than that on postsynaptic receptors. PMID- 3088610 TI - Changes in nociception after 6-hydroxydopamine lesions of descending catecholaminergic pathways in mice. AB - Intrathecal (ITH) administration of 5 micrograms 6-hydroxydopamine (6-OHDA) in mice selectively lesioned descending catecholaminergic pathways. Uptake of 3H noradrenaline (3H-NA) into synaptosomes from the lumbar spinal cord was reduced by 95%, without any change in the uptake of 14C-5-hydroxytryptamine (14C-5-HT). Synaptosomal uptake of 3H-NA and 14C-5-HT in the brain was not altered. The nociceptive sensitivity was evaluated using the tail-flick, hot plate and formalin tests 3 and 14 days after injection of 6-OHDA. At day 3 hyperalgesia was found in the hot-plate test, unchanged response latency in the tail-flick test and hypoalgesia in the formalin test. At day 14 there were no statistically significant differences from controls in any of the tests. The present findings support the contention that catecholaminergic pathways participate in the tonic regulation of nociception in the spinal cord. However, while supraspinally integrated responses to acute thermal pain, as measured with the hot-plate test, are inhibited by these pathways, responses to prolonged chemical pain are enhanced. PMID- 3088611 TI - The effect of diazepam on indices of 5-HT function in man. AB - The effects of acute and chronic diazepam administration on L-tryptophan induced prolactin release was studied in seven male volunteers. Acute diazepam diminished the prolactin neuroendocrine response to L-tryptophan. On chronic administration this effect was lost, suggesting tolerance had developed. The sedative effects of L-tryptophan were unaltered by either acute or chronic diazepam administration. A possible explanation for the tolerance development to the neuroendocrine effects may be the observed reduction in platelet 3H-imipramine binding that was observed. PMID- 3088612 TI - [Antiphlogistic effectiveness of combinations of inhibitors of phospholipase A2, cyclooxygenase and lipoxygenases of the arachidonic acid cascade]. AB - Combinations of inhibitors of phospholipase A2, cyclooxygenase and lipoxygenase as the key enzymes of the arachidonic acid cascade were investigated with respect to their anti-inflammatory effectivity in the carrageenin paw edema and adjuvant arthritis of rats. Combinations of indometacin with butylhydroxytoluene, quinacrine, lidocaine or/and procaine gave additive or overadditive effects in the carrageenin edema. Addition of ascorbic acid decreased the effectivity. Similar results as with indometacin were obtained with dexamethasone. The "steroid saving effect" of the combination of a glucocorticoid with a non steroidal anti-inflammatory analgesic was confirmed in the carrageenin edema. However, it could not be found in the adjuvant arthritic rat with dexamethasone and declofenac-Na. The fitness of the models is discussed. PMID- 3088613 TI - Flavonoid inhibition of soybean lipoxygenase. PMID- 3088615 TI - [Significance of minor vectorcardiographic changes (the QRS complex)]. PMID- 3088614 TI - Some specific features of exercise stress in athletes. AB - Stress factors which can elicit several psychoemotional, neuromotor and cardiovascular reactions in athletes before or during training and competition are discussed. The authors' data concern firstly the significance of ACTH depletion. Exploration of the neuromotor system, the flicker test, evaluation of the urinary excretion of amine metabolites and several types of questionnaires (related to stress, anxiety and coronary risk factors) in a group of 35 athletes have outlined their psychophysiological reactions and behaviour. The necessity to prevent and manage distress phenomena found in 20 subjects is considered. PMID- 3088616 TI - [Effects of acute ethanol intoxication on thyroid hormones in rats]. PMID- 3088617 TI - Symmetrical-asymmetrical codons and hydrophobic-hydrophilic amino acids. AB - The symmetrical codons present in the first and third positions two purine (P) or two pyrimidine (p) bases (e.g. PNP or pNp), while the asymmetrical codons present in the first and third positions a purine and a pyrimidine base (e.g. PNp or pNP). The percentages of symmetrical and asymmetrical codons specifying hydrophobic and hydrophilic amino acids are similar in the genes of viruses and vertebrates, which utilise the "universal" genetic code, but they are different for the genes of human mitochondria and yeast mitochondria, which utilize two specific genetic codes. PMID- 3088618 TI - Effects of a seven-day hypokinesia on the digestive tract of nonpregnant and pregnant rats. AB - Hypokinesia (HK) produced by a 7-day contention of pregnant rats in small cages is followed by a discrete decrease of PAS reaction for glycoproteins in the submandibular and sublingual glands, in the mucosa of the stomach, duodenum, small intestine and colon, and also by a small but evident increase of that for leucineaminopeptidase and acid phosphatase in the duodenum and in the intestine. The moderation of these reactions may be explained by the small interval of contention, and not by pregnancy, because the changes are similar in male rats after the same interval. After a longer interval, these reactions change in the same manner but they are more evident, as results from our previous studies. They are not connected with a corticosterone hypersecretion (the principal glucocorticoid in rat) because adrenalectomy does not influence them as results from our previous research. HK increases the 4 and 5 isoenzymes of lactic dehydrogenase (LDH) in the stomach. In the small intestine appeared only the LDH 4 and 5 isoenzymes, HK increases LDH5 isoenzyme. Adrenalectomy increases all LDH isoenzymes of gastric mucosa, and in the small intestine all five fractions appeared, but with a slight activity of LDH 1 and 2. This relation between adrenal hormones and these isoenzymes must be further studied, especially after HK. After a 7-day HK, nonpregnant female rats present an augmented total gastric acid output (TAO), as previously found by us in males. After adrenalectomy this acid hypersecretion disappeared. Even smaller values for TAO were found. Pregnancy considerably increased TAO which may be due, as we have already found, to a blood pH decrease. After HK this hypersecretion decreased remaining nevertheless great. Progeni born of rats submitted to HK have, after 30 days of life, an augmented TAO. Parts of this research were carried out in order to reproduce by HK, at ground level, the 5-day orbital flight conditions of the soviet Cosmos 1514 biosatellite containing pregnant rats in which we studied some identical parameters. PMID- 3088619 TI - Histochemistry of the gastrointestinal tract in pregnant rats subjected to cosmic flight and in their progeny (Cosmos 1514). AB - Investigations were carried out in the digestive tract of pregnant rats submitted to 5 days orbital flight, as well as in rats aged 30 and 100 days, to which the pregnant experimental rats had given birth. The flight produces, in pregnant rats, a mild reduction of the glycoproteins of the salivary glands, of the gastric mucosa and the goblet cells of the small intestine, as well as an augmented activity of some intestinal enzymes. The progeny born after flight presents at 30 days a mild decrease of the glycoproteins in the sublingual gland and stomach and a slight increase in the activity of some enzymes in the small intestine. In 100-day-old rats, the differences between control and experimental group are not significant. PMID- 3088621 TI - [Hormonal and electrolytic changes due to exposure to exogenous hyperthermia and the effect of physical effort on them]. PMID- 3088620 TI - Evidence that some membrane ligands modulate the plasmalemma fluidity of endothelial cells in culture. AB - The effect of some membrane ligands on the plasmalemmal fluidity of endothelial cells from bovine aorta in culture was investigated. The ligands used were: cationic ferritin (pI 8.5), soybean agglutinin, concanavalin A, wheat germ agglutinin, as well as glutaraldehyde at different concentrations. The fluidity probe employed was 1,6-diphenyl-1, 3, 5-hexatriene (DPH) and the parameter determined to quantify the fluidity was fluorescence steady-state anisotropy. The optimum time interval required by the insertion of the fluorescent probe in plasmalemma and the appropriate density of cells in the sample were determined. Rigidisation of plasmalemma was detected following its interaction with glutaraldehyde at concentrations ranging from 0.5% to 2% (+8% to +14% relative to the controls). After exposing endothelial cells to wheat germ agglutinin, concanavalin A and cationic ferritin pI 8.5, no modifications in the steady-state DPH fluorescence anisotropy were noticed. However, plasmalemmal rigidisation of +10% to +14% relative to the controls was obtained when endothelial cells were treated with 1 mg/ml and 2 mg/ml of soybean agglutinin, respectively. The possible mechanism of membrane fluidity modulation by membrane ligands and the usefulness of such investigations are discussed. PMID- 3088623 TI - Learning ability of mice infected with different strains of scrapie. AB - CD-1 mice were infected intraperitoneally with one of 4 different strains of scrapie and tested simultaneously at or near the end of incubation. There were no differences between any of the scrapie injected groups and controls in spontaneous motor activity, or in the shock thresholds and entry latencies measured during training in a one-trial passive avoidance test. On testing, the avoidance responses were normal for the mice infected with 22C or ME7, but these mice did not show overt clinical signs (e.g., ataxia) at the time. The 139A and 79A infected mice were showing clinical signs when tested and impaired responses were found in the mice trained at a low shock threshold. However the impairment was completely overcome at a higher shock level. These results suggest that only limited reductions in learning ability are associated with some of the shorter incubation models of scrapie. Specific suggestions are made of how a learning deficit might be produced in certain scrapie models which could be useful in studies of some aspects of dementia. PMID- 3088622 TI - Norepinephrine and amino acids in prepyriform cortex of rats fed imbalanced amino acid diets. AB - Monoamines and amino acids were measured in anterior prepyriform cortex (PPC) and anterior cingulate cortex (CC) of male Sprague-Dawley rats after they were offered basal, imbalanced (IMB) or corrected amino acid diets, limited in threonine (THR) or isoleucine (ILE). In the THR study, brains were taken after 2.5 hr of feeding, when intake of THR-IMB was just depressed. In the ILE study the brains were taken after 3.5 hr on ILE-IMB, a less severely imbalanced ration, before the onset of food intake depression. The PPC has been shown to be involved in the acute response of animals to imbalanced amino acid diets. In the PPC from the IMB diet groups, NE was reduced by 30%, but the other monoamines were unchanged. In CC, an area involved in the adaptive, but not the acute feeding response to imbalanced diets, the monoamines were unchanged in the IMB diet groups. In both studies, in both tissues, the limiting amino acids were decreased in the IMB groups, although the decrease of ILE in the CC failed to reach significance. The remaining indispensable amino acids, added to create the imbalance, were slightly reduced in the THR-IMB group, but not in the ILE-IMB group in both tissues. Thus, the amino acid patterns were altered in the PPC and CC, as they are in whole brains from animals fed imbalanced amino acid diets. These results also suggest that the concentration of NE in the PPC may be associated with the initial food intake response of animals to imbalanced amino acid diets. PMID- 3088624 TI - Indole alkaloids from Tabernaemontana elegans. PMID- 3088625 TI - Allocation of scarce resources: a challenge for American medicine. AB - We must decide as a society how much we can afford, or at least are willing to spend, on health care as opposed to other goods. More importantly, how shall we decide which individual medical needs are to be met? PMID- 3088626 TI - Case finding for at risk drinking in general practice: cost-benefit analysis. AB - There is an increasing need for early detection strategies to take a part in the daily routine of general practice. A cost-benefit analysis is performed for the use of the CAGE questionnaire in case finding for at risk drinkers among general practice attenders. The questionnaire is shown to be of advantage to the general practitioner over and above his usual diagnostic methods. PMID- 3088627 TI - Task motivation and problem appraisal in long-term psychiatric patients. AB - Severely handicapped psychiatric patients in long-term day care were questioned about their perceptions of their skills, motivation to perform a range of everyday tasks, current problems and coping strategies. Patients were found to respond reliably and consistently to these questions. It is argued that effective service planning must take account of patients' views of their difficulties and, in particular, of their subjective priorities. PMID- 3088628 TI - Patterns of ethanol and water consumption as a function of restricted ethanol access and feeding condition. AB - Sixteen male albino rats were divided into two groups of eight animals and maintained at either their free-feeding or at 80% of their free-feeding weight. For four animals, access to 8% ethanol was unrestricted, for the remaining four, access was restricted to eight 20-min access periods per day. Mean amounts of ethanol consumed per bout were greater during restricted access than during unrestricted access for food-deprived animals but not for free-feeding animals. Total daily ethanol consumption was greatest when animals were food deprived and access to ethanol unrestricted. Total fluid consumption and the within session distribution of water and ethanol responding were affected by feeding condition. For food-deprived animals, the amount of water consumed per session remained relatively constant. The increase in ethanol consumption over sessions resulted in an increase in total fluid consumption. For the free-feeding animals, increases in ethanol consumption resulted in decreases in water consumption so that total fluid consumption remained constant. In addition, food-deprived animals consumed all their daily water intake at the beginning of each session when food was present. Free-feeding animals consumed water throughout the session. PMID- 3088629 TI - Central muscarinic effects of physostigmine on mood, cardiovascular function, pituitary and adrenal neuroendocrine release. AB - The mechanism by which physostigmine exerts its behavioral, neuroendocrine and cardiovascular effects was explored in two separate experiments. In the first, the centrally-acting cholinesterase inhibitor physostigmine was compared with the non-centrally-acting agent neostigmine. In contrast to physostigmine, neostigmine caused no effects. In the second experiment, pretreatment with scopolamine, in contrast to methscopolamine, attenuated physostigmine's effects. The results suggest that physostigmine exerts its effects via a central muscarinic mechanism. PMID- 3088630 TI - Behavioural and pharmacological dissociation of chlordiazepoxide effects on discrimination and punished responding. AB - Effects of chlordiazepoxide (CDP) and ethanolamine-O-sulphate (EOS) alone and in combination were tested on the acquisition and performance of continuous reinforcement - time out (CR-TO) and variable interval reinforcement - time out (VI-TO) operant discriminations in rats. CDP disrupted acquisition of CR-TO discrimination; effects were short lived, and neither CR-TO performance nor its reversal were impaired. Acquisition of VI-TO discrimination was increasingly impaired, and performance disrupted in pre-trained animals. EOS alone was inactive, and with CDP exerted only slight interactive effects. When a conflict component was added to the VI-TO schedule, however, EOS showed substantial additive effects with CDP on punished responding. The results suggest that CDP induced increases in non-rewarded (TO) responding were related to task difficulty, pointing to a discrimination impairment rather than an anxiolytic effect. In addition, the specificity of EOS potentiation may reflect a pharmacological dissociation between CDP effects on discrimination and on punished responding, and suggest that GABA is selectively involved in resistance to punishment. PMID- 3088631 TI - The effect of phenobarbital and carbamazepine on the ethanol withdrawal reaction in the rat. AB - The effects of phenobarbital (PB) and carbamazepine (CZ) on the ethanol withdrawal reaction in the rat were investigated in a blind study including an untreated control group. Physical ethanol dependence was established by intragastric intubation during a 4-day period. Both the degree of intoxication and the withdrawal reaction were assessed by standardised assessment instruments. Treatment with PB (40-60 mg/kg) and CZ (80-120 mg/kg) was initiated 10 h after the last ethanol dose and continued during the first 24 h of withdrawal. Serum concentrations of the drugs were measured. Both PB and CZ significantly reduced the ethanol withdrawal reaction compared to controls, and PB was significantly more effective than CZ. The degree of drug intoxication signs assessed by the same rating scale as the degree of ethanol intoxication indicated that maximum tolerable drug doses were used. PB probably exerts its treatment effect through the mechanism of cross dependence with ethanol, while CZ may exert a more specific effect on limbic structures responsible for central nervous system excitability. PMID- 3088632 TI - Some behavioural and EEG effects of ascorbic acid in rats. AB - Ascorbic acid (50-200 mg/kg IP) activated gross behaviour and EEG of rats. The behavioural excitation induced by d-amphetamine (2.5 mg/kg SC) was significantly potentiated by ascorbic acid (100-200 mg/kg IP). Catalepsy induced by haloperidol (0.25 mg/kg IP) was attenuated by ascorbic acid (50-200 mg/kg IP) while pentobarbitone (20 mg/kg IP)-induced sleep in rats was dose-dependently antagonised by ascorbic acid (50-400 mg/kg IP). Ascorbic acid (50-400 mg/kg IP) desynchronized the EEG of the frontal cortex and optic cortex while the EMG activity was slightly enhanced in the rat. Ascorbic acid (100 mg/kg IP) potentiated d-amphetamine (2.5 mg/kg SC)-induced EEG desynchronization and EMG activation in the rat. These results indicate that ascorbic acid exerts stimulatory effects in rats. The results also suggest that dopaminergic mechanism may contribute indirectly or directly to the observed behavioural and EEG effects of ascorbic acid. PMID- 3088635 TI - Which smokers report most relief from craving when using nicotine chewing gum? AB - Seventy-seven smoker clinic clients who managed at least 2 weeks of smoking abstinence while chewing 2 mg nicotine gum reported the degree to which the gum reduced their craving for cigarette, their daily gum consumption and the extent of urges to smoke despite the gum. Greatest relief from craving by the gum was reported by smokers with higher pre-abstinence expired-air carbon monoxide (CO) concentrations and higher "stimulant" and "dependent" scores on a smoking motivation questionnaire but not greater usual daily cigarette consumption. Gum consumption correlated positively with expired-air CO, usual daily cigarette consumption, and "stimulant" and "dependent" smoking scores. Despite the gum, urges to smoke and difficulty not smoking were reported and the severity of these was associated with "indulgent", "stimulant" and "dependent" smoking scores but not CO or usual daily cigarette consumption. The results are discussed in terms of the possible role of pharmacological and non-pharmacological factors in craving. PMID- 3088633 TI - Clonidine--induced behavioural despair in mice: reversal by antidepressants. AB - The effects of various alpha 2 adrenoceptor agonists on forced swimming-induced despair behaviour were studied in mice. Clonidine, B-HT 920 and guanfacine significantly prolonged the total immobility duration. Clonidine-induced behavioural despair was antagonized by prior treatment with yohimbine. The tricyclic antidepressants imipramine, desipramine, trimipramine, amitriptyline, nortriptyline and doxepin, the MAO inhibitor tranylcypromine, and the antimanic agent lithium reversed clonidine-induced behavioural despair. Chronic treatment with imipramine evoked more pronounced reversal as compared to acute treatment. Amphetamine, a psychostimulant, inhibited clonidine-induced enhancement of immobility duration but diazepam, a skeletal muscle relaxant was without any effect. On the other hand, adenosine showed potentiation of the submaximal response of clonidine. These observations suggest that clonidine-induced behavioural despair is probably mediated through its presynaptic action on alpha 2 adrenoceptors, resulting in reduced central noradrenergic outflow. The present data proposes a simple test system to induce depression-like syndrome in animals, sensitive to antidepressant therapy. PMID- 3088636 TI - Human cognitive function following binedaline (50 mg and 100 mg) and imipramine (75 mg): results with a new battery on tests. AB - The effects of two single oral doses of binedaline (50 and 100 mg), imipramine (75 mg) and placebo were compared on a range of psychological tasks (logical reasoning, the Stroop test, and five-choice serial reaction) in healthy young volunteers. The tasks, together with a mood adjective check-list, were completed prior to drug administration and 1, 2, 4 and 8 h post-dose. Binedaline had no significant effect on any of the task parameters. Imipramine impaired performance on all but the Stroop test at 2 h after drug administration. At 1, 2 and 4 h, ratings on the "deactivation" dimension of the mood adjective check-list were significantly higher following imipramine when compared to placebo. The results are discussed in terms of some general considerations about the selection and scoring of tasks to be used in the screening of drugs. PMID- 3088634 TI - Effects of haloperidol and nomifensine on the visual aftereffects of tilt and movement. AB - An antipsychotic and two antidepressant drugs were studied for their effects on the visual aftereffects of tilt and movement in normal volunteers. Compared with placebo, haloperidol reduced the aftereffects. The antidepressant nomifensine enhanced the tilt but not the movement aftereffect, while maprotiline (another antidepressant) had no significant effect on either aftereffect. Control experiments showed that these changes were unlikely to have resulted from drug induced alterations in scanning eye movements during adaptation. The results are discussed with reference to possible dopaminergic influences on the visual system, and to some of the symptoms of schizophrenia. PMID- 3088637 TI - The effect of the beta-carboline FG 7142 on the behaviour of male rats in a living cage: an ethological analysis of social and nonsocial behaviour. AB - The effects of FG 7142, a beta-carboline benzodiazepine receptor partial inverse agonist, on the social behavior of pair-housed rats were investigated. Four 6-min dyadic social encounters in a living cage were observed in a paradigm in which one member of a pair of rats was injected. The four injection groups (n = 8) were vehicle control, and FG 7142 at 2.5, 5.0 and 10.0 mg/kg, respectively. All injections were administered 2 min before the start of the first observation trial. Compared to the effects of vehicle alone, FG 7142 decreased aggressive behaviour but did not change the level of total social interaction. Thus there were compensating increases in approaching and avoiding behaviours following the administration of FG 7142. Locomotion declined marginally and immobility increased in FG 7142-injected rats. FG 7142 decreased the incidence of self grooming. The evidence is consistent with a relatively selective reduction in intraspecies aggression in male rats after the injection of the beta-carboline inverse agonist. PMID- 3088639 TI - Dissociation of the anorectic actions of 5-HTP and fenfluramine. AB - The possible peripheral anorectic actions of 5-hydroxytryptophan (5-HTP) and fenfluramine were examined in food-deprived rats. In a 1-h feeding test the peripherally acting 5-HT antagonist, xylamidine, attenuated the reductions in food intake induced by 5-HT and 5-HTP but not fenfluramine. Thus, the anorectic action of 5-HTP appears to be mediated in part by peripheral 5-HT receptors. Microstructural analyses showed that 5-HTP and fenfluramine induced decreases in eating rate and bout size. Xylamidine reversed the effect of 5-HTP on eating rate, and induced a slight increase in bout size in its own right. Therefore, the peripheral effect of 5-HTP appears to be a slowing of eating rate. No effects of xylamidine on fenfluramine induced changes in feeding were observed. The results indicate a dissociation of the anorectic effects of 5-HTP and fenfluramine based on a peripheral action of 5-HTP. The peripheral action of 5-HTP differs from the previously reported reductions in bout size and bout duration induced by 5-HT. Possible mechanisms for this difference in the peripheral actions of 5-HT and 5 HTP are discussed. PMID- 3088640 TI - Comparison of the pharmacologic effects of N-allylnormetazocine and phencyclidine: sensitization, cross-sensitization, and opioid antagonist activity. AB - The effects of phencyclidine (PCP) on locomotor activity were compared to those of the stereoisomers of N-allylnormetazocine (NAN) after acute administration to rats. PCP produced swaying and falling movements, increased sniffing behavior, and enhanced horizontal locomotor activity. d-NAN also induced swaying, falling, sniffing behavior and locomotion, and decreased rearing behavior. l-NAN decreased rearing activity, depressed locomotion, antagonized morphine antinociception and precipitated the morphine-withdrawal syndrome. Sensitization to drug-induced sniffing, rearing and locomotion developed after four daily injections of PCP, d NAN or l-NAN in rats. Rats which were sensitized to PCP-induced locomotion, sniffing, and rearing were also cross-sensitized to both d-NAN and l-NAN. Animals sensitized to the effects of either d- or l-NAN exhibited cross-sensitization to PCP. There was little evidence that the cross-sensitization between the three agents was stereoselective. These data indicate that the acute effects of PCP are similar to those of d-NAN, but differ from l-NAN, the only agent of the three with opioid antagonist properties. The data further indicate that as sensitization to the motor effects develops during repeated administration of PCP, d-NAN or l-NAN, the differences among the three agents become less apparent. PMID- 3088638 TI - BRL 20596, a novel anilide with central dopamine antagonist activity. AB - BRL 20596 (N-(4-amino-5-chloro-2-methoxyphenyl)-1-phenylmethyl-4-piperidine carbox amide) is a novel anilide related to clebopride (a gastric prokinetic benzamide) in which the sole change is reversal of the amide bond. Previous studies have shown conformational and electronic differences between these molecules which result in the anilide losing its gastric prokinetic activity, whilst retaining its central nervous system activity. Pharmacological and biochemical properties of BRL 20596 are compared here in animals with chlorpromazine, clebopride, haloperidol and sulpiride. BRL 20596 potently inhibited a number of behaviours, such as conditioned avoidance, amphetamine induced stereotypy and turning, and apomorphine-induced climbing. Homovanillic acid (HVA) levels in the striatum and nucleus accumbens were raised at similar dose levels to those which inhibited these behaviours, whilst sedative activity was only exhibited at much higher dose levels. Haemodynamic changes were only observed with high IV doses of BRL 20596. Much lower doses of sulpiride were needed to raise prolactin levels than to raise HVA levels. This was not the case with BRL 20596 and the other drugs, where the doses needed for the two effects were similar. The results suggest that BRL 20596 is a central dopamine antagonist, with low sedative and haemodynamic activity. PMID- 3088641 TI - The effects of nicotine chewing gum on the sensitivity to muscle tension. AB - It has been shown that smoking can alter the sensitivity to muscle activity in female smokers. The present study was designed to assess the effects of smoking cessation and nicotine replacement on sensitivity to muscle tension. Twenty-five women were randomly assigned to one of two groups. One group was given nicotine chewing gum during the withdrawal period and a second group was given no nicotine replacement. Results showed a significant difference in sensitivity at post-test for subjects given nicotine gum compared to subjects receiving no nicotine replacement. These results are consistent with the hypothesis that nicotine alters sensitivity to muscle tension. PMID- 3088642 TI - Acute marijuana effects on social conversation. AB - The present study assessed the acute effects of smoked marijuana on social conversation. Speech quantity was recorded continuously in seven moderate marijuana users during separate 1 h experimental sessions following the paced smoking of 0, 1.01, 1.84, and 2.84% THC marijuana cigarettes. Subjects engaged in conversation with undrugged partners who smoked placebo marijuana cigarettes. The active marijuana produced significant decreases in speech quantity, increases in heart rate, and increases in self-reports of "high" and sedation. Partners showed no effects in speech quantity or self-reports of drug effects that were systematically related to the doses administered to the subject pair members. The effects on speech quantity observed in the present study after acute dosing are similar to the effects on social conversation reported previously during chronic marijuana dosing. Marijuana appears to be an exception to the general rule that drugs of abuse increase verbal interaction. PMID- 3088643 TI - Repeated testing attenuates conditioned place preference with cocaine. AB - Cocaine-treated rats acquired a preference for cocaine-associated contextual stimuli (CS) relative to saline-injected control rats. However, when animals were given repeated tests for conditioned place preference intermittent between conditioning trials, they displayed an attenuation in strength of conditioning. This attenuation was not due to pharmacologic tolerance (Experiment 1), but rather reflected a disruption in learning due to exposure to the CS alone (Experiment 2). Like other examples of classical conditioning, the strength of the conditioned response (CR) as assessed by the conditioned place preference model may be influenced by partial reinforcement. PMID- 3088644 TI - Possible mediation of catecholaminergic pathways in the antinociceptive effect of an extract of Cannabis sativa L. AB - An extract of cannabis (5 and 15 mg/kg expressed as delta 9-THC) orally administered to rats caused an elevation of the nociceptive threshold (tail-flick latency and vocalization tests). Naloxone and naltrexone (blockers of mu-type opiate receptors) as well as MR 1452 (blocker of kappa opiate receptors) did not prevent the antinociceptive effect of cannabis when used at the dose of 2 mg/kg SC; only a high dose (10 mg/kg SC) of these narcotic antagonists partially blocked cannabis antinociception. ICI 154, 129, an antagonist of delta-type opiate receptors, failed to prevent the cannabis-induced rise in nociceptive threshold when used at a dose of 2 mg/kg SC but produced a significant effect at 10 mg/kg SC. While the role of opiate receptors does not seem fundamental to cannabis antinociception, the clear-cut effectiveness shown by 6-hydroxydopamine (a neurotoxin which causes a degeneration of catecholamine-containing terminals) in reducing cannabis antinociception is indicative of a participation of catecholamines in the phenomenon. PMID- 3088645 TI - Receptor binding of N-(methyl-11C) clozapine in the brain of rhesus monkey studied by positron emission tomography (PET). AB - By means of positron emission tomography the uptake and kinetics of N-(methyl 11C)clozapine in different brain regions have been studied in Rhesus monkeys. 11C clozapine rapidly entered the brain and maximum radioactive uptake was seen 5-12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of 11C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for 11C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug. PMID- 3088646 TI - Similar effects of antidepressant and non-antidepressant drugs on behavior under an interresponse-time greater than 72-s schedule. AB - Antidepressant drugs were reported to decrease responses and increase reinforcements in water-deprived male albino rats pressing a lever for water on a schedule requiring a pause of at least 72 s between responses (IRT greater than 72). Subsequently other investigators, using food-deprived ovariectomized hooded rats pressing a lever for food, showed that antipsychotic drugs produced the same effect as antidepressants. Because methodologies differed somewhat, the present study was designed to replicate closely the experimental conditions of the original studies, e.g., same strain and sex, same reinforcer, similar baseline behavior. In this study the antidepressant imipramine, the antipsychotics chlorpromazine and haloperidol, and to some extent the anxiolytic buspirone produced qualitatively similar effects - decreased responses and increased reinforcements - although there were some quantitative differences. This result, and other results showing that some antidepressants increase responses and decrease reinforcements, suggest that the IRT greater than 72-s task lacks specificity as a screening method for antidepressants. PMID- 3088647 TI - Antagonism of apomorphine-induced yawning by SCH 23390: evidence against the autoreceptor hypothesis. AB - The ability of apomorphine to induce yawning (YWG) in normal and reserpinized rats and its interaction with SCH 23390, a potent and specific D-1 receptor antagonist, was studied. Apomorphine was more potent in inducing YWG in reserpine pretreated as compared to control rats. SCH 23390, in low doses (0.05 mg/kg SC), was able to significantly reduce the YWG evoked by apomorphine both in control and in reserpine-pretreated rats. The results indicate that D-1 receptors contribute to YWG elicited by apomorphine and contradict the idea that this effect is mediated by DA autoreceptors. PMID- 3088649 TI - A conditioned anti-parkinsonian drug effect in the hemi-parkinsonian rat. AB - In two separate experiments contralateral rotation was classically conditioned in hemi-Parkinsonian rats. In the first experiment, ten rats with unilateral 6 hydroxydopamine lesions of the substantia nigra, which produced ipsiversive circling, were given five daily injections of the dopamine receptor agonist apomorphine (0.5 mg/kg) to induce circling contralateral to the lesion hemisphere. One half of the rats (the conditioning group) were placed in a novel environment for 15 min during each apomorphine treatment. Subsequently, when placed into this environment 3, 10, 17, and 24 days after the final apomorphine injection, the conditioning group spontaneously rotated contralateral to the lesion hemisphere, whereas a similarly drug-treated non-conditioned group spontaneously rotated ipsilateral to the lesion hemisphere. On day 26, all rats were given a 2.0 mg/kg injection of d-amphetamine, which generated ipsilateral rotation in all rats in their home environment, but when placed in the conditioning environment, the conditioned group rotated contralateral whereas the non-conditioned group rotated ipsilateral. In the second experiment, eight rats with unilateral destruction of dopamine neurons were given differential conditioning in two novel environments. In every case, environments associated with 0.5 mg/kg apomorphine treatment induced contralateral rotation when the rats were tested without drug but ipsilateral rotation in environments not associated with apomorphine. These findings suggest a role for respondent or Pavlovian conditioning in the pharmacological management of Parkinsonism. PMID- 3088648 TI - Naloxone does not affect cigarette smoking. AB - In order to provide information about the hypothesis that endogenous opioids mediate the reinforcing properties of cigarette smoking, the present study examined the effects of naloxone, an opioid antagonist, on cigarette smoking in seven normal volunteers. The study used experimental procedures that had previously been shown sensitive for detecting the effects of other drugs, (including a nicotine antagonist) on smoking. Isolated subjects smoked their regular brand of cigarettes freely in a naturalistic laboratory environment while watching television or reading. Sixty minutes before each 2 h smoking session subjects received an IM injection of naloxone HCl (0.0625, 0.25, 1.0, or 4.0 mg/kg) or placebo. Each subject received each treatment three times in a mixed order across days. Naloxone did not significantly affect any measure of cigarette smoking including number of cigarettes, number of puffs, or expired air carbon monoxide level. Naloxone did, however, produce significant dose-related increases in subject ratings of yawning, stretching, and relaxation. The results of the present study provide no support for the endogenous opioid theory of smoking reinforcement. PMID- 3088651 TI - Concentrations of thioridazine and thioridazine metabolites in erythrocytes. AB - The concentrations of thioridazine and its main metabolites in erythrocytes from 61 thioridazine-treated patients were determined by gas-liquid chromatography. The mean and range of the erythrocyte concentrations, expressed as percentage of the corresponding plasma concentrations, were: thioridazine, 5.1% (2.0-10.6); side-chain sulfoxide, 5.6% (1.6-10.4); side-chain sulfone, 3.3% (1.1-6.8); ring sulfoxide 2.7% (0.8-4.9). The erythrocyte and plasma concentrations were significantly correlated. The erythrocyte/plasma concentration ratios, all the erythrocyte concentrations, but none of the plasma concentrations except ring sulfoxide were significantly positively correlated to the dose of thioridazine. The erythrocyte/plasma concentration ratio was not correlated to age. In vitro experiments indicated no clinically relevant erythrocyte-mediated oxidation of thioridazine. PMID- 3088650 TI - Pharmacological modification of DDT-induced tremor and hyperthermia in rats: distributional factors. AB - Pretreatment of rats with hydantoin (75 mg/kg, PO, an anticonvulsant), trihexyphenidyl (10 mg/kg, SC, a muscarinic cholinergic antagonist), or piperonyl butoxide (500 mg/kg, PO, a metabolic inhibitor) had no effect on the whole blood or brain tissue levels of orally administered DDT (75 mg/kg) or its metabolites DDD and DDE. Hydantoin and piperonyl butoxide decreased DDT-induced tremor and hyperthermia due to DDT when measured 12 h after DDT exposure, while trihexyphenidyl augmented some components of DDT-induced tremor. Additional experiments found that pretreatment with piperonyl butoxide increased tremor due to permethrin exposure (120 mg/kg, PO), while having no effect on tremor due to chlordecone administration (60 mg/kg, IP). Pretreatment with ellipticine (30 mg/kg, IP, a metabolic inhibitor) also decreased tremor 12 h after DDT exposure. The effects of piperonyl butoxide and ellipticine on DDT-induced tremor are postulated to occur through direct actions of these compounds on nerve or muscle tissue. Hydantoin-induced attenuation of DDT-induced neurotoxicity may be due to the ability of hydantoin to block repetitive firing of nerves by binding to the inactivation gates of sodium. PMID- 3088652 TI - Influence of the time of administration of dexamethasone 0.25 mg on cortisol secretion in normal humans. AB - Single low doses (0.25 mg) of dexamethasone were given at 11 p.m., 2, 5 and 8 a.m. on separate days to five normal subjects. The concentrations of cortisol in plasma on the next day were significantly decreased compared to results after placebo administration, and cortisol suppression was maximal after dexamethasone had been given at 8 a.m. Our findings suggests that the postulated phase-advance of circadian rhythms is not a major cause of cortisol non-suppression in depressives given dexamethasone. PMID- 3088653 TI - Reversal of scopolamine-induced amnesia of passive avoidance by pre- and post training naloxone. AB - In a series of five experiments, the modulating role of naloxone on a scopolamine induced retention deficit in a passive avoidance paradigm was investigated in mice. Scopolamine, but not methyl scopolamine (1 and 3 mg/kg), induced an amnesia as measured by latency and duration parameters. Naloxone (0.3, 1, 3, and 10 mg/kg) injected prior to training attenuated the retention deficit with a peak of activity at 3 mg/kg. The effect of naloxone could be antagonized with morphine (1, 3, and 10 mg/kg), demonstrating the opioid specificity of the naloxone effect. Post-training administration of naloxone (3 mg/kg) as a single or as a split dose also attenuated the scopolamine-induced amnesia. Control experiments indicated that neither an increase in pain sensitivity (pre-training naloxone) nor an induced aversive state (post-training naloxone) appear to be responsible for the influence of naloxone on the scopolamine-induced retention deficit. These results extend previous findings implicating a cholinergic-opioid interaction in memory processes. A possible mechanism for this interaction involving the septo hippocampal cholinergic pathway is discussed. PMID- 3088654 TI - The discriminative stimulus and subjective effects of d-amphetamine, phenmetrazine and fenfluramine in humans. AB - The discriminative stimulus (DS) and subjective effects of d-amphetamine (AMP), phenmetrazine (PMT) and fenfluramine (FFL) were studied in a group of normal healthy adults. Subjects (N = 27) were trained to discriminate between placebo and 10 mg AMP (PO). Fourteen of the subjects (discriminators) reliably learned the discrimination, whereas the other 13 did not. Nearly all discriminators labelled AMP as a stimulant, and AMP, relative to placebo, increased ratings of drug liking and general activity level, and produced typical stimulant-like subjective effects, as measured by the Profile of Mood States, the Addiction Research Center Inventory, and a series of visual analog scales. The discrimination accuracy of discriminators increased as a function of hour after drug ingestion, as did analog ratings of how certain subjects were that their discrimination responses were correct. Discriminators were tested with doses of PMT (25 and 50 mg) and FFL (20 and 40 mg) to determine whether the DS properties of these drugs would substitute for those of AMP. Both doses of PMT consistently substituted for AMP, and PMT produced subjective effects very similar to those of AMP. Conversely, neither dose of FFL consistently substituted for AMP, and FFL produced essentially no subjective effects. These findings are consistent with results from discrimination studies with other species, and provide further evidence of the validity of this procedure for studying the DS properties of drugs in humans. PMID- 3088655 TI - Haloperidol facilitates memory retrieval in the rat. AB - Rats were trained in a complex maze task for food reward. After a 25-day retention interval, they made more errors than at the last training trials. This forgetting was alleviated by pretest treatment with haloperidol. The same dose of haloperidol had no effect on acquisition or performance when injected during training. The results were replicated, but smaller doses were found to be inactive. The possibility that the effect might be mediated through the noradrenergic system is considered. PMID- 3088656 TI - Lithium and bupropion antagonise the phasic changes in locomotor activity caused by dopamine infused into the rat nucleus accumbens. AB - Dopamine infused persistently (25 micrograms/24 h for 13 days) into the nucleus accumbens of rat brain caused phasic increases in spontaneous locomotor activity during the period of infusion. This phasic responding was prevented by lithium administered throughout the infusion period in divided doses (3 X daily administrations of 2.5 mg/kg IP) or as a continuous IP infusion (7.5 mg/kg/24 h), and by bupropion treatment (5-20 mg/kg 3 X daily). In contrast, imipramine, amitriptyline and nomifensine failed to prevent the phasic locomotor response to dopamine at doses which did not by themselves cause marked motor changes. Locomotor activity was measured using individual photocell cages, and rats preselected to (-)NPA were those initially showing a modest locomotor activity. Fourteen to twenty-eight days after discontinuing the dopamine infusion rats showed increased responsiveness to (-)NPA which persisted throughout the remainder of the 70-day withdrawal period. This long-term change was prevented when lithium was given continuously throughout the period of dopamine infusion, but not when lithium was given in divided doses, showing the importance of the mode of drug delivery. The long-term change caused by the dopamine infusion could also be prevented by bupropion but not by imipramine, amitriptyline or nomifensine to show again that the actions of classical antidepressant drugs may be differentiated from those of lithium and bupropion. Therefore, it is suggested that the model of phasic hyperactivity described may provide a means for more closely analysing, both behaviourally and biochemically, the site and mechanism of action of lithium (and bupropion) in the control of the short- and long-term consequences of an enhanced mesolimbic dopamine activity. PMID- 3088657 TI - Tolerance to effects of morphine without cross tolerance to effects of clonidine on schedule-controlled behavior of pigeons. AB - Schedule-controlled responding was maintained under a multiple fixed-interval, fixed-ratio schedule in pigeons. Dose-related decreases in response rates were produced by clonidine (0.001-0.1 mg/kg) and morphine (0.3-5.6 mg/kg). Chronic administration of morphine produced (1) tolerance to effects of morphine, as evidenced by a decrease in potency of morphine and (2) sensitivity to opioid antagonists, as evidenced by an increase in potency of naloxone. Dose-effect curves for clonidine were not appreciably altered by chronic morphine administration. PMID- 3088658 TI - An analysis of the paradoxical effect of morphine on runway speed and food consumption. AB - A previously reported paradigm in which rats run down a runway for food reward followed by morphine injection was analyzed to assess the utility of the paradigm in studies of opiate reinforcement. One experiment replicated the original report that post-trial morphine caused both an increase in runway speed and a decrease in food consumption (taste aversion) over successive trials, and showed in addition that the increase in runway speed did not occur as a result of food deprivation alone, but required the animals to have consumed food in the goal box. A second study using the quaternary opiate antagonist methyl naltrexone to block the peripheral effects of morphine suggested that the increase in runway speed has a peripheral locus while the taste aversion has a central one. A third experiment in which morphine was microinjected into either the lateral ventricle or the ventral tegmental area supported these observations, in that intracranial morphine failed to result in an increased runway speed, but did produce taste aversion after microinjection into either site. These findings also suggest that the increase in runway speed caused by post-trial morphine in this experiment has a peripheral locus of effect, which is probably distinct from the central effect that supports morphine self-administration and conditioned place preference. PMID- 3088659 TI - Phencyclidine-induced retrograde amnesia in mice. AB - The amnesic action of phencyclidine (PCP) was investigated in mice using a passive avoidance- and escape-learning method. PCP (10-30 mg/kg) administered immediately after the training test dose-dependently shortened and prolonged the step-down latency and escape latency, respectively in the retention test. There was a significant inverse relationship between the step-down and escape latencies, indicating that PCP had induced amnesia. The amnesic actions of PCP were retrograde, being observed when mice were given PCP within 10 min but not more than 30 min after the training test. The amnesic effects of PCP on both variables were antagonized significantly by physostigmine and naloxone, whereas cyproheptadine and haloperidol had no effect. None of these drugs by themselves affected passive avoidance- or escape-learning performance. These results suggest that the retrograde amnesic actions of PCP were produced via either the cholinergic or the opioidergic systems or both, but not through the serotonergic and the dopaminergic systems. PMID- 3088660 TI - Prolonged cataleptogenic effects of potentized homoeopathic drugs. AB - The four homoeopathic drugs, Gelsemium, Cannabis Indica, Graphites and Agaricus Muscarius, administered orally in 30th and 200th potencies on white rats, enhanced restraint-induced catalepsy in a similar manner to the two standard drugs pilocarpine and haloperidol (IP injection at 5 mg/kg). All the drugs tested differed from each other in the duration of cataleptogenic effect, which was more prolonged with Cannabis, Graphites and Agaricus than with Gelsemium and the two non-homoeopathic drugs used. The 200th potency of any homoeopathic drug tested acted longer than its 30th potency. PMID- 3088661 TI - Anatomical disassociation of amphetamine's rewarding and aversive effects: an intracranial microinjection study. AB - Amphetamine has rewarding properties in some behavioral paradigms, such as self administration and conditioned place preference (CPP), but an aversive component is also apparent when the drug is tested with the conditioned taste aversion (CTA) paradigm. The present study was an attempt to determine the neuroanatomical substrates of the drug's rewarding and aversive effects. Previous evidence suggested that amphetamine's stimulation of activity in dopaminergic synapses is critical for both effects. Amphetamine was therefore micro-injected bilaterally (10 micrograms/0.5 microliter per side) into six different dopaminergic sites, each in a different group of animals: the medial prefrontal cortex, nucleus accumbens, anteromedial caudate nucleus, lateroventral caudate nucleus, amygdala, and the region subjacent to the area postrema (AP region). The effects of these injections in both the taste and place conditioning paradigms were examined in separate experiments. Of the six sites, a significant CPP was observed only with accumbens injections and a significant CTA was observed only with AP region injections. It was concluded that the accumbens plays a primary role in mediating the rewarding effects of amphetamine and that the AP region plays a primary role in mediating the CTA. This constitutes an anatomical disassociation of amphetamine's rewarding and aversive effects. The differential associative bias of place-reward and taste-aversion learning apparent in the results is discussed. PMID- 3088662 TI - The effects of transdermal scopolamine and four dose levels of oral scopolamine (0.15, 0.3, 0.6, and 1.2 mg) upon psychological performance. AB - Four dose levels of oral scopolamine (0.15 mg, 0.3 mg, 0.6 mg, 1,2 mg), transdermal scopolamine, and placebo, were investigated for their effects upon a battery of psychological performance measures in normal subjects. Oral scopolamine produced significant linear dose-related decrements on tasks involving continuous attention, continuous performance, memory storage for new information, and on self-rated feelings of alertness and sociability. Transdermal scopolamine produced significant performance impairments on these same assessment measures. Resting heart rate levels were significantly reduced by all scopolamine conditions. Side effects (dry mouth, dizziness) were frequent following transdermal scopolamine and the higher oral dose conditions. The overall effects of the transdermal scopolamine patch were broadly equivalent to the effects of 0.8 mg oral scopolamine. This oral dose equivalence for transdermal scopolamine is higher than expected, and possible reasons for this are discussed. PMID- 3088663 TI - Reversal and nonreversal shifts under amphetamine. AB - Rats were trained in a Y maze on a two-choice simultaneous brightness discrimination with light as S+ and dark as S- (position irrelevant). Half of the animals were then switched to reversal, where the reinforcement contingencies of the original training were reversed, and the other half were switched to nonreversal, in which they learned a simultaneous right-left discrimination. Nonreversal was acquired faster than reversal in saline injected animals. The administration of 1 mg/kg d-amphetamine did not affect the acquisition of the initial brightness discrimination and of nonreversal. In contrast, the drug facilitated dramatically reversal learning. The results indicate that amphetamine enhances the attention to, or the associability of, the discriminative stimuli, leading to rapid learning to these stimuli under changed contingencies of reinforcement. PMID- 3088664 TI - Effects of repeated doses of fluvoxamine, mianserin and placebo on memory and measures of sedation. AB - The effects on memory and learning of fluvoxamine 50 mg twice a day were compared with those of mianserin 20 mg twice a day and placebo, each given for 8 days in a double-blind cross-over design to nine healthy human volunteers. At least 1 week was left between the 8-day courses of drugs. Subjects were given a learning task (three trial recall of categorisable word lists) before and 3.5 h after a morning dose on day 1 and before their morning dose on day 8. Delayed recall was assessed on days 1, 4 and 8. Fluvoxamine had no effect on memory performance. Mianserin reduced learning and recall after a single dose but had no effect on day 8 of treatment. The single dose of mianserin had no retrograde effect on memory, affected primacy and middle position items but not recency in the serial position curve, and was seen in reduced inter-trial subjective organisation of recall. Subjects' performance on the first trial of the memory task correlated significantly with their performance on a simple reaction time task, with finger tapping speeds and with their subjective ratings of alertness. It was concluded that the impairments of memory produced by one dose of mianserin are partially by products of the sedative effects of the drug. Tolerance to both memory impairments and sedative effects built up over the 8-day treatment of mianserin. PMID- 3088666 TI - The effect of pramiracetam (CI-879) on the acquisition of a radial arm maze task. AB - The effect of the nootropic drug pramiracetam (CI-879) on acquisition of a radial arm maze task was examined in the rat. Two doses of pramiracetam (7.5 mg/kg and 15 mg/kg) were administered daily prior to testing for 7 weeks in a 16-arm radial maze in which nine arms were baited with food. This procedure permitted a distinction between working memory (short-term) and reference memory (long-term). Both doses of pramiracetam significantly improved performance in the reference memory component of the task, but did not significantly affect the working memory component. These data indicate that pramiracetam can enhance some aspects of spatial learning and memory in the rat. PMID- 3088665 TI - Behavioral and biochemical studies of dopamine receptor sensitivity in differentially housed mice. AB - Group housed and individually housed mice were compared in (1) the motor activity responses to direct and indirect dopamine (DA) agonists, (2) in vivo presynaptic autoreceptor sensitivity and (3) in vitro binding of 3H-spiperone. Relative to group housed mice, individually housed mice showed an increased motor activity response to amphetamine, 1.25 and 0.625 mg/kg. Using two in vivo measures of presynaptic DA receptor sensitivity, the antagonism of spontaneous locomotor activity and the antagonism of dihydroxyphenylalanine (DOPA) accumulation by apomorphine (APO), individually housed mice showed greater activity counts and higher DOPA accumulations than group housed mice. Levels of tyrosine were significantly greater in individually housed mice. Significant effects of housing were also noted with the motor activity response to APO, 0.075-0.300 mg/kg, following pretreatment with reserpine, an in vivo measure of postsynaptic receptor sensitivity. However, there was no effect of housing on the number or affinity of 3H-spiperone binding sites in the striatum. These results are discussed in terms of the presynaptic activity of catecholaminergic neurons and the postsynaptic receptor sensitivity to APO in individually housed mice. PMID- 3088667 TI - Stereoselective analysis of racemic psychotropic compounds by HPLC on chiral stationary phase. PMID- 3088668 TI - Use of a standardized documentation system (BLIPS/BDP) in the conduct of a multicenter international trial comparing fluvoxamine, imipramine, and placebo. PMID- 3088669 TI - Enteric alimentation: a radiologic approach. AB - A new guide wire-directed enteric feeding tube is described. Clinical trials have shown the tube can be rapidly placed in the small bowel in patients with altered gastric anatomy or decreased peristalsis. Fluoroscopically guided feeding tube placement has proved to be a valuable adjunct in the therapy of patients requiring long-term enteric alimentation. PMID- 3088670 TI - Express saccades in man and monkey. PMID- 3088671 TI - The contribution of basal ganglia to limb control. PMID- 3088672 TI - Role of the central thalamus in gaze control. PMID- 3088673 TI - A comparison of disorders in saccades and in fast and accurate elbow flexions during cerebellar dysfunction. PMID- 3088675 TI - Time-dependent inhibition of platelet cyclooxygenase by indomethacin is slowly reversible. AB - Indomethacin has been characterized in vitro as a time-dependent, irreversible inhibitor of cyclo-oxygenase, yet its effects on human platelets have been found to be reversible in vivo. To understand this apparent contradiction, we have investigated the kinetics of recovery of platelet thromboxane production after a single dose of indomethacin. The inhibition of platelet thromboxane production was greater than would be expected from the levels of indomethacin found in the plasma suggesting that the time-dependent inhibition occurs in vivo. Yet recovery of platelet thromboxane production was faster than expected for an irreversible inhibitor, with 50% of control values being regained within 24 hours after ingestion of the drug. When platelets were isolated and resuspended in homologous drug-free plasma, slow recovery of thromboxane production was seen to occur with 50% of control activity regained in 100 minutes. This recovery was much slower than that seen from a competitive inhibitor of cyclo-oxygenase, ibuprofen. Ibuprofen-treated platelets recovered nearly completely immediately on being resuspended in drug-free plasma. When microsomes were isolated from platelets, then treated with indomethacin, no time-dependent recovery of activity was seen. The recovery of cyclo-oxygenase after indomethacin inhibition appears to be limited to the unperturbed enzyme in its natural milieu. PMID- 3088674 TI - Prostaglandin synthesis by enterocyte microsomes of rabbit small intestine. AB - We studied the prostaglandin (PG) synthetic capacity of microsomes of a relatively pure population of rabbit enterocytes and determined ideal conditions for product synthesis. The epithelial cells were freed from the basement membrane by a combination of calcium chelation and mechanical vibration, and 100,000 X g microsomes were prepared. These microsomes were found to synthesize PG from exogenously added arachidonic acid. The ideal conditions for the reaction were a microsomal protein concentration of 1.0 mg/ml, an arachidonic acid concentration of 33 uM, a reaction mixture pH of 8.0-9.5 and with epinephrine 1.5 mM added as a cofactor. The product yields increased linearly with time up to 30 min. of incubation and were inhibited by 100 uM indomethacin. Under the above ideal conditions enterocyte microsomes yielded the following products expressed as pmole/mg protein/20 min. incubation: PGF2 alpha 98 +/- 7, PGE2 48 +/- 9, PGD2 28 +/- 7, TxB2 40 +/- 5, 6 Keto PGF1 alpha 15 +/- 6. PMID- 3088677 TI - Inhibition of prostaglandin biosynthesis by SQ 28,852, a 7 oxabicyclo[2.2.1]heptane analog. AB - 7-Oxabicyclo[2.2.1]heptane analogs of prostaglandin (PG) H2 can act as thromboxane (Tx) A2 receptor antagonists or agonists, PGI2 and/or PGD2 receptor agonists, or exhibit a mixture of the above activities. SQ 28,852, a new analog with a hexyloxymethyl omega side chain, is a potent inhibitor of PG synthesis. SQ 28,852 inhibited collagen and arachidonic acid (AA)-induced platelet aggregation and TxB2 and PGE2 formation, but did not block platelet aggregation induced by ADP or the TxA2 mimics, 9,11-azo PGH2, SQ 26,655, and U-46,619. It also blocked conversion of AA to TxB2, PGE2, and 6-keto PGF1 alpha by microsomal preparations of human platelets, bovine seminal vesicles, and bovine aortas, respectively, but did not inhibit the conversion of PGH2 to TxA2 by the platelet microsomal preparation. SQ 28,852 (p.o.) protected mice against the lethal effects of AA (75 mg/kg, i.v.). The I50 values for SQ 28,852, indomethacin and aspirin were 0.025, 0.05 and 15 mg/kg, respectively. Neither SQ 28,852 nor indomethacin protected mice from death caused by 9,11-azo PGH2. SQ 28,852 (0.01 to 1 mg/kg, i.v.) inhibited AA-induced bronchoconstriction in anesthetized guinea pigs for at least 60 min. As an inhibitor of AA-induced bronchoconstriction, SQ 28,852 was 16- and 45-times more potent than indomethacin at 3 and 60 min after i.v. administration, respectively. SQ 28,852 did not inhibit bronchoconstriction induced by histamine or 9,11-azo PGH2, indicating its specificity of action in vivo. SQ 28,852 is the first example of a new class of cyclooxygenase inhibitors whose structure is similar to that of the naturally occurring endoperoxide, PGH2. PMID- 3088676 TI - Differential alteration of lipoxygenase and cyclooxygenase metabolism by rat peritoneal macrophages induced by endotoxin tolerance. AB - Altered macrophage arachidonic acid metabolism may play a role in endotoxic shock and the phenomenon of endotoxin tolerance induced by repeated injections of endotoxin. Studies were initiated to characterize both lipoxygenase and cyclooxygenase metabolite formation by endotoxin tolerant and non-tolerant macrophages in response to 4 different stimuli, i.e. endotoxin, glucan, zymosan, and the calcium ionophore A23187. In contrast to previous reports of decreased prostaglandin synthesis by tolerant macrophages, A23187-stimulated immunoreactive (i) leukotriene (LT)C4/D4 and prostaglandin (PG)E2 production by tolerant cells was greater than that by non-tolerant controls (p less than 0.001). However, A23187-stimulated i-6-keto-PGF1 alpha levels were lower in tolerant macrophages compared to controls. Stimulation of prostaglandin and thromboxane (Tx)B2 synthesis by endotoxin or glucan was significantly less in tolerant macrophages compared to controls (p less than 0.05). iLTC4/D4 production was not significantly stimulated by endotoxin or glucan, but was stimulated by zymosan in the non-tolerant cells. Synthesis of iLTB4 by control macrophages was stimulated by endotoxin (p less than 0.01). These results demonstrate that arachidonic acid metabolism via the lipoxygenase and cyclooxygenase pathways in macrophages is differentially altered by endotoxin tolerance. PMID- 3088678 TI - Metabolism of viprostol--a synthetic vasodilator PGE2 analog. AB - Metabolic studies were done with 14C-Viprostol (I) administered by various routes (I.V., oral and topical) to six animal species and to man. Total radioactivity and metabolic profiles were analyzed in plasma, tissues and excreta. The main metabolites were isolated and identified by capillary GC/MS. Plasma and urinary metabolic profiles were qualitatively similar across species, with two major metabolic reactions being predominant: rapid hydrolysis to the pharmacologically active free acid (II) and oxidation of the alpha-chain to dinor and tetranor acids (III, IV). In the monkey and man, reduction of the 9-keto group lead to PGF2 type metabolites (VI-VIII). In the rat, omega oxidation of the beta-chain occurred as well, resulting in the formation of dicarboxylic acids (V). PMID- 3088679 TI - Acetylcholine induces vasodilation and prostacyclin synthesis in rat lungs. AB - Acetylcholine causes pulmonary vasodilation, but its mechanism of action is unclear. We hypothesized that acetylcholine-induced pulmonary vasodilation might be associated with prostacyclin formation. Therefore, we used isolated rat lungs perfused with a recirculating cell- and plasma-free physiological salt solution to study the effect of acetylcholine infusion on pulmonary perfusion pressure, vascular responsiveness and lung prostacyclin production. Acetylcholine (20 micrograms infused over 1 minute) caused immediate vasodilation during ongoing hypoxic vasoconstriction and prolonged depression of subsequent hypoxic and angiotensin II-induced vasoconstrictions. Both effects of acetylcholine were abolished by atropine pretreatment. The prolonged acetylcholine effect, but not the immediate response, was blocked by meclofenamate, an inhibitor of cyclooxygenase. The prolonged effect, but not the immediate response, of acetylcholine was associated with an increase in perfusate 6-keto-PGF1 alpha concentration. The acetylcholine stimulated increase in 6-keto-PGF1 alpha production was inhibited by meclofenamate and by atropine. Thus, blockade of prostacyclin production corresponded with blockade of the prolonged acetylcholine effect. In conclusion, acetylcholine caused in isolated rat lungs an immediate vasodilation and a prolonged, time-dependent depression of vascular responsiveness. Whereas both acetylcholine effects were under muscarinic receptor control, only the prolonged effect depended on the cyclooxygenase pathway and, presumably, prostacyclin synthesis. PMID- 3088681 TI - Patterns of failure in nasopharyngeal cancer treated with megavoltage irradiation. AB - From 1976 to 1982, 78 patients with nasopharyngeal cancer (NPC) were treated with definitive megavoltage irradiation in accordance with a uniform protocol. The results of treatment were analyzed and prognostic factors reviewed. The incidence of primary failures was directly related to the extent of nasopharyngeal disease, since the relapse rate was 11% in T1T2 patients compared with 37.5% in T3T4 patients. Similarly, failure in the neck correlated with the N stage, being negligible for N0 and N1, while 35.7% for N3. The presence of bulky cervical nodes was associated with a higher risk for metastases: hematogenous dissemination occurred in 50% of N3B patients. The histology pattern seemed to significantly affect the ultimate outcome of patients with NPC, since disease free survival was 65.5% in patients with a diagnosis of undifferentiated carcinoma (UC) and 23.8% in patients with squamous cell carcinoma (SC). The major cause of poor survival in this latter patient group was not only a higher recurrence rate of both primary and nodal disease but a greater incidence of distant metastases as well. PMID- 3088680 TI - [Treatment of malignant melanoma]. PMID- 3088682 TI - Processing of the thyrotropin releasing hormone (TRH) precursor in Xenopus skin and bovine hypothalamus: evidence for the existence of extended forms of TRH. AB - Acid extracts of Xenopus laevis skin were fractionated by gel filtration on Sephadex G50 ion-exchange chromatography and reverse-phase high performance liquid chromatography (HPLC). Peptides related to thyrotropin releasing hormone (TRH) were identified in the eluted fractions by trypsin digestion and radioimmunoassay (RIA) using antibodies to the TRH tripeptide pGlu-His-Pro amide or to a TRH-related pentapeptide pGlu-His-Pro-Gly-Lys. In addition to the tripeptide hormone, evidence was obtained for the presence of peptides containing 10-20 amino acid residues which were extended on the NH2-terminal or COOH terminal side of TRH. The peptides extending on the NH2-terminal side predominated and were shown to comprise 5 components present in differing concentrations, indicating that the processing sites in the TRH prohormone vary in their susceptibility to proteolysis. Evidence was also obtained for the presence of small amounts of the TRH-related pentapeptide pGlu-His-Pro-Gly-Lys. Using similar procedures it was demonstrated that TRH extended peptides were present in bovine hypothalamus. In this species the peptides extended at the NH2 terminus of TRH occurred in similar concentrations to the peptides extended at the COOH-terminus. The results show that processing of the TRH prohormone in Xenopus and ox leads to the formation of peptides intermediate in size between the prohormone and the tripeptide amide; the TRH extended peptides occur in significant quantity and in Xenopus are formed with a high degree of specificity. PMID- 3088684 TI - [Calculation of direct standard costs in the evaluation of new technologies: application to the treatment of acute myeloblastic leukemias]. AB - Financial incidence of new technology can be approached through the utilization of "direct standard cost". This method allows actualization of prices and permits the integration of new procedures. It is applied to acute non lymphoblastic leukemia. PMID- 3088683 TI - [Meningococcal meningitis with antigens common to Neisseria meningitidis and Neisseria gonorrhoeae]. PMID- 3088685 TI - [Seizures recorded upon awakening in the child: diagnostic difficulties]. AB - We describe the EEG patterns and the clinical modifications of spontaneous awakening in 34 infants and children. An "awakening seizure" could be confirmed in 27 children, including 18 with various epilepsies and 9 infants with West syndrome. In other 7 children, the analysis of the tracing could not conclude whether or not the pathological awakening patterns were critical. The frequency of seizures occurring with awakening in various epileptic syndromes might be underestimated: it rated 18% in our series of 150 children with a recorded seizure in a two years period. Since the EEG patterns occurring with awakening have been poorly studied in epileptic children, it may be difficult to distinguish a pathological arousal from an "awakening seizure". PMID- 3088686 TI - [Clinical manifestations of the anticoagulant lupus factor. Apropos of 2 cases and review of the literature]. PMID- 3088687 TI - [Response of prolactin to the administration of TRH in male patients with alcoholic cirrhosis: 1. Its relation to ascites]. PMID- 3088688 TI - [Colostasis and parenteral nutrition]. PMID- 3088689 TI - [Biological diagnosis of Mycoplasma pneumoniae respiratory infections]. AB - Mycoplasma pneumoniae is a frequent causal agent of respiratory infections. A recent french survey was carried out on adults in hospital for an acute pneumonia which was acquired outside hospital. This study showed Mycoplasma pneumoniae in third position, behind the pneumococcus and Legionella pneumophila, accounting for 17% of those cases with an established aetiology. Nevertheless its exact importance is difficult to establish on account of the high frequency of very benign forms in which a clinical diagnosis is not achieved. M. pneumoniae pneumonia occurs particularly in young subjects without any seasonal or geographical predominance. The infection is endemic with little epidemic peaks every four to five years. It is weakly contagious and is limited to close contacts. The laboratory diagnosis of M. pneumoniae pneumonia can be made by isolating the germ responsible or by a serological examination. Isolation is rarely performed. It is lengthy and difficult and may be obtained from sputum or better from throat swabs. Several serological examinations have been performed. The presence of cold agglutinins is non specific. A search for anti M. pneumoniae antibodies is much more helpful. It is done by complement fixation in most laboratories. The diagnosis of a M. pneumoniae infection can be confirmed by a significant change in antibody level between the first and second blood specimens 15 days apart (at least a four fold rise in the antibody level) if the first specimen was taken at the beginning of the illness. If a single serum specimen is examined a minimum titre of 1/64 may be taken as a presumptive diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3088690 TI - [Effect of aspirin and nordihydroguaiaretic acid on the secretion of milk caseins by the mammary epithelial cell]. AB - Phospholipase A2 and arachidonic acid mimic the stimulatory effect of prolactin on casein exocytosis. We suggest that prolactin by activating phospholipase A2, induces a release of arachidonic acid which is metabolized by a cyclooxygenase pathway leading to prostaglandins, prostacyclins and thromboxanes, a lipoxygenase pathway leading to hydroperoxides and leukotrienes and an epoxygenase pathway. The effects of prolactin and of the major products of arachidonic acid metabolism were studied by incubating mammary gland fragments of lactating rabbit and by measuring neosynthesized caseins and prostaglandins F (PGF2 alpha) in the incubation medium. Aspirin (10(-3) M) which strongly decreases PGF2 alpha synthesis did not modify exocytosis or prolactin stimulation of exocytosis. However, in some cases where prolactin did not stimulate exocytosis, aspirin could restore this stimulation. Nor-dihydroguaiaretic acid (10 microM), an inhibitor of lipoxygenases, increased PGF2 alpha synthesis in the presence of prolactin. In parallel, this inhibitor increased casein exocytosis but inhibited prolactin stimulation. These results are consistent with the action of arachidonic acid metabolites in the regulation of casein exocytosis. We suggest a dual control by the metabolites of the lipoxygenase and the cyclooxygenase pathways. PMID- 3088692 TI - Anatomical approaches to the study of neuropeptides and related mRNA in the central nervous system. PMID- 3088691 TI - [Development of the digestive function: regulation of the maturation of intestinal brush border enzymes]. AB - During the suckling period in mammals, the immaturity of the digestive function as well as several functional pecularities lead the gastrointestinal physiology to adapt to milk digestion and absorption. The dietary transition which occurs at weaning is accompanied by wide modifications as neonatal properties are lost and mature digestive functions are acquired. The involvement of factors like tissue interaction, hormones and nutritional substrates in the onset and subsequent maturation of intestinal brush border hydrolases is discussed. PMID- 3088693 TI - Prescribed daily dose of phenoxymethylpenicillin in general practice. AB - Prescribed daily dose (PDD) of phenoxymethylpenicillin was estimated in a multipractice study in 1979 and in 1983. PDD increased from 2.08 mio IU in 1979 to 2.32 mio IU in 1983. PDD was independent of number of daily doses, and factors related to practice. Only slight variations with diagnosis and doctor's age was found. PMID- 3088695 TI - [Total cystectomy. Special aspects. The parenteral nutrition pouch]. PMID- 3088694 TI - Microbiology of vaginal discharge in general practice. AB - Three groups of women were examined by culture for Gardnerella vaginalis and Candida. Group I consisted of 427 women, who complained spontaneously of vaginal discharge, group II of 311 women who did not complain of vaginal discharge until questioned prior to gynaecological examination, and group III of 100 women who denied vaginal discharge. Groups I and II also had cultures made for Trichomonas vaginalis and Neisseria gonorrhoica. In group I with spontaneous complaints the one-year prevalence rate of vaginal discharge was 3.4%. Candida, Trichomonas vaginalis and Neisseria gonorrhoica were cultured in 24%, 8% and 1% respectively. Gardnerella vaginalis was cultured in half of the women in all groups. A characteristic discharge or a positive microscopic finding was related to high concentration of Gardnerella vaginalis. A characteristic discharge even without spontaneous complaints of vaginal discharge was related to a high prevalence of Gardnerella vaginalis. Women complaining from discharge had higher concentrations of Gardnerella vaginalis than non-complaining. This leads to the conclusion that clinical disease may not be present unless concentrations of Gardnerella vaginalis have risen above some minimum level. The Gardnerella vaginalis syndrome defined by positive culture, clinical finding and microscopy was found in 20% of symptomatic women. PMID- 3088696 TI - [Management of diabetes mellitus in the child. Presented by the Workshop of Swiss Pediatric Diabetologists]. PMID- 3088697 TI - [Grand mal seizures and status epilepticus in general practice-- what's to be done?]. PMID- 3088698 TI - [Clinical treatment of grand mal epileptic status in adults]. PMID- 3088699 TI - [Status of minor (in a broad sense) epileptic seizures]. PMID- 3088700 TI - [Treatment of amyotrophic lateral sclerosis with thyrotropin releasing hormone]. AB - Nine patients (7 with amyotrophic lateral sclerosis, 1 with progressive spinal amyotrophy and 1 with chronic anterior poliomyelitis) were treated by sequential intravenous administration of 240 mg of TRH over one hour every two weeks. Results were assessed by an analytical evaluation of muscle strength before and 24 h after each infusion and by objective and subjective evaluation of spasticity. Significant improvement, as shown by statistical analysis, was noted in muscle strength in the 9 patients by 5 infusions over a 4-week period and a sub-group of 5 patients treated by 8 infusions over 10 weeks. Continued use of this therapy is justified by the need to determine its long-term effects and the psychological improvement noted in some patients after an even transient improvement in motor performance. However this treatment is obviously not curative. PMID- 3088701 TI - Tuberculosis of the middle ear: review of the literature with an instructive case report. AB - Tuberculosis of the middle ear is currently a rare disease in developed countries but one that still occurs and typically causes significant morbidity manifested by profound and permanent hearing loss. Diagnosis is difficult since most physicians are unfamiliar with the typical presenting features; in addition, special cultural and pathologic studies are required for diagnosis. A case report and review of the literature are presented to delineate typical clinical, epidemiologic, and laboratory features of tuberculous otitis media and associated tuberculous disease. A diagnostic and therapeutic plan is outlined that would allow early therapy and preservation of hearing. PMID- 3088702 TI - New ways of managing under prospective payment and their impact on the principles and practice of infectious diseases. AB - Medicare's Prospective Payment System (PPS) and its Diagnostic Related Groups (DRG) have celebrated a second anniversary. There is little doubt that the momentum of change started by the prospective payment concept will be around for some time. The formula for success contains a new approach to the management of health care organizations, instilling new life into health care management, creating challenges of new relationships and roles for medical staff, and serving to reshape the organizational structure of health care providers. Medicare will not be the only benefactor of this new scheme as prepayment spreads to other payors and providers of health care. Health care organizations have an opportunity to be innovative. Success will depend on whether health care executives and physicians can change, whether the results are satisfactory to users and payors, and whether the right incentives are preserved. The practice of infectious disease can play a unique and beneficial role in the prevention and control of infections through cost-effective surveillance programs and in the development and management of the antibiotics formulary. The costs of care can be appropriately controlled under the fixed payment systems, and survival in the new environment, more assured. PMID- 3088703 TI - [Acute bronchiolitis. Its diagnosis and treatment]. PMID- 3088704 TI - [Urinary infection in children (aspects of its etiopathogenesis, diagnosis, prognosis and treatment)]. PMID- 3088706 TI - [Implications of nutritional factors in the delayed growth of infants with congenital cardiopathies]. PMID- 3088705 TI - [Bioimmunological and morphoenzymatic correlations in protein-calorie malnutrition in infants]. PMID- 3088707 TI - [Genital tumors in children]. PMID- 3088708 TI - [Case of calcifying arteriopathy in an infant]. PMID- 3088709 TI - [Gluvilact o--a new preparation. A drug product]. PMID- 3088710 TI - [Aerosol therapy by intermittent positive pressure ventilation]. PMID- 3088711 TI - [Test of Materna o milk supplemented with iron in the feeding of premature infants]. PMID- 3088712 TI - [Use of artificial nutrition in 231 surgical patients]. PMID- 3088713 TI - [Results of determining polychlorinated biphenyl residue levels in the edible parts of fishes from the southern Baltic Sea and in fish products]. PMID- 3088714 TI - [Heart and heart-lung transplantation]. PMID- 3088715 TI - The basic apolipoprotein A-I in the patients with familial lecithin:cholesterol acyltransferase deficiency. AB - The apolipoprotein A-I (apo A-I) from the patients with familial lecithin: cholesterol acyltransferase (LCAT) deficiency has been characterized. More than 10% of total serum apo A-I was recovered in the bottom fraction (d greater than 1.21 g/ml) of the patients' sera, while in normal sera, only 4.3 +/- 2.7% (Mean +/- SD) of apo A-I was found in the bottom fraction. The lipoproteins of the sera from the patients were analysed by density gradient ultracentrifugation and by high performance liquid chromatography (HPLC). Our HPLC analysis has revealed that the association of apo A-I with a lipid-poor HDL, observed in the patients, is not due to ultracentrifugal artifacts. The serum apo A-I isoproteins and their relative concentrations in the three patients were analysed by two dimensional electrophoresis. The isoprotein distribution for each of the three patients was as follows: isoproteins 2 and 3; 12.3, 21.2 and 25.7%, suggesting that the basic isoforms (isoproteins 2 and 3) were increased compared to normal controls (3.5 + 2.3%). The profile of apo A-I isoproteins of the bottom fraction was almost the same as that of the patient's HDL, indicating the equivalent affinity of each isoprotein with lipid and/or protein of HDL. These observations are compatible with the suggestion that the reduction of HDL-cholesterol in familial LCAT deficiency may be due to rapid catabolism of HDL, resulting in the increase in the ratio of apo A-I isoprotein 2 and 3 (immature form of isoprotein A-I) to isoprotein 4 and 5 (mature form of apo A-I). PMID- 3088716 TI - On-line computer evaluation of dye indicator dilution curves for determinations of capillary diffusion capacities. AB - A colourimetric indicator diffusion method has been modified to obtain more rapid and less elaborate estimations of the permeability surface area product (PS). The venous light absorbance curves of an intravascular reference substance and a permeable tracer substance are collected by a computer, which immediately presents the concentration curves versus time. Collected data are saved on diskettes. The data are normalized with respect to calibration and fractional as well as integrated capillary extraction values are presented. Extraction values can then be freely chosen for calculations of PS. The program is designed to give maximum precision and safety in the handling of calibrations and collected data. Albumin, labelled with cardiogreen, is used as reference dye and CrEDTA (MW = 341) or cyanocobalamine (vitamin B12, MW = 1355) as tracer. All dyes showed linearity between concentration and densitometer output in the concentration interval used. Both spatial and temporal accuracy of colourimetric recordings are superior to radioactivity measurements. However, the technique is so far limited to the use of cell-free perfusates. PMID- 3088717 TI - Determination of 51Cr-EDTA clearance in infants by a single capillary blood sample. AB - A method by which 51Cr-EDTA plasma clearance is determined from a single capillary blood sample (Clsc) was studied in 52 children less than 1 year old. The Clsc is calculated as the ratio between the injected dose and the total area under a transformed monoexponential function. The monoexponential curve is determined from the plasma activity 120 min after i.v. single injection of 51Cr EDTA and a hypothetical initial activity calculated as the injected dose divided by the distribution space of 51Cr-EDTA. The distribution space was estimated from the body surface area. The rate constant of the monoexponential function is transformed by an empirically determined factor to make the area under the curve identical to the area under the true plasma disappearance curve. The Clsc was compared with 51Cr-EDTA plasma clearance (range 18-146 ml/min/1.73 m2) determined by a standard method from five capillary blood samples (Cl). The regression of Cl on Clsc did not differ from the line of identity, the SD being 5.9 ml/min/1.73 m2. In advanced renal failure the one-sample method is very sensitive to inaccuracies in the distribution space estimate and, accordingly, this method should be used only when the clearance value is predicted higher than 30 ml/min/1.73 m2. PMID- 3088718 TI - Drug- and temperature-induced changes in peripheral circulation measured by laser Doppler flowmetry and digital-pulse plethysmography. AB - We measured the effects of a new transdermal nitroglycerin patch (25 mg, 10 cm2) applied for 24 h, norphenephrine (6 mg), prazosin (1 mg) as well as local heat and cold provocation on blood pressure, heart rate, skin blood flow (measured by laser-Doppler flowmetry, L-D) and peripheral arterial resistance (assessed by digital pulse plethysmography, D-P) in 15 healthy volunteers (aged 21-31 years). Heat provocation induced a three-fold increase in skin blood flow in the hand (p less than 0.001) and cold provocation a decrease in flow (p less than 0.05) of about 20%. Forehead skin blood flow did not change. Peripheral arterial resistance showed less consistent changes during the provocation tests. Prazosin increased the forehead skin blood flow (p less than 0.01) and decreased peripheral arterial resistance, while norphenephrine showed an opposite effect. Transdermal nitroglycerin induced an increase of 25% in forehead skin blood flow (p less than 0.05) which persisted for 24 h and a decrease in peripheral arterial resistance (p less than 0.02), but this effect was evident up to 8 h only. We conclude that (1) local heat and cold provocation mainly affected skin blood flow, (2) vasodilative and vasoconstrictive drugs showed marked changes in peripheral arterial resistance, but at different points in time from subject to subject, and (3) transdermal nitroglycerin patches induced haemodynamic changes persisting for up to 8-24 h. PMID- 3088719 TI - Effect of total parenteral nutrition on the zinc, copper, and manganese status of patients with catabolic disease. AB - The zinc, copper, and manganese concentrations in liver and muscle and the serum zinc were measured in 24 malnourished patients before and after 10-12 days' parenteral nutrition with 3 different alimentation programs. The nutrition programs contained similar trace element substitutions. Malnutrition caused by different catabolic diseases resulted in an increase of zinc and copper contents in the liver and a rise of serum zinc in many patients and in a decrease of muscle zinc concentration in certain patients. Parenteral nutrition of any kind resulted in a decrease of liver zinc and copper content and of serum zinc, yielding subnormal zinc values in 25-58% of the patients in spite of a daily substitution of 1.9 mg zinc. There was no significant change in the manganese status because of malnutrition or parenteral alimentation. It is concluded that the serum zinc concentration does not show the real zinc status of the body in the patients with catabolism, that in certain catabolic diseases zinc and copper are redistributed to the liver, that certain catabolic diseases cause a zinc depletion of the muscle, that parenteral nutrition results in a fall of zinc and copper in the liver and in a decrease of serum zinc, which may be harmful from the healing point of view, and that the daily substitution of zinc used in this study, 1.9 mg/day, is not sufficient during parenteral nutrition of catabolic patients. PMID- 3088720 TI - Catheter-related septicaemia in patients receiving home parenteral nutrition. AB - Forty-three patients received home parenteral nutrition (HPN) for 4 to 13 months (median, 30 months) with a total treatment period of 153 patient-years. All patients had central venous catheters; 71 PVC subclavian catheters, 138 Broviac catheters, and 16 other catheters were used. Broviac catheters were introduced into the central veins via a tunnel on the chest (94 catheters) or on the thigh (44 catheters). Eighty-two episodes of catheter septicaemia occurred in 28 (65%) of the patients, corresponding to an incidence of catheter septicaemia of 1 in 1.9 patient-years. The commonest microorganisms grown from the blood were coagulase-negative staphylococci, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Candida species. Septicaemia incidence was 1 in 2.6 catheter-years with the Broviac catheter on the chest and 1 in 1.6 catheter-years with the Broviac catheter on the thigh. In 49 cases the patient was treated with both antibiotics and change of the catheters, in 26 cases with antibiotics alone, and in 5 cases with change of the catheter alone. The antibiotic therapy was given for 3 to 15 days (median, 7 days). No patient died of catheter septicaemia. The relapse rate was low (less than 10%) and did not differ significantly between the three treatment groups. It is concluded that catheter septicaemia is a common complication of HPN. In most cases it runs a mild course. Bacteriaemia can often be eradicated by a brief antibiotic therapy without catheter exchange. PMID- 3088721 TI - Synergistic action of gamma interferon and catalase to reverse the suppressive effect of peritoneal macrophages on concanavalin A-induced lymphocyte proliferation. AB - The suppressive effect of normal rat peritoneal exudate cells (PEC) on concanavalin A (Con-A)-induced lymphocyte proliferation was studied. Partial suppression of proliferation was obtained by adding 3% PEC and complete suppression was observed with 6% PEC. The suppressive effect was mediated by W3/25+ plastic-adherent macrophages, which constitute about 60% of normal PEC. Addition of PEC prior to, simultaneously with, or 24 h after, but not 48 h after, the stimulation of lymphocytes with Con A resulted in suppression. Suppressed cultures produced normal or slightly increased amounts of interleukin 2 (IL-2), but the expression of the IL-2 receptor on lymphocytes was decreased. Pre exposure of PEC to gamma interferon (IFN-gamma) resulted in decreased suppression, whereas IFN-gamma added simultaneously with the lymphocytes had no effect. Catalase reversed PEC-induced suppression and significant synergistic effects were recorded when combined with IFN-gamma. Even completely suppressed cultures were effectively protected from suppression. Indomethacin and combinations of indomethacin with catalase or IFN-gamma did not result in additional protection from PEC-mediated suppression. PMID- 3088722 TI - Regulation of natural killer cytotoxicity by Escherichia coli-derived human interferon gamma. AB - The abilities of Escherichia coli-derived human interferon gamma (IFN-gamma) and E. coli-derived human interferon-alpha A (IFN-alpha A) or -alpha 2 (IFN-alpha 2) to augment natural killer (NK) cytotoxicity were compared. When low concentrations (less than 10 antiviral units/ml) of interferons were used, and equal numbers of antiviral units of E. coli-derived IFN-gamma and E. coli-derived IFN-alpha A or IFN-alpha 2 were compared for their ability to augment NK, E. coli derived IFN-gamma was found to be more active in augmenting NK against the K562 targets, than E. coli-derived IFN-alpha A or IFN-alpha 2. Antiviral units in these experiments were determined by the standard cytopathic effect assay using vesicular stomatitis virus (VSV)-challenged human fibroblasts, trisomic for chromosome 21. However, when these interferons were compared on a weight basis (ng/ml) or on a molar basis, their ability to augment NK against the K562 targets was comparable. These differences in the relative abilities of these interferons (when their concentrations were expressed in antiviral units/ml) to augment NK, were due to an approximately 100-fold difference in their specific activities (antiviral units per mg of interferon). These were 1.8 X 10(6) units/mg for E. coli-derived IFN-gamma, 2.0 X 10(8) units/mg for E. coli-derived IFN-alpha A, and 1.8 X 10(8) units/mg for E. coli-derived IFN-alpha 2. At concentrations higher than 10 units/ml, all these interferons showed a similar ability to augment NK. Studies on the kinetics of the augmentation revealed that in vitro treatment with E. coli-derived IFN-gamma for several hours was necessary for augmentation of NK against targets from haemopoietic human tumour cell lines (K562, Daudi). In contrast, alpha interferons were able to augment NK after treatment in vitro for significantly shorter periods (30 min or less with certain donors). Augmentation of NK cytotoxicity of human peripheral blood mononuclear leucocytes by E. coli derived IFN-gamma was not accompanied by the induction of interleukin 2 (IL-2) production, suggesting that IL-2 is not involved in the augmentation of NK by IFN gamma. A monoclonal antibody specific for human IFN-gamma blocked augmentation of NK by E. coli-derived IFN-gamma and natural IFN-gamma, but not by E. coli-derived IFN-alpha A or staphylococcal enterotoxin A (SEA).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3088723 TI - [Evaluation of scintigraphic procedures for clarifying pain conditions in hip joint prostheses]. AB - 59 patients with implanted one- or two-sided hip prostheses (n = 74) have been investigated by two different scanning techniques to detect both possible loosening of the prostheses and a possible infection as the cause of the loosening. Of the investigated prostheses 47 were loose; in 45 cases this was evidenced by the bone scan using Tc-99m-DPD, thus showing a sensitivity of 95%. Specificity was 89%. In 21 cases (45%) of loose prostheses an infection could be clinically proven. With the aid of In-111 labeled leukocyte scans, 17 of 21 cases were correctly diagnosed as infected, showing a sensitivity of 91%, while the specificity was 94%. In view of the 93% accuracy, bone scanning can be regarded as the method of choice in detecting loosening of prostheses. The 91% accuracy in proving or ruling out infection by means of the leukocyte scan is high enough to assert correct findings in most cases. The main disadvantage of this method is the very demanding technique for marking of white blood cells. PMID- 3088724 TI - New blood test raises thorny issues. PMID- 3088725 TI - NIH transfers disputed monkeys to Regional Primate Center. PMID- 3088726 TI - Molecular biology of Homo sapiens. PMID- 3088727 TI - Study of aldose reductase inhibition in intact lenses by 13C nuclear magnetic resonance spectroscopy. AB - Carbon-13 nuclear magnetic resonance spectroscopy has been used in the study of glucose metabolism, specifically aldose reductase inhibition, in intact rabbit lenses maintained in organ culture. This technique provides an effective method of screening potential inhibitors of aldose reductase under conditions that more closely approximate in vivo conditions than do earlier methods. The aspirin substitutes acetaminophen and ibuprofen were studied as aldose reductase inhibitors and were found to be effective in reducing sorbitol accumulation in lenses exposed to high glucose stress. Results of this work with various inhibitors of aldose reductase are discussed in terms of lens metabolism and implications regarding diabetic complications such as cataract formation. PMID- 3088728 TI - Studies on environmental chemical carcinogenesis in Japan. AB - The historical background of studies in Japan on chemical carcinogenesis from environmental sources is described from personal experience. PMID- 3088729 TI - Regulation of expression of the interleukin-2 receptor on hematopoietic cells by interleukin-3. AB - Remarkable similarities in the intracellular and genetic events occur when lymphoid and hematopoietic cells are exposed to their specific growth factors. The interleukin-2 (IL-2) receptor, whose cell-surface expression is an absolute requirement for the growth and differentiation of lymphoid cells, was detected on various nonlymphoid hematopoietic cell types in this study. Cell lines consisting either of granulocyte-macrophage precursors or mast cells, which are dependent on interleukin-3 (IL-3) for their growth, expressed high levels of the IL-2 receptor on their surface. Analysis of the binding characteristics of these receptors with 125I-labeled recombinant IL-2 revealed that only receptors with low affinity for IL-2 were present on these cells. Addition of purified recombinant IL-3 to these cell lines led to an increase in IL-2 receptor gene expression within 1 hour in isolated nuclei. This IL-3--induced increase in the number of IL-2 receptors on the cell surface is maximal within 24 hours. Addition of 10,000 units of IL-2 to these cells had no apparent effect on their growth or differentiation. The presence of the receptor with only low affinity for IL-2 on hematopoietic cells and the regulation by IL-3 suggest that this receptor is involved in some important metabolic event in hematopoiesis. PMID- 3088730 TI - Extrinsic displacement of the ureter. PMID- 3088731 TI - Heterophilic antibody as a source of error in immunoassay. AB - We describe our experience with a young woman believed to be hypothyroid and menopausal because of erroneously elevated TSH, LH, and FSH estimates. These errors were found to be due to the presence of antibodies to rabbit IgG in the patient's blood. We found that antibody-limited assays for TSH, LH, and FSH using antisera raised in rabbits were affected by this problem unless rabbit IgG was included, whereas antibody-excess assays were not. These problems were most simply detected by observing inappropriate results when measurements were made in dilutions of the patient's serum. The presence of endogenous antibody directed against antibodies used in immunoassays is a significant potential source of error requiring awareness on the part of both the clinician caring for such patients and the clinical laboratory making the measurements. PMID- 3088732 TI - [Rehabilitation of the malnourished patient]. PMID- 3088733 TI - [Nursing care of the malnourished patient. Technics in artificial nutrition]. PMID- 3088734 TI - [Malnutrition]. PMID- 3088736 TI - [Ways of reducing the toxicity of chemotherapy of cancer of the ovaries]. PMID- 3088735 TI - [Anesthesia in the malnourished patient]. PMID- 3088737 TI - [Acute biliary surgery]. PMID- 3088738 TI - [Noxyflex S in the prevention and therapy of intra-abdominal inflammatory complications]. PMID- 3088739 TI - Effects of single doses of two antihypertensive rauwolfia-diuretic combinations on urinary excretion. AB - In a double-blind placebo-controlled investigation, 14 healthy adult male volunteers were studied to assess and compare the urinary effects of acute single doses of two antihypertensive formulations containing: hydroflumethiazide 50 mg, Rauwolfia serpentina 50 mg and potassium chloride 625 mg (HFRK) (Rautrax-50; Squibb Laboratories); and clopamide 5 mg, reserpine 0.1 mg and dihydroergocristine 0.5 mg (CRE) (Brinerdin; Sandoz Products). Both significantly increased mean 24-hour urinary outputs of fluid, Cl-, Na+, K+ and Mg2+. CRE increased creatinine and decreased Ca2+ output. After dosing, times to maximal urinary flow of fluid, Cl-, Na+, Ca2+ and creatinine were shortened by HFRK and CRE and those corresponding to K+, Mg2+, phosphate and urate were unaffected. Both formulations thus acted mainly through their diuretic constituents. PMID- 3088740 TI - [Diabetic ketoacidosis and hypofibrinogenemia as a complication of the treatment with L-asparaginase of acute lymphoblastic leukemia]. PMID- 3088741 TI - Parenteral nutrition of injured patients. AB - Injured patients treated with fructose 1,6-diphosphate (1 millimole of phosphate per kilogram per day) together with parenteral nutrition had a better nitrogen balance than patients treated with isocaloric nutrition and an inorganic source of phosphate. Excretion of 3-methylhystidine was similar while tyrosine and alanine output from the extremities was lower in the group of patients given fructose 1,6-diphosphate. The data indicates that the protein sparing action of fructose 1,6-diphosphate is exerted through an increased protein synthesis. PMID- 3088742 TI - Morphology and functional anatomy of the first dorsal interosseous muscle of the hand. AB - The aim of this study, based upon anatomical and electrophysiological evaluation, was to identify the relationship between the morphology and physiology of the first dorsal interosseous muscle of the hand, which should be distinguished from the other dorsal interosseous muscles of the hand. Its morphology, distal attachments and physiology have been subject of numerous studies yielding conflicting results. The study reported herein was made on the basis of anatomical and electrophysiological investigation. Most of the dissections (20/34) were made on fresh specimens. Results of this study confirm the existence of the deep and superficial heads of the 1st dorsal interosseous muscle. The muscle is attached distally to the palmar plate of the metacarpophalangeal joint, the lateral tubercle of the base of the proximal phalanx of the index and the interosseous hood. Conversely, the muscle did not show any attachment to the oblique radial wing of the extensor apparatus in our dissections. The deep head of the muscle causes mainly flexion pinch between thumb and index superficial head abduction. Within the complex physiology of the various types of apposition of thumb and index, the dorsal interosseous muscle acts as a stabilizer. The results of electrophysiological study confirmed most of the interpretations deduced from morphological investigation. PMID- 3088743 TI - Study of the experimental biomechanics of tendon repair with immediate active mobilization. AB - The authors present a biomechanical study of tendon behavior after primary suturing and early active mobilization. In this animal study (23 specimens), three types of sutures are compared using 2 biomechanical parameters: the load at rupture (R), and Young's modulus of elasticity (E). The authors show that early mobilization does not compromise the final strength of a tendon. Moreover, early mobilization confers the biomechanical characteristics of resistance and elasticity more closely akin to those of the normal tendon. Pathoanatomical examinations confirm the fibroelastic reaction of cicatrization and the mechanical role of mobilization in the orientation of newly formed tendon fibers. PMID- 3088745 TI - From classical to modern anatomy or computer-assisted biomechanics. AB - The authors describe their methodology - dissection, photography, informational - permitting a biomechanical approach together with the study of the changes in the topographic anatomy of a region during movement. PMID- 3088744 TI - The three-dimensional active rotary stabilization of the knee. AB - The careful examination of insertions and directions of the tendons of the knee peri-articular muscles permits a global conception of the action of the 29 couples in rotatory stabilization. First, an analytic study of the tibial and femoral rotatory stabilization is considered. Second, the three-dimensional rotatory mechanical coupling between femur and tibia is developed. The anatomical complexity of the musculotendinous elements allows understanding of the risks of desynchronisation of the articular joint in case of lesion of the central ligament pivot. PMID- 3088746 TI - Magnetic resonance imaging of the brainstem and cranial nerves. AB - Ten normal human volunteers and 44 patients with pathology of the brainstem or cranial nerves were scanned using a. 3 Tesla permanent MR imaging system. MR images were obtained of the cranial nerves and brainstem using various spin-echo pulse sequences and scanning planes. 4 mm thick sections with .75 mm pixels on a 256 display matrix were used whenever possible. The normal MR images were correlated with thin section cryodissection specimens of fresh human cadavers. Brainstem structures including major nuclei and tracts were then identified. The cranial nerves were followed through the subarachnoid cisterns and the base of the skull. Pathological involvement of the brainstem by tumors, infarcts, and demyelinating disease was well shown and correlated with clinical findings. Examples of optic glioma, fifth, eighth, and twelfth nerve schwannomas as well as other cranial nerve pathology were also demonstrated. Magnetic resonance produces excellent images of cranial nerves and brainstem with high contrast resolution. Unlike CT, there is no beam hardening artifact from bone. T1 weighted images maximize brainstem-CSF contrast and are useful for demonstrating the external anatomy of the brainstem and cranial nerves. The T2 weighted images show internal brainstem anatomy, CSF within neural foramina, and highlight many pathological conditions. PMID- 3088747 TI - The mandibulo-stylohyoid ligament. AB - The mandibulo-stylohyoid ligament was studied in both sides of five cadavers, the surgical importance of the structure is confirmed and the anatomical importance as a landmark is emphasized. PMID- 3088748 TI - Anatomical bases for surgical approach to the initial segment of the anterior cerebral artery. Microanatomy of Heubner's artery and perforating branches of the anterior cerebral artery. AB - Both the Heubner's artery and the perforating branches of the anterior cerebral artery (ACA) were present in all thirty-three examined brains. Heubner's arteries varied in number from 1 to 3. They originated from the distal (A2) segment of the ACA in 34% of the cases, from the proximal (A1) segment of the ACA in 17%, at the level of the anterior communicating artery in 21%, from the fenestration of the ACA in 8%, and in all the other cases (20%) from the azygous anterior cerebral artery, accessory middle cerebral artery, frontopolar artery and, finally, by the common stem with the medial orbitofrontal artery. Heubner's artery most commonly terminated dorsal and lateral to the carotid bifurcation, at an average distance of 4.8 mm. The mean diameter of Heubner's artery was 662 microns, that of its extracerebral collateral branches 205 microns, of the terminal branches 462 microns, and of the intracerebral segments 354 microns. Perforating branches varied in number from 1 to 12 with an average of 6.6. The majority of the branches originated from the initial 6.1 mm of the A1 segment. These vessels terminated close to the carotid bifurcation, at an average distance of 3.8 mm. All the perforating branches were divided into small (average 122 microns in diameter) and large (average 325 microns). The mean diameter of intracerebral segments was 276 microns, and that of terminal branches 259 microns. It was concluded that the anatomical characteristics of both the recurrent artery and the perforating branches can be of a great significance in cerebrovascular diseases. PMID- 3088749 TI - Muscular attachments along the medial border of the scapula. AB - The authors described in this report the mode of attachments of muscles along the medial border of the scapula, as seen in sixty adult Indians. The levator scapulae, rhomboideus major and minor muscles comprise of double folds at the scapular end. The posterior folds of the levator scapulae and the rhomboideus minor muscles were attached to the dorsal surface of the medial border of the bone opposite the supraspinous fossa and the root of the spine respectively, while their anterior flaps gained attachment on the costal surface of the border at the level of the root of the scapular spine. The latter muscle reached much lower than the former. The rhomboideus major muscle was attached on the medial border of the scapula opposite the infraspinous fossa and could be traced to the dorsal surface of the bone just above the inferior angle. All the three muscles overlapped the costal surface of the serratus anterior fascia for about three centimeters. The fasciae of the muscles merged with each other along a straight line joining the free margins of their costal flaps. The serratus anterior muscle surrounds the superior and inferior angles of the scapula and is thus attached to both the surfaces of the bone at these sites. PMID- 3088750 TI - A note on the anastomoses between the hypoglossal nerve and the cervical plexus. AB - A series of 80 dissections was performed to define the anastomoses between the cervical plexus and the hypoglossal nerve (XII), the superior anastomosis between the trunk of XII and the ansa of the atlas from the cervical plexus; the ansa cervicalis, traditionally known as the ansa of the XIIth cranial nerve or hypoglossal ansa, formed by the direct junctional anastomosis of the descending branch of XII and the internal descending branch of the cervical plexus. The origins, form, branches and chief relations are defined in in the present study. PMID- 3088751 TI - A comparison of parenteral nutrition and early postoperative enteral feeding on the nitrogen balance after major surgery. AB - The nitrogen balance in 28 patients undergoing aortic grafting for aneurysm or occlusive disease was studied. Patients were randomized to receive after surgery either standard intravenous fluids (group 1), parenteral nutrition (group 2), or early postoperative enteral feeding (group 3). The mean daily negative nitrogen balance was 11.22 gm in group 1, 4.20 gm in group 2, and 4.14 gm in group 3. The difference between group 1 and groups 2 and 3 was highly significant (p less than 0.001), but there was no significant difference between groups 2 and 3. It is concluded that early postoperative enteral feeding can be as effective as parenteral nutrition in reducing the negative nitrogen balance induced by major surgery. PMID- 3088752 TI - Proximal alveolar bone loss in a longitudinal radiographic investigation. AB - The progression of proximal alveolar bone loss (ABD index) in an unselected material comprising 406 individuals was analysed by a longitudinal investigation over a period of ten years. In order to minimize the number of measurements and the drop-out of measurements of the difference in alveolar bone height between the two examinations a partial recording system was constructed. A partial index including five sites (12 m, 11 m, 33 d, 31 d, 41 m) gave high correlation to a total recording (r = 0.96). The best alternative in periapical radiographs to measuring the alveolar bone height in relation to the root length was to measure it in relation to the tooth length. This second method does not necessitate identification of the cemento-enamel junction. The mean alveolar bone difference was 5.5 per cent of the mean root length, which corresponds to an average bone loss of 0.09 mm per year. Eighteen variables were analysed as predictors in stepwise multiple regression analyses. The dependent variable was the "ABD index". Four predictors reached significance at 1 per cent level in the multivariate analysis, the alveolar bone loss 1970 ("ABL index 1970"), "Age", "Number of lost teeth" and "Russell's Periodontal Index" ("PI"). The coefficient of determination (R2) was 0.40. In a selected part of the material, consisting of individuals with at least 20 remaining teeth, the stepwise multiple regression analysis was repeated with the same 18 predictors. On this occasion two predictors reached significance at 1 per cent level, "PI" and "Smoking", and these two factors showed an interaction. PMID- 3088753 TI - [Clinical and microbiologic findings in periodontal therapy supplemented by antibiotics]. PMID- 3088754 TI - Characterization and fibrin-binding properties of different molecular forms of pro-urokinase from a monkey kidney cell culture. AB - Culture fluid of a monkey kidney cell culture was harvested every two days, for a two week period, in order to obtain urokinase in the zymogen form. Pro-urokinase was isolated by immunoadsorption chromatography and gel filtered on Sephadex G 150, which resulted in three peaks with pro-urokinase activity. SDS polyacrylamide gel electrophoresis showed that the first peak contained 55 kd pro urokinase, aggregated with high molecular weight contaminants, whereas the second and third peaks consisted of almost pure 55 kd and 30 kd pro-urokinase, respectively. The latter form represented a relatively unknown and inactive precursor of low molecular weight urokinase, which was, like 55 kd pro-urokinase, activatable with plasmin. In comparison with tissue-type plasminogen activator, 55 kd and 30 kd pro-urokinase only bound weakly to purified fibrin clots and fibrin-sepharose columns. The extent of binding of the two pro-urokinases and their plasmin-activated forms to fibrin-sepharose decreased in the following order: 55 kd pro-urokinase 30 kd pro-urokinase 55 kd urokinase 30 kd urokinase. These results indicate that the two precursors exhibited stronger binding to fibrin-sepharose than the corresponding active enzymes, and the two 55 kd forms exhibited stronger binding than the corresponding 30 kd forms. This indicates the importance of both the zymogen nature and an intact NH2-terminal part of the molecules for binding to fibrin. PMID- 3088755 TI - Study on the mechanism of action of heparin and related substances on the fibrinolytic system: relationship between plasminogen activators and heparin. AB - It is now generally well accepted that heparin and related substances increase the fibrinolytic activity in vivo. The stimulation of the amidolytic, plasminogenolytic and fibrinogenolytic activity of tissue plasminogen activator and urinary plasminogen activator through heparin was investigated in vitro. A concentration-dependent stimulation of the plasminogenolytic and fibrinogenolytic activity of both urinary and tissue-type plasminogen activators was observed in the presence of heparin. No heparin dependence was observed in the amidolytic assay. Heparin stimulates the plasminogenolytic activity of tissue plasminogen activators in the same manner as fibrin. Both activators form complexes with heparin; the heparin-binding-site seems to be identical or related with the fibrin-binding-site of tissue plasminogen activator. The physiological role of these interactions is discussed. PMID- 3088756 TI - Preparation of high purity factor VIII concentrates. AB - An improved process for producing high purity Factor VIII concentrate has been developed. The improvement was based on the combination of three precipitating agents (polyethylene glycol, glycine and sodium chloride) which heretofore have been used alone in a single step or in separate and distinct steps in a multi step process. The product was pasteurized in solution (60 degrees C, 10 hrs) to reduce possible risks of virus transmission. The purified product has significantly higher specific activity and lower fibrinogen and immunoglobulin levels when compared to other commercial concentrates. PMID- 3088758 TI - Solid-phase fibrin-tissue-plasminogen-activator activity assay (SOFIA-tPA): tPA but not UK is specifically detected. PMID- 3088757 TI - Synergistic actions of paf-acether and sodium arachidonate in human platelet aggregation. 2. Unexpected results after aspirin intake. AB - The effect of sodium arachidonate and paf-acether on the activation of human platelet rich plasma from volunteers 2.30 to 36 hours after 500 mg of aspirin intake was studied. Concentrations of paf-acether which induce a reversible aggregation in platelet rich plasma (PRP) (0.29-0.029 microM) and concentrations of sodium arachidonate (AA) which don't produce aggregation (0.75-1mM) on the PRP from these volunteers, induced full aggregation when added together. But no cooperation activity was achieved in the 2.30 hours sample. Contrarily to the in vitro studies performed in human normal PRP, ASA (200 micrograms/ml) or indomethacin(12 microM) added to the PRP were unable to suppress the cooperative aggregation effect; neither did apyrase (12U/ml), esculetin (10 microM) or nordihydroguaiaretic acid (0.1 microM) have any action on the activated platelets but the synergistic action is completely suppressed by BW 755C (0.1 mM). TXB2 formation is very low in all these activated samples and insufficient to cause platelet aggregation. These results suggest 2 behaviors of platelets: synergistic activity of paf-acether and exogenous AA in vitro on normal human PRP is mediated mainly through active metabolites of AA formed via cyclooxygenase, as was previously published. When cyclooxygenase is inhibited in vivo by administration of 500 mg ASA, the cooperative effect of agonists is still present but the active aggregating product(s) is probably, formed through a pathway different of that of the cyclooxygenase or lypoxygenase. PMID- 3088759 TI - Sex differences in mouse platelet aggregation. AB - The role of platelets in the sex difference observed in mouse thrombosis models was evaluated by examining platelet diminution in vivo after thrombotic challenge, and aggregation of mouse platelets in PRP. A fall in platelet count was observed in both sexes after i.v. injection of either arachidonic acid or the thromboxane agonist, U46619. Platelet diminution induced by high dose arachidonate (50 mg/kg) was significantly greater in males compared to female mice. Responses to U46619 were similar in both sexes. In PRP, male platelets exhibited a greater response than female platelets to both ADP (15 uM) and arachidonate (0.3 mM), but not to U46619 (4.6 and 6.9 uM). These results suggest that the gender difference in arachidonate-induced sudden death, in which males are more susceptible than females, is related to a sex difference in mouse platelet function. PMID- 3088760 TI - [Protein-calorie malnutrition. Diagnosis and preoperative parenteral nutrition of patients at risk]. PMID- 3088762 TI - [Diverticulosis of the vermiform appendix]. PMID- 3088761 TI - [Severe liver involvement during use of sodium valproate]. PMID- 3088763 TI - [Puncture of a peritonsillar abscess]. PMID- 3088764 TI - Managing costs in a defined benefit pension plan. PMID- 3088765 TI - Cost containment through asset management. PMID- 3088766 TI - Managing the cost of health care benefits. PMID- 3088767 TI - Labor unions and health care cost containment. PMID- 3088768 TI - Retiree medical plans--today's issues. PMID- 3088769 TI - Savings through claims audits. PMID- 3088770 TI - Pension plan termination: a sound financial move? PMID- 3088771 TI - Flexible compensation for effective benefit management. PMID- 3088773 TI - Xenobiotic metabolizing enzymes of rat liver nonparenchymal cells. AB - The nonparenchymal cells (NPC) of the liver are primarily located along the sinusoids and therefore are the first cells to encounter blood-borne xenobiotics. To study the possible role of the NPC in the metabolism of xenobiotics, populations of NPC and parenchymal cells (PC) were prepared from rats and various xenobiotic metabolizing enzyme activities investigated. The specific activity of every enzyme studied (ethoxyresorufin deethylase, benzphetamine demethylase, glutathione transferase, UDP glucuronosyltransferase, and microsomal epoxide hydrolase) was 12 to 1000% higher in the PC than in the NPC populations and the patterns of activities between the two populations were remarkably different. The NPC demonstrated a more dramatic induction of enzyme activities in Aroclor 1254 pretreated animals than did the PC. Moreover, despite the generally lower enzyme activities, even after induction, the NPC were damaged by biologically inert xenobiotics which can be metabolized to reactive intermediates. With some compounds, the concentrations required for producing similar damage was much higher in NPC compared with PC, while with other compounds, the NPC were affected by concentrations similar to those required for cytotoxicity in PC. Therefore, the NPC may contribute to the hepatic disposition of xenobiotics and may be adversely affected by reactive intermediates formed. Because of the distinctly different pattern of xenobiotic metabolizing enzymes in the two cell populations, the exact role of the NPC in the control of reactive metabolites and the toxicity produced by them will depend on the structural elements of the xenobiotic in question. PMID- 3088772 TI - Toxicity and evidence for metabolic alterations in 2,3,7,8-tetrachlorodibenzo-p dioxin-treated guinea pigs fed by total parenteral nutrition. AB - The effect of total parenteral nutrition (TPN) on the toxicity of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) in male, Hartley-strain guinea pigs was determined. At a single dose of 2 micrograms TCDD/kg, TPN-fed guinea pigs maintained body weight at a level which was slightly, but consistently, below that of the TPN-fed control animals. However, despite the sustenance of body weight, TCDD-treated animals died or were sacrificed due to morbidity between Days 8 and 24 following treatment. Approximately 50% of this group demonstrated a profound loss of body weight within a few days prior to death or sacrifice. With the exception of the pattern of weight loss, the signs of toxicity in the TPN fed, TCDD-treated animals were strikingly similar to those observed in TCDD treated guinea pigs fed ad libitum. Although livers from TCDD-treated, TPN-fed animals demonstrated increased content of lipid and cytochrome P-450, this tissue appeared to be morphologically and functionally comparable to that from TPN-fed controls. Of the blood chemistry examined, only the serum concentrations of 3,5,3'-triiodothyronine were significantly decreased in the treated animals fed by TPN. Results were also compared to TCDD-treated guinea pigs fed ad libitum and respective pair-fed controls. Many of the physiological and biochemical responses observed in animals fed ad libitum following TCDD treatment could be explained by a decrease in food consumption. This study demonstrated that although food consumption clearly accounts for the major effect of TCDD on body weight loss in guinea pigs fed ad libitum, additional physiological and/or biochemical alterations occurred which also contribute to body weight loss, other signs of toxicity, and subsequent lethality. PMID- 3088774 TI - Partitioning of renal zinc between metallothionein and ethylenediaminetetraacetic acid (EDTA) after treatment of rats with Ca(Na)2EDTA. AB - Calcium disodium edtate (EDTA) is a widely used chelator in the treatment of lead poisoning, although it also mobilizes other trace metals such as zinc. We have found that daily injection of 400 mg EDTA/kg body wt ip to rats results in an increase in the concentration of zinc (Zn) in the kidney when measured by atomic absorption spectroscopy. This increase is not associated with an induction of metallothionein (MT), a protein normally involved in the homeostasis of zinc. In fact, separation of kidney homogenate on a column of Sephadex G-75 demonstrates that virtually no Zn-MT remains in the kidney 24 hr after an EDTA injection, although after 3 days, Zn-MT levels appear to return to normal. Instead, increased renal Zn is found associated with residual EDTA. False high measurements of MT can be obtained from the Cd-saturation/hemoglobin assay due to the presence of residual EDTA in the kidney. Although nearly all of an injected dose of radiolabeled EDTA is rapidly excreted, 0.2 to 0.1% is retained in the kidney 1 day later; this is sufficient to account for the additional Zn. We propose that the small proportion of EDTA incorporated by pinocytosis into lysosomes in the renal cortical cells binds with all free Zn and subsequently depletes the MT concentration. Although the concentration of Zn measured in the kidney is elevated, there is actually less available for Zn-dependent activity. PMID- 3088775 TI - Influences of glutathione status on different cytocidal responses of monolayer rat hepatocytes exposed to aflatoxin B1 or acetaminophen. AB - In short-term primary monolayer cultures of rat hepatocytes, aflatoxin B1 (AFB1) causes a characteristic prelethal cytomorphological response in which peripheral attached cytoplasm contracts segmentally to form finger-like blebs. This response precedes lethal injury as detected by release of lactate dehydrogenase (LDH) into culture medium. We compared the influences of various modifiers of cellular glutathione (GSH) status on cytocidal responses of Fischer 344 rats hepatocytes exposed to AFB1 or acetaminophen (AAP), a hepatotoxin which does not produce segmental cytoplasmic contraction. N-Acetylcysteine (4 mM) reduced the degree of LDH release by AAP (4 to 16 mM) but was not protective against cell killing by AFB1, although it slightly reduced the percentage of hepatocytes with segmental cytoplasmic contraction at 6 hr. BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) at 40 microM markedly inhibited glutathione reductase and also strongly potentiated cell killing by AAP but did not significantly influence segmental cytoplasmic contraction or LDH release in response to AFB1. Diethylmaleate (40 to 160 microM), a depletor of hepatocellular GSH, and buthionine-D,L-sulfoximine (4 mM), an inhibitor of GSH synthesis, each did not alter hepatocyte killing by AFB1 but were strong potentiators of toxicity of AAP. AAP inhibited glutathione reductase but AFB1 did not. Total GSH concentrations at 6 and 18 hr were reduced by AAP and to a lesser extent by AFB1 in comparison with control cultures. These findings demonstrate that, in contrast to AAP toxicity, the characteristic mode of hepatocyte killing by AFB1 in monolayer cultures is substantially independent of induced alterations in GSH. These results indicate that GSH-dependent detoxification mechanisms do not play a major role in removing necrogenic metabolites of AFB1 in Fischer 344 rat hepatocytes. They further suggest that prelethal responses of AFB1-injured hepatocytes are not affected by GSH-dependent cytoprotective mechanisms. PMID- 3088776 TI - Nondetectable concentrations of human placental Ah receptors are associated with potent induction of microsomal benzo[a]pyrene hydroxylase in individuals exposed to polychlorinated biphenyls, quaterphenyls, and dibenzofurans. AB - Human exposure to polychlorinated biphenyls, quaterphenyls, and dibenzofurans occurred in an accidental food poisoning episode in Taiwan in 1979. Our objective was to evaluate the role of Ah receptors in the production of biochemical effects detected in placentas from exposed subjects. Placentas were obtained from pregnant women who were identified from a registry of exposed individuals. Benzo[a]pyrene (BaP) hydroxylase was quantified in placental microsomes and Ah receptor was investigated in placental cytosolic and nuclear fractions by a variety of receptor-binding techniques using 2,3,7,8-[1,6-3H]tetrachlorodibenzo-p dioxin ([3H]TCDD) as the ligand. Microsomal BaP hydroxylase was dramatically elevated in placentas of exposed subjects compared to those of nonexposed, nonsmoking control subjects. However, concentrations of displaceable [3H]TCDD binding in placental preparations from exposed or control subjects were uniformally low; approximately 1.0 fmol/mg cytosolic protein. Further evaluation of displaceable TCDD binding by sucrose-gradient sedimentation and hydroxylapatite column chromatography revealed that binding properties were different than those for the Ah receptor. These data suggest that extremely low concentrations of Ah receptors in human placenta may be sufficient to markedly elevate microsomal BaP hydroxylation. Alternatively, induction in human placenta may be mediated by a mechanism not requiring Ah receptor. PMID- 3088777 TI - Effect of dietary fat on aflatoxin B1-induced chromosomal aberrations in mice. AB - The effect on the frequency of aflatoxin B1 (AFB1)-induced chromosomal aberrations in bone marrow cells of mice fed diets containing increasing levels of sesame oil was investigated. Mice receiving either 9% or 12% sesame oil in their diet for 8 weeks presented a statistically increased AFB1-induced aberration rate as compared to those given a diet containing 3% sesame oil. These data suggest that the metabolism of a mutagen can be influenced by the dietary lipid intake of the test animal. PMID- 3088778 TI - Phenylethylmalonamide serum levels in patients treated with primidone and the effects of other antiepileptic drugs. AB - Data are presented for the serum levels of 2-ethyl-2-phenylmalonamide (PEMA) in patients receiving anticonvulsant medication. Statistical analysis of these data indicates that the serum level of PEMA, which is a metabolite of primidone, is affected not only by the dose of primidone but also by the serum levels of other prescribed anticonvulsant drugs. In particular, phenobarbitone is shown to be a major perturbation upon the PEMA serum level. PMID- 3088779 TI - Determination of free valproic acid levels by ultrafiltration. PMID- 3088780 TI - The C57B1/6 nu/nu, lpr/lpr mouse. III. Autoimmunity status. AB - C57B1/6 mice homozygous at the lpr (lymphoproliferation) locus display evident lymphadenopathy (in our B6 colony, primordially cervical lymph node enlargement) and autoimmunity (various autoantibodies). Four groups of mice corresponding to the diverse combinations of the lpr gene and the nu (nude, athymic) gene on the B6 genetic background have been compared for signs of lymphadenopathy. It occurred in all tested B6 +/+, lpr/lpr mice and none of the other groups (B6 nu/nu, +/+; B6 nu/nu, lpr/lpr and B6 +/+, +/+). B cell hyperactivity/autoimmunity was also evaluated by serum antibody analyses: higher serum immunoglobulin levels, anti-nuclear antibodies, anti-native DNA, anti-single stranded DNA, rheumatoid-like factors (anti-rabbit IgG), and natural antibodies against dinitrophenol and trinitrophenol haptens and their non cross reactive carriers: bovine serum albumin, hen egg albumin and keyhole limpet haemocyanin. Interestingly the levels of serum immunoglobulins and of some specific antibodies were somewhat higher in B6 nu/nu, lpr/lpr than in 'normal' B6 nu/nu, +/+, though they remained much lower than in B6 +/+, lpr/lpr animals. This suggests that the lpr gene may express its influence on the level of B cell activity in the absence of T lineage cells that would have normally matured in a thymus and that this effect of the lpr gene does not require the massive proliferation of T lineage cells observed in B6 +/+, lpr/lpr mice. PMID- 3088782 TI - The diagnosis of Schistosoma japonicum infection. Areas of uncertainty. PMID- 3088781 TI - Retrolental fibroplasia: update. PMID- 3088783 TI - Rapid repeated DNA replication during microgametogenesis and DNA synthesis in young zygotes of Plasmodium berghei. PMID- 3088784 TI - Schistosoma haematobium: effect of non-schistosomicidal drugs (tetracycline and sulphadimidine) on schoolchildren. AB - Pupils attending four secondary boarding schools in Mwanza Municipality, Tanzania, were examined parasitologically for Schistosoma haematobium. Prevalence of infection was highest in the age group 17 to 18 years in both sexes whereas the intensity was highest in the age group 15 to 16 years in girls and 17 to 18 in boys. Absence on grounds of sickness among the pupils studied was not related to the infection and the over-all academic performance was not clearly related to S. haematobium infection in either. Two drugs (tetracycline-HCL and sulphadimidine) commonly used for treatment of many bacterial infections in Tanzania were used. Administration of these drugs to schistosomiasis patients showed that both significantly lowered egg excretion and the degree depended on the dosage. Neither drugs affected the hatching of miracidia. It is speculated that the administration of both drugs might contribute to a higher accumulation of the eggs in the tissues. This effect could lead to more pathogenic effects as well as introducing an element of error in the studies on drug trials and chemotherapy. Treatment using metrifonate (Bilarcil) resulted in cure rates of 76% for girls and 93% for boys. PMID- 3088785 TI - Du confirmation. AB - The need for repeat antiglobulin testing to detect the Du phenotype in donor blood already labeled as Rh-negative was challenged. The confirmatory testing by hospital transfusion services rejected only 47 units in 2.6 million tested. The confirmatory antiglobulin test for Du currently required of hospital transfusion services could be omitted. PMID- 3088786 TI - The distribution of ABO and Rh(D) and selected high- and low-frequency antigens in the people in the Kingdom of Tonga. AB - The incidence of red cell A, B, and D antigens in 7903 people from the Kingdom of Tonga is reported. ABO and D typings were performed by the slide method while establishing a registry of potential blood donors. The results of selected high frequency antigens and one low-frequency antigen typing of 1009 donors also are reported. PMID- 3088787 TI - Induced tolerance to allogeneic pancreatic islet transplants. PMID- 3088788 TI - [Effect of HEBP on the remineralization of acid-etched enamel]. PMID- 3088789 TI - [Detection, in synaptic membranes of proteins, specific substrates for endogenous phosphorylation in the presence of GTP]. AB - Using the polyacrylamide gel electrophoresis (PAGE) of the synaptic membranes of proteins isolated from the rat brain cortex it is shown that on phosphorylation in the presence of [gamma-33P] GTP (5 and 10 microM) and 10-20-fold excess of unlabelled ATP the phosphorylation of protein with molecular weights of 41,000 and 49,000 Dalton greatly increased but the labelling of proteins with molecular weights of 54000 and 30,000 Dalton strongly decreased or was completely abolished. The addition of unlabelled ATP practically does not change the phosphorylation of the bands (proteins) with molecular weights of 86,000, 82,000, 46,000 Dalton and weakly decreased when labelling proteins with molecular weight of 59,000. The results obtained permit suggesting the existence of proteins- substrates of specific phosphorylation with GTP in synaptic membranes. PMID- 3088791 TI - Laser physics and tissue interaction. AB - An understanding of basic laser physics and tissue interaction is required to select and utilize the appropriate laser for a given indication. Biophysical principles demonstrate how in-vivo use differs from bench-top physics. Dosimetry studies help to point out the effects of lasers. PMID- 3088790 TI - [In vitro sensitivity testing of human kidney tumors to cytostatic drugs with a rapid in vitro test]. AB - We present a new modified in vitro culture assay for primary human renal cell carcinoma similar to the 'soft agar clonogenic assay'. However, the carrying out and expense of metrology are more simplified, allowing tumor-specific chemotherapeutic drug sensitivity testing under easier conditions. Twelve different samples of human renal carcinoma and one sample of a transitional cell carcinoma of the renal pelvis were tested for in vitro chemotherapy sensitivity using this modified colony-forming assay. The rate of tumor cells establishing in culture was 100%. Corresponding to clinical experience we observed a nearly complete resistance to the cytotoxic effects of standard chemotherapeutic agents at usual plasma concentrations in man. Only higher concentrated chemotherapeutic drugs showed in vitro therapeutic effects. The assay described here lasts about 7 days, which is beneficial from the clinical point of view. The modification of this in vitro chemotherapeutic drug treatment is unlimited for plasma concentration and duration of standard and experimental chemotherapeutic agents, drug combination and so on. So we have interesting scientific steps which could not have been undertaken under usual clinical-empirical conditions. PMID- 3088792 TI - Use of the CO2 laser in urology. AB - The CO2 laser emits coherent light in the far infrared region with an extremely short extinction length. Energy absorption at the impact site is very intense and results in a surgical incision characterized by a zone of vaporization surrounded by a narrow zone of thermal necrosis and sublethal thermal injury. Infected epithelium can be ablated precisely to a shallow depth so that the papillomavirus is killed and rapid healing can occur. The CO2 laser is the treatment of choice for condylomata acuminata that are extensive or recurrent, are within the urethral meatus, or occur during pregnancy, a period during which cytotoxic drugs are contraindicated. With this technique virtually all patients with condylomata acuminata can be cured rapidly with minimal morbidity, complications, or risk of recurrence. PMID- 3088793 TI - Endoscopic applications of laser energy. AB - Flexible fibers allow transmission of laser energy through endoscopes for treatment of urethral, bladder, and ureteral lesions. Nd:YAG laser destruction is probably the current treatment of choice for intraurethral condylomata acuminata, but results with urethral strictures are less encouraging. Although therapeutic advantages for laser treatment of superficial bladder tumors have not been established, the treatment appears to offer practical advantages over electrocautery resection. Laser treatment of invasive bladder cancer should not be considered an alternative to cystectomy, but may be useful in patients who are not candidates for radical surgery. PMID- 3088794 TI - Laser use in open surgery and external lesions. AB - The Nd:YAG laser, the CO2 laser, and the argon laser have all been used as cutting or hemostatic tools in open urologic surgery and in the treatment of skin lesions of the genitalia with the choice of instrument being dictated by the characteristics of each wavelength. Results to date in open surgical applications have not been dramatic. For the treatment of benign and malignant lesions of the external genitalia, lasers may prove to have a significant advantage over existing methods of treatment. PMID- 3088795 TI - [Intraoperative injuries of the abdominal cavity organs]. PMID- 3088796 TI - [Methods of sterilizing and preserving tendon transplants]. AB - The authors describe three methods for making tendon transplants by using chemical sterilizing and preserving means having no unfavorable effect on their biological and plasty properties. The methods are simple, reliable and fairly suitable for a wide supply of clinical institutions with tendon transplants. PMID- 3088797 TI - Economic and management considerations of a computer. AB - The extent to which a computer can be effectively employed in a veterinary practice depends to a large extent upon the size of the practice. Estimating defensible money investment in hardware and software prior to purchase is typically problematic because of the assumptions entailed in gauging potential return on capital. Successful software decisions flow principally from careful prepurchase planning and rigorous adherence to high standards of postpurchase support from the vendor selected. Staff involvement in the planning phase should be encouraged. The period of installation and implementation will probably be a stressful time in the practice. PMID- 3088798 TI - [The effect of the early feeding of solid and bulk foods on the dynamic development of the digestive processes in calves ina large-scale breeding facility]. AB - Digestive activities were studied in test calves (n = 12) in relation to age and feed intake. The calves were isolated after birth from adult cows. Since the 14th day of age, milk replacers were fed with concentrate feed mixture TG and alfalfa hay, i.e. the calves were in the period of plant feeding. The investigation lasted from the end of milk feeding (50th day) to the age of six months. Overall health condition was studied clinically. The characteristics of digestive activities studied in rumen fluid at weekly--monthly intervals were pH, ammonia content, total content of volatile fatty acids, content of particular volatile fatty acids, incidence and number of infusoria. At the age of 50 days, actual pH of rumen fluid was on the average 6.07 and it ranged from 5.84 to 6.76 in the next period. Ammonia content was the highest at the age of 50 days (21.49 mmol/l rumen fluid), then it dropped to 9.83 mmol/l rumen fluid at the age of 180 days. The average total concentration of volatile fatty acids (C2-C5) made 117.00 mmol/l during the first examination, it increased to 132.98 mmol/l at the age of 84 days, and it dropped to 94.16 mmol/l rumen fluid at the age of six months. A similar tendency was found in the volatile fatty acids. The infusoria were found out only at the age of 120 days--their numbers were 155 000 per ml; at the age of 180 days their numbers rose to 368 000 per ml rumen fluid. No disorders of health condition were recorded during the experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3088799 TI - [Growth in weaned piglets and levels of iodothyronines in the blood during the administration of thyroactive substances]. AB - In five trials with 100 piglets we studied the effects of thyreoglobulin, potassium nitrite and the thyreostatic preparation Carbimazol, which were added to a complete starter in the period from early weaning to the age of four weeks. Changes in the concentrations of thyroxine (T4) and triiodothyronine (T3) in the blood serum of control unmedicated piglets weaned from the sows can be characterized, after a short rise, by a decrease which stopped usually in the fourth week, accompanied by higher body weight gains. The lowest drop of T4 level was recorded in the group given potassium nitrite, with 21% methemoglobin, having the highest actual and relative weight gains. The T4 and T3 levels were not influenced by thyreoglobulin. They were decreased by Carbimazol by more than two thirds of the values which were usual at weaning if Carbimazol was administered at the highest rate of 60 mg per 1 kg of feed; neither was the growth of body weight nor feed consumption per unit of weight gain negatively influenced. An application of thyreotropic hormone on the 14th day after weaning demonstrated an inhibition of iodothyronine secretion in piglets which had been given Carbimazol, and a good response in control piglets. We drew a conclusion that the decrease in T4 and T3 levels after early weaning did not occur when iodothyronine intake with mother milk was interrupted nor was it caused by iodine deficiency, nor was it a primary cause of the reduced growth rate of piglets. PMID- 3088800 TI - [The development and growth of subcutaneous adipose tissue in various production types of domestic fowl]. AB - Hyperplasia and hypertrophy of fat cells of the subcutaneous adipose tissue were studied in different production types of fowl in the post-incubation period. The cocks and hens of laying type were found to have fewer and smaller fat cells than the birds of broiler type. The highest hyperplasia was recorded in the first nine weeks of age, then followed a decrease, lasting until the 25th week. Hypertrophy continued step by step throughout the period of study and increased when hyperplasia decreased. The differences between sexes increase during sexual maturation: in the hens the hypertrophy of cells increases and hyperplasia does not decrease so quickly as in the cocks. Before sexual maturity, hypertrophy as well as hyperplasia are somewhat higher in the cocks. PMID- 3088801 TI - [Relation between the incidence of antibodies against Leptospira interrogans in working dogs and in free-living small mammals]. AB - Three localities were chosen in the borderland of the South Bohemian Region to investigate the problems and relations (if there are any) between the incidence of antibodies to Leptospira interrogans (L. i.) in wild ground small mammals and dogs moving in the same environment. In these regions, service dogs work as border guards every day. Blood samples of dogs at these localities were taken at about three-month intervals (from the June 1982 to the October 1984) to investigate the antibodies to L. i. serovars. Parallelly, wild ground small mammals and wild birds were caught at the same localities to be subject to the same examinations. A close relationship between the incidence of L. i. antibodies in ground small mammals and in service dogs was demonstrated at all three localities. At localities no. 1 and 2, the serovar grippotyphosa was found to be dominant in service dogs, which was also found in small rodents. On the other hand, the serovar icterohaemorrhagiae dominated in service dogs at locality no. 3. When changes in the incidence of L. i. antibodies were studied in service dogs and in wild small mammals, the peak of incidence at localities 1 and 2 was in the other half of the year; this relates to the usual maximum incidence in the natural reservoir of the serovar grippotyphosa, i.e. in rodents. On the contrary, at the third locality the peak of incidence of L. i. antibodies was recorded in the winter 1983-1984.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3088802 TI - [Clinical use of yohimbine as an antagonist of xylazine depression of the central nervous system in cats]. AB - Antagonizing effects of various doses of yohimbine on a xylazine depression of the cerebroneural system (CNS) were studied in cats. Administration of various doses of yohimbine was investigated with respect to its antagonizing effects on various doses of xylazine. The time of CNS depression induced by commonly recommended doses of xylazine (2-4 mg/kg live weight) was shortened statistically significantly by intramuscular injections of yohimbine at a dose of 3 mg per kg live weight. After this yohimbine dose, the animals recovered consciousness already 10-15 minutes from application, with the complete resumption of reflexes. Preventive administration of the same dose of yohimbine hindered reliably the full development of CNS depression after the two xylazine doses (2 and 4 mg/kg live weight). PMID- 3088803 TI - [Use of the hemolytic interaction phenomenon in the typing of Campylobacter sp]. AB - Various identification schemes are used for the typification of the strains of Campylobacter sp.; some of them are based on the evaluation of tolerance to salt, ranging from 0 to 3.5%, others on the evaluation of the temperature ranges (0-45 degrees C), etc. During the study of collection strains as well as newly isolated strains the "producing - not producing" tests were found to be better than the "sensitive-resistant" tests. The evaluation of the tolerance of each strain is too much dependent on the given batch of nutrient medium. Microtests are undoubtedly reliable but depend on the age of the microorganism culture. High importance is attached to the demonstration of Natrium hippuratum hydrolysis, the fast method being more advantageous. In this paper a proposal of applied micro test is presented, together with a proposal for the use of the phenomenon of haemolytic interaction (PHI). PMID- 3088804 TI - [Magnesium in the blood and urine of cows during various stages of the reproductive interval being fed summer and winter feed rations]. AB - Magnesium concentration was investigated in the blood plasma and urine of 3460 cows in the course of four green-feeding seasons and four winter feeding seasons in 1980 to 1984. A decrease in the magnesium content in blood plasma was found to intensify in the last six weeks of gravidity. In the first stage of lactation the magnesium concentrations of plasma begin to grow to reach a relative maximum in the cows in the second stage of lactation. These regularities apply to both the summer and winter feeding seasons. The magnesium content in urine has a similar pattern. The summer values of the magnesiemia of whole cow populations are significantly higher than the winter values. Tendencies to lower magnesium concentrations generally prevail in both blood plasma and urine; these tendencies are most conspicuous in the cows in the last six weeks to parturition. As a rule, the concentrations of magnesium in urine were lower in summer than in the season of winter feed rations. As for the contents of the blood plasma magnesium of the cow populations as well as individual cows, there are considerable differences between various stages but the trends are the same in all groups. In the green feeding season the range of fluctuation of the magnesiemia values is larger than in the winter feeding season. The same tendency of changes in individual groups was also recorded in the magnesium concentrations in the urine of cows in different stages. However, the direction of the changes did not always correspond to the direction of the changes in the blood plasma. A practical requirement has been derived from the results of the study that magnesium contents should be increased in the feed rations given to high-pregnant cows and cows in the first lactation. PMID- 3088805 TI - [Relation between the concentration of sodium and potassium in the erythrocytes of dairy cows and the concentration of these elements in the plasma and urine and the level of blood glucose]. AB - Blood and urine samples of 180 dairy cows from 12 herds were examined. Sodium and potassium concentrations were determined in erythrocytes, whole blood, plasma, urine, and glucose concentration in blood: the interrelations were compared. Sodium and potassium concentrations in erythrocytes were 85.15 +/- 11.45 mmol/l, and 25.93 +/- 7.81 mmol/l, respectively. A statistically significant relation was found between sodium and potassium concentrations in erythrocytes (r = 0.3467+++) and the content of electrolyte in blood cells and in whole blood (Na: r = 0.5336+++; K: r = 0.3561+++). No statistically significant relation of intraerythrocyte concentration of both electrolytes was confirmed with respect to the other characteristics (sodium and potassium concentrations in plasma and urine, and glucose concentration in blood). In the conditions of routine laboratory diagnostics in clinically healthy cows, determinations of intraerythrocyte sodium and potassium do not broaden possibilities of evaluating the metabolic state of these electrolytes and cannot be used as the characteristics of energy insufficiency. The cannot replace the analyses performed in serum and urine. PMID- 3088806 TI - [Fluctuation in the concentration of sex steroids and aflatoxin B1 in the seminal plasma of boars and its relation to sperm production]. AB - The concentration of testosterone, 17-beta oestradiol and aflatoxin B1 were studied in the semen plasma of 21 boars of four breeds for the period of twelve months. The following spermiological parameters were investigated: semen volume, sperm concentration, percentage of abnormal spermatozoa, and survival of spermatozoa. The fertilizing capacity of ejaculates was evaluated according to the conception rate of sows and gilts after the first insemination, according to the average number of piglets per litter and average number of live-born piglets per litter. The highest aflatoxin B1 residues in sperm were recorded in March to May and were related with aflatoxin concentration in feed ration. The group of boars with fertility disorders had more aflatoxin in their sperm (up to 100 pmol . l-1), lower sperm concentration, lower survival of spermatozoa, and a larger proportion of abnormal spermatozoa. The year season had a significant influence on the concentration of the hormones. The highest average value of testosterone (10.2 +/- 1.28 nmol) was obtained in autumn and lower values were recorded in winter. The changes in 17-beta estradiol concentration were similar to the changes in testosterone content, with the maximum value in November (0.249 nmol X 1(-1]. The boars with reproduction disorders had a significantly lower concentration of 17-beta oestradiol. Significant correlations were found between the concentration of the hormones, semen volume, and sperm concentration. 17-beta oestradiol also had a significant positive correlation to abnormal spermatozoa and to the activity of aspartate aminotransferase. PMID- 3088807 TI - [Dynamics of basic hematologic values in ewes during the course of a year]. AB - Basal hematological values were studied in ten primiparous ewes of Merino breed at 15 time intervals in the period from birth to the last decade of the next gravidity. The mean erythrocyte counts ranged from 6.5 to 10.3 T . l-1, hemoglobin content from 101.3 to 121.3 g per l, hematocrit value from 0.32 to 0.37 1 per l, mean corpuscular hemoglobin concentration from 29.97 to 34.22 g per dl, mean corpuscular hemoglobin from 11.17 to 16.61 pg, corpuscular volume from 35.03 to 55.37 fl. The mean leucocyte counts were from 4.98 to 9.93 G . l-1, with 25.8 to 60.5% neutrophil granulocytes with segmented nuclei, 0.1 to 2.6% neutrophil granulocytes with rodlike nuclei, 0.8 to 8.7% eosinophil granulocytes, 0.0 to 0.33% basophil granulocytes, 30.3 to 71.2% lymphocytes and 0.4 to 4.5% monocytes. The quality of red blood component was not negatively influenced by a high degree of gravidity. In the time of parturition, neutrophil granulocytes highly dominated over the other types of white blood cells; the counts normalized since the seventh day post partum. Although statistically significant differences were calculated for some time intervals, the values were within the physiological limits. PMID- 3088808 TI - [The growth of abdominal adipose tissue in various production-type of domestic fowl]. AB - At hatching, the abdominal fatty tissue is less developed than the subcutaneous fatty tissue. However, it grows more intensively during the post-incubation period through both the hyperplasia and hypertrophy of the fat cells. In the cocks, hyperplasia reaches its peak at the age of 9 weeks, followed by a decrease; then hyperplasia continues until the age of 25 weeks. In the hens the peak of hyperplasia comes later, at the age of 14 weeks; then it decreases until the age of 25 weeks is reached. Hyperplasia and hypertrophy are more pronounced in the early period and are somewhat higher in the cocks. During the period of sexual maturation both processes are more intensive in the hens; owing to them, the total weight of the abdominal fatty tissue of hens increases both absolutely and relatively in comparison with the cocks. The cellularity of the first population of adipocytes is assumed to culminate at the age of three to five weeks. Then follows the cellularity of the second population which persists throughout sexual maturation. The pictures of hyperplasia and hypertrophy are qualitatively the same in different production types of fowl, but the size is twice as large in the broiler type than in the laying type of fowl. PMID- 3088810 TI - Pathogenesis of placentitis in the goat inoculated with Brucella abortus. II. Ultrastructural studies. AB - Pregnant goats were inoculated intravenously or in uterine arteries with Brucella abortus, and tissues from the uterus and placenta were examined by electron microscopy. Identification of B. abortus in placentae was with antibody-coated colloidal gold. B. abortus was first seen in phagosomes of erythrophagocytic trophoblasts and in the rough endoplasmic reticulum of chorioallantoic trophoblasts. Subsequently, trophoblast necrosis and ulceration of chorioallantoic membranes were present. Coincidently, B. abortus was present in the lumen of placental capillaries. In late stages of infection, placental vasculitis was present, and placentomal trophoblasts were separated from maternal syncytial epithelium. In lesions with vasculitis, large numbers of B. abortus were in connective tissue of chorionic villi. Within the placentome, trophoblasts that lined chorionic villi contained no intracellular bacteria and were separated from B. abortus by intact basement membranes. These results suggest that bacteremic B. abortus is endocytosed by erythrophagocytic trophoblasts and that B. abortus replicates in the rough endoplasmic reticulum of chorioallantoic trophoblasts. Replication of brucellae in trophoblastic rough endoplasmic reticulum is unique; we believe that B. abortus may utilize endoplasmic reticulum for synthesis and glycosylation of bacterial membrane proteins or that B. abortus catabolizes trophoblast secretory proteins. PMID- 3088809 TI - Pathogenesis of placentitis in the goat inoculated with Brucella abortus. I. Gross and histologic lesions. AB - Pregnant goats were given Brucella abortus intravenously or in uterine arteries, and tissues from the uterus and placentae were examined at various post inoculation intervals to study mechanisms of placental infection. Placentitis was present by 5 days post-inoculation and abortions occurred within 11 days. B. abortus was identified in placentae by light microscopy and immunoperoxidase techniques. B. abortus was first seen in erythrophagocytic trophoblasts of the placentome. Subsequently, high numbers of B. abortus were seen in periplacentomal chorioallantoic trophoblasts. Trophoblast necrosis, chorioallantoic ulceration, and large numbers of B. abortus in chorionic villi were present in later stages of infection. These results suggest that entry and replication of B. abortus in trophoblasts precede placentome and fetal infection and that trophoblasts are the source of B. abortus for these tissues. Experimental caprine brucellosis closely resembles bovine and ovine brucellosis and it provides a model to study the intracellular development of B. abortus in trophoblasts. PMID- 3088811 TI - Ocular angiosarcoma in the horse: morphological and immunohistochemical studies. AB - Angiosarcomas arising in ocular tissues of four aging horses are described. Tumors were locally invasive and eventually metastasized via the mandibular and cervical lymph nodes. Pathologically, the tumors contained well-differentiated regions, in which vascular channels were lined by pleomorphic endothelial cells, as well as poorly-differentiated regions, in which vascular channels were either rudimentary or absent. Red blood cells were scare in vascular structures formed by the tumors. Factor VIII related antigen (VIII:RAg), a blood vascular endothelial marker, was demonstrated by immunohistochemistry in tumor cells in both the well-differentiated and poorly-differentiated regions. The results suggest that ocular tumors arose in blood vascular endothelium and represented true hemangiosarcomas although a lymphatic endothelial origin could not be excluded. Immunohistochemical demonstration of VIII:RAg is a valuable adjunct to conventional stains in the diagnosis of equine vascular neoplasia. PMID- 3088812 TI - The morphology and behavior of feline cutaneous mastocytomas. AB - Correlation of histopathology with the behavior of cutaneous mastocytomas in 85 cats revealed two distinct histologic subtypes which were predictive of biologic behavior. The first subtype comprised 65 cats of various breeds which had solitary, discrete, dermal tumors composed of slightly atypical mast cells. Most tumors in this group were histologically and behaviorally benign. However, seven solitary tumors with marked anisocytosis and mitotic activity recurred or spread to other sites within 2 to 3 months. The second subtype occurred in 18 cats which had discrete subcutaneous nodules composed primarily of histiocyte-like cells with equivocal cytoplasmic granularity after staining with toluidine blue. They were identified as mast cells by electron microscopy. Seventeen of the 18 affected cats were Siamese. The histiocytic mastocytomas occurred predominantly in young cats (less than 4 years) and were usually multiple. In the four cats of this group for which we have prolonged follow-up data, the tumors underwent apparently spontaneous regression within 2 years of initial tumor detection. Two other cats had tumors which contained mixtures of mast cell and histiocytic morphologies. PMID- 3088813 TI - Morphologic lesions in Brucella abortus infected ovine fetuses. PMID- 3088815 TI - Veterinary education. PMID- 3088814 TI - Antibodies reactive with Taylorella equigenitalis in equine sera. PMID- 3088816 TI - Humoral antibody response to glutaraldehyde-treated antigens of Dermatophilus congolensis. AB - Glutaraldehyde-treated whole cell antigens (GA.WcA) of Dermatophilus congolensis induced in guinea pigs immunological memory in contrast to cell wall antigens treated similarly (GA.CwA). However, GA.WcA could not induce a secondary response in animals primed with untreated WcA while GA.CwA on the other hand did stimulate a secondary response in animals primed with untreated CwA. Primary antibody production was induced by both GA.CwA and untreated CwA to a similar level in their respective hosts but it was the secondary response that was found similar in response to GA.WcA and untreated WcA. However, both untreated WcA and CwA induced primary and secondary antibody production in their respective hosts though these responses were considerably higher in guinea pigs given untreated CwA. This study showed that both untreated and GA-treated antigens of D. congolensis are capable of stimulating antibody production in guinea pigs but they differ in their levels of stimulation. PMID- 3088817 TI - Antigenic diversity of Theileria annulata macroschizonts. AB - A series of monoclonal antibodies has been produced which reacts with the intracellular macroschizont of Theileria annulata, and this series has been used to examine the level of antigenic diversity between and within stocks of the parasite in addition to species specificity within the genus. The majority of the monoclonal antibodies (six of eight) reacted with all stocks tested and four were species-specific. Two monoclonal antibodies detected variation between stocks and within stocks. The variation within a stock was manifest as only a proportion of the macroschizonts reacting with the monoclonal antibody. This was demonstrated as being due to the strain containing more than one antigenic type of parasite by cloning the infected lymphocyte cell line and showing that the resulting cloned cell lines were antigenically homogeneous. The variation between stocks allowed them to be divided into three groups on the basis of antigenic profile. PMID- 3088818 TI - Effects of different doses of dog-derived Sarcocystis sporocysts on growth rate and haematocrit in lambs. AB - Four-week-old lambs at pasture were dosed with dog-derived Sarcocystis sporocysts. No difference in growth rates was apparent at a dose of 1 X 10(3) sporocysts per lamb. The minimum dose required to depress growth rate was 2.5 X 10(3) sporocysts per lamb: at 4 weeks post-inoculation (w.p.i.) the weight gain of lambs infected with this dose was 0.6 kg less than the non-infected controls (P less than 0.05). At 11 w.p.i. the difference was 0.7 kg, but this was not significant because of the greater average body weights of both groups. Lambs given 5 X 10(3) sporocysts showed significant depression of weight gain at both 4 and 11 w.p.i. Haematocrit levels at 4-5 weeks post-inoculation were depressed by doses as low as 1 X 10(3) sporocysts. PMID- 3088819 TI - Experimental Sarcocystis levinei infection in buffalo calves. AB - Six buffalo calves were orally inoculated with 3 graded doses of sporocysts of Sarcocystis levinei (0.5, 1.0 and 2.0 million sporocysts; 2 calves for each dose) while two more calves were kept as uninoculated controls. One calf from each group was killed at 30 days post infection (DPI) and the other at 80 DPI. Inoculated calves showed a dose dependent response. The calves inoculated with 0.5 and 1.0 million sporocysts did not manifest any clinical signs of disease up to 80 DPI. One of the two calves inoculated with 2.0 million sporocysts showed clinical signs of weakness, emaciation and anaemia during the 5th week post infection. The other calf remained healthy until it was killed at 30 DPI. Pale liver tissue, gelatinization of fat and haemorrhages in the heart were observed in one calf inoculated with 2.0 million sporocysts; only microscopic lesions were seen in other calves. Schizonts and merozoites were not observed in any calf. Mature sarcocysts were observed in cardiac and skeletal muscle of calves killed at 80 DPI whereas no sarcocysts were seen in calves killed at 30 DPI. PMID- 3088820 TI - Hazards to health from environmental lead exposure: a review of recent literature. AB - There are adequate demonstrations of the adult and pediatric health risks associated with lead exposure. This document presents the scientific facts surrounding human health effects as well as providing an interpretation of some of the animal toxicology studies. There are numerous circumstances where economic and societal pressures have resulted in the continued use of materials that are potentially toxic, hazardous and injurious to the public health and welfare. While declining, the present use of lead in gasoline and its airborne release from smelting and metal refining industries located near metropolitan centers is no exception. The demonstration that continued lead exposure from airborne sources results in intellectual deficiency should be sufficient to result in the mobilization of public health resources and the minimization or elimination, if necessary, of such hazards to the public welfare. Based on this review, this is the position that is suggested by the authors of this document. PMID- 3088821 TI - Production of Brucella abortus-specific protein A-reactive antibodies (IgG2) in infected and vaccinated cattle. AB - The IgG2 anti-Brucella antibody response of cattle to Brucella vaccination and infection was measured. Three groups of animals were studied; Group 1 contained 11 non-vaccinated cows, Group 2, 17 cows vaccinated with a low dose of Strain 19 vaccine and Group 3, 17 cows vaccinated with a high dose of Strain 19 vaccine. All animals were challenged at Week 33 with an infectious isolate of B. abortus (Strain 2308). Studies of the IgG2 antibodies response indicated an absolute correlation between anti-Brucella IgG2 levels and infection of the animal. All animals showing reciprocal titers of greater than or equal to 3000 (16 of 45 tested) were found to be positive for the challenge organism at slaughter. Animals with reciprocal IgG2 titers less than or equal to 1000 (29 of 45 tested) were found to be negative for the challenge organism at the time of slaughter. The predictive value of IgG2 antibody levels for infection held for animals in all three groups and consequently this suggests that monitoring of specific IgG2 anti-Brucella antibody levels may be of value in detection of Brucella-infected cattle. PMID- 3088822 TI - Comparison of an enzyme-linked immunosorbent assay using monoclonal antibodies and a complement fixation test for cattle vaccinated and infected with Brucella abortus. AB - A competitive enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody conjugated to horseradish peroxidase MA(A) and a complement fixation test (CFT) were applied to sera collected over a two-year period from 60 cattle challenged with Brucella abortus strain 544. Forty-eight of the cattle were previously vaccinated with B. abortus strain 19 (S19) or B. abortus strain 45/20 (45/20). After challenge 33 of the cattle remained uninfected and nine of the 27 infected cattle showed aberrant reactions by the CFT. The performance of the MA(A) ELISA was as follows: after vaccination, the MA(A) ELISA, like the CFT, was unable to differentiate infected cattle from those recently vaccinated with S19. After challenge the MA(A) ELISA gave results comparable with the CFT for those cattle with aberrant reactions. For the non-infected cattle there was a similar number of weeks after challenge when both tests were negative. It is suggested that the main advantage of the MA(A) ELISA when compared with the CFT lies in its relatively simple test procedure. PMID- 3088823 TI - Effect of EDTA-tris on an Escherichia coli isolate containing R plasmids. AB - Solutions of ethylenediaminetetraacetate (EDTA)-tris combined with antibiotics have been shown to be effective in treating selected cases of persistent bacterial infections. Basic techniques in microbial genetics, including mating frequencies, chemical elimination of R plasmids, isolation of plasmid DNA and agarose gel electrophoresis, were used to determine if EDTA-tris has a curing effect on an R plasmid as part of its clinical action. Results of this study indicated that EDTA-tris by itself eliminated an antibiotic resistance marker from a clinical isolate of Escherichia coli and when combined with another chemical curing agent altered the isolate's mating frequency. PMID- 3088824 TI - [Demonstration of ligands for antibodies against the M protein on the virion surface of the Newcastle disease virus (NDV)]. AB - Demonstrated was the presence of ligands for antibodies to the M-protein on the surface of NDV virions, using the hemagglutination-inhibition reaction, the immunodiffusion test in agar gel, the indirect variant of the enzyme-linked immunosorbent assay, and the immunosorbent micromethod with nitrocellulose membranes. Data spoke of transmembrane interactions between the M-protein and the glycoproteins of the envelope, which was of basic importance with regard to the biologic role played by this essential structural virus protein. The presence of ligands made it reasonable to believe that the M-protein played a part in the building up of antiviral immunity. PMID- 3088825 TI - [Age and sex characteristics of the level of thyroid hormone synthesis in the Camborough hybrid]. AB - Investigations were carried out with 320 pigs of the Camborough hybrid, differentiated by sex at the age of one, two, three, and four months. The dynamic was followed up of T-3, T-4, and FT-4 in dependence on the age and sex. Some quantitative discrepancies were established in the level of these indices for both males and females and the ages under study. The physiologic parameters of thyroid hormone synthesis were determined along with the age- and sex-associated differential ranges of T-3, T-4, and FT-4. PMID- 3088826 TI - [Superovulation and the production of embryos in the water buffalo (Bubalus bubalis) in Bulgaria]. AB - A total of thirty water buffalo cows aged 3 to 8 years were treated for superovulation over the July-October period. Nine of the animals were injected with FSH at the rate of 40 mg at 12-hour intervals in the course of 4 consecutive days, and the remaining 21 animals were injected with 3,000 IU gestyl in the middle of the luteal phase. Forty-eight hours after stimulation started both groups were treated with 500 micrograms cloprostenol. Five out of the 9 buffalo cows (55.5 per cent) of group I and 15 out of 12 buffalo cows (71.4 per cent) of group II manifested estrus at an average interval of 44.4 +/- 3.6 and 40.5 +/- 3.29 hours, respectively, following the application of cloprostenol. The superovulatory treatment of the animals of the two groups led to average values of 5.6 +/- 1.89 and 4.0 +/- 0.98 corpora lutea and 1.0 +/- 0.63 and 2.7 +/- 1.41 follicules larger than 8 mm; 2.6 +/- 1.60 and 2.1 +/- 0.94 embryos of high quality were obtained through the use of a nonsurgical method of flushing. PMID- 3088828 TI - Expression of the antigen detected by the monoclonal antibody Ca 19.9 in human breast tissues. AB - The incidence and significance of the expression of the antigen defined by the monoclonal antibody Ca 19.9 (Sialyl Lea) has been assessed in human breast tissue. Frozen and formalin-fixed, paraffin embedded specimens of normal, hyperplastic, pregnant breast and carcinomas were examined using an immunoperoxidase technique. Ductal and acinar epithelium of normal and hyperplastic tissues showed variable reactivity in frozen sections but there was a reduction in staining in comparable samples after fixation and processing, such that in many instances only focal ductal epithelium reacted. A distinctive feature in the pregnant breast was the absence of staining in acini showing differentiated secretory activity, despite a reaction in adjacent nonsecretory acini and ducts. The overall incidence of detection of the Ca 19.9 antigen in breast carcinomas was 62%, but in half of these only a small number of cells stained. A significant relationship between expression of Sialyl Lea and poor differentiation of carcinomas was identified, but there was no correlation with local lymph node status. In contrast to the non-malignant tissue fixation and processing had little effect on the reactivity of carcinomas. It is suggested that this difference may be quantitative in nature, with malignant breast showing much greater expression, or be related to organisation of the antigen. The observations concerning carcinomas and pregnant breast indicate that the synthesis of the Ca 19.9 antigen is related to the state of differentiation and functional activity of human breast. PMID- 3088827 TI - Ultrastructural characterization of fundic endocrine cell hyperplasia associated with atrophic gastritis and hypergastrinaemia. AB - Clinical and experimental evidence indicates that carcinoid tumours of the stomach fundic mucosa represent another example of hormone-dependent neoplasm, gastrin being the hormone involved in tumour induction. In this context hyperplasia of fundic endocrine cells associated with chronic atrophic gastritis (CAG) and hypergastrinaemia is regarded as the most frequent preneoplastic lesion. However, the cell type involved in this hyperplasia has not been clarified. To elucidate this problem fundic endocrine cells were characterized ultrastructurally in 9 patients from which endoscopic gastric biopsies were obtained. ECL cells were the most frequent cell type in 8 cases, in 4 of which they were more numerous than all other cell types taken together. D1 cells were the most frequent type in one case while they were inconspicuous in the other cases. P cells were found with a frequency in each case intermediate between that of ECL cells and that of D1 cells. These results indicate that fundic endocrine cell hyperplasia occurring in hypergastrinaemic CAG is in most cases cytologically similar to that found in other hypergastrinemic conditions, in which the gastrin-dependent ECL cells were already found to prevail. They also explain why fundic carcinoids arising in CAG are mostly composed of ECL cells. The relation between ECL, D1 and P cells, if any, remains obscure. PMID- 3088829 TI - The sinusoidal barrier in alcoholic patients without liver fibrosis. A morphometric study. AB - Alcohol induces morphological changes in the endothelial and perisinusoidal cells at the fibrotic stage of alcoholic liver diseases. Directly or indirectly, through hemodynamic disturbances linked to the enlargement of steatotic hepatocytes, alcohol may modify this barrier before the onset of fibrosis. Liver biopsies were obtained from control and from alcoholic patients and perfusion fixed. Volume and surface densities of endothelial cells, perisinusoidal cells and their processes were measured. Liver histology was normal in the 2 groups except for steatosis in the alcoholics. Volume densities represented 8.2%, 4.7% and 3.2% of the sinusoid in controls for endothelial cells, perisinusoidal cells and their processes whereas surface densities represented respectively 0.5, 0.23, 0.21 m2/cm3 of sinusoid. Morphometric values were not significantly different in the alcoholic patients. In none of the alcoholic patients did fine morphological studies of sinusoidal cells give any indication of the possible evolution of the alcoholic disease towards fibrosis. These results indicate that in the group of patients studied, alcohol, before the fibrotic stage, did not significantly alter the sinusoidal barrier. PMID- 3088831 TI - [Problems in determining energy supply in patients requiring artificial nutrition]. PMID- 3088830 TI - Nucleotide sequence of the 26 S mRNA of the virulent Trinidad donkey strain of Venezuelan equine encephalitis virus and deduced sequence of the encoded structural proteins. AB - A cDNA clone containing all of the 26 S mRNA coding region of the RNA genome of Venezuelan equine encephalitis (VEE) virus, virulent strain Trinidad donkey (TRD), has been constructed and sequenced. The nucleotide and deduced amino acid sequences of the 26 S RNA of VEE virus conform to the general organization of the alphavirus subgenomic mRNA. Excluding the poly(A) tail, the VEE 26 S RNA is 3913 nucleotides long with a protein coding region of 3762 nucleotides. Codon usage in the translated region is nonrandom and correlates well with that reported for Sindbis (SIN), Semliki Forest (SF), and Ross River (RR) alphaviruses. Highly conserved sequences of 19 to 22 nucleotides representing putative replicase recognition sites occur at the 26 S RNA junction region of the 42 S genomic RNA and at the 3' terminus immediately preceding the poly(A) tail. The conserved sequence at the 26 S/42 S junction region of VEE virus differs from that of other alphaviruses in that an ochre termination codon (UAA) is substituted for a GGU (Gly) codon present in the other viruses. The 5' and 3' noncoding regions (30 and 121 nucleotides, respectively) of the VEE 26 S RNA are shorter than has been reported for several other alphaviruses. The approximate transmembrane domains of the VEE E1 and E2 envelope glycoproteins have been identified. VEE E1 contains a single asparagine-linked glycosylation site, whereas E2 has three such sites, all of which are apparently glycosylated. The deduced amino acid sequence of the VEE polyprotein shows an overall homology of 44 to 46% with the precursor polyproteins of SIN, SF, and RR viruses. VEE virus capsid, E1, and E2 structural proteins show 43 to 46%, 50 to 53%, and 36 to 41% homology, respectively, with the cognate proteins of SIN, SF, and RR viruses. PMID- 3088832 TI - [The TRH test in the mothers of children with cleft defects of the face and in women with infertility]. PMID- 3088833 TI - [Comparative immunochemical studies of soluble leukocyte antigens in atherosclerosis of the coronary vessels]. PMID- 3088834 TI - [Sensitivity of the pituitary-ovarian system of animals to the nonhormonal preparation RL-S]. AB - A hypophysis-ovarian system of barren cows was shown to be highly sensitive to the effect of the preparation RL-S. The preparation possessing a simple chemical structure, proved to regulate the functional activity of endocrine glands. After treatment with the preparation RL-S concentration of estradiol was increased 1.81 fold in blood plasma of cows studied as compared with controls, while content of luteinizing hormone was elevated by 12.3%. In the groups of experimental animals the sexual cycle was normalized as content of progesterone was increased in blood with simultaneous decrease in estradiol concentration. PMID- 3088835 TI - [Changes in the amine oxidase activity of human serum during different types of anesthesia and hyperbaric oxygenation]. AB - Some types of anesthesia, used usually in labor anesthesia (sodium hydroxybutyrate, lexir) or in abdominal delivery (neuroleptanesthesia, cetalar narcosis, electroanesthesia) did not affect distinctly the activity of amine oxidases in blood sera of women in labor and of fetus. In some groups of women in labor the neonates were found, blood serum of which exhibited high activity of diamine oxidase, not observed in normal state. A slight decrease in deamination of benzylamine (20%) and 4-nitrobenzylamine (30%) was observed in patients with gynecological diseases within 2 and 3 days after operations. If intestinal paresis developed in the patients within the postoperational period deamination of these substrates was decreased by 75-80% in blood sera. After 2-4 courses of hyperbaric oxygenation a slight but statistically distinct decrease (by 22-25%) in the rate of deamination of benzylamine and 4-nitrobenzylamine was found in blood sera of the patients. PMID- 3088836 TI - [Biochemical mechanisms of prostaglandin synthetase co-oxidation of xenobiotics (review)]. PMID- 3088837 TI - [Circulating immune complexes in patients with malignant neoplasms]. AB - Circulating immune complexes were identified in 143 patients with malignant tumors (70--solid cancer, 37--acute leukemia, 21--chronic lympholeukemia and 15- myelomatosis) as well as in 64 patients with chronic inflammatory diseases. Immune complexes were detected in 40% with the aid of precipitation with polyethylene glycol alone and in 50%--by using it in combination with an anticomplementary method. Immune complexes occurred more often in acute myeloid leukemia (66%) than in pancreatic cancer (23%) or chronic lymphoid leukemia (29%). The immunoglobulin profile of complexes varied: in patients with pancreatic cancer, mainly IgM was found; in leukemic patients--different combinations of IgM, IgA and IgG. In the immune complexes of some patients with pancreatic disease, CEA and normal pancreatic antigens were detected. PMID- 3088838 TI - [Characteristics of bacteria shedding among patients with destructive pulmonary tuberculosis]. PMID- 3088840 TI - Puyallup Medical Clinic self-determines health care for Indian clients. PMID- 3088839 TI - [Glycoproteins of enveloped animal viruses as transmembrane proteins]. PMID- 3088841 TI - Screening flexible sigmoidoscopy by primary care physicians. Effectiveness and costs in patients negative for fecal occult blood. AB - A total of 252 consecutive screening flexible sigmoidoscopies were done by two community-based general internists on asymptomatic patients with stool negative for occult blood. Neoplastic lesions were found in 26 patients (10.3%), including 27 adenomatous polyps, 2 with carcinoma-in-situ and 1 carcinoid tumor. No complications resulted from flexible sigmoidoscopy. Nineteen patients with positive screening sigmoidoscopy underwent colonoscopy, and additional adenomatous polyps were found in six patients (31.6%), but no additional malignancy. Total cost for screening flexible sigmoidoscopy and additional studies was $30,359 ($1,168 per patient with a polyp or malignancy and $10,119 per patient with a malignant lesion). Screening flexible sigmoidoscopy can be safely done by community-based general internists in asymptomatic patients with a diagnostic yield comparable with that reported by subspecialists; total costs are acceptable. PMID- 3088842 TI - [Primary bladder calculi in children]. PMID- 3088843 TI - [Treatment of herpes recurrens with a carbon dioxide and acetone paste]. PMID- 3088844 TI - [Incorrect treatment of patients with allergic disorders]. PMID- 3088845 TI - [Evaluation of fetal maturity indices in pregnancy with Rh isoimmunization treated with a preparation of Lasolvan]. PMID- 3088846 TI - [Combined radio- and chemotherapy of anal cancer]. AB - The treatment regime in anal carcinoma is changing from being a mainly surgical problem. Combined radio-chemotherapy is of increasing interest as treatment of choice. The new treatment modality, including chemotherapy with Mitomycin C and 5 fluorouracil combined with percutaneous and interstitial radiotherapy is presented. The treatment regimes performed at the University Department for Radiotherapy and Radiobiology Vienna is discussed with regard to tolerance, side effects and local control. PMID- 3088847 TI - Recent advances in preservation of viable corneal tissue. AB - Increasing numbers of preserved corneas are being transplanted as the demand for optimal bioavailability for donor corneas increases. McCarey-Kaufman (MK) short term storage provides a sufficient endothelial cell viability for a maximum of only 4 days. Organ culture of corneoscleral discs extends post mortem storage times up to 4 weeks. K-Sol, a new cornea storage medium with 2.5% chondroitin sulfate, containing no calf serum as source of foreign protein and no dextran as artificial dehydrating agent, permits tissue to be used for at least 2 weeks after enucleation stored at 4 degrees C. The corneal endothelium was intact, as demonstrated by subsequent vital staining and phase microscope evaluation. Pachymetric measurements showed regular thinning profiles in 31 K-Sol preserved corneas for corneal transplantation, with a clear outcome after a preliminary average observation time of six months. PMID- 3088848 TI - [Acute respiratory failure]. AB - The acute respiratory insufficiency (ARI) is a complicating syndrome in many severe, primarily not the lungs affecting internal and chirurgical diseases. As result of activation of classic cascade-systems, gas diffusion disturbance, right left shunt and lung restriction occur. The effecting global respiratory insufficiency is only to prevent by polypragmatic therapy but often lung fibrosis terminates medical efforts. PMID- 3088850 TI - Current status of heart and lung transplantation. PMID- 3088851 TI - Rapid turnover proteins as nutritional indicators. PMID- 3088849 TI - Prospects for pancreatic islet transplantation. PMID- 3088852 TI - Nodular goiter: effects of surgery and thyroxine medication. PMID- 3088853 TI - Sugar alcohols and dental health. PMID- 3088854 TI - The problem of food and nutrition in Africa. PMID- 3088856 TI - [Increase in the effectiveness of basic funds in public health and social service]. PMID- 3088855 TI - Protein-energy malnutrition (Kwashiorkor-Marasmus syndrome): terminology, classification and evolution. PMID- 3088857 TI - [Status and perspectives of the protein supply of the human]. PMID- 3088858 TI - [Rioprostil 600 micrograms at night: marked inhibition of nocturnal intragastric acidity in man]. AB - Antisecretory doses of prostaglandin analogues of the E1 and E2 series have been shown to promote peptic ulcer healing. In this double blind randomized cross-over study we investigated the effect of oral Rioprostil 300 micrograms b.i.d., 600 micrograms hs and placebo on 24 h intragastric H+ activity in 9 healthy male volunteers (age 20-37 years). 5-10 ml of gastric contents were aspirated hourly via a nasogastric tube. The pH of the samples was determined using a glass electrode . The results were expressed in terms of H+ activity (mmol/l). Night acidity (AUC/h, 2400-0800) is decreased by rioprostil in a dose related fashion (300 micrograms: 52%, 600 micrograms: 74%). The effect on day-time (0900-1800) H+ activity is much less. Rioprostil 300 micrograms given at breakfast reduce day time acidity by 33%. Our results suggest that 600 micrograms Rioprostil in a single bedtime dose is effective in peptic ulcer treatment. PMID- 3088859 TI - [Stomach ulcer healing with enprostil, an orally effective prostaglandin E2 analog: direct comparative study with ranitidine]. AB - In a randomized, endoscopically controlled double-blind trial the effectiveness of a twice daily dose of the prostaglandin E2-analogue enprostil was compared with ranitidine given to 93 ambulatory patients with benign gastric ulcers. Under 35 micrograms b.i.d. enprostil the ulcer healing rates after 2, 4, 6 and 8 weeks averaged 22% (10/46), 58% (26/45), 80% (35/44) and 86% (37/43). The corresponding values for ranitidine 150 mg b.i.d. were 22% (10/46), 66% (29/44), 84% (38/45) and 89% (41/46). The differences were not statistically significant. Both drugs had a similar influence on the ulcer symptoms and were well tolerated. The findings suggest that enprostil can be given in a twice daily dosage in the treatment of benign gastric ulcers. PMID- 3088860 TI - [Enprostil in the acute treatment of duodenal ulcer: direct comparative study with pirenzepin]. AB - In a randomized, endoscopically controlled double-blind trial the effectiveness of a twice daily dose of the prostaglandin E2-analogue enprostil was compared with pirenzepine given to 97 ambulatory patients with duodenal ulcers. Under 35 micrograms b.i.d. enprostil the ulcer healing rates after 2, 4 and 6 weeks averaged 41%, 82% and 92%. The corresponding values for pirenzepine were 44%, 72% and 89%. The differences were not statistically significant. Both drugs had a similar influence on the ulcer symptoms. PMID- 3088862 TI - Advances in the biochemistry and pathophysiology of pepsin 1. PMID- 3088861 TI - [Effect of hyperosmolar glycerol, mannitol and sorbitol solutions on kidney function]. AB - Changes of the renal function of a three-phase course originate from the application of hypertonic infusions. The first phase is characterized by a copious osmotic diuresis and the decrease of the re-absorption of osmotic free water. The second phase shows a lower osmotic diuresis and the re-absorption of osmotic free water attains the values before the beginning of the infusion. The third phase produces a urine time volume like before the infusion, however, the re-absorption of osmotic free water exceeds the starting-value. A biphasic course with isotonic electrolyte infusion is opposed to the three-phase course with osmotic load. Changes of the osmolarity in plasma and urine is to be recommended in order to take it into consideration more in the clinical practice. PMID- 3088863 TI - [A standardized method for the quantitative determination of apolipoprotein AI in serum using immunoturbidimetry measured with the Specol photometer]. PMID- 3088865 TI - [Microprecipitation in agarose gel as a detection method for C-reactive protein in human serum]. PMID- 3088864 TI - [Comparative studies of peroxidase, alkaline phosphatase and beta-galactosidase as marker enzymes. Insertion into a colorimetric and fluorimetric enzyme immunoassay in IgG-conjugated form]. PMID- 3088866 TI - Clot-selective thrombolysis: the impact of tissue-type plasminogen activator (t PA) in thromboembolic diseases. PMID- 3088867 TI - [The functional system as a methodologic principle of the knowledge of the adaptive behavior of man and animals]. PMID- 3088868 TI - [Membrane mechanisms of the development of gonococci to antibiotics]. PMID- 3088869 TI - [Artificial feeding methods in maxillofacial patients]. PMID- 3088870 TI - [New aspects of the pathogenesis of acromegaly-somatoliberinomas]. AB - According to modern knowledge, acromegaly can develop in at least three ways. A pituitary adenoma with growth hormone overproduction is the most frequent. Much rarer is ectopic growth hormone secretion by extra-hypophyseal tumors. A further possibility is the production of growth hormone releasing factor (GRF) by hypothalamic or ectopic tumors. This involves the secretion of a substance which selectively stimulates the GH producing cells of the pituitary. Special features of the clinical and morphological picture of this condition are described, based on the authors own observations. Two patients developed acromegaly: one had a retroperitoneal paraganglioma and the other a bronchial carcinoid. Ectopic GRF secretion could be confirmed radioimmunologically and immunohistologically in both cases. As a result of the on-going, tumor related GRF stimulation the patients developed nodular or diffuse GH-cell hyperplasia in the adenohypophysis. Since ectopic GH secretion does not cause hyperplasia of the adenohypophyseal cells, morphologic examination of the hypophysis can contribute to the differential diagnosis in such cases. PMID- 3088871 TI - [Comparative study of the detection of Pseudomonas aeruginosa in water]. AB - In this report we examined quantitatively (MPN-procedure) various methods of isolating Ps. aeruginosa from surface waters. When comparing different media (malachitgreen broth, Preuss-broth, selenite broth, asparagine broth, malachitgreen/acetamide broth) the enrichments in malachitgreen and asparagine showed the highest isolation frequencies after an 48 h incubation time. In heavily polluted river water the results can be improved by a second enrichment step in acetamide broth. Dependent on the river water pollution 0...11,000 Ps. aeruginosa/l were detected. In waste water up to 2.4 X 10(6) Ps. aeruginosa/l were isolated. The results emphasize the significance of water as a reservoir and a source of distribution of Ps. aeruginosa in the environment. PMID- 3088872 TI - [Assessment of nutritional status for surgical planning]. AB - 72 patients with gastro-intestinal carcinomas were involved in a retrospective study in which 97 metabolic parameters were pre-operatively determined from each of them and subsequently tested by stepwise discriminant analysis for their bearings on clinical mortality. A discriminant function of seven parameters was obtained and can be used as a prognostic nutritional index for successful subdivision of patients into differentiated risk groups. Two prospective control studies were conducted into 605 patients consecutively operated on for benign and malignant diseases for the purpose of testing the nutritional index for its prognostic information potential. The discriminant function proved to be applicable to differentiation between patients with high, moderate, and low surgical risk. Findings were unambiguous. The nutritional index can thus be used as an aid for decision-making in cases in which alternatives exist between several surgical approaches. The importance of malnutrition as a possible causative factor of complications is likely to grow along with the invasiveness of the intervention. PMID- 3088873 TI - [Pancreatic donor operation for islet cell isolation and transplantation]. AB - Preservation of B-cells, following organ collection and cold ischaemia, was defined on 19 donor organs by means of histological tests and testing for insulin content in pancreatic tissue. The degree of preservation declined by 50 per cent after two hours of cold ischaemia. The Velcro technique and uncrushed organ digestion were used for isolation. Islet yield was calculated by determination of insulin levels in isolated tissue (nmol/ml) and in the islet (pmol/islet). The average islet yield was 2 076 islets to one gram pancreas, that is ten per cent of the original amount. Studies conducted into in-vitro insulin secretion from isolated islets have revealed damage to organs due to handling, especially to organs which had undergone extended cold ischaemia. PMID- 3088874 TI - [Hereditary resistance to anthrax and sensitivity to the anthrax toxin in mice]. AB - The degree of the hereditary susceptibility of mice to anthrax caused by noncapsular and capsule-forming Bacillus anthracis strains has been found to be directly related to the sensitivity of the animals to the edematogenic and immunosuppressing action of anthrax toxin. The genetic analysis indicates that resistance to anthrax is probably controlled by a dominant gene, not linked with histocompatibility complex H-2 and, probably, unrelated to the presence of hemolytic activity in mouse sera, determined by component C5 of the complement. PMID- 3088875 TI - [Hospital infection due to Pseudomonas aeruginosa in resuscitation departments]. AB - The bacteriological survey of resuscitation and intensive care units has revealed the presence of P. aeruginosa strains in the microflora in 69.4% of cases. The circulation of 1-2 P. aeruginosa strains, identical in their serovar and pyocin type, is indicative of the presence of hospital infection and, therefore, the endogenous character of the contamination of patients. P. aeruginosa hospital strains are the main causative agents of infectious complications in the patients treated in resuscitation units. PMID- 3088876 TI - [Combined parenteral and enteral nutrition in multiple injuries]. PMID- 3088877 TI - Jejunal diverticula causing massive haemorrhage. AB - Two elderly patients with massive bleeding from jejunal diverticulosis are reported. Scintigraphy revealed the bleeding source. Emergency resection of the involved portion of jejunum cured the patients. Few such cases have been published. Although very rare, one must always have in mind jejunal diverticula to be the source of gastrointestinal haemorrhage. PMID- 3088878 TI - Polydioxanone in anastomosis of rabbit tubes. A morphological study of the epithelium. AB - Eight NZW rabbits were submitted to end-to-end tubal anastomosis using polydioxanone (PDS), (Ethicon). The animals were sacrificed at two-week intervals between the second and sixteenth week after operating. The tubes were removed and analysed with the scanning electron microscope for the purpose of studying the morphology of the epithelium. Ciliogenesis was completed between the second and fourth weeks. After this period the epithelial conditions observed were completely normal, except for an abundant mucous secretion which, however, was totally normal after sixteen weeks. PMID- 3088879 TI - Evan's syndrome, chronic active hepatitis and focal glomerulonephritis in IgA deficiency. AB - A 10-year-old female with a complete selective IgA deficiency and recurrent autoimmune disease (chronic active hepatitis, focal glomerulonephritis, hemolytic anemia and thrombopenic purpura) is presented. Both serum IgA and saliva secretory IgA were below the detection limit. The small bowel biopsy using a peroxidase-antiperoxidase technique showed absence of plasma cells secreting IgA. Circulating antibodies against mitochondria, microsomal thyroid antigen were detected as well as rheumatoid factor. Circulating immune complexes were present. A positive Coombs' test and a slightly positive reaction for cryoagglutinins were demonstrated. No alterations in cellular immunity were observed. Clinical and analytical improvement with prednisone and azathioprine was obtained. PMID- 3088880 TI - Incidence of TdT positivity in cases of leukemia and lymphoma. AB - The expression of the enzyme marker terminal deoxynucleotidyl transferase (TdT) was examined by immunofluorescence assay in the cells from 333 cases with various types and subtypes of leukemia or lymphoma. More than 90% of cALL and T-ALL, 70% of Null-ALL and 80% of pre-B-ALL were TdT-positive. One case in the commonly TdT negative group of B-ALL showed TdT-positive cells. All cases of mature B-cell malignancies (B-CLL, hairy cell leukemia, B-cell lymphoma) have been TdT negative. In the group of mature T-cell malignancies, T-CLL and mycosis fungoides were negative and 2 out of 6 mature T-cell lymphomas were TdT-positive. 13% of acute myeloid leukemias and 36% of CML in blast crisis expressed TdT. Therefore, these TdT-positive cases of CML in blast crisis also carrying the common ALL antigen belong to the lymphoid subtype. CML and erythroleukemia were invariably TdT-negative. TdT has become an indispensable indicator of immature lymphoid leukemia cells and is particularly valuable as part of the panel of markers used in leukemia phenotyping. PMID- 3088881 TI - Circulating committed and pluripotent haemopoietic progenitor cells, in infants. AB - Circulating CFU-GM, BFU-E and CFU-MIX were assayed in 21 infants aged between 1 day and 44 weeks. Compared to 15 adults, progenitor cells of all types were increased until 10 weeks following birth and approached the respective ranges of adults thereafter. The mean increases of progenitor cells in infants aged between 1 day and 10 weeks were 26-fold for CFU-GM, 7-fold for BFU-E and 5-fold for CFU MIX. Our results demonstrate that not only committed progenitor cells (CFU-GM, BFU-E), but also early progenitor cells with the capacity for self-renewal (CFU MIX), are increased in early infancy. These data further support the hypothesis that high levels of blood progenitor cells in very early stages of life reflect the colonization process of developing bone marrow by circulating progenitor cells and demonstrate the terminal phase of this process during the first 10 weeks after birth. PMID- 3088882 TI - A new chromosome translocation (3;21) in M2 acute lymphocytic leukemia. AB - High-resolution chromosome banding studies were carried out on leukemic cells from a young patient with acute nonlymphocytic leukemia (ANLL), M2 of the FAB classification. A new chromosomal abnormality involving a translocation between chromosomes 3 and 21 was observed, i.e., t(3;21)(p14;q22). A complete remission was never obtained in spite of aggressive chemotherapy and the patient died 8 months after diagnosis. PMID- 3088883 TI - Distribution of Gc protein (vitamin D binding protein) on the surfaces of normal human lymphocytes and leukemic lymphocytes. AB - Distribution of membrane-bound Gc protein (mGc) in normal lymphocyte subpopulations and leukemic lymphocytes was studied using a rabbit antiserum specific to Gc protein. Forty to fifty percent of the normal peripheral blood mononuclear cells were stained with anti-Gc antiserum by membrane immunofluorescence, and almost all of the B cells (B1+) and NK cells (Leu 11+) were mGc-positive. Only a few resting T cells (T3+) reacted with anti-Gc, but mGc appeared in a significant number of the T cells after activation by PHA. The distribution of mGc on leukemic lymphocytes of various types nearly corresponded to that in normal lymphocyte subpopulations. PMID- 3088884 TI - Effects of blood storage on red cell antioxidative systems. AB - The activities of the antioxidative enzymes superoxide dismutase, catalase and glutathione peroxidase and the concentration of reduced glutathione were determined in CPD-adenine blood stored at 4 degrees C for up to 20 days. Superoxide dismutase activity was found to be significantly reduced with storage beyond 10 days. The clinical significance of this finding is discussed. PMID- 3088885 TI - Acute myelofibrosis with associated intracerebral haemorrhage. AB - The case of a 42-year-old woman with clinical and histopathological features suggesting acute myelofibrosis is reported. The patient succumbed to massive intracerebral haemorrhage. PMID- 3088886 TI - A case of leukemic mastocytoma terminating in metamorphosis. AB - A case of leukemic mastocytoma terminating in metamorphosis is reported. Three types of mastocytoma cells appeared in the peripheral blood and bone marrow, each differing in cytochemical staining and maturation ability in both in vitro and in vivo cultures. Most immature mastocytoma cells, which contained no granules and were lymphoblast-like cells, differentiated to have basophilic and metachromatically positive granules in the cytoplasm after culture in the diffusion chamber, resembling more mature cells (type II). Mature cells (type II), which had diffusely dispersed and metachromatically positive granules in the cytoplasm, came to have vacuoles with basophilic substances after culture in vitro, resembling most mature cells (type I) which contained large and clumped granules with metachromasia. These findings together with clinical findings and results of morphological studies suggest that most immature cells originate from second mature or most mature cells and effect a blastic transformation. PMID- 3088887 TI - High-dose intravenous corticosteroid treatment in childhood idiopathic myelofibrosis. AB - Two cases of idiopathic myelofibrosis of childhood were treated with intravenous methylprednisolone. A complete improvement of hematological and clinical findings was achieved. PMID- 3088888 TI - Adult T-ALL related to transitional cortical-medullary thymocytes with surface markers of the CD4 subset. AB - This report describes a case of adult T-acute lymphoblastic leukemia. Leukemic blast cells of this patient displayed a rare intermediate cortical-medullary phenotype (E-sheep+, OKT3-, OKT6+, OKT9+, OKT10+, OKT11+) with features of the CD4 subset (OKT4+, OKT8-, Fc mu+, Fc gamma-). PMID- 3088889 TI - Congenital heterozygous plasminogen deficiency associated with a severe thrombotic tendency. AB - Heterozygous plasminogen deficiency was found in 2 patients (mother and daughter). The mother, aged 55 years, was symptomatic while the daughter, aged 10 years, was asymptomatic so far. The thrombotic tendency presented by the proposita (mother) was severe and included recurrent superficial, portal, mesenteric, subclavian thrombophlebitis. No arterial thrombosis was noted. Oral anticoagulants have been of some benefit. The main laboratory features were: plasminogen activity about 50% of normal in two amidolytic methods and in a caseinolytic method. Plasminogen antigen was also about 50% of normal using electroimmunoassay and radial immunodiffusion. Crossed immunoelectrophoresis revealed a normal, even though reduced pattern, thus excluding dysplasminogenemia. Routine coagulation tests were negative. Euglobulin lysis time, fibrinogen level and fibrinogen degradation products (FDP) were within normal limits. Antithrombin III, protein C and protein S were also within normal limits. PMID- 3088890 TI - Tentative and updated classification of factor X variants. PMID- 3088892 TI - Lymphocyte subpopulations in sickle-cell anemia. PMID- 3088891 TI - Increased collagen synthesis of bone marrow fibroblasts by materials released from platelets of chronic granulocytic leukemia and polycythemia vera. AB - Collagen synthesis stimulated by materials released from platelets (MRFP) of patients with chronic granulocytic leukemia (CGL) and polycythemia vera (PV) was measured in human bone marrow fibroblasts derived from normal individuals. The MRFP of patients with CGL and PV stimulated normal fibroblast collagen synthesis significantly compared to the response from normal MRFP. Platelets derived from patients with CGL and PV may have some factors that dramatically stimulate collagen synthesis which is relevant to the frequently observed myelofibrosis in these diseases. PMID- 3088893 TI - Different bindings to lectin in human submandibular gland after enzymatic digestion. AB - Lectin binding affinities were described in human submandibular gland (SMG) in the paraffin sections following alpha-amylase, sialidase, and trypsin digestions. Lectins in the present study were used Con A (Glc, Man binding lectins), PNA, and SBA(Gal, GalNAc), RCA-1(Gal), DBA(GalNAc), WGA(GlcNAc), and UEA-1(Fuc). Lectin stainings in serous and mucous acinar cells and ductal epithelia were reported to compare enzyme treated and nontreated sections. Amylase treatment showed increasing Con A staining in connective tissue fibers and no marked changes in SMG to lectin bindings. Sialidase digestion was characteristically intense in PNA and SBA bindings in SMG cells, and also enhanced staining to UEA-1 in serous and duct cells and to WGA in mucous and duct cells were noted. Trypsin digestion indicated a slight increase to Con A binding, and was relatively strong to UEA-1 in serous and duct cells and a little strong to WGA. The results suggested that SMG serous cells contain higher amounts of Gal, GalNAc, and Fuc residues; and mucous cells were also abundant in Gal, GalNAc, and GlcNAc residues. PMID- 3088894 TI - Interaction of mistletoe lectin I with Kupffer cells and endothelial cells of mouse liver. AB - The in vitro-formation of blebs by endothelial and Kupffer cells of the mouse liver after treatment with the toxic lectin I from mistletoe are demonstrated by means of scanning electron microscopy. The interaction of toxic lectins with nonparenchymal liver cells can be of importance concerning the elimination of these lectins in vivo. PMID- 3088895 TI - The heterogeneity of the nucleus raphes dorsalis in albino rats. A fluorescence histochemical and microelectrophoretic study. AB - In albino rats, the nucleus raphes dorsalis (NRD) of the midbrain was investigated using a sensitive fluorochroming procedure to detect indolamines in combination with a microelectrophoretic method to demonstrate the isoenzyme pattern of acetylcholinesterase (AChE). Based on the fluorescence histochemical appearance, 3 types of indolaminergic cells were identified in the various areas of the NRD. According to data of the literature and in agreement with our own results, the morphological heterogeneity of the NRD was shown. Significant differences of AChE specific zymograms of NRD regions (subgroups) demonstrate that organization of NRD is heterogeneously proved not only by morphological results but also in respect of enzyme constitution. PMID- 3088896 TI - Glycoprotein composition of olfactory mucus in vertebrates. AB - Acid water-soluble glycoproteins of olfactory mucus in various representatives of the vertebrate have been studied. Olfactory mucus of these representatives is found to be of great similarity in its glycoprotein composition. The universal presence of these glycoprotein components of the mucus is supposed to testify to their similar functional significance in various vertebrates. PMID- 3088897 TI - Evaluation of localization and intensity of the reactions of succinic dehydrogenase, NADH tetrazole reductase, and lactate dehydrogenase in developing rat testis. II: After cadmium chloride treatment. AB - The described experiments showed the influence of a single dose of cadmium chloride (1.5 mg CdCl2/kg body mass) applied intraperitoneally on the activity of succinic dehydrogenase (SDH), NADH tetrazole reductase (NADH-R), and lactate dehydrogenase (LDH) in the rat's male gonad. It was ascertained that disturbances of the reaction begin to occur in the 7th d of post-fetal life: they increase gradually, first at the circumference and then the centre of the organ reaching their maximum in 1.5 year old rats. PMID- 3088898 TI - Lability to acid hydrolysis in some different DNA-protein complexes of spermatozoa. AB - The Feulgen hydrolysis kinetics was investigated in spermatozoa with different composition in DNA-protein complexes. The species used were: Bos taurus (arginine rich nuclear protein also containing cystine residues), Pichroplus bergi, Triatoma infestans (arginine-rich nuclear protein), Lytechinus variegatus and Apis mellifera (lysine-rich nuclear protein). The spermatozoa were subjected to Feulgen's reaction, after varying the fixative type and the hydrolysis times. Feulgen-DNA values were obtained with an automatic scanning cytophotometric procedure. Differences were demonstrated in the hydrolysis kinetics as a function of differences in composition of the DNA-protein complexes being present in the spermatozoon chromatin. Differences in the profiles of Feulgen hydrolysis curves, having for basis the fixation, were rather clear for bull, grasshopper, and blood sucking insect spermatozoa than for the sea-urchin and bee spermatozoa. The different hydrolysis kinetics of chromatin of blood-sucking insect spermatozoa compared to that of grasshopper, sea-urchin, and bee sperm cells suggests that, although the first 2 materials contain an arginine-rich "germinative" protein and the latter 2 ones contain a lysine-rich protein, these differ to each other. The DNA depurination was obtained more quickly for T. infestans (20 min) and P. bergi (10 min) spermatozoa when they were fixed in the ethanol-acetic acid (EA) mixture. Morphologically anomalous bull spermatozoa fixed in the EA mixture presented a quicker depurination (30 min) as compared to the normal cells (1 h). The fast lability to acid hydrolysis in the abnormal cells is certainly due to anomalies in their basic nuclear "germinative" protein. In the formalin fixed materials the maximal depurination was obtained earlier in bull spermatozoa (30 min) followed by sperm cells of P. bergi, T. infestans, L. variegatus (all of them one-hour hydrolysis) and finally Apis mellifera (2 h hydrolysis). The presence of secondary peaks at the descending branch of the hydrolysis curves of grasshopper and sea-urchin spermatozoa, indicates for these, more than 1 kind of apurinic-acid protein complexes. The spermatozoa bearing arginine-and/or cystine rich nuclear protein contain a more easily soluble apurinic acid protein complex. Due to the differences in hydrolysis kinetics of chromatin in spermatozoa containing different nuclear "germinative" proteins, this cellular type does not appear indicated as a haploid control for evaluation of Feulgen-DNA contents of diploid and polyploid somatic cells. PMID- 3088899 TI - [Acid cysteine proteinase inhibitor (cystatin A) in reticulum cells of malignant lymphogranulomatosis. A contribution to the development of specific cell types in this disease]. PMID- 3088900 TI - [Detection of muscarinic receptors on cultivated endothelial cells]. AB - In order to contribute to the verification of the hypothesis of Furchgott et al. that the effect of acetylcholine on blood vessels is mediated by factors produced by endothelial cells, the authors tried to provide evidence for the existence of muscarinic receptors on these cells. Using cultivated cells of the endothelium of calve aortas, a specific saturable binding of the potent muscarinic antagonist 3H Quinuclidinyl benzilate and therewith the existence of muscarinic receptors on the cells could be demonstrated. Long time cultivation leads to the disappearance of the receptors. PMID- 3088901 TI - The pharmacological effect of thyrotropin-releasing hormone on ataxic mutant mice. AB - The Rolling mouse Nagoya (RMN), Staggerer, Weaver and Reeler, all of which show hereditary ataxia, were intraperitoneally injected with 25 mg/kg of thyrotropin releasing hormone (TRH-T) or physiological saline, and changes in the motions of these animals were observed by an Animex II and an open field method. All four strains of mice with ataxia showed improvement of ataxia and an increase in the motion volume, but these changes were not necessarily consistent in degree. Improvement of ataxia was most marked in the RMN and the Staggerer, moderate in the Weaver and slight in the Reeler, which showed enhanced tremor. The relationship between the competence of transmitting information in the cerebellum and improvement of ataxia by the injection of TRH-T aroused our interest. PMID- 3088902 TI - A comparison between regional cerebral blood flow measurements obtained in human subjects using 11C-methylalbumin microspheres, the C15O2 steady-state method, and positron emission tomography. AB - Regional cerebral blood flow (rCBF) values were measured in nine normotensive subjects with known previous myocardial infarctions using 15 mu 11C-methylalbumin microspheres and positron emission tomography (PET). Microspheres were injected directly into the left ventricle of each subject during routine cardiac angiography and blood flow calibrated using the reference sample technique. rCBF values were compared with those obtained for a group of fifteen age-matched normal controls using the C15O2 steady-state inhalation technique. Using 1 cm radius circular regions of interest, the 11C-microspheres approach yielded mean blood flow values of 51 ml/100 ml/min and 48 ml/100 ml/min for regions of interest dominated by temporal and frontal cortical grey matter respectively. An rCBF value of 32 ml/100 ml/min was obtained for regions of interest dominated by frontal white matter. Mean rCBF values obtained for these regions using the C15O2 method were not significantly different (52 ml/100 ml/min, 44 ml/100 ml/min, and 28 ml/100 ml/min respectively), but the C15O2 approach gave a significantly lower rCBF value than the 11C-microspheresfor regions of interest dominated by occipital grey matter. Although the two groups of subjects studied were not strictly equivalent, the good agreement between blood flow values obtained using the 11C-microspheres and the C15O2 techniques is of interest, and suggests that the assumptions of the C15O2 steady-state approach do not lead to large errors in practice. PMID- 3088903 TI - Glioblastoma with sarcomatous component associated with myxoid change. A histochemical, immunohistochemical and electron microscopic study. AB - The case of a 22-year-old female suffering from glioblastoma with sarcomatous component (WHO; gliosarcoma) is presented. The tumor consisted of glioblastomatous and sarcomatouos components, and in part of the pleomorphic astrocytomatous region of the glioblastoma there was a prominent production of myxoid matrix. On the basis of its histochemical and immunohistochemical characteristics, the present case strongly suggested that glial cells of neuroectodermal origin assume part of the responsibility for production of myxoid material. PMID- 3088904 TI - Effects of different extraction media on the electrophoretic pattern of proteins from partly mineralized bovine enamel. AB - Five different extraction solutions were used to isolate matrix proteins from immature bovine enamel, to evaluate the effect of this procedure on the pattern obtained after electrophoresis. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the dominating protein fraction in the ethylenediaminetetraacetic acid extract had a molecular weight of 67,000 daltons. The acetic acid and phosphate buffer extracts contained mostly low molecular weight proteins. Isoelectric focusing showed that most of the enamel proteins had isoelectric points below pH 7.0. PMID- 3088905 TI - Growth hormone therapy of short stature. AB - Considerable progress has been made in the diagnosis and treatment of growth hormone-related short stature. Knowledge about growth hormone releasing factor (GRF) and somatomedin C has provided the possibility of distinguishing between hypothalamic and pituitary growth hormone deficiency and growth hormone resistance. It has been shown that treatment with GRF may stimulate growth in certain cases of growth hormone deficiency. Recombinant DNA techniques may, in the near future, provide sufficient amounts of GRF, growth hormone and possibly somatomedin C for clinical use. At present, many countries have prohibited the use of human pituitary growth hormone due to a possible risk of transmission of Creutzfeldt-Jakob disease. It has become increasingly clear that several short children without classical growth hormone deficiency, may increase their growth velocity during growth hormone treatment. There are many medical, psychological, ethical and economical implications involved in the extended treatment of children with short stature. It is necessary to maintain a restricted approach towards the treatment of children with short stature, and such treatment should be prescribed and controlled by a limited number of well-trained paediatric endocrinologists. This article reviews some of the present knowledge in this rapid developing field of paediatric endocrinology. PMID- 3088906 TI - Alterations of urinary carbon dioxide tension, electrolyte handling and low molecular weight protein excretion in acute pyelonephritis. AB - Renal tubular function tests were performed in 45 children suffering from upper and lower urinary tract infections. Determinations were made of the urinary carbon dioxide tension in maximally alkaline urine as an index of distal tubular H+-ion secretion, of urinary protein excretion, and of urinary sodium and phosphate handling. Urinary PCO2 was low (2.7 +/- 13.9 mmHg) in acute pyelonephritis compared to values in healthy children (52 +/- 32 mmHg) or those with cystitis (48 +/- 34 mmHg). At the onset of pyelonephritis an elevated fractional excretion of sodium (1.38 +/- 0.38 vs. 0.50 +/- 0.20%) and decreased phosphate reabsorption (69.2 +/- 7.1 vs. 90.4 +/- 4.9%) were also observed. Significantly elevated urinary low molecular weight protein excretion was also found in pyelonephritis. These data indicate the existence of proximal and distal tubular dysfunction at the onset of acute bacterial pyelonephritis. PMID- 3088907 TI - Hyperkalemic distal renal tubular acidosis in salt-losing congenital adrenal hyperplasia. AB - Functional indices of distal urinary acidification were assessed in two male infants, aged 1 and 3 months, with salt-losing congenital adrenal hyperplasia. In both cases the diagnosis was sustained by the presence of elevated plasma levels of 17-hydroxyprogesterone, hyponatremia, hyperkalemia, metabolic acidosis and increased plasma renin activity. Both patients were unable to lower urinary pH below 5.9 either during acute ammonium chloride-induced acidosis or after i.v. administration of furosemide. One patient also failed to decrease urine pH below 5.5 and to increase urinary potassium excretion during sodium sulfate infusion. Oral sodium bicarbonate loading was given to both patients but failed to induce a significant increase in the urine minus blood PCO2 gradient. This gradient remained low also after neutral phosphate administration. Repeated studies after acute administration of fludrocortisone in one case or after prolonged administration of hydrocortisone in the other resulted in complete normalization of all functional studies. We conclude that salt-losing congenital adrenal hyperplasia can lead to hyperkalemic distal renal tubular acidosis in early infancy. The defective renal secretion of hydrogen ion and potassium is probably related to the abolishment of the negative potential difference in the cortical collecting tubule induced by the impaired reabsorption of sodium. PMID- 3088908 TI - Transcutaneous oxygen and carbon dioxide levels and a clinical symptom scale for monitoring the acute asthmatic state in infants and young children. AB - Measurement of transcutaneous PO2 and PCO2 in addition to a clinical symptom grading system was used to monitor the acute asthmatic attack in children under two years of age. tcPO2 was lowered already at signs of mild obstruction and decreased in parallel with clinical deterioration. tcPCO2 was almost unchanged at mild to moderate obstructive symptoms. With clinical deterioration tcPCO2 rose steadily. An increase of the oxygen concentration to 30-40% in the inspired air increased tcPO2, on the average by 70%, but did not change the tcPCO2, level. Continuous recording of tcPO2 and tcPCO2 as well as the clinical grading system are valuable tools when monitoring severely obstructive infants and young children. PMID- 3088909 TI - Related bindings of aggregated beta 2-microglobulin, IgG Fab, kappa and lambda light chains to group A streptococci. AB - Aggregates of various mammalian beta 2-microglobulin (beta 2m) homologues were tested in binding experiments with group A streptococcal strains of different M types. The binding patterns obtained were similar, suggesting that evolutionarily conserved parts of the beta 2m molecule are responsible for the interaction with group A streptococci. An N-terminally abnormal beta 2m showed binding characteristics similar to those of normal human beta 2m, indicating that the amino-terminal does not participate in this interaction. Aggregates of human IgG Fab fragments, kappa chains and lambda chains, were also analyzed. Whereas several of the beta 2m-reactive M types did not interact with any of these aggregates, all strains binding aggregated Fab, kappa or lambda, also bound aggregated beta 2m. Strains of M types 4, 12, 23 and 53 bound all the tested proteins; M type 1 bound all but IgG Fab, whereas M types 46, 49 and 53 showed affinity for beta 2m and lambda chains only. In inhibition experiments, unlabelled aggregated beta 2m in excess completely blocked the uptake of radiolabelled aggregated IgG Fab, kappa and lambda chains. Conversely, Fab, kappa and lambda aggregates inhibited the binding of radiolabelled beta 2m aggregates. Our results indicate that the differences in reactivity recorded between beta 2m and IgG Fab, kappa and lambda chains, all structurally related, are quantitative rather than qualitative. Thus, a common binding structure for these aggregated proteins on group A streptococci appears probable. PMID- 3088910 TI - Pseudomonas aeruginosa virulence factors: modifications by sub-inhibitory concentrations of carbenicillin or gentamicin. AB - A virulent strain of Pseudomonas aeruginosa was assayed for adhesion to HEp-2 cells, production of toxin A, and production of elastase, in the presence of sub inhibitory concentrations of carbenicillin and gentamicin. Both antibiotics, assayed in a concentration of 1:12 of their minimum bactericidal concentration (MBC), inhibited the production of toxin A. Gentamicin at this concentration totally abolished the production of elastase, whereas carbenicillin had little or no effect on this factor. Both antibiotics inhibited the bacterial adhesion, but in different ways. While gentamicin had a strong activity of slow onset, carbenicillin had a transitory activity of rapid onset, with return towards normal values after 90 min incubation. PMID- 3088911 TI - Two separate non-immune interactions between staphylococcal protein A and immunoglobulins are mediated by structures on gamma chains. AB - The present investigation was undertaken to determine whether the light or the heavy immunoglobulin chain is involved in the alternative, non-immune F(ab')2 mediated binding to staphylococcal protein A. Purified human polyclonal IgG was mildly reduced with dithiothreitol and alkylated with iodoacetamide. Intact IgG, purified light and heavy chains of polyclonal immunoglobulin G were tested in an inhibition assay for alternative non-immune F(ab')2-mediated binding to the protein A-carrying S. aureus, strain Cowan I. The IgG Fc-mediated binding to protein A was studied in parallel inhibition experiments. Heavy chains inhibited both the alternative F(ab')2- and the classical Fc-mediated binding to protein A. Isolated light chains were non-reactive. Intact IgG molecules were more potent inhibitors than isolated heavy chains tested in equimolar concentrations. Our results indicate that the alternative non-immune interaction between staphylococcal protein A and human immunoglobulins is mediated by structures expressed on the heavy immunoglobulin G chain. Thus, there are two separate protein A binding sites on gamma chains. PMID- 3088912 TI - The effect of ergotamine on the arterial system in man. PMID- 3088913 TI - Measurement of respiratory water loss in newborn lambs. AB - A flow-through system for measurement of respiratory water loss, providing data on oxygen consumption and carbon dioxide production, is described. The system uses a mass spectrometer, specially equipped with a water channel, for analysis of gas concentrations. To avoid condensation of water vapour, the tubing in the flow-through system is heated. The method was tested by evaporating known amounts of water, and was found to be very accurate with a correlation coefficient of 0.999. Measurements were made in 10 fullterm lambs of varying postnatal age (4-15 days) and a mean respiratory water loss (RWL) of 11.7 mg kg-1 min-1 was found at rest. The RWL decreased with increasing postnatal age, as did oxygen consumption. The RWL at rest was influenced by the ambient relative humidity, with higher values at lower humidities. PMID- 3088914 TI - Indacrinone (MK-196)--a specific inhibitor of the voltage-dependent Cl- permeability in toad skin. AB - The effect of indacrinone (MK-196) on Cl- transport through toad (Bufo bufo) skin epithelium was studied by the voltage clamping technique. At the transepithelial potential, V = 50 mV (serosal bath grounded) the unidirectional fluxes, governed by a Cl- self-exchange diffusion pathway, were not affected by 1 mM racemic MK 196 in the outer bath. Likewise at V = o mV, the unidirectional fluxes as well as the active (net) inward flux of Cl- were unaffected by MK-196. Voltage clamping the epithelium in the physiological range of potentials activated a Cl- specific passive conductance that saturated for V less than or equal to -90 mV. The influx and efflux of Cl- through this pathway were inhibited by MK-196, and the (passive) Cl- current was inhibited in a dose-dependent way for [MK-196] greater than or equal to 50 microM with about 70% inhibition for [MK-196] = 1 mM. The maximum Cl- conductance was decreased without shifting the position along the V axis of the inverted S-shaped conductance-voltage relationship. The time constants for the voltage-stimulated Cl- conductance activation were not affected by MK-196 (50 microM less than or equals [MK-196] less than or equals 1 mM). The (+) and (-) isomers and racemic MK-196 affected the voltage-dependent Cl- conductance in similar ways. It is concluded that MK-196 has the properties of a Cl- channel blocker which is specific for the voltage-dependent Cl- permeability of the epithelium. The time course for development of inhibition exhibited a fast (min) and a slow (h) component.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3088915 TI - Comparison of PGE2, 6-keto PGF1 alpha and renin release from dog kidneys. AB - Several renal cell types synthesize prostaglandin E2 (PGE2) and prostacyclin (PGI2). To examine whether the release of these prostaglandins varies in proportion, prostaglandin synthesis was stimulated in anaesthetized dogs by renal arterial constriction, ureteral occlusion, intrarenal angiotensin II infusion and infusion of arachidonic acid, the precursor of PG synthesis. PGI2 was measured as its stable hydrolysed product, 6-keto PGF1 alpha. The two former procedures raised PGE2 release to 13 +/- 2 pmol min-1, 6-keto PGF1 alpha release to 5 +/- 2 pmol min-1 and renin release to 23 +/- 5 micrograms AI min-1. Angiotensin II infusion, reducing the renal blood flow by 30%, increased PGE2 and 6-keto PGF1 alpha release only half as much as ureteral and renal arterial constriction, and exerted no significant effect on renin release. By increasing the infusion rate of angiotensin II up to 10 times, the renal blood flow remained unaltered in four dogs and fell to 50% of control in two dogs, but PGE2 and 6-keto PGF1 alpha release did not increase further in any of the experiments. Arachidonic acid, infused at 40 and 160 micrograms kg-1 min-1, increased prostaglandin release in proportion to the infusion rate. At the highest infusion rate, PGE2 release averaged 166 +/- 37 pmol min-1 and 6-keto PGF1 alpha release 98 +/- 28 pmol min 1. All procedures increased PGE2 and 6-keto PGF1 alpha release in a fixed proportion of about 2.5:1, whereas renin release increased only during autoregulatory vasodilation. PMID- 3088916 TI - The management of resistant depression. AB - Between 10 and 30% of depressed patients, mostly bipolar, develop a therapy resistant illness. The known causes of such chronic evolutions are discussed: misdiagnosis (underlying schizophrenia, personality disorder or dementia), drug induced depression (neuroleptics), systemic disease (hypothyroidism, multiple sclerosis, cardiovascular or neoplastic disease etc.), or lack of efficacy (drug compliance, insufficient dosage). Remedies are suggested: adequate dosage, drug combination (Newcastle cocktail. tricyclic antidepressant + MAOI, imipramine + T3), carbamazepine in lithium-resistant cases, alprazolam, reduction in vanadium intake, sleep deprivation, psychosurgery. PMID- 3088917 TI - Basal TSH determination instead of TRH test. PMID- 3088918 TI - Immunopurinogenic enzymatic activity in the acquired immunodeficiency syndrome. PMID- 3088920 TI - The stabilization of ascorbic acid by uric acid. PMID- 3088919 TI - Comparison of surface differentiation antigens between HGPRT-positive and negative T-cells from two Lesch-Nyhan heterozygotes. PMID- 3088921 TI - Erythrocyte GTP depletion in PNP deficiency presenting with haemolytic anaemia and hypouricaemia. PMID- 3088922 TI - Changes in lymphocyte adenosine deaminase and purine nucleoside phosphorylase levels in lung cancer after radical surgery. PMID- 3088923 TI - Dipyridamole and 8-aminoguanosine inhibition of nucleoside metabolism in rat blood in vitro. PMID- 3088924 TI - Effect of high altitude and acetazolamide on human serum and urine purines. PMID- 3088925 TI - The effect of lipoxygenase inhibitors and leukotriene antagonists on anaphylaxis. AB - The experiments whose results are reported here were carried out with the aim of showing a possible role for lipoxygenase products in the modulation of the Schultz-Dale reaction. For this purpose, the actions of nordihydroguaieretic acid (NDGA) and of FPL 55712 were tested during anaphylaxis in guinea-pig ileum and trachea in vitro. Isolated preparations from guinea-pigs, which had been subcutaneously sensitized with ovalbumin and incomplete Freund adjuvant, were challenged with increasing concentrations of antigen; in preparations isolated from the same animal an antigen-concentration anaphylactic-reaction curve was performed in the presence of the drugs. NDGA 3.3 X 10(-6) M was capable of inhibiting anaphylaxis in the trachea to a maximum extent of 40% but it did not affect anaphylactic reaction in the intestinal smooth muscle. FPL 55712 2 X 10( 6) M did not exert any activity on anaphylaxis in either preparations. The difference between SRS-A and histamine as mediators of anaphylaxis in the tissue preparations used could explain the fact that NDGA acted on the trachea alone. PMID- 3088926 TI - Diamine oxidase as a marker of intestinal integrity in acute appendicitis. AB - In the operative treatment of appendicitis the so called negative appendectomy is an important issue because of its increased morbidity. From the hypothesis that the intestinal diamine oxidase activity is a suitable marker of mucosal integrity, the distribution pattern of the enzyme in appendices histologically classified as inflamed or not inflamed was studied. Histologically apparent inflammation of the appendix was connected with a significant reduction of diamine oxidase activity. The determination of this enzymic activity may be a simple and sensitive test for mucosal inflammation of the appendix even at a very early state. This could reduce the rate of negative appendectomies and influence thereby risk-cost-benefit calculations. PMID- 3088928 TI - Diamine oxidase (DAO) and female sex hormones. AB - DAO activity in tissues of female guinea pigs was determined after the administration of estradiol or progesterone. Estradiol pretreatment elicited significant fall in DAO activity in the liver and specific increase in the uterus. The effect of progesterone was much less pronounced. PMID- 3088927 TI - Diamine oxidase activity in Japanese quail liver induced with aroclor 1254. AB - Male adult quails were treated with a single intraperitoneal dose of Aroclor 1254 mg/kg. The animals showed increases in hepatic weight and benzopyrene hydroxylase activity which were continuous up to 168 h after the treatment. At 96 h after treatment the activity of diamine oxidase (DAO) in the microsomal fraction was significantly decreased whereas that of spermidine synthase seemed to increase. PMID- 3088929 TI - Guanabenz as inhibitor of copper-containing amine oxidases. AB - The effects of guanabenz on some copper containing amine oxidases are described. Guanabenz 'in vitro' inhibits pig plasma benzylamine oxidase with a IC50 M 5.1 +/ 0.8 X 10(-6) M. It also inhibits pig kidney diamine oxidase and rat liver mitochondrial monoamine oxidase at higher concentrations. The significance of this property of guanabenz is discussed. PMID- 3088930 TI - Articular cartilage proteoglycans immunoreactive with an antibody to skin proteodermatan sulfate core protein. PMID- 3088931 TI - Variation with ageing and degeneration of the serine and cysteine proteinase inhibitors of human articular cartilage. AB - The proteoglycans, and proteinase inhibitors of normal and degenerate human articular cartilage have been isolated by 4.0M GuHCl extraction, CsCl density gradient ultracentrifugation and Sephadex G-75 gel filtration chromatography. While a small amount of trypsin inhibitory activity eluted in the Sephadex G-75 void volume, the major proteinase inhibitors were included in the column with MWs within the range 1 - 3 X 10(4) daltons. The large molecular weight trypsin inhibitor was identified as alpha 1-trypsin inhibitor, which was present in greater amounts in degenerate tissue. The Sephadex G75 included fractions (LMWCI) showed inhibition against cysteine and serine proteinases and were reduced in degenerate tissue, but slightly elevated in aged "normal" cartilage. We suggest that the resistance of ageing cartilage to enzymatic degradation may be related to the levels of LMWCI within these tissues. PMID- 3088932 TI - Amplification of oxyradicals by eicosanoid synthesis. PMID- 3088933 TI - Leukoencephalopathy in normal and pathologic aging: 1. CT of brain lucencies. AB - Central white matter lucencies are commonly seen in CT scans of elderly patients. Reports in the literature have implicated demyelination due to subcortical vascular disease (Binswanger disease) as the cause of these lucencies. Binswanger disease, however, is thought to be rare. Because of this apparent discrepancy we decided to determine the incidence and to attempt to define the clinical significance of the CT white-matter changes in a study population at New York University Medical Center. The studies of 275 normal and demented subjects, ages 23 to 85 years, were reviewed. All subjects received neurologic, psychiatric, and medical evaluation, formal psychometric evaluation of their cognitive status, and a CT scan. CT scans were evaluated for the presence and severity of white-matter changes (leukoencephalopathy). The incidence and severity of white-matter changes increased significantly with age (p less than 0.01). Leukoencephalopathy was consistently more common in demented patients than in normal subjects, but the difference was not statistically significant, and the severity of the leukoencephalopathy was not related to the severity of dementia (p less than 0.05). Five patients (ages 74 to 95 years) with a clinical diagnosis of Alzheimer disease who had CT evidence of lucencies were examined at autopsy. Neuropathology demonstrated extensive changes of Alzheimer disease in one brain and mild-to moderate changes in the other four brains; areas of white-matter rarefaction were present in all brains, with microscopic evidence of arteriolar hyalinization. This study demonstrates that leukoencephalopathy is strongly related to the aging process and is seen in both "normal" and cognitively impaired individuals who have no other evidence of vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3088934 TI - Leukoencephalopathy in normal and pathologic aging: 2. MRI of brain lucencies. AB - A pilot study was performed to test the ability of MR to evaluate the brain lucencies shown by CT in Alzheimer disease patients and in normal control subjects. Eight patients with presumed Alzheimer disease and 47 normal controls, 12 over the age of 45 years and 35 under age 45, were studied. Each group included subjects with and without CT evidence of leukoencephalopathy. Inversion recovery, saturation recovery, and spin-echo scans were obtained using a 0.3-T permanent magnet prototype unit. Results indicated that MR was more sensitive than CT to parenchymal disease. Seven of the eight patients with Alzheimer disease showed patches of increased signal intensity on SE scans; only three had lucencies on their CT studies. None of the normal subjects under the age of 45 showed periventricular patches of increased SE signal intensity. T2-weighted SE imaging was performed in nine of the 12 normal subjects over 45 years old. Eight of the nine demonstrated periventricular patches of increased SE signal intensity. Faint CT lucencies were present in only one of these. The configuration of the patches of increased signal intensity was similar for both the normal and Alzheimer groups, but the extent of white-matter involvement was greater in the Alzheimer group. PMID- 3088935 TI - MR demonstration of altered cerebrospinal fluid flow by obstructive lesions. AB - We investigated the MR imaging appearance of flowing cerebrospinal fluid (CSF) in the brain in the presence of obstructive lesions of the ventricular pathways. The pulsatile movement of CSF through the ventricular system is seen as an area of low signal intensity that has been termed the CSF flow-void sign (CFVS). This is best appreciated in areas of narrowing within the ventricular system; that is, the aqueduct of Sylvius, foramen of Magendie, and interventricular foramina. MR studies of 27 patients with lesions affecting the ventricular pathways were reviewed for the presence of the CFVS. Single-echo T1-weighted and T2-weighted multisection techniques were used in all cases. The CFVS was always seen more prominently on the T2-weighted images. The presence of the CFVS indicated patency of the ventricular pathway in which it was identified. The absence of the CFVS in the presence of hydrocephalus indicated that a possible obstructive lesion was present, but it did not directly indicate the level of the obstruction. The CFVS was absent in the aqueduct of Sylvius in 13 patients with obstruction or stenosis of the aqueduct, but it was also absent in one patient with a colloid cyst of the interventricular foramina. In three patients with preoperative and postoperative MR, the CFVS was seen in the area of interest only after resection of the obstructing lesion. We concluded that the presence of the CFVS is a useful indicator of the patency of the ventricular pathway in which it is seen. The absence of the CFVS at a location in which it is normally seen may indicate the presence of an obstruction, but it must be correlated with other signs to be interpreted correctly. PMID- 3088936 TI - High-field MRI of hemorrhagic cortical infarction. AB - High-field MRI is capable of differentiating acute, subacute, and chronic hemorrhagic cortical infarctions. In eight of nine patients, hemorrhage occurred in a vascular watershed zone. Acute hemorrhagic cortical infarction produces mild cortical low intensity on T2-weighted images outlined by subcortical edema (high intensity) and isointensity with normal cortex on T1-weighted images. Subacute hemorrhagic cortical infarction shows cortical high intensity first on T1 weighted images and later on T2-weighted images; it is also associated with subcortical edema. In the chronic stage, there is a marked persistent cortical low intensity on T2-weighted images. This is most prominent in the deeply infolded cortical gyri. The low intensity noted in acute and chronic hemorrhagic cortical infarction with T2 weighting appears to be related to two separate underlying histochemical states. The characteristic cortical low intensity observed on T2-weighted images in acute and chronic hemorrhagic cortical infarction is proportional to the square of the magnetic field strength. PMID- 3088937 TI - MRI of central nervous system: early clinical results. AB - In patients with central nervous system problems, a comparison of the results obtained with high-field MRI (1.5 T) to those achieved with more conventional imaging studies, primarily CT, reveals significant improvement in the demonstration of various abnormalities by MRI (56.5%), with increased specificity in some (29.5%). High-field MRI provides advantages over CT by providing both multiplanar images and superior contrast resolution. The diagnostic specificity of MRI is increased when acute, subacute, and chronic hematomas are visualized and when flowing blood within vessels is demonstrated in addition to the location and extent of the disease process. In this series, MRI produced a more accurate diagnosis in 8.7% of cases, revealed clinically unexpected abnormalities in 3.9% of cases, and was less invasive or avoided the risk of complications in 17.4% of cases. Despite the success of MRI, CT continues to play an important role in demonstrating calcification and contrast enhancement, and in evaluating patients in whom MRI is contraindicated or impossible because of an unsuitable clinical state. PMID- 3088938 TI - MRI of the central nervous system in neonates and young children. AB - Twelve normal neonates and young children, ages 32 weeks gestation to 20 months, and 22 abnormal children up to four years old had MRI scans using a 0.5 T superconducting scanner. A faint signal that was presumed to be myelin was detected in the thalami at 32 weeks; myelination of the occipital lobes was present at full term, and visible throughout the hemispheres by 8 weeks of age. Anatomical locations of congenital lesions were well demonstrated, especially in sagittal views. The signal changes of perinatal abnormalities, such as hemorrhage and hemiatrophy, were often specific. Abnormal position of the spinal cord, spinal lipomas, and other congenital lesions were also well visualized. PMID- 3088939 TI - MRI of corpus callosal syndromes. AB - Six patients, 6 to 13 years old, with corpus callosal abnormalities diagnosed by electroencephalography or CT were studied with a 0.15 T MR imager to determine the effectiveness of MRI in evaluating midline anomalies. Spin-echo images in the coronal, axial, and sagittal planes were obtained in two patients with Aicardi's syndrome and partial agenesis of the corpus callosum, in one patient with Dandy Walker syndrome, and in two patients with septooptic dysplasia. Inversion recovery and spin-echo images were obtained in one patient with lipoma of the corpus callosum. Partial agenesis of the corpus callosum was seen in septooptic dysplasia, an association that has not been reported previously in the radiologic literature. Direct sagittal and coronal MRI provided better anatomic visualization of the brain and ventricles than did reformatted CT. T1-weighted images are sufficient to diagnose and delineate the extent of midline cerebral abnormalities. The unique capability of direct sagittal imaging makes MRI the best procedure for evaluating corpus callosal and other midline abnormalities. PMID- 3088940 TI - CT and MR of angiomatous malformations of the choroid plexus in patients with Sturge-Weber disease. AB - Eight patients with Sturge-Weber disease were evaluated by CT (six patients), MR (one patient), or both (one patient). CT scans of five of seven patients showed enlargement and increased enhancement of the choroid plexus on the same side as the facial and intracranial lesions. MRI showed similar findings in both patients examined. This enlargement, seen in six of eight cases of Sturge-Weber disease, is compatible with the presence of angiomatous malformations of the choroid plexus. It appears to be a common finding in this disease. PMID- 3088942 TI - CT in diagnosis of acoustic neuromas. AB - A detailed analysis of the CT findings in 75 cases of acoustic neuroma is presented. The method of examination included plain and enhanced CT, metrizamide CT cisternography (M-CTC), and gas CT cisternography (gas-CTC). The common CT appearances of acoustic neuromas were as follows: 93.6% appeared as isodense or hypodense on precontrast scan; homogeneous enhancement was observed in 53.8% on postcontrast scan; the tumor center, mostly located at the level of the internal acoustic canal, was spherical in shape with an acute angle between the lateral tumor border and petrous bone; and there was widening of the internal acoustic canal or destruction of petrous bone. However, the presence of an acoustic neuroma could not be excluded if widening of the internal acoustic canal was absent. It was not certain whether contrast filling of the internal acoustic canal occurred at M-CTC in the four cases so examined. One case of intracanalicular neuroma was diagnosed by gas-CTC, which is the most sensitive and reliable technique for detecting and excluding small tumors. The significance of various CT appearances, early diagnosis, and differential diagnosis of acoustic neuroma from other cerebellopontine-angle tumors, particularly meningioma, are discussed. PMID- 3088941 TI - MR and CT in cytoplasmically inherited striatal degeneration. AB - A rare, cytoplasmically inherited striatal degeneration associated with Leber's optic atrophy exhibited selective symmetric low-density lesions in the putamen on the CT scan in five patients. The CT findings, however, were asymmetric (one patient) and subtle in the early phases of the disease. Occasionally, caudate lesions were demonstrable. On MR imaging, the lesions had high signal intensity on T2-weighted images and low signal intensity on T1-weighted images. This group of patients was distinguished from patients with other causes of striatal degeneration by a lack of hemispheric, brainstem, or cerebellar atrophy. PMID- 3088943 TI - Ophthalmopathy of Graves' disease: computerized volume measurements of the orbital fat and muscle. AB - Pixel-calibrated volume measurements of muscle and fat in the bony orbit were made from CT scans of 72 patients with Graves' disease, with and without ophthalmopathy, to define characteristic changes present in clinical subgroups. Measurement abnormalities were detected in 87% of Graves' patients with clinically detectable ophthalmopathy and in 70% of hyperthyroid patients without clinical eye signs. Abnormal enlargement of the fat compartment in addition to muscle enlargement was found in 46% of patients with clinical ophthalmopathy; 8% of patients had only increased size of the fat compartment with normal muscle volumes. The ratio of muscle to fat and the volumes of orbital muscle and fat all varied widely in each clinical subgroup. Statistically significant (p less than 0.0001) total muscle-volume increase (range = 3.68-17.06 cm3) and borderline significant (p less than 0.06) fat-compartment increase (range = 6.05-22.63 cm3) were documented in all clinical subgroups. The degree of change of muscle and fat volumes was independent of the clinical group. Abnormal changes were found in the contralateral orbit in six of seven patients who appeared to have unilateral ophthalmopathy on clinical examination. A higher frequency of medial and inferior muscle enlargement was documented in all clinical subgroups. PMID- 3088944 TI - Rare presentations of ordinary lipomas of the head and neck: a review. AB - The ordinary lipoma is the most common neoplasm of mesenchymal origin. Only 13% of them arise in the head and neck region and most of these occur subcutaneously in the posterior neck. Rarely, they can develop in the anterior neck, infratemporal fossa, and in or around the oral cavity, pharynx, larynx, and parotid gland. Clinically, they can be confused with other benign lesions; however, CT allows a specific diagnosis to be made in virtually all cases. This article reviews the CT appearance and differential diagnoses of lipomas in these rare locations and discusses the rare infiltrating lipoma and the relationship between parotid lipomatosis and sialosis. PMID- 3088945 TI - Radiation exposure from conventional and digital subtraction angiography of cerebral vessels. AB - Patients with atherosclerotic cerebrovascular disease were studied to determine the radiation exposure associated with conventional and digital subtraction angiography of the cerebral vessels. The median exposure-area product was 3198 R cm2 (range, 616-5665 R cm2) in the conventional angiography group and 1831 R cm2 (range, 366-4198 R cm2) in the IV digital subtraction angiography (DSA) group. This difference in exposure resulted from increased use of fluoroscopy in the conventional screen-film angiography group. The actual difference in exposure between the radiographic and digital imaging portions of the examinations was much smaller. The contributions of fluoroscopy to the radiation exposure in conventional angiography and IV-DSA in this study were 37% (range, 8.8-76%) and 6% (range, 1.5-25%), respectively. PMID- 3088946 TI - The application of i.v. digital subtraction angiography to cranial disease in children. AB - All intracranial IV digital subtraction angiographic examinations performed over the past 2 years were reviewed retrospectively to ascertain the uses and limitations of this technique for the evaluation of pediatric intracranial disease. Of the various abnormalities studied, this imaging technique was particularly useful in diagnosing venous and dural sinus abnormalities; in screening for suspected large aneurysms, vascular malformations, and major arterial occlusive disease; and in preoperative vascular mapping. IV digital subtraction angiography has selected usefulness in confirming brain death, in evaluating cerebral ischemia, in identifying vascular abnormalities underlying intracranial hemorrhage, and in evaluating vascularity and sinus extension of masses. The IV route for digital subtraction angiography is not useful in diagnosing segmental arterial occlusive or small-vessel disease, nor is it useful in preoperative localization of specific arterial supply to arterial venous malformations, aneurysms, or neoplasms. IV digital subtraction angiography can be performed successfully in children of all ages with minimal patient morbidity. For most patients, the diagnostic information obtained was adequate without the need for standard cerebral arteriography. PMID- 3088947 TI - High-dose i.v. contrast in CT scanning of the postoperative lumbar spine. AB - Evaluation of the postoperative lumbar spine is sometimes difficult because of obliteration of epidural fat by hypertrophic scarring. We examined 70 patients using a high-dose intravenous contrast technique in an attempt to distinguish hypertrophic scarring from herniated disk. The CT interpretation was confirmed in all 17 patients who had follow-up operations. Thirteen had herniated disk material associated with scar and four had hypertrophic scarring only. The latter four patients underwent reoperation because of concomitant foraminal or spinal canal stenosis seen on CT. Twelve of the herniated disks had the expected appearance of a nonenhancing mass surrounded by a rim of enhancing scar tissue. In the 13th patient, homogeneous enhancement of the herniated disk was seen. It is thought that chronically herniated disks, such as this one, may incite enough surrounding scar to give the CT appearance of an enhancing disk. Finally, marginal enhancement in the anulus fibrosus region was seen in over 90% of disk spaces examined. Although an anatomical explanation cannot be given at present, this phenomenon is thought to represent a normal finding. PMID- 3088948 TI - Traction device to improve CT imaging of lower cervical spine. PMID- 3088949 TI - Delayed presentation of posttraumatic cervical disk herniation. PMID- 3088951 TI - Neuroradiologic features of primary falx osteosarcoma. PMID- 3088950 TI - Arachnoid cyst of the quadrigeminal plate cistern: report of two cases. PMID- 3088952 TI - MRI of an aneurysm of the vein of Galen. PMID- 3088953 TI - Results of the international extracranial/intracranial arterial bypass: implications for radiologists. PMID- 3088954 TI - CT evaluation of perineural orbital lesions. PMID- 3088955 TI - Prolactinomas after bromocriptine therapy. PMID- 3088956 TI - Diabetes management: an update. AB - The diabetic diet is no longer as rigid as it once was. Oral hypoglycemic agents continue to have a place in management, and the declining cost of human insulin makes it an increasingly attractive option. Home glucose testing is the preferred monitoring method, and its use is becoming more common. Regardless of the management method used, close control offers the potential benefit of fewer diabetic complications but also presents increased hazards from hypoglycemia. PMID- 3088957 TI - The role of transdermal nitroglycerin in the treatment of coronary heart disease. AB - Nitroglycerin has long been a mainstay of the treatment of ischemic cardiac pain. The introduction of transdermal formulations and in particular the development of controlled methods of delivery have been responsible for the renaissance of clinical interest in this simple and effective treatment. The pathophysiologic abnormality accompanying myocardial ischemia affords a natural theater for the exhibition of the therapeutic utility of these preparations and methods. The means whereby nitrates induce relaxation of vascular smooth muscle are not entirely clear, but their pharmacodynamic activities are perfectly plain. In the doses used in clinical practice, nitrates exert their predominant hemodynamic effects and therapeutic benefits through their peripheral vasodilator activities. This is particularly marked in veins, although in higher doses nitrates also dilate the larger systemic and coronary arteries. Criticisms of the efficacy of transdermal formulations of nitrates in the treatment of angina pectoris have arisen largely from uncritical acceptance of a small number of studies of questionable methodologic validity. Large-scale general practice studies have invariably found that transdermal nitrate delivery systems improve the quality of life in ambulant patients: anginal attacks are reduced with a minimum of side effects. The widespread acceptance of this novel form of drug delivery has stimulated its application in other therapeutic avenues. The efficacy of transdermal nitroglycerin in the suppression of silent ischemic attacks has been demonstrated. The maintenance of benefit initiated by intravenous nitroglycerin in patients with unstable angina also broadens the use of this method of nitrate delivery. In patients with acute myocardial infarction, whether complicated by left ventricular failure or not, the nitrates, and transdermal nitroglycerin in particular, appear to hold considerable promise. Improvement of hemodynamic abnormalities may cause reduction in infarct size and fewer life-threatening arrhythmias. Even survival may be extended. The utility of transdermal nitrates in the treatment of severe chronic heart failure is less certain. But the use of higher doses and an interval regimen of administration may hold promise for such patients. Naturally, more information is required before the overall therapeutic profile of this new method of controlled nitroglycerin delivery across the whole spectrum of coronary heart disease can be fully described. Fortunately, the high level of efficacy and safety of transdermal nitroglycerin demonstrated in the majority of reported studies encourages the pursuit of such an important therapeutic target. PMID- 3088958 TI - The controversy over transdermal nitroglycerin: an update. PMID- 3088959 TI - Clinical relevance of nitrate hemodynamic attenuation. PMID- 3088960 TI - Usefulness of intravenous and transdermal nitroglycerin therapy in patients with unstable angina. PMID- 3088961 TI - Mechanisms and therapy of silent myocardial ischemia: the effect of transdermal nitroglycerin. PMID- 3088962 TI - Some issues concerning transdermal nitroglycerin patches. AB - There is sufficient evidence to suggest that the duration of action of transdermal nitroglycerin patches is between 20 and 26 hours, as measured by exercise testing. At 24 hours there may be some patient variability, particularly with lower doses; however, the majority of patients show an increase in exercise time at 24 hours. In studies of the same patients, higher doses of transdermal nitroglycerin resulted in greater increases in exercise time, suggesting that higher doses may be more effective and that titration to higher doses is desirable. However, there is insufficient information from the chronic studies reported in the literature to draw any definitive conclusions. In the only crossover comparative studies reported in the literature to date, transdermal nitroglycerin appears to be as effective as isosorbide dinitrate and nifedipine. While transdermal nitroglycerin patches appear to be an effective mode of therapy, further studies are needed to confirm these findings. PMID- 3088964 TI - Recent studies on transdermal nitroglycerin patch efficacy. PMID- 3088963 TI - A multicenter trial of transdermal nitroglycerin in exercise-induced angina: individual antianginal response after repeated administration. PMID- 3088965 TI - Scientific and clinical experience with transdermal nitroglycerin. Panel discussion. PMID- 3088966 TI - Scientific and clinical experience with transdermal nitroglycerin. Summary and conclusions. PMID- 3088967 TI - Effect of alcohol intake and exercise on plasma high-density lipoprotein cholesterol subfractions and apolipoprotein A-I in women. AB - Abstinence from alcohol consumption for 3 weeks was followed by 3 weeks of wine intake in 18 inactive and 18 physically active premenopausal women (runners). The runners weighed less and had higher plasma high-density lipoprotein (HDL) cholesterol and lower low-density lipoprotein cholesterol levels than the inactive women. There were no differences between groups in plasma total cholesterol, triglyceride and apolipoprotein A-I concentrations. Runners had higher plasma HDL2 cholesterol concentrations than inactive women (34 +/- 17 vs 19 +/- 12 mg/dl), but HDL3 cholesterol concentration did not differ between the groups (41 +/- 10 vs 39 +/- 9 mg/dl). Addition of 35 g/day of ethanol for 3 weeks did not result in a significant change in either group for any of the variables measured. The amount of exercise appears to be a more important determinant of plasma lipoproteins and apolipoprotein A-I than alcohol intake in premenopausal women. PMID- 3088968 TI - Observations of vitamin A toxicity in three patients with renal failure receiving parenteral alimentation. AB - Elevated serum retinol concentrations have been previously reported in patients with renal failure, although overt clinical toxicity has been described only rarely. We present three patients with renal failure receiving total parenteral nutrition (TPN) who developed biochemical and clinical findings of hypervitaminosis A. Improvement followed deletion of vitamin A from the TPN. These cases demonstrate that patients with renal failure may be at risk for symptomatic vitamin A toxicity if given TPN with standard retinol supplementation. Such patients should be carefully observed clinically and biochemically if supplementation is given. PMID- 3088969 TI - Protein nutrition and amino acid metabolism after 4 weeks of total parenteral nutrition with a mixture of 14 dipeptides: serendipitous observations on effects of sepsis in baboons. AB - We investigated parameters of nutrition, metabolism, and organ function after 4 wk of total parenteral nutrition (TPN) in baboons receiving either dipeptides or amino acids as the nitrogen source. The two groups showed no significant difference with respect to gain in body weight, nitrogen balance, plasma and muscle concentrations of amino acids, plasma concentrations of proteins, and leucine incorporation into muscle protein. All dipeptides were efficiently utilized as evidenced by trace concentrations of dipeptides in plasma and urine; they produced no deleterious effect on the function of liver, kidney, or immune system. Development of infection in several baboons increased urinary excretion of urea nitrogen but had no effect on urinary excretion of dipeptides and amino acids with the single exception of taurine, which was greatly increased. In conclusion, the data show long-term efficacy and safety of the dipeptide mixture as the sole nitrogen source for TPN. PMID- 3088970 TI - Enteral-tube feeding as adjunct therapy in malnourished patients with cystic fibrosis: a clinical study and literature review. AB - Eight children (aged 8 mo to 13 yr) with cystic fibrosis (CF) and growth failure were given home nocturnal nasogastric feeding of an elemental diet for 3 mo and re-evaluated 3 mo after cessation of tube feeding. An increase in energy intake (p less than 0.05) resulted in increased serum transferrin (p less than 0.005), retinol-binding protein (p less than 0.05), and clinical scores (p less than 0.05) during the study. Height and growth velocity increased by 60% (p less than 0.05), and weight growth velocity increased by 63%. Arm-muscle circumference, triceps skinfolds, serum albumin, vitamin A, vitamin E, zinc, and copper did not change significantly during tube feeding. Nocturnal feeding were safe and effective in promoting growth; however, most children with severe lung disease did not sustain the gains after cessation of tube feeding. Our findings indicate that continued nutritional support is needed to maintain the growth in malnourished children with severe lung disease. PMID- 3088971 TI - Bone disease in prolonged parenteral nutrition: osteopenia without mineralization defect. AB - A metabolic bone disease characterized by a mineralization defect, low plasma 1,25(OH)2D, and hypercalciuria has been described in patients receiving prolonged total parenteral nutrition (TPN). Because the practice of TPN differs from center to center, we investigated 13 home TPN patients to determine whether they had similar or different bone abnormalities. They had received TPN for a mean period of 51 +/- 38 mo. Bone pain occurred in six patients and two had multiple vertebral and rib fractures (with trauma in one patient). Bone pain was mild to moderate and not incapacitating. Bone histomorphometry showed reduced bone volume, reduced osteoid with normal resorption and calcification rates. These abnormalities were associated with hypercalciuria, but the plasma levels of 1,25(OH)2D were normal. Abnormalities in bone metabolism in this group of patients suggest a fundamental decrease in bone matrix-formation rather than a mineralization defect as the underlying mechanism. PMID- 3088972 TI - Functional anemia of complicated protein-energy malnutrition at high altitude. AB - The effect of severe protein-energy malnutrition (PEM) on erythropoiesis in children living in the highlands of Bolivia, altitude 3700 m, was studied. Forty percent reduced hemoglobin concentrations, significantly lower arterial oxygen tensions, and a right-shifted, oxygen-dissociation curve were observed compared to high-altitude controls. Serum and erythrocyte folate concentrations were 44% and 82%, respectively, of control values. Low initial transferrin saturation decreased significantly during the 10-wk refeeding period. Thus, iron and folate deficiency contributed significantly to the poor red cell response. Results suggest that the anemia associated with severe PEM has a more significant impact on oxygen transport at high altitude than at sea level and requires an adaptive response in the oxygen-dissociation curve to satisfy tissue-oxygen demands. Furthermore, marginal iron and folate status and an inflammatory block of iron supply may limit the reestablishment of a normal tissue mass during refeeding. PMID- 3088973 TI - Transitory stimulation of human platelet 12-lipooxygenase by vitamin E supplementation. AB - Human platelet lipooxygenase converts arachidonic acid to 12-hydroperoxy eicosatetraenoic acid (12-HPETE), which is rapidly reduced by peroxidases to 12 hydroxy-eicosatetraenoic acid (12-HETE). This study was conducted to examine the effect of vitamin E supplementation on platelet 12-lipooxygenase activity. Sixteen healthy subjects were supplemented with 400 IU/day of either D-alpha tocopherol (268 mg) or DL-alpha-tocopherol (364 mg) for 4 wk. Supplements elicited a transitory increase of lipooxygenase activity but a suppression of peroxidase activity, as indicated by increased 12-HETE production and 12-HPETE accumulation. Plasma-tocopherol concentration was double the presupplement value and remained stable during supplementation. Neither age, sex, nor isomeric form of tocopherol supplement significantly influenced the pattern of response. Results show that vitamin E exerts a differential effect on platelet lipooxygenase and peroxidase activities. PMID- 3088974 TI - The efficacy of 5-fluorouracil, mitomycin C, and methyl CCNU in advanced colorectal cancer. AB - Sixty-six patients with advanced colorectal cancer were treated with 5 fluorouracil, Mitomycin C, and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1 nitrosourea. Fifty-seven patients were evaluable by completing 2 months of therapy. Nine patients (16.0%) achieved a complete remission (CR) with the above combination. A partial remission (PR) was seen in 9 patients. The response rate (CR + PR) was 32%. The average duration of response was 8.5 months. Mucositis, leukopenia, and thrombocytopenia were the significant toxicities experienced in this study. PMID- 3088975 TI - Primary large-cell lymphoma of the central nervous system. AB - Primary non-Hodgkin's lymphoma of the central nervous system (CNS) is a rare disease. Seven patients were seen and treated at the University of Michigan Medical Center between January 1969 and December 1983. All patients had histologically proven diagnoses of large cell lymphoma with clinical and radiologic evidence of involvement limited to the CNS. Five of seven patients received postoperative radiation therapy, two of whom have had apparent local control at 1- and 2-year follow-up. The two patients without postoperative radiation died of local recurrence 2 and 3 months following subtotal resection. These poor results suggest that adjuvant therapy may be required for improved control of this type of extranodal lymphoma. PMID- 3088976 TI - Electron beam irradiation after reconstruction with silicone gel implant in breast cancer. AB - Irradiation for breast cancer in the presence of a silicone gel breast prosthesis is sometimes necessary. There is a concern among radiation and other oncologists as to whether the presence of the prosthetic implant would interfere with delivery of the needed irradiation doses. Electron beams, with their finite penetration and rapid fall-off, offer a mode of adequately treating the recurrence and minimizing the radiation to the underlying normal structures, such as the lung and the heart. The dose distribution using 9-20 MeV electrons in the presence of a breast prosthesis is compared to the dose distribution without the implant in a tissue equivalent water phantom. The results reveal no significant difference in the dose delivered due to the presence of the prosthesis. Clinical verification of the dosimetry in the presence of the prosthesis confirmed that the presence of the silicone gel implant does not compromise treatment by irradiation in the management of breast cancer. PMID- 3088977 TI - Diffuse large-cell lymphoma with monoclonal IgM kappa and cold agglutinin. AB - A patient with diffuse large-cell lymphoma associated with a serum monoclonal IgM kappa and a cold agglutinin is described. The cold agglutinin was the initial manifestation of disease and was apparent for at least two months before the diagnosis of lymphoma. The lymphoma cells had surface and cytoplasmic IgM kappa. PMID- 3088978 TI - Objective substitute for accurate measurement. PMID- 3088979 TI - Further observations concerning MPV measurements. PMID- 3088980 TI - Leu-M1 antigen expression in advanced (tumor) stage mycosis fungoides. AB - The authors describe two patients with clinically and histopathologically documented advanced (tumor) stage mycosis fungoides. In each case the large, pleomorphic neoplastic cells lacked the monoclonal antibody-defined cell surface antigens commonly associated with immature and mature T-cells, i.e., T11, Leu-1, T3, T4, T6, T8, and T10, but expressed various T-cell-associated activation antigens, such as HLA-DR, Tac, and T21. Leu-M1, a monocyte-associated antigen, was not expressed by the small, cerebriform neoplastic cells in the plaque stage lesions of either patient. However, Leu-M1 was expressed by most of the large, pleomorphic neoplastic cells present in the nodular lesions of both patients. The pattern of Leu-M1 antigen expression was identical to that previously reported in the Reed-Sternberg cells of Hodgkin's disease. Identification of these two patients suggests using caution in the interpretation of the results of immunophenotypic analysis of cutaneous lymphoid neoplasms and that Leu-M1 should not be used as a diagnostic indicator of Hodgkin's disease or a histiocytic derived neoplasm. These studies also suggest that Leu-M1 may be preferentially expressed on a subpopulation of activated, rapidly proliferating, and/or dedifferentiated neoplastic T-cells that proliferate in the advanced (tumor) stages of mycosis fungoides. PMID- 3088981 TI - Multicenter clinical trial and laboratory utilization of an enzymatic detection method for gonococcal antigens. AB - Seven institutions participated in a comparative study evaluating standard culture method and a new enzyme immunoassay (EIA, Gonozyme, Abbott Diagnostics) for the detection of Neisseria gonorrhoeae. Five hundred twenty-three patients were entered from hospitals of various sizes representing different population densities, ethnic and economic sectors, and gonococcal prevalence. Statistical analysis showed sensitivity, specificity, and positive and negative predictive values of 80.3%, 94.6%, 66.2%, and 97.3% for the total population tested. For the high-prevalence (greater than 15%) population the respective values were as follows: 78.6%, 91.5%, 68.8%, and 94.7%. Specimens from females had a lower sensitivity than those from males. In the low-prevalence population (less than 10%) results were as follows: 100%, 97.8%, 50%, and 100%. A cost comparison emphasized the benefit of the Gram's stain and culture. It also indicated that, unless batched or assayed at high volume, Gonozyme is not cost competitive for laboratories using standard culture methods. The impact of the EIA method, in general, and Gonozyme, specifically, on the microbiology section also was investigated. Integration would require altering of established work patterns and loss of flexibility and freedom of standard plating technics. The fact that Gonozyme is a "presumptive" test limits it to being a complementary assay, not an alternative. The authors conclude that Gonozyme is optimally suited to a high volume laboratory, screening a low-prevalence female outpatient population, where specimen transport is a problem and gonococcal resistance to penicillin has not been demonstrated. This would include sexually transmitted disease clinics, reference laboratories, and state health departments. PMID- 3088982 TI - Neuron-specific enolase and Leu-7 immunoreactive small round-cell neoplasm. The relationship to Ewing's sarcoma in bone and soft tissue. AB - The authors present an immunohistochemical analysis of tissue from five cases of morphologically distinctive Ewing's sarcoma in bone and soft tissue. The mean age of the five patients was 16.6 years, with a range of 6-28 years. The tumors existed in chest wall, pelvis, and lower extremities. Two siblings with tumor in bone were clinically diagnosed as having Ewing's sarcoma. All cases had immunoreactivity for neuron-specific enolase (NSE), and four cases revealed positive staining for Leu-7. Neuron-specific enolase is highly specific for neurons and neuroendocrine cells. In addition, immunoreactivity for Leu-7, expressing a natural killer activity, has been demonstrated in peripheral nerve fibers and neuroendocrine cells. The authors suggest that NSE and Leu-7 immunoreactive small round-cell neoplasm is probably a primitive neuroectodermal tumor and should be categorized as Ewing's sarcoma in bone and soft tissue. PMID- 3088983 TI - Septic atrial thrombosis. A potentially lethal complication of Broviac catheters in infants. AB - Even though the use of Silastic catheters for long-term parenteral nutrition has decreased the incidence of catheter-related thrombosis and infection, these serious complications still occur. We describe three infants with septic atrial thrombosis secondary to use of Broviac catheters. One of the infants had pulmonary embolism and Budd-Chiari syndrome. The use of echocardiography in the diagnosis of this potentially fatal complication and aggressive treatment--which included open heart removal of thrombi--are discussed. The three infants recovered fully from this complication. PMID- 3088984 TI - Assessment of exposure to indoor air contaminants from combustion sources: methodology and application. AB - A methodology for assessing indoor air pollutant exposures is presented, with specific application to unvented combustion by-products. This paper describes the method as applied to a study of acute respiratory illness associated with the use of unvented kerosene space heaters in 333 residences in the New Haven, Connecticut, area from September 1982 to April 1983. The protocol serves as a prototype for a nested design of exposure assessment which could be applied to large-scale field studies of indoor air contaminant levels. Questionnaires, secondary records, and several methods of air monitoring offer a reliable method of estimating environmental exposures for assessing associations with health effects at a reasonable cost. Indoor to outdoor ratios of NO2 concentrations were found to be 0.58 +/- 0.31 for residences without known sources of NO2. Levels of NO2 were found to be comparable for homes with a kerosene heater only and those with a gas cooking stove only. Homes with a kerosene heater and a gas stove had average two-week NO2 levels approximately double those with only one source. Presence of tobacco smokers had a small but significant impact on indoor NO2 levels. Two-week average levels of indoor NO2 were found to be excellent predictors of total personal NO2 exposure for a small sample of adults. Residences with kerosene space heaters had SO2 levels corresponding to the number of hours of heater use and the sulfur content of the fuel. Formaldehyde levels were found to be low and not related to unvented combustion sources. NO2, SO2, and CO2 levels measured in some of the residences were found to exceed those levels specified in current national health standards. PMID- 3088985 TI - Re: "Randomized vs. historical clinical trials: are the benefits worth the cost?". PMID- 3088986 TI - DDAVP in acquired von Willebrand syndrome associated with multiple myeloma. AB - The response to a single intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP, desmopressin) was studied in two patients with acquired von Willebrand syndrome associated with IgG-kappa myeloma. Following infusion of DDAVP (0.3-0.4 micrograms/kg), prolonged bleeding time was normalized; plasma ristocetin cofactor activity, von Willebrand factor antigen, and factor VIII activity were remarkably increased; and high-molecular-weight forms of von Willebrand factor were demonstrated by crossed immunoelectrophoresis in both patients. Excellent hemostasis was achieved following administration of DDAVP in one patient when it was used for the treatment of gum bleeding and for the prophylaxis of bleeding during and after dental extractions. These observations suggest that DDAVP is an effective alternative to blood products for at least some patients with acquired von Willebrand syndrome in addition to patients with inherited von Willebrand disease, hemophilia A, and uremia. PMID- 3088987 TI - Sclerosing encapsulating peritonitis: report of a case with small bowel obstruction managed by long-term home parenteral hyperalimentation, and a review of the literature. AB - Sclerosing peritonitis has recently emerged as a complication of peritoneal dialysis associated with a high morbidity and mortality. These patients experience the characteristic syndrome of nausea, vomiting, abdominal pain, partial small bowel obstruction, and impaired ultrafiltration. A pathologic finding is the replacement of mesothelial cells with a thick layer of nondistensible fibroconnective tissue. We report here a 58-year-old white woman who developed peritoneal sclerosis after 4 years of peritoneal dialysis, including 3 years of continuous ambulatory peritoneal dialysis. Risk factors included peritoneal exposure to low concentrations of formaldehyde and a 1-week exposure to long-dwell acetate dialysate. Laparotomy for partial small bowel obstruction with resection of the involved segment was complicated by enterocutaneous fistulae, which improved only on cessation of oral intake and treatment with home parenteral nutrition. We have reviewed the literature to find 20 cases of sclerosing peritonitis in patients on peritoneal dialysis. A 78% mortality rate is reported in cases that had surgical intervention. We conclude that the use of long-term parenteral nutrition with cessation of oral intake may be necessary in the management of sclerosing encapsulating peritonitis. PMID- 3088988 TI - Multipoint linkage analysis. AB - A formula is given for the advantage of n-point sampling, which approaches infinity with n. However, 2-point and 3-point analyses extract nearly all the information in such samples and at the same time communicate this information as lods and chi 2, which can be combined with other data by simple addition without reevaluation of the likelihood. When null interference is assumed, map distances and multiple recombination frequencies are inflated, and there is substantial loss of efficiency and of support for the correct order. PMID- 3088989 TI - Breakpoint localization of the marker chromosome associated with the cat eye syndrome. AB - We investigated the breakpoints involved in the generation of the supernumerary bisatellited chromosome associated with the Cat Eye syndrome. In situ hybridization of DNA probes from band 22q11 revealed that, for two individuals with the Cat Eye syndrome, both breakpoints for the bisatellited chromosome were distal to the DNA sequence corresponding to probe D22S9 and proximal to the immunoglobulin C lambda genes and to at least one subgroup of the V lambda genes. PMID- 3088990 TI - Production of carbon dioxide gas after reconstitution of ceftazidime. PMID- 3088991 TI - Stability of tryptophan in total parenteral nutrient solutions. PMID- 3088992 TI - Use of a Medicaid database to analyze pharmaceutical services in long-term-care facilities. AB - A profile of Wisconsin pharmacies that provide services to Medicaid recipients in long-term-care facilities (LTCFs) was developed, and the relationships among pharmacy characteristics and drug use and reimbursement for pharmaceutical services in these pharmacies were studied. Computer-generated reports of Medicaid claims of all pharmacies that had received $1000 or more for services provided to LTCFs from July through September 1984 were included in the study; these claims were submitted by 255 pharmacies on behalf of 32,410 recipients. The reports contained the following individual pharmacy data: geographic location, total dollar payments, total number of Medicaid recipients served, percentage of recipients residing in LTCFs, total number of payments from Medicaid for prescriptions, amount paid to the pharmacy for LTCF recipients as a percentage of total payments, percentage of prescriptions paid at the unit dose rate, and average number of prescriptions and cost per LTCF recipient. An average of $137.30 per recipient was reimbursed, representing an average of 12.3 prescriptions per recipient. The average number of prescriptions per recipient did not vary among pharmacies on the basis of unit dose or traditional distribution system, vendor-consultant status of the pharmacist, location of the pharmacy, or the proportion of LTCF claims to total Medicaid prescription claims. The average amount paid per recipient was related to the average number of prescriptions per recipient, the use of a unit dose system, and the proportion of nursing home claims to total claims submitted. A Medicaid database can be useful for characterizing pharmaceutical services and drug use in LTCFs. PMID- 3088993 TI - Home health care: the patient's perspective. PMID- 3088994 TI - Identifying disease-drug cost indicators using diagnosis-related groups. PMID- 3088995 TI - Increased incidence of thyroid disease among men with hypergonadotropic hypogonadism. AB - An association between hypothyroidism and hypogonadism has been described in the syndrome of autoimmune polyglandular failure and in Klinefelter's syndrome. The incidence of thyroid disease among males with hypogonadism was evaluated. Patients were divided into those with hypergonadotropic hypogonadism (Group I; n = 19) and those with isolated hypogonadotropic hypogonadism (Group II; n = 17), according to their serum concentrations of follicle-stimulating hormone, luteinizing hormone, and testosterone. Nine cases of thyroid diseases were encountered in Group I; these included benign and malignant thyroid tumors, hypothyroidism due to Hashimoto's thyroiditis, and hypothyroidism due to amiodarone therapy. Only one case of thyroid disease (hypothyroidism due to Hashimoto's thyroiditis) was found in Group II (p less than 0.01). Patients of Group I were also significantly older than patients of Group II (51 +/- 4 versus 37 +/- 4 years; p less than 0.01); and patients with thyroid diseases were also older than those without thyroid disorders (60 +/- 6 versus 43 +/- 6 years, p less than 0.1). It is concluded that older subjects with hypogonadism and long term elevation of levels of serum gonadotropins should undergo careful evaluation of thyroid gland morphology and function. PMID- 3088996 TI - Light chain myeloma with meningeal and pleural involvement. AB - A 76-year-old woman with newly diagnosed lambda light chain myeloma was found to have involvement of the pleura and meninges. Direct immunofluorescence demonstrated the monoclonal nature of plasma cells found in the pleural fluid; morphologically similar cells were found in the cerebrospinal fluid and bone marrow. Immunoelectrophoresis revealed lambda light chains in the pleural fluid and cerebrospinal fluid, as well as in the serum and urine. Clinically apparent pleural involvement and meningeal involvement by myeloma are each rare events. This is believed to be the first report of both phenomena occurring simultaneously and the first known case of light chain myeloma involving the cerebrospinal fluid. PMID- 3088997 TI - Syndrome of inappropriate antidiuresis in Waldenstrom's macroglobulinemia. AB - Hyponatremia due to the syndrome of inappropriate antidiuresis rather than due to isotonic hyponatremia from hyperproteinemia developed in a patient with Waldenstrom's macroglobulinemia. The patient was unable to excrete a water load normally despite suppression of antidiuretic hormone to normal levels. The temporal relationship between control of the tumor and resolution of the hyponatremia suggests that the tumor either produced a substance that enhanced the hydro-osmotic effect of endogenous antidiuretic hormone or produced an antidiuretic substance immunologically different from antidiuretic hormone. The syndrome of inappropriate antidiuresis should be suspected in hyponatremic patients with Waldenstrom's macroglobulinemia. PMID- 3088998 TI - Aminoglycosides plus beta-lactams against gram-negative organisms. Evaluation of in vitro synergy and chemical interactions. AB - Combination antibiotic therapy has been used mainly to broaden the antibacterial spectrum and prevent the development of resistance. Antibiotic combinations proven to be synergistic in vitro are associated with a significantly better in vivo response, particularly in the compromised host in whom traditional treatment combines an antipseudomonal penicillin plus an aminoglycoside. Several investigators have examined combining new agents, such as the third-generation cephalosporins (cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefoperazone, and moxalactam), aztreonam, or the ureidopenicillins, with amikacin. When compared with combinations of an older cephalosporin, carbenicillin or ticarcillin, plus gentamicin or tobramycin, these newer combinations produce higher rates of clinically meaningful synergy and rapid enhancement of in vitro bactericidal activity against the difficult-to-treat Enterobacteriaceae (i.e., Serratia, Citrobacter, Enterobacter, Providencia, and indole-positive Proteus species). This effect, without any evidence of antagonism, has been reported even for strains moderately or completely resistant to the former antibiotics. Unsatisfactory and unpredictable synergistic interactions against both resistant and susceptible strains of Pseudomonas aeruginosa--the most difficult nosocomial pathogen to treat--have been noted with combinations of tobramycin or gentamicin plus cefotaxime, moxalactam, or cefoperazone. Conversely, the use of amikacin plus various beta-lactams against multi-resistant strains is more frequently synergistic. Agents have been observed to exhibit such synergy in the following order of activity, from most to least synergistic: ceftazidime, ceftriaxone, moxalactam, aztreonam, cefotaxime, azlocillin, cefoperazone, cefsulodin, and carbenicillin. The combination of amikacin plus imipenem or ciprofloxacin against strains of P. aeruginosa resistant to the former and moderately resistant to the latter was recently reported to have a low probability of synergy; the combination of two of the newer beta-lactams had mostly an unpredictable or even antagonistic result. In vitro studies have also demonstrated that high concentrations of the antipseudomonal penicillins can inactivate the aminoglycosides. Among the latter compounds, the inactivation order, from most to least inactivated, was as follows: tobramycin, gentamicin, netilmicin, and amikacin. To date, the reports of aminoglycoside inactivation by the newer cephalosporins have been rather contradictory; only moxalactam has been shown produce a significant decrease in activity. PMID- 3088999 TI - Combination therapy: a way to limit emergence of resistance? AB - The ability of antibiotic combinations to limit the emergence of resistance during therapy was evaluated in a murine model. Peritonitis was produced by injecting a mixture containing 10(8) colony-forming units of bacteria and sterilized talcum into the peritoneum. Two hours later, a single antibiotic dose was administered subcutaneously. The next day, peritoneal bacterial populations were analyzed on Szybalski's gradients. Acquired resistance was recorded when there was at least a fourfold increase in minimum inhibitory concentrations compared with untreated animals. No resistance emerged after amikacin monotherapy (15 mg/kg); however, resistance was frequently observed after monotherapy with ceftriaxone (50 mg/kg) or pefloxacin (25 mg/kg). Resistance to ceftriaxone and pefloxacin emerged, respectively, in 15 percent and 83 percent of animals with Klebsiella pneumoniae, 71 percent and 54 percent with Enterobacter cloacae, 0 percent and 83 percent with Serratia marcescens, 25 percent and 100 percent with Pseudomonas aeruginosa, and 0 percent with both Escherichia coli and Staphylococcus aureus. In mice with K. pneumoniae or E. cloacae infections, any dual combination of amikacin, pefloxacin, and ceftriaxone produced less acquired resistance than did monotherapy. In these animals, the combination of ceftriaxone and pefloxacin abolished all resistance, whereas the combinations of amikacin plus ceftriaxone or amikacin plus pefloxacin reduced the frequency of resistance by more than half. In animals with P. aeruginosa or S. marcescens infections, resistance to pefloxacin diminished or disappeared after treatment with the combinations of pefloxacin plus ceftriaxone or pefloxacin plus amikacin. However, combinations with ceftriaxone resulted in more frequent resistance to ceftriaxone than did ceftriaxone alone. This was the case in P. aeruginosa infections treated with ceftriaxone plus amikacin (p less than 0.01), and in S. marcescens infections treated with ceftriaxone plus pefloxacin (p less than 0.05). Despite these certain notable exceptions, our data confirm that in most cases combination therapy does limit the emergence of resistance. PMID- 3089000 TI - Aminoglycoside resistance: a worldwide perspective. AB - Two concerns, neither of which is particularly new, underlie the current reluctance to use aminoglycosides more broadly. First, an undeniable fact is that these compounds can be toxic, particularly in patients with impaired renal function or those receiving other nephrotoxic medications. Second, a more emotional concern is that widespread use of aminoglycosides, particularly the newer compounds that are more resistant to enzymatic inactivation, may engender widespread resistance. In fact, several sources lead one to doubt whether widespread use of potent and highly effective agents like amikacin will by itself increase a clinical reservoir of more resistant microbes. First, the surveillance studies undertaken in many hospitals show some modest reduction in overall aminoglycoside resistance even when a drug like amikacin is used to supplant antecedent compounds of the same class. Second, in institutions where no official surveillance programs have been undertaken but where ongoing surveillance has been maintained, susceptibility to amikacin has remained constant when recent blood isolates are compared with blood isolates from more than 10 years ago. Third, in controlled clinical trials, particularly in immunocompromised patients, the overall emergence of resistance has been remarkably low and contrasts rather strikingly with what has been observed in some monotherapeutic studies of beta lactam agents. The presence of aminoglycoside-resistant strains cannot be denied, but the circumstances leading to the emergence of such resistance must be carefully assessed, particularly outside of the setting in which these drugs are used as first-line therapy for critically ill patients. For instance, there is substantial evidence to suggest that the topical use of aminoglycosides or the use of these agents when there may be environmental contamination could lead to the emergence of resistance. Before one incriminates the use of any one drug as predisposing to the emergence of resistance, one needs to have more information about the total exposure of a given bacterial population to aminoglycoside therapy. The emergence of resistance to aminoglycosides has been associated with exposure to the more commonly used agents such as gentamicin or tobramycin. With some of the newer beta-lactam agents, the rate of emergence of resistance, unlike that of the aminoglycosides, has appeared to be remarkably high. If the concern about emergence of resistance is genuine, and to maintain consistency of approaches, the infectious disease community should focus more attention on limiting or restricting the use of the more widely used beta-lactam compounds.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3089001 TI - Challenging conventional aminoglycoside dosing regimens. The value of experimental models. AB - Although newer antimicrobials look promising for the treatment of serious gram negative infections, aminoglycosides still remain part of the mainstay of their therapy. Traditional intermittent therapy is based upon the premise that high serum aminoglycoside concentrations are toxic. However, the rate of bacterial killing for aminoglycosides is also a concentration-dependent phenomenon. Two animal models of Pseudomonas pneumonia were utilized to examine the efficacy of non-traditional aminoglycoside dosing regimens, i.e., single, high daily doses versus the conventional, intermittent low doses of aminoglycosides. Other recent data suggest that toxicity might also be less with the large, single daily dose regimen. The current dosing strategy used for aminoglycosides may not be maximizing their therapeutic potential, nor minimizing their toxicities. PMID- 3089002 TI - The potential for discovery and development of improved aminoglycosides. AB - Following the development of amikacin, pharmaceutical companies made intensive efforts to find even more potent and broader-spectrum aminoglycosides. This effort was justifiable in view of the fact that over the preceding decade, these agents, because of their unique properties, had proven to be the primary weapons in the therapeutic armamentarium for the treatment of seriously ill patients. Since the toxicities associated with the aminoglycosides were beginning to limit their use in general medicine, researchers ultimately shifted their emphasis from probing for higher-potency, broader-spectrum agents to finding those with a reduced potential for toxicity. This article addresses the issue of whether superior aminoglycoside derivatives will reach the marketplace in the future. A comparison is made of several key properties of virtually all aminoglycosides that have reached an advanced preclinical development stage, gone into the clinic, or been registered for commercial use over the past 10 years. The following parameters are used for comparisons with already marketed aminoglycosides: antibacterial potency, as measured by relative minimum inhibitory concentrations for 50 percent of the strains tested, against wild-type Pseudomonas aeruginosa; degree of resistance to inactivation by microbial enzymes; and potential for toxicity utilizing comparative acute intravenous lethal doses for 50 percent of the population in mice, values that appear to predict the maximum recommended daily doses in man. An assessment of a number of compounds, including three structurally related to gentamicin, two to sisomicin, two to kanamycin A, three to kanamycin B, and two to fortimicin, revealed that none had overall properties superior to those already being utilized commercially. In no case did a compound prove to be less toxic, and in many instances, the antibacterial potency of the newer agents was lower than that exhibited by the older aminoglycosides. Some increase in resistance to inactivating enzymes was seen, but only BB-K 311 proved refractory to more enzymes than did amikacin. In view of this and the fact that no new agents of promise have moved into the development stage during the past five years, it seems safe to say that the current armamentarium of aminoglycosides is all that will be available for use in the foreseeable future. PMID- 3089003 TI - Resistance surveillance programs and the incidence of gram-negative bacillary resistance to amikacin from 1967 to 1985. AB - Data relating to amikacin resistance among gram-negative bacilli were obtained by means of a review of published literature and resistance surveillance studies. Data from the first several years of amikacin use are difficult to interpret because the 10-micrograms disk used for Kirby-Bauer susceptibility testing resulted in apparent greater resistance than the present 30-micrograms disk. A large United States susceptibility surveillance program that monitors antibiotic use has shown a trend since 1977 of greater susceptibility of Serratia species and greater resistance among Pseudomonas aeruginosa for all the aminoglycosides. Pseudomonas resistance to amikacin has shown the smallest increase of any aminoglycoside. Several hospitals (Strong Memorial Hospital, University of Maryland Cancer Center, and Minneapolis Veterans Administration Medical Center) have reported either no significant change or a decrease in resistance to amikacin when it was the most frequently used aminoglycoside. In a large, 14 center, prospective study, high-level use of amikacin resulted in a significant decrease in resistance to gentamicin and tobramycin (p less than 0.01) and a marginal increase (p less than 0.05) in amikacin resistance. Significantly increased amikacin resistance has been reported from two institutions, neither of which used amikacin as the predominant aminoglycoside. Overall, the high-level use of amikacin in large multi-center surveillance programs for as long as five years has not resulted in a significant increase in amikacin resistance rates at any of the individual institutions surveyed. PMID- 3089004 TI - Cost-effective aminoglycoside therapy in surgical patients. AB - There is a risk that the current pressures for hospital cost containment may result in inappropriately restrictive administrative measures. A failure to take into account all factors in estimating the cost of antibiotic therapy yields a greatly distorted view of the importance of acquisition costs. Higher-priced drugs may actually be more cost-effective if they have greater efficacy, wider therapeutic range, and/or are less costly to prepare and administer. Simple microcomputer modeling techniques may be easily employed to examine the economic consequences of therapeutic decisions. PMID- 3089005 TI - Review of epidemic aminoglycoside resistance worldwide. AB - Epidemic aminoglycoside resistance may be caused by the spread of a species with distinctive chromosomal genes (e.g., Pseudomonas aeruginosa), or it may be due to the dissemination of plasmids or transposons between genera. Although strains of P. aeruginosa resistant to aminoglycosides because of impermeability may cause nosocomial outbreaks, most of the acute increases in aminoglycoside resistance are due to the spread of inactivating enzymes by plasmids. The index species for intergeneric outbreaks is usually Klebsiella pneumoniae carrying the ANT(2") or AAC(3) gene; however, the distribution of resistance varies greatly by location and species. The AAC(6')-I gene is most common in Serratia marcescens and in East Asian isolates of other species, whereas the AAC(3) gene is common in Chile. In the United States, the ANT(2") and AAC(3) genes are particularly common among Enterobacteriaceae, except for Proteus and Providencia, which often carry the AAC(2') gene. The most common patterns of epidemic resistance lead to the inactivation of gentamicin and, less frequently, tobramycin, but only rarely affect amikacin. PMID- 3089008 TI - The American physician: from legacy to legend? PMID- 3089006 TI - Control of emergence of multi-resistant gram-negative bacilli by exclusive use of amikacin. AB - Results of a three-year prospective study of amikacin as the only aminoglycoside used at the Instituto Nacional de la Nutricion "Salvador Zubiran" are presented. During the initial three-month baseline period, resistance to amikacin, gentamicin, and tobramycin among 870 gram-negative bacterial isolates was 3.2 percent, 17.4 percent, and 11.2 percent, respectively. In this period, the overall consumption of aminoglycosides was 69 percent for gentamicin, 30.5 percent for amikacin, and 0.5 percent for tobramycin. In the following period of exclusive amikacin use, sensitivity patterns of 9,344 gram-negative strains isolated over three years were recorded. During this period, amikacin constituted 99.3 percent of all aminoglycosides used. The percentage of gentamicin-resistant gram-negative strains declined to 7.4 percent (p less than 0.0001), whereas the percentage of amikacin-resistant strains did not change significantly. Quarterly trend analysis of aminoglycoside-resistant strains also demonstrated a significant decrease in gentamicin resistance (p less than 0.005) and an overall steady state of amikacin resistance. It is concluded that the exclusive use of amikacin was not accompanied by a significant increase in amikacin resistance during a three-year period, and may even lead to a decrease in resistance to gentamicin and tobramycin among most gram-negative organisms. PMID- 3089007 TI - Surveillance of aminoglycoside resistance. European data. AB - The susceptibility patterns of gram-negative aerobic organisms to aminoglycosides differ widely from one European health care center to another and depend upon local antibiotic prescribing policies. Reports of the susceptibility of Pseudomonas aeruginosa to gentamicin and tobramycin have ranged from as low as 49.8 percent and 77.7 percent, respectively, in Greece, to as high as 96.6 percent and 99.2 percent, respectively, in the United Kingdom. The susceptibility of P. aeruginosa to gentamicin, tobramycin, and amikacin decreased in our hospital from 73.1 percent, 94.8 percent, and 95.6 percent, respectively, in 1982, to 43.1 percent, 70.6 percent, and 74.3 percent, respectively, in 1984. A prospective surveillance study of the susceptibility of gram-negative aerobic bacilli to four aminoglycosides (gentamicin, tobramycin, amikacin, and netilmicin) was performed over a period of 17 months. Gentamicin and tobramycin were freely used, while the use of amikacin was restricted throughout the hospital during a four-month baseline period (May through August 1984). Gentamicin and tobramycin accounted for 94 percent of the aminoglycoside use. During the following 13 months (September 1984 through September 1985), amikacin was used as the first-line aminoglycoside and accounted for more than 97 percent of the aminoglycoside usage. A total of 1,866 organisms were analyzed during the baseline period; 5,429 were analyzed during the amikacin-usage period. The overall susceptibility to gentamicin, tobramycin, amikacin, and netilmicin increased from 86.9 percent, 90.4 percent, 94.2 percent, and 88.3 percent, respectively, to 92.3 percent, 94.0 percent, 97.3 percent, and 92.3 percent, respectively. P. aeruginosa isolates had the most striking changes, with the susceptibility to gentamicin, tobramycin, amikacin, and netilmicin increasing from 43.1 percent, 70.6 percent, 74.3 percent, and 50.6 percent, respectively, during the baseline period, to 64.5 percent, 81.6 percent, 90.8 percent, and 65.1 percent, respectively, during the amikacin-usage period. The use of amikacin as a first-line aminoglycoside, while use of the other aminoglycosides was restricted, seemed to have a favorable influence on the susceptibility pattern of gram negative aerobic isolates in our hospital. PMID- 3089009 TI - Fatal bacterial endocarditis as a complication of permanent indwelling catheters. Report of two cases. AB - Two cases of endocarditis secondary to permanent indwelling catheters are described. In both cases, the catheters were used for parenteral nutrition and became infected with Staphylococci. Secondary endocarditis developed on the tricuspid and aortic valves. Despite removal of the catheters and appropriate antibiotics, both patients died. PMID- 3089010 TI - Hypoproteinemic alkalosis. AB - Hypoproteinemia by itself causes a nonrespiratory ("metabolic") alkalosis. On the average, a decrease in plasma albumin concentration of 1 g/dl produces an increase in "standard" bicarbonate of 3.4 mM/liter, and an apparent base excess of +3.7 meq/liter; it also reduces the value of the normal anion gap by about 3 meq/liter. Concentration of plasma protein should be measured as part of the analysis of acid-base status. Interpretation of acid-base data requires special consideration in "primary hypoproteinemic alkalosis." PMID- 3089011 TI - Drug therapy in the management of acute renal failure. AB - Pharmacologic intervention aimed at altering the natural history of acute renal failure is a routine practice without scientific support of efficacy. Oliguria has become a separate disease entity with an apparent disregard for the underlying condition that caused it. Volume expansion is clearly beneficial in preventing many volume depleted patients from progressing to acute renal failure. While mannitol and furosemide have been used to "convert" oliguric acute renal failure to the more easy to manage non-oliguric acute renal failure, published reports suggest that responders were not as ill as non-responders. The use of dopamine to increase urine flow in patients with established acute renal failure is the current fashion, but there is little evidence that this drug raises the glomerular filtration rate or shortens the course of acute renal failure. These pharmacologic therapies increase the complexity and cost of care with little tangible evidence of benefit to the patient or the physician caring for the patient. PMID- 3089013 TI - Additional eye findings in a girl with the velo-cardio-facial syndrome. PMID- 3089012 TI - Enhanced gallbladder absorption during gallstone formation: the roles of cholesterol saturated bile and gallbladder stasis. AB - Cholesterol saturated bile and gallbladder stasis are important factors in the pathogenesis of cholesterol gallstones. The degree to which either or both of these factors affect gallbladder transport of fluid remains obscure. The authors tested the hypothesis that both cholesterol saturated bile and gallbladder stasis, and not stasis alone, promotes gallbladder fluid absorption. Prairie dogs were maintained for 2 weeks on either a control chow, total parenteral nutrition (TPN), or a 1.2% cholesterol enriched chow. The bile acid pool was labeled with 14C-cholic acid and indexes for cholesterol saturation (CSI) and gallbladder stasis (Rsa) were determined. Fluid transport was indirectly measured by calculating the ratio of gallbladder to hepatic bile concentrations of individual and total biliary lipids. Despite evidence of stasis in prairie dogs maintained on TPN, bile was unsaturated, and gallbladder absorption was not appreciably changed. In contrast, cholesterol-fed animals had cholesterol supersaturated bile, gallbladder stasis, and altered gallbladder absorption, as manifested by a significant change in the ratio of gallbladder to hepatic bile concentrations of individual and total biliary lipids. These data suggest that both cholesterol saturated bile and gallbladder stasis, and not stasis alone, are essential in promoting the enhanced gallbladder absorption, which has previously been observed during early cholesterol gallstone formation. PMID- 3089014 TI - Dietary fatty acids and platelet thromboxane production in puerperal women and their offspring. AB - The effects of the ratio of polyunsaturated to saturated fatty acids in the diet of puerperal women on maternal and neonatal fatty acids and thromboxane A2 synthesis were studied in 91 mother-infant pairs on the fourth to fifth day after delivery. The mothers received a diet with either a low (0.1) or a high (1.5) polyunsaturated to saturated fatty acid ratio for 4 to 5 days. The fatty acid composition in maternal and neonatal serum and in breast milk was determined in 34 mother-infant pairs from both dietary groups. The capacity of the platelets to produce thromboxane B2, a stable metabolite of thromboxane A2, was determined in another 57 mother-infant pairs. The percentage of linoleic acid was increased in maternal and neonatal sera as well as in the breast milk in the group with a high dietary polyunsaturated to saturated fatty acid ratio, whereas the content of arachidonic acid was increased only in maternal serum. This was accompanied by increased platelet thromboxane B2 production in the mothers, and maternal and neonatal thromboxane B2 synthesis correlated significantly with each other (r = 0.43, p less than 0.05). This finding may provide therapeutic possibilities in the future. PMID- 3089016 TI - Fetal acid-base balance in low-risk patients in labor. AB - The fetal acid-base balance from scalp blood in the early and late first stage of labor and from cord arterial blood was assessed in 120 low-risk patients only monitored electronically for 15 minutes at admission. The mean scalp blood pH values were 7.332 at a cervical dilatation of 5 cm and 7.335 at 10 cm cervical dilatation. A low pH value (less than 7.25) was found in 14 patients; five (4.2%) of them had fetal distress. Stethoscopic auscultation failed to identify these cases. Another nine patients had transient abnormal acid-base balance (a check value within 30 minutes was normal), and the fetal heart rate trace (obtained immediately after the sampling) showed no ominous changes in these cases. It is concluded that an abnormal fetal acid-base balance is not uncommon in a low-risk population in labor. However, a critical evaluation of the acid-base balance is necessary, since in most cases the abnormal acid-base balance is transient and of a respiratory, innocuous type without concomitant fetal distress. PMID- 3089015 TI - Pregnancy events and brain damage. AB - A national standard of perinatal care has been established for the early detection and appropriate management of the fetus-neonate who is at risk for distress, brain damage, or death. While perinatal and infant mortality has significantly decreased during the past 10 years, a similar reduction in conditions of severe handicap has not been observed. Undetected antenatal umbilical cord compression is suggested as a possible cause of unexplained brain damage. Basic animal experimentation and clinical experience is reviewed to support the hypothesis. PMID- 3089017 TI - Dynamic proptosis. AB - Dynamic proptosis can be defined as exophthalmos occurring when a variable force is applied to the orbital contents. In a series of 26 patients (13 males and 13 females, 1 to 82 years old), the causes of dynamic proptosis included neurofibromatosis (nine cases), fistulas (three cases), malignancies (three cases), meningoencephaloceles (two cases), mucoceles (two cases), surgery (two cases), orbital varix (two cases), dermoid cysts (two cases), and aneurysm (one case). Dynamic proptosis can be either spontaneous or induced, and can occur either with an intact or an incompetent bony orbit. PMID- 3089018 TI - The participation of macrophages, glomerular procoagulant activity, and factor VIII in glomerular fibrin deposition. Studies on anti-GBM antibody-induced glomerulonephritis in rabbits. AB - The temporal relationships of macrophage accumulation, glomerular fibrin deposition, the expression of glomerular procoagulant activity (PCA), and Factor VIII antigen deposition were studied in rabbits in which antiglomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) developed. The initiation of injury coincided with the accumulation of glomerular macrophages. Glomerular fibrin, assessed by immunofluorescence and by deposition of 125I fibrinogen, paralleled the development of glomerular crescents and renal impairment. Macrophage ingress clearly preceded the deposition of 125I-fibrinogen within glomeruli. Augmented levels of PCA were present in glomeruli prior to the initiation of fibrin deposition, and peak levels coincided with the peak glomerular macrophage presence. Factor VIII related antigen was apparent late in the disease and was present mainly at the margins of fibrinous crescents. These data demonstrate that accumulation of glomerular macrophages precedes glomerular fibrin deposition in anti-GBM GN. The augmentation of PCA, coincident with the appearance of glomerular macrophages, suggests a role for macrophage PCA in the initiation of fibrin deposition within the glomerular tuft in this model. PMID- 3089019 TI - Evolution of the schistosomal hepatic lesions in mice after curative chemotherapy. AB - Mice with 64-day-old Schistosoma mansoni infection (+/- 27 worms, 8-12 pairs) were treated simultaneously with oxamniquine and hycanthone. The cure rate was 100%, and changes occurring thereafter in the liver were sequentially followed by means of histologic, ultrastructural, and immunofluorescence methods. Soon after treatment, hepatitic changes cleared up and periovular granulomas diminished in size. The predominant Type III collagen in granulomas was reduced, and the Type I showed no apparent increase, whereas Type IV did not seem to participate in the process. Collagen fibrils in periovular granulomas changed in texture from dense and more oriented to loose and disorganized. Fibroblasts, at first with marked signs of hyperfunction, became less so at a time when collagen fragments appeared within secondary lysosomes in macrophages and fibroblasts. Schistosomal ovular antigens remained sequestered inside the fibrotic granulomas up to the final, 39th day after treatment. Thus, specific treatment of schistosomiasis showed a beneficial effect upon the hepatic lesions from the very beginning and promoted changes in the periovular granulomas that indicated a rapid, although incomplete, resorption of fibrosis. PMID- 3089020 TI - Characterization of plasma cell populations at autopsy after human allogeneic bone marrow transplantation. AB - Postmortem fixed tissue sections of the lymphoid and digestive systems of eight consecutive leukemic patients dying of various diseases after bone marrow transplantation (BMT) were analyzed for the presence of the heavy chains gamma, alpha, mu, delta, and epsilon and light chains kappa and lambda, with the use of a standard immunoperoxidase method. Two distinct types of plasma cell populations were found. The first type was a widely distributed polyclonal plasma cell population, lacking IgD-positive plasma cells and germinal centers. The second type of plasma cell population, found in 6 of 8 patients, was a group of monoclonal plasma cell populations positive for the heavy chains gamma, alpha, mu, or delta. Recent immunohistologic observations of the human lymph node suggest that the first type of polyclonal plasma cell population could arise from a nonspecific expansion of sIgM+, sIgD- B lymphocytes. The lack of germinal centers, a structure closely involved in specific-antibody production, may correlate with the poor specific-antibody response documented in patients after BMT. The monoclonal plasma cell populations, found with an unexpectedly high frequency, are probably related to a functional T-cell defect. PMID- 3089022 TI - Comment on the evolution of claw-like nails in callitrichids (marmosets/tamarins). AB - A recently proposed scenario for the evolution of a unified complex of exudativory, vertical clinging, and claw-like nails in callitrichids is examined. Consideration of behaviors and morphologies exhibited by Callimico goeldii leads to a decoupling of this "complex," with the early occurrence of claws and vertical clinging in the callitrichid lineage and only later, in some descendents, the development of exudativory and possible related behaviors. PMID- 3089021 TI - Characterization of renal amyloid derived from the variable region of the lambda light chain subgroup II. AB - Amyloid fibrils were extracted from the kidney of a patient (CHE) shown to have tetramers and dimers of a monoclonal lambda light chain in his serum, and whose bone marrow cells in short-term culture synthesized these forms and a smaller lambda fragment of approximately 10,000 to 12,000 daltons. Biochemical and serologic analysis of a fraction of a size (obtained from amyloid fibrils extracted from the kidney) similar to that synthesized by the bone marrow cells revealed a light chain fragment corresponding to the amino terminal end of the variable region of the lambda light chain subgroup II. The presence of similarly sized short fragments of lambda light chain in both the synthesized and deposited protein suggests that aberrant synthesis and/or proteolytic degradation may play a pathogenetic role in the process of amyloidogenesis. PMID- 3089023 TI - Sex determination of prehistoric central California skeletal remains using discriminant analysis of the femur and humerus. AB - A large sample (n = 370) of Central California prehistoric skeletal remains was analyzed for sexual dimorphism of long bones using nine femoral and nine humeral dimensions. Sex of all individuals was assessed using traits of the os pubis. Discriminant analysis was done separately for the robust Early Horizon sample and the Middle/Late Horizon sample. Use of multiple variables did not produce appreciably better results over the use of several of the best variables, analyzed singly. Attention is focused on measurements of maximum diameter femoral head, femoral bicondylar width, and diameter of the humeral head (transverse or vertical). These variables produce excellent separation of the sexes with about 90% accuracy for the Middle/Late Horizon sample. They have been overlooked in the recent literature in which the relative values of length versus midshaft dimensions are debated. The measurements found to be superior in this study are taken at the ends of the bones where durability of these regions is indicated by large sample sizes found in this study. We suggest workers redirect their focus from the midshaft to the ends of the long bones. The discriminant analyses presented here have greater accuracy than most claims for either long bone or cranial sex determination. These standards, based on two samples with differing robusticity, may have applicability for workers in other areas who lack large skeletal samples. PMID- 3089024 TI - Subfossil platyrrhine tibia (primates: Callitrichidae) from Hispaniola: a possible further example of island gigantism. AB - A distal right tibia described by G.S. Miller in 1929 (Smithsonian Misc. Coll. 82[5]:1-16) on the island of Hispaniola is shown to be that of a heretofore unknown extinct platyrrhine and is informally referred to as Ceboid M. Its affinities appear to be with the dwarfed callitrichids, especially Saguinus. It is suggested that Ceboid M represents yet another case of gigantism in the Antilles, in response to a lack of both competitors and predators. A reconsideration of the affinities of Xenothrix mcgregori from Jamaica is suggested. PMID- 3089025 TI - Genetic characterization of Gainj- and Kalam-speaking peoples of Papua New Guinea. AB - The research presented focuses on genetic variation in the Gainj- and Kalam speaking peoples of highland Papua New Guinea. The primary data are typings at 51 genetic loci observed on 600 individuals who reside in 21 census units, called parishes. These data are augmented by cultural and demographic information that has also been collected. Parish sizes are small, ranging from 20 to about 200 individuals. Direct Western contact with these people has been occurring only for the past three decades. Although Westernization is currently increasing, we find that much of the traditional settlement pattern and mate exchange system is preserved. There are segregating variants at 27 loci. Four rare variants are initially described: NP 4-Kalam, ADA 6-Kalam, PEPA 3-Kalam, and FUM 2-Kalam. We find evidence for a new Gm haplotype, a;-, that is recessive to all other Gm haplotypes. It occurs at a high enough frequency, f(a;-) = 0.119, to be considered a "private polymorphism." Average per locus heterozygosity is estimated to be 0.053. This value is not statistically different from levels observed on two modern urban populations. Thus, there is no evidence for a reduced level of genetic variation in these people, despite small parish sizes and a relatively unacculturated social structure. PMID- 3089026 TI - Platelet-activating factor and the kidney. AB - Platelet-activating factor (PAF) represents a group of phospholipids with the basic structure of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine. A number of different cells are capable of producing PAF in response to various stimuli. The initial step of PAF formation is activation of phospholipase A2 in a calcium dependent manner, yielding lyso-PAF. During this step arachidonic acid is also released and can be converted to its respective cyclooxygenase and lipoxygenase products. The lyso-PAF generated is then acetylated in position 2 of the glycerol backbone by a coenzyme A (CoA)-dependent acetyltransferase. An additional pathway may exist whereby PAF is generated de novo from 1-alkyl-2-acetyl-sn-glycerol by phosphocholine transferase. PAF inactivation in cells and blood is by specific acetylhydrolases. PAF exhibits a variety of biological activities including platelet and leukocyte aggregation and activation, increased vascular permeability, respiratory distress, decreased cardiac output, and hypotension. In the kidney PAF can produce decreases in blood flow, glomerular filtration, and fluid and electrolyte excretion. Intrarenal artery injection of PAF may also result in glomerular accumulation of platelets and leukocytes and mild proteinuria. PAF increases prostaglandin formation in the isolated kidney and in cultured glomerular mesangial cells. PAF also causes contraction of mesangial cells. Upon stimulation with calcium ionophore the isolated kidney, isolated glomeruli and medullary cells, and cultured mesangial cells are capable of producing PAF. The potential role for PAF in renal physiology and pathophysiology requires further investigation that may be complicated by 1) the multiple interactions of PAF, prostaglandins, and leukotrienes and 2) the autocoid nature of PAF, which may restrict its action to its site of generation. PMID- 3089027 TI - Effect of amino acid intake on brush-border membrane uptake of sulfur amino acids. AB - Alterations in the intake of sulfur amino acids (SAA) changes the rat renal brush border membrane uptake of the beta-amino acid, taurine. A low-SAA diet enhances and a high-taurine diet reduces uptake (Chesney et al., Kidney Int. 24: 588-594, 1983). Neither the low-SAA diet nor the high-taurine diet alters the time course or concentration-dependent accumulation of the sulfur amino acids methionine and cystine or of inorganic sulfate. By contrast the uptake of beta-alanine, another beta-amino acid that competes with taurine, is greater in animals on the low-SAA diet. The high-taurine diet does not change beta-alanine uptake. The plasma levels of taurine are altered by dietary change, but not the values for methionine and cystine. This study indicates that renal adaptation is expressed for beta-alanine, a nonsulfur-containing beta-amino acid. By contrast, methionine, cystine, and sulfate, which participate in a variety of synthetic and conjugative processes, are not conserved by the renal brush-border surface following ingestion of either a low-methionine and -cystine diet or high-taurine diet. PMID- 3089028 TI - Stimulation of chloride transport by HCO3-CO2 in rabbit cortical collecting tubule. AB - We examined both the role of HCO3-CO2 in Cl transport as well as the effect of in vivo acid-base status on Cl transport by the rabbit cortical collecting tubule. The lumen-to-bath 36Cl tracer flux, expressed as the rate coefficient KCl, was measured in either HEPES-buffered (CO2-free) or HCO3-CO2-containing solutions. Amiloride was added to the perfusate to minimize the transepithelial voltage and thus the electrical driving force for Cl diffusion. Because KCl fell spontaneously with time in HCO3-CO2 solutions in the absence but not the presence of cAMP, we used cAMP throughout to avoid time-dependent changes. Acute in vitro removal of bath HCO3-CO2 reduced KCl. Acetazolamide addition in HEPES-buffered solutions also lowered KCl; KCl could be restored to control values by adding exogenous HCO3-CO2 in the presence of acetazolamide. In vivo acid-base effects on Cl transport were determined by dissecting tubules from either NaHCO3-loaded or NH4Cl-loaded rabbits. Tubules from HCO3-loaded rabbits had higher rates of Cl self exchange. Acute in vitro addition of bath HCO3-CO2 increased KCl and did so to a greater degree in tubules from HCO3-loaded rabbits. Most of this effect of HCO3-CO2 addition on KCl could not be accounted for by Cl-HCO3 exchange; rather, it appeared due to stimulation of Cl self exchange. The data are consistent with 36Cl transport occurring via Cl-HCO3 exchange as well as Cl self exchange. Both processes are acutely stimulated by HCO3 and/or Co2, and both are chronically regulated by in vivo acid-base status. PMID- 3089029 TI - Pulse-wave model of brachial arterial pressure modulation in aging and hypertension. AB - We apply a pulse-wave theory to a model of the human arm arterial system that predicts the changes in the arterial pressure waveform as it traverses the vasculature (increased pulse pressure, sharper main wave, disappearance of the aortic incisura, and appearance of a diastolic dicrotic wave) and also predicts the observed modulation of the waveform during phenylephrine-induced vasoconstriction and nitroglycerin-induced vasodilation. The model considers the arm arterial system as a tapered, distensible tube that bifurcates and then ends in a loop, with sidebranch networks represented by distributed Windkessels. The model uses verifiable values for realistic parameters. We found that the vertical modulation of the dicrotic wave, in humans, decreased with advancing age and with high blood pressure. The model explained these findings in terms of increasing vascular rigidity and decreasing small vessel vasodilator responsiveness. We noted a significant negative correlation between the arterial level of plasma norepinephrine and the amount of modulation of the dicrotic wave after nitroglycerin among subjects 40 yr old or younger, suggesting a sympathetic neurogenic contribution to the vascular abnormalities observed in relatively young patients with essential hypertension. PMID- 3089030 TI - Contribution of prostaglandins to reperfusion-induced ventricular failure in isolated rat hearts. AB - This study was carried out to investigate the possible contribution of endogenous prostaglandin (PG) production to failure of contractile recovery following reperfusion of hypoperfused isolated rat hearts. A 90% reduction in coronary flow rate for 60 min resulted in a time-dependent depression of contractile force and an elevation in resting tension. Reperfusion produced a slight (approximately 11%) recovery of contractile force, whereas resting tension remained elevated. Reperfusion was a potent stimulus for PG (as assessed by 6 keto-PGF1 alpha) release and resulted in levels that were significantly higher than those observed prior to ischemia. When PG synthesis was inhibited by the nonsteroidal anti inflammatory drugs ibuprofen, indomethacin, or acetylsalicylic acid (ASA), recovery of ventricular contractility on reperfusion was significantly higher than that seen in the absence of drugs. Ibuprofen was the most effective, producing an average recovery of 70% (P less than 0.05 from control). Indomethacin and ASA produced approximately a 40% (P less than 0.05) and 35% (P less than 0.05) recovery of contractile force, respectively. The improved recovery in contractility was significantly depressed by the addition of low concentrations of prostacyclin (PGI2) and PGF2 alpha, whereas PGE2 and 6 keto PGF1 alpha, the hydrolysis product of PGI2, were ineffective. The effects on resting tension were inconsistent. PG release during reperfusion was unrelated either to the length of the initial period of reduced coronary flow or the degree of contractile recovery; it was attenuated either by a reduction in or by an elevation of Ca concentration. These results indicate that endogenous PGs mediate, at least in part, reperfusion-associated failure of ventricular function. PMID- 3089031 TI - Sympathomimetic pressor responses to thyrotropin-releasing hormone in rats. AB - Cardiovascular responses to centrally administered thyrotropin-releasing hormone (TRH) were studied in urethan-anesthetized rats to allow continuous recording of attendant changes in sympathetic nerve activity. Intracerebroventricular infusions of TRH (0.05-5.0 micrograms) consistently increased not only blood pressure and heart rate, but also spike frequency in splanchnic, renal, or cervical sympathetic nerves. Parasympathetic inhibition seemed unlikely because TRH responses were unaltered by cholinergic blockade with atropine, and efferent vagal nerve firing, instead of being reduced, was actually increased by TRH. An increased secretion of endogenous vasopressin also appeared unlikely, since TRH responses were essentially unaffected by either hypophysectomy or pretreatment with a vasopressin antagonist. Inasmuch as pharmacological ganglion blockade with pentolinium eliminated increases in splanchnic nerve firing but reduced the attendant tachycardia by only 50%, residual tachycardia after ganglion blockade was considered partly due to persistent sympathetic cardioaccelerator tone. On the other hand, because pressor responses to TRH were always accompanied by increased sympathetic nerve firing and were completely abolished after pentolinium-induced ganglioplegia, they were attributed solely to sympathetic hyperactivity. PMID- 3089032 TI - Accumulation of polymorphonuclear leukocytes during 3-h experimental myocardial ischemia. AB - Recent evidence indicates that mechanical obstruction of capillaries by leukocytes plays an important role in the "no-reflow" phenomenon in the heart. This entrapment of leukocytes in the microcirculation precedes their recognized role in an inflammatory reaction following ischemia. It is a fundamental rheological mechanism that may be associated with ischemic injury and reflow injury and it has not been elucidated. To explore the accumulation of granulocytes during myocardial ischemia we studied the accumulation of 111Inlabeled autologous granulocytes in acutely ischemic myocardium during 3 h of flow reduction with and without a subsequent period of reflow in open-chest dogs. Granulocytes accumulated in the ischemic endocardium of all animals and, for the majority of dogs, also in the epicardium. Accumulation in the endocardium was enhanced by reperfusion. The entrapped leukocytes may have an influence on the increase in resistance, since regional accumulation of leukocytes in the endocardium inversely correlated with ischemic blood flow during 3 h of ischemia. The tissue water content measured from the wet and dry weights of biopsies showed a significant positive correlation with the number of entrapped granulocytes. These results suggest that collateral flow is an important mechanism of leukocyte arrival early in ischemic myocardium and that reperfusion enhances granulocyte accumulation. PMID- 3089033 TI - Lithium potentiation of tricyclic antidepressants following lack of T3 potentiation. AB - Four patients whose depressions were failing to respond to administration of tricyclic antidepressants were given separate trials of T3 and lithium. In all four cases, T3 failed to potentiate the antidepressant, whereas the lithium did. PMID- 3089034 TI - Patterns of Schistosoma haematobium egg distribution in the human lower urinary tract. I. Noncancerous lower urinary tracts. AB - Schistosoma haematobium egg burdens (eggs/g of tissue) of 17 anatomic segments of lower urinary tracts from 32 unselected Egyptian autopsies have been determined by tissue digestion and replicate counts of aliquots of the digestate. There were three anatomic patterns of egg distribution in these lower urinary tracts: apical, basal and diffuse. Regression of egg burdens of each of the anatomic segments as the dependent variable against egg burdens of the entire lower urinary burden yielded a good fit for 15 of 17 of these segments. Statistical analyses revealed that many of these equations for discrete anatomic segments can be combined, generally giving one equation for anatomic regions which are in continuity, indicating that the female worm lives and oviposits in specified venous plexes. These equations also suggest that there are differences in the rates, duration and onset of egg accumulation which may be responsible for schistosomal obstructive uropathy as a cause of death in fairly young individuals. PMID- 3089035 TI - Patterns of Schistosoma haematobium egg distribution in the human lower urinary tract. III. Cancerous lower urinary tracts. AB - The distribution of S. haematobium eggs in urinary bladders containing tumors and removed at surgery has been studied; the majority of these tumors are well differentiated squamous cell carcinomas. The same three anatomic patterns of egg accumulation described in part I of this series (noncancerous lower urinary tracts) were found in these cancerous bladders, but, in addition, most of the tumors were surrounded by a collar of heavy S. haematobium egg deposition. The egg burdens in these collars were, on the average, twice the average egg burden in the remainder of the urinary bladder. These collars do not seem to be artifacts created by growth of the tumor and subsequent displacement of the adjacent normal tissue, creating a region of heavy egg concentrations; rather, these heavy S. haematobium egg concentrations seem to act as promoters of urothelial carcinogenesis. PMID- 3089036 TI - Morbidity from urinary schistosomiasis in relation to intensity of infection in the Natal Province of South Africa. AB - Morbidity from urinary schistosomiasis was assessed on clinical, radiological, parasitologic and biochemical evidence in 510 schoolchildren living in a Schistosoma haematobium endemic area. The results were viewed against the background of the prevalence and intensity of infection in the subjects. Clinical morbidity correlated well with the intensity of infection, the latter in turn being influenced by factors such as water contact pattern, sex and water source. A surprisingly high prevalence (42%) of abnormalities was observed in the urinary tract of subjects, but no relationship could be demonstrated between the intensity of infection and structural damage to the urinary tract. Urographic changes were more severe in the 11-15 year age group than in the 6-10 year group. Significant rectal involvement (76%) in S. haematobium-infected subjects was regarded as a reflection of the heavy worm burdens borne by these children. The morbidity described in this study indicates a definite degree of pathology in the infected children but the impression was that they suffered only mild disability. However, given the structural lesions seen on urography and the limited sensitivity of the biochemical tests used for the assessment of renal function, renal pathology cannot be ruled out. Further studies on the renal status of these subjects are essential. PMID- 3089037 TI - Isolation and characterization of Schistosoma haematobium egg antigens. AB - Schistosoma haematobium soluble egg antigen (ShSEA) was prepared from eggs isolated from the livers of hamsters or mice infected for at least 3 months. Immunoaffinity purified S. haematobium egg antigens (ShSh) were isolated by first passing ShSEA through a column containing anti-S. mansoni hamster IgG coupled to CNBr-activated Sepharose 4B, and recycling the unbound fraction until no more bound material could be eluted with an acid wash. The unbound fraction was then filtered through a second antibody affinity column containing anti-S. haematobium hamster IgG, and in the acid eluate the ShSh antigens were obtained. This antigenic preparation was shown by PAGE to contain at least 6 distinct bands ranging in molecular weight (Mr) from 116 to less than 31 Kd. A 40 Kd polypeptide was identified by both silver staining and EITB as specific for S. haematobium eggs. In addition, a 55 Kd worm-egg shared antigen was identified as a prominent band in EITB expressed during a primary S. haematobium hamster infection. The sera from hamsters harboring patent S. haematobium or S. mansoni infections were reacted by ELISA with ShSh antigens. The anti-Sh sera showed significantly higher absorbance values than the anti-Sm sera, demonstrating that only a minor population of S. mansoni cross-reactive egg antigens is still present in the ShSh antigens. Sera collected weekly for 13 weeks from hamsters with a primary infection of S. haematobium were then tested by ELISA against ShSh, ShSEA and SmSEA antigens. Antibody levels against both ShSEA and SmSEA were shown to increase early in infection (2 weeks). Moreover, antibody levels to ShSh did not increase until week 5 post-infection. These findings suggest that the purification procedure utilized results in the elimination of most of the S. mansoni worm antigens cross-reactive with S. haematobium eggs. The ShSh antigens had shown a high degree of sensitivity and stage-species specificity also suggesting their potential as antigens for the immunodiagnosis of schistosomiasis haematobia. PMID- 3089038 TI - Discrepancies in outcome of a control program for schistosomiasis haematobia in Fayoum governorate, Egypt. AB - A large scale mollusciciding and chemotherapy program in the Fayoum area of Egypt was reported to have decreased prevalence of schistosomiasis haematobia from 46% to 7% in approximately 12 years. In order to assess the uniformity of results reported, we have studied the prevalence and intensity of urinary tract disease in a random sample of children aged 6 months-12 years in 3 areas selected on the basis of distance from the main canal supplying Fayoum and where mollusciciding was applied. Only 1 location near the main canal showed low prevalence (2.2%), while in the other 2 areas prevalence was 75.3% and 61.3%. Intensity of infection and disease were significantly more in the latter 2 locations. Following chemotherapy, a marked reduction in prevalence and intensity of infection and reversal of pathology was seen. Since the reported favorable results of the Fayoum project were used to implement a wider control program in southern Egypt, an independent assessment must be included in future plans. PMID- 3089039 TI - Testicular schistosomiasis mansoni: a differential diagnostic problem with testicular neoplasias. AB - We report a case of testicular schistosomiasis mansoni that was surgically treated as a tumor. Massive enlargement of the testicle (twice the original volume) was due to an extensive granulomatous reaction. PMID- 3089040 TI - Immune responses during human schistosomiasis. XII. Differential responsiveness in patients with hepatosplenic disease. AB - Thirty-four hospitalized patients and 12 ambulatory patients, all with hepatosplenic schistosomiasis mansoni were evaluated in regard to their peripheral blood mononuclear (PBMN) cell responses to schistosomal antigenic preparations and compared with groups of 40 patients with the hepatointestinal form and 39 patients with the more common, chronic intestinal form of schistosomiasis mansoni. PBMN cell blastogenic responses were measured upon exposure to schistosomal egg antigens (SEA), adult worm antigens (SWAP) and a cercarial antigenic preparation (CERC). All groups had some individuals who did not respond to some or all of these preparations. In the hospitalized hepatosplenic group greater than 50% did not respond to SEA. Analysis of the responses in each group revealed that all responders could be subdivided into moderate and high responders. High responders to SEA had experimental minus control values of greater than 8,000 counts per minute (CPM). For SWAP and CERC, this arbitrary cut-off value was greater than 25,000 CPM and greater than 11,000 CPM, respectively. The percent of high SEA responders in the groups differed considerably. This was 23% in the chronic intestinal group, 40% in the chronic hepatointestinal group, 67% for ambulatory hepatosplenic patients and 20% for hospitalized hepatosplenic patients. Previous studies had demonstrated that 94% of patients with early (2-3 month) acute schistosomiasis mansoni were high responders to SEA and none were nonresponders. Furthermore, at the other end of the spectrum, 100% of former schistosomiasis mansoni patients (treated and cured 7-35 years previously) were high responders to SEA. None were nonresponders to any of the antigen preparations. It is proposed that during acute infection all patients express vigorous responses to SEA. Upon continued infection most patients (75%) modulate this florid response. However, continued high responders comprise 40% of the chronic hepatointestinal cases and almost 70% of the ambulatory hepatosplenic patients. These latter 2 groups may likely represent early forms of the severe clinical disease found in the hospitalized hepatosplenic patient population. Fifty percent of the hospitalized group appear anergic and no longer respond to SEA, while only 20% are high responders. Long after chemotherapy it appears that the anti-SEA regulatory mechanisms of former chronic patients have subsided, leaving strong anti-SEA responsiveness. PMID- 3089041 TI - Bone marrow aspirate culture superior to streptokinase clot culture and 8 ml 1:10 blood-to-broth ratio blood culture for diagnosis of typhoid fever. AB - We compared the sensitivities of bone marrow aspirate culture (BMAC), 3 ml 1:4 and 8 ml 1:10 blood-to-broth ratio blood cultures (BC), 8 ml streptokinase clot culture (STKCC) and rectal swab culture (RSC) for isolating Salmonella typhi and S. paratyphi A from 61 patients with typhoid or paratyphoid fever in Jakarta, Indonesia. BMAC (92%) was significantly more sensitive than 8 ml BC (62%), 8 ml STKCC (51%), 3 ml BC (44%), RSC (56%) and the 19 ml combination of all three BC methods (71%). The combination of the three BC methods and RSC had an isolation rate of 87%. In Jakarta the diagnosis of typhoid fever cannot be confidently excluded unless a BMAC is done. PMID- 3089042 TI - The sensitivity of various serologic tests in the diagnosis of Rocky Mountain spotted fever. AB - Sensitivity indices for various serologic tests in the diagnosis of Rocky Mountain spotted fever (RMSF) were determined from RMSF surveillance data collected at the Centers for Disease Control (CDC) during 1981-1984. During these 4 years, a total of 4,141 cases of RMSF in the U.S. were reported to CDC. Case report forms, which include information on dates and results of serologic testing, were received for 3,567 of these cases; 1,774 were laboratory-confirmed according to criteria published previously by CDC. Sensitivity indices for the Weil-Felix (Proteus OX-19, OX-2), indirect fluorescent antibody (IFA), latex agglutination (LA), complement fixation (CF) and indirect hemagglutination (IHA) tests were examined by analyzing cases confirmed by other means, in which data concerning the test in question were available. Analysis of serum pairs for a 4 fold or greater increase in antibody titer or a minimum diagnostic titer indicated high sensitivity indices for IHA (96%) and IFA (94%), but lower sensitivity indices for OX-19 (70%), OX-2 (47%), CF (63%) and LA (71%). IFA and IHA appear to be the most sensitive serologic tests currently in use for the diagnosis of RMSF. PMID- 3089043 TI - The cell-saver and autologous transfusion: an underutilized resource in vascular surgery. AB - The vascular surgeon's best resource for blood transfusion is the patient's own blood. It is readily available for recycling, already precisely typed and crossmatched, and without the risk of transfusion-related diseases such as hepatitis and AIDS. The relative ease, safety, and cost-effectiveness of autologous blood transfusions, intraoperative autotransfusions, and postoperative autotransfusions has been shown in our hospital experience with 320 cases and in the literature. We predict that autologous donor blood and autotransfusion will soon be widely accepted and utilized as the best and safest method of blood replacement. PMID- 3089044 TI - Complications of parenteral nutrition. AB - All hospitalized patients except infants (a total of 1,647 patients) who received central venous TPN solutions at UCDMC from 1981 through 1985 were studied to determine the incidence of complications from the use of TPN. A complication was considered to have occurred if the patient experienced obvious morbidity, mortality, or both; an event known to be deleterious, despite a lack of demonstrable morbidity; or premature loss of the central venous catheter. Complications related to catheter placement occurred in 5.7 percent of patients, sepsis in 6.5 percent, mechanical complications in 9 percent, and metabolic complications in 7.7 percent. The incidence of induction of sepsis increased during 1984 to 1985 due to the introduction of multilumen central venous catheters. The most frequent catheter placement complications were hemorrhage and pneumothorax. Major venous thrombosis and nursing mishaps were the most common mechanical complications. Metabolic complications were infrequent and were generally not severe after adjustment of the protocol in late 1981. Four patients (0.2 percent) died from TPN-associated complications: a child on home TPN who underwent a catheter change and in whom hyperosmolar hyperglycemic coma developed, a patient with end-stage chronic obstructive pulmonary disease in whom tension pneumothorax occurred, a patient who died from complications of subclavian artery laceration, and a patient who died from Candida septicemia. Complications of TPN are frequent and may be severe. Quality assurance mechanisms for identification of these complications are necessary and should form the basis for the establishment of appropriate protocols. PMID- 3089045 TI - Effect of thyrotropin-releasing hormone on vestibular compensation in primates. AB - Continual administration of thyrotropin-releasing hormone (TRH) (250 micrograms/kg/day) for 14 days using an osmotic mini-pump in unilateral labyrinthectomized squirrel monkeys induced accelerated vestibular compensation. Decrease in total gait deviation counts and reduction of slow-phase eye velocity of spontaneous nystagmus were significantly faster in the TRH-treated group as compared with the control group. PMID- 3089046 TI - Is bulimia an affective disorder? PMID- 3089047 TI - [Relation between long-term artificial respiration and respiratory tract infection in 104 patients in a surgical intensive care unit]. AB - The authors studied over a period of two years prospective connections between long-term artificial respiration and infections of the lower respiratory tract. A distinction was made between colonisation (RTC) and infection (RTI). Besides the incidence rate of RTC and RTI the severity of the infection was recorded. The connections between the underlying disease, the duration of artificial respiration, the age of the patient and the antibiotic treatment with the pathogenesis of RTC and RTI were studied. In more than half of the patients RTC could be demonstrated already within the first 24 hours; differences were related to underlying disease, start of ventilation and antibiotic treatment. The RTI incidence rate in all 104 ventilated patients was 67.3%. 19.2% of these already had RTI when respiration was initiated. Thus 48.1% of the patients developed RTI during artificial respiration. The diagnosis RTI was most frequent on the fourth day of respiration, and 80% of all RTI cases had appeared by the fifth day. The highest incidence was seen in patients with a thoracic trauma (85.7%). This group of patients also included the majority of life threatening cases of RTI. In one quarter of the patients who developed RTI during artificial respiration there was no significant deterioration of pulmonary gas exchange; in 56% however, respiration was impaired to a life-threatening extent. The age of the patients did not have any bearing on the incidence rate and severity of RTI; however, all patients under artificial respiration who were over 70 years of age, died if the severity of the RTI had to be classified as life-threatening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089048 TI - Alfentanil supplemented anaesthesia for short procedures. A double-blind study of alfentanil used with etomidate and enflurane for day cases. AB - Thirty-nine unpremedicated patients who presented for cystoscopy were given either alfentanil or saline in a random double-blind fashion immediately before anaesthesia with etomidate, nitrous oxide and enflurane. Alfentanil significantly reduced myoclonus associated with etomidate. During anaesthesia, patients who received alfentanil had smaller minute volumes, lower respiratory frequencies, and smaller increases in heart rate. The incidence of apnoea was not significantly increased. After operation, patients who received alfentanil were prescribed significantly more analgesia, possibly because of their reduced uptake of volatile anaesthetic agent. It is concluded that supplementation with alfentanil improves the quality of anaesthesia induced with etomidate. PMID- 3089049 TI - Comparison of effects of fentanyl and alfentanil on intra-ocular pressure. A double-blind controlled trial. AB - The effects of fentanyl and alfentanil on intra-ocular pressure during anaesthesia were investigated in 50 consecutive patients in a double-blind controlled trial. Both drugs produced a significant reduction in intraocular pressure (p less than 0.01). Alfentanil produced significantly greater reduction (48.5 percent) than fentanyl (28.6 percent) (p less than 0.01). A small but statistically significant reduction in arterial pressure (15 percent approximately) and heart rate (18 percent approximately), were observed with both agents, but no significant differences between them were noted. It is suggested that alfentanil may be a suitable alternative to fentanyl in ophthalmic anaesthesia. PMID- 3089050 TI - Caudal analgesia for perianal surgery. A comparison between bupivacaine and diamorphine. AB - Seventy-three patients undergoing elective perianal surgery were randomly divided into a control group, a group who received a caudal injection of 20 ml bupivacaine 0.5% plain and a group who received diamorphine 2.5 mg in 10 ml normal saline by caudal injection; a comparison was then made of postoperative analgesia requirements. The bupivacaine group had better analgesia than the control group for the first 8 hours, after which there was no difference. The diamorphine group had better analgesia than the control group for the first 24 hours postoperatively. Side effects were less in the diamorphine group than the control, or the bupivacaine group. In particular, 41% of the bupivacaine group complained of some degree of urinary retention and one patient required temporary catheterisation. It is concluded that caudal diamorphine gives good postoperative analgesia for perianal operations, particularly when motor blockade is not wanted by the surgeon. PMID- 3089052 TI - Intravenous anaesthesia with propofol and alfentanil. The influence of age and weight. AB - Sixty healthy patients undergoing body surface surgery were anaesthetised with continuous infusions of propofol (200 micrograms/kg/minute) and alfentanil (0.25 microgram/kg/minute). Additional bolus doses of propofol (20 mg) were given if movement occurred. The incidence of patient movement in response to skin incision was significantly less in patients over 45 years of age than in those below 45 years (p less than 0.05). Maintenance dosage of propofol sufficient to abolish movement decreased with increasing age (p less than 0.001). Systolic blood pressure decreased in most patients over the first 10 minutes of anaesthesia and the magnitude of this decrease increased with age (p less than 0.0001). These parameters did not correlate strongly with body weight. Dose requirements of propofol are not the same for patients of all ages and strongly suggest that young and old patients should not be treated as a homogeneous group, either for investigative or clinical purposes. PMID- 3089051 TI - Propofol and alfentanil infusion. A comparison with methohexitone and alfentanil for major surgery. AB - In 42 patients undergoing major surgery, anaesthesia was induced by intravenous alfentanil 10 micrograms/kg together with methohexitone 1.5 mg/kg or propofol 2 mg/kg. An infusion of six times these doses per hour was then started; the rate was varied subsequently as indicated by the monitoring of arterial blood pressure, heart rate, EEG and frontalis electromyogram. The mean duration of infusion was 76.7 minutes for propofol and 74.5 minutes for methohexitone and the infusion was stopped about 10 minutes before the end of surgery in each group. The induction dose differed, but the total dose requirement for the two drugs was similar. In every case, anaesthesia was satisfactory. Methohexitone caused a significant rise in mean pulse rate throughout anaesthesia (p less than 0.05, paired t-test). There was no change in mean pulse rate during propofol infusion. The dose of alfentanil used provided excellent control of autonomic reflexes, with negligible respiratory depression. Naloxone was not required. Propofol provided better anaesthesia than methohexitone, with fewer side effects (p less than 0.05, Chi squared test), easier control of the level of narcosis and faster recovery (p less than 0.001, t-test after log transformation). PMID- 3089053 TI - Carbon dioxide elimination during apnoea. PMID- 3089054 TI - Transdermal glyceryl trinitrate. PMID- 3089055 TI - Pneumothorax following insertion of a nasogastric tube. PMID- 3089056 TI - Characterization of cyanobacterial ferredoxin-NADP+ oxidoreductase molecular heterogeneity using chromatofocusing. AB - Chromatofocusing has been used as an analytical tool to check preparations of the enzyme ferredoxin-NADP+ oxidoreductase (EC 1.18.1.2) purified in either the presence or absence of the serine protease inhibitor phenylmethylsulfonyl fluoride from the cyanobacterium Anabaena sp. strain 7119. Only one isoelectric species was found when the crude extract was processed in the presence of the protease inhibitor. Nevertheless, when the inhibitor was omitted, four ionic forms of the enzyme--showing apparent pI's in the range 4.3-4.6--were separated after chromatofocusing of the purified preparation. These forms were found to differ in their specific activities, exhibiting, on the other hand, lower values than the single one obtained in the presence of the protease inhibitor. Analysis by acrylamide gel electrophoresis revealed virtually a single main protein band except for the ionic form of pI 4.39, which was clearly resolved into two active components. Except for the more basic form, which seems to be an homodimer of Mr 80,000, all the protein components were found to be monomeric species in the range Mr 33,000-38,000. These results indicate that the molecular heterogeneity of the ferredoxin-NADP+ oxidoreductase purified from the cyanobacterium Anabaena sp. strain 7119 may result from the activity of a protease present in the whole cell homogenates. On the other hand, these data also point out that chromatofocusing should be considered as an effective technique in the isolation and characterization of the different molecular forms of this enzyme. PMID- 3089058 TI - Purification of potato lectin (Solanum tuberosum agglutinin) from tubers or fruits using chromatofocusing. AB - The lectin from potato tubers (Solanum tuberosum agglutinin) has been purified to homogeneity by a procedure involving chromatofocusing followed by gel filtration. By subjecting tuber and fruit extracts from an individual plant to this purification scheme, it was demonstrated that the lectins from those two tissues, though similar, are not identical. PMID- 3089057 TI - The use of galactosyltransferase to probe nitrocellulose-immobilized glycoproteins for nonreducing terminal N-acetylglucosamine residues. AB - We report the use of UDPgalactose:N-acetyl-D-glucosaminyl-glycopeptide 4-beta-D galactosyl-transferase (EC 2.4.1.38), purified from bovine milk, to detect nonreducing terminal N-acetylglucosamine residues on glycoproteins immobilized on nitrocellulose by electrophoretic transfer from sodium dodecyl sulfate polyacrylamide gels. Soluble galactosyltransferase incorporates radiolabeled galactose from the substrate UDP-[6-3H]galactose into the appropriate immobilized acceptor with high specificity. Incorporation is proportional to substrate amount and is saturable with time. The kinetics of labeling are independent of substrate amount. Half-maximal incorporation occurs by 4 h and saturation occurs by 16 h. We have used galactosyltransferase as a probe (i) to verify the presence of nonreducing terminal N-acetylglucosamine residues in bovine rod outer segment membrane rhodopsin and in several glycoproteins in F9 murine teratocarcinoma cells and (ii) to detect previously reported endo-beta-N-acetylglucosaminidase activity in a commercial preparation of endoglycosidase F. PMID- 3089059 TI - Microbiological analysis of 5-formyltetrahydrofolic acid and other folates using an automatic 96-well plate reader. AB - The growth of auxotrophic bacteria remains the method of choice for the determination of biologically active folate metabolites in plasma. This report describes a microbiological assay for folates adapted to use disposable 96-well plates and an automatic plate reader. The modifications in the assay decreased reagent costs and made the analysis of hundreds of samples per day possible with a sensitivity limit of 10 fmol of (6S)-5-formyltetrahydrofolic acid. This limit compares favorably with that of previously reported, more laborious methods. The unnatural 6R diastereomer of 5-formyltetrahydrofolic acid did not interfere with the microbiological assay of the natural 6S diastereomer. PMID- 3089060 TI - Preparation of (6R)-tetrahydrofolic acid and (6R)-5-formyltetrahydrofolic acid of high stereochemical purity. AB - Commercially available 5-formyltetrahydrofolate (5-CHO-H4PteGlu) is chemically prepared in a reaction that introduces an asymmetric center at the 6 carbon, and hence is the mixture of diastereomers differing in chirality about this position. (6R)-5-CHO-H4PteGlu, the diastereomer that is not normally found in vivo, was prepared from folic acid. Folic acid was chemically reduced and (6R) tetrahydrofolate (H4PteGlu) was obtained from the resultant (6R,S)-H4PteGlu by enzymatic consumption of the natural diastereomer of (6R,S)-5,10-CH2-H4PteGlu (reversibly formed from (6R,S)-H4PteGlu in the presence of formaldehyde) with Lactobacillus casei thymidylate synthase. The 5 position of purified (6R) H4PteGlu was directly formylated in a carbodiimide-catalyzed reaction. The level of contamination of these preparations with the corresponding 6S diastereomers was estimated using the binding of fluorodeoxyuridylate to thymidylate synthase promoted by folate cofactor (for H4PteGlu) and by the growth of folate requiring bacteria (for 5-CHO-H4PteGlu). Purified preparations of (6R)-H4PteGlu promoted the binding of fluorodeoxyuridylate to L. casei thymidylate synthase (in the presence of formaldehyde) only at concentrations greater than 1000-fold higher than equiactive levels of (6S)-H4PteGlu. Likewise, the (6R)-5-CHO-H4PteGlu made by this method was 600 times less active as a growth factor for Pediococcus cerevisiae than was authentic (6S)-5-CHO-H4PteGlu. Hence, the minimum stereochemical purity of these preparations was 99.9% for (6R)-H4PteGlu and 99.8% for (6R)-5-CHO-H4PteGlu. PMID- 3089061 TI - A sensitive spectrophotometric method for the determination of superoxide dismutase activity in tissue extracts. AB - Superoxide dismutase (EC 1.15.1.1) has been assayed by a spectrophotometric method based on the inhibition of a superoxide-driven NADH oxidation. The assay consists of a purely chemical reaction sequence which involves EDTA, Mn(II), mercaptoethanol, and molecular oxygen, requiring neither auxiliary enzymes nor sophisticated equipment. The method is very flexible and rapid and is applicable with high sensitivity to the determination of both pure and crude superoxide dismutase preparations. The decrease of the rate of NADH oxidation is a function of enzyme concentration, and saturation levels are attainable. Fifty percent inhibition, corresponding to one unit of the enzyme, is produced by approximately 15 ng of pure superoxide dismutase. Experiments on rat liver cytosol have shown the specificity of the method for superoxide dismutase. Moreover, common cellular components do not interfere with the measurement, except for hemoglobin when present at relatively high concentrations. The assay is performed at physiological pH and is unaffected by catalase. PMID- 3089062 TI - Indirect assays for deoxyhypusine hydroxylase using dual-label ratio changes and oxidative release of radioactivity. AB - Two procedures for rapid assay of deoxyhypusine hydroxylase activity are described. One of these assays measures changes in the 3H:14C ratio of dual labeled protein that results from the release of tritium from a specific position in the side chain of the 3H,14C-labeled constituent amino acid deoxyhypusine upon its conversion to [3H,14C]hypusine. The other assay relies upon release of radioactivity from product protein by periodate oxidation of the radiolabeled side chain of component hypusine. The good correspondence of each of these assays with the ion exchange chromatographic method which measures hypusine and deoxyhypusine in acid hydrolysates of protein indicates that each provides a valid means of determining deoxyhypusine hydroxylase activity. PMID- 3089063 TI - A radioimmune assay of ganglioside GM1 synthase using cholera toxin. AB - A radioimmune assay for uridine 5'-diphosphate-galactose (UDP-Gal):GM2 galactosyltransferase, which synthesizes GM1, has been developed utilizing cholera toxin. This assay is more sensitive and simpler than previously used assays. Radioactive nucleotide substrate and GM2 were incubated with an enzyme sample, and a radiolabeled product, GM1, was reacted with cholera toxin. The GM1 cholera toxin complex was further reacted with anti-cholera toxin and Staphylococcus aureus cell suspension. The resulting complex was transferred onto a nitrocellulose membrane and quantitated by liquid scintillation counting. This assay was found to be sensitive for the detection of 100 pmol of the reaction product, GM1. With this assay method, some properties of the crude enzyme extracts from rat liver were studied. The enzyme had a pH optimum of 6.5-7.0 and required Mn2+. The Km values for UDP-Gal and GM2 were 0.12 mM and 6 microM, respectively. PMID- 3089064 TI - Root-analogue versus crown-analogue dentin: a radioautographic and ultrastructural investigation of the mouse incisor. AB - The present paper reports on differences between the root- and crown-analogue dentin portions of the continuously growing mouse incisor. Conventional light microscopy and radioautography were used to study dentin formation and the uptake of [3H]-proline and [3H]-serine. It was found that, although the dentin apposition rate along the crown-analogue part (covered by enamel) equalled or slightly exceeded that along the root-analogue part (covered by cementum), the processing of predentin into dentin was considerably faster in the root aspect. Comparison of the two dentin portions at the ultrastructural level revealed that differences occurred in the morphology of the secretory granules of the odontoblast layer. Two types of granules were observed: those that were and those that were not loaded with electron-dense particles of 30 nm diameter. While the former type was most frequent along the crown-analogue aspect of the incisor, the latter type was particularly found along its root-analogue aspect. This difference may reflect differences between the two dentin portions in the composition of the noncollagenous matrix. PMID- 3089065 TI - Systemic responses to tourniquet release in children. AB - The hemodynamic and metabolic effects of deflation of pneumatic tourniquets were assessed in 15 children, seven of whom had bilateral tourniquets applied. Systemic acidosis from release of lactate and PaCO2 after tourniquet deflation did not cause adverse effects in these healthy children. Larger increases in lactate were seen with longer tourniquet inflation times (greater than 75 min) or with bilateral tourniquets. The greatest decrease in pH was seen with simultaneous deflation of bilateral tourniquets. Heart rate did not change with tourniquet deflation, whereas systolic blood pressure decreased 8-10 mm Hg with deflation. Blood pressure returned to control values within 5-10 min; no arrhythmias were seen. Recommendations to minimize the systemic metabolic effects after release of tourniquets in children under general anesthesia include the following: 1) attempt to limit tourniquet inflation times to less than 75 min; 2) use controlled ventilation prior to and after tourniquet deflation to remove the respiratory component of acidosis; 3) check blood gas tensions within 5 min of tourniquet deflation in children with long tourniquet inflation times (greater than 75 min), and where bilateral tourniquets are deflated simultaneously or within 30 min of each other. PMID- 3089066 TI - Esophageal intubation: a review of detection techniques. PMID- 3089067 TI - Early warning sign of an accidental endobronchial intubation: a sudden drop or sudden rise in PACO2? PMID- 3089068 TI - Blood gas values change slowly in apneic organ donors. PMID- 3089069 TI - Multidosage medication vials: a study of sterility, use patterns, and cost effectiveness. PMID- 3089070 TI - Necessary side of certification. PMID- 3089071 TI - Scoring system suggested to determine staffing level. PMID- 3089072 TI - Development and results of the third Infection Control Certification examination, Nov. 16, 1985. Test development. PMID- 3089073 TI - Influence of transdermal nitrates on exercise capacity in patients with stable angina. AB - Twenty patients completed a double-blind cross-over study to determine the influence of a transdermal preparation of Nitroglycerin on exercise performance in stable angina. Angiographically proven two or three vessel coronary disease was present in all. After a base-line exercise test the active device was titrated to efficacy or side effects and the number of patches thereafter remained constant (2-6 patches per day; mean 3.5). Patients were randomly allocated to active treatment or placebo, and further exercise tests were performed at 2 hours and 26 hours after application of the device. Patients were then crossed over after one days rest to the opposite treatment group, and exercise studies repeated. Two hours after application of transdermal nitroglycerin total exercise duration increased (mean 14.0 minutes) compared to placebo (12.5 minutes) and control (12.0 minutes) (p less than 0.05). This effect was maintained at 26 hours. Exercise time to anginal threshold (angina + 1.5 mm ST segment depression) was increased at 2 hours and 26 hours with active drug by 11% compared to placebo and by 22% in comparison to control. Double product of heart rate and blood pressure was not significantly different in treated and placebo groups. Oral nitroglycerin consumption assessed during the titration phase was reduced by 71%. It is concluded that transdermal nitroglycerin significantly increases exercise capacity in patients with stable angina, with an effect that is maintained over a 24-hour period using a single dose application. PMID- 3089075 TI - Observations on the use of oral sodium cromoglycate in a sulfite-sensitive asthmatic patient. PMID- 3089074 TI - Vasculitis presenting in an infant with agammaglobulinemia. PMID- 3089076 TI - [Percutaneous or surgical central catheters in the newborn infant]. AB - Central microcatheters are important in neonatal intestinal surgery, as peripheral veins are quickly all used up in these patients; they are essential in maintaining a satisfactory nutritional status during the period of digestive exclusion. This retrospective study over an 18 month period concerned 105 catheters (82 central percutaneous catheters and 23 surgical catheters) put up in neonates operated on within the first few days of life. The advantages and disadvantages of both methods of catheterization were assessed by means of the infectious or mechanical complications, as well as the length of time the catheters were used. The frequency, timing and type of mechanical incidents requiring removal of the catheter were the same for both groups. There was only one septic accident, and this with a surgical catheter. An analysis of the patient files helped to decide on the best route for use in central catheterization, as well as technical improvements. Because of the absence of infectious accidents in the percutaneous series, this method was preferred, especially as it has a certain number of advantages over the surgical method. Percutaneous central microcatheterization would appear well suited to medium term parenteral feeding. PMID- 3089077 TI - [Peranesthetic monitoring of ventilation in children: value of capnometry]. AB - Continuous measurement of the end-expiratory partial pressure of carbon dioxide (PETCO2) during anaesthesia has been proposed for non-invasive monitoring of arterial PCO2 (PaCO2). The values and the stability of the difference (PaCO2 PETCO2) during anaesthesia were studied for two ventilatory settings in eight children with healthy lungs and normal cardiac function undergoing minor surgery. PaCO2 values were all within a physiological range (30.2-43.6 mmHg). PaCO2-PETCO2 values ranged from 0.2 to 9.9 mmHg. With either mode of ventilation, there was no significant variation in PaCO2-PETCO2. It is concluded that estimation of PaCO2 was reliable during anaesthesia when haemodynamic and ventilatory states were stable, but a first determination of the PaCO2-PETCO2 gradient remained necessary for each child. PMID- 3089078 TI - [Bilateral prosthesis of the knee in a hemophilia A patient with an inhibitor]. AB - A forty-one year old severe haemophiliac A (factor VIII less than 1%) complicated by an antifactor VIII inhibitor was operated on for a bilateral arthroplasty of the knees. Substitutive treatment was started by giving anti-haemophilic A cryoprecipitate at a dose of 40 IU . kg-1. The anamnestic response occurred at day 6. Consumption of the inhibitor begun with the injection of 50,000 IU of concentrated factor VIII. This method proved to be insufficient for mastering the haemorrhagic syndrome, because the antibody titre quickly reached 10 IU Oxford. Treatment was continued with Autoplex (100 IU . kg-1), during three weeks, without any clinical or biological complications. It is suggested that Autoplex be used as the substitutive treatment in cases of major surgery in severe haemophilia complicated by a factor VIII inhibitor. PMID- 3089079 TI - [Tamponade and total parenteral nutrition by central venous catheter]. AB - Various complications are associated with the use of central venous catheters for total parenteral nutrition; cardiac tamponade is one of the most severe. Four cases are reported of cardiac tamponade during total parenteral nutrition: three of them were related to cardiac perforation by the tip of the catheter, placed in the right atrium; the fourth case may have been due to cardiac perforation or to an extraintestinal complication of inflammatory bowel disease. Hydropericardium may manifest itself soon after the catheter is inserted or, more usually, some days or weeks later. Immediate diagnosis is mandatory: a sudden and unexpected deterioration in a patient receiving total parenteral nutrition through a central venous catheter, with shock, heart failure, cyanosis, congestion of neck veins should arouse suspicion of hydropericardium. Long term undernutrition, a small atrophic heart, steroid treatment may also contribute to cardiac perforation. Immediate aspiration of the hydropericardium may be life-saving: if possible, the fluid is evacuated through the catheter while still in place; otherwise, pericardiocentesis must be immediately performed. Such complications can be prevented by: the use of flexible silicone or polyurethane catheters instead of rigid polyethylene catheters, especially for long term use; a correct positioning of the catheter tip in the superior vena cava in its extrapericardial sector, as it can be checked by chest X-ray. This examination, with opacification of the catheter with contrast medium, must be repeated because of the possibility of secondary displacement of the catheter. PMID- 3089080 TI - [Contracture test with ionophore A 23187 for the diagnosis of malignant hyperthermia]. AB - The results are reported of the contracture test obtained by using the calcium ionophore A 23187 (Calcimycin) in two patients, the son (A) and the mother (B). The past history of patient A revealed the occurrence of an impending malignant hyperthermia crisis during induction of anaesthesia in 1975. The A 23187 contracture test confirmed the presence of the malignant hyperthermia trait in patient A, whose muscle biopsy had been submitted to the caffeine contracture test, according to Ellis' technique, and found to be positive in the presence of 1 mmol of caffeine in the tissue bath; the contracture test could not be completed with a halothane contracture test, due to the impaired viability of the muscle fibres obtained. On the reverse, the mother (patient B) was found to be negative to the tests applied: the caffeine contracture test, the halothane contracture test and the contracture test performed with the calcium ionophore A 23187. It is suggested the A 23187 contracture test be added to the contracture tests as defined by the European Malignant Hyperpyrexia Group. This test could be of great help in identifying the percentage of relatives of MHS ("malignant hyperthermia susceptible") patients found to be MHE ("malignant hyperthermia equivocal"). PMID- 3089081 TI - Inaccuracy and expense of the leukocyte count in making urgent clinical decisions. AB - The care of 172 patients with abnormal white blood count (WBC) results was examined by chart review and physician interview. Neither the total leukocyte count, the neutrophil count, nor the band count reliably distinguished between bacterial, nonbacterial, and noninfectious disease. The positive predictive value for bacterial disease of a WBC greater than or equal to 12,500/mm3 was only 26%, with either a neutrophil count greater than or equal to 10,000/mm3 or a band count greater than or equal to 500/mm3, the positive predictive value was only 33%. Of WBCs, 21% were ordered by mistake when another (or no) test was desired. Only 18 abnormal WBCs of 172 (10.4%) (of the total 860 obtained) had any impact on the patient's clinical management, and only ten caused impact judged to be neutral or beneficial. Based on a WBC and differential costs of +23.50, obtaining an abnormal result that had a clearly beneficial impact on patient care would cost +10,105 in unneeded tests. The WBC does not in itself reliably predict severity or cause of disease in acutely ill adults, and its widespread use as a screening test in this setting probably should be abandoned. PMID- 3089082 TI - Preliminary evidence for a diagnostic immunoglobulin G1 antibody response among culture-positive cows vaccinated with Brucella abortus strain 19 and challenge exposed with strain 2308. AB - The sera of cows inoculated with Brucella abortus have a characteristically high titer of immunoglobulin (Ig) G1 antibodies to a soluble brucella antigen compared with sera of noninoculated vaccinated cattle. Concentrations of antigen-specific IgG1 were greater than 10-fold higher than those for IgG2, even though total IgG2 concentrations were higher than total IgG1 concentrations. Increases in IgG1 antibodies to Brucella abortus soluble antigen were detected shortly after vaccination in those cows from which strain 19 was isolated and by 28 weeks in cows from which strain 2308 was isolated. Increases in specific antibodies were not paralleled by increases in either total IgG1 or total IgG2 concentrations. Rather, there was a 15-fold to greater than 200-fold increase in specific activity, with up to 16% of the IgG1 specific for the brucella antigen used in the assay. Thus, measurement of changes in total IgG1 concentrations is not a reliable method to identify brucellosis-associated anti-Brucella abortus soluble antigen activity. Only one cow in a panel of 10 selected for detailed study showed a false-positive IgG1 titer, whereas some serologic assays showed as many as 4 or 5 false-positives. Results of the complement-fixation test, among the battery of serologic tests used for detection of brucellosis, best agreed with the occurrence of increased IgG1 antibody levels. PMID- 3089083 TI - Endotoxin-induced bovine mastitis: arachidonic acid metabolites in milk and plasma and effect of flunixin meglumine. AB - Arachidonic acid metabolites (AAM) were measured in milk and plasma during the course of acute endotoxin-induced mastitis in 12 lactating cows. Mastitis was induced by intramammary challenge exposure with 10 micrograms of Escherichia coli (026:B6) endotoxin. Endotoxin was injected into the teat cistern via the teat canal of a single randomly selected rear quarter of each cow. Concentrations of prostaglandin (PG) F2 alpha and thromboxane (Tx) B2 in fat-free unextracted milk and of 15-keto-13,14-dihydro-PGF2 alpha in plasma were measured by radioimmunoassay. Total production of AAM in milk was determined by measuring quarter milk production. The AAM were compared in 6 cows administered flunixin meglumine (1.1 mg/kg of body weight) and in 6 cows administered saline solution. Concentrations of TxB2 in milk were significantly (P less than 0.001) increased during the early course of acute mastitis in endotoxin-treated quarters of cows not administered flunixin meglumine. Peak concentrations of TxB2 in milk occurred at 8 hours after endotoxin inoculation. Flunixin meglumine treatment produced significant (P less than 0.05) reductions in milk TxB2 and plasma 15-keto-13,14 dihydro-PGF2 alpha concentrations. Concentrations of PGF2 alpha in milk and total PGF2 alpha and TxB2 production per quarter per milking were not significantly influenced by endotoxin challenge or by flunixin meglumine treatment. PMID- 3089084 TI - Ambulatory surgery. Its impact on general surgical practice. PMID- 3089085 TI - Pneumothorax from nasoenteric feeding tube insertion. A report of five cases. AB - This report describes five patients who developed pneumothorax following misplacement of a nasoenteric feeding tube. Three of the patients required tube thoracostomy. Of these, one was subsequently discharged; one required two chest tubes, yet died 2 days later; the third patient developed a chronic empyema that ultimately required chest wall reconstruction for resolution. The development of pneumothorax from nasoenteric feeding tube misplacement was influenced by the type of tube and the general characteristics of the patients. The use of a cuffed endotracheal tube did not afford protection against misplacement. The significant morbidity and mortality associated with pneumothorax following nasoenteric feeding tube insertion argue for careful evaluation of the clinical setting when considering enteral nutritional support with a nasoenteric feeding tube. PMID- 3089086 TI - Cost-effectiveness of culturing for Chlamydia trachomatis. A study in a clinic for sexually transmitted diseases. AB - We have evaluated the cost-effectiveness of using cell culture to test for chlamydial infections in 9979 patients at a clinic for sexually transmitted diseases. From results of cultures, we have established prevalence data and, using decision-theory analysis, have calculated costs and probabilities of various outcomes. According to their histories and presenting signs and symptoms, patients were classified as at high or low risk for chlamydial infections. Empiric treatment of all patients attending the clinic was the most cost effective strategy, followed by empiric treatment of high-risk women and culture based treatment of low-risk women. Obtaining cultures for men at high and low risk was not cost-effective. If universal treatment is not provided, the most cost-effective strategy appears to be empiric therapy in patients at high risk for chlamydial infections and therapy based on diagnostic test results in women at low risk. PMID- 3089087 TI - Mental deficiency in pseudohypoparathyroidism type I is associated with Ns protein deficiency. AB - Pseudohypoparathyroidism type I is a hereditary disorder characterized by resistance to parathyroid hormone and other hormones that work via cyclic adenosine 3', 5'-monophosphate (cAMP). Most patients with this disorder have generalized deficient activity of Ns-protein (type Ia), which couples stimulatory hormone receptors to catalytic adenylate cyclase. In patients with normal Ns protein activity (type Ib), a decreased incidence of resistance to hormones other than parathyroid hormone exists. Mental deficiency of unknown cause occurs in 47% to 75% of all patients with pseudohypoparathyroidism type I. Because mutations in the adenylate cyclase-cAMP system may affect the learning ability of Drosophila flies, we assessed mental deficiency in 25 patients whose Ns-protein activity we had determined: 9 of 14 patients with type Ia disorder and 0 of 11 patients with type Ib disorder had mental deficiency. We suggest that Ns-protein deficiency, reduced cAMP levels, or both, are involved in the mental deficiency in these patients and probably in mental function in humans. PMID- 3089088 TI - Unstable angina associated with factor VIII concentrate therapy for hemophilia A. PMID- 3089089 TI - Thyrotoxicosis presenting with secretory diarrhea. PMID- 3089091 TI - Paradoxical marker of non-A, non-B hepatitis. PMID- 3089090 TI - Auranofin: a new drug for rheumatoid arthritis. PMID- 3089092 TI - The acquired immunodeficiency syndrome and lupus anticoagulant. PMID- 3089093 TI - Intravenous nitroglycerin and heparin resistance. PMID- 3089094 TI - The role of lysyl, arginyl, and sulfhydryl residues in estrogen receptor activation, 4S to 5S dimerization, and conversion of receptor from a state with low affinity into a state with higher affinity for estrogen. PMID- 3089095 TI - Breast cyst fluid proteins and breast cancer. AB - A specific breast cyst fluid protein was purified by the following steps: ultracentrifugation, gel filtration, DEAE and Con A chromatography, and gel filtration with guanidine, 6 M. The protein was pure, having a molecular weight of 17,800 daltons on SDS-PAGE and 68,000 daltons on gel filtration. The GCDFP 17,800 is immunologically distinct from other breast cyst fluid components and known milk and plasma proteins. A specific radioimmunoassay was developed and used to determine GCDFP 17,800 in 158 samples of breast cancer cytosol. The GCDFP 17,800 levels were significantly different between grade I tumors (mean of 813 ng protein per mg +/- 430 SEM) and grade III tumors (mean 184 ng protein per mg +/- 59 SEM) and were correlated with progesterone receptor values in postmenopausal women (Spearman's correlation, p = 0.03) but not in premenopausal women. The value of GCDFP 17,800 did not differ between the pre- and the postmenopausal women. By immunocytochemistry the intracellular localization of the GCDFP 17,800 was also found in relation to tumor grading and in correlation with PR values. GCDFP 17,800 appears as a hormone-induced protein of the breast cells. Its intracellular detection by means of radiolabeling allows a more sensitive and precise evaluation of the hormone-dependence of the breast cancer cells and emphasizes the heterogeneity of the tumor cell population. PMID- 3089096 TI - Current status of hormonal therapy of fibrocystic breast disease. PMID- 3089097 TI - The pituitary gland in primate mammary development: evidence that prolactin is not essential. PMID- 3089098 TI - Relation between risk of breast cancer and biological availability of estradiol in the blood: prospective study in Guernsey. PMID- 3089099 TI - Immunoglobulin G subclasses in sarcoidosis. PMID- 3089100 TI - Genetic control of macrophage responses. AB - A short review of current concepts concerning the origin and kinetics of monocytes and macrophages is given, and the humoral regulation of monocyte production by FIM, a factor synthesized and secreted by macrophages, is discussed. Genetic control of the responsiveness of monocyte precursors to FIM and that of the phagocytosis and intracellular killing of bacteria is dealt with. PMID- 3089101 TI - Enhanced inflammatory response with histiocytes and epithelioid cells in rabbits to the intradermal injection of supernatants of cultured cutaneous sarcoidal granulomas. AB - This study was designed to examine the inflammatory response in rabbits to intradermal injections of lymphokine-containing supernatants from cultured cutaneous sarcoidal granulomas (sarcoidal supernatant). Cell-free sarcoidal supernatants and concurrently incubated culture medium controls, alone or mixed with heat-inactivated K-S antigen or BLB, were injected intradermally into rabbits. These were, compared to control results, increased inflammatory reactions with histiocytes and epithelioid cells at the injection sites in 9 out of 11 experiments using sarcoidal supernatants mixed with K-S antigen and in 8 out of 10 experiments with these supernatants mixed with BLB. Sarcoidal supernatant alone, control medium, or normal saline solution produced no inflammatory response. Supernatants from cultured normal skin tissues obtained from sarcoid patients and those obtained from surgical patients free of sarcoidosis, when mixed with K-S antigen or BLB, showed variable inflammatory responses similar to the response seen with sarcoidal supernatants, but these were not significantly different from those of their own controls. It was concluded that lymphokines released locally may initiate and maintain the formation of sarcoidal granulomata. PMID- 3089102 TI - Quantitation of cutaneous Langerhans' cells of sarcoidosis patients. PMID- 3089103 TI - Immunoregulation of granuloma formation in murine schistosomiasis mansoni. AB - Schistosomiasis mansoni is a chronic, T lymphocyte-mediated granulomatous disease that affects mainly the liver and intestines of the infected host. The chronic inflammatory process and subsequent fibrous repair are the major factors in the pathology of the disease. In the murine model of schistosomiasis at the onset of the chronic stage of the infection, the granulomatous response undergoes spontaneous modulation with concomitant alleviation of the pathologic disturbance. Analysis of the process of modulation revealed that it results from the interaction between inflammatory and regulatory subpopulations of T lymphocytes. At the acute phase of the infection, the granulomatous response is initiated and maintained by inflammatory TDH cells that release lymphokines which mobilize and recruit the macrophages, eosinophils, etc. for the generation of the lesion. Already at this stage, while the inflammatory influence prevails, a low number of suppressor T lymphocytes are present. With the progress of the infection, the overheated inflammatory response is curbed by regulatory processes. At least two, but perhaps more, T suppressor lymphocytes are involved in the maintenance of the modulation of the granulomatous response. Modulation is an active process that needs constant maintenance, probably by recruitment of fresh suppressor cells. Removal of the suppressor population causes an immediate elevation of the granulomatous response. During modulation, T suppressor lymphocytes either abrogate or greatly diminish inflammatory lymphokine production. This in turn may be the cause for decreased cell recruitment and diminution in newly formed granuloma size. Apparently a total abrogation of the granulomatous response is not desirable because released egg antigens can be harmful to liver parenchyma cells. This has been demonstrated both in thymus deprived and in nude, infected mice. Thus, a smaller inflammatory response has the double advantage of not only being less destructive, but also shielding the underlying tissue from damage by parasite products. The various subpopulations of T lymphocytes communicate with one another by means of soluble suppressor factors that arise from the suppressor T cells. The factors may have different functions. One factor may regulate lymphokine production whereas another may recruit fresh suppressor cells from a pool of precursors. The factors act in an antigen specific manner. Tentatively, one may assume that these factors are composed of two units: one is the I subregion membrane marker and the other is the specific recognition receptor. The nature of this receptor is still unclear, but it may be an anti-idiotypic determinant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3089104 TI - In vitro granuloma formation using defined antigenic nidi. AB - The in vitro granuloma model provides an excellent tool to study granulomatous hypersensitivity. In our studies of granuloma formation in schistosomiasis, we have demonstrated the utility of the model with respect to analysis of human PBL responses, cloned T cells, purified antigens of the parasite, and regulatory mechanisms. We have also presented data which demonstrate the applicability of this model to other antigenic systems. While the suggestion that this model may be suitable for the study of sarcoidosis may be premature, we would propose that the system may be adapted to screen potentially causative antigens. Furthermore, with the identification of the critical antigen(s), the in vitro granuloma model will facilitate studies at the clinical level. PMID- 3089105 TI - Differential localization of MAP-2 and tau in mammalian neurons in situ. PMID- 3089106 TI - The binding of MAP-2 and tau on brain microtubules in vitro: implications for microtubule structure. AB - We have presented data that indicate that MAP-2 associates with brain microtubules at nonrandomly distributed sites, whose distribution on the microtubule polymer can best be described by the 12-dimer MAP superlattice originally described by Amos; because of the additional spacings, however, between MAP-2 projections observed on MAP-2-saturated microtubules, we suggest that the 6-dimer MAP superlattice, or what we will call the double Amos superlattice, more completely specifies the total set of MAP-binding sites on cytoplasmic microtubules. Second, we have shown that brain microtubules reassembled in vitro contain a heterogeneous population of MAP-binding sites, which differ in their affinities for the two MAPs, MAP-2 and tau. Third, we have shown that microtubule populations that differ in their MAP content have subtle, but detectable differences in their tubulin isotype composition. Based on all the data presented here, we have presented the idea of a nonrandom distribution of tubulin isotypes within a microtubule as a means by which a cell could specify both the identity and the distribution of MAP-binding sites. PMID- 3089107 TI - Tau microheterogeneity: an immunological approach with monoclonal antibodies. AB - The family of tau polypeptides purified from mammalian brain exhibit both extensive heterogeneity and large similarities in their chemical, physical, and functional properties. All the tau isoforms generated at a transcriptional or posttranscriptional level share the property of interacting with tubulin dimers in a specific manner. They strengthen longitudinal interactions between tubulin dimers and thus may stabilize microtubules once they are formed. Mild proteolysis or phosphorylation does not remove but only modulates the tau specific function that is probably related to the conserved sequences of the molecules. Monoclonal antibodies raised against tau were found to recognize epitopes conserved not only between species but also in different tissues. Using indirect immunofluorescence, a specific staining pattern was observed on rat neuronal cells and also on human skin fibroblasts. The same antibodies did not recognize glial cells, suggesting that these cells either do not contain detectable levels of tau or contain tau molecules different from the neuronal ones. These data suggest that tau protein is widely distributed, highly conserved, and may be preferentially associated with special subclasses of microtubules. PMID- 3089108 TI - Association of calcium/calmodulin-dependent kinase with cytoskeletal preparations: phosphorylation of tubulin, neurofilament, and microtubule associated proteins. AB - Calcium and calmodulin have been implicated in the regulation of cytoskeletal function. In this report, we demonstrate that microtubule preparations from rat brain contain a calcium/calmodulin-dependent protein kinase that phosphorylates endogenous MAP-2, tubulin, synapsin I, and neurofilament proteins. This cytoskeletal-associated kinase has been biochemically characterized and shown to be identical to Type II calcium/calmodulin-dependent protein kinase (CaM kinase II). The subunits of CaM kinase II represented major calmodulin-binding proteins in cytoskeletal preparations. A monoclonal antibody against the 52000 Da subunit of CaM kinase II specifically labeled cytoskeletal elements in cortical neurons. These results indicate that CaM kinase II is associated with the neuronal cytoskeleton and may play a role in mediating some of the effects of calcium on cytoskeletal function. PMID- 3089109 TI - The calcium sensitivity of MAP-2 and tau microtubules in the presence of calmodulin. PMID- 3089110 TI - Microtubule-associated proteins. In vitro isolation versus in vivo function. PMID- 3089111 TI - Microtubule-associated proteins (MAPs) of dogfish brain and squid optic ganglia. PMID- 3089112 TI - The role of Lys 394 in microtubule assembly. PMID- 3089113 TI - Opioid and catecholaminergic mechanisms of different types of analgesia. PMID- 3089114 TI - A new immune monitoring system for the determination of lymphoid cell subsets. PMID- 3089115 TI - Characteristics of monoclonal antibody measurements in human peripheral blood. AB - Three areas of monoclonal antibody measurements using flow cytometry have been presented. These include a description of a dual immunofluorescent method for measuring two antibodies simultaneously, the effects of blood storage on enumeration of helper (H) and suppressor (S) cells, and the relationship between absolute lymphocyte count and H/S ratio in both control and AIDS patients. These studies reveal that a dual immunofluorescent labeling method is useful for enumerating lymphocytes from peripheral blood which bear the helper, suppressor and/or thymus-derived (T) cell receptors. Fluorescein (FL)-conjugated Leu-3a + 3b antibodies were used to enumerate helper T-lymphocytes, while the B-phycoerythrin (B-PE)-conjugated Leu-2a antibodies were utilized for enumerating suppressor T lymphocytes. Dual immunofluorescently stained lymphocytes, prepared from whole blood, were analyzed by flow cytometry. Two light scatter parameters, (forward and 90 degree scatter) were used to define the lysed erythrocyte, lymphocyte, monocyte, and granulocyte populations. Only the lymphocytes were analyzed for dual immunofluorescence activity. The helper and suppressor distributions from 167 control patients were as follows: The average percentage +/- SD of the helper and suppressor cells were 42.8 +/- 7.5 and 21.6 +/- 6.4, respectively. The H/S ratio was 2.17 +/- .75. These studies show that the H/S ratio can be determined in a single preparative sample and analyzed by dual immunofluorescence in a single flow cytometric analysis even though the H/S ratio may vary from normal during a disease condition. The dual immunofluorescent assay enables one to correlate the activities of two antibodies against cell surface receptors and allows the measurement of a large number of samples in a minimal time. This study also compared the effects of anticoagulant, storage time, and temperature on the phenotypic determination of the percentages of helper and suppressor T lymphocytes in human peripheral blood. Blood was drawn in ACD, heparin, and EDTA and stored for up to 4 days at room temperature or 4 degrees C. Phenotypic determination of helper/suppressor lymphocytes was most stable for ACD or heparinized blood at room temperature. Marked changes were observed in the percentages of helper cells at 4 degrees C, whereas the percentages of suppressor cells did not change appreciably regardless of the anticoagulant storage time or temperature. Finally, the relationship between ALC and the H/S ratio in control and AIDS patients was determined. The ALC varied considerably in both control and patient populations as a function of time. Conversely, the H/S ratio remained constant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3089116 TI - Detection of minimal residual disease in acute leukemia by flow cytometry. AB - Commercial flow cytometers can detect and enumerate rare cells at the level of 1 per 10(5) other cells within a reasonable measuring time, provided that the rare cells can be uniquely labeled with fluorescent marker. This detection level is sufficient for the enumeration of normal hematopoietic stem cells and committed progenitor cells. Detection at this level is useful for the quantitation of residual leukemic cells in remission bone marrow, for the analysis of the proliferative state of these cells as well as of normal stem cells, which are of importance in choosing the optimal chemotherapy regimen, and for monitoring the efficacy of maintenance chemotherapy. A further improvement in the speed of flow cytometers would be required, however, to make full use of the bone marrow samples. PMID- 3089118 TI - Assessment of leukocyte alkaline phosphatase by image analysis. AB - We have shown that it is possible to automate the assessment of leukocyte alkaline phosphatase by using an azo dye cytochemical staining procedure and a commercial, highly sophisticated image analysis instrument originally designed specifically as a differential white cell counter. The data to date indicate that values obtained by this approach are at least as precise and accurate as current manual techniques. Instrumental analysis avoids the subjectivity associated with manual interpretation of staining intensity and should permit meaningful interlaboratory comparisons. The stability of the stained smears upon exposure to immersion oil or Polymount mounting medium proved to be an unexpected bonus. In addition to such functional data on leukocytes as illustrated by this report, these instruments, with appropriate staining methods and software, can also provide clinically useful quantitative data on red cells, as have been described for reticulocytes. We hope to see more clinical applications in the future for these expensive and target-oriented image analysis instruments. They are capable of automatically providing objective quantitative information on a cell by cell basis--providing feature data that cannot be obtained by other means. PMID- 3089117 TI - Flow cytometric analysis of cell kinetic responses using measurements of correlated DNA and nuclear protein. PMID- 3089119 TI - Controls for flow cytometers in hematology and cellular immunology. AB - The necessity of using freshly prepared biological samples to control and calibrate flow cytometers has impeded the utilization of flow cytometry in the clinical laboratory where regulations demand careful control calibration and yet workload and technician training militate against the preparation of specialized control samples. For a number of years, cell preparations with stabilized properties have been used routinely in hematology laboratories to evaluate the daily performance of automated blood cell counters including optical flow cytometers. Unfortunately, the stabilized preparations do not necessarily duplicate many important aspects of whole blood, resulting in variable performance of a given control preparation on different types of instrumentation. The new generation of hematology analyzers measures a host of new parameters and will require more sophisticated controls for these enhanced parameters. Some practical aspects of present and future hematology controls will be discussed. Immunology, a new area for automated cell analysis, can benefit greatly from controls both for instrument performance and for cell staining. Up to this time there has been little availability of control materials suitable for clinical immunology. We have been evaluating fluorochrome-stained cell nuclei for use as an instrument control and for calibration of immunofluorescence analyses. Our development and use of this type of control will be described. We will also discuss approaches and experiments aimed at producing cells with stabilized antigenic properties which can be stained with monoclonal antibodies and can thus act as actual reagent controls. PMID- 3089120 TI - Immobilization of beta-galactosidase in porous supports. PMID- 3089121 TI - Design and operating strategies for immobilized living cell reactor systems. Part I. Biosynthesis of candicidin. PMID- 3089122 TI - Design of sequence-specific DNA cleaving molecules. Comparison of distamycin-EDTA X Fe(II) and N-bromoacetyldistamycin. PMID- 3089123 TI - The metabolic consequences of infusing emulsions containing medium chain triglycerides for parenteral nutrition: a comparative study with conventional lipid. AB - In order to test the hypothesis that medium chain triglycerides (MCT's) are a safe and potentially superior energy source during parenteral nutrition 13 patients were entered into a randomised cross over trial. They received either a long chain triglyceride emulsion (LCT) or a 50% medium chain (MCT)/50% LCT mixture as part of their energy supply. Nitrogen balance was significantly better when MCT/LCT was infused and the greater levels of plasma ketones and lower plasma triglyceride levels suggested that MCT was more readily metabolised in these patients. Routine haematology, biochemistry and liver function tests gave no indication of harmful side effects from MCT. PMID- 3089124 TI - Macrophage activation. Introduction. PMID- 3089125 TI - Intracellular activation of tumoricidal properties in mouse macrophages and human monocytes by recombinant mouse or human gamma interferon encapsulated in liposomes. PMID- 3089126 TI - Molecular bases for macrophage activation. PMID- 3089127 TI - Activation of hybridoma macrophages. PMID- 3089128 TI - [Cancer of schistosomiasis-infected bladders. Apropos of 6 cases]. AB - It is a well known fact that patients with urinary schistosomiasis are at risk for carcinoma of the bladder. Although relatively few cases are seen in France. Among 130 patients with urinary schistosomiasis hospitalized in our department from April 1980 to December 1984, 6 cases of carcinoma of the bladder were diagnosed. Our series has a number of specific characteristics: patients are Black Africans, and the anatomoclinical characteristics of these tumors differ from those found in vesical tumors in Europeans free of schistosomiasis, with, apparently, a greater sensitivity to chemotherapy. PMID- 3089130 TI - The moral foundation of nursing. PMID- 3089129 TI - Violence and the health care "family". PMID- 3089131 TI - Toward a nursing definition of child maltreatment using seriousness vignettes. AB - To determine whether nurses operationally define child maltreatment in a like manner regardless of their practice specialty, eight practice groups (N = 596) participated in a mail survey. The survey allowed nurses to judge the potential seriousness of child maltreatment incidents. Multivariate statistical analyses revealed significant group differences. Follow-up analyses of variance (ANOVAs) revealed a difference between anesthetists and community health nurses on one factor (parental sexual mores). However, an investigator-developed scale demonstrated the differences would lack substantive value in clinical practice. It was concluded that nursing specialty groups define similarly the seriousness of child abuse and neglect despite varied backgrounds. PMID- 3089132 TI - Father-daughter incest: immediate and long-term effects of sexual abuse. AB - The characteristics, immediate and long-term aftereffects, and methods of adapting to father-daughter incest were examined. Twenty-one women with a past history of childhood or adolescent paternal incest were interviewed. The findings suggest that the female victim of paternal incest may endure more emotional, social, physical, self-identity, familial, and interpersonal difficulties during and shortly after the incest has been terminated. Relationships with men and sexuality were more adversely affected with time. Positive coping mechanisms of incest and factors contributing to the victims' adjustment to the incest were documented. Implications of findings for nursing practice and research are discussed. PMID- 3089133 TI - Nursing assessment for risk of homicide with battered women. AB - The Danger Assessment is a clinical and research instrument that has been designed to help battered women assess their danger of homicide. Completing the Danger Assessment with a nurse is conceptualized as a means of increasing the self-care agency of battered women, according to Orem's nursing conceptual framework. The instrument was used in a study of 79 battered women. Results of this study, which give initial support for the reliability and validity of the Danger Assessment, are reported. The instrument is available from the author on request. PMID- 3089134 TI - Research and practice with abused women: use of the Roy adaptation model as an explanatory framework. AB - Roy's adaptation model and its utility as a conceptual framework for research and clinical practice with abused women is described through research and clinical examples. The research with a sample of 40 abused women focuses on their help seeking patterns, whereas the clinical practice with a larger sample focuses on the interrelationships of the constructs. The apparent strengths and weaknesses of Roy's model are discussed. Based on this critique, specific modifications are made, and propositions suggested, for follow-up studies and intervention. PMID- 3089135 TI - Caring for the frail elderly at home: toward a theoretical explanation of the dynamics of poor quality family caregiving. AB - Using the grounded theory approach, 39 family caregivers were theoretically sampled using newspaper advertising to explore their perceptions of providing home care for frail elders and to generate a theoretical model that describes the dynamics of good quality and poor quality family caregiving; explains the relationships among certain contextual and perceptual variables and the behaviors exchanged by elders and caregivers; and identifies points where interventions by nurses could be effective. The model consists of five constructs that were identified from the data and were staged within the framework provided by symbolic interactionism and social exchange theory. The five constructs and two related driving forces provide a partial explanation for the quality of family caregiving and a beginning explanation for the phenomenon of elder abuse. PMID- 3089136 TI - [3-component nutrient medium for the nisin producer Streptococcus lactis strain MGU]. AB - The methods of mathematical desing of experiments such as Box and full factorial design were used in the study. As a result a three-component medium including 1-2 per cent of mollases, 10-20 mg% of yeast autolysate and 1-2 per cent of KH2PO4 was recommended for biosynthesis of nisin. PMID- 3089137 TI - [Effect of antibiotics on the adhesive properties of microorganisms and an available model for its study]. AB - The effect of benzylpenicillin, ampicillin, bicillin-3, carbenicillin, levomycetin, erythromycin, streptomycin and kanamycin on the adhesive properties of 9 test microbes including 5 strains of Lactobacillus from human microflora, 3 uropathornic strains of E. coli and 1 strain of S. aureus was studied with the method developed by the authors. The method is based on the use of formalinized human erythrocytes as macroorganism cells. It was shown that the antibiotic inhibitory effect on adhesion depended on mechanism of action of the antibiotics and their concentration, was associated with the level of the microbial adhesion and did not depend on the microbial sensitivity to the drugs. PMID- 3089138 TI - [Significance of cellular pharmacokinetic data in predicting antibiotic activity in body cells: comparative research on preparations acting on Pseudomonas aeruginosa]. AB - Penetration of carbenicillin, cefotaxime, gentamicin and sisomicin into leukocytes of peripheral blood in man and their intracellular distribution were studied. By its capacity for penetration into leukocytes cefotaxime was superior to the other antibiotics. The levels of sisomicin and carbenicillin absorption by the cells were equal. The level of gentamicin penetration into the cells was the lowest. After penetration into the cells the main part of carbenicillin was preserved in its active form in the cytoplasm. Absorption of the antibiotic by the nuclei, granules, mitochondria and microsomes was insignificant. Cefotaxime was bound to the organoids and not more than 20 per cent of the antibiotic were preserved in its active form. The aminoglycosides were mainly absorbed by the cell granule fraction and the level of the active form of sisomicin in the cytoplasm was twice as higher as that of gentamicin. On the basis of the data on the cell pharmacokinetics of the above antibiotics, their mean therapeutic serum levels and mean geometric values of their MICs for P. aeruginosa it was suggested that in case of intracellular localization of P. aeruginosa the increase in the antibiotic efficacy was of the following order: gentamicin less than cefotaxime less than or equal to sisomicin less than carbenicillin. PMID- 3089139 TI - Characterization of NPS-1, a novel plasmid-mediated beta-lactamase, from two Pseudomonas aeruginosa isolates. AB - A novel beta-lactamase, which had a pI of 6.5 and a molecular weight of 25,000, was observed in two Pseudomonas aeruginosa isolates. The enzyme, designated NPS 1, was encoded by a plasmid of molecular weight 41 X 10(6) which also encoded resistance to streptomycin and sulfonamide. This plasmid, designated pMLH50, was freely transmissible to other P. aeruginosa strains, but not to Escherichia coli K-12. The enzyme was purified partially and shown to have activity against both penicillins and cephalosporins. Vmax rates for oxacillin and carbenicillin were less than 50% of the Vmax for benzylpenicillin, and the Vmax for cephaloridine was only 3% of the Vmax for benzylpenicillin. Imipenem, aztreonam, and several antipseudomonal cephalosporins were stable to the enzyme. Hydrolysis of most substrates obeyed Michaelis-Menten kinetics, but cefsulodin induced a reversible reduction in the activity of the enzyme. Transconjugants of the beta-lactamase producing isolates in P. aeruginosa PU21 acquired beta-lactam resistances which mirrored the hydrolytic activity of the enzyme. PMID- 3089140 TI - Artifacts in dilution pharmacokinetic models caused by adherent bacteria. AB - Liquid cultures of a Pseudomonas aeruginosa strain in Mueller-Hinton broth diluted at rates higher than the bacterial growth rate showed the expected decrease in CFU only for 1 to 2 h. Later the CFU started to increase. This phenomenon can be explained by a hypothesis that assumes that the bacteria multiply in two different compartments. From the first compartment, which comprises bacteria homogeneously distributed in the broth, cells are eliminated at a rate that is dependent on the dilution and growth rates. Concomitantly, the second compartment is formed as a nondilutable adherent population on the surface of the culture vessel. Eventually, only cells stemming from that population appeared in the medium and were subsequently diluted. This hypothesis can be described mathematically by a linear combination of two exponential functions. The calculated values fit the experimental data well. Because similar CFU versus time curves were also found with other strains, care should be taken in interpreting results of experiments performed in liquid cultures and evaluated in terms of CFU. One should bear in mind that within a liquid culture an adherent population may exist, which differs in size according to selective influences (dilution, addition of antibiotics, etc.). This may give rise to artificial and unexpected results. PMID- 3089141 TI - Evaluation of the bactericidal activity of beta-lactam antibiotics on slowly growing bacteria cultured in the chemostat. AB - The bactericidal activity of 23 beta-lactam antibiotics was compared in slowly growing bacteria cultured in a chemostat. In an attempt to mimic possible in vivo conditions, slowly growing cultures were produced by limitation of iron, glucose, phosphate, or magnesium. Only select antibiotics remained effectively bactericidal against slowly growing cells. For these compounds, the rate of antibiotic-induced loss of viability was a constant when killing was expressed per generation (in contrast to absolute time) in that slowly growing bacteria were killed proportionately more slowly. Individual antibiotics differed greatly, however, in their specific bactericidal activities against slowly growing cells, i.e., in the absolute degree of killing elicited during exposure of the bacteria to MIC equivalents of the drugs. Specific bactericidal activities varied not only with drug structure but also with the bacterial strains and, to a lesser extent, with the nature of the growth-limiting nutrient. In slowly growing cultures exposure to the low drug concentrations studied here (near MIC) caused killing without detectable lysis. Antibiotics with high specific bactericidal activities were capable of rapidly killing cultures of slowly growing pathogens despite extremely long generation times approaching those reported for in vivo growth rates. PMID- 3089142 TI - Dose ranging study of cefpimizole (U-63196E) for treatment of uncomplicated gonorrhea in men. AB - We conducted a two-center dose ranging study to evaluate the efficacy, tolerance, and toxicity of cefpimizole, a new cephalosporin, in the treatment of uncomplicated gonorrhea in 96 males. Twelve patients at each center were treated intramuscularly with single doses of 1.0, 0.5, 0.25, and 0.125 g of cefpimizole. All urethral infections were cured at the highest dose, but lower doses produced progressively decreasing cure rates of 90% (0.5 g), 83% (0.25 g), and 71% (0.125 g). Treatment failures of rectal and pharyngeal infections occurred at the highest dose level. Geometric mean MICs for cefpimizole for successfully and unsuccessfully treated volunteers were 0.088 and 0.282 micrograms/ml, respectively. A prominent adverse effect was clinically significant pain at the injection site, which occurred in 57 (59%) of 96 patients. Results of the study demonstrate that cefpimizole offers no advantage over currently available antibiotics in the treatment of uncomplicated gonorrhea in men. PMID- 3089143 TI - Effect of amiloride on the intracellular sodium and potassium content of intact Streptococcus faecalis cells in vitro. AB - Amiloride at millimolar concentrations caused marked changes in the growth dependent intracellular balance of Na+ and K+ in Streptococcus faecalis. These results, whether specific to transport processes or resulting from indirect yet unknown mechanisms, constitute the first evidence of an effect of amiloride on bacterial electrolytes. PMID- 3089144 TI - Previously undescribed 6.6-kilobase R plasmid in penicillinase-producing Neisseria gonorrhoeae. AB - A penicillin-resistant Neisseria gonorrhoeae strain was isolated. The resistance was due to the production of TEM-1 beta-lactamase encoded by a plasmid. This 6.6 kilobase plasmid was compared with the previously known 7.4- and 5.3-kilobase penicillin R plasmids of N. gonorrhoeae. PMID- 3089145 TI - Operating room scheduling. A literature review. PMID- 3089146 TI - Survey: statewide family support programs. AB - Results of a survey of 23 state conducted family support programs are presented. Sixteen programs are legislatively mandated and the majority have a similar purpose: reduction of out-of-home placements. However, great variability exists on eligibility criteria, methods of program administration, amount of support, and types of services provided. Program evaluation data are reviewed indicating that cost-benefits, decreased rates of out-of-home placement, and effects on family enhancement are primary concerns of these programs. Implications for future program development based upon normalization philosophy and stress/coping theories are presented. PMID- 3089147 TI - Selective-enrichment procedure for isolation of Listeria monocytogenes from fecal and biologic specimens. AB - A selective-enrichment procedure (SEP) was developed to isolate Listeria monocytogenes from fecal and biologic specimens. This procedure was compared with direct plating with McBride listeria agar and 2-, 4-, and 8-week cold-enrichment procedures in recovering L. monocytogenes from mouse fecal, liver, and brain specimens. Although the SEP occasionally did not isolate the organism from specimens proved positive by the other procedures, the SEP isolated L. monocytogenes from about two and five times as many specimens as the cold enrichment and direct-plating procedures, respectively. PMID- 3089148 TI - Effect of salinity gradients and heterotrophic microbial activity on biodegradation of nitrilotriacetic acid in laboratory simulations of the estuarine environment. AB - The biodegradation of nitrilotriacetic acid (NTA), a synthetic replacement detergent builder, in the estuarine environment was examined by using a laboratory estuarine simulation. Two interdependent microcosms were used; each of five vessels was equilibrated with a saline gradient between 1.30 and 17.17%, with the final vessel subsequently being increased to a maximum salinity of 31.6%. Each microcosm was seeded simultaneously with heterotrophic bacteria from both fresh and saline sources. Viable counts demonstrated the ability of each microcosm to sustain a mixed heterotrophic bacterial community throughout the range of salinities for 183 days after a stabilization period. Isolation studies demonstrated that both systems contained four bacterial species, representatives of the genera Vibrio and Flavobacterium and members of the coryneform group and the family Enterobacteriaceae. Total bacterial numbers and species diversity decreased with increased salinity. NTA was administered at low and high concentrations, one concentration to each microcosm, initially with the least amount of saline. Removal of both concentrations of NTA occurred and was attributed to biodegradation after a period of bacterial acclimatization. Subsequent dosing of NTA to vessels of higher salinity demonstrated that biodegradation was incomplete at observed mean salinities of greater than 9.18% at low influent NTA concentrations and greater than 5.08% at high influent NTA concentrations. Therefore, acclimatization was dose dependent. It was concluded that NTA acclimatization at the higher salinities ceased because of salinity stress-induced failure of NTA catabolism and not the disappearance of a particular bacterial species. PMID- 3089149 TI - Pattern recognition analysis of in vivo enzyme-substrate fluorescence velocities in microorganism detection and identification. AB - A spectrometric technique is presented that combines most of the important criteria necessary for efficient detection and identification of microorganisms. These criteria include simplicity of experimental design, various degrees of sensitivity and selectivity, convenience, and total reaction times of less than 15 min. The study takes advantage of the inherent extracellular enzymes present in living as opposed to dead, non-enzyme-producing organisms. Sequentially these are harnessed in in vivo reactions with a substrate containing a select organic functional group that is known to be cleaved or hydrolyzed by a certain enzyme. The substrate is tailored so that one of the products can be induced to fluoresce, and by using a conventional spectrofluorimeter the rate at which the fluorescence appears can be recorded. By subjecting the same bacterial sample to a number of different enzyme substrates, a pattern of fluorescence response rates emerges from a 7 by 7 microorganism-substrate matrix. Detection limits ranged from 3.6 X 10(2) to 3.5 X 10(8) cells per ml for the Bacillus globigii-indoxyl acetate and Escherichia coli-diacetylfluorescein pairs, respectively. The specificity and versatility of the method for bacterial determination is demonstrated in probing different bacterial enzymes through their spectrally active metabolic products. PMID- 3089150 TI - Comparison of proteins involved in chondroitin sulfate utilization by three colonic Bacteroides species. AB - Three species of colonic bacteria can ferment the mucopolysaccharide chondroitin sulfate: Bacteroides ovatus, Bacteroides sp. strain 3452A (an unnamed DNA homology group), and B. thetaiotaomicron. Proteins associated with the utilization of chondroitin sulfate by B. thetaiotaomicron have been characterized previously. In this report we compare chondroitin lyases and chondroitin sulfate associated outer membrane polypeptides of B. ovatus and Bacteroides sp. strain 3452A with those of B. thetaiotaomicron. All three species produce two soluble cell-associated chondroitin lyases, chondroitin lyase I and II. Purified enzymes from the three species have similar pH optima, Km values, and molecular weights. However, peptide mapping experiments show that the chondroitin lyases from B. ovatus and Bacteroides sp. strain 3452A are not identical to those of B. thetaiotaomicron. A cloned gene that codes for the chondroitin lyase II from B. thetaiotaomicron hybridized on a Southern blot with DNA from B. ovatus or Bacteroides sp. strain 3452A only when low-stringency conditions were used. Antibody to chondroitin lyase II from B. thetaiotaomicron did not cross-react with chondroitin lyase II from B. ovatus or Bacteroides sp. strain 3452A. Chondroitin lyase activity in all three species was inducible by chondroitin sulfate. B. ovatus and Bacteroides sp. strain 3452A, like B. thetaiotaomicron, have outer membrane polypeptides that appear to be regulated by chondroitin sulfate, but the chondroitin sulfate-associated outer membrane polypeptides differ in molecular weight. Despite these differences, the ability of intact bacteria to utilize chondroitin sulfate, as indicated by growth yields in carbohydrate-limited continuous culture and the rate at which the chondroitin lyases were induced, was the same for all three species. PMID- 3089151 TI - Pilot plant production of rhamnolipid biosurfactant by Pseudomonas aeruginosa. AB - Rhamnolipid biosurfactants were continuously produced with Pseudomonas aeruginosa on the pilot plant scale. Production and downstream processing elaborated on the laboratory scale were adapted to the larger scale. Differences in performance resulting from the scale-up are discussed. A biosurfactant concentration of approximately 2.25 g liter-1 was achieved. The biosurfactant yield on glucose was 77 mg g-1 h-1, and the productivity was 147 mg liter-1 h-1, corresponding to a daily production of 80 g of biosurfactant. The first enrichment step consisted of an adsorption chromatography which was followed by an anion-exchange chromatography. The resulting product was 90% pure, and the overall recovery of active material was above 60% with the downstream processing used. PMID- 3089152 TI - Intergeneric hybrids of Saccharomyces cerevisiae and Zygosaccharomyces fermentati obtained by protoplast fusion. AB - To obtain strains that are able to efficiently produce ethanol from different carbohydrates, mainly cellulose hydrolysates, several species of the genus Candida and a Zygosaccharomyces fermentati strain were examined for their ability to utilize cellobiose and produce ethanol, as well as for their thermotolerance and the possibility of genetic manipulation. Candida obtusa and Zygosaccharomyces fermentati tolerated the maximal temperature for growth, possessed the highest cellobiase activity, and offered the possibility of genetic manipulation, although neither of them proved to be a good producer of ethanol. Intergeneric hybrids of Saccharomyces cerevisiae and Z. fermentati were obtained after protoplast fusion. They were selected as prototrophic strains, after isolation of auxotrophic mutants from Z. fermentati and fusion with an S. cerevisiae strain which was also auxotrophic. The hybrids, which appeared at a frequency of 2 X 10( 7), presented characteristics of both parents, such as resistance to certain drugs and the ability to grow with either cellobiose or lactic acid as the sole carbon source; they were very stable, even under nonselective conditions. These hybrids may have important industrial applications as good fermenting strains. PMID- 3089153 TI - Microbial transformation of quinoline by a Pseudomonas sp. AB - A Pseudomonas sp. isolated from sewage by enrichment culture on quinoline metabolized this substrate by a novel pathway involving 8-hydroxycoumarin. During early growth of the organism on quinoline, 2-hydroxyquinoline accumulated as the intermediate; 8-hydroxycoumarin accumulated as the major metabolite on further incubation. 2,8-Dihydroxyquinoline and 2,3-dihydroxyphenylpropionic acid were identified as the other intermediates. Inhibition of quinoline metabolism by 1 mM sodium arsenite led to the accumulation of pyruvate, whereas inhibition by 5 mM arsenite resulted in the accumulation of 2-hydroxyquinoline as the major metabolite and 2,8-dihydroxyquinoline as the minor metabolite. Coumarin was not utilized as a growth substrate by this bacterium, but quinoline-grown cells converted it to 2-hydroxyphenylpropionic acid, which was not further metabolized. Quinoline, 2-hydroxyquinoline, 8-hydroxycoumarin, and 2,3 dihydroxyphenylpropionic acid were rapidly oxidized by quinoline-adapted cells, whereas 2,8-dihydroxyquinoline was oxidized very slowly. Quinoline catabolism in this Pseudomonas sp. is therefore initiated by hydroxylation(s) of the molecule followed by cleavage of the pyridine ring to yield 8-hydroxycoumarin, which is further metabolized via 2,3-dihydroxyphenylpropionic acid. PMID- 3089154 TI - Contribution of protozoa to lysine synthesis in the in vitro rumen microbial ecosystem. AB - Isotopic tracer experiments were conducted in vitro to determine contribution of protozoa toward the biosynthesis of lysine in the rumen microbial ecosystem. The presence of protozoa in a rumen microbial suspension always increased lysine synthesis from aspartate. Rumen contents from a faunated goat produced a higher amount of lysine than did those from a defaunated one. PMID- 3089155 TI - Identification of epsilon-N-mono-, epsilon-N-di-, and epsilon-N-trimethyllysine by high-performance liquid chromatography. AB - Dansyl derivatives of epsilon-N-mono-, epsilon-N-di-, and epsilon-N trimethyllysine were resolved from other amino acids in proteins by the use of high-performance liquid chromatography. The system was tested with amino acid standard combinations as well as with acid-hydrolyzed proteins known to contain methylated residues. In all cases the methylated lysines were well resolved. PMID- 3089156 TI - Tight coupling of root-associated nitrogen fixation and plant photosynthesis in the salt marsh grass Spartina alterniflora and carbon dioxide enhancement of nitrogenase activity. AB - The coupling of root-associated nitrogen fixation and plant photosynthesis was examined in the salt marsh grass Spartina alterniflora. In both field experiments and hydroponic assay chambers, nitrogen fixation associated with the roots was rapidly enhanced by stimulating plant photosynthesis. A kinetic analysis of acetylene reduction activity (ARA) showed that a five-to sixfold stimulation occurred within 10 to 60 min after the plant leaves were exposed to light or increased CO2 concentrations (with the light held constant). In field experiments, CO2 enrichment increased plant-associated ARA by 27%. Further evidence of the dependence of ARA on plant photosynthate was obtained when activity in excised roots was shown to decrease after young greenhouse plants were placed in the dark. Seasonal variation in the ARA of excised plant roots from field cores appears to be related to the annual cycle of net photosynthesis in S. alterniflora. PMID- 3089157 TI - Enhanced emulsan production in mutants of Acinetobacter calcoaceticus RAG-1 selected for resistance to cetyltrimethylammonium bromide. AB - Mutants of Acinetobacter calcoaceticus RAG-1 that produced elevated levels of the polymeric bioemulsifier emulsan were isolated on the basis of their resistance to the cationic surfactant cetyltrimethylammonium bromide (CTAB). Such mutants showed maximum enhancement in both overall yield and specific productivity of some two- to threefold over that of the wild type. In addition, the effect was also observed in a resting cell system in the presence of chloramphenicol, indicating that the mutation is not simply the result of faster growth. When CTAB tolerant mutants were subjected together with the sensitive parent to the detergent under growing conditions, only the mutants were found to grow. The results suggest that the mutation for CTAB resistance leads to enhanced capsule production. This was confirmed quantitatively by a specific enzyme-linked immunosorbent assay for the cell-bound emulsan minicapsule. PMID- 3089158 TI - Effect of temperature, sodium chloride, and pH on growth of Listeria monocytogenes in cabbage juice. AB - Human illness and death have resulted from the consumption of milk, cheese, and cole slaw contaminated with Listeria monocytogenes. Since the effects of temperature, NaCl, and pH on the growth of the organism in cabbage were unknown, a series of experiments was designed to investigate these factors. Two strains (LCDC 81-861 and Scott A, both serotype 4b) were examined. At 30 degrees C, the viable population of the LCDC 81-861 strain increased in sterile unclarified cabbage juice (CJ) containing 0 to 1.5% NaCl; a decrease in the population of both strains occurred in juice containing greater than or equal to 2% NaCl. At 5 degrees C, the population of the Scott A strain in CJ containing up to 5% NaCl was reduced by about 90% over a 70-day period; the LCDC 81-861 strain was more sensitive to refrigeration but remained viable in CJ containing less than or equal to 3.5% NaCl for 70 days. Growth in CJ at 30 degrees C resulted in a decrease in pH from 5.6 to 4.1 within 8 days. Death of L. monocytogenes occurred at 30 degrees C when the organism was inoculated into sterile CJ adjusted to pH less than or equal to 4.6 with lactic acid. No viable cells were detected after 3 days at pH less than or equal to 4.2. At 5 degrees C, the rate of death at pH less than or equal to 4.8 was slower than at 30 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089159 TI - Red pigment in Bacillus megaterium spores. AB - Bacillus megaterium QM B1551 spores contained a unique red pigment in their membranes that was not found in other species. This red pigment, presumably a carotenoid, was synthesized about the time of dipicolinic acid synthesis during sporulation and was associated with the forespores. A yellow pigment was synthesized during sporulation in rich medium and was found in the mother cell compartment. Although the yellow pigment was also associated with spores, it could be removed by two different extraction procedures without impairing germination; it was absent when sporulation occurred in a minimal medium. Although the yellow pigment of the mother cell appeared to be dispensable, the red pigment may serve a more critical function, such as membrane stabilization. PMID- 3089160 TI - Aflatoxin contamination in soybeans: role of proteinase inhibitors, zinc availability, and seed coat integrity. AB - Soybean trypsin inhibitors are thought to ward off pathogens. Studies with aflatoxigenic strains of Aspergillus flavus and A. parasiticus, frequent soybean contaminants, revealed that trypsin inhibitors do not affect the growth of these fungi and aflatoxin production. Further, the availability of zinc, an essential mineral for aflatoxin synthesis that was thought to explain increased aflatoxin accumulation in cooked compared with raw soybeans, was shown to decrease upon cooking. Seed coat integrity, ensuring limited access and a low moisture content, is responsible for the slow colonization of the seed by A. flavus. PMID- 3089161 TI - Biochemical and immunological characterization of the STA2-encoded extracellular glucoamylase from saccharomyces diastaticus. AB - In Saccharomyces diastaticus each one of three unlinked genes (STA1, STA2, STA3) encodes a glucoamylase (alpha-1,4 glucanglucohydrolase, EC 3.2.1.3) that allows yeast to grow on starch. The enzyme encoded by the STA2 gene (glucoamylase II) has been purified from culture medium to near homogeneity by ethanol precipitation, Trisacryl M DEAE chromatography, and HPLC gel filtration. Glucoamylase II consists of two identical subunits whose average size is 300 kDa. Under denaturing conditions, the native dimeric enzyme readily dissociates to a monomer. Enzymatic deglycosylation of denatured enzyme gives rise to intermediate, partially glycosylated forms and to a 56-kDa completely deglycosylated protein. Glucoamylase releases glucose units by cleaving alpha-1,4 bonds from the nonreducing end of different oligosaccharides, but has only a barely detectable alpha-1,6 hydrolyzing activity. The pH optimum for the purified enzyme was found to be 5.1. The enzyme has a greater affinity for maltohexaose (Km = 0.98 mM, V/Km = 2.39) than for maltotriose (Km = 2.38, V/Km = 0.68) or maltose (Km = 3.20, V/Km = 0.39). Both polyclonal and monoclonal antibodies have been raised against glucoamylase II. The polyclonal antibodies specifically inhibit yeast glucoamylase II activity in a dose-dependent manner, but are found to immunoblot other yeast glycoproteins as well. This oligosaccharide-specific reaction can be competed out by adding excess mannan without affecting glucoamylase reactivity. The cross-reactivity of the polyclonal antibodies with other amylolytic enzymes correlates well with evolutionary distance. Evidence is presented that monoclonal antibodies specific for either carbohydrate or protein epitopes have been obtained. PMID- 3089163 TI - Purification and characterization of a multifunctional calmodulin-dependent protein kinase from canine myocardial cytosol. AB - A calmodulin-dependent protein kinase from canine myocardial cytosol was purified 1150-fold to apparent homogeneity with a 1.5% yield. The purified enzyme had a Mr of 550,000 with a sedimentation coefficient of 16.6 S, and showed a single protein band with a Mr of 55,000 (55K protein), determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme had a specific activity of 1.6 mumol/mg protein/min, and Ka values of 67 nM and 1.1 microM for calmodulin and Ca2+, respectively, using chicken gizzard myosin light chain as substrate. Calmodulin bound to the 55K protein. The purified enzyme had a broad substrate specificity. Endogenous proteins including glycogen synthase, phospholamban, and troponin I from the canine heart were phosphorylated by the enzyme. These results suggest that the purified enzyme works as a multifunctional protein kinase in the Ca2+, calmodulin-dependent cellular functions of the canine myocardium, and that the enzyme resembles enzymes detected in the brain, liver, and skeletal muscle. PMID- 3089162 TI - Effect of insulin on the metabolic distribution of carbons 1, 2, and 3 of pyruvate. AB - It has long been known that the carbons of pyruvate are converted to CO2 at different points in the metabolic process. This report deals with the observation that insulin affects the oxidation of carbons 2 and 3 primarily and has little effect on the oxidation of the carboxyl carbon. Oxidation of different carbons of pyruvate and their incorporation into various metabolic components was studied in isolated rat hepatocytes. Insulin stimulated the 14CO2 production from [2-14C]- and [3-14C]pyruvate and from [U-14C]alanine. However, it had little or no effect on the activity of the pyruvate dehydrogenase complex as measured by the evolution of 14CO2 from [1-14C]pyruvate or [1-14C] alanine. Insulin also stimulated the incorporation of carbons 2 and 3 of pyruvate into protein but had no effect on the incorporation of carbon 1. Incorporation of [1-14C]- and [U 14C]alanine into protein was differentially enhanced by insulin in a manner similar to that of the pyruvate carbons. The fact that insulin stimulates the incorporation of [1-14C]alanine into protein but not [1-14C]pyruvate suggests the possibility of a compartmentation of pyruvate metabolism in the isolated hepatocytes. These studies show that the stimulation of [2-14C]- and [3 14C]pyruvate incorporation into protein involves the stimulatory effect of insulin on the activity of the Krebs cycle which is evident from the fact that insulin did not stimulate the pyruvate carbons to enter protein via alanine but the incorporation via glutamate was increased by about 40%. PMID- 3089164 TI - Purification, properties, and oligomeric structure of glutathione reductase from the cyanobacterium Spirulina maxima. AB - Glutathione reductase [NAD(P)H:GSSG oxidoreductase EC 1.6.4.2] from cyanobacterium Spirulina maxima was purified 1300-fold to homogeneity by a simple three-step procedure involving ammonium sulfate fractionation, ion exchange chromatography on DEAE-cellulose, and affinity chromatography on 2',5'-ADP Sepharose 4B. Optimum pH was 7.0 and enzymatic activity was notably increased when the phosphate ion concentration was increased. The enzyme gave an absorption spectrum that was typical for a flavoprotein in that it had three peaks with maximal absorbance at 271, 370, and 460 nm and a E1%271 of 23.3 Km values were 120 +/- 12 microM and 3.5 +/- 0.9 microM for GSSG and NADPH, respectively. Mixed disulfide of CoA and GSH was also reduced by the enzyme under assay conditions, but the enzyme had a very low affinity (Km 3.3 mM) for this substrate. The enzyme was specific for NADPH. The isoelectric point of the native enzyme at 4 degrees C was 4.35 and the amino acid composition was very similar to that previously reported from other sources. The molecular weight of a subunit under denaturing conditions was 47,000 +/- 1200. Analyses of pure enzyme by a variety of techniques for molecular weight determination revealed that, at pH 7.0, the enzyme existed predominantly as a tetrameric species in equilibrium with a minor dimer fraction. Dissociation into dimers was achieved at alkaline pH (9.5) or in 6 M urea. However, the equilibrium at neutral pH was not altered by NADPH or by disulfide reducing reagents. The Mr and S20,w of the oligomeric enzyme were estimated to be 177,000 +/- 14,000 and 8.49 +/- 0.5; for the dimer, 99,800 +/- 7000 and 5.96 +/- 0.4, respectively. Low concentrations of urea increased the enzymatic activity, but this increase was not due to changes in the proportions of both forms. PMID- 3089165 TI - Chemical modification of rabbit skeletal muscle phosphorylase kinase with phenylglyoxal. AB - Nonactivated phosphorylase kinase from rabbit skeletal muscle is inactivated by treatment with phenylglyoxal. Under mild reaction conditions, a derivative that retains 10-15% of the pH 8.2 catalytic activity is obtained. The kinetics of inactivation profile, differential effects of modification on pH 6.8 and 8.2 catalytic activities, and the insensitiveness of the modified enzyme to activation by ADP reveal that the 10-15% of catalytic activity remaining is very likely due to intrinsic catalytic activity of the derivative rather than to the presence of unmodified enzyme molecules. The kinetic results also suggest that the inactivation is correlatable with the reaction of one molecule of the reagent with the enzyme without any prior binding of phenylglyoxal. The phenylglyoxal modification reduces the autophosphorylation rate of the kinase. Autophosphorylated phosphorylase kinase is inactivated by phenylglyoxal at a much slower rate than the inactivation of nonactivated kinase. Thus, phenylglyoxal modification influences the phosphorylation and vice versa. The modified enzyme can be reactivated by treatment with trypsin or by dissociation using chatropic salts. The activity of the phenylglyoxal-modified enzyme after trypsin digestion or dissociation with LiBr reaches the same level as that of the native enzyme digested with trypsin or treated with LiBr under identical conditions. The results suggest that the effect of modification is overcome by dissociation of the subunits of phosphorylase kinase and that the catalytic site is not modified under conditions when 85% of the pH 8.2 catalytic activity is lost. Among various nucleotides and metal ions tested, only ADP, with or without Mg2+, afforded effective protection against inactivation with phenylglyoxal. At pH 6.8, 1 mM ADP afforded complete protection against inactivation. Experiments with 14C-labeled phenylglyoxal revealed that ADP seemingly protects one residue from modification. This result is in agreement with the kinetic result that the inactivation seemingly is due to reaction of one molecule of the reagent with the enzyme. The results confirm the existence of a high-affinity ADP binding site on nonactivated phosphorylase kinase and suggest the involvement of a functional arginyl residue at or near the ADP binding site in the regulation of of pH 8.2 catalytic activity of the enzyme. PMID- 3089166 TI - Site-directed antisera to the chromophore binding site of phytochrome: characterization and cross-reactivity. AB - The preparation and characterization of antisera to a synthetic undecapeptide which encompasses the chromophore binding site on oat phytochrome are described. By direct enzyme-linked immunosorbent assay, this antiserum recognizes bilin linked peptides in proteolytic digestion mixtures of phytochrome from several plant species including the monocot species, oat and maize, and the dicot species, pea. Competitive enzyme-linked immunosorbent assays have been used to establish the specificity of the site-directed antisera for those peptides homologous with the synthetic undecapeptide which are present in complex mixtures. These results show that the local environment of the phytochromobilin prosthetic group is structurally conserved. PMID- 3089168 TI - Role of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase in the activation process. AB - The large (A) and small (B) subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39) from the cyanobacterium Aphanothece halophytica and from the purple sulfur photosynthetic bacterium Chromatium vinosum (strain D) were separated by sucrose density gradient centrifugation at low ionic strength and alkaline pH (9.3), respectively. It was found that subunit B enhances the extent of activation by CO2 and Mg2+ at equilibrium of the two homologous enzymes consisting of Aphanothece large subunit and its own small subunit (AaBa) and the Chromatium large subunit and its own small subunit (AcBc). The extent of activation induced by saturating amounts of subunit B was larger with AcBc than AaBa, amounting to 3.7- and 1.8-fold of that by each catalytic core alone, respectively. Subunit B stimulated both the extent of activation at equilibrium and catalysis in a parallel and simultaneous manner with respect to the concentration of B in both homologous enzymes. These results suggest that subunit B interacts with both activation and catalytic sites simultaneously. On the other hand, Chromatium subunit B only slightly stimulated the extent of activation in the hybrid enzyme AaBc. The role of subunit B in enhancing the extent of activation at equilibrium can be substituted by the effect exerted by 6 phosphogluconate. Both homologous enzymes AaBa and AcBc showed a faster deactivation rate when the enzyme was activated in the absence of subunit B. The mechanism by which subunit B promotes activation seems to involve its effect on stabilizing the activated enzyme molecule. From studies on the Km for substrate CO2 in the hybrid enzyme AaBc a major involvement of subunit B in influencing Km (CO2) seems unlikely. PMID- 3089167 TI - Bovine liver dihydropyrimidine amidohydrolase: pH dependencies of inactivation by chelators and steady-state kinetic properties. AB - Dihydropyrimidine amidohydrolase (EC 3.5.2.2) catalyzes the reversible hydrolysis of 5,6-dihydropyrimidines to the corresponding beta-ureido acids. Previous work has shown that incubation of this Zn2+ metalloenzyme with 2,6-dipicolinic acid, 8 hydroxyquinoline-5-sulfonic acid, or o-phenanthroline results in inactivation by Zn2+ removal by a reaction pathway involving formation of a ternary enzyme-Zn2+ chelator complex which subsequently dissociates to yield apoenzyme and the Zn2+ chelate (K. P. Brooks, E. A. Jones, B. D. Kim, and E. G. Sander, (1983) Arch. Biochem. Biophys. 226, 469-483). In the present work, the pH dependence of chelator inactivation is studied. The equilibrium constant for formation of the ternary complex is strongly pH dependent and increases with decreasing pH for all three chelators. There is a positive correlation between the value of the equilibrium constant observed for each chelator and the value of its stability constant for formation of Zn2+-chelate. The affinity of the chelators for the enzyme increases in the order 8-hydroxyquinoline-5-sulfonic acid greater than o phenanthroline greater than 2,6-dipicolinic acid. The first-order rate constant for breakdown of the ternary complex to yield apoenzyme and Zn2+-chelate is invariant with pH for a given chelator but is different for each chelator, increasing in the reverse order. The pH dependence of the inactivation shows that two ionizable groups on the enzyme are involved in the inactivation. On the other hand, the steady-state kinetic behavior of the enzyme is well-described by ionization of a single group with a pK of 6.0 in the free enzyme. The basic form of the group is required for catalysis; protonation of the group decreases both Vmax and the apparent affinity for substrate. Conversely, binding of substrate decreases the pK of this group to about 5. L-Dihydroorotic acid is shown to be a competitive inhibitor of dihydropyrimidine amidohydrolase. Binding of L dihydroorotic acid increases the pK of the ionizable group to 6.5. The agreement between the pK in the enzyme-L-dihydroorotic acid complex and the higher pK observed in the pH dependence of inactivation by chelators suggests that the same group is involved in the binding of acid, and chelators. The different effects of substrate and L-dihydroorotic acid on the pK suggest that the binding modes of these two ligands may be different and suggest a structural basis for the mutally exclusive substrate specificities of dihydropyrimidine amidohydrolase and dihydroorotase. PMID- 3089170 TI - [Comparative studies of human natural IFN-alpha, IFN-beta and IFN-gamma with regard to their effects on in vitro immune responses]. AB - Interferon (IFN) is known to affect a variety of immune responses apart from its well-established antiviral and antineoplastic effects. Three human IFN species: IFN-alpha, IFN-beta and IFN-gamma are now clinically available as a result of recent rapid improvements in IFN technology. In view of only the scanty data presently available concerning comparative studies among IFNs with regard to their effects on immune regulation, this report deals comparatively with natural IFN-alpha, IFN-beta and IFN-gamma (all products of Green Cross) with respect to their effects on natural killer cell (NK) activity, chemiluminescence (CL) of fractionated NK cells, lymphoproliferative response induced by PHA, PWM and Staphylococcus aureus COWAN-1 (SAC), and IL-2 production under stimulation with PHA (1:1000). Comparison among IFNs for these immune responses was performed with the same level of antiviral activity (IU). NK activity in the peripheral blood was enhanced in the presence of IFN of all species: to the same extent with IFN alpha and IFN-beta, but significantly less for IFN-gamma as compared with the former. CL of NK cells to IFN was again similar in extent for IFN-alpha and beta, but less for IFN-gamma. Inhibition of PHA and PWM blastogenesis was similar for IFN-alpha and -beta but less for IFN-gamma as shown previously. SAC blastogenesis of both peripheral lymphocytes and tonsillar B cells was enhanced in the presence of IFN-gamma but not in the presence of IFN-alpha or -beta. IL-2 production of peripheral lymphocytes by PHA (1:1000) was dose-relatedly enhanced in the presence of IFN-gamma but not in the presence of IFN-gamma or -beta. PMID- 3089169 TI - Effect of diabetic ketosis on jejunal glutaminase. AB - The intestine is capable of shifting its major fuel source from glutamine in the fed animal to ketone bodies in the fasted animal. Glutaminase (EC 3.5.1.2), the entry enzyme of glutamine oxidation, was examined for its function as a determinant in the utilization of jejunal fuel during diabetes and fasting. Male Sprague-Dawley rats were made ketotic to varied degrees by either fasting or the induction of diabetes with graded doses of streptozotocin (SZ). Specific activity of glutaminase was decreased in the diabetic animals to 64% (p less than 0.05) of controls in the group receiving 110 mg/kg SZ and 82% of controls in the group receiving 65 mg/kg SZ and to 78% (p less than 0.05) of controls in the fasted animals. The activity of glutaminase in the small intestine was negatively correlated to the concentration of beta-hydroxybutyrate in the plasma (r = -0.97, p less than 0.025) and jejunum (r = -0.92, p less than 0.05) for the four groups of animals. Specific activity of glutaminase was decreased in all cell types isolated along the villus-crypt axis of the small intestine from diabetic and fasted rats compared with control rats. The quantity of glutaminase-protein was determined by a dot immunobinding assay using an antibody to purified glutaminase. The activity of glutaminase relative to immunoreactive glutaminase protein was significantly decreased (p less than 0.05) to 53% of control values in the 110 mg/kg SZ group, 77% in the 65 mg/kg SZ group, and 70% in the fasted group. These data indicate that an inactivation of glutaminase-protein may play a role in the ability of the intestine to shift its fuel source from glutamine to ketone bodies during diabetes and fasting. PMID- 3089171 TI - [Anti-cancer treatment with prostaglandin synthetase inhibitor in animal models]. AB - Carcinomas produce elevated quantities of prostaglandins (PGs), particularly the E series, which can play an important role in the suppression of the cellular immune reaction in tumor-bearing individuals. These findings have raised the possibility that PG synthetase inhibitor can restore the immune activity against tumors. The anti-tumor activity of indomethacin, a potent PG synthetase inhibitor, was investigated in mice implanted with colon carcinoma 38, colon carcinoma 26 and Lewis lung carcinoma in a series of model studies for cancer treatment in man. Treatment with indomethacin substantially reduced the levels of PGs, particularly PGE2 in tumor tissue, inhibited the tumor growth, particularly the early stage of cell proliferation, prolonged the survival time, eliminated tumors in the abdominal cavity, and inhibited metastatic tumor recurrence after surgery. Also, the treatment reduced the growth of human gastric and colon carcinomas transplanted into nude mice. Thus, indomethacin might also be effective against human carcinomas. It is postulated that PG synthetase inhibitor may prove to be a good therapeutic tool effective against human cancer when used in combination with chemotherapeutic and other immunotherapeutic drugs as well as with low-dose radiation therapy. PMID- 3089172 TI - [Radiation-induced secondary cancer in patients with uterine carcinoma]. AB - PURPOSE: Radiation-induced cancer has been epidemiologically investigated in occupational or atomic radiation exposure cases. These is also a need to clarify the risk in the case of radiotherapeutical exposure. In this study, therefore, cases of post-irradiated uterine carcinoma which was well cured and followed up over a long term were selected for statistical analysis of radiation-induced cancer in the medical division. MATERIALS AND METHODS: A total of 19,384 patients with uterine carcinoma at seven institutions in Japan were registered on a computer system at the NIRS and were statistically analyzed. Of these, 6,655 patients were treated by surgical procedure alone, 4,310 were given a combined treatment modality of radiation and surgery, 8,419 were treated by radiation alone between 1960 and 1978. Radiation-induced cancer was defined according to the following categories: Secondary cancer was developed within the irradiated field. Time interval was over 5 years after the initial irradiation (leukemia was over 2 years). The cancer had a different histological type to the original one. A total of 43 patients with induced cancer were observed, namely: 14 with rectal cancer, 8 with leukemia, 6 with uterine corpus cancer, 4 with urinary bladder cancer, 3 with osteosarcoma or uterine sarcoma, 2 with sigmoid colon cancer or malignant fibrous histiocytoma, and 1 with ovarian cancer, respectively. RESULTS: Rectal cancer, leukemia and urinary bladder cancer were initially analyzed, because their expected values were easily estimated from the basic data. A total of 8,333 patients (43,418 person-years) from 7 institutions were considered. Their average follow-up period was 10.2 years after treatment. 1) Rectal cancer: Observed value (O) = 14, expected value (E) = 7.83, O/E = 1.79, 95% confidence interval of O/E ratio (CI) = 0.98-2.99, there was no significant difference. 2) Leukemia: O = 8, E = 3.78, O/E = 2.12, CI = 0.91-4.18, no significant difference. 3) Urinary bladder cancer: O = 4, E = 2.23, O/E = 1.79, CI = 0.49-4.55, no significant difference. In other words, no significant difference was observed in the risk of occurrence of secondary cancer among the total number of irradiated patients from the 7 institutions. Since these results, however, were influenced by the accuracy of patient follow-up, the O/E ratio of double cancer in each institution was observed to check the accuracy of the follow-up and 3 institutions were selected for further analysis comprising 2,686 patients (13,588 person-years) in all. Their average follow-up period was 10.1 years.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3089173 TI - [Surgery and adjuvant therapy of gastric cancer]. AB - A remarkable improvement of prognosis has been obtained in surgery for patients with gastric cancer in Japan. This is attributed to the standardization of prophylactic lymphadenectomy and the prescription of adjuvant anticancer chemotherapy. Postoperative long-term cancer chemotherapy (PLCC), available from 1970, using MMC, Tegafur and PSK in addition to curative surgery has prolonged the survival time of patients with serosal and/or secondary lymphatic metastasis. To confirm the efficacy of adjuvant chemotherapy on a wide basis, the Cooperative Study Group of Surgical Adjuvant Chemotherapy for Gastric Cancer was organized in 1975. The first and the second study revealed that postoperative bolus injection of MMC and long-term administration of Tegafur improved the survival rate of patients with stage III and lymphatic with serosal metastasis. The third pilot study showed that immunotherapy using PSK and/or OK-432 with anticancer drugs might be effective for gastric cancer. To promote extensive investigations of a large number of patients, the Japanese Foundation for Multidisciplinary Treatment of Cancer was founded in 1980, and the first study suggested that immunochemotherapy using MMC, Tegafur, PSK and OK-432 is effective for gastric cancer. Efficacy of MMC and Tegafur treatment was obtained in some types, such as female cases, those with undifferentiated adenocarcinoma of Borrmann types II and IV and those given curative resection. It is therefore necessary to seek a proper regimen for each type of patient for the concept of Type-oriented Therapy (TOT). PMID- 3089174 TI - [Intraarterial bolus infusion followed by rapid removal of anticancer agents with hemocarboperfusion under local hyperthermia in advanced hepatic cancer]. AB - Reported herein is a new multidisciplinary treatment modality for unresectable hepatic cancer in which local hyperthermia and intraarterial infusion of bolus anticancer agent are simultaneously undertaken while anticancer agent leaking from the hepatic bed into the general circulation is rapidly removed by charcoal hemoperfusion. Local hyperthermia induced by exposure to 13.56-MHz radiofrequency waves was conducted between one and one and a half hours once or twice a week. During the hyperthermia treatment, a bolus of either 1 mg/kg Mitomycin C or 2 mg/kg Adriamycin was injected into the hepatic artery via a Vascular Access Port, the catheter portion of which had been surgically inserted into the hepatic artery and the reservoir of which had been implanted subcutaneously. In general, a regular dose of 6 mg of Mitomycin C was injected into the Vascular Access Port during the following hyperthermia procedures. In seven of nine patients (78%) treated with this method, a marked reduction in tumor size of more than 50% was observed on computed tomograms. A light to moderate degree of side effects such as leukocytopenia, thrombocytopenia, liver dysfunction or hair loss were noticed after the bolus infusion, but were not so serious as to threaten the patients' lives. PMID- 3089175 TI - [Prognostic characteristics of gallium-positive accumulation in the kidney with renal cell carcinoma by the tomographic whole-body Ga-67-citrate scan]. AB - A frontal tomographic whole-body Ga-67-citrate scan was performed on 67 patients with renal cell carcinoma to clarify the characteristics of gallium uptake by the kidney in relation to the tumor stage and grade, clinical laboratory data and prognosis. Positive gallium uptake by the kidney in 32 patients correlated well with the clinicopathologically higher stage and grade of the tumor and with abnormal values in prognostic indexes in the blood such as erythrocyte sedimentation rate, CRP alpha 2 globulin, ferritin and copper. Gallium accumulation in pulmonary metastatic lesions was found in 13 of 21 patients and all cases with positive uptake by the pulmonary metastatic lesions belonged to the gallium-positive group in the kidney. Kaplan-Meier estimation of survival rate clearly demonstrated bad prognosis in this group. Since the sensitivity of the Ga-67 scan is low but the specificity is high, positive gallium uptake is indicative of an ominous clinical course and shorter survival in patients with renal cell carcinoma. PMID- 3089176 TI - [Surgery and adjuvant therapy of cancer of the large intestine]. AB - The postoperative survival rate after radical surgery for large intestinal cancer shown to be differentiated adenocarcinoma is relatively good. However, the effect of surgical adjuvant therapy on this cancer is considered to be the least promising. 5-FU, FT-207, MMC, ADR and VCR are used for chemotherapy and OK-432, PSK, BCG, levamisole and lentinan are also used as forms of immune therapy. There are no significant differences in the statistics used for comparison with controls as to the effects of these adjuvant therapies. A more intensive regional therapy has therefore been adopted for local recurrence of rectal cancer and liver metastasis of colon cancer considering the form of postoperative cancer recurrence. MMC was injected into the superior rectal artery for rectal cancer and into the portal vein during surgery for colon cancer in the 1st program of research of the Kajitani group. However, the efficacy of these procedures was not proved. Although immune therapy with OK-432 has also been subsequently added in the second research program, no efficacy was apparent. Taylor and Birmingham have reported that liver metastasis was remarkably decreased by continuous infusion of 5-FU through the portal vein. There is also a report by GITSG in the USA that a reduction of local recurrence was obtained by combination of 5-FU and Me-CCNU with irradiation treatment after surgery for rectal cancer. PMID- 3089177 TI - [The concentration in the tissue and antitumor effect of anticancer drug- assessment of breast cancer with UFT or FT-207]. AB - The correlation between intralesional 5-FU concentrations and the extent of antitumor effect with particular attention to histopathology was assessed in 30 patients with breast cancer. Therapy consisted of either UFT or FT-207 given preoperatively. Although the UFT-treated group showed a significantly higher intratumoral concentration of 5-FU, there was no intergroup difference in 5-FU levels in normal tissue. In addition, this greater concentration of intratumoral drug had no significant effect on therapeutic response; for both UFT and FT-207 treated groups, the histologic interpretation was rated as grade IIa. Regardless of which drug was used, when tumors were stratified according to histologic type, papillotubular carcinomas revealed the greatest tissue 5-FU levels. However the greatest histologic antitumoral responses were seen in scirrhous carcinomas; hence no correlation was seen here either. The results suggest that attainment of a high intratumoral 5-FU concentration is not reflected in a better histologic tumor response in patients receiving the above drug regimens. PMID- 3089178 TI - [A case of multiple liver metastases from sigmoid carcinoma treated successfully with arterial infusion chemotherapy]. AB - A 63-year-old female, who had undergone sigmoidectomy for sigmoid carcinoma one year before, was admitted for multiple liver metastases. A urokinase-immobilized catheter was introduced into the proper hepatic artery via the gastroepiploic artery operatively. A daily arterial infusion of 5-FU (250 mg) was combined with a weekly arterial infusion of adriamycin (30 mg) or MMC (10 mg). After discharge, 5-FU (200 mg/day) was given orally and MMC (10 mg) was infused intraarterially every other week at an outpatient clinic. ADR or MMC was infused with angiotensin II, known to increase arterial blood supply to a malignant lesion. Ultrasonography demonstrated 35 to 50% reduction in tumor diameter. The density of metastases seen in computerized tomography became low indicating tumor necrosis. Plasma CEA level, which had initially been as high as 864 ng/ml, decreased rapidly and has remained within normal limits up to the present time. Arterial infusion chemotherapy using 5-FU, ADR or MMC in combination with angiotensin II seems to be effective in the treatment of multiple hepatic metastases from colorectal carcinoma. PMID- 3089179 TI - Hepatitis B virus infection in multitransfused haemophiliacs. AB - A longitudinal study of 44 haemophilic children, all in a treatment programme with factor concentrates, was undertaken to evaluate the occurrence, characteristics, and evolution of hepatitis B virus (HBV) infection. Twenty four children (55%) (group I) showed signs of HBV infection, while 20 (45%) (group II) did not. Age at onset of treatment, number of infusions, and total amount of concentrate received did not show significant differences between the two groups. In group I only four children (16%) had symptomatic acute hepatitis. Chronic liver disease was present in nine patients (38% of infected children). The early age of infection would seem to be an important factor for predicting chronic evolution. Evidence of delta infection in three children with severe liver disease seemed to confirm the high pathogenicity of this agent. Because of the risks associated with chronic HBV infection a careful follow up of patients positive for hepatitis B surface antigen is mandatory. PMID- 3089181 TI - [Bulbourethral diverticuli]. PMID- 3089180 TI - Cell culture studies on neurofibromatosis (von Recklinghausen's disease). IV. Collagen synthesis. AB - Comparative measurements of collagen synthesis as a portion of total protein synthesis were performed with fragments of peripheral neurofibromas, of skin adjacent to the tumors, and of unaffected skin from patients with neurofibromatosis (NF). No significant difference was found among these various samples. Collagen synthesis was also measured in cell cultures derived from peripheral neurofibromas of eight NF patients and from skin of ten healthy donors. No differences observed in the following respective parameters: dependence on the concentration of fetal calf serum; dependence on cell population density; portion of synthesized collagens in the culture medium and the cell layer. The ratios of synthesized collagen types III to type I, determined in five pairs of NF and control strains, vary within the same range. PMID- 3089182 TI - Duodenojejunostomy for the pancreaticobiliary complications of duodenal diverticulum. PMID- 3089184 TI - Concentration of Plasmodium vivax-infected erythrocytes. PMID- 3089183 TI - Effects of infection on oxygen consumption and core temperature in experimental thermal injury. AB - Oxygen consumption (VO2) and colonic temperature (Tc) were measured in groups of rats before and after 30% total body surface, full thickness burns. Some wounds were seeded with Pseudomonas aeruginosa or Staphylococcus epidermidis, and some seeded wounds were treated with Sulfamylon or Silvadene. Three groups became bacteremic (B) during the 2-3 week period of observation. At an ambient temperature (Ta) of 32 C, VO2 of the B group rose from 0.83 +/- 0.01 to 1.20 +/- 0.01 ml/hr/g (mean +/- S.E., p less than 0.001) versus 0.81 +/- 0.01 to 0.99 +/- 0.02 for nine nonbacteremic (NB) groups (p less than 0.001). Tc increased only in the B groups--from 36.8 +/- 0.1 to 37.7 +/- 0.1 C (p less than 0.001). In the second or third week postinjury, VO2 of the NB rats was reduced when Ta was increased to 34 C; Tc followed changes in Ta. Sulfamylon lowered VO2 of P. aeruginosa seeded, NB rats. The metabolic cost of wound contamination appeared to vary with bacterial strain. The metabolic effects of infection appear to be a continuum, beginning with a modest rise in VO2 and progressing to greater increases in VO2 and Tc with wound invasion and systemic infection. PMID- 3089185 TI - The role of human water contact patterns in the transmission of schistosomiasis in an informal settlement near a major industrial area. AB - Human contact with schistosome-infested water was studied in a rapidly growing community near an industrial area: water-contact was observed and categorized; interviews concerning water usage were conducted and schoolchildren and adult women were tested for schistosome infections. Results indicated that swimming amongst certain young people was an important contact activity in summer. To a lesser extent the washing of clothes and blankets was found to be an activity of importance, providing a focus for the social gathering of women and young children in contact with the water throughout the year. One of the aims of the study was to develop cost-effective methods for use in this and other endemic areas to provide guidelines for control programmes. A comparison was made between methods of assessing exposure to the infection in their ability to predict the prevalence of Schistosoma haematobium and S. mansoni across age-sex classes of the human host; an exposure index which included an assessment of body surface area was found to be preferable to one based on duration of contact only. The differing relationships between exposure to infested water and prevalence of the two schistosome species were in accordance with reports from other areas, thus supporting the choice of minimum requirements for a survey prior to control. PMID- 3089186 TI - High-density lipoprotein and glycosylated hemoglobin in nondiabetic individuals. AB - We investigated associations of high-density-lipoprotein (HDL) cholesterol, apolipoprotein A-I, and triglyceride levels with hemoglobin A1 (HbA1) and insulin levels in nondiabetic subjects (137 women and 111 men). In women, HDL cholesterol, apolipoprotein A-I, and log-triglyceride values were significantly correlated with those of HbA1 and log-fasting insulin. These univariate associations persisted when age and Quetelet's index were included as covariates in multiple regression analyses. Conversely, univariate associations of HDL cholesterol and log-triglyceride levels with Quetelet's index were diminished by the addition of insulin values to multivariate models. Insulin levels and Quetelet's index were highly correlated. Although there were weaker associations in men, apolipoprotein A-I and HbA1 values were inversely related. These data suggest that HDL cholesterol and apolipoprotein A-I levels are closely linked to glucose metabolism in nondiabetic individuals. PMID- 3089187 TI - Immobilization hypercalcemia associated with Landry-Guillain-Barre syndrome. Successful therapy with combined calcitonin and etidronate. AB - Two patients with immobilization hypercalcemia associated with Landry-Guillain Barre syndrome had marked hypercalciuria (890 and 1136 mg/d [22.2 and 28.3 mmol/d]) and radiologic evidence of generalized osteopenia. Parathyroid hormone levels were either low or normal by C-terminal radioimmunoassay. Subtotal parathyroidectomy was performed in the one patient, with no improvement in serum or urinary calcium levels. A bone biopsy specimen revealed decreased cellular activity in the first patient and increased bone resorption in the second patient. Treatment with intravenous saline, furosemide, oral phosphate supplementation, mithramycin, and calcitonin alone was ineffective in lowering serum or urinary calcium levels. However, when subcutaneous calcitonin combined with oral etidronate disodium was used, a reduction in the serum calcium level was observed within two days of therapy. Within one week of the start of this combined therapy, the calcium level returned to normal and urinary calcium excretion was substantially reduced. PMID- 3089188 TI - Influence of very low doses of ionizing radiation on Synechococcus lividus metabolism during the initial growth phase. AB - Previous results from this laboratory have shown that very low chronic doses of gamma radiation can stimulate proliferation of the Cyanobacterium Synechococcus lividus. This modification of cell proliferation occurred during the first doubling. In this paper, we have compared the metabolism of cells cultivated in a normal environment or under chronic irradiation. Incubation of the cells in a new medium induced a high superoxide dismutase (EC 1.15.1.1, SOD) activity at the 18th hour and a degradation of phycocyanin, thus demonstrating that cells were submitted to a photooxidative stress. This increase in superoxide dismutase activity was followed by concomitant peaks of glutathione reductase (EC 1.6.4.2, GR) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6P-DH) at the 24th hour. Irradiated cultures at a dose of 53.5 mGray/year show an earlier and higher peak of SOD, GR, and G6P-DH. In a second stage, cultures showed an earlier onset of photosynthesis under irradiation, as evidenced by an increase in pigment content and an enhancement of glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.13, GAP DH). These results show that the radiostimulation is related to the activation of enzymes protecting against peroxides that were induced under oxidative circumstances and to the activation of a glucose catabolism via the oxidative pentose phosphate pathway. PMID- 3089189 TI - [Prevention of colienterotoxemia in swine]. PMID- 3089190 TI - [Cardiorespiratory effects of ketamine hydrochloride in guinea pigs (Cavia cobaya)]. PMID- 3089191 TI - A modified method of fine-granular cationic iron colloid preparation: its use in light and electron microscopic detection of anionic sites in the rat kidney glomerulus and certain other tissues. AB - Ferric chloride, when boiled with hydrazine hydrate and cacodylic acid, is converted into a fine cationic iron (ferric hydroxide) colloid which consists of 0.5-1.5 nm electron-dense granules, and gives a distinct Prussian blue reaction. This colloid allows light and electron microscopic detection of ionized anionic sites in tissues at a wide pH range of 0.8-7.6. It is smaller in size and more stable, and assures longer and greater staining of tissues, especially at low pH levels, than the iron colloid prepared with sodium or ammonium cacodylate by Seno and his associates (1983, 1984, 1985). Some light and electron micrographs of the rat kidney, spleen and other organs stained with our colloid are presented as examples. These micrographs confirm that the glomerular podocyte end-foot surface facing the Bowman's capsular space is strongly negative-charged. They also show that almost all lymphoid cells around the arteries in the splenic white pulp and thymic cortex contain strongly negative-charged nuclei and that the distal convoluted and collecting urinary tubules are more negative-charged than the proximal convoluted tubules. PMID- 3089192 TI - Lectin histochemistry of papillary and follicular carcinoma of the thyroid gland. AB - The lectin-binding properties of human follicular and papillary carcinoma were studied histochemically and compared with lectin binding to normal or goitrous thyroid tissue. Well-differentiated minimally invasive follicular carcinoma showed a lectin-binding pattern essentially identical to those of the normal thyroid gland and benign adenomatous lesions. Overtly invasive follicular carcinoma showed focal reactivity with some lectins that were nonreactive with normal follicular thyroid cells (Solanum tuberosum and soybean in three of three cases; Ulex europaeus in two of three cases; and Dolichos biflorus, Laburnum alpinum, and peanut in one of three cases). In papillary carcinomas, the cells lining the papillary structures reacted focally with some lectins that did not bind to normal thyroid cells (S tuberosum and U europeaus in seven of seven cases; Helix pomatia, Helix aspersa, and soybean in four of seven cases; and peanut, Griffonia simplicifolia, D biflorus, and Vicia villosa in one of seven cases). All these lectins, as well as those reacting with normal thyroid cells, reacted more strongly with cells of papillary structures than with those forming solid nests and follicles. Despite these lectin-defined differences in the composition of glycoconjugates of benign and malignant thyroid cells, the inconsistent and focal nature of the changes precludes the use of lectins in diagnostic histopathology. PMID- 3089193 TI - S-aryl(tetramethyl)isothiouronium salts as possible antimicrobial agents, I. PMID- 3089194 TI - Respiratory response to inversion in normal subjects. AB - To evaluate the respiratory response to inversion, 20 young male athletes were suspended by their ankles in a vertical head-down position, while being monitored with ear oximetry and end-tidal CO2 nasal cannula. There was a decrease in O2 saturation (p less than 0.01), increase in end-tidal CO2 (p less than 0.01), and a decrease in respiratory rate (p less than 0.02). Spirometry was done in seven of these subjects, revealing decreases in forced vital capacity (5.7% +/- 2.0%), FEV1 (10.9% +/- 4.0%), FEF25-75 (13.3% +/- 7.4%), and peak expiratory flow rate (20.1% +/- 4.4%). Caution is advised in the use of inversion devices in patients with compromised cardiopulmonary service. PMID- 3089195 TI - Prophylaxis against radiation injury. The use of elemental diet prior to and during radiotherapy for invasive bladder cancer and in early postoperative feeding following radical cystectomy and ileal conduit. AB - Previous studies done in animals have shown that significant prophylaxis against radiation injury could be afforded by feeding an elemental diet (ED) for three days before and during radiation. In the present study 20 patients were fed an ED for three days before and for the four days during radiotherapy (five fractions of 400 rad [4 Gy] each) prior to radical cystectomy and ileal conduit for invasive bladder cancer; ED feeding was recommenced 24 hours postoperatively via a feeding jejunostomy. The ED-fed patients exhibited positive nitrogen balance preoperatively and had an early return to positive nitrogen balance postoperatively (3.60 +/- 0.32 days). There was also prompt return of bowel sounds (3.00 +/- 0.32 days). Histologically and ultrastructurally, biopsy specimens of the ileal mucosa showed normal morphologic findings, with maintenance of normal levels of enzyme activity in the brush border. Severe or bloody diarrhea was absent in these patients. These data suggest that ED feeding provides prophylaxis against the acute phase of radiation injury in patients undergoing high-dose, short-course radiotherapy for invasive bladder cancer and that it is a safe and feasible means of postoperative nutritional support, even in the presence of a fresh bowel anastomosis. PMID- 3089196 TI - Laser welding of venotomies. AB - We investigated the histologic and biochemical effects of carbon dioxide and neodymium (Nd)-YAG laser welding on the healing of venotomies. Ten canine femoral venotomies 2 cm in length were approximated and welded with 10 600-nm wavelength, 1-W power over 20 to 25 s for CO2 laser, and 1060-nm wavelength, 1-W power over 30 to 40 s for Nd-YAG laser. On removal at one to three weeks, all veins (4/4 welded by CO2 and 6/6 by Nd-YAG) were patent without hematomas. Histologic and biochemical analyses of the venous tissues demonstrated active healing at the venotomy sites. We conclude that the CO2 and Nd-YAG lasers can be used successfully to weld venotomies and may provide an alternative to conventional suture techniques for repair of vascular lesions. PMID- 3089197 TI - William A. Altemeier lecture. Nutrition and infection. New perspectives for an old problem. AB - Dietary variables have an important influence on immunologic responses, resistance to infection, and survival. Injury and infection can markedly alter dietary requirements and the diet can markedly influence the body's response to injury and/or infection. Experiments are described that show that diets following burn injury required more energy intake, more protein (22% vs 15%), and less fat (10% vs 50%) for optimal support. Oral administration (vs intravenous) improved outcome, especially when given immediately after the burn, which prevented the hypermetabolic response. Crystalline amino acids in the enteral diet had an adverse effect compared with intact protein. The type of lipid in the diet after burn injury strongly influenced immunologic and inflammatory responses, with eicosapentaenoic acid being beneficial and linoleic acid being harmful. Dietary manipulation in surgical disease, especially infection, will have an increasingly important role in outcome as these complex interactions are dissected and understood. PMID- 3089199 TI - What is the best treatment for Reye's syndrome? PMID- 3089198 TI - Influenza virus strains with a fusion threshold of pH 5.5 or lower are inhibited by amantadine. Brief report. AB - Nineteen influenza virus strains were examined for susceptibility to amantadine HCl (AMT) and for pH-thresholds of haemagglutinin-induced haemolysis. Whereas pH thresholds below 5.5 were not seen in AMT-resistant strains, AMT-sensitive strains showed pH-thresholds either below or above 5.5. PMID- 3089200 TI - Pathologic findings in fetal GM1 gangliosidosis. AB - A 24-week fetus with GM1 gangliosidosis (type 1) was studied using biochemical and histopathologic methods. Foam cells in viscera and placenta demonstrated widespread accumulation of a lipidlike material. By microscopy, central nervous system storage appeared confined to the retina and dorsal root ganglia, but the brain ganglioside content was measurably elevated compared with that of age matched controls. These data, along with those of others, imply that, if the observed pathologic findings are irreversible, any attempts at intrauterine therapy must commence prior to the middle of the second trimester. PMID- 3089201 TI - Predicting posttraumatic epilepsy in penetrating head injury. AB - Using data derived from a 15-year follow-up study of 520 veterans surviving penetrating brain wounds received in the Vietnam war, we have developed a predictive formula and tables for posttraumatic epilepsy based on time elapsed postinjury and presence of specific clinical and computed tomographic scan risk factors. Such patients remain at some increased risk for epilepsy even ten to 15 years postinjury, although most can be 95% certain of avoiding epilepsy if they have been seizure free for three years posttrauma. Epilepsy onset latency was independent of any risk factors identified. PMID- 3089202 TI - Clobazam for refractory focal epilepsy. A controlled trial. AB - The effect of 1,5-benzodiazepine clobazam was assessed in a double-blind add-on trial in 20 patients with chronic complex partial seizures uncontrolled by maximally tolerable daily dosage of standard antiepileptic drug therapy. The number of seizures was lower during the three months of active treatment. At the end of the third month, eight (40%) of the patients had a seizure reduction by more than 75%, including four patients (20%) who had complete control. Tolerance to the antiepileptic effect of clobazam was noted in 56% of the patients, and mild transient sedation occurred in 40% of the patients. Despite these drawbacks, clobazam is an effective add-on drug for individual patients with refractory focal epilepsy. PMID- 3089203 TI - Proximal motor neuropathy, dermato-endocrine syndrome, and IgG kappa paraproteinemia. AB - The association of monoclonal paraproteinemia, neuropathy, and dermato-endocrine disturbances is well recognized in Japan, and it also occurs in white patients. Neuropathy in such patients is classically distal and sensorimotor, and the paraprotein almost always contains lambda light chains. A 58-year-old white man presented with severe progressive proximal motor neuropathy, dermato-endocrine changes, and an IgG kappa paraprotein. Over a 2 1/2-year period, treatment with melphalan and prednisolone produced improvement in the neuropathy and resolution of dermato-endocrine features with a corresponding decline in the serum paraprotein concentration. Subsequent reappearance of the paraprotein, despite treatment, was associated with clinical relapse. PMID- 3089204 TI - Association of lupuslike anticoagulant and nonvasculitic cerebral infarction. AB - The lupus anticoagulant has been theoretically linked with cerebrovascular dysfunction. All previously described patients, however, have had other concomitant conditions known to predispose them to stroke. The patient described herein demonstrates the association of a lupuslike anticoagulant with thrombotic vascular occlusion in the central nervous system in the absence of other causes of vasculopathy. PMID- 3089206 TI - Hepatitis. PMID- 3089205 TI - A proposed structure of chondroitin 6-sulfate proteoglycan of human normal and adjacent atherosclerotic plaque. AB - Chondroitin sulfate proteoglycan monomers were prepared from intima media minces of grossly normal human aorta and adjacent fatty fibrous atherosclerotic plaques. Glycosaminoglycan chains prepared from monomer from normal aorta displayed a normal distribution profile on Ultrogel ACA 54 with a Kav of 0.48, whereas those of atherosclerotic aorta displayed a bimodal distribution (major peak, Kav 0.35; minor peak, Kav 0.70). The Mr of glycosaminoglycans from normal aorta was estimated to be 1.5 X 10(4). For atherosclerotic aorta, the majority of chains were 2.0 X 10(4) while the smaller population was 1.2 X 10(4). All glycosaminoglycans were identified as chondroitin sulfate sulfated at the C-6 position. The amino acid compositions of both core proteins were similar with Mr of about 1.6 X 10(5). After beta-elimination in the presence of sodium borohydride prior to acid hydrolysis, chondroitin sulfate proteoglycan from normal aorta had reductions in serine from 109 to 68 and in threonine from 117 to 55. For the monomer from atherosclerotic plaque, reductions in serine and threonine, respectively, were from 103 to 81 and from 107 to 77 residues per 1000. The results suggested fewer chondroitin sulfate chains and oligosaccharides on the core protein in the proteoglycan of atherosclerotic plaque. Compared to normal aorta, substituted serines and threonines in the proteoglycan of atherosclerotic plaque were about half, respectively, 38% vs 21% for serine, 53% vs 28% for threonine. It is estimated that in atherosclerotic plaque there are fewer, but longer, chondroitin sulfate chains per core protein, translating into a smaller overall monomer size in atherosclerotic plaque. PMID- 3089207 TI - Extension of the Commonwealth standard of absorbed dose from cobalt-60 energy to 25 MV. PMID- 3089208 TI - Anergy and the severely ill surgical patient. AB - Delayed hypersensitivity skin test reaction was evaluated using Multitest CMI, an implement which provides seven standardized antigens in a single application. Eighty-two patients requiring Total Parenteral Nutrition for a variety of conditions were studied. The incidence of anergy was 65%. Seven anergic patients died, but there were no deaths in the reactive group, this difference being significant (P = 0.04). There was a significant association of anergy with carcinoma (P = 0.007) and anergic patients with carcinoma had a significantly greater risk of dying than reactive patients without carcinoma (P = 0.038). Anergic patients also had significantly lower nutritional parameters of serum albumin (P = 0.04), transferrin (P less than 0.001), absolute lymphocyte count (P = 0.009) and mid-arm muscle circumference (P = 0.02) compared to the reactive group. PMID- 3089209 TI - Gastric and intestinal bleeding in multiple neurofibromatosis with cardiomyopathy. AB - A case of multiple neurofibromatosis is described with histologically divergent lesions in the jejunum, stomach and colon presenting with bleeding and complicated by idiopathic hypertrophic subaortic stenosis. An aggressive surgical approach to gastro-intestinal bleeding in multiple neurofibromatosis is recommended. PMID- 3089211 TI - Double bladder (report of two unusual cases). PMID- 3089210 TI - Clinical experience with systemic vasodilator therapy in the newborn infant. AB - Newborn infants with impaired myocardial performance may not respond to inotropic drugs and volume loading. Vasodilator therapy was tried in 10 such patients and in most there was improvement in peripheral perfusion, blood pH, arterial oxygenation, blood pressure and urine output. No complications of these drugs were detected. Vasodilator therapy has a role in the management of the acutely sick newborn infant with clinical signs of low cardiac output. PMID- 3089212 TI - Beyond language--speculations on the prefrontal cortex and schizophrenia. AB - Changes to the structural complexity of the spoken language of schizophrenic patients have been demonstrated in three recent studies. The speculation is offered that these changes could result from dorsolateral prefrontal cortical dysfunction. Impairment of the executive functions of this part of the brain could theoretically explain both the varied symptomatology of schizophrenia and its unique pattern of ages of onset. PMID- 3089213 TI - Genetic variation for superoxide dismutase level in Drosophila melanogaster. AB - We have studied genetic variation for levels of activity of the enzyme superoxide dismutase (SOD) in Drosophila melanogaster. We have constructed 34 lines homozygous for a given second and a given third chromosome derived from eight original lines; all lines were homozygous for the "fast" (F) allele of Sod. The variation in the relative levels of SOD CRM ranges from 1 to 1.6. The second chromosomes modify the SOD level, even though the structural Sod locus is in the third chromosome, and the specific effect of a given second chromosome depends on the particular third chromosome with which it is combined. This indicates that the variation in SOD content is controlled by polygenic modifiers present in the second (and in the third) chromosome. In addition to these trans-acting modifiers, we have isolated a cis-acting element (SodCA1) that reduces SOD CRM levels to 3.5% of a typical F/F homozygote. SodCA1 is either a mutation in a regulatory site closely linked to the structural locus or a change in the coding sequence affecting the rate of degradation of the enzyme. PMID- 3089214 TI - Relationship between alpha-glycerophosphate dehydrogenase activity and metabolic rate during flight in Drosophila melanogaster. AB - Measurements of wing-beat frequency (WBF) have been used to characterize flight muscle metabolic rate in Drosophila melanogaster during tethered flight. Progeny of crosses between 17 X-chromosome substitution lines and three null-activity stocks have been studied in order to determine the effect on flight metabolism of sharply reduced activity of alpha-glycerophosphate dehydrogenase (alpha GPDH). It was found that flies with an approximate 50% reduction in alpha GPDH activity have a metabolic rate that is, in most cases, indistinguishable from that of wild type flies and, in the most extreme cases, reduced by only 4%. These results demonstrate that alpha Gpdh is not a "major gene" for flight metabolism, in the quantitative genetic sense of the term. These results are in agreement with the Kacser and Burns (1973, 1979, 1981) theory of flux, which postulates that the activity of an enzyme embedded in a multienzyme pathway can sometimes vary from wild-type to very low levels (perhaps 5-10% wild type) with no significant effect on flux through the total pathway. PMID- 3089215 TI - A sensitive immunoblotting technique to identify thyroxin-binding globulin protein heterogeneity after isoelectric focusing. AB - An enzyme-linked immunoblotting technique is described to detect thyroxin-binding globulin (TBG) variation in human plasma samples after isoelectric focusing in thin-layer polyacrylamide gels followed by transfer to a nitrocellulose membrane. The technique is used to demonstrate the polymorphic variation in thyroxin binding globulin present in populations of African and Mongoloid origin and has enabled the detection of a new TBG variant in Eskimos. This technique eliminates the use of radioactive material and related expensive equipment. The technique is specific, sensitive, and reliable for the routine detection of genetic and epigenetic variation in thyroxin-binding globulin. PMID- 3089216 TI - Analysis of Aldoxn alleles isolated from natural populations of Drosophila melanogaster. AB - Aldox "null" alleles which were isolated from natural populations in Great Britain and North Carolina were analyzed for complementation. No complementation was observed between any combinations of "null" alleles for aldehyde oxidase (AO) specific activity in late third-instar larvae and newly emerged adults. AO immunologically cross-reacting material (AO-CRM) was quantitated in all homozygous stocks at both developmental stages as well as all allelic combinations in newly emerged adults. When the adult organism contains only Aldoxn alleles, the polypeptides are not immunologically recognizable or may be rapidly degraded. Larvae and adults have different abilities to degrade mutationally altered enzymatically inactive AO polypeptide or synthesize them differentially. This is indicated by easily measurable AO-CRM levels in late third-instar larvae of Aldoxn homozygotes, while newly emerged adult Aldoxn homozygotes have very little, if any, AO-CRM. Newly emerged adult heterozygotes of Aldoxn/Aldox+ do have increased AO-CRM, indicating that the Aldoxn alleles can code for a polypeptide which can be "rescued" if Aldox+ gene product is present. Heterozygotes containing an Aldox+ allele with a deficiency for the Aldox region produce 74.2% of the AO-CRM found in Aldox+ homozygotes. This may indicate the presence of trans-acting factors which serve to activate gene expression in a system in which each gene copy is not maximally expressed. PMID- 3089217 TI - X-linked mutations that give rise to overproduction of glucose-6-phosphate dehydrogenase in Drosophila melanogaster. AB - Two X-linked mutations that give rise to overproduction of glucose-6-phosphate dehydrogenase (G6PD) were found among the progenies of isogenic strains which had been subjected to selection for high G6PD activity. Mapping of the high-activity factor in these mutants was carried out using car ZwB sw males of low G6PD activity. As a result, the factor mapped 0.02-0.04 unit to the left of the Zw locus. The amount of the G6PD gene was also quantitated utilizing a cloned G6PD gene as a probe, but no significant difference was found between the mutants and low-G6PD activity flies which shared the same X, second, and third chromosomes with the mutants. These findings are consistent with our notion that the mutations might be regulatory mutations, possibly resulting from the insertion of a novel class of transposable genetic elements. PMID- 3089218 TI - Potent and prolonged melanotropic activities of the alpha-MSH fragment analog, Ac [Nle4,D-Phe7]-alpha-MSH4-9-NH2. AB - Ac-[Nle4, D-Phe7]-alpha-MSH4-9-NH2 and Ac-[Nle4]-alpha-MSH4-9-NH2, fragment analogs of the tridecapeptide, alpha-melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin), were synthesized. The potency and prolonged activity of the analogs were compared to alpha-MSH in several melanotropin bioassays. The D-Phe containing hexapeptide was 10 times more active than alpha-MSH in stimulating melanoma tyrosinase activity. This analog was also 10-fold more potent than alpha MSH in the lizard skin bioassay and about 10-fold less active in the frog skin bioassay. The melanotropic activity of Ac-[Nle4, D-Phe7]-alpha-MSH4-9-NH2 was considerably prolonged compared to alpha-MSH in each of the bioassays. These results demonstrate that the structural requirements for superpotency and prolonged activity of [Nle4, D-Phe7]-substituted analogs reside within this hexapeptide sequence. PMID- 3089219 TI - Lapachol inhibition of DT-diaphorase (NAD(P)H:quinone dehydrogenase). AB - Lapachol has been found to be a potent inhibitor of the enzyme DT-Diaphorase. Inhibition is competitive versus NADH, Ki = 0.15 microM. Lapachol was not a good substrate for cytochrome P450 reductase, thus inhibition of DT-Diaphorase should not promote its metabolism via radical generating pathways. DT-Diaphorase has been used to test a lapachol affinity chromatography column designed for purification of another coumarin anticoagulant and lapachol sensitive enzyme, vitamin K epoxide reductase. PMID- 3089220 TI - alpha-Difluoromethylornithine does not bind to ornithine decarboxylase-antizyme complex. AB - alpha-Difluoromethylornithine (DFMO) has been widely used for determining the amounts of ornithine decarboxylase (ODC) in cells. However, we have now found that DFMO does not react with ODC-antizyme complex, indicating that the amounts of radioactive DFMO bound to the protein may not reflect the amounts of ODC in crude tissue extracts. PMID- 3089221 TI - Alterations in deoxynucleoside triphosphate metabolism in DNA damaged cells: identification and consequences of poly(ADP-ribose) polymerase dependent and independent processes. AB - Treatment of L1210 cells with increasing concentrations of MNNG produces heterogeneous perturbations of cellular deoxynucleoside triphosphate pools, with the magnitude and direction of the shift depending on the deoxynucleotide and on the concentration and time of exposure of the DNA damaging agent. 5 microM MNNG stimulated an increase in dATP, dCTP and dTTP but dGTP pools remained constant. These increases were not affected by 3-aminobenzamide, indicating that the pool size increases were produced by poly(ADP-ribose) polymerase independent reactions. 30 microM MNNG caused a time dependent decrease in dATP, dGTP, dTTP and dCTP. The dGTP pool was most drastically affected, becoming totally depleted within 3 hours. The fall in all 4 dNTP pools was substantially prevented by 3 aminobenzamide, suggesting that the decrease in dNTPs following DNA damage is mediated by a poly(ADP-ribose) polymerase dependent reaction. Severe depression of dGTP pools consequent to NAD and ATP depletion may provide a metabolic pathway for rapidly stopping DNA synthesis as a consequence of DNA damage and the activation of poly(ADP-ribose) polymerase. PMID- 3089222 TI - Studies on the human blood group P system: an existence of UDP Gal:lactosylceramide alpha 1----4 galactosyltransferase in the small p type cells. AB - Human red blood cells and other tissues with the rare small p type lack all P antigens, and are assumed to be missing key glycosyltransferases in the synthetic pathway of P antigens. Galactosyltransferase activities of the P1 and small p cell extracts were measured using lactosylceramide and GlcNAc as galactose acceptors. The two transferase activities of the small p lymphoblastoid cell extract were comparable to that of the P1 cell extract. The anomeric configuration of the galactosylated lactosylceramide was established by digestion with alpha- and beta-galactosidases, by identification of methylated products, and by staining with the monoclonal antibody against globotriaosyl ceramide (Pk antigen). The results indicate that UDP-Gal:LacCer alpha 1----4 Gal transferase, which produces the Pk antigen from the precursor LacCer, exists in the small p cells. However, intact small p cells could not produce the Pk antigen, and, instead, LacCer was accumulated in the cells. The Pk enzyme appears to be not functional in the small p cells in vivo. PMID- 3089223 TI - Biosynthesis of thiamin. Precursor of C-5, C-6, and hydroxymethyl carbon atoms of the pyrimidine moiety in a eucaryote. AB - We studied the incorporation of radioactive glucose into the pyrimidine moiety of thiamin in the eucaryote Candida utilis. Three carbons of glucose were incorporated into the pyrimidine, and the C-2 of glucose into the C-6 of the pyrimidine. We concluded that the C-5, -6, and hydroxymethyl carbon atoms of the pyrimidine in this eucaryote originate from the C-2, -3 and -4 of glucose via ribose. PMID- 3089224 TI - Fluorescence energy transfer between Cys-10 residues in F-actin filaments. AB - Fluorescence energy transfer was measured between Cys-10 residues in an F-actin filament using 5-[2-((iodoacetyl)amino)-ethyl]aminonaphthalene-1-sulphonic acid (1,5-IAEDANS) as a fluorescence energy donor and 4-dimethylaminophenylazophenyl 4'-maleimide (DABMI) as the acceptor. Both labels were covalently attached to Cys 10 residues in an F-actin filament. Taking the helical structure of the F-actin filament into consideration, the radial coordinate of Cys-10 was calculated to be 23 A. This corresponds to a distance between adjacent sites along the long pitch helix of 56.1 A and along the genetic helix of 53.3 A. PMID- 3089225 TI - Intestinal first pass metabolism of amygdalin in the rat in vitro. AB - The intestinal first pass metabolism of amygdalin has been investigated in rat small intestine in vitro. The results show that amygdalin is hydrolyzed to prunasin, essentially in the wall of the proximal jejunum. This specific beta(1 6)hydrolytic cleavage of the terminal glucose residue is pH-dependent and can be inhibited by glucono-delta-lactone, a potent inhibitor of the lysosomal beta glucosidase of the rat intestine. No substrate competition between phloridzin and lactose vs amygdalin was noted. None of the more common soluble beta- or alpha enzymatic activities of mammalian intestine (alpha-glucosidase, alpha-amylase) or mammalian liver (beta-galactosidase, beta-glucuronidase) were capable of catalyzing the hydrolysis of the terminal glucose from amygdalin at pH's 5.0, 7.0 or 9.0. Furthermore, no metabolic activity of isolated rat livers toward amygdalin and prunasin was observed within two hours of recirculating perfusion. However, cecal contents of conventional rats, exhibited both amygdalin- and prunasin-hydrolyzing activities. The resulting mandelonitrile dissociates spontaneously into cyanide and benzaldehyde. Therefore, our findings indicate that metabolism of amygdalin to prunasin occurring in the proximal part of jejunum is apparently mediated by enzymatic beta(1-6)glucosidase activity of the gut wall. In contrast, the toxicity of amygdalin due to the release of cyanide obviously requires microbiological activities of the gut flora. PMID- 3089226 TI - Microsomal and cytosolic epoxide hydrolase in Drosophila melanogaster. AB - Subcellular fractions from Drosophila melanogaster and rat liver were investigated on their epoxide hydrolase activity. Both microsomes and the post microsomal supernatant of Drosophila appeared to contain epoxide hydrolase activity using styrene-7,8-oxide as the substrate. Based on body weight, these activities were in the same order of magnitude. Rat liver cytosol was able to catalyze the hydrolysis of styrene oxide only if the glutathione S-transferase activity was blocked. PMID- 3089228 TI - Occurrence and functional significance of serotonin and catecholamine uptake by astrocytes. PMID- 3089229 TI - Factors regulating prostaglandin E2 biosynthesis in renal cortical tubular cells. AB - Prostaglandin synthesis by isolated rat renal cortical tubular cells was studied in vitro with a superfusion system. The cells were introduced in Teflon chambers and intermittently stimulated. The PGE2 production was measured in the effluent. ANG II (10(-10)-10(-6)M) induced a dose-dependent increase in PGE2 synthesis. Saralasin antagonized the response to ANG II. Hyperosmolar mannitol or NaCl and Ca2+-ionophore A23187 also stimulated PGE2 synthesis. The PGE2 response to all stimuli was blocked in Ca2+-free media containing EGTA. The Ca2+-channel blocker nifedipine (10(-10)-10(-6)M) did not significantly inhibit the PGE2 response to ANG II, hyperosmolar mannitol or NaCl, and A23187, whereas the phospholipase inhibitors p-bromophenacyl bromide (10(-4)M) and chloroquine (10(-4)M) inhibited the response. Thus, PGE2 synthesis in response to these stimuli in rat renal cortical tubular cell is a Ca2+-dependent process, acting via phospholipases by a mechanism which does not appear to involve voltage-dependent Ca2+-channels. PMID- 3089227 TI - Effect of culture age on drug metabolizing enzymes and their induction in primary cultures of rat hepatocytes. AB - In order to further establish optimal and reproducible conditions for the use of primary hepatocyte cultures in studies of drug metabolism, the effect of culture age on the basal and induced activities of ethoxycoumarin O-deethylase (ECDE), UDP-glucuronyltransferase (GT) [methylumbelliferone (MU) and p-nitrophenol (pNP) as substrates] and sulfotransferase (MU) were measured. In contrast to the monooxygenase activity conjugating activities were maintained for 2-3 weeks in culture, although especially sulfate conjugation showed a transient decline during the first days, and GT activity increased later on during culture. Low induction of ECDE with both phenobarbital (PB) and 3-methylcholanthrene (MC) was seen during the first day in culture, and maximum induction was obtained when inducer was added on the second or third day. The MC inducible GT (pNP) exhibited a similar behaviour indicating that the coordinated induction of the MC inducible activities is preserved in culture. The results show that primary cultures of hepatocytes can be used to study conjugating enzymes and their regulation. However, each functional parameter that is to be investigated in hepatocyte cultures should first be studied as a function of culture age to establish the optimum time. PMID- 3089230 TI - Influence of temperature on the binding of sodium aurothiosulphate to human serum albumin. AB - The influence of temperature on the binding of aurothiosulphate by human serum albumin was studied in unbuffered solutions at pH 7.4 and ionic strength 0.15 M by means of equilibrium dialysis. It was found that the high affinity association constant was temperature dependent. The thermodynamic characteristics of binding delta G1 degrees less than 0, delta H1 degrees greater than 0 and delta S1 degrees greater than 0 indicated that the binding process was endothermic and entropically driven. It was concluded that electrostatic interaction was predominantly involved in the binding of aurothiosulphate to the high affinity binding site on albumin. This is consistent with the molecular mechanism that the ligand binds as Au+ to a sulfhydryl group of albumin by replacing a hydrogen ion. PMID- 3089231 TI - Effects of ligands on gold inhibition of selenium glutathione peroxidase. AB - Gold inhibits selenium-dependent glutathione peroxidase (GSH Px) in vitro. Chrysotherapy has been used for over five decades without complete understanding of its pharmacodynamics. This study shows that gold is potentially an inhibitor of GSH Px in vivo. Reported are conditions for assay of GSH-Px activity showing that the inhibition by gold species can be reversed. The study demonstrates the high affinity of gold for the selenohydryl-active site of GSH Px relative to the affinities of other physiological ligands; GSH Px was inhibited to a greater extent by a small molecular-weight fraction isolated from kidneys of gold-treated rats than by the fraction isolated from kidneys of rats not treated with gold. The data provide a new perspective on the action of gold-containing drugs in vivo. PMID- 3089232 TI - [Chemico-enzymatic synthesis of genetic elements for expression of synthetic genes in Bacillus subtilis cells]. AB - In order to obtain the recombinant Bacillus subtilis strain, a transcriptional translational control unit of the alpha-amylase gene of B. amyloliquefaciens was synthesized. The oligodeoxyribonucleotides were prepared by the modified triester method in solution and by the solid-phase approach. Then these oligonucleotides were joined by DNA ligase into two fragments which were cloned in the phage M13mp9 DNA and the plasmid pBR327. A plasmid harboring the site regulating the transcription of the alpha-amylase gene may be employed as vector for cloning the promoter-containing fragments in E. coli cells. PMID- 3089235 TI - Cost-benefit analysis--a framework for evaluating corporate health promotion programs. PMID- 3089233 TI - [Comparative pharmacology of glycerol-1-nitrate and glyceryl trinitrate in various species]. AB - The present studies yield that all 4 metabolites of glyceryl trinitrate (Nitro Mack, GTN) cause the same typical pharmacological effects as the parent substance. Continuous infusion of 4 mg/kg/min of glyceryl 1-nitrate (G-1-N) in the conscious dog results in a drop in blood pressure which is maintained for at least 20 min after stopping the infusion. Under comparable conditions the reduction in blood pressure caused by glyceryl 2-nitrate (G-2-N) (infused at 16 mg/kg/min) decreases by only 3 mmHg. The drop in blood pressure caused by a continuous infusion with GTN (8 micrograms/kg/min) disappeared 10 to 12 min after the end of the infusion. GTN is active in rat, dog and man for 15 to 30 min. Our experiments indicate that after oral administration to the rat or dog glyceryl 1,2-dinitrate (1,2-GDN) and glyceryl 1,3-dinitrate (1,2-GDN) are active for 3 h. Earlier experiments have shown that the administration of high oral doses of 1,2 GDN or 1,3-GDN (280 mg/kg) to the rat increases the time of action to 5-6 h. This is taken as indication that the dinitrates form pharmacologically active metabolites. 1,3-GDN (70 mg/kg p.o.) and 1,2-GDN (140 mg/kg p.o.) exhibited antianginal activity in the rat for 3 or 2 h, respectively. Orally administered GTN is only active for 15 min in the rat or dog. Its pharmacological activity after this time and up to 2-3 h on the rat (280 mg/kg p.o.) and on the dog (4 mg/kg p.o.) is brought about by the dinitrate metabolites (1,2-GDN, 1,3-GDN) and after this time probably only by G-1-N.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089234 TI - Collagen types in various layers of the human aorta and their changes with the atherosclerotic process. AB - The types of collagen components extracted from human aortas by repeated pepsin digestion were investigated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), after differential salt precipitation, cyanogen bromide (CNBr) cleavage and beta mercaptoethanol reduction. For further extraction of collagen components, repeated pepsin digestion was carried out, and two extracts, the former and latter, were obtained. The greatest increase was seen in type V collagen followed by type III in the former extract. Type I collagen was continually extracted, so the proportion of type I to other types became greater with the number of extractions. SDS-PAGE of the residue treated with CNBr revealed that it contained the greatest amount of type I, followed by the latter extract. Type I collagen comprised approximately two-thirds of the total collagen. It was the most predominant in the intima and adventitia but was also obviously abundant in the media. The proportion of type III collagen to total collagen fell slightly with advancing atherosclerosis, since the amounts of types I and V showed some increase. A band of the alpha 3(V) chain of type V collagen in the intima was occasionally detected between the bands of the alpha 1(V) and alpha 2(V) chains. Basement membrane collagen, type IV, which was extracted predominantly from the intima and subintima, showed a heterogenous distribution as to molecular size, ranging from 50 Kd to 140 Kd. The alpha 1(IV) and alpha 2(IV) collagens were found at positions corresponding to 100 Kd and 80 Kd, respectively. The content of collagen type IV also increased with the proliferative fibrotic process. Type VI collagen was found in the intima and subintima of the human aorta at a position corresponding to an approximate molecular weight of 150 Kd, and it was reduced to fragments of 40 Kd, 45 Kd and 52 Kd. PMID- 3089236 TI - Smoking and smoking cessation: occupational health issues. PMID- 3089237 TI - T-cell differentiation antigens and antigenic lymphocyte reactivity in pleural effusions. AB - Blood and pleural effusion mononuclear cells from thirteen patients were examined for the expression of T lymphocyte differentiation antigens as well as in vitro thymidine incorporation. The ratio of T4 to T8 cells was significantly greater among pleural effusion lymphocytes than among blood lymphocytes. Effusion lymphocyte responses to phytohaemagglutinin were less than those of blood lymphocytes. Unstimulated thymidine incorporation was greater in pleural effusion lymphocytes. Antigen-stimulated lymphocyte reactivity was not consistently greater in either blood or effusion lymphocytes. Lymphocytes from tuberculous effusions all reacted to tuberculin. Pleural effusion lymphocytes, regardless of the etiology of the effusion, possessed the same range of antigenic specificities as did blood lymphocytes. Therefore, effusion lymphocyte responsiveness to tuberculin does not prove the presence of tuberculous pleurisy but does indicate sensitisation to tuberculin. PMID- 3089238 TI - Sprain or fracture? An analysis of 2000 ankle injuries. AB - A retrospective survey of over 2000 patients with inversion injuries of the ankle joint was undertaken to examine the validity of criteria commonly used in an accident and emergency department to assess severity. Swelling alone is an unreliable indicator of the severity of the injury. Patients with severe pain and inability to weight bear show a high incidence of fractures and must be X-rayed. Conversely, a combination of minimal pain and swelling, and ability to bear weight are indicative of a soft-tissue injury. Young people sustain most inversion injuries and have a lower incidence of significant fractures of the lateral malleolus. Analysis of presenting features did not reveal any reliable indicants which could be used to reduce the number of radiographs requested, without substantially increasing the risk of missing patients with significant fractures. However, it has been possible to formulate guidelines for the more rational and consistent use of X-rays in the initial assessment of patients with ankle sprains. PMID- 3089239 TI - Computer graphics presentation modes for biologic data. Types and examples. AB - New advances in automated cytology, computer microscopy, densitometry and other instrumentation for feature/scene acquisition or analysis have resulted in higher information densities than heretofore encountered. Two-, three- and four-space computer graphics provide favorable bandwidth conditions for transforming complex, large-scale data sets into visual displays that allow a human observer, utilizing the brain's efficient processing of visual information, to rapidly grasp relationships and synthesize concepts. Examples of multidimensional displays are presented, all developed by neuroscientists who are not computer specialists. Because modern graphics and image-synthesis techniques can now be implemented on any one of several commercially available very-high-speed integrated-circuit-based display systems, at moderate cost, exploitation of specifically visual presentation should be carefully considered in any system generating information in high density. PMID- 3089240 TI - Protein and amino acid requirements of fishes. AB - Tentative qualitative and quantitative amino acid requirements have been reported for the major species of fish reared for market or as replacement stocks for natural waters. Most work has concentrated upon juvenile fish or upon rapidly growing young market fish; these have high protein dietary requirements (30-50%) that are in direct contrast to the homothermic terrestial animals. Net protein utilization from the diet is similar or slightly better than that found in avian species, but energy needs are much lower in fish and as a result the body protein deposition in fish is larger (about 5 g protein/MJ for the chick versus about 10 g protein/MJ for young fish). Qualitative amino acid requirements appear identical for all fish species examined; arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine are all required for normal growth and metabolism. Quantitative requirements differ only slightly among species that have been tested. Salmon have higher arginine requirements than other fish examined. Catfish appear to have a lower requirement for histidine and threonine, and the Japanese eel seems to need more tryptophan in the diet. However, when the quantitative requirements for indispensable amino acids are expressed as a percentage of the protein fed, then a remarkable harmony appears between values needed for maximal growth for most species examined. A review of Tables 3 and 4 will disclose the paucity of information available considering the large number of fish species reared commercially over the world. Most commercial diet formulations have relied upon the work done on salmon, catfish, and carp, and their amino acid and protein requirement values have been used. Remarkably, these diets have produced other species of fish economically. Sparing effects of one amino acid on another have only been studied with cystine methionine and tyrosine-phenylalanine. Arginine and analogues of methionine have been used as good nitrogen sources for salmon. Isoleucine-leucine ratios have been measured and experiments indicate some growth inhibition when the isoleucine leucine ratio was greater than 2/1. Valine at abnormally high levels also inhibited growth. Much more work needs to be done on the effects of subtle differences in amino acid ratios in the diet, and major emphasis should be placed on the important role of the dispensable amino acids in fish nutrition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3089241 TI - Inheritable biotin-treatable disorders and associated phenomena. PMID- 3089242 TI - Myocardial infarction in a young man with systemic lupus erythematosus, deep vein thrombosis, and antibodies to phospholipid. AB - From the age of 17 a young man had recurrent venous thrombosis, with pulmonary embolism on two occasions. Laboratory investigations showed increased DNA binding, thrombocytopenia, positive antinuclear antibodies, and immunoglobulin A deficiency. A plasminogen activator deficiency was suspected because the euglobulin lysis time was considerably prolonged. Variant lupus was diagnosed. He had a severe myocardial infarct at the age of 20 and subsequent investigations showed the presence in serum of the lupus anticoagulant and antibodies to cardiolipin. The presence of these antiphospholipid antibodies explains the features of his illness and establishes that this case fits into a subset of systemic lupus erythematosus characterised by thrombotic events. PMID- 3089243 TI - Experience with nitrobid (2% nitroglycerine) ointment as an aid to venepuncture. PMID- 3089244 TI - Differences in the effects of hypercapnia and hypoxia on the swallowing reflex in cats. AB - The effects of changes in PaCO2 and PaO2 on the swallowing reflex were studied in anaesthetized, vagotomized, paralysed and artificially ventilated cats. The swallowing reflex was induced by electrical stimulation of the superior laryngeal nerve (SLN). This initially suppressed activity in the phrenic nerve (PN). The swallowing reflex was then identified by a characteristic brief burst of PN activity and a large amplitude burst of hypoglossal nerve (HN) activity. Steady state responses to constant SLN stimulation for 60 s were measured at four carbon dioxide tensions (PaCO2 3.9, 5.1, 6.3 and 7.8 kPa) with hyperoxia (PaO2 greater than 51 kPa) and at four values of PaO2 (PaO2 56, 11.3, 6.9 and 4.8 kPa) at a fixed PaCO2 (PaCO2 4.2 kPa). Although both hypercapnia and hypoxia increased the spontaneous respiratory activity in PN and HN, the number of swallows elicited during SLN stimulation was not influenced by PaCO2, whereas a progressive decrease in the number of swallows with decreasing PaO2 was observed consistently. These results indicate that the swallowing reflex is independent of the background respiratory activity and that hypoxia depresses the swallowing reflex, whereas hypercapnia has no effect. PMID- 3089245 TI - Phenelzine induced grand mal seizure. PMID- 3089246 TI - The place of amiodarone in cardiology today. Proceedings of a symposium. Heathrow, London, 24-25 October 1985. PMID- 3089247 TI - Cellular electrophysiology of amiodarone in cardiac ischaemia. PMID- 3089248 TI - Amiodarone pharmacokinetics. PMID- 3089249 TI - Efficacy of amiodarone in patients with Chagas' disease and life-threatening arrhythmias. PMID- 3089250 TI - Use of amiodarone in childhood. PMID- 3089251 TI - Amiodarone dose titration: a method to minimise side effects during long term therapy. PMID- 3089252 TI - A practical regimen for intravenous amiodarone. PMID- 3089253 TI - The haemodynamic effect of intravenous amiodarone in patients with preserved left ventricular function. PMID- 3089254 TI - Intravenous amiodarone: UK clinical experience survey. PMID- 3089255 TI - Amiodarone in the management of atrial fibrillation complicating myocardial infarction. PMID- 3089256 TI - Clinical experience with amiodarone for treatment of recurrent ventricular tachycardia and ventricular fibrillation. PMID- 3089257 TI - Antiarrhythmic drugs in advanced organic heart disease. PMID- 3089258 TI - Amiodarone and the cardiomyopathies. PMID- 3089259 TI - Ventricular arrhythmias in heart failure; their significance and modification by amiodarone (with notes on the safety of combined therapy with captopril). PMID- 3089260 TI - Amiodarone for the conversion of established atrial fibrillation and flutter. PMID- 3089261 TI - Comparison between the efficacy of amiodarone and quinidine in the treatment of atrial cardiac arrhythmias. PMID- 3089262 TI - Amiodarone as a treatment for atrial fibrillation refractory to digoxin therapy. PMID- 3089264 TI - Amiodarone: a study of cutaneous photosensitivity. PMID- 3089263 TI - Comparison of amiodarone and disopyramide in the control of paroxysmal atrial fibrillation and atrial flutter (interim report). PMID- 3089265 TI - Amiodarone and the thyroid. PMID- 3089266 TI - Neurological and pulmonary adverse effects of amiodarone. PMID- 3089267 TI - Hepatic effects of amiodarone. PMID- 3089268 TI - Human electrophysiology: mechanisms of arrhythmia prevention and the action of amiodarone. PMID- 3089269 TI - Factor VIII concentrates contain factor VIII procoagulant antigen bound to phospholipid. AB - Fractionation of a human antibody to factor VIII: Ag by immunoabsorption with factor VIII/phospholipid (PL) complex has produced two pools of labelled Fab' fragments which can be used in fluid-phase immunoradiometric assays (IRMAs). One pool binds only to the PL-binding sites on factor VIII:Ag (and thus measures only that factor VIII:Ag in a sample not bound to PL), while the second binds to other antigenic sites. Parallel assays of factor VIII-containing materials using these two pools provide estimates of the proportion of factor VIII: Ag bound to PL in those materials. Five batches each of nine brands of factor VIII concentrates from eight different manufacturers were tested for PL-bound factor VIII:Ag by this method: all contained substantial amounts, ranging from 28% to 54% of the total factor VIII:Ag present. In addition, varying amounts of the factor VIII:Ag present in both non-activated and activated prothrombin complex concentrates (PCCs) from four manufacturers were PL-bound. PMID- 3089271 TI - The myelosuppressive effect of recombinant interferon gamma in short-term and long-term marrow cultures. AB - The effect of a highly purified human gamma IFN (r-gamma-IFN) on the growth of haemopoietic progenitors was examined in soft agar assays and in long-term bone marrow cultures. r-gamma-IFN reduced colony formation by progenitor cells of the granulocyte/macrophage lineage (GM-CFC), the erythroid lineage (BFU-E) and multipotent cells (GEMM-CFC), and suppressed haemopoiesis in long-term culture in a dose-related fashion. At high doses (1000 units/ml) r-gamma-IFN appeared to be toxic to the stromal cells of the bone marrow. PMID- 3089270 TI - Thrombocytopenia associated with gold therapy: a drug-induced autoimmune disease? AB - We studied 13 patients with rheumatoid arthritis (RA) and gold-induced thrombocytopenia. Platelet-specific autoantibodies of the IgG and often also of the IgM class were detected by immunofluorescence on the patient's platelets and in ether eluates from these platelets. In nine patients we also detected autoantibodies in the serum. The antibodies were unreactive with platelets from patients with Glanzmann's disease in most cases, and were not EDTA dependent. Thus, they had the serological characteristics of true autoantibodies. The reaction of the antibodies with platelets was not influenced by the addition of extra gold. By atomic absorption spectrophotometry we found that the ether eluates, which were often strongly reactive with donor platelets, were free of gold. This indicated that the autoantibodies in the thrombocytopenic patients were not dependent on gold for their reaction. The possibility is raised that gold treatment of rheumatoid arthritis patients induces or enhances the formation of platelet-specific autoantibodies, and that gold-induced thrombocytopenia is a drug-induced autoimmune disease. PMID- 3089272 TI - An acute leukaemia augured before clinical signs by blood group antigen abnormalities and low levels of A and H blood group transferase activities in erythrocytes. AB - A mixed field agglutination pattern with anti-A reagents and very low levels of A and H blood group antigen specific transferase activities were found in the erythrocytes of a 4-year-old girl who presented no clinical signs of haematological disease. Blood and marrow examination displayed some features consistent with a moderate dysmyelopoietic state. 18 months later an acute myeloblastic leukaemia confirmed the suspected haematological malignancy. PMID- 3089273 TI - Immunohistological localization of factor VIII in placental endothelial cells. AB - DNA-recombinant studies have established that factor VIII-mRNA is present in liver and placental tissue. In a previous immunohistological study using monoclonal antibodies we have localized factor VIII in liver sinusoidal endothelial cells. In this paper we demonstrate that also the endothelial cells lining the fetal vessels in human placenta contain factor VIII. Based on the combined results of the present study and a previous study we favour the concept that factor VIII is synthesized in placental endothelial cells. PMID- 3089274 TI - Antibacterial activity in human amniotic fluid: dependence on divalent cations. AB - Antibacterial activity, tested against Bacillus subtilis, was present in all 34 samples of human amniotic fluid collected between 37 and 41 weeks gestation. High molecular-weight (beta-lysin) antibacterial activity was reduced after treatment with ethylene diamine tetra-acetic acid (EDTA), but not after treatment with 1, 10-phenanthroline or diphenylthiocarbazone. The activity was restored following incubation with magnesium, calcium, or zinc. Low-molecular-weight antibacterial activity (less than 1000 daltons) in acid-alcohol extracts was reduced after treatment with dithizone, but not after treatment with EDTA or 1, 10 phenanthroline. Activity was restored after treatment with manganese, cobalt or zinc. High-molecular-weight (beta-lysin) activity was therefore biochemically similar to serum beta-lysin but biochemically different from the low-molecular weight antibacterial component of amniotic fluid. PMID- 3089275 TI - Noncovalent intercalative complex formation and kinetic flow linear dichroism of racemic syn- and anti-benzo[a]pyrenediol epoxide-DNA solutions. AB - In order to gain a better understanding of the molecular basis underlying the differences in biological activities of the diastereomeric syn and anti diol epoxides of benzo[a]pyrene (trans-7,8-dihydroxy-syn-9,10-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene, respectively), their interactions with DNA in aqueous solutions were studied and compared. Kinetic flow linear dichroism experiments indicate that both diastereomers (racemic mixtures) form intercalation complexes immediately after mixing; the association constant (23 degrees C, ionic strength approximately 0.005) is significantly smaller (5200 M-1) in the case of the syn than in the case of the anti diastereomer (12 200 M-1). This difference is attributed to the greater bulkiness of the 7,8,9,10 ring of the syn stereoisomer, which is in the quasi-diaxial conformation as compared to the less bulky quasi diequatorial conformation of the anti diastereomer. In contrast, the intercalative association constants of the tetraols derived from the hydrolysis of the two diol epoxides are similar in value. Upon formation of noncovalent syn BPDE-DNA intercalation complexes, the reaction rate constant for the formation of tetraols (approximately 98%) and covalent adducts (approximately 2%) increases from 0.009 to 0.05 s-1 at pH 9.5 in 5 mM tris(hydroxymethyl)aminomethane buffer. The conformations of the aromatic chromophores of BPDE were followed by the kinetic flow dichroism technique as a function of reaction time; while the anti diastereomer changes conformation from an intercalative to an apparently external binding site, the syn diol epoxide molecules do not appear to undergo any measurable reorientation during or after the covalent binding reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089276 TI - Trapping and partial characterization of an adduct postulated to be the covalent catalytic ternary complex of thymidylate synthase. AB - The proposed mechanism of action of thymidylate synthase envisages the formation of a covalent ternary complex of the enzyme with the substrate dUMP and the cofactor 5,10-methylenetetrahydrofolate (CH2H4folate). The proposed structure of this adduct has been based by analogy on that of the covalent inhibitory ternary complex thymidylate synthase-FdUMP-CH2H4folate. Our recent success in using the protein precipitant trichloroacetic acid to trap the latter complex and covalent binary complexes of the enzyme with FdUMP, dUMP, and dTMP led to the use of this technique in attempts to trap the transient putative covalent catalytic ternary complex. Experiments performed with [2-14C]dUMP and [3',5',7,9-3H]CH2H4folate show that both the substrate and the cofactor remained bound to the protein after precipitation with trichloroacetic acid. The trapped putative covalent catalytic complex was subjected to CNBr fragmentation, and the resulting peptides were fractionated by reverse-phase high-pressure liquid chromatography. The isolated active site peptide was shown to retain the two ligands and was further characterized by a limited sequence analysis using the dansyl Edman procedure. The inhibitory ternary complex, which was formed with [14C]FdUMP and [3H]CH2H4folate, served as a control. The active site peptide isolated from the CNBr-treated inhibitory ternary complex was also subjected to sequence analysis. The two peptides exhibited identical sequences for the first four residues from the N-terminus, Ala-Leu-Pro-Pro, and the fifth amino acid residue was found to be associated with the labeled nucleotides and the cofactor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089277 TI - The modulating effects of lipids on purified rat liver Golgi galactosyltransferase. AB - Galactosyltransferase was purified from rat liver Golgi membranes. The Triton X 100, used to solubilize the enzyme was removed immediately prior to the lipid interaction studies. In lipid vesicles, prepared from a variety of phosphatidylcholines (PCs), including egg PC, DOPC, DMPC, DPPC and DSPC, the ability of the lipids to stimulate the enzyme decreased in the order egg PC greater than DOPC greater than DMPC greater than DPPC greater than DSPC, i.e. the lower the transition temperature (Tc) the greater the stimulation of the enzyme. A second, neutral lipid, phosphatidylethanolamine was used to permit a comparison of the effect of a different head group of the same net charge at neutral pH. The PEs included, egg PE, soy PE, Pl-PE, PE(PC) and DPPE in order of increasing Tc. The effect of the PEs was opposite to that of the PCs, i.e. the higher the Tc, the greater the stimulation of the enzyme. In fact egg PE and soy PE which have the lowest Tc values were inhibitory. Thus the modulation of the Golgi membrane galactosyltransferase by these lipids was different from that reported earlier for the bovine milk galactosyltransferase. The effects of two acidic lipids, egg phosphatidic acid (PA) and egg phosphatidylglycerol (PG) were studied also. Both totally inhibited the enzyme even at low concentrations of lipid, however, the PA was more effective than PG. In mixtures of neutral lipid (PC) and acidic lipid (PA or PG), the effect of the acidic lipid dominated. Even in the presence of excess PC, total inhibition of the enzyme was observed. It was concluded that the enzyme bound the acidic lipid preferentially to itself. The choice of the lipids allowed us to make several direct comparisons concerning the effect of the nature of the lipid head group on the activity of the enzyme. For example PE(PC), egg PA and egg PG would have fatty acid chains identical to egg PC since these three lipids are all prepared by modification of egg PC. As well, DPPE differs from DPPC only by nature of the head group. These comparisons indicated that not only the net charge but also chemical nature of the head group were important in the lipid modulation of Golgi galactosyltransferase. PMID- 3089278 TI - Studies on calcium binding to brush-border membranes from rabbit small intestine. AB - A study was made of the uptake of Ca2+ by brush-border membrane vesicles prepared from rabbit small intestine. The process was found to be time, temperature and substrate concentration dependent, displayed saturability, did not depend on added energy sources and occurred optimally in a pH range of 7.5-8.0. Although the transport of D-glucose by these membrane vesicles responded to changes in osmotic pressure as modified by adding cellobiose to the medium, the uptake of Ca2+ was found not to be osmotically-sensitive. Moreover, the equilibrium uptake value obtained when vesicles were exposed to 0.36 mM Ca2+ was some 60-fold higher than the amount that could have been accommodated by the intravesicular space, calculated from the equilibrium uptake of D-glucose. It was concluded from these results that the uptake involved complete binding of the Ca2+ to the membrane. The ionophore A23187 enhanced the rates of uptake and efflux of Ca2+ without affecting equilibrium values, which suggests that the binding of Ca2+ measured under our conditions was to interior sites of the membrane. The binding capacity was decreased in the presence of 10 mM lidocaine as indicated by a diminution of the equilibrium binding values. Generating an electrochemical potential (negative inside) by addition of valinomycin to vesicles pre-equilibrated with K2SO4, enhanced the rate of uptake of Ca2+. Addition of metal ions, on the other hand, inhibited the uptake, La3+ and Tb3+ being most effective followed by Mn2+, Ba2+ and Mg2+. Na+ and K+ were the least inhibitory. The properties of the Ca2+ uptake process found in rabbit brush-border membranes were compared to those of similar processes occurring in other species. PMID- 3089279 TI - Vitamin E in young and old human red blood cells . AB - Young and old human red blood cells contain about the same amount of alpha tocopherol, a compound which has previously been shown to be the major lipid soluble, chain-breaking antioxidant present in such cells. Since red blood cells lose up to ca. 20% of lipid material from their membrane as they age, the alpha tocopherol/membrane-lipid ratio actually rises with age rather than declining as might have been expected on the basis of the free radical theory of aging. The alpha-tocopherol/arachidonic acid moiety ratios increase in the order: young red blood cells less than old red blood cells less than plasma, which argues against the suggested membrane stabilizing effect of alpha-tocopherol/arachidonic acid moiety complexes. PMID- 3089280 TI - Inflammatory infiltrates of experimental mammary cancers. AB - The purpose of this review was to summarize observations on the type and function of inflammatory infiltrates of mouse mammary tumors and to speculate on the underlying mechanisms and the significance of infiltrates to mammary tumor biology. Although the major conclusion is that much more work is needed, certain themes seem to be emerging. The number of infiltrating cells can be very high but is unrelated to biological behavior of the tumors. What seems to be important is the relative contributions of inflammatory cell subsets. In the case of T-cell subsets and NK cells, the infiltrates from tumors of long-term cell lines so far seem uninformative. The general characteristics are similar to those of infiltrates from rapidly proliferating, normal mammary tissues. These characteristics do not correlate with diverse biological behavior or malignant potential. A more informative model appears to be one in which the development of tumors from preneoplastic tissue can be observed. Here our attention is currently focused on NK cells. By contrast, the correlation between activated TAM and metastatic behavior suggests that our transplantable MMT lines may be biologically relevant in the study of infiltrating macrophages. We are especially interested in the role of TAM in the generation of tumor cell variability. Overall, our data indicate that the host infiltrate is another manifestation of both inter- and intra-tumor heterogeneity and, as such, is not simply a response to, but, rather, a part of the tumor ecosystem. Unraveling the cellular and molecular mechanisms that govern the inflammatory cell component of tumors should provide insight into the types of cellular interactions that result in tumor development and progression. PMID- 3089281 TI - Kinetic, equilibrium and spectroscopic studies on cation association at the active center of acetylcholinesterase: topographic distinction between trimethyl and trimethylammonium sites. AB - This study examines the importance of electrostatic interactions on ligand association at the active center of acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7). The active-center serine was covalently modified with the dimensionally equivalent isosteric beta-(trimethylammonium)ethyl and 3,3 dimethylbutyl methylphosphonofluoridates. Reactivation of the 3,3-dimethylbutyl methylphosphono-conjugate by the bisquaternary mono-oxime HI-6, after accounting for the capacity for spontaneous reactivation, proceeded at a rate that was 20 fold greater than that for the cationic conjugate. Decidium, a fluorescent bisquaternary ligand that binds with its trimethylammonium moiety within the active center, exhibited affinity for the 3,3-dimethylbutyl conjugate that was within 2-fold that for the native enzyme, but 100-fold greater than for the cationic conjugate. Whereas association of n-alkyl mono- and bisquaternary ligands with the uncharged conjugate was virtually unaltered with respect to the native enzyme, the affinities of edrophonium, phenyltrimethylammonium and N methylacridinium were reduced 100-fold for the uncharged conjugate relative to native enzyme. These results indicate that the orientations of the 3,3 dimethylbutyl and beta-(trimethylammonium)ethyl moieties with respect to the surface of the enzyme are not equivalent, that modification of the active center does not preclude cation association of active-center-selective ligands, and that aromatic cations associate at an anionic locus which is unique from that at which decidium and the n-alkyl mono- and bisquaternary cations associate. As such, the results point to the presence of a heterogeneity of cation binding sites within a circumscribed distance from the modified serine, and do not sustain the view proposed by Hasan et al. (J. Biol. Chem. 255 (1980) 3898-3904; 256, (1981) 7781 7785) that electrostatic interactions at the active center are subordinate to steric constraints imposed by a dimensionally restricted trimethyl site. PMID- 3089282 TI - Purification and characterization of, and preparation of an antibody to, transketolase from human red blood cells. AB - Transketolase (sedoheptulose-7-phosphate: D-glyceraldehyde-3-phosphate glycolaldehydetransferase, EC 2.2.1.1) was purified 16 000-fold from human red blood cells, using DEAE-Sephadex A-50, Sephadex G-150, FPLC on Mono P, and Sephadex G-100. The purified enzyme migrated as a single protein band on SDS polyacrylamide gel electrophoresis. The FPLC step resolved transketolase into three peaks, designated I, II and III. From results of re-FPLC on Mono P, SDS polyacrylamide gel electrophoresis, gel filtration, catalytic studies, amino acid analysis and immunological studies, it was concluded that I, II and III were originally the same protein, modified during storage and purification. Transketolase had a subunit (Mr 70 000) and appeared to be composed of two identical subunits. 1 mol of subunit contained 0.9 mol of thiamine pyrophosphate. The pH optimum of the reaction lay within the range 7.6-8.0, and the Km values were determined to be 1.5 X 10(-4) M for xylulose 5-phosphate and 4.0 X 10(-4) M for ribose 5-phosphate. Hg2+ and p-chloromercuribenzoate inhibited the enzyme reaction, and the inhibition of the latter disappeared upon the addition of cysteine. Thiamine and its phosphate esters did not, but cysteine (1 X 10(-2) M) and ethanol (10% and 1% v/v) did activate the enzyme reaction. Antibody prepared to II bound all forms of transketolase in the hemolysate, but inhibited the reaction only about 20%. PMID- 3089283 TI - Immunochemical characterization of human liver and heart ferritins with monoclonal antibodies. AB - A library of 27 murine monoclonal antibodies was obtained by using human liver and heart ferritins as immunogens. The specificity of the antibodies for the two ferritins and their subunits was studied with five different methods. The antibodies elicited by the liver ferritin bound preferentially the immunogen and were specific for the L subunit. Some antibodies elicited by the heart ferritin had characteristics similar to the anti-liver antibodies, other ones bound preferentially the heart over the liver ferritin and were specific for the H subunit. Only two antibodies were able to bind both ferritins and subunits. Some anti-H and anti-L chain antibodies were used to develop and compare four types of immunoassay to quantitate isoferritins. The results indicate that heart ferritin is immunologically more heterogeneous than liver, the H and L subunits having large immunological differences with few, if any, identical epitopes; and that that the architecture of the immunoassays have a strong influence on the crossreactivity of the antibodies with the two isoferritins, probably because H and L chains are not arranged randomly in the assembled protein. PMID- 3089284 TI - Fluorescence resonance energy transfer between the nucleotide binding site and Cys-10 in G-actin and F-actin. AB - Intramonomer fluorescence resonance energy transfer between the donor epsilon-ATP bound to the nucleotide site and the acceptor N-(4-dimethylamino-3,5 dinitrophenyl)maleimide (DDPM) or 4-dimethylaminophenyl-azophenyl-4'-maleimide bound to Cys-10 in G-actin was measured. The donor-acceptor distance was calculated to be about 40 A. The intermonomer energy transfer in F-actin occurring between epsilon-ADP and DABMI was also measured. The radial coordinate of Cys-10 was calculated to be 25 A based on the helical symmetry of F-actin and the recently calculated radial coordinate of the nucleotide binding site in F actin i.e. 25 A (Miki, M., Hambly, B. and dos Remedios, C.G. (1986) Biochim. Biophys. Acta 871, 137-141). (The assumption has been made in calculating these distances that the energy donor and acceptor rotate rapidly relative to the fluorescence lifetime.) Corresponding distances separating the donor nucleotide in one monomer from acceptors on Cys-10 in the first and second nearest neighbours in F-actin are 39-40 A and 41-43 A. PMID- 3089285 TI - Localization of lysine residues in the binding domain of the K99 fibrillar subunit of enterotoxigenic Escherichia coli. AB - Modification of lysine residues with 4-chloro-3,5-dinitrobenzoate results in the loss of the binding capacity of K99 fibrillae to horse erythrocytes (Jacobs, A.A.C., van Mechelen, J.R. and de Graaf, F.K. (1985) Biochim. Biophys. Acta 832, 148-155). In the present study we used dinitrobenzoate as a spectral probe to map the modified residues. After the incorporation of 0.7 mol CDNB per mol subunit, 90% of the binding activity disappeared and the lysine residues at positions 87, 132 and 133 incorporated 20%, 27.5% and 52.2% of the totally incorporated label, respectively. In the presence of the glycolipid receptor, Lys-132 and Lys-133 were partially protected against modification, while Lys-87 was not protected. The results suggest that Lys-132 and Lys-133 are part of the receptor-binding domain of the K99 fibrillar subunit and that the positive charges on these residues are important for the interaction of the fibrillae with the negatively charged sialic acid residue of the glycolipid receptor. A striking homology was found between a six-amino-acid residue segment of K99, containing Lys-132 and Lys 133, and segments of three other sialic-acid-specific lectins; cholera toxin B subunit, heat-labile toxin B subunit of Escherichia coli and CFA1 fimbrial subunit, suggesting that these segments might also be part of the receptor binding domain in these three proteins. PMID- 3089286 TI - Optimization of hydroxylation of tyrosine and tyrosine-containing peptides by mushroom tyrosinase. AB - Free tyrosine and tyrosine residues in various peptides and proteins are converted into dopa and dopa residues by tyrosinase (monophenol,L-dopa:oxygen oxidoreductase, EC 1.14.18.1) in the presence of reductants. The efficiency of the tyrosine-to-dopa conversion was examined under varied conditions, such as the substrate-to-tyrosine ratio, concentrations of reductant and oxygen in the reaction solution, pH, temperature and reaction time. The highest dopa yields were achieved with the following optimal conditions for hydroxylation: 0.1 M phosphate buffer at pH 7, 25 mM ascorbic acid, 1 mM tyrosine, 50 micrograms/ml tyrosinase and 20 degrees C. Using these conditions, up to 70% of free tyrosine was converted into dopa, and tyrosine residues in several synthetic peptides were also hydroxylated to dopa residues at ratios as high as free tyrosine. The preparation of hydroxylated analogues of the decapeptide (Ala-Lys-Pro-Ser-Tyr-Pro Pro-Thr-Tyr-Lys), in particular, may contribute to a better understanding of adhesion in the dopa-containing mussel glue protein. PMID- 3089287 TI - Proton nuclear magnetic resonance studies on the kinetics of tryptic fragments of calmodulin upon calcium binding. AB - The kinetics of the Ca2+-dependent conformational change of the tryptic fragments F12 (residues 1-75) and F34 (residues 78-148) of calmodulin were studied by 1H NMR. Resonances of two phenylalanines, 16 (or 19) and 65 (or 68), N epsilon, N epsilon, N epsilon-trimethyllysine-115 and tyrosine-138 were examined by the saturation-transfer technique or computer-aided line-shape simulation to obtain the rate of the conformational exchange between the Ca2+-free form and the Ca2+ bound form. The rates for F12 and F34 in the presence of 0.2 M KCl at 22 degrees C were 300-500 s-1 and 3-10 s-1, respectively. Activation parameters are as follows: Delta H not equal to = 11(+/- 2) kcal X M-1 and delta S not equal to = 9(+/- 5) cal X K-1 X M-1 for F12, and delta H not equal to = 16(+/- 2) kcal X M-1 and delta S not equal to = -2(+/- 5) cal X K-1 X M-1 for F34. These kinetic data for the conformational exchange are in agreement with those of Ca2+ dissociation from the binding sites obtained by 43Ca-NMR and stopped-flow fluorescence studies. PMID- 3089288 TI - Phospholipase C and diacylglycerol lipase activities associated with plasma membranes of chromaffin cells isolated from bovine adrenal medulla. AB - The plasma membranes of bovine adrenal chromaffin cells were isolated and the activities of enzymes involved in arachidonic acid liberation were investigated. Only a minute activity of phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) could be detected using externally added phosphatidylcholine (PC) and phosphatidylethanolamine (PE) as substrate. When membranes were treated with exogenous phospholipase C (orthophosphoric acid diester phosphohydrolase, EC 3.1.4.1) there was a liberation of free fatty acids from the sn-2 position of PC. The enzyme responsible for this effect could be demonstrated to be a diacylglycerol lipase (glycerol ester hydrolase, EC 3.1.1.3) localized in the plasma membrane. Using phosphatidylinositol (PI) as a substrate, it was found that an endogenous phospholipase C exists which co-purifies with the membrane preparation. The produced diacylglycerol is subsequently hydrolyzed by diacylglycerol lipase liberating arachidonic acid. The two enzymes, phospholipase C and diacylglycerol lipase were characterized. Phospholipase C was found to be calcium dependent and PI specific, showing an activity of 60 pmol/micrograms protein per h (1.2 mM Ca2+), whereas the diacylglycerol lipase was calcium independent hydrolyzing diacylglycerol at a rate of 7.2 pmol/micrograms protein per h. The lipase but not the phospholipase C was inhibited 50% by 1.7 mM para bromophenacylbromide. PMID- 3089289 TI - Appearance of the arachidonic acid metabolic pathway in human promyelocytic leukemia (HL-60) cells during monocytic differentiation: enhancement of thromboxane synthesis by 1 alpha,25-dihydroxyvitamin D-3. AB - The appearance of the arachidonic acid metabolic pathway in human promyelocytic leukemia (HL-60) cells was investigated during 1 alpha,25-dihydroxyvitamin D-3 induced monocytic differentiation. 1 alpha,25-Dihydroxyvitamin D-3-treated HL-60 cells acquired the ability to convert [1-14C]arachidonic acid to thromboxane B2 and prostaglandin E2 during monocytic differentiation. The major cyclooxygenase product synthesized by the HL-60 cells after 3-4 days exposure to 1 alpha,25- dihydroxyvitamin D-3 (48 nM) was thromboxane B2 and its production was about 19 25-times higher than that of untreated HL-60 cells. The percent conversion of thromboxane B2 from [1-14C]arachidonic acid in the 1 alpha,25-dihydroxyvitamin D 3 (48 nM, 3 day exposure)-treated HL-60 cells was about 4.4% as compared to that (about 0.3%) of the untreated cells, whereas the percent conversion of thromboxane B2 from [1-14C]prostaglandin H2 in the 1 alpha,25-dihydroxyvitamin D 3-treated cell homogenate was about 22.4% as compared to that (about 13.6%) of the untreated cell homogenate. The stimulatory effect of 1 alpha,25 dihydroxyvitamin D-3 on thromboxane B2 production from [1-14C]arachidonic acid and from [1-14C]prostaglandin H2 in HL-60 cells was inhibited by the addition of cycloheximide (1 microgram/ml). However, 1 alpha,25-dihydroxyvitamin D-3 (48 nM) did not significantly stimulate the arachidonic acid release either in HL-60 cells or in 1 alpha,25-dihydroxyvitamin D-3-induced cells. These results suggest that the stimulatory effect of 1 alpha,25-dihydroxyvitamin D-3 on the thromboxane production in HL-60 cells was not due to the activation of phospholipase A2 but due to the induction of fatty acid cyclooxygenase and thromboxane synthetase activities. Thromboxane A2 actively produced during the monocytic differentiation of HL-60 cells could influence the cell adhesiveness of the monocyte-macrophage differentiated cells. PMID- 3089290 TI - Novel biological transformations of 15-Ls-hydroperoxy-5,8,11,13-eicosatetraenoic acid. AB - [1-14C]Arachidonic acid was incubated with homogenates of the fungus, Saprolegnia parasitica. The products consisted of comparable amounts of two epoxy alcohols, 15-Ls-hydroxy-11,12-epoxy-5cis,8cis,13trans- eicosatrienoic acid and 15-hydroxy 13,14-epoxy-5cis,8cis,11cis-eicosatrienoic acid. Results of incubations carried out in the presence of nordihydroguaiaretic acid, 5,8,11,14-eicosatetraynoic acid, p-hydroxymercuribenzoate as well as glutathione peroxidase plus reduced glutathione demonstrated that transformation of arachidonic acid into epoxy alcohols occurred with the formation of 15-Ls-hydroperoxy-5cis,8cis,11cis,13trans eicosatetraenoic acid (15-HPETE) as an intermediate. The pathway involved a lipoxygenase catalyzing the oxygenation of arachidonic acid at the 15L position to produce 15-HPETE, and a hydroperoxide isomerase activity which catalyzed conversion of 15-HPETE into the two epoxy alcohols. Studies with 15-[18O2]HPETE demonstrated that both oxygens of 15-HPETE were retained in the epoxy alcohols. Furthermore, experiments with mixtures of 15-[18O2]-and 15-[16O2]HPETE showed that conversion of 15-HPETE into epoxy alcohols occurred by an intramolecular transfer of hydroperoxide oxygen. PMID- 3089291 TI - Phospholipid fatty acid composition of pulmonary airway epithelial cells: potential substrates for oxygenation. AB - To determine possible substrates for airway epithelial lipoxygenase and cyclooxygenase activities, we examined the amounts and distributions of fatty acids in phospholipids of human, dog and sheep airway epithelial cells. We found that the cells contained significant levels of n-6 and n-3 fatty acids in species specific amounts: dog cells were relatively enriched in the n-6 series and poor in n-3, while sheep cells were enriched in the n-3 series and poor in n-6. Despite differences in fatty acid content, cells from each species expressed a constant phospholipid composition and distributed their n-6 and n-3 fatty acids in a stereotyped fashion among phospholipid classes. The analysis shows that the species differences in oxygenation activities reported previously are paralleled by heterogeneity in potential substrates. PMID- 3089292 TI - Human breast milk contains a factor which markedly stimulates aortic prostacyclin synthesis. AB - Human breast milk has been shown to contain a potent factor which markedly stimulates the synthesis of prostacyclin by rabbit aorta. The stimulatory effect of colostrum was modest when compared to mature milk. This factor appears to be protein in nature with a molecular weight of less than 10 000. The main site of action of the factor appears to be on the conversion of arachidonic acid into prostacyclin. This factor might have a role in the optimal development of prostacyclin synthetic pathways which are not fully developed at birth. PMID- 3089293 TI - C6-C10-dicarboxylic acids in liver and kidney tissue in normal, diabetic ketotic and clofibrate-treated rats. AB - A combined gas chromatographic-mass spectrometric method (selected ion monitoring) to determine C6-C10-dicarboxylic acids in liver and kidney tissue is reported. Alterations in tissue concentrations of the dicarboxylic acids were reflected in urinary excretions, i.e., diabetic rats with 'ketotic dicarboxylic aciduria' had corresponding elevated concentrations of short-chain dicarboxylic acids in liver and kidney tissue. Stimulation of the enzymes of fatty acid oxidation by clofibrate was, as a sole event, not sufficient to cause elevated tissue concentrations of dicarboxylic acids, nor did it result in dicarboxylic aciduria, probably because of a relative lack in substrate (fatty acids) compared to the diabetic ketotic state, where lipolysis is increased. These results strongly indicate that 'ketotic dicarboxylic aciduria' parallels the activity of the lipid metabolism at cellular level, and that it is not just a matter of renal handling. PMID- 3089294 TI - Effect of elastase on prostacyclin synthesis in aortic smooth muscle cells. AB - The effects of elastase on prostacyclin biosynthesis in cultured rat aortic smooth muscle cells were investigated. Prostacyclin is the major product formed from arachidonic acid by aortic smooth muscle cells. When intact cells were incubated with elastase, a significant stimulatory effect on prostacyclin biosynthetic activity in cells was evident. However, the addition of elastase directly to the cell-free homogenates did not show any effects on prostacyclin biosynthesis. The maximal effect of elastase on the stimulation of prostacyclin biosynthesis without any cellular damage was observed at a concentration of 50 unit/ml elastase. Elastase also caused a marked release of arachidonic acid. At higher concentrations of elastase (75-100 units/ml), the release of arachidonic acid and prostacyclin synthesis was observed, but, at these concentrations of elastase, cells were slightly damaged. On the other hand, the releases of prostacyclin and arachidonic acid were markedly enhanced, when cells were preincubated with elastase (1 unit/ml) for 3 days. These results indicate that elastase, even at low concentrations, causes the releases of arachidonic acid and prostacyclin, especially when aortic smooth muscle cells are pre-treated with elastase. PMID- 3089295 TI - The role of apolipoprotein A-IV in reverse cholesterol transport studied with cultured cells and liposomes derived from an ether analog of phosphatidylcholine. AB - Cholesterol efflux was studied in a model system in culture using apolipoproteins and phospholipids added in the form of liposomes at concentrations expected to be present in the extracellular fluid. Fibroblasts were seeded in medium containing [3H]cholesterol-labeled serum, grown till confluent, and the [3H]cholesterol efflux was studied in serum-free medium. Addition of delipidated HDL apolipoprotein resulted in a very low release of [3H]cholesterol, which did not increase with time of exposure or concentration of apolipoproteins. Addition of increasing amounts of HDL apolipoprotein to liposomes prepared from either dioleoylphosphatidylcholine (PC) or its nonhydrolysable ether analog, dioleylphosphatidylcholine (DOEPC) resulted in a 3-5-fold increase of [3H]cholesterol efflux, over that achieved with liposomes alone. This model system permitted the test of the putative role of apolipoprotein A-IV in cholesterol removal from cells. The ability of apolipoprotein A-IV to enhance [3H]cholesterol efflux from cells by DOEPC liposomes was compared to that of apolipoproteins A-I, E and C, which were added at equimolar concentrations. At nM concentrations, apolipoproteins A-IV, A-I and E were equally able to enhance cholesterol efflux, while C apolipoproteins were less effective at these low concentrations. Mixtures prepared from apolipoprotein A-IV, A-I and E and PC or DOEPC liposomes were equally effective in cholesterol removal, while phosphatidylethanolamine liposome apolipoprotein mixtures had a much lower capacity. The present study provides the first evidence that apolipoprotein A-IV can play a role in reverse cholesterol transport as was suggested on the basis of high concentrations of this apolipoprotein in nonlipoprotein form in plasma and extracellular fluid. The efficacy of DOEPC liposomes to serve as cholesterol acceptors might be of potential value for enhancement of reverse cholesterol transport in vivo. PMID- 3089296 TI - Stereospecific induction of rat liver bilirubin UDPglucuronosyltransferase and lauric acid 12-hydroxylation by the isomers of 2-phenylpropionic acid. AB - The inductive effects of racemic 2-phenylpropionic acid and its isomers on rat liver bilirubin UDP-glucuronosyltransferase activity and lauric acid 12 hydroxylation (cytochrome P-452-dependent) were compared. The (S)-(+)-enantiomer and the racemic mixture gave the greatest induction of both enzyme activities, whereas (R)-(-)-2-phenylpropionic acid produced increases of only one-third of those of its antipode. The determination of the enantiomeric composition of the excreted 2-phenylpropionic acid after a single oral dose indicated that the (R)-( )-enantiomer given as such or in the racemate was inverted to its antipode, which strongly suggests that (S)-(+)-2-phenylpropionic acid is responsible for the inductive effects observed. The demonstration of the same stereospecificity for the induction of bilirubin UDPglucuronosyltransferase and lauric acid 12 hydroxylation further indicates a close mechanistic link between these two processes. PMID- 3089297 TI - Stimulus-aggregation coupling in platelets activated with PAF-acether. AB - Contrary to most agonists, platelet-activating factor (PAF-acether) induces a more pronounced aggregation at 22 degrees C than at 37 degrees C. A possible explanation was sought in the mechanism that couples the PAF-acether-receptor complex with exposure and occupation of fibrinogen binding sites. Comparison of studies performed at 37 degrees C with those at 22 degrees C revealed: a faster binding of [3H]PAF-acether to its receptors; more accumulation of 32P-labelled phosphatidylinositol 4-monophosphate and a slower but more abundant formation of phosphatidic acid that lasted for 5 min; a 1.4-fold increase in phosphorylation of the Mr 47,000 protein and a 2-fold increase in phosphorylation of the myosin light chain. In contrast, less secretion occurred and less [32P]phosphatidylinositol accumulated at 22 degrees C than at 37 degrees C, and also the increase in cytosolic Ca2+ content and the formation of thromboxane B2 were considerably lower. No differences were found in [32P]phosphatidylinositol 4,5-bisphosphate formation and arachidonate metabolism. Fibrinogen binding studies revealed two types of binding at both temperatures, a high-affinity and a low-affinity binding. There were 6-fold more low-affinity binding sites at 22 degrees C than at 37 degrees C, whereas high-affinity binding did not change. These data suggest that the better aggregation found at 22 degrees C is the result of exposure of an increased number of fibrinogen binding sites. The increased protein phosphorylation and phosphatidic acid accumulation and the faster binding of PAF-acether to its receptors which accompany the better aggregation responses at 22 degrees C suggest that these processes are involved in the regulation of exposure of fibrinogen binding sites. PMID- 3089298 TI - Reexamination of the structure of eumelanin. AB - The generally accepted concept that the black melanin eumelanin is made mostly from 5,6-dihydroxyindole but not from 5,6-dihydroxyindole-2-carboxylic acid (DHIC) was reexamined by comparison of synthetic and natural eumelanins. The analytical methods used were elemental analysis and determination of the carboxyl group by acid treatment to yield CO2 and by permanganate oxidation to yield pyrrole-2,3,5-tricarboxylic acid. It was found that DHIC-derived monomer units comprise only approx. 10% of enzymically prepared dopa-melanins but as much as a half of intact, natural eumelanins. The results also show that dopa-melanins prepared at higher pH retain higher percentages of the carboxyl group of dopa and contain higher percentages of pyrrole units, and that melanins are decomposed to a significant extent on acid treatment, the method commonly used to isolate melanins from natural sources. PMID- 3089299 TI - Biochemical studies on a 12-lipoxygenase in human uterine cervix. AB - Human uterine cervix possesses a high 12-lipoxygenase activity; this enzyme has been isolated in a purified form from the squamous epithelial region of human cervix and its major properties have been investigated. Enzyme activity was present in all subcellular fractions obtained by centrifugation; the highest specific activity was associated with the microsome fraction (160,000 X g pellet). Purification of the enzyme was achieved by acetone precipitation, ion exchange chromatography on CM-cellulose and affinity chromatography on linoleyl aminoethyl-Sepharose. The product from the incubation of sodium [1 14C]arachidonate with crude enzyme extracts co-chromatographed with authentic 12 hydroxyeicosatetraenoic acid, but the purified enzyme gave a product that behaved like the 12-hydroperoxy derivative. The enzyme had optimum activity at pH 6.5, a Km of 15 microM for arachidonic acid and was stimulated by ATP and Ca2+. Enzyme activity was inhibited by esculetin, nordihydroguaiaretic acid, eicosatetraynoic acid, detergents at concentrations greater than 0.1% (w/v) and preincubation of substrate with GSH and GSH peroxidase. The occurrence of a high 12-lipoxygenase activity is discussed in relation to the specific physiological functions of this tissue. PMID- 3089300 TI - Inhibition of CO2 production from aminopyrine or methanol by cyanamide or crotonaldehyde and the role of mitochondrial aldehyde dehydrogenase in formaldehyde oxidation. AB - Previous results have shown that cyanamide or crotonaldehyde are effective inhibitors of the oxidation of formaldehyde by the low-Km mitochondrial aldehyde dehydrogenase, but do not affect the activity of the glutathione-dependent formaldehyde dehydrogenase. These compounds were used to evaluate the enzyme pathways responsible for the oxidation of formaldehyde generated during the metabolism of aminopyrine or methanol by isolated hepatocytes. Both cyanamide and crotonaldehyde inhibited the production of 14CO2 from 14C-labeled aminopyrine by 30-40%. These agents caused an accumulation of formaldehyde which was identical to the loss in CO2 production, indicating that the inhibition of CO2 production reflected an inhibition of formaldehyde oxidation. The oxidation of methanol was stimulated by the addition of glyoxylic acid, which increases the rate of H2O2 generation. Crotonaldehyde inhibited CO2 production from methanol, but caused a corresponding increase in formaldehyde accumulation. The partial sensitivity of CO2 production to inhibition by cyanamide or crotonaldehyde suggests that both the mitochondrial aldehyde dehydrogenase and formaldehyde dehydrogenase contribute towards the metabolism of formaldehyde which is generated from mixed function oxidase activity or from methanol, just as both enzyme systems contribute towards the metabolism of exogenously added formaldehyde. PMID- 3089302 TI - Molecular biology of hydrogenases. Szeged (Hungary)--15-20 September 1985. PMID- 3089301 TI - Cell surface glycosaminoglycans of rat rhabdomyosarcoma lines with different metastatic potentials and of non-malignant rat myoblasts. AB - Glycosaminoglycans of cultured nickel-induced rat rhabdomyosarcoma cell lines with different metastatic potentials and of non-malignant myoblasts, grown in the presence or in the absence of hydrocortisone, were studied comparatively. The newly formed [3H]glucosamine-labelled cell surface proteoglycans and glycosaminoglycans were separated by ion exchange chromatography and partially characterized. The overall incorporation of the label in the glycosaminoglycan fractions and the average molecular weight of the heparan and of the chondroitin sulfate proteoglycans was lower in the malignant cells than in the non-malignant L6 myoblasts. The strongly metastatic 9-4/0 parental line and the 6 subline were relatively richer in chondroitin sulfate and poorer in dermatan sulfate labels than the very weakly metastatic 8 subline and the L6 myoblasts. Hyaluronic acid and heparan sulfate labels were inversely related to the metastatic capacity of the cell lines studied. Hydrocortisone treatment induced an increase in the cell surface chondroitin and dermatan sulfate labels in the case of the strongly metastatic lines, and a decrease of the same parameters in the case of the weakly metastatic 8 line. PMID- 3089303 TI - Investigation of the H2-oxidizing activities of Alcaligenes eutrophus H16 membranes with artificial electron acceptors, respiratory inhibitors and redox spectroscopic procedures. AB - Membrane particles, prepared from cells of Alcaligenes eutrophus H16 by lysozyme treatment and 100 000 X g centrifugation, catalyzed a H2-dependent reduction of methylene blue, menadione, 2,6-dichlorophenol-indophenol (DCPIP), and O2. While the reaction with methylene blue was not altered by 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), the H2-dependent reductions of menadione, DCPIP and O2 were strongly inhibited, indicating that in these reaction components of the respiratory chain other than the membrane-bound hydrogenase were involved. The effect of pentane extraction of membranes on the H2-dependent reductions of methylene blue and menadione were different from those of DCPIP and O2. This suggested that ubiquinone might not be involved in the pathway of the electrons from H2 to methylene blue or menadione, while it might be involved in the pathway to DCPIP and O2. Because the H2-dependent reduction of menadione is sensitive to HQNO, it follows that HQNO might bind to a site upstream of ubiquinone. Further evidence for this hypothesis came from a new technique to record UV and visible redox-difference spectra of membranes under the conditions of a steady-state electron flow. HQNO did not increase the reduction level of ubiquinone relative to the cytochromes. Neither HQNO nor menadione had any influence on the redox difference patterns of the cytochromes as determined with low temperature and room temperature spectroscopy. PMID- 3089304 TI - The use of nickel to probe the role of hydrogen metabolism in cyanobacterial nitrogen fixation. AB - The hydrogenase activities of the heterocystous cyanobacteria Anabaena cylindrica and Mastigocladus laminosus are nickel dependent, based on their inability to consume hydrogen with various electron acceptors or produce hydrogen with dithionite-reduced methyl viologen, after growth in nickel-depleted medium. Upon addition of nickel ions to nickel-deficient cultures of A. cylindrica, the hydrogenase activity recovered in a manner which was protein synthesis-dependent, the recovery being inhibited by chloramphenicol. We have used the nickel dependence of the hydrogenase as a probe of the possible roles of H2 consumption in enhancing nitrogen fixation, and particularly for protecting nitrogenase against oxygen inhibition. Although at the usual growth temperatures (25 degrees for A. cylindrica and 40 degrees for M. laminosus), the cells consume H2 vigorously in an oxyhydrogen reaction after growth in the presence of nickel ions, we have not found that the reaction confers any significant additional protection of nitrogenase, either at aerobic pO2 (for both organisms) or at elevated pO2 (for A. cylindrica). However, at elevated temperatures (e.g., 40 degrees for A. cylindrica and 48 degrees for M. laminosus) a definite protective effect was observed. At these temperatures both organisms rapidly lost acetylene reduction activity under aerobic conditions. When hydrogen gas (10%) was present, the cells retained approximately 50% of the nitrogenase activity observed under anaerobic conditions (argon gas phase). No such protection by hydrogen gas was observed with nickel-deficient cells. Studies with cell-free extracts of A. cylindrica showed that the predominant effect of temperature was not due to thermal inactivation of nitrogenase. PMID- 3089305 TI - Hydrogenase activities in cyanobacteria. AB - In the unicellular Anacystis nidulans, the expression of both the H2-uptake (with phenazine methosulfate or methylene blue as the electron acceptor) and H2 evolution (with methyl viologen reduced by Na2S2O4) was dependent on Ni in the culture medium. In extracts from Anacystis and Anabaena 7119, H2-evolution and uptake activities were strongly inhibited by Cu2+, p-chloromercuribenzoate and HgCl2 suggesting that at least one functional SH-group is involved in catalysis by hydrogenase. Extracts from the N2-fixing Anabaena 7119 contained two different hydrogenase fractions which could be separated by chromatography on DE-52 cellulose using a linear NaCl concentration gradient. The fraction eluting with 0.13 M NaCl from the column catalyzed only the uptake of H2 with methylene blue as the electron acceptor but virtually not the evolution of H2 ("uptake" hydrogenase fraction). The fraction eluting at a NaCl strength of 0.195 M catalyzed both H2-uptake with methylene blue and H2-evolution with reduced methyl viologen ("reversible" hydrogenase fraction). Growth under anaerobic conditions drastically enhanced the activity levels of the "reversible" but not of the "uptake" hydrogenase fraction. The "uptake" hydrogenase but not the "reversible" protein was activated by reduced thioredoxin. It is suggested that thioredoxin activates the H2-uptake by the membrane-bound "uptake" hydrogenase also in intact cells. The occurrence of the number of hydrogenases in cyanobacteria will be reevaluated. PMID- 3089306 TI - Genetics of hydrogenase from aerobic lithoautotrophic bacteria. AB - Aerobic facultatively autotrophic hydrogen bacteria are distinguished on the basis of their hydrogen-oxidizing enzyme system (Hox). The major group, represented by Paracoccus denitrificans and Pseudomonas facilis, contains a membrane-bound, electron transport-coupled protein. Species of Nocardia are characterized by the possession of a cytoplasmic NAD-dependent hydrogenase. Both enzymes are present in strains of Alcaligenes. All hydrogenases from lithoautotrophs are H2-consuming nickel-iron-sulfur proteins. Despite these common characteristics, hydrogenases differ in catalytic and molecular properties, in particular in the regulation of enzyme synthesis. Hydrogenase formation is either inducible by H2 (e.g. P. denitrificans strain F1, Alcaligenes hydrogenophilus) or subject to derepression in response to the supply of reductant, temperature, and oxygen (e.g. Alcaligenes eutrophus). The only plasmid encoded Hox function has been conclusively identified in species of Alcaligenes. Structural and regulatory hox genes reside on megaplasmids, ranging in size between 400 and 500 kilobase pairs (kb). Most of the plasmids are self transmissible by conjugation. Hox genes of A. eutrophus H16 have been localized by plasmid curing, genetic transfer, molecular cloning and analysis of plasmid deletions and insertions. They seem to be clustered in a DNA sequence of approximately 50 kb, representing several transcriptional units. In addition, a chromosomally encoded regulatory function is required for the expression of plasmid-linked hox genes. Plasmid pHGl of A. eutrophus H16 has been transferred to the non-lithoautotrophic soil bacterium JMP222. Both hydrogenases are expressed in the new host. The current state of hydrogenase genetics in Alcaligenes is discussed in reference to hydrogenase systems of other lithoautotrophic bacteria. PMID- 3089307 TI - Characterization of a native subunit of the NAD-linked hydrogenase isolated from a mutant of Alcaligenes eutrophus H16. AB - The cytoplasmic, NAD-linked hydrogenase of Alcaligenes eutrophus H16 consists of four non-identical subunits. From the mutant strain HF14, defective in this enzyme, a protein was isolated that reacted with specific antibodies raised against the wild-type hydrogenase; the reaction type was of partial identity. The same protein was also tested with specific antibodies raised against each of the four denatured subunits of the wild-type hydrogenase and was found to be completely identical with the second largest subunit; it reacted weakly with the antibody against the largest subunit and not at all with the antibody against the small subunits. In SDS-polyacrylamide gel electrophoresis the protein of the mutant migrated as a single polypeptide and corresponded to the second largest subunit of soluble hydrogenase with Mr = 56,000. The mutant enzyme strongly differed from the wild-type hydrogenase in its binding behaviour to chromatographic gels. It had pronounced hydrophobic properties and bound strongly to phenyl-Sepharose; it had high affinity to triazin dye gels. Enzymatically the polypeptide was totally inactive with NAD as electron acceptor, but showed weak residual activities with methylene blue, ferricyanide and cytochrome c. The protein also contained nickel; however, because of the instability of this polypeptide the amount varied between 0.2-1.4 nickel per enzyme molecule. As shown by ESR studies, the iron is organized in a [4Fe-4S] cluster but is partially present also in the 3Fe-form. No nickel signal could be detected. The role of the polypeptide subunit for hydrogen activation in the intact hydrogenase is discussed. PMID- 3089308 TI - Genetic and physiological characterization of new Escherichia coli mutants impaired in hydrogenase activity. AB - The Mu dl (ApR lac) bacteriophage was used to generate mutants of Escherichia coli which were defective in formate hydrogenlyase. Three mutants were chosen for further analysis: they lacked hydrogenase (hydrogen: benzyl viologen oxidoreductase) activity, but produced normal levels of fumarate reductase activity and two- to three-fold reduced levels of benzyl viologen (BV)-dependent formate dehydrogenase activity. Two of them (hydC) were shown to contain about 4 fold reduced amounts of formate hydrogenlyase and fumarate-dependent H2 uptake activities. The third one (hydD) was totally devoid of both activities. Their insertion sites were located at 77 min on the E. coli map. Subdivision of these mutants into two classes was subsequently based on the restoration capacity of hydrogenase activity with high concentration of nickel in the growth media. Addition of 500 microM NiCl2 led to a complete recovery of hydrogenase activity, and to the concomitant restoration of normal BV-linked formate dehydrogenase, formate hydrogenlyase and fumarate-dependent H2 uptake activities in the hydC mutants. The hydD mutant was insensitive to the effect of nickel. Expression of the lac operon in hydC and hydD mutants was induced by anaerobiosis. It was not increased by the addition of formate under anaerobic conditions. The presence of nitrate resulted in slightly reduced beta-galactosidase activities in the hydC mutants, whereas those found in the hydD mutant reached only one third of the level obtained in its absence. Fumarate had no effect on both classes. Moreover, in contrast to the hydD locus, the hydC::Mu dl fusions were found to be dependent upon the positive control exerted by the nirR gene product and were totally repressed by an excess of nickel. In addition, the low levels of overall hydrogenase-dependent activities found in a nirR strain were also relieved by the presence of nickel. Our results strongly suggest that the pleiotropic regulatory gene nirR is essential for the expression of a gene (hydC) involved in either transport or processing of nickel in the cell, whose alteration leads to a loss of hydrogenase activity. PMID- 3089309 TI - Hydrogen evolution from dithionite and H2 photoproduction by hydrogenase incorporated into various hydrophobic matrices. AB - The effects of surfactants, lipids and amphiphilic viologen mediators on H2 production from dithionite as well as on Ru(bpy) sensitized H2 photoproduction by hydrogenase from Thiocapsa roseopersicina was studied. Three systems which differed as to the nature of the hydrophobic matrix around the hydrogenase were tested. An enhanced hydrogenase activity was observed in the presence of surfactants, in the 1-6 mM concentration range. Hydrogenase showed a selectivity for the amphiphilic viologens, 2C7-diCl was the most efficient electron mediator in both reactions. H2 photoproduction seemed not to be feasible in the detergent hydrogenase system because of intensive foaming. Hydrogenase incorporated into liposomes catalyzed H2 photoevolution efficiently but the rate was decreasing in time, though reversibly. Using intact bacterial cells instead of purified hydrogenase yielded stable H2 photoevolution for at least 12 hours. This system offers several advantages for potential practical applications. PMID- 3089310 TI - Light induced H2 evolution in a hydrogenase-TiO2 particle system by direct electron transfer or via rhodium complexes. AB - Three different hydrogenases (isolated from Clostridium pasteurianum, Desulfovibrio desulfuricans strain Norway 4 and D. baculatus 9974) added to a suspension of TiO2 (anatase) powder are able to catalyze H2 evolution under band gap illumination of the semiconducting particles, and in the presence of EDTA or methanol as electron donor. This H2 production can be obtained by the direct electron transfer from the conduction band of the TiO2 particles to the active site of the enzyme at pHs higher than 7. This mediator-independent charge transfer is more efficient with C. pasteurianum and D. baculatus 9974 hydrogenases, and in the presence of methanol. Rhodium tris- and bis-bipyridyl complexes can act efficiently as electron carriers from the supporting particles to the adsorbed enzyme molecules in cases where the direct transfer is inefficient. PMID- 3089311 TI - [Interactions between the progesterone receptor of the chicken oviduct and the heat shock protein hsp90]. PMID- 3089312 TI - Purification to homogeneity of Azotobacter vinelandii hydrogenase: a nickel and iron containing alpha beta dimer. AB - Azotobacter vinelandii hydrogenase has been purified to homogeneity from membranes. The enzyme was solubilized with Triton X-100 followed by ammonium sulfate-hexane extractions to remove lipids and detergent. The enzyme was then purified by carboxymethyl-Sepharose and octyl-Sepharose column chromatography. All purification steps were performed under anaerobic conditions in the presence of dithionite and dithiothreitol. The enzyme was purified 143-fold from membranes to a specific activity of 124 mumol of H2 uptake . min-1 . mg protein-1. Nondenaturing polyacrylamide gel electrophoresis of the hydrogenase revealed a single band which stained for both activity and protein. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed two bands corresponding to peptides of 67,000 and 31,000 daltons. Densitometric scans of the SDS-gel indicated a molar ratio of the two bands of 1.07 +/- 0.05. The molecular weight of the native enzyme was determined by three different methods. While gel permeation gave a molecular weight of 53,000, sucrose density gradient centrifugation and native polyacrylamide gel electrophoresis gave molecular weights of 98,600 +/- 10,000 and 98,600 +/- 2,000, respectively. We conclude that the A. vinelandii hydrogenase is an alpha beta dimer (98,000 daltons) with subunits of 67,000 and 31,000 daltons. Analyses for nickel and iron indicated 0.68 +/- 0.01 mol Ni/mol hydrogenase and 6.6 +/- 0.5 mol Fe/mol hydrogenase. The isoelectric point of the enzyme was 6.1 +/- 0.01. In addition, several catalytic properties of the enzyme have been examined. The Km for H2 was 0.86 microM, and H2 evolution was observed in the presence of reduced methyl viologen. The pH profile of enzyme activity with methylene blue as the electron acceptor has been determined, along with the Km and Vmax for various electron acceptors. PMID- 3089313 TI - Differential inhibition of catalytic sites in Desulfovibrio gigas hydrogenase. AB - The hydrogenase of Desulfovibrio gigas has been shown to contain one nickel atom, a cluster with three irons and two clusters of the [4Fe-4S] type in an 89 kDa molecule. Though evidence that the nickel ion is involved in the site of hydrogen activation has been presented for this and other hydrogenases, the role of nickel and of the other redox centres in the protein remains to be firmly identified. We have examined the effects of inhibitors of hydrogenase activity in an attempt to identify the functions of the prosthetic redox centres. We have shown carbon monoxide to inhibit at the site of hydrogen activation. The dye, procion red, was found to compete with electron acceptors at a different site, and partial denaturation with the detergent lithium dodecyl sulphate resulted in the differential inhibition of hydrogen activation and substrate reduction. These results imply the presence of distinct domains within the protein with different catalytic activities. PMID- 3089314 TI - Isolation and immunological characterization of the four non-identical subunits of the soluble NAD-linked hydrogenase from Alcaligenes eutrophus H16. AB - The soluble NAD-linked hydrogenase of Alcaligenes eutrophus H16 is a tetramer consisting of 4 non-identical subunits with molecular weights of 63,000, 56,000, 30,000 and 26,000. Conditions have been elaborated to separate and isolate each of these subunits as a single polypeptide by a preparative scale of polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate (SDS). Against each of the 4 subunits, polyclonal antibodies were produced. From the crude sera isolated from rabbits, the antibodies (IgG fractions) were purified by Protein A-Sepharose chromatography. By the double immunodiffusion method, comparison of the 4 types of subunits revealed that they are in fact different polypeptides. Subunit 1 (Mr = 63,000) and subunit 2 (Mr = 56,000) only reacted with their own specific antibodies and showed no cross-reaction whatsoever with the antibodies raised against the other subunits. The only immunological relationship among the different subunits was observed with subunit 3 (Mr = 30,000) and subunit 4 (Mr = 26,000); the type of cross-reaction indicated that they are partially identical. A. eutrophus H16 contains, in addition to the soluble hydrogenase, a membrane-bound hydrogenase which is a dimer composed of 2 subunits with Mr of 61,000 and 30,000. Whereas the 2 native enzymes did not show any immunological cross-reaction with the respective antibodies, it was demonstrated by double immunofluorescence labeling on nitrocellulose filters that the larger subunit of the membrane-bound hydrogenase cross-reacted significantly with the antibodies raised against subunit 2 of the soluble hydrogenase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089315 TI - NAD+-dependent hydrogenase from the hydrogen oxidizing bacterium Alcaligenes eutrophus Z1. Stabilization against temperature and urea induced inactivation. AB - Chemical modification of the NAD+-dependent hydrogenase from the hydrogen oxidizing bacterium Alcaligenes eutrophus Z1 results in considerable enzyme stabilization towards urea and temperature induced inactivation. The stabilizing effect was shown to originate from the suppression of hydrogenase tetramer dissociation. The magnitudes of the stabilizing effects (5-fold and more) were in agreement with the values predicted on the basis of the enzyme thermoinactivation mechanism postulated earlier. Hydrophobic interactions are considered to be critical for the stability of the enzyme quaternary structure. Various methods of hydrogenase immobilization were tested. The enzyme was immobilized with a high retention of activity on aminated silochrom via its carboxylic groups. PMID- 3089316 TI - Protein structural changes associated with active and inactive states of hydrogenase from Thiocapsa roseopersicina. AB - Electrophoretic and isoelectrofocusing behavior of the hydrogenase from Thiocapsa roseopersicina under various conditions revealed remarkable properties of this enzyme: there are two active forms which differ in their molecular masses as well as in oxygen sensitivity; the apparent molecular masses of the active hydrogenase forms (90 and 49 kDa) differ considerably from those in the inactive state (64, 34, and 15 kDa); the active forms and some of the inactivated ones can be transformed into each other reversibly; urea can unfold the 64 and 34 kDa proteins but not the 49 kDa form at room temperature; the pI of these proteins are different in the presence of urea. The results suggest large rearrangements in the hydrogenase protein structure which are associated with the enzymatically active and inactive states. It is concluded that reversible formation of disulfide bonds cannot be the major cause for maintaining the enzyme conformation. Strong hydrophobic interactions are suggested to be primarily responsible for the structural stability and for the rearrangements. PMID- 3089317 TI - Mechanism of pancreatic adaptation to diet. PMID- 3089318 TI - Counting cycles of EF-Tu to measure proofreading in translation. AB - A new method (T. Ruusala et al., 1982, EMBO J. 1, 75-78, 741-748) for analyzing kinetic proofreading in translation is described. An in vitro system is arranged so that its rate of polypeptide synthesis is determined by the release rate of GDP from EF-Tu in the absence of EF-Ts. This enables the counting of the number of EF-Tu cycles for correct as well as for incorrect peptide bonds. The necessary equations are derived and the approximations involved in these are discussed together with data from experiments not previously described. PMID- 3089319 TI - A quantitative dynamic concept of the interphase partition of lipids: application to bile salt-lecithin-cholesterol mixed micelles. AB - A system is proposed for a quantitative classification of lipids, based on interphase partition coefficients. This system enables calculation of exchanges of lipid molecules between phases. The mass/volume chemical unit mol X cm-3, strictly derived from the CGS system, is used, thus simplifying mathematical relations. Applied to bile salt-lecithin-cholesterol mixed micelles, this dynamic concept gives new insight into the variations of physico-chemical parameters. Experimental results obtained with the glycodesoxycholate and the taurocholate show a striking difference in partition coefficients between aqueous and mixed bile salt-lecithin interfacial phases. A new model applying triangular co ordinates to a bile salt-lecithin-cholesterol mixed lipid phase is described. PMID- 3089320 TI - [Heterogeneity of ciguatoxins extracted from fish caught in the French Antilles]. AB - Ciguatoxin-like substances were extracted from the viscera or the flesh of eight Caribbean fish species, including small invertebrate feeders and large carnivores. The had similar properties, i.e. pharmacological action, solubility, chromatographic behaviour on silicic acid or Sephadex LH 20 column, stability in a weak acid solution and instability in alkaline medium. However, Florisil column and thin-layer chromatography showed different ciguatoxins whose number depended on tissue or species but not on fish trophic level. Less polar ciguatoxins appeared in salted and dried flesh. Thus, fish ciguatoxins are believed to be closely related substances, possibly changing in structure according to particular experimental conditions. PMID- 3089321 TI - Partial purification and some kinetic properties of glucose-6-phosphate dehydrogenase from Phycomyces blakesleeanus. AB - Glucose-6-phosphate dehydrogenase from sporangiophores of Phycomyces blakesleeanus NRRL 1555 (-) was partially purified. The enzyme showed a molecular weight of 85 700 as determined by gel-filtration. NADP+ protected the enzyme from inactivation. Magnesium ions did not affect the enzyme activity. Glucose-6 phosphate dehydrogenase was specific for NADP+ as coenzyme. The reaction rates were hyperbolic functions of substrate and coenzyme concentrations. The Km values for NADP+ and glucose 6-phosphate were 39.8 and 154.4 microM, respectively. The kinetic patterns, with respect to coenzyme and substrate, indicated a sequential mechanism. NADPH was a competitive inhibitor with respect to NADP+ (Ki = 45.5 microM) and a non-competitive inhibitor with respect to glucose 6-phosphate. ATP inhibited the activity of glucose-6-phosphate dehydrogenase. The inhibition was of the linear-mixed type with respect to NADP+, the dissociation constant of the enzyme-ATP complex being 2.6 mM, and the enzyme-NADP+-ATP dissociation constant 12.8 mM. PMID- 3089322 TI - Influence of whole-body gamma-irradiation upon rat erythrocyte: lipid peroxidation and osmotic fragility. AB - The effects of whole-body gamma-irradiation of rats (8 Gy) on erythrocyte enzymes and biochemical components involved in lipid peroxidation were studied. Decreased superoxide dismutase and glutathione reductase activities, and lowered concentrations of reduced glutathione, were found to be the main factors responsible for the observed increase in lipid peroxidation in the erythrocytes of irradiated rats. This increased lipid peroxidation did not result in a greater tendency to hemolysis in hypotonic media; on the contrary, the mean osmotic fragility was decreased at days D + 1 and D + 3 after irradiation. The behavior of the erythrocyte populations towards hemolysis in hypotonic media appeared to be most homogeneous at days D + 4 and D + 8 after irradiation, which correspond to maxima of malonic dialdehyde concentrations in erythrocytes. Such a synchrony of variations suggests that crosslinking of primary amino groups of proteins or phospholipids by malonic dialdehyde might produce a rigidification in erythrocyte membranes, possibly leading to a more homogeneous behavior of the erythrocyte populations towards hemolysis in hypotonic media. PMID- 3089323 TI - The primary structure of wheat germ tRNAArg--the substrate for arginyl tRNAArg:protein transferase. AB - Besides its major role in protein synthesis, wheat germ arginyl-tRNAArg can serve as an amino acid donor in an enzymatic reaction to bovine serum albumin catalysed by the enzyme arginyl-tRNAArg: protein transferase. The nucleotide sequence of the tRNAArg involved in this reaction was determined to be: pG-A-C-U-C-C-G-U-m1G m2G-C-C-C-A-A-D-Gm-G-A-X-A-A-G-G-C-m2(2) G-C-U-G-G-U-Cm-U-I-C-G-m2A-A-A-C-C-A-G-A G-A-D-U-m5C-U-G-G-G-T-psi -C-G-m1 A-U-C-C-C-C-A-G-C-G-G-A-G-U-C-G-C-C-AOH. We suggest that the decapentanucleotide 5'-G-U-Pu-m2G-C-N-C-A-A-D-Gm-G-A-X-A-3', localized in the D-region, interacts specifically with the protein transferase. PMID- 3089324 TI - The primary structure of threonine tRNA (anticodon I-G-U) from bovine liver. AB - The primary structure of threonine tRNA (anticodon I-G-U) from bovine liver has been determined using 32P postlabeling methods. Its nucleotide sequence is pG-G-C C-C-U-G-U-m1G-m2G-C-U-A-G-C-D-G-G-D-C-A-A-A-G-C-m2(2)G-C-C- U-G-U-m3 C-U-I-G-U t6A-A-A-C-A-G-G-A-G-A-D-m5C-C-U-G-G-G-U-psi-C-G-m1 A-A-U-C-C-C-A-G-C-G-G-G-G-C m5C-U-C-C-A. The anticodon I-G-U, according to the wobble hypothesis, is expected to recognize A-C-U, A-C-C and A-C-A, 3 out of the 4 codons for threonine. However, if the original wobble hypothesis, as it has been shown recently for several yeasts and a fungus, is only restricted to U and C in the ox, it would recognize only 2 codons: A-C-C and A-C-U. PMID- 3089325 TI - Structure of gastrointestinal mucins: searching for the Rosetta stone. PMID- 3089326 TI - Some important concepts in the current theories of electron transfer in biological systems. AB - The main concepts pertinent to the current theories of electron transfer in biological systems are briefly presented. The different models used to evaluate the purely electronic factors of the transfer are reviewed. PMID- 3089327 TI - Further characterization of the light breast cyst fluid protein, GCDFP-15. AB - A light protein of breast cyst fluid from women with gross cystic disease, termed GCDFP-15 in the literature, has been investigated. This light protein was purified by preparative electrophoresis on sodium dodecyl sulfate polyacrylamide gel. Its isoelectric point has been determined as 3.75 and its molecular weight has been estimated at 17 400. The light protein was a glycoprotein containing about 163 amino acid residues; the glucidic fraction corresponded to 11% of the molecular weight. The N-terminal amino acid was blocked and the C-terminal amino acid was determined as valine. Antisera raised against this light protein have proved to be specific. In the literature, there is evidence suggesting that apocrine secretion is of prime importance in conditioning the biochemical composition of breast cyst fluid. Further information is needed to substantiate the hypothesis that in gross cystic disease the apocrine epithelium itself or some of its functional aspects are associated with the risk of neoplasia. The physicochemical characterization of the breast cyst fluid protein can contribute to the study of its biosynthesis and provide a better understanding of the physiopathology of gross cystic disease and its relationship to breast carcinoma. PMID- 3089328 TI - Purification and characterization of minor brain proteolipids: use of fast atom bombardment-mass spectrometry for peptide sequencing. AB - A combination of lipophilic gel permeation chromatography and ion-exchange chromatography in organic solvents was used to purify low molecular weight proteolipids from bovine brain. Cleavage peptides were purified by HPLC and studied mainly by the fast atom bombardment--mass spectrometry technique. A proteolipid of Mr 14 000 contains several peptides from the first 113 amino acids of the major myelin proteolipid (MMPL) plus an extra unknown blocked N-terminal peptide. A proteolipid of Mr 16 000 contains smaller peptides belonging to a C terminal fragment of MMPL of about 160 residues. These two proteolipids do not seem to be artifacts from MMPL. PMID- 3089329 TI - Functional interactions between mutated forms of ribosomal proteins S4, S5 and S12. AB - Here we show that ram mutations, either in ribosomal protein S4 or S5, decrease the proofreading flows for both cognate and noncognate ternary complexes bound by streptomycin-dependent (SmD) ribosomes. This effect is accompanied by a slight increase in the overall error frequency. More important, however, is the decreased proofreading of the cognate species which is almost reduced to wild type levels. The data suggest that it may be the reduction of the proofreading of the cognate substrate that is important for suppressing streptomycin dependence. Furthermore, we show that rpsE mutants, selected from streptomycin-dependent strains, behave kinetically very similarly to the previously described rpsD mutants. PMID- 3089331 TI - Kinetic properties of 5-carboxymethyl-2-hydroxymuconate semialdehyde dehydrogenase from Escherichia coli. AB - Kinetic properties of purified 5-carboxymethyl-2-hydroxymuconate semialdehyde (CHMSA) dehydrogenase (EC 1.2.1.-) in the 4-hydroxyphenylacetate meta-cleavage pathway from Escherichia coli have been studied. The temperature--activity relationship for the enzyme from 27 to 45 degrees C showed an Arrhenius plot with an inflexion at 36 degrees C. When 5-carboxymethyl-2-hydroxymuconic semialdehyde and NAD were used as variable substrates, the double reciprocal plots were all linear and the lines intersected at one point below the horizontal axis, suggesting that a sequential mechanism is operating. From the replots of intercepts and slopes against reciprocal substrate concentrations were calculated Km (CHMSA) = 9.0 +/- 1.02 microM, Km (NAD) = 29.1 +/- 4.65 microM and the value for the dissociation constant of enzyme--NAD complex = 6.3 +/- 1.21 microM. ATP and the product of the reaction (NADH) acted as competitive inhibitors of the enzyme with respect to NAD. Apparent Ki values, estimated from Dixon plots, were 25.0 +/- 3.5 and 88.0 +/- 22.1 microM for NADH and ATP, respectively. PMID- 3089330 TI - Thiolation of low-density lipoproteins and their interaction with L2C leukemic lymphocytes. AB - We present here, a new method for coupling sulfhydryl groups (SH) to low-density lipoprotein (LDL) surface. This method uses homocysteine thiolactone (HCTL) which reacts with lysine residues in a very mild manner, and permits the selection of the number of SH bound per LDL. Under our experimental conditions (8 SH/LDL), the affinity of thiolated LDL for the specific receptors and their further internalization by L2C lymphocytes are preserved. PMID- 3089332 TI - Thermal stability of the Z conformation of the hexanucleoside pentaphosphate d(br5CGbr5CGbr5CG): evidence for a conformational transition before melting. AB - The thermal stability of the hexanucleoside pentaphosphate d(br5CGbr5CGbr5CG) has been studied at two nucleotide concentrations, in the presence of 1 M NaClO4. At low nucleotide concentration (7 X 10(-5) M), circular dichroism experiments show a conformational transition from the Z conformation to another conformation, named X, which is not the B conformation, as the temperature is increased from 0 to 35 degrees C. Between 40 and 65 degrees C, another transition is observed which corresponds to the melting of the X conformation. At higher nucleotide concentration (2 X 10(-3) M), circular dichroism and 31P nuclear magnetic resonance experiments show that at low temperature (br5dC-dG)3 adopts the Z conformation. There are associations between the oligonucleotides which progressively disappear as the temperature increases. In the range 35-60 degrees C a transition from the Z conformation to another conformation is observed. This new conformation is the X conformation detected at low nucleotide concentration. PMID- 3089334 TI - [Inhibitory effect of pertussis toxin on the metabolism of guanine nucleotides in transducin from bovine outer rod segments]. AB - Transducin from bovine retinal rod outer segments possesses two sites responsible for the binding of guanyl nucleotides, one of which is specific only for GTP (GTP site), while the other one may bind both GTP and GDP (GTP/GDP-site). Pertussis toxin covalently modifies the alpha-subunit of transducin as a result of which 83% of GDP bound at the GTP/GDP site of the protein remain tightly bound and are not displaced by Gpp(NH)p excess. The GTP-site in modified transducin binds Gpp(NH)p at the same rate and reveals the same sensitivity to rhodopsin as does native transducin. Presumably, the GTP/GDP site is localized in the alpha-subunit of transducin. The inhibiting effect of pertussis toxin on GTP hydrolysis by transducin and on stimulation of retinal rod outer segment phosphodiesterase by guanyl nucleotides is due to the tight binding of GDP in the active center of the protein after transducin ADP-ribosylation, which makes impossible the formation of a complex between GTP and the alpha-subunit of transducin. PMID- 3089333 TI - [Isolation of the hexameric form of purine nucleoside phosphorylase from E. coli. Comparative study of trimeric and hexameric forms of the enzyme]. AB - The presence of two forms (high and low molecular weight ones) of purine nucleoside phosphorylase II (purine nucleoside: orthophosphate ribosyltransferase, EC 2.4.2.1) was demonstrated. The high molecular weight form of the enzyme was purified, and the properties of both forms were compared. The enzyme forms were shown to differ in their quaternary structure (trimeric and hexameric), molecular weight of the native enzyme and its subunits (85,000 and 28,000 for the trimer, 150,000 and 25,000 for the hexamer, respectively) as well as substrate specificity (the trimer is specific for all major purine nucleosides, while the hexamer does not cleave adenine nucleosides). Adenosine is a competitive inhibitor of the hexameric form with respect to deoxyguanosine (Ki = 1.16 X 10(-3) M); the Km value for deoxyguanosine is 9.85 X 10(-5) M. The isoelectric point for the both forms of the enzyme in the presence of 9 M urea is about 5.5. Both forms have a pH optimum of phosphorolytic activity between 6.5 and 7.0. PMID- 3089336 TI - Neurotoxicity induced by combined lithium-thioridazine treatment. PMID- 3089335 TI - [Effect of a hypertonic mannitol solution on the peri-infarct area of an isolated frog heart]. AB - The influence of the hypertonic (3%) solution of mannitol on the process of the excitability recovery (in the near necrotic zone) appeared as a result of the necroses tissue effect on the ventricle has been investigated in the experiments on the isolated frog's heart. The analogous perfusion was conducted by Ringer solution in the control experiments. The process of isopotential phase S-T recovery was practically the same at heart perfusion with Ringer solution or with mannitol. Simultaneous registration of ventricular mechanogram showed the pronounced negative inotropic effect of mannitol. It is suggested that the positive effect of mannitol which has been noted under clinic conditions during the treatment of ischemic disease, doesn't connect with the effect of hypertonic solution on the cells excitability of periinfarcted (near necrotic) zone. PMID- 3089337 TI - Analysis of amniotic fluid proteins by isoelectrofocusing (IEF) in pregnancies complicated by polyhydramnios and Rh-sensitization. AB - Among the most recent methods for investigation of proteins in biological fluids SDS polyacrilamide-gel-electrophoresis (SDS-PAGE) and isoelectrofocusing (IEF) have recently been introduced into laboratory practice. The present investigation was performed on 14 samples of amniotic fluid obtained during the third trimester in pregnancies complicated by Rh-sensitization and polyhydramnios in which protein concentration was higher than in normal pregnancies. The obtained results suggest that IEF analysis seems to have a selective advantage in allowing the separation of bands which cannot easily be recognized with SDS electrophoresis. These bands detected by IEF and present in amniotic fluid during late pregnancy seem to be related to some molecular weight lipoprotein fractions and we suggest that they might be used as a possible marker for monitoring fetal lung maturation. In conclusion we think that it would be of great interest to evaluate the usefulness of IEF analysis in examining amniotic fluid obtained during pregnancies complicated by polyhydramnios and Rh-sensitization. PMID- 3089338 TI - 2-bromo-alpha-ergocryptine mesylate (CB-154) inhibits prolactin and luteinizing hormone secretion in the prepubertal female rat. AB - Treatment of immature female rats with 100 micrograms 2-bromo-alpha-ergocryptine mesylate (CB-154) per ml drinking water beginning on Day 30 of age until vaginal opening delayed puberty by 6 days. Rats treated with CB-154 exhibited vaginal opening at 43.3 +/- 0.6 days whereas controls exhibited vaginal opening at 37.9 +/- 0.8 days. Most interestingly, serum levels of luteinizing hormone (LH) and prolactin (PRL) on Days 31-35, determined by a homologous radioimmunoassay were significantly lower in treated rats than in controls. The ovarian concentrations of progesterone (P) and androstenedione (A) were lower in rats treated with CB 154 than in controls; ovarian estradiol (E2) concentrations were low in both groups. Serum levels of P (but not A and E2) were reduced on Days 31-35 of the treatment period. Cessation of the CB-154 treatment on the morning of Day 35 returned the onset of puberty to normal values; steroid and gonadotropin levels also returned to normal values within 2 days after removal of the CB-154 from the drinking water. Near the time of onset of puberty, serum levels of LH in rats treated with CB-154 returned to control values. These data indicate that in the female rat the delay in puberty induced by CB-154 might be due to a reduction in the secretion of LH, especially since the onset of delayed puberty in rats treated with CB-154 correlates with an increase in the serum level of LH. Further studies are needed to elucidate the specific effects of hypoprolactinemia on ovarian function and the onset of puberty in the rat. PMID- 3089339 TI - Direct biphasic modulation of gonadotropin-stimulated testicular androgen biosynthesis by prolactin. AB - Prolactin (PRL) exerts both stimulatory and inhibitory effects upon testicular steroidogenesis in vivo. The direct effects of PRL on biosynthesis of testicular androgen were studied in primary cultures of testicular cells obtained from adult, hypophysectomized or neonatal, intact rats. In cells from adult animals, treatment with human chorionic gonadotropin (hCG) (10 ng/ml) significantly increased testosterone and progesterone production relative to their respective controls. In contrast, neither steroid was increased by treatment with rat PRL (rPRL) or ovine PRL (oPRL) alone. Upon addition of 0.1-3 ng/ml of either rPRL or oPRL to the hCG-treated cultures, testosterone production was progressively increased up to a maximum of 70% greater than with hCG alone. However, when PRL exceeded 3 ng/ml, the testosterone response began to decline and was 39 or 24% less than from cells treated with hCG alone at 300 ng/ml of rPRL or oPRL, respectively. A similar biphasic response pattern was observed in cells from neonatal animals. In contrast to the biphasic effect of PRL on production of androgen, PRL treatment enhanced hCG-stimulated production of progesterone in a dose-related manner without exerting an inhibitory effect. At 3 and 300 ng/ml, rPRL augmented hCG action by 2.5- and 8-fold, respectively. Similarly, in the presence of inhibitors of pregnenolone metabolism, rPRL also enhanced hCG stimulated production of pregnenolone. Quantitation of steroid intermediates in the testosterone biosynthetic pathway revealed that the stimulatory effect of 3 ng/ml rPRL on testosterone production was associated with 1.3- and 2.8-fold increases in accumulation of androstenedione and 17 alpha hydroxyprogesterone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089341 TI - Acrosomal status in fresh and capacitated human ejaculated sperm. AB - The acrosomal status of human sperm was evaluated by immunofluorescence utilizing a specific monoclonal antibody that recognizes target antigen(s) localized in the acrosomal cap region. Spontaneous acrosomal loss was first examined in sperm preparations used for successful in vitro fertilization of human eggs. In these sperm populations, less than 20% of the sperm underwent degenerative or spontaneous acrosomal loss following 24 h of incubation. The correlation of acrosomal loss with changes in motility and viability suggested that sperm senescence was not necessarily coupled to acrosomal loss. Chemical induction of acrosomal loss by calcium ionophore A23187 and lysophosphatidylcholine (LPC) was characterized. Maximal ionophore induction (10 microM A23187 in media containing calcium) was observed in cells exposed to capacitating conditions in vitro; sperm exposed to noncapacitating conditions did not readily acquire the ability to respond to ionophore. The reaction induced by ionophore was slow (60 min), and at least 30% of the cells were always resistant to induction. In contrast, LPC induced rapid, synchronous acrosomal loss in either freshly ejaculated or capacitated sperm in the presence or absence of extracellular calcium, suggesting that this loss was not a physiologic reaction. These studies may provide a basis for evaluating capacitation and ultimately fertility potential in the human male. PMID- 3089340 TI - Fat ablation and food restriction influence reproductive development and hibernation in ground squirrels. AB - The role of white adipose tissue in development of the reproductive apparatus of male golden-mantled ground squirrels was assessed by surgical removal of fat (lipectomy) immediately prior to onset of hibernation or by manipulation of fat levels through food restriction for 5 wk preceding hibernation. Animals then were maintained without food at 6 degrees C, and they hibernated from November 1983 until April 1984. At that time, blood plasma was assayed for hormone levels, and body mass, body composition, and masses of the testes and seminal vesicle prostate complex were determined. At autopsy, testes and sexual accessory organs were heavier in Control squirrels than in Food-Restricted or Lipectomized (LIPX) animals. Paired-testes mass was positively correlated with body mass. Testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were uniformly low in animals sampled during torpor, but were elevated in 2 animals that had regained the euthermic state. The Food-Restricted animals spent more time in torpor than did the other two groups, and the percentage of decrease in body mass over the hibernation season was less for Food-Restricted than for LIPX or Control animals. Adequate lipid stores may be essential for the normal development of the reproductive apparatus of male ground squirrels. In the field, animals with insufficient fat stores may forego reproduction and thereby conserve energy for survival. PMID- 3089342 TI - Ciliates from a fresh water sulfuretum. AB - Ciliates were collected from a freshwater sulfuretum, Lake Ciso, which is part of a gypsum karstic area whose main feature is Lake Banyoles (Girona, Spain). Chromatium, Lamprocystis and Chlorobium are the major phototrophic sulfur bacteria in Lake Ciso. Blooms of a photosynthetic cryptomonad (up to 5 X 10(5) ind ml-1) were found at the metalimnion. The community of ciliates could be divided in three groups: aerobic, cosmopolitan, genera such as Stentor and Vorticella, in the epilimnion; a large population (up to 10(4) ind ml-1) of Coleps, adapted to low concentrations of both oxygen and sulfide, together with a few individuals of the equally sulfide-tolerant genus Paramecium, in the metalimnion, and anaerobic, true sulfide-loving genera such as Plagiopyla and Metopus, in the hypolimnion, where sulfide concentration was between 0.6 and 1.2 mM. PMID- 3089343 TI - On plastid symbiosis in Tontonia appendiculariformis (Ciliophora, Oligotrichina). AB - Many hundreds of isolated plastids, in a good state of preservation in their living host, the planktonic ciliate Tontonia appendiculariformis (Oligotrichina), have been studied by electron microscopy. These distinctive plastids, located at the periphery of the host's body, which do not belong to complete symbiotic algae, are described in detail. All are bounded by three membranes. Although degenerating plastids were observed none were ever seen in division. Their possible origin, the significance of the three plastid membranes, and the degree of symbiosis established are discussed. From their organization, these plastids may have originated from several species of chromophyte algae, such as dinophyceae, Prymnesiophyceae, and Bacillariophyceae or Chrysophyceae. Because of their absence of division and of their possible degeneration, they are probably not integrated genetically. However, they appear to survive for some time and to remain functional. There is evidence that the outermost third plastid membrane arises from the host ciliate. Finally, hypotheses are proposed to explain the incorporation of the plastids into the ciliate, and their possible role in building cortical polysaccharide plates. PMID- 3089344 TI - [Ir-gene control of rat T-lymphocyte proliferation in response to Ig allotype]. AB - Antigen-induced T-cell proliferation in vitro was adapted to the estimation of antiallotypic response to Igk-Ib immunoglobulin k chain allotype of MSU/b and Fisher rats in WAG, August and FI (WAG X August) rats. August and FI rat T lymphocytes responded to Igk-Ib alloantigen with stimulation indexes (SI) 3.8-5.0 (high responders), while WAG rat T lymphocytes showed practically no response (SI 0.9-1.8--low responders). These results correlate well with our previous findings of Ir-gene-controlled antiallotypic in vitro reactions in these rat strains. Effective antigen presentation to FI anti-Igk-Ib T cells was observed only using Igk-Ib-pulsed antigen-presenting cells (APC) of August responders, but not of WAG non-responders. FI T cells responded well to PPD-pulsed APC of both rat strains. The data confirm Ir-Igk-Ib-gene control and, therefore, MHC-restriction of antiallotypic response in inbred rats. PMID- 3089345 TI - [The lack of generalized immunosuppression in C57BL/6 mice during progressive growth of syngenic T lymphoma EL-4 and Lewis lung carcinoma 3LL]. AB - The immune competence of C57Bl/6 mice implanted with EL-4 lymphoma of Lewis Lung carcinoma 3LL was investigated during 3 weeks after implantation. Splenic lymphocyte responses to mitogens (Con A, PHA, LPS, PWM) cytotoxic T lymphocytes (CTL) and interleukin-2 (IL-2) production were assessed. A dramatic reduction in mitogenic responses to Con A and PHA was observed during tumour progression. LPS and PWM responses were less depressed. Con A-induced IL-2 production correlated with Con A and PHA responses. Allospecific CTL response to mastocytoma P 815 was not decreased in syngeneic tumour-bearing mice. PMID- 3089346 TI - [Mechanism of the antidepressive and learning-stimulating effects of thyroliberin and its analogs]. AB - To define the role of different fragments of TRF molecule in its neurotropic activity a number of newly synthesized dipeptides of pyroglutamic acid with beta alanine residue, GABA or GABA ester have been studied. The compounds were compared with TRF in their ability to influence spontaneous or amphetamine stimulated locomotor activity in mice and to affect the elaboration of passive avoidance reflex in rats. Unlike TRF, the pyroglutamate dipeptides studied were shown to exhibit no activity in amphetamine potentiation test, thus providing additional evidence of the importance ofthe "histidylproline" fragment in TRF antidepressant effect. On the other hand, the above pyroglutamate derivatives caused a pronounced improvement in the learning abilities of under-trained rats. These dipeptides were shown to be more active in this test than TRF. This suggests the important role of pyroglutamyl moiety in the stimulation of the learning processes. PMID- 3089347 TI - [Mutagenic and antimutagenic properties of bemitil]. AB - Complex research of the genetic activity of a new 2-mercaptobenzimidazole derivative bemythyl has shown that the drug failed to induce recessive, age related lethal mutations in drosophila, dominant lethal mutations in germ mammalian cells and chromosomal damage in murine bone marrow cells and human peripheral blood cell cultures. The experiments on mice have demonstrated that therapeutic bemythyl doses caused a two-fold decrease in the level of aberrant cells induced by alkylating agents--fotrin and fopurin. PMID- 3089348 TI - The structure of the T cell antigen receptor genes in normal and malignant T cells. AB - In this review the genomic structure and the RNA transcripts of the alpha and beta chain of the T cell antigen receptor have been discussed. Studies of the structure of TcR beta in hematologic malignancies have revealed rearrangement in almost all of the T cell malignancies and a small proportion of non-T cell malignancies. In addition, clonal involvement of T cells in diseases such as Hodgkin's disease, angioimmunoblastic lymphadenopathy, and chronic T cell lymphocytosis have been observed. The study of the structure of the TcR beta gene is thus a useful tool for identifying clonal expansions of cells and in conjunction with studies of the immunoglobulin gene structure, and cell surface markers a useful tool for identifying cell lineage. At the present time the evaluation of the structure of the alpha chain genes has not been as fruitful. However, chromosome translocations involving the TcR alpha chain genes have been recognized and, in one case, this rearrangement has been in association with a known oncogene. With the isolation of more probes to the alpha chain region it should be possible to test its utility in identifying clonal populations and cell lineage. The recent isolation of the gamma gene of the T cell will also permit such studies. Preliminary results of studies carried out with a probe to the gamma chain gene of the T cell have paralleled results obtained with the TcR beta probe (unpublished observation). PMID- 3089349 TI - The structure of the T cell gamma chain gene in lymphoproliferative disorders and lymphoma cell lines. AB - During the development of B and T cells, a number of genes undergo rearrangement. In this paper we have studied the structure of the T cell gamma-chain gene in primary lymphomas and cell lines derived from patients with lymphoma. Samples derived from patients with angioimmunoblastic lymphadenopathy (AIL), Lennert's lymphoma, and Hodgkin's disease were also examined. TcR gamma was rearranged in all T cell lymphomas and in some B cell lymphomas and B cell lymphoma cell lines. Rearrangement of the gamma-chain gene was also found in AIL, Lennert's lymphoma, and four of eight cases of Hodgkin's disease. These studies indicate that rearrangement of TcR gamma is a useful clonal marker but does not aid in the identification of cell lineage. PMID- 3089350 TI - Experimental permeability edemas. PMID- 3089352 TI - The utility of a single-point dosing protocol for predicting steady-state lithium levels. AB - Two methods for predicting steady-state serum lithium level were compared prospectively in in-patients suffering from affective disorder. A single-point prospective administration model that required a single 24-hour serum lithium level, following a test dose produced statistically similar predictions of the observed steady-state lithium levels as did a model that required 12- and 36-hour levels. However, the latter two-point method produced significantly more accurate predictions from clinical interpretation. Although the two-point approach is preferable, the single-point method is clinically acceptable if its limitations of accuracy are taken into consideration. PMID- 3089351 TI - Endothelium-dependent inhibition of platelet aggregation. AB - In cascade perfusion and superfusion experiments on rabbit tissues, when acetylcholine (ACh) was introduced into the circuit so as to perfuse the aorta under perfusion with noradrenaline (NA), the effluent relaxed the transverse aortic strip which had been denuded of endothelium. The effluent from the perfused aorta which was capable of relaxing the transverse aortic strip also significantly inhibited platelet aggregation induced by arachidonic acid (AA) in a volume-related manner. The inhibitory activity was decreased by the prolongation of transit time before addition of the effluent to platelet-rich plasma. Neither the inhibition of AA-induced aggregation nor the relaxation of the transverse strip by the effluent could be observed after the removal of endothelium from the aorta, or after pretreatment of aorta with mepacrine or nordihydroguaiaretic acid (NDGA). The AA-induced platelet aggregation was unaffected by pretreatment of platelets with mepacrine or NDGA at the concentration tested. Pretreatment of aorta with indomethacin failed to modify the relaxation of the transverse strip induced by the effluent. These results strongly suggest that endothelium-derived vascular relaxant factor (EDRF) possesses inhibitory activity on AA-induced aggregation in addition to its vasodilator activity. PMID- 3089353 TI - Nephrotic syndrome after oral gold. PMID- 3089354 TI - Chemical treatment of stones in the biliary tree. PMID- 3089355 TI - Clinical and immunological results of segmental splenectomy in schistosomiasis. AB - We evaluated segmental splenectomy in 51 patients who required splenectomy to relieve the symptoms of schistosomal splenomegaly, and compared their course with that of 44 patients who underwent total splenectomy in an unrandomized study. We describe a minor modification of our initial technique. Patients having segmental splenectomy had a similar postoperative course to those having total splenectomy. Conversion of a segmental to a total splenectomy was required in two cases due to technical faults. No regrowth of the spleen has occurred in up to 4 years of observation. We noted an increased percentage of T lymphocytes with an increased ratio of T helper to T suppressor cells in patients having segmental splenectomy. Our cumulative experience supports adoption and wider evaluation of segmental splenectomy in schistosomiasis. PMID- 3089356 TI - Functional duodenal obstruction caused by radiotherapy after nephrectomy. PMID- 3089357 TI - Halothane and the liver: the problem revisited and made obsolete. PMID- 3089358 TI - Obese deceivers? PMID- 3089359 TI - Psoriasis. PMID- 3089360 TI - Salt and the glycaemic response. AB - The possibility that salt increases plasma glucose and insulin responses to starchy foods was investigated. Six healthy adults took four morning test meals randomly: 50 g carbohydrate as cooked lentils or white bread, with or without 4.25 g of added salt (an amount within the range of salt found in a meal). When salt was added to the lentils the incremental area under the three hour plasma glucose curve was significantly greater than that for lentils alone (43.2 mmol.min/l v 11.1 mmol.min/l (778 mg.min/100 ml v 200 mg.min/100 ml]. When salt was added to bread the peak glucose concentration was significantly higher than that for unsalted bread (6.96 mmol/l v 6.35 mmol/l (125 mg/100 ml v 114 mg/100 ml], and this was followed by relative hypoglycaemia. Plasma insulin concentrations at 45 minutes were higher after a meal of salted lentils and salted bread than after the unsalted foods (p less than 0.05). The high insulin concentration after salted bread was sustained for one hour after the meal, thus the mean area under the three hour curve was 39% greater than that for unsalted bread (p less than 0.05). Salt may increase the postprandial plasma glucose and insulin responses to lentils and bread by accelerating the digestion of starch by stimulating amylase activity or accelerating small intestinal absorption of the liberated glucose, or both. The findings of this preliminary study, if confirmed by others, would support the recommendation that diabetics, as well as the general population, should reduce their intake of salt. PMID- 3089361 TI - Assessment of oral candidiasis in patients with respiratory disease and efficacy of a new nystatin formulation. AB - Fifty consecutive patients with respiratory diseases who developed oropharyngeal candidiasis were assessed clinically and microbiologically before and after seven days' treatment with nystatin suspension or pastilles (a new formulation). In 45 patients in whom microbiology yielded positive results there was frequent associated use of oral corticosteroids, antibiotics, sedatives, and inhaled corticosteroid, while in a few patients atropine analogues may have predisposed to infection. Dentures were worn by 32 of the infected patients. Concomitant treatment of dentures in chronically infected patients appeared to improve the therapeutic response. Pastilles and suspension were equally efficacious both clinically and microbiologically. The potential for enhanced drug delivery to the oropharynx suggests that nystatin pastilles may be useful in patients in whom poor compliance seems likely. PMID- 3089362 TI - Clinical versus laboratory detection of alcohol abuse: the alcohol clinical index. AB - To determine reliable indicators of alcohol abuse a comprehensive set of clinical and laboratory information was acquired from three groups of subjects with a wide range of drinking histories: 131 outpatients with alcohol problems, 131 social drinkers, and 52 patients from family practice. Findings from clinical examination provided greater diagnostic accuracy than laboratory tests for detecting alcohol abuse. Logistic regression analysis produced an overall accuracy of 85-91% for clinical signs, 84-88% for items from the medical history, and 71-83% for laboratory tests in differentiating the three groups. Further analyses showed 17 clinical signs and 13 medical history items that formed a highly diagnostic instrument (alcohol clinical index) that could be used in clinical practice. A probability of alcohol abuse exceeding 0.90 was found if four or more clinical signs or four or more medical history items from the index were present. Despite recent emphasis on the laboratory diagnosis of alcohol abuse simple clinical measures seem to provide better diagnostic accuracy. PMID- 3089364 TI - Causalgia as a complication of meningococcal meningitis. PMID- 3089363 TI - Does super efficient starch absorption promote diverticular disease? AB - The amount of starch escaping absorption in the small intestine was measured in eight patients with symptomatic diverticular disease and eight controls. Unabsorbed starch was calculated from breath hydrogen measurements after a potato meal compared with the hydrogen response to lactulose. The proportion of unabsorbed starch was low in all the patients (mean 3.3%) and was only about a quarter of that in the controls (12.4%; p less than 0.01). These findings confirm that unabsorbed starch provides an important quantity of carbohydrate reaching the colon and suggest that super efficient starch absorption, by reducing this provision, may promote the development of diverticular disease. PMID- 3089365 TI - Clinical and financial implications of a district scheme to provide plastic insulin syringes to diabetics. PMID- 3089366 TI - A new resuscitation apparatus providing 70% oxygen. PMID- 3089367 TI - Papillitis and hepatitis B. PMID- 3089368 TI - Psychiatric morbidity in a general practice in an Indian city. AB - Psychiatric morbidity in an Indian general practice was studied using the 12 item version of the General Health Questionnaire to screen 882 patients who represented 9000 consecutive adult patients attending the practice. The questionnaire was valid with a cutting score of 1/2 when compared with section 1 of the standardised Indian Psychiatric Survey Schedule. The probable prevalence of psychiatric morbidity was 35.9%. The general practitioner identified only about 25% of patients. Five of the 12 questions on the General Health Questionnaire had a higher discriminatory capacity, and the performance of the patients on these five questions was valid when compared to section 1 of the Indian Psychiatric Survey Schedule. PMID- 3089369 TI - Prenatal screening for congenital heart disease. AB - Routine ultrasound examination of the fetus is already established in most obstetric units in Britain. A simple method was devised to evaluate one section of the fetal heart systematically. Examination of this section, the four chamber view, may readily be incorporated into routine obstetric screening. Severe cardiac abnormalities detectable in this view occur in two per 1000 pregnancies. For six years the department of paediatric cardiology at Guy's Hospital, London, served as a referral centre for fetal echocardiography. As teaching became more widespread an increasing proportion of cases of cardiac anomaly were referred because the obstetrician suspected abnormality on examination of the four chamber view. Currently 80% of detected abnormalities are referred for this reason. Further extension and organisation of teaching might result in most severe cardiac malformations being detected in early prenatal life. PMID- 3089370 TI - Nursing dependency in registered nursing homes and long term care geriatric wards in Edinburgh. AB - There has been growing interest and public investment in registered nursing homes, apparently based on the assumption that these homes are the private equivalent of hospital long term care. We have tested this hypothesis in a survey comparing 400 patients in 18 registered nursing homes with 217 patients in 11 geriatric long term care wards in Edinburgh. The nursing home patients formed a distinct and separate group: 362 (92%) were women, 392 (98%) were single or widowed, and 358 (90%) were self financing, whereas in the geriatric long term care group 148 (68%) were women and 35 (16%) were still married. Patients in nursing homes were also far less dependent than those in geriatric long term care wards (p less than 0.005). This study suggests that there may be large differences between the patients in these two types of institution, particularly with regard to nursing dependency. This finding has important implications in the future planning of long term places for the dependent elderly. PMID- 3089371 TI - ABC of resuscitation. The airway at risk. PMID- 3089372 TI - An outbreak of gastrointestinal illness associated with consumption of raw depurated oysters. PMID- 3089373 TI - Length of survival of patients with acquired immune deficiency syndrome in the United Kingdom. AB - An analysis of the lengths of survival of patients with the acquired immune deficiency syndrome presenting with different opportunistic diseases was performed using epidemiological data routinely collected at the PHLS Communicable Disease Surveillance Centre. The overall crude case fatality rate was 55.4% (93/168). The median survival times were: 21.2 months for Kaposi's sarcoma, 12.5 months for Pneumocystis carinii pneumonia, and 13.3 months for other opportunistic infections. The shortest median survival time (6.6 months) was found for those with both Kaposi's sarcoma and P carinii pneumonia. There were significant differences between durations of survival of patients with Kaposi's sarcoma and those with all other diseases, which indicated impaired cellular immunity apart from opportunistic infections. This analysis shows that those with Kaposi's sarcoma alone have the most favourable prognosis. PMID- 3089374 TI - Successful rehabilitation in conversion paralysis. AB - A rehabilitation programme for patients with conversion paralysis has been introduced in which they are offered physical rehabilitation. During an eight month period between October 1984 and May 1985 six patients who had been diagnosed as dependent on wheelchairs owing to conversion paralysis for a mean of 3 years (range 1-6 years) were entered into the inpatient neurorehabilitation programme. All six patients were able to walk within a mean of 41 days (range 10 70 days), and then relinquished a variety of aids and allowances as a result of their regained mobility. They continued to be independent at outpatient review for a mean of 10 months (range 8-15 months). Successful rehabilitation from wheelchair dependency can be achieved by a cost effective, prolonged, inpatient neurorehabilitation programme. PMID- 3089375 TI - Chickenpox isolation: is it worth the trouble? PMID- 3089376 TI - Steroids, the eye and general practitioners. PMID- 3089378 TI - Pseudo-obstruction. PMID- 3089377 TI - Gastrointestinal investigation of iron deficiency anemia. PMID- 3089379 TI - Mouth to mask respiration. PMID- 3089380 TI - Resuscitation in the accident and emergency department. PMID- 3089381 TI - Resuscitation by ambulance crews. PMID- 3089382 TI - Dangers of lumbar puncture. PMID- 3089383 TI - IVF update. PMID- 3089385 TI - Ultrasound diagnosis of bile duct calculi. PMID- 3089384 TI - Aspirin for unstable angina? PMID- 3089386 TI - Accuracy of home blood glucose monitoring by children. PMID- 3089387 TI - Investigation of cholinesterase in amniotic fluid. PMID- 3089388 TI - Are solar keratoses more common on the driver's side? PMID- 3089389 TI - The practice nurse: is history repeating itself? PMID- 3089390 TI - Use of molar units for drugs and toxins? PMID- 3089391 TI - Timer: a new objective measure of consultation content and its application to computer assisted consultations. AB - As part of the research into the effect in the consultation of the use of a computer to prompt opportunistic preventive care a valid, objective, and practical measure of the consultation process was required. After a review of the alternative methods the Time Interval Medical Event Recorder (Timer) was developed, its reliability tested, and applied to 93 control consultations and 49 computer assisted consultations. Timer records, every five seconds, four consultation events: the problems being dealt with, the physical activity, the verbal activity, and the secondary tasks being attempted. Timer showed that control consultations lasted an average of 6 minutes 58 seconds. The doctors spent 35% of their time on administration, and patients and doctors were both conversational for just 33% of the consultation. Giving information was the most common verbal activity (48% of the duration of the consultation) with silence accounting for 21% of the time. When the computer was used the average consultation was longer, at 7 minutes and 46 seconds. The doctor's contribution to the consultation appeared to have increased. Patient centred speech fell from 36% in controls to 28% of the duration of the consultation when the computer was used, while doctor centred speech rose from 30% to 34.5%. Secondary tasks (exploring patient concepts, education, management sharing, and prevention) were attempted during 28% of the control consultations and 40% of the computer consultations. This was accounted for by the increase in prevention (p less than 0.001). Timer is a reliable and practical tool for researching the consultation, and though it has shown validity in detecting differences between consultations that use a computer and those that do not, further applications are required to establish its full value. PMID- 3089392 TI - Better a commitment to health and research than to missiles. PMID- 3089393 TI - Does sodium restriction lower blood pressure? AB - Data from 13 randomised trials on the effect of sodium restriction on blood pressure were analysed. The hypotensive effect of sodium restriction was found to be small and restricted largely to systolic blood pressure, which fell by an average of 3.6 mm Hg (range 0.5-10.0 mm Hg). The reduction increased with age and in those with higher blood pressure. Sodium restriction therefore seems to be of limited use in those who are most eligible for non-pharmacological treatment of high blood pressure--namely, young patients with mild hypertension. PMID- 3089394 TI - ABC of resuscitation. Training and retention of skills. PMID- 3089395 TI - Acute hepatitis B in patients in Britain related to previous operations and dental treatment. AB - The frequency of transmission of hepatitis B virus infection from health service staff to patients was assessed from reports of confirmed cases of acute clinical hepatitis in 1980-3. During the four years 4505 reports (91% of the total) included replies to a question about recent operations; 153 patients (3.4%) had this history. Transfused blood or blood products were considered the source for 27 cases (0.06%). Eleven patients (0.02%) were infected in two clusters, both in cardiac surgery units; six were caused by a perfusion technician, who was a symptomless carrier, and five by a surgical registrar during the incubation period of an acute hepatitis B infection. The estimated average annual risk of a patient developing acute hepatitis B as part of a cluster caused by staff during surgical procedures was one in a million operations. For another 11 patients blood transfusion could not be excluded as a source. Where no association between surgery and hepatitis was found the incidence of a history, lay between 2.3 and 2.6%. The Hospital In-Patient Enquiry data showed that about 2.4% of the population had had operations in a six month period. These findings suggest that transmission of hepatitis B infection from staff to patients is rare in Britain and that the small risk could be eliminated by attention to measures to preserve asepsis and by immunising staff at risk. PMID- 3089396 TI - Acute viral hepatitis B: laboratory reports 1980-4. PMID- 3089397 TI - Resolution of dyskinesia and the "on-off" phenomenon in thyrotoxic patients with Parkinson's disease after antithyroid treatment. PMID- 3089399 TI - Why are patients with acute stroke admitted to hospital? PMID- 3089398 TI - Differential diagnosis of dementia. PMID- 3089400 TI - Diffuse peritonitis and chronic ascites due to infection with Chlamydia trachomatis in patients without liver disease: new presentation of the Fitz-Hugh Curtis syndrome. AB - Two women were admitted for increasing abdominal pain, vaginal discharge, and severe or moderate chronic ascites. Diffuse peritonitis without evidence of liver disease was found in both cases, and in one the ascites and vaginal discharge contained Chlamydia trachomatis. Both patients responded to doxycycline, and this and the laboratory findings pointed strongly to C trachomatis as the aetiological agent. C trachomatis may cause severe peritoneal infections with chronic ascites formation in the absence of liver disease in women with the Fitz-Hugh-Curtis syndrome. Prompt diagnosis and antibiotics lead to rapid cure. PMID- 3089401 TI - Motor neurone disease presenting as respiratory failure. PMID- 3089402 TI - Non-steroidal anti-inflammatory drugs and serious gastrointestinal adverse reactions. PMID- 3089403 TI - Irreversible pulmonary hypertension after treatment with fenfluramine. PMID- 3089404 TI - Cigarette smoking and risk of premature stroke in men and women. AB - A case-control study was carried out of the relation between cigarette smoking and hypertension and stroke. A total of 132 cases of stroke (79 in men, 53 in women) identified as a part of a population based register were compared with 1586 controls (1017 men, 569 women) from a survey of cardiovascular risk factors conducted in the same population. Cigarette smokers had a threefold increase in the risk of stroke compared with current non-smokers. This association remained significant after adjusting for hypertension. Those who both smoked and had hypertension had an increased risk of stroke of almost 20-fold compared with those who neither smoked nor had hypertension. Overall, in this population roughly 37% of stroke events may be attributed to cigarette smoking and 36% to hypertension. PMID- 3089405 TI - Serial visual evoked potential recordings in Alzheimer's disease. AB - Primary presenile dementia slows the major positive component of the visual evoked potential to flash stimulation but does not affect the visual evoked potential to patterned stimulation. The progressive effect of Alzheimer's disease was followed in a 58 year old woman over three and a half years from the development of the earliest symptoms to complete mental incapacity. The pattern reversal visual evoked potential remained normal, but the flash visual evoked potential gradually slowed from 129 ms in 1981 to 153 ms in 1984. The severity of the abnormality of the flash visual evoked potential thus reflected the severity of the dementia. Electroencephalography, computed tomography, and psychometric tests indicated generalised cortical disease, but the results were not specific to dementia. The combination of a slowed flash and normal pattern visual evoked potential seems to be specific to Alzheimer's disease and supports the use of flash and pattern visual evoked potentials in routine diagnostic testing for this condition. PMID- 3089406 TI - Patterns of fractures in accidental and non-accidental injury in children: a comparative study. AB - The incidence and pattern of fractures in children who had been abused were compared with those of fractures sustained by children of similar ages in whom abuse had been excluded. From 1976 to 1982 there were 35 children with fractures resulting from child abuse, and all were aged under 5. Of the 826 children in the control group, seen from January to June 1981, 85% were aged over 5. Abused children were much more likely to have multiple fractures (p less than 0.001) and bruising of the head and neck (p less than 0.001). Fractures of the ribs were common in children who had been abused, and their presence, in the absence of major chest trauma, strongly suggested that abuse was occurring. Injuries to the long bones were invariably spiral or oblique fractures or subperiosteal new bone formation--both "gripping or twisting" injuries. Spiral fracture of the humeral shaft was significantly more common (p less than 0.001) in the group of abused children. Classic metaphyseal chip fractures were uncommon. One child in eight aged under 18 months who sustains a fracture may be a victim of child abuse. PMID- 3089407 TI - Opiate withdrawal: inpatient versus outpatient programmes and preferred versus random assignment to treatment. AB - The relative effectiveness of an inpatient and an outpatient withdrawal programme for opiate addicts was studied. Forty five men and 15 women (mean age 26.13 (SD 5.12) years) took part in the study, all of whom were voluntary patients at the drug dependence clinic of the Maudsley Hospital in London between 1984 and 1985. Subjects were asked if they were prepared to accept either inpatient or outpatient withdrawal, and those who were willing to do so were assigned randomly to the randomised outpatient group or the randomised inpatient group. Those who expressed a strong preference were assigned, as appropriate, to the preferred outpatient group or the preferred inpatient group. Addicts in the inpatient group were more likely to achieve complete withdrawal (25 out of 31, 81%) than those in the outpatient group (five out of 29, 17%). This difference could not be attributed to pretreatment factors related to drugs or to social or psychological differences between the groups. These results have clinical and policy implications for the treatment of opiate addicts. PMID- 3089408 TI - Effect of dietary supplementation with fish oil on systolic blood pressure in mild essential hypertension. PMID- 3089409 TI - Are swelling and aching of the legs reduced by operation on varicose veins? PMID- 3089410 TI - Antithyroid action of carbocisteine. PMID- 3089411 TI - Randomised trial of compliance with screening for colorectal cancer. AB - A randomised trial of compliance with screening for colorectal cancer by means of the haemoccult test was conducted in Farnborough and Basingstoke districts. In each of the 14 participating practices (41 general practitioners) 25 852 men and women aged between 40 and 70 years were randomly allocated by household to one of six groups. The group determined the method of invitation to screening: a letter and the test were sent to the patient, or a letter with an appointment to attend the surgery was sent, or during a routine consultation the general practitioner invited patients to participate, and some patients received an educational booklet about bowel disorders and screening. Of the 17 824 people who were offered screening, 7545 (42%) complied. Compliance was significantly affected by the method of invitation, but not by whether an educational booklet was received, and was highest (57%) in the group that was offered the haemoccult test during a routine consultation (the "opportunistic" approach). In this group the compliance rate achieved by individual general practitioners ranged from 26% to 82%. Compliance was significantly higher in Farnborough, in the older (55-70) age group, in women, and in households in which two or more people were offered screening. The higher compliance in Farnborough may be explained by the higher proportion of older people and by the higher proportion of people living in households of two or more in the population that was offered screening. The fact that the screening programme in Farnborough was offered to the whole community and that the researcher may have acted as a facilitator were probably also important. One per cent of the patients screened had a positive test, and 24 (38%) of the 63 patients who were positive and were investigated in hospital had neoplastic disease. The yield was 1.2 cancers and 1.2 benign adenomas (1 cm or larger in size) per 1000 people screened. This low yield is likely to be a consequence of the relatively young age group screened. PMID- 3089412 TI - Long term transtracheal oxygen delivery through microcatheter in patients with hypoxaemia due to chronic obstructive airways disease. AB - Transtracheal administration of oxygen is a new technique for long term treatment. Twenty patients with hypoxaemia due to chronic obstructive airways disease were studied while receiving oxygen through a microcatheter inserted percutaneously into the trachea. By bypassing most of the dead space and avoiding oxygen wastage at the face this method of delivery reduced oxygen requirements by roughly half compared with delivery through nasal cannulas, thus reducing costs and facilitating portable treatment. Twelve of these patients continued to use the system for up to 13 months in preference to using nasal cannulas. Two important complications were a staphylococcal infection and a fractured catheter. Transtracheal oxygen reduced breathlessness and helped patients with routine daily activities. Transtracheal administration of oxygen is a practical method of treatment which may have an important role in rehabilitating patients with chronic lung disease. PMID- 3089413 TI - Discoveries on muscle: observation, theory, and experiment. PMID- 3089414 TI - ABC of resuscitation. Drowning and near drowning. PMID- 3089416 TI - A threat to psychiatric research? PMID- 3089415 TI - Prospective survey of performance of medical students during preclinical years. AB - The performance during the preclinical course of 517 students who had applied to this medical school for admission in 1981 and who had been accepted by the school or by another British medical school was analysed in relation to variables measured at the time of application to find factors that predicted success in the preclinical course, whether students chose to take an intercalated degree, and the class achieved in the intercalated degree. Thirty one of the 507 students who entered medical school withdrew from the course or failed their examinations; these students were particularly likely not to have an A level in a biological science. O level grades were of minimal predictive value for performance during the preclinical course. A level grades discriminated between successful and unsuccessful students but had too low a specificity or sensitivity to be of use in individual prediction. Mature entrants performed better overall than school leavers. Background variables accounted for only 14.2% of the variance in performance, implying that motivation and personality may be more important in determining performance. The 80 students who chose to take an intercalated degree were more likely to be men and not to be mature entrants; for a further 50 students intercalated degrees were obligatory. Performance in the intercalated degree related to performance during the preclinical course and to assessments made at the selection interview but not to achievement at O or A level. PMID- 3089417 TI - Lyme disease in a Hampshire child. PMID- 3089418 TI - Strokes among black people in Harare, Zimbabwe. PMID- 3089419 TI - Comprehensive bibliography database using a microcomputer. PMID- 3089420 TI - Serious adverse gastrointestinal reactions to non-steroidal anti-inflammatory drugs. PMID- 3089421 TI - Bone densitometry. PMID- 3089422 TI - Biological markers of alcohol intake among subjects injured in accidents. PMID- 3089424 TI - Standard of manuscripts submitted to medical journals. PMID- 3089423 TI - Randomised trials and informed consent in neonatal medicine. PMID- 3089425 TI - "Hospital medical staffing: achieving a balance". PMID- 3089426 TI - High quality at Scarborough Hospital. PMID- 3089427 TI - "Small is beautiful" in Whitby. PMID- 3089428 TI - A promising package on hospital staffing. PMID- 3089429 TI - Managing Raynaud's phenomenon. PMID- 3089430 TI - Advances in the treatment of facial deformity. PMID- 3089432 TI - Whatever happened to the Black report? PMID- 3089431 TI - Dilated cardiomyopathy, myocarditis, and the bioptome. PMID- 3089434 TI - The MRC and informed consent. PMID- 3089433 TI - Influence of intrinsic sympathomimetic activity on respiratory function during chronic beta blockade: comparison of propranolol and pindolol. AB - The long term effect of beta blockers and the influence of intrinsic sympathomimetic activity on respiratory function were assessed in patients with chronic stable angina pectoris randomised to receive treatment with propranolol (n = 21) or pindolol (n = 19) for one year. Forced expiratory volume in one second (FEV1) had fallen by a mean of 240 ml after one year (p less than 0.001) in those treated with propranolol compared with 120 ml in those treated with pindolol (p less than 0.05). The difference between the groups was significant (p less than 0.01). Vital capacity fell significantly only in those treated with propranolol (p less than 0.05 at one year). In those in whom the basal ratio of FEV1 to forced vital capacity was low (less than 70%) propranolol, but not pindolol, caused a significant (p less than 0.05) fall in FEV1 throughout treatment. Long term administration of pindolol has a less adverse effect on respiratory function than propranolol, which results in a progressive deterioration in respiratory function over one year. PMID- 3089435 TI - Penicillin: 1929-40. PMID- 3089436 TI - Coeliac axis compression syndrome. PMID- 3089437 TI - Paying for old age. PMID- 3089438 TI - Markers of HTLV-III in patients with end stage renal failure treated by haemodialysis. AB - Patients and members of staff from a haemodialysis unit were tested for markers of infection with human T cell lymphotropic virus type III (HTLV-III), the virus associated with the acquired immune deficiency syndrome (AIDS). An enzyme linked immunosorbent assay showed eight of 100 patients to have antibodies to HTLV-III. In five of these patients past or present infection with HTLV-III was confirmed by Western blot analysis or detection of HTLV-III antigens in lymphocyte cultures, or both. Investigation of other risk factors for AIDS showed that the putative source of HTLV-III was unrelated to dialysis in two patients whereas blood transfusion was the most likely cause of contamination in the others. No member of staff gave a positive result in the enzyme linked immunosorbent assay. Nosocomial transmission of HTLV-III seems unlikely if precautions similar to those recommended for the control of hepatitis B infection are applied. PMID- 3089439 TI - Short course of steroids in home treatment of children with acute asthma. AB - A double blind, randomised, placebo controlled study of the treatment of children with acute asthma at home showed that a three day course of prednisolone hastened improvement of both asthmatic symptoms and peak expiratory flow rates. Thus all asthmatic children who present with an acute attack should be considered for treatment with corticosteroids in addition to bronchodilators not only to prevent possible deterioration but also to speed recovery. PMID- 3089440 TI - Technetium-99m autologous phagocyte scanning: a new imaging technique for inflammatory bowel disease. AB - A method to determine the extent of active inflammatory bowel disease using selective labelling of autologous neutrophils and monocytes by phagocytosis of a technetium-99m (99mTc) stannous oxide colloid is described. Unlike leucocyte scanning techniques using Indium-III (IIIIn), the 99mTc colloid scan uses a cheap, readily available isotope, which specifically labels phagocytes. Scan results in 20 patients with inflammatory bowel disease were compared with barium examinations and colonoscopic appearances. There was close agreement in 15 of 20 patients as to the extent of mucosal disease. In four cases the scan showed more extensive disease than was suggested by barium examination. The scan showed terminal ileal Crohn's disease in three patients in whom the barium studies of the ileum had been reported as normal. In four patients with inactive disease and normal barium examinations no activity was seen on the scans. The 99mTc phagocyte scan is a sensitive, reliable means of determining the extent of active inflammatory bowel disease and can be used to quantify disease activity. PMID- 3089441 TI - Prevalence of antibody to HTLV-III in haemophiliacs in the United Kingdom. PMID- 3089442 TI - Prevention of cardiovascular disease in general practice: a proposed model. AB - A screening model based in general practice for the detection of subjects at risk of premature cardiovascular disease is described. Opportunistic screening is performed by a trained nurse who also gives initial advice on management. Immediate feedback to patients is possible since a rapid dry chemistry technique is used to measure blood cholesterol concentrations. The collation and analysis of data are achieved using a microcomputer. A central deidentified database is incorporated to allow epidemiological studies and intervention strategy evaluations to be made. Nineteen health centres have evaluated the model, and 40,000 subjects have been screened: 10% had diastolic blood pressures of over 95 mm Hg and 15% had a blood cholesterol concentration over 7 mmol/l (270 mg/100 ml) and 2% over 9 mmol/l (347 mg/100 ml). The initial data suggest that the model is acceptable to both health centre personnel and the general public and that the offer of screening is taken up by all elements of the target population. PMID- 3089443 TI - Cryotherapy for advanced carcinoma of the trachea and bronchi. AB - Cryotherapy was used to relieve symptoms in 75 patients suffering from advanced carcinoma of the trachea or bronchi. In all patients surgical resection, radiotherapy, or chemotherapy had been tried and been unsuccessful or had been thought to be unsuitable because of the patients' poor general condition. In cryotherapy the intraluminal tumour was frozen through a Stortz bronchoscope. Localised necrosis increased the patency of the lumen of the trachea or bronchi, resulting in relief of symptoms. Cryotherapy is effective and easily performed and causes the patient little discomfort. PMID- 3089444 TI - ABC of resuscitation. The ethics of resuscitation. PMID- 3089445 TI - Report from the PHLS Communicable Disease Surveillance Centre. PMID- 3089447 TI - Intercalated degrees. PMID- 3089446 TI - Topical minoxidil for common baldness. PMID- 3089448 TI - Non-steroidal anti-inflammatory drugs and the kidney. PMID- 3089449 TI - The law tries to decide whether whooping cough vaccine causes brain damage: Professor Gordon Stewart gives evidence. PMID- 3089450 TI - Bone mineral content in Polynesian and white New Zealand women. PMID- 3089451 TI - Impaired microvascular hyperaemic response to minor skin trauma in type I diabetes. PMID- 3089452 TI - Steroids, the eye, and general practitioners. PMID- 3089453 TI - Maternal mortality and the postpartum interval. PMID- 3089454 TI - Assessment of thyroid function: complications after treatment with fenoprofen. PMID- 3089455 TI - Spoiled soft contact lenses. PMID- 3089456 TI - Occupational asthma due to methylmethacrylate bone cement. PMID- 3089457 TI - Short term high doses of etidronate in Paget's disease. PMID- 3089458 TI - Transcutaneous oxygen tension during exercise in patients with claudication. PMID- 3089459 TI - Did the drug do it? PMID- 3089460 TI - The leaking labyrinth. PMID- 3089461 TI - Child health services in the community: making them work. PMID- 3089462 TI - Bladder dysfunction in progressive autonomic failure. PMID- 3089463 TI - Graduated elastic stockings. PMID- 3089464 TI - Mrs Short's recipe for better prison health. PMID- 3089465 TI - Angina pectoris-like pain provoked by intravenous adenosine in healthy volunteers. AB - In a study to characterise the chest pain induced by adenosine this agent was given as a bolus into a peripheral vein to six healthy volunteers (five men) aged 30-44. On the first day the maximum tolerable dose was determined in each case. On the second day three doses of adenosine (one third, two thirds, and the full maximum tolerable dose) and three doses of saline were given single blind in randomised order. Thereafter aminophylline 5 mg/kg was given and the procedure repeated in a different randomised order. On the third day between two thirds and the full maximum tolerable dose was given followed by 10 mg dipyridamole intravenously and a second injection of the same dose of adenosine. Heart rate and atrioventricular blocks were recorded by electrocardiography. One minute after each dose of adenosine the chest pain was scored. The maximum tolerable dose of adenosine ranged from 10.6 to 37.1 mg. All subjects experienced uneasy central chest pain provoking anxiety. The pain radiated to the shoulders, ulnar aspect of the arms, epigastric area, back, and into the throat. The pain began about 20 seconds after the injection and lasted 10-15 seconds. Increasing the dose of adenosine increased the intensity of the pain. Administration of aminophylline reduced the pain significantly. Second degree heart block was recorded in five of the six subjects during the time that the pain was experienced. After aminophylline no block was observed. Dipyridamole increased the intensity of pain. The duration of second degree heart block increased in four of the subjects, and in two of these third degree heart block occurred. These findings suggest that adenosine released from the myocardium during ischaemia induces angina pectoris by stimulating theophylline sensitive receptors. PMID- 3089466 TI - Effect of maternal dietary exclusion on breast fed infants with eczema: two controlled studies. AB - Thirty seven breast fed infants with eczema were studied to see whether changes in their mothers' diets affected their skin condition. Nineteen mothers and babies took part in a double blind crossover trial of exclusion of egg and cows' milk, and 18 took part in open exclusion of 11 foods followed by double blind challenge to those mothers whose infants seemed to respond. Babies were examined at the beginning and end of each dietary period, and the extent and severity of the rash were given a numerical score. The eczema improved in six infants when their mothers avoided egg and cows' milk and worsened again when these were reintroduced. Two infants suffered gastrointestinal reactions after maternal ingestion of egg and cows' milk, one developing colitis. Maternal dietary exclusion seems to benefit some breast fed babies with eczema. PMID- 3089467 TI - Accuracy and reproducibility of a new contrast clearance method for the determination of glomerular filtration rate. AB - A new method for determining the glomerular filtration rate was analysed prospectively. The method uses an x ray fluorescence technique to measure disappearance from the plasma of injected non-ionic iodinated contrast media. Eighty seven patients were studied. Fifty four had an intravenous dose of 100 ml iohexol (Omnipaque) and 33 had 50 ml iohexol. Clearances of chromium-51 labelled edetic acid (51Cr-EDTA) were measured simultaneously. In the patients given 100 ml iohexol there was excellent correlation with 51Cr-EDTA clearance (r = 0.90). The correlation using 50 ml iohexol was also good (r = 0.85). Correlation between creatinine clearance and clearance of 51Cr-EDTA in 33 patients was less satisfactory (r = 0.69). There were no adverse reactions to the contrast media. The equipment used for measuring contrast clearance was robust and simple to operate. Freezing plasma samples in 10 studies and re-examining them weekly for six weeks showed no significant variation in results; hence reproducibility was good. This new and accurate method for determining the glomerular filtration rate merits further study and might find a useful place in routine clinical practice. PMID- 3089469 TI - Captopril in elderly patients with heart failure. PMID- 3089468 TI - Prevalence of multiple sclerosis in a south London borough. AB - A survey of multiple sclerosis in the London Borough of Sutton, population 169,600, yielded 195 cases, giving an overall prevalence of 115/100,000. This is the third highest prevalence for a first survey of a geographical area in the United Kingdom, exceeded only by 127/100,000 in north east Scotland and 134/100,000 in Shetland. On the classification system of Allison and Millar, three quarters of the cases were classified as probable multiple sclerosis, 15% as early probable and latent multiple sclerosis, and 10% as possible multiple sclerosis. The mean age was 49 years, the mean age at onset was 34 years, and the mean duration of the disease was 15.4 years. The age standardised female to male ratio was 2:1. The prevalence found in this survey does not differ significantly from that recorded in the first north east Scotland survey. This study suggests that, firstly, the prevalence of multiple sclerosis in south east England is probably about 100/100,000 and, secondly, the latitudinal effect on the prevalence of multiple sclerosis in the United Kingdom is less appreciable than previously believed. PMID- 3089470 TI - Cannulation of difficult oesophageal strictures with angiographic catheters. PMID- 3089471 TI - Primary biliary cirrhosis after benoxaprofen. PMID- 3089472 TI - Predicting risk of diabetic ketoacidosis in patients using continuous subcutaneous insulin infusion. PMID- 3089473 TI - Spontaneous pneumomediastinum in two stowaways. PMID- 3089474 TI - Life threatening reaction to tuberculin testing. PMID- 3089475 TI - Natural killer cells in insulin dependent diabetes mellitus. PMID- 3089476 TI - Diagnosing cancer in general practice: when is cancer suspected? AB - Of 10,278 encounters with patients recorded by 33 general practitioners in a defined Norwegian population during a two month period, 429 (4.2%) were classified as resulting in a follow up for suspected cancer. The patient's fear of cancer was the most important indicator of suspicion of cancer among the doctors. Patients who consulted for digestive and gynaecological problems were most frequently suspected of having cancer. Comparing the pattern of suspicion of cancer with the incidence of cancer in the area showed a relative oversuspicion in young patients and women. PMID- 3089477 TI - Slipped capital femoral epiphysis: continuing problem of late diagnosis. PMID- 3089478 TI - Recommendations on the use of living kidney donors in the United Kingdom. British Transplantation Society. PMID- 3089479 TI - The central dilemma: destroy or develop. PMID- 3089480 TI - Psoriasis. PMID- 3089481 TI - Does sodium restriction lower blood pressure? PMID- 3089482 TI - Sodium excretion in young children. PMID- 3089483 TI - Treatment of the premenstrual syndrome by subcutaneous oestradiol implants and cyclical oral norethisterone. PMID- 3089484 TI - Gastrointestinal investigation of iron deficiency. PMID- 3089485 TI - Severity scoring in intensive care. PMID- 3089486 TI - Hazards of bronchoscopy. PMID- 3089487 TI - Cryptosporidium and diarrhoea. PMID- 3089488 TI - More action for community nurses. PMID- 3089489 TI - A rise is a rise is a rise. PMID- 3089490 TI - Hypersensitivity of lung vessels to catecholamines in systemic hypertension. AB - Among patients with primary systemic hypertension pressure and arteriolar resistance in the pulmonary circulation exceed normal values and are hyper reactive to sympathetic stimulation. A study was therefore carried out in 16 patients with uncomplicated essential hypertension and nine healthy subjects to compare the pulmonary vascular reactivity to exogenous catecholamines. In the normotensive group the dose response relation to adrenaline (microgram: dyn) was 1 = -4, 2 = -9, 3 = -9, and 4 = -10 and to noradrenaline 2 = +3, 4 = /8, 6 = +4, and 8 = +3. The relations in the hypertensive subjects were 1 = +18, 2 = +42, 3 = +59, and 4 = +77 and 2 = +39, 4 = +54, 6 = +76, and 8 = +100, respectively. Group differences were highly significant. Cardiac output (blood flow through the lungs) was raised by adrenaline and reduced by noradrenaline. In either case the driving pressure across the lungs was significantly augmented in the hypertensive patients but not in the normotensive group. Both catecholamines had a vasoconstrictor effect on the pulmonary circulation as a result of vascular over reactivity. The opposite changes in resistance between normal and hypertensive subjects produced by adrenaline suggest that a constrictor vascular hypersensitivity occurs in the pulmonary circulation with the development of systemic high blood pressure. PMID- 3089491 TI - Influence of dietary linoleic acid on leucocyte sodium transport and blood pressure. AB - In a randomised double blind study to determine whether an increase in the polyunsaturated fat linoleic acid might influence leucocyte membrane sodium transport 22 normotensive volunteers received an oral supplement of linoleic acid or placebo daily for four weeks. Mean total sodium efflux rose significantly during supplementation with linoleic acid compared with placebo. In addition, all components of lying and standing blood pressure fell, though only the fall in supine systolic pressure was significant. Dietary supplementation with linoleic acid may alter ion fluxes across the cell membrane, presumably through changes in its physicochemical structure. In addition, the change in fat intake may lower blood pressure, though to only a very modest extent. PMID- 3089492 TI - Increased incidence of menstrual abnormalities and hysterectomy preceding primary biliary cirrhosis. AB - A study was performed to assess the incidence of previous hysterectomy and dilatation and curettage among women with primary biliary cirrhosis. In 87 patients with primary biliary cirrhosis hysterectomy or dilatation and curettage had been performed significantly more often than among 100 age matched normal controls and 80 age matched patients with chronic active hepatitis or alcoholic liver disease. Among the 47 patients with primary biliary cirrhosis who had undergone hysterectomy or dilatation and curettage operations had been performed at a mean of 10.7 years and 13.2 years, respectively, before the onset of disease. The main indication for hysterectomy among patients with primary biliary cirrhosis and controls was menorrhagia. These menstrual disorders may be a consequence of high concentrations of oestrogens in patients with primary biliary cirrhosis. PMID- 3089493 TI - Onset of obesity in a 36 year birth cohort study. AB - A large national cohort of children studied from birth to 36 years was used to test the predictive value of childhood obesity for obesity in adult life. Only 21% (39) of obese 36 year olds had been obese at age 11 years, and even when associated social factors were taken into account the correctly predicted percentage was much lower than the prediction rate achieved using body mass data from age 26 years. The comparatively poor predictive value of childhood obesity and the association of adult obesity with educational achievements and socioeconomic circumstances of family of origin emphasise the need for encouraging good nutritional and exercise habits rather than placing undue emphasis on the control of childhood obesity. PMID- 3089495 TI - Plasma cholesterol concentration and death from coronary heart disease: 10 year results of the Whitehall study. AB - Ten year mortality from coronary heart disease in 17,718 middle aged men was related to their initial plasma cholesterol concentrations. The relative risk of death from coronary heart disease declined with age, but the absolute excess risk did not. The risk gradient was continuous over the whole range of cholesterol concentrations, the lowest mortality being among men with concentrations below the lowest decile. It seems that, as with blood pressure, the average cholesterol concentration in the blood pressure, the average cholesterol concentration in the population is too high: lowest concentrations are prognostically the best. A quarter of all deaths from coronary heart disease related to cholesterol occurred among men with concentrations above the top decile, but 55% occurred among men with concentrations in the middle three fifths of the distribution; this figure of 55% could be reduced only by a policy aimed at lowering concentrations in the whole population. PMID- 3089494 TI - Influence of passive smoking on admissions for respiratory illness in early childhood. AB - An association was sought between passive smoking and inpatient admissions for respiratory illness in 1058 children born between 1 June and 31 December 1981 and living in the neighborhoods of Nan-Jing Western Road and Yan-An Western Road in Jing-An District, Shanghai. The admission rate for first episodes of respiratory illness was positively correlated with the total daily cigarette consumption of family members during the children's first 18 months of life. The relative risk of developing a first episode of respiratory illness was 1.80 for children living in families including people who smoked 10 or more cigarettes a day compared with those living in non-smoking families. Multiple logistic regression analysis showed that the effect of passive smoking on inpatient admission for respiratory illness was independent of the child's birth weight, type of feeding, father's education, size of the home, and chronic respiratory disease among adults in the family. The adjusted odds ratios compared with the non-smoking group were 1.17 in families smoking 1.9 cigarettes daily and 1.89 in families smoking 10 or more cigarettes daily. These data suggest that exposure to household cigarette smoke of children in early life increases the risk of severe respiratory illness. PMID- 3089496 TI - Pregnancy in women with Friedreich's ataxia. PMID- 3089497 TI - Ingestion of button batteries: hazards and management. PMID- 3089498 TI - An unusual case of Gardnerella vaginalis septicaemia. PMID- 3089499 TI - Red cell morphology at high altitude. PMID- 3089500 TI - Low concentrations of formaldehyde in bronchial asthma: a study of exposure under controlled conditions. PMID- 3089501 TI - Referral to medical outpatients department at teaching hospitals in Birmingham and Amsterdam. AB - A method of comparing the referral of patients by general practitioners to medical outpatients departments at teaching hospitals in Amsterdam and Birmingham was devised. This was applied to 89 referral letters to medical specialists at the Free University Medical School Policlinic in Amsterdam and to 88 referral letters to clinics at Birmingham University Medical School, UK. The standards of referral were lower in the Netherlands than in Britain, and this may be related to differences in the health care systems, in the culture, or in the organisation of general practice. The delay between the general practitioner's referral and the consultation to the outpatient department was four times greater in Britain than in the Netherlands. PMID- 3089502 TI - Diagnosing cancer in general practice: from suspicion to certainty. AB - Three hundred and eighty two patients who were suspected of having cancer by general practitioners were followed up for up to two years until the suspicion was either confirmed or rejected; 7014 patients who were not suspected of having a malignancy served as the control group. Less than every tenth suspicion proved correct. The general practitioner's assessment of the strength of suspicion of cancer was the best predictor of outcome in the suspected patients. The incidence of cancer among the unsuspected patients did not differ from the total incidence of cancer in the study area. The patient's fear of cancer was an important predictor of a malignancy. A higher proportion of patients who consulted for non symptomatic reasons than for symptomatic reasons was reported to have a malignancy. No single symptom had a strong predictive value for cancer. The predictive value of a palpable lump or tumour was 2.5%. PMID- 3089503 TI - Making dysphoria a happy experience. PMID- 3089504 TI - "Homeward bound": a minimal care rehabilitation unit. AB - A 20 bed minimal care rehabilitation unit was set up by Newham District Health Authority in a small hospital originally scheduled for closure when a new district general hospital was opened. During the first year 114 patients were admitted (throughput 5.7), with a median length of stay of 30 days; in the second year 173 patients were admitted (throughput 8.65) with a median length of stay of 28.5 days. The cost per inpatient day was less than that of an inpatient day at the district's long stay geriatric unit. Before the unit opened 24% of the acute beds had been occupied for more than six weeks, whereas two years later only 6% of the acute beds were occupied for such a period. PMID- 3089505 TI - Lessons from the outbreak of food poisoning at Stanley Royd Hospital: what are health authorities doing now? AB - The committee of inquiry into the outbreak of food poisoning at Stanley Royd Hospital identified serious deficiencies in the management of the outbreak and urged all health authorities to learn from the incident and prepare adequate plans for dealing with any future outbreaks. A survey of district health authorities in England showed that most authorities do not yet have a written plan or that their plans are incomplete and inadequate. The appreciable resistance to such planning suggests that most health authorities would be unable to deal with outbreaks of food poisoning effectively and efficiently. PMID- 3089506 TI - Health for the people or cash for the clever? PMID- 3089507 TI - Report from the PHLS Communicable Disease Surveillance Centre. PMID- 3089508 TI - Manpower and training. PMID- 3089509 TI - Halothane and the liver. PMID- 3089510 TI - Postresuscitation care. PMID- 3089511 TI - Severity scoring in intensive care. PMID- 3089512 TI - QALYs or short straws. PMID- 3089514 TI - The need for a public health alliance. PMID- 3089513 TI - Why do patients still die from paracetamol poisoning? PMID- 3089516 TI - AIDS: act now, don't pay later. PMID- 3089515 TI - Lymphostatic disorders. PMID- 3089517 TI - Unwanted hair. PMID- 3089518 TI - Lies, damned lies, and suppressed statistics. PMID- 3089519 TI - The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure. AB - Day and night urine volume, morning and evening body weight, and supine and sitting blood pressure were measured in five patients with chronic autonomic failure who were not receiving treatment with drugs. All had nocturnal polyuria, overnight weight loss, and a pronounced postural fall in blood pressure, with lowest levels in the morning. Desmopressin (2-4 micrograms given intramuscularly at 8 pm) reduced nocturnal polyuria, diminished overnight weight loss, raised supine blood pressure, and reduced the postural fall, especially in the morning, when patients were often at their worst. Desmopressin may be a useful alternative to, or may supplement, other forms of treatment in some patients with autonomic failure. PMID- 3089520 TI - Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. AB - Polycystic ovaries were defined with ultrasound imaging in a series of 173 women who presented to a gynaecological endocrine clinic with anovulation or hirsutism. Polycystic ovaries were found in 26% of women with amenorrhoea, 87% with oligomenorrhoea, and 92% with idiopathic hirsutism--that is, hirsutism but with regular menstrual cycles. Fewer than half the anovulatory patients with polycystic ovaries were hirsute, but in 93% of cases there was at least one endocrine abnormality to support the diagnosis of polycystic ovaries--that is, raised serum concentrations of luteinising hormone, raised luteinising hormone: follicle stimulating hormone ratio, or raised serum concentrations of testosterone or androstenedione. This study shows that polycystic ovaries, as defined by pelvic ultrasound, are very common in anovulatory women (57% of cases) and are not necessarily associated with hirsutism or a raised serum luteinising hormone concentration. Most women with hirsutism and regular menses have polycystic ovaries so that the term "idiopathic" hirsutism no longer seems appropriate. PMID- 3089521 TI - Does informed consent influence therapeutic outcome? A clinical trial of the hypnotic activity of placebo in patients admitted to hospital. AB - To examine whether written informed consent might influence the results of clinical trials the effect of placebo when given with or without informed consent to patients suffering from insomnia was studied. The study was a single blind observer blinded trial, and patients were paired according to sex, age, and hospital environment. Randomisation assigned the first patient of each pair to the control group (without informed consent) or the group to give informed consent. Of the 56 patients, 26 refused to give informed consent, and the age and sex distribution of these differed significantly (p less than 0.02) from the 30 pairs of patients ultimately enrolled into the study. In this "biased" sample, the hypnotic activity of placebo was significantly higher in the control group (p less than 0.05). It is concluded that the informed consent procedure biases the results of clinical trials and might affect their general applicability. PMID- 3089522 TI - Use of a visual analogue scale in the diagnosis of urinary incontinence. PMID- 3089523 TI - A case of scurvy. PMID- 3089524 TI - Diabetic renal disease: differences between Asian and white patients. PMID- 3089525 TI - Awareness and use of glucagon in diabetics treated with insulin. PMID- 3089526 TI - The "last joint" syndrome in ankylosing spondylitis. PMID- 3089527 TI - Publicising patient participation groups. PMID- 3089528 TI - Medical housing "lines". AB - General practitioners are often asked for medical certificates (housing "lines") by applicants for council housing who claim to have medical problems requiring housing priority. The results of a survey by questionnaire showed that general practitioners in Edinburgh do not know how the housing system works and that they seem to overestimate their patients' chances of obtaining suitable council housing. General practitioners need to know how the housing system works, and communication between general practitioners and housing departments should be improved. A comparison was also made between the number of medical points awarded by a community medicine specialist and a group of general practitioners who had written housing "lines" for their patients. The general practitioners tended to award more points than the specialist. Social priority for housing should be recognised as an independent factor and a new category of top social priority added. PMID- 3089529 TI - Usefulness of nutritional indices and classifications in predicting death of malnourished children. AB - The usefulness of nutritional indices and classifications in predicting the death of children under 5 years old was evaluated by comparing measurements of 34 children with diarrhoea who died in a Dhaka hospital with those of 318 patients who were discharged in a satisfactory condition. In a logistic regression analysis mid-upper arm circumference was found to be as effective as other nutritional indices in predicting death. Combinations of different indices did not improve the prediction. Arm circumference might be preferable to more complex criteria for predicting the death of malnourished children. PMID- 3089530 TI - Incarcerated inguinal hernia in infants. PMID- 3089531 TI - Parkinson's disease. PMID- 3089532 TI - Informed consent. PMID- 3089533 TI - Neurological complications of coronary artery bypass graft surgery. PMID- 3089534 TI - Opiate withdrawal: inpatient versus outpatient programmes. PMID- 3089535 TI - Transcutaneous oxygen tension during exercise in patients with claudication. PMID- 3089536 TI - Neurotensin immunoreactivity in the human cingulate gyrus, hippocampal subiculum and mammillary bodies. Its potential role in memory processing. AB - Neurotensin immunoreactive neurons comprise the majority of large perikarya in the human subiculum and project axons to the alveus, fimbria, fornix and neuropil of the mammillary bodies. These regions are prominently involved in conditions such as Wernicke's and Alzheimer's disease in which memory is impaired. Neurotensin has potential significance as a peptide in a human brain circuit which may serve a role in memory processing. PMID- 3089537 TI - A neurotensin-immunoreactive pathway from the subiculum to the mammillary body in the rat. AB - The existence of a neurotensin-like immunoreactive (NT-IR) pathway from the subiculum to the mammillary body was demonstrated in very young rats using immunocytochemistry, knife cut, electric lesion and retrograde tracer techniques. Unilateral hemitransection of the dorsal fornix caused a marked reduction of NT IR fibers in the ipsilateral mammillary body. Unilateral electric lesion of the subiculum also resulted in ipsilateral reduction of NT-IR fibers in the mammillary body. Biotin-wheat germ agglutinin (B-WGA), injected into the mammillary body, labeled neurons in the ipsilateral subiculum which were shown by double staining to have NT-IR cytoplasm. These findings demonstrate the presence of a major NT-IR fiber pathway from the subiculum to the mammillary body via the fornix. PMID- 3089538 TI - The hypothalamo-infundibular growth hormone-releasing hormone (GH-RH) system of the rat. AB - Two to 10 days after complete unilateral surgical isolation of the medial basal hypothalamus (MBH) or 3 months following neonatal monosodium glutamate (MSG) treatment, the presence of growth hormone-releasing hormone (GH-RH) immunoreactive neuronal structures was studied in rats using vibratome sections and GH-RH immunocytochemistry. Neonatal MSG treatment resulted in a dramatic decrease of GH-RH immunoreactivity in the median eminence (ME), but not complete disappearance as reported earlier. Unilateral complete deafferentation of the MBH caused only a slight decrease in GH-RH immunostaining in the posterior regions of the ipsilateral median eminence (ME). At this level GH-RH accumulation was observed in scattered transected fibers lateral to the cut, outside of the MBH. Our findings indicate that the arcuate nucleus is the major source of GH-RH immunoreactive structures in the ME. Although, however, in very small numbers, the existence of other sources of GH-RH terminals cannot be excluded. PMID- 3089539 TI - Involvement of monoamine oxidase enzymes in the action of 1-methyl-4-phenyl 1,2,5,6-tetrahydropyridine, a selective neurotoxin, in the squirrel monkey: binding and biochemical studies. AB - 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is a new neurotoxin that causes degeneration of the dopaminergic nigrostriatal neurons and induces a Parkinson-like state in several species, including humans and monkeys. The present study was designed to better characterize the properties of [3H]MPTP binding sites and to evaluate the interaction of MPTP with the oxidation of dopamine by monoamine oxidase (MAO) in an animal species (Saimiri Sciureus) shown to be lesioned by MPTP. Our data confirm the presence of high affinity and saturable binding sites for [3H]MPTP in the squirrel monkey. Specific binding with analogous characteristics also occurs in peripheral tissues. Various substances failed to inhibit the [3H]MPTP binding, whereas only MAO inhibitors (MAOI) were able to antagonize this binding to brain and peripheral tissues. In particular, deprenyl, a selective inhibitor of MAO type B enzyme, was relatively more potent as a displacer of [3H]MPTP from its binding sites both in brain and in peripheral tissues. Our results further suggest a correspondence between [3H]MPTP sites and MAO, particularly MAO-B, in monkey brain. Moreover, our data show that the oxidative deamination of dopamine is inhibited by MPTP in vitro. In conclusion, these data are consistent with the hypothesis of the involvement of MAO in the neurotoxic effects of MPTP, even though further experiments are necessary to better clarify the molecular mechanism of MPTP neurotoxicity. PMID- 3089540 TI - A monoclonal antibody to mammalian neurofilament protein stains somata and dendrites in gymnotid fish. AB - Monoclonal antibody N210 (mabN210) recognizes the 210 kdalton neurofilament protein in mammals and gives characteristic immunocytochemical staining of neurofilament-rich processes. For example, in the cerebellum it recognizes myelinated axons and the calyx formed by basket cell axon collaterals. The distribution of mabN210 immunoreactivity was studied in the gymnotid brain (Apteronotus albifrons). In contrast to the mammalian distribution, mabN210 immunoreactivity was not found in most axons of the gymnotid brain. Instead, deposits of reaction product were present in the somata and dendrites of most neurons and were especially dense in those neurons with extensive dendritic trees, the Purkinje cells, pyramidal cells of the electrosensory lateral line lobe, the crest cells of the nucleus medialis and the pyramidal cells of the tectum. Electrosensory lateral line lobe pyramidal cells are known to contain few, if any, neurofilaments in their dendrites. Western blots of whole gymnotid brain proteins demonstrated that mabN210 recognizes two polypeptides apparent molecular weights 60 and 19 kdaltons. These proteins are thus antigenically similar to neurofilament protein and their expression in the gymnotid brain may be related to the peculiar dendritic branching pattern of Purkinje cells and similar cell types. PMID- 3089542 TI - Thyrotropin-releasing hormone-induced changes in electroencephalographic and vagal activity in the cross-circulated brain of the rat. AB - The effects of centrally administered thyrotropin-releasing hormone (TRH) on vagal efferent and cortical electroencephalographic (EEG) activity were assessed in rat brains which were functionally isolated from the body trunk and maintained via cross-circulation. Upon withdrawal of inputs from the trunk, cervical vagal activity was markedly attenuated. The decreased activity was partially restored by TRH with a latent period of a few minutes. On the other hand, TRH immediately but transiently augmented the fast waves of the EEG. The change in brain activity produced by TRH appears to simulate the state which makes possible the generation of vagal efferent activity even though inputs from the body trunk are withdrawn. PMID- 3089541 TI - Chronic immunization of endogenous thyrotrophin-releasing hormone (TRH) in brain alters the behavioural response to pentobarbital and a TRH analogue. AB - Rats were infused with purified thyrotrophin-releasing hormone (TRH) anti-serum i.c.v. for two weeks and the reversal of pentobarbital-induced anaesthesia, hypothermia and respiratory depression by central administration of a TRH analogue (CG 3509) was measured. After antibody infusion the anaesthesia time was more than doubled but the responses to CG 3509 were increased, suggesting a role for endogenous TRH in arousal mechanisms which is sensitized following chronic immunological blockade. PMID- 3089543 TI - [Detection of antibodies to viruses causing hemorrhagic fever associated with a renal syndrome]. PMID- 3089545 TI - Progress against cancer? A broader view. PMID- 3089544 TI - The "atypical" Papanicolaou smear. AB - Optimal management of the patient with the atypical smear requires a narrative description of the findings as well as frequent personal communication with the cytopathologist. When the cytologic abnormality suggests the possibility of an underlying early or poorly formed neoplastic lesion, colposcopy is recommended. A definitive histopathologic diagnosis can be obtained with a colposcopically directed biopsy, and any preinvasive lesions can usually be treated with excellent results on an outpatient basis with cryotherapy or laser therapy. PMID- 3089546 TI - Current concepts in the control of carcinoma of the endometrium. AB - With respect to the most efficient approach to the diagnosis and treatment of carcinoma of the endometrium, the recognition of women at high risk can reduce this disease to a minimum and possibly eradicate much of the resulting mortality. Such an approach depends on the following factors: Recognition of the menopause as a time of life when high-risk patients may be identified. Recognition of adenomatous hyperplasia as a precursor of invasive endometrial cancer. Further research into the technology of obtaining suitable samples in menopausal women on an ambulatory basis without anesthesia is indicated as a search for efficient screening. Until such research yields new methods, however, recognition of the high-risk menopausal women through histologic sampling at menopause, with or without dysfunctional bleeding, can serve well. The modern FIGO staging formula shows the order of clinical virulence of any endometrial cancer and allows individualization of treatment in a manner that prevents overtreatment of those with less aggressive tumors and undertreatment of those with highly virulent tumors. Overtreatment causes an excess of complications, and undertreatment leads to a lower rate of cure than might be obtained by more radical treatment. Such individualization of treatment allows recognition of the appropriate place for surgical and/or radiotherapeutic treatment and the combinations that are most appropriate for the particular patient. Individualization also encourages the development of new chemotherapeutic agents and more efficient use of those now existing. Hormonal treatment is indicated for several categories of perimenopausal or postmenopausal patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089547 TI - Transfusion therapy. PMID- 3089548 TI - Pap smear. PMID- 3089549 TI - Cancer in elderly blacks. PMID- 3089550 TI - Sarcocystosis, toxoplasmosis, and cryptosporidiosis in cattle. PMID- 3089551 TI - Epidemiology and control of coccidia in goats. PMID- 3089552 TI - The role of serum concentrations of sex steroids and bone turnover in the development and occurrence of postmenopausal osteoporosis. AB - It has been debated whether postmenopausal osteoporosis is characterized by high or low bone turnover and whether circulating levels of sex steroids contribute to the occurrence of osteoporotic fractures. We examined 154 70-year-old women with or without osteoporotic fractures, and 178 early postmenopausal women with a "rapid" or a "slow" bone loss. In all participants, we determined markers of bone formation (serum alkaline phosphatase (AP) and serum bone Gla protein (BGP)), markers of bone resorption (fasting urinary calcium/creatinine (FU Ca/Cr) and hydroxyproline/creatinine (FU Hpr/Cr)), and serum estrone (E1), estradiol (E2), androstenedione (A), and fat mass. The 70-year-old women with osteoporotic fractures had significantly elevated AP (P less than 0.001), BGP (P less than 0.001), and FU Hpr/Cr (P less than 0.001) compared with the group without fractures. In the group of early postmenopausal women, the "rapid" bone losers had significantly increased FU Hpr/Cr (P less than 0.001) and FU Ca/Cr (P less than 0.001). E1, E2, A, and the fat mass did not differ in the groups with and without osteoporotic fractures, whereas the "rapid" bone losers had significantly lower E1 (P less than 0.05), E2 (P less than 0.05), and fat mass (P less than 0.01) than the "slow" bone losers. It is concluded that patients with manifest osteoporosis and early postmenopausal women with a rapid bone loss have increased biochemical markers of bone turnover. Moreover, the present study demonstrates that early postmenopausal women with an "excessive" bone loss have significantly decreased serum estrogens, whereas it is not possible to detect low estrogens in women with osteoporotic fractures. PMID- 3089553 TI - Bone remodeling during the development of osteoporosis in paraplegia. AB - Osteoporosis developing during the first weeks after the onset of traumatic paraplegia was studied with cortical and cancellous samples of iliac crest and tibia of 14 patients, and compared to normals. We used a procedure of bone particle fractionation (according to degree of mineralization) that allowed us to establish a profile reflecting the metabolic remodeling of bone and to analyze the organic matrix of the newly synthesized tissue. In paraplegics, we observed a large increase in the proportion of little calcified bone in the cortical as well as in the cancellous bone. Based on amino acid analyses, we found a decreased number of hydroxyproline residues in the newly synthesized organic matrix from paraplegia bone resulting either from an alteration of the prolyl hydroxylation or from the presence of an excess of noncollagen polypeptides. These results, together with previously published data reporting increased urinary hydroxyproline and calcium kinetic parameters, suggest an enhanced rate of skeletal remodeling in acute paraplegia. When investigated 2 years after injury, the patterns of distribution approach that of normal subjects. PMID- 3089554 TI - Effect of a long-term treatment with 1,25-dihydroxyvitamin D3 on osteocalcin in postmenopausal osteoporosis. AB - Serum bone Gla-protein (BGP or osteocalcin) was measured in 25 women with histologically confirmed postmenopausal osteoporosis before and during long-term treatment with 1 microgram/day of 1,25-dihydroxyvitamin D3(1,25(OH)2D3). Basal serum BGP was significantly lower in osteoporotic women (3.8 +/- 1.4 ng/ml) than in age-matched controls (6.8 +/- 2.0 ng/ml). During 1,25(OH)2D3 therapy serum BGP increased so that the mean of the values observed on treatment (4.8 +/- 1.5) was significantly higher than the mean basal value. It is known that BGP synthesis is stimulated by 1,25(OH)2D3 and that serum BGP is a specific marker of bone formation; therefore, it is possible that the low basal levels of osteocalcin we observed were related to the low serum 1,25(OH)2D concentrations reported in osteoporotic women and that the increase in BGP levels observed under 1,25(OH)2D3 treatment was a consequence of osteoblast stimulation. PMID- 3089555 TI - Water on apatites. AB - Adsorption of water was studied gravimetrically at 23 degrees C in an open system at several relative humidities on a variety of apatitic calcium phosphates including enamel, deproteinized enamel, and bone mineral. The amount of adsorbed water increases linearly with the surface areas of the synthetic apatites and does not appear very sensitive to calcium to phosphorus ratio of the apatites. The adsorption results correlate very well up to about two monolayers with a conventionally determined isotherm. Higher uptake of water even by "deproteinized" enamel or bone may be due to the presence of pore structure and incompletely removed organic matter. PMID- 3089556 TI - Human calcitonin gene-related peptide possesses weak inhibitory potency of bone resorption in vitro. AB - Synthetic human calcitonin gene-related peptide (CGRP) was examined for the action on the bone in vitro. Human CGRP inhibited bone resorption stimulated by both human parathyroid hormone and basal. The mode of inhibitory action of human CGRP seemed to be similar to that of calcitonin and the relative potency of human CGRP to inhibit bone resorption is one five-hundredth of that of human calcitonin. Thus, a novel pharmacological action of CGRP was demonstrated. PMID- 3089557 TI - Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat. AB - Three new bisphosphonates of various chain length, namely, 4-amino-1 hydroxybutylidene-1,1-bisphosphonate (AHBuBP), 5-amino-1-hydroxypentylidene-1,1 bisphosphonate (AHPeBP), and 6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) were compared with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), and dichloromethylene bisphosphonate as to their effect on metaphyseal bone remodeling in the rat. The parameters assessed were growth in length, mineralization, metaphyseal density, mean trabecular diameter, and number of trabeculae. Both metaphyseal density, an index of metaphyseal Ca balance, and number of trabeculae, an index of bone resorption, showed the following sequence of potency: AHBuBP greater than AHPrBP = AHPeBP = AHHexBP greater than Cl2MBP. All compounds decreased trabecular diameter somewhat, an index of bone formation, with AHBuBP decreasing the least. AHBuBP and possibly AHHexBP appear to be interesting new bisphosphonates for future clinical use. PMID- 3089558 TI - Casein phosphopeptides: their effect on calcification of in vitro cultured embryonic rat bone. AB - The effect of casein phosphopeptides (CPP) and enzymatically dephosphorylated, otherwise identical peptides (DPP) on Ca solubility and mineralization was studied in an in vitro model. The model consisted of explanted embryonic rat bone rudiments (femora, tibiae, and metatarsals), cultured in Bigger's medium at two different concentrations of total calcium (1.78 mM and 3.24 mM). The medium enabled growth of the explants, but minor or no mineralization took place during a culture period of 11 days. The medium was unstable with respect to Ca solubility, and measurements with a selective electrode showed that during most of the time the actual concentration of soluble, ionic Ca2+ was not higher than about 0.7 mM. CPP added at a concentration of 10 mg/100 ml of the medium vastly improved Ca-solubility under culture conditions. The mean concentration of soluble, ionic Ca2+ in the presence of the peptides was 1.4 mM at total calcium = 1.78 mM and 2.3 mM at the higher total calcium level (3.24 mM). Rudiments cultured in the presence of CPP showed impressive increases in calcification of their diaphyseal area. This progress in mineralization was quantitatively assayed by measuring the projected dark diaphyseal area at the beginning and at the end of the culture period. It was also verified by histological sections of the rudiments. DDP did not enhance Ca solubility of the culture medium, nor did explants cultured in the presence of 10 mg/100 ml of DPP show any significant progress in mineralization. This indicated that the activity of CPP was dependent on the presence of serine-linked phosphate groups. PMID- 3089559 TI - Studies in a patient with tumor-induced hypophosphatemic osteomalacia. AB - A 7-year study of a patient with tumor (hemangiopericytoma)-induced hypophosphatemic osteomalacia (TIO) is presented, and the findings are in keeping with the depressed tubular reabsorption of phosphate and low 1,25(OH)2 vitamin D levels seen in other studies. Despite normalization of 1,25(OH)2 vitamin D levels with pharmacologic doses of vitamin D2, there was no discernible effect on serum phosphorus levels. Also, despite hypercalcemia induced by pharmacologic doses of vitamin D2, serum parathyroid hormone levels were persistently elevated, and gradually returned to subnormal levels after removal of the tumor. Following removal of the tumor, there was a rapid increase of the 1,25(OH)2 vitamin D levels to supraphysiologic levels, prompt appropriate increase in tubular reabsorption of phosphate levels, and symptomatic improvement in the osteomalacia. Speculations on the physiologic and pathophysiologic role of the putative hormone(s) produced by the tumors associated with this syndrome are presented. PMID- 3089560 TI - Resorption of the mouse incisor after the application of cold to the periodontal attachment apparatus. AB - In order to study in detail the processes leading to the resorption and ankylosis of teeth after trauma, the effects of cold application on the periodontal tissues were studied in the mouse. Liquid nitrogen was applied locally to the outer surface of the lower jaw which resulted in a freezing of the incisor and its surrounding tissues. The healing processes in the damaged periodontal ligament and the accompanying phenomena of ankylosis and dental root resorption were investigated histologically at both the light and electron microscopic levels. As a result of cold application, the cells in the periodontal ligament were killed. After a few days, the ligament started to be repopulated with cells like fibroblasts and macrophages. From 3 days on, mineral crystallites were deposited along the cementum covering the lingual, mesial, and lateral surfaces of the incisor, finally resulting in a 4-6 micron thick layer. During the period of 7-12 days following cold application, this layer of mineralized material started to be phagocytosed and degraded, presumably by mononuclear cells. Finally, extensive root resorption and some ankylosis between the tooth and the alveolar bone were observed. In the resorbed areas, cells were seen which could not be distinguished from osteoclasts. In some instances, their ruffled border was in close apposition with each of the three mineralized tissues--dentin, cementum, and alveolar bone. It is hypothesized that the deposition and subsequent phagocytosis of mineralized material along the root surface may be an important factor in the initiation of dental root resorption. PMID- 3089561 TI - Histomorphometric study of trabecular channels in normal iliac bone. AB - Cancellous bone channels in the normal iliac crest have been studied histologically and by histomorphometry, and their biological role has been considered. Eighty percent of trabecular channels were typical osteons with the same structural and remodeling features as cortical osteons. The similarity of osteons in these two locations was corroborated by the comparability of morphometric features. The points of difference between osteons in the two types of bone were irregular configurations of trabecular osteons and marrow cells in the central canal in some. Since the number of trabecular osteons decreases with age, and since active trabecular resorption cavities were few in number, it is unlikely that additional osteons are formed in normal bone after the active modeling phase of bone growth. It is improbable that they make a significant contribution to bone remodeling since their number decreases with age, and since the available surface of trabecular channels for remodeling is extremely small. However, it is probable that they aid the intraosseous microcirculation and mineral exchange in thick trabecula and bifurcations, where they are mainly located. The demarcation curves at the 95% confidence interval, which suggest the normal range for numbers of channels, was calculated from the scatter diagram against bone area. PMID- 3089563 TI - Comparison of the mechanisms of bone resorption induced by 1 alpha,25 dihydroxyvitamin D3 and lipopolysaccharides. AB - The mechanisms of increase in bone resorption induced by 1 alpha,25 dihydroxyvitamin D3 [1 alpha,25(OH)2D3] and bacterial lipopolysaccharides (LPS) were compared in an in vitro dead bone assay and a living bone assay. 1 alpha,25(OH)2D3 at concentrations of 0.05-5 ng/ml dose-dependently enhanced the ability of alveolar macrophages to release 45Ca from prelabeled dead bone particles (dead bone assay). In addition, the vitamin promoted fusion of the macrophages to form multinucleated cells and also enhanced glucose consumption, a marker of activation of macrophages. LPS at 0.05-5 micrograms/ml similarly enhanced the release of 45Ca from the dead bone particles and glucose consumption by alveolar macrophages, but it did not induce fusion of the cells at any concentration. Both 1 alpha,25(OH)2D3 and LPS dose-dependently stimulated the release of 45Ca from fetal mouse calvaria prelabeled with 45Ca (living bone assay). Compared to control bone, there were several times as many osteoclasts per given length of trabecular bone surface in calvaria treated for 5 days with either 5 ng/ml of 1 alpha,25(OH)2D3 or 5 micrograms/ml of LPS. Indomethacin (10( 5) M) completely inhibited the LPD-induced increase of osteoclasts, but not the 1 alpha,25(OH)2D3-induced increase. These results suggest that 1 alpha,25(OH)2D3 and LPS similarly stimulate bone resorption by activating macrophages as well as by promoting fusion of precursor cells to form multinucleated cells. 1 alpha,25(OH)2D3 induced formation of multinucleated cells with bone-resorbing activity directly, whereas LPS appeared to induce multinucleated cells through prostaglandin synthesis by some other types of cells present in living bone tissues. PMID- 3089562 TI - Bone in the marmoset: a resemblance to vitamin D-dependent rickets, type II. AB - The common marmoset, a New World monkey, requires a large amount of vitamin D3 to maintain its normal growth. This monkey is reported to have an end-organ resistance to 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3). In this study, the bone morphology of marmosets fed a high vitamin D3 diet (intake of vitamin D3, 110 IU/day/100 g of body weight) was compared by X-ray and histological examinations with that of rhesus monkeys (Old World monkey) fed a normal diet (intake of vitamin D3, 5 IU/day/100 g of body weight). Three of 20 marmosets were found by X-ray examination to have osteomalacic changes in their bones despite the high daily intake of vitamin D3, whereas none of the 5 rhesus monkeys showed any signs of osteomalacia. Osteomalacic marmosets had distinct increases in osteoid surface, relative osteoid volume, and active osteoclastic bone resorption, whereas non-osteomalacic marmosets had no increase in osteoid tissues in their bones. None of the marmosets, either osteomalacic or non-osteomalacic, was hypercalcemic despite the extremely high circulating levels of 1 alpha,25(OH)2D3. However, the serum 25-hydroxyvitamin D3 (25OHD3) and 24R,25 dihydroxyvitamin D3 (24R,25(OH)2D3) levels were significantly lower in the osteomalacic than in the non-osteomalacic marmosets. These results suggest that the marmoset is likely to exhibit osteomalacic bone changes despite the high daily intake of vitamin D3. These changes resemble those in vitamin D-dependent rickets, type II. PMID- 3089565 TI - The concentration of calcium and phosphorus in trabecular bone from the iliac crest. AB - The concentrations of calcium and phosphorus were determined in central parts of bone trabeculae in the human iliac crest by means of an energy dispersive microanalysis technique. Two age groups, each consisting of six suddenly diseased male subjects, were investigated. It was found that the concentrations of calcium and phosphorus did not differ between young and old men. The obtained mean values were fairly alike and determined to 40 and 17 weight %, respectively. PMID- 3089564 TI - Formation of calcifying matrix by osteosarcoma cells in diffusion chambers in vivo. AB - The potential of clonal rat osteosarcoma (ROS) cell lines to form mineralized matrices was assessed in diffusion chambers in vivo. Diffusion chambers were inoculated with osteoblastic (ROS 17/2 and its subclone ROS 17/2.8) and non osteoblastic (ROS 24/1) clonal lines and implanted either intraperitoneally into athymic mice or subcutaneously into syngeneic ACI rats. Control chamber cultures of rabbit marrow or spleen cells were also incubated in athymic mice. Light and electron microscopy of chambers with ROS 17/2 and ROS 17/2.8 cells revealed production of mineralized matrices typical of osteosarcoma and characterized by abundance of collagen fibrils and associated mineralizing nodules. ROS 24/1 cells produced similar collagenous matrices, but these were devoid of mineral. The present experiments, carried out independently in two different laboratories, demonstrate the potential of ROS cells to produce a mineralized matrix. This corroborates previous studies on other osteoblastic features of these cell lines. PMID- 3089566 TI - Disopyramide phosphate effects on slow and depressed fast responses. AB - We studied the effects of disopyramide phosphate on explanted neonatal rat ventricle cells exhibiting depressed fast responses or naturally occurring slow response action potentials together with automatic activity. Disopyramide suppressed the spontaneous activity at a concentration of 2.5 micrograms/mL with a half-maximal value of 10 micrograms/mL. Before spontaneous activity was lost, there was an increase in beating rate possibly related to membrane depolarization. In depressed fast and slow response action potentials there was an increase in action potential duration (APD) which was consistently found both at the level of the plateau and at 90% repolarization. Comparison of the APD increase observed after disopyramide treatment and that after exposure to 20 mM tetraethylammonium suggested a block of a potassium conductance as a possible cause underlying the change in APD. The Vmax values of the depressed fast response decreased at constant membrane potential and this was attributed to the local anesthetic effect of the drug. In addition, we report two novel findings: (i) a decrease of Vmax of the slow response action potentials which may be secondary to membrane depolarization, and (ii) an increase in the duration of slow action potentials, possibly caused by inhibition of a potassium conductance. PMID- 3089567 TI - Cadmium transport, resistance, and toxicity in bacteria, algae, and fungi. AB - Cadmium is an important environmental pollutant and a potent toxicant to bacteria, algae, and fungi. Mechanisms of Cd toxicity and resistance are variable, depending on the organism. It is very clear that the form of the metal and the environment it is studied in, play an important role in how Cd exerts its effect and how the organism(s) responds. A wide range of Cd concentrations have been used to designate resistance in organisms. To date, no concentration has been specified that is applicable to all species studied under standardized conditions. Cadmium exerts its toxic effect(s) over a wide range of concentrations. In most cases, algae and cyanobacteria are the most sensitive organisms, whereas bacteria and fungi appear to be more resistant. In some bacteria, plasmid-encoded resistance can lead to reduced Cd2+ uptake. However, some Gram-negative bacteria without plasmids are just as resistant to Cd as are bacteria containing plasmids encoding for Cd resistance. According to Silver and Misra (1984), there is no evidence for enzymatic or chemical transformations associated with Cd resistance. Insufficient information is available on the genetics of Cd uptake and resistance in cyanobacteria and algae. Mechanisms remain largely unknown at this point in time. Cadmium is toxic to these organisms, causing severe inhibition of such physiological processes as growth, photosynthesis, and nitrogen fixation at concentrations less than 2 ppm, and often in the ppb range (Tables 2 and 3). Cadmium also causes pronounced morphological aberrations in these organisms, which are probably related to deleterious effects on cell division. This may be direct or indirect, as a result of Cd effects on protein synthesis and cellular organelles such as mitochondria and chloroplasts. Cadmium is accumulated internally in algae (Table 4) as a result of a two-phase uptake process. The first phase involves a rapid physicochemical adsorption of Cd onto cell wall binding sites, which are probably proteins and (or) polysaccharides. This is followed by a lag period and then a slow, steady intracellular uptake. This latter phase is energy dependent and may involve transport systems used to accumulate other divalent cations, such as Mn2+ and Ca2+. Some data indicate that Cd resistance, and possibly uptake, in algae and cyanobacteria is controlled by a plasmid-encoded gene(s). Although considerable information is available on Cd toxicity to, and uptake in fungi, further work is clearly needed in several areas. There is little information about Cd uptake by filamentous fungi, and even in yeasts, information on the specificity, kinetics, and mechanisms of Cd uptake is limited.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3089568 TI - alpha-Aminoadipate pool concentration and penicillin biosynthesis in strains of Penicillium chrysogenum. AB - Intracellular amino acid pools in four Penicillium chrysogenum strains, which differed in their ability to produce penicillin, were determined under conditions supporting growth without penicillin production and under conditions supporting penicillin production. A significant correlation between the rate of penicillin production and the intracellular concentration of alpha-aminoadipate was observed, which was not shown with any other amino acid in the pool. In replacement cultivation, penicillin production was stimulated by alpha aminoadipate, but not by valine or cysteine. Exogenously added alpha-aminoadipate (2 or 3 mM) maximally stimulated penicillin synthesis in two strains of different productivity. Under these conditions intracellular concentrations of alpha aminoadipate were comparable in the two strains in spite of the higher rate of penicillin production in the more productive strain. Results suggest that the lower penicillin titre of strain Q 176 is due to at least two factors: (i) the intracellular concentration of alpha-aminoadipate is insufficient to allow saturation of any enzyme which is rate limiting in the conversion of alpha aminoadipate to penicillin and (ii) the level of an enzyme, which is rate limiting in the conversion of alpha-aminoadipate to penicillin, is lower in Q 176 (relative to strain D6/1014/A). Results suggest that the intracellular concentration of alpha-aminoadipate in strain D6/1014/A is sufficiently high to allow saturation of the rate-limiting penicillin biosynthetic enzyme in that strain. The basis of further correlation of intracellular alpha-aminoadipate concentration and penicillin titre among strains D6/1014/A, P2, and 389/3, the three highest penicillin producers studied here, remains to be established.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089569 TI - C-390 as sole selective agent for isolation of Pseudomonas aeruginosa from hospital waste water. AB - Pseudomonas aeruginosa was recovered (in numbers ranging from 10(2) to 10(5) colony-forming units per millilitre) from heavily contaminated hospital waste water when grown at 41.5 degrees C on a differential medium agar containing 9 chloro-9-(4-diethylaminophenyl)-10-phenylacridan (C-390) at a final concentration of 30 micrograms/mL. The medium appeared to be highly selective for P. aeruginosa with 95-100% of all colonies isolated from four different hospital waste waters being identified as P. aeruginosa. Many strains of P. aeruginosa isolated from hospital waste waters failed to hydrolyse casein when grown on skim milk agar and this medium appeared to restrict pigment production to only pyoverdin (detectable only under ultraviolet light). However, most strains were capable of casein hydrolysis when grown on a modified skim milk medium. PMID- 3089570 TI - Inhibition of L-lysine uptake by alpha-methyl lysine in Escherichia coli and Bacillus sphaericus. AB - alpha-Methyl lysine was investigated as a potential inhibitor of lysine transport in Escherichia coli and Bacillus sphaericus. At equimolar concentrations, no inhibition was observed in either organism, but at 10X and 100X the lysine concentration, alpha-methyl lysine caused a 20-50% reduction in the initial rate of lysine uptake in both bacteria. A similar inhibitory effect was observed with epsilon-N-methyl lysine on lysine uptake in B. sphaericus, but not in E. coli. alpha-Methyl lysine had a reduced effect on ornithine uptake and no effect on arginine transport in either bacterium. PMID- 3089571 TI - Opsonic activity of antisera to ribosomal vaccine fractions with live and formalinized Pseudomonas aeruginosa. AB - The opsonic capacity of antisera to Pseudomonas aeruginosa ribosomal vaccine fractions was determined by a chemiluminescent technique. Antiserum to a vaccine fraction ("peak A") containing lipopolysaccharide (antiserum A), and antiserum to a vaccine fraction ("peak B"), which did not contain detectable amounts of lipopolysaccharide (antiserum B), were used to opsonify live or formalin-treated bacteria. Polymorphonuclear leukocytes were then stimulated by the opsonified bacteria in the presence of the chemiluminigenic probe, luminol, resulting in the observed chemiluminescence. The data obtained indicated that the antisera had comparable opsonic activity with live (untreated) bacteria. However, antiserum B had far less opsonic activity than did antiserum A when formalinized bacteria were used. Owing to the effects of formaldehyde on protein, these results were interpreted as evidence to suggest that the opsonic activities of the two antisera are dependent on different antigens on the bacterial cell surface. Antiserum A activity is probably dependent on lipopolysaccharide to a great extent, whereas antiserum B activity is most likely dependent primarily on a protein(s). PMID- 3089572 TI - Heart and heart-lung transplantation: the Canadian and world experience from December 1967 to September 1985. AB - By Sept. 1, 1985, 62 centres around the world were identified as having participated in heart transplantation; of these 14 had also performed combined heart-lung transplantation. Between December 1967 and December 1984, 1599 recipients had undergone 1644 transplant procedures. By September 1985, 112 heart lung transplant procedures had been performed in 110 patients. Overall survival at 1 and 3 years respectively, excluding perioperative mortality, averaged 80% and 65%; for heart transplantation alone survival rates were 85% and 75%, respectively. In Canada, of 81 heart and 5 heart-lung transplant procedures that were performed in nine centres between April 1981 and September 1985, 38 heart and 2 heart-lung transplants were carried out in the first 9 months of 1985. Sixty-four of the heart and 2 of the heart-lung transplant recipient were alive from 20 days to 4.42 years postoperatively. PMID- 3089573 TI - Effect of total parenteral nutrition on biliary lipids in neonates. AB - To study the effect of total parenteral nutrition (TPN) on biliary lipids in critically ill neonates, biliary lipid concentrations were determined in 13 neonates before starting TPN, in 8 receiving TPN for up to 2 weeks and in 9 receiving TPN for up to 8 weeks. Bile was very dilute in the 13 neonates not receiving TPN owing to a low concentration of bile acids. In many the bile-acid concentration was below the critical micellar concentration, thus cholesterol in bile was not dissolved. The neonates receiving TPN for up to 2 weeks showed a marked increase in bile-acid content and had levels above the critical micellar concentration. This apparently beneficial effect of TPN disappeared after 2 weeks and neonates who received TPN for 3 to 8 weeks again had bile-acid levels below the critical micellar concentration. Three conclusions may be drawn from this study: (a) in the fasting state before TPN is begun, the cholesterol content of bile relative to phospholipid and bile acids increased in linear fashion during the fasting period; (b) short-term TPN of up to 2 weeks' duration was associated with an increased bile-acid content to levels at which cholesterol could be dissolved; (c) neonates on long-term TPN and no oral intake secrete extremely dilute bile with an insufficient concentration of bile-acid molecules to form micelles to dissolve cholesterol. This finding may explain some of the adverse hepatobiliary changes associated with long-term administration of TPN. PMID- 3089576 TI - The benefit of lithium carbonate adjunct in refractory depression--fact or fiction? AB - Our group attempted to validate previous claims of rapid success with lithium carbonate adjunct therapy in antidepressant-resistant depression. Seven depressed patients volunteered for a study of placebo controlled, double-blind design. During their treatment on general hospital psychiatric wards, these patients received antidepressant medication for a period of at least 21 days. While continuing to receive antidepressant medication after the 21 day period, four of the patients then received lithium carbonate, and three received placebo. This combination pharmacological therapy continued for a 48 hour period. After this time, six of the seven patients showed no significant improvement. The remaining patient, who had received lithium carbonate, improved markedly over the 48 hour period. However, this patient relapsed within one week. A review of the two most extensive studies claiming significant results with the lithium carbonate adjunct therapy was performed. We feel that they, as presented, leave serious doubt as to the validity of their conclusions. We conclude that on the basis of our work up to this point in time and the analysis of previous reports claiming otherwise, no valid evidence exists for a consistent therapeutic effect of lithium carbonate adjunct in antidepressant-resistant depression. It was also found that methodologic contamination necessitated the exclusion of an additional six patients from the double-blind trial. We conclude that in order to objectively examine the rapidly expanding field of biological psychiatry, teaching of clinical staff in basic research procedure should be stressed as a part of routine ward orientation. PMID- 3089574 TI - Growth hormone therapy in Canada: end of one era and beginning of another. AB - This paper reviews the difficulties in diagnosing a true deficiency of growth hormone (GH), the long-term results of therapy, the Canadian experience in treating GH deficiency, including the contributions made by the Medical Research Council's Therapeutic Trial of Human Growth Hormone, and the occurrence of Creutzfeldt-Jakob disease in recipients of GH therapy. It also speculates on potential alternatives to treatment with GH derived from human pituitaries. PMID- 3089575 TI - Acute acalculous cholecystitis in a premature infant treated with parenteral nutrition. PMID- 3089577 TI - The morphology and biologic behavior of human glioblastoma growing in nude mice. AB - Seven human glioblastomas (five small cell glioblastomas [SCG] and two anaplastic astrocytomas with giant cells [AA]) grown in serial passage in BALB/c nude mice and nude rats, were studied histologically and compared to human donor tumors. Four SCG maintained many basic features seen in donor tissue, i.e., cell type, tendency to produce micronecrotic palisading (MNP), high cellularity, numerous mitoses. Significant vascular proliferation was seen only in nude rat hosts of one of the SCG lines transplanted from mice at passage 11. Giant capillaries, cyst formation and hemorrhages were features of large (1.0 cm) heterotransplanted SCG. One SCG altered morphology from first passage, showing an adenoid pattern and mucinous change. Both AA preserved original tissue characteristics in initial passages. Later dedifferentiation occurred with small cells predominating. These small cells were larger and rounder than those of the SCG. Large AA showed central necrosis but rarely MNP, hemorrhages and focal inflammatory infiltrates. PMID- 3089579 TI - Effects of insulin on glucose transporters and metabolic patterns in Harding Passey melanoma cells. AB - The effect of insulin on glucose metabolism through different pathways and the glucose transporters in Harding-Passey melanoma cells have been studied. Glucose was utilized at a rate of 6.9 +/- 2.3 (SD) mumol X g-1 X h-1 with 86% transformed into lactate and pyruvate and only 0.43 and 3% metabolized through the tricarboxylic acid cycle and the pentose phosphate pathway, respectively. Of the total glucose consumed 2% was used in protein synthesis and 2% was used for lipid synthesis. Hexokinase isoenzyme was type I and enolase was present mainly in the alpha gamma hybrid form. The glucose transporters were cytochalasin B sensitive. The number of high affinity cytochalasin B binding sites was 175,000 receptors/cell (about 0.6 pmol/mg protein) and Kd = 1 X 10(-7) M. Insulin increased glucose utilization and lactate production by about 70% and caused a 56% increase in transport without alterations in the Kd of the site. Insulin receptors were quantified by binding assay using 125I-insulin. Kd was 11 X 10(-9) M with the number of receptors calculated as 11,500/cell. Harding-Passey melanoma cells could thus be a useful model to study basic metabolic events and their modulation by hormones or other effectors. PMID- 3089578 TI - Primary malignant lymphoma of the central nervous system. AB - Between 1960 and 1983, 19 patients with primary malignant lymphoma of the central nervous system (CNS) were seen at McGill University Hospitals. The diagnosis was made at autopsy in 3 patients, and by biopsy in 16. Results of treatment were poor. All four patient who underwent surgery alone died within 2 months of diagnosis. Of 12 patients who underwent surgery and postoperative radiotherapy, 11 died between 2 and 56 months (median, 12 months) following diagnosis, and one is alive with disease at 47 months. Patterns of involvement at first recurrence and/or at autopsy were analyzed for 13 patients. Failure at the original site of involvement was unusual after treatment consisting of surgery and radiotherapy. In contrast, failure in the brain at sites other than those originally involved was common in spite of the use of whole brain irradiation. Local leptomeningeal involvement was seen in one patient whose diagnosis was made at autopsy, and cerebral spinal fluid seeding was seen in two additional patients, one within 1 month of diagnosis and one at relapse at 6 months after diagnosis. No patient developed disease outside the CNS. The limitations of current therapy for this disease are discussed, and certain suggestions made regarding the management of future patients with this diagnosis. PMID- 3089580 TI - Inhibition of X-ray or chemical carcinogen-induced neoplastic transformation of C3H10T1/2 fibroblasts by lipopolysaccharides. AB - Oncogenic transformation of mouse 10T 1/2 fibroblasts induced upon exposure to X ray or N-methyl-N'-nitro-N-nitrosoguanidine was suppressed if lipopolysaccharide (LPS) was present in the culture medium. The suppressive effect of LPS was exerted within 24 h after irradiation. Suppression was dependent on the concentration of LPS added and LPS (2 micrograms/ml) derived from Salmonella minnesota R595 reduced the number of transformed type III foci per dish from 0.39 to 0.15. Indomethacin (1 to 30 microM) further enhanced the effect of LPS in a dose-dependent manner. PMID- 3089582 TI - Combination chemoprevention of rat mammary carcinogenesis by indomethacin and butylated hydroxytoluene. AB - Indomethacin, a nonsteroidal antiinflammatory agent which inhibits prostaglandin biosynthesis, is an effective inhibitor of mammary carcinogenesis in rats. However, the activity of indomethacin as a chemopreventive agent is limited by toxicity. The present studies were conducted to determine if the toxic and anticarcinogenic effects of indomethacin can be modified by the phenolic antioxidant, butylated hydroxytoluene (BHT). Simultaneous administration of BHT resulted in a dose-related inhibition of indomethacin toxicity in female Sprague Dawley rats, and increased the tolerable indomethacin dose from 50 to 150 mg/kg diet. When BHT (5000 mg/kg diet) and indomethacin (50 mg/kg diet) were administered in combination, no increased inhibition of 7,12 dimethylbenz(a)anthracene-induced mammary carcinogenesis was observed above that attained by administration of BHT alone or indomethacin alone at those doses. However, when the indomethacin dose was increased to 100 mg/kg diet, an enhanced inhibition of carcinogenesis was attained when BHT and indomethacin were administered from 2 weeks prior to until 1 week after 7,12 dimethylbenz(a)anthracene administration. These data indicate that "combination chemoprevention" regimens can be utilized to reduce the toxicity of anticarcinogenic drugs. However, the BHT-indomethacin interaction appears to involve a functional or dispositional antagonism which limits the anticarcinogenic efficacy of increasing indomethacin dose level. PMID- 3089581 TI - Serotherapy of primary rat mammary carcinoma: inhibition by ethylenedinitrilotetraacetic acid but not by [ethylenebis(oxyethylenenitrilo)]tetraacetic acid. AB - We reported inhibition of growth of primary rat mammary carcinomas after infusions of tumor-bearer plasma absorbed with Protein A-Sepharose or inactivated CNBr Sepharose. Absorbed plasmas were depleted of the third component of complement (C3) (other complement components defined similarly) and C5 but not C1, C4, or C2. These results suggested that activation of the alternative pathway of complement might be involved in the observed antitumor effects. To test this concept sera were treated with ethylenedinitrilotetraacetic acid or [ethylenebis(oxyethylenenitrilo)]tetraacetic acid before absorption with Protein A-Sepharose. Ethylenedinitrilotetraacetic acid, by chelating calcium and magnesium, prevents activation of both the alternative and classical complement pathways. [Ethylenebis(oxyethylenenitrilo)]tetraacetic acid, by chelating calcium but not magnesium, permits activation of the alternative pathway but inhibits activation of the classical complement pathway. Sera in the presence or absence of chelating agent were absorbed with Protein A-Sepharose twice at room temperature. After absorption calcium was added to the sera. Rats were treated by i.v. injection of sera twice a week for 2 weeks. Measurements of tumor size were made weekly for 5-7 weeks and then tumor weight was determined. Groups were compared both for size of index and total tumors. The results can be summarized as follows: tumor-bearer sera before absorption did not inhibit the growth of rat primary mammary carcinomas; tumor-bearer sera after absorption with Protein A Sepharose showed significant consumption of C3 and did inhibit tumor growth; tumor-bearer sera absorbed in the presence of ethylenedinitrilotetraacetic acid did not show a decrease in C3 functional activity and did not inhibit tumor growth; tumor-bearer sera absorbed in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid did show a decrease in C3 functional activity and did inhibit tumor growth; sera from normal adult female rats after absorption with Protein A-Sepharose did inhibit tumor growth. The results are consistent with a role for the alternative pathway of complement in the inhibition of growth of rat primary mammary carcinomas observed after treatment with absorbed sera. PMID- 3089583 TI - Cytotoxicity and DNA lesions produced by mitomycin C and porfiromycin in hypoxic and aerobic EMT6 and Chinese hamster ovary cells. AB - Solid neoplasms may contain deficient or poorly functional vascular beds, a property that leads to the formation of hypoxic tumor cells, which form a therapeutically resistant cell population within the tumor that is difficult to eradicate by ionizing irradiation and most existing chemotherapeutic agents. As an approach to the therapeutic attack of hypoxic cells, we have measured the cytotoxicity and DNA lesions produced by the bioreductive alkylating agents mitomycin C and porfiromycin, two structurally similar antibiotics, in oxygen deficient and aerobic cells. Mitomycin C and porfiromycin were preferentially cytotoxic to hypoxic EMT6 cells in culture, with porfiromycin producing a greater differential kill of hypoxic EMT6 cells relative to their oxygenated counterparts than did mitomycin C. Chinese hamster ovary cells were more resistant to these quinone antibiotics; although in this cell line, porfiromycin was significantly more cytotoxic to hypoxic cells than to aerobic cells, and the degree of oxygenation did not affect the toxicity of mitomycin C. Alkaline elution methodology was utilized to study the formation of DNA single-strand breaks and DNA interstrand cross-links produced by mitomycin C and porfiromycin in both EMT6 and Chinese hamster ovary cells. A negligible quantity of DNA single-strand breaks and DNA interstrand cross-links were produced in hypoxic and aerobic Chinese hamster ovary cells by exposure to mitomycin C or porfiromycin, a finding consistent with the considerably lower sensitivity of this cell line to these agents. In EMT6 tumor cells, no single-strand breaks appeared to be produced by these antitumor antibiotics under both hypoxic and aerobic conditions; however, a significant number of DNA interstrand cross-links were formed in this cell line following drug treatment, with substantially more DNA interstrand cross-linking being produced under hypoxic conditions. Mitomycin C and porfiromycin caused the same amount of cross-linking under conditions of oxygen deficiency; however, mitomycin C produced considerably more DNA cross-linking than did porfiromycin in oxygenated cells. DNA interstrand cross-links were observed in hypoxic EMT6 cells throughout a 24-h period following removal of mitomycin C and porfiromycin, with a decrease in DNA interstrand cross-links observed at 24 h. An increase in DNA interstrand cross-links occurred in aerobic EMT6 cells treated with mitomycin C and porfiromycin at 6 h after drug removal, with a decrease in these lesions being observed by 24 h, suggesting that the rate of formation of the cross-links may be slower and the removal of cross-links more rapid under aerobic conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3089584 TI - Genetic control of resistance to chemically induced mammary adenocarcinogenesis in the rat. AB - Fifty-day-old female rats of a series of outbred (i.e., SD) and inbred (i.e., NSD, WF, LEW, F344, ACI, and COP) strains were exposed to a single dose of either of two highly effective mammary chemical carcinogens, 7,12 dimethylbenz[a]anthracene (DMBA) or 1-methyl-1-nitrosourea (MNU), to determine the characteristic number of mammary adenocarcinomas induced/rat for each strain. Female rats of the inbred NSD, WF, and LEW strains were found to be as highly susceptible to DMBA exposure as the randomly outbred SD strain (i.e., greater than 2 mammary adenocarcinomas/rat develop). Inbred female F344 and ACI rats were found to be much less susceptible to DMBA induced mammary adenocarcinogenesis (i.e., less than 1.2 mammary adenocarcinomas/rat). In contrast to all the other inbred strains, the female COP rat was unique in that it is essentially completely resistant to all attempts to induce mammary adenocarcinomas by either DMBA or MNU exposure. Genetic breeding analysis demonstrated that the resistance of the mammary epithelium of the female COP rat to DMBA and MNU is due to the mendelian inheritance of a dominant, autosomal genetic allele. The inheritance of a single copy of this resistance allele is able to prevent both the DMBA and MNU induced development of mammary adenocarcinomas in F1 hybrids produced by cross breeding COP to the highly susceptible NSD animal. PMID- 3089585 TI - Mitomycin-induced chromatid breaks in HeLa cells: a consequence of incomplete DNA replication. AB - The formation of chromosome aberrations induced by alkylating agents such as mitomycin C has been shown to require the passage of the treated cell through S phase. However, the exact mechanisms by which mitomycin C-induced DNA lesions are translated into chromosome aberrations during S phase are not known. The purpose of these studies was to better understand the molecular basis of chromosome aberration formation after mitomycin C treatment. The morphology of metaphases of cells treated in G1 phase with mitomycin C resembled that of prematurely condensed chromosomes of S-phase cells. Consequently we postulated that chromosome aberrations resulted from cells reaching mitosis without completing DNA replication. This was tested by treating HeLa cells in G1 phase with mitomycin C and then analyzing these cells at mitosis for residual DNA damage and DNA content. Utilizing the DNA alkaline elution assay for DNA damage, we showed that HeLa cells progress through S phase into mitosis with intact DNA-DNA interstrand cross-links. These cross-links, originally induced into parental DNA, were associated equally with parental and newly replicated DNA at the time the cells reached mitosis. This suggests that recombinational events had taken place during the DNA replication process. Cells that were treated in G1 phase and allowed to proceed to mitosis in the presence of bromodeoxyuridine to density label newly replicated DNA were analyzed with cesium chloride density sedimentation. Unreplicated DNA was present in the mitotic cells of the treated populations but not in the untreated control cells. Further, flow cytometric measurements, made under hypotonic conditions in order to reduce chromatin condensation effects, demonstrated that the mitotic cells from the mitomycin C treated populations contained 10-20% less DNA than untreated mitotic controls. These results indicate that chromosome breaks induced by mitomycin C are the result of cells reaching mitosis without having fully completed DNA replication. PMID- 3089586 TI - Metabolism of aflatoxin B1 in the upper airways of the rabbit: role of the nonciliated tracheal epithelial cell. AB - Short-term tracheal explant cultures from the rabbit were used to study the metabolism of the carcinogen aflatoxin B1 (AFB1) and to determine the cell types that are susceptible to damage by AFB1 and their relative contents of monooxygenase enzymes. Tracheas were cultured in serum-free medium for 0.5-24 h with 0.7 microM [3H]AFB1, and metabolism was measured by determining the level of binding of the carcinogen to DNA and by the release of metabolites into the medium. The binding of aflatoxin B1 was time dependent and appeared to peak at 12 h in culture. In addition, the metabolites aflatoxicol, aflatoxin M1, and aflatoxin Q1 were produced by the explants. Ultrastructural evaluation of cultured tracheas showed degenerative changes exclusively in nonciliated secretory cells after 4 h in culture. Extensive nonciliated secretory cell necrosis was evident by 12 h. Ciliated cells did not show degenerative changes until 12 h and appeared much more viable after 24-h exposure to AFB1 relative to the nonciliated cells. Tracheal sections stained to demonstrate rabbit lung cytochrome P-450, Forms 2 and 5, and cytochrome P-450 reduced nicotinamide adenine dinucleotide phosphate reductase by an immunoperoxidase technique showed intense staining selectively within nonciliated cells. In total, the data revealed that: (a) rabbit tracheal explants are able to metabolize aflatoxin B1; (b) the nonciliated secretory cell population in this tissue is the target cell for cytotoxicity of this carcinogen; and (c) as is the case in the more distal airways, the nonciliated epithelial cells appear to have a high content of components of the pulmonary cytochrome P-450 monooxygenase system, which may be an important factor in the susceptibility of these cells and this region of the airways to suspected airborne carcinogens. PMID- 3089588 TI - Anticancer effects of local administration of mitomycin C via the hepatic artery or portal vein on implantation and growth of VX2 cancer injected into rabbit liver. AB - Rabbits were inoculated with a suspension of VX2 carcinoma cells in the liver, and mitomycin C was given via the hepatic artery or the portal vein for a study of the anticancer effects. Twenty-eight rabbits were killed for preliminary study at 1 h or 1, 3, 7, 9, 12, or 14 days after the inoculation. Another 36 rabbits were divided into three groups. Groups A and B were given the agent (0.5 mg/kg), 1 h after the inoculation and on Days 2, 4, 6, and 8, into the common hepatic artery or the splenic vein, respectively. Group C was not treated after inoculation. The mean numbers of cancer nodules per rabbit in Groups A, B, and C were 11.9, 36.4, and 83.4, respectively, at 12 days after inoculation. The number of cancer nodules of Group A was smallest (P less than 0.025, F test). The means of the total cross-sectional area of tumor nodules in Groups A, B, and C were 32.7, 79.7, and 217.3 mm2, respectively. The total cross-sectional area of the cancer nodules of Group A was smallest (P less than 0.05, F test). These results suggest that the anticancer agents given via the hepatic artery had better effects on early (small) metastatic liver tumor than those via the portal vein. PMID- 3089587 TI - Selective inhibition of proteolytic enzymes in an in vivo mouse model for experimental metastasis. AB - Peptide aldehyde transition state analogue inhibitors of serine and cysteine proteases have been used to selectively inhibit proteases for which prior evidence supports a role in tumor cell metastasis. These enzymes include cathepsin B, urokinase plasminogen activator (PA), and thrombin. The inhibition constants of the peptidyl aldehyde inhibitors show that they are highly selective for a particular targeted serine or cysteine protease. The inhibitors are introduced by i.p. injection or by miniosmotic pumps into syngeneic C57BL/6 mice also given injections of B16-F10 melanoma cells, and the number of metastatic foci in the lung was determined. While the injection protocol gave an initially high but changing in vivo concentration of inhibitor over time, the minipump implant gave a constant steady state concentration of inhibitor over 5-7 days. Minipump infusion of leupeptin (acetylleucylleucylargininal), a strong inhibitor of cathepsin B at a steady state plasma concentration 1000-fold greater than its Ki(cathepsin B), gave no significant decrease in lung colonization by the B16 tumor cells. Ep475, a stoichiometric irreversible peptide inhibitor of cathepsin B-like proteases, also did not significantly inhibit metastatic foci formation. Introduction of selective inhibitors of urokinase PA, tert butyloxycarbonylglutamylglycyl-argininal and H-glutamylglycylargininal at concentrations near its Ki, produced no significant decrease in mouse lung colonization. The selective thrombin inhibitor D-phenylalanylprolylargininal infused to a steady state concentration 100-fold greater than its Ki dramatically increased B16 melanoma colonization of mouse lung. The results indicate that neither secreted cathepsin B-like nor urokinase PA have roles in B16 colonization of mouse lung, while thrombin may have a role in preventing metastasis. These experiments do not eliminate roles for a cathepsin B-like enzyme or urokinase PA in the initial steps of the metastatic process. PMID- 3089590 TI - Effects of recombinant human tumor necrosis factor alpha, recombinant human gamma interferon, and prostaglandin E on colony formation of human hematopoietic progenitor cells stimulated by natural human pluripotent colony-stimulating factor, pluripoietin alpha, and recombinant erythropoietin in serum-free cultures. AB - The influences of pure human pluripotent colony-stimulating factor, highly purified pluripoietin alpha, pure recombinant human tumor necrosis factor alpha, pure recombinant human gamma-interferon, and natural prostaglandin E1 (PGE1) were evaluated on colony formation of multipotential and erythroid progenitor cells in the presence of recombinant erythropoietin and hemin and on colony formation of granulocyte-macrophage progenitors in normal human marrow cultured in the presence or absence of serum. Serum was replaced by bovine serum albumin, iron saturated transferrin, cholesterol, and calcium chloride. Increasing concentrations of pluripotent colony-stimulating factor and pluripoietin alpha stimulated increasing numbers of colonies from nonadherent low-density T lymphocyte-depleted cells in the absence and presence of serum. Growth was usually greater in the presence of serum and on a unit basis pluripoietin alpha was more active than pluripotent colony-stimulating factor. Recombinant human tumor necrosis factor alpha and recombinant human gamma-interferon suppressed colony formation colony forming unit-granulocyte-macrophage, burst forming unit erythroid, and colony forming unit-granulocyte-erythroid-macrophage megakaryocyte; PGE1 suppressed colony formation by colony-forming unit granulocyte-macrophage, stimulated colony formation by burst forming unit erythroid, and had no effects on colony formation by colony forming unit granulocyte-erythroid-macrophage-megakaryocyte in both serum-containing and serum free medium. The PGE1 enhancing effects on erythroid colony formation required T lymphocytes. Thus, results are similar using serum-containing and serum-free cultures of human bone marrow cells and serum-free defined culture medium can be used to study the mechanism of action of purified natural and recombinant growth and suppressor molecules in vitro. PMID- 3089591 TI - Kinetics of formation and disappearance of 7,12-dimethylbenz(a)anthracene:DNA adducts in mouse epidermis. AB - The rates of formation and disappearance of 7,12-dimethylbenz(a)anthracene (DMBA):DNA adducts were analyzed in the epidermis of SENCAR mice over a 21-day time course. Mice were treated topically with 10 nmol of tritium-labeled DMBA per mouse at various times prior to sacrifice. Under these experimental conditions, total covalent binding of DMBA to epidermal DNA reached a peak at 24 h, and thereafter, DMBA:DNA adduct disappearance was biphasic. The early phase of DMBA:DNA adduct disappearance (Phase A) between 24 and 72 h had a half-life of 3.17 +/- 1.1 days, whereas the later phase (Phase B) had a half-life of 6.46 +/- 1.3 days. A comparison of the biphasic disappearance of total DMBA:DNA adducts with total benzo(a)pyrene:DNA adducts at comparable tumor-initiating doses (i.e., doses producing similar papilloma responses in SENCAR mice) revealed that the half-life for Phase A disappearance of benzo(a)pyrene:DNA adducts was approximately 3 times faster than for DMBA:DNA adducts (1.08 +/- 0.3 days versus 3.17 +/- 1.1 days), respectively. Phase B disappearance of DNA adducts was essentially identical for both hydrocarbons and was similar to the rate of loss of label in epidermal DNA due to cell turnover. The rates of formation and disappearance of the three major DNA adducts derived from DMBA were also examined. Peaks II (syn-diol-epoxide deoxyadenosine) and III (anti-diol-epoxide deoxyadenosine) disappeared more rapidly than Peak I (anti-diol-epoxide deoxyguanosine) beyond 24 h. The data support the conclusion that, for a particular hydrocarbon such as DMBA, deoxyadenosine adducts disappear from epidermal DNA faster than the corresponding deoxyguanosine adducts. In addition, the data suggest that, at the doses used, total DMBA:DNA adducts disappear initially more slowly from epidermal DNA than benzo(a)pyrene:DNA adducts. PMID- 3089589 TI - Correlation between formation of a specific hydrocarbon-deoxyribonucleoside adduct and tumor-initiating activity of 7,12-dimethylbenz(a)anthracene and its 9- and 10-monofluoroderivatives in mice. AB - The formation of epidermal DNA adducts from 9-fluoro-7,12 dimethylbenz(a)anthracene (9-F-DMBA) was compared with 7,12 dimethylbenz(a)anthracene (DMBA) and 10-fluoro-7,12-dimethylbenz(a)anthracene (10 F-DMBA) in SENCAR mice. 9-F-DMBA is equipotent, whereas 10-F-DMBA is more potent than DMBA for skin tumor initiation in this mouse stock. The quantity of covalently bound DNA adducts was essentially identical between 9-F-DMBA and DMBA at all doses tested in the range of 10 to 100 nmol/mouse. These results correlated closely with the dose-response relationships for tumor initiation by the two hydrocarbons. A quantitative comparison of the hydrocarbon-DNA adducts formed after topical application of 100 nmol of DMBA, 9-F-DMBA, and 10-F-DMBA yielded interesting results. The total binding for the three hydrocarbons at this dose was 16.2 +/- 2.6, 18.4 +/- 2.4, and 52.3 +/- 6.8 pmol/mg of epidermal DNA, respectively. Analysis of these DNA adduct samples by dihydroboronate chromatography demonstrated marked reductions in the percentage of syn-diol epoxide-DNA adducts with both 9-F-DMBA (24%) and 10-F-DMBA (18%) compared with DMBA (57%). Analysis of DNA adduct samples from DMBA-, 9-F-DMBA-, and 10-F-DMBA treated mice (100 nmol/mouse) by high-pressure liquid chromatography revealed qualitatively similar profiles. However, a quantitative comparison of the three major DNA adducts, tentatively identified as anti-diol-epoxide-deoxyguanosine (Peak I), syn-diol-epoxide-deoxyadenosine (Peak II), and anti-diol-epoxide deoxyadenosine (Peak III), revealed significant differences. With both 9-F-DMBA and 10-F-DMBA there were marked increases (236% and 644%, respectively) in the quantity of Peak I compared to DMBA. On the other hand, Peak II was formed in approximately equal amounts with DMBA and 10-F-DMBA but only 50% of the DMBA value with 9-F-DMBA. Interestingly, Peak III was formed in approximately equal amounts with both DMBA and 9-F-DMBA but was increased to 337% of the DMBA value with 10-F-DMBA. Thus, the actual level of Peak III (tentatively identified as anti-diol-epoxide-deoxyadenosine) correlated closely with the tumor-initiating activity of these three hydrocarbons, whereas the levels of the other two adducts did not. These data suggest that formation of a specific DNA adduct may be important for DMBA skin tumor initiation. These data are discussed in relation to skin tumor initiation by other hydrocarbons. PMID- 3089593 TI - Differential effects of transforming growth factor-beta on proliferation of normal and malignant rat liver epithelial cells in culture. AB - Transforming growth factors (TGF-betas) have been shown to cause both stimulatory and inhibitory effects on cellular growth in a variety of normal and neoplastic cells. The nature of the inhibitory effects of TGF-beta on proliferation of different cell types is at present unclear. We have used freshly isolated rat hepatocytes, a normal diploid rat liver epithelial cell line (NRLM), and a subline (AFB) derived from it which was transformed in vitro by aflatoxin B1 to study the nature of TGF-beta-induced growth inhibition and its alteration following chemically induced neoplastic transformation. TGF-beta had a vastly different effect on proliferation of normal rat liver epithelial cells (both freshly isolated and NRLM cells) compared to aflatoxin B1-transformed cells. TGF beta at 20 pg/ml caused 83% inhibition of colony formation of NRLM, whereas the growth of AFB cells was unaffected by TGF-beta at concentrations as high as 10 ng/ml. A parallel dose-dependent inhibition of DNA synthesis by TGF-beta was observed in both primary hepatocytes and NRLM cells at concentrations between 10 pg and 10 ng/ml. No inhibition of DNA synthesis was observed in AFB cells. Furthermore, TGF-beta did neither induce anchorage-independent growth of NRLM cells nor affect the growth of AFB cells in soft agar. TGF-beta-induced inhibition of the NRLM cells was irreversible in nature, since treated cells were unable to proliferate and form colonies upon removal of TGF-beta from the medium. Also, NRLM cells showed, after 4 days in the presence of 20 pg of TGF-beta per ml morphological changes characterized by cytoplasmic hypertrophy and the formation of abundant liposomal derivatives, some of which resemble lipofuscin. The finding that TGF-beta caused a high degree of irreversible inhibition of NRLM cells emphasizes the need for caution in interpreting data from inhibition studies, since most assays presently used are designed for assessing growth stimulation in vitro and do not adequately distinguish between the possible cytotoxic and/or cytostatic action of growth inhibitors. PMID- 3089592 TI - Adoptive cellular immunotherapy of human ovarian carcinoma xenografts in nude mice. AB - Adoptive cell therapy with various purified populations of human lymphoid and monocytoid effector cells which have been in vitro activated with recombinant interleukin 2 and gamma-interferon was performed in an in vivo nude mouse model of human ovarian cancer. Administration i.p. of human interleukin 2-activated populations of large granular lymphocytes resulted in a significant extension of mean survival time (30 to 60 days) in this ovarian carcinoma model. In addition, T-cells activated with interleukin 2, in a similar fashion to large granular lymphocytes, also significantly prolonged survival of animals with ovarian carcinoma. In contrast, monocytes, with or without gamma-interferon activation, did not improve survival of tumor-bearing mice. In vitro results using direct isotopic release assays to measure efficacy of effectors against the ovarian cancer cells before and after activation, especially the activated natural killer cells, paralleled the effects on survival in the nude mouse model. However, the results with T-cells were somewhat inconsistent in vitro regarding their in vivo efficacy. We assume this is due to a delayed generation of activated killing in T cells that is generated in vivo. These experimental results in this model system of human ovarian cancer indicate that transfer of autologous activated cells may have a role in the treatment of ovarian cancer patients. PMID- 3089594 TI - Induction of malignant transformation of cocultivated hematopoietic stem cells by X-irradiation of murine bone marrow stromal cells in vitro. AB - X-irradiation of purified primary cultures of mouse bone marrow stroma or permanent cloned marrow stromal cell lines in plateau phase decreases production of macrophage progenitor cell-specific colony-stimulating factor to a plateau minimum of 40% of control levels after doses of 50 to 500 Gy delivered at 2 Gy/min. After 50 Gy there is increased bioavailability of another growth factor(s) that is distinct from macrophage progenitor cell-specific colony stimulating factor, granulocyte-macrophage progenitor cell colony-stimulating factor, or colony-stimulating factor for multipotential hematopoietic stem cells (interleukin 3). Liquid-phase cocultivation of irradiated stromal cells with either nonadherent cells from continuous marrow cultures or cloned dual granulocyte-macrophage progenitor cell colony-stimulating factor/interleukin 3 dependent hematopoietic progenitor cell lines induces evolution over 5 weeks of factor-independent colony-forming cells. Subcultured factor-independent colonies generated clonal malignant cell lines with multiple distinct karyotypic alterations. Inoculation of 10(6) cells s.c. from factor-independent clones into syngeneic mice produces local granulocytic monomyeloid tumors with spread to spleen, lymph nodes, and bone marrow. These data provide the first demonstration in vitro of indirect X-irradiation leukemogenesis through cells of the marrow stroma. PMID- 3089596 TI - Phase II study of ifosfamide in cervical cancer. AB - Thirty patients with symptomatic, progressive squamous cell carcinoma of the uterine cervix no longer amenable to surgery or radiotherapy were entered in a phase II study of ifosfamide (IFX). Patients were treated with IFX (5 g/m2 iv given over 24 hours) and concomitant mesna (total dose, 9.2 g/m2 iv given over 36 hours) every 21 days. One complete response (duration, 10+ months) and nine partial responses were observed, with an overall median response duration of 6.5 months. The median survival of responding patients was 11 months. Objective response rates for lesions arising in previously irradiated sites (four of 22) were significantly lower than for lesions arising in nonirradiated sites (15 of 28) (P = 0.018). There were two treatment-related deaths: one due to leukopenia associated infection in a patient with peritonitis and severe central nervous system toxicity and one due to central nervous system toxicity without complicating factors. One other patient developed severe but reversible encephalopathy. In all remaining patients hemorrhagic cystitis and hematological and gastrointestinal toxic effects were predictable and manageable. Treatment was delayed for 1 week due to toxicity on seven of 101 occasions: four of these delays were due to mild, reversible impairment of renal function and three were due to leukopenia. Complete though reversible alopecia occurred in 22 of 30 patients. The results indicate that IFX is active in cervical cancer and deserves further study in this setting. PMID- 3089595 TI - Phase I study of ICRF-187 in pediatric cancer patients and comparison of its pharmacokinetics in children and adults. AB - A phase I study of ICRF-187 as a 2-hour iv infusion daily for 3 days was conducted in 46 evaluable pediatric patients. The maximum tolerated dose was 3500 mg/m2/day X 3 based on changes in hepatic function and coagulation abnormalities encountered when larger dosages were administered. One patient with acute lymphocytic leukemia achieved a complete remission and four cleared the blood of lymphoblasts. No other objective responses were seen. Pharmacokinetic analysis showed that the children had a larger volume of distribution per kilogram of body weight in the central compartment and total body and a more rapid total-body clearance than adults. These parameters can explain only part of the increased tolerance of children to ICRF-187. PMID- 3089597 TI - Role of hexamethylmelamine in the treatment of ovarian cancer: where is the needle in the haystack? AB - Hexamethylmelamine (HMM) was selected for development as an antineoplastic agent because it demonstrated activity in a variety of preclinical tumor models. Its mechanism of action is unknown. It has been used in clinical trials since 1964. The clinical toxic effects have consisted of signs and symptoms involving the following systems: gastrointestinal (nausea, vomiting, anorexia), hematologic (leukopenia, mild anemia), and neurologic (critical depression, hallucinations, peripheral motor and sensory deficits). Antitumor activity against advanced ovarian cancer was demonstrated in phase I trials and the drug was quickly incorporated into trials which utilized drug combinations. The majority of these have consisted of phase II trials without an identified control population. As might be predicted, all of the HMM-containing combinations are active. However, the contribution of HMM to the antitumor activity of the combination remains conjectural. Thus, in spite of greater than 15 years of clinical trials with a drug that has single-agent activity, the questions regarding the role of HMM in the treatment of ovarian cancer remain unanswered. PMID- 3089598 TI - The surgical management of intracranial hematomas in hemophiliac children. A prospective study. AB - A prospective study was undertaken to treat all intracranial hematomas in hemophiliac A children under a uniform protocol. Patient selection was obtained by early CT scan of all hemophiliacs presenting with neurological symptoms and routine hematological screening for coagulopathies of all pediatric intracranial hematomas, spontaneous or traumatic. Nine patients, of whom seven came under category 1 and two under category 2, were entered into this study. There were eight subdural hematomas, one epidural hematoma, and one intracerebral hematoma. Surgery was required in every patient. Human factor VIII concentrate was used for replacement up to 100% just before and 3 days after surgery. Thereafter, it was maintained at 50% up to the 10th postoperative day. There was no operative or late mortality. At 6-month follow-up, eight of nine patients had recovered completely with no residual neurological deficit. We conclude that early diagnosis, prompt surgical intervention, and perfect normalization of hemostatic defect are essential in improving the outcome of these patients. PMID- 3089599 TI - Electroencephalography in minor head injury in children. AB - EEG and CT scans of 280 cases of minor head injury in children under 15 years of age were studied. Abnormality on initial EEG was shown in 42.5%. Those who lost consciousness had a higher incidence of abnormality than those who did not, and it was higher between 4 and 13 years of age. The sleep state has much influence on the finding. The patients should be awake or in a light sleep stage. The most frequent abnormality was slow waves, seen predominantly in the occipital regions, and which tended to disappear more easily than the paroxysmal ones. The EEGs became or remained normal in 95%, excluding incompletely followed-up cases. There was no case of post-traumatic epilepsy in our series, but 4 cases of post traumatic early convulsions, in which the EEGs were variable. CT scan disclosed abnormality in 6%. PMID- 3089601 TI - UDP-N-acetyl-D-galactosamine as a donor substrate for the glycosyltransferase encoded by the B gene at the human blood group ABO locus. AB - The properties of the enzyme in the serum of blood group B individuals that catalyses the transfer of small amounts of N-acetyl-D-galactosamine to H-active precursor structures were compared with those of the blood group B gene associated alpha-(1----3)-D-galactosyltransferase and with the blood group A gene associated alpha-(1----3)-N-acetyl-D-galactosaminyltransferases in the serum of blood group A1 and A2 individuals. The biosynthetic products formed by the enzyme in B serum were identical with the A-active structures synthesised by the A1 and A2 gene-associated alpha-(1----3)-N-acetyl-D-galactosaminyltransferases but the enzyme differed from the A1 and A2 transferases in its apparent Km for UDP-N acetyl-D-galactosamine, its heat susceptibility, its failure to bind to Sepharose 4B, and its adsorption to H-active sites on group O red cell ghosts under conditions which bind the B transferase but fail to adsorb the A1 and A2 transferases. The correlation between the levels of alpha-(1----3)-D galactosyltransferase and alpha-(1----3)-N-acetyl-D-galactosaminyltransferase activities in all the group B serum samples tested, the maintenance of the same ratio of activities after successive cycles of binding to group O red cell ghosts, the retention of the ability to convert blood group O to A-active cells after treatment of the serum with Sepharose 4B, and the failure to detect any comparable activity in group O serum samples tested under the same conditions indicated that the enzyme in group B serum that utilises UDP-N-acetyl-D galactosamine to make blood group A-active structures is the B gene-associated alpha-(1----3)-D-galactosyltransferase. PMID- 3089600 TI - Biosynthesis in vitro of a globoside containing a 2-acetamido-2-deoxy-beta-D galactopyranosyl group (1----3)-linked and Forssman glycolipid by two N acetylgalactosaminyltransferases from chemically transformed guinea pig cells. AB - Two N-acetylgalactosaminyltransferase activities (GalNAcT-2 and GalNAcT-3) have been characterized in chemically transformed, cultured guinea-pig cell lines (104C1 and 106B). Line 104C1 is a benz[a]pyrene-transformed tumorigenic variant, whereas line 106B is a 7,12-dimethylbenz[a]anthracene-transformed nontumorigenic variant obtained from fetal guinea-pig cells at 43 days of gestation. The GalNAcT 2 (UDP-GalNAc:GbOse3Cer beta-N-acetylgalactosaminyltransferase) isolated from both 104C1 and 106B cells catalyzed the transfer of Gal-NAc from UDP-GalNAc to the 3H-labeled terminal galactose group of Gb3 [( 6-3H]Gal alpha 1----4Gal beta 1 ---4Glc----Cer). The 3H-labeled globoside was purified and then subjected to exhaustive methylation. After acetolysis, the partially methylated sugars were separated by two-dimensional, thin-layer chromatography. 3H-Label was detected in two major areas, 2,4,6-tri-O-Me-Gal (40%) and 2,3,4,6-tetra-O-Me-Gal (46%). In a separate experiment, 80% of the GalNAc was released when labeled GbOse4Cer [( 3H]GalNAc----Gal alpha 1----4Gal beta 1----4Glc----Cer) was treated with purified clam beta-hexosaminidase. The present results establish the formation of a beta-D GalpNAc-(1----3) linkage in the terminal region of the biosynthesized globoside. GalNAcT-3 activity (UDP-GalNAc:GbOse4Cer alpha-GalNAc-transferase), which catalyzes the transfer of GalNAc from UDP-[14C]- or -[3H]GalNAc to GbOse4Cer (GalNAc beta 1----3Gal alpha 1----4Gal beta 1----4Glc----Cer), was three times higher in 106B cells than in 104C1 cells. The isolated, purified radioactive product formed an immunoprecipitin line against rabbit anti-Forssman antibody. PMID- 3089603 TI - The modulation of bovine milk D-galactosyltransferase by various phosphatidylethanolamines. AB - To investigate the possible role of nonbilayer phases in the modulation of glycosyltransferase activity, bovine milk D-galactosyltransferase has been studied in phosphatidylethanolamine (PE) membranes, including soybean PE, egg PE, PE prepared by transphosphatidylation of egg PC, bovine brain PE, plasmalogen PE, and DPPE. The gel-to-liquid crystalline transition (TC) and the lamellar-to hexagonal transitions (TH) are known for most of the PE compounds. The lower the TC (or TH) value, the greater the stimulation of galactosyltransferase activity in both the lactose- and N-acetyllactosamine-synthetase reactions. No correlation was found between either TC or TH value and the break in the Arrhenius plots for the N-acetyllactosamine synthetase. In membranes consisting of mixtures of PE with PC, the dominant effect was that of PC. The stimulation of activity in the mixed-lipid systems was never greater than that produced by PC alone, therefore the enzyme showed a definite preference for PC in the mixtures. PMID- 3089602 TI - Monoclonal antibodies to soluble, human milk galactosyltransferase (lactose synthase A protein). AB - Monoclonal antibodies have been produced against soluble human milk galactosyltransferase of a blood group O donor. After initial screening by radioimmunoassay, fourteen hybridomas were further characterized by enzyme-linked immunosorbent assay, immunoblotting of purified enzyme following sodium dodecyl sulfate-polyacrylamide gel electrophoresis, enzyme activity modification, and enzyme localization in HeLa cells by immunofluorescence. Of these fourteen clones, seven had titers between 1500 and 7800 as estimated by ELISA. In general, the titer correlated with staining intensity on immunoblots and in immunofluorescence. In the presence of monoclonal antibody, enzyme activity was usually slightly enhanced or stabilized. Subcloning yielded four monoclonal antibody preparations designated as GT2/24/108, GT2/36/118, GT2/61/14, and GT2/77/22, which belong to Ig class G2b, G3, M, and G1, respectively. They all recognized the enzyme in purified form or in defatted milk as a single, broad band on electrophoresis-immunoblotting and produced a concise juxtanuclear fluorescence typical for the Golgi apparatus in HeLa cells. PMID- 3089604 TI - Reconstitution of the masking effect of sialic acid groups on sialidase-treated erythrocytes by the action of sialyltransferases. AB - Glutardialdehyde-fixed or native rat erythrocytes were partially desialylated by the action of Vibrio cholerae sialidase, resulting in the binding of these cells to homologous peritoneal macrophages. Resialylation of these erythrocytes by purified alpha-(2----3)- or alpha-(2----6)-sialyltransferases with CMP-N acetylneuraminic acid led to the incorporation of 60-80% of the enzymically released sialic acid. Binding of the resialylated erythrocytes to peritoneal macrophages was reduced when compared with corresponding, partially desialylated erythrocytes. Thus, the amount of transferred sialic acid was sufficient to demonstrate reconstitution of the masking effect of sialic acids. PMID- 3089605 TI - The effect of experimental carcinogenesis on intestinal diamine oxidase, a polyamine deaminating enzyme. AB - Intestinal mucosa hyperproliferation is an important risk factor of large bowel carcinoma development. Intestinal diamine oxidase (DAO) is suggested to be a proliferation terminating principle in the mature mucosa. Therefore, the influence of the carcinogen azoxymethane (AOM) on this enzyme was studied. The enzyme was measured with the 14C-putrescine assay. In vitro the enzyme was inhibited only by excessive high concentrations of AOM (89 mmol/liter). In vivo the enzymic activity was reduced in the duodenum but not in the colon during the first 48 hr after AOM application (15 mg/kg). Ten weekly injections of AOM reduced the DAO activity in the duodenum and colon significantly (alpha = 0.05). After the stop of the AOM application a significant (alpha = 0.05) increase of DAO activity over the control level was found which was interpreted as a defense reaction of the mucosa against the hyperproliferation that had occurred during the carcinogen treatment. Intestinal DAO is regarded as an antiproliferative principle protecting the integrity of the intestinal mucosa. An inhibition of this enzyme probably increases the risk of intestinal carcinoma promotion. PMID- 3089606 TI - Entrapment of below-the-knee bypass grafts. AB - A case is presented in which a below-the-knee saphenous vein bypass graft was compressed between the sartorius and the semimembranosis, semitendinosis, and gracilis muscles. Angiography and noninvasive Doppler showed occlusion with leg extension but no obstruction to flow with flexion. Recognition of this entrapment syndrome and its prompt correction can preserve patency of the graft. PMID- 3089607 TI - Leiomyosarcoma of the superior vena cava: diagnosis by cardiac gated MR. AB - A primary leiomyosarcoma of the superior vena cava was diagnosed with magnetic resonance imaging. MRI demonstrated tumor extension into the right heart and innominate veins and compared favorably with the superior vena cavagram. PMID- 3089608 TI - Upper-extremity venography using digital subtraction angiography. AB - Venography to evaluate the patency of upper-extremity veins was performed with digital subtraction angiography (DSA) and conventional angiography. Venous thrombosis was easily diagnosed, and the innominate veins and superior vena cava were more easily visualized using DSA. Iodine concentration for DSA was one-third that of conventional venography, and the examination time was reduced by 50% using DSA. Patient comfort and acceptance were greater with DSA. DSA is a superior technique for upper-extremity vein evaluation in cooperative patients. PMID- 3089610 TI - Double-coated medical tape modification of finger trap method for anchoring drainage catheters to the skin. AB - The authors describe a simple method using double-coated medical tape to improve adherence between a finger trap suture and a drainage catheter. They have used it on multiple types of catheters without failure. PMID- 3089609 TI - The optical push device: an aid to the angiographer. AB - The frequent use of heavy eyeglasses by the angiographer has resulted in significant discomfort due to "sliding glasses." Described is the optical push device, which allows the angiographer to adjust eyeglasses comfortably while maintaining sterility. PMID- 3089611 TI - Transcatheter embolization of uterine arteriovenous malformations. AB - A case of congenital arteriovenous malformation of the uterus in a 25-year-old woman with a long-standing history of recurrent menometrorrhagia is reported. Radiological diagnosis was based on hysterographic, computed tomographic, and angiographic findings. Treatment was performed with percutaneous transcatheter embolization. PMID- 3089612 TI - Percutaneous needle biopsy of deep pelvic masses: a posterior approach. AB - The classical approach for the fine-needle aspiration biopsy of deep pelvic masses has been through the lower anterior abdominal wall. With this approach, and using either CT or sonographic guidance, bowel or bladder may be unavoidably traversed to reach the mass. We have been using a posterior approach through the sciatic notch, which is a safe and simple procedure, with good results. The biopsy is done with the patient in a prone position, using a 22-gauge biopsy needle. With this technique we have successfully biopsied various neoplastic pelvic entities. PMID- 3089613 TI - Embolic management of rare hemorrhagic gynecologic and obstetrical conditions. AB - Severe life-threatening hemorrhage was controlled by angiographic management in 3 patients with bleeding due to unusual gynecological abnormalities and in 1 patient with a rare obstetrically related hemorrhage. Successful management of such rare causes of bleeding emphasizes that early angiographic intervention can, in selected patients, reduce the need for an immediate or subsequent surgical procedure and allow conservative management followed by disease-specific therapy. PMID- 3089615 TI - Subclavian aneurysm producing the subclavian steal syndrome. AB - An atherosclerotic aneurysm of the right subclavian artery causing subclavian steal syndrome is described. Complementary information obtained from digital subtraction angiography and computed tomography helped to establish a correct preoperative diagnosis. PMID- 3089614 TI - Selective low-dose streptokinase infusion in the treatment of acute transplant renal vein thrombosis. AB - A renal transplant recipient developed acute renal transplant vein thrombosis following surgery for a total hip replacement. As an alternative to standard surgical therapy, the patient was treated with selective intravenous low-dose infusion of streptokinase at doses of 5,000-20,000 units/h. The infusion was continued for 120 h with constant monitoring of PT, PTT, and fibrinogen levels. Therapy resulted in excellent preservation of renal function without complications. Low-dose selective infusion of streptokinase should be considered a potential alternative therapy for acute transplant renal vein thrombosis. PMID- 3089616 TI - Popliteal artery entrapment: importance of the stress runoff for diagnosis. AB - We review our experience with seven patients, (12 affected extremities) with popliteal artery entrapment. The classic angiographic finding of medial deviation of the popliteal artery was found in only three patients (four extremities). Four patients (eight extremities) had no medial deviation of their popliteal arteries and required a stress runoff examination to demonstrate arterial entrapment. Five patients had bilateral entrapment. This patient series underscores the need to consider possible arterial entrapment even when the popliteal arteries appear normal on the resting runoff examination as well as the importance of imaging both extremities since the incidence of bilateral entrapment may be higher than previously recognized. PMID- 3089617 TI - Extrarenal arterial connections of the normal renal artery. AB - An angiographic study in cadavers has demonstrated connections between the renal artery and remote vessels including the intercostal, testicular, and inferior mesenteric arteries in subjects with no known history of renal disease. Such communications are a potential route by which embolic material introduced into the renal artery may inadvertently reach other organs. PMID- 3089618 TI - Persisting myocardial sinusoids of both ventricles as an isolated anomaly: echocardiographic, angiographic, and pathologic anatomical findings. AB - The persistence of myocardial sinusoids in both ventricles as an isolated anomaly is described. A 21-year-old patient had progressive heart failure considered as cardiomyopathy of obscure etiology. Two-dimensional echocardiography demonstrated channel-like structures in the thickened myocardium of both hypokinetic ventricles. Angiography showed a honeycomblike inner contour in both ventricles. Autopsy proved the diagnosis of persistent sinusoids in a thickened myocardium. PMID- 3089619 TI - Use of CT in the evaluation of primary cardiac tumors. AB - Two cases of primary cardiac sarcomas diagnosed with CT are presented. CT demonstrated the origin, extent, and potential pathology of the tumors. In both cases CT provided more specific information for diagnosis and treatment planning than the 2D echocardiography. The advantages of CT in the detection of cardiac tumors as well as its potential advantages over 2D echocardiography are also discussed. PMID- 3089620 TI - Isolated external iliac artery aneurysm secondary to cystic medial necrosis. AB - The computed tomographic and angiographic findings of an isolated external iliac artery aneurysm secondary to cystic medial necrosis in a patient without Marfan's disease are demonstrated. A review of the differential diagnosis and surgical treatment of iliac artery aneurysms is presented. The dramatic surgical sequelae in this patient underscore the importance of preoperative consideration of this rare diagnosis. PMID- 3089621 TI - Aortic dissection following coronary artery bypass surgery: diagnosis by CT. AB - We describe an unusual case of aortic dissection causing spinal cord infarction. The dissection arose from an intimal tear at the suture line of a coronary artery bypass graft. CT was used to diagnose the dissection and to demonstrate its extension to the aortoiliac bifurcation and innominate artery and its rupture into the left pleural cavity. The most common causes of intimal tears following cardiac bypass surgery are aortic cross-clamping, aortic cannulation, and injury during suturing of the graft to the aorta. An underlying disease of the aorta such as atherosclerosis, cystic medial necrosis, or aortitis is commonly present. CT is an accurate and safe means of detecting aortic dissections following cardiac surgery, and is also useful in assessing the extent of the dissection and identifying its rupture into the pleural or pericardial cavity. PMID- 3089622 TI - Hepatic artery embolization of experimental hepatic tumors with absolute ethanol. AB - Hepatic artery embolization with absolute ethanol (HAEE) was done in rats and rabbits with experimentally induced liver tumors, and its effects on liver parenchyma and tumors were analyzed microscopically in comparison with those of controls. HAEE with 0.1 ml in rats brought massive tumor necrosis and minimal damage to liver parenchyma. But HAEE with 0.15 ml in rabbits induced moderate to massive necrosis of liver parenchyma with minimal to moderate tumor necrosis. Damage to the intrahepatic bile ductules was also seen in both animals. Many problems should be resolved before clinical use. PMID- 3089623 TI - Infantile hemangioendothelioma: angiographic features and factors determining efficacy of hepatic artery embolization. AB - The angiographic features of infantile hepatic hemangioendothelioma are discussed as well as the role of hepatic artery embolization in its management when more conservative measures have failed. A unique case with portal vein supply of the tumor is presented, and the impact of this angiographic feature is discussed. PMID- 3089624 TI - Angiographic management of arteriocolic fistulae. AB - Two cases of massive lower GI bleeding caused by external iliac artery fistulization to the colon are presented. Both patients had had pelvic malignancy and pelvic irradiation. Angiography is the diagnostic procedure of choice. Our cases were successfully treated with local embolization. PMID- 3089625 TI - A dual-balloon technique for nonoperative removal of retained biliary stones. AB - Retained intrahepatic biliary stones were dislodged with and crushed between two occlusion balloon catheters. Standard angiographic catheters and guide wires with exchange for occlusion balloon catheters can be used in situations where a stone basket cannot, and have certain advantages over Fogarty biliary balloon catheters. PMID- 3089626 TI - Antimanic effect of zotepine. AB - The antimanic effect of zotepine was investigated in 16 patients with manic depressive psychosis or manic schizoaffective psychosis. Zotepine markedly improved manic symptoms in 75% and afforded at least slight improvement in all patients studied. However, in 50%, zotepine caused conversion from mania to depression. The most frequent side effects were dysarthria in 50%, parkinsonian symptoms in 33%, dry mouth in 28%, and sleepiness in 28%. EEG abnormalities were noted in 22% of patients. The antimanic effect of zotepine was enhanced by lithium carbonate; however, concomitant use of zotepine and lithium possibly increased the incidence of EEG abnormalities. The conversion-to-depression effect of zotepine was not inhibited by lithium. Overall, the concomitant use of zotepine and lithium may be important in the treatment of manic psychoses. PMID- 3089627 TI - Safety of helicopter transport and out-of-hospital intravenous fibrinolytic therapy in patients with evolving myocardial infarction. AB - Of 150 consecutive patients with acute myocardial infarction transported by helicopter for acute intervention, 55 had intravenous thrombolytic therapy (tissue plasminogen activator in 12, streptokinase in 43) initiated prior to transfer. Patients were transported 55 +/- 10 ground miles in 17 +/- 6 minutes and no patient died or experienced bleeding or hemodynamic instability during transfer. Patients receiving thrombolytic therapy had a higher incidence of arrhythmias during transit compared to the untreated group, ventricular tachycardia in six and third-degree atrioventricular block in one compared to ventricular tachycardia in one patient, respectively (p = 0.005). However, these arrhythmias were transient and did not require cardioversion, temporary pacing, or further antiarrhythmic medical treatment. Chest pain was relieved or decreased more frequently in the patients receiving thrombolytic therapy vs. those untreated; 21 of 55 vs. 21 of 95 respectively (p = 0.04). Immediate coronary angiography confirmed a higher incidence and more complete infarct vessel patency (34/55 vs. 30/95) in the patients receiving tissue plasminogen activator or streptokinase (p less than 0.001). Thus, helicopter transfer of patients with evolving myocardial infarction is safe, and early initiation of thrombolytic therapy is associated with increased infarct vessel patency and benign reperfusion arrhythmias. PMID- 3089628 TI - The dissociation of nuclear and centrosomal division in gnu, a mutation causing giant nuclei in Drosophila. AB - We describe a recessive, maternal-effect lethal mutation of Drosophila, gnu. gnu uncouples nuclear division from many cytoplasmic events of mitosis in the Drosophila embryo. Embryos from homozygous females are defective in nuclear division, but not in DNA replication, and therefore develop a small number of giant nuclei. Centrosomes divide independently of nuclear division and migrate to the surface of the syncytial blastoderm. There they nucleate microtubules into asters, which appear normal at first but become very large. Only later, when the giant nuclei begin to break down, are spindles sometimes formed. The cortical actin of these embryos develops into a characteristic network. PMID- 3089630 TI - New trends in urologic management of spinal cord injured patients. AB - We have attempted to address some of the current issues and new trends in the urologic management of SCI patients. Although tremendous progress has been made with these patients, resulting in a significant lowering of renal morbidity and mortality, there is still room for improvement. Newer methods of bladder management and refinements of older techniques are being sought. Progress in treating urinary infections should occur through development of new antibacterials and through improved understanding of host-bacterial interactions. Research into these problems and the general management of the neurologic dysfunction in SCI offers the hope of an even brighter future for these severely disabled patients. PMID- 3089629 TI - Flow cytometric determination of cell cycle parameters of V79 cells by continuous labeling with bromodeoxyuridine. AB - A simple method with which to determine the cell cycle parameters, TG1, TS and TG2M (the durations of the G1, S and G2 + M phases) is described. V79 Chinese hamster lung cells were used to evaluate the method. After continuous labeling with bromodeoxyuridine (BrdU), V79 cells were stained with anti BrdU-monoclonal antibody with FITC (fluorescein isothiocyanate) and with PI (propidium iodide). The individual cells were checked by flow cytometry for green and red fluorescences whose signal intensities corresponded to the BrdU and cellular DNA contents. The durations of G1, S and G2 + M phases of V79 cells were determined by measuring the cell fractions containing the nonlabeled G1, labeled S and nonlabeled G2 + M phases. The reliability of this method is discussed. PMID- 3089631 TI - Effects of flavonoids and related compounds from mulberry tree on arachidonate metabolism in rat platelet homogenates. PMID- 3089633 TI - Effects of some phenolics on the prostaglandin synthesizing enzyme system. PMID- 3089632 TI - In vitro oxidation of the 8-hydroxyquinoline moiety with metabolic activation system to a mutagenic quinoloquinone compound of lavendamycin analogs. PMID- 3089634 TI - Isolation and structural elucidation of a new lipoxygenase inhibitor from gardeniae fructus. PMID- 3089636 TI - [Isolation of the Fomede virus from Chiroptera, Nycteris nana, in the Republic of Guinea]. AB - In October 1978, a new virus named Fomede was recovered from the bat, Nycteris nana, during the studies of arbovirus infections in Guinea (West Africa). When the virus was tested, it did not fit any prototype patterns. These findings have led to a presumption that the ch. s. 654 strain of virus is a previously unknown virus due to its biological, physico-chemical and antigenic patterns. PMID- 3089635 TI - Substitution of Ser61----Gly61 in human apolipoprotein C-II does not alter its activation of lipoprotein lipase. AB - Lipoprotein lipase (LpL) activity is enhanced by apolipoprotein C-II (apoC-II), a 79 amino acid residue peptide. The minimal apoC-II sequence required for activation of LpL resides between residues 56-79. To determine the possible role of an acyl-apoC-II intermediate involving Ser61 in enzyme catalysis, a synthetic peptide of apoC-II containing residues 56-79 was synthesized and compared to the corresponding peptide with serine at position 61 being substituted with glycine. With two different LpL assay systems, both peptides enhanced enzyme activity. Since glycine does not contain a hydroxyl group, these results rule out the possibility that an acyl-apoC-II intermediate with Ser61 is required for enzyme activation. PMID- 3089637 TI - [ Subtypes of HBsAG in Morocco: general distribution in HBsAG carriers in Casablanca in terms of their clinical state. Relations with the markers of the HBe system]. AB - HBs Ag subtypes ad and ay were determined by counter-electrophoresis (CEP) among 301 persons from Casablanca found HBs Ag positive by CEP: 147 were asymptomatic HBs Ag carriers and 154 were patients with acute or chronic hepatitis. w and r determinants were investigated among 82 from them only. HBe antigen and antibody (AB) were investigated by gel double immunodiffusion among 294 persons. Into the whole population, the prevalence of ad and ay subtypes was respectively 20 and 80%. This distribution, intermediate between those reported in West Europe and West Africa, was in agreement with data previously reported by others in the Maghreb, but differing from these ones in the distribution of w and r determinants. ayr subtype was found dominant (39%) and adw rare (2.4%), the prevalences of adr and ayw being intermediate (25-30%). Among asymptomatic HBs carriers and patients only adr and ayr distribution differed: in the formers, adr was dominant and ayr rare and, in contrast, ayr was frequent and adr rare among patients. Elsewhere, some findings were in agreement with previously reported data by others, such as the frequent association of ad to chronic liver disease or long-term HBs Ag carriage, ay being rather associated to short-term carriage, the frequency of HBe Ab in ad subtype and the presence of ay among almost all HBs positive haemodialysed patients. PMID- 3089638 TI - [Bilharziasis caused by Schistosoma mekongi along the Mekong and its affluents Mun and Tonle Sap. Apropos of 2 cases observed at the University Hospital Center of Tours]. AB - The authors report two cases of Schistosomiasis mekongi observed in Laotian people living in Touraine. Discussions about epidemiology, clinical, biology and treatment are taken up. PMID- 3089639 TI - Metabolism of diethylnitrosamine by nasal mucosa and hepatic microsomes from hamster and rat: species specificity of nasal mucosa. AB - The oxidative metabolism of diethylnitrosamine (DEN) was investigated by acetaldehyde determination using microsomes from nasal mucosa and liver of Sprague-Dawley rats and nasal mucosa and liver of Syrian Golden hamsters, to establish the role of metabolic activation in the organo-targets for the carcinogenicity of the nitrosamine. The hepatic microsomal de-ethylation of DEN followed simple and biphasic Michaelis-Menten kinetics for rat liver and hamster liver, respectively. Both de-ethylations were inducible by phenobarbital (PB) and the DEN-de-ethylase activities and the Michaelis constants were determined. Microsomes from hamster liver showed a higher metabolic rate (Vmax) and a better affinity (Km) towards DEN with respect to microsomes from rat liver. In hamster, microsomes from nasal tissue biotransformed DEN at a rate and affinity quite similar to those of liver. In contrast, nasal mucosa of rat metabolized DEN poorly. The effect of metyrapone, a classical inhibitor of P-450 monooxygenases, on DEN de-ethylation was studied. It inhibited both hepatic and nasal DEN-de ethylase activity, with greater affinity towards the latter. In addition metyrapone had a greater inhibitory effect on the hepatic P-450 isozymes induced in PB-treated animals. These results correlate well with the organotrophy of DEN carcinogenesis in the nasal region of hamster, but not of rat. They suggest that for the nose the metabolic activation of DEN in situ is necessary to elicit its carcinogenic effect. PMID- 3089640 TI - Prostaglandin H synthase-mediated bioactivation of the amino acid pyrolysate product Trp P-2. AB - We report evidence that the mutagen and carcinogen 3-amino-1-methyl-5H pyrido[4,3b]indole (Trp P-2) is a substrate for co-oxidation by prostaglandin H synthase (PHS) in ram seminal vesicle (RSV) microsomes. Trp P-2 serves as a reducing cofactor for the hydroperoxidase activity of PHS as shown by the concentration-dependent inhibition of the hydroperoxidase catalyzed incorporation of molecular oxygen into phenylbutazone. Spectral data suggest that this metabolism results in disruption of the double bond conjugation within the nucleus of the molecule. A single metabolite peak which was dependent upon arachidonic acid and substrate concentration was separated from the parent compound by h.p.l.c. following incubation with RSV microsomes. Co-oxidation of Trp P-2 produced reactive intermediates which bound covalently to microsomal protein (9 nmol/mg) and to calf thymus DNA (475 pmol/mg). Binding was inhibited by indomethacin, and supported by substitution of hydrogen peroxide for arachidonic acid. These data suggest a possible role for PHS in the in situ activation of Trp P-2 to its ultimate carcinogenic form in tissues which contain PHS. PMID- 3089641 TI - Cellular distribution of lysosomal hydrolase activities in the regenerating rat liver. AB - Cathepsins B and D, beta-galactosidase, and acid phosphatase activities were found to be decreased in the regenerating rat liver, the reduction being maximal around the peak of hepatocyte mitoses (30 h). To investigate whether these changes could be heterogeneously distributed among hepatic cells, total cell populations from control or two-thirds hepatectomized rat livers were dissociated by the collagenase perfusion technique and analysed by different procedures. Isopycnic centrifugation in a Metrizamide gradient satisfactorily resolved hepatocytes and non-parenchymal cells from control animals but was not adequate when applied to 30-h regenerating liver cells. Colchicine treatment of the hepatectomized animals, resulted in substantial accumulation of phase M hepatocytes. Subpopulations considerably enriched in fast-sedimenting phase M cells were obtained by sedimentation at 1 g of the total liver cell population, and subsequently analysed by isopycnic equilibration. Phase M-hepatocytes were shown to have markedly reduced levels of beta-galactosidase, acid phosphatase, and cathepsin B activities in comparison, not only with control hepatocytes, but also with those parenchymal cells which were not metaphase-arrested in the same regenerating livers. Therefore, in partially-hepatectomized rats, hepatocytes progressing up to metaphase in the first mitotic cycle exhibited a selective depletion of lysosomal enzyme activities. The mechanism(s) underlying this change remain(s) presently unknown. PMID- 3089643 TI - An automated method for the determination of Cu,Zn-superoxide dismutase in plasma and erythrocytes using an ABA-200 discrete analyzer. AB - An automated enzymatic method is described for the determination of Cu,Zn superoxide dismutase (SOD) in plasma or erythrocytes using the xanthine-xanthine oxidase and cytochrome C coupled assay. This method was adapted to an Abbott ABA 200 discrete analyzer. Coefficients of variation for within-run and day-to-day analyses were less than 5%. Only 2.5 muL of serum or erythrocyte extract is required so a capillary tube sample of blood (70 muL) is sufficient for the assay. Recovery of added SOD ranged from 92 to 101%. The method reported here is practical for use in a clinical chemistry laboratory for monitoring changes in this enzyme, which is a sensitive early indicator of alterations in copper status. PMID- 3089642 TI - Inhibition of human platelet aggregation and cytoplasmic calcium response by calcium antagonists: studies with aequorin and quin2. AB - Calcium antagonists inhibit platelet aggregation, but whether this action is due to inhibition of the effect of agonists on cytoplasmic ionized calcium concentration is unknown. We studied this problem by loading gel-filtered platelets with either quin2 or aequorin and stimulating them with epinephrine, arachidonate, thrombin, the calcium ionophore A23187, 1-oleoyl-2-acetyl glycerol, or adenosine diphosphate in media with or without extracellular calcium. In response to all of these agonists, aequorin indicated an increase in cytoplasmic calcium that accompanied or preceded platelet aggregation. In calcium-containing media, verapamil, nifedipine, and diltiazem inhibited these effects in a concentration-dependent fashion, except for those produced by thrombin and A23187. Removal of extracellular calcium with EGTA reduced the calcium response to arachidonate, adenosine diphosphate, and 1-oleoyl-2-acetyl glycerol, and the calcium response and aggregation were further inhibited by the calcium antagonists. In general, strong inhibition of the aequorin cytoplasmic calcium signal by approximately 100 microM concentrations of nifedipine, verapamil, and diltiazem was correlated with inhibition of platelet aggregation, but high concentrations of the inhibitors were required. Since inhibition by the calcium antagonists of the cytoplasmic calcium response and aggregation exceeded the effect of simple removal of extracellular calcium, these drugs may affect internal redistribution of calcium in human platelets. PMID- 3089644 TI - Assessment of immunochemical methods for determining low concentrations of albumin in urine. AB - Four immunochemical methods (radioimmunoassay, RIA; radial immunodiffusion, RID; immunoturbidimetry, IT; enzyme-linked immunosorbent assay, ELISA) for measuring urinary albumin at low concentrations were assessed for their assay characteristics and practicability. Precision and accuracy were comparable between the methods when studied individually. We made a method comparison, with RIA as reference, using urine samples from diabetic patients with albumin concentrations ranging from 1 to 120 mg/L. There was no significant systematic difference between RID and RIA, but IT and ELISA gave consistently lower values than RIA, the mean differences being 1.8 (p less than 0.01) and 9.7 mg/L (p less than 0.001), respectively. Random error, compared with that for RIA, was in increasing order: RID (residual SD = 3.8 mg/L); IT (4.3 mg/L); ELISA (7.3 mg/L). The difference between the methods increased with the albumin concentration. Operational cost was highest with IT, lowest with RIA. Capital cost was highest with RIA and lowest with RID, which required most technical skill. ELISA had intermediate overall costs. PMID- 3089645 TI - Metabolic conversion of L-[U-14C]phenylalanine to respiratory 14CO2 in healthy subjects, phenylketonuria heterozygotes and classic phenylketonurics. AB - Ten healthy volunteers, 12 classic phenylketonuria (PKU) heterozygotes, and 5 classic phenylketonurics have been loaded orally with a mixture of 5 microCi of L [U-14C]phenylalanine plus 25 mg/kg of L-[2H5]phenylalanine. For 3 h thereafter, carbon-14 activity in expired air and total carbon dioxide were measured continuously and the levels of L-phenylalanine and L-tyrosine in plasma were determined in six blood samples. After 3 h, 15.1 +/- 2.1% of the applied dose of radioactivity was recovered in the expired air of the healthy subjects, compared to 10.1 +/- 2.2% for PKU heterozygotes and 0.32 +/- 0.18% for classic phenylketonurics. The integrated activity expired provides a discrimination between normals and PKU heterozygotes with a classification error of about 13% compared to an error of about 9% based on the fasting L-phenylalanine over L tyrosine ratio. A combination of these two parameters in a two-dimensional discriminatory analysis reduces the classification error to less than 1%. An intraindividual correlation between the absolute activity expired and the formation of L-[2H4]tyrosine formed is shown, confirming that ring hydroxylation of L-phenylalanine to L-tyrosine is mandatory in the catabolism of L phenylalanine to carbon dioxide. PMID- 3089646 TI - Seizure control by mesothalamic reticular stimulation. AB - A 53 year old woman with chronic back pain and headaches also was considered to have a reticular formation generated "absence status." Both the chronic pain and the absence status were relieved by electrical stimulation in the mesothalamic reticular formation. The various psychologic and physiologic factors contributing to the patient's illness were analyzed and presented to demonstrate the progression of the illness. The discussion considers electrical "mini-discharges" in the reticular formation as the generator of the absence status and associated chronic pain. Therapeutic reticular stimulation electrically "jams" the reticular "mini-discharge" generator and thereby alleviates the absence attacks and pain. PMID- 3089647 TI - The treatment of laryngeal stenosis using the CO2 laser. AB - Conventional open treatment for laryngeal stenosis involves major surgery. Seventeen patients with various pathologies, who needed tracheostomy to relieve their laryngeal stenosis, have been assessed following endoscopic treatment with the CO2 laser. Following an initial direct laryngoscopy, 3 of the patients were considered to be unsuitable for laser treatment. The remaining 14 patients had the stenosed area excised until it was felt that the airway was sufficiently patent to allow closure of the tracheostomy. Eight of the patients were successfully decannulated. The CO2 laser may be used endoscopically to treat certain patients with laryngeal stenosis, who would otherwise require open operation or a permanent tracheostomy. PMID- 3089648 TI - Preoperative swabs for the treatment of draining ears after middle ear surgery. AB - The value of a preoperative swab for the treatment of postoperative infection after middle ear surgery was investigated. In a selected group of 80 patients with postoperative infection a preoperative swab was available, and the variability was analysed for each species. The well-known pathogens Pseudomonas aeruginosa, Staphylococcus aureus, Proteus and Escherichia coli showed good correlation between pre- and postoperative swabs. In contrast to this all other species found in preoperative swabs were of little value postoperatively. This observation is important for the treatment of infection after middle ear surgery, and should be considered if prophylactic antibiotics are planned. PMID- 3089649 TI - Regulation of macrophage accessory cell activity by mycobacteria. II. In vitro inhibition of Ia expression by Mycobacterium microti. AB - In our preceding study, we showed that infection of mice with Mycobacterium microti leads to a dramatic increase in Ia expression on local inflammatory macrophage populations. However, the majority of these cells did not contain intracellular organisms. To evaluate the effect of parasitism of macrophages by M. microti, Ia-induction experiments were performed in vitro. We show here that Ia expression is increased on peritoneal macrophages treated with either crude lymphokine preparations or recombinant gamma-interferon (gamma-IFN) and that this expression is suppressed by M. microti in a dose dependent fashion. The degree of suppression varied between macrophage populations and could be achieved to a lesser extent with killed organisms. It was partially reversed with indomethacin but only poorly so at high infection levels. Inhibition of Ia expression may be of importance in the generation and maintenance of chronic infection. PMID- 3089650 TI - Natural killer activity in patients with acute viral hepatitis. AB - Using the natural killer (NK) sensitive K562 cell line, enhanced NK cell cytotoxicity was demonstrable early in the course of acute hepatitis B while normal values were obtained in patients studied during convalescence. No evidence of enhanced NK activity was instead obtained in the course of acute non-A, non-B hepatitis. Serum levels of alpha-interferon, as determined by radioimmunoassay (RIA), were significantly increased in patients with acute hepatitis B showing enhanced NK cell activity but not in those with acute non-A, non-B hepatitis and normal NK cell activity. These results suggest that natural cytotoxicity may play a role early in the course of acute hepatitis type B, before antigen-specific T lymphocytes become fully operative. PMID- 3089651 TI - Evidence for enhanced interleukin 2 (IL-2) secretion and IL-2 receptor presentation by synovial fluid lymphocytes in rheumatoid arthritis. AB - Synovial fluid lymphocytes (SFL) and peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA) and reactive oligoarthritis were investigated for activated T cells (Ia+SIg-), IL-2 receptor bearing cells (Tac+) and IL-2 production in vivo and in vitro. In contrast to negative results with blood, the synovial fluid of the arthritic joints contains considerable amounts of IL-2 activity (median: 11.8 mu/ml), elevated proportions of Ia+SIg- activated T cells (median: 12.5%) and of IL-2 receptor bearing cells (median: 2.5%). In vitro, after stimulation with several Concanavalin A (Con A) doses, SFL develop proportions of IL-2 receptor cells comparable to PBL. Furthermore, they produce higher values of IL-2 activity than comparable PBL cultures. The proportions of Ia+SIg- activated T cells increase only moderately after Con A stimulation compared to in vivo data, indicating different activated T cell subsets in the synovial fluid (Ia+SIg-, Tac+). The findings are discussed as an expression of an acute hyperactivation of lymphocytes in an inflamed joint. PMID- 3089653 TI - Endothelium-dependent vasodilatation in bovine coronary arteries: calcium dependence and inhibition by proadifen. AB - Vasodilator responses were examined in bovine coronary artery rings preconstricted with the thromboxane-mimetic, U46619. A23187 produced endothelium dependent vasodilatation that was abolished in calcium-free solution. In contrast, endothelium-dependent vasodilatation produced by arachidonic acid was not altered in calcium-free solution. In calcium-free solution, indomethacin (10 mumol/l) did not affect arachidonate-induced relaxations whereas BW755C (100 mumol/l) reduced relaxations to low concentrations of arachidonate, and proadifen (SKF-525A, 1 mmol/l) abolished them at all concentrations. Endothelium independent relaxations produced by glyceryl trinitrate were not affected by proadifen (1 mmol/l). It is clear that arachidonic acid bypasses a calcium dependent step in the release of endothelium-derived relaxing factor, perhaps acting as an intermediate precursor. The data support the hypothesis that a cytochrome P-450 mono-oxygenase may also be involved. PMID- 3089652 TI - Scl-95/100: doublet of endothelial marker autoantigens in progressive systemic sclerosis. AB - Thirteen out of 60 sera (22%) from patients with progressive systemic sclerosis reacted by immunoblotting with a doublet of 95 kD and 100 kD proteins in endothelial cells of human and bovine origin. Reactivity with the doublet was not seen in any of 125 control sera. The endothelial doublet was localized to the nucleus by immunoblot reactivity with nuclear subcellular fractions but not with mitochondrial, microsomal or soluble subcellular fractions. In HEp-2 cells and in HeLa cells, positive sera reacted with the 100 kD antigen, but not with the 95 kD antigen. Identical immunoblot reactivity was obtained with a standard reference serum containing anti-scl-70 activity by immunodiffusion. All positive sera also reacted with cell nuclei by indirect immunofluorescence and 10 gave anti-scl-70 reactivity by immunodiffusion. These observations suggest that the 95 kD/100 kD doublet may be a larger form of the Scl-70 autoantigen. PMID- 3089654 TI - Evolution of renin. AB - New gene data for three aspartyl proteases (human renin, mouse renin and human pepsin) permitted closer analysis of the gene duplication and fusion hypothesis for the evolution of this family of enzymes. Alignment of sequences in the hemilobes of human pepsin revealed only weak homology in amino acid sequences. Nucleotides were, however, more homologous. Splice junctions between putative duplicated exons did not match. Repeated sequences in the human renin gene were detected by hybridization with total human DNA labelled with 32P. These were not, however, consistent with unequal crossing-over between repeated sequences of an ancestral gene having occurred. The data thus provide no immediate support for the gene duplication and fusion hypothesis. The symmetry in structure of an aspartyl protease may arise from the tendency of hydrophilic amino acids to be encoded at splice junctions. This would divide a molecule comprised mainly of beta-sheets into roughly superimposable domains. PMID- 3089656 TI - Characterization of functional T-cell lines derived from MRL mice. AB - In an effort to characterize further the role of T cells in the autoimmune disease of MRL/Mp-lpr/lpr (lpr) mice, continuous cell lines were established from spleen and lymph nodes using EL-4 lymphoma supernatants as a source of T-cell growth factor(s). Five lines were derived from lpr spleen and lymph nodes, and an equal number from MRL/Mp- +/+ (+/+). All of the lines lost their alloreactivity after a short time in culture. Surprisingly, every line manifested marked proliferation in response to autologous irradiated spleen cells. This response was restricted to I-Ak, as it was blocked with monoclonal anti-I-Ak antibodies, and as B10.A(4R) accessory cells were stimulatory while B10.A(3R) were not. There was no difference in the degree of stimulation from lpr accessory cells compared to that in those from +/+ or other H-2k mice. The T-cell lines bore Thy-1, Ly-1, L3T4, and 7D4 (interleukin 2 (IL-2) receptor), but lacked Ly-2 and surface Ig. They proliferated in response to both conventional and recombinant DNA-derived IL 2. When cocultured with Ia-identical B cells, the T-cell lines provoked B-cell division and antibody production. The cells also caused intense proliferation when cultured with freshly isolated lpr (but not +/+) lymph node cells. The results indicate that lpr lymphoid tissue contains functional T cells reactive to autologous Ia molecules and capable of inducing both B-cell activation and the proliferation of lpr lymphocytes. Such cells may be of importance in inducing hypergammaglobulinemia, autoantibody production, and lymphoproliferation in these SLE mice. PMID- 3089655 TI - Abnormal B-cell function in hemophiliacs treated with cryoprecipitate and factor VIII and IX concentrates. AB - B-Cell function was evaluated in a group of 43 patients with factor VIII or factor IX deficiency. Thirty had been treated primarily with cryoprecipitate and 13 with concentrates of factor VIII or IX. Serum immunoglobulin G levels were found to be diffusely elevated; however, the absolute number of mature B cells in peripheral blood was normal. B-Cell function as measured by testing mitogen induced proliferation and and immunoglobulin secretion by plaque-forming cells (PFC) in vitro was reduced. Coculture experiments suggested that these abnormal B cell responses might be secondary to increased suppressor T-cell activity, which was found more frequently in patients seropositive for antibody to lymphadenopathy-associated virus. Both seronegative and seropositive patients had reduced responses in the proliferative and PFC assays, but the lowest PFC responses occurred in the seropositive group. PMID- 3089657 TI - Thrombosis and immune disorders. AB - The purpose of this review has been to draw the attention of clinicians towards the possibility that some of the patients they are treating for thrombosis may have an underlying immune disturbance. This could involve functional abnormalities of the complement system (as in acquired angioneurotic oedema or in paroxysmal nocturnal haemoglobinuria), or cell-mediated immunological damage to the vessel wall (as in Behcet's syndrome or Buerger's disease), or the presence of circulating antibodies (the lupus anticoagulant or antibodies to heparin). While obviously our knowledge on most aspects is still very incomplete, the awareness of the association of thrombosis with certain immune disorders should encourage further detailed studies of mechanisms and enhance our understanding of the role of blood constituents and the vessel wall in thrombogenesis. PMID- 3089658 TI - Deficiency of apolipoproteins A-I and C-III and severe coronary heart disease. AB - A 55-year-old woman with severe coronary arteriosclerosis and skin xanthomas is described. The patient had a normal total cholesterol level of 168 mg/dl. Her level of high-density lipoprotein cholesterol was markedly reduced (3 mg/dl). On apolipoprotein analysis, apolipoproteins A-I and C-III were not detectable, and the level of apolipoprotein A-II was found to be at a low level (3.5 mg/dl). This case may possibly belong to a distinct new disease entity of deficiencies of apolipoprotein A-I and C-III in which coronary arteriosclerosis appears prematurely and severely. PMID- 3089659 TI - Anti-cardiolipin antibodies and the lupus anticoagulant. PMID- 3089660 TI - Outer membrane proteins of Neisseria meningitidis: structure and importance in meningococcal disease. AB - Meningococcal meningitis is a serious disease with a high incidence in children. Since meningococcal surface structures play a role in invasion of the host and initiation of disease, host defense mechanisms are directed against these meningococcal structures. All virulent meningococci are encapsulated, but other factors are also involved. Only certain serotypes of group B and group C meningococci are strongly associated with disease. Our studies have been directed toward a better understanding of the structure of the meningococcal cell surface. There are five classes of major outer membrane proteins exposed on the cell surface, designated class 1 through 5, based in part upon the protein's molecular weight. Using monoclonal antibodies we have shown that antibodies to the class 1, 2 and 5 proteins of serotype 2 are bactericidal and therefore probably protective. Convalescent sera of meningococcal disease patients have elevated antibody levels to each of these classes of proteins. Outer membrane protein vaccines have been prepared, and clinically evaluated in adults and children as young as 6 mo of age. The vaccines induce serotype specific bactericidal antibodies in all age groups, but they induced lower levels in young children. We are now working to improve the immune response of children through the use of aluminium adjuvants. PMID- 3089662 TI - A neonatal mouse model of meningococcal disease. AB - Neisseria meningitidis, the meningococcus, remains a major cause of bacterial meningitis. Previously developed animal models for this infection do not adequately mimic its natural pathogenesis in humans. We have investigated a number of different potential animal models and describe a neonatal mouse model. Meningococci were instilled intranasally into five-day-old mice; invasiveness was measured by blood cultures and cisternal puncture, and colonization was determined by nasal cultures. Fifty two percent of mice became bacteremic after instillation of strains which are virulent for humans. Human carrier strains were avirulent in this model. Iron dextran enhanced the nasal colonization, invasiveness and mortality due to disease-associated isolates but had no effect on carrier strains. Colonization rates were similar for all strains. There was a marked age-related change in susceptibility to infection which was inversely correlated with levels of serums C3. Immunization of Swiss CD1 dams with N. meningitidis serotype 2 vaccine protected their litters from meningococcal infection. Protective levels of serum antibody were acquired by neonatal mice after suckling immunized dams. The neonatal mouse meets most of the criteria for an appropriate animal model for meningococcemia. PMID- 3089661 TI - Role of Pseudomonas aeruginosa extracellular enzymes in lung disease. AB - A variety of approaches have been employed in an attempt to assess the role of P. aeruginosa extracellular factors in lung infections due to this organism. Isogenic mutants, deficient in single virulence determinants, have been compared to parental strains in a variety of experimental animal models. Purified virulence factors have been instilled into the lungs of experimental animals in order to demonstrate comparable histopathological changes to those which occur during human infections. Serum antibody levels to various extracellular virulence factors have been measured in different patient populations, and inactivated virulence determinants have been tested for their ability to act as protective immunogens in animal model infections. The results from these studies suggest that P. aeruginosa extracellular factors including exotoxin A, proteases, hemolysins and exoenzyme S may play a significant role in the pathogenesis of P. aeruginosa lung infections. PMID- 3089663 TI - [A case of type III (adult) GM1-gangliosidosis that improved markedly with trihexyphenidyl]. PMID- 3089664 TI - [Myotonic dystrophy with transverse myelopathy caused by ossification of the posterior longitudinal ligament--report of two cases]. PMID- 3089665 TI - Cost-appropriateness of whole body vs limited bone imaging for suspected focal sports injuries. AB - Bone imaging has been recognized as a useful diagnostic tool in detecting the presence of focal musculoskeletal injury when radiographs are normal. A retrospective review of bone images in a small number of amateur athletes indicates that secondary injuries were commonly detected at sites different from the site of musculoskeletal pain being evaluated for injury. While a larger study will be necessary to confirm the data, this review suggests that it is medically justified and cost-appropriate to perform imaging of the entire skeleton as opposed to imaging limited to the anatomic site of pain and suspected injury. PMID- 3089666 TI - Treatment of diabetes in pregnancy. PMID- 3089667 TI - The treatment of psychiatric disorders in pregnancy and the puerperium. AB - Although few psychotropic drugs are known to be teratogenic or to have adverse effects on the developing fetus or neonate, no psychotropic drug is of proven safety. It is therefore very important that psychotropic medication should not be prescribed lightly during pregnancy or lactation and that such drugs should be prescribed only where there are positive indications for their use. Close collaboration between obstetrician and psychiatrist is recommended before treatment of a mental illness with psychotropic medication. Breast feeding should not routinely be suspended in mothers who require psychotropic medication. There is an adequate range of psychotropic drugs available to safely treat the pregnant or lactating woman who is mentally ill. PMID- 3089668 TI - Encainide disposition in patients with chronic cirrhosis. AB - The antiarrhythmic agent encainide undergoes extensive first-pass hepatic metabolism after oral dosing. The active metabolites O-desmethylencainide and 3 methoxy-O-desmethylencainide are formed in subjects who are extensive metabolizers (EMs), a phenotypic trait that cosegregates with that of debrisoquin. Because of the possibility that drug metabolism is altered by liver dysfunction, the disposition of encainide and its metabolites was studied in six such EMs with cirrhosis and compared with that in eight normal subjects of the same phenotype. Patients with cirrhosis had lower systemic and oral clearances of encainide, resulting in a threefold increase in oral bioavailability. The plasma concentration of encainide was significantly higher among the patients with cirrhosis, whereas the plasma levels of the respective metabolites were comparable with those in normal subjects, resulting in no change in the patient's ECG intervals. Encainide is, therefore, an example of a drug in which cirrhosis causes a three- to fourfold increase in parent drug concentrations. However, because no change occurs in the levels of the pharmacologically active metabolites, dosage adjustment is probably not required in patients with cirrhosis. PMID- 3089669 TI - Valproate hydroxylation by human fetal tissues and embryotoxicity of metabolites. AB - The oxidative biotransformation of sodium valproate was studied in liver, lung, brain, and adrenal homogenates from human conceptuses with gestational ages ranging from 50 to 77 days. Analyses of metabolites by GC/MS indicated the formation of 3-hydroxy-, 4-hydroxy-, and 5-hydroxyvalproic acid, with hydroxylation occurring preferentially at the 4- position. The adrenal homogenate was consistently the most active fetal tissue studied, with rates of hydroxylation similar to those in rat and macaque liver homogenates. Reaction rates in the fetal adrenal homogenate were approximately four times those in fetal liver and approximately 10 times the rates of the same reactions measured in fetal brain and lung. Although valproic acid itself (0.8 mmol/L) was highly embryotoxic to cultured whole rat embryos, none of the hydroxylated metabolites produced by human fetal tissues exhibited significant embryotoxicity at equimolar concentrations. This suggests that hydroxylation of valproic acid in human fetal tissues is a process of detoxification, and implies that valproic acid is a direct-acting teratogen. PMID- 3089670 TI - Dose effects of alfentanil in human analgesia. AB - Alfentanil, a rapidly acting opioid, was given in subanesthetic doses to 10 subjects in a laboratory setting. Analgesia was assessed from the subjects' responses to painful dental stimulation. A subjective pain report (PR) and brain evoked potential (EP) amplitude were obtained repeatedly before and after injection on each of 4 testing days, on which the following intravenous doses were administered: 0 (saline solution), 5, 10, and 15 micrograms/kg. Significant dose effects were observed for EP amplitude during but not beyond the distributional t1/2 of the drug, but significant effects on the PR extended beyond this time point. Mean volume of distribution, total body clearance, and distribution t1/2 did not differ significantly across the doses of alfentanil. Strong correlations between each effect measure and plasma drug concentration were observed at all doses and were significant at P less than 0.01. The EP scores tracked the distribution of alfentanil very closely, but the correlation between EP amplitude and plasma alfentanil concentration was lower during the elimination phase. In contrast, the PR effects closely tracked the elimination of alfentanil but not its distribution. These findings suggest that EP amplitude and the PR represent two different central effects in opioid analgesia. PMID- 3089671 TI - Monoclonal antibodies produced against murine tyrosinase identify pigmented human melanocytes. AB - Three monoclonal antibodies were recently produced in our laboratory that specifically identify murine tyrosinase, the enzyme critical to the production and regulation of melanin pigment in mammals. These antibodies are now shown with indirect immunofluorescence to cross-react with human tyrosinase in normal, preneoplastic, and transformed melanocytes. All epitopes specifically recognized on the mature, glycosylated form of murine tyrosinase are also present on the human enzyme, which suggests that mammalian tyrosinase is a highly conserved protein. These monoclonal antibody reagents are useful as sensitive, highly specific probes to identify pigmented human melanocytes both in vivo and in vitro. PMID- 3089672 TI - IgM-kappa-lambda biclonal gammopathy elucidated by immunofixation electrophoresis. AB - A patient with alcoholism-related illness was found to have a rarely encountered biclonal gammopathy with IgM-kappa and IgM-lambda components. The para-protein bands were readily identified by immunofixation electrophoresis but were not by conventional immunoelectrophoresis. This patient is most appropriately classified as a biclonal gammopathy of undetermined significance, since no cause for this abnormality was found. The literature on biclonal IgM-kappa-lambda gammopathy is reviewed. PMID- 3089673 TI - [Accumulation of 99mTc-methane diphosphonic acid (MDP) in both breasts in prolactinoma]. PMID- 3089674 TI - Long term experience with oral gold in psoriatic arthritis. PMID- 3089675 TI - British standard for human serum vitamin B12. AB - Seven laboratories took part in a collaborative study of an ampouled preparation of normal serum labelled 81/563. Each laboratory calibrated the preparation in terms of pure cyanocobalamin by use of Euglena assay. The inclusion of pernicious anaemia serum in the study and additional tests for safety and stability indicated that 81/563 would be a suitable standard for diagnostic testing. In 1985 the National Biological Standards Board established the preparation as the British Standard for Human Serum Vitamin B12 and, with the agreement of participants in the study, assigned it a potency of 320 picograms per ampoule. PMID- 3089676 TI - Mechanisms and management of respiratory failure. AB - Management of respiratory failure is a complex endeavor that requires consideration of diverse etiologies and pathophysiology. Future investigation may lead to specific pharmacologic interventions of greater efficacy. In the meantime, careful attention to basic tenets of pathophysiology, supportive care, and reversal of underlying pulmonary insults is the foundation of successful therapy. PMID- 3089677 TI - Predicting demand for accident and emergency services. PMID- 3089678 TI - Sulphoxidation of S-carboxymethyl-L-cysteine in the rhesus monkey (Macaca mulatta), cynomologus monkey (Macaca fascicularis), African green monkey (Cercopithecus aethiops) and the marmoset (Callithrix jacchus). AB - The metabolic pathways giving rise to the urinary metabolites of S-carboxymethyl L-cysteine have been identified for the rhesus, cynomologus, African green and marmoset species of monkey. The formation of a sulphoxide metabolite from the sulphide precursor is a reaction important in these species. The metabolic profile displayed by the marmoset was distinct from the three Old World species, with the rhesus and cynomologus being similar to man. PMID- 3089679 TI - Classification of malnutrition by statistical analysis of quantitative two dimensional gel electrophoresis of plasma proteins. AB - An attempt to use the relative concentrations of major plasma proteins for clinical assessment of severe malnutrition is described. Quantitative two dimensional gel electrophoresis was used to measure the concentrations of 24 major proteins in small aliquots of plasma obtained from children, aged 0 to 3 years, who were patients and outpatients in Liberian hospitals. Fifteen had a clinical diagnosis of kwashiorkor, 36 were diagnosed with marasmus, and 18 were controls. There were also 5 controls from the United States. The individuals were placed in six groups; kwashiorkor, kwashiorkor who died during treatment, marasmus, marasmus who died, Liberian controls, and U.S. controls. The amount of protein in each spot in the two-dimensional gels was estimated by measuring bound stain using a laser scanner and computerized image analysis. We found very low serum transferrin levels in malnourishment, in agreement with reports from other investigators. All of the data for 24 protein variables were pooled for factor analysis; the mean factor scores for each group differed, with the kwashiorkor groups furthest from the controls. Results of discriminant analysis using the amounts of different numbers of protein variables (3 to 24) were compared for posterior assignment of individuals to groups. The validity of the method was tested by analysis of plasma aliquots obtained from patients following initiation of therapy and which were not a part of the training set. Predictive performance (prognosis of patient survival) depended upon the number of protein variables used. Although artifactual fitting of the data is expected to contribute to performance as the number of variables is increased, use of as many as 7 variables may be justified, even with our small patient groups. Possible use of these results for development of a practical clinical test is discussed. PMID- 3089680 TI - Bleeding pattern, outcome of accidental pregnancies and levonorgestrel plasma levels associated with method failure in Norplant implants users. AB - The aim of this study was to characterize the bleeding pattern, the outcome of pregnancies and the levonorgestrel plasma levels associated with method failures in Norplant implants users. Nineteen pregnancies are reported in 458 woman and 21,589 woman-months observed during the first eight years of Norplant use. Pregnancy rates increased slightly during the first six years of use, attaining a Pearl Index above three thereafter. All women who became pregnant had experienced a regular bleeding pattern in the six months preceding conception. Levonorgestrel plasma levels observed at different intervals before conception and during the conceptional cycle were similar to those observed in non-pregnant women at comparable intervals after Norplant insertion. The nineteen pregnancies ended in thirteen term deliveries, one premature delivery, three abortions and two ectopic pregnancies. No abnormalities were found in the infants. The two ectopic pregnancies are the only ones reported for Norplant users in The Population Council studies. The overall incidence is less than 0.8 per 1000 woman-years. PMID- 3089681 TI - Levonorgestrel concentrations in maternal and infant serum during use of subdermal levonorgestrel contraceptive implants, Norplant, by nursing mothers. AB - The transfer of levonorgestrel to infants was studied in 42 lactating women in whom the contraceptive subdermal implants, Norplant, were inserted 30 to 40 days postpartum. The women breastfed their infants for one year. Simultaneous mother and infant blood samples were taken once during the year. The levonorgestrel serum concentrations were measured by radioimmunoassay. During the first postinsertion month, the levonorgestrel concentration in the infants serum amounted, on the average, to 5% of the maternal concentration. Thereafter, the ratio ranged from 8 to 13%. The implications of this finding are discussed. PMID- 3089682 TI - Contraceptive steroid concentrations in women with early active schistosomiasis: lack of effect of antischistosomal drugs. AB - Plasma concentrations of the oral contraceptive steroids (OCS) ethinyloestradiol (EE2) and levonorgestrel (LNG) have been determined in women with early active schistosomiasis and compared to those obtained in healthy volunteers. Steroid concentrations following a single dose of Ovral (500 micrograms LNG, 50 micrograms EE2) or during a multiple dose regimen were unaffected by the disease. There was no significant effect of the antischistosomal drugs praziquantel (40 mg X kg-1) or metrifonate (10 mg X kg-1 X 3 at 2-week intervals) on plasma steroid concentrations. In regular users of OCS, significantly higher concentrations of LNG were observed than in women who received only a single dose. We conclude that there is no pharmacokinetic reason for withholding OCS from patients with early active schistosomiasis who are also receiving either praziquantel or metrifonate. PMID- 3089684 TI - Classification and recall of pictures after unilateral frontal or temporal lobectomy. AB - Classification and recall of pictures of familiar objects were studied in 21 normal control subjects and 75 patients with unilateral cerebral excisions. The patients with frontal-lobe excisions were impaired at categorizing the pictures and at recalling the objects depicted. Left and right temporal-lobe groups performed the sorting task normally, but the left temporal-lobe groups were impaired at recalling picture names. The right temporal-lobe groups were unimpaired. A negative correlation between the number of items uncategorized and the number recalled was found in the right frontal-lobe group but not in the left, who were impaired also at recalling the items that they had classified correctly. It is concluded that impaired categorization played a major role in determining the recall deficits in the right frontal-lobe group but not in the left, whose impaired recall may also be due to defective retrieval. The poor recall of the left temporal-lobe groups is thought instead to depend on abnormally rapid forgetting. PMID- 3089683 TI - Pharmacokinetics of oral contraceptive steroids in Egyptian women: studies with Ovral, Nordette and Norminest. AB - Plasma concentration profiles and pharmacokinetic parameters have been obtained following single dose administration of three commonly used oral contraceptive steroid preparations, Ovral, Nordette and Norminest to Egyptian women. The constituents of the preparations are as follows: Ovral (50 micrograms ethinyloestradiol, EE2 and 500 micrograms levonorgestrel, LNG); Nordette (30 micrograms EE2 and 150 micrograms LNG); and Norminest (35 micrograms EE2 and 500 micrograms norethisterone, NOR). Peak plasma concentrations of EE2 ranged between 116-160 pg ml-1 for Ovral, 55-78 pg ml-1 for Norminest and 30-70 pg ml-1 for Nordette. There was no significant difference in half-life (t1/2), oral clearance (CL) or apparent volume of distribution (Vd). The relative values of the area under the plasma concentration-time curve (AUC) reflected well the different amounts of oestrogen in each preparation. There was no significant difference in t1/2, CL or Vd for LNG in the 2 preparations containing this progestogen. The mean AUC following Nordette (150 micrograms LNG) was 40% of that following Ovral (500 micrograms LNG; p less than 0.001). Comparing pharmacokinetic parameters for the same dose of LNG (Ovral) and NOR (Norminest) showed the AUC to be decreased and CL and Vd increased in the latter group. The study indicates that the kinetic profile of the OCS in healthy Egyptian women are similar to other ethnic populations. PMID- 3089685 TI - Idiotypic regulation of autoantibody production. AB - The manuscript will deal with various aspects of the origin of autoantibody formation in relationship with idiotypy. The proposed analysis will cover three major aspects: (1) overview of the published data on idiotypic characterization of autoantibodies in various systems by conventional serologic investigation; (2) presentation of the structural and genetic data available for autoantibodies; and (3) description of the most significant experiment of in vivo manipulation of autoantibody production using idiotypy as the central element for immune regulation. The manuscript will also discuss some theoretical aspects of regulation by idiotype and its possible relevance to improve our understanding of autoreactivity as well as the pathogenesis of certain autoimmune diseases. PMID- 3089686 TI - Long-term normoglycemia in pancreatectomized dogs transplanted with frozen/thawed pancreatic islets. AB - Storage of pancreatic islets by cryopreservation would greatly facilitate a large scale program of clinical islet transplantation. We report success on long-term follow-up with autotransplantation of frozen/thawed canine pancreatic fragments. Total pancreatectomy and islet isolation by collagenase ductal perfusion and mechanical disruption preceded either acute autotransplantation or cryogenic preservation prior to autotransplantation. Cryopreservation was by dimethylsulfoxide equilibration, cooling at 0.25 degrees C/min to -75 degrees C, storage in liquid N2 and thawing at 3.5 degrees C/min. Four of five acutely autotransplanted dogs remained normoglycemic for 20 months, with three of four maintaining normal K values on intravenous glucose tolerance test (IVGTT) and nondiabetic values on oral GTT. Four of four dogs transplanted with frozen/thawed islets remained normoglycemic for 15 months with three of four maintaining nondiabetic IV GTT K values and normal oral GTTs for 15 months. Both acutely transplanted and frozen/thawed islets are capable of maintaining long-term metabolic control. Cryopreservation preserved viability of sufficient canine pancreatic islets to reverse diabetes with autotransplantation. Function of the frozen-thawed islets showed minimal deterioration during a follow-up of 15 to 18 months. PMID- 3089688 TI - Clinical triads: water metabolism, the NPO patient, and parenteral nutrition. PMID- 3089687 TI - Tissue-plasminogen activator: a new drug in reperfusion therapy (continuing education credit). PMID- 3089689 TI - Interpreting arterial blood gas values. PMID- 3089690 TI - Fatty acid composition and arachidonic acid metabolism in vitreous lipids from canine and human eyes. AB - About 55% of the acyl groups of dog and human vitreous are unsaturated fatty acids. The major components are oleate (18:1, n-9) and arachidonate (20:4, n-6) with moderate amounts of linoleate (18:2, n-6) and docosahexaenoate (22:6, n-3). Palmitate (16:0) and stearate (18:0) are the major saturated fatty acids. There are no significant changes between ages 37-82 years in the fatty acyl group content and composition of human vitreous. In vitreous from Irish setters with hereditary rod-cone dysplasia (RCD) the levels of oleate are decreased with a concomitant increase in arachidonate. [1-14C]Arachidonic acid was actively incorporated into canine vitreous glycerolipids both in vitro and in vivo. The incorporation was mainly into phosphatidylinositol, triacylglycerol, phosphatidylcholine and phosphatidylethanolamine. There were some differences in the pattern of incorporation between human and dog and between in vivo and in vitro incubations of canine vitreous. Glycerolipid acylation was significantly increased in phosphatidylinositol and phosphatidylcholine in RCD canine vitreous. The pattern of incorporation of [U-14C]docosahexaenoic acid into vitreous glycerolipids was different from arachidonic acid incorporation. Although vitreous did not produce any measurable enzymatic synthesis of cyclooxygenase and lipoxygenase products from [1-14C]-arachidonic acid in vitro, there was significant generation of autooxidation products. These results suggest an active lipid metabolism in vitreous. PMID- 3089691 TI - Inhibition of nocturnal gastric secretion by trimoprostil, a synthetic prostanoid. AB - Eleven healthy volunteers had nocturnal gastric secretion studied on three occasions to compare, in a randomized manner, the gastric inhibitory effects of two doses (1.5 and 3.0 mg) of trimoprostil with placebo. Nocturnal gastric secretion of acid was significantly inhibited for 7 hours with the higher dose of the drug, by a total of about 50 percent. The output of pepsin was also reduced, albeit not as markedly as acid, for the first 5 hours of the study. It is concluded that trimoprostil, in the doses used in the present study, is capable of reducing gastric secretion without producing side-effects. PMID- 3089693 TI - Evolution of immunologically important genes in the genus Mus. PMID- 3089692 TI - Practical considerations in the nutritional management of the cancer patient. PMID- 3089695 TI - Igk polymorphism in M. musculus domesticus populations from Maryland and Delaware. PMID- 3089694 TI - Polymorphism and evolution of Igh-V gene families. PMID- 3089696 TI - Evidence that wild mice (Mus musculus musculus) express lambda genes that differ from those in BALB/c. PMID- 3089697 TI - A comparative analysis of the anti-phosphorylcholine response of CLA and BALB/c mice. PMID- 3089698 TI - Genetic features of major geographical isolates of Mus musculus. PMID- 3089699 TI - New species of messenger RNA in aflatoxin B1 induced hepatocellular carcinoma. AB - Differences in the mRNA species were observed when cDNA complementary to HnRNA from normal liver was hybridized with mRNA from hepatocellular carcinoma induced by aflatoxin B1. The hybridizations between cDNA complementary to HnRNA from liver cell carcinoma and HnRNA from normal liver indicate that there is homology between their sequences. The findings in this paper suggest that mRNA species normally restricted to the cell nucleus are present in the cytoplasm of liver carcinoma cells. PMID- 3089700 TI - Tuberculosis in Korea. The relationship between prior therapy and drug resistance. AB - A review of 121 culture-positive cases of pulmonary tuberculosis from 1979 to 1984, including both Korean and American patients, at the major US military hospital in Korea indicated that most antituberculosis drug resistance occurred in patients with a history of previous antituberculosis therapy. The 98 patients without previous therapy who were not household contacts of a known resistant case had low rates of drug resistance (7 percent to isoniazid, 5 percent to streptomycin, 2 percent to p-aminosalicylic acid, and none to rifampin or ethambutol). All were sensitive to at least two of the drugs in the commonly prescribed regimen of isoniazid, rifampin, and ethambutol. In contrast, both patients who were household contacts of a known resistant case and 11 (52 percent) of the 21 patients with previous therapy had drug-resistant organisms. Our data support the use of isoniazid as preventive therapy for those who develop tuberculin reactivity while in Korea, in the absence of close contact with a known resistant case. Our data also suggest that the regimen of isoniazid, rifampin, and ethambutol is appropriate initial therapy for active disease acquired in Korea, provided that an adequate history excluding these risk factors can be obtained. PMID- 3089701 TI - Cigarette smoking divided by professional groups in Beijing. PMID- 3089702 TI - Rheohepatogram as a parameter in assessing immediate effects of propranolol on portal hypertension. PMID- 3089703 TI - Osteoarthritis in bipedal rats. PMID- 3089704 TI - Traumatic subdural hygroma. Report of 7 cases in children. PMID- 3089705 TI - Animal model of suppurative cholangitis and bilirubin cholangiolithiasis. PMID- 3089706 TI - Regeneration of full-layer necrosed skull after high-tension electrical injury. PMID- 3089707 TI - Human colonic cancer associated antigens detected by three monoclonal antibodies. PMID- 3089708 TI - Human urine gas change measurement and its application in acute renal failure. PMID- 3089709 TI - An epidemiological study on mental retardation among children in Chang-qiao area of Beijing. PMID- 3089710 TI - Interaction and regulation of macrophage receptors. AB - Macrophages express distinct plasma membrane receptors for different isotypes of immunoglobulin, bear at least two receptors for cleaved third complement component (CR1 and CR3) and have a lectin-like receptor that mediates endocytosis of glycoproteins or glycoconjugates with terminal mannose or fucose residues (MFR). Interferon-gamma, a macrophage-activating factor, induces effects common to other interferons as well as having unique effects on cell function. The down regulation of MFR, induction of IgG2a Fc receptors and Class II antigens and enhanced production of superoxide and hydrogen peroxide can be considered interferon-gamma-specific effects on macrophages. Previous reports described synergism of various interferon preparations in anticellular and antiviral effects. However, interferon-alpha/beta can selectively antagonize the down regulation of macrophage MFR by interferon-gamma. The macrophage MFR and CR3 also play a synergistic role in the uptake of zymosan and Leishmania donovani in the absence of serum. The receptors may act independently or in concert. Cleaved third complement components can be specifically eluted from zymosan particles in the absence of exogenous complement and are derived from the macrophages themselves. These studies indicate a role for macrophage complement in local opsonization of pathogens at extravascular sites and focus on the role of the tissue macrophage in first-line host defence. PMID- 3089711 TI - Bacterial lipopolysaccharides modify signal transduction in the arachidonic acid cascade in macrophages. AB - Macrophages are a potent source of arachidonic acid (20:4) metabolites. When macrophages interact with an appropriate stimulus, phospholipase activity is induced, resulting in the liberation of 20:4 from the membrane phospholipid and its quantitative oxygenation via either the lipoxygenase or cyclooxygenase pathways. We have attempted to dissect the molecular events coupling the initial membrane-perturbing signal to the phospholipase activity. Using a variety of stimuli and uncoupling agents we have found that receptor-mediated 20:4 release is triggered by a series of sequential signals, including ligand-receptor binding, receptor clustering, Na+-dependent events, the synthesis of a rapidly turning over protein and finally an influx of Ca2+ into the cell. Bacterial lipopolysaccharides (LPS) are poor triggers of the 20:4 cascade. However, pretreatment of cells with LPS leads to the establishment of a 'primed' or 'intermediate' state which can act synergistically with subsequent signals. Hence, the amount of 20:4 metabolites secreted in response to a variety of triggers is increased 3-10-fold in LPS-primed cells, and the lag phase usually observed in 20:4 secretion disappears. The observations presented suggest a two stage mode of signalling in the receptor-mediated induction of the 20:4 cascade. PMID- 3089712 TI - Secretion of toxic oxygen products by macrophages: regulatory cytokines and their effects on the oxidase. AB - We are attempting to identify cytokines that regulate macrophage secretion of reactive oxygen intermediates (ROI) and to analyse the biochemical basis of their effects. In both humans and mice, interferon-gamma (IFN-gamma) appears to be the chief factor secreted by clonally unselected lymphocytes that enhances macrophage oxidative metabolism and antiprotozoal activity. In vivo administration of recombinant IFN-gamma enhances the ROI secretory capacity of monocytes in humans, and the secretion of ROI and killing of protozoa by peritoneal macrophages in mice. A protein secreted by murine tumours and certain non-malignant cells exerts opposing effects. This macrophage deactivation factor (MDF) both blocks the induction of activation by IFN-gamma and reverses pre-existent activation. MDF action is non-toxic and selective, suppressing the secretion of ROI, killing of intracellular protozoa, and expression of Ia antigen, without inhibiting secretion of several other products, or synthesis of protein, ingestion of particles or adherence to culture vessels. The suppressive effect of MDF is reversed over several days after its removal. This reversal is hastened by IFN gamma. Profound suppression of oxidative metabolism accompanies the differentiation of murine monocytes into Kupffer cells. The capacity of Kupffer cells to secrete ROI and kill intracellular protozoa remains deficient even after exposure to IFN-gamma. Thus, four states of macrophage activation can provisionally be discerned: the transition of mouse peritoneal macrophages from the non-activated to the activated state is accompanied by a ninefold increase in affinity of the superoxide-producing enzyme for NADPH, without a marked increase in cellular Vmax or content of cytochrome b559. The MDF-induced transition of mouse peritoneal macrophages from the activated to the deactivated state is accompanied by both an increase in Km and a decrease in apparent V max of the oxidase. There are no changes in the phorbol myristate acetate receptor number or affinity, glucose transport, NADPH levels, cytochrome b559 content, catalase (EC 1.11.1.6) GSH, GSH peroxidase (EC 1.11.1.9), GSH reductase (EC 1.6.4.2) or myeloperoxidase, consistent with the suppressed ROI secretory capacity and antiprotozoal activity of these cells. The Kupffer cell, whose non-responsiveness to IFN-gamma may mark it as inactivated, appears to lack detectable NADPH oxidase activity, despite the probable presence of cytochrome b559, and in this regard differs from both non-activated and deactivated macrophages.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3089713 TI - Macrophage antigens and the effect of a macrophage activating factor, interferon gamma. AB - Molecules characteristic of mononuclear phagocytes have been identified using monoclonal antibodies (MAb). MAb 3.9 reacts with a 150/95 000 dalton heterodimer which is found exclusively on monocytes and macrophages and appears to be the third member of the lymphocyte function-associated (LFA) family of molecules. In contrast, the reactivity of MAb 24, which bonds to a 175 000 dalton protein, is most highly expressed on the macrophages in lymphoid tissue. Both 3.9 and 24 detect the interdigitating cells in the T cell areas of these tissues, which strongly suggests that this cell type belongs to the macrophage family. A third MAb, 10.1, reacts selectively with a set of macrophages outside lymphoid tissue, particularly on Kupffer cells, alveolar macrophages and microglia. Thus subsets of tissue macrophages are proving easy to identify whereas it appears that circulating monocytes are not easily subdivided. None of the MAbs detected either Langerhans' cells, dendritic reticulum cells of B cell areas, or osteoclasts, indicating that these cells are not mononuclear phagocytes. As a first step towards identifying macrophage molecules which have a biological function, we have investigated the effect of macrophage-activating factor, interferon-gamma, on the expression of macrophage membrane molecules. There was greatly increased expression of only two out of ten molecules detected with anti-myeloid antibodies. PMID- 3089714 TI - Three-dimensional analyses of the binding of synthetic chemotactic and opioid peptides in the Mcg light chain dimer. AB - Synthetic peptides with chemotactic or opioid activity were bound to crystals of a light chain dimer and their three-dimensional structures and modes of binding were determined by X-ray analysis. The chemotactic series consisted of di- and tripeptides initiated with N-formylmethionine or N-formylnorleucine residues. Opioid peptides included the enkephalins and casomorphins ranging in length from four to seven residues. The binding region of the protein proved to be malleable in adjusting to the surface contours of the peptides. Aromatic contact residues, as well as polypeptide segments of hypervariable loops, moved to improve the complementarity with the ligands. The peptides were even more flexible and tended to conform fairly closely to the space and geometry available for occupancy in the binding sites. Binding interactions were not confined to the interior of the cavity. In both the chemotactic and opioid series, the carboxyl tails of the peptides encroached upon the outer surfaces of the rim and contributed to the binding energies for the protein-ligand complexes. The peptide bond in N formylmethionyltryptophan was found to be in the energetically unfavourable cis configuration. There was also evidence for less severe distortions in peptide bond geometry when N-formyltripeptides were bound to the dimer. PMID- 3089715 TI - [Ultrastructural changes of anterior chamber angle tissues in primary open-angle glaucoma]. PMID- 3089716 TI - [A China-made non-contact tonometer--clinical trial]. PMID- 3089717 TI - [A calibrated applanation tonometer]. PMID- 3089718 TI - [Relation between the depth of the anterior chamber and anterior chamber angle in primary angle closure glaucoma]. PMID- 3089719 TI - [Phacolytic glaucoma]. PMID- 3089720 TI - [Axial length and myopia]. PMID- 3089721 TI - [Effect of smoking on the anterior segment of the eye]. PMID- 3089722 TI - [Nasolacrimal duct trephination in treating chronic dacryocystitis]. PMID- 3089723 TI - [Scanning electron microscopy of normal lens fibers of the rat]. PMID- 3089724 TI - [Epidemiologic study of vernal keratoconjunctivitis in the northwest region of China]. PMID- 3089725 TI - [Clinical application of the pneumo-tonometer]. PMID- 3089726 TI - [Evaluation of the physiologically based treatment of amblyopia]. PMID- 3089728 TI - [Determination of hydroxyproline and hexosamine in the rabbit cornea]. PMID- 3089727 TI - [Preparation of long-acting rifampin film for the treatment of trachoma]. PMID- 3089729 TI - [Localized acid mucopolysaccharidosis of the cornea--a histochemical and ultrastructural study]. PMID- 3089730 TI - [Corneal graft endothelium in penetrating keratoplasy]. PMID- 3089731 TI - [Corneal endothelium]. PMID- 3089732 TI - [Analysis of factors affecting the endothelium of clear corneal transplants]. PMID- 3089733 TI - [Large grafts for penetrating keratoplasty--clinical analysis of 48 cases]. PMID- 3089735 TI - [Anterior chamber depth measurement in the early diagnosis of primary angle closure glaucoma]. PMID- 3089734 TI - [Keratoplasty for infectious corneal ulcers--analysis of 110 cases]. PMID- 3089736 TI - [Depth of the anterior chamber in normal eyes and eyes with primary glaucoma]. PMID- 3089737 TI - [Deprivation amblyopia]. PMID- 3089738 TI - Histopathologic analysis of the so-called secondary blastic non-Hodgkin's malignant lymphomas. AB - Fifteen cases of blastic transformation of originally low grade malignant lymphomas to high grade malignant ones were studied. The material was selected from the biopsy registry of our institute and had been collected over the period of 1 January 1982 to 1 March 1984. In 10 cases this transformation was verified morphologically (in 8 cases by successive biopsies, in 2 cases in the sectional material). At the time of the first biopsy, transformation was suspected in four cases. There were 4 cases of transformation of centroblastic-centrocytic lymphomas to centroblastomas, one case of centrocytoma transformed to centroblastoma, two cases of immunocytomas transformed to centroblastomas, and three cases of immunocytomas transformed to immunoblastomas. The transformation took place within a mean time of 9.5 months after the first biopsy, and 6 patients died, on the average, within 5.3 months after the rebiopsy. In live cases only 1 bioptic examination was done on the basis of which the blastic transformation has been suspected, though not proved yet. There was one case of a suspected transformation of a centroblastic-centrocytic lymphoma to a centroblastoma type with structural remnants of low grade malignant lymphomas, in one case the In the further two cases there were blastic malignant lymphomas of the centroblastoma type with structural remnants of low grade malignant hymphomas, in one case the centroblastic-centrocytic type, in the other the immunocytic lymphoma type. The morphological criterion for a suspected rise of a secondary blastic lymphoma is the presence of clear regions composed of an accumulation of blasts with increased mitotic activity in the prevalent structure of the low grade malignant lymphoma. PMID- 3089739 TI - Evidence of Chlamydia trachomatis infection in gynaecological patients. AB - Direct microscopic examination of cervical smears taken from gynaecological patients and stained by Giemsa and Gimenez revealed the presence of chlamydial inclusions in 2 and elementary bodies in 6 out of 40 samples tested. Attempts of demonstration of chlamydiae from cervical smears of further patients in chick embryo yolk sacs and cycloheximide-treated McCoy cells using the centrifugation of infectious inocula succeeded in 4 and 9 cases of 71 patients examined, respectively. One isolated strain behaved as Chlamydia trachomatis based on its sensitivity to sulfadiazine, absence of killing the intraperitoneally inoculated mice, demonstration of its inclusions by iodine staining and by detection of its elementary bodies by immunofluorescence technique using mouse serum directed to C. trachomatis but not C. psittaci serotypes. At the same time, 11 of 68 patient sera tested by microimmunofluorescence test contained IgG antibodies to genitourinary serotypes of C. trachomatis, suggesting the previous contact of patients with sexually-transmitted chlamydiae. The results obtained indicate that chlamydiae may pose a public health problem in women of sexually active age also in Czechoslovakia. PMID- 3089740 TI - Endoscopic papilosphincterotomy. AB - Author describes own experience with endoscopic papilosphincterotomy which performed in 29 patients as the first in Czechoslovakia. He succeeded in 29 out of 33 patients, i.e. in 87.9% of cases. Endoscopic papilosphincterotomy was indicated in 24 patients (82.6%) with choledocholithiasis and in 5 patients with benign stenosis of papilla of Vater. In all patients with choledocholithiasis the removal of concretions from biliary passages was successful: in 8 cases (33.3%) they were spontaneously released, in remaining 16 cases (66.7%) they were extracted using the Dormia's basket. In the group of 29 patients, in 2 cases (7.8%) was observed cholangitis which was cured by combined treatment with antibiotics and antispasmodics. Urgent surgery was not necessary in any case. PMID- 3089741 TI - Fat globulemia in early diagnostics of traumatic fat embolism. AB - In our opinion, this clinical study demonstrates the intravascular formation of globules, macroglobules and their aggregations both in the association with the type of general anaesthesia and with the operative osteosynthesis of long bones. Within the framework of this study changes in the level of lactic acid in blood serum and of total ketosubstances in blood were followed as well as the levels of total lipids, triglycerides, phospholipides, serum lipase, non-esterified and esterified fatty acids, changes in blood coagulation and 17-ketosteroides in blood. The observed changes supported the opinion that the development of fat globulemia was associated with humoral and physicochemical changes in blood. Repeated evaluations of fat globulemia in plasma are important for studies on pathogenesis and development of fat embolism. In practice, they help: to diagnose especially subclinical forms of fat embolism with non-marked clinical symptoms; to define a suitable term of both primary and delayed operation performed in the period of ending katabolic phase after severe trauma; to define an optimum time for the indication of osteosynthesis to the end of manifest fat embolism; to control positive effects of drugs used for the prophylaction and treatment of fat embolism. In this way it is possible to objective the effectiveness of a rational prophylaxis and treatment of fat embolism. Following factors contribute to macroglobulamia and to manifestation of F. E.: injuries to bones, tissues and organs; stress, posttraumatic shock; severe hemorrhagic hypotension; posttraumatic hypercoagulation with possible binding to the development of a consumption coagulopathy; heavy changes of acid-base balance; increase of catecholamines in plasma; hormonal and general metabolic disturbances; posttraumatic dyslipidemia with special regard to the decrease of beta lipoproteins and of lipoproteinlipase activity together with the increase of lipoproteins having a very low density and with the occurrence of a significant lipoprotein coalescence. The prospective study on the globulemia changes is based on the following examinations: in 76 injured patients: a short time observation (24 hours) of the globulemia changer after osteosyntheses in general anesthesia. The operative interventions were usually performed 6 to 8 days after injury. in 60 injured patients with fractures (single or multiple fractures, fractures in polytrauma patients): a long-time observation (28 days) of the globulemia changes. PMID- 3089742 TI - Flow cytometric estimation of cell cycle parameters using a monoclonal antibody to bromodeoxyuridine. AB - An estimation of cell kinetic parameters was made by simultaneous flow cytometric measurements of DNA and bromodeoxyuridine (BrdUrd) contents of cells. The procedure described in this paper involves the incorporation of BrdUrd by S phase cells, labeling the BrdUrd with an indirect immunofluorescent technique using a monoclonal anti-BrdUrd antibody, and staining DNA with propidium iodide (PI). The amount of incorporated BrdUrd in HeLa cells was proportional to that of synthesized DNA through S phase. For all cell lines examined, the pattern of BrdUrd incorporation was essentially the same and the rate of DNA synthesis during S phase was not constant. The bivariate BrdUrd/DNA distributions showed a horse-shoe pattern, maximum in the mid S phase and minimum in the early and late S phases. Furthermore, the durations of cell cycle (Tc) and S phase (Ts) were estimated from a FLSm (fraction of labeled cells in mid S phase) curve that was generated by plotting the percentage of BrdUrd pulse-labeled cells in a narrow window defined in the mid S phase of the DNA histogram. The values of these parameters in NIH 3T3, HeLa S3, and HL-60 cells were in good accordance with the reported data. This FCM method using the monoclonal anti-BrdUrd antibody allows rapid determination of both cell cycle compartments and also Ts and Tc without the use of radioactive DNA precursors. PMID- 3089743 TI - Indium-111-labeled autologous leukocyte scanning in gastrointestinal graft versus host disease (GVHD). AB - The technique of scanning with indium-111 autologous leukocytes has been used to assess gastrointestinal graft-versus-host disease (GVHD) following allogenic marrow transplantation. In patients with active disease, abdominal scans showed extensive abnormal localization in the bowel, while in those whose disease was quiescent after responding to treatment, scans showed localized ileocecal involvement. Rectal histology showed excellent agreement with scanning in the diagnosis of GVHD, but in three of six cases with active disease underestimated disease severity. Indium-111 leukocyte scanning is a useful noninvasive technique for the diagnosis and assessment of gut GVHD. PMID- 3089745 TI - Screening of colorectal cancer. AB - Colorectal cancer (CRC) remains a cancer in a disappointing location. However, its location clearly has an advantage that could theoretically permit efficient secondary prevention: the preceding of the cancer by a benign lesion, ie, the adenoma. Complete colonoscopy and its substitute, the double-contrast barium enema, and their specific limitations, must be reserved for high-risk patients: hereditary cancers and ulcerative colitis. For all the others, ie, adults of 45 years of age and with standard risks, the proposal is either to select the patients to be colonoscoped through occult blood testing of the stools or to perform a fiber sigmoidoscopy or a combination of both. Although imperfect, both methods allow the detection of polyps and cancers at a presymptomatic stage, when they are either benign or malignant, but localized and with a better prognosis. However, the absolute proof of the benefits of this strategy of screening would be the demonstration by controlled studies of a prolonged survival rate or a decrease in morbidity. Until now, this proof is not fully available. PMID- 3089746 TI - Malnutrition in patients with gastrointestinal malignancy. Significance and management. AB - Malnutrition is a common accompaniment of gastrointestinal malignancy. The etiology of such malnutrition is multifactorial, but, when present, is a poor prognostic sign. Simple causes of decreased intake such as obstruction are readily overcome by distal enteral or parenteral feeding. Metabolic abnormalities that limit the efficacy of parenteral nutrition in such patients have been identified and, although not uniform, give further insight into the manner in which the host and the tumor partition energy and substrate. Widespread use of adjunctive parenteral nutrition in patients undergoing chemotherapy or radiation therapy for gastrointestinal malignancy has not improved tolerance or efficacy of such treatment. Nutritional support of the malnourished patient with a gastrointestinal cancer, prior to a major operation, has been shown to decrease perioperative morbidity and mortality. PMID- 3089747 TI - Cost efficacy of routine screening for diabetes in pregnancy: 1-h versus 2-h specimen. AB - Undetected gestational diabetes mellitus (GDM) is associated with a two- to fivefold increase in perinatal morbidity and mortality. Widespread screening of the obstetric population (resulting in identification and treatment) should reduce these rates. Seven hundred ninety-eight women were examined during a 13-mo period of universal glucose challenge testing (GCT). A total of 2.8% of the population had an abnormal oral glucose tolerance test (OGTT). Thirty percent of those with an abnormal OGTT were less than 25 yr old. The specificity of a 1-h GCT (50-g carbohydrate load) using a threshold of either 140 or 150 mg/dl was compared with that of a 2-h specimen using a threshold of 118 mg/dl to determine whether the cost of screening could be reduced. One- and 2-h specimens were obtained in 347 of these women. A 34% reduction in the number of follow-up OGTTs required would have been achieved if a 2-h specimen had been used as the index instead of a 1-h specimen (P less than .05). As a result, the (direct and indirect) cost per patient identified with GDM would have declined 23.5%--from $866 to $662. No comment concerning the actual false-negative rate of either the 1- or 2-h GCT can be made because only select women underwent an OGTT. To assess the validity of the 2-h threshold, an OGTT was performed in an additional 190 women if either the 1- or 2-h screen was abnormal. The results were confirmatory: the 2-h screen would have reduced the cost per case identified by 32% in this small group. Screening on the basis of past medical history clearly lacked sensitivity and cost efficacy in comparison with the GCT and should be abandoned as a practice. PMID- 3089744 TI - Effect of dietary fat and residues on fecal loss of sterols and on their microbial degradation in cystic fibrosis. AB - Although various etiologic factors have been implicated, the mechanism responsible for bile acid malabsorption in CF remains unknown. Eight CF children studied twice on a normal diet supplemented with pancreatic enzymes and once during a one-month period of Vivonex administered by continuous nasogastric infusion were compared to age-matched controls. On the fat and residue-free elemental diet, there was a modest decrease in steatorrhea and no change in the daily excretion of nitrogen and neutral sterols. However, normalization of bile acid output (485.6 +/- 65.0 to 160.6 +/- 29.2 mg/24 hr) to control levels (150.2 +/- 60.7) was noted. Diminished microbial degradation of both neutral and acidic sterols and a smaller amount of bile acids adsorbed to decreased residues were also found. The data do not support the possibility of a bile acid ileal transport defect and suggest that the most important single factor responsible for the intraluminal sequestration of bile acids in CF is dietary residues. Because of significant ongoing losses of nitrogen and lipids, pancreatic enzymes should be given to CF patients on elemental diets. PMID- 3089748 TI - [Genetic etiology of esophageal cancer--III. The spontaneous and mitomycin-C (MMC) induced sister chromatid exchanges (SCE) and chromosome aberrations in cultured lymphocytes from members of "high risk" and "low risk" esophageal cancer families in Linxian County]. AB - The spontaneous and mitomycin-c (MMC) induced sister chromatid exchanges (SCE) and chromosome aberrations in cultured lymphocytes from members of "high risk" and "low risk" esophageal cancer families in Linxian County were studied. The results showed that the frequencies of the spontaneous SCE of "high risk" and "low risk" esophageal cancer groups were 7.8 +/- 0.25 and 8.3 +/- 0.25/per cell. There were no difference between these two groups (P greater than 0.5). The frequencies of the SCE induced by MMC in "high risk" and "low risk" esophageal cancer groups were 43.8 +/- 2.4 and 21.6 +/- 1.1/per cell. There were noteworthy difference (P less than 0.001). However, the frequencies of the spontaneous and MMC induced chromosome aberrations in "high risk" cancer families were higher than those of the "low risk" ones. PMID- 3089749 TI - [Amino acid sequence of guanyl-specific ribonuclease from Penicillium chrysogenum 152A]. PMID- 3089750 TI - [The use of liposomes in the transformation of Streptomyces griseus protoplasts]. PMID- 3089751 TI - [Selective induction of mutations during the early stage of Drosophila spermatogenesis after treatment with 1,2-dichloroethane]. PMID- 3089752 TI - Phase I trials of biological response modifiers. AB - An analysis of recently conducted phase I trials of biological response modifiers (BRM), performed mainly under the sponsorship of the BRM Program of the National Cancer Institute, has led to the development of a format for performing such trials with these agents in the future. The evolution of this format and its use in ongoing phase I trials of recombinant beta and gamma interferons is discussed. An evaluation of the method will be undertaken at the conclusion of these studies. PMID- 3089753 TI - [TRH-stimulated growth hormone secretion in acromegaly. Therapeutic results with 188 patients]. AB - TRH-induced stimulation of hGH secretion before and after operation or radiotherapy and during bromocriptine treatment was tested in 188 patients with acromegaly. A normal hGH level (basal level less than 5 ng/ml) was achieved after operation in 106 patients (58%). Postoperatively persisting elevated hGH levels were reduced to normal by bromocriptine in 39%, by radiation in 22% and by combined radiation and bromocriptine in 48%. In cases with additional hyperprolactinaemia a response to bromocriptine occurred in 47%. Pre- and postoperative TRH-induced stimulation of hGH secretion was not correlated with the rate of either normalization nor recurrence and thus has no prognostic significance. PMID- 3089754 TI - [Cardiogenic shock. Therapy]. PMID- 3089755 TI - Nutritional implication of schistosomiasis. PMID- 3089756 TI - Preliminary clinical trial of oral oxamniquine in the treatment of Schistosoma mansoni in children in Ethiopia. PMID- 3089757 TI - Plasma catecholamines following nursing procedures in a neonatal ward. AB - Plasma catecholamines (CA) were determined in arterial blood from infants in a neonatal ward before and after various management procedures. Special care led to a 60% increase in plasma noradrenaline levels (P less than 0.02) whereas the adrenaline concentrations were not significantly affected. CA levels tended to be slightly higher after heel prick and gavage feeding than before, but the differences were not significant. PMID- 3089758 TI - A striking sex difference in the gonadotropin response to gonadectomy during infantile development in the rhesus monkey (Macaca mulatta). AB - The present study was conducted to examine further the view that the early postnatal ontogeny of the neuroendocrine control system that regulates ovarian function in the rhesus monkey differs from that which governs testicular activity in this species. To this end, time courses of gonadotropin secretion were determined from birth until 40 weeks of age in neonatally ovariectomized (n = 6) and gonad-intact (n = 4) female rhesus monkeys by monitoring circulating LH and FSH concentrations in blood samples collected at weekly intervals. The developmental patterns of FSH and LH secretion in agonadal infantile females were then compared to those in a group of neonatally orchidectomized animals (n = 4). In addition, moment to moment changes in circulating LH concentrations were determined in agonadal male (n = 2) and female infants (n = 6) at approximately 1 month of age by collecting sequential blood samples every 10-20 min for 5-8 h. Ovariectomy at 1 week of age elicited a truncated and abbreviated rise in circulating LH concentrations, which contrasted to a postcastration LH hypersecretion of substantial magnitude and duration in males. The initial FSH response to neonatal ovariectomy and orchidectomy were similar, with both males and females exhibiting a striking and progressive rise in circulating levels of this gonadotropin during the immediate weeks following castration. Thereafter, however, a dramatic sex difference in the time course of open loop FSH secretion emerged; in males, plasma FSH concentrations declined to undetectable levels by 24 weeks of age, while in females, plasma concentrations of this gonadotropin were sustained at elevated levels for the duration of the 40-week period of observation. As a result of the foregoing sex difference in the early postnatal ontogeny of open loop gonadotropin secretion, circulating FSH to LH ratios in ovariectomized infantile female monkeys (2.3:8.1) were consistently greater than those in agonadal males (0.5:3.8). Interestingly, the elevated FSH to LH ratios in castrated females were associated with a relatively slow LH pulse frequency of approximately one pulse every 3-4 h. The expected circhoral frequency of pulsatile LH release was observed in agonadal males of comparable age. The persistence of sex differences in gonadotropin secretion in infantile rhesus monkeys several weeks after removal of the gonads suggests that the origin of these differences must reside at the hypothalamic-pituitary level rather than at the level of the gonad.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3089759 TI - Morphometric studies of rat anterior pituitary cells after gonadectomy: correlation of changes in gonadotropes with the serum levels of gonadotropins. AB - Anterior pituitary cells were studied with immunocytochemical methods 1-6 months after gonadectomy in male and female rats. One month after surgery, stained gonadotropes contained small scattered cisternae of rough endoplasmic reticulum, while others showed larger cisternae. The signet ring cells were observed 3 months after gonadectomy, and their numbers increased markedly by 6 months. Counts of freshly dispersed stained cells showed that in intact rats, the only significant sex differences were seen in the percentages of FSH and PRL cells. The females had higher percentages of both cell types. One month after castration, there were 2- and 3-fold increases in the percentages of LH and FSH cells, respectively. In females, ovariectomy resulted in a 2-fold increase in the percentage of LH cells and a slight but not significant increase in that of FSH cells. Three months after surgery, the percentages of LH or FSH gonadotropes increased from 8-12% to about 30% in both sexes. In the 6-month group, the percentages of stained gonadotropes were decreased to about 20% in both males and females. Counts of other pituitary cell types showed that the percentage of PRL cells in females declined to levels similar to those in the male within 1 month after ovariectomy. There was also a significant increase in the percentage of GH cells 1-3 months after ovariectomy. In contrast, the percentages of GH-producing cells decreased in the castrated males 3-6 months after surgery. The other pituitary cell types (ACTH and TSH) did not show significant changes after gonadectomy in either sex. The average area of gonadotropes was increased gradually, reaching a maximum 3 months after gonadectomy, after which it was decreased in the 6-month group. After ovariectomy, serum levels of gonadotropins correlated well with changes in areas of gonadotropes, showing a continuous increase until the third month, followed by a decrease after 6 months. Serum LH levels increased and then decreased after castration following the same pattern as that of the average areas. However, serum FSH levels continued to increase gradually throughout the entire 6 months. These studies are the first to quantify changes in all six pituitary cell types after gonadectomy. The counts confirm qualitative data reported previously that show changes in GH and PRL cells after gonadectomy (including sex differences). We extend previous studies that show that the expansion in gonadotropic cell area is correlated with a rise in both serum LH and FSH. PMID- 3089761 TI - Inhibition by hydrocortisone of prostacyclin synthesis by rat aorta and its reversal with RU486. AB - A rat aortic explant culture system was developed for the investigation of the effects of hydrocortisone (HC) and the glucocorticoid antagonist, RU486, on prostacyclin (PGI2 synthesis. HC, but not aldosterone, progesterone, 17 beta estradiol, or testosterone, inhibited spontaneous, epinephrine-stimulated and U46619 (an analog of thromboxane A2)-stimulated PGI2 synthesis by cultured aortic explants in a concentration- and time-dependent manner. Adequate inhibition of aortic explant PGI2 synthesis by physiological concentrations of HC was achieved after an 18-h culture. An 18-h time course was employed in subsequent experiments. In contrast, HC had no effect on arachidonic acid-stimulated PGI2 synthesis. Protein synthesis inhibitors, actinomycin D and cycloheximide, had no effect on the inhibitory action of HC on epinephrine- and U46619-induced release of PGI2. They exerted a direct inhibitory effect on aortic PGI2 synthesis. Arachidonic acid stimulated PGI2 release by the explants and was unaffected either by HC or by treatment with cycloheximide or actinomycin D. RU486 blocked the inhibitory action of HC on aortic PGI2 synthesis in a dose-dependent manner. Thus, the inhibitory effect of HC on vascular PGI2 synthesis is probably mediated through an inhibition of phospholipase A2 and not cyclooxygenase or other PGI2 synthase systems; furthermore, this inhibitory effect is not dependent upon de novo protein synthesis. RU486 antagonizes the inhibitory effect of HC. The inhibition of vascular PGI2 by hydrocortisone has implications in the pathogenesis of steroid-related hypertension and atherosclerosis and the antiinflammatory effect of steroids. PMID- 3089760 TI - RU486 antagonizes the inhibitory action of progesterone on prostacyclin and thromboxane A2 synthesis in cultured rat myometrial explants. AB - A myometrial explant culture system was developed to investigate the effect of progesterone and the antiprogestagen RU486 on prostacyclin (PGI2) and thromboxane A2 (TXA2) synthesis by the rat myometrium. After culture, eicosanoid synthesis was stimulated with arachidonic acid (AA) and the calcium ionophore A23187 (A23187). Spontaneous release of eicosanoids was also studied. Progesterone inhibited the spontaneous release of PGI2 and TXA2 release by myometrial explants in a concentration- and time-dependent manner. Adequate inhibition of myometrial eicosanoid synthesis by physiological concentrations was achieved at 18 h of culture: all subsequent studies were carried out after an 18-h culture of explants. A23187- and AA-stimulated PGI2 and TXA2 synthesis were inhibited equipotently by progesterone. 17 beta-Estradiol alone was without effect on spontaneous AA- or A23187-stimulated PGI2 or TXA2 synthesis and was without effect on progesterone-elicited inhibition of eicosanoid synthesis in the myometrial explants. The protein synthesis inhibitors, actinomycin D and cycloheximide, did not block the inhibitory action of progesterone on A23187- or AA-stimulated eicosanoid synthesis by the myometrial explants and alone mimicked the inhibitory action of progesterone. The inhibitory action of progesterone on AA- and A23187-stimulated PGI2 and TXA2 synthesis was antagonized in a concentration-dependent manner by RU486. These data indicate that within this ex vivo system, progesterone probably inhibits myometrial cycloxygenase, that progesterone may exert this action through inhibition of a modulating or permissive protein, and that the antiprogestagen RU486 is an effective in vitro antagonist or progesterone. PMID- 3089762 TI - In vivo and in vitro stimulatory effect of a gonadotropin-releasing hormone analog (HOE 766) on spermatogonial multiplication in the frog, Rana esculenta. AB - The effects of a GnRH analog (GnRHA), D-Ser-t-Bu6,desGly-NH2(10) (HOE 766) on spermatogenesis were analyzed in the frog, Rana esculenta. Intact animals caught at two different periods of the year (January and March) were treated with HOE 766 (GnRHA, 45 ng/g BW) at low (4 +/- 1 C) and high (22 +/- 2 C) temperatures. Hypophysectomized frogs were used also and, in addition to GnRHA, these animals were treated with crude pars distalis homogenate. In vitro incubations were carried out at 15 C, for 0, 6, and 24 h with the addition of 1 microgram GnRHA. Half of each testis was used as the untreated control. Histological sections of the testes were analyzed for the evaluation of the mitotic index of the primary spermatogonia. Intact March animals had mitotic indices higher than January animals. GnRHA treatment elicited an increase of the mitotic index in both intact and hypophysectomized animals. High temperature potentiated the GnRHA effect while low temperature favored pars distalis treatment. In conclusion, the present results are consistent with the fact that in the frog, R. esculenta, the magnitude of spermatogonial proliferation is temperature dependent, and for the first time it is shown that GnRH-like substances have direct stimulatory effect on the mitotic activity of the primary spermatogonia in a vertebrate. PMID- 3089763 TI - Involvement of growth hormone (GH)-releasing factor in GH secretion induced by serotoninergic mechanisms in conscious rats. AB - A possible role of hypothalamic GH-releasing factor (GRF) in GH secretion induced by serotoninergic stimuli was investigated in conscious freely moving rats with a passive immunization technique. Either iv injection of 5-hydroxy-L-tryptophan (1 mg/100 g BW) or intracerebroventricular injection of serotonin (10 micrograms/rat) caused an increase in plasma GH in rats treated with normal rabbit serum (0.5 ml/rat, iv) 30 min previously. Injection of rabbit antiserum specific for rat GRF (0.5 ml/rat, iv, 30 min previously) blunted the plasma GH increase induced by 5-hydroxy-L-tryptophan or serotonin in these animals. These results suggest that GH secretion induced by serotoninergic mechanisms is mediated, at least in part, by hypothalamic GRF in the rat. PMID- 3089764 TI - Effects of aging on the in vitro release of gonadotropin-releasing hormone. AB - Secretion of GnRH from mediobasal hypothalami (MBH) of old (23 month) and young (2 month) male rats was studied in an in vitro superfusion system. GnRH efflux from both old and young MBH increased in response to stimulation with 20 microM norepinephrine and 40 microM naloxone; however, both basal and stimulated GnRH release were reduced from MBH of old rats despite similar hypothalamic GnRH content. The diminished basal secretion and responsiveness to two major stimuli of the GnRH neuron may be important in the well-known involution of the hypothalamic-pituitary testicular axis in aging male rats. PMID- 3089765 TI - In vivo studies with growth hormone (GH)-releasing factor and clonidine in rat pups: ontogenetic development of their effect on GH release and synthesis. AB - The demonstration that GH-releasing factor (GRF) stimulates GH synthesis and release in rat pups prompted studies to evaluate the effects on the same indices of clonidine (CLO), an alpha 2-adrenoceptor and potent GH secretagogue, purported to act in adult rats via GRF release. Our first aim was to ascertain whether CLO elicits GH release in rat pups via GRF, and if this is the case, to evaluate the ontogenetic development in 1- to 10-day-old pups of the GH response to acute CLO or GRF administration and, finally, the effects of short term CLO or GRF treatment on plasma and pituitary GH concentrations and on the GH response to an acute challenge with the homologous secretagogue. CLO (15 micrograms/100 g BW, sc) induced a clearcut GH rise in 10-day-old rats but not in pups pretreated with a specific anti-GRF serum. Moreover, unlike GRF (10(-8) M), CLO (10(-6) to 10(-5) M) did not stimulate GH release in vitro from anterior pituitaries of 10-day-old rats. In 1-day-old rats, neither CLO (15 micrograms/100 g BW, sc) nor GRF (20 ng/100 g BW, sc) stimulated GH release, whereas significant GH stimulation was elicited by GRF, but not CLO, in 5-day-old rats and by both secretagogues in 10 day-old rats. Short term treatment with CLO (15 micrograms/100 g BW, sc, twice daily) or GRF (20 ng/100 g BW, sc, twice daily) on postnatal days 1 through 5 did not modify either plasma or pituitary GH concentrations 14 h after the last drug administration, but did so when either secretagogue was administered on postnatal days 5 through 9. Finally, an acute challenge with GRF, but not with CLO, induced a further rise in the already elevated plasma GH levels of pups pretreated from postnatal day 5 through 9, but neither secretagogue did so in pups pretreated from postnatal days 1 to 5. Viewed together, these data indicate that in infant rats CLO releases GH via GRF release and that the somatotropes respond earlier to GRF (5 days) than the GRF-secreting structures do to alpha 2-adrenergic stimulation (10 days). Both GRF and CLO stimulate GH synthesis when administered repeatedly. However, whereas repeated GRF treatment has a priming effect on the somatotropes, CLO does not, probably because of down-regulation of hypothalamic alpha 2-adrenoceptors. PMID- 3089766 TI - Immunolocalization of the thyrotropin-releasing hormone prohormone in the rat central nervous system. AB - The distribution of immunoreactive TRH prohormone in the rat central nervous system was studied by immunocytochemistry using an antiserum raised against a synthetic decapeptide hypothesized to represent a portion of the mammalian TRH precursor protein. Reaction product was identified in several regions of the brain in a distribution typical of that previously described for the tripeptide. In contrast to TRH, however, immunoreactive pro-TRH was largely confined to neuronal perikarya and only rarely seen in axons or axon terminals. In addition, immunoreactive pro-TRH was present in portions of the telencephalon and brainstem where TRH has not previously been described in neurons by immunocytochemistry. These studies indicate that in most regions of the brain the TRH prohormone is rapidly processed within the cell soma and not during axonal transport, and raise the possibility that in certain regions of the brain processing of the prohormone may be to non-TRH peptides, which may be of biological importance. PMID- 3089767 TI - Biosynthesis of cellular and secreted proteins during follicle-stimulating hormone-induced granulosa cell differentiation. AB - The synthesis of cellular and secreted proteins by differentiating granulosa cells from diethylstilbestrol-treated immature rats was studied by one- and two dimensional polyacrylamide gel electrophoresis. In cultured granulosa cells, FSH altered the relative biosynthesis of specific cellular and secreted proteins in a concentration- and time-dependent manner. The incorporation of [35S]methionine into cellular proteins of Mr 42,000, 48,000, and 58,000 was enhanced by increasing amounts of the gonadotropin, whereas the labeling of a 44,000 Mr protein was reduced. Similarly, FSH increased the labeling of secreted proteins with relative Mr of 16,000, 17,000, 20,000, 25,000, 36,000, 41,000, 46,000, 111,000, and 153,000, and decreased that of proteins with Mr of 38,000, 48,000, 191,000, and 250,000. The expression of specific proteins was related to the degree of cellular maturation, since some proteins were newly synthesized during the early stages of granulosa cell development (less than 6 h), whereas others were more evident in the middle (24 h) or later (48 h) phases of culture. Also, the level of specific protein synthesis was variable since certain proteins were progressively produced during culture, and the biosynthesis of others fluctuated or was reduced during development. The effects of FSH on protein synthesis were mimicked by other cAMP-inducing ligands, including cholera toxin, forskolin, and 8-bromo-cAMP. Removal of FSH at 24 h of culture was followed by reversion of the protein biosynthetic pattern at 48 h to that of control cells, indicating that continued exposure to the gonadotropin is required during development. Cells cultured in the absence of ligands for 24 h synthesized proteins characteristic of differentiated cells when subsequently cultured with forskolin. These results indicate that FSH selectively alters the biosynthesis of cell-associated and secreted proteins during granulosa cell maturation. The characterization of these gene products and the mechanisms controlling their expression should ultimately clarify the sequential events involved in the hormonal regulation of granulosa cell development. PMID- 3089768 TI - Androgen modulation of follicle-stimulating hormone-induced granulosa cell steroidogenesis in the primate ovary. AB - The role of androgen in regulating FSH-induced steroidogenesis in primates was investigated in granulosa cell cultures from reproductively suppressed (acyclic) marmoset monkeys. Progesterone accumulation and induction of aromatase activity were measured during a 48-h culture of granulosa cells (isolated from 0.5-1.0 mm diameter follicles) in medium 199 containing human (h) FSH and/or various sex steroids. Steroidogenesis in control cultures was minimal, but the presence of hFSH (0.3-100 ng/ml) caused dose-dependent stimulation. Maximal responses (mean +/- SE) were observed with 30 ng/ml of hFSH (aromatase, 1.0 +/- 0.2 pmol estradiol/10(3) cells X 3 h; progesterone, 4.5 +/- 0.8 pmol/10(3) cells X 48 h) and were 100 times basal values. The presence of testosterone (10(-6)M) during the 48-h culture enhanced the responses to hFSH two- to six-fold over the range 0.3-3.0 ng hFSH/ml. In the presence of a submaximal stimulatory dose of hFSH (3 ng/ml), the effects of testosterone on granulosa cell steroidogenesis were dose related. Maximum responses were obtained with doses of testosterone between 10( 8) and 10(-7)M. Similar dose-dependent effects were found with 5 alpha dihydrotestosterone (a non-aromatizable androgen), but not with estradiol, suggesting specific androgen synergism with FSH. Maximal aromatase activity induced after in vitro treatment with hFSH approached that in granulosa cells freshly isolated from a preovulatory follicle of a cyclic animal. These results demonstrate steroid modulation in vitro of FSH-responsive function, similar to that observed in rodent granulosa cells. Therefore, androgen may play a local role in the regulation of FSH-stimulated granulosa cell function during follicular development in primates. PMID- 3089769 TI - Pro-dynorphin is endogenous to the anterior pituitary and is co-localized with LH and FSH in the gonadotrophs. AB - Pro-dynorphin peptides have been shown to exist in the anterior lobe of the pituitary gland. The dynorphin in the anterior lobe is distinct from that which is co-localized with vasopressin in the magnocellular system in both post translational processing and regulation of release. Here, we report on the existence of pro-dynorphin mRNA, approximately 2400 nucleotides in length, in the anterior lobe. Furthermore, we present immunocytochemical evidence for the co existence of dynorphin, LH and FSH in a subset of gonadotrophs. These findings suggest a possible role of pro-dynorphin products in the regulation of the hypothalamic-pituitary-gonadal axis. PMID- 3089770 TI - Percutaneous endoscopic gastrostomy in patients with head and neck cancer. AB - A percutaneous endoscopic gastrostomy (PEG) was performed in 19 patients with cancers of head or neck. A commercially available gastrostomy set was used, but slight modifications were necessary in 4 patients. No serious complications were observed. The correct position and lack of any leak of gastric contents was verified by fluoroscopy in each case. These results confirm the experience of other groups, showing that the present technique of the PEG is reasonably safe and easy to perform. PMID- 3089771 TI - Analysis of the interlaboratory and intralaboratory reproducibility of the enhancement of simian adenovirus SA7 transformation of Syrian hamster embryo cells by model carcinogenic and noncarcinogenic compounds. AB - The intralaboratory and interlaboratory reproducibility of a DNA virus (SA7) transformation enhancement assay was investigated using nine carcinogenic and noncarcinogenic compounds representing a variety of chemical classes. By the use of standardized procedures designed to limit assay variables, replicate assay data were collected in two independent laboratories and analyzed for concurrence. The carcinogens, 7,12-dimethylbenz(a)anthracene, benzo(a)pyrene, and N-methyl-N' nitro-N-nitrosoguanidine yielded reproducible dose-dependent cytotoxicity and positive transformation effects (defined as statistically significant [p less than or equal to 0.05] enhancement of virus transformation at two or more consecutive dose levels) in all experiments in both laboratories. The carcinogens lead chromate, diethylnitrosamine, 4-nitroquinoline-N-oxide, and 2 acetylaminofluorene demonstrated enhancement of SA7 transformation at two or more dose levels in 40-50% of the assays. The noncarcinogenic structural analogs anthracene and pyrene consistently did not produce positive assay responses when tested at dose levels up to the limits of solubility. Good interlaboratory concurrence was demonstrated for these model compounds in the Syrian hamster embryo cell-SA7 assay. PMID- 3089772 TI - In vitro induction of sister chromatid exchanges and chromosomal aberrations in peripheral lymphocytes of the oyster toadfish and American eel. AB - A series of experiments was conducted to characterize the proliferation of oyster toadfish lymphocytes in medium containing 5-bromodeoxyuridine (BrdUrd) and to determine the effectiveness of cytogenetic endpoints for assessing the genotoxic effects of in vitro exposure of toadfish and eel lymphocytes to known mammalian clastogens. Although the rate of proliferation of toadfish lymphocytes was low compared to that of mammalian lymphocytes, the effects of increasing BrdUrd concentrations were similar, in that proliferation exhibited a concentration dependent inhibition for concentrations above 10 microM BrdUrd, and sister chromatid exchange (SCE) frequencies exhibited a concentration-dependent increase for concentrations above 100 microM BrdUrd. Mitomycin C (MMC) and ethylene dibromide (EDB) induced concentration-dependent increases in chromatid-type exchange and SCE frequencies with least effective concentrations (control SCE frequency divided by the slope of the least-squares line) for SCE induction by MMC (6.8 X 10(-9) M) and EDB (2.6 X 10(-4) M) that were comparable to or slightly lower than those that have been obtained with mammalian in vitro systems. In vitro exposure of toadfish lymphocytes to dimethoate (DIM) induced a concentration-dependent increase in SCE frequency with a least effective concentration of 2.8 X 10(-3) M that was much higher than that observed with mammalian in vitro systems. In vitro exposure of American eel lymphocytes to MMC also induced a concentration-dependent increase in the frequency of chromosomal aberrations and SCEs with a least effective concentration for SCE induction of 2.0 X 10(-9) M. These results indicate that cytogenetic endpoints can be effectively scored with cultured lymphocytes from these and perhaps other fish species with comparable karyotypes that contain an average of at least 0.07 pg DNA/chromosome. PMID- 3089773 TI - Acute toxicity of Microcystis aeruginosa and its cardiovascular effects. AB - The acute toxicity of a water extract from unialgal-cultured blue-green alga Microcystis aeruginosa M228 on mice and rats was studied. The mice intraperitoneally injected with the extract became lethargic and piloerection was seen. Terminally their ears, tails, limbs, and eyes became chalky white. The LD50 value of the extract for mice was estimated at 14.4 mg dry wt of cells/kg and that of rats was 67.4 mg/kg. Tachycardia was shown in the mice injected with the extract. A value of LD50 of coadministration of the extract and phenoxybenzamine in mice was significantly larger than that of the extract alone and survival time of mice injected with the extract and phenoxybenzamine was prolonged. These results suggest that the extract of the alga may take the acute toxic effects via the sympathetic nervous system. PMID- 3089774 TI - Heart rate changes caused by varying the oxygen supply to isolated hind legs of rats. AB - In a rat with an isolated hind leg circulation perfused with varying tyrode solutions, heart rate (HR) changes were studied in dependence of VO2 in the isolated hind leg and of PCO2, [K+], pH and lactic acid concentration ([Lac]) measured in the venous outflow of the isolated hind leg. In experimental series I the inflow PO2 (PiO2) was kept constantly high (either about 65 or 72 kPa). The perfusion pressure alternated between 16 and 24 kPa leading to flow rates in isolated hind legs (Qa) from 30 to 50 ml . 100 g-1 . min-1. The VO2 depended on the momentary Qa (flow-limited oxygen uptake). The [K+] and [Lac], the pH and the AVDO2 remained nearly constant while the PCO2 was lower at small flow rates. The HR decreases some 4 min after initial enhancement of Qa and VO2. Series II comprised experiments with low flow rates and a medium oxygen supply (Qa = 2.5 17.4 ml . 100 g-1 . min-1), PiO2 = 17.5-62.7 kPa). The VO2 ranged between 0.02 and 0.2 ml . 100 g-1 . min-1. The [K+] and [Lac], the PCO2 and the HR increased while the pH decreased. The [Lac] in the outflow showed a strong dependence on oxygen uptake and--at a weak oxygen supply--on the time. Cross-correlation analyses between the parameters confirmed that the HR was best temporally correlated to the [Lac] in the outflow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089775 TI - Polysaccharide from coccoliths (CaCO3 biomineral). Influence on crystallization of calcium oxalate monohydrate. AB - A polysaccharide associated with coccoliths of the marine alga Emiliania huxleyi (coccoliths are elaborately shaped calcite biominerals) was isolated and its influence on the crystallization of calcium oxalate monohydrate crystals was studied. Crystallization was monitored in a carefully controlled system by measuring the incorporation of 45Ca tracer from a supersaturated solution into seed crystals of calcium oxalate monohydrate in the absence and in the presence of polysaccharide. The method allowed differentiation between effects on solubility, growth and agglomeration of crystals. At the very low concentrations used in this study, the polysaccharide had no significant effect on the solubility product; it strongly inhibited the growth and strongly stimulated the agglomeration of the crystals. Thus, the two processes of growth and agglomeration, being both crystal-surface-related processes, may react in opposite directions upon surface adhesion of the additive. This finding opens new insights on how a mineralization process may be controlled. The inhibitory effect on growth is shown to proceed through a monolayer type of adsorption of the polysaccharide onto the crystal surface. The portion of the polysaccharide used for the stimulatory effect on agglomeration shows a different type of adsorption, whereby less crystal surface is covered per molecule of polysaccharide. This strongly suggests, that the mechanism whereby agglomeration is stimulated operates through 'viscous binding', with the polysaccharide bridging the gap between two crystal surfaces. In the discussion these findings are related to some possible biological functions of the polysaccharide. PMID- 3089776 TI - Characterization of functional domains in human tissue-type plasminogen activator with the use of monoclonal antibodies. AB - Two murine monoclonal antibodies (MA-2G6 and MA-1C8), secreted by hybridomas obtained by fusion of myeloma cells with spleen cells from mice immunized with human tissue-type plasminogen activator (t-PA), inhibited the activity of t-PA on fibrin plates. MA-2G6 inhibited the amidolytic activity of t-PA and did not react with t-PA in which the active-site serine was blocked with diisopropylfluorophosphate nor with t-PA in which the active-site histidine was alkylated by reaction with D-Ile-Pro-Arg-CH2Cl. This indicated that MA-2G6 is directed against an epitope covering the active site of t-PA. MA-1C8 did not inhibit the amidolytic activity of t-PA, but abolished both the binding of t-PA to fibrin and the stimulatory effect of fibrin on the activation of plasminogen by t-PA. Thus MA-1C8 is directed against an epitope which covers the fibrin binding site of t-PA. The A and B chains of partially reduced two-chain t-PA were separated by immunoadsorption on immobilized MA-1C8 and MA-2G6. The purified B chain reacted with MA-2G6 but not with MA-1C8 and activated plasminogen following Michaelis-Menten kinetics with kinetic constants similar to those of intact t-PA (Km = 100 microM and kcat = 0.02 s-1). However, fibrin or CNBr-digested fibrinogen did not stimulate the activation of plasminogen by the B chain. The purified A chain reacted with MA-1C8 but not with MA-2G6. It bound to fibrin with an affinity similar to that of intact t-PA but did not activate plasminogen. It is concluded that the active center of t-PA is located in the B chain and the fibrin-binding site in the A-chain. Both functional domains are required for the regulation by fibrin of the t-PA-mediated activation of plasminogen. PMID- 3089777 TI - Biosynthesis of rat-liver pI-5.0 esterases in cell-free systems and in cultured hepatocytes. AB - Rat liver esterases focusing at pH 5.0 (referred to below as pI-5.0 esterases) are structurally related glycoproteins which differ slightly in their mobility in sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE). They reside in the lumen of the endoplasmic reticulum. We have studied their biosynthesis in cell-free systems programmed by total liver RNA, using sheep and rabbit antibodies to isolate the translation products related to these enzymes. Our results show that they are assembled as a precursor polypeptide chain (62 kDa) larger than the mature proteins. The pI-5.0 esterase mRNA could be extracted from bound but not free polysomes. Reticulocyte lysates supplemented with dog pancreas microsomes produced four esterase-related components in segregated form (61, 60, 58 and 56 kDa). The largest three correspond in electrophoretic mobility to the mature enzymes. They are glycoproteins that bind to concanavalin A, and can be reduced to the size of the shortest component by endo-beta-N acetylglucosaminidase H (endo-H). Immunoprecipitation after biosynthetic labeling of the proteins in cultured hepatocytes also gave three glycosylated components that had the same mobility in SDS-PAGE as the mature enzymes. When tunicamycin was present in the culture medium, a single immunoprecipitable form was observed. Its apparent Mr was similar to that of the unglycosylated pI 5.0 esterase form synthesized in vitro in the presence of dog pancreas microsomes. Thus the biosynthesis of these esterases has characteristics in common with that of numerous secretory proteins, except for the rather large difference in size (approximately equal to 6 kDa) resulting from the proteolytic processing of their in-vitro-synthesized precursor. PMID- 3089778 TI - Upstream sequences modulate in vitro transcription from Drosophila yolk protein genes I and II. AB - A Drosophila transcription system was employed to study transcription in vitro from templates carrying yolk polypeptide I and II (YPI, YPII) promoter regions. The transcription start sites of YPI and YPII genes are linked by 1225 base pairs of intergenic DNA and the genes are transcribed in divergent directions. Transcription was studied in vitro from templates carrying YPI or YPII promoter regions separately. We have successively deleted intergenic DNA upstream of the YPI or the YPII transcription start site and have assayed the dependence of transcription efficiency an template concentration. The results indicate that in vitro YPI and YPII transcript synthesis is controlled by separate cis-acting DNA sequence elements, which are located between 86 and 159 base pairs upstream of the YPI transcription start site and between 161 and 341 base pairs upstream of the YPII transcription start site. These elements stimulate in vitro transcription up to fivefold. Transcription was also studied with templates which contained both YP promoters. The transcription data indicate that the intergenic DNA contains additional DNA motif(s), which apparently modulate in vitro transcription coordinately from both YP promoters in an orientation-dependent manner. PMID- 3089779 TI - Purification and characterization of Bacillus coagulans oligo-1,6-glucosidase. AB - A p-nitrophenyl-alpha-D-glucopyranoside-hydrolyzing oligo-1,6-glucosidase of Bacillus coagulans ATCC 7050 (facultative thermophile) was purified to homogeneity. The relative molecular mass, Stokes radius, sedimentation coefficient at 20 degrees C in water, molecular absorption coefficient at 280 nm and pH 6.8, and isoelectric point were estimated as 60 000, 3.29 nm, 4.8 X 10( 13) s, 1.34 X 10(5) M-1 cm-1, and 4.3, respectively. The amino-terminal amino acid was threonine. There was no common antigenic group between the enzyme and each of its homologous counterparts from Bacillus cereus ATCC 7064 (mesophile) and Bacillus thermoglucosidasius KP 1006 (obligate thermophile). These oligo-1,6 glucosidases strongly resembled one another in their amino acid composition, except that the proline content increased with the elevation of thermostability in the order, mesophile----facultative thermophile----obligate thermophile enzymes. PMID- 3089780 TI - Phosphorylase kinase from chicken skeletal muscle. Quaternary structure, regulatory properties and partial proteolysis. AB - Phosphorylase kinase has been purified from white and red chicken skeletal muscle to near homogeneity, as judged by sodium dodecyl sulphate (SDS) gel electrophoresis. The molecular mass of the native enzyme, estimated by chromatography on Sepharose 4B, is similar to that of rabbit skeletal muscle phosphorylase kinase, i.e. 1320 kDa. The purified enzyme both from white and red muscles showed four subunits upon polyacrylamide gel electrophoresis in the presence of SDS, corresponding to alpha', beta, gamma' and delta with molecular masses of 140 kDa, 129 kDa, 44 kDa and 17 kDa respectively. Based on the molecular mass of 1320 kDa for the native enzyme and on the molar ratio of subunits as estimated from densitometric tracings of the polyacrylamide gels, a subunit formula (alpha' beta gamma' delta)4 has been proposed. The antiserum against the mixture of the alpha' and beta subunits of chicken phosphorylase kinase gave a single precipitin line with the chicken enzyme but did not cross react with the rabbit skeletal muscle phosphorylase kinase. The pH 6.8/8.2 activity ratio of phosphorylase kinase from chicken skeletal muscle varied from 0.3 to 0.5 for different preparations of the enzyme. Chicken phosphorylase kinase could utilize rabbit phosphorylase b as a substrate with an apparent Km value of 0.02 mM at pH 8.2. The apparent V (18 mumol min-1 mg-1) and Km values for ATP at pH 8.2 (0.20 mM) were of the same order of magnitude as that of the purified rabbit phosphorylase kinase b. The activity of chicken phosphorylase kinase was largely dependent on Ca2+. The chicken enzyme was activated 2-4-fold by calmodulin and troponin C, with concentrations for half-maximal activation of 2 nM and 0.1 microM respectively. Phosphorylation with the catalytic subunit of cAMP-dependent protein kinase (up to 2 mol 32P/mol alpha beta gamma delta monomer) and autophosphorylation (up to 8 mol 32P/mol alpha beta gamma delta monomer) increased the activity 1.5-fold and 2-fold respectively. Limited tryptic and chymotryptic hydrolysis of chicken phosphorylase kinase stimulated its activity 2-fold. Electrophoretic analysis of the products of proteolytic attack suggests some differences in the structure of the rabbit and chicken gamma subunits and some similarities in the structure of the rabbit red muscle and chicken alpha'. PMID- 3089782 TI - Effect of polyamines on in vitro reconstitution of ribosomal subunits. AB - The effect of polyamines on in vitro reconstitution of Escherichia coli 30S and 50S ribosomal subunits has been studied. Spermidine stimulated the reconstitution of 30S particles from 16S rRNA lacking the methyl groups on two neighboring adenines and total proteins of 30S subunits at least 1.6-fold. The reconstitution of 30S particles from normal 16S rRNA and total proteins of 30S subunits exhibited only slight spermidine stimulation. However, the optimal Mg2+ concentration of the reconstitution was decreased from 20 mM to 16 mM in the presence of 3 mM spermidine. In the absence of spermidine the assembly of 30S particles from normal 16S rRNA was more rapid than the assembly from 16S rRNA lacking the methyl groups on two neighboring adenines. The reconstitution of 50S particles from 23S and 5S rRNA and total proteins of 50S subunits was not influenced greatly by spermidine. Gel electrophoresis results, from reconstitution experiments of 30S particles from 16S rRNA lacking the methyl groups on two neighboring adenines and total proteins of 30S subunits, showed that the assembly of S1 and S9 proteins to 23S core particles was stimulated by spermidine during reconstitution. The relationship of polyamine effects on in vitro ribosome assembly from its constituents to in vivo ribosome assembly is discussed. The reconstitution of Bacillus subtilis 30S particles from 16S rRNA and total proteins of 30S subunits was also stimulated approximately 1.3-fold by 3 mM spermidine. PMID- 3089781 TI - Identification and characterization of the 35-kDa beta subunit of guanine nucleotide-binding proteins by an antiserum raised against transducin. AB - Antisera were raised against the retinal guanine-nucleotide-binding protein (N protein), transducin, purified from bovine rod outer segments. Sera obtained after repeated injections of antigen recognized all transducin subunits (alpha, beta and gamma). One antiserum, tested for cross-reactivity with non-retinal N proteins, was found to cross-react with the beta subunits of the ubiquitously occurring N-proteins, Ns and Ni, but not with their respective alpha and gamma subunits. The antiserum also cross-reacted with the beta subunit of the recently identified N-protein, No, which has been found in high abundance in the central nervous system. These data support the similarity of the beta subunits of the N proteins identified so far. Purification of N-proteins from porcine cerebral cortex without the use of activating ligands yielded fractions containing the isolated alpha subunit of No, free beta gamma complex, Ni, No and fractions containing both N-proteins in various proportions. The purity of the preparations was at least 80% as judged by Coomassie-blue-stained SDS gels. No pure Ns was obtained. Use of the transducin antibody during the course of the purification revealed that the beta subunits coeluted from a gel filtration column largely with the alpha subunits of Ni and No but were hardly detectable in fractions that were able to reconstitute Ns activity into membranes of an Ns-deficient cell line (S49 cyc- lymphoma cells). This indicates that in the central nervous system the concentrations of Ni and No are of magnitudes higher than that of Ns. Two dimensional gel electrophoresis of N-proteins, purified from porcine cerebral cortex, resulted in the resolution of two major peptides in the 35-kDa region, which differed in their pI values and were identified as beta subunits by the use of the antiserum. Identical results were achieved using crude cholate extracts from membranes of the same tissue instead of purified proteins. The occurrence of different beta subunits may be explained by posttranslational N-protein modification. PMID- 3089784 TI - Primary structure of a new tetraantennary glycan of the N-acetyllactosaminic type isolated from human factor VIII/von Willebrand factor. AB - N-Glycosidically linked glycopeptides released by mild alkaline treatment of human factor VIII/von Willebrand factor (FVIII/vWF) were fractionated by serial affinity chromatography on columns of Sepharose linked to concanavalin A (ConA) and Lens culinaris agglutinin (LCA). The fraction which is not retained on ConA Sepharose, but eluted from LCA-Sepharose contains a pure minor glycopeptide which was structurally analysed. Based on the results of methylation analysis and 500 MHz 1H-NMR spectroscopy, the following structure is proposed: (Formula: see text). PMID- 3089783 TI - Control of ammonia distribution ratio across the liver cell membrane and of ureogenesis by extracellular pH. AB - The mechanisms involved in ammonia uptake by rat liver cells and the effects of changes in extracellular pH have been investigated in vivo and in vitro. When NH4Cl solutions were infused in the hepatic portal vein, ammonia uptake by the liver was practically quantitative up to about 1 mM in afferent blood. Ammonia transfer into hepatocytes was extremely rapid: for 2 mM ammonia in external medium, the intracellular concentration reached 5 mM within 10 s. Comparatively, [14C]methylamine influx was slower and the cell concentrations did not reach a steady-state level, probably in relation with diffusion into the acidic lysosomal compartment. Intracellular accumulation of ammonia was dependent on the delta pH across the plasma membrane: the distribution ratio (internal/external) was about 1 for an external pH of 6.8 and about 5 at pH 8. Urea synthesis was maximal at physiological pH and markedly declined at pH 7.05. This inhibition was not affected by manipulation of bicarbonate concentrations in the medium, down to 10 mM. Additional inhibition of ureogenesis by 100 microM acetazolamide was also observed, particularly at low concentrations of bicarbonate in the medium. Inhibition of ureogenesis when extracellular pH is decreased could be ascribed to a lower availability of the NH3 form. Assuming that NH3 readily equilibrates between the various compartments, the availability of free ammonia for carbamoyl phosphate synthesis could be tightly dependent on extracellular pH. PMID- 3089785 TI - Chromatin structure and induction-dependent conformational changes of human interferon-beta genes in a mouse host cell. AB - Multiple copies of a human interferon-beta gene introduced into a mouse host cell line can be activated by induction with double-stranded RNA. Several induction dependent changes of the chromatin structure could be traced by mapping techniques using four different agents [DNase I, micrococcus nuclease, bromoacetaldehyde and methidiumpropyl-EDTA X iron(II)]. Our data show that all copies of the interferon gene have adopted a very similar conformation in the host cell and respond to the inducing stimulus in a highly synchronous fashion. Detailed induction-specific changes were observed best with the chemical reagents which disclose a specific hypersensitive site within a sequence that has been shown to be required for the induction process (around position -80) and three other regions which, in addition to the transcribed region itself, gain single strand character by an auxiliary process which can be mimicked by the addition of butyrate to the medium and may therefore involve histone hyperacetylation. Six discrete 'phased' nucleosomes are present upstream from the gene and are modulated by induction. At least four nucleosomes are located downstream. The interferon genes are largely protected from micrococcus nuclease in the inactive state. Gene activation increases access to micrococcus nuclease and DNase I indicating gross conformational changes on a higher level of chromatin structure. PMID- 3089786 TI - Lipoic acid is the site of substrate-dependent acetylation of component X in ox heart pyruvate dehydrogenase multienzyme complex. AB - The recently characterized Mr-50000 polypeptide associated with mammalian pyruvate dehydrogenase complex, referred to as component or protein X, was shown to incorporate N-ethylmaleimide only in the presence of pyruvate or NADH. Component X, modified with N-ethyl[2,3-14C]maleimide in the presence of pyruvate, was isolated and subjected to acid hydrolysis. The radioactive products were resolved on an amino acid analyser and these coeluted with products from similarly modified and hydrolysed lipoate acetyltransferase. Preincubation of pyruvate dehydrogenase complex with pyruvate or NADH and acetyl-CoA resulted in a time-dependent diminution of incorporation of radiolabelled N-ethylmaleimide into component X and lipoate acetyltransferase and, correspondingly, in the extent of inhibition of overall complex activity by N-ethylmaleimide. PMID- 3089787 TI - The position of the oligosaccharide side-chains of phytohemagglutinin and their accessibility to glycosidases determines their subsequent processing in the Golgi. AB - Phytohemagglutinin (PHA), the glycoprotein lectin of Phaseolus vulgaris has two types of asparagine-linked oligosaccharides per polypeptide: a high-mannose chain with the formula (Man)8-9(GlcNAc)2 on Asn12 and a modified chain with fewer mannose residues and additional fucose and xylose residues on Asn60. Glycosylation of PHA is a cotranslational process, which occurs in the endoplasmic reticulum, and newly synthesized PHA has two high-mannose chains. Transport of PHA to the protein bodies via the Golgi complex is accompanied by the modification of one of the two high-mannose chains. Why is only one chain modified, while the other remains in the high-mannose configuration? By determining the effect of digestion with various glycosidases (alpha-mannosidase, endo-beta-N-acetylglucosaminidase H and endo-beta-N-acetylglucosaminidase F) on native and denatured PHA we obtained evidence consistent with the interpretation that the accessibility of oligosaccharide chains to modifying enzymes is of major importance in determining whether a high-mannose chain becomes modified or not. The high-mannose chain of mature undenatured PHA is only partially accessible to glycosidases, while PHA obtained from the endoplasmic reticulum has one high mannose chain, which is readily accessible to alpha-mannosidase and endoglycosidases H and F. We show that this readily accessible chain is in the same position on the polypeptide (Asn60) as the modified oligosaccharide on mature PHA. Thus, accessibility of the oligosaccharide side-chains to processing enzymes in the Golgi determines whether a particular oligosaccharide side-chain is processed or not. PMID- 3089788 TI - Anomeric specificity of D-glucose metabolism in rat adipocytes. AB - The anomeric specificity of D-glucose metabolism was investigated in rat adipocytes exposed for 60 min at 8 degrees C to pure alpha- or beta-D-glucose or to equilibrated D-glucose. The rate of D-[5-3H]glucose utilization was higher with alpha- than beta-D-glucose. However, as judged from the oxidation of D-[1 14C]glucose and D-[6-14C]glucose anomers, the fraction of D-glucose catabolism occurring via the pentose cycle was higher with beta- than alpha-D-glucose. In the presence of equilibrated D-glucose, the utilization of alpha-D-[5-3H]glucose and the oxidation of both alpha-D-[1-14C]glucose and alpha-D-[6-14C]glucose were higher, relative to the anomer concentration, than the corresponding values for beta-D-glucose. It is concluded that the anomeric specificity of D-glucose metabolism is operative in adipocytes, even when they are exposed to equilibrated D-glucose. PMID- 3089789 TI - A new approach toward a pancreas-seeking zinc radiopharmaceutical. I. Accumulation of 65Zn-amino acid and aminopolycarboxylic acid complexes in pancreatic tissue slices. AB - There have been many attempts to develop zinc-containing radiopharmaceuticals for use as pancreas-seeking agents, but little consideration has been given to Zn complex structure as being a factor that contributes to Zn utilization by the pancreas. In the present study, various ligands having N-O donor groups (amino acids and aminopolycarboxylic acids) with variable numbers of coordination sites (2-6) were investigated with regard to the coordination of the radiometal Zn. As an experimental model, freshly prepared slices of rat pancreas were studied, and Sephadex-column chromatography analysis was also performed. The structure and stability of Zn complexes were found to affect the accumulation of Zn in pancreas slices. In particular, the administration of tetradentate ligand complexes of 65Zn-ethylenediamine-N,N'-diacetic acid (EDDA) and 65Zn-nitrilotriacetic acid (NTA) resulted in high Zn utilization in the pancreas. Also, Zn complexes of intermediate stability (as demonstrated by elution behavior at Sephadex-column chromatography) produced the best results. PMID- 3089790 TI - A new approach toward a pancreas-seeking zinc radiopharmaceutical. II. 62Zn-EDDA (ethylenediamine-N,N'-diacetic acid) for pancreas PCT imaging. AB - The functionality of various zinc complexes of amino acid derivatives as a zinc radiopharmaceutical for pancreas PCT imaging was tested using 65Zn, which has a long half-life, and 62Zn, which has a short half-life. Because of the favorable results obtained in previous in vitro pancreas section studies, the ability of those Zn complexes to retain their integrity in the presence of blood serum or in living organisms was screened using Sephadex column chromatography and mice biodistribution studies. A relationship between the structure and stability of Zn complexes played a determining role on the in vivo availability of Zn for the pancreas or liver. Among the Zn complexes tested, the tetra-coordinated structure of the Zn-EDDA complex at an equimolar ratio showed proper accumulation in the pancreas, inducing an appropriate pancreas PCT image in the dog with the positron emitter 62Zn-EDDA administered at 1 mg Zn/kg body weight. PMID- 3089791 TI - Scintigraphic control of bone-fracture healing under ultrasonic stimulation: an animal experimental study. AB - In a model of closed lower-leg fracture in rabbits and of secondary bone-fracture healing, scintigraphic control until biological healing was performed. Biological fracture healing was assumed for a region of interest (ROI)-activity ratio close to 1.0. After application of 99mTc-HEDP, 151 examinations were performed. ROI activity increased significantly until day 14 p.i. and reached the maximum value (Q = 6.44) on day 14 postfracture. Sixty-one lower leg fractures were treated by ultrasound from days 14-28 postfracture. These stimulated fractures were biologically healed on day 168 postfracture. The fractures that were not treated by ultrasound could not be detected by scanning after day 203 postfracture. PMID- 3089794 TI - True precocious puberty of a girl with hamartoma of the CNS successfully treated by operation. AB - A girl with precocious puberty due to a hypothalamic hamartoma is presented. At the age of 0.41 years vaginal bleeding was documented and signs of puberty were noted: PHIII, BII according to Tanner. The bone age was 1.3 years, and height velocity rose from the 50th to 90th percentile. Plasma concentrations of LH (5.85 mU/ml), FSH (3.29 mU/ml), growth hormone (30 ng/ml), and oestradiol (90 pg/ml) were elevated. The results of a neurological examination including an EEC recording as well as a skull roentgenogram, were unremarkable. The visual evoked potentials were grossly abnormal. A native and contrast CT scan visualized a tumour close to the suprasellar cisterna reaching the chiasma opticum. At the age of 1.2 years the tumours was removed. Histologically the tissue was identified as a hamartoma. Immediately after the operation vaginal bleeding ceased, pubertal development regressed, bone age did not advance any further, the visual evoked potentials normalized and the contrast CT did not show any tumour mass. The levels of LH, FSH, growth hormone and oestradiol 4 months post operation were decreased as follow: LH: 1.14 mU/ml, FSH: 0.70 mU/ml, GH: 15.1 ng/ml, oestradiol: 10 pg/ml. However, there was an increase of FSH (3 mU/ml) 1 year after the operation. No secondary sexual characters reappeared. PMID- 3089792 TI - Fatty acid composition of plasma lipids in Nigerian children with protein-energy malnutrition. AB - The fatty acid (FA) composition of the main plasma lipids was analysed in eight well-nourished, generally healthy Nigerian children aged 14.1 +/- 7.2 months and in 17 malnourished children (8 marasmus, 9 kwashiorkor) aged 14.6 +/- 3.8 months within the first 2 days of admission at the Dept. of Child Health, University of Benin. In comparison to the control group, the malnourished children showed a marked decrease of polyunsaturated FA with low linoleic acid, mainly in sterol esters (STE), and severely reduced linoleic acid metabolites, including arachidonic acid, in all lipid fractions. omega-3-FA were not altered except for a reduction of docosapentaenoic and docosahexaenoic acids in phospholipids. Clearly increased values were found for saturated FA in STE and for the non essential monoenoic FA in all lipid classes. This pattern indicates the presence of essential fatty acid deficiency in the malnourished children. There was no significant difference between marasmus and kwashiorkor. Eight malnourished children were followed up in the early phase of recovery during hospital treatment 14.0 +/- 3.1 days after obtaining the first sample. Linoleic acid had increased again in STE, but its metabolites were as low or even lower than before. An impaired activity of delta-6-desaturase, the rate limiting enzyme of linoleic acid metabolism, in suggested by elevated substrate-product-ratios of this enzyme in untreated children with protein energy malnutrition and in the early phase of recovery, which may be due to low insulin levels, protein and zinc deficiency. The trientetraen ratio (20:3 omega 9/20:4 omega 6) thus is not a reliable indicator of essential FA status in protein-energy malnutrition. PMID- 3089793 TI - Recovery from post-traumatic anterior pituitary insufficiency. PMID- 3089795 TI - Mitochondrial phosphoenolpyruvate carboxykinase deficiency. AB - A 3-month-old girl presented with anorexia, failure to thrive and drowsiness. She was mildly icteric with hepatomegaly and peripheral oedema. Disordered liver function tests were associated with the biopsy appearances of a giant cell hepatitis and with a Fanconi syndrome. At the age of 16 weeks she collapsed with profound hypoglycaemia. Fasting also provoked hypoglycaemia with lactic acidaemia. She became increasingly irritable and hypotonic and, although initially liver and renal function improved, she deteriorated and died of hepatocellular failure and septicaemia. A post-mortem revealed massive fatty degeneration of the liver. The activity of phosphoenolpyruvate carboxykinase in her cultured skin fibroblasts was 16% of controls. Her brother died at the age of 4 weeks of sudden infant death syndrome. PMID- 3089796 TI - Prenatal exclusion of purine nucleoside phosphorylase deficiency. AB - We report on the prenatal exclusion of purine nucleoside phosphorylase (PNP) deficiency in a fetus whose parents were known to be heterozygotes for the enzyme defect. Prenatal investigation was performed in the 16th week of gestation on amniotic fluid and cultured amnion cells using sensitive techniques. The results suggested that the fetus was either normal or a heterozygote. PNP activity in cord red cells confirmed the heterozygous status of the baby. PMID- 3089797 TI - Growth hormone releasing hormone (GH-RH, GRF)--an important new clinical tool. PMID- 3089798 TI - Listeria monocytogenes neonatal meningitis in The Netherlands. AB - As part of a collaborative study of the epidemiology of bacterial meningitis, the bacteriological data and some clinical features concerning neonates with Listeria monocytogenes meningitis were analysed for the period 1976-1982. In this group of 12 patients the case mortality rate was 17%. Seventeen per cent of the children weighed less than 2500 g at birth. Sixty-seven % of the cases occurred in the absence of any known risk factor. Listeria monocytogenes type IV B was isolated in 75% of the cases. PMID- 3089799 TI - Evaluation of the pituitary-thyroidal axis in newborns undergoing exchange transfusion. AB - To evaluate whether the hypothyroxinaemia, previously noted in hyperbilirubinaemic newborns immediately after exchange transfusion for Rh or AB0 incompatibility, was due to impairment in the secretion of thyroid stimulating hormone (TSH) by the pituitary, we studied the thyroid hormone response to thyrotropin releasing hormone (TRH) and compared this response to that seen in a control population of healthy neonates. All infants studied responded with a brisk TSH increase; 30 min after TRH injection the mean TSH concentration of the hyperbilirubinaemic patients was 37 microU/ml, ten times their basal level, which was not different from the value noted in the control population. No significant change in total thyroxine (T4), 3,5,3' triiodothyronine (T3), free thyroxine (FT4) or 3,3',5' triiodothyronine (rT3), (FT4) or (rT3) was noted after TRH administration in either group of neonates. In addition the effect of exchange transfusion on the thyroid axis of hyperbilirubinaemic newborns was evaluated. Before the exchange transfusion TSH, T4, rT3, T3 and FT4 levels were higher in the hyperbilirubinaemic newborns than in donor blood; immediately post-exchange transfusion TSH and T4 concentrations of the hyperbilirubinaemic neonates decreased significantly and remained significantly below pre-exchange values 30 h later. Newborns undergoing an exchange transfusion respond appropriately to TRH stimulation and seem to have an intact pituitary-thyroidal axis. PMID- 3089800 TI - Changes in thyroid function tests induced by 2 month carbamazepine treatment in L thyroxine-substituted hypothyroid children. AB - In five L-thyroxine-substituted hypothyroid children with partial epilepsy serum total thyroxine (T4) and free T4 (FT4) significantly (P less than 0.01) decreased following 2 months of carbamazepine (CBZ) administration (20 mg/kg per BW per day) from mean (+/- SD) values of 12.7 +/- 1.1 micrograms/dl and 15.5 +/- 1.8 pg/ml to mean values of 7.5 +/- 2.3 and 10.1 +/- 1.7, respectively. In all but one patient important changes in both serum total and free triiodothyronine (T3, FT3) were not observed; consequently T3:T4 and FT3:FT4 ratios significantly (P less than 0.05) increased in the whole series. Three subjects had post-treatment serum TSH that rose to hypothyroid levels parallel to a T4 decrease. The negligible thyroid hormone secretion and the unmodified T3-uptake (T3U) or T4 binding globulin (TBG) exclude direct effects of CBZ on thyroid gland and on carrier serum proteins, respectively. The findings observed, instead, might be due to accelerated T4 metabolic clearance together with augmented T4 to T3 conversion rate, as previously demonstrated for diphenylhydantoin. The sharp reduction in T4 and FT3 concentrations is the peripheral display of this event, which is associated with a decompensation of the metabolic status, as indicated by serum TSH enhancement. In all cases a supplement of L-thyroxine by itself was able to restore euthyroid TSH serum concentrations, suggesting that hypothyroidism in patients with partial epilepsy to whom CBZ had been administered requires a higher L-T4 substitutive regimen. PMID- 3089802 TI - Recombinant tumor necrosis factor: its effect and its synergism with interferon gamma on a variety of normal and transformed human cell lines. AB - Tumor Necrosis Factor (TNF), released by induced macrophages, causes tumor necrosis in animals, and preferentially kills transformed cells in vitro. Using pure, recombinant human TNF, we report here its cytotoxic action on several human transformed and non-transformed cell lines. Furthermore, remarkable synergism between TNF and interferon-gamma (IFN-gamma) was observed in a large number of human cell lines, especially breast, cervix and colon carcinomas. Some other human cell lines, not sensitive to TNF alone, became highly sensitive when IFN gamma was present as well. We could not demonstrate a synergism between TNF and IFN-gamma on any of the lymphoma/leukemia cell lines tested. All normal human, non-transformed diploid cell lines were insensitive to TNF even in the presence of IFN-gamma. This study also confirms the observation that inhibition of protein synthesis by metabolic drugs (e.g. actinomycin D) remarkably enhances the sensitivity of several target cell lines to cytolysis by TNF. PMID- 3089803 TI - Major histocompatibility gene complex-disease associations may reflect T cell mediated immunopathology. PMID- 3089801 TI - Selective immunoglobulin M deficiency associated with disseminated molluscum contagiosum. AB - A 16-year-old girl with disseminated molluscum contagiosum (MC) was found to have a very low level of serum IgM, elevated levels of IgG and IgA, and a high level of IgE. She had normal numbers of peripheral blood IgM+, IgG+ and IgA+ B lymphocytes but their terminal differentiation into plasma cells could not be induced by pokeweed mitogen (PWM) in vitro. On the other hand, the patient's T cells showed normal helper functions in the PWM system and normal interferon (IFN) production in vitro. However, the IgM+ B-cells can be induced to differentiate into IgM secreting cells by Epstein-Barr virus (EBV), suggesting that the genetic mechanism for synthesis of the component immunoglobulin proteins is present. T-cell functions were impaired, as shown by delayed type cutaneous hypersensitivity (DTH) and mitogen response. The data suggest that the selective IgM deficiency of the patient is due mainly to defects in B-cells at the terminal differentiation stage, but immunological abnormalities are present in both B and T-cell systems. Neutrophil functions examined were normal. MC was treated by intravenous injection of IFN without any side effects; however, no clinical improvement was achieved. PMID- 3089804 TI - Effect of short lasting hypoxia on the metabolic function of the perfused pig liver. Comparison of ischaemic and hypoxaemic hypoxia. AB - The effects of hypoxaemia and ischaemia were compared in the perfused pig liver. Decreased hepatic oxygen uptake, galactose elimination, ATP phosphorylation and increased lactate output occurred when the oxygen supply was diminished below 55% of the mean of controls. Below the control limits for oxygen uptake and oxidative phosphorylation, the change in the above variables were correlated to the degree of hypoxia, with no quantitative differences regarding ischaemic or hypoxaemic hypoxia. Galactose elimination was correlated to the ATP concentration (r = 0.81). After 80 min of hypoxia almost complete recovery was seen. It can be inferred from the data that other factors than oxygen diffusion into the liver cells may limit oxidative metabolism. Long and severe hypoxia may be required before irreversible cellular damage occurs in the liver. PMID- 3089806 TI - Renin, aldosterone and arginine vasopressin in patients with liver cirrhosis: the influence of ascites retransfusion. AB - Plasma renin activity (PRA), and concentrations of aldosterone (PAL) and arginine vasopressin (AVP) in plasma were determined in 15 patients with ascites due to cirrhosis. The concentrations in ascites were analyzed simultaneously. Six patients were studied during extracorporeal ascites retransfusion. All but one patient with ascites showed elevated PAL (642 +/- 255 pg ml-1) and PRA (43 +/- 26 ng ml-1 h-1); all had increased AVP (7.3 +/- 5.1 pg ml-1). A low ascites to plasma ratio was found for aldosterone (0.023 +/- 0.023), but not for AVP (0.71 +/- 0.82). Retransfusion resulted in a normalization of central venous pressure (CVP), urinary volume, sodium/potassium ratio in urine, PAL and PRA, but not of AVP, serum sodium concentration and urinary sodium excretion. PRA and PAL increased again after cessation of treatment, while urinary output, CVP and sodium/potassium ratio in urine decreased. The results support the 'underfilling' concept, but give evidence that, in addition, other factors must be involved in the impaired natriuresis in cirrhotic patients. They further support the concept of volume expansion and increased renal perfusion as reason for the therapeutic efficacy of ascites retransfusion. Previous diuretic treatment seems not to be of importance for altered hormone metabolism in liver cirrhosis. Storage in a third compartment may be a factor in the persistently elevated AVP levels. PMID- 3089805 TI - Renal prostaglandins E2 and F2 alpha throughout normal human pregnancy. AB - Twenty-five normal pregnant women were studied sequentially at 4-week intervals, beginning from weeks 8-16 until delivery. In eighteen women the study was repeated 6 weeks after delivery. The 24-h urinary excretion of PGE2 and PGF2 alpha, plasma renin activity (PRA), plasma aldosterone and fractional excretion of sodium (FENa) were measured at each visit. PGE2 and PGF2 alpha increased progressively throughout pregnancy (867 +/- 81 and 1048 +/- 94 ng 24 h-1 respectively, before week 15 and 1581 +/- 175 and 2625 +/- 305 ng 24 h-1, respectively, after week 35) and returned to normal values 6 weeks after delivery (748 +/- 107 and 1503 +/- 165 ng 24 h-1, respectively). PRA and aldosterone increased in a similar fashion, but values of prostaglandins did not correlate with those of PRA or aldosterone. PGE2 correlated directly with FENa but this correlation was weak. These results may suggest that tubulo-interstitial prostaglandins play a role in the regulation of sodium homeostasis during pregnancy. PMID- 3089807 TI - Effect of captopril on the cerebral circulation in chronic heart failure. AB - Cerebral blood flow (CBF) was investigated in 8 patients with chronic heart failure (CHF) (functional class III) and in twelve controls before and after administration of 6.25 mg and 25 mg captopril, respectively. In four controls, CBF was measured by the intracarotid xenon-133 (133Xe) injection technique using stationary external detectors, while inhalation of 133Xe and single photon emission computer tomography was used in the remaining cases. In the control group, the cerebral metabolic rate for oxygen was calculated from measurements of the arterio-venous oxygen difference as well. Mean CBF was significantly (P less than 0.01) lower in the patients with CHF as compared to our controls. Following captopril administration the mean arterial blood pressure decreased in the CHF patients, ranging from 5 to 40%. Three patients showed decreases of blood pressure to values of 56, 65, and 76 mm Hg, but no symptoms of cerebral hypoperfusion were elicited. CBF was unchanged after captopril administration, even in the patients showing a marked reduction in blood pressure. In the control group, the blood pressure, CBF and the cerebral metabolic rate for oxygen remained essentially constant following captopril administration. It is concluded that the cerebral circulation is well preserved during captopril treatment of chronic heart failure. This might be explained by a shift of the lower limit of CBF autoregulation towards lower blood pressure levels. PMID- 3089809 TI - Demonstration of neutrophil chemotactic activity in the sputum of cystic fibrosis patients with Pseudomonas aeruginosa infection. AB - The pathogenesis of tissue damage in the lungs of cystic fibrosis patients with chronic P. aeruginosa infection is quite complex and not well understood. Inflammatory cells, particularly neutrophils, are accumulated in the damaged tissues and in the sputum. This study demonstrates the presence of a heat-stable neutrophil chemotactic factor(s) in the sputum of CF patients. The chemotactic activity seems to be associated with the endotoxin present in the sputum. Chemotaxis of sol phase sputum was determined in a modified Boyden chamber assay. It was found that the sputum obtained from the patients showed strong chemotactic activity for peripheral blood neutrophils of normal individuals. The activity was greater than twice that of casein, a strong neutrophil chemo-attractant. Sputum at about dilution of 1:50 exhibited chemotactic activity equal to that of casein. Heat treatment of the sputum at 56 degrees C for 30 min, to inactivate complement, and at 100 degrees C for 15 min, to denature other proteins, somewhat reduced the chemotactic activity, but there was still strong chemotactic activity. The presence of endotoxin was demonstrated in both the non-heated and the heated samples by LAL and rocket immunoelectrophoresis. It is concluded that the sputum of CF patients contain chemotactic activity of heat-stable nature and most likely of bacterial origin endotoxin. These factors are involved in attraction of neutrophils to the lungs and sputum of these patients and contribute to the tissue damage of cystic fibrosis. PMID- 3089808 TI - Effect of obesity and weight reduction on biliary cholesterol saturation and the response to chenodeoxycholic acid. AB - Biliary cholesterol saturation indices (SI's) were measured in fasting duodenal bile from (i) obese and non-obese individuals with and without cholesterol gallstones, (ii) obese individuals undergoing weight reduction and (iii) obese gallstone patients receiving chenodeoxycholic acid (CDCA) therapy. Biliary lipid secretion rates were also measured in three obese subjects before and during 11 days starvation. The mean SI in fifteen non-obese controls (0.89 +/- SEM 0.06) was significantly lower than that in the twenty-four obese without (1.14 +/- 0.07; P less than 0.01), and in the twenty-nine non-obese with gallstones (1.30 +/- 0.05; P less than 0.001) while in sixteen obese gallstone patients, the mean SI of 1.55 +/- 0.06 was significantly higher than that seen in the other three groups (P less than 0.01-0.001). Although fifteen obese subjects lost 15% of their initial body weight during dieting, this did not change their SI's consistently. However in three obese individuals, total starvation did reduce the SI's and significantly lowered the biliary cholesterol secretion rate. Ten obese gallstone patients responded to 15.8 +/- 0.3 mg CDCA kg-1 day-1 by developing unsaturated fasting duodenal bile (SI 0.89 +/- 0.04). A further increase in CDCA dose to 19.0 +/- 0.7 mg kg-1 day-1, as a result of reducing body weight, was more effective in lowering SI's (0.75 +/- 0.06, range 0.51-1.0) than that achieved by increasing the dose to 18.9 +/- 0.46 mg kg-1 day-1 through more capsules per day (SI 0.89 +/- 0.03, range 0.67-1.25). These studies show that (i) biliary cholesterol SI's are greater when obesity and gallstones occur together than in either obesity or gallstones alone, and (ii) although weight loss in obese individuals does not consistently alter biliary cholesterol SI's, it may be beneficial in obese patients receiving CDCA therapy for gallstone dissolution. PMID- 3089810 TI - Lipoprotein modifications during dietary treatment in patients with primary type V hyperlipoproteinaemia. AB - Type V hyperlipoproteinaemia is a disorder of lipid transport characterized by the accumulation in serum of chylomicrons and very low density lipoproteins. The purpose of the study was the analysis of serum lipids and lipoproteins by ultracentrifugation in nine patients with primary type V hyperlipoproteinaemia before and during dietary treatment. After 30 days of balanced isocaloric diet mean serum triglycerides fell from 25.4 +/- 15.0 (mean +/- SD) to 2.8 +/- 1.7 mmol l-1. At the same time the chylomicrons and the very low density lipoproteins of flotation rate higher than 100 disappeared from the serum while the remaining very low density lipoproteins maintained unaltered their normal protein-lipid composition. After 30 days the low density lipoproteins increased significantly in concentration (from 1.6 +/- 0.8 to 4.1 +/- 1.1 mmol l-1 cholesterol) and their percentage content of cholesterol and triglyceride was increased and reduced, respectively. The highest concentration of intermediate density lipoprotein cholesterol was observed after 15 days of treatment (1.2 +/- 0.6 mmol l-1. The abnormally low concentrations and the physicochemical properties of the high density lipoproteins remained unchanged throughout the study (from 0.6 +/- 0.2 to 0.8 +/- 0.2 mmol l-1 cholesterol concentration) and no high density lipoproteins two (HDL2) were observed at any time. The effects of this treatment were an increase in low density and marginal change in high density lipoproteins which are considered, respectively, a positive and a negative risk factor for atherosclerosis. PMID- 3089811 TI - Bile acids and plasma high density lipoproteins: biliary lipid metabolism in fish eye disease. AB - Cholesterol in plasma high density lipoproteins (HDL) has been proposed to serve as preferential precursor for bile acid biosynthesis in the liver. Furthermore, a negative relationship between plasma levels of HDL cholesterol and biliary saturation with cholesterol has been reported in healthy females. We have performed metabolic studies on a female patient with fish eye disease, a familial condition where plasma HDL levels are reduced by 90% and the concentration of plasma triglycerides is moderately increased. Both the total production of bile acids and the net steroid 'balance' (reflecting total body cholesterol synthesis) were within the range seen in normolipidaemic as well as in hypertriglyceridaemic females. Also the biliary lipid composition and cholesterol saturation of bile were normal. A qualitative abnormality in the bile acid pattern was observed, however, in that the ratio between the synthesis of cholic acid and chenodeoxycholic acid was reduced. It is concluded that a low HDL cholesterol level is not necessarily associated with quantitative abnormalities of biliary lipid metabolism. The abnormal bile acid synthesis ratio may reflect changes in the hepatic precursor pools of cholesterol as the consequence of HDL deficiency, however. PMID- 3089813 TI - Haematological findings in chronic alcoholics after heavy drinking with special reference to haemolysis. AB - Haematological abnormalities are frequently found in heavy-drinking chronic alcoholics, but anaemia is generally a rare complication. When present, haemolysis is considered to be one of the most common causes. However, little is known about mild haemolysis without anaemia. The present report on eighteen male chronic alcoholics with a recent heavy debauche but without signs of severe liver disease gave support for the occurrence of a reversible low-degree haemolysis without concomitant gross changes of the erythrocytes. Thus the bone marrow showed an increased erythropoiesis in the absence of iron deficiency and known blood losses. Further, increased reticulocyte counts and low levels of haemopexin were noted in the early abstinence. Finally, during the withdrawal phase haptoglobin and haemopexin increased concomitantly with diminishing values of unconjugated bilirubin. The most likely cause of the proposed diminished red cell survival before the withdrawal is supposed to be a reduced membrane stability. PMID- 3089812 TI - Ursodeoxycholic acid treatment in humans: effects on plasma and biliary lipid metabolism with special reference to very low density lipoprotein triglyceride and bile acid kinetics. AB - Ursodeoxycholic acid reduces biliary saturation with cholesterol and may induce dissolution of cholesterol gallstones in man. In order to characterize the effects of this potentially useful bile acid on plasma lipid metabolism, we determined lipoprotein levels and very low density lipoprotein (VLDL) triglyceride kinetics in six hypertriglyceridaemic and three normolipidaemic subjects before and after 4-6 weeks of ursodeoxycholic acid treatment at a daily dose of 15 mg kg-1 body weight. The plasma levels of low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol were not significantly affected by therapy. Nor were the plasma level and apparent formation of VLDL triglycerides changed. In five subjects, the effects of a low dose (7.5 mg kg-1 body weight day-1 for 4-6 weeks) of ursodeoxycholic acid on biliary lipid composition and kinetics of cholic acid and chenodeoxycholic acid were determined. The relative concentration of cholesterol in bile was reduced to the same level as during treatment with a high dose of ursodeoxycholic acid. The synthesis rates of bile acids were not suppressed with ursodeoxycholic acid. It is concluded that, unlike chenodeoxycholic acid, ursodeoxycholic acid does not suppress endogenous bile acid production. The efficiency at lower doses, and the lack of effects on plasma lipid metabolism, may make ursodeoxycholic acid a more attractive alternative for clinical attempts of gallstone dissolution. PMID- 3089814 TI - Stable isotopes in clinical research. PMID- 3089815 TI - Glucoregulation in acute liver failure. AB - Five patients with fatal acute liver failure, given 5 g h-1 of glucose for the previous 12 h, were investigated by the hyper- and euglycaemic glucose 'clamp' technique, and the results compared with reported control values. Initial average blood glucose concentration was normal (6.0 mmol l-1, range 5.0-8.8). Plasma insulin and C-peptide concentrations were increased about tenfold (1450 pmol l-1, range 330-4021, and 3000 pmol l-1, range 670-7650, respectively). The whole body glucose metabolic rate was decreased to about half control values (21 mumol min-1 kg-1, range 6-28) and the insulin sensitivity of the glucose metabolism was decreased to about 15% (9.4 m3 min-1 kg-1, range 3.6-14.4). The calculated metabolic clearance of insulin was normal (520 ml min-1 (m2)-1, range 305-1027) and the calculated systemic delivery rate of insulin was about sixfold increased (1135 pmol min-1 (m2)-1, range 474-2010). The initial glucagon concentrations were fifty-fold increased (550 pmol 1, range 72-1309) and not suppressible by glucose and insulin. The patients thus exhibited pronounced insulin insensitivity and hyperinsulinaemia, attributable primarily to pancreatic hypersecretion. The reason for the relation between, and the pathogenetic importance of, these findings is not known. PMID- 3089816 TI - Representativity of regional to total bone mineral in healthy subjects and 'anticonvulsive treated' epileptic patients. Measurements by single and dual photon absorptiometry. AB - Dual photon (153Gd) and single photon (125I) absorptiometry were used to measure the regional bone mineral content (BMC) and density (BMD), as well as the total body mineral content (TBBM) and density (TBBD), in sixty-nine healthy subjects and in twenty-three epileptics on phenobarbitone. The BMCs (and BMDs) of all regions were significantly correlated to each other and to the TBBM (and TBBD). No difference in the ability to discriminate between the different study groups was found for the various regions, excepting the BMD of the head. The relationship between the forearm BMC and TBBM was highly significant, and identical in the five groups. The relationships between spinal BMC and forearm BMC, and TBBM differed in the five groups. It is concluded that some local measurement may be used as estimates of the total body bone mineral in some groups of patients with minor metabolic bone disease and healthy subjects. PMID- 3089817 TI - Circulating endogenous vasoactive intestinal polypeptide (VIP) in patients with uraemia and liver cirrhosis. AB - The concentration of vasoactive intestinal polypeptide (VIP) in peripheral venous plasma was median 6.0 pmol l-1 (range 0-20) in 112 normal subjects. In fifty three patients with decreased kidney function plasma VIP was significantly increased (median 15.0 pmol l-1, range 0.5-70, P less than 0.0001) and positively correlated to serum creatinine concentration (r = 0.51, P less than 0.001). In 133 patients with liver cirrhosis peripheral venous VIP was slightly elevated (median 7.0 pmol l-1 range 0-86, P less than 0.01). Samples obtained during a central venous catheterization showed significant renal extraction of circulating VIP in control subjects (median extraction fraction 23%, P less than 0.05, n = 6) and in patients with cirrhosis (median 60%, P less than 0.02, n = 8), but not in uraemic patients (median 0%, NS n = 5). In control subjects and patients with cirrhosis the concentration of VIP in the hepatic vein was significantly below that of systemic plasma (-42%, P less than 0.05, n = 6 and -45%, P less than 0.01, n = 10, respectively). On the contrary, in uraemic patients hepatic venous VIP was almost similar to systemic VIP (-4%, NS, n = 7). The results indicate that in normal subjects and patients with cirrhosis both the liver and kidneys are involved in the biodegradation of VIP. The elevated level of circulating VIP in uraemic patients may in part be due to decreased renal and hepatic biodegradation but increased neuronal release of VIP, especially in the splanchnic system, may also contribute to the increased plasma VIP in this condition. PMID- 3089818 TI - Intestinal permeability and lactose hydrolysis in human rotaviral gastroenteritis assessed simultaneously by non-invasive differential sugar permeation. AB - Changes in intestinal permeability and lactose hydrolysis have been investigated in three adults and fifteen infants with acute rotaviral gastroenteritis by differential sugar absorption. The method involves chromatographic measurement of urinary lactose, lactulose and L-rhamnose excretion following combined ingestion in an iso-osmolar test solution. All patients had abnormal intestinal permeability indicated by raised urine lactulose/L-rhamnose excretion, ratio of percentages recovered in 5 h, of 0.462 (0.100-1.227) mean and range, compared with 0.027 (0.008-0.052) for healthy controls (P less than 0.001). Ten patients also had urinary lactose/lactulose excretion ratios raised above the normal range (0.014-0.41, mean 0.258) during their acute illness, indicating impaired intestinal lactose hydrolysis. Both indices had become normal 4 weeks after the acute illness, serial investigation of five patients showing that improvement was complete much earlier. Except for the short duration these changes are similar to those associated with villous atrophy in coeliac disease. The test procedure was verified with respect to intestinal lactose hydrolysis by demonstrating a linear relationship between lactose/lactulose excretion and log jejunal mucosal lactase activity by in vitro assay (R2 = 0.95) in a further group of subjects. Differential lactose/lactulose/L-rhamnose absorption provides a non-invasive and sensitive index of small intestinal integrity of value for the interpretation of prolonged or otherwise complicated enteritis and the distinction of primary secondary intestinal lactase deficiency. PMID- 3089819 TI - Insulin receptor binding to monocytes and erythrocytes during normal human pregnancy. AB - In normal human pregnancy glucose tolerance deteriorates gradually in spite of a steady increase in plasma insulin levels. To see whether this change in insulin resistance is accompanied by changes in insulin receptor binding, insulin binding to monocytes and erythrocytes was measured serially during pregnancy and again post-partum in fifteen normal women. Insulin binding to monocytes increased from week 12 to week 24 of gestation (P less than 0.001) and it decreased from week 32 to week 36 (P less than 0.05). After delivery a new increase in insulin binding to monocytes was seen (P less than 0.05). Insulin binding to erythrocytes increased from week 30-32 to week 36 (P less than 0.05), decreased from week 36 to delivery (P less than 0.01) and decreased further post-partum (P less than 0.001). Insulin receptor binding was not significantly correlated to plasma insulin, estradiol, estriol, progesterone or cortisol. The insulin receptor binding to monocytes, but not to erythrocytes, paralleled the insulin resistance found in human pregnancy. PMID- 3089820 TI - Effect of prostacyclin on renal kallikrein release in man. AB - The aim of this research was to study exogenous prostacyclin effect on urinary kallikrein excretion (UKK) in man, to define whether prostacyclin-induced renin release and/or endogenously released cyclooxygenase products were responsible for prostacyclin-induced enhancement of UKK, to determine furosemide effect on UKK. Prostacyclin was infused in eight healthy men and repeated after propranolol and indomethacin treatment. Prostacyclin caused a dose-dependent increase of UKK. Pretreatment with propranolol and indomethacin did not affect prostacyclin induced enhancement of UKK, although it reduced absolute values of plasma renin activity. Furosemide increased UKK and simultaneously urinary 6-keto prostaglandin F1 alpha. We conclude that prostacyclin induces an increase in UKK in a dose-dependent manner; furosemide-induced renal prostacyclin synthesis is temporally related to enhancement of UKK; partial dissociation of UKK from plasma renin activity under propranolol and indomethacin treatment and in response to furosemide might suggest a direct effect of prostacyclin on UKK. PMID- 3089821 TI - Osteoporosis of the slender smoker revisited by epidemiologic approach. AB - A representative sample of 285 70-year-old Danish women were examined by case history, 125I photon absorptiometry of both forearms (BMC), and lateral X-rays of the spine. Fat mass was calculated from height (H), weight (W) and estimated lean body mass (LBM) as W-LBM/H kg m-1. Seventy-five participants with previous or present disease or treatment known to influence the calcium metabolism were excluded. The remaining 210 women included the final study groups of seventy seven long-term smokers and 103 non-smokers. Within both groups BMC correlated positively to fat mass, r = 0.447 and 0.560, respectively (P less than 0.001). The slopes of the regression lines and their positions were similar (P greater than 0.05). Hence, for a certain degree of overweight smoking per se does not influence BMC to a significant degree. Although the smokers were less obese (P less than 0.005) and tended to have lower BMC (P less than 0.10) their frequency of non-violent post-menopausal fractures, 40.3%, was the same as for non-smokers, 44.7%. The respective frequencies of definite osteoporotic fractures (i.e., spinal crush and fractures of the hip, proximal humerus and distal forearm) were comparable as well. In conclusion, the influence of smoking on the female skeleton seems mainly to be caused by the associated slenderness. PMID- 3089822 TI - Evidence for capillary leakage during chemotherapy in man. AB - The influence of intensive chemotherapy with high dose VP 16-213, cyclophosphamide and autologous bone marrow transplantation on transcapillary escape rate of albumin was evaluated. Transcapillary escape rate and plasma volume were measured with 131I-labelled albumin. Measurements were performed 1 day before (T0), 1 week after (T1) and 2 weeks after (T2) start of chemotherapy. Before therapy TER (n = 7, means = 7.1% h-1) was already raised in patients compared to controls (n = 5, means = 3.8% h-1, P less than 0.025). No difference was found for transcapillary escape rate on T1 (n = 9, means = 7.6% h-1) compared to T0. There was an increase of transcapillary escape rate from T0 to T2 (n = 8, means = 9.5% h-1, P less than 0.05). Plasma volume did not change during therapy. Serum albumin concentrations were reduced before chemotherapy (means = 38 g 1(-1] compared to controls (means = 44 g l(-1]. After 1 (means = 34 g 1(-1] and 2 weeks (means = 31 g 1(-1] these concentrations decreased further. The same was found for intravascular mass of albumin related to body weight. The intravascular mass of albumin/bodyweight and the transcapillary escape rate are related in the patients (r = -0.477, P less than 0.01) and the patients plus controls (r = 0.585, P less than 0.001). This means the higher the transcapillary escape rate the lower the intravascular mass of albumin. No correlation between transcapillary escape rate and presence of fever was found. It can be concluded that intensive chemotherapy leads to further increase of an already elevated transcapillary escape rate for albumin. PMID- 3089823 TI - Effects of indomethacin, prostaglandins E2 and I2 on the tone of human isolated femoral arteries. AB - Strips of endothelium-denuded femoral arteries from operated patients were set up for isometric recording. Indomethacin (IND, 3 mumol 1(-1] enhanced basal tension of the arteries from 0.13 +/- 0.04 to 0.86 +/- 0.12 mN (P less than 0.001; n = 16) and potentiated the contractile responses of the strips to noradrenaline (NA); EC50 for NA was 1.5 +/- 0.3 mumol 1(-1) (n = 6) in the absence, and 0.4 +/- 0.07 mumol 1(-1) (n = 6) in the presence of IND (P less than 0.01). PGI2 produced dose-related relaxation in IND-treated vessels, its IC50 being 15.0 +/- 1.3 nmol 1(-1). Low concentrations of PGE2 (0.85-8.5 nmol 1(-1] reduced whereas its higher concentrations (28-85 nmol 1(-1] increased smooth muscle tone in the presence of IND. These results indicate that human femoral arteries--unlike femoral arteries of some laboratory animals--are highly sensitive to cyclooxygenase inhibition as well as to PGI2 and PGE2. PMID- 3089824 TI - Serotonin increases the velocity of propagation and frequency of the migrating myoelectric complexes. AB - The effect of serotonin on the myoelectric activity of the gastrointestinal tract was evaluated in seven opossums. Continuous intravenous administration of serotonin reduced the cycle duration of the migrating myoelectric complex and increased the velocity of propagation of the phase III. These changes were dose dependent and were observed only with high doses of serotonin of 0.1 mg kg-1 h-1 or more. Infusion of 0.01 mg kd-1 h-1 had no effect on the motility of the gastrointestinal tract. The motility changes occurred in all segments of the gastrointestinal tract studied and were characterized by a continuous and organized increase in the velocity of propagation of the activity front (phase III) of the migrating myoelectric complex from the antrum to the terminal ileum. The cycle duration of the two migrating myoelectric complexes following administration of methysergide at 1.0 mg kg-1 was similar to the control migrating myoelectric complexes. We concluded that continuous infusion of serotonin in the opossum increases the velocity of propagation of the phase III of the migrating myoelectric complex from the antrum to the terminal ileum. PMID- 3089825 TI - Diazepam-induced decrease in histamine turnover in mouse brain. AB - The effect of diazepam on brain histamine turnover was examined in mice. The steady state levels of histamine and tele-methylhistamine remained unchanged following the i.p. administration of 0.2-20 mg/kg of diazepam. However, diazepam in doses over 5 mg/kg significantly decreased histamine turnover, as estimated from the accumulation of tele-methylhistamine after pargyline treatment. Other benzodiazepines such as chlordiazepoxide, nitrazepam and estazolam in high doses also decreased histamine turnover. The inhibitory effect of diazepam on histamine turnover was antagonized by the pretreatment with a benzodiazepine antagonist Ro 15-1788. The histamine turnover was significantly inhibited by 2 mg/kg of muscimol. Diazepam (0.2-1 mg/kg) markedly and dose-dependently potentiated the inhibitory effect of 1 mg/kg of muscimol from non-significant to highly significant levels. The potentiation by diazepam was also antagonized by Ro 15 1788. Therefore, diazepam probably decreases histamine turnover in the brain via the benzodiazepine-GABA receptor complex. PMID- 3089826 TI - Effects of Iskedyl and its two constituents raubasine and dihydroergocristine on the release of [3H]noradrenaline and [3H]serotonin in canine basilar arteries. AB - In strips of isolated canine basilar arteries, previously labeled with 3 X 10(-7) M of either [3H]noradrenaline or [3H]serotonin, three consecutive periods of electrical stimulation (2 Hz) evoked a reproducible overflow of the respective [3H]amine. Increasing concentrations of raubasine (7.5 X 10(-7)-7.5 X 10(-6) M) did not influence the spontaneous 3H efflux but increased the stimulation-induced 3H overflow in a concentration-dependent way. The highest concentration of raubasine used (2.5 X 10(-5) M) caused an increased spontaneous 3H efflux but no longer augmented the stimulation-induced 3H overflow. Dihydroergocristine (5.4 X 10(-8)-1.8 X 10(-6) M) did not affect the spontaneous 3H efflux; the compound slightly but significantly reduced the stimulation-evoked 3H overflow concentration dependently. High concentrations of Iskedyl (mixtures of raubasine and dihydroergocristine in a 14:1 molar ratio) augmented the spontaneous 3H efflux and moderately decreased the stimulation-induced 3H overflow. Although some quantitative differences were noted, the compounds exerted similar effects on arteries labeled with either [3H]noradrenaline or [3H]serotonin. The most important difference detected was that DHEC decreased the stimulation-induced release of [3H]serotonin more than that of [3H]noradrenaline. Our results allow a comparison of [3H]noradrenaline and [3H]serotonin release in the dog basilar artery: the basal fractional release of [3H]serotonin was higher than that of [3H]noradrenaline while the stimulation-induced overflow was equal in both groups of tissues. The constituents of Iskedyl can profoundly affect the release of the neurotransmitters. Raubasine, a presynaptic alpha-receptor antagonist, increases the stimulation-induced release of the neurotransmitters and both DHEC, a presynaptic receptor agonist, and the combination of the compounds, Iskedyl, decrease the release of the neurotransmitters. PMID- 3089827 TI - Research update: report on retinitis pigmentosa and the immune system workshop 7 8 November 1985. PMID- 3089828 TI - Developmental changes in membrane protein expression by chick lens cells in vivo and in vitro and the detection of main intrinsic polypeptide (MIP). AB - We have compared the long-term developmental changes in water-insoluble protein expression by chick lens cells in vitro and in vivo. Crude membrane fractions were prepared by alkali treatment of the urea-insoluble protein fraction, and the proteins analysed by sodium dodecyl sulphate-polyacrylamide (SDS-PAGE) gel electrophoresis. The major component present in the urea-insoluble fraction of chick lens fibres, a 25,000 MW polypeptide (MIP-25K) was more abundant in adult (8 weeks) than day-old post-hatch chick lens fibre masses. MIP-25K was detected in differentiated but not predifferentiated lens cell cultures, and indirect immunofluorescence using anti-bovine MIP antiserum indicated that MIP-25K was localized in the lentoid bodies. Our findings indicate that the urea-insoluble protein profiles of long-term well-differentiated chick lens cell cultures are qualitatively very similar to the profiles of the lens fibres. The data also confirm that the expression of MIP-25K, rather than the expression of water soluble crystallin protein, is a marker for lens cell differentiation, and confirm earlier reports, which have been disputed, that delta-crystallin (but not alpha-or beta-crystallin) is specifically associated with chick lens fibre membranes. PMID- 3089829 TI - Modulation of corneal lipoxygenase by ascorbic acid. AB - We have examined the influence of ascorbic acid on the generation of lipoxygenase products by the rabbit cornea, an avascular tissue which is continuously bathed by high concentrations of ascorbic acid present within the aqueous humor of the eye. Corneal homogenates were incubated with [14C]arachidonic acid and the resulting metabolites separated by thin-layer chromatography. The metabolites were then quantified by liquid scintillation counting techniques. The biosynthesis of the major lipoxygenase product formed by the cornea, 12-HETE, was significantly inhibited by physiological concentrations of ascorbic acid; PGE2 formation by the cornea was not altered in the presence of ascorbic acid. Furthermore, ascorbic acid inhibited the formation of 12-HETE in the presence of catalase, indicating that hydrogen peroxide generated by ascorbate was not responsible for diminishing the lipoxygenase activity of the cornea. However, high concentrations of hydrogen peroxide (10(-4) M) did inhibit the formation of 12-HETE by the corneal homogenates. Another antioxidant, 2,6-dichlorophenol indophenol (10 micrograms ml-1), also inhibited the formation of 12-HETE by the cornea. Therefore, it appears that the inhibition of corneal lipoxygenase by ascorbic acid could be related to the antioxidant properties of this vitamin. These studies suggest that ascorbic acid within the aqueous humor might modulate lipoxygenase activity within the cornea. PMID- 3089830 TI - Hematopoietic colony formation after allogeneic bone marrow transplantation: enhancement by cyclosporin A and anti-gamma-(immune) interferon antiserum in vitro. AB - Bone marrow hematopoietic progenitors (CFU-GM, CFU-E, and BFU-E) were found to be markedly decreased in 21 bone marrow transplant recipients studied from one to 51 months after transplantation. In these patients, bone marrow colony formation could be significantly enhanced by in vitro incubation of the bone marrow target with cyclosporin A (CyA; 0.5 microgram/ml) or with a monoclonal anti-gamma (immune) interferon (IFN-gamma) antibody. Both effects were highly correlated. The data indicate that (a) endogenous elaboration of IFN-gamma may contribute to decreased colony formation in allogeneic bone marrow transplant recipients, and (b) CyA may induce a gradual release of the progenitor cell pool from IFN-gamma mediated suppression. PMID- 3089831 TI - Curvature detection in the visual field and a possible physiological correlate. AB - Discrimination of curvature in nearly straight stimuli was measured for twelve stimulus orientations, corresponding to the hours of the clock, at eleven positions in the visual field of human observers. Displacements below the diameter of a photoreceptor can be detected foveally. In the periphery of the visual field, stimuli oriented towards the fovea yield best results. This anisotropy of orientation discrimination seems not to have an optical cause. It has a close correlation both to the structure and functional properties of cat ganglion cells, to the organization of receptive fields in area 17 and to the geometry of ocular dominance stripes. PMID- 3089832 TI - Is amygdala kindling in rats a model for drug-resistant partial epilepsy? AB - Amygdala-kindled female rats were used to compare the effects of seven antiepileptic drugs that are clinically used for treatment of partial epilepsy with complex symptomatology, on generalized seizures, focal seizures, or electrographic seizure activity at the focus. As a second approach of drug evaluation, drug effects on mean latency, severity, and duration of the seizures were determined. Anticonvulsant potencies obtained were compared with those determined in the maximal electroshock seizure test in female rats. Phenobarbital, phenytoin, carbamazepine, valproic acid, diazepam, clonazepam, but not primidone dose-dependently suppressed generalized motor seizures in kindled rats; however, except for the benzodiazepines, ED50S were substantially higher than those determined in the maximal electroshock seizure test. Compared with their effect on generalized motor seizures, all drugs were much less potent in blocking focal seizures and afterdischarges recorded from the amygdala. The data suggest that with respect to behavioral and pharmacologic characteristics of the amygdala kindling model, fully kindled rats may be a useful model for drug resistant complex partial seizures with secondary generalization. Results of experiments with novel inhibitors of GABA uptake, which were inactive in the maximal electroshock seizure test but highly potent against kindled seizures, suggest that such drugs might be more effective than current antiepileptic drugs for treatment of partial epilepsy. PMID- 3089833 TI - Effect of cervical spinal cord hemisection and hemidiaphragm paralysis on arterial blood gases, pH, and respiratory rate in the adult rat. AB - We documented the changes that occur in arterial blood gases, pH, and respiratory rate in rats subjected to a C2 spinal cord hemisection which results in paralysis of the ipsilateral hemidiaphragm. The results indicated that rats compensate for hemidiaphragm paralysis by maintaining arterial pO2 through an increased rate of respiration. This observation is of interest because it implies a form of functional recovery from spinal cord injury which has heretofore not been demonstrated. PMID- 3089834 TI - Regional pattern and heat-resistance of brain 5'-deoxy-5'-methylthioadenosine phosphorylase. AB - The distribution of 5'-deoxy-5'-methylthioadenosine (MTA) phosphorylase in 10 pig brain areas was determined. The observed regional differences of the enzymatic activity seem to reflect more the pattern of brain spermine distribution rather than that of spermidine. Moreover, comparative studies on the heat-resistance of MTA phosphorylase extracted from the whole brain of various species suggest structural differences in the enzyme molecules occurring in the brains of different animals. PMID- 3089835 TI - Amino-aromatic interactions in proteins. AB - Geometric analysis of 33 refined high-resolution protein crystal structures (2 A or higher) demonstrates that side-chain amino groups interact with aromatic side chains. Positively charged or delta(+) amino groups of lysine, arginine, asparagine, glutamine and histidine are preferentially located within 6 A of the ring centroids of phenylalanine, tyrosine and tryptophan, where they make van der Waals' contact with the delta(-) pi-electrons and avoid the delta(+) ring edge. This geometric pattern is different from the distribution expected due to random close packing of side chains in a protein. It is opposite to oxygen- and sulfur aromatic interactions, similar to aromatic-aromatic interactions, and almost certainly electrostatic in origin. PMID- 3089836 TI - High homology is present in the primary structures between murine senile amyloid protein (ASSAM) and human apolipoprotein A-II. AB - The primary structure of a murine senile amyloid protein (ASSAM) was determined. The protein consists of a single polypeptide chain of 78 amino acid residues. The amino-terminus is blocked with pyrrolidone-carboxylic acid. The sequence differs from that of the known murine amyloid A protein and is highly homologous to human apolipoprotein (apo) A-II. The result indicates that the putative precursor of the senile amyloid protein is apo A-II in mice. PMID- 3089837 TI - Requirement of monohydroperoxy fatty acids for the oxygenation of 15LS-HETE by reticulocyte lipoxygenase. AB - The lipoxygenase from reticulocytes oxygenates 15LS-HETE to 8-hydroperoxy-15 hydroxy-5,9,11,13-eicosatetraenoic acid and 5-hydroperoxy-15-hydroxy-6,8,11,13 eicosatetraenoic acid only in the presence of catalytic concentrations of monohydroperoxy fatty acids. During this reaction the hydroperoxy fatty acids are converted to more polar products including hydroxy fatty acids. From kinetic measurements of 15LS-HETE oxygenation it was calculated that 1 mol monohydroperoxy fatty acid is consumed during the oxygenation of about 9 mol 15LS HETE. PMID- 3089838 TI - Tumour promotor 12-O-tetradecanoylphorbol 13-acetate inhibits angiotensin II induced inositol phosphate production and cytosolic Ca2+ rise in rat renal mesangial cells. AB - Preincubation of rat renal mesangial cells with 12-O-tetradecanoylphorbol 13 acetate (TPA) strongly inhibited the increases of inositol phosphates and of free cytosolic Ca2+ induced by angiotensin II (10(-7) M). TPA had no significant effect on the basal values of inositol phosphates and of free cytosolic Ca2+. Inhibition appeared already after 1 min and was maximal after 5 min. These effects occur without significant changes on angiotensin II binding in intact cells. The concentration of TPA needed (10(-9)-10(-7) M) was in the range believed to cause specifically an activation of protein kinase C. Furthermore the biologically inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate was without effect. From the entirety of these results it is likely that protein kinase C inhibits angiotensin II activation of phospholipase C at a stage distal to receptor occupancy. PMID- 3089839 TI - A deazaadenosine-insensitive methylation of phosphatidylethanolamine is involved in lipoprotein secretion. AB - We have examined the effect of inhibitors of methylation of phosphatidylethanolamine on lipoprotein secretion from cultured rat hepatocytes. The incorporation of [1-3H]ethanolamine into phosphatidylcholine of hepatocytes and secreted lipoproteins was inhibited by greater than 90% by the methylation inhibitors 3-deazaadenosine and Neplanocin. In addition, these compounds strongly inhibited the incorporation of [3-3H]serine into the choline moiety of phosphatidylcholine of the hepatocytes, but had no effect on incorporation of [3 3H]serine into secreted phosphatidylcholine. The results suggest that a pool of phosphatidylcholine targeted for lipoprotein secretion originates from phosphatidylethanolamine made from serine and this methylation reaction has the unique property of being insensitive to 3-deazaadenosine. PMID- 3089840 TI - Chilling followed by incubation at 37 degrees C causes a reduction in NAD+ levels which can be prevented by the poly(ADP-ribose)transferase inhibitor 3 aminobenzamide. AB - The exposure of cells for 60 min to a serum free medium at ice temperature followed by a return to normal culture conditions (30 min at 37 degrees C) caused a dramatic decrease in NAD+ levels. This decrease in NAD+ was prevented by 3 aminobenzamide. Alkaline elution analysis of DNA from cultures that were sisters to the ones utilized for measuring cellular NAD+ content revealed an absence of DNA breakage. These data suggest that poly(ADP-ribose)transferase may be induced in conditions not involving DNA fragmentation. The induction of this enzyme could therefore represent a cellular emergency reaction and not just a response to DNA damage. PMID- 3089842 TI - Daily follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in ten women harboring uterine leiomyomas. AB - Serum follicle-stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were assessed every day in ten women harboring uterine leiomyomas during a complete menstrual cycle. Total area under the curve was individually calculated for E2 and P. The results obtained in this group were then compared with those obtained in a control population. No statistical difference was found. We concluded that patients harboring uterine leiomyomas had, in this study, a normal menstrual cycle. The role of estrogens in the physiopathology of uterine leiomyoma was not related to abnormally high levels of serum E2 or abnormally low levels of P. PMID- 3089841 TI - The importance of hydroperoxide activation for the detection and assay of mammalian 5-lipoxygenase. AB - Sulfhydryl reagents such as dithiothreitol stabilized human leukocyte 5 lipoxygenase (5-LO) during purification. During enzyme assay, however, these reagents led to irreproducible or unexpectedly low activity. This inconsistency in the assay was eliminated by inclusion of hydroperoxyeicosatetraenoic acids (1 5 microM) during the reaction which effected a 10-20-fold stimulation of 5-LO activity. Structural studies indicated that an intact hydroperoxy function, and a long-chain fatty acyl moiety were required for 5-LO stimulation. These data suggest that human leukocyte 5-LO is activated by hydroperoxy fatty acids, and that this results in a requirement for exogenous hydroperoxide in the presence of sulfhydryl reagents. PMID- 3089843 TI - Pregnancy after combined treatment with bromocriptine and tamoxifen in two patients with pituitary prolactinomas. AB - Two patients with prolactinomas who could not tolerate a large dose of bromocriptine were treated with combination of bromocriptine and tamoxifen. This combined therapy normalized the PRL level and restored a regular ovulatory cycle, which resulted in pregnancy. PMID- 3089844 TI - Comparison of the effects of follicle-stimulating hormone and human menopausal gonadotropin on peripheral serum and follicular fluid hormones during ovarian stimulation. PMID- 3089845 TI - Menometrorrhagia, infertility, elevated serum estradiol, and hyperprolactinemia resulting from increased aromatase activity (MIEHA syndrome). PMID- 3089846 TI - Absence of predictive value of follicular inhibin on the results of human in vitro fertilization. AB - During the periovulatory period, inhibin did not have a discriminant role in oocyte fertilizability. A possible role in the gonadotropin surge was not revealed by analysis at the time of follicular rupture. Furthermore, inhibin activity appears to be very low. But inhibin could still have an effect upon growth and atresia of the follicles of the following cycles. PMID- 3089847 TI - [Various routes of L-tryptophan transport in the small intestine of the chick]. AB - Presence of two mechanisms in the accumulation of L-tryptophan by the mucosal cells of chicken small intestine was determined in vitro: sodium-independent and sodium-dependent those, the latter being of a major importance. Analysis of the accumulation kinetics in the linear stage showed that at the replacement of sodium with potassium ions in the incubation medium, a decrease of Kt (from 4.44 mM to 1.05 mM) as well as V (from 0.78 mM/min/cm to 0.12 mM/min/cm) occurs. High level of L-threonine, L-alpha-alanine, L-valine (100 mM) considerably inhibit the accumulation of L-tryptophan from 0.24 or 2.40 mM solution, the highest inhibition (78-96%) being related to the sodium-dependent transport mechanism. No considerable changes in Kt (4.0 mM) were observed in the saturated stage of transport whereas V showed a rapid decrease (0.22 mM/min/cm). Adding of modifier 0.64 mM L-alpha-alanine was followed by the increase both in Kt (5.71 mM) and V (0.37 mM/min/cm). PMID- 3089848 TI - [Studies on prolactin secreting capacity in the ovulatory infertile patients with transient hyperprolactinemia]. AB - The changes in serum prolactin levels during the menstrual cycle have not been clarified yet. The present study was conducted to investigate whether the changes in serum prolactin levels during the menstrual cycle exist in ovulatory infertile patients having high prolactin release due to TRH administration described below (transient hyperprolactinemia) and control cases. Serum prolactin levels in both groups were less than 25 ng/ml at daytime. In the patients with transient hyperprolactinemia, serum prolactin levels showed more than 150 ng/ml at 30 min. after the administration of 500 micrograms of TRH, and those were less than 150 ng/ml in the normal control group. The daily changes of serum FSH, LH, prolactin, estradiol and progesterone levels were determined by radioimmunoassay in 6 cases of transient hyperprolactinemia and 5 controls which showed normal ovulatory cycles in the patterns of the BBT charts and other hormones. An estrogen feedback test was also carried out at the mid-luteal phase in 9 cases of transient hyperprolactinemia and the controls to determine serum levels of FSH, LH, prolactin and estradiol. In the patients with transient hyperprolactinemia, 5 mg of bromocriptine was administered every day for more than 30 days, and the effects of bromocriptine on the changes in serum gonadotropin levels by the estrogen feedback test were also analysed. Serum prolactin levels in the follicular, ovulatory and mid-luteal phases increased significantly in the patients with transient hyperprolactinemia, compared to the controls (p less than 0.005). The pattern of serum prolactin levels in the patients with transient hyperprolactinemia was almost synchronized with that of serum estradiol levels. There was also a significant correlation (r = 0.5782, p less than 0.005) between the prolactin and estradiol levels in the serum of the patients. The obvious change was not noted in serum prolactin levels during the menstrual cycle of the controls. No significant change in other hormones was observed during the cycle between these two groups. After the administration of estradiol benzoate (100 micrograms/kg), serum estradiol levels increased markedly, serum prolactin levels increased with the similar change in serum estradiol levels, and serum prolactin levels in the patients with transient hyperprolactinemia were significantly higher compared to those of the controls (p less than 0.01 approximately 0.005). The responses of serum gonadotropin levels by the administration of estradiol benzoate had good positive and negative feedback effects in the patients with transient hyperprolactinemia as well as those of the control group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3089849 TI - Diseases associated with psoriasis in a general population of 159,200 middle aged, urban, native Swedes. AB - A defined general population of 159,200 male and female native Swedes born in the period of 1911-1940, from an urban catchment area of the then only general hospital, was followed over a decade (1970-1979) with regard to inpatient hospitalization for all kinds of diagnoses. Psoriasis cases (n = 372) are significantly (p less than 0.001) associated with a spectrum of diseases: male as well as female psoriatics seem to show excess rates of viral infections, alcoholism, hypertension, pneumonia, liver cirrhosis, urticaria, and rheumatoid arthritis. Psoriasis in males only seem to be associated with iritis and ankylosing spondylitis, whereas psoriasis in females only is associated with lung cancer, diabetes, obesity, myocardial infarction and asthma. PMID- 3089850 TI - Oral gold therapy (Auranofin) in pemphigus vulgaris. AB - Auranofin (AF), an oral gold salt, was given for 9-18 months to 3 patients with pemphigus vulgaris. There was a slight improvement with significant oral pain relief in 2, and a complete remission in 1. Two patients including the one with the remission, subsequently flared up under AF therapy. Although AF is said to be better tolerated than parenteral gold this limited series suggests that it does not seem to have a superior therapeutic effect in PV. PMID- 3089851 TI - Time-resolved structural studies on catalysis in the crystal with glycogen phosphorylase b. PMID- 3089852 TI - The vitelline envelope to fertilization envelope conversion in eggs of Xenopus laevis. AB - Fertilization of the Xenopus laevis egg causes the conversion of the vitelline envelope to the fertilization envelope, a change reflected in the loss of sperm penetrability of the egg and the appearance of an electron-dense layer on the outer aspect of the fertilization envelope. As seen by one-dimensional gel electrophoresis, two components with molecular weights of 69,000 and 64,000 in the vitelline envelope were converted to 66,000 and 61,000 in the fertilization envelope. By two-dimensional gel electrophoresis, the components in the 69,000 and 64,000 molecular weight regions of the vitelline envelope were seen to shift to more basic isoelectric points upon conversion to the fertilization envelope. Peptide mapping by limited proteolysis suggested that the 69,000 and 64,000 molecular weight components shared the same polypeptide chains but the smaller glycoprotein lacked a carbohydrate side chain found on the larger species. Similar sites on each glycoprotein were affected when the vitelline envelope was converted to the fertilization envelope. No N-terminal amino acids could be identified on the envelope components, indicating that these glycoproteins have blocked N-termini. Ionophore A23187-activation of jellied eggs (but not dejellied eggs) caused the molecular weight changes in the absence of sperm. Thus, factors from the jelly and the cortical granules but not from sperm apparently are involved in the processing of the 69,000 and 64,000 molecular weight components. PMID- 3089853 TI - Transferrin and the trophic effect of neural tissue on amphibian limb regeneration blastemas. AB - Nerves promote regeneration of amputated urodele limbs, but the chemical basis of the effect is not known. We have examined the possible involvement of the iron transport factor transferrin, which is important for cell proliferation and is present in vertebrate nervous tissue. Newt brain extract stimulated incorporation of [3H]thymidine in cultured blastemas from regenerating newt forelimbs, showing a biphasic dose-response similar to that of heterologous transferrin. As shown previously for transferrin, the inhibitory effect of brain extract at high concentrations was relieved by the addition of iron. Activity of brain extract was reduced by treatment with an iron-chelating agent and fully restored by the readdition of iron. Double immunodiffusion of newt tissue extracts and antibodies against newt plasma transferrin demonstrated the presence of transferrin-like factors in brain, spinal cord, and peripheral nerve. These results indicate that activity of transferrin may be part of the trophic effect of brain extract on cultured blastemas. PMID- 3089854 TI - Persistence of mullerian ducts in male rabbits passively immunized against bovine anti-mullerian hormone during fetal life. AB - A female rabbit was immunized against purified bovine AMH and mated. Booster injections were given at Day 8 of pregnancy to ensure a high titer of anti-AMH antibodies at the time the rabbit fetal testis begins to produce AMH. In three consecutive litters, the immunized female produced a total of 12 males, 9 of which had persistent Mullerian duct derivatives. No other significant abnormalities were detected in these animals, which were compared to the offspring of a control saline-injected female. In particular, testicular morphology was normal in most animals, and serum FSH levels did not differ from controls. This experimental model lends no support to the hypothesis that AMH controls extra-Mullerian events of male sex differentiation, nor that of the existence of a regulatory mechanism for synthesis of AMH by Sertoli cells, but it does not definitely exclude these possibilities, inasmuch as our tentative conclusions are based upon study of only one immunized female. PMID- 3089855 TI - Regulation of synthesis of larval serum proteins after transplantation of larval fat body into adult Drosophila melanogaster. AB - The larval serum proteins, LSP1 and LSP2, of Drosophila melanogaster are synthesized by the fat body during the third instar. We examined the potential for LSP synthesis by fat body implants in adult flies. Fat body from third instar donors will continue to synthesize LSPs in both males and females. Implants from late second instar larvae will start synthesizing LSP1 and LSP2 in females but only LSP1 in males, suggesting that regulation of these proteins is not the same and that the physiological milieu in the two sexes differs. The newly synthesized LSPs are secreted into the hemolymph for approximately 48 hr when secretion stops but synthesis continues. This sequence follows the pattern for LSP secretion in situ. Fat body from mid second instar larvae is variable in its ability to synthesize LSPs. LSPs are not detected in implants from first instar larvae despite there being a high level of protein synthesis in the implant and considerable growth of the fat body cells. We conclude that there is a critical stage of differentiation during the latter half of the second instar when the fat body becomes independent of the larval milieu and can synthesize LSPs in the adult. PMID- 3089856 TI - Encapsulation of rat islets of Langerhans prolongs xenograft survival in diabetic mice. AB - Rat islets encapsulated in alginate-polylysine membranes were implanted intraperitoneally into nonimmunosuppressed streptozocin-induced diabetic mice. Diabetes was reversed within 3 days, and the animals remained normoglycemic for up to 144 days, with a mean xenograft survival of 80 days. This was significantly greater than nonencapsulated islets, which functioned for less than 14 days. The graft survival rate at 50 days was greater than 80%. Xenografts of rat islets encapsulated in alginate-polyornithine membranes also had a prolonged survival rate. This study demonstrates that encapsulation of pancreatic islets in semipermeable membranes can prolong xenograft survival in the absence of immunosuppression. PMID- 3089857 TI - Workload measurement system analyses out-patient costs. AB - The in-patient and one-day-care analyses focus on hospital patients and patient categories and the impact of these categories on each department and on the hospital, whereas the out-patient analyses use the requesting clinical service as the patient category. The approach taken to the analyses of out-patient workload is much simpler that the approach to the categorization and analysis of in patient and one-day-care stays. The simpler approach to the analysis of out patient services provides meaningful yet easy-to-use information for a relatively low investment of time and effort. Future endeavors to analyse the costs of out patient services should link together all visits to hospital departments associated with a particular "out-patient case" (which may take place over several days). To accommodate such analyses of hospital out-patient products, complete hospital out-patient products (that is, categories of cases) that are more analogous to in-patient categories must be defined. PMID- 3089859 TI - The influence of recombinant DNA-derived human and murine gamma interferons on mouse hepatic drug metabolism. AB - Human gamma interferon given for up to 5 days by subcutaneous infusion or intraperitoneal injection did not significantly alter mouse hepatic microsomal oxidative drug-metabolizing enzyme activities. In contrast, murine gamma interferon and human alpha interferon given for 5 days at the same dose (10(7) units/kg) caused 25 and 50% decreases, respectively, in hepatic microsomal cytochrome P-450 concentrations. The human alpha interferon-induced decline in cytochrome P-450 was accompanied by a significant drop in p-nitroanisole demethylase activity and significant elevations in serum alanine aminotransferase and cytosolic glutathione S-transferase activities. An elevation in glutathione-S transferase was the only significant change found following human gamma interferon administration. Microsomal UDP-glucuronosyltransferase activity was unaffected by any interferon. PMID- 3089858 TI - Glycosaminoglycans and proteoglycans synthesized by rat limb buds during prechondrogenic and chondrogenic stages. AB - The sulfated glycosaminoglycans synthesized in the forelimb plates of rats on days 12, 13, 14, and 15 of gestation were characterized by their susceptibility to various glycosaminoglycan lyases. On days 12 and 13, heparan sulfate accounted for approximately 65% of the newly synthesized sulfated glycosaminoglycans. Small amounts of dermatan sulfate and chondroitin sulfates were also observed. On day 14, the relative amount of chondroitin 4-sulfate began to increase, there being a compensatory decrease in the amount of heparan sulfate. 35S-Sulfate-labeled material was extracted from day-13 forelimb plates with 4 M guanidine/HCl without proteolysis. Using ultracentrifugation on a sucrose density gradient, the extract was separated into two peaks: a light peak (L) mainly composed of heparan sulfate, and a faster-sedimenting peak (M) mainly composed of chondroitin sulfate. The cartilage-type proteoglycan (H) was first detectable on day 14 of gestation, indicating that chondrogenesis in rat forelimb plates starts on day 14 of gestation. In addition to these previously identified glycosaminoglycans or proteoglycans, we isolated an unknown component in the glycosaminoglycan preparations obtained from limb plates during these developmental stages. This component was not found in glycosaminoglycan preparations obtained either from the brain or tail of rat fetuses at the same stages. PMID- 3089860 TI - The induction profile of three orally active imidazopyridine-containing cardiotonic agents in rat hepatic microsomes. AB - The induction of hepatic cytochrome P-450-linked monooxygenases has been studied after the twice daily, oral administration of two imidazo[4,5-c]pyridine containing compounds and one imidazo[4,5-b]pyridine-containing drug. The compounds were administered by the oral route, at different doses, for 6 days after which time hepatic microsomes were prepared. In vitro biochemical assays revealed that all three compounds increased the O-deethylation of 7 ethoxyresorufin in a dose-dependent manner while not significantly affecting either the O-dealkylation of 7-ethoxycoumarin or the levels of NADPH-cytochrome c reductase. Ethylmorphine N-demethylation was decreased after dosing with the imidazo[4,5-b]pyridine-containing drug. Levels of cytochrome(s) P-450 and liver to-body weight ratios were not significantly altered. The imidazo[4,5-b]pyridine containing compound was more potent in terms of the induction of 7 ethoxyresorufin than either of the imidazo[4,5-c]pyridine-containing compounds but was approximately fourfold less active in this regard than 3 methylcholanthrene. No induction of cytochrome-P-450-linked monooxygenase activities was evident at a twice daily dose of 5 mg/kg for 6 days for all three compounds tested, constituting a no-effect level. The imidazo[4,5-c]pyridine containing compounds exhibited modified Type II difference spectra when added to a suspension of rat hepatic microsomes. The imidazo[4,5-b]pyridine-containing compound has previously been reported to be a rapid and potent inducer of monooxygenase activity and have a Type II difference spectrum. PMID- 3089861 TI - Acute inhalation toxicopathology of lithium combustion aerosols in rats. AB - Male and female F344/Lov rats were exposed to aerosols produced by burning lithium metal under conditions designed to stimulate a fire in the containment building of a fusion reactor. Lithium combustion aerosols were generated by sweeping lithium vapor into air atmospheres with controlled CO2 and H2O concentrations. Chemical analyses of the aerosols produced indicated a dependence of the chemical form of carbon dioxide concentrations and relative humidity. Under conditions of low CO2 concentration and low relative humidity (less than 25%), the aerosol was predominantly lithium monoxide with some lithium hydroxide and about 12% lithium carbonate. Under conditions of high relative humidity (greater than 75%), the aerosol was primarily lithium hydroxide with about 23% lithium carbonate. Although these two aerosols might be expected to have different acute toxicities based on their differing alkalinities, the 14-day LC50 values (with 95% confidence limits) determined after 4-hr exposures were 940 (730 1200) mg/m3 for the lithium oxide and hydroxide mixture and 960 (830-1200) mg/m3 for the lithium hydroxide aerosols. Histopathologic lesions were observed in the nasal turbinates, larynx, and occasionally in the lungs with both aerosols. The most prominent lesions were necrotizing laryngitis and ulcerative rhinitis. Pulmonary lesions represented a secondary extension of the upper respiratory tract lesions rather than a primary manifestation of lithium toxicity. The similarities in the LC50 values and also in the histopathologic lesions observed suggest that any Li2O in the aerosol reacted rapidly with water vapor in the respiratory tract to form LiOH prior to deposition. PMID- 3089862 TI - Radiopharmaceutical approved for the labeling of autologous leukocytes. PMID- 3089863 TI - [Possibility of optimizing respiratory response using biofeedback]. PMID- 3089864 TI - [6th symposium of the French Society of Enteral and Parenteral Nutrition. Toulouse, 5-6 December 1985. Abstracts]. PMID- 3089865 TI - [Malnutrition and deficiency of insulin secretion in alcoholic cirrhosis. Study by the assay of urinary C-peptide]. AB - In order to evaluate the relationship between nutritional status and insulin secretion in cirrhosis, the following parameters of caloric (tricipital skin fold, prealbumin) and proteic (arm muscle size, transferrin, 24 h-urinary creatinine excretion) nutritional status were compared in 20 alcoholic cirrhotics and 10 normal subjects. Insulin secretion was evaluated in both groups by insulin and C-peptide response to an intravenous glucose tolerance test and by 24 h urinary excretion of C-peptide. When compared to normals, cirrhotics have lower values for all nutritional status parameters and individually for at least three of those in 14 (70 p. 100) patients. In cirrhotics there is a significant decrease of the 4-min poststimulative response of insulin and C-peptide, contrasting with higher basal and late poststimulative values than in normals. This contrast could be explained by a reduced metabolic clearance rate of insulin (consistent with insulin resistance) and of C-peptide (the urinary clearance of which is 2.5 times lower in cirrhotics than in normals). The 24-h urinary excretion of C-peptide, probably weakly dependent of this reduced clearance, is 50 p. 100 lower in cirrhotics: 12.9 +/- 1.6 nM/24 h than in normals: 26.0 +/- 2.4 nM/24 h (p less than 0.001). In cirrhotics there is a significant linear correlation between 24 h urinary C-peptide excretion and all the nutritional status parameters but one (prealbumin). These results indicate that in cirrhosis: 1) urinary C-peptide excretion rate is a good index of insulin secretion; 2) urinary C-peptide indicates a marked deficit in insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089866 TI - Role of mucus in the repair of gastric epithelial damage in the rat. Inhibition of epithelial recovery by mucolytic agents. AB - A role for mucus in providing a microenvironment over sites of gastric damage, which is conducive to reepithelialization, has been proposed. We tested this hypothesis by examining the effects of disruption of such mucus on the recovery of epithelial integrity after damage induced by 50% ethanol. Exposure of an ex vivo chambered gastric mucosa to topically applied 50% ethanol resulted in copious release of mucus, cellular debris, and plasma, which formed a continuous cap over the mucosal surface. Ethanol-induced gastric damage was accompanied by extensive surface epithelial cell damage and a marked decrease in transmucosal potential difference. During the 30 min after ethanol was removed from the chamber, the epithelium became reestablished and the potential difference gradually recovered to 94% of the level before ethanol treatment. However, if the mucolytic agents N-acetylcysteine (5%) or pepsin (0.5%) were added to the bathing solutions, the "mucoid cap" disintegrated and the recovery of potential difference was significantly retarded (recovering to only 51% and 52% of levels before ethanol treatment). Histologic evaluation confirmed that mucosae treated with either agent had significantly less (p less than 0.005) intact epithelium at the end of the experiment. Removal of the mucoid cap with forceps caused a similar inhibition of the repair of the epithelium and the recovery of potential difference. Both mechanical and chemical (N-acetylcysteine) disruption of the mucoid cap resulted in a significant increase in the mucosal leakage of albumin and hemoglobin, supporting previous histologic evidence that the mucoid cap traps blood components over the damaged mucosa. These studies support the hypothesis that mucus released in response to topical application of an irritant plays an important role in the repair of epithelial damage through the process of restitution. PMID- 3089867 TI - Intestinal immunity and inflammation: recent progress. AB - The previous sections illustrate that we are still defining (a) which sets of lymphoid cells are present in the intestine and which are not, (b) which sets are peculiar to the intestine, and (c) how the sets that are there function in the intestinal microenvironment. An understanding of the latter point is going to require knowledge of how these sets communicate with and regulate one another via cell surface molecules such as MHC class I and class II molecules, and via soluble mediators or lymphokines. The recent advances in various technologies make this a particularly exciting time in this field because the tools are now available to address and answer some of these basic and important questions in mucosal immunology. At the same time these advances hold great promise for our eventual understanding of chronic inflammatory diseases of the intestine. As was mentioned at the outset, the immune system has considerable power for both protection and destruction. It remains a puzzle how this latter potential is contained and controlled in the intestine of most individuals, such that they do not have inflammatory disease even in the setting of intense stimulation by substances, such as endotoxin, that are phlogistic elsewhere in the body. An answer to the question of why everyone does not have intestinal inflammation could provide new insights into the mechanisms involved in chronic intestinal inflammatory diseases. The recent advances just detailed, as well as others sure to come, suggest that it is only a matter of time before such questions are answered. PMID- 3089868 TI - A female-specific lethal lesion in an X-linked positive regulator of the Drosophila sex determination gene, Sex-lethal. AB - Characterization of a partial-loss-of-function, female-specific lethal mutation has identified an X-linked genetic element (1-34.3; 10B4) that functions as a positive regulator of Sxl, a central gene controlling sex determination in Drosophila melanogaster. The name, sisterless-a, was chosen both to suggest functional similarities that exist between this gene and another positive regulator of Sxl, the maternally acting gene daughterless (da), and also to highlight an important difference; namely, that in contrast to da, it is the zygotic rather than maternal functioning of sis-a that is involved in its interaction with Sxl. As with da, the female-specific lethal phenotype of sis-a is suppressed both by SxlM#1, a gain-of-function mutant allele of the target gene, and, to a lesser extent, by a duplication of Sxl+. Mutations at sis-a, da and Sxl display female-specific dominant synergism, each enhancing the others' lethal effects. The allele specificity with respect to Sxl of these dominant interactions indicates that sis-a and da affect the same aspect of Sxl regulation. As with previous studies of da and Sxl, the masculinizing effects of loss of sis-a function are generally obscured by lethal effects, presumably related to upsets in dosage compensation. The masculinizing effects can be dissociated from lethal effects by analysis of triploid intersexes (XX AAA) or by analysis of diploid females who are also mutant for autosomal genes known to be required for the transcriptional hyperactivation associated with dosage compensation in males. Analysis of foreleg development shows that intersexuality generated by sis-a is of the mosaic type: At the level of individual cells, only male or female development is observed, never an intermediate sexual phenotype characteristic of true intersexes. Sexual development of diplo-X germline and somatic clones of sis-a tissue generated by mitotic recombination during larval stages is normal, as is the sexual phenotype of homozygous sis-a escapers. Considered in their totality, these results indicate that sis-a functions early in development to help establish the activity state of Sxl and thereby initiate the sexual pathway commitment, rather than functioning later in the processes by which Sxl maintains and expresses the sex determination decision. PMID- 3089869 TI - The genetics of the dorsal-Bicaudal-D region of Drosophila melanogaster. AB - The chromosomal region 36C on 2L contains two maternal-effect loci, dorsal (dl) and Bicaudal-D (Bic-D), which are involved in establishing polarity of the Drosophila embryo along the dorsal-ventral and anterior-posterior axes, respectively. To analyze the region genetically, we isolated X-ray-induced dorsal alleles, which we recognized by virtue of the haplo-insufficient temperature sensitive dorsal-dominant phenotype in progeny of single females heterozygous for a mutagenized chromosome. From the 20,000 chromosomes tested, we isolated three deficiencies, two inversions with breakpoint in dl and one apparent dl point mutant. One of the deficiencies, Df(2L)H20 (36A6,7; 36F1,2) was used to screen for EMS-induced lethal- and maternal-effect mutants mapping in the vicinity of dl and Bic-D. We isolated 44 lethal mutations defining 11 complementation groups. We also recovered as maternal-effect mutations four dl alleles, as well as six alleles of quail and one allele of kelch, two previously identified maternal effect genes. Through complementation tests with various viable mutants and deficiencies in the region, a total of 18 loci were identified in an interval of about 30 cytologically visible bands. The region was subdivided into seven subregions by deficiency breakpoints. One lethal complementation group as well as the two maternal loci, Bic-D and quail, are located in the same deficiency interval as is dl. PMID- 3089870 TI - X-linked female-sterile loci in Drosophila melanogaster. AB - We have examined the number of X-linked loci specifically required only during oogenesis. Complementation analyses among female-sterile (fs) mutations obtained in two mutagenesis screens--GANS' and MOHLER's--indicate that any fs locus represented by two or more mutant alleles in GANS' collection are usually present in MOHLER's collection. However, when a locus is represented by a single allele in one collection, it is generally not present in the other collection. We propose that this discrepancy is due to the fact that most "fs loci" represented by less than two mutant alleles are, in fact, vital (zygotic lethal) genes, and that the fs alleles are hypomorphic mutations of such genes. In support of this hypothesis we have identified lethal alleles at 12 of these "fs loci." The present analysis has possibly identified all maternal-effect lethal loci detectable by mutations on the X chromosome and has allowed us to reevaluate the number of "ovary-specific fs" loci in the Drosophila genome. Finally, germline clone analysis of a large number of fs mutations was performed in order to estimate the relative contribution of germline and somatic cell derivatives to oogenesis and to embryonic development. All the maternal-effect lethal loci tested are germline-dependent. PMID- 3089871 TI - [Construction of the hybrid crp-lac operon and study of the role of CRP-cAMP complex in its regulation in Escherichia coli]. AB - Phage Mu d1(Ap,lac) was used to construct the hybrid crp-lac operon in Escherichia coli cells possessing crps mutation which increases sensitivity of bacterial growth to exogenous cAMP. Transcription of the structural lac genes in this hybrid operon was initiated from the promoter region of the crp gene. By measuring levels of beta-galactosidase enzyme, the maximal transcription of the crp gene was obtained in strains with cya or crp mutations causing inactivation of the CRP - cAMP complex. Restoration of cya+crp+ genotype resulted in 5 to 7 times decrease of the lacZ gene activity. At the concentration of exogenous cAMP which induces catabolic derepression in the wild-type strain, the expression of crp-lac operon increased 2-3 times. Using F'ts114lac-mediated chromosome mobilization, the direction of transcription of the crp gene was found to be counterclockwise, relative to the E. coli genetic map. PMID- 3089872 TI - [Organization and gene expression of plasmid ColD-CA23 connected with colicin biosynthesis]. AB - Organization of genes for colicin, immunity and lysis and regulation of their expression in colicinogenic plasmid ColD-CA23 were studied. The polypeptides synthesised in minicells carrying the ColD plasmid, its Tn5 mutants and the recombinant plasmids constructed by cloning the ColD EcoRV fragments on pBR325 were analysed. The position of the colicin gene promotor is established and direction of the gene transcription determined. The immunity gene was shown to be expressed independently of the gene coding for colicin and believed to have its own SOS-independent promotor. Treatment with mitomycin C of the ColD-carrying cells leads to induction of the synthesis both of colicin and of a 10 KD protein responsible for cell killing and lysis. This protein can be detected in a cultural medium under lysis. Plasmid mutations abolishing synthesis of the lysis protein prevent release of colicin. The colicin and lysis genes are arranged in an operon, the lysis gene being situated next to that of colicin. The ColD genetic map is suggested. PMID- 3089873 TI - [Operon of riboflavin biosynthesis in Bacillus subtilis. XVII. A study of the regulatory functions of the intermediate products and their derivatives]. AB - Repression of synthesis of GTP-cyclohydrolase and riboflavinsynthetase was studied in different regulatory mutants of Bacillus subtilis. The results of experiments with some riboflavin precursors and their derivatives revealed that 5 amino-2,6-dioxo-4-ribitylaminopyrimidine and 6-methyl-7-(1',2'-dioxyethyl)-8 ribityllumazine can serve as effectors in riboflavin biosynthesis. PMID- 3089874 TI - Isolation of a cDNA clone for chick intestinal apolipoprotein AI (Apo-AI) and its use for detecting apo-AI mRNA expression in several chick tissues. AB - Three cDNA clones for chick apolipoprotein AI (Apo-AI), the major protein component of plasma high-density lipoproteins, have been isolated. The identity of the clones has been established first by screening a cDNA library in the pEX1 expression vector with anti-Apo-AI antibodies, second by Western blot analysis of the proteins expressed by positive clones. The use of the clone containing the largest, presumably full-size, cDNA insert (apo5C12) in molecular hybridization experiments confirms that apo-AI mRNA is expressed mainly in chick small intestine and liver. Furthermore, we provide evidence that brain, heart and skeletal muscle also synthesize significant amounts of apo-AI mRNA. The Southern blot hybridization pattern of the restriction-enzyme-digested chick DNA with the apo5C12 DNA is consistent with there being a single copy of the apo-AI gene. PMID- 3089876 TI - Nucleotide sequence analysis of the phosphomannose isomerase gene (pmi) of Pseudomonas aeruginosa and comparison with the corresponding Escherichia coli gene manA. AB - Phosphomannose isomerase (PMI) has been proposed to catalyze the first step of the alginic acid biosynthetic pathway in Pseudomonas aeruginosa. The nucleotide sequence of the P. aeruginosa pmi gene contained on a 2.0-kb BamHI-SstI DNA fragment has been determined. The gene was defined by the start and stop codons and by in vitro disruption of an open reading frame of 1440 bp corresponding to a polypeptide product with a predicted Mr of 52 860. This polypeptide displayed an apparent Mr of approx. 56 000 upon electrophoresis of a maxicell extract on sodium dodecyl sulfate-polyacrylamide gels. The codon utilization of the pmi gene was distinct in the wobble base preference and influenced by the high G + C content (66 mol%) of the P. aeruginosa DNA. Computer assisted matching analysis failed to demonstrate any significant homology at the nucleotide level between the P. aeruginosa pmi and Escherichia coli manA (pmi) genes. However, sequences homologous to the P. aeruginosa pmi gene were found in other Pseudomonas species, such as P. putida and P. mendocina, and in Azotobacter vinelandii, all capable of producing alginic acid. PMID- 3089877 TI - Community-based long-term care models, target groups, and impacts on service use. PMID- 3089875 TI - Molecular cloning of human C1 inhibitor: sequence homologies with alpha 1 antitrypsin and other members of the serpins superfamily. AB - Genetic and acquired diseases in man show that the proteolytic activity of the complement component C1 is crucially regulated by C1 inhibitor (C1-INH), a plasma protein whose suspected relatedness to other serine proteinase inhibitors (serpins) contrasts with its atypically large size and high degree of glycosylation. Indeed we have found that the C1-INH polypeptide precursor synthesized in a cell-free system is a 64-kDa protein, hence it exceeds the length of the precursor forms of typical serpins. Seeking more conclusive sequence information and a probe for the structural locus, we isolated C1-INH cDNA clones from a library representing size-enriched human liver mRNA. Nucleotide sequence analysis of a clone covering the carboxyterminal half of C1 INH conclusively documents the relatedness of this protein with the serpins, and reveals 27% amino acid identity with alpha 1-antitrypsin. PMID- 3089879 TI - Effects of state Medicaid policies on the aged. PMID- 3089878 TI - Case management approaches in coordinated community-oriented long-term care demonstrations. PMID- 3089881 TI - PCB intake and the growth of waterfowl: multivariate analyses based on a reparameterized Richards sigmoid model. AB - Multivariate analyses of the parameters of a modified Richards growth model were used to determine the effects of sex and varying levels of dietary intake of PCB's (0-50 ppm), on the asymptotic size (W infinity), total growing time (T) and shape (m) of the growth curves of game farm mallards (Anas platyrhynchos) and wild wood ducks (Aix sponsa) raised under laboratory conditions. Level of PCB intake did not affect any of the growth parameters of the wood ducks, while sex affected both m and W infinity, with males of this species growing to greater body weights and showing slightly lower shape parameters than females. Growth characteristics of the mallards on the other hand, did not differ between the sexes. PCB intake however, had a significant effect on the shape of the mallard growth curve, but did not affect either W infinity or T. All interactions between sex and PCB treatment level were non-significant in both species. The growth responses of game-farm mallards to PCB intake cannot be assumed to typify that of other wild waterfowl species without additional evidence from comparative studies. PMID- 3089880 TI - [Inhibitor of the coagulating fraction of factor VIII in the puerperium]. PMID- 3089882 TI - Episodic patterns of growth hormone secretion and growth hormone status of normal and tibial dyschondroplastic chickens. AB - Growth hormone status of normal and tibial dyschondroplastic (TD) birds was determined in 25 d old male chicks genetically selected for high and low incidence of TD. Birds were surgically prepared with indwelling venous catheters and blood samples remotely removed at 20 min intervals for 6 h to establish secretory patterns. Birds were maintained under a 16L:8D cycle, with free access to feed and water at all times. In a second experiment, secretory capacity was evaluated by administering a 10 micrograms/kg body weight dose of thyrotrophin releasing hormone (TRH). Blood samples were removed at 0, 5, 10, 20, 30, 60 and 120 min post-infusion of either TRH or saline (control). All birds displayed pulsatile patterns of GH secretion, with an average peak duration of 60 min and a 90 min inter-peak interval. Dyschondroplastic birds exhibited 50% higher mean peak amplitudes than normal birds (P less than .06), however, this difference was not translated into overall mean or total (curve area) differences. The magnitude of response to a TRH challenge was greater (P less than .10) for TD than for normal birds. In view of the relationships observed in other species between secretory pattern characteristics such as peak amplitude, and growth characteristics, it is suggested that differences in GH status of dyschondroplastic relative to normal birds may be related to initiation of the TD lesion. PMID- 3089883 TI - Partial gastric diverticula: radiological and endoscopic features in six patients. AB - Partial gastric diverticula are rare and clinically insignificant, but because experience is limited, they are liable to cause diagnostic confusion. This report describes the radiological and endoscopic appearances of partial gastric diverticula. PMID- 3089884 TI - [Percutaneous endoscopic gastrostomy]. PMID- 3089885 TI - [Active pulmonary tuberculosis in lung cancer]. PMID- 3089886 TI - [Periarticular new bone formation associated with head injuries]. PMID- 3089887 TI - [Intestinal pseudo-obstruction in an infant]. PMID- 3089888 TI - [Ventilatory control and breathing pattern in chronic obstructive pulmonary disease]. PMID- 3089889 TI - [Post-traumatic epilepsy]. PMID- 3089890 TI - [Transdermal therapeutics]. PMID- 3089891 TI - The influence of continuous intrauterine infusion of enzyme-inhibitors of the arachidonic acid cascade on ovulation and tubal ovum transport in the hyperstimulated rabbit. AB - Cyclo-oxygenase and prostaglandin-15-hydroxydehydrogenase are rate-limiting steps in the arachidonic acid cascade. These enzymes were affected by indomethacin and lonazolac treatment in hyperstimulated rabbits through continuous intrauterine or single vaginal applications in three different experiments. In terms of the ovulation-index, there was no difference between animals treated via the intrauterine or the vaginal routes. Compared with controls (83 to 89%), there was a significant reduction in the ovulation index to 32% with indomethacin and to 51 or 55% with lonazolac, 28 h after induction of ovulation (experiment 1). The values turned almost back to normal 52 h after induction of ovulation 72% (experiment 3). The treatment with lonazolac resulted in a higher sum of corpora lutea and unruptured follicles (experiment 1: control-group = 90.9 vs lonazolac group = 110.5). The recovered ova showed a shift from the 4 and 8 cell stages to the 16 or more cell stages under lonazolac treatment when compared with controls (experiment 3). The histologic examinations showed advanced luteinization of unruptured follicles in the indomethacin-treated groups. Hyperplasia of the theca interna was also noted. Our data indicate that indomethacin was capable of inducing premature luteinization resulting in arrested or delayed ovulation. Lonazolac, in contrast, did not impair ovulation. Moreover, it induced the growth of more follicles, probably through a second wave at the time of ovulation initiated by hCG. For the clinical practice these experiments point towards the possibility of the treatment of the luteinized unruptured follicle syndrome and towards the application of lonazolac for ovarian stimulation. PMID- 3089892 TI - Impaired glucose tolerance coincides with abnormal release of growth hormone following a glucose load as well as in response to TRH in acromegaly. AB - It is known that some acromegalic patients exhibited a paradoxical release of growth hormone (GH) after glucose administration. We have attempted to investigate a relationship between the paradoxical GH secretion with the abnormal glucose tolerance test present in some cases of acromegaly. We also studied the inappropriate increase in GH levels following thyrotropin releasing hormone (TRH) injection which is present in some acromegalics. We found that only those patients who had an abnormal glucose tolerance test exhibited simultaneously, the paradoxical release of GH, moreover, the same patients showed GH release following TRH administration. This observation suggests that some acromegalics have an abnormality in their hypothalamic glucose receptor and such abnormality is associated with abnormal GH secretion when TRH is administered. On basis of these findings it is suggested that the hypothalamus may play an important role in the pathogenesis of acromegaly in these cases. PMID- 3089893 TI - Influence of central dopaminergic activity on thyrotropin responsiveness to thyrotropin-releasing hormone in normal and thyrotoxic subjects. AB - To study whether central dopaminergic activity influences TSH responsiveness to TRH in normal individuals and in patients with hyperthyroidism, three experiments (A, B and C) were carried out in 8 normal subjects, and two experiments (A and B) in 8 patients with untreated thyrotoxicosis. In experiment A oral placebo (PBO) preceded iv administration of 200 micrograms TRH by 90 min. In experiment B dopamine receptor blockade with 15 mg oral metoclopramide (MET) was given 90 min before iv administration of 200 micrograms TRH. In experiment C two oral doses (each dose 2.5 mg) of bromocriptine (BCT), known for dopamine agonistic properties, were given 9 and 1 hour before ingestion of 15 mg MET which, in turn, preceded iv injection of 200 micrograms TRH by 90 min. In the healthy subjects experiment A revealed a TSH responsiveness, as reflected by the TSH incremental area, which was 430 +/- 74. The corresponding TSH responsiveness was significantly larger in experiment B (661 +/- 138; P less than 0.02). In experiment C the TSH incremental area (332 +/- 102) did not differ significantly from the one obtained in experiment A. The thyrotrophs responded quite different to TRH in the group of thyrotoxic patients, where the TSH incremental area was zero regardless of whether PBO or MET were given as oral pretreatments. These results imply that central dopaminergic activity inhibits the pituitary thyrotrophs and modulates the TSH response to TRH in healthy subjects, but does not contribute significantly to the blocked TSH responsiveness in patients with untreated hyperthyroidism. PMID- 3089894 TI - Characterization and clinical relevance of a new complement-fixing antibody--anti M8--in patients with primary biliary cirrhosis. AB - A new complement-fixing antimitochondrial antibody--anti-M8--was detected in patients with primary biliary cirrhosis. Anti-M8 was only found in association with anti-M2, however, not all anti-M2 positive patients had anti-M8. Thus, among 66 anti-M2 positive patients, 29 were also positive for anti-M8, whereas sera from patients who had the complement-fixing anti-M2 and anti-M4 antibodies in parallel always strongly reacted with the M8 antigen. This group was previously described as mixed form. The M8 antigen was isolated either from human liver mitochondria or pig kidney microsomes and could be clearly distinguished from the M4 antigen. In contrast to M4, M8 was trypsin sensitive and banded at sucrose densities from 1.16 to 1.24, while M4 was found at densities from 1.08 to 1.14. Like M4, the M8 antigen also co-purified with outer mitochondrial membranes. Fifty-three patients with primary biliary cirrhosis have been followed over a period of up to 16 years and were classified according to their complement-fixing antimitochondrial antibody profile. At the time of the first diagnosis, 95% of 31 patients being anti-M2 positive, but anti-M8 negative (antimitochondrial antibody Profile I) were in Stage I or II. In contrast, only 61% of 13 patients being anti M2 and anti-M8 positive (antimitochondrial antibody Profile II) and 44% of 9 patients with anti-M2, anti-M8 and anti-M4 in parallel (antimitochondrial antibody Profile III) belonged to Stage I or II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089895 TI - The calcium ionophore A23187 stimulates glycoprotein secretion by the guinea pig gallbladder. AB - The purpose of this study was to examine the role of calcium ions in gallbladder glycoprotein secretion in cultured guinea pig gallbladder explants. The calcium ionophore A23187 showed a threshold of 2 micrograms per ml medium for stimulation of secretion of [3H]glucosamine-labeled glycoproteins over a 30 min incubation period. The ionophore at 3 and 5 micrograms per ml medium resulted in a 3- to 4 fold increase in secretion of [3H]glucosamine-labeled glycoproteins. Ionophore induced stimulation of glycoprotein secretion was abolished by the addition of 0.01 mM verapamil to the medium. To study the effect of changes in extracellular calcium on basal glycoprotein secretion, explants were cultured for 24 hr in media with 0.007, 0.5 or 2.0 mM calcium; no differences in basal glycoprotein secretion were observed. When cultured in medium with 1.0 mM EGTA, basal secretion decreased significantly vs. controls in 0.007 mM total calcium medium. Total [3H]glucosamine incorporation by explants in medium with EGTA was unaltered, however, suggesting that the low level of calcium in the medium was selectively impairing the secretory process. These findings indicate that calcium ions are important in the regulation of gallbladder glycoprotein secretion. PMID- 3089896 TI - Leucine metabolism in stable cirrhosis. AB - Alterations in protein and amino acid metabolism have been postulated to explain the frequent observations of muscle wasting and decreased plasma branched-chain amino acid concentrations in cirrhosis. In order to investigate the changes in protein metabolism, we have measured the rates of leucine turnover and oxidation in six stable, biopsy-proven cirrhotics and six age and sex-matched healthy control subjects after an overnight fast, using [1-13C]leucine tracer. Following a primed constant-rate infusion of [1-13C]leucine, the 13C enrichments of plasma leucine and expired CO2 were used to estimate leucine turnover and oxidation, respectively. Fat-free body mass was estimated from the measurements of total body water as quantified by H2[18O] tracer dilution. The rates of CO2 production and oxygen consumption were measured hourly during the study period, using open circuit respiratory calorimetry. Urinary urea, ammonia and total nitrogen excretion rates were quantified from timed urine samples. Even though the plasma leucine levels were lower in cirrhotics as compared with controls (100.5 +/- 17.1 vs. 138.3 +/- 20.4 mumoles per liter, mean +/- S.D., p less than 0.001), the rates of leucine turnover were not significantly different in the two groups (89.4 +/- 19.0 vs. 87.8 +/- 19.0 mumoles per kg X hr). In contrast, the rates of leucine oxidation were significantly reduced in cirrhosis (8.1 +/- 2.5 vs. 12.7 +/- 3.1 mumoles per kg X hr, p less than 0.01). When all subjects were considered, the leucine oxidation rate was correlated with plasma leucine concentration (r = 0.62, p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089897 TI - Drug targeting to the liver with lactosylated albumins: does the glycoprotein target the drug or is the drug targeting the glycoprotein? AB - The isolated perfused rat liver preparation was employed to study hepatic disposition of the model drug-carrier conjugate fluorescein-lactosylated albumin (F-LnHSA) with special reference to the influence of the organic anion fluorescein on liver cell specificity of the endocytosed neoglycoprotein. Hepatic clearance of fluoresceinated neoglycoproteins was significantly faster than clearance of radioiodinated neoglycoproteins. Perfusate clearance of F-L7HSA and F-L25HSA could not completely be inhibited by a dose of 10 mg asialoorosomucoid that saturates the hepatocyte receptor-mediated endocytic process. From these data, we inferred an additional hepatic uptake mechanism, competing with the Ashwell-receptor-mediated internalization of galactose-terminated glycoproteins. Clearance experiments with fluoresceinated 125I-human serum albumin in the presence of the polyanionic probe dextran sulfate revealed a nearly complete (approximately 90%) inhibition of hepatic uptake, while also a pronounced effect was obtained with colloidal carbon. These data point to nonparenchymal cell uptake of fluoresceinated protein via interaction with scavenger receptors. In wash-out studies, it was shown that about 25% of ligand sequestrated by sinusoidal liver cells escaped degradation and recycled to the perfusion medium. Our results show that care should be taken in the use of neoglycoproteins as drug carriers to hepatocytes, since a load of only 2 to 3 moles fluorescein per mole neoglycoprotein considerably affects intrahepatic distribution. The relative contribution of nonparenchymal cell uptake by coupling of acidic drugs to the neoglycoproteins is very probably inversely related to the number of exposing galactose groups per molecule neoglycoprotein. This phenomenon of "inversed targeting" could therapeutically both be useful or detrimental, dependent on the spectrum of cell types that should be reached by the drug. PMID- 3089899 TI - Effects of proprietary management in general hospital psychiatric units. AB - The rapid increase in the number of proprietary psychiatric hospitals during the last 15 years has drawn criticism from those concerned about the impact of the profit motive on the quality of patient care. This study assessed changes in the structure and quality of care on 13 acute care psychiatric units before and after a single outside proprietary firm was hired to manage the units. The study found significant improvements in many areas after the change; they included higher occupancy rates, higher staffing levels, more hours of staff inservice training, higher collections-to-billings ratios, and improved program structure and process as measured by Joint Commission on Accreditation of Hospitals criteria. No changes were found in the length of stay or diagnostic mix of patients. The findings indicate that program quality and profit are not necessarily incompatible, but the author cautions against making generalizations to other situations based on the small study sample. PMID- 3089898 TI - Multilobated B-cell lymphoma, a variant of centroblastic lymphoma. Report of four cases. AB - Four cases of multilobated B-cell lymphoma, one follicular and three diffuse, are described. Many of the lymphoma cells show marked lobulation of the nuclei, and possess multiple prominent nucleoli. There are admixed classical centrocytes, classical centroblasts, and cells with morphology intermediate between classical centroblasts and multilobated cells. Multilobated cells are also observed in small numbers in germinal centres of lymph nodes showing reactive follicular hyperplasia. We believe that the multilobated B-cell may represent one form of centroblast during transition between the centroblastic and centrocytic stages. Multilobated B-cell lymphoma may be its neoplastic counterpart in which the nuclear lobulation is further exaggerated. PMID- 3089900 TI - DRGs fail to spur cost containment in NJ hospitals. PMID- 3089901 TI - Abnormal patterns of colorectal mucin secretion after urinary diversion of different types: histochemical and lectin binding studies. AB - Clinical and experimental evidence indicates that ureterosigmoidostomy is associated with a high risk for the development of colonic cancer, while there is no reported evidence of increased risk in patients who undergo urinary diversion of other types. In the present study the histochemical and lectin binding characteristics of goblet cell mucin were investigated in biopsy specimens from patients who had undergone ureterosigmoidostomy and from patients who had undergone rectal bladder surgery. Specimens from transitional mucosa surrounding colonic cancers and from normal rectal mucosa were also studied. For histochemical studies the high iron diamine-Alcian blue method was used. FITC conjugated Dolichus biflorus agglutinin (FITC-DBA) and Arachis hypogaea agglutinin (FITC-PNA) were used for the study of lectin binding characteristics. In contrast to the striking increase in numbers of sialomucin-containing goblet cells found in the patients who had undergone ureterosigmoidostomy, the mucin proved to be histochemically normal in the rectal bladder surgery group. Abnormal lectin binding patterns were observed in colorectal mucosa after urinary diversion of both types, with the abnormalities consisting of dramatic decreases in FITC-DBA labeling (compared with controls) and the appearance of substantial numbers of FITC-PNA-labeled goblet cells. These findings indicate that the pattern of mucin secretion is definitely abnormal in patients who have undergone urinary diversion. Whether this abnormality is an indicator of premalignant changes remains to be established. These data, however, confirm that endoscopic and histologic follow-up studies may be of value in assessing the risk for the development of cancer in these patients. PMID- 3089902 TI - Altered cellular response to UV irradiation in a patient affected by premature ageing. AB - An abnormal response to UV-irradiation was found in a patient affected by precocious senescence. A decreased level of unscheduled DNA synthesis (UDS) was present in 60% of Go lymphocytes and in fibroblasts after the fifth culture passage. Hypersensitivity of lymphocytes to UV-light was indicated also by a decreased rate of DNA synthesis after mitogen stimulation. The results of this study indicate that the defect which determines the premature ageing influences the capacity to repair UV-induced DNA damage. PMID- 3089904 TI - Molecular and epidemiological analysis of penicillinase producing strains of Neisseria gonorrhoeae isolated in Canada 1976-84: evolution of new auxotypes and beta lactamase encoding plasmids. AB - Though the number of penicillinase producing Neisseria gonorrhoeae (PPNG) strains isolated in Canada comprises under 1% of all gonococcal isolates, it continues to increase appreciably each year. Most strains are imported from areas of endemic infection with PPNG strains. Two local outbreaks in 1984, however, were notable for the number of patients infected and for the distinctive phenotypes of the strains. One outbreak was caused by a wild type strain, of serovar BACJK with a new 3.05 megadalton penicillinase encoding plasmid, whereas the other was caused by strains with the Asia+ plasmid type, serovar AE and with a proline and ornithine requiring auxotype. Five plasmid patterns (Africa+, Africa-, Asia+, Asia-, and Toronto+) were observed among the PPNG strains. The association between plasmid content and specific auxotype (such as Asia plasmid with proline requiring auxotype or Africa plasmid with wild type auxotype) and inhibition by phenylalanine continues to be unexplained. PMID- 3089903 TI - Epidemiological analysis of Neisseria gonorrhoeae in the Federal Republic of Germany by auxotyping and serological classification using monoclonal antibodies. AB - We evaluated a new serological classification system for Neisseria gonorrhoeae based on monoclonal antibodies directed against epitopes on the outer membrane protein I, in conjunction with auxotyping, to analyse gonococci from two cities in the Federal Republic of Germany. Isolates of N gonorrhoeae were collected during 1976-8 and 1980-2 in Lubeck, and during 1980-2 in Heidelberg. Between the two study periods in Lubeck, we observed an appreciable decrease in strains of the auxotype that requires arginine, hypoxanthine, and uracil (AHU-) and with serovar class PrIA-1 and the emergence of strains with the proline requiring auxotype and PrIB-1 serovar class. Serovar PrIA-1 accounted for 89 (97%) of 92 strains with the AHU- auxotype as opposed to 12 (4%) of 297 strains with other auxotypes (p less than 0.0001). Disseminated gonococcal infection was associated with AHU-/PrIA-1 strains. Penicillinase producing N gonorrhoeae (PPNG) strains belonged to eight different auxotype and serovar classes, which indicated that different strains had been imported. Classification of strains of N gonorrhoeae by auxotype and serovar class permits analysis of temporal changes in gonococcal populations, and of migrations of gonococci between different geographical areas. Typing N gonorrhoeae, together with assessing antibiotic susceptibilities, may prove useful for further studies of the epidemiology and control of gonorrhoea. PMID- 3089905 TI - Incidence of gonorrhoea due to penicillinase producing Neisseria gonorrhoeae in Japan 1981-3 and treatment using a new antibiotic combination, BRL25000 (amoxycillin and clavulanic acid). AB - During the three years 1981-3, 134 (9.1%) of 1473 patients presenting at our clinics were found to be infected with penicillinase producing strains of Neisseria gonorrhoeae (PPNG). Minimum inhibitory concentrations (MICs) of benzylpenicillin and ampicillin against these PPNG strains were 8 mg/l or more, whereas against non-PPNG strains they were consistently 4 mg/l or less. In contrast, the MIC of BRL25000 (two parts amoxycillin and one part clavulanic acid, the beta lactamase inhibitor) was 4 mg/l or less even against PPNG strains. MICs of a number of other drugs commonly used to treat gonorrhoea, such as cephaloridine, cefoxitin, tetracycline, doxycycline, minocycline, kanamycin, and spectinomycin, showed no appreciable differences between non-PPNG and PPNG strains and the MIC of cephaloridine in particular was relatively high. BRL25000 proved to be very effective in the treatment of PPNG infection and cured all of 121 patients treated. A daily dose of 2.25g, cured 105 patients in two days, 11 patients in three days, four patients in four days, and one patient in five days. A new rapid diagnostic method for detecting PPNG strains, capable of application at an outpatient clinic and providing a result on the following day, is described. PMID- 3089906 TI - Antimicrobial activity of seven metallic compounds against penicillinase producing and non-penicillinase producing strains of Neisseria gonorrhoeae. AB - The in vitro activity of seven metallic compounds was tested against penicillinase (beta lactamase) producing strains of Neisseria gonorrhoeae (PPNG) and non-PPNG strains. On a weight basis, the mercurials showed the greatest in vitro activity. Phenylmercuric borate, thiomersal, and mercuric chloride inhibited 90% of all strains at concentrations of 5 mg/l, 5 mg/l, and 20 mg/l respectively. Silver nitrate inhibited 90% of the strains at 80 mg/l and the MIC90 for mild silver protein was 200 mg/l. Copper and selenium salts had lower in vitro activities, inhibiting 90% of all the strains at 320 mg/l and 640 mg/l respectively. Silver nitrate and the six other compounds tested showed equal activities against PPNG and non-PPNG strains. This finding supports the recommendation for prophylaxis of gonococcal conjunctivitis of the newborn with 1% silver nitrate eye drops. PMID- 3089908 TI - Comparison of clinical and epidemiological characteristics of pelvic inflammatory disease classified by endocervical cultures of Neisseria gonorrhoeae and Chlamydia trachomatis. AB - We compared the clinical and epidemiological characteristics of 89 women with pelvic inflammatory disease (PID) seen at a clinic for sexually transmitted diseases during 1982 and 1983. Patients were classified into four groups by having endocervical cultures positive for Neisseria gonorrhoeae only (24), Chlamydia trachomatis only (16), both organisms (14), or neither organism (35). More women with cultures positive for N gonorrhoeae were black (p less than 0.005), had a sexual partner with gonorrhoea (p less than 0.005), and had a purulent vaginal discharge (p less than 0.05). No other significant differences were found between groups regarding age, exposure to a sexual partner with non gonococcal urethritis, history of trichomoniasis, parity, use of antibiotics, contraceptive history, duration of abdominal pain, relation of pain to the phase of the menstrual cycle, abdominal rebound tenderness, reproductive tract signs, or febrility. In women presenting to outpatient clinics, PID tends to be mild and the diagnosis unreliable. Though C trachomatis is emerging as an important aetiological agent, we found no clinical indicators that could distinguish chlamydial from gonococcal PID. PMID- 3089907 TI - Single dose cefoxitin in treating uncomplicated gonorrhoea caused by penicillinase producing Neisseria gonorrhoeae (PPNG) and non-PPNG strains. AB - A total of 136 patients with uncomplicated gonorrhoea were treated with intramuscular cefoxitin 2 g (25 patients) or 1 g (111 patients) and oral probenecid 1 g. Cefoxitin 1 g cured 95% (42 out of 45 men and all of 14 women) with infections caused by penicillinase producing Neisseria gonorrhoeae (PPNG) strains and 98% (all of 38 men and 13 out of 14 women) with non-PPNG infections, giving an overall cure rate of 96%. The rate of postgonococcal urethritis (PGU) in men treated with 1 g cefoxitin was 28%. No serious side effects of treatment were observed in patients treated with either dose. The failure rate of 7% in men infected with PPNG strains who were treated with the 1 g dose is, however, disturbing. We therefore recommend that intramuscular cefoxitin 2 g and oral probenecid 1 g may be used to treat uncomplicated gonorrhoea, especially in areas where PPNG strains are common. PMID- 3089910 TI - Antimicrobial substances in urine of patients attending department of genitourinary medicine. AB - The prevalence of antimicrobial substances in the urine of new patients attending a genitourinary department and patients reattending with a new condition (rebook patients) was 4.1% (33 of 812 patients). Only 17 of 33 patients (52%) found to have an antimicrobial in the urine declared their antimicrobial intake at their initial physician interview and examination. The presence of antimicrobial substances had little influence on the diagnosis or management of patients. PMID- 3089909 TI - Treating pelvic inflammatory disease with doxycycline and metronidazole or penicillin and metronidazole. AB - The best way of treating pelvic inflammatory disease (PID) is not known. The clinical response to two treatment regimens (penicillin plus metronidazole v doxycycline plus metronidazole) was studied in 33 patients with PID confirmed by laparoscopy and endometrial biopsy. The overall failure rate, according to the criteria used in this study was five of 11 (45%) women with chlamydial PID, none of six women with gonococcal PID, all of four women with chlamydial gonococcal PID, and three (25%) of 12 women with non-chlamydial non-gonococcal PID. The failure rate with penicillin plus metronidazole treatment was unacceptably high (53%), and significantly higher than that with doxycycline plus metronidazole (19%) (p = 0.038). In most cases the microbiological and histopathological evaluations identified a probable explanation for the poor response to the treatment regimen used. PMID- 3089912 TI - Massive glibenclamide overdose without hypoglycaemia in a man with diabetes after partial pancreatectomy. AB - A 49-year-old man with non-insulin-dependent diabetes mellitus (NIDDM) from alcoholic pancreatitis took 100 mg of glibenclamide without symptoms of hypoglycaemia even when glibenclamide concentrations were high (191 micrograms/l). There was no increase in serum C-peptide concentration. The observed half-life of glibenclamide was 6 h. It is concluded that high doses of glibenclamide will not provoke pancreatic insulin secretion in NIDDM caused by pancreatic destruction, there was no evidence for an acute extra-pancreatic effect of glibenclamide and the elimination of glibenclamide may be slower than supposed previously. PMID- 3089911 TI - Influence of dosing interval and in-patient versus out-patient status on incidence of side-effects of niridazole. AB - The side-effects of niridazole used for urinary schistosomiasis were studied prospectively over a 3-month period in male patients receiving the standard dose of 25 mg day-1 kg-1 for 7 days. Side-effects were detected in 80% of in-patients but only in 33% of out-patients. The range of side-effects was greater in in patients taking their daily doses in two portions than in those taking theirs in three. Cure rates and degree of schistosoma egg suppression were significantly lower in out-patients suggesting that compliance with treatment was poorer. PMID- 3089913 TI - Optimal respiratory controller structures. PMID- 3089914 TI - Antigen-driven selection of virgin and memory B cells. AB - This review has summarized the evidence indicating that far more B cells are produced in adult bone marrow than are required to maintain B cell numbers in the periphery. It is shown that most if not all these newly-formed B cells have the potential to become mature peripheral B cells. However, to do this they need to receive an appropriate signal in secondary lymphoid organs. Cells failing to receive such a signal die after a brief period. Two separate situations have been identified which result in recruitment of newly-formed virgin B cells into the peripheral B-cell pool: Following activation by antigen. When the peripheral B cell pool has been depleted. It is proposed that the first of these signals requires T help and is initiated by antigen presented on interdigitating cells in extrafollicular areas of secondary lymphoid organs. This process seems to be confined to periods immediately following administration of antigen and does not continue in established immune responses to thymus-dependent antigens. It seems probable that continued B cell activation, occurring during long term antibody responses, takes place in the follicles of secondary lymphoid organs and is driven by antigen presented on follicular dendritic cells. Indirect evidence is cited which suggests that somatic mutation in rearranged immunoglobulin V-region genes occurs mainly following B-cell activation in follicles and not during primary B lymphopoiesis. It is suggested that this may involve a hypermutation process which is switched on in activated B cells in germinal centers. Evidence is presented suggesting that plasma cells generated from B cells activated early in immune responses have an average life-span of less than 3 d. However, plasma cells generated in established responses appear to have an average life-span in excess of 20 d. Later sections in the review consider how B-cell recruitment in thymus-independent antibody responses differs markedly from recruitment during thymus-dependent responses. The possible role of splenic marginal zone B cells in some thymus-independent antibody responses is discussed and the evidence indicating that SIgM + ve, IgD-ve marginal zone B cells develop as a distinct population from recirculating SIgM + ve, IgD + ve B cells is summarized. PMID- 3089915 TI - Characterization with monoclonal antibodies of human lymphocytes active in natural killing and antibody-dependent cell-mediated cytotoxicity of dengue virus infected cells. AB - Non-immune human peripheral blood lymphocytes (PBL) lyse dengue virus-infected cells to a greater degree than uninfected cells. In the present study, the PBL active in lysing dengue virus-infected Raji cells are characterized using monoclonal antibodies and are compared to lymphocytes that lyse K562 cells. Leu11+ cells lyse dengue virus-infected cells and K562 cells. Leu11- cells lyse dengue virus-infected cells, but not K562 cells. In the Leu11+ fraction, Leu11+ Leu7- cells are more active than Leu11+ Leu7+ cells in lysing dengue virus infected cells. T3+ cells also lyse dengue virus-infected cells, but they do not lyse K562 cells. T3- cells lyse both target cells. These results, along with the observation that Leu11+ cells and T3+ cells are different subsets of PBL, indicate that the PBL that are active in lysing dengue virus-infected cells are heterogeneous and are contained in Leu11+ and T3+ subsets. Leu11+ cells are more active than T3+ cells. Leu11+ cells are active in lysing dengue virus-infected cells by antibody-dependent cell-mediated cytotoxicity, whereas T3+ cells are not active. PMID- 3089916 TI - Analysis of synthetic sites of fourth and fifth components of serum complement system in allogeneic bone marrow chimaeras. AB - Synthetic tissue sites for the fourth and fifth components of complement (C4 and C5) have been investigated using allogeneic bone marrow chimaeras in mice. One group of chimaeric mice was prepared by transplanting bone marrow cells from C5 sufficient donor mice into irradiated C5-deficient recipients or vice versa, and another group was prepared by transplanting marrow cells from mice that produce high levels of C4 into irradiated recipients that are characterized by having low levels of C4 or vice versa. In such chimaeras, lymphoid cells and serum immunoglobulin allotypes were shown to be exclusively of donor origin. However, haemolytic activities of sera from the chimaeras were consistently identical with those of normal mice of the recipient strain. Similar results were obtained when the complement component levels of the sera were evaluated by double diffusion assays. C4 or C5 antigens were detected in sera of the chimaeras only when recipients were strains that are characterized by having high C4 level or were C5 sufficient mice, respectively. These findings indicate that circulating C4 or C5 complement components present in the blood are not synthesized primarily by cells that are descendants of bone marrow cells in these chimaeric mice. PMID- 3089917 TI - C3 activation by a new factor B-dependent enzyme detected in culture supernatant from guinea-pig peritoneal macrophages. AB - Culture supernatants (c.s.) collected from thioglycollate-elicited macrophages were concentrated and incubated with purified C3. In this reaction mixture loss of haemolytic C3 according to classical enzyme kinetics was observed. As revealed by SDS-PAGE, c.s.-catalysed fragmentation of the C3 alpha-chain occurred. The cleavage products were identified by size and function as C3a and C3b. The apparent molecular weight of this C3-activating enzyme in c.s. was approximately 220,000 according to ultracentrifugation studies. This large enzyme showed the following characteristics: it had no activity against C5; it was inhibited by EDTA; Mg2+ was required for its optimal function; its half-life at 37 degrees was approximately 35 min; it was completely inhibited by anti-B IgG. Thus, we were able to detect a C3-activating enzyme in c.s. containing B but differing otherwise from a preformed C3 convertase of the alternative pathway. The exact component composition of this new enzyme is under further investigation. PMID- 3089918 TI - Polyclonal antibody formation of human lymphocytes to bacterial components. AB - The capacity of various bacterial components to induce antibody formation in human lymphocyte cultures was studied in the present investigation. Antibody levels were determined by an enzyme-linked immunosorbent assay (ELISA). Lipopolysaccharide (LPS), bacterial cell walls (CW, isolated from Bacillus subtilis and Staphylococcus aureus Wood 46) and peptidoglycans (PG) appeared to stimulate IgM, IgG and IgA secretion, whereas lysozyme-solubilized PG and teichoic acids (TA) were ineffective. Also, umbilical cord blood lymphocytes produced IgM after stimulation with LPS, CW and PG. Coculture experiments with purified lymphocytes and monocytes indicated that B-cell differentiation was dependent on both T cells and monocytes, and that T-cell derived factors could derived factors could partially substitute for T cells. PMID- 3089919 TI - Anti-idiotype to monoclonal anti-swine SLA antibody detects a common idiotype shared by mouse anti-SLA sera and elicits an anti-SLA activity. AB - Heterologous anti-idiotypic reagents have been prepared against a BALB/c anti swine MHC (SLAd) monoclonal antibody (74-11-10) in order to test for possible interspecies idiotypic cross-reactions of anti-MHC antibodies. Using these reagents to examine xenoantisera produced in BALB/c mice immunized with swine SLAdd peripheral blood lymphocytes, all animals tested were found to express detectable levels of the 74-11-10 idiotype (Id). The Id could also be detected in one out of five BALB/c mice immunized with swine SLAcc PBL. Swine anti-SLAdd alloantibodies were also tested, but failed to show detectable levels of the 74 11-10 Id. The in vivo administration of anti-idiotypic reagents to BALB/c mice induced detectable levels of 74-11-10 Id positive antibodies that bound specifically to SLAdd PBL. Similar treatment of SLAgg swine (recombinant swine expressing the class I MHC molecules of c) with anti-idiotypic antibodies failed to induce anti-SLAd antibody activity. These results thus indicate that 74-11-10 represents a shared idiotype of BALB/c anti-SLAdd antibodies. The presence of 74 11-10 Id in one mouse immunized with SLAcc PBL suggests that the failure of pigs to express the 74-11-10 Id following treatment with anti-idiotypic antibodies may be the result of tolerance rather than absence of the relevant variable region gene(s). PMID- 3089921 TI - Gamma-interferon production by human low-density lymphocytes induced by T-cell mitogens. AB - Low-density lymphocytes prepared by Percoll fractionation of human peripheral blood mononuclear leucocytes were found to produce large amounts of interferon gamma (IFN-gamma) in response to different T-cell mitogens in the absence of macrophages, whilst higher density lymphocytes were strongly dependent on the presence of macrophages for significant IFN-gamma production. The addition of macrophages to the low-density lymphocytes made little difference to their IFN gamma production. Subsets of the low-density lymphocytes prepared by rosetting with sheep red blood cells produced markedly less IFN-gamma than did the original population; IFN-gamma production could be largely restored by recombining the two low-density fractions. This suggests that IFN-gamma production by low-density lymphocytes whilst macrophage-independent does require co-operation between different cell types. The low-density lymphocytes were enriched for cells bearing the Leu 11 and OKM1 antigens, and for natural killer cell activity. The rosetting fraction was enriched for OKT3 antigen-bearing cells, and the non-rosetting fraction was enriched for Leu 11, OKM1 antigen-bearing cells. Depletion of B cells (surface Ig-positive) by nylon-wool chromatography had no effect on IFN gamma production by low-density lymphocytes. PMID- 3089920 TI - Concanavalin A-stimulated rat spleen cells produce a soluble factor that supports growth of the mouse IL-3-dependent cell line Ea3.123, but not three other IL-3 dependent lines. AB - Several cloned, non-leukaemic mouse haemopoietic cell lines are believed to be uniquely dependent on interleukin-3 (IL-3) for their survival. All of these lines require the addition of WEHI-3B cell-conditioned medium for their growth. We have examined the growth requirements of four IL-3-dependent cell lines and found that only one, Ea3.123, is able to grow in medium conditioned by concanavalin A stimulated rat spleen cells (rat ConACM), whereas the other three, AC2, 32D cl-23 and FDC-P2, are not. Medium conditioned by the growth of concanavalin A stimulated mouse spleen cells (mouse ConACM) supports the growth of all four cell lines. The Ea3.123-supporting activity in rat ConACM appears to be of smaller size (approximately 27,000) than the activity in mouse ConACM and WEHI-3BCM (approximately 38,000). The activity is unlikely to be due to GM-CSF, since post endotoxin serum containing GM-CSF does not support growth of Ea3.123, nor is it likely to be IL-2, since we were able to remove IL-2 by absorption with CTLL-16 cells without affecting the ability of rat ConACM to support Ea3.123 cells. Our findings have important implications for the assay of IL-3, and mechanisms by which dependent cells respond to IL-3. PMID- 3089922 TI - The T-lymphocyte population in first-trimester human decidua does not express the interleukin-2 receptor. AB - The expression of the IL-2 receptor by T lymphocytes in human uterine decidua has been studied with two monoclonal antibodies to the IL-2 receptor employed in immunoperoxidase labelling of serial cryostat sections. Infiltrating T lymphocytes in early pregnancy decidua do not express the IL-2 receptor. Endometrial gland epithelium in early pregnancy showed unexpected reactivity with one of the mAbs to the IL-2 receptor (Tac). Thus, despite the close proximity of fetal trophoblast, macrophages and T-lineage lymphocytes in decidua in early pregnancy, IL-2 receptor-bearing lymphocytes are completely absent. PMID- 3089924 TI - EDTA-resistant activation of the terminal route of mouse complement after partial precipitation of serum with polyethylene glycol. AB - A new type of activation of the terminal route of complement is described. It occurs in precipitates of mouse serum prepared with a critical amount of polyethylene glycol. The activation proceeds in the presence of 10 mM EDTA and in the absence of C1q and functional C2, C3, C4 and factor B, which suggests that it is classical and alternative pathway-independent. The activation is demonstrated by the generation of both thermo-labile haemolytic and thermo-stable chemotactic activity. For both activities C5 seems to be essential. The haemolytic activity does not show species restriction towards sheep erythrocytes, which suggests a similarity with C56-initiated (reactive) but not with (S)C5-9-mediated (deviated) haemolysis. The identity of the haemolytic complex and the chemoattractant and the possible use of the new activation for the functional analysis of the mouse terminal complement route will be the subject of further study. PMID- 3089923 TI - Immunoglobulin synthesis in non-B cell lines. AB - A recombinant vector carrying rearranged immunoglobulin heavy (mu) and light (kappa) chain genes was introduced into several cell lines of non-B lineage including T cell (EL4) and two fibroblast lines (CV-1 and L cells). Our results indicated that intracytoplasmic mu-chains, both secretory and membrane types, were expressed in the recipient cell lines. Small amounts of kappa-chain transcripts, corresponding in size to authentic kappa-chain mRNA, were detected in EL4 and L cell transformants, whereas CV-1 transformants did not express the authentic kappa-chain RNA. EL4 and L cell transformants produced kappa-chain. This system will be quite useful for the analysis of regulatory mechanisms involved in immunoglobulin synthesis in non-B cells. PMID- 3089926 TI - Effects of Bacillus thuringiensis and insect pathogen, Pseudomonas aeruginosa, on mammalian gastrointestinal tract. PMID- 3089925 TI - Expression of the mid-stage differentiation B-cell antigen GP-70 in patients with early and stable form of B-CLL. AB - The expression of B-cell surface markers SmIg and GP-70 was determined on the mononuclear cells from the peripheral blood of 25 patients with chronic lymphocytic leukemia (CLL), 10 patients with multiple myeloma (MM), 6 normal blood donors and in 3 cases of unexplained persistent lymphocytosis. GP-70 was expressed only in CLL patients whereas multiple myeloma patients, blood donors and patients with unexplained lymphocytosis were all negative to GP-70. SmIg was expressed in CLL patients and in some of the multiple myeloma patients. Subgrouping of CLL patients to "early", stable patients (10) and to more advanced CLL patients (15) revealed differential expression of GP-70 on CLL cells from patients with more advanced stage of disease rather than in the patients with the "early" stable clinical course of disease. SmIg, on the other hand, was expressed equally on both subgroups of CLL. Furthermore, in some cases (25%) where SmIg and the light chains of Ig were only weakly expressed or were absent, GP-70 was markedly expressed. These findings suggest that GP-70 can be used as a single laboratory determination to establish clonality of the B-lymphocyte proliferation in CLL. In addition, expression of GP-70 correlates with significant clinical parameters of the disease. PMID- 3089927 TI - Possible involvement of adrenergic nervous system in anticonvulsant effect of lithium carbonate in albino rats. PMID- 3089928 TI - Lipofuscin pigment in laminae V and VI of the motor cortex of the 14 and 21 day old pups born to mothers induced to protein deficiency during pregnancy. PMID- 3089929 TI - Drug responses of S-180 tumours in syngeneic and xenogeneic hosts. PMID- 3089930 TI - Effect of selenium (selenite) on DNA and RNA synthetic activities in mouse liver, kidney and spleen following 7,12-dimethylbenz(alpha) anthracene administration. PMID- 3089931 TI - B-cell surface receptor differences in rhesus negative responders & non responders. PMID- 3089932 TI - Metabolic effect of aflatoxin B1 on the activity of drug-metabolizing enzymes & plasma level of marker enzymes of liver disorder in relation to nutritional stress. PMID- 3089933 TI - Comparison of living and nonliving vaccines for Brucella abortus in BALB/c mice. AB - The BALB/c mouse was selected as a model for infection with Brucella abortus on the basis of protracted nonclinical infection produced by strain 2308, virulent for cattle, and relatively rapid clearance of strain 19, an attenuated strain used to vaccinate cattle. Protection in mice vaccinated with strain 19 was compared with that obtained with nonliving vaccines at early (1 week) and later (4 weeks) intervals after challenge with strain 2308 and assessed by enumeration of B. abortus organisms in the spleen. Mice challenged 4 weeks after vaccination with strain 19 exhibited significant protection at 1 and 4 weeks postinfection (p.i.), with an increased magnitude of protection at the later time. When challenged 6 weeks after vaccination with strain 19, the level of protection diminished between 1 and 4 weeks p.i. and at the later time was not always significantly different from controls. Mice immunized 4 weeks earlier with nonliving vaccines in mineral oil with t trehalose dimycolate (TDM) and muramyl dipeptide (MDP) demonstrated patterns of protection similar to those obtained following the 6 week vaccination-challenge interval with strain 19. Vaccination with cell envelopes derived from strain 2308 produced equivalent protection at 1 week p.i. whether administered in phosphate-buffered saline, incomplete Freund adjuvant, or the TDM and MDP adjuvant. Equivalent protection also followed vaccination with strain 2308 killed whole cells, cell envelopes, or outer membrane proteins in phosphate-buffered saline or in the TDM and MDP adjuvant. The TDM and MDP adjuvant alone induced nonspecific resistance, which peaked at 1 day p.i. and was still present at 1 week p.i., although by this time its magnitude was significantly less than the protection induced by antigen combined with the adjuvant. These data, together with the results of antibody assays and passive and adoptive transfer studies, suggested that protection at 1 week p.i. could be accounted for largely by an effect of O antibodies, with T cell-mediated immune responses having a subsidiary role. PMID- 3089934 TI - Inhibition of the interaction of Streptococcus sanguis with hexadecane droplets by 55- and 60-kilodalton hydrophobic proteins of human saliva. AB - The effect of salivary secretions on the hydrophobicity of Streptococcus sanguis was investigated. Pretreatment of the bacteria with paraffin-stimulated whole saliva resulted in a 79% inhibition of adhesion to hexadecane droplets. Column chromatography on Sepharose 4B and sodium dodecyl sulfate gel electrophoretic analysis indicated that the inhibitory activity of saliva resided in a fraction containing material of approximately 60,000 molecular weight. The active components, which we have termed the hydrophobic components (HC), bind to octyl Sepharose beads. Pretreatment of S. sanguis with HC resulted in a dose-dependent inhibition of the streptococcus-hexadecane interaction that reached a maximum of 85%. Furthermore, HC effectively blocked the ability of S. sanguis to adhere to hydroxyapatite beads coated with either whole saliva or HC. Sodium dodecyl sulfate-polyacrylamide gel analysis indicated that HC eluted from octyl-Sepharose consisted primarily of two proteins (60 kDa and 55 kilodaltons) which could be resolved by high-pressure liquid chromatography. Both of these proteins were able to inhibit the binding of S. sanguis to hexadecane in a dose-dependent manner; however, the 60-kilodalton molecule was slightly more effective in this assay. Amino acid analysis of these proteins showed that both proteins contained a high percentage of nonpolar amino acids. These findings suggest that certain components of saliva influence the interaction of S. sanguis with hydrophobic surfaces. PMID- 3089935 TI - Arthropathic group A streptococcal cell walls require specific antibody for activation of human complement by both the classical and alternative pathways. AB - The induction of acute arthritis in rats by a single intraperitoneal injection of group A streptococcal cell wall is associated with the activation of complement. We have therefore investigated the interaction of arthropathic peptidoglycan polysaccharide complex of streptococcal cell walls and human complement. The incubation of cell wall in normal human serum results in the formation of complexes of cell wall and the C3 and C4 components of complement. Using agammaglobulinemic serum, we have further shown that the activation of complement and formation of complement-cell wall complexes absolutely requires the presence of a small quantity of specific antibody. This antibody is present in normal human immunoglobulin G and is effective as the Fab fragment (alternative pathway). Although antibodies specific for three cell wall epitopes were capable of inducing complement-cell wall complex formation by the classical complement pathway, only anti-A polysaccharide antibody (N-acetyl-D-glucosamine epitope) was effective by the alternative complement pathway. A complement consumption assay showed that anti-cell wall antibody was required not only for complement-cell wall complex formation, but also for activation of complement by streptococcal cell wall in human serum. These studies suggest that a minimal level of anti-cell wall antibody may be required for the induction of arthritis in rats by streptococcal cell wall. PMID- 3089936 TI - Induction of tryptophan catabolism is the mechanism for gamma-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells. AB - Human uroepithelial (T24) cells were incubated for 24 h in the presence of various concentrations of human recombinant gamma interferon (Hu-rIFN-gamma) and then infected with the 6BC strain of Chlamydia psittaci. This resulted in a reduction of intracellular chlamydial inclusion development in proportion to the concentration of Hu-rIFN-gamma present when Giemsa-stained cells were examined by light microscopy 24 h after infection. When tryptophan was added to Hu-rIFN-gamma treated cells just after infection, reversal of the Hu-rIFN-gamma-mediated inhibition occurred in proportion to the concentration of tryptophan added. Addition of either isoleucine or lysine did not result in reversal of the antichlamydial state. Transport of L-[3H]tryptophan into acid-soluble intracellular pools was found to be greatly enhanced in Hu-rIFN-gamma-treated T24 cells compared with the rates measured for untreated cells. Transport of [3H]leucine was not increased in treated cells. Cells treated with Hu-rIFN-gamma also degraded L-[3H]tryptophan to catabolites that cochromatographed with N formylkynurenine and kynurenine as measured by high-performance liquid chromatography. We conclude that Hu-rIFN-gamma-mediated inhibition of intracellular C. psittaci replication in T24 cells occurs by depletion of the essential amino acid tryptophan, most likely via the induction of indoleamine-2,3 dioxygenase, the initial enzyme of tryptophan catabolism. PMID- 3089937 TI - Biological effects of anti-lipid and anti-protein monoclonal antibodies on Mycoplasma pneumoniae. AB - Monoclonal antibodies directed against Mycoplasma pneumoniae surface components were examined for their ability to block mycoplasma attachment to chicken erythrocytes. Purified preparations of antibodies which recognize the major mycoplasma ligand mediating cytadherence (protein P1, 165 kilodaltons) inhibited attachment by more than 85% of the control values. Monoclonal antibodies reactive with two other surface proteins of 110 and 32 kilodaltons also blocked attachment. Surprisingly, monoclonal antibodies specific for M. pneumoniae lipids (J. Morrison-Plummer, D. H. Jones, and J. B. Baseman, J. Immunol. Methods 64:165 178, 1983) enhanced mycoplasma-erythrocyte binding. All antibodies examined had no effect on thymidine incorporation by M. pneumoniae. PMID- 3089938 TI - Antibody determinations by counterimmunoelectrophoresis in the diagnosis and management of Pseudomonas aeruginosa bone and joint infections. AB - Antibody titers were measured by counterimmunoelectrophoresis in eight patients with Pseudomonas aeruginosa and in eight patients with Staphylococcus aureus bone and joint infections. Titers were obtained at the beginning of therapy in all patients with pseudomonas infections and at various intervals during and after completion of therapy in seven patients. These patients were followed clinically, with 99mTc-MDP bone and 67Ga scans, and with serial erythrocyte sedimentation rates. Six of eight of these patients had detectable pseudomonas antibodies. A fall in antibody titer occurred in all six successfully treated antibody-positive patients. By contrast, none of the control patients with staphylococcal infections had antibodies to pseudomonas heptavalent antigen. The predictive value of a positive test was 100% and of a negative test, 80%. Counterimmunoelectrophoresis is a helpful adjunctive test in supporting the diagnosis and documenting a successful treatment of chronic pseudomonas bone or joint infections. PMID- 3089939 TI - Laminar air flow isolation and decontamination: a prospective randomized study of the effects of prophylactic systemic antibiotics in bone marrow transplant patients. AB - 122 patients with hematologic malignancies underwent allogeneic marrow transplantation from HLA-matched sibling donors and received one of two forms of infection prophylaxis while granulocytopenic: 1) decontamination and laminar air flow isolation (LAF, 68 patients), and 2) LAF plus prophylactic systemic antibiotics (LAF + PSA, 54 patients). Patients were evaluated for infection acquisition while in isolation. Septicemia occurred in 11 (16%) of the patients in the LAF group and in three (6%) patients in the LAF + PSA group. Fourteen (21%) of the patients in the LAF group and four (7%) patients in the LAF + PSA group had a major local infection. There was no difference in the incidence and severity of graft-versus-host disease or incidence and duration of fever. The addition of prophylactic intravenous broad-spectrum antibiotics for patients isolated in LAF rooms significantly decreased infection acquisition. PMID- 3089940 TI - Is aciclovir prophylaxis necessary after bone marrow transplantation? AB - To assess the cost-effect relationship of aciclovir prophylaxis versus early treatment, we performed a retrospective study in 44 allogeneic bone marrow transplant recipients, who had only received aciclovir for therapeutic purposes. After bone marrow transplantation 18 herpes simplex infections occurred in 15 of the 33 patients who were seropositive for herpes simplex virus. In ten patients without clinical signs, routine viral cultures yielded herpes simplex virus. Aciclovir was given intravenously to the patients with mucocutaneous herpes infection. All infections responded rapidly. It can be calculated that restricting the drug to therapeutic use reduced the amount of aciclovir used, which in turn diminished the cost of treatment and the risk of aciclovir resistance. PMID- 3089941 TI - Impact on peritonsillar infections and microflora of phenoxymethylpenicillin alone versus phenoxymethylpenicillin in combination with metronidazole. AB - In a double-blind study, 20 patients with peritonsillar abscesses were treated with 2 g phenoxymethylpenicillin b.i.d. for ten days together with needle aspiration, incision and daily drainage, and 20 patients were treated with 2 g phenoxymethylpenicillin b.i.d. and 0.8 g metronidazole b.i.d. for ten days together with needle aspiration, incision and daily drainage. Group A beta hemolytic streptococci were isolated from pus in 20 of the patients with peritonsillar abscesses, in five of these together with indigenous oropharyngeal aerobic and anaerobic microorganisms. Pure anaerobic bacteria were found in nine abscesses, together with indigenous aerobic microorganisms in eight, and together with group A, C and G streptococci in five. In one patient heavily colonized with beta-lactamase-producing Staphylococcus aureus, Haemophilus parainfluenzae and Bacteroides, group A beta-streptococci failed to be eradicated. In the penicillin group, nine of 18 patients harboured beta-lactamase producing Bacteroides strains in the tonsils on the day of admission. On the third and tenth days of treatment all patients harboured beta-lactamase producing Bacteroides strains in the tonsils, while in the penicillin + metronidazole group, only one out of 17 patients still harboured beta-lactamase producing Bacteroides strains. None of the patients harboured beta-lactamase producing fusobacteria on the day of admission. In the penicillin group, however, beta-lactamase producing fusobacteria were recovered from three patients on the tenth day of treatment. No beta-lactamase producing fusobacteria were recovered from the penicillin + metronidazole group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3089943 TI - Effect of some proliferative and environmental factors on the toxicity of mitomycin C to tumor cells in vitro. AB - Mitomycin C (MC) was more toxic to EMT6 mouse mammary tumor cells in vitro under hypoxia than under aerobic conditions. This was evidenced both in survival curves defining the toxicity of treatment with a constant dose of MC given for different periods of time and in survival curves defining the effect of a 1-hr treatment with different concentrations of MC. Cultures preincubated for different periods from 1 to 6 hr in hypoxia all had similar MC sensitivities. In contrast, cultures preincubated in hypoxia for 4 hr then "reoxygenated" before MC treatment had the same sensitivities as cultures which had never been hypoxic. This shows that the oxygenation at the time of MC exposure, rather than the preincubation protocol, was the parameter determining cell sensitivity. Exponentially-growing (proliferating) and plateau-phase (quiescent) cultures had similar MC survival curves; neither type of culture repaired potentially lethal damage when held for up to 24 hr in HBSS after MC treatment. The sensitivity of the cells increased as the pH of the culture medium was decreased to low values (pH 7.0-6.0), but extracellular pH had no significant effect on the cytotoxicity of MC over the physiologic range (7.0-7.4). These data suggest that differences in the metabolic characteristics of cells that are hypoxic and aerobic during MC treatment, rather than perturbations of the cell proliferation patterns, the PLDR capacity of the cells, or the extracellular pH during the hypoxic incubation, are responsible for the different sensitivities of aerobic and hypoxic cells to MC in vitro. PMID- 3089942 TI - Wound infection following dog bite despite prophylactic penicillin. AB - Dog bite wounds of 39 children (ages one to 16 years) were cultured and irrigated. Cultures showed various organisms but were of no predictive value for development of infection. By using a table of random numbers, patients were assigned to either oral penicillin V-K (100,000 U/kg/day every 6 h) or placebo for two days. All patients were seen in follow-up in three to four days and again at seven to 10 days or earlier if signs of inflammation occurred. The mean patient age, location and type of wound, and initial wound care were similar in the two treatment groups. Three of 39 (7.7%) children enrolled in the study developed infection at the bite site, including two of 19 in the penicillin group and one of 20 in the placebo group. In our study, prophylactic penicillin failed to prevent infection in dog bite wounds. Good local care on presentation seems to be the most important factor in determining future infection. PMID- 3089944 TI - Red blood cell polyamine levels and host toxicity during continuous alpha difluoromethylornithine infusion. AB - The dose effects of continuous alpha-difluoromethylornithine (DFMO) infusion on red blood cell (RBC) polyamine levels, host toxicity and tumor growth were determined. Male rats with and without a transplantable methylcholanthrene induced sarcoma received intravenously either 0.45% NaCl or DFMO at 500 mg, 1,000 mg, or 2,000 mg/kg body wt/day for 6 or 12 days. Dose-related inhibition of tumor growth was noted after the 12-day treatment. There were no changes in host carcass weight, food intake, plasma albumin, hematocrit or white blood cell counts. Platelet suppression was associated with the 1,000- and 2,000-mg doses with the 12-day treatment. Morphometry of the small intestine revealed mild but significant shortening of villi in the duodenum and jejunum at the 2,000-mg dose, but none of the animals developed diarrhea. The 500-mg DFMO dose reduced the rate of tumor growth without inducing platelet suppression or altering intestinal morphology. A decrease in RBC putrescine levels was noted at all doses. RBC spermidine levels increased with the 500-mg dose. RBC spermine levels were higher at all doses compared with controls. These results suggest that thrombocytopenia is the major dose-limiting side-effect of continuous DFMO infusion but does not occur at a dose of 500 mg/kg body wt/day. PMID- 3089946 TI - Treatment with preparations of human leukocyte interferon decreases serum testosterone concentrations in men. PMID- 3089945 TI - Effect of Fluosol-DA/O2 on tumor-cell and bone-marrow cytotoxicity of nitrosoureas in mice bearing FSA-II fibrosarcoma. AB - The perfluorochemical emulsion, Fluosol-DA, combined with carbogen breathing, potentiates the effects of radiation and a number of chemotherapeutic agents in several rodent tumors. The interaction of Fluosol-DA with drugs may be quite complex. In addition to increasing the oxygen supply in the tumor, Fluosol-DA may alter the pharmacokinetics of the drug and function as a drug delivery system. A series of 4 nitrosoureas of varying lipophilicity were administered as single doses intravenously (i.v.) to C3H/Be/FeJ mice bearing subcutaneous FSa-IIC fibrosarcomas. Doses of 40 mg/kg of CCNU, 15 mg/kg of BCNU, 20 mg/kg of MeCCNU and 15 mg/kg of chlorozoticin followed by 2 hr of breathing 95% oxygen produced tumor growth delays of 7.5, 4.0, 3.8 and 2.7 days, respectively. When the drug injection was followed immediately by 0.3 ml of Fluosol-DA and 2 hr of breathing 95% oxygen, the tumor growth delay produced by CCNU, BCNU, MeCCNU and chlorozoticin increased 2-fold, 10-fold, 4.5-fold and 3.5-fold, respectively. Administration of the drugs in Fluosol-DA followed by 2 hr of 95% oxygen breathing resulted in a 3.5-fold increase in tumor growth delay with CCNU, a 17 fold increase with BCNU, a 12.5-fold increase with MeCCNU and a 6-fold increase with chlorozoticin compared to drug and 95% oxygen breathing. These results are quantified in terms of cell survival by the tumor excision assay. Effects on the bone marrow from each treatment were measured using the granulocyte-monocyte colony-forming units (CFU-GM) assay. There was no correlation between the lipophilicity of the nitrosoureas tested and the tumor growth delay produced by each treatment. PMID- 3089947 TI - Nitrate tolerance. AB - Nitrates are widely used in anginal prophylaxis. In spite of the fact that the concept of nitrate tolerance was first put forward many years ago, the question of tolerance has remained controversial. There is widespread agreement that tolerance does occur to the effects of nitrates on arterial pressure. In contrast, tolerance to the venous and pulmonary effects is disputed. Similarly, the possibility of tolerance to the antianginal effects remains at issue. In this review, I discuss the factors which may have contributed to conflicting results in different studies, in particular recent findings on the rapidity of onset and reversal of tolerance. Tolerance develops rapidly on initiation of treatment and disappears equally rapidly on its discontinuation. In addition, tolerance appears to be a function of plasma nitrate profile. It is most likely to occur when plasma nitrate levels are constant and least likely when nitrate levels fluctuate. Furthermore, the provision of a daily nitrate free interval may protect against the development of tolerance. I then discuss the implications of these findings for patient management. They suggest that nitrate prophylaxis should not be used continuously, if this can be avoided. Rather, prophylaxis should be tailored to the individual to provide protection at times of maximum susceptibility, while allowing nitrate levels to fall at other times. The adequacy of antianginal protection with drug regimens incorporating a nitrate free interval requires further assessment. Similarly, the possibility that a nitrate free interval might lead to withdrawal effects and exacerbation of angina needs to be excluded. PMID- 3089948 TI - The use of impedance cardiography in heart failure. AB - The suitability of the impedance cardiograph for studying patients with cardiac failure in a District General Hospital was assessed over a 12-month period. Over 200 recordings were made from 60 patients. Stroke volume, using the derived formulation of Kubicek and his colleagues, and the Heather Index (a measure of cardiac contractility) were calculated in each case. Serial recordings provided an objective assessment of the efficacy of treatment. An abnormal diastolic O wave was found in the majority of patients. This may indicate an excessive accumulation of blood in the thorax as a result of myocardial dysfunction. PMID- 3089949 TI - Absorption and disposition kinetics of lithium carbonate following administration of conventional and controlled release formulations. AB - The absorption and disposition kinetics of lithium carbonate administered to eight healthy volunteers in two dosage forms were studied. A conventional immediate release tablet and a controlled release preparation, developed in our laboratory and containing the drug into a hydrophilic matrix, were employed in the study. Lithium carbonate confers upon the body the distinct characteristics of a two-compartment open model with a mean slow disposition rate constant (beta) of 0.0435 h-1 +/- 0.0086 SD, corresponding to a mean biological half-life of 16.49 h +/- 2.95 SD. The mean half-life of the distributory alpha-phase was 1.40 h +/- 0.27 SD. The apparent volume of distribution (Vdarea) was 0.539 l kg-1 +/- 0.130 SD and the volume of the central compartment (Vl) was 0.224 l/kg-1 +/- 0.066 SD, about one half that of the volume at steady state (Vdss) which was 0.445 l/kg-1 +/- 0.106 SD. Total body clearance (ClB) was 0.0241 l/kg-1 h +/- 0.0102 SD. The administration of the controlled release preparations to the same subjects gave the expected smooth serum lithium concentration curves. Maximum serum concentration (Cmax) was 22% lower and the time at which this concentration was attained (tpeak) was delayed from 1.44 h to 4.25 h when compared with the conventional tablet. Bioavailability, estimated as the total amount of lithium excreted in the urine, was 90.2 for the controlled release preparation and 94.5 for the immediate release tablet. PMID- 3089950 TI - Serum levels and pharmacokinetics of ordinary and sustained-release lithium carbonate in manic patients during chronic dosage. AB - Ordinary and sustained-release lithium carbonate were administered at approximately equivalent daily dosage (1.5 and 1.8 g = 20.2 and 24.3 mmol ordinary and sustained-release respectively) in a crossover fashion to 5 manic patients. Actual and theoretical steady state serum levels of both preparations were determined. The sustained-release preparation gave observed serum levels that differed widely from predicted levels. Despite larger inter and intra subject variations the serum levels at commencement and end of the sampling period were fairly constant. The results suggest that the wide individual variations in steady state profiles may be a consequence of the effect of normal physiological variables on drug absorption in the patient/sickness/diet combination of this study. Apparent erratic absorption in some patients, especially with the sustained-release preparation, indicates that great caution should be exercised in deciding when to monitor serum levels as a guide to adjusting dose. A justification is presented for morning sampling time as the most appropriate, regardless of the type of formulation used. PMID- 3089951 TI - Inhibition by lysine and arginine of the conversion of C3 and B in the serum and a purified system. AB - When human serum was incubated at 45 degrees C for 30 min, C3 and B were converted to C3b and Bb. Molecular weights of purified C3 and B were shown not to change after incubation at 50 degrees C. Spectropolarimetry indicated that the secondary structures of C3 and B changed after incubation at higher temperature. The titration of SH groups in the C3 molecule showed the liberation of an SH group. These results show that the alternative complement pathway is activated at raised temperatures without known activators such as zymosan or lipopolysaccharide (LPS). This may be due to the accelerated interaction of conformationally changed components of the alternative pathway such as C3 and B. Using this system, effects of various substances on the interaction of C3 and B in serum and the purified system were investigated. The addition of arginine and lysine resulted in the inhibition of the conversion of C3 and B in the serum at elevated temperature. Other amino acids such as anionic amino-acids and NaCl did not influence the conversion. In the purified system, only arginine and lysine prevented the conversion of C3 and B, when C3, B and D were incubated in the presence of Mg++ and amino-acids. Since lysine and arginine did not inhibit the enzymatic activity of D, these data suggest that arginine and lysine prevent the interaction of C3 and B in the serum at elevated temperatures. PMID- 3089952 TI - Cyclooxygenase inhibitors promote the leukotriene C4 induced release of beta glucuronidase from rat peritoneal macrophages: prostaglandin E2 suppresses. AB - The effects of leukotriene C4, indomethacin, aspirin and prostaglandin E2 on macrophage activity were investigated, whereby the release of the lysosomal enzyme beta-glucuronidase was taken as a criterion for cell activity. Leukotriene C4 enhanced the release of beta-glucuronidase as well as the production of prostaglandin E2. Blocking the production of endogenous prostaglandins by adding indomethacin or aspirin resulted in an augmented effect of leukotriene C4. Exogenous prostaglandin E2 could reverse the leukotriene C4 and/or indomethacin induced beta-glucuronidase release. These results support the postulated interaction between leukotriene C4 and prostaglandin E2 with respect to the regulation of macrophage activity, leukotriene C4 being stimulatory, prostaglandin E2 suppressive. PMID- 3089953 TI - Immunopharmacological study of CCA (Lobenzarit disodium), an anti-arthritis agent -I. Abrogation of IL 1 secretion by LPS-stimulated human monocytes and induction of gamma-interferon production with CCA. AB - In vitro effects of CCA, an anti-arthritis agent, were studied upon autologous mixed lymphocyte reaction (AMLR), lymphocyte mitogenesis, IL 1 and IL 2 production, immunoglobulin production and gamma-interferon (IFN) production. CCA at 50 micrograms/ml, which was not toxic to cells, blocked AMLR, IL 1 production and immunoglobulin production (IgM and IgG) significantly, while CCA at the same dose did not affect IL 2 production and lymphocyte mitogenic responses to Staphylococcus aureus Cowan I(SAC) and pokeweed mitogen(PWM). CCA at both 20 ng/ml and 20 micrograms/ml induced human gamma/IFN. Addition of IL 1 and/or IL 2 reversed inhibitory effect of CCA on AMLR. These data suggest that CCA exerts its actions by mainly affecting T cells and monocytes and can be used as an immunomodulator. PMID- 3089954 TI - Enhancement of murine lymphoma cell lysability by CTL and by LAK cells, after treatments with mitomycin C and with adriamycin. AB - Murine lymphoma cells (RDM4) were treated, in culture, with adriamycin (ADM) and with mitomycin C (Mit C) at various concentrations for 20 h. They were then used as 51Cr-labelled target cells and tested for their sensitivity to the killing action both of specifically allosensitized cytotoxic T lymphocytes (CTL) and of lymphokine-activated killer (LAK) cells. They were also used as "cold target" inhibitors, in cytotoxicity assays involving CTL or LAK and 51Cr-labelled target cells. The results showed that treatments with different concentrations of Mit C enhanced the sensitivity of RDM4 cells to the killing actions of both CTL and LAK cells. ADM slightly enhanced sensitivity to the killing action by CTL, but to a much lesser extent than Mit C did. However, ADM proved to be almost as efficient as Mit C in its sensitizing action, in the case of lysis by LAK cells. Treatments with both drugs did not seem to modify the capacity of RDM4 cells to act as "cold target competitors" in cytotoxicity assays involving CTL killers, but did so in experiments involving the lytic action exerted by LAK cells. PMID- 3089955 TI - Socialized medicine: a solution to the cost crisis in health care in the United States. AB - Despite growing concern with cost containment, most health policy analysts have ignored vast potential savings on medically irrelevant spending for excess administration, profits, high physician incomes, marketing, and legal involvement in medicine. Indeed, many recent reforms encourage administrative hypertrophy, entrepreneurialism and litigation. A universal national health program could abolish billing and consequently the need for much of the administrative apparatus of health care, and decrease spending for profits and marketing. In this article we analyze the administrative savings that could be realized from instituting a Canadian-style national health insurance program or a national health service similar to that in Britain, and the potential savings from additional reforms to curtail profits, marketing and litigation. Our calculations based on 1983 data suggest that national health insurance would save $42.6 billion annually: $29.2 billion on health administration and insurance overhead, $4.9 billion on profits, $3.9 billion on marketing, and $4.6 billion on physician's incomes. A national health service would save $65.8 billion: $38.4 billion on health administration and insurance overhead, $4.9 billion on profits, $3.9 billion on marketing, and $18.6 billion on physician's incomes. Complete nationalization of all health related industries and reform of the malpractice system would save at least $87.2 billion per year. We conclude that a national health program, in addition to improving access to health care for the oppressed, could achieve cost containment without rationing of care. PMID- 3089957 TI - Comparison of the anaerobic threshold and mechanical efficiency of running in young and adult athletes. AB - We determined noninvasively in a laboratory on the treadmill the anaerobic threshold (AT) (ventilatory threshold) and mechanical efficiency (ME) of running in 7 adult male long-distance runners (mean age = 24.1 yrs) and 17 adolescents (17.0 yrs), in 8 adult female middle-distance runners (23.2 yrs), in 12 young (16.1 yrs) and in 28 adult male canoeists (22.8 yrs), and in 10 juniors (17.4 yrs). We did not find significant differences in the metabolic adaptation characterized with the help of % VO2max on the AT level between relatively equally trained juniors and adults. In long-distance runners the % of VO2max on the AT level was 85.3% for adults and 85.2% for adolescents, in female middle distance runners 82.8% and 82.7%, respectively, in adult canoeists 78.9%, and in juniors 79.8%. In ME which characterizes the degree of adaptation to the running and depends on the years of training and thus on the differences in racing performance, the values were lower for young athletes than for adults. The ME found in long-distance runners was 25.4% for young athletes and 32.4% for adults, in middle-distance runners 28.4% and 30.3%, respectively, and in canoeists 24.5% and 26.7%, respectively. The difference was significant only in long-distance runners where the greatest difference in racing performance (about 15%) is also found. The close similarity in responses to submaximal work intensities in adults and young sportsmen or subjects of equivalent fitness suggests caution in the interpretation of agewise decrements observed in physiologic variables which may be sensitive to physical fitness status. PMID- 3089956 TI - Use of essential drugs in rural Ghana. AB - In this article, a drug utilization study in 15 district hospitals and 2 health centers in Ghana is described. Use of 94 essential drugs was measured over 2.5 million treatment episodes during 1981-1982. It was found that much less is spent on drugs in health centers than in hospitals, expressed in cost per 10,000 treatment episodes. In hospitals with Ghanaian doctors, about twice as much is spent on drugs as in hospitals with expatriate doctors. Particular therapeutic groups and drugs for which larger quantities are used are also analyzed. Possible reasons for and consequences of these differences are discussed. The results of this study form the most reliable records currently available on drug utilization in Ghana. They record the actual drug use, that is, the total drug use within existing patterns of prescription and losses. These figures have been used for a consumption-based estimate of drug requirements for 64 church-related district hospitals and health centers. PMID- 3089958 TI - Synthesis of N3-fumaramoyl-L-2,3-diaminopropanoic acid analogues, the irreversible inhibitors of glucosamine synthetase. AB - Several analogues of N3-fumaramoyl-L-2,3-diaminopropanoic acid were synthesized and evaluated for inhibition of glucosamine-6-phosphate synthetase activity. The syntheses were accomplished by acylation reaction of N2-tert.-butoxycarbonyl-L 2,3-diaminopropanoic acid (Boc-A2pr) or N2-tert.-butoxycarbonyl-L-2,4 diaminobutanoic acid (Boc-A2-bu) with the N-succinimidoyl esters of several derivatives of alpha, beta-unsaturated acids 2a-d followed by deprotection of the Boc groups. The obtained compounds were tested for inhibition of glucosamine synthetase isolated from Salmonella typhimurium and Saccharomyces cerevisiae. The results indicated that among the synthesized compounds, N3-4-methoxyfumaroyl-L 2,3-diaminopropanoic acid (FMDP) was the most powerful inhibitor of glucosamine synthetase. PMID- 3089959 TI - Conformational study of thyrotrophin-releasing hormone. I. Aspects of importance in the design of novel TRH analogues. AB - The solution conformations of thyrotrophin-releasing hormone (TRH), a biologically-active tripeptide, have been predicted computationally using a method which represents solution effects as a dielectric continuum surrounding the molecule throughout energy minimisation; this is described as the reaction field contribution. The predicted conformations have been compared with previous experimental and theoretical studies. Favoured conformations of TRH under other simulated conditions have also been examined, including the behaviour of the cis isomer, and have been related to possible interactions with intermediates and with specific receptors. The relevance of these predictions to the design of biologically-active analogues of TRH has been analysed. PMID- 3089960 TI - Effects of hyperthermia on radiation-induced chromosome breakage and loss in excision repair deficient Drosophila melanogaster. AB - Hyperthermia increased radiosensitivity with respect to gamma-ray induced chromosome loss and breakage in all stages of spermatogenesis in the wild type Oregon R strain of Drosophila melanogaster, whereas hyperthermia increased radiosensitivity to a lesser extent in cn mus (2) 201D1, an excision repair mutant with 0 per cent excision capacity and in mus (3) 308D1, a strain with 24 per cent excision capacity. The differences in hyperthermia-induced radiation sensitivity between the excision repair mutants and the wild strain may be due to the hyperthermia affecting the excision repair mechanism, suggesting that one of the possible mechanisms involved in hyperthermia-increased radiosensitivity is an effect on excision repair. PMID- 3089961 TI - Rhodium(III) as a potentiator of the effects of X-rays on cells. AB - A rhodium compound, Rh(NH3)3Cl3, does not sensitize the spores of Bacillus megaterium to X-rays. However, it is a very effective sensitizer of vegetative cells of Staphylococcus aureus, raising the sensitivity four times in O2 and over 100 times in anoxia. The inhibition by oxygen of the sensitizing action of Rh(III), which operates over a wide range of [O2], is noteworthy. These experiments were performed in saline-phosphate buffer using 50 kVp X-rays. The results are discussed in terms of the known radiation chemistry of this compound. PMID- 3089962 TI - [Therapy of acute heart failure]. PMID- 3089963 TI - Perturbations in cancer cell deformability and resistance to shear forces. AB - During hematogenous metastasis, circulating cancer cells appear to be killed in the microcirculation by a non-exclusive mechanism, involving the mechanical trauma consequent upon cancer cell interactions with the vessel wall. Various observations by others indicate that with increased cell deformability, there is decreased intravascular cell killing. We have therefore critically examined the effects of agents previously shown to modify cell deformability, on the susceptibility of Ehrlich ascites tumor and L1210 leukemia cells to mechanical damage on passage through polycarbonate membranes in vitro. Treatment with neuraminidase, trypsin or EGTA, was previously shown to increase cell deformability. However, in the present studies, neuraminidase treatment was associated with increased cell loss on filtration; trypsin treatment with small decreases in cell loss, and EGTA treatment with decreased loss. Consideration of the effects of these agents on cell deformability and membrane strength suggests that under the described experimental conditions, the latter appears more important for survival than the former. As proteolytic and glycolytic enzymes and calcium ions are involved in the release of cancer cells from tumors and invasive events, the effects described here may be relevant to the variability of cancer cells with respect to the metastatic process. PMID- 3089964 TI - Topical prostaglandins inhibit trauma-induced inflammation in the rabbit eye. AB - Topical administration of prostaglandin E1 (PGE1) and prostaglandin F2 alpha (PGF2 alpha) prior to ocular trauma can reduce the ocular inflammatory response in rabbits. In the present study, the ocular trauma consisted of puncture of the cornea, without aspiration of aqueous. Corneal puncture, which causes and inflammatory response, a breakdown of the blood-aqueous barrier, and a biphasic response of the intraocular pressure (IOP), yields a valid model of a mild inflammatory response. Pretreatment with PGE1 and PGF2 alpha led to a lower rise in the aqueous prostaglandin E2 (PGE2) concentration and a reduced inflammatory response after corneal puncture; in addition, the increase in the aqueous protein concentration was smaller and the aqueous ascorbate level was higher. The lower increase in the aqueous PGE2 concentration after pretreatment with PGs correlated with the reduced changes in IOP. It is suggested that PGE1 and PGF2 alpha reduced the trauma-induced inflammatory response by decreasing the formation of endogenous prostaglandins, as reflected by their concentration in aqueous. This study also indicates that the results of studies that require perforation of the cornea or cannulation of the anterior chamber may be affected by profound changes in the levels of cyclo-oxygenase products in the tissues surrounding the aqueous. PMID- 3089965 TI - Lymphoma allografts abrogate immune privilege within the anterior chamber of the eye. AB - Immune privilege is extended to allogeneic tissues placed into the anterior chamber of the eye and results in part from the induction of anterior chamber associated immune deviation (ACAID)--a condition in which the host is capable of making humoral antibodies and cytotoxic T cells specific for the antigens in question, but is selectively suppressed in its capacity to generate delayed-type hypersensitivity (DTH). Privilege is extended only transiently to tissue differing at the major histocompatibility complex; by contrast, privilege is complete for tissues offering multiple minor H incompatibilities, but no MHC disparity. During examination of host responses to tumor cell lines in this latter category, it was observed that privilege was extended to all histologic categories of tumors examined except T cell lymphomas. Moreover, the capacity of minor H incompatible tumors to maintain immune privilege and sustain prolonged survival within the anterior chamber could be abrogated if T cell lymphomas were placed into the anterior chamber of the contralateral eye. Thus, T cell lymphomas exert a systemic influence which robs the anterior chamber of its immune privilege. It is concluded that this systemic effect is intimately related to lymphokines produced by T cell lymphoma allografts. Since immune privilege seems to be a physiologic property of the anterior chamber, it is suspected that local features within this site conspire to insure that antigens placed therein interact with the immune system in a manner that bypasses lymphokine production, thus allowing for the induction of ACAID and selective suppression of DTH. PMID- 3089966 TI - Serum levels of sodium valproate, phenytoin and carbamazepine and seizure control in epilepsy. PMID- 3089967 TI - Using DRGs for competitive positioning and practical business planning. AB - For hospitals to survive in today's highly competitive environment, administrators must understand their markets and develop products and services more appropriate to the demands of their customers. DRGs can be seen as individual products, and can serve as the basis for practical business planning. PMID- 3089969 TI - [Contact dermatitis caused by 2-chloroacetophenone following tear gas exposure]. AB - We report a case of acute contact dermatitis caused by exposure to 2 chloracetophenone tear gas in the face. Within 3 days the contact dermatitis had disappeared without medical treatment, but 7 days after exposure, a scaly pruritic eruption developed at the site of the original exposure although no new contact with 2-chloracetophenone had taken place. PMID- 3089968 TI - Full cost determination: an application of pricing and patient mix policies under DRGs. AB - Prospective payment systems have replaced retrospective reimbursement, thus increasing the need to determine costs, income, and potential losses in order to adjust the patient mix so as to minimize losses and maximize profits. Three phases in applying pricing and patient mix policies are described. PMID- 3089970 TI - Use of nursing homes by a high-risk long-term care population. AB - Limited information exists concerning lifetime use of nursing home services by the aged. This article examines the longitudinal experience, over four years, of elderly individuals at high risk of institutionalization, and develops a simple model of nursing home use based on these observations. This model allows us to predict future lifetime use under alternative assumptions. The main observations drawn from this sample are that high-risk elderly tend to move from the community to nursing homes, but not back to the community except for short, transitional stays. Further, despite high overall mortality rates, the expected nursing home use by these high-risk elderly is very high, due to long average stays by a minority of the sample that enters a nursing home and remains there longer than six months. PMID- 3089971 TI - A density threshold for the expression of longevity in Drosophila melanogaster. AB - Long- and short-lived strains, selected for longevity for up to 27 generations, were raised under two treatments of developmental density. Selected stocks, controls and F1 crosses between them are respectively long-lived, short-lived and intermediate, when raised at a high and uncontrolled developmental density. But when development takes place at a low density, longevity is sharply reduced, showing the existence of a developmental-density threshold for the expression of long life in selected strains and crosses. Selection for longevity is shown to have had effects in males comparable with those in females in the long-lived stock and in reciprocal F1 crosses with the short-lived control. No age-specific effects on longevity were found in progeny from young, middle-aged and old adults. PMID- 3089972 TI - Controlled growth of colloidal gold particles and implications for labelling efficiency. AB - A new method is reported for the preparation of colloidal gold particles with diameters ranging between 5 and 12 nm. The initial gold particle population, with an average diameter of 5.6 +/- 0.9 nm, is prepared by reduction of chloroauric acid with white phosphorous. An increase in particle diameter by growth is obtained by reduction of chloroauric acid with white phosphorous in the presence of colloidal gold particles. The labelling efficiency of these gold particles, conjugated with protein A, in indirect immunolabelling experiments is investigated by labelling of beta-galactosidase on ultrathin cryosections of Escherichia coli cells. We demonstrate that the labelling efficiency is at least dependent on particle diameter, probe concentration and preparation method. In addition it is shown, that with this new method, gold particle populations can be prepared with minor overlap in diameter spreading. Therefore these gold probes are suitable for qualitative double labelling experiments. The quantitative aspect of immunolabelling is discussed. PMID- 3089973 TI - Detection of 2-amino-3-methylimidazo[4,5-f]quinoline in cigarette smoke condensate. AB - 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), which is mutagenic and carcinogenic, was found to be present in cigarette smoke condensate by liquid chromatography with an electrochemical detector and a photodiode-array detector. The amount of IQ was estimated to be 0.26 ng per cigarette. PMID- 3089974 TI - Testosterone in infant testis yolk sac tumor indicating a mixture of germ cell and sex cord/stromal elements: a new concept. AB - The presence of testosterone in yolk sac tumor of the infant testis was investigated immunohistochemically. All 16 cases tested were positive for the hormone. The antigen-positive tumor cells were primitive mesenchymal cells and columnar cells forming small ducts, which resembled Leydig cells and Sertoli cells, respectively. These cells accounted for about 1 to 20% of tumor cells and were intermingled with typical yolk sac structures. In contrast, no yolk sac tumor of adult testis was definitely positive for the antigen. In view of its distinctive histological and immunohistochemical features and clinical behavior, yolk sac tumor in the infant testis is most likely a separate and specific entity, composed of a mixture of germ cell and sex cord stroma derivatives. PMID- 3089975 TI - Some cardiotonics enhance the effectiveness of angiotensin II-induced hypertension cancer chemotherapy in mice. AB - Angiotensin II-induced hypertension chemotherapy proved to be more effective than conventional chemotherapy using cis-diamminedichloroplatinum (II) (DDP), when applied to an established mouse mammary carcinoma. In an attempt to improve the effectiveness, a cardiotonic such as aminophylline or trans-pi-oxocamphor was added to a solution containing angiotensin II and DDP. A remarkable improvement in therapeutic efficacy was apparent as compared to angiotensin II hypertension chemotherapy. A possible synergism between angiotensin II and the cardiotonic may result in selective delivery of the antitumor drug to the tumor tissue. PMID- 3089977 TI - Effects of sodium chloride and alcohol on experimental esophageal carcinogenesis induced by N-nitrosopiperidine in rats. AB - The effects of sodium chloride and alcohol on esophageal carcinogenesis induced by N-nitrosopiperidine (NNP) were studied in male F-344 rats. Sodium chloride given concomitantly with NNP during the first 8 weeks of the experiment and followed by sodium chloride increased the incidence of esophageal tumors in week 20. Sodium chloride given after NNP during the second 12 weeks of the experiment increased the incidence of esophageal hyperplasia. In the present experiment, no clear effect of alcohol on esophageal carcinogenesis was demonstrated, but alcohol slightly increased the incidence of preneoplastic esophageal tumors in groups given alcohol with and after NNP. These results suggest that sodium chloride may be able to be a potent promoter of the development of esophageal tumors in rats if the conditions of initiation are appropriate. Examination of the incidences of tumors in 9 segments of the esophagus gave no evidence of any portion that was especially susceptible to induction of esophageal tumors. PMID- 3089976 TI - 4-Nitroquinoline 1-oxide-induced pulmonary endocrine cell hyperplasia in Syrian golden hamster. AB - The tumorigenic effects of 4-nitroquinoline 1-oxide (4NQO) on the hamster lung were examined by light and electron microscopy. The hamsters received three subcutaneous injections of 4NQO at a dose of 20 mg/kg body weight at weekly intervals, and were sacrificed at 20, 25, and 30 weeks after the first injection. Hyperplastic endocrine cell lesions were consistently demonstrated in the airway from the lobar bronchi to the bronchiolo-alveolar junctional area by serial sectioning of lung tissue slices of all the treated animals. The hyperplastic lesions contained argyrophilic cells and showed weakly positive immunoreactivity to neuron-specific enolase. Ultrastructurally, some of the cells contained small cored dense granules. PMID- 3089978 TI - Partial purification of C-C36 tumor rejection antigen molecules commonly expressed on syngeneic murine colon tumors, C-C36 and C-C26. AB - The tumor-specific transplantation antigens (TSTAs) of BALB/c mouse colon tumor C C36 were characterized by gel filtration (TKS-gel FPLC), ion exchange chromatography (Mono Q FPLC) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The cell surface antigens were solubilized noncytolytically with 2.5% n-butanol. It was demonstrated that the C-C36 antigens responsible for tumor rejection activity against C-C36 cells had a molecular weight of less than 200,000, and were eluted at 0.4-0.5M NaCl. On the other hand, the cross TSTAs expressed on C-C26 cells were eluted 0.2M NaCl. SDS-PAGE analysis of the partially purified antigens showed that the C-C36 TSTAs had four bands corresponding to molecular weights of 75,000, 68,000, 60,000 and 40,000. In contrast, the cross TSTAs expressed on C-C26 cells gave several major bands corresponding to 110,000, 94,000, 60,000 and 38,000, in addition to faint bands of 75,000 and 68,000. These results indicate that, although the partially purified C-C36 and C-C26 colon tumor antigens inducing rejection of C-C36 tumor challenge in syngeneic hosts showed differences in the ionic strength at which they were eluted, there are three common molecules with molecular weights of 75,000, 68,000 and 60,000, suggesting that these common molecules might be the tumor antigens responsible for the C-C36 colon tumor rejection. PMID- 3089979 TI - Differences of host immune response and of sensitivity to chemotherapeutic agents between two clones of rat fibrosarcoma with different metastatic potential. AB - Differences of host immune response and of chemosensitivity between two clones derived from a methylcholanthrene-induced rat fibrosarcoma and exhibiting different tumorigenic and metastatic potentials were examined. Clone G, which has no metastatic potential, was more sensitive to natural killer cytotoxicity by syngeneic rat spleen cells than clone A, which is highly metastatic. The colony formation of clone G was strongly inhibited by the supernatant obtained from coculture of lymphocytes with either of these two clones. In contrast, the colony formation of clone A was not inhibited by these supernatants. Inhibition of the colony formation of clone G was dependent on the dilution of the supernatant and the incubation time of the lymphocytes and tumor cells used to generate the supernatant. The supernatant from cocultures of lymphocytes and clone G inhibited the colony formation of clone G more strongly than the supernatant from cocultures of lymphocytes and clone A. There was no difference between these two clones in chemosensitivity to seven of the ten chemotherapeutic drugs tested. PMID- 3089980 TI - Reduction of pulmonary metastases of B16 melanoma by human recombinant interleukin 2 and lymphokine-activated killer cells in immunosuppressed C57BL/6 mice receiving anticancer agent. AB - The immunosuppressive effect of a water-soluble nitrosourea derivative, 1-(4 amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), was evaluated in terms of the cytotoxicity of spleen lymphocytes, and the restoring effect of lymphokine-activated killer (LAK) cells and/or human recombinant interleukin-2 (rIL-2) on the cytotoxicities of spleen lymphocytes was examined in ACNU-treated C57BL/6 mice. In addition, we tested whether the administration of LAK cells and/or rIL-2 could reduce the increased numbers of pulmonary metastases in ACNU-treated mice. The maximum effective dose of ACNU suppressed the cytotoxicity of spleen lymphocytes and pretreatment with ACNU enhanced the induction of artificial pulmonary metastases. The administration of LAK cells and/or human rIL-2 restored the cytotoxicity of spleen lymphocytes against YAC-1 and syngeneic B-16 melanoma cells in ACNU-treated mice, and these treatments partially suppressed the increased numbers of artificial pulmonary metastases of B-16 melanoma cells in ACNU-treated mice. These results are extremely important in providing a rationale for the introduction of adoptive immunotherapy using LAK cells and rIL-2 in patients with advanced cancer who are being treated with anticancer agent(s). PMID- 3089981 TI - A bioassay of cisplatin by human tumor clonogenic assay. AB - A new bioassay method for cis-diamminedichloroplatinum (CDDP) using a human tumor clonogenic assay (HTCA) was developed and used to examine the pharmacokinetics of the active form of CDDP in different schedules of administration. The inhibition of colony growth of tumor cells decreased with increase in the % of fetal calf serum in RPMI1640 containing CDDP. By means of this assay, four administration schedules (A, B, C and D) of CDDP were examined. In patients given 40 mg/m2 of CDDP by iv infusion on day 1 twice with a 1 hr interval (schedule A), total platinum was still detectable in plasma at 6 hr by atomic absorption assay. However, the active form of CDDP was no longer detectable at 30 min. In patients treated with 20 mg/m2 of CDDP iv for 20 min daily (schedule B) from day 1 to day 4, the level of total platinum showed a cumulative increase. However, the active form of CDDP was no longer detectable at 30 min, and no cumulative effect was observed. In patients given a high dose (120 mg/m2) of CDDP iv for 30 min on day 1 (schedule C), the peak concentration of active form of CDDP was determined to be 5.0 to 7.0 micrograms/ml, and a level of more than 1.0 micrograms/ml was maintained even after 2 hr in one case. In 2 patients of this group the concentrations of active form of CDDP determined by HTCA were the same as those of ultrafiltrable platinum detected by atomic absorption assay. In 2 of 3 patients given 100 mg of CDDP into the pleural cavity, the active form of CDDP was detected in sera. High-dose CDDP administration was concluded to be preferable to low-dose therapy because of the higher peak concentration and longer residence time of the active form of CDDP in the plasma. Furthermore, it is suggested that a systemic effect of CDDP can be expected even when CDDP is given by intrapleural administration. PMID- 3089982 TI - Cell kinetics and chemosensitivity of human carcinomas serially transplanted into nude mice. AB - Six human carcinoma xenografts serially transplanted into nude mice were used for the study of chemosensitivity and cell kinetics. Three gastric carcinomas (St-4, St-40 and H-111), two colon carcinomas (Co-3 and Co-4) and one breast carcinoma (MX-1) were inoculated into the subcutaneous tissue of BALB/cA nude mice. The maximum tolerable doses of mitomycin C (MMC), adriamycin (ADM), cyclophosphamide (CPA) and 5-fluorouracil (5-FU) were administered when the tumor weights reached 100-300 mg. The response rates of the tumor to these drugs were found to be 3/6 for MMC, 2/6 for 5-FU and 1/6 for ADM and CPA. Percent labeled mitosis curves obtained from 3H-thymidine pulse labeling were analyzed by the method of Quastler and Sherman. It was found that the antitumor effect of MMC was closely correlated with the growth fractions of the tumors (r = -0.98, P less than 0.001), and it appeared that the tumor cells were more sensitive to MMC in the resting stages during the proliferating phase than in the other cell cycle phases. Cell kinetics is considered to be an important factor in determining chemosensitivity, and the system of human tumor xenografts-nude mice seems to be a suitable experimental model for investigating the correlation between cell kinetics and chemosensitivity in vivo. PMID- 3089983 TI - 3-Amino-1-methyl-5H-pyrido[4,3-b]-indole initiates two-stage carcinogenesis in mouse skin but is not a complete carcinogen. AB - In two separate experiments, 2.0 mg of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) was applied to the back of female CD-1 mice twice weekly for 5 weeks followed by application of 2.5 micrograms of 12-O-tetradecanoyl-phorbol-13 acetate (TPA) twice weekly for 47 weeks. Skin squamous cell papillomas and carcinomas developed in 6 of 20 mice (30%) in Experiment 1 and in 3 of 19 mice (16%) in Experiment 2. In contrast, application of 2.0 mg of Trp-P-2 twice weekly for 52 weeks did not produce any skin tumors. These data suggest that Trp-P-2 acts primarily as an initiator, not as a complete carcinogen, for mouse skin. PMID- 3089984 TI - Ha-ras oncogene product in human gastric carcinoma: correlation with invasiveness, metastasis or prognosis. AB - c-Ha-ras oncogene product in human gastric carcinomas was examined by Western blotting and immunohistochemistry using anti-Ha-ras p21 antibody. In Western blotting, high levels of c-Ha-ras p21s were found in gastric carcinomas. Immunohistochemically, c-Ha-ras p21 was detected in 3 (11.1%) of 27 early carcinomas and in 63 (43.8%) of 144 advanced carcinomas. In advanced carcinomas, c-Ha-ras p21-immunoreactivity was correlated with the depth of tumor invasion and was stronger in metastatic tumors than in primary tumors. Patients with c-Ha-ras p21-positive carcinomas had a significantly worse prognosis than those with p21 negative carcinomas. PMID- 3089985 TI - Modulation of phorbol ester receptors in mouse skin by application of quercetin. AB - The topical application of quercetin, an anti-tumor promoter, to mouse skin reduced the number of phorbol ester receptors, although quercetin did not inhibit specific 3H-12-O-tetradecanoylphorbol-13-acetate binding to a mouse skin particulate fraction. Quercetin, morin, kaempferol and luteolin inhibited activation of protein kinase C by teleocidin, and caused half-maximal activation at 25 microM. (+)-Catechin, which has been reported not to inhibit tumor promoting activity, did not have any effect on these reactions. The modulation of phorbol ester receptors and inhibition of activation of protein kinase C are considered to be involved in the anti-tumor-promoting effect of quercetin in mouse skin. Diet containing 4% or 1% quercetin did not influence the action of teleocidin on mouse skin in a two-stage carcinogenesis experiment. PMID- 3089986 TI - Increased expression of the c-myc gene without gene amplification in human lung cancer and colon cancer cell lines. AB - High levels of c-myc mRNA were observed in two human tumor cell lines, a giant cell carcinoma of the lung (C-Lu99) and a colon cancer (C1). The increased expression of c-myc in these cell lines, which was comparable with those in cell lines in which the c-myc gene is amplified, was not due to gene amplification. Run-on transcription revealed that the transcriptional rate of the c-myc gene was greatly increased in these cell lines. PMID- 3089987 TI - Enhanced expression of a 37,000-dalton protein in human lung cancers. AB - When proteins in the tissue extracts of lung cancers were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE), a 37,000-dalton protein (37K) was detected as a prominent form in all cases thus far examined. This protein was barely detectable or its amount was very small in the normal lung tissue extracts. Two-dimensional PAGE of lung tumor extracts showed 37K as a major spot with an isoelectric point of 7.6. An antibody against 37K was raised in a rabbit by injecting purified 37K. Immunoblot analysis of normal lung and lung tumor tissues revealed that the affinity-purified anti-37K antibody specifically recognized 37K and that the intensities of immunostaining corresponded to those of Coomassie brilliant blue staining. PMID- 3089988 TI - Similarity between glyceraldehyde-3-phosphate dehydrogenase and a 37,000-dalton protein which is abundantly expressed in human lung cancers. AB - Human lung cancers of all histological types contain a protein of 37,000 daltons (37K) as an abundant component. Partial sequence analysis of purified 37K revealed a strong homology with glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12). Tryptic peptide mapping analysis showed that the pattern of 37K was very similar to those of GAPDHs both purified from lung tumor and obtained commercially. An antibody raised against 37K in a rabbit also reacted with authentic GAPDH. These results suggest a possible involvement of GAPDH itself or a GAPDH-related protein in lung tumorigenesis. PMID- 3089989 TI - High level of beta-type transforming growth factor activity in human urine obtained from cancer patients. AB - Activity of transforming growth factor (TGF) in urine was examined by the use of cloned BALB/3T3 A31-1-1 indicator cells. When urine was extracted by an acid ethanol method, fractionated on a Bio-Gel P-100 column, and analyzed for TGF activity, samples from healthy persons showed no activity, but 80% of the samples from advanced cancer patients had the activity. Activity observed in tumor bearing patients was eliminated after therapy. Further analysis was carried out in a much simpler way by the fractionation of urine samples after only dialysis and lyophilization. An extensive survey of TGF activity in urine using BALB/3T3 indicator cells revealed weak or intermediate (19%) activity in healthy persons and high (56%) or intermediate (31%) activity in advanced cancer patients. When urine samples were analyzed and compared using both BALB/3T3 cells and NRK 49F cells, the BALB/3T3 cells were shown to form colonies in response to beta-type TGF but not to alpha-type TGF. The present results are the first demonstration of an elevated level of beta-type TGF in urine from cancer patients. PMID- 3089990 TI - Accelerating effect of nude gene heterozygosity on spontaneous AKR thymic lymphomagenesis. AB - The effect of nude gene heterozygosity on spontaneous AKR thymic lymphomagenesis was studied by comparing female littermates of AKR/Ms-nu/+ and +/+. As previously reported in nude gene heterozygotes with genetic background other than AKR, AKR/Ms-nu/+ mice had a significantly smaller thymus than the +/+ littermates. Overall incidences of thymic lymphomas were comparable in the two genotypes, but the mean latent period for lymphoma development was significantly shorter in the nu/+ mice (266.3 +/- 11.6 days) than in the +/+ mice (319.3 +/- 7.9 days). Both genotypes of mice expressed a high level of XC+-ecotropic murine leukemia virus. Expression of xenotropic virus was more variable, but there was no consistent difference in onset of virus expression or in virus titer that could explain accelerated lymphomagenesis in the nude gene heterozygotes. PMID- 3089991 TI - Role of the thymus in propylnitrosourea-induced thymic lymphomagenesis in F344 rats. AB - The role of the thymus in propylnitrosourea (PNU)-induced thymic lymphomagenesis was studied in F344 rats with genetically determined high susceptibility. The thymus was absolutely required for thymic lymphomagenesis, since thymectomy prior to or after PNU treatment abolished lymphomagenesis, whereas grafting of a normal neonatal thymus before PNU treatment restored it. Exposure to PNU for 42 days resulted in the appearance of potentially lymphomatous cells first in the thymus, and overt T-lymphomas subsequently appeared. Such cells seemed to be thymus dependent, since intrathymic transfer of the thymus cells from 42-day PNU-treated rats induced T-lymphomas much more efficiently than intravenous transfer. Further, grafting of the thymus from 42-day PNU-treated rats into thymectomized rats resulted in T-lymphomas of donor origin without additional PNU treatment. Cells from the spleen or bone marrow from the same donors did not give rise to T lymphomas irrespective of the route of cell transfer and sublethal irradiation of the recipients. Morphologically atypical cell foci were detected first on the 28th day in the thymus and were most pronounced during the 35th-42nd days. Therefore, the thymus is the essential organ in which the early events of PNU induced rat T-lymphomagenesis take place. PMID- 3089992 TI - Cancer mortality among patients undergoing cholecystectomy for benign biliary diseases. AB - Potential risks of gastrointestinal cancers after cholecystectomy were examined among 1238 patients who had had their gallbladders extirpated for benign biliary diseases from 1951 to 1970. The observed deaths between 1953 and 1984 were compared with the expected values which were calculated from death rates in Japan. No appreciable excess mortality was found for stomach cancer, colorectal cancer or pancreas cancer in relation to cholecystectomy. Observed and expected deaths during the whole observation period were 29 vs. 31.58 for stomach cancer, 8 vs. 6.50 for colorectal cancer overall, 5 vs. 3.19 for colon cancer and 3 vs. 3.51 for pancreas cancer. The corresponding figures in the 10 years or more after cholecystectomy were 14 vs. 19.06 for stomach cancer, 5 vs. 4.66 for colorectal cancer and 3 vs. 2.38 for colon cancer. A notably increased mortality from liver cancer was observed, but it was considered to be related not to cholecystectomy itself but to blood transfusion. PMID- 3089993 TI - Human IgM monoclonal anti-GD2 antibody: reactivity to a human melanoma xenograft. AB - The cell membranes of human melanoma express a tumor-associated ganglioside, GD2. We previously established a human melanoma cell line, M14-A, that metastasizes to the lung, liver, skin, lymph nodes, and abdominal organs of nude mice in addition to forming ascites and pleural effusions. We also reported the successful in vitro production of human IgM monoclonal antibody to GD2. In the present study, we evaluated the GD2 expression of human melanoma cells at the primary and metastatic sites and their reactivity to human monoclonal anti-GD2 antibody in vivo. GD2 was expressed strongly on the melanoma cells from both primary and metastatic sites, except for cells from pleural effusions and ascites. When M14-A bearing nude mice received systemic injections of the human monoclonal antibody, the anti-GD2 titer in the sera was reduced markedly at 2 hours, whereas the reduction was minimal in sera from tumor-free mice and mice bearing GD2-negative human M24 cells. The immune adherence test confirmed that antibody was fixed on cells of primary subcutaneous M14-A tumors and on their metastases to liver, lung, abdominal organs and skin. These results suggest that this large molecule protein can penetrate the blood-tumor barrier and bind immunologically to antigen positive melanoma cells in vivo. PMID- 3089994 TI - Syngeneic monoclonal anti-melanoma antibody that inhibits experimental lung metastasis of B16 melanoma. AB - An objective method to evaluate experimental lung metastasis of murine melanoma has been established by sandwich radioimmunoassay using monoclonal anti-melanoma antibody (M2590). The assay system quantitatively detected melanoma antigens metastasized in the lung. The data obtained by radioimmunoassay were consistent with those obtained by the usual colony-counting method. By the use of these detection systems for lung metastasis, we found that only one particular syngeneic monoclonal antibody (M562) recognizing a proteinaceous determinant on melanoma antigen significantly inhibited experimental lung metastasis of melanoma cells (1/7-1/10 of controls), whereas other syngeneic monoclonal antibodies with the same specificity and the same immunoglobulin class or control antibody did not. It is therefore strongly suggested that the molecule recognized by M562 antibody plays an important role in lung metastasis of melanoma cells. PMID- 3089995 TI - Antitumor effect of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha,alpha trehalose (SS554), in mice. AB - The antitumor effect on Meth-A fibrosarcoma in BALB/c mice of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha,alpha-trehalose (designated as SS554), was examined. Only intratumoral injection had a curative effect; subcutaneous, per oral, or intravenous routes had no such effect. The co-presence of an oily vehicle has been shown to be necessary for antitumor activity of a natural cord factor. When SS554 was examined in suspensions of sesame oil, squalane, squalene or sesame oil and water emulsion, a 60% cure rate was achieved. However, no such effect was obtained with a suspension in Tween-PBS or a solution. It should also be noted that sequential but independent administrations of SS554 and oil were found to be as effective as the simultaneous administration of oil and SS554 in emulsion form. In the case of the emulsion, the amount of sesame oil necessary was over 10%, or 0.01 ml in absolute terms. Cures were obtained in a dose dependent manner by injection of SS554 in amounts in excess of 1 mg. The effect of the time of administration was also examined; the best result was obtained when intratumoral injection was done on day 3 after tumor implantation. Mice cured by SS554 exhibited growth inhibition and rejection of rechallenged Meth-A cells. However, this immunity was specific; it did not extend to a rechallenge with RLmale-1 leukemia cells. PMID- 3089996 TI - Revised structure of mycosubtilin, a peptidolipid antibiotic from Bacillus subtilis. AB - The structure of mycosubtilin, a peptidolipid antibiotic from Bacillus subtilis, was revised by FAB mass spectrometry, 2D NMR spectrometry and also by Edman degradation of the peptide resulting from the N-bromosuccinimide reaction. Four homologous beta-amino acid components were identified by capillary gas chromatography. The cyclopeptide mycosubtilin consists of seven alpha-amino acids in an LDDLLDL sequence closed by a beta-amino acid linkage similar to that found in other antibiotics of the iturin group. PMID- 3089997 TI - Plipastatins: new inhibitors of phospholipase A2, produced by Bacillus cereus BMG302-fF67. I. Taxonomy, production, isolation and preliminary characterization. AB - Plipastatins have been isolated as part of a program designed to find inhibitors of porcine pancreatic phospholipase A2. They were purified from fermentation broth of Bacillus cereus BMG302-fF67 and finally separated into four fractions by reverse phase HPLC. The respective fractions were designated as plipastatins A1, A2, B1 and B2. Plipastatins also inhibited phospholipases C and D. PMID- 3089999 TI - Plipastatins: new inhibitors of phospholipase A2, produced by Bacillus cereus BMG302-fF67. III. Structural elucidation of plipastatins. AB - Plipastatins are new inhibitors of phospholipase A2 produced by Bacillus cereus BMG302-fF67. Structures of the plipastatins have been determined by UV, mass and NMR spectrometries and chemical degradation. The carboxyl group of the C-terminal L-isoleucine of plipastatinic acid has been shown to form a lactone linkage with the hydroxyl group of L-tyrosine. The total structure of plipastatins has thus been established. PMID- 3089998 TI - Plipastatins: new inhibitors of phospholipase A2, produced by Bacillus cereus BMG302-fF67. II. Structure of fatty acid residue and amino acid sequence. AB - Plipastatins, new inhibitors of phospholipase A2, were produced by a strain classified as Bacillus cereus BMG302-fF67. The plipastatins are a family of acylated decapeptides which differ from each other by amino acid composition and the nature of the fatty acid side chain. The fatty acids have been shown to be 3(R)-hydroxyhexadecanoic acid (n-C16h3) and 14(S)-methyl-3(R)-hydroxyhexadecanoic acid (a-C16h3) by mass, NMR and optical rotation. Amino acid sequence analysis by secondary ion mass spectrometry and additional physico-chemical evidence indicate that the structures of plipastatinic acids, the lactone-opened peptides are as follows: beta-Hydroxy fatty acid----L-Glu----D-Orn----L-Tyr----D-allo-Thr----L Glu----D-Ala(Val)---- L-Pro----L-Gln----D-Tyr----L-Ile X OH. PMID- 3090000 TI - In vitro and in vivo effects of differanisole A on some tumor cells. PMID- 3090001 TI - Overview of mechanical damage to the inner ear: noise as a tool to probe cochlear function. AB - The majority of experiments causing mechanical damage to the cochlea involve the use of sound pressure waves to cause overstimulation. This presentation is an overview of the research during the past years on the structural damage produced by noise. The effect of noise on the cochlea depends on the type of noise exposure-impulse or continuous. Experiments have been conducted to determine the effect of increasing intensity, the effect of increasing duration, and the effect of equal energy presented over varying periods of time. The initial mechanism of damage, the progression of damage over time, and the ability of hair cells to recover are discussed. Noise has been used as a tool to probe cochlear function by selectively damaging regions along the length of the sensory epithelium and by selectively damaging one of the two types of hair cells. Results obtained from these types of experiments have given us information on cochlear mechanics, as well as of stereocilia micromechanics and transduction. Information on susceptibility of hair cells to noise confirms previous results, suggesting the presence of structural and metabolic gradients both longitudinally and radially within the sensory epithelium. Moreover, noise lesions have been used to map the afferent innervation pattern to the cochlear nucleus, and noise studies show correlation of hair cell damage with efferent innervation pattern. PMID- 3090002 TI - Threonine requirement of pigs weighing 5 to 15 kg. AB - Weanling crossbred pigs (avg initial wt 6.4 kg) were fed diets containing six levels of threonine to determine the threonine requirement of young pigs fed diets somewhat similar to those used in commercial swine production. The diets (16% crude protein) were composed primarily of grain sorghum, oat groats and soybean meal supplemented with minerals, vitamins, lysine, tryptophan, methionine and isoleucine, and were calculated to be adequate in all nutrients except threonine and crude protein. Threonine levels were .53, .57, .62, .68, .75 and .83% of the diet. There were two trials, each with 96 pigs. The pigs were fed the experimental diets for 28 d. The addition of threonine increased weight gain (P less than .02) and feed efficiency (P less than .001), with most of the response occurring between .53 and .68% threonine. There was little further response when threonine was increased above .68%. Plasma threonine concentrations increased as dietary threonine increased, with a sharp rise when dietary threonine exceeded .68%. Concentrations of most other essential amino acids in the plasma declined in response to increasing dietary threonine, and reached minimum values at either .68 or .75% threonine. Plasma urea concentrations decreased as threonine was increased in the diet, reaching a plateau at .68% dietary threonine. The data indicate the young pigs weaned at 3 to 4 wk of age require approximately .70% threonine. PMID- 3090003 TI - Clearance rate of luteinizing hormone and follicle stimulating hormone from peripheral circulation in the pig. AB - Passive immunization of chronically ovariectomized gilts against gonadotropin releasing hormone (GnRH) resulted in an abrupt cessation of pulsatile secretion of luteinizing hormone (LH) accompanied by clearance from serum with a mean half life of 30.9 +/- 2.3 (mean +/- SE) and 918 +/- 200 min for the first and second compartment, respectively. Serum follicle stimulating hormone (FSH) was unaffected immediately by passive immunization against GnRH and declined slowly with a half-life of 4.9 +/- .7 d. After LH and FSH had declined to basal levels in passively immunized gilts, injection of a bolus of LH and FSH resulted in peak values within 5 min and depletion curves with half-lives for the first compartment of 28.0 +/- 1.3 and 36.4 +/- 2.6 min and for the second compartment of 679 +/- 98 and 1,230 +/- 54 min, for LH and FSH respectively. These results show that the half-life of LH is similar following immunoneutralization of GnRH or administration of a bolus of LH in immunized gilts and a difference in clearance rates of LH and FSH after initial passive immunization. These results suggest that secretion of FSH in the ovariectomized gilt is controlled by factors in addition to hypothalamic GnRH. PMID- 3090004 TI - Androgen and estradiol effects on gonadotropin secretion and response to GnRH in ovariectomized pony mares. AB - In Exp. 1, 16 long-term ovariectomized pony mares were used to determine the effects of treatment with estradiol benzoate (EB) and dihydrotestosterone (DHT) benzoate alone, and in combination, on secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in daily blood samples and after three consecutive injections of gonadotropin releasing hormone (GnRH). Administration of EB alone, or in combination with DHT, every other day for 11 d reduced (P less than .05) concentrations of FSH and increased (P less than .05) concentrations of LH in daily blood samples, and increased (P less than .05) the secretion of both gonadotropins after administration of GnRH. Treatment with DHT alone had no effect (P greater than .10) on LH or FSH concentrations in daily blood samples and no effect on the LH response to exogenous GnRH. There was no interaction (P greater than .10) between DHT and EB treatment for any hormonal characteristic. In Exp. 2, the control mares and mares treated with DHT in Exp. 1 were equally allotted to treatment with vehicle or testosterone propionate (TP) every other day for six injections, and then GnRH was administered as in Exp. 1. Treatment with TP had no effect (P greater than .10) on LH or FSH concentrations in daily blood samples but increased (P less than .05) the FSH response to exogenous GnRH, confirming our findings in previous experiments. It is concluded that the TP induced stimulation of FSH secretion after exogenous GnRH in ovariectomized mares may involve estrogens produced from aromatization of the injected androgen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090005 TI - Effect of dry, high-moisture and reconstituted normal and high-lysine corn diets and particle size on energy and nitrogen metabolism in growing swine. AB - Two metabolism studies were conducted with 24 (Exp. 1) and 36 (Exp. 2) crossbred barrows (initial weight 35 kg) to determine the effect of corn type--normal corn (NC) and high-lysine corn (HLC)--and storage method--dry (D), high-moisture (HM) and reconstituted (RC)--on energy and N digestibility. Diets fed in Exp. 1 were: 1, NC-soybean meal formulated at .78% lysine (dry matter basis); 2, HLC-soybean meal containing the same amount of corn as diet 1 (.87% lysine); 3, HLC-soybean meal with the same lysine level as diet 1. In Exp. 1, dry matter, energy and N digestibilities were not different between corn types or lysine levels (P greater than .16). These results indicate that energy and N digestibility of HLC in typical diets for growing swine are similar to those for NC diets when both are balanced on a lysine basis. Also, replacing NC with HLC on an equal-weight basis did not affect energy and N digestibility. In Exp. 2 six diets balanced on an isonitrogenous and dry-matter basis were tested. Normal corn and HLC diets, which had been stored by three different methods (D, HM and RC) were arranged in a 2 X 3 factorial plan. There were no differences between corn types in dry matter, energy and N digestibilities. The HM and RC treatments had larger particle sizes than the dry corn diets. For diets balanced on an isonitrogenous basis, dry corn storage improved energy digestibility (P less than .10). Reconstitution appeared to improve energy balance and N digestibility of HLC, while HM storage improved energy balance and N digestibility of NC. PMID- 3090006 TI - Age, dose of FSH and other factors affecting superovulation in Holstein cows. AB - Effects of age of donor and other factors on superovulation and production of transferable embryos were investigated. Data were obtained on 987 recoveries of embryos performed between November 1980 and June 1984 by Select Embryos, Inc. The 339 Holstein donors ranged in age from 1.8 to 17.8 yr. The effects of age of donor and dose of follicle stimulating hormone (FSH) were examined using regression analysis. For on-farm recoveries, numbers of embryos, rates of fertilization, quality scores of all embryos and numbers of transferable embryos decreased (P less than .01, P less than .001, P less than .05, P less than .01, respectively) with increasing age of donor. For in-clinic recoveries, numbers of embryos plus ova recovered were affected by age of donor, dose of FSH and the interaction of the two (P less than .05). Among older donors, increasing doses of FSH were associated with an increase in the number of ova plus embryos recovered. However, among younger donors, increasing doses of FSH had a negative effect. Numbers of embryos, rates of fertilization and numbers of transferable embryos decreased (P less than .05) with advancing age and increased (P less than .05) with increasing doses of FSH. Greater numbers of ova plus embryos were recovered when treatment with FSH was begun on d 10 or 11 as compared with d 7, 8, 9, 12, 13 or 14 (P less than .001). It was concluded that an increase in age of donor had a negative influence on the success of superovulation and the production of transferable embryos, and that the response to FSH was affected by age of donor. PMID- 3090007 TI - In-vitro emergence of beta-lactam-resistant variants of Pseudomonas aeruginosa. AB - The frequency with which resistant variants could be found in Pseudomonas aeruginosa ATCC 27853 during growth in media with and without antibiotics was determined for ticarcillin, piperacillin, cefotaxime, latamoxef, cefoperazone, ceftriaxone, ceftazidime, aztreonam and imipenem. The resistance frequency was highest for ceftriaxone, cefotaxime, cefoperazone and piperacillin (up to 2 X 10( 4)) and lowest for ticarcillin, latamoxef, ceftazidime, aztreonam and imipenem (less than 10(-8)). The resistant variants showed cross-resistance to all of the beta-lactam antibiotics tested with the exception of imipenem. The MIC profiles of all variants were similar regardless of which antibiotic the cultures had been exposed to previously. Although all resistant variants produced and excreted cephalosporinases, increased resistance was demonstrated to both cephalosporinase susceptible and cephalosporinase-stable beta-lactam antibiotics. PMID- 3090008 TI - Resistance to cefsulodin and gentamicin in Pseudomonas aeruginosa strains in five areas of Japan between 1980 and 1983. AB - The activities of cefsulodin and gentamicin against Pseudomonas aeruginosa isolated from clinical specimens from five hospitals in different geographical areas of Japan, from 1980 to 1983, were compared in vitro. The incidence of resistant strains was higher for gentamicin. In 1982 the sensitivity to both drugs decreased from 1980 and 1981 levels, largely because of the isolation of numbers of cefsulodin-gentamicin cross-resistant bacteria from three of the five hospitals. In 1983, the incidence of resistant strains was similar to that in 1982. This linked cefsulodin-gentamicin resistance may have been selected by the use of the cephalosporins, cefmenoxime, cefoperazone, cefotaxime, ceftizoxime and latamoxef, which had been prescribed extensively in the hospitals where cross resistance was encountered. Although cefsulodin-resistant strains of P. aeruginosa have increased since 1982, the in-vitro activity of cefsulodin in 1983 remained greater than that of these third-generation cephalosporins. PMID- 3090009 TI - Comparison of the effect of phenoxymethylpenicillin, cloxacillin, and flucloxacillin on Staphylococcus aureus phagocytosed by human monocytes. AB - The antibacterial effect of phenoxymethylpenicillin, cloxacillin, and flucloxacillin on pre-opsonized Staphylococcus aureus ingested by human monocytes and on preopsonized S. aureus in suspension was compared. The antibiotics were 1.7-3 times more effective against intracellular S. aureus than against S. aureus in suspension. No influence of acid stability or lipid solubility of the drugs on the antibacterial effect against intracellular S. aureus was demonstrated. PMID- 3090010 TI - Influence of ofloxacin, norfloxacin, nalidixic acid, pyromidic acid and pipemidic acid on human gamma-interferon production and blastogenesis. AB - Several new quinolone derivatives were investigated for their influence on human lymphocyte blastogenesis and gamma-interferon production following concanavalin A stimulation. All the antimicrobials induced inhibition of lymphocyte DNA synthesis. The gamma-interferon measurements showed that nalidixic acid and norfloxacin have a negative influence on lymphokine production and release. PMID- 3090011 TI - Comparison of two noninvasive techniques for estimating cardiac output during exercise. AB - This study presents the comparison of two different noninvasive techniques for the estimation of cardiac output (Q). The two techniques used were transthoracic impedance plethysmography (Z) and the indirect Fick CO2 rebreathing (RB) method. Paired estimates of Q were made on 60 different male subjects at rest and during graded increments of work on a cycle ergometer. The mean resting Q as measured by the Z technique (COZ) was 7.46 +/- 0.35 and 5.96 +/- 0.43 l/min using the RB (CORB) technique. At 200 W the mean COZ was 18.67 +/- 0.72 l/min and the CORB was 23.73 +/- 0.84 l/min. Both the techniques were linearly correlated (R) with O2 consumption; i.e., RZ = 0.752, RRB = 0.855. The difference between these two R values is statistically significant (P less than 0.001). A linear relationship was found between the Z and RB techniques at all work loads (R = 0.75). This study suggests that both techniques are equally as reliable over a large range of work loads, with the Z technique being the simplest and most efficient to implement. It was also found that lung volume had no effect on the calculated COZ. PMID- 3090012 TI - Pulmonary gas exchange in humans exercising at sea level and simulated altitude. AB - In a previous study of normal subjects exercising at sea level and simulated altitude, ventilation-perfusion (VA/Q) inequality and alveolar-end-capillary O2 diffusion limitation (DIFF) were found to increase on exercise at altitude, but at sea level the changes did not reach statistical significance. This paper reports additional measurements of VA/Q inequality and DIFF (at sea level and altitude) and also of pulmonary arterial pressure. This was to examine the hypothesis that VA/Q inequality is related to increased pulmonary arterial pressure. In a hypobaric chamber, eight normal subjects were exposed to barometric pressures of 752, 523, and 429 Torr (sea level, 10,000 ft, and 15,000 ft) in random order. At each altitude, inert and respiratory gas exchange and hemodynamic variables were studied at rest and during several levels of steady state bicycle exercise. Multiple inert gas data from the previous and current studies were combined (after demonstrating no statistical difference between them) and showed increasing VA/Q inequality with sea level exercise (P = 0.02). Breathing 100% O2 did not reverse this increase. When O2 consumption exceeded about 2.7 1/min, evidence for DIFF at sea level was present (P = 0.01). VA/Q inequality and DIFF increased with exercise at altitude as found previously and was reversed by 100% O2 breathing. Indexes of VA/Q dispersion correlated well with mean pulmonary arterial pressure and also with minute ventilation. This study confirms the development of both VA/Q mismatch and DIFF in normal subjects during heavy exercise at sea level. However, the mechanism of increased VA/Q mismatch on exercise remains unclear due to the correlation with both ventilatory and circulatory variables and will require further study. PMID- 3090014 TI - Effect of hypocapnia on ventral medullary blood flow and pH during hypoxia in cats. AB - Ventral medullary blood flow was measured in 33 chloralose-urethan anesthetized cats during 60 min of isocapnia-hypoxia, mild hypocapnia-hypoxia, or severe hypocapnia-hypoxia. In an additional group of six animals we measured ventral medullary extracellular fluid (ECF) pH during mild hypocapnia-hypoxia. The increase in blood flow during hypoxia was reduced by mild hypocapnia and eliminated by severe hypocapnia. With the exception of an initial decrease in ECF [H+], which occurred during the first 10 min of mild hypocapnia-hypoxia, ECF [H+] increased progressively throughout the exposure and recovery periods and was significantly elevated from the control value by the first 10 min of the recovery period. The results suggest that hypocapnia affects the hypoxic cerebrovascular response of the ventral medulla and that this phenomenon could affect the regulation of ventral medullary ECF [H+]. PMID- 3090013 TI - Dimethylthiourea decreases acute lung edema in phorbol myristate acetate-treated rabbits. AB - Treatment with dimethylthiourea (DMTU), a potent O2 metabolite scavenger, prevented neutrophil-mediated acute edema in lungs of rabbits given phorbol myristate acetate (PMA) and in isolated rabbit lungs perfused with neutrophils and PMA. DMTU-treated rabbits given PMA did not increase their lung weight-to total body weight ratios (5.0 +/- 0.3) or lung lavage albumin concentrations (14 +/- 4.6 mg/dl) in comparison to untreated rabbits given PMA (6.6 +/- 0.5 and 60 +/- 10 mg/dl, respectively). Similarly, DMTU-treated isolated rabbit lungs perfused with neutrophils and PMA did not gain weight (0 g) or increase their lavage albumin concentrations (82 +/- 17 mg/dl) in comparison to untreated lungs perfused with neutrophils and PMA (71 +/- 3.1 g and 1,299 +/- 47 mg/dl, respectively). DMTU did not appear to decrease edema by preventing increases in pulmonary arterial pressures (PAP). First, treatment with DMTU did not decrease initial PAP increases in rabbits given PMA. Second, even though addition of DMTU attenuated PAP increases in isolated lungs perfused with neutrophils and PMA, DMTU-treated isolated lungs did not develop acute edema when subjected to mechanical increases in venous outflow pressures. The mechanism by which DMTU decreases lung edema is unclear but may involve scavenging of toxic O2 metabolites, since DMTU also decreased hydrogen peroxide (H2O2) and hydroxyl radical (OH) concentrations in in vitro mixtures containing neutrophils and PMA. PMID- 3090015 TI - A sporadic case of epidemic (louse-borne) typhus. PMID- 3090016 TI - Penicillin-binding site on the Escherichia coli cell envelope. AB - The binding of 35S-labeled penicillin to distinct penicillin-binding proteins (PBPs) of the "cell envelope" obtained from the sonication of Escherichia coli was studied at different pHs ranging from 4 to 11. At low pH, PBPs 1b, 1c, 2, and 3 demonstrated the greatest amount of binding. At high pH, these PBPs bound the least amount of penicillin. PBPs 1a and 5/6 exhibited the greatest amount of binding at pH 10 and the least amount at pH 4. With the exception of PBP 5/6, the effect of pH on the binding of penicillin was direct. Experiments distinguishing the effect of pH on penicillin binding by PBP 5/6 from its effect on beta lactamase activity indicated that although substantial binding occurred at the lowest pH, the amount of binding increased with pH, reaching a maximum at pH 10. Based on earlier studies, it is proposed that the binding at high pH involves the formation of a covalent bond between the C-7 of penicillin and free epsilon amino groups of the PBPs. At pHs ranging from 4 to 8, position 1 of penicillin, occupied by sulfur, is considered to be the site that establishes a covalent bond with the sulfhydryl groups of PBP 5. The use of specific blockers of free epsilon amino groups or sulfhydryl groups indicated that wherever the presence of each had little or no effect on the binding of penicillin by PBP 5, the presence of both completely prevented binding. The specific blocker of the hydroxyl group of serine did not affect the binding of penicillin. These observations suggest that a molecule of penicillin forms simultaneous bonds between its S at position 1 and sulfhydryl groups of PBP 5 and between its C-7 and free epsilon amino groups of PBP 5. PMID- 3090017 TI - N5-(1-carboxyethyl)-ornithine, a new amino acid from the intracellular pool of Streptococcus lactis. AB - Intracellular concentrations of amino acids were determined in cells of Streptococcus lactis 133 during growth in complex, spent, and chemically defined media. Glutamic and aspartic acids represented the major constituents of the amino acid pool. However, organisms grown in spent medium or in defined medium supplemented with ornithine also contained unusually high levels of two additional amino acids. One of these amino acids was ornithine. The second compound exhibited properties of a neutral amino acid by coelution with valine from the amino acid analyzer. The compound did not, however, comigrate with valine or any other standard amino acid by two-dimensional thin-layer chromatography. The unknown amino acid was purified by paper and thin-layer chromatography, and its molecular structure was determined by 1H and 13C nuclear magnetic resonance spectroscopy. This new amino acid was shown to be N5-(1 carboxyethyl)-ornithine. The 14C-labeled compound was formed by cells of S. lactis 133 during growth in spent medium or defined medium containing [14C]ornithine. Formation of the derivative by resting cells required ornithine and the presence of a metabolizable sugar. N5-(1-Carboxyethyl)-ornithine was synthesized chemically from both poly-S-ornithine and (2S)-N2-carbobenzyloxy ornithine as a 1:1 mixture of two diastereomers. The physical and chemical properties of the amino acid purified from S. lactis 133 were identical to those of one of the synthetic diastereomers. The bis-N-trifluoroacetyl-di-n-butyl esters of the natural and synthetic compounds generated identical gas chromatography-mass spectrometry spectra. A mechanism is suggested for the in vivo synthesis of N5-(1-carboxyethyl)-ornithine, and the possible functions of this new amino acid are discussed. PMID- 3090019 TI - Expression of cellulase genes in Rhodobacter capsulatus by use of plasmid expression vectors. AB - Broad-host-range plasmid vectors were constructed for expression of heterologous genes in the photosynthetic bacterium Rhodobacter capsulatus. These plasmids utilize an RK2-derived replicon for maintenance and conjugative transfer and the R. capsulatus rxcA promoter to obtain transcription of genes within appropriately positioned DNA fragments. The expression vectors were used to obtain synthesis of endoglucanase and exoglucanase in R. capsulatus from cellulase genes present on exogenously derived DNA fragments. The cellulase genes were expressed either by use of their native translation initiation signals or by in-frame fusion with the rxcA B870 beta gene translation initiation signals to form a hybrid protein. The level of cellulase gene expression was found to be modulated in response to the extent of aeration of plasmid host cultures. PMID- 3090018 TI - Respiratory systems of the Bacillus cereus mother cell and forespore. AB - The respiratory systems of the mother cells and forespores of Bacillus cereus were compared throughout the maturation stages (III to VI) of sporulation. The results indicated that both cell compartments contain the same assortment of oxidoreductases and cytochromes. However membrane fractions from young forespores were clearly distinct from those of the mother cell, i.e., lower content of cytochrome aa3, lower cytochrome c oxidase activity, higher concentration of cytochrome o, and a lower sensitivity of the respiration to the inhibiting effect of cyanide. This suggests that the cyanide-resistant pathway contributes more importantly to forespore respiratory activity than to activity in the mother cell compartment. During the maturation stages, the forespore NADH oxidase activity declined faster than in the mother cells. Other activities studied decreased steadily in both cell compartments. These findings together with the analysis of the kinetics of NADH-dependent reduction of cytochromes in the mature spore membranes indicated an impairment of electron flow between NADH dehydrogenase and cytochrome b. This impairment could be overcome by the addition of menadione. PMID- 3090020 TI - Utilization of purines or pyrimidines as the sole nitrogen source by Methanococcus vannielii. AB - Studies of biosynthetic pathways with purines as substrates showed that Methanococcus vannielii was capable of degrading xanthine to an extent that several of the carbon atoms were converted to CO2. Experiments to determine whether this catabolic activity could satisfy the entire nitrogen requirement for growth of M. vannielii showed that urate, guanine, xanthine, or hypoxanthine, but not adenine, could serve as the sole nitrogen source. The pyrimidines uracil and thymine, but not cytosine, were also degraded to serve as a source of nitrogen. Although urate was extensively degraded, it did not replace formate as the sole carbon source for growth of M. vannielii under the conditions imposed. PMID- 3090021 TI - Construction of isogenic gonococcal strains varying in the presence of a 4.2 kilobase cryptic plasmid. AB - A 4.2-kilobase (kb) cryptic plasmid is present in 96% of isolates of Neisseria gonorrhoeae. An inability to construct isogenic derivatives which vary in the presence of the 4.2-kb plasmid has prevented the study of its function. We report a method to deliver an intact 4.2-kb plasmid into plasmidless gonococcal strains. The method involved transformation with novel 15.7-kb hybrid penicillinase producing (Pcr) plasmids, which were cointegrates containing two copies of the 4.2-kb plasmid arranged in tandem direct repeat plus one copy of the 7.2-kb Pcr plasmid pFA3. When the 15.7-kb hybrid Pcr plasmids were introduced into a gonococcal recipient lacking evident plasmids, they dissociated at a relatively high frequency into plasmids identical to their parents: the 4.2-kb cryptic plasmid and pFA10 (a stable 11.5-kb plasmid containing one copy of each of the 7.2-kb Pcr plasmid pFA3 and the 4.2-kb cryptic plasmid pFA1). Curing strains of their Pcr plasmids resulted in isogenic strains which varied only in the presence of the 4.2-kb plasmid. The presence of the autonomously replicating 4.2-kb plasmid did not affect a number of tested phenotypes, including auxotype, antibiotic sensitivity, and frequencies of variation of outer membrane protein II. The interpretation of the functional significance of the 4.2-kb plasmid was complicated, however, by the additional finding that each of three tested plasmid free strains contained a chromosomal fragment of about 1.6 kb that hybridized under moderate stringency with a 1.65-kb HinfI fragment of the 4.2-kb plasmid. PMID- 3090022 TI - nprR1 and nprR2 regulatory regions for neutral protease expression in Bacillus subtilis. AB - The gene coding for the Bacillus subtilis extracellular neutral protease was isolated from strain BGSC 1A341, an overproducer carrying the nprR2 region, and from strain 168, a normal producer with the nprR1 sequence. The sequence of about 600 nucleotides upstream from the start codon of the protease gene was determined for both strains. The two regions are highly homologous except for a stretch of 66 base pairs close to the promoter region, which is absent in the BGSC 1A341 gene. Northern blot analysis of the in vivo RNAs indicated that the different levels of enzyme secreted by the two strains were due to different amounts of transcripts that accumulated in the cells. Furthermore, at the end of exponential growth, the amount of transcript increased dramatically in the overproducer strain but remained approximately constant in the normal producer strain. The start point(s) for transcription, however, as determined by S1 nuclease mapping of the in vivo transcripts, appeared to be the same for both genes. PMID- 3090023 TI - Genetic analysis of Myxococcus xanthus and isolation of gene replacements after transduction under conditions of limited homology. AB - Genetic analysis of Myxococcus xanthus is greatly facilitated by the ability to introduce cloned DNA into M. xanthus to generate gene replacement and merodiploid strains. However, gene replacement strains are difficult to obtain when the region(s) of homology between the cloned DNA and the M. xanthus chromosome is limited (less than 1 kilobase). We found that gene replacements can be obtained at an increased frequency by a two-step procedure involving the use of bacteriophage P1 to isolate merodiploid strains followed by generalized transduction to another M. xanthus strain by using phage Mx4. PMID- 3090024 TI - A conformationally altered precursor to the lysosomal enzyme alpha-mannosidase accumulates in the endoplasmic reticulum in a mutant strain of Dictyostelium discoideum. AB - The mutant strain of Dictyostelium discoideum, HMW-437, contains a mutation in the structural gene coding for the lysosomal enzyme alpha-mannosidase. Unlike the wild type strain, Ax3, this strain fails to proteolytically process or secrete the 140,000-dalton alpha-mannosidase precursor. The level of sulfate incorporation into the mutant precursor was significantly lower when compared to the wild type precursor. In addition, the mutant precursor was entirely sensitive to endoglycosidase H. Subcellular fractionation of HMW-437 membranes indicated that the majority of the alpha-mannosidase precursor sedimented in a region of the gradient corresponding to the rough endoplasmic reticulum. This accumulation within the rough endoplasmic reticulum did not appear to result from gross conformational changes which lead to aggregation. Trypsin digestion of radioactively labeled Ax3 and HMW-437 precursors demonstrated that there were differences in susceptibility to protease cleavage between the wild type and mutant alpha-mannosidase precursor molecules, suggesting that a minor conformational change could contribute to the accumulation of the mutant precursor inside the endoplasmic reticulum. PMID- 3090025 TI - Characterization of the pathways for phosphatidylethanolamine biosynthesis in Chinese hamster ovary mutant and parental cell lines. AB - A tritium suicide procedure was devised to facilitate the isolation of Chinese hamster ovary cell mutants defective in phosphatidylethanolamine biosynthesis. One mutant with a 20-50% reduction in [3H]ethanolamine incorporation was chosen for further analysis and was shown to have reduced activity of CTP: phosphoethanolamine cytidylyltransferase. Levels of phosphatidylethanolamine and rates of its biosynthesis were compared in the mutant and parent cell lines. Despite the reduced activity of the CDP-ethanolamine pathway in the mutant, levels of phosphatidylethanolamine were the same in mutant and parent cells. Rates of phosphatidylethanolamine synthesis de novo, as measured by incorporation of 32PO4 into phosphatidylethanolamine, were also the same in mutant and parent cells, as was the rate of incorporation of [3H]serine into both phosphatidylserine and phosphatidylethanolamine. After a long term labeling with [3H]serine, the specific radioactivity of phosphatidylserine was the same as that of phosphatidylethanolamine, and there was no difference in the specific radioactivities of the two lipids between mutant and parent cells. These results implicate decarboxylation of phosphatidylserine as the sole route for synthesis of phosphatidylethanolamine under normal culture conditions. PMID- 3090026 TI - Regulation of apo-A-I processing in cultured hepatocytes. AB - Apo-A-I, the major protein component of high density lipoproteins, appears intracellularly as an intermediate precursor (pro-apo-A-I) with a hexapeptide extension (RHFWQQ) at its amino terminus. Proteolytic processing of pro-apo-A-I to apo-A-I has been shown to occur extracellularly in cell and organ cultures from rat and human tissues. Recently, however, intracellular conversion has been detected in chickens. To determine what distinguishes and regulates these two processing methods, the proteolytic processing and secretion of apo-A-I was studied by metabolic labeling in chick hepatocytes and in Hep-G2 cells (derived from a human hepatocellular carcinoma). The proportions of intracellular and secreted pro-apo-A-I and apo-A-I were measured by sequencing NH2-terminal portions of the proteins and determining the location of radio-labeled amino acids. Chick hepatocytes cultured in the absence of hormones or fetal bovine serum secreted primarily processed apo-A-I (83%). In the presence of serum these cells secreted only pro-apo-A-I, whereas incubation with a combination of hormones (insulin, triiodothyronine, dexamethasone) resulted in secretion of a nearly equal mixture of the pro- and processed forms of the protein. In contrast, Hep-G2 cells, maintained in the absence of serum, secreted only pro-apo-A-I; when grown in the presence of serum these cells secreted a mixture of pro- and processed apo-A-I. Under conditions in which chick hepatocytes and Hep-G2 cells secreted both forms of the protein, a mixture of pro- and processed apo-A-I was also found intracellularly; when only the pro-form was secreted, the cells likewise contained only pro-apo-A-I. Under all the above conditions, the secreted apo-A-I exhibited similar isoform patterns in two-dimensional gel electrophoresis. These data show that both chick hepatocytes and human hepatoma cells are capable of intracellularly processing pro-apo-A-I to apo-A-I, and that the extent of intracellular processing is controlled by the cell's hormonal environment. PMID- 3090027 TI - Isolation and characterization of a new hemoglobin derivative cross-linked between the alpha chains (lysine 99 alpha 1----lysine 99 alpha 2). AB - Bis(3,5-dibromosalicyl) fumarate and a number of related bifunctional reagents react preferentially with oxyhemoglobin to cross-link the beta chains within the 2,3-diphosphoglycerate-binding site. In this report we describe a new derivative cross-linked between the alpha chains which is formed specifically in the reaction with deoxyhemoglobin. X-ray crystallographic studies show that the cross link lies between Lys-99 alpha 1 and Lys-99 alpha 2, spanning the central cavity of the tetramer. Lys-99 alpha 1 and Lys-99 alpha 2 are located within a cluster of charged residues very near the middle of the hemoglobin molecule. In oxyhemoglobin, this site is completely inaccessible to the cross-linking agent. Competition experiments with inositol hexaphosphate indicate that the compound enters the central cavity in deoxyhemoglobin through the cleft between the alpha chains. Despite the presence of the cross-link between the alpha chains, the modified hemoglobin remains highly cooperative. The Hill coefficient for HbXL99 alpha is 2.6. The oxygen affinity of the cross-linked derivative is decreased by approximately 2-fold; at pH 7.0 in the presence of 0.1 M NaCl the P50 is 13.9 mm Hg compared to 6.6 mm Hg for HbA. This difference appears to be due to relatively small changes in both KR, the association constant for binding of oxygen to the R state, and the allosteric constant L. Surprisingly, the isoelectric point of oxyHbXL99 alpha is almost identical to that of oxyHbA, whereas in the deoxy form the isoelectric point of the cross-linked derivative is decreased relative to native hemoglobin as expected due to the loss of the two positive charges of the modified amino groups. In agreement with these findings, the alkaline Bohr effect of HbXL99 alpha is decreased by more than 50%. Earlier studies argue strongly against the possibility that Lys-99 alpha is directly responsible for this large fraction of the Bohr effect in HbA. Analysis of the structure suggests that in the cross-linked derivative Glu-101 beta, which is in close proximity to Lys-99 alpha in oxyhemoglobin, becomes an acid Bohr group. PMID- 3090028 TI - Bacterial anion exchange. Use of osmolytes during solubilization and reconstitution of phosphate-linked antiport from Streptococcus lactis. AB - Membranes of Streptococcus lactis were solubilized with 1.1% octyl-beta-D glucopyranoside in the presence of 0.37% acetone/ether-washed phospholipid from several sources. After adding excess Escherichia coli phospholipid as bath sonicated liposomes, phosphate:sugar phosphate antiport was reconstituted in proteoliposomes by a 25-fold dilution in 0.1 M KPi (pH 7). Assays of 32Pi:Pi exchange showed that antiport was subject to an inactivation which varied in severity according to the lipid present at solubilization. Recovery of Pi-linked exchange was improved by the presence of 10-20% glycerol or other osmolyte during extraction. The osmolytes tested in this regard have included polyols (glycerol, erythritol, xylitol, sorbitol), sugars (glucose, trehalose), and two amino acids (glycine, proline). Each gave 10--20-fold increased recoveries of 32Pi:Pi antiport compared to controls using only detergent and lipid; these precautions were not required for the efficient reconstitution of F0F1-ATPase. Antiport in the artificial system was studied most carefully when glycerol was the stabilizing additive. For that case, the Kt values for Pi or 2-deoxyglucose 6 phosphate transport (275 and 25 microM, respectively) were the same as in native membranes. Maximal rates of Pi and 2-deoxyglucose 6-phosphate transport (200 and 42 nmol/min/mg of protein, respectively) and the turnover number for Pi exchange (25--50/s) suggested that antiporters were recovered without loss of activity. We conclude that the quantitative aspects of bacterial anion exchange are amenable to study in an artificial system, and that the use of osmolytes as general stabilants can be a valuable adjunct to current techniques for reconstitution of integral membrane transport proteins. PMID- 3090029 TI - Nonessentiality of histidine 291 of Rhodospirillum rubrum ribulose-bisphosphate carboxylase/oxygenase as determined by site-directed mutagenesis. AB - Chemical modification of spinach ribulosebisphosphate carboxylase/oxygenase by diethyl pyrocarbonate led to the conclusion that His-298 is an essential active site residue (Igarashi, Y., McFadden, B. A., and El-Gul, T. (1985) Biochemistry 24, 3957-3962). From the pH dependence of inactivation, the pKa of His-298 was observed to be approximately 6.8, and it was suggested that this histidine might be the essential base that initiates catalysis (Paech, C. (1985) Biochemistry 24, 3194-3199). To explore further the possible function of His-298, we have used site-directed mutagenesis to replace the corresponding residue of the Rhodospirillum rubrum carboxylase (His-291) with alanine. Assays of extracts of Escherichia coli JM107, harboring either the wild-type or mutant gene in an expression vector, revealed that the mutant protein is approximately 40% as active catalytically as the normal carboxylase. After purification to near homogeneity by immunoaffinity chromatography, the mutant protein was partially characterized with respect to subunit structure, kinetic parameters, and interaction with a transition-state analogue. The purified mutant carboxylase had a kcat of 1.5 s-1 and a kcat/Km of 1.7 X 10(4) M-1 s-1 in contrast to values of 3.6 s-1 and 6 X 10(5) M-1 s-1 for the normal enzyme. The high level of enzyme activity exhibited by the Ala-291 mutant excludes His-291 in the R. rubrum carboxylase (and by inference His-298 in the spinach carboxylase) as a catalytically essential residue. PMID- 3090030 TI - Hydrolysis of 4-nitrophenyl acetate catalyzed by carbonic anhydrase III from bovine skeletal muscle. AB - We report three experiments which show that the hydrolysis of 4-nitrophenyl acetate catalyzed by carbonic anhydrase III from bovine skeletal muscle occurs at a site on the enzyme different than the active site for CO2 hydration. This is in contrast with isozymes I and II of carbonic anhydrase for which the sites of 4 nitrophenyl acetate hydrolysis and CO2 hydration are the same. The pH profile of kcat/Km for hydrolysis of 4-nitrophenyl acetate was roughly described by the ionization of a group with pKa 6.5, whereas kcat/Km for CO2 hydration catalyzed by isozyme III was independent of pH in the range of pH 6.0-8.5. The apoenzyme of carbonic anhydrase III, which is inactive in the catalytic hydration of CO2, was found to be as active in the hydrolysis of 4-nitrophenyl acetate as native isozyme III. Concentrations of N-3 and OCN- and the sulfonamides methazolamide and chlorzolamide which inhibited CO2 hydration did not affect catalytic hydrolysis of 4-nitrophenyl acetate by carbonic anhydrase III. PMID- 3090031 TI - N-glycohydrolysis of adenosine diphosphoribosyl arginine linkages by dinitrogenase reductase activating glycohydrolase (activating enzyme) from Rhodospirillum rubrum. AB - The reaction catalyzed by the activating enzyme for dinitrogenase reductase from Rhodospirillum rubrum has been studied using an ADP-ribosyl hexapeptide, obtained from proteolysis of inactive dinitrogenase reductase, and synthetic analogs such as N alpha-dansyl-N omega-ADP-ribosylarginine methyl ester. The activating enzyme catalyzed N-glycohydrolysis of the ribosyl-guanidinium linkage releasing ADP ribose and regenerating an unmodified arginyl guanidinium group. Optimal glycohydrolysis of the low molecular weight substrates occurred at pH 6.6 and required 1 mM MnCl2, but did not require ATP. The ADP-ribosyl hexapeptide (Km 11 microM), N alpha-dansyl-N omega-ADP-ribosylarginine methyl ester (Km 12 microM), N alpha-dansyl-N omega-ADP-ribosylarginine (Km 12 microM), N alpha-dansyl-N omega 1,N6-etheno-ADP-ribosylarginine methyl ester (Km 11 microM), and N alpha-dansyl-N omega-GDP-ribosylarginine methyl ester (Km 11 microM) were comparable substrates. N omega-ADP-ribosylarginine (Km 2 mM) was a poor substrate, and the activating enzyme did not catalyze N-glycohydrolysis of N alpha-dansyl-N omega-5' phosphoribosylarginine methyl ester or N alpha-dansyl-N omega-ribosylarginine methyl ester. 13C NMR of N alpha-tosyl-N omega-ADP-ribosylarginine methyl ester established that the activating enzyme specifically hydrolyzed the alpha-ribosyl guanidinium linkage. The beta-linked anomer was hydrolyzed only after anomerization to the alpha configuration. We recommend [arginine(N omega-ADP alpha-ribose)]dinitrogenase reductase N-glycohydrolase (dinitrogenase reductase activating) and dinitrogenase reductase activating glycohydrolase as the systematic and working names for the activating enzyme. PMID- 3090032 TI - Calcium fluxes and calcium buffering in human neutrophils. AB - Neutrophils loaded with the calcium indicator quin-2 and challenged with the ionophore ionomycin or the chemotactic peptide fMet-Leu-Phe were examined in the light of a theory that relates time-dependent changes in the fluorescence of the indicator to cytosolic calcium fluxes and levels. The cytosolic binding capacity was estimated from the theory to be 1.5 +/- 0.6 X 10(8) sites/cell (0.76 mM based on a cell volume of 330 micron 3, irrespective of water content and the distribution of sites), each site having an apparent average single class dissociation constant of 0.55 +/- 0.2 microM. Some 20% of the total available cytosolic calcium sites of the normal resting cell appear to be occupied when no quin-2 is present. In a calcium-free medium, the amount of calcium released by fMet-Leu-Phe from storage pool locations that are distinct from the cytosolic sites is sufficient to further raise the cytosolic site occupancy level to 50%, at which point the calcium buffering capacity of the cytosol is maximal. In a calcium-containing medium, however, simultaneous influx from the outside appears to supply enough additional calcium to saturate most of the remaining sites. The combined initial rate of storage pool calcium release plus influx through the plasma membrane was roughly twice the initial rate at which calcium was released from storage locations alone, suggesting that stimulus-induced influx from the outside may be comparable in importance to storage pool mobilization in determining physiological calcium levels in stimulated cells. PMID- 3090034 TI - Reaction intermediate partitioning by ribulose-bisphosphate carboxylases with differing substrate specificities. AB - The carboxylated, 6-carbon reaction intermediate (3-keto-2-carboxyarabinitol 1,5 bisphosphate) from the ribulose-1,5-bisphosphate carboxylase reaction was obtained by denaturing the enzyme with acid during steady-state turnover. Carbon 13 NMR analysis indicates that this beta-keto acid exists in solution predominantly as the C-3 ketone (as opposed to the hydrate) form. In neutral solution the intermediate slowly decomposes (t1/2 approximately 1 h) by decarboxylation. This decarboxylation reaction is catalyzed by nonactivated (metal free) ribulose-1,5-bisphosphate carboxylase. Alternately, the activated enzyme predominantly catalyzes the hydrolysis of the intermediate to two molecules of glycerate 3-phosphate. The partitioning of the intermediate (i.e. hydrolysis/(hydrolysis + decarboxylation] by activated ribulose-1,5-bisphosphate carboxylase was studied using enzymes from three different sources and with different activating metal atoms. This afforded a series of catalysts whose relative specificities for the alternate substrates, carbon dioxide and oxygen, varied over a 50-fold range. When Mg2+ was the activating metal, the partitioning of the reaction intermediate varied only from 0.93 to 1 for all three enzymes. Even the Co2+ activated enzyme from Rhodospirillum rubrum, which is completely devoid of carboxylase activity, partitioned approximately 30% of added intermediate to products. It is probable that the 6-carbon intermediate's strong commitment to product formation is paralleled by a similarly strong forward commitment of the analogous intermediate in the oxygenase reaction. In this event, the variations in relative specificity for the gaseous substrates of enzymes from different natural sources must arise by interactions that take place on the enzyme prior to the formation of the intermediates. PMID- 3090033 TI - Determination of the signal peptidase cleavage site in the preprosubtilisin of Bacillus subtilis. AB - Bacillus subtilis subtilisin is predicted to be synthesized as a preproenzyme according to the sequence analysis of its gene. We have synthesized the [35S] methionine-labeled preprosubtilisin in vitro and processed the precursor to prosubtilisin by the addition of membrane vesicles derived from vegetative cells of B. subtilis and Triton X-100. Radiosequencing of the prosubtilisin allowed the precise determination of the signal peptidase cleavage site. The preprosubtilisin was found to have a 29-amino-acid-long signal peptide with the signal peptidase cleavage sequence of AlaGln-AlaAla. Fusion of the signal peptide sequence to the mature TEM beta-lactamase structural gene allowed the production of an active and secreted form of beta-lactamase in vivo. An N-terminal sequence analysis of this product indicated that the observed in vivo signal peptidase cleavage site was exactly the same as that determined by in vitro analysis. During the development of the in vitro processing system, we demonstrated that the replacement of the subtilisin transcription regulatory sequence by a vegetative promoter allowed the vegetative expression and secretion of subtilisin. Thus, the late expression of the native subtilisin gene is mainly controlled at the transcription level and the secretion/processing systems are available for vegetative production of subtilisin. PMID- 3090036 TI - Horseradish peroxidase-catalyzed conversion of iodine to iodide in presence of EDTA and H2O2. AB - EDTA (4 mM) blocks the oxidation of iodide to I-3 (increase of extinction at 353 nm) by H2O2 catalyzed by horseradish peroxidase, which is reversed by the addition of an equimolar concentration of Zn2+. Addition of suboptimal concentration of EDTA (2 mM) not only decreases the rate of forward reaction of I 3 formation but also causes loss of extinction of the same when I-3 is generated. The loss of extinction of I-3 is proportional to the enzyme concentration and is blocked by azide, the inhibitor of the peroxidase. EDTA also causes bleaching of nonenzymatically formed I-3 (from iodide and H2O2) only in the presence of horseradish peroxidase, and the effect is reversed by the equimolar concentration of Zn2+. Both the bleaching of I-3 by EDTA and reversal of EDTA effect by Zn2+ are sensitive to azide. The decrease of extinction of I-3 (formed by dissolving iodine in KI solution) is dependent on EDTA, H2O2, and horseradish peroxidase. Molecular iodine is also bleached but at a slower rate than I-3. Evidence is presented to show that this bleaching of I-3 is due to enzymatic conversion of I 3 to iodide in presence of EDTA and H2O2 and this involves pseudocatalatic degradation of H2O2 to O2. PMID- 3090035 TI - Purification to apparent homogeneity of the mating pheromone of mat-1 homozygous Euplotes raikovi. AB - Mating type-specific mating pheromones autonomously released into the environment control cell-cell union in conjugation of the marine ciliate Euplotes raikovi. The mating pheromone, termed euplomone r-1, of cells of the homozygous mating type determined by the mat-1/mat-1 genotype was purified by means of a three stage purification procedure which provides a yield of 79%. Starting from 10 liters of supernatant, 3.3 mg of euplomone r-1 were regularly recovered. Euplomone r-1 was identified with a protein showing a molecular weight of 12,000, an isoelectric point of 3.7, and unusually high contents of cysteine (15%) and tyrosine (5.8%). It appeared active at a concentration of 3.4 +/- 0.5 X 10(-12) M. Carbohydrate and a small colored compound, not yet identified, occurred in association with partially purified euplomone r-1 samples, whereas they were not detected in samples of the final product of purification. An acidic shift was apparently capable of destroying the carbohydrate/euplomone r-1 association, suggesting that it does not involve covalent bonds. PMID- 3090037 TI - Characterization of a structural series of lipid A obtained from the lipopolysaccharides of Neisseria gonorrhoeae. Combined laser desorption and fast atom bombardment mass spectral analysis of high performance liquid chromatography purified dimethyl derivatives. AB - Monophosphoryl lipid A (MLA) obtained from the lipopolysaccharides of serum sensitive strains of Neisseria gonorrhoeae was fractionated on a silicic acid column to yield the hexaacyl and pentaacyl MLAs. The dimethyl derivative of the hexaacyl MLA was analyzed by proton nuclear magnetic resonance spectroscopy. The dimethyl esters of hexaacyl and pentaacyl MLAs were further purified by reverse phase high performance liquid chromatography, and all of the peaks were analyzed by laser desorption mass spectrometry. Considerable structural information was obtained by laser desorption mass spectrometry due to three kinds of specific fragmentations of the sugar at the reducing end. Two major fractions were also analyzed by positive ion fast atom bombardment mass spectrometry. High performance liquid chromatography was able to separate the dimethyl MLA according to number, nature, and position of the fatty acyl groups. Since almost no structural information is available, the mass spectra of the samples were interpreted on the basis of the established structure of a model lipid A (hexaacyl MLA derived from Salmonella minnesota). Thirteen different structures of dimethyl MLA were identified. The four prominent dimethyl MLAs found in the fractionated samples were M1 (Mr = 1463), M2 (Mr = 1479), M3 (Mr = 1661), and M4 (Mr = 1677). These MLAs appear to have a 1'----6 linked glucosamine disaccharide backbone. The most prominent hexaacyl MLA was M3. We propose that it contains hydroxylaurate at the 3- and 3'-positions in ester linkage and lauroxymyristate at the 2- and 2'-positions in amide linkage of the glucosamine disaccharide. The most abundant pentacyl MLA was M2. We propose that it contains hydroxylaurate at the 3- and 3'-positions in ester linkage, lauroxymyristate at the 2'-position in amide linkage, and hydroxymyristate at the 2-position in amide linkage of the disaccharide. The lipid A of N. gonorrhoeae appeared to differ from that of the Salmonella strains by the presence of shorter-chain fatty acids and by the normal fatty acid distribution in the reducing and distal subunits. PMID- 3090038 TI - DNA ligase from Drosophila melanogaster embryos. Purification and physical characterization. AB - A DNA ligase has been purified approximately 2,100-fold, to near-homogeneity, from Drosophila melanogaster 6-12-h embryos and was shown to catalyze the formation of 3',5'-phosphodiester bonds. Polypeptides with molecular weights 83,000, 75,000, and 64,000 were observed when the purified enzyme was electrophoresed under denaturing conditions. These polypeptides were shown by partial proteolysis studies and two-dimensional gel analysis to be structurally related. The two smaller polypeptides were presumably derived from the largest, 83,000 molecular weight protein, by proteolysis during purification or in vivo. All three polypeptides formed enzyme-adenylylate complexes in the absence of DNA. Drosophila DNA ligase had a Stokes radius of 45 A, a sedimentation coefficient of 4.3 S, and a frictional ratio of 1.6, yielding a calculated molecular weight of 79,800. These studies indicate that DNA ligase from Drosophila embryos is a monomer. The purified ligase was free of detectable ATPase, nuclease, topoisomerase, and DNA polymerase activities. The enzyme exhibited an absolute requirement for ATP in the joining reaction. A divalent metal was required and N ethylmaleimide inhibited the reaction. Formation of phosphodiester bonds by Drosophila ligase required the presence of 5'-phosphoryl and 3'-hydroxyl termini. The purified enzyme restored biological activity to endonucleolytically cleaved pBR322 DNA. The specific activity of Drosophila DNA ligase was highest in unfertilized eggs. Developing embryos had 5-10-fold more ligase activity than at any later time in development. PMID- 3090039 TI - Increased response to insulin of glucose metabolism in the 6-day unloaded rat soleus muscle. AB - Hind leg muscles of female rats (85-99 g) were unloaded by tail cast suspension for 6 days. In the fresh-frozen unloaded soleus, the significantly greater concentration of glycogen correlated with a lower activity ratio of glycogen phosphorylase (p less than 0.02). The activity ratio of glycogen synthase also was lower (p less than 0.001), possibly due to the higher concentration of glycogen. In isolated unloaded soleus, insulin (0.1 milliunit/ml) increased the oxidation of D-[U-14C]glucose, release of lactate and pyruvate, incorporation of D-[U-14C]glucose into glycogen, and the concentration of glucose 6-phosphate more (p less than 0.05) than in the weight-bearing soleus. At physiological doses of insulin, the percent of maximal uptake of 2-deoxy-D-[1,2-3H]glucose/muscle also was greater in the unloaded soleus. Unloading of the soleus increased by 50% the concentration of insulin receptors, due to no decrease in total receptor number during muscle atrophy. This increase may account for the greater response of glucose metabolism to insulin in this muscle. The extensor digitorum longus, which generally shows little response to unloading, displayed no differential response of glucose metabolism to insulin. PMID- 3090040 TI - Binding of plasminogen to extracellular matrix. AB - We have previously demonstrated that plasminogen immobilized on various surfaces forms a substrate for efficient conversion to plasmin by tissue plasminogen activator (t-PA) (Silverstein, R. L., Nachman, R. L., Leung, L. L. K., and Harpel, R. C. (1985) J. Biol. Chem. 260, 10346-10352). We now report the binding of human plasminogen to the extracellular matrix synthesized in vitro by cultured endothelial cell monolayers. The binding was specific, saturable at plasma plasminogen concentrations, reversible, and lysine-binding site-dependent. Functional studies demonstrated that matrix immobilized plasminogen was a much better substrate for t-PA than was fluid phase plasminogen as shown by a 100-fold decrease in Km. Activation of plasminogen by t-PA and urokinase on the matrix was equally efficient. The plasmin generated on the matrix, in marked contrast to fluid phase, was protected from its fast-acting inhibitor, alpha 2-plasmin inhibitor. Matrix-associated plasmin converted bound Glu- into Lys-plasminogen, which in turn is more rapidly activated to plasmin by t-PA. The extracellular matrix not only binds and localizes plasminogen but also improves plasminogen activation kinetics and prolongs plasmin activity in the subendothelial microenvironment. PMID- 3090041 TI - Interactions of the Escherichia coli methionine repressor with the metF operator and with its corepressor, S-adenosylmethionine. AB - The metJ gene encoding the methionine aporepressor was placed under the control of a strong and inducible promoter, ptac. Bacterial strains carrying the recombinant plasmid pIP35 overproduced the regulatory protein by a factor of 200 over the wild type strain as determined by the immunoblot technique. The purified metJ gene product negatively controls the expression of the metF gene, in a cell free system as shown by repression of beta-galactosidase synthesis under the control of the metF promoter. The metJ protein binds to a DNA fragment containing the potential operator of the metF gene with an affinity which is 10 times greater in the presence of S-adenosylmethionine than in its absence. Equilibrium dialysis experiments showed that the met aporepressor binds 2 mol of S adenosylmethionine per mol of dimer with a dissociation constant of 200 microM. PMID- 3090042 TI - The effects of metal ions and temperature on the interaction of cobra venom factor and human complement factor B. AB - An alternative pathway C3 convertase is formed by the equilibrium association of Factor B with cobra venom factor (CVF) followed by the activation step catalyzed by Factor D. However, the association of Factor B with CVF has only occasionally been demonstrated and has not been quantitatively analyzed. Here we show that in the absence of metals the two proteins have significant affinity for each other and reversibly associate in a one-to-one stoichiometry with a dissociation constant of 11.6 microM. Upon the addition of metal ions, the complex is stabilized only 2- to 30-fold in the order Ni2+(Kd = 6.6 microM) less than Mg2+(Kd = 1.1 microM) less than Mn2+(Kd = 0.4 microM). These results suggest that metal ions may be less important in stabilizing the CVF.B complex and more important in promoting the subsequent equilibrium association of CVF.B with Factor D. The stability of the CVF.B complex is variously dependent on temperature in the range studied (14-21 degrees C) depending on the metal ion that is present. The complex formation was demonstrated in the analytical ultracentrifuge at sedimentation equilibrium employing a combination of single- and multiple-independent variable nonlinear least squares analytical techniques. Two different numerical approaches gave very similar results. PMID- 3090043 TI - Amino acid sequence of the pyruvate and the glyoxylate active-site lysine peptide of Escherichia coli 2-keto-4-hydroxyglutarate aldolase. AB - Pure 2-keto-4-hydroxyglutarate aldolase of Escherichia coli, a "lysine-type" trimeric enzyme which has the unique properties of forming an "abortive" Schiff base intermediate with glyoxylate (the aldehydic product/substrate) and of showing strong beta-decarboxylase activity toward oxalacetate, binds any one of its substrates (2-keto-4-hydroxyglutarate, pyruvate, or glyoxylate) in a competitive manner. To determine whether the substrates bind at the same or different (juxta-positioned) sites and what degree of homology might exist between the active-site lysine peptide of this enzyme and that of other lysine type (Class I) aldolases or beta-decarboxylases, the azomethine formed separately by this aldolase with either [14C]pyruvate or [14C]glyoxylate was reduced with CNBH3-. After each enzyme adduct was digested with trypsin, the 14C-labeled peptide was isolated, purified, and subjected to amino acid analysis and sequence determination. In each case, the same 14-amino acid lysine-peptide was isolated and found to have the following primary sequence: Glu-Phe-*Lys-Phe-Phe-Pro-Ala Glu-Ala-Asn-Gly-Gly-Val-Lys (where * = the active-site lysine). Hence, glyoxylate competes for, and inhibits aldolase activity by reacting with, the one active site lysine residue/subunit. This active-site lysine peptide has a high degree (65%) of homology with that of 2-keto-3-deoxy-6-phosphogluconate aldolase of Pseudomonas putida but is not similar to that of any Class I fructose-1,6 bisphosphate aldolase or of acetoacetate beta-decarboxylase of Clostridium acetobutylicum. Furthermore, it was found that extensive reaction of glyoxylate with the N-terminal amino group of this enzyme may well be general complicating factor in sequence studies with proteins plus glyoxylate. PMID- 3090044 TI - The interaction of nucleotides with pertussis toxin. Direct evidence for a nucleotide binding site on the toxin regulating the rate of ADP-ribosylation of Ni, the inhibitory regulatory component of adenylyl cyclase. AB - The interaction of nucleotides with pertussis toxin (PT), and their effects on the ability of the toxin to ADP-ribosylate pure Ni, were evaluated. [32P]ATP (10 nM) bound directly to dithiothreitol-activated PT. This binding was competitively inhibited by nucleotides and anions with the following IC50 concentrations in order of decreasing potency: ATP = ATP gamma S (adenosine-5'-O-(3 thiotriphosphate)) = 0.2-0.3 microM, GDP beta S (guanosine-5'-O-(2 thiodiphosphate)) = 2-3 microM, GTP gamma S (guanosine-5'-O-(3-thiotriphosphate)) = 10-15 microM, ADP = 20-25 microM, GTP = 30-40 microM, GMP-P(NH)P (guanyl-5'-yl imidodiphosphate) = 100-150 microM, GDP = 150-200 microM, Pi = SO4(2-) = 20 mM and Cl- = acetate = 30-35 mM. Treatment of PT with ATP, AMP-P(NH)P, GTP, GDP, or GDP beta S, resulted in a stimulated state of NAD+-Ni ADP-ribosyltransferase activity. Addition of ATP, AMP-P(NH)P (adenyl-5'-yl imidodiphosphate), GTP, GDP, and GDP beta S to the ADP-ribosylation reactions resulted in increased rates of ADP-ribosyl-Ni formation. It is concluded that these effects on the nucleotides are due to their action to stimulate the activity of PT. At concentrations of PT between 0.04 and 0.4 microgram/ml, the stimulation of ADP-ribosylation of Ni effected by nucleotides was hysteretic in nature, exhibiting an approximately 25 min long lag when GDP was used as the activating nucleotide. These lags decreased with increasing concentrations of PT, and were abolished by pretreatment of the toxin with GDP or ATP. Preliminary incubation of Ni with GDP had no effect on the lag in its ADP-ribosylation by non-nucleotide treated PT. Addition of divalent cations (Mg2+, Mn2+, and Ca2+) inhibited formation of ADP-ribosyl-Ni, possibly by causing aggregation and denaturation of Ni. This is the first demonstration that both adenine and guanine nucleotides interact directly with PT and act to stimulate its activity to ADP-ribosylate Ni, and that guanine nucleotides do so regardless of whether they are nucleoside di- or triphosphates. PMID- 3090045 TI - Purification and characterization of a plasminogen activator inhibitor from the histiocytic lymphoma cell line U-937. AB - We report the production, purification, characterization, and partial amino acid sequence of a plasminogen inhibitor (PA-I). The starting material is culture fluid from phorbol myristate 13-acetate-treated U-937 cells and the isolation steps consist of preparative isoelectric focusing followed by affinity chromatography on Cibacron Blue-Sepharose. PA-I migrates as a closely spaced doublet of 47-kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and forms covalent complexes with urokinase and two-chain tissue-type plasminogen activator, displaying second order rate constants of 0.9 X 10(6) M-1 s-1 and 0.2 X 10(6) M-1 s-1, respectively. Upon treatment with 1 M NH4OH, the covalent complexes were hydrolyzed, yielding a 35-kDa inhibitor fragment. A partial amino acid sequence of PA-I showed that it belongs to the antithrombin III family of inhibitors. PA-I is immunologically related to a PA-inhibitor from human placenta. mRNA from phorbol myristate 13-acetate-treated U-937 cells directed, in a rabbit reticulocyte derived cell-free system, the biosynthesis of only one 47 kDa protein that could be immunoprecipitated with anti-PA-I IgG, indicating that the two molecular forms of PA-I are the products of post-translational processing. PMID- 3090046 TI - Isolation and characterization of a lysine-specific protease from Pseudomonas aeruginosa. AB - We report here a procedure which results in the purification of an extracellular protease (designated Ps-1) from Pseudomonas aeruginosa. This enzyme cleaves fibrinogen so that the modified molecules form microcrystals and large single crystals. Precise knowledge of the Ps-1 cleavage sites is essential for the interpretation of the structural information provided by these crystals (Weisel, J. W., Stauffacher, C. V., Bullitt, E., and Cohen, C. (1985) Science 230, 1388 1391). Ps-1 is a single-chain polypeptide of Mr 30,000 which appears to function as a monomer. The pH optimum is 8-9. The activity of the protease is not decreased by inhibitors of thiol, carboxyl, or metallo proteases; the abolishment of activity by N alpha-p-tosyl-L-lysine chloromethyl ketone and the partial inhibition obtained with serine-reactive inhibitors suggests that Ps-1 may be a serine protease with an unusual active-site conformation. Studies with synthetic peptide substrates show that Ps-1 exhibits one of the most restricted specificities known for an endoproteinase: only peptide, ester, and amide bonds containing the carbonyl group of lysine are hydrolyzed. The limited specificity of Ps-1 should make it useful for other applications requiring the selective cleavage of proteins, such as sequence analysis and the isolation of domains. PMID- 3090047 TI - Mutagenesis of ligands to the [4 Fe-4S] center of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase. AB - Several mutations were constructed in residues thought to provide ligands for a [4Fe-4S] cluster in Bacillus subtilis amidophosphoribosyltransferase using site directed mutagenesis of cloned purF. These replacements confirm the identification of cysteinyl ligands to the Fe-S center. Of five mutant enzymes, two had no activity, two less than 25% of the wild type activity, and one was lethal and could not be studied. The Fe content of the two mutant enzymes with partial activity was similar to that of the wild type. Results of partial characterization suggest that the [4Fe-4S] cluster is not involved in allosteric regulation and does not play a specific role in the ammonia- or glutamine dependent reactions of the enzyme. At least partial enzymatic activity is required for NH2-terminal processing. Pulse labeling experiments suggest that processing is a slow post-translational process which is dependent upon cellular factors. A relationship between Fe-S centers and NH2-terminal processing of an undecapeptide leader suggests a functional connection between these two structural elements in amidophosphoribosyltransferase. PMID- 3090048 TI - Results of operative treatment of displaced external rotation-abduction fractures of the ankle. PMID- 3090049 TI - A prospective trial comparing operative and manipulative treatment of ankle fractures. AB - A series of 42 ankle fractures have been randomised into two groups respectively undergoing either open reduction and internal fixation or manipulative reduction and plaster. Their progress after removal of all external splintage has been followed using simple gait analysis techniques. There appears to be no difference in the outcome of treatment of the two groups in the early recovery period (up to 20 weeks). PMID- 3090050 TI - Potentiation of the chemotherapeutic action of tegafur against solid adenocarcinoma 755 by combination with L-cystine. AB - The chemotherapeutic action of tegafur (FT) against adenocarcinoma 755 in mice was markedly potentiated by oral administration of L-cysteine and L-cystine without increasing its toxicity. In particular, the combination of FT at 200 mg/kg per day (maximum dose) and 1000 mg/kg per day of L-cystine markedly inhibited tumor growth. The dose ratio of L-cysteine or L-cystine to FT needs 5 by weight to potentiate the antitumor activity of FT. The antitumor activity of 5 fluorouracil (FU) was slightly, but not significantly, increased by L-cysteine. The total concentration of FT in the plasma and the tumor when it was given in combination with L-cystine was significantly increased when compared with FT alone 1 h after oral administration. The FU level in the plasma after administration of the combination of FT and L-cystine was three times higher than that after FT alone, and the FU level in the tumor after treatment with the combination of FT and L-cystine was also higher (about 20%) than that after FT alone. This significant increase in FT and FU levels in the plasma and the tumor may be related to the potentiation of the antitumor activity of FT by L-cystine. PMID- 3090051 TI - Recovery patterns of rat hemopoietic stem cells between pulse doses of 7,12 dimethylbenz(a)anthracene (DMBA) applied in a leukemogenic regimen. AB - Male Wistar rats received repeated pulse doses of 7,12-dimethylbenz(a)anthracene (DMBA), known to elicit myelodysplasia followed by acute, mostly erythroblastic, leukemia at 10-day intervals. The recovery of spleen colony forming hemopoietic stem cells (CFU-s) surviving the cytocidal action of DMBA was examined between pulses. Recovery after a pulse of 35 mg/kg body weight varied with the organ source of the CFU-s (femoral bone marrow or spleen) and the number of preceding DMBA pulses. After a single DMBA pulse bone marrow CFU-s initially recovered faster than reported for normal bone marrow CFU-s transplanted into chemically conditioned rats. But recovery was followed by regeneration arrest. Population doubling times of marrow CFU-s increased with the number of DMBA pulses. Recovery of splenic CFU-s was slower after a single DMBA pulse than reported for normal spleen CFU-s transplanted into chemically conditioned rats. The CFU-s population doubling times were not significantly different after a single or five DMBA pulses. After three pulses, however, recovery of splenic CFU-s was exceedingly slow until day 5 and subsequently accelerated, but was still slower than after one or five pulses. In the spleen CFU-s recovery was always accompanied by regeneration of total cell numbers with a preference for erythroid regeneration. In the bone marrow this was the case after three DMBA pulses only. PMID- 3090052 TI - Agorins: major structural proteins of the plasma membrane skeleton of P815 tumor cells. AB - Plasma membranes of P815 mastocytoma cells contain a set of proteins that remain selectively insoluble upon extraction of the membranes with Triton X-100, and appear to form a membrane skeletal matrix independent of the filamentous cytoskeletal systems. EGTA treatment of the matrix was found to release approximately 25% of the protein as polypeptides of 70, 69, 38, and 36 kD, all of which appear to be peripheral components associated with the cytoplasmic face of the plasma membrane via divalent cation-dependent interactions. About 75% of the total matrix protein was recovered in the EGTA-insoluble fraction. Actin accounted for approximately 5% of the total protein in the EGTA-insoluble fraction. The rest was accounted for by two novel proteins of 20 and 40 kD which, despite their relatively low molecular weights, do not enter SDS PAGE gels. Together these proteins account for approximately 15% of the total plasma membrane protein, and are thus present in much higher amounts than any other characterized protein of nucleated cell plasma membranes. Based on the extensive associations of these proteins to form very large detergent-insoluble structures, we propose that they may be named agorin I, the 20-kD protein, and agorin II, the 40-kD protein, from the Greek agora meaning assembly. The amount and properties of these proteins and the appearance of the EGTA-insoluble material in thin section electron micrographs indicate that the agorins are the major structural elements of the membrane matrix, and thus of the putative membrane skeleton. PMID- 3090053 TI - Vinculin interaction with permeabilized cells: disruption and reconstitution of a binding site. AB - Fluorescently labeled vinculin binds to focal contact areas in permeabilized cells independent of actin (Avnur, Z., J. V. Small, and B. Geiger, 1983, J. Cell Biol., 96:1622-1630), but the nature of the binding site is unknown. In this study we have examined the interaction of vinculin with these sites in permeabilized L6 myoblasts to define conditions that perturb the binding and subsequently to reconstitute it. Mild treatment with low concentrations of protease prevents vinculin incorporation without gross changes in the cytoskeleton or extensive protein breakdown. Exposure to buffers of moderate ionic strength also reduces subsequent vinculin binding without large morphological effects. These extraction conditions were used to obtain a fraction from gizzard which was able to restore the vinculin localization. Talin, actin, and vinculin itself were able to alter the binding of labeled vinculin to permeabilized cells and each also interacted with vinculin in gel overlays; however, they were unable to reconstitute the binding site in treated permeabilized cells. The results show a requirement for an as yet unidentified protein to capacitate vinculin binding to focal contact sites and suggest that this protein is peripheral and interacts directly with the binding site. PMID- 3090054 TI - Binding of iodinated multipotential colony-stimulating factor (interleukin-3) to murine bone marrow cells. AB - Multipotential colony-stimulating factor (Multi-CSF or interleukin-3) was radioiodinated to high specific radioactivity (1-4 X 10(5) cpm/ng) with no detectable loss of biological activity and its binding to murine bone marrow cells and factor-dependent cell lines studied. Both the native glycosylated molecule purified from a cloned T-cell line (LB-3) and the purified non glycosylated recombinant molecule produced by E. coli could be radioiodinated. Comparative binding studies with these derivatives demonstrated equal binding affinities and equal numbers of binding sites on various cell types indicating that carbohydrate moieties are not involved in the binding interactions. Binding of 125I-Multi-CSF to several factor-dependent continuous hemopoietic cell lines showed the presence of specific receptors on all cell lines, the receptor number per cell varying from 700 to 13,000 and the apparent dissociation constant from 400 pM to 1 nM. Specific binding of 125I-Multi-CSF was also observed to normal murine hemopoietic cells and the binding to murine bone marrow cells was studied in detail. Bone marrow cells showed 117-130 receptors per cell on average and an apparent dissociation constant of 126-233 pM. However, quantitative autoradiographic analysis indicated that receptors for 125I-Multi-CSF were not distributed randomly on bone marrow cells--nucleated erythroid and lymphoid cells were not labeled while essentially all neutrophilic granulocyte, eosinophilic granulocyte and monocytic cells were labeled. Moreover, in each of the labeled cell lineages grain counts (reflecting receptor number) decreased with increasing maturation and a small subpopulation of marrow cells (0.4-1.5% and including blast cells, monocytes, promyelocytes, and myelocytes) exhibited very high grain counts. The existence of such a subset of marrow cells raises the possibility of functional heterogeneity among marrow cells in their response to Multi-CSF. PMID- 3090055 TI - Sensitization of rat hepatocytes to hyperthermia by calcium. AB - The viability of isolated rat hepatocytes, as assayed by trypan blue exclusion, decreases in a dose-dependent fashion during exposure to hyperthermia (D0 [43 degrees C] = 105 +/- 10 min, D0 [45 degrees C] = 24 +/- 4 min). Hyperthermic sensitivity varies as a function of extracellular Ca2+ concentration in a biphasic manner; optimum survival occurs at 1-5 mM Ca2+, with sensitization in the absence of Ca+ and increasing sensitization at Ca2+ concentrations greater than 10 mM. Ca influx does not correlate well with loss of viability for hepatocytes in 4 mM extracellular Ca2+; influx does not occur until viability decreases to less than 1%. Under sensitizing conditions, Ca2+ influx proceeds loss of viability. Influx begins within 15 min at 45 degrees C in 15 mM Ca2+, and the ionophore A23187 is a potent hyperthermic sensitizer in the presence of extracellular Ca2+. Thus, Ca2+ influx, whether caused by high extracellular Ca2+ or A23187, increases cellular damage caused by supraoptimal temperatures, although some Ca2+ is necessary for maximum resistance, probably because of stabilization of Ca2+ binding proteins against thermal denaturation or possibly to Ca2+-induced decrease in lipid fluidity. PMID- 3090056 TI - Development of a neural phenotype in differentiating ganglion cell-derived human neuroblastoma cells. AB - Human neuroblastoma cells (clone SHSY-5Y) induced to differentiate by 12-O tetradecanoylphorbol-13-acetate (TPA) are shown to possess properties characteristic of mature ganglion cells. Elevation of the external K+ concentration, exposure to Ca2+ ionophore A23187, and acetylcholine all stimulate the release of preloaded 3H-noradrenaline in the presence but not in the absence of added Ca2+. Acetylcholine causes a fall in the 86Rb+ or 14C-TPMP equilibrium potential across the plasma membrane and stimulates 86Rb+ efflux. These responses are prevented by atropine. Acetylcholine and muscarine but not nicotine stimulate an increase in 45Ca2+ influx, an effect blocked by atropine. None of these responses have been observed in nondifferentiating cells. Muscarinic receptors, however, as measured by the binding of tritiated quinuclidinyl benzilate (3H QNB), were present to a similar extent in control and differentiated cells. Both cell types also exhibit an accelerated release of Ca2+ in response to acetylcholine, but the control cells were at least 1 order of magnitude more sensitive to the agonist. PMID- 3090057 TI - The extracellular electrical current pattern and its variability in vitellogenic Drosophila follicles. AB - We determined the extracellular electrical current pattern around Drosophila follicles at different developmental stages (7-14) with a vibrating probe. At most stages a characteristic pattern can be recognized: current leaves near the oocyte end of the follicle and enters at the nurse cells. Only at late vitellogenic stages was an inward-directed current located at the posterior pole of many follicles. Most striking was the observed heterogeneity both in current pattern and in current density between follicles of the same stage. Different media (changed osmolarity or pH, addition of cytoskeletal inhibitors or juvenile hormone) were tested for their effects on extrafollicular currents. The current density was consistently influenced by the osmolarity of the medium but not by the other parameters tested. Denuded nurse cells (follicular epithelium locally stripped off) show current influx, while an accidentally denuded oocyte produced no current. Our results show that individual follicles may be electrophysiologically different, though their uniform differentiation during vitellogenesis does not reflect such heterogeneity. PMID- 3090058 TI - Intracellular electrical potential measurements in Drosophila follicles. AB - We measured the intracellular electrical potential in oocyte and nurse cells of Drosophila follicles at different developmental stages (6-14) and determined the intrafollicular potential difference. During stages 8-10B, when intrafollicular transport is known to occur, no significant potential difference was found. During late vitellogenic stages the nurse cells assume a more positive potential than the oocyte. This result contrasts with the published data on Hyalophora follicles, in which intercellular electrophoresis of negatively charged proteins occurs from nurse cells to oocyte as a result of an intrafollicular potential difference (nurse cells more negative than the oocyte). Such a potential difference was not observed in Drosophila follicles at any stage, not even after application of juvenile hormone. The extrafollicular electrical field is described with a dipole model. The hypothetical dipole is located in the long axis of the follicle and changes its calculated length stage-specifically. PMID- 3090059 TI - Elemental concentration gradients between subcellular compartments. AB - To gain information on the mechanisms involved in the establishment and maintenance of subcellular gradients of Na, K, Cl and other elements in the flagellate, Euglena gracilis, we turned to the technique of ultracentrifugal stratification of its intracellular contents, which is achieved without loss of viability or cell rupture. Stratified and non-stratified Euglena were cryofixed for energy-dispersive X-ray microanalysis of Na, K, Cl and other elements in thin freeze-dried cryosections. A number of significant elemental concentration differences (expressed as mmol kg-1 dry weight) were found between chloroplast, nucleus, paramylon granules and open cytoplasm (which contained ribosomes, membranes and macromolecules associated with the cytomatrix) in the non stratified cells. Stratification caused several ions to be redistributed. For example, we observed a significant increase in K and Cl in the nucleus, which was correlated with the condensation of chromatin. Also Cl, but not Na, decreased significantly in the region of cytoplasm that was cleared of observable ribosomes, membranes and macromolecules associated with the cytomatrix, as well as of observable cytochemical enzyme activity. We conclude from the data that more than half of the Cl in open cytoplasm was adsorbed to or entrapped in material that was removed by ultracentrifugation. Thus, it appears that a close association of at least one ion, Cl, with ultracentrifugable material is involved in maintenance of the measured Cl concentration in the open cytoplasm of the non stratified cell. PMID- 3090060 TI - Membrane fusion events in the Ca2+/ionophore-induced acrosome reaction of ram spermatozoa. AB - An acrosome reaction was induced in ejaculated ram spermatozoa by treatment with calcium and the ionophore A23187. Samples were fixed at different times after initiation of induction, and the morphological changes within the head membranes that took place as exocytosis occurred were studied in freeze-fracture replicas. Reacted acrosomes appeared in individual spermatozoa within the calcium/ionophore treated population at different times after the start of treatment; the first cells had reacted by 10 min, whereas some took more than 40 min to react. No changes were observed in control populations. An early effect of treatment (seen in most cells within 10 min) was the appearance of particle-free 'clearings' in the plasma membrane over the entire acrosomal region, with aggregation of intramembranous particles between and around these 'clearings'. At the same time, there was an increase in the number of large particles (greater than or equal to 10 nm) within the plasma membrane over the 'lunula' of the equatorial segment and the anterior part of the post-acrosomal region. Fusion of the plasma and outer acrosomal membranes began in a limited area at the border between the anterior and equatorial segments of the acrosome. It then spread, following arborescent pathways, sideways along this border and forwards towards the apex of the head. This labyrinthic propagation resulted in an 'acrosomal cap' increasingly fenestrated towards its posterior margin. Fusion propagation over the equatorial segment was inhibited, apparently as a result of the highly ordered structure of the membranes in this region. PMID- 3090061 TI - Chronic dexamethasone pretreatment aggravates ischemic neuronal necrosis. AB - This study addresses the question of whether the cyclooxygenase inhibitors indomethacin and diclofenac and the glucocorticosteroid dexamethasone ameliorate neuronal necrosis following cerebral ischemia. In addition, since these drugs inhibit the production of prostaglandins and depress phospholipase A2 activity, respectively, the importance of free fatty acids (FFAs) on the development of ischemic neuronal damage was assessed. Neuronal damage was determined in the rat brain at 1 week following 10 min of forebrain ischemia. The cyclooxygenase inhibitors, whether given before or after ischemia, failed to alter the brain damage incurred. Animals given dexamethasone were divided into three groups and the drug was administered at a constant dosage of 2 mg/kg: (a) 2 days, 1 day, and 3 h intraperitoneally before (chronic pretreatment), (b) 3 h intraperitoneally before (acute pretreatment), and (c) 5 min intravenously and 6 h and 1 day intraperitoneally after (chronic posttreatment) induction of ischemia. Acute pretreatment did not affect the histopathological outcome. Chronic posttreatment of animals with dexamethasone ameliorated the damage inflicted on the caudate nucleus, but had no effect on other brain areas investigated. Unexpectedly, the chronic pretreatment aggravated the brain damage and caused seizures following ischemia. Histopathological data showed massive neuronal damage in these brains. The accumulation of FFA levels during ischemia was markedly suppressed, and the decrease in the energy charge was curtailed by chronic pretreatment with dexamethasone. However, brain glucose levels in control animals and lactic acid concentrations following 10 min of ischemia were significantly higher both in the cerebral cortex and in the hippocampus of dexamethasone-treated animals. These results suggest that aggravation of neuronal necrosis by chronic dexamethasone pretreatment could be ascribed to lactic acidosis due to hyperglycemia in combination with an action of dexamethasone on glucocorticoid receptors in the brain. PMID- 3090062 TI - Chromosome anomalies in hematologic malignancies. PMID- 3090063 TI - Supraventricular tachycardia in chronic pulmonary disease. PMID- 3090064 TI - Immunodeficiency in chronic pediatric respiratory illness. PMID- 3090065 TI - Septic arthritis, a complex diagnostic puzzle. PMID- 3090067 TI - PHIPS for management of pulmonary edema. PMID- 3090066 TI - Sex and aging--expectations and reality. PMID- 3090068 TI - Thiamine-deficiency cardiomyopathy. PMID- 3090069 TI - Persistent jaundice and failure to thrive. PMID- 3090070 TI - Two elderly men with reversible dementia. PMID- 3090071 TI - Occupational therapy for chronic pain. PMID- 3090072 TI - Mitral valve prolapse in childhood. PMID- 3090073 TI - An apple or an orange? PMID- 3090074 TI - Dietary sodium and blood pressure. PMID- 3090075 TI - Pleural effusions and abnormal nails. PMID- 3090076 TI - Physiology of bone: mechanisms of osteopenic disorders. PMID- 3090077 TI - Foo-ta-ta-roo and all that. Some guideposts amid the decline in cardiovascular physical diagnosis. PMID- 3090078 TI - Hodgkin's disease: no stage beyond cure. PMID- 3090079 TI - Partition of purified human thyroxine-binding globulin in aqueous two-phase systems in response to reactive dyes. AB - Thyroxine-binding globulin was isolated from pooled human serum by a two-step method involving affinity chromatography on thyroxine-Sepharose and preparative disc-electrophoresis. The final product was found to be homogeneous by polyacrylamide gel electrophoresis and has a molecular weight of 59,000. Isoelectric focusing resolved the protein into seven bands with isoelectric points ranging from 3.9 to 4.3. The isolated protein showed affinity to a number of different dyes as recognized by affinity phase partitioning. The interaction of the protein with the dye Cibacron Blue F3G-A was found to be strongly competitive with the natural ligand thyroxine. PMID- 3090080 TI - Hydrophobic adsorbents for the isolation and purification of biosynthetic human growth hormone from crude fermentation mixtures. AB - Hydrophobic interaction chromatography was used as the initial step for the concentration and partial purification of biosynthetic human growth hormone (hGH). This molecule was extracted from the culture medium of a transformed monkey kidney cell line by batch adsorption either to Octyl-Sepharose or Phenyl Sepharose. The adsorbate was decanted and packed into a column for elution. This initial work-up procedure rendered a concentrated hGH solution that was further purified by ion-exchange and gel filtration chromatography. The hGH obtained was homogeneous, based on polyacrylamide gel electrophoresis, N-terminal sequence and fingerprint analysis. PMID- 3090081 TI - Capillary gas chromatographic analysis of methylsulphone metabolites of polychlorinated biphenyls retained in human tissues. AB - Structures and concentrations of methylsulphone (MSF) metabolites of polychlorinated biphenyls (PCBs) retained in the liver, lung and adipose tissue of a yusho patient and of a normal person were studied using capillary gas chromatography coupled with electron-capture detection or mass spectrometry. More than 60 isomers of tri-, tetra-, penta- and hexachloro-MSF-biphenyls were detected in the lung of the yusho patient, and the gas chromatographic peaks coincided with those of 40 authentic isomers in retention times by three separate capillary columns, when they were compared with those of 86 synthesized reference compounds. The main components of MSF-PCBs identified in the Yusho patient were 4 MSF-2,5,4'-tri-, 4-MSF-2,5,2',4'-tetra-, 4-MSF-2,5,2',5'-tetra-, 3-MSF-4,5,2',3' tetra-, 4-MSF-2,5,2',3',4'-penta- and 4-MSF-2,5,2',4',5'-pentachlorobiphenyls, estimated to be 0.7-1.5 micrograms/kg in the lung and 0.3-1.5 micrograms/kg in the adipose tissue. PMID- 3090082 TI - High-performance liquid chromatographic determination of terfenadine in commercial tablets. PMID- 3090083 TI - Rapid, simple and efficient extraction of arachidonic acid metabolites, including the sulphidopeptide leukotrienes LTC4 and LTD4, using octadecyl reversed-phase extraction columns. PMID- 3090084 TI - Rapid method for determining desmosine, isodesmosine, 5-hydroxylysine, tryptophan, lysinoalanine and the amino sugars in proteins and tissues. AB - A rapid and sensitive chromatographic method is described for determining desmosine, isodesmosine, 5-hydroxylysine, tryptophan, lysinoalanine, glucosamine and galactosamine at picomole levels in protein and tissue hydrolysates. This method uses either an automated amino acid analyser with a 17.5 X 0.28 cm microcolumn packed with 6.0 +/- 0.5 micron spherical resin, thermostated at 52 degrees C, one buffer system (0.21 M sodium citrate, pH 5.125) and 3 nitrotyrosine as the internal standard, or conventional instruments using the same system but with larger diameter columns and resins (11.0 +/- 1.0 micron). This method should be especially valuable for determining collagen and elastin in tissue hydrolysates from the amounts of 5-hydroxylysine, and desmosine or isodesmosine present, respectively, and for studying protein hydroxylation, glycosylation, cross-linking formation, and the turnover rates of collagen and elastin in normal and diseased tissues. PMID- 3090085 TI - Determination of indican and tryptophan in normal and uraemic patients by high performance liquid chromatography with a new electrochemical detector. AB - A simple analytical procedure has been developed for the determination of indican and tryptophan in biological fluids by reversed-phase liquid chromatography using a new electrochemical detector consisting of a tubular anode obtained by moulding graphitized carbon black and polyethylene. The hydrodynamic voltammetry of these compounds has been carried out and it has been found that, by operating in isocratic conditions with phosphate buffer (pH 4.0)-methanol (93:7), the reported compounds can be determined directly. The procedure can be applied for the determination of the free compounds on ultrafiltered serum as well as of their total content on serum deproteinized with methanol. Levels of both compounds in normal and uraemic patients have been measured and the relative ratios between free and total content yield a useful marker for patients with renal disease. The limits of quantitation of indican and tryptophan in serum were 5 and 10 ng/ml, respectively. The within-day assay coefficient of variation for total indican and tryptophan ranged from 3.0 to 3.6% and from 3.8 to 4.1%, respectively. The day-to day assay coefficient of variation for total indican and tryptophan ranged from 3.4 to 3.7% and from 4.6 to 5.0%, respectively. PMID- 3090086 TI - Rapid separation of arachidonic acid metabolites by silicic acid chromatography for subsequent quantitative analysis by gas chromatography-mass spectrometry. PMID- 3090087 TI - Gas chromatographic profiling of ketone bodies and organic acids in diabetes. AB - Diabetes mellitus is a defect not only in glucose metabolism, but also in the metabolism of lipids and amino acids. Gas chromatographic and gas chromatographic -mass spectrometric profile analyses have contributed much to the understanding of the metabolic changes connected with this defect. Ketones are isolated by a gas-phase extraction and adsorption technique and profiled after thermal desorption. Organic acids are isolated by solvent extraction or anion exchange, derivatized and separated either as total acid profiles or subprofiles after pre fractionation of the acid derivatives. The main results are as follows. (a) Increased total 4-heptanone is inherently connected with diabetes mellitus. Its urinary levels are elevated in therapeutically well controlled patients. (b) A general ketogenesis pathway leads to higher molecular weight ketone bodies in addition to the conventional ketone bodies. (c) During diabetic ketoacidosis, in addition to the fatty acids the following acids are elevated in serum and in urine: dicarboxylic acids resulting from omega- and beta-oxidation of monocarboxylic acids; oxomonocarboxylic acids as metabolites of the amino acids valine, leucine and isoleucine and as products of ketogenesis; and hydroxymonocarboxylic acids, also originating from amino acids and from ketogenesis. PMID- 3090089 TI - The influence of uninterpretability on the assessment of diagnostic tests. AB - A frequent problem faced by physicians utilizing diagnostic tests is the occurrence of uninterpretable test results. Such results, if they occur commonly, can seriously impair the diagnostic performance of the test. Moreover, in assessing the characteristics of the test, i.e. sensitivity, specificity, etc. failure to consider the impact of uninterpretability will artificially inflate the test characteristics. In this paper we explore the implications of this issue. We observe that a relevant factor is the potential repeatability of the test, i.e. whether the cause of uninterpretability is a transient phenomenon or an inherent property of the subject. We distinguish uninterpretable results, in which no result is obtained, from indeterminate results, in which the result is equivocal, or for which predisposing concomitant factors limit the interpretability of the result. Our results demonstrate that the naive approach of ignoring uninterpretable results in test assessments may indeed be unbiased in certain circumstances. However, if the cause of uninterpretability is related to disease status or to the potentially observable test result, then this approach will lead to bias. In either case, the frequency of uninterpretability is an important consideration in the cost-effectiveness of the test. PMID- 3090088 TI - Immunocytochemical methods for demonstrating canine distemper virus antigen in aldehyde-fixed paraffin-embedded tissue. AB - The effects of enzymatic digestion, sodium borohydride reduction, acids used in decalcification procedures and techniques for inactivation of endogenous peroxidase were sequentially evaluated for their effect on the immunoreactivity of canine distemper virus in aldehyde-fixed paraffin-embedded tissue. Enzyme digestion improved immunoreactivity while sodium borohydride reduced background staining. Paraformaldehyde-glutaraldehyde-fixed tissues required thioglycolic acid treatment prior to enzyme digestion and sodium borohydride reduction to obtain results comparable to results obtained in formalin-fixed tissues. Detailed protocols for indirect immunofluorescence and the avidin-biotin-peroxidase complex procedure are provided. PMID- 3090090 TI - Syncope in institutionalized elderly: the impact of multiple pathological conditions and situational stress. AB - We conducted a prospective study to identify clinical factors which predispose institutionalized elderly to syncope. Over 3 years, 97 patients (mean age = 87 +/ 6 y) developed syncope. On clinical evaluation, diagnoses fell into two categories: specific diseases including myocardial infarction (6%) and aortic stenosis (5%); and situational stresses including drug-induced hypotension (11%), postprandial syncope (8%), defecation syncope (7%) and postural hypotension (6%). Clinical variables derived from the history, physical examination, and laboratory evaluation of these patients were compared to those of 118 non-syncopal age matched subjects evaluated in similar fashion. Multivariate analysis identified five independent statistically significant correlates of syncope: coronary artery disease (p = 0.0003), functional impairment (p = 0.006), postural blood pressure reduction (p = 0.003), aortic stenosis (p = 0.008), and insulin therapy (p = 0.03). Syncope patients were more likely than controls to have two or more coexistent factors (p = 0.0001). Syncope in institutionalized elderly is often due to the interaction of multiple coexistent clinical abnormalities which impair cardiovascular compensation for common situational stresses. PMID- 3090091 TI - Goiter size and thyroid function in an endemic goiter area in northern Italy. AB - Thyroid function was studied in a large number of subjects residing in Varsi, a town in the province of Parma, Italy. In this area, endemic goiter associated with moderate iodine deficiency [59 +/- 3 (+/- SE) microgram iodine/g creatinine], as defined by WHO criteria, affects 65% of the population. Serum T4, T3, thyroglobulin (Tg), and TSH concentrations were measured by RIA in 1218 subjects. The TSH response to TRH was determined in 108 subjects selected randomly from the groups with different grades of goiter. No significant change in serum T4 concentrations was found in subjects with different grades of goiter. Serum T3 concentrations were higher in subjects with the larger goiters. Serum Tg concentration progressively increased, and serum TSH progressively decreased with increasing goiter size. The TSH response to TRH was diminished in subjects with larger goiters. The findings of decreasing serum TSH concentrations and blunted TSH responses to TRH as goiter size increased suggest the possibility of autonomous thyroid function in the larger goiters in subjects residing in this area of moderate iodine deficiency. PMID- 3090093 TI - Relationship of plasma growth hormone-releasing hormone levels to pubertal changes. AB - Basal plasma GH-releasing hormone (GHRH) concentrations were measured by RIA in 180 normal subjects (93 boys and 87 girls between the ages of 8 and 18 yr). Every subject was in good health and between -2 and +2 SD for height. Fourteen boys with delayed puberty also were studied. Plasma GHRH concentrations were higher during puberty than before it. At midpuberty, the mean GHRH levels in girls was 159.1 +/- 28.5 (+/- SEM) pg/ml, approximately 5-fold higher than the level in prepubertal girls (30.3 +/- 4.3 pg/ml). The mean plasma GHRH in midpubertal boys (101.4 +/- 11.5 pg/ml) was approximately 2-fold higher than the level in prepubertal boys (48.1 +/- 5.2 pg/ml). The GHRH levels in boys with delayed puberty more closely resembled those in boys at a similar pubertal stage than those in boys of similar chronological age. The dramatic rise in plasma GHRH levels during puberty suggests a role for this peptide in the adolescent growth spurt. Moreover, these data indicate that GHRH levels during adolescence may be a marker of the patient's pubertal development. PMID- 3090092 TI - Toward removing uterine fibroids without surgery: subcutaneous infusion of a luteinizing hormone-releasing hormone agonist commencing in the luteal phase. AB - Intermittent sc injection of a LHRH agonist reduced uterine fibroid size in 5 women. Commencement of the LHRH agonist buserelin on day 21 of the menstrual cycle induced a marked increase in plasma LH and FSH concentrations, followed by rises in estradiol (E2) and progesterone. LH and FSH levels fell to within the normal range by 120 h after beginning buserelin, despite continuing administration of the agonist. After menstruation, marked sustained suppression of cyclical gonadotropin and steroid concentrations occurred: mean values of FSH, LH, and E2 were 4.9 +/- 0.5 (+/- SE) mIU/ml, 5.9 +/- 0.6 mIU/ml, and 47.9 +/- 10.8 pg/ml, respectively, during the 20 weeks of buserelin treatment. During treatment, E2 concentrations remained below 50 pg/ml in 98 of 116 weekly observations. Uterine fibroids shrank after 8 or 10 weeks of buserelin administration, as assessed by ultrasound or gynecological examination. Compared to their initial volume, mean uterine fibroid volume after 20 weeks of buserelin infusion decreased from 220 +/- 51 to 98 +/- 26 cm3, which was 39.4 +/- 6.9% of the pretreatment volume. We conclude that sc administration of a LHRH agonist beginning in the luteal phase markedly reduced the size of uterine leiomyomata, suppressed, but did not abolish, pituitary and ovarian function, and warrants further evaluation as an option or adjunctive therapy to uterine myomectomy or hysterectomy. PMID- 3090094 TI - Thyrocyte HLA-DR expression and interferon-gamma production in autoimmune thyroid disease. AB - We examined the expression of HLA-DR antigen induced by mitogen, mitogen-free supernatants from mitogen-stimulated peripheral blood mononuclear cells (PBMC), or autologous and allogeneic PBMC on thyrocytes cultured for 1-2 weeks (precultured) before the addition of the stimulant. Leucoagglutinin (LAG) and concanavalin A, but not lipopolysaccharide induced HLA-DR expression on thyrocytes from normal subjects (NC) and patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT). The degree of DR expression induced by LAG was significantly less in GD than in NC thyrocytes. This response was dependent on contaminating T cells, especially suppressor-cytotoxic T (Ts/c) cells, NK cells, and HLA-DR+ cells, but not helper-inducer T (Th/i) cells or B cells, in the thyrocyte cultures. OKT3 monoclonal antibody, which activates T cells specifically in the presence of monocytes, also induced thyrocyte HLA-DR expression. Furthermore, interferon-gamma (IFN-gamma) was detected in culture supernatants from LAG-stimulated thyrocytes. Anti-IFN-gamma monoclonal antibody eliminated the ability of LAG to induce HLA-DR. Mitogen-free supernatants from mitogen-stimulated PBMC also induced thyrocyte HLA-DR expression, which was inhibited by anti-IFN-gamma. The supernatants of concanavalin A- or LAG stimulated PBMC from either untreated or recently treated patients with GD or hypothyroid HT induced less thyrocyte DR expression than NC PBMC. Indeed, the levels of IFN-gamma in supernatants from such patients were lower than those in NC, and the correlation between DR expression and IFN-gamma levels was significant. This IFN-gamma production by PBMC required Th/i cells, NK cells, and HLA-DR+ cells. Before the addition of autologous or allogeneic PBMC, only precultured HT thyrocytes expressed HLA-DR, whereas GD and NC thyrocytes did not. The induction or enhancement of DR expression on autologous thyrocytes by direct coculture with PBMC occurred within 8 days in GD and HT, but not in NC. There was a significant correlation between the serum titer of antithyroid microsomal antibodies and the degree of DR expression. Allogeneic normal PBMC also induced DR expression on NC and GD thyrocytes within 8 days, the effect on the latter being more pronounced than with autologous GD PBMC. Thyrocyte HLA-DR expression induced by autologous GD PBMC and allogeneic normal PBMC required monocytes. Th/i, and NK cells and was blocked by anti-IFN-gamma. However, the enhancement of thyrocyte DR expression by autologous HT PBMC did not require monocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3090095 TI - An analysis of plasma estradiol concentrations during clomiphene citrate-human menopausal gonadotropin stimulation in an in vitro fertilization-embryo transfer program. AB - We report here a range of plasma estradiol (E2) concentrations suitable for use in an in vitro fertilization (IVF) program. This range was derived from nonparametric analysis of plasma E2 levels using plasma E2 measurements beginning 10 days before the anticipated day of the midcycle LH surge (midpoint), as calculated from each patient's six previous menstrual cycles, during which time the patients all received the same ovarian stimulation regimen. The regimen consisted of 100 mg clomiphene citrate/day for 5 days, beginning 10 days before the anticipated midpoint, plus 150 IU human menopausal gonadotropin, commencing the day after clomiphene. A consecutive series of 102 IVF conception cycles induced in this standardized fashion were analyzed in this study. The 5th-95 percentile envelope of plasma E2 concentrations was derived as a valid clinical indicator of satisfactory folliculogenesis during IVF treatment. Five women had plasma E2 concentrations below the 5th percentile of the E2 range on at least 3 consecutive days of ovarian stimulation, while six women had E2 levels above the 95th percentile of this range on at least 3 consecutive days. This plasma E2 range defined objectively the diagnoses of ovarian hyperstimulation and inadequate stimulation in an IVF program. These criteria should help clinicians in managing ovarian responses during IVF superovulation stimulation treatment. PMID- 3090096 TI - The role of thyroxine (T4)-binding serum proteins in oleic acid-induced increase in free T4 in nonthyroidal illnesses. AB - We studied the effects of various concentrations of oleic acid (0.1-3.3 mM), such as are often found in the serum of patients with nonthyroidal illness, on the dialyzable (free) fraction of T4 (DFT4) in three types of serum samples: pooled normal serum (PNS), pooled pregnancy serum (PPS), and pooled serum of hospitalized patients (PSHP). The samples were extracted with diethyl ether to remove endogenous fatty acids before being tested in the DFT4 assay. Oleic acid caused only a moderate increase in DFT4 in PNS; a significant (greater than 2 SD above control) increase (15%) was found with 2.0 mM oleic acid, and the maximal dose of oleic acid (3.3 mM) caused a 33% increase in DFT4. However, the DFT4 increasing effect of oleic acid was enhanced (increase in DFT4 of 33% caused by 0.9-1.2 mM oleic acid) when the serum tested had low (0.5 times normal) albumin and prealbumin concentrations with either normal (50% PPS) or half-normal TBG (50% PNS). The effect of oleic acid in 100% PSHP was significantly (P less than 0.005) greater than that in 100% PNS, and it was close to that in 50% PNS (increase in DFT4 with 3.3 mM oleic acid, 118% in PSHP vs. 98% in 50% PNS). Normalization of serum albumin in PSHP by adding exogenous albumin markedly reduced the DFT4-increasing effect of oleic acid; the maximal increase in DFT4 of 64% with 3.3 mM oleic acid in albumin-normalized PSHP was equalled with 1.3 mM oleic acid in unmodified PSHP. The data suggest that the serum concentrations of albumin and other T4-binding proteins are important in modulating the DFT4 increasing effect of oleic acid and that oleic acid may contribute to the reduced serum binding of T4 in nonthyroidal illness. PMID- 3090097 TI - The changing ratio of serum bioactive to immunoreactive follicle-stimulating hormone in normal men following treatment with a potent gonadotropin releasing hormone antagonist. AB - Using a recently developed granulosa cell aromatase bioassay (GAB), we measured serum bioactive follicle-stimulating hormone (bio-FSH) levels in 5 normal men after administration of a potent GnRH antagonist. Although only minimal suppression of immunoreactive FSH (immuno-FSH) was detected during administration of 20 mg of the antagonist, [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-h(Arg(Et2)6,D Ala10]GnRH , pronounced inhibition (79 to 89%) of bio-FSH levels occurred. Concomitantly, the ratio of bio- to immuno-FSH levels dramatically decreased within 6 h after antagonist administration. These data reinforce earlier expectations that GnRH antagonists might be potential male contraceptives and provide the first report of changes in circulating bio- to immuno-FSH levels. The GAB assay will facilitate future studies on the biochemical mechanisms by which GnRH antagonists induce changes in the bioactivity of circulating FSH. PMID- 3090098 TI - Mechanical stimulation activates beating in calcium-arrested lateral cilia of Mytilus edulis gill. AB - Lateral cilia of Mytilus edulis gill arrest upon mechanical stimulation, the result of calcium influx. A mechanical stimulus that deflects these cilia toward the effective stroke, and is normally sufficient to cause transient arrest in beating lateral cilia or transient movement into the recovery stroke in quiescent cilia, initiates beating in Ca2+ ionophore-arrested cilia at 9-15 Hz, for periods as long as 30 s. This movement is restricted to the stimulated cilia and the beat pattern appears constrained in the first half of the beat cycle. Application of dopamine causes ciliary arrest in the presence (but not absence) of Ca2+ and mechanical stimulation will also activate such cilia to beat. In the presence of ATP, mechanical stimulation of detergent-permeabilized lateral cell models arrested in the presence of 50 microM Ca2+ will also cause activation comparable in frequency, duration, and beat pattern to that seen in Ca2+-arrested cells, but the initiation is more difficult. Upon application of ionophore in Ca2+-free (EGTA) seawater, the cilia become quiescent, stopped at the end of the recovery stroke. Mechanical stimulation will cause activation of beat, with a similar range of frequencies and duration as in Ca2+-arrested lateral cilia, but the beat pattern is normal and cilia of adjacent cells may also beat, presumably initiated by mechanical coupling. Gently lifting cilia at their basal ends, using small, slow movements of a mechanical probe, will initiate several beat cycles in quiescent lateral cilia but will cause Ca2+-arrested cilia to 'snap' into the effective stroke and back.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090099 TI - Effects of carbon dioxide and tetanus duration on relaxation of frog skeletal muscle. AB - Sartorius and semitendinosus muscles of the frog Rana temporaria (0 degrees C) were stimulated under isometric (fixed-end) conditions and force during stimulation and relaxation was recorded. Relaxation time was assessed by measuring the time from the last stimulus until force declined to 90% or 50% of its value at that time. The relaxation time increased linearly with concentration of CO2 in the Ringer's solution (pH 7.2), whereas, at constant CO2, relaxation was hardly affected by changes in extracellular HCO3- and pH. This is consistent with the view that CO2 enters the cells, but H+ and HCO3- do not, and that entry of CO2 causes intracellular acidification and slows relaxation. For tetani lasting between 0.5 and 5s, relaxation is slower the longer the tetanus; further increase in tetanus duration to 10 s has little additional effect. The presence of 3.3 mmol 1(-1) CO2 in the Ringer's solution has a small effect on relaxation after a brief tetanus, but greatly slows relaxation as tetanus duration increases. Experiments with paired tetani (conditioning and test) showed that relaxation from a test tetanus was slower if a conditioning tetanus was given. However, the size of this effect was independent of muscle length during the conditioning tetanus. After a conditioning tetanus, an interval of many minutes is required for the muscle to recover its ability to relax quickly from a test tetanus. The results indicate that changes in metabolite levels caused by contraction itself are not responsible for the slowing of relaxation. Possible mechanisms of the effects of CO2 on relaxation are discussed. PMID- 3090101 TI - Cost containment through payment mechanisms: the Quebec experience. PMID- 3090100 TI - Immunogenetic markers in chlorpromazine-induced tardive dyskinesia. AB - The presence and severity of tardive dyskinesia were determined in 66 patients with chronic psychiatric disorders treated with chlorpromazine. The patients were classified according to the presence of antinuclear antibodies, the lupus anticoagulant, and the HLA antigen Bw44. The severity of orofacial dyskinesia was estimated using the Rockland Research Institute Scale. Patients with autoantibodies and the Bw44 antigen had higher tardive dyskinesia scores than those with AAB without the Bw44 antigen and also patients without autoantibodies regardless of their HLA phenotype (P less than 0.01). These studies suggest that the presence of autoantibodies in association with the HLA Bw44 antigen is related to, and can be a predictor of, neurological complications of long-term chlorpromazine therapy. PMID- 3090102 TI - Correlation of the Km(1) immunoglobulin allotype with anti-polysaccharide antibodies in Caucasian adults. AB - Km allotype antigens are serologic markers expressed on kappa light chains of human immunoglobulins. To determine whether th Km phenotype of an individual is related to his ability to make antibodies to polysaccharide antigens, we correlated the Km allotypes of 129 healthy caucasian adults with the concentrations of specific antibodies to three bacterial polysaccharide antigens after immunization. The 14 individuals expressing the Km(1) allotype had lower concentrations of IgG, IgM, and IgA antibodies by enzyme-linked immunosorbent assay and total antibody by radioimmunoassay to Haemophilus influenzae type b and Neisseria meningitidis group C capsular polysaccharides when compared with the 115 Km(1) negative individuals. The Km-associated differences in H. influenzae type b and N. meningitidis group C antibody concentrations were confined to kappa light chain-containing antibody (P = 0.029 and 0.003, respectively). Similarly, the Km(1) positives had slightly lower kappa chain-containing Ig than the Km(1) negatives (P = 0.079). We conclude that genes in or near the kappa light chain locus play a role in the regulation of kappa-containing antibody production to some bacterial polysaccharides and perhaps to other antigens. PMID- 3090103 TI - In vitro hepatitis B virus infection of human bone marrow cells. AB - Infection of humans with hepatitis B virus (HBV) frequently results in suppression of hematopoiesis; in some cases this may lead to severe bone marrow failure. The mechanism whereby HBV infection affects hematopoiesis is unknown. In vitro exposure of human bone marrow to HBV results in a dose-dependent inhibition of erythroid (erythroid burst forming units, BFU-E; erythroid colony-forming units CFU-E), myeloid (colony-forming units-granulocyte macrophage CFU-GM), and lymphoid (CFU-[T-lymphocytic]-TL) hematopoietic stem cells. Inactivation or immunoabsorption of HBV from sera resulted in loss of HBV-induced inhibition of hematopoietic stem cells. De novo gamma interferon was not detectable in the supernatants of cultures of bone marrow cells with HBV. Antibodies to gamma interferon did not affect the suppression of hematopoietic stem cells by HBV. Hepatitis B surface antigen (HBsAg) was detected by immune electron microscopy in nuclei of greater than 70% of immature hematopoietic cells including myeloblasts, normoblasts, and lymphoblasts; granulocytes had mostly cytoplasmic HBsAg. Hepatitis B virus core antigen (HBcAg) was also detected in about 5% of HBV infected bone marrow cells by immunoperoxidase staining. These data indicate that HBV can infect hematopoietic cells and their progenitors, thus suggesting a wider range of tropism for HBV than previously reported. These results may provide a basis to study HBV infection in vitro, and the effects of HBV on hematopoiesis. PMID- 3090104 TI - Enhancement of mononuclear procoagulant activity by platelet 12 hydroxyeicosatetraenoic acid. AB - Platelets induce generation of procoagulant tissue factor activity (TFa) by mononuclear leukocytes, and also enhance the TFa induced by endotoxin. Our present investigation demonstrated that arachidonic acid, which by itself had no effect on mononuclear TFa, greatly enhanced platelet-induced TFa. The effect was concentration dependent for both platelets and arachidonate (1-20 microM); other fatty acids tested were inactive. The enhancing effect of arachidonate was more pronounced if platelets were exposed to aspirin, suggesting lipoxygenase product involvement. Production of 12-hydroxyeicosatetraenoic acid (12-HETE) was demonstrated biochemically in aspirin-treated platelet/arachidonate/mononuclear cell preparations that generated high levels of TFa. The enhancing role of 12 HETE was verified as follows. Addition of platelet-derived or synthetic 12-HETE amplified endotoxin-induced TFa more than threefold. Other lipoxygenase products were inactive. Enhancement of mononuclear cell TFa by 12-HETE represents a newly described biological function for this eicosanoid in cell-cell interactions between platelets and mononuclear cells. PMID- 3090105 TI - Regulation of the fibrinolytic system of cultured human vascular endothelium by interleukin 1. AB - We examined the effects of human interleukin 1 (IL-1) on the production of fibrinolytic components by cultured human vascular endothelium. Conditioned media collected from IL-1-treated (5 U/ml, 24 h) monolayers exhibited decreased tissue type plasminogen activator (tPA) activity and increased plasminogen activator inhibitor (PAI) activity, as assessed by fibrin and reverse fibrin-autography. Quantitative immunological assays revealed a 35% decrease in tPA antigen and a 360% increase in active PAI antigen, after incubation for 24 h with 0.6 U/ml IL 1. Maximal effects (approximately 50% decrease in tPA antigen; 400-800% increase in active PAI antigen) were observed with 2.5-5 U/ml IL-1. Changes in tPA and PAI reached a maximum at approximately 24 h and persisted for greater than 48 h. IL-1 induction of endothelial procoagulant activity was more rapid and transient, peaking by 6 h and subsiding by 24 h. Natural monocyte-derived IL-1 and two species of recombinant IL-1 had comparable effects. Heat and polymyxin-B treatments differentiated IL-1 actions from those of endotoxin, which promoted similar endothelial alterations. IL-1 effects on endothelial procoagulant and fibrinolytic activities may contribute to the generation and maintenance of fibrin in pathophysiological settings in vivo. PMID- 3090106 TI - Human recombinant granulocyte-macrophage colony-stimulating factor increases cell to-cell adhesion and surface expression of adhesion-promoting surface glycoproteins on mature granulocytes. AB - Human granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to inhibit migration of mature granulocytes and to enhance their antibody-dependent cellular cytotoxicity. We found that human recombinant GM-CSF also enhanced granulocyte-granulocyte adhesion and increased by two- to threefold the surface expression of Mo1 and LeuM5 (P150, 95), two members of a family of leukocyte adhesion molecules (Leu-CAM). Increased Mo1 surface expression occurred within 15 min at 37 degrees C and was maximal at the migration inhibitory concentration of 500 pM. One-half maximal rise in the expression of Mo1 on the cell surface occurred at 5 pM. The chemotactic peptide f-Met-Leu-Phe produced a comparable rise in surface Mo1 with one-half maximal expression occurring at 7 nM. Both GM CSF and f-Met-Leu-Phe produced optimal granulocyte-granulocyte adhesion at 500 pM and 100 nM, respectively. This adhesion-promoting effect induced by either stimulus was inhibited by a mouse monoclonal antibody directed against Mo1 antigen. These data indicate that GM-CSF promotes cell-to-cell adhesion, presumably through enhanced expression of leukocyte adhesion molecules. This mechanism may explain, in part, the known effects of GM-CSF on the function of mature granulocytes. PMID- 3090107 TI - Effects of hyperglycaemia and sorbitol accumulation on erythrocyte deformability in diabetes mellitus. AB - Erythrocyte deformability was studied in a total of 83 poorly controlled diabetics (mean blood glucose 12.2 mmol/l) who were divided into three groups, each with matched healthy controls. There was no appreciable difference between diabetics and matched controls regarding the filtration of erythrocytes through 3 micron diameter straight channel pores (25 diabetics) or tortuous channel pores (28 diabetics), or for the measurement of erythrocyte elongation over a range of osmolalities in the Ektacytometer (30 diabetics). When erythrocytes from 17 additional diabetics and 17 healthy controls were incubated for two hours at 37 degrees C in hyperglycaemic (50 mmol glucose/l) buffer, however, there was a considerable reduction in erythrocyte filterability for both diabetics and controls in parallel with an increase in erythrocyte sorbitol concentration. This loss of filterability was prevented by the addition of an aldose reductase inhibitor (Sorbinil). High glucose concentrations (congruent to 50 mmol/l) impair the filterability of erythrocytes through 3 micron pores, and the intracellular accumulation of sorbitol in poorly controlled outpatients is therefore unlikely to have a major adverse effect on erythrocyte rheology in diabetes mellitus. PMID- 3090108 TI - Distribution of immunoglobulin heavy chains in diseased synovia. AB - Synovium from 142 patients with 12 different arthropathies was examined for the distribution of alpha, delta, gamma, and mu immunoglobulin heavy chains. A high proportion of plasma cells in the superficial subintima in all diseases reacted for alpha heavy chains. Only in rheumatoid disease did the synovium contain more than 10% of plasma cells reacting for mu heavy chains. PMID- 3090110 TI - Inflammatory pseudotumour of the liver. AB - Five cases of inflammatory pseudotumour of the liver are reported and compared with seven individual previously published case reports. Clinical presentation was variable but often comprised low grade intermittent fever, vague abdominal symptoms, and a history of weight loss. Leucocytosis, raised erythrocyte sedimentation rate, and polyclonal hyperglobulinaemia were also sometimes detected. All five cases in the present series were considered to be clinically malignant; and in two the histological diagnosis was also that of malignancy. The lesion is clearly inflammatory and reactive, but the aetiology remains unknown. PMID- 3090109 TI - Histogenesis of Kaposi's sarcoma in patients with and without acquired immune deficiency syndrome (AIDS). AB - Immunohistochemical studies were performed in thirty skin biopsies from patients with Kaposi's sarcoma, who did and did not have the acquired immune deficiency syndrome (AIDS). Tumour histogenesis was rigorously tested using a battery of endothelial cell markers, which included two new monoclonal antibodies, EN4 and PAL E. These are both specific for endothelial cells and can be visualised in appropriately fixed paraffin embedded tissue. Whereas EN4 labels all endothelial cells, PAL E is negative in endothelium of lymphatic derivation. Lectin binding with Ulex europaeus agglutinin 1 (UEA-1) and the presence of factor VIII related antigen (FVIIIRA) and laminin were also examined. In nodular lesions of Kaposi's sarcoma the spindle cell areas were positive with EN4 and UEA-1, negative with PAL E, and showed focal staining for FVIIIRA and laminin. These results confirm that the tumour is of endothelial cell origin. Six patch stage lesions showed a network of angulated spaces, lined by cells that were positive with EN4 and UEA 1, negative with PAL E and anti-FVIIIRA, and showed only weak staining for laminin. This pattern was observed in both AIDS and non-AIDS related cases and strongly favours a lymphatic derivation for the tumour. This has important implications as it suggests that lymphatic endothelium may have special characteristics that lead to neoplastic transformation in patients with retrovirus infection. PMID- 3090111 TI - Pharmacokinetic drug interactions. AB - Drugs labeled with stable isotopes have been successfully used in pharmacokinetic drug interaction studies. This technique provides precise information on the mechanisms responsible for drug interactions, e.g., changes in clearance due to induction or inhibition of drug metabolism, bioavailability, and volume of distribution. It offers the advantage that detailed studies on the pharmacokinetics and metabolism of a drug can be conducted in a clinical setting during steady-state conditions, thus avoiding problems in patient management that can arise from studies in which drug is withdrawn. PMID- 3090112 TI - Evaluation of phagocytic function in Mycobacterium lepraemurium infection. AB - Infection of mice with Mycobacterium lepraemurium caused significant functional alterations of the mononuclear phagocyte system. Accelerated clearance of sheep red blood cells was consistently demonstrated throughout the infection and the infected mice showed progressive anaemia. Infected mice showed an enhanced ability to limit growth of phagocytosed Listeria monocytogenes in spleens during the early stages of infection, whereas moribund leprous mice lost this ability. Autoradiography showed that uninfected Kupffer cells and splenic macrophages of moribund mice could still phagocytose Listeria, suggesting that MLM infection did not affect the capacity of Listeria to localize to macrophages but interfered in some way with subsequent killing of such bacteria. The possible mechanisms underlying these observations are discussed. PMID- 3090113 TI - Subcutaneous fat necrosis in an infant, occurring after hypothermic cardiac surgery. Case report and analysis of etiologic factors. AB - A female infant developed extensive subcutaneous fat necrosis 3 weeks following induced hypothermia used as an adjuvant in cardiac surgery. All lesions resolved without sequelae within 4 months. In this article we discuss the various causes of panniculitis in infants and the relevance of each cause to our patient. We believe that an underlying defect in composition and metabolism of fat, coupled with a variety of exogenous and endogenous stresses, can precipitate subcutaneous fat necrosis in infants. These stresses include physical trauma (e.g., hypothermia), poor nutrition, infection, and metabolic abnormalities. PMID- 3090114 TI - Octopamine potentiates intracellular Na+ and Cl- reductions during cell volume regulation in Limulus exposed to hypoosmotic stress. AB - The biogenic amine octopamine (OCT) appears to be involved in cell volume regulation in the horseshoe crab, Limulus polyphemus, during hypoosmotic stress. OCT is present in relatively large amounts (160 nmoles/g dry wt) in the cardiac ganglion. Furthermore, OCT is released from the isolated ganglion during exposure to hypoosmotic media. This release is reflected in the elevation of blood OCT concentrations from basal levels of 4 X 10(-9) M reaching 1.2 X 10(-8) M within 72 h of exposure of animals to hypoosmotic media. The circulating OCT potentiates the hypoosmotically-induced reductions of intracellular Na+ and Cl- by a ouabain sensitive mechanism which complements the main ion regulating (ouabain insensitive) mechanisms utilized during cell volume recovery. PMID- 3090116 TI - Needs assessment in continuing education: designing a system that works. PMID- 3090117 TI - Reduction in nurses' death anxiety following a death awareness workshop. PMID- 3090115 TI - Gastric diverticulum mimicking adrenal mass: CT demonstration. PMID- 3090118 TI - Continuing education in oncology nursing. PMID- 3090119 TI - Transfer orientation: developing a retraining program. PMID- 3090120 TI - Program evaluation: as the program director sees it; as the evaluator sees it. PMID- 3090122 TI - Computer ease: continuing nursing education in computer technology. PMID- 3090121 TI - Notes on continuing education: office nurses have continuing education needs too. PMID- 3090123 TI - Ethics in continuing education. PMID- 3090124 TI - Teaching tips. Aromatics--another way to learn? PMID- 3090125 TI - [Inhibition of anaphylaxis and tumor growth]. PMID- 3090126 TI - Diarrhoea in the critically ill. PMID- 3090127 TI - The importance of the balloon reservoir volume of a CPAP system in reducing the work of breathing. AB - We have previously reported, that the work of breathing in spontaneously breathing patients on CPAP could be significantly reduced by increasing the volume of the balloon reservoir in the circuit of a CPAP system from 3 to 23 l. We now report a study designed to determine the optimum balloon reservoir volume for the minimization of the work of breathing. Twenty intubated, spontaneously breathing patients were connected to a CPAP system with interchangeable balloon reservoirs. In each patient the work of breathing was measured for reservoir volumes of 3, 6, 12, 18, and 24 l attached in random order, while the positive airway pressure was held constant at 10 cm H2O. The balloons were constructed of the same material and had similar compliance. Rebreathing was prevented with use of one-way valves. Significant (p less than 0.001) decreases in the work of breathing were found on increasing reservoir volumes from 3 to 6, 6 to 12, and 12 to 18 l. A less significant (p less than 0.01) decrease in the work of breathing was found between reservoirs of 18 and 24 l. Rebreathing did not occur with significantly (p less than 0.001) lower flow rates when large reservoirs were used. We conclude that a balloon reservoir of 18 l represents the best compromise between reduction in the work of breathing, utilization of low source flow, and convenience of clinical use. PMID- 3090128 TI - Net income. So, how much do dentists earn? Statistics are confusing. PMID- 3090129 TI - Selenium status of malnourished hospitalized patients. AB - We evaluated selenium (Se) status of 44 hospitalized patients with protein-energy malnutrition. The patients were assigned to "normal" or "low" Se groups-1 and 2, respectively-based on whether the plasma Se level exceeded or was below the value of the mean-2SD of healthy Georgians'. Plasma and erythrocyte Se levels correlated significantly (r = .52, P less than .01). Erythrocyte glutathione peroxidase activity was highly correlated with plasma Se (r = .68) in group 2; there was no significant correlation between these parameters in group 1. In group 2 the mean plasma prealbumin level was significantly lower, and the mean corpuscular volume and serum glutamic oxaloacetic transaminase level were significantly higher compared to group 1. Other nutritional parameters did not correlate with Se status. Concomitant deficiencies of other nutrients were common in both patient groups. Se levels may relate to protein status, and abnormal hematologic and hepatic parameters may reflect low Se status and/or protein energy malnutrition. Low Se status is common in malnourished patients from a low Se area, and Se supplementation should be included in their nutritional-repletion regimens. PMID- 3090131 TI - Stopped flow mass spectrometry: applications to the carbonic anhydrase reaction. AB - Membrane inlet mass spectrometry is combined with a stopped flow technique in order to allow the recording of moderately fast transients in concentrations of dissolved gases. The method was used for direct measurements of CO2 transients in the spontaneous and enzyme catalyzed hydrations of carbon dioxide. Rate constants and activation energies were determined. PMID- 3090130 TI - The effect of the digestion products of lactose (glucose and galactose) on its intraintestinal, in vivo hydrolysis by exogenous microbial beta-D-galactosidase. AB - Exogenous, microbial beta-D-galactosidases are capable of effecting hydrolysis of lactose in situ in the gastrointestinal tract of lactase-deficient subjects when given as replacement therapy at mealtime. As its digestion products-glucose and galactose-are known to inhibit lactose hydrolysis in vitro, the effect of adding excess monosaccharide to milk on the hydrolytic efficiency of a beta galactosidase from Aspergillus niger in adult lactose-malabsorbers was tested. Subjects were studied with 360-ml volumes of milk containing 18 g of carbohydrate. This was administered as intact milk, as lactose-prehydrolyzed milk, and as milk to which 399 mg of Lactase N was added within 5 minutes of consumption. This latter Lactase N-treated milk was administered alone and with graded levels of glucose-9, 18, and 36 g-and with similar doses of galactose. The Lactase N enzyme alone at mealtime reduced breath H2 production by 68% as compared to intact milk. The addition of monosaccharides produced no change in the apparent hydrolytic efficiency of the Lactase N in situ. Thus, product inhibition is unlikely to be the basis for the limited efficiency of intraintestinal hydrolysis of milk lactose by the enzyme from A niger. PMID- 3090132 TI - [Technics of the use of CO2 laser in microsurgery of sterility. Experimental study. Clinical results]. AB - The authors describe their experience in the use of CO2 laser in microsurgical treatment of tubal sterility. An experimental study was carried out on Fallopian tubes in order to define the parameters for the use of CO2 laser in tubal surgery. Certain microsurgical techniques were altered when CO2 laser was used. The procedures were improved by the ease of surgery and the speed with which it could be carried out. Our clinical experience was on 153 patients who were operated on. In 66 laparotomies the combined use of microscope and CO2 laser seemed to improve the handling of tubal sterility. PMID- 3090133 TI - Limitations in the use of 14C-glycocholate breath and stool bile acid determinations in patients with chronic diarrhea. AB - Analysis of a modified 14C-glycocholate breath test on 165 consecutive in patients being investigated for chronic diarrhea showed that the measurement of 14CO2 between 3 and 6 h after oral dosing of 5 microCi of 14C-glycocholic acid was of only limited use to distinguish between patients with Crohn's disease (CD), idiopathic bile salt wastage (IBW), or ileal resection (IR) from those with the irritable bowel syndrome (IBS). Continuing 14CO2 collections for up to 24 h was of little more help in establishing the presence of bacterial overgrowth syndrome (BOS) and in distinguishing between BOS and CD. Stool bile acid measurements were of use in differentiating between IBW and IBS, but did not distinguish between CD and BOS or between CD and IR. Since the range of normal values was defined by measurements in the IBS group, a positive test was specific for an organic cause of chronic diarrhea. Even so, the sensitivity of the test was relatively low: CD, 53%; IR, 23%; IBW, 14%; and BOS, 10%. We believe that the 24-h 14C-glycocholic breath test combined with the measurement of stool bile acids represents a screening test of only limited use for the identification of organic causes of chronic diarrhea. PMID- 3090134 TI - Clinical relevance of gastroduodenal dysfunction in reflux esophagitis. AB - This review critically evaluates the gastroduodenal factors that may play a clinically relevant role in the pathogenesis of reflux esophagitis. The gastroesophageal pressure gradient is of obvious importance, but the role of gastric contraction/relaxation is poorly understood. The intragastric volume, as well as the factors that influence it, could theoretically play a role in gastroesophageal reflux (GER). For example, suppression of gastric emptying and gastric motility would be expected to increase GER, and treatment with gastrokinetic agents appears to provide symptomatic improvement. However, only a fraction of patients with GER have delayed gastric emptying, and there is no correlation between either subjective epigastric fullness or esophagitis on one hand and gastric emptying on the other hand. Gastric acid and pepsin, and possibly the hypersecretion of acid, play a pivotal role in reflux esophagitis, as demonstrated by the efficacy of the treatment with histamine H2 antagonists and antacids. Other important factors in experimental esophagitis are duodenogastric reflux, the presence of bile acids in the gastric contents, as well as trypsin if the pH is alkaline. It is suggested that these important findings may lead to novel therapeutic approaches of reflux esophagitis. PMID- 3090135 TI - Experimental esophagitis in a rabbit model. Clinical relevance. AB - Esophagitis occurs in patients with excessive acid and/or alkaline gastroesophageal reflux. This observation prompted us to develop a continuously perfused in vivo rabbit esophageal model to examine the potential for different endogenous injurious agents to cause H+ back diffusion and morphologic evidence of esophagitis. We found that HCl at physiologic pH values did not break the mucosal barrier to H+ back diffusion or cause esophagitis. Bile salts at physiologic concentrations in both an acid or alkaline perfusate broke the mucosal barrier and caused H+ back diffusion, but failed to cause a morphologic injury consistent with clinical reflux esophagitis. Instead, proteolytic enzymes, such as pepsin in an acid environment and trypsin in an alkaline environment, caused a severe hemorrhagic erosive esophagitis consistent with that seen clinically. We feel new therapeutic strategies for the treatment of reflux esophagitis should be directed at proteolytic enzymes rather than only HCl or bile salts. Finally, we showed sucralfate to be a mucosal protectant against the acid-pepsin injury. PMID- 3090136 TI - Interactions of lectins with specific cell types in toad urinary bladder. Surface distribution revealed by colloidal gold probes and label fracture. AB - Colloidal gold probes were used in conjunction with pre-embedding labeling and label-fracture to show the plasma membrane distribution of Helix pomatia lectin (HPL) and wheat germ lectin (WGL) binding sites on different epithelial cell types of toad urinary bladder. Mitochondria-rich cells were virtually unlabeled with HPL, but showed a strong affinity for WGL. Granular cells were weakly labeled with WGL but had a variable affinity for HPL. Strongly labeled granular cells were arranged in either chains or clusters that were surrounded by poorly stained granular cells. By label-fracture, the distribution of gold-labeled lectins was related to other membrane features seen in freeze-fracture. Neither HPL nor WGL binding sites appeared to be specifically related to the large intramembrane particles that characterize granular cells, or to the rod-shaped intramembrane particles that are a feature of membranes of mitochondria-rich cells. The preferential lectin binding affinity of these functionally distinct cell types provides an important starting point for their isolation and the characterization of their plasma membranes. Furthermore, the label-fracture approach can now be used to examine the plasma membrane modifications that occur in these cells under different physiologic conditions affecting epithelial transport processes. PMID- 3090137 TI - An evaluation of various working practices in shops selling raw and cooked meats. AB - Three groups of premises (butchers' shops, supermarkets and general dealers) which sell raw and cooked meats were compared. Salmonellas were not detected, but Escherichia coli, and to a lesser degree Staphylococcus aureus and Streptococcus faecalis, were widely distributed in all three groups of premises. Contamination of hands, towels and nail brushes was related to poor working practices. The presence of E. coli or Str. faecalis on slicing machines was associated with contamination of meat samples. A number of wiping cloths were heavily contaminated with E. coli, and many also contained Clostridium perfringens. Fewer premises provided written cleaning plans, and in many cases staff did not receive an adequate training in food hygiene. The use of disinfectants as part of the cleaning process did not necessarily reduce the level of bacterial contamination. In general there was poor correlation between microbiological results and a visual inspection made by an environmental health officer. The possible reasons for this finding are discussed. PMID- 3090138 TI - Relative importance of sympathetic nerves and of circulating adrenaline and vasopressin in mediating hypertension after lesions of the caudal ventrolateral medulla in the rat. AB - Electrolytic lesions of the A1 noradrenaline cells in the caudal ventrolateral medulla cause transient hypertension and bradycardia in the conscious rat, as previously described in the rabbit. The lesions produced 100-fold increases in plasma arginine vasopressin, 40-fold increases in plasma adrenaline and fourfold increases in plasma noradrenaline levels. Absence of circulating vasopressin [homozygous diabetes insipidus rats (DI)] or circulating adrenaline (adrenalectomized rats) did not affect A1 hypertension, but sympathectomy with systemic 6-hydroxydopamine (6-OHDA) significantly attenuated A1 hypertension. A factorial experiment was performed to assess the relative contributions of these three peripheral effector mechanisms in a quantitative manner, with combined deficiencies of any two or of all three of these effector systems. Results suggest A1 hypertension in the rat to be primarily mediated through increased sympatho-adrenal activity. The largest component of hypertension (66%) results from increased sympathetic vasoconstrictor nerve activity, and a smaller part (34%) reflects the action of circulating adrenaline. Increases in vasopressin levels do not contribute to A1 hypertension, although vasopressin makes a major contribution to A1 lesion bradycardia. PMID- 3090139 TI - Induction of immune tolerance by administration of monoclonal antibody to L3T4. AB - Immune responses can be profoundly altered in mice by treatment with monoclonal antibodies (MAb) to L3T4, the mouse homologue for the CD4 antigen in humans. Treatment of mice with anti-L3T4 blocks both primary and secondary immune responses, delays allograft rejection, and retards autoimmunity. To determine whether anti-L3T4 could also be used to induce tolerance, we investigated the effect of treatment with rat MAb to L3T4 on the immune response to two other rat MAb: MAb to chicken egg ovalbumin (OVA) and MAb to T200, an antigen expressed on all mouse mononuclear blood cells. Treatment with anti-L3T4 prevented the primary humoral response to both of these MAb. Moreover, the anti-L3T4 MAb induced tolerance to itself, and it induced tolerance to the anti-OVA MAb when the two MAb were given concurrently. However, anti-L3T4 did not induce tolerance to the anti-T200 MAb when these MAb were given concurrently. These findings indicate that treatment with MAb to L3T4 may provide a new method for inducing tolerance to some, but not all, antigens. Because L3T4 in mice is homologous to CD4 in humans, our findings suggest that it may be possible to use anti-CD4 to induce tolerance to specific xenogeneic MAb, thereby facilitating their use as therapeutic agents in people. PMID- 3090140 TI - Polyclonal B cell activation by B cell differentiation factor B151-TRF2. I. Involvement of self-Ia recognition process mediated by B cells. AB - The present study examined the functional role of Ia antigens on B cells in polyclonal B cell activation induced by a B cell differentiation factor, B151 TRF2. The polyclonal IgM PFC responses by B151-TRF2 were inhibited by monoclonal antibodies specific for class II MHC antigens (Ia antigens) but not class I MHC antigens. Such inhibition by anti-Ia antibodies was haplotype-specific and was observed in the absence of both T cells and accessory cells. Moreover, the anti Ia antibody-induced inhibition of the B151-TRF2 responses was not due to the blocking of binding of B151-TRF2 to the corresponding B cell receptor. A series of kinetic studies revealed that some Ia-mediated cellular activation process occurs before the resting B cells become responsive to B151-TRF2. Thus, the B151 TRF2-mediated B cell responses consist of at least two distinct phases. The early phase is an Ia-dependent but B151-TRF2-independent process, whereas the late phase is an Ia-independent but B151-TRF2-dependent process. To further characterize the functional role of Ia antigens on B cells, an additional experiment was carried out by using F1 B cells which co-dominantly express both parental Ia antigens on the surface. Interestingly, it was observed that the degree of inhibition of the B151-TRF2-mediated responses of F1 B cells by anti parental Ia antibody was, at best, one-half that of the parental B cells, suggesting that F1 B cells may be separated into two subpopulations with the restriction specificity for the respective parental Ia antigens. To examine this possibility, (B10 X B10.BR)F1 B cells were separated into adherent and nonadherent cell populations by their ability to bind to either one of the parental B cell monolayers, and the specificity of inhibition of their responses to B151-TRF2 by anti-Ia antibodies was assessed. It was found that the responses of (B10 X B10.BR)F1 B cells adherent to the B10 B cell monolayer or the B10.BR B cell monolayer were almost completely inhibited by anti-I-Ab and anti-I-Ak antibodies, whereas those of nonadherent cells were now selectively inhibited by anti-I-Ak and anti-I-Ab antibodies, respectively. These findings are interpreted as indicating that the B151-TRF2-responsive F1 B cells consist of at least two subpopulations with the restriction specificity for either one of the parental Ia antigens.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3090141 TI - Transient modulation and internalization of T4 antigen induced by phorbol esters. AB - Phorbol esters are known to alter the expression of surface antigens and receptors on a variety of mammalian cell types. On T lymphoblastoid cell lines and peripheral blood T cells, phorbol esters have been shown to selectively reduce the expression of the T4 antigen. To more fully characterize this process, we have examined the metabolic requirements for this phorbol ester effect, and have evaluated the relationship between phorbol ester-induced T4 loss and the expression of receptors for phorbol-12,13-dibutyrate (PDB) on purified peripheral blood T4 cells. We observed that the loss of T4 on peripheral blood lymphocytes (PBL) occurred at PDB concentrations at which 10 to 15% of phorbol ester binding sites were occupied. The loss of T4 was inhibited at 4 degrees C, and by azide, methylamine, and sodium fluoride, but not by inhibitors of DNA synthesis. When cells were exposed to phorbol esters for greater than 2 days, the T4 antigen was again expressed on the cell surface despite the continued presence of phorbol esters. Cells which had recovered T4 were resistant to the effects of freshly added PDB on this antigen, and this resistance correlated with a 55% reduction in phorbol ester binding sites. Studies on fixed PBL T4 cells and MOLT-4 cells by immunofluorescence microscopy demonstrated that the decreased expression of T4 from the cell surface correlated with a bright clustering of T4 within the cytoplasm, indicating that PDB had induced an internalization of this antigen. These observations demonstrate that the binding of phorbol esters to specific receptors on lymphocytes initiates metabolically dependent events which result in the internalization of the T4 antigen. These findings may be relevant to mechanisms by which T4 functions as a signal-transducing molecule in vivo. PMID- 3090143 TI - Identification of an early activation antigen (Bac-1) on human B cells. AB - We have produced a monoclonal antibody, Bac-1, that appears to identify a novel antigen on activated human B cells. The Bac-1 antigen can be detected between 8 to 16 hr, as well as transferrin receptors (T9), after activation of small resting B cells with phorbol myristic acetate, anti-IgM antibody, Staphylococcus aureus Cowan I, or Epstein-Barr virus. The expression of the Bac-1 antigen precedes that of IL 2 receptors (Tac-1). Peak expression of the Bac-1 antigen was observed on day 3 after activation, and decreased thereafter. The Bac-1 antigen was present on a minor subpopulation of relatively large B cells isolated from blood samples, and on "preactivated" B cells of heterogeneous size isolated from spleens and tonsils. It was not detected on bone marrow pre-B cells, blood small B cells, or plasma cells, nor was it expressed by resting or activated T cells or nonlymphoid cells. Certain B cell neoplasms and B lymphoblastoid cell lines were Bac-1+, but neoplastic cells of non-B lineage were Bac-1-. With immunoperoxidase staining, Bac-1+ cells were detected predominantly in the germinal centers of tonsil sections. The Bac-1 antigen on activated B cells was destroyed by protease treatment and was enhanced by neuraminidase treatment, suggesting that the Bac-1 antibody detects a cell surface molecule via an antigenic determinant which is partially obscured by neighboring sialic acid residues. The reactivity pattern of Bac-1 differs from the patterns of cellular reactivity reported for other monoclonal antibodies with specificity for activated human B cells. PMID- 3090142 TI - Biosynthesis and surface expression of T8 by peripheral blood T4+ cells in vitro. AB - Biosynthetic labeling with 35S-methionine and 35S-cysteine of isolated T4+ cells from Con A-activated T cells demonstrated that the T8 antigen was synthesized by activated T4+ cells. Two-color fluorescence analysis of the activated T cell population from which the T4+ fraction was obtained showed that both T4+T8- and T4+T8+ cells were present. The T8 antigen that was immunoprecipitated by monoclonal anti-T8 from activated T4+ cells migrated with an electrophoretic mobility corresponding to an m.w. of approximately 33,000, a previously reported m.w. value for T8 antigen. Con A activation of highly purified peripheral T4+T8- and T8+T4- subsets indicated that both T4+T8- and T8+T4- cells can give rise to T4+T8+ cells. However, substantial T4, T8 coexpression by T4+T8- cells required a signal from T8+T4- cells which could be supplied by incubating T4+T8- cells with irradiated T8+ cells or the supernatant from Con A-activated T8+T4- cells. The generation of T4+T8+ cells from a subset of T4+T8- T cells may be an important mechanism in immune activation and/or the further differentiation of peripheral T4+ cells. PMID- 3090144 TI - Interleukin 1-dependent induction of both interleukin 2 secretion and interleukin 2 receptor expression by thymoma cells. AB - The macrophage-derived product, interleukin 1 (IL 1) is thought to play an important regulatory role in the proliferation of T lymphocytes; however, its mechanism of action is unknown. We describe in this report a variant subline of EL4 thymoma cells (EL4-6.1) that displays a high degree of responsiveness to IL 1. We show that recombinant IL 1 can induce both the secretion of interleukin 2 (IL 2) and the expression of IL 2 receptors (IL 2-R) by these cells. EL4-6.1 cells do not constitutively secrete IL 2, nor do they express IL 2-R; but when cultured in the presence of recombinant IL 1, they secrete detectable amounts of IL 2 (5 to 15 U/ml). In the presence of either suboptimal levels of phorbol ester (PMA) or Ionomycin, the addition of IL 1 resulted in up to an 80-fold enhancement in the amount of IL 2 secreted. Stimulation with IL 1 alone or in combination with Ionomycin was unable to induce detectable IL 2-R expression by EL4-6.1 cells. However, in the presence of suboptimal concentrations of PMA, IL 1 induced expression of about 3000 high affinity (dissociation constant, Kd of 31 pM) and 50,000 low affinity (Kd of 2800 pM) IL 2-R. These IL 2-R were functional, based on their ability to rapidly internalize IL 2. This model system will allow a detailed analysis of the mechanisms involved in the regulation of the immune response by IL 1 and IL 2. PMID- 3090145 TI - Natural killer cells are deficient in the surface expression of the complement regulatory protein, decay accelerating factor (DAF). AB - Decay-accelerating factor (DAF) is a 75,000 m.w. membrane protein that inhibits autologous complement C3 activation at the cell surface. One-color direct immunofluorescence with anti-DAF antibody and cytofluorographic analysis indicates that normal human monocytes and granulocytes are uniform in expression of DAF, whereas 23% of peripheral blood lymphocytes are DAF deficient. A two color indirect immunofluorescence method, used to define the phenotype(s) of the DAF-deficient lymphocytes, was less efficient in DAF detection and led to overestimation of the fraction of deficient cells. Nonetheless, the difference between DAF expression by natural killer cells, identified by the CD16 and HNK-1 antigens, was marked. DAF deficiency was intermediate in cells expressing the CD2, CD3, CD4, or CD8 markers. On the basis of the phenotypic definition of natural killer cells and their contribution to the lymphocyte population, it is concluded that a uniform deficiency of DAF on natural killer cells accounts for about one-half of the DAF-deficient lymphocytes in peripheral blood of normal donors. The finding of a complete DAF deficiency in the lymphocytes from a patient with a lymphoproliferative disorder with the predominant proliferation of CD2+, CD3+, CD8+, HNK-1+ large granular lymphocytes gives additional support for the association of DAF-deficiency with natural killer cells. PMID- 3090146 TI - Trypanosoma cruzi: characterization and isolation of a 57/51,000 m.w. surface glycoprotein (GP57/51) expressed by epimastigotes and bloodstream trypomastigotes. AB - We have recently described the application of a purified glycoprotein of 25,000 Mr (GP25) of Trypanosoma cruzi in serodiagnosis of Chagas' disease. Purified GP25 lacks appreciable immunogenicity in some animal species, in spite of being generally antigenic to parasitized hosts. The underlying cause for these contrasting observations has not been determined, but it may relate to the drastic extraction conditions used in the original isolation procedure, and possible damage inflicted to the native form of this antigen. This report describes the molecular properties of a GP25-related primary antigen, and a fast performance liquid chromatographic (FPLC) procedure to attain its isolation under gentle conditions. The expression of GP25-related antigen by epimastigotes or bloodstream forms was investigated with a high-affinity monoclonal antibody to GP25, SC11G10, as well as with monospecific antisera to GP25. Immunochemical analysis of Nonidet P-40 lysates supplemented with protease inhibitors indicated that GP25 is not synthesized as such; instead, a 57,000 Mr component (GP57) was identified as the primary antigen product. Partial enzymatic conversion to GP25 was observed when inhibitors were deliberately omitted from cell extracts. Most significantly, GP57 was established as the primary biosynthetic product in [35S] labeled bloodstream trypomastigotes after immunoprecipitation with SC11G10 antibody. This analysis when applied to metabolically labeled epimastigotes has consistently revealed a minor antigen component of 51,000 Mr (GP51), in addition to GP57. The former was identified as the antigenically related product exposed at the parasite cell surface after external radioiodination of viable trypanosomes. Access to the native form of this widely distributed surface glycoprotein should stimulate the investigation of functional and structural aspects of its immunologic activity. PMID- 3090147 TI - Bone marrow-derived macrophage expression of endogenous and transfected class II MHC genes during differentiation in vitro. AB - C57BL/6 (H-2b) mice fail to express I-E molecules on the surface of their cells and thus are unable to respond to I-E-restricted antigens such as GL phi and cytochrome c. Previous experiments in our laboratory have involved developing a system for studying differentiation of bone marrow cells into mature macrophage to gain a better understanding of class II MHC gene expression and function. In this study, we have used this system to transfect the E alpha d gene (cosmid 17.2) into C57BL/6 bone marrow cells and subsequently observed I-E expression on bone marrow-derived macrophages (BMDM) after differentiation in vitro. By using a modified calcium phosphate protocol, we found that the optimal period for transfection of the bone marrow cells was after 2 days of culture in vitro. By using the anti-I-E monoclonal antibody (Ia.7) derived from hybridoma 14-4-4, we detected the I-E molecule on the surface of transfected macrophages by a radiobinding assay and immunoprecipitation. BMDM expressed the I-E product maximally at 5 days of differentiation, and expression then declined. Furthermore, we have found that the expression of the I-E molecule on transfected macrophage was dependent upon exposure to interferon-gamma. Expression of I-E molecules was also detected by the generation of an allogeneic response. Transfected BMDM were compared with (CB6)F1 BMDM for their ability to stimulate C57BL/6 T cells and they were found to be equally effective. By using these initial findings, we hope to further optimize the conditions for insertion and expression of class II MHC genes in bone marrow cells. PMID- 3090148 TI - Protein changes associated with stages of activation of mouse macrophages for tumor cell killing. AB - Bone marrow-derived mouse macrophages become activated for tumor cell killing by traversing a series of stages. The stages studied here were as follows: unstimulated (exposed to nothing but medium), primed (prepared to become cytolytic), fully activated (primed macrophages exposed to a triggering agent), and postcytolytic (previously activated macrophages that had gradually lost cytolytic activity after the removal of stimuli). Macrophages were labeled with [35S]methionine, lysed, and subjected to 2-D gel electrophoresis and fluorography. The priming agent used was recombinant mouse IFN-gamma, 10 to 20 U/ml. Bacterial lipopolysaccharide (LPS), 0.4 to 1 ng/ml, was used as the triggering agent. A total of 40 major changes was identified in macrophages treated with both agents. Twenty-six of these were seen in macrophages treated with IFN-gamma, and 35 were found in LPS-treated macrophages. Twenty-two of the 40 changes were found in both IFN-gamma- and LPS-treated macrophages. The major reason for this overlap was the autocrine action of IFN-alpha/beta secreted from LPS-treated macrophages. Changes in expression of specific proteins, designated p47b and p71/73, were found to correlate closely with the development and loss of the activated state. With the use of these proteins as markers, phenotypes could be constructed that distinguished unstimulated, LPS-treated, primed, and fully activated macrophages. Postcytolytic macrophages had a phenotype similar to unstimulated macrophages and could be reactivated by reexposure to inducing agents. They also reexpressed the protein markers that were characteristic of fully activated macrophages. PMID- 3090149 TI - Immunohistologic analysis of lymphoid cells by a rapid double staining method. AB - The development of monoclonal antibodies has allowed characterization of subpopulations of lymphoid cells and of their in situ distribution in tissues. The feasibility of simultaneous localization of two surface antigens was studied by double staining with monoclonal antibodies to B cells, T cell subsets and follicular dendritic reticulum cells (DRC) using the avidin-biotin-complex (ABC) method in sections of human lymphoid tissues (tonsil, lymph node, spleen) and a non-lymphoid tissue, endometrium. Color mixture was avoided when an additional incubation with avidin-biotin-labeled peroxidase and subsequent development in the respective substrate of the first sequence preceded the second staining sequence using the primary antibodies at optimal concentrations. The antigenic profiles were portrayed by contrasting and distinct colors of the reaction products. It was observed that T lymphocytes of the cytotoxic/suppressor and helper/inducer phenotypes were topographically associated with each other and with B cells in B and T cell areas of lymphoid tissues as well as in lymphocytic aggregates in endometria. Subpopulations of these cells were mantled by processes of DRCs in lymphoid follicles. The findings indicate that the double ABC staining method can be used for simultaneous demonstration of two surface antigens in tissue sections. PMID- 3090150 TI - New micro-glass-tube leukocyte adherence inhibition assay assessing cell adherence of mononuclear cell subpopulations defined by monoclonal antibodies. AB - A new micro-glass-tube leukocyte adherence inhibition (LAI) assay which is appropriate for detecting delayed type hypersensitivity in vitro has been developed for human leukocytes. Enumeration of adherent cells is replaced by a cellular radioimmunoassay determining antibody binding of the monoclonal reagents, OKT4, OKT8 and OKM1, to glass-adherent cells, fixed by glutaraldehyde or formaldehyde. An LAI reactivity to purified protein derivative of tuberculin (PPD) was detectable in donors giving a positive PPD skin test with OKT4 reagent, but not with the other two reagents. PMID- 3090151 TI - Enumeration of the T4 positive and T8 positive lymphocytes in AIDS and related syndromes. Comparison of the immunogold and the immunofluorescence techniques. AB - Immunofluorescence and immunogold techniques yielded similar results when used to determine the T lymphocyte subsets (T4 and T8 positive cells) in patients with AIDS or AIDS-related complex and in healthy homosexual men seropositive for HTLV III/LAV antibody. In these pathological situations, the advantages of immunogold staining could render this technique useful in a clinical laboratory. PMID- 3090152 TI - The effect of coumermycin on experimental listeriosis. AB - The in vitro susceptibilities of Listeria spp. to coumermycin and novobiocin were tested. Coumermycin (0.015-0.12 mg/l) displayed lower minimum inhibitory concentrations than novobiocin (1-2 mg/l). There was only a narrow range of susceptibilities among 52 strains of Listeria spp. Bactericidal activity, however, could not be found. The in vivo activities of coumermycin were tested in mice. In normal adult mice infected with a virulent strain of L. monocytogenes the bacterial counts decreased rapidly after parenteral treatment with 2 mg twice daily but not after oral administration of 4 mg twice daily. Bacterial eradication was so effective that an immune response was prevented. Even in congenitally athymic mice a complete cure could be achieved. PMID- 3090153 TI - Pulmonary infection in cystic fibrosis. PMID- 3090154 TI - An endemic focus of murine typhus in Europe. PMID- 3090155 TI - Basement membranes in experimentally induced skin tumors. AB - Basement membrane changes in the epidermis and hair follicle apparatus resulting from topical 9,10-dimethylbenzanthracene applications were studied in mice, rats, and hamsters by light and electron microscopy and using antibodies to human collagen type IV and laminin. The basement membrane was distinct in epidermal hyperplasia, dysplasia, and papillomas, as well as around most of the keratoacanthomas and squamous cell carcinomas, which showed basement membrane irregularities, thickening, and reduplication in some areas. The invading edges of the squamous cell carcinomas with inflammatory infiltrates were devoid of laminin and collagen. Collagen IV and laminin-positive structures were observed around preserved follicular structures in rat: hair nevi and hair-follicle nevi, but partly absent around trichoepitheliomas and trichofolliculomas. Basal cell tumors were usually surrounded by a distinct basement membrane, which was lacking around some tumor cells. PMID- 3090156 TI - Lipid composition of cultured murine keratinocytes. AB - The current study was undertaken to determine whether a previously reported murine culture system is an acceptable model for the study of epidermal lipid metabolism. The lipid composition of primary neonatal mouse keratinocyte cultures was determined and compared with that of freshly isolated keratinocytes and whole epidermis. 14C-Labeled arachidonic acid (AA) and linoleic acid (LA) were added to cultures and the incorporation into specific lipids was assessed. The lipid composition of the cultures indicated that they were partially differentiated, which parallels the well-known incomplete keratinization seen in many keratinocyte culture systems. Of particular importance, the LA-rich uniquely epidermal lipids which may be of importance in water barrier function, acylglucosylceramide (AGC) and acylceramide (AC), were made by the cultures. Fatty acid analysis of total lipid, phospholipid, and AGC extracts revealed a significant decrease in LA content compared with the parent epidermis; this may have resulted from the low level of LA in fetal bovine serum, which was the serum source for these cultures. Labeled AA and LA were incorporated into the lipids of cultured keratinocytes in distinct patterns that were consistent with the fatty acid content of the lipids. Both AGC and AC showed preferential uptake of LA compared with AA. There was minimal labeling of non-linoleate-containing lipids and a low degree of conversion of labeled LA to AA. Considering the grossly different environment of the in vitro system compared with the in vivo state, the overall lipid composition was remarkably well maintained. Keratinocyte cultures should be of great value in the study of epidermal lipid metabolism. PMID- 3090157 TI - Cutaneous tissue repair following CO2 laser irradiation. AB - We studied the mechanism of repair following exposure of normal skin to the CO2 laser in a focused mode. Exposed areas were biopsied at 0, 24, 48 h; 1, 2 weeks; 1, 2 1/2 months (pulse width varying from 0.1 to 1.0 s) after irradiation. The initial pattern was a V-shaped zone of cauterized collagen with a central crevice, the depth of which correlated with the total energy applied. The epidermal changes consisted of transepidermal cauterization and basal vacuolar changes lateral to the site of impact. Over a period of 1 week, the wound crevice decreased in depth and width and the central margins of the zone of cauterized collagen approximated. The cauterized collagen was extruded and was noted in the epidermal crust; minimal granulation tissue was present. Biopsies at later time periods showed formation of granulation tissue and retention of small amounts of necrotic collagen; the process of collagen extrusion was largely prevented by suturing. These observations show that dermal contraction and necrotic collagen extrusion are important components of initial tissue repair following limited dermal destruction produced by CO2 irradiation. PMID- 3090158 TI - HLA-DR and melanoma-associated antigen (p97) expression during the cell cycle in human melanoma cell lines, and the effects of recombinant gamma-interferon: two color flow cytometric analysis. AB - Using monoclonal antibodies, recombinant human gamma-interferon, and fluorescence activated cell sorter, 2 human melanoma cell lines (KHm-1/4 and A101D) were examined quantitatively for HLA-DR and 97-kD melanoma-associated antigen (p97) expression throughout the cell cycle. Two-color flow cytometric analysis showed that the mean cell volume increased (KHm-1/4, 2.6 times; A101D, 3.6 times) during the progression of the cell cycle, and that fluorescence intensity of HLA-DR and p97 correlated well with cell volume, i.e., both antigens were maximally detected during the G2-M phase. The density of HLA-DR and p97 on the cell surface remained relatively constant throughout the cell cycle with the exception that cells in S phase showed a slightly lower density compared with those in G0/G1 and G2-M phases. gamma-Interferon treatment (500 IU/ml, 72 h) increased HLA-DR+ cells (KHm 1/4, 65% to 89%; A101D, 34% to 84%) and p97+ cells (KHm-1/4, 8% to 12%; A101D, 19% to 35%). Increased antigen densities were also relatively constant throughout the cell cycle as in nontreated cells. Cells treated with gamma-interferon tended to accumulate at G0/G1 phase (KHm-1/4, 21% to 37%; A101D, 17% to 53%), and had a reduced cell volume (0.82-0.95 times) throughout cell cycle. This study revealed that both melanoma cell lines showed heterogeneity in the expression of HLA-DR and p97, and that this heterogeneity was influenced, at least in part, by cell cycle and immunologic events such as gamma-interferon treatment. PMID- 3090159 TI - Intermittent hyperbaric oxygen therapy for reduction of mortality in experimental polymicrobial sepsis. AB - Hyperbaric oxygen therapy has a marked beneficial effect in experimental intraabdominal sepsis. Two rat models involving implantation of either rat fecal material or a mixture of pure cultures of Escherichia coli, Streptococcus faecalis, and Bacteroides fragilis were used in this study. A death rate of 100% was obtained in control animals implanted with fecal material; with intermittent hyperbaric oxygen treatment, a death rate of only 8% was observed (P less than .005). With a mixture of pure cultures of clinical pathogens, the death rate in control animals was 79%, and intermittent hyperbaric oxygen treatment reduced the rate to 23% (P less than .005). Data from cultures of blood indicated that the efficacy of hyperbaric oxygen was not related to antibacterial activity. PMID- 3090160 TI - Monoclonal antibodies to the cellular and scrapie prion proteins. PMID- 3090161 TI - Primary peritonitis due to Neisseria meningitidis serogroup W135. PMID- 3090162 TI - [A well-controlled comparative study on ceftriaxone with cefotaxime in respiratory tract infections]. PMID- 3090163 TI - [Factors contributing to the prognosis of tetanus]. PMID- 3090164 TI - [Study on production of toxic shock syndrome toxin in Staphylococcus aureus isolated from clinical specimens]. PMID- 3090165 TI - [Serologic studies of spotted fever group rickettsiosis occurring in Muroto-city, Kochi Prefecture]. PMID- 3090166 TI - [Hepatic injury due to typhoid and paratyphoid fever]. PMID- 3090167 TI - [Relation of growth type in soft-agar to the biological properties of fresh isolates of strains of Acinetobacter anitrautus]. PMID- 3090168 TI - [Recent observation on sepsis in infancy and childhood (1980-1984). Part 2. The survey through questionnaires in forty eight pediatric institutions in Japan, with reference to prognosis, underlying diseases and complications]. PMID- 3090169 TI - [Clinical studies on 72 cases with empyema in infants and children--review of a 10-year experience]. PMID- 3090170 TI - [A case of toxic shock syndrome]. PMID- 3090171 TI - [A case of cryptococcal meningitis successfully treated by ketoconazole and amphotericin B combination therapy]. PMID- 3090172 TI - [Detection of HBV DNA in the sera of HBV carriers by spot hybridization test]. PMID- 3090173 TI - [Chlamydia trachomatis infection in maternal and infants]. PMID- 3090174 TI - [Intervillous blood-gas status, especially oxygenation during cesarean section]. AB - Intervillous (IV), arterial (MA), and umbilical venous (UV) and arterial (UA) blood-gas values were measured in 36 healthy pregnant women. The patients were divided into three equal groups and underwent elective cesarean sections under spinal block. Oxygen was administered through a nasal cannula (group OL) or a mask (group OH), through group RA received no oxygen inhalation. Mean MAPO2 in each group was 102.0, 213.9 and 482.4 mmHg, respectively. Intervillous PO2 (Mean +/- SD mmHg) was 49.0 +/- 7.1 in group RA, 63.1 +/- 14.5 in group OL, 84.6 +/- 25.2 in group OH, oxygen saturation (%) was 83.2 +/- 6.0, 89.6 +/- 5.5 and 94.3 +/- 2.6, respectively, and oxygen content (CO2: ml/dl) was 12.7 +/- 0.9, 13.7 +/- 1.0 and 14.4 +/- 0.5, severely. There were significant differences in the intervillous oxygen values among the three groups. The intervillous acid-base value in group RA (pH: 7.389 +/- 0.013, PCO2: 33.9 +/- 2.3 mmHg and BD: 4.4 +/- 0.9 m mol/l) showed no significant differences from those of the other groups. Mean UVCO2 was somewhat greater than mean IVCO2 in any group due to the relatively higher oxygen affinity of fetal blood. Both IV and UVPO2 were not so elevated with oxygen inhalation and this was assumed to be due to characteristics of the oxyhemoglobin dissociation curve. The other results produce reliable evidence that placental circulation is not affected by maternal hyperoxia and that an increase in (IV-UA)PO2 facilitates oxygen transfer to the fetus. PMID- 3090175 TI - Enhanced expression of HLA antigens on gynecologic cancer cells by interferon gamma. AB - With flow-cytometry we tested whether or not interferon can induce surface expression of HLA-ABC antigen on cell lines derived from various gynecologic cancers. The tumor cell lines used were Hela S3 derived from cervical cancer, OVK 18 derived from ovarian cancer, HHUA derived from endometrial cancer, SCH, JaR and BeWo derived from choriocarcinoma. 1000 IU/ml of interferon-gamma induced HLA ABC antigen expression on Hela S3, OVK-18 and SCH but not on BeWo. HLA-ABC antigen was expressed on neither the surface of HHUA or JaR nor was its appearance induced by interferon. The clinical application of interferon may be effective in killing some tumors, taking advantage of the increased expression of HLA antigen. PMID- 3090176 TI - [Isolation and characterization of a metalloprotease associated with chicken epiphyseal cartilage matrix vesicles]. AB - Matrix vesicles are present in the calcifying front and in the site of callus formation of fracture heeling. In calcifying process, matrix vesicles have important roles. The metalloprotease was isolated from matrix vesicles and subsequently characterized. Matrix vesicles obtained from chicken epiphysial cartilage by collagenase digestion and differential centrifugation were further purified by Sepharose CL2B gel filtration. The protease was solubilized from the vesicles and isolated by Sephadex G-150 gel filtration. Disc electrophoresis of the enzyme gave a single protein band. The matrix vesicle protease had a MW of 33,000 daltons, an optimal pH of 7.2, and was inhibited 100% by 0.1 mM EDTA and 0.2 mM o-Phenanthroline. alpha 2-Macroglobulin, ovalbumin, cysteine, penicillamine, ethane-1-hydroxy-1, 1-diphosphonate (EHDP) and pyrophosphate at higher concentrations were also inhibitory. The inhibition by o-phenanthroline was reversed by Co2+, Zn2+, Fe2+ and Cu2+. The protease released from the matrix vesicle at the calcifying front could degrade non-collagenous protein moieties which inhibit precipitation of minerals in the extra-vesicular matrix and thus facilitate mineralization. PMID- 3090177 TI - Lipoxygenation of arachidonic acid by differentiated and undifferentiated human promyelocytic HL-60 cells. AB - The human promyelocytic leukemia cell line HL-60 can be induced to differentiate into mature granulocytes by exposure to dimethyl sulfoxide (DMSO), as well as into cells of monocyte-macrophage lineage by exposure to 12-0-tetra decanoylphorbol-13-acetate (TPA). Incubation of the promyelocytic leukemic HL-60 cells and the two chemically induced differentiated cells with carbon 14-labeled arachidonic acid overnight resulted in the incorporation of label mainly into cellular phospholipids. Stimulation of the labeled cells with Ca2+ ionophore (A23187) resulted in the generation of lipoxygenase products in all the cells. Notably, the DMSO-induced differentiated granulocytic cells biosynthesized predominantly the peptidoeicosatetraenoic acids LTC4 and LTD4 compared with the dihydroxyeicosatetraenoic acid LTB4. On the other hand, the TPA-induced differentiated monocytic-macrophage cells biosynthesized predominantly LTB4 compared with LTC4 and LTD4. The undifferentiated promyelocytic cells lacked the capacity to biosynthesize LTB4, as evidenced in the chemically induced differentiated cells. The monohydroxyeicosatetraenoic acid (HETE) 5-HETE, a metabolite of the 5-lipoxygenase pathway, was a minor component in these cells, and 12-HETE and 15-HETE were barely detectable. These results suggest that the two models of DMSO-induced and TPA-induced differentiated cells may be useful systems for further investigations of arachidonic acid metabolites in granulocytic and monocytic-macrophage functions. PMID- 3090178 TI - Human monocyte-released cytotoxic factor: effect on various cellular functions, and dependency of cytolysis on various metabolic processes. AB - The ability of the human monocyte-released cytotoxic protein factor(s) (CF) to mediate cytolysis when various metabolic processes in target cells were inhibited, and its effect on various cell functions have been studied. Cytolysis was reduced when target cells were exposed to either chloroquine or colchicine, indicating that lysosome function and the formation of microtubule are of importance with respect to the interaction between CF and target cells, possibly by effecting internalization and processing CF and its receptor. A decrease in the energy charge of the target cells did not affect the ability of CF to mediate cytolysis, since the 60-70% reduction of the cellular ATP content by uncoupling oxidative phosphorylation had little effect on CF-induced lysis. It was unnecessary for target cells to be actively growing and dividing for CF to induce lysis because inhibition of cellular protein, RNA, and DNA synthesis potentiated the cytolytic effect of CF. CF-induced cell lysis of Walter and Eliza Hall Institute (WEHI) 164 target cells was first detected between 3.0 and 4.5 hr after addition of CF. Target cell DNA synthesis nearly terminated within 3-4 hr, about the time of first cell lysis detection. Compared to the effect on DNA synthesis, the CF effect on protein synthesis was negligible and only a slight reduction was detected in the RNA synthesis and in the cellular ATP content. The results indicated that the DNA-synthesizing machinery may either be a primary target site of CF or a rapid influence of CF action on its primary target site; however, neither the protein- or RNA-synthesizing machinery nor the cellular ATP generating systems are likely to be primary target sites. PMID- 3090179 TI - Gender-related variations and interaction of human neutrophil cyclooxygenase and oxidative burst metabolites. AB - Gender-related variations in human neutrophil membrane bound oxidative metabolism were evaluated employing the calcium ionophore A23187. These included the measurement of cyclooxygenase metabolites of arachidonate by specific RIA determination of thromboxane B2 (TxB2), prostaglandin E2 (PGE2), and 6-Keto PGF1 (6KPGF) as well as the initiation of the oxidative burst by the quantitative evaluation of superoxide (O-2) reduction of nitroblue tetrazolium (NBT). Neutrophils from women generated 30% less TxB2 and PGE2 than those obtained from men. In contrast, the neutrophils from women demonstrated relatively higher O-2 production with a cyclic pattern of both TxB2 and O-2 which correlated with their menstrual cycle. The elevated O-2 generation appeared to inversely correlate with TxB2 production. Further, introduction of an intracellular oxygen centered radical (OCR) scavenger, sodium benzoate, for the hydroxyl (.OH) radical was observed to affect cyclooxygenase metabolism in a dose-response manner. At higher concentrations of sodium benzoate, i.e., 10(-2) M, TxB2 production was inhibited; in contrast, 10(-3) M sodium benzoate enhanced neutrophil TxB2 generation which was particularly marked during times of increased oxidative burst activity, i.e. O-2 production. We conclude that the decreased production of cyclooxygenase metabolites observed in neutrophils from women in part derive from an increased oxidative burst activity. This suggests that a regulatory mechanism may exist between the neutrophil membrane bound oxidative system(s) involving oxygen centered radicals generated during both the oxidative burst and prostaglandin cyclic endoperoxide reduction. Further, these gender-related differences may be partially attributable to variations in circulating endogenous sex steroids. PMID- 3090180 TI - High density lipoprotein-induced cardiac prostacyclin synthesis in vitro: relationship to cardiac arachidonate mobilization. AB - The objectives of this study were to characterize the effects of plasma lipoproteins on prostacyclin (PGI2) production by the Langendorff-perfused rabbit heart, and to determine the mechanism of lipoprotein-induced cardiac PGI2 production. PGI2 production by perfused rabbit hearts was stimulated by injections of rabbit very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL). HDL was much more effective than equivalent doses of VLDL or LDL. Infusion of HDL at a physiological concentration stimulated cardiac PGI2 output by 417%, but infusion of VLDL or LDL was ineffective. Cardiac PGI2 production increased from 47% to 340% with increasing doses of HDL. The release of cardiac PGI2 in response to injections or infusions of HDL occurred rapidly; maximal release of PGI2 was reached within 2 min after exposure to HDL. Injections of HDL stimulated the production of [3H]arachidonic acid, [3H]prostaglandin E2, [3H]prostaglandin F2 alpha, and [3H]6-keto-prostaglandin F1 alpha from hearts after prelabeling of cardiac lipids with [3H]arachidonic acid. These results indicate that plasma lipoproteins, specifically HDL, stimulate PGI2 production by the isolated rabbit heart. The mechanism by which HDL increases cardiac PGI2 production may involve the mobilization of cardiac arachidonic acid for PGI2 synthesis. PMID- 3090182 TI - Hypothyroidism of hypothalamic origin in pyridoxine-deficient rats. AB - Pyridoxine-deficient young rats (3 weeks old) had significantly reduced levels of pituitary TSH, serum thyroxine (T4) and tri-iodothyronine (T3) compared with pyridoxine-supplemented rats. The status of the pituitary-thyroid axis of normal, pyridoxine-supplemented and pyridoxine-deficient rats was evaluated by studying the binding parameters of [3H](3-methyl-histidine2)TRH in the pituitary of these rats. The effects of TRH and T4 injections on pituitary TSH and serum TSH, T4 and T3 of these two groups were also compared. The maximal binding of TRH receptors in the pituitary of pyridoxine-deficient rats was significantly higher than that of pyridoxine-supplemented control and normal rats, but there was no change in the binding affinity. Treatment with TRH stimulated TSH synthesis and release. It also increased serum T4 and T3 in both pyridoxine-supplemented and pyridoxine deficient rats. Treatment with T4 decreased serum and pituitary TSH in both pyridoxine-supplemented and pyridoxine-deficient rats, compared with saline treated rats. The increased pituitary TRH receptor content, response to TRH administration and the fact that regulation at the level of the pituitary is not affected in the pyridoxine-deficient rat indicates a hypothalamic origin for the hypothyroidism of the pyridoxine-deficient rat. PMID- 3090181 TI - High density lipoprotein accumulation in perfusates of isolated livers of African green monkeys. Effects of saturated versus polyunsaturated dietary fat. AB - To determine whether altered hepatic secretion of HDL is part of the mechanism by which polyunsaturated fat lowers plasma HDL concentration, we have studied HDL secretion in the isolated perfused livers of African green monkeys fed an atherogenic diet containing either safflower oil as the polyunsaturated fat or butter as the saturated fat. During recirculating perfusion with a lipoprotein free medium, livers from safflower oil-fed animals produced 21% less HDL mass on the average than those from butter-fed animals. Newly secreted hepatic HDL were characterized after their isolation and subfractionation by a combination of agarose column chromatography and density gradient ultracentrifugation. In both diet groups the HDL were heterogeneous in size, morphology, and composition and consisted of discoidal particles ranging in diameter from greater than 200 A to as little as 50 A. Large, discoidal particles that were rich in apoE and apoA-I were separated from small particles that were poor in apoE but rich in apoA-I. All hepatic HDL subfractions contained only small amounts of cholesteryl ester and triglyceride. The hepatic particles resembled in composition and structure the large variety of HDL particles found in the plasma of patients with the familial deficiency of lecithin:cholesterol acyltransferase. Accordingly, perfusate LCAT activity was measured and found to be 2% or less than that in monkey plasma. We conclude that the perfused monkey liver produces a variety of nascent HDL that are relatively unmodified by the post-secretory metabolic events which normally occur in blood plasma in vivo, and that livers of polyunsaturated fat-fed monkeys secrete fewer plasma HDL precursor particles than do those of saturated fat-fed monkeys. PMID- 3090184 TI - Effects of hypophysectomy and growth hormone infusion on rat hepatic carbonic anhydrases. AB - Rat liver exhibits a reversed sexual dimorphism of its two endogenous soluble carbonic anhydrase (CA) isozymes, CA II and CA III. Normal males have hepatic CA III concentrations ten-twenty times those in the female, while female liver contains two-three times more CA II than the male. Hypophysectomy abolishes this sexual differentiation, having no effect on male liver but producing isozyme concentrations in the female liver similar to those in the male. Infusion of a continuous level of GH into male rats induces a female-like isozyme pattern for both CA II and CA III. PMID- 3090183 TI - In-vitro secretion of inhibin-like activity by Sertoli cells from normal and prenatally irradiated immature rats. AB - The influence of in-vitro conditions on the production of inhibin by Sertoli cells from 21-day-old normal and prenatally irradiated rat testes was studied by measuring inhibin activity in culture media, using the suppression of the release of FSH from cultured rat pituitary cells. Sertoli cells secreted inhibin-like activity during at least 21 days of culture, and cells cultured at 37 degrees C produced significantly more inhibin than those cultured at 32 degrees C. The presence of fetal calf serum had no significant effect on inhibin production at 32 degrees C, while at 37 degrees C the production was decreased. The presence of ovine FSH stimulated inhibin secretion, while inhibin concentrations in Sertoli cell culture media were decreased after the addition of testosterone. Testosterone, added together with ovine FSH, suppressed inhibin secretion when compared with the levels found in the presence of FSH alone. The presence of spermatogenic cells decreased the release of inhibin. From these results it was concluded that both Sertoli cells isolated from normal immature rat testes and those from testes without spermatogenic cells can secrete inhibin-like activity in culture. A number of discrepancies with in-vivo observations was observed. Therefore, it is likely that the in-vivo situation is too complicated for direct study of the regulation of inhibin production, because of mutual interactions between the testicular compartments. PMID- 3090185 TI - Endocrine changes associated with the termination of photorefractoriness by short daylengths and thyroidectomy in starlings (Sturnus vulgaris). AB - When starlings (Sturnus vulgaris) are transferred from short to long days, hypothalamic content of gonadotrophin-releasing hormone (GnRH) and pituitary gonadotrophin content eventually decrease, as birds become photorefractory, to values lower than they were on short days. This implies that both should increase as photorefractoriness is terminated some time after transfer from long to short days. Further, since thyroidectomy causes termination of photorefractoriness in birds held on long days, this should also result in an increase in hypothalamic GnRH and pituitary gonadotrophin contents. This study tests these hypotheses. Male starlings were transferred from short to long days for 10 weeks, by which time they should have become photorefractory. One group of birds was then killed; blood was collected, hypothalami and pituitaries were excised, and the stage of moult and testicular weights recorded. The remaining birds were then kept on long days, transferred to short days or thyroidectomized and kept on long days. Groups of birds in each treatment group were killed and sampled 2, 8 and 14 weeks later. Hypothalamic content of GnRH, and pituitary and plasma FSH and prolactin concentrations, were measured by radioimmunoassay. In birds sampled after 10 weeks of long days, hypothalamic content of GnRH was quite low, pituitary and plasma levels of FSH were very low, testes were small and pituitary and plasma prolactin levels were high. In intact birds kept on long days, hypothalamic GnRH content decreased further and remained low. Pituitary and plasma FSH levels remained low, testes remained small and pituitary and plasma prolactin levels decreased slowly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090187 TI - Arachidonic acid metabolism in canine tooth pulps and the effects of nonsteroidal anti-inflammatory drugs. PMID- 3090186 TI - Development and steroidogenic activity of preantral follicles in the neonatal rat ovary. AB - The neonatal rat ovary is completely devoid of antral follicles until the twelfth day of age. During this period the ovary becomes steroidogenically active and responsive to gonadotrophins. The aim of this study was to correlate the onset of ovarian androgen and oestrogen production in vitro with the first appearance of distinct granulosa and theca cells. Although ovarian aromatase activity increased significantly on day 7 of age, ovarian oestrogen production was limited by low progesterone and testosterone production until day 12 of age. Increased aromatase activity on day 7 and androgen production on day 12 were coincident with the first appearance of granulosa and theca cells respectively. These functional and morphological changes were not associated with significant alterations in ovarian weight or concentrations of LH or FSH in serum. PMID- 3090188 TI - The effect of lethal mutations and deletions within the bithorax complex upon the identity of caudal metameres in the Drosophila embryo. AB - Mutations and deletions of the abdA and AbdB functions in the bithorax complex of Drosophila melanogaster have been examined for their effect upon the hypodermal derivatives of the caudal segments of the embryo, employing light- and scanning electron microscopy. No cuticular structures located posterior to the denticle belt of abdominal segment 8 are affected in abdA- embryos. Embryos of AbdB- genotype no longer have six of the seven pairs of sense organs present in this region, lack posterior spiracles but instead have sclerotized cuticle and sense organs typical of the head region and a rudimentary extra ventral denticle belt. The anal pads, tuft and sense organ 1 do not require BX-C functions for their specification. We discuss the provenance of these cuticular structures and the domain of function of elements within the bithorax complex in terms of parasegmental metameric units. PMID- 3090189 TI - The role of cell adhesion in the synchronization and orientation of polarization in 8-cell mouse blastomeres. AB - A detailed investigation into the activity of the homotypic, Ca2+-dependent cell cell adhesion system (CDS) in the early mouse embryo has revealed its involvement in the synchronizing of the time of polarization of 8-cell blastomeres, and the orienting of the axis of polarization. Since polarization marks an important and early event in the process of cell diversification in the mouse embryo, it is concluded that the CDS provides an important component of the system by which the temporal and spatial elements of normal development are integrated. PMID- 3090190 TI - Identification of glycosaminoglycans in the chondrocranium of the chick embryo before and at the onset of chondrogenesis. AB - It appears that hyaluronate is associated with cell migration and the chondroitin sulphates with differentiation during morphogenesis of the chick embryo. The aim of this study was to see if such a correlation could be made for chondrocranium morphogenesis. Specifically, the purpose of this study was to determine the proportion of extracellular matrix (ECM) to cell area and total head mesenchymal area during chondrocranium morphogenesis; and to identify the location, types, and relative amounts of glycosaminoglycans (GAG) being synthesized in the presumptive chondrocranium at the onset of chondrogenesis and prior to this time. Morphometric analyses were made on median and parasagittal sections of heads of stage-24 and -33 embryos in order to determine relative contributions of cells and ECM to the total area of head mesenchyme at these stages. Presumptive chondrocrania (heads minus eyes) of these stage embryos were also analysed histochemically and biochemically in order to identify the GAGs present in the ECM. Sections of whole heads were stained with alcian blue at low and high pH as well as digested prior to staining with hyaluronidase (Streptomyces and testicular). Identification of GAGs was done by pulse labelling embryos with [3H]glucosamine, digesting homogenates with hyaluronidase (Streptomyces or testicular), precipitating the undigested GAGs with cetylpyridinium chloride and counting the dissolved precipitates using scintillation spectrophotometry. The types and relative amounts of GAGs present in the presumptive chondrocranium were determined by comparing the amount of radioactivity in the precipitates of the non-digested GAG with the counts in the precipitates of the predigested GAGs. This study reports that chondrogenesis begins in the presumptive chondrocranium of the chick embryo at stage 33 and that the area of the head mesenchyme increases 60-fold between stages 24 and 33. Little change in cell density and individual cell area as well as in the relative proportion of total area allocated to cells and ECM occurs. GAGs are localized exclusively in the presumptive chondrocranium. These GAGs are restricted to the ventral half of the presumptive chondrocranium. Within this region, the GAGs are further localized to the presumptive facial area, perichordal region, ethmoid, sphenoid and periotic regions. The types of GAG being synthesized in the head mesenchyme of both stage 24 and -33 embryos are hyaluronate, the chondroitins and unidentified sulphated GAGs (dermatan, keratin, heparin and heparan sulphate).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3090191 TI - Modifications of size and pattern of microtubular organelles in overfed cells of a ciliate Dileptus. AB - The size of mouthparts and their constituent organelles was studied in cells of Dileptus anser, enlarged by overfeeding. The oral structures of large cells were either of normal dimensions and appearance, or they were enlarged and deformed in shape. The increase in size of mouthparts was accompanied by an increase in number of their microtubular organelles. There was, however, no net increase in size of the organelles, as defined by length and number of microtubules they contained. It is concluded that there exists an upward regulation in the size of the mouthparts as a whole, whilst the size of their constituent organelles is probably not so regulated. It is supposed that the patterning of normal-size organelles into large oral structure may lead to the observed deformations in the shape of the mouthparts. PMID- 3090192 TI - Effect of case mix on provider continuity. AB - A random sample of 265 patient charts was selected to assess the degree of provider continuity at the University of North Carolina Family Practice Center from July 1, 1983, to June 30, 1984. Continuity was measured using usual provider continuity, the ratio of the number of visits with the assigned physician divided by total visits. Usual provider continuity rates varied as predicted for three types of visits: acute illness (0.55), chronic illness (0.76), and health maintenance (0.86). The average rate of usual provider continuity was 0.68. Case mix had a statistically significantly effect on provider continuity when comparing acute care with either chronic or health maintenance care (P less than .01). Because case mix is relevant and varies from site to site, a method of rate standardization was suggested using data on case mix from the National Ambulatory Medical Care Survey. Direct rate adjustment, a standard epidemiologic technique, would make continuity rates directly comparable for sites with different case mixes. PMID- 3090193 TI - Low free and total thyroxines in nonthyroidal illnesses. PMID- 3090194 TI - [An appraisal of Rh(D) typing in Chinese]. PMID- 3090195 TI - Molecular size diversity of citrate synthases from Pseudomonas species. AB - Two forms of citrate synthase (EC 4.1.3.7) have been found in several species of Pseudomonas, a 'large' form (Mr congruent to 250,000) which is generally inhibited by NADH and reactivated by AMP, and a 'small' form (Mr congruent to 100,000) which is insensitive to these nucleotide effectors. Other species of Pseudomonas were found to contain either the 'large' or the 'small' form. Gel filtration and ion-exchange with the technique of fast protein liquid chromatography were used to resolve the enzymes. Where both citrate synthases were present, there did not appear to be an equilibrium between the two forms. The results reveal a new and complex diversity of citrate synthase within the genus Pseudomonas. PMID- 3090196 TI - Induction of interferon alpha and gamma from human lymphocytes by dengue virus infected cells. AB - Human peripheral blood lymphocytes (PBL) of non-immune donors produced interferon (IFN) when cultured with dengue virus-infected cells. IFN was detected as early as 2 h after exposure of PBL to dengue virus-infected cells, and the titres reached a maximum by 16 h of incubation. Dengue virus-infected cells treated with glutaraldehyde, which produced no infectious dengue virus, also induced IFN. These results indicate that PBL produce IFN in response to dengue virus-infected cells and that the production of IFN by PBL is due to stimulation of PBL by dengue virus-infected cells. Characterization of IFN-producing PBL with monoclonal antibodies demonstrated that the predominant producing cells were contained in M1+ and T3- subsets, and that the Leu11+ subset contains some IFN producing cells. The IFNs that were produced by the PBL exposed to dengue virus infected cells were analysed by radioimmunoassay employing monoclonal antibodies specifically to detect IFN-alpha or IFN-gamma. IFN-gamma as well as IFN-alpha was produced by PBL exposed to dengue virus-infected cells. Both IFN-alpha and IFN gamma were predominantly produced by PBL contained in M1+ and T3- subsets. The observation that PBL of non-immune donors produced IFN-gamma as well as IFN-alpha in response to dengue virus-infected cells is of interest in view of the immunoregulatory roles of IFNs and the hypothesis that the complications of dengue virus infection (haemorrhagic fever and shock) may be due to immunopathology. PMID- 3090197 TI - Immunoreactivity of a synthetic pentadecapeptide corresponding to the N-terminal region of the scrapie prion protein. AB - A pentadecapeptide with an amino acid sequence corresponding to the amino terminal region of the scrapie prion protein was synthesized. Immunization of a rabbit with the peptide conjugated with ovalbumin induced specific antibodies. The antibodies reacted with all three of the major polypeptides in a proteinase K treated fraction obtained from brains of mice infected with the Obihiro strain of scrapie agent. Some peptides in the proteinase-untreated fraction also shared antigenicity with the three major polypeptides. Specific polypeptides were also detected by the antiserum in a fraction prepared from spleens, but only two of the three major polypeptides were found and the amounts of the polypeptides were less than in brain. PMID- 3090198 TI - Apparent neuroleptic malignant syndrome with clozapine and lithium. AB - Clozapine is an antipsychotic drug reported to be virtually free of extrapyramidal effects. On the basis of this, we hypothesized that it would be unlikely to cause the neuroleptic malignant syndrome (NMS), a rare but severe reaction observed with other antipsychotic drugs. However, when we administered clozapine (in conjunction with lithium) to a patient with a past history of NMS with fluphenazine, the syndrome reappeared after about 3 weeks of treatment. This represents, to our knowledge, the first report of apparent NMS with clozapine. PMID- 3090199 TI - A case of bupropion-induced seizure. AB - Bupropion is a novel new antidepressant without the undesirable anticholinergic, cardiotoxic, sedative, or sexual side effects of other available antidepressants. However, like many other antidepressants, there is a small risk that patients on bupropion may develop a seizure even at moderate doses and moderate blood levels and even in the absence of any premorbid history or other predisposing factors to epilepsy. The report presents the case of a 25-year-old woman with a 12-year history of agoraphobia and panic attacks treated with bupropion in a research protocol. She was in good physical health, with normal physical and neurological examination, and normal complete blood count, serum mineral analysis-12, and urinalysis laboratory values. She had no premorbid history of epilepsy or neurological illness, nor any other known predisposing factors to epilepsy. On day 28 of the study, immediately after her dose of bupropion was increased from 450 to 600 mg/day, she had a generalized convulsion with tonic and clonic phases, loss of consciousness, and postictal confusion that was reliably witnessed by several observers. The EEG abnormality had cleared 15 days later. Further EEGs after 4 weeks and 10 weeks were normal. Five years later she remains seizure free, off all antiseizure medication, and without any further complications from this incident. This seizure occurred at a modest blood level of bupropion (83 ng/ml) and at a dose not considered excessive (600 mg/day). Other confounding organic and neurological illness or use of other medication was carefully and systematically ruled out, leaving the bupropion as the most likely explanation for her seizure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090200 TI - Mutual inhibition kinetic analysis of gamma-aminobutyric acid, taurine, and beta alanine high-affinity transport into neurons and astrocytes: evidence for similarity between the taurine and beta-alanine carriers in both cell types. AB - The transport kinetics of gamma-aminobutyric acid (GABA), taurine, and beta alanine in addition to the mutual inhibition patterns of these compounds were investigated in cultures of neurons and astrocytes derived from mouse cerebral cortex. A high-affinity uptake system for each amino acid was demonstrated both in neurons (Km GABA = 24.9 +/- 1.7 microM; Km Tau = 20.0 +/- 3.3 microM; Km beta Ala = 73.0 +/- 3.6 microM) and astrocytes (Km GABA = 31.4 +/- 2.9 microM, Km Tau = 24.7 +/- 1.3 microM; Km beta-Ala = 70.8 +/- 3.6 microM). The maximal uptake rates (Vmax) determined were such that, in neurons, Vmax GABA greater than Vmax beta-Ala = Vmax Tau, whereas in astrocytes, Vmax beta-Ala greater than Vmax Tau = Vmax GABA. Taurine was found to inhibit beta-alanine uptake into neurons and astrocytes in a competitive manner, with Ki values of 217 microM in neurons and 24 microM in astrocytes. beta-Alanine was shown to inhibit taurine uptake in neurons and astrocytes, also in a competitive manner, with Ki values of 72 microM in neurons and 71 microM in astrocytes. However, beta-alanine was found to be a weak noncompetitive inhibitor of neuronal and astrocytic GABA uptake, whereas in reverse experiments, GABA displayed weak noncompetitive inhibition of neuronal and astrocytic uptake of beta-alanine. Likewise, taurine was a weak noncompetitive inhibitor of GABA uptake in neurons and similarly, GABA was a weak noncompetitive inhibitor of taurine uptake into neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090201 TI - Solubilization and partial purification of a presynaptic membrane protein ensuring calcium-dependent acetylcholine release from proteoliposomes. AB - In previous work, it was shown that cytoplasmic acetylcholine decreased on stimulation of Torpedo electric organ or synaptosomes in a strictly calcium dependent manner. This led to the hypothesis that the presynaptic membrane contained an element translocating acetylcholine when activated by calcium. To test this hypothesis, the presynaptic membrane constituents were incorporated into the membranes of liposomes filled with acetylcholine. The proteoliposomes thus obtained released the transmitter in response to a calcium influx. The kinetics and calcium dependency of acetylcholine release were comparable for proteoliposomes and synaptosomes. The presynaptic membrane element ensuring calcium-dependent acetylcholine release is most probably a protein, since it was susceptible to Pronase, but only when the protease had access to the intracellular face of the presynaptic membrane. Postsynaptic membrane fractions contained very low amounts of this protein. It was extracted from the presynaptic membrane under alkaline conditions in the form of a protein-lipid complex of large size and low density which was partially purified. The specificity of the calcium-dependent release for acetylcholine was tested with proteoliposomes filled with equal amounts of acetylcholine and choline or acetylcholine and ATP. In both cases, acetylcholine was released preferentially. After cholate solubilization and gel filtration, the protein ensuring the calcium-dependent acetylcholine release was recovered at a high apparent molecular weight (between 600,000 and 200,000 daltons), its apparent sedimentation coefficient being 17S after cholate elimination. This protein is probably an essential coin of the transmitter release mechanism. We propose to name it mediatophore. PMID- 3090202 TI - Intractable unphysiologically low adenylate energy charge values in synaptosome fractions: an explanatory hypothesis based on the fraction's heterogeneity. AB - Synaptosomes prepared and incubated in a variety of ways from rat cerebra exhibited intractable, unphysiologically low adenylate energy charge values (approximately 0.37-0.60), low total adenine nucleotide contents (approximately 8 10 nmol/mg protein), and much higher adenylate kinase apparent Keq values (approximately 3-8) as compared to intact brain tissue (values of approximately 0.90, 25 nmol/mg, and 0.74, respectively). Synaptosomes prepared from mouse, dog, and chicken cerebra had values essentially identical to those from rat. When incubated under oxygen in a physiological salt solution containing glucose, synaptosomes metabolized more glucose to lactic acid than to CO2, and the addition of 100 microM veratridine caused a two- to threefold stimulation of O2 uptake, lactate accumulation, and CO2 output. It is known that synaptosome fractions contain a substantial number (at least 30-45% by volume) of cytoplasm containing particles devoid of mitochondria (henceforth termed "cytosolic particles"), and that approximately 80% of brain hexokinase is bound to the outer mitochondrial membrane. For the cytosolic particles, lacking oxidative phosphorylation, to maintain their "in vivo" ATP turnover would require about a 19-fold increase in the glycolytic rate, which is not possible due to limiting amounts of hexokinase, and thus these particles are postulated to be responsible for the high level of aerobic lactate accumulation and the intractable low energy charge values found in synaptosome fractions. The mitochondria-containing particles are postulated to have a normal energy charge, a submaximal glycolytic rate, and minimal lactate production, on the basis of the capacity of veratridine to stimulate synaptosomal O2 uptake and CO2 and lactate output. Calculations based on this "two populations of particles" hypothesis indicate that for synaptosome fractions in general, (1) the cytosolic particles contain approximately 35-64% of the total adenine nucleotides and maintain an energy charge of approximately 0.12; (2) the cytosolic particles and mitochondria containing particles have adenylate kinase apparent Keq values of approximately 0.21-1.66 and 0.74, respectively, revealing that the higher apparent Keq values of the synaptosome fractions probably are not real departures from equilibrium: and (3) approximately 31-45% of synaptosome fraction protein is contained in debris, which, when taken into account, yields total adenine nucleotide contents in the cytosolic particles and mitochondria-containing particles of approximately 15-24 and approximately 11-19 nmol/mg of particle protein, respectively. PMID- 3090203 TI - Developmental change in the glycosaminoglycan composition of the rat brain. AB - Glycosaminoglycans (GAGs) were isolated from the brains of pre-and postnatal rats. The GAG content of the brain, based on the amount of DNA, was constant during the period from day 13 to day 15 of gestation. After day 15, the GAG content began to increase and reached a plateau by 10 days after birth. Hyaluronate (HA) was the main GAG (greater than 60% of the total) in the fetal rat brain, and the relative amount of HA decreased after birth. Conversely, the relative amount of chondroitin sulfate increased with development and reached the adult level by 20 days after birth. Heparan sulfate (HS) was the major sulfated GAG in the fetal rat brain at early developmental stages, but HS accounted for approximately 10% of the total GAG in the postnatal brains. In addition to these GAGs, a polysialosyl glycoconjugate was isolated from rapidly growing brains of the rat. These three GAGs could be isolated either from the cerebellum, cerebrum, or brainstem of the newborn rat. A closely similar age-related change in the GAG composition was observed in each of these different regions of the brain. The developmental change could be implicated in morphogenesis or maturation of the brain. PMID- 3090204 TI - Inhibition of monoamine oxidase by 3,4-dihydroxyphenylserine. AB - The effects of diastereomers of 3,4-dihydroxyphenylserine (DOPS) on the enzyme activity of monoamine oxidase (MAO) in human placenta and liver mitochondria were examined. Both L- and D-threo-DOPS were found to inhibit MAO-A in human placental mitochondria in competition with the substrate, and the Ki values for L- and D threo-DOPS obtained were 68.3 and 125 microM, respectively. The inhibitory effect of L-threo-DOPS on both MAO-A and -B activity was confirmed in human liver mitochondria, and MAO-A was found to be more sensitive to the inhibitor. Other isomers of DOPS, L- and D-erythro-DOPS, were found to inhibit MAO activity, but the inhibition was noncompetitive with the substrate. The inhibitory effects of DOPS isomers were not affected by the presence of NSD-1055, an inhibitor of aromatic L-amino acid decarboxylase, suggesting that the inhibition is the direct effect of DOPS, and not of norepinephrine produced by the decarboxylase. PMID- 3090205 TI - Effect of altered blood plasma osmolalities on regional brain amino acid concentrations and focal seizure susceptibility in the rat. AB - Blood plasma hypo- or hyperosmolality alters significantly the concentration of some amino acids in brain tissues of the medial septum and hippocampus of adult Sprague-Dawley rats. With some notable exceptions, brain amino acid concentrations decreased under hypoosmotic conditions and increased under hyperosmotic conditions. Osmotic changes and brain amino acid changes appear to be related to each other in an almost linear fashion. A comparison of rats and toads indicates that the patterns of changes in brain amino acid concentrations in response to a hypoosmotic plasma osmolality were almost identical for both species. Changes achievable under hyperosmotic conditions were considerably greater in toads. When rats with kindled epileptogenic foci were made hypoosmotic by water-loading, seizure thresholds decreased dramatically. Our data suggest a possible relationship between the hypoosmotically induced biochemical changes in brain tissues (especially some amino acid neurotransmitters and neurotransmitter precursors) and the hypoosmotically induced increase in seizure susceptibility. PMID- 3090206 TI - Extracellular fluid proteins of goldfish brain: evidence for the presence of proteases and esterases. AB - Preparations of enriched fractions of extracellular fluid (ECF) proteins from goldfish brain were found to contain protease(s) and esterase(s). The N substituted furanacryloyl (FA) peptides FA-Phe-Gly-Gly and FA-Phe-OMe were used as model substrates for determining protease and esterase activity, respectively, in a spectrophotometric assay. Studies of the profile of substrate specificity and identification of the types of compounds that were effective as inhibitors showed that these ECF enzymes have some distinctive properties. GSH, but not GSSG, and EDTA inhibited the protease(s) without influencing the esterase(s), whereas L-1-tosylamide-2-phenylethylchloromethyl ketone blocked both protease and esterase activities of ECF. Most of the protease and esterase properties of ECF could be bound to concanavalin A-Sepharose affinity chromatographic columns in association with ependymin--a brain extracellular protein. These observations indicate that ECF may contain a metalloprotease(s) and raise the possibility that the ependymins might be a substrate for these ECF enzymes. PMID- 3090207 TI - The effect on plasma prolactin levels of interictal epileptiform EEG activity. AB - Because of the known effects of seizures on plasma prolactin, the plasma prolactin levels were measured before and after generalised interictal epileptiform activity was provoked in the EEG in five epileptic patients. The findings were compared with those obtained in five normal subjects and three epileptic patients who were also exposed to flicker stimulation, but who did not develop a photoconvulsive EEG response. There was no significant difference in baseline prolactin values, and levels did not change with photic stimulation or in response to the presence of generalised epileptiform activity in the EEG. PMID- 3090208 TI - Phase I/II trial of human recombinant interferon gamma in renal cell carcinoma. AB - Recombinant interferon gamma (IFN-gamma) was given to 13 patients with metastatic renal cell carcinoma in a Phase I/II trial. Patients were treated twice weekly by a 4-h intravenous infusion. Three patients were each entered at escalating dose levels. Doses were also escalated in each patient until an individual maximum tolerated dose was reached. Pharmacokinetics, toxicity, and tumor response are reported. Blood levels were related to dose and were detected in 6/7 patients receiving 30-75 MU/m2. The t1/2 was approximately 60 min in the higher dose patients, although detectable serum levels in some patients were observed at 24 h. The maximum tolerated dose was 75 MU/m2. Toxicity was limited to the symptom complex of anorexia, fever, and malaise. The latter two were dose-related and quite severe in high-dose patients. No minor or partial responses were observed in any patient. PMID- 3090209 TI - In vitro restoration by interleukin-2 (IL-2) of the impaired natural killer cell activities, IL-2 receptor expression, and T cell proliferation in hemophilia. AB - Five of 22 hemophiliacs who were seropositive for human T cell leukemia virus III (HTLV III) and manifested severe impairment of immune parameters (both in vivo and in vitro) similar to those observed in patients with clinical symptoms of acquired immune deficiency syndrome (AIDS) were chosen for this study. Profound lymphopenia was observed in four of five patients with decreased and qualitatively impaired helper/inducer (T4) cells and increased T suppressor/cytotoxic (T8) cells. Observed in all patients was impaired endogenous production of interleukin-2 (IL-2), expression of the IL-2 receptor combined with diminished responses to mitogens, mixed leukocytes reaction (MLR), and natural killer (NK) reactivity. In vitro supplement of exogenous IL-2 markedly augmented T and NK cell functions, as well as the expression of activation antigens on both T4 and T8 cell in four of five patients. Our findings suggest that a substantial proportion of this cell-mediated immunologic defect in hemophiliacs stems from their inability to produce adequate amounts of IL-2. Interleukin-2 may therefore have the potential for therapy as an immune response modifier in patients with hemophilia by providing beneficial preventive therapy for patients at risk. PMID- 3090210 TI - Central nervous system toxicity following the treatment of pediatric patients with ifosfamide/mesna. AB - Ifosfamide/mesna treatment of 50 patients with pediatric malignant solid tumors was associated with the development of neurotoxic signs and symptoms in 11 of these individuals who received 29 courses of treatment. Neurologic toxicity included changes in mental status, cerebellar function, cranial nerve, and cerebellar and motor system function, including seizures. All symptoms, signs, and EEG abnormalities were transient. Some of the affected individuals failed to develop acute neurotoxic signs of symptoms when retreated with ifosfamide. A grading system for scoring these neurologic abnormalities is presented for comparison of acute neurotoxic effects of other agents. Recommendations are made regarding early termination or delay of ifosfamide/mesna treatments in the presence of significant neurotoxicity. PMID- 3090211 TI - A role of the central catecholamine neuron in cerebral circulation. AB - The effect of the central catecholaminergic neurons on the cerebral microcirculation was investigated by means of a unilateral intracerebral injection of 6-hydroxydopamine (6-OHDA) which produced the degeneration of catecholamine (CA) nerve terminals. Subsequent observation with CA histofluorescence revealed an absence of CA fibers in the vicinity of the 6-OHDA injection site. A significant increase in regional cerebral blood flow (rCBF), measured by the hydrogen clearance method, was demonstrated in the CA-depleted cortex under normocapnia as compared with rCBF in the control cortex (CA-depleted cortex 47.0 +/- 2.8 ml/100 gm/min; control cortex 38.5 +/- 3.5 ml/100 gm/min; p less than 0.005). The increased rCBF in the cortex treated with 6-OHDA was suppressed by the iontophoretic replacement of noradrenaline (NA) to the CA depleted cortex. An iontophoretic replacement of 10(-5) M dopamine (DA) mildly suppressed the increased rCBF in the 6-OHDA-treated cortex. The CO2 reactivity in the CA-depleted cortex was significantly lower than that of the control cortex (CA-depleted cortex 2.13% +/- 0.6%/mm Hg; control cortex 3.53% +/- 0.70%/mm Hg). No change was noticeable in the cerebral glucose metabolism in the CA-depleted cortex in an investigation based on tritiated (3H)-deoxyglucose uptake. It is suggested that the 6-OHDA-induced change in cerebral blood flow (CBF) is not secondary to alterations in cerebral metabolic rate, and that the central NA neuron system innervating intraparenchymal blood vessels regulates CBF through a direct vasoconstrictive effect on the cerebral blood vessels. The central DA neuron system may modulate the cerebral circulation as a mild vasoconstrictor. PMID- 3090212 TI - Palatal swellings associated with multilesional disorders: report of cases. AB - Two cases with similar initial oral manifestations, i.e., solitary, unilateral soft tissue palatal swellings, were presented. These two cases represented separate and distinct conditions, multiple lipomas and neurofibromatosis. These conditions were reviewed briefly, together with tuberous sclerosis, as conditions in which both oral and multiple cutaneous nodules may be present. PMID- 3090213 TI - Age-related changes in the kinetics of release of proteoglycans from normal rabbit cartilage explants. AB - The release of proteoglycans from explant cultures of articular cartilage from immature and mature rabbits has been studied with the following results. At both ages the tissue proteoglycan was released in two phases: an initial extensive release (day 0 to 3) and a period of slow release (day 4 to 15). The percentage released in the initial phase was, however, significantly greater for mature (55%) than immature (38%) explants. At both ages the newly synthesized proteoglycans (in vivo labeled) were also released in two kinetic pools. Thus, graphical analysis of release data readily resolved the disappearance curves into two linear components with in vitro half-lives of 1 day and 22 days. Again, the percentage in the short half-life pool was much greater for mature (70%) than immature (40%) explants. At both ages the initial release was largely chondrocyte mediated since freeze-thawing the tissue before culture markedly reduced proteoglycan release. At both ages the released proteoglycans were smaller than equivalent preparations of extracted proteoglycans and they were much less capable of forming aggregates with hyaluronate. The results show that there are age-dependent changes in rabbit articular cartilage that increase the proportion of proteoglycans, both total and newly synthesized, that are susceptible to rapid chondrocyte-mediated catabolism in explant cultures. PMID- 3090214 TI - Investigation of factor VIII related antigen in peripheral giant cell granuloma. PMID- 3090215 TI - The structural brain mutant Vacuolar medulla of Drosophila melanogaster with specific behavioral defects and cell degeneration in the adult. AB - The mutant Vam (Vacuolar medulla) has vacuoles in the distal medulla, caused by age-dependent cell degeneration in the lamina and the medulla. Lamina monopolar neurons L1 and L2 degenerate, but whether the degeneration is confined only to these cells is uncertain. The cell degeneration commences at eclosion and the vacuoles begin appearing about 1/2 h after eclosion. This is accompanied by the disappearance of the electroretinogram transients and a loss of the optomotor response. Vam males or homozygous Vam females one day after eclosion or later, show no measurable optomotor response to horizontal or vertical movement and no landing response. However, they are able to turn towards dark stripes larger than 20 degrees in width. This indicates that motion-dependent visual responses are not a prerequisite for landmark fixation in Drosophila. The mutant's apparent defects suggest that the loss of motion-dependent visual functions is due to the loss of certain cell types linking the lamina to the distal medulla. The role of lamina neurons in optomotor responses and fixation behavior is discussed. PMID- 3090216 TI - Enteral versus parenteral therapy for intractable diarrhea of infancy: a prospective, randomized trial. AB - Thirteen infants with intractable diarrhea were classified as having severe or moderate malabsorption on the basis of D-xylose absorption. Within each group (designated severe and moderate), patients were randomly assigned to continuous enteral nutrition (CEN) with an elemental formula or to an alternative therapy: total parenteral nutrition (TPN) for the severe patients or intermittent oral nutrition (ION) with the elemental formula for the moderate patients. Within the severe group, CEN and TPN produced similar correction of malnutrition (6.0 +/- 2.5 weeks vs 6.5 +/- 2.5 weeks for weight to reach the 5th percentile for age, P = 0.69), but CEN was associated with faster resolution of malabsorption and diarrhea (2.8 +/- 0.5 weeks vs 9.8 +/- 1.1 weeks, P = 0.02), fewer complications, and less expensive hospitalization than TPN. The moderate group was too small for clear distinctions between the two therapies. D-xylose absorption effectively distinguished between severe malabsorption (requiring 20.6 +/- 2.6 days of enteral therapy before tolerance of oral feeding) and moderate malabsorption (requiring 11.6 +/- 1.7 days), P less than 0.03. Enteral therapy is more widely applicable in severe intractable diarrhea of infancy than has been appreciated, and can produce superior results to TPN. PMID- 3090217 TI - Neonatal effects of transplacental exposure to PCBs and DDE. AB - Neonatal effects of transplacental exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) were examined in a study of 912 infants. Birth weight, head circumference, and neonatal jaundice showed no relationship to PCBs or DDE. We also administered the Brazelton Neonatal Behavioral Assessment Scales, which are psychologic and neurologic tests designed for use in newborn infants. The results of these tests showed that higher PCB levels were associated with hypotonicity and hyporeflexia and that higher DDE levels were associated with hyporeflexia. PMID- 3090218 TI - Autoimmunity in Chagas' disease. PMID- 3090219 TI - Intestinal mast cell polymorphism: new research directions and clinical implications. PMID- 3090221 TI - Retinol-binding protein and prealbumin: useful measures of protein repletion in critically ill, malnourished infants. AB - Plasma prealbumin (PA) and retinol-binding protein (RBP) concentrations were serially measured in 25 critically ill, malnourished infants requiring parenteral nutrition to determine if these visceral protein markers are useful in assessing acute protein repletion. Significant increases in both proteins (p less than 0.05) were noted as early as 5 to 7 days after institution of parenteral nutrition and continued significantly above baseline values through 2 weeks of observation. Gestational development (in infants less than 4 weeks old) and mean protein intake influenced visceral protein responses. Appropriate for gestational age neonates had more rapid and quantitatively greater PA responses (p less than 0.05) than small for gestational age neonates. Small for gestational age neonates never exceeded baseline RBP responses. Average protein intake of less than or equal to 2 g/kg/day resulted in PA and RBP concentrations below baseline and significantly lower than infants on higher protein intakes (p less than 0.05), at the end of 2 weeks. Average calorie intake of greater than 100 cal/kg/day had no differential influence on PA or RBP when compared with infants on less calories. Prealbumin values correlated with RBP values observed simultaneously (r = 0.588, p less than 0.0001). We conclude that PA and RBP are useful measures of protein repletion in critically ill infants requiring parenteral nutrition. PMID- 3090220 TI - Comparison of fatty acid composition of plasma lipid fractions in well-nourished Nigerian and German infants and toddlers. AB - The dietary intake of essential fatty acids is reflected by the plasma lipid composition. Only scanty data is available on the pattern of plasma fatty acids in young children and the influence of different environments. We analyzed the fatty acid composition of plasma sterolesters, triglycerides, and phospholipids in well-nourished-appearing children from Benin City, Nigeria (n = 8; aged 14.1 +/- 7.2 months) and Dusseldorf, FRG (n = 17; aged 15.2 +/- 5.1 months). The Nigerian group tended to have bigger proportions of the essential omega-6-fatty acids, linoleic acid, and its metabolites, and by far higher values for long chain omega-3-fatty acids, which are considered to be protective against atherogenesis. The saturated and nonessential monoenoic fatty acids tended to be lower in the Nigerian children, and the ratio of polyunsaturated to saturated fatty acids was higher. We conclude that the quality of dietary fat in the German children was worse and may imply an increased risk for development of atherosclerosis. PMID- 3090222 TI - Budd-Chiari syndrome in a premature infant receiving total parenteral nutrition. AB - A premature infant who developed Budd-Chiari syndrome as a complication of total parenteral nutrition through an inferior vena cava catheter is presented. A novel approach to the treatment of this otherwise lethal condition is described. This very unusual complication in pediatric patients may be seen with increased frequency as more premature infants are treated with central vein total parenteral nutrition. PMID- 3090223 TI - Carnitine and lipid emulsion metabolism in premature infants. PMID- 3090225 TI - Experience with esophageal stenting for caustic burns in children. AB - Seven children with deep circumferential esophageal burns were treated with antibiotics, steroids, and intraluminal silastic stents. Strictures did not develop if the esophagus was healed at the time the stent was removed. However, strictures developed if healing was incomplete. Esophageal stenting needs to be continued until healing has been demonstrated endoscopically. PMID- 3090224 TI - Gastroesophageal reflux and the premature infant. AB - Gastroesophageal reflux (GER) is a well-recognized problem in infants and children. Only scant mention of the premature infant with GER can be found in the literature. Of 760 preterm infants admitted to the NICU between 1980 and 1984, 22 had documented GER. These infants all underwent medical management including upright positioning, small frequent feeds, and often, nasojejunal feedings. Seventeen babies did not respond to medical management and underwent surgical therapy to control the reflux. Of the 17 babies requiring fundoplication, 15 had been initially intubated for treatment of respiratory distress syndrome. Eight of these 15 were extubated in less than 25 days and were improving until they exhibited sudden episodes of deteriorating pulmonary status requiring reintubation. The other seven intubated patients developed striking bronchopulmonary dysplasia (BPD) in the first month and required prolonged ventilatory support. Pulmonary deterioration, failure to grow, and refusal to eat became the herald of GER in these infants. Fundoplication dramatically improved the pulmonary status in all but one infant. Three late deaths can be attributed to cor pulmonale and pulmonary failure. BPD was striking predisposing factor for severe GER in these premature infants. In the total premature population without BDP only 8 of 684 (1.2%) had GER with five responding to medical management and three others undergoing fundoplication for apnea-bradycardia spells. Fourteen of the 76 infants with BPD (18.4%) had significant GER and all required surgical management for control of symptoms. Premature infants who develop deteriorating pulmonary function, poor growth, and/or refusal to eat should be evaluated for GER. PMID- 3090226 TI - Discharge planning for children with perforated appendicitis. AB - Optimal management of children with perforated appendicitis remains a controversial clinical problem. Until very recently, the criteria for hospital discharge on our surgical service included the absence of fever and leukocytosis for a period of 48 hours following completion of antimicrobial therapy, uncomplicated wound healing, a normal rectal examination, and unimpaired gastrointestinal function. With the introduction of cost-containment programs, the necessity for the period of inpatient observation following cessation of antibiotics was questioned. The records of 87 consecutive children with perforated appendicitis were analyzed prospectively in order to determine if our discharge policies were medically sound and cost-effective. Seventy-five patients (86%) recovered uneventfully while 12 children required prolonged hospitalization for management of various postoperative complications. The 12 patients who developed complications were all identifiable early in the postoperative period because of persistent fever, leukocytosis, and elevated band counts. Of the 75 children who recovered uneventfully, all met standard discharge criteria on the final day of antibiotic therapy with the exception of completing the mandatory 48 hour period of inpatient observation. These children were maintained in the hospital a total of 142 additional days following discontinuation of antibiotics. The average cost per patient day for children with perforated appendicitis during the study period was $506.32, which represented unnecessary hospital charges of $71,897.44. It was concluded that inpatient observation following cessation of antibiotic therapy in children who experience an uneventful recovery from perforated appendicitis is neither necessary nor cost-effective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090227 TI - Effect of AD-1590, a non-steroidal anti-inflammatory agent with a potent antipyretic activity, on in vitro prostaglandin generation in rabbit brain. AB - The inhibitory activity of 2-(8-methyl-10,11-dihydro-11-oxodibenz[b,f]oxepin-2 yl) propionic acid (AD-1590) against prostaglandin (PG) generation in the rabbit brain was compared with that of indomethacin in vitro. AD-1590 inhibited PGE2 generation by hypothalamus microsomes at concentrations of 0.1 micrograms/ml or more, its IC50 value being 0.258 micrograms/ml. On the other hand, PGE2 generation by cerebral cortex slices was suppressed by about 10 times lower concentrations of AD-1590 in comparison with that by hypothalamus microsomes; its IC50 value was 0.0292 micrograms/ml. The potency of AD-1590 was 3.4 and 2.6 times that of indomethacin in the hypothalamus microsomes and cerebral cortex slices, respectively. The inhibitory activity of AD-1590 against PGE2 generation by hypothalamus microsomes was similar to the result with renal medulla microsomes; the ratio of renal medulla to hypothalamus IC50 values of AD-1590 (0.496) was nearly equal to that of indomethacin (0.384) and aspirin (0.452). The present studies confirmed that AD-1590 inhibited PGE2 generation within the hypothalamic region. However, these results suggest that the inhibitory potency of AD-1590 against brain PG synthetase cannot explain the 20-50 times more potent antipyretic activity than that of indomethacin, previously reported. The mode of potent antipyretic action of AD-1590 is discussed. PMID- 3090228 TI - Suppressive effect of interferon inducer, polyriboinosinic acid-polyribocytidylic acid on induction of uridine diphosphate-glucuronyltransferases and monooxygenases in liver microsomes of rats. AB - The effect of polyriboinosinic acid-polyribocytidylic acid [poly(I).poly(C)] on glucuronyltransferase activities toward 4-nitrophenol and 4-hydroxybiphenyl in liver microsomes of Wistar rats was examined by its single or co-administration with 3-methylcholanthrene and phenobarbital. The increased 4-nitrophenol glucuronyltransferase activity by treatment with 3-methylcholanthrene was significantly suppressed following the co-administration with poly(I).poly(C), although the activity was not affected by the treatment with poly(I).poly(C) alone. In addition, 4-hydroxybiphenyl glucuronyltransferase activity decreased or tended to decrease by the treatment with poly(I).poly(C) alone, and the activity induced by phenobarbital was strikingly decreased following the co-administration with poly(I).poly(C). This result suggested that poly(I).poly(C) comprehensively decrease the induction of glucuronyltransferases regardless of their multiple forms. Furthermore, contents of cytochromes P-450 and b5 were also decreased by the treatment with poly(I).poly(C) alone or the co-administration with the inducers. Concomitantly, arylhydrocarbon hydroxylase and benzphetamine N demethylase activities were significantly decreased by the treatment alone or the co-administration with the inducers. These findings supported a view that the suppressive effect of poly(I).poly(C) may be derived from the prevention of de novo synthesis of the apoprotein of the enzymes and/or the increased degradation. PMID- 3090229 TI - To feed or not to feed: that is the question and the ethical dilemma. PMID- 3090230 TI - Expression of the Proteus mirabilis recA gene in Bacillus subtilis is directed by its own promoter. AB - The recA gene of Proteus mirabilis (recApm) has been cloned into the PstI site of the Bacillus promoter-probe plasmid pPL603. When present on this plasmid, the recApm1) gene is expressed in B. subtilis under the control of its own transcriptional and translational signals. It is concluded that the high AT content of the DNA sequence upstream of the -35 region is of decisive importance for the usage of the recApm promoter by the B. subtilis RNA polymerase. The results are discussed in relation to the expression barriers found to exist for genes from gram-negative bacteria in the gram-positive B. subtilis. PMID- 3090231 TI - Expression of the streptokinase gene from Streptococcus equisimilis in Bacillus subtilis. AB - The previously cloned and sequenced streptokinase gene (skc) from Streptococcus equisimilis H46A was inserted into plasmid vectors capable of replication in Bacillus subtilis. The skc gene was expressed by use of its own transcription and translation signals which appeared to meet the stringent requirements of B. subtilis for efficient foreign gene expression. The secreted streptokinase activity began to decline toward the end of the exponential growth phase suggesting that B. subtilis exoproteases hydrolyzed and inactivated the foreign protein. PMID- 3090232 TI - Nonlinear estimation of kinetic parameters for solid-state hydrolysis of water soluble drugs. AB - Nonlinear-regression analysis was applied to estimate the kinetic parameters for the solid-state hydrolysis of meclofenoxate hydrochloride [2-(dimethylamino)ethyl (4-chlorophenoxy)acetate hydrochloride; 1] and propantheline bromide [(2 hydroxyethyl)diisopropylmethylammonium bromide xanthene-9-carboxylate; 2]. The percent decomposed (x) at the initial stage of decomposition was found to conform to the empirical equation x = ktn, where n and k are constants. The goodness of fit of the data was better than with the Prout-Tompkins equation. The parameters indicating the dependence of the rate on temperature (T) and water vapor pressure (P) were estimated by nonlinear-regression analysis based on the equation: x = x0 exp[(Ea/R)(1/298-1/T)] (P/18.167)s(t/50)n, where xo is the percent decomposed at t = 50 d, T = 298 K and P = 18.167 mmHg, and Ea (activation energy), s, and n are constants. For the hydrolysis at a relative humidity (RH) above the critical relative humidity (CRH), nonlinear parameter estimation provided statistically meaningful estimates of Ea, s, x0, and n, and it was suggested that these parameters could be regarded as constants in the experimental range. For the hydrolysis at RH below the CRH, however, the parameters could not be converged by nonlinear-regression analysis, and Ea and/or s were assumed not to be constant in this RH range. PMID- 3090233 TI - Surgically soft eye for cataract removal. PMID- 3090234 TI - Mechanism of action and structural requirements of vasopressin analog inhibition of transepithelial water flux in toad urinary bladder. AB - Vasopressin, vasopressin analogs, forskolin and 8-bromo-cyclic AMP (8Br-cAMP) were studied for their effects on transepithelial water flux in toad urinary bladder. Arginine vasopressin, arginine vasotocin, oxytocin, desamino-8-D arginine vasopressin, forskolin and 8Br-cAMP stimulated hydro-osmotic water flux in a dose-dependent fashion. The rank order of potency was arginine vasotocin greater than arginine vasopressin greater than oxytocin greater than desamino-8-D arginine vasopressin greater than forskolin greater than 8Br-cAMP. The vasopressin analogs [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine,8-arginine]vasopressin (SK&F 100273), [1-(beta mercapto-beta,beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine,4 valine,8-arginine]vasopressin (SK&F 100501), [1-(beta-mercapto-beta,beta cyclopentamethylene propionic acid),2-D-tyrosine,4-valine,8-arginine]vasopressin (SK&F 100885), [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid),2 (O-ethyl)tyrosine,4-valine,8-arginine]vasopressin (SK&F 100398), [1-(beta mercapto-beta,beta-cyclopentamethylene propionic acid),2-D-isoleucine,4-valine,8 arginine]vasopressin (SK&F 101485), [1-(beta-mercapto-beta,beta cyclopentamethylene propionic acid),2-(O-ethyl)-tyrosine,4-valine,8 arginine]vasopressin (SK&F 101498), [1-(beta-mercapto-beta,beta cyclopentamethylene propionic acid),2-(O-ethyl)D-tyrosine,4-valine,8-arginine,9 desglycine]vasop ressin (SK&F 101926) and [1-(beta-mercapto-beta-beta cyclopentamethylene propionic acid),2-D-phenylalanine,4-valine,8-arginine] vasopressin (SK&F 101071) antagonized arginine vasopressin-stimulated water flux and displaced the agonist dose-response relationship to the right in a parallel fashion. The most potent antagonists were those having the (O-ethyl)-D-tyrosine substitution at position 2. None of the antagonists tested had any effect on 8Br cAMP-stimulated water flux at concentrations up to 10(-6)M.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090235 TI - Bumetanide inhibition of [CO2 + HCO3]-dependent and -independent equivalent electrical flux in renal cortical thick ascending limbs. AB - Experiments were performed on single perfused segments of cortical thick ascending limbs of Henle isolated from mouse kidney in order to evaluate the interaction of bumetanide with apical membrane [CO2 + HCO3]-dependent and independent sodium uptake. In this nephron segment [CO2 + HCO3]-dependent apical membrane salt uptake is accomplished by parallel Na+/H+ and Cl-/HCO3- exchange whereas [CO2 + HCO3]-independent salt uptake results from NaCl cotransport. Tubules were perfused and bathed at 37 degrees C in either [CO2 + HCO3]-buffered solutions (KRB) or with 4-(2-hydroxy(ethyl)-1-piperazineethanesulfonic acid buffered external media (KRH) at pH 7.4. The spontaneous transepithelial voltage was measured through one-half of a double-barreled perfusion pipette and bipolar d.c. current pulses were delivered through the other half in order to measure the transepithelial conductance (milliSiemens per squared centimeter). The rate of net NaCl absorption was estimated from the electrical flux (Je) and was calculated from the equivalent short-circuit current. Cumulative dose-response data over the range 10(-7) to 10(-4) M luminal bumetanide were obtained in individual tubules in both KRB and KRH solutions. Significant inhibition of transepithelial voltage and Je obtained at 5 X 10(-7) M bumetanide (in KRB) to 10(-6) M (in KRH). When the effect of [CO2 + HCO3] per se on Je was subtracted from the bumetanide-induced inhibition, the two dose-response curves converge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090236 TI - Effects of detergents on sodium transport in toad urinary bladder. AB - The effects of ionic, nonionic and zwitterionic detergents (zwittergents) on apical sodium permeability of toad urinary bladder were investigated. Applied to the mucosal side at concentrations less than 1/100 of their respective critical micellar concentration (CMC), sodium lauryl sulfate, Triton X-100 and a series of sulfobetaine zwittergents reversibly increased amiloride-sensitive sodium current. These detergents decreased the current at concentrations higher than 1/100 of the CMC and caused large, irreversible increases of tissue electrical conductance at a concentration close to the CMC. Nonionic detergent Tween 80, however, stimulated the current at concentrations from 1/100 to 10,000 of its CMC. The maximum stimulation of current by each zwittergent occurred at 1/100 of its CMC, and the larger the CMC, the greater the stimulation attainable. Analysis of the dependence of current on mucosal sodium concentration in the presence of stimulating doses of a zwittergent and Tween 80 showed that the increase in current was not the result of increased apical maximum sodium permeability, but the consequence of removal of sodium self-inhibition. The amiloride dose-response curve in the presence of stimulating dose of zwittergent was shown to shift to the left and yield a smaller apparent inhibition constant as predicted on the basis of such a removal and an unaltered intrinsic amiloride blocking kinetic. PMID- 3090237 TI - Modulation of the behavioral effects of anticonvulsant drugs by an external discriminative stimulus in the pigeon. AB - The effects of the anticonvulsant drugs valproic acid, phenytoin, phenobarbital and diazepam were examined in pigeons performing under a fixed-consecutive-number schedule with and without an added external discriminative stimulus. Under these schedules, a reinforced response run consisted of responding between eight and 12 times on one response key (work key) and then responding once on a second response key (reinforced key). For one group of pigeons, an external discriminative stimulus signaled completion of the response requirement on the work key, whereas no stimulus change was programmed for the other group. Phenobarbital (5-60 mg/kg) and diazepam (0.5-6 mg/kg) produced large decreases in reinforced response runs (accuracy) and rates of responding. The magnitude of these accuracy- and rate-decreasing effects was larger in the group without the external discriminative stimulus. Under both schedules, these drugs produced pronounced increases in the probability of switching to the reinforcement key before completion of the minimal response requirement on the work key. Valproic acid (20-160 mg/kg) and phenytoin (1.25-10 mg/kg) also decreased both accuracy and rates of responding. Although the accuracy-decreasing effects of these drugs were relatively small in magnitude, they were consistently larger in the group without the external discriminative stimulus. These data suggest that the addition of an external discriminative stimulus attenuates the disruptive behavioral effects of anticonvulsant drugs. PMID- 3090238 TI - Leishmania mexicana pifanoi: analysis of the antigenic relationships between promastigotes and amastigotes by gel diffusion, immunoelectrophoresis, and immunoprecipitation. AB - The antigenic relationships between Leishmania mexicana pifanoi promastigotes, axenically grown amastigotes, and amastigotes isolated from the footpads of infected hamsters or from a J774 macrophage cell line were studied by three serologic methods. Amastigote and promastigote antigens were disrupted by freeze thawing of intact cells in a lysis buffer. Antisera were prepared in rabbits by repeated subcutaneous inoculations of the parasite antigens in complete Freund's adjuvant and were tested against the homologous and heterologous antigens in a series of gel diffusion experiments. Negative results were obtained in all control experiments. In each instance, the homologous antigen-antiserum reactions yielded the largest numbers of precipitin lines. A pattern of cross-reactivity was also observed in the heterologous systems. Results indicated that the amastigote and promastigote forms had unique and common antigens. The two parasite antigen-antiserum systems were also examined by immunoelectrophoresis. Qualitative and quantitative differences between the promastigote and amastigote antigens were readily demonstrable by this technique. Results indicated that each parasite form had specific and many common antigens. In the homologous system, major proteins, with molecular weights (MW) of 23, 52, and 68 kd, were demonstrated in the promastigotes by immunoprecipitation of lactoperoxidase catalyzed radioiodinated cells. In a similar (homologous) system, axenically grown amastigotes were found to contain three proteins with MW of 38, 70, and 74 kd and, therefore, different from those demonstrated for the promastigotes. All the results suggested that the three amastigote stages of different origins are antigenically similar to one another, but differ from the promastigote forms. PMID- 3090239 TI - Observations on the Taiwanese strain of Leucocytozoon caulleryi (Haemosporina) in chickens. AB - The Taiwanese strain of Leucocytozoon caulleryi was isolated from an infected chicken in Taipei, Taiwan, and established in chickens and biting midges Culicoides arakawae from Japan. Sporogony of the strain in C. arakawae was completed on day 3 after the infective blood meals at 25 degrees C. Sporozoites isolated from the salivary glands of C. arakawae on days 3 or 4 after feeding caused infection in all the chickens inoculated. The strain showed high pathogenicity for chickens. Mortality of chickens rose with an increase in the number of sporozoites inoculated. The prepatent period for chickens inoculated with sporozoites was 14 days. Parasites appeared in the peripheral blood of chickens on day 15 and disappeared on day 26 after sporozoite inoculation. Soluble antigens were found in the sera of chickens infected with the strain between 10 and 17 days after inoculation, and homologous antibodies appeared after 17 days. Antigens prepared from sera, schizonts, merozoites, and gametocytes of the Taiwanese strain reacted with the sera of chickens infected with the same strain or the strain isolated in Japan. The chickens that recovered from a primary infection with the Taiwanese strain demonstrated complete resistance to reinfection with the same strain or the the strain isolated in Japan. PMID- 3090240 TI - Polyamine depletion following exposure to DL-alpha-difluoromethylornithine both in vivo and in vitro initiates morphological alterations and mitochondrial activation in a monomorphic strain of Trypanosoma brucei brucei. AB - DL-alpha-difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase (ODC), rapidly depletes cells of intracellular putrescine. When administered to animals and humans, DFMO cures acute infections of trypanosomiasis. In order to determine if the mechanism of drug action is related to initiation of transformation and biochemical alterations subsequent to polyamine depletion, trypanosome morphology and mitochondrial activation were studied in a monomorphic strain of Trypanosoma brucei brucei. Exposure of trypanosomes to DFMO in vivo in infected rodents or in vitro in culture resulted in a depletion of intracellular putrescine and a cessation of cell division without specific cytotoxicity. These events were followed by a transformation of the long slender bloodstream form to a short stumpy form via an intermediate morphology. Putrescine, the product of the ODC reaction, abrogates this effect. When introduced into SDM-79 medium, the intermediate form is capable of further transformation to an "insect" procyclic trypomastigote whereas the long slender form and short stumpy form are not. Short stumpy forms are incapable of binary fission and have lost their infectivity for the vertebrate host. In addition, the mitochondrial marker enzyme, NAD diaphorase, was found only in the short stumpy and intermediate forms. We hypothesize that the short stumpy phenotype may not be a viable stage in the natural transformation of the trypanosome from its mammalian host to the insect vector. PMID- 3090241 TI - CO2 sensitive receptors on labial palps of Rhodogastria moths (Lepidoptera: Arctiidae): physiology, fine structure and central projection. AB - The tips of the labial palps of Rhodogastria possess a pit housing uniform sensilla, histologically characterized by wall-pores and receptor cells with lamellated outer dendrites. The receptor cell axons project to glomeruli in the deutocerebrum which are not innervated by antennal receptors. From their histology as well as from their central projection these sense organs are identical with palpal pit organs of other Lepidoptera (Lee et al. 1985; Kent et al. 1986; Lee and Altner 1986). Physiologically, the palp-pit receptors respond uniformly; they are most excitable by stimulation with carbon dioxide while they exhibit relatively moderate responses to various odorants. The responses to CO2 show a steep dose-response characteristic. In ambient atmosphere (i.e., ca. 0.03% CO2) the cells are in an excited condition already; the seeming 'spontaneous activity' exhibited in air is decreased if the preparation is kept under N2 or O2 or CO2-free air. There is hardly any adaptation of the responses to continuous or repeated stimulation. Perhaps CO2 sensitivity is correlated with sensilla characterized by both wall-pores and lamellated dendrites. Pilot tests indicate that CO2 perception might be widespread in the Lepidoptera, but the biological significance remains obscure. PMID- 3090242 TI - Domiciliary consultation--who benefits? AB - A survey was conducted of the domiciliary consultation service provided in one health district in order to identify the pattern of referral by specialty, the reasons for the consultation and its outcome and to determine whether the service is realizing its original objectives.The district domiciliary consultation service was used in the majority of cases as an initial means of assessment for elderly patients with chronic disease. The majority of patients were kept out of hospital but responsibility for their care was usually transferred to the consultant. The domiciliary consultation service was rarely used as a means for joint consultation between family doctor and hospital specialist. To facilitate the care of patients in the community, it is suggested that domiciliary visiting should be incorporated into a consultant's NHS contract and the present regulations abandoned. PMID- 3090243 TI - Photoperiodic regulation of seasonal testicular regression in the wild European rabbit (Oryctolagus cuniculus). AB - Adult male wild rabbits were exposed to artificial daylengths of 8L:16D, 13L:11D or 20L:4D after being taken from the wild during September, when testicular size was minimal. In all groups the testes grew and those in 20L:4D grew more quickly than did those in 8L:16D or 13L:11D. Rabbits kept in the 3 daylength treatments for the whole study maintained enlarged testes after the initial growth phase. The testes of rabbits transferred to 13L:11D after 8 weeks in 20L:4D did not regress. A similar transfer after 16 weeks in 20L:4D resulted in testicular regression (P less than 0.01) followed by moult, and then testicular regrowth 9 weeks after the change of daylength. No regression occurred at this time in the control group kept in 20L:4D throughout the study. Plasma FSH concentration increased at the beginning of the study and was elevated during the initial period of testicular growth. Values then declined after the asymptote of testicular weight was reached. Plasma testosterone and LH concentrations did not change significantly throughout the study. The results showed that reproductive regression in wild rabbits can be induced by a reduction in the daylength, but that the potency of this reduction is dependent upon previous experience of daylength. PMID- 3090244 TI - 125I-labelled hCG binding characteristics in theca interna and other tissues from Romney ewes and from Booroola x Romney ewes with and without a major gene influencing their ovulation rate. AB - Specific receptors for 125I-labelled hCG in ovarian follicle wall were located in the theca interna. No specific binding of 125I-labelled hCG was found in theca externa and/or stromal tissue. The kinetics of 125I-labelled hCG binding to theca interna followed second order kinetics with calculated association rate constants (ka +/- s.d.) of 1.57 +/- 0.16 X 10(6) and 0.57 +/- 0.02 X 10(6) litres mol-1 sec 1 at 37 degrees C and 22 degrees C respectively. Dissociation of specifically bound 125I-labelled hCG from theca interna was minimal at 37 degrees C and 22 degrees C. The binding of 125I-labelled hCG to theca interna could be displaced with PMSG, FSH-P and sheep LH but other sheep pituitary hormones and LH-releasing hormone showed little or no cross-reaction. The calculated binding capacities (Bmax) and equilibrium dissociation constants (Kd) for 125I-labelled hCG binding to theca interna did not differ between Romney ewes and Booroola x Romney ewes with and without the fecundity (F) gene on Day 10 of the oestrous cycle, during anoestrus or at 36 h after an injection of cloprostenol on Day 10 of the oestrous cycle. When the data for Day 10 and anoestrus were pooled, the median (range) Bmax and Kd values in non-atretic follicles (greater than or equal to 3 mm diameter) were 12.0 (5.1-23.5) fmol/mg protein and 0.10 (0.05-0.16) nM respectively. At 36 h after cloprostenol injection the respective median (range) Bmax and Kd values in non-atretic follicles (greater than or equal to 3 mm diam.) increased to 46.9 (28.4-70.3) fmol/mg protein and 0.23 (0.13-0.65) nM respectively. In corpora lutea the hCG binding characteristics were similar in all the above breeds/genotypes. On Day 10 of the cycle, the mean Bmax but not the mean Kd value was significantly higher (P less than 0.01) than the corresponding value at 36 h after cloprostenol injection. In granulosa cells, from follicles of greater than or equal to 5 mm diameter of Romney and Booroola x Romney (++) ewes and from follicles of greater than or equal to 3 mm diameter of Booroola x Romney (F+) ewes, the hCG binding characteristics were similar. In granulosa cells from smaller sized follicles from the above breeds/genotypes, no specific hCG binding was noted. PMID- 3090245 TI - Effects of ovine follicular fluid on plasma LH and FSH secretion in ovariectomized ewes to indicate the site of action of inhibin. AB - Ovariectomized ewes were given 2 ml s.c. injections of ovine follicular fluid (oFF) (N = 3) or serum (N = 3) and blood samples were collected each day for 3 days. Follicular fluid caused a significant (P less than 0.005) reduction in FSH within 1 day, but did not affect mean LH values. Two groups of 3 ewes were treated as above but sampled intensively (each 10 min for 6 h) on Days 1 (before treatment) and 4; mean plasma FSH concentration and plasma LH pulse frequency and amplitude were ascertained. Significant (P less than 0.005) reduction of FSH concentration was seen in the oFF-treated ewes. A non-specific reduction in LH pulse amplitude, but not pulse frequency, was noted in the control ewes. This experiment was repeated with 2 groups of 4 ewes that were conditioned to the experimental environment and effects on LH secretion were not observed in the controls given serum. Treatment with oFF caused a 70% reduction (P less than 0.005) in plasma FSH and a small (30%) but significant (P less than 0.005) reduction in mean LH concentrations. The latter was probably associated with a reduction in LH pulse amplitude in 3/4 animals (N.S.) with no change in LH pulse frequency. Treatment with oFF, as in Exp. 1, caused a 95% reduction in FSH values and significant (P less than 0.01) reduction (32%) of LH pulse amplitude in ovariectomized ewes that had been subjected to hypothalamo-pituitary disconnection and in which gonadotrophin secretion was reinstated with pulses of 250 ng GnRH every 2 h. These results suggest that proteins from the sheep follicular fluid, including inhibin, act at the pituitary level to inhibit FSH secretion and may have some effects on LH pulse amplitude. PMID- 3090246 TI - Blockade of pulsatile LH, FSH and testosterone secretion in rams by constant infusion of an LHRH agonist. AB - Adult Soay rams were infused for 21 days with 50 micrograms buserelin/day, using s.c. implanted osmotic mini-pumps. The continuous treatment with this LHRH agonist induced a supraphysiological increase in the blood concentrations of LH (15-fold) and testosterone (5-fold) followed by a decrease below pre-treatment values after 10 days. The blood concentrations of FSH showed only a minimal initial increase but the subsequent decrease was dramatic, occurring within 1 day. By Day 10 of treatment, the blood concentrations of all 3 hormones were low or declining, LH pulses were absent in the serial profiles based on 20-min blood samples and the administration of LHRH antiserum failed to affect the secretion of LH or testosterone. By Day 21, the secretion of FSH, LH and testosterone was maximally suppressed. The i.v. injection of 400 ng LHRH was totally ineffective at stimulating an increase in the blood concentrations of LH while the i.v. injection of 50 micrograms ovine LH induced a normal increase in the concentrations of testosterone; this confirmed that the chronic treatment with the LHRH agonist had desensitized the pituitary gonadotrophs without markedly affecting the responsiveness of the testicular Leydig cells. The ratio of bioactive: radioimmunoactive LH did not change during the treatment. The long term effect of the infusion was fully reversible as shown by the increase in the blood concentrations of FSH, LH and testosterone and the return of normal pulsatile fluctuations in LH and testosterone within 7 days of the end of treatment. PMID- 3090247 TI - Prolactin secretion in Sheehan's syndrome. Responses to thyrotropin-releasing hormone and metoclopramide. AB - The prolactin response to thyrotropin-releasing hormone (TRH) and metoclopramide was studied in 16 patients with Sheehan's syndrome and 16 matched controls in the follicular phase. Metoclopramide resulted in a greater prolactin response than TRH did in the controls. However, both stimuli failed to evoke any appreciable prolactin response in the patients with Sheehan's syndrome. Since metoclopramide is generally free of side effects and far cheaper than TRH, we recommend the prolactin response to metoclopramide as the preferred screening test in the diagnosis of Sheehan's syndrome. PMID- 3090249 TI - Some factors affecting the distribution of radon. PMID- 3090248 TI - Enhanced interleukin 1 and depressed interleukin 2 production in juvenile arthritis. AB - Blood mononuclear cells from a total of 23 children with juvenile arthritis were stimulated in vitro to produce interleukin 1 (IL-1) and interleukin 2 (IL-2) and compared with age matched healthy controls. Peripheral blood monocytes from patients with juvenile arthritis produced a higher amount of IL-1 than controls, whereas peripheral blood lymphocytes from the same patients produced lower amount of IL-2 than controls. These findings could not be explained by concurrent therapy. The increase of IL-1 production was more marked in patients with active disease and therefore may have been secondary to the pathological process. However, the decrease of IL-2 production did not depend on disease activity, thus suggesting an immunoregulatory abnormality. PMID- 3090251 TI - The Baragwanath Hospital in Soweto. PMID- 3090250 TI - Selected factors and stroke in young adults, 15-40 years of age. PMID- 3090252 TI - Brief exercise for diabetics. PMID- 3090253 TI - Goat's milk. PMID- 3090255 TI - Food irradiation. PMID- 3090256 TI - Methodology in practice--measuring height and weight in school populations. PMID- 3090254 TI - Contraceptive advice: how the English differ from the Americans. PMID- 3090257 TI - Education and food habits of Bahraini housewives. PMID- 3090258 TI - Drug hoarding in a Jerusalem community. PMID- 3090259 TI - Improving hearing aid benefit. PMID- 3090260 TI - Hearing aid dispensing in the private sector. PMID- 3090261 TI - Silent genital herpes simplex infection among asymptomatic female college students. PMID- 3090262 TI - Terrestrial gamma ray radiation in Cornwall. PMID- 3090263 TI - Ribose as the preferential target for the oxidized form of elliptinium acetate in ribonucleos(t)ides. Biological activities of the resulting adducts. AB - The covalent binding of the oxidized form of elliptinium acetate, an antitumor drug, to various ribonucleos(t)ides is described. In the absence of a strong nucleophile on the bases, e.g., a sulfhydryl group, the main target of this quinone imine derivative is the sugar moiety. With unmodified regular bases, the first electrophilic addition always occurs on the 2'-oxygen of ribose (more slowly for pyrimidine than for purine); in a second step, cyclization of the reoxidized product leads to a spiro derivative: only one stereoisomer is detected with purine nucleoside; the other stereoisomer appears as a minor product (10 20%) with nucleotides and pyrimidine nucleosides. With modified bases, no change is observed except for bases exhibiting an additional strong nucleophilic center: oxidized elliptinium alkylates thioguanine and thioguanosine on the sulfur atom and in this last case not on the ribose moiety. All spiro derivatives are less cytotoxic than the parent compound even if the base is an antimetabolite (azauridine); however, thio-elliptinium adducts maintain high cytotoxicity. PMID- 3090264 TI - Synthesis of [[(naphthalenylmethoxy)- and [[(quinolinylmethoxy)phenyl]amino]oxoalkanoic acid esters. A novel series of leukotriene D4 antagonists and 5-lipoxygenase inhibitors. AB - A series of novel [[(naphthalenylmethoxy)- and [[(quinolinylmethoxy)phenyl]amino]oxoalkanoic acid esters have been prepared. These compounds were tested as inhibitors of rat polymorphonuclear leukocyte (PMN) 5-lipoxygenase (LO) in vitro and as inhibitors of ovalbumin (OA) and leukotriene D4 (LTD4) induced bronchospasm in the guinea pig (GP) in vivo. Many naphthalenyl compounds were potent inhibitors of 5-LO, and several quinolinyl compounds were potent inhibitors of LTD4-mediated bronchospasms in the GP. The most potent naphthalenyl compound, 4-[[3-(2 naphthalenylmethoxy)phenyl]hydroxyamino]-4-oxobutanoic acid, methyl ester (6v), had an IC50 of 0.6 microM in the 5-LO assay. The most potent compound in vivo, 4 [[3-(2-quinolinylmethoxy)phenyl]hydroxyamino]-4-oxobutanoic acid, methyl ester (6e), had ED50's of 3.3 mg/kg and 27.4 mg/kg (intraduodenally) against LTD4- and OA-induced bronchospasm, respectively. When tested as an antagonist of LTD4 induced contraction of isolated GP tracheal spiral strips, 6e was shown to be a competitive inhibitor with a pKB value of 5.33. PMID- 3090265 TI - Synthesis and biological activity of benzothiazolo[3,2-a]quinolone antibacterial agents. AB - A new class of heterocyclic compounds with potent antibacterial activity, namely, 2-substituted amino-3-fluoro-5,12-dihydro-5-oxobenzothiazolo[3, 2-a]quinoline-6 carboxylic acids, is described. The compounds are conformationally restricted analogues of 7-substituted amino-6-fluoro-1-aryl-1, 4-dihydro-4-oxoquinoline-3 carboxylic acids. Compounds 7 and 10, having a 4-methylpiperazinyl and a piperazinyl substitution at the 2-position, respectively, possess in vitro antibacterial activities comparable to norfloxacin (15). Compound 8, which has a 4-acetylpiperazinyl substitution at the 2-position, is active against Gram positive organisms and nearly inactive against Gram-negative organisms. An efficient and short synthesis of this novel heterocyclic system via an intramolecular nucleophilic displacement cyclization reaction is reported. PMID- 3090266 TI - Transmission of Leucocytozoon smithi (Sporozoa: Leucocytozoidae) by black flies (Diptera: Simuliidae) in New York, USA. PMID- 3090267 TI - Rhodnius pallescens (Hemiptera: Reduviidae) in Costa Rica. PMID- 3090268 TI - Role of endotoxin in the pathogenicity of Neisseria gonorrhoeae colonial types 1, 4 and 5 determined by chicken embryo model. AB - The pathogenicity of Neisseria gonorrhoeae is a subject of considerable interest. It is believed that N. gonorrhoeae of colonial type 1 are pathogenic while those of type 4 are not. This is based on experimentation in human volunteers. The object of this study was to determine the reasons for the differences of susceptibility of chicken embryos to N. gonorrhoeae strains of colonial types 1, 4, 5 and 1R (a type-1 revertant from a non-pathogenic type 4 strain originally tested in human volunteers). Colonial types 1, 5, 1R and 4 caused mortality rates of 80, 70, 85 and 20% respectively. This variation in lethality appeared to depend upon the availability of free extra-cellular endotoxin and this was confirmed by chicken-embryo inoculation results and electronmicroscopy of normal and heated colonial types 1, 4 and 5. Similar results were obtained by inoculating purified endotoxins from these types into chicken embryos. The results of this study suggest that endotoxins play a major role in the pathogenicity of N. gonorrhoeae and that the variations in virulence of the colonial types depends on the stability of their cell walls. PMID- 3090269 TI - Effect of increase in macrophage Ia expression on subsequent immune response in vivo. AB - By the use of a culture supernatant containing a lymphokine capable of inducing Ia-rich peritoneal macrophages in vivo, we investigated the effect of increased macrophage Ia expression on the induction of antibody response to sheep erythrocytes (SRBC) in mice. Peritoneal macrophages from mice injected intraperitoneally (i.p.) with lymphokine 3 and 4 days earlier contained a high proportion of Ia-bearing macrophages without any significant increase in their phagocytic activity for SRBC. In lymphokine-treated mice, slight enhancement was observed in the primary IgG plaque-forming cell (PFC) response only at an early stage after i.p. immunization with SRBC. When primed mice were injected with lymphokine before secondary i.p. immunization with SRBC, the secondary IgG PFC response was greatly enhanced. On the other hand, lymphokine treatment did not affect either the primary or the secondary IgM PFC response. This effect was dependent on both timing of lymphokine injection and route of secondary immunization with SRBC. Secondary immunization via several routes other than the i.p. route never resulted in such an enhanced secondary IgG PFC response. These results suggest that lymphokine-induced Ia-rich peritoneal macrophages, which first encounter the antigen in the peritoneal cavity, play an important role in the modification of the subsequent antibody response. PMID- 3090270 TI - An ecdysterone-responsive puff site in Drosophila contains a cluster of seven differentially regulated genes. AB - We have determined the molecular organization of an ecdysterone-responsive puff site in Drosophila melanogaster. The 71E puff site contains a tightly linked cluster of at least seven genes within a neighborhood of 10 X 10(3) base-pairs. All the genes are expressed in a tissue-specific manner in either the larval or the prepupal salivary gland. However, these genes can be divided into two groups on the basis of their temporal pattern of transcription. Six of the genes are expressed only in prepupal salivary glands and are arranged as three divergently transcribed pairs. Nestled within this region is one gene expressed primarily in late third-instar salivary glands. We conclude that this developmentally complex puff site contains six members of the ecdysterone-induced "late"-gene set and one member of the ecdysterone-regulated "intermolt" -gene set. Additional complexity is found at the transcript level: a heterogeneously sized population of RNA molecules arises from each of the seven genes. PMID- 3090271 TI - Crystal structure analysis and refinement at 2.5 A of hexameric C-phycocyanin from the cyanobacterium Agmenellum quadruplicatum. The molecular model and its implications for light-harvesting. AB - The crystal structure of the light-harvesting protein-pigment complex C phycocyanin from the cyanobacterium Agmenellum quadruplicatum has been determined by Patterson search techniques on the basis of the molecular model of C phycocyanin from Mastigocladus laminosus. The crystal unit cell (space group P321) contains three (alpha beta)6 hexamers centred on the crystallographic triads. The hexamer at the origin of the unit cell exhibits crystallographic 32 point symmetry. The other two hexamers (independent of the former) show crystallographic 3-fold and local 2-fold symmetry. The 3-fold redundancy of the asymmetric unit of the crystal cell was used in the refinement process, which proceeded by cyclic averaging, model building and energy-restrained crystallographic refinement. Refinement was terminated with a conventional crystallographic R-value of 0.20 with data to 2.5 A resolution. The two independent hexamers of the unit cell are identical within the limits of error at all levels of aggregation. Two trimers, which closely resemble the M. laminosus C phycocyanin, are aggregated head-to-head to form the hexamer. Both trimers fit complementarily and are held together by polar and ionic interactions. Conservation of the amino acid residues involved in protein-chromophore and intermonomer interactions suggests common structural features for all biliproteins. Most probably, the hexameric aggregation form present in the crystals is closely related to the discs of native phycobilisome rods. All tetrapyrrole chromophores are extended but with different geometries enforced by different protein surroundings. In particular, interactions of the propionic side chains with arginine residues and of the pyrrole nitrogen atoms with aspartate residues define configuration and conformation of the chromophores. Relative chromophore distances and orientations have been determined and a preferential pathway for the energy transfer suggested. Accordingly, within a hexamer the absorbed energy is funneled to chromophore B84 and then transduced via B84 chromophores along the phycobilisome rods. PMID- 3090272 TI - Evaluation of chicken embryo, brine shrimp, and bacterial bioassays for saxitoxin. AB - The chicken embryo, brine shrimp (Artemia salina) and selected bacteria (Staphylococcus epidermidis, Micrococcus flavus, and Bacillus subtilis) were evaluated as alternative test systems for the determination of paralytic shellfish poisoning toxicity (saxitoxin). Dose levels ranging from 0.045 to 0.3 microgram were administered to the developing embryo through the air cell at either 0 or 96 h following incubation. Embryos dosed 96 h after incubation were the most sensitive, with 100% mortality at the 0.11-microgram dose level 24 h following exposure. Embryo mortality was 42% at to 0.3-microgram dose level when the toxin was administered at 0 h. Some embryonic malformations were observed in the 0-h treatment group. Brine-shrimp larvae were sensitive to saxitoxin at a dose level of 5 micrograms. A dose response based on mortality was apparent only 48 h after dosing. Limited growth inhibition was observed with the bacteria tested at concentrations between 0.0035 and 0.35 microgram and 0.35 microgram/well. PMID- 3090273 TI - Diagnosing depression with the DST and TRH in cocaine and opioid abusers. AB - Identifying major depressive disorders in substance abusers is difficult, and the DST and TRH tests have held some promise for making this diagnosis. Studies in alcoholics have been contradictory, but two recent studies using the DST in opiate addicts and the TRH in cocaine abusers may be relevant to clinical practice and future studies. The DST was positive more often in opiate addicts with major depressive disorders than in addicts without this disorder, but the TSH test had many false positives in non-depressed cocaine abusers. Several factors other than depressive disorders may have accounted for these respectively encouraging and discouraging results, and these factors are described in order to design more focused studies. These factors include blinding of clinical raters, using inpatient versus outpatient populations, timing of the testing, and type of opioid used before detoxification and DST testing. PMID- 3090274 TI - Treatment of pain owing to acute ureteral obstruction with prostaglandin synthetase inhibitor: a prospective randomized study. AB - Pain owing to acute ureteral obstruction seems to be related closely to tension in the walls of the renal pelvis. Renal prostaglandins are involved intimately in the events leading to the pain. A prostaglandin-synthetase inhibitor, diclofenac sodium, was used in the treatment of acute ureteral pain, and was compared to the traditional treatment of a combination of spasmolytic and narcotic drugs. Also, the need for overhydration as part of the management was tested. The 91 patients entered into the prospective randomized trial were divided into groups. Diclofenac sodium had a 90 per cent success rate in relieving pain at 30 minutes, and the combination of pethidine and hyoscine butyl bromide had a statistically higher success rate at 97.5 per cent (p equals 0.05). However, the latter therapy had a higher rate of side effects (p equals 0.01). There was no difference in the response between the groups in relation to whether they received intravenous fluids. PMID- 3090275 TI - Intravesical chemotherapy: studies on the relationship between osmolality and cytotoxicity. AB - The effectiveness of intravesical chemotherapy for the treatment of superficial bladder cancer may be influenced by the conditions of administration, such as the osmotic strength of the instillate. Urine from patients with bladder cancer before treatment had osmolalities in the range 187 to 852 mOsm./kg. and these had decreased by an average of 135 mOsm./kg. at the completion of intravesical chemotherapy. Clinical preparations of drugs used for intravesical chemotherapy had osmotic strengths ranging from 65 to 1,038 mOsm./kg. The antitumor activities of the drugs most frequently used intravesically (doxorubicin, epodyl, mitomycin C and thiotepa), and of cisplatin and epirubicin in media of 6 different osmolalities were measured with a human bladder cancer cell line by inhibition of colony-forming ability. Reducing osmotic strength from 590 to 125 mOsm./kg. significantly increased the in vitro cytotoxicities of thiotepa, mitomycin C, cisplatin and epirubicin but not those of doxorubicin and epodyl. We conclude that the use of an instillate at the lowest achievable osmotic strength probably will be optimal for the intravesical administration of chemotherapeutic drugs. PMID- 3090276 TI - Bone marrow suppression after intravesical mitomycin C treatment. AB - Intravesical chemotherapy has been established as a modality for the treatment and prevention of superficial bladder tumors. However, the optimal time for instillation of chemotherapy following transurethral resection is still not clear. We report on a patient with a superficial bladder tumor treated immediately after transurethral resection with relatively high dose mitomycin C. Bone marrow failure developed within 2 weeks. A possible relationship is suggested. PMID- 3090277 TI - Treatment of urothelial carcinoma of the upper urinary tract following prostatocystectomy with mitomycin C instillation in the ileal loop. AB - We report a case of urothelial carcinoma of the upper urinary tract, which developed after prostatocystectomy. The patient was treated with instillations of 40 mg. mitomycin C in 40 ml. saline. No significant systemic side effects owing to perfusion of mitomycin C could be demonstrated. Complete remission of the small urothelial tumors occurred, as well as slight progression of a large pelvic carcinoma of the left kidney. PMID- 3090279 TI - Predictive parameters of successful varicocele repair. AB - A total of 130 men presenting with oligospermia and clinically identifiable scrotal varicoceles was evaluated, treated surgically and followed for 1 year for pregnancy rate. The treatment outcome was compared to an age-matched cohort of 83 oligospermic men who had received empirical medical therapy with clomiphene citrate (25 mg. per day) for the same 1-year interval. This study was done to contrast treatment modalities in infertility and not as a strict control. Only eugonadotropic patients in both groups were used for comparison. In the varicocele group the over-all pregnancy rate was 38.5 per cent. Four variables (a lack of testicular atrophy, sperm density greater than 50 million per ejaculate, sperm motility 60 per cent or more and serum follicle-stimulating hormone values less than 300 ng. per ml.) proved to be accurate preoperative predictors of postoperative pregnancy success. Four other variables (varicocele size and laterality, sperm forward progression greater than 2 and normal sperm morphology 60 per cent or more) did not yield statistically significant rates of improvement in pregnancy postoperatively. The pregnancy rate of the eugonadotropic patients undergoing varicocele repair was 45.8 per cent. Despite statistical similarity in patient age, sperm density and mean gonadotropin levels the medically treated patients had a pregnancy rate of only 25.5 per cent, significantly lower than the surgically treated patients. In summary, patients with an identifiable varicocele had a greater chance of achieving a pregnancy following surgical correction than did those treated with empirical drug therapy. In addition, certain preoperative variables in the physical and laboratory analyses appeared to portend a greater surgical response. PMID- 3090278 TI - Evaluation of misoprostol cytoprotection of the bladder with cyclophosphamide (Cytoxan) therapy. AB - Cyclophosphamide is a well established cytotoxic drug used in the treatment of lymphoproliferative disorders, certain solid tumors, and nonneoplastic disorders such as nephrotic syndrome, systemic lupus erythematosus and rheumatoid arthritis. Hemorrhagic cystitis can be a complication of this drug varying between two and 40 per cent. Misoprostol, which is a synthetic prostaglandin E1 analog, was found to significantly decrease the histological damage to the bladder from cyclophosphamide. Male rats receiving misoprostol in conjunction with cyclophosphamide were found to have a reduction in ulceration, inflammation and edema of the bladder walls as compared to those treated with cyclophosphamide alone. PMID- 3090280 TI - Caliceal diverticula developing into simple renal cyst. AB - Although common in adults simple cortical renal cysts are rare in children. Caliceal diverticula are rare in adults and children. A case of a caliceal diverticulum apparently sealing off and becoming an isolated simple cyst in the renal parenchyma has been reported as an unusual complication of caliceal diverticula. There have been 2 other cases of caliceal diverticula becoming sealed off reported in the literature, although neither progressed to frank cysts. We report 2 cases of definite caliceal diverticula progressing to simple renal cortical cysts. PMID- 3090281 TI - Antitumor activity of Lactobacillus casei (LC 9018) against experimental mouse bladder tumor (MBT-2). AB - The purpose of this paper is to investigate the inhibitory effect of Lactobacillus casei (LC 9018) on the growth of transplantable murine bladder tumor. Lactobacillus casei, viable and/or heat-killed bacteria, either in oral or intravenous administration, produced a significant inhibitory effect on the tumor growth and much less pulmonary metastasis. PMID- 3090283 TI - Sparganosis in a saddle-back tamarin: another case of viral-induced proliferation? PMID- 3090282 TI - Effects of continuous intravenous infusions of nitroglycerin on canine systemic and hind limb microcirculatory hemodynamics. AB - Systemic and hind limb hemodynamics were assessed in anesthetized dogs during continuous 30-minute intravenous infusions of nitroglycerin at 1, 5, 10, and 25 micrograms/kg/min. Nitroglycerin at 1 microgram/kg/min redistributed hind limb blood flow; hind limb arteriovenous shunting increased from 5.6% +/- 4.0% to 17.8% +/- 7.4% after 30 minutes (p less than 0.01); absolute hind limb shunt flow increased from 12 +/- 10 ml/min to 31 +/- 26 ml/min at 10 minutes (p less than 0.01); whereas hind limb nutrient blood flow decreased from 184 +/- 81 ml/min to 150 +/- 55 ml/min and 132 +/- 32 ml/min, respectively, at 10 and 30 minutes (p less than 0.05). Such hind limb blood flow redistribution was absent during infusion of all other nitroglycerin dosages. Total catecholamines increased at 30 minutes during both 1 and 10 micrograms/kg/min nitroglycerin infusions (p less than 0.05) with perhaps a slightly greater catecholamine response to 10 micrograms/kg/min after 30 minutes (0.05 less than p less than 0.10). The renin angiotensin response at 3 minutes differed between nitroglycerin infusions of 1 and 10 micrograms/kg/min with an initial significant reduction from baseline in plasma renin activity at the lower dose compared with a significant increase from baseline in plasma activity at the higher dose. Nitroglycerin did not increase femoral artery flow or cardiac output and did not lower total peripheral vascular resistance at any dose studied. Despite this, arterial pressure and cardiac work were reduced at all nitroglycerin doses tested. Massive volume loading prevented the anticipated blood pressure reduction and blunted the expected cardiac work reduction during nitroglycerin infusions of 10 micrograms/kg/min. This study demonstrates that nitroglycerin is not a potent peripheral arteriolar vasodilator, 1 microgram/kg/min nitroglycerin infusions increase hind limb arteriovenous shunting and decrease hind limb nutrient blood flow, and myocardial work and arterial pressure reductions during nitroglycerin infusions appear to be caused by mechanisms other than generalized peripheral arterial dilation. PMID- 3090284 TI - Mass mortality of bats due to probable blue-green algal toxicity. PMID- 3090285 TI - Low-frequency positive-pressure ventilation with extracorporeal CO2 removal in severe acute respiratory failure. AB - Forty-three patients were entered in an uncontrolled study designed to evaluate extracorporeal membrane lung support in severe acute respiratory failure of parenchymal origin. Most of the metabolic carbon dioxide production was cleared through a low-flow venovenous bypass. To avoid lung injury from conventional mechanical ventilation, the lungs were kept "at rest" (three to five breaths per minute) at a low peak airway pressure of 35 to 45 cm H2O (3.4 to 4.4 kPa). The entry criteria were based on gas exchange under standard ventilatory conditions (expected mortality rate, greater than 90%). Lung function improved in thirty-one patients (72.8%), and 21 patients (48.8%) eventually survived. The mean time on bypass for the survivors was 5.4 +/- 3.5 days. Improvement in lung function, when present, always occurred within 48 hours. Blood loss averaged 1800 +/- 850 mL/d. No major technical accidents occurred in more than 8000 hours of perfusion. Extracorporeal carbon dioxide removal with low-frequency ventilation proved a safe technique, and we suggest it as a valuable tool and an alternative to treating severe acute respiratory failure by conventional means. PMID- 3090286 TI - Studies of breast-feeding and infections. How good is the evidence? AB - We assessed the extent to which studies of the association between breast-feeding and infection met four important methodological standards that relate to both the scientific validity and the generalizability of the studies. Of the 20 studies (14 cohort, six case-control), only six met three or four of the methodological standards. Four of these six studies found that breast-feeding was not protective against infections and two found that breast-feeding was protective against infections. In the three studies in which statistical adjustments were made for three additional potentially important confounding variables--size of the family, smoking of cigarettes by the mother, and the mother's level of education-the apparent protective effect of breast-feeding against respiratory tract infections disappeared after the adjustments were made. We found that most of the studies have major methodological flaws that may have compromised their conclusions. The studies that met important methodological standards and controlled for confounding variables suggest that breast-feeding has at most a minimal protective effect in industrialized countries. PMID- 3090287 TI - Diagnosis of hypothyroidism. PMID- 3090288 TI - Thyroid hormones and TSH in normal subjects. PMID- 3090289 TI - The negative nitrogen balance in post-operative paediatric patients. PMID- 3090290 TI - Effects of nutrition on the management of cirrhosis. PMID- 3090291 TI - Duration of lactation, lactational amenorrhoea and incidence of pregnancy in Pakistani women. PMID- 3090292 TI - Radionuclide evaluation of the superior vena cava and upper thoracic veins in mediastinal syndrome. PMID- 3090293 TI - Carcinoma of the middle ear. A case report. PMID- 3090294 TI - Carcinoma of the oesophagus. PMID- 3090295 TI - Microflora in pregnancy. PMID- 3090297 TI - Studies on the physical and bacterial quality of Dahi with special reference to public health. PMID- 3090296 TI - Diarrhoea in children due to enterotoxigenic Escherichia coli. PMID- 3090298 TI - Quantitative and qualitative microbial load determination from meat samples effected by time and temperature. PMID- 3090299 TI - [The suppressive effect of pyrrole-2-carboxylic acid on platelet aggregation]. AB - In the course of a search for novel antibiotics, an antiplatelet substance was isolated from the fermentation broth of Streptomyces sp. No. 82-85. Thereafter, the active substance was identified as pyrrole-2-carboxylic acid (P2C) by structural studies. The effects of P2C on adenosine diphosphate (ADP)-, arachidonic acid-, collagen- or tumor cell-induced platelet aggregation were examined in vitro and ex vivo. In in vitro studies, P2C (25-100 micrograms/ml) suppressed the aggregation of platelets of normal Wistar rats. The intraperitoneal administration of P2C (200 mg/kg) to rats and rabbits suppressed platelet aggregation induced by ADP, arachidonic acid and collagen when examined for 0.5-3 hours after administration. The agent also suppressed platelet aggregation induced by both mouse syngenic tumors, Meth-A fibrosarcoma and IMC carcinoma in vitro. PMID- 3090300 TI - [Plasmid replication and partition in E coli and sex pheromones and plasmid transfer in Streptococcus faecalis]. PMID- 3090301 TI - [Clinical study of THP-adriamycin in patients with advanced gastric cancer]. AB - To evaluate the therapeutic effects of THP-adriamycin (THP), single agent chemotherapy and combination chemotherapy with THP were undertaken in 16 patients with advanced gastric cancer. In the eight patients in the THP single agent group. Only three minor responses (MRs) were obtained. However, three partial remissions (PRs) and one MR were observed in the eight patients in the THP combination group. In which 5-FU was two patient FT-207 in another two and CDDP in one. No severe side effects were observed with the THP chemotherapy, while leukopenia of less than 3,000/mm was commonly seen (69%). Only three patients showed alopecia. Thrombocytopenia of less than 30,000/mm3 and transient arrhythmia were observed in one patient each. These side effects were apparently milder than those with adriamycin. From a pharmacokinetic study of THP and adriamycin. It was found that THP was superior to adriamycin in its transferability from the blood to cancer tissue. In conclusion, it is suggested that combination chemotherapy with THP is useful for advanced gastric cancer. PMID- 3090302 TI - [A case of colon cancer associated with schistosomiasis japonica]. AB - A case of colon cancer associated with schistosomiasis japonica is reported. A 60 year-old man was admitted with the complaint of melena. Barium enema study revealed a colon tumor (type 1') 11 cm from the anal ring. Sigmoidectomy was performed, and no lymph node metastasis was observed. Histologically, the tumor was diagnosed as well-differentiated adenocarcinoma, and also many schistosoma ova were found not only in the lesion of the carcinoma, but also in the tissue surrounding the carcinoma. In the latter lesion, ova were observed beneath muscularis mucosae. The distributions of the ova in the anal side of the tumor were more dominant than those in oral side. We review the direct correlation between gastrointestinal tract cancer and the schistosomiasis japonica in other reports. PMID- 3090303 TI - [A case of Waldenstrom's macroglobulinemia with cold agglutinin disease]. PMID- 3090304 TI - [Acquired pure red cell aplasia associated with malignant B cell lymphoma]. PMID- 3090305 TI - [A case of post-hepatitis aplastic anemia showing serum inhibitory activity against hematopoietic progenitor cells]. PMID- 3090306 TI - [Growth hormone releasing factor--the chemical structure, biosynthesis and body distribution]. PMID- 3090307 TI - [Growth hormone releasing factor tolerance test]. PMID- 3090308 TI - [Methods of analysis of growth hormone releasing factor]. PMID- 3090309 TI - [Biosynthesis of pituitary hormones--gene organization and processing--thyroid stimulating hormone]. PMID- 3090310 TI - [Secretory control of pituitary hormones--mechanism of TSH secretory control]. PMID- 3090311 TI - [Secretory regulation of pituitary hormones--ADH]. PMID- 3090312 TI - [Pituitary dwarfism--progress of therapy]. PMID- 3090313 TI - Phase II study of UFT in patients with advanced non-small cell lung cancer. AB - A phase II study of UFT (a mixture of uracil and tegafur; molar ratio of uracil to tegafur = 4) was undertaken in 21 patients with advanced non-small cell lung cancer (NSCLC). UFT was administered orally at a dose of 400 mg/m2 every day, for more than four weeks. Of 16 adequately treated patients, one (6.3%) showed a partial response. Toxic effects included minimal myelosuppression, anorexia, nausea, vomiting and epigastralgia. Gastrointestinal toxicity was well tolerated. Considering the poor response and mild toxicity, a further phase II study of higher-dose UFT is necessary for patients without prior therapy. PMID- 3090314 TI - The protective effect of 2-mercapto-ethane sulfonate (MESNA) on hemorrhagic cystitis induced by high-dose ifosfamide treatment tested by a randomized crossover trial. AB - High-dose ifosfamide (one or two courses of 6 g/m2) with or without mesna was administered to 13 patients with advanced non-small cell lung cancer. The protective effect of 2-mercapto-ethane sulfonate (mesna) against the urotoxic side effects induced by ifosfamide was examined by a randomized crossover trial. A significant reduction in the incidence of hematuria was observed in the patients receiving mesna. Macroscopic hematuria was observed in only one patient who received treatment with mesna versus seven patients treated with ifosfamide alone. Other symptoms, such as frequency and dysuria, tended to be diminished in the patients receiving mesna, although the difference was not statistically significant. Our results suggest that mesna is effective in preventing or diminishing ifosfamide-induced hemorrhagic cystitis. Concomitant use of mesna should allow the administration of a high dose of ifosfamide although more extensive studies are needed to define the optimal dose and schedule of administration of mesna to prevent or attenuate the hemorrhagic cystitis. PMID- 3090316 TI - [Intra-oral electron therapy of carcinoma of the oral cavity using transparent acrylic tubes]. PMID- 3090315 TI - A case of advanced gastric cancer with long-term survival as the results of combined radiation therapy and chemotherapy. AB - A case report on a long-term surviving patient with advanced gastric cancer with supraclavicular lymph node metastasis treated by radiation and chemotherapy is presented. The Borrman type 2 of advanced gastric cancer was found on the greater curvature of the antrum at the first radiological examination. Radiation was administered to the supraclavicular lymph node at 60 Gy and to the stomach at 64 Gy. The patient received mitomycin C (24 mg) and Tegafur (230 g). After completion of the combined therapy the endoscopy revealed an irregular mucosal change with erosion and hemorrhage. Radiological examination revealed atrophic and hyperplastic areas throughout the stomach. These findings lasted more than six years. The patient died of unknown cause in February 1983. She had survived nine years and seven months after her initial diagnosis. Radiotherapy may play a role as a means of radical treatment in certain cases of advanced gastric cancer. PMID- 3090317 TI - Population studies on Oncomelania quadrasi, the snail intermediate host of Schistosoma japonicum, in the Philippines. 5. Quantitative analysis on successful snail control by land reclamation. AB - For the control of Oncomelania quadrasi, environmental modifications, i.e., clearing of vegetation, leveling of swampy depression and draining of stagnant water by channeling and excavation were carried out at 3 areas in Leyte, Philippines from 1974 to 1977. The change of snail population resulted in the land reclamation was evaluated by the methods previously developed by the population studies on this snail. As a result of statistical analysis based on y = log(x + 0.01) transformation and the antilogarithmic mean density A-y = (antilog -y) -0.01, the reduction of snail population was observed at 13 out of 18 sites studied at 3 project areas and the significant reduction was statistically confirmed at 9 sites of them. Particularly at Dagami area, which was a wide and heavily snail-infested land adjacent to Dagami Poblacion, the reduction rate of snail density reached 87.7% to 99.2% and some wet depressions have been converted into good rice fields with little snail infestation at the last survey. PMID- 3090319 TI - [Immunohistochemical study on interleukin-2 receptor positive cells in regional lymph nodes in gastric cancer]. PMID- 3090318 TI - [Clinical significance of chronic schistosomiasis japonica--histological detection of ova of Schistosoma japonicum]. PMID- 3090320 TI - A complex mosaic with tdic(13;18) (p11;p11), +13p-, +18p-, r(13) etc. in a male infant. II. Increased dissociation of dicentric chromosome by mitomycin C. PMID- 3090321 TI - Melittin-stimulated antimycobacterial activity of the membrane fraction isolated from phagocytes of guinea pigs. AB - Virulent tubercle bacilli were incubated in Kirchner semi-solid agar medium with the membrane fraction prepared from guinea-pig peritoneal exudate cells. A marked inhibition of mycobacterial growth was observed in the presence of added melittin which is known as an activator of membrane phospholipase A. The bactericidal activity in a buffer environment was also demonstrated by the fraction alone and that stimulated by melittin. PMID- 3090322 TI - Bactericidal activity of the membrane fraction isolated from phagocytes of mice and its stimulation by melittin. AB - The membrane fraction prepared from mouse peritoneal exudate cells was incubated with mycobacteria, staphylococci, or E. coli in acetate buffer of pH 5.6 to follow the fate of viable bacilli. The membrane fraction exhibited bactericidal effect on mycobacteria and staphylococci, but not on E. coli. The activity to kill mycobacteria, as well as the endogenous phospholipase A2 activity, of the membrane fraction was markedly enhanced by melittin, a basic peptide from bee venom, and inhibited by indomethacin and EDTA. The role of the enzyme activity in the bactericidal activity was discussed. PMID- 3090323 TI - [Experimental glomerulopathy induced by monocrotaline in rats]. PMID- 3090324 TI - [HPN (home parenteral nutrition). An interview with Dr. Yoshiya Majima, the First Department of Surgery, Chiba University School of Medicine]. PMID- 3090325 TI - [Actions to restore the deglutition function of a patient after prolonged tube feeding: oral feeding of a patient with cerebral infarction]. PMID- 3090326 TI - [Nutritional care of patients undergoing esophagectomy]. PMID- 3090327 TI - [Nursing of an aged patient with esophageal cancer who lacked a desire for recovery]. PMID- 3090328 TI - Evaluation of uneven distribution of VA/Q ratio from data on exchange of respiratory gases. AB - A new approach has been developed for evaluating uneven distribution of ventilation/perfusion ratio, VA/Q, based on a two-compartment model with a reciprocal VA/Q relation. The VA/Q ratios were expressed by mu . (1-rho)/rho and mu . rho/(1-rho), where mu and rho were referred to as the "ideal" VA/Q ratio and unevenness factor, respectively. During steady state breathing, arterial blood was analyzed for PO2 and PCO2, and end-tidal PCO2 as well as the gas exchange ratio, R, was measured. After steady state breathing a rebreathing experiment was performed, and the arterial-venous O2 content difference, (a-v)CO2, was measured, and then, multiplying it by R, the venous-arterial CO2 content difference, (v a)CCO2, was obtained. Referring to these values the mixed venous PO2 and PCO2 were estimated from arterial PO2 and PCO2, using the O2 and CO2 dissociation curves. The VA/Q line and iso-R line were drawn to find mu, and further, total arterial, and alveolar PO2 and PCO2 of the two-compartment model were computed by changing both rho and the mixing weight factor, phi. The phi value was determined so as to make the above PO2-PCO2-locus pass through the measured arterial PO2 and PCO2. The rho value was selected so that the computed alveolar PCO2 fitted to the end-tidal one. The experiments were performed on 8 normal subjects in normoxia and hyperoxia with PIO2 245 Torr. The mean phi values in normoxia and hyperoxia were 0.50 and 0.56, respectively. The mean rho values in normoxia and hyperoxia were 0.438 and 0.428, respectively. The VA/Q ratio was decreased in hyperoxia because of a decrease in VA value. PMID- 3090329 TI - The effects of extracellular calcium removal on sino-atrial node cells treated with potassium-depleted solutions. AB - The effect of extreme calcium reduction was studied in rabbit sino-atrial node cells treated with K-free media. Ca removal (Ca = 0, EGTA = 6 mM) suppressed spontaneous miniature fluctuations elicited by exposure to the K-free media. Further, successive exposure to the Ca-free, EGTA solutions produced a propagated action potential and suppressed a contracture. The action potential was not noticeably altered by tetrodotoxin (TTX). In the presence of normal Ko, reducing the bathing calcium concentration with EGTA prolonged the duration of the action potential. The potential induced by Ca removal was similar to that observed in the K-free media. From these results, we have concluded that a drastic reduction in the extracellular Ca concentration produces a decrease in the overloaded Ca in the cell exposed to the K-free media, resulting in an increase in the amplitude of action potentials. PMID- 3090330 TI - Functional compensation by transplantation of cell suspensions of embryonic mesencephalon into the striatum of rats with 6-hydroxydopamine lesions. AB - Neuronal cell suspensions were implanted into the striatum of female rats that showed apomorphine-induced rotation and a reduction in striatal dopamine after intranigral treatment with 6-hydroxydopamine. The apomorphine-induced rotation was significantly suppressed by the transplantation in 12 out of 64 rats. DOPA accumulation and dopamine level (6.3 and 3.4%, respectively, compared with those of uncompensated rats) in the striatum following treatment with an amino acid decarboxylase inhibitor were slightly restored in compensated rats. PMID- 3090331 TI - Changes of tissue blood flow in mice loaded with SART (repeated cold) stress or restraint and water immersion stress and the effect of administered neurotropin. AB - In order to explore the peripheral microcirculation and to obtain an outline of autonomic innervation in SART (specific alternation of rhythm in temperature) stressed (repeated cold-stressed) animals, which are regarded as model animals for clinical vagotonic-type dysautonomia, peripheral tissue blood flow was determined in mice, using the hydrogen clearance method. SART-stressed mice showed a decrease in gastric blood flow, no change in hepatic blood flow and an increase in dermal blood flow. In the mice exposed to the restraint and water immersion stress (RWIS), a type of acute stress, in contrast with SART stress which is a subacute type, remarkable decreases were observed in gastric, hepatic and dermal blood flows. Changes of both gastric and dermal blood flow in SART stressed mice were dose-dependently prevented and maintained within normal limits by the treatment with Neurotropin, a sedative analgesic which is an extract isolated from vaccinia virus-inoculated and inflamed skin of rabbits. In RWIS loaded mice, Neurotropin exhibited a great preventive effect on changes of blood flow in the stomach, a slight effect in the liver, and no effect in the cutis. When mice were loaded with SART stress after left-cervical vagotomy, SART stress failed to elicit any decrease in gastric blood flow. In SART-stressed mice treated with 6-hydroxydopamine, gastric and dermal blood flows tended to show a further decrease and increase, respectively, over and above the changes caused by SART stress. From these results, it is suggested that SART-stressed mice may have decreased gastric parasympathetic tone, a decrease in sympathetic tone and also other anomalies such as increased tension of the sympathetic cholinergic vasodilator nerves in the cutis. PMID- 3090332 TI - Postoperative adjuvant chemotherapy for gastric cancer, the second report. Analysis of data on 2873 patients followed for five years. AB - The effectiveness of combination chemotherapy with mitomycin-C (MMC) plus futraful (N1-(2'-tetrahydrofuryl)-5-fluorouracil), as an adjunct to surgery for gastric cancer was investigated in a prospective randomized controlled study. Three thousand and thirty-three Japanese patients in 344 hospitals were entered and 2873 could be followed for 5 years. All patients had undergone gastrectomy from April 1977 to May 1979 and were assigned, at random, to either Groups A, B or C. In Group A, bolus MMC was administered with no further treatment. In Group C, oral futraful was given for one year, without MMC induction. In Group B, both a bolus MMC injection and oral futraful were prescribed. This randomized study showed no statistical difference in the 5 year survival rate among the three groups. However, in patients given MMC and put on oral futraful for one year, the 5 year survival rate for those with stage III gastric cancer or for those with positive lymphnode metastasis plus obvious serosal invasion seemed to be improved. PMID- 3090334 TI - [Effect of inspiratory resistive loading on the relationship between occlusion pressure and diaphragmatic EMG during CO2 inhalation in patients with chronic obstructive pulmonary disease]. PMID- 3090333 TI - Correlation of an in vitro chemosensitivity test using [3H] incorporation with the response in case of human tumor chemotherapy. AB - We developed a method for performing in vitro drug testing using [3H] incorporation into a primary human tumor. The test was applied to specimens from 60 patients with advanced malignancies, mainly gastrointestinal cancers. Forty six specimens had sufficient growth for the drug testing. Forty-seven per cent of the gastric cancer specimens and 67 per cent of those from patients with colorectal cancer demonstrated an in vitro chemosensitivity. Among 9 chemotherapeutic drugs tested, ara-C, 5-fluorouracil, and mitomycin C showed the high percentages of positive sensitivity for gastric cancer, whereas actinomycin D, carboquone, and nimustine hydrochloride were sensitive in case of colorectal cancer. Clinical responses were compared with the results of the test. In 46 drug assays, in vitro/in vivo drug responses correlated in 78 per cent, with a true positive rate of 47 per cent and a true-negative rate of 94 per cent. This test appears to be a reliable indicator for the clinical response to the same chemotherapeutic drugs in cases of the malignant diseases seen clinically. PMID- 3090336 TI - Enhancement of antibody production against sheep erythrocytes using Theileria sergenti lysate antigen in different strains of inbred mice. PMID- 3090335 TI - Factors affecting superovulation response in cattle. PMID- 3090337 TI - A rise and fall of humoral antibody in calves experimentally infected with Babesia ovata or Theileria sergenti. PMID- 3090338 TI - Biochemical and ultrastructural study of Leu M1 antigen in Reed-Sternberg cells: comparison with granulocytes and interdigitating reticulum cells. AB - A group of monoclonal antibodies was shown to react with glycoconjugates containing a sugar sequence--lacto-N-fucopentaose III (LNF-III)--in granulocytes and in some normal nonlymphoid cells. The antibodies including anti-Leu M1, anti My-1, WGHS 29-1, 534F-8, and 538F-12 of the immunoglobulin M-type were used to study the biochemical properties of LNF-III antigens in granulocytes, interdigitating reticulum cells, and neoplastic cells of Hodgkin's disease. In contrast to the presence of an abundant LNF-III glycolipid in granulocytes, the Hodgkin's neoplastic cells had no LNF-III glycolipid or contained only minimal amounts; however, both LNF-III glycoconjugates isolated from Hodgkin's neoplastic cells and interdigitating reticulum cells appeared to be a similar, if not an identical, 150,000-molecular-weight glycoprotein. The neoplastic cells in Hodgkin's disease appeared to show a biochemical property more closely related to interdigitating reticulum cells than any other cells in the monocyte-granulocyte histiocyte system. PMID- 3090339 TI - Importance of Lyt 1+ T-cells in the antitumor activity of an immunomodulator, SSM, extracted from human-type Tubercle bacilli. AB - An arabinomannan lipid extracted from Mycobacterium tuberculosis strain Aoyama B (SSM) is an immunopotentiating agent with interferon-inducing and antitumor activities. In the present study, the possible role(s) of various immunocompetent cells on the antitumor effect of SSM was investigated in mice bearing syngeneic (RL male 1 leukemia) and allogeneic (Ehrlich carcinoma) ascites tumors. When Thy 1+ T-cells were depleted from tumor-bearing mice by the administration of monoclonal anti-Thy 1.2 antibody, the protective effect of SSM was eliminated. However, when macrophage (M phi) and natural killer (NK) cell activities were depleted by treatment with M phi blockers (trypan blue and carrageenan) or a blocker for NK cells (anti-asialo GM1 antiserum), no alteration of the antitumor activity of SSM was observed. Therefore, T-lymphocytes, but not M phi or NK cells, were required for the expression of the antitumor efficacy of SSM. The antitumor activity of SSM was also abrogated by Lyt 1+ T-cells being depleted by treatment with monoclonal anti-Lyt 1.2 antibody, whereas the administration of monoclonal anti-Lyt 2.2 antibody had no effect on the antitumor activity. Independent of M phi, NK cells, or Lyt 2+ T-cells, Lyt 1+ T-lymphocytes appear to play an important role in the expression of the antitumor effects of SSM. PMID- 3090340 TI - Spontaneous neurinoma in an African lungfish, Protopterus annectens, and DNA repair studies on normal and neoplastic tissues. AB - Neurinomas developed in an African lungfish (Protopterus annectens), living in an aquarium in Western Japan. The 2 tumors, measuring 7.5 X 9.0 X 6.5 and 13 X 4 X 6 cm, were located on the skin. As shown by light microscopy, tumor cells were composed of spindle-shaped cells with huge pleomorphic nuclei, which were arranged in parallel rows or whorls in interlacing connective tissue. Long-term culture of these tumor cells was achieved in vitro at 25 degrees C with use of conditioned medium over a period of more than 4 months. The nuclear DNA contents of erythrocytes (normal diploids, 2C) and tumor cells dispersed from the fixed tumor tissues were measured by 4',6-diamidino-2-phenylindole hydrochloride-DNA microfluorometry by using mouse cerebellar small granule cells (normal diploids, 2C) as a reference. The 2C value of the lungfish was approximately 28-fold greater than that of the mouse. Furthermore, consistent with the nuclear pleomorphism observed by light microscopy, the nuclear DNA contents of tumor cells showed a wide distribution from hypo-2C to hyper-4C. DNA repair synthesis was measured autoradiographically in organ cultures of the tumor, lung, and skin, exposed to chemical carcinogens or UV radiation. Considerable repair was observed in the tumor and skin cells exposed to 1-methyl-1-nitrosourea (CAS: 684-93-5), N methyl-N'-nitro-N-nitrosoguanidine (CAS: 70-25-7), or 254-nm or sunlamp UV light. Only traces of repair synthesis were detected in lung exposed to 1-methyl-1 nitrosourea or N-methyl-N'-nitro-N-nitrosoguanidine. 4-Hydroxyaminoquinoline 1 oxide (CAS: 4637-56-3) did not induce repair in any of the three tissues. The observed values for repair, relative to the amount of DNA, were similar to those in other fishes. PMID- 3090341 TI - Thyroid hormones and experimental cancer cachexia. AB - The relationship between circulating thyroid hormones and nutritional status was studied in sarcoma-bearing inbred C57BL/6J mice and control mice. Supplementation with exogenous thyroxine (T4) was also evaluated. Tumor-bearing animals had depressed levels of circulating thyroid hormones. This was also found in food restricted (pair-fed and pair-weighed) controls. Plasma levels of thyroid hormones decreased with increased tumor burden. Thyrotropin-releasing hormone caused an increased response of thyroid-stimulating hormone in tumor-bearing animals. Low levels of thyroid hormones in sarcoma-bearing mice were due to depressed hormone production by the thyroid gland rather than to increased clearance rate of hormones. Plasma levels of triiodothyronine (T3) correlated to the amount of whole-body nitrogen among sarcoma-bearing mice and food-restricted controls. Exogenous T4 increased food intake by 20% in sarcoma-bearing mice. The benefit of this was probably counteracted by an increased metabolic rate, since reversal of plasma levels of T3 and free T4 had no net effect on body composition of freely eating sarcoma-bearing mice, although it had a negative effect on body and muscle composition in food-restricted controls. Exogenous T4 did not stimulate tumor growth. The results indicate that low circulating levels of thyroid hormones in experimental cancer cachexia are probably caused by the reduced food intake (anorexia), which is in agreement with findings in clinical cancer. Depression of thyroid hormones is probably a physiological means to reduce energy expenditure and to preserve substrates in progressive cancer disease. PMID- 3090342 TI - [Comparative studies on in vitro activities of important antituberculous drugs]. PMID- 3090343 TI - [Compensatory factors in acute failure of the isolated heart]. AB - The cardiac output of isolated guinea-pig hearts fell during progressive infusion of Ca2+-complexon, EGTA, or oxidative phosphorylation inhibitor dinitrophenol. Moderate doses of EGTA (0.3-0.6 mM) caused an apparent diminution of the left ventricular +dP/dt and aortic pressure amplitude but did not influence cardiac output, which was maintained due to a prolongation of the contraction time. When the left-atrial cavity was greatly reduced by ligation, cardiac output fell by 40 per cent while left-ventricular systolic pressure and +dP/dt remained unchanged. In these conditions, EGTA in the same concentration reduced cardiac output by 30 per cent thus proving the important role of the left atrium in the compensation of hypocalcemic heart failure. On the contrary, the infusion of dinitrophenol shortened contraction time and increased myocardial rigidity. The latter change facilitated force development thus contributing to a lesser fall of +dP/dt and aortic pressure amplitude at equal diminution of cardiac output as compared to EGTA action. However, this compensation required a higher elevation of the filling pressure for inflow maintenance. PMID- 3090344 TI - [Role of carbon dioxide in the maintenance of positive changes in myocardial metabolism and the mechanisms of cardiac regulation after physical exercise training]. AB - Four-percent carbon dioxide added to the gaseous medium during swimming exercise under normoxia increased animals' working capacity, myocardial contractility, the stability of myocardial acetylcholine store and cardiac choline reactivity, and contributed to post-exercise retention of those changes. Three months' training under the same conditions caused no further increment in adaptation parameters, while potentialities of the parasympathetic regulation mechanism even declined, and the acquired changes were promptly lost upon discontinuation of exercise. Mechanisms of action and significance of carbon dioxide in the formation of adaptation and after-effect circulatory stability are discussed. PMID- 3090345 TI - [Vertical transmission of non-A, non-B hepatitis virus. Findings in children of mothers with chronic non-A, non-B hepatitis]. PMID- 3090346 TI - [Diphosphonate for the prevention of an increased ossification process]. PMID- 3090347 TI - [DRGs; its entity and effect on nursing]. PMID- 3090348 TI - [Can basic numbers be solved by new calculation methods? Use of basic numbers in the calculation of personnel needs oriented to care categories]. PMID- 3090349 TI - [Variable annual target work time in the care and function field as a basis for personnel need determination? Seasonal personnel need determination in the hospital. Possibilities in the determination of basic numbers and in the influencing of personnel staffing in the hospital by nursing administration]. PMID- 3090350 TI - [Starting point of a formula for personnel need calculations]. PMID- 3090351 TI - [The status of psychiatric patients]. PMID- 3090352 TI - [Psychiatry in the general hospital]. PMID- 3090353 TI - [Concepts on service administration on the basis of the professional nursing image of the German Nurses' Association]. PMID- 3090354 TI - [The Agnes-Karll Archives in Kaiserswerth]. PMID- 3090355 TI - [Analysis of the status of hospitalized patients. Comparative study between a German and a Tanzanian hospital]. PMID- 3090356 TI - [Current legal questions. Refusal to work by a nurse based on a matter of conscience]. PMID- 3090357 TI - [Health as a pre-condition of patient-oriented nursing]. PMID- 3090358 TI - [Health and quality of life--a concern in nursing for the future]. PMID- 3090359 TI - [Florence Nightingale--a remarkable woman followed her calling]. PMID- 3090360 TI - [Self realization of a nursing student. A letter, written 80 years ago, gives insights into the 14-hour working day]. PMID- 3090361 TI - [How the journal Krankenpflege is produced]. PMID- 3090362 TI - [Are reference numbers replaced by new calculation methods? Instead of reference numbers: calculation of personal requirements informed by nursing categories (part III and temporarily last number)]. PMID- 3090363 TI - [Health education in nursing education]. PMID- 3090365 TI - [Taking time for each other--to whom is what how important?]. PMID- 3090364 TI - [Better integration of the student into the activities of the ward. Goal-oriented integration during the first week is of decisive importance]. PMID- 3090366 TI - Comment on the finding of Ia expression in nonlymphoid cells. PMID- 3090367 TI - Induction of MHC-determined antigens in the lung by interferon-gamma. AB - Recombinant murine interferon-gamma (IFN-gamma) was administered in 6 to 9 daily intraperitoneal injections to B10.BR (H-2k) mice. The distribution of some selected class I and II major histocompatibility complex-determined antigens was localized by immunocytochemistry with the use of anti-H-2Kk and anti-IAk monoclonal antibodies and avidin-biotin-peroxidase in unfixed, frozen lungs for light microscopy and in fixed lungs for electron microscopy. In normal control mice no class I antigens were detected in the lung either by light microscopy or by ultrastructural immunocytochemistry. After 6 to 9 days of IFN-gamma administration, class I antigens were detectable on the endothelium of major vessels and diffusely throughout the alveolar region, presumably on alveolar capillary endothelium. Class I antigens did not withstand chemical fixation, therefore, could not be localized at the ultrastructural level. In normal, control mice class II antigens were detectable on a few interstitial macrophages, on some circulating monocytes, and on elongated cells adjacent to airways and major vessels. After 6 to 9 daily injections of IFN-gamma, larger numbers of macrophages and elongated cells, believed to be dendritic cells, were present around major airways and vessels. In addition, numerous round cells stained throughout the alveolar region. By electron microscopy these round cells included intraalveolar macrophages, although not all alveolar macrophages expressed IAk, circulating monocytes in capillary lumens, and type II pneumocytes. Type I pneumocytes had no detectable IAk. Reaction product in type II cells was limited to the basolateral membranes. Airway epithelium and endothelium remained unstained. These observations indicate that in addition to monocytes/macrophages IFN-gamma induces the expression of class II antigens on type II pneumocytes. PMID- 3090368 TI - Stimulation of the scavenger receptor on monocytes-macrophages evokes release of arachidonic acid metabolites and reduced oxygen species. AB - Mouse peritoneal macrophages are endowed with a scavenger receptor recognizing modified low density lipoproteins (LDL). Metabolic sequelae of receptor occupancy distinct from lipoprotein processing were examined. Adherent peritoneal macrophages were kept in short term culture. Release into culture supernatants of the arachidonic acid derived eicosanoids prostaglandin E, 6-keto-prostaglandin F1a, thromboxane B2, and leukotriene C4 was assessed, and production of reduced oxygen species superoxide anion and hydrogen peroxide, generated in the oxidative burst, was monitored after challenge of macrophages with acetylated or malondialdehyde modified LDL. Modified LDL at concentrations ranging from 50 to 250 micrograms of protein/ml was noted to augment macrophage arachidonic acid metabolism within 6 hours of addition. Cyclo-oxygenase derivatives were synthesized predominantly, but leukotriene C4 generation was also observed. Further, scavenger receptor occupation triggered the release of superoxide anion and hydrogen peroxide which was more rapid in onset and plateaued after 60 minutes of incubation. Human monocyte-derived macrophages, after 4 days in culture, also generated reduced oxygen species and eicosanoids in response to modified LDL. Along with our previous finding of scavenger receptor mediated lysosomal enzyme liberation, the present study indicates novel functions of these binding sites. Our observations may shed new light on the possible role of monocyte-macrophages in atherogenesis. PMID- 3090370 TI - Malnutrition and humoral immunity: long-term protein deprivation. AB - The effect of long-term protein deprivation and refeeding on delayed-type hypersensitivity (DTH) and humoral immune function was investigated in rats. Animals previously sensitized to keyhole limpet hemocyanin (KLH) were placed on a 2% protein diet ad lib for 8 weeks, after which some groups of animals were refed for up to 4 weeks. Control rats received normal rat chow. Recall skin testing with KLH, and immunization with tetanus toxoid (TT) were used to assess DTH and humoral immune responses. Weight, DTH, and antibody responses declined progressively with protein deprivation. Refeeding restored skin test responses and humoral immunity. There was a direct correlation between degree of malnutrition as reflected by weight and antibody responses as well as between DTH and antibody responses. The data demonstrate that chronic protein deprivation modulates both DTH skin testing and humoral immune responses and show that under conditions of altered immune function, there is a correlation between DTH responses and humoral immune function. PMID- 3090369 TI - The influence of serosal patch size on the growth of small intestinal neomucosa. AB - Several factors might affect the growth of neomucosa after serosal patching of small intestinal defects. Often only short segments of small intestine can be patched because of limited serosal surface and anatomic factors. The purpose of this study was to determine the influence of patch size on neomucosal growth. Twenty male New Zealand white rabbits underwent patching with colon serosa of either a 2 X 15-cm distal ileal defect (n = 10) or three 2 X 5-cm ileal defects (n = 10). There was significantly greater coverage of the patched defect by neomucosa in the triple patch group (99.4% vs 93.1% P less than 0.005) and significantly more of the smaller defects were completely covered by neomucosa than the larger defects (12 of 15 vs 0 of 5, P less than 0.05) at 8 weeks. The final area of the defect was 27.5 and 32.8% of the initial patched area respectively for the single and triple patches. Microscopically there was no difference in villous height or crypt depth, but crypt density was significantly greater in the triple group (207 +/- 11 vs 186 +/- 17 crypts/mm, P less than 0.05). In vitro glucose uptake and disaccharidase activity were similar in both groups. Patching multiple small intestinal defects results in more rapid neomucosal growth than a single large defect of the same surface area. This might be due to a greater circumference exposed to surrounding normal mucosa with a resultant increase in crypt density. Since function and villous development of the neomucosa are similar, multiple patches should result in a greater increase in absorptive capacity. PMID- 3090372 TI - Effect of cyclosporine on established islet autografts. AB - Cyclosporine (CyA) is toxic to the function of isolated islets and this toxicity may, in part, explain the failure of islet allografts as well as autografts with CyA immunosuppression. Not only do canine allografts fail despite CyA immunosuppression, but control autografts given CyA from the day prior to transplantation have a very high failure rate. In this study, we investigated CyA effects on established islet autografts. Twenty mongrel dogs underwent total pancreatectomy and successful intrasplenic islet autotransplantation. Ten served as control autografts (Group 1); five were started on oral CyA on the 5th postoperative day (Group 2) and 5 dogs were given CyA from the 10th day after grafting (Group 3). Intravenous glucose tolerance tests were performed before operation, before starting CyA and after 3 weeks. Plasma insulin was determined by radioimmunoassay. Control dogs remained normoglycemic throughout the study as did Group 3 animals. In Group 2, 2 of 5 dogs failed, both on the 4th day of CyA, while the other 3 were normoglycemic throughout the study. No significant difference was shown among the K values, fasting blood glucose and peak plasma insulin values following IVGTT before and after treatment with CyA. CyA begun the day before autografting gravely compromises graft success. However, after the graft is well established, an adverse effect of CyA on islet cell function is not evident. PMID- 3090371 TI - Effects of ibuprofen on a pig Pseudomonas ARDS model. AB - The effects of ibuprofen (I) were studied in the Pseudomonas (P) porcine ARDS model. Pigs, 14-26 kg (5 in each group), were anesthetized and ventilated with 0.5 FiO2 and 5 cm H2O PEEP. A control (C) group received saline only, a second group was given P, 1 X 10(8) org/ml at 0.3 cc/20 kg/min, and a third group was given P followed by 12.5 mg I at 20 and 120 min. Pulmonary arterial (PAP), wedge (PWP) and systemic arterial pressures, cardiac output (CO), and thermal cardiogreen extravascular lung water (EVLW), thromboxane (TxB2), 6-keto-PGF1 alpha, PaO2, PaCO2 were determined every 30 min. Albumin flux was measured with scintigraphic determination of lung:heart radioactivity ratios versus time, called slope index (SI). At 3 hr, P produced marked (P less than 0.05) increases in PAP (18 +/- 7 to 37 +/- 2 mm Hg), TxB2 (471 +/- 513 to 9216 +/- 3615 pg/ml), 6 keto-PGF1 alpha, EVLW (6.4 +/- 1.4 to 14.6 +/- 5.7 mg/kg), and SI (0.4 +/- 0.2 to 1.7 +/- 0.5 X 10(-3) U/min) with decreases in PaO2 (214 +/- 47 to 101 +/- 41 torr), CO and SAP. Ibuprofen caused a rapid clearing of TxB2 and 6-keto-PGF1 alpha associated with a transient decrease in PAP; PaO2 was considerably improved compared to P; however, CO, SAP, EVLW, and SI were unaffected. Prostaglandin blockage temporarily ameliorated the pulmonary hypertension and markedly improved oxygenation in this porcine septic ARDS model, but failed to alter increased permeability, confirming other studies that the increased pulmonary shunt in ARDS is not only dependent upon capillary leak. PMID- 3090373 TI - Effect of estradiol and progesterone on the rate of incorporation of radiolabeled arachidonate into phospholipids and triglycerides of the rat uterus. AB - To obtain information on the effect of estradiol (E) and progesterone (P) on the overall rate of the acylation and deacylation reactions with [3H]arachidonate ([3H]AA) in the rat uterus, we investigated the effect of chronic treatment of ovariectomized rats with 2-200 micrograms/day E-dipropionate (EPP) and with 2 mg P alone or with the combination of these steroids on the extent and the time course of the in vitro incorporation of [3H]AA into various phospholipids (PLs) and the triacylglycerol fraction (TG). The results demonstrate that physiologic doses of E leads to a rapid equilibrium of the deacylation-acylation cycle only in the case of phosphatidylinositol (PI) whereas at high (200 micrograms/day) dose level it exerts the same effect on phosphatidylcholine (PC), phosphatidylethanolamine (PE) as well as on TG. P alone has no remarkable effects in the ovariectomized rat, but it decreases markedly the incorporation of [3H]AA into PI and TG in intact animals. Furthermore, P decreases the incorporation of [3H]AA into PI in the ovariectomized rat treated with 2 micrograms/day EPP as well as attenuating the enhanced labeling of PC, PE and PI caused by higher doses. Time-course studies provide evidence that all of these effects of progesterone can be accounted for by its ability to decrease the rate of deacylation and, therefore, to prolong the time needed to attain equilibrium in the rates of acylation and deacylation reactions of the various lipids with arachidonate. These data offer a novel outlook on the regulatory role of progesterone and estrogens in uterine function. PMID- 3090374 TI - Hopf bifurcations and the stability of the respiratory control system. AB - A simple model of a feedback loop controlling ventilation is analysed. This model is intended to describe the response of the system, initially at equilibrium, to a sudden fall in CO2 concentration in the lung, brought about by a deep sigh. A previous paper described the model in detail and the general method of analysis. Here we continue the discussion of stability, first in terms of local stability after a small displacement from equilibrium and then by computer simulation to illustrate the behaviour after large displacements. The local analysis is used to select representative sets of system parameters to illustrate the different types of trajectory obtained by computer simulation. When the equilibrium point is stable the response to a disturbance is overdamped, underdamped or critically damped. When the equilibrium point is unstable the system responds by going into a limit cycle. The transition between these two cases proceeds via a Hopf Bifurcation. The limit cycle type of ventilatory pattern, i.e. a periodic, underdamped waxing and waning of ventilation is commonly seen in premature infants and in term infants between 1 and 6 months of age. PMID- 3090375 TI - Phenotype of thymic lymphomas in the mouse. AB - The MP2 cell line was established from a murine leukemia virus-induced thymic lymphoma. Half of the cells were consistently L3T4 positive and less than 5% of the cells were Lyt-2 positive. Single cell cloning on the basis of the presence or absence of Lyt-2 allowed the isolation of four clones with stable phenotypes: (1) Lyt-2-, L3T4-; (2) Lyt-2+, L3T4+; (3) Lyt-2-, L3T4+; (4) Lyt2+, L3T4-. These data are discussed in relation to tumour cell heterogeneity and to normal T-cell differentiation pathways. PMID- 3090376 TI - Identification of a major Leu 7/OKT 8 positive T-lymphocyte subpopulation in renal transplant patients pre-treated with total lymphoid irradiation. AB - When pretreated with total lymphoid irradiation, renal allograft recipients have an increased percentage of OKT 8 positive (cytotoxic/suppressor) T cells among their peripheral blood T lymphocytes (PBL) (56 +/- 21%) and also of Leu 7 PBL (47 +/- 18%). In contrast, transplant patients treated with azathioprine or cyclosporine A have percentages of OKT 8 and Leu 7 positive PBL, similar to control persons (respectively 29 +/- 13, 33 +/- 10, 30 +/- 10 for the OKT 8+ cells and 8 +/- 7, 11 +/- 6 and 15 +/- 9 for the Leu 7+ cells). After purification, about two thirds (70%) of the OKT 8 positive, OKT 3 positive, T lymphocytes of TLI patients were shown to co-express the Leu 7 antigen. It is concluded that after TLI, an increase of OKT 3+, OKT 8+ and Leu 7+ lymphocytes takes place, a subset previously described to be present in low numbers in control persons and whose function is still unclear. This expansion after TLI should allow functional identification of this subset and might contribute to the understanding of the immunosuppressive effects of TLI. PMID- 3090377 TI - Long-term care patient assessment. Evaluation of a methods effect. AB - Evaluation of a long-term care patient classification instrument in use in the Veterans Administration revealed that the levels of functional ability used in such instruments can influence their abilities to explain use of nursing time and reliability between raters. Specifically, a three-level scale that combines patients who require supervision with those who require help does not explain use of LPN and nurse's aide personal care time as well as does a four-level scale or a three-level scale that combines patients who require supervision with those who are independent. These findings should be considered in designing and applying patient assessment instruments. PMID- 3090378 TI - Inpatient length of stay in Twin Cities health plans. AB - In this paper we examine the relationship between inpatient length of stay and the patient's type of health insurance. The data consist of discharges in seven diagnosis-related groups (DRGs) from community hospitals in Minneapolis and St. Paul during 1982. After controlling for the effects of the patient's age, sex, medical condition, and severity of illness, as well as the hospital's size, teaching and ownership status, and average annual occupancy rate, we must reject the null hypothesis that the patient's type of health plan is unrelated to inpatient length of stay in Twin Cities community hospitals. We find that, in most cases, patients in prepaid group practices and independent practice associations exhibit significantly shorter lengths of stay than similar patients in Blue Cross and commercial health insurance plans, while Medicare and Medicaid patients exhibit significantly longer lengths of stay than those of similar commercially insured patients. PMID- 3090379 TI - Cost-effectiveness of the North Karelia Hypertension Program. 1972-1977. AB - The North Karelia Hypertension Program was initiated in 1972 as part of the North Karelia Project. This article examines the costs and effects of the first 5 years of the project. There were 288 fewer than expected fatal strokes and myocardial infarctions during the period; 134 of these are attributable to the hypertension program. The costs of the hypertension program totalled $5.16 million. Drugs consumed 86% of this cost. Using the zero discount rate as an outside boundary, the program is expected to increase old age pension costs by $2.5 million for the 5 years but will decrease earnings losses by $7 million for the same period. With earnings excluded, the cost per quality-adjusted life-year gained is $3,612 at zero discount and $5,830 at 10% discount. Hypertension care is more cost effective than many of the treatments applied after the appearance of coronary heart disease symptoms but would be much more cost-effective if hypertension could be treated as effectively without medications or if the costs of medications could be reduced. PMID- 3090380 TI - [Isolated bacteremia caused by Neisseria meningitidis type B]. PMID- 3090382 TI - Interferons in the treatment of chronic hepatitis B virus infection. AB - Hepatitis B virus offers several properties that may help to determine how antiviral substances, such as interferon, work. A description of the phases of chronic hepatitis B virus infection is presented, as well as the rationale for interferon therapy as treatment. PMID- 3090381 TI - [Disseminated gonococcal infection produced by penicillin-resistant gonococci]. PMID- 3090383 TI - Acute renal failure. AB - ARF is a common clinical problem associated with significant morbidity and mortality. Therefore, rapid and accurate diagnosis is imperative. Initial diagnostic strategies should be directed toward distinguishing among prerenal, renal, and postrenal causes of ARF. This can be done by the use of urinary diagnostic indices in concert with radiologic investigation, renal biopsy, and hemodynamic monitoring when appropriate. Treatment of established ARF should be directed toward maintaining fluid and electrolyte homeostasis and controlling complications resulting from retained nitrogenous waste products. This may necessitate the aggressive use of dialysis. As yet, there is no proven means to prevent ARF or alter the course of ARF once it is established. PMID- 3090384 TI - Endocrine emergencies. AB - Endocrine emergencies are relatively infrequent events in clinical practice. Correct management requires prompt recognition and treatment, frequent without supporting laboratory studies. An understanding of the pathophysiology of these acute states of hormone excess or deficiency assists in establishing the correct diagnosis and initiating the proper therapy. PMID- 3090385 TI - [Isolation of Pseudomonas aeruginosa products with immunotropic action]. PMID- 3090387 TI - [Sandfly fever--a 100-year-old viral disease hazardous to tourists visiting the Mediterranean]. PMID- 3090386 TI - Comparison of antimicrobial susceptibilities of Pseudomonas aeruginosa isolates, with and without plaques, from two hospitals. AB - Disc-agar diffusion plates, used for antimicrobial susceptibility testing, of 368 Pseudomonas aeruginosa isolates with and without plaques were compared. Seventeen percent of all isolates from the Veterans Administration Medical Center and eleven percent from Oklahoma Memorial Hospital produced plaques. When percentages of susceptibility for plaque and non-plaque containing isolates were compared, there were some statistically significant differences which are discussed in the text. PMID- 3090388 TI - [Histochemical studies of the denervated posterior cricoarytenoid muscle following direct long-term stimulation in an animal experiment]. AB - Histochemical evaluation (ATP-ase, NADH-Diaphorase, PAS) of the posterior cricoarytenoid muscle of the sheep was performed after long-term direct electrical stimulation to determine the changes of fibre type ratio and muscle metabolism. For comparison, histochemical results of a normal and a denervated, not stimulated posticus muscle are described. PMID- 3090389 TI - Effects at the periphery of the laser lesion in human brain and its tumors after CO2, Nd:YAG, and CO2 high-peak pulsed radiation. AB - The histological changes in various tissues irradiated with lasers are well known. Our own previous observations with the optical microscope confirm those already reported in the laser literature. If tissue is treated with various laser sources, the results are similar, with the characteristic three layers from the outside toward the inside of carbonization, coagulative necrosis, and edema. Otherwise, only the shapes and sizes of the lesions differ, with craters of different depths. In this paper, we report an ultrastructural study of the changes occurring in the periphery of the laser lesions in both normal human brain and neoplastic tissues (gliomas and meningiomas). Continuous-wave CO2 and Nd:YAG lasers were used at different exposure times and powers and the effects of high-peak pulsed CO2 laser radiation has also been investigated. The study, performed during neurosurgical procedures was mostly focused on microcirculation at 1.5-3 mm outside the area of coagulative necrosis, at the level of the edema zone. Only lesions of the blood brain barrier are produced in normal brain by CO2 radiation (power ranging from 40 to 80 W; exposure time from 3 to 10 seconds). The same results were achieved by Nd:YAG radiation of short duration (3 seconds) regardless of the power used (40 and 80 W). Long-duration Nd:YAG radiation (10 sec; power: 40-80 W) produces endoluminal phenomena leading to the complete occlusion of the capillaries. In neoplastic brain tissues, microcirculation does not seem to be impaired by CO2 radiation. More marked lesions are produced in tumors even after Nd:YAG short-time radiation. Endoluminal obliteration is observed in meningiomas and perivascular hemorrhage occurs in highly vascularized gliomas. According to these results, the risk of delayed post-operative hemorrhages, noticed in some patients with glioblastoma operated on by Nd:YAG lasers, suggests that residual tumor in the cavity should be treated by CO2 laser because of its minimal damage of microcirculation. PMID- 3090390 TI - Effect of CO2 laser irradiation on experimental fracture healing: a transmission electron microscopic study. AB - The healing of standardized fracture of rabbit radius was expedited as a result of treatment with low-power CO2 laser irradiation. Observation with transmission electron microscope revealed the following favorable effects of CO2 laser irradiation: The red blood cells were induced to disintegrate, thus promoting the absorption of the hematoma. The macrophages emerged early and increased in number so that debridement of the necrotic tissues was enhanced. The fibroblasts were more active in producing the fibrous callus. The chondrocytes were unusually active in forming bone tissues. The early and sustained appearance of osteoclasts favored the bone remodeling process. Increased capillary formation endowed the fracture healing with rich blood supply. Deposition of calcium salts took place early. PMID- 3090391 TI - Urologic dosimetry studies with the Nd:YAG and CO2 lasers: bladder and kidney. AB - Dose recommendations for the use of the Nd:YAG and CO2 lasers have been accepted with little laboratory analysis. We have examined both endoscopic and open applications in the bladder and open applications on the kidney with the lasers over a variety of power and pulse duration settings. In addition, we have studied the effect of varying the temperature of the tissue and irrigation solution on the depth of penetration. We found that with the Nd:YAG laser, the maximum depth of penetration in our animal model was only 2.62 mm in the bladder. This occurred during an endoscopic treatment with settings of 50 W at 4 seconds with irrigation solution of 25 degrees C. The depth of penetration using current recommendations of 40 W for 2 seconds was less than 1 mm at all temperatures. Room temperature irrigation solution may be the ideal compromise, but higher-power long-pulse durations or repeated treatments to the same area may be necessary to achieve penetrations of 3-5 mm. In open applications on bladder and kidney, the maximum depth of penetration in our animal model was 2.75 mm, which was found during a treatment with settings of 60 W at 4 seconds with the kidney parenchyma at 25 degrees C. Using the CO2 laser on open applications of bladder strips, we obtained a maximum depth of penetration of 1.75 mm at 30 W of power for 1/2 second at 85 degrees C tissue temperature. Unfortunately, penetration by the CO2 laser is accompanied by vaporization of tissue, leaving a large crater. Minimal injury exists beyond this area. In the kidney, we obtained a maximum depth of penetration of 1.75 mm at 30 W of power at 25 degrees C and 20 W of power at 2 degrees C each for 1/2 second. PMID- 3090392 TI - Laryngo-tracheal laser surgery and general anesthesia. AB - The use of the carbon dioxide laser in treatment of laryngo-tracheal lesions is extremely effective when combined with general anesthesia. However, the potential for intraoperative complication is increased due to a pathological reduction in the size of the airway and the presence of an endotracheal tube. To avoid the hazard of endotracheal tube ignition, specific techniques are employed. PMID- 3090393 TI - Sensitivity of anterior pituitary hormones to graded levels of psychological stress. AB - The effect of graded levels of stressor intensity on anterior pituitary hormones was studied in adult male rats. Corticosterone, considered as a reflection of ACTH release, and prolactin responses showed a good correlation with the intensity of the stressors. On the contrary, neither LH, GH nor TSH release showed a parallelism with the intensity of the stressors in spite of the fact that they clearly responded to all the stimuli. It appears that the hormones of the anterior pituitary might be divided into two groups: those whose response is sensitive to the levels of emotional arousal elicited by stress, and those displaying a clear but stereotyped response during stress. However, other alternative explanations might exist to justify the present results. The neural mechanisms underlying the two types of response are at present unknown. These data indicate that only the pituitary-adrenal axis and prolactin have some potential utilities as quantitative indices of emotional arousal elicited by currently applied stressors in the rat. PMID- 3090394 TI - Chronic treatment with bromocriptine induces behavioral supersensitivity in rats. AB - Chronic treatment of rotating rats with equipotent doses of the dopamine (DA) agonists apomorphine (APO), 3-(3,4-dihydroxyphenyl)-1-n-propylpyrrolidine hydrobromide (DPPP) and bromocriptine (BRO) for four weeks resulted in marked differences in rotational activity following acute administration of these agonists. Whereas chronic treatment with APO and DPPP failed to produce any significant changes in agonist-induced rotational behavior, chronic BRO treatment induced a progressive increase in rotational activity up to a mean 200% increase over controls at four weeks. These findings may, in part, explain the long-term clinical efficacy of bromocriptine in patients with Parkinson's disease. PMID- 3090395 TI - Indirect stimulation by thyrotropin-releasing hormone of canine gallbladder motility. AB - Thyrotropin-releasing hormone (TRH) was unable to induce any noticeable contraction of canine isolated gallbladder strips up to the dose of 10(-4) g/ml, while caerulein (CAER) was spasmogenic in a dose-related manner beyond 10(-11) g/ml. This effect of CAER was unaffected by either atropine or tetrodotoxin. In conscious dogs, the intravenous bolus of TRH (20 micrograms/kg) or CAER (0.2-2.0 micrograms/kg) caused gallbladder emptying. The TRH response, unlike that of an equipotent dose of CAER, was prevented by atropine. In experiments on electrical activity of the digestive tract in conscious dogs, both TRH or CAER induced a concomitant increase on the myoelectrical activity in the proximal part of the small intestine. The excitatory effects were prevented by atropine only in the case of TRH. These results demonstrate that TRH stimulates indirectly the gallbladder and proximal duodenum of the dog. They suggest the involvement of a cholinergic pathway in this excitatory action. PMID- 3090396 TI - Inhibition of mammalian digestive disaccharidases by polyhydroxy alkaloids. AB - Several polyhydroxy alkaloids, including the eight presently known to occur in plants, have been compared as inhibitors of mouse gut digestive disaccharidases. The indolizidine castanospermine inhibited all activities tested, but others showed a selectivity which could be of value in studies of carbohydrate digestion and errors of metabolism. PMID- 3090397 TI - A comparison of the effects of suckling or transient dopamine antagonism on thyrotropin-releasing hormone and suckling induced prolactin release in lactating rats. AB - Prolactin (PRL) release was studied in mid-lactational female rats by comparing the stimulatory influence of suckling to a drug protocol that mimics the effect of suckling on the anterior pituitary (AP). Animals that nursed pups for 15 minutes and were allowed to suckle again 60 minutes later for 10 minutes, released PRL effectively during both nursing episodes; however, in animals that received the dopamine (DA) agonist 2-Br-alpha-ergocryptine maleate (CB-154, 0.5 mg/rat i.v.) at the end of the first nursing period did not show an increase in plasma PRL to a second suckling stimulation by the pups. When thyrotropin releasing hormone (TRH) was substituted for the second suckling period in CB-154 treated rats, a slight increase in plasma PRL occurred 5 minutes after the injection. In a third study we transiently blocked the action of DA at the AP by injecting the DA antagonist domperidone (0.01 mg/rat i.v.), followed 5 minutes later by the administration of CB-154. One hour later animals were either allowed to suckle pups for 10 minutes or were injected with TRH. Treatment with TRH resulted in an 11 fold increase in plasma PRL but suckling was completely ineffective in inducing PRL release. These data suggest that the lack of PRL release to suckling in CB-154 treated rats was due to inhibitory effects of CB 154 on neural mechanisms which link nursing to PRL release. In addition, the data show that pharmacologic DA antagonism affects TRH releasable PRL more than does suckling. This may be due to a reduction, by suckling, of the pool of PRL that is available to be released by TRH administration. PMID- 3090398 TI - Enhanced luminescence: application in a photographically monitored enhanced luminescent enzyme immunoassay for factor VIII related antigen. PMID- 3090399 TI - Microplate blood grouping with computer-controlled reading and data interpretation. PMID- 3090400 TI - Inappropriate major histocompatibility complex class II expression by thyroid follicular cells in thyroid autoimmune disease and by pancreatic beta cells in type I diabetes. AB - "Inappropriate" expression of class II major histocompatibility complex (MHC) molecules by target cells has been found in all organ-specific autoimmune diseases so far examined for the presence of this phenomenon. These glycoproteins may have a functional role as class II+ thyrocytes are able to present both small fragments of foreign antigens and autoantigens to helper T cells. Interferon gamma is a likely modulator of MHC class II expression in the thyroid but other signals like thyroid-stimulating hormone seem to influence its action. By contrast, it appears that lymphokines are not involved in inducing the inappropriate MHC class II expression observed in situ in the pancreatic beta cells of diabetics. These data suggest that regulation of MHC class II expression is different in thyroid follicular cells from pancreatic beta cells, and that similar differences may be found in other cell types involved in autoimmune disease, thus reinforcing the concept of heterogeneity in the pathogenesis of organ-specific autoimmune disorders. PMID- 3090402 TI - Inhibition of transformation of Bacillus subtilis by ethidium bromide. AB - Incubation of donor DNA with ethidium bromide before addition to competent cells, strongly inhibited chromosomal transformation, plasmid transfer and phage-SPP1 DNA mediated transfection. There was no effect of the dye on the binding and entry of DNA into the cells. Analysis of the fate of transforming DNA treated with ethidium bromide showed a reduction in the amount of donor DNA associated with the recipient chromosome. The formation of this donor-recipient complex seems to be slowed down by the dye. PMID- 3090401 TI - Cloning of cDNA coding for human tissue-type plasminogen activator and its expression in Escherichia coli. AB - cDNA clones of the mRNA coding for tissue-type plasminogen activator (t-PA) have been obtained and their nucleotide sequences compared to those reported previously. A gene coding for t-PA has been reconstructed and inserted into vectors for expression in prokaryotic cells. Relatively high levels of t-PA accumulated in inclusion bodies in Escherichia coli containing an optimized expression plasmid, but only a small proportion of the insoluble protein was recovered as active enzyme using a variety of solubilization procedures. PMID- 3090403 TI - Influence of caffeine on mitomycin C induced mutagenesis. AB - Caffeine significantly repressed MMC induced reversion of Salmonella typhimurium strain TA92 from his- to his+. The addition of MMC (0.5 micrograms/ml) to broth cultures resulted in a slightly decreased growth rate, as measured turbidimetrically, along with a linear decline in CFU of 1 log cycle in 7 h. The addition of caffeine (0.33 mg/ml) plus MMC (0.5 micrograms/ml) resulted in cessation of growth and a decrease in culture turbidity after two generations of growth which was accompanied by a linear decline in CFU of four log cycles in 7 h. The repression of MMC induced mutagenesis by caffeine is therefore most probably due to interference with an error-prone repair process which results in the destruction of cells with damaged DNA. PMID- 3090404 TI - The effects of transmural transport in the microcirculation: a two gas species model. AB - Diffusion of oxygen and carbon dioxide across the walls of noncapillary vessels in the microcirculation has been suggested by several studies. The formulation and steady-state solutions to a nine-compartment mathematical model of the microcirculation of skeletal muscle with transmural gas diffusion in all vessels are presented. The simultaneous transport of oxygen and carbon dioxide between arterioles, capillaries, and venules, and connective and muscle tissue at rest and exercise are described. Special attention is paid to the interactions of these gases in blood. This model predicts a longitudinal intravascular gradient in oxygen tension from large to small vessel with the tension at the precapillary vessels relatively insensitive to changes in the input tension. At rest, there is significant small arteriolar oxygen flux. However, during exercise, the precapillary transmural flux of oxygen is only a small fraction of the total metabolic demand. The model predicts large noncapillary fluxes of carbon dioxide, and also that tissue PCO2 is dependent on input tensions. The model also predicts that Bohr shifts due to either changes in input PCO2 or increased precapillary PCO2 due to increased metabolism may cause physiologically significant changes in precapillary PO2. Countercurrent shunting was predicted by the model to be significant only for carbon dioxide. PMID- 3090405 TI - Chlamydial ophthalmia neonatorum. PMID- 3090406 TI - From prions to prionic viruses. AB - The pathogens causing scrapie and other similar degenerative neurological diseases are called "prions" and classified either as viruses or, more often, as a novel class of pathogens. It is argued herein that prions are not the pathogens producing these diseases. The pathogens involved are endogenous viral systems inherited by the host. These endogenous parasites, tentatively named prionic viruses, produce the prions which are horizontally transmitted. The prions trigger the pathological manifestation of prionic viruses. PMID- 3090408 TI - Severity of illness and Diagnosis Related Groups. PMID- 3090407 TI - A common structural pattern among many biologically active compounds of natural and synthetic origin. PMID- 3090409 TI - The dependence of mass energy absorption coefficient ratios on beam size and depth in a phantom. AB - The Monte Carlo computer code "electron gamma shower" (EGS) has been used to determine photon spectra in a water phantom. Spectra used by Johns and Cunningham and for the AAPM dosimetry protocol have been used as input data and ratios of average mass energy absorption coefficients have been calculated for a number of depths and field sizes. The results show that there is a slight dependence on both of these parameters. For example, (mu en/P) water graphite for cobalt-60 varies from a value of 1.111 for the primary spectrum in air, to 1.135 at a depth of 20 cm in a phantom for a beam approximately 1 m2 in area. This variation of over 2% is relevant for dosimetry. The variation is less than this for high energy radiation beams and in most cases can be ignored. The effect is greater for high atomic materials such as bone, where the range of variation of (mu en/P)bone water, again for cobalt radiation, may be as great as 15%. This too is less for high-energy bremsstrahlung spectra. PMID- 3090410 TI - Calculation of photon dose distributions in an inhomogeneous medium using convolutions. AB - A formulation of the single energy photon transport problem is cast in the form of a series of convolutions over the primary fluence distribution with invariant kernels. A method is developed for compensating for the variant intervoxel attenuation in the scattered dose distribution by means of an invariant correction kernel. Results of applying the formulation to 60Co distributions in the presence of slab and block inhomogeneities are presented. PMID- 3090411 TI - Characteristics of electron beams from a medical microtron. AB - The Instrument AB Scanditronix MM22 medical microtron provides ten electron beam energies from approximately 3 to 22 MeV. Isodose curves, depth dose curves, field uniformity, and other characteristics were measured in water and in polystyrene. The method of acceleration, dual scattering foil system, and collimation technique produce beams having features superior to many other medical electron accelerators. Maximum dose rates at isocenter varied from about 500 to over 900 cGy min-1, photon contamination from 0.6% to 4.1%, and surface doses from 70% to 95% of the maximum. Depth dose curves were indistinguishable from those with identical practical ranges of a scanned beam linac at energies less than 18 MeV, and field flatness was clearly superior to the scanned beam linac at standard treatment distances. PMID- 3090413 TI - [Neonatal colonization by Pseudomonas aeruginosa. Results of 2 1/2 years of surveillance at the Isernia Hospital]. PMID- 3090412 TI - Spinal axis irradiation with electrons: measurements of attenuation by the spinal processes. AB - Electrons may be used beneficially for spinal axis irradiation in medulloblastoma children to avoid some of the long-term sequelae induced by megavoltage photons. However, the attenuation by the intervening bone ought to be considered. Three dimensional computer treatment planning with inhomogeneity correction for electron beams is not yet generally available, and alternate methods are needed to evaluate the attenuation by the complex bony structure of the spine. Here, we present our experimental data showing the alteration in the electron isodoses due to the intervening spinous processes. Film dosimetric measurements were made in the vertebral columns obtained from autopsies of a goat, a dog, and a child. Our results show that electron beam therapy for the spinal axis is a viable option. PMID- 3090414 TI - King for a day: or, dreams of being old. PMID- 3090415 TI - Hepatitis B among parenteral drug abusers--North Carolina. PMID- 3090417 TI - Release of botulism antitoxin. PMID- 3090416 TI - Acute respiratory illness following occupational exposure to wood chips--Ohio. PMID- 3090418 TI - Aedes albopictus infestation--United States, Brazil. PMID- 3090419 TI - Decrease in lung cancer incidence among males--United States, 1973-1983. PMID- 3090420 TI - Standardization and evaluation of the clinical usefulness of mycobacterial skin test antigens. PMID- 3090421 TI - Cigarette smoking among public high school students--Rhode Island. PMID- 3090422 TI - Deaths due to chronic obstructive pulmonary disease and allied conditions. PMID- 3090423 TI - Antigenic variation of recent influenza A(H1N1) viruses. PMID- 3090424 TI - Monovalent influenza A(H1N1) vaccine, 1986-1987. PMID- 3090425 TI - Measles--United States, first 26 weeks, 1986. PMID- 3090426 TI - Occupational fatality following exposure to hydrogen sulfide--Nebraska. PMID- 3090428 TI - Hepatic synthesis of apolipoprotein AI in rats with nephrotic syndrome. Changes in hepatic mRNA for ApoAI. PMID- 3090427 TI - Genetic polymorphisms and atherosclerosis. PMID- 3090429 TI - An oral fat tolerance test: preliminary results. PMID- 3090430 TI - Cerebral blood flow tomography by single photon emission computerized tomography using 133Xe in cerebrovascular disease. PMID- 3090431 TI - Quantitative freeze-fracture studies of membrane changes in chicken muscular dystrophy. AB - Muscular dystrophy induces extensive changes in the patterning of sarcolemmal caveolae of fast-twitch fibers from the chicken posterior latissimus dorsi (PLD) muscle, which in healthy fibers are arranged in striking bands over the myofibrillar I-bands. In dystrophic fibers the caveolae lack this patterned arrangement, and instead are dispersed over the entire sarcolemma, are irregular in shape, and are more numerous in older birds. Quantitative analysis of these differences provides three independent numerical indices of the dystrophic state and suggests that constraints responsible for normal patterning are lost in diseased fibers. These observations support theories that defects of the muscle plasma membrane are important for dystrophic pathogenesis. In contrast, the sarcolemma of slow tonic fibers from anterior latissimus dorsi (ALD) and metapatagialis latissimus dorsi (MLD) muscles have randomly dispersed caveolae whose appearance and distribution are unaffected by the disease. PMID- 3090432 TI - Developmental study of alpha-glucosidases in Japanese quails with acid maltase deficiency. AB - In Japanese quails with late-onset acid maltase deficiency (AMD), the activity of acid alpha-glucosidase was severely reduced to approximately 16% of the normal level from an embryonic age. The kinetic characteristics and inhibition by Zn indicated that the residual activity was responsible for the intrinsic activity of acid alpha-glucosidase. However, in affected embryos, the glycogen content and other lysosomal enzyme activities were normal, despite the low acid alpha glucosidase activity. In a separate study, we found the existence of two age dependent neutral alpha-glucosidases--"embryonic" and "adult" alpha-glucosidases. In affected quails, the transition from the embryonic neutral alpha-glucosidase to the adult type was not influenced by the disease. The activity toward maltose and glycogen of the embryonic neutral alpha-glucosidase may explain the normal glycogen content in the affected embryos. PMID- 3090433 TI - Polyamine biosynthesis in trichomonads. AB - Trichomonas vaginalis, Tritrichomonas foetus and Trichomitus batrachorum grown in modified Diamond's medium all had high concentrations of putrescine and lower concentrations of spermidine and spermine. Ornithine decarboxylase (ODC; EC 4.1.1.17) was detectable in all three species although at significantly different levels. Trichomonas vaginalis had the highest activity (typically around 1.85 nmol min-1 (mg protein)-1), Trichomitus batrachorum the lowest (0.11 nmol min-1 (mg protein)-1). The Trichomonas vaginalis ODC had an apparent Mr of 230 000 and was severely inhibited by alpha-difluoromethylornithine (DFMO). S-Adenosyl methionine decarboxylase (EC 4.1.1.50) could not be detected in T. batrachorum but was present in the other two species. Arginine decarboxylase was apparently absent from all three. All three trichomonad species were able to accumulate spermidine and putrescine from the medium. When T. vaginalis was grown in the presence of DFMO (4 mM), which had little effect on parasite growth, ODC activity was reduced by over 99% and the polyamine content was altered; putrescine concentrations were decreased, those of spermidine and spermine remained the same or were raised. DFMO-treated cells accumulated more exogenous putrescine than untreated control cells. The results suggest that the lack of effect of DFMO on T. vaginalis in culture was due to the parasite being able to accumulate polyamines from the growth medium. It appears, therefore, that testing DFMO and similar compounds in axenic trichomonad cultures may well not give a true indication of their effectiveness in vivo where sources of exogenous polyamines may not be available. PMID- 3090434 TI - Trypanosoma cruzi: polypeptide markers of epimastigotes and trypomastigotes. AB - We compared the major polypeptides of epimastigotes and trypomastigotes of T. cruzi, by submitting total parasite lysates to electrophoresis in polyacrylamide gels (SDS-PAGE), protein staining with Coomassie brilliant blue, laser densitometry, or immunoblotting with sera derived from infected individuals (Chagas' disease). Epimastigotes and trypomastigotes displayed extensive homology, the differences being quantitative, except for a trypomastigote specific band of Mr 75,000 which reacted with chagasic sera. Immunoblotting with chagasic sera confirmed the electrophoretic homology of epimastigotes and trypomastigotes. Upon antigenic dilution, a cluster of antigenic bands in the range of Mr 150,000 to 75,000 prevailed in the trypomastigotes, whereas the epimastigotes displayed more abundance of antigenic bands in the range of Mr 72,000 to 36,000. PMID- 3090435 TI - Anaerobic pyruvate metabolism of Tritrichomonas foetus and Trichomonas vaginalis hydrogenosomes. AB - Hydrogenosomes isolated from Tritrichomonas foetus and Trichomonas vaginalis fermented pyruvate to acetate, malate, H2, and CO2 in an anaerobic process dependent on ADP, Pi, Mg2+, and succinate. The extent to which pyruvate was carboxylated to malate by malate dehydrogenase (decarboxylating) rather than decarboxylated to acetate by pyruvate/ferredoxin oxidoreductase was dependent on pCO2. The processes observed showed carbon and redox balances. The presence of an NADH/ferredoxin oxidoreductase activity was demonstrated. This enzyme is likely to be involved in the transfer of electrons from the ferredoxin reduced in pyruvate oxidation to NAD+ needed for the reductive carboxylation of pyruvate. Disruption of hydrogenosomes with Triton X-100 led to cessation of pyruvate dependent H2 formation which could be restored by addition of coenzyme A and methyl viologen or ferredoxin. The formation of acetate and H2 by undisrupted hydrogenosomes proceeded at approximately half maximal rates in the presence of 25 microM succinate for T. foetus and 5 microM succinate for T. vaginalis. The apparent Km value of the acetate/succinate CoA transferase from T. foetus for succinate was approximately 45 microM, thus the stimulating effect of succinate might be due to the requirement of this enzyme for succinate. The exact mechanism of this effect remains to be elucidated, however. PMID- 3090436 TI - The pathogenesis of atherosclerosis--and an exchange on research support by the tobacco industry. PMID- 3090438 TI - Ultrasonographic fetal surveillance in the management of the isoimmunized pregnancy. AB - During the past 20 years the management of pregnancies involving rhesus sensitization has been based on determinations of the optical density of amniotic fluid as an index of the bilirubin concentration and the degree of hemolysis. High values have dictated intervention in the form of delivery or intrauterine transfusion, depending on the gestational age. Since 1982 intensive surveillance with ultrasound imaging and electronic monitoring of the fetal heart rate have become useful in decisions about the timing of intervention. Using these tools, we followed 11 fetuses who would previously have been treated by multiple intrauterine transfusions or early delivery, for 8 to 63 days without treatment. All were born alive, in good condition and without hydrops, at gestational ages of 30.5 to 36.0 weeks. The lengths of stay for the neonates ranged from 8 to 48 days, and all were discharged alive. We conclude that rhesus sensitization in a select group of fetuses, who according to former standards would have been candidates for earlier delivery or intrauterine transfusion, can be managed expectantly for longer periods by careful observation with modern techniques of surveillance. PMID- 3090439 TI - Medicine and health care in South Africa. PMID- 3090437 TI - Decreased hypothalamic gonadotropin-releasing hormone secretion in male marathon runners. AB - Hypogonadotropic hypogonadism due to a deficiency in hypothalamic gonadotropin releasing hormone is common in female athletes ("hypothalamic amenorrhea"). It is not known, however, whether a similar phenomenon occurs in male athletes. We investigated the integrity of the hypothalamic-pituitary-gonadal axis in six highly trained male marathon runners (who were running 125 to 200 km per week). The mean (+/- SEM) frequency of spontaneous luteinizing hormone pulses was diminished in the runners, as compared with healthy controls (2.2 +/- 0.48 vs. 3.6 +/- 0.24 pulses per eight hours, P less than 0.05). The amplitude of the pulses was also low in the runners (0.9 +/- 0.24 vs. 1.6 +/- 0.15 mlU per milliliter; P less than 0.05), and the responses of luteinizing hormone to gradually increasing doses of exogenous gonadotropin-releasing hormone were decreased. Plasma testosterone levels were similar in the two groups and increased equally in response to an intramuscular injection of 2000 units of human chorionic gonadotropin. During short-term intense physical exercise (a treadmill run at 72 percent of maximal oxygen consumption for two hours), the plasma gonadotropin levels in the athletes remained stable, but significant elevations in plasma levels of cortisol, prolactin, and testosterone occurred. We conclude that highly trained male athletes, like their female counterparts, may have a deficiency of hypothalamic gonadotropin-releasing hormone. This condition may be caused by the prolonged, repetitive elevations of gonadal steroids and other hormones known to suppress gonadotropin-releasing hormone secretion that are elicited by their daily exercise. PMID- 3090441 TI - The PHS Task Force on Women's Health Issues. PMID- 3090440 TI - [Maintenance of intravenous hyperalimentation at home--challenge to the terminal care which is satisfactory to the patient]. PMID- 3090442 TI - Clinical investigations of drug effects in women. PMID- 3090443 TI - Drug use patterns and premenstrual dysphoria. PMID- 3090444 TI - Drugs and drug interactions in the elderly woman. PMID- 3090445 TI - Gender and the teenage smoker. PMID- 3090447 TI - FDA's perspective on women and drugs. PMID- 3090446 TI - Gender differences in drug use: an epidemiological perspective. PMID- 3090448 TI - Thyrotrophin-releasing hormone. New applications in the clinic. PMID- 3090449 TI - The inducible cytotoxic T-lymphocyte-associated gene transcript CTLA-1 sequence and gene localization to mouse chromosome 14. AB - Classical phenomenological approaches to the study of the mechanism of T-cell mediated cytotoxicity have now given way to a search for molecules involved in this function; this is attempted either by subcellular and biochemical fractionation of material from cytotoxic cells, or through the characterization of molecules recognized by cytotoxicity-inhibiting monoclonal antibodies Molecules having a role in cytotoxicity may also be identified by detecting the corresponding messenger RNA transcripts. Such an approach may include, as a first step, the search for transcripts as specific as possible to cytotoxic T cells; only secondarily can their actual relevance to cytotoxicity be investigated. We report here the preparation and systematic screening of a differential complementary DNA bank, in which we detected three distinct messenger RNA transcripts (CTLA-1, CTLA-2 and CTLA-3) present in various cytotoxic T cells but not (or less so) in a range of non-cytotoxic lymphoid cells. We describe the co inducibility of these transcripts and of cytotoxicity in thymocytes and hybridoma cells, the sequence of CTLA-1 cDNA, its protein homology with serine esterases and the localization of the corresponding gene to mouse chromosome 14. PMID- 3090450 TI - Homology between IgE-binding factor and retrovirus genes. PMID- 3090451 TI - Capacity of purified Lyt-2+ T cells to mount primary proliferative and cytotoxic responses to Ia- tumour cells. AB - Allogeneic gene products of the major histocompatibility complex, the HLA complex in man and the H-2 complex in mice, induce T lymphocytes to exert powerful mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML). In mice, the subset of T cells carrying the L3T4 surface antigen but lacking the Lyt-2 antigen responds predominantly to H-2 class II (Ia) differences whereas the L3T4- Lyt-2+ subset reacts to class I (K/D) differences. For primary responses the stimulus for MLR and CML appears to be controlled by Ia+ cells of the macrophage/dendritic cell lineages, for both L3T4+ and Lyt-2+ cells. The finding that Ia+ cells are required for responses involving Lyt-2+ cells has been taken to imply that triggering of these cells is controlled by Ia-restricted L3T4+ cells. Lyt-2+ cells have thus come to be regarded as crippled cells which are heavily dependent on 'help' from other T cells. This well-entrenched view is challenged by evidence presented here that purified Lyt-2+ cells can give high primary responses to certain Ia- tumour cells in vitro. PMID- 3090452 TI - An analgesic effect of enkephalinase inhibition is modulated by monoamine oxidase B and REM sleep deprivations. AB - Both the MAO-B inhibitor deprenyl (2.5-10 mg/kg, ip, 60 min prior) and the MAO-B substrate beta-phenylethylamine (PEA, 40 micrograms, icv) potentiated the analgesic action of the enkephalinase inhibitor phosphoramidon (250 micrograms, icv) in animals allowed normal sleep. The enhancing effect of PEA on phosphoramidon analgesia was further potentiated by deprenyl (5 mg/kg, ip) pretreatment. Deprenyl (5 mg/kg, ip) or PEA (40 micrograms, iv) given alone did not induce analgesia in animals allowed undisturbed sleep. REM sleep deprivation (REMSD) decreased the basal pain threshold and abolished the analgesic effect of phosphoramidon. The administration of deprenyl and/or PEA failed to restore the analgesic effect of phosphoramidon in REM sleep deprived animals. The results indicate that excess PEA has a stimulatory effect on the analgesic activity of endogenously released enkephalins in rats allowed undisturbed sleep but not in REM sleep deprived animals. It is suggested that the failure of phosphoramidon to induce analgesia after REMSD, is probably due to a functional insufficiency of an enkephalinergic system. PMID- 3090453 TI - Inhibition of endothelium-dependent smooth muscle relaxation by calmodulin antagonists. AB - By using the calmodulin antagonists, calmidazolium and N-(6-aminohexyl)-5-chloro 1-naphthalene-sulfonamide (W-7), the hypothesis was investigated as to whether calmodulin is involved in the sequence of events leading to the endothelium dependent vascular smooth muscle relaxation. Endothelium-dependent relaxations were studied on two different preparations, the rabbit aorta and the pulmonary artery of the guinea pig. Relaxations were produced in the precontracted rings (noradrenaline 3 X 10(-6) mol/l) in response to acetylcholine, 10(-8) to 10(-6) mol/l (aorta), histamine, 3 X 10(-8) to 1 X 10(-6) mol/l (pulmonary artery) or the calcium ionophore A 23187, 1 X 10(-8) to 3 X 10(-7) mol/l (aorta and pulmonary artery). In the presence of calmidazolium and W-7 the endothelium dependent relaxation was inhibited in a dose dependent manner. This inhibition was seen in a concentration range that coincides with calmodulin inhibition. The half maximal concentrations of calmidazolium for the inhibition of the relaxation of the aorta induced by acetylcholine and A 23187 were 3 X 10(-6) mol/l and 1.4 X 10(-6) mol/l and that of W-7 were 3.1 X 10(-5) and 3.6 X 10(-5) mol/l, respectively. Complete inhibition was obtained both for acetylcholine-and for A 23187-induced relaxations by preincubation with 1 X 10(-5) mol/l calmidazolium or 1 X 10(-4) mol/l W-7. The half maximal concentrations of calmidazolium for the inhibition of the relaxation of the pulmonary artery in response to histamine and A 23187 were 2.7 X 10(-6) mol/l and 3 X 10(-6) mol/l and complete inhibition was achieved at 1 X 10(-5) mol/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090454 TI - Role of guanine nucleotide-binding protein in the regulation by adenosine of cardiac potassium conductance and force of contraction. Evaluation with pertussis toxin. AB - In atrial cardiac preparations adenosine exerts a receptor-mediated negative inotropic effect due to an increased potassium conductance. Pretreatment of guinea pigs with pertussis toxin abolished the negative inotropic and action potential shortening effect of adenosine and the adenosine analogue (-)-N6 phenylisopropyladenosine (PIA). As pertussis toxin specifically inactivates guanine nucleotide-binding proteins involved in the signal transfer from receptor binding to specific cell functions, it is concluded that a guanine nucleotide binding protein is involved in the regulation of the receptor-mediated change in potassium conductance and force of contraction. PMID- 3090456 TI - Focal motor seizures in a thirsty man. PMID- 3090455 TI - Reversal of the effect of centrally-administered diazepam on morphine antinociception by specific (Ro 15-1788 and Ro 15-3505) and non-specific (bicuculline and caffeine) benzodiazepine antagonists. AB - Diazepam, injected into the lateral ventricles reduced the antinociceptive effect of morphine in rats, as measured by the tail-flick method. Specific antagonists of diazepam (Ro 15-1788 and Ro 15-3505) had no effect themselves but prevented inhibition by diazepam of morphine antinociception. Furthermore, the action of diazepam was partially reversed by intracerebroventricular injection of bicuculline or caffeine. These findings support the view that the depressant effect of diazepam on morphine antinociception is specific and GABAergic in nature and that some actions of diazepam are also mediated via the purinergic system. PMID- 3090458 TI - [Preoperative parenteral feeding in malnutrition: useful or useless?]. PMID- 3090459 TI - [Rhesus antagonism]. PMID- 3090457 TI - The cost-effectiveness of nurse practitioners. PMID- 3090460 TI - Genetic background of high incidence of spontaneous tumors in BDX rats. AB - Genetic background of high incidence of spontaneous tumors in BDX rats was investigated with respect to susceptibility to physical or chemical agents and immune response. Percentages of colony forming ability of normal embryo fibroblasts from BDX rats after exposure to various doses of ultraviolet (UV) light, X-rays and Mitomycin C were almost identical to those of cells from control F344 rats. Furthermore, BDX rats showed similar level of rosette forming cells, blastogenic response, and plaque forming cell (PFC) response as compared with WKA rats used as a control, although BDX rats showed higher natural killer (NK) cell activity. These results indicate that high incidence of spontaneous tumors in BDX rats is not due to some defects in DNA repair or immune response. In 3 methylcholanthrene (MCA) carcinogenesis, however, BDX rats developed tumors very early; the mean latency periods for development of MCA-induced tumors were 135 days in BDX rats and 256 days in F344 rats. Measurement of the inducibility of specific aryl hydrocarbon hydroxylase (AHH) activity in liver microsomes revealed that BDX rats showed higher inducibility than F344 rats: the inducibilities were 23.7 in BDX rats and 5.7 in F344 rats. Higher inducibility of AHH in BDX rats seemed to be parallel to earlier development of tumors in MCA carcinogenesis in the rats. Thus, it is most likely that high incidence of spontaneous tumors in BDX rats is due to high susceptibility to some chemical carcinogens which may be contained in foods or drinking water in a small dose. PMID- 3090461 TI - DDAVP, cryoprecipitate, and highly 'purified' factor VIII concentrate in uremia. PMID- 3090463 TI - The rapid 'tonic' and the delayed 'induction' components of the prolactin-induced activation of tuberoinfundibular dopaminergic neurons following the systemic administration of prolactin. AB - The present study was designed to characterize the time and dose relationships of the response of tuberoinfundibular dopaminergic (TIDA) neurons in the rat to systemically administered prolactin (PRL). The activity of TIDA neurons was estimated by measuring the rate of dopamine (DA) synthesis in the median eminence (DOPA accumulation following the administration of a decarboxylase inhibitor). Rats were pretreated with bromocriptine, a dopaminergic agonist, so as to inhibit the release of endogenous PRL from the anterior pituitary, and thereby reduce the activity of TIDA neurons to a 'basal' level from which it could be increased subsequently by exogenously administered PRL. In control animals an intraperitoneal injection of ovine PRL (oPRL) increased DOPA accumulation at 16 h, but not before, whereas in bromocriptine-pretreated animals an intraperitoneal injection of oPRL increased DOPA accumulation after 4 h ('tonic' component) and caused a further increase after 16 h ('induction' component). Continuous intravenous infusions of oPRL into bromocriptine-pretreated rats increased DOPA accumulation in the median eminence by 4 h, and when infused into control rats oPRL reduced serum concentrations of endogenous rat PRL (rPRL) by 2 and 4 h. Continuous intravenous infusions of rPRL increased DOPA accumulation in the median eminence after 2 h; this effect exhibited a very steep dose-response relationship (possibly an 'all-or-none' response). TIDA neurons were very sensitive to changes in circulating concentrations of PRL; their activity was increased if serum PRL concentrations were merely doubled by infusing a low concentration of rPRL for 4 h. Three daily injections of haloperidol elevated circulating rPRL concentrations and increased the rate of DOPA accumulation in the median eminence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090462 TI - Gonadotropin secretion following intraventricular norepinephrine infusion into neonatally androgenized female rats. AB - To determine whether norepinephrine (NE) will stimulate gonadotropin secretion in androgenized female rats, we administered NE (0.3 microM in 2 microliter saline; pH 6.0-6.5) into the third ventricle of females which had been treated neonatally with two different doses of testosterone propionate (TP; 10 or 100 micrograms) on day 5 of life. This treatment rendered these animals anovulatory as evidenced by polyfollicular ovaries and a persistent vaginal estrus condition which occurred by 100 days of age. Those females which were determined to be anovulatory were ovariectomized 4 weeks prior to the stereotaxic implantation of an intracerebroventricular (ICV) cannula. Ten to twelve days following cannula placement, animals were primed with either estradiol benzoate (EB; 30 micrograms) or EB and progesterone (P; 5 mg). Two days following steroid priming, NE was infused into the third ventricle at 15.00 h and blood samples were taken via an intra-atrial catheter at 15-min intervals for 2 h before and 2 h after administration. In both TP-treated groups, NE caused rapid and significant (p less than 0.01) elevations in plasma luteinizing hormone (LH) concentrations when animals were primed with EB as compared with control females given acid saline infusions (pH 6.0-6.5). Similar responses to NE were seen after additional priming with P at the same time as EB. Follicle-stimulating hormone (FSH) values did not increase following NE or saline infusion to any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090464 TI - Effect of neonatal treatment with the sex-opposite steroid on gonadotropin responsiveness in rats. AB - This study was performed to determine if two sex differences in gonadotropin responses to negative feedback, the acute postcastration rise and the effect of follicular fluid (FF) in the acute castrate, could be reversed by neonatal treatment with sex-opposite steroids. Female rats that received testosterone propionate (TP-females) and male rats that received estradiol benzoate (EB-males) neonatally were studied as adults. EB-males showed an LH response to gonadectomy which was much less than control males, and did not differ from control females, which could suggest the hypothesis that neonatal estrogen 'feminizes' the male response to gonadectomy. However, as the postgonadectomy response in both LH and FSH was depressed in both TP-females and EB-males in comparison to their respective matched sex controls, neonatal steroid treatment appears simply to impair hypothalamic-pituitary function. This is not a result of decreased pituitary responsiveness to GnRH in TP-females and EB-males. On the other hand, neonatal steroid treatment does not change the sex-specific response to imposition of peptide negative feedback (i.e., FF administration). In control and TP-females, FF significantly suppressed serum FSH levels, both in intact animals and 9 h after gonadectomy. In both control and EB-males, FF suppressed FSH in intact animals, but failed to do so in acute castrates. Thus, neonatal steroid treatment does not reverse the sex differences in gonadal-gonadotropin interrelations, but rather causes an impairment in the acute recognition of loss of negative feedback at the hypothalamic level. PMID- 3090465 TI - Continuous infusion of growth hormone-releasing factor: effects on pulsatile growth hormone secretion in normal rats. AB - The effects of a continuous infusion of growth hormone-releasing factor (GRF) on pulsatile growth hormone (GH) secretion were studied in conscious, freely moving rats. Male Sprague-Dawley rats were prepared with 2 indwelling venous catheters and were then housed individually for 6-16 days in isolation chambers. After this period, normal saline, 1.5 microgram/h GRF or 15 micrograms/h GRF were continuously infused for 8 or 31 h via one of the catheters. Blood samples were drawn at approximately 20-min intervals via the other catheter during the last 6 7 h of the infusion. Plasma GH concentrations were determined by RIA. Saline treated animals exhibited the typical pattern of spontaneous GH pulses. The frequency of GH pulses in animals infused with either dose of GRF was not different from that of the saline-infused rats. Likewise, trough GH concentrations were similar in all three treatment groups. However, peak GH concentrations in the rats receiving the 15-micrograms/h GRF infusion were remarkably higher than the concentrations observed in the other two groups, regardless of the duration of the infusion. This resulted in mean GH concentrations being significantly higher (p less than 0.01) in the 15 micrograms/h GRF-infused rats. These results demonstrate that pituitary episodic GH secretion continues even in the presence of a continuous GRF stimulation. PMID- 3090467 TI - Role of arachidonate metabolism on the in vitro release of luteinizing hormone and prolactin from the anterior pituitary gland: possible involvement of lipoxygenase pathway. AB - The aim of the present study was to evaluate whether arachidonic acid metabolism may play a role on luteinizing hormone (LH) and prolactin (PRL) release directly at the pituitary level. To this purpose, exogenous arachidonic acid, alone or in presence of inhibitors of cyclooxygenase (indomethacin:IND) and lipoxygenase pathways (nordihydroguaiaretic acid:NDGA), was added to perfused rat anterior pituitary cells. PGE, PGF alpha, LH and PRL levels present in the eluate were assayed with specific RIA methods. Both PGE and PGF alpha show a dose-related response after the addition of increasing doses of arachidonic acid. The addition of 0.05 mM arachidonic acid induces an increase of LH and PRL. The addition of IND to the perfusion medium highly potentiates the stimulatory effects induced by arachidonic acid on LH and PRL release. On the contrary, the addition to the medium of either NDGA or IND plus NDGA completely reverses the stimulatory action induced by arachidonic acid alone. The present results suggest that: adenohypophyseal cells are able to metabolize exogenous arachidonic acid; arachidonic acid induces an elevation in LH and PRL levels; lipoxygenase pathway metabolite(s) are likely involved in these activities, and the site of action of arachidonic acid is at the pituitary level. PMID- 3090468 TI - Effects of barbiturates on energy metabolism by cultured astrocytes and neurons in the presence of normal and elevated concentrations of potassium. AB - Rates of consumption of oxygen and of the formation of CO2 from [U-14C]glucose were studied in primary cultures of either astrocytes or neurons of the cerebral cortex. An increase of the extracellular concentration of potassium from 5 to 55 mM caused an increase in uptake of oxygen and in the production of CO2 in the astrocytes but not in the neurons. Pentobarbital (0.25-1.0 mM) or phenobarbital (1 mM) abolished the stimulation of oxygen uptake and/or the production of CO2 produced by potassium in the astrocytes with less (CO2 production) or no (oxygen uptake) effect at a normal concentration of potassium. In the neurons, pentobarbital (0.1-1.0 mM) caused, in contrast, a moderate inhibition of the production of CO2 and uptake of oxygen which was at least as pronounced at the small concentration of potassium. These results suggest that the pronounced inhibition of the stimulation of uptake of oxygen induced by potassium in brain slices is exerted on astrocytes, whereas the more modest decrease in uptake of oxygen at a small concentration of potassium is a neuronal phenomenon. PMID- 3090469 TI - Gamma-aminobutyric acid and the high pressure neurological syndrome. AB - Sodium valproate, nipecotic acid, diaminobutyric acid (DABA) and beta-alanine are drugs which enhance transmission mediated by gamma-aminobutyric acid (GABA) by a variety of mechanisms. They were used to study the role of GABA in the high pressure neurological syndrome (HPNS) in the rat. Sodium valproate, nipecotic acid and DABA reduced the increase in slow waves seen in the electroencephalogram (EEG) of control rats at pressures above 10-20 ATA; however, only sodium valproate had a beneficial effect on the behavioural signs of the high pressure neurological syndrome (tremor, myoclonus and convulsions). Sodium valproate is also thought to decrease neurotransmission produced by excitatory amino acids; thus, these results suggest that GABA is not one of the major neurotransmitters involved in all aspects of the high pressure neurological syndrome and that changes in excitatory neurotransmission may affect the behavioural signs. PMID- 3090466 TI - Suppression of progesterone-induced gonadotropin surge by adrenergic agonists in estrogen-primed ovariectomized rats. AB - An involvement of catecholamines in the preovulatory gonadotropin surge has been proposed for many years. Specifically, an alpha-adrenergic mechanism has been implicated in the stimulation of ovulation and LH release. On the other hand, little is known regarding the possible role of adrenergic neurotransmission once a gonadotropin surge has been initiated. In this study, drugs which affect adrenergic receptors were administered centrally to estrogen-primed ovariectomized rats and the effects on serum concentrations of LH and FSH induced by treatment with progesterone at 08:00 h were examined. As expected, the progesterone treatment caused a significant (p less than 0.05) increase in blood LH and FSH levels by 14:00 and 15:00 h, respectively, when compared with those seen at 13:00 h. In control rats that received isotonic saline intraventricularly at 15:00-16:00 h, both LH and FSH levels continued to rise linearly and reached peak levels by 17:00 and 18:00 h. By contrast, intraventricular infusion of norepinephrine at 16:00 h caused a significant decrease (p less than 0.05) in LH levels when compared with the saline-infused control groups. Moreover, rats that received intraventricular infusion of phenylephrine (an alpha 1-adrenergic agonist) at 15:00 h failed to show a significant increase in LH and FSH levels until 19:00 h; this inhibitory effect was mimicked by a relatively more specific alpha 1-adrenergic agonist, methoxamine. Consistent with our previous findings, animals which received intraventricular isoproterenol (a specific beta-adrenergic agonist) at 15:00 h also responded with suppressed serum LH levels at 16:00-19:00 h when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090470 TI - Three uptake systems in synaptosomes for nipecotic acid and beta-alanine. AB - An earlier finding that three systems were responsible for the uptake of gamma aminobutyric acid by synaptosomes was corroborated. In addition, the existence of three uptake systems for RS-nipecotic acid and beta-alanine was demonstrated. We have called these systems high affinity, medium affinity and low affinity uptake systems respectively. In the case of all three substrates, the high affinity system Km values were around 1 microM or less, the medium affinity system Km values were in the range 10-46 microM, and the low affinity system Km values were in the range 290-3400 microM. PMID- 3090471 TI - Isolation and properties of sheep neurohypophysial nerve terminals. AB - Nerve terminals were isolated from sheep posterior pituitary lobes using a collagenase digestion technique. Freshly dispersed terminals, and terminals cultured for up to 3 days were examined by immunofluorescence microscopy. Immunohistochemical results suggested the presence of immunoreactive-neurophysin, -oxytocin and -vasopressin in membrane-bound structures. Membrane depolarization induced by high concentrations of potassium ions stimulated oxytocin release. This release was attenuated in the absence of calcium ions. The calcium ionophore, A23187, was also an effective stimulator of oxytocin secretion. These data suggest that neurohypophysial nerve terminals prepared by a collagenase dispersion procedure may be suitable for the investigation of posterior pituitary secretion mechanisms. PMID- 3090472 TI - Angiotensin II stimulates inositol phosphate formation in rat anterior pituitary glands. AB - The effect of angiotensin II (AII) on polyphosphoinositide (PPI) turnover at the pituitary was studied. When [3H]inositol-prelabelled rat anterior hemipituitaries were incubated with AII (10 microM) for 30 min in the presence of Li+ (10 mM), the production of IP, IP2 and IP3 were increased to 182, 199 and 158% of paired control values. Time course studies showed that the stimulation of IP3 formation by AII was significant after 2 min incubation and preceded the accumulation of the other inositol phosphates. The specificity of the AII effect was confirmed by inhibition with the specific AII antagonist, saralasin. These findings suggest that AII action at the anterior pituitary can be mediated via the early hydrolysis of PPI. PMID- 3090473 TI - Administration of intraspinal morphine sulfate for the treatment of intractable cancer pain. AB - A total of 24 patients with intractable cancer pain were evaluated as candidates for spinal morphine therapy. Temporary trials were carried out with bolus injections of preservative-free morphine sulfate via percutaneously inserted epidural catheters. Fourteen patients felt that pain relief was sufficient to warrant long term morphine application, and permanent drug delivery systems were implanted. These consisted of an Ommaya reservoir and an epidural spinal catheter in 6 patients and an Infusaid pump with either an epidural or subarachnoid spinal catheter in 8 patients. Pain relief with these systems was felt to be excellent in 7 patients, good in 4 patients, and fair in 3 patients. There was a statistically significant reduction in supplemental narcotic use between the pre- and postoperative periods (P less than 0.001). Median survival after operation was 3.0 months (mean, 5.0 months), with a range of 1 to 23 months. Tolerance was seen in all patients regardless of the mode of drug delivery, but it occurred more quickly with bolus injections than with continuous infusion (statistically significant difference, P less than 0.05). A persistent cerebrospinal fluid fistula developed in 1 patient; this required wound revision. No other serious complications or episodes of respiratory depression occurred. We conclude that intraspinal morphine sulfate is a beneficial treatment option for cancer patients in whom pain has become debilitating and unresponsive to oral or parenteral narcotic regimes. PMID- 3090474 TI - Reactivity of the dopa-dopamine-noradrenaline-adrenaline system in epileptic patients. PMID- 3090475 TI - Intrinsic neocortical organization: some comparative aspects. PMID- 3090476 TI - The long-term course of primary generalized epilepsy with persisting absences. AB - The long-term course of primary generalized epilepsy with absences persisting after the age of 30 to 61 years was studied in 26 patients, each followed clinically and by EEG for 20 to 37 years. Whether treated or not, absences became less frequent, but only rarely ceased, and 92% of patients with persisting absences eventually developed generalized convulsions. EEG background activity did not deteriorate, and the classic spike and wave complexes remained typical in 84% of patients. In 36% of cases, almost all of them women, psychomotor slowing was observed, which did not affect job performance. It was not related solely to duration or severity of epilepsy, or to antiepileptic drugs, and some hormonal mechanism may be partly responsible. PMID- 3090478 TI - [Right paraduodenal internal hernia associated with annular pancreas and mucosal diverticulum of the duodenal window. Etiopathogenetic interpretation]. PMID- 3090479 TI - [Home nutritional support]. PMID- 3090477 TI - Immunobiology of brain tumors. AB - The treatment of the cerebral glioma continues to challenge neurosurgeons and basic scientists. The lack of major success with chemotherapy and radiation therapy has spurred further investigation into the biology of this tumor and host reactions to it. Much of this research has centred upon evaluation of tumor cell antigenicity and the cellular immune responses to the glioma. Contrary to previous considerations evidence suggests that astrocytes, glioma cells and tumor endothelial cells may all have pivotal roles in the initiation and prolongation of both local and systemic immune responses to the tumor. In this review we will discuss the immunobiology of the glioma with specific reference to the interactions between the tumor and the host immune system. In addition, ideas for potential therapeutic manipulation of the host-glioma immune interactions will be reviewed stressing potential pitfalls and risks. PMID- 3090480 TI - [Total enteral nutrition. Principles and clinical applications in surgery]. PMID- 3090482 TI - Teaching gerontologic nursing. PMID- 3090481 TI - Intussusception of small bowel secondary to jejunal diverticulosis. PMID- 3090483 TI - The amygdala and male reproductive functions: I. Anatomical and endocrine bases. AB - The present review is mainly concerned with the role of the amygdala (AMY) in male sexual behaviour and presents the characteristics of neuroanatomical and neuroendocrine organization of the cortico-medial amygdala as compared to the medial preoptic area (MPOA), in relation to sexual behaviour and gonadotropin secretion. It stresses the part played by AMY in processing sensory information which afterwards reaches the hypothalamus (HYP). Some data on the different function of steroids and luteinizing hormone releasing hormone (LHRH) systems within AMY and MPOA are provided. The role of AMY in the positive feedback effect on luteinizing hormone (LH) secretion and the involvement of steroid and opiate interaction as its mechanism are suggested. AMY is proposed to integrate external and internal sensory information granting the optimal conditions for sexual performance and possibly for regulation of LH release according to the behavioural context. The steroid content of AMY may influence these processes. PMID- 3090484 TI - The WHO programme of prevention and control of vitamin A deficiency, xerophthalmia and nutritional blindness. AB - The vast extent and the world wide distribution of vitamin A deficiency is discussed. Its epidemiology is reviewed and sources of vitamin A in diets recorded, along with the high requirements of children. Strategy for prevention is described under three headings--short, medium and long term steps. Strategies in many countries received notice. PMID- 3090486 TI - Clinical and bacteriological efficacy of mupirocin (Bactroban): a new topical antibiotic. PMID- 3090485 TI - Changes in levels of dependency and predictors of mortality in elderly people in institutional care in Dunedin. AB - The 1983 study of dependency of subjects in institutional care in Dunedin was repeated two years later. A significant increase in levels of dependency in residential homes, particularly in the Religious and Welfare sector was found. In 1983 there were 29 high dependency residents and 73 medium dependency residents in residential homes. In 1985 these numbers had increased to 55 and 86 respectively. There was no change in the number of low dependency residents. In 1983, 6 high dependency residents had been admitted to residential home care in the year prior to the study. In 1985 the number of high dependency residents recently admitted had increased to 23. There had also been a significant increase in the dependency of patients in Religious and Welfare continuing care hospitals. Of the 933 subjects in institutional care in 1983 who were able to be followed, 354 (37.9%) died in the following 2 years. Mortality rate was higher for those in hospital care (48.1%) than for those in residential home care (29.6%). Mortality rates were higher in more dependent subjects and this was evident for each measure of dependency. PMID- 3090487 TI - The changing emphasis in health expenditures in New York State. PMID- 3090488 TI - The sterility testing of dispensed radiopharmaceuticals. AB - The benefits of retrospective sterility tests on radiopharmaceuticals, were assessed by following the survival of bacteria in non-radioactive and radioactive kits and generator eluate over a period of 5 days. The response of bacteria inoculated into non-radioactive materials ranged through death, survival and growth. The response of bacteria inoculated into radioactive materials was either death or survival. The value of retrospective sterility testing is doubtful and an improved test method is suggested. PMID- 3090489 TI - Ovulation induction with human menopausal gonadotropins. AB - This review has summarized the evolution of hMG stimulation of ovulation in amenorrheic individuals, its monitoring, and its complications. Based on the principles learned from these individuals, use of hMG has now extended to women with cervical mucus deficiencies or luteal phase defects, as well as in vitro fertilization. Recommendations regarding the use of hMG at the current time when assessment by both serum E2 and ultrasound are available have been made. Briefly, it is suggested that an "E2 window" of at least 1000 pg/ml be achieved over the course of a 9- to 12-day follicular phase. Furthermore, assessment of these monitoring modalities should be made in combination in order that findings from one modality alone not be allowed to initiate premature hCG administration. PMID- 3090490 TI - Fetal liver ultrasound measurements in isoimmunized pregnancies. AB - Sixteen isoimmunized pregnancies at risk for erythroblastosis fetalis were managed by serial amniocenteses for bilirubin delta optical density at 450 nm (delta OD450). Before amniocentesis each fetus was evaluated ultrasonically and the fetal liver size, the abdominal circumference, and the umbilical vein diameter, in both the fetal liver and the umbilical cord, were measured. The ultrasonically determined fetal liver size, as well as its growth rate, was found to be greater than normal during the last two weeks before intervention (intrauterine transfusion or delivery) in all eight fetuses with severe hemolytic disease. The umbilical vein diameter in the fetal liver was above normal in only one fetus, whereas the abdominal circumference was increased in only three of the eight severely affected fetuses. These data suggest that serial fetal liver ultrasound measurements may be useful as an adjunct to amniotic fluid analysis to predict the severely affected fetus in need of prompt intervention (intrauterine transfusion or delivery). PMID- 3090491 TI - Blood gases and acid-base status of the human second-trimester fetus. AB - Maternal arterial, umbilical venous, and umbilical arterial blood were obtained at fetoscopy in the second trimester and analyzed for blood gases and acid-base indexes. In comparing umbilical venous (N = 31) with maternal arterial (N = 39) samples, the mean (+/- SD) PO2 was lower (55 +/- 7 versus 100 +/- 15 mmHg, P less than .001) and PCO2 (37 +/- 4 versus 34 +/- 4 mmHg), bicarbonate (20 +/- 2.0 versus 18.5 +/- 1.5 mmol/L), lactate (1.10 +/- 0.25 versus 0.80 +/- 0.30 mmol/L), and base excess (-4.2 +/- 2.3 versus -6.0 +/- 1.5 mmol/L) were higher (P less than .001). The mean umbilical venous pH did not differ significantly from the maternal arterial (7.358 +/- 0.040 versus 7.373 +/- 0.035). Comparing umbilical arterial (N = 21) with umbilical venous (N = 31) samples, the PO2 level was lower (34 +/- 4 versus 55 +/- 7 mmHg, P less than .001) and PCO2 higher (42 +/- 4 verus 37 +/- 4 mmHg, (P less than .001); the pH was marginally lower (7.339 +/- 0.03 versus 7.358 +/- 0.040; P less than .05) and bicarbonate higher (22 +/- 1.5 versus 20 +/- 2.0 mmol/L, P less than .001). Umbilical arterial and umbilical venous values were similar in the case of lactate and base excess. PMID- 3090492 TI - Two-year prospective study in Colombia of Norplant implants. AB - A clinical trial of levonorgestrel-releasing Norplant implants used for contraception was undertaken in two cities in Colombia. Through two years in which 389 women had accumulated 594 years of use, there were no pregnancies. In a comparison group of copper intrauterine device acceptors, the one-year pregnancy rate was 1.1 per 100. Menstrual disturbances associated with progestin-only administration were the principal side-effects, and the major reason for cessation of use. Continuation among users of the implants was at the same or at a higher rate than observed among users of the intrauterine device. Advantages and disadvantages of alternate sites for implant placement are discussed. PMID- 3090493 TI - Pregnancy in women with different types of von Willebrand disease. AB - The course and outcome of pregnancy in women with different types of von Willebrand disease (3 type I, 1 subtype IIA, and 1 subtype IIB) are described. In all patients, factor VIII increased and reached normal levels before delivery, whereas the bleeding time remained prolonged; in subtypes IIA and IIB the abnormal multimeric structure of von Willebrand factor remained unchanged. Deliveries were uneventful in all patients, with two spontaneous vaginal deliveries and three cesarean sections, despite the fact that no replacement therapy was given. Hence, the most important determinant of abnormal hemorrhage during delivery is low factor VIII; the prolonged bleeding time can be compensated for by meticulous surgical hemostasis and efficient contraction of the uterus. Replacement therapy with plasma derivatives can usually be avoided providing that normal factor VIII levels have been attained at delivery. PMID- 3090495 TI - The long-term terminally ill. Who will pay their bills? An overview. PMID- 3090494 TI - Successful therapy of penicillinase-producing Neisseria gonorrhoeae pharyngeal infection during pregnancy. AB - The relative frequency of pharyngeal gonococcal infection may be increased in certain prenatal populations. Therapy of penicillin-sensitive strains of Neisseria gonorrhoeae is associated with acceptable cure rates using aqueous procaine penicillin with probenecid. Infection of the oropharynx of pregnant women with penicillinase-producing strains is more problematic. The antibiotics normally used for the therapy of uncomplicated penicillinase-producing N gonorrhoeae infections, spectinomycin or cefoxitin, are not effective in the therapy of pharyngeal infection. Reported is the first case of penicillinase producing N gonorrhoeae oropharyngeal infection during pregnancy. The patient was successfully treated with trimethoprim/sulfamethoxazole, and no maternal or neonatal morbidity was noted. PMID- 3090497 TI - Assuring continuity of care through a hospital-based home health agency. PMID- 3090496 TI - Relation of vitreous amyloidosis to prealbumin. AB - Amyloid fibrils were isolated from the vitreous of 9 patients with familial amyloidosis. The material of all patients contained proteins reacting in double immunodiffusion with an antiserum against an amyloid protein which previously has been shown to be prealbumin-related. Two out of five tested vitreous amyloid materials also showed a reaction of identity with antihuman prealbumin. It was shown by electrophoresis that the amyloid subunit consisted of two low molecular weight components, one in size similar to prealbumin and one slightly smaller, which appears to be a degradation product of prealbumin. The proportion between the two components seems to vary. It is concluded that besides the presence of an abnormal prealbumin, other factors are of importance for the formation of amyloid precipitates in the vitreous. PMID- 3090499 TI - Joint ventures and home health care. PMID- 3090498 TI - A contractual relationship between a visiting nurse association and a hospice. PMID- 3090500 TI - Risk management and home health care: the time is now. PMID- 3090501 TI - The home care client record project: model forms and comprehensive guidelines. PMID- 3090502 TI - The JCAH home care project. PMID- 3090503 TI - Medicare's prospective payment system for hospitals: the impact on nursing home quality. AB - How are changes in Medicare affecting the quality of long term care? Finding an answer to this question is made difficult by the many variables that must be considered and the lack of concrete data on the subject. The variables include the care requirements of Medicare patients being discharged from hospitals to nursing homes, the availability and accessibility of skilled-care beds, the trends in utilization of skilled-care beds, and the capability of nursing homes to provide the care required by these patients. Anecdotal data suggest that Medicare patients are being discharged from hospitals earlier, sicker, and with more complex skilled nursing requirements than before the implementation of prospective payment, that there has been limited collaboration among hospitals and nursing homes during this period of transition in the Medicare system, and that nursing home administrators and staffs are increasingly concerned about the actual cost of providing care to a sicker group of patients and about the qualifications of staff to meet more complex care needs. One positive outgrowth of this situation is an increase in collaboration among hospitals and nursing homes. Nursing home staff are now more apt to visit a patient in the hospital to perform a preadmission assessment. Such collaboration can help avoid inappropriate nursing home admissions and improve continuity of care for patients who are admitted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090504 TI - The computer in quality control of hemodialysis patient care. AB - A computerized, custom-designed medical information system (MIS) has been used for more than eight years in the care of patients with chronic renal failure treated by hemodialysis in a Cincinnati medical center. A comprehensive clinical data base that forms the core of the system readily serves the need for sophisticated quality control analysis. Application of the MIS in the day-to-day management of patients in one limited care dialysis clinic is detailed, with particular attention to its capacity to contribute to the quality of care of the individual patient. Data can be stored in the system periodically with relative ease; this enables physicians, nurses, and other personnel concerned with patient care to monitor the quality of procedures and treatments used in their patients. The system is shown to be cost-effective. PMID- 3090505 TI - The use of a multidisciplinary committee to manage the risk of suicide in a VA domiciliary. AB - The White City Domiciliary in Virginia created a multidisciplinary committee to provide immediate assessment and management of patients with suicidal and violent behavior. The study concludes that the committee effectively participated in crisis evaluation and intervention and has been accepted as a valuable quality assurance clinical and management tool. PMID- 3090506 TI - Hospital--nursing home collaboration. AB - In the present health care environment, the provision of quality care for the elderly depends on collaboration between hospitals and nursing homes. Nathan Miller Center for Nursing Care, Inc, a skilled nursing facility in White Plains, New York, and Montefiore Medical Center, a tertiary care hospital in Bronx, New York, developed a variety of joint educational programs in geriatrics for their staffs and for the local medical community. These programs not only helped improve patient care directly in such areas as development of care plans but also led to joint projects for research on geriatric care issues. PMID- 3090507 TI - Creative revenue generation and cost containment in a public hospital. PMID- 3090508 TI - In vivo response times for a heated skin surface CO2 electrode during rest and exercise. AB - The continuous, noninvasive estimation of arterial carbon dioxide tension (PaCO2) by heated skin surface electrodes has recently become available for pediatric patients. Skin surface (PsCO2) electrodes can enhance the safety of procedures such as intubation, bronchoscopy, ventilator changes, sleep studies, or measurement of the ventilatory response to CO2 or hypoxia. However, clinical situations that include rapid changes in PaCO2 demand knowledge of the in vivo response time. We compared the response of a heated PsCO2 electrode to end tidal CO2 (PetCO2) during abrupt changes in inspired CO2 from room air to 7% CO2 and back to room air. We obtained 54 curves on nine healthy subjects. There was an initial lag time with less than a 10% change in PsCO2. Then PsCO2 approached PetCO2 exponentially. For subjects at rest changing from breathing room air to 7% CO2, the initial lag time was 40 +/- 2 seconds and the 50% response time of the exponential portion was 46 +/- 3 seconds. Thus, it took 86 seconds for the electrode to record a 60% response to an abrupt increase in inspired CO2. The initial lag and 50% response time were considerably shorter during exercise (30 +/- 2 and 33 +/- 2 seconds) and even shorter when switched from breathing 7% CO2 to room air (23 +/- 2 and 21 +/- 2 seconds). Exercise did not further reduce the response time when CO2 was initially elevated, suggesting the faster response time was due to vasodilation of the skin due to elevated CO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090509 TI - Effect of nutritional rehabilitation on the development of intestinal brush border disaccharidases of postnatally malnourished weanling rats. AB - The reversibility of the effects of postnatal malnutrition on the intestinal brush border enzymes and somatic and intestinal weights were examined using either ad libitum or restricted feedings. Malnutrition was induced in the immediate postnatal period by expanding newborn rat litters to 20 pups/dam. At 21 days of age, malnourished pups exhibited significantly decreased body and intestinal weights as compared to those from control litters. Malnourished pups also had significantly elevated lactase specific activities whereas sucrase and maltase activities were not affected in the proximal small intestine. With subsequent nutritional rehabilitation by an ad libitum (food available 24 h/day) or restricted feeding regimen (food available 2 h/day), body and intestinal weights remained significantly depressed by 56 days in malnourished as compared to control animals. Rats on 2-h feedings consumed approximately 35% of the food consumed by their ad libitum-fed counterparts. Comparison of the ratio of weight gained to the amount of food consumed did not demonstrate a greater food efficiency with any particular feeding pattern. With ad libitum or restricted feedings, lactase specific activity in the proximal segment attained control values by 14 days. Restricted feedings resulted in an apparent elevation of specific activity of sucrase and of maltase, when rats were sacrificed at one chosen time point. Multiple time studies in a 24-h cycle showed that maximal elevations in enzyme activities were associated with feeding time. There were no significant differences in mean specific daily enzyme activities between the two feeding regimens. Restricted feedings show no advantage in enzyme efficiency or in promoting the rate of recovery of the intestine after postnatal malnutrition. PMID- 3090510 TI - Serum apolipoproteins A-I and B in 2,854 children from a biracial community: Bogalusa Heart Study. AB - Serum apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B) profiles were examined in 2,854 children, 5 to 17 years of age, from a total biracial community. Black boys had higher apo A-I levels than white boys (P less than .001), whereas girls showed no such race-related difference. Black-white difference in apo A-I persisted among boys with similar triglyceride levels provided that triglyceride levels were high. The ratio of high-density lipoprotein cholesterol (HDL-C)/apo A-I was higher in black than in white children, irrespective of sex (P less than .001). Only black children showed sex related differences for apo A-I (boys greater than girls, P less than .05). Sex related differences were seen in white children for HDL-C/apo A-I ratio (boys greater than girls, P less than .001) and in children of both races for apoB (girls greater than boys, P less than .01). Age-related changes were more apparent for apo A-I and HDL-C/apo A-I ratio than for apo B. A progressive decrease in apo A-I was noted during sexual maturation only in white boys. The magnitude of inverse association of apo B to HDL-C was less strong in black children (P less than .01). Although apo A-I was inversely correlated with very low-density lipoprotein cholesterol and triglycerides in white children, no association was noted in black children. These findings are indicative of intrinsic metabolic differences among the race-sex groups, resulting in variability in lipoprotein composition and levels and atherogenic potential. PMID- 3090511 TI - Prospective evaluation of percutaneous central venous silastic catheters in newborn infants with birth weights of 510 to 3,920 grams. AB - With improved neonatal survival, especially of very low birth weight infants, our efforts should be directed toward reduction of morbidity. Sick preterm infants require total parenteral nutrition for prolonged periods of time due to extreme prematurity and feeding intolerance. However, the use of surgically placed Broviac catheters has been associated with a high complication rate. A prospective study of 53 percutaneous central venous Silastic catheterizations for administration of total parenteral nutrition was performed in 45 newborn infants. At the time of catheter insertion, 37 babies weighted less than 1,500 g and 19 weighed less than 1,000 g. Percutaneous central venous catheters were placed successfully the first time in 50 of 55 attempts. In three babies, insertion was successful on second attempt. The catheters remained in place for 25.4 +/- 16.7 days ([mean +/- SD] range two to 80 days). In babies weighing less than 1,000 g, the catheters remained in place for a longer period of time (34.0 +/- 18.0; range 12 to 80 days). Sixty-six percent of the catheters were removed electively. There were four cases of bacteremia (7.5%), and the overall incidence of mechanical complications was 26.4%. We conclude that percutaneous central venous catheters can be used safely and effectively in newborn infants for prolonged administration of total parenteral nutrition, especially in neonates weighing less than 1,000 g. PMID- 3090512 TI - Fecal alpha 1-antitrypsin and hemoglobin excretion in healthy human milk-, formula-, or cow's milk-fed infants. AB - There is concern that whole cow's milk feedings may be associated with intestinal abnormalities in infants. We studied this issue by measuring random fecal samples for alpha 1-antitrypsin (FA1AT) and hemoglobin (FH) concentrations in 820 healthy infants up to 12 months of age. Subjects were fed either human milk, formula, or fresh whole cow's milk. Solid foods were given ad libitum. Fecal samples were also tested for occult blood with Hematest reagent tablets. None of the infants younger than 6 months of age were receiving fresh whole cow's milk. We found small but statistically significant differences in mean FA1AT between the three feeding groups (P less than .0001): human milk (n = 354) greater than formula (n = 320) greater than cow's milk (n = 146). The younger subjects fed either formula or human milk tended to have higher FA1AT concentrations than did the age-matched subjects who were not consuming solid foods (P less than or equal to .005). Daily FA1AT excretion, FA1AT concentration, and daily stool output were subsequently determined on a separate group of 40 infants 8 to 12 months of age to ascertain whether differences in total daily FA1AT excretion occur in children fed different types of milk. Total daily FA1AT excretion was similar in the three milk feeding groups. An inverse correlation between FA1AT concentration and daily stool output was also found (P less than .001). The overall rate of detectable FH in 792 stool smears was 2.1% and unrelated to type of milk feeding. Of 705 stool smears, 3.5% had positive Hematest reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090513 TI - Biochemical, clinical, epidemiologic, genetic, and pathologic data in the pediatric age group relevant to the cholesterol hypothesis. PMID- 3090514 TI - [A method of early diagnosis of hemolytic disease of the newborn]. PMID- 3090515 TI - Effects of carbon dioxide inhalation on preoptic thermosensitive neurons. AB - The effects of inspired CO2 on preoptic thermosensitive neurons were studied in urethanized rats. Most of the neurons changed their activities diversely while the rat breathed 4%, 7%, and 10% CO2 gas mixtures. Half of the neurons increased activity during CO2 inhalation, but activity was not necessarily intensified by elevating CO2 concentration. Thermosensitive neurons tended to increase activity more than thermally insensitive neurons. The effect of CO2 on sensitivity of thermosensitive neurons was also examined by regression of neuronal activity on preoptic temperature. The slopes of the regression lines during CO2 inhalation did not differ significantly from those during air inhalation in either warm sensitive or cold-sensitive neurons, but CO2 did elevate the intercepts in most instances (P less than 0.01). However, if P less than 0.05 is accepted as a significance level, the slopes of the regression lines for warm-sensitive neurons tended to decrease during CO2 inhalation (9/39 pairs). The present results indicate that preoptic thermosensitive neurons generally increase their activities and modify their thermosensitivities during CO2 inhalation. PMID- 3090516 TI - Hemophilic patients with an inhibitor to factor VIII treated with high dose factor VIII concentrate. Results of a collaborative study for the evaluation of factor VIII inhibitor titer, recovery and half life of infused factor VIII. AB - The long term treatment of hemophilic patients with an inhibitor to Factor VIII has been difficult although some success with immunosuppressive agents has been reported. Eighteen hemophilic patients, mainly from Bonn in Germany, but also from other countries, have completed a high dose Factor VIII treatment in an attempt to reduce their inhibitor titer and induce "immune tolerance" to Factor VIII. Plasma samples from the 18 patients collected before and after infusion of 50 units Factor VIII/kg body weight were sent to five laboratories to evaluate inhibitor titer, Factor VIII recovery and half life. This collaborative study demonstrated a close correlation from one laboratory to another concerning inhibitor titration and Factor VIII recovery. The conclusion of the study is that all patients treated with this protocol showed an undetectable or low inhibitor titer against Factor VIII indicating that they can be efficiently treated with Factor VIII. PMID- 3090518 TI - Nucleotide sequence of a Drosophila melanogaster H1 histone gene. PMID- 3090517 TI - Transcriptional and posttranscriptional control of immunoglobulin mRNA production during B lymphocyte development. AB - A variety of cell lines representing different maturation stages of the B lymphocyte were used to analyse developmental changes in the transcriptional pattern through the mu-delta locus and the relationship between mu mRNA accumulation and transcriptional activity. As anticipated from earlier studies, we observed that RNA polymerase loading in the region between the mu m cleavage/poly A addition site and the delta 1 exon is markedly decreased in IgM secreting cells compared to cells bearing surface IgM or surface IgM and IgD. In several IgM secreting hybridomas, transcriptional termination mainly occurred downstream of the first mu m exon. Thus, the predominance of mu s-terminated transcripts in these cells would appear to be principally determined by RNA processing events, most likely by more efficient cleavage at the mu s poly A site and/or less efficient splicing of the C mu and mu m exons. In two plasmacytoma lines, polymerase unloading between the mu s and mu m sites also contributed significantly to the high mu s mRNA phenotype. Our results further indicate that posttranscriptional regulation is largely responsible for the greatly increased accumulation of mu mRNA in the IgM secretors. Interestingly, the sterile-mu RNA components do not seem to be subject to this posttranscriptional regulation. PMID- 3090519 TI - First impressions. PMID- 3090520 TI - Total parenteral nutrition at home. PMID- 3090521 TI - [Primary drug resistance to antitubercular drugs in patients with pulmonary tuberculosis in the years 1978-1982]. PMID- 3090522 TI - Systemic absorption of 14C-glutaraldehyde from glutaraldehyde-treated pulpotomy sites. PMID- 3090524 TI - Effects of methylnitrosourea on visualization of acridine orange binding to DNA in mouse lymphoma L-1210 cells. AB - The purpose of this study is to examine effects of methylnitrosourea (MNU) on electron microscopic visualization of acridine orange (AO) binding to DNA in mouse lymphoma L-1210 cells and to demonstrate alteration of the euchromatin/heterochromatin ratio by morphometry. [3H] uridine uptake into RNA molecule is inhibited and percentage of AO positive cells is decreased to approximately 20% of that of the untreated control cells by treatment of the lymphoma cells with MNU. When the MNU-treated cells are cultured in the presence of 3-amino-benzamide, a specific inhibitor of poly(ADP-ribose) synthetase, the depression in RNA synthesis is prevented, and percentage of AO positive cells as well as numbers of AO chromatin interaction products per single cell nucleus are also completely recovered as compared to those in the untreated cells. In the MNU treated cells the decreased number of AO positive cells coincides with a reduced [3H] uridine uptake as well as with a lowered euchromatin/heterochromatin ratio. The results suggest that visualization of AO chromatin interaction products in the proliferating cells is related not only to RNA synthesis in the cells, but also to the euchromatin/heterochromatin ratio. PMID- 3090526 TI - [Work planning]. PMID- 3090525 TI - Danazol treatment of advanced prostate cancer: clinical and hormonal effects. AB - Danazol was administered to 19 patients with advanced prostate cancer. These patients were treated for periods ranging from 3 days to 18 weeks. There were no objective remissions, but three patients (15.8%) had objectively stable disease (N.P.C.P. criteria) with complete pain control for periods ranging 15-18 weeks. Seven patients experienced tumor flare reactions, one requiring withdrawal of treatment and one resulting in rapid clinical deterioration and death. Four other patients died within 3 weeks and, although they were already in the terminal phase of disease when treatment commenced, it is possible that the deaths were treatment related. This study indicates that danazol has only limited activity in the treatment of advanced prostate cancer and is associated with a high incidence of tumor flare reactions with the risk of rapid clinical deterioration. PMID- 3090527 TI - [Chairside organization: assistance technics]. PMID- 3090528 TI - [Class II malocclusion and bottle feeding]. PMID- 3090523 TI - Central respiratory stimulation produced by thyrotropin-releasing hormone in the cat. AB - Thyrotropin-releasing hormone (TRH) was administered intracerebroventricularly and it's effects on respiration were evaluated in the alpha-chloralose anesthetized cat. Respiratory activity was measured using a Fleisch pneumotachograph to monitor tracheal airflow. TRH (0.28-28 nmol) caused an elevation in respiratory minute volume which was due to an increase in respiratory rate with no effect on tidal volume. The site of TRH-induced tachypnea was in the hindbrain as both injections into the cisterna magna and the fourth ventricle produced similar effects. No changes in respiratory activity were seen when TRH injection was restricted to the lateral and third ventricles (forebrain). Furthermore, systemic administration of TRH (28 nmol) produced no significant respiratory effects. The active analogue, [3-Me-His2]-TRH (2.7 nmol) produced the same respiratory effects as TRH. The inactive analogue, TRH free acid (28-280 nmol), caused no significant change in respiratory activity. The data suggest that TRH interacts with a specific receptor in the hindbrain of the cat to affect respiration. PMID- 3090530 TI - [Plaque control in the interdental spaces: flossing]. PMID- 3090529 TI - [Motivation in oral hygiene: psychological aspects]. PMID- 3090532 TI - [Essential varicosities of the lower extremities]. PMID- 3090531 TI - [Control of work flow: appointments]. PMID- 3090533 TI - [Why a note on healthy nutrition]. PMID- 3090534 TI - [Preventive dental methodology]. PMID- 3090535 TI - Bread mold infection in diabetes. The life-threatening condition of rhinocerebral zygomycosis. AB - Rhinocerebral zygomycosis is a rare but dangerous fungal infection that affects primarily diabetic patients in ketoacidosis but other debilitated patients as well. A high index of suspicion among primary care physicians will lead to earlier diagnosis and help reduce the severe morbidity and mortality associated with the condition. Zygomycosis should be strongly suspected in diabetic patients presenting with unilateral headache, nasal congestion, or facial pain and swelling. If hyphae are not seen in nasal secretions on microscopy, biopsy of infected tissue must be done immediately to establish a diagnosis. Prompt treatment, including appropriate surgical intervention, amphotericin B therapy, and correction of metabolic derangements, is essential. PMID- 3090536 TI - Effect of an elevated level of carbon dioxide containing atmosphere on the growth of spoilage and pathogenic bacteria at 2, 7, and 13 C. AB - The effect of 80% CO2 (balance air) on the survival and growth of microorganisms most often associated with spoilage and foodborne disease in poultry carcasses was compared to air at 2, 7, and 13 C. The CO2 atmosphere substantially retarded the growth of the total bacterial load in uninoculated ground chicken meat and parts at all temperatures when compared to air; however, temperature had a larger overall effect than atmosphere. Ground chicken meat and synthetic broth were inoculated (greater than 10(4) cells/ml or g) with Pseudomonas fragi, Salmonella typhimurium, Staphylococcus aureus, or Clostridium sporogenes and the influence of 80% CO2 and incubation temperature studied. With the exception of Cl. sporogenes, 80% CO2 was inhibitory when compared to air at any given temperature. In most cases, CO2 was more inhibitory at 2 C than at 7 or 13 C. The Cl. sporogenes inoculum failed to grow above initial inoculum levels in any combination of temperature and atmosphere, but samples packed in 80% CO2 had higher numbers of colony forming units than air-packaged samples. This study does not indicate that modified atmosphere packaging of refrigerated poultry in elevated CO2 atmospheres increases the microbial hazards when compared to air at the same temperature. PMID- 3090538 TI - Cancer vaccine goes on trial. PMID- 3090537 TI - The effect of adding essential amino acids and vitamins to the rations of broilers. AB - Four experiments were carried out to investigate the amino acid and vitamin requirements of broilers. The performance of birds fed on control diets formulated according to the recommendations of the National Research Council (1977) was compared to that of birds fed on experimental diets containing additional amounts of essential amino acids (L-lysine and DL-methionine) and vitamins. The control diets varied in protein and metabolizable energy content; the experimental diets were obtained by adding varying additional amounts (10 to 50%) of one or both amino acids and vitamins to the control diets. The experimental diets resulted in consistently better body weight gains than the control diets. The results showed that under the conditions of these experiments, the levels of amino acids and vitamins in the control diets were not optimal for the proper growth and development of broilers and must be increased. PMID- 3090539 TI - Synthesis and efficient isolation procedure for gamma-linked fluorescein methotrexate. AB - Fluorescein isothiocyanate was reacted in dimethyl sulfoxide with a ten-fold excess of diaminopentane, and the mono-substituted thiourea product was isolated by DEAE-cellulose chromatography, lyophilization and acid precipitation from aqueous base. The dried product was then condensed in dry dimethyl sulfoxide with Methotrexate (MTX) activated by prior incubation (30 min) with 1-ethyl-3-(3' dimethylaminopropyl) carbodiimide hydrochloride, and the reaction products were purified by column chromatography on DEAE-cellulose. Exhaustive elution with 1 M ammonium bicarbonate removed several by-products then finally afforded the exclusively gamma-linked fluorescein--MTX derivative. After lyophilization and acid-base precipitation the compound was obtained in good yield (greater than 40%), was homogeneous by reverse-phase HPLC epsilon 493 (0.1 N NaOH) = 66,000 and was a comparable inhibitor to MTX for rat-liver dihydrofolate reductase. PMID- 3090541 TI - [Lactotropic and thyrotropic functions of the hypophysis in polycystic ovary syndrome]. AB - An increase in the prolactin basal level was detected in 8 out of 50 patients with ovarian polycystosis. A test with TRH and a simultaneous determination of the levels of prolactin, TTH, T3, T4 were used in 25 patients, of them a hyperergic reaction of prolactin to TRH was detected in 5. A correlation analysis of function of the thyroid was performed. Positive correlation between the levels of prolactin and TTH in patients with hyperprolactinemia and between a maximum increment in percentage to the initial level of TTH and prolactin in patients with a hyperergic reaction of prolactin to TRH was revealed. A conclusion was made of the common nature of disorder in the mechanisms of regulation of prolactin and thyroid function in patients with ovarian polycystosis. PMID- 3090540 TI - [Interrelation between the thyroid and calcium-regulating hormones in patients with hypothyroidism]. AB - The paper is concerned with a comparative analysis of the clinical signs of hypothyrosis, thyroid and calcium regulating functions. A decreased or increased reaction of TTH to TRH was revealed; it was accompanied by disorder of calcium regulating function determined by the level of calcitonin, parathyrin and ionized calcium, all these indices being evaluated by a mathematical table proposed by K. I. Myshkin with relation to a severity of the signs of hypothyrosis. An elevated level of calcitonin in the blood was observed in primary hypothyrosis with an increased reaction of TTH to TRH. A percentage ratio of calcitonin to parathyrin grew with an increased level of ionized calcium. Clinical signs of hypothyrosis either decreased or disappeared completely, clinical signs of hypoparathyrosis (relative hypoparathyrosis) appeared making the diagnosis of hypothyrosis difficult. There was a decrease in the calcitonin content in primary hypothyrosis with insufficient reaction of TTH to TRH. A decrease in the percentage ratio of calcitonin to parathyrin was noted in the normal level of ionized calcium. Clinical signs of hypothyrosis in this case were noticeable. In hypophysial hypothyrosis (pangiopopituitarism) there was a decrease in the levels of calcitonin and parathyrin but their percentage ratio remained normal in a decreased level of ionized calcium. PMID- 3090542 TI - Design and biological activity of analogs of growth hormone releasing factor with potential amphiphilic helical carboxyl termini. AB - A 29-amino acid analog of growth hormone releasing factor (GHRF) was designed in which the sequence of the first six amino acids at the amino terminus was maintained while the postulated amphiphilic helical structure in the remainder of the molecule was optimized. The amino acid sequence of the analog differed from that of the first 29 residues of human GHRF by 13 residues. The peptide was synthesized by the solid-phase procedure in amide and free acid forms, both of which were tested for biological activity. When assayed for the ability to stimulate growth hormone secretion in primary cultures of rat anterior pituitary cells, the amide analog was 1.57 times as potent as GHRF-(1-40)-OH, which was used as the standard for comparison, while the free acid form was 1/6th as potent in the same assay. The two forms of the analog were also tested for stimulation of cAMP formation; they exhibited relative potencies similar to those observed for growth hormone secretion. The high activity of the analog provides good evidence for the importance of an amphiphilic helical structure in the carboxyl terminal portion of the GHRF molecule. PMID- 3090543 TI - Exchange of guanine nucleotide between GTP-binding proteins that regulate neuronal adenylate cyclase. AB - GTP-binding proteins have been demonstrated to stimulate and inhibit rat brain adenylate cyclase without the prior addition of hormone. Exposure of rat cerebral cortex membranes to hydrolysis-resistant GTP analogs results in inhibition (or stimulation) of adenylate cyclase, which persists subsequent to buffer washing. The hydrolysis-resistant GTP photoaffinity probe P3-(4-azidoanilido)-P1-5' GTP (AAGTP) can promote a similar persistent inhibition of adenylate cyclase, and, after removal of unbound AAGTP and subsequent UV photolysis, AAGTP is covalently linked to the 40-kDa inhibitory GTP binding protein, GNi (inhibitory guanine nucleotide binding regulatory subunit of adenylate cyclase). Under conditions where the persistent inhibition of adenylate cyclase is overcome by subsequent incubation with 5'-guanylyl imidodiphosphate or NaF, AAGTP bound to the 40-kDa GNi protein is diminished while that bound to the 42-kDa stimulatory GTP-binding protein (GNs) is increased. Additionally, we have identified a 32-kDa protein that binds AAGTP with an affinity similar to that of GNs. This protein does not appear to be a byproduct of proteolysis as demonstrated by Staphylococcus aureus V8 protease digestion experiments, and it is not a substrate for ADP-ribosylation by bacterial toxins. The sum of the AAGTP bound by the GNi and GNs proteins is constant, and the transfer of nonphotoactivated AAGTP to GNs from GNi is stable to buffer washing. Furthermore, this alteration in the AAGTP-labeling pattern corresponds to the shift in adenylate cyclase from inhibition to stimulation. These data raise the possibility that hydrolysis-resistant GTP analogs might be exchanged directly between the GNi and GNs and that there exists some interaction between those proteins in the regulation of adenylate cyclase activity. PMID- 3090544 TI - Hydroxyl radical "footprinting": high-resolution information about DNA-protein contacts and application to lambda repressor and Cro protein. AB - A method has been developed for making "footprints" of proteins bound to DNA. The hydroxyl radical, generated by reduction of hydrogen peroxide by iron(II), is the reagent used to cut the DNA. Hydroxyl radical breaks the backbone of DNA with almost no sequence dependence, so all backbone positions may be monitored for contact with protein. In addition to defining the DNA sequence in contact with the protein, hydroxyl radical footprints embody structural information about the DNA-protein complex. For example, hydroxyl radical footprints of the bacteriophage lambda repressor and Cro protein show directly that these proteins are bound to only one side of the DNA helix. Additional contacts of lambda repressor and Cro protein with DNA, not observed by other chemical footprinting methods, are revealed by hydroxyl radical footprinting. PMID- 3090545 TI - T-cell and mast cell lines respond to B-cell stimulatory factor 1. AB - The murine lymphokine B-cell stimulatory factor 1 (BSF-1) has been described previously in terms of its action on B lymphocytes. We now provide evidence that BSF-1 is also responsible for two additional biological activities. The first of these is the stimulation or maintenance of a state of activation in mouse T-cell lines. The second activity is the increase in the proliferative rate of certain mast cell lines costimulated with interleukin 3. The T-cell and mast cell activities are mediated by purified BSF-1 and copurify with BSF-1 from supernatants of certain T-cell lines. Each of these activities is inhibited by monoclonal anti-BSF-1 but not by monoclonal anti-interleukin 2 antibody. The antibody inhibition results also indicate that BSF-1 is the major or only source of these two activities in the activated T-cell supernatants that we have tested. PMID- 3090546 TI - Identification of the probable site of choleragen-catalyzed ADP-ribosylation in a Go alpha-like protein based on cDNA sequence. AB - Go alpha, a 39-kDa guanyl nucleotide-binding protein, is functionally and structurally similar to the alpha subunits of the stimulatory and inhibitory guanyl nucleotide-binding proteins (Gs alpha, Gi alpha) of adenylate cyclase and to the alpha subunit of transducin (T alpha), the guanyl nucleotide-binding protein of the retinal photon reception system. A cDNA clone was isolated from a bovine retinal lambda gt10 library by using oligonucleotide probes complementary to sequences in two putative T alpha clones. Partial sequence analysis revealed a deduced amino acid sequence identical to sequences of four tryptic peptides from bovine brain Go alpha. Gs alpha and T alpha are known to serve as substrates for ADP-ribosylation by choleragen. Other workers have established the sequence of the tetrapeptide in T alpha containing the arginine that is ADP-ribosylated and its location in the amino acid sequence deduced from T alpha cDNA. The Go alpha cDNA described here includes a region encoding an amino acid sequence very similar to that surrounding the ADP-ribosylation site in T alpha, consistent with observations that Go alpha can also be a substrate for choleragen. A corresponding sequence in the recently identified Gs alpha cDNA is less homologous to that in T alpha or Go alpha. The reported differences in conditions that promote choleragen-catalyzed ADP-ribosylation of Gs alpha vs. Go alpha could be related to differences in amino acid sequence in the region of the acceptor arginine. PMID- 3090547 TI - RNA splicing and intron turnover are greatly diminished by a mutant yeast branch point. AB - Two mutant genes, both of which contain an A----C transversion at the absolutely conserved branch point of the yeast "TACTAAC box" (TACTAAC----TACTACC), were constructed and introduced into yeast cells. Splicing and gene expression are almost completely eliminated by this mutation, but a low level (approximately equal to 0.1%) of proper splicing is detectable. Branch point mapping indicates that the mutant branch is formed at the normal location--i.e., to cytidine rather than adenosine. The mutant branch is also a very poor substrate for the HeLa cell debranching enzyme. Although splicing of the mutant transcripts is very poor, the cells contain a high level of mutant intron because these excised introns are remarkably stable. The results imply that the normal branch point is important not only for branch formation and splicing but also for intron turnover. PMID- 3090548 TI - The major histocompatibility complex class I heavy chain as a structural subunit of the human cell membrane insulin receptor: implications for the range of biological functions of histocompatibility antigens. AB - Monoclonal antibodies against some of the monomorphic determinants of major histocompatibility complex (MHC) class I molecules reduce insulin binding and precipitate 125I-labeled insulin receptor preparations. A monoclonal antibody with specificity for the insulin binding site on the cell membrane insulin receptor of human cells was used to precipitate insulin receptors from human cell lines and resulted in distinct bands of Mr approximately 130,000, 90,000, and 45,000. The Mr 45,000 molecules thus precipitated were subjected to NaDodSO4/PAGE, eluted from the gels, and found to react with monoclonal antibodies against monomorphic and a polymorphic MHC class I determinant known to be expressed on the cell line used as receptor source. Moreover, a murine thymoma line (RI) with MHC class I expression bound significant amounts of insulin, whereas a MHC class I-negative variant had low insulin binding capacity. Reduction in the density on human cells of the MHC class I heavy chain was obtained by capping with antibodies to beta 2-microglobulin or to the MHC class I heavy chain and resulted in decreased insulin binding, whereas down-regulation of insulin receptors induced increased density of MHC class I molecules. It is concluded that the MHC class I heavy chain and the tetrameric insulin receptor are structurally associated in the cell membrane and suggested that this association may occur by displacement of beta 2-microglobulin by the insulin receptor. PMID- 3090549 TI - Clonal expansion of T cells: a cytotoxic T-cell response in vivo that involves precursor cell proliferation. AB - The response of peritoneal exudate lymphocytes to allogeneic tumor cells was used to determine whether the in vivo generation of cytotoxic T cells (CTL) involved the proliferation of precursor cells. Ten days post-injection, both cytotoxic activity and the formation of conjugates between lymphocytes and target cells were shown to be specific for the immunizing tumor alloantigens and to be effected by Ly-2+ cells. A cell-sorting-based procedure was developed to isolate specific conjugates between red-fluorescence-tagged CTL and blue-fluorescence tagged tumor target cells. When [3H]thymidine was administered during the response, almost all isolated conjugate-forming CTL were 3H-labeled on autoradiography. Thus, the CTL were clearly products of dividing cells, a result that contradicts published data. Reassessment of a previously studied system, which suggested that CTL were not products of cell division, indicated that in that system many of the conjugate-forming cytotoxic cells studied were Ly-2- and nonspecific, and thus perhaps not T cells. We conclude that the clonal selection model is applicable to at least one in vivo T-cell response. PMID- 3090550 TI - Modulation of interleukin 2 receptor expression on normal human lymphocytes by thymic hormones. AB - The expression of interleukin 2 receptors (IL-2R) is a critical step leading to normal lymphocyte proliferation. Since thymosin fraction 5 (TF5), a thymic hormone preparation, enhances lymphoproliferative responses of human cells, we examined the effects of TF5 on the expression of IL-2R on mitogen-stimulated human lymphocytes. TF5 significantly increased the percentage and antigen density of cells expressing IL-2R after stimulation with an optimal concentration of phytohemagglutinin (PHA) when the cells from the same donor exhibited suboptimal responses to PHA alone. The same effect was observed with a suboptimal PHA concentration and with OKT3 monoclonal antibody stimulation. Thymosin alpha 1, a synthetic polypeptide originally isolated in its native form from TF5, was also able to increase IL-2R expression in response to PHA, suggesting that it is the active species in TF5. The enhancement of IL-2R expression was paralleled by increased proliferative responses. Increased IL-2R expression appears to be the direct effect of thymic hormones, since abrogation of interleukin 2 production by cyclosporin A did not affect TF5-mediated enhancement of PHA-induced IL-2R expression. These results point to a physiological role of thymic hormones in the maintenance of normal levels of IL-2R expression. This immunoregulatory activity of thymic hormones might be relevant in the treatment of conditions where there is decreased IL-2R expression, such as the acquired immune-deficiency syndrome, or in the restoration of normal IL-2R expression to lymphocytes from aged individuals. PMID- 3090551 TI - Characterization of major peptides in Creutzfeldt-Jakob disease and scrapie. AB - In Creutzfeldt-Jakob disease three major peptides cosediment with the infectious agent. These distinct peptides are not present in identical fractions from uninfected brain, and bind to polyclonal antibodies raised against "prion protein" purified by protease treatment. Three similar distinct peptides are also found in scrapie-infected brain fractions purified without the use of proteases. To clarify the relationships between these distinct peptides and prion protein, peptides were analyzed on immunoblots after cleavage with various glycosidases. There are two different 34-kDa peptides. One binds to ricin and cannot be detected by nonequilibrium pH gradient electrophoresis, presumably due to its highly acidic or basic pI. A second basic 34-kDa glycopeptide (Gp34) contains multiple terminal sialic acid residues responsible for charge heterogeneity (pI values, 7.2-7.8) and is reduced to a single spot with a pI value of 7.8 after neuraminidase treatment. After (but not before) neuraminidase treatment, secondary D-galactose-like sugars are detectable on Gp34, and a small number of N acetylglucosamine residues probably represent the third sugar residue in an N linked chain. When virtually all sugar residues are removed with endoglycosidase H the molecular weight of Gp34 is reduced by only approximately equal to 2 kDa. The residual peptide strongly binds antibody. A third acidic 24- to 26-kDa species (p26) also binds polyclonal antibodies but, in contrast to Gp34, was unaffected by any glycosidase treatment. Protease-treated peptides showed a very broad array of pI spots, consistent with a heterogeneous protein origin. None of the nonproteolyzed peptides show a clear relationship to prion protein. The number of sugar residues on Gp34 is not consistent with those estimated for prion protein. Although p26 could be the source of the "prion sequence," p26 does not appear to be glycosylated. Regardless, it is likely that all the major peptides described thus far are accumulated or modified normal gene products and are not integral components of the infectious agent. PMID- 3090552 TI - Calcium and calmodulin-enhanced in vitro phosphorylation of hen brain cold-stable microtubules and spinal cord neurofilament triplet proteins after a single oral dose of tri-o-cresyl phosphate. AB - The effect of a single 750-mg/kg oral dose of tri-o-cresyl phosphate (TOCP) on the endogenous phosphorylation of brain microtubule preparations and spinal cord neurofilaments was assessed in hens after the development of delayed neurotoxicity. Protein phosphorylation with [gamma-32P]ATP was analyzed by one dimensional and two-dimensional gel electrophoresis, autoradiography, and microdensitometry. TOCP treatment enhanced the Ca2+- and calmodulin-dependent phosphorylation of tubulin in crude chicken brain cytosol (160% for alpha-tubulin and 140% for beta-tubulin) and cold-stable microtubules (165% and 155% for alpha- and beta-tubulin, respectively). Microtubule-associated protein 2 (MAP-2) phosphorylation was also increased in brain fractions studied--i.e., brain cytosol (145%), cold-stable microtubules (133%), and cold-labile microtubules (328%). There was significant increase in phosphorylation of a 70-kDa protein in the brain cytosol and in the cold-stable microtubule fractions. TOCP also stimulated the phosphorylation of spinal cord proteins of 70 kDa (119%) and 160 kDa (129%) in a Mg2+-dependent manner. Addition of Ca2+ and calmodulin further enhanced the phosphorylation of these 70-kDa (563%) and 160-kDa (221%) proteins as well as of 52-, 59-, and 210-kDa proteins by as much as 126%, 160%, and 196%, respectively. Two-dimensional electrophoresis was carried out to identify these proteins. They were confirmed as alpha- and beta-tubulin (52 and 59 kDa) in brain and spinal cord preparations and the neurofilament triplet proteins (70, 160, and 210 kDa) in the spinal cord preparation. The 70-kDa protein in brain was not neurofilament in origin. Peptide mapping using Staphylococcus aureus V8 protease showed the brain and spinal cord cytoskeletal proteins have identical phosphopeptide patterns in control and TOCP-treated hens, indicating that it was unlikely that the phosphorylation sites were altered by TOCP treatment. PMID- 3090553 TI - Aggressive behavior induces release of nerve growth factor from mouse salivary gland into the bloodstream. AB - Intraspecific fighting induced by 6-8 weeks of social isolation results in massive release of nerve growth factor (NGF) into the bloodstream of adult male mice. The amount of circulating NGF is highly correlated with the number of fighting episodes. Biological, radioimmunological, immunohistochemical, and ultrastructural studies show that NGF is discharged from the salivary gland into the blood within minutes after fighting and reaches the highest level 3-4 hr later. Adrenergic innervation of the salivary gland or adrenalectomy does not abolish the NGF release. Corticotropic hormones do not induce NGF increase in the blood. Daily administrations of highly purified NGF (3 micrograms per g of body weight) result in a considerable increase in the volume of adrenal glands. These findings are unequivocable evidence for a physiological role of the mouse salivary glands as a major source of blood NGF. PMID- 3090555 TI - Impaired biliary secretion of immunoglobulin A in vitamin A-deficient rats. AB - The effect of vitamin A deficiency on biliary secretion of IgA was investigated. Rats used in this study were rendered vitamin A deficient following withdrawal of retinoic acid from the diet of retinoate-cycled animals. This procedure allows a precise control of both the onset of deficiency and dietary protein-energy input. Defective synthesis and transport of IgA antibodies into the bile was evident when vitamin A-deficient rats (A-) were immunized by injections of either Brucella abortus or sheep red blood cells directly into the Peyer's patches. Antibody titers in the bile of A- animals were significantly lower than those of A+ controls (P less than 0.01). These A- rats also had significantly lower levels of total IgA in the bile compared with A+ controls (P less than 0.05). Moreover, the transport of labeled rat IgA injected intravenously was adversely affected in these animals. These results, together with our previous report on the impaired intestinal antibody in A- rats, clearly indicate that vitamin A deficiency interferes with the transport of IgA antibodies into the bile of these animals. PMID- 3090554 TI - Hormonal regulation of the release of plasminogen activators and of a specific activator inhibitor from endometrial tissue in culture. AB - Two types of plasminogen activator (PA), t-PA (tissue type) and u-PA (urokinase type), are released from endometrial tissue in organ culture, as judged by immunological identification and molecular weight. Addition of estradiol to the medium greatly enhanced the release of u-PA, whereas that of t-PA was not low. Addition of progesterone, on the other hand, after priming of the endometrial tissue with estradiol, resulted in a much lower release of both types of PA. This pattern of PA release in response to hormonal stimulation in vitro agrees with previous observations of the PA activity of endometrial secretion in vivo. Endometrial tissue also released a PA inhibitor with molecular weight of approximately 50,000, which complexed both t-PA and u-PA. In cultures stimulated with estradiol the amount of free u-PA increased gradually during incubation and minor amounts of free t-PA appeared after 4-6 days culture. The amount of complexes, and thus the amount of PA inhibitor also increased under influence of estradiol. In cultures stimulated with progesterone, on the other hand, only minor amounts of free u-PA and no free t-PA was detected. The inhibitor might be of either the endothelial or the placental type, or both. PMID- 3090556 TI - Lactate oxidation by three segments of the rabbit proximal tubule. AB - Oxidation of [U14C]lactate to 14CO2 was measured in vitro, in nonperfused anatomically defined segments of rabbit proximal tubule (S1, proximal convoluted, and S2 and S3, proximal straight tubules). The rate of lactate oxidation was similar in S2 and S3 segments, and within the range of lactate oxidation rates measured in vivo. In contrast, the oxidation rate of S1 segments was significantly lower than that of S2 or S3. In proximal straight tubules, lactate oxidation was inhibited by incubation at 0 degrees C, or by application of 1 mM ouabain. To determine if the rate of transepithelial transport affected the rate of lactate oxidation, lactate oxidation was measured in proximal straight tubules after the lumen had been opened by perfusion with Ringer's containing 10 mM polyethylene glycol. No difference in lactate oxidation rate was observed between tubules with patent lumina and nonperfused tubules. These results suggest that the various segments of the renal proximal tubule have different metabolic characteristics, and that the rate of substrate oxidation is related to the activity of the Na+, K+-ATPase. PMID- 3090557 TI - Effect of controlled ventilation on renal and splanchnic blood flows during severe arterial hypoxia. AB - The present study was undertaken to evaluate the extent that the lung inflation reflex attenuates vasoconstrictor responses in renal cortex and splanchnic beds during severe arterial hypoxia. Hypoxia was induced by inspiration of a 3-5% oxygen gas mixture in three groups of chloralose-anesthetized dogs: Group I, free breathing; Group II, controlled ventilation; Group III, free breathing with arterial PCO2 held constant. Regional vascular conductances (VC) were calculated from regional blood flows measured with 15-microns radioactive microspheres. In Group I, hypoxia caused marked hyperventilation, which was accompanied by no significant change in VC in renal cortex, and by reductions in VC in spleen ( 36%), pancreas (-56%), and duodenum (-28%). In Group II, hypoxia caused reduction in VC in renal cortex (-70%), and reductions in VC in spleen, pancreas, and duodenum similar to those in Group I. In Group III, hypoxia again caused marked hyperventilation, but reductions in VC in renal cortex, spleen, pancreas, and duodenum were similar to those in Group II. Results indicate that during severe arterial hypoxia activation of lung inflation reflex does not attenuate or reverse vasoconstriction in renal cortex, spleen, pancreas, and duodenum. PMID- 3090558 TI - Prevention of neural myoinositol depletion in diabetic rats by aldose reductase inhibition with tolrestat. AB - The effect of the aldose reductase inhibitor tolrestat on the sugar and polyol contents in the sciatic nerve was investigated in male Wistar and Sprague-Dawley rats rendered diabetic with streptozocin. At a daily oral dose of 5 mg/kg, given for 10 days before and for 14 days after streptozocin injection, tolrestat completely prevented the accumulation of sorbitol and the depletion of myoinositol. PMID- 3090559 TI - Antitumor activity in a rat mammary adenocarcinoma: the effect of cyclooxygenase inhibitors and immunization against prostaglandin E2. AB - Female Fischer 344 rats bearing the R3230AC mammary tumor were treated with three different inhibitors of cyclooxygenase--indomethacin, ibuprofen, and flurbiprofen (5 mg/kg body weight). After three weeks, the weight and volume of tumors from treated animals were smaller than those of control rats. Rats bearing the same tumor but immunized against PGE2 conjugated to bovine serum albumin showed similar trends in tumor growth inhibition. Thus we conclude that PGE2 plays an important role in the establishment and growth of the R3230AC mammary tumor. PMID- 3090560 TI - Coronary vasoactivity of four 7,13-bridged analogs of arachidonic acid. AB - Four newly synthesized 7,13-bridged arachidonic acid analogs which have been shown to exert 5-lipoxygenase inhibitory activity were studied in isolated perfused cat coronary arteries. The two dehydro analogs constricted and the two non-dehydro analogs dilated the coronary arteries. None antagonized LTD4 induced constriction. Thus there is no direct connection between lipoxygenase inhibition and leukotriene inhibition or vasoactivity. PMID- 3090561 TI - Effects of dipyridamole, nifedipine, verapamil, hydralazine and propranolol on the formation of prostacyclin and thromboxane in a coupled system of platelets and aorta. AB - The effects of some vasodilatory (dipyridamole, nifedipine, verapamil) and antihypertensive (hydralazine, propranolol) drugs on the metabolism of exogenous arachidonic acid (AA), and on the production of thromboxane from endogenous AA stores were examined. In a coupled system of platelets and rat aorta, dipyridamole (100 microM), nifedipine (300 microM) and hydralazine (250 microM) potentiated the formation of 6-keto-F1 alpha from exogenous AA. Hydralazine in this system reduced the formation of TxB2. At higher concentrations the drugs (dipyridamole 500 microM; hydralazine 1 mM, verapamil 2mM; propranolol 2mM) were effective in reducing the formation of TxB2. Moreover, the drugs at lower concentrations produced reduced amounts of TxB2 in clotting blood. A dose dependent inhibition of platelet aggregation induced by ADP, epinephrine, collagen and arachidonate was observed with these drugs. The results demonstrate that some of the beneficial effects of the drugs in the cardiovascular system can be explained on the basis of their effects on platelet aggregation and on AA metabolism. PMID- 3090563 TI - Effect of serum on the metabolism of exogenous arachidonic acid by phagocytic cells of the mouse thymic reticulum. AB - Phagocytic cells derived from the mouse thymic reticulum (P-TR) were used to study the effect of serum on the metabolism of arachidonic acid (AA). After labeling with (14C)-AA in the presence of 10% serum, we failed to detect in the culture medium the presence of significant amounts of radiolabeled prostaglandins. In contrast, when the labeling period was carried out in serum free medium, we observed the secretion of both cyclooxygenase and lipoxygenase derivatives. In addition, the pattern of arachidonate incorporation into cell lipids was different in the two culture conditions. In the presence of serum, the great majority of the radioactivity was found associated with phospholipids, whereas in serum-free medium, almost 50% of the incorporated fatty acid was associated with triglycerides. Since serum albumin is known to play a major role in the control of fatty acid uptake, we have studied the effect of the addition of 2% BSA to cells prelabeled in the absence of serum. This treatment switches the patterns of metabolite release and lipid labeling towards those of serum treated cells. In addition, we showed that the effects of glucocorticoids on AA release differ markedly according to the composition of the culture medium. PMID- 3090562 TI - Dietary fat and cholesterol modification of rat abdominal aorta prostacyclin and leukotriene production (in vitro). AB - Groups of weanling male Sprague-Dawley rats fed formulated diets containing 15% by weight of corn oil (CO), linseed oil (LNO), or corn oil plus 1% cholesterol and 0.25% cholic acid (CH-CH) were sacrificed after 8 weeks and the aortas removed. Three mm length cross-sectional rings were cut from the distal abdominal aorta segment and incubated in either Tris buffer (pH 7.4, 37 degrees, 10 min.) for measurements of prostacyclin as 6-Keto-prostaglandin in F1 alpha (6-Keto-PGF1 alpha) or Tris buffer plus 10 microM ionophore A23187 for measurement of leukotriene C4 (LTC4) production using radioimmunoassay (RIA) procedures. 6-Keto PGF1 alpha production was greater (p less than 0.01) in the CO than in the LNO and CH-CH fed rats by 54% and 40% respectively. LNO diets significantly lowered LTC4 production when compared to tissues from CO-fed rats (p less than 0.05). LTC4 production by tissues from the CH-CH-fed animals was lower than tissues from CO-fed animals, however, the difference failed to reach levels of significance because of data spread and the number of tissues. Tissues from the CH-CH-fed and LNO-fed rats were significantly different than those of the CO since LTC4 formation was high relative to 6-Keto-PGF1 alpha production (LTC4/6-Keto-PGF1 alpha). These results suggest distinctive effects of dietary fat and cholesterol on the syntheses of vasoactive eicosanoids that may be relevant to arterial tissue physiology and pathology. PMID- 3090564 TI - Chronic effects of clonazepam, phenytoin, ethosuximide, and valproic acid on learning in pigeons as assayed by a repeated acquisition procedure. AB - The acute and chronic effects of the antiepileptic drugs clonazepam (0.06, 0.13, and 0.25 mg/kg), phenytoin (2.5, 5, and 7.5 mg/kg), ethosuximide (40, 80, and 120 mg/kg), and valproic acid (40, 80, and 120 mg/kg) were evaluated in pigeons responding under a repeated acquisition procedure. At certain doses, acute administrations of all drugs impaired learning (i.e., increased errors) and reduced rate of responding. Appreciable tolerance developed to these effects with chronic exposure, although the physiological mechanism responsible for this outcome is unknown. PMID- 3090565 TI - Hypothyroidism leads to increased dopamine receptor sensitivity and concentration. AB - Rats treated with iodine-131 were confirmed to be hypothyroid by their reduced baseline core body temperatures, reduced serum thyroxine concentrations and elevated serum thyroid stimulating hormone concentrations. When hypothyroid rats were compared to euthyroid controls they were more sensitive to the effects of apomorphine (1.0 mumol/kg) on stereotypy, operant responding and body temperature and showed a smaller reduction in locomotor activity after injection of haloperidol (0.25 mumol/kg). Receptor binding studies on striatal homogenates indicated that hypothyroid rats had increased concentrations of D2 dopamine receptors but there was no change in the affinity. It is concluded that hypothyroidism increases dopamine receptor sensitivity by increasing receptor concentration. PMID- 3090566 TI - Chronic ethanol administration inhibits calmodulin-dependent Ca++ uptake in synaptosomal membranes. AB - Chronic ethanol administration inhibits ATP-dependent Ca++ uptake in a preparation of synaptic membranes prepared from mice following 1, 4 and 7 days of ethanol exposure in a liquid diet. Addition of calmodulin (2.5 micrograms) to membranes from mice receiving the control diet produced a slight stimulation of ATP dependent Ca++ uptake. Membranes from ETOH treated mice exhibited reduced capacity to take up Ca++ in ATP-dependent fashion. When calmodulin was added to membranes isolated from mice receiving ETOH on Days 1, 4 and 7 ATP-dependent Ca++ uptake was significantly stimulated (p less than 0.01) compared to (1) ETOH treated membranes in absence of calmodulin, and (2) control membranes. Behavioral tolerance as estimated by bar holding technique was found to be 25, 65 and 91 percent complete for Days 1, 4 and 7 respectively. These studies demonstrate that continued exposure of mice to ethanol via consumption of an ethanol containing liquid diet inhibits one of the mechanisms involving the cytosolic buffering of intracellular Ca++ in nerve terminals. This biochemical effect seen in parallel with the development of tolerance to ethanol impairment of bar holding suggests that increased cytosolic Ca++ may aid in central nervous system adaptation to ethanol. PMID- 3090567 TI - Long-term effects of TRH administration on food intake and body weight in the rat. AB - The effect of long-term TRH administration through drinking water (0.2 mg/ml) on food and water intake and body weight has been studied in three groups of female rats: (1) thyroidectomized, (2) thyroidectomized receiving daily 250 micrograms/kg of L-T4, (3) sham-operated. Treatment with oral TRH for 30 days decreased body weight and increased food intake in sham-operated rats. No TRH effects on body weight or food consumption were observed in either of the other groups of thyroidectomized rats. TRH administration increased circulating T3 levels in sham-operated animals, but had no effects in either hypo- or hyperthyroid, thyroidectomized rats. It can be concluded that the TRH-induced increase on food intake is mediated through the pituitary-thyroid axis. PMID- 3090568 TI - Influence of magnesium on norepinephrine-and histamine-induced contractions of pulmonary vascular smooth muscle. AB - We examined the effects of magnesium on contractile responses of the rabbit pulmonary artery. The contractile force was determined, after applications of norepinephrine or histamine, in a normal or Ca++-free solution containing 0 mM Mg++ or 1.2 mM Mg++. In a normal solution, Mg++ increased the EC50 value for histamine, but did not alter the EC50 value for norepinephrine or the maximum force induced by norepinephrine or histamine. Contractile responses to norepinephrine and histamine were equally reduced by a Ca++-free, Mg++-free solution, and were further reduced by a Ca++-free solution containing Mg++, but with a greater reduction in the response to histamine than in the response to norepinephrine. The results indicate that in the pulmonary artery, Mg++ alters the sensitivity to histamine but not to norepinephrine, and may differentially inhibit bound Ca++ release by norepinephrine and histamine. PMID- 3090569 TI - Glucuronidation of 1-naphthol in nuclear and microsomal fractions of the human intestine. AB - The glucuronyl transferase activity was measured with 1-naphthol as a substrate in nuclear and microsomal fractions of the human intestinal mucosa. The mucosa was obtained from different parts of the intestine. The rate of 1-naphthol glucuronidation ranged between 0.70 and 1.26 nmol/mg/min (nuclear fraction) and 0.21 and 0.54 nmol/mg/min (microsomal fraction). The average (+/- SEM) of the nuclear/microsomal ratios of the glucuronyl transferase was 2.48 +/- 0.19. The epoxide hydrolase activity towards styrene oxide was measured in the same subcellular fractions; it was undetectable in the nuclear fraction, whereas it was 0.46 +/- 0.04 nmol/mg/min (mean +/- SEM) in the microsomal fraction. The glucuronyl transferase activity was also measured in nuclear and microsomal fractions of the human liver. The activity (mean +/- SEM) was 1.14 +/- 0.21 nmol/mg/min (nuclei) and 5.00 +/- 0.80 (microsomes). The average of the nuclear to microsomal ratios (mean +/- SEM) was 0.32 +/- 0.03. PMID- 3090570 TI - Comparison of recent codes of practice for high-energy photon dosimetry. AB - Absorbed dose values were determined under the reference conditions in a phantom irradiated by high-energy photon beams with quality varying between 60Co gamma rays and 25 MV X-rays, using four commonly employed types of ionisation chamber. The ionisation chamber readings were converted to absorbed dose values applying the recent NACP, AAPM and SEFM Protocols and the revised HPA Code of Practice. The AAPM and SEFM Protocols gave consistent results for the four types of chamber whereas the NACP Protocol should be adapted to take the differences in chamber wall material and chamber dimensions into account. Absorbed dose values determined with the standard chamber and procedure recommended in the HPA Code of Practice show good agreement, within 0.8%, with absorbed dose values obtained using the AAPM and SEFM Protocols. PMID- 3090571 TI - Accuracy of PET RCBF measurements: effect of time shift between blood and brain radioactivity curves. AB - Analytic expressions were derived for estimating the error in PET RCBF measurements associated with the time lag between brain and blood radioactivity following bolus H2(15)O injection and during non-steady-state CO15O inhalation. This lag time reflects the physiological difference in arrival times of 15O activity at brain and radial arterial sampling site as well as the experimentally introduced resistance to flow offered by the arterial catheter/stopcock assembly. Multiple measurements of this time lag ranged between 1 and 10 s. For non-steady state CO15O PET measurements, estimated errors in RCBF ranged from 0.02 to 30% for delays of 2-8 s and scan lengths of 30-180 s. In the range 20-100 ml min-1 per 100 g, variations in RCBF only marginally affected these errors. Errors increased with longer delays but decreased sharply with scan durations greater than 60 s. For 30-180 s scans, even larger errors are associated with the H2(15)O injection technique (peak blood activity at 10 s): 1-60% for delays of 2-8 s. A 'slow' bolus peaking at 20 s decreased the error by 40%. For the H2(15)O method it is essential to estimate the time shift to within 2 s if accurate flow measurements (error less than 5%) are to be obtained from 40-60 s scans. PMID- 3090572 TI - Changing health care environments--implications for physical therapy research, education, and practice. A special communication. AB - This article explores changes in the organization and management of the health care system and their impact on physical therapy services. It discusses why and how the demand for physical therapy services is changing and how the practice of physical therapy is being altered. The impact of change on physical therapists is presented in terms of such effects as stress, burnout, absenteeism, and job turnover. The article develops approaches that physical therapists, individually and collectively, can pursue to position themselves more effectively in a changing health care environment. These are opportunities as well as constraints. The theme that is presented is how to adapt to change in a positive and proactive manner. PMID- 3090573 TI - Cerebrospinal fluid pressure of anaesthetized rats during intracerebroventricular infusion. AB - Increases in cerebrospinal fluid pressure (CSFP) were measured in the lateral ventricle in barbiturate anaesthetized male Sprague Dawley rats during intracerebroventricular (IVT) infusions into the contralateral ventricle. IVT infusions of isotonic artificial CSF (art-CSF) solutions at 10 and 38 microliters/hr increased mean CSFP from control preinfusion level of 3.6 cm H2O to 4.6 cm H20 (n.s.) and 5.2 cm H2O (p less than 0.01) respectively with CSFP appearing to attain equilibrium after 30-60 min of infusion. IVT infusion of hyperosmolar art CSF solutions (saccharide and salt solutions of approximate 1000 mOsm/kg) at 38 microliters/hr resulted in a larger increase of CSFP which equilibrated at 8.5 cm H2O (p less than 0.001) after 90 min of infusion. It is suggested that on the basis of CSFP measurements in these and other experiments cited that IVT infusions be run at infusion rates of less than 40 microliters/hr to ensure minimal physiological change. PMID- 3090574 TI - Aging and the perception of nasal irritation. AB - Three types of measurement were employed to assess the effects of aging on nasal irritation (common chemical sense). These were measurement of detection threshold of CO2 mixed with air, measurement of the threshold concentration of CO2 that causes a transient reflex apnea, and measurement of the suprathreshold perceived strength of five levels of CO2 by the method of magnitude matching. Ancillary measurements included nasal airflow resistance and magnitude matching of an odorant (1-butanol). Twenty elderly (67 to 93) and twenty young persons (19 to 31) served as subjects. The young and elderly gave no evidence of average difference in detection threshold. In contrast, the elderly group showed a strong elevation of the threshold of apnea and a marked weakening of perceived CO2 suprathreshold strength. CO2 and butanol approximated power functions of concentration level, functions for the elderly being depressed relative to those for the young. Although the elderly had on the average slightly higher nasal resistance than the young, the differences played at most a minor role in the perception of nasal stimuli. PMID- 3090576 TI - The nucleotide sequence of the tetracycline resistance gene of plasmid pNS1981 from Bacillus subtilis differs from pTHT15 from a Thermophilic bacillus by two base pairs. PMID- 3090577 TI - [Developmental peculiarities of brain-damaged children]. PMID- 3090575 TI - New plasmid expression vectors for Bacillus subtilis. AB - The construction of new cloning vectors for Bacillus subtilis is described. They are derived from the in vitro joining of parts of pE194 and pUB110 DNAs. Their common feature is to present a cloning site immediately after the promoter and ribosome binding site of the erythromycin resistance gene, allowing the insertion and expression of either sticky or blunt ended DNA fragments coding for any heterologous gene. The cloning and expression of Escherichia coli beta-lactamase and EcoRI methylase are given as examples. The enzymes are efficiently synthesized by B. subtilis cells. PMID- 3090578 TI - [Epileptic psychosis and nonconvulsive status epilepticus with ictal bradycardia and asystole]. AB - Case report of a 35 years old patient, who, without previous history of epilepsy, within two years experienced two long-lasting psychotic episodes due to non convulsive status epilepticus with complex partial seizures. During the second psychotic episode she developed ictal vegetative phenomena such as profuse sweating, flush, apnoea, and, above all and most alarming, periods of severe bradycardia and asystolia with clinical signs of syncope. Ictal asystolia, though being an uncommon sing of epileptic seizures, may be one cause of sudden unexpected death in epileptics. PMID- 3090579 TI - Low dose potency of lithium in antidepressant augmentation. PMID- 3090580 TI - MMPI results associated with abnormal responses to the DST and TRH tests. PMID- 3090581 TI - Clinical psychology and the medical model. PMID- 3090582 TI - Evaluation of L-tryptophan for treatment of insomnia: a review. AB - Sleep laboratory and outpatient studies of the hypnotic efficacy of the amino acid L-tryptophan are reviewed, with particular emphasis on evaluation of therapeutic effectiveness in the treatment of insomnia. In younger situational insomniacs, whose sleep problem consists solely of longer than usual sleep latencies, L-tryptophan is effective in reducing sleep onset time on the first night of administration in doses ranging from 1 to 15 g. In more chronic, well established sleep-onset insomnia or in more severe insomnias characterized by both sleep onset and sleep maintenance problems, repeated administration of low doses of L-tryptophan over time may be required for therapeutic improvement. In these patients, hypnotic effects appear late in the treatment period or, as shown in some studies, even after discontinuation of treatment. The improvement in sleep measures post-treatment has given rise to use of a treatment regimen known as "interval therapy", in which L-tryptophan treatment alternates with an L tryptophan-free interval until improvement occurs. The absence of side effects and lack of development of tolerance in long-term use are important factors in the decision to embark upon a trial of L-tryptophan treatment. In addition, L tryptophan administration is not associated with impairment of visuomotor, cognitive, or memory performance, nor does it elevate threshold for arousal from sleep. PMID- 3090583 TI - State-dependent learning effects with a combination of alcohol and nicotine. AB - An experiment was carried out to investigate whether nicotine ingestion (via cigarette smoking) interacted with alcohol (vodka and tonic) in its effect on state-dependent learning (SDL) in humans. On Day 1 of the 2-day experiment 24 subjects were required to learn a simple route map previously found to be SDL sensitive with alcohol. All subjects ingested 0.66 g alcohol/kg body wt. and smoked two medium tar cigarettes (average nicotine content 1.4 mg). Twenty-four hours later, subjects attempted recall under one of the following drug states; (i) alcohol and nicotine (A + N); (ii) alcohol and smoking placebo (A + O); (iii) Nicotine and placebo drink (O + N); and (iv) no drugs (O + O). Highest recall scores were observed in the A + N subjects, with O + N and O + O subjects recalling the least. A + O subjects had intermediate recall performance. Thus the combination did produce a clear SDL effect, with alcohol possibly contributing the major influence. PMID- 3090584 TI - Bromocriptine and apomorphine stimulation of cortisol secretion in conscious dogs; evidence for a stimulatory site located outside the blood brain barrier. AB - IV injections of the dopamine receptor agonists bromocriptine (0.1 mg/kg) and apomorphine (0.05 mg/kg) induced rapid and long-lasting increases of cortisol levels as measured by RIA in peripheral venous plasma of conscious dogs. Pretreatment with dopamine receptor antagonists which do not readily penetrate the blood brain barrier (domperidone, halopemide, sulpiride) abolished the release responses induced by the dopamine agonists. These results suggest that the dopamine receptor agonists stimulate cortisol release at a site located outside the blood brain barrier. In addition, some dopamine receptor antagonists (haloperidol, chlorpromazine, milenperone) were shown to cause a rapid and long lasting increase of cortisol levels. PMID- 3090585 TI - Chronic treatment with Ro 15-1788 distinguishes between its benzodiazepine antagonist, agonist and inverse agonist properties. AB - Ro 15-1788 (flumazepil) is an imidazodiazepine that is able to antagonise most of the behavioural actions of the benzodiazepines, as well as having some intrinsic effects. Acute administration of Ro 15-1788 (10 mg/kg) decreases social interaction between male rats and elevates exploratory head-dipping. After 5 days of pretreatment there was tolerance to the former effect, although Ro 15-1788 retained its ability to antagonise the effects on social interaction of the beta carboline, FG 7142. Ro 15-1788 also retained its ability to elevate head-dipping: additionally, the chronically-treated rats had elevated motor activity and rearing scores. The acute effects of lorazepam in the holeboard were unchanged by chronic pretreatment with Ro-15-1788. The plasma and brain concentrations after acute administration of lorazepam were unchanged following chronic administration of Ro 15-1788. After chronic treatment the brain concentrations of Ro 15-1788 were unchanged. It is unlikely that pharmacokinetic factors could underlie the different behavioural changes following chronic treatment. PMID- 3090586 TI - Behavioural tolerance to arecoline in rats: cross-tolerance to oxotremorine and prevention by pretreatment with atropine. AB - In two experiments tolerance development to the effects of arecoline on operant responding for a water reward was shown to be dose-dependent, complete tolerance developing to a daily dose of 4 mg/kg, but only partial tolerance developing to a daily dose of 8 mg/kg. However, rats chronically treated with the higher dose of arecoline were least affected by a challenge dose of oxotremorine (0.2 mg/kg); i.e. the high dose group exhibited the greatest cross-tolerance to oxotremorine. Moreover, atropine (4 mg/kg) pretreatment prior to arecoline (4 mg/kg) prevented cross-tolerance to oxotremorine, indicating that dispositional mechanisms are unlikely to be involved in tolerance to arecoline. PMID- 3090587 TI - Effects of repeated administration of the monoamine oxidase inhibitor phenelzine on the discriminability of d-lysergic acid diethylamide (LSD) and 1-(m trifluoromethylphenyl) piperazine (TFMPP). AB - Rats trained to discriminate d-lysergic acid diethylamide (LSD; 0.08 mg/kg) or 1 (m-trifluoromethylphenyl) piperazine (TFMPP; 0.8 mg/kg) were treated with the monoamine oxidase inhibitor (MAOI) phenelzine (10 mg/kg/day) for 7 days. After a 24 h "washout" period, they were challenged with the training drug (and dose) or saline, during extinction test sessions. Following 0.08 mg/kg LSD, LSD-trained rats responded primarily on the saline lever (29% drug-appropriate responding) while, after TFMPP (0.8 mg/kg), TFMPP-trained animals responded on the drug lever (75% drug-appropriate responding). These preliminary data suggest that, if serotonin receptors are involved in the behavioral effects of TFMPP, these receptors differ from those involved in the effects of LSD. PMID- 3090588 TI - Memory performance by mild hypertensives following beta-adrenergic blockade. AB - Previous experiments have reported deficits in cognitive performance following the administration of beta-adrenoceptor antagonists. These deficits have not appeared consistently, however, and it is not clear from previous studies whether changes in the central nervous system, rather than end-organ functioning, are responsible. The present experiment investigated the effects of beta blockade in a memory-search paradigm that distinguished the relatively central process of memory comparison from the more peripheral processes of stimulus encoding and response selection. Twenty-six adult men with mild essential hypertension received either a placebo or a beta blocker (atenolol or propranolol) for 2 weeks. Although beta blockade did occur in the active drug groups, there were no significant effects of the drugs on memory-search performance. PMID- 3090590 TI - Tolerance to hypothermia induced by ethanol depends on specific drug effects. AB - Two experiments were conducted to test the hypothesis that tolerance to the hypothermic effect of ethanol fails to develop if rats are denied the unconditional stimulus represented by hypothermia. In both experiments, rats were injected with either ethanol (1.9 or 2.5 g/kg) or saline and given microwave hyperthermia (MHT) to offset the hypothermic effect of the drug or sham-MHT. In one experiment, rats no longer demonstrated a hyperthermic response to a saline challenge after hypothermia was offset during 5 MHT treatment sessions. In a second experiment, rats prevented from becoming hypothermic did not develop tolerance to the hypothermic effect of ethanol due to MHT treatment, but did become tolerant to the ataxic effects of ethanol, which were unaffected by MHT. Results suggest that rats must experience the specific consequences of a drug to become tolerant to that effect. PMID- 3090589 TI - Striatal dopamine uptake asymmetries and rotational behavior in unlesioned rats: revising the model? AB - The relationship between circling behavior and the dopaminergic (DA) innervation of the striatum was investigated in rats. Vmax for DA uptake in crude mitochondrial (P2) fractions was used as a measure of the density of striatal DA terminals. Females, as a group, rotated away from (i.e., contralateral to) the side containing the higher Vmax for DA uptake, while there was a nonsignificant trend in the opposite direction for the males. Further analysis suggested that in both sexes there are two kinds, or populations, of rats: those with their turning biases directed away from (Contra greater than Ipsi rats), and those with their turning biases directed towards (Ipsi greater than Contra rats) the side containing the striatum with the higher Vmax for DA uptake. Evidence supporting this two-population hypothesis includes: (a) For both groups of rats the slope of the best fit linear relationship between the contralateral/ipsilateral Vmax asymmetry and rotational behavior is equal in magnitude, though opposite in sign; (b) Mean contralateral Vmax is greater for the Contra greater than Ipsi rats than for the Ipsi greater than Contra rats, while the mean ipsilateral Vmax is virtually identical for the two groups; (c) The two groups of rats can be differentiated behaviorally on the basis of a measure of total lateralized activity, % turning. In addition, the Km for DA uptake for the females (1.81 +/- 0.07 X 10(-7) M) was found to be significantly greater than for the males (1.51 +/- 0.04 X 10(-7) M; P less than 0.005). PMID- 3090591 TI - Facilitation of stimulatory effect of chlordiazepoxide-amphetamine combination by subacute administration of chlordiazepoxide in mice. AB - Spontaneous locomotor activity was tested in CD-1 mice receiving subacutely (for 4 days) chlordiazepoxide (10 mg/kg) and then treated with d-amphetamine (0.5 or 1 mg/kg) and various doses of chlordiazepoxide (2.5, 5 or 10 mg/kg) separately or in combination. Chlordiazepoxide pretreatment enhanced the stimulatory effect of the chlordiazepoxide-amphetamine combination. PMID- 3090592 TI - Facilitation of learning and state dependency with nicotine. AB - Two studies of nicotine and memory encoding were carried out using a state dependent design. The first experiment used cigarettes and involved memory for stimuli that could not be encoded phonemically or semantically. The results of this recognition study show that nicotine was facilitating the input of non phonemicably encodable and non-semanticably encodable information to storage and that nicotine produced state-dependent learning. The second study used nicotine tablets and involved memory for concrete words. The results of the free recall study show that nicotine produced state-dependent learning, that nicotine was facilitating the input of information to storage, but there was no evidence that associative processes had been changed by nicotine. These findings give no support for the suggestion that a cholinergic system in the brain is controlling the encoding of intrinsic cues relating to phonemic and semantic properties of things but not those involving mnemonic encoding by mental imagery, but rather that the cholinergic system is non-specifically involved in encoding. PMID- 3090593 TI - Strain difference in the effects of morphine on the rectal temperature and respiratory rate in male mice. AB - Effects of morphine on the rectal temperature and respiratory rate, and [3H]naloxone binding to brain membranes from seven brain regions were compared among six strains of male mice, including DBA/2N, C57BL/6N, BALB/c, C3H/HeN, A/J and ICR. The administration of 10 and 20 mg/kg doses of morphine HCl to these strains of mice decreased rectal temperature and respiratory rate. However, there was a significant strain difference in these two measures of the effect of morphine. The DBA/2N strain was the most sensitive in both measures of morphine action. The magnitude of hypothermia was positively correlated with respiratory depression among six strains of mice after the administration of 10 and 20 mg/kg morphine HCl, suggesting common mechanisms. Strain difference in naloxone binding in the brain regions could not explain that of the morphine responses, because there was no correlation between the intensity of morphine-induced hypothermia or respiratory depression and the regional [3H]naloxone binding for the mouse strains. PMID- 3090594 TI - Apomorphine anorexia: the role of dopamine cell body autoreceptors. AB - Anorectic effects of apomorphine were studied in a microstructural analysis paradigm. Systemic apomorphine reduced food intake by reducing both the rate of eating and the time spent eating. Peripheral administration of sulpiride reversed the apomorphine effect on both eating rate and eating time but central administration of this neuroleptic into the ventral tegmental area (VTA) selectively reversed the apomorphine effect on eating time, sparing eating rate. Administration of apomorphine directly into the VTA reduced eating time but not eating rate; the effect on eating time was blocked by peripheral sulpiride. The results imply that the two components of apomorphine anorexia result from actions at different sites. Effects of apomorphine on eating time appear to result from an action on DA cell body autoreceptors. The apomorphine effect on eating rate appears to be mediated elsewhere. PMID- 3090595 TI - Vasopressin has general rate-decreasing effects on schedules maintaining either high or low response rates. AB - Male and female Wistar rats were treated with different doses of vasopressin (0.05, 0.25, 1.25, 3.75 and 6.25 micrograms/kg) after responding had stabilized on either a differential reinforcement of low rate 15 s (DRL 15 s) or a differential reinforcement of high rate 0.75 s (DRH 0.75 s) schedule of reinforcement. Low to moderate doses of vasopressin did not affect response rates, response efficiency or the number of reinforcers obtained during vasopressin sessions on both the DRL and DRH schedules. Administration of 6.25 micrograms/kg vasopressin reduced low response rates and the number of reinforcers obtained during vasopressin sessions, but increased response efficiency. High response rates and response efficiency were reduced after administration of 3.75 and 6.25 micrograms/kg vasopressin, while the number of reinforcers obtained during vasopressin sessions was reduced at 6.25 micrograms/kg. Sex differences in the effects of vasopressin were not observed on either schedule. PMID- 3090596 TI - d-Amphetamine differentially affects low, but not high response rates of male and female Wistar rats. AB - The present experiments investigated sex differences in the effects of d amphetamine on schedule-controlled behavior. Male and female Wistar rats were exposed to either a differential reinforcement of low rate 15 s schedule, or a differential reinforcement of high rate 0.75 s schedule and challenged with different doses of d-amphetamine (0.2, 0.4, 0.8, 1.6 and 3.2 mg/kg). d Amphetamine in low to moderate doses increased low response rates. High doses of d-amphetamine decreased low and high response rates in both males and females. The response rate increasing effects of d-amphetamine on low baseline rates were significantly higher for females than for males. Sex differences for high baseline rates were not observed. The results of these experiments show not only that hormonal and neurochemical variables influence the effects of d-amphetamine administration on schedule-controlled behavior, but also that environmental contingencies maintaining the behavior can modify these effects. PMID- 3090597 TI - Instrumental analysis of ethanol-induced intoxication in human males. AB - A study was conducted to assess subjective reports of intoxication during the ascending phase of the plasma ethanol curve. Eighteen male social drinkers were divided into three groups and were given either placebo, 0.347 g/kg ethanol or 0.694 g/kg ethanol under double-blind conditions. Subjects reported levels of intoxication both instrumentally, by moving a joystick device, and verbally using an 11-point self-rating scale. Compared to placebo, ethanol produced significantly higher verbal self-rating scores, but there were no differences in the scores between the low- and high-dose ethanol groups. Instrumental responses of ethanol effects did, however, distinguish between the two ethanol treatments. All subjects who received ethanol reliably detected its effects when plasma ethanol levels reached 32 mg/dl, but only the subjects who received the high dose reported episodes of intense well-being or euphoria. Ethanol-induced euphoria occurred while plasma ethanol levels were rapidly rising, and was characterized by multiple, paroxysmal episodes that typically lasted about 3 min each. This study demonstrated that a continuously available instrumental response provided sensitive and reliable measures of rapidly changing behavioral states associated with ethanol-induced intoxication. PMID- 3090598 TI - Neuroendocrine effects of L-tryptophan and dexamethasone. AB - An infusion of L-tryptophan was administered twice to five healthy male volunteers, once after pretreatment with dexamethasone 1 mg the previous evening and once after no dexamethasone. Cortisol, prolactin, and growth hormone levels were measured, and the responses to L-tryptophan were compared with those seen after an infusion of L-threonine. L-tryptophan did not produce cortisol secretion after dexamethasone, but prolactin and growth hormone responses were noticed. The results demonstrate a stimulatory effect of L-tryptophan on prolactin and growth hormone secretion, and the former is facilitated by pretreatment with dexamethasone. PMID- 3090599 TI - Effect of l-tetrahydropalmatine on dopamine release and metabolism in the rat striatum. AB - In vivo voltammetric measurements of striatal extracellular DOPAC concentrations and of striatal DA release in combination with post-mortem analysis of striatal catechols were performed in the rat to study the effects on the nigro-striatal neurons of a Chinese neuroleptic, l-tetrahydropalmatine (l-THP), which is known to block post-synaptic dopaminergic receptors. l-THP injected at doses that cause sedation in rats and mice (5-10 mg/kg) induced a marked increase in post-mortem DOPAC levels (+250%), while no significant effect was observed on postmortem DA levels. The extracellular DOPAC concentration was increased to 155 +/- 9% of the control value after l-THP administration (1 mg/kg, IP). Further, an injection of l-THP (1 mg/kg, IP) induced an increase in extracellular DA concentration (220% of the basal value), reversed the decrease in extracellular DA concentration induced by apomorphine (0.05 mg/kg, SC) and enhanced the effects of the electrical stimulation of the nigro-striatal pathway. These results confirm that l-THP acts on the nigro-striatal neurons as a dopaminergic antagonist that can block both post- and presynaptic receptors. PMID- 3090600 TI - Scopolamine and the control of attention in humans. AB - Recent work with humans and animals has suggested that the cholinergic system plays an important role in the active control of attention. This study was designed to investigate the effects of scopolamine upon subjects' ability to utilize knowledge of the spatial probability bias in a display in the detection of briefly-presented target letters. Results showed a significant interaction between drug condition (scopolamine 0.9 mg versus Placebo) and target location probability, which indicated that detection of targets in high probability locations decreased under the drug, while detection in low probability locations increased. These results offer support for the notion that scopolamine reduces the efficiency of information encoding because it impairs the optimal utilization of attentional resources. PMID- 3090601 TI - Health implications of smokeless tobacco use. PMID- 3090603 TI - Smoking and smokeless tobacco use among adolescents: trends and intervention results. AB - Data from a 2-year study describe tobacco use trends, perceptions, and prevention effects for 1,281 5th and 6th graders enrolled in 12 randomly selected Washington State elementary schools. Youths were pretested, then randomly divided by school into skills, discussion, and control groups. Preventive intervention curriculums for the skills and discussion groups included age-relevant information on smoked and smokeless tobacco use, peer testimonials, debates, games, and homework. Youths in the skills group also learned communication and problem-solving methods for handling difficult situations around tobacco use. Following intervention, youths were posttested, then retested semiannually for 2 years. During the 2-year study, three-quarters of all smokers and nonusers and half of all smokeless tobacco users maintained their statuses. Only 10 percent of all smokers and 3 percent of all smokeless users quit their habits. One in six reported new tobacco use, one-third of smokers began using smokeless tobacco, and two-thirds of all smokeless users began smoking during the study. Most youths at final measurement perceived smokeless tobacco as less of a health risk than smoking. Nearly one in two of all smokeless users intended to smoke, and two-thirds were actually smoking at 24-month followup. Both smoked and smokeless tobacco use rates increased in all groups, and youths in the skills intervention group consistently showed the lowest rates relative to the other groups. These findings demonstrate the potential of skills intervention methods for lowering tobacco use rates among adolescents. PMID- 3090604 TI - Socioeconomic factors and burn rates in persons hospitalized for burns in Massachusetts. AB - To assess the usefulness of routinely collected socioeconomic variables from the U.S. census in predicting burn incidence rates, burn rates and 25 socioeconomic variables were analyzed at the level of census tracts for the Boston Standard Metropolitan Statistical Area. The burn rates were based on data collected during the National Burn Demonstration Project and consisted of patients who sustained burns between July 1, 1978, and June 30, 1979, and who required inhospital care. Analysis of the data revealed strong associations between burn rates and six of the variables. The six variables were the percentage of families below the poverty level with a householder under age 65 years, the percentage of persons over 5 years of age whose residence in 1975 was a different dwelling but in the same county, the percentage of persons in the civilian labor force who were unemployed at the time of census enumeration, the average age of occupied dwelling units, the percentage of occupied housing units occupied on a rental basis, and the percentage of persons age 25 years or older who acquired some college education but did not complete college. Interpretation of the findings is not straightforward but seems to suggest that the previously observed association between poor socioeconomic status and increased burn risk for individuals can be quantified at the census tract population level. PMID- 3090605 TI - The "missing cases" of pleural malignant mesothelioma in Minnesota, 1979-81: preliminary report. AB - Malignant mesothelioma is a sentinel neoplasm for population exposure to asbestiform fibers. Public health officials may be alerted to temporal or spatial clustering of malignant mesothelioma through analyses of vital records, such as death certificates. Hence, the maintenance of the integrity of the vital statistics system, particularly the cause of death statement on the death certificate, is very important. The report by a northeastern Minnesota radiologist in January 1985 of an elevated prevalence of pleural plaques (related to asbestiform fiber exposure) to the Minnesota Department of Health resulted in an investigation of pleural malignant mesothelioma mortality trends in that area and in three other similar areas in the State. In that study, we noted that in several instances malignant mesothelioma (either intrathoracic or unspecified site) was listed on the death certificate in such a manner as to imply that the neoplasm was either a lung cancer or a malignancy of an unspecified site. The effect of this misclassification is to underestimate the mortality from malignant mesothelioma by fourfold to eightfold. Given the importance of malignant mesothelioma as a proxy for past asbestos exposure, it is necessary to determine the extent of such misclassification for all deaths in the United States. PMID- 3090606 TI - The nationalization of a disease: a paradigm? AB - The early history of the Federal involvement in Hansen's Disease reflects the history of the Public Health Service itself. As a young and aggressive institution, the Public Health Service sought out contagious, infectious diseases that threatened the public health. National resources and national coordination were needed to fight the likes of malaria, hookworm, or smallpox. The customary attack would consist of a field study, determination of the etiology, the method of transmission, and, then, perhaps, preventive measures. An eradication campaign would follow. Leprosy fit perfectly into the model--a disease of unknown etiology, an unknown method of transmission, thought to be highly contagious, and no known cure. The United States launched a major investigation in Hawaii, where the disease was prevalent and its victims conveniently segregated. The investigation failed. The Public Health Service then turned toward segregation and isolation as a way to fulfill its public health role. A bureaucracy was established around the idea that victims of leprosy must be incarcerated for the good of the public. The institutionalization of the Public Health Service and the philosophy upon which its treatment of leprosy was based proved difficult to change when researchers in the field made major scientific breakthroughs in the 1940s. The realization that the disease was only feebly contagious, activities of patient organizations, and pressure from the media and the Congress did not achieve as dramatic results as the sulfone drugs did. The Public Health Service moved, but slowly. What are the lessons in all of this?. PMID- 3090607 TI - Source of service and visit rate for family planning services: United States, 1982. AB - The factors that affect how women choose their source of family planning care and how often they go for such care were investigated in the National Survey of Family Growth. The survey is based on a national sample of women 15-44 years of age interviewed in 1982, 4,318 of whom had family planning visits in the last 3 years. In contrast, previous research has been based on small, nonrepresentative samples, usually in one or a few locations or limited to visits to either private doctors or clinics, but not both; been limited to teenagers; or had no multivariate analysis. This study overcomes those limitations. When other variables were controlled, race, income, and insurance coverage had important effects on provider choice; marital status was important for white women, but not for black women. Contraceptive method, insurance coverage, and race were important determinants of the frequency of family planning visits, independent of other variables. It is suggested that relative costs or ability to pay, confidentiality, knowledge of alternative sources, and convenience of location affect choice of provider and visit rates. PMID- 3090608 TI - Histopathology in tropical medicine: a perspective. AB - Histopathology may serve a wide spectrum of diagnostic purposes in tropical medicine other than for infectious and parasitic diseases. In addition, it is essential in defining new pathological entities and collecting statistical data on morbidity and mortality. It should also constitute a basic support for advancement and research in tropical diseases. For practical purposes, both histopathology and cytopathology are often more effective than clinical chemistry and microbiology in providing the clinician with a final diagnosis. They do not rely on complicated and delicate equipment, and the few reagents they require can be stored indefinitely. Formalin fixation permits most histological methods to be used, including special stains and immunohistochemistry. Formalin-fixed material can be examined several days after excision. Implementing pathology laboratories in tropical countries may constitute a practical, cost-effective approach to the planning of diagnostic services at the regional or district level. A fraction of the medical graduates in developing countries should be devoted to the staffing of these laboratories. PMID- 3090602 TI - Health consequences of using smokeless tobacco: summary of the Advisory Committee's report to the Surgeon General. AB - On March 25, 1986, the Surgeon General of the Public Health Service released a report that detailed the results of the first comprehensive, indepth review of the relationship between smokeless tobacco use and health. This review, prepared under the auspices of the Surgeon General's Advisory Committee on the Health Consequences of Using Smokeless Tobacco, is summarized in this article. In the United States, smokeless tobacco is used predominantly in the forms of chewing tobacco and snuff. During the past 20 years, the production and consumption of these products have risen significantly in marked contrast to the decline in smokeless tobacco use during the first half of the century. National estimates indicate that more than 12 million persons age 12 and older in the United States used some form of smokeless tobacco in 1985, and half of these were regular users. The highest rates of smokeless tobacco use occurred among adolescent and young adult males. Examination of the relevant epidemiologic, experimental, and clinical data revealed that oral use of smokeless tobacco is a significant health risk. This behavior can cause cancer in humans, and the evidence is strongest for cancer of the oral cavity, particularly at the site of tobacco placement. Smokeless tobacco use can also lead to the development of noncancerous oral conditions, particularly, oral leukoplakias and gingival recession. Further, the levels of nicotine in the body resulting from smokeless tobacco can lead to nicotine addiction and dependence. PMID- 3090609 TI - Rocky Mountain spotted fever in Georgia, 1961-75: analysis of social and environmental factors affecting occurrence. AB - For the period of 1961 through 1975, 10 geographic and sociologic variables in each of the 159 counties of Georgia were analyzed to determine how they were correlated with the occurrence of Rocky Mountain spotted fever (RMSF). Combinations of variables were transformed into a smaller number of factors using principal-component analysis. Based upon the relative values of these factors, geographic areas of similarity were delineated by cluster analysis. It was found by use of these analyses that the counties of the State formed four similarity clusters, which we called south, central, lower north and upper north. When the incidence of RMSF was subsequently calculated for each of these regions of similarity, the regions had differing RMSF incidence; low in the south and upper north, moderate in the central, and high in the lower north. The four similarity clusters agreed closely with the incidence of RMSF when both were plotted on a map. Thus, when analyzed simultaneously, the 10 variables selected could be used to predict the occurrence of RMSF. The most important variables were those of climate and geography. Of secondary, but still major importance, were the changes over the 15-year period in variables associated with humans and their environmental alterations. Detailed examination of these factors has permitted quantitative evaluation of the simultaneous impacts of the geographic and sociologic variables on the occurrence of RMSF in Georgia. These analyses could be updated to reflect changes in the relevant variables and tested as a means of identifying new high risk areas for RMSF in the State. More generally, this method might be adapted to clarify our understanding of the relative importance of individual variables in the ecology of other diseases or environmental health problems. PMID- 3090612 TI - The anaemia of malaria. PMID- 3090611 TI - The Head Start dental component: evaluation of an urban program. AB - To evaluate the dental portion of a Head Start Program, the investigators determined the degree of compliance in providing children aged 3-5 years with annual examinations, topical fluoride, followup care, and a dental curriculum for their classroom. The study included an audit of the children's health records, a clinical assessment of care needs, oral cleanliness, and restoration quality, and an evaluation in the last month of the school year. The evaluation procedures were standardized, and dual examiners were used for all assessments. Differences of opinion between examiners were settled immediately, and the consensus was noted in the evaluation record for the study. A review was conducted of the health records for the 564 children enrolled in eight Head Start centers in Dallas, TX. According to those records, 74 percent of the children had been examined. Nearly 24 percent had required dental care because of caries--the range among centers was 11 to 43 percent. Of the group requiring care, 85 percent had received all the care needed. With the use of World Health Organization criteria, a mean score of 2.47 for oral cleanliness was determined for a random sample of 178 children. This sample also exhibited 1.45 decayed and 1.18 filled deciduous teeth per child. Restoration quality was rated; 94 percent were judged to be acceptable by Ryge's criteria. At all the centers, the dental health curriculum met the program standards set for Head Start by the Public Health Service, Region VI. This investigation showed that the centers did not uniformly comply with the clinical care standards devised for Head Start by the Public Health Service, but they did provide dental services that otherwise might not be available to children enrolled at the eight centers. PMID- 3090610 TI - Integrating ophthalmological and optometric services in a VA hospital program. AB - Basic eye care has been available at the Veterans Administration Medical Center (VAMC), Northport, NY, for the past 20 years. The demand for these services increased as the mission of this medical center was broadened to include major medical and surgery services. Increased migration of veterans to Long Island and their subsequent aging further increased the demand for eye-vision care. Originally, primary eye-vision care was provided independently by optometry and ophthalmology services. There was unnecessary duplication of equipment and inappropriate utilization of providers. Consequently, the services provided were quite limited in scope and sophistication. Both patients and providers became disenchanted with this practice mode. In December 1983, the administration of the Northport VAMC approved the establishment of a coordinated eye-vision care program that integrates ophthalmological and optometric services in a matrix structure. Since the program became operational in April 1984, patient satisfaction has increased, the working relationships between optometrists and ophthalmologists have improved, the ophthalmology residency program has been upgraded, and the combined staff productivity has increased. PMID- 3090614 TI - The barium enema scout film: cost effectiveness and clinical efficacy. AB - The authors prospectively evaluated 1,001 consecutive double-contrast barium enema examinations to determine the efficacy of the preliminary film. The scout films were evaluated for the presence of unsatisfactory amounts of residual feces and clinically significant extracolonic abnormalities. The contrast studies were independently evaluated in a double-blind manner for satisfactory colonic preparation as well as extracolonic abnormalities. The routine use of the scout film resulted in an increase in health care charges and departmental costs. In addition, there was no significant increase in the detection of extracolonic abnormalities. Our data suggest that routine use of scout films prior to contrast studies is unnecessary, although selective use in some clinical situations may be justified. PMID- 3090613 TI - [The level and immunochemical characteristics of fibronectin in the plasma of irradiated rats]. AB - The electrophoretic and immunoelectrophoretic methods were used to study fibronectin of blood plasma of intact Wistar rats and of those exposed to 1-10 Gy radiation. The increase in the fibronectin concentration 3 days after irradiation was a function of radiation dose. Possible mechanisms of the hyperfibronectinemia development involving mechanisms of endogenous proteolytic fragmentation of glycoprotein, the increase in the protein synthesis and complexation and inhibition of the rate of fibronectin degradation and elimination are discussed. PMID- 3090615 TI - Clinical and experimental vasogenic edema: in vivo sodium MR imaging. Work in progress. AB - To investigate the sodium magnetic resonance (MR) imaging characteristics of acute vasogenic edema, an experimental canine model was developed. Vasogenic edema was produced in the hemisphere of the dogs by the intraarterial infusion of hypertonic mannitol (25%). This solution opens the blood-brain barrier, allowing the influx of water, electrolytes, and proteins into the brain. The main advantage of this model over the established "cold injury" model is the lack of associated brain necrosis. Two patients with chronic vasogenic edema secondary to well-circumscribed meningiomas also underwent MR imaging. The sodium signal was markedly elevated in both clinical and experimental studies of vasogenic edema fluid compared with signal in healthy brain tissue. Extracellular sodium associated with vasogenic edema displayed MR imaging characteristics similar to that of sodium in serum. There was a trend toward a shortened T2 in edema fluid secondary to the presence of serum macromolecules. PMID- 3090616 TI - Surface receptors and cell function. Proceedings of the Society for Topochemistry and Electron Microscopy of East Germany. 21-24 November 1984, Bad Berka. PMID- 3090617 TI - The shape change of erythrocytes: new approaches to an old problem. PMID- 3090618 TI - Membrane skeleton and diminution of transmembrane proteins and calmodulin in erythrocytic vesicles. AB - During preservation of erythrocytes vesicles are formed, the membranes of which do not contain membrane skeleton components (spectrin, actin). In comparison to the normal erythrocyte membrane (100%) the vesicle membrane exhibits significantly lowered amounts in band 3 protein (14-17%), sialic acid (30-40%), (Ca2+ + Mg2+)ATPase (6%) and (Na+ + K+)ATPase (28%). The losses in band 3 protein, glycophorin A (calculated from the decrease of sialic acid) and in the number of the intramembranous particles correspond to one another. The calmodulin concentration of the vesicles was estimated to be 35% that of the erythrocytes in maximum. The findings indicate a binding of these components to the membrane skeleton. The nature of the binding of the transmembrane proteins as well as the consequences of these results regarding the composition of the intramembranous particles are discussed. PMID- 3090619 TI - A simple method to obtain brain microtubule protein poor in microtubule associated proteins. AB - By use of high glycerol and sodium chloride concentrations a microtubule protein (MTP) from porcine brain can be isolated that contains only a small portion of microtubule-associated proteins (MAPs). This "NaCl-MTP" possesses assembly properties similar to chromatographically purified tubulin. PMID- 3090620 TI - Structures of liposome membranes as models for similar features of cytoplasmic membranes of bacteria. AB - To characterize a special kind of membrane structure, visible in the cytoplasmic membranes of a Streptomyces hygroscopicus strain, liposome membranes were prepared from their extracted lipid mixture and from their lipid fractions (phospholipids, glycolipids, neutral lipids) and investigated by freeze-fracture electron microscopy. Liposome membranes made of the extracted lipid mixture reveal this special membrane structure, named wafer structure, from its regular pattern of bulges (30-40 nm in diameter). That is the proof that this membrane feature is a lipid structure. Liposome membranes prepared from the lipid fractions show the wafer structure if they are made of the phospholipid fraction only or in combination of this fraction with one or both of the other lipid fractions, indicating that wafer structure formation is primarily connected with the phospholipid content of the membranes. The glycolipid- and neutral lipid fractions amplify this phospholipid structure only. Additional to the wafer structure a raspberry structure with bulges of 55-65 nm in diameter is visible in some case. Obviously both structures are related. PMID- 3090621 TI - Histochemical demonstration of membrane-bound acetylcholinesterase: a methodological consideration on Koelle's copper thiocholine reaction and on Karnovsky's copper ferrocyanide reaction. AB - On the basis of own methodological investigations the reaction mechanisms of the methods of Koelle and Friedenwald (1949) and Karnovsky and Roots (1964) are described. Some modifications of these two methods are proposed. PMID- 3090622 TI - [Quantitative histochemical investigations on the demonstration of soluble and membrane bound acetylcholinesterase in the optic tectum of the rudd (Scardinius erythrophthalmus)]. AB - With the aid of the method of Karnovsky and Roots (1964) which was adapted to the semi-permeable membrane technique and a scanning recording method the relative activity of soluble and membrane bound AChE as well as the influence of fixation with 5% paraformaldehyde on the enzyme activity was investigated quantitative histochemically in the tectum opticum of the rudd. Approximately 38% of the AChE activity which can be demonstrated in the whole tectum opticum on native untreated cryostat sections are puffer-soluble and only 68% are detectable after fixation. The influence of both puffer and fixation pretreatment is different in the several layers of this brain structure. PMID- 3090623 TI - How informative is the cytochemical demonstration of adenylate cyclase? PMID- 3090624 TI - Receptors for erythrogenic toxin A of Streptococcus pyogenes on human peripheral blood lymphocytes and other blood cells. AB - The binding of erythrogenic toxin A (ETA) of group A streptococci on human peripheral blood cells was demonstrated light- and electronmicroscopically by labelling with ETA-gold. Double labelling experiments of lymphocytes and the use of purified T-lymphocytes revealed that the ETA-receptor was confined to T cells. Besides lymphocytes, monocytes and especially granulocytes and thrombocytes showed a significant ETA-gold labelling. The lymphocyte ETA-receptor was found to be not sensitive to trypsin and neuraminidase and was not identical with the receptors for concanavalin A, Helix pomatia-lectin and sheep erythrocytes. PMID- 3090625 TI - Immunocytochemistry--possibilities for detection of different tissue antigens and establishment of the functional role of cells. AB - The present review underlines briefly the wide distribution and application of the main immunocytochemical methods for the detection and localization of numerous antigens in tissue sections. For example, a lot of neuroactive substances have been revealed in structures of the central and peripheral nervous system by means of immunocytochemical techniques. The results obtained serve for the better understanding of the main physiological role and the interrelationships of different neuronal classes. Furthermore, some important problems accompanying an immunocytochemical staining connected with the quality of the antibodies used, with the resemblance of the chemical composition of different antigens, and with the coexistence of more neuroactive substances in a nerve cell are pointed out. PMID- 3090626 TI - [Phenoloxidase--a marker enzyme for the demonstration of cell mediated immunologic defence processes]. AB - The use of the enzyme proof for the application of cell mediated immunological defence reactions was demonstrated with preparations of pus, xenogenic transplantations, delayed hypersensitivity, and the granuloma formation. PMID- 3090627 TI - Immunohistochemical demonstration of ornithine decarboxylase in tissues. A preliminary study. AB - Using the unlabeled immunoenzyme technique, ornithine decarboxylase immunoreactivity was demonstrated in rat prostate gland and kidney. Three types of prostate epithelial cells could be revealed, displaying different strength of ODC immunoreactivity. In rat kidneys, ODC was found in proximal and distal tubules of immature tissue. Both tissues served as paradigms to optimize the immunohistochemical approach for ODC localization. PMID- 3090628 TI - Effect of several fixatives on the density of concanavalin A binding sites of murine peritoneal macrophages determined by fluorescence microscopy and X-ray microanalysis. AB - The influence of various fixatives (glutaraldehyde, formaldehyde, OsO4) on the retention of antigenicity of peritoneal macrophages was studied by means of fluorescence microscopy, scanning electron microscopy, and X-ray microanalysis. After fixation with formaldehyde the Concanavalin A (Con A) binding sites were found to be highest, whereas the fixation with OsO4 results in loss of many binding sites. The fluorescence microscopic investigations of glutaraldehyde fixed cells is impaired by fixative induced fluorescence. Therefore X-ray microanalytical determinations show better results for these cells than fluorescence microscopic measurements. On contrary to direct labelling method the number of unspecific Con A binding sites on peritoneal macrophages labelled with the sandwich method is negligible. PMID- 3090629 TI - [Lysosomal activity in prolactin cells under the effect of a dopamine agonist]. AB - The influence of bromoergocryptine, a dopamine agonist used in clinical praxis, on hormone degradation by the lysosomal system was studied in the pituitary mammotrophs of female rats. Immunocytochemistry of prolactin (protein A-gold technique) combined with the electron-microscopic visualization of the lysosomal system by its non-specific esterase activity (gold thiol-acetic acid method) revealed that bromoergocryptine administration increases the spatial extent of both the lysosomal and the hormone storage compartments with a considerable overlap and interaction between them. This change in compartmentalization may be effective in eliminating hormone excess and preserving cell integrity after release inhibition. PMID- 3090630 TI - Cytochemical and cellbiological investigations of the signal function of the erythrocyte plasmalemma--the membrane structure as code for cell life span. AB - The erythrocyte membrane was characterized with regard to its alteration of different degrees. A very important process of the membrane alteration is the expression of IgG receptor sites, which is connected with the binding of autologous IgG at the membrane. Several detection methods for membrane bound IgG were described: immunocytochemical techniques (Anti IgG--Anti Ferritin-sandwich technique, Anti IgG-Protein A-Gold- and the Silver enhancement technique), Antiglobulin agglutination test (Coombs test) and erythrocyte-macrophage test. Moreover, the topo-optical toluidine blue reaction and the ultra-histochemical NAD(H) oxidase reaction were checked to characterize the erythrocyte-macrophage interaction. Finally, the microvesiculation is understood as special form of the erythrocyte membrane disintegration, which is connected with a remodelling of an intact plasmalemma. The findings presented here summarize the fact that the membrane associated IgG regulates an immune-signal for the elimination of the erythrocytes in the Reticulo-Histiocytic-System in vivo and in vitro. Therefore, the structural integrity of the erythrocyte plasmalemma is the code for the cell life span. PMID- 3090631 TI - Ultrastructural classification of tumour cells. AB - The role of electron microscopy in the diagnosis of human tumours is described. The main purpose of employing electron microscopy in practical oncomorphology is differential histogenetic diagnosis of human tumours and identification of the level of their differentiation. It is namely this purpose that this classification is aimed at. PMID- 3090632 TI - Ischaemic changes in human myocardial cells during cardioplegia: an ultrastructural morphometric study of patients with CIHD and aortic valve vitia. AB - Ultrastructural morphometric examinations of changes in myocardial cells of two groups of patients were carried out before and after cardioplegic ischaemia. The ACB group (aorto-coronary bypass) comprised patients suffering from chronic The ACB group (aorto-coronary bypass) comprised patients suffering from chronic ischaemic heart disease, whilst the AVR group (aortic valve replacement) consisted of patients suffering from combined aortic vitium. The morphometric stereological examinations of biopsy material revealed that the ultrastructural changes in heart muscle cells were different for the two groups. This fact suggests different adaptation mechanisms of the myocardial cells of the two groups. The changes observed involved i.a. mitochondria, which in the cardiomyocytes of the ACB group diminished in size and increased in quantity, whilst in the myocardial cells of the AVR group they increased in size and diminished in number. From this it can be inferred that in the ACB group biogenesis occurred, while in the AVR group a swelling or fusion of the mitochondria took place. The results obtained indicate that the hypertrophic myocardial cells of patients with chronic aortic valve disease have a worse state of preservation after cardioplegic ischaemia and after reperfusion than those of the patients suffering from chronic ischaemic heart disease, who seem to be better able to withstand cardioplegic ischaemia and hence also surgery. PMID- 3090633 TI - Immunization against glomerular basement lamella and mesangial substance. AB - In approximately 30% of the diabetics antigens of the diabetic glomerulosclerosis were found which were not observed in controls. This finding favours the view of altered composition of glomerular extracellular substances in diabetes. PMID- 3090635 TI - [Immunohistochemical investigations on the ontogenesis of the subcommissural organ]. AB - Using an antiserum raised against bovine Reissner's fiber a ventricle border of the matrix epithel reacting in the immunohistochemical procedure according to Sternberger et al. (1970) is visible in the very early stage of the embryonic brain of Pleurodeles waltli. In the basal region of the brain the immunoreactive border later develops into the flexural organ a secretory cell formation that is situated in the deuterencephalon and spinal cord. The cells of the flexural organ release a glycoprotein into the cerebrospinal fluid, where, among other things, the Reissner's fiber is formed. Later on, Reissner's fiber is produced no longer by the flexural organ, but the subcommissural organ. It is suggested that in the very early embryonic stage the immunohistochemically reactive ventricle border, too, contains a glycoprotein that might contribute to any events in the ontogeny of the nervous system. PMID- 3090634 TI - [Morphometric and densitometric studies on the ultrastructure of endothelial cells in capillaries in tumor bearing rats]. AB - The permeability of tumor capillaries to higher molecular substances like albumin and beta-globulin is increased. The comparison of permeability is associated with a modification of the ultrastructure of the capillary wall, especially of endothelial cells and their nuclei. On micrographs of blood capillaries Zajdela Ascites-Hepatoma pregnanted rats we've studied a) morphometrically the surface and the volume of endothelial cell nuclei in relation to the time after tumor implantation, b) densitometrically the Hetero-Euchromatin-ratio in the nuclei of the same cells in relation to tumor time too. We've got the following results: The surface of the endothelial cell nuclei is increasing in the first four days, then it's decreasing to the 8th day. The volume of the same nuclei is increasing to the 4th experimental day too, then it's relatively steady. At the 6th experimental day the largest part of Heterochromatin is "euchromatinized". It will be possible to distinguish the functionally and the degeneratively nucleus' swelling with morphometrically methods. The reasons of modifications in the ultrastructure of blood capillary endothelial cell nuclei might be a) the increased demandings to the permeability of capillary wall, b) the increased activity of the MMS/RHS and c) local immunity reactions against the tumor. PMID- 3090637 TI - Glucose-6-phosphate-dehydrogenase (G6PDH) activity in the liver of golden hamsters--its dependence from estrous cycle and consequences on planning experiments. AB - Glucose-6-phosphate-dehydrogenase activity in the liver of female golden hamsters being in various stages of the estrous cycle were investigated. Animals of the pro- and diestrous stage showed a significantly higher activity than those of the met- and estrous stage. The interpretation of the results in test series has to consider this fact. Possibilities for it have been discussed. PMID- 3090636 TI - Postnatal changes in thiol: protein-disulfide oxidoreductase immunoreactivity of rat brain. AB - Thiol: Protein-disulfide oxidoreductase (TPO) was localized in the brain of juvenile and adult rats by use of the unlabeled immunoperoxidase technique. In the brain of adult animals, TPO protein was revealed in neurons of Nucc. supraopticus and paraventricularis as well as in the subcommissural organ. In the developing rat, TPO seems to be a constituent of almost all neurons. The roles played by the enzyme remain to be elucidated, however. PMID- 3090638 TI - Electron microscopic visualization of the capsule of Pasteurella multocida. AB - The results of electron microscopic visualization of capsules of Pasteurella multocida by means of negative staining and section methods are described. Using ruthenium red or a complex of platinum in negative staining, relatively homogeneous capsules were visualized, using alcian-blue, coarse-fibrous structured capsules appeared. The incubation with antiserum partially revealed narrow capsule zones in the sections. Ferritin-linked IgG labelled amorphous material between the bacteria or floccular appendages on the bacterial surface. Gold-linked Con A deposited on thick cord structures, on loose material between the bacteria and sometimes on their cell wall. PMID- 3090639 TI - [Atomic absorption spectrophotometric determination of zinc in granulocytes, lymphocytes and serum of untreated and alloxan diabetic rats]. AB - Atomic absorptions spectrophotometric determinations of zinc in serum, granulocytes and lymphocytes after separation of blood samples of normal and alloxan diabetic rats, control persons and diabetics by the method of Boyum verify our conception that changes of metal content and structure in cells by metal chelating agents are induced primary by chemical and secondary by disturbed carbohydrate metabolism conditions. Alloxan (200 mg/kg of body weight, intraperitoneally) destroys selectively not only the B-cells of the islets of Langerhans but also the granulocytes, while the lymphocytes are not changed in respect to the zinc content and cell count. The lymphocytes of diabetics are unchanged in the zinc content, too. The earlier opinion that leucocytes belong to the slowly exchanging zinc compartments of the blood is only exact for lymphocytes, whereas the granulocytes and the serum, corresponding to an exchange pool of metal ions, may play a more important role in the transport system of the zinc. PMID- 3090640 TI - Antigen spot test for the detection of specific antibodies in the nanogram range by means of the PAP-technique. AB - A modification of a method is described for detection of antigens and antibodies by means of nitrocellulose paper discs as high-capacity solid phase antigen carrier and mouse PAP. Mouse IgG spotted on nitrocellulose paper may be easily detected at a level of 1 ng. Detection of specific antibodies is possible down to a concentration of 80 ng per ml. This method is of practical importance for the screening of hybridoma supernatants. PMID- 3090641 TI - Critical point drying by use of distilled CO2. AB - For avoiding specimen contamination with particles or liquid residues from CO2 supply cylinders during critical point drying the carbon dioxide is taken from the gaseous phase. Condensation takes place in the water cooled pipe between supply cylinder and CPD-apparatus. A sufficient flow of liquid CO2 is guaranteed, all solid and nonvolatile liquid contaminations are eliminated. PMID- 3090642 TI - Topo-optical investigation of the erythrocyte membrane alteration after prolonged retention in the splenal reticulum. AB - The extent of the splenal transit time is an important factor which influences the immunological behaviour of the red blood cells. An increased transit time of the RBC in the splenal reticulum leads to conformational effects on the erythrocyte glycocalyx. They consist in spatial disorder of the oligosaccharide side chains of the glycophorins with their sialic acid residues. These spatial disorders of the sialic acid residues correspond with the expression of IgG receptors, which initiate the process of the secondary elimination of the red cells. PMID- 3090643 TI - Immunocytochemical investigations of the membrane of experimentally altered and physiologically aged erythrocytes. AB - The expression of IgG receptor sites during aging of red blood cells plays an important role in the elimination process of these cells by the Reticulo Histiocytic System. By means of an indirect protein A gold-method, membrane bound IgG was detected immunocytochemically on pronase and neuraminidase treated red blood cells as well as on physiologically aged red cells. The silver enhancement of the gold particles led to an improved labeling of the bound IgG favouring its quantification at both electron and light microscopic level. The result of this gold-silver-technique was analyzed semiquantitatively at the light microscopic level by use of a Vickers scanning microdensitometer. It was shown that the aging of erythrocytes as well as the enzymatic alteration of the erythrocyte glycocalyx by pronase and neuraminidase are accompanied with an unmasking of IgG receptor sites followed by an IgG loading of the cells in presence of autologous serum or plasma. The experimental results, which are presented here indicate that a silver enhancement of gold particles is sufficient to signalize changes in membrane bound ligands at low concentrations. PMID- 3090644 TI - Factors regulating microtubule structure--a minireview. AB - The pathway of tubulin assembly is controlled by a lot of effectors. We summarize some of these effectors favouring the formation of microtubules or inducing several MT-aberrant, polymorphic structures. Both in vivo and in vitro, microtubules with different protofilament numbers were found. In vivo, microtubules are composed of 11-16 protofilaments. The protofilament number of microtubules formed in vitro varies from 8-17. We describe some effectors responsible for the diversity of the protofilament number in microtubules. Moreover, differences in the amino acid sequences of distinct tubulins should be taken into account, too. The protofilament number of an established microtubule can be still altered if activities of effectors or microenvironmental conditions are changed. Thus, the protofilament number of microtubules is a dynamic property based on the permanent tubulin exchange. PMID- 3090645 TI - [Characterization of lectin receptors on cell surfaces with regard to functional aspects]. AB - The actual definitions of lectins are presented and discussed and lectins are classified as one group of the affinitins. The ability of lectins to bind carbohydrates serves as a widely used principle in the nature for cell recognition and adhesion processes. By means of labelled glycoconjugates the identification, localization and quantitation of receptor bound lectins can be investigated as by lectinological as by a combination of lectinological and immunological reactions. The special properties of toxic lectins are discussed by use of the lectin I from mistletoe as characteristic example. The coupling of A chains with antibodies (immunotoxins) or other haptomers (affinotoxins) leads to agents render it possible to influence directly cell functions. PMID- 3090646 TI - Immunochemical and immunohistochemical studies on non-muscle contractile systems. PMID- 3090647 TI - [Structure of the erythrocyte membrane]. AB - A short survey is given about the components and the structure of the human erythrocyte membrane. The dominating transmembrane proteins, the anion exchange protein as a main constituent of the intramembranous particles and as an anchoring site of the membrane skeleton, and the glycophorin A as the main component of the glycocalyx are discussed in particular. The structure of the membrane skeleton, its binding sites at the inner membrane aspect as well as the nature of the junctions of that network and the functions of the membrane skeleton are spoken about. PMID- 3090648 TI - [Abdominal typhus and paratyphoid fevers--1984]. PMID- 3090649 TI - [Prevention of post-traumatic epilepsy]. PMID- 3090650 TI - 5-Fluorouracil and mitomycin C in advanced breast cancer. AB - Fifty-seven patients with advanced breast cancer were treated with a combination of 5-fluorouracil and mitomycin C (FuMi). Fifty-three were previously treated with hormones and/or cytotoxic drugs. Complete and partial remissions (CR, PR) were seen in 16%, stationary disease in 46%, and progressive disease in 38%. The mean time to remission was 4.5 (CR) to 4.0 (PR) months. The toxicity was mild and consisted mainly of thrombocytopenia. The FuMi-regimen may be a useful alternative in advanced breast cancer, at least in progression after previous systemic therapy, and if a moderate toxicity is considered important. PMID- 3090651 TI - [Analysis of amyloidosis in myeloma. Clinical, biological and prognostic study]. PMID- 3090652 TI - [Decreased penicillin sensitivity in strains causing disseminated gonococcal infection]. PMID- 3090654 TI - [Parenteral nutrition of the surgical patient]. PMID- 3090655 TI - [Response of prolactin (PRL) to the administration of TRH in male patients with alcoholic cirrhosis: 2. Relation of PRL to diuresis and urine excretion of electrolytes]. PMID- 3090653 TI - [Importance of parenteral nutrition in cardiac surgery]. PMID- 3090656 TI - [Duodenal diverticuli: therapeutic criteria (our experience in 60 cases)]. PMID- 3090657 TI - The onset of female puberty: studies in the rat. PMID- 3090658 TI - Interactions of catecholamines and GnRH in regulation of gonadotropin secretion in teleost fish. PMID- 3090659 TI - Evolutionary aspects of the endocrine and nervous systems. PMID- 3090661 TI - Requirements and results of liver perfusion. PMID- 3090662 TI - Mechanism of the protective activity of ICRF-187 against alloxan-induced diabetes in mice. AB - ICRF-187, (+)-1,2-bis(3,5-dioxopiperazine-1-yl)propane, has been shown to protect against alloxan diabetes (el-Hage et al., 1981). Since alloxan-induced pancreatic beta cell damage is thought to be mediated through the generation of highly reactive oxygen radicals by a metal catalyzed reaction involving both superoxide anion and hydrogen peroxide, in the present study the protective activity of ICRF 187 was compared with that of free radical scavengers, microsomal enzyme inhibitors and chelating agents. The free radical scavengers DMSO, vitamin E and WR2721 markedly reduced alloxan-induced hyperglycemia. ICRF-187 was found not to interact with superoxide anions, and there is no evidence to indicate that any of the known biological effects of ICRF-187 are mediated through free radical scavenging activity. SKF-525 and cimetidine, known inhibitors of drug metabolizing enzymes, also protected against the diabetogenic action of alloxan. Since it was found that ICRF-187 did not alter hexobarbital sleeping time, this compound must protect by a mechanism other than microsomal enzyme inhibition. Since the chelating agents EDTA and DETAPAC were found to protect against alloxan diabetes, ICRF-187 or its hydrolytic products, which are structurally similar to EDTA, could function as chelating agents. Transitional metals such as iron, zinc and copper were found to bind preferentially to a hydrolysis product of ICRF-187. Chelation of iron by ICRF-187 or its hydrolytic products could decrease in vivo formation of reactive oxygen radicals and provide a means for protecting against chronic anthracycline cardiotoxicity and alloxan diabetes. PMID- 3090663 TI - Attempts to modify changes in the piglet small intestine after weaning. AB - The possible causes of changes in the piglet small intestine after weaning were investigated. Groups of piglets weaned at three weeks old were either given oral oxytetracycline daily, weaned on to a regularly fed sow-milk replacer or weaned on to specially formulated diets based on casein or hydrolysed casein as the protein source. After five days, changes in small intestinal structure and brush border enzyme activities were compared with previous findings in weaned and unweaned animals of the same age. The presence of enterotoxigenic Escherichia coli and rota-viruses in the intestines and the occurrence of diarrhoea were also noted. Consumption of the diet based on hydrolysed casein resulted in significant modifications to crypt depth and brush border enzyme activity at sites between 50 and 75 per cent along the length of the small intestine. Possible reasons for this protective effect, which include the low level of antigenicity of the diet, are discussed in relation to normal intestinal changes after weaning. PMID- 3090660 TI - Physiological and clinical studies of GRF and GH. PMID- 3090664 TI - Transport abnormalities from single-breath dynamics of Ar, CO2 and O2. AB - A model framework is developed for analyzing non-invasive measurements of Ar, CO2, O2, and lung volume during a single exhalation from healthy and diseased lungs. The objective is to distinguish ventilation inhomogeneity from gas exchange limitations associated with alveolar-capillary transport and processes within the blood. Several practical, quantitative indices are compared to provide distinction and physiological interpretation in terms of rate-determining transport processes. Some indices arise from a model in which the composition in the alveolar space differs from that of the exhaled gas. Other indices are computed from the effective dead-space volumes for Ar, CO2, and O2. Ventilation inhomogeneity is accounted for by the Ar dynamics. Values of these indices were computed from experiments with human subjects having normal lungs, restrictive pulmonary disease, or chronic obstructive pulmonary disease. These three groups are clearly distinguished by a pair of indices: one reflects ventilation inhomogeneity, while the other reflects dysfunction associated with the alveolar capillary transport and capillary blood flow and distribution. PMID- 3090665 TI - Effects of chronic administration of phenobarbital in low doses on control of breathing in the cat. AB - The ventilatory response to CO hypoxia (FICO = 0.0025), hypercapnia, and hypoxia was studied in a group of intact, conscious cats before and during chronic administration of phenobarbital (60 mg/day). It was found that the ventilatory response to hypercapnia or hypoxia was not significantly modified during phenobarbital administration. However, the ventilatory response to CO hypoxia was markedly blunted with phenobarbital: the initial ventilatory inhibition was still observed but the subsequent hyperventilation was delayed. Furthermore, the tachypnea was less intense and the decrease in tidal volume was smaller during CO hypoxia. In addition, the behavioral reactions which usually accompanied the tachypnea were attenuated and unconsciousness was often noted. These results indicate that the modifications caused by phenobarbital do not result from a general inhibition of the respiratory control network but rather from a selective inhibition of the structures rostral to the brain stem. As a consequence, the behavioral reactions and resulting respiratory activation were attenuated. Since the hypoxic tachypnea and behavioral reactions are observed only during central hypoxemia, it is concluded that arterial chemoreceptor afferents normally inhibit the supra-pontine structures which are otherwise stimulated by central hypoxemia. PMID- 3090666 TI - Ventilatory recovery from hypothermia in anesthetized cats. AB - Ventilation and breathing pattern were recorded in a group of seven anesthetized cats during rewarming from 24 to 38 degrees C of esophageal temperature. It was found that at 24 degrees C, ventilation was very much depressed accounting for an alveolar hypoventilation resulting in hypoxia and hypercapnia. During rewarming, ventilation increased steadily; this was caused by sequential changes in central inspiratory activity (VT/Ti) and Ti/Tt ratio reflecting breath timing. Changes in VT/Ti have been initially attributed to an improvement in chemoresponsiveness and subsequently, to an involvement of supra-pontine thermoregulatory control areas during rewarming. Marked changes in breath timing, especially observed between 28 and 34 degrees C, have been attributed to a direct effect of rewarming upon the brain stem respiratory network. It has the result, that during hypothermia, several components of the respiratory control system are differently affected causing marked changes in breathing pattern and ventilation. They are accompanied by modifications in arterial blood pressure and heart rate. PMID- 3090667 TI - [Treatment of post-portosystemic shunt chylous ascites with total parenteral nutrition]. PMID- 3090668 TI - Ovulation, follicular growth and ovarian reactivity to exogenous gonadotropins in adult rats with unilateral or bilateral section of the vagi nerves. PMID- 3090670 TI - [Ankle fractures and osteosynthesis. Functional evaluation and rehabilitation]. PMID- 3090669 TI - [Acute trypanosomiasis. Report of a case and review]. PMID- 3090671 TI - [Significant increase in the number of allo-immunizations detected during pregnancy in 1984]. PMID- 3090672 TI - [Hyperammonemia during sodium valproate therapy: clinically relevant or accidental finding?]. PMID- 3090673 TI - [Albumin as a prognostic index in the critical surgical patient]. PMID- 3090675 TI - [Effect of combinations of aminoglycosides with betalactamine on Pseudomonas aeruginosa strains in vitro]. PMID- 3090674 TI - [Cholecystectomy and biliary surgery in the aged]. PMID- 3090677 TI - Serum beta 2-microglobulin levels in multiple myeloma and monoclonal gammapathy of undetermined significance: a clinical study of 55 patients. AB - Previous reports provided clear evidence that serum beta 2-microglobulin (beta 2m) is a marker highly correlated with the total mass of myeloma cells and suggested its use in the follow-up of patients with plasma cell tumors. Serum beta 2m levels were measured in 38 patients with multiple myeloma (MM), in 17 patients with monoclonal gammapathy of undetermined significance (MGUS) and in 32 normal control subjects. While statistically significant differences could be established between controls and both MM and MGUS patients, between patients with MM at stage III and patients with MM at lower stages as well as between patients with MGUS and patients with mostly advanced MM, it was not possible to statistically separate patients with MM at stage I from patients with MM at stage II, patients with untreated MM from patients with treated MM and, finally, patients with MGUS from patients with low cell mass MM. These results substantially confirm the already published data and lead to the conclusion that serum beta 2m determination is a useful test in the clinical management of monoclonal gammapathies, but it does not allow a differential diagnosis between benign and malignant forms of the disease. PMID- 3090676 TI - [Is a manifestation of diphtheria possible in persons with a protective antibody titer?]. PMID- 3090678 TI - [Pseudotumoral osteolysis caused by diphosphonates]. PMID- 3090680 TI - A new form of coagulation factor VII in plasma. AB - We have reported the existence of a novel form of coagulation factor VII - probably a factor VII-phospholipid complex - in plasma from pregnant women and men at risk for cardiovascular disease. We report here further observations on the presence and characteristics of this complex. Some apparently healthy individuals who, on testing by standard methods, have normal levels of factor VII activity achieve such levels by means of a phospholipase C-sensitive modification of (some of) their factor VII molecules. Their residual factor VII activity after phospholipase C treatment of plasma may be as low as 10-20 U/ml. Antiserum to the protein component of thromboplastin (apoprotein III) had no effect on the factor VII activity, whereas antiserum to factor VII effectively blocked both the total factor VII activity and the residual activity of factor VII after treatment of plasma with phospholipase C. These factor VII complexes precipitate with the VLDL/LDL fraction in lipoprotein precipitations. PMID- 3090679 TI - Effect of short-term lithium carbonate administration in hyperthyroidism, with or without associated ophthalmopathy. AB - The study was carried out on 21 female hyperthyroid patients aged 22-53 years, with or without associated ophthalmopathy, admitted to the Endocrinology ward of the 1st Medical Clinic of the Craiova County Hospital, Romania, between 1983 and 1985. Administration of lithium carbonate was proceeded and followed by radioimmunoassay (RIA) determinations of T3 and T4 and measurement of Achilles' reflex (AR). Two regimens were employed. The first comprised ten patients receiving doses of 500 mg/day lithium carbonate and the second 11 patients who had an associated ophthalmopathy and who received 250 mg/day lithium carbonate and 30 mg/day carbimazole. Lithium administration was discontinued after 4 weeks. The results of the therapy suggest a possible intervention of lithium carbonate in the process of blocking the biosynthesis of thyroid hormones and/or its regulating processes, with concomitant improvement of the clinical status, much more in the patients without ophthalmopathy. PMID- 3090682 TI - [Human pancreatic growth hormone-releasing factor]. PMID- 3090681 TI - Prothrombin Segovia: a new congenital abnormality of prothrombin. AB - A family with a new congenital dysprothrombinemia is presented. The propositus is a 21-yr-old man who presented simultaneously with hemartrosis of the left knee and an extensive hematoma following a minor trauma. Prothrombin time and activated partial thromboplastin time were prolonged. Prothrombin activity was very low when measured by biological assay using physiological activators (7% by one-stage method and 20% by two-stage method) or a Russel's viper venom-cephalin mixture (23%), Notechis scutatus scutatus venom (15%) and Echis carinatus venom (17%); in contrast, the level was found to be borderline to normal using Taipan viper venom (64%) and normal by both staphylocoagulase and immunologic methods. Family studies revealed consanguinity between the propositus' mother and father and both presented a 50% reduced prothrombin level when physiological activators or Echis carinatus viper venom were used. A line of identity between normal and abnormal prothrombin was observed on immunodiffusion. The migration of the abnormal prothrombin was less anodic and was not changed by the addition of calcium. The patient's serum showed 3 bands in the bidimensional immunoelectrophoresis system, whereas normal serum showed only 2 bands. The term prothrombin Segovia is proposed to define this new prothrombin abnormality. PMID- 3090683 TI - New fossil upsets human family. PMID- 3090685 TI - Upstream operators enhance repression of the lac promoter. AB - To study regulation of transcription by distant elements, a wild-type lac operator was inserted upstream of a promoter-constitutive operator control region. The upstream operator is shown to aid in repression of transcription from the mutant control region. The effectiveness of the upstream operator as a function of its distance from the mutant control region parallels the length dependence observed for DNA cyclization. A quantitative model is proposed for action-at-a-distance of DNA control sites in which protein-protein and protein DNA interactions are mediated by DNA looping. In this model, the effective concentrations of interacting proteins that are tethered by DNA are determined by the length of the intervening DNA and by its inherent bending and torsional stiffness. This model makes a number of predictions for both eukaryotic and prokaryotic control sequences located far from their sites of action. PMID- 3090684 TI - The predicted structure of immunoglobulin D1.3 and its comparison with the crystal structure. AB - Predictions of the structures of the antigen-binding domains of an antibody, recorded before its experimental structure determination and tested subsequently, were based on comparative analysis of known antibody structures or on conformational energy calculations. The framework, the relative positions of the hypervariable regions, and the folds of four of the hypervariable loops were predicted correctly. This portion includes all residues in contact with the antigen, in this case hen egg white lysozyme, implying that the main chain conformation of the antibody combining site does not change upon ligation. The conformations of three residues in each of the other two hypervariable loops are different in the predicted models and the experimental structure. PMID- 3090686 TI - A physiological role of epidermal growth factor in male reproductive function. AB - Epidermal growth factor (EGF) stimulates the proliferation of various mammalian cells in culture, but its physiological role is not well defined. In mature male mice, large amounts of EGF are produced in the submandibular gland; it is present in the circulation at approximately 5 nanograms of EGF per milliliter of plasma. Sialoadenectomy (removal of the submandibular glands) decreased the amount of circulating EGF to an undetectable level but did not affect the circulating levels of testosterone or follicle-stimulating hormone. The number of mature sperm in the epididymis decreased by as much as 55 percent; the number of spermatids in the testis decreased by 40 to 50 percent; and the number of spermatocytes increased by about 20 percent. Administration of EGF to sialoadenectomized mice restored both the sperm content of the epididymis and the number of spermatids in the testis to normal. Thus, EGF may play a role in male reproductive function by stimulating the meiotic phase of spermatogenesis. PMID- 3090687 TI - Induction of membrane ruffling and fluid-phase pinocytosis in quiescent fibroblasts by ras proteins. AB - Expression of the ras oncogene is thought to be one of the contributing events in the initiation of certain types of human cancer. To determine the cellular activities that are directly triggered by ras proteins, the early consequences of microinjection of the human H-ras proteins into quiescent rat embryo fibroblasts were investigated. Within 30 minutes to 1 hour after injection, cells show a marked increase in surface ruffles and fluid-phase pinocytosis. The rapid enhancement of membrane ruffling and pinocytosis is induced by both the proto oncogenic and the oncogenic forms of the H-ras protein. The effects produced by the oncogenic protein persist for more than 15 hours after injection, whereas the effects of the proto-oncogenic protein are short-lived, being restricted to a 3 hour interval after injection. The stimulatory effect of the ras oncogene protein on ruffling and pinocytosis is dependent on the amount of injected protein and is accompanied by an apparent stimulation of phospholipase A2 activity. These rapid changes in cell membrane activities induced by ras proteins may represent primary events in the mechanism of action of ras proteins. PMID- 3090688 TI - Genetic evidence for transmembrane acetylation by lysosomes. AB - Acetyl-CoA:alpha-glucosaminide N-acetyltransferase is a lysosomal-membrane enzyme deficient in a genetic disorder, Sanfilippo disease type C. The enzyme catalyzes the transfer of an acetyl group from cytoplasmic acetyl-coenzyme A (acetyl-CoA) to terminal alpha-glucosamine residues of heparan sulfate within the organelle. Previous kinetic experiments indicated that the enzyme carries out a transmembrane acetylation via a ping-pong mechanism; the reaction can therefore be dissected into two half reactions--acetylation of the enzyme, and transfer of the acetyl group to glucosamine. Cells derived from patients were found to differ in their ability to perform each half reaction. Five cell lines (derived from three families) were able to catalyze acetylation of the lysosomal membrane and to carry out acetyl-CoA/CoA exchange, whereas a sixth cell line was devoid of this activity. PMID- 3090690 TI - [Human rights in nursing. Health personnel and human rights]. PMID- 3090689 TI - Therapy of epidemic Kaposi's sarcoma. AB - Epidemic Kaposi's sarcoma, a neoplasm associated with AIDS, is rapidly becoming common in the United States and Europe. The pathogenesis of this form of Kaposi's sarcoma has not yet been fully understood, but epidemiological clues point to the possibility that an infectious agent (in addition to the AIDS virus HTLV-III) or an environmental toxin may be involved. The natural history and clinical course of epidemic Kaposi's sarcoma is variable. The life expectancy of an AIDS patient with Kaposi's sarcoma is probably related to his underlying immunologic status as evidenced by propensity to develop life-threatening opportunistic infections. Patients with this neoplasm should be entered on experimental treatment programs when possible in order to improve our knowledge about rational management of this disease. Recombinant interferon alfa-2a, single agent chemotherapy, and radiation all have roles in the management of the disease. PMID- 3090691 TI - [The cardinal symptom. Difficulties in concentration of schoolchildren]. PMID- 3090693 TI - [Juvenile arthritis]. PMID- 3090692 TI - [BCG in question]. PMID- 3090695 TI - [Vitamin A protects the eyesight]. PMID- 3090694 TI - [Saying goodbye]. PMID- 3090696 TI - [Eggs]. PMID- 3090697 TI - [Iatrogenic diseases: an epidemic in our times]. PMID- 3090699 TI - [Nursing actions for patients on continuous arteriovenous hemofiltration]. PMID- 3090698 TI - [Bladder catheterization...again]. PMID- 3090700 TI - [Directives and decisions in the environmental area]. PMID- 3090701 TI - [Hypertension in pregnancy. Prenatal detection and treatment]. PMID- 3090702 TI - [AIDS (acquired immunodeficiency syndrome)]. PMID- 3090703 TI - [Cell proliferation in the carcinogenetic processes of tongue carcinoma induced by 4-nitroquinoline-1-oxide in rats. 1. Relation between morphology and microvascular architecture of the filiform papillae of dorsal surface of the tongue in normal albino rats]. PMID- 3090704 TI - Skeletal surveys in multiple myeloma. Radiologic-clinical correlation. AB - Thirty-three patients with multiple myeloma were studied with serial skeletal surveys, serum immunoglobulin levels, and postabsorptive urinary hydroxyproline (Spot-HYPRO) determinations. Twenty receiving chemotherapy were also followed with skeletal surveys in order to evaluate bone response to treatment. A close association was found between skeletal findings and changes in immunoglobulin levels with positive correlation in 71% of the patients. A similar association was found between skeletal disease and Spot-HYPRO level changes in 65%. Five of 12 patients (42%) with partial or complete clinical response to chemotherapy, demonstrated improvement in the appearance of skeletal lesions. Positive correlation between the roentgenographic changes and clinical markers of myeloma as well as therapeutic response, indicates that skeletal surveys are useful and effective in monitoring patients with multiple myeloma. PMID- 3090705 TI - The role of bone scintigraphy in osteogenic sarcoma. AB - Hospital records of 27 children with osteogenic sarcoma were reviewed in an effort to define the usefulness of skeletal scintigraphy in the initial evaluation and follow-up of their disease. Serial bone scans as well as plain radiographs, linear tomograms, and computed tomograms were evaluated for evidence of bone or lung metastases. Eighteen patients developed lung metastases and three developed bone metastases. Seven patients demonstrated uptake of tracer in lung metastases, however, the lesions were all easily identifiable by radiographic means. All bone metastases were detected by scintigraphy, in one instance prior to radiographic abnormality. In no cases were bone metastases known to occur in the absence of lung metastases. None of the bone scans performed for routine follow-up purposes resulted in altered therapy for the patient. We propose that skeletal scintigraphy is useful in the initial metastatic work up of osteogenic sarcoma, and may be helpful in some patients with specific indications during their follow-up, but is less valuable when there is no clinical suspicion for bone metastases. PMID- 3090707 TI - Health status and medical expenditures: is there a link? AB - Until now, cross-national studies have not demonstrated a positive relationship between health care expenditures and improved health status, as measured by such indicators as age-adjusted mortality rates. It has therefore been argued that cutting expenditures will not have a negative effect upon health status. Using health and life-style data from the OECD for Germany, the United Kingdom, The Netherlands, France, Sweden and the United States, this study finds that when one holds constant those changes in life style that have an impact upon health (e.g. smoking, drinking, traffic accidents, dangers on the job) and adjusts for inflation and population size, health care expenditures do bear a positive relationship to health status. This suggests that reductions in health care expenditures may well have some cost in terms of overall health. PMID- 3090708 TI - The geography of health in South-East Mexico: a research study and agenda. AB - Work on the geography of health has been undertaken in association with the Centro de Investigaciones Ecologicas del Sureste, Chiapas State, Mexico. An example is given from a study of relationships between housing and Chagas' disease in the village of Agua Azul in Chiapas. Prospects for future work in medical geography might involve further studies of Chagas' disease and onchocerciasis, and of the health of refugees and of populations involved in the exploitation of petroleum reserves. PMID- 3090706 TI - International comparison of drug consumption: impact of prices. AB - Cross-national comparisons in drug consumptions are usually made in terms of dollars spent annually per person on pharmaceuticals. Expenditure reflects consumption, however, if measured in the same or very similar prices. When drug prices in different countries vary significantly, the expenditure comparisons may create a false image of consumption. A comparative work has been undertaken covering six countries: France, Great Britain, Federal Republic of Germany, Italy, Switzerland and the United States of America. It appears that consumption of medicines has reached the highest level in France and Italy, while the highest spending occurs in Switzerland and the F.R.G. PMID- 3090710 TI - The bottom line: where the black ink meets the red. PMID- 3090709 TI - Caution on cordless telephones. PMID- 3090711 TI - Diffuse interstitial lung disease in neurofibromatosis. AB - An association of neurofibromatosis with diffuse interstitial lung disease is thought to exist, though there have been relatively few large studies of it. The pulmonary manifestations consist of diffuse interstitial fibrosis or formation of bullae, or a combination of both. Our experience with this disease process during a ten-year period shows slightly less than a 7% incidence of diffuse interstitial lung disease in our patients with neurofibromatosis. We include a case of neurofibromatosis and diffuse lung disease that is somewhat unusual in the formation of bullae in the lower lobe, in contradistinction to its marked upper lobe predominance. PMID- 3090712 TI - Two to three days treatment of typhoid fever with ceftriaxone. AB - Pharmacokinetic properties of ceftriaxone, such as sustained tissue drug levels over 24 hours after a single injection; good penetration of the antibiotic into cells; significant biliary excretion as active unchanged compound and high potency against S. typhi, should make it possible to significantly shorten the treatment of typhoid fever. To test this hypothesis a pilot, open study was initiated. 17 adult patients suffering from uncomplicated typhoid or paratyphoid fever, documented by blood culture, were treated with 4g ceftriaxone once daily for three days (4 patients) or two days (15 patients). The cure rate of 17 assessable patients was 94.2% (one failure). One possible relapse was observed two months after treatment. It is to be noted that no patient in the study suffered from a severe form of the disease. PMID- 3090713 TI - Studies on Echinostoma ilocanum in the Philippines. AB - Echinostoma ilocanum is widespread among the Philippine Islands but only 3% of over 30,000 stools were found to be positive for eggs. The prevalence rates were highest in Ilocana populations of northern Luzon; 11% of over 7,000 stools examined, however, rates as high as 44% were found. Pila luzonica is eaten uncooked by some people and metacercariae from these snails developed into adults in a number of laboratory animals. Rats, mice and hamsters were the most susceptible with patent infections developing as early as 7 days and lasting for 328 days. There seems to be little disease in humans and animals infected with this parasite. PMID- 3090714 TI - An attempt to study the case fatality rate in Schistosoma japonicum infection in the Philippines. AB - As a sequence to a cross-sectional study on the clinical gradient of the disease by Pesigan et al., (1965) a follow-up of the subjects in that study was made after 12 years. Of the 135 untreated cases followed up, 23 (17.04%) died from various causes of which 12 (8.89%) had signs and symptoms attributable to schistosomiasis as the immediate cause or one of the main causes of death. This occurred in 1 to 11 years with an average of 5 years, which corresponds roughly to 1.78% of the infected cases per year. This is considered a conservative estimate because in the other deaths due to other diseases, schistosomiasis is a contributory cause. A diminishing severity of the disease was observed among the surviving patients which could imply that they must have developed some degree of immunity to the disease. PMID- 3090715 TI - [Traumatic extraperitoneal perforation of a duodenal diverticulum]. PMID- 3090716 TI - Endocrine studies in patients with isolated gonadotrophin-releasing hormone deficiency. AB - Twelve black women with isolated gonadotrophin deficiency were studied. After administration of intravenous gonadotrophin-releasing hormone (GnRH), all patients had subnormal gonadotrophin responses. However, after priming with subcutaneous GnRH (in 9 patients) follicle-stimulating hormone responses improved in 4 patients and luteinizing hormone responses in 7 patients. Prolactin responses to intravenous thyrotrophin-releasing hormone were significantly decreased at 20 and 60 minutes, when compared with reference subjects (P less than 0.01). In response to insulin-induced hypoglycaemia, prolactin responses were heterogeneous in 11 patients, while those of growth hormone were suboptimal in 8 of the 11 patients tested. PMID- 3090717 TI - An analysis of computed tomographic brain scans. A computer-based study. AB - A microcomputer was used to analyse prospectively 1,000 sequential computed tomographic (CT) brain scans to assess whether the scanner was being used in a cost-effective and efficient manner. Of the patients scanned 58% had cerebral lesions. All the usual indications for CT examination were shown to be worth while, the exception being psychiatric cases. PMID- 3090718 TI - [Tumor calcinosis in a hemodialysis patient. Trial of surgical and drug treatment]. PMID- 3090719 TI - [A case of caliceal diverticulum]. PMID- 3090720 TI - [Streptococcus faecalis in urinary tract infections]. PMID- 3090721 TI - [Qualitative comparison of different irradiation technics]. AB - A factor is defined which allows a quantitative comparison of different irradiation schemes. In this factor, the spatial as well as chronological dose distribution is taken into consideration, further it contains the varying radiosensitivity of the additionally exposed tissues. So the comparison of the radiobiologic effectiveness of different irradiation schemes based on this factor is more instructive than a simple comparison of the total dose. The study is continued by an analysis of the possible sources of error influencing the quality of a radiotherapy. PMID- 3090722 TI - [Electron irradiation of cervix cancer using a new transvaginal tube system attached to the betatron]. AB - A new tube system for the betatron, which normally is only applied in percutaneous electron therapy, was developed at the Radiotherapeutic Department of the Medical Faculty of Istanbul. The new system allows to use the betatron also in transvaginal irradiation of the uterine cervix cancer. The authors describe the technical features of this system, its clinical application, and the results achieved. In great tumor centres where every type of malignant disease is treated, it is indispensable to dispose of the equipment necessary for certain very special cases, even if this equipment is not used frequently. In recent years, applicators for cavitary therapy and high voltage units for percutaneous therapy have been gradually substituted for the tube system employed in former times with orthovolt therapy units in intravaginal irradiation of cervical and vaginal carcinomas. There are cases, however, where the therapy techniques used nowadays are not sufficient or where a cavitary therapy should be used. Furthermore electrons which today can easily be produced for percutaneous surface therapy with linear accelerators can also be used for transvaginal therapy. We, too, have developed a new tube system which was attached to the betatron and used in intravaginal irradiation. This study describes the tube system, its clinical application, and the results achieved. PMID- 3090723 TI - Positive nitrogen balance with human growth hormone and hypocaloric intravenous feeding. AB - Nitrogen equilibrium cannot be achieved in surgical patients without adequate nitrogen and calorie intake, frequently requiring central venous feedings. To investigate the hormonal environment under which nitrogen retention might be achieved during hypocaloric feedings, we administered peripheral vein nutrition with growth hormone (GH) to four healthy male patients. The intravenous diets provided 50% of estimated energy requirements (mean 566 kcal/m2/day) and adequate nitrogen (6 gm/m2/day). Each subject was studied for two 7-day periods; 10 mg of GH was given daily during one period and placebo during the other. Administration of GH decreased weight loss, caused retention of nitrogen, potassium, and phosphorus in amounts closely matching their proportions in skeletal muscle, and stimulated insulin production. GH also raised serum levels of free fatty acids and glycerol, increased urinary excretion of ketones, and favored fat oxidation in the postabsorptive state. Hyperinsulinemia and increased lipolysis and ketogenesis may augment the primary effects of GH. Further studies at adequate and approximately 30% of adequate calorie intake confirmed these findings. Maintenance of body protein with GH may allow improved nutritional care of catabolic patients that was previously unrecognized. PMID- 3090724 TI - Transplantation of cultured pancreatic islets to BB rats. AB - Pancreatic islets held in tissue culture before transplantation into artificially induced diabetics are not rejected. In animals and human identical twin transplants, the autoimmunity of naturally occurring diabetes may destroy islets, even if rejection is avoided. Therefore we studied whether autoimmune damage of islets can be avoided by pretransplant culture. Recipients were BB rats, which spontaneously developed diabetes. Donors were either Wistar Furth (WF) (major histocompatibility [MHC] identical to BB rats) or Lewis (MHC nonidentical to BB rats). Islets were inoculated into the portal vein either immediately after isolation or after 14 days in tissue culture (95% air, 5% CO2, 24 degrees C). Recipients of cultured islets received a single injection of 1 ml of antilymphocyte serum at the time of transplant. Recurrence of diabetes after transplantation of freshly isolated MHC incompatible Lewis islets occurred rapidly on the basis of rejection or autoimmune damage (or both). Precultured Lewis islets had prolonged or permanent survival. Freshly isolated MHC compatible WF islets were destroyed, and no improvement was seen with culture. We conclude that autoimmune destruction of transplanted islets can be avoided by tissue culture, as can rejection. This is important because this strategy is effective only if recipient and donor differ at the MHC locus. Islet donors may need to be selected on the basis of disparity of histocompatibility factors. PMID- 3090725 TI - Continuous arteriovenous hemofiltration: improved survival in surgical acute renal failure? AB - Continuous arteriovenous hemofiltration (CAVH) is an effective method for renal failure management that has the potential to decrease mortality rates. This hypothesis has not been comparatively studied. Fifty six patients with acute oliguric renal failure complicating multiple organ failure had measurements of resting energy expenditure by indirect calorimetry, caloric and protein intake, energy balance, and outcome. Two management protocols included hemodialysis, full calories, and low protein (phase I) or CAVH, full calories, and high protein (phase II). The survival rate in phase I was 12% and 28% in phase II (not a statistically significant difference); CAVH did facilitate parenteral feeding. Patients with positive energy balance had improved survival compared with those with significant energy deficit (37.5% versus 9.4%, p less than 0.025). We conclude that full nutritional support improves survival in acute renal failure. The method of renal replacement therapy is of secondary importance, but CAVH has distinct advantages in the nutritional management of surgical patients. PMID- 3090726 TI - A unique immune response control locus mapping with the H-2D class I region. AB - The immune response to the polysaccharide antigen Trinitrophenyl (TNP)-ficoll is controlled by two complementing loci in the murine major histocompatibility complex. One locus of control is present in the I-A subregion and the second is located between the S and D regions. A monoclonal antibody 48-21.7 was selected for its ability to significantly block the in vitro primary response to TNP ficoll. This antibody bound to antigen-presenting cells does not interfere with the presentation of other antigens. Experiments are presented to demonstrate that the monoclonal antibody 48-21.7 precipitates a unique protein of approximately 40,000 daltons. Sequential immunoprecipitation with monoclonal antibodies to the class I Db antigen and to relevant Ia antigens demonstrated no cross-reactivity. Amino acid sequencing has found unique amino acids to be present at three class I N-terminal invariant positions. These observations indicate the presence of a unique class I-like molecule coded for by genes mapping between S and D and involved in the response to the polysaccharide ficoll. PMID- 3090727 TI - Colon interposition for extreme short bowel syndrome: a case report. AB - Successful use of colon interposition has not been previously reported in an adult with short bowel syndrome. This article describes the course of a 34-year old woman who had interposition of an 18 cm segment of sigmoid colon between 5 cm of proximal jejunum and 7 cm of terminal ileum after midgut volvulus. The rationale for use of colon interposition in cases of extreme short syndrome is discussed. PMID- 3090728 TI - [A place to be--while they are building nursing homes]. PMID- 3090729 TI - [Intravenous administration of nitroglycerin to patients with unstable stenocardia]. AB - Thirty-two patients with unstable angina were given i.v. infusions of nitroglycerin (from 2 h to 9 days, an average of 62 h) under the control of the level of arterial pressure. Indications for i.v. administration of nitroglycerin were frequent attacks of angina of effort and at rest in combination with prolonged angina attacks which persisted in spite of treatment with nitrates of prolonged action, calcium antagonists and beta-blocking agents. A moderate decrease in arterial pressure without significant change in heart rate was noted against a background of nitroglycerin infusions. The best antianginal effect was achieved in patients with frequent angina attacks, and on the whole a stable state using i.v. nitroglycerin infusions was achieved in 2/3 of the patients. A low antianginal efficacy of i.v. infusion of nitroglycerin in patients with unstable angina was an unfavorable prognostic sign: in this group myocardial infarction developed approximately in half of the patients during their stay in hospital. PMID- 3090730 TI - [Clinico-functional characteristics of stenocardia and the effectiveness of its treatment with nitrong and erinit]. AB - A study was made of exercise tolerance and indices of central hemodynamics in 151 patients with "isolated" angina and its combination with cardialgia, arterial hypertension and postinfarctional cardiosclerosis. Daily attacks of angina of effort (III functional class) were noted in all the patients. In patients with "isolated" angina and angina in postinfarctional cardiosclerosis exercise tolerance was the lowest. It was the highest in angina combined with cardialgia. The lowest indices of cardiac output were observed in patients with "isolated" angina and angina in postinfarctional cardiosclerosis. The best effect of nitrate therapy was obtained in patients with typical angina. PMID- 3090731 TI - [Role of vasodilator agents in the complex treatment of circulatory insufficiency in patients with ischemic heart disease]. AB - The paper is concerned with the results of therapy of CHD patients with circulatory insufficiency using cardiac glycosides combined with a nitrate of prolonged action (sustak) and an arterial dilator apressin. Since the patients were advanced in years, sustak was given at average doses of 6.4 mg every 8 h and apressin at a daily dose of 75 mg. Additional treatment with vasodilators resulted in positive hemodynamic shifts in the patients with stage IIA and IIB circulatory insufficiency. The highest hemodynamic effect in therapy of marked circulatory insufficiency was observed in the patients with a low initial cardiac output and a high peripheral vascular resistance after multimodality therapy (cardiac glycosides, sustak and apressin). Changes in hemodynamics should be taken into account during therapy with vasodilators and control over their efficacy should be exercised. PMID- 3090733 TI - Effect of mitomycin C on the neural tube defects of the curly-tail mouse. AB - Around 60% of the mouse mutants called curly-tail, have tail aberrations in the form of a coil or a kink, with or without lumbosacral spina bifida, and rarely, exencephaly. These neural tube defects (NTD) are the result of an incompletely penetrant recessive gene. A single injection of various doses (1-6 mg/kg) of the DNA inhibitor mitomycin C was given to pregnant curly-tail mice on day 7, 8, or 9 of gestation, and its effect on the NTD of the embryos was noted. No dose used was lethal to the embryo. When given on day 7 or day 8, mitomycin C markedly increased the number of exencephalics, and additionally, on day 8, it reduced the number of posterior abnormalities. However, on day 9, no exencephaly was produced, and there was a drastic reduction in the number of tail and spinal defects, the overall incidence of NTD being as low as 15% with 2 mg/kg. A twofold effect of mitomycin C on the curly-tail embryos was thus observed--according to the time in development it was administered, firstly, a teratogenic effect, and later, a "remedial" or preventive effect. PMID- 3090732 TI - Transfer of valproic acid and its main active unsaturated metabolite to the gestational tissue: correlation with neural tube defect formation in the mouse. AB - The pharmacokinetics of the antiepileptic drug valproic acid (2-propyl-pentanoic acid; VPA) and its main active metabolite 2-en-VPA (2-propyl-2-pentenoic acid) in mouse serum and gestational material were studied and correlated with the drastic differences between the two compounds in their embryotoxicity. The peak levels of VPA reached after 0.5 hours were only slightly higher than that of 2-en-VPA (both in mother and gestational material). The free concentrations of VPA and 2-en-VPA in maternal serum also peaked at 0.5 hours. After that time the free maternal serum levels of 2-en-VPA decreased much more rapidly than the concentrations in the gestational materials. The area under the concentration/time curves (AUC) values of 2-en-VPA in mother and embryo were lower than corresponding values of VPA; the higher clearance of 2-en-VPA was predominantly due to an increased volume of distribution. Since we have previously shown that the peak concentrations and not the AUC values of VPA correlated with the teratogenicity of this compound, our present data indicate that the low teratogenic and embryotoxic potential of 2-en-VPA is a result of the intrinsic activity of this compound and not of lower peak concentrations reached in mother and embryo. PMID- 3090734 TI - Dazoxiben, UK 38,485 and aspirin: duration of effect for preventing thrombotic sudden death in rabbits. AB - The purpose of this study was to compare the effects of dazoxiben (DAZ), UK 38,485 (UK) and aspirin (ASA) in the prevention of thrombotic sudden death in rabbits. In anesthetized male rabbits, sudden death was produced by intravenous administration of 0.75 mg/kg arachidonic acid (AA). AA increased plasma TxB2 levels from 0.20 +/- 0.10 ng/ml to 8.75 +/- 1.79 ng/ml and produced a 42% reduction in the number of circulating platelets. Death occurred in all animals within 5 minutes. Administration of DAZ (8.6 mumole/kg) 15 min before AA prevented the increase in plasma TxB2, the thrombocytopenia and sudden death while pretreatment with DAZ 2 hr before AA did not. The administration of UK (8.6 mumole/kg) 15 min. 4 hrs or 8 hrs before AA resulted in 100%, 67% and 33% survival, respectively. ASA (110 mumole/kg) administered 2 or 24 hrs before AA inhibited the increase in plasma TxB2 and prevented the fall in platelet counts. All animals pretreated with ASA survived. These data demonstrate that DAZ and UK have only a short to moderate duration of action in preventing AA-induced increases in plasma Tx levels and thrombocytopenia. PMID- 3090735 TI - An ELISA test for the binding of von Willebrand antigen to collagen. AB - Collagen (soluble bovine tendon type I) coated onto microtiter plates binds von Willebrand antigen (vW:Ag) in a dose-dependent manner. An ELISA test was set up with both antibody and collagen coated microtiter plates. Test specimens assayed were: 1) normal plasmas, 2) type I vW plasmas, 3) type IIa vW plasmas, and 4) factor VIII concentrates (KoateR, Cutter; Conco-VIII, Green Cross). Normal and type I vW plasmas exhibited comparable values for vW:Ag in binding studies to both collagen and antibody-coated plates. Type IIa vW plasmas demonstrated decreased (less than 1/2) collagen to antibody-binding ratios. Ristocetin cofactor (VIII:RCO) levels in type IIa vW plasmas correlated with quantified collagen-binding levels. Factor VIII concentrates show variable results when comparing collagen and antibody-binding levels. A comparison of vW:Ag ELISA (antibody) with VIII:RCO shows ratios of 2:1 (KoatR) or 20:1 (Conco-VIII). Collagen-binding ELISA levels in concentrates show parallel decreases, reflecting presumed binding to collagen of only the high M.W. multimers. The vW:Ag collagen binding ELISA represents a possible replacement assay for the laborious and imprecise VIII:RCO method of measurement of in vitro vWf functional activity. PMID- 3090736 TI - [The short bowel syndrome in children]. PMID- 3090737 TI - [Propagation of viruses along neuron networks by transsynaptic passage--a contribution to the pathogenesis of rabies]. AB - Certain neurotropic viruses are carried along neuronal processes by the axonal transport mechanisms. Indirect morphologic evidence suggests that viral nucleic acid can be transmitted to other neurons by transsynaptic passage. Through this mechanism the viral genome can reach widespread and remote brain areas by propagation along neuronal networks in an intracellular milieu. This type of propagation does not require completion of full replication cycles for cell-to cell spread; transmission of infective viral nucleic acid is in itself sufficient. PMID- 3090738 TI - Evaluation of LD50 of some polyaminocarboxylic acids used as chelating drugs in metal intoxication. AB - The LD50 of the following metal-binding chelating drugs, EDTA, diethylenetriaminepentaacetic acid (DTPA), hydroxyethylenediaminetriacetic acid (HEDTA), cyclohexanediaminotetraacetic acid (CDTA) and triethylenetetraminehexaacetic acid (TTHA) was evaluated in terms of mortality in rats after intraperitoneal administration and was found to be in the order: CDTA greater than EDTA greater than DTPA greater than TTHA greater than HEDTA. A possible correlation between the toxicity and molecular structure of the compounds is discussed. PMID- 3090740 TI - [Optimization of the marginal adaptation of posterior composite fillings using side reflected light wedges]. PMID- 3090739 TI - [The Silicoater system: a new preparation method for split-free resin-metal bondings in dental prosthetics. Material for temporary crowns and bridges]. PMID- 3090741 TI - [Attitude toward oral implantology in German-speaking areas]. PMID- 3090742 TI - [Fluoride in oral prevention--today]. PMID- 3090743 TI - [Fluoride prevention--concerning the health risk]. PMID- 3090744 TI - [Practical realization of oral prevention. Struggle for a concept]. PMID- 3090745 TI - [Computer-assisted recording and evaluation of caries epidemiological data]. PMID- 3090747 TI - [Worldwide caries reduction--Germany tries to make contact]. PMID- 3090746 TI - [Worldwide caries diminish--why not in Germany?]. PMID- 3090748 TI - [The report "Care of the Aged": an ambiguous future scenario]. AB - The Dutch governmental report 'Care of the elderly' is evaluated in the light of the findings of the study 'The elderly and their health in the Netherlands, 1984 2000'. The latter delineates three scenario's, by which in the near future the need of provisions may develop. The reference-scenario assumes a stable, relative demand for provisions, the growth-scenario an increasing and the shrinkage scenario a decreasing demand. For economical and ideological reasons the Dutch government adheres to the shrinkage-scenario. Nevertheless, the same government also expresses severe doubts concerning the underlying assumptions. The proposed measures appear not to be consistent with the shrinkage-scenario. It is concluded that 'Care of the elderly' demonstrates ambiguity in its view on the future need of provisions by the elderly. This ambiguity appears to be largely determined by restricted financial and regulating means. PMID- 3090749 TI - Increased factor VIII as an index of vascular injury in cyclosporine nephrotoxicity. AB - Very high plasma concentrations of factor-VIII-related antigen (RAG) (VIII-RAG) were found in renal allograft recipients during periods of nephrotoxicity induced by cyclosporine. In eight recipients, who were investigated at weekly intervals, levels of factor-VIII-RAG fell toward normal as the dose of cyclosporine was reduced. Plasma levels of C-reactive protein, an acute phase reactant protein, were never raised in these recipients. These findings are further evidence that toxic doses of cyclosporine are associated with vascular injury. PMID- 3090750 TI - The genetic control of the antibody response to the Pa antigen in the rat. AB - The antibody response to the pregnancy-associated (Pa) antigen in the pregnant female segregated with the major histocompatibility complex (MHC) when the female progeny in the (PVG x WF)F1 x PVG testcross, in which the PVG strain is a low responder to Pa and the WF strain is a high responder, were mated to DA male rats. These results show that non-MHC immune response genes do not play a role, or at least any significant role, in the immune response to the paternal component of the placental antigens: the response approximates a unigenic trait with simple Mendelian segregation. Serological analysis showed that the antibodies formed by both the high responder (GMT 15, titer 1:32,768) and low responder (GMT 3, titer 1:8) female rats were directed against the Pa antigen. These findings show that the genetic control mechanism and the specificity of the antibody elicited by the placental antigen Pa are different from those in the responses to organ grafts and to soluble antigens. PMID- 3090751 TI - Compliance with penicillin prophylaxis by children with impaired splenic function. AB - 42 children with impaired splenic function were followed-up for 8 months for compliance with penicillin prophylaxis. Parents of 24 children (group A) chose a twice daily oral while parents of 18 children (group B) chose a 3-weekly injection regimen. The penicillin intake was checked by the presence of antibacterial activity in urine obtained at clinic visits. The clinics attendance rate for both groups was 92.7% and 94.9% respectively. For group A 44% of urines tested were positive indicating poor compliance with oral medication over the previous 5 to 16 hours. The educational level of parents and age and sex of children did not influence compliance. It seems safer, therefore, to use an intramuscular regimen rather than rely on oral prophylaxis in children with impaired splenic function. PMID- 3090752 TI - Bioenergetic and cardiovascular responses to exercise in residents at 2.850 m, with asymptomatic Chagas' disease. AB - Cardiovascular and energetic responses at rest, during 30 min of exercise (mechanical output: 125 watts) and for a subsequent recovery period of 5 min were compared in two groups, each comprising 21 residents at an altitude of 2.850 m. One group was in the asymptomatic phase of Chagas' disease with positive serological tests for T. cruzi, whereas the other was without Chagas' disease (negative serological tests). The two groups were similar as regards age, weight for-height, blood parameters, nutritional status and heart and lung functions, including heart rate and frontal plane QRS axis determinations. At rest, they differed in that maximal and minimal arterial blood pressures were slightly but significantly lower in the group with Chagas' positive serological tests than in the controls. During exercise and recovery, the only differences between them and the controls were that their minimal diastolic arterial blood pressure was significantly lower. In absolute values, the rises in arterial pressure due to exercise were exactly the same in the two groups. Maximal O2 uptake was identical in both groups, as was exercise steady state VO2. These findings indicate that the asymptomatic subjects with Chagas' disease had a normal work capacity and were not affected by high altitude. PMID- 3090753 TI - [Structural and functional characteristics of the cellular reaction of the bladder epithelium in the frog to calcium extraction from the apical and basolateral membranes]. AB - Extraction of Ca++ ions from cells of the frog urinary bladder serosa side is followed by an increase in the bladder wall permeability for water and inulin. Ultrastructural changes were observed, such as destruction of cell junctions, swelling of the cell and their organelles, reconstruction of the cytoskeleton elements. The free calcium Ringer solution injected in the bladder lumen does not change the permeability of the wall for water and sodium ions. In this case the cell response to the antidiuretic hormone decreases; the ultrastructure of cells and intercellular junctions is not disturbed; the distribution of intramembrane particles on the P- and E-faces of the apical membrane is normal. The above results indicate that there are qualitative differences in the cell response towards the extraction of Ca++-ions between the serosal and mucosal membranes. This also suggests that on the external surface of the apical membrane Ca++ ions may play a very important role in redistribution of intramembrane particles under the action of the antidiuretic hormone. PMID- 3090754 TI - [An unusual case of heavy alpha chain disease associated with amyloidosis]. PMID- 3090755 TI - [Catalytic properties of extracellular phenol oxidases from the higher basidiomycete Pleurotus ostreatus (Fr.) Kumm]. AB - Phenol oxidase preparations possessing high stability in the reaction of phenols oxidation are isolated from the culture filtrates of four strains of higher basidiomycete Pleurotus ostreatus (F r.) Kumm. The preparations are able to oxidize mono- and diphenols with different substituents in o-, m- and p-positions to phenol hydroxyls as well as o- and p-phenylene diamines. A change in the orientation of substituents in the substrate molecule is followed by a change in the mechanism of its oxidation. The enzyme activity is determined by the type of substituents in the phenol molecule: electron-withdrawing groups impede and electron-releasing ones facilitate the substrate oxidation. The Hammett equation is shown to be applicable for description of monophenol oxidation. An explanation of high values of positive deviations from it in the case of halogen-substituted phenols is suggested. A conclusion is drawn that Km of enzymes for oxygen determined from the full kinetic curves of O2 uptake with phenol redundancy are kinetic constants depending on the substrate structure. PMID- 3090757 TI - Post-transfusion hepatitis: a problem in Northern Ireland? AB - A retrospective analysis of post-transfusion hepatitis reported to us from 1980 through 1984 revealed 16 patients. We believe that this apparently low incidence is due to lack of notification and make a case for direct notification to us of any suspected cases. Disqualification of implicated blood donors is of prime importance in prevention of transfusion-associated hepatitis. PMID- 3090756 TI - [Isolation and immunological determination of retinol-binding protein in human plasma]. AB - A retinol-binding protein and prealbumin both in the homogeneous state are isolated from human blood serum. Immunization of rabbits is used to obtain antibodies against the retinol-binding protein; the highly specific method is developed for quantitative determination of the content of retinol-binding protein in human blood. The method may be widely applied in the biochemical and clinical practice. PMID- 3090759 TI - [Retrospective evaluation of the findings in male fertility disorders with special reference to spermiograms and hormone analyses]. AB - 736 ejaculates from 384 patients in the andrological outpatient clinic in Giessen were classified in fertile, subfertile and infertile Groups. Regarding volume, pH value and fructose content of the ejaculate no differences were found among the three groups. Important for the classification is sperm count/ml and the progressive motility. Additional Hormone analyses showed a negative correlation between sperm count and FSH-Values. Disturbances in spermiogenesis are often connected with high LH-Values. PMID- 3090758 TI - [Radiation and drug therapy of prostatic cancer]. PMID- 3090760 TI - [Exocrine and endocrine testicular function following unilateral torsion--a retrospective clinical study of 36 patients]. AB - Of 86 patients who had undergone unilateral testicular torsion the fertility in 36 patients could be examined 1-9 years later. The testis in 27 patients (= 75%) was surgically untwisted. Of 9 patients (= 25%) the testis was removed because of marked hemorrhagic infarction. Fixation of the contralateral testis was prophylactically performed in all cases. The testis of all patients who had undergone the detorsion within the first 22 h were saved and there was no significant difference of the testicular volume compared with the contralateral side. An atrophy of the contralateral testis following prophylactical fixation was never observed. In most of the 36 patients the fertility was diminished: Seminal analysis revealed an oligozoospermia in 44%, a teratozoospermia in 20%, an asthenozoospermia in 20% and a normozoospermia in 16% only. This result was independent of the duration of the torsion. There was no difference in the group of patients with detorsion and the group with orchidectomy. The endocrinological examination revealed a statistically significant correlation between FSH and sperm density and between FSH and the duration of the torsion. But both correlation coefficients were less than 0.5 and are therefore without any clinical relevance. Testosterone, LH and prolactin were normal in all cases. PMID- 3090761 TI - Experience with diagnostic related groups. The hospital administrator's view. PMID- 3090762 TI - Experience with diagnostic related groups. The practicing physician's view. PMID- 3090763 TI - Experience with diagnostic related groups. The health insurance industry's view. PMID- 3090764 TI - Long-term home health care for the geriatric population. PMID- 3090765 TI - [An intramammary implant in the prevention of infectious mastitis in cows]. AB - A sterile polyethylene device was introduced in the milk cistern of two mammary quarters of forty dairy cows. The cows were divided into three groups according to the length of exposure of the device in the cistern (3 days, 14 days, 365 days). The somatic cell counts were studied for a year in the first 10 ml fraction of milk and an increase in the somatic cell counts was found in the quarters having the intramammary device, as compared with the control quarters (having no devices). This difference was marked during lactation and prior to the onset of drying off. For the reduction in the frequency of occurrence of new natural intramammary infections, the activity of the device against S. aureus was limited and no activity against S. agalactiae was proved. The proportions of polymorphonuclears, round-cell elements and macrophages were histologically studied and compared for the udder quarters with and without the intramammary body in correlation with the time of exposure of the device to the milk cistern milieu. The most marked differences in favour of the udder quarters with the intramammary device were recorded in the alveoli containing more cells with a significant proportion of polymorphonuclear leucocytes. Small differences were found in the interstitial and subepithelial zone of the milk cistern. The activity of acid and alkaline phosphatase and adenosine triphosphatase was histochemically determined in the tissue structures of the udder and was found not to change under the influence of the device. Leucocytes and macrophages adhering to the surface of the body were observed under scanning electron microscope. PMID- 3090766 TI - [Decontamination of continual cell lines spontaneously infected with mycoplasmas]. AB - The continual cell lines of bovine kidneys MDBK and AUBEK, and porcine kidneys RPD and IBRS, spontaneously infected with Mycoplasma arginini and Acholeplasma laidlawii, were decontaminated by the method of selective elimination. Two elimination procedures were modified to be used for the decontamination: one based on the reduction of infection by the light treatment of the cultures, the other based on the selection of mycoplasma-free cell population through cell clonation. On the basis of a long-continued control of the cell clones a methodical procedure of the preparation of mycoplasma-free cell lines was worked out. PMID- 3090767 TI - [Residual chlorinated pesticides and polychlorinated biphenyls in the eggs and adipose tissue of wild birds]. AB - In 1983 and 1984, in the State Veterinary Institute at Jihlava, 129 samples of eggs of wild birds of 14 species were analyzed coming from different regions of the Czech Socialist Republic for the presence of residues of chlorinated pesticides and polychlorinated biphenyls (PCB). Apart from this, nine samples of hawk fat and 27 samples of buzzard fat were examined. The method of gas chromatography with a detector of electron capture was used for the analysis. The analyzed samples were found to contain residues of PCB, DDT (and mainly its metabolite DDE), HCB, alpha-HCH, gamma-HCH. No residues of other chlorinated carbohydrates were detected. The residue levels of these substances in the eggs and fatty tissues of different species of wild birds vary within a very wide range. A significant influence is exerted on these levels by the differences in food spectrum, the age of the birds, lack of food causing mobilization of food reserves, and mainly the environment where the birds live. The highest levels of residues were found in the eggs and fatty tissues of predatory birds with a narrow spectrum of food, i.e. those feeding on other birds (sparrow-hawk 33.00 mg.kg-1 in the dry matter of eggs, hawk 239.98 mg.kg-1 in fat) or those associated with water (great crested grebe 11.97 mg.kg-1, sea-gull 11.24 mg.kg-1 in the dry matter of eggs). Much lower levels of the residues of the chemicals were recorded in the species feeding mainly on small rodents (kestrel 0.681 mg.kg 1, buzzard 2.456 mg.kg-1 in the dry matter of eggs and 11.398 mg.kg-1 in fat). Some of the samples under study contained dead embryos. These embryos had particularly high residue levels, often higher than the levels regarded in literature as toxic. PMID- 3090768 TI - [The effect of ovarian steroids on the pharmacokinetics of Terguride in the rat uterus]. AB - The incorporation of 3H-17-beta oestradiol (3H-E2) and 3H-Tergurid (3H-Te) in the uteri of sexually immature rats was monitored for 16 hours following the treatment of the animals with Tergurid, a semisynthetic ergot alkaloid [chemically acid N-(D-6-methyl-8-isoergolin-I-yl)--N',N'-diethylurea maleate; VUFB-6638]. The differences in the incorporation of 3H-Te in relation to the presence of ovarial steroids (E2 and progesterone) were investigated for the same period of time in the adult ovariectomized rats. In all the time intervals under study, the average values of 3H-E2 activities in the uteri of juvenile rats treated with Tergurid were lower than in the controls. This decrease was statistically significant (P less than 0.05) eight hours after treatment. The time course of the incorporation of 3H-Te in the uteri of the experimental and control animals was about the same. The activities of incorporated 3H-Te in the uteri of adult rats treated with E2 were higher in all the intervals, the difference being statistically significant after two hours and 16 hours (P less than 0.05) and after four hours (P less than 0.01). Progesterone did not induce any significant differences in the incorporation of 3H-Te. These results suggest that the increased incorporation of Tergurid in the uteri of adult rats is due to a direct influence of E2. It has been demonstrated by trials on juvenile rats that Tergurid does not combine with oestrogenic receptors. As suggested by the decreased weights of the uteri of juvenile rats treated with Tergurid, the uterine cells are unable to react to exogenous administration of E2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090769 TI - Anaesthesia of the medicinal leech (Hirudo medicinalis). PMID- 3090770 TI - Incidental prostatic carcinoma: morphometry correlated with histological grade. AB - The histological grades of prostatic carcinoma, as defined by Gleason, were correlated with three methods of morphometry in 254 step-sectioned prostates obtained at autopsy. The variables studied were 1) the number of tumours in each prostate; 2) bilaterality and 3) tumour volume. Each characteristic yielded a statistically significant correlation with histological grade. The strongest correlations were obtained using tumour volume. These autopsy studied help to explain the inconsistent results obtained from morphometric analyses of surgical material, and lend support to the Gleason system as a means of predicting tumour behavior. PMID- 3090771 TI - Hepatic vascular endothelial cells heterogenously express surface antigens associated with monocytes, macrophages and T lymphocytes. AB - During studies of the antigenic and functional properties of hepatic sinusoidal lining cells in situ, we found that only the sinusoidal endothelial cells share antigens with a peripheral blood macrophage subset capable of presenting soluble antigens and triggering autologous mixed lymphocyte reactions. They were HLA-DR+, OKM1-, OKM5+. Vascular endothelial cells in the portal areas and central veins were HLA-DR+, OKM1- and OKM5-. The sinusoidal endothelial cells also expressed an antigen found on helper/inducer (OKT4 and Leu3 a) T lymphocytes. Thus, the present study suggests that endothelial cells in different anatomic compartments in the liver heterogenously express surface antigens associated with monocytes, macrophages and T lymphocytes and possess distinct immunological functions. PMID- 3090772 TI - Epithelioid malignant schwannoma. A study of 14 cases. AB - We report a light and electron microscopic, immunohistochemical, clinical and prognostic study of 14 patients with epithelioid malignant schwannoma. In 8 patients the tumour involved a major nerve. The tumours were rather small in most instances, the largest diameter being less than 5 cm in 7 cases. Light microscopically, they showed highly cellular areas of epithelioid, polygonal or rounded cells characteristically forming cords and rows and arranged in nodules of varying size. Spindle cell sarcoma areas as in classical malignant schwannoma were seen in 9 cases, and neurofibromatous areas in one case. Four cases were entirely epithelioid in appearance. Electron microscopically the epithelioid tumour cells showed nuclei with mostly even contours containing one or two trabecular or reticular nucleoli, cytoplasmic projections, intra-cytoplasmic myelin-like figures, intercellular junctions and discontinuous, sometimes multilayered external lamina material. The ultrastructural findings indicate that epithelioid malignant schwannoma is a tumour of neural crest derivation having features of Schwann cell differentiation. Immunohistochemically, S-100 protein was demonstrated in 7 tumours and neuron specific enolase in 3. There was a female predominance, 9/14, and a median age of 38.5 years (range 17-74). The extremities, including the hip and shoulder regions, were the most common sites, 12/14. The tumour proved highly malignant; 9 of 14 patients were dead at the time of follow-up and a high incidence of metastasis (7 of 14) was observed. PMID- 3090773 TI - Promoting effect of estrogen on regeneration of the liver transplanted to an ectopic site in mice. AB - A single oral administration of a pharmacological dose of estriol (E3) immediately after transplantation of small liver fragments of mice under the kidney capsule induced a remarkable growth of regenerating liver tissue. The hepatocytes were successfully arranged in cords with well developed sinusoids between them. The cytoplasm of the hepatocytes showed prominent basophilia. In mice injected with carbon intravenously, large numbers of carbon-laden endothelial lining cells and Kupffer cells appeared in the newly building sinusoids. E3 raised the mitotic activity of the regenerating hepatocytes markedly and for a long period. The act of E3 on mitosis was much more effective on the regenerating hepatocytes than on the recipient's own hepatocytes. PMID- 3090774 TI - Coronary atheroma in the cynomolgus monkey: predictive value of serum and cutaneous lipoprotein measurement. AB - Hyperlipaemia was induced by a high fat diet in 11 cynomolgus monkeys. Morphological study of coronary arteries was carried out in 5 coronary samples from these 11 monkeys. The degree of arterial involvement was compared with the serum and cutaneous lipoprotein levels. These experimental data confirm that cutaneous apoprotein B measurement is the best marker for evaluation of coronary atheroma. PMID- 3090776 TI - An autofluorescence method for the diagnosis of early ischaemic myocardial lesions. A systematic study on 732 autopsies, including 182 cases of sudden death. AB - A systematic study of an autofluorescence method is described to improve the early histological diagnosis of myocardial ischaemia. Our results on 732 autopsy cases including 182 cases of sudden death show that the autofluorescence examination of haematoxylin and eosin stained sections of the myocardium is not only reliable in the identification of recent ischaemic lesions, but contributes to a better histological evaluation. In 24 cases undetected by white light examination it allowed recognition of ischaemic lesions. PMID- 3090775 TI - A computerized histomorphometric study of the effects of intoxication with vitamin D3 or 1,25 (OH)2D3 on growth and dentin production of impeded and unimpeded rat incisors. AB - The effects of Vitamin D3 and 1,25(OH)2D3 intoxication on growth and dentinogenesis were studied in impeded and unimpeded rat incisors. Animals were intoxicated either with Vitamin D3 (2 mg/kg/day) or 1,25(OH)2D3 (400 ng/kg/day) for 19 days. Undecalcified transverse sections were obtained from all lower incisors. The outlines of all dental tissues were traced and fed into a computer which depicted the changes in all variables measured (circumference and cross sectional area of tooth, pulp and dentin, width of dentin, CEJ [cemento-enamel junction] diameter and maximal labio-lingual diameter). Eruption rates, which had been recorded previously every 48 h, were used to compute the physiological age of each tooth site, so that only areas of similar age be compared. Growth. External dimensions of all intoxicated teeth decreased as the experiment progressed in contrast with control incisors which continued to increase in size. This effect was more pronounced in unimpeded incisors and may be due to the inhibitory influence of 1,25(OH)2D3 on cellular proliferation at the apical progenitor end. Dentinogenesis. 1,25(OH)2D3 intoxication had no significant effect on the rate of eruption and dentin formation in both impeded and unimpeded incisors. The same was true for impeded incisors intoxicated with Vitamin D3 but, both eruption and dentin production rates were impaired in Vitamin D3 unimpeded incisors. PMID- 3090777 TI - Pelvic phleboliths and thrombosis. AB - Pelvic phleboliths are common and are generally considered to be harmless. Two cases are described where pelvic phleboliths were associated with thrombosis. PMID- 3090779 TI - Spread of the light response along the rod outer segment: an estimate from patch clamp recordings. AB - Longitudinal spread of the light response was studied using cell-attached patch clamp recordings from the outer segments of isolated rod photoreceptors from toad retina. The effective photon-collecting area over which photoisomerizations influenced the membrane current through the recorded patch of membrane was determined by measuring the probability of a detectable response as a function of flash photon density (i.e. a "frequency-of-seeing" experiment). The effective collecting area averaged 0.40 micron2, which corresponds to a total sampling length of approximately 1 micron for the patch electrode. PMID- 3090778 TI - Effect of aphidicolin and nucleotide analogs on the phage phi 29 DNA polymerase. AB - The drugs aphidicolin and the nucleotide analogs butylanilino dATP, butylphenyl dGTP, and butylphenyl rGTP inhibited the protein-primed replication of phi 29 DNA protein p3 in the presence of purified terminal protein p3 and phi 29 DNA polymerase p2. The effect of aphidicolin was mainly on the polymerization reaction by decreasing the rate of elongation. The nucleotide analogs inhibited both the formation of the p3-dAMP initiation complex and its further elongation, the latter being also due to a decrease in the elongation rate. When assayed with the phi 29 DNA polymerase as the only protein, all the drugs inhibited polymerization on activated DNA as well as the 3'----5' exonuclease activity of the polymerase, indicating that the target of the drugs is the phi 29 DNA polymerase itself. PMID- 3090780 TI - [Apolipoprotein A-I and high-density lipoprotein cholesterol in familial hyperlipoproteinemias]. PMID- 3090781 TI - [Combination of nitrates and calcium antagonists in the treatment of the angina pectoris syndrome]. PMID- 3090782 TI - [Digestive function of the small intestine and pancreas in rats on artificial feeding]. AB - Full-value diets of similar composition were given to male rats weighing 207-230 g, by intravenous (group 1) or intragastric (group 2) routes. The proportion of amino acids, fats and carbohydrates was 9.9:15.7:74.4 (with regard to their calorific value). The diet calorific value comprised 60.6 kcal/rat/day. An average mass increase in group 1 was 2.44 +/- 0.14 g/day, in group 2 - 1.75 +/- 0.11 g/day. The protein content and activities of alpha- and gamma-amylase, invertase, maltase, and glycil-L-leucine dipeptidase were assayed in the intestinal mucosa of the proximal portion of the small intestine in group 1 rats, while a decreased alpha-amylase activity in the distal portion of the small intestine was recorded in the animals of group 2. The mass of the pancreas in the rats of group 1 and 2 was authentically lower than in the control rats which received oral feeding with natural foods. The lowest mass of the pancreas was observed in the rats of group 1. Specific activity of trypsin, lipase and RNase in the pancreatic tissues of rats in groups 1 and 2 was similar. The results of the study have evidenced a lowered function of the digestive system under conditions of artificial feeding, especially in case of intravenous nutrition. PMID- 3090783 TI - Effects of oxygen on red cells during liquid storage at +4 degrees C. AB - Red cells collected in CPD and suspended in SAGM medium were stored in plastic (PVC) containers for 42 days at +4 degrees C. Comparison was made between aerobic storage (normal air exposure) and anaerobic storage (exposure to nitrogen gas). The air-exposed units showed a strong increase in pO2 and oxygen saturation as a result of oxygen penetration into the bags from outside. This resulted in a decrease in ATP and adenylate energy charge, a slower metabolization of adenine and hypoxanthine to AMP and IMP, respectively, and a faster decrease in red cell fluidity. To explain the findings it is concluded that aerobic storage causes an increased need of high-energy phosphate groups, possibly used for replacement of the phospholipid membrane bilayer or in repair of phosphate bonds in the cytoskeleton. It is further proposed that a slight formation of hydrogen peroxide from free oxygen radicals moderately increases the oxidation of reduced (GSH) to oxidized (GSSG) glutathione and slightly enhances the need for reduced nicotinamide-adenine dinucleotides mainly provided by increased flux through the pentose phosphate shunt. PMID- 3090784 TI - Flow cytometric analysis of erythrocytic D antigen density profile. AB - Red blood cells (RBC) were studied with flow cytometry (FCM) after staining with a directly fluoresceinated anti-D antiserum. The immunofluorescence distribution profiles were slightly asymmetrical, due to a significant, yet small skewness. This skewness was not associated specifically with D antigen positivity, making a homogeneous, normal D antigen distribution on the RBC very likely. With the exception of Du, D-positive RBC could always be distinguished from D-negative ones. FCM was successful in bringing the following phenomena to light: difference in mean fluorescence intensity between the different rhesus phenotypes, the D gene dosage effect, the depressing effect of C antigen on D antigenicity, the nonspecific attachment of IgG on (D-negative) RBC and rhesus mosaicism. The absolute number of D antigen sites could be calculated, using an absolute fluorescence standard. PMID- 3090785 TI - Starting a plasmapheresis program with hollow-fiber filtration. AB - In a routine donor center, a program of hollow-fiber filtration can be instituted. With the Organon Teknika PLASMAPUR system the collection of 600 ml plasma was completed within 50 min in 76% of the procedures. Changing the tubing set took 12-15 min. From the plasma a frozen cryoprecipitate is made with a recovery of 59%. After pooling, lyophilization and heat treatment, the recovery is 42%. PMID- 3090786 TI - Important parameters in plasma fractionation. AB - Important parameters in plasma fractionation are derived from the needs of providing assured quality and the operational requirements of good manufacturing practice. There are many inputs to quality assurance, collectively described as the quality design of the manufacturing process. Quality design is an all embracing concept depending on selection of source plasma, proper production facilities and equipment systems and highest pharmaceutical operational standards. The scientific process must meet the requirements of safety and efficacy of product and balance the competing parameters of purity, potency and yield within an acceptable economic framework. The paper illustrates problems within the theory of quality design through current experience in the production of immunoglobulin and factor VIII fractions. PMID- 3090787 TI - Non-A, non-B hepatitis: an update. AB - The definition of non-A, non-B hepatitis (NANB) is improved by further characterization of what it is not (like the delta agent or non-A epidemic hepatitis) rather than by providing convincing evidence of isolation of the agent responsible for blood transfusion- or blood product-related NANB or specific markers thereof. Yet, NANB research is in disquieting movement. Modern biotechnology yielded its blessings to the field. However, monoclonal antibodies and molecular probes will have to be evaluated with the same scrutiny that unmasked so many test systems and viral agents thus far. Recent victims appear to be published reports on NANB being identified as a retroviral agent and NANB virus being propagated in primary cultures of chimpanzee hepatocytes. Yet the application of these powerful new tools, together with the availability of cultured human and chimpanzee hepatocytes for propagation of the agent may improve the chances for substantial progress. Our finding of involvement of lymphocytes in transmission of the disease may add another approach to reach the ultimate goal of characterization of the causative agent and development of diagnostic methods to detect it in patients and biological materials derived from carriers of the disease. PMID- 3090788 TI - [Basal gonadotropin level and gonadotropin response to stimulation in patients with anorexia nervosa]. AB - Serum gonadotropin (GN) levels were examined before and after stimulation with luteinizing-hormone-releasing-hormone (LHRH) (100 micrograms/m2 body surface) in 25 female patients with anorexia nervosa (AN) and in 19 healthy young women. 12 patients were reexamined after clinical improvement. Basal GN levels and the luteinizing hormone (LH) response to stimulation were significantly lower in patients than in controls, whereas the response of follicle-stimulating hormone (FSH) to LHRH was normal. The GN response in patients was weight dependent, displaying an inverse correlation to the weight loss. After clinical improvement the GN response was significantly higher than in the acute stage of the disease. The data demonstrate that the activity of the hypothalamic-hypophyseal-gonadal (H H-G) axis, evaluated on the basis of the GN response to LHRH, depends on the body weight of the patient. Hence, the alteration in activity of the H-H-G axis seems to be a consequence, and not the cause of AN. PMID- 3090789 TI - Oxidative metabolism of encainide: polymorphism, pharmacokinetics and clinical considerations. AB - The 8-h urinary metabolic profiles of encainide and its oxidized metabolites, O desmethyl- (ODE), 3-methoxy-O-desmethyl- (MODE), N-desmethyl- (NDE) and N, O didesmethyl- (DDE) encainide were studied in a group of 112 normal Caucasians. Nine of these subjects (8%) were defective in their ability to 4-hydroxylate debrisoquine. The cumulative frequency distribution of the 8-h recovery ratio of encainide/ODE indicated two distinct populations in complete concordance with the debrisoquine phenotyping. The subjects with an 'extensive metabolizer' (EM) phenotype had a ratio from 0.003 to 0.9 whereas the PM group had values from 7.4 to 48. In addition, no MODE was detected in the urine from 'poor metabolizers' (PM). The oxidative metabolism of encainide, specifically the O-demethylation pathway, is, therefore, polymorphically distributed and controlled by the same genetic factor(s) that determine the 4-hydroxylation of debrisoquine. In EM subjects, ODE and MODE are the major metabolites in plasma and their concentrations are much greater than those of unchanged drug. As ODE is a more potent antiarrhythmic agent than encainide and MODE is at least equipotent, these metabolites significantly contribute to the overall antiarrhythmic effect in EM patients. The low plasma concentrations of ODE and MODE in PM subjects would be expected to result in inefficacious therapy when usual doses of encainide are administered. However, in such individuals, chronic oral therapy results in accumulation of unmetabolized encainide to far higher levels than in EM subjects. As encainide itself has intrinsic antiarrhythmic activity at these concentrations, this generally results in the desired clinical response. Despite pronounced interphenotypic differences in encainide's disposition and pharmacokinetics, the polymorphic oxidative metabolism appears to have limited consequences for the drug's clinical efficacy. PMID- 3090791 TI - [Assessment of thyroid parameters in aged patients with chronic diseases]. AB - Our results so far show a decrease of the T3 values by approx. 0.2 nmol/l. This decrease can be explained, on the one hand, by a shifting of biologically active T3. On the other hand, there are examinations that cannot prove any decrease of the biologically active, free T3. The explanation is found here by the restricted capacity of the rT3-degrading enzyme. According to this explanation, therapeutical consequences should not be drawn, but are rather dangerous. PMID- 3090793 TI - [Examination and classification of hand injuries]. PMID- 3090792 TI - Hominoids from the miocene of East Africa and the phyletic position of Kenyapithecus. PMID- 3090790 TI - Fever: is it beneficial? AB - Data obtained in lizards infected with live bacteria suggest that fever may be beneficial to their survival. An adaptive value of fever has also been inferred in mammals, but the results are equivocal. Findings that certain leukocyte functions are enhanced in vitro at high temperatures have provided a possible explanation for the alleged benefits of fever. However, serious questions exist as to whether results from experiments in ectotherms and in vitro can properly be extrapolated to in vivo endothermic conditions. Indeed, various studies have yielded results inconsistent with the survival benefits attributed to fever, and fever is not an obligatory feature of all infections under all conditions. Certainly, the widespread use of antipyretics, without apparent adverse effects on the course of disease, argues against fever having great benefit to the host. In sum, although fever is a cardinal manifestation of infection, conclusive evidence that it has survival value in mammals is still lacking. PMID- 3090794 TI - [Management of fresh hand injuries in free surgical practice]. PMID- 3090795 TI - [Hand injuries in a hospital without a hand specialist]. PMID- 3090796 TI - [Hand injuries at a specialized center]. PMID- 3090797 TI - [Primary management of hand injuries in Switzerland]. PMID- 3090798 TI - [Epidemiology and socioeconomic significance of hand injuries]. PMID- 3090799 TI - Studies upon the sites of bacterial breakdown of dietary purines within the gastrointestinal tract of the rat. PMID- 3090800 TI - Nitrite reduction related to serogroups in Neisseria meningitidis. AB - Among meningococci, nitrite reducing and non-reducing strains occur. From 1319 strains isolated between 1978 and 1984, all serogroup A, D and X isolates reduced nitrite. In strains belonging to the remaining serogroups, nitrite reduction was a variable characteristic. In group B strains isolated in 1978 and 1979 and possibly in group Z' (29 E) strains, sulfadiazine resistance seemed to be coupled to nitrite reduction. Differing from gonococci, N. meningitidis grew well under anaerobic conditions; its growth in the absence of atmospheric oxygen was not stimulated in the presence of nitrite. PMID- 3090801 TI - beta-D-galactosidase activity in streptococci of serological group B. AB - Group B streptococci isolated from humans differed significantly in beta-D galactosidase-activity from those of bovine mastitis. This could be demonstrated in a relatively simple and rapid test using a fluorogenic 4-methylumbelliferyl beta-D-galactoside conjugate. Only 10 (12%) of 82 group B streptococcal cultures from human produced beta-D-galactosidase. On the other hand, 74 (96%) of 77 "bovine" cultures formed this enzyme. Thus, beta-D-galactosidase activity could be used as an additional marker for the differentiation between group B streptococci of human and bovine origin. PMID- 3090802 TI - Partial characterization of leukocidin from Fusobacterium necrophorum. AB - Leukocidin from Fusobacterium necrophorum was produced in the diffusate of a dialysis culture. It was free from deoxyribonuclease, fibrinolysin, gelatinase, haemolysin, lipase, caseinase and endotoxin. The leukocidin had a molecular weight between 10,000 and 5,000 as estimated by membrane partition chromatography. It formed precipitin lines with anti-leukocidin-serum in double immunodiffusion tests. Mouse peritoneal cells were characteristically damaged by the leukocidin, as revealed by scanning electron microscopy. The damaged cells lost microvilli and suffered partial destruction of their cell membranes. PMID- 3090803 TI - Monoclonal antibodies against the K99 antigen of Escherichia coli for diagnostic purposes. AB - Hybridomas secreting monoclonal antibodies against the K99 antigen of Escherichia coli were produced by the fusion of spleen cells from immunized BALB/c mice with P3/X63-Ag8.653 myeloma cells. The seven hybridomas which produced the highest antibody titers in vitro, as detected by enzyme-linked immunosorbent assay (ELISA) and Perma slide agglutination test (PSAT), were chosen for antibody production in vivo. No cross reaction was observed with K88ab, F41 and P987 antigens in the ELISA. The titer of each ascitic fluid was established by the ELISA and the slide agglutination (SAT) tests. The two ascitic fluids with the highest titer in the SAT were incorporated into the set of antisera used for serotyping at our laboratory. The results were satisfactory both in terms of stability and specificity. PMID- 3090804 TI - Cell surface hydrophobicity of group D and viridans streptococci isolated from patients with septicaemia. AB - Sixty-three strains of Group D streptococci and viridans streptococci isolated from blood cultures during a two year period were typed to the species level with conventional biochemical tests and API Strep. Streptococcus faecalis was the most common species isolated followed by S. sanguis, S. mitis and S. constellatus (S. milleri). One of the two isolates of S. faecium was a contamination. The reported increasing frequency of this organism and other Group D and viridans streptococci as well as the association of S. bovis with malignant bowel disease indicate the need for full identification of streptococcal isolates from blood cultures. Pronounced surface hydrophobicity as measured with the salt aggregation test (SAT) was expressed by 59/63 (94%) of the blood culture isolates whereas strains isolated from commercial fermentation products and strains passaged several times were hydrophilic. In the presence of human serum albumin which binds to lipoteichoic acid only one strain decreased in surface hydrophobicity. The surface hydrophobicity of two strains even slightly increased indicating that lipoteichoic acid but marginally contributes to surface hydrophobicity of streptococcal cells from these species. PMID- 3090805 TI - Studies on the degradation of imipenem within serum and a renal kidney fraction. AB - The degradation of imipenem in vitro was analyzed using reversed-phase HPLC. The incubation of imipenem with a microsomal kidney fraction revealed the generation of two metabolites (UV-maxima at 275 or 308 nm, respectively). The metabolism of imipenem by the renal enzyme was completely inhibited by cilastatin (2 micrograms/ml). The lowest detectable inhibitory concentration of cilastatin was at 6.5 X 10(-10) M. The recovery of imipenem from serum was 52.6% after incubation for 2 h at 37 degrees C. The stability of the antibiotic within serum was improved by 13.9% in the presence of EDTA (10 mM) indicating a possible involvement of serum dipeptidases in the systemic breakdown of the imipenem molecule. PMID- 3090806 TI - [The auriculogram of Holstein-Friesian cattle]. PMID- 3090807 TI - Morphological findings in bovine cerebral theileriasis (BCT). PMID- 3090808 TI - Unidirectional uptake of L-amino acids at the basolateral membrane of gastric epithelia in anaesthetized dogs. PMID- 3090809 TI - [Lipid composition of plasma lipoproteins of dogs]. PMID- 3090810 TI - Relationship between factor XII, von Willebrand factor and postoperative deep vein thrombosis. AB - The development of postoperative deep vein thrombosis (DVT) was studied in 45 patients subjected to major abdominal surgery, 17 of whom showed signs of DVT as defined by 125I-fibrinogen test. The preoperative levels of von Willebrand factor (F VIII RAg) and platelets were higher in these 17 patients than in those remaining free from DVT. A contributing factor in DVT development thus may be more active primary haemostasis. Preoperative F XII levels were similar in the two groups, but the post-operative drop in F XII was more pronounced in the DVT group. An inhibitor of plasminogen activation behaved similarly in both groups. C1-inhibitor, the main inhibitor of the F XII-dependent clotting and fibrinolytic pathways, showed a typical acute-phase response postoperatively, without intergroup difference. The study suggested that F XII-dependent pathways play a role in the genesis of venous thrombi, at least in the postoperative period, though whether the postoperative F XII drop was due to a role in clotting or to fibrinolysis activation remains unclear. PMID- 3090811 TI - Infarction of a growth hormone-secreting macroadenoma during a TRH test. AB - Pituitary infarction occurring immediately after TRH injection (200 micrograms) is reported in a patient with gigantism due to a growth hormone-secreting pituitary macroadenoma. Evidence of infarction was seen in CSF and in serial CT scans. Regression of symptoms and sign of acromegaly, abolition of abnormal growth hormone secretion, and virtually complete anterior and partial posterior pituitary failure rapidly followed. The infarction was probably initiated by a hypertensive response to TRH. TRH testing in acromegalic subjects may require smaller doses of TRH to avoid unwanted pressor responses. PMID- 3090812 TI - Serum concentrations of 3,5,3',5'-tetraiodothyroacetate (T4A) in subjects with hypo-, hyper- and euthyroidism. AB - Some factors influencing serum 3,5,3',5'-tetradiodothyroacetate (T4A) concentrations were examined in hypothyroid, euthyroid and hyperthyroid human subjects. Serum T4A concentration was shown to be correlated with parameters such as serum, total and free thyroxine (T4) concentrations and thyroxine: thyroxine binding globulin ratio, which are indicative of the availability of T4 for peripheral metabolism. The relationship between T4A and these parameters was not a simple linear one; serum levels of T4A tended to show less variation from the normal range than did serum total T4 in hyperthyroid subjects. PMID- 3090813 TI - There is evidence that amniotic fluid arginine vasopressin is a marker for foetal stress in rhesus erythroblastosis. AB - In response to different stress stimuli the foetal neurohypophysis releases arginine vasopressin (AVP). Part of the AVP is cleared from circulation by urinary excretion into the amniotic fluid (AF). Increased AF AVP levels may therefore indicate foetal stress, all the more because AF AVP solely is of foetal origin. We therefore studied AF AVP levels in 13 patients with rhesus erythroblastosis from 22 to 34 weeks of gestation. Twenty-eight patients from 14 to 34 weeks of gestation served as controls. The AVP levels were measured by RIA. Spectral absorption curves were performed and delta/E values determined at 450 nm. Mean AF AVP levels in controls were 2.39 pg/ml and were not normally distributed. There was no significant change in AF AVP levels with different gestational age. If in rhesus erythroblastosis patients the delta/E value was low (n = 7; x = 0.048 +/- 0.007 SE), the AF AVP values were not increased. If the delta/E values were within zone III (n = 6; x = 0.22 +/- 0.035 SE), indicating severe haemolysis, the AF AVP levels were significantly elevated (4.7 pg/ml +/- 0.51 SE; P = 0.001). Linear regression analysis showed a significant correlation between delta/E and AF AVP values (P = 0.05; y = 1.94 +/- 10.88 x). We conclude that there is evidence for the role of AF AVP as a marker for foetal stress in rhesus erythroblastosis. PMID- 3090814 TI - A-ring reduction enhances the antigonadotropic potency of norethisterone. AB - To assess whether structural modifications on the A-ring of norethisterone (NET) could modify its antigonadotropic potency, comparative studies using NET, 5 alpha dihydro NET (5 alpha-NET) and its 3 beta,5 alpha and 3 alpha,5 alpha tetrahydro derivatives in castrated adult rats were undertaken. The antigonadotropic effect of these compounds was evaluated by measuring the serum and pituitary immunoreactive concentrations of LH and FSH following their chronic sc administration to animals depleted of progesterone receptors. The results demonstrated that 3 beta,5 alpha-NET and 5 alpha-dihydro-NET exhibited a significantly greater gonadotropic inhibiting activity as compared with that of their parent compound. The simultaneous administration of tamoxifen with 3 beta,5 alpha-NET resulted in a significant diminution of its antigonadotropic potency, particularly for LH. These data indicate that the potent antigonadotropic effect of 3 beta,5 alpha-NET metabolite was mediated via oestrogen receptors. The LH inhibitory activity of 5 alpha-dihydro-NET was not suppressed by the non steroidal antioestrogen administration, thus suggesting that 5 alpha-NET might exert its effect via androgen receptors. The overall data were interpreted as demonstrating that metabolic conversion products of NET exhibit potent antigonadotropic effect. The data are consistent with an A-ring enhancement of the antigonadotropic potency of this synthetic progestin and open an alternate approach to the development of fertility regulating agents. PMID- 3090815 TI - Studies on sickle cell heterozygotes in Saudi Arabia--interaction with alpha thalassaemia. AB - This study was conducted in the Eastern Province of Saudi Arabia where both thalassaemia and Hb S genes occur at a high frequency. In 171 Saudi Hb S heterozygotes, the range for Hb S was found to be 17-45% with a mean of 31.0%. Frequency distribution histograms showed a trimodal distribution. Peak A, B and C had 18-28, 28-35 and 35-45% Hb S values, respectively. Determination of alpha/beta ratio showed that these findings result from interaction of Hb S with the alpha-thalassaemia gene. Peak C with mean for Hb S of 40% consisted of a majority of individuals with no thalassaemia gene, and the alpha/beta ratio was 0.98% +/- 0.06. Peak B individuals were heterozygous for alpha-thalassaemia 2 with an alpha/beta ratio of 0.80% +/- 0.06 and peak A individuals were homozygous to alpha-thalassaemia 2 with an alpha/beta ratio of 0.58 +/- 0.08. The presence of alpha-thalassaemia 2 in homozygotes results in hypochromia and microcytosis, with little effect on haematological parameters. PMID- 3090816 TI - B-immunoblastic lymphoma arising in angioimmunoblastic lymphadenopathy. AB - We present a female patient with a B-immunoblastic lymphoma of the IgM-lambda type arising in angioimmunoblastic lymphadenopathy. An increased ratio of helper/inducer to suppressor/cytotoxic lymphocytes in the lymph node could have triggered the proliferation of B cells. Evolution of IgM cryoglobulinemia was paralleled by malignant transformation in the lymph node. A short-term in vitro chemosensitivity test could predict response to COP combination chemotherapy suggesting that in vitro chemosensitivity testing can be useful for the therapeutic management of angioimmunoblastic lymphadenopathy. PMID- 3090817 TI - B cell chronic lymphocytic leukemia and lung carcinoma with T-lymphocyte-rich pleural effusion in a single patient. AB - The case of a patient with B cell chronic lymphocytic leukemia (CLL) and T lymphocyte-rich pleural effusion secondary to carcinoma of the lung is presented. Monoclonal B cells were the main cell population in the peripheral blood and the helper/suppressor cell ratio of the residual T lymphocytes was lower than 1. On the contrary, T lymphocytes with helper phenotype were prevalent in the pleural fluid. The results indicate that local factors influence strongly the distribution of the lymphocyte subpopulations in different districts of the body and suggest that an etiopathogenesis unrelated to the B cell lymphoproliferative disease must be searched for, when a T-cell-rich pleural effusion is present. PMID- 3090818 TI - Leukaemic meningitis in chronic lymphocytic leukaemia. AB - A patient with chronic lymphocytic leukaemia (CLL) who developed leukaemic meningitis, after chemotherapy had successfully reduced the tumour load, is described. This progressed rapidly as basal meningitis and caused almost a complete obstruction of the lateral ventricles, palsy of several cranial nerves and deep coma. The diagnosis of leukaemic meningitis was nevertheless considerably delayed, as other forms of lymphocytic meningitis were excluded. Intrathecal methotrexate, followed by cranial irradiation led to complete resolution of neurological signs and symptoms and a rapid clearance of CSF of leukaemic cells. It is likely that immunological characterization of the CSF lymphocytes would help early diagnosis of such patients. PMID- 3090819 TI - Unexpected presentation of deep candidiasis in a recipient of a mismatched bone marrow transplant. AB - A Caucasian male of 37 years with acute non-lymphoid leukemia underwent a mismatched allogeneic bone marrow transplantation; he was in relapse but otherwise well. After conditioning with cyclophosphamide, total body irradiation and cytosine arabinoside, he received from his sister a graft depleted of T lymphocytes and cyclosporin A. Soon after transplantation he developed fever and a skin rash, followed, after response to high-dose steroids, by fever, acute renal failure, jaundice, progressive loss of consciousness and death after 2 weeks of transplant. Unexpectedly, autopsy revealed deep candidiasis of the liver and kidneys; here the histologic pattern was peculiar, because tubules were filled and occluded by Candida albicans organisms and hyphae. The uniqueness of this case and the fulminating clinical course did not allow to start an appropriate antifungal therapy. PMID- 3090821 TI - T activation in a patient with T cell chronic lymphatic leukemia. PMID- 3090820 TI - Acute myelocytic leukemia with acute aortic occlusion as presenting symptom. AB - In a 42-year-old Caucasian female, acute myelocytic leukemia (M2) presented as occlusion of the distal aorta and right iliac artery. She died after 10 days of respiratory failure. At postmortem examination the aortic wall contained multiple thrombi composed of fibrin and leukemic cells. There was no evidence of diffuse intravascular coagulation. Thromboplastic activity of the blast cells could have played a role in the formation of thrombi in the large vessels of this patient. PMID- 3090822 TI - Changes in patterns of leukaemia in Algeria, 1966-1985. PMID- 3090823 TI - Low-dose cytarabine in myelodysplastic syndromes and acute leukemia. A comment. PMID- 3090824 TI - The diagnostic usefulness of measuring antineutrophil antibodies in neutropenic patients. AB - We prospectively evaluated the usefulness of measuring antineutrophil (PMN) antibodies in patients with neutropenia by a sensitive immunoassay. The result of the immunoassay were compared to a standard leukoagglutination test. Thirty-two patients with neutropenia were studied. The mean value (+/- 1 SD) for PMN-bound IgG for 43 normal controls was 121 +/- 29 fg/PHN. All fifteen patients with immune neutropenia had elevated plasma levels of anti-PMN antibody (191-2,000 fg/PMN). The leukoagglutination assay was positive in 10 of these 15 patients. In 17 patients with nonimmune neutropenia, the mean value (+/- 1 SD) for PMN-bound IgG was 120 +/- 22 fg. Seventeen patients with sero-positive rheumatoid arthritis but normal PMN counts were also studied. These patients' plasmas bound 447 +/- (1 SD) 201 fg IgG/PMN. The leukoagglutination test was negative in these patients. Our study shows that the immunoassay is more sensitive than leukoagglutination testing for diagnosing immune neutropenia. Nonimmune, neutropenic patients' plasmas showed no increased reactivity. In nonneutropenic patients who have high titers of rheumatoid factor, immunoreactivity against PMN is measured by the immunoassay, but not by leukoagglutination testing. Binding assays may be more sensitive than leukoagglutination testing for measuring anti-PMN antibodies; however, in some cases, specificity of such testing may be increased with leukoagglutination testing. PMID- 3090825 TI - Hereditary leaky red cell syndrome in a Swiss family. AB - A Swiss family was found to have a hereditary hemolytic disorder associated with excessively leaky red cell membranes. Hemolysis was mild and fully compensated. Membrane lipid analysis revealed an increased phosphatidylcholine:phosphatidylethanolamine ratio. Membrane leaks included an increased permeability to sodium, potassium, calcium and, possibly, creatine. It is suggested that in hemolytic states, the combined finding of reticulocytosis and normal red cell creatine might be an easily obtainable clue to the presence of a leaky red cell syndrome. PMID- 3090826 TI - Correlative patterns of leukocyte counts at presentation and relapse in acute myelogenous leukemia. AB - Patients with acute myelogenous leukemia (AML) present with various levels of peripheral leukocyte and myeloblast counts which relate to their clinical outcomes. We have compared leukocyte and blast cell counts at the times of presentation and relapse and demonstrated that the pattern of first relapse in AML is not random; the leukocyte/blast counts at presentation and relapse in AML are associated, indicating the stability of this clinical parameter. Thus, levels of leukocytes and blasts may reflect heritable biologic characteristics of the leukemic clone. Recognition that the magnitude of the initial leukocyte count in AML is a prognostic factor which correlates with the pattern of relapse and remission duration in AML suggests that this feature should provide a useful clinical and biologic index for stratifying patients with AML. PMID- 3090827 TI - T lymphocyte subsets and platelet-associated IgG in idiopathic thrombocytopenic purpura: effect of splenectomy. AB - The modifications of cell-mediated immunity in idiopathic thrombocytopenic purpura (ITP) were investigated using the technique of Moretta et al. [J. exp. Med. 151: 969-974, 1980] to study T lymphocyte subsets in 35 ITP subjects at various clinical stages. In all these patients, platelet-associated IgG (PAIgG) were measured by a complement lysis inhibition technique. Untreated ITP patients did not show significant modifications of T lymphocyte subsets. Patients with thrombocytopenia not responsive to corticoids or splenectomy and increased PAIgG levels showed significant reduction of Fc-gamma-bearing T lymphocytes (T-gamma). Patients 'cured' by splenectomy (12 out of 17) showed a normal PAIgG level, a marked increase of T-gamma cells and a reduction of T-mu cells; patients 'not cured' by splenectomy showed an increased PAIgG level and a reduction of T-gamma cells. An increase of PAIgG levels and a reduction of T-gamma cells were found in 2 splenectomized patients after relapse. An association between chronic nonresponsive ITP and decrease of T-gamma cells was established. PMID- 3090828 TI - OKT4+ chronic lymphocytic leukaemia cells display different reactivity with selected monoclonal antibody combinations. AB - Four cases of chronic T lymphocytic leukaemia are characterized by selected monoclonal antibody combinations and double-fluorescence studies. We found 3 possible combinations: OKT4++ Leu8++ Leu9+, OKT4++ Leu8+ Leu9- and the OKT4++ Leu9++ Leu8- phenotypes are correlated with different biological aspects of the disease. No markers of T cell activation were found, and serological examinations did not reveal anti-HTLV-I antibodies. In considering a larger number of patients, multiparametric analysis could be useful to better classify this heterogeneous type of leukaemia. PMID- 3090829 TI - Estrogen and progesterone receptor guideline for tamoxifen therapy in chronic lymphocytic leukemia: a pilot study. AB - We studied estrogen and progesterone receptors (ER, PR) in 23 patients with chronic lymphocytic leukemia (CLL) and evaluated the results of this determination with other clinical and laboratory parameters. ER and PR activity was found respectively in 12 out of 23 (52%) and 6 out of 23 (26%) of the patients with a range between 2 and 23 fmol/mg protein (mean 10.3 fmol/mg) for ER and 18 and 92 fmol/mg (mean 41.8 fmol/mg) for PR. No correlations between ER/PR status and other parameters such as age, sex, stage, androgen and glucorticoid receptors (AR, GR), lymphocytic count or plasma estradiol and progesterone levels were noted. Seventeen consecutive patients out of 23 with a known receptor status and 1 with an unknown receptor status had been treated with tamoxifen 30 mg/day for 3 months. No objective response was achieved, despite some occasional reports of the literature. PMID- 3090830 TI - Antithrombin III during high-dose cytosine arabinoside therapy with or without asparaginase. AB - Fourteen patients with hematologic neoplasia (11 acute myeloid leukemias, 2 non Hodgkin's lymphomas and 1 blast crisis of chronic myeloid leukemia) who underwent high-dose cytosine arabinoside (HIDARAC) therapy with or without sequential asparaginase (ASNase) were investigated in order to evaluate liver toxicity and a possible decrease in antithrombin III (AT III) plasma level. AT III was found decreased only in patients who received ASNase, whereas HIDARAC alone did not influence AT III levels. It is pointed out that a single dose of ASNase seems to be sufficient to induce a decrease in AT III. A mild and transient liver toxicity due to HIDARAC therapy does not seem to be of any clinical relevance. PMID- 3090831 TI - A histochemical localization of acetylcholinesterase and cholinesterase activities in mammalian kidneys. AB - An acetylcholinesterase (AChE) activity and a cholinesterase (ChE) activity were localized in mammalian kidneys, using a modified histochemical method of Koelle. The animals studied were mouse, hamster, cat, rat, and guinea pig. The kidneys were excised after in situ perfusion and fixation to eliminate AChE and ChE activities of blood. We carried out a relatively long incubation (up to 4 h) to detect weak AChE and ChE activities in the tissue. The differences in enzymatic activities in the kidneys from these 5 animals were important. The AChE activity was localized in the glomerulus (mouse, hamster, cat, and rat) and in the tubule (mouse, hamster, and rat). The ChE activity was also localized in the glomerulus (mouse and rat) and in the tubule (mouse and cat). An important nonspecific esterase activity was observed in the tubules of rat, guinea pig, and cat. In the thin segment of the loop of Henle, except of cat kidney, no esterase activity at all was observed. Electron microscopy revealed that, in the mouse kidney, both AChE and ChE activities were localized in the endoplasmic reticulum of glomerular endothelial cells and mesangial cells. (An AChE activity was localized mainly in mesangial cells, while ChE activity was localized mainly in endothelial cells). AChE and ChE activities were also localized in the endoplasmic reticulum of tubule cells. PMID- 3090832 TI - Distribution difference of lectin binding in salivary gland treated with sialidase and trypsin. AB - Histochemical evaluation of complex carbohydrates in the salivary glands from rodents following sialidase and trypsin treatment were reported by the use of lectins binding technique which specifically link to corresponding sugar residues in macromolecules. Lectin staining in salivary gland generally increased following 1 h sialidase treatment, particularly in guinea-pig specimens. Lectin staining followed by treatment of trypsin (30 min) showed in increase in staining which is characteristic of UEA-I lectin. In long duration treated sections, by either sialidase or trypsin, lectin staining usually decreased in salivary glands. In the present study, complex carbohydrates of salivary glands may be hydrolyzed and degraded by sialidase and trypsin treatments, and lectin binding affinity is then also enhanced due to exposed sugar residues in complex carbohydrates. PMID- 3090833 TI - Studies on the actions of glutaraldehyde, formaldehyde, and mixtures of glutaraldehyde and formaldehyde on tissue proteins. AB - The effects of aldehyde fixation on tissue proteins was studied using SDS polyacrylamide gel electrophoresis. Fixation with low concentrations of formaldehyde or glutaraldehyde had only a slight effect on the protein banding pattern. On the other hand, most of the original protein bands were absent after a short treatment with mixtures of formaldehyde and glutaraldehyde. Spectral absorption measurements showed a stronger absorption at both gamma = 280 nm and gamma = 235 nm with the glutaraldehyde-formaldehyde mixture than with glutaraldehyde alone. PMID- 3090834 TI - Natural cysteine proteinase inhibitors reduce lectin induced lymphocyte stimulation. AB - Lymphocyte stimulation by lectins can be inhibited by several synthetic inhibitors of proteolytic enzymes, notably those of cysteine proteinases. The effects of naturally occurring enzyme inhibitors are less well known. The effect of the neutral low-molecular weight cysteine proteinase inhibitor (NCPI) recently purified from lymph nodes and spleen was therefore investigated. Cultured peripheral blood lymphocytes were stimulated by PHA or ConA in the presence or absence of NCPI and the incorporation of 3H-thymidine was measured. NCPI was found to inhibit these lymphocyte responses in these circumstances. PMID- 3090835 TI - [Water-induced metachromasia of thionine and methylene blue in histologic preparations]. AB - The metachromatic staining of histological preparations of tissues of lung and rib by thionine and methylene blue has been investigated. The metachromatic effect is caused by the distribution of monomer, dimer, and higher aggregates of the adsorbed dyes. This distribution is primarily influenced by the structure of the biopolymers, which adsorbs the dye cations. It is strongly modified by the water content of the media used for differentiation and embedding. PMID- 3090836 TI - [Histochemical phenoloxidase demonstration in tumors of the melanocytic system]. AB - Investigations of tissues from a naevus pigmentosus and 5 malignant melanomas were carried out. In malignant melanomas, the number of phenoloxidase reactive cells and the quantity of preformed pigment are very variable. It is discussed whether the in vitro phenoloxidase reactive cells and the in vivo pigment formation can be interpreted as expression of a cell mediated immunological defence reaction. PMID- 3090837 TI - [Relation between the labeling index and thymidine incorporation in cultured islands of Langerhans of the rat: stimulation of DNA synthesis by EGF-S3]. AB - DNA synthesis and labelling index of isolated neonatal rat islets were investigated during a 4 to 5 culture period in TCM 199 (10 mmol/l glucose) under selected conditions, as change of serum concentration in the medium or addition of a proliferation stimulating fraction. Additionally it should be proved whether the DNA-synthesis of pancreatic islets, measured as [3H]-thymidine incorporation, is representative for the amount of cells during the S-phase (= "growth fraction"). There is a correlation between the incorporation of [3H]-thymidine into the TCA-precipitate and the labelling index of islets determined on HE stained radioautographs. For this reason and because of being less time consuming, the measurement of DNA synthesis is a suitable screening method for selection of factors increasing the growth fraction of pancreatic beta-cells. Only the addition of FGF-S3 (growth stimulating raw prepared isolated from bovine brain) during culture caused a significant increase of DNA synthesis and labelling index of the islets. The labelling index of radioautographs stained by immunofluorescence method for insulin did not differ significantly from that determined at HE-stained radioautographs. Insulin secretion and content of the islets were not influenced by the addition of FGF-S3. PMID- 3090838 TI - [Interaction of endothelial and smooth muscle cells of the pig aorta in primary culture]. AB - In primary coculture of endothelial and smooth muscle cells, the muscle cells preserve their specialized phenotype (high myosin content) contrary to a pure smooth muscle cell culture. The addition of thrombin to the coculture-system results in loss of specialized phenotype of smooth muscle cell i.e. the relative myosin content decreases. PMID- 3090839 TI - The effect of sympathetic denervation with 6-hydroxydopamine on the ventral prostate of the rat. AB - The effect of chemical sympathectomy with 6-hydroxydopamine (6-OHDA) on the ventral prostate of the rat was studied. A dose of 50 mg/kg i.v., which was repeated after 1 week, was effective enough to produce total disappearance of sympathetic nerves. Reappearance of nerve fibres was evident 2 weeks after treatment. Dilation of prostatic alveoli was noted 1 week after denervation. It is concluded that the absence of normal sympathetic innervation prevents the emptying of the rat prostate. PMID- 3090840 TI - [Histochemical localization of prostaglandin synthetase in various organs in swine and guinea pigs]. AB - The activity of prostaglandin synthetase was studied according to the histochemical method of Janszen and Nugteren (1971), in author's own modification, in the lungs, arteries and parotid gland of the pig and in the same organs of the guinea pig. Additionally, the seminal vesicles of guinea pig were subject to investigation. A high activity of this enzyme has been found in the endothelial cells of the arteries in both species and a lower activity in the non striated muscles of the artery wall. A high enzymatic activity has been also observed in the epithelial cells lining the bronchi and bronchioles of the lungs and in the ductus parotidicus of the parotid gland in both species, as well as in the epithelial cells of seminal vesicles in the guinea pig. A weaker, but distinct activity, has been observed in the cells of vesicles of pig parotid gland, and in the cells of stroma of guinea pig seminal vesicles. PMID- 3090841 TI - [A fluorescence phenomenon of nucleoprotein shown by illuminated living cells]. AB - Living cell nuclei supravitally stained with fluorochromes exhibit a rapid fluorescence fading during continuous light or u.v. illumination. Subsequently the fluorescence intensity is transitory restored due to increased influx of new dye molecules and their interaction with nucleoproteins. This effect is interpreted as photodynamic (photosensitized) action concerning nuclear macromolecules. It can be shown with different intercalating and nonintercalating fluorochromes. Continued illumination causes cell damage and cell death. Fractionated illumination allows to investigate fluorescence recovery and other restitutional processes on the level of living eucaryotic cells. PMID- 3090842 TI - Investigation of hycanthone binding to DNA in chromatin with different supra organization, composition, and function. AB - Hycanthone is a drug used for the clinical treatment of schistosomiasis, although inducing chromosomes breaks and mutagenesis when it enters the DNA double helix. Based on visual observation of characteristics of basophilia and anisotropy after toluidine blue staining, a preferential binding of hycanthone to heterochromatin could be demonstrated for the nuclei of the Malpighian tubules of Triatoma infestans. In other cellular systems like cattle kidney cells in culture, plant cells, and mouse lymphocytes, the drug could be demonstrated to bind heterochromatin and euchromatin, irrespective of the packing state of the latter. When penetrating the various heterochromatin types (with the exception of T. infestans), the drug induced a chromatin loosening that could favor incidence of chromatin breaks. The variation of hycanthone binding to DNA in different cell types is possibly related to differences in composition, stereo-arrangement and stability of the DNA-protein complexes involved. PMID- 3090843 TI - PEEP reverses nitroglycerin-induced hypoxemia following coronary artery bypass surgery. AB - Intravenous nitroglycerin is increasingly used during and after cardiac surgery to control blood pressure and improve subendocardial and peripheral circulation. A dramatic decrease in arterial oxygenation has, however, been reported in a number of poorly controlled clinical trials. In the present investigation 16 patients were studied 2-4 h after coronary artery bypass procedures. All were treated with a continuous infusion of nitroglycerin (1 microgram X kg-1 X min-1). Utilizing an on-off-on drug design, it was clearly established that nitroglycerin depresses arterial oxygenation by increasing the pulmonary venous admixture. Three possible underlying mechanisms are discussed, but at the present time no firm conclusion can be drawn as to the nature of the changes. Eight patients were ventilated with 1 kPa (10 cmH2O) positive end-expiratory pressure (PEEP) during the nitroglycerin infusion. PEEP-ventilation reversed nitroglycerin-induced changes in arterial oxygenation and pulmonary shunting without adversely affecting hemodynamic stability. PMID- 3090844 TI - Gas exchange and lung morphology after surfactant replacement in experimental adult respiratory distress syndrome induced by repeated lung lavage. AB - Severe respiratory insufficiency was induced in adult guinea pigs by repeated lung lavage. The animals were then ventilated for 75 min with 100% O2, insufflation pressure 28/6-8 cmH2O (2.7/0.6-0.8 kPa), frequency 30/min, and 33% inspiration time. One group of animals (I) was treated with protein-depleted porcine surfactant, prepared by a combination of sucrose-gradient centrifugation, heating to 90 degrees C, and chloroform/methanol extraction. Another group (II) received the phospholipid fraction of porcine surfactant, isolated from minced lungs by chloroform/methanol extraction and liquid-gel chromatography. Surfactant was administered in two 1-ml doses (lipid concentration 90 mg/ml) instilled via the tracheal cannula about 15 and 45 min after the lavage procedure. Non-treated, lavaged animals served as controls. After 75 min of ventilation, control values for PaO2 and PaCO2 were 13.3 +/- 6.8 and 6.8 +/- 2.3 kPa (mean +/- s.d.), respectively. The corresponding values in Group I of surfactant-treated animals were 52.9 +/- 7.7 and 4.4 +/- 1.1 kPa, in Group II 53.5 +/- 7.3 and 4.8 +/- 1.3 kPa (P less than 0.02-0.002). The two groups of surfactant-treated animals also had significantly improved alveolar air expansion in histological sections, as reflected by increased alveolar volume density (0.67 +/- 0.05 and 0.62 +/- 0.11 vs 0.45 +/- 0.08 in controls; P less than 0.002). The benefits of surfactant replacement in this experimental model were thus similar to those previously observed in animal models of neonatal surfactant deficiency as well as in babies with respiratory distress syndrome (RDS). Our data suggest that surfactant replacement might have a therapeutic effect also in clinical adult RDS. PMID- 3090845 TI - Alfentanil v. isoflurane for outpatient arthroscopy. AB - Alfentanil by continuous intravenous infusion and isoflurane have been compared as anaesthetic agents for outpatient arthroscopy. In 42 patients, divided at random into two groups, anaesthesia was induced with methohexitone and vecuronium bromide, and, after intubation, maintained with nitrous oxide 66% in oxygen combined with alfentanil or isoflurane. Alfentanil was given before intubation (1 mg), as a loading dose before starting surgery (50 micrograms kg-1) and by a continuous infusion at a rate of 1 microgram kg-1 min-1. Isoflurane was given in a concentration of 0.9% as a maintenance dose. Awakening from anaesthesia was more rapid with alfentanil than with isoflurane. Recovery tests were applied in the recovery room. Both anaesthetic techniques provided satisfactory anaesthesia and rapid recovery. All patients but one were content with the anaesthesia. The patients who received isoflurane scored better in the recovery tests in the first 3 h, but after 3 h there was no difference between the groups. The alfentanil group showed a higher incidence of nausea and/or vomiting: 45% compared to 14% in the isoflurane group. PMID- 3090846 TI - Reversal of the cerebral effects of diazepam in the dog by the benzodiazepine antagonist Ro15-1788. AB - In six dogs initially anesthetized with halothane-N2O-O2 for surgery and maintained during the experiment with high spinal anesthesia and local infiltration, diazepam 3.0 mg X kg-1 converted the EEG from an awake to a sleep pattern. This was accompanied by a significant 21% reduction in cerebral metabolic rate for oxygen (CMRO2) and a 15% reduction in cerebral blood flow (CBF). Substituting nitrous oxide 70% for nitrogen had no additional cerebral effects. The benzodiazepine antagonist Ro15-1788, 2 mg, completely reversed the effects of diazepam on the EEG, CMRO2 and CBF. Cerebral biopsies taken at the end of the study revealed modest but significant decreases in ATP and the energy charge along with increases in AMP, lactate and lactate/pyruvate (L/P) ratio. These changes are unexplained and suggest a possible disturbance in oxidative phosphorylation produced by Ro15-1788 preceded by diazepam. PMID- 3090847 TI - [Blood typing of a Hansen population in Guadeloupe (F.W.I.)]. AB - The target of this survey carried out in Guadeloupe (F.W.I.) is to search for eventual relationship between leprosy forms and ethnic features--Made in people subjected to same environmental factors, such a study avoids usual bias of investigations on the epidemiological aspect of "racial" factors. The 1522 investigated patients have been divided into 2 categories: allergic paucibacillary (Mitsuda +), and anergic multibacillary (Mitsuda -) patients. -). Three parameters were studied: morphological type empirically determined according to cutaneous pigmentation; ABO blood groups; and Rhesus phenotype. The results bring to the fore: Significant linkage between clinical forms and morphotype: the dominant Caucasian morphological typed subjects, with integument poor in melanin, are more numerous among multibacillary patients. This might confirm high sensitiveness of Caucasians to leprosy. No significant linkage between clinical forms and ABO blood groups. Nevertheless, variations are found already reported in more homogeneous populations: predominance of A group in multibacillary patients, of B and O groups in paucibacillary patients. Significant linkage between clinical forms and Rhesus phenotype. But this link does not seem to be imputable to ethnic factors because clinical forms distribution is the same in ccDee sub-population (the most frequent in West Africa), and in ccddee subpopulation (quite frequent phenotype in West Europe). In fact, only the ccDEe phenotype sub-population is significantly different from all the others, because multibacillary forms are particularly frequent (49.3%) and strike evenly women and men in this sub-population. PMID- 3090848 TI - Acid maltase deficiency in adults. A study of five cases. AB - Five adult patients with the myopathic form of acid maltase deficiency are described. In three, the clinical onset dates back from youth with progressive proximal weakness while in the other two, the first symptoms occur after the age of 20 years. Respiratory insufficiency is a direct cause of death in one young adult male and plays an accessory role in the death of an older female patient with an interauricular septal defect. A unilateral diaphragm paralysis is noted in a third patient. A vacuolar myopathy is easily detected in the young adult patients but minimal or moderate lesions are encountered in other muscles or in the older patients. Electron microscopy of muscle and skin biopsies and the assay of acid maltase on muscle completed by the action of antibodies directed against acid maltase represent much more reliable criteria which will confirm the diagnosis. Therefore, when dealing with the heterogeneous group of limb-girdle myopathies, it is necessary to use all adequate diagnostic methods in order to avoid false negative results. The importance of making a correct diagnosis stems from the fact that the respiratory insufficiency should be recognized in order to try to avoid severe complications. PMID- 3090849 TI - Conization by carbon dioxide laser or cold knife in the treatment of cervical intra-epithelial neoplasia. AB - In a randomized trial concerning 123 women with CIN, 59 were treated with laser conization under colposcope without further hemostatic remedy and 64 with cold knife conization guided by Schiller's iodine dyeing supported by side sutures, vaginal packing and postoperative oral administration of tranexam acid. Follow-up with colposcopy and cytology was done 3 and 12 weeks post-conization and then every 6 months. The average follow-up period was 36 months (28-48). Peroperative bleeding was rather less pronounced in the laser group. Postoperatively, however, bleeding requiring treatment was significantly less common in the laser group (5%) than in the cold knife group (17%). The recurrence rate of CIN was 7% in the laser group and 10% in the knife group. Stenosis of the cervical canal developed in 7% of the patients in the laser group and in 3.5% in the knife group. After 12 weeks the squamocolumnar junction was visible in its full extent in 66% of the laser treated patients compared with 38% of the cold knife treated patients. It is concluded that laser conization is a safe procedure even without hemostatic procedures other than the coagulation abilities of the laser beam itself, as used in this work. PMID- 3090850 TI - Gonadal steroids, gonadotropins and endometrial histology in postmenopausal women with malignant ovarian tumors. AB - The concentrations of FSH, LH, 17-beta-estradiol (E2), estrone (E1) and progesterone (P) were measured in peripheral and ovarian vein sera obtained at preoperative pelvic angiography from 5 postmenopausal women with malignant ovarian tumors. In 5 others the concentrations of E2, P and testosterone (T) were also measured in ascitic fluid collected at laparotomy. The investigation showed that most of these patients had increased concentrations of E2 and/or E1 and P as well in the peripheral blood. Significant gradients between the ovarian and peripheral vein concentrations were found for E2 and for P. High levels of E2, P and T were found in the ascitic fluid. FSH and LH levels were often lowered in peripheral blood compared with normal menopausal values and a gradient to ovarian tumor venous blood - with lower concentrations in the blood coming from the tumors, was found. Endometrial histology showed signs of steroid stimulation. These cases indicate that malignant ovarian tumors and/or the ovaries harboring them, are often capable of producing different sex steroids. These steroids may be found in the peripheral blood and in the ascitic fluid compartment and therefore may be used as tumor markers. The steroid production is probably not autonomous, but gonadotropin-dependent. PMID- 3090851 TI - Long-term treatment with combined oral contraceptives and cigarette smoking associated with impaired activity of tissue plasminogen activator. AB - The fibrinolytic activity in vein walls (FAV) was determined by a semi quantitative fibrin slide technique in a group of 68 healthy middle-aged women consisting of 22 healthy controls, 19 non-smoking contraceptive pill users and 27 cigarette-smoking non-users. Significantly decreased FAV was demonstrated in pill users because of high frequency of low values among women using combined oral contraceptives (OC) for more than 5 years. Significantly lower FAV was also recorded in smoking non-users, among whom low FAV values were found mainly in heavy smokers. However, no effect of OC usage for less than 5 years was observed, neither did smoking of less than 10 cigarettes daily influence FAV. Thus, the two well-known risk groups with respect to circulatory diseases, long-term contraceptive users and heavy smokers, included the vast majority of middle-aged women with impaired plasminogen activator activity. PMID- 3090852 TI - Plasminogen activator and fibrinogen/fibrin degradation products at conization of the uterine cervix. AB - In women undergoing conization of the uterine cervix, peripheral blood samples and blood samples from the cone cavity were obtained and analysed for their concentration of plasminogen activator of tissue type (t-PA) and of urokinase type (u-PA) and the concentration of fibrinogen/fibrin degradation products (FDP). A significant increase was found for t-PA (p less than 0.002) and u-PA (p less than 0.0002) as well as for FDP (p less than 0.002) in blood from the cone cavity compared with peripheral blood. The finding of increased liberation of plasminogen activators strengthens the rationale for administration of synthetic inhibitors of fibrinolysis to reduce the frequency of bleeding complications at conization. PMID- 3090853 TI - Postoperative dislocation: a risk factor for periprosthetic ectopic ossifications after total hip replacement. PMID- 3090854 TI - Bone tissue response to irradiation and treatment model of mandibular irradiation injury. An experimental and clinical study. AB - The present study was conducted on bone tissue responses to irradiation towards a treatment model of mandibular irradiation injury by comparing the results of experimental observations of irradiation effects on rabbit hind legs and rat mandibular bones (paper I, II and III) with clinical observations of irradiation effects on the human mandible (paper IV, V and VI). The main results of the study were as follows: Bone marrow haemorrhage, eosinophilia and incipient edema were encountered in the rabbit leg one day after a single irradiation dose. Edema and fibrosis were the salient features after five weeks, while both regenerative and fibrotic changes predominated eleven weeks after irradiation. The changes were the more extensive the greater the irradiation dose was. Empty lacunae as a sign of cell damage in cortical bone already appeared on the first day after irradiation; this effect reached its maximum when the dose was 20 Gy or more. Bone marrow and subcutaneous tissue pO2 and pCO2 were measured by means of implanted Silastic tonometers in irradiated and nonirradiated rabbit hind legs. Single dose irradiation was followed by a rapid, dose dependent decrease of marrow pO2. The corresponding effect on pCO2 was weaker and appeared later. The response to hyperoxia in the bone marrow became weaker when the irradiation dose increased. Less significant was the response of CO2 tension to hyperoxia. O2 and CO2 tensions were recovered after single dose irradiation both in subcutaneous tissue and in bone marrow, but the reduction was less in bone marrow. During the twelve weeks observation period clearly better recovery in tissue gas tensions was observed in subcutaneous tissue than in bone marrow. Nonirradiated periosteal grafts on irradiated bone cavities in the rabbit tibia induced more rapid and intense mature bone formation than irradiated periosteal grafts. The irradiated periosteum, even after a single dose of 20 Gy, had some osteogenetic capacity. The alkaline phosphatase content was lowered eight weeks after surgery in irradiated legs but clearly exceeded control values twelve weeks after surgery indicating new bone formation. Lysosomal enzyme DAP II contents were increased in all irradiated specimens as a sign of disturbed bone formation. The tissue concentrations of acid phosphatase, cytochrome oxidase, lactate dehydrogenase, isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase and succinate dehydrogenase in the immediate postirradiation period showed a greater increase in activity in the cut lines of the irradiated rat mandibles than in those of the nonirradiated mandibles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3090855 TI - Antigenic and biochemical characteristics of Mobiluncus mulieris and Mobiluncus curtisii. AB - Twenty-four strains of Mobiluncus mulieris and 27 strains of Mobiluncus curtisii were tested with respect to 6 different biochemical characteristics: arginin decarboxylase activity, beta-galactosidase activity, synergistic hemolysis with Staphylococcus aureus, hydrolysis of hippurate, migration through soft agar and reduction of nitrate. Antigens of the same strains, prepared by ultrasonication, were subjected to sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by immunoblotting using polyclonal rabbit antisera against two of the M. mulieris strains and five of the M. curtisii strains. Two different strongly reacting protein antigens could be detected in the M. mulieris strains. These strains could be separated into three groups based on the possession of either of the two antigens or both. In the M. curtisii strains, 10 strongly reacting protein antigens could be detected. Four strains possessed only one of these antigens, one did not possess any, while the remaining strains possessed different sets of 9 of them. Within each species common protein antigens were detected. No antigens were found which were shared by both species. The biochemical characteristics studied could not differentiate between the antigenic groups in any of the species. None of the antigenic subgroups of M. curtisii found in the present study was identical with any of the two subspecies (curtisii and holmesii) which have been proposed. PMID- 3090856 TI - A comparison of different methods for determining elastase activity of Pseudomonas aeruginosa strains from mink. AB - We have characterized 20 Pseudomonas aeruginosa strains isolated from pneumonic mink lungs with regard to elastase production and serotype. P. aeruginosa PAO1, a well-characterized elastase-producing strain, and two elastase-deficient mutants of PAO1 were used for comparative purposes. Elastase activity was assayed on elastin agar and by using 14C-elastin coated microtiter plates. Elastase antigen was measured using a double antibody sandwich ELISA (enzyme-linked immunosorbent assay). Total proteolytic activity was determined on skim milk agar plates. The results from ELISA showed that all strains produced antigenically similar elastase, although the amounts produced varied considerably between strains. There was a good correlation regarding elastase assays between ELISA and 14C elastin, elastin agar and total proteolytic activity on skim milk agar. No correlation was found between serotype and elastase activity. The results showed that the 14C-elastin assay is a simple and sensitive method of determining elastolytic activity of P. aeruginosa strains. PMID- 3090857 TI - Susceptibility testing with disc diffusion for new cephalosporins: pre-diffusion revisited. AB - The purpose of the present study was to investigate the effect of 20-hour pre diffusion, i.e. placing the antibiotic-containing discs on the agar for 20 hours prior to inoculation, as compared to direct diffusion, i.e. placing the discs on the agar immediately after inoculation, for the newer 3. generation cephalosporins as represented by ceftazidime and ceftriaxone. Regression lines (zone sizes vs. inhibitory concentrations, as measured by plate-dilution) were constructed for three groups of bacteria chosen because of their differences in growth characteristics on agar: E. coli (n = 50), Enterobacter sp. (n = 35), and streptococci (n = 51). The results for both cephalosporins were: 20-hour pre diffusion produced larger zones than direct diffusion, regression studies for 20 hour pre-diffusion as compared to direct diffusion resulted in greater variation in zone sizes, numerically lower slopes, lower residual variances and higher correlation coefficients, and regression lines were significantly different for the 3 groups of bacteria with direct diffusion but not so with 20-hour pre diffusion. Considering the interpretation of zone sizes with disc diffusion for the cephalosporins tested, 20-hour pre-diffusion was superior to direct diffusion. PMID- 3090858 TI - Effects of carbon dioxide upon the in vitro activity of erythromycin. AB - The in vitro activity of erythromycin against clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae was examined by agar dilution and agar diffusion methods. The plates were incubated in air alone or in 8% CO2 and air. The minimal inhibitory concentrations (MICs) measured in air alone were lower for most of the isolates, compared to those found in 8% CO2. The greatest differences in MIC values were found for H. influenzae; the MIC 50% was 0.5 mg/l in air and 4 mg/l in 8% CO2. Sensitivity testing by the agar diffusion method (ICS) showed considerable differences between results obtained in air and in 8% CO2; the inhibition zones were generally smaller in CO2. The most marked reduction in zone sizes after incubation in 8% CO2 was seen with the H. influenzae isolates; 15 out of 43 isolates moved from the "sensitive" to "moderately sensitive" group. Sensitivity determination of aerobic bacteria for erythromycin should be performed in air alone in the routine laboratory. PMID- 3090859 TI - Interleukin 2- and interferon-production and expression of interleukin 2 receptors by human mononuclear cells stimulated with mumps virus or phytohaemagglutinin. AB - Interleukin 2 (IL 2) production, expression of IL 2-receptors and interferon (IFN) production in vitro by human mononuclear cells stimulated with inactivated mumps-virus antigen and phytohaemagglutinin (PHA, a T lymphocyte mitogen) were characterized. The detectable level of the T-cell lymphokine IL 2 in culture supernatants peaked after 18-24 hours for PHA stimulation and after 48 hours for mumps stimulation. The expression of IL 2 receptors was maximal on day 3 of PHA stimulation and days 5-6 of mumps stimulation. The IFN-level in culture supernatants showed only small variations during the culture period, both for mumps- and PHA-stimulated cultures, and IFN-gamma was detected in both cultures. PMID- 3090860 TI - Local disodium cromoglycate is ineffective in ulcerative proctosigmoiditis. AB - Conflicting results have emerged from studies using oral and rectal disodium cromoglycate (DSCG) in inflammatory bowel disease. In the present double-blind study, 43 patients with active ulcerative proctosigmoiditis received either placebo (n = 22) or 600 mg DSCG (n = 21) rectally as enemas for eight weeks. Assessment was made from clinical investigations, endoscopy, laboratory tests, biopsies, and diary cards. No statistically significant differences in bowel frequency, rectal bleeding, general well-being, abdominal pain, and severity and extent of the disease were found between the groups during the study. There was no significant change in the histologic parameters. No side-effect was encountered. It is concluded that DSCG did not improve symptoms or inflammatory changes in ulcerative proctosigmoiditis. PMID- 3090861 TI - Chemical regulation of the cerebral blood flow in cats with rostro- or prepontine transection of the brainstem. AB - Cerebral blood flow (CBF) and its response to hypercapnia were evaluated in cats with brainstem transected either at rostropontine (pretrigeminal preparation) or prepontine (cerveau isole preparation) level. Additionally, the effect of pentobarbital on CBF response to hypercapnia and to papaverine were examined. CBF was measured with 133 Xe intracarotid injection method. Cortical EEG activity was recorded. In rostropontine cats cerebral vessels responded with a dilatation to hypercapnia. In prepontine cats CBF response to CO2, was absent, where-as that to papaverine maintained. In rostropontine cats administration of pentobarbital, even in very low doses, caused disappearance of CBF response to hypercapnia, leaving that to papaverine. Our results support the idea that a neurogenic mechanism is involved in chemical regulation of CBF. The rostra1 part of the pontine reticular formation may be responsible for this neurogenic control. PMID- 3090862 TI - [Treatment of metastatic cancer of the prostate with LH-RH agonists]. PMID- 3090863 TI - [Lymphorrhea after retroperitoneal lymphadenectomy for testicular cancer]. PMID- 3090864 TI - Lithium compliance in alcoholic males: a six month followup study. AB - One hundred alcoholic patients were followed at monthly outpatient clinics for 6 months. Half were assigned low to moderate doses of lithium carbonate and half to chlordiazepoxide (10 mg tid) (active placebo). Drinking behavior and medication compliance were monitored at monthly clinics. After 6 months 52% of the lithium and 44% of the chlordiazepoxide patients were medication compliant. Of the 48% remaining in the lithium group, 14% did not return for a single visit while 14% came only once. Twenty percent came to clinic regularly; however they had never taken the medication as assigned. Of the 56% non-compliant chlordiazepoxide patients, 16% did not attend a single clinic; 24% came only once or twice and the remaining 16% attended clinics regularly although they were never medication compliant. Drinking days and the percentage of patients reporting abstinence for one or more months were determined for medication compliant patients and for patients who attended clinic regularly but who did not take medication. Data were analyzed by Kruskal-Wallis one way analysis of variance tests. While lithium and chlordiazepoxide compliant patients tended to report fewer mean drinking days per month (4.6 and 4.8 respectively) than the non-medication group (6.9) these differences were not significant; however, compared to 44% in the non-medication group, 60% of the lithium patients and 58% of the chlordiazepoxide patients reported having significantly more months of abstinence (p less than .05). These results do not show that lithium is differentially efficacious in reducing alcohol consumption. PMID- 3090865 TI - Glibenclamide induced prolonged hypoglycaemia. AB - Prolonged hypoglycaemia (serum glucose levels of 50 mg/dl and less, for more than 12 h in spite of treatment with periodic injections of hypertonic glucose) secondary to treatment with glibenclamide was found in 13 hospitalized patients. The mean daily dose of glibenclamide was 6.7 mg. In nine patients, the hypoglycaemia developed within 7 days of treatment. In two patients the tendency to hypoglycaemia lasted for more than 60 h in spite of continuous infusion of 5% or 10% glucose. Old age seems to be a crucial predisposing factor as none of the patients was under the age of 68 years. Contributing factors were renal failure and congestive heart disease. We feel that glibenclamide should be used with care in the elderly and in patients with renal or cardiac failure. PMID- 3090866 TI - Diagnostic value of lung uptake of indium-111 oxine-labeled white blood cells. AB - One hundred sixty-two white-blood-cell scans were retrospectively reviewed to determine the sensitivity and specificity of the test for pulmonary and pleural infection. All scans were performed 18-24 hr after injection of indium-111 oxine labeled autologous or donor cells. Pulmonary activity was graded on a scale of 0 4: 0 = equal to soft tissue; 1 = greater than soft tissue but less than rib; 2 = equal or greater than rib but less than liver; 3 = equal or greater than liver but less than spleen; 4 = equal to spleen. Activity was also characterized as being focal or diffuse. The white-blood-cell scan findings were correlated with the clinical diagnosis on the basis of physical examination, laboratory results, chest radiographs, clinical course, and pathologic studies when available. As pulmonary activity increased from grade 1 to 4, sensitivity declined from 93% to 14% and specificity increased from 64% to 100%. The sensitivity and specificity of focal uptake were 31% and 89% vs 62% and 74% for diffuse pulmonary activity. Making a distinction between focal and diffuse activity did not improve the specificity of low grades of pulmonary activity. The white-blood-cell scan can be very sensitive or very specific for pulmonary or pleural infection, depending on the criteria selected for a positive scan. PMID- 3090868 TI - Application of Program Evaluation and Review Technic (PERT) to laboratory research and development planning. AB - Software for the personal computer dramatically changes the ease with which managers of research and development can use network planning to guide projects to completion in the academic medical center setting. A case study of the use of the Critical Path Method (CPM) and Project Evaluation and Review Technic (PERT) in planning and implementing transcutaneous pCO2 monitoring by a department of laboratory medicine illustrates the utility and efficiency of these network planning technics. By means of iterative PERT analyses, the project was kept on track, despite an overly optimistic estimate of the completion date initially and intense demand by clinicians for use of the new monitoring technic in the management of premature infants with respiratory disease. Additionally, the iterative management approach improved project participants' expertise in estimating and meeting deadlines. Network planning is fully adaptable to the IBM PC or an equivalent microcomputer. This article summarizes several excellent project management software packages that have become available recently. PMID- 3090869 TI - Classification of protein-energy malnutrition in industrialized countries. PMID- 3090867 TI - Anatomy of congenital complete heart block and relation to maternal anti-Ro antibodies. AB - The anatomy of the conduction system was studied in 8 patients who had isolated congenital complete heart block. Atrial-axis discontinuity was seen in 7 hearts from children born to mothers with anti-Ro antibodies. The anticipated area of the atrioventricular node was occupied by fibrous and adipose tissue. The heart from the only child whose maternal serum was anti-Ro negative had nodoventricular discontinuity of the conduction system. This difference in anatomy may have etiologic significance. PMID- 3090870 TI - Survey on the management of febrile seizures. AB - A survey regarding the management of the child with febrile seizures was mailed to 10 000 child neurologists, neurologists, pediatricians, and family and general practitioners. The response rate varied by specialty; overall, slightly more than half the physicians responded. One third or less of physicians prescribed anticonvulsive therapy only at the time of febrile illness, although this practice was much less common among recent graduates. If children had lengthy or focal seizures, the majority of physicians in all specialties either prescribed long-term treatment or referred for consultation. Long-term daily anticonvulsant therapy was prescribed most frequently by child neurologists and least often by general practitioners, who most often referred for consultation. Rate of hospitalization also differed according to specialty. The results of the survey indicate that the management of a child with febrile seizures may differ depending on the specialty of the attending physician. PMID- 3090871 TI - Nutritional support of very-low-birth-weight infants requiring prolonged assisted ventilation. AB - We studied the influence of nutritional support on weight loss and time to regain birth weight (BW) (less than 1500 g) in infants requiring prolonged assisted ventilation. A total of 134 infants admitted between 1980 and 1982 were reviewed. Birth weight, gestational age, lowest recorded daily weight and percentage of loss, days to recover BW, energy intake, and nutrient source during the BW recovery period were determined. A decrease in weight loss (13% to 10%) and in mean (+/- SD) recovery time (20.9 +/- 7.3 days to 13.8 +/- 6.4 days) in very-low birth-weight, critically ill infants was noted. The use of parenteral feeding routes increased, as well as tolerance of initial enteral feedings following parenteral support. We attribute the decreased convalescence period for BW recovery to improved nutrition secondary to the increased use and earlier initiation of parenteral nutrition. PMID- 3090872 TI - When push comes to shove: a comparison between two methods of percutaneous endoscopic gastrostomy. AB - Percutaneous endoscopic gastrostomy has supplanted surgical gastrostomy in a number of medical centers. A variety of makeshift or commercially available gastrostomy kits has been used, as have several insertion techniques. Despite widespread use, however, there are conflicting reports regarding the best method of gastrostomy tube insertion. Studying 30 patients, 15 of whom underwent percutaneous endoscopic gastrostomy with the "push" and 15 with the "pull" technique, we found both methods successful, and associated with an acceptable complication rate. In the authors' hands, the "pull" technique was technically easier. PMID- 3090873 TI - Erythrocyte Rh antigens increase with red cell age. AB - Certain blood group antigens may play a role in the removal of senescent red cells from the circulation. In order to elucidate this hypothesis, we have investigated the effect of red cell aging on Rh blood group antigens. Red cells from volunteer donors were separated into subpopulations of uniformly defined densities on discontinuous Stractan density gradients. The number of the five major Rh antigen sites of each fraction was determined both by enzyme-linked immunosorbent assay (ELISA) and by hemagglutination-scoring technique. All Rh antigens tested increased with cell age (p less than 0.01). The data indicate that there is a positive correlation between red cell age and the Rh blood group antigen site number. PMID- 3090874 TI - Suppression of chemotactic activity of human polymorphonuclears by monoclonal IgMs with and without biological activity. AB - The influence of monoclonal IgMs on migration of human polymorphonuclears was studied at various temperatures by the use of 19 sera with monoclonal IgMs from patients with macroglobulinemia of Waldenstrom (MW) without obvious biological activity, 29 sera with monoclonal IgM cold agglutinins (18 with anti-I and 11 with anti-i IgMs) and 3 sera with monoclonal IgM rheumatoid factor (RF). Under agarose migration method and modified Boyden chamber method with double filters and 51Cr-PMNs were used. In under-agarose method, chemotactic differentials for controls, MW, anti-I, and anti-i groups were, respectively, 57 +/- 8 mm, 39 +/- 9 mm, 44 +/- 14 mm, and 32 +/- 16 mm at 37 degrees C and 47 +/- 18 mm, 22 +/- 11 mm, 17 +/- 9 mm, and 15 +/- 12 mm at 24 degrees C. All three sera with IgM RF inhibited chemotaxis. The differences between all groups and controls were significant at p less than 0.01. Random migration was inhibited at 24 degrees C (p less than 0.01) but not at 37 degrees C. Inhibitory concentrations of IgM in the sera tested were equal or less than 0.5 mg/ml. Thirteen sera were tested by the modified Boyden chamber method. At 37 degrees C 8 of 13 sera and at 24 degrees C 11 of 13 sera inhibited significantly chemotaxis at a concentration of IgM of 1 mg/ml. The lowest inhibitory concentration of IgM was 25 micrograms/ml. Eleven chromatographically pure IgMs were tested in the under-agarose assay. At concentrations of 0.4-3.7 mg/ml, eight IgMs inhibited chemotactic differential at 37 degrees C and nine inhibited it at 24 degrees C. At concentrations of 0.6-2.0 mg/ml, all seven pure IgMs tested by the Boyden chamber method significantly inhibited chemotaxis at 24 degrees C and 37 degrees C. Some IgMs inhibited chemotaxis at concentrations as low as 25 micrograms/ml. Ten IgM CA were eluted from the red blood cells. Eluates inhibited strongly chemotaxis at 24 degrees C and 37 degrees C. Heat inactivation did not alter inhibitory activity of IgM, however pepsin digestion or reduction and alkylation of purified IgMs did abolish their inhibitory activity. Inhibition of chemotaxis was not related to the light chain type, the titre, or the thermoamplitude of cold agglutination. However, monoclonal IgMs with anti-i cold agglutinin activity were stronger inhibitors than anti-I. Since 75% of IgMs tested inhibited chemotaxis at 37 degrees C, it is possible that monoclonal IgMs, especially those with anti-i cold agglutinin activity, inhibit PMN migration in vivo. PMID- 3090875 TI - Serum electrolyte patterns in end-stage renal disease. AB - The charts of 70 successive patients presenting for dialysis therapy for end stage renal disease (ESRD) were evaluated for their serum electrolyte values. The "classical" pattern of low total CO2 (tCO2), elevated anion gap ("delta"), and normal chloride was found in a minority of patients (14 of 70, or 20%). Hyperchloremia was noted in 46%; in 21 patients (30%), this was associated with a normal delta and in 11 (16%), hyperchloremia was accompanied by an elevated delta. Fourteen patients (20%), most with diabetic nephropathy, had normal serum electrolytes. Patients with chronic glomerulonephritis had a hyperchloremic pattern as often as not, and two of four patients with interstitial nephritis demonstrated hyperchloremia without an elevated delta. We conclude that the previously held thesis that hyperchloremia is a rare or absent finding by the time renal failure progresses to ESRD is no longer tenable. Furthermore, a significant minority of ESRD patients may require the initiation of dialysis at a time when their serum electrolytes are still normal. PMID- 3090876 TI - Infection in renal transplant recipients. Current approaches to diagnosis, therapy, and prevention. AB - Despite dramatic improvements in patient and renal allograft survival, infections continue to be an important cause of post-transplantation morbidity and mortality. Most serious infections manifest clinically as febrile diseases, and immunosuppression-induced compromised cell-mediated immunity is the basis for the predominance of infections due to opportunistic intracellular microorganisms. Diagnostic evaluation is guided by the timing of fever after transplantation, epidemiologic factors, and evidence of specific organ system involvement. Although current therapy of bacterial and parasitic infections is usually effective, the management of deep-seated fungal infections remains highly unsatisfactory. Cytomegalovirus disease, the single most important infection in some transplant centers, frequently presents as a self-limited viral syndrome; however, multiple organs may be affected. New measures for the rapid diagnosis and treatment of this viral infection hold promise. A number of recommendations have been proposed to prevent infections in renal transplant recipients; however, continued progress will depend primarily upon further refinements in immunosuppressive therapy. PMID- 3090877 TI - Infection in bone marrow transplant recipients. AB - Infection in marrow transplant recipients is determined primarily by the evolving immunologic milieu of each patient. Profound neutropenia and disruption of anatomic barriers are the most important risk factors for bacterial and fungal infections in the initial period after transplant. After this period, the occurrences of acute and then chronic graft-versus-host disease (GVHD) are the most important influences on the risk of infection. Major infections after the period of initial engraftment include viral infections (especially cytomegalovirus), fungal infections (due to Aspergillus and Candida), and rarely protozoal infections. GVHD appears to increase both the incidence and severity of cytomegalovirus infection. Bacterial infections also continue to occur, due predominantly to coagulase-negative Staphylococcus, as in the neutropenic period. Patients with chronic GVHD have continued abnormalities of host defenses, which may be further suppressed by treatment for GVHD. Major efforts have been directed toward preventing infection. In the neutropenic period, these include use of the protective environment, which has also been associated with a lower incidence of acute GVHD among patients who received transplants for aplastic anemia. The use of seronegative blood products is highly effective in preventing primary cytomegalovirus infection among seronegative patients. Among patients being treated for chronic GVHD, trimethoprim/sulfamethoxazole prophylaxis has been associated with a lower risk of infection. PMID- 3090878 TI - Infections in burn patients. AB - Systemic sepsis resulting from invasive infection remains the leading cause of death among patients hospitalized with major thermal injury. Prevention of infection and death in burn patients requires a thorough knowledge of the multiple predisposing factors involved and expert application of appropriate diagnostic, supportive, and therapeutic modalities. The improved survival in this population is a result of all these factors, not any one. It is this principle and the adherence to a treatment program that encompasses all the modalities which are so essential in the care of burn patients if continuing progress is to be made in this field. This article describes the current management of infection and infection control in burn patients. The burn wound and pulmonary system remain the major foci for infection in this population. Less common types of infection include suppurative thrombophlebitis, suppurative chondritis, bacterial endocarditis, urinary tract sepsis, sinusitis, intra-abdominal sepsis, and infections of the eyes. Prophylaxis protocols involve proper control of the environment and an anticipation of bacterial colonization. A number of specific monitoring and treatment guidelines have evolved that have proved effective over the years in minimizing morbidity and mortality. PMID- 3090879 TI - Significance of isolation of Aspergillus from the respiratory tract in diagnosis of invasive pulmonary aspergillosis. Results from a three-year prospective study. AB - The isolation of Aspergillus species from respiratory secretions has been regarded as being of limited usefulness in the antemortem diagnosis of invasive pulmonary aspergillosis. One hundred and eight consecutive patients were evaluated in whom Aspergillus species were isolated from respiratory secretions. Invasive aspergillosis was not demonstrated in non-immunosuppressed patients or in patients with solid tumors in the absence of neutropenia. Lung tissue was examined in 17 patients with leukemia and/or neutropenia; all had invasive aspergillosis. Tissue examination was not performed in 20 neutropenic patients; of 17 not receiving antifungal therapy, 16 died. Multivariate statistical analysis showed that neutropenia and absence of cigarette smoking were significant predictors of invasive aspergillosis in patients with respiratory tract cultures yielding Aspergillus. All cases of invasive aspergillosis were associated with A. fumigatus or A. flavus. The isolation of A. fumigatus or A. flavus from the respiratory tract of a patient with leukemia and/or neutropenia is highly predictive of invasive infection. Empiric amphotericin B therapy, without the necessity for tissue diagnosis, should be considered in this patient subgroup. PMID- 3090880 TI - Massive hemorrhagic myocardial infarction after coronary thrombolysis. AB - A 53-year-old man with occlusion of the proximal left anterior descending coronary artery received intravenous tissue plasminogen activator, and reperfusion was achieved within four and a half hours from the onset of chest pain. Recurrence of electrocardiographic ST segment elevation without attendant chest pain heralded reocclusion in the first hour after thrombolysis, which was successfully treated. After a stable course, post-infarction refractory cardiogenic shock developed on day 4, and autopsy demonstrated a massive (more than 100 cm2) hemorrhagic infarct. Several features of this case underscore the potential of coronary thrombolysis to cause significant reperfusion injury. PMID- 3090881 TI - Unusual case of central vein thrombosis and sepsis. AB - A patient with Crohn's disease who required placement of a right external jugular vein central catheter for total hyperalimentation is presented. Catheter-induced thrombosis and catheter-associated bacteremia and sepsis subsequently developed. Following the description of the case is a brief discussion of the complications inherent in central line placement, the mechanisms by which thrombosis and sepsis occur, and the measures that can be taken to decrease the incidence of thrombosis and sepsis in central line placement. The management of central venous thrombosis and sepsis is medical and not surgical in nature, and consists of catheter removal, antibiotics, and anticoagulation. PMID- 3090882 TI - Induction of subcutaneous and intraperitoneal abscesses in mice by Neisseria gonorrhoeae and Bacteroides species. AB - The pathogenicity in relation to encapsulation and potential for synergy between Neisseria gonorrhoeae and Bacteroides spp. was studied by subcutaneous and intraperitoneal inoculation of single organisms or mixtures of these organisms into mice. Ten isolates of N. gonorrhoeae and 12 isolates of Bacteroides spp. were studied. When injected alone, only heavily encapsulated organisms induced subcutaneous and intraperitoneal abscesses. However, N. gonorrhoeae did not induce intraperitoneal abscesses and did not survive in intraperitoneal abscesses even when inoculated with Bacteroides spp. Abscesses developed after subcutaneous inoculation of mixtures of heavily encapsulated Bacteroides and heavily or slightly encapsulated N. gonorrhoeae or of slightly encapsulated Bacteroides and heavily encapsulated N. gonorrhoeae. Heavily encapsulated N. gonorrhoeae did not survive in subcutaneous abscesses longer than 3 days after being inoculated alone and survived no longer than 7 days after inoculation with heavily encapsulated Bacteroides spp. An increase in the colony-forming units of Bacteroides spp. per abscess was observed when they were inoculated with N. gonorrhoeae. When mixed with heavily encapsulated isolates, slightly encapsulated N. gonorrhoeae or Bacteroides isolates became heavily encapsulated. These data demonstrate the effect of encapsulation on the relationship between N. gonorrhoeae and Bacteroides spp. and the potential for synergy between these organisms. PMID- 3090883 TI - Modification of maternal and fetal oxygenation with the use of tracheal gas infusion. AB - A new technique is described for producing changes in fetal blood gases in the chronically instrumented pregnant sheep. Gas mixtures were infused directly into the maternal trachea. Maternal and fetal carotid arterial blood gases and pH were measured. Air infusion at 16 L X min-1 produced no change. Oxygen infusion caused significant increases in maternal PaO2 at 2 L X min-1 and in fetal PaO2 at 4 L X min-1. Nitrogen infusion significantly decreased maternal anf fetal PaO2 at 4 L X min-1. During 4 L X min-1 oxygen infusion, maternal PaO2 rose rapidly to plateau at 314 +/- 47 mm Hg at 4 minutes and fetal PaO2 rose to plateau at 28.7 +/- 2.8 mm Hg after 7 to 8 minutes. Maternal PaO2 fell to 56.4 +/- 4.3 mm Hg during nitrogen infusion (4 L X min-1) while fetal PaO2 fell to 15.9 +/- 1.8 mm Hg. Continuous infusion for 5- to 6-hour periods produced a consistent rise in maternal PaO2 during oxygen infusion and a consistent decrease during nitrogen infusion. Tracheal infusion of gases can be used to change maternal and fetal PaO2 rapidly and predictably. PMID- 3090884 TI - Arterial PO2, PCO2, and pH versus transcutaneous PO2 and PCO2 and tissue pH in the fetal dog. AB - In the fetal dog, simultaneous recording by transcutaneous PO2 and PCO2 and tissue pH electrodes were compared to corresponding arterial values during hypoxic episodes produced by occlusion of the maternal abdominal aorta. Before occlusion, the differences between the paired values were minimal. Under anoxic conditions, expected changes in the peripheral circulation were observed. However, the transcutaneous PO2 was lower, the transcutaneous PCO2 much higher, and the tissue pH much lower than in blood. Continuous electrodes demonstrate changes resulting from gas and hydrogen ion coming from cells more readily than blood because they are closer to the former. Additionally, carbon dioxide and hydrogen ion are buffered to a greater degree in blood than in cells. Consequently, under conditions of stress and active metabolism, PCO2 is higher while PO2 and pH are lower in cells than in blood. When compared with monitoring of gases and acid-base balance through blood sampling, continuous transcutaneous and intracutaneous monitoring would seem to be more representative of the environment at the cellular level. PMID- 3090885 TI - Follicle-stimulating hormone and estrogen elevate deoxyribonucleic acid alpha nucleotidyltransferase activity in relationship to deoxyribonucleic acid synthesis in immature rat ovaries. AB - The deoxyribonucleic acid polymerase activities and deoxyribonucleic acid contents of ovaries were measured to clarify the relationship between hormone stimulated cell proliferation and the enzymes in ovaries of immature intact rats (4 to 29 days after birth) and hypophysectomized rats. The specific activity of deoxyribonucleic acid alpha-nucleotidyltransferase (the activity per microgram of deoxyribonucleic acid of the ovaries) drastically increased with an increase in the deoxyribonucleic acid content of the ovaries from 4 to 14 days after birth and then remained constant or slightly decreased after the increase, while the activity decreased gradually after hypophysectomy with no increase in the DNA content. Ovine follicle-stimulating hormone or estradiol-17 beta enhanced the deoxyribonucleic acid synthesis and alpha-nucleotidyltransferase activity in the ovaries of hypophysectomized rats, while deoxyribonucleic acid beta nucleotidyltransferase activity showed no significant change. Ovine luteinizing hormone, progesterone, and testosterone caused no significant increases. These results suggest that follicle-stimulating hormone or estrogen causes the induction of deoxyribonucleic acid alpha-nucleotidyltransferase accompanied by deoxyribonucleic acid synthesis in cell proliferation in immature rat ovaries. PMID- 3090886 TI - Contact lens-induced corneal endothelial polymegathism: functional significance and possible mechanisms. AB - The corneal endothelium is principally responsible for maintenance of corneal deturgescence. Therefore, compromise of corneal endothelial functional integrity can result in corneal swelling and opacification. Contact lenses constitute a potential insult to the cornea because their wear reduces the oxygen available to that tissue. It has been reported that contact lens wear induces transient as well as permanent morphologic changes in the corneal endothelium. One of the permanent changes reported is referred to as polymegathism, which is a variation in cell size within the endothelial monolayer. Several investigators have suggested that polymegathism reflects a compromised endothelial functional status. Mechanisms proposed to explain contact lens-induced polymegathism include lactate accumulation, changes in pH, and elevation in CO2 content. We discuss these possibilities as well as speculate that these polymegathous shape changes may be a result of decreased endothelial ATP (adenosine triphosphate) levels and disturbed calcium homeostasis due to corneal endothelial hypoxia. PMID- 3090887 TI - Ultrastructural morphometric analysis of Brucella abortus-infected trophoblasts in experimental placentitis. Bacterial replication occurs in rough endoplasmic reticulum. AB - Trophoblasts in normal and Brucella abortus-infected caprine placentas were examined by ultrastructural morphometric analysis to establish structural relationships of B abortus with cytoplasmic organelles; brucellae were identified with colloidal gold-labeled anti-B abortus bovine IgG. Cytotrophoblasts had large numbers of B abortus in cisternae of rough endoplasmic reticulum; binucleate trophoblasts did not contain bacteria. In infected trophoblasts there was a significant hypertrophy of B abortus-filled rough endoplasmic reticulum (RER) and a corresponding reduction in normal-appearing RER. Volume and surface density of RER in trophoblasts were: normal placentas (control), 2.8% and 0.30 sq mu; infected placentas, 27.9% (27.4% of which contained B abortus) and 0.56 sq mu (cells containing B abortus) and 3.3% and 0.34 sq mu (cells not containing B abortus). These data suggest that B abortus replicates within the RER of trophoblasts, possibly for synthesis and glycosylation of bacterial membrane proteins. PMID- 3090888 TI - Accumulation of arachidonate in triacylglycerols and unesterified fatty acids during ischemia and reflow in the isolated rat heart. Correlation with the loss of contractile function and the development of calcium overload. AB - Alterations in triacylglycerol and phospholipid metabolism are known to occur during the evolution of myocardial ischemic injury. The purpose of this study was to explore potential relationships between the accumulation of arachidonic acid and other fatty acids, the accumulation of triacylglycerol, and the progression of myocardial injury. Measurements of the fatty acid levels in triacylglycerol, unesterified fatty acids, and calcium content were correlated with myocardial function during ischemia and ischemia with reflow in an isolated perfused rat heart preparation. After 10 minutes of ischemia in this model, myocardial dysfunction was reversible, with recovery of left ventricular +dP/dt to 82.0% +/- 4.8% of control values upon reperfusion. Hearts did not recover with reperfusion after 30 minutes of ischemia and displayed a significant increase in tissue calcium content. A significant, nearly threefold increase in the arachidonic acid content of triacylglycerol was found after 10 minutes of ischemia and continued to increase with longer periods of ischemia and reflow. Other fatty acids also showed increased levels in triacylglycerol. The time course of accumulation of unesterified arachidonic acid paralleled the loss of myocardial function. Levels of free arachidonic acid were (in nanomoles per gram wet weight) 11.1 +/- 2.1 (SEM) for control hearts, 17.3 +/- 1.9 after 10 minutes of ischemia, and 38.4 +/- 2.5 after 30 minutes of ischemia. Increases in other free fatty acids contributed to a significant increase in total free fatty acid accumulation after 30 minutes of ischemia. Thus, the content of arachidonic and other fatty acids in triacylglycerol was found to increase early during ischemia, and a major increase in free arachidonic and other unesterified fatty acids occurred after a longer period of ischemia. These findings are consistent with an initial reincorporation of free fatty acids into triacylglycerol after release from membrane phospholipids, suggesting that membrane fatty acids may be a major source of triacylglycerol that accumulates in ischemic myocardium. In addition, these results suggest that a major increase in free fatty acids during ischemia and ischemia with reflow correlates temporally with the development of severe contractile dysfunction and accumulation of calcium in the heart. PMID- 3090889 TI - Chagas' disease in inbred III/J rabbits. PMID- 3090890 TI - The research agenda. PMID- 3090891 TI - Variations in enamel thickness and structure in East African hominids. AB - Tooth fragments are an appreciable but neglected proportion of fossil hominid specimens. The present study on 47 naturally fractured enamel surfaces of premolar and molar teeth of Plio-Pleistocene East African hominids measured enamel thickness, slope of incremental lines (striae of Retzius), and the morphology of Hunter Schreger bands (HSBs). Specimens allocated to three categories--"robust" australopithecines (EAFROB), "early Homo" (EAFHOM), and "unknown"--were photographed in ethanol with polarised light. Enamel thickness was measured on the occlusal (OT), cuspal (CT), and lateral (LT) aspects. The angle of intersection of striae of Retzius (D) with the enamel-dentine junction (EDJ) was recorded, together with the degree of curvature and width of Hunter Schreger bands (HSB). Absolute measurements of enamel thickness were scaled by using two allometry correction factors. Absolute thicknesses of all enamel measurements were significantly greater in the EAFROB (OT 3.1 mm; CT 3.3 mm; LT 2.4 mm) compared with EAFHOM (OT 1.4 mm; CT 1.6 mm; LT 1.6 mm) categories. Correction for size reduces the mean difference between the two taxa, but CT and OT thickness remain significantly different (P less than 0.05). HSBs in EAFROB were relatively straight and narrower (means = 52.8 micron) than in EAFHOM, which are more curved and wider (means = 62.0 micron), suggesting greater enamel prism decussation in early Homo. The slope of striae was less in EAFROB permanent molars (means = 23 degrees) compared with EAFHOM (means = 31 degrees), indicating faster rates of coverage during crown formation in "robust" australopithecines. We conclude that the study of fractured enamel surfaces can contribute to our understanding of the systematic relationships and patterns of enamel growth of early hominids. PMID- 3090892 TI - The first rib of hominoids. AB - Homo sapiens is unique among extant hominoids in displaying a univertebral articular pattern for the first rib; that is, the head of the first rib articulates only with the body of the first thoracic vertebra. All other hominoids, indeed virtually all other mammals, display a bivertebral pattern; that is, the head of the first rib articulates with the bodies of both the seventh cervical and the first thoracic vertebrae, as well as the intervening disk. Two fossil hominid partial first ribs, A.L. 288-lax and A.L. 333-118, show that the univertebral pattern was fully established in the hominid lineage by the appearance of Australopithecus afarensis. Four hypotheses, based in functional anatomy, can be postulated for the evolution of the univertebral pattern: (1), it increases the volume (via increased length) of the neck, which could, in turn, compensate for the functional loss of the laryngeal sac systems in hominid vocalization; (2), it is a consequence of the more barrel-shaped thorax in hominids; (3), it is a consequence of functional modifications in the hominid shoulder girdle; and/or (4), it is a consequence of modifications in hominid first rib motion while breathing in an upright stance. Fossil evidence supports all but the first hypothesis, and most strongly supports the third. However, evidence for the first hypothesis does suggest that the evolution of descent of the upper respiratory system in the hominid lineage may have been permitted by the presence of the univertebral pattern, while the reverse is probably not true. Furthermore, fossil evidence for the third hypothesis shows that, by the appearance of A. afarensis, the hominid upper limb had been freed from locomotor constraints, which concomitantly confirms full adaptation to upright posture. Thus, because of their potential relationship with upright posture, the two remaining hypotheses (i.e., "thoracic shape" and "first rib movement during breathing") also have support from the fossil evidence. PMID- 3090893 TI - A simple method for incorporating aequorin into mammalian cells. AB - A simple method for incorporating aequorin into mammalian cells to measure cytosolic ionized Ca2+ is described and compared with scrape loading and hypoosmotic treatment (HOST). The procedure consists of incubating the cells for 10 min and centrifuging them at 200 g for 30 s in the presence of aequorin. This method incorporates the same amount of photoprotein as scrape loading but 70% less than HOST. Cytosolic ionized Ca2+ has been measured in hepatocytes, kidney cells and tubules, macrophages, and cardiac myocytes loaded with aequorin by this new procedure. PMID- 3090894 TI - Effect of sulfonylureas on hepatic fatty acid oxidation. AB - In isolated rat livers perfused with oleic acid (0.1 mM), infusion of tolbutamide or glyburide decreased the rate of ketogenesis in a dose-dependent manner. The inhibition of fatty acid oxidation was maximal at 2.0 mM and 10 microM concentrations of tolbutamide and glyburide, respectively. Neither tolbutamide nor glyburide inhibited ketogenesis in livers perfused with octanoate. The inhibition of hepatic ketogenesis by sulfonylureas was independent of perfusate oleic acid concentration. Additionally, in rat livers perfused with oleic acid in the presence of L-(-)-carnitine (10 mM), submaximal concentrations of tolbutamide and glyburide did not inhibit hepatic ketogenesis. Finally, glyburide infusion into livers perfused with [U-14C]oleic acid (0.1 mM) increased the rate of 14C label incorporation into hepatic triglycerides by 2.5-fold. These data suggest that both tolbutamide and glyburide inhibit long-chain fatty acid oxidation by inhibiting the key regulatory enzyme, carnitine palmitoyltransferase I, most probably by competing with L-(-)-carnitine. PMID- 3090895 TI - Role of calcium in secretory and metabolic effects of substrates in the gastric mucosa. AB - The role of extracellular Ca2+ in the effects and oxidation of metabolic substrates was investigated in the isolated toad gastric mucosa. In the presence of lipoate, the stimulating effect of 10 mM glucose on spontaneous acid secretion was significantly reduced by 76% in Ca2+-free solutions. The inhibition was overcome by addition of 5 mM Ca2+. The increment in respiration induced by glucose was also blocked in the absence of external Ca2+. The effect of 10 mM pyruvate on acid secretion was inhibited by 37% in Ca2+-free solutions. The secretory responses induced by 10 mM butyrate and 10 mM octanoate were not significantly affected by Ca2+-free solutions. The rates of oxidation of [14C] glucose and [14C]pyruvate were significantly reduced by incubating in Ca2+-free solutions containing 0.1 mM of EGTA. When O2 uptake and glucose oxidation were measured simultaneously in the same preparation, the increment in the rate of glucose oxidation accounted for by 43% of the total increase of respiration observed in the presence of Ca2+. The rates of oxidation of [14C]butyrate and [14C]acetate were not significantly affected by Ca2+-free solutions. The rate of oxidation of [14C]glucose exhibited saturation kinetics versus concentration and was lower in the absence of external Ca2+ under a range of glucose concentrations. Similar results were observed when the experiments were performed in the absence of external potassium to block the acid secretory process. Ca2+ stimulated the rate of glucose oxidation in a dose-dependent manner. The kinetics of 45Ca2+ efflux and 45Ca2+ uptake were not significantly affected by glucose and butyrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090896 TI - Ornithine decarboxylase and mucosal growth in response to feeding. AB - The purpose of this study was to examine the role of ornithine decarboxylase (ODC) in the stimulation of the growth of gastrointestinal mucosa following feeding. Rats were divided into five groups: 1) fasted for 2 days, 2) fasted for 2 days and refed for 2 days, 3) fasted for 2 days and refed with the addition of 5% difluoromethylornithine (DFMO) to the drinking water, 4) normally fed, and 5) normally fed plus 5% DFMO in the drinking water. In general the results show a significant dissociation between ODC activity and growth of gastrointestinal mucosa in response to feeding. In the gastric mucosa, growth was inhibited by fasting and DFMO and stimulated by feeding, but there were no significant changes in ODC activity in any of the five groups. In the ileum ODC activity increased dramatically in refed rats and was essentially eliminated in rats fed DFMO. DFMO, however, had no effect on mucosal growth in fed rats and only prevented part of the trophic response to refeeding. The results in the colon were much the same as in the ileum, except that DFMO prevented even less of the trophic response to refeeding, despite total inhibition of ODC. These data suggest that polyamines necessary for growth of gastrointestinal mucosa following feeding are not supplied by the rapid activation of mucosal ornithine decarboxylase. PMID- 3090897 TI - Determination of prostaglandin E2 synthesis along rabbit nephron by enzyme immunoassay. AB - Prostaglandin E2 (PGE2) content and synthesis have been measured in microdissected segments from the entire nephron of rabbit kidney. PGE2 was determined by an enzyme immunoassay on glomeruli or tubular segments (0.5-5 mm) either immediately after microdissection (PGE2 content) or after incubation for 15 min at 37 degrees C in the presence of arachidonic acid (PGE2 synthesis). We confirmed that collagenase used for microdissection did not modify PGE2 synthesis. A linear correlation was found between the length of tubule used in the assay and PGE2 synthesis, as well as between incubation time with arachidonic acid and PGE2 synthesis. PGE2 synthesis, expressed in picograms per millimeter tubular length per 15 min, was maximum in medullary collecting duct (517 +/- 73). High values were also found in the granular portion of distal tubule (134 +/- 22) and granular or light portion of cortical collecting tubule (199 +/- 24 and 146 +/- 10, respectively). Synthesis was lower in all other segments: 17 +/- 6 and 24 +/- 12, respectively, in convoluted and straight proximal tubule, 67 +/- 12 and 71 +/- 5, respectively, in thin descending and ascending limb, 51 +/- 9 and 23 +/ 4, respectively, in medullary and cortical thick ascending limb of Henle's loop, and 25 +/- 7 in initial distal tubule. Synthesis per glomerulus was 24 +/- 3. When the protein content of each nephron segment is taken into account, this profile was not modified, except for the thin limbs of the loop, which reached values per nanogram protein slightly higher than those of the cortical collecting tubule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090898 TI - Lesions of nucleus tractus solitarii globally impair cerebrovascular autoregulation. AB - We studied the effects of acute bilateral electrolytic lesions of the nucleus tractus solitarii (NTS) on regional cerebral blood flow (rCBF) and its autoregulation in rats anesthetized (alpha-chloralose, 40 mg/kg), paralyzed (tubocurarine), and artificially ventilated. rCBF or regional cerebral glucose utilization (rCGU) was measured 30 min after NTS lesions, by the 14C iodoantipyrine technique or 2-deoxyglucose method, respectively. Cerebrovascular autoregulation was assessed in groups of 4-5 rats at three levels of arterial pressure (AP): 90, 125, and 140 mmHg. AP was lowered by hemorrhage or elevated by intravenous infusion of phenylephrine. NTS lesions did not alter rCBF at 125 mmHg (P greater than 0.05) but resulted in loss of autoregulation (P less than 0.05, analysis of variance). In contrast, lesions of the cuneate nucleus or transection of the baroreceptor afferents did not alter autoregulation. NTS lesions did not affect the reactivity of the cerebrovascular bed to hypercarbia (PaCO2 57.4 +/- 1; n = 5) or hypocarbia (PaCO2 24.4 +/- 1; n = 5) nor the rCGU in any brain regions (P greater than 0.05; n = 5). We conclude that lesions of the NTS impair cerebrovascular autoregulation. The effect is not due to changes in metabolism, nonspecific effects of the lesions, vasoparalysis, or interruption of the baroreceptor reflex arch. Neural pathways originating in or passing through the NTS can regulate the cerebrovascular autoregulation of the entire brain. PMID- 3090899 TI - Growth and hepatic composition in the guinea pig after long-term parenteral hyperalimentation. AB - This study examined the feasibility of maintaining male Hartley guinea pigs on long-term hyperalimentation. Data from animals fed ad libitum, but infused with 0.9% saline, indicated that there was minimal effect from catheter implantation, sepsis, or the infusion of large volumes of fluid. This group compared with animals fed and watered ad libitum demonstrated a nearly identical growth rate (6.33 +/- 1.18 and 6.12 +/- 1.32 g/day, respectively), serum chemistry, tissue weights, and hepatic composition and morphology. Animals infused with a total parenteral diet demonstrated growth rates of 4.06 +/- 1.46 g/day for up to 25 days. Loss of infused animals was due in varying degrees to sepsis, mechanical failure, improper placement of the cannula, loss of patency, and death from unknown causes. Morphological analysis of animals fed by total parenteral nutrition revealed an altered distribution and increased size of lipid droplets in hepatic parenchymal and Kupffer cells and glycogen accumulation by the parenchymal cells. Decreased hepatic content of total protein and lipid, as well as cytochrome P450, was also observed. Similarly, serum values of triglyceride were decreased in animals fed by the total parenteral diet. This study indicated that the guinea pig fed by hyperalimentation may be a useful animal model for a number of clinical and basic research applications. PMID- 3090900 TI - Fetal cardiovascular and endocrine responses to prolonged fetal hemorrhage. AB - Twelve chronically catheterized fetal sheep averaging 131 +/- 1 (SE) days gestation (term = 145-150 days) were hemorrhaged an average of 30.8 +/- 1.8% of their initial blood volume over 2 h by removing blood at 10-min intervals. During the hemorrhage, fetal blood volume decreased by 14.3 +/- 1.4%, and arterial pressure (AP), venous pressure (VP), and heart rate (HR) did not change significantly, although fetal plasma renin activity (PRA), arginine vasopressin (AVP), and norepinephrine (NE) were elevated to 1.5-2.5 times their initial values (P less than 0.05). Circulating levels of PRA, AVP, and NE began to rise when 5-10, 10-15, and 20-30%, respectively, of the initial blood volume was removed. Three to five hours after the hemorrhage, blood volume had returned to normal, AP was reduced by an average of 6 mmHg, VP was unchanged, and HR was elevated by an average of 20 beat/min; PRA, AVP, and NE averaged two to three times control (P less than 0.05). Twenty-two hours after the hemorrhage, blood volume was 5.4 +/- 2.4% above control; AP and HR returned toward normal; VP was elevated by an average of 2 mmHg; PRA and NE levels remained elevated (P less than 0.05), but AVP was not different from control. Plasma concentrations of epinephrine, dopamine, and prolactin showed little change during or after the hemorrhage. Thus these studies indicate that the fetus rapidly returns its blood volume to normal after a substantial loss of blood. In addition, the fetal cardiovascular and endocrine responses to a prolonged fetal hemorrhage of moderate volume are substantially less than those that occur after rapid hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090902 TI - [Bacterial flora of the gastric juice and bronchial secretion in the long-term respiratory intensive care patient]. PMID- 3090901 TI - Effects of 6-hydroxydopamine on brain catecholamines and on acute actions of ethanol in LS/Ibg and SS/Ibg mice. AB - LS/Ibg (LS) and SS/Ibg (SS) mice differ in ethanol-induced duration of loss of righting response or sleep time, hypothermia, hyperglycemia, and blood ethanol concentrations at regaining righting response. These differences in response to ethanol are a result of differences in central nervous system sensitivity and are mediated by polygenic systems. Studies have indicated that catecholaminergic systems may be involved in the differential effects of ethanol in LS and SS lines of mice (Masserano JM, Weiner N: Investigations into the neurochemical mechanisms mediating differences in ethanol sensitivity in two lines of mice. J Pharmacol Exp Ther 221:404-408, 1982). In this study the neurotoxin, 6-hydroxydopamine (6 OHDA), intracerebroventricular, was used to test this hypothesis. Administration of 6-OHDA markedly altered thermoregulation in LS mice but produced little effect in SS mice, and ethanol-induced hyperglycemia was attenuated in both LS and SS mice by 6-OHDA. Ethanol-induced sleep time was increased in SS mice pretreated with 100 micrograms of 6-OHDA, intracerebroventricular, whereas this response in LS mice was unaffected by 6-OHDA administration. Changes in sleep time were not related to changes in blood ethanol concentrations, indicating that 6-OHDA alters ethanol-induced sleep time by mechanisms other than brain sensitivity. Levels of norepinephrine and dopamine were determined in three brain regions, and the altered capacities for thermoregulation and glucoregulation were associated with changes in hypothalamic catecholamine levels. PMID- 3090905 TI - Generalized grand mal seizure after recovery from uncomplicated fentanyl etomidate anesthesia. PMID- 3090903 TI - Peroxisomes in human foetal kidney: variations in size and number during development. AB - The kidneys of 15 human foetuses (10-18 weeks of age) were used for morphometric studies on peroxisomes during gestational development and in organ culture. The catalase positive organelles revealed by DAB were round to ovoid with a granular matrix delimited by a membrane occasionally deformed by marginal plates. Generally, the distribution was uniform in cells of proximal tubules. In the same cell, size and density varied. The number fluctuated from cell to cell. No significant difference in the mean diameter was observed from the 10th to 18th weeks of gestation, although the mean value (0.36 +/- 0.1 micron) was significantly less than the adult figure. These results indicate that size modifications might occur later on in gestation or after birth to reach the adult value. During the studied period, the mean number of peroxisomes per 100 micron2 of surface area did not differ significantly from that of the 10-12 week group (10.5 +/- 1.97). No important changes of peroxisome morphology in kidney explants cultured for 7 days were noticed on day 3-4. Thereafter, the shape of many peroxisomes became elongated or irregular; marginal plates were frequent. A decrease in the diameter of peroxisomes began at day 4, became significant on day 5 and more accentuated on day 7. In addition, as the culture matured, there was a progressive reduction in catalase activity, revealed by a diminished density of the peroxisomal matrix. The number of DAB positive organelles per surface area decreased steadily with culture age, and significantly on day 2 (p less than 0.01) to become drastically low on day 5 and negligible on day 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090904 TI - Risk of transmission of sexually transmitted diseases by cryopreserved semen. AB - The increasing incidence of sexually transmitted diseases (STD) involves the risk of the transmission of these diseases by the artificial insemination. Therefore the cryotolerance of several microorganisms causing STD and the efficiency of penicillin of the cryoprotective medium (CMP) against Neisseria gonorrhoeae (N.g.) were investigated. The results have shown that penicillinase-producing N.g. (PPNG), genital mycoplasmas and Candida species survive the cryopreservation. Trichomonas vaginalis could not be recultivated after our temperature-time-regimen of the cryopreserving process. CPM with penicillin was unable to prevent a transmission of penicillin-sensitive N.g. PMID- 3090906 TI - A comparison of nitroglycerin and nitroprusside for inducing hypotension in children: a double-blind study. AB - Intravenous nitroglycerin (NTG) and sodium nitroprusside (SNP) were compared as hypotensive agents in anesthetized children and adolescents. The drugs were studied in a prospective, randomized, double-blind fashion in 14 patients anesthetized with nitrous oxide: oxygen, morphine, and thiopental. NTG in doses as high as 40 micrograms X kg-1 X min-1 was ineffective at decreasing mean arterial pressure (MAP) below 55 mmHg or causing a decrease in MAP greater than one-third of baseline values. SNP was uniformly successful at inducing hypotension in all patients, including those patients in whom NTG failed. The dose of SNP required to induce hypotension was 6-8 micrograms X kg-1 X min-1. Both NTG and SNP decreased systemic vascular resistance, although SNP did so to a much greater degree than NTG (64% vs. 29%; P less than 0.01). Only SNP increased cardiac index significantly (2.27 +/- 0.35 to 4.44 +/- 1.36; P less than 0.003). Both drugs reflexly increased heart rate, necessitating the use of intravenous propranolol (range from 1 to 3 mg) in all patients. Both drugs produced small decreases in arterial oxygen tension and increases in the average alveolar arterial oxygen tension gradient (SNP, 44 +/- 13 vs. NTG, 41 +/- 6). SNP use was associated with a slight metabolic acidosis (pH = 7.38 +/- 0.01; base excess [BE] = -6 +/- 1). Neither drug produced any other untoward reaction. SNP appears to be the agent of choice for the reliable and sustained induction of deliberate hypotension in children and adolescents. PMID- 3090907 TI - Morphological and morphometric study of the alterations on young mouse parotid gland with subpatent Chagas' disease. AB - In the present study we describe the morphological and morphometric alterations induced by two Trypanosoma cruzi strains (strains Y and Bolivia) in the mouse parotid gland during the subpatent period of infection. The acinar cells of animals inoculated 27 d after birth showed reduced eosinophilia, greater chromatin condensation, reduced height, and basally dislocated nucleus. The area occupied by the acini was decreased (999.38 micron 2 to 546.76 micron 2) and the volume of the acinar cells was reduced (116.28 micron 3 to 63.28 micron 3). Reduced height (21.20 micron to 14.28 micron) and decreased nuclear volume (125.28 micron 3 to 77.28 micron 3) occurred in the striated ducts. In the excretory duct there was reduced nuclear volume (121.16 micron 3 to 76.14 micron 3) and decreased height of the epithelial cells (26.05 micron to 14.00 micron). The presence of lymphoplasmocyte infiltrates was also observed. The changes induced by the Bolivia strain were qualitatively similar to those induced by strain Y, but more severe in nature. The present results indicate that infection with T. cruzi induces delayed development of the mouse parotid gland during the subpatent phase. PMID- 3090908 TI - Ketotifen, disodium cromoglycate, and verapamil inhibit leukotriene activity: determination by tube leukocyte adherence inhibition assay. AB - Peripheral blood leukocytes (PBL) from asthmatic individuals lose their former ability to adhere to glass when incubated with leukotriene C4 (LTC4). A modified leukotriene-induced leukocyte adherence inhibition (LAI) assay was therefore used to study the ability of anti-asthmatic drugs to abrogate such activity. Ketotifen, disodium cromoglycate, Verapamil, and dimethpyridene, all at concentrations of 2 X 10(-6) M, were co-cultured with 2 X 10(-7) M LTC4 and their effect on the LTC4-induced LAI determined. Verapamil, Ketotifen, and disodium cromoglycate all inhibited the LTC4 activity while the H1 antagonist, dimethpyridene, did not. These results suggest that the beneficial effect of Verapamil, Ketotifen, and disodium cromoglycate in bronchial asthma is probably as calcium antagonists that cause the inhibition of leukotriene activity. PMID- 3090909 TI - Metabolic acidosis as a presenting feature in acute asthma. AB - Acid-base abnormalities in adults with acute asthma are highly variable. The major abnormalities have been attributed to changes in PaCO2 secondary to altered alveolar ventilation. Primary metabolic alterations have been thought to be rare in adults. The frequency of metabolic acidosis in acute asthma was reevaluated by way of a review of the medical records of 164 hospitalizations involving 109 adults. The hydrogen ion concentration varied widely and in 27 of 164 episodes (16.5%) the arterial pH was lower than expected for the measured PaCO2. We conclude that the presenting acid-base status of adults with acute asthma is highly variable and metabolic acidosis is not an infrequent finding. PMID- 3090910 TI - Handcuff entrapment. PMID- 3090911 TI - Comparison of the results of card, rivanol, complement-fixation, and milk ring tests with the isolation rate of Brucella abortus from cattle. AB - Specimens from 4,553 cows were examined by card, Rivanol, and complement-fixation (CF) tests and bacteriologic culture. A ring test was performed on milk from 1,003 of these cows. The isolation rate of Brucella abortus correlated directly with antibody titers, and the field strain predominated in adult-vaccinated cows when the Rivanol test titer was greater than + 100 and the CF test titer was greater than 4 + 40. The CF test had the best balance of sensitivity and specificity in adult-vaccinated cows. The false-negative rate for the Rivanol and CF tests was higher in nonadult-vaccinated cows. PMID- 3090912 TI - Osmolal and anion gaps in dogs with acute endotoxic shock. AB - Serum osmolalities, biochemical concentrations, osmolal and anion gaps, blood lactate concentrations, and acid base status were evaluated in anesthetized, healthy control dogs and in dogs with endotoxic shock. The osmolal gap was not affected by endotoxemia. Compared with control dogs, dogs with endotoxic shock had mildly, though insignificantly, increased anion gaps and significantly increased blood lactate concentrations. The anion gap in dogs with endotoxic shock was positively (r = 0.77) and significantly correlated with the blood lactate concentration. Therefore, the blood lactate concentration of a dog in endotoxic shock may be estimated by use of the equation: lactate = 0.27 (anion gap) - 1.46. Confidence limits for this estimation were calculated. Dogs with endotoxic shock developed a lactic acidosis and hyperchloremic metabolic acidosis, with hyperventilation. PMID- 3090914 TI - Antibody-based enzyme-linked immunosorbent assay for determination of immune complexes in clinical tuberculosis. AB - Immune complexes were isolated from sera of tuberculosis patients by precipitation with 2.5% polyethylene glycol. The precipitates were characterized by quantitative determination of different immunoglobulin classes by single radioimmunodiffusion, sodium dodecyl sulfate polyacrylamide gel electrophoresis for presence of serum components, Ouchterlony's double diffusion method for detection of complement components C3 and C4, and immuno-dot assay for detection of Mycobacterium tuberculosis antigens. The results showed that polyethylene glycol precipitates of patients' sera were indeed immune complexes, as they contained immunoglobulins, albumin, complement components, and mycobacterial antigens, whereas precipitates from control sera contained mainly albumin. The antibodies present in immune complexes were specific to M. tuberculosis antigen and showed no binding to Escherichia coli antigens. Immune complex levels, as determined by the ability to bind M. tuberculosis antigens in an enzyme-linked immunosorbent assay, were significantly higher in tuberculosis patients (n = 22) than in healthy control subjects (n = 18). Thus, immune complex level could be a useful parameter in the diagnosis of active tuberculosis. PMID- 3090913 TI - Toxic and protective constituents in pet foods. AB - An analytical survey of mutagens, nitrosamines, polychlorinated biphenyls, toxic elements, and gamma-emission, as well as the toxicologically protective constituents zinc, selenium, and vitamin C, in 48 pet foods was conducted. Aside from high concentrations of fluoride and iodide in some samples and the expectedly higher concentrations of mercury and selenium in certain cat foods containing fish, the samples were notably free of the other toxic constituents. Direct-acting and promutagens and nitrosamines were not detectable in any of the samples. gamma-Emission was very low in all of the foods. Polychlorinated biphenyls were only detected in one cat food. PMID- 3090915 TI - Lack of bacterial aerosols associated with heat and moisture exchangers. AB - Contaminated condensate might serve as a source for cross infection. Heat and moisture exchangers (HME) are devices that humidify inspired gases, which pass through a hygroscopic felt pad surrounded by a cellulose sponge housed in a plastic case. In our study, we used a Servo 150 HME in place of a cascade humidifier in mechanical ventilator circuits. We performed 2 studies to evaluate the microbiologic safety of the HME. First, 42 HMEs used by patients for 24 h were tested in the laboratory for contamination. To simulate patient/air exchange, the HMEs were connected to the Andersen Sampler (flow at 35 L/min x 20 min). Although the inner felt pad of the HMEs was contaminated in 74% of the units (31 of 42), only 4.8% (2 of 42) generated 1 to 2 bacteria/702 L of air. In a second study, HMEs contaminated with either Staphylococcus aureus or Pseudomonas aeruginosa (at 10(3), 10(5), or 10(8) organisms/ml) were connected to an Andersen Air Sampler to simulate a ventilator circuit. Bacterial aerosols were not generated, with the exception of 2 to 4 bacteria recovered after contamination with 10(8) bacteria. The HME can provide humidification for mechanically ventilated patients with little risk of generating respirable bacterial aerosols. PMID- 3090916 TI - Bronchoconstriction induced by distilled water. Sensitivity in asthmatics and relationship to exercise-induced bronchospasm. AB - We studied the ability of bronchial challenge with an ultrasonically produced, distilled water aerosol to detect airways hyperreactivity in asthmatics and also evaluated its relationship to exercise-induced bronchoconstriction. Fifteen asthmatics and 10 normal subjects inhaled, at room temperature, distilled water aerosol in increasing concentrations. On a separate day, each subject performed a standard methacholine challenge. On the third day, all asthmatics exercised on a treadmill for 6 min at 90% maximal heart rate while breathing room-temperature, dry air. Pulmonary mechanics (FEV1 and SGaw) were measured before and after each challenge. Seven of the asthmatics and all of the normal subjects did not react to challenge with distilled water. Distilled-water challenge caused a 20% decrease in FEV1 in only 53% (8 of the 15) asthmatics, whereas all of the asthmatics reacted to methacholine challenge with a 20% fall in FEV1. Thus, distilled water was not a sensitive challenge procedure for the detection of airways hyperreactivity in asthma and it cannot be used as a routine screening test. However, in the asthmatics, the response to distilled water challenge correlated significantly with the response to exercise (r = 0.81, p less than 0.001). Seven asthmatics were reactive to both exercise and water, 7 were reactive to neither exercise nor water, and 1 reacted to water but not to exercise. Cromolyn completely or partially blocked both distilled-water- and exercise-induced bronchospasm in the reactive asthmatics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090917 TI - Acid maltase deficiency in an adult. Evidence for improvement in respiratory function with high-protein dietary therapy. AB - Acid maltase deficiency (AMD) in the adult is associated with progressive ventilatory muscle weakness and death from respiratory failure, but effective therapy is not available at present. Because recent evidence suggests that muscle catabolism may contribute to muscle weakness in AMD, we treated a 55-yr-old man with AMD and severe ventilatory muscle weakness with a high-protein (1.6 g/kg), weight-reducing diet for 27 months. High-protein dietary therapy was associated with striking improvement in respiratory function, including measures of ventilatory muscle strength and endurance. We suggest that high-protein dietary therapy may be useful in adults with AMD and respiratory insufficiency. PMID- 3090918 TI - NIH workshop summary: Nutrition and the respiratory system. Chronic obstructive pulmonary disease (COPD). PMID- 3090919 TI - Supplement on future research in tuberculosis. Prospects and priorities for elimination. Endorsement of the American Thoracic Society Board of Directors in March 1986. PMID- 3090921 TI - Growth-hormone-releasing hormone: a clinical update. PMID- 3090920 TI - Indications for arterial blood gas analysis. AB - Arterial blood gas analysis is used to evaluate oxygen and carbon dioxide gas exchange and acid-base status. Few studies identify indications for arterial blood gas analysis, especially with regard to optimizing the quality of patient care. General indications in severely ill adults usually include pathophysiologic abnormalities that can alter gas exchange or acid-base disturbances. Most commonly identified general indications have not been prospectively studied to determine if this analysis is necessary for diagnosis or management. Clinical settings where analysis is indicated involve patients with acute asthma in the emergency room, postoperative treatment of patients who have had coronary artery bypass graft surgery, stable patients in the intensive care unit, and patients receiving prophylactic supplemental low-flow oxygen by nasal cannula. Advances in noninvasive monitoring have suggested other possible clinical settings. However, further prospective, controlled clinical studies are needed to establish indications for arterial blood gas analysis and the role of noninvasive monitoring. PMID- 3090922 TI - Markers for non-A, non-B hepatitis. PMID- 3090923 TI - Manual for use of Montgomery laryngeal, tracheal, and esophageal prostheses. AB - This manual is designed to instruct the surgeon, nurse, and, directly or indirectly, the patient on the updated usage of prostheses involved with reconstructive surgery of the larynx, trachea, and esophagus. The silicone tracheal T-tube has been modified in an attempt to prevent its being displaced posteriorly into the trachea. The silicone tracheal cannula can be used in place of a tracheotomy tube unless there is aspiration or positive pressure breathing is required. Its success with sleep apnea has been especially gratifying. The salivary bypass tube and the esophageal tube continue to be of use when treating esophageal fistulas, strictures, and reconstruction of the cervical esophagus. The laryngeal keel and stent are described and illustrated for use with reconstructive laryngeal surgery. PMID- 3090924 TI - Blood-brain-barrier disruption interventional neuroradiology in brain tumor therapy. PMID- 3090925 TI - [Hemodynamic repercussions and clinical tolerance of 6 class I anti-arrhythmia agents in acute myocardial infarction]. AB - Clinical safety and hemodynamic repercussions were studied after administration of six class I antiarrhythmics (xylocaine, ajmaline, mexiletine, lorcainide, indecainide and tocainide) to patients presenting acute myocardial infarction without complications. The hemodynamic parameters monitored generally followed the same trends. A significant decrease of more than 10 per cent of the initial value was seen in systolic blood flow after injection of lorcainide, indecainide and tocainide. Peripheral vascular resistance increased moderately. Pulmonary capillary pressure increased by more than 40 per cent of the starting value after administration of mexiletine, indecainide and tocainide (significant increase in case of mexiletine). These changes in patients presenting infarction without complications are not of clinical importance. There were, however, two very severe cases of hemodynamic reaction after administration of mexiletine. Other signs of intolerance were seen, but they were of minor importance and administration of the drugs was not interrupted. Xylocaine and ajmaline produced the smallest depression of left ventricular functional activity in these patients. PMID- 3090926 TI - Qualitative differences in effects of recombinant alpha-, beta- and gamma interferons on human peripheral blood leukocytes in vitro. AB - The in vitro effects of bacteria-produced human interferons alpha 2, beta and gamma on several properties of peripheral blood leukocytes from different healthy donors were compared. Treatment with HuIFN-alpha 2 or HuIFN-beta resulted in inhibition of the proliferative response to phytohaemagglutinin and in closely parallel induction of 2'-5'-oligoadenylate synthetase activity. In contrast, HuIFN-gamma had no significant effect on these two activities. However, all three HuIFN were able to enhance natural killer cell cytotoxicity and the expression of HLA-DR surface antigens, with only quantitative variations from donor to donor. Similar results were observed with glycosylated recombinant hamster-cell-derived HuIFN-gamma and with natural HuIFN-gamma. These data demonstrate qualitative differences in the effects of HuIFN-gamma compared to those of HuIFN-alpha 2 or beta on cells of the immune system. PMID- 3090927 TI - Quantitation of intercellular binding strength by disruptive centrifugation: application to the analysis of adhesive interactions between P815 tumour cells and activated macrophages. AB - The cell binding assay described in the present paper provides a quantitative measurement of intercellular binding strengths between P815 mastocytoma cells and macrophages activated for cytotoxicity. Conjugates were submitted to a dislodgement force generated by centrifugation tending to remove radiolabelled probe cells from macrophages adhering to a glass support. Non-specific binding occurred between P815 cells and the glass support, but was negligible on siliconed coverslips. The adhesive interactions macrophage/glass were strong enough to resist up to about 1 X 10(-9) N, the maximal dislodgement force tested. Completion of conjugate formation was reached at 37 degrees C after 45 to 60 min and was inhibited at 4 degrees C or in Ca++-free medium. The strengths of intercellular bonds between P815 cells and macrophages varied from 7 X 10(-11) N (the minimal force applied) to more than 9 X 10(-10) N. No clear-cut separation between weak and strong interactions was observed when the centrifugation step was performed at 4 degrees C. In contrast, when centrifugation was carried out at 37 degrees C, a subpopulation of loosely bound tumour targets could be distinguished from more strongly bound P815 cells. PMID- 3090928 TI - Macrophage activation: some questions. PMID- 3090929 TI - A novel approach for improving the efficacy of experimental cancer chemotherapy using combinations of anticancer drugs and L-histidinol. AB - One of the major limitations to the chemical management of human malignancies is the failure of most antineoplastic agents to act specifically against tumour cells. A novel approach for improving both the specificity and the efficacy of experimental cancer chemotherapy is described in this review. The approach is based upon the use of L-histidinol in combination with conventional anticancer drugs. L-Histidinol, a structural analogue of the essential amino acid L histidine, is a reversible inhibitor of protein biosynthesis which evokes disparate responses from non-tumorigenic and tumorigenic cells in culture. Whereas L-histidinol protects a wide variety of phenotypically normal cells from anticancer drug toxicity, it enhances the vulnerability of tumorigenic cells to the same agents. More importantly, these remarkable properties of L-histidinol are retained in tumour-bearing animals. Thus, L-histidinol diminishes the myelocytoxicity otherwise associated with the in vivo use of agents such as cytosine arabinoside and 5-fluorouracil. Simultaneously, L-histidinol increases the inherent capacities of these two antimetabolites to eradicate in situ tumour cells. More recently, it has been found that L-histidinol can increase both the specificity and the efficacy of a number of other antineoplastic agents. For example, alkylating agents such as BCNU, cyclophosphamide and cis-platinum, as well as the antitumour antibiotic daunomycin, can be combined with L-histidinol to provide curative treatment for tumour-bearing animals under conditions where these drugs, on their own, have little or no impact on survival. These results demonstrate that the L-histidinol/anticancer drug combination approach to chemotherapy is effective with a variety of clinically-relevant antineoplastic agents. However, it remains to be demonstrated whether this approach will prove applicable in, or effective for, human cancer chemotherapy. PMID- 3090930 TI - Free kappa light chains in multiple sclerosis spinal fluid. AB - Based on prior reports of free light chains of immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS), we quantitated free kappa and lambda chains and whole IgG concentrations using sensitive and specific radioimmunoassays (RIAs). The RIA for free kappa chains had a sensitivity of 0.25 micrograms/ml and was capable of specifically measuring free kappa chains in whole CSF or serum even in the presence of a 4-log excess of whole IgG. By RIA, free kappa chains were detected in CSF samples from 33 (84%) of 39 MS patients but in only 1 (2.4%) of 42 controls. The control patients included 10 with noninfectious inflammatory diseases and 9 with central nervous system infections. The concentration of free kappa chains in the CSF of the MS patients was 1.40 +/- 1.21 micrograms/ml. Free kappa chains were concentrated in the CSF 71- to 120-fold relative to reference proteins. In contrast, increased levels of free lambda chains or of whole IgG were nonspecific; abnormalities were seen in controls with infections or inflammatory diseases as often as in MS patients. These studies suggest that the measurement of free kappa light chains may have important diagnostic usefulness, since the specificity of the finding for MS appears to be high. PMID- 3090931 TI - A cupful of luck, a pinch of sagacity. PMID- 3090932 TI - Beta-amino acids: mammalian metabolism and utility as alpha-amino acid analogues. PMID- 3090933 TI - The assessment of fluctuating odontometric asymmetry from incomplete hominid fossil data. AB - Problems of small sample size and incompleteness of fossil data in the evaluation of metric asymmetry may be overcome by the application of cluster sampling techniques together with factorial analyses of variance. Degrees of fluctuating odontometric asymmetry are reported in Australopithecus, Homo erectus and Homo neanderthalensis. In all three populations mesiodistal dimensions were shown to be more asymmetric than buccolingual dimensions, with maxillary teeth exhibiting significantly greater degrees of asymmetry than mandibular teeth. Neanderthal teeth were significantly more metrically asymmetric than those of either Australopithecus or H. erectus, with population differences in asymmetry centered in the maxillary teeth. PMID- 3090935 TI - International symposium on the emerging epidemic of meningococcal disease in N.W. Europe. Amsterdam, The Netherlands, 6 and 7 May 1985. Abstracts. PMID- 3090934 TI - [Antibiotic resistance of clinical strains of Pseudomonas aeruginosa from various O-serogroups]. AB - The results of the study on antibiotic resistance of 745 strains of P. aeruginosa isolated in hospitals from surgical patients, environment and carriers are presented. 89.7 per cent of the strains were typed by the commercial O-sera. The isolates were most sensitive to tobramycin (99 per cent), amikacin (95.1 per cent), cefsulodin (95.1 per cent), polymyxin (89.7 per cent) and gentamicin (73.5 per cent). Comparison of the antibiotic resistance of the typed and nontyped cultures revealed that the former were more resistant to tetracycline, carbenicillin, rifampicin, kanamycin and cefotaxim, while the latter were more resistant to gentamicin and polymyxin. It was also noted that the proportion of the strains resistant to all of the tested antibiotics was higher among the nontyped cultures. Antibiotic sensitivity of P. aeruginosa was in many respects defined by the strain origin: the strains isolated from patients were more resistant to tetracycline, carbenicillin, rifampicin, cefotaxim and kanamycin and more sensitive to gentamicin and polymyxin than the strains isolated from the environment. The cultures belonging to different O-serogroups (O-11 and O-2) markedly differed by their antibioticograms. PMID- 3090936 TI - Light-induced increases in the glycine decarboxylase multienzyme complex from pea leaf mitochondria. AB - The rates of mitochondrial glycine oxidation estimated by CO2-release and glycine bicarbonate exchange activities in fully greened tissues are approximately 10 times greater than those of etiolated pea leaves and potato tuber mitochondria. The release of CO2 from glycine in intact mitochondria isolated from dark-grown and nonphotosynthetic tissues was sensitive to inhibitors of mitochondrial electron transport, glycine transport, and glycine decarboxylase activities. The CO2-release and glycine-bicarbonate exchange activities in crude mitochondrial protein extracts from light-grown versus dark-grown tissues exhibited light/dark ratios of 12 and 21, respectively. This suggests that the differences in capacity to oxidize glycine reside with the glycine decarboxylase enzyme complex itself. The complex is composed of four subunit enzymes, the P, H, T, and L proteins, which can be isolated individually and reconstituted into the active enzyme. The activities of P and T proteins were at least 10 times higher in fully greened pea leaves than in the etiolated tissue, while the H and L protein activities were four times higher in these same tissues. The levels of P and T proteins detected immunochemically were substantially lower in total mitochondrial extracts prepared from leaves of dark-grown pea seedlings. Labeling of whole pea seedlings and in vitro protein synthesis with isolated mitochondria indicated that the entire glycine decarboxylase enzyme complex is cytoplasmically synthesized and therefore encoded by the nucleus. Polypeptides synthesized from total leaf polyadenylated mRNA isolated from leaves of both the dark-grown and light-treated peas indicated the presence of P protein. This implies that translatable messages for this enzyme are present at some level throughout leaf development. PMID- 3090937 TI - The conformation of monkey pituitary somatotropin. AB - Monkey pituitary somatotropin has been studied by zero-order, second-order, and circular dichroism spectroscopy. Difference absorption spectra have also been generated during proteolytic digestion of the hormone. The molar extinction coefficient of the native protein was found to be 23,800 +/- 550 (M-1 cm-1) at 276.6 nm. A comparison of the conformations of monkey and human pituitary somatotropins indicates a close relationship between the two molecules, including alpha-helix contents of 55 +/- 5%. PMID- 3090938 TI - Functional linkage between phycobilisome and reaction center in two phycobilisome oxygen-evolving photosystem II preparations isolated from the thermophilic cyanobacterium Synechococcus sp. AB - Photosystem II oxygen-evolving preparations with attached phycobilisomes were isolated from the thermophilic cyanobacterium Synechococcus sp. with beta octylglucoside or digitonin. Fluorescence emission spectra of the two preparations determined at 77 K largely lacked a far red band which originates from photosystem I. The spectrum of the digitonin preparation was otherwise similar to that of intact cells, whereas the beta-octylglucoside preparation showed a pronounced band at 687 nm, which is considered to be emitted from phycobilisomes. The relative yield of phycobilin fluorescence was similar between the digitonin preparations and the cells but was considerably larger in the beta octylglucoside preparations at room temperature. The quantum yield of ferricyanide photoreduction determined with light which is absorbed mainly by phycobiliproteins was 0.85 for the digitonin preparation and 0.57 for the beta octylglucoside preparation. The results indicate that excitation energy is transferred from phycobilisomes to photosystem II reaction centers in the digitonin preparation as efficiently as in intact cells, while a significant portion of light energy harvested by phycobilisomes is not utilized by the primary photochemistry in the beta-octylglucoside preparation. Digitonin and beta octylglucoside preparations had 65 and 48 chlorophyll a molecules per photosystem II reaction center, respectively. The beta-octylglucoside preparation contained twice as much phycocyanin and allophycocyanin per photosystem II reaction center as the digitonin preparation, which has a phycobiliprotein-to-photosystem II reaction center ratio very similar to that of cells. It is concluded that whereas the beta-octylglucoside preparation contains a considerable amount of free phycobilisomes, all phycobilisomes present in the digitonin preparation are physically and functionally linked to photosystem II reaction center complexes. PMID- 3090939 TI - [Clinical study of PSK as an adjuvant immunochemotherapeutic agent against gastric cancer]. AB - The effects of PSK in combination with Mitomycin C, Adriamycin and Tegafur were studied in 168 patients who underwent gastrectomy for gastric cancer. The study group receiving PSK showed improved survival and there was a significant difference in the estimated survival. An improved survival rate was also shown at stages III and IV, in the group given an FAM regimen and in the group with well differentiated adenocarcinoma. PMID- 3090940 TI - [5-FU concentration in the blood and tissue of patients with gastric and colorectal cancer after administration of UFT or tegafur]. AB - UFT or tegafur (5, 7.5 and 15 mg/kg, respectively) were given to Donryu rats with AH-130 cancer twice a day for 3 days, and 5-FU concentrations in the blood, tumor, normal stomach and large bowel tissues were measured by chemical assay and compared. The 5-FU concentrations in the tumor were higher than those of normal tissues and still remained 12 hours after the final dosage. According to increased UFT dosage, there were significantly higher levels of 5-FU concentration in tumor tissues but blood levels of 5-FU were low. The peak of concentration occurred at one to two hours after the final dosage. However, increase in tegafur dosage volume did not correlate with 5-FU levels. Clinical cases (74 patients) of gastric and colorectal cancer were orally administered UFT or tegafur at 300 mg twice a day for 3 days preoperatively. Materials were obtained at surgery at 5.5 hours on average after the final dosage and 5-FU levels in tissues were measured by chemical assay. Concentrations of 5-FU in cancerous tissues after UFT administration were 0.177 +/- 0.131 micrograms/g in gastric cancer and 0.130 +/- 0.051 micrograms/g in colorectal cancer, while in patients to whom tegafur had been administered, the concentrations were 0.194 +/- 0.124 micrograms/g and 0.119 +/- 0.075 micrograms/g, respectively. There was no significant difference in 5-FU levels between the UFT-administered group and the tegafur group. PMID- 3090941 TI - [Effects of krestin (PSK) on drug-metabolizing enzymes with special reference to the activation of FT-207]. AB - The effects of PSK on hepatic drug-metabolizing enzymes were investigated using Sarcoma 180-bearing and non-tumor-bearing ICR mice. PSK, an immunomodulator, has been commonly used in combination with tegafur for post-operative adjuvant chemotherapy. Tegafur is a typical masked compound transformed into 5-FU by the hepatic drug-metabolizing enzyme P-450. It has been reported that immunostimulants such as BCG and anaerobic Corynebacterium suppress the drug metabolism. PSK and Propionibacterium acnes were administered to mice inoculated s.c. with Sarcoma 180. It was demonstrated that Propionibacterium acnes had an effect of inhibiting these enzymatic activities, especially the amount of P-450 and cytochrome b5 and aminopyrine demethylation. On the other hand, PSK had no influence on the drug-metabolizing enzymes. Propionibacterium acnes was shown to decrease the 5-FU level in organs and sera of mice given FT-207 orally. By contrast, PSK showed no difference in 5-FU level compared to controls, indicating that PSK had no inhibitory effect on the activation of FT-207 by hepatic drug metabolizing enzymes. PMID- 3090942 TI - [Complete remission in a case of concurrent breast and thyroid cancers with metastatic spinal paralysis]. AB - A case of right breast and thyroid cancer is reported in which, despite metastasis to the spinal cord occurring 1 year after mastectomy, satisfactory therapeutic results were obtained. At the time of her first examination the patient had spastic paresis involving all segmental levels below Th7. Bone scintigraphy disclosed multiple hot areas in the spinal column, centering around Th5 6. On myelography, complete block was noted above the lower margins of the vertebral body of Th5. The paresis progressed to result in a complete loss of touch and pain sensations with flaccid paralysis of both lower extremities. Laminectomy of Th4-6 was therefore performed on the 20th day of hospitalization. Biopsy at that time demonstrated the metastasis to be from the breast cancer. Radiotherapy (Linac, 600 rad/w) was started at the 20th postoperative day, a total dose of 3,000 rad being given. Physicotherapy was instituted simultaneously. As drug therapy, OK-432 and FT-207 suppositories (750 mg) were used in addition to diethylstilbestrol, 300 mg/day. RESULTS: After 6 months of these combined therapeutic regimens the patient became capable of moving along the edge of the bed with the aid of a good hand and leg. After 7 months she underwent radical surgery for the thyroid cancer and 3 months later she was discharged asymptomatic. PMID- 3090944 TI - Toads and psoriasis. PMID- 3090943 TI - Selective decrease of 15-hydroxyeicosatetraenoic acid (15-HETE) formation in uninvolved psoriatic dermis. AB - Epidermis of psoriatic skin lesions is characterized by elevated 5-lipoxygenase and 12-lipoxygenase products. 15-hydroxyeicosatetraenoic acid (15-HETE), the predominant lipoxygenase product in normal dermis, has the potential to inhibit 5 lipoxygenase and 12-lipoxygenase. The purpose of the present study was to determine the capacity of homogenized dermis from uninvolved psoriatic skin to form 15-HETE in vitro. Extracted lipids were separated by reversed-phase high performance liquid chromatography. Each chromatographic peak was identified by its coelution with authentic standards, by ultraviolet spectrometry, and by radioimmunoassay. Dermis from uninvolved psoriatic skin generated on average 48% less 15-HETE than normal dermis (P less than .01). In contrast, the formation of 12-hydroxyeicosatetraenoic acid was increased by 56% in psoriatic dermis (P less than .01). Prostaglandin E2 formation was similar in normal and psoriatic dermis. Since 15-HETE can inhibit the synthesis of 5-lipoxygenase and 12-lipoxygenase products that possess inflammatory and proliferative capacities, a defective 15 HETE generation in dermis may be of importance for the development of psoriasis. PMID- 3090945 TI - Histologic responses of port-wine stains treated by argon, carbon dioxide, and tunable dye lasers. A preliminary report. AB - Although the blue-green argon laser light has been used successfully to treat port-wine stains (PWSs) for many years, it produces substantial epidermal damage. We have previously shown in normal human skin that pulsed yellow tunable dye lasers (577-nm wavelength) can cause highly selective damage to cutaneous microvessels with minimal injury to the overlying epidermis. Pulsed tunable dye lasers also produce selective vascular injury in the abnormal vessels of PWSs, with clinically apparent lightening of the lesions. Both epidermal injury and fibrosis are less severe with this laser treatment than with argon and carbon dioxide laser treatments. Clinical and histologic responses of PWSs treated by argon, CO2, and pulsed yellow dye lasers were compared and followed up for one month in three patients. Although larger and longer-term clinical trials are necessary to fully evaluate this new treatment modality, it appears that pulsed yellow laser radiation offers a more selective, less traumatic, and probably superior form of treatment for PWSs. PMID- 3090946 TI - Transcutaneous estimation of arterial carbon dioxide in intensive care. Which electrode temperature? AB - Transcutaneous and arterial carbon dioxide were measured simultaneously in 57 children (age range 10 days to 14.3 years) undergoing intensive care. All were haemodynamically stable at the time of study. Mean calibration time with 5 and 10% carbon dioxide was 43 (range 38-58) minutes and mean arterialisation time was 10.5 (range 3-30) minutes. Duplicate hourly arterial samples over a four hour period showed that transcutaneous: arterial carbon dioxide correlation was independent of electrode temperatures over the range 42-44 degrees C and was independent of child age. One and a half hours after electrode placement transcutaneous carbon dioxide (kPa) = arterial carbon dioxide X 1.41 + 0.02. Use of a simple ratio (arterial carbon dioxide = transcutaneous carbon dioxide/1.40) resulted in a mean estimate of arterial carbon dioxide within 3% of the actual value with coefficients of variation of 11 and 15% at 1.5 and 4.5 hours, respectively. For prediction of arterial carbon dioxide 95% confidence limits around the regression mean rose from +/- 1.04 kPa (7.8 mm Hg) at 1.5 hours to +/- 1.56 (11.7 mm Hg) at 4.5 hours. Baseline drift was more than +/- 0.67 kPa (5 mm Hg) during 22% of the studies. For a drift of less than 0.67 kPa 95% confidence limits were 0.87 and 1.12 kPa, respectively. Arterial carbon dioxide can be estimated with clinically acceptable tolerances from surface electrodes operating at temperatures between 42-44 degrees C. Improved electrode stability and speed of calibration should make this a valuable monitoring technique. PMID- 3090948 TI - Nutritional treatment of congenital heart disease. AB - Twelve of 13 patients with congenital heart disease given continuous enteral nutrition displayed normal growth; cardiac function remained stable or improved in 10 in spite of the water load (146 +/- 22 ml/kg/day). This is safe treatment for malnutrition in congenital heart disease. PMID- 3090947 TI - Restricted feeding and human intestinal plasma cell development. AB - Small intestinal mucosa from 129 necropsies and 15 surgical specimens from infants aged from birth to 21 months was examined for the presence of cells containing IgA, IgM, and IgG using the PAP immunoperoxidase technique. Immunoglobulin containing cells were nearly always absent in infants under 1 week of age but occurred in the second week of life in infants who had had milk feeds. At this time, IgM containing cells were predominant, but IgA containing cells were more numerous by the sixth week. IgG containing cells were generally sparse. Parenterally fed infants who had received little or no intestinal milk showed significantly fewer immunoglobulin containing cells than those who had been fed normally, irrespective of gestation. Lack of stimulation by food and bacterial antigens may contribute to immunoglobulin containing cells failing to occur in these parenterally fed neonates. PMID- 3090949 TI - Modulation of granulocyte oxidative response by recombinant interferon alpha 2 and gamma. AB - Interferon (IFN) has been described to influence various cellular functions. In this study we investigated whether the oxidative response of polymorphonuclear leukocytes (PMN) is also affected by IFN. In order to exclude the possible influence of impurities in IFN preparations, only recombinant human IFN alpha 2 or gamma were used. Lucigenin-dependent chemiluminescence (CL) of PMN was measured to assess the production of oxygen radicals. IFN gamma at a concentration of more than 10 ng/ml elicited a minimal CL response in PMN. When PMN were incubated with IFN gamma for 1 h and then stimulated with chemotactic peptide f-met-phe (FMP), zymosan-activated serum (ZAS), zymosan particles, or phorbol-myristate acetate (PMA), the CL response was increased as consequence of the generally enhanced oxidative metabolism. IFN alpha 2 showed no such effect at any concentration tested. A 5-min pretreatment with IFN gamma decreased the ZAS response but did not affect the reaction to the other stimuli. The possibility of a generation of IFN by PMN during the assay could be excluded as no IFN activity could be detected in an antiviral assay after stimulation of PMN for 6 h with PolyI X PolyC, LPS, ConA, C. parvum, PMA, zymosan, or FMP. The modulation of granulocyte activity by IFN gamma may be important in the regulation of the anti inflammatory response of PMN. PMID- 3090951 TI - Assessment of primary vs. secondary toxicity of Aroclor 1254 to mink. PMID- 3090950 TI - Polychlorobiphenyl congeners, p,p'-DDE, and sperm function in humans. PMID- 3090953 TI - [Effect of hydralazine on the formation of malondialdehyde in platelet-rich plasma and aortic rings in the rat]. PMID- 3090952 TI - [Importance of calcium in the interaction between prostaglandins E and sulfonylureas in utero]. PMID- 3090955 TI - Quantitative evaluation of Leydig cells in testicular biopsies of men with varicocele. AB - A quantitative analysis of Leydig cells was performed in 23 testicular biopsies of men with left varicocele and sperm count ranging from zero to 95,000 sperm/mm3. The oligozoospermic patients had more Leydig cells and higher FSH and LH serum levels than the patient group with more than 10,000 sperm/mm3. The Leydig cell density appeared tightly correlated (p less than 0.01) with the serum level of LH. In oligozoospermic subjects, an altered Leydig cell function could trigger an increased LH secretion; this seems likely to be responsible for the stimulation of interstitial cells resulting in an exaggerated recruitment of mature Leydig cells from their precursors. The comparative analysis of left and right testes failed to show differences in Leydig cell density and spermatogenesis in normozoospermic and oligozoospermic patients. This suggests that the two testes are equally involved by a possible, although unknown, detrimental effect of left side varicocele. PMID- 3090954 TI - A randomized trial for the study of the elective surgical treatment of portal hypertension in mansonic schistosomiasis. AB - From 1977 to 1983, 94 patients with esophageal varices and gastrointestinal bleeding secondary to mansonic schistosomiasis were entered into a prospective randomized trial comparing the three operations mainly used in Brazil: esophagogastric devascularization associated with splenectomy (EGDS, 32 patients), classical splenorenal shunt (SRS, 32 patients), and distal splenorenal shunt (DSRS, 30 patients). The randomization was interrupted because of a significant incidence of portosystemic encephalopathy (PSE) in the SRS group (26%), as compared to the DSRS (7%) and EGDS (0%) groups. The rate of rebleeding was the same in the three groups, but the rate of failure, as defined by the presence of technical problems, postoperative complications, or death, was significantly higher in the SRS group. This 2-year follow-up shows that SRS should be abandoned in hepatosplenic schistosomiasis and that a comparison between DSRS and EGDS with a longer follow-up is urgently needed. PMID- 3090957 TI - [Current treatment of cancer of the esophagus in our department]. PMID- 3090956 TI - Effects of Ramadhan fast on male fertility. AB - Ramadhan fast did not have any adverse effect on the fertility of healthy men. In fact there were some suggestions that fasting improves the total sperm count, the gonadotrophic hormone levels, and the testosterone level in fertile males. Fasting does not either improve or decrease the seminal quality of azoospermics but may have some effect on oligozoospermics. There was a beneficial effect of the Ramadhan fast on spermatogenesis, either via the hypothalamo-pituitary testicular axis or by a direct effect on the testis. PMID- 3090958 TI - [Coronary revascularization at the acute phase of myocardial infarction. Short and median-term survival of 359 patients. Multicenter study]. AB - Three hundred and fifty nine consecutive patients from 4 different French centres who underwent attempted early coronary revascularisation during the acute phase of myocardial infarction by intracoronary thrombolysis (309 cases) intravenous thrombolysis (26 cases) and transluminal angioplasty (24 cases) were reviewed to evaluate the short and medium term results of these non-surgical techniques. Three groups of patients were identified from the results of initial and secondary coronary angiography: 1) deaths during the procedure (1.9%), 2) successes, with immediate and stable revascularisation (65%), 3) failures, also including initial successes with secondary reocclusion (33.1%). The global mortality at one month was 10.9%. This was significantly lower after revascularisation (p less than 0.001): 4.7% in patients with successful procedures and 17.6% in the others. The one year survival rate was also significantly higher in patients successful revascularisation (93 +/- 4% vs 75 +/ 8%, p less than 0.001). There were more recurrent infarctions and residual angina in patients with successful early coronary revascularisation: 7.7% and 12% respectively vs 4.2% and 8.4% respectively in the other patient group. In the successful group, 200 patients (86%) had one or more stenoses greater than 70% narrowing after coronary revascularisation. The recurrent infarction rate in the 94 patients treated medically was 9% and 17% had residual angina compared to 6% and 10% respectively in the 106 patients referred for coronary bypass surgery or undergoing complementary angioplasty. Three conclusions may be drawn from this non-randomised study of coronary revascularisation during the acute phase of myocardial infarction: attempts at coronary revascularisation do not aggravate the immediate prognosis of myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090959 TI - [Intravenous streptokinase versus heparin in recent acute myocardial infarction. Randomized multicenter study in the Franche-Comte]. AB - A multicentre randomised therapeutic trial was undertaken in 8 hospitals in the Franche-Comte department of France (Belfort, Besancon, Dole, Lons-le-Saunier, Luxeuil, Montbeliard, Vesoul, Pontarlier) in which 101 patients with acute primary myocardial infarction were treated within 5 hours of onset of symptoms with either intravenous streptokinase (1,500,000 U in 30 mn) or conventional heparin therapy. The results were assessed on the clinical outcome, arterial patency in the necrosed territory and global and regional ejection fractions (EF) at the 3rd week. After randomisation, 51 patients were given heparin and 50 received streptokinase. Seven patients died in the heparin group and 4 in the streptokinase group (NS). At the third week, the artery in the necrosed zone was patent in 69% of the heparin group and in 68% of the streptokinase group (NS). The EF was significantly higher in the patients with patent arteries in the necrosed zone than in those with occluded arteries (0.49 +/- 0.12 vs 0.41 +/- 0.15, p less than 0.01). There was no significant difference in EF between the heparin and streptokinase groups. The EF was significantly higher in patients with anterior infarction who received streptokinase than in those who received heparin (0.40 +/- 0.10 vs 0.33 +/- 0.09 p less than 0.05). Segmental wall motion was significantly better at the apex and free wall. There was no significant difference between the two groups in posterior infarction. These results show that reestablishment or maintenance of arterial patency in the necrosed zone improves left ventricular function and that patients with anterior wall infarction are the ones most likely to benefit from streptokinase therapy. PMID- 3090960 TI - [Mitral valve prolapse and pectus excavatum. Expressions of connective tissue dystrophy?]. AB - Pectus excavatum is a common malformation in diseases of elastic tissue (Marfan, Ehlers-Danlos...). When observed apparently alone it may represent a minor form of dystrophy, implying the same risk of a cardiac lesion. Abnormalities of the thoracic skeleton and echocardiographic mitral valve prolapse is a well established association, suggesting a common disorder of connective tissue. However, there is no absolute proof that this is a statistically significant association. Histological connective tissue changes relating these two markers have yet to be found. Clinical and echocardiographic examinations and skin biopsies were performed in 17 patients with pectus excavatum. Mitral valve prolapse was detected in 65% of cases (associated in 1 out of 3 cases with tricuspid valve prolapse). In 53% of cases electron microscopy showed abnormal skin collagen and elastin. Collagen abnormalities were twice as common as those of elastin and could be associated. Mixed changes of thinning of elastin and collagen fibres of irregular calibre were particularly suggestive. Pectus excavatum would therefore seem to be the expression of a minor form of dystrophy of collagen and elastin tissues and a clinical marker of possible mitral valve prolapse. PMID- 3090961 TI - [Treatment of acute pulmonary embolism with urokinase compared with the combination plasminogen-urokinase. Apropos of 67 cases]. AB - Sixty-seven patients with recent acute pulmonary embolism (within 5 days) and an angiographic deficit of over 30% were included in a randomised study designed to compare the efficacy of the associations of urokinase-heparin (Group I) and lysyl plasminogen-urokinase-heparin (Group II). Plasminogen was administered as an intravenous bolus of 150 microkatal units at the beginning of the urokinase infusion, the dosage of which was set at 2 700 000 IU over 24 hours. Both groups received anticoagulant doses of heparin. The efficacy of treatment was judged by early revascularisation on pulmonary angiography performed during the 24 hours after the end of treatment and by changes in the parameters of fibrinolysis and its inhibitors. The clinical features of the two groups were comparable but the angiographic changes were more pronounced in Group I (deficit: 68.5 +/- 10.4% vs 62.3 +/- 10.9%, p less than 0.02). Treatment had to be stopped before the 24th hour in 4 cases (3 early deaths and 1 severe haemorrhage). The average revascularisation was 30.5 +/- 6.8% in Group I and 38.3 +/- 31.1% in Group II (NS). The alpha-2-antiplasmins were lower (NS) in Group II as were the fibrinogen levels (p less than 0.01 at the 12th and 24th hour) whilst the plasminogen levels and surface of fibrin plateaux were higher (p less than 0.01 at the 6th hour and p less than 0.05 at the 12th hour, respectively). These results show that moderate doses of urokinase associated with heparin are effective in the treatment of acute pulmonary embolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090962 TI - [Hemodynamic course during fibrinolysis in severe pulmonary embolism]. AB - Seventy seven cases of severe pulmonary embolism (Miller index greater than 13 points) including 61 acute (under 5 days) and 16 subacute episodes, underwent continuous haemodynamic monitoring during treatment with either urokinase 2 000 U/kg/h for 24 hours with heparin (Group I: 18 patients), or urokinase 4 500 U/kg/h for 12 hours without heparin (Group II: 47 patients), or with streptokinase 2 00 000 U over 10 hours (Group III: 12 patients). Efficacy was defined as greater than 20% improvement of Miller index at control angiography after 48 hours (Group I: 10 patients, Group II: 31 patients, Group III: 8 patients). In the 49 patients (63%) with good results, the Miller index fell by about 50% with a significant increase in cardiac index (20%) from the 12th hour. There was a concomitant fall in pulmonary systolic arterial pressure (35%). In the 28 patients (37%) with partial improvement a 20% increase in cardiac index and an 18% fall in pulmonary systolic arterial pressure were observed only in the high dose urokinase group, despite incomplete pulmonary revascularisation demonstrating the vasodilator effect of this protocol. Fibrinolysis was repeated in the patients with incomplete results or a Miller index of over 13 points, leading to improvement in 78% of patients. Accelerated lysis of pulmonary embolism leads to rapid normalisation of haemodynamic parameters and improves the prognosis of massive pulmonary embolism by reducing the number of recurrences and the mortality rate (4%). PMID- 3090963 TI - [Nuclear magnetic resonance in the diagnosis of aortic diseases]. AB - The diagnostic value of nuclear magnetic resonance imaging was assessed in a number of aortic pathologies: aneurysms of the thoracic and abdominal aorta, sinus of Valsalva aneurysms and dissection of the aorta. The imager was equipped with a resistor magnet providing a field of 0.15 Tesla. An electrocardiographic gating system was perfected. The images obtained were very satisfactory as they provided three dimensional morphological information and a qualitative assessment of blood flow. Further studies are now required with comparison with other invasive and non-invasive diagnostic methods to determine the clinical role of NMR imaging and to evaluate the diagnostic sensitivity and specificity of this new technique. PMID- 3090964 TI - [Thromboses of the right atrium: echocardiographic aspects, practical management. Apropos of 8 cases]. AB - Right atrial (RA) thrombosis is rare. The aim of this study was to determine their clinical and echocardiographic features and therapeutic implications. In the last 7 years, 16 RA masses were detected by 2D echocardiography. The diagnosis of thrombosis was made in 8 cases based on anatomo-pathological examination (6 cases) or their disappearance with medical treatment (2 cases). The clinical presentations were: pulmonary embolism (4 cases), anterior myocardial infarction (2 cases), Ebstein's anomaly (1 case), thrombosis of a Leveen catheter (1 case). Only 1 patient had atrial fibrillation. Two echocardiographic appearances were observed: 1) a long, very mobile thrombus floating between the RA and right ventricle (4 cases), 2) a relatively immobile mass (4 cases). The 4 patients with relatively immobile thrombi survived: 2 underwent surgery and 2 were treated medically. All cases of floating thrombi had pulmonary embolism: 2 patients underwent surgery but the postoperative course was complicated; 2 patients died suddenly before surgery. These cases show that 2D echo is the diagnostic method of choice for detection of RA thrombosis. The floating RA thrombus is a therapeutic emergency and has a poor prognosis. PMID- 3090965 TI - [Pulsed and continuous Doppler in qualitative and quantitative diagnosis of mitral insufficiency]. AB - The aim of this study was to assess the diagnostic value of pulsed and continuous wave Doppler in mitral regurgitation. One hundred and twenty-one patients (64 women and 57 men aged 13 to 76 years, average 54 years) investigated for mitral regurgitation or ischaemic heart disease underwent left ventricular angiography and continuous wave and pulsed Doppler echocardiography. In addition to clinical examination, they also underwent M mode, 2D echocardiography and phonocardiography. They were divided into two groups according to the presence or absence of mitral regurgitation on angiography, chosen as the reference method. Group I comprised 51 patients with angiographic regurgitation, and Group II 70 patients without mitral regurgitation. The sensitivity of the Doppler examination was 98%. Of the 51 patients in Group I there was only one false negative in a patient with doubtful angiographic regurgitation in the context of an endocardial cushion defect. In comparison, the sensitivity of clinical examination and phonocardiography were 74.5% and 80% respectively; 13 cases of mitral regurgitation on angiography and Doppler echocardiography had no auscultatory signs. The specificity of the Doppler examination was 92.8%; 5 of the 70 patients in Group II had unquestionable systolic turbulence in the left atrium and 2D echocardiography showed the possible mechanism of these valvular leaks in 3 cases: 1 bivalvular prolapse, 1 rheumatic valvular thickening and 1 papillary muscle dysfunction. We interpret these 5 cases as being true mitral regurgitation but intermittent or too slight to be visible on angiography. The positive predictive value of systolic turbulence in the left was 90.9% and the negative predictive value was 98.4%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090966 TI - [Endocarditis on cardiac pacemaker endocavitary electrodes. Apropos of 7 cases]. AB - The authors report 7 cases of endocarditis on cardiac pacing catheters observed out of a total of 2 950 primary implantations and 1 600 pacemaker replacements. This is a rare condition (0.15%) but carries a poor prognosis as it usually occurs in elderly patients and demands aggressive management. The presence of multiple pacing catheters and surgical contamination due to manipulation of the pulse generator (reimplantation, pacemaker replacement) are predisposing factors. The infecting organism in these cases was a staphylococcus. One case of metastatic infection was also observed (acinetobacter). Ablation of the septic endocarditic material under effective, prolonged, double antibiotherapy is essential. Recently implanted electrodes were withdrawn by simple traction in 2 cases. This manoeuvre was attempted initially in all cases but stopped when chest pain or runs of ventricular extrasystoles occurred. Open heart explantation of pacing electrodes adherent to the ventricular apex was performed in 5 patients. Cardiopulmonary bypass without cardiac standstill enabled dissection of the fibrous rings surrounding the catheter after purging the blood from the atrial and ventricular cavities. In one patient, associated tricuspid valve endocarditis was found and valvular replacement was performed with a bioprosthesis. Endocardial pacing was replaced by epicardial pacing in patients with permanent AV block. The prognosis of this condition is poor; there were 2 deaths in this series of 7 patients. PMID- 3090967 TI - [Experimental induction of sino-auricular blocks on isolated atria. Microelectrode study of the effects of bepridil]. AB - The effects of bepridil on sinoatrial conduction were studied by perfusing 15 isolate rabbit right atrial preparations. In a preliminary series an increase in cycle length was observed with a dose-dependent effect with concentrations of between 5 X 10(-7) M and 1 X 10(-5) M. At the latter dose, sinoatrial block was observed. Bepridil was therefore used in a series of 10 preparations to induce sinoatrial block (SAB). After 10 minutes perfusion the cycle length increased significantly (14.3%, p less than 0.02). In 4 preparations SAB occurred 18.7 +/- 2.5 minutes after the onset of the perfusion. Sinoatrial block did not occur in 6 cases and in 4 cases an intrasinus shift of the dominant pacemaker was observed. The types of SAB observed were varied and their mechanisms were complex. Different types of SAB occurred in the same preparation. The different types of block recorded were: Blumberger type I SAB, anterograde 2/1 SAB, intrasinus 2/1 block, retrograde 2/1 and advanced block, complete atrio-sinusal dissociation. PMID- 3090968 TI - [Compressive hemopericardium of the right atrium after cardiac surgery]. AB - Between June 1983 and September 1984, 3 patients operated for mitral valve disease presented with acute right heart failure due to right atrial compression. Emergency echocardiography did not show pericardial separation around the ventricles but in the apical 4 chamber view severe right atrial compression by an extracardiac mass was observed. Emergency surgery was performed in all three cases to evacuate a localised haemopericardium despite the absence of pericardial fusion. These cases of acute right ventricular failure underline the importance of multiplying the number of echocardiographic views in order to detect localised pericardial effusion. The diagnosis should be made as soon as possible as clinical deterioration may be rapid despite effusions of small volume. The main differential diagnoses are right atrial thrombosis and acute postoperative pulmonary embolism. In these cases of localised tamponade, the clinical signs are the result of vena caval compression or extrinsic compression of the tricuspid orifice. The preferential localisation of the haemopericardium around the right atrium is difficult to explain. It is probably related to the low pressures in this region. The echocardiographic appearances of this condition have been established allowing reliable diagnosis. PMID- 3090969 TI - [Double mitral orifice. An anatomical case]. AB - A double mitral orifice was discovered at autopsy in a 74 year old woman. Death resulted after several episodes of cardiac failure complicating mixed mitral and aortic valve disease. A vertical limbus bridged the mitral annulus separating it into two distinct right and left orifices, with oblique long axes aligned towards the lower part of the limbus perpendicular to each other from the left atrial view. After opening the left ventricle, both orifices were observed to have their own sets of chordae tendinae attached to normal papillary muscles: the right orifice to the posterior and the left to the anterior papillary muscle. The inferior end of the limbus was attached to a supplementary papillary muscle. Echocardiography and CT scanning were performed before dissection. This malformation results from symphysis of the mid parts of the two mitral leaflets during embryonic stages 15 and 16 (8-10 mm vertex-coccyx, 31st-33rd days). PMID- 3090970 TI - [Tricuspid endocarditis with right-left shunt in the atrium]. AB - A case of tricuspid regurgitation due to endocarditis causing a right-to-left shunt through a patent foramen ovale is reported. Tricuspid valve endocarditis occurred after septic abortion and caused valvular regurgitation with dyspnea and cyanosis. The diagnosis was made by echocardiography and the finding of peripheral arterial desaturation, and it was confirmed at surgery. The physiopathology of these right-to-left shunts is the same as that already described during traumatic tricuspid regurgitation: reopening of the foramen ovale by the right atrial dilatation and ventricularisation of right atrial pressures. The presence of a shunt is an indication for surgery. PMID- 3090971 TI - [Congestive cardiomyopathy in addiction to clobenzorex, an anorexigenic drug]. AB - Cardiac failure caused by high doses of amphetamine-like drugs is rare. We report a case of decompensated congestive cardiomyopathy occurring in a 29 year old woman addicted to clobenzorex (Dinintel). This patient had been taking 5 to 7 capsules per day for 5 years. No other cause of cardiac failure was detected. A rapid improvement was obtained by digitalis and diuretic therapy; no further episodes of cardiac failure were observed after one year. However, the drug could not be completely withdrawn and echocardiography has shown increasing left ventricular dilatation. The possible mechanisms of amphetamine induced myocardial toxicity are discussed and the analogy with the group of adrenergic cardiomyopathies is underlined. PMID- 3090972 TI - [Ultrasonic association between false tendons and ventricular aneurysm. Apropos of 2 cases]. AB - The authors report 2 clinical cases of ventricular aneurysm associated with a false tendon attached to the neck of the aneurysm. The first patient had no signs of false tendon before myocardial infarction. When the aneurysm developed, a false tendon was observed at its neck; a second false tendon attached to the first was also seen and appeared to have ruptured. The second patient had a right ventricular aneurysm with the same appearances of false tendon. These two cases suggested that the formation of an aneurysm might project a common muscular band into the ventricular cavity giving electrocardiographic appearances of a false tendon. We observed this association in 6 out of 23 cases of ventricular aneurysms in a prospective study. It is important to recognise this phenomenon and to differentiate it from other echogenic structures (thrombus). PMID- 3090973 TI - [Traumatic aorto-right ventricular fistula. Apropos of a case]. AB - The authors report the case of a 19 year old young man with an aorto-right ventricular fistula caused by a stab wound. The diagnosis was not made initially during surgery to control haemorrhage (left hemothorax due to a damaged internal mammary artery). However, three weeks later, a continuous murmur was detected and the diagnosis established by echocardiography and cardiac catheterisation. The lesions were repaired by open heart surgery under cardiopulmonary bypass. The authors describe the main features of this condition based on their own experience and a review of the literature. PMID- 3090974 TI - [Respiratory insufficiency as a result of paralysis of the diaphragm in acid maltase deficiency]. PMID- 3090975 TI - [Antiaggregatory and anticoagulant actions of oligoamines. 1. 4 Piperidinylmethaneamines]. PMID- 3090976 TI - [The synthesis of potential 5-lipoxygenase inhibitors. 1]. PMID- 3090977 TI - Total cholecystectomy utilization by diagnosis related group. AB - Utilization rates for total cholecystectomy by diagnosis related group in Sacramento, Calif, and Syracuse, NY, between 1981 and 1984 were studied. The two areas had similar hospital discharge rates and bed supplies. The data included 8989 discharges. Discharge rates for the combined cholecystectomy diagnosis related groups differed by only 1% to 3%. Syracuse mean stays for these categories exceeded those of Sacramento by 34% to 38% and were the principal cause of differences in hospital utilization for the procedure. These differences were related to more conservative community-wide physician practice patterns in Syracuse rather than to differences in the composition of the samples by age and payor status, or to the impact of length of stay variability. In the future, shorter stays for cholecystectomy, such as those of Sacramento, may become the norm for the entire nation. PMID- 3090979 TI - Jejunostomy: an indicated procedure? PMID- 3090978 TI - Postoperative enteral vs parenteral nutrition. A randomized controlled trial. AB - Twenty patients undergoing major upper-gastrointestinal-tract or pancreaticobiliary surgery were randomized to receive postoperative nutritional support by total parenteral nutrition (TPN) or elemental diet administered by needle-catheter jejunostomy (NCJ). Both routes of administration provided adequate nutritional support. No unexpected complications were encountered. The NCJ group compared favorably with the TPN group at the end of the seven-day trial. The NCJ group provided significant cost efficiency while maintaining adequate nutritional support. PMID- 3090980 TI - Regulatory mechanism of carbonic acid effect on ammonium nitrogen utilization in animals. PMID- 3090981 TI - Milk urea and protein content to diagnose energy and protein malnutrition of dairy cows. PMID- 3090983 TI - [The most important human aluminoses]. AB - Aluminoses are widespread forms of trace element deficiency of various severity. The organism is protected against a possible pathogenic influence of aluminum by a number of physiological mechanisms the most important among which is a regular urine excretion. A complex of pathological symptoms develops if serious homeostasis disturbances take place e. g. when renal deficiency or direct penetration of the trace element occur. The following forms of aluminosis should be distinguished: 1) simple accumulation in central nervous system which occurs in persons over 65 years; 2) aluminum accumulation in Alzheimer disease, in severe form of presenile and senile dementia; 3) dialysis aluminum encephalopathy; 4) non-dialysis infantile encephalopathy; 5) aluminum encephalopathy in total parenteral nutrition; 6) iatrogenic dialysis aluminum osteodystrophy; 7) jatrogenic peritoneal aluminosis; 8) aluminum pneumoconiosis of an occupational origin; 9) bronchospastic syndrome in aluminum smelter workers. PMID- 3090982 TI - Studies on the genotoxicity of the anabolic drugs trenbolone and zeranol. AB - The androgen trenbolone, and the mycoestrogen zeranol, both anabolic drugs, were tested for their genotoxic potential. Test systems were the SOS-chromotest, the rec-assay and the V79 sister chromatid exchange test without and with metabolic activation using rat liver homogenates and primary rat hepatocytes. It is still a matter of debate if trenbolone has carcinogenic properties, because of its cell transforming activity in vitro. Trenbolone, however, did not demonstrate any genotoxic effect in the assays performed. The results obtained for zeranol were also negative in the SOS-chromotest and V79 sister chromatid exchange test but positive in the rec-assay. PMID- 3090984 TI - [Valproic acid, curly hair and weight gain]. AB - Gain of weight may be observed in up to 20% of patients treated with valproic acid, while changes in hair texture may be found in up to 9%. The author describes the case of a female patient aged 19 years who gained 13 kg and had her hair changed from light, fine blonde to thicker, darker and curly while on valproate acid 1000 mg daily, with a serum level of 138.9 micrograms/ml. After reduction to 500 mg daily, with a serum level of 80.5 micrograms/ml she lost 7 kg but the hair remained unchanged. The patient chose to continue the drug due to complete control of absence, myoclonic and tonic-clonic seizures, which had not been obtained with any other drug before. PMID- 3090985 TI - Endocrine studies in patients with pseudotumor cerebri. Estrogen levels in blood and cerebrospinal fluid. AB - In 15 patients fulfilling conventional diagnostic criteria for pseudotumor cerebri, anterior and posterior pituitary functions were examined. Eight of 12 female patients with pseudotumor were grossly overweight. Except for a subnormal response of growth hormone level to insulin-induced hypoglycemia in four patients, no major disturbances were found in pituitary, gonadal, thyroid, or adrenal functions. Vasopressin concentration in the cerebrospinal fluid was increased in patients with pseudotumor, whereas cerebrospinal fluid concentration of estrogens was below detection limit. PMID- 3090986 TI - A comparison of portal versus systemic venous drainage in murine foetal pancreatic islet transplantation. AB - We have compared the efficiency of foetal islet graft growth and function in renal subcapsular (systemic drainage) and splenic (portal drainage) sites. Age matched female BALB/c streptozotocin (STZ)-diabetic mice were grafted either under the left renal capsule or on to the hilar surface of the spleen with one half of a syngeneic 17-day gestation foetal pancreas which had been in organ culture for 2 weeks. Gain in body weight, return to normoglycaemia and to normal glycosylated haemoglobin levels were not significantly different between the two groups. However, when an intraperitoneal arginine challenge was performed the portally grafted mice showed more normal responses than the systemically grafted mice. Although still not normal after the arginine challenge, mean blood glucose values were lower and serum insulin values higher in the spleen grafted animals than in the renal subcapsular graft group. The total amount of insulin was assayed by extraction of both the graft and the pancreas of each animal. The amount of insulin in the grafts from the spleen was not significantly different from those in the renal subcapsular site. We conclude that the efficiency of a graft draining into the portal circulation is greater than an equivalent sized graft draining systemically when a maximal challenge is applied. PMID- 3090987 TI - Tamoxifen versus chemotherapy as adjuvant treatment in stage III breast cancer. AB - A randomized prospective trial was conducted to compare Tamoxifen and combination chemotherapy (5-fluorouracil, doxorubicin and cyclophosphamide) as adjuvant treatment for patients with locally advanced (Stage III) breast cancer. At the end of 5 years, no significant difference could be found in the disease-free period for both groups. PMID- 3090988 TI - The selection of cases for wedge excision followed by radiotherapy as the treatment of their primary breast cancer. PMID- 3090989 TI - Acquired diverticulosis of the small intestine: case reports and literature review. AB - Eleven cases of small bowel diverticulosis are discussed. Four patients presented with perforation, five with other symptoms attributable to this condition and in two patients diverticulosis was considered an incidental finding. A review of the literature suggests that small bowel diverticulosis may be: present in up to 1.3% of the population; associated with symptoms in approximately 50% of patients, and associated with acute surgical complications in 10% of patients. This may be a disorder of intestinal motility associated with colonic diverticulosis and related to other disorders of smooth muscle and myenteric plexus. Small bowel diverticulosis should not be regarded as a rare, incidental and inconsequential finding. PMID- 3090990 TI - Surgery for pharyngeal pouch. AB - Diverticulectomy for pharyngeal pouch requires several days in hospital and carries a risk of postoperative fistula formation. Small to moderate sized pouches can be inverted easily. Experience with this technique has been encouraging and results are reported here. Large pouches of long standing probably should be excised rather than inverted. PMID- 3090991 TI - Epidemiology and clinical outcomes of neurotrauma in New South Wales. AB - This study of 1161 neurotrauma patients in New South Wales hospitals was designed to examine the role of preventable causes of death and disability in cases of spinal injury, extradural, subdural and multiple intracranial haematomas in order to make recommendations for improvements in accident, emergency, ambulance and hospital services. Methods have been developed for standardizing diagnosis in different classes of hospital for the assessment of severity in terms of the patient's age, sex, physical signs, head and spine injuries and other injuries. Estimates have been made of the number of preventable deaths by a case control study of each category of neurotrauma under study. PMID- 3090992 TI - Diffuse pulmonary ossification and spontaneous pneumothorax in a pilot: a case report. AB - A 51-year-old pilot with spontaneous pneumothorax, emphysema, and multiple horny ossification in the lung is reported. The literature concerning diffuse pulmonary ossification is reviewed and aeromedical implications are discussed. PMID- 3090993 TI - Cases from the aerospace medicine residents' teaching file. Case #13. Pulmonary alveolar proteinosis. PMID- 3090994 TI - The repair of uracil-containing DNA. PMID- 3090995 TI - Application of monoclonal antibodies to monitor human exposure to aflatoxin B1. PMID- 3090996 TI - Immunologic quantification of carcinogen-DNA adducts. AB - Sensitive immunological methods for the detection of carcinogen-DNA adducts have recently been developed. These techniques are particularly useful for screening human populations for exposure to environmental carcinogens. Measurement of the biologically effective dose in humans may be useful in detecting carcinogenic hazards and carrying out risk estimates. We have developed monoclonal antibodies to several carcinogen-DNA adducts. These have included DNA modified by a benzo[a]pyrene diol epoxide (BPDE-I), 1-aminopyrene (1-AP) and 8-methoxypsoralen (8-MOP). BALB/cCr mice were immunized with the modified DNAs complexed electrostatically to methylated bovine serum albumin. Several stable clones have been isolated for each of the modified DNAs and characterized by enzyme-linked immunosorbent assay (ELISA). All antibodies are highly specific for the appropriate modified DNA and do not cross-react with nonmodified DNA. The antibodies to BPDE-I-DNA have significant cross-reactivity with DNAs modified by similar antitrans diol epoxides of benz[a]anthracene and chrysene. These DNAs all contain N-2 of guanine adducts. The antibody probably recognizes a shared determinant encompassing the guanine base and the hydrocarbon ring containing the hydroxide groups. The antibodies cross-react with BPDE-I-dG, the monoadduct isolated from DNA, but with lower sensitivity than for the intact modified DNA. They do not react with acetylaminofluorene (AAF) or 1-AP modified DNA, both of which contain C-8 of guanosine adducts. The antibodies to 1-AP-modified DNA demonstrate cross-reactivity with 8-nitro-1-aminopyrene- and 6-nitro-1 aminopyrene-modified DNA, as well as some slight cross-reactivity with BPDE-I-DNA and AAF-DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3090997 TI - The role of nutritional factors in cellular protection against DNA damage, altered gene expression and malignant transformation. PMID- 3090998 TI - [Schizogony of Sarcocystis ovicanis]. PMID- 3090999 TI - [Modulation of LH and FSH secretion by bovine anterior hypophyseal cell cultures with progesterone]. PMID- 3091000 TI - Purine nucleoside phosphorylase polymorphism in the genus Littorina (Prosobranchia: Mollusca). AB - Examination of eight Atlantic species of the genus Littorina by starch gel electrophoresis of purine nucleoside phosphorylase revealed extensive polymorphism within the L. saxatilis complex. In this group, four alleles have been identified. Heterozygotes are four banded, and thus, as in vertebrates, the enzyme is likely to be a trimer. Breeding experiments confirmed the genetic interpretation of the phenotype patterns. Where species of the saxatilis complex [L. saxatilis (=L. rudis), L. arcana, L. nigrolineata, L. neglecta] are sympatric, there are sometimes significant allele frequency differences between them. A fifth allele was present at a high frequency in L. obtusata and L. mariae, and L. littorea and L. neritoides each possessed unique alleles. A total of eight alleles was identified. Densitometric scanning of heterozygote patterns pointed to activity differences between alleles and also showed that, while the heterotrimeric bands were never less intense than the homotrimeric bands, the heterotrimeric bands were sometimes less intense than expected. It is not clear whether this represents nonrandom association of subunits, decreased stability of heterotrimers, or simply an artifact of the staining and quantifying process. PMID- 3091001 TI - Developmental variation in effects of the second and third chromosomes on the activities of the glucose 6-phosphate and 6-phosphogluconate dehydrogenases in Drosophila melanogaster. AB - Developmental profiles of the second- and third-chromosome modifiers of the activities of glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) in Drosophila melanogaster were investigated. Third chromosome modifiers showed very strong effects on both enzyme activities at larval, pupal, and adult stages, whereas second-chromosome effects were detected mainly at larval and adult stages. For both enzyme activities and both chromosomes, the correlation over line means between larval and pupal stages was significantly positive, but the correlation between larval or pupal stage and adult stage was not significant. This result suggests that the actions of modifiers on G6PD and 6PGD activities are influenced by the change of developmental stages. Correlation between G6PD and 6PGD activities was positive and highly significant throughout the developmental stages for both sets of chromosomes, although third-chromosome correlations were slightly higher than second-chromosome correlations. The magnitude of the correlation between G6PD and 6PGD activities does not seem to be influenced by the change of development. Diallel crosses for both sets of chromosomes indicate that the action of activity modifiers is mainly additive for both sets of chromosomes, but dominance effects were detected in some cases in adult males. Significant maternal effects were detected for the third chromosome for both enzyme activities until the pupal stage. The change of the activity modifier action after emergence of the imago and the significant correlation between G6PD and 6PGD activities were also detected for diallel progeny. PMID- 3091002 TI - GM1 gangliosidosis (type 1) in a cat. AB - A kitten with clinical and morphological symptoms of a neurovisceral lysosomal storage disease has been shown to have a marked deficiency of acidic beta-D galactosidase in the brain, kidney and spleen. Chromatography on concanavalin A Sepharose and inhibition studies with 2,5-dihydroxymethyl-3,4 dihydroxypyrrolidine, a selective inhibitor of the neutral broad-specificity beta D-galactosidase, have shown that the residual beta-D-galactosidase at pH 4.0 in the tissues of the affected cat is due to the neutral beta-D-galactosidase and that there is a complete deficiency of the acidic (lysosomal) beta-D galactosidase. There is marked accumulation in all tissues and excretion in the urine of neutral oligosaccharides. Analysis of these oligosaccharides by fast atom-bombardment mass spectrometry and g.l.c. suggests that they arise from the incomplete catabolism of N-glycans of glycoproteins. The ganglioside content of all the tissues is elevated, and it has been shown by t.l.c. that the concentration of a ganglioside fraction with a mobility similar to that of GM1 ganglioside is particularly increased. There is also some evidence of accumulation of glycosaminoglycans in the brain. The clinical symptoms, the complete deficiency of acidic beta-D-galactosidase and the storage products in visceral organs all suggest that this is a case of feline GM1-type gangliosidosis comparable with the severe infantile (Type 1) form of the disease in humans. PMID- 3091003 TI - Compartmentation and regulation of acetylcholine synthesis at the synapse. AB - Acetylcholine and choline release was measured by using an automated and modified version of the chemiluminescence technique of Israel & Lesbats [(1981) Neurochem. Int. 3, 81-90]. A comparison of acetylcholine and choline release from synaptosomes demonstrated that acetylcholine release was K+-stimulated and inhibited by the Ca2+ ionophore A23187 and cyanide. Choline release, however, did not vary markedly under different conditions, suggesting that it is not associated with acetylcholine release at the nerve ending. Total acetylcholine synthesis in synaptosomal preparations was measured concurrently with the incorporation of [14C]acetyl and [3H]choline moieties by using the chemiluminescence method. Under sub-optimal glucose concentrations or in the absence of treatment of the synaptosomes with the acetylcholinesterase inhibitor phospholine, the incorporation of radioactivity exceeded total synthesis, indicating that cycling between acetylcholine and its precursors may occur. After treatment with phospholine, acetyl-group incorporation from D-[U-14C]glucose occurred without dilution of the precursor at optimal (1.0 mM) and low (0.1 mM) glucose concentrations; however, at very low (0.01 mM) glucose concentrations, dilution by a small endogenous pool occurred. [14C]Acetyl incorporation into acetylcholine was compared with various metabolic parameters. A closer correlation was observed between [14C]acetyl-group incorporation into acetylcholine and the calculated acetyl-carrier efflux from the mitochondria than with the calculated pyruvate-dehydrogenase-complex flux. The results are discussed with respect to the regulation of acetylcholine concentrations at the synapse and the mechanism whereby turnover occurs. PMID- 3091004 TI - Studies of the influence of chloro-substituent sites and conformational energy in polychlorinated biphenyls on uroporphyrin formation in chick-embryo liver cell cultures. AB - Treatment of cultured chick-embryo liver cells with polychlorinated biphenyls (PCB) results in decreased uroporphyrinogen decarboxylase activity and increased uroporphyrin accumulation. In the present study we examined the effect of the chloro- or bromo-substituent sites in biphenyls (BP) on uroporphyrin accumulation in cultured hepatocytes and the three-dimensional structure of these congeners determined by molecular orbital calculations using a MNDO ('modified neglect of diatomic overlap') method. Among 20 congeners examined, those which were effective in stimulating porphyrin accumulation contained at least two Cl or Br atoms at the lateral adjacent positions in each phenyl ring, e.g. 3,4,3',4' tetrachloro-, 2,4,3',4'-tetrachloro-, 3,4,5,3',4',5'-hexachloro- and 3,4,5,3',4',5'-hexabromobiphenyl, whereas those which contained less than two halogen atoms or more than three halogen atoms in each phenyl ring or those which contained halogen atoms at 2,2'-positions were not effective. On the basis of the conformational energy (delta E, difference from the most stable conformational energy), which is calculated as a function of the dihedral angle (theta) between the two phenyl rings, biphenyl congeners can be classified into four groups with different conformations. The conformation of active PCB was relatively flexible, whereas inactive species had a rigidly angulated conformation. Furthermore, the calculated probability of the conformation distribution for each congener indicated that the probability of co-planarity was higher for active biphenyls than for inactive congeners. These structural characteristics suggest the significance of both the chloro-substituent sites and the conformational energy reflecting the phenyl-ring twist angles in determining the inhibitory effect of PCB on uroporphyrinogen decarboxylase activity. PMID- 3091005 TI - Effect of methimazole on the activity of mushroom tyrosinase. AB - Methimazole (1-methyl-2-mercaptoimidazole) inhibits both the mono- and the o dihydroxyphenolase activities of mushroom tyrosinase when assayed spectrophotometrically. With DL-3,4-dihydroxyphenylalanine as substrate, the inhibition was found to be a mixed-type one with Ki 4.6 X 10(-6) M. We found that methimazole can interact with the oxidation products of o-dihydroxyphenols, probably with o-quinones, to form a conjugate. The conjugate formed between methimazole and o-benzoquinone was separated by chromatography on Sephadex G-10 and was characterized by an absorption maximum at 248-260 nm. Our data suggest that methimazole inhibits mushroom tyrosinase activity in two ways: by conjugating with o-quinones, thereby causing an apparent inhibition in pigmented product formation as judged by the spectrophotometric assay; and by chelating copper at the active site of the enzyme, as judged by assaying the release of 3HHO from L-[3,5-3H]tyrosine. PMID- 3091006 TI - Purification and characterization of the NADPH-cytochrome P-450 (cytochrome c) reductase from higher-plant microsomal fraction. AB - NADPH-cytochrome P-450 (cytochrome c) reductase (EC 1.6.2.4) was solubilized by detergent from microsomal fraction of wounded Jerusalem-artichoke (Helianthus tuberosus L.) tubers and purified to electrophoretic homogeneity. The purification was achieved by two anion-exchange columns and by affinity chromatography on 2',5'-bisphosphoadenosine-Sepharose 4B. An Mr value of 82,000 was obtained by SDS/polyacrylamide-gel electrophoresis. The purified enzyme exhibited typical flavoprotein redox spectra and contained equimolar quantities of FAD and FMN. The purified enzyme followed Michaelis-Menten kinetics with Km values of 20 microM for NADPH and 6.3 microM for cytochrome c. In contrast, with NADH as substrate this enzyme exhibited biphasic kinetics with Km values ranging from 46 microM to 54 mM. Substrate saturation curves as a function of NADPH at fixed concentration of cytochrome c are compatible with a sequential type of substrate-addition mechanism. The enzyme was able to reconstitute cinnamate 4 hydroxylase activity when associated with partially purified tuber cytochrome P 450 and dilauroyl phosphatidylcholine in the presence of NADPH. Rabbit antibodies directed against plant NADPH-cytochrome c reductase affected only weakly NADH sustained reduction of cytochrome c, but inhibited strongly NADPH-cytochrome c reductase and NADPH- or NADH-dependent cinnamate hydroxylase activities from Jerusalem-artichoke microsomal fraction. PMID- 3091007 TI - Quantification of tissue-type plasminogen activator (t-PA) mRNA in human endothelial-cell cultures by hybridization with a t-PA cDNA probe. AB - We describe the construction of a recombinant DNA plasmid, consisting of the vector pBR322 and full-length tissue-type plasminogen-activator (t-PA) cDNA, by using polyadenylated RNA from cultured Bowes melanoma cells as substrate. A 1280 base-pair PstI restriction fragment, covering the 3' untranslated region and part of the coding region for the t-PA L-chain, was used as a radiolabelled probe to determine the size and the number of t-PA mRNA molecules in cultured endothelial cells of different origin from the same individual. Northern blotting showed that in all these cells a t-PA mRNA is synthesized of about 2500 nucleotides, indicating that transcriptional initiation, splicing and polyadenylation is similar. The number of t-PA mRNA molecules per cell measured, by using a dot blotting technique and t-PA mRNA made in vitro, with a plasmid DNA preparation harbouring a specific promotor of the Salmonella typhimurium bacteriophage SP6, t PA cDNA and SP6 RNA polymerase as standard, is approx. 10,000 in all cultured endothelial cells from adult vessels. However, the amount of t-PA antigen synthesized and/or secreted differs by a factor of 6-20. Relatively large amounts of t-PA antigen secreted were detected in conditioned medium from vena-cava derived cells, whereas low amounts were found in conditioned medium from arteria iliaca-derived cells. PMID- 3091008 TI - The role of tetrahydromethanopterin and cytoplasmic cofactor in methane synthesis. AB - A fraction previously isolated from acid-treated supernatant fraction of Methanobacterium thermoautotrophicum by DEAE-Sephadex chromatography [Sauer, Mahadevan & Erfle (1984) Biochem. J. 221, 61-97] which was absolutely required for methane synthesis, has been separated into two compounds, tetrahydromethanopterin (H4MPT) and an as-yet-unidentified cofactor we call 'cytoplasmic cofactor'. H4MPT was identified by its u.v. spectrum and by 13C- and 1H-n.m.r. spectroscopy. The reduction of 2-(methylthio)ethanesulphonic acid (CH3 S-CoM) to methane by the membrane fraction from M. thermoautotrophicum was completely dependent on the addition of cytoplasmic cofactor. Methane synthesis from CO2, however, was only partially dependent on cofactor addition, and 57% of the original activity was retained in its absence. The kinetics of 14C labelling were consistent with the scheme methyl-H4MPT----CH3-S-CoM----methane, as has been proposed. This is the first time that direct experimental evidence has been presented to show that the proposed methyl transfer from H4MPT to coenzyme M (HS CoM) actually occurs. PMID- 3091010 TI - Biochemical studies on proacrosin and acrosin from epididymal boar spermatozoa: in vitro translation of boar testicular proacrosin mRNA. AB - An inactive form of acrosin was extracted from epididymal boar spermatozoa utilizing acid pH conditions. When subjected to activation in alkaline environment, this form turns into an enzymatically active species, which exhibits close-related electrophoretic characteristics. Both the precursor and the activated species, when incubated in the presence of thermolysin, give rise to two fastly moving acrosin molecular forms. In order to establish the nature of the true acrosin zymogen, we isolated poly(A+)-RNA from boar testicles, performed its translation in vitro in the presence of [35S]-methionine and reticulocyte lysate, immunoprecipitated the translation products with anti-boar acrosin antibody, and analyzed them by SDS-polyacrylamide gel electrophoresis and autoradiography. A single translation product of molecular weight 55,000 was detected. It is concluded that the polypeptide chain of the boar zymogen is of 55,000; increases in molecular weight are due to post-translational modifications, like glycosylation. PMID- 3091011 TI - Involvement of sulfatide in activation of protein kinase C by tumor promoters. AB - Sulfatide (cerebroside sulfate) activated protein kinase C to the same extent as phosphatidylserine did with the tumor promoters, 12-O-tetradecanoylphorbol-13 acetate (TPA), teleocidin and debromoaplysiatoxin. Sulfatide and phosphatidylserine both induced specific binding of [3H]TPA to protein kinase C, although the ratios of specific to non-specific [3H]TPA binding to protein kinase C with the two were not the same. It is concluded that sulfatide is involved in activation of protein kinase C by tumor promoters in a slightly different way from phosphatidylserine. PMID- 3091009 TI - Studies on lipid peroxidation in normal and tumour tissues. The Novikoff rat liver tumour. AB - A study has been made of the factors that contribute to the decreased rates of lipid peroxidation under different pro-oxidant conditions in intact Novikoff tumour cells, and in microsomal suspensions prepared from Novikoff tumour cells, compared with isolated normal rat hepatocytes and microsomal suspensions prepared from normal rat liver. The pro-oxidant conditions were the addition of either NADPH, NADPH + ADP + iron, NADPH + CCl4 or ascorbate+iron to the experimental systems used, or exposure to gamma-radiation. Contributory factors to the lower rates of lipid peroxidation observed include: a significant decrease in the polyunsaturated fatty acid content of Novikoff cells or Novikoff microsomes; the decreases are especially marked for the C20:4 and C22:6 fatty acids; a very marked reduction in NADPH-cytochrome c reductase; and no detectable content of cytochrome P-450. Another, and in our opinion critical, contribution to the diminished rate of lipid peroxidation in the tumour material is the substantial increase in alpha-tocopherol relative both to total lipid and to methylene interrupted double bonds in fatty acids. Moreover, the alpha-tocopherol is the major contributor to lipid-soluble chain-breaking antioxidant in lipid extracts of normal liver and of Novikoff tumour material. PMID- 3091012 TI - Evidence for high peptide alpha-amidation activity in the neonatal rat pancreas. AB - A high peptide alpha-amidating activity is present in a mitochondrial/secretory granules preparation from 3-day old rat pancreas. It is dependent on copper, ascorbate and molecular oxygen. This preparation is able to generate TRH when incubated with Pyroglu-His-Pro-Gly, a sequence present in the TRH precursor molecular. The peptide alpha-amidating activity may be involved in the high rate of TRH biosynthesis in the pancreas during the neonatal period. In the pancreas of adult rats which contain low levels of TRH, the peptide alpha-amidating activity is barely detectable. PMID- 3091013 TI - Isolation of galactosyltransferase from human milk and the determination of its N terminal amino acid sequence. AB - Galactosyltransferase (EC 2.4.1.22), purified to homogeneity from human milk by affinity chromatography, had an apparent molecular weight of 53,000 as determined by denaturing polyacrylamide gel electrophoresis. Subtraction of the estimated contribution of the oligosaccharide portion of the molecule leaves a Mr of 47,000. An N-terminal amino acid sequence analysis of the isolated protein revealed a sequence similar to that found near the 5' end of a cDNA clone isolated by Shaper et al, which encodes a 35,000 molecular weight protein. Either the molecular weight of galactosyltransferase, has been overestimated, or a discrepancy exists between the actual molecular weight of galactosyltransferase and that predicted by the bovine cDNA clone isolated by Shaper et al. PMID- 3091014 TI - Enzymatic deglycosylation of thyroid-stimulating hormone with peptide N glycosidase F and endo-beta-N-acetylglucosaminidase F. AB - We investigated the ability of two enzymes, peptide N-glycosidase F (PNGase F) and endo-beta-N-acetylglucosaminidase F (Endo F), to deglycosylate microgram quantities of bovine TSH and its subunits under nondenaturing conditions. One oligosaccharide chain could be selectively removed from the alpha subunit by PNGase F, and all the oligosaccharide chains from both subunits could be removed by Endo F. These methods of enzymatic deglycosylation should permit study of the functional role of each N-linked carbohydrate chain of various glycoprotein hormones. PMID- 3091015 TI - Carcinogen metabolism in human skin grafted onto athymic nude mice: a model system for the study of human skin carcinogenesis. AB - Human skin grafted onto athymic nude mice maintains its major histological features and may provide a useful system with which to assess the carcinogen interaction with human skin. Significant differences were observed in basal levels of cytochrome P-450 and cytochrome P-448-dependent monooxygenase activities between human grafted and nude mouse epidermis. Topical application of crude coal tar (CCT) to human skin transplanted onto nude mice resulted in 3.9 & 3.5; 3.2 & 2.9 and 1.1 & 1.2 fold increases in mouse and human epidermal aryl hydrocarbon hydroxylase (AHH), ethoxyresorufin deethylase (ERD) and ethoxycoumarin deethylase (ECD) activities, respectively. CCT applied topically to mouse skin resulted in 27.8 & 6.4; 12.8 & 3.3 and 1.7 & 2.6 fold increases in mouse and human epidermal AHH, ERD and ECD activities, respectively. Topical application of coal tar either onto human transplanted skin or to mouse skin also resulted in substantial induction of hepatic and pulmonary AHH and ERD activities. These studies indicate that human skin grafted onto nude mice preserves its metabolic capacity and offers a useful model system with which to assess the effects of polycyclic aromatic hydrocarbons and CCT on cutaneous xenobiotic metabolism in the human population. PMID- 3091016 TI - Comparison of in vitro and in vivo effects of different species specific GnRH and their analogs. AB - Mammalian, salmon and chicken gonadotropin-releasing hormones (mGnRH, sGnRH, cGnRH) and their analogs were synthesized and tested for their ability to stimulate in vitro LH and FSH release from cultured and superfused rat pituitary cells and also their in vivo effect were investigated on the artificial propagation of fishes. The LH and FSH releasing activity of sGnRH, cGnRH and their analogs were lower than the appropriate mammalian ones from cultured rat pituitary cells, but two of the cGnRH analogs showed increased LH and FSH secretory activity from superfused rat pituitary cells compared to the mGnRH. At the same time these two analogs are very potent to stimulate reproductive function of fishes and using these peptides we were able to fulfill the artificial propagation of fishes which could not be artificially propagated before. PMID- 3091018 TI - Calcium ionophore A23187 primes human B-cells for activation by phorbol dibutyrate by converting receptors for phorbol dibutyrate from a low to high affinity state. AB - The calcium ionophore A23187 synergised with phorbol dibutyrate-induced activation of human chronic lymphatic leukaemia B-cells, as assessed by modulation of the membrane receptor for mouse erythrocytes. Thus A23187 (1 microM), which alone had no effect on expression of the receptor for mouse erythrocytes, reduced the EC50 and shortened the lag period for modulation of this receptor by phorbol dibutyrate. This action of A23187 was shown to be due to enhanced binding of [3H]phorbol dibutyrate to its receptor (phospholipid/Ca++ dependent protein kinase C) whose affinity was altered from a predominantly low affinity state (Kd 83 nM) to high affinity (Kd 9 nM). A23187 had no effect on the total number of phorbol dibutyrate receptors. EDTA abolished these actions of A23187. PMID- 3091019 TI - L-aspartate ammonia-lyase and fumarate hydratase share extensive sequence homology. AB - Based on our recent determinations of the nucleotide sequences of the L-aspartate ammonia-lyase genes from Escherichia coli and Pseudomonas fluorescens, primary structures of the two L-aspartate ammonia-lyases and fumarate hydratases from Bacillus subtilis and E. coli (N-terminal partial sequence) were compared by computer analysis. These four enzymes exhibited a significant homology of at least 37%, implying that L-aspartate ammonia-lyase and fumarate hydratase share a common evolutionary origin. To authors' knowledge, this feature appears to be the first example showing that two kinds of enzymes catalyzing different types of reactions, albeit similar, share such a high degree of sequence homology. PMID- 3091017 TI - A rapid apolipoprotein E radioimmunoassay using solid-phase staphylococcus protein. Use of pooled plasma as a secondary standard. AB - A rapid apolipoprotein E (apo E) radioimmunoassay, which requires a total of 24 hour incubation as compared to the usual 3-5 days, has been developed in our laboratory. Solid phase staphylococcus protein A was used to separate bound and unbound labeled antigen. Use of a pooled plasma (quality control sample) as a secondary standard to reduce interassay variation was also described. PMID- 3091020 TI - D-ribose inhibits DNA repair synthesis in human lymphocytes. AB - D-ribose is cytotoxic for quiescent human lymphocytes and severely inhibits their PHA-induced proliferation at concentrations (25-50 mM) at which other simple sugars are ineffective. In order to explain these effects, DNA repair synthesis was evaluated in PHA-stimulated human lymphocytes treated with hydroxyurea and irradiated. D-ribose, in contrast to other reducing sugars, did not induce repair synthesis and therefore did not apparently damage DNA in a direct way, although it markedly inhibited gamma ray-induced repair. Taking into account that lymphocytes must rejoin physiologically-formed DNA strand breaks in order to enter the cell cycle, we suggest that D-ribose exerts its cytotoxic activity by interfering with metabolic pathways critical for the repair of DNA breaks. PMID- 3091021 TI - Spermatozoa contain a guanine nucleotide-binding protein ADP-ribosylated by pertussis toxin. AB - Spermatozoa from invertebrates (sea urchin, starfish) and vertebrates (trout, guinea pig, bull, pig, human) contain a membrane-bound protein that is ADP ribosylated by pertussis toxin but not by cholera toxin. The Mr of this protein is 39,000 in invertebrate sperm and 41,000 in mammalian sperm, but 40,000 in trout spermatozoa. The pertussis toxin substrate from sea urchin sperm copurified with [gamma-35S]GTP binding activity. Chymotryptic maps of this ADP-ribosylated protein from sea urchin sperm were the same as those of alpha-subunit of Go from rat brain. Antiserum to the beta-subunit of bovine retinal transducin bound to a sperm protein with Mr approximately 35,000. These studies are the first describing a guanine nucleotide-binding coupling protein in sperm. PMID- 3091022 TI - Induction of L-alanine:4,5-dioxovalerate transaminase by phenylhydrazine is associated with depletion of heme level. AB - The hemin regulation of L-alanine:4,5-dioxovalerate transaminase, the enzyme proposed for an alternate route of delta-aminolevulinic acid (ALA) biosynthesis in mammalian system was studied in different conditions: phenylhydrazine induced anemia, polycythemia by erythropoietin to anemic rats, treatment with cobalt chloride, a porphyrogenic drug. The activity of L- alanine:4,5-dioxovalerate transaminase in liver and kidney is stimulated in phenylhydrazine, whereas, erythropoietin injection to anemic rats prevents such stimulation. Further treatment with cobalt chloride to erythropoietin treated anemic rats stimulates the enzyme activity. Actinomycin D, however, inhibits the stimulation of L alanine:4,5-dioxovalerate transaminase by phenylhydrazine suggesting that induction is at the level of transcription. Induced level of this enzyme in anemic condition was estimated quantitatively by radial immunodiffusion using antibody raised against L-alanine:4,5-dioxovalerate transaminase. Moreover, our studies reveal that stimulation of L-alanine:4,5-dioxovalerate transaminase in anemic condition is dependent on depletion of heme level. The regulatory role of intracellular heme pool on the induction of this enzyme suggests its physiological importance in heme biosynthesis. PMID- 3091023 TI - Putrescine does not mediate the androgen-response in mouse kidney. AB - We have tested the notion that polyamines, particularly putrescine, mediate the response of mouse kidney to androgens. Hormonal effects were measured in female mice maintained on the ornithine decarboxylase (ODC) inhibitor alpha difluoromethylornithine (DFMO), which results in a 85-90% reduction of ODC enzyme levels and a depletion of putrescine concentrations in kidney. These animals exhibited normal kidney cell hypertrophy in response to testosterone. In addition, androgen-inducibility of the RP2 gene was indistinguishable from that in normal mice. These results indicate that an increase in putrescine levels is not a prerequisite for androgen effects in mouse kidney and that putrescine does not mediate the hormonal response. PMID- 3091024 TI - Involvement of lipoxygenases in the activation of mouse macrophages by endotoxin. AB - Preincubation with lipopolysaccharides stimulated the phagocytic capacity of mouse peritoneal macrophages. Treatment of cell cultures with inhibitors of lipoxygenases which affect this pathway specifically (diethylcarbamazine) or compounds which block lipoxygenases and cyclooxygenase (BW 755 C, eicosatetraynoic acid) inhibited the increase, while inhibitors of cyclooxygenase (indomethacin, aspirin) did not affect the LPS induced enhancement of the phagocytic capacity. It is, therefore, concluded that lipoxygenase products are required for the activation of macrophages by endotoxins. PMID- 3091025 TI - Control of rRNA transcription in liver of mice exposed to nutritional changes: initiation frequency may be a regulatory mechanism. AB - Shortly after feeding protein-depleted mice on a meal containing proteins, the RNA polymerase I activity in isolated liver nuclei shows a two fold to threefold activation over the basal value in nuclei of either normal or protein-depleted mice. This activation can be accounted for by the increase in the number of growing rRNA chains. Moreover, the template-bound RNA polymerase I fraction in nuclei from re-fed mice is about three times that from protein-depleted animals. An excess of template- unbound enzyme was found in liver nuclei from animals under either nutritional condition. Shortly after inhibition of protein synthesis by pactamycin administration to re-fed mice, the number of transcribing RNA polymerase I molecules in liver nuclei decreases to the basal level found in nuclei from protein-depleted mice, while in the latter, protein synthesis inhibition has no effect. These results support the suggestion that short-lived proteins may enhance the initiation frequency by RNA polymerase I after re feeding. PMID- 3091026 TI - Significance of transported glycine in the conjugation of sodium benzoate in spf mutant mice with ornithine transcarbamylase deficiency. AB - 3H-glycine and 14C-serine were injected intraperitoneally, during treatment of spf mutant mice with 2% sodium benzoate in drinking water. Urinary hippurate was separated by thin layer chromatography and counted for 3H and 14C labels representing transported and newly synthesized glycine, respectively. The specific activity of 3H-hippurate increased significantly in mutant and normal groups, while the increase of 14C was seen only in mutants. The ratio of specific activity 3H:14C showed significant increases in normal (0.99 to 1.93; p less than 0.01) and mutant (1.53 to 3.05; p less than 0.05) groups, which shows that glycine transported from body pools played a significantly greater role in the conjugation of benzoate, compared to glycine synthesized de novo from serine. In spf mice, benzoate treatment also resulted in a decrease in orotate excretion, indicating amelioration of the hyperammonemic state. It is postulated that the elimination of glycine transported from body pools may be the primary mechanism for the reduction of ammoniagenicity in benzoate therapy, and that the de novo synthesis of glycine may have a secondary effect. PMID- 3091027 TI - Lipoic acid provokes inhibition and aggregation of the maltose binding protein of Escherichia coli. AB - Lipoic acid provokes aggregation of the monomeric maltose binding protein of Escherichia Coli into dimers and tetramers, and inhibits maltose binding. The sigmoidal shape of the curves showing the dependence of maltose binding versus lipoic acid concentration, and versus maltose concentration (in the presence of lipoic acid) suggests that the inhibition of the maltose binding protein by lipoic acid is a consequence of its aggregation. These results are discussed in relation to recent studies describing dimers of the maltose binding protein purified under certain conditions, and in relation to results suggesting an implication of lipoic acid in the binding protein-dependent transports. PMID- 3091028 TI - A clone coding for Schizophyllum commune beta-glucosidase: homology with a yeast beta-glucosidase. AB - Three identical clones coding for a partial sequence of the Schizophyllum commune beta-glucosidase were isolated from a cDNA library in lambda gt11, using polyclonal antibody to the enzyme. The identity was confirmed by comparison of the amino-terminus of a peptide from a protease lys-C digest with the sequence inferred from the cDNA sequence. A comparison of the sequence with that reported for a beta-glucosidase from Candida pelliculosa revealed a region in the latter with 43% identity in amino acid sequence. There was also a similarity in the S. commune beta-glucosidase to an active site sequence proposed for a S. commune endoglucanase, suggesting the possibility of a common catalytic mechanism for these two glucolytic enzymes. PMID- 3091029 TI - Effects of griseofulvin on enzymes associated with phase I and II of drug metabolism. PMID- 3091030 TI - Decarboxylation of 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acids in brain homogenate and catalysis by pyridoxal-5'-phosphate. AB - [Carboxyl-14C] labelled 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (I) and 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (II) were synthesized and their decarboxylation was studied in mouse brain homogenate and buffer. The decarboxylation rates of (I) and (II) in the homogenate were about 6 fold and 4-fold, respectively, as compared with the rates in phosphate buffer. The increase could not be prevented by preheating the homogenate, but was partially abolished by addition of 1 mM EDTA. The decarboxylation was increased dose-dependently when pyridoxal-5'-phosphate was included in the buffer, 400 microM being sufficient to exceed the rate in homogenate for both (I) and (II). Mass spectrometric examination of the decarboxylation products indicated that both (I) and (II) were degraded mainly to corresponding 1,2,3,4-tetrahydro-beta carbolines, but some 3,4-dihydro analogues also were detectable. In conclusion, the results outline a way through which these pharmacologically active beta carbolines are readily formed under conditions that may be regarded as physiological. PMID- 3091031 TI - Changes in hamster hepatic cytochrome P-450, ethoxycoumarin O-deethylase, and reduced NAD(P): menadione oxidoreductase following treatment with 2,3,7,8 tetrachlorodibenzo-p-dioxin. Partial dissociation of temporal and dose-response relationships from elicited toxicity. AB - The temporal and dose-related characteristics of hepatic enzymes induced in the hamster by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were examined. Male Syrian golden hamsters received a single intraperitoneal injection of TCDD at a dose of 0-500 micrograms/kg. At various times up to 35 days, a number of variables were determined and compared: whole body, liver, and thymus weights; hepatic concentrations of cytochrome P-450 (P-450); and activities of 7-ethoxycoumarin O deethylase (ECOD) and reduced NAD(P): menadione oxidoreductase (NMOR). Increased liver weights and decreased thymus weights were observed to be dose related. At day 7 following treatment, the approximate ED50 values for these responses were 15 and 100 micrograms/kg respectively. The ED50 values for the increase in hepatic P-450 concentrations and activities of ECOD and NMOR ranged from 0.5 to 2.0 micrograms/kg. At 10 and 500 micrograms/kg, NMOR activity remained maximally induced for up to 35 days. This was also the case for P-450 and ECOD activity at a dose of 10 micrograms/kg. At 500 micrograms/kg, both P-450 and ECOD demonstrated an induction up to day 4 followed by a decrease to near control levels by day 14. This decrease appeared to correlate with changes in hepatic morphology. These results demonstrate a dissociation of the induction of these hepatic enzymes from TCDD-induced lethality, in this species. PMID- 3091033 TI - Glibenclamide induces glucokinase in rat pancreatic islets and liver. PMID- 3091032 TI - Kinin and enkephalin conversion by an endothelial, plasma membrane carboxypeptidase. AB - Utilizing both thin-layer chromatography and high pressure liquid chromatography, it was determined that a vascular plasma membrane preparation contains a carboxypeptidase capable of converting kinins (B2 agonists) to des(Arg)kinins (B1 agonists) by hydrolysis of C-terminal Arg. The plasma membrane carboxypeptidase also converted Leu5-enkephalin-Arg6 to Leu5-enkephalin. Carboxypeptidase activity was significantly higher in cultured endothelial (1.47 +/- 0.4 units/mg) than in cultured smooth muscle cells (0.16 +/- 0.4 units/mg). Both the vascular and endothelial activities had neutral pH optima and were activated 4- to 5-fold by 0.1 mM CoCl2. The carboxypeptidase N inhibitor MERGETPA (D-L-mercaptoethanol-3 guanidino-ethylthiopropanoic acid) inhibited the plasma membrane bound carboxypeptidase with an I50 of 0.3 microM. Conversion was also inhibited by o phenanthroline and EDTA, whereas inhibitors of aminopeptidases (bestatin, puromycin), endopeptidases (phosphoramidon), "enkephalinase" (ZINCOV) or enkephalin convertase (PCMS) were without effect. The affinity of the endothelial plasma membrane carboxypeptidase for bradykinin (Km = 56.8 +/- 4.7 microM) was higher than that for Leu5-enkephalin-Arg6 (Km = 92.7 +/- 10.1 microM), whereas the maximal rates of conversion (calculated per mg of endothelial plasma membrane protein) were similar (17.1 and 21.3 nmoles/min/mg respectively). These results demonstrate that a carboxypeptidase is present on the cell surface of vascular endothelium which can convert kinins and enkephalins in the micro-environments of vascular cell surface receptors. PMID- 3091034 TI - Substrate-selective induction of rabbit hepatic UDP-glucuronyltransferases by ethanol and other xenobiotics. AB - Male New Zealand white rabbits were treated with various inducers of hepatic metabolism enzymes to characterize the induction of UDP-glucuronyltransferase (UDP-GT) enzymes. Rabbits were pretreated with phenobarbital, 1,1,1-trichloro-2,2 bis(p-chlorophenyl)ethane (DDT), 3-methylcholanthrene, beta-naphthoflavone, Aroclor 1254, ethanol, trans-stilbene oxide, pregnenolone-16 alpha-carbonitrile, or clofibric acid. Hepatic microsomes from treated and control animals were incubated with the GT1-type substrates, p-nitrophenol and 1-naphthol; the GT2 type substrate, morphine; and the steroid substrate, estrone. Compared to the rat, the rabbit was particularly resistant to UDP-GT induction. Ethanol was the most potent inducer for both GT1 and GT2 activities, but it failed to induce steroid (estrone, estradiol, and testosterone) UDP-GT activities. Ethanol pretreatment increased oxazepam-GT but it decreased bilirubin-GT activity. 3 Methylcholanthrene (3MC) and beta-naphthoflavone (BNF) are the prototypic GT1 inducers in the rat, but 3MC caused no induction of GT1 activity and BNF caused induction of both GT1 and GT2 activities in the rabbit. None of the xenobiotic pretreatments increased the hepatic microsomal glucuronidation of estrone. These results demonstrate that the induction of UDP-GT activities, and the use of this phenomenon to classify UDP-GT forms, is somewhat species-specific and cannot necessarily be extrapolated from rats to other species. In addition, the substrate selectivity of ethanol-induced microsomal UDP-GT was established. PMID- 3091035 TI - Comparison of the effect of two different hypoglycemic agents, glibenclamide and HB 699, on the rat small intestinal absorption of sugars and amino acids. AB - 4-(2-[5-Chloro-2-methoxy-benzamido]-ethyl)-benzoic acid (HB 699) belongs to the group of hypoglycemic benzoic acid derivatives. Although lacking the sulfonylurea group, the structure of HB 699 partly resembles that of glibenclamide which is known to impair small-intestinal glucose absorption in vitro at high concentrations. Whereas this intestinal effect of glibenclamide is unlikely to contribute to its blood-glucose lowering properties, extrapancreatic and particularly intestinal effects may be important for the antidiabetic action of HB 699. Thus, HB 699 was compared with glibenclamide for the effect on the small intestinal absorption of sugars and amino acids in vitro (everted-sac and tissue accumulation technique) and in vivo (single-pass perfusion of the jejunum). In vitro both drugs inhibited the active transport of sugars and amino acids in a dose dependent manner. At equieffective doses (HB 699, 4.5 mmol/l and glibenclamide, 1 mmol/l) the mode of inhibition by the two drugs was similar. A 30-min incubation period reduced the uptake of methyl alpha-D-glucoside by about 75%. The degree of inhibition depended on the time of exposure of the tissue to the drugs. In vitro kinetic studies revealed a mixed type of inhibition. The in vivo effect of the drugs was in accordance with the in vitro findings. Inhibition, as in vitro, was not reversible and even increased further after reinfusion of a drug-free perfusate. In vivo, the drugs inhibited the absorption of methyl alpha-D-glucoside and leucine only at low (less than 20 mmol/l) but not at high (greater than 30 mmol/l) solute concentrations. These results indicate that hypoglycemic benzoic acid derivatives may exert their blood-glucose lowering properties in part by impairing the small-intestinal active transport of glucose. PMID- 3091036 TI - Inhibition of hexonate dehydrogenase and aldose reductase from bovine retina by sorbinil, statil, M79175 and valproate. AB - Aldose reductase inhibitors (A.R.I.s), developed as potentially therapeutic agents for the treatment of complications of long-term diabetes, were found to be potent inhibitors of aldose reductase (ALR2) partially purified from bovine retina (IC50 values: Statil 0.89 microM, Sorbinil 2 microM, M79175 greater than 1 microM). These compounds varied, however, in their ability to inhibit hexonate dehydrogenase (ALR1), a closely related enzyme isolated from the same source (IC50 values: Statil greater than 1 microM, Sorbinil 3.9 microM, M79175 0.18 microM). Statil and Sorbinil were active against ALR2 at very low concentrations (approx. 5% inhibition at 100 pM), but did not inhibit ALR1 at less than or equal to 10 nM. In contrast, M79175 (structurally very similar to Sorbinil) and M7HEQ (a flavonoid) were preferential inhibitors of ALR1. Valproate, a compound of value in the treatment of epilepsies, was a poor inhibitor of ALR2 (18% at 1 mM). Furthermore, valproate was found to be a relatively poor inhibitor of ALR1, particularly in comparison with M79175. PMID- 3091037 TI - The activity of UDP-glucuronyltransferase, sulphotransferase and glutathione-S transferase in primary cultures of rat hepatocytes. PMID- 3091038 TI - Formation of a synovial-like membrane at the bone-cement interface. Its role in bone resorption and implant loosening after total hip replacement. AB - Histologic evaluation of tissue surrounding the loosened components after joint replacement reveals the presence of a synovial-like lining adjacent to the polymethyl methacrylate cement. The tissue is heavily infiltrated with particulate cement as well as polyethylene associated with a foreign body-type giant cell reaction. That this tissue response may be responsible for the bone lysis associated with loosening is suggested by the demonstration of high prostaglandin E2 levels and enhanced bone resorbing activity in the tissue culture medium of fragments from this membrane. PMID- 3091039 TI - Inhibition of excessive scleroderma fibroblast collagen production by recombinant gamma-interferon. Association with a coordinate decrease in types I and III procollagen messenger RNA levels. AB - The effects of recombinant gamma-interferon (rec gamma-IFN) on collagen production by confluent monolayer cultures of progressive systemic sclerosis (PSS) dermal fibroblasts were studied. Five cell lines obtained from patients with rapidly progressive disease of recent onset were examined. All PSS fibroblast cell lines exhibited increased collagen production when compared with normal skin cell lines. It was found that rec gamma-IFN caused potent inhibition of PSS fibroblast collagen production in a concentration-dependent manner. Greater than 50% inhibition was observed with as little as 50 antiviral units/ml, and maximal effects were attained at a concentration of 500 units/ml. The rec gamma-IFN caused reproducible inhibition of collagen production by the 5 PSS fibroblast cell lines, ranging from 58.9% to 85.6% of control values. Measurement of type I and type III procollagen messenger RNA (mRNA) levels with specific complementary DNA probes demonstrated a coordinate reduction of greater than 60% in mRNA for both transcripts in rec gamma-IFN-treated cells, compared with control cells. These findings indicate that rec gamma-IFN can modulate the excessive collagen biosynthesis characteristic of PSS fibroblasts and that this effect can be explained largely by the gamma-IFN-mediated decrease in specific collagen mRNAs. PMID- 3091040 TI - The neurotoxic effect of gold sodium thiomalate on the peripheral nerves of the rat. Insights into the antiinflammatory actions of gold therapy. AB - Although gold is one of the few therapeutic agents that has been proven effective in producing remission in patients with rheumatoid arthritis, its mechanism of action is unknown. Since nociceptive afferent and sympathetic efferent fibers of the peripheral nervous system contribute to the pathophysiology of inflammation, and since a known side effect of gold therapy is a polyneuropathy, we tested the hypothesis that gold is toxic to small-diameter peripheral nerve fibers in the rat. We found that prolonged treatment with gold, at the same dosage reported to be effective against adjuvant-induced arthritis in the rat, produced a significant decrease in the numbers of unmyelinated, but not of myelinated, axons. Gold treatment also elevated nociceptive thresholds in both articular and nonarticular structures. These results suggest that gold produces an antiinflammatory effect on arthritis by a neurotoxic effect on the peripheral nerves involved in neurogenic inflammation. PMID- 3091041 TI - Cost-effectiveness of total joint arthroplasty in osteoarthritis. AB - Although total joint replacement (TJR) is a major advance in the treatment of patients with osteoarthritis, its cost-effectiveness has been questioned. We report the results of a study of the costs and benefits of TJR in consecutive osteoarthritis patients, 6 months after the surgery. Health status was measured by the Index of Well-Being. Costs of services for arthritis were determined by interview and billing records. Six months after TJR, significant improvements were seen in global health and in functional status. The average cost of care for the 6 months prior to TJR was $933. The average cost during the 6 months beginning with the TJR was $22,730 per patient--due almost entirely to costs of surgery. In general, the surgery did not change work status, probably because the mean age of the patients was 66.4 years. There were large effectiveness/cost differentials (the larger the effectiveness/cost differential, the higher the degree of cost-effectiveness [CE]). At 6 months, for all patients, the CE was associated with initial health status. The highest CE was observed in 10 patients who initially had the poorest health. TJR is more cost-effective for patients with the most to gain and less effective for those with better preoperative health status. PMID- 3091042 TI - Bacteriological and ultrastructural studies on the effect of subinhibitory beta lactam concentrations on intraphagocytic killing of Pseudomonas aeruginosa by human polymorphonuclear leukocytes. AB - The effect of azlocillin, ticarcillin and cefsulodin, respectively, on the susceptibility of Pseudomonas aeruginosa to the antimicrobial action of human polymorphonuclear leukocytes (PMN) was investigated under two different experimental conditions. Firstly, phagocytic capacity as well as bactericidal activity of PMN were assessed in a homologous system, i.e. the clinical isolate as well as the PMN and serum were obtained from the same patient. Secondly, ultrastructural studies were performed by electron microscopy. Preincubation of bacteria with subinhibitory beta-lactam concentrations augmented the phagocytic capacity as well as the antibacterial activity of PMN; azlocillin tended to be the most effective drug in this respect. The enhanced susceptibility to leukocyte killing is not due to an increased antibacterial action of the beta-lactams in the presence of PMN. These findings suggest that a non-immunological linkage between bacteria and PMN may exist which may be based on the interaction between bacterial- and eukaryotic surface structures, respectively. It may be assumed that the antipseudomonal beta-lactam antibiotics may cause changes in the surface structures of P. aeruginosa, thus rendering them more susceptible to phagocytosis. Preliminary data indicate that the lectins on the outer membrane of P. aeruginosa are not mannose sensitive. Electron microscopic studies revealed that azlocillin pretreatment of bacteria brought about a high undulation and a disruption of the outer membrane. These morphological changes may render bacteria more vulnerable to the antimicrobial action of PMN. It may be speculated that an interference with surface adhesins and induction of morphological changes may affect engulfment and intracellular killing of bacteria. PMID- 3091043 TI - Interaction between mesna and selected transition metals in vitro and in vivo. AB - The interactions between mercaptoethanesulphonic acid (mesna) and transition metal ions was investigated. Mesna was shown to react with selected transition metals (to form covalent metal thiol compounds) resulting in reduction of their oxidation state with the possible concomitant oxidation of mesna to dimesna. The reactions between mesna and copper were investigated in detail. Mesna is known to bind to serum albumin, copper was found to chemically combine with the mesna protein complex. Administration of copper to rats resulted in accumulation of copper in the kidney, while simultaneous administration of mesna and copper resulted in accumulation of copper in liver. The possible role of mesna-albumin complexes in copper transport is postulated and the importance of this in cancer treatment, where serum copper levels are often raised, is discussed. PMID- 3091044 TI - Radiographic comparison of plain films in second- and third-degree ankle sprains. AB - A literature search failed to demonstrate any investigations of the plain films of the ankle to determine whether there were any measurable differences in the ankle mortise, which would differentiate between a second and a third degree ankle sprain, thus obviating the need for stress views. In this study, the authors independently measured the distances between the talus and tibia at eight predetermined sites on the lateral and mortise views. This was done blindly so that neither author knew which cases were second- or third-degree ankle sprains. Only definite third-degree ankle sprains, as defined by a positive anterior drawer sign and/or a positive inversion stress test result on clinical evaluation, were included. The authors found there was severe interobserver variability. The authors thus feel that there is no clinically significant measurement on plain films of the ankle that can be used to differentiate accurately between second and third degree ankle sprains, and current reliance on clinical findings and subsequent stress x-ray films is appropriate and must remain the non-operative standard for evaluation of this problem. PMID- 3091045 TI - Accident modelling and economic evaluation. AB - This paper summarizes contributions to the IDBRA workshop made by Votey, Krupp and Jones-Lee. Votey set out the basic principles of costs and benefits as applied to accident control measures and discussed the various elements of effective economic analysis. Krupp presented information relating to the determination of the costs of injury accidents in the Federal Republic of Germany, and Jones-Lee discussed in more general terms the principle ways in which accident costs might be determined. The final section draws some general conclusions relating to the workshop as a whole. PMID- 3091046 TI - Learning impairments after 6-OHDA treatment: a comparison with the effects of thiamine deficiency. AB - Cortical norepinephrine, dopamine and 3,4-dihydroxyphenylacetic acid were reduced by injection of 6-hydroxydopamine (6-OHDA) jointly into the cisterna magna and the dorsal noradrenergic bundle. On subsequent behavioral testing, deficits were observed for spatial delayed alternation learning, but not for active or passive avoidance. Treatment with clonidine resulted in a significant improvement in spatial delayed alteration for experimental as compared to control animals. Injections of 6-OHDA into the cisterna magna alone had no significant effect on brain chemistry or behavioral measures. These results are similar to previous observations following a bout of thiamine deficiency, in which cortical catecholamines were depleted in animals that had exhibited deficits for spatial delayed alternation learning. We argue that the cortical catecholamine deficits observed in post-thiamine-deficient animals are sufficient to account for the delayed alternation deficits observed in this animal model of Korsakoff's psychosis. PMID- 3091047 TI - 6-Hydroxydopamine-induced turning behaviour in the rat: the significance of acetylcholinesterase in cerebrospinal fluid. AB - In the substantia nigra, acetylcholinesterase may have a novel function related not to cholinergic transmission, but to the homeostasis of dopaminergic nigrostriatal neurones. The initial aim of this study was thus to see whether, in the rat, release of the enzyme into cerebrospinal fluid would reflect turning behaviour following unilateral 6-hydroxydopamine lesions of varying severity. It was found that acetylcholinesterase levels, lower than those in the cerebrospinal fluid of control rats, were accompanied by marginal circling behaviour and a small loss of striatal dopamine: on the other hand, elevated acetylcholinesterase activity was observed in the cerebrospinal fluid of rats displaying vigorous turning behaviour and with large depletion of striatal dopamine. It has already been demonstrated that exogenous acetylcholinesterase, applied locally to nigral neurones, has both electrophysiological and behavioural effects reminiscent of dopamine agonists. Hence it is possible that exogenous acetylcholinesterase could modify turning behaviour resulting from unilateral striatal dopamine depletion. Purified acetylcholinesterase, administered by cisternal puncture, attenuated circling behaviour for up to 7 days. The possible mechanisms are discussed by which endogenous acetylcholinesterase in cerebrospinal fluid could serve as an index of dopamine depletion in the nigrostriatal pathway and how exogenous enzymes might alleviate the accompanying motor dysfunction. PMID- 3091048 TI - [Community disease, community prevention]. PMID- 3091049 TI - DNA-dependent RNA polymerases of the three orders of methanogens. AB - The DNA-dependent RNA polymerases of members of the three orders of methanogens were purified and their enzymatic properties described. The enzymes consist of 7 8 polypeptides. Although these differed in molecular mass, the four heaviest components could be allied to components of the enzyme of Methanobacterium thermoautotrophicum, W by cross-reaction with antibodies directed against the denatured polypeptides of this enzyme. The antisera against native RNA polymerases isolated from representatives of the different orders, on the other hand, gave rise to serological cross-reaction between different genera but not between different families and orders. These antisera are thus useful for taxonomic purposes. The RNA polymerase of the extreme thermophile Methanothermus fervidus shows a rather low thermostability. No factors having a stabilizing influence on the enzyme could be detected. PMID- 3091050 TI - Purification of glucoamylase by acarbose (BAY g-5421) affinity chromatography. AB - Aspergillus niger and Rhizopus sp. glucoamylases were purified on an affinity chromatography column from commercially available, impure enzyme preparations. Up to 2 mg of glucoamylase protein was bound without leakage to a 1-ml affinity gel column (0.7 X 2.5 cm) possessing a covalently linked acarbose ligand (1 mg acarbose/g wet gel), and the bound enzyme was specifically released by irrigation of the column with a solution of maltose. A complete cycle of purification was accomplished in about 8 h. Glucoamylases were recovered, in more than 80% yield, free of alpha-amylase activity and possessing specific activities comparable to those of preparations obtained by time-consuming, multistep procedures involving several ion-exchange and hydrophobic column fractionations. Thus, acarbose affinity chromatography provides a general method for the rapid and efficient purification of the glucoamylases, and seems to be ideally suited for scale-up for the commercial purification of these enzymes. PMID- 3091051 TI - A detailed examination of the iodination of beta-galactosidase: stoichiometric inactivation by nonspecific iodination. AB - The incorporation of 125I, using lactoperoxidase, and the subsequent inactivation of beta-galactosidase in the period when incorporation and inactivation were stoichiometric were investigated in detail. The high pressure liquid chromatographic (HPLC) radioactive profiles of the tryptic peptides of samples taken in the stoichiometric period showed that, although two labelled peptides predominated, there were other labelled peptides. The predominating peptides were shown to be the mono- and di-iodinated forms of the peptide containing Tyr-253. This confirmed the result of an earlier study, but quantitation showed that this iodination accounted for only 15-18% of the total. To show that the other labelled peptides in the HPLC profiles were not merely oxidized or partially digested forms of the peptide containing Tyr-253, two experiments were carried out. In one of the experiments, two of the other labelled peptides were isolated and identified as iodinated forms of the peptide containing Tyr-285 (5-7% of the incorporation). In the other experiment, four additional labelled fractions from the HPLC eluate were treated further with trypsin. No further digestion was observed and thus these peptides did not result from incomplete digestion of the sequence containing Tyr-253. Overall, these results show that, although the incorporation of 125I was stoichiometric with inactivation, no single Tyr was responsible for the inactivation as was tentatively suggested previously. The competitive inhibitor isopropyl-beta-D-thiogalactopyranoside (IPTG) was effective in reducing the rates of inactivation of the enzyme and incorporation of 125I, but the same peptides were labelled in the presence of IPTG as in its absence. PMID- 3091052 TI - [Statistical study of the radioimmunoassay radio-hormonal picture in the chronic anovulatory syndrome induced by exogenous opiates. 1) Analysis of basal hormone levels, and after stimulation with naloxone, LHRH, and TRH]. PMID- 3091054 TI - Paracetamol absorption from a feeding jejunostomy. AB - Disposition of paracetamol oral elixir was determined in two male patients after administration via feeding jejunostomy and compared with four male controls who received the same dose by mouth. Area under the plasma concentration-time curve, elimination half-life, and time to maximum concentration were similar in both groups after 650 mg paracetamol elixir. The absolute amounts and ratio of paracetamol glucuronide to sulphate, the major urinary metabolites after therapeutic paracetamol doses, were similar after jejunal administration as compared to oral administration. Paracetamol is absorbed and biotransformed in a similar manner after either jejunal or oral administration. Therefore, it may be administered effectively via jejunostomy tube in patients who require this route of administration. PMID- 3091053 TI - Hyperammonaemia and hepatotoxicity during chronic valproate therapy: enhancement by combination with other antiepileptic drugs. AB - Erythrocyte (ENH3) and plasma (PNH3) ammonia levels, liver function tests and plasma valproate concentration were measured in 81 epileptic patients, comprising three therapeutic groups: Group 1 (23 patients) received sodium valproate (VPA) monotherapy, group 2 (33 patients) received sodium valproate combined with phenytoin, carbamazepine, phenobarbitone and/or primidone and group 3 (25 patients) received one or more of these anti-epileptic drugs without sodium valproate. The mean ENH3 and PNH3 of patients in group 1 (41.1 +/- 30.7 mumol l-1 and 37.1 +/- 31.8 mumol l-1, respectively) and group 2 (44.5 +/- 21.3 and 37.6 +/ 21.4 mumol l-1, respectively) were significantly (P less than 0.01) higher than those in group 3 (28.7 +/- 10.6 and 21.5 +/- 7.8 mumol l-1, respectively) and the reference range (30.1 +/- 7.9 and 20.8 +/- 5.7 mumol l-1, respectively). Hyperammonaemia was more prevalent amongst patients in group 2, for both ENH3 (45.5%) and PNH3 (54.6%), than amongst patients in group 1 (30.4% and 52.2%, respectively) and group 3 (8% and 8%, respectively). There was a significant (P less than 0.05) positive correlation between plasma VPA and total bilirubin concentrations. Chronic VPA therapy was also associated with an increase in bilirubin concentrations measured on average four months apart. PMID- 3091055 TI - Comparison of transdermal nitrate and isosorbide dinitrate in chronic stable angina. AB - The effects of transdermal nitrate (TN) (Transiderm-Nitro TTS, Geigy Pharmaceuticals, one 10 cm2 patch daily) and oral isosorbide dinitrate (ISDN) (Sorbitrate, Stuart Pharmaceuticals, 10 mg three times daily) were compared in a group of 20 patients with chronic stable angina pectoris. Treadmill exercise duration was prolonged from a median time of 365 s to 428 s after ISDN (P less than 0.05), but was unchanged after TN. The difference between the active treatments was not significant. Weekly consumption of glyceryl trinitrate (GTN) increased during treatment with TN from a median value of 5.5 to 6.3 (P less than 0.05). A decrease was observed after ISDN (7.8 to 3.9, P = NS), and the difference between the drugs was significant (P less than 0.01). Systolic arterial pressure was significantly lower during the ISDN than during the TN treatment period in both the supine (135 +/- 5 vs 128 +/- 5 mm Hg; P less than 0.05) and standing positions (134 +/- 5 vs 122 +/- 5 mm Hg; P less than 0.05). No change in weekly attack rate, the degree of ST depression at angina on treadmill testing, or the number of episodes of ST depression recorded during a 24 h period by Holter monitoring was observed after either drug. In this study, an antianginal effect was demonstrated for ISDN but not for TN. It is suggested that the dose of TN may have been inadequate to demonstrate such an effect, and further studies using a higher dose schedule will be required. PMID- 3091056 TI - Characterization of seven human melanoma cell lines: melanogenesis and secretion of plasminogen activators. AB - Permanent cell lines (UCT-Mel 1 through 7) were established from biopsies of metastatic tissue taken from seven patients with malignant melanoma. Cells from these lines were all aneuploid and all grew as non-contact-inhibited, adherent monolayers. All of the lines, with the remarkable exception of UCT-Mel 6, formed tumours in nude mice, expressed the melanoma M-18 antigen and synthesized plasminogen activators exclusively of the tissue-type. UCT-Mel 6 cells were non tumourigenic, they lacked the M-18 antigen and they synthesized plasminogen activators exclusively of the urokinase type. UCT-Mel 1 and UCT-Mel 2 formed pigment in vitro and both of these lines showed an increase in pigment content and tyrosinase synthesis with increasing cell density. The rate of plasminogen activator released by UCT-Mel 1 and UCT-Mel 3 declined strikingly as the cells became confluent. Assuming that proteolytic activity is required for cell migration in vivo; that tyrosinase synthesis reflects expression of the differentiated phenotype and that melanoma cells retain some of the characteristics of neural crest cells, we suggest that the effects of confluence and close cell-cell contact provide a useful experimental counterpart for the study of normal neural crest all behaviour that is characterized by an inverse relationship between migration and a protease secretion on the one hand and pigmentation on the other. PMID- 3091057 TI - Acute generalized microvascular injury by activated complement and hypoxia: the basis of the adult respiratory distress syndrome and multiple organ failure? AB - It has been suggested that generalized endothelial damage and permeability changes, induced by prolonged activation of the complement system and ensuing release of lysosomal enzymes, prostaglandins and toxic oxygen products, underlie the genesis of the Adult Respiratory Distress Syndrome (ARDS) and Multiple Organ Failure (MOF). The effects in New Zealand white rabbits were investigated of a 4 h infusion of activated complement and its combination with a short hypoxic episode on respiratory function, leukocyte count, platelet count and morphology of the lungs, heart, liver, kidney and spleen. Prolonged activation of the complement system induced hyperventilation with respiratory alkalosis and hypocapnia, depletion of granulocytes (PMN), and a variable accumulation PMN in the capillaries of all organs examined, in combination with interstitial, and, in the liver, cellular oedema. Electron microscopy of the lungs revealed degranulation of PMN, endothelial swelling and widening of the alveolar septa. The combination of hypoxia and systemic complement activation appeared to aggravate this microvascular injury with the occurrence of protein rich alveolar oedema and haemorrhage in the lungs and accumulation of PMN debris containing macrophages in the spleen. The alterations in respiratory function and pulmonary morphology in these rabbits, imitate the clinical and morphological characteristics of the early phase of ARDS. The inflammatory reaction, found in all other organs examined, might represent the early phase of MOF. If so, ARDS and MOF -- clinically closely interconnected syndromes -- might be interpreted as manifestations of the same syndrome and as the clinical expression of an uncontrolled whole body inflammation. PMID- 3091058 TI - Recombinant interferon-gamma and chemotherapy with isoniazid and rifampicin in experimental murine tuberculosis. AB - Viable bacterial counts in the lungs and spleens of mice infected intravenously with Mycobacterium tuberculosis, strain H37Rv were reduced by intravenous recombinant murine interferon-gamma (IFN-gamma) 1000-5000 u, but not by 200 u. Reduction in counts was greatest when IFN-gamma was given 1 day before infection and was not increased by additional doses in the preceding 2 days. The effect was complete in 1 day and was not increased by successive doses during the next week. Giving IFN-gamma in multilamellar liposomes further reduced the spleen viable counts, but this appeared due to the liposomes themselves and not to encapsulation of IFN-gamma within them. Only a minimal reduction in organ viable counts, not statistically significant, occurred when IFN-gamma was given 5 days after infection. Although IFN-gamma alone and isoniazid 25 mg/kg alone reduced the organ viable counts, combined treatment with IFN-gamma and isoniazid was no more bactericidal than isoniazid alone. Similarly, the bactericidal activity of rifampicin 25 mg/kg was not increased by simultaneous administration of IFN gamma. There seems little likelihood that IFN-gamma would increase the efficacy of the early stages of the chemotherapy of tuberculosis. PMID- 3091060 TI - Secretion of plasminogen activator inhibitor by cultured human epidermal cells. AB - A conditioned medium from cultured human epidermal cells was observed to inhibit the activity of exogenous urokinase. By reverse fibrin autography after SDS polyacrylamide gel electrophoresis, a plasminogen activator inhibitor was detected with a molecular weight of 46,000. Using Mr 33,000 [125I]-labelled urokinase we observed the formation of an enzyme-ligand complex. The molecular weight of this complex was 79, 000. These results indicate that cultured human epidermal cells secrete a plasminogen activator inhibitor (urokinase inhibitor) with a molecular weight of 46,000. PMID- 3091059 TI - Assessment of thrombogenicity of activated and non-activated prothrombin concentrates in a rat model. AB - In vitro clotting activity of rats injected with different preparations of prothrombin concentrates was measured. Animals rendered deficient in vitamin K dependent coagulation factors by early coumadin (warfarin) pretreatment, followed by injections of concentrate preparations were also evaluated. Findings indicate a dose-related response in abnormal coagulation changes demonstrable with each preparation and lack of protection of intravascular coagulation by coumadin anticoagulation. Furthermore, a role for in vivo factor VII activation of haemostasis following concentrate administration could not be elicited. PMID- 3091061 TI - Plasminogen activator secreted by cultured human melanocytes. AB - A plasminogen activator (PA), Mr 72,000, was detected in conditioned medium from human melanocyte cultures by fibrin autography. The electrophoretic mobility was identical to that of tissue PA produced by Bowes melanoma cells. PA activity in human melanocyte culture medium was inhibited by anti-tissue PA IgG, but not by anti-urokinase IgG. Our results are the first to show that normal human melanocytes in culture secrete tissue plasminogen activator. PMID- 3091062 TI - Treatment of chronic discoid lupus erythematosus with an oral gold compound (auranofin). AB - Twenty-three patients with severe longstanding discoid lupus erythematosus, unresponsive to conventional treatments, were treated with oral gold in a multicentre open study. Nineteen patients showed clinical improvement and in four of these there was complete resolution of lesions. Adverse reactions were generally mild and self limiting. PMID- 3091063 TI - Experimental evidence that skin carcinogenesis is a multistep phenomenon. PMID- 3091064 TI - Follicle growth patterns and endocrinological abnormalities in infertile women with minor degrees of endometriosis. AB - Eighteen patients whose only demonstrable cause of infertility was a minor degree of endometriosis and whose partners were normal, were investigated prospectively for one menstrual cycle using ultrasonography and endocrine profiles. Twelve cycles appeared to be normal. A luteinized unruptured follicle (LUF) occurred in two cycles and one patient had a follicular cyst. In a further two patients there was inadequate or abnormal folliculogenesis whilst in the last patient the follicle ruptured prematurely. This study describes the variety of endocrinological abnormalities found in women with mild endometriosis, and concludes that, in this series at least, there is a low frequency of LUF. PMID- 3091065 TI - Follicular fluid alpha 1-antitrypsin--correlation with fertilizing capacity of oocytes. AB - Follicular fluid and serum concentrations of alpha-antitrypsin (alpha 1-AT) were determined by radial immunodiffusion in 72 samples obtained from 33 infertile women undergoing in-vitro fertilization and embryo transfer. A statistically significantly lower concentration of alpha 1-AT was found in follicular fluids from which mature oocytes were recovered (mean 1.52, SE 0.06 g/l) than in those yielding immature oocytes (mean 2.96, SE 0.22 g/l). There was also a significantly higher rate of fertilization (85%) for oocytes from follicular fluids with alpha 1-AT concentrations of less than or equal to 2.0 g/l than for those obtained when the alpha 1-AT concentration was greater than 2.0 g/l (only 25%). The mean follicular fluid alpha 1-AT concentration (1.52, SE 0.06 g/l) of follicles yielding mature oocytes was significantly lower than the relevant mean serum concentration (3.17, SE 0.10 g/l). There was, however, no significant difference between follicular and serum concentration of alpha 1-AT in the group yielding immature oocytes or in the serum concentrations between the different oocyte maturity groups. The measurement of follicular alpha 1-AT may be a useful adjunct in predicting which oocytes are mature and likely to be fertilized. PMID- 3091066 TI - Modulation of the sensitivity of chromatin to exogenous nucleases: implications for the apparent increased sensitivity of transcriptionally active genes. AB - We have examined the effects of changing the ionic composition of the buffers in which nuclei are isolated on the sensitivity of chromatin to micrococcal nuclease and deoxyribonuclease I. Unless nuclei are isolated in buffers containing physiological levels of monovalent (150 mM KCl) and divalent (2-5 mM MgCl2) cations, there is a substantial loss of higher order structure. The ionic composition of the buffer in which the digestion is carried out also affects the amount of material digested both by modulating higher order structure and by determining the solubility of the released material. Magnesium ion concentrations greater than 2 mM and calcium ions at virtually any concentration precipitate substantial amounts of the released chromatin fragments. These observations can be interpreted in light of the known effects of the ions on 10- and 30-nm fiber structure and used as a basis for improvements in techniques for isolating chromatin and for studying its structure and function using exogenous nuclease probes. The apparent nuclease sensitivity of transcriptionally active chromatin was reexamined and shown to be more likely a reflection of differential solubility rather than an overall increase in nuclease sensitivity. PMID- 3091067 TI - Kinetics of interaction of C1 inhibitor with complement C1s. AB - The kinetics of inhibition of the complement serine protease, C1s, by its only known inhibitor, C1 inhibitor, have been measured by a variety of methods. One method continuously monitors the loss of esterolytic activity with a synthetic substrate coupled to a chromogen while another monitors the formation of a stable (covalent) complex by high-pressure size-exclusion chromatography under dissociating conditions. Additional methods employ fluorescence probes to follow the formation of bimolecular complexes but are not expected to distinguish between covalent product and noncovalent (reversible) intermediates. There was good agreement between rate constants obtained by the various methods over a broad range of inhibitor concentrations, suggesting that noncovalent intermediates do not accumulate to a significant extent. The reaction appears to be pure second order with a bimolecular rate constant of 6.0 X 10(4) M-1 s-1 at 30 degrees C, independent of Ca2+, and an activation energy of 11.0 kcal/mol. The rate increases up to 35-fold in the presence of heparin which was shown to bind to all three components (enzyme, inhibitor, and complex) with similar affinity (Kd = 2.0-3.3 microM). The fluorescent probe 1,1'-bis(anilino)-4-,4' bi(naphthalene)-8,8'-disulfonate [bis(ANS)] bound to the complex with Kd = 0.26 microM under conditions where the individual components had little affinity for the dye, consistent with the generation of one or more hydrophobic binding sites on the protein surface during complex formation. PMID- 3091068 TI - An ordered addition, essential activation model of the tissue factor pathway of coagulation: evidence for a conformational cage. AB - One way in which coagulation may be initiated is by the action of factor VIIa (a plasma serine protease) and tissue factor (a membrane-bound lipid-dependent glycoprotein). We show that in the absence of either factor VIIa or tissue factor, the activation of the natural coagulation substrates, factors IX and X, is not detectable; i.e., tissue factor is an essential activator. We propose that the reaction is fully ordered; that is, the enzyme-activator complex picks up substrate to form a ternary product forming species. Our model precludes the formation of enzyme-substrate and activator-substrate complexes. We have derived equations for the two possible variations of this model: one in which product formation is accompanied by the release of the enzyme-activator complex and the other in which product, free enzyme, and free activator are formed with each catalytic cycle. Our data support only the former which is consistent with both steady-state and rapid equilibrium assumptions. The model is supported by experiments using a monoclonal anti-tissue factor antibody, which affects only the Km app, and a modified form of factor VIIa, which, depending on the sequence in which reagents are added to the reaction, either decreases the Vmax or increases the Km app. We present equations describing the initial velocity of these reactions. Utilizing dilution-jump experiments, we show that the system is hysteretic and suggest that this phenomenon is due to a slow release of enzyme from activator. However, the kinetically determined dissociation constant of enzyme and activator, previously found to be 4.5 nM under equilibrium conditions, was estimated to be 0.04-0.09 nM. Accordingly, we examined other essential activation models in which the product-forming species consists of a complex of enzyme, activator, and substrate at a molar ratio of 1:1:1; none could account for the apparent tight binding of enzyme and activator. We therefore postulate an ordered addition, essential activation model in which the enzyme undergoes two conformational transformations: one as a consequence of binding to tissue factor, resulting in a species which binds to and hydrolyzes its natural substrates. The other conformational change in the enzyme is induced by substrate, resulting in a species which binds more tightly to its activator. Thus, we hypothesize a "conformational cage" which precludes the dissociation of enzyme from activator while significant concentrations of substrate are present. PMID- 3091069 TI - Autocatalytic quinone methide formation from mitomycin c. AB - Mitomycin c in the presence of NADPH and brewers' yeast NADPH: (acceptor) oxidoreductase (Old Yellow enzyme, EC 1.6.99.1) is transformed, at pH 8.0 and with anaerobicity, to two major mitosene products (the cis- and trans-1-hydroxy 2,7-diaminomitosenes; respective yields of 45 and 30%). These arise by covalent trapping by solvent of a quinone methide intermediate, obtained by rearrangement of the mitomycin c hydroquinone. At lower pH (6.5), the major product of this reaction is 2,7-diaminomitosene, which arises by covalent trapping of the quinone methide by H+. In the former instance the quinone methide acts as an electrophile and in the latter as a nucleophile. A detailed kinetic analysis indicates that the role of the NADPH and Old Yellow enzyme is to initiate an autocatalytic reaction, propagated by mitomycin c reduction by the mitosene hydroquinones (arising by the electrophilic pathway). The evidence supporting this conclusion is the formation of oxidized mitosene products, under the rigorously anaerobic reaction circumstance, the nonstoichiometric participation of NADPH, a dependence of the velocity on the total mitomycin c concentration, the pH dependence of the reaction, and the accurate simulation of the overall kinetic course with a mathematical model of the autocatalytic pathway. These observations indicate that the autocatalytic pathway may be dominant during in vitro mitomycin c anaerobic reductive activation by other reducing agents and that (as with anthracycline reductive activation) oxidation of the mitosene hydroquinone obtained from nucleophile addition to the quinone methide may be a necessary event for the formation of stable covalent adducts in vivo. PMID- 3091071 TI - Purification and characterization of three distinct glutathione transferases from mouse liver. AB - Three distinct glutathione transferases in the liver cytosol fraction of male NMRI mice have been purified by affinity chromatography and fast protein liquid chromatofocusing. These enzymes account for approximately 95% of the activity detectable with 1-chloro-2,4-dinitrobenzene as electrophilic substrate. Differences between the three forms are manifested in isoelectric points, apparent subunit molecular mass values, amino acid compositions, N-terminal structures, substrate specificities, and sensitivities to inhibitors, as well as in reactions with specific antibodies raised against glutathione transferases from rat and human tissues. The results indicate strongly that the three mouse enzymes are products of different genes. A comparison of the mouse glutathione transferases with rat and human enzymes revealed similarities between the transferases from different species. Mouse glutathione transferases have been named on the basis of their respective subunit compositions. PMID- 3091072 TI - Time-course of altered islet phospholipids and of calcium binding and ionophoretic properties of islet lipids following glucose stimulation. AB - The time-course of alteration in islet cell phospholipid content following D glucose exposure in islet cells and in islet cell membranes was related to the ability of lipids extracted from both cultured pancreatic islet cells and from plasma membranes isolated from the islet cells to translocate calcium in two model membrane systems. The first model system (bulk-phase system) detected lipid species with the ability to bind calcium, irrespective of their ability to enhance calcium transport across cell membranes. The second system (multilamellar membrane system) detected lipid species with the ability to both bind calcium and to enhance calcium transport across cell membranes (true ionophores). Pre exposure to high D-glucose concentration led to a rapid (within 1 min) fall in membrane phosphoinositides. This was partially blocked by mannoheptulose. A concurrent fall in calcium binding activity of lipids from the plasma membrane was observed. In the whole islet cell fraction, D-glucose induced a marked increase in Ca2+ ionophoretic activity. Unlike the fall in membrane polyphosphoinositides and membrane Ca2+ binding activity, these changes were dependent on the presence of added extracellular calcium. L-Glucose was without effect on membrane phosphoinositide content. It is concluded that altered membrane and intracellular phospholipids may contribute to the increased availability of intracellular Ca2+ following D-glucose stimulation by virtue of their Ca2+ binding and ionophoretic properties. PMID- 3091070 TI - Effects of certain 5'-substituted adenosines on polyamine synthesis: selective inhibitors of spermine synthase. AB - A number of nucleosides related to S-adenosylmethionine were tested for their inhibitory action on three enzymes involved in the biosynthesis of polyamines. The particular objective of the experiments was to determine whether any of the compounds could be used as selective inhibitors of the synthesis of spermine by spermine synthase. None of the nucleosides examined were potent inhibitors of S adenosylmethionine decarboxylase. 5'-[(3-Aminopropyl)amino]-5'-deoxyadenosine dihydrochloride was quite a strong inhibitor of spermidine synthase (I50 of 7 microM) but was more than an order of magnitude less active than S-adenosyl-1,8 diamino-3-thiooctane, which is a mechanism-based inhibitor of this enzyme. 5'-[(3 Aminopropyl)amino]-5'-deoxyadenosine also inhibited spermine synthase with an I50 of 17 microM, but more selective inhibition of spermine synthase was produced by 9-[6(RS),8-diamino-5,6,7,8-tetradeoxy-beta-D-ribo-octofuranosyl]-9 H-purin-6- amine (I50 of 12 microM) and by dimethyl(5'-adenosyl)sulfonium perchlorate (I50 of 8 microM) since these compounds were much less active against spermidine synthase. Both 9-[6(RS),8-diamino-5,6,7,8-tetradeoxy-beta-D-ribo-octofuranosyl]-9 H-purin-6- amine and dimethyl(5'-adenosyl)sulfonium perchlorate were able to reduce the synthesis of spermine in SV-3T3 cells, but there was a compensatory increase in the concentration of spermidine, and there was no effect on cell growth. These results and those from experiments in which these spermine synthesis inhibitors were combined with inhibitors of spermidine synthase and ornithine decarboxylase indicated that the cells compensated for the inhibition of the aminopropyltransferases by increasing the production of decarboxylated S adenosylmethionine and putrescine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091073 TI - Tyrosine and tryptophan modification monitored by ultraviolet resonance Raman spectroscopy. AB - Nitration of tyrosine with tetranitromethane shifts the tyrosine absorption spectrum and abolishes its 200 nm-excited resonance Raman spectrum. There is no detectable resonance Raman contribution from either reactants or products. Likewise, modification of tryptophan with 2-hydroxy-5-nitrobenzyl bromide (HNBB) shifts its absorption spectrum and abolishes its 218 nm-excited resonance Raman spectrum. In this case resonance Raman bands due to HNBB are seen, but are readily distinguishable from the tryptophan spectrum, can be computer-subtracted. When stellacyanin was treated with tetranitromethane the UV resonance Raman spectrum was greatly attenuated; quantitation of the 850 cm-1 tyrosine band intensity gave a value of 4.3 tyrosines modified out of the seven present in stellacyanin, in good agreement with an estimate of 4.7 from the absorption spectrum. For cytochrome c, the resonance Raman spectrum indicates that two out of the four tyrosines are modified by tetranitromethane treatment, consistent with the crystal structure, which shows two buried tyrosines and two at the protein surface. Treatment of stellacyanin with HNBB gave a reduction in the tryptophan spectrum, excited at 218 nm, consistent with one of the three tryptophans being modified. These modification procedures should be useful in distinguishing spectra of buried tyrosine and tryptophan residues from those at the surface. PMID- 3091074 TI - Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. AB - The dimethylmethylene blue assay for sulphated glycosaminoglycans has found wide acceptance as a quick and simple method of measuring the sulphated glycosaminoglycan content of tissues and fluids. The available assay methods have lacked specificity for sulphated glycosaminoglycans in the presence of other polyanions, however, and have not discriminated between the different sulphated glycosaminoglycans. We now describe a modified form of the dimethylmethylene blue assay that has improved specificity for sulphated glycosaminoglycans, and we show that in conjunction with specific polysaccharidases, the dimethylmethylene blue assay can be used to quantitate individual sulphated glycosaminoglycans. PMID- 3091075 TI - Inhibition of bilirubin UDPglucuronosyltransferase activity by triphenylacetic acid and related compounds. AB - Bilirubin UDPglucuronosyltransferase of rat or human liver microsomes was inhibited, in vitro, by triphenylacetic acid and by structurally related arylcarboxylic acids. This inhibition appeared to be competitive towards bilirubin, and mixed-type towards UDPglucuronic acid. A decrease in the number of phenyl rings or the absence of the carboxyl group in the molecule gave structures which did not affect enzyme activity, showing that both the triphenyl moiety and the carboxyl group were necessary for the inhibition. On the other hand, successive additions of methylene groups in the aliphatic chain progressively increased inhibitory potency. Kappi,bilirubin for triphenylacetic acid was 96 microM compared with 5 microM for 7,7,7-triphenylheptanoic acid. The inhibition of bilirubin UDPglucuronosyltransferase was not due to displacement of bilirubin from albumin. On the basis of these results an attempt was made to delineate the molecular events leading to glucuronidation of bilirubin. PMID- 3091076 TI - Resistance to oxidative stress by hyperplastic and neoplastic rat liver tissue monitored in terms of production of unpolar and medium polar carbonyls. AB - The susceptibility of rat liver tissue to oxidative stress during its neoplastic transformation was analyzed by both qualitative and quantitative measurements of the carbonyl products of lipid peroxidation. Diethylnitrosamine was used as initiating agent of hepatocarcinogenesis and lipid peroxidation levels were monitored in the homogenates from normal liver, hyperplastic nodules and tumour, incubated in the presence or in the absence of ascorbate or adenosine diphosphate iron complex. While the basal levels of lipid peroxidation in the three experimental conditions were found to be quite similar, in the presence of the pro-oxidant stimulus a remarkable reduction in aldehyde production was shown not only by the hepatoma tissue but also by the preneoplastic nodules. PMID- 3091077 TI - The active and the inactive plasminogen activator inhibitor from human endothelial cell conditioned medium are immunologically and functionally related to each other. AB - In human endothelial cell conditioned medium a fast-acting inhibitor of tissue type plasminogen activator and urokinase has been detected. Moreover, an inactive inhibitor of these plasminogen activators is present, that can be activated by denaturing agents such as sodium dodecyl sulphate (SDS). The mutual relationship between these inhibitors was studied. The fast-acting plasminogen activator inhibitor from human endothelial cell conditioned medium was purified in a complex with tissue-type plasminogen activator by immune adsorption, using an immobilized anti-tissue-type plasminogen activator antibody. With the complex as an antigen, specific antibodies were raised against this inhibitor in rabbits. The antiserum immunoreacted with both the inactive and the fast-acting plasminogen activator inhibitor. Endothelial cell conditioned medium (containing the inactive plasminogen activator inhibitor) was treated with SDS and the inhibitory activity that emerged was purified. The SDS-generated product formed complexes with tissue-type plasminogen activator with the same molecular mass as those formed with the fast-acting inhibitor. Moreover, the inhibitory activity generated by SDS treatment showed the same kinetic behaviour with tissue-type plasminogen activator as did the fast-acting inhibitor. These data show that the fast-acting and the inactive plasminogen activator inhibitor are immunologically and functionally related to each other, and probably represent different molecular forms of the same protein. PMID- 3091078 TI - Differential effects of spermine on aggregation, inositol phosphate formation and protein phosphorylation in human platelets in response to thrombin, arachidonic acid and lysophosphatidic acid. AB - Platelet aggregation stimulated by thrombin, arachidonic acid or lysophosphatidic acid is associated with rapid phosphorylation of two platelet proteins, myosin light chain and a 47 kDa protein. The polyamine, spermine, inhibited platelet aggregation stimulated by all three agents. Spermine inhibited thrombin stimulated phosphorylation of myosin light chain and the 47 kDa proteins as well as thrombin-induced production of the inositol phosphates and phosphatidic acid. In contrast, spermine did not inhibit phosphorylation of either protein or the formation of inositol phosphates and phosphatidic acid in response to arachidonic acid or lysophosphatidic acid. Although spermine has been demonstrated to inhibit both phosphatidylinositol-specific phospholipase C and calcium-dependent protein kinases in cell free systems, these results suggest that, in the intact platelet, spermine does not directly inhibit these enzymes. Inhibition of aggregation stimulated by arachidonic acid and lysophosphatidic acid is secondary to interference with platelet-platelet interaction but not with platelet activation. In contrast, spermine inhibits thrombin-induced platelet activation. This thrombin-specific inhibition may be related to interference with the binding of thrombin to its receptor or to its catalytic substrate on the cell surface. PMID- 3091079 TI - Gossypol prevents activation of purified proenzyme of human seminal plasma acidic proteinase. AB - Gossypol inhibits the potential activity of the proenzyme form of human seminal plasma acidic proteinase, but has no effect on the active enzyme under the conditions tested. Inhibition of proenzyme is rapid and pH-dependent: 50% inhibition can be observed at gossypol concentrations of approx. 1.5 X 10(-5) M. SDS-polyacrylamide gel electrophoresis indicates that treatment of proenzyme with gossypol prevents the formation of active enzyme that normally occurs on acidification. Determination of free amino groups with 1-fluoro-2,4 dinitrobenzene suggests that gossypol reacts with 7.8 out of the 11.0 lysine residues in proenzyme: such a reaction could interfere with the activation process. PMID- 3091080 TI - Association of ferrochelatase with Complex I in bovine heart mitochondria. AB - The location of ferrochelatase in bovine heart mitochondria has been studied. When the mitochondria were fractionated into Complexes I, II and III, ferrochelatase activity was only found in Complex I. Complex I also showed heme synthesis from ferric ion in the presence of NADH as an electron donor. Immunoblot experiments confirmed the presence of ferrochelatase in Complex I, but not in Complexes II or III. Some phospholipids, including phosphatidylserine and cardiolipin, stimulated NADH-dependent heme synthesis from ferric ion. When purified ferrochelatase was incubated with the low molecular weight form of NADH dehydrogenase prepared from Complex I, heme synthesis from ferric ion occurred by the addition of NADH. FMN markedly elevated the synthesis. These results indicate that ferrous ion is produced by NADH oxidation in Complex I and is then utilized for heme synthesis by ferrochelatase. PMID- 3091081 TI - Regulation of hepatic glycogen phosphorylase and glycogen synthase by calcium and diacylglycerol. AB - Incubation of rat hepatocytes with angiotensin II (1 nM) produced a time dependent accumulation of 1, 2-diacylglycerol and inactivation of glycogen synthase with maximum effects at 10 min. The level of diacylglycerol then gradually declined and the activity of glycogen synthase I returned to control values at 30 min. In contrast, angiotensin II caused an increase in cytosolic Ca2+ and an activation of glycogen phosphorylase which were rapid and transient, reaching maximum values in less than 2 min and then returning to control levels at 15 min. There were excellent correlations between the changes in glycogen synthase I and diacylglycerol levels and between the changes in phosphorylase alpha and cytosolic Ca2+ in these time-course studies. However, there was no correlation between the changes in diacylglycerol and phosphorylase alpha or between the changes in cytosolic Ca2+ and glycogen synthase I. Norepinephrine also caused a slow increase in diacylglycerol and inactivation of glycogen synthase, and a rapid increase in cytosolic free Ca2+ and activation of glycogen phosphorylase. Addition of an alpha1-adrenergic blocker (prazosin or phentolamine) caused rapid decreases in cytosolic free Ca2+ and phosphorylase alpha, but only slowly reversed the inactivation of synthase and accumulation of diacylglycerol. The dose-response curves for norepinephrine and prazosin on glycogen synthase were well correlated with those on diacylglycerol. It is proposed that in liver cells, Ca2+-mobilizing hormones regulate phosphorylase a through a Ca2+-dependent mechanism and inactivate glycogen synthase through the generation of diacylglycerol, at least in part. The data provide additional support for the view that protein kinase C may be important in the regulation of glycogen synthase in liver. PMID- 3091082 TI - Action of TMB-8 (8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate) on cytoplasmic free calcium in adrenal glomerulosa cell. AB - To clarify the action of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB 8) on cellular calcium handling, changes in cytoplasmic free calcium concentration ([Ca2+]c) were studied in adrenal glomerulosa cell with a calcium sensitive photoprotein, aequorin. Results of our previous study demonstrate that 100 microM TMB-8 almost completely blocks aldosterone response to angiotensin II (Biochem. J. 232 (1985) 87-92). At 50 or 100 microM, TMB-8 decreased basal [Ca2+]c significantly; however, these doses of TMB-8 had little effect on an angiotensin-induced increase in [Ca2+]c. When angiotensin-induced calcium release from an intracellular pool(s) was assessed by measuring changes in [Ca2+]c in the presence of 1 microM extracellular Ca2+, 100 microM TMB-8 had little inhibitory effect on angiotensin-induced calcium release. A higher dose of TMB-8 (250 microM) slightly inhibited calcium release. Additionally, TMB-8 did not affect exogenous arachidonic acid-induced calcium release. In contrast, 50 microM TMB-8 markedly inhibited 8 mM potassium-induced increase in [Ca2+]c. These results indicate that a major action of TMB-8 on cellular calcium is an inhibition of calcium influx but not of calcium release. We suggest that TMB-8 should not be used as an 'inhibitor of calcium release'. PMID- 3091083 TI - Modulation of diphthamide synthesis by 5'-deoxy-5'-methylthioadenosine in murine lymphoma cells. AB - The histidine derivative diphthamide occurs uniquely in eukaryotic elongation factor 2 (EF-2), and is the specific target for the diphtheria toxin mono(ADP ribosyl)transferase. The first step in diphthamide biosynthesis may involve the transfer of aminocarboxypropyl moiety from S-adenosylmethionine to the imidazole ring of histidine in EF-2, to yield 2-(3-carboxy-3-aminopropyl)histidine and 5' deoxy-5'-methylthioadenosine (MeSAdo). As the possible nucleoside product of the initial reaction in the diphthamide biosynthetic pathway, MeSAdo could be an inhibitor of diphthamide formation. In the present experiments, we have analyzed the effects of MeSAdo on diphthamide synthesis in a MeSAdo phosphorylase deficient mutant murine lymphoma cell line (R1.1, clone H3). As measured by susceptibility to diphtheria toxin-induced ADP-ribosylation, MeSAdo inhibited the formation of diphthamide in EF-2. The inhibition was not due to a nonspecific effect on protein synthesis. Indeed, exogenous MeSAdo substantially protected the lymphoma cells from the lethal effects of diphtheria toxin. These results suggest that MeSAdo can specifically modulate the biosynthesis of diphthamide in EF-2 in murine malignant lymphoma cells. PMID- 3091084 TI - Multiple phosphorylation sites of rat liver glycogen synthase. AB - Rat liver glycogen synthase was purified to homogeneity by an improved procedure that yielded enzyme almost exclusively as a polypeptide of Mr 85,000. The phosphorylation of this enzyme by eight protein kinases was analyzed by cleavage of the enzyme subunit followed by mapping of the phosphopeptides using polyacrylamide gel electrophoresis in the presence of SDS, reverse-phase high performance liquid chromatography and thin-layer electrophoresis. Cyclic AMP dependent protein kinase, phosphorylase kinase, protein kinase C and the calmodulin-dependent protein kinase all phosphorylated the same small peptide (approx. 20 amino acids) located in a 14 kDa CNBr-fragment (CB-1). Calmodulin dependent protein kinase and protein kinase C also modified second sites in CB-1. A larger CNBr-fragment (CB-2) of approx. 28 kDa was the dominant site of action for casein kinases I and II, FA/GSK-3 and the heparin-activated protein kinase. The sites modified were all localized in a 14 kDa species generated by trypsin digestion. Further proteolysis with V8 proteinase indicated that FA/GSK-3 and the heparin-activated enzyme recognized the same smaller peptide within CB-2, which may also be phosphorylated by casein kinase 1. Casein kinase 1 also modified a distinct peptide, as did casein kinase II. The results lead us to suggest homology to the muscle enzyme with regard to CB-1 phosphorylation and the region recognized by FA/GSK-3, which in rabbit muscle is characterized by a high density of proline and serine residues. A striking difference with the muscle isozyme is the apparent lack of phosphorylations corresponding to the muscle sites 1a and 1b. These results provide further evidence for the presence of liver- and muscle specific glycogen synthase isozymes in the rat. That the isozymes differ subtly as to phosphorylation sites may provide a clue to the functional differences between the isozymes. PMID- 3091085 TI - Lipid-protein interactions in biomembranes studied through the phospholipid specificity of D-beta-hydroxybutyrate dehydrogenase. AB - Since the biological membranes are fundamental units in the living cells, the studies of lipid-protein interactions are crucial for the understanding of their structure, functions and properties. Beside hydrophobic interactions between fatty acids chain of phospholipids and intrinsic membrane proteins, the interactions between charged groups of the protein with the polar heads of phospholipids generally confer the specificity which may be absolute or preferential. This paper reports essential results obtained these last few years with D-beta-hydroxybutyrate dehydrogenase (BDH) from inner mitochondrial membrane, one of the most interesting and best documented examples of a lipid requiring enzyme. This is a review of the molecular basis--knowledge and strategy of study--of the lipid specificity for membrane protein functions. PMID- 3091086 TI - Prokaryotic gene expression in vitro: transcription-translation coupled systems. AB - Transcription-translation coupled systems have been developed to study prokaryotic gene expression. Several types of expression system have been described. The original system consists of a crude unfractionated Escherichia coli extract, which supports protein synthesis directed by a template DNA. Control of gene expression at the transcriptional stage has been studied using this unfractionated system. In this respect, two examples of particular interest, lactose and tryptophan operons, are described. Other systems are either partially reconstituted or highly defined, containing up to 30 purified factors necessary for transcription (RNA polymerase) and translation (aminoacyl-tRNA synthetases, initiation, elongation and release factors). Additional differences between the various systems relate to the analysis of the gene products. Whereas most methods involve analysis of the totally synthesized protein, a particular system implies the formation of only the N-terminal di- or tripeptide of the gene product. Reconstituted systems have proved useful in studies on transcriptional, e.g., discovery and role of L factor, as well as translational regulation of gene expression, e.g., autogenous control of ribosomal protein synthesis. PMID- 3091087 TI - Estimation of compartmentation of lysine inside the cells of Yarrowia lipolytica. AB - We studied the compartmentation of lysine in vivo by the tracer method of Subramanian et al. (J. Bacteriol. 115 (1973) 284-290). To calculate the size of the different lysine pools and lysine fluxes inside the cell, a mathematical model was designed enabling quantitative estimation of these data from experimental measurements. This technique was applied to a lysine-accumulating strain, 15901.7, and to its low lysine pool derivatives, ply-1, ply-4 and ply-9, which were selected for their low polyphosphate pools. In the mother strain, 15901.7, it appeared that lysine was stored mainly in a non-cytoplasmic compartment. In the mutants, the efflux from this compartment was higher and accounted for the higher percentage of lysine in the cytoplasm of these strains. Simulation with calculated parameters fitted the experimental curves very well. This was good evidence for the pertinence of the model. The biological significance of these results are discussed. PMID- 3091088 TI - Phosphorus-31 nuclear magnetic resonance study of post mortem catabolism and intracellular pH in intact excised rabbit muscle. AB - Phosphorus-31 nuclear magnetic resonance has been used to study the post mortem catabolism of high-energy phosphate compounds and the associated intracellular pH variation in pure fast- and slow-twitch rabbit muscles and in rabbit muscle with mixed fiber types. Comparative results from pure fiber types are reported for the first time. Large amounts of glycerophosphorylcholine (14.1 mumol/g fresh tissue) are found in the internal conoidal bundle (ICB), a pure oxidative slow twitch muscle, whereas the m. psoas major (PM), a pure glycolytic fast twitch muscle and the m. gastrocnemius caput medialis (GCM), with mixed fiber types, are devoid of the same metabolite. The total content of phosphorylated metabolites is constant among the three muscle types. The time-dependent post mortem changes in phosphorylated metabolites display the expected rapid drop in phosphocreatine and a simultaneous increase in intracellular inorganic phosphate. However, the ATP level remains constant during more than 2 h. Rate constants for metabolite breakdown and apparent ATPase activity have been determined. The comparative kinetics of intracellular acidosis at 25 degrees C yield rates of 3.3 X 10(-3) pH unit/min for PM, 2.7 X 10(-3) pH unit/min for GCM and 3.0 X 10(-3) pH unit/min for ICB. Initial intracellular pH values are 7.07, 7.20 and 7.02, respectively. Upon aging, the heterogeneity of the Pi signal reflects the existence of cellular compartments with different internal pH. The results suggest that the more intense low-pH Pi signal arises from the sarcoplasmic reticulum while the less intense resonance would reflect the sarcoplasmic higher pH. The temperature effect on post mortem catabolism in the 15-25 degrees C range has been documented. As expected, phosphocreatine and ATP breakdown increase with temperature but at a higher rate for slow-twitch ICB than for fast-twitch PM. PMID- 3091090 TI - Influence of beta,gamma-methyleneadenosine 5'-triphosphate and 2-phosphoglycerate on rat liver phosphoglycerate kinase. AB - The inhibitory action on rat liver phosphoglycerate kinase of structural analogs of the two substrates of this enzyme (beta,gamma- methyleneadenosine 5' triphosphate for ATP and 2-phosphoglycerate for 3-phosphoglycerate) was studied. In the direction of ADP utilization, the inhibition patterns obtained with beta,gamma-methyleneadenosine 5'-triphosphate are compatible with the reaction mechanism proposed previously (Lavoinne, A., Marchand, J.C., Chedeville, A. & Matray, F. (1983) Biochimie 65, 211-220). In the direction of ATP utilization, the normally observed nonlinear kinetics were changed into linear kinetics in the presence of these substrate analogs. Our results suggest that saturation of the substrate sites induces a conformational change of the enzyme. PMID- 3091089 TI - Glutathione status during the mitogenic response of rat splenocytes. Effects of oxygen concentration: FO2 21% versus FO2 7%. AB - Glutathione is known to be an important parameter for ConA proliferative response of murine splenocytes. We studied the glutathione status of ConA-stimulated rat splenocytes during the early and late phase of the mitogenic response under low (FO2 7%) and standard (FO2 21%) oxygen concentrations. We determined the intracellular total, oxidized and reduced glutathione levels after 6, 12, 24 and 48 h of culture with or without ConA and/or 2-ME, under FO2 7% and 21%. Our results showed that: The 2 GSSG/GSH + 2 GSSG ratio, which indicated the redox state of the cells, remained normal during the early period of culture (0-24 h), irrespective of culture conditions. After 48 h of culture, this ratio increased dramatically under FO2 21% and less under FO2 7%. The maintenance of the redox state seems to be an oxygen concentration-dependent phenomenon. ConA stimulation involved a glutathione consumption during the early stages of culture; under these conditions 2-ME increased the glutathione synthesis, which was higher under FO2 7% than under FO2 21%. On the other hand, the presence of 2-ME involved an increase of tritiated thymidine uptake in stimulated splenocytes, which was significantly higher under FO2 21% than under FO2 7%. Low oxygen tension (FO2 7%) can induce a higher increase of glutathione synthesis, whereas the respective ConA proliferative response is lower than that observed under standard O2 conditions. PMID- 3091091 TI - [Role of acetate and butyrate in the induction of NADH: rubredoxin oxidoreductase in Clostridium acetobutylicum]. AB - Study of the biosynthesis of NADH: rubredoxin oxidoreductase in resting cells of Clostridium acetobutylicum shows that this enzyme is synthesized at a maximal rate in the presence of acetic acid at a concentration of 3 g . l-1 and at pH 4.8. Protons do not play any role in this biosynthesis since no induction is observed in a medium without acetate for the same values of pH. Butyric acid at a concentration of 0.5 g . l-1 gives 50% induction and formic acid, isobutyric acid and propionic acid have no inductive action on NADH: rubredoxin oxidoreductase. These results are confirmed by studies using a dialysis bag. Only a culture against acetic acid at an initial concentration of 2 g . l-1 gives maximal biosynthesis of the enzyme, whereas a culture in which all products of metabolism are eliminated gives an activity which is 80% lower. PMID- 3091092 TI - Rapid separation of Escherichia coli 30S ribosomal proteins by fast protein liquid chromatography (FPLC). AB - The proteins of the 30S ribosomal subunit from Escherichia coli have been separated by reverse-phase high-performance liquid chromatography on a short alkyl chain (C1/C8)-coated phase. The reverse-phase column was connected to a fast protein liquid chromatography (FPLC) system. The 21 proteins of the 30S ribosomal subunit were resolved into 16 peaks. Eleven proteins were isolated in purified form in a single chromatographic run as shown by polyacrylamide gel electrophoresis and amino acid analysis. Interestingly, the retention times of some proteins differed from the retention times observed on other reversed-phase support materials. The results show the speed and resolution of reverse-phase FPLC for both analytical and semi-preparative separations of 30S ribosomal proteins. PMID- 3091093 TI - Vitamin-D dependent 9 kDa calcium-binding protein gene: cDNA cloning, mRNA distribution and regulation. AB - Cholecalciferol (calcitriol) the active hormonal form of vitamin D induces the synthesis of at least two intracellular calcium-binding proteins (Ka = 10(6) M 1), the cholecalcins (CaBP) in mammals. We used the synthesis of these proteins to study the genomic steroid-like action of vitamin D. The 9 kDa CaBP is mainly concentrated in the duodenum while 28 kDa CaBP is located in the kidney and cerebellum. Complementary DNA copies of rat intestinal 9 kDa CaBP mRNA were cloned in E. coli. The deduced amino acid sequence for 9 kDa CaBP contains two 'EF hand' domains corresponding to calcium-binding sites I and II. The homology observed suggests, after comparison with the structures of other intracellular CaBPs, that rat 9 kDa CaBP mRNA contains the remains of an untranslated calcium binding site III-like structure seen in 28 kDa CaBP from kidney and cerebellum of rat. Northern blots showed that the cDNA sequence hybridizes to a homogeneous 500 600 nucleotide mRNA species from rat duodenum. Larger mRNA species encoding 28 kDa CaBP were undetectable in rat kidney and cerebellum even under low stringency conditions. These findings demonstrate that there is no cross-hybridization between 9 kDa and 28 kDa CaBP mRNAs, and Southern analysis indicates that there are distinct genes coding for each rat cholecalcin. The cDNA probe was used to analyze the specific 9 kDa CaBP gene expression along the intestine of growing rats and during gestation and fetal development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091094 TI - In vitro RNA synthesis by viruses isolated from the yeast Yarrowia lipolytica. AB - Viruses isolated from the yeast Yarrowia lipolytica possess a DNA-independent RNA polymerase activity which is inhibited by ethidium bromide and by sodium pyrophosphate but not by actinomycin D. RNA synthesis is maximum at pH 8.0 and at 30 degrees C. Newly synthesized RNA molecules are largely released from the particles, are single-stranded and are able to hybridize with denatured viral genomic RNA. PMID- 3091095 TI - Serum diamine oxidase in the neonate. AB - Serum diamine oxidase (DAO) activities were measured in 9 pregnant women and in 33 neonates during the 1st week of life. The radiometric method was used. Very high values were found in the mothers (mean +/- SE: 720 +/- 143 pmol ml-1 h-1). Neonates showed significantly elevated values (mean +/- SE: 178 +/- 54 pmol ml-1 h-1) on the 1st postnatal day when compared to the 7th day values (mean +/- SE: 27 +/- 5.7 pmol ml-1 h-1). Serial determinations showed a progressive decline from day 1 to day 7 after birth. We suggest the high serum DAO levels in neonates during the first days of life are due to leakage of placental enzyme into the circulation either at birth or during fetal life. Consequently, serum DAO cannot be used as a marker of small bowel functional integrity in the 1st postnatal week. PMID- 3091096 TI - Determinants of resting regional cerebral blood flow in normal subjects. AB - Study of brain function via cerebral blood flow and metabolism measurements is believed to be of considerable significance in psychiatry. The present study examined the factors that determined patterns of regional cerebral blood flow (CBF) in 140 physically and mentally healthy, drug-free volunteers under resting conditions. Age, sex, and end-tidal CO2 levels were identified as the most powerful determinants of CBF, in that order. Age-related CBF reduction was found to be most marked in the frontal region. Women had higher CBF than men, and the difference was most obvious in the frontal region. The correlations between CO2 and CBF showed less striking, but significant, regional variations. Hematocrit was found to exert only minimal influence in the control of resting CBF. PMID- 3091097 TI - A two-year double-blind crossover trial of the prophylactic effect of methylene blue in manic-depressive psychosis. AB - A 2-year prophylactic trial was carried out in 31 bipolar manic-depressive subjects, comparing 300 mg/day methylene blue on a double-blind crossover basis with 15 mg/day. All patients were also maintained on lithium. Seventeen patients completed the 2-year trial. During the year the patients were treated with methylene blue at 300 mg/day, they were significantly less depressed than during the year on 15 mg/day. No significant difference in the severity of manic symptoms was shown. The trial had obvious limitations, e.g., a small number of subjects, a relatively large number of dropouts, relatively simple rating scales, doubts about blindness, and uncertainty as to whether or not 15 mg methylene blue per day could be considered a placebo. However, the results suggest that methylene blue may be a useful addition to lithium in the long-term treatment of manic-depressive psychosis and warrants further investigation. PMID- 3091098 TI - Serine and folate metabolism in fibroblasts from episodic psychotic patients with psychedelic symptoms. AB - A disturbance of serine-glycine metabolism in a group of patients who became psychotic after oral intake of serine may be due to any serine-related enzyme abnormality. In order to elucidate this problem, we studied several enzymes in fibroblasts obtained from these patients. First, the enzyme serine hydroxymethyltransferase was investigated. The apparent Km values for serine, L tetrahydrofolate (H4folate), and pyridoxal 5'-phosphate, as well as the maximal velocities of the forward and backward reactions measured in fibroblasts obtained from patients, were not different from those in the cells from controls. We also measured the activities of another three enzymes of the folic acid cycle, viz., 5,10-methylene-H4folate dehydrogenase, 10-formyl-H4folate synthetase, and 5,10 methenyl-H4folate cyclohydrolase, as well as the enzyme cystathionine beta synthase. Again, no differences were found among these enzymes in fibroblasts from patients and controls. It can be concluded that the psychotic symptoms occurring after the administration of serine are not the result of any malfunctioning of the enzymes investigated. PMID- 3091099 TI - Prolactin response to TRH in Alzheimer's disease and elderly controls. PMID- 3091101 TI - Glycosidases in cultured rat epididymal cells: enzyme activity, synthesis and secretion. AB - During transit through the epididymis, spermatozoa acquire fertilizing the cell surface exhibits an altered glycoprotein pattern. Epididymal cells and their secretions contribute to these sperm-surface changes. To examine this process, epithelial cells from rat caput and cauda epididymidis were cultured and examined for the synthesis, processing and secretion of two glycoprotein-modifying enzymes, beta-galactosidase and beta-glucuronidase. Cells were cultured four days, incubated with D-2-[3H] mannose and L-[35S] methionine, and placed in isotope-free media. Levels of both cellular and secreted beta-galactosidase and beta-glucuronidase were determined by immunoprecipitation of cell homogenates or medium, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and scintillation counting of bands. During a 1-h pulse, both caput and cauda cells synthesize two precursor forms of beta-galactosidase (Mr = 84,000 and 87,000), which are processed to the mature (Mr = 63,000) enzyme during a 24-h chase. Caput cells release a high molecular weight (HMW) form (Mr = 90-100,000) and mature beta-galactosidase into the media, but not the Mr = 84-87,000 precursor. On the other hand, cauda cells release mostly mature beta galactosidase. Ratios of radiolabeled mannose/methionine demonstrate a 7-fold greater mannose content in the cellular precursor of beta-galactosidase than in total protein. Another glycosidase, beta-glucuronidase, is synthesized as a Mr = 78,000-precursor which is processed to the mature Mr = 72,000 form. Medium in which caput and cauda cells were cultured contains both mature enzyme and a Mr = 94,000 form, but no 78,000-precursor form. Ratios of radiolabeled mannose/methionine in the cellular precursor of beta-glucuronidase are 2-fold greater than ratios in the total glycoprotein. Secretion is the major pathway of turnover for several epididymal glycosidases, since more than 50% of the total is secreted/day. These results indicate that cultured epithelial cells from the epididymis synthesize glycosidases and that processing and release differ, depending on the enzyme and the epididymal segment from which the epithelial cells were isolated. PMID- 3091100 TI - Acid phosphatases in germinal and somatic cells of the testes. AB - Four forms of acid phosphatase have been found in the testicular tissue of many mammalian species, but their exact cellular site has remained obscure. In this work, acid phosphatases have been studied in different reproductive organs of the male rat, in somatic cell lines derived by cloning from both rat and mouse testes, in primary cultures of rat Sertoli cells, and in isolated spermatogenic cells of the mouse. Among the reproductive organs, preputial glands show the highest specific activities with p-nitrophenyl phosphate as substrate, followed by the testicular tissue and the different regions of the epididymis. By contrast to that in other tissues, testicular activity with p-nitrophenyl phosphate is not influenced by tartrate and is activated markedly by cobalt (Co2+). Among the somatic cell lines, the highest hydrolysis rates are obtained with naphthyl substrates in the epithelial (TR-1) and myoid (TR-M) cell lines and marginally lower rates in the Leydig (TM3) and Sertoli (TM4) cell lines. With thymolphthalein phosphate, the latter two cell lines show very low activity. These activities are not influenced by different hormones and growth factors in the culture medium. The most marked Co2+-activated reaction with p-nitrophenyl phosphate is found in advanced stages of germinal cells and residual bodies. Primary cultures of Sertoli cells, prepared from rats 10 to 30 days of age, show a slight decrease in acid phosphatase levels; however, the activities are not influenced markedly by addition of follicle-stimulating hormone (FSH) and/or testosterone to the culture medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091102 TI - Inhibin fractionation: a comparison of human and porcine follicular fluid, with particular reference to protease activation. AB - A novel treatment has been devised in our studies of the purification of inhibin from porcine and human follicular fluids (pFFl and hFFl, respectively). Both pFFl and hFFl were precipitated with acetone and extracted with acetic acid to provide a starting material for subsequent gel filtration and reverse-phase high-pressure liquid chromatography (HPLC). Inhibin from pFFl was purified 4200-fold using this methodology. Inhibin from hFFl could not be purified to this degree since recoveries were relatively poorer than for pFFl and yielded too little material for the HPLC step. In our fractionation scheme, protease activities were assessed with a gel electrophoresis assay system. Protease activity at approximately 90 kDa was observed in raw pFFl. When inhibin was fractionated by extraction or chromatography, additional bands of protease activity appeared near 150 kDa, 66 kDa and at less than 45 kDa. In raw hFFl, only faint bands of protease activity were observed at approximately 90 kDa and at 85-90 kDa. Upon further fractionation of hFFl, protease activity was reduced below the ability of this method to detect it. Our results suggest that, with our treatment of follicular fluid, protease activity is present in pFFl and additional protease activity appears upon fractionation; proteases, although present, do not eliminate the possibility of obtaining a highly purified inhibin preparation with acceptable recoveries of inhibin activity during purification; and although protease activity could be reduced or eliminated from hFFl, the low yields of inhibin activity from this method mandate a different approach to purification of inhibin from hFFl. PMID- 3091103 TI - Synergism between granulosa and theca-interstitial cells in estrogen biosynthesis by gonadotropin-treated rat ovaries: studies on the two-cell, two-gonadotropin hypothesis using steroid antisera. AB - In mammalian ovaries, luteinizing hormone (LH) induces androgen biosynthesis by theca interna cells, whereas both follicle-stimulating hormone (FSH) and LH stimulate aromatase activity by granulosa cells. The joint action of these two types of cell and pituitary hormones forms the basis of a 2-cell, 2-gonadotropin hypothesis for biosynthesis of estrogen. We tested the synergism between these cell types using antisera against the estrogen precursors progesterone and testosterone. Ovaries were obtained from immature rats two days after a single injection of pregnant mare serum gonadotropin (PMSG). Granulosa cells were obtained by puncturing the follicles, and ovarian remnants were dissociated with collagenase to derive cells from the theca interstitium. Granulosa and theca interstitial cells were cultured alone or in combination for 20 h. Granulosa cells secreted negligible amounts of estrogen and testosterone, but contained high aromatase activity. Treatment with both FSH and human chorionic gonadotropin (hCG) increased production of progesterone in granulosa cells. In contrast, theca interstitial cells had negligible aromatase activity. Treatment with hCG, but not FSH, increased androgen production by theca interstitium; the hCG action was further augmented by the inclusion of exogenous progesterone. Furthermore, co culture of gonadotropin-treated granulosa and theca interstitial cells resulted in substantial increases in estrogen production, indicating synergism between the two types of cell. The increases in estrogen production in the co-cultures were accompanied by decreases in progesterone content. To test the possibility that progesterone released by granulosa cells may serve as a substrate for production of androgen in theca cells, specific antiserum was used to adsorb progesterone present in the medium. Addition of the progesterone antibody inhibited gonadotropin-stimulated production of testosterone (39% decrease) and estrogen (64% decrease) by the combined cell cultures. The inhibitory effect on estrogen production could be reversed by the addition of progesterone (10(-6) M) or testosterone (10(-6) M) but not by the addition of a synthetic progestin, R5020. Since testosterone released from theca cells may serve as the substrate for aromatases in granulosa cells, specific testosterone antiserum was also used. Production of estrogens by the combined cell cultures was inhibited (78%) by the testosterone antiserum, but the inhibitory effect was completely reversed by exogenous testosterone or progesterone. Thus, synergistic interactions between granulosa and theca interstitial cells are important in effecting maximal estrogen biosynthesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3091104 TI - Measurement of inhibin and an index of inhibin production by rat testes during postnatal development. AB - Our previous studies have shown that inhibin activity in rat testes can be measured using an in vitro inhibin bioassay. In animals that have undergone unilateral efferent duct ligation (EDL), the difference in inhibin content between the ligated and nonligated testis can be used as an index of the rate of inhibin production in vivo. In the present study we examined postnatal changes in inhibin content in the testes, and the production rates of inhibin and seminiferous tubule fluid in groups of neonatal, immature, and adult rats from 1 to 80 days old. We detected inhibin activity in testes of 1-day-old rats; the activity level rose linearly to Day 8, subsequently increasing markedly from Day 30 until it reached a plateau at Day 45. Increments in the content of inhibin and weight of the testis after unilateral EDL, interpreted to represent production of inhibin and seminiferous tubule fluid, commenced at Day 20 and increased rapidly between Days 30 and 50, decreasing thereafter to Day 80. The increase in content and production of inhibin was directly correlated to the rise in serum follicle stimulating hormone (FSH) and testosterone, suggesting that these two hormones are important in controlling inhibin secretion. In addition, the changes in serum FSH from the high, postnatal levels to those typical of adults were inversely correlated to the content and production rate inhibin in the testes and concentrations of testosterone in the serum. These data support the hypothesis that inhibin is specifically involved in the feedback control of pituitary FSH secretion during postnatal development, although a role for testosterone or a synergistic interaction between the two hormones cannot be excluded. PMID- 3091105 TI - The effects of food restriction and hypophysectomy on numbers of primordial follicles and concentrations of hormones in rats. AB - Three experiments were done to examine the effects of food restriction, beginning at 21 days of age, on loss of primordial follicles and on concentrations of gonadotropins and sex steroids in rats. In Experiment 1, food restriction (FR) from 21 to 51-55 days of age had no effect on number of primordial follicles, but increased the plasma concentration (p less than 0.05) of follicle stimulating hormone (FSH). (p less than 0.05). In Experiment 2, comparisons were made of groups of rats (1) fed ad libitum (AL) (2) hypophysectomized at 21 days of age and fed ad libitum (AL-HY), (3) food restriction from 21 to 52-58 days of age (FR), and (4) food restriction with twice-daily injections of follicular fluid (FR-FF). Hypophysectomy was the only treatment that decreased the loss of primordial follicles (p less than 0.001). Concentrations of FSH were decreased in AL-HY and increased in FR and FR-FF rats (144 +/- 13, 53 +/- 15, 275 +/- 30 and 359 +/- 56 ng/ml in AL, AL-HY, FR and FR-FF rats, respectively). Concentrations of luteinizing hormone (LH) were lower (p less than 0.05) in AL-HY, FR and FR-FF rats than in AL rats. In Experiment 3, AL and FR rats were unilaterally ovariectomized (ULO) at 30 days of age. Blood samples were taken 5 days prior to ULO, at ULO and at 12 h, 5 days, and 22-28 days after ULO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091106 TI - Prolactin modulates steroidogenesis by rat granulosa cells: I. Effects on progesterone. AB - Either testosterone or follicle-stimulating hormone (FSH) stimulates progesterone secretion by granulosa cells from rats but the combination of the two hormones increases progesterone production in a synergistic manner. We have investigated the effects of graded doses of prolactin (0, 0.02, 0.2, 2, or 10 micrograms/ml) alone or in combination with testosterone (0.5 microM), FSH (300 ng/ml), or FSH + testosterone on progesterone secretion by granulosa cells at two stages of differentiation. Relatively undifferentiated granulosa cells from immature, diethylstilbestrol-treated, hypophysectomized (HPX) rats were cultured in defined (serum-free) medium for 3 days. More highly differentiated granulosa cells were obtained on the morning of proestrus from the preovulatory follicles of 30-day old rats induced to undergo an estrous cycle by injection with 4 IU pregnant mare's serum gonadotropin; these cells were cultured in medium containing 10% fetal bovine serum. Prolactin alone did not enhance the negligible secretion of progesterone by cells from HPX rats, but increased progesterone secretion by cells from proestrous rats. Prolactin significantly enhanced the stimulatory effects of testosterone or FSH alone on cells from both HPX and proestrous rats. When cultures containing both FSH + testosterone were treated with prolactin, progesterone secretion by cells from proestrous rats was significantly enhanced, whereas secretion by cells from HPX rats was significantly depressed. Therefore when cells from HPX rats were cultured with both FSH and testosterone, the direction of the effect of prolactin was reversed from that observed with prolactin + FSH or testosterone alone, and from that observed when cells from proestrous rats were cultured with prolactin + FSH + testosterone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091107 TI - Prolactin modulates steroidogenesis by rat granulosa cells: II. Effects on estradiol. AB - The effects of prolactin on secretion of estradiol by rat granulosa cells obtained at two stages of differentiation and cultured under various conditions were determined. Relatively undifferentiated granulosa cells were obtained from immature, diethylstilbestrol-treated, hypophysectomized (HPX) rats and cultured in serum-free medium or with 10% serum. More highly differentiated granulosa cells were obtained on the morning of proestrous from the preovulatory follicles of immature rats in which an estrous cycle had been induced with 4 IU pregnant mare's serum gonadotropin; these cells were cultured in medium containing 10% serum. Cells were cultured for 3 days with graded doses of prolactin (0, 0.02, 0.2, 2, or 10 micrograms/ml) alone or in combination with follicle-stimulating hormone (FSH; 300 ng/ml), testosterone (0.5 microM), or FSH + testosterone. In control cultures (no prolactin) the relatively undifferentiated granulosa cells from HPX rats secreted negligible quantities of estradiol except when both FSH and testosterone were supplied. Prolactin alone or in combination with FSH or testosterone had no effect on estradiol secretion, but prolactin in combination with FSH + testosterone significantly decreased secretion in a dose-dependent fashion. This set of prolactin treatments was applied in both serum-free medium and medium containing 10% serum, with similar results under both culture conditions. The inhibitory effects of prolactin appeared to be reversible if cells were cultured with prolactin for only 1 day, but were not reversed if cells were cultured with prolactin for 2 or 3 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091108 TI - Glutaraldehyde treated bovine fibrocartilage arthroplasty for the scaphoid: a case history and discussion. AB - Avascular necrosis of the proximal pole of the carpal scaphoid following fracture often leads to degeneration and carpal collapse. Replacement arthroplasty as a treatment for this condition using a variety of materials has not been universally successful. A case is described in which a new arthroplasty material glutaraldehyde treated bovine fibrocartilage-was used as a spacer to restore carpal height. PMID- 3091109 TI - A measure of 2 x 2 association with stable variance and approximately normal small-sample distribution: planning cost-effective studies. AB - A measure of 2 x 2 association, Z, is developed having the property that n(Z - Z) has approximately a standard normal distribution, even for quite small sample size. Examples of the use of this variance-stabilizing and normalizing transformation in planning studies of 2 x 2 association are presented. Studies of the association between coronary artery disease and exercise stress test results are used to illustrate these methods. PMID- 3091110 TI - Solution conformations of B. subtilis ribosomal 5S RNA: a calorimetric study. PMID- 3091111 TI - Enzymatic HCO3- fixation: a common mechanism for all enzymes involved? PMID- 3091112 TI - Direct evidence for opposite effects of D-glucose and D-glyceraldehyde on cytoplasmic pH of mouse pancreatic beta-cells. AB - The effects of D-glucose, D-glyceraldehyde, glibenclamide, D-600, NH4+ and high concentrations of K+ on cytoplasmic pH (pHi) were investigated in dispersed and cultured pancreatic beta-cells from ob/ob mice. The cytoplasmic pH was measured with the fluorescent H+-indicator quene 1. The average pHi value in resting beta cells was 6.71. Addition of 20 mM of the physiological stimulus D-glucose increased pHi with 0.05 units. Both glibenclamide and high concentrations of K+ decreased pHi. The latter effects were completely reversed by D-600, supporting the notion that free cytoplasmic Ca2+ can be involved in the regulation of pHi. In contrast to D-glucose, 10 mM of D-glyceraldehyde decreased pHi by 0.09 units, an effect persisting even in the presence of D-600. From the present study it is evident that D-glyceraldehyde and D-glucose have opposite effects on pHi in pancreatic beta-cells. PMID- 3091114 TI - Light chains of immunoglobulins: structural-genetic correlates. PMID- 3091113 TI - [Effect of 17 alpha-ethinylestradiol on the activity of enzymes synthesizing and hydrolyzing cholesterol esters in the rat liver]. AB - Intraperitoneal injection of 25 micrograms/100 g body weight of 17 alpha-ethinyl estradiol to rats was shown to decrease serum cholesterol and to increase hepatic cholesterol. The rise in the level of non-labeled and C14-labeled free and esterified cholesterol in hepatic homogenate, as well as in lysosomal and cytosol fractions was accompanied by reduced activity of acyl-CoA-cholesterol acyltransferase and increased activity of lysosomal cholesterol esterase, as compared with the controls. The activity of cytoplasmic cholesterol esterase remained practically unchanged. Fistula bile of treated rats collected during 30 min was analyzed for the concentration of free cholesterol and bile acids. It has been shown that treatment of rats with 17 alpha-ethinyl estradiol caused an increase in hepatic cholesterol elimination via bile pathways. PMID- 3091115 TI - Biological and immunological characterization of ATG and ALG. AB - Antithymocyte globulin (ATG) and antilymphocyte globulin (ALG) are effective therapies in aplastic anemia; their mechanism of action is undefined. We assayed multiple properties of ATG and ALG to address the biological and immunological bases for differences between ATG and ALG and lot variation. In addition, we studied a lot reported to be inactive in an American clinical trial; however in retrospect, this lot appeared to be active in patients treated in Europe. Immunoprecipitation of thymocyte and lymphocyte membrane proteins with ATG and ALG showed between 14 and 18 major bands on SDS-PAGE, but the patterns for ATG and ALG were not identical. The ability of ATG and ALG to block binding of labeled monoclonal antibodies was assessed using flow cytometry and a radioimmunoassay. In general, there was more lot variation among ALGs than ATGs; however, all ALG lots were more potent blockers of binding of anti-HLA-DR and anti-Leu 1 antibodies than was ATG. Both ALG and ATG effectively blocked binding of anti-Leu 2a, anti-Leu 3a, anti-Leu 4, anti-Leu 5b, and anti-IL 2 receptor abs; neither blocked binding of anti-Leu 7. All preparations were capable of inducing T-cell blastogenesis, although there was considerable lot variation. All lots lysed 60% to 75% T cells in a rabbit complement-mediated cytotoxicity assay, with most having a plateau of activity at 5 to 10 ug/mL. Two lots of ALG, including the lot reported to be clinically inactive, showed less toxicity at suboptimal concentrations and did not plateau even at 80 ug/mL. In total, these results indicate important differences between ATG and ALG in general, more lot variation among ALGs than ATGs and only differences in cytotoxicity between an "inactive" lot of ALG and most, but not all, other active ATG and ALG preparations. PMID- 3091116 TI - Interleukin 3 promotes maturation of murine megakaryocytes in vitro. AB - A fluorescence assay for the quantitation of acetylcholinesterase (AchE) has been adapted for measurement of megakaryocytic maturation in short-term serum-free cultures of murine marrow. When marrow cells were cultured for 3 days in the presence of pokeweed mitogen-stimulated spleen cell conditioned medium (PWM-SCM) under serum-free conditions, AchE production was found to be related to the concentration of PWM-SCM. Interleukin 3 (IL3), a purified glycoprotein promoting the proliferation of several early hematopoietic progenitors including megakaryocytic colony-forming cells, also induced AchE production in a dose responsive manner. The response to IL3 was linearly related to the number of cells cultured. When marrow was first subjected to plastic adherence and the nonadherent cells then separated on Percoll gradients, a small megakaryocyte enriched population markedly depleted of colony-forming cells and large megakaryocytes, responded to IL3 in a similar dose-responsive manner. A significant amount of AchE was produced in the absence of any added factors. The data show that AchE production can be measured in 3-day serum-free cultures, and suggest that IL3, a factor promoting megakaryocytic proliferation in vitro, also promotes maturation. PMID- 3091118 TI - Limitations in the use of nickel boride dechlorination for the analysis of polychlorinated biphenyls. PMID- 3091117 TI - Metabolic enzyme induction in the rat by organic river sediment pollutants. PMID- 3091119 TI - Simplified determination of carbaryl in rainbow trout liver tissue. PMID- 3091120 TI - Surface and indoor air levels of polychlorinated biphenyls in public buildings. PMID- 3091121 TI - The costs of using gun control to reduce homicide. PMID- 3091122 TI - All-payer financing of uncompensated care: the New Jersey experience. PMID- 3091123 TI - The New Jersey DRG system and uncompensated care: some empirical results. PMID- 3091124 TI - Slouching toward national health insurance: the unanticipated politics of DRGs. PMID- 3091125 TI - Can DRG systems substitute for national health insurance? Paying for uncompensated care under all-payer DRGs. PMID- 3091126 TI - Roundtable discussion: some experience with the uncompensated care provisions of the New Jersey DRG system. PMID- 3091128 TI - Hospital cost containment and medical education. PMID- 3091127 TI - The issue is access: a personal reminiscence on the ethics and equity in New Jersey's DRGs. PMID- 3091129 TI - Tissue plasminogen activator. PMID- 3091130 TI - Management of raised intracranial pressure after severe head injury. AB - The mainstay of early management following severe head injury (less than 8 on the Glasgow coma scale [GCS]) remains urgent cardiopulmonary resuscitation, triage, transfer to a neurosurgical centre, emergency CT scanning and appropriate surgical intervention (Rose et al, 1977; Seelig et al, 1981; Langfitt and Gennarelli, 1982; Bricolo and Pasut, 1984). Subsequent therapy usually includes a period of intensive care with or without artificial ventilation (Becker et al, 1977; Bruce et al, 1978; Marshall et al, 1979). Intracranial pressure (ICP) monitoring is employed in many centres during the first post-traumatic week, however conservative or aggressive the management regimen is. PMID- 3091133 TI - Total parenteral nutrition: a four-year audit. AB - A four-year audit was carried out on 278 patients who received 289 courses of total parenteral nutrition (TPN) over 5213 patient days in a Saudi Arabian hospital. One hundred and forty-seven patients were discharged healthy, two of these after home TPN. The overall mortality was 36 per cent. ICU patients had the highest mortality (53 per cent). Among the survivors, 74.8 per cent showed an improvement in nutritional status. The incidences of metabolic complications and catheter sepsis were 2.9 per cent and 3.6 per cent, respectively. As a direct result of the audit, changes have been made in protocols and staffing patterns, and an attempt is being made to address the major problem of better selection of patients. PMID- 3091131 TI - Coronary vasoconstriction in the rat, isolated perfused heart induced by platelet activating factor is mediated by leukotriene C4. AB - Platelet-activating factor (Paf, 0.04-4.50 nmol) dose-dependently induced coronary vasoconstriction and decreased cardiac contractility in rat, isolated perfused hearts and concomitantly released leukotriene-like bioactivity into the cardiac effluent. Platelet-activating factor (0.9 nmol) induced an increase in 6 keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), PGF2 alpha, PGE2 and thromboxane B2 (TXB2) measured by radioimmunoassay (RIA) of cardiac effluents following partial purification using C18 Sep-Paks. The leukotriene-like bioactivity released by Paf was identified as leukotriene C4 (LTC4) using a combination of isolation on reverse phase-h.p.l.c. (r.p.h.p.l.c.) and quantitation by RIA. In addition, LTB4 was also identified by r.p.h.p.l.c. and the levels, determined by RIA, were within the range having biological activity. The release of cyclo oxygenase products by Paf was prevented by indomethacin (2.8 microM), markedly attenuated by diethylcarbamazine (7.7 mM) but unaffected by FPL 55712 (1.9 microM)-pretreatment. Furthermore, LTC4 (50 pmol) did not increase the release of the cyclo-oxygenase products measured. The release of LTB4 and LTC4 appeared to be unaffected by indomethacin pretreatment whereas diethylcarbamazine pretreatment markedly inhibited release. The coronary vasoconstriction induced by Paf (0.9 nmol) was attenuated by pretreatment with indomethacin or diethylcarbamazine, whereas FPL 55712 caused a marked inhibition of the response. In contrast, the decrease in cardiac contractility was prevented by indomethacin or diethylcarbamazine and unaffected by FPL 55712 pretreatment. It is concluded that LTC4 may be largely responsible for the coronary vasoconstriction induced by Paf with cyclo-oxygenase products having a possible modulatory role whereas the latter appear to be involved in the Paf-induced decrease in cardiac contractility. PMID- 3091134 TI - Obstetric anaesthetic services. PMID- 3091132 TI - The effects of monoamine oxidase inhibitors on the ejaculatory response induced by 5-methoxy-N,N-dimethyltryptamine in the rat. AB - The ejaculatory response and other components of the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-1, i.p.) were studied following single and repeated treatment of rats with eight different monoamine oxidase (MAO) inhibitors. Single and repeated treatment with the 5-HT agonist 5-MeODMT, and with low doses of the potent releaser of 5 HT, p-chloroamphetamine (PCA) were also included in the study. Repeated but not single treatment with 5-MeODMT reduced strongly but reversibly the ejaculatory response and the behavioural responses. Repeated but not single treatment with the nonselective and irreversible MAO inhibitors nialamide and pargyline reduced markedly the ejaculatory response but only slightly the 5-HT behavioural responses. Repeated treatment with the irreversible MAO-B inhibitor (-)-deprenyl, with the irreversible MAO-A inhibitor, clorgyline, with the reversible MAO-A inhibitor moclobemide, and with low doses of PCA did not affect either of the responses. Repeated but not single combined treatment with clorgyline plus PCA caused an almost complete blockade of all the four responses. The selective and reversible MAO-A inhibitors (as well as 5-HT releasers) amiflamine, alpha ethyltryptamine, and alpha-methyltryptamine reduced markedly the ejaculatory response after both single and repeated treatments. The behavioural responses were blocked only after repeated treatment. It is concluded that single and repeated treatments of rats with different MAO inhibitors do not produce a common alteration in 5-HT2 receptor functions. Repeated treatment with 5-MeODMT caused a blockade of 75-95% of the ejaculatory response and 5-HT behavioural responses. A similar strong blockade was only produced by the combined effect of MAO-A inhibition and 5-HT release. PMID- 3091135 TI - Can we eradicate hepatitis B? PMID- 3091136 TI - Dangers of snuff, both "wet" and "dry". PMID- 3091137 TI - Management of infection in the neutropenic patient. PMID- 3091138 TI - Orchidectomy versus oestrogen for prostatic cancer: cardiovascular effects. AB - One hundred consecutive patients aged up to 75 with newly diagnosed cancer of the prostate suitable for hormonal treatment were included in a controlled study of the cardiovascular effects of oestrogen versus orchidectomy. In all cases pre existing cardiovascular morbidity was excluded. Of the 100 patients, 91 were strictly randomised to receive either oestrogen (n = 47) or orchidectomy (n = 44) and 9 (6 given oestrogen, 3 orchidectomy) either chose their own treatment (five cases) or had it selected for them by the urologist (four). Oestrogen was given in the lowest recommended dosage in Sweden--namely, as 160 mg polyestradiol phosphate intramuscularly every month for the first three months, then 80 mg monthly, plus ethinyloestradiol 1 mg by mouth daily for the first two weeks, then 150 micrograms daily. At entry to the study the two treatment groups showed no difference in demographic characteristics or conventional risk factors for cardiovascular disease. During the first year, however, 13 (25%) of the patients given oestrogen suffered major cardiovascular events as compared with none of the patients after orchidectomy. Patients in the oestrogen treatment group who did not have minor signs of atherosclerosis at entry to the study suffered a similar incidence of cardiovascular complications to those who did have these signs at entry. The substantially increased risk of cardiovascular complications in patients given oestrogen for prostatic cancer warrants careful consideration when choosing treatment for this disorder. PMID- 3091139 TI - Risk of hypothermia in elderly patients with diabetes. AB - The incidence of admissions of patients with hypothermia was determined to examine whether hypothermia was more common in elderly patients with diabetes than in the general population after diabetic metabolic emergency cases had been excluded. A prospective survey of three accident and emergency departments identified 134 cases of hypothermia admitted from a catchment population of almost 157,000 aged 65 or over during the winters of 1981-2 to 1983-4. The predicted number of patients with diabetes in the population was nearly 5600 (3.5%). Twenty three admissions for hypothermia (17%) occurred in 20 patients with previously diagnosed diabetes. Women made up 87% of the diabetic admissions; the ratio of diabetic to non-diabetic admission rates in women was 7.9 (95% confidence interval 5.3 to 12.0). After excluding diabetic metabolic emergency admissions the ratio was 6.4. The ratio in men was 2.4, but the small number of admissions produced wide confidence intervals. Ten of the admissions with diabetes (43%) had pathological disorders that are associated with an increased risk of hypothermia. The frequency of these conditions is higher in patients with diabetes than in the general population and partly explains the increased risk of hypothermia in these patients. PMID- 3091140 TI - Effects of living with and looking after survivors of a stroke. AB - Information from a two year, longitudinal study on a community sample of patients with acute stroke was analysed to determine the effects of the stroke on the mood of the chief carer (the person living with the patient). Increased anxiety was the most commonly reported change six months after stroke. Significant depression was seen in 11-13% of carers over the first two years after stroke. The patient's functional disability was associated with depression in the carer over the first year but not at two years. A perceived poor recovery by the patient, a low level of general activities by the patient, and depression in the patient were also associated with depression in the carer within the first year. At two years after stroke none of the measured factors were related to a carer's level of depression. Carers of patients who have suffered stroke showed anxiety and emotional distress unrelated to the patient's physical disability after two years. More help from stroke support groups for carers is perhaps needed. PMID- 3091141 TI - Prevalence of known diabetes in an urban Indian environment: the Darya Ganj diabetes survey. PMID- 3091142 TI - Acute encephalopathy associated with campylobacter enteritis. PMID- 3091143 TI - Muscle damage induced by isotretinoin. PMID- 3091144 TI - Fish consumption and mortality from coronary heart disease. PMID- 3091145 TI - Findings of a national survey of the role of general practitioners in the treatment of opiate misuse: extent of contact with opiate misusers. AB - With the recent unprecedented growth in the spread of drug misuse in the United Kingdom the role of the general practitioner has become more and more prominent, both in response to demands for treatment and as the focus of national policy on drug misuse. Although general practitioners may be the first contact, few data are available on the extent of their contact with drug misusers. A postal survey was carried out in mid-1985 of a 5% national sample of general practitioners in England and Wales concerning their role in and views on the treatment of opiate misusers, including the extent of their contact with such patients during a four week period. Of the 1166 general practitioners surveyed, 845 replied, a response rate of 72%. The results show that roughly one in five general practitioners in England and Wales attended an opiate misuser during this four week period, seeing an estimated 6000 to 9000 patients, one third of whom were "new" to the general practitioner. A cautious estimate of between 30,000 and 44,000 new cases of opiate misuse presenting to general practitioners in a year is suggested, with some adjustment necessary because of double counting. A wide variation in the prevalence of consultations among regional health authorities was found, and several of the regions with a high prevalence are outside the London area. The scale of contact thus confirms the importance of the general practitioner in the national response to drug misuse. PMID- 3091146 TI - Obstetric anaesthetic services in the Yorkshire region. AB - A survey of obstetric anaesthetic services in the Yorkshire region, where about 44,500 deliveries take place annually, showed that inadequacies exist in the service to patients. A 24 hour epidural service is available in only nine of 19 consultant units, and in about seven units patients may have to wait up to half an hour for an anaesthetist to be available for an obstetric emergency. Additional consultant anaesthetic sessions are urgently required as well as centralisation of some units. PMID- 3091147 TI - Treatment of high blood pressure: should clinical practice be based on results of clinical trials? PMID- 3091148 TI - Complications resulting from misdiagnosing pseudogout as sepsis. PMID- 3091149 TI - Graduated elastic stockings. PMID- 3091150 TI - Manpower. PMID- 3091151 TI - Ingestion of button batteries. PMID- 3091152 TI - Technetium-99m autologous phagocyte scanning: a new imaging technique for inflammatory bowel disease. PMID- 3091153 TI - Treatment of the premenstrual syndrome by subcutaneous oestradiol implants and cyclical oral norethisterone. PMID- 3091154 TI - Length of survival of patients with AIDS. PMID- 3091155 TI - The real cost of joint replacement. PMID- 3091156 TI - Withdrawal of nomifensine. PMID- 3091157 TI - Systemic steroids in chronic severe asthma. PMID- 3091158 TI - Comprehensive bibliography database using a microcomputer. PMID- 3091159 TI - When things go wrong. PMID- 3091160 TI - Neurological manifestations of human immunodeficiency virus infection. PMID- 3091161 TI - Meniere's syndrome: pathogenesis and treatment. PMID- 3091162 TI - Immunity and depression. PMID- 3091163 TI - Dietary supplementation in pregnancy. PMID- 3091164 TI - Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy. AB - The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria. In an initial one week randomised single blind trial of captopril versus placebo, captopril (for nine patients) reduced arterial blood pressure from 148/94 (SD11/6) to 135/88 (8/7) mm Hg (p less than 0.05) and albuminuria from 1549 (range 352-2238) to 1170 (297-2198) micrograms/min (p less than 0.05), while glomerular filtration rate remained stable. No significant changes occurred in seven patients treated with placebo. During the 12 weeks of captopril treatment arterial blood pressure in all patients fell from 147/94 (11/6) to 135/86 (13/7) mm Hg (p less than 0.01), albuminuria fell from 1589 (range 168-2588) to 1075 (35-2647) micrograms/min (p less than 0.01), and glomerular filtration rate fell from 99 (SD19) to 93 (25) ml/min/1.73 m2 (p less than 0.01). The renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased concentrations of angiotensin I and renin. The study showed that glomerular filtration rate is not dependent on angiotensin II, that captopril reduces albuminuria, probably by lowering glomerular hypertension, and that captopril represents a valuable new drug for treating hypertension in diabetics dependent on insulin with nephropathy. PMID- 3091165 TI - Identifying men at high risk of heart attacks: strategy for use in general practice. AB - A strategy was devised for identifying men at high risk of acute myocardial infarction or sudden ischaemic death. A risk score was devised using cigarette smoking, mean blood pressure, recall of ischaemic heart disease or diabetes mellitus diagnosed by a doctor, history of parental death from "heart trouble," and the presence of angina reported on a questionnaire. The top fifth of the score distribution identified 53% of ischaemic heart disease cases--that is, men who subsequently experienced major ischaemic heart disease over the next five years. The addition of serum total cholesterol concentration and electrocardiographic evidence only slightly improved prediction (to 59%) and would have considerably increased the cost and effort of screening. Using this risk score on an opportunistic basis could be particularly valuable in general practice. Management of this high risk group is regarded as appropriate medical care and is complementary to the population approach to preventing ischaemic heart disease. Such a strategy for reducing the incidence of and mortality from ischaemic heart disease in men at high risk would also increase professional and public awareness of the need for preventive action. PMID- 3091167 TI - Public awareness of testicular cancer and the value of self examination. PMID- 3091166 TI - Effect of chorionic villus sampling and early pregnancy counselling on uptake of prenatal diagnosis. AB - An early pregnancy counselling clinic was introduced to improve the uptake of prenatal diagnosis and to offer chorionic villus sampling to women aged 38 and over by their expected date of delivery. Ninety eight (62%) unselected older mothers were seen before 11 weeks' gestation, and 23 (32%) of those with viable pregnancies elected to undergo chorionic villus sampling compared with 38 (52%) electing amniocentesis. A quarter of the patients booking before 11 weeks had a miscarriage. Because of the future potential demand for chorionic villus sampling counselling during pregnancy and referral of eligible patients should occur as early as possible. PMID- 3091168 TI - Smoking and colonic mucus in ulcerative colitis. PMID- 3091169 TI - Treatment of functional abdominal pain by transcutaneous electrical nerve stimulation. PMID- 3091170 TI - Leucocytoclastic vasculitis and pneumonitis induced by metformin. PMID- 3091171 TI - Chylopericardium, chylothorax, and hypobetalipoproteinaemia. PMID- 3091172 TI - Epidemics of fractures during periods of snow and ice. PMID- 3091173 TI - Fellowships in general practice in the St Thomas's district. PMID- 3091174 TI - Findings of a national survey of the role of general practitioners in the treatment of opiate misuse: dealing with the opiate misuser. AB - Because there has been a substantial increase in the scale of drug misuse general practitioners have become increasingly concerned in responding to this problem. Little is known, however, about how general practitioners manage drug misusers. The findings from a national survey carried out in mid-1985 of a 5% random sample of general practitioners in England and Wales show the extent to which various actions were undertaken by general practitioners who reported on the consultation with the opiate misuser whom they last attended. In more than half of the cases the opiate misuser had been under the care of the general practitioners for this problem for at least six months. The findings indicate that most general practitioners refer these patients to specialist drug dependence clinics or to general psychiatric services but rarely to other agencies. Opiate drugs had been prescribed in nearly a third of cases. The rate of notification to the Home Office conforms with that in other studies and indicates a high degree of undernotification. More detailed study of general practitioners' activities in managing drug misusers is needed. PMID- 3091175 TI - Factors influencing the routine recording of blood pressure. PMID- 3091176 TI - The acquired immune deficiency syndrome and epidemic of infection with human immunodeficiency virus: costs of care and prevention in an inner London district. AB - The epidemic of the acquired immune deficiency syndrome (AIDS) and infection with human immunodeficiency virus (HIV) necessitates early planning of services and allocation of resources. The use of hospital resources by patients with AIDS and the planned additional costs of clinical and preventive services for the epidemic of infection with HIV were calculated for an inner London health district that has treated 18% of the cases in the United Kingdom. Patients with AIDS required on average 50 days of inpatient hospital care each at an estimated current average lifetime cost of pounds 6800. These costs, however, underestimated the additional capital and revenue costs of planned new preventive and treatment services, estimated as being pounds 388,000 revenue and pounds 472,000 capital for 1986-7. It is important to invest now in preventive services throughout the United Kingdom to reduce the future social and financial costs of AIDS. PMID- 3091178 TI - Survival after treatment of carcinoma of the rectum. PMID- 3091177 TI - Is there an ideal body weight? PMID- 3091179 TI - Is inexperience a defence against negligence? PMID- 3091180 TI - Whatever happened to the Black report? PMID- 3091181 TI - Angina pectoris-like pains provoked by intravenous adenosine. PMID- 3091182 TI - Opiate withdrawal: inpatient versus outpatient programmes. PMID- 3091183 TI - Prevalence of multiple sclerosis in a south London borough. PMID- 3091185 TI - Diuretic treatment in decompensated cirrhosis and congestive heart failure: effect of posture. PMID- 3091184 TI - Implications of a district scheme to provide plastic insulin syringes to diabetics. PMID- 3091186 TI - Salt and the glycaemic response. PMID- 3091187 TI - Psoriasis. PMID- 3091188 TI - 5-Hydroxytryptamine-2 antagonist increases human slow wave sleep. AB - Ritanserin, a specific 5-HT2 antagonist, was given to volunteers in a double blind placebo controlled sleep study. Slow wave sleep doubled in duration at the expense of stage 2. The finding that a serotonin antagonist changed the architecture of sleep without producing insomnia is of fundamental importance and calls for a re-examination of traditional theories of sleep control which assign a facilitatory role to serotonin. PMID- 3091189 TI - Effects of electrical stimulation of the pontine A5 cell group on blood pressure and heart rate in the rabbit. AB - The effects of electrical stimulation of the A5 noradrenergic cell group of the ventrolateral pons was assessed in rabbits. Stimulation administered through either concentric bipolar or monopolar electrodes produced current-intensity related increases in mean arterial pressure (MAP). Decreases in heart rate (HR) accompanied the increases in MAP, but were essentially eliminated by bilateral vagotomy or destruction of the nucleus and tractus solitarii (NTS), thereby indicating that the HR decelerations were secondary to activation of baroreceptor reflexes. Neither vagotomy nor midcollicular section of the brainstem altered the MAP response to A5 stimulation. Bilateral destruction of the NTS slightly enhanced the response. Several rabbits received microinjections of 6 hydroxydopamine (6-OHDA) into the A5 region 2 weeks before the experiment. Other rabbits received vehicle injections and served as control subjects for the non specific effects of the 6-OHDA injections. 6-OHDA injections, but not vehicle injections, prevented the vasopressor effects of A5 stimulation. However, stimulation of the A1 noradrenergic nucleus of the ventrolateral medulla produced decreases in MAP in rabbits given prior microinjections of 6-OHDA into A5. These observations are interpreted to indicate that the 6-OHDA injections produced neurotoxic effects which were relatively restricted to the A5 region. Furthermore, the data from all of these experiments are interpreted as indicating that the vasopressor effects observed as a consequence of electrical stimulation of A5 are due to excitation of the noradrenaline-containing neuron cell bodies of this region and that this effect is mediated via pathways arising from this region and terminating in the intermediolateral cell column of the spinal cord. PMID- 3091190 TI - Striatal dopamine uptake and swim performance of the aged rat. AB - The striatum and olfactory tubercle of 30-month-old F344 rats contain significantly (21-24%) less dopamine compared with young adult (8-month) animals. However, rats of the two age groups show identical Km and Vmax values for the kinetics of [3H]dopamine uptake into striatal homogenates; uptake into the olfactory tubercle also appeared unaffected in old age. The preservation of dopamine uptake despite reductions in content of the transmitter suggests that the forebrain dopaminergic nerve terminals are intact, but that reduced dopamine synthesis and/or enhanced degradation may occur in the existing terminals. Administration to senescent animals of the dopamine uptake blockers nomifensine or bupropion (but not the norepinephrine uptake blocker desmethylimipramine) improved their swim performance to levels comparable with young adult animals. The findings suggest that amine reuptake may limit the synaptic effectiveness of dopamine released in the aged striatum. PMID- 3091191 TI - Magnetic field inhibition of morphine-induced analgesia and behavioral activity in mice: evidence for involvement of calcium ions. AB - An exposure for 60 min to a 0.5 Hz rotating magnetic field (1.5-90 G) significantly reduced the day-time analgesic (in CF-1 mice) and locomotory (in C 57BL mice) effects of morphine (10 mg/kg). Intracerebroventricular (i.c.v.) injections of a calcium chelator, EGTA, blocked these effects, while administration of the calcium ionophore, A23187, potentiated the inhibitory actions. In a parallel fashion, i.c.v. administration of Ca2+ reduced, in a dose related manner, the analgesic and locomotory effects of morphine in control CF-1 and C57 mice. These latter inhibitory effects could also be blocked by EGTA and augmented by A23187, indicating that opiate effects on activity and nociception are both sensitive to antagonism by calcium. Taken together these results suggest that exposure to magnetic stimuli may alter morphine-induced responses in mice, in a manner compatible and consistent with effects on Ca2+ and possibly other divalent ions. PMID- 3091192 TI - A newly discovered protein kinase C activator (oleic acid) enhances long-term potentiation in the intact hippocampus. AB - Protein kinase C can be activated by oleate, an unsaturated fatty acid. Since protein kinase C is activated by long-term potentiation, we wished to determine whether iontophoretic ejection of oleate into the intact hippocampal dentate gyrus of urethane-anesthetized rats would cause an enhancement of the response potentiated by high frequency stimulation of the perforant path. Oleate ejection did significantly enhance the persistence of the potentiated response. Moreover, a growth of the response beyond the initial potentiation was seen. Arachidonate, which stimulates protein kinase C to a lesser degree, had a significant preservation effect, but no effect on growth of the response. After vehicle and elaidate (trans-stereoisomer of oleate) ejections, the potentiated response decayed to baseline values. In addition, the persistence of the potentiated response observed two hours after its induction was positively correlated with the ability of an unsaturated fatty acid to activate protein kinase C in vitro. The present results support the proposal that protein kinase C activation enhances synaptic strength. It is suggested that one mechanism for this activation may be PLA2-mediated release of oleate. PMID- 3091193 TI - The effect of unilateral decortication on the patterns of pulsatile follicle stimulating hormone (FSH) and luteinizing hormone (LH) release and on mean plasma prolactin (Prl) levels in the ovariectomized rat. AB - Previous experiments have shown that unilateral decortication is followed by an elevation in FSH and LH secretion, but there has been no study of the rhythms of release of gonadotropins in these animals. Consequently, this study was undertaken to determine if there are alterations in the pulsations of gonadotropins following hemi-decortication and also to measure plasma Prl in these animals to determine if it might also be under the influence of extrahypothalamic pathways. Our results show an increased mean plasma LH in unilateral decorticate animals that occurred because of an increase in pulse frequency without a significant increase in pulse amplitude. Mean plasma FSH was also elevated significantly in unilaterally decorticate animals, but there was no significant change in pulse frequency or amplitude. The length of the interpulse interval for LH release secretion decreased in unilateral decorticate animals, whereas the length of the cycle of FSH secretion increased in this circumstance. The mean levels of Prl were reduced in unilateral decorticate animals. These changes indicate that unilateral removal of cortico-rhinencephalic structures has an excitatory influence on gonadotropin secretion mediated by an increased frequency of LH and decreased frequency of FSH pulsations in the castrate, while at the same time there is a lowering of plasma Prl, probably due to removal of excitatory cortico-rhinencephalic pathways. PMID- 3091194 TI - Dose related effects of 6-OHDA on rabbit retinal dopamine concentrations and ERG B-wave amplitudes. AB - The purpose of this study was to examine the dose related effects of 6 hydroxydopamine (6-OHDA) on the electroretinographic (ERG) B-wave amplitude and on retinal concentrations of dopamine (DA) and its main metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). Doses of 6-OHDA (60, 300 or 1200 micrograms) were dissolved in a 0.9 percent NaCl and ascorbic acid solution and administered intravitreally in 300 microliter volume in one eye of adult pigmented rabbits. The fellow eye received a similar volume of the drug vehicle. With the smallest dose of 6-OHDA (60 micrograms) no changes in ERG B-wave amplitude or retinal concentrations of DA, DOPAC or HVA were found. With the largest dose of 6-OHDA (1200 micrograms) complete extinction of the ERG and almost total disappearance of DA, DOPAC and HVA were observed. With the intermediate dose of 300 micrograms 6-OHDA significant increases in B-wave amplitudes and decreases in retinal DA, DOPAC and HVA concentrations were obtained. This latter dose did not affect retinal concentrations of serotonin (5 HT), 5-hydroxyindole acetic acid (5-HIAA) and norepinephrine (NE). These results demonstrate that selective reductions of retinal dopamine and its metabolites can be obtained with a single intravitreal injection of 300 micrograms 6-OHDA in rabbits. The observed concomitant increase in B-wave amplitudes lends support to the hypothesis that DA acts as a mediator of lateral inhibition in the retina. PMID- 3091195 TI - [Granulocyte labeling using indium-111 oxinate. Application to the diagnosis of abscesses and the study of cryptogenic enterocolitis]. PMID- 3091196 TI - A cost/effectiveness evaluation of lay therapy treatment for child abusing and high risk parents. AB - This longitudinal investigation tested the effectiveness and cost-efficiency of a lay therapy treatment program in comparison with a standard social work treatment approach. A pretest-extended posttest research design was used to follow a group of child abusing and high risk mothers who received lay therapy (N = 27) and a randomized control group of similar clients (N = 28) over a 12-month period. Outcome data were obtained through interview and direct observation of the parents and children at six-month intervals. A variety of standardized instruments were used including Cattell's 16 Personality Factor Test, Coopersmith's Self-Opinion Form, and the Nurturance and Parent Observation Scales, adapted from Baumrind. Treatment success was defined as progression toward the mean scores of a matched comparison group (N = 21) obtained from the general population of the community during the pretest. The results indicated a trend toward improvement on the outcome measures for both treatment groups. The group receiving lay therapy treatment improved only slightly more than the group receiving standard treatment; however, there was also significantly less attrition with the lay therapy group. Analysis of time budget study data indicated that the lay therapists spent an average of 17.46 hours per month with each of their clients thus permitting the social workers to spend considerably less time with lay therapy clients. Analysis of the direct costs of the programs, based on time budget information, indicated that the lay therapy treatment involved more direct client contact than the standard treatment approach and was also substantially more costly. The high cost of the program was attributed to low caseloads and redundancy in supervision. This study presents several practical program and research recommendations. PMID- 3091198 TI - [Postprandial exchange of urea and ammonia nitrogen between the digestive tract and portal blood in the conscious pig after ingestion of a diet with or without urea]. AB - The concentrations of urea and ammonia were measured in the portal and arterial blood simultaneously to the blood flow rate in the portal vein during the postprandial period (8 hrs.) after ingestion of a normal protein diet with 3% urea (10 meals) or without urea (12 meals) in conscious pigs (mean body weight: 55.5 +/- 2.3 kg). When no urea was present in the diet, there was a slight and permanent uptake of blood urea by the gut (570 mg/h, i.e. 9,5 mmoles/h) as well as a permanent appearance of ammonia in the portal vein (258 mg/h i.e. 15.2 mmoles/h), increasing with time (P less than 0.05). The absorbed ammonia nitrogen represented a maximum of 70% of urea nitrogen taken up. 2. Addition of urea to the diet brought about a large absorption of that substance (73% of the ingested amount) followed by a rather large excretion (960 mg/h, i.e. 16 mmoles/h), 5-6 hrs. after the meal and led to an increase (P less than 0.05) in the absorption of ammonia. PMID- 3091197 TI - [Effects of DTT and thioredoxins on rat argininosuccinate synthetase activity in vitro]. AB - Argininosuccinate synthetase (ASS, EC 6.3.4.5), the third enzyme of urea-cycle, was studied in desactivated extracts of rat liver. The enzyme is activated, in vitro, by Mg2+ ions (5 mM) and dithiothreitol (DTT: 10 mM). After reduction by DTT, thioredoxins isolated from rat liver were able to activate ASS by 370%. PMID- 3091200 TI - [Abnormal localization of proto-oncogene c-ets 1 in acute leukemia with translocation t(1: 11)(q21: q23)]. AB - The chromosome localization of a 5.4 kb DNA genomic probe of proto-oncogene c-ets 1 has been analysed in an acute monocytic leukemia with t (1; 11) (q21; q23) translocation. The c-ets probe has been translocated onto the rearranged chromosome 1, suggesting the involvement of the proto-oncogene in leukemias with chromosome rearrangements at band 11 q23. PMID- 3091199 TI - [Demonstration and localization of synapsin I in vestibular receptors in the cat: immunocytochemical study]. AB - The presence and localization of synapsin I, a neuron-specific phosphoprotein, was investigated in the cat vestibular epithelium, using a rabbit antisynapsin I anti-serum. The staining was performed by immunofluorescence or by a peroxidase antiperoxidase (PAP) technique. A strong immunoreactivity was observed with both methods. This immunoreactivity appeared as spherical patches distributed in the lower part of the epithelium. This distribution pattern is very similar to that of the efferent synaptic endings which form axodendritic synapses with the afferent nerve chalice of type I hair cells, or axosomatic synapses with type II hair cells. Some of the nerve chalices were also labelled; in this case, the immunoreactivity was more evident with PAP staining. These results thus suggest the presence of large amounts of synapsin I in the vestibular efferent nerve endings. These endings are known to be filled with numerous synaptic vesicles. This localization of synapsin I is well correlated with previous work that report a close association between synapsin I and small synaptic vesicles. The presence of synapsin I in sensory endings such as the afferent nerve chalices was unexpected and is under investigation. PMID- 3091201 TI - [Effect of serum fractions on the incorporation of tritiated thymidine in activated lymphocytes: I. Human serum from normal adult subjects]. AB - Fractionation of normal human adult serum using Centrisart or gel filtration at neutral pH shows that serum thymidine activity, measured as the ability to stimulate the 3H-thymidine uptake into lectin-activated lymphocytes, is represented by several molecular forms distinct from the endogenous Sm-C. The main thymidine activity is found in the 50-70 K range. PMID- 3091202 TI - [Immunotoxicotherapy: protective effect of anti-colchicine antibodies in acute colchicine poisoning in rabbits and mice]. AB - Anti-colchicine antibodies are able to neutralize toxic effects of colchicine after acute intoxication in rabbits and mice. The protecting effect is demonstrated by active immunization (rabbits) or passive immunization (mice). These data suggest that the immunotoxicotherapy may be useful for compounds (colchicine) with intracellular action. PMID- 3091203 TI - [Induction of arthritis in mice by injection of homologous type II collagen]. AB - Immunization with heterologous type II collagen (CII) induces arthritis in DBA/1 mice, a strain genetically susceptible to this disease. In order to develop an experimental model of autoimmunity more adequate for the study of human Rheumatoid Arthritis, DBA/1 mice were injected with homologous native CII. About 6 weeks later, the animals developed a chronic progressive polyarthritis assessed by clinical observations and histologic examination. The incidence of arthritis as well as the severity of the disease are clearly higher in males. Conversely, the secretion of autoantibodies raised against mouse CII is correlated neither with sex nor with activity score of the arthritis. PMID- 3091204 TI - [Effect of serum fractions on the incorporation of tritiated thymidine in activated lymphocytes: II. Comparison between cord blood and the blood of newborn infants]. AB - After serum Sephacryl 300 gel filtration, the major circulating forms of TA in serum are macromolecular. However different patterns are found in cord blood and in the blood of newborns at 24 hr of life. The low values found in cord blood are not due to inhibiting factor(s). TA in serum fractions does not parallel immunoreactive Sm-C levels. The pattern of immunoreactive Sm-C are similar in both cord blood and newborn blood. PMID- 3091205 TI - [Isoflurane in spontaneous ventilation (in orthopedic surgery: comparison with halothane)]. AB - Isoflurane and halothane, two anaesthetics agents have been compared. Forty young and healthy patients were divided into two randomly selected group. Each of them was anaesthetized either with isoflurane or with halothane. Anaesthesia was maintained with nitrous-oxide and dextromoramide. During induction, the ventilation was spontaneous. Blood-gas, ventilation rate and tidal-volume were studied before induction, during anaesthesia and at the end of the surgery. Statistical data show a higher PaCO2 and a lower pH with isoflurane. This was increased by dextromoramide. During induction, complications occurred more after than with halothane but the emergence was better. PMID- 3091206 TI - [Natural blood and artificial blood in rapid vascular filling]. PMID- 3091207 TI - [Jejunostomy for feeding in geriatric digestive surgery]. PMID- 3091208 TI - [Establishment and biological characteristics of a cell line from osteosarcoma induced by 241Am in rats]. PMID- 3091209 TI - [Histomorphological study on the damage of canine coronary vessels caused by acute low-flow perfusion]. PMID- 3091210 TI - [Serum folic acid and vitamin B12 levels in normal adults in Beijing]. PMID- 3091211 TI - [Clinical use of transcutaneous bilirubinometry]. PMID- 3091212 TI - [Iodine metabolism and hypothalamic, pituitary and thyroid functions in residents in an endemic goiter area]. PMID- 3091214 TI - [Cardiothermographic study of the effects of tetrandrine on experimental myocardial ischemia and infarction]. PMID- 3091213 TI - [Analysis of 223 cases of hereditary deafness]. PMID- 3091215 TI - [Masked depression among patients diagnosed as neurosis in general hospitals]. PMID- 3091216 TI - [Long-term follow-up studies on patients poisoned by cottonseed oil]. PMID- 3091217 TI - [CT diagnosis of adrenalopathy: analysis of 81 cases]. PMID- 3091218 TI - [Radioimmunoassay of aldosterone in saliva and its preliminary clinical use]. PMID- 3091219 TI - Protozoal diseases. AB - The clinical and pathologic findings of and therapy for such protozoal diseases as equine protozoal myeloencephalitis, toxoplasmosis, sarcocystosis, pneumocytosis, cryptosporidiosis, giardiasis, besnoitiosis, and klossiellosis are discussed. Emphasis is placed on disorders that occur with greater frequency in North America and on emerging protozoal diseases affecting horses. PMID- 3091220 TI - The effect of bone cell stimulatory factors can be measured with thymidine incorporation only under specific conditions. AB - This study examines the efficacy of using radiolabeled thymidine as a measure of bone cell DNA synthesis. The effect of a bone-active peptide on cell proliferation is assessed under different labeling conditions and it is shown that the apparent stimulation in DNA synthesis is due to an increase in participating cells and not to labeling artifacts. In another series of experiments we demonstrate how the use of carrier-free thymidine can cause erroneous results. From these data it is shown that only 10-28% of the cells in culture are participating in DNA synthesis. Therefore, under specific conditions, a 100% stimulation in thymidine incorporation by a mitogenic factor can be caused by as little as a 10% increase in the number of DNA synthesizing cells. PMID- 3091222 TI - Nonmineralized and mineralized bone collagen in bone of immobilized monkeys. AB - Monkey bones from different time periods of immobilization and reambulation of the monkeys were assessed histologically. The bone was also assessed biochemically for nonmineralized collagen in bone. Results indicate that more nonmineralized bone is present in monkeys that have been immobilized, and upon reambulation, these values tend to be normalized to control bone. PMID- 3091221 TI - The changes in quality of mandibular bone mineral in otherwise totally immobilized rhesus monkeys. AB - The status of bone mineral and osteocalcin in the young adult Rhesus monkey mandible was assessed following a 14-day period of postcranial immobilization, and after 7- and 28-day recovery periods. Specimens of cortical bone taken from the compact bone at the inferior border of the jaws were ground in liquid nitrogen and sieved to a particular size below 20 micron. The bone powder was then fractionated in a bromoform-toluene density gradient to determine its mineralization profile (Ca, P, CO3, and osteocalcin), and X-ray diffraction was used to determine apatite crystal size in some fractions. There was no change in the chemistry of the mandibular bone from the immobilized animals. However, the mineralization profile in that group showed a significant shift toward the higher density fractions, indicating the presence of a greater than normal content of mature well-mineralized bone. While this trend was accentuated in the jaws following a 7-day postimmobilization recovery period, partial recovery of the normal profile was observed after a 28-day recovery period. The osteocalcin profile shifted like the mineralization profile during the immobilization and recovery periods. X-ray diffraction analyses showed that the shift in the mineralization profile during the immobilization period was associated with a decrease in apatite crystal size. PMID- 3091223 TI - Mechanical properties of collagen from decalcified rat femur in relation to age and in vitro maturation. AB - Cortical bone collagen was obtained by decalcifying femoral bones from 2-, 5-, 15 , and 25-month-old male rats. Collagen specimens were cut longitudinal to the long axis of the femur and tested mechanically. The maximum load (ultimate strength) and maximum slope of the load-strain curve (maximum stiffness) were found to decrease with age. The age-related reduction in the mechanical parameters resulted from a change in the mechanical strength of the constituent collagen and a change in the morphology of the bone tissue. In vitro aging, produced by incubating for 0-5 months, did not change the mechanical strength of bone collagen specimens obtained from 2-month-old rats. The changes in the mechanical characteristics of bone collagen, accompanying in vivo and in vitro aging are the opposite of those observed in soft tissue collagen. In the latter there is an increase in the mechanical strength during in vivo and in vitro aging. PMID- 3091224 TI - The effect of orchidectomy on bone metabolism in aging rats. AB - We have shown that orchidectomy in postpubertal 55-day-old rats led beyond 2 months to a decrease in bone growth and loss of weight. At 1 month postorchidectomy, we observed a three-fold increase in bone blood flow, an increase in calcium accretion rate, and an increase in the number of osteoclasts in the metaphysis. In the present experimental study, orchidectomy was performed in 1-year-old rats when bone growth in length was no longer measurable. In the tibia and femur we observed a decrease in bone volume, a still more rapid decrease of bone calcium during the first postoperative month, a thinning of the cortical width, an initial increase in calcium accretion rate (+20% when compared to 31 days controls) followed by a decrease at 120 days (-22% and -11% when compared to controls for tibia and femur respectively), a 29% increase in bone blood flow, and an increase in the number of osteoclasts. We conclude that androgen deprivation in young and old animals leads to a modified bone architecture, independent of the androgen impact on bone growth. PMID- 3091226 TI - Osteoclastic features of cells that resorb bone implants in rats. AB - The subcutaneous implantation of devitalized, mineral-containing bone particles in rats elicits the recruitment and differentiation of multinucleated cells and the rapid resorption of the bone. Cytochemical and ultrastructural characteristics were studied 12 days after implantation of bone. Tartrate resistant acid phosphatase activity was demonstrated in these cells, especially at the cell/bone interface. Mast cells were seen vicinal to, but not in contact with the osteoclasts and the bone particles. Electron microscopic evaluation revealed that many multinucleated cells in lacunae on the surfaces of the bone particles displayed features characteristic of in osso osteoclasts, including clear zones of attachment to the bone substrate, and ruffled borders overlying bone with frayed collagen fibers. Many cells contained multiple giant centrospheres; this finding suggests that fusion can occur between multinucleated cells. This model may be useful to characterize the differentiation and regulation of bone-resorbing cells. PMID- 3091227 TI - Cadmium transport by a Cd2+-sensitive and a Cd2+-resistant strain of Bacillus subtilis. AB - Cadmium uptake by a Cd2+-sensitive (1A1) and a Cd2+-resistant mutant (1A1r) strain of Bacillus subtilis was investigated. Uptake of 109Cd2+ was determined for cells of both strains grown in tryptone broth and in broth containing tryptone, yeast extract, and glucose (TYG). The extent of 109Cd2+ uptake by cells of 1A1r was less than by cells of 1A1 under both growth conditions. In both growth media, 109Cd2+ uptake by 1A1 cells demonstrated saturation kinetics and was energy dependent. In both TYG and tryptone broth, 109Cd2+ uptake by 1A1 cells was inhibited by the addition of unlabeled Mn2+. Although lower in magnitude, the kinetics of 109Cd2+ uptake by 1A1r cells were similar to those of 1A1 cells when grown in tryptone broth. However, no obvious saturation kinetics, energy dependence, temperature sensitivity, or inhibition of 109Cd2+ uptake by the addition of unlabeled Mn2+ was observed in 1A1r cells grown in TYG. Differential Mn2+ accumulation by 1A1r cells in TYG and tryptone broth correlated with differential 109Cd2+ uptake by 1A1r cells in these media. PMID- 3091225 TI - The differences in calcium distribution pattern between preodontoblasts and preameloblasts in developing rat molar tooth germs. AB - Ultrastructural localization of calcium in preodontoblasts and preameloblasts was investigated using the potassium pyroantimonate technique, and it was confirmed that there were clear differences in calcium distribution pattern between preodontoblasts and preameloblasts. In preodontoblasts, pyroantimonate reaction products were mainly observed in the Golgi region, lateral intercellular spaces, and secretory granules, especially in the distal portion of cell body; however, few were found in mitochondria and on the plasma membrane. In preameloblasts, on the other hand, the precipitates were located in mitochondria, nuclei, and on the inner face of the plasma membrane; however, few reaction products were observed in the intercellular spaces, lysosomelike granules, secretory granules, and stippled materials. Granular reaction product approximately 20-40 nm in diameter adhered preferentially to the growing end of needlelike crystals in the initial enamel matrix. PMID- 3091229 TI - Physicochemical roles of soluble metal cations in the outer membrane of Escherichia coli K-12. AB - Atomic absorption spectroscopy of isolated native and EDTA-modified (lipopolysaccharide-depleted) outer membrane revealed trace amounts of potassium, manganese, and iron (1.0-7.0 nmol/mg dry weight outer membrane). Sodium, magnesium, and calcium were approximately one order of magnitude more plentiful, but EDTA-modified outer membrane was deficient in calcium. When metal-binding assays were conducted to find the binding capacity of native and EDTA-modified outer membrane, potassium bound poorly compared with sodium. However, there was no difference in the binding of these ions between the OM preparations. In contrast, reduced amounts of magnesium, calcium, manganese, and iron III bound to the EDTA-modified OM. Partitioning of intact cells in a biphasic dextran polyethyleneglycol system indicated that the reduced lipopolysaccharide content of the EDTA-modified outer membrane increased the hydrophobicity of the cell surface. Exposure of control and EDTA-treated cells to divalent metal salt solutions before phase partitioning also increased cell surface hydrophobicity. Freeze-etching showed that sodium ions had no effect on the membrane fractures observed in control cells, but with EDTA-treated cells, this cation increased the occurrence of small outer membrane fractures (plateaus) which are characteristic of EDTA treatment. Both magnesium and manganese increased the frequency of outer membrane cleavage in control cells, whereas calcium did not. In contrast, all three divalent metallic ions increased the frequency and extent of cleavage in the outer membrane of EDTA-treated cells. PMID- 3091228 TI - Molybdenum nutrition of isolates of four Aspergillus species. AB - The molybdenum requirement for growth and conidial formation by Aspergillus flavus, A. terreus, and A. sulphureus was found to be 0.2 ppb, which was one fifth that of an A. niger isolate. Molybdenum deficiency depressed growth, conidial formation, dry weight, soluble protein, and the specific activities of nitrate reductase, succinic dehydrogenase, and aconitase in all the isolates of Aspergillus studied, but the specific activities of catalase and peroxidase were depressed only in isolates of A. niger, A. terreus, and A. flavus. Also, molybdenum deficiency stimulated the specific activities of acid phosphatase and ribonuclease in the A. flavus isolate, although the specific activities of these enzymes decreased in other isolates. Eighteen hours after the addition of molybdenum (5 ppb) to molybdenum-deficient (0.02 ppb) cultures of A. niger, the specific activities of catalase, peroxidase and succinic dehydrogenase were restored in the absence of cycloheximide, while the specific activity of nitrate reductase was recovered even in the presence of the inhibitor. There was no effect on the specific activities of aconitase and acid phosphatase following the addition of molybdenum to molybdenum-deficient cultures of A. niger. PMID- 3091230 TI - Structure, partial elemental composition, and size of Thiopedia rosea cells and platelets. AB - The phototrophic purple sulfur bacterium Thiopedia rosea forms multicellular, gas vacuolate, regular, flat aggregates (platelets, sheets) held together by slime. Platelets found in eutrophic water consisted of slime (85% of the total wet volume) and 16 cells, while the gas-filled vacuole occupied 44% of the volume of a single wet cell. Individual platelet cells contained central spindle-shaped gas vesicles (which together constitute the cell's gas vacuole), intracytoplasmic membrane vesicles (chromatophores), and peripheral sulfur globules. Cells were surrounded by a Gram-negative type cell envelope and were connected to neighboring cells of the same platelet by mostly unstructured slime. Cells contained detectable amounts of magnesium, phosphorus, sulfur, and potassium as determined by wavelength-dispersive X-ray microanalysis. The large size and relatively low slime density of the platelet, as well as the flat shape, could greatly decrease platelet sedimentation and so stabilize the position of T. rosea within its water column. PMID- 3091231 TI - Free and total serum valproate concentrations: their relationship to seizure control, liver enzymes and plasma ammonia in children. AB - The relationships between total and free serum valproate (VPA) concentrations and seizure control, serum liver enzyme activity and plasma ammonia concentration were studied in 61 epileptic children. Enzyme-immunoassay (EMIT)R methods gave higher values of total VPA concentration than gas-liquid chromatography (GLC) methods. In over 80% of children with complete seizure control the ranges of total VPA concentration were 140-420 mumol/L with GLC methods and 210-560 mumol/L with EMIT methods. The range of free VPA concentrations in 78% of children with complete seizure control was 8.8-26.4 mumol/L. Increased liver enzyme activity was observed in 6 of the 61 children and raised plasma ammonia concentration in 11 of 50 children. Plasma ammonia concentration was related to total serum VPA but was not related to free serum VPA. Increased serum liver enzyme activity was related to VPA dose per kg but not to free or total serum VPA concentration. Thus free VPA concentrations do not appear to be more useful than total VPA concentrations in predicting seizure control and do not correlate with liver enzyme activity or plasma ammonia concentration. PMID- 3091232 TI - Antibody responses in protein-energy restricted beef cows and their cold stressed progeny. AB - Antibody titers were measured in serum and colostral whey of pregnant beef cows immunized with tetanus toxoid and chicken red blood cells while being fed diets either restricted or nonrestricted in protein and/or metabolizable energy during the last 150 days of gestation. Serum antibody titers were also measured in the colostrum-fed, cold and noncold stressed progeny that were actively immunized with dinitrophenol conjugated to keyhole limpet hemocyanin. In general, there were no major or sustained differences in humoral immune responses to injection of tetanus toxoid or chicken red blood cells between cows fed diets that were adequate or restricted in protein or metabolizable energy. In the few cases where serum antibody titers to tetanus toxoid or chicken red blood cells differed (P less than 0.05) between adequately fed or restricted cows, the differences were no greater than twofold. Anti-chicken red blood cell titers were uniformly low (P less than 0.05) by a magnitude of two to threefold in colostral whey of cows restricted in protein and/or metabolizable energy when compared to titers in cows fed adequate amounts of protein and metabolizable energy. With one exception, neither maternal dietary restriction nor cold exposure had a major effect on the ability of the calves to absorb antitetanus toxoid and chicken red blood cell antibodies from colostrum. The humoral immune responses of all calves to injection of keyhole limpet hemocyanin and dinitrophenol were similar in magnitude. PMID- 3091234 TI - In-vitro susceptibility of 400 isolates of Neisseria gonorrhoeae in Vancouver, 1982-84. AB - Consecutive isolates of Neisseria gonorrhoeae obtained at a sexually transmitted disease clinic in Vancouver between June 1982 and June 1984 were tested for in vitro susceptibility to eight antimicrobial agents. Of the 400 isolates 6 (1.5%) were penicillinase-producing N. gonorrhoeae, and for 25 (6.2%) the minimum inhibitory concentrations (MICs) of penicillin were 1.0 to 4.0 micrograms/ml. Ceftriaxone sodium was the most active agent. The MICs were higher than those reported in a Canadian study in 1973-74, except for tetracycline hydrochloride. The patterns of susceptibility of the isolates to one antimicrobial agent correlated significantly with those to each other agent, although the relation was weakest for trimethoprim-sulfamethoxazole and spectinomycin. The results reinforce the need to evaluate local in-vitro susceptibility patterns, especially since the proportion of isolates with relative and absolute resistance to penicillin is increasing. PMID- 3091235 TI - US groups eyeing merits of Canadian-style national health program. PMID- 3091233 TI - Plasma concentration profiles of gonadotrophins and testosterone in the adult boar. AB - Follicle stimulating hormone, luteinizing hormone and testosterone were measured by radioimmunoassay in plasma samples collected at 15 min intervals for a 12 h period in eight adult boars. Pulse increases in follicle stimulating hormone concentrations varied from one to four between individual boars while those of luteinizing hormone ranged from zero to four. The index of hormone production, provided by calculation of the area under the curve, was 0.5 +/- 0.51 microgram/L (means +/- S.D.) for follicle stimulating hormone and 0.46 +/- 0.11 microgram/L (means +/- S.D.) for luteinizing hormone. A significant correlation between changes in follicle stimulating hormone and luteinizing hormone values was seen in only two boars. The mean plasma testosterone concentration was 7.43 +/- 1.58 nM/L (means +/- S.D.). An identified increase in testosterone values occurred once in the 12 h period for six of the boars but was not noted in the other two animals. Although increases in testosterone could be identified with a previous pulse of luteinizing hormone, not all luteinizing hormone pulses were followed by an elevation in testosterone. A significant correlation between luteinizing hormone and testosterone was present in three of the eight animals. Follicle stimulating hormone and luteinizing hormone were measured in samples similarly collected two weeks after castration in the same eight boars. The number of pulses of follicle stimulating hormone increased significantly (p less than 0.05) and ranged from 3 to 7/12 h. The index of production of 1.8 +/- 1.15 micrograms/L (mean +/- S.D.) also represented a significant increase (p less than 0.05) over precastration follicle stimulating hormone values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091236 TI - Resistant ovary syndrome and premature ovarian failure in young women with galactosaemia. AB - Three young women with galactosaemia presented with amenorrhoea and elevated plasma levels of FSH and LH. Two of these women are sisters and ovarian biopsy confirmed premature ovarian failure in one and resistant ovary syndrome in the other. The history and ovarian histology suggested that the sister with ovarian failure may have progressed through a stage of 'follicle resistance' prior to follicular atresia. All subjects had specific bioassays for LH which were grossly elevated, and higher than the levels recorded by immunoassay. PMID- 3091237 TI - An analysis of the LH profile in relation to ovarian stimulation regimes and embryo transfer rates in an in vitro fertilisation programme. AB - A total of 128 patients undergoing 250 in vitro fertilisation (IVF) treatment cycles were studied to determine the relationship between ovarian stimulation regime, the status of the oestradiol levels in the 2 days prior to human chorionic gonadotrophin (hCG) administration and/or the onset of the luteinizing hormone (LH) surge, and the outcome of treatment cycles. The results demonstrated that hCG administration significantly improved the embryo transfer (ET) and pregnancy rates, although the mean interval between cessation of human menopausal gonadotrophin (hMG), and the onset of the LH surge also influenced the ET rate. hMG in conjunction with clomiphene citrate did not suppress the endogenous LH surge but enhanced the oestradiol levels in the 2 days prior to hCG administration and/or the onset of the LH surge. In stimulated cycles the diurnal rhythm of urinary LH surges was abolished. Finally, in certain patients, the LH pattern appeared to be repeated in sequential treatment cycles. PMID- 3091238 TI - The physician and resource allocation. AB - Even though there is substantial pressure on physicians to significantly reduce the amount of public monies spent on geriatric health care, it is improper for physicians to let financial concerns take precedence over their obligations to care for the patients who seek their services and assistance. The doctor/patient relationship demands that the physician be faithful to the cause of meeting the needs of patients. This faith is kept by taking all necessary steps to respect and promote the autonomy of patients. This is best done by adhering to a commitment of pursuing a process of communication with patients that leads to the attainment of informed consent or refusal from patients. Two consequences likely to follow are protection of many patients from protracted, miserable deaths because of less use of invasive medical procedures, and subsequent financial savings from this lower degree of use. PMID- 3091239 TI - High technology in geriatric care. AB - The use of technology in the care of the elderly can be very important in maintaining the quality of the lives of individuals with functional impairments. Advanced technology is not inherently costly, and its use in selected situations may be of less cost than current practices. Intelligent and compassionate use of these technologies will require our best efforts to allow the aged to share in the benefits such scientific advantages can bring. PMID- 3091240 TI - Nursing home care. AB - The intent of this review is to highlight several difficult questions from a personal perspective while caring for debilitated elderly patients in a nursing home. These problems appear to be encountered less frequently in the acute-care setting. Where possible, supporting literature is cited and legal precedent is indicated. The following topics, among others, are discussed: a framework for physicians' ethical decisions, basic ethical principles, typical problems encountered by the physician, and considerations for withholding treatment. PMID- 3091241 TI - Intravesical chemotherapy. Studies on the relationship between pH and cytotoxicity. AB - The influence of pH on the antitumor activity of drugs used for intravesical chemotherapy was studied. A human continuous cell line derived from a transitional cell carcinoma of the bladder was exposed to 6 drugs (Adriamycin [doxorubicin], cisplatin, epirubicin, epodyl, mitomycin C, and thiotepa) for 1 hour at 11 pH values ranging from 5.2 to 9.7, and cytotoxicity was measured by inhibition of colony formation. pH had a marked influence on drug activity: cisplatin, mitomycin C, and thiotepa were most cytotoxic in acid media, Adriamycin, and epirubicin in alkaline media, while epodyl was the only drug whose cytotoxicity was unaffected by pH. In addition to these in vitro studies, comparisons were made of the pH of urine samples obtained from patients immediately before and at the completion of intravesical chemotherapy. Changes in pH up to a maximum of +/- 1.6 units were observed, although in most cases, values were similar before and after therapy. All the drugs used were acidic in solution, with the exception of thiotepa. It is concluded that by adjusting solvent and urine pH to the optimum value for each drug, the effectiveness of intravesical chemotherapy might be enhanced. PMID- 3091243 TI - Total parenteral nutrition and cancer clinical trials. AB - Twenty-eight prospective randomized controlled clinical trials evaluating the use of total parenteral nutrition (TPN) in cancer patients were identified through a search of major indexing sources. The data were pooled across studies to increase the ability to detect therapeutic effects. The impact of publication bias and the quality of reporting each trial were used to critically assess the conclusions drawn from the pooled analysis. The authors conclude that TPN may be useful when used preoperatively in patients with gastrointestinal tract cancer. It appears to be beneficial in reducing major surgical complications (pooled P = 0.01) and operative mortality (pooled P = 0.02). No statistically significant benefit from TPN could be demonstrated in survival, treatment tolerance, treatment toxicity, or tumor response in patients receiving chemotherapy or radiotherapy. An increase in the risk of developing an infection in chemotherapy patients given TPN (pooled P less than 0.0001) underscores the importance of demonstrating significant benefits in randomized trials before TPN is used routinely in these patients. PMID- 3091242 TI - Immunocytochemical evidence for gastric proteases in adenocarcinoma of the stomach. AB - When anti-sera to bovine pepsinogen and chymosin (rennin) was used, immunoreactive tumor cells were found in 12 of 23 gastric adenocarcinomas irrespective of the tumor subtype, degree of differentiation, or the presence or absence of intestinal metaplasia in the adjacent gastric mucosa. Nine of ten lymph node metastases contained immunoreactive tumor cells. Except for focal positively staining acini in Brunner's glands the antibodies did not stain normal small intestine or areas of intestinal metaplasia. Although intestinal metaplasia is a predisposing factor in gastric carcinoma it may be irrelevant to its histogenesis and differentiation. Instead, the mucus neck cells, being the stem cells of the normal gastric mucosa, may be the target of malignant transformation in gastric carcinoma. PMID- 3091244 TI - A syndrome of microangiopathic hemolytic anemia, renal impairment, and pulmonary edema in chemotherapy-treated patients with adenocarcinoma. AB - Chemotherapy is frequently used to treat adenocarcinoma. Thirty-nine cases are reviewed in which the patients developed a hemolytic-uremic-like syndrome, apparently in response to chemotherapy. About 44% of the patients had gastric adenocarcinoma, and 82% had received mitomycin C. Most patients (75%) developed the syndrome 6 to 12 months after starting chemotherapy, and 60% were in remission. Severe microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment were each noted in about 90% of the cases. Neurologic symptoms were usually absent, but 49% of the patients developed adult respiratory distress syndrome (ARDS). The overall case fatality rate was 72%; those patients with ARDS had a 95% mortality rate, while 50% of those without ARDS survived. The half-life of survival of those who ultimately died was 2 months. Treatment is unsatisfactory, although steroids and plasmapheresis may prolong survival. PMID- 3091245 TI - Comparison of reduced glutathione with 2-mercaptoethane sulfonate to prevent cyclophosphamide-induced urotoxicity. AB - Since the usefulness of high-dose cyclophosphamide is often limited by hemorrhagic cystitis, and the use of sulfhydryl-containing compounds prevents this side effect, this study was carried out to compare the uroprotective efficacy of 2-mercaptoethane sulfonate (MESNA) with that of reduced glutathione. In experimentally cyclophosphamide-induced urotoxicity in mice, the protective efficacy and potency of these thiols were similar, since both agents afforded complete protection in the same dose range. This finding suggests that these compounds are suitable sources of urinary thiols. Although the rationale for the clinical use of these protectors is similar, glutathione may have therapeutic advantages over MESNA because of a wider margin of safety and multiple protective actions displayed by the tripeptide thiol. PMID- 3091246 TI - Hyponatremia and other toxic effects during a phase I trial of recombinant human gamma interferon and vinblastine. AB - Recombinant human gamma interferon (Biogen) and vinblastine were administered in a phase I study. Side effects included fever and chills, nausea and vomiting, acute symptomatic hyponatremia, reversible myelosuppression, hepatitis, transient hypotension, congestive heart failure, renal insufficiency, and nonselective proteinuria. In most patients, additional host factors contributed to these toxic effects. Side effects occurred despite dose reduction; therefore, protocol accrual was prematurely closed. No correlation between serum concentrations and toxicity was noted. Median serum vinblastine concentration was 1.04 ng/ml; median serum interferon concentration was 17.3 IU/ml. PMID- 3091247 TI - Effects of membrane fluidity changes on lectin binding in Tetrahymena pyriformis. PMID- 3091248 TI - Effect of mitomycin C on energy metabolism: essential role of aerobic glycolysis in proliferation of L cells. PMID- 3091249 TI - Electron-microscopic cytochemistry of the catecholaminergic innervation of TRH neurons in the rat hypothalamus. AB - The catecholaminergic innervation of thyrotropin-releasing hormone (TRH) neurons was examined by use of a combined method of 5-hydroxydopamine (5-OHDA) uptake or autoradiography after intraventricular injection of 3H-noradrenaline (3H-NA) and immunocytochemistry for TRH in the same tissue sections at the electron microscopic level. TRH-like immunoreactive nerve cell bodies were distributed abundantly in the parvocellular part of the paraventricular nucleus (PVN), in the suprachiasmatic preoptic nucleus and in the dorsomedial nucleus of the rat hypothalamus. In the PVN, a large number of immunonegative axon terminals were found to make synaptic contact with TRH-like immunoreactive cell bodies and fibers. In the combined autoradiography or 5-OHDA labeling with immunocytochemistry, axon terminals labeled with 3H-NA or 5-OHDA were found to form synaptic contacts with the TRH immunoreactive nerve cell bodies and fibers. These findings suggest that catecholamine-containing neurons, probably noradrenergic, may innervate TRH neurons to regulate TRH secretion via synapses with other unknown neurons in the rat PVN. PMID- 3091251 TI - Determination of human factor VIII (AHG-associated protein)--antigen in endothelial cells from Xenopus laevis (XTH cells). Evaluation of a sensitive ELISA technique. AB - AHG-associated protein (AHG-a.p.), the antigen of the blood-clotting factor VIII complex, is a specific endothelial cell marker. Primary (p-XTH) and established (XTH-2) endothelial cells from the hearts of Xenopus laevis tadpoles were assayed for the presence of this marker by means of immunological cross-reaction (recognition of common antigenic sites) with antiserum against human AHG-a.p. Radial immunodiffusion and rocket immunoelectrophoresis proved to be insufficiently sensitive, whereas immunofluorescence and a newly evaluated ELISA technique gave positive results. The very high sensitivity of the ELISA (less than 1/240,000 of the AHG-a.p. in 0.1 ml human standard plasma can be detected) and the removal of interfering proteins by gel filtration also revealed the presence of AHG-a.p. in the fetal calf serum used in the culture medium; earlier investigations into this subject by a one-step radioimmunoassay had reported negative results. Specially adapted XTH-2 cells were grown in a protein-and serum free hydrolysate medium in order to demonstrate the presence of a Xenopus-derived antigen that was immunoreactive with the anti-human AHG-a.p. PMID- 3091250 TI - Morphology of tight junctions in the ciliary epithelium of rabbits during arachidonic acid-induced breakdown of the blood-aqueous barrier. AB - A reversible breakdown of the blood-aqueous barrier in the iridial processes of rabbits has been induced by arachidonic acid as demonstrated by the passage of horseradish peroxidase at places through the tight junctions. Freeze-fracture images reveal very discontinuous P-face ridges. However, the analysis of complementary replicas demonstrates that discontinuities of P-face ridges are always complemented by particles or short bars found in the E-face furrows. Though the problem exists of correlating freeze-fracture images of the junctional structure to the focal passage of horseradish peroxidase, the data suggest that the discontinuities of P-face ridges cannot be the structural counterpart of the passage of horseradish peroxidase. Alternative pathways of horseradish peroxidase are discussed in context with the offset bifibrillary model of the junction. PMID- 3091252 TI - Light-microscopic immunocytochemical localization of growth hormone-releasing factor in the human hypothalamus. AB - The distribution of growth hormone-releasing factor (GRF)-like immunoreactivity in the human hypothalamus was studied by light-microscopic immunocytochemistry. With antibodies that we developed against synthetic human pancreatic GRF (hpGRF), we localized GRF immunoreactivity in neuronal cell bodies that were observed only in the infundibular (arcuate) nucleus. Immunostained nerve fibers were found in large numbers in the neurovascular zone of the median eminence, in the proximal portion of the pituitary stalk and in periventricular areas. These localizations are in agreement with those of studies recently performed in other species and strongly suggest that GRF can be released into the capillaries of the pituitary portal plexus to reach the anterior pituitary gland. The projections of GRF neurons in extra-infundibular regions suggest that GRF can also act as a neuromodulator or neurotransmitter in the hypothalamus. PMID- 3091253 TI - [Recent progress in studies of brucellosis in deer]. PMID- 3091254 TI - [Types and epidemiological features of acute viral hepatitis in children under 15 in Xian City]. PMID- 3091255 TI - [Scarlet fever due to type group A hemolytic Streptococcus infection and its T antigen typing]. PMID- 3091256 TI - [Detection of antigens and antibodies of epidemic hemorrhagic fever virus in experimental albino rats in Guangzhou City]. PMID- 3091257 TI - Comparison of pharmacodynamic effects and plasma levels of oral and rectal ergotamine. AB - Plasma levels and the vasoconstrictive effect of 1 mg ergotamine tartrate given as tablets or suppositories were compared. In a crossover study, eight male volunteers received tablets or suppositories containing ergotamine in a drug combination (Anervan) and, as a control, suppositories without ergotamine. Blood sampling and measurement of toe-arm systolic gradients with a strain-gauge technique were done for up to 6 h and again after 24 h and 48 h. Only 29 of 160 blood samples contained detectable (greater than 0.1 ng/ml) amounts of ergotamine, and kinetic comparison could not be performed. Only ergotamine containing suppositories caused a significant (p less than 0.008) decrease in toe arm systolic gradient which was significantly different (p less than 0.003) from the effects of ergotamine tablets and control suppositories. Rectal ergotamine is thus more biologically active, for the factor used, than oral ergotamine. We suggest that a rectal dose of 1 mg ergotamine tartrate should be tried as the initial dose in the treatment of migraine attacks. PMID- 3091258 TI - Multiple nuclear factors interact with the immunoglobulin enhancer sequences. AB - To characterize proteins that bind to the immunoglobulin (Ig) heavy chain and the kappa light chain enhancers, an electrophoretic mobility shift assay with end labeled DNA fragments was used. Three binding proteins have been found. One is NF A, a factor found in all tested cell types that binds to the octamer sequence found upstream of all Ig variable region gene segments and to the same octamer in the heavy chain enhancer. The second, also ubiquitous, protein binds to a sequence in both the heavy chain and the kappa enhancers that was previously shown to be protected from methylation in vivo. Other closely related sites do not compete for this binding, implying a restriction enzyme-like binding specificity. The third protein binds to a sequence in the kappa enhancer (and to an identical sequence in the SV40 enhancer) and is restricted in its occurrence to B cells. PMID- 3091259 TI - Local function of the Notch gene for embryonic ectodermal pathway choice in Drosophila. AB - Mutations at the Notch locus affect the fate of cells in the neurogenic region of the Drosophila embryo so that epidermal precursors become neuroblasts. We have analyzed the cellular requirements for wild-type Notch gene function by means of genetic mosaics, using a cuticle marker to distinguish hypodermal cell genotype. Cells that were genotypically Notch never gave rise to hypoderm within the neurogenic region of mosaic embryos. Mosaic dividing lines within the neurogenic region juxtapose N+ hypoderm with regions of neural hypertrophy. This autonomous action of Notch in hypodermal cells is consistent with a local function of the protein during neurogenesis. Comparison of clone distribution in Notch mosaics and controls suggests that islands of wild-type hypodermal cells fail to differentiate cuticle. PMID- 3091260 TI - Analysis of CD3-antibody-mediated inhibition of T-cell activation. AB - In this study the influence of a non-mitogenic anti-CD3 antibody on accessory cell-dependent antigen and mitogen-induced T-lymphocyte proliferation has been investigated. The antibody was found to completely inhibit PHA, Con A, PWM, and tetanus toxoid stimulation, with no effect on the proliferation induced by the calcium ionophore A23187. VIT3 completely abrogated the production of IL-2 by lectin-stimulated T cells. It had no effect, however, on the IL-2-dependent proliferation of preactivated T-cell blasts. In addition, the antibody was able to elevate free cytoplasmic Ca2+ levels within minutes after the addition to T cells. Detailed time kinetic analyses revealed that the time interval critical for inhibition was significantly dependent on the interaction between T cells and accessory cells. Under standard conditions, in the presence of 10% non-T cells as accessory cells 50% inhibition was still achieved when VIT3 was added to PHA stimulated T cells as late as 8 hr after the onset of culture. Delayed addition or a decrease in the number of added accessory cells significantly prolonged this time period. Lectin-stimulated T cells can thus obviously be inhibited via CD3 as long as they have not received all signals including those delivered by accessory cells. Although the underlying mechanisms are not clear so far, the observation that VIT3 at the same time triggers an early cytoplasmic Ca2+ response might indicate that it thereby actively interferes with antigen and lectin-initiated activation processes. PMID- 3091261 TI - Regulation of cytotoxic lymphocyte precursors. II. The effect of interleukin-2 and interferon-gamma on the apparent specificity of effector cells. AB - The influence of lymphokines on the frequency and specificity of antigen-induced cytolytic T cells was investigated. Removal of an acid-labile factor(s) from supernatants produced by concanavalin A (Con A)-stimulated rat splenocytes was shown to increase the specificity of cytolytic T-cell clones as determined by their ability to distinguish between antigen modified and unmodified target cells. The overall frequency of cytolytic T cell precursors (antigen specific as well as nonspecific) was reduced in the presence of acid-pretreated rat Con A supernatant as compared to untreated rat Con A supernatant. Neither the addition of interleukin 2 nor interferon-gamma could substitute for this acid-labile factor. These data indicate that an additional lymphokine(s) contributes to the in vitro activation of nonspecific killer cells. PMID- 3091262 TI - Recombinant tumor necrosis factor: species specificity for a variety of human and murine transformed cell lines. AB - Tumor necrosis factor (TNF) exhibits cytotoxic or cytostatic activity on a wide range of animal and human transformed cell lines. Using pure, recombinant human and mouse TNF, we examined the degree of species specificity of the in vitro TNF activity on a variety of human and murine transformed cell lines. This species specificity was studied for the TNF activity alone or in synergism with IFN gamma. Recombinant human and mouse TNF behave remarkably similarly regarding the in vitro cytolytic/cytostatic activity. However, a certain degree of species specific preference could be revealed as human cell lines needed a higher concentration of recombinant mouse TNF than of recombinant human TNF to attain a similar effect, while on mouse cells the reverse was true. Also, synergism with IFN-gamma seemed more effective when the target cell was treated with homologous TNF. PMID- 3091263 TI - Evidence by radioimmunoassay that mitogen-activated human blood mononuclear cells secrete significant amounts of light chain Ig unassociated with heavy chain. AB - The culture supernatant (CS) Ig of PWM-activated human blood mononuclear cells was quantitatively determined using a panel of nanogram-sensitive radioimmunoassays (RIAs) that separately measured IgG, IgM, IgA, total kappa Ig, and total lambda Ig. After initial RIA quantitation, separate CS aliquots were exposed to either a polyisotypic anti-heavy (H) chain or a nonimmune IgG solid phase immunoabsorbent, and then reassayed for Ig content. The reassay results revealed that the anti-H chain-absorbed CS aliquots retained significant amounts of kappa and lambda Ig, but yet had a virtual absence of isotypic IgG, IgM, and IgA. Comparisons of the absorbed CS aliquots suggested that as much as one-fourth to one-third of the total secreted L chain Ig in PWM-activated cultures lacked RIA-detectable associated H chain. This unexpected finding of significant amounts of unbound L chain in mitogen-stimulated cultures raises important theoretical issues relative to the functional role of secreted free L chain and the prospects that free L chain levels may represent useful quantitative markers of B-cell stimulation. PMID- 3091264 TI - Different effects of IL-2 addition or antibody crosslinking on T-cell subset stimulation by CD3 antibodies. AB - The effect of exogenous recombinant interleukin-2 (IL-2) or of antibody crosslinking on the activation of human T-cell subsets by IgG2a (OKT3/BMA030), IgG1 (Leu4 and UCHT1), or IgG2b (BMA031) anti-T3 antibodies (CD3) was investigated. In so-called nonresponder cultures as well as in monocyte-depleted cell cultures addition of IL-2 increased the CD3-induced activation and proliferation of T4 and T8 cell subsets. Relatively more T8 than T4 cells were stimulated by antibody binding and IL-2. Crosslinking the cell-bound CD3 antibodies by plastic bound goat anti-mouse antibodies activated both T-cell subsets optimally and increased the IL-2 production of the IgG1-CD3 stimulated cultures. The data show that T cells (T8 greater than T4) can be stimulated by CD3 antibody binding and IL-2, but that crosslinking the cell-bound CD3 antibodies is crucial for optimal T4 cell stimulation and IL-2 production. PMID- 3091265 TI - Dual effects of pertussis toxin on lymphoid cells in culture. AB - Pertussis toxin (Ptx), a component of Bordetella pertussis, is responsible for many of the biological activities of this bacterium, including its potent adjuvant capacity. In attempt to better understand the Ptx activity on the immune response in vivo, we have examined the effect of Ptx on certain lymphoid cell responses in vitro which could be targets for the adjuvant activity of this molecule. Ptx was found to stimulate a variety of cell responses which include (a) increased production and release of interleukin-1 (IL-1) by human monocytes and murine macrophages; (b) co-mitogenesis, in combination with IL-1, in cultures of murine thymocytes; (c) mitogenesis in cultures of various peripheral lymphocytes; (d) increased production of IL-2 in cultures of human blood lymphocytes and rodent splenocytes; and (e) elevated release of IL-3 in cultures of murine spleen cells. In addition to its stimulatory effects, however, Ptx was found to inhibit responses of both mononuclear phagocytes and lymphocytes to other stimuli. Most activities of Ptx in vitro were achieved at the optimal concentration range of 1-10 micrograms/ml, which is 100-1000 times higher than that showing adjuvant effects in vivo. Possible explanations for the dual effect of Ptx and for the discrepancy in doses optimal for the effects in vivo and in vitro are discussed. PMID- 3091266 TI - Production of auto-anti-idiotypic antibody during the normal immune response. XII. Enhanced auto-anti-idiotypic antibody production as a mechanism for apparent B-cell tolerance in rabbits after feeding antigen. AB - Rabbits fed trinitrophenylated bovine serum albumin (TNP-BSA) generated fewer anti-TNP plaque-forming cells but greater numbers of hapten (TNP)-augmentable IgM and IgG PFC following immunization with TNP-Ficoll or TNP-Brucella abortus than did animals not previously fed antigen. Spleen and mesenteric and bronchial lymph nodes were similarly affected. In addition more auto-anti-idiotype (Id) antibody (anti-anti-TNP) was eluted by hapten from spleen cells of antigen-fed rabbits than from spleen cells of control rabbits not prefed antigen. Gel filtration studies ruled out the possibility that the Id binding activity in the eluates was due to immune complexes. The isotype of the anti-Id was IgG except in one rabbit where it was IgM. The results are consistent with the interpretation that the production of auto-anti-Id antibody is one of the factors responsible for the specific depression of the IgM and IgG immune responses which follows antigen feeding. In contrast the antigen feeding resulted in priming for an IgA anti-TNP response without detectable hapten-augmentable IgA PFC. PMID- 3091267 TI - Inhibitory effect of cyclosporin A on the OKT3-induced peripheral blood lymphocyte proliferation. AB - In this paper we studied the effect of cyclosporin A (CyA) on interleukin 1 (IL 1) and interleukin 2 (IL-2) production and on IL-2 receptor expression by human peripheral blood lymphocytes induced to proliferate following OKT3 monoclonal antibody stimulation. CyA inhibited T-cell proliferation in a dose-dependent manner and its effect was inversely correlated with the entity of the mitogenic signal. The drug reduced not only IL-2 synthesis but also IL-1 production. CyA was also found to be able to inhibit the expression of IL-2 receptors on T cells. By supplementing with IL-1 and/or IL-2 the cultures carried out in the presence of CyA, it became evident that the inhibition of IL-2 production mainly depended on the CyA-induced reduction of IL-1 synthesis. Thus the IL-2 production by "resting" T cells had to be considered as an IL-1-dependent event. In addition it was found that the presence of IL-1 constituted a crucial requirement for the induction and the positive modulation of IL-2 receptor expression. Although IL-2 could play a role in facilitating the expression of IL-2 receptors, its effectiveness to do so depended on the presence of IL-1. In conclusion, CyA is to be considered not only as a potent immunodepressive drug but also as a valuable tool for the study of T-cell activation and proliferation. PMID- 3091268 TI - A functional analysis of the T-cell defect in MRL-lpr mice. AB - Autoimmune MRL-lpr mice have a defect in antigen-specific T-cell proliferation. Our studies indicate that this defect is caused by the massive expansion in MRL lpr mice of a unique T-cell subset which is unresponsive to antigenic signals. Pharmacologic doses of PGE1 suppress this lymphoid hyperplasia and thus prevent loss of T-cell functions by preventing numeric dilution of normal T cells by defective T cells. The inability of the unique subset of T cells to respond to antigenic signals cannot be corrected by the addition of interleukin 2 (IL-2), implying that additional cellular properties are required to initiate proliferation. While the vast majority of freshly harvested MRL-lpr T cells lack IL-2 receptors (R) as measured by anti-IL-2R monoclonal antibody staining, a large fraction of nonstimulated, cultured (48 hr) MRL-lpr T cells, but not MRL-++ T cells, express IL-2R. These experiments suggest that MRL-lpr cells are activated in vivo but an undefined suppressive influence prevents detection or expression of IL-2R until these cells are explanted and cultured. PMID- 3091269 TI - Thymic lymphocytes. III. Cooperative phenomenon in the proliferation of thymocytes under Con A stimulation. AB - In the present paper, the response of thymocytes to Con A is analyzed in terms of a cooperative phenomenon between medullary thymocytes, cortical thymocytes, thymic accessory cells, and interleukin 2. Medullary thymocytes respond spontaneously to Con A and produce IL-2. The addition of exogenously produced IL 2 enhances their proliferation. Small numbers of cortical (PNA+) thymocytes do not respond to Con A, even in the presence of IL-2-containing supernatant. By increasing the number of PNA+ cells per well, sensitivity to Con A and IL-2 appears. This response may be linked either to the increase in a minor PNA+ responding population and/or to the enhanced contamination by medullary thymocytes and macrophages in non-responding PNA+ thymocyte population. In this hypothesis, either the contaminating cells respond by themselves and/or cooperate with PNA+ cells to induce their proliferation. Coculture of non-responding low numbers of PNA+ thymocytes with Con A- and IL-2-containing supernatant in the presence of PNA- cells containing thymic medullary thymocytes and macrophages always produces a higher response than that of each individual population. These results show that a cooperative phenomenon occurs in the cocultures of PNA+ and PNA- thymic cells. We can show using PNA+ and PNA- thymocytes with different Thy 1 alleles, that indeed both PNA+ and populations participate PNA-thymocytes with different Thy 1 alleles, that indeed both PNA+ and PNA- populations participate in the generation of proliferating cells. We can demonstrate, by lysis experiments with monoclonal antibodies and complement that at the end of coculture, most of the proliferating cells are Lyt 1+, and part are Lyt 2+ or L3T4+. We discuss the fact that the phenotype of the cells after activation does not allow us to deduce the phenotype of their precursors. Lysis of Ia+ cells prior to coculture, reduces the level of the proliferative response but does not modify the percentage of cooperation produced by the coculture. Cooperation with medullary mature thymocytes or the presence of active Ia- accessory cells possibly able to convert to Ia expression during coculture experiments may account for these results. PMID- 3091270 TI - Human T-lymphocyte chemotactic activity: nature and production in response to antigen. AB - Previous studies have shown that supernatants from concanavalin A-stimulated human peripheral blood mononuclear cells and isolated Leu-2 suppressor/cytotoxic T cells are chemotactic for Leu-3 helper/inducer T cells. The current study shows that lymphocyte chemotactic factor (LCF) is also produced following antigen (tetanus toxoid) challenge of mononuclear cells obtained from recently immunized human donors. LCF was detected in 24-hr supernatants from mononuclear cells challenged with tetanus and was produced maximally at 48 hr. Tetanus toxoid challenge of mononuclear cells obtained from individuals whom had not received a tetanus immunization for 7 to 10 years prior to testing showed little or no production of LCF. Serial studies of these individuals following a tetanus booster immunization showed that LCF was produced by antigen-challenged mononuclear cells obtained 1-5 days postimmunization, was produced optimally 5-15 days postimmunization, and was still produced by antigen-challenged mononuclear cells obtained 6 weeks later. Fractionation of mononuclear cells from immunized donors into glass wool nonadherent lymphocytes, T lymphocytes, and non-T lymphocytes showed that tetanus-toxoid-induced LCF was produced by nonadherent lymphocytes and T cells but not non-T cells. Further fractionation of T lymphocytes into Leu-2 and Leu-3 T-cell subpopulations showed that LCF production by antigen-challenged isolated subpopulations was limited to the Leu-2 suppressor/cytotoxic T-cell subset. Characterization of both Con A and tetanus toxoid-induced LCF by gel filtration on Sephadex G-100 demonstrated the presence of two peaks of LCF corresponding to molecular weights of approximately 14,000 17,000 and 40,000-50,000. PMID- 3091272 TI - Effect(s) of lipopolysaccharide on lectin-induced T-cell activation. AB - The present study focuses on the effect of lipopolysaccharide (LPS) on the cellular events leading to T-cell activation by concanavalin A (Con A). Interleukin 2 (Il-2) production is much reduced in Con A-stimulated cultures of spleen cells derived from LPS-treated mice. This depressed Il-2 synthesis is not related to the eventual activity of LPS-activated suppressive B cells. Rather, it reflects an ineffective collaboration between adherent cells and T lymphocytes. The low level of Il-2 produced by LPS-sensitized spleen cells is sufficient for lectin-induced T-cell proliferation. Moreover, acquisition of responsiveness to Il-2 is unaltered by LPS. No strict correlation was found between the deficiency in Il-2 production and the inability of LPS-sensitized spleen cells to generate a thymus-dependent response. Less time (5 hr) is needed for LPS to exert its inhibitory effect on an anti-sheep red blood cell response than on Il-2 synthesis (at least 24 hr). Results are discussed in terms of cellular interactions implicated in a polyclonal T-cell response and with regard to the contribution of Il-2 to the LPS-induced immune unresponsiveness. PMID- 3091271 TI - Pertussigen enhances antigen-driven interferon-gamma production by sensitized lymphoid cells. AB - We have studied the effects on interferon-gamma (IFN-gamma) production of pertussigen, a protein toxin from Bordetella pertussis that augments and prolongs delayed-type hypersensitivity (DTH) reactions. Lymphoid cell suspensions from immunized mice were incubated with antigen or mitogen, and the culture supernatants were assayed for IFN-gamma. The production of IFN-gamma on exposure to specific antigen or concanavalin A was greatly enhanced if mice were given pertussigen at the time of immunization. There was no detectable IFN-gamma production when cells were exposed to saline or to an irrelevant antigen. The effect of pertussigen on antigen-driven IFN-gamma production correlated with its effect on the capacity of the same cell populations to transfer DTH. The enhanced IFN-gamma production by cells from mice given pertussigen could not be attributed to an increased antigen-presenting capacity of this cell population. Production of IFN-gamma was abolished if the cells were pretreated with emetine, but not with mitomycin C, and the release of IFN-gamma was not detected in the first 8 hr of culture. After immunization with pertussigen, IFN-gamma was produced by lymph node and spleen cells from 7 days onward and both cell types produced IFN-gamma until at least 30 days after immunization. It is suggested that the augmentation of antigen-specific IFN-gamma production may contribute to the prolonged DTH reactions induced by pertussigen in vivo. PMID- 3091273 TI - Definition by CB12 monoclonal antibody of a differentiation marker specific for human monocytes and their bone marrow precursors. AB - The CB12 monoclonal antibody, which reacts with a molecule expressed on monocytes, was characterized using human embryonic material as immunizer. Analysis of the monoclonal antibody at the phenotypic, molecular, and functional levels indicates that its reactivity is restricted to circulating monocytes and their precursors in the bone marrow, whereas it is undetectable on tissue macrophages. CB12 displays a pattern of reactivity compatible with that of a marker of monocyte differentiation. Preliminary data indicate a possible receptor role for the CB12 molecule. PMID- 3091274 TI - Distinct T-cell proliferative responses to 13762A rat mammary adenocarcinoma and derived clones. AB - We examined the in vitro responses of immune lymphocytes to the tumor antigens of the syngeneic rat mammary adenocarcinoma 13762A. This tumor readily metastasizes to lymph node and lungs and is poorly immunogenic. Rats were immunized with a highly immunogenic clone (18A) which was isolated as a spontaneous variant from the parental 13762A tumor. Clone 18A grew progressively in irradiated rats but regressed completely in normal rats. Animals immune to 18A tumor were also immune to parental 13762A. Lymphocytes obtained from the spleen and peritoneum of immune rats were tested for specific proliferation to parental 13762A tumor and clone 18A to determine whether similar cross-reactivity to these tumors occurred in vitro. We found an anatomical difference in localization of immune lymphocytes which reacted to the two tumor cell lines. Immune peritoneal exudate cells (PEC) responded strongly to clone 18A but poorly to 13762A, while immune spleen cells from the same animals responded predominantly to 13762A tumor. After 7 days culture, PEC proliferating in response to clone 18A contained 84-95% W3/25+ T helper cells, and only 5-8% OX8+ cytotoxic/suppressor cells, while analogous cultures of spleen cells responding to parental 13762A tumor consisted of 60-80% W3/25+ cells and 20-23% OX8+ cells. Immune spleen cell cultures stimulated with 13762A tumor generated cytotoxic lymphocytes which specifically lysed both parental 13762A and clone 18A cells. We conclude that despite cross-reactivity in vivo and in vitro, antigens present on 13762A and 18A tumor cells stimulated different subsets of immune T cells. PMID- 3091275 TI - Fc receptors on monocytes cause OKT3-treated lymphocytes to internalize T3 and to secrete IL-2. AB - Monocytes cause OKT3-treated T cells to secrete IL-2 and to lose cell surface T3. We have studied the fate of the "lost" T3. Immunofluorescence microscopy on permeabilized cells showed that monocytes induce T cells to internalize T3. Furthermore, experiments with radioiodinated T cells showed that the internalized T3 was not degraded and exhibited an unaltered polypeptide composition for at least 16 hr. The role of Fc receptors in inducing internalization was also investigated. Fc receptors were depleted from monocytes by allowing the phagocytes to spread on immune complexes. Such depleted monocytes exhibit a fourfold reduction in their ability to promote both internalization of T3 and production of IL-2. A comparable reduction is seen if F(ab')2 fragments of OKT3 were employed in place of intact IgG. Furthermore, monocyte Fc receptors that have been blocked by heat-aggregated human IgG also show much reduced capability for induction of OKT3-mediated T-cell proliferation. We therefore conclude that Fc receptors bind to the Fc domain of OKT3 and thereby cause OKT3-treated T cells to internalize T3 and become activated. PMID- 3091276 TI - Stimulation of mouse B cells by a factor that coisolates with T-cell proteoglycan. AB - We have isolated a factor that copurifies with chondroitin sulfate proteoglycan secreted by mouse splenocytes and some murine T-cell hybridomas. This factor will stimulate proliferation and plaque-forming cell differentiation of B lymphocytes from mouse spleens, even after T cells have been depleted (less than 2% Thy 1.2 bearing cells). Adherent macrophages enhance the activity of this factor, but their function can be replaced in macrophage- and T-cell-depleted populations by small concentrations of a protein mitogen from Salmonella typhimurium. The stimulatory fraction contains chondroitin sulfate, a major protein which has a molecular weight of 74,000 and a minor moiety at 50,000. Stimulatory activity of this material is destroyed by (i) boiling, (ii) mild alkali treatment, and (iii) protease digestion. It is unaffected by RNase and chondroitinase treatments, suggesting that the factor is a protein. Our data define a new B-cell stimulatory substance(s) and suggest that it may be associated with chondroitin sulfate proteoglycan secreted by immune cells. PMID- 3091277 TI - Analysis of the lipopolysaccharide-induced cytostatic activity of macrophages, by the use of synthetic models. AB - Informations on the structural features implicated in the macrophage-dependent cytostatic activity of "lipid A" preparations were obtained by the use of 15 synthetic glycolipids. Four structural requirements were identified: the presence of a reducing glucosamine unit; the presence of a free hydroxyl group on amide linked 3-hydroxytetradecanoic acids, and the absence of free hydroxyl groups at positions 3 and 6 of the glucosamine. The monosaccharide resembling the reducing unit of the "lipid A backbone," which fulfills these criteria, had the highest cytostatic activity, whereas the compound possessing the substitution pattern of the nonreducing moiety was inactive. PMID- 3091278 TI - Release of eicosanoids from cultured rat aortic endothelial cells; studies with arachidonic acid and calcium ionophore A23187. AB - The release of prostanoids from the three different vascular cell types derived from rat aortic explants has been studied in vitro. Under resting conditions and when incubated with exogenous arachidonic acid (AA, 10 microM), the endothelial cells (EC) produced the highest concentration of prostacyclin (PGI2 PGE2 PGF2 alpha TxA2). In contrast, PGE2 was the major prostanoid produced by the smooth muscle cells and fibroblasts. Pretreatment of EC with aspirin (10 microM) or indomethacin (10 microM) effectively inhibited the production of prostanoids by these cells. Incubation with the calcium ionophore A23187 (10 microM) did not stimulate production of PGI2 or leukotriene B4 (LTB4) by EC. However, treatment of EC with a combination of A23187 and AA led to production of amounts of both PGI2 and LTB4 which were greater than the summed values for the different drug treatments. These findings indicate that the concentration of substrate, AA, is a limiting factor in prostanoid formation by these cultured vascular cells but that rat EC are relatively poor in the enzymes required for leukotriene formation. PMID- 3091279 TI - Male fertility regulation: recent advances. AB - Acceptable antifertility drugs for men are proving difficult to produce. Such drugs must aim to achieve complete azoospermia over a long period. This requirement may be relaxed only if it can be shown that the residual sperm produced by men whose spermatogenesis has been suppressed by antifertility drugs to oligospermia are incapable of fertilizing ova. Hormonal methods involving suppression of the secretion of gonadotrophin hormones by the pituitary gland invariably require androgen supplementation, and the use of steroids either alone or in combination requires careful monitoring for their side-effects. A chemical (non-hormonal) approach involving the incapacitation of sperm in the epididymis has been shown to be feasible in animal studies using alpha-chlorohydrin and 6 chloro-6-deoxy sugars, although such compounds cannot be developed for human use because of their toxicity. Immunological approaches have the inherent problem of delivery of the antibody to the target. While the search for new and safer chemical and hormonal approaches goes on, the recent evidence that vasectomy offers a safe surgical option leaves responsible men with some choice to add to the condom. PMID- 3091280 TI - Preclinical toxicology, pharmacokinetics and formulation of N2,N4,N6 trihydroxymethyl-N2,N4,N6-trimethylmelamine (trimelamol), a water-soluble cytotoxic s-triazine which does not require metabolic activation. AB - N2,N4,N6-Trihydroxymethyl-N2,N4,N6-trimethylmelamine (Trimelamol) is a water soluble synthetic s-triazine which, unlike hexamethylmelamine (HMM) and pentamethylmelamine (PMM), does not require metabolic activation. The physico chemical characteristics of Trimelamol were studied with the aim of overcoming the problems of chemical instability, low solubility and polymerisation which had hindered the development of the drug for clinical use. Trimelamol had similar activity to PMM against the murine PC6 plasmacytoma, but enhanced activity with respect to PMM against the Walker 256 carcinosarcoma in the rat, a species which metabolizes PMM less efficiently. Pharmacokinetic studies in mouse, rat and man did not show the major species differences characteristic of PMM. The drug exhibited similar toxicity to PMM against rodents, but had virtually no neurotoxicity. The potential advantages of Trimelamol over previously tested melamines are discussed. PMID- 3091281 TI - Metabolism of the renal carcinogen FNT by peroxidases. AB - Formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]-hydrazide (FNT) is a renal carcinogen in the rat. The peroxidative activity of prostaglandin H synthase oxidizes FNT into a reactive intermediate which forms 5-(S)-substituted thioether conjugates with glutathione and N-acetylcysteine. These conjugates are also formed during horseradish peroxidase oxidation of FNT. The conjugate was identified by the combined results of comparative u.v./vis. spectrophotometry, chromatographically-assisted hydrodynamic voltammetry and proton n.m.r. spectroscopy. The relative rate of PHS metabolism of FNT was similar to that observed with benzidine and 5-fold faster than ANFT, its 5-nitrofuro-2 aminothiazole analogue. These results indicate that the pathogenic effects of FNT may be caused by its peroxidative activation and that cellular thiols may attenuate the toxic effects of FNT by conjugate formation. PMID- 3091282 TI - Retinoic acid enhancement of an early step in the transformation of mouse epidermal cells in vitro. AB - Retinoic acid has been reported to act as an inhibitor and as an enhancer of mouse skin carcinogenesis in vivo. However, no in vitro cell transformation model has been reported to be sensitive to both effects. In an attempt to provide such a model, the effect of retinoic acid on an early step in carcinogen-induced transformation of mouse epidermal cell line 271c was measured using a recently described assay. The step observed is altered response to extracellular Ca2+ as an epidermal terminal differentiation signal. In six out of twelve experiments retinoic acid increased the frequency of altered colonies resulting from treatment with three chemical carcinogens. The enhancement effect was stronger after DMBA treatment than MNNG or MCA, resulting in up to a 13.7-fold increase in the frequency of colonies exhibiting altered terminal differentiation (TF). On the other hand, up to a 10-fold decrease in TF was observed in other experiments. Both the enhancement and inhibitory effects were greater at the higher doses of retinoic acid tested in the range of 10(-10) - 10(-7) M. Variations in cloning efficiency or surviving colony density did not account for the effects on TF. Enhancement effects tended to be observed at lower doses of carcinogen, or in experiments in which TF resulting from treatment with carcinogen alone was in the lower range observed. However, the factors determining each effect have yet to be defined. The enhancement effect of retinoic acid was not merely suppression of the phenotypic endpoint of the in vitro assays, because treatment of carcinogen altered cells with retinoic acid or TPA in vitro also enhanced their tumorigenicity in vivo compared to acetone controls. These findings suggest that studies of the determinants of retinoid activity should be a prerequisite to their use in chemoprevention. PMID- 3091283 TI - Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis. AB - Using as a criterion the inhibition of serum beta-glucuronidase activity, dietary calcium D-glucarate is shown to serve as an efficient slow-release source in vivo of D-glucaro-1,4-lactone, the potent endogenous inhibitor of this enzyme. Using the 7,12-dimethylbenz[a]anthracene model of mammary tumor induction in rats it is shown for the first time that feeding the rats calcium D-glucarate-supplemented diet after treatment with the carcinogen, inhibits tumor development by over 70%. Supportive evidence is presented for the theory that calcium D-glucarate inhibits or delays the promotion phase of mammary carcinogenesis by lowering endogenous levels of estradiol and precursors of 17-ketosteroids. Therefore, dietary glucarate can be used to lower blood and tissue levels of beta-glucuronidase, and in turn of those carcinogens and promoting agents which are excreted, at least in part, as glucuronide conjugates. PMID- 3091284 TI - Hyperthermia and phorbol ester tumor promotion in mouse skin. AB - In a two-stage skin tumorigenesis protocol [7,12-dimethylbenz[a]anthracene (DMBA) initiation followed by twice weekly 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion], SENCAR mice developed an average of approximately 8.5 papillomas per animal. Hyperthermia treatments of the initiated skin (44 degrees C, 30 min) immediately before or after each TPA application (for 90 days) reduced papilloma frequency 80-90%. Animals whose initiated skin was made thermo-tolerant at the time of TPA application (by hyperthermia treatment 24 h prior to each application of promoter) showed slightly less protection (approximately 70% reduction in frequency). Multiple 44 degrees C hyperthermia treatments alone (27 X, twice a week) had no promoting activity in DMBA-initiated skin. The usual responses of skin to TPA promotion, including an increase in dark cells, epidermal thickening, reddening and erosion were all suppressed in animals treated with hyperthermia near the time of TPA application. The effect of hyperthermia on tumorigenesis was at the promotion stage and the survival of initiated cells was not affected, since the normal number of papillomas was produced when TPA promotion was delayed until after the multiple (27 X, twice a week) hyperthermia treatments were completed. Hyperthermia treatments (44 degrees C, 30 min, twice weekly for 90 days) given near the time of TPA application also suppressed the incidence of carcinomas appearing within 300 days. About 40% of the DMBA-initiated, TPA promoted animals developed a carcinoma, compared with only approximately 10% of a similar group which received hyperthermia treatments near each TPA application. Papillomas appearing in spite of hyperthermia treatments during promotion were not more likely to progress into carcinomas than those appearing in unheated animals. Such hyperthermia treatments given to animals bearing pre-existing papillomas did not markedly alter the subsequent development of carcinomas compared with unheated controls. The results demonstrated that 44 degrees C hyperthermia applied near the time of TPA promotion acted as a powerful antipromoter and suppressed the appearance of both papillomas and carcinomas, apparently by acting at an early stage of promotion. PMID- 3091285 TI - In vivo formation and persistence of DNA adducts in mouse and rat skin exposed to (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and (+/-)-7 beta,8 alpha dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. AB - The in vivo DNA adduct formation of (+/-)-trans-7,8-dihydroxy-7,8 dihydrobenzo[a]pyrene (BPD) and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) were compared and the persistence and disappearance of the adducts in both mouse and rat epidermis determined. BPD (100 nmol/mouse in 150 microliter acetone and 200 nmol/rat in 300 microliter acetone) and anti-BPDE (77 nmol/mouse in 150 microliter tetrahydrofuran and 154 nmol/rat in 300 microliter tetrahydrofuran) were topically applied to 50-day-old male Swiss mice and 35-day-old Wistar rats. To improve the identification of the DNA adducts formed, an acid hydrolysis technique was used to convert the BPD- and anti-BPDE-deoxyribonucleoside adducts formed in mouse and rat skin to BP tetrols. The modified deoxyribonucleosides and BP tetrols obtained by hydrolysis of adducts were isolated by reverse-phase h.p.l.c. At approximately similar doses per unit area of treated skin, the initial total binding of these compounds to epidermal DNA and the level of modified deoxyribonucleosides was approximately 6-fold lower in rat skin epidermis than in mouse skin epidermis. Similar ratios of (+/-)-anti-BPDE deoxyguanosine (dGuo) to (+/-)-syn-BPDE-dGuo adducts (5.7 and 6.1, determined by h.p.l.c. analysis of BP tetrols obtained by hydrolysis of modified dGuo) were found in both mouse and rat epidermis a short time (6 h) after topical application of (+/-)-trans-BPD. Three hours after topical application of (+/-) anti-BPDE, the ratios of BP-7,10/8,9-tetrol to 7/8,9,10-tetrol were 9:1 in mouse epidermal DNA and 6:1 in rat epidermal DNA. One and three weeks after application of these two compounds, only (+)-anti-BPDE-dGuo was detected in mouse epidermis; 2 and 0.2% of the initial (+)-anti-BPDE-dGuo level was found to persist in the epidermal DNA from BPD- and anti-BPDE-treated mice respectively. No DNA adducts were detected in rat epidermis 3 weeks after BPD and anti-BPDE treatment. Thus, 3 weeks after topical application of BPD and anti-BPDE to mouse and rat skin, the DNA adducts completely disappeared from rat epidermis while they persisted in mouse epidermis. The results suggest that: the persistence of (+)-anti-BPDE-dGuo may be related to carcinogenesis in mouse epidermis by BPD and anti-BPDE; the complete disappearance of the anti-BPDE-dGuo adduct may also account in part for the relative resistance of tissue from this species to the carcinogenic action of benzo[a]pyrene. PMID- 3091287 TI - Enhancement of thrombolysis with tissue-type plasminogen activator by pretreatment with heparin. AB - The effect of pretreatment with heparin on lysis of arterial thrombi by tissue type plasminogen activator (rt-PA) was studied in 19 dogs. Copper coil-induced carotid artery thrombi were weighed, inserted into the femoral arteries, and exposed to a 15 min infusion of rt-PA at 10 micrograms/kg/min either with (n = 6 thrombi) or without pretreatment with a 200 unit/kg bolus of heparin (n = 6 thrombi). The infusion of rt-PA without pretreatment reduced the thrombus weight by 27.6 +/- 7.4%, while infusion of rt-PA with pretreatment reduced it by 79.1 +/ 12.3% (p less than .0001). To test the hypothesis that heparin enhanced thrombolysis by preventing continued incorporation of new fibrin into the thrombus during thrombolysis we repeated the experiments using pretreatment with 8 U/kg of ancrod, which rapidly depletes fibrinogen. Pretreatment with ancrod (n = 6 thrombi) depleted fibrinogen and enhanced the lytic effect of rt-PA to a similar degree as pretreatment with heparin, resulting in a 67.6 +/- 12.3% (NS) decrease in thrombus weight. We conclude that heparin significantly enhances the thrombolytic effect of rt-PA, probably by preventing new fibrin formation and its incorporation into the thrombus during lysis. PMID- 3091286 TI - Altered spectrum of nitroglycerin action in long-term treatment: nitroglycerin specific venous tolerance with maintenance of arterial vasodepressor potency. AB - The study of venodilator tolerance to nitroglycerin has been complicated by reflex compensation and by problems in analyzing venous tone in the presence of multiple determinants of venous pressure. We assessed venous tone as total effective vascular compliance (TEVC) under autonomic blockade in six dogs, in the nontolerant state, and during a 5 day infusion of nitroglycerin (1.5 micrograms/kg/min). Under long-term treatment, baseline TEVC was unaffected and the nitroglycerin dose-response relationship for TEVC was shifted to greater than 10-fold higher doses, whereas baseline mean arterial pressure (MAP) was lowered by 17 +/- 3 mm Hg without any shift in nitroglycerin responsiveness. This lowering of MAP was observed only after autonomic blockade. In six additional dogs instrumented with aortic flow probes, nitroglycerin (1.5 micrograms/kg/min) induced a 15 +/- 1% decline in peripheral vascular resistance (PVR) under autonomic blockade, but with reflexes intact these dogs showed no change in PVR and a 21 +/- 10% increase in norepinephrine release rate. We conclude that modest long-term exposure to nitroglycerin results in tolerance to its venodilating effects, whereas arteriolar action is maintained. This tolerance-induced shift in action from venous toward arteriolar dilation is normally masked by compensatory reflexes. PMID- 3091289 TI - Beneficial effect of aspirin in maintaining the patency of small-caliber prosthetic grafts after thrombolysis with urokinase or tissue-type plasminogen activator. AB - Despite successful thrombolysis of occluded prosthetic grafts, rethrombosis remains a problem. We investigated the efficacy of aspirin in maintaining patency of polytetrafluoroethylene grafts (3 mm X 3.5 cm) in canine femoral arteries after thrombolytic therapy. After induction of thrombosis, either tissue-type plasminogen activator (t-PA) or urokinase (UK) was infused just proximal to the thrombus (4000 U/min) until complete thrombolysis was achieved. Five of the 10 UK treated dogs and five of the 10 t-PA-treated dogs received aspirin immediately after recanalization, and aspirin was continued (325 mg/day) for 4 weeks or until occlusion occurred. A systemic aspirin effect was confirmed by marked depression of serum thromboxane B2 and absent platelet aggregation. Only two of the 10 grafts in the aspirin-free group remained patent for 4 weeks. The remaining eight grafts had all reoccluded by 2 weeks. None of the 10 grafts in the aspirin treated group reoccluded during the 4 weeks. This significantly improved patency (p less than .001) in the aspirin-treated group was observed equally in grafts treated with t-PA or UK. Thus aspirin is a potent agent in preventing rethrombosis after thrombolytic recanalization of prosthetic grafts. PMID- 3091288 TI - Thrombolysis with recombinant human tissue-type plasminogen activator in patients with peripheral artery and bypass graft occlusions. AB - Thirty-three patients with thrombosed peripheral arteries and bypass grafts, as confirmed by angiography, were treated with recombinant human tissue-type plasminogen activator (rt-PA). Twenty-six patients were treated with a dose of 0.1 mg/kg/hr and seven patients with 0.05 mg/kg/hr. Thrombus lysis and clinical improvement occurred in 22 of 26 (85%) patients in the 0.1 mg/kg/hr group. In seven of seven (100%) patients in the 0.05 mg/kg/hr group angiographic as well as clinical improvement were observed. Fifteen of the 33 patients required anticoagulation to maintain patency. Sixteen required secondary procedures to maintain patency. One (3%) patient required a blood transfusion for a hematoma at the catheter entry site. Three other patients developed small hematomas that were controlled without transfusion or intervention. Sixty-one percent of patients treated with the 0.01 mg/kg/hr dose and 86% of patients treated with the 0.05 mg/kg/hr dose maintained fibrinogen levels greater than 50% of their initial values. Infusion durations ranged from 1 to 6 hr (mean 3.9 hr). rt-PA appears to be a potent and selective thrombolytic agent that rapidly and safely lyses thrombi in peripheral arteries and occluded bypass grafts. PMID- 3091290 TI - CEDIA, a new homogeneous immunoassay system. AB - Genetic engineering of beta-galactosidase (EC 3.2.1.23) has led to the development of a new homogeneous assay system, CEDIA. The Z gene of the lac operon of Escherichia coli encodes a large enzymatically inactive polypeptide that spontaneously aggregates and folds to form active beta-galactosidase. Using recombinant DNA techniques, we have been able to engineer beta-galactosidase protein into a large polypeptide (an enzyme acceptor, EA) and a small polypeptide (an enzyme donor, ED). The EAs and EDs are both enzymatically inactive, but spontaneously associate to form enzymatically active tetramers. In the assay, hapten or analyte is attached to an ED, and an analyte-specific antibody is used to inhibit the spontaneous assembly of active enzyme. Analyte in a patient's serum competes with the analyte in the analyte-ED conjugate for antibody, modulating the amount of beta-galactosidase formed. The signal generated by enzyme substrates is directly proportional to the analyte concentrations in the patient's serum. We describe quick (5-15 min) colorimetric tests for digoxin, requiring no serum pretreatments or predilutions and suitable for use with centrifugal and random-access analyzers. PMID- 3091291 TI - A highly sensitive immunoenzymometric assay involving "common-capture" particles and membrane filtration. AB - This highly sensitive immunoenzymometric method involves monoclonal antibodies, a common-capture microsphere, and a rapid, membrane-filtration separation step. The common-capture solid phase is monoclonal anti-fluorescein antibody convalently attached to 6.5 micron-diameter latex particles. In sandwich-type assays for large-molecule analytes, the capture antibody is conjugated with fluorescein isothiocyanate and the probe antibody is conjugated with beta-galactosidase (EC 3.2.1.23). In competitive assays for small analytes, the analyte-beta galactosidase conjugate competes with the analyte in the clinical samples for the fluoresceinated capture antibody. After simultaneous incubation of the reagents for 2 h, the bound and unbound reagents are separated by filtration through the bottom of each well of a 96-well plate. Substrate (4-methylumbelliferyl-beta-D galactopyranoside) is then added to the wells, and the rate of product formation is determined kinetically for 12 min. The rate is proportional to the concentration of analyte in the sandwich assays and inversely proportional in the competitive assays. The assay results for choriogonadotropin, thyrotropin, digoxin, and thyroxin show the assay to be sensitive, rapid, and applicable to any size analyte. With this system, several different sandwich and (or) competitive-type assays can be performed simultaneously on the same plate. PMID- 3091292 TI - Discriminative ability of tests for free and total thyroid hormones in diagnosing thyroid disease. AB - We assessed the sensitivity, specificity, predictive value of a positive result, and efficiency of tests for total thyroxin, free thyroxin index, free thyroxin, total triiodothyronine, free triiodothyronine index, and free triiodothyronine in serum from 1619 consecutive new patients with suspected thyroid dysfunction. Multivariate discriminant analysis was also used. Free thyroxin index and free thyroxin were clearly the most sensitive indicators of hypothyroidism. In contrast, all of these tests identified hyperthyroidism with similar efficiencies. By stepwise discriminant analysis, the free thyroxin index was the most efficient test for distinguishing between euthyroidism and hyperthyroidism and between euthyroidism and hypothyroidism. The combination of tests for total thyroxin, free thyroxin index, triiodothyronine, and free triiodothyronine was optimal for separating euthyroidism, hyperthyroidism, and hypothyroidism. We conclude that the free thyroxin index, despite the introduction of newer technologies, is still the best thyroid hormone test for screening for thyroid disease. PMID- 3091294 TI - An improved approach to thyroid function testing in patients with non-thyroidal illness. AB - We have compared the results of serum thyrotrophin (TSH) measurements using a sensitive immunoradiometric assay (IRMA) with those of conventional thyroid function tests in 299 hospital inpatients with a range of non-thyroidal illnesses. Levels of total thyroxine (T4), free T4, total tri-iodothyronine (T3) and free T3 in the hypothyroid range were recorded in 8%, 15%, 19% and 49% of patients, respectively, whereas TSH (IRMA) was abnormally low in 1%. Furthermore, basal TSH (IRMA) accurately predicted the result of the thyrotrophin-releasing hormone test in 72 of the 74 patients in whom this test was performed and, unlike thyroid hormone measurement, identified patients with subclinical thyroid disease. It would appear that a single basal TSH (IRMA) measurement is the most appropriate screening test for thyroid dysfunction in patients with concomitant acute or chronic illness. PMID- 3091293 TI - Excretion of octopamine metabolites in neuroblastoma. AB - The urinary concentrations of o-hydroxymandelic acid, m-hydroxymandelic acid, p hydroxymandelic acid, homovanillic acid and vanillylmandelic acid were determined in 57 healthy children and 9 patients with neuroblastoma. The concentrations of o hydroxymandelic acid and p-hydroxymandelic were not significantly different for both groups whereas the concentrations of m-hydroxymandelic acid, homovanillic acid and vanillylmandelic acid were elevated 20- to 30-fold in the neuroblastoma patients. PMID- 3091295 TI - Adult onset stuttering and seizures. AB - A case is presented in which adult onset stuttering and focal seizures appear to be linked. The EEG showed left anterior and mid-temporal sharp waves. The patient responded well to combined therapy with phenytoin, fluency exercises, and stress reduction. The association between stuttering and seizures in adults and children, as well as treatment with anticonvulsants, are discussed. PMID- 3091296 TI - Human pancreatic growth hormone releasing hormone fails to stimulate human growth hormone both in Cushing's disease and in Cushing's syndrome due to adrenocortical adenoma. AB - An absent or severely blunted hGH response to an i.v. bolus injection (100 micrograms) of human pancreatic growth hormone releasing hormone (hpGRF 1-44) was found in seven female patients with Cushing's syndrome (five with pituitary dependent Cushing's disease and two due to an adrenal adenoma) and four men with pituitary dependent Cushing's disease. Three of the female and three of the male patients had an adequate hypoglycaemia after insulin administration. All these patients showed an absent or blunted hGH response after insulin induced hypoglycaemia. The GHRH data in these patients are in agreement with those in older literature on hGH responsiveness to stimuli such as L-dopa, arginine and insulin induced hypoglycaemia. It is concluded that hypercortisolism inhibits hGH release to various stimuli at the pituitary level. PMID- 3091297 TI - The preoperative and postoperative investigation of TSH and prolactin release in the management of patients with hyperprolactinaemia due to prolactinomas and nonfunctional pituitary tumours: relationship to adenoma size at surgery. AB - We report here our results of the pre- and post-operative assessment of prolactin and TSH status in 41 hyperprolactinaemic patients who underwent pituitary surgery over a 5 year period. Preoperatively in patients with prolactinomas (n = 33) the TSH response to domperidone decreased with increasing adenoma size. When the data are expressed on a group mean basis the exaggerated TSH response to domperidone in preoperative prolactinoma patients was reduced significantly in patients rendered normoprolactinaemic by surgery but persisted in those who remained hyperprolactinaemic. Similarly the reduced preoperative PRL responses to domperidone and TRH were significantly increased by successful surgery. In contrast patients with stalk-compression hyperprolactinaemia (n = 6) due to larger lesions which were not prolactinomas all showed reduced or absent TSH responses to domperidone. The PRL responses to domperidone and TRH were reduced or absent both in patients with prolactinomas and in those with stalk-compression hyperprolactinaemia. All patients with stalk-compression hyperprolactinaemia showed a delayed pattern of TSH response to TRH with 60 min values being greater than 20 min ones. In contrast a normal pattern of TSH response to TRH was observed in all patients with hyperprolactinaemia due to prolactinomas. Postoperatively TSH and PRL responses were largely unchanged in patients with stalk-compression hyperprolactinaemia regardless of whether normoprolactinaemia was restored by surgery. In conclusion a reduced or absent PRL response to TRH or domperidone is not diagnostic of the presence of a prolactinoma since it occurs in hyperprolactinaemic patients with prolactinomas or stalk-compression. In contrast, the TSH response to acute dopamine antagonism is exaggerated in most patients with small prolactinomas but not in those with stalk-compression hyperprolactinaemia and we have found this to be helpful diagnostically since the presence of an exaggerated TSH response to dopamine antagonism is evidence against the presence of stalk-compression hyperprolactinaemia. The observation of a delayed TSH response to TRH in a hyperprolactinaemic patient should alert the clinician to the possibility of stalk-compression hyperprolactinaemia due to a large lesion which may not be a prolactinoma. PMID- 3091298 TI - Cryptophthalmos--syndactyly syndrome without cryptophthalmos. AB - Based on a personal observation and a review of the literature five cases with the so-called cryptophthalmos-syndactyly syndrome but without cryptophthalmos are presented. It appears that eye lesions are non-obligatory components of a pleomorphic condition which may be overlooked in the absence of the name-giving anomaly. The diagnosis of the cryptophthalmos-syndactyly syndrome must be considered in patients with a combination of acrofacial and urogenital malformations with or without cryptophthalmos. PMID- 3091299 TI - Humoral immune response in tuberculosis: initial characterization by immunoprecipitation of 125iodine labelled antigens and sodium dodecyl sulfate polyacrylamide gel electrophoresis. AB - 125Iodine-labelled Mycobacterium tuberculosis antigens were immunoprecipitated with tuberculosis patients' sera and analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. A group of four polypeptide antigens of 55, 38, 28 and 18 kD were thus identified. The 38 and 28 kD polypeptides were the major antigens. Antibody response differed from one patient to another, both with respect to the number and quantity of antigens precipitated. Untreated patients and those undergoing treatment with antimycobacterial drugs also showed marked differences in their antibody response. Generally, immunoprecipitates from treated patients showed a larger number of antigen bands and the relative intensities of the bands was also greater. No correlation was observed between the immunoprecipitation profile and antibody titres determined by enzyme linked immunosorbent assay. PMID- 3091300 TI - Cell-mediated immunity to hepatitis B virus antigens in mice: correlation of in vivo and in vitro assays. AB - Cell mediated immunity (CMI) to hepatitis B viral antigens was studied in BALB/mice after immunization with purified hepatitis B surface antigen (HBsAg), or core antigen (HBcAg), with adjuvants. The two in vitro assays for cell mediated immunity (CMI), utilizing lymph node cells, were release of interferon after exposure to antigen, and blast transformation of lymphocytes, and the in vivo assay was ear swelling at 24 h after local injection of antigen. Immunization with HBsAg or HBcAg with adjuvants induced antigen-specific cutaneous reactivity; if no adjuvants were given, immunization with HBcAg, but not HBsAg, induced cutaneous reactivity. CMI could be adoptively transferred by lymph node cells, but for only a limited period after immunization with HbsAg or HBcAg. The ability of lymph node cells from mice immunized with HBV antigens to transfer adoptively CMI correlated well with their production of interferon after challenge with antigen in vitro, but less well with blastogenesis after challenge with antigen in vitro, or with cutaneous reactivity to antigen in the donor mouse. Reliable antigen-specific lymphokine release assays, rather than blast transformation of lymphocytes or cutaneous reactivity after antigen challenge, are required to assess CMI to HBV antigens in the mouse and, by inference, in man. PMID- 3091301 TI - Modulation of gingival Langerhans cell T6 antigen expression in vitro by interleukin 1 and an interleukin 1 inhibitor. AB - A human gingival organ culture system was used to test the hypothesis that interleukin 1 (IL-1) modulates the expression of the cortical thymocyte antigen T6 on Langerhans cells (LC). In cultures enriched with E. coli lipopolysaccharide, T6 expression peaked concurrently with supernatant IL-1 activity. Addition of exogenous IL-1 produced a dose dependent increase in LC T6 expression while not affecting the expression of the Class II antigens DR and DQ by LC. An IL-1 suppressor factor (ILS) was associated with the loss of T6 antigens which occurred in conventional organ cultures. ILS inhibited the thymocyte response to IL-1 and neutralized the effects of IL-1 on both thymocytes and LC. In isolation ILS depressed T6 expression by eliminating resting DR negative LC. This factor may act to regulative negatively, the action of IL-1 as has been suggested for IL-1 inhibitors of similar molecular weight. PMID- 3091302 TI - Cells reacting with the monoclonal anti-IL-2 receptor antibody AMT-13 in the regenerating thymus of irradiated mice. AB - The proportion and anatomical localization in murine thymus of T cell subpopulations, including those which are defined by the monoclonal anti interleukin 2 (anti-IL-2) receptor antibody AMT-13, were studied by flow cytofluorometry and by immunohistochemical methods, both in irradiated and in normal mice. As a consequence of irradiation the proportion of AMT-13 positive cells and that of Lyt-1 positive cells were markedly enhanced, while the proportion of Lyt-2 positive cells was reduced. The vast majority of the AMT-13 positive cells both in normal and in irradiated thymi were located in the subcapsular area of the thymic cortex, whereas the irradiation resistant Lyt-1 positive cells were located in the medulla. These findings are compatible with the view that, similar to the developing thymus in the mouse embryo, in the regenerating adult thymus, AMT-13+ cells include the activated pro-thymocytes that repopulate the irradiated thymus. PMID- 3091303 TI - Cultured human thymus epithelial monolayer cells induce CD4 expression on mononuclear cells of AIDS patients in vitro. AB - We investigated the in vitro effect of cultured human thymic epithelial monolayer cells on mononuclear cells (MNC) from patients with Acquired Immune Deficiency Syndrome (AIDS) and AIDS-related complex (ARC). Patients having undergone bone marrow transplantation (BMT), who showed a similar deficiency of T-lymphocytes expressing CD4 (Leu-3, T4), and healthy blood donors served as controls. Most epithelial monolayer cells were of thymic medulla origin, as documented using a panel of monoclonal antibodies to thymic epithelial cells. In AIDS/ARC patients the CD4-positive cells (ranging between 4 and 30% of MNC) increased by a factor of 1.56 (s.e.m. 0.15, n = 12) during a 2 h incubation on the monolayer. Human fetal lung fibroblasts were inactive in this respect. There was no consistent change in cells expressing CD3 (Leu-4, T3), CD5 (Leu-1) or CD8 (Leu-2, T8). In BMT patients and healthy controls, neither thymus epithelium nor fibroblasts had any effect on T cell marker expression. Incorporation of tritiated thymidine by stimulated or unstimulated lymphocytes was increased after incubation for 3 days on either epithelium or fibroblasts. We conclude that CD4 expression is induced on MNC from AIDS/ARC patients during a 2 h incubation on epithelial monolayers. PMID- 3091304 TI - Reduced number of natural killer cells in patients with pathological hyperprolactinemia. AB - Human natural killer (NK) cell activity, as measured against K-562 target cells, was evaluated in 23 untreated and in 11 bromocriptine-treated hyperprolactinemic female patients and in 63 age-matched healthy women using 51Cr-release assay. The NK cell activity was significantly reduced in untreated hyperprolactinemic patients with respect to that of normal subjects, but therapy with bromocriptine restored NK cell function of patients to the levels of normal controls. Moreover, a reduced number of Leu-7+ cells and of large granular lymphocytes in hyperprolactinemic patients, as compared to normal controls and bromocriptine treated subjects, correlated well with the decreased NK activity. Finally, 'in vitro' incubation with purified human prolactin, did not affect NK cell activity of blood mononuclear cells. The present results demonstrate that pathological hyperprolactinemia, in which a tuberoinfundibular dopaminergic defect has been postulated, is also associated with a reduction in NK cell number and function and indicate a possible interaction between prolactin, neuroendocrine system and NK cell lineage in man. PMID- 3091306 TI - Defects in cell-mediated immunity. AB - Defects in cell-mediated immunity result in remarkable susceptibility to opportunistic infection in contrast to the recurrent pyogenic infections observed in children with defects in antibody-mediated immunity. The major congenital defects in T lymphocytes are presented. PMID- 3091305 TI - Immunoglobulin- and J chain-producing cells associated with lymphoid follicles in the human appendix, colon and ileum, including Peyer's patches. AB - Immunohistochemistry of B cells associated with normal human Peyer's patches and solitary lymphoid follicles of the ileum, colon and appendix mucosa showed that local accumulation of IgG-producing cells is a common feature of gut-associated lymphoid tissue (GALT). These immunocytes have strikingly down-regulated J-chain expression, indicating that they belong to mature memory clones. They are located mainly in the dome areas, alongside the follicles, and to a lesser extent in the germinal centres, and are accompanied by a much smaller number of J-chain negative IgA- and IgM-producing cells. It is concluded that B cells of mature memory clones are retained in GALT, whereas relatively early counterparts with a high J chain-expressing potential probably emigrate rapidly after stimulation and seed distant secretory sites where they undergo terminal differentiation to produce mainly J chain-containing dimeric IgA. PMID- 3091307 TI - Oral cromolyn in food allergy: in vivo and in vitro effects. AB - The results obtained in vivo in a group of 24 patients treated with oral cromolyn and compared to a group of 10 patients treated with placebo are reported. All patients were affected by adverse clinical reactions (urticaria and/or angioedema) related to food ingestion. A significant reduction of signs and symptoms were observed after oral cromolyn therapy only in the patients affected by true food allergy (FA), i.e., IgE mediated reactions. No adverse reactions appeared in the treated patients. Because we found an enhancing effect exerted in vitro by cromolyn (SCG) on T-cell responsiveness in previous studies, in the present investigation we analyzed in more detail in vitro effects of SCG on T lymphocytes [i.e., phytohemagglutinin-induced interleukin-2 (IL-2) production] and IL-2 receptor expression on T cells. No significant effect was induced by SCG on IL-2 production, whereas IL-2 receptor expression on surface of T cells appeared significantly increased (P less than 0.001) by adding SCG in cultures. These clinical and immunological results are analyzed and discussed in relation to a possible in vivo effect(s) of cromolyn in allergic diseases. PMID- 3091309 TI - In vivo clearance of antibody-sensitized human drug carrier erythrocytes. AB - Antibody coating of resealed drug carrier erythrocytes may be useful for drug targeting to the reticuloendothelial system. We have investigated the survival in the circulation of anti-Rh antibody (IgG anti-D)-coated autologous erythrocytes loaded with gentamicin by hypoosmotic dialysis. Five subjects were injected with 15.2 +/- 0.4 ml and five additional subjects with 62.8 +/- 1.5 ml carrier cells. Survival of the cells was monitored by intraerythrocytic gentamicin concentration in blood. In the first subject group initial t1/2 was 0.21 +/- 0.06 hours and terminal t1/2 was 1.71 +/- 0.36 hours. In the second group initial t1/2 was 0.59 +/- 0.21 hours followed by a slow phase with a t1/2 of 89 +/- 28 hours. Results indicate that rapid drug delivery to the reticuloendothelial system by antibody sensitized carrier erythrocytes is possible, but small volumes of erythrocytes seem more efficient. PMID- 3091308 TI - Unusual presentation of a large infected hemophiliac pseudotumor in an autologous indium-111 WBC scan. AB - A false-negative In-111 WBC scan was obtained in a case of a large, infected hemophiliac pseudotumor. Following aspiration of the abscess, a positive scan was seen, demonstrating that In-111 WBC imaging occasionally may be misleading as a diagnostic tool. PMID- 3091310 TI - Preservation of islet function and morphology after transplantation into high dose streptozotocin-diabetic rats. AB - Rats made diabetic with 0.15 g/kg streptozotocin showed a complete absence of islet B cells in their pancreases, even after 3-6 months of normoglycaemia. Glucagon- and somatostatin-containing cells were preserved. In these animals transplantation of 5,000 cultured fetal islets was required to restore normal blood glucose and intermediary metabolite profiles after a meal challenge, while 2,000 islets resulted in a marked metabolic disturbance. The larger number of islets produced comparable effects whether transplanted under the kidney capsule or into the splenic pulp. In either site, however, considerable proliferation of adipose tissue was found by 3-6 months. Transplanted islets were then demonstrated to retain the normal morphology with a central mass of insulin containing cells surrounded by a ring of A cells in which a few D cells were embedded. PMID- 3091311 TI - [Efficacy of therapy with triethylphosphine gold in a case of Felty's syndrome]. PMID- 3091312 TI - [Use of laser therapy associated with a lysine ketoprofen gel in various pathologies of orthopedic importance]. PMID- 3091313 TI - The cerebrospinal fluid proteins in multiple sclerosis. AB - A specific and reliable diagnostic test for MS does not currently exist. However, most patients afflicted with this disorder demonstrate both qualitative and quantitative changes in CSF proteins. An abnormal immunoglobulin fraction synthesized within the CNS is frequently found to be electrophoretically distinct from other proteins of the CSF and quantifiable according to different formulas. Although an etiologic antigen has not been implicated as yet, these findings provide compelling evidence to support an immunopathologic basis for MS. PMID- 3091314 TI - Alpha-heavy chain disease. AB - A review of alpha-heavy chain disease (AHCD) emphasizing its histopathology and associated lesions is presented. Unusual clinicopathologic presentations and modern concepts regarding histogenesis of AHCD in the light of recent immunohistochemical findings are discussed. Increasingly reported cases of Burkitt's (or Burkitt-type) lymphoma involving distal small intestine or the ileocecal region in children are noted. PMID- 3091315 TI - A microcomputer program for individualizing factor VIII dosage in hemophilia patients undergoing major surgery. AB - A pharmacokinetic program that allows individualization of Factor VIII dosage regiments in hemophilia patients undergoing major surgery is described. The program, which is designed for the IBM PC microcomputer and compatible machines, is based upon the one-compartment open model with instantaneous input. In the framework of such a pharmacokinetic model, it is assumed that the elimination of Factor VIII is faster during the early post-operative period and that it decreases progressively over the following days. Since Factor VIII half-life is dependent on the time elapsed since the operation (short half-life values during the early post-operative period, longer half-life values thereafter), the pharmacokinetic model is a nonlinear one. A first-order 'variation' rate constant is used to describe the prolongation of Factor VIII half-life from the initial value immediately after surgery to the final value achieved several days later. Individualized estimation of the patient's kinetic parameters (initial half-life, 'variation' rate constant and volume of distribution) is performed through the Bayesian method. Therefore, for such estimation the program exploits the Factor VIII plasma levels measured in the individual patient as well as the population pharmacokinetic data of Factor VIII. After estimating the individual's Bayesian parameters, the program predicts the dosage regimen that will elicit the desired time-course of Factor VIII plasma levels. If requested, the program is able to calculate the least-squares estimates for the parameters of the pharmacokinetic model and dosage prediction can also be made on the basis of such estimates. The least-squares estimates are useful for calculating population pharmacokinetic parameters according to the Standard Two-Stage method. Some examples of clinical use of the program are presented. PMID- 3091316 TI - A three-dimensional graphics system for the stereotactic placement of heavy-ion beams. AB - A beam placement system for the heavy ion radiation treatment of intracranial arteriovenous malformations (AVM) is discussed. Heavy ion Bragg peak beams are used due to the depth dose distributions. The user interface and design for this computer system is described within this paper. PMID- 3091317 TI - Salt and experimental hypertension: the influence of age. AB - In a series of experiments, age-dependent differences in the development of DOCA saline hypertension (HPT) were studied in the rat. Immature animals developed--in contrast to the adult ones--a more severe and self-sustaining HPT, associated with a more pronounced retention of fluid and a greater increase of renal collagen which was preceded by a more rapid decrease in renal renin content. It is suggested that changes in intrarenal haemodynamics due to the suppression of renal renin-angiotensin system play a role in the pathogenesis of hypertensive renal lesions which develop more readily in immature animals and are responsible for their more severe HPT. Similarly, monkeys exposed to increased salt intake from earliest stages of postnatal ontogeny are also more prone to develop salt hypertension more rapidly than the adult ones. The increased salt intake before sexual maturity may thus be considered as a risk factor for the development of hypertension also in man. PMID- 3091318 TI - Functional outcomes following medical intensive care. AB - This study describes the long-term functional outcomes of a medical and coronary care ICU population. Baseline and 1-yr follow-up data were collected prospectively from all 2213 patients admitted during a 2-yr period. Patients were stratified into three groups based on their preadmission functional status: active (n = 917), sedentary (n = 1017), or severely limited (n = 279). Those with severe functional limitation before admission were twice as likely to undergo major interventions (p less than .005). This group also had a significantly (p less than .001) higher mortality and incurred significantly (p less than .01) higher hospital charges than the other two groups, even though hospital lengths of stay were similar. Finally, cumulative mortality was significantly (p less than .001) greater for the severely limited patients: 33% expired in the ICU, 42% died while still in the hospital, and 63% died after discharge. Most survivors regained their preadmission functional status, with 60% of the previously employed returning to work. However, even for hospital survivors, mortality was high and was related to prior functional status: active 7%, sedentary 20%, severely impaired 37%. PMID- 3091319 TI - Computer-controlled optimization of positive end-expiratory pressure. AB - Positive end-expiratory pressure (PEEP) is a standard treatment for patients with refractory hypoxemia due to an acute restrictive pathology. The therapeutic range of PEEP can be quite narrow. PEEP therapy has been optimized using invasive variables such as oxygen transport and pulmonary shunt, and noninvasive variables such as compliance; however, the measurements are complex. We constructed a computerized PEEP-optimization system consisting of a Siemens 900C ventilator, Siemens prototype sulfur hexafluoride analyzer, Siemens 940 lung mechanics analyzer, and a DEC 11/23 microcomputer. The user may choose from three different noninvasive PEEP titration algorithms: maximizing static total respiratory system compliance (CTR), maximizing functional residual capacity(FRC)-based compliance (CFRC), and normalizing FRC. The device was tested in six dogs with pulmonary injury induced by oleic acid. The system was constrained to 3-cm H2O PEEP steps at 20-min intervals. The algorithm normalizing FRC reached optimal PEEP levels in 40 min, with a mean difference from the desired FRC of 15 +/- 48 (SEM) ml. This corresponds to a mean percent error of 1.0% +/- 2.63%. The CFRC and CTR algorithms reached optimal PEEP levels in 60 and 40 min, respectively, and maintained a maximal compliance for 85% of the time. This system provides fully automated noninvasive PEEP titration and is flexible enough to incorporate easily any other PEEP titration algorithms. It should improve patient care by guaranteeing that PEEP therapy is truly optimized throughout the patient's recovery. PMID- 3091320 TI - Validation of a compact system for measuring gas exchange. AB - Measuring gas exchange in critically ill patients can provide valuable information on their nutritional status and energy expenditure. Several semiautomated machines are available for measuring oxygen consumption (VO2) and carbon dioxide production (VCO2). This study evaluated, under controlled laboratory conditions, a Gould 9000 IV prototype designed for use with mechanically ventilated patients. Various VO2 and VCO2 values were simulated at different combinations of frequency, tidal volume, minute ventilation, and inspired oxygen fraction (FIO2). Variations in frequency, tidal volume, and minute ventilation had no significant effect on the measured VO2 and VCO2, but FIO2 had a dramatic effect on the accuracy of VO2. Errors in measured VO2 were 2.6%, 3.5%, 5.9%, and 16.9% at FIO2 values of 0.22, 0.40, 0.60, and 0.80, respectively. Addition of a dead space to the spirometer dump port (to prevent room-air contamination) corrected a larger error initially found. The accuracy of VCO2 was +/- 2.6%. PMID- 3091321 TI - Pretreatment hyperchloremia in diabetic ketoacidosis. PMID- 3091322 TI - Reduced susceptibility to lipid peroxidation in cold ischemic rabbit kidneys after addition of desferrioxamine, mannitol, or uric acid to the flush solution. AB - Rabbit kidneys were stored for 24 hr at 0 degree C after single passage arterial flush with 30 ml of cold isotonic 0.9% sodium chloride (saline) solution alone or saline to which was added 12, 30, or 60 mM desferrioxamine, 1 or 3 mM uric acid, or 100 mM mannitol. They were then subjected to in vitro biochemical assay for evidence of free radical damage immediately after storage. Results were compared to those obtained with fresh, unstored kidneys. Levels of Schiff base fluorescence, diene conjugates, and thiobarbituric acid-reactive material were each significantly elevated in kidneys stored for 24 hr after flush with saline alone. These levels were in turn each significantly reduced by the addition of 60 mM desferrioxamine, 3 mM uric acid, and 100 mM mannitol to the flush solution. Likewise, glutathione redox activity fell in those flushed with saline alone, presumably in line with increased lipid peroxidation, but was restored to control levels by inclusion of the three scavenging agents. PMID- 3091323 TI - Protein secretion in bacilli. PMID- 3091324 TI - Genetic studies on protein export in bacteria. PMID- 3091325 TI - Secretion cloning vectors for guiding the localization of proteins in vivo. PMID- 3091326 TI - Ionophore-induced cell shape changes in Xenopus early embryos. AB - Local application of the Ca++ ionophore A23187 to the intact lateral ectoderm of Xenopus early neurulae causes changes in the shapes of the cells; ectoderm cells lose their relatively flat surfaces and become rounded. Some of the affected cells form microvilli. Ionophore was found to induce cell shape changes in ectoderm in the presence of cytochalasin-B, suggesting that microfilaments are not involved. Ionophore was also found to induce cell shape changes in neurula ectoderm when it was applied to embryos cultured in Ca++- and Mg++-free medium containing EDTA, suggesting that extracellular Ca++ is not utilized in the ionophore-induced cell shape changes. Similarly, the Ca++ antagonists D-600, which reduces the entry of Ca++ into cells, and TMB-8, which antagonises certain intracellular Ca++-dependent functions, did not inhibit the effects of A23187 on amphibian embryos. PMID- 3091327 TI - Chelating drugs and zinc. AB - Essential trace metals participate in a wide range of biochemical processes. Administration of drugs containing nucleophilic atoms, primarily N-, O- and S ligands, may result in formation of organometallic non-ionic complexes or chelates. The stability of the complex depends on the position of the metal in the first transition series, except for Cu2+, which forms stronger bindings than Zn2+ does. In nature, a wide range of chelates occur, e.g. as vitamin-metal complexes (Zn-thiamine, Zn-pyridoxamine and Zn-biotin). Phytate in unleavened grains forms unsoluble Zn-complexes. In the body, complex-formation is essential for the transport of Zn with circulating plasma albumin. Some examples of chelating drugs are given. Zn-pyrithione is used for local treatment of dandruff and pityrosporum folliculitis. Ethambutol is a strong metal-binding drug used for tuberculosis therapy. The mechanism of action is possibly related to inactivation of Zn and Cu in the pathogenic organisms. 8-hydroxyquinolines enhance Zn absorption, which is the reason for the successful treatment of acrodermatitis enteropathica. Effects of D-penicillamine, phenytoin, tetracycline and disulfiram on Zn metabolism are discussed. PMID- 3091328 TI - Slow response to treatment of acute bronchial asthma. PMID- 3091329 TI - [Long-term intubation following tracheotomy]. AB - Between 1981 and 1983 tracheotomy was performed on 61 patients in the Surgical University Clinic of Tubingen. The dominant factors in indication of tracheotomy was for 49% of patients the persistingly necessary artificial respiration, for 26% a better bronchial toilet and other reasons for 25%. With 40.5% of all cases pneumonia was the most frequent complication encountered with our patients. The most frequent bacteria was Pseudomonas aeruginosa. Because of the decisive advantage constituted by the possibility of unproved bronchial toilet an earlier realisation of tracheotomy is to be recommended. PMID- 3091330 TI - [The etiology of chronic diarrhea--an analysis of 433 cases]. PMID- 3091331 TI - [Metabolic effect of a amino acid solution in post-operative patients]. PMID- 3091332 TI - [An evaluation on the effect of nebulized sodium cromproxate (SCP) in artemisia pollen induced asthma]. PMID- 3091333 TI - [Immunologic diagnosis of tuberculous meningitis]. PMID- 3091334 TI - [Preliminary observation on the detection of tubercle antibodies in the micro serum of auricular lobulus by ELISA]. PMID- 3091337 TI - Computers--don't leave your staff behind. PMID- 3091335 TI - Assessment of impact of Medicare Prospective Payment System on care of persons with diabetes mellitus. AB - Professional review organizations (PROs) have been reviewing hospital admissions on diagnosis-related groups (DRGs) 294 and 295 (uncomplicated diabetes mellitus) at the direction of the Health Care Financing Administration (HCFA) to control inappropriate hospital admissions. Because of the possibility of an adverse effect from this policy on the quality of medical care for people with diabetes, letters were sent and/or telephone calls were made to each PRO to request information on denials of admissions or of reimbursement for the hospitalization of patients with diabetes. The answers revealed variations in PRO review procedures, little attention to quality of care, and an apparently inadequate data retrieval system. These inadequacies of the Medicare Prospective Payment System (PPS), which currently obscure its impact on the quality of the hospital care of diabetic patients, can be remedied. PMID- 3091336 TI - Arachidonic acid metabolite regulation of insulin secretion. PMID- 3091338 TI - Can you handle problem patients? PMID- 3091339 TI - Your office through the looking-glass. PMID- 3091340 TI - Protect yourself--a legal check list. PMID- 3091341 TI - Stress--survive on your terms. PMID- 3091342 TI - Acid-base balance affects electroretinogram b- and c-wave differentially in the perfused cat eye. AB - The pH concentration strongly affects b- and c-waves of the vitreal direct coupled electroretinogram (DC/ERG) in the arterially perfused cat eye, in which acid-base balance can be changed temporarily excluding extraocular regulation (Niemeyer and Steinberg, 1984; Dawis et al., 1984, 1985; Niemeyer et al., 1984;. To increase pHi we injected NaOH and NH4Cl or substituted for control perfusate low PCO2, low HCO3- perfusate. This induced an increase in b-wave and a decrease in c-wave amplitude. To decrease pHi we injected HCl and NaHCO3-, increased PCO2, or substituted high PCO2, high HCO3- perfusate. This induced a decrease in b-wave and an increase in c-wave amplitude. Covariation between standing potential and c wave was found in only three of the seven experimental conditions. The change in standing potential was faster than that in the ERG waves. It is suggested that changes in pH affect primarily the retinal component of the c-wave. The b-wave consistently followed the direction of the expected change in pHi. All effects were reversible. PMID- 3091343 TI - Effect of CS-514, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on lipoprotein and apolipoprotein in plasma of hypercholesterolemic diabetics. AB - CS-514, one of the derivatives of ML-236B which is an inhibitor of endogenous cholesterol synthesis, has been previously shown to effectively reduce low density lipoprotein (LDL) cholesterol in dogs, rabbits and humans. We determined the effect of CS-514 on glucose, lipid, lipoprotein and apolipoprotein (apo) levels in plasma of 8 hypercholesterolemic diabetics (2 males). Total and LDL cholesterol and apo B levels were significantly decreased (P less than 0.005) 3 months after CS-514 treatment. High density lipoprotein (HDL) cholesterol was increased (P less than 0.05). Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) did not change throughout the observation period. No clinically serious adverse effects were experienced by the patients. We conclude that CS-514 can be a useful drug in the treatment of hypercholesterolemic diabetics and is remarkably free of any evidence of toxicity or unwanted side effects even in diabetics. PMID- 3091344 TI - Rational design of substrate analogues targeted to selectively inhibit replication-specific DNA polymerases. AB - The authors' approach to the design of DNA polymerase-specific inhibitors, an approach based on the mechanism of action of 6-(p-hydroxyphenylazo)uracil, has been to disguise nucleic acid bases to mimic the purine substrates dGTP and dATP. Specifically, the strategy has been to synthesize bases with substituents that endow them with the capacity: to seek and react with unique features of the active site of a polymerase; and to form H bonds with complementary template pyrimidines apposing the active site. This strategy has yielded a series of novel, enzyme-specific dATP and dGTP analogues which are non-polymerizable and which inhibit their target polymerase by sequestering it to a complementary pyrimidine residue in primer:template. The work has involved primarily two replication-specific polymerases, B. subtilis DNA polymerase III (pol III) and mammalian DNA polymerase alpha (pol alpha). The initial design exploited the pyrimidine nucleus and produced inhibitors with Ki values in the micromolar range. Principles established with the pyrimidine derivatives have led to the development of bona fide purine nucleotide analogues which act as DNA polymerase inhibitors of high selectivity and unprecedented potency. For example, BuPdGTP, the 2'-deoxyribonucleoside 5'-triphosphate of N2-(p-n-butylphenyl)guanine (BuPG), lacks discernible activity against mammalian polymerases beta and gamma, whereas it inhibits mammalian pol alpha with a Ki of less than 10 nanomolar. Currently, the authors are exploiting BuPdGTP, BuPdGDP, and similar butylanilino derivatives of dATP to probe the active site of pol alpha and to develop other N2-substituted analogues which can bind selectively to the substrate sites of other important polymerases and nucleotide binding proteins. PMID- 3091345 TI - The pharmacologic management of the syndrome of inappropriate secretion of antidiuretic hormone. AB - There have been numerous treatment modalities reported in the literature concerning the acute and chronic treatment of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Water restriction remains the mainstay of therapy. However, patient noncompliance for this regimen often makes additional treatment modalities necessary. In the long-term treatment of chronic SIADH, lithium, demeclocycline, loop diuretics, and urea are helpful, regardless of the origin of the SIADH. The use of lithium is not recommended due to the incidence of digestive, cardiac, thyroid, and central nervous system side effects, as well as the demonstrated superiority of demeclocycline. Urea and loop diuretics, although shown to be effective, have not been used clinically to the extent as demeclocyline, and are not free of adverse effects. Phenytoin is limited in its use to the treatment of SIADH secondary to abnormalities of the hypothalamic pituitary axis, and plays no role in the treatment of tumor-induced SIADH. Demeclocyline has been shown to be effective in all types of SIADH. The lack of comparative studies of long-term treatment regimens makes the selection of a regimen of choice difficult. At this point loop diuretics or demeclocycline appear to be the regimens of choice based primarily upon case reports and relatively small comparative study patient populations. Further comparative studies are needed in an attempt to identify the most efficacious regimen with the minimal incidence of adverse effects. PMID- 3091346 TI - Pseudomonas aeruginosa susceptibility in a university hospital: recognition and treatment. AB - Pseudomonas aeruginosa continues to be a leading cause of nosocomial bacteremia and other serious, often life-threatening infections. The incidence of P. aeruginosa infection appears to be increasing. The resilience of Pseudomonas in the hospital environment, its endogenous virulence factors, and its current level of resistance to antimicrobials make it a formidable pathogen, particularly in a compromised host. Despite the availability of several effective antipseudomonal antibiotics, infections caused by this pathogen are still associated with significant morbidity and mortality. Early recognition and prompt intervention with appropriate antimicrobial agents are vital to successful management. Combination therapy with an aminoglycoside and an extended-spectrum penicillin or cephalosporin is recommended in the initial management of suspected or documented P. aeruginosa infections. PMID- 3091347 TI - Costs and strategies for managing nosocomial urinary tract infections. AB - Four cost studies show that extra time spent in hospital because of nosocomial urinary tract infection ranged from 0.6 to 5.0 days. Extra hospital charges ranged from $146 to $558 with an average cost of about $355. Updated hospital costs project annual national costs of $1.8 billion. Strategies for managing nosocomial urinary tract infections are presented. PMID- 3091348 TI - Economic evaluation of pharmacologic therapy. AB - Cost-benefit and cost-effectiveness analyses are defined and described, particularly as they apply to evaluating costs in pharmacologic therapy. The cost benefit analysis (CBA) approach is used to compare dissimilar alternatives, whereas the cost-effectiveness (CEA) approach compares similar alternatives with similar objectives. A CBA, for instance, will demonstrate the economic effects of a program and can thus be used as a tool to compare the outcomes of several programs. A CEA, on the other hand, can help determine which of several alternatives is the least costly in achieving a stated objective. A CEA approach was used to examine results of clinical trials with cefoxitin or piperacillin in 86 patients undergoing intraabdominal surgery at two institutions. Results of multivariate analysis showed that patients who had received piperacillin had significantly shorter hospital stays (1.59 days) than those who had received cefoxitin. Based on national average hospital per diem rates, piperacillin patients were said to have saved $680 compared with patients treated with cefoxitin. Moreover, piperacillin was less expensive than cefoxitin. PMID- 3091350 TI - Enteral feeds for adults: an update. PMID- 3091349 TI - Legal implications of diagnosis-related groups. AB - The legal ramifications of diagnosis-related groups (DRGs) on the health-care system in general and on pharmacists in particular are undetermined. As pharmacists continue to play an increasing role in therapeutic decisions, their exposure to malpractice suits will continue to rise. Pharmacists' liability in medical malpractice actually began prior to the introduction of DRGs, with the adoption by many states of "generic substitute" laws. Situations that can lead to judgments against pharmacists are reviewed. The majority rule of joint and several liability is explained. The conclusion that "DRGs are not a legal defense" is underscored by a dramatic presentation of a hypothetical court case. PMID- 3091351 TI - [Autoantibody profile in collagen diseases. A clinical-serological study of 250 patients from Tuebingen clinics]. AB - Sera from 250 patients with connective tissue diseases were tested for antinuclear antibodies by immunofluorescence (IFL) and immunodiffusion. In patients with systemic lupus erythematosus (SLE, n = 49), progressive systemic sclerosis (PSS, n = 30) and Sjogren's syndrome (n = 20), IFL showed antinuclear antibodies with a frequency of 70 to 100%. Patients with localized scleroderma (n = 16) and discoid LE (n = 38) had antinuclear antibodies in 31 and 21% of cases, respectively. In patients with vasculitis (n = 32), fluorescent antinuclear antibodies were only rarely detected (0-6%). In the immunodiffusion LE-specific anti-Sm antibodies were demonstrated in 10%, anti-nRNP nRNP antibodies in 20%, and anti-Ro antibodies in 37% of patients with SLE. In Sjogren's syndrome, anti Ro antibodies were found in 45% and anti-La antibodies in 35% of patients. 57% of patients with PSS had the disease-specific anti-Scl-70 antibody, while only 19% had antinucleolar antibodies as detected by IFL. In patients with localized scleroderma, dermatomyositis (n = 6) or vasculitis, no precipitating antibodies were detectable. The demonstration by immunodiffusion of nuclear antibodies in patients with discoid LE could be connected with a transition to a systemic course of the disease. PMID- 3091352 TI - [Gamma interferon in psoriatic arthritis]. AB - Fifteen patients with confirmed psoriatic arthritis were treated with recombinant interferon-gamma (IFN-gamma) between October 1985 and February 1986. In ten patients a marked relief of joint pain was achieved within 28 days. Daily doses of less than 200 micrograms IFN-gamma did not have any effect on the skin lesions. Tolerance of the drug, given subcutaneously, was dose-dependent, no side effects occurred with dosages of less than 100 micrograms/d. PMID- 3091353 TI - [Renal failure after infusion of sugar substitutes]. PMID- 3091355 TI - Nutritional needs of an infant or child with a cleft lip or palate. PMID- 3091354 TI - Optimum management of asthma in pregnancy. AB - In pregnancy complicated by asthma, the greatest risk to the fetus is severe and uncontrolled bronchospasm resulting in hypoxia. For this reason, the priority in management of the pregnant asthmatic should be effective control of asthma symptoms with an appropriate amount of asthma medication to accomplish this goal. In general, the management of the pregnant asthmatic does not differ greatly from that of the non-pregnant asthmatic. Virtually none of the commonly used asthma medications are totally contraindicated in pregnancy if their use is justified by the severity of the asthma in pregnancy. These include optimising non pharmacological means of controlling symptoms, using the smallest doses of antiasthma drugs necessary to control symptoms, basing the decision to use a drug on its benefit-to-risk ratio, avoiding recently introduced drugs (for which safety in pregnancy has not been adequately established), and using the inhaled route in preference to the oral route of administration. Ideally any changes in management should be made before the anticipated pregnancy. Well-controlled asthma appears to pose little risk to either the pregnant mother or the fetus and a favourable outcome of the pregnancy should be anticipated. The patient's justifiable anxiety can often be alleviated by ensuring that she fully understands the objectives of her management and participates in it. PMID- 3091356 TI - Paternity testing: experience with limited resources in Nigeria. PMID- 3091357 TI - [A rare case of factor VIII-inhibitor formation]. PMID- 3091358 TI - [Dental surgery in immunosuppressed patients]. PMID- 3091359 TI - [Studies of brain stem function in infants with apnea syndrome using acoustically evoked brain stem potentials and heart rate variability]. AB - Twenty-four infants aged between 6 days and 7 months and 2 infants (16 m and 3 y) were subjects of combined brain-stem auditory evoked potential and heart rate variability measurements. Ten infants had a sleep apnea syndrome and one a Near miss sudden infant death syndrome; thirteen infants formed the control group. Seventeen of the twenty-six infants had normal, age-depended brain stem potentials. All infants of the apnea syndrome-group, which had no therapy, had increased I to V interpeak latencies outside of the one-sigma level, the six infants treated with aminophylline were within the normal range. Heart rate variability measurements revealed the following mean +/- standard deviation of the control group: 4.5% +/- 1.5%; of the apnea syndrome-group without therapy: 5.4% +/- 2.0%. PMID- 3091360 TI - [Regulation of respiration during sleep in congenital central sleep apnea]. AB - We report on 2 children aged 13 and 14 months with congenital central alveolar sleep apnea which showed depression of respiratory drive during sleep resulting from dysfunction of central chemoreceptors. Hypoventilation was found to be more severe during NREM sleep (minimum of alveolar ventilation in stages 3/4) than during REM sleep. During NREM sleep arousal responses to hypoxia proved to be an important factor in influencing the level of alveolar ventilation and in preventing fatal asphyxia. PMID- 3091361 TI - [Cross correlation functions of acoustic evoked brain stem potentials]. AB - A method for the analysis of brainstem acoustic evoked potentials (BAEP) is presented. The calculation of the normalized cross correlation function between BAEP recordings of the right and left side yields a quantitative and objective valuation of the symmetry of the electrical brainstem activity. Contrary to the usual interpretation of latencies and amplitudes the BAEP waveform is also considered. To demonstrate the regular properties of the normalized cross correlation function 20 healthy subjects were tested. Different stimulus and recording conditions, the influence of the BAEP signal length on which the calculation of the cross correlation function is based as well as filtering of the BAEP with varying cutoff frequencies are studied. PMID- 3091363 TI - [German EEG Society. Part 1. 30th annual meeting. Munich, 10-12 October 1985. Abstracts]. PMID- 3091362 TI - [Electrophysiologic findings in lacunar infarcts]. AB - Lacunar lesions are small infarctions in the territory of small penetrating arteries of the brain. Because of their small size these lesions can only in part be detected by CT. Clinical symptoms do not always correspond with the lesions visible in the CT. We studied the somatosensory evoked potentials (SEP), the visual evoked potentials (VEP) and the electrically elicited blink reflex in 50 patients with lacunes to determine if there are any other lesions which are not detectable by clinical examination or CT alone. While VEP and the blink reflex showed pathological results in only a few of these patients the SEP were pathological in about 75%. The multiplicity of the lesions may be documented by means of these investigations. PMID- 3091365 TI - In vitro activity of carumonam (RO 17-2301) and twelve other antimicrobials against clinical isolates of Pseudomonas aeruginosa. AB - Minimal inhibitory concentrations of the monobactam carumonam (RO 17-2301) and twelve other antimicrobials were determined using agar dilution against 140 recent non-replicate clinical isolates of Pseudomonas aeruginosa. The most active drugs were ciprofloxacin, amikacin, imipenem and ceftazidime, inhibiting 96, 91, 90 and 86 percent of the strains, respectively, at or below the susceptibility threshold. The monobactams carumonam and aztreonam were active against 78 and 65 percent of the strains, respectively. Tobramycin inhibited 68 percent of the strains, and gentamicin and netilmicin 50 and 21 percent, respectively. Analysis of correlation coefficients revealed a low correlation between imipenem and the other beta-lactams and a remarkably good correlation between the beta-lactams (excepting imipenem) and the aminoglycosides. PMID- 3091364 TI - Heat shock and ecdysterone activation of the Drosophila melanogaster hsp23 gene; a sequence element implied in developmental regulation. AB - The regulation of the Drosophila melanogaster hsp23 gene by heat shock and ecdysterone has been analysed by measuring activities of hsp--Escherichia coli beta-galactosidase hybrid genes in transfected hormone-sensitive D. melanogaster cells. Mutation analysis identified multiple, distinct promoter elements. A sequence element, which also occurs in the promoters of several other developmentally regulated Drosophila genes, is present in regions of the hsp23 promoter that are essential for its ecdysterone, but not its heat-regulated activity; this element may represent a binding site for an ecdysterone--receptor complex. Mutant promoters that can be activated only by heat shock or by hormone have been constructed. Thus the two types of regulation of the hsp23 gene can function independently of each other. PMID- 3091366 TI - Hormonal regulation of the tricarboxylic acid cycle in the isolated perfused rat liver. AB - The effect of Ca2+-mobilizing hormones, vasopressin, angiotensin II and the alpha adrenergic agonist phenylephrine, on the metabolic flux through the tricarboxylic acid cycle was investigated in isolated perfused rat livers. All three Ca2+ mobilizing agonists stimulated 14CO2 production and gluconeogenesis in livers of 24-h-fasted rats perfused with [2-14C]pyruvate. Prazosin blocked the phenylephrine-elicited stimulation of 14CO2 and glucose production from [2 14C]pyruvate whereas the alpha 2-adrenergic agonist, BHT-933, did not affect the rates of 14CO2 and glucose production from [2-14C]pyruvate indicating that the phenylephrine-mediated response involved alpha 1-adrenergic receptors. Phenylephrine, vasopressin and angiotensin II stimulated 14CO2 production from [2 14C]acetate in livers derived from fed rats but not in livers of 24-h-fasted rats. In livers of 24-h-fasted rats, perfused with [2-14C]acetate, exogenously added pyruvate was required for an increase in the rate of 14CO2 production during phenylephrine infusion. This last observation suggests increased pyruvate carboxylation as one of the mechanisms involved in stimulation of tricarboxylic acid cycle activity by the Ca2+-mobilizing agonists, vasopressin, angiotensin II and phenylephrine. PMID- 3091367 TI - Natural selection versus primitive gene structure as determinant of codon usage. AB - Different codons are not utilized equally in known gene sequences. One of the important biases of codon usage is observed in the form of an enrichment of RNY codons, especially within RNN codon families. Such biases could represent the residue of a primitive repeating-RNY gene structure, or the outcome of natural selection, or both. Analyses based on the rates of silent substitutions, the frequencies of base doublets, and synonymous codon ratios for Escherichia coli, yeast, Drosophila and Xenopus proteins have been performed. The results rule out any significant support for a primitive repeating-RNY or repeating-RRY gene structure, and establish the important role of natural selection in determining the choice of codons. With strong intervention by natural selection, the relationship between primitive gene structure and codon usage necessarily becomes minimal. PMID- 3091368 TI - Cytosolic adenylates and adenosine release in perfused working heart. Comparison of whole tissue with cytosolic non-aqueous fractionation analyses. AB - Free cytosolic adenylates were examined in relation to adenosine plus inosine released from perfused working guinea-pig hearts. Whole-tissue adenylate data from freeze-clamped hearts were quantitatively compared with corresponding values obtained by subcellular fractionation of homogenized myocardium in non-aqueous media. Adenosine and inosine in venous cardiac effluents were measured by high performance liquid chromatography. Hearts, perfused at their natural flows, were subjected to various workloads, substrates and catecholamines to alter myocardial energy metabolism and respiration over a wide physiological range. Non-aqueous cytosolic ATP and creatine phosphate (CrP) accounted for more than 80% of the respective total myocardium content. The cytosolic CrP/Pi ratio was in near quantitative agreement with the overall tissue CrP/Pi ratio when the latter parameter was corrected for extracellular Pi. This was conclusive evidence that ATP, CrP and Pi were predominantly located in the cytosol of the well-oxygenated cardiomyocyte. Measured myocardial oxygen uptake (MVO2) was reciprocally related to the phosphorylation state of CrP [( CrP]/[Cr] X [Pi]) and hence that of ATP [( ATP]/[ADP] X [Pi]) assuming the creatine kinase at near-equilibrium at a near constant pH of 7.2. On the other hand, calculated mean free cytosolic ADP concentrations increased essentially linearly up to threefold with increasing MVO2 in the presence of virtually unchanged or only slightly decreased ATP levels; this was found both according to the whole tissue and the special subcellular fractionation data. Employing the myokinase mass-action ratio and substituting total cardiac ADP by the mean free cytosolic ADP concentrations, the mean free cytosolic AMP concentrations proved to be in the nanomolar range, i.e. up to three orders of magnitude lower than the overall tissue AMP content. We propose, therefore, that in the normoxic heart, AMP is located predominantly in the mitochondrial compartment. Nevertheless, both free cytosolic AMP concentration and release of adenosine plus inosine were apparently square or even higher-power functions of the rate of cardiac respiration. On the other hand, the mean purine nucleoside release seemed linearly correlated (r = 0.920) with the calculated free cytosolic AMP concentration. Our observations seem to suggest that the concentrations of free ADP and AMP in the cytosol are major determinants of the production of inosine and coronary vasodilator adenosine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3091369 TI - Structural analysis of poly(ADP-ribose)polymerase in higher and lower eukaryotes. AB - A phylogenetic survey for the poly(ADP-ribose)polymerase has been conducted by analyzing enzyme activity in various organisms and determining the structure of the catalytic peptides by renaturation of functional activities of the enzyme in situ after electrophoresis in denaturing conditions (activity gel). The enzyme is widely distributed in cells from all different classes of vertebrates, from arthropods, mollusks and plant cells but could not be detected in echinoderms, nematodes, platyhelminths, thallophytes (including yeast) and bacteria. The presence on activity gels of a catalytic peptide with Mr = 115,000-120,000 was demonstrated in vertebrates, arthropods and mollusks but no activity bands were recovered in many lower eukaryotes, in plant cells and bacteria. By using an immunological procedure that used an antiserum against homogeneous calf thymus poly(ADP-ribose) polymerase, common immunoreactive peptides were visualized in mammals, avians, reptiles, amphibians and fishes, while lacking in non-vertebrate organisms. Our results indicate that the structure of poly(ADP-ribose) polymerase is conserved down to the mollusks suggesting its important role for DNA metabolism of multicellular organisms. PMID- 3091370 TI - Crossed chemoprophylaxis assay between adriamycin and cis-platinum in recurrent superficial bladder tumor. AB - Of 146 patients with superficial bladder carcinoma, 66 (35 primary and 31 recurrent from failure of thiotepa chemoprophylaxis) relapsed following transurethral resection (TUR) and chemotherapy with adriamycin or cis-platinum. A new TUR was carried out. In case of progression in the number of tumors, size, stage or grade, treatment was begun with the other drug. If the tumor had the same characteristics, treatment was continued with the same drug. In both the primary and recurrent tumors with or without progression, cis-platinum controlled the tumor better than adriamycin, rescuing it from the latter and obtaining a recurrence index and disease-free interval as with cis-platinum alone. These results are more conclusive in primary tumors. PMID- 3091371 TI - Difluoromethylornithine and leukocyte interferon: a phase I study in cancer patients. AB - Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and human leukocyte interferon (IFN-alpha) have synergistic anti tumor activities in vivo in B 16 melanoma and in vitro against several human cancer cell lines. We have, therefore, carried out a phase I combination study with DFMO plus alpha interferon in the following manner: DFMO was maintained at a steady dose for the first four levels, 1.5 g/m2 every 6 hr. IFN-alpha was given in 100% increments ranging from 0.4 X 10(6)U/m2 to 3.2 X 10(6)U/m2 i.m. daily. At the fifth dose level both IFN-alpha and DFMO were raised by 100 and 50% respectively. From levels one through four the combination was well tolerated with no dose interruptions required because of G.I. toxicity or myelosuppression. However, at dose level 5, one-third of the patients required dose cessation and decrease due to nausea, vomiting and diarrhea. We conclude that for phase II studies the maximal tolerated dose is 3.2 million units of IFN-alpha/m2 and 1.5 g/m2 of DFMO every 6 hr. Of 12 patients with metastatic melanoma, 2 had partial remissions lasting 58+ and 36+ weeks. Two additional patients had minor responses lasting 29 and 32+ weeks. Minor responses were observed in a patient with colon carcinoma and a patient with renal carcinoma. The clinical activity of the combination is currently being pursued in a phase II study among patients with metastatic malignant melanoma. PMID- 3091372 TI - Acute effects of clometacin on renal prostaglandin biosynthesis in healthy subjects. AB - In 6 healthy subjects the effect of clometacin on renal function, sodium and water excretion, plasma renin activity and urinary excretion of prostaglandins has been studied. After four days of treatment with clometacin, the excretion of urinary prostaglandins E2, F2 alpha and 6 keto F1 alpha and thromboxane B2 were reduced by 61.2, 41.2, 59 and 42%, respectively. 62% reduction in plasma renin activity was also observed. There was no significant change in mean blood pressure, heart rate, body weight, creatinine clearance or urinary excretion of sodium. It is concluded that clometacin is an efficient cyclooxygenase inhibitor in healthy individuals with a normal sodium intake, and that caution is required when giving clometacin to patients at risk of developing renal failure during treatment with a cyclooxygenase inhibitor. PMID- 3091373 TI - Acceptance of antibiotic mixtures by infants and children. AB - The acceptance by children of two pharmacologically identical phenoxymethyl penicillin potassium and erythromycin ethylsuccinate mixtures, differing only in their flavouring agents, was compared in a randomised blind manner. The time a nurse required to give the drug to a child was recorded and a score of the acceptance was given by the nurse. The mean time to give erythromycin Brand 1 was 29 s (SD +/- 21, number of children = 20) and mean time to give Brand 2 it was 16 s (SD +/- 13, n = 18); the difference was significant (p less than 0.05). The mean scores were 2.9 (SD +/- 0.6) and 3.4 (SD +/- 0.5), difference -0.5 (p less than 0.025). The difference between the two penicillin products was not significant. The time required to give a medicine was a useful way to compare the effect of different flavouring mixtures on the acceptance of drugs by infants and children. PMID- 3091374 TI - B cell growth and differentiation induced by supernatants of transformed epithelial cell lines. AB - Growth and differentiation of B cells is thought to be regulated by soluble factors derived from T cells. However, human T cell lines and hybridomas have proved to be notoriously unreliable and unstable sources of such factors. We report here that three stable human bladder carcinoma cell lines T24, RT4 and 5637 produce, in a constitutive fashion, factors which promote growth and differentiation of human B cells. PMID- 3091375 TI - Antibodies reactive with the B1 molecule inhibit cell cycle progression but not activation of human B lymphocytes. AB - The B1 cell surface molecule (CD20) is a 35-kDa phosphoprotein expressed by B lineage cells during most stages of differentiation. Some monoclonal antibodies reactive with B1 induce activation while others, anti-B1a, inhibit B lymphocyte function. To further determine the requirement of B1 molecule function in proliferation and differentiation the effects of anti-B1a antibody binding on early cellular activation events were examined. Immunoglobulin secretion of lymphocyte cultures stimulated with pokeweed mitogen was maximally inhibited if the antibody (1-10 micrograms/ml) was added during the first 24 h of culture. However, even high antibody concentrations were unable to inhibit increases in free intracellular Ca2+ concentrations immediately following cross-linkage of cell surface immunoglobulin, or inhibit cell enlargement and the expression of transferrin and interleukin 2 receptors. Antibody binding to B1 inhibited RNA synthesis (37-80%) and progression through cell cycle following activation. In contrast, proliferation induced by phorbol myristate acetate was not inhibited by antibody binding to the B1 molecule. The findings that the earliest activation events and phorbol myristate acetate-induced proliferation were not inhibited by antibody binding to B1 suggest that inhibition is due to the blocking of a step of the activation process required for cell cycle progression and differentiation, rather than blocking initial signal transduction across the membrane or providing a negative or suppressive signal. PMID- 3091376 TI - Repertoire of murine lambda-positive variable domains: polyclonal induction of lambda isotypes and their associated pattern of antibody specificities. AB - The diversity of lambda variable (V lambda) domains is extremely restricted when compared to those of VH and V kappa. In addition, each V lambda domain is determined by the C lambda domain. For these reasons, the lambda system is an excellent model for the study of the associated VH region repertoire. The study of V lambda domain diversity has been limited by the small contribution (approximately 5%) of lambda-bearing proteins to the total Ig pool. We now show that treatment of BALB/c mice with rabbit anti-lambda 1 antibodies coupled to lipopolysaccharide induces a production of polyclonal lambda 1 light chain bearing Ig whereas, conversely, treatment with rabbit anti-lambda 2 antibodies induces a production of polyclonal lambda 2 + lambda 3 light chain-bearing Ig. The antigenic specificities of these two distinct lambda populations were then studied using B1355 dextran, (4-hydroxy-3-nitrophenyl)acetyl (NP) and 2,4 dinitrophenyl (DNP) as antigens. The anti-alpha(1-3)dextran antibody specificity was found to be mediated exclusively by antibodies bearing the lambda 1 isotype whereas the anti-NP and anti-DNP antibody specificities are mediated by both the lambda 1 and lambda 2 + lambda 3 isotypes. In addition, various mouse strains with the VHa or VHb allotypic haplotype and the rlo lambda 1 or r+ lambda 1 phenotype were treated with rabbit anti-lambda 1 antibodies. The lambda 1 anti-NP and anti-DNP antibody specificities were similar in all strains whereas the lambda 1 anti-alpha(1-3)dextran specificity was linked to the presence of the VHa allotypic haplotype. The mouse strains with the rlo lambda 1 or r+ lambda 1 phenotype did not differ in terms of their patterns of lambda 1 antibody specificities. PMID- 3091377 TI - Characterization of the role for calcium influx in mitogen-induced triggering of human T cells. Identification of calcium-dependent and calcium-independent signals. AB - Entry of Ca2+ into the cell is recognized as an important activation signal for mitogen-induced lymphocyte proliferation. Changes in free cytosolic Ca2+ [( Ca2+]i) can now be measured directly using the fluorescent reagent quin-2. To analyze the role of [Ca2+]i in human T cell activation, we have determined the effect of the calcium channel blocker, nifedipine, on phytohemagglutinin (PHA) induced lymphocyte proliferation. At a concentration of 50 microM, nifedipine is nontoxic, and prevents PHA-induced proliferation. In parallel the drug prevents the lectin-induced increase in concentration of [Ca2+]i and interleukin 2 (IL2) secretion; IL2 receptor expression is unaffected. In the presence of exogenous IL2, cell proliferation proceeds normally. Treatment of the cells with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate prevents the inhibitory effect of nifedipine on cell proliferation. Since TPA is itself nonmitogenic and does not affect levels of cytosolic Ca2+, these data and the data on IL2 receptor expression indicate that PHA can generate an activation signal(s) which is [Ca2+]i independent. PMID- 3091378 TI - The roles of interleukin 2 and interferon-gamma in human B cell activation, growth and differentiation. AB - The roles of interleukin 2 (IL 2) and interferon-gamma (IFN-gamma) in human peripheral blood B cell activation, growth and differentiation were examined. Highly purified B cells stimulated with Cowan I Staphylococcus aureus (SA) proliferated minimally and generated no immunoglobulin-secreting cells (ISC) without the addition of T cell supernatants (T sup) produced by mitogen-activated T cells. Recombinant IL 2 (rIL 2) alone was able to promote maximum proliferation and generation of ISC in cultures of highly purified SA-stimulated B cells when present from the initiation of the incubation. IFN-gamma, by contrast, could not support either response alone. When a two-step culture system was employed to determine the effect(s) of T cell influences during both initial activation and in propagating the response following activation, it was found that B cells activated by SA alone subsequently responded maximally to T sup but only minimally to IL 2 and not at all to IFN-gamma. However, the presence of T sup, rIL 2, or rIFN-gamma during initial activation with SA was found to facilitate greatly the subsequent capacity of the activated B cells to proliferate and differentiate in response to either T sup or IL 2. These data suggest two distinct pathways of human B cell responsiveness. Activities in T sup other than IL 2 or IFN-gamma can support the growth and differentiation of B cells initially activated with SA alone, whereas rIL 2 is capable of promoting these responses maximally only when B cells have been initially activated by SA in the presence of T cell lymphokines, such as IL 2 or IFN-gamma. The results emphasize the role of specific T cell factors in determining the outcome of humoral immune responses. PMID- 3091379 TI - Immunoglobulin heavy chain gene rearrangements in X-linked agammaglobulinemia. AB - X-linked agammaglobulinemia (XLA) appears to involve a defect in human B lymphocyte differentiation which is manifested at the pre-B cell stage. The defect segregates as an X-linked recessive trait but is not a single genetic entity. IgM-producing B cell clones were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells of patients with the XLA defect linked to the DXS3 and DXS17 chromosomal loci. Individual XLA B cell clones were demonstrated to have rearrangements of the JH regions of both immunoglobulin VH region loci. The rearranged JH regions of the B cell clone ALA 19 were molecularly cloned and their nucleotide sequence was determined. Both JH associated rearrangements (designated 191 and 192) resulted from the juxtaposition of variable (VH), diversity (D) and joining (JH) segments (VHDJH rearrangements). The 191 rearrangement employed a VH segment belonging to VH subgroup III and a JH4 segment. The 192 rearrangement employed a VHII and a JH6 segment. The D191 and D192 segments encompassed 21 and 28 nucleotides, respectively, and showed little homology to each other or to previously reported human D sequences. Surprisingly, both VHDJH complexes had open reading frames. However, in accord with principles of allelic exclusion, only the 191 allele was detectably expressed in the total RNA of the cell. A possible mechanism for the lack of expression of the 192 allele is discussed. We conclude that the DXS3 DXS17-linked XLA defect does not preclude VH to DJH rearrangements or the expression of VH containing heavy chain molecules. PMID- 3091381 TI - Differentiation antigens on rhesus monkey lymphocytes. II. Characterization of RhT3, a CD3-like antigen on T cells. AB - A monoclonal antibody FN18 is described, which is specific for mature rhesus monkey T lymphocytes. It defines a cell surface antigen, composed of two polypeptide chains with a molecular mass of 22 and 27 kDa. In view of these and other similarities with the human T3 or CD3 antigen, it was designated as RhT3. Expression, distribution and certain functions of RhT3 were compared with those of its human counterpart. Analogous to anti-CD3 antibodies in man, FN18 is able to modulate its target antigen, has mitogenic properties and is able to block the pokeweed mitogen and concanavalin A-driven cell proliferation, but not that caused by phytohemagglutinin. In spite of such minor dissimilarities the available data strongly suggest that the RhT3 antigen is the rhesus monkey's homologue of the human CD3 antigen. PMID- 3091380 TI - Suppression of specific IgM, IgA and IgG responses in mice treated with anti delta from birth. AB - In contrast to previous studies, we report that heterologous anti-delta antibodies can act as a powerful multi-class humoral immunosuppressant. Primary direct plaque-forming cell (IgM) responses of BALB/c mice injected from birth with a rabbit anti-delta antiserum were reduced to 3% of control levels against a T-dependent antigen (sheep red blood cells), and to 2% against a T-independent antigen (dextran); IgA responses against 2 intraduodenal injections of cholera toxin were reduced to 7% of control levels. Other secondary immune responses of anti-delta-suppressed mice were suppressed to a lesser degree. IgM plaque responses generated by 2 injections of sheep red cells, for example, were reduced to 50% of control levels, with reduction of the corresponding IgG response to 42%. The multi-class suppression observed indicates a clonal differentiation pathway in which the IgD+ cell develops into IgM-, IgA- and IgG-secreting cells. In light of reports that the IgD+ cell is antigen sensitive, our demonstration that IgD is capable of delivering the same sort of immunosuppressive signal in response to anti-heavy chain antibodies that IgM delivers also suggests, though it does not establish, an antigen-receptor role for IgD. PMID- 3091382 TI - A nonspecific disturbance of the gonadostat in women with transsexualism and isolated hypergonadotropism in the male-to-female disturbance of gender identity. AB - Principal parameters of gonadostat function were determined in 15 female-to-male (F-M) and 7 male-to-female (M-F) transsexual patients (T), all homosexuals. The data were compared with normal heterosexual controls of the respective sex. Anamnesis revealed prolongation of the menstrual cycles in F-M patients, mainly in those taking previously medication with depot-testosterone. However, also in patients with no previous medication the basal body temperature chart revealed anovulatory cycles (all 4 examined patients). In 8 of 9 patients (82.2%) with no previous medication an elevation of serum testosterone was found (63-600 ng/dl). No disturbances in gonadal functions were found in M-F group (semen analysis), serum testosterone was normal (328-710 ng/dl) except 1 case with reduced testosterone level (200 ng/ml). Both women and men with transsexualism revealed significantly higher mean basal serum concentration of LH in comparisons to controls (F-M: 23.14 +/- 16.16 vs 7.56 +/- 4.23; M-F 15.30 +/- 6.49 vs 5.75 +/- 3.66). No changes in basal serum FSH concentration were present. GnRH test (100 micrograms i.v.) revealed decreased evocability of LH in woman with T and exaggerated LH response in men with T. FSH hyperresponse to GnRH was nonsignificant in F-M and significant in M-F T. It is concluded that F-M transsexualism is associated with nonspecific disturbances of gonadostat since hypergonadotropism coexists with the signs of impaired gonadal function. In M-F T and isolated hypergonadotropism coexisted with specific, increased sensitivity of the pituitary to GnRH. PMID- 3091383 TI - Experimental analysis of the adhesion reaction between isolated Chlamydomonas flagella. AB - Protocols are presented for producing reproducible in vitro agglutination between Chlamydomonas flagella, based on previous studies by Kohle et al. The results indicate that the adhesive interactions occur between glutaraldehyde cross-linked flagella and can be cross-linked by glutaraldehyde. They are sensitive to divalent cations and, to a lesser extent, to monovalent ions, an inhibition that is fully reversed when the ions are removed. The ambiguities inherent in in vivo studies, particularly in a system where the adhesion molecules have been shown to be in a dynamic state of turnover and inactivation, are eliminated, and numerous studies involving enzyme digestion, antibodies, lectins and the like should now be possible with this adhesion system. PMID- 3091384 TI - Early nuclear events in lymphocyte proliferation. The role of DNA strand break repair and ADP ribosylation. AB - The previously reported extensive DNA strand breakage in resting murine splenic lymphocytes is not an artifact of the extraction or assay procedure. The benzamide inhibitors of poly(ADP ribose) synthetase (pADPRS), such as 5 methoxybenzamide (MBA), had been shown to block the strand break repair occurring within 2 h of activation of splenic lymphocytes by the mitogen concanavalin A (conA); the inhibitors also blocked early events in proliferation, such as blast formation, as well as entry into S phase. Inhibitors of pADPRS blocked lymphocyte proliferation by inhibiting the activity of this enzyme, rather than by non specific effects. Aphidicolin, an inhibitor of alpha-polymerase, also prevented DNA strand break repair in conA-stimulated cells but, unlike MBA, did not prevent blast formation. DNA strand breaks accumulated in the presence of MBA at the same linear rate (300-400/h) in both resting and conA-treated cells. We and others had hypothesized that this accumulation was due to a continuous production of strand breaks in lymphocytes, leading to their accumulation in presence of repair inhibitors. However, incubation of the cells with aphidicolin at concentrations that inhibited repair did not result in any increase in strand breaks. The hypothesis of continuous cycling of breaks is incorrect; accumulation of breaks was due to some indirect effect of MBA, such as a possible disinhibition of an ADP-ribosylation-sensitive endonuclease described in other cell types. All of the early stages of lymphocyte proliferation, including blast transformation (but not DNA synthesis) require ADP ribosylation. Repair of DNA strand breaks is not a precondition for blast formation, though experiments involving the combined effects of MBA and aphidicolin showed that repair of the breaks is essential in order for the cells to replicate their DNA. Our data are consistent with a model suggesting that DNA strand breaks introduced into differentiated cells act as an additional safety-catch mechanism that restrains them from replicating their genetic material but not from undergoing the early stages of proliferation. PMID- 3091385 TI - Selective inhibition of the proliferation of various murine hemopoietic progenitor cells by cholera toxin. AB - We have studied in detail the effects of cholera toxin (CT), its pentameric B chain subunit (toxoid) and the A-promoter chain on the differentiation of hemopoietic progenitor cells. Murine marrow cells were treated either with CT or its subunits. After stimulation with either the multilineage growth factor (multi CSF; also called interleukin 3 or HCGF) or other hemopoietic regulators (colony stimulating factors, or CSF), the clones grown in semisolid collagen cultures were scored in situ. Pluripotent stem cells (CFU-S) and multilineage (mixed CFU) or lineage-restricted progenitors (CFU-c) were estimated. We found that CT sensitivity is gradually gained by cells through the stepwise differentiation processes (i.e., CFU-S less than multilineage CFC less than committed CFC less than maturing cells). CT also has a selective, dose-dependent inhibitory effect (1 microM to 1 pM) on hemopoietic lineages (basophil-mast cells less than megakaryocytes less than neutrophils less than monomacrophages). These phenomena were obvious when the clonal growth was supported by multi-CSF but, interestingly, were not observed when lineage-restricted CSF were used. They furnished additional evidence that multi-CSF activates cells in a specific manner. This growth factor involved in progenitor cell self-renewal control may contribute to maintaining, on maturing cells, characteristics that are normally the attributes of progenitors. PMID- 3091386 TI - A role for the macrophage in normal hemopoiesis. II. Effect of varying physiological oxygen tensions on the release of hemopoietic growth factors from bone-marrow-derived macrophages in vitro. AB - The effect of oxygen tensions in the physiological range as an environmental signal on the growth of in vitro murine hemopoietic progenitor cells and the production of hemopoietic growth factors (HGF) from macrophages was investigated. Early (BFU-E) and late (CFU-E) erythroid and granulocyte-macrophage (GM-CFC) progenitor cells were cultured in an atmosphere containing 2%, 3.5%, or 5% oxygen. For both the BFU-E and CFU-E populations, a gas phase containing 3.5% oxygen proved to be optimal, producing greater colony numbers than cultures incubated under 2% or 5% oxygen-tension conditions. For GM-CFC growth, 2% and 3.5% oxygen resulted in a greater stimulation than 5% oxygen. Macrophages derived from unseparated and unstimulated mouse bone marrow cells were cultured on hydrophobic Teflon foils under varying oxygen-tension conditions. The production of erythropoietin (epo), present in the culture supernatants, increased as the oxygen concentration increased from 2% to 3.5%, but then decreased as the oxygen concentration was increased further, from 3.5% to 5%. The presence of a factor demonstrating functional similarity with Interleukin-3 was produced optimally under 5% oxygen-tension conditions. The production of granulocyte-macrophage colony-stimulating factor (GM-CSF) was not significantly affected by changing the oxygen-tension conditions. These results demonstrate that physiological oxygen tension plays an important role not only in the growth of hemopoietic progenitor cells, but also as a physiochemical signal that macrophages can sense and respond to in order to regulate the production of specific secretory products. PMID- 3091387 TI - Evidence for the role of leukotrienes C4 and D4 as essential intermediates in CSF stimulated human myeloid colony formation. AB - Products of the lipoxygenation of arachidonic acid have been shown to induce a variety of effects on cells of myeloid lineage. Colony-stimulating factor causes release of arachidonic acid from cell membranes, which then undergoes oxygenation via the cyclooxygenase and lipoxygenase pathways. Nordihydroguaiaretic acid (NDGA) and 3-amino-1-[m(trifluoromethyl)-phenyl]-2-pyrazoline (BW 755C), compounds that inhibit both the cyclooxygenase and lipoxygenase pathways, cause dose-dependent inhibition of CSF-induced human granulocyte-monocyte colony formation in vitro, with complete inhibition at 20 and 50 microM, respectively. Indomethacin, which inhibits cyclooxygenase but not lipoxygenase, has no effect on colony growth at 50 microM, which is well in excess of the dose needed for complete inhibition of cyclooxygenase. Leukotrienes (LTs) C4 and D4 (5-100 ng/ml) reverse NDGA inhibition of colony growth. At similar concentrations, neither leukotriene B4 or 5-HETE caused reversal of NDGA inhibition. These results support a role for LTC4 and LTD4 as essential intermediates in CSF-stimulated myeloid colony formation. PMID- 3091388 TI - Exercise-induced asthma. AB - All asthmatics have exercise-induced asthma (EIA). In periods where the asthma spontaneously deteriorate, there will be more exercise-induced asthma. About 3/4 of the asthmatics will have a positive exercise test on the first challenge. Exercise is not the best test to obtain the diagnosis of asthma, as other tests, e.g. inhalation of histamine, is more sensitive and specific. The best pretreatment of EIA is inhaled beta 2-agonists. Inhaled, nebulized SCG seem to offer better protection against EIA than inhalation of SCG as a powder and is most effective in children. EIA should today primarily be used in studies concerning the pathogenesis of asthma and in the evaluation of medication against asthma. PMID- 3091389 TI - Water loss from the respiratory tract during hyperventilation in normal subjects and in asthmatics. AB - Expiratory water loss was measured in four asthmatics and in four healthy subjects by leading the expired air through a tube filled with silicagel during hyperventilation. No difference in water loss was seen as the average water loss was 0.025 g/l for the asthmatics and 0.029 g/l for the healthy subjects. After hyperventilation PEF decreased more than 20% in the asthmatics while no change was seen in the lung function of the healthy subjects. It is concluded that expiratory water loss per se is not the reason for the decrease in lung function seen in asthmatics after exercise and hyperventilation. PMID- 3091390 TI - Isocapnic hyperventilation. AB - Eucapnic hyperventilation is probably the same expression of asthma as exercise induced asthma. Some dispute exists about the refractory period after the two challenges. Some claims that an refractory period exists after exercise-induced asthma and some cannot find any refractory period. The changes in the ventilatory capacity of asthmatics following exercise and eucapnic hyperventilation are similar. PMID- 3091391 TI - Schistosoma mansoni: nitrothiazolines and the male tegument. AB - Within 24 hr of treatment of the mouse host with BW484C, 2-[5-nitro-2 (pivaloylimino)-4-thiazoline-3-yl]diacetamide, pairs of Schistosoma mansoni exhibited "hepatic shift" and began to leave the mesenteric veins. The tegument of the males was altered, both morphologically and physiologically, while that of females was unaffected. This morphological damage to males correlated well with therapeutic efficacy against both sexes in a range of analogues of BW484C. However, parasites removed from mice after treatment but before the hepatic shift and then maintained in vitro were far from moribund as treated males could be maintained for 8 days in vitro, although this was 5 days less than males from untreated mice. Females survived as well as control worms. In contrast, male and female S. mansoni remaining in their host after therapy were invaded by host cells in the liver after 2 days. The morphological effects and reduction of the in vitro survival of males treated in the mouse and removed after 24 hr could be simulated by in vitro exposure for 24 hr to 10(-5) M BW484C. Females were not susceptible to this regime. It was concluded that worm pairs were swept to the liver as a result of drug dependent damage to the tegument of the male and that phagocytic invasion of male and female schistosomes by host cells within the liver was an important factor in the efficacy of BW484C. The biochemical events underlying the effects on the tegument of male worms remain unknown. PMID- 3091392 TI - Effect of epidermal growth factor on growth and maturation of fetal and neonatal rat small intestine in organ culture. AB - Small intestinal explants from pre- and post-natal rats were incubated in an organ culture system in the absence and presence of epidermal growth factor (EGF). The rate of synthesis of small intestinal DNA and protein as well as the activity of lactase and alkaline phosphatase increased rapidly between 17 and 20 day gestational age, whereafter they declined. The maximal incorporation of 3H thymidine and 14C-alanine into DNA and protein, respectively, was significantly stimulated by EGF (100 ng/ml). EGF had no effect on the activity of either lactase or alkaline phosphatase in the small intestinal explants. PMID- 3091393 TI - Delayed clearance from the murine uterus of gonococci enclosed in an artificial polysaccharide matrix. AB - The fate of Neisseria gonorrhoeae in the murine uterus and adjacent oviduct following an intrauterine inoculation was investigated. We compared also the rate of clearance of gonococci that were and that were not enclosed in an artificial polysaccharide matrix made of agar. Gonococci suspended in phosphate buffered saline were rapidly eliminated from the murine uterus and few viable cells were recovered 24 h after inoculation. The clearance of agar-enclosed gonococci was markedly delayed and viable cells were recovered 5 days after inoculation. Our data suggest that the presence of an artificial polysaccharide matrix around gonococci enable them to persist much longer in the murine genital tract. PMID- 3091394 TI - Evaluation of the cytotoxic activity of some alkaloids from Epinetrum delagoense Diels. I. PMID- 3091395 TI - Cytotoxic activity of some alkaloids from Epinetrum delagoense Diels: electron microscopy studies. II. PMID- 3091396 TI - [Assay of polychlorobiphenyls in human blood in relation to epidemiological studies]. PMID- 3091397 TI - Archaebacterial and eukaryotic ribosomal subunits can form active hybrid ribosomes. AB - Purified ribosomal subunits from the extremely thermoacidophilic archaebacterium Sulfolobus solfataricus are able to recognize ribosomal subunits from the yeast Saccharomyces cerevisiae forming hybrid monosomes that can be revealed by sucrose gradient analysis and are active in peptide bond formation. Both reciprocal combinations (archaebacterial 30 S + eukaryotic 60 S and archaebacterial 50 S + eukaryotic 40 S) are functional. In contrast, no hybrid couples are formed between subunits of yeast and Escherichia coli ribosomes. These results indicate that ribosomes of at least one archaebacterial species share specific structural features with those of the lower eukaryote S. cerevisiae. PMID- 3091398 TI - Chromosomal loop anchorage sites appear to be evolutionarily conserved. AB - We have previously identified a class of DNA sequence elements, termed matrix association regions (MARs), which specifically bind to nuclear matrices in vitro and are believed to be at the bases of chromosomal loops in vivo. Here we demonstrate that nuclear matrices prepared from the yeast Saccharomyces cerevisiae will specifically bind an MAR sequence derived from the mouse kappa light chain immunoglobulin gene. This suggests that both MAR sequences and their binding sites have been strongly evolutionarily conserved. PMID- 3091399 TI - Sequence analysis of phosphoserine-containing peptides. Modification for picomolar sensitivity. AB - Sequencing of phosphoserine-containing peptides yields normally no identifiable PTH-derivatives at those positions where phosphoserine is located. Here a new method is described which allows identification of the position of phosphoserine by chemical modification just before sequence analysis. In a one-step microbatch reaction, phosphoserine present in the intact peptide can be transformed quantitatively into stable derivatives such as beta-methylaminoalanine (MAA), S ethanolcysteine or S-ethylcysteine. These derivatives are detectable during microsequencing with less than 100 pmol peptide using an Applied Biosystems gas phase sequencer equipped with an on-line PTH amino acid analyzer. PMID- 3091400 TI - Porcine tissue plasminogen activator. Immunoaffinity purification, structural properties and glycosylation pattern. AB - Tissue plasminogen activator was purified in high yield from pig heart by immunoaffinity chromatography and characterized by analysis of the glycosylation pattern and the N-terminal amino acid sequence. Comparisons with the human enzyme reveals residue exchanges in the A-chain at positions 3 (porcine Arg/human Gln) and 5 (Thr/Ile), and in the B-chain at positions 6 (Tyr/Phe), 10 (Thr/Ala) and 20 (Val/Ala). The glycosylation pattern for the porcine activator was determined by endoglycosidase treatment followed by gel electrophoresis. The A-chain contains a single high-mannose type of N-linked glycan structure and the B-chain contains a complex type of oligosaccharide. A similar but not identical pattern has been observed for the human activator, purified from melanoma cells. PMID- 3091401 TI - Purification and characterization of recombinant murine immune interferon. AB - The recombinant murine immune interferon (rMu-IFN-gamma) was purified to homogeneity from Escherichia coli harboring the expression vector of murine IFN gamma. The purified rMu-IFN-gamma showed an Mr of 15 000 in SDS-polyacrylamide gel electrophoresis. Results of amino acid analysis, amino- and carboxyl-terminal analyses and peptide mapping of rMu-IFN-gamma suggest that it has the complete protein sequence predicted on the basis of cDNA except for lack of four amino acid residues from the mature carboxyl-terminus. PMID- 3091402 TI - Senescence-associated decrease of NADPH-induced lipid peroxidation in rat liver microsomes. AB - Senescence is associated with decrease in the NADPH-induced lipid peroxidation in liver homogenate as well as rough and smooth microsomes of female rats. In the microsomal fractions, sensitivity to NADPH-induced lipid peroxidation is high in young adults (3-month-old), decreases in middle aged (12-month-old) and reaches lowest levels in senescent (30-month-old) rats. Increasing the concentration of co-factors or time of incubation does not alter this resistance observed in the senescent rats. Major factors responsible for this resistance in senescent rats seem to be low levels of substrate in the c reductase, cytochrome P-450 and high cholesterol:phospholipid ratios besides enhanced levels of superoxide dismutase, alpha-tocopherol and reduced glutathione. PMID- 3091403 TI - Consequences of hunger for individuals and societies. AB - Famine and the manifestations of acute hunger that result are an unnecessary disgrace to our global society and serious in their political, economic, and social consequences. Probably more damaging is the chronic undernutrition that afflicts such a large proportion of the populations of developing countries and the hidden hungers of iron deficiency, avitaminosis A, and iodine deficiency disorders that are enormously widespread. Famine in the modern world is almost invariably superimposed on chronic undernutrition that is not solved with emergency relief. Adaptation to this undernutrition requires a reduction in physical activity needed for household and community improvement as well as work output. Iron deficiency interferes with cognitive performance, resistance to infection, and capacity for work. Other nutrient deficiencies add to the damage to the individual and society. Prevention of famine and hunger is not primarily a technological issue, but a moral, political, and social one. PMID- 3091404 TI - Benzidine: mechanisms of oxidative activation and mutagenesis. AB - Benzidine oxidative activation may proceed by peroxidase-catalyzed one-electron oxidation via free radical intermediates, or by N-acetylation followed by monooxygenase-catalyzed N-hydroxylation. The peroxidase route has been examined by using horseradish peroxidase or prostaglandin H synthase in vitro. In the presence of nucleophiles such as phenols, thiols, or nucleic acids, isolable adducts are formed. The structures of these adducts have been elucidated by spectroscopic methods. The Ames test provides a useful system for studying benzidine bioactivation to mutagenic intermediates. An endogenous bacterial acetylase plays an important auxiliary role in the hepatic S9-dependent activation of benzidine. Bacterial peroxidases may also support benzidine oxidation in the Ames test. PMID- 3091405 TI - Single-dose pharmacokinetics of clomiphene citrate in normal volunteers. AB - Twenty-four healthy adult female volunteers participated in a randomized, three phase double-blind crossover trial comparing the single-dose (50 mg) pharmacokinetics of three formulations of clomiphene citrate (CC). Plasma levels of both the Z(cis) and E(trans) isomers of CC, as well as principal metabolites, were determined at periodic intervals; and no differences between formulations were observed. The active Z isomer attained peak blood levels later than the inactive E isomer and was eliminated much more slowly, significant plasma concentrations still being detected up to 1 month after treatment. The results of this study demonstrate that three commercially available formulations of CC are bioequivalent. PMID- 3091406 TI - Gamete intrafallopian transfer in the treatment of infertility: the first series at the University of Palermo. AB - Twenty-six couples with unexplained infertility (UI), nine women with repeated failures of artificial insemination with donor semen (AID), three women with mild endometriosis, three with periadnexal adhesions, one with hostile (not immunologic) cervical mucus, and one couple in which the male partner was affected by asthenospermia were treated by the gamete intrafallopian transfer (GIFT) technique. Three different protocols for controlled ovarian hyperstimulation were used, and an adequate follicular growth and oocyte maturation were achieved in all cases. Seventeen pregnancies were obtained, for a global pregnancy rate of 38.6%. Two pregnancies (11.7%) ended in clinical abortions, and one (5.8%) was a tubal pregnancy. Of the ongoing pregnancies, one is twin and two are triplets. Seven pregnancies (six ongoing, one abortion) were obtained in the UI group (26%), six (all ongoing) in the failed AID group (66.6%), two continuing pregnancies in the three patients with endometriosis (66.6%); the tubal pregnancy and one clinical abortion occurred in the group with adnexal adhesions. No pregnancies were obtained in the patient with hostile cervical mucus and in the couple with infertility presumably due to poor semen. These encouraging results and the simplicity of the technique suggest that GIFT could be an effective approach that could be programmed during a well-timed laparoscopy where persistent infertility exists in association with apparently normal fallopian tubes. PMID- 3091407 TI - Cross-over trial of superovulation protocols from two major in vitro fertilization centers. AB - A study was undertaken as a controlled comparison of two different superovulation induction protocols currently in use in major Australian in vitro fertilization (IVF) clinics. Thirty patients each from the Monash University and the Royal Women's Hospital (RWH) IVF programs were stimulated for ovulation induction by the other program. Once timing for oocyte retrieval was scheduled, all care reverted to the program from which the patient first came. Results given as pregnancies per patient commencing stimulation were: RWH patients on Monash protocol, 27%; RWH control patients, 15%; Monash patients on RWH protocol, 7%; Monash control patients, 13%. In the year preceding the trial pregnancy rates were 16.9% at Monash and 10.6% at RWH. Stimulation protocols were also compared with respect to each of administration, cost, and patient stress. The results of this cross-over trial demonstrated major differences between the two ovulation induction protocols studied, although it was not possible to conclude that differences in pregnancy rate were due to stimulation alone. PMID- 3091408 TI - The treatment of infertility associated with endometriosis by in vitro fertilization. AB - In vitro fertilization and embryo transfer (IVF-ET) was performed on women with tubal disease only (28 women, 40 cycles), endometriosis grade I (15 women, 24 cycles), grade II (25 women, 37 cycles), grade III (26 women, 36 cycles), or grade IV (31 women, 52 cycles). Rates of oocyte recovery and fertilization were not affected by the presence of endometriosis. Pregnancy rates per cycle were similar to that of the tubal group (18%) for women with grade I (13%) or grade II (14%) endometriosis, lower in women with grade III endometriosis (6%) and significantly reduced in women with grade IV (2%, P less than 0.05). PMID- 3091409 TI - Sonography of the endometrium during conception and nonconception cycles of in vitro fertilization and embryo transfer. AB - The thickness of the endometrium was compared in 15 patients who conceived and 15 who did not with an in vitro fertilization and embryo transfer (IVF-ET) protocol after ovulation induction with human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG). There was no statistically significant difference (P = 1.0) in the endometrial thickness in the conception versus the nonconception group. Average estradiol (E2) values and number of mature follicles were also not statistically different in the two groups (P = 0.78, P = 0.81). There was a slightly significant difference in the number of embryos transferred in the conception versus nonconception groups (2.5 versus 1.9, P = 0.005). However, the most significant difference between the conception and nonconception groups was the total number of oocytes retrieved (4.4 versus 2.8, P = 0.005). These findings indicate that there are no sonographically detectable differences in the endometrial thickness in patients who achieve pregnancy versus those that do not when given a similar ovulation induction regimen of hMG/hCG for IVF-ET. PMID- 3091410 TI - Patterns of estradiol response in patients with endogenous gonadotropin surges during follicular recruitment in an in vitro fertilization and embryo transfer program. AB - This report is an analysis of 16 cycles in 15 patients stimulated with human menopausal gonadotropin and clomiphene citrate for the purpose of follicular recruitment in an in vitro fertilization program, all of which resulted in endogenous luteinizing hormone (LH) surges. A study of the pattern of estradiol (E2) response to stimulation revealed two groups of cycles, designated "leap" pattern (9 cycles) and "plateau" pattern (7 cycles), the rate of rise of E2 increasing or decreasing, respectively, as the time of the LH surge was approached. There were no significant differences between these groups of cycles in the peak E2 level attained or the number of follicles greater than or equal to 12 mm on the day of peak E2. In the plateau, but not in the leap pattern cycles, a significant correlation (r = 0.958) was found between the number of follicles greater than or equal to 12 mm and the peak E2. We tentatively conclude that "plateau" pattern cycles reflect relatively synchronous follicular recruitment; the greater the number of follicles recruited, the higher the E2 level attained, increased amounts of inhibin-like substances being available to restrain the LH surge; "leap" pattern cycles reflect asynchronous follicular recruitment. PMID- 3091411 TI - Factors influencing successful in vitro fertilization and embryo transfer: a matched pair study. AB - In the present matched-pair study successful and unsuccessful IVF-ET trials in patients with similar preconditions were compared. Sixteen consecutive cases of clinical pregnancies after IVF and ET were included. For each pregnant patient the subsequent patient who fulfilled the matching criteria and who did not conceive was chosen as a control subject. The matching criteria were the stimulation regimen and the number of embryos transferred. Pregnant and nonpregnant patients were compared with regard to their age, the total dosage of hMG, the cycle day at oocyte retrieval, the E2 levels 48 and 24 hours before laparoscopy, the E2 rise, the number of retrieved oocytes, and the cleavage rate. In both groups the investigated variables showed no significant difference between pregnant and nonpregnant patients. In patients with the same cycle stimulation and the same number of embryos transferred, successful implantation was not predictable by the evaluated parameters. PMID- 3091412 TI - Comparison of intermediate-dose purified urinary follicle-stimulating hormone with and without human chorionic gonadotropin for ovulation induction in polycystic ovarian disease. AB - Urinary FSH is capable of inducing ovulation in PCOD. The duration of treatment can be reduced by administering an intermediate dose. However, it appears that prospective monitoring with E2 assays and ultrasound, combined with hCG, is required to optimize outcome and minimize complications. Studies comparing urinary FSH with similar doses of hMG with and without hCG are needed to determine the most effective form of gonadotropin therapy in PCOD. PMID- 3091413 TI - The humoral antibacterial response of Drosophila adults. AB - Hemolymph from a normal adult Drosophila melanogaster lacks factors that block the growth of Escherichia coli, but hemolymph from a fly previously inoculated with Enterobacter cloacae inhibits bacterial growth. Antibacterial activity appears within two hours after inoculation, and is still detectable sixty days later. Activity is potent, and can be detected in as little as a quarter of the hemolymph from a single inoculated male fly. After inoculation, at least eight new polypeptides not of bacterial origin appear in hemolymph with a time course similar to the appearance of antibacterial activity; these are called Antibacterial Response Polypeptides, or ARs. The most prominent polypeptides are AR24, AR22, and AR19 with molecular weights of about 24, 22, and 19 kilodaltons (kd). Other bands with as much as 75 kd and as little as 5 kd were also found. Electrophoresis of active hemolymph under non-denaturing conditions, and isoelectric focusing separate several protein species that block bacterial growth (Antibacterial Proteins, or ABs); one AB is neutral (AB7.1) and three are basic (AB8.7, AB9.0 and AB9.2). Two dimensional gels show that AR24, AR22 and AR19 have pIs identical to the basic antibacterial proteins. Radiolabelling experiments proved that the ARs were synthesized de novo after bacterial inoculation. ARs in six species of Drosophila showed fundamentally similar electrophoretic patterns. PMID- 3091414 TI - Fetal carbon dioxide tension during human labour. AB - Fetal carbon dioxide tension during labour is elevated in both metabolic and respiratory acidosis, but intermittent fetal blood analyses often fail to detect PCO2 changes during acute complications. Transcutaneous carbon dioxide monitoring is continuous and the possibility of diagnosing PCO2 changes is therefore better. The theoretical background for transcutaneous measurements and methods for clinical monitoring are described. Close correlations with capillary and arterial blood values have been found, and the atraumatic principle with a simple electrode application indicates a promising new method for acid-base assessment during human labour. PMID- 3091415 TI - Effects of hyperinsulinism and of diabetes on proteoglycans of the intervertebral disc in weanling sand rats. AB - Weanling sand rats (Psammomys obesus) develop hyperinsulinemia or diabetes or both, if fed a standard laboratory diet without a supplement of fiber rich salt bush. The annuli fibrosi of hyperinsulinemic or diabetic animals, which are still hyperinsulinemic, show a slight but statistically significant increase in chondroitin sulfate and a lesser, statistically nonsignificant increase in keratan sulfate. Possible causes of these changes are discussed and the likelihood of a role of hyperinsulinism in their production is pointed out. PMID- 3091416 TI - Human brain hypoxanthine guanine phosphoribosyltransferase: structural and functional comparison with erythrocyte hypoxanthine guanine phosphoribosyltransferase. AB - A rapid and simple method, based on GMP Sepharose affinity chromatography, was used for the purification of human brain hypoxanthine guanine phosphoribosyltransferase. A single protein band was detected by polyacrylamide gel electrophoresis of the native purified enzyme. A subunit molecular weight of 25,000 was estimated by SDS gel electrophoresis. The Km values for hypoxanthine and phosphoribosyl pyrophosphate were 50 and 111 microM, respectively. The Ki values for GMP and IMP with phosphoribosyl pyrophosphate were 21 and 37 microM, respectively. The purified enzyme from human brain did not differ significantly from the human erythrocyte one in amino acid composition. The brain and erythrocyte hypoxanthine guanine phosphoribosyltransferases showed complete immunochemical identity on Ouchterlony double diffusion. PMID- 3091417 TI - DNA polymerases of rabbit mammary gland: partial purification, characterization and changes in DNA polymerase activities as a function of physiological state. AB - DNA polymerases alpha and beta were partially purified from rabbit mammary gland, and their properties were examined. Many of these properties (sedimentation coefficients, pH optima, divalent cation requirements, sensitivity to various inhibitors) are similar to those commonly regarded as typical of eukaryotic DNA polymerases alpha and beta. Effect of stage of pregnancy and lactation on the levels of activity of DNA polymerases alpha, beta and gamma in rabbit mammary gland was examined. These experiments reveal a considerable variation of DNA polymerase-alpha activity; the highest enzyme activity is observed on day-20 of pregnancy and on day-1 of lactation. PMID- 3091418 TI - Receptor mediated endocytosis of formaldehyde treated albumin, yeast invertase and chondroitin sulfate in suspensions of rat liver endothelial cells. AB - Isolated rat liver endothelial cells take up and degrade formaldehyde serum albumin (FSA), invertase and chondroitin sulfate (CS) efficiently. Degradation products start to appear in the medium after 5-30 min. Calcium was necessary for binding of invertase to the cells, but not for the two other ligands. Ammonia and monensin inhibited uptake as well as degradation of all three ligands, whereas leupeptin only inhibited the degradation of FSA and invertase. Uptake of CS was strongly inhibited in the presence of 1 microM FSA. The possibility that these two ligands bind to a common receptor is discussed. PMID- 3091419 TI - The isolation and purification of a proteinase with chymotrypsin-like properties from ovine mucosal mast cells. AB - A mast cell granule proteinase was purified from isolated ovine mucosal mast cells by cation exchange chromatography, which defined the conditions for enzyme purification from sheep gastric mucosae. Antibodies raised against the proteinase were used in subsequent purification procedures which yielded 78 micrograms of enzyme per 5 g wet wt of abomasal tissue. Immuno-histochemistry confirmed that mucosal mast cells were the source of the enzyme. The proteinase had chymotrypsin like esterase activity, with a molecular weight between 19,000 and 25,000. PMID- 3091420 TI - Beta-galactosidase in the seminal plasma and reproductive organs of the bull. AB - The distribution of beta-galactosidase activity was studied in different reproductive organs, seminal plasma and spermatozoa of the bull. The highest specific activity of beta-galactosidase was found in testis and in different parts of the epididymis, where the activity seemed to be partly in secretory (cauda secretion) and partly in non-secretory, bound form (caput to cauda epididymidis). Gel filtration on Sepharose 6B at pH 7.0 revealed two beta galactosidase forms (GF-1, Mr approximately 500,000-600,000 and GF-2, Mr approximately 190,000-220,000) in reproductive organs and seminal plasma. The pH optimum of both beta-galactosidase forms was about 3.75-4.75. Hg2+ and p chloromercuribenzoate inhibited strongly these activities. Further, form GF-2 seemed to be slightly more sensitive to the thermal inactivation at 50-70 degrees C than form GF-1. In chromatofocusing beta-galactosidase activities in bull seminal plasma coeluted with those of the cauda epididymidis (pI-values 7.5-6.4). On the contrary, prostate, Cowper's gland, testis, ampulla and seminal vesicles had enzyme activities eluting at lower pI-values (6.3-4.2). Thus, the seminal plasma activity is mainly an indicator for the function of the epididymal cauda. PMID- 3091421 TI - Kinetic and structural properties of biocatalytically active sheep lung microsomal NADPH-cytochrome c reductase. AB - NADPH-cytochrome c reductase was purified to electrophoretic homogeneity from detergent solubilized sheep lung microsomes. The specific activity of the purified enzyme ranged from 56 to 67 mumol cytochrome c reduced/min/mg protein and the yield was 48-52% of the initial activity in lung microsomes. The reductase had Mr of 78,000 and contained 1 mol each of FAD and FMN. Km values obtained in 0.3 M phosphate buffer, pH 7.8 at 37 degrees C for NADPH and cytochrome c were 11.1 +/- 0.70 microM and 20.0 +/- 2.15 microM. Lung reductase was inhibited by its substrate, cytochrome c when its concentration was above 160 microM. The lung reductase exhibited a ping-pong type kinetic mechanism for NADPH mediated cytochrome c reduction. Purified lung reductase was biocatalytically active in supporting benzo(a)pyrene hydroxylation reaction when coupled with lung cytochrome P-450 and lipid. PMID- 3091422 TI - Inter-tissue relationships in the synthesis and distribution of carnitine. PMID- 3091423 TI - Melatonin's differential inhibition of FSH and LH release from hamster pituitary glands. AB - Melatonin initially inhibited FSH secretion from superfused adult male hamster anterior pituitary glands obtained at 8:30 a.m. However, there was a gradual rebound during melatonin superfusion followed by an overshoot above baseline when melatonin was discontinued (morning response). Melatonin continuously inhibited FSH secretion during superfusion of hamster anterior pituitary glands obtained at 3:30 p.m., with a rebound evident only when melatonin was withdrawn (afternoon response). Melatonin continuously inhibited LH secretion from these superfused pituitaries, with a return to baseline levels only upon melatonin withdrawal. Prior pinealectomy or constant light could reverse the FSH morning response to an afternoon response, and late-morning melatonin injections could reverse the FSH afternoon response to a morning response. Neither prior pinealectomy, constant light nor melatonin injections affected melatonin inhibition of LH secretion from superfused pituitary glands. These results suggest that melatonin differentially inhibits FSH and LH secretion from isolated superfused hamster anterior pituitary glands. PMID- 3091424 TI - Effect of melatonin in vivo upon FSH and LH release from hamster pituitary glands. AB - The effect of chronic daily afternoon injections of melatonin upon basal and melatonin-modulated release of FSH and LH was investigated in superfused hamster anterior pituitary glands. The basal release rate of both FSH and LH began to decline following the beginning of melatonin injections, and reached a nadir after six weeks. Basal release rate of FSH and LH then began to spontaneously increase and reached a plateau at 13 weeks of injections. The inhibition by melatonin upon FSH and LH release in vitro gradually declined during the period of melatonin injections. After six weeks of melatonin injections the release rate of FSH was no longer suppressed by melatonin superfusion, while the release rate of LH became refractory to melatonin suppression in vitro after nine weeks of melatonin injections. These results demonstrate a change in the release rates of both basal and melatonin-inhibited gonadotropin release during melatonin-induced testicular regression and recrudescence in hamsters. PMID- 3091425 TI - Effects of in vivo bolus versus continuous TRH administration on TSH secretion, biosynthesis, and glycosylation in normal and hypothyroid rats. AB - The effects of in vivo TRH administered either as bolus or continuous doses on TSH secretion, synthesis, and glycosylation were studied in normal and hypothyroid rats. Nine-week-old normal or 3-week postthyroidectomy rats were administered bolus doses of saline or TRH (0.5 mg/kg) twice daily or continuous saline or TRH (1 mg/kg/day) via an osmotic pump. After 5 days, pituitaries were removed and incubated with [35S]methionine (MET) and [3H]glucosamine (GLCN), with or without 10(-8) M TRH, for 6 and 24 h. Samples were precipitated with anti-TSH beta sera and then analyzed by gel electrophoresis. In normal rats, plasma TSH, T4 and T3 increased with continuous in vivo TRH but not with bolus TRH; in hypothyroid rats, plasma TSH, T4 and T3 were not altered by continuous or bolus doses of TRH. Additionally, in normal rats, continuous in vivo TRH increased incorporation of MET in secreted TSH (477 vs. 212 X 10(3) dpm/mg DNA; P less than 0.05) and intrapituitary TSH (5035 vs. 2124 X 10(3) dpm/mg DNA; P less than 0.05), and GLCN in secreted TSH (148 vs. 50 dpm/mg DNA; P less than 0.05) and intrapituitary TSH (2344 vs. 744 X 10(3) dpm/mg DNA; P less than 0.05). In contrast, in hypothyroid animals, continuous in vivo TRH did not alter MET or GLCN incorporation in TSH. Bolus TRH did not alter secreted or intrapituitary MET or GLCN incorporation into TSH in the normal rat. However, bolus TRH in the intrapituitary MET or GLCN incorporation into TSH in the normal rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091426 TI - Glomerular mesangial cell contractility in vitro is controlled by an angiotensin prostaglandin balance. AB - Rat renal mesangial cells possess morphological and functional features of smooth muscle cells in culture, such as intracellular myosin filaments, A II receptors and a contractile response to A II. Furthermore, they represent the main glomerular site of PGE2 synthesis. In the presence of A II (50 nM), their PGE2 production rate was significantly increased, this effect being potentiated by arachidonic acid (3 micrograms/ml). After a prior inhibition of arachidonic acid metabolism by cyclooxygenase inhibitors (indomethacin 1 microM or naproxen 0.02 microM) or by a cyclo- and lipoxygenase inhibitor (phenidone 670 microM), the percentage of cells contracting in response to various A II concentrations (10 pM to 10 nM) was significantly enhanced as compared to the basal conditions. On the contrary, the percentage of cells presenting a contractile response to A II in the presence of exogenous PGE2 (50 ng/ml) or of arachidonic acid (3 micrograms/ml) was significantly decreased. These modifications were not related to some changes in the A II receptor properties of the cells, i.e. the number of receptor sites and their affinity constant. The data demonstrate that the contractile response of glomerular mesangial cells is modulated by the PGE2 content of their incubation medium. Since their own PGE2 production rate is enhanced in the presence of A II, this cellular response may represent a local regulatory mechanism of their contractile properties. PMID- 3091427 TI - Effects of repeated stimuli on prolactin release in vitro from normal and adenomatous rat lactotrophs. AB - It is now well known that dopamine (DA) plays a major role in the inhibitory control of prolactin (PRL); however, the mechanisms that are physiologically involved in the stimulation of PRL release are still under investigation. Indeed, although suppression of DA inhibitory tonus, administration of thyrotropin releasing hormone (TRH) or vasoactive intestinal peptide (VIP) are all known PRL releasers, it is not clear whether they interact during physiological periods of PRL release such as suckling and estrus. No clear indications exist, furthermore, on whether they all act upon a same pituitary pool that may become depleted following repeated exposure to stimuli. Refractoriness to a single or a repeated stimulus has been reported to occur in prolactinoma-bearing or normal humans, respectively, the mechanism of which is still matter for discussion. Our present studies performed by perifusing normal or adenomatous rat lactotrophs attached to Cytodex I microcarrier beads was undertaken to try and answer some of these questions. The experimental period consisted in perifusing the cells for 1 h with Dulbecco's modified Eagle's medium (DMEM) containing DA 10(-5) M, then for 2 h with either DMEM, DMEM and TRH 10(-8) M, DMEM and VIP 10(-7) M, then again with DA in DMEM for 1 h, and finally with DMEM, DMEM and TRH, or DMEM and VIP. Three experiments of various combinations were performed. Lower PRL levels were observed under DA, while two periods (first and second) of PRL release followed the suppression of DA infusion with or without the addition of either one of the two peptides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091428 TI - A calcium-activated sodium conductance contributes to the fertilization potential in the egg of the nemertean worm Cerebratulus lacteus. AB - The fertilization potential of the egg of the nemertean worm Cerebratulus lacteus consisted of a rapid shift from a resting potential of about -65 mV to a peak of about +44 mV; the peak was followed by a positive plateau at about +24 mV, lasting an average of 80 min. Reduction of extracellular calcium reduced the peak of the fertilization potential, indicating that the peak resulted from a calcium conductance, while reduction of extracellular sodium reduced the plateau potential, indicating that the plateau resulted from a sodium conductance. Microinjection of ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) or 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)/CaBAPTA buffers, having a free calcium concentration of less than or equal to about 0.1 microM lowered the fertilization potential plateau. Injection of a BAPTA/CaBAPTA mixture with a free calcium concentration of about 1 microM resulted in a prolonged positive potential at the level of the fertilization potential plateau. These observations indicated that the fertilization potential of the Cerebratulus egg depended on a calcium-activated sodium conductance. The plateau potential was reduced little, if any, when calcium-free seawater was perfused through the bath during the fertilization potential; nor was it reduced in seawater containing cadmium. These observations suggested the possibility that intracellular calcium stores could be important in producing the fertilization potential. PMID- 3091429 TI - Muscle degeneration in the posteclosional development of a Drosophila mutant, abnormal proboscis extension reflex C (aperC). AB - The aperC (abnormal proboscis extension reflex C) mutation in Drosophila melanogaster causes a defect in the proboscis extension reflex (PER) in aged flies. Young flies of the mutant show an apparently normal PER. When aperCTF36 mutants were reared at 25 degrees C, the flies became unable to extend the proboscis at Day 5 of eclosion, but within a few days, many of them recovered the PER. When reared at 18 degrees C, the mutants showed a defective PER, but did not show the recovery. At 29 degrees C, only a limited number of the mutant flies showed the defective PER. Histological inspection of the mutant revealed that the degeneration occurs in a pair of muscles, the rostral protractors, which are involved in the extension of the rostrum. The degeneration of the muscle was observed in the mutant by polarizing light microscopy. The cross striation disappeared from the central portion of the muscle fibers at Day 3. Birefringence of the fibers also disappeared. At Day 10 the degenerated muscle fibers showed regeneration. The PER was closely correlated with the degree of muscle degeneration and regeneration. Temperature-shift experiments indicated that the temperature-sensitive-period of the aper CTF36 mutation occurs around Days 2-4 after eclosion. Results indicate that the aperC+ gene regulates the posteclosional maintenance of the muscle fibers. PMID- 3091430 TI - Replication and expression of an X-linked cluster of Drosophila chorion genes. AB - Two 80- to 100-kb chromosomal replicons containing clustered chorion genes amplify in the ovarian follicle cells during the final 22 hr of Drosophila oogenesis. We have studied the relationship between amplification and transcription within one of these domains, located at 7E10-7F3,4 on the X chromosome. A tandem cluster of six genes, encoding chorion structural proteins s36-1, s38-1, and four putative minor chorion protein mRNAs, was mapped in the central 18 kb of the amplified domain, a region showing the highest levels of amplification. The regions both proximal and distal to this gene cluster, where lower levels of amplification occur, were also transcribed in ovary, but mRNAs produced specifically during choriogenesis were not detected. Thus, differences in amplification do not appear to modulate differential RNA accumulation. Instead, the gradient of amplification observed in egg chamber DNA may simply reflect the mechanism of amplification. In the female sterile mutation, In(1)ocelliless, a chromosomal rearrangement separates the central gene cluster into two parts, only one of which retains the capacity to amplify. Genes located within the unamplified portion of the ocelliless chromosome were expressed at the appropriate time during oogenesis, but at a 5- to 10-fold reduced level of RNA per gene. Thus neither cluster integrity nor amplification are required for the normal developmental program of gene expression within the cluster. PMID- 3091431 TI - Disruption of positional fields in apterous imaginal discs of Drosophila. AB - Certain combinations of alleles at the apterous locus generate wings with extra copies of wing margin structures, some of which are located far from the normal margin. We have examined wing imaginal discs from these mutants, using position specific antibodies as probes for two-dimensional patterning in the discs. Our results indicate that the adult phenotypes arise from unprecedented disruptions in the two-dimensional pattern of the disc epithelia. Examination of other apterous mutants suggest that pattern alterations may be a general consequence of lesions at this locus. PMID- 3091432 TI - Analytical, toxicological and immunological consequences of the use of N-ethyl-N' (3-dimethylaminopropyl) carbodiimide as coupling reagent for the preparation of meningococcal group C polysaccharide-tetanus toxoid conjugate as vaccine for human use. AB - For the preparation of meningococcal group C polysaccharide-tetanus toxoid conjugate the reactive reagent N-ethyl-N'-(dimethylaminopropyl) carbodiimide is used. The application of this reagent results in a number of stable linkages (viz. "peptide" linkages between the polysaccharide and tetanus toxoid, intrachain ester linkages in the polysaccharide component and binding of the N acylurea derivative of the reagent) and less stable ones (viz. anhydride linkages). As a consequence of the reaction, the reagent is converted to a non reactive urea derivative. The toxic properties of the reagent and of the converted reagent were studied. These properties do not contraindicate the use of the coupling reagent for the preparation of vaccines for human use. In addition analytical methods have been developed for the quantitative evaluation of the coupling reagent, the reaction products and for the N-acylurea derivative of the reagent and of the residual reactivity of conjugates for primary aminogroups. Although no test was performed for the assay of ester linkages in the polysaccharide component of the conjugate, evidence is presented that such linkages may be present. The results of the test for residual reactivity indicated a spontaneous rearrangement of linkages after the preparation of the conjugate. In addition the influence of the ratio of coupling reagent-to polysaccharide and tetanus toxoid on antigenic and immunogenic activities of the conjugate was studied. An increase of the ratio resulted in a decrease of the antigenic activity of the polysaccharide component but in an increase of its immunogenic activity as to the induction of IgG antibodies to the polysaccharide. The immunogenic activity of the polysaccharide component correlated rather well with the antigenic activity measured in heterologous enzyme-linked immunosorbent assay using antibodies to both components. PMID- 3091433 TI - Class 1/3 outer membrane protein vaccine against group B, type 15, subtype 16 meningococci. AB - Neisseria meningitidis capsular polysaccharides and outer membrane proteins have been incorporated in vaccines and the potential of these vaccines has been evaluated in man. Polysaccharides are the most attractive candidates for a vaccine against group A and C meningococci whereas outer membrane proteins may have a potential for a vaccine against group B meningococci. This paper describes the characteristics of the five classes of outer membrane proteins of group B meningococci and the protective (bactericidal) activity of monoclonal antibodies against class 1 and 2 or 3 outer membrane proteins. Monoclonal antibodies against class 1 outer membrane proteins were bactericidal irrespective of the growth conditions of the bacterium. On the other hand, these conditions influenced the bactericidal activity of monoclonal antibodies against class 2 or 3 outer membrane proteins. These data indicate that class 1 outer membrane protein is an attractive component of a vaccine. The Blake and Gotschlich procedure for the isolation of gonococcal outer membrane protein II (1) was adapted for the isolation of a combination of class 1 and 3 outer membrane proteins from group B, type 15 meningococci. The combination of both outer membrane proteins was adsorbed to ALPO4 in the presence of the detergent Zwittergent 3-14. The vaccine was injected into mice. The antibodies were strongly bactericidal and Western blot analysis indicated that both outer membrane proteins induced antibodies. The vaccine may have a potential to combat an epidemic caused by group B, type 15 meningococci. Such an epidemic was observed in some N.W. - European countries. PMID- 3091434 TI - Plasma level of 13,14-dihydro-15-keto-PGE2 in patients with diabetic ketoacidosis and in normal fasting subjects. AB - Plasma levels of 13,14-dihydro-15-keto-PGE2, a stable derivative of PGE2, are elevated in rats with diabetic ketoacidosis (DKA) and decrease in response to insulin therapy. In patients with insulin-dependent diabetes mellitus type I (IDDM) the plasma levels of this derivative also rise in response to insulin withdrawal and then fall in response to insulin replacement. We wished to determine whether the level of this substance is elevated acutely when patients present with DKA and to determine whether the levels fall during treatment. We also wished to identify the origin of the circulating 13,14-dihydro-15-keto-PGE2 in patients with DKA and in normal fasting subjects. We measured the plasma level of 13,14-dihydro-15-keto-PGE2 in five patients with DKA and in six normal subjects during a 24-h fast. In the patients with DKA before treatment, the plasma 13,14-dihydro-15-keto-PGE2 level was threefold above normal. During therapy, the 13,14-dihydro-15-keto-PGE2 level fell toward normal. There was a significant direct correlation between the plasma free fatty acid (FFA) level and the plasma 13,14-dihydro-15-keto-PGE2 level before and during treatment. In addition, the inverse correlation between the plasma free-insulin level and the plasma 13,14-dihydro-15-keto-PGE2 level approached significance (P = .06). In contrast, in the normal fasting subjects the plasma FFA level rose to values comparable to those observed in the patients with DKA, but there was no significant increase in the plasma 13,14-dihydro-15-keto-PGE2 level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091435 TI - Metabolic fate of plasma diamine oxidase: evidence of isolated and perfused rat liver uptake. AB - After injection of an intravenous bolus of heparin (15,000 IU) in two groups of subjects, 10 normal volunteers and 6 subjects with external biliary drainage, blood and urine samples were collected; in the latter group bile samples were collected also. All samples were assayed for diamine oxidase (DAO). Persistently high values of this enzyme were found in plasma of both populations after heparin stimulation, while no increase in enzymatic activity was detected in bile and urine. In order to confirm and support the hepatic clearance of DAO, liver uptake of the enzyme derived from porcine kidney, human plasma and human placenta was studied by perfusion of isolated rat liver. Disappearance curves of the enzyme derived from three different sources showed a prompt liver uptake: activity decreased by about 50% in 10 min (endocytic uptake) and a slower but constant reduction during the remaining 110 min of perfusion was observed. These data suggest the hypothesis of liver metabolism of plasma DAO. PMID- 3091436 TI - Role of endogenous prostaglandins in duodenal alkaline response to luminal hydrochloric acid or arachidonic acid in conscious dogs. AB - Duodenal secretion of HCO-3 and luminal release of PGE2 were measured in conscious dogs. The results show that the HCO-3 secretion is closely correlated with the luminal release of PGE2 and that both the HCO-3 and the PGE2 outputs increase dose-dependently after topical application of hydrochloric acid or arachidonic acid. Indomethacin reduced basal HCO-3 and PGE2 release and prevented their increase in response to hydrochloric acid or arachidonic acid. We conclude that mucosal PGE2 plays an important role in the alkaline secretion from the duodenum. PMID- 3091437 TI - Islet transplants in diabetic Lewis rats prevent and reverse diabetes-induced increases in vascular permeability and prevent but do not reverse collagen solubility changes. AB - The effects of islet transplantation on diabetes-induced increases in vascular permeability and collagen solubility were examined in new granulation tissue vessels and collagen formed after induction of streptozotocin diabetes in male Lewis rats. Albumin permeation was increased by 50% (p less than 0.001) and collagen solubility was decreased by 50% (p less than 0.001) in granulation tissue from untreated diabetic animals as compared with controls. The islet transplants reversed diabetes-induced vascular permeability increases in tissues formed prior to islet transplantation (tissue to blood isotope ratio = 2.1 +/- 0.1 - SD for controls, 3.2 +/- 0.2 for diabetic rats and 2.0 +/- 0.2 for diabetic rats given islets) and prevented permeability increases in new tissues formed following transplantation (tissue to blood isotope ratio = 2.1 +/- 0.1 for controls, 3.3 +/- 0.8 for diabetic rats and 1.9 +/- 0.2 for diabetic rats given islets). In contrast, while islet transplants prevented diabetes-induced decreased collagen solubility in tissues formed after transplantation (controls = 24%, diabetic rats = 12%, and diabetic rats given islets = 24%), collagen solubility in tissues formed prior to islet transplantation was virtually unaffected. These findings indicate that collagen changes induced by the diabetic milieu are not nearly as readily reversed by normalization of the diabetic milieu as (diabetes-induced) alterations in vascular functional integrity. PMID- 3091438 TI - Vasopressin and diabetic ketoacidosis. PMID- 3091439 TI - Self-renewal and differentiation of interleukin-3-dependent multipotent stem cells are modulated by stromal cells and serum factors. AB - Interleukin-3 (IL-3)-dependent cell lines (FDCP-mix) were cloned and isolated from long-term bone-marrow cultures infected with src-MoMuLV. These cell lines have many of the characteristics of hematopoietic stem cells. Early isolates of the FDCP-mix cells form spleen colonies in irradiated mice and establish long term hematopoiesis on irradiated marrow stroma in vitro in the absence of IL-3. These two properties of the cells are lost within 15 weeks of establishing the cell lines, but the cell lines retain their ability to differentiate in a multilineage response to hematopoietic growth factors and to hematopoietic stromal cells, as well as to self-renew in the presence of IL-3. The choice between differentiation and self-renewal in FDCP-mix cells can clearly be modified by culture conditions: in particular, cultures containing horse serum preferentially promote self-renewal, whereas cultures containing fetal calf serum preferentially promote differentiation. The FDCP-mix cell lines are not leukemic, nor do they contain the src oncogene. Their ability to respond to hematopoietic growth factors and stroma in a similar manner to normal hematopoietic cells makes them a valuable model for studying the regulation of hemopoietic cell self renewal and differentiation. PMID- 3091440 TI - [Experimental atherogenesis]. AB - The arterial wall possesses homeostatic mechanisms which are fundamental to the maintenance of its anatomical and functional integrity. The relative or absolute insufficiency of such mechanisms can lead with time to vascular disease, not the least of which is atherosclerosis. The understanding of the physiology of the arterial wall seems therefore necessary to a better approach to the study of several pathological processes. Four cell types play a critical role in the response of the vascular wall to physiological and pathological stimuli. They are the endothelial cell, the smooth muscle cell, the monocyte/macrophage and the platelet. The ordered interaction among these cell types is responsible for the maintenance of vascular integrity and, thus, for an efficient arterial response to physiological stimuli. Thus, it can be conceptually said that atherosclerosis derives from an excessive biological response to pathological stimuli. The current knowledge on the properties and potential interactions among each of the cells present and interacting with the arterial wall in relation to physiological mechanisms and atherogenic stimuli is discussed. PMID- 3091441 TI - A simplified technique for constructing a feeding jejunostomy from an existing gastrostomy. PMID- 3091442 TI - [Hyperthecosis ovarii--a tumor-like change in androgenized females]. AB - Hyperthecosis has been repeatedly described as a disease entity separate from polycystic ovaries (PCO) as characterised by stromal luteinisation, obligatory virilism and purely ovarian androgen hypersecretion. This study compares the findings in patients with hyperthecosis (n = 10), PCO (n = 33) and androgen secreting ovarian tumours (n = 7). It included selective ovarian-adrenal vein catheterisation with measurement of testosterone (T), dihydro-T, androstenedione, DHEA and its sulfate, 17 alpha-hydroxyprogesterone and cortisol before and after dexamethasone; determination of free T, oestrone, oestradiol and prolactin as well as LH and FSH before and after GnRH. In histologically proven hyperthecosis, signs of virilism were absent in 6 cases. A specific hormone profile could not be identified. Mixed ovarian-adrenal androgen hypersecretion was documented in 4 patients (purely ovarian: n = 6). Ovarian T output frequently fell within the tumour range (n = 4). It is concluded that the minor differences between hyperthecosis and PCO represent only variable manifestations of the same heterogeneous disturbance of androgen metabolism. However, it is of special clinical relevance to rule out a tumour in patients with hyperthecosis. PMID- 3091443 TI - [Parenteral feeding of patients with leukemia]. PMID- 3091444 TI - [Study of iron metabolism in practically healthy young men using whole body radiometry for the detection of latent iron deficiency anemia]. PMID- 3091445 TI - [Use of polyamine for parenteral and enteral-tube administration]. PMID- 3091446 TI - The question of the total gene number in Drosophila melanogaster. AB - A statistical analysis has been carried out on the distribution and allelism of nearly 500 sex-linked, X-ray-induced, cytologically normal and rearranged lethal mutations in Drosophila melanogaster that were obtained by G. Lefevre. The mutations were induced in four different regions of the X chromosome: (1) 1A1 3E8, (2) 6D1-8A5, (3) 9E1-11A7 and (4) 19A1-20F4, which together comprise more than one-third of the entire chromosome.--The analysis shows that the number of alleles found at different loci does not fit a Poisson distribution, even when the proper procedures are taken to accommodate the truncated nature of the data. However, the allele distribution fits a truncated negative binomial distribution quite well, with cytologically normal mutations fitting better than rearrangement mutations. This indicates that genes are not equimutable, as required for the data to fit a Poisson distribution.--Using the negative binomial parameters to estimate the number of genes that did not produce a detectable lethal mutation in our experiment (n0) gave a larger number than that derived from the use of the Poisson parameter. Unfortunately, we cannot estimate the total numbers of nonvital loci, loci with undetectable phenotypes and loci having extremely low mutabilities. In any event, our estimate of the total vital gene number was far short of the total number of bands in the analyzed regions; yet, in several short intervals, we have found more vital genes than bands; in other intervals, fewer. We conclude that the one-band, one-gene hypothesis, in its literal sense, is not true; furthermore, it is difficult to support, even approximately.--The question of the total gene number in Drosophila will, not doubt, eventually be solved by molecular analyses, not by statistical analysis of mutation data or saturation studies. PMID- 3091447 TI - The absence of somatic effects of P-M hybrid dysgenesis in Drosophila melanogaster. AB - The wings and abdomens of dysgenic and nondysgenic control flies were scored for the presence of clones of cells mutant for first and third chromosome markers. These exceptional clones can arise from mitotic recombination, de novo mutation or deletion, and P-M hybrid dysgenesis has been shown to increase the frequency of parallel processes occurring in germ-line cells. Particular attention was given to careful genetic and molecular characterization of all stocks and to providing adequate and appropriate controls so that even very small increases in somatic clone frequency due to P-M hybrid dysgenesis would be detected. No difference was found in the frequency, size distribution or anatomical distribution of mutant somatic clones correlated to hybrid dysgenesis, confirming previous indications. The potential adaptive significance of a germ-line restriction of P-M hybrid dysgenesis is discussed. PMID- 3091448 TI - Temporal variation for the expression of catalase in Drosophila melanogaster: correlations between rates of enzyme synthesis and levels of translatable catalase-messenger RNA. AB - Two variants that alter the temporal expression of catalase have been isolated from a set of third chromosome substitution lines. Each variant has been mapped to a cytogenetic interval flanked by the visible markers st (3-44.0) and cu (3 50.0) at a map position of 47.0, which is within or near the interval 75D-76A previously identified as containing the catalase structural gene on the bases of dosage responses to segmental aneuploidy. Each variant operates by modulating the rate of enzyme synthesis and the level of translatable catalase-mRNA. PMID- 3091449 TI - Genetic controls over activities of tyrosinase and dopachrome conversion factor in murine melanocytes. AB - We evaluated the three catalytic activities of tyrosinase and one activity of dopachrome conversion factor (DCF) in extracts made from skins of 6-day-old yellow and nonyellow mice. At least one of the catalytic activities of tyrosinase and of DCF correlate with the color of pigment being produced in the hair follicles of the mice. We use these data to evaluate existing hypotheses about the mechanism of the interacting genetic controls over melanogenesis. PMID- 3091451 TI - [Differences in the allele state of genes controlling the specificity of adsorption in transposable phages of Pseudomonas aeruginosa]. AB - To reveal possible differences in adsorptional specificities of transposable phages of Pseudomonas aeruginosa and to study the genetical control of this character, we isolated a group of phage-resistant P. aeruginosa mutants using some temperate and virulent phages. The study of resistance of the mutants to all the phages permitted us to find some types of mutants and to build a formal scheme of distribution of adsorptional receptors on the surface of P. aeurginosa cell. According to the results obtained, there are two main "receptor chains", where the receptors for all phages under study are grouped. For the majority of phages, just a single adsorptional receptor is obligatory, and at least two essential receptors are needed for adsorption of virulent phage E79. Two receptors were found also for another virulent phage, phi 11, one of them only being essential. Transposable phages can be grouped into three types, according to their adsorptional specificities. No correlations of adsorptional specificity types and all other characteristics of transposable phages studied (including the sub-groups of transposable phages belonging to different DNA homology types) were found. Genes of natural transposable phages controlling the differences in adsorptional specificities revealed can recombine in phage crosses. PMID- 3091450 TI - Immunogenetic polymorphism of lipoproteins in swine: genetic, immunological and physiochemical characterization of the two allotypes Lpr1 and Lpr2. AB - Results of immunogenetic, immunochemical and physicochemical investigations on two serum allotypes of swine are reported. The allotypes, designated Lpr1 and Lpr2, have been identified by specific alloprecipitins in agar gel. Genetic studies indicate that the allotypes are specified by two codominant autosomal allelic genes, Lpr1 and Lpr2. All pigs 3 months of age or older were classified as belonging to one of three phenotypes, Lpr1, Lpr2 or Lpr1,2, each corresponding to one of three genotypes Lpr1/1, Lpr2/2 or Lpr1/2, respectively. The Lpr1 gene was absent or was found at low frequency in the breeds tested. The allotypes were found to occur in two physicochemical forms; in association with chylomicrons and very low density lipoproteins (VLDL) and, primarily, as a Lpr multimer free of the major lipoproteins showing very high density (VHD), d greater than 1.21 g/ml, and MW +/- 190,000. Gel-electrophoretic mobility for VHD-Lpr is different for each of the three Lpr genotypes residing in gamma-fast and beta-slow regions, but is identical for VLD-Lpr in which Lpr was found complexed with apo-B, migrating as VLDL in the alpha-2 slow (pre-beta) region. Serum levels of Lpr varied during the lifetime and between individuals and, especially, between sera of homozygous pigs being higher in Lpr1/1 than Lpr2/2. A linear relationship for Lpr1 and an atypical, inverse relationship for Lpr2 have been observed between the gene dosage, heterozygous vs. homozygous, and the Lpr serum level. PMID- 3091452 TI - [Behavior of autonomous plasmids and plasmids integrated into the chromosome during the sporulation of Bacillus subtilis cells]. AB - The behaviour of plasmids in free and integrated states was studied upon sporulation of Bacillus subtilis cells. Autonomous plasmids pBD12 and pGG10 were shown to be either transmitted into spores in small copy numbers or completely eliminated from the sporulating cell. However, insertion of the autonomous plasmid into the host chromosome may occur with a certain degree of probability (about 10(-3)) during sporulation. When in the integrated state, pBD12 plasmid may either excise from the host chromosome or amplify within the genome with the probability 1.8-2.10(-3) in the course of sporulation. The pGG102 plasmid carrying the fragment of wheat DNA and integrated by this fragment into the chromosome was shown to enter spores without whichever intragenome rearrangements. PMID- 3091453 TI - Hybrid dysgenesis in Drosophila melanogaster: synthesis of RP strains by chromosomal contamination. PMID- 3091454 TI - Cloning and structural analysis of the calf prochymosin gene. AB - Calf prochymosin (cPC) gene was cloned from calf abomasum DNA by using a cloned cPC cDNA as a probe. The cPC gene spans approx. 10.5 kb and consists of 9 exons and 8 introns. The positions of exon-intron junctions coincide completely with those in the human pepsinogen gene. Analysis of 5'-flanking region sequence and S1 nuclease mapping revealed that the transcriptional start point was located 25 bp upstream from the start codon and that the putative transcriptional promoter sequences (TATA box and CCAAT box) were located in -30 and -90 regions, respectively. Some distinctive sequences possibly functioning as regulatory signals for gene expression are present at the 5'-flanking region. PMID- 3091455 TI - Construction of high, intermediate and low-copy-number promoter-probe plasmids for Bacillus subtilis. AB - We constructed promoter-probe plasmids for Bacillus subtilis based on the promoterless gene for penicillinase (penP) of Bacillus licheniformis. A Bacillus stearothermophilus DNA fragment, which contained translational stop codons for all three reading frames and transcription terminators of the alpha-amylase gene, was inserted upstream from the Shine-Dalgarno sequence for the penP gene. A low copy-number plasmid (about 10 copies per chromosome), pPF101, carried tetracycline-resistance gene, whereas another high-copy-number plasmid (about 55 copies per chromosome), pPF201, conferred resistance to kanamycin. The intermediate-copy-number plasmids (about 20 copies per chromosome), pPF001, pPF002, pPF011 and pPF012, conferred chloramphenicol resistance to both B. subtilis and Escherichia coli. Vector plasmids, pPF011 and pPF012, were provided with single cloning sites for BamHI, SacI, SmaI and XbaI upstream from the protein coding region of penP, whereas other plasmids contained only unique BamHI cloning sites. The applicability of these plasmids was demonstrated by cloning a promoter for the alpha-amylase gene. PMID- 3091456 TI - Nucleotide sequence of gene linA encoding resistance to lincosamides in Staphylococcus haemolyticus. AB - We have determined the nucleotide sequence of gene linA in plasmid pIP855, which confers resistance to lincomycin by inactivating it in Staphylococcus haemolyticus. The gene was defined by start and stop codons and an open reading frame of 483 bp corresponding to a product with an Mr of 19020. The apparent size of the resistance-conferring protein was 21 kDa, when a minicell extract was electrophoresed in the sodium dodecyl sulfate-polyacrylamide gels. Full expression of linA was obtained both in Escherichia coli and Bacillus subtilis. PMID- 3091457 TI - Plasmid vectors useful in the study of translation initiation signals. AB - The construction and characterization of plasmid vectors useful in the analysis of translation initiation signals in Escherichia coli and in the construction of lacZ gene hybrids are described. Transcription on the vectors proceeds from a cAMP-independent lac promoter through several restriction sites into a truncated lacZ structural gene lacking its first eight codons. Because this gene has no translation initiation signal, its level of expression is extremely low. A DNA fragment containing a translation start signal can be inserted between the promoter and truncated lacZ gene to produce a hybrid protein with functional beta galactosidase activity. The vectors described here differ in sequence between the EcoRI cloning site and the lacZ gene to allow easy, in-frame joining of DNA containing a translation initiation signal to the lacZ gene. Cells containing plasmids can be screened directly for in-frame inserts by colony color on indicator plates. PMID- 3091458 TI - [Use of the method of liver perfusion in the study of the toxic properties of thiourea]. PMID- 3091459 TI - Comparison of unfractionated heparin and low molecular weight heparin during long term use in chronic haemodialysis and haemofiltration patients. AB - Antithrombotic activity, necessary doses and effects on coagulation and lipid variables of the low molecular weight heparin derivative Fragmin were compared to unfractionated (UF) heparin in long-term multicentre trials. Results of more than 10,000 dialyses are reported. On the basis of preliminary studies, UF heparin and Fragmin doses were used that lead to anti-Xa activities of more than 0.5 U/ml. With this dose, sufficient antithrombotic activity was achieved with both heparins. Bleeding complications were not noticed. Partial thromboplastin time (PTT) and thrombin time were only marginally increased by Fragmin (5-8 s) in contrast to UF heparin (PTT 90-120 s, thrombin time 230-260 s). Surprisingly, the elevated levels of factor VIII strongly decreased during the 6-month treatment period with Fragmin and increased again during the following 6-month treatment period with UF heparin. Creatinine, urea, haemoglobin and transaminases did not change in both heparin groups: this excluded reduced dialysis efficiency or occult blood loss. Additionally, 15 patients with acute renal failure and high bleeding risk were dialysed with low doses of Fragmin (anti-FXa: 0.2-0.3 U/ml). No severe bleeding occurred. A continuous ambulant peritoneal dialysis patient with deep vein thrombosis was treated effectively with intraperitoneal application of Fragmin for 6 months without any problems. PMID- 3091460 TI - [Replacement therapy with intravenous gamimune serum]. PMID- 3091461 TI - External fixation arthrodesis of the ankle joint following trauma. AB - Arthrodesis is currently the treatment of choice for symptomatic degenerative arthropathy of the ankle. Thirty-seven patients underwent arthrodesis for post traumatic disorders using either a Hoffmann external fixator or a Calandruccio frame. There was degenerative joint disease in 19 (51%), septic arthritis in 11 (30%), severe comminution in five (14%), and uncontrollable equinus in two (5%). The patients were divided into two groups. Twenty-six (70%) were considered to have sustained high energy open or comminuted injuries and 11 (30%), low energy injuries. Twenty-nine (78%) achieved a radiologic fusion following one operation. Four eventually united with further surgery for a final arthrodesis rate of 89%. In the high energy group 18 of 26 (69%) achieved primary fusion. Four united with additional surgery for a final arthrodesis rate of 85%. Two of these required subsequent amputations and two others, a triple arthrodesis which also failed to control chronic pain. Thus, a total of 18 of the 26 patients (69%) achieved a successful result. Also included in the high energy group were three patients with uncontrolled sepsis who underwent amputation before union occurred and one with a painful non-union. All 11 of the patients (100%) who originally sustained low energy injuries achieved a successful arthrodesis. The most common complication was in pin tract infection requiring incision, drainage, and oral antibiotics in 16 patients (43%). None of these progressed to chronic osteomyelitis. PMID- 3091462 TI - Quantitative IgD measurement for discrimination of human bloodstains. AB - The IgD concentrations of eluates of artificial bloodstains and of the corresponding sera from 40 subjects of different ages were measured by single radial immunodiffusion. IgD was found in bloodstains stored up to 53 days, i.e. IgD storage stability is sufficient for forensic purposes. Since serum IgD concentrations of individuals, in particular of adults, are almost invariable and serum levels of different individuals can vary by more than a 1000-fold, the discrimination of bloodstains on the basis of IgD is generally possible. Thus IgD constitutes a further marker in antibody profiling of bloodstains. PMID- 3091463 TI - [Eye changes in partial trisomy 4p]. PMID- 3091464 TI - America's hospitals: what's right and what could be better? PMID- 3091465 TI - The case for adjusting hospital death rates for severity of illness. PMID- 3091466 TI - Lessons of the New Jersey DRG payment system. PMID- 3091467 TI - Effects of proximal gastric vagotomy on gastric secretory and plasma hormonal responses to sham feeding in patients with duodenal ulcers. AB - The effects of proximal gastric vagotomy on the gastric secretion of acid and pepsin, and on the release of gastrin and pancreatic polypeptide in response to sham feeding were assessed comparatively within 1-4 months after surgery in 32 male duodenal ulcer patients. Each test comprised three successive periods: basal, modified sham feeding (MSF) and pentagastrin stimulation. In each test period the acid output was strongly correlated with the corresponding pepsin output, both parameters being reduced to similar extents after vagotomy. The percentage of postoperative reduction of MSF-induced acid and pepsin outputs was positively correlated with the preoperative values. MSF resulted in a limited but significant release of gastrin, the response being significantly greater after surgery. The MSF-induced release of pancreatic polypeptide was significantly reduced by proximal gastric vagotomy, the reduction percentage being negatively correlated with the time elapsed since surgery. Neither pre- nor post-operatively did the gastrin and pancreatic polypeptide responses bear any relationship to the other parameters tested. We conclude that the study of sham feeding responses of pepsin, gastrin and pancreatic polypeptide provides no further information than does the measurement of acid secretion for the segregation of duodenal ulcer patients, especially with respect to follow-ups for ulcer recurrence. PMID- 3091468 TI - The effects of rioprostil on gastric emptying and intragastric acidity. AB - Rioprostil is a 16-methyl-16-hydroxy alcohol analogue of prostaglandin E1 with anti-secretory activity. We have compared the effects of the orally administered drug with those of placebo and of intravenous ranitidine on the rate of gastric emptying of liquids and on the disposal of acid in the stomach, by measuring the response to an intragastrically instilled acid load in 10 healthy male volunteers. The results show that rioprostil significantly increases the rate of gastric emptying compared with placebo and also significantly reduces the recovery of acid from the stomach. Reduction in the amount of intragastric acid was also observed after intravenous administration of ranitidine but the latter drug did not influence the rate of gastric emptying. We conclude that rioprostil, like ranitidine, reduces the amount of acid in the gastric lumen mainly by inhibiting the gastric secretory response to the instilled acid load, while the action of rioprostil on gastric emptying is independent of its gastric antisecretory properties. The combination of pharmacological actions--increasing the rate of gastric emptying of liquids and inhibiting gastric secretion of acid- indicates that rioprostil may be of value in the management of gastro-oesophageal reflux. PMID- 3091469 TI - Psychosomatic factors and peptic ulcer disease. AB - The authors present a review of the role of psychological factors in peptic ulcer disease (PU). Three lines of research have been identified: personality, psychological factors and PU; stressful life events and their relationship to PU; possible interactions between biological parameters, the CNS and psychosocial aspects. The analysis of the studies presented shows that there is a certain level of agreement with regard to personality and psychological aspects; PU patients present a personality with dependence/independence problems and high level of anxiety. Data concerning the role of stress appear to be far from uniform and often even contradictory. Much remains to be done with respect to the possible links between psychological and biological parameters; there have been only few studies in man--which have not been duplicated and were performed on a limited number of patients--but a fair number in animals. However, the results concerning the relationship between psyche and secretory patterns are very interesting, and represent one of the most important lines of future research. PMID- 3091470 TI - Low incidence of post-transfusion hepatitis in patients with liver cirrhosis. AB - A study has been undertaken to determine the incidence of post-transfusion hepatitis in 57 patients with liver cirrhosis (non-B type) and 93 cases without liver disease, who received blood transfusion during major surgery. A significantly lower incidence of post-transfusion hepatitis (5.3%) was found in patients with liver cirrhosis than in those (17.2%) without liver disease. Two out of three cirrhotic patients with post-transfusion hepatitis progressed to the clinical state of hepatic failure. PMID- 3091471 TI - [Effect of tetracyclines on protein metabolism in cultured hepatocytes]. AB - The purpose of the present study was to investigate the effect of Tetracyclines (TCs); Minocycline (MINO), Tetracycline (TC), Demethylchlortetracycline (DMTC), Pyrrolidinomethyltetracycline (PMTC), on amino acid transport and incorporation in hepatocytes. By the use of liver cell culture, this study was done without complex interactions taking place in whole animals. MINO inhibited most strongly both uptake and incorporation into cellular protein of 3H-L-leucine in cultures of a clonal strain of rat hepatoma cells. This inhibitory effect of MINO was proved to be dose-dependent and reversible. The order of the inhibitory effect of TCs was follows; MINO, DMTC, TC, PMTC. But this inhibitory effect showed no significant correlation with the intracellular content of TCs. Almost the same degree as the inhibition by TCs of 3H-L-leucine incorporation into protein was noted when measuring total intracellular 3H-L-leucine reduction by TCs. These results suggest that the TCs-induced liver dysfunction is probably due to the inhibitory effect of TCs on amino acids uptake followed by inhibition of protein synthesis. PMID- 3091472 TI - Time-dependent effects of oral thyrotropin-releasing hormone in hyperthyroid female rats. AB - We have studied the thyrotropin (TSH) and thyroid hormone (T3) response to acute thyrotropin-releasing hormone (TRH) administration in rats previously rendered hyperthyroid by daily ip injection of 25 micrograms L-T4/100 g bw for 30 days. Animals were thereafter put on distilled water or TRH (2 mg/10 ml) as drinking solution for another 18 days, continuing T4 administration. On days 3 and 10 on oral TRH, the serum TSH and T3 response to TRH was studied by administering 2 micrograms of the tripeptide iv. After 3 days, neither the animals on oral DW, nor those on oral TRH showed any response. Nevertheless, after 10 days, animals on oral TRH had a measurable, significant thyrotropin response. At sacrifice (18 days), animals on oral TRH had increased pituitary TSH content. These results confirm and extend a recent report from our laboratory (Iglesias, Llobera and Montoya 1985). We conclude that TRH-mediated thyrotropin accumulation in pituitary is the primary cause for the presence of this response. PMID- 3091473 TI - Catecholamines and pituitary-function. V. Effect of low-dose dopamine infusion on basal and gonadotropin-releasing hormone stimulated gonadotropin release in normal cycling women and patients with hyperprolactinemic amenorrhea. AB - To verify the role of dopaminergic mechanisms in the control of gonadotropin secretion in normal and hyperprolactinemic women, we examined the gonadotropin response to GnRH (100 micrograms i.v.) administration in both basal conditions and during low-dose dopamine (DA, 0.1 microgram/kg/min) infusion. Hyperprolactinemic women, either with microadenoma or without radiological signs of pituitary tumor, showed significantly enhanced LH and FSH responses to GnRH in comparison with normal cycling women. 0.1 microgram/kg/min DA infusion did not result in any appreciable suppression of serum gonadotropin levels but significantly reduced the LH and FSH responses to GnRH in both normal and amenorrheic hyperprolactinemic women. Although both LH and FSH levels remained higher in hyperprolactinemic patients than in normal women after GnRH, the gonadotroph's sensitivity to DA inhibition was normal in the hyperprolactinemic group, as both control subjects and patients with hyperprolactinemic showed similar per cent suppression of GnRH-stimulated gonadotropin release during DA. These data confirm that hypothalamic DA modulates the gonadotroph's responsiveness to GnRH. The increased LH and FSH responses to GnRH in hyperprolactinemic patients and their reduction during low-dose DA infusion seem to indicate that endogenous DA inhibition of pituitary gonadotropin release is reduced rather than enhanced in women with pathological hyperprolactinemia. PMID- 3091474 TI - Gastric signet-ring cell lymphoma with alpha heavy chains. AB - Signet-ring cell lymphomas are rare especially as primary gastric tumours; alpha chain disease of the stomach is also unusual. A case of gastric signet-ring cell lymphoma with free alpha chains in the gastro-duodenal juice is reported and its light microscopic, immunohistological and ultrastructural features are described. Although the morphogenesis of signet-ring cell lymphoma is not clear, the present case showed many of the features of a mucosa-associated lymphoma. This rare variant of follicle centre cell lymphoma may easily be mistaken for a signet-ring cell carcinoma. A search for abnormal immunoglobulins should be made in serum, secretions or tissues in future cases of signet-ring cell lymphoma. PMID- 3091475 TI - Plexiform tumorlet of the uterus: immunohistological evidence for a smooth muscle origin. AB - A case of plexiform tumorlet of the uterus is reported and studied histologically and by immunohistochemistry. The presence of desmin in the tumour cells demonstrates their smooth muscle origin. These results are compared with other reports in the literature with special emphasis on histogenesis. PMID- 3091476 TI - Biologic effects of gamma interferon pre-treatment followed by monoclonal antibody 17-1A administration in patients with gastrointestinal carcinoma. AB - Twenty-seven patients with metastatic adenocarcinoma of the colon or pancreas were treated with 400mg of monoclonal antibody 17-1A. This antibody, which binds to a cell surface glycoprotein moiety preferentially expressed by adenocarcinomas of the rectum, colon, pancreas, and stomach, is postulated to induce antibody dependent monocyte cytotoxicity (ADMC) as a mechanism of tumor lysis. Therapy was preceded by four days of gamma interferon infusions, with the intent of activating peripheral blood monocytes, enhancing monocyte Fc receptor expression and increasing the likelihood of tumor lysis as reflected by enhanced ADMC directed against a colon carcinoma cell line (SW1116) which expresses 17-1A's target antigen. In this Phase I study patients were treated daily at one of the following gamma interferon dose levels (X 10(6) U/M2/day): 0.001, 0.01, 0.1, 1.0, 10.0, 40.0, 60.0, 80.0. Addition of 100 U/ml of rIFN-gamma in vitro to monocytes isolated from normal controls or from patients prior to treatment significantly enhanced monocyte Fc receptor expression and ADMC. in vitro tumor cell killing by monocytes and monoclonal antibody was enhanced by treatment with low doses of rIFN-gamma, while treatment with high doses of rIFN-gamma did not enhance ADMC. No objective clinical responses were noted, although serum tumor markers dropped transiently in 36% of the treated patients. Seven of 11 assayed patients developed human anti-idiotype antibodies. With better scheduling of rIFN- and 17 1A we hope to duplicate optimal in vitro conditions for antibody-mediated cytotoxicity, hopefully enhancing in vivo antibody mediated tumor lysis. PMID- 3091477 TI - A universal and inexpensive servomotor for vestibular research. PMID- 3091478 TI - IL2: receptors and genes. PMID- 3091479 TI - Structure and function of the interleukin 2 receptor: affinity conversion model. AB - We cloned cDNAs of the human and mouse IL-2 receptors. Comparison of their structures allowed us to identify several conserved regions localized to exons 2 and 4, the cytoplasmic portion and the transmembrane portion. These regions might be important for the functions of the IL-2 receptor. The human IL-2 receptor, which was expressed on an IL-2-dependent murine T-cell line, CTLL-2, by cDNA transfection, was shown to be functionally active by blocking the endogenous mouse IL-2 receptor with monoclonal antibodies. On the other hand, the human IL-2 receptors expressed on non-lymphoid cells were functionally inactive. They were unable to mediate the growth signal, were of low affinity species and aberrant in internalization. We postulated that the dysfunction of the IL-2 receptors in non lymphoid cells would be due to the absence of the putative converter protein which is expressed specifically in lymphoid cells. Since the human IL-2 receptor is active in the murine T cell, the converter may interact with the receptor at the portions conserved between man and mouse. We proposed the affinity conversion model that explained the high affinity state of the receptor by the ternary complex formation between IL-2, the IL-2 receptor and the converter. PMID- 3091480 TI - Molecular analysis of the interleukin-2 system. PMID- 3091481 TI - The human interleukin-2 receptor: analysis of structure and function. AB - Considerable information presently exists regarding the molecular, biochemical, and biological features of the human IL-2 receptor. The IL-2 receptor protein, multiple receptor mRNAs, and a single structural gene have now been identified. The important role of this receptor in normal T-cell growth is well established and its potential participation in B-cell growth and differentiation appreciated. The availability of cloned gene products for both the IL-2 receptor and IL-2 may permit the future development of novel biological agents capable of either augmenting or blunting the T-cell immune response. The intriguing interrelationship of HTLV-I and -II infection and altered IL-2 receptor expression is now being unraveled. However, the structural difference in high and low affinity receptors as well as the mechanism by which signals for T-cell growth are propagated through the high affinity receptor remain dominant, unanswered questions in the field. PMID- 3091483 TI - The interleukin-2 receptor, its physiology and a new approach to a selective immunosuppressive therapy by anti-interleukin-2 receptor monoclonal antibodies. AB - In this report we have summarized our findings on the IL-2 receptor and our attempts to find an IL-2 receptor targeted immunosuppressive therapy. IL-2 receptors are detectable in two different forms: as monomeric, surface expressed, and as dimeric, presumably non-surface expressed molecules. The dimeric form seems to be non-covalently bound to an as yet undefined 110 KD molecule. The functions of the monomeric versus the dimeric form, as well as that of the noncovalently bound molecule, and their relationship to high and low affinity IL 2 receptors are not yet clear and remain to be elucidated. Upon antigenic or mitogenic stimulation, IL-2 receptors became expressed at the surface of T lymphocytes. Receptor expression is accompanied by the capacity of the cells to proliferate in response to IL-2. Resting T-cells do not proliferate in response to IL-2. IL-2 dependent proliferation of cells without external stimulation is either due to the presence of a small number of IL-2 receptor bearing cells in the respective population or due to a small number of IL-2 receptors present on the surface of cells. IL-2 itself does not induce IL-2 receptor expression on resting cells but has been shown to up-regulate its own receptor once expressed. In contrast to resting lymphocytes, some leukemic cells and early embryonic thymocytes in the species tested constitutively express IL-2 receptors. The role of such constitutively expressed receptors is not yet clear. As demonstrated in mice, the requirement(s) for induction of IL-2 receptor expression for the helper/inducer subset (Lyt-2+) are different from those of the cytotoxic/suppressor subset (L3T4+). In contrast to Lyt-2+ cells, the accessory cell requirement for L3T4+ cells could not be replaced by cytokines. Whether Lyt 2+ cells require an additional, not yet defined receptor inducing factor (RIF) besides IL-2 in order to become IL-2 receptor positive and to consequently proliferate in response to IL-2, is a matter of controversy. There is evidence that interleukin-1 and some functionally related factors produced by leukemic cells enhance expression and/or function of the IL-2 receptors. IL-2 receptors of the high and low affinity type expressed upon antigenic stimulation are cleared from the cell surface. As demonstrated in this report, the vast majority of them, probably those of low affinity type, are released from the cells continuously. The mechanism of their release and the possible immunoregulatory role of circulating receptors found in the serum of animals is not yet clear.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3091482 TI - Biochemical and molecular events associated with interleukin 2 regulation of lymphocyte proliferation. PMID- 3091484 TI - IL 2 receptor expression on differentiating lymphocytes in the murine thymocyte. PMID- 3091485 TI - The murine interleukin-2 receptor: biochemical structure and regulation of expression. PMID- 3091486 TI - In vivo activation of macrophages by T cell-derived lymphokines: killing of tumor cells and schistosomula of Schistosoma mansoni. AB - We investigated the role of T cell-derived lymphokines for macrophage activation in vivo. We show for the first time that macrophages from casein-pretreated mice can be primed in vivo by intraperitoneal injection of immune interferon (IFN gamma) and can be triggered by lipopolysaccharide (LPS) in vitro to kill schistosomula of S. mansoni. Similar results were obtained for the activation of tumoricidal macrophages. Injection of casein-pretreated mice with concanavalin A (Con A)-induced supernatant of a long-term T cell clone containing IFN-gamma and macrophage cytotoxicity inducing factor 2 (MCIF2), however, induced macrophage activation in vivo without further addition of LPS in vitro. These experiments show that macrophages can be activated by lymphokines in vivo. In addition, the data suggest that a combination of IFN-gamma with MCIF2 might be more effective than IFN-gamma alone. These data may be relevant for the strategy of treating cancer and infectious diseases with lymphokines. PMID- 3091487 TI - Mechanism whereby ouabain inhibits human T lymphocyte activation: effect on the interleukin 2 pathway. AB - Through the blockade of the Na-K-ATPase, ouabain inhibits several biochemical and biological events leading to the proliferation of activated lymphocytes. Since we already found that interleukin 1 production was not prevented by ouabain, we investigated by which mechanism this drug inhibits mitogen-induced human T lymphocyte activation, with respect to the interleukin 2 (IL 2) pathway. Our data revealed that at concentrations lower than 0.2 microM, IL 2 accumulation was not reduced in ouabain-treated cultures, even when cell proliferation was completely inhibited (0.1-0.2 microM ouabain). Moreover, in this concentration range, ouabain stimulated in a dose-dependent manner the accumulation of IL 2 in the supernatant of Con A-stimulated lymphocytes (optimum for 0.05 microM corresponding to half inhibition of lymphocyte proliferation). Such an effect, which appears correlated to the inhibition of Na-K-ATPase, suggests a failure of the cell to utilize IL 2. At concentrations higher than 0.3 microM, ouabain inhibited both lymphocyte proliferation and IL 2 production. These observations show that the glycosteroid interacts differently with the different cell populations involved in the cascade of reactions leading to cell proliferation, and suggest that the mitogenic inhibition resulting from the blockade of Na-K ATPase is not related to the blockade of IL 2 production. On the other hand, we observed that: ouabain inhibited the expression of the receptors for IL 2, an obligatory step in lymphocyte proliferation; ouabain blocked the proliferation of an IL 2 sensitive human T cell line; in both cases the inhibition paralleled that of lymphocyte proliferation. Our data suggest that the essential steps of lymphocyte proliferation in which Na-K-ATPase-dependent K+ fluxes play a critical role are the expression of IL 2 receptors and the IL 2-dependent proliferative step. PMID- 3091488 TI - Role of IFN-gamma and alpha in IL 1 synthesis and secretion of in vitro differentiated human macrophages: a comparative study. AB - Human blood monocytes (Mo) cultured in vitro differentiate to macrophages (Mx) and lose the capacity to secrete interleukin 1 (IL 1) in response to endotoxin (LPS). Incubation of Mo with interferon gamma or alpha (IFN-gamma or IFN-alpha) prevented this loss of IL 1 secretory potential during the first 24 h of culture. However, there were marked differences between the two interferons if culture period was extended beyond 24 h. Incubation of Mo with IFN-gamma for 48 or 72 h induced IL 1 release in response to LPS in all the donors without exception. In contrast, 48-h incubation of Mo with IFN-alpha alpha caused IL 1 secretion (in response to LPS) in only a minority of donors, while 72-h incubation resulted in very little or no IL 1 release in all the individuals tested. Moreover, only IFN gamma had the capacity to reinduce IL 1 secretory potential in Mx which had lost the capacity to secrete IL 1 during previous culture. These and other results suggest that IFN-alpha differs from IFN-gamma in being: a less potent IL 1 inducer, ineffective in maintaining IL 1 secretory capacity of fresh Mo for more than 48-72 h, completely unable to reinduce IL 1 secretory potential in culture derived Mx. Thus, the two species of IFN appear to have a markedly different role in IL 1 synthesis and secretion. PMID- 3091489 TI - Does stem cell self renewal and progenitor cell commitment operate through an effector-memory cell mechanism? AB - We propose a model for stem cell self renewal and transition into commitment towards a variety of cell lineages. In this model the production of both "effector cells" (as represented by the mature cells in the different cell lineages) and of progenitor "memory" lymphocytes, takes place concomitantly. The experimental evidence supporting this model is as follows: Pure lymphocytic suspensions (PLS) are established and persist in culture when nude mouse-spleen and lymph-node cells are maintained on X-irradiated fibroblast monolayers in the presence of the S-phase cytotoxic agent cytosine arabinoside (Ara-C). From these PLS the following colony types can be initiated by the corresponding inducing (stimulating) factors (CSF): histiocytes (tissue macrophages) - CSF-1; granulocytes-macrophages (GM) - CSF-GM; mast cells - MMSF; granular-NK mucus secreting cells - IL-2; and multilineage colonies - IL-3. Mitotically active blast cells (formed by transformation of lymphocytes), condense into motile small cells when the stimulatory factor is removed. These "memory" lymphocytes are committed as they carry the receptors for the specific CSF; they respond by retransformation into blast cells. A dramatic increase in mast-cell colony forming cells is found in bone marrow, spleen and lymph-nodes of mice infected with Schistosoma mansoni. By maintaining PLS with both Ara-C and each of the CSFs and then titrating the incidence of CFC in the residual PLS, we find that each one of the CSFs acts on an independent set of cells in the PLS to produce the corresponding colony type. Finally, the concept suggests that the various blast cells carrying the receptors, undergo condensation into memory lymphocytes when dissociated from the environment prevailed by the corresponding CSF. In this way pluripotential blast-cells condense into motile lymphocytes which are committed to pluripotentiality. PMID- 3091490 TI - Establishment of human cell lines producing anti-D monoclonal antibodies: identification of Rhesus D antigen. AB - Two cell lines producing monoclonal antibodies have been established from peripheral blood of a negative Rhesus blood donor which has been immunized with positive Rhesus red blood cells. Two monoclonal antibodies Co II 8.8 and Co II 7.12 have been selected. Both are IgG1 antibodies, but recognize different epitopes on the Rhesus D antigen, apparently associated with different subunits of the D antigen. Thus the Co II 8.8, like the positive serum, immunoprecipitates an antigen of a relative molecular weight of 33 kDa, while the Co II 7.12 recognizes an antigen of Mr 42 kDa. PMID- 3091491 TI - The genetic control of syngeneic delayed-type hypersensitivity (syn-DTH). PMID- 3091492 TI - Coagulum choledocholithotomy: a preliminary report. PMID- 3091494 TI - Mucopolysaccharidoses in Calcutta. PMID- 3091493 TI - Nutrition and drug disposition. PMID- 3091495 TI - Correlation between mouse skin inflammation induced by arachidonic acid and eicosanoid synthesis. AB - We and others have shown that arachidonic acid (AA), when applied topically to ear surfaces, causes an intense acute inflammatory reaction within minutes (as measured by ear thickness). In this study, we have investigated the cellular and biochemical changes associated with this phenomenon and have attempted to correlate these changes with the induction of inflammation. Measurement of vascular permeability by the accumulation of [125I]albumin showed that significant plasma exudation was observed at 15 min in AA-treated ears. Furthermore, the increase in [125I]albumin was time related and was nearly 10 fold greater than control at 1 h. No time-related change in plasma exudation was observed with control ears. Measurement of LTC4 by radioimmunoassay showed that there was a significant increase in LTC4 synthesis at 15 min after AA treatment. Maximal LTC4 synthesis occurred at 15 min and subsequently decreased to 30% of peak level at 30 min. Histological examination and myeloperoxidase measurement indicated that few neutrophils were present at these early time points and suggested that cells other than neutrophils are contributing to LTC4 synthesis. Ear thickness, [125I]albumin accumulation and leukotriene C4 (LTC4) synthesis in AA-treated ears were reduced significantly by topically administered mixed lipoxygenase (LO) and cyclooxygenase inhibitors such as BW755C and phenidone. Therefore, we suggest that AA-induced ear inflammation is a suitable screen for detecting LO inhibitors in vivo. PMID- 3091496 TI - Role of extracellular calcium in neutrophil responsiveness to chemotactic tripeptides. AB - Cellular stores of Ca2+, but not extracellular Ca2+, are required for effective FMLP stimulation of neutrophil O2- production and degranulation. Neutrophils transferred from Ca2+-containing to Ca2+-free medium gradually lose their responsiveness to FMLP, such that after 40 min in the Ca2+-free environment they have lost 60-70% of their initial responsiveness to FMLP. The loss in responsiveness is reflected both in an increase in lag interval and decrease in velocity of O2-synthesis. The rate of decline in responsiveness to FMLP is greatly accelerated when neutrophils incubated in the presence of A23187 and Ca2+ free medium, while the rate of loss of responsiveness to FMLP is not affected by EGTA but the extent of loss is increased. Gradual recovery of FMLP-induced O2- generation occurs when cells are transferred from Ca2+-free to Ca2+-containing medium. PMA-induced neutrophil O2- generation is not influenced by the presence or absence of extracellular Ca2+. It is our view that the rise or fall of neutrophil responsiveness reflects repletion or depletion of cellular stores of Ca2+ essential for stimulus-effector coupling and that the role of extracellular Ca2+ is subservient to maintenance of these stores. PMID- 3091497 TI - Leucocyte free amino acid alterations in hypoproteinemic conditions. PMID- 3091498 TI - Malnutrition and immune system. PMID- 3091499 TI - [Adjuvant parenteral nutrition in cytostatic chemotherapy]. AB - Adjuvant parenteral nutrition of tumor patients receiving cytotoxic chemotherapy offers many potential advantages. There are some randomized studies with few cases looking at the effect of parenteral nutrition on tumor response and toxicity. In an own prospective randomized study on parenteral nutrition of colorectal cancer patients an increase of tumor response, prolongation of survival, or reduction of toxicity could not be achieved. Published controlled studies are discussed in a literature review. Parenteral nutrition of tumor patients receiving chemotherapy is not principally advantageous and should be restricted to special clinical situations. PMID- 3091500 TI - [Adjuvant parenteral nutrition in chemo- and radiotherapeutic measures in hematology]. AB - The study investigates clinical nutrition of oncological patients as an essential adjuvant component in the whole therapeutical concept. The main subject of the study was the transfer of nutritional concepts which were developed in non malignant diseases to oncological patients. We defined the homeostasis of patients by biochemical and biophysical parameters in blood (osmolality, Na, K, total protein, albumin, triglycerides, NEFA, glucose, lactate, creatinine, urea, total nitrogen, amino acids) and urine (volume, osmolality, Na, K, creatinine, urea, total nitrogen, and amino acids). Of special interest was the homeostasis of nitrogen, which was characterized by the loss of nitrogen and nitrogen balances. 10 patients with either transplantable panmyeolopathy or leukemia were investigated including a phase of immunsupressive treatment by total body radiation and cytostatic treatment. Parenteral nutrition was made with amino acids (1 g/kg/d), carbohydrates (6.5 g/kg/d) and fat (1 g/kg/d). During the preparatory phase nutrition was interrupted for two consecutive days because high amounts of electrolyte solution with up to 6 1/day were needed to protect the kidney. The period of investigation covered the complete period of treatment which endured up to three months. The essential result was the achievement of a constant body weight which decreased drastically under the conventional treatment without optimized nutrition. The homeostasis remained unchanged inspite of the fact that great changes occurred individually. Nitrogen balance and nitrogen loss demonstrate the strong influence of immun-suppresive treatment with N-losses of up to 20 g per day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091501 TI - [Possibilities for the use of formula diets for tumor patients]. AB - Malnutrition is a frequent problem in cancer patients. Nearly 50% of all tumor patients lose more than 10% of their pre-illness weight during the various stages of their disease. Ingestion-dependent abdominal pain in patients with gastrointestinal tumor complications is a major problem among the causes which are under discussion. Elemental diet has a safe analgetic effect in these patients because of its quick and complete resorption in proximal parts oft the jejunum. Tube feeding with elemental diets can be provided fully ambulatory and leads to a significant increase in the quality of life of cancer patients. This was demonstrated in a group of 38 malnourished cancer patients. The effect of tube feeding combined with chemotherapy was investigated in a small group of 10 patients with low Karnofsky index. The outcome was compared to the results of 9 international chemotherapy studies using the same chemotherapeutic regime without artificial feeding. PMID- 3091502 TI - [Clinical study of the bacterial contamination of 2 differently prepared enteral feeding solutions]. AB - The incidence of bacterial contamination under ICU-conditions of two solutions designed for enteral feeding; the oligopeptide mixture Peptisorb and the nutrient defined diet Biosorb, were investigated. 54% of the specimens taken prior to use from the oligopeptide mixture, which is marketed as a powder and brought into solution before application, were found to be bacterially contaminated. At the end of the 6-12 h application period this percentage has risen to 79%. Prior to use the sterile packed prepared nutrient defined diet was found to be free of bacterial contamination in 97% of cases, while at the end of the period of application 21% of the samples taken contained bacteria. In most instances the solutions prepared on ICU were contaminated with gram positive spore forming bacteria and typical gram negative hospital flora. Based on the results of this investigation, only those enteral feeds which are marketed as sterile solutions should be used, in order to protect ICU patients from potential sources of contamination. PMID- 3091503 TI - Isolation of a coccidioidin component that reacts with immunoglobulin M precipitin antibody. AB - Detection of immunoglobulin M (IgM) precipitin antibody to coccidioidin, the autolysate of mycelial-phase cells of Coccidioides immitis, is an important serologic aid in establishing a diagnosis of primary coccidioidomycosis. In the present study, the component of coccidioidin that reacts with IgM precipitin antibody was isolated by a combination of immunoaffinity and anion-exchange chromatography. Antigenic analysis of the purified antigen in two-dimensional immunoelectrophoresis against goat anti-coccidioidin revealed a precipitinogen characterized by a complete cathodal leg and a partial anodal leg. The reactivity of this incomplete precipitating antigen with anti-C. immitis IgM was established by serologic assays and by the adsorption of reference IgM precipitin antibody on solid-phase immunosorbents containing the purified precipitinogen. The isolation of the coccidioidin component that reacts with IgM precipitin antibody and the production of monospecific antibody will provide the necessary reagents for the development of a sensitive immunoassay for detecting this serodiagnostic response. PMID- 3091504 TI - Factors affecting the multiplication and subculture of Treponema pallidum subsp. pallidum in a tissue culture system. AB - Limited multiplication of Treponema pallidum subsp. pallidum (Nichols strain) can be obtained in the presence of Sf1Ep rabbit epithelial cell cultures, but continuous culture has not yet been achieved. In the system currently employed, growth is exponential for the first 10 to 15 days of culturing, after which multiplication and the percentage of motile organisms decrease. In an effort to identify culture conditions which may adversely affect treponemal viability and growth, eight culture parameters were monitored over a 12-day period of incubation. Several of these parameters, including pH, redox potential, dissolved oxygen concentration, and glucose levels were found to change dramatically during the course of incubation, indicating that they may be responsible for the cessation of treponemal multiplication. The feasibility of extending the period of growth by subculturing was also investigated. In preparation for planned serial subcultivation experiments, several subculture procedures were tested and found to be effective in allowing the transfer of T. pallidum from 3-day-old primary cultures to secondary cultures without loss of motility or growth potential. Increases of up to 55-fold were observed in secondary cultures, but increased growth due to subculturing was not a consistent finding. Use of subculture intervals of greater than or equal to 6 days resulted in a progressive decrease in treponemal multiplication in secondary cultures, although retention of motility was extended in the subcultures compared with motility in the primary cultures. These results indicate that the lack of continued multiplication of T. pallidum in subcultures is not due to damage to the treponemes during subculture. Prolonged multiplication of T. pallidum may be obtained through the stabilization of culture conditions by either performing subcultures at regular intervals or by medium replacement techniques. It was also found that primary T. pallidum cultures could be established by using as the inoculum treponemes that had been stored at -70 degrees C in a medium containing 15% glycerol. PMID- 3091505 TI - T-cell-independent macrophage activation in mice induced with rRNA from Listeria monocytogenes and dimethyldioctadecylammonium bromide. AB - Purified rRNA from Listeria monocytogenes or Pseudomonas aeruginosa injected in combination with dimethyldioctadecylammonium bromide (DDA), protects mice nonspecifically against a lethal challenge of various extra- and intracellular bacteria. In the present study vaccination of BALB/c as well as C57BL/Ka mice with listerial RNA-DDA resulted in activation of fixed-tissue macrophages, as measured by an enhanced in vivo L. monocytogenes killing in spleen and liver. Evidence was found that macrophage activation by vaccination with rRNA-DDA occurred by a T-cell-independent mechanism. Treatment of mice with cyclosporin A had no effect on the enhanced L. monocytogenes killing induced with RNA-DDA; in vitro exposure of RNA-DDA to spleen cell cultures did not give rise to any lymphocyte proliferation. No evidence could be found for a possible adjuvant activity for RNA-DDA in cellular responses; in fact, RNA-DDA had an inhibitory effect on lymphocyte proliferative responses to Listeria antigen and to concanavalin A. PMID- 3091506 TI - Monoclonal antibodies to Pseudomonas aeruginosa ferripyochelin-binding protein. AB - Hybridomas secreting specific monoclonal antibodies against the Pseudomonas aeruginosa ferripyochelin-binding protein (FBP) were isolated. These monoclonal antibodies reacted with FBP in immunoblots of outer membrane preparations from all serotypes of P. aeruginosa. Two of the monoclonal antibodies also reacted with FBP in strains of P. putida, P. fluorescens, and P. stutzeri. These antibodies did not react with outer membranes of P. cepacia, "P. multivorans," P. maltophilia, or other gram-negative organisms. The monoclonal antibodies were opsonophagocytic and blocked the binding of [59Fe]ferripyochelin to isolated outer membranes of strain PAO. By indirect immunofluorescence techniques, the monoclonal antibodies were used to demonstrate that FBP is present on the cell surface of P. aeruginosa cells grown in low-iron but not high-iron medium. These observations were confirmed by using 125I in surface-labeling techniques. PMID- 3091507 TI - Recombinant human gamma interferon inhibits simian malaria. AB - Prophylactic treatment with 0.1 mg of human gamma interferon per kg (body weight) per day completely suppressed experimental infection with Plasmodium cynomolgi B sporozoites in rhesus monkeys. Treatment with lower doses partially suppressed this infection. Prophylactic treatment with human gamma interferon, however, had no protective effect against trophozoite-induced infection, suggesting that the interferon effect was limited to the exoerythrocytic stage of parasitic development. PMID- 3091508 TI - An established MRL/Mp-lpr/lpr cell line with null cell properties produces a B cell differentiation factor(s) that promotes anti-single-stranded DNA antibody production in MRL spleen cell culture. AB - The cell line established from the lymph node cells of an MRL/lpr mouse, was found to have null cell properties in that it lacked Thy-1, Lyt-1 and Lyt-2 as well as sIg, and continued to grow in the absence of exogeneously added lymphokines such as IL-2 and IL-3. Interestingly, this cell line (KML1) or a soluble factor(s) produced by it promoted anti-ssDNA antibody production in cultures of MRL/lpr spleen cells. The factor did not induce cell proliferation. Therefore, it is concluded that the cell line KML1 produced at least a B-cell differentiation factor, but not IL-2 or IL-3 as far as detected with the respective lymphokine-dependent cell lines. PMID- 3091509 TI - UICC project on screening for cancer: report of the workshop on screening for breast cancer. Meeting held in Helsinki, Finland, on April 7-9, 1986. PMID- 3091510 TI - Molecular and immunological evidence of B-cell commitment in "null" acute lymphoblastic leukaemia. AB - The DNA configuration of the immunoglobulin (Ig) heavy and light chain genes and the expression of B-cell-related markers were evaluated in 13 cases of non-T, non B, non-common ("null") acute lymphoblastic leukaemia (ALL). A rearrangement of the Ig heavy-chain gene was found in all cases studied; in 5 of these a structural reorganization of the kappa or lambda light chain gene was also demonstrated. Leukaemic cells from 10 of the 13 cases analysed showed one or more B-cell antigens, the expression of which followed a sequential order of presentation (OKB2, B4, BA-1, B1). The B-cell commitment was confirmed by means of a sensitive immunoperoxidase assay which revealed a weak expression of the common ALL (cALL) antigen in 7/10 cases tested, which were all cALL-negative by conventional immunofluorescence techniques. These findings suggest that in "null" ALL the neoplastic cells show molecular and immunological evidence of B-cell differentiation and that most cases may indeed be characterized by "early" cALL with a very low density expression of the cALL antigen. This was further documented in one case in which the expression of the cALL antigen (and of other B-cell markers) could be induced after exposure to 12-O-tetradecanoylphorbol-13 acetate (TPA). The presence in a few cases of myeloid features, particularly when the cALL antigen could not be demonstrated by the immunoperoxidase assay, suggests that the leukaemic process may sometimes involve a very early progenitor cell capable of both lymphoid and myeloid phenotypic differentiation. The heterogeneity of "null" ALL documented by this study may help to explain the variable clinical course and prognosis of these patients. PMID- 3091511 TI - Identification and localization of urokinase-type plasminogen activator in human NK-cells. AB - We have studied the presence of plasminogen activators in large granular lymphocytes and other peripheral blood cells. After immunofluorescence staining with polyclonal antiserum against urokinase-type plasminogen activator, the majority of LGLs showed granular staining which was located in Golgiderived vesicles. LGLs were negative for tissue-type activator. The presence of only urokinase-type PA in LGLs was also confirmed by determining the molecular weight of the intracellular activator and by immunoblotting the antigen from solubilized cell preparations. Monocytes and granulocytes were more intensely stained with anti-u-PA than LGLs. In LGL/K562 cell conjugates the fluorescence was often located close to the contact area and the vesicular fluorescence polarized during conjugate formation. Inhibitors of PA and other serine proteinases are known to abolish NK-cell activity. We now show that they affect a later stage than programming for lysis in the cytotoxic action, suggesting a role for u-PA or other serine proteases in the lethal-hit stage of NK activity. PMID- 3091512 TI - Differential effects of valproic acid on the serum protein binding of lorazepam and diazepam. AB - Valproic acid and free fatty acids have been shown to displace diazepam from its plasma binding sites both in vitro and in vivo. Since lorazepam exhibits a substantial degree of binding, but differs from other benzodiazepines in that no increase in its free fraction in serum is observed when free fatty acids are raised, the effect of valproate on the serum protein binding of diazepam and lorazepam was assessed. Sodium valproate produced a marked increase in the free fraction of diazepam, but practically no effect on the percentage of free lorazepam. PMID- 3091513 TI - Tegafur chemotherapy for the treatment of gut and liver cancer. AB - Thirteen patients with cancer of the gut, six with hepatocellular carcinoma and three with cancer of the bile duct have been treated with tegafur. All the patients were in an advanced stage of the disease with metastases to lymph-nodes or elsewhere. Each patient was given tegafur (oral daily dose of 600-1200 mg for 15-30 days with a dose-free interval of 25 days). Tegafur with other antiblastic drugs (such as cyclophosphamide, methotrexate, vincristine, doxorubicin, mitomycin) was given to ten patients. The results observed after the first treatment were as follows: partial remission in 14 patients (64%), no change in 4 (18%) and progression of the disease in 4 (18%). Only 10 patients among the 22 who were first treated, underwent one to three subsequent cycles of therapy obtaining with resultant partial remission in four cases, no change in two and progression of the disease in four patients. Side-effects (nausea and vomiting) during the treatment were recorded only in 14% of the patients. No significant impairment of blood functional tests has been documented. A comparison of the results obtained with tegafur and intravenous 5-fluorouracil has been made: the therapeutic effects of these two drugs are similar, but side-effects seem to be less during tegafur treatment. PMID- 3091514 TI - Ossification of the ligamentum flavum of the thoracic spine in adult kyphosis. AB - Ossification of the ligamentum flavum has been recognised as a definite clinical entity as is ossification of the posterior longitudinal ligament. The incidence of both is high in Japan. This study demonstrates that the incidence of ossification of the ligamentum flavum in persons who have a kyphosis of the thoracic or lumbar spine is higher than in those who do not. It is considered that localised mechanical stress affecting the ligamentum flavum is a contributing factor to the development of ossification, together with the generalised factors which may favour bone formation. However, the aetiology of this lesion is still obscure as is that of ossification of the posterior longitudinal ligament. PMID- 3091515 TI - Inhibition of the respiratory burst of human neutrophils by the polyamine oxidase polyamine system. AB - The addition of the polyamines, spermine and spermidine, to human neutrophils caused a depression of the hexose-monophosphate (HMP) shunt activity of neutrophils stimulated with latex particles but not of unstimulated cells. The effect was dependent on the presence of bovine serum and was not observed when normal human serum was substituted for bovine serum. The polyamine oxidase (PAO) in bovine serum was probably responsible for generating the activity since normal human serum lacks PAO. A role for PAO was further supported by the finding that partially purified bovine PAO in the presence of polyamines similarly mediated inhibition of HMP shunt activity in stimulated neutrophils. Catalase failed to prevent the inhibitory effects of the PAO-polyamine system suggesting that H2O2 is not the responsible product. In addition, our results show that human pregnancy serum known to contain PAO activity in the presence of polyamines mediated a similar inhibition of the respiratory burst. PMID- 3091516 TI - Arachidonic acid metabolism in human neutrophils: lack of effect of cyclosporine A. AB - The metabolism of arachidonic acid (AA) in human neutrophils was studied by incorporation of 1-14C-AA, removal of excess 1-14C-AA, and stimulation of radiolabelled cells with A23187. Radiolabelled lipids were quantitated by extraction, thin-layer chromatography, autoradiography, and laser densitometry. Following 5 h of incubation with 1-14C-AA, the maximum amount of radioactivity was located in triglycerides, 70%, and phospholipids, 30%. Activation of the cells with calcium ionophore A23187 led to release of free AA, 58%, whereas AA metabolites revealed mainly lipoxygenase (arachidonate 5 lipoxygenase, E.C. 1. 13. 11. 34) activity, 5-HETE 13%, LTB4 5%, with only small amounts of cyclooxygenase (prostaglandin synthase, E.C. 1. 14. 99. 1) metabolites, HHT 2%. Intra-assay coefficient of variation for release of metabolites was approximately 15%. A potent immunosuppressive agent, cyclosporine A (CS-A) was shown to be without any effect in AA-release and metabolism. This method is applicable to studies of both basic cell function in human disease and to further immunopharmacological investigations. PMID- 3091518 TI - Intraerythrocytic multiplication of Theileria parva in vitro: an ultrastructural study. PMID- 3091517 TI - Juvenile law and the viable fetus: clinical perspectives and legal intervention. PMID- 3091519 TI - Schistosoma mansoni: vaccination with adult worm antigens. PMID- 3091520 TI - Histopathological and parasitological evidence of immunization of mice against challenge with 17 wild isolates of Trypanosoma cruzi. PMID- 3091521 TI - A hypothesis on the primate neocortex evolution: column-multiplication hypothesis. AB - A hypothesis is proposed, that the primate neocortex has evolved by the multiplication of cortical columns. As the column size is similar across primate species, it is considered that the columns have multiplied to expand the neocortex during primate evolution. This hypothesis would explain the expansion of neocortical sensory-motor-associational areas and multiple sensory and motor areas which had occurred during evolution. Further, the hypothesis predicts the existence of columns neutral for the fitness, genetic control upon the columns, and intraspecies variations of the columns. PMID- 3091522 TI - Two modes of analgesic action of aspirin, and the site of analgesic action of salicylic acid. AB - The analgesic activities of aspirin and salicylic acid were investigated by means of the lame-walking test in adjuvant-induced hind-paw-oedematous rats. Aspirin showed ca. 4 times more potent analgesic activity than did salicylic acid in the lame-walking test. The analgesic activity of aspirin was decreased to the level of that of salicylic acid by injection of prostaglandin E2 into the inflamed tissue. The analgesic activity of salicylic acid was not decreased by the same treatment. Salicylic acid inhibited the lame-walking reaction when given intracerebroventricularly. On the other hand, salicylic acid did not inhibit the lame-walking reaction by topical administration on the inflamed hind paw. However, with topical administration, salicylic acid inhibited the carrageenin induced hind-paw oedema. These results suggest that aspirin has two analgesic effects on the inflammatory pain; one may be the inhibition of prostaglandin biosynthesis by acetylation of cyclo-oxygenase, and the other may be an action due to salicylic acid. Salicylic acid may produce its analgesic action mainly via a central mechanism. PMID- 3091523 TI - Bubbling humidifiers produce microaerosols which can carry bacteria. AB - It is widely held that bubbling humidifiers do not produce microaerosols, although prior studies have resulted in conflicting evidence. We have studied this phenomenon in a clean room using an airborne particle counter and samplers for airborne bacteria. At gas flow rates between 10 and 80 L/min, a Cascade 1 humidifier produced between 460 and 999 water droplets/L humidified gas. Total water volume aerosolized was approximately 10(-8) ml/L humidified gas. Seventy three percent of the particles had diameters between 1 and 5 microns. With the reservoir containing 6.4 X 10(6) P. aeruginosa/ml, it produced between 2 and 9 P. aeruginosa/L humidified gas. Most of the bacteria were in particles of a size likely to be deposited in the lung. This bacterial carry-over was between 20 and 150 times the amount predicted by multiplication of the water volume aerosolized times the concentration of bacteria in the humidifier reservoir. An Air Life humidifier produced fewer particles which were also of a size likely to be deposited in the lung and, when the reservoir contained P. aeruginosa, it aerosolized bacteria. Wick-type humidifiers did not produce detectable aerosol or bacterial carry-over. Although the clinical significance of these findings has not been established, they provide a rationale for the CDC recommendations for procedures designed to keep bubbling humidifier reservoir water uncontaminated. PMID- 3091524 TI - An approach for selection of health care personnel handwashing agents. AB - Given the wide range of available health care personnel handwashing agents, selection of an appropriate product may be difficult. This decision may be made on the basis of user preference, cost, or other factors unrelated to product effectiveness. Four criteria--efficacy, safety, cost, and acceptability--are appropriate for systematic evaluation of handwashing products. These criteria are applied to para-chloro-meta-xylenol (PCMX), a compound used with increasing frequency in health care personnel handwashing agents. Published data regarding the biochemical properties, efficacy, and safety of PCMX are summarized. We conclude that the substance appears to be safe and efficacious. However, the activity of PCMX is highly formula-dependent and many of the studies available in scientific literature have been conducted in Europe using a variety of testing conditions and formulations different from those currently available in the US. Clinical studies of marketed formulations are beginning to appear in the literature. Such studies will provide the data needed for adequate product evaluation. PMID- 3091525 TI - [Food allergies]. PMID- 3091526 TI - [A 56-year-old patient with bronchial asthma and massive psoas muscle hematoma]. PMID- 3091527 TI - Immune rejection of metastases arising from intraocular tumors in mice. AB - The role of the immune response in the elimination of spontaneous metastases arising from intraocular tumors was examined in a syngeneic intraocular murine tumor model. P91 mastocytoma (DBA/2 origin) expresses strong tumor-specific transplantation antigens and grows transiently in the eyes of syngeneic hosts before undergoing spontaneous rejection. An organ culture technique was used to detect spontaneous metastases in the lungs, spleens, brains, and thymuses of intraocular tumor-bearing mice. Metastatic tumor cells were detected in all organs of immunodeficient mice (i.e., athymic, nude, or x-irradiated DBA/2 mice) within 14 days of intraocular transplantation, and grew progressively thereafter. By contrast, metastatic tumors were rejected in 100% of the immunocompetent DBA/2 mice examined on day 15. Timed enucleation experiments demonstrated that the immune rejection of disseminated tumor cells occurred within 24-48 hr of their arrival at the various organs. The immune rejection of spontaneous metastases could be adoptively transferred to immunodeficient tumor-bearing mice using spleen cells, but not immune serum, from intraocular tumor-bearing immunocompetent donors. Selective cell depletion experiments revealed that the immune spleen cell effecting immunity was an Lyt 1+, 2+ T cell. The results indicate that the immune rejection of the spontaneous metastases arising from primary intraocular tumors is a T cell-dependent, radiosensitive process that rapidly eliminates metastases within the lungs, brain, thymus, and the spleen of the immunocompetent host. PMID- 3091528 TI - Nutrition and hydration as elective therapy: Brophy and Jobes from an ethical and historical perspective. PMID- 3091530 TI - Contribution of modern lithotripsy to the practice of urology. AB - Modern lithotripsy, both the minimally invasive percutaneous method and the completely noninvasive extracorporeal shock wave lithotripsy (ESWL) technique, have far-reaching effects on the practice of urology. The patient is spared a painful operation and convalescence, as well as surgical trauma to the kidney. The urologist needs to familiarize himself with the new techniques and, with the percutaneous method, must guard against radiation. The hospital is involved in considerable expense in purchasing and installing the ESWL equipment, and should redistribute its facilities to take full advantage of the rapid turnover it permits. The nation gains considerably by minimizing workdays lost due to surgical operations and convalescence, and by reducing the number of patients with kidney stones who ultimately require dialysis. PMID- 3091529 TI - Scientific and political issues in evaluating new technology: the case of shock wave lithotripsy. AB - In recent years many methods of surgical care have become available for the treatment of renal stones, but it seems that no single method is the answer to all situations. Although there is insufficient evidence to determine exactly which method is preferable for which type of stone, it is generally conceded that extracorporeal shock wave lithotripsy (ESWL) is a safe and effective technology for the treatment of urolithiasis in the proximal urinary tract. Even though the use of percutaneous lithotripsy has already become widespread, ESWL is being increasingly used in the U.S. today. PMID- 3091531 TI - Assessment of alternative technologies for the treatment of end-stage renal disease. AB - A general approach to the assessment of emerging medical technologies is illustrated by means of an analysis of the medical and fiscal impacts of the adoption of cyclosporin for immunosuppression in renal transplantation. The medical impacts evaluated include the effect on graft failure and patient mortality rates, on the incidence of rejection and other posttransplant complications, and on the level of functional rehabilitation achieved. The fiscal impacts examined include the effects on the cost of managing transplant recipients as well as of dialysis, because almost all renal transplanted patients were initially maintained on dialysis, and most graft failures result in return to chronic dialysis. Cyclosporin--despite being a very expensive drug--reduces the rate of cadaver-donor graft failure without increasing the overall costs of managing the recipients in the first 6 months post transplant. If cyclosporin can be discontinued within 3 years of transplantation, the medical benefits can be realized without added expenditures, principally because of the savings accrued due to a reduced need for maintenance dialysis. PMID- 3091532 TI - Cost-benefit of mass prophylaxis with immune serum globulin to control waterborne hepatitis A: a case study. AB - Following a point-source epidemic of more than 8,000 cases of Shigella sonnei, which was caused by a sewage-contaminated water supply, immune serum globulin (ISG) was administered to 11,306 children, aged 5 to 9 years, and to 1,338 pregnant women to prevent a possible outbreak of hepatitis A. A cost-benefit analysis showed that the estimated cost of preventing one possible case of hepatitis in a child was $362.50, and in a pregnant women $11,514. The benefit:cost ratios were 0.45 and 0.28, respectively. These relatively low ratios call for reconsideration of the guidelines that recommend ISG administration to children and pregnant women following an exposure to contaminated water. PMID- 3091533 TI - [New developments in the treatment of oligozoospermia]. AB - New developments in the treatment of oligozoospermia are discussed and critically considered. In particular, the necessity of performing double blind studies to test the efficacy of a drug is stressed. Generally, there is a great need for clinically orientated basic research in andrology since new approaches to scientifically orientated therapy are only possible if our current knowledge on physiology and pathophysiology of male reproductive functions is improved. In addition, a rational therapy can only be performed if sufficient selection criteria are available. The variety of new therapeutic means indicate that in the near future different approaches will be investigated to improve the success of andrological treatment, thus rendering therapy more effective for patients and doctors. PMID- 3091534 TI - [Chloroacetophenone allergy]. AB - Chloroacetophenone (CN) is used as a tear gas for riot control and as a kind of chemical Mace against small groups or individuals. Among other side-effects, CN can evoke toxic and allergic contact dermatitis, and more rarely exanthematous or anaphylactic reactions. It is difficult to distinguish between toxic and allergic reactions both in the clinical picture of dermatitis as well as on the basis of skin test reactions. We report on a patient with allergic contact dermatitis, which first appeared 5 days after exposure to CN as a sign of primary sensitization, leading to an intense eczematous reaction in skin tests. Allergy to CN does not appear to represent a handicap in normal daily life because it is solely used as tear gas and is of little significance as regards "cross allergies" to substances in the environment. PMID- 3091535 TI - A phase II clinical trial of the combination mitomycin C, adriamycin, and cis diamminedichloroplatinum in patients with advanced upper aerodigestive cancer. AB - Twenty-seven patients with assessable, regionally advanced, or metastatic upper aerodigestive cancer of diverse histology received a combination of mitomycin C, adriamycin, and cis-diamminedichloroplatinum. All patients had previously received extensive surgery and/or radiation therapy. We observed an overall 46% partial response rate (12/26). This included seven of 15 (47%) responders with squamous cell carcinoma. Six of those seven patients responded within the initial month of treatment. For all study participants, the median time to progression and survival was 3.8 months and 7.3 months, respectively. Moderate-to-severe nausea, vomiting, anorexia, and alopecia were the most common toxicities. Myelosuppression (WBC less than 4,100 cells/mm3) and thrombocytopenia (PLTS less than 130,000 cells/mm3) occurred in 100% and 71% of the 21 patients with nadir data recorded, respectively. There were no episodes of sepsis nor did we detect any meaningful impairment in renal function. This regimen is active in the previously treated head and neck cancer patient and can be conveniently administered on an outpatient basis with acceptable and manageable side effects. PMID- 3091536 TI - Patterns of failure in carcinoma of the nasopharynx: failure at distant sites. AB - Between 1970 and 1980, we treated 107 previously untreated patients with biopsy proven carcinoma of the nasopharynx by megavoltage external radiation therapy to the primary site, the base of the skull, and both sides of the neck. Eighty-seven percent of the patients had stage IV disease (American Joint Committee, 1980). Eighteen patients developed distant metastases as the first site of relapse. Metastases appeared within 6 months after treatment in 50% of these 18 patients, and in 94% within 2 years. Median survival after the development of distant metastases was 6 months. The most sensitive predictor of which patients would develop distant metastases was the size of cervical lymph node metastases at initial presentation (P = 0.003); patients without palpable cervical nodes or with cervical nodes smaller than 3 cm were the least likely to develop distant metastases (10%), followed by those patients who had cervical nodes measuring 3 to 6 cm (25%), followed by those who had cervical nodes larger than 6 cm, (almost 50%). The incidence of distant metastases was not significantly influenced by age, sex, birthplace, histology, or T-stage. Studies aimed at decreasing the morbidity and mortality from distant metastases in carcinoma of the nasopharynx should be undertaken in patients who present with bulky cervical metastases. PMID- 3091537 TI - Thoracotomy and gastrectomy in a patient with severe haemophilia A. PMID- 3091538 TI - Effects of Lactobacillus casei-containing ointment on the healing and protection against opportunistic infection of thermal injury wounds in mice. PMID- 3091539 TI - Periodate oxidation of glycolipids: a borohydride-periodate-Schiff method for ganglioside demonstration in tissue sections. AB - Among lipids, gangliosides can be selectively stained with Schiff's reagent if the oxidizing agent (sodium metaperiodate) is sufficiently dilute to exclude all but the readily oxidized sialic acid sugars. A borohydride-periodate-Schiff (BhPS) sequence is recommended as a reliable method, convenient to perform, for the detection of the intraneuronal lipid accumulations in the ganglioside storage disorders. PMID- 3091540 TI - The prevention of porphyrin loss from tissues during routine histological processing: quantitative studies on the Harderian gland. AB - The rodent Harderian gland is an important site of porphyrin biosynthesis and storage. Porphyrins are visible at the light and electron microscope level as large intraluminal accretions, as large interstitial accretions surrounded by foreign body giant cells, or as small interstitial deposits within free macrophages. Since porphyrins are soluble in a wide range of solvents, it is important to employ histological routines which minimize porphyrin loss during processing in addition to giving good tissue preservation. In this quantitative investigation, these requirements were optimally achieved with fixation in 3% buffered glutaraldehyde and the use of amyl acetate as a clearing agent. PMID- 3091541 TI - Thyroid stimulating and gonadotrophic hormones in pituitary adenomas without clinical or serological abnormality. AB - Forty-three chromophobe adenomas have been examined immunocytochemically for their hormonal content. Twelve cases with full pre-operative normal serum hormonal levels were found to have many positive cells within the tumour for thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH) and luteinizing hormone (LH). The specificity of the immunoreactive product within the tissue was checked by immunoabsorption. It is suggested that a non-secreted biologically inactive glycoprotein hormone is produced by tumour clones. PMID- 3091542 TI - Feeding the very-low-birthweight infant. PMID- 3091543 TI - Protein-energy malnutrition: the role of nutrition education in rehabilitation. AB - A randomized trial was carried out to test the effectiveness of nutrition education as a rehabilitation measure for childhood protein-energy malnutrition. The intervention comprised a series of home-based nutrition counselling sessions for the mothers/caretakers of 65 children (hospital outpatients) aged 7-36 months, who were suffering from mild to moderate protein-energy malnutrition. Both the intervention and control groups of children and their caretakers were assessed over a 12-month period: the children on admission and at 3-monthly intervals for weight-for-age, weight-for-height, height-for-age, triceps skinfold for-age and clinical features; the caretakers on admission and at the final follow-up for nutrition knowledge. Although the nutrition knowledge score of the caretakers in the intervention group improved significantly, no significant differences developed between the two groups of children regarding any of the nutritional status measures assessed. Thus, nutrition education per se was not found to be a major factor in promoting recovery from malnutrition. Nevertheless, both groups of children showed highly significant improvements in all age adjusted anthropometric assessments except height-for-age. PMID- 3091544 TI - Immunocytochemical localization of cathepsin H in rat kidney. Light and electron microscopic study. AB - Light and electron microscopic localization of cathepsin H in rat kidney was studied using post-embedding immunocytochemical techniques. For light microscopy, Epon sections of the kidney were stained by immunoenzyme method after removal of Epon and for electron microscopy, ultrathin sections of the Lowicryl K4M-embedded material were labeled by protein A-gold (pAg) technique. By light microscopy, fine granular staining was found in throughout the nephron, but the staining intensity considerably varied. The strongest staining was noted in the S1 segment of the proximal tubules followed by the S2 and S3 segments and the medullary collecting tubules. The glomeruli, the distal tubules, and the cortical collecting tubules were weakly stained. By electron microscopy, a gold label was found exclusively in lysosomes, which showed various sizes and labeling intensity. The results were quite consistent with the light microscopic results. The labeling intensity tended to increase as the matrix of lysosomes was condensed. Quantitative analysis of the labeling density of lysosomes demonstrated that the highest labeling density is found in the S1 segment of the proximal tubules and the labeling density of other renal segments is significantly low levels. The results indicate that a main site for cathepsin H in rat kidney is the S1 segment of the proximal tubules. PMID- 3091545 TI - Recognition of an HLA-DPw1 specific alloantiserum raised by planned immunization. AB - This study reports identification of the first alloantiserum specific for a single HLA-DP allele and presents valuable technical information for the serological detection of the HLA-DP gene product. Serological detection of the HLA-DP gene products was undertaken by analyzing a large number of alloantisera against an HLA-DP characterized, monocyte depleted, B-lymphocyte reference panel. After absorption of contaminating DR antibodies, one alloantiserum (SOW) which had been raised by planned immunization, was shown to have a correlation coefficient of 0.91 with DPw1 as defined by primed lymphocytes. No association was seen with any other HLA-A,-B,-C,-D,-DR, or -DQ specificity in either population or family studies. The HLA-DP typing of the serum donor and immunizing recipient support the conclusion. Evidence is presented which suggests that expression of the DP molecule is not stable, at least as detected by conventional microcytotoxicity techniques. PMID- 3091547 TI - [Guidelines for working with blood in Stockholm County]. PMID- 3091546 TI - Enhancement of EMT6/SF tumor cell killing by mitomycin C and cyclophosphamide following in vivo administration of buthionine sulfoximine. AB - We have examined the effect of L-buthionine sulfoximine (BSO) treatment on the subsequent cytotoxicity of mitomycin C (Mit C) and cyclophosphamide (CYC) in EMT6/SF tumors growing in Balb/c mice. GSH content in tumors decreased to a minimum level (less than 30% of control) 12 hr after a single injection of 5 mmole/kg of BSO. The recovery of tumor GSH was protracted and did not reach control levels up to 24 hr following BSO administration. Mit C and CYC were administered 12 hr after BSO injection. Tumor cell survival reached almost the same minimum level (SF = 0.050-0.06%) 1 hour after Mit C (10 mg/kg) treatment with or without BSO. However, 24 hr after Mit C treatment, survival had increased 36-fold (SF = 1.9%) in non-BSO-treated tumors compared to only 4-fold (SF = 0.3%) in the BSO-treated tumors. A dose modifying factor (DMF) of 1.4-1.8 was observed for BSO-pretreated tumors assayed 24 hr after Mit C administration. In CYC treated tumors, minimum surviving fractions were found 4 hr after CYC treatment with or without BSO treatment. These minimum survival levels were almost the same in BSO-treated tumors following 100 mg/kg CYC (SF = 0.03%) as in control tumors treated with 150 mg/kg CYC (SF = 0.04%). The same increase in cell survival was observed when tumor excision and assay were delayed 24 hr following CYC administration with or without prior BSO treatment. BSO treatment enhanced the cytotoxicity of CYC by DMFs of 1.6-1.9 based on the 24 hr excision assay. Depletion of tumor GSH by BSO caused enhancement of tumor cell killing by the two chemotherapy agents studied, either by increasing cytotoxicity, in the case of CYC or by decreasing PLD recovery following Mit C. PMID- 3091548 TI - [Switch from sterile to clean routine in delivery]. PMID- 3091549 TI - Enteral hyperalimentation administered via needle catheter-jejunostoma as an adjunct to cranial abdominal surgery in dogs and cats. AB - Ten dogs and 2 cats that underwent extensive cranial abdominal surgery were nutritionally maintained after surgery by enteral hyperalimentation administered via needle catheter-jejunostoma for an average of 8 days after surgery. Nine of the 12 patients survived the immediate postoperative period. PMID- 3091550 TI - Radioimmunoassay of c-myc protein. AB - A sensitive radioimmunoassay for human c-myc protein was developed by using an amino-terminal fragment of c-myc protein, c-myc(11-24). Immunoreactive c-myc protein was found to be present in 3 human tumors (HL-60, N231, Lu-65), which are known to have c-myc gene amplification. In contrast, c-myc protein was undetectable in 1 human tumor (H69) without c-myc gene amplification as well as in human heart tissues. PMID- 3091551 TI - Importance of follow-up of family history for understanding the genetic background of cancer. AB - The details of family histories naturally change as time passes. Thus, the family histories at the time of first consultation are incomplete, particularly in the cases of younger cancer patients whose disease is indicated as having a genetic background on the basis of epidemiological studies. The necessity for follow-up of the family history is illustrated by presenting some clinical cases as examples. PMID- 3091552 TI - Estimation of the number of cancer survivors in Japan. AB - Cancer prevalence statistics are necessary for cancer control programs. Although a long-term cancer registry keeps files which cover incidence, prevalence and cured cases, the latter two categories are difficult to distinguish from each other. The Connecticut and the Finnish Cancer Registries therefore defined the sum of these two groups as "prevalence." The authors estimated the numbers and rates of survivors from cancer ("prevalence") in Japan as of January 1, 1985, based on the number of cancer patients for all sites diagnosed since 1960. The number of cancer patients in Japan diagnosed during the period from 1960 to 1984 was estimated to be 4,686,352 (both sexes). Of these, the number of cancer survivors as of January 1, 1985 was estimated to be 952,870 (both sexes). Among the survivors, 430,940 were diagnosed in the final five years from 1980-84. The results were compared with those reported from the USA and Finland. PMID- 3091554 TI - Biosynthesis of pyrimidine nucleotides in human leukemic cells. AB - The biosynthetic pathways of pyrimidine nucleotides were studied in cells obtained from 10 patients with acute leukemia (AL), 3 with chronic myelocytic leukemia in blastic crisis (CML-crisis) and 4 with chronic myelocytic leukemia (CML) and from 8 controls. In the de novo pathway, synthesis of intermediates was analyzed with NaH[14C]O3 as a tracer. In the salvage pathway, the formation of nucleotides and free bases was studied with [3H]nucleosides (uridine, cytidine, thymidine, deoxyuridine, and deoxycytidine) tracers. Radioactivities of nucleotides were significantly lower in AL and CML-crisis cells than in CML and control cells in both pathways. These results suggest that the proliferative rate of cells was lower in the former cases than in the latter. Biosynthetic activities of nucleotides in the salvage pathway were about 100-300 times higher than those in the de novo pathway. It was calculated however, that as much as 70% of the amount of nucleic acids necessary for AL cells can be supplied by de novo biosynthesis, while in normal bone marrow cells the figure was about 30%. The greater part of pyrimidine biosynthesis can be carried out through the de novo pathway. In particular, AL cells with a longer generation time seemed to depend more on de novo biosynthesis than do normal bone marrow cells. This finding could be important in connection with the design of antileukemic agents. PMID- 3091553 TI - Effects of fatty acid modification of ascites tumor cells on pulmonary metastasis in rat. AB - Yoshida sarcoma cells were incubated with each of 4 different saturated and 17 different unsaturated fatty acid methyl and ethyl esters in order to modify the fatty acid composition of the cell membrane, and a possible correlation between the lipid fluidity of the cell membrane and the metastatic efficiency was studied. Almost all the unsaturated fatty acids used were incorporated into the tumor cell membrane, resulting in an increase of fluidity. In contrast, the incorporation of saturated fatty acids brought no change in fluidity. Exogenous treatment of the cells with palmitoleic acid (16:1, cis) induced a remarkable increase of membrane lipid fluidity resulting in easier passage of modified cells through capillary vessels, which was detected in an in vitro perfusion test of the lung. Intravenous injection of the modified cells resulted in fewer metastatic foci in the lung as compared with that of unmodified cells. A similar effect on lung metastasis was also observed in exogenous modification of the cells by linoleic acid (18:2, cis) or linolenic acid (18:3, n-3). On the other hand, although exogenous eicosapentaenoic acid (20:5, n-3) and docosahexaenoic acid (22:6, n-3) treatments induced a slight increase in the lipid fluidity of the cells, intravenous injection of the cells produced a significant increase in their metastatic potential in the lung. Interestingly, the treatment with 20:5 and 22:6 produced increased stickiness of the cells to a glass surface and reduced cellular passage through the vessels as detected by the lung perfusion test. Thus, the present results suggested that selective modification of membrane fatty acid may be a useful method for artificial regulation of the ability of circulating tumor cells to pass through vessels. PMID- 3091555 TI - Characteristics of resistance to adriamycin in human myelogenous leukemia K562 resistant to adriamycin and in isolated clones. AB - An adriamycin (ADM)-resistant variant (K562/ADM) of human myelogenous leukemia K562 was established. K562/ADM was stable for 2 months in medium without ADM, and was 130-fold more resistant to ADM as compared to the parent K562. Twenty clones were isolated from K562/ADM by the limiting dilution technique. Five clones with different ADM sensitivity were selected and characterized further. The extent of clonal resistance to ADM was parallel to the extent of resistance to vincristine (VCR), except for one clone, KA-15. The majority of clones, including K562/ADM, accumulated far smaller amounts of daunomycin (DAU) or VCR as compared to the parent K562. However, a highly resistant clone did not necessarily accumulate less DAU in the cells, indicating that the mechanism of ADM resistance cannot be explained solely by a defect of ADM accumulation. All clones rapidly transported DAU and VCR from the cells. K562/ADM expressed on the cell surface three distinct glycoproteins with molecular weights of 180,000, 83,000 and 65,000 daltons. No change was detected in the actin and tubulin contents of K562 and clones. K562/ADM and its clones expressed double minute chromosomes and contained homogeneously staining regions in the chromosomes. PMID- 3091556 TI - A T cell leukemia line produces factor(s) that render rat neutrophils cytotoxic. AB - Proteose-peptone-induced intraperitoneal neutrophils from rats were activated in terms of tumor cytotoxicity by pretreatment with culture supernatants from a human T cell leukemia line, Jurkat (culture sup). Culture sup-treated neutrophils showed cytotoxicity against various tumor cell lines. The cytotoxicity of culture sup-treated neutrophils was dependent on the number of neutrophils and the concentration of culture sup. Cytostasis by activated neutrophils was observed very early in the assay incubation period (within 6 hr), but cytolysis first occurred at 24 hr after the start of incubation. Factor(s) in culture sup responsible for the activation of cytotoxic neutrophils were stable to temperature and pH treatments, and their molecular weight was higher than 10,000. The responsible factor(s) for activation of cytotoxic neutrophils were different from interleukin-2, serum-derived factor, and bacterial lipopolysaccharide. PMID- 3091557 TI - Induction by Lactobacillus casei of increase in macrophage colony-forming cells and serum colony-stimulating activity in mice. AB - The content of macrophage colony-forming cells (M-CFC) and the serum colony stimulating activity (CSA) were investigated in mice after intravenous administration of Lactobacillus casei YIT9018 (LC9018). In normal BALB/c mice, 500 micrograms of LC9018 increased both femoral and splenic M-CFC; the highest levels were found a few days and a week, respectively, after the administration. LC9018 also induced an increase in splenic M-CFC in C3H/HeJ mice as well as in C3H/HeN mice, unlike lipopolysaccharide (LPS), which was ineffective in C3H/HeJ mice. In Meth A-bearing BALB/c mice, LC9018 (250 micrograms X 5) suppressed the growth of tumor cells and increased femoral and splenic M-CFC to much greater extents than Lactobacillus plantarum YIT0102 (250 micrograms X 5) did. LC9018 induced a rise of serum granulocyte-macrophage CSA in the same way as LPS. Sera taken 6 hr after LPS administration, when transferred to normal mice, induced increases in femoral and splenic M-CFC. However, sera taken 6 hr after LC9018 administration increased neither femoral nor splenic M-CFC. These results indicate that LC9018 modulates myelopoiesis at least at the stage of the proliferation of M-CFC in a different way from LPS, and this ability may be related to its antitumor activity. PMID- 3091558 TI - The role of I-region associated antigen (Ia)-bearing accessory cells in the generation of cytotoxic T cells in a subpopulation of thymocytes. AB - The roles of killer-helper factor (KHF) and accessory cells bearing I-region associated antigen (Ia) in the generation of cytotoxic T lymphocytes (CTL) were analyzed. Peanut agglutinin-binding (PNA+) thymocytes from C3H/HeN mice generated efficient CTL responses against 2,4,6-trinitrophenyl (TNP)-modified syngeneic spleen cells in the presence of cell-free supernatant (CFS) derived from purified protein derivatives (PPD)-stimulated Mycobacterium tuberculosis-primed BALB/c spleen cell culture (PPD-CFS). The KHF which is present in PPD-CFS devoid of the activities of IL-1 or IL-2 was required in conjunction with IL-2 for generation of CTL in PNA+ thymocytes. In contrast, PNA- thymocytes as well as spleen cells could generate CTL in the absence of helper factors. However, a significant CTL response against Ia-negative syngeneic tumor cells was not induced from either PNA+, PNA- thymocytes or spleen cells in the absence of Ia-positive accessory cells. Moreover, the treatment of spleen cells with relevant anti-Ia antiserum plus complement before TNP-modification abrogated the stimulatory capacity of TNP spleen cells. In both cases, the addition of Ia-positive accessory cells restored the impaired capacity of TNP-modified stimulator cells. The addition of IL-1 to the culture of PNA- thymocytes or spleen cells stimulated with TNP-X5563 cells in the absence of accessory cells restored the CTL generation. In contrast, the addition of IL-1 to the culture of PNA+ thymocytes was ineffective. The role of Ia-positive accessory cells in the generation of CTL in a subpopulation of thymocytes is discussed. PMID- 3091559 TI - Preparation of human monoclonal antibodies of IgG type to gastro-intestinal cancer-associated antigen. AB - The B lymphocytes from pleural effusion of a gastric cancer patient were fused with murine myeloma cells (X63-Ag8.653). Thirty-four out of 62 clones were found to secrete human monoclonal antibodies (23 IgGs and 11 IgMs) by means of enzyme linked immunosorbent assay. Fourteen monoclonal antibodies were tested for histological reactivity with cancer and normal tissues by immunoperoxidase staining. Among them, two monoclonal antibodies reacted rather specifically with gastro-intestinal cancerous tissues. The human monoclonal antibody (HMoAb) 3B7 (IgG) reacted strongly with 4 out of 5 gastric carcinoma tissues and 2 out of 5 colonic carcinoma tissues, but did not react with non-cancerous tissues (stomach, colon, liver, pancreas and lung). In addition, HMoAb 3B7 reacted heterogeneously with autologous gastric carcinoma tissue sections. The hybridoma 3B7 has continued producing human monoclonal antibody for 12 months after fusion. By chromosomal analysis, it was shown that hybridoma 3B7 retains both human and mouse chromosomes. HMoAb 3B7 may be useful for research on tumor-associated antigens and therapeutic techniques. PMID- 3091560 TI - Regulation of gonadotropin secretion in the male: effect of an aromatization inhibitor in estradiol-implanted, orchidectomized dogs. AB - Testosterone is aromatized to estradiol in both peripheral tissues and the central nervous system. Various authors have suggested that this conversion in the male may be prerequisite for the regulation of gonadotropin secretion by testosterone. Previously, it was reported that inhibition of central nervous system aromatase caused a significant increase in plasma LH in the presence of physiologic testosterone levels (Winter et al, 1983). In order to confirm whether aminoglutethimide, the aromatase inhibitor used in our previous study, either blocked aromatization, or the action of estradiol, the following study was conducted. Fifteen male mongrel dogs were equally divided into three groups. Group 1 dogs were implanted with estradiol-filled polydimethylsiloxane capsules only; Group 2 dogs were implanted with empty capsules and treated with 60 mg b.i.d. of aminoglutethimide; and Group 3 dogs were implanted with polydimethylsiloxane capsules filled with estradiol and treated with aminoglutethimide. Blood samples were drawn for 24 days during pretreatment, capsule implantation, castration, aminoglutethimide administration and capsule removal periods. The postcastration response of both plasma LH and FSH in dogs in groups 1 and 3 was suppressed in the presence of elevated estradiol, whereas that of Group 2 dogs was normal in the absence of estradiol. The results suggest that aminoglutethimide neither directly affects the plasma concentration of either LH or FSH nor blocks the effect of estradiol in inhibiting their release following castration. These data, taken together with our previous work, implicate aromatization of testosterone to estradiol in the control of gonadotropin secretion in the male. PMID- 3091561 TI - Survival and growth of Bacillus cereus in bread. AB - Bread doughs were artificially inoculated with spores of six Bacillus cereus strains at different inoculum levels and counts of survivors in bread determined during storage at 27.5 degrees C. No B. cereus were isolated from the centre crumb of 400 g loaves when the dough contained less than 10(4) spores/g whereas with 800 g loaves survival occurred with doughs containing 5.0 X 10(3) spores/g. With all strains there was a period of at least 24 h before multiplication took place in the bread. The inclusion in dough of 0.2% of calcium propionate, based on flour, effectively delayed germination and subsequent multiplication of B. cereus spores. It is concluded that the risk of food poisoning due to the presence of B. cereus in bread is minimal. PMID- 3091562 TI - The carrier state: methicillin-resistant Staphylococcus aureus. PMID- 3091563 TI - The carrier state: Neisseria meningitidis. PMID- 3091564 TI - The carrier state: Neisseria gonorrhoeae. PMID- 3091565 TI - Effects of regional alveolar hypoxia and hypercapnia on small pulmonary vessels in cats. AB - Using an X-ray TV system, we analyzed responses in the internal diameter (ID), flow velocity, and volume flow in small pulmonary vessels (100-600 microns ID) during unilobar hypoxia and hypercapnia in cats. In the hypoxic and hypercapnic lobes, the ID reduced in proportion to the degree of hypoxia and hypercapnia, respectively. The ID reduction was larger in the arteries than in the veins for a given stimulus. In the arteries, the ID reduced nonuniformly in the series arranged vessels in response to both stimuli. The percentage ID reduction was maximal in the arteries of 200-300 microns ID, in which it was 21, 26, 28, and 36% with 5% O2, 0% O2, 5% CO2, and 10% CO2 inhalations, respectively. On the other hand, in the veins, uniform ID reduction occurred for a given stimulus. In the contralateral normoxic lobe, the ID did not change significantly. In both hypoxic and hypercapnic lobes, the flow velocity and volume flow of the small arteries decreased, with 5% O2, by 18 and 40%, respectively, and, with 5% CO2, by 23 and 50%, respectively. In contrast, in the normoxic lobe, they increased significantly during 5% O2 and 5% CO2 inhalations. We concluded that regional alveolar hypoxia and hypercapnia induced a local vasoconstriction particularly in the small arteries of 200-300 microns ID and decreased the flow velocity and volume flow in the same lung region. PMID- 3091566 TI - Effect of centrally administered gamma-aminobutyric acid on metabolic function. AB - gamma-Aminobutyric acid (GABA) content of the brain increases during hypoxia and hypercapnia and GABA by itself is a central ventilatory depressant and may depress metabolism as well. Therefore the effect of centrally administered GABA by ventriculocisternal perfusion on O2 consumption (VO2) and CO2 production (VCO2) was studied in pentobarbital-anesthetized dogs. GABA (30 mM) in mock cerebrospinal fluid (CSF) was perfused for 15 min at the rate of 1.0 ml/min followed by perfusion with mock CSF alone. Body temperature, perfusion pressure, and CSF pH were kept constant. Minute ventilation (VE) was kept constant mechanically. Under these conditions, VO2, VCO2, alveolar ventilation (VA), and relative pulmonary dead space volume (VD/VT) were measured. During perfusion with 30 mM GABA, mean VO2 (+/- SE) decreased from 96.5 +/- 3.3 to 81.9 +/- 5.1 ml/min, VCO2 from 72.1 +/- 3.8 to 60.7 +/- 3.0 ml/min, and VA from 1.7 +/- 0.1 to 1.3 +/- 0.1 l/min. VD/VT increased from 0.55 +/- 0.02 to 0.65 +/- 0.01. Perfusion with mock CSF alone restored these parameters to initial levels within 15 min. We conclude that centrally administered GABA depresses VO2 and VCO2. This reduction in metabolic function is independent of the central modulatory effects of GABA on respiration. PMID- 3091567 TI - Control of ventilation in extreme-altitude climbers. AB - Ten climbers who participated in the Nepal-Japan Kangchenjunga Expedition (altitude, 8,478-8,586 m) in 1984 were examined for their hypercapnic and isocapnic hypoxic ventilatory responses (HCVR and HVR) at sea level before and after the expedition. Five climbers who reached an altitude higher than 8,000 m, [designated high-performance climbers (HPC)] exhibited significantly higher HVR than five climbers who did not [low-performance climbers (LPC)]. On the other hand, no significant difference in HCVR was seen between HPC and LPC. Our results were in agreement with the findings reported by Schoene et al. (J. Appl. Physiol. 56: 1478-1483, 1984) obtained in the American Medical Research Expedition to Everest in 1981. Significant depression in HVR in five climbers was found even 35 40 days after the expedition, which was accompanied by decreased arterial partial pressure of CO2 and increased pH at rest. Hence, the effect of altitude acclimatization in the climbers exposed to extreme altitude may have still persisted at the time of the postexpedition study. Our results confirmed that HRV evaluated at sea level may be used as an indicator of a climber's capability at great high altitude. PMID- 3091568 TI - Cardiopulmonary response to extracorporeal venous CO2 removal in awake spontaneously breathing dogs. AB - The ventilatory response to a reduction in mixed venous PCO2 has been reported to be a decrease in breathing even to the point of apnea with no change in arterial CO2 partial pressure (PaCO2), whereas a recent report in exercising dogs found a small but significant drop in PaCO2 (F. M. Bennett et al. J. Appl. Physiol. 56: 1335-1337, 1984). The purpose of the present study was to attempt to reconcile this discrepancy by carefully investigating the cardiopulmonary response to venous CO2 removal over the entire range from eupnea to the apneic threshold in awake, spontaneously breathing normoxic dogs. Six dogs with chronic tracheostomies were prepared with bilateral femoral arteriovenous shunts under general anesthesia. Following recovery, an extracorporeal venovenous bypass circuit, consisting of a roller pump and a silicone-membrane gas exchanger, was attached to the femoral venous cannulas. Cardiopulmonary responses were measured during removal of CO2 from the venous blood and during inhalation of low levels of CO2. Arterial PO2 was kept constant by adjusting inspired O2. The response to venous CO2 unloading was a reduction in PaCO2 and minute ventilation (VE). The slope of the response, delta VE/delta PaCO2, was the same as that observed during CO2 inhalation. This response continued linearly to the point of apnea without significant changes in cardiovascular function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091569 TI - Effect of hyperoxia on substrate utilization during intense submaximal exercise. AB - Six trained males [mean maximal O2 uptake (VO2max) = 66 ml X kg-1 X min-1] performed 30 min of cycling (mean = 76.8% VO2max) during normoxia (21.35 +/- 0.16% O2) and hyperoxia (61.34 +/- 1.0% O2). Values for VO2, CO2 output (VCO2), minute ventilation (VE), respiratory exchange ratio (RER), venous lactate, glycerol, free fatty acids, glucose, and alanine were obtained before, during, and after the exercise bout to investigate the possibility that a substrate shift is responsible for the previously observed enhanced performance and decreased RER during exercise with hyperoxia. VO2, free fatty acids, glucose, and alanine values were not significantly different in hyperoxia compared with normoxia. VCO2, RER, VE, and glycerol and lactate levels were all lower during hyperoxia. These results are interpreted to support the possibility of a substrate shift during hyperoxia. PMID- 3091571 TI - Liberation of muscle carbonic anhydrase into serum during extensive exercise. AB - A sensitive radioimmunoassay method for measurement of human carbonic anhydrase III (CA III), a specific enzyme of skeletal muscle, was established. The effect of 24-h competitive running on serum CA III (S-CA III) was studied in healthy male long-distance runners. S-CA III increased gradually during the first 18 h 410-fold above the initial values. No further increase was observed during the last 6 h. On a day after the termination of the race S-CA III was not statistically different from the initial value. The activity of serum creatine kinase (S-CK) and lactate dehydrogenase (S-LDH) increased gradually through the run being elevated also 1 or 2 days afterward. The lack of increase in S-CA III during the last hours of exercise, and more rapid decrease afterward than in S-CK or S-LDH, may reflect differences in the rates of penetration through the sarcolemma and different degrees of injury in different fiber types or in the half-lives of these enzymes in serum. PMID- 3091570 TI - Effect of hypoxia on permeability of pulmonary endothelium of canine visceral pleura. AB - To determine if hypoxia increases the permeability of the pulmonary capillaries of the visceral pleura, water and protein movement across visceral pleura of isolated blood-perfused lungs ventilated with 20% O2-5% CO2 or 0% O2-5% CO2 was analyzed in terms of a two-compartment model of fluid exchange. Lungs from mongrel dogs were enclosed in a water-impermeable membrane, thereby creating an artificial visceral pleural space (VPS); fluid flux was determined as the filtration or reabsorption of water and protein in the VPS. Hypoxic vasoconstriction was prevented by adding verapamil to the perfusate. Hydrostatic pressures were continuously monitored and samples of perfusate and pleural fluid were obtained for protein determinations. Pulmonary capillary pressure was varied between 5 and 20 Torr by changing venous pressure while the protein concentration gradient was varied from 0.5 to 6.6 g/dl by introducing different solutions of plasma mixed with saline into the VPS. The hydraulic conductivity (Lp) increased from 4.25 +/- 0.74 to 9.18 +/- 0.67 X 10(-7) ml X s-1 X mmHg-1 X cm-2 and the diffusional permeability (Pd) of protein increased from 1.29 +/- 0.28 to 4.06 +/- 0.44 X 10(-6) cm/s under hypoxic conditions (P less than 0.05). Inhibition of xanthine oxidase by the addition of allopurinol (10 mg/kg body wt) to the perfusate prevented the increase in Lp and Pd observed under hypoxic conditions. We conclude that free radicals generated via xanthine oxidase may be responsible for the increased permeability observed during severe hypoxia. PMID- 3091572 TI - Arterial hypocapnia during exercise in beagle dogs. AB - Previous investigators have assumed that during exercise there is a tight coupling of ventilation with CO2 delivery to the lungs such that arterial blood remains isocapnic. We measured arterial blood gases in a group of 10 beagle dogs in which arterial blood sampling could be accomplished via exteriorized carotid artery loops and in six of the same dogs following chronic pulmonary denervation. Samples were taken at rest, at 15-s intervals during the first minute of unrestrained treadmill exercise at 5.0 km/h, 0% grade, and then at 2 and 3 min at the same work load. Mean resting arterial PCO2 for the control dogs was 37.1 Torr. At the onset of exercise arterial PCO2 fell progressively to a nadir of 34.6 Torr during the 30- to 45-s sampling period. Samples at 2 and 3 min remained significantly hypocapnic (PCO2 = 34.8 Torr). The arterial PCO2 and pH responses to exercise in the lung-denervated dogs were not significantly different from those of the control dogs, although arterial PO2 was lower at rest and during exercise following denervation of the lungs. The arterial hypocapnia exhibited in intact beagle dogs at the onset of exercise persists into the steady state and suggests that there is not a tight coupling of ventilation with pulmonary CO2 delivery. The similarity of the response in lung-denervated dogs suggests that intrapulmonary receptors with afferents in the vagi are not the primary mediators of the ventilatory response to exercise. PMID- 3091573 TI - Electrical and mechanical activity of respiratory muscles during hypercapnia. AB - In nine anesthetized supine spontaneously breathing dogs, we compared moving average electromyograms (EMGs) of the costal diaphragm and the third parasternal intercostal muscles with their respective respiratory changes in length (measured by sonomicrometry). During resting O2 breathing the pattern of diaphragm and intercostal muscle inspiratory shortening paralleled the gradually incrementing pattern of their moving average EMGs. Progressive hypercapnia caused progressive increases in the amount and velocity of respiratory muscle inspiratory shortening. For both muscles there were linear relationships during the course of CO2 rebreathing between their peak moving average EMGs and total inspiratory shortening and between tidal volume and total inspiratory shortening. During single-breath airway occlusions, the electrical activity of both the diaphragm and intercostal muscles increased, but there were decreases in their tidal shortening. The extent of muscle shortening during occluded breaths was increased by hypercapnia, so that both muscles shortened more during occluded breaths under hypercapnic conditions (PCO2 up to 90 Torr) than during unoccluded breaths under normocapnic conditions. These results suggest that for the costal diaphragm and parasternal intercostal muscles there is a close relationship between their electrical and mechanical behavior during CO2 rebreathing, this relationship is substantially altered by occluding the airway for a single breath, and thoracic respiratory muscles do not contract quasi-isometrically during occluded breaths. PMID- 3091574 TI - Effect of reducing anatomic dead space on arterial PCO2 during CO2 inhalation. AB - Carotid body-denervated (CBD) ponies have a less than normal increase in arterial PCO2 (PaCO2) when inspired CO2 (PICO2) is increased, even when pulmonary ventilation (VE) and breathing frequency (f) are normal. We studied six tracheostomized ponies to determine whether this change 1) might be due to increased alveolar ventilation (VA) secondary to a reduction in upper airway dead space (VD) or 2) is dependent on an upper airway sensory mechanism. Three normal and three chronic CBD ponies were studied while they were breathing room air and at 14, 28, and 42 Torr PICO2. While the ponies were breathing room air, physiological VD was 483 and 255 ml during nares breathing (NBr) and tracheostomy breathing (TBr), respectively. However, at elevated PICO2, mixed expired PCO2 often exceeded PaCO2; thus we were unable to calculate physiological VD using the Bohr equation. At all PICO2 in normal ponies, PaCO2 was approximately 0.3 Torr greater during NBr than during TBr (P less than 0.05). In CBD ponies this NBr-TBr difference was only evident while breathing room air and at 28 Torr PICO2. At each elevated PICO2 during both NBr and TBr, the increase in PaCO2 above control was always less in CBD ponies than in normal ponies (P less than 0.01). The VE PaCO2, f-PaCO2, and tidal volume-PaCO2 relationships did not differ between NBr and TBr (P greater than 0.10) nor did they differ between normal and CBD ponies (P greater than 0.10). We conclude that the attenuated increase in PaCO2 during CO2 inhalation after CBD is not due to a relative increase in VA secondary to reducing upper airway VD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091575 TI - Bronchial responsiveness to nonantigenic bronchoconstrictors in awake sheep. AB - The experiments were designed to further characterize pulmonary responsiveness to nonantigenic aerosol bronchoconstrictors in unanesthetized sheep. The distribution of aerosol histamine responsiveness was described among 55 sheep. Within day reproducibility of aerosol histamine (n = 18) and carbachol (n = 8) responsiveness was studied and aerosol histamine and carbachol responsiveness were compared (n = 9). The effects of cyclooxygenase inhibition with meclofenamate (n = 7) and ibuprofen (n = 8) on pulmonary responsiveness to aerosol histamine was studied as was the effect of ibuprofen (n = 6) on pulmonary responsiveness to aerosol carbachol. A log normal unimodal distribution of pulmonary responsiveness to aerosol histamine was described. Within day pulmonary responsiveness to aerosol histamine was highly reproducible while pulmonary responsiveness to aerosol carbachol decreased slightly, but not significantly, on the second challenge. Pulmonary responsiveness to aerosol histamine correlated with pulmonary responsiveness to aerosol carbachol (r = 0.85, P less than 0.05). Meclofenamate did not significantly attenuate pulmonary responsiveness to aerosol histamine. Ibuprofen attenuated pulmonary responsiveness to aerosol histamine (P less than 0.05) but not to aerosol carbachol. These experiments supply basic information related to pulmonary responsiveness to nonantigenic bronchoconstrictors in awake sheep. PMID- 3091576 TI - Thin layer chromatography and densitometric determination of aflatoxins in mixed feeds containing citrus pulp. AB - A method for the accurate one-dimensional thin layer chromatographic (TLC) determination of aflatoxins B1, B2, G1, and G2 in mixed feeds is presented. The aflatoxins are extracted from the sample with chloroform and purified by solvent partitioning. Each aflatoxin is separated from pulp interference by thin layer chromatography on aluminum-backed silica plates. The separated aflatoxins are detected by fluorescence densitometry. Average recoveries for samples spiked from 10 to 100 ppb B1 and G1 and from 3 to 30 ppb B2 and G2 are 82, 84, 95, and 94% for B1, B2, G1, and G2, respectively. The above recovery data, when analyzed for overall method repeatability, produced relative standard deviations of 6.8, 4.3, 6.9, and 7.6% for B1, B2, G1, and G2, respectively. Minimum detection level is less than 1 ppb for each aflatoxin. B1 is confirmed by trifluoroacetic acid derivative formation on a silica TLC plate. PMID- 3091577 TI - A 26-base-pair repetitive sequence specific for Neisseria gonorrhoeae and Neisseria meningitidis genomic DNA. AB - Two-dimensional heteroduplex mapping of Neisseria gonorrhoeae genomic DNA revealed a number of spots, indicating the existence of repetitive sequences. When one of the spots was extracted and used as a probe for Southern blot analysis, two HindIII bands (11.0 and 3.6 kilobases [kb]) of the genomic digest hybridized with approximately equal intensity. The 3.6-kb fragment was cloned and found to contain two different types of repeated sequence. One type was approximately 1.1 kb in length and was found at least twice in the entire genome. The other consisted of a 26-base-pair family GT(C/A)C(Py)G(Pu)TTTTTGTTAAT(Py)C(Pu)CTATA (Py, pyrimidine; Pu, purine) that was repeated at least 20 times in the entire genome. This repetitive sequence was found also in Neisseria meningitidis but not in various other gram-negative bacteria. PMID- 3091578 TI - Heterospecific transformation among cyanobacteria. AB - Heterospecific transformation occurred between cyanobacteria currently classified in either the genus Synechococcus or Synechocystis. Cyanobacterial strains 73109 and 6906 were capable of physiological transformation. PMID- 3091579 TI - Regulatory elements common to the Bacillus pumilus and Bacillus subtilis trp operons. AB - The trp operon regulatory region of Bacillus pumilus was cloned and sequenced. The cloned B. pumilus trp promoter-leader region functioned in Bacillus subtilis to express the adjacent leukocyte interferon A gene on a multicopy transcriptional fusion plasmid, pBpIFI. In strains carrying this plasmid, anthranilate synthetase levels were elevated, possible due to titration of a B. subtilis trp regulatory factor by multiple copies of the transcript of the plasmid-borne B. pumilus trp leader region. The B. pumilus trp promoter was recognized efficiently in vitro by B. subtilis sigma 43 RNA polymerase. Approximately 12% of the transcripts produced in vitro terminated in the leader region immediately following synthesis of a transcript structure resembling rho independent terminators of enteric bacteria. An analogous terminator exists in the B. subtilis trp leader transcript. Nucleotide sequence comparison of the B. pumilus and B. subtilis trp leader regions revealed conservation of these and other sequences that could form transcript secondary structures postulated to regulate transcription termination in B. subtilis (H. Shimotsu, M.I. Kuroda, C. Yanofsky, and D.J. Henner, J. Bacteriol. 166:461-471, 1986). We propose that two elements implicated in B. subtilis trp operon regulation are conserved in the related organism B. pumilus: alternative transcription antiterminator and terminator structures in the leader transcript, and a trans-acting factor present in limiting amounts that is required for transcription termination in the leader region. PMID- 3091580 TI - Acquisition of glucose by Rickettsia prowazekii through the nucleotide intermediate uridine 5'-diphosphoglucose. AB - The ability of Rickettsia prowazekii to transport potential sources of the glucose moiety of bacterial polysaccharides was determined. Transport was determined both by filtration assays and by centrifugation through nonaqueous layers. Uridine 5'-diphosphoglucose (UDPG) was transported, whereas glucose was not transported; the uptake of glucose phosphates, although greater than that for glucose, was markedly lower than the transport of UDPG. Furthermore, the activities of hexokinase and phosphoglucomutase, enzymes required for the metabolism of glucose and glucose 6-phosphate, were undetectable in rickettsial extracts. The uptake of UDPG had an extended time course and did not reach a plateau until 60 min. The maximum rate of uptake was 340 pmol/min per mg of protein, and the rate was half-maximal at a UDPG concentration of 220 microM. Measurement of true influx of UDPG was complicated by the low activity of this transport system and the metabolism of the UDPG. The uptake of labeled UDPG was markedly inhibited by a 10-fold excess of uridine monophosphate, uridine diphospho-N-acetylglucosamine, and uridine diphospho-N-acetylgalactosamine but not by a variety of other structurally related compounds. PMID- 3091581 TI - Molecular and genetic characterization of lactose-metabolic genes of Streptococcus cremoris. AB - Lac+ plasmid DNA from Streptococcus cremoris H2 was subcloned with an Escherichia coli vector on a 3.5-kilobase-pair PstI-AvaI fragment. Genetic analysis of the cloned DNA was possible because linear Lac+ DNA fragments were productive in the S. sanguis transformation system. Complementation of S. sanguis Lac-mutants showed that the 3.5-kilobase-pair fragment included the structural gene for 6 phospho-beta-D-galactosidase and either enzyme II-lac or factor III-lac of the lactose-specific phosphoenolpyruvate-dependent phosphotransferase system. Expression of the S. cremoris-like 40,000-dalton 6-phospho-beta-D-galactosidase in S. sanguis Lac+ transformants, rather than the 52,000-dalton wild-type S. sanguis enzyme, demonstrated the occurrence of gene replacement and not gene repair. The evidence supports chromosomal integration as the mechanism by which S. sanguis Lac- recipients are converted to a Lac+ phenotype after transformation with Lac+ DNA. Southern blot data suggest that the Lac+ DNA does not reside on a transposon, but that integration always occurs within a specific HincII fragment of the recipient chromosome. Hybridization experiments demonstrate homology between the S. cremoris Lac+ DNA and cellular DNA from Lac+ strains of Streptococcus lactis, S. mutans, S. faecalis, and S. sanguis. PMID- 3091583 TI - Control of lysogeny and immunity of Bacillus subtilis temperate bacteriophage SP beta by its d gene. AB - The d gene from the Bacillus subtilis temperate bacteriophage SP beta was isolated. When introduced into an SP beta-sensitive strain of B. subtilis, the cloned d gene directed the synthesis of a 22-kilodalton protein and conferred on the host immunity to SP beta phage. A frameshift mutation, designated d2, was introduced into the cloned d gene, and it was subsequently crossed back into the SP beta phage genome. The resulting SP beta phage grew lytically and formed clear plaques on sensitive bacteria. Although the cloned d gene confers immunity to the host, we could not detect complementation of the d gene by mixed infection with SP beta d2 and various SP beta c mutants. The nucleotide sequence of the 1,033 base-pair PstI-to-EcoRI fragment containing the d gene was determined; it includes an open reading frame that could potentially encode a protein of 227 amino acids. The gene was mapped within the PstI H fragment on the phage genome, which positions the d gene about 25 kilobases from the right end of the phage genome. It is transcribed from right to left. PMID- 3091582 TI - Nucleotide sequence of the constitutive macrolide-lincosamide-streptogramin B resistance plasmid pNE131 from Staphylococcus epidermidis and homologies with Staphylococcus aureus plasmids pE194 and pSN2. AB - The complete nucleotide sequence of the Staphylococcus epidermidis plasmid pNE131 is presented. The plasmid is 2,355 base pairs long and contains two major open reading frames. A comparison of the pNE131 DNA sequence with the published DNA sequences of five Staphylococcus aureus plasmids revealed strong regional homologies with two of them, pE194 and pSN2. The region of pNE131 containing the reading frame which encodes the constitutive ermM gene is almost identical to the inducible ermC gene region of pE194, except for a 107-base-pair deletion which removes the mRNA leader sequence required for inducible expression. A second region of pNE131 contains an open reading frame with homology to the small cryptic plasmid pSN2 and potentially encodes a 162-amino-acid protein. PMID- 3091584 TI - Clonazepam blockade of spontaneous and CO2 inhalation-provoked panic in a patient with panic disorder. AB - A 30-year-old woman with panic disorder and phobic avoidance responded partially to treatment with alprazolam but recovered fully while receiving clonazepam, which blocked her panic attacks and anticipatory anxiety. Before treatment, the patient underwent a carbon dioxide inhalation test as a challenge and sustained a full-featured panic attack. After clonazepam therapy and retesting under identical conditions, no panic attack was reported. This is the first report of provoked panic blocked by clonazepam, a putative, clinically effective antipanic agent. PMID- 3091585 TI - Purification of natural human interferon-gamma by antibody affinity chromatography: analysis of constituent protein species in the dimers. AB - A simple procedure for purifying human interferon-gamma from leukocytes was established, based on monoclonal antibody affinity chromatography. The recovery of interferon activity was essentially quantitative, and the specific activity of the product was (4-12) x 10(7) international units/mg protein. SDS-polyacrylamide gel electrophoresis reproducibly revealed four components associated with interferon activity (and no other proteins): two major ones with molecular weights (MW) of 24,000-25,000 (25K) and 19,000-20,000 (20K), a minor one with MW 14,000-15,000 (15K) (these three bands were doublets), and a still less prominent one(s) with MV 40,000-48,000. Gel filtration in neutral solution indicated that all the 25K, 20K, and 15K species exist as oligomers, probably dimers. By means of experiments using a cleavable crosslinking reagent, the dimers were shown to comprise both homo-and heterodimers. Gel filtration in alkali (the condition used during purification) indicated that the molecules are largely in a monomeric state. Thus, the molecules once dissociated in alkali appear to reassociate at random upon neutralization; this process takes place without being accompanied by inactivation. PMID- 3091587 TI - Potentiation by retinoic acid of ornithine decarboxylase induction by phytohemagglutinin or phorbol 12-myristate 13-acetate in guinea pig lymphocytes. AB - Retinoic acid potentiated the increases in ornithine decarboxylase (L-ornithine carboxy-lyase [EC 4.1.1.17]) activity, [3H]difluoromethylornithine binding to ornithine decarboxylase, intracellular levels of polyamines and DNA synthesis in guinea pig lymphocytes stimulated with phytohemagglutinin. The stimulatory effect on the ornithine decarboxylase induction was dependent on the dose of retinoic acid and on the time of addition of the drug. Retinoic acid has to be added not later than 2 h after phytohemagglutinin to elicit the potentiation. Retinyl acetate also potentiated ornithine decarboxylase induction caused by phytohemagglutinin. Both of these retinoids augmented ornithine decarboxylase induction caused by phorbol 12-myristate 13-acetate. The half-life of ornithine decarboxylase activity estimated after addition of actinomycin D was longer in cells treated with phytohemagglutinin or phorbol 12-myristate 13-acetate together with retinoic acid than in cells treated with the mitogen alone. The half-life after addition of cycloheximide was not affected by retinoic acid. These results suggest that the retinoids are stimulators rather than inhibitors of ornithine decarboxylase induction caused by phytohemagglutinin or phorbol 12-myristate 13 acetate in guinea pig lymphocytes and that retinoic acid potentiates the enzyme activity at the transcriptional or posttranscriptional, but not at the post translational stage. PMID- 3091586 TI - Calcium binding to calmodulin. Cooperativity of the calcium-binding sites. AB - The effects of Mg2+ ion, pH, and KCl concentration on Ca2+ binding to calmodulin were studied by using a Ca2+ ion-sensitive electrode. The Ca2+ ion affinity of calmodulin increased with increasing pH or decreasing KCl concentration. Cooperativity between the Ca2+-binding sites was observed, and increased with decreasing pH or increasing KCl concentration. Free Ca2+ ion concentration was decreased by adding MgCl2 ion at low Mg2+ concentration and increased at higher concentrations in the presence of small amounts of Ca2+ ion. The decrease of free Ca2+ ion concentration by Mg2+ ion strongly suggests cooperativity between the Ca2+-binding sites, and it is difficult to explain the decrease in terms of the ordered binding models previously proposed. These results can be explained by a simple model which has four equivalent binding sites that bind Ca2+ and Mg2+ competitively, and showing cooperativity when either Ca2+ or Mg2+ is bound. Mg2+ ion binding to calmodulin was measured in the presence or absence of Ca2+ to confirm the validity of this model, and no Mg2+-specific site was observed. PMID- 3091588 TI - Immunological characterization of photosystem II chlorophyll-binding proteins from the cyanobacterium, Aphanocapsa 6714. AB - Chlorophyll-binding proteins from the cyanobacterium Aphanocapsa 6714 were identified by immunoblotting procedures. Three chlorophyll-binding complexes, CPIII', CPIIIa, and CPIIIb, were associated with PSII. CPIII' likely serves as an' antenna to PSII in Aphanocapsa since it could be removed from active PSII core preparations without loss of activity. The CPIII' proteins cross-reacted to antibodies prepared against the maize PSII light-harvesting complex, LHC-II. The CPIIIa polypeptides cross-reacted to antibodies raised against the Chlamydomonas PSII chlorophyll-proteins 5 and 6, indicating that this complex contains the major chlorophyll-binding species of the cyanobacterial PSII core. Lastly, an antibody prepared against the canobacterial 36-kDa chlorophyll-binding protein [Pakrasi, H., Riethman, H., and Sherman, L. (1985). Proc. Natl. Acad. Sci. USA 82, 6903-6907] recognized only the 36-kDa IIIb apoprotein, indicating that CPIIIb represents a distinct chlorophyll-protein complex. PMID- 3091590 TI - Kinetic mechanism of guinea pig neutrophil 5-lipoxygenase. AB - The kinetic mechanism of guinea pig neutrophil 5-lipoxygenase was investigated using a continuous spectrophotometric assay that monitors product diene formation at 236 nm due to substrate oxygenation. Progress curves for reactions with both arachidonic acid and eicosapentaenoic acid are characterized by 1-3-min lag phases in the attainment of steady-state velocities and product inhibition, as indicated by the total cessation of the reaction prior to complete depletion of substrate. The dependence of the steady-state velocity on arachidonic acid concentration appears to follow Michaelis-Menten kinetics, with Vmax = 4.2 +/- 0.4 nmol of 5-hydroxy-6,8,11,14-eicosatetraenoic acid/min/mg of protein and Ks = 25 +/- 4 microM. The addition of Ca2+ results in an overall activation: lag phases are shortened to 10-20 s, Vmax increases to 24 +/- 2 nmol/min/mg of protein, and Ks decreases to 7.7 +/- 1.7 microM; and a change in a mechanism to one involving substrate inhibition (Kss = 13 +/- 1 microM). The observed activation by Ca2+ has a half-maximal response at around 30 microM. In the presence of Ca2+, ATP causes an increase in Vmax to 30 +/- 4 nmol/min/mg of protein without changing Ks or Kss and a reduction of the lag to less than 5 s. The half-maximal response for ATP is 31 +/- 7 microM. Oxygenation of eicosapentaenoic acid in the presence of Ca2+ and ATP occurs with similar kinetics, except for significantly less substrate inhibition: Vmax = 31 +/- 6 nmol/min/mg of protein, Ks = 7 +/- 1 microM, and Kss = 33 +/- 2 microM. This is the first report suggesting a kinetic mechanism for 5-lipoxygenase, which accounts for substrate inhibition, regulation by Ca2+, and ATP and substrate specificity. PMID- 3091589 TI - Chemical modification and inactivation of rat liver microsomal cytochrome P-450c by 2-bromo-4'-nitroacetophenone. AB - The alkylating agent 2-bromo-4'-nitroacetophenone (BrNAP) binds covalently to each of 10 isozymes of purified rat liver microsomal cytochrome P-450 (P-450a-P 450j) but substantially inhibits the catalytic activity of only cytochrome P 450c. Regardless of pH, incubation time, presence of detergents, or concentration of BrNAP, treatment of cytochrome P-450c with BrNAP resulted in no more than 90% inhibition of catalytic activity. Alkylation with BrNAP did not cause the release of heme from the holoenzyme or alter the spectral properties of cytochrome P 450c, data that exclude the putative heme-binding cysteine, Cys-460, as the major site of alkylation. Two residues in cytochrome P-450c reacted rapidly with BrNAP, for which reason maximal loss of catalytic activity was invariably associated with the incorporation of approximately 1.5 mol of BrNAP/mol of cytochrome P 450c. Two major radio-labeled peptides were isolated from a tryptic digest of [14C]BrNAP-treated cytochrome P-450c by reverse-phase high performance liquid chromatography. The amino acid sequence of each peptide was determined by microsequence analysis, but the identification of the residues alkylated by BrNAP was complicated by the tendency of the adducts to decompose when subjected to automated Edman degradation. However, results of competitive binding experiments with the sulfhydryl reagent 4,4'-dithiodipyridine identified Cys-292 as the major site of alkylation and Cys-160 as the minor site of alkylation by BrNAP in cytochrome P-450c. PMID- 3091591 TI - Direct evidence for involvement of a guanine nucleotide-binding protein in chemotactic peptide-stimulated formation of inositol bisphosphate and trisphosphate in differentiated human leukemic (HL-60) cells. Reconstitution with Gi or Go of the plasma membranes ADP-ribosylated by pertussis toxin. AB - fMet-Leu-Phe (fMLP) stimulated the formation of inositol bis- and trisphosphate in the [3H]inositol-labeled plasma membranes from the human leukemic (HL-60) cells differentiated to neutrophil-like cells by dibutyryl cyclic AMP. The stimulatory effect of fMLP was completely dependent on the simultaneous presence of GTP and Ca2+. The fMLP-stimulated formation of the phosphorylated inositols was markedly reduced by the prior ADP-ribosylation of the membranes with pertussis toxin. This toxin ADP-ribosylated a Mr approximately 40,000 protein, presumably the alpha subunit of Gi and/or Go, in the membranes. Reconstitution of the membranes ADP-ribosylated by pertussis toxin with Gi or Go purified from rat brain restored the fMLP-stimulated formation of the phosphorylated inositols. The efficiency of the rat brain Gi and Go in this capacity was roughly equal. The rat brain Gi or Go ADP-ribosylated beforehand by pertussis toxin was inactive in this reconstitution. These results indicate that both rat brain Gi and Go have the potency to couple functionally the fMLP receptor to the phospholipase C-mediated polyphosphoinositide hydrolysis and suggest that Gi or Go may be involved in the mechanism of signal transduction from the fMLP receptor to this reaction in the differentiated HL-60 cells. PMID- 3091592 TI - Release of arachidonate and reduction of oxygen. Independent metabolic bursts of the mouse peritoneal macrophage. AB - Diverse particulate and soluble stimuli trigger two metabolic bursts in mouse peritoneal macrophages important in the inflammatory and/or cytotoxic actions of the cells: release, oxygenation, and further metabolism of arachidonic acid from endogenous phospholipids and reduction of molecular oxygen to reactive intermediates. We tested the hypothesis that the release of arachidonic acid or formation of its metabolites are obligatory intermediate steps in triggering the NADPH oxidase that reduces O2 to O-2. With phorbol diesters as stimuli, the following inhibitors of phospholipase A2 and lipoxygenase suppressed release of H2O2 at nontoxic concentrations (microM range): p-bromophenacyl bromide, quinacrine, eicosatetraenoic acid, nordihydroguaiaretic acid, and phenidone. Indomethacin and acetylsalicylic acid were ineffective. However, the suppressive effect of the first five agents on H2O2 release could be attributed to their suppression of macrophage glucose uptake at the same concentrations, a previously unrecognized effect of these compounds. Further, concanavalin A, wheat germ agglutinin, and thrombin each stimulated abundant arachidonate release without H2O2 release. Finally, noncytolytic concentrations of cycloheximide and/or emetine suppressed arachidonate release without affecting H2O2 secretion triggered either by phorbol esters or zymosan. Release and metabolism of arachidonic acid and secretion of reactive oxygen intermediates appear to be two frequently coincident but mutually independent metabolic pathways in the mouse peritoneal macrophage. PMID- 3091593 TI - Expression of human malaria parasite purine nucleoside phosphorylase in host enzyme-deficient erythrocyte culture. Enzyme characterization and identification of novel inhibitors. AB - The intraerythrocytic human malaria parasite, Plasmodium falciparum, requires a source of hypoxanthine for nucleic acid synthesis and energy metabolism. Adenosine has been implicated as a major source for intraerythrocytic hypoxanthine production via deamination and phosphorolysis, utilizing adenosine deaminase and purine nucleoside phosphorylase, respectively. To study the expression and characteristics of human malaria purine nucleoside phosphorylase, P. falciparum was successfully cultured in purine nucleoside phosphorylase deficient human erythrocytes to an 8% parasitemia level. Purine nucleoside phosphorylase activity was undetectable in the uninfected enzyme-deficient host red cells but after parasite infection rose to 1.5% of normal erythrocyte levels. The parasite purine nucleoside phosphorylase was not cross-reactive with antibody against human enzyme, exhibited a calculated native molecular weight of 147,000, and showed a single major electrophoretic form of pI 5.4 and substrate specificity for inosine, guanosine and deoxyguanosine but not xanthosine or adenosine. The Km values for substrates, inosine and guanosine, were 4-fold lower than that for the human erythrocyte enzyme. In these studies we have identified two novel potent inhibitors of both human erythrocyte and parasite purine nucleoside phosphorylase, 8-amino-5'-deoxy-5'-chloroguanosine and 8-amino-9 benzylguanine. These enzyme inhibitors may have some antimalarial potential by limiting hypoxanthine production in the parasite-infected erythrocyte. PMID- 3091595 TI - Transfer of glycerol by Endo-beta-N-acetylglucosaminidase F to oligosaccharides during chitobiose core cleavage. AB - N-Linked oligosaccharides, when hydrolyzed by glycerol-containing preparations of endo-beta-N-acetylglucosaminidase (Endo) F from Flavobacterium meningosepticum were found to have glycerol attached to their reducing ends. The absence of a reducing end was confirmed by high-field 1H NMR spectroscopy, and the incorporated glycerol was verified through mass spectrometry and collisionally activated decomposition fast atom bombardment/mass spectrometry/mass spectrometry techniques. Periodate oxidation of [1(3)-14C]glycerol-labeled oligosaccharides indicated glycerol was glycosidically linked via its 1(3) carbon to the C1 of the reducing end N-acetylglucosamine. In a second, less favored reaction, the glycerol glycoside was hydrolyzed by Endo F using water as the terminal nucleophile, thus regenerating the N-acetylglucosamine reducing end. Glycerol could be removed from Endo F preparations without affecting enzyme stability, and chitobiosyl core hydrolysis in its absence provided intact oligosaccharides with normal N-acetylglucosamine reducing ends. The incorporation of labeled glycerol may provide a useful method for monitoring of Endo F release of oligosaccharides. PMID- 3091594 TI - Spermidine N1-acetyltransferase has a larger role than ornithine decarboxylase in 1 alpha,25-dihydroxyvitamin D3-induced putrescine synthesis. AB - We have reported that a single injection of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3), the active form of vitamin D3, into vitamin D-deficient chicks produces a marked increase in the formation of duodenal putrescine by two pathways, one from ornithine and one from spermidine (Shinki, T., Takahashi, N., Kadofuku, T., Sato, T., and Suda, T. (1985) J. Biol. Chem. 260, 2185-2190). In this work, the conversion of [3H]ornithine into [3H]putrescine catalyzed by ornithine decarboxylase was compared with the conversion of [14C]spermidine into [14C]putrescine catalyzed by spermidine N1-acetyltransferase and polyamine oxidase. Using the in situ duodenal loop method in the presence or absence of alpha-difluoromethylornithine, we evaluated the relative contributions of these two pathways in the 1 alpha,25(OH)2D3-induced duodenal synthesis of putrescine. Prior administration of alpha-difluoromethylornithine inhibited neither the 1 alpha,25(OH)2D3-induced increase in duodenal spermidine N1-acetyltransferase activity nor the vitamin-induced enhancement of the duodenal putrescine content, although it completely suppressed the duodenal ornithine decarboxylase activity induced by 1 alpha,25(OH)2D3. The duodenal content of spermidine decreased time dependently after injection of 1 alpha,25(OH)2D3. The increase of duodenal putrescine by 1 alpha,25(OH)2D3 coincided quantitatively with the amount of putrescine synthesized from spermidine but not from ornithine after injection of the vitamin. These unexpected results clearly indicate that spermidine N1 acetyltransferase has a larger role than ornithine decarboxylase in the increase of duodenal putrescine synthesis induced by 1 alpha,25(OH)2D3. The polyamine metabolism reported here may be related to the characteristics of intestinal epithelial cells such as the short lifetime (90-108 h) and typical gradient of differentiation from the crypt to villus regions. PMID- 3091596 TI - Nature of the enhancement of lecithin-cholesterol acyltransferase reaction by various apolipoproteins. AB - The effects of human apolipoproteins on the lecithin-cholesterol acyltransferase reaction were studied by using purified human lecithin-cholesterol acyltransferase and phosphatidylcholine-cholesterol vesicles. When the assay mixtures contained an optimal amount or excess of apo-A-I, the addition of apo-A II, apo-C-II, apo-C-III1, or apo-C-III2 inhibited the enzymatic reaction. However, at suboptimal apo-A-I concentrations, the addition of low concentrations of these apolipoproteins exhibited activating effects. The relative activating effects were greater at lower apo-A-I levels. Under no circumstance did the combined activating effect of apo-A-I and other apolipoproteins exceed the maximum activating effect observed with the optimal level of apo-A-I alone. Since apo-A-II, apo-C-II, and apo-C-III did not show significant activating effects in the absence of apo-A-I, these apolipoproteins apparently did not act as true activator proteins for the enzymatic reaction. The activation of the enzymatic reaction by apo-A-I alone was shown to be due in part to the enhancement of the enzyme transfer between the substrate particles. The replacement of the transfer enhancing effect of apo-A-I by apo-A-II, apo-C-II, or apo-C-III appears to be responsible for their apparent activating effects in the presence of suboptimal levels of apo-A-I. These apolipoproteins seemed to coexist with both the enzyme and apo-A-I on the substrate particles under the conditions when they showed the activating effect. However, at the concentrations inhibitory to the enzymatic reaction, these apolipoproteins displaced both the enzyme and apo-A-I from the phosphatidylcholine-cholesterol vesicles. PMID- 3091598 TI - Purification and properties of aminoacetone synthetase from beef liver mitochondria. AB - Aminoacetone synthetase from beef liver mitochondria was purified to homogeneity and shown to be a member of the pyridoxal 5'-phosphate-dependent family of enzymes. This enzyme catalyzes the condensation of glycine and acetyl-CoA to produce CO2, CoA, and the stable product aminoacetone. Bovine aminoacetone synthetase is a dimer (Mr 56,000) of identical subunits and contains 2 mol of pyridoxal phosphate/mol of dimer. The holoenzyme was resolved by dialysis against cysteine and has a pI of 5.2. The holoenzyme shows an absorption maximum at 428 nm which undergoes a shift to 335 nm when reduced with sodium borohydride. The Km values of glycine and acetyl-CoA were 22 mM and 53 microM, respectively. Initial velocity studies indicate that the condensation reaction proceeds by an ordered mechanism. With the exception of aminomalonate, bovine aminoacetone synthetase acts specifically on glycine and acetyl-CoA. Coupled reactions of purified bovine aminoacetone synthetase and porcine L-threonine dehydrogenase demonstrated the interconversion of threonine and glycine. PMID- 3091597 TI - Selective inhibition of collagen synthesis by the Ca2+ ionophore A23187 in cultured human fibroblasts. AB - The question of whether the Ca2+ ionophore A23187 affects collagen production relative to total protein synthesis or has possible effects on collagen degradation was investigated. Cultured normal human fibroblasts were incubated with radioactive proline, and the radioactivity of collagenase-sensitive and resistant proteins was used to calculate the rates of protein production. The net production of collagen relative to total proteins was inhibited by A23187 in a dose-related manner, and 50% inhibition of basal collagen production was achieved with 0.6 microM A23187. There was a 70% decrease in the absolute rate of collagen production in the presence of 0.6 microM A23187 which represented a 4-fold greater inhibition of collagen production than of noncollagen protein production. The major mechanism for the decreased net production of collagen was decreased synthesis, rather than increased degradation. Ca2+ mobilization induced by cholecystokinin octapeptide was also associated with selective inhibition of collagen production in normal human fibroblasts. These studies establish that the Ca2+ ionophore A23187 induces a selective decrease in collagen polypeptide synthesis by normal human fibroblasts and suggest a modulatory role of Ca2+ on collagen metabolism. PMID- 3091599 TI - Effects of the binding of myosin light chain kinase on the reactivities of calmodulin lysines. AB - The effects of the binding of smooth muscle myosin light chain (MLC) kinase on the microenvironments of different regions of calmodulin (CaM) were investigated by comparing the acylation rate constants of the seven lysine amino groups of free CaM with those of CaM complexed with MLC kinase. Equimolar amounts of CaM and CaM-MLC kinase complex were trace labeled with [3H]acetic anhydride in the presence of phenylalanine as a standard nucleophile. After completion of the reaction, equal amounts of a trace 14C-acetylated CaM sample, together with [14C]acetylphenylalanine, were added to each reaction mixture. The 3H/14C-labeled CaM and acetylphenylalanine were then isolated from each solution. After complete reaction with nonradioactive acetylating reagent, 3H/14C ratios (r) were determined for each epsilon-N-acetyllysine in the two CaM samples. These values were obtained either from isolated peptide fragments containing one lysine or from epsilon-N-acetyl phenylthiohydantoin lysine obtained by Edman degradation of peptide fragments containing two lysines. From the ratios, protection factors (= rfree/rcomplex) were determined as a measure of the perturbation produced by MLC kinase binding. These protection factors were corrected, using the isotope ratios of the internal standard, for differences in the degree of competition for labeling reagent between the two mixtures. In two separate labeling experiments employing different levels of trace labeling, very little change was observed in the reactivities of four lysines on MLC kinase binding (lysines 13, 30, 77, and 94). Small but reproducible decreases (about 2-fold) were observed in the reactivities of lysines 21 and 148, while lysine 75 underwent a major (more then 7-fold) decrease in labeling. In conjunction with previously published data, these results are interpreted as suggesting that the major perturbation in lysine 75 is a direct effect of MLC kinase contact with CaM and that a region in the central helix containing this residue, but not lysine 77, represents or is near the CaM-binding site for MLC kinase. The smaller changes in reactivities at lysines 21 and 148 may reflect a conformational change that occurs in CaM as a result of binding to MLC kinase. PMID- 3091600 TI - Purification and characterization of 5'-deoxy-5'-methylthioadenosine phosphorylase from human placenta. AB - 5'-Methylthioadenosine phosphorylase has been purified to homogeneity (30,000 fold) from human full-term placenta by a procedure involving covalent chromatography on organomercurial-agarose as the major step. The specific activity of the homogeneous enzyme is 10.2 mumol of 5'-methylthioadenosine cleaved per min per mg of protein, and the overall yield is about 20%. The enzyme has a molecular weight of 98,000, as determined by gel filtration on Sephacryl S 200 and Superose 6B, and is composed by three apparently identical subunits with a molecular weight of 32,500. The isoelectric point is 5.5, and the optimal pH ranges from 7.2 to 7.6. The resistance of the enzyme to thermal inactivation is increased remarkably by the addition of 5'-methylthioadenosine or phosphate. The homogeneous enzyme shows an absolute requirement for -SH-reducing agents and is specifically and rapidly inactivated by thiol-blocking compounds. The reaction catalyzed by the enzyme is fully reversible with a Keq of 1.39 X 10(-2) (in the direction of phosphorolysis) at 37 degrees C and pH 7.4. The Km values for 5' methylthioadenosine, phosphate, adenine, and 5-methylthioribose 1-phosphate are 5, 320, 23, and 8 microM, respectively. PMID- 3091601 TI - Crystallization and preliminary diffraction studies of the Lys-49 phospholipase A2 from Agkistrodon piscivorus piscivorus. AB - Previous chemical and structural studies have proposed a major role for Asp-49 in the calcium-mediated activation of phospholipases A2. Recently, a new class of phospholipases A2 has been characterized with a lysine in the place of aspartate at position 49 (Maraganore, J. M., Merutka, G., Cho, W., Welches, W., Kezdy, F. J., and Heinrikson, R. L. (1984) J. Biol. Chem. 259, 13839-13843; Maraganore, J. M., and Heinrikson, R. L. (1986) J. Biol. Chem. 261, 4797-4804). Although both the Lys-49 and Asp-49 phospholipases require calcium for enzymatic activity, the Lys-49 enzymes appear to be unique in their ability to bind phospholipids prior to undergoing calcium-mediated activation. We have successfully crystallized the Lys-49 phospholipase A2 from the venom of the American cottonmouth water moccasin (Agkistrodon piscivorus piscivorus). The crystals are tetragonal, the space group being P4(1)2(1)2 or P4(3)2(1)2 with unit cell dimensions of a = b = 71.05 A, and c = 57.76 A. There is only one molecule in the asymmetric unit and the crystals provide good quality diffraction data to 2.2 A. PMID- 3091602 TI - Structure and antigenicity of the phosphorylated lipopolysaccharide antigens from the leprosy and tubercle bacilli. AB - A family of major arabinose- and mannose-containing phosphorylated lipopolysaccharides was isolated from Mycobacterium leprae and Mycobacterium tuberculosis. The only antigenic member of the family, lipoarabinomannan (LAM)-B, was purified by anion exchange and gel filtration chromatography in detergent and recovered in large quantities (15 mg/g of bacteria). It yielded a broad diffuse band on polyacrylamide gel electrophoresis but appeared homogeneous by this criterion and gel filtration. Besides arabinose and mannose, it contained glycerol and a polyol phosphate and was acylated by lactate, succinate, palmitate, and 10-methyloctadecanoate. The phosphate was released by alkalinolysis and identified by thin layer chromatography and gas chromatography mass spectrometry as myoinositol 1-phosphate. Thus, the group-specific "arabinomannan" of the genus Mycobacterium in the native state is acylated, contains the substituents of phosphatidylinositol, and is apparently membrane associated. LAM-B is one of the dominant immunogens of the leprosy bacillus reacting readily with antibodies from lepromatous leprosy patients and monoclonal antibodies in plate and nitrocellulose enzyme-linked immunosorbent assay and on electrophoretic immunoblots. It is immunologically cross-reactive with a like product from M. tuberculosis. LAM-B is clearly the pervasive "glycoprotein" antigen of the leprosy bacillus and may be the long sought lipoteichoic acid-like polymer of Mycobacterium with a role in cell wall physiology, macrophage recognition, and perhaps an involvement in cross-protective immunity. PMID- 3091603 TI - Simultaneous sulfation of endogenous chondroitin sulfate and chondroitin-derived oligosaccharides. Studies with separate 4-sulfating and 6-sulfating microsomal systems. AB - Microsomal preparations from chondroitin 6-sulfate-producing chick embryo epiphyseal cartilage and from chondroitin 4-sulfate-producing mouse mastocytoma cells were incubated with varying concentrations of 3' phosphoadenylylphospho[35S]sulfate and chondroitin hexasaccharide in the presence or absence of Triton X-100. [35S]Sulfate incorporation into hexasaccharide and into endogenous microsomal chondroitin 6-sulfate or endogenous microsomal chondroitin 4-sulfate was measured. With both microsomal systems, Triton X-100 increased the incorporation of [35S]sulfate into hexasaccharide but had much less effect on the incorporation into endogenous chondroitin sulfate. Higher concentrations of hexasaccharide inhibited the incorporation of [35S]sulfate into endogenous chondroitin sulfate. The apparent Km for 3' phosphoadenylylphosphosulfate for both the 6-sulfotransferase and 4 sulfotransferase with hexasaccharide and with endogenous chondroitin sulfate in the presence or absence of Triton X-100 were all similar. However, the apparent Km for hexasaccharide was lower in the presence of Triton X-100 for both the microsomal sulfotransferases. This is consistent with solubilization of sulfotransferases, and indicates that hexasaccharide access to these enzymes had been limited in the particulate system. Examination of 35S-oligosaccharide products formed with each system demonstrated good 6-sulfation or 4-sulfation of penultimate GalNAc at the non-reducing end of the chondroitin hexasaccharide. However, no 6-sulfation of terminal GalNAc at the non-reducing end of a chondroitin pentasaccharide derived from hexasaccharide was observed, and there was only minimal 4-sulfation of this terminal GalNAc. Concurrent addition of GalNAc to hexasaccharide resulting in heptasaccharide did not appear to promote significant 6-sulfation or 4-sulfation of newly added non-reducing terminal GalNAc. PMID- 3091604 TI - Purification and characterization of a novel inhibitor of urokinase from human urine. Quantitation and preliminary characterization in plasma. AB - Urokinase-related proteins in human urine occur mainly as a 1:1 complex of urokinase with an inhibitor (Stump, D. C., Thienpont, M., and Collen, D. (1986) J. Biol. Chem. 261, 1267-1273). BALB/c mice were immunized with this urokinase urokinase inhibitor complex and spleen cells fused with mouse myeloma cells, resulting in hybridomas producing monoclonal antibodies. Three antibodies reacting with the complex but not with urokinase were utilized to develop a sensitive (0.5 ng/ml) enzyme-linked immunosorbent assay for the urokinase inhibitor, which was used for monitoring its purification by chromatography on zinc chelate-Sepharose, concanavalin A-Sepharose, SP-Sephadex C-50, and Sephadex G-100. A homogenous glycoprotein of apparent Mr 50,000 was obtained with a yield of 40 micrograms/liter urine and a purification factor of 320. One mg of the purified protein inhibited 35,000 IU of urokinase within 30 min at 37 degrees C. This protein was immunologically related to both the purified urokinase-urokinase inhibitor complex and to the inhibitor portion dissociated from it by nucleophilic dissociation. It was immunologically distinct from all known protease inhibitors, including the endothelial cell-derived fast-acting inhibitor of tissue-type plasminogen activator, the placental inhibitor of urokinase and protease nexin. In electrophoresis the protein migrated with beta-mobility. Inhibition of urokinase occurred with a second order rate constant (k) of 8 X 10(3) M-1 s-1 in the absence and of 9 X 10(4) M-1 s-1 in the presence of 50 IU of heparin/ml. The urokinase inhibitor was inactive towards single-chain urokinase type plasminogen activator and plasmin, but it inhibited two-chain tissue-type plasminogen activator with a k below 10(3) M-1 s-1 and thrombin with a k of 4 X 10(4) M-1 s-1 in the absence and 2 X 10(5) M-1 s-1 in the presence of heparin. The concentration of this urokinase inhibitor in plasma from normal subjects determined by immunoassay was 2 +/- 0.7 micrograms/ml (mean +/- S.D., n = 25). The protein purified from plasma by immunoabsorption had the same Mr, amino acid composition, and immunoreactivity as the urinary protein. Furthermore, when urokinase was added to plasma, time-dependent urokinase-urokinase inhibitor complex formation was observed at a rate similar to that observed for the inhibition of urokinase by the purified inhibitor from urine. This urokinase inhibitor, purified from human urine, most probably represents a new plasma protease inhibitor. PMID- 3091605 TI - Purification and characterization of the reconstitutively active phosphate transporter from rat liver mitochondria. AB - Procedures have been developed for the purification of a nearly homogeneous, highly active phosphate transport system from rat liver mitochondria in either a two-subunit (alpha, beta) or a single subunit (beta) form. Significantly, both forms display a similar high magnitude N-ethylmaleimide (NEM)-sensitive Pi/Pi exchange activity upon incorporation into phospholipid vesicles. The transport system is extracted from hypotonically shocked mitoplasts with Triton X-114 and purified in the presence of cardiolipin by sequential chromatography on hydroxylapatite, DEAE-Sepharose CL-6B, and Affi-Gel 501. Depending on the conditions used to elute the transporter from Affi-Gel 501, preparations are obtained which, when analyzed by high resolution sodium dodecyl sulfate polyacrylamide gradient gel electrophoresis, consist of either a single 33-kDa protein (beta) or a 33-kDa (beta) plus a 35-kDa (alpha) component. In preparations yielding the latter result, both bands display a nearly equivalent Coomassie staining intensity. Furthermore, after alkylation with NEM, the two protein bands co-migrate. Fluorography indicates that the coalesced band contains [3H]NEM. Upon reconstitution of the purified Pi carrier into liposomes, direct measurement of both the initial transport rate and the amount of protein that actually incorporates into the phospholipid vesicles yields a specific transport activity of 22.6 mumol/min/mg of protein. The exchange is characterized by a first order rate constant of 0.85 min-1, a t1/2 of 49 s, and is inhibited by sulfhydryl reagents (i.e., NEM, p-chloromercuribenzoate, and mersalyl). It is also substantially inhibited by diethyl pyrocarbonate, N-acetylimidazole, phenylglyoxal, and 5-dimethylaminoaphthalene-1-sulfonyl chloride. In addition to providing a simple, rapid method for preparing the NEM-sensitive phosphate carrier in nearly homogeneous form, these studies provide new information about the catalytically active species of the carrier, its kinetic properties, and its inhibitor sensitivities. PMID- 3091606 TI - Purification and characterization of a senile amyloid-related antigenic substance (apoSASSAM) from mouse serum. apoSASSAM is an apoA-II apolipoprotein of mouse high density lipoproteins. AB - Two putative serum precursors which cross-react with antiserum against murine senile amyloid protein (ASSAM) were isolated from the high density lipoprotein (HDL) of normal mouse serum. Apolipoproteins designated "apoSASSAM-1" and "apoSASSAM-2" have the same molecular weight as tissue amyloid fibril protein. ApoSASSAM-1 and apoSASSAM-2 migrate to an intermediate position between apoA-I and apoC on alkaline-urea polyacrylamide gel electrophoresis and are present mainly in HDL apoproteins and to a slight extent in very low density lipoprotein apoproteins when compared to apoC. ApoSASSAM-1 and apoSASSAM-2 are polymorphic; there are two apparent isoproteins of apoSASSAM-1 with isoelectric points of 4.72 and 4.79 and two major isoproteins of apo-SASSAM-2. Subunit bands of ASSAM separated by alkaline-urea polyacrylamide gel electrophoresis and that migrated to the same positions as apoSASSAM-1 and apoSASSAM-2 were labeled by anti apoSASSAM-1 antiserum. The amino acid compositions of apoSASSAM-1 and apoSASSAM-2 were much the same and closely resembled those of ASSAM and mouse apoA-II. Sequence analysis of apoSASSAM and ASSAM revealed a blocked amino terminus. ApoSASSAM is considered to be a mouse apoA-II and probably transforms to amyloid fibril "ASSAM" in tissues through a process yet to be clarified. PMID- 3091607 TI - Changes in eIF-4D hypusine modification or abundance are not correlated with translational repression in HeLa cells. AB - Initiation factor eIF-4D is represented by about 11 X 10(6) molecules/HeLa cell (0.45% of the cytoplasmic protein molecules). The fraction of eIF-4D that contains the post-translational modification of lysine converted to hypusine is not regulated with respect to translation rate in HeLa cells. It is proportional to the rate of eIF-4D synthesis in exponentially growing cells (maximal protein synthesis rates) as well as in serum-depleted cells (protein synthesis rates depressed about 6-8-fold). In cells in which protein synthesis is arrested by cycloheximide, no hypusine addition or exchange is detected. During rapid repressions of protein synthesis due to either heat shock or hypertonic shock there is no change in the extent of eIF-4D containing hypusine. These results are most consistent with an eIF-4D biogenesis in which all molecules are modified to contain hypusine during or shortly after the translation process itself, and the modification state is not regulated thereafter. PMID- 3091609 TI - Inter-relation of cell adhesion and differentiation in Dictyostelium discoideum. PMID- 3091608 TI - Identification of a MAP 2-like ATP-binding protein associated with axoplasmic vesicles that translocate on isolated microtubules. AB - Axoplasmic vesicles were purified and observed to translocate on isolated microtubules in an ATP-dependent, trypsin-sensitive manner, implying that ATP binding polypeptides essential for force generation were present on the vesicle surface. To identify these proteins [alpha 32P]8-azidoadenosine 5'-triphosphate ([alpha 32P]8-N3ATP), a photoaffinity analogue of ATP, was used. The results presented here identify and characterize a vesicle-associated polypeptide having a relative molecular mass of 292 kD that bound [alpha 32P]8-N3ATP. The incorporation of label is ultraviolet light-dependent and ATP-sensitive. Moreover, the 292-kD polypeptide could be isolated in association with vesicles or microtubules, depending on the conditions used, and the data indicate that the 292-kD polypeptide is similar to mammalian brain microtubule-associated protein 2 (MAP 2) for the following reasons: The 292-kD polypeptide isolated from either squid axoplasm or optic lobe cross-reacts with antiserum to porcine brain MAP 2. Furthermore, it purifies with taxol-stabilized microtubules and is released with salt. Based on these characteristics, the 292-kD polypeptide is distinct from the known force-generating molecules myosin and flagellar dynein, as well as the 110 130-kD kinesin-like polypeptides that have recently been described (Brady, S. T., 1985, Nature (Lond.), 317:73-75; Vale, R. D., T. S. Reese, and M. P. Sheetz, 1985b, Cell, 42:39-50; Scholey, J. M., M. E. Porter, P. M. Grissom, and J. R. McIntosh, 1985, Nature (Lond.), 318:483-486). Because the 292-kD polypeptide binds ATP and is associated with vesicles that translocate on purified MAP-free microtubules in an ATP-dependent fashion, it is therefore believed to be involved in vesicle-microtubule interactions that promote organelle motility. PMID- 3091610 TI - The molecular genetics of haemophilia A and B. PMID- 3091611 TI - [Attempt at cost evaluation of the prevention of parietal infection in abdominal surgery. Retrospective study of 1100 patients surgically treated over 4 years]. AB - Justification for prevention of parietal infection in abdominal surgery was evaluated by a retrospective study of 1100 patients operated upon between 1981 and 1984. Rate of infection in class I was 0.5% and in class IV 8%. Comparison of costs of prevention, and of treatment of declared infection, demonstrated a sum of 280 French francs per case, this representing the allowed outlay in this field. Preventive measures should continue to be applied, this type of expenditure being perfectly justified by the economy obtained through shortening of hospital stay and the inestimable improvement in patients' comfort. PMID- 3091612 TI - Justice Department opinion on AIDS: another example of insensitivity. PMID- 3091613 TI - Toxic megacolon in ulcerative colitis. Early diagnosis and management. AB - The diagnosis of toxic megacolon is based on a thorough history and physical examination, simple laboratory tests, and careful examination of plain abdominal films. As with other uncommon conditions, making the correct diagnosis requires a high index of suspicion. This is especially true when toxic megacolon is the initial manifestation of ulcerative colitis. In this setting, a previous history of chronic diarrhea may be lacking. Patients with toxic megacolon are usually first seen in the emergency room, so the diagnosis must be entertained in all patients presenting with abdominal distention and acute or chronic diarrhea. The diagnosis of toxic megacolon does not require CT scans, ultrasound examinations, radionuclide scans, colonoscopy, or barium enema. In fact, reliance on those nonessential diagnostic procedures may delay diagnosis while the patient continues to deteriorate. Once toxic megacolon is diagnosed, the patient should be admitted immediately to an intensive care unit for careful monitoring by both medical and surgical staff. PMID- 3091615 TI - IV streptokinase: when and for whom? PMID- 3091614 TI - The cocaine user who looked like a bullfrog. PMID- 3091616 TI - Immunization for Td and Rocky Mt. spotted fever. PMID- 3091617 TI - Molecular biologic diagnosis of the hemoglobinopathies. PMID- 3091618 TI - An infectious mass presenting as a tumor. PMID- 3091619 TI - Persistent vomiting after vigorous football game. PMID- 3091620 TI - Hyperthyroidism in a healthy pregnant woman. PMID- 3091621 TI - A sub-Q heroin and cocaine addict with chills, fever, and trismus. PMID- 3091622 TI - Deep T-wave inversion: which coronary artery is involved? PMID- 3091623 TI - Synovial inflammation in rheumatoid arthritis. PMID- 3091624 TI - A 3-year course of GI and CNS symptoms. PMID- 3091625 TI - A defective detective. PMID- 3091626 TI - Determination of Ro 14-1761, a new third-generation cephalosporin, in the plasma and milk of cattle by column switching high-performance liquid chromatography. AB - A sensitive and specific high-performance liquid chromatographic procedure was developed for the determination of the third-generation cephalosporin Ro 14-1761 in cow plasma and milk. The molecular structure of the new antimicrobial was very close to that of ceftriaxone, but the high-performance liquid chromatographic methods available for the latter could not be used as Ro 14-1761 adsorbed and/or degraded during the chromatographic process. Furthermore, the high-performance liquid chromatographic technique derived for ceftriaxone was not sensitive enough for our purposes. In the new assay, the plasma (milk) protein was precipitated with acetonitrile after dilution of the sample with water. For low concentrations (less than or equal to 10 micrograms/ml), the supernatant obtained after centrifugation was concentrated by extracting acetonitrile with methylene chloride. Quantification was performed by column switching high-performance liquid chromatography with UV detection (274 nm) using ion-pair reversed-phase chromatography. Ethylenediaminotetraacetic sodium salt had to be added to the mobile phase (1.2 mM) to prevent adsorption and/or degradation of the cephalosporin on the analytical column. The selectivity of the chromatographic separation was enhanced by heating the column to ca. 50 degrees C. The drug recovery was better than 85%. The limit for quantitative determination in both milk and plasma was 0.1 microgram of Ro 14-1761 per millilitre with an accuracy of 1% (coefficient of variation 10%). The overall accuracy and precision were 1 10% in the 0.1-100 micrograms/ml concentration range. PMID- 3091627 TI - Nocturnal continuous infusion of growth hormone (GH)-releasing hormone results in a dose-dependent accentuation of episodic GH secretion in normal men. AB - Fluctuations in plasma GH levels have been found in patients with acromegaly who have continuously elevated levels of ectopically produced GH-releasing hormone (GHRH). Likewise, plasma GH fluctuations have been found in normal subjects receiving continuous GHRH infusions. We report the effects of two doses of GHRH, administered by constant infusion, on nocturnal GH secretion in six normal young men. Each received, in random order, 2.5 ng/kg X min GHRH, 15 ng/kg X min GHRH, and 0.15 M NaCl. During both GHRH doses, a highly significant increase in total nocturnal GH secretion was found (P less than 0.001) as well as an increase in GH secretion during different periods of the night. Nocturnal GH secretion was episodic during the GHRH infusions, with an increase in the number and magnitude of the peaks compared to those during the NaCl infusion. Plasma immunoreactive GHRH concentrations plateaued at 1 h during the high dose and at 3 h during the low dose GHRH infusion. Sleep parameters, including total sleep time, sleep latency, and duration and timing of the different sleep stages, were not affected by GHRH infusions. We conclude that GHRH, continuously infused, increases nocturnal GH secretion according to the dose, while the episodic pattern of GH secretion is maintained. PMID- 3091628 TI - Sustained rises in serum thyrotropin, thyroxine, and triiodothyronine during long term, continuous thyrotropin-releasing hormone treatment in patients with amyotrophic lateral sclerosis. AB - In a pilot therapeutic trial, four patients with amyotrophic lateral sclerosis (ALS) were treated with long term, continuous infusions of TRH, three intrathecally and one epidurally. They had prompt increases in serum TSH and thyroid hormone concentrations, averaging 120% for TSH, 49% for serum T4, 68% for the serum free T4 index, 49% for serum T3, and 67% for the serum free T3 index. These elevations were statistically significant for all but serum T3 and persisted for the duration of treatment (4-7 months). Mean values during treatment were near the upper limit of normal for each of these hormone measurements. After TRH withdrawal, serum TSH fell transiently below the normal range. A comparison group of four patients with ALS treated by twice weekly intrathecal bolus doses of TRH had no significant changes in serum TSH, T4, or T3. During continuous TRH treatment, the responsiveness of both TSH and PRL to a standard iv TRH stimulation test was blunted, but not abolished. Basal serum PRL was occasionally elevated in the two women during continuous TRH treatment, but was normal in the men, and serum GH was normal in all patients. In the patients receiving continuous TRH treatment, indexes of end-organ effects of thyroid hormone were inconclusive; none had a rise in serum ferritin, one of four had a rise in serum sex hormone-binding globulin, and three had increased creatinuria. These results provide direct evidence in man that chronic TRH administration can cause modest sustained increases in serum TSH and thyroid hormones, though the metabolic consequences of these changes are uncertain, and appears to raise the set-point of the pituitary-thyroid axis, i.e. the serum T4 and T3 concentrations needed for a given degree of suppression of basal TSH secretion. PMID- 3091629 TI - The effect of pulsatile administration, continuous infusion, and diurnal variation on the growth hormone (GH) response to GH-releasing hormone in normal men. AB - To examine the relative effectiveness of GH-releasing hormone (GHRH) given either as multiple iv pulses or as a continuous iv infusion, we studied the GH response to a nearly equivalent total dose of GHRH-44 administered by both routes in a group of normal men. Further, in view of the pulsatile nature of GH secretion and its augmentation with sleep, we investigated whether a diurnal difference in GH release was present during chronic pulsatile administration of GHRH during day and night. Seven men received six GHRH pulses (1 microgram/kg, iv) at 2-h intervals during both day (0900-2100 h) and night (2100-0900 h), and four underwent nighttime placebo pulsing. Eight men received a daytime continuous GHRH infusion (0.15 microgram/kg X h for 5 h, followed by 0.75 microgram/kg X h for 5 h) and a separate 10-h placebo infusion. The GH response to a bolus dose of GHRH (1 microgram/kg, iv) was determined after both continuous GHRH and placebo infusions. No significant difference was found in the GH area response (mean +/- SEM) during total day and night GHRH pulsing periods (6095 +/- 1192 vs. 6506 +/- 1483 ng/min X ml; P = NS). GH secretion was blunted after the initial daytime GHRH pulse (P = 0.02), and only two of seven men had a GH increase after the second pulse; responsiveness was restored after the fourth pulse. In contrast, all subjects responded to the second nighttime GHRH pulse. During continuous GHRH infusions, GH secretion was unsustained and pulsatile. The incremental GH response to a single GHRH bolus dose was decreased after GHRH infusion compared to that after placebo (4.4 +/- 1.8 vs. 10.3 +/- 3.4 ng/ml; P less than 0.05). No difference was found in the total GH area response to a nearly equivalent dose of GHRH administered as either multiple pulses or continuous infusion followed by a single GHRH bolus dose. The apparent pulsatile nature of GH secretion during continuous GHRH infusion and the lack of a significant difference in the GH response to a nearly equivalent dose of GHRH administered as either multiple pulses or a continuous infusion suggest that GHRH need not be administered in a pulsatile manner to be an effective therapeutic agent for the stimulation of GH secretion in children with hypothalamic GHRH deficiency. PMID- 3091630 TI - A paraprotein IgA1 occurring in serum, urine, and cerebrospinal fluid (CSF): immunochemical and idiotypic evidence of synthesis in situ by the central nervous system (CNS). AB - A patient affected with multiple myeloma displayed in the serum, urine, and cerebrospinal fluid a paraprotein with identical electrophoretic mobility. The paraprotein, which was polymeric, appeared in the serum and cerebrospinal fluid mainly as the dimer and tetramer, whereas in the urine the tetramer was predominant. The myeloma protein, identified as an IgA1 kappa, was isolated from the serum and urine and submitted to structural analysis. For reasons of scarcity of material, it was decided to approach the structure of the cerebrospinal fluid paraprotein by means of antiidiotypic antiserum. Complete idiotypic identity between, on the one hand, cerebrospinal fluid and, on the other hand, IgA1 isolated from serum and urine and F(ab)2 alpha derived from serum IgA1 was observed. Adsorption experiments confirmed the idiotypic identity among the three biological fluids. Although the blood-brain barrier of the patient was only slightly disturbed, IgA polymers of MW varying from approximately 280,000 to approximately 840,000 appeared in the cerebrospinal fluid. Consequently the results are good evidence for synthesis within the central nervous system by subsequent generations of a malignant B-cell line which invaded the central nervous system. PMID- 3091631 TI - Persisting symptoms after mild head injury: a review of the postconcussive syndrome. AB - Seemingly mild head injuries frequently result in persisting postconcussive syndromes. The etiology of these symptoms is often controversial. Neuropsychological, neurophysiological, and neuropathological evidence that brain damage can occur in the absence of gross neurological deficits after mild injuries is reviewed. Direct impact to the head is not required to cause brain injury. Understandably, psychological factors also play a role in post-head injury disability, but the effect of compensation claims and preinjury psychopathology is often secondary to organic factors. Persons over age 40 or with a history of previous head injury are more vulnerable to protracted symptomatology. PMID- 3091632 TI - Rapid identification of group JK and other corynebacteria with the Minitek system. AB - Forty primary clinical isolates and 50 stock cultures of corynebacteria and coryneform bacteria were tested with the Minitek system (BBL Microbiology Systems, Cockeysville, Md.). The Minitek correctly identified all of these organisms, including JK group isolates, within 12 to 18 h of incubation. The method does not require serum supplements for testing carbohydrate utilization by the bacteria. The Minitek system is an extremely simple and rapid way to identify the JK group, as well as many other corynebacteria, by established identification schemata for these bacteria. PMID- 3091633 TI - Screening method for recovery of methicillin-resistant Staphylococcus aureus from primary plates. AB - A study designed to screen for the presence of methicillin-resistant Staphylococcus aureus from primary plates was conducted from 1 January to 1 September 1985 in a small community hospital. The screening method used a plate of lipovitellin salt mannitol agar and a 4-microgram oxacillin disk incubated at 30 degrees C. Growth of yellow colonies, typical of S. aureus, around the disk without a zone of inhibition was called presumptive methicillin-resistant S. aureus. All susceptibilities were confirmed by using the National Committee for Clinical Laboratory Standards macrodilution technique. Of 224 cultures containing S. aureus, 118 (53%) were positive for methicillin-resistant S. aureus isolates. Of these 118, 111 (94%) were correctly identified from the primary plates as methicillin-resistant S. aureus. Of the 224 isolates, 14 could not be categorized from the primary plates as methicillin-resistant S. aureus due to the small amounts of S. aureus recovered. PMID- 3091634 TI - Disk diffusion susceptibility testing of two macrolide antimicrobial agents: revised interpretive criteria for erythromycin and preliminary guidelines for roxithromycin (RU 965). AB - The 15-micrograms erythromycin disk was twice evaluated for interpretive accuracy against 417 and then 266 strains of gram-positive cocci, Neisseria meningitidis, and Haemophilus influenzae by using the criteria suggested by the National Committee for Clinical Laboratory Standards. These studies suggest a revision of streptococcal and Staphylococcus sp. interpretive guidelines to criteria (greater than or equal to 23 mm = susceptible, less than or equal to 13 mm = resistant) that are more compatible with in vivo erythromycin concentrations. It is also recommended that zone diameters be modified for H. influenzae (greater than or equal to 23 mm = susceptible, less than 22 mm = resistant) and that meningococci not be tested. A wide moderately susceptible category (1.0 to 4.0 micrograms/ml) would primarily include enterococcus strains and those organisms that would then respond only to parenteral administration of erythromycin. Roxithromycin (RU 965 or RU 28965), a new oxime ether erythromycin derivative, was also evaluated by investigator-prepared 15-micrograms disks and later with 30- and 60-micrograms commercial disks. Although roxithromycin was comparable to erythromycin in activity and regression line statistics, changes in the susceptible disk criteria were necessary because of superior roxithromycin serum concentrations and a longer serum half-life. Preliminary susceptible breakpoint criteria were greater than 21 mm = susceptible, 10 to 20 mm = indeterminate, and less than or equal to 9 mm = resistant. By using the recommended interpretive criteria for both macrolides, less than 98% absolute agreement was obtained, therefore suggesting the application of a spectrum class concept. PMID- 3091635 TI - Cost-effective computerization. PMID- 3091636 TI - Basis for defective responses of rheumatoid arthritis synovial fluid lymphocytes to anti-CD3 (T3) antibodies. AB - Synovial fluid mononuclear cells (SFMC) from patients with active rheumatoid arthritis characteristically respond poorly to mitogens. In this study, mitogenic antibodies reactive with the CD3(T3) antigen on human T lymphocytes were used to analyze the basis for the deficiency. OKT3-induced proliferation and release of interleukin 1 (IL-1) and interleukin 2 (IL-2) from SFMC were depressed in all patients. Purified IL-1 or recombinant IL-2 restored proliferative responses in SFMC and increased IL-2 receptor density. Exogenous IL-1 also enhanced IL-2 release. Fractionation of SFMC supernatants on phosphocellulose columns revealed the presence of IL-1 and a potent IL-1 inhibitor. The monocyte-derived IL-1 inhibitor blocked IL-1-dependent responses of normal peripheral blood lymphocytes to OKT3, but had no effect on IL-2-dependent events. These results suggest that IL-1 inhibitor(s) in SFMC impair(s) OKT3-induced mitogenesis by interfering with the effects of IL-1 on T lymphocytes. The net result is deficient IL-2 secretion, IL-2 receptor expression, and impaired cellular proliferation. This novel inhibitory circuit provides a rational explanation for the diminished function of synovial fluid T lymphocytes in rheumatoid arthritis patients. PMID- 3091637 TI - Aberrant immunoglobulin synthesis in light chain amyloidosis. Free light chain and light chain fragment production by human bone marrow cells in short-term tissue culture. AB - Bone marrow cells obtained from 14 patients with light chain amyloid (AL) deposition were examined by biosynthetic labeling techniques. These analyses identified free monoclonal light chain (L-chain) synthesis even in those patients whose serum or urine contained no M protein or free L-chains or only an intact M protein. The experiments also identified a subset of patients whose plasma cells synthesized polypeptides bearing constant region antigenic determinants that migrated more rapidly than intact L-chains on polyacrylamide gels. Since most AL fibrils contain L-chain fragments rather than intact L-chains, these studies suggested that the genesis of the fibril components may reflect aberrant synthesis, proteolytic processing, or both. We also noted that in some individuals the pattern of Ig synthesis normalized after several courses of cytotoxic therapy. Thus, we could use bone marrow Ig synthesis as a sensitive biochemical parameter for monitoring therapy. Finally, the presence of aberrant synthetic products in these clones raised questions about their origin with respect to the normal processes of transcription, translation, and posttranslational modification in Ig-producing cells. PMID- 3091639 TI - Enzyme-linked immunosorbent assay for human urokinase-type plasminogen activator and its proenzyme using a combination of monoclonal and polyclonal antibodies. AB - A sensitive and specific enzyme-linked immunosorbent assay (ELISA) for human urokinase-type plasminogen activator (u-PA) and its inactive proenzyme (pro-u-PA) was developed. A monoclonal antibody was used as solid-phase antibody, while rabbit antibodies against human u-PA followed by peroxidase-conjugated third antibody were used for detection of bound u-PA. No reaction was observed with tissue-type plasminogen activator or with a variety of other human proteins. The assay was used for quantitation of u-PA in human urine and in culture fluid from human tumor cells. The recovery of added pro-u-PA was greater than 95%. A good agreement with the results obtained by enzymatic assays was found. The detection limit was less than 0.1 ng per ml, both for u-PA and pro-u-PA. The advantages of the use of ELISA compared with enzymatic assays and radioimmunoassays for quantitation of u-PA and pro-u-PA in biological samples are discussed. PMID- 3091638 TI - Deficiency of the pyruvate dehydrogenase component in pyruvate dehydrogenase complex-deficient human fibroblasts. Immunological identification. AB - A previously reported deficiency of "total" pyruvate dehydrogenase complex activity is further characterized. Dihydrolipoyl transacetylase (E2) and lipoamide dehydrogenase (E3) activities in the patient's fibroblasts were normal. Pyruvate dehydrogenase activity (E1) was 33% of that in fibroblasts from an age matched control. The amounts of each of the components of pyruvate dehydrogenase complex were analyzed using an immunoblot technique and specific antibodies. Levels of components E2 and E3 were the same in fibroblasts from the patient and control, confirming the activity measurements. However, the levels of E1 alpha and E1 beta were reduced markedly in fibroblasts from the patient. Thus, impairment in the pyruvate dehydrogenase complex activity was due to a reduction in the amount of the E1 component of the complex. PMID- 3091640 TI - The clinical significance of metal binding in convulsion control with sodium valproate. AB - The facility with which certain metal salts of physiological importance can bind to the anticonvulsant drug, sodium valproate, is demonstrated. The products are characterized in vitro and the clinical significance of these findings are discussed in terms of the hair loss side-effect exhibited by some patients who are prescribed the drug for the treatment of epilepsy. The first reports are also given of preliminary in vivo data on the copper and zinc status of paediatric patients on sodium valproate. PMID- 3091641 TI - Uncommon causes of scrotal and inguinal swelling in children: sonographic appearance. AB - Sonography has proven to be a useful diagnostic tool in the evaluation of scrotal abnormalities. Three uncommon, interesting abnormalities--epididymoorchitis as the presenting manifestation of Hemophilus influenzae sepsis, torsion of undescended testis, and abdominoscrotal hydrocele--are presented. All had swelling of both the scrotum and the inguinal area. Sonography played a significant role in the evaluation and management of these patients. PMID- 3091642 TI - Echo-Doppler measurement of splanchnic blood flow in control and cirrhotic subjects. AB - Blood flow in the splanchnic veins was studied in cirrhotics and matched controls by means of a system that combines a mechanical sector scanner with a pulsed Doppler. The measurements were validated in an in vitro model. Echo-doppler studies could be carried out reproducibly in only approximately two-thirds of cases because of poor echo transmission or incomplete cooperation. Portal blood velocity was significantly reduced in cirrhotics (10.5 +/- 0.6 cm/s versus 16.0 +/- 0.5 in controls; p less than 0.001), but portal blood flow was normal because of enlarged portal caliber. A complete hemodynamic evaluation of the splenic and superior mesenteric veins was possible in only a few subjects. In selected patients the technique may prove relevant in the study of hemodynamic effects of drugs and surgery on portal blood flow. PMID- 3091643 TI - Fetal weight estimates in late pregnancy with emphasis on macrosomia. AB - The effectiveness of three methods (Shepard et al, Hadlock et al, and Hansmann) for estimating fetal weight was evaluated in 150 patients at greater than 36 weeks menstrual age. All infants were greater than 2,500 at birth. Only the method of Hadlock et al did not systematically underestimate birth weight. When separate weight subclasses (2,500 to 4,999 g) were examined, the method of Hadlock et al showed better consistency. All models, however, had significant underestimates for the largest subclasses, 4,000 to 4,999 g. The ability to predict the macrosomic infant (greater than or equal to 4,000 g) was only slightly better using the method of Hadlock et al than by the formula of Shephard et al. PMID- 3091644 TI - Indications for routine cranial ultrasound scanning in the nursery. AB - Cranial ultrasonography provides important diagnostic information in neonates. The clinical indications for routine scanning in newborn infants, however, are not established. The purpose of this study is to determine the incidence of cranial pathology detectable by ultrasound in certain clinical states in the neonate. We reviewed the scans and clinical states of 1,031 neonates born between April 1981 and February 1985. We found term infants with dysmorphic features to have the highest incidence of neuropathology (46%), followed by term infants born with macrocephaly (33%), preterm infants (26%), term infants with seizures (26%), and term infants with 1- and 5-min Apgar scores less than 7 (13%). We found a lower incidence (less than 5%) of abnormal CNS findings in the nonasphyxiated term infants with split sutures, cephalohematoma, abnormal neurologic examination, and idiopathic jitteriness. Based on our findings we have concluded that it is important to scan routinely all premature infants, term infants with dysmorphic features, macrocephaly, or seizure disorder, and infants with 1- and 5 min Apgar scores less than 7; routine scanning of term infants with split sutures, cephalohematoma, abnormal neurological examination, or idiopathic jitteriness is not indicated. PMID- 3091645 TI - Sonography of hemorrhagic ovarian cysts. AB - The sonographic appearance of hemorrhagic ovarian cysts (HOC) has received little attention aside from a recent report in adolescent girls. We reviewed the sonographic findings in 14 adults with 15 pathologically proven HOC to see whether there were any consistent sonographic findings that, along with the clinical history, might make possible the diagnosis. The majority (93%) of patients presented with the abrupt onset of lower abdominal or pelvic pain, and each, when clinically appropriate, had a negative serum pregnancy test. Sonographically, all of the masses were cystic except one. The cyst wall was thin and well defined in six cases and thick and irregular in eight. The majority (87%) had internal echoes. These echoes were scattered and low level or diffuse and homogeneous (27%) or complex and echogenic (53%) in nature. Two cysts had numerous septations, and another had a fluid--debris interface. If the pain subsides and the hematocrit remains stable, the premenopausal patient can be managed conservatively. Sonographic follow-up is recommended so that an underlying hemorrhagic ovarian cystic neoplasm can be excluded. This was present in three of our patients, two of whom were postmenopausal. PMID- 3091646 TI - Prenatal diagnosis of cardiovascular malformations in the fetus with situs inversus viscerum during the second trimester of pregnancy. PMID- 3091647 TI - Sonographic diagnosis of a chylous mesenteric cyst. PMID- 3091648 TI - Atypical sonographic findings in splenic infarction. PMID- 3091649 TI - Sonographic diagnosis of cloverleaf skull and thanatophoric dysplasia in the second trimester. PMID- 3091650 TI - Clot formation in the renal artery in the neonate demonstrated by ultrasound. PMID- 3091651 TI - Intrauterine cystocentesis: a simple procedure to relieve anatomic and physiologic dysfunction in the fetus. PMID- 3091652 TI - Hepatic endometrioma. PMID- 3091653 TI - Megacystis-microcolon-intestinal hypoperistalsis syndrome in a male infant. PMID- 3091654 TI - Sonographic features associated with cleft palate. PMID- 3091655 TI - Cape Town, South Africa. PMID- 3091656 TI - Cutaneous manifestations associated with the presence of the lupus anticoagulant. A report of two cases and a review of the literature. AB - Two patients with the lupus anticoagulant exhibited unusual cutaneous manifestations. They both fulfilled four criteria for systemic lupus erythematosus and had experienced deep venous thrombosis. The first patient suffered from a leg ulcer that resembled a pyoderma gangrenosum. The second patient presented erythematous and purplish macules on the fingertips. The histologic studies showed only microthrombosis in the dermal vessels without vasculitis, although such lesions in systemic lupus erythematosus are usually attributed to vasculitis. The association of these cutaneous lesions with lupus anticoagulant has never been reported. It is likely that this association is not fortuitous. After a review of the literature, it seems possible to individualize a new syndrome characterized by the presence of a subgroup of antiphospholipid antibodies. Thrombosis, spontaneous abortions, neurologic manifestations, pulmonary hypertension, positive results of a Coombs' test, and thrombocytopenia can be included in this syndrome, which overlaps with systemic lupus erythematosus. Certain cutaneous symptoms are associated with the presence of lupus anticoagulant or other antiphospholipid antibodies: leg ulcers, distal cutaneous ischemia, widespread cutaneous necrosis, and livedo. They can be considered as the dermatologic manifestations of this syndrome. PMID- 3091657 TI - Some basic facts about models, nursing conceptualizations, and nursing theories. PMID- 3091658 TI - Utilization of child care to increase workshop participation. PMID- 3091659 TI - A competency-based orientation program for psychiatric nursing. PMID- 3091660 TI - Standardizing nurses' continuing education in emergency cardiac care. PMID- 3091661 TI - Effect of independent study units on nursing practice. PMID- 3091662 TI - Outcomes evaluation: continuing education in rheumatology for nurses. PMID- 3091663 TI - Administrative angles. PMID- 3091664 TI - Computer ease. PMID- 3091665 TI - Rumen clearance rates in relation to the occurrence of alfalfa bloat in cattle. 1. Passage of water-soluble markers. AB - Ruminal chlorophyll and rates of passage of two water-soluble markers were simultaneously determined in cattle with different susceptibilities to alfalfa bloat. The markers showed a slower rate of passage from the rumens of more susceptible cattle where the average half-lives for cobalt ethylenediaminetetraacetic acid and chromium-ethylenediaminetetraacetic acid were 12 to 17 h. Average half-life of the markers was 8 h in the rumens of the less susceptible animals. In agreement, chloroplast particles in the liquid phase of rumen contents showed greater accumulation in animals susceptible to bloat, but many more observations were required to detect differences in chlorophyll among animals. This was partly due to the unhomogeneous dispersion of chloroplast fragments in the reticulorumen compared with the uniform distribution of the inert markers. Differences in rumen volumes (estimated from the quantity of marker administered and its initial concentration) were detected among animals, but these did not show a relationship to bloat susceptibility. In vitro studies indicated that alfalfa chloroplast particles were not readily degraded by rumen microorganisms. Our results support earlier conclusions on slower rates of salivation for cattle that bloat compared with those that do not. PMID- 3091666 TI - Galactosyltransferase purified from rat milk is distinct from the human and bovine enzyme. AB - N-Acetylglucosaminide beta 1, 4-galactosyltransferase (EC 2.4.1.22) was purified from rat milk by affinity chromatography on N-acetylglucosamine-Sepharose and alpha-lactalbumin-Sepharose columns. The purified enzyme migrated as three polypeptides of relative molecular weight 59,000, 54,000, and 27,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antiserum raised against the 54K rat protein immunoprecipitated all three polypeptides, suggesting that they share common antigenic sites. The human milk galactosyltransferase, purified under similar conditions, was electrophoretically homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with relative molecular weight 54K, and was not immunoprecipitated by the antiserum to the 54K rat milk protein. In addition, Michaelis constants for the enzyme from rat and human milk differed. The apparent Michaelis constant for N-acetylglucosamine and uridine 5' diphosphate-galactose were 4.8 and .3 mM, respectively, for the rat enzyme, and 1.8 and .028 mM, respectively, for the human enzyme. PMID- 3091667 TI - [Dependence of changes in the redox potential of the medium during the cessation of bacterial growth on the nature of the cell surface and the parameters of the medium]. PMID- 3091668 TI - Neurofibromatosis: relinquishing the masks; a quest for quality of life. AB - Neurofibromatosis (NF) or von Recklinghausen's disease is mankind's most common neurologic genetic disorder, occurring in one of every 3000 live births. While many individuals with NF suffer disfiguring, disabling, or life-threatening complications, NF is extremely variable in its symptoms, intensity, and progression. For many of its victims, NF is a pseudonym for uncertainty and physical and psychosocial havoc. John Merrick, 'The Elephant Man', endured one of the most severe cases of NF ever recorded. Merrick's rejection by post-Dickensian England forced him to become a sideshow circus attraction just to survive. The essence of nursing intervention with NF patients and their families engaged in the quest for quality of life is to restore them to optimal physical and psychosocial functioning, and, ideally, to help them utilize the experience for growth. Many individuals respond to the frustration of NF and society's reactions to the disorder by the wearing of psychological masks. Likewise, nurses may wear emotional masks as a defence against their own discomfort and fears concerning the disorders. Comprehensive nursing management of NF is realized only as nurses and patients relinquish their respective masks. This article examines the nurse's role in genetic disorders with special considerations presented by NF. Adaptation to NF involves coping with NF and its accompanying sequelae and coping with life as it is affected by NF. The concepts of 'chromosomal coping', 'genetophobia', 'genetic guilt, and 'genetic overload syndrome' are presented and analyzed utilizing the theoretical nursing frameworks of Imogene King and Sister Callista Roy. PMID- 3091669 TI - Current thoughts on malabsorption: parenteral, enteral, and oral feeding. PMID- 3091670 TI - Malabsorption in adults: etiology, evaluation, and management. AB - By creating motility disorders, functional pancreatic insufficiency, inadequate bowel absorptive surface, bacterial overgrowth, or mucosal changes, several disease states and treatments have an adverse impact on the body's ability to digest and/or absorb nutrients adequately. The subjective and objective observations associated with the malabsorption syndrome--fatigue, paresthesia, weight change, alterations in bowel movements, and laboratory abnormalities--are caused by losses of macronutrients, electrolytes, minerals, and vitamins in the stool. The absorption workup consists of tests for fat absorption, bowel integrity, pancreatic function, and bacterial overgrowth, which may be performed alone or in combination to aid in identifying specific absorptive defects. Other diagnostic procedures include abdominal x-rays and CAT scans and intestinal biopsy. A logical, well-planned workup is essential in order to avoid unnecessary and/or costly testing. Nutrition management utilizes parenteral, enteral, and oral feeding in combination with adjunct medical measures for maximizing nutrient absorption and minimizing nutrient losses. PMID- 3091671 TI - Cromolyn sodium in ocular allergic diseases. AB - Cromolyn sodium is a highly effective topical anti-allergenic solution for the treatment of vernal, giant papillary, ragweed, and atopic conjunctivitis. It acts by inhibiting the release of histamine and thereby prevents the inflammatory response by subacute type I hypersensitivity reactions. The following paper reviews the drug action of cromolyn sodium and discusses its value in the treatment of type I ocular allergic diseases. PMID- 3091672 TI - Effect of phenobarbital and polychlorinated biphenyls on the toxicity and disposition of 1,2,4,5-tetrachlorobenzene in the rat. AB - Control and phenobarbital (PB) or polychlorinated biphenyl (PCB) pretreated rats were given single oral doses of 14C-1,2,4,5-tetrachlorobenzene (TCB) at 30 or 300 mg/kg b.w. Urine and feces were collected daily for the determination of 14C content. Five animals per group were killed 2 days after dosing and another five animals were killed 7 days later for the determination of hepatic microsomal enzyme activities, histological changes and 14C-content in the major organs and tissues. Pretreatment with PCB or PB did not alter the effects of TCB biochemically or histologically. Both PB and PCB increased the rate of TCB excretion and decreased the levels of radioactivity in most tissues examined at 7 days after dosing. It was concluded that, at the dose ranges studied, pretreatment with PB or PCB did not significantly alter the toxic effects produced by TCB. PMID- 3091673 TI - [Immunology and pregnancy]. PMID- 3091675 TI - Gold-induced ileitis. AB - We describe a patient with rheumatoid arthritis who developed severe ileitis after being treated with gold salts; the patient responded to elimination of the gold therapy and to BAL. PMID- 3091674 TI - The effect of carbon dioxide inhalation on phase characteristics of breathing movements in healthy newborn infants. AB - Chest wall distortion (inward motion of the rib cage on inspiration) has been found recently to reduce the tidal volume during active sleep in the neonatal period. To determine some of the factors that relate to the chest wall distortion and the decreased tidal volume seen in active sleep, a quantification of the phase differences between the movements of the chest wall and those of the abdominal wall, and of the relation of their phase differences to tidal volume was performed on data obtained before and during carbon dioxide stimulation in 15 newborn infants sleeping in the prone position. In quiet sleep, the breathing movements were congruent and regular, and the tidal volume and the mean inspiratory flow increased during carbon dioxide stimulation. In active sleep during exposure to carbon dioxide, the chest wall distortion decreased, the breathing movements were incongruent and the degree of the chest wall distortion was negatively correlated with the tidal volume, while the tidal volume and the mean inspiratory flow was increased. Chest wall distortion did not appear in quiet sleep and was decreased in active sleep in spite of increased ventilation during CO2 stimulation. This study favours the idea that chest wall distortion is caused by a well regulated change in neuromuscular activity and not by the strength of diaphragmatic movements overcoming the mechanical stability of the rib cage. PMID- 3091676 TI - Nasopharyngeal carriage of Neisseria meningitidis in the contacts of index cases of meningococcal meningitis. PMID- 3091677 TI - Fractionation of Fasciola hepatica tegument antigens and their application to the serodiagnosis of experimental fascioliasis by the enzyme-linked immunosorbent assay. AB - A Fasciola hepatica tegument antigen preparation was obtained from intact adult worms by solubilization with a non-ionic detergent, Nonidet P-40. This antigen preparation contains antigens useful for the serodiagnosis of infection with this parasite. However, the antigen preparation is inadequate for use in the enzyme linked immunosorbent assay (ELISA). The present work demonstrates that fractionation by demulsification of this antigen preparation with ammonium sulphate results in a soluble aqueous phase which contains F. hepatica serodiagnostic antigens which can then be applied to the ELISA. This F. hepatica tegument antigen preparation when used in the ELISA can detect rabbit fascioliasis two weeks after infection, with antibody levels peaking by 10 to 12 weeks of infection. PMID- 3091678 TI - The ability of single sex infections of Schistosoma japonicum to induce resistance to reinfection in mice. AB - In four experiments, mice harbouring an average 50, 76 or over 200 Schistosoma japonicum female worms were not resistant when challenged six to eight weeks after infection. The female worms from these single sex infections were stunted and immature (average length 4.6 mm) and induced no overt pathology in the host. Male worm burdens of 60, 135 or 140 also induced little or no resistance to challenge in the host. The males from these single sex infections were fully grown for their age (average length 9 mm) and burdens of 135 or 140 induced distended hepatic portal veins and marked deposition of pigment in the livers of infected mice. PMID- 3091679 TI - The Budd-Chiari syndrome. Possible pathogenetic role of anti-phospholipid antibodies. AB - The case of a young woman with the Budd-Chiari syndrome is reported. She first noticed abdominal symptoms following a late spontaneous abortion. Antiphospholipid antibodies were detected in her serum. We suggest that these may have been causally related to the development of her hepatic disease. PMID- 3091680 TI - 'Lupus' anticoagulant and thrombosis of the hepatic veins (Budd-Chiari syndrome). Report of three patients and review of the literature. AB - Three patients with Budd-Chiari syndrome in association with the 'lupus' anticoagulant are described. This anticoagulant was looked for in our patients with an otherwise idiopathic hepatic venous thrombosis because of the presence of a pronounced thrombocytopenia, a prolonged activated partial thromboplastin time or a history of repeated abortions and deep leg vein thrombosis, respectively. An active search for the 'lupus' anticoagulant should be performed to lower the percentage of apparently idiopathic cases of Budd-Chiari syndrome. PMID- 3091681 TI - Phorbol ester-stimulated T lymphocytes show enhanced adhesion to human endothelial cell monolayers. AB - Phorbol esters have been used to study changes in the adhesiveness of T cells to endothelial cells (EC) after activation. The phorbol esters 12-O-tetra decanoylphorbol-13-acetate (TPA) and 4-beta-phorbol-12,13-dibutyrate (P(Bu)2), but not the biologically inert 4-alpha-phorbol-12,13-didecanoate, strongly increased the binding of 51Cr-labeled T cells to human umbilical vein EC monolayers in microtiter wells. Binding to fibroblasts and gelatin-coated plastic was also increased, but to a lesser extent. Increased binding was observed at 0.3 ng/ml, with maximal enhancement at 33 to 100 ng/ml. Enhancement occurred within 1 min, with maximal increase after 15 min. Preincubation studies with P(Bu)2 showed that binding enhancement was entirely attributable to an effect on T cells, with no action on EC. Additive binding enhancement was seen when phorbol esters and agents that alter adhesion by acting on EC (LPS, IL 1, or IFN-gamma) were used together. The increase in T cell adhesion to EC after T cell activation may contribute to the selective emigration of activated T cells from the blood into developing inflammatory lesions. The rapid increase in binding suggests that this may be an important mechanism for immediate localization of circulating T cells, particularly sensitized T cells, in the cellular immune response, perhaps involving the activation of these cells at the endothelial blood-tissue interface. PMID- 3091682 TI - A role for Lyb-2 in B cell activation mediated by a B cell stimulatory factor. AB - The Lyb-2 system of the mouse is involved in regulation of a proliferative step in the differentiation of B cells responding to T-dependent antigen. The present study concerns the role of Lyb-2 in an early phase of B cell activation with respect to B cell receptor functions for activation factors. It is shown that interaction of monoclonal anti (alpha)-Lyb-2 antibody with Lyb-2 on the B cell surface induces B cell proliferation by synergistic action with B cell growth factor II-containing factor or interleukin 1. In contrast, alpha-Lyb-2 antibody could not synergize with the Con A-induced culture supernatant of T cell hybridoma FS6-14.13 (FS6) containing B cell stimulatory factor-1 (BSF-1; formerly called BCGF I), and the effect of combining the two was only additive on B cell proliferation. Absorption studies showed that BSF-1 in FS6 could be absorbed by unstimulated B cells, about 95% of which were at Go phase of the cell cycle, but not by thymocytes, and more importantly that alpha-Lyb-2 antibody blocked the absorption in an Lyb-2-specific manner, possibly by competing with BSF-1. It is thus likely that alpha-Lyb-2 antibody may interact with a BSF-1 receptor on B cells or a molecule closely associated with it. Interestingly, alpha-Lyb-2 antibody mimicked the action of BSF-1 in a costimulator assay with affinity purified goat alpha-mouse IgM antibody, but could not replace all the activities ascribed to BSF-1. Possible mechanisms involved are discussed. PMID- 3091683 TI - Depletion of donor Ia+ cells before transplantation does not prolong islet allograft survival. AB - Culture of pancreatic islets reduces their immunogenicity and results in prolonged graft survival after allotransplantation. The mechanism by which immunogenicity is reduced by culture is not known, but it has been suggested that prolonged graft survival is the result of the depletion of Ia+ cells from the graft. We studied the effect of eliminating Ia+ cells from islets before allotransplantation. Freshly isolated islets were incubated with anti-Ia serum plus complement or with monoclonal antibody to IAk plus complement or were left untreated before transplantation beneath the renal capsule of diabetic recipients. Incubation with anti-Ia serum plus complement eliminated intra-islet IA+ cells as demonstrated by indirect immunofluorescence staining. Incubation with monoclonal antibody to IAk plus complement significantly reduced but did not eliminate IA+ cells. Neither pretreatment regimen influenced survival of islet allografts placed beneath the renal capsule. However, untreated islets injected into the portal circulation were rejected in a low percentage of cases. We conclude that decreased immunogenicity observed after culture is not due solely to the depletion of Ia+ cells and that the site of engraftment has an important impact on graft survival. PMID- 3091684 TI - High- and low-affinity interleukin 2 receptors: distinctive effects of monoclonal antibodies. AB - We previously established several mouse hybridoma cell lines producing monoclonal antibodies against the human interleukin 2 (IL 2) receptor molecule. As they bind to both high- and low-affinity IL 2 receptors, their effects on binding of 125I labeled IL 2 to high- and low-affinity receptors were examined by Scatchard plot analysis. Two of these monoclonal antibodies, HIEI and H-47, reduced the IL 2 binding affinity of high-affinity receptors from a Kd of 14 to 20 pM to a Kd of 110 to 140 pM, but slightly raised that of low-affinity receptors. These two antibodies scarcely affected the numbers of high- and low-affinity receptors. On the other hand, H-31 completely blocked IL 2 binding to both high- and low affinity receptors, and H-A26 slightly reduced the affinities of both high- and low-affinity receptors, from 17 pM to 28 pM and from 28 nM to 54 nM, respectively. H-48 had little affect on IL 2 binding to high- or low-affinity receptors. By use of these monoclonal antibodies, the inhibitory effect of IL 2 on growth of an HTLV-I-immortalized T cell line was demonstrated to be transmitted from high-affinity, but not low-affinity, receptors. PMID- 3091685 TI - Construction of rat-mouse T cell hybridomas that express regulatable rat interleukin 2 receptor. AB - Spleen cells obtained from Lewis rats were cultured with 4 micrograms/ml Con A for 96 hr, and activated cells were fused with BW5147 mouse T lymphoma cells. Seven clones obtained by fusion expressed rat IL 2R. The expression of rat IL 2R on those hybrid cells could be up-regulated by IL 2 itself, ATL-derived factor, and TPA and CA++ ionophore. Those IL 2R could be down-regulated by murine MoAb ART-18 that detects rat IL 2R. All hybrid clones produced IL 2 constitutively. IL 2 produced by hybrid cells bound to its receptor and promoted the proliferation of hybrid cells in some clones. Incubation of cells with exogenous IL 2 resulted in the proliferation of hybrid cells, whereas the proliferation of some clones was inhibited by exogenous IL 2, indicating that IL 2 had bifunctional properties on cell growth. Rat IL 2R from 6H2-F9 hybrid cells was studied by both one- and two-dimensional SDS-PAGE with ART-18. The IL 2R derived from 6H2-F9 cells had 72,000 to 77,000 and 40,000 to 48,000 m.w. major components under nonreducing conditions, and had 50,000 to 56,000 m.w. major and 35,000 to 38,000 m.w. minor components under reducing conditions. The 110,000 m.w. component, the third component of IL 2R, was constantly observed in 6H2-F9 hybrid cells. PMID- 3091686 TI - Interferon-gamma inhibits the action of B cell stimulatory factor (BSF)-1 on resting B cells. AB - B cell stimulatory factor-1 (BSF-1) stimulates resting B cells to increase in volume and prepares these cells to enter the S phase in response to anti-IgM and other B cell mitogens. Interferon-gamma (IFN-gamma) blocks both the volume enlargement and preparation for DNA synthesis caused by BSF-1, although it has little effect on B cells already stimulated by BSF-1. The capacity of IFN-gamma to inhibit the action of BSF-1 on resting B cells suggests a mutual regulatory interaction between these two T cell-derived products. PMID- 3091688 TI - Induction of meningococcal group B polysaccharide-specific IgG antibodies in mice by using an N-propionylated B polysaccharide-tetanus toxoid conjugate vaccine. AB - Conjugation of the group B meningococcal polysaccharide to tetanus toxoid failed to substantially enhance its immunogenicity in mice. Therefore, additional chemical manipulation of the basic structure of the group B meningococcal polysaccharide was attempted, on the premise that a synthetically derived artificial antigen might be capable of modulating the immune response in mice to produce elevated levels of cross-reactive group B meningococcal polysaccharide specific antibodies. To achieve this, the antigenicity of the modified polysaccharide to group B meningococcal polysaccharide-specific antibodies had to be preserved, and this criterion could only be satisfied in modifications in which the carboxylate and N-carbonyl groups of the sialic acid residues of polysaccharide remained intact. Therefore, the most successful modifications were accomplished by N-deacetylation of the group B meningococcal polysaccharide with strong base to yield a precursor that could then be N-acetylated or N-arylated with different substituents. For example, the introduction of N-propionyl groups, followed by conjugation of the resultant N-propionylated group B meningococcal polysaccharide to tetanus toxoid, yielded an antigen that when injected in mice induced in them high levels of cross-reactive group B meningococcal polysaccharide-specific IgG antibodies. The T cell dependency of this antigen was established when it was demonstrated that the levels of these B polysaccharide specific antibodies could be significantly boosted by using both the N propionylated- and native N-acetylated-group B meningococcal polysaccharide tetanus toxoid conjugates. PMID- 3091687 TI - A monoclonal anti-mouse LFA-1 alpha antibody mimics the biological effects of B cell stimulatory factor-1 (BSF-1). AB - This study describes the generation of a monoclonal mouse x rat antibody (G-48) that recognizes a determinant on the serologically defined LFA-1 alpha-chain. It immunoprecipitates two noncovalently associated polypeptides of 176,000 and 95,000 Mr respectively from lysates of radioiodinated BCL1 cells, T cells, and B cells. G-48 mimics the biological actions of BSF-1 by inducing increased levels of Ia antigen expression on resting B cells, augmenting the proliferation of anti delta-stimulated B cells, and in insolubilized form, inducing IgG1 secretion by LPS-activated B cells. G-48 does not have BCDF mu, BCGF II, nor IL 2 activity. These results demonstrate that LFA-1 plays an important role in B cell activation, proliferation, and differentiation. PMID- 3091689 TI - A region of the immunoglobulin-mu heavy chain necessary for forming pentameric IgM. AB - In order to define the molecular requirements for IgM pentamer formation, we have isolated several mutant hybridomas which produce predominantly monomeric IgM. For one such mutant, 102, we synthesized a cDNA clone of its mu-mRNA, and found an in frame 39-bp deletion, which thus encodes a mu-chain lacking amino acids 550-562, a region spanning the fourth constant domain and the tail of the mu-chain. To prove that this deletion is sufficient to block pentamer formation, we used site directed mutagenesis to construct a mu-gene lacking these 39 bp, and have shown that the expression of this altered mu-gene results in the production of monomeric IgM. PMID- 3091690 TI - Role of DNA synthesis in secretion of immunoglobulin from murine B cells stimulated by T cell derived lymphokines. AB - We have investigated whether cell division is required for induction of Ig secretion from three types of B cells, which represent distinct activation states: normal splenic B cells, anti-Ig-treated B cells, and a monoclonal murine B cell tumor, BCL1. Polyclonal Ig secretion was stimulated in vitro by LPS or by lymphokines produced by EL-4 cells (EL-4 SN), which includes B cell growth factor II (BCGF II). LPS and EL-4 SN were mitogenic for all three cell populations and stimulated substantial IgM secretion from both B cells and anti-Ig blasts. Aphidicolin, a reversible inhibitor of DNA synthesis, abolished IgM secretion from B cells and anti-Ig blasts induced by either mitogen, indicating that Ig secreting cells in these cultures are part of a cycling population. BCL1 tumor cells respond to BCGF II (but not to interleukin 2 or B cell stimulatory factor 1) with IgM secretion and cell division, allowing a direct assessment of the influence of BCGF II-stimulated cell division on secretion of IgM. Secretion by these cells during the first 24 hr of culture was not substantially affected by aphidicolin, but secretion at 48 or 72 hr was markedly inhibited. Culture of BCL1 cells for 48 hr with aphidicolin alone had no effect on cell viability or on subsequent responsiveness if the drug was removed, eliminating non-specific toxicity as an explanation of the drug's effect. Addition of aphidicolin during the last 24 hr of culture to either normal B cells or BCL1 cells was much less effective at inhibiting IgM secretion. These results indicate that the cells that secrete IgM in response to BCGF II also synthesize DNA when exposed to this factor. Thus, induction of high-rate Ig secretion from murine B cells by some stimuli, including BCGF II, may require at least one round of cell division. PMID- 3091691 TI - Monoclonal antibodies to the CD5 antigen can provide the necessary second signal for activation of isolated resting T cells by solid-phase-bound OKT3. AB - Activation of human peripheral blood T cells by the anti-CD3 antibody OKT3 has been shown to require not only cross-linking of CD3 molecules with multimeric binding of the Fc part of OKT3 to a solid support, but also a second accessory cell-provided signal. Accordingly, measurement of T cell activation in cultures of highly enriched T cells with solid-phase-bound OKT3 can be used to investigate whether other agents can replace accessory cells. In this study we examined the capacity of anti-CD5 monoclonal antibodies to provide the additional activation signal. Resting T cells were prepared by isolating E rosette-positive cells, by removing OKM1(+) and HLA-DR(+) cells by panning, and by subsequent treatment of the cells with L-leucine methyl ester to kill remaining monocytes. These T cells were unresponsive to phytohemagglutinin (PHA) or to solid-phase-bound OKT3. However, when cultured in the presence of an anti-CD5 monoclonal antibody (anti Leu-1, OKT1, or anti-T1), a proliferative response to solid-phase-bound OKT3 (but not to soluble OKT3 or to PHA) was observed. Anti-CD5 had no functional effect by itself, but in association with solid-phase-bound OKT3 it enhanced IL 2 receptor expression and IL 2 production and it initiated T cell proliferation. T cell proliferation under these conditions could be inhibited by an IL 2 receptor blocking antibody anti-Tac, thus confirming that anti-CD5 provides the second signal for an IL 2-dependent pathway of T cell proliferation. Preincubation of T cells with anti-Leu-1 or OKT1 resulted in complete loss of CD5 antigenicity, and such CD5 modulation was sufficient to induce a proliferative response to solid phase-bound OKT3. It is concluded that in T cell activation by solid-phase-bound OKT3 the necessary additional signal can be provided by modulation of the CD5 antigen with an anti-CD5 antibody. CD5 therefore appears to be a positive signal receptor on the T cell membrane, whose physiologic ligand still has to be determined. PMID- 3091693 TI - Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. AB - We have used the quantitative binding of murine monoclonal antibodies to the surface of cultured human umbilical vein endothelial (HUVE) cells to study the responses of HUVE cells to three different immune mediators: interleukin 1 (IL 1), tumor necrosis factor (TNF), and immune interferon (IFN-gamma). Antibody H4/18, reactive with an endothelial cell-specific activation antigen, does not bind to unstimulated HUVE cells but shows rapidly and transiently inducible binding (peak 4 to 6 hr) to cells stimulated by IL 1 or TNF that declines to basal levels by 24 hr, even in the continued presence of mediator. Binding of H4/18 is unaffected by IFN-gamma. Antibody RR1/1, reactive with intercellular adhesion molecule 1, binds to unstimulated HUVE cells, but binding is rapidly increased (plateau 24 hr) after stimulation by IL 1 or TNF and slowly increased (over several days) by IFN-gamma. In contrast to H4/18 binding, the increase in RR1/1 binding is sustained in the continued presence of mediator. Antibody W6/32, reactive with HLA-A,B antigens, binds to unstimulated HUVE cells and shows gradually progressive increases (over several days) in binding upon treatment with IFN-gamma or TNF. These observations demonstrate that HUVE cells show distinct but overlapping patterns of antigenic modulation in response to three different lymphokines, and suggest that the "activation" of endothelial cells observed in situ may represent a complex integration of several lymphokine mediated signals. PMID- 3091692 TI - Amelioration of acute graft vs host disease due to minor histocompatibility antigens by in vivo administration of anti-interleukin 2 receptor antibody. AB - Lethal acute graft vs host disease (GVHD) elicited by minor histocompatibility antigens was studied in a murine model of bone marrow transplantation (B10.BR--- CBA). The severity of GVHD was reduced by both clinical and histologic parameters when transplant recipients received injections of a monoclonal antibody directed against the interleukin 2 receptor. This study suggests that anti-interleukin 2 receptor antibodies may be useful in clinical marrow transplantation and provides additional evidence that monoclonal antibodies that block T cell function in vitro may be of therapeutic value in vivo. PMID- 3091694 TI - Contribution of macrophages to immediate hypersensitivity reaction. AB - The interaction of mast cells with other leukocytes during immediate hypersensitivity reactions was tested by in vivo and in vitro experiments. Intraperitoneal challenge of passively sensitized rats with antigen caused the production of peptidoleukotrienes, leukotriene (LT)B4, thromboxane (TX)B2, and 6 keto-prostaglandin (PG) F1 alpha in the peritoneal cavity. Pretreatment of the rats with thioglycollate i.p. markedly changed the amount of eicosanoids formed. When polymorphonuclear leukocytes were the predominant cell type in the peritoneal exudate, both LTC4 and 6-keto-PGF1 alpha were decreased by 75% each and TXB2 by 50%. When elicited macrophages were predominant, there was an additional reduction in LTC4 by 68% as compared with 18 hr after thioglycollate treatment, but no additional change in the other arachidonic acid metabolites. In vitro antigen challenge of passively sensitized mouse bone marrow-derived mast cells caused the release of LTC4, LTB4, 6-trans-LTB4, 5-hydroxyeicosatetraenoic (5-HETE), and TXB2. Exposure to antigen of these mast cells in the presence of resident peritoneal macrophages markedly altered eicosanoid formation. Early in the time course (2 to 15 min), macrophages markedly enhanced all 5-lipoxygenase products. However, later in the time course (30 to 120 min), these products were decreased. This decrease was reversed by catalase and superoxide dismutase, which suggests the involvement of oxygen radicals. These active oxygen species also seemed to be generated by mast cells, because these enzymes caused an increase in 5-lipoxygenase products when mast cells were challenged alone. RIA of cyclooxygenase products showed that mast cells released only TXB2 when stimulated with antigen. When they were stimulated in the presence of macrophages, TXB2 and also PGE2 and 6-keto-PGF1 alpha were synthesized. Therefore, macrophages probably contribute the PGE2 and 6-keto-PGF1 alpha. Because the same amount of TXB2 was generated whether macrophages were present or not, the mast cells seem to be the major source of this compound. These data indicate that macrophages and possibly polymorphonuclear leukocytes participate in immediate hypersensitivity reactions. PMID- 3091695 TI - Identification of a genetic locus, Rsm-1, controlling protective immunity against Schistosoma mansoni. AB - Mice of most inbred strains develop moderate to high levels of resistance to challenge infection on vaccination with radiation-attenuated cercariae of Schistosoma mansoni. P strain mice, however, fail to display significant protective immunity after exposure to the same vaccine. To examine the genetic basis of this polymorphism in host immunity, vaccine-induced resistance was examined in (C57/BL6J X P/N)F1, F2, and reciprocal backcross generations. The defective immunity which characterizes the P strain parent was found to be inherited in a fully recessive manner and to be controlled by a single genetic locus, which we have designated Rsm-1. Linkage analyses revealed that Rsm-1 is not genetically associated with the major histocompatibility complex (chromosome 17), the immunoglobulin heavy chain locus (chromosome 12), or a single locus influencing defective anti-schistosomulum IgM antibody responses in the P parental stock. These data provide the first example of single gene control of vaccine-induced immunity against a helminth infection. Because P mice are also defective in their capacity to develop tumoricidal macrophages and in their immunity to Leishmania major, genes encoded by the Rsm-1 locus may play a general role in resistance to infection and malignancy. PMID- 3091696 TI - Chemotactic response of splenic mononuclear cells to angiotensin II in murine schistosomiasis. AB - Murine Schistosomiasis mansoni is a parasitic infection associated with a delayed type hypersensitivity granulomatous reaction to the schistosome eggs. This reaction is characterized by the accumulation of mononuclear cells and other inflammatory cell types around the eggs. Granuloma macrophages produce angiotensin II (AII), which appears to have immunoregulatory function. By using an in vitro chemotaxis assay, this study demonstrated that AII is a chemotactic factor for splenic mononuclear cells derived from infected mice. The response was bimodal, with peak activities occurring at 10(-10) and 10(-6) M. AII was chemotactic for T lymphocytes, B lymphocytes, and a large population of unidentified mononuclear cells at the optimal chemotactic concentrations of the peptide. At high concentrations, AII was also chemotactic for phagocytic mononuclear cells. Sar1, ala8-AII, an analog of AII with antagonist activity, completely blocked AII-induced chemotaxis. A [3H]-AII binding assay revealed high affinity specific binding on spleen cells. The binding was rapid, was dependent on radioligand concentration, and was reversible. These latter observations suggest that the chemotactic activity of AII for subpopulations of splenic mononuclear cells is mediated via AII receptors. PMID- 3091697 TI - Enzyme-linked immunosorbent assay of mouse interleukin-2 receptors. AB - An enzyme-linked immunosorbent assay (ELISA) which measures soluble mouse interleukin-2 receptor (IL-2R) was developed, using two monoclonal anti-mouse IL 2R antibodies directed against two different epitopes of the IL-2R molecule. The ELISA-reactive material was identical with the IL-2R material which was capable of binding to affinity support beads coupled with recombinant interleukin-2 (IL 2). Quantitation of IL-2R in detergent-lysed cells was compared to that of the purified IL-2R, and the detection limit was estimated to be within the range of 2 10 ng/ml of a test sample. This sensitivity made it possible to determine soluble IL-2R levels in cell culture supernatants and mouse sera. PMID- 3091698 TI - Determination of human T cell activity in response to allogeneic cells and mitogens. An immunochemical assay for gamma-interferon is more sensitive and specific than a proliferation assay. AB - T lymphocytes proliferate and secrete lymphokines in response to allogeneic cells, mitogens and other stimuli. Cell proliferation as measured by [3H]thymidine ([3H]Tdr) incorporation into DNA has been routinely used to determine T cell responses in research and clinical laboratories. We have compared the sensitivity of an immunoradiometric assay (IRMA) for human gamma interferon (IFN-gamma) (Chang et al., 1984), with that of the conventional [3H]Tdr incorporation assay in the measurement of T cell responses to antigens and mitogens in culture. Peripheral blood mononuclear cells (PBMs) were incubated in the presence and absence of phytohemagglutinin (PHA) or mononuclear cells from another individual for various periods of time. The culture fluids were collected for determining IFN-gamma and the cells were assayed for [3H]Tdr incorporation. Results of measurements were expressed in terms of stimulation indices. Both IFN gamma secretion and thymidine incorporation were measurable in mixed lymphocyte cultures after incubation for 3 days, and in PHA stimulated culture after 24 h of incubation. The stimulation indices reflecting increased gamma-interferon were found to be more pronounced and more consistent than those of [3H]Tdr incorporation. PMID- 3091699 TI - Ossification of stylohyoid ligament with pseudojoint formation--a case report. PMID- 3091700 TI - Interplay of immunoglobulin G heavy chain markers (Gm) and HLA in predisposing to systemic lupus nephritis. AB - We have studied the distribution of IgG heavy chain markers (Gm) among 90 Hungarian patients with systemic lupus erythematosus (SLE) (55 of whom were also typed for HLA). This study confirms previously described increases in HLA-B8 and DR3 in this condition. No difference in the distribution of Gm phenotypes was found between patients and 168 controls from the same geographical area. HLA B8/Gm homozygous individuals were, however, at greater risk for SLE (relative risk = 5.13) compared to B8 + Gm heterozygotes or B8- individuals, irrespective of Gm phenotype. When patients with renal manifestation (n = 40) were compared to those without, the Gm phenotype 3; 5, 13 was found to be significantly increased (chi 2 = 10.36, P less than 0.0001, relative risk (RR) = 4.69). HLA and Gm increased additively the risk for renal manifestations in that for those patients who were both Gm3;5,13+ and HLA-B8+, PR was 110, while it was 21.2 for Gm3;5, 13 /B8+, 7.9 for Gm3;5, 13+/B8- and 1.0 for Gm3;5, 13-/B8- patients. The study suggests that combined HLA and Gm typing can be used to identify SLE patients at high risk for manifesting renal abnormalities. PMID- 3091701 TI - Preferential expression of catfish light chain immunoglobulin isotypes in anti dinitrophenyl antibodies. AB - Previous studies indicated that immunoglobulins of the channel catfish, Ictalurus punctatus, contained two distinct isotypes of light chains. These different light chains, designated F and G, are reminiscent of kappa and lambda light chains of higher animals. This study was undertaken to establish whether or not there was preferential expression of one of the light chains in antibodies induced to the dinitrophenyl moiety during the course of the catfish humoral antibody response. The results indicated that, although antibody produced very early (1-2 weeks) after primary immunization contained significant amounts (approximately 20%) of G light chains, the vast majority (approximately 90%) of antibody produced later (3 weeks through 1 year) was of the F isotype. Thus fish, as well as higher vertebrates, can express different isotypes of antibody during the immune response. PMID- 3091702 TI - Effect of ischemia and reperfusion of pig skin flaps on epidermal glycogen metabolism. AB - Pedicled skin flaps in the pig have been used to investigate the effects of 3-h ischemia and reperfusion on the epidermal metabolism of glycogen and glucose. Epidermal glycogen content fell steadily at a rate of about 1.2 mumol of glucose equivalents per g wet weight per h whereas the rate of glucose consumption declined from 1.8 mumol per g wet weight during the first hour to about 0.25 mumol per g wet weight in the third hour. During ischemia the proportion of glycogen synthase in the I form increased progressively from an initial value of about 8% to about 70%, but the proportion of phosphorylase in the a form decreased only in the third hour of ischemia. The concentration of ATP decreased and ADP and AMP increased but the total pool of epidermal adenine nucleotides was not depleted. On reperfusion, these changes were reversed and normal epidermal concentrations of glucose and adenine nucleotides were restored within 30 min and remained stable thereafter. The resynthesis of glycogen proceeded at a steady rate of about 1 mumol per h per g wet weight and the phosphorylation state of both glycogen synthase and phosphorylase approached normal values after 3 h. It is concluded that epidermal glycogenolysis in ischemia is, at least in part, a consequence of activation of phosphorylase b by AMP, and that glycogen resynthesis on reperfusion is promoted by the ischemic activation of glycogen synthase. PMID- 3091703 TI - Leu-3/T4 expression on epidermal Langerhans cells in normal and diseased skin. AB - Recent evidence exists that the expression of the Leu-3/T4 antigen is not restricted to thymus-derived lymphocytes but can also be detected on mononuclear phagocytes and epidermal Langerhans cells (LC). When searching for the presence of Leu-3/T4 antigen-bearing cells in tissue sections of a variety of inflammatory and neoplastic skin disorders, we observed quantitative and qualitative differences in the intensity of anti-Leu-3a labeling of epidermal dendritic cells. Reasoning that Leu-3/T4 expression by these cells might be a dynamic event, we compared the anti-Leu-3a LC staining pattern in clinically normal appearing skin (CNAS) with the expression of this antigen on epidermal dendritic cells in a variety of skin disorders. For this purpose, 4-microns cryostat sections were exposed to the monoclonal anti-Leu-3a reagent and antibody binding was visualized by a sensitive 4-step immunoperoxidase technique. Within CNAS, Leu 3a+ dendritic epidermal cells were visualized at the threshold of detectability. Immunoelectron microscopic studies confirmed the LC nature of these cells. In sharp contrast to CNAS, strong and prominent anti-Leu-3a LC labeling was almost invariably encountered in biopsy specimens from patients with cutaneous T-cell lymphoma and various inflammatory conditions but not in proliferative disorders of resident skin cells. Whereas in CNAS the density of T6+ epidermal dendritic cells greatly exceeded that of anti-Leu-3a-reactive dendritic cells, these differences were less pronounced in diseased skin. Our results: confirm earlier observations that epidermal LC may bear Leu-3/T4 antigens; and in addition, suggest that the degree of Leu-3/T4 expression is regulated by signals from inflammatory cells. The induction of class II alloantigen receptors on class II alloantigen-bearing LC may represent an important regulation mechanism of antigen presenting cell function. PMID- 3091704 TI - Delayed-amelanotic (DAM or Smyth) chicken: melanocyte dysfunction in vivo and in vitro. AB - Chickens of the autoimmune delayed-amelanotic (DAM or Smyth) line develop postnatal feather amelanosis and severe visual defects, both of which are presumed to be due to a dysfunction of melanocytes and a subsequent autoimmune response that eliminates pigment cells. In this report we elucidate further the melanocytic defect. We present a morphologic analysis of the mildly affected erratic (eDAM) group of Smyth chicken whose partial depigmentation and lack of visual impairment resemble human vitiligo more so than do the complete amelanosis and blindness in the classical Smyth line. Histologically, the sequential events leading to amelanosis in the young Smyth chicken occur simultaneously in the feathers of adult eDAM Smyth chickens, and the infiltration of the feather pulp with mononuclear leukocytes correlates with the extent of local pigmentary abnormality. Cytochemical localizations of dopa-oxidase and acid-phosphatase activities in eDAM feather melanocytes suggest that melanogenesis and autophagocytosis of melanosomes occur in tandem and that the rates of both are higher in these cells than in melanocytes of normally pigmented control chickens. Assays for tyrosinase activity in feather follicles indicate a hypermelanization in eDAM feathers and in the pigmented feathers of young Smyth chicks prior to the onset of depigmentation. Finally, we report on the establishment of pure, proliferative cultures of neural crest-derived melanocytes from control and Smyth chicken embryos. The degenerative events in Smyth chicken melanocyte cultures mimic in part those of the cells in vivo and are therefore indicative of a genetic defect that is independent of the immune system. PMID- 3091705 TI - A model for quantifying absorption through abnormal skin. AB - Techniques are available for quantitatively studying factors governing absorption through normal skin (in vivo and in vitro) but relatively little is known about the permeability of abnormal skin. We have designed and evaluated an in vivo model for quantifying absorption through abnormal skin. Absorption of [3H]mannitol and [14C]octyl benzoate was studied through altered rat skin. [3H]Mannitol penetrated normal skin much more slowly than did [14C]octyl benzoate. Abnormal skin was more permeable to [3H]mannitol and [14C]octyl benzoate, absorption was greater than 100X and greater than 2X greater, respectively, than normal. The in vivo model has been successfully used to quantify absorption through abnormal skin. PMID- 3091706 TI - Carcinogenesis studies with benzoyl peroxide (Panoxyl gel 5%). AB - Several groups of hairless mice were given UV radiation with and without pretreatment with 7,12-dimethylbenz(a)anthracene (DMBA), 5% benzoyl peroxide in a gel (Panoxyl), and gel alone, in various combinations, with appropriate control groups included, in order to see whether benzoyl peroxide, which is known to enhance chemical skin carcinogenesis after a single, small dose of DMBA, also enhances UV carcinogenesis. The mice were observed for skin tumors, and all skin lesions were histologically investigated. The percentage of tumor-bearing animals with time is called the tumor rate, the total number of tumors occurring is called the tumor yield. Continual treatment with 5% benzoyl peroxide in gel twice a week, with or without a short pretreatment period of UV radiation resulted in only 2 skin carcinomas, which is remarkable, but not significant. Both Panoxyl and gel alone enhanced tumorigenicity significantly in animals pretreated with a single dose of 51.2 micrograms DMBA. There was no difference between the enhancement caused by Panoxyl and the gel as regards the tumor rate, but when measured as final tumor yield, Panoxyl was slightly more tumor-enhancing than gel alone. However, both Panoxyl and gel protected significantly against UV tumorigenesis (all tumors). There was no difference between the protective effect of the 2 types of treatment. Neither Panoxyl nor gel alone influenced significantly UV skin carcinogenesis (malignant tumors). It is concluded that under these experimental conditions both Panoxyl and gel alone tend to protect against the tumorigenicity and do not enhance the carcinogenicity of UV radiation in hairless mice, whereas both gel and Panoxyl enhance chemical carcinogenesis. The carcinogenic mechanisms may be different for UV and chemical carcinogenesis, respectively. PMID- 3091707 TI - Specific inhibition by antityrosinase antibodies of tyrosinase-mediated melanogenesis. AB - Polyclonal antibodies to hamster melanoma tyrosinase were raised in rabbits, and series of immunoinhibition experiments with a purified enzyme and specific immunoglobulins were carried out. Tyrosinase activity was determined by a set of radiochemical and spectrophotometric methods utilizing tyrosine, dopa, dopamine, or dihydroxyindole (DHI) as substrates. The quantitative data obtained indicated that the complexing of tyrosinase with its specific antibody inhibited melanogenesis in a specific manner: dopachrome formation from dopa and dopamine conversion to melanin were not affected and all other enzyme activities comprising the DHI oxidation step were inhibited to various degrees. Additionally, tyrosine hydroxylation was also slightly inhibited. The data obtained implied that melanogenesis was restricted at the point of DHI oxidation. From observations on the immunoinhibition of a DHI oxidation at varying dopa cofactor concentrations, we propose that dopa-cofactor may be bound at separate site than DHI and thus may act as a positive allosteric effector for DHI oxidation by tyrosinase. Study of tyrosinase immunoinhibition by the antibodies against the enzyme thus seems to provide a valuable system for investigating the tyrosinase-mediated melanogenesis. PMID- 3091708 TI - Pseudomonas aeruginosa polysaccharide-tetanus toxoid conjugate vaccine: safety and immunogenicity in humans. AB - A Pseudomonas aeruginosa polysaccharide-tetanus toxoid (Ttxd) conjugate vaccine was produced. Polysaccharide was derived from lipopolysaccharide (LPS) and covalently linked to Ttxd by using carbodiimide with adipic acid dihydrazide as a spacer molecule. The conjugate possessed a relative molecular weight of greater than 350,000 and was nontoxic and nonpyrogenic. The vaccine bound serospecific monoclonal antibodies with an avidity similar to LPS and reacted with murine and human opsonic antibody. The vaccine was immunogenic in rabbits and mice and elicited IgG antibody to both LPS and Ttxd. The vaccine was safe when parenterally administered to humans and evoked only mild, transient reactions. Mean titers of IgG antibody to LPS rose 19-fold after immunization, with 82% of the volunteers responding with a fourfold or greater rise in titer. IgG antibody to LPS evoked after immunization was opsonic and highly effective at preventing fatal experimental burn wound sepsis due to P. aeruginosa. PMID- 3091709 TI - Radioimmunoprecipitation of [35S]methionine-radiolabeled proteins of Rickettsia conorii and Rickettsia rickettsii. PMID- 3091710 TI - Antimicrobial activity of human milk against pediatric pathogens. PMID- 3091711 TI - T-cell replacing factor activity of recombinant-derived interleukin-2 requires gamma-interferon. AB - In this study we show that recombinant-derived human interleukin-2 (rIL-2) has potent T-cell replacing activity in antigen-driven murine antibody responses of T depleted spleen cells. This T-cell replacing factor (TRF) effect of rIL-2 is antigen specific. By the use of a variety of antibodies to gamma-interferon (IFN gamma), including antibody from an interspecies hybridoma, we demonstrate that this TRF activity depends upon the production of IFN-gamma in the responding cell cultures, i.e., antibody to IFN-gamma blocks TRF activity. In addition, we show that the cell-to-cell allogeneic helper effect of T cells for antibody responses is similarly inhibited by antibodies to IFN-gamma. The inhibition of response produced by the antibodies is reversed by the addition of excess rIFN-gamma to the cultures. The results demonstrate that IFN-gamma is a necessary intermediate mediator for TRF activity mediated by IL-2 and also by T-cell-mediated help for B cells. Thus, even recombinant-derived lymphokines have complex secondary levels of action on responding cells. Antibodies to individual lymphokines are clearly a powerful resource to analyze the role of soluble factors in cellular responses. PMID- 3091712 TI - Interferon-mediated induction of class I MHC products in human neuronal cell lines: analysis of HLA and beta 2-m RNA, and HLA-A and HLA-B proteins and polymorphic specificities. AB - Gamma-interferon (IFN-gamma) increases class I major histocompatibility complex (MHC) expression in human neuroblastoma cell lines. These cells are of interest because of the initial paucity of MHC expression, a paucity that is also seen in neural tumors and normal brain. The aim of this study was to define further the class I molecules, and to begin to analyze the genetic basis of the regulation. Northern blot analysis with cDNA probes for HLA and beta 2-microglobulin (beta 2 m) RNAs shows that both are present in reduced quantities (relative to a B-cell control) in control neuroblastoma cells. The levels of both RNAs are increased following IFN-gamma. This behavior parallels that of the corresponding polypeptides. Further monoclonal antibody analysis of the class I proteins from IFN-treated cells shows that both HLA-A and HLA-B are present. For two cell lines, expression of appropriate polymorphic specificities is also shown to be increased. We conclude that IFN-gamma can cause increased expression of appropriate HLA-A,B,C specificities on cells of neuronal origin. This raises the question of whether these molecules can serve predicted immunological functions. PMID- 3091713 TI - A sensitive radioimmunoprecipitation assay for the detection of antibody to recombinant human gamma-interferon: comparison to a bioassay neutralization test. AB - This report describes a specific radioimmunoprecipitation (RIP) assay for the detection of antibodies to recombinant DNA (rDNA) derived human gamma-interferon (rHuIFN-gamma). The assay was shown not to detect antibodies to rHuIFN-alpha, rHuIFN-beta, human lymphotoxin, or E. coli proteins and was reproducible with intraassay and interassay coefficients of variation of 1.6 and 3%, respectively, for the log titer of a high positive control. Comparison of this assay with a standard bioassay for detection of neutralizing antibody (abrogation of the inhibitory effect of rHuIFN-gamma on EMC virus replication in A549 cells) demonstrated that the RIP assay was more sensitive for detection of HuIFN-gamma neutralizing monoclonal antibody. Nonneutralizing monoclonal antibody was detectable in the RIP assay but not in the bioassay neutralization test. Examination of polyclonal antisera (rabbit and monkey) that contained neutralizing antibodies also demonstrated the RIP system to be a more sensitive indicator of the presence of antibodies than the bioassay neutralization test. In preliminary studies of human samples (86 patients) from clinical trials using an assay precipitation system capable of detecting antibody of the IgG, IgM, IgA, and IgE classes, no antibody to rHuIFN-gamma was observed. These patients were also found negative for neutralizing antibody to rHuIFN-gamma. PMID- 3091714 TI - Neurological damage after sagittal split osteotomy. AB - Neurological damage following the sagittal split osteotomy is a commonly recognised complication. The results of 38 osteotomies in 19 patients following a minimum post-operative period of 2 years is presented. Subjective evaluation demonstrated normal sensation in 73.7% of osteotomy sides. However, objective evaluation demonstrated normal sensation in only 34.2% of sides. The remainder had a variable degree of sensory loss. PMID- 3091715 TI - Incidence and aetiological pattern of jaw fractures in Greenland. AB - All of the cases involving fractures of the mandible and/or maxilla in Greenland were recorded in a 1 1/2 year period beginning 1 July 1981. Further information of aetiological patterns was added from 2 studies of mandibular fractures in Godthab/Greenland. The incidence of jaw fractures in Greenland (17 to 10,000 per year) was the highest ever reported. In 90% of these cases, the cause of fractures were interpersonal violence. Jaw fractures were encountered in nearly all districts of Greenland, most often in urban areas and the patients were chiefly of Greenlandic descent. The % of patients in the age group of 20-29 years was extremely high (57%) as was the women (36%). 75% of the women were ill treated by their spouses. In half of the cases, the victims and the assailants were related. Victims unknown to the assailants made up only 20% of the cases. These were trends typical of a small society. Compared to other reports, violence in Greenland was aggravated and involvement of alcohol was seen in 4 out of 5 cases. Regulation and deregulation of alcohol in Greenland had only temporary effects on the occurrence of jaw fractures. Aetiological patterns of jaw fractures changes from one subculture to another depending on social conditions. The figures from Greenland demonstrated this. PMID- 3091716 TI - Protracted dislocation of the temporomandibular joint. AB - A review of the literature concerning 37 cases of long-standing dislocation of the temporomandibular joint is presented. 3 new cases are added. A wide variety of methods of treatment has been used in the past. A survey of these methods will be given and a scheme of recommendation for managing the different clinical situations will be discussed. PMID- 3091717 TI - A double-blind, randomized study of naproxen and acetylsalicylic acid after surgical removal of impacted lower third molars. AB - 100 patients had an impacted lower 3rd molar surgically removed in a double-blind study. Naproxen (500 mg b.i.d.) or acetylsalicylic acid (ASA) (1 g t.i.d.) were administered to the patients. Paracetamol was allowed as escape medication. 49 patients received naproxen and 51 ASA. 4 patients from each group were excluded because they took other analgesics, took too few tablets, were lost to follow-up or had misunderstood the instructions. There was a significantly better over all analgesic effect of naproxen than ASA (p = 0.004). More patients in the naproxen group than in the ASA group (p less than 0.01) would accept treatment with the same drug again. 4 patients, all from the ASA group, complained spontaneously about side effects. PMID- 3091718 TI - A double-blind crossover trial of CMC- and mucin-containing saliva substitutes. AB - The aim of this investigation was to describe and to compare the effectiveness of a CMC- and a mucin-containing saliva substitute. 22 post-radiation patients, 17 Sjogren's Syndrome patients and 3 patients with xerostomia of unknown origin used a CMC- and a mucin-containing saliva substitute, each for 1 week in an arbitrary sequence. Neither the patient, the assistant, nor the physician were aware of the substitute being used. Each patient had to complete a questionnaire at 3 different intervals during the trial. One of the conclusions of this study is that mucin-containing substitutes are preferred by patients when compared to CMC containing substitutes. PMID- 3091719 TI - Late effects of radiation treatment of tongue and floor-of-mouth cancer on the dentition, saliva secretion, mucous membranes and the lower jaw. AB - The purpose of this study was to determine retrospectively any changes in the dentition, saliva secretion, mucous membranes and the lower jaw resulting from the radiation treatment given to patients with cancer of the tongue or floor of the mouth. The study covers 29 patients treated at the Department of Radiotherapy and Oncology of Helsinki University Central Hospital between 1972 and 1981. 23 of the patients were treated for cancer of the tongue and the remaining 6 for cancer of the floor of the mouth. The radiation doses ranged from 5300 to 6700 rad. Clinical examination revealed that the number of carious teeth doubled as a result of radiotherapy, while the incidence of cervical lesions increased by a factor of 10, both compared with the controls. About 70% of the patients studied were found to have either moderate or extensive fungal growth. Stimulated saliva secretion had fallen to about 20% and resting saliva secretion to about 30% of the values for the control group. Radiography revealed pathological changes in the mandible in 34% of the patients. Clinically, 2 patients were found to have extra-oral fistulae. In 1 of these, the spontaneously fractured end of the mandible was visible for several cms. 3 of the patients had undergone hemimandibulectomy because of osteoradionecrosis. PMID- 3091720 TI - Temporomandibular joint arthroscopy by inferolateral approach. AB - A clinically successful technique for temporomandibular joint (TMJ) arthroscopy by the inferolateral approach is reported. The outline of the superior and inferior articular cavities of the TMJ except for the lower anterior pouch could be visualised; arthroscopy could be performed on most patients under local anesthesia in the out-patient operating room. Clinical usefulness and security of the TMJ arthroscopy based upon anatomical understanding is described. PMID- 3091721 TI - Universal polycarbonate fracture splint and its direct bonding potential. AB - A polycarbonate splint has been presented which offers the advantage of the ability of being bonded and/or wired into place. This new type of splint offers several advantages over traditional steel splints. The splint can be bonded and/or wired to the dental arch; the bonding method can be a time-saver. The polycarbonate material is readily malleable and does not possess an intrinsic tension or spring usually found in plastics when they are bent or shaped. The splint is highly esthetic when compared to steel splints. Polycarbonate splints are more economical than steel splints. Molded plastic surfaces are smoother and are more compatible with the oral mucosal than the stamped steel surfaces. Finally, and most importantly, the patient acceptance of polycarbonate splints appears to be very good in comparison with steel splints. The above advantages seem to indicate that the future acceptance of this type of splint for maxillofacial injuries will be good, although, it should be understood that plastic splints are not as strong as steel splints and may occasionally break after several weeks of use. Breakage, however, may not cause the splint to become unusable and usually does not occur until after the 4th week of use, if at all. PMID- 3091722 TI - Button wires in the treatment of mandibular fractures. AB - Button wiring has been used as an alternative to eyelet wiring in the Department of Oral and Dental Surgery of Birmingham General Hospital since 1977. This clinical update reviews 65 patients with mandibular fractures in which button wires were utilised in their treatment. PMID- 3091723 TI - Carcinoembryonic antigen in mucoceles of oral mucosa. AB - Immunohistochemical detection of carcinoembryonic antigen (CEA) was reported in mucocele and associated minor salivary glands of oral mucosa. Higher levels of staining for CEA occurred in salivary glands with attached mucoceles, in which acinar cells and ductal segments in the gland displayed concentrations of CEA higher than those in normal minor salivary glands. Floating cells also gave positive CEA staining, whereas epithelial fragments and connective tissue in the mucocele wall were lacking in CEA. It was suggested that mucoceles in oral mucosa accumulated CEA in associated minor salivary glands. PMID- 3091724 TI - Lingual thyroid. A clinical and postmortem study. AB - 3 patients with lingual thyroid are reported. In addition, 5 patients are described with hypothyroidism in whom functioning thyroid tissue was only present at the base of the tongue without any noticeable swelling. In a postmortem study of 120 tongues, not a single case of lingual thyroid was encountered. The preponderance of females among cases of congenital hypothyroidism and/or lingual thyroid is discussed. PMID- 3091725 TI - Reinnervation of teeth after segmental osteotomy. AB - The reinnervation of 8 canine teeth denervated by segmental osteotomy has been investigated in cats by using electron microscopy. 12 weeks after osteotomy, the mean total number of axons at the canine apices was 36% of that found in normal animals. The myelinated axons were smaller than normal with thinner myelin sheaths. In non-myelinated fibres, there were fewer axons per fibre (Remak bundle) and more fibres containing only one axon. The proportions of myelinated and non-myelinated fibres were normal. PMID- 3091726 TI - Apparatus for simulating extraction forces. AB - The extraction forces can be stimulated using a mean value indicator, extraction forceps and a phantom skull. The rocking and twisting moments occurring during "extraction" can be measured with strain gauges. Before beginning practical work on patients, dental students carried out simulated extractions of various teeth. The moments were significantly lower than forces needed for real extractions. When using the simulator, the students must be supervised by a teacher able to demonstrate the correct grips of forceps handles and the correct style in extraction. PMID- 3091727 TI - Correction of jaw deformities subsequent to treatment of acromegaly. AB - In acromegaly, growth of facial bones and changes of oral and laryngeal mucosa are well accepted facts. Orthognathic surgical procedures should in these cases be postponed until the acromegalic process is well controlled. 2 cases of mandibular osteotomies (patients aged 61 and 38 years) are reported. The surgical procedures and the postoperative course of these patients were uneventful and did not deviate from those of otherwise healthy patients. PMID- 3091728 TI - The recalcitrant keratocyst. AB - The clinical enigma of appropriate management of the odontogenic keratocyst is a continuing controversy. The understanding of the pathology of the lesion has undergone a significant metamorphosis over the past 30 years. Certain research findings with respect to this lesion have set it apart from the classical odontogenic cyst, while histologic and clinical observations have made its behaviour reminiscent of the ameloblastoma. Despite its benign nature, its high recurrence rate begs the question of adequacy of treatment modalities to date. Fascinating theories have been put forward to account for its apparent resistance to conventional cyst therapy. Despite this, however, there is no unanimity as to pathogenesis or correct treatment methods. The case of a large odontogenic keratocyst of the mandible is reported and a detailed narrative of its apparently successful management by relatively conservative means is documented. PMID- 3091729 TI - Nodular fasciitis of the upper labial fascia: cytometric and ultrastructural studies. AB - The rare case of nodular fasciitis in the upper labial fascia is reported. Light microscopic, electron microscopic and cytometric studies were performed. The histopathology corresponded to intermediate and reactive types in the Price and Bernstein classification. Cytometric study of evaluating DNA of fibroblasts revealed a high distinct peak in myxoid and inflammatory areas. Ultrastructurally, fibroblasts and myofibroblasts were identified in the lesion. Reported Japanese cases of orofacial nodular fasciitis are reviewed and compared with the European-American literature. PMID- 3091730 TI - Adenomatoid odontogenic tumor associated with calcifying epithelial odontogenic tumor. AB - A case of odontogenic tumor which contained areas diagnostic for both adenomatoid odontogenic tumor and calcifying epithelial odontogenic tumor arising in the upper left anterior region in a 17-year-old Japanese female is reported. The histopathological observation suggested that the lesion represented primarily adenomatoid odontogenic tumor in which multiple foci of calcifying epithelial odontogenic tumor had developed. PMID- 3091731 TI - Complete median cleft of the upper lip and alveolus with holoprosencephaly. AB - A case of complete median cleft of the upper lip and alveolus with holoprosencephaly is presented. An 8-month-old girl was successfully treated by closure of the median upper lip. In addition, 9 patients who have undergone cheiloplasty of complete median cleft of the upper lip with holoprosencephaly reported in the Japanese literature, are reviewed. PMID- 3091733 TI - Congenital parotid gland fistula. AB - A rare case of congenital parotid gland fistula is reported. A 4-year-old boy presented with a fistula opening at the facial surface of the skin posterior to the left commissure of the lips. This fistula originated from an accessory parotid gland with a duct entirely distinct from the original Stensen's duct. Because of the salivary outflow from the fistula opening, the opening was translocated to the oral cavity using Delore's method. PMID- 3091732 TI - Primary haemangiosarcoma of the tongue. AB - A 52-year-old male had a biopsy done from a tongue lesion and was reported to have primary haemangiosarcoma. The case has been reported because of the rarity of this tumour. PMID- 3091734 TI - Lymphocytic lymphoma of the oral cavity and skeletal myeloma. AB - A 50-year-old woman had a fleshy lesion in her right buccal maxillary sulcus. This was shown to be a lymphocytic lymphoma. Further investigation also revealed multiple myeloma. The presence of 2 separate disease processes, which may have a common origin in the cells of the lymphoreticular system, is unusual. PMID- 3091735 TI - Nodular fascitis of the mandible in a child. AB - Nodular fascitis is an unusual, tumor-like, proliferative, fibroblastic lesion with infiltrative properties. We describe a case of nodular fascitis appearing in the mandible of a 2-year-old boy. A brief review of the literature on this lesion arising from intra or perioral regions, and the importance of differential diagnosis for this lesions are discussed. PMID- 3091736 TI - Intra-oral benign solid oncocytoma. AB - Oncocytomas are extremely uncommon in the intra-oral minor salivary glands, they are rarely reported in the literature and the histopathology and clinical details are inadequately documented. This has led to uncertainty with regard to the behaviour and prognosis of this type of lesion. A case of benign solid oncocytoma arising from intra-oral minor salivary glands is reported here with a brief review of the pertinent literature. PMID- 3091737 TI - [Study on the correlation between self-priming effect of LH-RH and luteal insufficiency by LH-RH two step test]. AB - To clarify not only the releasing function but the self-priming effect of gonadotropins in the anterior pituitary gland, two step administration of 100 micro-grams of synthetic LH-RH at a 60 minute interval (LH-RH two step test) was investigated in 19 women with luteal insufficiency, 7 women in puerperium (3rd 10th postpartum) and 6 women immediately after first ovulation following spontaneous abortion (pregnancy 5-7 weeks). In the luteal phase, blood samples were drawn at 0', 30', 60', 90', 120' and 180' after first LH-RH stimulation for measurement of serum LH and FSH by radioimmunoassays. delta 1 standing for hormone release = 1st peak level -0' level. delta 2 standing for selriming effect = 2nd peak level -60' level. delta 1 delta 2 ratio = delta 2/delta 1. In the luteal insufficiency group, delta 1 was significantly higher and delta 1 delta 2 ratio was lower than those in the control group. In the puerperium group, delta 1 and delta 2 responses were not detected, suggesting marked depression of the pituitary function by pregnancy. In the aborted group delta 1 and delta 2 were similar to those in the control group, indicating rapid recovery of the pituitary function. This study demonstrated that the LH-RH two step test was useful in evaluating luteal function by measuring gonadotropins. PMID- 3091738 TI - [Pathogenesis and conservative therapy of uterine leiomyoma]. PMID- 3091739 TI - [A case of male pseudohermaphroditism due to 17 alpha-hydroxylase deficiency with high levels of plasma aldosterone and angiotensin II]. PMID- 3091741 TI - [Infant and juvenile gynecology; endocrinological study and present status of juvenile pregnancy]. AB - Three topics were reviewed and our recent study on juvenile menstrual disorders was presented. Endocrinology of puberty and mechanism of onset of puberty: Review. Menstruation and its disorders during puberty. Age of menarche at present was investigated with 7,400 high school girls. No advance of menarche was recognized compared with that of 10 years ago. The rate of irregular menstruation was similar to that of 20 years ago. High occurrence of LH and testosterone increase was recognized among juvenile menstrual disorders. The prognosis of high LH/androgens girls was poor when followed for 5.6 years. Sexual activity among young girls keep increasing. Participation of gynecologist in sexual education was discussed. PMID- 3091740 TI - [Molecular genetic studies on the immune system: an approach to a clinical application]. AB - It is the function of the immune system to recognize and neutralize numerous antigens invading animals. The more diverse the antigen recognition of the organism, the more efficient is its defense system. There are two types of antigen recognition molecules in the immune system; the immunoglobulin produced by B cells and the T cell antigen receptor. These molecules have variable (V) regions which recognize antigens and constant (C) regions which mediate physiological functions. The latter provide additional diversity to the immune system. For example, the same heavy chain (H) V regions recognizing influenza hemagglutinin are expressed as the mu, gamma, epsilon, and a chains, each of which constitutes a different class of the immunoglobulin. Since the V and C regions are encoded by separate sets of DNA segments, it is the genetic variability of the V gene that determines the antigen recognition diversity. Recent molecular genetic studies on the immunoglobulin gene and the T cell antigen receptor gene indicate that the V region genes of both molecules produce somatic as well as evolutionary variations. Somatic variations include joining of two or three germ-line segments by site-specific recombinations and somatic base replacements. Evolutionary variations include gene duplication, segment transfer (gene conversion), mutational drifts, and so on. Since genetic events, be it somatic or evolutionary, tend to be random, not only useful but also harmful immunoglobulins are produced. Therefore, appropriate selection, be it positive or negative, is a prerequisite for the proper function of the genetic diversity of the immune system as the defense mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091742 TI - [Experimental studies on the ossification of the posterior longitudinal ligament of the cervical spine]. AB - Fluor, which is a natural substance contained in rice, vegetables, marine products and some seasonings, is assimilated into the body through ingestion. Approximately 60% of the total amount of this fluor intake would be based on rice. A histological study of cervical spine, knee ligaments, Achilles tendon and viscera of rabbits (approx. 12-16 weeks old) was made after injection with sodium fluoride in this study. The rabbits were divided into three groups: Group A (administered NaF 86.2 mg/kg, 5.7 mg/ml, 7 rabbits); Group B (administered NaF 31.5 mg/kg, 2.85 mg/ml, 6 rabbits) and a Control Group of 3 rabbits. Five rabbits in Group A (71.4%) and all six rabbits in Group B (100%) developed ossification of the posterior longitudinal ligament. Ossification of the yellow ligament was also found in two rabbits in Group A and one in Group B. No ossification was found in the Control Group. Both enchondral and intramembranous ossification were found in ossification of posterior longitudinal ossification in the rabbits. PMID- 3091743 TI - [Morphologic and metabolic studies on the effect of ethane-1-hydroxy-1, 1 diphosphonate (EHDP) on the epiphyseal plate and metaphysis of the rat]. AB - Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) has been widely used in recent clinical and laboratory investigations. The author examined epiphyseal and metaphyseal morphology as well as cartilage matrix and calcium metabolism during EHDP administration and after drug discontinuation by 35S, 45Ca and 3H-thymidine autoradiographic study. The effect of low-dose EHDP was limited to osteoclast dysfunction of the metaphysis with resultant widening of trabeculae. High dose administration of EHDP induces a variety of disorders with a manifestation of marked widening of the epiphyseal growth plate. This process is probably derived from a reduction in matrix calcification that relates an inhibition of chondrocyte metabolism with a resultant decreased rate of chondroitin sulfate turnover. Furthermore, high dose EHDP causes a metaphysis which exhibits rickets+ like changes with little calcification and a decrease in the normal rate of osteoprogenitor cell differentiation to osteoblasts and osteocytes. PMID- 3091744 TI - Role of glutathione in protecting endothelial cells against hydrogen peroxide oxidant injury. AB - To determine the mechanism responsible for the enhanced susceptibility of endothelial cells to oxidant injury in the absence of glucose, we induced endothelial cell injury with oxygen radicals in the presence of various oxygen radical scavengers and measured endothelial cell levels of glutathione after oxidant injury in the presence and absence of glucose. Endothelial cells were damaged with toxic oxygen radicals generated by phorbol myristate acetate (PMA) activated polymorphonuclear leukocytes (PMNs) or xanthine-xanthine oxidase in the presence and absence of glucose and catalase (scavenger of hydrogen peroxide), superoxide dismutase (scavenger of superoxide radical), isoleucine, valine, and serine (scavengers of hypochlorous acid), or mannitol, ethanol, benzoic acid, dimethyl sulfoxide, and dimethyl thiourea (scavengers of hydroxyl radical). Endothelial cell injury was quantitated by 2-deoxy-[1-3H] glucose or chromium 51 release assays or both. In each oxidant-generating system, in the presence and absence of glucose, only catalase significantly protected endothelial cells from oxidant injury (P less than 0.001). When endothelial cells were damaged by hydrogen peroxide generated with xanthine-xanthine oxidase in the presence of glucose, endothelial cell levels of glutathione remained unchanged. In contrast, when endothelial cells were damaged with xanthine-xanthine oxidase in the absence of glucose, endothelial cell levels of glutathione fell to less than 50% of baseline (P less than 0.05). Xanthine-xanthine oxidase-mediated endothelial cell damage and depletion of glutathione in the absence of glucose were similar to results obtained in the presence of glucose when glutathione was depleted with buthionine sulfoximine, diethyl maleate, or 1-chloro-2,4-dinitrobenzene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091745 TI - Inhibition of canine platelet aggregation by barbiturates. AB - The ability of barbiturates to affect in vitro platelet aggregation of canine platelets was examined. Platelet-rich plasma was incubated with thiamylal, pentobarbital, and barbital for 10 minutes before the addition of the aggregating stimulus. All three barbiturates produced a concentration-related inhibition of platelet aggregation induced by adenosine diphosphate (ADP) and collagen. The inhibitory effect of the barbiturates could not be overcome by increasing the concentration of extracellular calcium. In contrast to ADP- and collagen-induced aggregation, no inhibitory effect was observed on aggregation initiated by A23187, 12-O-tetradecanoylphorbol-13-acetate, or phospholipase C. In further studies, the ADP-induced rise in free cytosolic calcium was blocked by the barbiturates. These findings suggest that barbiturates may interfere with the rise in internal calcium associated with agonist-receptor stimulation of platelets. PMID- 3091746 TI - High performance liquid chromatography and time-of-flight secondary ion mass spectrometry: a new dimension in structural analysis of apolipoproteins. AB - We report the isolation and characterization of an apolipoprotein A-I mutant using a new technique for structural analysis of apolipoproteins based upon the combined techniques of protein isolation by isoelectric focusing in immobilized pH-gradients, reversed-phase HPLC of tryptic peptides, and subsequent molecular weight analysis of isolated peptides by time-of-flight secondary ion mass spectrometry (TOF-SIMS). The particular advantages of the TOF-SIMS procedure in the characterization of proteolytic peptides are the detection limits in the picomole range, the accuracy of molecular weight determination (up to 3000 +/- 1 D), the speed of analysis, and the wide range of applications for involatile biomolecules. The described procedure for the analysis of apolipoproteins requires only 2 ml of serum as starting material. This method can be used to monitor for genetic polymorphisms and posttranslational modifications on a microscale basis. Applying these techniques, we characterized a new apolipoprotein A-I mutant with an amino acid exchange arginine177 by histidine. PMID- 3091747 TI - An assessment of the enzyme-linked immunosorbent assay (ELISA) for diagnosis of pulmonary tuberculosis. PMID- 3091748 TI - Pleural fluid to blood glucose ratios and pleural fluid pH, pCO2, glucose relationship: a report of 144 cases. PMID- 3091750 TI - Measurement of exogenous and endogenous inhibin in sheep serum using a new and extremely sensitive bioassay for inhibin based on inhibition of ovine pituitary FSH secretion in vitro. AB - An extremely sensitive and reliable bioassay for inhibin based on inhibition of ovine pituitary FSH secretion in vitro was developed and used to measure exogenous and endogenous inhibin activity in the ewe. The sheep inhibin bioassay is 30- to 40-fold more sensitive than conventional rat inhibin bioassays. The minimum sensitivity of each bioassay in the measurement of inhibin activity in 1 ml of sheep serum is 220 mu. and 4080 mu. in the sheep and rat bioassays respectively. This sensitive inhibin bioassay has permitted, for the first time, the measurement of endogenous inhibin in the peripheral and ovarian vein blood of the sheep, as well as exogenously administered inhibin. The half-life of exogenously administered ovine inhibin (in follicular fluid) in the sheep was calculated as two components (18-24 and 50-60 min) from the inhibin profiles of six ewes. Inhibin contained in the ovine follicular fluid, given as a bolus i.v. injection, increased to maximum levels after 5 min and then remained increased for 10-32 min depending upon the dose administered, before exponentially decaying. The time for inhibin to exert its effect ranged from 3 to 6 h after injection and appeared to be dose-related. The bolus injection of inhibin, apart from causing suppression of FSH, evoked a large rebound increase of FSH up to 400% of preinjection levels. The development of the sheep bioassay will allow the measurement of biologically active inhibin in the peripheral circulation and ovarian vein blood of sheep with the possibility of extending this to man. PMID- 3091749 TI - Initiation of ovarian follicular maturation without a surge of FSH in cyclic rats treated with antiserum to LH-releasing hormone. AB - The relationship between a surge of FSH and the initiation of follicular maturation was examined using rats with a 4-day oestrous cycle. When antiserum against LH-releasing hormone (LHRH-AS) was given at 13.00 h on the day of pro oestrus (day 0), surges of FSH and LH were blocked. Plasma FSH and LH were maintained at low basal levels without a surge release until the next spontaneous surge occurred on the afternoon of day 4, the predicted day of pro-oestrus. Follicular responsiveness to an injection of human chorionic gonadotrophin (hCG) indicated that preovulatory follicles, present at the time of treatment with LHRH AS, were capable of ovulating on day 1 but had regressed by day 2. Subsequently, as shown by the ovulatory response to hCG, a new set of follicles had begun to mature by the morning of day 3 without a preceding surge of FSH. Changes in oestradiol-17 beta levels in the plasma throughout the oestrous cycle were the same in rats injected with LHRH-AS or non-immune control serum. The mature follicles in the rats treated with LHRH-AS thus retained the capacity to ovulate after losing their ability to secrete oestrogen. These results suggest that an FSH surge is not essential for initiation of follicular maturation and that basal levels of FSH may be enough to initiate follicular maturation in the absence of newly formed corpora lutea. PMID- 3091751 TI - Increase in DNA polymerase alpha activity associated with DNA synthesis due to FSH or oestrogen in ovaries of immature rats. AB - DNA polymerase activities and DNA content of ovaries from immature intact rats (4 29 days after birth), hypophysectomized rats and hormone-treated hypophysectomized rats were measured. During normal ovarian growth DNA polymerase alpha activity and DNA content of ovaries increased. The polymerase activity decreased gradually after hypophysectomy without any alteration in the DNA content. Administration of ovine FSH (2 micrograms/day) or oestradiol-17 beta (1 mg/day) to hypophysectomized rats enhanced ovarian DNA content and DNA polymerase alpha activity, whereas DNA polymerase beta activity did not change significantly. These results suggest that DNA polymerase alpha participates in DNA synthesis in these ovaries. The specific activity of DNA polymerase alpha (the activity per microgram DNA) in the ovaries increased between 4 and 14 days after birth, and then remained almost constant; the specific activity declined gradually after hypophysectomy. Administration of FSH or oestradiol-17 beta but not of ovine LH, progesterone or testosterone to hypophysectomized rats restored the specific activity. Mixing experiments with different kinds of ovarian extracts suggested that no activators of DNA polymerase alpha were present in the extracts. These results suggest that FSH or oestrogen causes the induction of DNA polymerase alpha accompanied by DNA synthesis during cell proliferation in ovaries of immature rats. PMID- 3091752 TI - Services for stroke patients one year after stroke. AB - The use of community services by stroke patients was investigated one year after their stroke. Survivors from a register of all patients from a defined community were followed up one year after their stroke. Four hundred and thirty six of the 492 survivors were seen: 301 lived at home with someone, 82 lived at home alone, and 53 were in long-stay care. One hundred and forty seven (38%) of those at home were visited by one or more community services, the major ones being district nurse (73), home help (73), day centres (42), and meals on wheels (30). Analysis suggests that these services reach the patients who need most help. However, some 57 (19%) disabled patients are being looked after at home without any outside help. PMID- 3091753 TI - The promotion of catecholamine release in rainbow trout, Salmo gairdneri, by acute acidosis: interactions between red cell pH and haemoglobin oxygen-carrying capacity. AB - A fall in blood pH was generated either by infusion of HCl or by reducing gill ventilation and raising blood PCO2 in rainbow trout, Salmo gairdneri Richardson. The acute acidosis resulting from HCl infusion caused an increase in plasma adrenaline and noradrenaline concentrations, the adrenaline increase being proportional to the decrease in blood pH. Fish subjected to a prolonged respiratory acidosis, caused by a reduction in gill ventilation, showed no increase in catecholamines 24 h after the change in gill ventilation. We suggest that catecholamine levels increase in response to a pH decrease, but if acidotic conditions are maintained, circulating catecholamines return to low levels. There was a much smaller decrease in erythrocytic pH with a fall in plasma pH when catecholamine levels were high. This ameliorating effect of catecholamines on erythrocytic pH during a plasma acidosis maintains the oxygen-carrying capacity of the haemoglobin. If erythrocytic pH was decreased by increasing blood PCO2 in vitro, then there was a fall in haemoglobin oxygen-carrying capacity which was proportional to the reduction in pH. We conclude that catecholamines are released into the blood in proportion to the fall in blood pH but if the pH is maintained the circulating catecholamines return to their initial low levels. The elevated catecholamine concentrations in blood safeguard against any impairment of haemoglobin oxygen-carrying capacity by maintaining erythrocytic pH in the face of a plasma acidosis. PMID- 3091754 TI - A triphasic ventilator for reptiles. PMID- 3091755 TI - Intracellular and extracellular acid-base status and H+ exchange with the environment after exhaustive exercise in the rainbow trout. AB - Exhaustive exercise induced a severe short-lived (0-1 h) respiratory, and longer lived (0-4 h) metabolic, acidosis in the extracellular fluid of the rainbow trout. Blood 'lactate' load exceeded blood 'metabolic acid' load from 1-12 h after exercise. Over-compensation occurred, so that by 8-12 h, metabolic alkalosis prevailed, but by 24 h, resting acid-base status had been restored. Acid-base changes were similar, and lactate levels identical, in arterial and venous blood. However, at rest venous RBC pHi was significantly higher than arterial (7.42 versus 7.31). After exercise, arterial RBC pHi remained constant, whereas venous RBC pHi fell significantly (to 7.18) but was fully restored by 1 h. Resting mean whole-body pHi, measured by DMO distribution, averaged approx. 7.25 at a pHe of approx. 7.82 and fell after exercise to a low of 6.78 at a pHe of approx. 7.30. Whole-body pHi was slower to recover than pHe, requiring up to 12 h, with no subsequent alkalosis. Whole-body ECFV decreased by about 70 ml kg-1 due to a fluid shift into the ICF. Net H+ excretion to the water increased 1 h after exercise accompanied by an elevation in ammonia efflux. At 8-12 h, H+ excretion was reduced to resting levels and at 12-24 h, a net H+ uptake occurred. Lactate excretion amounted to approx. 1% of the net H+ excretion and only approx. 2% of the whole blood load. Only a small amount of the anaerobically produced H+ in the ICF appeared in the ECF and subsequently in the water. By 24 h, all the H+ excreted had been taken back up, thus correcting the extracellular alkalosis. The bulk of the H+ load remained intracellular, to be cleared by aerobic metabolism. PMID- 3091757 TI - Long-term humoral unresponsiveness in vivo, induced by treatment with monoclonal antibody against L3T4. AB - mAbs directed against the L3T4 molecule administered in vivo caused a severe and long lasting helper cell depletion in mice. Regeneration of the L3T4+ subpopulation occurred gradually (2-3 mo) after a single antibody treatment. Experiments were designed to examine the humoral immunocompetence of such anti L3T4-treated animals during and after regeneration of the L3T4+ T cell subset. The animals were injected with anti-L3T4, immunized with soluble antigen, and challenged with antigen every 2 wk. Antibody responses to two antigens, sperm whale myoglobin (SpWMb) and KLH, which differ with regard to their immunogenicity, were compared. The lack of humoral immune responsiveness to either of these two antigens shorty after anti-L3T4 treatment responsiveness to either of these two antigens shortly after anti-L3T4 treatment was probably due to clonal depletion. The anti-L3T4-induced immunosuppressive effect on antibody production seemed to be determined in part by the preexisting T cell repertoire, as was suggested by the recovery of responsiveness to the highly immunogenic antigen KLH and the transient inhibitory effect of anti-L3T4 treatment in primed animals. The regenerating L3T4+ T cell subpopulation was relatively incompetent in initiating B cell responses. More than 40% of the L3T4+ T cell compartment had to recover to provide help for the production of anti-KLH antibodies, whereas elimination of 90% of the L3T4+ helper cells did not inhibit a primary anti-KLH response. Evidence for a heterogeneous composition of the L3T4+ subset came from experiments using rIL-2 in vivo. The addition of rIL-2 during early helper cell depletion improved the recovery of the humoral responsiveness without apparently affecting the kinetics of the regeneration of L3T4+ T cells. Interestingly, humoral unresponsiveness to the weakly immunogenic antigen SpWMb persisted for at least 120 d. This long lasting unresponsiveness could not be explained by clonal depletion, and suggested as one possibility that the presence of antigen during regeneration of the L3T4+ helper cell population may have influenced the ultimate T cell repertoire. PMID- 3091758 TI - Lectin binding to newt epidermis: fluorescent localization and effects on motility. AB - The ability of seven lectins to bind to newt epidermal cells and influence their motility was examined. Of the seven fluoresceinated lectins applied to frozen sections containing intact newt skin and migrating epidermis (wound epithelium), only Con A (concanavalin A), WGA (wheat germ agglutinin), and PNA (peanut agglutinin) produced detectable epidermal fluorescence. Con A and WGA each heavily labeled all layers of intact epidermis, but PNA bound only to the more superficial layers. In contrast to a single population of labeled cells in migrating epidermal sheets after treatment with Con A, there were both labeled and unlabeled cells after exposure to either WGA or PNA. The wound bed was labeled by both Con A and WGA, but not by PNA. DBA (Dolichos bifloris agglutinin), RCA I (Ricinus communis agglutinin), and UEA (Ulex europaeus agglutinin), did not produce significant fluorescence with either migrating or intact epidermis. In general, inhibitory effects on epidermal motility correlated with the binding studies. Thus, Con A, WGA, and PNA, the lectins which clearly bound to the epidermis, all produced a concentration-dependent depression in the rate of epidermal wound closure. RCA was somewhat paradoxical in that it was moderately inhibitory despite showing essentially no binding. The effects of SBA and UEA were equivocal. DBA had no effect. These results indicate that the inhibition of motility produced by Con A that we have described previously is not peculiar to this mannose-binding lectin, but is shared by at least one lectin with an affinity for D-GlcNAc (WGA), and one with an affinity for B-D-Gal(1-3)-D GalNAc (PNA).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091756 TI - Cloning of the structural genes of three H8 antigens and of protein III of Neisseria gonorrhoeae. AB - A bank of gonococcal DNA was constructed in the lambda gt11 expression vector. immunological screening of the bank resulted in the isolation of a clone that contains the structural gene of protein III. In addition, several clones reactive with mAbs specific for the H8 antigen were isolated. DNA hybridization studies revealed that these H8-reactive clones were derived from three different gonococcal genes. When the products produced by these clones were used to absorb antibodies from a rabbit antiserum, and the eluted antibodies were used in immunological studies, it could be shown that the parent gonococcus expressed the product of two of these H8 genes, and in strain R10, these had Mr of approximately 19,700 21,200 respectively. The larger form has not been recognized hitherto because the epitope reactive with the H8 mAb may be masked in this product. PMID- 3091759 TI - The MPTP story: an introduction. PMID- 3091760 TI - The actions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in animals as a model of Parkinson's disease. AB - The ability of MPTP to induce persistent parkinsonism in man may provide a vital clue to the cause of the idiopathic disease. However, the peripheral administration of MPTP to rodent species only produces losses in brain dopamine content and damage to the nigrostriatal system in high doses and no persistent motor deficits have been observed. In contrast, in primates, the administration of MPTP rapidly induces a persistent parkinsonian syndrome accompanied by evidence for selective damage to the nigro-striatal dopamine containing system. Other neurotransmitter systems appear unaffected by MPTP treatment. The MPTP treated primate responds to the administration of L-DOPA and other antiparkinsonian drugs and may provide a useful test-bed for the development of novel antiparkinsonian medication. Administration of MPTP to primates causes an accumulation of MPP+ in a variety of brain areas. The accumulation of MPP+ and the neurotoxic actions of MPTP in primates can be prevented by the prior administration of monoamine oxidase inhibitors. The ability of monoamine oxidase inhibitors to prevent MPTP toxicity is related to the metabolism of MPTP by monoamine oxidase B, probably extraneuronally in glia, to produce MPDP+ and subsequently MPP+. In rodent synaptosomal preparations MPP+ is a substrate for the dopamine uptake mechanism and so would be selectively accumulated in brain dopamine neurones. Administration of MPTP to animals results in the production of a partial model of idiopathic Parkinson's disease as it occurs in man. MPTP treatment produces the major symptoms of Parkinson's disease in primates but the pathology is limited to the nigro-striatal system, whereas in Parkinson's disease pathology is more widespread. Biochemical changes induced by MPTP again seem primarily limited to those induced by damage to the nigro-striatal dopamine containing system. MPP+ (or another metabolite of MPTP) may be responsible for the neurotoxicity of MPTP but not all neurones which accumulate products of MPTP metabolism are damaged. The nigro-striatal system may be peculiarly sensitive to the effects of MPTP. PMID- 3091761 TI - Neuropharmacological manipulations with MPTP. AB - Studies have been carried out in the rodent and marmoset to assess (i) the selectivity of MPTP action to the nigrostriatal system, (ii) the possibility that melanin pigmentation may influence the actions of MPTP, (iii) whether the metabolites of MPTP may contribute to its actions on dopamine cells, (iv) the site(s) of action of MPTP in the brain, (v) the mechanism(s) of action of MPTP and whether it is possible to prevent the damaging effects of MPTP/metabolites on the brain dopamine systems. The peripheral administration of MPTP in the mouse causes depletions of dopamine and its metabolites in both the striatal and limbic systems: this action is similar in both white and pigmented mice. The MAO-B inhibitor deprenyl was shown to antagonize the actions of MPTP, and its metabolite formed via oxidation through MAO, MPP+, was shown to disrupt striatal dopamine function as determined behaviorally (as motor impairment) or biochemically (as loss of dopamine and its metabolites) when injected into the cerebral ventricles of mouse or infused into the substantia nigra of rat brain. MPTP and MPP+ act in the midbrain to interfere with dopamine cell functioning, and studies in both the rodent and marmoset are presently analyzing possible additional actions in forebrain regions. It is therefore proposed that the neurotoxic action of MPTP, effected via its metabolite MPP+, may not be selective for the nigrostriatal system. Nevertheless, the nature and profile of neurotoxicity effected by MPTP and, in particular, MPP+ should ensure continuing analyses of the relevance of such action to an understanding of the etiology of, treatment of, and even the possible prevention of Parkinson's disease in man. PMID- 3091762 TI - The role of MAO in MPTP toxicity--a review. AB - MPTP is oxidized to its toxic metabolite MPP+ by MAO B in both primate and rodent brains and this reaction can be inhibited by (-)-deprenyl. MPTP can also act as an inhibitor of both MAO A and B. There is some evidence that MAO B is localized predominantly in glia, and this would explain why dopamine uptake blockers also can prevent MPTP toxicity. The possibility that molecules with a similar action to MPTP cause idiopathic Parkinson's disease is discussed. PMID- 3091763 TI - MPTP: clinical implications. AB - The concept of selective vulnerability of the basal ganglia is briefly reviewed historically, with respect to the possible implications of MPTP and also the possible protective effects of selective MOA inhibition in the treatment of Parkinson's disease. PMID- 3091764 TI - In vivo voltammetric monitoring of catecholamine metabolism in the A1 and A2 regions of the rat medulla oblongata. AB - Catecholaminergic metabolism was estimated in A1 and A2 noradrenergic nuclei of the rat medulla oblongata using differential normal pulse voltammetry combined with electrochemically treated carbon fiber microelectrodes. In both areas an oxidation peak appearing at +50 mV was recorded. Electrochemical data and pharmacological experiments indicated that 3,4-dihydroxyphenylacetic acid (DOPAC) synthesized by noradrenergic neurons was the major contributor to this signal. Indeed, alpha-methyl-p-tyrosine, by inhibiting tyrosine hydroxylase, and pargyline, by inhibiting monoamine oxidase, both totally suppressed the peak appearing at +50 mV in A1 and A2 areas. Conversely, FLA-63, an inhibitor of dopamine-beta-hydroxylase, increased it. Moreover, a local and unilateral injection of catecholaminergic neurotoxin (6-hydroxydopamine) in the vicinity of A1 induced a 60% decrease in the peak height. This effect was prevented by pretreatment with desipramine, an inhibitor of noradrenaline reuptake, which is known to protect noradrenergic neurons against the action of 6-hydroxydopamine. Finally, specific drugs acting on alpha-2-noradrenergic receptors (clonidine and piperoxane) modulated the peak height recorded from both structures. Thus, as previously shown in the locus ceruleus, the variations in the extracellular DOPAC levels reflect the metabolic activity of A1 and A2 noradrenergic neurons. PMID- 3091765 TI - Investigation of dopamine content, synthesis, and release in the rabbit retina in vitro: I. Effects of dopamine precursors, reserpine, amphetamine, and L-DOPA decarboxylase and monoamine oxidase inhibitors. AB - The basal catecholamine content of rabbit retina was determined by liquid chromatography with electrochemical detection (LC-EC) and 3,4 dihydroxyphenylethylamine (dopamine, DA) found to be the major catecholamine. The immediate DA precursor, 3,4-dihydroxyphenylalanine (L-DOPA), and the metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), were also detected at about 2.8% and 17% of DA levels, respectively. When added exogenously, L-tyrosine did not increase the rate of DA synthesis over the basal level. In contrast, exogenous L-DOPA led to a 3.5-fold increase in DA, and to a 20-fold increase in DOPAC content. The monoamine oxidase inhibitors pargyline and (-)-deprenyl differentially affected the degradation of DA, since 100 microM pargyline was apparently more effective than 100 microM (-)-deprenyl. Reserpine and (+/-)-amphetamine each induced a Ca2+ independent decrease of DA stores. The separate actions of reserpine and (+/-) amphetamine in lowering tissue DA levels were additive, suggesting two separate pools of DA available for release from presynaptic stores. The present study demonstrates that the LC-EC technique may be used to investigate the modulation of the synthesis and release of retinal DA in vitro, without the prior uptake of radiolabelled transmitter. PMID- 3091766 TI - Aging decreases the sensitivity of rat cortical synaptosomes to calcium ionophore induced acetylcholine release. AB - The capacity of calcium ions to trigger acetylcholine release was studied in cerebral cortical synaptosomes from adult (6-month-old) and senescent (24-month old) rats, using a calcium ionophore, A23187, that bypasses voltage-sensitive calcium channels. The potency but not the efficacy of the A23187 was reduced with respect to releasing acetylcholine (ACh) in the aged animals. There was no age related difference in the synthesis of ACh or potency of the ionophore with respect to increasing 45calcium uptake. These results suggest that aging reduces the sensitivity of cerebral cortical nerve terminals to calcium-triggered ACh release. PMID- 3091767 TI - Expression of synaptophysin during postnatal development of the mouse brain. AB - The expression of the synaptic vesicle membrane protein, synaptophysin, was analyzed during postnatal development of the mouse cerebrum using a quantitative immunoblotting procedure. From birth to adulthood, the relative contents of synaptophysin increased 80-fold, reaching a final level of 3.5 micrograms/mg of total protein. The time course of accumulation suggests that synaptophysin expression is correlated with synaptogenesis. Thus synaptophysin may be used as a reliable marker of nerve terminal differentiation. PMID- 3091768 TI - Electrophysiological and positron emission studies in a patient with cortical myoclonus, epilepsia partialis continua and motor epilepsy. AB - A patient is described who had a combination of stimulus-sensitive cortical myoclonus, epilepsia partialis continua, and Jacksonian motor epilepsy. He eventually required surgery because of the severity of his seizures. Electrophysiological recordings made before and during surgery, and PET scans performed before surgery identified an abnormal area of cerebral cortex in the postcentral parietal region. It is suggested that the stimulus-sensitive myoclonus arose because input into this region from peripheral sensory afferents produced an abnormal discharge which was fed forwards via cortico-cortical connections to the precentral motor cortex, to produce a reflex muscle jerk. The epilepsia partialis continua may have been caused by spontaneous discharges arising in the same region of parietal cortex. Both forms of jerking disappeared after resection of this part of the cortex. PMID- 3091769 TI - Free light chains in the cerebrospinal fluid. PMID- 3091770 TI - Brain dopamine metabolism in patients with Parkinson's disease measured with positron emission tomography. AB - L-[18F] fluorodopa was administered in trace amounts intravenously to healthy control subjects and to patients with Parkinson's disease. Striatal uptake of radioactivity was measured using positron emission tomography. The capacity of the striatum to retain tracer was severely impaired in patients compared to controls. This may reflect a reduction of striatal dopamine storage in Parkinson's disease. Patients showing the "on/off" phenomenon had an even greater decrease of striatal storage capacity. PMID- 3091771 TI - Reactivity of the cerebral circulation in patients with carotid occlusion. AB - Cerebral blood flow (CBF) and the response to hypercapnia (cerebral reactivity) have been measured in 41 patients with unilateral or bilateral internal carotid artery occlusion in an attempt to identify those with limited collateral reserve. Normocapnic CBF was within normal limits in the majority of subjects. The response to hypercapnia varied from normal to absent, with impaired reactivity becoming increasingly likely when more than one artery was diseased. In 19 patients with unilateral carotid occlusion, hemisphere reactivity was well preserved in the majority, but was significantly lower on the side of the occlusion (mean 2.9%/mm Hg) compared to the normal side (mean 3.4%/mm Hg). Reactivity on the side of the occlusion was further reduced in 15 patients with occlusion and contralateral internal carotid artery stenosis (mean 1.7%/mm Hg) and was even lower in seven patients with bilateral occlusion (mean 1.1%/mm Hg). There was no difference in reactivity between asymptomatic hemispheres in the 41 patients (mean 2.7%/mm Hg) and hemispheres in which a previous stroke had occurred (mean 2.8%/mm Hg). In contrast the response in hemispheres subject to continuing transient ischaemic attacks was significantly impaired (mean 1.6%/mm Hg), suggesting that the cerebral symptoms in some of these patients may have had a haemodynamic origin more often than suspected from the clinical history. PMID- 3091772 TI - EEG and serum prolactin studies in relation to transcutaneous stimulation of central motor pathways. AB - Eight adult volunteers had EEG recordings and serial serum prolactin estimations performed both before and after a session of transcutaneous stimulation of the central motor pathways using the technique of Merton and Morton. No significant changes in either the EEG traces or in the serum prolactin values were detected. PMID- 3091773 TI - Immunoglobulin allotypes and susceptibility to multiple sclerosis. An epidemiological and genetic study in the Hautes-Pyrenees county of France. AB - Serum samples collected from 69 patients with multiple sclerosis (MS) living in the Hautes-Pyrenees county were tested for immunoglobulin Gm gamma 1, gamma 2, and gamma 3, heavy chain allotypes (Gm system), and immunoglobulin light chain Kappa (Km system). A control group was made up of normal individuals living in the same county. We found a significant excess of individuals with Gm3; +/- 23;5/Gm3; +/- 23;5 amongst the MS patients as compared with controls (relative risk = 2.4). A slight increase of the Km (1) frequency was found in MS patients compared with controls, 21.7% vs 11.8%, but this difference was not significant. PMID- 3091775 TI - Congenital muscular dystrophy and cerebral CT scan anomalies. Results of a collaborative study of the Societe de Neurologie Infantile. AB - We present the results of a collaborative study on the association of congenital muscular dystrophy with central nervous system anomalies revealed by CT scan investigation of 10 patients. In seven children, an abnormal hypodensity of the cerebral white matter is found; in four of these patients, this radiological anomaly is either isolated, or associated with a moderate intellectual impairment; in one case, severe mental retardation and ocular changes had occurred; in the other two cases, the muscular disease was progressing slowly, in association with microcephaly, epilepsy, and moderate mental retardation. Three children were afflicted with a severe early encephalopathy and congenital muscular dystrophy, and presented signs of cortical and subcortical atrophy on CT scan. Two of these patients corresponded to different types of cerebro-ocular dysplasia-muscular dystrophy syndromes, and the third patient of Fukuyama's congenital muscular dystrophy. These observations are discussed and compared with those reported in the literature. The authors emphasize the need to investigate possible cerebral CT scan anomalies in congenital muscular dystrophies, and to look for muscular changes in some prenatal encephalopathies. PMID- 3091774 TI - Selective suppression of neurofilament antigen expression in the hypothyroid rat cerebral cortex. AB - As an integral component of the cytoskeleton neurofilaments play a central role in the establishment and maintenance of neuronal form. In particular, high neurofilament concentrations are characteristic of many classes of axons in the central nervous system. Isolated neurofilaments from rat brain consist of 3 distinct polypeptides with apparent molecular weights 210K, 160K and 68K. A murine monoclonal antibody, mabN210, has been produced which specifically recognizes an epitope associated with the high molecular weight subunit and this antibody has been used to explore the regulation of neurofilament expression during brain development. It has been shown that in the rat cerebellar cortex, the expression of mabN210-immunoreactivity in basket cell axons is severely suppressed in hypothyroidism while neurofilament antigen expression in other cerebellar axons seems not to require thyroid hormones. In view of the well-known cortical deficits in hypothyroidism, these studies have now been extended to include the developing rat cerebral cortex and selected cortical afferent and efferent axons. In hypothyroid rats there is a marked suppression of mabN210 immunoreactivity in the cerebral cortex and corpus callosum and, to a lesser extent, there is a reduction in staining in the internal capsule. By contrast, hypothyroidism did not reduce mabN210-immunoreactivity in the lateral olfactory tract or the stria medullaris. In rats, serum thyroid hormone starts to rise to adult levels on postnatal day 4. It appears that axons that have attained their mature distribution prior to the onset of thyroid hormone expression are not affected by hypothyroidism whereas mabN210-immunoreactivity is suppressed in those axonal tracts that reach a mature distribution after P4. PMID- 3091776 TI - Presynaptic elements formed on polylysine-coated beads contain synaptic vesicle antigens. AB - Cell cultures of the rat cerebellum were immunostained with antibodies to synaptic vesicle antigens, Synapsin I and SV48. Light microscopic immunocytochemistry showed that the initial appearance of demonstrable SV48 and Synapsin I immunoreactivity occurred at different times. Synapsin I immunostaining, unlike SV48 immunostaining, was first seen at 3 days in vitro as occasional punctate immunofluorescence in neurites, while SV48 immunostaining was first seen at 5 days in vitro. Both SV48 and Synapsin I punctate immunostaining became frequent at 7 days in vitro. Double labelling experiments showed coexistence of the above proteins in punctate swellings and growth cones. Using the electron microscope, either SV48 or Synapsin I immunostaining was demonstrated within presynaptic elements in the neuropil. When cultures were incubated with polylysine-coated beads, both types of immunostaining were found in the vesicle containing presynaptic elements formed on the bead surface. It is concluded that Synapsin I and SV48 are co-localized in the same populations of presynaptic elements, co-localized in some growth cones and found in presynaptic elements on beads. PMID- 3091777 TI - On-line computer estimation of carbon dioxide response curves. AB - Anesthesiologists are concerned with the effect of various anesthetics on a patient's central nervous ventilatory control. The most widely accepted method of determining the effect of a drug is to compare carbon dioxide response curves (delta VE/delta PETCO2, where VE = minute ventilation [in L/min] and PETCO2 = end tidal carbon dioxide [in mm Hg]) measured before and after administration of the drug. Additional information concerning neuromechanical control can be obtained by also including a measure of the airway occlusion pressure (generally measured 100 ms after occlusion, i.e., P100). To facilitate these measurements we have developed a portable, computer-controlled data acquisition system. It includes an Apple II+ computer and measures VE, PETCO2, and P100. Each subject rebreathes exhaled carbon dioxide through a two-way breathing valve attached to a 9-liter reservoir, which is initially filled with 5% carbon dioxide and balance oxygen. Exhaled carbon dioxide concentrations are measured with an infrared medical gas analyzer on samples taken through a catheter connected at the mouthpiece. The exhaled flow is measured with a pneumotachograph in conjunction with a differential pressure transducer, and P100 is determined with a Validyne MP45 pressure transducer. PMID- 3091778 TI - Chemotherapy of drug-resistant ovarian cancer: a Southwest Oncology Group Study. AB - We present a final analysis, including pathology review, of a cooperative group study of drug-resistant ovarian cancer. Of 200 patients registered, 112 were eligible and evaluable, with a response rate of 26% and median survival of 7 months. Because these results are poorer than those reported in the preliminary and interim analyses of this study, we scrutinized the 88 excluded patients, most of whom failed to meet our strict pathologic criteria for a diagnosis of ovarian cancer of epithelial type, and who, as a heterogeneous group, fared better than patients who did meet the eligibility criteria. We believe this analysis provides insight into the spectrum of diseases that are frequently called ovarian cancer, but might be more properly labeled abdominal carcinomatosis. PMID- 3091779 TI - Mitomycin C skin toxicity studies in mice: reduced ulceration and altered pharmacokinetics with topical dimethyl sulfoxide. AB - A series of toxicologic and pharmacokinetic studies were performed in BALB/c mice administered intradermal (ID) mitomycin C (MMC) at doses of .015 to 0.25 mg. Dose dependent skin ulcers were produced at clinically relevant MMC dose levels of .05 and .075 mg (3.6 to 10.7 mg/m2). These doses produced peak ulcers of 0.15 to 0.22 cm2, respectively, one to five days after injection. The integrated ulcer area X time values (area under the curve [AUC] ulceration) were 0.89 and 3.11 cm2 X d. A large number of local pharmacologic adjuvants were found to be ineffective at reducing MMC ulceration after proximal ID injection. These included diphenhydramine, catalase, heparin, hyaluronidase, hydrocortisone, cysteine, N acetylcysteine, lidocaine, vitamin E, and superoxide dismutase. Also, neither topical heating nor cooling of skin reduced MMC ulcerations. In contrast, a single topical application of a 100% dimethyl sulfoxide (DMSO) solution completely prevented 0.025 mg MMC-induced skin ulceration and significantly reduced .075 mg MMC ulceration (P less than .05 by multiple range tests). Topical DMSO also altered the disposition of ID MMC in mouse skin but not in plasma. Unexpectedly, the DMSO applications slowed MMC elimination from the skin. DMSO significantly increased the AUC for MMC in skin from 0.89 to 2.25 ng/h/mL of tissue (P less than .05). DMSO did not alter the degree of protein binding in skin tissue nor the in vitro chemical stability of MMC in skin tissue homogenates. These results show that experimental MMC-induced skin ulcers in mice can be ameliorated with an immediate application of topical DMSO. This effect is not due to enhanced systemic drug uptake, but may be due to reduced reactivity of MMC with target cellular nucleophiles. PMID- 3091780 TI - Tumours in the pineal and supra-sellar region. A review of clinical manifestations and managements. AB - The records of 14 patients with a tumour in the pineal or supra-sellar region seen at The Norwegian Radium Hospital, Oslo between 1973-1980 have been studied retrospectively. The problems with a widely accepted classification are discussed, as well as the choice of treatment (surgery versus radiation) and the indications for local or total CNS radiation. All patients should start radiation treatment to a local field with a generous margin. After 20 Gy a CT scan should be performed. A marked reduction in tumour size indicate a radiosensitive tumour (germ cell tumour or pineoblastoma) and the radiation field should be extended to total CNS who receives 30 Gy. No change on CT scan after 20 Gy indicate a tumour of glial origin or pineocytoma, the radiation should then continue with a local field to 50 Gy. PMID- 3091781 TI - Isolated frog olfactory cilia: a preparation of dendritic membranes from chemosensory neurons. AB - The recently introduced frog olfactory cilia preparation (Chen and Lancet, 1984; Pace et al., 1985) has been useful for studies of molecular chemosensory mechanisms. Here we describe in detail the properties of this cilia preparation. The "calcium shock" procedure leads to a complete removal of the cilia from the olfactory epithelial surface. Isolated cilia constitute segments of proximal regions with 9 X 2 + 2 microtubular arrangement and a large proportion of membrane vesicles, probably derived from the ciliary distal segments. Polypeptides unique to the olfactory cilia preparation, compared to a control preparation of palate respiratory cilia, are identified by Coomassie brilliant blue staining, silver staining, and radiolabeled lectin overlays, as well as by biosynthetic labeling with 35S-methionine in epithelial explants and protein phosphorylation in isolated cilia. The olfactory cilia preparation contains odorant-sensitive adenylate cyclase, which is absent in control membranes from deciliated epithelium. High activities of tyrosine and serine/threonine protein kinases are also present. The olfactory cilia preparation described should be instrumental in the further elucidation of the biochemistry and molecular biology of vertebrate olfaction. PMID- 3091782 TI - Structural similarities and differences between neurofilament proteins from five different species as revealed using monoclonal antibodies. AB - Neurofilament (NF) proteins isolated from human, rabbit, rat, and chicken spinal cord white matter were immunoblotted with monoclonal antibodies (MAbs) raised to bovine NF immunogens. The aim of these experiments was to test the degree of epitope conservation among NF proteins from different vertebrate species. In so doing, the validity of using antibodies raised to NF from one species (cow) for detecting NF proteins of other species was also tested. The MAbs used for these experiments were characterized using bovine NFs to define polypeptide specificity, the approximate location of epitopes within each NF polypeptide, and the effects on antibody recognition of the presence or absence of phosphorylated residues in these polypeptides (see Carden et al., 1985). Our findings indicate that epitopes located in the alpha-helical core domains of NF-H, NF-M, and NF-L are distinct from each other, yet are strongly conserved among the different species. Epitopes located in the noncore or peripheral domains of the NF polypeptides show variable degrees of cross-species preservation. For example, all epitopes in the peripheral domains of bovine NF-H that require the presence of phosphate groups for recognition (phosphorylation dependent) are widely expressed in all species studied. Many phosphorylation-dependent epitopes of bovine NF-H are also present in bovine NF-M, as well as in NF-H of non-bovine species. In addition, epitopes in the peripheral domain of NF-H that require dephosphorylation of NF polypeptides for recognition (dephosphorylation dependent) are also found in NF-H of other mammalian species but not in NF-H of chicken.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091783 TI - Deafferentation elicits increased dopamine-sensitive adenylate cyclase and receptor binding in the olfactory tubercle. AB - Removal of a major non-catecholaminergic output from the olfactory bulb elicits sprouting of dopaminergic axons in the olfactory tubercle. The functional consequences of this increased dopaminergic innervation are presently not known. This study examined the question of whether lesion-induced sprouting of dopaminergic axons is associated with changes in dopamine-sensitive adenylate cyclase and dopamine receptor density in the partially denervated olfactory tubercle. The results indicate that dopamine- and NaF-stimulated adenylate cyclase activity increased as early as 7 d, while forskolin-sensitive activity increased at 3 d and persisted up to 20 d after lesioning; higher levels of GTP- and NaF-stimulated enzyme activity were found in detergent extracts of olfactory tubercle membranes from 20 d lesioned rats; higher levels of 3H-forskolin binding were found in membranes from 14 and 20 d lesioned rats; and there was an increase in dopamine receptor density, but not affinity, in olfactory tubercle membranes from lesioned rats. The data indicate that lesion-induced dopaminergic sprouting in the olfactory tubercle is temporally coordinated with the increased formation of dopamine receptors, both D1 and D2, the stimulatory guanine nucleotide regulatory protein (Ns) and the catalytic subunit (C) of adenylate cyclase in the postsynaptic membrane. PMID- 3091784 TI - The role of calcium in the rapid adaptation of an insect mechanoreceptor. AB - The femoral tactile spine of the cockroach is a rapidly adapting mechanoreceptor in which the response to a step displacement is a burst of action potentials lasting about 1 sec. This adaptation seems to occur during the encoding of action potentials from receptor current, since there is no evidence of adaptation in the receptor potential, and the adaptation can be demonstrated by direct electrical stimulation of the single sensory neuron in the spine. We have recently presented evidence for a calcium-activated potassium conductance in the tactile spine receptor neuron, although it was not directly linked to adaptation. Since this conductance could be involved in the rapid adaptation of the tactile spine neuron, we sought an association between adaptation and the entry of calcium ions into the cell. Adaptation in the tactile spine neuron was examined by direct electrical stimulation using a randomly fluctuating current followed by frequency response analysis. The dynamic behavior was studied as a function of the concentration of calcium ions in the bathing solution, the presence of calcium channel blocking agents, or the divalent cation ionophore antibiotic A23187. No evidence could be found that entry of calcium ions into the cell has a major role in the sensory adaptation. PMID- 3091785 TI - CT images in constitutional abnormalities of the posterior pole of the eye: optic disc coloboma, posterior pole staphyloma. PMID- 3091786 TI - Routine synthesis of L-[18F]6-fluorodopa with fluorine-18 acetyl hypofluorite. AB - The synthesis of L-[18F]6-fluorodopa (2.4-10.6 mCi) was done by passing gaseous [18F]acetyl hypofluorite through a solution of L-methyl-N- acetyl-[beta-(3 methoxy-4-acetoxyphenyl)]alaninate in acetic acid at room temperature followed by the hydrolysis of the intermediate products with concentrated hydriodic acid. The desired fluorodopa isomer was isolated in 8% EOB radiochemical yield by high performance liquid chromatography in an overall synthesis time of 100 min. PMID- 3091788 TI - Impact of workplace characteristics on costs and benefits of medical screening. AB - This paper discusses medical screening from an economist's perspective. The benefits and costs of testing are described, including health benefits, direct costs of testing, and labor market impacts. The paper then discusses how workplace characteristics unrelated to worker health can affect the value to employers of medical screening. As a result, employers who maximize the benefits to them of medical screening may reduce the net social benefits of screening. The differences between the private and social benefits of medical screening suggest some areas where medical screening should be used with great care and others that may be the appropriate subjects of regulation. PMID- 3091787 TI - Effects of type of dietary fat and carbohydrate on gluconeogenesis in isolated hepatocytes from BHE rats. AB - The effect of type of dietary fat and carbohydrate on gluconeogenesis and ketogenesis by isolated hepatocytes was studied. BHE male weanling rats were fed one of six diets: 64% sucrose or cornstarch with 6% corn oil, 6% hydrogenated coconut oil, or a 1:2 mixture of the two oils. At 100 d of age the rats were anesthetized, and isolated hepatocytes were prepared. The cells were incubated with lactate, lactate and lysine, lactate and pyruvate, lactate and palmitate, lactate and linoleate, lactate and epinephrine or lactate and glucagon. The hepatocytes from the rats that had been fed hydrogenated coconut oil produced significantly more glucose than the rats fed either corn oil or a mixture of oils, regardless of the type of carbohydrate fed. Each of the additives in turn, except for epinephrine, stimulated glucose production above that obtained with lactate alone. However, when expressed as a percent increase above that from lactate there was no effect of fat type on the magnitude of this stimulation. We interpret these data to mean that, although the metabolic pathways function equally well in the hepatocytes isolated from rats fed hydrogenated coconut oil and rats fed corn oil, the flux through these pathways can be influenced by the type of dietary fat. PMID- 3091789 TI - Economics of notification and medical screening for high-risk workers. AB - Measuring the economic impact of notification and intervention programs for workers at high risk of disease from workplace exposure has been virtually nonexistent for several reasons, which will be discussed, and should include a comprehensive view of costs and benefits. A framework for analysis is proposed defining four major clients: the business community, workers and their families, the local and regional public sector, and the federal government. For each client, the positive and negative, quantitative and nonquantitative, direct and indirect, short-run and long-run effects are probed and a summary analysis is made. To illustrate the process, the notification and screening program conducted by the National Institute for Occupational Safety and Health and the Workers' Institute for Safety and Health, Augusta, Georgia, for workers exposed to beta naphthylamine is described. PMID- 3091790 TI - Advances in understanding cell interactions in tissue resorption. Relevance to the pathogenesis of periodontal diseases and a new hypothesis. AB - Much of the connective tissue degradation that takes place in periodontal diseases is mediated by proteolytic enzymes. Previous studies have focused on the action of proteinases released by invading polymorphonuclear neutrophils and macrophages, and bacterial enzymes. In view of recent work establishing that resident connective tissue cells can be induced by cytokines to bring about the destruction of their own matrix, we propose a new hypothesis. In this we envisage that a critical step is the interaction of bacterial antigens with inflammatory cells, resulting in the production of a cytokine, interleukin-1. Our interpretation of in vitro evidence is that the loss of connective tissue attachment and bone matrix resorption in periodontal diseases is mediated by metalloproteinases such as collagenase and stromelysin released by cells of the periodontium. Such proteolytic destruction can be induced by interleukin-1, whose production may not be dependent on a specific microbial flora but may be triggered by a number of organisms. It is now clear that interleukin-1 has multiple actions on both immune and non-immune cells; these include the induction of lymphocyte differentiation and proliferation and the stimulation of bone and cartilage resorption, and prostaglandin and metalloproteinase synthesis by connective tissues. It seems likely that further knowledge about the production and function of this cytokine will have an increasing impact in many diseases that involve resorption, particularly since interleukin-1-like molecules can be produced by cell types other than monocytes/macrophages, including keratinocytes and fibroblasts. PMID- 3091791 TI - Growth and acid production of Candida species in human saliva supplemented with glucose. AB - Growth characteristic and acid production of oral isolates of Candida albicans and Candida glabrata in glucose supplemented and glucose-free, pooled, human whole saliva were examined. Both Candida species exhibited sigmoidal growth curves in batch cultures of mixed saliva, supplemented with glucose. The growth of Candida in saliva was accompanied by a rapid decline in pH from 7.5 to 3.2 over 48 h and the major acidic components initiating and sustaining this pH drop were pyruvates and acetates. These acidic metabolites may play an important role in the pathogenesis of oral Candida infections. PMID- 3091792 TI - The effect of iron deficiency on early oral carcinogenesis in the rat. AB - In order to further investigate the known influence of iron deficiency on 4NQO oral carcinogenesis in the rat, groups of iron-deficient and iron-sufficient Charles River white rats were painted with carcinogen for 8 weeks or 14 weeks and then left untreated for 32 weeks or 26 weeks respectively. Tumour development and epithelial dysplasia were assessed at the time of killing. Animals painted for 14 weeks showed more severe dysplasia than those painted for 8 weeks, but no significant differences were noted between corresponding iron-deficient and iron sufficient groups. PMID- 3091793 TI - A semi-quantitative assessment of the histopathology of oral lichen planus. AB - In a retrospective study of 112 cases, an attempt has been made to further delineate the histopathological parameters which are useful in making a diagnosis of oral lichen planus. The results of this study show that mononuclear infiltration beneath and adjacent to the epithelium, parakeratosis and degeneration of the basal layer of the epithelium were consistent features. Linear regression analyses of the parameters studied provided partial support for a cell-mediated immune mechanism. PMID- 3091794 TI - Mast cells in oral lichen planus. AB - Biopsies from lichen planus affected oral mucosa were compared with biopsies from healthy oral mucosa, in terms of the number of mast cells, their location and their morphological alteration at the light microscopic and electron microscopic level. In comparison with the normal oral mucosa an increased number of mast cells was found below the subepithelial infiltrate. This difference was statistically highly significant (p less than 0.001). In the deeper part of the infiltrate mast cells were found to contain granules which presented an altered morphology upon electron microscopic examination. These cells had many of the ultrastructural changes that have been reported for mast cells undergoing degranulation. The present morphological observations suggest that mast cells participate in the recruitment of lymphocytes to the subepithelial infiltrate. PMID- 3091795 TI - Enhanced penetration of nitrosonornicotine across oral mucosa in the presence of ethanol. AB - There is evidence for synergy between tobacco and alcohol in the etiology of oral cancer but the reason for such an effect is unclear. One possible explanation is that alcohol enhances the penetration of carcinogens through the oral lining. We measured the permeability in vitro of three regions of porcine oral mucosa to the tobacco associated carcinogen, nitrosonornicotine (NNN) alone and in the presence of 5% or 50% ethanol. 50% ethanol did not significantly alter the permeability of oral mucosa to NNN except for buccal mucosa, where it was reduced. However, there was a significant increase in the permeability of gingiva and floor of mouth mucosa (but not buccal mucosa) in the presence of 5% ethanol; this increase occurred after far shorter exposures for floor of mouth than for gingiva. These results accord well with studies showing that the floor of mouth is a "high risk area" for oral carcinoma and that there is an increased relative risk of oral cancer for heavy smokers and drinkers and, in particular, for those individuals who consume beverages with a low alcohol content. PMID- 3091796 TI - Oral epithelial atypia and acantholytic dyskeratosis in rats painted with 4 nitroquinoline N-oxide. AB - Oral epithelial atypia and foci of acantholytic dyskeratosis (FAD) were investigated in 54 rats treated with the carcinogen 0.5% (w/v) 4-nitroquinoline-N oxide in propylene glycol and in 18 rats treated with propylene glycol only. The palate of each animal was painted 3 times weekly for up to 9 months and rats were killed at monthly intervals. A gradual significant increase in the epithelial atypia indices of the palatal and lingual tissues (anterior and posterior of the intermolar tubercle) was observed with a maximum value of 17-22 of a possible 75 at 28-32 weeks. No significant differences were noted between the atypia indices of the palatal and lingual tissues. FAD were not evident in the palate or lingual tissues before 12 weeks and 16-24 weeks, respectively, and although the palate consistently showed more FAD compared with the lingual tissues the differences were not significant. Features of epithelial atypia and FAD were absent in the 18 control rats treated with propylene glycol only and in 8 untreated control animals. At 28 weeks of 4NQO treatment 2 of 5 rats, at 32 weeks 3 of 4 rats and at 36 weeks 3 of 3 rats had developed infiltrating squamous cell carcinomas in either/both the palate or tongue. The results suggest that epithelial dysplasia and acantholytic dyskeratosis may be late morphological features of a more fundamental change occurring earlier in the process of tumour development. PMID- 3091797 TI - Ameloblastoma with myofibroblasts: first report. AB - A recurrent infiltrative ameloblastoma of the mandible with a predominantly "follicular pattern" of the epithelial component is studied. The stroma contains abundant myofibroblasts; these cells have been described in benign and malignant infiltrative processes. This raises the question of the relationship between the presence of myofibroblasts and the aggressive behavior of a neoplasm. PMID- 3091798 TI - Botryomycosis of the oral regions. AB - Botryomycosis is an unusual bacterial infection capable of producing chronic granulomatous inflammation and characterised by the production of distinctive grains formed by the interaction of the infective bacteria with the host tissues. The occurrence of this infection in a healthy individual generally results in locally destructive lesions which can clinically mimic a sarcoma. A case is reported involving the oral regions of a healthy adult male which illustrated these features and a discussion is presented of the diagnostic features of this condition. PMID- 3091799 TI - [A study of plasma histaminase activity in the patients with pollinosis]. PMID- 3091800 TI - Androgen resistance in the neonate: use of hormones of hypothalamic-pituitary gonadal axis for diagnosis. PMID- 3091801 TI - Once daily therapy for streptococcal pharyngitis with cefadroxil. AB - To determine if a single daily dose of cefadroxil would be effective in the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis, 196 patients with GABHS pharyngitis were randomly assigned to receive either penicillin V 250 mg three times daily or cefadroxil 30 mg/kg once daily, for 10 days. Outcome was measured by the ability to isolate GABHS from the upper respiratory tract 18 to 24 hours after the onset of therapy, the impact on the clinical course, and the bacteriologic treatment failure rate. There was no significant difference in the number of patients in the cefadroxil and penicillin V treatment groups with throat cultures positive for GABHS at the 18 to 24-hour follow-up visit (0% and 2%, respectively), and the clinical responses of the patients in the two treatment groups were similar. Of the 99 patients in the three times daily penicillin V group, six (6%) had strains of GABHS isolated on one of the follow-up cultures that were identical to the strains isolated from their initial throat cultures and were considered to have bacteriologic treatment failures. Of the 96 patients in the once daily cefadroxil group, two (2%) were considered to have bacteriologic treatment failures. A single daily dose of cefadroxil appears to be as effective in the treatment of GABHS pharyngitis in this population as penicillin V given three times daily. PMID- 3091802 TI - The taxonomy of Sarcocystis (Protozoa, Apicomplexa) species. AB - The taxonomy of the heteroxenous apicomplexan protozoan genus Sarcocystis was reviewed, and a list of 122 species with their synonyms and hosts given. Both definitive and intermediate hosts are known for only 56 species. The fine structure of the sarcocyst wall may change with age and is not considered necessarily satisfactory for separating species. Specificity for the intermediate host is not narrow for all species. Earlier work on transmission of the parasite from one intermediate host to another should be repeated in the light of present knowledge of the life cycle of species of Sarcocystis. PMID- 3091803 TI - Stage and species specificity of antigens encoded by two geographic strains of Schistosoma mansoni mRNA. AB - Proteins translated in vitro from Schistosoma mansoni adult worm mRNA were assessed for their antigenic specificities compared to different stages, strains and species of the parasite. RNA was extracted from both Puerto Rican and Brazilian parasites and directed the synthesis of high molecular weight proteins. Preabsorption of immune human serum with schistosomula was used to determine whether the in vitro translated proteins contained antigens shared between the adult and this immature stage. Three antigens (Mr 36,000, 29,000, 18,000) were observed to be present in both stages. When adult worm mRNA from 2 different geographic strains of S. mansoni (Puerto Rican and Brazilian) were compared, certain antigenic differences were found in their in vitro translation products (proteins at Mr 78,000, 26,000, 24,000, 22,000, 15,500), suggesting that different antigenic pools may exist in nature. The species specificity of the in vitro proteins was assessed using individual sera from humans whose species of schistosome infection and egg counts were known. Immunoprecipitation with these sera demonstrated that a large number of immunologically cross-reactive proteins were shared between S. mansoni and Schistosoma haematobium but not Schistosoma japonicum. Antigens or antigen complexes at Mr 47,000 and 37,000 were detected only in the immunoprecipitations using anti-S. mansoni sera, whereas an antigen of Mr 39,000 was precipitated only by anti-S. haematobium sera. The recognition of any 1 antigen or group of antigens, however, did not distinguish between intensities of infection. PMID- 3091804 TI - Besnoitia strain differentiation using isoenzyme electrophoresis. PMID- 3091805 TI - Unusual variant of familial aniridia. AB - A woman and her two children had apparent dominantly inherited ocular abnormalities including aniridia, ptosis, nystagmus, corneal pannus, persistent pupillary membrane, lenticular opacities, and foveal hypoplasia. A broad spectrum of iris abnormalities was observed: the daughter had aniridia with persistent pupillary membrane strands traversing the anterior lens capsule; the iris of the mother and son had a velvety surface with no detailed crypts, but did have some persistent pupillary membrane tags extending from the collarette. All three family members had moderately severe bilateral ptosis, pendular nystagmus, corneal pannus, and visual acuity of 20/200. Several systemic abnormalities also were noted, including obesity and mental retardation in the two children, and alopecia, cardiac abnormalities, and frequent spontaneous abortion in the mother. Family history indicated that the children's maternal grandmother also had similar ocular findings. We believe that this constellation of findings represents a rare, apparently dominant, variant of aniridia. PMID- 3091806 TI - Colonic obstruction in a child with von Recklinghausen's neurofibromatosis. AB - A child is reported who developed partial colonic obstruction from an intussuscepting polypoid mass in the transverse colon. A 5 cm plexiform ganglioneurofibroma was found at laparotomy. Examination of the entire gastrointestinal tract revealed no other neurogenic tumors. Gastrointestinal involvement by neurofibromatosis in children is rare; however, children with von Recklinghausen's disease who complain of vague abdominal symptoms should be evaluated for gastrointestinal tumors. PMID- 3091808 TI - Mechanisms of gentamicin transport in kidney epithelial cell line (LLC-PK1). AB - The characteristics of gentamicin transport have been studied by using cultured kidney epithelial cell line LLC-PK1. The uptake of gentamicin by the LLC-PK1 cells appeared to be linear for 30 min and reached the equilibrium at day 1. Marked stimulation of gentamicin uptake was observed on the development of a confluent cell density, accompanied by the increases of marker enzyme activities and Na+-dependent D-glucose transport in the apical membranes. Gentamicin uptake was inhibited by metabolic inhibitors such as rotenone and 2,4-dinitrophenol, and was inhibited competitively in the presence of other aminoglycosides. Depending on the external calcium concentration, calcium ionophore A23187 stimulated gentamicin uptake, whereas ethylene glycol bis(beta-aminoethyl ether)N,N1 tetraacetic acid, a calcium chelator, inhibited gentamicin uptake. These results suggest that gentamicin uptake by the LLC-PK1 cells may be mediated via specialized transport system, and calcium ion movement may play an important role as a regulatory factor for this transport system. PMID- 3091807 TI - Drug pharmacokinetics and the carbon dioxide breath test. AB - The interrelationship of the pharmacokinetics of a drug and the expiration of carbon dioxide formed as a metabolite have been studied. The pharmacokinetic characteristics of the drug that affect the usefulness of the carbon dioxide excretion as a measure of liver function were examined by means of computer simulations. The parent drug extraction ratio, fraction demethylated, volume of distribution, and absorption rate of an oral dosage form all contribute to the carbon dioxide breath test result. A drug that would be a useful substrate when the carbon dioxide breath test is used as a probe for changes in liver function should be at least 50% metabolized by demethylation, have a hepatic extraction ratio of 0.2-0.5, and be administered in a form that is rapidly absorbed. PMID- 3091809 TI - p-Hydroxymercuribenzoic acid inhibits arachidonic acid esterification into two distinct pools and stimulates insulin release in intact rat islets. AB - Activation of an islet phospholipase A2 may contribute to glucose-induced insulin release. In order to simulate the accumulation of the resultant hydrolytic products (arachidonic acid, AA; its lipoxygenase-derived oxygenation product 12 hydroxyeicosatetraenoic acid; and lysophospholipids) without many of the other concomitants of beta cell activation, we studied the effects on intact rat islets of p-hydroxymercuribenzoic acid (PHMB), which inhibits the reacylation of lysophospholipids with AA in other cell types. PHMB inhibited in a dose responsive fashion (-90% at 500 microM) the incorporation of [3H]AA into a "basal" pool or pools whose release and reuptake mechanisms appeared to be largely energy- and Ca++-independent (resistant to inhibition by mannoheptulose, antimycin A or CoCl2); reciprocally, islets prelabeled with [3H]AA accumulated an increased amount of [3H]-12-hydroxyeicosatetraenoic acid (twice basal at 200 microM PHMB and three times basal at 500 microM) when reacylation of any [3H]AA released basally at 1.7 mM glucose was inhibited. PHMB also blocked (by up to 99% at 500 microM) the incorporation of [3H]AA into a functionally defined, glucose stimulated compartment of fatty acid (tightly coupled to the islet 12 lipoxygenase) whose release and reuptake required metabolic energy and Ca++. It was also demonstrated that PHMB inhibited the esterification of [3H]AA (at low or high glucose concentrations) into specific phospholipids in islet membranes. In parallel with these alterations in lipid metabolism, PHMB caused rapid, potent and reversible increments in insulin release with a threshold concentration (about 25 microM) identical to that inhibiting AA fluxes. PHMB both initiated release (at 1.7 mM glucose) and potentiated the effects of islet fuels (16.7 mM glucose or 15 mM alpha-ketoisocaproic acid). Thus, pharmacologic manipulation of the AA reuptake mechanism is a new approach to unmask potential roles in insulin release of phospholipid hydrolysis products from different lipid pools and in the absence or presence of phospholipase A2 activation. PMID- 3091810 TI - Evidence against serotonin as a vasoconstrictor neurotransmitter in the rabbit basilar artery. AB - It has been suggested recently that serotonergic nerves distinct from the known adrenergic innervation are present in cerebral blood vessels. We have confirmed that serotonin is present in the wall of rabbit cerebral arteries using a high performance liquid chromatography technique, with levels in the basilar artery of 0.27 +/- 0.04 microgram/g wet wt. Furthermore, adrenergic denervation in vitro with 6-hydroxydopamine, while substantially reducing norepinephrine content, did not alter serotonin levels in the basilar artery. However, it was not possible to demonstrate specific accumulation of [3H]serotonin into distinct serotonergic nerves. Both the basilar artery and ear artery (which has been shown not to be innervated with serotonergic nerves) accumulated [3H]serotonin when incubated with a low concentration (10(-8) M). However, [3H]serotonin accumulation was reduced markedly in 6-hydroxydopamine-treated vessels as well as in the presence of the norepinephrine uptake blocker, desmethylimipramine. Furthermore, pretreatment with the serotonin uptake blocker, fluoxetine, did not inhibit selectively [3H]serotonin accumulation in the basilar artery. Thus, the majority of [3H]serotonin accumulation can be attributed to adrenergic nerves. The possibility that serotonergic nerves contribute to the neurogenic constrictor response of the rabbit basilar artery was also tested. Adrenergic denervation with 6-hydroxydopamine in vitro abolished the constrictor response to transmural nerve stimulation completely, but levels of endogenous serotonin were not affected. Thus, although the presence of endogenous serotonin in cerebral arteries has been confirmed, this substance does not appear to contribute to the neurogenic vasoconstriction seen in this vessel. PMID- 3091811 TI - Effects of hypercapnia and hypoxia on nasal vasculature and airflow resistance in the anaesthetized dog. AB - The experiments were performed on anaesthetized dogs which breathed spontaneously or were artificially ventilated and paralysed. The spontaneous nasal arterial blood flow was measured on one side of the nose while nasal vascular resistance was determined on the other side simultaneously. Nasal arterial blood flow was measured by means of an electromagnetic flow sensor placed around the terminal branch of the internal maxillary artery, the main arterial supply to the nasal mucosa. Nasal vascular resistance was measured by constant-flow perfusion of the terminal branch of the internal maxillary artery. Nasal airway resistance was assessed by monitoring the transnasal pressure at constant airflow through each side of the nose simultaneously. Hypercapnic gas challenge (8% CO2, 30% O2 in N2) to the lungs increased nasal vascular resistance and decreased nasal airway resistance. Similar gas challenge to the nose did not affect nasal vascular resistance but decreased nasal airway resistance. Hypoxic gas challenge (6% O2 in N2) to the lungs did not affect the nasal vascular resistance but decreased nasal airway resistance only when the nasal vascular bed was under controlled perfusion. Similar gas challenge to the nose did not affect either nasal vascular or airway resistance. Arterial chemoreceptor stimulation by intracarotid injection of sodium cyanide increased nasal vascular resistance and decreased nasal airway resistance. The nasal vascular response to hypercapnia and arterial chemoreceptor stimulation was reflex in nature, being abolished by nasal sympathectomy. The nasal airway response to hypercapnia, hypoxia and arterial chemoreceptor stimulation was reflex in nature, being partially or completely abolished by nasal sympathectomy. Hypercapnia probably induced a local vasodilatatory effect on the capacitance vessels whereas hypoxia had no direct action on the vasculature. PMID- 3091813 TI - Coping with the decline in census: balancing the bottom line and quality care. PMID- 3091812 TI - The ionic mechanism of intracellular pH regulation in crayfish muscle fibres. AB - The ionic mechanism of intracellular pH (pHi) regulation was investigated in isolated muscle fibres of the carpopodite adductor in the crayfish Astacus fluviatilis by electrophysiological means with pH, Na+ and Cl- -sensitive liquid ion exchanger micro-electrodes. In eighty-six cells a mean pHi of 7.14 +/- 0.12 (S.D.) at a membrane potential of--79.7 +/- 3.4 mV was found under control conditions which is about one pH unit more alkaline than predicted from passive distribution and indicates the presence of an acid-extrusion mechanism. In order to study pHi recovery the cells were acid loaded by exposure either to NH4 Cl or CO2. The effects of HCO3- and DIDS (an inhibitor of the anion exchange) on pHi recovery as well as the HCO3- -dependent decrease of intracellular Cl- during pHi recovery indicate that in pHi regulation a mechanism of acid extrusion is involved which exchanges extracellular HCO3- for intracellular Cl-. In CO2/HCO3- free solution or in salines with DIDS, pHi recovery was retarded to the same degree, but the effects were not additive. Because of this the remaining pHi recovery must originate from an HCO3- -independent acid-extrusion mechanism. In Na+ -free solution any pHi recovery was blocked; if pHi recovery occurred it was accompanied by an increase of intracellular Na+ activity (aiNa). From these results it was concluded that all acid extrusion mechanisms which contributed to pHi recovery are coupled to an influx of Na+. A Na+/H+/HCO3-/Cl-, and a separate Na+/H+, exchange are proposed as a model of pHi regulation in the crayfish muscle fibre. Similar kinds of acid extrusion mechanisms are found in the neurone of the crayfish (Moody, 1981), with the difference that in the muscle fibre pHi regulation is achieved mainly by the former process. The rate of pHi recovery is considerably lower in the muscle fibre than in the neurone or in the sensory cell (Moser, 1985) of crayfish. PMID- 3091814 TI - Outbreak of meningitis due to Neisseria meningitidis--a microbiological profile. PMID- 3091815 TI - Pre-erythrocytic development and associated host responses to Haemoproteus meleagridis (Haemosporina: Haemoproteidae) in experimentally infected domestic turkeys. AB - Two generations of pre-erythrocytic schizogony occurred in skeletal and cardiac muscle of domestic turkeys infected with sporozoites of Haemoproteus meleagridis. First generation schizonts reached maturity approximately five days post inoculation (DPI) and developed in capillary endothelial cells and myofibroblasts. The schizonts ranged from 12 to 20 microns in diameter and produced long (5-6 microns), slender merozoites. Early second generation schizonts were first detected in capillary endothelial cells between 5 and 8 DPI. They were cylindrical and ranged in size from 5 to 8 microns in diameter and up to 28 microns in length. Second generation schizonts which reached maturity by 17 DPI were surrounded by a thick, hyaline wall and were packed with numerous spherical merozoites less than 1 micron in diameter. Mature megaloschizonts were fusiform, ranged from 30 to 113 microns in diameter, and extended as much as 465 microns along the long axis of muscle fibers. Merozoites developed as buds from cytomeres that formed between 8 and 14 DPI. Infected turkeys developed a moderate to severe myositis within 5 DPI and were lame in one or both legs. The myositis was associated with the necrosis of scattered groups of muscle fibers. Muscle fibers surrounding mature megaloschizonts were swollen and hyaline. Megaloschizonts were surrounded occasionally by fibroblasts and infiltrates of mononuclear cells. The morphology and site of development of mature megaloschizonts of Haemoproteus meleagridis are contrasted with those of other avian haemosporidians. PMID- 3091816 TI - Rumen ciliate fauna of some Brazilian cattle: occurrence of several ciliates new to the rumen, including the cycloposthid Parentodinium africanum. AB - Parentodinium africanum was observed in rumen contents of four Brazilian cattle and constituted 4.4, 0.9, less than 0.1, and 10.0% of the total ciliates. This appears to be the first observation of the family Cycloposthiidae in the rumen habitat. Blepharoconus krugerensis, previously observed in the intestines of the elephant, and an unknown species of ciliate with many characteristics similar to the family Paraisotrichidae were each observed in a single animal. A new subspecies, Diplodinium flabellum laterospinatum n. subsp., is also described. Total number of ciliates per ml of rumen contents ranged from 9.0 to 51.2 X 10(4) and included an overall total of 55 species and 4 subspecies. PMID- 3091817 TI - [Enthesopathy of the upper insertion of the musculus rectus femoris. A retrospective sign of tendon rupture in sports pathology]. AB - We report 4 cases of post-traumatic enthesopathy occurring later after rupture of rectus femoris tendon from the anterior superior iliac spine. Radiographic feature and clinical picture are typical of diagnosis. PMID- 3091818 TI - General practitioner prescribing of total parenteral nutrition at home. AB - An increasing number of patients, returning to the community after major surgical procedures, receive short- or long-term total parenteral nutrition at home. As total parenteral nutrition is initiated by specialist hospital centres patients may find themselves a considerable distance from that centre when they return home. The hospital may therefore relinquish responsibility for funding the supply of parenteral fluid to a more local source.This report describes how total parenteral nutrition can be managed by a general practitioner. PMID- 3091819 TI - Establishment of gradients of riboflavin, L-lysine and alpha-aminoisobutyric acid across the perfused human placenta. AB - The mechanism for establishing transplacental gradients was studied in the dually perfused human placental lobule by recirculating either the maternal or fetal perfusate and leaving the other circuit open. Antipyrine, used as a reference molecule, rapidly reached equivalent concentrations in both perfusates regardless of which was recirculated. In contrast, riboflavin, L-lysine and alpha aminoisobutyric acid showed distinctive kinetics at each surface of the placenta. Recirculation of the maternal perfusate quickly depressed the concentrations of these compounds and maintained them at levels of 50-70% of the fetal concentration. Recirculation of the fetal perfusate was followed by a gradual increase in concentrations, establishing gradients 1.2-1.7 times the maternal. It appears that uptake at the maternal surface greatly exceeds release, whereas the two rates are more nearly balanced at the fetal surface. The net effect is extraction of substrate from the maternal circulation and transfer to the fetal, where it accumulates to form a gradient. PMID- 3091820 TI - Management of phenotypic female patients with an XY karyotype. AB - Nine phenotypic female patients with XY karyotype were evaluated through a clinical, cytogenetic, hormonal, endoscopic and histologic diagnostic protocol. Seven patients complained of primary amenorrhea and two patients of abnormal puberal development. The final diagnosis was XY gonadal dysgenesis (n = 5) and testicular feminization syndrome (n = 4). Two patients were less than 155 cm tall, and the remainder were over 155. Minor somatic anomalies were found in two patients with XY gonadal dysgenesis. Patient with testicular feminization syndrome had FSH and LH within the normal range, and patients with XY gonadal dysgenesis had elevated FSH and LH levels. Gonadoblastomas were found in two patients with XY gonadal dysgenesis (one patient with XO/XX/XY mosaicism). Laparoscopy and gonadal biopsy might be useful in some patients to avoid confusion between XY gonadal dysgenesis and testicular feminization syndrome. Early diagnosis of XY gonadal dysgenesis is always desirable, and bilateral gonadectomy is indicated as soon as the diagnosis is made in patients with a Y chromosome and elevated FSH levels. Surgical removal of the gonads from patients with testicular feminization should be delayed until the completion of puberty because of the low risk of malignancy. PMID- 3091822 TI - Monitoring the impact of the environment on health. PMID- 3091821 TI - Anorectal ulcers as a complication of migraine therapy. PMID- 3091823 TI - Natural methods of family planning. PMID- 3091824 TI - Joint finance and planning using a fresh approach. PMID- 3091825 TI - Hazard Analysis Critical Control Point (HACCP) concept: application to bivalve shellfish purification systems. PMID- 3091826 TI - Mesothelioma in Israel (1973-1982). PMID- 3091827 TI - Health manpower and population change in Nigeria. PMID- 3091829 TI - Development of local food and health policies in Britain. PMID- 3091828 TI - Port health not unlimited. PMID- 3091830 TI - Selective thromboxane synthetase inhibitors. 4. 2-(1H-imidazol-1-ylmethyl) carboxylic acids of benzo[b]furan, benzo[b]thiophene, indole, and naphthalene. AB - The preparation of a series of 2-(1H-imidazol-1-ylmethyl)-substituted carboxylic acids of benzo[b]furan, benzo-[b]thiophene, indole, and naphthalene is described. All compounds showed a similar level of activity as TxA2 synthetase inhibitors in vitro, having IC50 values between 1 and 7 X 10(-8) M. In the cases examined, compounds had, at most, only negligible activity against PGI2 synthetase, cyclooxygenase, and steroid 11 beta-hydroxylase. The benzo[b]thiophenes generally showed the greatest potency in vivo, and compounds 72, 73, and 75 caused almost complete inhibition of thromboxane production for 6 h after oral administration of 0.5 mg/kg to conscious dogs. In the case of 73 and 75, thromboxane production was still inhibited by 80% after 24 h. PMID- 3091831 TI - Synthesis of thyrotropin-releasing hormone analogues. 2. Tripeptides structurally greatly differing from TRH with high central nervous system activity. AB - A new series of thyrotropin-releasing hormone (TRH) analogues, obtained by further modifications of our most potent central nervous system (CNS) stimulating neutral tripeptides at both termini, were synthesized by the pentafluorophenyl ester method and tested for CNS and thyrotropin (TSH) releasing activity. Replacement of pyroglutamic acid by pyro-2-aminoadipic acid, 2-oxoimidazolidine-4 carboxylic acid or gamma-butyrolactone-gamma-carboxylic acid and that of proline by pipecolic acid, thiazolidine-4-carboxylic acid, or homoproline in [Leu2]- and [Nva2]TRH led to tripeptides structurally widely different from TRH. In spite of this fact, 7 of the 17 analogues (1, 2, 8-10, 16, and 17) have stronger anticataleptic effect than TRH, with negligible or no hormonal potency. The highest CNS activity was achieved when pyroglutamic acid was replaced by pyro-2 aminoadipic acid at the N-terminus [pAad-Leu-Pro-NH2, 1 (RGH 2202), and pAad-Nva Pro-NH2,2]. A novel synthesis of L-2-aminoadipic acid suitable for large-scale preparation is also described. PMID- 3091832 TI - Folate analogues. 26. Syntheses and antifolate activity of 10-substituted derivatives of 5,8-dideazafolic acid and of the poly-gamma-glutamyl metabolites of N10-propargyl-5,8-dideazafolic acid (PDDF). AB - The poly-gamma-glutamyl derivatives of n10-propargyl-5,8-dideazafolic acid (PDDF) with a chain length of up to five glutamate residues were synthesized from N10 propargyl-5,8-dideazapteroic acid by the solid-phase procedure. These compounds were evaluated for their antifolate activity using folate-requiring microorganisms and intact and permeabilized L1210 cells and as inhibitors of dihydrofolate reductase and thymidylate synthase derived from L. casei. The polyglutamylated derivatives of PDDF (1) were more active than the parent compound in inhibiting the growth of L. casei, thymidylate synthesis in permeabilized L1210 cells, and L. casei thymidylate synthase. Two analogues of 5,8-dideazafolic acid (2 and 3), one with a 2-butyne and another with a cyclopropylmethyl substituent at N10, were also synthesized and evaluated for their antifolate activities using the above-mentioned test systems. They were considerably less active than PDDF or its polyglutamylated derivatives. N10 Propargyl-5,8-dideazapteroyl tri-, tetra-, and pentaglutamates were equipotent with 5-fluorodeoxyuridylate as inhibitors of thymidylate synthesis in permeabilized L1210 cells. The polyglutamyl metabolites of PDDF were shown to be the most potent antifolate inhibitors of L. casei and L1210 thymidylate synthases yet described. PMID- 3091833 TI - Mitomycin C analogues with increased metal complexing ability. AB - Twenty-three new mitomycin C analogues designed to have increased metal complexing ability were synthesized and tested against P388 leukemia in mice. Their ability to complex Cu(II) was revealed by the shifts in their UV absorption spectra caused by this metal. One analogue was clearly more active than mitomycin C in the antitumor assay and two others had good activity. Correlation between antitumor activity and Cu(II) complexing ability was ambiguous. The most active compounds were either not complexers or they were complexers limited to the 2-(2 pyridyl)alkyl type substituent on N7. A variety of amino acid substituents on N7 showed only weak antitumor activity. PMID- 3091834 TI - Synthesis and antifolate properties of 5,10-methylenetetrahydro-8,10 dideazaminopterin. AB - The synthesis of the 5,10-methylene analogue of 5,6,7,8-tetrahydro-8,10 dideazaminopterin, a potential dual inhibitor of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) enzymes, is described. The dimethyl ester of 10 carboxy-4-amino-4-deoxy-8,10-dideazapteroic acid was converted to the tetrahydro derivative by hydrogenation. Thermally induced cyclization of the 10-carbomethoxy and the 5-NH groups afforded the 5,10-carbonyl analogue. Reduction of the lactam with borane readily yielded the key 5,10-methylene-4-amino-4-deoxy-8,10 dideazatetrahydropteroic acid methyl ester. Saponification of the benzoate ester and coupling with L-glutamate concluded the synthesis. The title compound was a modest inhibitor of growth in folate-dependent bacteria. Streptococcus faecium and Lactobacillus casei, but inhibition of DHFR or TS derived from L. casei was poor. The compound was also a weak inhibitor of DHFR derived from L1210 murine leukemia and was a weak inhibitor of L1210 growth in culture. PMID- 3091835 TI - Inhibitors of human purine nucleoside phosphorylase. Synthesis, purine nucleoside phosphorylase inhibition, and T-cell cytotoxicity of 2,5-diaminothiazolo[5,4 d]pyrimidin-7(6H)-one and 2,5-diaminothiazolo[4,5-d]pyrimidin-7(6H)-one. Two thio isosteres of 8-aminoguanine. AB - 8-Aminoguanine is a potent inhibitor of purine nucleoside phosphorylase (PNP) and also a substrate of PNP. Two thio isosteres of 8-aminoguanine, 2,5 diaminothiazolo[5,4-d]pyrimidin-7(6H)-one (2) and 2,4-diaminothiazolo[4,5 d]pyrimidin-7(6H)-one (3), which cannot be substrates of PNP, were synthesized and evaluated for their inhibitory activity against PNP. They were found to be weak inhibitors of PNP and to be noncytotoxic for MOLT-4 T-cells in culture. PMID- 3091836 TI - Differentiation of heterozygotes in recessive albinism. AB - Skin pigmentation was measured by reflectance spectrophotometry in 43 albinos, 44 of their relatives, and 123 random controls among Swazi subjects in southern Africa. Mean reflectance of the subject groups diminishes in the sequence affected subjects, obligate heterozygotes, other unaffected family members, random subjects, and the differences among the unaffected groups are highly significant. A discriminant function fitted to the obligate heterozygotes and random subjects is significant statistically but is not efficient enough to be applied in the diagnosis of the non-carrier state. PMID- 3091837 TI - Drug resistance patterns and susceptibility to aflatoxin B1 of strains of Escherichia coli and Staphylococcus aureus. AB - The antibacterial properties of aflatoxin B1 have been evaluated against antibiotic-resistant clinical isolates of Escherichia coli and Staphylococcus aureus. The inhibition of growth ranged from 11.5 to 60.0% and 4.5 to 18.5% in the strains of S. aureus and E. coli, depending on the extent of drug resistance. Aflatoxin-B1 binding varied with toxin concentration, the presence of surfactants (Tween-80 or EDTA) as well as with the antibiotic-resistance pattern; binding was maximal in antibiotic-sensitive strains and least in the most resistant strains. Binding of aflatoxin B1, correlated with growth inhibition. Aflatoxin B1 also caused leakage of cell contents and decrease in inulin uptake, effects which were also concentration dependent. PMID- 3091838 TI - Continuous measurement of calcium influx in mammalian nonmyelinated nerve fibers: effects of Nao, Cao, and electrical activity. AB - A new technique for continuous monitoring of the cellular calcium was developed and used for studying the effects of external and internal Na (Nao and Nai), external Ca (Cao), Ca ionophore A23187, and electrical activity on membrane-bound and intracellular Ca in mammalian nonmyelinated nerve fibers. Increasing Cao increased both the membrane-bound and the intracellular Ca. Lowering Nao increased the membrane-bound fraction of Ca indicating that lack of Nao enhanced the capacity of the plasma membrane to bind Ca, and produced an increase of the internal Ca pool. Increasing Nai by treatment with ouabain enhanced the Ca inflow in both, the presence and absence of Nao, presumably by stimulating the Cao/Nai exchange. The Ca ionophore A23187 produced a large and irreversible increase in the intracellular Ca without affecting the membrane-bound fraction. On the other hand, electrical activity, which is known to produce a large increase of the total Ca in squid axon, had no measurable effect on the total calcium content in our preparation. It is concluded that in mammalian nerve fibers a Ca load by exposition to Na-free solution or to A23187 produces an accumulation of Ca into the intracellular Ca stores, whereas during electrical activity the membrane associated extrusion mechanisms are able to maintain the intracellular Ca2+ below the threshold for intracellular sequestration. Furthermore, the results indicate that the intracellular sequestration mechanisms are dependent on the internal concentration of Na. PMID- 3091839 TI - Sodium flux in the apical membrane of the toad skin: aspects of its regulation and the importance of the ionic strength of the outer solution upon the reversibility of amiloride inhibition. AB - Injection of small pulses of concentrate solutions of salts or drugs into the outer bathing fluid led to sudden increases of its solute concentration. Vigorous stirring of the outer bathing solution was used to minimize the thickness of the unstirred layer adjacent to the outer skin surface. Pulses of 1 M NaCl injected into the outer compartment induced sharp increases of the SCC following a time course variable with the magnitude of the pulse and the particular condition of each skin. Comparison of the spontaneous decline of the SCC with the decline induced by a small dose of amiloride, where an increase in R was observed, indicates that the spontaneous decline cannot be explained simply as a reduction of the Na permeability of the apical membrane by self-inhibition of feedback inhibition of the apical membrane Na channels. Reduction of the driving force for Na movement into the epithelial cells must play an important role in the process. Reversibility of the amiloride inhibition of the SCC was highly dependent upon the ionic strength of the solution used to rinse and wash out the inhibitor from the outer skin surface. With H2O, the amiloride molecules washed out slowly as compared to NaCl or KCl solutions. Na or K have the same ability to dislodge the amiloride molecules from their binding sites. This effect is apparently of a purely electrostatic nature. PMID- 3091840 TI - A study of the effects of substrates on intracellular pH in toad ventricular strips. AB - The ability of different substrates to affect myocardial function is well established but the mechanism for this effect has yet to be determined. To explore this area further, the studies described below were designed to determine the effect of different metabolic substrates, glucose or pyruvate, on myocardial response to hypercapnia. To assess this response, both the mechanical performance and the intracellular pH (pHi) were continuously measured. Intracellular pH was measured using the changes in absorbance of the vital staining dye, neutral red (NR). Although the presence of either substrate did not affect the response to hypercapnia, the addition of pyruvate was accompanied by a significant change in pHi. Specifically, there was a monotonic decrease in pHi comparable to that observed when PCO2 is increased from 5% to 10% (delta OD = -0.018 +/- 0.002 CO2; delta OD = -0.020 +/- 0.002 PYR, respectively). The mechanical response was similar for both; developed tension (tau) decreased initially (97 +/- 6% v. 93 +/ 8%) and then recovered (115 +/- 4% v. 101% +/- 5%). However, the changes in the maximum rate of relaxation, i.e. minimum time derivative: (tau mn) were dependent on the cause of the decrease in pHi. With hypercapnia, tau mn initially decreased and this was followed by a recovery phase which was 147 +/- 8% of the initial value. With pyruvate, tau mn decreased to 81 +/- 5% of control and was followed by no recovery. Because of the difference in the changes in tau mn, the effects of theophylline [3, 5] on these responses were determined. There was no effect on the response to an increase in PCO2. However, with theophylline present, the addition of pyruvate was accompanied by an increase in pHi (delta OD = + 0.005 +/ 0.001). The mechanical response was consistent with this increase and was similar to that seen when PCO2 is decreased from 10% to 5%. Specifically, there was an increase in tau (122 +/- 7%) followed by a small decrease (113 +/- 4%). Tissue assays for lactate showed a significant increase with the introduction of pyruvate. However, this increase was not affected by the presence of theophylline despite the opposite response of pHi. The data suggest that pyruvate affects myocardial function by altering pHi, and this effect is not due to an increase in lactate. In addition, the data are consistent with the model that the heart is capable of accommodating changes in pHi with only transient effects on contractile function. PMID- 3091841 TI - The template properties of some oligodeoxynucleotides containing cytidine and guanosine. AB - The co-condensation of guanosine- and cytidine-5'-phospho-2-methylimidazolide on various oligodeoxynucleotides containing C and G has been studied. We find that GC7 is an effective template for the incorporation of C into products of the form GnC, whereas C7G does not act as a template for C incorporation. The template C3GC3GC3GC3 directs the synthesis of complementary products, but the yield of long oligomers is very small. Templates in which G residues are contiguous or separated by a single C residue are ineffective, while templates containing the sequence GCCG are very inefficient. The significance of these findings in the context of prebiotic chemistry is discussed. PMID- 3091842 TI - Synthesis of hydrocarbons under presumed prebiotic conditions using high frequency discharge. AB - Various hydrocarbons were synthesized by high-frequency discharge in a primordial terrestrial model atmosphere. The products were extracted by benzene or methanol and analyzed by GC-MS. The mean carbon chain length of the hydrocarbons formed by the discharge through pure CH4 gas was less than 6. Benzene was also obtained. Some isomers were obtained for each of the hydrocarbons containing a given number of carbons. When a small amount of C2H2 was added to the CH4, longer chain compounds were formed, as compared with discharge in CH4 only. However, when the amount of C2H2 was increased, unextractable high molecular weight compounds were produced. The amounts of products decreased as the mixing ratio of CO2 to CH4 increased. No hydrocarbons were detected when the ratio of CO2/CH4 exceeded 1. PMID- 3091843 TI - Self-organization in prebiological systems: simulations of a model for the origin of genetic information. AB - Computer simulations of a "spin glass" model for the origin of biological information are discussed. Selection is found to occur among a wide diversity of possible species, and in addition competition, adaptation, and hysteresis are all exhibited. PMID- 3091844 TI - The use of genetic complementation in the study of eukaryotic macromolecular evolution: rate of spontaneous gene duplication at two loci of Drosophila melanogaster. AB - Gene duplications must play an important role in the evolutionary development of living organisms. Presented here is a general scheme that uses complementary alleles to isolate gene duplications in diploid organisms. The technique was used in Drosophila melanogaster to assess the rate of spontaneous gene duplication at two loci, maroon-like and rosy. The results indicate that the rate of duplication of the maroon-like locus is on the order of 2.7 X 10(-6); that the rate of duplication of the rosy locus is approximately 1.7 X 10(-4); and that duplication occurs in males, suggesting that there may actually be two modes of gene duplication in Drosophila melanogaster. PMID- 3091845 TI - How reliable is amino acid sequence homology in predicting similarity of structure and function of c-myc and Ad12 E1A oncogenic proteins? AB - Adenovirus E1A and c-myc genes are known to be capable of transforming primary rat cells when they occur in combination with either polyoma middle-T or T24 Harvey-ras1 genes. There was a low level of amino acid sequence homology between the nuclear adenovirus-12 (Ad12)E1A protein product (289 amino acids) and the c myc protein based on optimal alignment and percentage identity. In contrast to others [Ralston R, Bishop JM (1983) Nature 306:803-806], we concluded that this low level of amino acid sequence homology was not significant, since rabies glycoprotein (RGP), which has no transforming function and localizes to the cell surface, had a similar low level of amino acid sequence homology to the c-myc protein. Furthermore, dot-matrix analysis, when used to test the overall level of amino acid sequence homology, showed no significant homology between c-myc and Ad12E1A, E1B, or RGP. Thus, low levels of amino acid sequence homology between two proteins may not be sufficient to predict structural and functional similarities between them reliably, even if the two proteins appear to share a common function. PMID- 3091846 TI - An apparent progressive and recurrent evolutionary restriction in tissue expression of a gene, the lactate dehydrogenase-C gene, within a family of bony fish (Salmoniformes: Umbridae) AB - Unexpectedly large differences in the tissue patterns of lactate dehydrogenase-C (Ldh-C) gene regulation were observed among species of fish within the family Umbridae (Salmoniformes). Normally, all the species within a family or order of advanced fishes exhibit the same, tissue-restricted pattern of L-lactate dehydrogenase C4 isozyme synthesis--either eye- or liver-restricted expression, but not both. However, within the Umbridae the more anciently derived species had a more generalized (primitive) tissue expression, whereas the more recently derived species had a more tissue-restricted expression, predominating in the eye. Given the relative divergence times among the species estimated by genetic distance (using 51 protein-coding loci), divergence from the presumed primitive expression of the Ldh-C gene appears to have been proceeding more rapidly in some species lineages than others. This narrowing of Ldh-C gene tissue regulatory specificity within the family Umbridae is similar to the general trend observed over much greater evolutionary times within the class of bony fishes. The results support the hypothesis of repeated evolutionary canalizations of Ldh-C gene regulation from the generalized tissue expression in more primitive species to a predictable tissue-restricted expression (in either eye or liver) in advanced species. Furthermore, in the Umbridae, this progressive restriction of tissue expression of isozymes has taken place during the evolution of both the Ldh-C and Ldh-B genes. These evolutionary trends in the regulation of isozyme-locus tissue expression in the bony fishes are consistent with either an intrinsically conditioned trend of change in gene regulation or with a response to natural selection. PMID- 3091847 TI - Neurogenic pulmonary edema. AB - Neurogenic pulmonary edema, although not frequently seen, is extremely important in the differential diagnosis of pulmonary edema. Often the diagnosis is suggested by roentgenogram and clinical history and effective therapy can therefore be instituted. PMID- 3091848 TI - A biomolecular approach to the study of the expression of specific genes in the retina. AB - The central nervous system contains a number of populations of neurons that are morphologically and functionally distinct. To study the genes responsible for the development and maintenance of proteins with unique structural and biochemical properties, polyspecific antisera were produced against normal mouse retinal proteins and used in combination with the rd (retinal degeneration) neurological mutant of the mouse to immunologically identify specific retinal proteins. Western transfer analysis of the proteins present in normal and in mutant retinas identified three classes of neural proteins: those found only in normal retina; those found in normal and in photoreceptorless retinas but not in other tissues; and those found in both normal and mutant retinas, as well as in brain, but not elsewhere. Some of these class 1 proteins were shown to be present in the retinas of other species, including humans, suggesting their importance in the process of vision. The poly A+ RNA was isolated from the retinas of normal mice and used to generate a cDNA expression library in lambda gt-11. This library was screened with polyspecific antisera absorbed with the proteins present in mutant retina, and a number of immunologically positive plaques were cloned. Four of these were shown to code for rhodopsin, the major visual protein in mammalian retinas. The approach described is applicable to other systems in order to generate specific immunological and recombinant DNA probes for examining the expression of specific genes during development and differentiation. PMID- 3091849 TI - Perfusion and superfusion fixation effects on rat mesentery microvascular beds. Intravital and electron microscope analyses. AB - The effects of glutaraldehyde on dimensions and ultrastructure of microvascular beds in rat mesentery were studied in two kinds of experiment, administering the fixative by intra-arterial perfusion at a pressure of 80 mm Hg and by superfusion of the exteriorized mesenteric membrane. The microvascular segments were observed by means of intravital microscopy and recorded on videotape before, during, and after glutaraldehyde reached the microvascular segment being observed. Vascular outer diameters were measured at exactly the same points before and after fixation; in Epon embedded whole-mounts; and in sections analyzed by light and transmission electron microscopy, confirming positively the various segments of the microvascular bed and yielding information concerning the preservation of cellular components. Both experiments confirmed that neither perfusion nor superfusion of glutaraldehyde changes the outer diameter of any segment of the microvascular bed compared to the dimensions 5-10 sec before the blood vessels are reached by the fixative. They remain unaltered also after embedding in epoxy resin. During superfusion, there is a 20-50 sec delay until the blood flow comes to a complete stop. This delay is assumed to give rise to the recorded small undulations of luminal endothelial cell membranes and slight buckling of the entire endothelial layer, probably due to a gradual fall in intravascular pressure. Occasionally, the ultrastructure of some endothelial cells is less well preserved after superfusion fixation. This study demonstrates that intraarterial perfusion of glutaraldehyde renders an instantaneous fixation of mesenteric microvessels, preserving the prefixation dimensions of the various segments and the ultrastructure of the cells. Superfusion of glutaraldehyde is slower in reaching the microvessels and may change slightly the appearance of the vascular wall, and cause some impairment of microvascular functions, such as increased postcapillary leukocyte margination and extravasation. PMID- 3091850 TI - The technique of heterotopic heart-lung transplantation in the rat. PMID- 3091851 TI - Effect of injection of TRH into cerebral ventricles on the analgesic effect of acupuncture and morphine in rats. PMID- 3091852 TI - Schistosomal colonic polyposis: clinical, radiological and parasitological study. AB - One hundred and eight male Egyptian farmers with schistosomal colonic polyposis were reviewed. All patients gave a history of bloody diarrhoea. Sixty-one patients presented with finger clubbing, and four of these patients had painful, tender and swollen wrist, knee and ankle joints. X-ray revealed new bone formation in the bones around these joints. The clinical condition improved with antischistosomal treatment, but the bony changes persisted. Twenty patients showed signs of dependent oedema or ascites. Thirty-one patients had a liver of 8 cm or more below costal margin and 19 patients had a spleen of 8 cm or more below costal margin, a situation not unlike patients with schistosomiasis without polyposis. Fifteen patients had tender abdominal masses in the left iliac fossa which were shown by barium enemas to be clusters of polyps. Anti-schistosomal therapy relieved the obstruction but narrowing persisted in 70% of patients followed up. Severity of schistosomal colonic polyposis correlated with the anatomical distribution of the polyps, with their number and with the egg excretion rates. PMID- 3091853 TI - Oxamniquine treatment for schistosomal polyposis: a 1-2 year follow-up study. AB - A follow-up was carried out into the study of schistosomal colonic polyposis reported in the last article. Eighteen patients with schistosomal colonic polyposis were treated with oxamniquine and their progress was evaluated for 2-3 weeks after treatment, at 3 months and at 12-24 months. Sigmoidoscopy to examine mucosa on the polyps and barium enemata to determine the size and number of polyps showed variable success, but treatment with oxamniquine produced no untoward side effects. PMID- 3091856 TI - Payment by nonsmokers for smoking-related illness. PMID- 3091855 TI - Mural degeneration in the glutaraldehyde-tanned umbilical vein graft: incidence and implications. AB - After discovering an aneurysm in a glutaraldehyde-tanned umbilical vein (GTUV) graft that resulted in graft thrombosis, we reevaluated all patients from our institution who had GTUV grafts implanted for more than 2 years. Of 60 patients identified, 14 of 15 patients with patent grafts were recalled and had either digital subtraction or standard angiographic studies. Angiographic changes in the grafts were graded on a scale of 0 to 3, from normal (grade 0) to frank aneurysmal degeneration (grade 3). Eight grafts (57%) had frank aneurysmal (grade 3) changes, and three other grafts (21%) had preaneurysmal (grade 2) changes. Only one graft was angiographically normal. GTUV grafts undergo aneurysmal degeneration in a significant percentage of implants. Symptomatic aneurysms have presented with thrombosis and limb-threatening ischemia as well as rupture. GTUV aneurysms should be treated by complete graft resection, as segmental resection of diseased portions of grafts resulted in metachronous aneurysm recurrence. Because of the high incidence of GTUV degeneration, the clinical indications for the use of GTUV grafts should be seriously reevaluated, and we recommend that all patients with patent GTUV grafts for more than 2 years be evaluated for the presence of aneurysmal degeneration. PMID- 3091854 TI - Tumor progression in murine leukemia virus-induced T-cell lymphomas: monitoring clonal selections with viral and cellular probes. AB - Clonal selections occurring during the progression of Moloney murine leukemia virus (MuLV)-induced T-cell lymphomas in mice were examined in primary and transplanted tumors by monitoring various molecular markers: proviral integration patterns, MuLV insertions near c-myc and pim-1, and rearrangements of the immunoglobulin heavy chain and beta-chain T-cell receptor genes. The results were as follows. Moloney MuLV frequently induced oligoclonal tumors with proviral insertions near c-myc or pim-1 in the independent clones. Moloney MuLV acted as a highly efficient insertional mutagen, able to activate different (putative) oncogenes in one cell lineage. Clonal selections during tumor progression were frequently marked by the acquisition of new proviral integrations. Independent tumor cell clones exhibited a homing preference upon transplantation in syngeneic hosts and were differently affected by the route of transplantation. PMID- 3091857 TI - Cost-effectiveness of nicotine gum as an adjunct to physician's advice against cigarette smoking. AB - A nicotine chewing gum has recently become available for use as an aid in giving up cigarette smoking. Although its efficacy has been demonstrated in clinic-based smoking cessation programs, its value in a primary care setting is uncertain. We examined the cost-effectiveness of nicotine gum as an adjunct to physician's advice and counseling against smoking during routine office visits. Our findings indicate that the cost per year of life saved with this intervention ranges from $4113 to $6465 for men and from $6880 to $9473 for women, depending on age. This compares favorably with other widely accepted medical practices, eg, treatment of hypertension or hyperlipidemia. Our study, therefore, suggests that nicotine gum is a cost-effective adjunct to physician's advice against cigarette smoking in a primary care setting. PMID- 3091859 TI - Total parenteral nutrition-related cholestasis in infants. AB - An epidemiological study was conducted to estimate the proportion of infants on total parenteral nutrition (TPN) who developed cholestasis and to identify risk factors associated with the development of this disease. Data were abstracted from medical records of 624 infants less than or equal to 30 days of age who were treated with TPN. A case of TPN-related cholestasis was defined as an infant whose serum level of direct bilirubin was greater than or equal to 1.5 mg/dl subsequent to initiation of TPN. Risk factors were assessed using multiple logistic regression analysis. Forty-six of 624 infants in the cohort (7.4%) were classified as having TPN-related cholestasis. The multivariable analysis indicated that cholestasis was associated with intracranial hemorrhage, patent ductus arteriosus, sepsis and gastrointestinal conditions that require surgery. Two distinct processes appear to have occurred: in infants who experienced patent ductus arteriosus or intracranial hemorrhage (conditions associated with hypoxia) where TPN may be the necessary trigger for the development of cholestasis, and in infants with gastrointestinal conditions requiring surgery or sepsis, where cholestasis may develop with or without parenteral infusions. PMID- 3091858 TI - Jonathan E. Rhoads lecture. Intravenous hyperalimentation and cancer. A historical perspective. PMID- 3091860 TI - Fibronectin levels in stressed and septic patients fed with total parenteral nutrition. AB - Plasma fibronectin concentrations were measured in healthy persons as well as in septic and stressed patients. A decrease in plasma fibronectin concentration was shown in volunteers receiving a low energy (600 kcal), amino acids- and lipid deficient diet. Increased fibronectin levels were measured in stressed and septic patients, not receiving enteral nutrition, after adequate total parenteral nutrition (TPN during 1 week). It is concluded that total parenteral nutrition facilitates improved fibronectin synthesis in stressed and septic patients. Total parenteral nutrition containing an amino acid mixture rich in branched amino acids (50.2% BCAA) is not superior to TPN containing a standard amino acid mixture (15.6% BCAA) in this respect. PMID- 3091861 TI - Urea nitrogen excretion in chair-adapted primates. AB - To evaluate the temporal pattern of urea excretion in chair-adapted primates (Macaque fascicularis) on continuous total parenteral nutrition (TPN), two groups of five animals were studied. Group I received continuous TPN (75 glucose kcal; 0.56 g nitrogen; and 100 ml fluid per kg per day) while Group II received a single morning isonitrogenous oral meal along with a continuous isovolemic intravenous infusion of 0.45% saline. Urine was collected hourly in group I for 2 days and every 4 hr in group II for 5 days and analyzed for urea content. Time series analysis revealed no periodicity of urea excretion in either group. Six animals were then studied for a total of 46 TPN days to define the relationship between the urea content of a single 3-hr morning urine aliquot and its respective content in a 24-hr collection. A significant linear relationship was found (r = +0.76, p less than 0.01). However, using this relationship, a reasonable estimate (+20%) of measured 24-hr urea output was achieved only 50% of the time using a single 3-hr urea output. Chair-adapted primates maintained on continuous TPN or a single oral meal with continuous saline infusion do not exhibit a periodic pattern of urea excretion. The variability in 3-hr urinary urea output in the chaired primate on continuous TPN does not consistently permit accurate estimation of the coincident 24-hr urinary urea output. PMID- 3091862 TI - Effects of pH, temperature, concentration, and time on particle counts in lipid containing total parenteral nutrition admixtures. AB - It has been standard practice in the United States to separate lipid emulsion from the other components of total parenteral nutrition (TPN) due to the reported instability of admixed intravenous lipid emulsions. Some clinicians, however, have combined all TPN components into one container and administered these admixtures to patients without apparent difficulties. Infusion of all nutrients from one container has many advantages. In this study standard and concentrated admixtures were aseptically prepared using generally accepted guidelines of the nutritional requirements for a 70-kg patient. Treatments of standard and concentrated admixtures consisted of: storing at 4 degrees C without adjusting the pH; increasing the pH to 6.6 and storing at 4 degrees C; increasing the pH to 6.6 and storing at room temperature. Samples were monitored for 3 weeks by means of Coulter Counter analysis, pH determinations, and visual observations. The pH of the admixtures did not change over 3 weeks. Mean counts of particles with sizes between 1.6 and 25.4 mu increased over time for each treatment group. Within treatments, concentrated admixtures had significantly greater particle counts than the corresponding standard admixtures. Within the standard and within the concentrated admixtures, the particle counts were significantly greater for group one than for group three. Particle counts in group two tended to lie between the values of group one and three. Visual signs of emulsion deterioration were greatest in those admixtures in which the pH was not adjusted and occurred earlier in concentrated admixtures. PMID- 3091863 TI - Decrease of available vitamin A in parenteral nutrition solutions. AB - The efficiency of vitamin A delivery in total parenteral nutrition solutions was determined using spectrofluorometric and radioisotope assays. Experiments incubating total parenteral nutrition solutions in intravenous tubing demonstrated that an 88% decrease in vitamin A content from solution occurred over a 5-hr period. This decrease was independent of the method of assay and was not due to photodecomposition. Recovery of vitamin A from hexane rinses of the intravenous tubing demonstrated that the vitamin decrease was due to uptake by the tubing. Experiments simulating clinical practice situations showed saturation of these binding sites, with mean decrease of 26 to 67% of the vitamin, which were partially dependent on flow-rate. Clinical samples analyzed for comparison showed a greater loss of vitamin (77-98%) from the intravenous solutions. A decrease of vitamin A from solution should be a consideration when using parenteral nutrition. PMID- 3091864 TI - Effects of nutrition on plasma, liver and muscle amino acids in scalded rats. AB - This study set out to investigate the effect of three different parenterally administered diets on the free amino acid (AA) levels in the plasma, muscle, and liver of scalded rats. Diet I consisted of AA (1.4 g/100 g weight) and a high glucose dose (6 g/100 g weight), diet II consisted of AA and a low glucose dose (1.4 g/100 g weight) and in diet III only a low glucose dose was infused. Parenteral nutrition was started on the 3rd day posttraumatically. Sampling was performed on the 7th day posttraumatically. Nitrogen balances were significantly different in all three groups, being lowest in group III. Scalded rats fed isonitrogenously, but with different amounts of glucose showed only minor changes in AA concentrations. However scalded rats fed with a nitrogen-free diet exhibited significantly reduced total muscle and liver AA levels. These decreased AA levels were due to a drop of glycine in the muscle tissue (74%) and liver (49%). Contrary to the clinical catabolic situation in scalded and starved rats, it was not intracellular glutamine but glycine which was considerably influenced by catabolism and starvation. PMID- 3091865 TI - Total parenteral nutrition by a nutrition support team: improved quality of care. AB - Most of the studies that have examined the effect of nutrition support teams (NST) on the quality of total parenteral nutrition (TPN) have found reductions in the frequency of metabolic and central venous catheter related complications. Previous studies have not examined the patterns of nutrient delivery (eg, calories and protein) when TPN is provided either by a primary physician or by a NST. We compared the quality of TPN care provided by our NST or by primary physicians utilizing nonspecialized hospital personnel and resources. As expected, catheter complications were significantly less frequent in NST patients. Assessment of nutritional status and nutrient requirements as well as nitrogen balance were performed and documented significantly more often in NST patients. In addition, nutritional goals for calories and protein were achieved and positive nitrogen balance documented more often in NST patients. The need to consult the NST physician to utilize the NST was not well received by primary attending and resident physicians and resulted in nonuse of the team. In the future, modification of NST policies will be explored to encourage greater utilization of the NST without compromising the high standard of nutrition care delivered by the NST. PMID- 3091866 TI - Effects of total parenteral nutrition on the development of intestinal endotoxemia in rats: a comparison between glucose and lipid. AB - The effects of parenteral nutrition (PN) and of the difference in the PN regimens between glucose and lipid emulsion on the development of endogenous endotoxemia were studied in 40 Wister rats. Endotoxemia was induced by occluding the superior mesenteric vein (SMV) for 30 min. The plasma endotoxin in the portal blood at the time of the release of the SMV occlusion and that in the arterial blood 10 min after the release were quantified. Twenty of the 40 rats had received PN for 48 hr prior to the SMV occlusion. Ten of these 20 rats received the total nonprotein calorie (TNPC) solely with glucose, and the other 10 rats received 25% of the TNPC with lipid emulsion. Ten rats had been allowed free access to lab food until the SMV occlusion. The remaining 10 rats underwent neither the SMV occlusion nor PN, and served as the control group. Both the portal and the arterial endotoxin increased after the release of the SMV occlusion, however the portal endotoxin was higher than that of the arterial one. Both the portal and the arterial endotoxin of the rats supported by PN were significantly lower than those of the rats nourished by lab food, while they were higher than the control values. The difference in the PN regimens did not cause any alteration in the endotoxin levels. These results indicate that the development of intestinal endotoxemia was not influenced by the difference in the PN regimens, but it was rather influenced by a presence of intestinal content. PMID- 3091867 TI - A review of the current national status of home parenteral and enteral nutrition from the provider and consumer perspective. AB - Home parenteral and enteral nutrition (HPEN) has grown rapidly in the past decade. By examining data from physician reports, patient surveys, and the infusion industry, this review attempts to delineate the diagnostic indications, age range, mortality, medical complications and rehabilitation potential of HPEN patients. A clear trend exists towards greater use of this expensive therapy in bowel obstructed cancer patients and in pediatric and geriatric age groups. Complications in parenterally fed patients appear to result in a readmission to the hospital, on average, once every 2 yr. Life expectancy depends heavily on the underlying diagnosis: whereas 50% of the patients with a malignancy survive only 6 months, 50% without a malignancy survive beyond 3 yr. Fifty to 60% of HPEN patients are able to work full time or part time, 15 to 20% are retired or of preschool age, and 20 to 30% are unable to work. The home care service options considered most important by patients are the pharmacy premixing of intravenous solutions, home delivery of supplies by the home service carrier, reimbursement management by the home care service and the availability of a nurse for an initial home visit and 24-hr emergency backup. In regard to fiscal concerns one of the difficult issues that should be addressed is the separation of medical coverage from disability status; another is that enteral feedings can sometimes be a less expensive alternative to parenteral feedings but little information exists about the complications and outcome with this modality and its fiscal reimbursement is much less assured. PMID- 3091869 TI - Prevention of septic complications associated with TPN. PMID- 3091868 TI - The role of protein in nutrition, with particular reference to the composition and use of enteral feeding formulas. A consensus report. AB - In its proposed classification scheme for reimbursement for enteral feeding formulas, the United States Health Care Financing Administration (HCFA) has neglected to consider the importance of making available formulas of varying protein content. In responding to HCFA's proposal, this consensus report reviews information currently available regarding different protein requirements in healthy, ill, and undernourished adults and elderly individuals. HCFA's reimbursement guidelines should reflect sound medical and nutritional practice rather than influencing it adversely, which its original proposal could do. Clinicians should have at their disposal enteral feeding formulas of varying protein/calorie ratios, especially since the following groups often have higher than average protein requirements relative to calorie requirements: the elderly, individuals with physiologic stress such as infection and injury, and patients with protein-calorie undernutrition. PMID- 3091870 TI - Leakage of feedings and gastric contents through ostomy sites. PMID- 3091871 TI - Cutaneous leishmaniasis in Baluchistan: reservoir host and sandfly vector in Uthal, Lasbella. PMID- 3091872 TI - Bioassay for prostaglandin-like activity of garlic extract using isolated rat fundus strip and rat colon preparation. PMID- 3091873 TI - Food hygiene with reference to public health microbiological contaminants of different foods in Rawalpindi and Islamabad. PMID- 3091874 TI - Lipoma of corpus callosum diagnosed by CT scanning--a case report. PMID- 3091875 TI - Radionuclide imaging. PMID- 3091876 TI - Volume-pressure relations of the human pulmonary "venous" system studied by radionuclide angiocardiography and passive leg elevation, with special reference to the effect of nitroglycerin. AB - In an attempt to clarify the effect of nitroglycerin (NTG) on the human pulmonary "venous" (P"V") system, short segments of volume-pressure (V-P) curves in the P"V" system were estimated in 50 patients before and after the sublingual administration of NTG. The pulmonary "venous" volume (P"V"V) was estimated with our own method, using radionuclide (RN) angiocardiography. The mean pulmonary artery wedge pressure (PAW) was measured using a Swan-Ganz catheter. The increments of P"V"V and PAW that occurred during passive elevation of the legs were clues to the estimation of V-P "curves" in this system before and after NTG. In order to calculate a short segment of a V-P curve, the P"V"V was plotted on the ordinate and the PAW on the abscissa. In addition, we presented the effective unstressed volume graphically by extrapolating each short segment of V-P curves towards the volume axis (ordinate). We obtained the following results from the present study; The sublingual administration of NTG caused the P"V"V-PAW-plots to shift to the left (-5.2 +/- 3.6 mmHg, mean +/- SD) and downwards (-19 +/- 11 ml, mean +/- SD). The V-P curves appeared to shift to the left and become steeper after NTG. The average slope (delta V/delta P) was steeper after NTG (19.2 +/- 11.3 ml/mmHg, mean +/- SD) than before NTG (12.4 +/- 7.9 ml/mmHg). The graphically-obtained effective unstressed volume was unchanged with NTG, at least within the operating range of PAW. It is highly probable that NTG causes the tone of the P"V" system to be decreased by way of a relaxation of the vascular beds of the P"V" system. PMID- 3091877 TI - [Permissible degree of hemodilution without impairment of CO2 excretion; anemia and a-ADCO2]. PMID- 3091879 TI - [Automatic respiratory control using expiratory carbon dioxide as partial pressure as an index]. PMID- 3091878 TI - [The effects of dantrolene on the respiratory function in isolated rat liver mitochondria]. PMID- 3091880 TI - [A computer program for studying blood gases and acid-base problems]. PMID- 3091881 TI - [Various enzymatic activities in gastric carcinoma and intestinal metaplasia]. AB - Blood enzymatic activities in gastric carcinoma depend on the release from carcinomatous tissues, surrounding non-neoplastic tissues, increased permeability and necrosis of carcinomatous tissues. However, those enzymatic activities did not parallel the extent and macroscopic appearance of the tumor. Various enzyme proteins and gastrointestinal hormones concerning gastric carcinoma and intestinal metaplasia including pepsin, LDH, AFP, beta-glucuronidase, rGTP, lysozyme, ferritin, sialic acid, polyamine, CEA, Ca 19-9, collage, gastrin, immunoglobulin are discussed in this paper. The variation of enzymes and proteins occurring in gastric carcinoma and intestinal metaplasia are well documented. Some of them would be a useful indicator of diagnosis and treatment as a tumor marker. PMID- 3091882 TI - [Prevention of cancer chemotherapeutic agent-induced toxicity in postoperative breast cancer patients with glycyrrhizin (SNMC)]. AB - It is well known that all cell lines, normal as well as malignant, have a sensitivity to the growth inhibitory effect of IFN or IFN inducers. We speculated that the antiproliferative effects of the IFN inducer SNMC might help alleviate the uncomfortable side effects of cancer chemotherapeutic agent. Fifty-seven patients with postoperative breast cancer received MMF (mitomycin, methotrexate, futraful therapy with SNMC and 60 were given MMF alone. There was only one patient (1.7%) in the former group in whom the MMF chemotherapy was discontinued because of liver dysfunction; however, 15 patients (25%) in the latter group had to stop the therapy because of its side effects. Thus, there was a significant effect of SNMC in preventing the side effects of MMF chemotherapy. PMID- 3091883 TI - [RI angiography with 99mTc and 201T1-chloride scintigraphy in determining the effectiveness of intra-arterial infusion in chemotherapy of locally advanced and recurrent breast cancer]. AB - Eleven patients with local advanced and recurrent breast cancer were treated preoperatively with intraarterial infusion of chemotherapeutic agents. After the treatment, nine patients underwent radical mastectomy. RI angiography with 99mTc is a useful procedure for determining the correct position of the tips of an inserted cannula. The results of 201Tl-chloride scintigraphy have been found to be closely consistent with the results of the resected specimen histologically. Therefore, 201Tl-chloride scintigraphy is also a quite useful procedure for determining the effects of intraarterial infusion in cancer chemotherapy. PMID- 3091885 TI - [Thrombosis in various diseases: disseminated intravascular coagulation and thrombosis]. PMID- 3091884 TI - [Microangiopathic hemolytic anemia associated with gastric cancer]. AB - A case of advanced gastric cancer associated with metastatic carcinomatosis of the bone marrow, microangiopathic hemolytic anemia (MAHA) and disseminated intravascular coagulation (DIC) was reported. A 71-year-old woman complained of lumbago and general fatigue. At the time of admission, besides anemia, jaundice and a tendency to bleeding, the laboratory data showed, hyperbilirubinemia, elevated FDP and hemolytic anemia with fragmented red cells. The bone marrow was infiltrated by carcinoma, and an upper GI series examination showed Borrmann II type gastric cancer on the greater curvature of the antrum. After remission of both MAHA and DIC by mitomycin C, neothramycin and FOY, the patient successfully underwent subtotal gastrectomy. However, she died of cerebral hemorrhage on the 96th postoperative day. PMID- 3091886 TI - [Artificial organs and thrombosis: hemodialysis]. PMID- 3091887 TI - [Study of factor VIII complex in increased VIII:Ag cases]. PMID- 3091888 TI - Graves' disease associated with intersterno-costoclavicular ossification and pustulosis palmoplantaris--a case report and review of the literature. AB - It was shown that intersterno-costoclavicular ossification often appears together with pustulosis palmoplantaris by Sonozaki et al., 1980. We report here a patient of Graves' disease associated with intersterno-costoclavicular ossification and pustulosis palmoplantaris, and discuss the relationship with these conditions. PMID- 3091889 TI - A survived case of diabetic nonclostridial gas gangrene and the review of the literatures on microbiological findings. AB - Nonclostridial gas gangrene in diabetics results in poor prognosis. In this paper, a survived case of diabetic nonclostridial gas gangrene caused by Proteus vulgaris and Streptococcus faecalis is described and microbiological findings of 31 cases of the literatures including our own case were reviewed. Twenty of 31 cases died (64.5%). The microbiological findings in 30 cases revealed an average of 1.8 organism per case. Predominant aerobes were E. Coli (56.7%), Streptococcus faecalis (16.7%), aerobic Streptococcus and Proteus (both 13.3%) in that order. Anaerobes were found in 12 of 20 cases and isolated anaerobes were Bacteroides (8 cases) and Peptococcus (4 cases). The role of specific bacteria in causing severe form of nonclostridial gas gangrene in diabetics was suggested. PMID- 3091890 TI - A case of total thyroxine-binding globulin deficiency with Graves' disease: fluctuations of plasma triiodothyronine/thyroxine ratio. AB - A 37-year-old male with total thyroxine-binding globulin (TBG) deficiency associated with Graves' disease is described. Both TBG immunoreactivity and TBG capacity were not detectable in his serum. Serum concentrations of thyroxine binding prealbumin and albumin were normal. He was initially hyperthyroid. During methimazole-treatment he was maintained in an euthyroid state except for two short hypothyroid periods. His plasma triiodothyronine/thyroxine (T3/T4) ratios during both the untreated hyperthyroid and the methimazole-induced hypothyroid states were higher than those during his methimazole-induced euthyroid state. These findings on changes in his T3/T4 ratio accompanying thyroidal dysfunction were qualitatively comparable with those in patients with Graves' disease with normal TBG levels: that both untreated hyperthyroid and methimazole-induced hypothyroid patients showed higher T3/T4 ratios than methimazole-induced euthyroid patients. These results may provide indirect evidence that changes in hormonal secretion and conversion that raise T3/T4 ratio can occur in thyroidal dysfunctions even in the complete absence of TBG. PMID- 3091891 TI - Methamphetamine-induced behavioral alterations following repeated administration of methamphetamine. AB - Repeated administration of a large dose of methamphetamine (MA) (25 mg/kg, i.p. twice daily for 4 days) to mice enhanced locomotor activity and decreased stereotyped behavior following a subsequent injection of MA. Simultaneous determinations of catecholamines revealed a depletion of brain dopamine. The moderate doses of haloperidol significantly enhanced MA-induced locomotor activity in mice. A significant enhancement of MA-induced locomotor activity was observed in the rats pretreated with 6-hydroxydopamine into the striatum, and this effect correlated negatively with the striatal dopamine level. These results suggest that hypofunction of striatal dopaminergic neuron systems induced by repeated administration of MA may be one of possible mechanisms of the enhancement of MA-induced locomotor activity due to the decrease of stereotyped behavior. PMID- 3091892 TI - Stress and immune responses. IV. Adrenal involvement in the alteration of antibody responses in restraint-stressed mice. AB - We investigated the correlation between restraint stress-induced alteration of antibody responses and adrenal hormones. Adrenalectomy (Adx) blocked both the suppression of antibody response against T cell-dependent (TD) antigen and the enhancement of that against T cell-independent (TI) antigen in stressed mice. Adx also inhibited the atrophy of both thymus and spleen caused by restraint. Pre treatment of metyrapone, an inhibitor of adrenocortical steroid biosynthesis, had an effect that was similar to, but far weaker than that of Adx on stressed mice. The pre-administration of phenoxybenzamine, an alpha-adrenergic blocking agent, to mice prevented both the inhibition of antibody response to TD antigen and the decrease in spleen cell number of restrained mice. A similar effect was observed in mice pre-treated with 6-hydroxydopamine, an adrenergic neuron degenerating agent. However, no effects of these two agents were observed on the enhancement of antibody response to TI antigen. The suppressive effect of the antibody response to TD antigen was augmented by the pre-administration of propranolol, a beta-adrenergic blocking agent. These results suggest that the suppression of the function of T cells in restrained mice are attributed to the released adrenocortical and adrenal medullary hormones and activated sympathetic nervous system and that the enhancement of B cell function is due to the adrenocortical hormones. PMID- 3091893 TI - [A case of "gold lung" in the form of PIE syndrome]. PMID- 3091894 TI - Chemoprevention of mammary carcinogenesis: a comparative review of the efficacy of a polyamine antimetabolite, retinoids, and selenium. PMID- 3091895 TI - Tissue-type plasminogen activator in breast cancer: relationship with estradiol and progesterone receptors. AB - Plasminogen activator (PA) is an estradiol-inducible enzyme and therefore a potential marker for a functional estradiol receptor (ER) in human breast carcinomas. In this investigation tissue-type PA (t-PA) correlated significantly with both ER and progesterone receptors (PR) in human breast carcinomas. In contrast, neither total PA activity nor urokinase-like PA showed any significant correlation with either ER or PR. Other proteases such as a trypsin-like protease, a chymotrypsin-like protease, and cathepsin B also showed no correlation with ER and PR. It was concluded that the t-PA form of PA may be a marker for a functional ER in breast carcinoma and thus be of value in predicting hormone-dependent breast cancers. PMID- 3091896 TI - Consumption of dairy produce and alcohol in a case-control study of breast cancer. AB - In a French case-control study of 1,010 breast cancer cases and 1,950 controls with nonmalignant diseases, the risk of breast cancer was found to be positively associated with frequency of cheese consumption and the level of fat in the milk consumed. A negative association was found between frequency of yogurt consumption and the risk of breast cancer. No association was found between the consumption of butter and the risk of breast cancer. The positive association between a daily consumption of alcohol and the risk of breast cancer previously reported was not altered when dairy produce consumption was taken into account. PMID- 3091897 TI - Presence of activated T-cells with a T8+ M1+ Leu 7+ surface phenotype in invaded lymph nodes from patients with solid tumors. AB - The lymphocyte surface phenotype of lymph nodes from patients with larynx or urinary bladder carcinoma was investigated by using a panel of monoclonal antibodies. The phenotype pattern of lymphocytes from lymph nodes invaded by malignant cells (as assessed by histopathology) was different from that of the cells from noninvaded or normal control nodes. Although the proportion of natural killer cells or macrophages was similar in the 3 groups of lymph nodes, invaded lymph nodes contained a higher proportion of T-cells and a lower B-cell percentage. Furthermore, cells from invaded nodes comprised 15-20% of T3+ T8+ cells that coexpressed the M1 marker and, to some extent, also the Leu 7 marker. A large proportion of cells with multiple markers were activated, as shown by the expression of Tac and HLA-DR antigens. In 2 patients activated T8+ cells expressing also M1 and Leu 7 markers infiltrated the tumor site. The presence of these activated cells both in involved nodes and tumor mass may indicate that they originate in response to cancer. PMID- 3091898 TI - Human fibroblast chromatin states as effectors of the DNA-binding characteristics of benzo[a]pyrene anti-7,8-dihydrodiol 9,10-epoxide and two nonalkylating DNA binding molecules. AB - Pure populations of mitotic or nonmitotic diploid human fibroblasts (greater than 98% pure) were exposed to [3H]benzo [a]pyrene (CAS: 50-32-8) anti-7,8-dihydrodiol 9,10-epoxide: r-7,t-8 dihydroxy-t-9, 10-oxy-7,8,9,10-tetrahydrobenzo [a]pyrene (or anti-diol-epoxide). In addition, metaphase chromosomes, interphase chromatin, or naked DNA was isolated from the pure cell populations and then titrated to saturation with anti-diol-epoxide, chromomycin A3, or 3,8-diamino-5-ethyl-6 phenylphenanthridinium bromide (ethidium bromide). At saturation, anti-diol epoxide had covalently modified 1.5% of the total deoxyguanosine residues in naked DNA, and this was reduced to 29 and 15% of this level in saturating the available anti-diol-epoxide-binding sites in chromosomes or chromatin, respectively. A similar hierarchy of accessible binding sites (naked DNA greater than chromosomes greater than chromatin) was also observed for the noncovalent interaction of chromomycin A3 or ethidium bromide with the human cell DNA. Deproteinization of the chromosome or chromatin preparations returned the level of drug binding to that seen with naked DNA. The results clarify the association between proteins and DNA in human chromatin and suggest how cell-cycle-dependent changes in DNA-associated proteins or higher-order changes in protein-DNA conformation can act to alter the access of molecules to DNA-binding sites. PMID- 3091899 TI - Human primary colon carcinomas xenografted into nude mice. I. Characterization of plasminogen activators expressed by primary tumors and their xenografts. AB - Analysis was made of plasminogen activator (PA) activities present in 0.125% Triton X-100 extracts of human primary colon carcinomas and of their respective serial subcutaneous xenografts in nude mice. A correlation between tumor invasiveness and PA expression was observed in that primary tumors exhibiting clearly invasive growth patterns demonstrated high concentrations of PAs while subcutaneous xenografts, exhibiting noninvasive pseudobenign growth, contained very low levels of PA activity. The decrease in fibrinolytic activity observed in subcutaneous xenografts was not due to an increase in inhibitors of fibrinolytic activity. Immunologic characterization of PAs in tumor extracts showed that over 90% of human PA activity was of the urokinase type. Furthermore, tumor-derived urokinase was shown to be present in a proenzyme form. It was resistant to diisopropyl fluorophosphate (DFP) and was not inhibited by purified PA inhibitor. However, after its activation into urokinase by plasmin, it was completely inhibited by DFP and PA inhibitor. PMID- 3091900 TI - Complete tumor ablation with iodine 131-radiolabeled disialoganglioside GD2 specific monoclonal antibody against human neuroblastoma xenografted in nude mice. AB - The antibody 3F8, an IgG3 murine monoclonal antibody (MoAb) against disialoganglioside GD2, could target iodine-131 (131I) to established subcutaneous human neuroblastoma (NB) xenografts in BALB/c nude mice. 131I radiolabeled MoAb (0.125-1 mCi) was injected iv. Tumor radioactivity over time was calculated from scintigraphy, and radiation dose to individual tumors was calculated. Tumor shrinkage occurred only with 131I-labeled 3F8, but not with nonradioactive 3F8 or radiolabeled irrelevant antibody. While the tumor of the control mice enlarged by tenfold, the treated tumor showed over 95% shrinkage by 12 days. Both the rate of shrinkage and duration of tumor response were dose dependent. Calculated doses of more than 10,000 rad could be achieved. Only those tumors that received more than 4,200 rad were completely ablated without recurrence. Recurrent tumors were not antigen negative or radioresistant. These results confirmed the prediction based on imaging studies that human NB xenografts could be effectively eradicated with the use of 131I-labeled MoAb 3F8 with tolerable toxicities. PMID- 3091901 TI - Carcinogenicity of betel quid. III. Enhancement of 4-nitroquinoline-1-oxide- and N-2-fluorenylacetamide-induced carcinogenesis in rats by subsequent administration of betel nut. AB - The effect of betel nut on chemical carcinogenesis in the upper digestive tract and liver was examined in two different experimental models with ACI rats. The incidences of neoplasms and preneoplastic lesions of the tongue in animals given 5 ppm 4-nitroquinoline-1-oxide (4-NQO; CAS: 56-57-5) in the drinking water for 16 weeks and followed by 20% betel nut in the diet for 40 weeks were significantly higher than those in animals given 4-NQO alone. No enhancing effect from betel nut on the incidences of neoplastic and preneoplastic lesions in the upper digestive tract was found in animals administered 4-NQO for 12 weeks. The number of altered liver cell foci in rats given 200 ppm N-2-fluorenylacetamide (FAA; CAS: 53-96-3) in the diet for 8 weeks and followed by the betel nut diet for 16 weeks was significantly greater than that in animals fed the FAA diet alone. These results indicate enhancing effects of dietary administration of betel nut on oral carcinogenesis by 4-NQO and hepatocarcinogenesis initiated by FAA. PMID- 3091902 TI - Serum and urinary high density lipoproteins in glomerular disease with proteinuria. AB - The serum lipoprotein concentrations, including high-density lipoprotein (HDL) subfractions and apolipoproteins Al and B were measured in 21 patients (14 male and seven female) with nephrotic range proteinuria (greater than 3g/24hr), well maintained renal function (creatinine clearance greater than 35 mliter/min/1.73m2) and biopsy-proven primary glomerular disease. In these, and in a further five patients (creatinine clearance greater than 15 mliter/min/1.73m2), urinary apolipoprotein Al output was determined. Total HDL cholesterol was similar in patients and controls, but in male patients, HDL2 was low (0.54 +/- 0.10 mmole/liter, mean +/- SEM) compared to controls (0.75 +/- 0.04 mmole/liter, P less than HDL3 was high (0.81 +/- 0.07 in patients and 0.63 +/- 0.02 mmole/liter in controls, P less than 0.01). In women, there was a similar tendency for HDL2 to be lower in patients (0.68 +/- 0.18 mmole/liter) than in controls (0.85 +/- 0.10 mmole/liter). Multiple regression analysis revealed that major determinants of the urinary apolipoprotein Al output were the urinary protein output and selectivity index (multiple r = 0.85). Furthermore, some patients lost apolipoprotein Al into their urine at rates indicating increased production of apolipoprotein Al in the nephrotic syndrome. The serum HDL subfraction concentrations in the nephrotic syndrome could be explained by a combination of increased HDL production and increased urinary loss of low molecular wt HDL. PMID- 3091904 TI - Protein glycosylation as an indicator of blood glucose control using furosine determination. PMID- 3091905 TI - [Effect of using nitroderm in ischemic heart disease]. PMID- 3091906 TI - [Graduate and continuing education of the operating room nursing personnel: aims and limits--from a nursing viewpoint]. PMID- 3091903 TI - Potential role of carnitine in patients with renal insufficiency. AB - Carnitine metabolism is altered in renal insufficiency and influenced by the treatment modalities. Chronically uremic patients with end-stage renal disease under conservative therapy, hemodialysis, or peritoneal dialysis show low, normal, or elevated serum levels of TC and a distorted pattern of FC, SCAC, and LCAC. HD induces a marked depletion of FC, while predialytic elevated SCAC and LCAC are in the normal range at the end of dialysis treatment. All carnitine fractions rapidly return to predialysis levels 6 h after HD due to a transport of carnitine from muscle stores to plasma pool. Muscle carnitine content is elevated in chronic uremic patients under conservative therapy. Normal or decreased levels are observed in patients on long-term HD treatment. In addition, weekly losses of carnitine in patients undergoing HD or peritoneal dialysis do not exceed urinary carnitine excretion of CO. Supplementation with currently recommended doses (1-2 g L-carnitine i.v. at the end of each HD) is followed by a marked rise in plasma carnitine levels, suggesting limited carnitine utilization in uremia. Therefore, lower carnitine doses and modified application regimens should be considered to avoid exaggerated plasma levels of carnitine and carnitine esters. Furthermore, carnitine application has been reported to show beneficial, worsening, or no effect on the deranged lipid metabolism of the uremic patients. In patients undergoing CAPD or IPD predominantly normal serum carnitine levels have been reported. On the other hand, SCAC and LCAC esters are markedly elevated in these patients. After kidney transplantation the pattern of carnitine fractions is fully normalized in patients with plasma creatinine less than or equal to 120 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3091907 TI - [Training as an operating room technician in the Netherlands]. PMID- 3091908 TI - [The edentulous mouth--why do patients have to enter the anesthesia of surgical departments without their dental prostheses?]. PMID- 3091909 TI - [The tasks of the nurse during the use of laser beams in endoscopy]. PMID- 3091910 TI - [Gene technology--a blessing? Thoughts on gene technology from the viewpoint of a nurse and father of a family]. PMID- 3091911 TI - [Women and reproductive technologies. Women and gene technologies]. PMID- 3091912 TI - [Anything goes--each offer produces its own demand. The report of the BENDA COMMISSION]. PMID- 3091913 TI - [Gene technology in the competitive field of political interest groups]. PMID- 3091914 TI - [Gene technology/reproductive technology--a new form of family politics?]. PMID- 3091915 TI - [Of the dignity of nascent life. Extracorporeal fertilization, heterologous pregnancy and genetic counseling. Help from the German protestant church towards formation of ethical decisions]. PMID- 3091916 TI - [Ways to apply the bordello model to human reproduction by means of the new reproductive technologies]. PMID- 3091917 TI - [Modern nutritional technics expand and simplify enteral feeding]. PMID- 3091918 TI - Pyruvate carboxylase defect: metabolic studies on cultured skin fibroblasts. AB - Oxidative studies using a number of radioactive carbon-labelled substrates on intact cultured skin fibroblasts from a patient with pyruvate carboxylase deficiency revealed dysfunction of the Krebs cycle. The suppression of CO2 production from aspartate but not glutamine strongly suggests that the defective function lies in the aspartate-malate shuttle. Furthermore, there is an unusual dependence on glutamine for the maintenance of growth of the patient's cells compared to normal cells. Glutamine could not be replaced by aspartate supplementation. A secondary defect resulting in accumulation of lipid material was also demonstrated in this study. It is speculated that the intracellular level of oxaloacetate may also be diminished in the patient's cells. Oxaloacetate is primarily generated by the carboxylation of pyruvate catalysed by pyruvate carboxylase. PMID- 3091919 TI - Glucose metabolism in fibroblasts from patients with erythrocyte hexokinase deficiency. AB - Four different hexokinase (HK) isoenzymes are distributed in different proportions in human tissues. Fibroblasts contain HK type I as the predominant glucose phosphorylating activity, the same isoenzyme that predominates in red blood cells (RBC). We have established cell lines from two patients homozygous for RBC HK deficiency but carrying different mutations. In one case (HK-Melzo) the residual RBC enzyme shows a marked heat instability but possesses normal kinetic and regulatory properties; in the other (HK-Napoli), the enzyme is characterized by an increased Ki for glucose-1,6-diphosphate. These properties are also retained by the fibroblasts' hexokinase. Glucose utilization by cultured fibroblasts from these patients was markedly reduced in the cell lines where HK deficiency was more pronounced. However, cells with only 30% HK activity retained their full ability to utilize glucose in the hexose monophosphate pathway. This was shown to be true not only under basal conditions but also in the presence of oxidative agents such as methylene blue. Significant reduction of the ATP level was also found in HK-Melzo fibroblasts. Thus, HK deficiency is associated with reduced glucose utilization and normal hexose monophosphate shunt rates. Results previously obtained on RBC support similar conclusions. PMID- 3091920 TI - Gonadal function in patients with galactosaemia. AB - Gonadal function was followed in 26 females and 12 males with galactosaemia due to deficiency of the enzyme galactose-1-phosphate (Gal-1-P) uridyl transferase over a 4 year period. Gonadal function was normal in males, but all females except two had evidence of acquired ovarian failure. Twelve females with ovarian failure documented at the beginning of this study continued to have either primary or secondary amenorrhoea on follow-up. Five of six patients, who previously had normal gonadal function developed either hypergonadotrophic hypogonadism or an abnormal response to gonadotrophin-releasing hormone (LRH) indicative of acquired ovarian damage. Seven of eight female patients, 1-12 years of age, who were evaluated for the first time had an exaggerated release of gonadotrophins during LRH stimulation tests diagnostic of gonadal insufficiency. The pathogenesis of ovarian failure remains unknown, but it appears likely that galactose or Gal-1-P is toxic to the ovary. The source of galactose metabolites, which may begin to accumulate prenatally and continue to damage the gonad in the postnatal period, is likely to be derived from the diet and from the endogenous synthesis of Gal-1-P from glucose via a variety of metabolic pathways. The testis appears to be relatively resistant to the effects of abnormal galactose metabolism. PMID- 3091921 TI - The role of steroid metabolic profiling as an aid in the diagnosis of familial precocious puberty, a subgroup of true precocious puberty. AB - We report the results of a study of a rare form of true precocious puberty in a family with a history of the condition. Only the male members manifest the trait, whereas it appears to be carried by both males and females. Routine urinary steroid analysis rapidly eliminated most of the classical enzyme defects associated with premature sexual maturation. Further investigation of urinary steroid extracts using gas chromatography and gas chromatography-mass spectrometry revealed essentially normal prepubertal androgen values for the proband A at 4 years of age, and for his affected and carrier relatives when compared with healthy age-matched individuals. While his plasma gonadotropin levels were in the prepubertal range, his plasma testosterone value was significantly elevated with values just below the normal range for an adult male. This is the fourteenth reported family with a vertical pattern of familial sexual precocity, but the first to have a steroid profile. Analysis suggests sex-limited autosomal dominance with a greater than 90% penetrance. The elevated plasma testosterone concentration, prepubertal plasma gonadotropin concentration, minimal histopathologic evidence of gametogenesis and only moderate increase in testicular volume over the five-year course of follow-up support a diagnosis of the recently described condition of familial gonadotropin independent sexual precocity. The gas chromatography-mass spectrometry urinary profiling shows elevated cortisol output but otherwise normal adrenal function. PMID- 3091922 TI - Partial lyonisation of steroid sulphatase gene in single hair roots. AB - Steroid sulphatase (STS) activity was measured in single hair roots from 9 patients with X-linked ichthyosis, 7 obligate heterozygotes, 12 male controls and 12 female controls. STS activity was deficient (less than 0.3 pmol dehydroepiandrosterone (DHEA) in 5 h per hair root) in the patients as compared to male controls (4.6 +/- 1.8 pmol DHEA in 5 h per hair root). All single hair roots from obligate heterozygotes showed STS activity (3.0 +/- 0.9 pmol DHEA in 5 h per hair root). Female controls had a significantly higher STS activity (6.0 +/ 1.8 pmol DHEA in 5 h per hair root) than male controls (p less than 0.05) and heterozygotes (p less than 0.001). Both the female-male sex ratio of control STS activity (1.3) and the absence of STS-deficient hair roots in heterozygotes confirm previous evidence for incomplete lyonisation of the X-linked steroid sulphatase gene. PMID- 3091923 TI - Ornithine transcarbamylase deficiency: a case with a truncated enzyme precursor and a case with undetectable mRNA activity. AB - The cell-free translation of ornithine transcarbamylase (OTC) mRNA from the livers of two heterozygous patients (from different families) with OTC deficiency was performed. The enzyme activities and the immunoreactive proteins in both patients were about 5% of those in controls. Immunoblotting assay of liver extracts from both patients showed decreased amounts of the OTC protein. The mRNA from the liver of patient 1 directed the synthesis of a very small amount of OTC precursor of normal subunit size (40,000 Da), whereas that from patient 2 directed the synthesis of small amounts of two distinct in vitro products; one was 40,000 Da and the other was about 30,000 Da. The in vitro product of normal precursor synthesized with mRNA from patient 2 was converted to mature-sized OTC by isolated rat liver mitochondria, whereas the smaller product was degraded during the incubation with the mitochondria. These results indicate that in both patients the translatable level of mRNA for active OTC from liver cells was much lower than that in the controls. The results also suggest that in patient 2, the smaller product presumably derived from an abnormal gene could not be transferred to the mitochondria. PMID- 3091924 TI - A new patient with hyperornithinaemia, hyperammonaemia and homocitrullinuria treated early with low protein diet. AB - The characteristic biochemical disturbances of the amino acid and pyrimidine metabolism are described and illustrated by the first case of the HHH syndrome reported in Norway. The disorder was treated with a low protein diet at an early age and the patient developed normally on this diet. PMID- 3091925 TI - Direct identification of propionylcarnitine in propionic acidaemia: biochemical and clinical results of oral carnitine supplementation. AB - Urinary short-chain acylcarnitine in a patient with propionic acidaemia and low levels of free carnitine was found to consist mainly of propionylcarnitine. The compound was isolated by sequential paper and thin layer chromatography and identified by ammonia desorption chemical ionization mass spectrometry. Treatment of the patient with oral carnitine supplements led to a near-normalization of the plasma free carnitine concentrations and an increase in his muscle tone. The propionylcarnitine excretion rose and there was a simultaneous decrease in the methylcitrate output. Carnitine treatment did not prevent the occurrence of an episode of metabolic decompensation. PMID- 3091926 TI - Non-ketotic hyperglycinaemia due to a deficiency of T-protein in the glycine cleavage system in liver and brain. AB - Non-ketotic hyperglycinaemia was diagnosed in a girl at 3 weeks of age because of the typical clinical presentation, the elevated glycine concentration in urine, plasma and especially in cerebrospinal fluid and the normal profile of organic acids in urine. An EEG showed the typical burst suppression pattern. Therapeutic approaches with either pyridoxine (50 mg d-1) alone or in combination with N5 formyltetrahydrofolate (3 X 3 mg d-1) or with strychnine (0.3 mg per kg body weight) did not result in improvement. In postmortem liver and brain of the patient the overall activity of the glycine cleavage system was deficient; examination of the activity of the individual components of the glycine cleavage system in the tissues revealed that the activity of the T-protein was undetectable, whereas that of the other components and of lipoamide dehydrogenase was normal. PMID- 3091927 TI - Plasma chromium and manganese levels in treated PKU patients. PMID- 3091929 TI - Approaches to the study of long term care. PMID- 3091928 TI - Liver transplantation in a 23-year-old tyrosinaemia patient: effects on the renal tubular dysfunction. AB - Orthotopic liver transplantation was performed on a 23-year-old female with hereditary tyrosinaemia. The disorder was diagnosed at 7 years of age due to severe rickets, and the patient was treated with a diet restricted in phenylalanine and tyrosine. Nineteen months before the transplantation she had an acute episode of diffuse gastrointestinal bleeding due to portal hypertension. Three subsequent bleeding episodes with accompanying ascites and signs of encephalopathy were considered life-threatening. Nine months after the liver transplantation the patient is well, but serum transaminases are slightly elevated. Without dietary restrictions serum tyrosine and inorganic phosphate are normalized, no succinylacetone can be detected in serum, and urinary excretion of p-hydroxyphenyllactate and p-hydroxyphenylpyruvate is normal. Excretion of amino acids, glucose and beta 2-microglobulin decreased significantly after the transplantation but is still elevated. The succinylacetone concentration in urine is about 20% of the preoperative level. After an oral tyrosine load, succinylacetone excretion increased sevenfold but no deterioration of the renal tubular function was observed and no tyrosine metabolites were detectable in serum. The findings indicate that the defective tyrosine metabolism occurs in the kidneys, but does not produce tubular dysfunction. The residual tubular dysfunction of the patient is probably due to irreversible damage of the tubular epithelium. PMID- 3091930 TI - The crisis of increased life expectancy. PMID- 3091931 TI - Alzheimer's disease and long term care. PMID- 3091932 TI - New national views of community long term care. PMID- 3091933 TI - Policy issues in long term care: a model of transitions. PMID- 3091934 TI - Planning for the long term care service needs of South Carolina's elderly citizens. PMID- 3091935 TI - South Carolina community long term care: coordinating research and service. PMID- 3091936 TI - Does the purity of intraportal islet isografts affect their endocrine function? AB - The effect of collagenase digested pancreatic tissue upon the endocrine function of intraportal islet isografts has been studied in rats. The ability of transplanted islets to restore normoglycemia in recipients was not affected by tissue contamination, but the insulin response to glucose challenge 12 weeks after transplantation was negatively correlated with the amylase content of this additional tissue transplant. All animals receiving a single dispersed pancreas died within 24 hr. These findings are discussed in relation to transplantation of the dispersed pancreas in human. PMID- 3091937 TI - Structure of lysine adducts with 16 alpha-hydroxyestrone and cortisol. AB - Recent studies indicate that steroids containing a vicinal hydroxyketone moiety can react with proteins both in vitro and in vivo to form covalent addition products. This reaction is non-enzymatic and occurs via the Heyns rearrangement of an initial Schiff base adduct between the steroid carbonyl and the epsilon amino group of lysine residues. The present study describes the synthesis, isolation, and structural analysis of model adducts prepared by the incubation of 16 alpha-hydroxyesterone or cortisol with NaCNBH3 and lysine derivatives blocked in the N alpha-position. The product formed from the reaction of 16 alpha hydroxyesterone and lysine was found to have the structure predicted for a reduced Schiff base between these molecules. A stable, cortisol-lysine adduct was similarly synthesized and isolated. This conjugate was found not to be the expected reduced Schiff base but rather a C-20 cyano amine. This compound most likely was formed by the nucleophilic addition of cyanide during the course of the incubation. The observation that the cortisol-lysine Schiff base is not reducible with NaCNBH3 accounts for the observation that the incorporation rate of glucocorticoids into proteins is not increased by the presence of NaCNBH3. PMID- 3091938 TI - Differential effects of follicle-stimulating and luteinizing hormones on testosterone production by mouse testes. AB - In adult mice, direct intratesticular injection of ovine follicle-stimulating hormone (o-FSH-13; AFP 2846-C, from NIAMDD, less than 1% LH contamination) at 10, 100 or 1000 ng significantly elevated concentrations of testosterone (T) within the testis. These effects were rapid, with peak values attained by 15 min, and transient, with return to values comparable to that in the contralateral, saline injected testis within 90 min. Intratesticular injection of FSH (1 microgram) significantly increased testicular T levels in 15- and 60-day old mice. This contrasted with the effects of intratesticular administration of human chorionic gonadotropin (hCG), which stimulated T production significantly at 30 days of age through adulthood. In adult mice, the equivalent LH to the possible contamination in the FSH preparation (1 ng) had no effect. Intratesticular injection of 10 ng LH produced comparable stimulation to that by 100 ng FSH (approximately 7-fold). Systemic pre-treatment with a charcoal-treated porcine follicular fluid (PFF) extract for 2 days reduced plasma FSH levels [86 +/- 17 (5) vs 700 +/- 8 (6); P less than 0.05], but had no effect on plasma LH. Twenty-four hours after the last treatment, the response to intratesticular injection of hCG (2.5 mIU), FSH (100 ng) or LH (10 ng) was also significantly attenuated in these mice. Intratesticular injection of PFF had no direct effect on testicular T levels. In vitro T production in the presence of hCG, LH or FSH were differentially affected by the concentrations of calcium (Ca2+) or magnesium (Mg2+) in the incubation media. The stimulatory effects of FSH were apparent at significantly lower levels of Ca2+ or Mg2+, than were those of LH or hCG. The results of these studies indicate that FSH is capable of stimulating testicular T production. Furthermore, the responsiveness to FSH is qualitatively different than that to LH/hCG in terms of the age pattern, as well as the dependence on Ca2+ or Mg2+. In addition, plasma FSH levels appear to influence testicular responsiveness to direct exogenous administration of gonadotropins. These studies indicate that FSH stimulation of T production can be differentiated from those of LH, and that these effects of FSH can be observed under physiological conditions. PMID- 3091939 TI - Purification of NADPH-cytochrome P-450 reductase from microsomal fraction of rat testes, and its chemical modification by tetranitromethane. AB - NADPH-cytochrome P-450 reductase in rat testicular microsomal fraction was solubilized by trypsin, and purified to apparent homogeneity in polyacrylamide gel electrophoresis. Molecular weight of the enzyme was estimated to be about 70,000 by SDS-polyacrylamide gel electrophoresis. Km values were estimated as 18 microM for cytochrome c, 17 microM for dichlorophenol indophenol (DCPIP), 50 microM for K3Fe (CN)6 and 1.7 microM for NADPH. The cytochrome c reducing activity of the purified preparation was decreased by tetranitromethane (TNM), a reagent for nitration of tyrosine residues in a protein. The inactivation exhibited pseudo-first-order kinetics. A plot of log kapp vs log [TNM] gave a straight line with slope = 1.05, indicating the reaction of one modifier molecule in the inactivation process. The decrease of the reducing activities for DCPIP and K3Fe(CN)6 by TNM progressed more slowly than that for cytochrome c. The inactivation of cytochrome c reduction was protected completely by 0.1 mM NADP(H) and partially by 0.1 mM DCPIP and cytochrome c. No preventive change of the inactivation by TNM was observed by addition of NAD+ or testosterone. On the other hand, the differential modification by DTNB, TNM and DTT indicated that there were amino acid residues modified by TNM, such as tyrosine residues, at or near the active-site of the NADPH-cytochrome P-450 reductase. PMID- 3091940 TI - Effect of genetically defined oocyte depletion on production of androgens and oestrogens by ovaries of suckling mice. AB - Steroid production and histological features of ovaries were compared either among normal +/+ mice of 3-12 days of age or among 12-day old mutant mice with various degrees of oocyte depletion. Whole ovaries were cultured in the medium containing [3H]progesterone and hCG or 4-androstene-3,17-dione and FSH; amounts of [3H]androgens or oestrogens released from the ovaries were assayed. FSH responsive aromatase activity was detectable in ovaries of +/+ mice on day 3 after birth (2.6 +/- 0.4 pmol/2 ovaries/48 h), but the activity producing androgens from progesterone, under stimulation of hCG, was not detectable even on day 6 after birth (less than 0.1 pmol/2 ovaries/48 h). The androgen-producing activity appeared on day 9 after birth (1.16 +/- 0.25 pmol/2 ovaries/48 h), when follicles with more than two layers of granulosa cells developed. The ovaries of 12-day old Sl/Slt mice contained a considerable number of follicles with a single layer of granulosa cells, but did not contain any follicles with more than two layers of granulosa cells. The ovaries of Sl/Slt mice possessed aromatase activity (3.3 +/- 0.4 pmol/2 ovaries/48 h) but, not androgen-producing activity (less than 0.1 pmol/2 ovaries/48 h). The present results suggest that development of follicles with more than two layers of granulosa cells may induce the activity producing androgens from progesterone under stimulation of LH in suckling mouse ovaries, though the FSH-responsive aromatase activity is present even in follicles with a single layer of granulosa cells. PMID- 3091941 TI - Solubilization and partial purification of aromatase from chicken ovary. AB - Aromatase, the cytochrome P-450 that converts androgen to estrogen, has been solubilized from chicken ovarian microsomes with the nonionic detergent Emulgen 913. Following chromatography on gel filtration, anion exchange, dye affinity, and hydrophobic media, ovarian aromatase is purified up to 27-fold with 10-15% recovery. Separation of the cytochrome P-450 aromatase from NADPH cytochrome P 450 reductase is achieved during the purification. The partially purified enzyme is stable for as long as 6 months when frozen in liquid nitrogen in buffer containing dithiothreitol, glycerol, Emulgen and 150 mM KCl. PMID- 3091942 TI - Nonsteroidal substances that affect serum free testosterone. AB - Several steroid hormones affect free testosterone (FT) levels in blood by competing with testosterone for binding sites on testosterone-binding globulin (TeBG). However, the effect of endogenous nonsteroidal substances in serum has not been reported. Some of these potential modifiers of FT were studied using equilibrium dialysis. Nonesterified fatty acids at 0.9 mM elevated FT approx 10% at pH 7.4. Investigation of the curvilinear relationship of percent FT (pFT) vs pH showed that pH-dependent changes of testosterone binding to albumin were responsible for a small linear increase in pFT with decreasing pH. The greater portion of the curvilinear increase of pFT with decreasing pH was due to fatty acids competing with testosterone for TeBG binding sites. Ketone bodies significantly affected FT (7.5% elevation) only at levels found in diabetic ketoacidosis. Sodium ions improved binding 11% when 7 mM was compared to 157 mM sodium, but physiological changes in sodium would result in only +/- 1% changes in FT. Very low levels (0.03 mM) of calcium may be essential for normal testosterone binding to TeBG since 1.0 mM EGTA raised FT by 75%. This study shows that dialysis at 37 degrees C should not be performed overnight, that thimerosol should not be used as a preservative, and that the dialysis buffer should contain physiological concentrations of sodium and calcium. PMID- 3091943 TI - [The influence in the rat of counter-irritation by turpentine on the leukocyte content of exudates induced by sponge implants]. AB - In normal rats, PGE1, arachidonic acid, indomethacin and diclofenac did not modify the leucocyte content of sponge exudates withdrawn 4 hours after implantation while arachidonic acid increased the level in PGE2 and indomethacin reduced it. The leucocyte content of sponges exudates withdrawn 18 hours after implantation was not modified by PGE1 and TXB2, but diminished by indomethacin and NDGA and increased by arachidonic acid. As the chemotactic effect of arachidonic acid was slightly reduced by indomethacin and abolished by NDGA, it could depend on the formation of lipoxygenase derivatives. In normal rats, the leucocyte content of sponge exudates withdrawn 18 hours after implantation was increased slightly by normal serum and largely by serum from turpentine-treated rats. The blood leucocyte content was not modified in turpentine-treated rats. However in these rats, the leucocyte content of sponge exudates was low comparatively to the leucocyte content in normal rats. This low level was not affected by indomethacin, arachidonic acid and normal serum. The leucocytes of turpentine-treated rats seem to be desensitizated towards chemotactic factors. Similar desensitization was observed in rats treated by iota carrageenan. PMID- 3091944 TI - [The effects of different inhibitors on bronchoconstriction induced by leukotriene D4 in isolated and perfused guinea pig lung]. AB - The effects of selective inhibitions of both cyclo-oxygenase and lipoxygenase pathways were studied in the isolated, perfused and ventilated guinea-pig lungs. Leukotriene D4 (0.3 nmol) induced a significant bronchoconstriction. This effect was significantly inhibited by IPL 55712 (a SRS-A antagonist) and by Imidazole or Dazoxiben (specific thromboxane synthetase inhibitors), but aspirin and indomethacin were without significant effect on this broncho-constriction. Our results suggest that the principal component of leukotriene D4 induced bronchoconstriction in guinea-pig lungs is primary. PMID- 3091945 TI - Properties of 17- to 19-day-old chick embryo liver microsomes. Induction of cytochrome P-450, effect of storage at low temperature, and resistance to lipid peroxidation. AB - Maximal hepatic cytochrome P-450 levels were induced in the 17-day-old chick embryo (four to five times control) with a dose of sodium phenobarbital of 6 mg/egg/day for 2 days. Similar levels of hepatic cytochrome P-450 were induced with a dose of propylisopropylacetamide of 4 mg/egg/day for 1 day. Chick embryo hepatic microsomes from phenobarbital-pretreated or from untreated chick embryos could be stored for periods of 14 days at -70 degrees C without a decrease in cytochrome P-450 levels. Moreover, no significant differences was discerned between the degree of suicidal inactivation of chick embryo hepatic cytochrome P 450 by 3,5-diethoxycarbonyl-1,4-dihydro-2,6-dimethyl-4-ethylpyridine in fresh and stored microsomes. Unlike rat hepatic microsomes, chick embryo hepatic microsomes do not undergo lipid peroxidative loss of cytochrome P-450 and heme when incubated in the presence of NADPH. PMID- 3091946 TI - Cost analysis of arterial branching in the cardiovascular systems of man and animals. AB - A new scheme is presented whereby data on arterial branching can be interpreted in terms of direct cost to the physiological system. The scheme makes it possible to assess, at a glance, the true degree of optimality of an arterial network. Departure from optimality is indicated in terms of cost, rather than in terms of the difference between theoretical and measured branching angles. The scheme is applied to several groups of biological data and new conclusions are reached with regard to their degrees of optimality. PMID- 3091947 TI - Quantification of regional platelet and calcium deposition on pericardial tissue valve prostheses in calves and effect of hydroxyethylene diphosphonate. AB - Mitral valves were replaced with 25 mm bovine pericardial tissue valve prostheses (Ionescu-Shiley) in 45 calves (23 controls and 22 treated daily with hydroxyethylene diphosphonate). Before being killed 1, 14, 30, and 90 days later, the calves received In-labeled autologous platelets intravenously. Regional variations in platelet deposition were measured by a new technique. Thrombus was noted early on the flexion zone of the valve; with time it increased on the free edge and central zone. Platelet deposition was initially high on the flexion zone, attachment zone, sewing ring, and perivalvular tissue but decreased with time. Hydroxyethylene diphosphonate treatment tended to decrease platelet deposition in all zones. Calcium content was high in thrombus and increased in all zones with time, in both groups, but the deposition was less in the group treated with hydroxyethylene diphosphonate. Collagenous tissue and adherent thrombus appear to provide nucleation sites for calcification. PMID- 3091948 TI - Effect of cardiac operation on platelets. AB - The effect of extracorporeal circulation on platelet count and size (mean platelet volume) was studied in 65 patients (nine bleeders and 56 nonbleeders). In addition to the above, in 20 of the patients platelet aggregation response to adenosine diphosphate, collagen, and ristocetin was measured. Platelet counts dropped postoperatively both in the bleeder and in the nonbleeder groups. The difference between them was not significant. However, the bleeders had a significantly lower mean platelet volume (7.7 +/- 0.84 versus 8.68 +/- 1.1 fl) and lower volume percentage of platelets in whole blood (0.075% +/- 0.02% versus 0.116% +/- 0.04%) (p less than 0.05) than the nonbleeders. None of the bleeders had a volume percentage of platelets in whole blood higher than 0.095%. All 20 patients studied for platelet functions had an abnormal postoperative aggregation response to adenosine diphosphate, collagen, and ristocetin. Three patterns of disturbed response to ristocetin were observed: grade I, delayed onset (14 patients); grade II, incomplete aggregation (five patients); and grade III, total lack of aggregation (one patient). All patients with delayed-onset response to ristocetin had a normal bleeding time, whereas the six patients with grade II and III responses had prolonged bleeding times and three of them had clinically significant bleeding. Factor VIII procoagulant activity, factor VIII-related antigen, factor VIII-ristocetin cofactor, and factor VIII two-dimensional electrophoresis were found normal, which suggests that the von Willebrand-like reaction to ristocetin observed in this study was caused by a defect in platelet membrane rather than by factor VIII changes. PMID- 3091949 TI - Improved detection of terminal transferase (TdT): the use of detergents on glutaraldehyde-fixed non-dehydrated cells prevents denaturation and diffusion artifacts. AB - TdT as an intranuclear enzyme mainly of immature lymphoid cells is commonly determined immunologically using air-dried cell smears fixed with methanol. Both cell dehydration and alcohol fixation were found here to denature TdT and surface antigens. This could be prevented by using non-dehydrated cells bound electrostatically to poly-L-lysine-coated slides, fixed minimally with glutaraldehyde and rendered permeable to antibodies by the non-ionic detergent Brij 56. Crosslinking glutaraldehyde in addition prevented diffusion of TdT to extranuclear sites. By avoiding artifacts of denaturation and diffusion, a higher sensitivity in the detection of TdT was achieved despite considerably lower quantities of antibody. PMID- 3091950 TI - Extracorporeal gas exchange: design and techniques. Proceedings of a workshop symposium. Paris, June 20-21, 1985. PMID- 3091951 TI - A monitoring system for controlling vital and blood gas parameters during extracorporeal CO2 removal. PMID- 3091952 TI - The effects of respiratory support on surfactant metabolism: a study in rabbits. PMID- 3091953 TI - Clinical comparison between four modern membrane oxygenators: Bentley CM 40/50, COBE CML, Sci Med 3500-2A and Travenol LPM 50. AB - The devices with flat polypropylene membranes can be primed simpler and faster, than devices with the capillary membranes or with silicone rubber membranes. These two devices also offer more protection against venous air admixture and leaking of bubbles across the membrane. From hematologic standpoint there was no clear advantage of one particular device over another. PMID- 3091954 TI - Clinical experience with modern membrane oxygenators. PMID- 3091955 TI - Composite membranes for extracorporeal gas exchange. PMID- 3091956 TI - Support bypass in the treatment of hypercapnia in severe bronchospasm (a case report). PMID- 3091957 TI - Dynamic model of gas exchanges during cardiopulmonary bypass. PMID- 3091958 TI - Modelling of CO2 removal in membrane lungs. PMID- 3091959 TI - Development of a small compact circuit for extracorporeal CO2 removal. PMID- 3091960 TI - Physiological aspects of extracorporeal CO2-removal in dogs and sheep with regard to clinical application. PMID- 3091961 TI - In vivo evaluation of a vortex-mixing polypropylene membrane lung optimized for CO2 removal. Preliminary results. PMID- 3091962 TI - Extracorporeal elimination of carbon dioxide using a surface heparinized vein-to vein bypass system. PMID- 3091963 TI - Fiber optics coupled fluorescence sensors for continuous monitoring of blood gases in the extracorporeal circuit. PMID- 3091964 TI - Elevated histamine content of lung lavage in human asbestosis. PMID- 3091965 TI - Specific diffusing capacity (DL/VA) as a measure of the lung's diffusing characteristics: prediction formulas for young adults. PMID- 3091966 TI - Concentration and distribution of soluble and insoluble macromolecules from sputum: a possible estimation of the hydration of sputum macromolecules. PMID- 3091967 TI - Treatment options for insulin-dependent diabetes mellitus: a comparison of the artificial endocrine pancreas, continuous subcutaneous insulin infusion, and multiple daily insulin injections. AB - The essential components of an intensive insulin therapy program are maintenance of stable basal concentrations of insulin between meals and appropriate, timely increases in the concentration of circulating insulin after ingestion of meals. Closed-loop systems that both continuously monitor the plasma glucose concentration and continuously infuse insulin intravenously can reproducibly achieve near-normal glycemia in patients with insulin-dependent diabetes mellitus. Near-normal glycemia can also be achieved with use of a continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) of regular insulin combined with a single injection of slowly absorbable insulin in properly selected, compliant and cooperative patients. The frequency of hypoglycemia is similar with CSII and MDI. The risks of catheter-associated problems and ketoacidosis, however, are greater with CSII than with MDI. In contrast, the basal concentration of insulin can be more reproducibly and rapidly regulated with CSII than with MDI. The ratio of risk versus benefit associated with intensive insulin therapy with either CSII or MDI is currently unknown. PMID- 3091968 TI - Mycoplasma pneumoniae infections: diagnosis based on immunofluorescence titer of IgG and IgM antibodies. PMID- 3091969 TI - The mononuclear phagocyte system: the heart of host defense. PMID- 3091970 TI - A super-gene family in the immune system. PMID- 3091971 TI - [Cost benefit analysis in organ transplantation]. PMID- 3091972 TI - [Does sex hormone balance modify the pathogenesis of laryngeal cancer?]. AB - Although there are some pointers towards dependence of pathogenesis of laryngeal cancer on hormone metabolism, proof for this assumption is still missing. We studied hormone metabolism of 43 patients with laryngeal disease (testosterone, oestradiol, FSH, LH, prolactin). We subdivided the patients into two groups: 20 patients with squamous cell carcinoma and 23 patients with non-malignant diseases. No differences were seen between the two groups on statistical evaluation of the data. We could not prove any hormonal dependence, which might have had a therapeutical impact on the administration of antiandrogen drugs. PMID- 3091973 TI - [Leukocyte scintigraphy in inflammatory bowel diseases--a new method for diagnosis and follow-up?]. PMID- 3091974 TI - Antiulcer effect of rioprostil, a prostaglandin E1 analog, in combination with antacid. AB - Rioprostil, a primary alcohol prostaglandin E1 analog, is currently undergoing clinical evaluation for use in the treatment of peptic ulcer disease. Since antacids are often used in conjunction with other antiulcer agents, studies were conducted to determine if concomitantly administered antacid modifies the antiulcer activity of rioprostil. This investigation showed that concomitant administration of antacid (0.25-1.0 ml Maalox) does not inhibit the ability of rioprostil (0.125-4.0 micrograms/kg, p.o.) to prevent ethanol-induced gastric lesions in rats. The antiulcer effect of the drug combination was additive, suggesting that each compound acts independently to prevent gastric bleeding. These results in animals suggest that clinically the use of antacid will not compromise the efficacy of rioprostil and that the combination may be a useful mode of therapy for the treatment of peptic ulcer disease. PMID- 3091975 TI - Pharmacological evidence for a dual GABAergic regulation of growth hormone release in humans. AB - Effects of sodium valproate, which is believed to act via a gamma-aminobutyric acid mechanism, on basal and exercise-induced rise of growth hormone release have been tested in eighteen healthy volunteers. The exercise test consisted of using a stationary bicycle ergometer at 450 kg/min for 20 min. 600 mg per os of the drug resulted in a significant enhancement in plasma hormonal concentrations, whereas no effects were induced by placebo (p less than 0.005). Conversely, the growth hormone rise stimulated by exercise was markedly inhibited by sodium valproate (p less than 0.001 and p less than 0.01 at time 20, 40 and 60 min respectively). The results of this study are consistent with the hypothesis that a dual GABAergic control of growth hormone secretion is present in man. PMID- 3091976 TI - Influence of in vitro plating density on rat granulosa cell responsiveness to follicle-stimulating hormone. AB - The effects of cell plating density on granulosa cell sensitivity to follicle stimulating hormone (FSH) were investigated, using a serum-free culture of cells obtained from immature, estrogen-treated rats. The cells were incubated at densities of 0.25 to 5 X 10(5) cells/dish with increasing concentrations of FSH for 2 days, and medium estrogen and progestin accumulation were measured by radioimmunoassay. Per-cell estrogen and progestin production rose with increasing FSH concentration and cell density up to 2 X 10(5) cells/dish. At a higher density (5 X 10(5)/dish), per-cell estrogen production fell; progestin production remained constant, although the major progestin produced was no longer progesterone, but rather its metabolite, 20 alpha-hydroxy-progesterone. The effects of changing cell density could not be accounted for by medium steroids or cytotoxic substances. It is concluded that in vitro plating density can markedly affect granulosa cell sensitivity to FSH. In vivo, changing intrafollicular cell densities may thus affect the ability of the whole cell complement to respond to gonadotropin. PMID- 3091977 TI - Effect of murine schistosomiasis on hepatic cytochrome P-450 and microsomal protein. AB - Experimental hepatic schistosomiasis was produced in CBA mice using a local strain of S. mansoni. A comparative study of the hepatic concentrations of cytochrome P-450 and microsomal protein in the control and infected animals was carried out. S. mansoni infection significantly (P less than 0.05) reduced the liver cytochrome P-450 and microsomal protein. This suggests impairment of drug metabolism in the liver of infected animals. The study calls attention to the possible clinical and pharmacokinetic implications of the late severe S. mansoni infection of the liver in man. PMID- 3091978 TI - Cost-effectiveness of introducing a third-generation test for HBsAg in Danish blood donors. AB - Owing to the low incidence of hepatitis B in Denmark, screening of blood donors for HBsAg has mostly been done by immunoelectroosmophoresis (IEOP). The purpose of the present study was to carry out a cost-effectiveness analysis prior to the introduction of a third-generation test for HBsAg in Danish blood donors. The analysis was performed on data from a subsequent screening of 48 750 blood units by radioimmunoassay (RIA) 3 weeks after donation. The RIA-pos., IEOP-neg. blood donors identified in the study were evaluated by a follow-up examination, and the recipients of RIA-pos., IEOP-neg. blood units were monitored for up to 9 months as to the development of acute hepatitis B. The study shows that the estimated cost for each prevented case of transfusion-associated hepatitis B in Denmark is US$ 1100 when screening donors not previously tested by a third-generation technique, and US$ 240 000 when screening donors tested before by this technique. PMID- 3091979 TI - Liver morphology in marmosets infected with epidemic non-A, non-B hepatitis in India. AB - In this study the morphological changes in the livers of marmosets inoculated with stool extracts from epidemic non-A, non-B hepatitis patients in India were examined. The histologic changes of epidemic non-A, non-B hepatitis in marmosets consisted mainly of round cell infiltration in the portal tracts, spotty liver cell necrosis, sinusoidal lymphocyte infiltration, and Kupffer cell mobilization. By electron microscopy, liver cells from infected marmosets showed cisternal dilation of the endoplasmic reticulum, irregularly-shaped nucleus, and disorganization of the mitochondrial cristae. In some areas interaction of lymphocytes with hepatocytes was observed. Similar observations have been made in type B hepatitis infection, presumably due to liver cell damage mediated by immune mechanisms. The result of our study is also compatible with the interpretation that the liver cell damage in this experimental model may be mediated by immune mechanisms. PMID- 3091980 TI - Managing the risks of obstetrical nursing. PMID- 3091981 TI - Liability for the actions of others. PMID- 3091982 TI - Phases in the caring relationship: from adversary to ally to coordinator. PMID- 3091983 TI - The stress of medical management of pregnant diabetics. PMID- 3091984 TI - Diabetes and the school-aged child. PMID- 3091985 TI - Nipple stimulation-contraction stress test for the high-risk patient. PMID- 3091986 TI - Pediatric tours of hospitals--positive or negative? PMID- 3091987 TI - Family planning: beyond contraception. PMID- 3091988 TI - Epidural morphine for analgesia following a cesarean. PMID- 3091989 TI - Written reinforcement for teaching. PMID- 3091990 TI - [Diagnostic significance of electrocardiography and myocardial scintigraphy with 99m Tc-Sn-pyrophosphate and 99m Tc-Sn-phosphone in patients with stenocardia]. AB - Altogether 123 angina patients were examined using electrocardiography and scintigraphy of the myocardium with two 99m Tc radiopharmaceutical complexes: pyrophosphate and phosphone. A comparative analysis of the results obtained with different methods of investigation before and after an attack of angina pectoris was made. The authors have shown some peculiarities of radionuclide distribution in the myocardium and the diagnostic value of each method of investigation in patients with different clinical forms of angina pectoris. PMID- 3091991 TI - Pure red-cell aplasia in patients with chronic lymphocytic leukemia. AB - Four cases of pure red-cell aplasia (PRCA) in association with chronic lymphocytic leukemia (CLL) are summarized. In addition, all reported cases of CLL PRCA (27, including our 4 cases) are reviewed to consolidate their clinical features and compare them with those of 26 patients with CLL who were anemic (Stage III) and 52 who were not anemic (Stages O-II). The incidence of PRCA in our patients with CLL is about 6%. Eighty-seven percent of patients with PRCA had B-lymphocyte (B-cell) CLL and 13% had T-lymphocyte (T-cell) CLL. In 4 of 17 patients PRCA was the presenting feature, and in 13 of 17 it developed in patients previously diagnosed as having CLL. In the latter group, the average time from the diagnosis of CLL to the development of PRCA was 50.2 months (range, 1 to 96). The average age at presentation with PRCA was 61.6 years (range, 37 to 79), and the male to female ratio was 1.6 to 3:1. Eighty-one percent had splenomegaly and 65% had lymphadenopathy. The average hematocrit was 17 +/- 3.6% with zero reticulocyte count, and the lymphocyte count was 134 X 10(3)/microliter. Normoblasts were absent in the marrow and lymphocytes constituted 50 to 100% of the marrow cells. In patients with B-cell CLL and those with T-cell CLL, the T cells were found to inhibit the growth of the marrow erythroid progenitors in in vitro cultures. These abnormal T cells (Tr cells) possessed IgG Fc receptors on their surface, which may be responsible for induction of PRCA in these patients. Continued administration of cyclophosphamide and prednisone in moderate doses appears to induce remission from PRCA, but not until the leukemic mass and abnormal Tr cells are markedly reduced. Daily or alternate-day cyclophosphamide administration in small to moderate doses seems to be essential to maintain remission. PMID- 3091992 TI - Utilization of methionine and N-acetyl-L-cysteine during long-term parenteral nutrition in the growing rat. AB - Utilization of methionine and N-acetyl-L-cysteine as a source of cysteine was tested in growing rats receiving total parenteral nutrition for four weeks. The three solutions tested were isonitrogenous and isocaloric. One of the solutions contained an adequate amount of L-methionine, in the other two, two thirds of the L-methionine was substituted by a corresponding amount of either glycine or N acetyl-L-cysteine. Weight gain and N-balance were similar under the infusion with either the adequate amount of L-methionine or the N-acetyl-L-cysteine substituted. The solution in which two thirds of the L-methionine was replaced by glycine yielded only half of the weight gain and correspondingly reduced values for N-balance. The daily urinary excretion rate for N-acetyl-L-cysteine was 4.6% of the infused amount. Urinary excretion rates of the other amino acids and the plasma amino acid pattern was affected differently by the three solutions. The results indicate that cysteine is more rapidly available from N-acetyl-L-cysteine than from L-methionine when administered intravenously. PMID- 3091993 TI - Accumulation of DNA damages in aging Paramecium tetraurelia. AB - Paramecium tetraurelia cells of ages 4, 15, and 27 days were labeled with [14C] thymidine. In addition, cells were grown clonally for 27 days (108 generations) and labeled with [14C]-thymidine in the presence of 0.5 or 7.5 micrograms/ml of mitomycin-C (MMC) or no MMC. These cells were gently deposited on a filter membrane, which impedes the passage of DNA strands. The cells were then lysed with detergents and the cellular components washed through the filters, leaving double-stranded DNA intact on the surface. Proteinase K was used to remove histone or DNA-bound proteins. The DNA was then eluted under alkaline conditions, which denatures double-stranded DNA and converts apurinic/apyrimidinic sites into single-strand breaks. The results obtained with the cells of ages 4, 15, and 27 days (16, 60, and 108 generations, respectively) indicate that as Paramecium tetraurelia ages during asexual reproduction, apurinic/apyrimidinic lesions, strand breaks or single-strand gaps accumulate. This accumulation may be the basic mechanism of aging in such cells. In the MMC-treated cells of 27 days (108 generations), the MMC reduced elution of DNA fragments more at the higher than at the lower pH's used; random MMC cross-links should occur more often in longer strands than in shorter strands. The reductions in elution preferentially at higher pH, at which longer single strands would be eluted, confirmed the pH versus-length relationship for Paramecium DNA eluted under our conditions. PMID- 3091995 TI - Interaction of lectins from gonads and haemolymph of the sea hare Aplysia with bacteria. AB - Gonads and haemolymph of two Mediterranean species of Aplysia (A. depilans and A. fasciata) contain lectins. A. depilans gonad lectin is specific for D galacturonic acid and D-galactosides, while its haemolymph agglutinin binds N acetylated sugars. A. fasciata gonad lectin is also specific for D-galacturonic acid, but its haemolymph haemagglutinin exhibits heterogenic specificity. Both Aplysia gonad lectin and haemolymph agglutinins interact with bacteria, including certain Escherichia coli strains, Bacillus subtilis, Pseudomonas aeruginosa strains and marine bacteria such as the light producing Vibrio harveyi and Photobacterium leiognathi, as well as marine bacteria cultured from the close environment of Aplysia. PMID- 3091994 TI - Autoregulation of the nar operon encoding nitrate reductase in Escherichia coli. AB - Nitrate reductase is demonstrated to exert an autogenous control on its own synthesis. This effect requires the participation of the molybdenum cofactor. Use of strains in which the control region of the nar operon is mutated reveals two loci in this region: one, affected in strain LCB94, is common to both autoregulation and induction by nitrate while the other, mutated in strain LCB188, is specific for the induction by nitrate. It is proposed that the autogenous control prevents the unnecessary accumulation of the nitrate reductase subunits in the cytoplasm. PMID- 3091996 TI - Dissection of the role of macrophages in triggering T lymphocytes for interleukin 2 production by monoclonal antibody OKT3. AB - Unfractionated human peripheral blood mononuclear cells produce a small amount of interleukin 2 (IL 2) by stimulation with a monoclonal anti-T3 antibody (OKT3) in vitro. The IL 2 production could be greatly augmented by the addition of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). In the presence of TPA, the T cell enriched fraction deprived of macrophages did not produce IL 2, but the T cells pulse-incubated with OKT3 and reconstituted with macrophages efficiently produced IL 2 in subsequent culture in the presence of TPA as did T cells reconstituted with OKT3-pulse-incubated macrophages. The stimulating effect of OKT3 in the presence of macrophages was inhibited dose-dependently by the addition of immunoglobulins, particularly by mouse IgG2a which is the same isotype as that of the OKT3 antibody, showing that it inhibits by blocking the binding of OKT3 to Fc receptors on macrophages. The same extent of IL 2 production was induced in T cells when paraformaldehyde-fixed macrophages were substituted for intact macrophages. Remarkable IL 2 production was also induced by OKT3 when latex beads coated with rabbit anti-mouse IgG2a antibody and TPA were added to the culture. It was confirmed that the production induced by these stimulations was due to an increase of IL 2 mRNA. These results show that effective signals for IL 2 production are generated by efficient crosslinking of T3 molecules which results from multi-interaction of T3 molecules on the T cell membrane and anti-T3 antibody molecules on macrophage membrane or on the surface of the latex particle. PMID- 3091997 TI - Milk and arteriosclerosis. AB - Milk consumption is related to arteriosclerosis. Recent landmark studies confirm a previously suspected close correlation between milk intake and arteriosclerotic heart disease. Support is therefore provided for a recently proposed novel hypothesis that arteriosclerosis is a chronic infectious disease caused by blue green bacteria and that milk is a carrier vehicle for these contaminant organisms. A revisionist view of diet and milk in the causation of arteriosclerosis is developed. Previous hypotheses relating milk consumption to arteriosclerosis and advances in pasteurization techniques are discussed and integrated with this infection theory. PMID- 3091998 TI - Drugs for epilepsy. PMID- 3091999 TI - Leukemia versus lymphoma in children: a worthless question? PMID- 3092000 TI - Recognizing and classifying epileptic seizures and epileptic syndromes. AB - The appropriate diagnosis of the patient with epilepsy is first dependent on a determination of the type of seizure. When the type of seizure has been determined, consideration must be given to the nature of the epileptic syndrome, including concerns regarding the etiology of the attacks. The gradual evolution of the various classification schemes of epileptic seizures and epileptic syndromes complicates the task of the physician but also affords evidence of the dynamism extant in clinical epilepsy research. Intensive monitoring will assist not only in the diagnosis of the individual patient but also in the long-term re evaluation and revision of the empirical classifications. PMID- 3092001 TI - The electroencephalogram in the evaluation of the patient with epilepsy. AB - The authors describe the use of the electroencephalogram (EEG) in the diagnosis of patients with epilepsy, with specific reference to various seizures types and to commonly seen electrographic abnormalities. Also reviewed are normal variants that are sometimes erroneously thought to be epileptic in nature. The use of special studies, including invasive electrographic recording, is briefly discussed. PMID- 3092002 TI - Seizures as a manifestation of systemic disease. AB - Although many systemic disorders involve the nervous system and may cause seizures, certain clinical features are unique to some illnesses. This article reviews seizures associated with collagen vascular disorders, vasculitidis, fluid and electrolyte disturbances, endocrine diseases, porphyrias, renal and hepatic disorders, and drugs. Emphasized are features associated with each systemic disorder that may aid in diagnosis and therapy. PMID- 3092003 TI - Use of ethosuximide and valproate in the treatment of epilepsy. AB - Ethosuximide is the drug of first choice in absence seizures. Idiosyncratic side effects are rare. Valproate is effective against absence, generalized tonic colonic, and partial seizures. It is the drug of choice in photosensitive seizures. Valproate is, on the whole, free from unpleasant side effects, but fatal hepatotoxicity and hyperamnionemia have been reported very rarely. PMID- 3092004 TI - Status epilepticus. AB - Treatment of SE has improved considerably during the last decade. Mortality from SE itself should be minimal if effective treatment is delivered rapidly. Currently, the risk of complications from appropriate treatment is less than the risk of injury from additional seizures. Loading with phenytoin, 20 mg per kg, using benzodiazepam if needed, is the current treatment of choice. If seizures persist, phenobarbital 10 to 20 mg per kg should be used. If convulsive SE continues for more than 1 hour, pentobarbital coma is necessary. PMID- 3092005 TI - Neuroimaging. AB - The role of neuroimaging procedures, including new techniques, such as positron emission tomography and magnetic resonance imaging in the evaluation of seizures, is discussed. PMID- 3092006 TI - Annual summary 1984. Reported morbidity and mortality in the United States. PMID- 3092007 TI - Use of death certificate for surveillance of work-related illnesses--New Hampshire. PMID- 3092008 TI - Thrombotic thrombocytopenic purpura associated with Escherichia coli O157:H7- Washington. PMID- 3092009 TI - Aseptic meningitis among kidney transplant recipients receiving a newly marketed murine monoclonal antibody preparation. PMID- 3092010 TI - Brazilian purpuric fever: Haemophilus aegyptius bacteremia complicating purulent conjunctivitis. PMID- 3092011 TI - Rabies in a javelina--Arizona. PMID- 3092012 TI - Declining anemia prevalence among children enrolled in public nutrition and health programs--selected states, 1975-1985. PMID- 3092013 TI - Outbreak of malaria imported from Kenya. PMID- 3092015 TI - Maternal deaths associated with barbiturate anesthetics--New York City. PMID- 3092016 TI - Tuberculosis and acquired immunodeficiency syndrome--Florida. PMID- 3092014 TI - New recommended schedule for active immunization of normal infants and children. PMID- 3092017 TI - The effectiveness of school health education. PMID- 3092018 TI - Toxigenic Vibrio cholerae 01 infections--Louisiana and Florida. PMID- 3092019 TI - Leading work-related diseases and injuries. PMID- 3092020 TI - Misclassification of maternal deaths--Washington State. PMID- 3092021 TI - [Nutritional management of surgical patients: current status and future]. PMID- 3092022 TI - [The effect of RT1 subregion differences on pancreatic islet allograft survival in the rat]. PMID- 3092023 TI - [Experimental and clinical studies on chemosensitivity tests of anticancer agents by human tumor clonogenic assay]. AB - In vitro chemosensitivity tests of anticancer agents for 119 fresh human tumors were performed by the human tumor clonogenic assay (HTCA) technique and the following results were obtained. Colony growth (greater than or equal to 5 colonies/dish) was observed in 35 of 50 gastric cancers (70.0%), 10 of 17 colon cancers (58.8%), 13 of 14 breast cancers (92.9%), two of six esophageal cancers (33.3%), three of six sarcomas (50.0%), three of 16 hematological malignancies (18.8%) and seven of 10 other tumors (70.0%). Colony growth rate differed according to the type of tumor. Fifty four tumors formed adequate colony growth (greater than or equal to 30 colonies/dish) for the chemosensitivity test. Mitomycin C (MMC), 5-Fluorouracil (5-FU), 4-hydroperoxy cyclophosphamide (CPM), Adriamycin (ADM), Cis-dichlorodiammineplatinum (CDDP), and alpha-interferon (IFN alpha) were tested. The average positive rates of MMC, 5-FU, CPM, CDDP, and IFN alpha were 26.9, 21.6, 10.5, 26.9, 36.8, and 23.3% respectively for all the tumors tested. In gastric cancer, the positive rates of MMC and 5-FU were 24.0 and 21.6% respectively, whereas the rates were 33.3 and 33.3% in colon cancer and 18.2 and 16.7% in breast cancer respectively. Each tumor exhibited its own chemosensitivity rates against various anticancer agents. Eighteen of the results obtained were comparable to clinical responses. The true positive rate was 50.0% (2/4) and the true negative rate 92.9% (13/14). A statistically significant correlation was observed between the results of HTCA and clinical responses (chi 2 test, p less than 0.05). The combined effects of IFN-alpha and MMC were surveyed against 20 gastroenterological tumors. Nine tumors exhibited synergistic effect, though antagonistic effect was observed in three tumors. The effects of oxygen tension (2%, 5%, 20%) on colony growth were investigated. The greatest development of colonies occurred at an oxygen of five percent, which is considered to be physiological oxygen tension, and statistically significant increases of plating efficiencies at 5% O2 as compared to those at 20% O2 were observed (t-test, p less than 0.025). PMID- 3092024 TI - [Hepatic disorder during long-term intravenous hyperalimentation in adults]. AB - Hepatic disorder during long-term intravenous hyperalimentation (IVH) in adults was studied. Fifty-one patients (30 males and 21 females) in whom IVH was performed for more than 60 days at Tenri Hospital from 1975 to 1984, were divided into 3 groups by change of indices which showed hepatic cellular injury (CII) and bile stasis (BSI). Namely, type I patients (33 cases) showed transient abnormality of indices, type II patients (14 cases) has continuous abnormal indices during IVH and type III patients (4 cases) were lethal due to hepatic failure. There were no differences in clinical feature among 3 groups. Incidence of metabolic complications during IVH in type II was significantly higher than in type I (p less than 0.05). All patients of type III were complicated by severe infectious diseases. Chief histological findings from 13 specimens (6 biopsies and 7 autopsies) were fatty degeneration of hepatocytes and fibrosis in the portal area with proliferation of bile ducts. Change of the portal area had closer relationship to the clinical severity of hepatic disorder than change of hepatocytes. BSI was more important than CII in inspection of clinical course and estimation of prognosis on hepatic disorder during IVH. PMID- 3092025 TI - [Postoperative nutritional assessment in gastric and colorectal cancer]. AB - From the 200 malnutritional cancer patients, we had obtained, so called, prognostic nutritional index (PNI): PNI = 10 X Alb. + 0.005 Lymph. C., where Alb. is serum albumin level (g/dl) and Lymph. C. is total lymphocytes count of peripheral blood level. This index, as we had reported, shows linear predictive model correlating the risk of operative complication, mortality or both with nutritional status. In this study, we report on the utility of the PNI as a nutritional index (NI) for postoperative patients. The subjects of this study were 22 gastric cancer patients (G group), performed total gastrectomy or proximal gastrectomy, and 18 colorectal cancer patients (C group), underwent colectomy or rectal resection and anastomosis but amputation. All these cases underwent nutritional support by TPN postoperatively. The values of NI of both groups were the lowest at the first postoperative day, and increased gradually to the seventh postoperative day. And the value of C group was higher than that of G group throughout the TPN period: From the first postoperative day to the 14th day. These results reflected the result obtained from the estimation of nitrogen balance, urinary 3-methylhistidine excretion and serum rapid turnover protein (transferrin, prealbumin and retinol binding protein). These results suggest that the NI is useful to estimate the improvement of the postoperative nutritional status. PMID- 3092026 TI - Effect of solubilization on the distinct binding properties of muscarine receptors from rabbit hippocampus and brainstem. AB - The binding of carbachol, quinuclidinyl benzilate, pirenzepine, and scopolamine to muscarine receptors from the rabbit hippocampus and brainstem was examined in membranes and in digitonin solution, in order to determine whether the dispersion of receptor molecules altered the distinct ligand-binding profiles of the receptors of these tissues. The modification of receptor-effector complexes showing high affinity for carbachol in membranes, with guanyl 5'-yl imidodiphosphate (GppNHp), N-ethyl-maleimide (NEM), and ethylenediaminetetraacetate (EDTA), did not remove receptor heterogeneity. In addition to receptor heterogeneity, GppNHp-sensitive high affinity agonist binding to membranes was NEM sensitive in the brainstem but NEM insensitive in the hippocampus. Solubilization with digitonin in the presence of Mn2+ ions yielded GppNHp-sensitive, high affinity agonist-binding complexes from the brainstem but not the hippocampus. More extensive dissociation was achieved with solubilization in EDTA and NEM, and resulted in receptor populations which showed markedly lower and slightly different affinities for carbachol. However, the selectivities and affinities for three antagonists were little changed in solution from those found in membranes. These results support the view that there are differences in muscarine receptors as well as different receptor complexes with guanine nucleotide-binding regulatory proteins. The selective binding of carbachol appears largely dependent upon the association of receptors with other molecules, including effector molecules, whereas antagonists appear to recognize receptors irrespective of associated molecules. PMID- 3092027 TI - The cytochrome P-450 monooxygenase system of rabbit lung enzyme components, activities, and induction in the nonciliated bronchiolar epithelial (Clara) cell, alveolar type II cell, and alveolar macrophage. AB - Enzyme components and activities of the cytochrome P-450 monooxygenase system in microsomal preparations from the Clara cell, alveolar type II cell, and alveolar macrophage fractions isolated from lungs of untreated rabbits and rabbits treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin were examined. Results are compared to those obtained with microsomal preparations from whole lung. Concentrations of cytochrome P-450 isozymes 2 and 5 and NADPH-cytochrome P-450 reductase activities were higher in preparations from Clara cell fractions than in preparations from type II cell fractions or whole lung. For the most part, however, differences among these preparations were 2-fold or less. Microsomal preparations from the macrophage fraction contained low or undetectable levels of cytochrome P-450 isozymes but relatively high levels of cytochrome P-450 reductase activity. The concentration of cytochrome P-450 isozyme 6, in contrast to those of isozymes 2 and 5, was found to be highest in microsomal preparations from whole lung. Treatment of rabbits with 2,3,7,8-tetrachlorodibenzo-p-dioxin increased the concentrations of isozyme 6 in preparations from the Clara and type II cell fractions and from whole lung about 20-fold. In contrast, the content of isozyme 6 in preparations from the macrophage fraction increased greater than 90-fold. In all cases, induction of isozyme 6 resulted in substantial increases in the O deethylation of 7-ethoxyresorufin and only minor increases in the hydroxylation of benzo(a)pyrene. Activities per unit of isozyme 6, following induction, were similar in all preparations, and we estimate that less than 20% of the potential activity of isozyme 6 is expressed with benzo(a)pyrene and greater than 40% with 7-ethoxyresorufin. These similarities exist in spite of significant differences among the preparations from different fractions in the ratios of isozyme 6 to NADPH-cytochrome P-450 reductase. PMID- 3092028 TI - Isolation and partial characterization of a fragment corresponding to the dimeric form of the CH2 domain of rabbit IgG. AB - A fragment corresponding to the intact dimeric form of the CH2 domain of rabbit IgG, including the hinge region disulfide linkage, was obtained by plasmin digestion of crystalline Fc derived from IgG by the action of papain. Identification and assessment of purity of the fragment was established by SDS PAGE, amino acid composition analysis, N-terminus sequence and C-terminus amino acid analysis and SDS-urea-PAGE of the reduced fragment. The fragment retains serologic reactivity with anti-Fc specific antisera. Comparison of deglycosylation by endoglycosidase F indicates a more open special relationship between the two CH2 domains in the fragment than in Fc. PMID- 3092029 TI - The role of the VL- and VH-segments in the preferential reassociation of immunoglobulin subunits. AB - Competitive reassociation experiments, in which equimolar amounts of two different L-chains were allowed to compete for a limiting amount of H-chain, were performed to assess the role of the V kappa- and J kappa-segments on the ability of an L-chain to compete. Using H- and L-chains from the murine anti phosphorylcholine (PC) myelomas, TEPC15, MOPC167 and MCPC603, and a series of V kappa 21 L-chains, it was found that the V kappa 21 L-chains competed uniformly better than the anti-PC L-chains, when the anti-PC H-chains were used, despite any differences in the J-segments of the competing L-chains. In addition, when the anti-PC L-chains, which all employ identical J kappa-segments but very diverse V kappa-segments, were in competition against each other, a hierarchy of competitive ability existed which was independent of whether the chains were autologous or heterologous and independent of antigen binding activity. Competitive reassociation experiments between the V kappa 21 and anti-PC L-chains were also performed using the heterologous anti-lysozyme monoclonal HyHEL-10 H chain or the anti-galactan J539 H-chain, and it was found that the relative competitive ability of the V kappa 21 L-chains with respect to the anti-PC L chains was dependent on which H-chain was employed. The results suggested that the main factor favouring preferential reassociation by any particular L-chain was the V kappa-segment and that the effects of the J kappa-segment could not be observed where a high degree of diversity in the V-segments existed. Furthermore, while the results implied that specific pairs of VH- and VL-domains had a higher affinity for each other, this was not a necessary criterion in the formation of autologous pairs of H- and L-chains as demonstrated by the preferential heterologous reassociation of the V kappa 21 L-chains over the autologous anti-PC L-chains. These results were consistent with the independent, random rearrangement of immunoglobulin H- and L-chain V-domain gene segments and predict that the hypothetical repertoire of antibodies is not limited by the selection of specific pairs of high-affinity VH-VL domains. PMID- 3092030 TI - The synthesis and expression of HLA-A and -B antigens in Xenopus laevis oocytes. AB - Purified mRNA's encoding the HLA-A and -B antigen heavy chains or beta 2 microglobulin were prepared from human B lymphoid cells by positive hybridization selection procedures. The role of chain association in the biosynthesis and intracellular transport of HLA-A and -B antigens was investigated by injecting these mRNA species into Xenopus laevis oocytes and following the fates of the translated products by immunoprecipitation. When mRNA encoding beta 2 microglobulin from the B lymphoblastoid cell line MST was coinjected with mRNA encoding the HLA-A and -B antigen heavy chains from the Burkitt lymphoma cell line Daudi, fully assembled class I antigens were detected using the monoclonal antibody W6/32. This result suggested that there may be no defect in the mRNA encoding Daudi HLA-A and -B antigen heavy chains. When the state of maturity of the N-linked glycan units on these class I antigen heavy chains was assessed, they were found to have undergone some processing. In contrast, when mRNA encoding immunoglobulin M (IgM) was injected into oocytes, the glycan units of the IgM heavy chains were found to be in the unprocessed (high mannose) form. This result shows that Xenopus oocytes can process some eukaryotic glycoproteins of exogenous origin. PMID- 3092031 TI - The stoichiometry of J chain in human secretory dimeric IgA. AB - Dimeric human secretory IgA was completely reduced with mercaptoethanol and alkylated with [14C]iodoacetamide. The component polypeptide chains were separated by high performance gel filtration in 5 M guanidine HCl into two fractions: one containing secretory component (SC) + heavy (H) chains; and the second containing light (L) + J chains. L and J chains were subsequently separated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS) or in alkaline urea. Calculations of the J chain stoichiometry in the dimeric secretory IgA (S-IgA) molecule were based on: the measurement of the ratio of radioactivities of SC + H chain and L + J chain-fractions or L chain- and J chain fractions; the known stoichiometry of SC, H and L chains; and the known number of half-cystine residues in the component polypeptide chains of S-IgA molecule. The data demonstrated that one molecule of dimeric S-IgA contains approx. one J chain. PMID- 3092032 TI - Detection of 4-O-acetyl-N-glycolylneuraminyl lactosylceramide as one of tumor associated antigens in human colon cancer tissues by specific antibody. AB - Antibody to 4-O-acetyl-N-glycolylneuraminyl lactosylceramide [GM3(Neu4AcGc)] was prepared by immunizing chicken with the glycosphingolipid antigen. The specific antibody was purified by affinity chromatography columns of Octyl-Sepharose linked to the homologous immunogen and its deacetylated analogue [N glycolylneuraminyl lactosylceramide, GM3(NeuGc)], respectively. The specificity of the purified antibody was confirmed by enzyme-linked immunosorbent assay (ELISA) and inhibition of equine erythrocyte hemagglutination using authentic glycosphingolipids as antigens. The results indicated that the antibody recognized both 4-O-acetyl and N-glycolyl groups of terminal sialic acid residue as the immunodeterminants. The purified specific antibody was applied in the confirmation of the presence of GM3(Neu4AcGc) in ganglioside fractions of human colon cancer tissues, which were suspected to have this antigen by studies of alkaline, periodate or neuraminidase treatment [Higashi et al. (1985) Cancer Res. 45, 3796-3802.], by thin-layer chromatography (TLC)-immunostaining technique. PMID- 3092033 TI - Human IgM antibodies do not activate guinea-pig complement after interaction with soluble antigen. AB - Activation of guinea-pig complement by human IgM antibodies after interaction with a particulate antigen is well established. Human IgM antibodies directed against meningococcal group-C capsular polysaccharide, however, were not able to fix guinea-pig complement in a classical complement fixation test with soluble antigen. In the same test, human complement was readily activated by these antibodies. This inability of human IgM antibodies to activate guinea-pig complement after interaction with soluble antigen was confirmed in other antigen systems. In contrast, efficient activation of both human and guinea-pig complement was found with the same antigen in a particulate form. PMID- 3092034 TI - [The neglected child]. AB - Although the figure for unreported cases of neglected children is much higher than that of physical ill-treatment of children, neglect has rarely received attention, in most cases only when traces of physical ill-treatment were proven at the same time. Symptomatic are in the first place intense emaciation as well as dry puckered, scaly and extremely dirty skin, lack of subcutaneous fatty tissue and of Bichat's fat pad, matted hair, aged face, sunken eyes, and eczema from urine with ulcerations in the buttock and thigh regions. In addition one finds signs of localized hypothermia or rickets. My own observations cover 80 cases in which neglect and malnutrition have caused the death of the children involved. All the children had been living in extremely bad social conditions. The backgrounds of the children's mothers were also socially poor. Most of the mothers were too young to fulfill their duties. The fathers, where known, were alcoholics, unwilling to work and seldom cared for their family. They too were often too young to cope with their role as father. In this day and age, which has provided us with a much better understanding of the importance of the early development of children for their later social adaptation, mothers with all their problems and difficulties should not be left on their own. Mothering behaviour is not necessarily programmed with the birth of a child. Mothering duties must be learned as early as possible. This process should begin during pregnancy at the latest. A few proposals will be made. PMID- 3092035 TI - [Radiologic diagnosis of the battered child syndrome]. AB - The imaging modalities play a key role in the investigation and documentation of the battered child syndrome. The primary diagnostic imaging study in suspected child abuse is either a bone scan and x-ray series or a complete radiographic skeletal survey by x-ray series in babies and infants. In expected intracranial injuries, a CT scan of the head is mandatory; ultrasound has to be performed in order to exclude visceral lesions. The conventional radiographic examination permits us to identify the appearance of the injury (periosteal bleeding and ossification, metaphyseal fragmentation, fracture and epiphysiolysis) as well as the mechanism of the lesion: direct blow, twisting or traction of a limb, compression or shaking. In addition the age of the lesion can be derived from typical healing processes of the skeleton. Furthermore, non accidental skeletal malformations can be detected and may allow the exclusion of child abuse. PMID- 3092036 TI - [Retinopathy of prematurity]. AB - The new international classification of the different stages of RLF is presented. The incidence of ROP varies between 10 and 80/100,000 live births, and 7 and 40% of all prematures. Recent data from Switzerland indicate that 12% of the 7-16 years old scholars in schools for visually disabled children have advanced stages of ROP (RLF). 27% of the totally blind scholars have RLF. The main risk factors are immaturity of retinal vascularization and oxygen. Other postulated risk factors like f.e. elevated or fluctuating pCO2 are discussed. Indications and a time schedule for ophthalmological examination are suggested. Prophylactic measures as f.e. Vitamin E administration are briefly mentioned. Finally, ophthalmological treatment is critically evaluated. An efficiency of coagulation has not yet been proven. An uncomplicated retinal detachement can be treated with conventional retinal surgery if it does not regress spontaneously during the course of active ROP. Chances to gain visual benefit from extreme vitreo-retinal surgery of endstage RLF with total retinal detachement cannot yet fully be estimated but seem to be very low. PMID- 3092037 TI - O-alkylation in DNA does not correlate with the formation of chromosome breakage events in D. melanogaster. AB - Postmeiotic cell stages of repair-proficient ring-X (RX) males were treated with methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), diethylnitrosamine (DEN) or ethylnitrosourea (ENU) and then mated to either repair-defective (mei 9L1) or to repair-competent females (mei-9+). Absence of the mei-9+ function resulted in a hypermutability effect to all alkylating agents (AAs) when they were assayed for their ability to induce chromosomal aberrations (chromosome loss; CL), irrespective of marked differences in distribution of DNA adducts brought about by these AAs. This picture is different from that described previously for the induction of point mutations (Vogel et al., 1985a). There, evidence was presented indicating that reduction in DNA excision repair does not affect point mutation induction (recessive lethals) by those AAs most efficient in ring-oxygen alkylation such as ENU, DEN, N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), and isopropyl methanesulfonate (iPMS): the order of hypermutability of AAs with mei-9L relative to mei-9+ was MMS greater than MNU greater than DMN = EMS greater than iPMS = ENU = DEN = ENNG. When the percentage of lethal mutations induced in mei-9L1 females were plotted against those determined for mei-9+ females, straight lines of following slopes were obtained: MMS = 7.6, MNU = 5.4, DMN = 2.4, EMS = 2.4, and iPMS = ENU = DEN = ENNG = 1. Those findings, together with the recent observation that AAs do not split into two groups when assayed for their ability to cause CL, point to the involvement of different DNA alkylation products in ENU- and DEN-induced chromosome loss vs. that of point mutations. It is concluded that with ENU and DEN chromosomal loss results from N alkylation products whereas point mutations (SLRL) are the consequence of interactions with oxygen-sites in DNA. Thus, as a consequence of a very dominating role of O-ethylguanine (and possibly O4-alkylation of thymine), N alkylation in DNA does not contribute measurably to mutation induction in the case of ENU-type mutagens while O-alkylation, very clearly, does not show a positive correlation with the formation of chromosome breakage events in Drosophila. Conversely, it appeared that with MMS-type mutagens (MMS; dimethyl sulfate, DMS; trimethyl phosphate, TMP), alkylation products such as 7 methylguanine and 3-methyladenine, if unrepaired or misrepaired, are potentially mutagenic lesions causing both mutations and chromosomal aberrations. PMID- 3092038 TI - Influence of incorporated 5-bromodeoxyuridine on the frequencies of spontaneous and induced sister-chromatid exchanges, detected by immunological methods. AB - We have utilized monoclonal antibody against BrdUrd to detect sister-chromatid exchanges in CHO cells. This technique allows detection of SCEs at very low levels of BrdUrd incorporation. At incorporation level of 0.5%, a frequency of about 2 SCEs/cell/cycle was found. In a UV-sensitive mutant (43-3B) which has an increased spontaneous frequency of SCEs, it is found that this increase is due to incorporated BrdUrd. In MMS- and MMC-treated cells, an influence of BrdUrd on the frequencies of induced SCEs was found only when high concentrations of mutagens were employed. PMID- 3092039 TI - Evaluation of the genotoxic activity of some mycotoxins using Escherichia coli in the SOS spot test. PMID- 3092042 TI - High-risk infants and families offered transitional care. PMID- 3092040 TI - The Escherichia coli K-12 SOS chromotest agar spot test for simple, rapid detection of genotoxic agents. AB - The Escherichia coli K-12 SOS chromotest is a colorimetric (beta-galactosidase induction) system for detecting genotoxic chemicals as agents which induce filamentation in response to DNA damage. The chromotest was modified from a liquid suspension assay to a simple, convenient agar spot test, which was performed in the manner of a related colorimetric prophage induction assay (BIA). Chromotest agar dishes yielded optimal results after 16-18 h incubation, presumably because of the agar growth characteristics of tester strain PQ37. Of 44 tested chemicals, nitro aromatics, cytotoxic/antitumor agents, polycyclic hydrocarbons and aflatoxins showed good activity. Alkylating agents such as MNNG and MMS were active only at high concentrations. Compounds active in both the chromotest and BIA were active at 10-100-fold lower concentrations in the chromotest. The chromotest appeared to be less effective than the Salmonella Ames mutagenicity test in the detection of diverse classes of chemical carcinogens. The chromotest may be a useful alternative to the BIA in the study of particular classes of genotoxic compounds. PMID- 3092041 TI - Inhibition of ADP-ribosylation increases X-ray-induced chromosomal damage in mouse testis and bone-marrow cells in vivo. AB - The effect of 3-aminobenzamide (3AB) treatment on chromosomal radiosensitivity of mouse spermatogonial stem cells and bone-marrow cells was studied using various doses of X-rays. The results show that 3AB increases the induction of reciprocal translocations in slowly cycling spermatogonia as well as the frequency of chromosomal aberrations in actively dividing bone-marrow cells. The experiments indicate that both types of tissue are suitable to study the ability of inhibitors of ADP-ribosylation to modulate chromosome-breaking damage induced by ionizing radiation in vivo. PMID- 3092043 TI - Recommendations of DES Task Force. PMID- 3092044 TI - Facing the facts on adolescent pregnancy. PMID- 3092045 TI - The changing role of men in childbirth. PMID- 3092046 TI - Purification and partial characterization of the major antigen of Echinococcus granulosus (antigen 5) with monoclonal antibodies. AB - A monoclonal antibody specific for antigen 5 of Echinococcus granulosus was isolated and partially characterized. Purification of antigen 5 was accomplished by affinity chromatography using an immunoabsorbent prepared with this monoclonal antibody. Pure antigen 5 was identified by immunoelectrophoresis, double diffusion in agar gel, sodium dodecyl sulphate-polyacrylamide gel electrophoresis and immunoblotting. The pure antigen displayed the electrophoretic mobility typical of antigen 5 and gave a single precipitin band in double diffusion with both monoclonal antibody and rabbit anti-pH5PPT hydatid fraction serum. Two bands of 66 and 56 kDa could be detected in the pure antigen 5 after sodium dodecyl sulphate-polyacrylamide gel electrophoresis when performed in non-reducing conditions: both bands were reactive with the monoclonal antibody in immunoblotting. After reduction with 2-mercaptoethanol, antigen 5 displayed one band only, of 39 kDa. Antigen 5 purified by this procedure was found to retain reactivity with human sera from hydatid patients in a DD5 test. PMID- 3092047 TI - Effect of putrescine on the respiration of Trypanosoma brucei brucei. AB - When bloodstream forms of Trypanosoma brucei brucei were exposed to exogenous putrescine for 24 h during in vitro culture, the rate of O2 consumption increased significantly in a concentration-related and time-dependent manner. Trypanosomes cultured with 100 microM DL-alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, were depleted of intracellular putrescine, and the rate of O2 consumption decreased by more than 50%. This effect could be abrogated if 100 microM putrescine was also present. A similar pattern was observed in trypanosomes harvested from rats after 36 h of DFMO treatment. If such trypanosomes were placed in culture for 2 h with 100 microM putrescine, the rate of O2 consumption returned to that of controls. When an intraperitoneal injection of putrescine was given to infected rats 18 h after commencement of DFMO treatment, rates of O2 consumption in the trypanosomes were found to return to control values. The addition of putrescine, spermidine or Mg2+ did not affect rate of O2 consumption in enriched mitochondrial preparations. However, when putrescine was present throughout the preparation of mitochondrial fractions, there was an increase of 23% in O2 uptake, which was 23% higher than in the controls. Putrescine may modulate trypanosomal respiration by stabilizing mitochondrial membranes. PMID- 3092048 TI - DNA synthesis in Plasmodium berghei during asexual and sexual development. AB - DNA contents of individual stages of Plasmodium berghei were measured by direct microfluorometry after Feulgen-pararosaniline (SO2) staining. Sporozoites, intra erythrocytic ringforms and trophozoites (until at least 15 h after invasion) are haploid and non-synthesizing DNA. DNA is synthesized just before and during schizogony, which takes 4-6 h. Genome duplication and segregation are alternating events throughout this process. Mature micro- and macrogametocytes have DNA contents between the haploid and diploid value; most, if not all of the DNA in excess of the haploid value is synthesized during the last 5-10 h of maturation. During gametogenesis microgametocytes within 8-10 min synthesize DNA steadily and at a very high rate to more than the octoploid value while the DNA content of macrogametocytes remains constant. Fertilization in vitro takes place within 1 h after gamete formation. Within 2 h and coinciding with the onset of meiosis the zygote then synthesizes DNA up to almost the tetraploid value, after which synthesis stops during ookinete development. All the above mentioned processes of DNA synthesis are reversibly inhibited by aphidicolin (C50 from 3-13 microM). From the rate of DNA synthesis during microgametogenesis we calculated a minimum of 1300 origins of replication in the haploid genome of P. berghei. PMID- 3092049 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 36-1986. A 29-year-old woman with slowly progressive proximal muscle weakness. PMID- 3092050 TI - The relation of apolipoproteins A-I and B in children to parental myocardial infarction. AB - Clinical studies suggest that serum levels of apolipoproteins A-I and B may be more strongly related to coronary artery disease than are their respective lipoprotein-cholesterol fractions. Therefore, we assessed the association between levels of apolipoprotein B, apolipoprotein A-I, lipids, and lipoprotein cholesterols in children and the reported histories of myocardial infarction in their parents in a survey of 2416 black and white school-age children. As compared with children whose fathers did not report a myocardial infarction, those whose fathers reported having had an infarction (n = 139) had a lower mean level of apolipoprotein A-I (137 vs. 141 mg per deciliter; P = 0.04) and a lower ratio of low-density lipoprotein cholesterol to apolipoprotein B (1.08 vs. 1.11; P = 0.007), along with a higher ratio of apolipoprotein B to apolipoprotein A-I (0.64 vs. 0.61; P = 0.04). These associations existed independently of the children's race, sex, age, and history of obesity, smoking, alcohol intake, and use of oral contraceptives. Children whose mothers reported having had a myocardial infarction (n = 56) had no decrease in the ratio of low-density lipoprotein cholesterol to apolipoprotein B, but they tended to have an elevated ratio of apolipoprotein B to apolipoprotein A-I. In contrast, serum lipoprotein cholesterol fractions in children were not related to myocardial infarctions in either parent. These results provide further evidence that apolipoproteins are more strongly related to the risk of cardiovascular disease than are lipoprotein cholesterol fractions. PMID- 3092051 TI - Canada's health care system (2). PMID- 3092052 TI - The need for health care expenditures. PMID- 3092053 TI - Withdrawal reaction after long-term therapeutic use of benzodiazepines. AB - We conducted a double-blind, placebo-controlled trail in which 40 patients who had undergone long-term therapy with benzodiazepines were switched to placebo or to diazepam in a dose approximately equivalent to their usual dose of the benzodiazepine; the dose of diazepam was then tapered during an eight-week period. Patients were assessed clinically and psychologically and had weekly sessions of behavioral therapy. The subjects who received placebo had more symptoms, assessed their symptoms as more severe, and stopped taking the study drug at a higher rate than those receiving the tapering doses of diazepam. The subjects in the placebo group also had symptoms shortly after being switched to placebo, whereas those in the diazepam group had symptoms much later. Some withdrawal symptoms were distinct from those of anxiety (e.g., tinnitus, involuntary movement, and perceptual changes). Withdrawal symptoms occurred earlier in patients who had received short-acting benzodiazepines than in those who had received long-acting benzodiazepines. Symptoms gradually disappeared over a four-week period in both the placebo and the diazepam groups. Serial determination of plasma benzodiazepine concentrations was a useful way to assess compliance, treatment outcome, and relapse during withdrawal. We conclude that a clinically important, mild, but distinct withdrawal syndrome occurs after discontinuation of long-term therapeutic use of benzodiazepines. PMID- 3092055 TI - Characterization and properties of infant milk formulae with addition of enzymatically digested casein. PMID- 3092054 TI - Fragmentation of myofibrils, limited proteolysis and water holding capacity of meat. AB - Protein changes in ageing meat result in increased vulnerability of the myofibrils to fragmentation, caused possibly by limited proteolysis. It was investigated which groups of muscle proteases, if any, were involved and what was the relation between fragmentation and hydration of beef meat. In samples ranging in natural pH from 5.4 to 7.0 the least fragmentation after 3 days at 2 degrees C was at pH 6. This could suggest the role of both the cathepsins and neutral proteases. In samples aged in the presence of EDTA fragmentation was significantly lower than in the controls. This could indicate the role of Ca2+ activated neutral proteases, or support the hypothesis on the nonenzymatic mechanism involving Ca2+. The results of PAG electrophoresis could not have been due to the neutral proteases, as the 30,000 g X mol-1 component, resulting from the hydrolysis of troponin T, did not accumulate at pH 7 until the 9th day of ageing, but at pH 5.4 the intensity of this band increased markedly already after 3 days. There was no correlation between the fragmentation and the hydration of the aged meat after cooking. The addition of 0.001% of trypsin or 0.0005% of papain to minced meat did not cause after 9 days any increase in the contents of free amino acids and peptides or significant changes in the PAGE pattern as compared to those in the controls. However, the fragmentation and hydration of the raw meat was larger in the samples containing added enzymes. After cooking the hydration of the samples did not differ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092056 TI - Hydrolyzed casein as a source of bifidus factor. PMID- 3092057 TI - Problems of drug dependence, 1985. Proceedings of the 47th annual scientific meeting, The Committee on Problems of Drug Dependence, Inc. Baltimore, Maryland, June 1985. PMID- 3092058 TI - Endogenous opioid modulation of luteinizing hormone, prolactin, and estradiol in women: interactions with ethanol. PMID- 3092059 TI - Alcohol effects on LHRH-stimulated LH in female rhesus monkeys. PMID- 3092060 TI - Nalbuphine, pentazocine, and butorphanol interactions with tripelennamine in mice. PMID- 3092061 TI - Development of cigarette smoking in rhesus monkeys. PMID- 3092062 TI - Substitution and cross-tolerance profiles of phenmetrazine and diethylpropion in rats trained to detect the stimulus properties of cocaine. PMID- 3092063 TI - Human drug discrimination: d-amphetamine and other anorectics. PMID- 3092064 TI - Proposal regarding opioid anomalies: preliminary report. PMID- 3092065 TI - Behavioral contingencies and d-amphetamine effects on human aggressive and non aggressive responding. PMID- 3092066 TI - Involvement of the ventral tegmental dopamine system in opioid and psychomotor stimulant reinforcement. PMID- 3092067 TI - Acute chlordiazepoxide dependence in the rat: comparisons to chronic. PMID- 3092068 TI - EEG, physiologic and behavioral effects of ethanol administration. PMID- 3092069 TI - Neurochemical and pharmacologic investigations of punished behavior. PMID- 3092070 TI - Morphine potentiates feeding via the opiate reinforcement mechanism. PMID- 3092071 TI - Turning behavior induced by phencyclidine: relationship to antagonism of N-methyl D-aspartate in the rat striatum. PMID- 3092072 TI - The reinforcing and rate effects of intracranial dopamine administration. PMID- 3092073 TI - How effective is LAAM treatment? Clinical comparison with methadone. PMID- 3092074 TI - Major patterns of polydrug abuse among heroin addicts. PMID- 3092075 TI - Metabolic mapping of the cerebral effects of abused drugs. PMID- 3092076 TI - Treatment of cocaine abuse. PMID- 3092077 TI - Cocaine treatment outcome: cocaine use following inpatient, outpatient, and no treatment. AB - Based upon a sample of 83 cocaine users self-selected into one of 3 programs, several conclusions seem possible. There seems to be little difference in Ss populations who choose hospital, outpatient or self-help/no treatment. Current hospital aftercare programs may not be appropriately oriented for cocaine users. It appears the hospital program in this study retained fewer than 30% of the Ss in aftercare. Outpatient treatment for cocaine dependency is a viable form of treatment which Ss will participate in for up to 6 months on a fee for service basis. Only about 20% of the Ss who were referred to self-help groups attended more than one meeting. Preliminary outcome data suggest that outpatient treatment may result in a lower relapse rate to cocaine than hospital or no treatment. However, this conclusion is extremely guarded due to a large number of methodological issues and the short follow-up period. Relapse to cocaine use is higher among Ss who returned to alcohol or marijuana. PMID- 3092078 TI - Abuse of cocaine with opioids: psychological aspects of treatment. PMID- 3092079 TI - Descriptive epidemiology of adult cocaine use in four U.S. communities. PMID- 3092080 TI - Psychological issues in the treatment of cocaine abuse. PMID- 3092081 TI - Use of nonnarcotic drugs by narcotic addicts. PMID- 3092082 TI - Drug dependence in pregnancy: intrapartum course and management. PMID- 3092083 TI - Long-term followup studies of the medical status of adolescent former heroin addicts in chronic methadone maintenance treatment: liver disease and immune status. PMID- 3092084 TI - Double-blind comparison of desipramine and placebo for treatment of phencyclidine or amphetamine dependence. AB - Open clinical trials have suggested that desipramine may be an effective agent for treatment of phencyclidine (PCP) or amphetamine dependence. Four pairs (eight subjects) with PCP and two pairs (four subjects) with amphetamine dependence were studied. One subject in each pair was given desipramine or placebo under double blind conditions. Although desipramine clearly was no more effective than placebo in treatment of PCP dependence, subjects with amphetamine dependence who received desipramine remained in treatment longer and submitted more urine samples absent of amphetamine than did subjects who received placebo. PMID- 3092085 TI - Antibody to LAV, the putative agent of AIDS, in parenteral drug abusers and methadone-maintained patients: therapeutic, historical, and ethical aspects. PMID- 3092086 TI - The effects of cannabis use on the clinical condition of schizophrenics. PMID- 3092088 TI - Disparity in hemispheric and thalamic growth in infants undergoing abstinence. PMID- 3092087 TI - Effects of cocaine on pregnancy outcome. PMID- 3092089 TI - Naloxone-precipitated withdrawal in humans after acute morphine administration. PMID- 3092090 TI - Behavioral pharmacology of licit drugs in experimental animals. PMID- 3092091 TI - Chronic naltrexone effect on cortisol. PMID- 3092092 TI - Nature and incidence of conditioned responses in a methadone population: a comparison of laboratory, clinic, and naturalistic settings. PMID- 3092094 TI - Treatment outcome in cocaine abusers. PMID- 3092093 TI - CSF endorphins in chronic opioid-dependent humans. PMID- 3092095 TI - Biological evaluation of compounds for their physical dependence potential and abuse liability. IX. Drug Testing Program of the Committee on Problems of Drug Dependence, Inc. (1985). PMID- 3092096 TI - Dependence studies of new compounds in the rhesus monkey, rat, and mouse (1985). PMID- 3092097 TI - Nathan B. Eddy Memorial Award lecture. PMID- 3092099 TI - Naltrexone hydrochloride (Trexan): a review of serum transaminase elevations at high dosage. AB - In summary, evidence is presented associating typically asymptomatic and reversible elevations of serum transaminase values with high daily dosages of naltrexone. Statistical significance was found only between placebo and the 300 mg dosage. Subjects aged 40 years and over were significantly more likely to develop this finding than younger subjects. All subjects with significant elevations of transaminase values in these studies took daily naltrexone dosages higher than recommended for opioid addiction. The daily dosage of naltrexone recommended for opioid addiction did not cause abnormalities of serum transaminase values in these studies. PMID- 3092098 TI - Human studies of the behavioral pharmacological determinants of nicotine dependence. PMID- 3092100 TI - Naltrexone (Trexan): a review of hepatotoxicity issues. PMID- 3092101 TI - Progress report from the Medical College of Virginia: abused solvents. PMID- 3092102 TI - Progress report from the Division of Behavioral Biology, the Johns Hopkins University School of Medicine. PMID- 3092103 TI - Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma. AB - The application of recombinant DNA techniques has identified two fundamental mechanisms of tumorigenesis in man. The first involves a qualitative or quantitative change in an oncogene (see ref. 1 for review). In the second, discovered in embryonal tumours, a primary mutation occurs which is recessive at the cellular level to the normal allele. The growth of a tumour ensues only after a secondary change, such as chromosome loss or mitotic recombination, eliminates the normal allele, thereby unmasking the altered allele. Because its effect is recessive, the primary mutation may also occur and be transmitted in the germ line, resulting in a familial pattern for the disease. In familial cases, independent bilateral tumours are common, since the tumours result from a single event--loss of the normal genes--which can occur in any cell. This contrasts with non-familial (sporadic) cases where solitary tumours result from the infrequent occurrence of two rare events within the same cell. By a molecular genetic approach we have now shown that acoustic neuroma, one of the most common tumours of the human nervous system, is specifically associated with loss of genes on human chromosome 22 and may result from the mechanism of tumorigenesis discovered in embryonal tumours. This finding might provide a clue to the chromosomal location of the defective gene in bilateral acoustic neurofibromatosis, an autosomal dominant disorder with the hallmark of bilateral acoustic neuromas. In view of the frequent occurrence of meningiomas in patients with bilateral acoustic neurofibromatosis and the association of meningioma with loss of chromosome 22 previously reported in cytogenetic studies, we suggest that a common event underlies tumorigenesis in acoustic neuroma and meningioma. PMID- 3092104 TI - Antibody diversity. New mechanism revealed. PMID- 3092105 TI - A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production. AB - During B-cell development, the VH genes of immunoglobulin heavy (H) chains are assembled from three different germline components: the variable (VH) segment, the diversity (D) segment and the joining (JH) segment. The joining between two segments involves the recognition of conserved nonamer-heptamer sequences bordering each segment, double-stranded cuts at the heptamer-segment border, and the re-ligation of the two segment ends which have frequently been modified by the deletion and addition of nucleotides. The flexibility of the joint increases VHDJH variability. However, it also results in many pre-B cells which do not produce immunoglobulin H chains and have non-functional VHDJH complexes carrying the VH and JH coding sequences in different reading frames. We show here that such 'null cells' are not dead-end products of the B-cell developmental pathway but can perform a novel VH to VHDJH joining using a 5' VH segment to replace the VH sequence of the VHDJ-H complex. This process can result in the generation of a VHDJ+H complex and the subsequent expression of an immunoglobulin heavy chain. PMID- 3092106 TI - Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma. AB - The early stages of murine B-cell differentiation are characterized by a series of immunoglobulin gene rearrangements which are required for the assembly of heavy(H) and light(L)-chain variable regions from germline gene segments. Rearrangement at the heavy-chain locus is initiated first and consists of the joining of a diversity (DH) gene segment to a joining (JH) gene segment. This forms a DJH intermediate to which a variable (VH) gene segment is subsequently added. Light-chain gene rearrangement follows and consists of the joining of a VL gene segment to a JL gene segment: once a productive light-chain gene has been formed the cell initiates synthesis of surface immunoglobulin M (sIgM) receptors (reviewed in ref. 1). These receptors are clonally distributed and may undergo further diversification either by somatic mutation or possibly by continued recombinational events. Such recombinational events have been detected in the Ly 1+ B-cell lymphoma NFS-5, which has been shown to rearrange both lambda and H chain genes subsequent to the formation of sIgM (mu kappa) molecules. Here we have analysed a rearrangement of the productive allele of NFS-5 and found that it is due to a novel recombination event between VH genes which results in the replacement of most or all of the coding sequence of the initial VHQ52 rearrangement by a germline VH7183 gene. Embedded in the VH coding sequence close to the site of the cross-over is the sequence 5' TACTGTG 3', which is identical to the signal heptamer found 5' of many DH gene segments. This embedded heptamer is conserved in over 70% of known VH genes. We suggest that this heptamer mediates VH gene replacement and may play an important part in the development of the antibody repertoire. PMID- 3092107 TI - Distinct factors bind to apparently homologous sequences in the immunoglobulin heavy-chain enhancer. AB - The intron separating the variable- and constant-region exons of the rearranged immunoglobulin heavy-chain locus contains a lymphocyte-specific transcriptional enhancer. The enhancer is a member of a class of cis-acting, tissue-specific, transcriptional control elements which are characterized by orientation independent and relatively position-independent function. In vivo analysis of the position of DNA-binding factors, by assessing the availability of specific bases to chemical modification, has identified four sequence clusters within the heavy chain enhancer, denoted E1 to E4 (refs 3, 4). These sites are protected (that is, occupied) only in B lymphocytes. A consensus sequence relationship (consensus CAGGTGGC) between these four sites was suggested where three of the sites conformed to the consensus in seven of eight positions while the other was homologus in six of eight positions. We proposed that a single trans-acting factor might recognize all four sites. Using an assay involving gel electrophoresis of DNA-protein complexes to detect sequence-specific DNA binding factors that recognize these related motifs, we have now identified a mouse B cell nuclear factor (NF-muE1) which binds specifically to one such motif within the mouse heavy-chain gene enhancer. This factor binds poorly, if at all, to the other related motifs, and other factors have been identified which interact preferentially with some of these latter motifs. Dimethyl sulphate interference experiments suggest that the NF-muE1 factor is in contact with at least the guanine residues in the sequence GATGGCCGATC. This factor seems to be present in both lymphoid and non-lymphoid cell lines. PMID- 3092109 TI - Blood products: hepatitis screening extended. PMID- 3092108 TI - A molecular link between the bats of New Zealand and South America. AB - Along with the kiwis (Apteryx), tuatara (Sphenodon) and leiopelmatid frogs, the now rare lesser short-tailed bat (Mystacina tuberculata), one of only two species in the endemic family Mystacinidae, has long been viewed as one of New Zealand's archaic, mystery vertebrates, and has presented taxonomists with a major puzzle since its first description in 1843 (ref. 3). We report here the results of immunological comparisons involving the albumin and transferrin of Mystacina which indicate that its closest phylogenetic affinities are with the New World phyllostomoids--noctilionids, mormoopids and phyllostomoids. We estimate the separation between the Noctilio and Mystacina lineages to have occurred about 35 Myr ago. PMID- 3092110 TI - Good prospects for lion tamarins. PMID- 3092111 TI - Striking similarities between antigen receptor J pieces and sequence in the second chain of the murine CD8 antigen. AB - The CD8 antigen is a marker for T-lymphocyte subsets that is absent from helper T cells but expressed on cytotoxic T cells which recognize foreign determinants in association with class I major histocompatibility complex (MHC) antigens. It has been suggested that CD8 plays some part in recognition by CD8+ cytotoxic T cells since anti-CD8 antibodies can block their functions and the human CD8 antigen contains a domain with clear similarities to immunoglobulin and T-cell receptor (TCR) variable-region (V) domains. Human CD8 antigen is thought to be a homodimer but in the mouse and rat the equivalent antigens (alternatively called Lyt2,3 and OX8) are heterodimeric. Rat CD8 contains two chains of relative molecular mass 32,000 (32K) and 37K: the 32K chain is the rat homologue of human CD8 and mouse Lyt2. We describe here the molecular cloning of the rat 37K chain using an oligonucleotide probe predicted from peptide sequence. The full protein sequence is derived from the complementary DNA and matches limited peptide sequence for mouse Lyt3. The new sequence is more like immunoglobulin and T-cell receptor V domains than other T-cell antigens and includes a patch that is almost identical to some joining (J) piece sequences. This suggests that the CD8 and receptor heterodimers may have evolved directly from a common ancestor. PMID- 3092112 TI - Cameroon disaster: carbon dioxide blamed. PMID- 3092113 TI - Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1. AB - Activated monocytes or macrophages can release soluble cytotoxic molecules capable of lysing tumour cells in vitro and thus represent an important component of the host defence mechanisms against malignancy. The recent availability of pure recombinant or natural human lymphokines and monokines and their respective polyclonal or monoclonal antibodies now makes it possible to dissect the interactions of these factors in the induction and performance of the cytotoxic event by the monocytes. Our studies indicate that pretreatment of monocytes with alpha-IFN or gamma-IFN, and also interleukin (IL)-1 or tumour necrosis factor (TNF) results in enhanced monocyte cytotoxicity. Although all these substances induce the production of IL-1 by monocytes, TNF mediates the enhanced cytotoxicity induced in monocytes by gamma-IFN, IL-1 and, in an autocrine manner, by TNF itself. Neither TNF, IL-1, gamma-IFN nor alpha-IFN mediate spontaneous monocyte cytotoxicity or that induced by alpha-IFN. Our studies thus reveal new interactions between the two monokines IL-1 and TNF and provide a dual role for TNF, as immunomodulator and mediator of monocyte cytotoxicity induced by certain specific lymphokine and monokine molecules. PMID- 3092114 TI - G-protein control of inositol phosphate hydrolysis. PMID- 3092115 TI - [Sexually transmissible diseases and infertility]. PMID- 3092117 TI - The effects of prospective payment (DRGs) on nursing: conjecture or reality? PMID- 3092116 TI - Management moves. PMID- 3092118 TI - [Value of the video simultaneous double image technic in epilepsy diagnosis]. PMID- 3092119 TI - [Single evening administration of slow release carbamazepine]. PMID- 3092120 TI - [Dialysis encephalopathy and aluminum poisoning? Correlated clinical, pathologic anatomic and spectrometric findings]. AB - A case of severe dialysis encephalopathy is reported, in which the autopsy finding of an extensive spongiform change in areas of the cortex directly corresponded to high aluminium-concentration in these areas, supporting the theory of an aetiological role for aluminium. A therapeutic approach combining low aluminium intake and removal of aluminium by a chelating agent (desferrioxamine) is promising, but more precise guidelines are needed. PMID- 3092121 TI - Chronic lead accumulation as a possible cause of renal failure in gouty patients. AB - Gout rarely develops in nephropathy with advanced renal failure unless other risk factors are present. It has recently been demonstrated that gouty patients with renal failure have greater amounts of mobilizable lead. We have used the EDTA lead mobilization test for 12 gouty patients with renal impairment. Only 7 of these had experienced occupational exposure to lead. 12 patients with nephropathy caused by chronic glomerulonephritis, without a history of gout or lead exposure, were selected as controls. The urinary excretion of lead after the mobilization test was significantly higher in gouty patients. Only in gouty patients was lead excretion directly correlated with the serum creatinine level. Thus, renal failure did not induce any increase in mobilizable lead. Since it is not infrequent in Italy to observe patients with a progressively declining renal function due to chronic interstitial nephritis and with a previous history of gout, we think the EDTA test will be useful to look for lead storage in these patients. PMID- 3092122 TI - Dynamics of thyrotropin-releasing hormone-induced thyrotropin and prolactin secretion by acutely dispersed rat adenohypophyseal cells. Evidence for 'all-or none' secretion by heterogeneous secretory units, each with a specific response threshold. AB - We have examined the dynamics of thyrotropin-releasing hormone (TRH)-stimulated secretion of prolactin (PRL) and thyrotropin-stimulating hormone (TSH) using enzymatically dispersed rat adenohypophyseal cells suspended in a perfusion chamber with a volume of 0.2 ml to minimize mixing and dilution. One-min exposure to 3-300 nM TRH, the effective dose range, elicited immediate pulses of PRL and TSH secretion with dose-dependent amplitudes. At all TRH concentrations, following a brief burst of secretion lasting less than 1 min, release of both hormones declined precipitously. Increasing the duration of stimulation up to 30 min with half-maximal TRH concentrations did not alter the dynamics of the initial response and was ineffective in maintaining the initial amplitude of secretion. This phenomenon could not be attributed to exhaustion of readily releasable intracellular PRL and TSH, since an increment in TRH concentration elicited a second pulse of hormone secretion with temporal response characteristics identical to the first. The amplitude of the second pulse was dependent on both the initial concentration of TRH and the magnitude of the increment in TRH concentration. With a stepwise increase in TRH concentration during continuous perfusion, the sum of PRL or TSH secreted from all bursts of secretory activity approximated that achieved with a single exposure to the highest concentration of TRH employed. The high-amplitude secretory response to a given concentration of TRH was restored after an 8-min perfusion with medium alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092123 TI - Different neuroendocrine mechanisms regulate the acute pituitary follicle stimulating hormone response to orchidectomy and ovariectomy. AB - The following experiments were conducted to determine whether a sex difference exists in neuroendocrine mechanisms controlling acute pituitary follicle stimulating hormone (FSH) responses to castration. Adult male rats and 4-day cycling female rats on diestrus 1 were injected intraperitoneally with either phenobarbital sodium (PhB, 80 mg/kg b.w.) or vehicle at 08:00 h. Following a blood collection at 10:00 h, rats given PhB or vehicle were either sham castrated or castrated under ether. Additional blood samples were obtained, and supplemental PhB or vehicle injections were given at 3, 8, 13, 18, and 24 h after castration. Administration of PhB to male rats completely prevented acute increases in plasma luteinizing hormone (LH) and FSH levels after orchidectomy (ORDX). In contrast, PhB treatment did not prevent initial rises in plasma FSH levels at 8 h after ovariectomy (OVX) and only partially suppressed OVX-induced increases in plasma FSH levels between 13 and 24 h. Plasma LH levels were not elevated by 24 h after OVX. In order to specifically evaluate the role of LH releasing hormone (LHRH) in mediating the PhB-sensitive rises in gonadotropins after castration, groups of male rats and female rats on estrus were injected subcutaneously with 400 micrograms of a potent LH-RH antagonist (ALHRH) or oil at 12:00 h. At 10:00 h on the next morning, an initial blood sample was taken, and all rats were castrated under ether. Additional blood samples were taken at times indicated in the previous experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092124 TI - Increased sensitivity of adenylate cyclase activity in the striatum of the rat to calmodulin and GppNHp after chronic treatment with haloperidol. AB - Chronic treatment of rats with haloperidol causes behavioral supersensitivity to dopaminergic agonists and an increase in the sensitivity of adenylate cyclase activity in the striatum to stimulation by dopamine. In this study the authors examined whether chronic treatment with haloperidol could elicit a change in sensitivity of adenylate cyclase in the striatum of the rat for guanyl nucleotides and the endogenous Ca2+-binding protein, calmodulin. These agents increase the activation of adenylate cyclase activity by dopamine but act beyond the level of the dopamine receptor. Male, Sprague-Dawley rats were injected subcutaneously with either 0.6 mg/kg haloperidol or vehicle for 14 days. Four days after the last injection, the animals were sacrificed and the activity of adenylate cyclase was measured in a EGTA-washed particulate preparation of the striatum. There was an increase in the activation of adenylate cyclase activity by calmodulin and GppNHp but not by guanosine triphosphate (GTP) in particulate fractions of the striatum from rats treated with haloperidol as compared to controls. The sensitivity of adenylate cyclase to calmodulin was increased 5-fold in particulate fractions from rats treated with haloperidol as opposed to vehicle treated rats. The lack of change in activation by GTP was not due to an altered activity of GTPase in rats treated with haloperidol. In animals treated for 14 days but not withdrawn from haloperidol there was no statistically significant increase in the sensitivity of adenylate cyclase to calmodulin. There was no change in activation of the enzyme by GppNHp or GTP as compared to control. The activation of adenylate cyclase by calmodulin was not affected when haloperidol was added in vitro to the assay or after the acute injection of rats with haloperidol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092126 TI - Anticonvulsant properties of flunarizine on reflex and generalized models of epilepsy. AB - The anticonvulsant activity of 1-bis(4-fluorophenyl)methyl-4-(3-phenyl-2 propenyl)-piperazine, flunarizine, was studied after intraperitoneal administration in DBA/2 mice (seizures induced by sound), intravenous administration in Papio papio (myoclonus induced by photic stimulation) and oral administration in Wistar rats (seizures induced by cefazolin). Protection against sound-induced seizures was observed after intraperitoneal administration of flunarizine (5-40 mg/kg). The ED50 for suppression of tonic, clonic and wild running phases of sound-induced seizures was 3.3, 9.8 and 17.5 mg/kg, respectively. This protective action was significantly reduced by pretreatment with aminophylline (50 mg/kg, i.p.). In photosensitive baboons flunarizine (0.5 1.0 mg/kg, i.v.) provided partial protection against myoclonic responses to stroboscopic stimulation. After flunarizine (2 mg/kg, i.v.) this protection lasted for more than 5 hr (and was complete at 2-3 hr). Cefazolin-induced seizures in rats were prevented by administration of flunarizine (20-40 mg/kg, orally). The ED50 for the suppression of tonic and clonic seizures evoked by subsequent intravenous administration of cefazolin was 25 mg/kg. The protective effects of flunarizine (40 mg/kg, orally) were maximal after 3-6 hr and were maintained for 16-24 hr. Behavioural effects of flunarizine included signs of sedation in both mice and rats. Tolerance to the antiepileptic effects of flunarizine was not seen after chronic treatment in rats. The role of purinergic receptors and of calcium entry blockade in the anticonvulsant action of flunarizine requires further study. PMID- 3092125 TI - Differential effect of gamma-vinyl GABA and valproate on GABA-transaminase from cultured neurones and astrocytes. AB - A preferential effect of valproate on gamma-aminobutyric acid (GABA) in the nerve terminal compartment has been proposed. Gamma-vinyl GABA, an irreversible inhibitor of GABA-transaminase (GABA-T) causes a preferential increase in the GABA compartment of the non-nerve terminal. The aim of the present study was to investigate further this apparent differential effect on GABA-T of these compounds in neurones and glia. The investigations were undertaken in neurones and astrocytes, cultured separately. After incubation with valproate, the IC50 value for astrocytes was found to be 1202 microM of valproate and for neurones 634 microM. Assuming regional differences of concentrations of valproate in the brain, the observed IC50 values might be clinically relevant. Culturing the cells in the presence of gamma-vinyl GABA demonstrated IC50 values for astrocytes and neurones of 89 and 24 microM, respectively. The (S)isomer of gamma-vinyl GABA was the most active inhibitor of GABA-T in both glia and neurones. After withdrawal of gamma-vinyl GABA from the culture media of the cells, in neurones 50% of the activity of GABA-T was regained within 2-4 days. In astrocytes a similar time course was observed. These findings are in agreement with clinical data: the IC50 values correspond to clinically-relevant serum levels of gamma-vinyl GABA in humans only the (S)isomer showed an antiepileptic effect in animal models of epilepsy a delayed antiepileptic effect, after withdrawal of gamma-vinyl GABA, has been established in clinical studies. PMID- 3092127 TI - Concentrations of GABA and glycine in discrete brain nuclei. Stress-induced changes in the levels of inhibitory amino acids. AB - Concentrations of gamma-aminobutyric acid (GABA), glycine and serine have been measured in 44 microdissected areas of the brain of the rat. All three amino acids were ubiquitously present and distributed unevenly in the brain. Very high levels of GABA were found in the anterior hypothalamic and medial preoptic nuclei and the substantia nigra; high levels were found in the interpeduncular and red nuclei in the mesencephalon and in several hypothalamic nuclei. Glycine was distributed fairly uniformly with large concentrations in certain lower brainstem nuclei. In these areas, the concentrations of glycine exceeded those of serine, while the serine-glycine ratio was 4.5:1 in the caudate nucleus, 4:1 in the cerebellum and 2.5:1 in the cerebral cortical areas. Acute stress induced with formalin (pain) resulted in a significant depletion of levels of GABA in the hypothalamus and the lower brainstem but not in the cortical areas. In the same animals, concentrations of glycine doubled in the cerebral cortex and remained unchanged elsewhere in the brain. Increased motor and behavioral activity after the acute administration of a large dose of amphetamine were associated with a 2 5-fold increase in the levels of glycine in brain, and markedly elevated the concentrations of GABA in the major biogenic amine-containing cell groups only (substantia nigra, locus coeruleus and dorsal raphe). PMID- 3092128 TI - Ossification of the posterior longitudinal ligament in Caucasians: diagnosis and surgical intervention. AB - Six cases of ossification of the posterior longitudinal ligament (OPLL) in Caucasians have been diagnosed during a 2-year period at Walter Reed Army Medical Center. Five cases were in men and one was in a woman. Three cases presented as myelopathy and three as radiculopathy. Diagnosis was best confirmed with computer assisted tomography. All six cases were treated surgically via an anterior approach, microsurgical resection of the OPLL, and autograft fusion. Patients with radiculopathy had immediate pain relief after operation. Those with myelopathy required vertebrectomy and regained strength after operation. All patients improved with operation. OPLL is not a rare condition in Caucasians. With diagnosis and proper surgical intervention, prognosis for improvement is good. PMID- 3092129 TI - State of the effect of long-term administration of thyrotrophin releasing hormone to rats on the posterior lobe of the pituitary. PMID- 3092130 TI - Amyotrophic lateral sclerosis: thyrotropin-releasing hormone and histidyl proline diketopiperazine in the spinal cord and cerebrospinal fluid. AB - In spinal cords from seven amyotrophic lateral sclerosis (ALS) patients and four controls, we found no difference in thyrotropin-releasing hormone (TRH) concentration relative to protein content, but there was a reduction per tissue wet weight in ALS. Immunohistochemical localization of TRH in ALS cord was unaltered. Histidyl proline diketopiperazine (HisPro-DKP), a possible metabolite of TRH, was significantly elevated per protein content in ALS. CSF levels of TRH and HisPro-DKP were unchanged. These findings suggest that TRH neurons are not primarily affected in ALS, but TRH and tissue protein are lost together as the disease progresses. PMID- 3092131 TI - Seizures and myoclonus in patients with Alzheimer's disease. AB - We reviewed 81 patients with dementia and autopsy findings of Alzheimer's disease (AD) to identify patients with seizures or myoclonus after onset of dementia. Eight (10%) had seizures, and eight others (10%) had myoclonus. The incidence of seizures was 10 times more than expected in a reference population. Seizures occurred in any stage of AD, but myoclonus was often a late manifestation. Both seizures and myoclonus, individually or together, are manifestations of AD and may be seen at any time in the course of the illness. PMID- 3092132 TI - Cerebral infarct, TIA, and lupus inhibitor. AB - A lupus inhibitor paradoxically prolongs phospholipid-dependent coagulation assays, but may increase risk of thromboembolism. We studied seven patients with cerebral infarcts and one with TIA who had lupus inhibitor. The average age at onset of cerebral ischemia was 41 years. Three patients had multiple cerebral ischemic events. The activated partial thromboplastin time was longer than that of controls, but usually within normal limits. Other abnormalities included biologic false-positive VDRL, antinuclear antibodies, thrombocytopenia (three patients each), and deep vein thrombosis (two patients). PMID- 3092133 TI - Atypical adult GM1 gangliosidosis: biochemical comparison with other forms of primary beta-galactosidase deficiency. AB - We studied beta-galactosidase in skin fibroblasts from patients with different forms of beta-galactosidase deficiency: adult GM1 gangliosidosis, type 1 GM1 gangliosidosis, and Morquio B syndrome. Enzyme properties in the adult cases differed from the other disorders and also from normal controls. Genetic hybridization studies indicated that all three forms belong to the same complementation group. Therefore, the adult disorder must be due to a mutation of the structural gene for beta-galactosidase, which is allelic to the mutations in type 1 GM1 gangliosidosis and Morquio B syndrome. PMID- 3092134 TI - Atypical inclusion body progressive myoclonus epilepsy: a fifth case? PMID- 3092135 TI - Biological terrorism: a direct threat to our livestock industry. PMID- 3092136 TI - An analysis of dental emergencies during combat and peacetime exercises. PMID- 3092137 TI - The effect of anesthetic, sedative or narcotic drugs on intrahepatic and extrahepatic biliary kinetics. PMID- 3092138 TI - Health fraud: a growing problem. PMID- 3092139 TI - Diagnostic related group (DRG's) and military health facilities: competition or coordination? PMID- 3092140 TI - A new approach to Army Reserve medical officer recruitment. PMID- 3092141 TI - Phenylpropanolamine anorexiants and affective disorders. PMID- 3092142 TI - The epidemiology of acute pharyngitis among soldiers at Fort Lewis, Washington. PMID- 3092143 TI - Immediate hypersensitivity skin testing for penicillin allergy. PMID- 3092144 TI - Intraoperative endoscopy as a diagnostic tool. PMID- 3092145 TI - Polypectomy consent. PMID- 3092146 TI - Educational preparation of the military dental officer for contingency. PMID- 3092147 TI - Hearing conservation in U.S. Naval Submarine Force. PMID- 3092148 TI - [Polycystic ovaries and infertility. Incidence, characteristics, therapy and prognosis]. PMID- 3092149 TI - Serum C-reactive protein in systemic infections due to Neisseria meningitidis. AB - The results of C-reactive protein (CRP) measurements in 176 patients hospitalized with suspected systemic meningococcal disease (MCd) are presented. 115 patients had meningococcal disease and 61 patients had other diseases and served as control patients. On admission to hospital high CRP levels were found in patients with meningococcal disease, markedly above the levels found in patients with viral infections. The CRP level fell to nearly normal level during the first week of treatment. CRP on admission to hospital had no prognostic value. Pretreatment CRP level can be valuable in the differential diagnosis between meningococcal disease and other diseases. PMID- 3092151 TI - Peripheral and central nutritional support. PMID- 3092150 TI - Spartanburg General Hospital policy book on i.v. therapy administration--Part II. PMID- 3092152 TI - Hypophysectomy does not alter the increase in striatal dopamine receptor density produced by 6-hydroxydopamine lesions in male rats. AB - While hypophysectomy can alter the increase in striatal dopamine (DA) receptor density observed after estrogen, haloperidol or prolactin treatments, it does not alter the increase in density found after 6-hydroxydopamine lesions of the DA neurons in male rats. This observation suggests that striatal DA receptors can be regulated by at least two distinct mechanisms, only one of which requires the availability of pituitary hormones. PMID- 3092153 TI - Thyroid dysfunction in protein-calorie malnutrition. PMID- 3092154 TI - Alterations in thyroid function in protein-calorie malnutrition. PMID- 3092155 TI - The preparation and in vivo behaviour of 111In-oxine labelled neutrophils separated from whole blood using mono-poly resolving medium. AB - using a single step separation procedure, we have developed a method for labelling human neutrophils with 111In-oxine. This method allows a rapid separation of neutrophils from whole blood, with negligible mononuclear or red cell contamination. Preliminary studies using 111In-labelled neutrophils show minimal lung retention and early accumulation in the spleen consistent with viable cells. In addition, focal accumulation of 111In has been imaged in patients with localized inflammation or sepsis. PMID- 3092157 TI - Health promotion pays: 3-to-1 return seen in stress management programs. PMID- 3092156 TI - Total parenteral nutrition during pregnancy. AB - Parenteral hyperalimentation or total parenteral nutrition has become an established therapy for patients with a wide variety of conditions that preclude oral feeding. Because pregnancy is an infrequent event in poorly nourished women with acute or chronic illness, total parenteral nutrition has not been widely used for pregnant patients. Some obstetricians believe that total parenteral nutrition entails risks in excess of its potential benefit to pregnancy and demands skills and knowledge that are either not available or are in limited supply. Sufficient favorable clinical experience has accumulated over the past 15 years so that total parenteral nutrition can be recommended in the management of malnutrition during pregnancy. The purpose of this report is to review the authors' experience and the literature about total parenteral nutrition during pregnancy. PMID- 3092159 TI - An evaluation of the efficacy and irritability of Sporicidin as a hand dip. AB - Sporicidin, diluted 1:16, used as a disinfectant hand dip, was found to produce substantial percent reductions in the mean number of colony-forming units in comparisons between microbial recoveries of the control and Sporicidin-dipped hands. Sporicidin at this concentration appears to demonstrate efficacy as an antimicrobial agent, but dermal irritation, sensitivity and yellowing of the skin, and its objectionable odor may preclude its routine clinical use. PMID- 3092158 TI - [Mutant gene expression in mouse aggregation chimeras. 6. An analysis of the effects of the white gene using a histochemical marker]. AB - The Miwh expression was studied using a genetical marker, acid beta galactosidase, in 20 day old chimeric mice Miwh/Miwh Bglb/Bglb C/C in equilibrium +/+ Bgld/Bgld C/Ca and Miwh/Miwh Bglb/Bglb C/C in equilibrium +/+ Bgld/Bgld c/c. Three phenotypically new types of the retinal pigment epithelium (RPE) regions were found in the chimeras, which were absent in the RPE of the parental strains. The presence in the chimeras of the RPE regions consisting of pigmented and normally differentiated cells with a high activity of the enzyme suggests the normalization of differentiation of the Miwh/Miwh RPE cells, due, apparently, to the inducing influence of the normal (+/+ C/C) mesenchyme cells. In addition, the presence of nonpigmented, both hyperplasied and nonhyperplasied, RPE regions (+/+ C/C) suggests an insufficient growth-inhibiting influence and the absence of melanogenesis-stimulating activity of defective Miwh/Miwh ectomesenchyme. The histochemical and cytological analysis of the RPE in the obtained chimeras has, thus, shown that the Miwh gene primarily affects ectomesenchyme, which does not exert melanogenesis-stimulating and growth-inhibiting influence on the RPE ensuring its hyperplasia and the absence of pigmentation. PMID- 3092161 TI - RUGs II: implications for management and quality in long term care. AB - Case-mix-based reimbursement could provide long term care facilities with a financial incentive to accept the more acutely ill patients who are being discharged from hospitals under Medicare's prospective payment system. But a financial incentive to maintain a complex case mix could also encourse nursing homes to provide substandard care. New York's Medicaid program has coupled a reimbursement method based on Resourse Utilizationm Groups (RUGs II) with regulatory efforts to ensure quality in a model that may be be adopted by Medicare and by Medicaid programs in other states. This article describes New York's system and discusses a number of management and quality assurance strategies that may be useful to nursing homes under RUGs II. PMID- 3092160 TI - Responsibilities for quality assurance in prehospital care. PMID- 3092162 TI - Follow-up of nosocomial infections on nursing units: an approach to infection control. AB - The infection control department at Niagara Falls Memorial Medical Center in Niagara Falls, New York, has developed an innovative approach to decreasing nosocomial infections. By following up on the infections that occur on nursing units, nurses actively work to prevent their occurrence. The approach utilizes nursing accountability, continuing staff education, and documentation, with positive results. PMID- 3092164 TI - Swing beds for small or rural hospitals. AB - One hundred percent PRO review is only one of many issues small or rural hospitals must consider when contemplating the use of swing beds. Other areas of consideration, according to Mr Losoff, include: local nursing homes that perceive competition; low utilization rates that may result in little additional income; the need to monitor resources that are allocated to swing-bed patients; more acutely ill patients who demand more intense services; and the lack of experience with swing beds by state officials and fiscal intermediaries. Despite these potential drawbacks, quality-of-care concerns and cost-containment efforts inherent in the successful use of the swing-bed concept can work to the hospitals' benefit. They can use staff more efficiently; increase patient access to physicians; increase income slightly; and provide diversification opportunities. The patients also benefit from these advantages as well as from those previously mentioned. However, the complexities of the swing-bed concept necessitate that hospitals carefully consider and completely understand the advantages and disadvantages as they relate to each individual situation before considering this an option, much less the aforementioned panacea. Or, as Mr Losoff advised, "Do a lot of planning. And when you're ready to do it keep your fingers crossed, take a deep breath, and go forward". PMID- 3092163 TI - Planning for quality in the home care system. AB - The cycle of quality planning includes five steps needed to establish a home care quality program. These include commitment, development, communication, implementation, and evaluation of a workable quality of care strategy. Tools available as control mechanisms when implementing the system are patient rights, home evaluation, documentation of care, and performance evaluation. Upon patient discharge, an entire case is reviewed and summarized for future reference and audit. In approaching the challenge of quality care, home care management must be aware that quality permeates every aspect of operations and is not confined to the functional domain of a committee or to the administrative bounds of a specific program. Quality is an overall measure of performance and should be respected as such at all levels of the organization. A summary list of guidelines for enforcing quality in home health care operations is presented in Figure 3, page 251. This figure, as with other suggestions presented in this article, reinforces the same general message: articulate, communicate, and evaluate. Cost effective, high-quality home health care is becoming significantly more desirable as the number of home health agencies rises and the potential for prospective payment by the federal and state programs and the health maintenance organization concept expand. In addition, the prospect of the Joint Commission on Accreditation of Hospitals' developing an accreditation program for all home health care agencies offers the opportunity to have baseline data for building and measuring QA. PMID- 3092165 TI - Trends in quality assurance activities in France. PMID- 3092166 TI - Schistosoma mansoni: liver phase challenge attrition is a stage-dependent phenomenon in guinea-pigs vaccinated with highly irradiated cercariae. AB - Guinea-pigs vaccinated with highly irradiated cercariae of Schistosoma mansoni have been examined for their ability to kill challenge parasites at the level of the liver. Skin and lung phase attrition were eliminated by surgical introduction of 4/5 day old schistosomula, or 2, 3 or 6 week schistosomes into the mesenteric vasculature of vaccinated and naive animals. These experiments showed consistently that lung schistosomula and 2 week old parasites were killed preferentially by sensitized animals, but that older worms were refractory. Liver phase immune elimination would therefore seem to be a stage-dependent phenomenon in the vaccinated guinea pig model of schistosomiasis. PMID- 3092167 TI - Inhibition of human peripheral blood mononuclear cell proliferative responses by released materials from Schistosoma mansoni cercariae. AB - During in vitro transformation of Schistosoma mansoni cercariae into schistosomula, surface and glandular materials are released into the culture medium. Extracts of these materials, termed cercarial released extracts 1 and 2 (CRE-1 and CRE-2), were analysed and found to consist primarily of protein and carbohydrate at ratios of 5:1 (CRE-1) and 7:1 (CRE-2). It was observed that inclusion of either CRE-1 or CRE-2 in cultures of human peripheral blood mononuclear cells (PBMN) led to decreased cell proliferation. This was true whether the cells were resting, control cultures or were stimulated with either phytohaemagglutinin or an antigenic preparation from adult S. mansoni worms. The inhibition was equally effective with PBMN of patients with active schistosomal infection or PBMN from uninfected individuals. Since these materials are released spontaneously during cercarial-to-schistosomular transformation they may have a putative immunosuppressive effect in decreasing antischistosomular activities early after cercarial penetration. PMID- 3092168 TI - Specific lysis of Theileria annulata-infected lymphoblastoid cells by a monoclonal antibody recognizing an infection-associated antigen. AB - A monoclonal antibody (4H5) recognizing a Theileria annulata infection-associated antigen was assayed to see if it could either suppress the proliferation of T. annulata-infected lymphoblastoid cells, as monitored by the incorporation of tritiated thymidine by proliferating host cells, or lyse T. annulata-infected lymphoblastoid cells, as assessed by counts of target cell numbers and examination of Giemsa stained smears. These assays showed that binding of the monoclonal antibody, in the presence of complement, both lysed and suppressed the proliferation of the T. annulata Hissar-infected cell line against which this monoclonal antibody was raised. This effect extended both to other (allogeneic) T. annulata Hissar-infected cell lines and to lymphoblastoid cell lines infected with other geographical stocks of T. annulata. An uninfected bovine lymphoid cell line was not affected by the antibody. The results obtained in these in vitro experiments are taken to mean that binding of the monoclonal antibody 4H5 to a T. annulata infection-associated antigen, in the presence of complement, will lyse and suppress specifically the proliferation of T. annulata-infected lymphoblastoid cells. These observations raise the possibility that immunization of cattle with the purified T. annulata infection-associated antigen recognized by this monoclonal antibody may provoke immune responses which are capable of suppressing the proliferation of T. annulata-infected lymphoblastoid cells in vivo and thus provide an effective method of immunoprophylaxis against tropical theileriosis. PMID- 3092169 TI - Immunoglobulin class specific responses to biochemically defined antigens of Trichinella spiralis. AB - A comparison of the humoral response to resistant (NIH) and susceptible (C3H) strains of mice, which reject adult worms at different rates during a primary infection, was made following infection with Trichinella spiralis. The serum concentration of immunoglobulins of the heavy chain classes IgM, IgG1, IgG2, IgG3 and IgA were determined by single radial immunodiffusion. Antibodies of the same immunoglobulin isotypes to biochemically defined, stage specific surface and secreted components of three stages of parasite development were also determined using an isotype specific immuno-coprecipitation assay. Independent variation of the responses of each immunoglobulin isotype was observed. The specific anti parasite response did not reflect total serum immunoglobulin levels in all immunoglobulin classes, and this is discussed in relation to basic mechanisms of immunoglobulin class switching. Finally a close correlation was observed in resistant (NIH) mice between the production of IgA antibody to surface components of adult worms and accelerated expulsion of this stage of the worm from the gastrointestinal tract. The possible relevance of this IgA response is further indicated by the failure of susceptible mice to synthesise IgA antibodies to the same surface antigens. PMID- 3092170 TI - Schistosoma mansoni from naturally infected Rattus rattus in Guadeloupe: identification, prevalence and enzyme polymorphism. AB - An enzymatic comparison has been made between isolates of Schistosoma mansoni from rats and humans in Guadeloupe and a Burundi isolate of S. rodhaini. Analyses of LDH, MDH, AcP, PGM, GPI, G6PDH and HK by isoelectric focusing provided no evidence for the involvement of S. rodhaini in the recent evolution of the schistosomes currently endemic in Guadeloupe. No distinction could be made between murine and human isolates of S. mansoni and it is suggested that murine schistosomiasis should not therefore be ignored in control programmes. Rattus rattus were captured at seven sites around the island; of 142 examined, 48 were positive for schistosomes. Differences in prevalence between habitats were marked and only small changes in prevalence were observed in localities sampled in 1982 and 1983. Animals with the greatest worm burdens were associated with areas of high prevalence, and age-related changes in worm burden were observed. Two alleles, a and b, at the MDH-1 locus of S. mansoni from rats were identified. Differences in the overall frequencies of these alleles were observed for schistosomes from different localities. Allelic frequencies representative of schistosomes from rats at four localities were stable from 1982 to 1983. The majority of positive animals, even those with light worm burdens, were found to be infected with a number of different schistosome genotypes. PMID- 3092172 TI - Maintenance of Theileria parva parva infection in an endemic area of Kenya. AB - The maintenance of Theileria parva parva infection in an endemic area of Kenya on the shore of Lake Victoria was studied in the field and laboratory. High prevalences of antibodies against T. parva and T. mutans and intra-erythrocytic piroplasms were detected in local zebu (Bos indicus) cattle. The mean infection rate of Theileria parasites in the tick, Rhipicephalus appendiculatus, in field collections was 1.1%. Most of the infection was attributed to T. parva parva by application of field ticks to susceptible cattle. Five cattle, all about 1.5 years old, were purchased from local owners and transported to the laboratory. All five had oscillating antibody titres against T. parva and T. mutans and had patent theilerial infections during the subsequent 13 months. Uninfected R. appendiculatus nymphs were applied to cattle at 0, 3, 6, 9 and 13 months after transport to Muguga, and 18 out of 23 batches transmitted T. parva parva infection to cattle when 100 resultant R. appendiculatus adults were applied. Infection rates in the tick batches were usually low, with 1 salivary gland acinus infected/tick. Hence, a frequent carrier state of naturally infected cattle has been demonstrated for T. parva parva for the first time, and it is likely that this carrier state is of great importance in maintenance of T. parva parva infection in the field. PMID- 3092171 TI - Attrition and temporal distribution of Schistosoma mansoni and S. haematobium schistosomula in laboratory mice. AB - The total number and distribution of schistosomula of Schistosoma mansoni and S. haematobium in all tissues and organs of mice from infection to 14-27 days was determined by compressed tissue autoradiography. Attrition of schistosomula, manifested as a decrease in the number of autoradiographic foci, was observed in organs other than the liver. Attrition commenced about 2 days after cercariae entered the skin, and conformed to a single exponential function with a rate constant (+/- standard error) of 7.0 +/- 0.5%/day for S. mansoni and 3.2 +/- 0.7%/day for S. haematobium. The temporal distribution of schistosomula of S. mansoni and S. haematobium differed quantitatively. In the case of S. mansoni, concomitant with a decrease in skin counts, the lung curve rose rapidly to a peak centred on day 6 and thereafter decreased more or less parallel to the total body curve. Significant accumulation in the liver was not observed until day 7, whereupon liver counts rose steadily to a plateau that extended from about day 14 to the end of the experiment and approximated the number of adult worms recovered from the hepatic portal vessels on day 42. A maximum of 26% and mean of 12% of all foci in the body were counted on autoradiograms of tissues other than the skin, lung and liver. The pelt averaged 14% of the body weight yet schistosomula were detected only in the area initially exposed to cercariae. The eviscerated carcass averaged 54% of the body weight yet contained only 0.8%-3.4% of the schistosomula during the period of accumulation in the liver. Between day 6 and day 14, the ratio of schistosomula in the pulmonary circulation to schistosomula in the systemic circulation did not remain constant, as would be the case if schistosomula circulated passively and randomly, but instead displayed a statistically significant decrease from 0.92 and 0.85. For these reasons, it was considered unlikely that schistosomula had circulated randomly and repeatedly through the pulmonary and systemic circulations and entered the hepatic portal system by chance as hypothesized by Miller & Wilson (1980). Instead it was considered more probable that schistosomula migrating from lungs to liver had followed a directed path through intervening vessels (Kruger, Heitman, van Wyk & McCully, 1969) or tissues (Wilks, 1967).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3092173 TI - [Prevention of functional and metabolic cardiac disorders in acute blood loss with gutimin]. PMID- 3092174 TI - Cromolyn sodium decreases the pulmonary vascular response to alveolar hypoxia in lambs. AB - We investigated the effect of cromolyn sodium, a mast cell stabilizing agent, on the pulmonary vascular response to alveolar hypoxia in six chronically instrumented lambs aged 9 to 11 days. Each lamb was instrumented on day 6 or 7 for measurements of systemic arterial, pulmonary arterial and left atrial pressures, and pulmonary blood flow. The animals were allowed to recover from surgery at least 3 days before they were studied. Each animal was studied twice, once with a cromolyn sodium infusion and once with a normal saline infusion (placebo). These paired experiments were separated by 24 h. Physiologic measurements were made during a 1-min predose control period, after an 8-min drug or placebo infusion, and after a 15-min period of alveolar hypoxia. Cromolyn sodium infusion alone did not affect baseline cardiovascular variables. Alveolar hypoxia following placebo infusion produced an increase in pulmonary arterial pressure and pulmonary vascular resistance; these responses were blocked in the animals given cromolyn sodium prior to induction of hypoxia. These results show that cromolyn sodium blocks the pulmonary vascular response to hypoxia and provide indirect evidence that mast cell degranulation, with subsequent release of vasoactive agents, mediates the pulmonary vascular response to hypoxia in newborn lambs. PMID- 3092175 TI - Ovarian function in girls with McCune-Albright syndrome. AB - We measured plasma estradiol levels and ovarian volumes in eight girls with precocious puberty due to McCune-Albright syndrome. Six girls had gonadotropin independent ovarian estrogen secretion and two girls had pubertal gonadotropin levels. Mean ovarian volume in all patients was significantly greater than in normal prepubertal girls. Mean ovarian volumes of the girls with McCune-Albright syndrome overlapped the range found in girls with idiopathic central precocious puberty or central precocious puberty associated with central nervous system lesions. However, the degree of asymmetry between the right and left ovaries was significantly greater in girls with McCune-Albright syndrome. Asymmetry was due, for the most part, to the presence of large solitary cysts in the larger of the two ovaries. In the six girls with McCune-Albright syndrome and gonadotropin independent precocious puberty, both mean ovarian volume and the degree of asymmetry between the right and left ovaries were significantly correlated with plasma estradiol. Serum follicle-stimulating hormone bioactivity was increased in two patients but did not vary with ovarian cyst size. Thyroid-stimulating hormone levels were normal but serum prolactin was slightly elevated in one of the six girls with gonadotropin-independent precocious puberty. Fluctuation in the size of unilateral ovarian cysts appears to result in changes in the plasma estradiol level, leading to advancement and spontaneous regression of secondary sexual characteristics and menses in girls with McCune-Albright syndrome. The cause of the cyst formation is unknown but may be related to periodic elevation of as yet undefined serum factors such as follicle-stimulating hormone bioactive substances. PMID- 3092176 TI - Prostaglandin synthetase inhibition in group B streptococcal shock: hematologic and hemodynamic effects. AB - A rabbit model of group B Streptococcal (GBS) shock was used to study the effects of prostaglandin synthetase inhibition on the hemodynamic and hematologic response to GBS shock. The infusion of heat-killed GBS in groups I and II produced significant decreases in mean arterial pressure, neutrophil counts, and platelet counts (p less than 0.05), and significant rises in concentrations of thromboxane B2 and 6-Keto-PGF1 alpha, the stable metabolites of thromboxane A2 and prostacyclin (p less than 0.05). Administration of indomethacin (4 mg/kg) after GBS infusion (group II) was associated with a significant rise in mean arterial pressure and a significant decline in thromboxane B2 and 6-Keto-PGF1 alpha concentrations (p less than 0.05) but had no effect on GBS-induced hematologic alterations. Indomethacin administration before GBS infusion (group III) prevented alterations in mean arterial pressure and was associated with a decrease in thromboxane B2 and 6-Keto-PGF1 alpha concentrations. Indomethacin in group III did not prevent neutropenia and thrombocytopenia and may have exacerbated neutropenia. Alteration of experimental GBS shock with prostaglandin synthetase inhibition produces disparate hemodynamic and hematologic response. PMID- 3092177 TI - Selective elevation of systemic blood pressure by epinephrine during sepsis induced pulmonary hypertension in piglets. AB - In a piglet model of group B beta Streptococci (GBS)-induced pulmonary hypertension, we have determined hemodynamic responses to epinephrine (EPI) infusion in both the systemic and pulmonary circulations. Three groups of piglets (GBS + EPI, n = 6; GBS + placebo, n = 6; placebo, n = 6) were studied. GBS, infused intravenously at approximately 5 X 10(7) organisms/kg/min, reduced cardiac index and stroke volume index while elevating pulmonary artery pressure and pulmonary vascular resistance index. Systemic vascular resistance index, heart rate and aortic pressure did not change during GBS infusion. Six piglets received intravenous EPI after cardiac index had fallen by 30% during GBS infusion. At 3.5, 7.0, and 15 micrograms/kg/min, respectively, EPI raised aortic pressure by 18.5, 31.0, and 45.0 mm Hg while EPI reduced pulmonary artery pressure by 5.2, 6.3, and 8.2 mm Hg. At each dose, EPI elevated systemic vascular resistance index and lowered pulmonary vascular resistance index. At 3.5 micrograms/kg/min, the elevation of aortic pressure was associated with an increase in both cardiac index and systemic vascular resistance index. At higher EPI doses, the rise in aortic pressure was accounted for entirely by an increase in systemic vascular resistance index. Systemic acid/base status and PaO2 did not differ among piglets who received GBS + EPI, GBS alone, or placebo. Extrapolation of these data to human infants must be approached with extreme caution. However, selective elevation of systemic blood pressure may be a feasible strategy for some infants to impede right-to-left shunting of blood often associated with sepsis-induced pulmonary hypertension. PMID- 3092178 TI - Optimal constant positive airway pressure assessed by arterial alveolar difference for CO2 in hyaline membrane disease. AB - In a group of infants with hyaline membrane disease, the level of optimal constant positive airway pressure (CPAP) was assessed by raising CPAP in small steps from an initial low value, and after each change measuring the arterial alveolar difference for CO2 (aADCO2) and transmission of airway pressure to the esophagus. Below optimal CPAP there was a progressive increase in mixed alveolar partial pressure of CO2 (PACO2) and no change in arterial partial pressure of CO2 (PaCO2), so that aADCO2 declined and reached a lowest value at optimal CPAP. Correspondingly, transmission of airway pressure increased progressively and reached a highest value at optimal CPAP. Between 1 step below and optimal CPAP, PACO2 rose from 30.9 to 34.0 torr, and aADCO2 declined from 16.6 to 12.7 torr. Between optimal and 1 step above optimal CPAP, PaCO2 increased from 46.7 to 51.0 torr, PACO2 rose slightly, and aADCO2 increased from 12.7 to 15.6 torr. Thus, the aADCO2 was an excellent index of optimal CPAP. In five patients with measurements of PaO2 at constant fractional inspired oxygen, calculated values for arterial oxygen saturation changed from 80.8 to 91.5 to 92.2%, and calculated values for venous admixture changed from 0.61 to 0.48 to 0.46 as CPAP was raised from 1 step below through optimal to 1 step above optimal CPAP. The results are interpreted to mean a progressive improvement in perfusion of well ventilated lung units as CPAP increased to optimal levels, but a significant reduction of both ventilation and perfusion above optimal CPAP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092180 TI - American Academy of Pediatrics Committee on Children with Disabilities: Transition of severely disabled children from hospital or chronic care facilities to the community. PMID- 3092179 TI - Pharyngeal culturing and reporting of pediatric gonorrhea in Connecticut. PMID- 3092181 TI - Depression: a disorder of timekeeping? PMID- 3092182 TI - The prevalence of encephalitozoonosis in Danish farmed foxes. AB - The prevalence of Encephalitozoonosis in Danish farmed foxes variated between 3.0% and 73.8% with an average of 19.3%. The prevalence was at little higher in silver foxes than in blue foxes. It seemed, that the titers variated in relation to the sexual period with the maximum value in the oestrus. PMID- 3092183 TI - Sequence and expression of the Cc gene, a member of the dopa decarboxylase gene cluster of Drosophila: possible translational regulation. AB - A transcript has been localized proximal to the dopa decarboxylase (Ddc) gene within a cluster of genes involved in cuticle formation and catecholamine metabolism in Drosophila. This gene, which has been identified as I(2)37Cc, maps 2.0kb from the 5' end of the Ddc gene and is transcribed in the same direction as Ddc. We describe a new deficiency which in conjunction with previous deficiencies localizes the I(2)37Cb and I(2)37Cc loci to the cytogenetic interval 5' to Ddc. We present the sequence of the Cc gene and corresponding cDNA. The Cc message contains several open reading frames 5' to the large open reading frame responsible for the lethal complementation group, suggesting that expression of Cc function may be regulated translationally. The Cc transcript is expressed in early embryos, late embryos, late third instar larvae and adults. We discuss the implications of these findings with respect to the gene organization in the region. PMID- 3092184 TI - Conservation of sequences adjacent to the telomeric C4A2 repeats of ciliate macronuclear ribosomal RNA gene molecules. AB - We sequenced and compared the telomeric regions of linear rDNAs from vegetative macronuclei of several ciliates in the suborder Tetrahymenina. All telomeres consisted of tandemly repeated C4A2 sequences, including the 5' telomere of the 11 kb rDNA from developing macronuclei of Tetrahymena thermophila. Our sequence of the 11 kb 5' telomeric region shows that each one of a previously described pair of inverted repeats flanking the micronuclear rDNA (Yao et al., Mol. Cell. Biol. 5: 1260-1267, 1985) is 29 bp away from the positions to which telomeric C4A2 repeats are joined to the ends of excised 11 kb rDNA. In general we found that the macronuclear rDNA sequences adjacent to C4A2 repeats are not highly conserved. However, in the non-palindromic rDNA of Glaucoma, we identified a single copy of a conserved sequence, repeated in inverted orientation in Tetrahymena spp., which all form palindromic rDNAs. We propose that this sequence is required for a step in rDNA excision common to both Tetrahymena and Glaucoma. PMID- 3092185 TI - Transient expression of Drosophila melanogaster rDNA promoter into cultured Drosophila cells. AB - Recombinant plasmids that carry the bacterial CAT gene under the transcriptional control of the D. melanogaster rDNA promoter have been introduced by transfection into cultured Schneider II Drosophila cells and their template activity followed at the RNA and protein level. While no CAT enzyme activity is measurable 48 hrs after transfection, high levels of hybrid rRNA-CAT transcripts that originate at the authentic rRNA start site are detected by S1 mapping analysis. The interval 180/+34 of a rDNA transcriptional unit is sufficient to ensure faithful polymerase I transcription. However, the presence of a complete NTS (non transcribed spacer) region greatly enhances the transcriptional activity of exogenously added rDNA templates. Competition experiments between constructs carrying different amounts of NTS sequences indicate that spacer segments confer a transcriptional advantage efficiently attracting necessary transcription factors and/or polymerase I molecules. PMID- 3092186 TI - B-lymphocyte targeting of gene expression in transgenic mice with the immunoglobulin heavy-chain enhancer. AB - A hybrid gene containing rabbit beta-globin structural sequences (-9 to +1650), and a chicken conalbumin gene promoter (+62 to -102) in the place of the beta globin promoter (upstream from -9), was inactive in 5 different transgenic mouse line. Adding the mouse immunoglobulin heavy-chain (IgH) enhancer to this construction specifically stimulated expression in B-cells. These results show that IgH enhancer is specifically active in B-cells. Expression of the hybrid gene was low compared to the endogenous immunoglobulin heavy and light-chain genes. Substituting the mouse immunoglobulin kappa light-chain gene (Ig kappa) promoter (+4 to -800) for the heterologous conalbumin promoter was not sufficient to restore gene expression to level of the endogenous genes. In addition to the reproducible B cell expression, we also found inheritable unexpected expression in certain tissues, which varied from line to line. PMID- 3092187 TI - Drosophila ARSs contain the yeast ARS consensus sequence and a replication enhancer. AB - A number of restriction fragments that function as autonomously replicating sequences (ARSs) in yeast have been isolated from Drosophila melanogaster DNA. The behaviour in yeast of plasmids containing Drosophila ARS elements was studied and compared to that exhibited by the archetypal yeast ARS-1 plasmid. ARS functions were localised by subcloning and BAL-31 deletion analysis. These studies demonstrated the structural and functional complexity of Drosophila ARSs. Each Drosophila ARS element has at least two domains, one essential for replication (the replication sequence, RS) and a second (the replication enhancer, RE) which is essential for maximum function of the RS. The RS of three Drosophila ARSs was shown to contain a sequence identical to an 11 bp yeast ARS consensus sequence (5' A/T TTTATPuTTT A/T 3'). These observations lend support to the hypothesis that heterologous ARS elements may be of biological significance. PMID- 3092188 TI - Quantitative analysis of the relationship between nucleotide sequence and functional activity. AB - Matrices can be used to evaluate sequences for functional activity. Multiple regression can solve for the matrix that gives the best fit between sequence evaluations and quantitative activities. This analysis shows that the best model for context effects on suppression by su2 involves primarily the two nucleotides 3' to the amber codon, and that their contributions are independent and additive. Context effects on 2AP mutagenesis also involve the two nucleotides 3' to the 2AP insertion, but their effects are not independent. In a construct for producing beta-galactosidase, the effects on translational yields of the tri-nucleotide 5' to the initiation codon are dependent on the entire triplet. Models based on these quantitative results are presented for each of the examples. PMID- 3092191 TI - The young chronic client in mental health today. AB - Due to the nature of the work with this demanding population, who, in spite of all efforts, demonstrates only minimal changes at best, nurses need aggressive management of their own lives. Burnout is rampant. Work with this type of client is not for everyone. Programs need to offer staff the opportunity to work with these clients only if the staff is capable and desires the challenge. It is necessary to set realistic goals and expectations with clients and to learn to accept tiny changes. Nurses must help the client become more realistic in their expectations of what will be achieved. It is important to note that the therapist may scare the client into regressed behavior by being too hopeful, by pushing them too far too fast, and by allowing them to go too fast. Caution should be taken with respect to encouragement and expectations of normalcy. If goals are too high and the client "fails," the therapist perceives that he/she is the one who failed. The patient who manages to achieve a level of functioning that enables him to interface with the outside often finds a world that is cold, demanding, and cruel--one that is easier to escape from than to deal with. One must be flexible and accessible to the client--involved with honest detachment. For the nurse therapist to serve this population requires sophistication in the theories of child and adolescent suicide, crisis intervention, aggression management, chemical abuse and use, and the ability to negotiate housing, money, food, services--things which have previously been the domain of others.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092190 TI - Complexity of ambulatory care: nurse practitioner and physician caseloads. AB - The case mix of patient caseloads of nurse practitioners (NPs), faculty attending physicians (F/MDs), and resident housestaff in an inner-city teaching hospital was examined. Social and demographic variables as well as diagnoses, medications, risks, and functional status were used to define complexity. Charts of 111 patients (37 per group) were analyzed. Patients of NPs and F/MDs were essentially equally complex, but residents' patients were somewhat less complicated. Differences in styles of practice were seen, with NPs attending more to symptoms of nonpathological conditions, comfort, and comprehensiveness of care. Scope of practice, complexity, and system of care are suggested as important variables to consider in future studies of NPs and in studies relating case mix to productivity and resource consumption. PMID- 3092192 TI - [Advances in endocrinology. Problems of low stature]. PMID- 3092189 TI - Sigma factors from E. coli, B. subtilis, phage SP01, and phage T4 are homologous proteins. AB - We show, using dot matrix comparisons and statistical analysis of sequence alignments, that seven sequenced sigma factors, E. coli sigma-70 and sigma-32, B. subtilis sigma-43 and sigma-29, phage SP01 gene products 28 and 34, and phage T4 gene product 55, comprise a homologous family of proteins. Sigma-70, sigma-32, and sigma-43 each have two copies of a sequence similar to the helix-turn-helix DNA binding motif seen in CRP, and lambda repressor and cro proteins. B. subtilis sigma-29, SP01 gp28, and SP01 gp34 have at least one copy similar to this sequence. We propose that a second sequence, conserved in all seven proteins is the core RNA polymerase binding site. A third region, present only in sigma-70 and sigma-43, may also be involved in interaction with core. Available mutational evidence supports our model for sigma factor structure. PMID- 3092193 TI - Growth hormone releasing hormone stimulates the release of gastrin in rat. AB - The inhibitory effect of somatostatin on gastrin release is well known. Could the growth hormone releasing hormone (GHRH), an antagonist of somatostatin on growth hormone (GH) release, have a gastrin-releasing effect on gastrin? To answer this question, two types of experiments were conducted: (1) The study of the effect of GHRH on gastrin in rats, which showed a significant and dose related release for the three doses studied: 0.12, 0.6 and 3.0 micrograms/rat. (2) The study on the recurrence of this gastrin releasing effect which has been found to be significant (1 to 5 injections at 1 hour intervals). Our data suggest that GHRH is an hypothalamic releasing factor for gastrin release. Accordingly, gastrin may mediate the observed proliferative effect of GHRH in the upper digestive tract. PMID- 3092194 TI - Effect of rGRF on exocrine pancreatic secretion of the rat in vivo. AB - Human and rat GRFs have been reported to stimulate cAMP production and amylase release by guinea pig acinar cells in vitro, with different potencies. Previous reports indicated that hGRF had no effect on pancreatic secretion of the rat in vivo. In the present experiments, dose-response studies were made with rGRF, VIP and secretin on the pancreatic secretion of anaesthetized rats. All three peptides stimulated pancreatic secretion. rGRF induced a slight water and electrolyte secretion, with an efficacy about ten times smaller than secretin, and a potency about thirty times smaller. rGRF stimulated total protein output with the same efficacy as secretin and VIP, and with the same potency as VIP, that is about 100 times smaller than secretin. rGRF increased the concentration of total protein, but not that of bicarbonate in pancreatic juice. Maximal doses of VIP and rGRF did not show any additive effect. It is concluded that large doses of rGRF are able to stimulate the rat acinar cells in vivo, presumably through an interaction with VIP receptors. PMID- 3092195 TI - The glucagon superfamily: precursor structure and gene organization. AB - The glucagon superfamily includes the polypeptides glucagon, secretin, vasoactive inhibitory peptide (VIP), gastric inhibitory peptide and growth hormone-releasing factor (GHRF). Complementary DNA clones which encode the precursors to glucagon, VIP and GHRF have been isolated. Although the sizes and sequences of preproglucagon, prepro VIP and preproGHRF are distinct, the structural organization of the three precursors is similar. Each has a signal peptide, an NH2-terminal peptide and one, two or three peptides whose sequences are related to glucagon. Prepro VIP and preproGHRF also have a COOH-terminal peptide. The sequences of two different anglerfish preproglucagon molecules have been determined and they contain the sequences of glucagon and a related peptide. In contrast, hamster, cow and rat preproglucagon contain the sequences of glucagon and two related peptides. Human and rat prepro VIP contain the sequences of VIP and the related peptide PHM/PHI-27. Human and rat preproGHRF contain the sequence of only one peptide related to glucagon, i.e., GHRF. The genes for both preproglucagon and preproGHRF have been isolated. Their exon-intron organization indicates that each exon encodes a functionally distinct region of the precursor and mRNA. PMID- 3092196 TI - Clinical studies with human growth hormone releasing factor in normal adults and patients. AB - The recent availability of human growth hormone releasing factor (hGRF) encouraged thorough investigations of human growth hormone secretion. Moreover it is now possible to put forward a therapeutic application for this hormone. Herein, we report the dose-effect relationship obtained between hGRF and GH response in normal young men submitted to IV administration of doses ranging from 2.5 to 600 micrograms per subject, in three protocols. In some subjects the 2.5 micrograms dose elicited GH secretion as compared with placebo. A highly significant dose-effect was observed (based on GH-AUC and GH-peak) for doses ranging from 5 to 80 micrograms. Responses were identical above 80 micrograms. We conclude that the optimal dose required to elicit maximum GH release with minimal unwanted effects is 80 micrograms in adults. These are related to the dose and observed for doses up to 80-150 micrograms. Subcutaneous administration also induced GH-release, with relationship to the doses used (100, 300 and 600 micrograms per subject). The mean response to the highest dose (600 micrograms) was comparable in timing and magnitude to that obtained with a 100 microgram intravenous dose. Bioactivity of GH released under hGRF was proven in the Nb2 lymphoma cell multiplication assay and a high correlation was obtained between bioassay and radioimmunoassay. GH was present in blood after hGRF under 3 molecular forms corresponding to little, big and big-big GH with percentages of 50, 30 and 20, respectively. An early and slight increase in prolactin was found to be related to the hGRF doses above 80 micrograms. No change was observed for doses less than 80 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092197 TI - Strategies in the design of synthetic agonists and antagonists of growth hormone releasing factor. AB - Previous research on the favorable effects of mild conformational restriction in the N-terminal region of glucagon has led us to carry out analogue studies on the sequence-related 1-12 region of GRF(1-29)NH2. Replacement of each of the first 11 amino acids by its D-isomer in turn gave a total of 5 analogues exhibiting increases in potency. Other analogues containing multiple D-amino acid replacements were also examined and found to be highly potent, for instance: D Tyr-1,D-Ala-2, 2630; His-1,D-Ala-2, 3440; Ac-His-1,D-Ala-2, 1574; D-Ala-2,Nle-27, 1840; D-Ala-2,D-Asn-8,Nle-27, 1580; D-Ala-2,D-Asp-3,D-Asn-8,Nle-27, 2000; D-Asp 3,D-Asn-8,Nle-27, 3810 (GRF(1-29) = 100%). It is possible that these results with D-isomers reflect the presence of reverse turns (beta-bends) in this region of GRF. Indeed, the qualitative predictive method of Chou and Fasman supports this theory and indicates reverse turns in the 1-5 and 6-10 sequences. Further studies were performed to test this hypothesis by introducing even more rigidity into the N-terminal region via disulfide bond formation between positions normally containing aromatic amino acids. None of the bridged peptides displayed biological activity which suggests that chain folding does not produce any proximity among N-terminal residues. We had shown previously that position 2(Ala) was extremely sensitive to both conformational and side-chain alterations. This observation was extended to analogues containing Sar and Pro, both of which were also inactive on GH release at the doses tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092199 TI - Tegaful photosensitivity--lichenoid and eczematous types. PMID- 3092198 TI - New analogues of secretin. AB - For the evaluation of structure/activity relationships, some porcine secretin analogues, modified in the N-terminus, have been synthesized by segment condensation in solution. The secretin activity of the analogues was defined as the volume of pancreatic juice secreted in rats and dogs. The exchange of the N terminal pentapeptide for the N-terminal pentapeptide of human somatotropin releasing factor (h-SRF) resulted in a peptide ([1-Tyr,2,4-Di-Ala,5-Ile]secretin) with practically no SRF-activity (less than 1% SRF-activity up to 100 micrograms/kg in the rat), but surprisingly high secretin activity (almost 100% in the rat, but only 1150 CU/mg (27%) in the dog). [3-L-Cysteic acid]secretin showed 1750 CU/mg (39%) in the dog, but a less activity (23%) in the rat. [6-D Phe]secretin and [5-D-allo-Thr]secretin are again strongly species specific. They exhibited an activity of less than 1% in the dog, but about 10-15% in the rat. The smallest secretin activity was observed with [1-Cys,6-Cys]secretin in the oxidized form. The activity in the rat with this analogue was only about 0.2%. PMID- 3092200 TI - A morphological and immunohistochemical study of phytophotodermatitis-like bullae induced by PUVA. PMID- 3092201 TI - [Myeloblastic leukemia in IgG lambda multiple myeloma]. PMID- 3092202 TI - Comparative studies on the amino acid derivatives of indometacin. AB - A series of amino acid derivatives of indometacin (IND) was investigated in regard to their protein binding and prostaglandin synthetase inhibition in vitro, and to acute toxicity, anti-inflammatory, antiedemic, analgesic actions, and the influence on the central nervous system in vivo. In biochemical tests the compounds were several times less potent than IND. They differed among themselves in the respect of toxicity, which was always much lower than that of IND. Out of eight compounds investigated N-IND-glycine (K1) and N-IND-epsilon-aminocaproic acid (K5) exerted more favorable antiedemic and analgesic action than IND did. Both the derivatives only weakly inhibited the cotton-pellet granuloma formation. K1 acted similarly to IND in the arthritis test. K1, K5 and IND similarly irritated the gastric mucosa. A modification of IND structure by introduction of glycine or epsilon-aminocaproic acid resulted in two new anti-inflammatory agents of more favorable therapeutic index in the antiedemic and analgesic action and of much lower toxicity than the reference compound. PMID- 3092203 TI - An on-farm method for determination of sulfonamide drug residues in turkeys. 1. An agar-diffusion analysis for sulfadimethoxine in whole blood. AB - A simple and inexpensive sulfonamide-screening test was evaluated using turkeys. An agar-diffusion procedure was developed to estimate the levels of sulfonamides in the edible tissues of turkeys by determining the drug level in whole blood. The analysis was adapted for use on whole blood that was easily collected from live birds on the farm with minimal equipment and skill. This Whole Blood Sulfa Test (WBST) was quantified by the use of a standard curve and was successfully applied to on-farm use in the Pacific Northwest. Agar plates were prepared using fortified Mueller-Hinton medium. Bacillus megaterium spores were applied to the agar to form confluent growth, and paper discs (10 mm) were laid onto the agar. Whole blood was collected from commercial turkeys prior to marketing, and the blood was immediately applied to the test paper discs. After incubation, blood that contained sulfa inhibited bacterial growth around the disc, and the clear zones of inhibition were measured. The WBST was consistently accurate to 1.22 ppm, and sulfa levels were detected as low as .04 ppm. Results were attained in 12 hr and were relatively inexpensive at $3.00/test/flock. PMID- 3092204 TI - Canthaxanthin as a model for the study of utilization of oxycarotenoids by chickens. AB - A white corn-soy diet amended with varying levels (0, 5, 10, 20, 40, and 80 ppm) of canthaxanthin, a red diketocarotenoid available by chemical synthesis, and fed to young broiler chickens for 3 weeks has the attributes of a useful experimental model for the study of absorption, transport, and deposition of oxycarotenoids. On high pressure liquid chromatography of extracts of the diet and tissues of the birds, canthaxanthin predominated over the background level of nonspecific carotenoids. The concentrations of canthaxanthin found in the contents of the jejunum and large intestine and in the serum, liver, and toe web were directly proportional to the dietary concentration. Departure from such linear relationships would signal loci of action for factors affecting pigmentation. Analysis of toe webs, an integumentary depot site for carotenoids, revealed that the concentrations of canthaxanthin and two other compounds, one more polar and the other less polar than canthaxanthin, were proportional to the dietary concentration of canthaxanthin. Saponification converted the less polar compound to the more polar compound. The behavior of these compounds in response to dietary canthaxanthin, to chromatography, and to saponification can be explained by assuming that canthaxanthin, a diketocarotenoid, was partly reduced to a ketohydroxy carotenoid (hydroxyechinenone) whose hydroxyl group is acylated to form an ester. These products represent new metabolic reactions in poultry. PMID- 3092205 TI - The diagnosis and management of asthma in childhood. PMID- 3092206 TI - Prenatal diagnosis of non-ketotic hyperglycinemia. AB - We describe successful prenatal diagnosis in four pregnancies at risk for non ketotic hyperglycinemia, two affected and two unaffected, using the glycine level and the glycine/serine ratio in amniotic fluid obtained at 16 weeks gestational age. Although this method of prenatal diagnosis for non-ketotic hyperglycinemia has been effective in our hands the narrow differences between affected and unaffected pregnancies indicate the need for caution concerning its reliability. PMID- 3092207 TI - Partial purification and characterization of feline gamma-like interferon. AB - Feline interferon (IFN) was produced from spleen cells stimulated by Staphylococcus enterotoxin A (SEA). The IFN was purified by a three-step procedure using controlled pore glass adsorption chromatography, concanavalin A (ConA)-agarose column chromatography and gel filtration. The final product of these procedures which had activity of an IFN appeared as a single peak of activity with molecular weight of approximately 50,000. It was sensitive to acid and heat, suggesting that the isolated material was a gamma IFN. The total recovery of feline gamma IFN was 8.2%. Specific activity was 2.95 X 10(4) unit/micrograms protein and was concentrated 2.8 X 10(4) times. This preparation of purified feline gamma IFN was destroyed completely by 0.1% sodium dodecyl sulfate within 20 min. As an inducer of feline gamma IFN, SEA appeared to produce a more uniform IFN product than did ConA. Further, the presence of 10% ethylene glycol in the sample applied to ConA-agarose column as well as its absence in the elution buffer was effective in reducing contaminating acid- and heat-resistant IFNs in the preparation. PMID- 3092208 TI - [Characteristics of morphological changes in the lungs of guinea pigs after administration of ultra-small forms of Mycobacteria obtained from patients with tuberculosis]. PMID- 3092209 TI - [Comparative therapeutic activity of rifampicin and isoniazid in different densities of microbial population in the lungs of experimental animals]. PMID- 3092210 TI - [Effect of streptococcal and staphylococcal infections on the course of experimental tuberculosis]. PMID- 3092211 TI - [A standardized highly sensitive variant of the complement fixation test for the detection of anti-tuberculosis antibodies]. PMID- 3092212 TI - Nucleotide sequence of the myxobacterial hemagglutinin gene contains four homologous domains. AB - Myxococcus xanthus, a Gram-negative bacterium, has a complex life cycle that includes fruiting-body formation, a primitive form of multicellular development. Myxobacterial hemagglutinin (MBHA) is a lectin that is induced during the aggregation phase of fruiting-body formation. We have cloned the gene for MBHA and determined its sequence by the dideoxy chain-termination technique. The sequence data show the probable sites for translational initiation and termination and suggest that MBHA does not contain a cleaved leader signal peptide. The DNA sequence shows four strong internal homologies. The deduced amino acid sequence shows that the protein (Mr 27,920) consists of four highly conserved domains each consisting of 67 amino acids. Thus MBHA is physically multivalent in structure, a requirement for all hemagglutinins. PMID- 3092213 TI - p21 ras proteins and guanine nucleotides modulate the phosphorylation of 36- and 17-kilodalton mitochondria-associated proteins. AB - We have found that, when isolated rat liver mitochondria are incubated with [gamma-32P]ATP, there is phosphorylation of 36- and 17-kDa proteins. These proteins together with their protein kinase(s) are released as a complex by incubation of the isolated rat liver mitochondria at 20 degrees C for 30 min with 10 mM glucose 6-phosphate, 0.5 mM inositol phosphate, or 0.01 mM inositol triphosphate. Phosphorylation of the 36- and 17-kDa proteins in this soluble protein fraction is modulated by p21 proteins encoded by ras oncogenes and synthesized in Escherichia coli via recombinant DNA methods. A normal p21 ras protein stimulates phosphorylation of the 36-kDa protein and inhibits phosphorylation of the 17-kDa protein, whereas two transforming p21 ras proteins inhibit phosphorylation of both the 36- and 17-kDa proteins. Although GDP and 5' guanylyl imidodiphosphate also influence the phosphorylation of these proteins, we present evidence that the effects of p21 ras protein are not simply due to their bound GDP. This novel system may be useful for further studies on the biochemical functions of the p21 ras proteins. PMID- 3092214 TI - cDNA clones encoding murine IgE-binding factors represent multiple structural variants of intracisternal A-particle genes. AB - Previously [Moore, K. W., Jardieu, P., Mietz, J. A., Trounstine, M. L., Kuff, E. L., Ishizaka, K. & Martens, C. L. (1986) J. Immunol. 136, 4283-4290], we examined a T-hybridoma-derived cDNA clone, 8.3, that encodes a biologically active murine IgE-binding factor (IgE-BF), and we showed that it was a variant member of the endogenous retroviral gene family related to mouse intracisternal A particles (IAPs). We have now characterized four more IgE-BF cDNA clones by heteroduplex and restriction enzyme analysis and found that they all represent different structural variants of the full-size IAP genomic element. In clones 8.3 and 10.2, which have been fully sequenced, the open reading frames span deletions 3.4 and 1.9 kilobases (kb) long, respectively, and specify different gag-pol fusion polypeptides. Clone 9.5 contains a 2.1-kb deletion entirely within the pol region. Two other clones (4.2 and 11.7) contain no internal deletion and may represent truncated cDNA copies of full-size (7.2 kb) IAP gene transcripts. Structural variants very similar to clone 10.2 are common in the mouse genome, and clone 9.5 is also probably not a unique gene form. The sequences of clones 8.3 and 10.2 are different in detail, but each is closely homologous to a randomly cloned mouse genomic IAP element throughout the gag-related portions of their open reading frames. Antibodies against two oligopeptides specified by the sequence of clone 8.3 immunoprecipitated IAP-related proteins from mouse neuroblastoma and myeloma cells, confirming that the IgE-BF produced by this clone shares sequence with expressed IAP elements in different cell types. Thus, information related to the IgE-BF is an integral part of the murine IAP retrotransposon gag gene. PMID- 3092216 TI - Cloning and DNA sequence analysis of the cDNA for the precursor of the beta chain of bovine follicle stimulating hormone. AB - Follicle stimulating hormone (FSH) plays essential roles in the maintenance and development of oocytes and spermatozoa in normal reproductive physiology. FSH possesses two subunits, alpha and beta, the latter being responsible for FSH biological specificity. We have cloned and sequenced the cDNA encoding the FSH beta chain from a bovine anterior pituitary cDNA library. The mature molecule is 109 amino acids long and is preceded by a 20-amino acid putative signal peptide. RNA gel blot analysis of bovine pituitary RNA shows that the mRNA encoding beta chain of FSH is approximately 1.7 kilobases in length. PMID- 3092215 TI - Human thymocytes bind to autologous and allogeneic thymic epithelial cells in vitro. AB - The thymus plays a critical role in the generation of immunocompetent T lymphocytes. In the thymus, lymphocytes are in close contact with epithelial cells, and this contact is necessary for T-cell maturation. Using cultured human thymic epithelial (TE) cells, we have found that human thymocytes bind to human TE cells in vitro. Thymocytes bound to both allogeneic and autologous TE cells and to the epidermoid carcinoma cell line A431 but did not bind to epidermal keratinocytes or to thymic fibroblasts. Thymocyte binding to TE cells was trypsin and cytochalasin B-sensitive. Indirect immunofluorescence assays showed that both mature (T6-, T3+) and immature (T6+, T3-) thymocytes bound TE cells. In our system, TE-thymocyte binding was not inhibited by antibodies to class I or class II major histocompatibility antigens. In vitro binding of thymocytes to TE cells may represent a correlate of in vivo TE-thymocyte interactions and provides a model system for the study of human intrathymic T-lymphocyte maturation and activation. PMID- 3092217 TI - Genetic-molecular basis for a simple Drosophila melanogaster somatic system that detects environmental mutagens. AB - We have developed a simple, objectively scorable test for the mutagenicity of chemical compounds which can be fed Drosophila melanogaster. The test depends upon the somatic reversion of the X chromosome, recessive eye color mutation, white-ivory (wi) to wild type (w+). Reversions are scored as clones of w+ facets in the wi eyes of eclosing adults. To increase the sensitivity, a tandem quadruplication containing four wi mutations was synthesized. Thus, in homozygous females eight wi mutations are potentially revertible. Six mutagenic compounds, all alkylating agents, all gave positive results at several concentrations tested. Molecular analysis demonstrates that the induced reversions, germinal and somatic, are associated with the loss of 2.9-kilobase DNA duplicated in the wi mutation. PMID- 3092218 TI - Inhibitory and stimulatory G proteins of adenylate cyclase: cDNA and amino acid sequences of the alpha chains. AB - The G protein family of signal transducers includes five heterotrimers, which are most clearly distinguished by their different alpha chains. The family includes Gs and Gi, the stimulatory and inhibitory GTP-binding regulators of adenylate cyclase; Go, a protein of unknown function abundant in brain; and transducin 1 and transducin 2, proteins involved in retinal phototransduction. Using a bovine alpha t1 cDNA as a hybridization probe, we have isolated mouse cDNAs that encode alpha chains of two G proteins. One encodes a polypeptide of 377 amino acids (Mr 43,856), identified as alpha s because it specifically fails to hybridize with any transcript in an alpha s-deficient S49 mouse lymphoma mutant, cyc-; the other encodes a polypeptide of 355 amino acids (Mr 40,482), presumed to be alpha i. These alpha chains and those of the retinal transducins exhibit impressive sequence homology. Of the four, alpha t1 and alpha t2 are most alike (81% identical amino acid residues), whereas the presumptive alpha i is more similar than alpha s to alpha t1 (63% vs. 38% identical residues). Sequence homologies with p21ras and elongation factor Tu identify regions of the alpha chains that form the site for GTP binding and hydrolysis. Further comparison of the alpha chain sequences suggests additional regions that may contribute to interactions with beta gamma subunits and the receptor and effector components of different signal transduction systems. PMID- 3092220 TI - Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin. AB - Coagulation factor V is a high molecular weight plasma glycoprotein that participates as a cofactor in the conversion of prothrombin to thrombin by factor Xa. A phage lambda gt11 Hep G2 cell cDNA expression library was screened by using an affinity-purified antibody to human factor V, and 11 positive clones were isolated and plaque-purified. The clone containing the largest cDNA insert contained 2970 nucleotides and coded for 938 amino acids, a stop codon, and 155 nucleotides of 3' noncoding sequence including a poly(A) tail. The coding region includes 651 amino acids from the carboxyl terminus that constitute the light chain of human factor Va and 287 amino acids that are part of the connecting region of the protein. The predicted amino acid sequence agreed completely with 147 amino acid residues that were identified by Edman degradation of cyanogen bromide peptides isolated from the light chain. During the activation of factor V, several peptide bonds are cleaved by thrombin, giving rise to a heavy chain, a connecting fragment(s), and a light chain. The light chain is generated by the cleavage of an Arg-Ser peptide bond. The amino acid sequence of the light chain is homologous (40%) with the carboxyl-terminal fragment (Mr, 73,000) of human factor VIII. Both fragments have a similar domain structure that includes a single ceruloplasmin-related domain followed by two C domains. The carboxyl terminus of the connecting region, however, shows no significant amino acid sequence homology with factor VIII. It is very acidic and contains a number of potential N-linked glycosylation sites. It also contains about 20 tandem repeats of nine amino acids. PMID- 3092219 TI - Cloning and sequence of a cDNA coding for the human beta-migrating endothelial cell-type plasminogen activator inhibitor. AB - A lambda gt11 expression library containing cDNA inserts prepared from human placental mRNA was screened immunologically using an antibody probe developed against the beta-migrating plasminogen activator inhibitor (beta-PAI) purified from cultured bovine aortic endothelial cells. Thirty-four positive clones were isolated after screening 7 X 10(5) phages. Three clones (lambda 1.2, lambda 3, and lambda 9.2) were randomly picked and further characterized. These contained inserts 1.9, 3.0, and 1.9 kilobases (kb) long, respectively. Escherichia coli lysogenic for lambda 9.2, but not for lambda gt11, produced a fusion protein of 180 kDa that was recognized by affinity-purified antibodies against the bovine aortic endothelial cell beta-PAI and had beta-PAI activity when analyzed by reverse fibrin autography. The largest cDNA insert was sequenced and shown to be 2944 base pairs (bp) long. It has a large 3' untranslated region [1788 bp, excluding the poly(A) tail] and contains the entire coding region of the mature protein but lacks the initiation codon and part of the signal peptide coding region at the 5' terminus. The two clones carrying the 1.9-kb cDNA inserts were partially sequenced and shown to be identical to the 3.0-kb cDNA except that they were truncated, lacking much of the 3' untranslated region. Blot hybridization analysis of electrophoretically fractionated RNA from the human fibrosarcoma cell line HT-1080 was performed using the 3.0-kb cDNA as hybridization probe. Two distinct transcripts, 2.2 and 3.0 kb, were detected, suggesting that the 1.9-kb cDNA may have been copied from the shorter RNA transcript. The amino acid sequence deduced from the cDNA was aligned with the NH2-terminal sequence of the human beta-PAI. Based on this alignment, the mature human beta-PAI is 379 amino acids long and contains an NH2-terminal valine. The deduced amino acid sequence has extensive (30%) homology with alpha 1-antitrypsin and antithrombin III, indicating that the beta-PAI is a member of the serine proteinase inhibitor (serpin) superfamily. PMID- 3092221 TI - High rate of somatic point mutation in vitro in and near the variable-region segment of an immunoglobulin heavy chain gene. AB - The "silent" allele at the immunoglobulin heavy-chain locus in the pre-B lymphocyte line 18-81 contains a correctly assembled gene. However, an amber termination codon within the variable-region gene segment prematurely terminates translation into complete heavy chain. Revertants that do produce heavy chain are generated at a high rate, which is termed hypermutation. By DNA sequencing of subclones, we have confirmed that whenever mu chain is produced by the usually silent allele, a true reversion is found in the DNA. Mutations are not confined to the position of the amber termination codon but are also found at other sites in and near the variable-region gene segment. PMID- 3092222 TI - A role for T3+4-6-8- transitional thymocytes in the differentiation of mature and functional T cells from human prothymocytes. AB - In vivo, immunocompetent T lymphocytes are only detected late in ontogeny, among mature thymocytes expressing either T4 (L3T4 in mouse) or T8 (Lyt-2) surface glycoproteins. We have previously shown, however, that there are functional precursors among T3+4-6-8- human thymocytes in vivo. Here we report on the in vitro differentiation of prothymocytes into T3+4-6-8- and mature T cells. T11+3-4 6-8- prothymocytes (0.5% of total thymocytes, greater than 98% pure) were obtained after treatment of thymocytes with OKT3 (T3), OKT4A (T4), Na1/34 (T6), and B9.4 (T8) monoclonal antibodies plus complement. During culture, the prothymocyte precursors acquire first T3 and then either T4 or T8, but not T6. The largest subpopulation in the thymus, T4+6+8+ cells, are not detected among the in vitro T-cell precursors. During culture, the precursors acquire cytolytic activity as soon as they express either the T3+4-6-8- or the mature (T3+4+8- or T3+4-8+) phenotypes. We suggest that T3+4-6-8- cells are a productive, transitional stage in T-lymphocyte development. PMID- 3092223 TI - Negative trans-regulation of T-cell antigen receptor/T3 complex mRNA expression in murine T-lymphoma somatic cell hybrids. AB - The antigen-specific T-cell receptor (TCR) is composed of variable antigen recognition chains TCR-alpha and TCR-beta in noncovalent association with the invariant T3 multimer. The TCR-alpha and TCR-beta chains are encoded by gene segments that must be juxtaposed by rearrangement in order to be expressed. To examine whether mechanisms other than gene rearrangement might regulate TCR/T3 gene expression, somatic cell hybrids were formed among closely related murine SL12 T-lymphoma clones that differ in TCR/T3 mRNA levels. In hybrid cells formed between cell clones in which one parent is TCR-beta+ and the other is TCR-beta-, the resultant hybrid cells lack detectable TCR-beta transcripts. Since the protein synthesis inhibitor cycloheximide partially reverses TCR-beta repression in the hybrid cells, we postulate that a labile repressor protein is involved. The amount of mRNA encoding one of the T3 polypeptide chains, T3-delta, is also strongly negatively transregulated in the same hybrid cells in which TCR-beta mRNA expression is repressed. The negative trans-regulation of TCR-beta and T3 delta mRNA expression is relatively specific, since the levels of TCR-alpha mRNA and several thymocyte surface antigens are not repressed in somatic cell hybrids. Our results indicate that rearrangement of the TCR genes alone is not sufficient for TCR-beta expression and that trans-acting factors regulate the amounts of both TCR-beta and T3-delta mRNA in this system. PMID- 3092224 TI - Expression of T3 in association with a molecule distinct from the T-cell antigen receptor heterodimer. AB - The T-cell antigen receptor consists of a disulfide-linked heterodimer (Ti) that is associated with another set of three nonpolymorphic, noncovalently linked peptides termed "T3." The cell surface expression of T3 has been thought to depend upon association with Ti. In this study, we demonstrate that T3 can be expressed in the absence of an associated Ti molecule on a T-cell leukemic line, PEER. Instead, on this cell line, T3 appears to be expressed in association with a 55- to 60-kDa glycoprotein that has a peptide backbone of 29 kDa. PEER fails to express Ti alpha-chain transcripts but does express Ti beta- and gamma-chain transcripts. Using a monoclonal antibody that reacts with nonpolymorphic epitopes expressed on Ti, WT31, we demonstrate that PEER fails to react with this antibody but does react with three independently derived anti-T3 antibodies. Moreover, a small subpopulation of T3-positive peripheral blood lymphocytes, like PEER, fails to express the antigenic determinants recognized by WT31. These results suggest that, on these normal lymphocytes, T3 may likewise be associated with a non-Ti molecule. The possibility that the 55- to 60-kDa molecule expressed on PEER, termed "Tp55-60," represents the protein product of the previously identified Ti gamma-chain gene is discussed. PMID- 3092226 TI - Why I feed patients with trauma and sepsis. PMID- 3092227 TI - When I feed medical patients. PMID- 3092228 TI - How I feed patients enterally. PMID- 3092225 TI - Abnormal response to DNA crosslinking agents of Fanconi anemia fibroblasts can be corrected by transfection with normal human DNA. AB - Primary skin fibroblast cell lines from patients with Fanconi anemia were cotransfected with UV-irradiated pSV2neo plasmids and high molecular weight DNA from normal human cells. Restoration of a normal cellular resistance to mitomycin C (MMC) was observed provided that a Fanconi anemia cell line is selected for DNA mediated transformation (neo gene) and that at least two successive rounds of transfection are performed. Cells were selected by taking advantage of the higher proliferation rate and plating efficiency of the MMC resistant transformants. As estimated from reconstruction experiments, the frequency of transfer of MMC resistance lies between 1 and 30 X 10(-7). The MMC resistance phenotype was maintained for at least 10 generations following transfection. Evidence for DNA mediated transformation also includes the recovery of a normal pattern of DNA semiconservative synthesis after treatment with 8-methoxypsoralen and 365-nm UV irradiation, and the presence of exogenous pSV2neo DNA sequences was shown by Southern blot analysis. The acquired MMC resistance is probably due to the presence of DNA from normal cells. Indeed, sensitivity to MMC was maintained when Fanconi anemia cells were cotransfected with the UV-irradiated pSV2neo plasmid mixed with their own DNA or with yeast or salmon sperm DNA. These negative results also render unlikely the selection of spontaneous MMC resistant revertants in transfection of Fanconi anemia cells with normal DNA. These experiments establish the prerequisites for the isolation of the gene(s) involved in the response to DNA crosslinking lesions in human cells. PMID- 3092229 TI - How I feed patients intravenously. PMID- 3092230 TI - Differential effects of hyperthermia on human leukocyte production of interferon alpha and interferon-gamma. AB - Hyperthermia is being used clinically in the treatment of neoplasms. However, there are insufficient data regarding effects of hyperthermia on leukocyte functions potentially important in antitumor immunity. In order to provide such data, human mononuclear leukocytes were exposed to moderate (40.7 degrees C) and marked (42.7 degrees C) hyperthermia for 2 hr. Leukocyte viability, measured by dye exclusion, was not altered by such exposures. Exposure of the cells to moderate hyperthermia did not alter leukocyte production of interferon-alpha in response to influenza virus or interferon-gamma in response to the mitogen phytohemagglutinin. Exposure of the cells to marked hyperthermia significantly depressed production of interferon-alpha. In contrast, production of interferon gamma was not altered by exposure of the leukocytes to marked hyperthermia. Many studies support a role for interferons (alpha as well as gamma) in antitumor immunity. The current and other data suggest that marked hyperthermia in cancer therapy should be applied locally whenever possible, rather than to the whole body, in order to limit adverse effects on immunity. The data suggest further that interferon-gamma may be a heat shock (stress) protein for human leukocytes. PMID- 3092232 TI - [The professional responsibility of the ward head nurse]. PMID- 3092231 TI - Comparison of verapamil and nifedipine in thrombosis models. AB - Calcium blockers and calmodulin antagonists have been reported to inhibit the aggregation of blood platelets in vitro. In the present study, the effects of two calcium blockers, verapamil and nifedipine, were compared in several rodent thrombosis models. In rat and mouse platelet-rich plasma, preincubation with either verapamil or nifedipine had a dose-dependent inhibitory effect on collagen induced aggregation (P less than 0.01). The concentration required for 50% inhibition of rat platelet aggregation was 0.91 X 10(-4) M for verapamil and 1.77 X 10(-4) M for nifedipine. In in vivo thrombosis models in mice, acute pretreatment with nifedipine had a significant, dose-dependent protective effect (P less than 0.05). At a dose of 500 micrograms/kg, nifedipine inhibited thrombotic sudden death provoked by arachidonic acid, a thromboxane agonist (U46619), or a combination of collagen and epinephrine. In vivo platelet depletion induced by U46619 was also inhibited by this calcium blocker. Thus, nifedipine is protective against a variety of thrombotic stimuli, and its antiplatelet aggregatory effect apparently extends to the in vivo situation. In contrast, no in vivo antithrombotic activity was observed for verapamil. Two additional calcium blockers, perhexilene and diltiazem, and three calmodulin antagonists, W-7, chlorpromazine, and trifluoperazine, were also tested in the U46619-induced thrombotic sudden death model. Of these, only diltiazem (5 and 10 mg/kg) had an acute protective effect. PMID- 3092233 TI - [Nursing problems in total parenteral nutrition in neonatology]. PMID- 3092234 TI - [Didactic-educational purpose and results of a screening for obesity and diabetes carried out during nursing apprenticeship]. PMID- 3092235 TI - [How to arrive at nursing leadership in Italy]. PMID- 3092236 TI - [From Zambia: experience and testimony]. PMID- 3092237 TI - Genetic and molecular genetic studies of mutation induction in an excision defective strain of Drosophila melanogaster. PMID- 3092239 TI - The present status of validation of the wing spot test in Drosophila. PMID- 3092238 TI - Modulation of mutagen-induced biological effects by inhibitors of DNA repair. PMID- 3092240 TI - Correlation of UDS proficiency and removal of specific alkylation products in repair-deficient strains of Drosophila. PMID- 3092241 TI - Genetic regulation of the cytochrome P-450 system in Drosophila melanogaster. PMID- 3092242 TI - Comparison of Drosophila melanogaster chromosome breakage assays, including an evaluation of the hyperploidy test. PMID- 3092243 TI - Positive genetic hazard predictions from short-term tests have proved false for results in mammalian spermatogonia with all environmental chemicals so far tested. AB - Eleven chemicals for which there has been considerable human exposure were chosen for study by the mouse specific-locus method because of their positive mutagenic action in other test systems. All were positive in the Drosophila sex-linked recessive lethal test, and all of the ten tested in mammalian somatic cells proved mutagenic. Positive results were also obtained in other tests. In contrast, in mouse stem-cell spermatogonia none of the chemicals, even at maximum tolerated dose, has given a specific-locus mutation frequency higher than the control, and the mutation frequency for all eleven combined (12 mutations in 298, 502 offspring) is actually less than the historical control, though not, of course, significantly lower. Absence of mutation induction cannot be attributed to: failure of the chemicals to reach the testis (10 of them are known to reach the testis in active form), small sample size (the samples are large), insensitivity of the test (the test is not insensitive: a positive control gave a mutation frequency 132 times higher than the historical control). It is concluded that mammalian stem-cell spermatogonia have an effective repair capability. This is supported by the dose-response and dose-fractionation results with ethyl nitrosourea. Therefore, positive genetic hazard predictions from short-term tests on chemicals may frequently give false warning of what to expect in mammalian spermatogonia, the cells considered to be of major concern for genetic risk in human males. PMID- 3092244 TI - Hormonal aspects of the regulation of dopa decarboxylase in Drosophila melanogaster. PMID- 3092245 TI - Extra joints and misoriented bristles on Drosophila legs. PMID- 3092246 TI - Characterization of a growth factor secreted by rat Sertoli cells in culture. PMID- 3092247 TI - Control of neural crest cell migratory pathways and directionality. PMID- 3092248 TI - Molecular and cellular differentiation of muscle, cartilage, and bone in the developing limb. PMID- 3092249 TI - Microtubule organization during polar cap mitosis and pole cell formation in the Drosophila embryo. PMID- 3092250 TI - Effects of nitroglycerin, dipyridamole, nifedipine, verapamil and diltiazem on canine coronary arterial rings contracted with 5-hydroxytryptamine and anoxia. AB - Anoxia has been shown to potentiate the constrictor effects of 5 hydroxytryptamine (5HT) in isolated vascular tissue. In the present study, canine coronary arterial rings were incubated with various treatments and exposed to 5HT (4 X 10(-7) M) and anoxia (95% N2 and 5% CO2). Developed tension was increased by 250 +/- 40 mg by 5HT alone and 2,000 +/- 90 mg by 5HT and anoxia. Calcium (5 mM) potentiated, while inorganic (lanthanum, 10(-2) M) and organic calcium antagonists (nifedipine, verapamil and diltiazem; IC50 = 7 X 10(-9), 7.3 X 10(-8) and 2.4 X 10(-7) M, respectively) blocked the anoxic potentiation. Anoxia alone decreased resting tension (RT). Methysergide 3 X 10(-5) M inhibited both the 5HT- and anoxia-potentiated responses. Nitroglycerin decreased RT and inhibited the anoxic response (IC50 = 7.6 X 10(-6) M), while dipyridamole decreased RT and did not affect the anoxic response. These data suggest that the potentiation of 5HT contraction by anoxia is dependent upon extracellular calcium influx and is linked to a 5HT receptor. In addition, inhibition of the anoxic response can be achieved at other sites and is not a property common to all coronary vasodilators. PMID- 3092251 TI - Phthalocyanines as photosensitizers in biological systems and for the photodynamic therapy of tumors. PMID- 3092252 TI - Psychophysiological profiles of the Roman strains of rats. AB - Male rats of the Roman High and Roman Low Avoidance strains were submitted to four principal behavioral tests: food-motivated acquisition of bar-pressing in Skinner box, delayed reinforced alternation, locomotor activity in a "multibox apparatus," conditioned suppression, and two biological measures: blood pressure and brain octopamine level. Performances of RLA and RHA rats were significantly different in each behavioral test. Blood pressure was higher in RHA, but the difference only approached the 0.05 threshold. As previously reported, brain octopamine levels of RHA rats were significantly higher than those of RLA. A multivariate treatment (analysis of correspondences) was applied to the data of 10 behavioral tests. The main factor extracted by this treatment clearly separated the two strains. Among the variables which best differentiate RHA and RLA rats, several do not involve stress (working memory, acquisition of bar pressing, and locomotor activity). PMID- 3092253 TI - Inhibition of gold thioglucose lesion formation in the ventromedial hypothalamus by a glucocorticoid. AB - A single intraperitoneal injection of gold thioglucose (GTG) yields a lesion in the ventromedial hypothalamus (VMH), eventually producing obesity. The anti inflammatory compounds, aspirin or glucocorticoid (GC), have been shown previously to block GTG lesion formation in the VMH when examined at the light microscopic level. Ultramicroscopic changes in the VMH have been observed to account for the inhibition of GTG-induced lesions with aspirin. We sought to determine whether or not GC action in the prevention of GTG lesion formation was also accompanied by VMH morphological changes at the ultrastructural level. Our results demonstrated that hydrocortisone pretreatment completely protected the VMH from any GTG-induced necrosis. We hypothesize that this inhibition of GTG lesion formation is not mediated by GC anti-inflammatory activity, but related to an anti-insulin activity of GC, GC-induced changes in VMH cell membrane receptor function, and/or alterations in serotonin metabolism. PMID- 3092254 TI - Modification of the antitumor action of Corynebacterium parvum by stress. AB - Social grouping and isolation of mice, in the presence of an acute stressor, were found to differentially affect the antitumor action of the immunological adjuvant Corynebacterium parvum. Socially grouped DBA/2j mice were injected intradermally with P815 mastocytoma ascites cells. Half the mice had a threshold dose of C. parvum admixed with the P815 cells. Half the mice in each of those conditions were given acute, inescapable electric footshock. In a second experiment, the stressed mice were socially isolated prior to the acute stress. Tumor growth itself was not affected by the stress procedures. C. parvum inhibited tumor growth in non-stressed and socially isolated, stressed mice. However, social grouping selectively negated the C. parvum effect resulting in tumor growth and mortality equivalent to mice not given the adjuvant. Psychological factors may be important to the development of concomitant immunity and the efficacy of immunotherapies. PMID- 3092255 TI - Central glucagon-induced hyperglycemia is mediated by combined activation of the adrenal medulla and sympathetic nerve endings. AB - Intracerebroventricular (ICV) microinjection of glucagon (0.0025-2.5 micrograms) produced significant dose-dependent hyperglycemia in mice. This hyperglycemic effect was prevented by pretreatment with the sympathetic ganglionic blocker chlorisondamine chloride or bilateral adrenalectomy plus chemical sympathectomy with 6-hydroxydopamine. Similar pretreatments had no effect on the plasma glucose responses to systemic glucagon administration. Pretreatment with somatostatin, which blocks pancreatic glucagon secretion had no effect on the hyperglycemic response to central glucagon administration. The results suggest that the increase in plasma glucose following central glucagon administration is mediated by combined action of adrenal and sympathetic amines to stimulate hepatic glucose production, or additionally to inhibit insulin release from the pancreas. The possible involvement of glucagon in the central nervous system in systemic glucoregulation is discussed. PMID- 3092256 TI - Inhibition of lens aldose reductase by Labiatae flavonoids. PMID- 3092257 TI - [Psychosomatic aspects of protein-calorie malnutrition in early childhood in a tropical environment. Facts and hypotheses]. AB - After a brief look at the clinical descriptions of marasmus and kwashiorkor, and a summary of the physiopathological concepts of these protein calorie malnutritions (PCM), the author looks at arguments which suggest there is a change in the mother-child relationship at the onset of PCM, excluding, however, those malnutritions which appear in conditions of famine or catastrophe. These arguments are drawn principally from studies done in Africa, and are based on clinical, sociological, and ethnopsychiatric data. The contributing factor of maternal depression and that of relational characteristics of the child are considered, and an analysis is made of how these factors might converge at the onset of PCM. The author attempts to demonstrate the important role of a psychomotor retardation in the tableau of psychological troubles which present themselves during the course of Kwashiorkor. The role and importance of weaning, of the separation and the psychomotor retardation in the genesis of the "situation of malnutrition" are discussed. Finally, a parallel is established between PCM and early psychosomatic syndromes observed in the west, principally the anorexias and insomnias during the first year of life. The point in common between these situations and PCM is perhaps the onset of conditions having an upsetting and distorting effect on the mother-child relationship. The family and the entourage use certain collective representations in Africa ("Nit-KuBon", "Tjid-a-Paxer") to try and explain the onset of PCM. The description of these traditional representations is utilized as a materialization, by the mother and the social group, of an alteration of the mother-child relationship, and can be compared to representations which play the same role in the west. PMID- 3092259 TI - The merits and problems with the concept of projective identification. AB - This paper reviewed the merits of and problems with the concept of projective identification. On the negative side, lack of universal meaning of the term was cited. Personal countertransference receives little regard, while an isomorphic reading of patient feelings may be used to gratify omnipotent symbiotic analyst and patient fantasies. On the positive side, the concept offers a framework that can lead to deeper understanding of difficult therapeutic situations. It helps the analyst process and contain distressing feelings and eschews interpretation that can be destructive to the analytic process. Proper use of projective identification should engage the patient's ego rather than foster passivity and merger wishes. Case material was presented which illustrated problems with and merits of the concept. Personal countertransference, especially therapeutic omnipotence, was shown to receive insufficient attention. The important role of complementarity in projective identification was illustrated in the treatment of depression, a disorder which can offer difficult treatment resistances. In conclusion, the concept should not be used as a justification for analyst omnipotence and avoidance of countertransference responsibility. The concept, however, can lead to a deepening of the analytic situation if it is used with caution and respect for the patient's separateness. PMID- 3092258 TI - Cytochalasin B changes the cytoskeletal organization in Newcastle disease virus infected cells. AB - The microfilament structures of Newcastle disease virus (NDV)-infected BHK-21 cells were studied in the presence (5 micrograms/ml) or absence of cytochalasin B (CB) by means of phase contrast, indirect immunofluorescence and thin-section immunoelectron microscopy. The results indicated that CB treatment not only impaired virus infections titers and antiactin fluorescence strength but also disrupted cytoplasmic membrane and untagged ferritin-conjugated antibody on the surface of NDV specific antigens. PMID- 3092260 TI - Some comments on cerebral hemispheric models of consciousness. PMID- 3092261 TI - On death and immortality: reflections on Malinowski's fieldwork. PMID- 3092262 TI - On men and friendship. PMID- 3092263 TI - The Dream of the Rood: a few psychoanalytic reflections. PMID- 3092264 TI - Equus: the ritual sacrifice of the male child. PMID- 3092265 TI - Improper "Bostonians". PMID- 3092266 TI - Central and peripheral effects of 6-hydroxydopamine on exercise performance in rats. AB - 6-Hydroxydopamine (6-OHDA) injected into the lateral cerebral ventricles of rats impaired their exercise performance until exhaustion (treadmill run and swimming). The injected rats displayed significantly less training-induced improvement of swimming performance than did the control animals. Reduced performance also was seen in adult rats treated intraperitoneally with 6-OHDA in the neonatal or adult periods. The functional impairment can be explained by the neurotoxic action of 6-OHDA on monoamine brain structures (substantia nigra and locus ceruleus) and/or on peripheral sympathetic innervation, the latter assessed by histofluorescence of the iris muscle. The possible contribution of lacticacidemia to the reduced tolerance to stress of 6-OHDA-treated rats by the intracerebroventricular route also is considered. PMID- 3092267 TI - Associations among dexamethasone non-suppression and TRH-induced hormonal responses: increased specificity for melancholia? AB - TRH-induced thyrotropin (TSH), prolactin (PRL), and growth hormone (GH) responses were investigated together with a dexamethasone suppression test in female psychiatric inpatients with major melancholic depression (n = 21), schizophrenic disorder (n = 20), alcohol dependence (n = 11), and adjustment disorder with predominantly depressed mood (n = 13), as well as in 15 healthy women. Abnormal responses for all four endocrine variables were noted most frequently in melancholia; however, a significant number of the non-depressed patients also had abnormal hormonal responses in the individual test. The association of two or three abnormalities proved to be quite specific for the melancholic group. There were no statistically significant differences in TRH-induced TSH responses among the patient subgroups. Non-suppression of cortisol after dexamethasone was associated with blunted TSH-responses only in melancholia. There was a tendency for non-suppressor schizophrenics to show more abnormal GH-responses to TRH administration. PMID- 3092268 TI - The prolactin response to thyrotropin-releasing hormone in depressed patients and normal subjects. AB - The prolactin (PRL) response to thyrotropin-releasing hormone (TRH) was studied in depressed patients (while ill or during remission) and in normal volunteers. Depressed women were shown to have lower basal PRL and lower PRL after TRH, but similar proportional PRL responses, compared to normal women. Depressed women also had basal thyroxine levels that were higher than those of the control women. No significant changes in PRL were noted in depressed men; in fact, there was almost complete overlap of all PRL variables between depressed and normal male subjects. Examination of the responses of PRL and of thyrotropin (TSH) to TRH revealed a significant positive relationship between the two in depressed women, but no association in men. PMID- 3092269 TI - The effects of the benzodiazepine antagonist Ro 15-1788 on psychophysiological performance and subjective measures in normal subjects. AB - Ro 15-1788 is an imidazodiazepine which was initially described as a pure benzodiazepine antagonist lacking in intrinsic actions. Although recent animal work has shown the drug to have differing intrinsic actions depending on the dose, the majority of studies on human subjects conclude that it is a pure antagonist of benzodiazepines. Two oral doses of Ro 15-1788 (30 mg and 100 mg) were compared with 5 mg diazepam and placebo in their intrinsic effects on a range of psychophysiological, performance and subjective measures in 12 healthy adult subjects. At both these doses Ro 15-1788 showed a mixture of agonist (benzodiazepine-like) effects and other non-benzodiazepine-like effects on the variables measured. Although there was no clear-cut dose-response relationship, the results suggested a predominance of benzodiazepine-like effects at the higher dose on physiological measures whilst the lower dose was observed to have greater effects on a number of behavioural and subjective dimensions. The subjective changes were the opposite of those normally found for benzodiazepines. PMID- 3092270 TI - The effect of experimentally-induced renal failure on accumulation of bupropion and its major basic metabolites in plasma and brain of guinea pigs. AB - Dosage regimen adjustments because of poor renal function are often assumed to be unnecessary for extensively metabolized antidepressants. This assumption is being increasingly questioned in recognition of the role of active drug metabolites. The purpose of this study was to assess the steady-state accumulation of the new antidepressant bupropion and its three major basic metabolites in guinea pigs, with and without experimentally-induced renal failure. Two groups of guinea pigs were treated by intraperitoneal (IP) implantation of mini-osmotic pumps containing bupropion hydrochloride. Immediately after surgery, one group of animals received an injection of uranyl nitrate. After 4 days, all animals were sacrificed by decapitation following blood removal by cardiac puncture. Analysis of plasma and brain samples by high performance liquid chromatography (HPLC) for concentrations of bupropion (BUP) and its major basic metabolites, the erythro amino alcohol (EB), the threo-amino alcohol (TB) and the hydroxy metabolite (HB) revealed greater accumulation of BUP, TB, and HB in plasma and brain of the animals with renal failure compared to controls. No difference was found between groups in the concentrations of the EB metabolite. As the guinea pig shows a BUP and metabolite plasma concentration profile similar to that seen in human studies, these results suggest that further studies of bupropion and its major metabolites are warranted in patients with impaired renal function to assess possible excessive drug and metabolite accumulation. PMID- 3092271 TI - Effects of D-Met2, Pro5-enkephalinamide on pain tolerance and some cognitive functions in man. AB - The effects of D-Met2, Pro5-enkephalinamide (EA) on pain tolerance and some cognitive functions have been examined in healthy male volunteers. Dihydrocodeine (DC) was used as reference substance. Applying the submaximum effort tourniquet technique EA (10 mg SC) was found to elevate the pain threshold similarly to DC (20 mg SC). Neither DC nor EA impaired the performance in the symbol cancellation test, which quantitates the intensity of attention. In this assay rather a slight improvement was detected. in addition the short-term memory performance (Wechsler test) was also improved by EA and DC. No alteration was seen in the word fluency test, an indicator of long-term (semantic) memory. The data show that EA not only improves pain tolerance but some of its mental effects are similar to those of a classical morphine congener DC. PMID- 3092272 TI - Contrasting baseline-dependent effects of amphetamine, chlorpromazine and scopolamine on response switching in the pigeon. AB - Both amphetamine and scopolamine increase low rates and reduce high rates of responding. It has been suggested that the dependence of the effects of these drugs on control rate may be due to their non-specific disruptive cue properties rather than to specific pharmacological actions. To examine whether this possible non-specific disruption also applied to response-choice, pigeons were trained under a schedule in which 30 key-peck responses were required. This fixed-ratio could be completed by responding in any order on either or both of two keys, and then the first switch between the two keys was reinforced by the presentation of food. Under control conditions, the probability of the birds switching between the keys increased as the ratio progressed, resulting in performance which could be analysed in a manner analogous to rate-dependent analyses of responding under fixed-interval (FI) schedules. The birds were then treated with amphetamine (0.4 3.2 mg/kg), chlorpromazine (1.0-30 mg/kg) and scopolamine (0.01-0.10 mg/kg). Amphetamine increased switching at all baselines, to probabilities greater than chance (i.e. P. switch greater than 0.5). Scopolamine resulted in response choice converging towards chance, whereas chlorpromazine reduced switching when the baseline probabilities were high. Thus: amphetamine increases switching in pigeons as it has previously been shown to do in rats, and this effect is not due to regression towards random choice, the opposite effect of a reduction in switching can occur after chlorpromazine treatment, and whereas the effects of amphetamine and scopolamine on response rate may be similar, the effects of the two drugs on response choice are dissociable, with only scopolamine resulting in a randomisation of performance. PMID- 3092273 TI - The interactive effects of alcohol and mood on dual-task performance. AB - The interactive effects of mood induction and alcohol consumption were examined in a combined visual digit detection and tracking task. Although tracking ability was independently sensitive to both time on task and alcohol, no interaction between alcohol and mood was observed. However, correct reaction times on the digit detection task were sensitive to such interactive effects. Those individuals who both consumed alcohol and watched a descriptive film performed worse on this part of the task throughout the session compared to those who watched a humorous film and did not take alcohol. Correlational analyses between performance on the tracking and digit detection tasks do not necessarily support the contention that alcohol may serve to disrupt the operation of a timesharing process. PMID- 3092274 TI - Stress-induced opioid analgesia and activity in mice: inhibitory influences of exposure to magnetic fields. AB - An exposure for 30 min to a 0.5 Hz rotating magnetic field (1.5-90 G) significantly reduced immobilization stress-induced, opioid analgesia and hyperactivity in CF-1 and C-57 BL strains of mice, respectively. The magnetic exposure also eliminated the day-night rhythm in stress-induced analgesia, with maximum inhibitory effects occurring in the dark period. Pre-treatment with naloxone (1.0 mg/kg) had comparable inhibitory effects on immobilization-induced analgesia and activity. These results suggest that exposure to magnetic stimuli can significantly influence stress-induced activation of endogenous opioid systems and their behavioral and physiological consequences. PMID- 3092276 TI - Reduced Bmax of [3H]-imipramine binding to platelets of depressed patients free of previous medication with 5HT uptake inhibitors. AB - The high-affinity binding sites for [3H]-imipramine (IMI) present in human platelets are associated with the neuronal uptake system for 5HT. It was recently demonstrated that previous antidepressant therapy with drugs which inhibit 5HT uptake could down-regulate [3H]-IMI binding and that this effect could persist up to 1 month after the end of treatment. We therefore re-examined the reported differences in Bmax of [3H]-IMI binding in platelets between control and depressed untreated patients, to evaluate the residual influence of previous antidepressant medication. The saturation characteristics of [3H]-IMI binding were compared in platelets from 17 depressed patients carefully selected according to previous antidepressant therapy and washout period, who were closely matched, for age and sex, with a group of control healthy volunteers. The results reveal a significant decrease by 47% in the Bmax of [3H]-IMI binding in platelets of untreated depressed patients when compared with controls. There was no significant modification of Kd values for platelet [3H]-IMI binding between the depressed and the control groups. Our results support the view that platelet [3H] IMI binding is a useful tool as a biological marker in depression. PMID- 3092275 TI - Enhanced selective 5-HT depletions in the DHT rat model: denervation supersensitivity and recovery of function. AB - The effects of enhancing 5-HT depletion with multiple intracisternal injections of 5,7-dihydroxytryptamine (DHT) on spontaneous or L-5-hydroxytryptophan (5-HTP) induced behaviors (videotaped) and locomotor activity (photocell recording) were studied in the adult rat. After four DHT injections, 5-HT content in septum/accumbens, hippocampus, striatum, neocortex, cerebellum, and cervical spinal cord fell to 0-10% of controls. Multiple injections also significantly improved depletions in brainstem and diencephalon, which were not as extensive. Spontaneous locomotor activity (LMA) was increased in DHT-lesioned rats for 1 week. The associated behavioral abnormalities, hindlimb hyperextension and incomplete rearing were also transient and differed from the motor syndrome evoked by 5-HTP. Multiple DHT injections did not qualitatively modify the 5-HTP syndrome but shifted the dose response curve to the left compared to single injections. Syndrome behaviors shared a similar dose threshold and could be evoked with 30 mg/kg 5-HTP. Two weeks after DHT, the locomotor response to 5-HTP (65 mg/kg) was method dependent or biphasic: decreased in brief recordings when syndrome abnormalities were greatest and increased in hour-long recordings. LMA correlated with rearing in controls and inversely with total behavioral abnormality in DHT-lesioned rats injected with 5-HTP. Multiple regression of LMA with regional 5-HT content was significant for hippocampus, striatum, and septum/accumbens. These data suggest that the development of denervation supersensitivity, the proposed mechanism of the 5-HTP-evoked motor syndrome, may be responsible for the rapid recovery of function in LMA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092277 TI - Lithium treatment of mania in a patient with recurrent ventricular tachycardia. PMID- 3092278 TI - A comparative study of the relative influence of different anticonvulsant drugs, UV exposure and diet on vitamin D and calcium metabolism in out-patients with epilepsy. AB - The biochemical parameters associated with vitamin D metabolism, calcium, 25 hydroxy-vitamin D (25OHD) and alkaline phosphatase levels were assessed in 226 out-patients with epilepsy. Patients were grouped depending on the drug treatment; carbamazepine, phenytoin, phenobarbitone and sodium valproate used alone as monotherapy and a combination of these drugs as polytherapy. The most severe alterations occurred in the polytherapy group. Hypocalcaemia was more severe in the phenobarbitone monotherapy group than the carbamazepine or the phenytoin groups. No patient on sodium valproate monotherapy had subnormal levels of calcium (less than 2.1 mmol/l). 25OHD levels were similarly reduced in the carbamazepine, phenytoin and the phenobarbitone groups with no reduction in the sodium valproate group. Significant elevations in alkaline phosphatase levels were evident in all patient groups except the sodium valproate group. This study confirms biochemical evidence for anticonvulsant osteomalacia when the enzyme inducing drugs are used, the degree of severity depending on the drug regimen. PMID- 3092279 TI - [Antibacterial concentration in the blood, teeth and jaw tissues after peri operative administration of propicillin]. PMID- 3092280 TI - [Lethal and mutagenic effect of fast neutrons of different energies on the spores of Streptomyces griseus]. AB - A study was made of lethal and mutagenic effects of fast neutrons of different energy on spores of prototrophic and auxotrophic strains of Streptomyces griseus. Relative biological effectiveness of fast neutrons is higher than that of gamma rays and depends on beam energy. Neutrons of 22-50 MeV induce Streptomyces griseus mutations more frequently (by one order of magnitude) than neutrons of 1.4-1.6 MeV do. The obtained mutants can be used in studying Streptomyces griseus genetics. PMID- 3092281 TI - Carbon fibre faced cassettes in neonatal radiography: their use and cost effectiveness. PMID- 3092282 TI - Recent developments in scrapie and Creutzfeldt-Jakob disease. PMID- 3092283 TI - Ethanol metabolizing system in Drosophila. Aldehyde dehydrogenase: functional aspects in adult and during development. AB - Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities were determined in adult flies from several Drosophila species endowed with widely different tolerance to ethanol (ETOH). Plotting ALDH against ADH activities resulted in a high correlation coefficient (r = 0.966). This finding was confirmed in developmental studies. From early larval stage up to late adult life, DH and ALDH activities demonstrated almost parallel profiles. In the highly ETOH tolerant species D. melanogaster (D.m.), ADH and ALDH profiles were U shaped: high activities in larvae, low activities in pupae and high activities in adults. In D. simulans (D.s.), a species less tolerant to ETOH, the profiles were L-shaped: high activities in larvae but low activities in both pupae and adults. Interestingly, similar activities (ADH and ALDH) were observed in the larvae of both species. Subcellular distribution studies of larval ALDH in both species revealed that the total ALDH activity is largely contributed by a mitochondrial high affinity enzyme. ALDH activity, clearly distinguishable from aldehyde oxidase (ALDOX), was visualized through analytical isoelectric focusing of the subcellular fractions. The estimated pIs for D.m. and D.s. were 4.9 and 5.2 respectively, thus different from those of ADH. The key biological role initially attributed to Drosophila ALDH is further supported by the present data. In addition the Drosophila developmental model opens new avenues for research on the study of genetic regulation of ADH and ALDH expression. PMID- 3092284 TI - Is there a future for hospital-based intensive care nursing courses? PMID- 3092286 TI - [Equipments and instruments for use in radiological protection (VI). Characteristics and use of surface and whole body monitors]. PMID- 3092285 TI - [Current diagnosis and treatment of hypogonadotropic hypogonadism in men]. PMID- 3092287 TI - [Prevalence of the penicillinase-producer Neisseria gonorrhea in a high-risk clinic, in the metropolitan area]. PMID- 3092289 TI - [Sleep and respiration. Influence of arousal status on respiration]. PMID- 3092288 TI - Dopamine control of aldosterone secretion in end-stage renal failure. AB - The role of the tonic inhibitory effect of dopamine on aldosterone secretion has been investigated in 10 patients with chronic renal failure (CRF) on hemodialysis, in 8 normotensive renal transplant recipients (Tx) with normal renal function and in 8 normotensive volunteers (NV). The following tests were performed: the response of plasma aldosterone (PA) to metoclopramide administration; the response of plasma prolactin (PRL) to TRH administration, and the changes induced by Lisuride (a dopaminergic agonist, on the values of PA and PRL). The basal values of PA and PRL were higher in CRF than in NV and Tx. The inverse was true for plasma renin activity (PRA) values. The response of PA and PRL to metoclopramide showed blunted increases in CRF when compared to NV, in the absence of changes of PRA, cortisol and potassium. After TRH administration, PRL increase in CRF was also inferior. Lisuride induced a decrease of both PA and PRL both in CRF and NV. In Tx, basal values of PA and PRL were similar to NV. Nevertheless, the response to metoclopramide and TRH were partially blunted when compared to that of NV. These results point to the existence of a deranged dopaminergic regulation of aldosterone secretion in end-stage renal failure patients. The alterations are partially corrected by a well-functioning kidney graft. PMID- 3092290 TI - Effect of gentamicin on urinary acidification in the rat. AB - The effect of gentamicin, an aminoglycoside antibiotic, on renal function and especially on acid excretion was studied in normal and acidotic rats. The doses used were 1 (G4) and 10 (G40) times the suggested human therapeutic dose on a weight basis. After 10 days of each treatment, the glomerular filtration rate (GFR) was unchanged in G4 but fell significantly (p less than 0.05) in G40. In the acidotic groups (AG4 and AG40) there was an accentuated reduction in GFR, renal plasma flow and urine/plasma insulin ratio. Normal rats showed a normal acid excretion even with the high-dose treatment but, in the acidotic group, there was a significant decrease in ammonia excretion. The amount of bicarbonate excretion was significantly elevated in those groups, leading to a greater urinary pH. These results indicate that acute metabolic acidosis enhanced the nephrotoxic effects of gentamicin and impaired the excretion of an acid overload. PMID- 3092291 TI - Phosphatase affects microsomal monooxygenase mainly via reductase. AB - Treatment with alkaline phosphatase of hepatic microsomes prepared from rabbit, rat, and mouse caused a marked decrease of their specific monooxygenase activity (7-ethoxycoumarin-deethylation). This decrease occurred without a significant change in the microsomal content of cytochrome P-450, but with an equally marked decrease of NADPH-cytochrome P-450 reductase (cytochrome c reduction). Thus the phosphatase effect on monooxygenase is mainly due to the inactivation of the reductase. PMID- 3092292 TI - Breathing pattern and neuromuscular drive during CO2 rebreathing in normal man and in patients with COPD. AB - In 11 normal subjects and in 10 patients with chronic obstructive pulmonary disease we evaluated breathing pattern and mouth occlusion pressure (PO.1), while breathing room air and during reinhalation of a hypercapnic hyperoxic gas mixture. In the breathing pattern we analyzed the time and volume components of the respiratory cycle: tidal volume (VT), inspiratory time (Ti), expiratory time (Te), total time of respiratory cycle (Ttot); mean inspiratory flow (VT/Ti) and Ti/Ttot ratios, respiratory frequency (RF) and instantaneous ventilation (VE). In the normal subjects, increase in VE during rebreathing mainly depended on an increase in both VT and VT/Ti without significant changes in Ti. During CO2 rebreathing the patients exhibited a lesser increase in VE compared to normals, due to a lesser increase in VT. However, expressing VT in percent of resting inspiratory capacity showed that VT attained at the end of rebreathing (VTmax) was similar to that noted in the normal subjects at the same minute of rebreathing. Furthermore, percent increase in VE, VT, VT/Ti and PO.1 between resting value and that at 56 mm Hg (delta %), were significant in both groups with a major increase in the normal subjects for VE and VT/Ti. In comparison, delta % decreases in both Te and Ttot were found to be significant only in the normal subjects. VT/Ti was related to VE in a similar way in the two groups. In contrast, in the normal subjects, Ti/Ttot did not increase with increasing VE. During rebreathing increase in PO.1 was found to be similar in the normal subjects and in patients. However, for a given neuromuscular drive VE and VT/Ti were greater in the normal subjects than in the patients. These data show that in the patients as a whole no significant changes in breath intervals occur during CO2 rebreathing. Furthermore, in patients, in spite of a similar increase in neuromuscular drive, the efficiency by which inspiratory muscle output (PO.1) is converted into VT/Ti was found to be reduced. PMID- 3092293 TI - Molecular reorganization during nuclear differentiation in ciliates. PMID- 3092294 TI - [Efficacy of high frequency oscillatory ventilation on Va/Q distribution in the lung with unilateral large airway obstruction]. PMID- 3092295 TI - Carotid body hypercapnia does not elicit ventilatory acclimatization in goats. AB - The carotid body (CB) perfusion model utilizes surgical vascular ligations to allow isolated blood supply to a single in situ CB in awake goats. The contralateral CB was excised. By use of an extracorporeal pump-oxygenator system the blood gas composition perfusing the CB can be controlled independently from that of the systemic arterial system including the brain. Using this model we compared the responses of systemically normoxic goats to CB hypercapnia and CB hypoxia. In 6 goats CB stimulation with hypercapnic-normoxic blood (mean PcbCO2 = 78 Torr, mean PcbO2 congruent to 100 Torr) produced acute hyperventilation (mean decrease in PaCO2 of 5.2 Torr, P less than 0.05) which remained constant over the 4-h perfusion period. Lack of a progressively increasing hyperventilation indicates that ventilatory acclimatization did not occur with hypercapnic CB perfusion. Hypoxic-normocapnic CB stimulation (mean PcbO2 = 40 Torr, mean PcbCO2 = 39 Torr) produced an acute mean decrease in PaCO2 of 5.5 Torr (P less than 0.05) in 6 additional goats. In contrast to CB hypercapnia, the acute hyperventilation induced by CB hypoxia was followed by a progressive time dependent additional mean decrease in PaCO2 of 5.6 Torr (P less than 0.05) over a 4-h period (ventilatory acclimatization). These data are compatible with the concept of separate receptor mechanisms for hypercapnia and hypoxia in the CB and suggest that the early phase of ventilatory acclimatization to hypoxia in goats may result from a time-dependent increase in CB afferent output. PMID- 3092296 TI - Diaphragm length and breathing pattern changes during hypoxia and hypercapnia. AB - In this study diaphragmatic length changes were measured during quiet breathing and during augmentation of breathing with hypoxia and hypercapnia in supine anesthetized dogs. The breathing pattern and the VT-TI relationship during hypoxia were different than those during hypercapnia. The crural diaphragm shortened more than the costal diaphragm with both stimuli, and the amount of shortening in relation to the tidal volume implied that there was considerable distortion of the chest wall during hyperventilation. The velocity of shortening of both parts of the diaphragm at similar levels of ventilation was greater during hypoxia than hypercapnia. The velocities found with hyperventilation suggested that force-velocity considerations did not reduce force generation. Hypoxic stimulation resulted in a reduction in the resting length of both parts of the diaphragm, and was associated with a positive shift in baseline pleural pressure which implied gas trapping. The large tidal diaphragmatic shortening found with augmented breathing and the shorter resting length with hypoxia indicated that length-force properties are important in force generation. PMID- 3092298 TI - Percutaneous renal surgery. PMID- 3092297 TI - Regulation of cutaneous gas exchange by environmental O2 and CO2 in the frog. AB - The effects of environmental PO2 and PCO2 on cutaneous blood flow and gas exchange were investigated in the frog, Rana pipiens. Halothane (Ha) anesthetized frogs were equilibrated with 9.5% Freon-22 (Fr), 1.1% Ha and air while placed in a box. A gas mixture, initially free of Ha and Fr, was drawn through a small test chamber placed on the abdomen. The excretion of Fr, Ha and CO2 into the sample chamber was analyzed by a mass spectrometer. Under these conditions, changes in Fr or Ha excretion into the sample chamber reflected local changes in skin perfusion. Raising sample chamber [O2] produced concentration-dependent increases in the excretion of all gases measured. Lowering chamber [O2] reduced gas excretion. Increasing chamber [CO2] to 5% decreased the excretion of Fr and Ha. Increasing box [O2] to 86.5% while keeping sample chamber [O2] constant at 21% decreased gas excretion into the chamber. Selectively raising box [CO2] to 4.3% increased gas excretion into the chamber. The results indicate that regional cutaneous blood flow and gas exchange is a direct function of the [O2] directly above that portion of skin, and inversely related to the [O2] over adjacent skin. This regional perfusion-O2 matching may act to optimize total cutaneous gas exchange in the frog. In addition, CO2 may be an important regulator of cutaneous blood flow distribution. PMID- 3092299 TI - [Virus hepatitis]. PMID- 3092300 TI - Use of bacterial vaccines for prevention of pneumococcal and meningococcal disease in the day care setting. AB - The pneumococcus causes severe disease, including meningitis and bacteremia, in children of day care age. It is also a frequent cause of otitis media. Unfortunately, the currently available pneumococcal polysaccharide vaccine has not been efficacious in children under 24 months old; research is currently underway on methods for increasing immunogenicity in young children. The meningococcus is a rare cause of meningitis in day care aged children, but children in day care are likely to be at increased risk of secondary disease if a case occurs in a center. The currently available polysaccharide meningococcal vaccine is poorly immunogenic in children younger than two and does not include the group B polysaccharide, which is responsible for 70% of disease in children younger than five years. Therefore, chemoprophylaxis with rifampin is recommended for decreasing the risk of secondary spread. When a group B meningococcal vaccine immunogenic in young children becomes available, vaccination will be indicated for all children in day care. PMID- 3092301 TI - Penicillin-binding proteins and the antibacterial effectiveness of beta-lactam antibiotics. AB - It is currently believed that both the antibacterial potency and the nature of the antibacterial effects of beta-lactam antibiotics are ultimately dependent on the inhibition (acylation) of one or more of the bacterial penicillin-binding proteins (PBPs). Nevertheless, bacterial factors (e.g., autolysins) that do not directly react with the antibiotic molecule also profoundly influence the fate (inhibition of growth or lysis) of the antibiotic-treated bacterial cell. The quantitative relationship between the minimal inhibitory concentration of a beta lactam antibiotic and its reactivity with certain PBPs is not well understood. Also poorly understood is the mechanism by which inhibition of PBP function causes triggering of suicidal autolytic activity. Much remains to be done before the structural basis of the highly selective PBP affinities observed with some beta-lactam antibiotics is understood. A new form of antibiotic resistance involving mutational alteration of PBPs (in the direction of lower antibiotic affinity) has emerged among clinical isolates of most of the major human pathogens. PMID- 3092302 TI - Properties and characteristics of a new immunoglobulin G intravenous preparation. A symposium. Chicago, Illinois, June 7, 1985. PMID- 3092303 TI - Three generations of immunoglobulin G preparations for clinical use. AB - The first purified human immunoglobulin G (IgG) preparation used clinically was immune serum globulin (ISG), which was prepared in the 1940s by E. J. Cohn's group. It was originally formulated in water with 0.3 M glycine at pH 6.8 and was 70%-80% monomeric. ISG was safe when given intramuscularly and efficacious for measles and hepatitis prophylaxis. The next generation of purified IgG began in the 1960s with chemically modified preparations suitable for intravenous administration. The first such IgG intravenous preparation (IGIV) in the United States was IGIV pH 6.8 (Gamimune, Cutter Biological), in which the anticomplement activity found in ISG was removed by reduction and alkylation of disulfide bridges. This product was originally formulated as a 5% IgG solution in water (pH 6.8) with 0.2 M glycine in 10% maltose for stabilization. It remained stable for at least 2.5 years at 5 degrees C, was 80%-90% monomeric, had virtually no anticomplement activity, was safe given intravenously, and was efficacious for prophylaxis in agammaglobulinemic patients. A third generation of purified IgG has since been developed; IGIV pH 4.25, (Gamimune N, Cutter Biological), which was isolated by the Cohn method from human plasma and is safe for intravenous use, is a 5% solution of IgG in water (pH 4.25) with 10% maltose. The product is greater than 99% IgG, greater than 95% monomeric, and has greater than 90% less anticomplement activity than ISG. PMID- 3092304 TI - Comparative studies of impurities in intravenous immunoglobulin preparations. AB - In a comparative study, seven commercially available immunoglobulin preparations and one experimental preparation, processed by various manufacturers in the United States and Europe, were investigated for non-IgG proteins and impurities. The basic fractionation methodology affects the purity of subsequently processed intravenous preparations. Five of the seven products manufactured in Europe contained varying amounts of plasma proteins other than IgG. A residual heterologous protein was detected and quantitated in one product whose processing includes porcine pepsin treatment. Only one of the eight products was low in aggregates (as judged by both anticomplement activity and nephelometric turbidity), while three products contained anticomplement activity at levels high enough to be a potential cause of reactions in patients. In general, the level of prekallikrein activator activity was proportional to that of amidolytic activity; four products had only trace levels of amidolytic activity as well as prekallikrein activator. Only one product contained significant isoagglutinin levels, while six products had detectable IgA levels. PMID- 3092305 TI - IgG subclass composition of intravenous immunoglobulin preparations: clinical relevance. AB - Each immunoglobulin G (IgG) subclass has unique physicochemical properties and, probably, unique functions. Each heavy chain is coded by a separate gene on chromosome 14. Deficient synthesis of a subclass may be associated with recurrent or chronic infections, the deficiency not being detected by measurements of levels of total serum IgG. Measurement of levels of IgG subclasses should be part of the work-up of patients who have frequent infections but have normal levels of major immunoglobulin classes. Deficiencies of IgA or IgE frequently coexist with deficiencies of IgG2 or IgG4. Patients with a subclass deficiency often benefit from replacement therapy with intramuscular or intravenous IgG or plasma from a donor free of hepatitis and HTLV-III viruses. It may be critical to provide IgG or plasma that is a good source of the missing immunoglobulin class or subclass. Sometimes it is necessary to administer a product with antibodies to the virus or bacteria responsible for a particular infection. PMID- 3092306 TI - Protective and opsonic activities of a native, pH 4.25 intravenous immunoglobulin G preparation against common bacterial pathogens. AB - The in vitro opsonic activity of a native, pH 4.25 immunoglobulin G preparation modified for intravenous use (IGIV pH 4.25) was compared with the activities of a standard reduced and alkylated, pH 6.8 preparation (IGIV-R/A pH 6.8) and a reduced and alkylated, pH 5.25 preparation (IGIV-R/A pH 5.25) against a variety of common bacterial pathogens. In most instances the opsonic titers of IGIV pH 4.25 equaled or exceeded that of IGIV-R/A pH 6.8; IGIV-R/A pH 5.25 usually had an intermediate level of activity. The protective activity of IGIV pH 4.25 against Escherichia coli in a neonatal rat model was also greater than that of IGIV-R/A pH 6.8. Thus, the functional activity of the new IGIV pH 4.25 apparently equals or exceeds that of standard reduced and alkylated preparations. PMID- 3092307 TI - Effect of intravenous immunoglobulin G on neutrophil kinetics during experimental group B streptococcal infection in neonatal rats. AB - A modified form of serum immunoglobulin G (pH 4.25) was tested for its effect on neutrophil kinetics and survival rates in neonatal rats with type III, group B streptococcal pneumonia and sepsis. Each of 30 animals received a transthoracic inoculation of 10(5) organisms/g of body weight; all died within 48 hr. When 100, 1,000, or 2,000 mg of immunoglobulin G/kg was administered intraperitoneally at the time of bacterial inoculation, survival rates rose to 20%, 90%, and 100%, respectively. Even when the immunoglobulin preparation was administered intraperitoneally 2 hr after transthoracic inoculation of bacteria, all 19 animals survived. Only seven of 15 animals survived when immunoglobulin administration was delayed for 22 hr. Immunoglobulin facilitated the neutrophil inflammatory response: when immunoglobulin (rather than an albumin control) was administered, neutrophils were released more rapidly from the storage pool and accumulated more quickly at the site of bacterial inoculation. Unlike infected control animals, immunoglobulin recipients did not develop neutropenia or depletion of the neutrophil storage pool. PMID- 3092308 TI - Use of a new, low-pH immunoglobulin G preparation during episodes of bacteremia in the rat. AB - A rapidly expanding role for immunoglobulin G preparations in conditions other than the classical immunodeficiency syndromes is evident. This relatively new concept of treatment with polyclonal antibody has been tested in the rat with severe Salmonella typhimurium bacteremia with use of a newly developed, native immunoglobulin G preparation for intravenous use (IGIV pH 4.25). IGIV pH 4.25 increased survival time and decreased absolute mortality, prevented hypotension and acidosis, and ameliorated or prevented changes in variables indicative of organ damage during S. typhimurium bacteremia in the rat. Intravenous infusion of IGIV pH 4.25 at high rates did not cause further deterioration in the arterial blood pH in the acid-base-compromised rat and hence should not cause clinically significant decreases in pH in patients with compromised acid-base regulating systems. PMID- 3092309 TI - Immunoglobulin G: potentiation of tobramycin and azlocillin in the treatment of Pseudomonas aeruginosa sepsis in neutropenic mice and neutralization of exotoxin A in vivo. AB - Mice with cyclophosphamide-induced neutropenia were challenged with four immunotypes of Pseudomonas aeruginosa by contamination of a small dorsal surface wound. The infections were lethal; 100% of control animals (n = 80) treated only with albumin died. Administration of an immunoglobulin G intravenous preparation (IGIV) and/or therapy with tobramycin or azlocillin was begun 16 hr after challenge. Mortality among mice (n = 120) treated only with an antibiotic was 75.0%, while that among mice (n = 80) treated only with IGIV was 78.8%. Combination therapy with IGIV and an antibiotic (n = 120) resulted in mortality of 38.3%. The protection afforded by IGIV may have resulted in part from neutralization of exotoxin A, as mice treated with IGIV before challenge with exotoxin A were subject to lower mortality and had lower levels of serum aspartate and alanine aminotransferases than controls. PMID- 3092310 TI - Half-life and clearance of pH 6.8 and pH 4.25 immunoglobulin G intravenous preparations in patients with primary disorders of humoral immunity. AB - The half-life (t1/2) and clearance of IgG and three antibodies--to tetanus, pneumococcus type 3, and pneumococcus type 7--were evaluated in 38 patients who participated in a multicenter, double-blind, crossover study comparing two immunoglobulin G intravenous preparations, IGIV pH 6.8 and the new IGIV pH 4.25. IgG metabolism was evaluated after the sixth infusion by measuring the decline in concentration of IgG and specific antibody. The t1/2 values of IgG varied greatly, but the mean values of 32 and 37 days are comparable to those determined in previous studies with use of radiolabeled IgG and are longer than those reported in normal volunteers. The t1/2 values for specific antibodies, especially those to tetanus, tended to be shorter than those for IgG. The clearance of IgG and antibodies also varied widely, but even though there was some relationship between the clearance and t1/2 in individual patients, the poor correlation (R2 less than .5) suggested that other factors, such as redistribution or loss of damaged molecules, are as important as the catabolic rate. Thus, clearance may be a more reliable parameter than t1/2 in evaluating the metabolism of IgG. PMID- 3092312 TI - [The hyper-IgE syndrome]. PMID- 3092311 TI - Safety and toxicity of a new serum immunoglobulin G intravenous preparation, IGIV pH 4.25. AB - A new preparation of serum immunoglobulin G for intravenous use (IGIV) was investigated. The reagent, IGIV pH 4.25, is a liquid preparation of native, unmodified human serum IgG without preservatives but stabilized in 10% maltose. Its physical characteristics have multiple advantages over those of other available IGIV preparations. In a multicenter, randomized, double-blind, crossover study, this product was compared with a commercially available standard preparation, IGIV pH 6.8. Thirty-nine patients with various forms of primary immunodeficiency disease received infusions consisting of 400 mg/kg every four weeks; an overall total of 232 infusions were administered. Extensive clinical and laboratory observations were made. Adverse effects from infusion therapy were transient and minimal. No clinically significant abnormalities in vital signs and laboratory values occurred. There were no statistically significant differences between the results for IGIV pH 6.8 and those for the new IGIV pH 4.25 preparation. It was possible to infuse the new IGIV pH 4.25 reagent rapidly (0.1 ml/kg per hr) without inducing vasomotor adverse effects. PMID- 3092313 TI - [Ultrastructural changes in the jejunal mucosa in acute and chronic enterocolitis in infants and young children]. PMID- 3092314 TI - [Diagnostic value of spinal puncture in severe infections in infants]. PMID- 3092315 TI - [Humoral defense in acute diarrhea in infants]. PMID- 3092317 TI - [Transcutaneous measurement of partial oxygen pressure]. PMID- 3092316 TI - [Case of McDuffie's hypocomplementemic leukocytoclasic vasculitis]. PMID- 3092318 TI - [Experimental study of the intravenous use of a new antibiotic combination in severe infections in neonates, infants and small children]. PMID- 3092319 TI - [Ion Nicolau--on the centenary of his birth]. PMID- 3092321 TI - [Study of the HLA-DQ system by the complement fixation test on lymphocytes stimulated by phytohemagglutinin. Existence of HLA-DQX allele(s)]. AB - The complement fixation microtechnique against PHA blasts has been used to study HLA-DQw1, 2, 3 specificities with sera from multiple transfused patients and/or from multiparous women. Several sera (6 or 7) have been used to define each DQ specificity. The sera have been chosen because of their reactivity with cells from HLA-DR 1, 2 or w6 donors (for DQw1), DR3 or 7 donors (for DQw2,) DR4 or 5 donors (for DQw3). Correlation coefficients between DQ and DR specificities were from 0.56 to 0.91. Correlation coefficients between sera were from 0.51 to 0.92 in each cluster of sera. The segregation of DQw1, 2, 3 specificities has been studied in 46 families with 234 children. This study showed haplotypes lacking DQw1, 2, 3 specificities. The segregation of such 11 DQX haplotypes has been observed in 38 children from 8 families; 5 children were DQX/DQX homozygotes. Up to now, no serological reagent defining the specificity (or specificities) corresponding to DQX has been found. No preferential association was observed between DQX and DR specificities. The gene frequencies observed in 170 haplotypes in these 46 families were as follows: DQw1: 0.400; DQw2: 0.252; DQw3: 0.282; DQX: 0.065. Detecting DQ specificities seems easier by CF on PHA blasts than by lymphocytotoxicity microtechnique against B lymphocytes and monocytes from pheripheral blood. This suggests that PHA blasts express larger quantities of DQ molecules than B lymphocytes and monocytes. The results confirm that complement fixation microtechnique against PHA blasts is efficient for HLA-DQw typing. PMID- 3092322 TI - [Treatment of pain in the emergency ward in the hospital]. PMID- 3092320 TI - [Cardiomyopathies in children (I)]. PMID- 3092323 TI - [Current developments in vaccinations]. PMID- 3092324 TI - [Where is pediatrics headed? The conjecture through 1 year of "Medico e Bambino"]. PMID- 3092325 TI - [Dossier: protocols for nursing. A theoretical and practical guide]. PMID- 3092326 TI - [Pilot study of the nursing problems of women with tumors]. PMID- 3092327 TI - [Reasons and grounds for the routes and time intervals of drug administration]. PMID- 3092328 TI - [Nursing of the terminal patient]. PMID- 3092329 TI - [Hospital infections and invasive procedures]. PMID- 3092330 TI - [Cancer pain]. PMID- 3092331 TI - [Elderly chronic patients institutionalized: the role of nurses]. PMID- 3092332 TI - Cost and effectiveness of different approaches to schistosomiasis control in Africa. AB - In order to analyze the cost-effectiveness of selected mass-chemotherapy, a model is used to compare the treatment of urinary schistosomiasis with metrifonate (3 dose regimen, fortnightly intervals) and praziquantel (one dose regimen). The model was applied to two situations. Setting I, based on experiences in the Peoples Republic of the Congo, assumes that the average distance between the project base and the area of intervention is 80 km, the other, setting II, based on the situation in Mali, assumes an average distance of 250 km. The aim of the project is defined as the reduction of a prevalence of 50% to less than 5% in the absence of reinfection. Using metrifonate, the cost per person rendered negative is calculated at DM 12.57 for the Congo and at DM 32.52 for Mali. Prevalence will be 4.2% after intervention. Using praziquantel, the costs are DM 8.36 and 11.47, respectively, and the prevalence reached at the end of the intervention will be 1.1%. The cost difference is mainly due to the high operational cost incurred by the 3 dose regimen. Once low prevalence levels are reached, operational cost further outweigh drug expenses. PMID- 3092333 TI - A proposed evaluation of a primary health care approach to control schistosomiasis in Zimbabwe. AB - Zimbabwe has undertaken a national control programme for schistosomiasis. Targets have been set for the next five year period and implementation of the programme will be through the primary health care system. Improved water supplies and sanitation are seen as a major part of the programme which will be supplemented by chemotherapy. A pilot programme is underway to provide information on various aspects of implementation and evaluation for incorporation into the national programme. Evaluation of the pilot programme and a proposed evaluation for the national programme are discussed. PMID- 3092334 TI - Community participation within a primary health care programme. AB - Based on experiences made in rural communities of Tanzania, aspects of community participation in schistosomiasis control within a primary health care (PHC) programme are discussed. Community participation is seen as prerequisite for PHC. Building up community participation can not be disease- or even symptom orientated, it must be community problem-orientated. The assessment of village priorities as they are recognized by the community governs any control strategy based on PHC. As schistosomiasis is often not first ranking among community problems, schistosomiasis control must become part of a multisectorial approach to improve community health. This process can initiate and ensure community participation and may lead to cost-effective control measures within PHC. PMID- 3092335 TI - Knowledge, perceptions and health behavior pertaining to Schistosoma mansoni related illness in Machakos district, Kenya. AB - This study on indigenous knowledge, preferences and health behavior among households and traditional healers in an area endemic Schistosomiasis mansoni in central Kenya showed that the population used modern and traditional health services interchangeably for intestinal illness with similar results. Cultural, economic and social factors in the utilization of different health services were identified. Antischistosomal treatment in the study population resulted in higher cure rates than those observed either hospital and health center treatment or the use of herbal medicines. Kamba knowledge and perceptions of the causes of water related intestinal illness, several types of preventive behavior and the role of women as health promoters are evaluated. The utilization of these observations in schistosomiasis control programs using the primary health care approach was discussed. PMID- 3092336 TI - Snail control in relation to a strategy for reduction of morbidity due to schistosomiasis. AB - The control of schistosomal disease is now distinctly feasible in endemic situations where a capable health care delivery system exists. Effective integrated control of schistosomiasis morbidity, within available resources at national level, is now being carried out in many countries. The control of snail hosts by chemical, environmental and/or biological means can still play a significant supporting role in many endemic situations. Today, however, as compared to earlier decades when disease control procedures were far less advanced, there is need for reappraisal of snail host control strategies to ensure that objectives are now correctly set, that the potential operational mechanisms are carefully chosen under the headings of desirability, feasibility and cost-effectiveness and that implementation and evaluation of the operations have, as far as possible, both theoretical and practical validity. Nowadays snail host control procedures must be intimately linked to knowledge of transmission sites and seasonal patterns, focal and periodic transmission being the rule rather than exception; in particular, they must be associated with local schemes for the delivery and evaluation of population based chemotherapy campaigns. PMID- 3092337 TI - Schistosomiasis in a mining area: intersectoral implications. AB - The high prevalence (greater than 90%) and intensity of infection (50% of those infected excreted greater than 600 eggs per gram of faeces) of schistosomiasis in a tin mining area in eastern Zaire is related to extensive man-made ecological changes and intensive man/water contact. Construction of latrines, water supply and availability of diagnosis and treatment through occupational health services have been used in control efforts. The integration of environmental measures is limited by their high costs. The control of schistosomiasis in this area of intense transmission would require repetitive chemotherapy and other measures which are beyond available resources. PMID- 3092338 TI - Simplified data collection and analysis in a Schistosoma mansoni endemic area. AB - Proper data collection and analysis is one of the important factors to successfully carry out the surveys in Schistosoma mansoni endemic areas. The data needed can be divided into three main categories i.e. pre-survey, during the survey and follow up data. Various factors are considered important for correct data collection. Without proper data collection and analysis, future planning of the programme, monitoring of the operation, modifications, correct interpretation of the results and evaluation of the programme cannot be done. Hence correct decision on the future of the programme cannot be made by professional, technical and administrative authorities. Data collection forms could be designed as required, keeping in mind the objectives of the programme. PMID- 3092339 TI - Monitoring and evaluating schistosomiasis control within a primary health care programme. AB - Approaches for monitoring and evaluation of schistosomiasis control within primary health care (PHC) programmes are discussed on the basis of experiences in rural Tanzania. Feedback is regarded as an essential element of evaluation. It ensures community participation and strengthens the PHC approach. Monitoring, evaluation and feedback depend on the type of control strategy chosen. The strategy in turn is governed by the epidemiological factors and the politico socioeconomic situation of the setting where schistosomiasis control is envisaged. Simple methods for monitoring control activities at community level exist and are being tested on a long-term basis. They relate to epidemiologically relevant parameters, such as prevalence, incidence and morbidity, and they can be handled by members of a community, particularly village health workers and/or staff of a dispensary. Most of the data collected by the community or its segments allow immediate feedback and form the basis for new or adopted strategies. PMID- 3092340 TI - Are measurements of intensity of infection or morbidity necessary to evaluate schistosomiasis control within PHC? AB - Techniques that can be used to monitor changes in morbidity in large scale control schemes carried out through the PHC structure by a local health administration differ from those that can be used in well funded, small scale research programmes. Above all they must be cheap, simple, rapid and objective. They should demonstrate the effects of intervention soon after it has taken place and be directed to phenomena that have high prevalences. Monitoring of liver and spleen size in S. mansoni foci to some extent meets these criteria but can only be seen as an adjunct to quantitative microscopy. Urinalysis with reagent strips, or even simpler methods, may have a more important role in evaluating control of urinary schistosomiasis and practical constraints may make it easier to carry out than quantitative microscopy. However, the latter conveys more information and is of greater value in planning and urinalysis must be seen as an inadequate substitute for quantitative microscopy. PMID- 3092342 TI - [Anterolateral meningocele]. AB - The author gives a detailed description of diagnosis and differential diagnosis of a thoracic lateral meningocele associated with known neurofibromatosis (von Recklinghausen's disease), using plain roentgenography, myelography and computed tomography. PMID- 3092341 TI - Immune suppression to Trypanosoma cruzi antigens is associated with infection but not immunisation. AB - Immune responses to Trypanosoma cruzi antigens in infected (C57BL/6 X C3H)F1 hybrid mice were followed throughout the acute infection and into the chronic phase, and compared to immune response kinetics of immunised, but uninfected, mice of the same strain. Anti T. cruzi antibody was detected by day 10 in infected animals and by day 5 in antigen sensitised mice. Animals sensitised with T. cruzi antigens showed strong delayed type hypersensitivity (DTH) responses to T. cruzi antigens. Infected animals were non-responsive during acute infection and immediately after resolution of parasitaemia, but showed similar responses to immunised animals during the chronic phase. The cell mediated immune response to T. cruzi antigens was assessed in vitro lymphocyte transformation tests. Antigen sensitised mice were responsive to antigen at all time points. Infected animals showed reduced responses during acute infection but attained levels similar to antigen-sensitised mice around 60 days post infection. The results suggest immune suppression during the acute phase is related to infection, but that, unlike other trypanosome infections, suppressor cell-inducing antigens are not present in the T. cruzi antigen preparations tested. PMID- 3092343 TI - A prospective study of high-frequency auditory function in patients receiving oral neomycin. AB - Orally administered, neomycin is reported to cause ototoxicity rarely. Most reports on hearing loss due to oral neomycin have been case studies. One prospective study of a pediatric sample demonstrated a significant loss of hearing in the frequency range of 2 to 8 kHz in 9 of 17 children. To our knowledge there are no published prospective studies on this type with adult samples and therefore little is known of the true incidence or nature of ototoxicity from oral neomycin. This prospective study presents the results of long-term use of oral neomycin in 30 adult subjects. Hearing sensitivity was serially monitored in the frequency range 250-20,000 Hz. Two of the 30 subjects subsequently revealed ototoxicity. Thus the results of this investigation suggest that clinical use of oral neomycin implies relatively little risk of ototoxicity. PMID- 3092344 TI - Results of short- and long-term cimetidine treatment in patients with juxtapyloric ulcers, with special reference to gastric acid and pepsin secretion. AB - One hundred and seven patients with active juxtapyloric ulcers and a history of chronic ulcer disease were treated with cimetidine. After ulcer healing 67 patients were selected for medical management, testing the value of cimetidine maintenance treatment. Time to healing was shorter for patients with duodenal ulcers when compared with those with active prepyloric ulcers. Recurrences were fewer for patients with pure duodenal ulcer disease (DUD) when compared with those with active or previous prepyloric ulcer disease (PUD). Patients whose ulcers were slow to heal and those with active or previous prepyloric ulcers (PUD) required a higher dose of cimetidine for effective control of their disease. All patients with slowly healing ulcers (more than 6 weeks) relapsed with 400 mg cimetidine at night. Among patients with relapse 46% with DUD and 31% with PUD were controlled by increasing cimetidine to 400 mg twice daily. Tests of acid secretion were of no value in predicting the rate of ulcer healing or relapse rate. Pepsin secretion studies, however, were of predictive value for patients with DUD but of indeterminate value for patients with PUD. Long-term cimetidine produced a significant decrease in pentagastrin-stimulated pepsin secretion (without treatment) in both patients with and without relapse. No significant changes in acid secretion were observed. As a result of these studies we recommend a cimetidine maintenance dosage of 400 mg twice a day for all patients whose ulcers are slow to heal on 1 g cimetidine a day and in patients with prepyloric ulcer disease regardless of rate of healing. PMID- 3092345 TI - The effect of temperature and pH on the stability of human pepsin in stored gastric juice. A method to prevent activity loss. AB - The mechanisms controlling pepsin secretion are controversial. A contributory factor may be storage-dependent effects. We have studied the effects of temperature, pH, and storage time on human gastric pepsin. Gastric juice samples taken from three healthy volunteers under both basal and post-pentagastrin stimulated (6 micrograms/kg subcutaneously) conditions were separated into four aliquots. Each aliquot was titrated to pH 1, 4, or 6 or left at ambient pH. Aliquots were then stored at 4 degrees C or frozen at -70 degrees C and stored. On days 1, 3, 7, and 28 aliquots were removed and assayed by the kinetic albumin bromphenol blue method. In a second experiment we determined the effects of different concentrations of glycerol on the preservation of peptic activity. From these experiments we conclude that pepsin is unstable when stored frozen at low pH but not when stored above pH 2. This pH-dependent stability may explain the variable conclusions other workers report on optimal methods of storing gastric juice. In addition, we have confirmed the suitability of glycerol as a preservative of peptic activity and recommend that gastric juice be stored frozen with 11.5% glycerol. PMID- 3092346 TI - Characterization of Raji cell binding IgG in patients with metastatic breast cancer. AB - The aim of the present study was to isolate and characterize the immune complexes detected by the Raji cell assay in metastatic breast cancer. However, the Raji cell binding material could not be separated from monomeric IgG by Sephacryl S 300 gel chromatography in any of the 16 sera investigated. The parallel elution profile of monomeric IgG and the Raji cell binding activity suggested that anti Raji cell antibodies, rather than immune complexes of low molecular weight, were present in these sera. This was further substantiated by pepsin digestion of the Raji cell binding IgG fractions. The binding of F(ab')2 fragments was quantitatively comparable to the binding of undigested IgG, and the bound F(ab')2 fragments could be visualized by immunofluorescence at the cell membrane. The presence of antibodies against Raji cells was further confirmed by the complement dependent cytotoxicity assay. These antibodies did not react with untransformed lymphocytes and there was no correlation with anti-Epstein-Barr virus antibodies. The incidence of cytotoxic anti-Raji cell antibodies in breast cancer was 12% compared to 20% in malignant lymphoma, to 0% in normals and patients with degenerative cardiovascular diseases, and to 5% in patients with auto-immune diseases. PMID- 3092347 TI - Mannitol concentrations in blood plasma in connection with transurethral resection of the prostate using mannitol solution as an irrigating fluid. AB - Thirteen patients undergoing transurethral resections of the prostate (TURP) using iso-osmolar 5% mannitol as an irrigating fluid were studied. Mannitol was determined in serum (plasma), as were sodium, prostatic acid phosphatase protein (PAP) and osmolality as probable indicators of absorption of irrigating fluid. The plasma level of mannitol (mean 2.7 g/l = 15 mmol/l) immediately postoperatively, the increase in serum PAP (mean 93 micrograms/l) and the decrease in serum sodium (mean 8.7 mmol/l) all reflect the amount of irrigating fluid absorbed during TURP. The three variables are intercorrelated. The plasma osmolality was unchanged (mean -1 mosmol/kg). A small but constant fraction of mannitol was found in the erythrocytes 2 hours after the operation, amounting to about 3% of the simultaneous plasma concentration. The mean plasma half-life of mannitol was 127 min in the absence of uraemia. In two cases showing a slight increase in serum creatinine the half-lives were prolonged. An estimate of the volume of fluid absorbed was made from the observed plasma mannitol levels. A fluid absorption of up to 3 litres (mean 1.1 l) was found. A strong diuretic effect was observed in some cases when irrigation with mannitol was combined with i.v. furosemide. We conclude that the i.v. diuretic should be withheld until the extent of fluid absorption has been estimated. If the sodium concentration in the serum is largely unchanged immediately postoperatively, diuresis can be induced by an intravenous diuretic. PMID- 3092348 TI - Influence of various irrigation fluids on serum enzyme patterns following transurethral resection of the prostate. AB - Serum levels of a variety of enzymes were determined preoperatively and repeatedly postoperatively in a comprehensive biochemical study of 60 patients undergoing transurethral resection of the prostate (TURP). These patients were divided into four groups depending on the type of fluid used for irrigation during TURP. Prostatic acid phosphatase (PAP, analysed by radio-immunoassay) in serum showed a marked postoperative increase but wide inter-individual variation in all groups. It returned to normal within 24 to 48 hours. When water was used for irrigation, similar but less pronounced increases were observed for serum lactate dehydrogenase (LD, LD-1) and aminotransferases (ASAT, ALAT). This is interpreted as being due to an influx of irrigating fluid into the general circulation from the bladder through opened veins, by absorption from a perivesical accumulation or, in the case of PAP, also from the prostatic wound. The enzyme increases (other than PAP) may be due to their release from haemolysed red cells in the bladder or in a perivesical fluid accumulation, which conjecture is supported by the marked increase also seen in plasma haemoglobin. When iso osmolar fluids were used for irrigation signs of haemodilution, such as a postoperative decrease in serum sodium, were observed. Several of the variables studied may be used as markers to indicate the quantity of irrigating fluid absorbed during resection. Plasma haemoglobin, serum LD (or LD-1) in connection with water irrigation, serum sodium in connection with iso-osmolar fluid irrigation and serum PAP, regardless of the type of irrigating fluid used, are some practical suggestions for such markers. PMID- 3092349 TI - Antibodies to Enterobacteriaceae in ankylosing spondylitis. AB - Serological studies on ankylosing spondylitis (AS; N = 82) show that although statistically more AS patients than controls (N = 24) may possess elevated serum titres to enterobacteria such as Salmonella, Shigella and Yersinia, this does not necessarily imply enterobacterial involvement in AS, as other groups without enteritis or arthropathies that frequent health care facilities (N = 72) may also display this phenomenon, presumably due to increased exposure. Moreover, an inventory of all detectable antibody reactivities to the separated cell envelope antigens of five enterobacterial species suspected of involvement in AS (notably Enterobacter, Klebsiella, Salmonella, Shigella and Yersinia) failed to reveal statistical associations with AS. This might be explained, assuming that the aetiology of AS entails a set of enterobacteria rather than a few individual species. It is proposed that serological studies on AS should be supported by additional information, e.g. that of the faecal carriage, and that these combined studies encompassing other enterobacteria, in addition to Klebsiella, might be fruitful. PMID- 3092350 TI - The association between the lupus anticoagulant and cerebral infarction in systemic lupus erythematosus. AB - The lupus anticoagulant (LAC) is associated with the occurrence of thromboembolic complications. Assuming that thrombosis may underlie manifestations of the central nervous system (CNS) in patients with systemic lupus erythematosus (SLE), we studied 20 patients with SLE and CNS manifestations for the presence of LAC. In 8 patients (40%) including 4 with overt cerebral infarction, LAC was demonstrated. The 4 patients with LAC and cerebral infarction all had thrombocytopenia, 2 had a history of peripheral thrombosis, and one recurrent abortion. In the 4 LAC-positive patients without overt cerebral infarction, thrombocytopenia was present in 3, a history of thrombosis in 2, and fetal wastage in one. We conclude that LAC identifies within the CNS-SLE group a subpopulation of patients in whom CNS manifestations are caused by cerebral infarction. This subpopulation is further characterized by increased prevalence of thrombocytopenia, peripheral thrombosis and fetal wastage. A possible pathogenetic role of LAC may be related to a hypercoagulable state occurring in this subgroup of SLE patients. PMID- 3092351 TI - [Does the determination of basal TSH level replace the TRH test?]. AB - With the help of the newly developed "supersensitive" assays for thyrotropin it is possible to determine concentrations down to 0.03 mU/l. Patients with a manifest hyperthyroidism show, as a rule, very low TSH levels and they react not at all or only very weakly to TRH stimulation. Therefore, various authors have claimed that estimation of the basal TSH level is sufficient as a screening test for the exclusion of a hyperthyroidism. To check the reliability of this statement we determined the reference interval of the parameter "basal TSH". It is a log-normal distribution; the reference interval of healthy people (95. percentile) is 0.25-4.0 mU/l. The TSH response to TRH stimulation also follows a log-normal distribution, the reference interval being 3.0-20 mU/l. There is a poor correlation between both parameters (r = 0.83). Histograms of populations with reduced, normal, or increased reactivity to TRH stimulation show broad overlapping zones. A valid prediction (with a plausibility greater than 90%) of the TSH response to TRH stimulation is therefore possible in the extreme ranges only (less than 0.2 mU/l for reduced, greater than 5 mU/l for increased reactivity respectively). In between there is a wide "gray zone", where reliable prediction is not possible on the basis of laboratory data only (without clinical findings). PMID- 3092352 TI - The endocrine control of ovulation. PMID- 3092353 TI - Derivation and diversification of monoclonal antibodies. PMID- 3092354 TI - Activists rebuffed in monkey court case. PMID- 3092355 TI - Common mechanism of chromosome inversion in B- and T-cell tumors: relevance to lymphoid development. AB - An inversion of chromosome 14 present in the tumor cells of a patient with childhood acute lymphoblastic leukemia of B-cell lineage was shown to be the result of a site-specific recombination event between an immunoglobulin heavy chain variable gene and the joining segment of a T-cell receptor alpha chain. This rearrangement resulted in the formation of a hybrid gene, part immunoglobulin and part T-cell receptor. Furthermore, this hybrid gene was transcribed into messenger RNA with a completely open reading frame. Thus, two loci felt to be normally activated at distinct and disparate points in lymphocyte development were unified and expressed in this tumor. PMID- 3092356 TI - Inhibin-mediated feedback control of follicle-stimulating hormone secretion in the female rat. AB - The secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland is regulated by the interaction of hypothalamic and gonadal hormones. Recently, proteins termed inhibins that selectively suppress FSH secretion have been purified and characterized from the gonadal fluids of several species. Antibodies to a synthetic peptide encompassing the amino terminal 25 residues of the recently characterized porcine inhibin were used to develop a specific radioimmunoassay (RIA) for inhibin and to neutralize endogenous inhibin during the estrous cycle of the rat. The administration of 20 international units of pregnant mare serum gonadotropin (PMSG) stimulated the secretion of inhibin in intact immature female rats, whereas ovariectomy caused an abrupt decrease in plasma inhibin concentrations that were not prevented by the injection of PMSG. The infusion of a polyclonal antiserum to inhibin, from 12 noon on proestrus to 1 a.m. on the morning of estrus, as well as its acute intravenous injection during diestrus I or II, caused an increase in plasma FSH (but not luteinizing hormone) concentrations. These results support the hypothesis of a feedback loop between the release of ovarian inhibin and FSH in the female rat. PMID- 3092358 TI - [Cell proliferation in the carcinogenic process of tongue carcinoma in rats induced by 4-nitroquinoline-1-oxide. 2. Relation between morphology, microvascular architecture and cell proliferation in keratinized lesions and squamous cell carcinoma]. PMID- 3092357 TI - Human acute myeloid leukemia lines: models of leukemogenesis. AB - Human AML cell lines provide models to identify inducers of differentiation of leukemia cells. Future studies will probably examine the combination of inducers of differentiation. Induction of differentiation, although an exciting concept, remains only a potential therapeutic modality. Perhaps of even greater importance, the cell lines provide a useful model of cellular differentiation. We should learn what cellular events trigger cells to undergo terminal differentiation. Likewise, the role of oncogenes and other pivotal genes in normal differentiation and their alteration in leukemias will be determined. PMID- 3092359 TI - Predominance of Pseudomonas aeruginosa serotype 11, pyocin types 1 and 10 in Singapore. PMID- 3092360 TI - The spatial distribution of health resources within countries and communities: examples from India and Zambia. AB - "Between one country and another, one province and another and even one locality and another there will always exist a certain inequality in the conditions of life, which it will be possible to reduce to a minimum but never entirely remove", Friedrich Engels, 1875, Quoted from D. M. Smith's Where the Grass is Greener; Geographical Perspectives on Inequality. London, 1979. And it is true that there are wide disparities in the availability of welfare facilities including health at international, national, regional and inter-regional levels. At the same time such disparities are increasing over time. In terms of spatial distribution, not only the developing world but even developed countries such as the U.S.A. and the United Kingdom, face problems resulting from wide imbalances in the provision of welfare facilities. In this paper, an attempt has been made to study inequalities in the distribution of health facilities in India and Zambia. PMID- 3092361 TI - The economics and evaluation of dental care and treatment. AB - This paper is concerned with economic evaluation in dentistry. The potential for such evaluation is great, but has not been fully realised to date. A number of issues which are common to the existing literature are discussed, and particular attention is paid to the question of measuring dental health in economic appraisal. Directions for future research are presented. The paper concludes that the future for economic evaluation in dentistry is favourable and that there is a need for greater collaboration between economic and dental researchers in this area. PMID- 3092362 TI - Ethics and resource allocation: an economist's view. AB - This paper debates some of the issues involved in attempting to apply economic analysis to the health care sector when medical ethics plays such an important part in determining the allocation of resources in that sector. Two distinct ethical positions are highlighted as being fundamental to the understanding of resource allocation in this sector -- deontological and utilitarian theories of ethics. It is argued that medical ethics are often narrowly conceived in that there is a tendency for the individual, rather than society at large, to form the focal point of the production of the service "health care'. Thus medical ethics have been dominated by individualistic ethical coded which do not fully consider questions relating to resource allocation at a social level. It is further argued that the structure of the health care sector augments these "individualistic' ethics. It is also suggested that different actors in the health care sector address questions of resource allocation with respect to different time periods, and that this serves to further enhance the influence of "individualistic' ethical codes in this sector. PMID- 3092364 TI - Smoking and medical care expenditures--what we know and what we don't know. PMID- 3092363 TI - Validation of a decision model for triaging hypertensive patients to alternate health education interventions. AB - The ability to assign patients to the most appropriate program of intervention would improve patient outcomes and reduce health care costs. This paper evaluates specific potentials of triaging patients into various combinations of health education treatments. Blood pressure improvement among hypertensive patients was measured and the associated treatment cost and savings were compared. Triaging rules were formed empirically from the relationship between patient characteristics selected before the study was conducted and their achieved blood pressure control within each combination of interventions. Patients randomly assigned to seven combinations of three interventions were studied in contrast to patients in a randomized control group. A combination of all three interventions was the most effective program for the undifferentiated (random) patient population, achieving a 49% increase over 18 months in patients with blood pressure under control. By triaging, 51-91% increases in patients with controlled blood pressure were achieved. Educational history of the patients which is a fairly reliable measure was the most efficient triaging variable, showing a 91% increase in patients with blood pressure under control and a relative cost saving of about 400%. PMID- 3092365 TI - Polychlorinated biphenyls in the electrical machinery industry: an ethnological study of community action and corporate responsibility. AB - Environmental and occupational health problems cannot be understood through purely medical and epidemiological analyses, the social forces affecting biologically adaptive behavior must also be analyzed. Research on the political economy of health needs to generate an ethnology of community action relevant to the analyses of corporate structures for which it is best known. In studying the community of Pittsfield, Mass., where a General Electric plant is located, we encountered environmental and occupational health problems in just this context. This essay is, therefore, an effort to extend the political economy of health into the ethnological domain of community research. PMID- 3092366 TI - Elusive diagnosis of tuberculous peritonitis. AB - Four patients with tuberculous peritonitis were diagnosed at our hospital in one year. In two patients it was only after surgery for iatrogenic bowel perforation that the diagnosis was made. The difficulty in recognizing this illness in those patients prompted a review of cases in Arkansas over the past nine years. A total of 27 cases have been documented; in 14 the diagnosis was made after considerable delay or during surgery for another diagnosis. Tuberculous peritonitis should be considered in any patient with ascites and chronic abdominal pain. PMID- 3092367 TI - [Occupational rehabilitation of long-term psychiatric patients. A catamnestic study]. PMID- 3092368 TI - [Component nutrient mixtures in abdominal surgery]. PMID- 3092369 TI - [The long term administration of allopurinol in primary gout]. PMID- 3092370 TI - Evaluation of child health services at Gelukspan Community Hospital, Radithuso, Bophuthatswana, 1976-1984. AB - Since the independence of Bophuthatswana in 1977 many new services have been established. The policy of the Department of Health and Social Welfare to practise primary health care has been implemented step by step and special attention has been given to the well-being of infants and preschool children. During this period several parameters of child health have been monitored, such as mortality rates, nutritional status and immunization status. In a few years significant changes have taken place. PMID- 3092371 TI - Hypokalaemia after suxamethonium administration. AB - The effect of suxamethonium on serum potassium levels was studied in 20 black patients undergoing emergency surgery. All patients were resuscitated pre operatively to achieve a normal pH (range 7.35-7.45), normal electrolyte values (potassium range 3.5-4.5 mmol/l), and an adequate circulating blood volume using the criteria of systolic blood pressure in excess of 100 mmHg and a central venous pressure maintained at more than 2 cm H2O. Suxamethonium (approximately 0.8 mg/kg) was administered during a standard rapid intubation sequence for the induction of anaesthesia. In the adequately resuscitated emergency patient an induced respiratory alkalosis may prevent the rise in serum potassium previously reported with the use of suxamethonium. PMID- 3092372 TI - Graves' disease and selective resistance of pituitary thyrotroph to thyroid hormone. A case report. AB - A patient with Graves' disease who had inappropriately increased thyroid stimulating hormone (TSH) concentrations and TSH response to thyrotrophin releasing hormone is reported. No pituitary tumour could be demonstrated and the patient is considered to be an example of selective resistance of the pituitary thyrotroph to thyroid hormone action. PMID- 3092373 TI - [Usefulness of 2-mercaptoethanol sodium sulfonate (Mesnum) in the prevention of hemorrhagic cystitis in patients undergoing bone marrow transplantation]. PMID- 3092374 TI - [Determination of free kappa and lambda light chains in urine by immunoenzyme analysis]. PMID- 3092375 TI - [Qualitative and quantitative study of a DVI variant with anti-D in the serum]. PMID- 3092376 TI - Nutritional therapy for children with cancer. PMID- 3092377 TI - [Unusual multiple myeloma: biclonal gammopathy associated with hyperlipidemia]. PMID- 3092378 TI - [Repeated abortion associated with a lupus-type circulating anticoagulant]. PMID- 3092379 TI - Evaluation of a supplemental dental booklet for long-term care facilities. PMID- 3092380 TI - Nutrition during treatment of head and neck cancer. PMID- 3092382 TI - The ring fixation of T tubes. AB - By using a rubber ring for the attachment of the T tube to the abdominal wall, a secure approximation can be achieved. Slippage of the tube, which occurs when the T tube is tied directly with the suture material, can be eliminated. Stricture of the T tube can also be prevented. We have found this method to be successful and accidental dislodgement has not occurred. PMID- 3092381 TI - Comparison of isotonic and hypertonic fluids in resuscitation from hypovolemic shock. AB - Hypertonic electrolyte solutions provide effective fluids for resuscitation of burn patients and concurrent replacement of hemorrhage. Infusion of mannitol has also been advocated as a means of increasing cardiac output in acutely ill patients. Pigs which were bled to one-third of their blood volume were used in this random study of resuscitation with Ringer's lactate solution (RL), hypertonic saline solution (HSL) and RL with mannitol added (HMR) to give the same osmolality as HSL. Smaller volumes of the hyposmolar solution than of RL restored blood pressure and cardiac output. RL and HSL restored and maintained cardiac output more effectively than HMR. At 24 hours, HSL maintained blood pressure most effectively. PMID- 3092383 TI - Lateral thoracic meningocele. AB - A case of intrathoracic meningocele is reported, and 95 cases from the literature are reviewed. Thoracic meningoceles are usually associated with neurofibromatosis; nevertheless their etiology remains controversial. The authors postulate the role of spinal trauma in some patients and the origin of the meningocele from an abnormal prolongation of a nerve sleeve in nontraumatic cases. Thoracic meningoceles often are asymptomatic or produce radicular intercostal pain. Spinal computed tomography is the most useful investigation, particularly in the exploration of large meningoceles. Surgery is required in symptomatic cases and usually results in remission of the pain. PMID- 3092384 TI - Laser interactions with the cornea. AB - Principles of laser-tissue interactions in the eye are reviewed. Corneal structure and function are summarized, with particular regard for features related to laser treatment. A summary of argon and carbon dioxide laser techniques in the cornea is presented, followed by a review of studies on corneal response to ultraviolet radiation. A detailed description is then given of the characteristics of excimer laser tissue ablation. Potential applications of this process in corneal and keratorefractive surgery are reviewed. PMID- 3092385 TI - [Attachment of tooth fragments after fracture: preliminary report]. PMID- 3092386 TI - Cerebral blood flow during cardiopulmonary bypass in man: effect of arterial filtration. AB - Cerebral blood flow was recorded in 39 patients undergoing cardiac surgery by intraarterial injection of xenon 133. There were three subgroups of patients: 10 patients had a 20 micron arterial filter (Johnson) and 11 a 40 micron filter (Pall), and 18 had no arterial filtration. All patients had a 40 micron (Pall) filter in the coronary suction line. Significant changes in cerebral blood flow occurred during extracorporeal circulation (p less than 0.0001). For all patients cerebral blood flow increased from a resting prebypass level of 30 to 46 and 57 ml/100 g a minute during initial and stable hypothermic extracorporeal circulation respectively. Both measurements were obtained at 26 degrees C and the recordings were made on average 12 and 55 minutes after the extracorporeal circulation was started. During rewarming cerebral blood flow increased to 64, 53, 41, and 36 ml/g a minute at 31 degrees, 33 degrees, 35 degrees, and 37 degrees C respectively, and when measured four and 16 minutes on average after bypass it was 44 and 41 ml/100 g a minute. This general brain hyperperfusion was noticed in all patients with a high enough mean blood pressure to produce hyperaemia. Interposing 20 and 40 micron arterial filters reduced cerebral blood flow but did not prevent this hyperaemia. The cerebral autoregulation, which maintains a constant cerebral blood flow within wide limits of perfusion pressures, was not affected by arterial filtration. The lower limit of blood pressure at which a further reduction in blood pressure was followed by a reduction in cerebral blood flow was around 60 mm Hg in all three groups. PMID- 3092387 TI - Bronchoalveolar lavage in Waldenstrom's macroglobulinaemia with pulmonary infiltrates. PMID- 3092388 TI - Fibrinolytic activity and protein C in preeclampsia. AB - Various parameters of the fibrinolytic system and antigenic and functional protein C and its inhibitor were studied during normal pregnancy and in patients with preeclampsia. The fast acting tissue-type plasminogen activator inhibitor level was found to increase progressively during normal pregnancy. This increase was more evident in cases of severe preeclampsia (p less than 0.05). No variations were observed in protein C levels in normal pregnancies but a reduction in protein C level was noted in patients with severe preeclampsia (p less than 0.01). In preeclampsia, the protein C inhibitor level was higher than in normal pregnancy; it was also higher in normal pregnancy when compared to the control group. PMID- 3092389 TI - Blood platelet plasminogen activator inhibitor: two different pools of endothelial cell type plasminogen activator inhibitor in human blood. AB - An assay for plasminogen activator inhibitor in human platelets is described. With this assay we find an average value of 6.8 X 10(-8) IU/platelet (S.D. = 3.0 X 10(-8); n = 20) in a healthy population. We characterized the PA-inhibitor from platelets and identified it as endothelial cell type plasminogen activator inhibitor, by its immunologic and functional properties. Besides the plasma pool of plasminogen activator inhibitor with a very high turnover rate, platelets constitute a second pool of plasminogen activator inhibitor in the circulation of the same order of magnitude. The two different pools of plasminogen activator inhibitor might have a different physiologic function. PMID- 3092390 TI - Increase in plasma concentration of plasminogen activator inhibitor, fibrinogen, von Willebrand factor, factor VIII:C and in erythrocyte sedimentation rate with age. AB - Elderly patients have previously been shown to have an increased plasma concentration of tissue plasminogen activator (t-PA) antigen (t-PA Ag). Since the concentration of t-PA Ag depends on both free t-PA and t-PA complexed with inhibitors, mainly plasminogen activator inhibitor (PA inhibitor), we have investigated the relationship between the plasma concentration of PA inhibitor and age in 20 elderly and 20 young individuals. Elderly individuals showed a slight increase in PA inhibitor, in parallel with increase on others, acute-phase proteins, fibrinogen, von Willebrand factor, factor VIII:C, and the erythrocyte sedimentation rate. The increase in PA inhibitor as well as other acute-phase proteins in the elderly may be significant in relation to the increased incidence of thrombotic disease. PMID- 3092391 TI - Monoclonal antibodies against human high molecular weight urinary urokinase: application for affinity purification of urinary prourokinase. AB - Monoclonal antibodies against urinary urokinase were obtained by immunizing mice with purified human high molecular weight urokinase. Five antibodies were selected and denominated MPW1UK, MPW2UK, MPW3UK, MPW4UK, and MPW5UK, respectively. All selected antibodies reacted with high and low molecular weight urokinase. Cleavage of the low molecular weight paranitroanilide substrate pyro Glu-Gly-Arg-pNA by urokinase was not inhibited by the antibodies and only one antibody (MPW5UK) inhibited plasminogen activation by urokinase. The ability of MPW5UK to bind to coated urokinase was 100-fold higher than that of the other antibodies. MPW5UK was used to prepare an immunosorbent for the purification of urokinase antigen from freshly voided crude urine. One-chain prourokinase was separated from two-chain urokinase by chromatography of the urokinase antigen containing mixture on agmatine Sepharose. As judged by SDS gel electrophoresis one-chain prourokinase as well as two-chain urokinase were purified to apparent homogeneity by this two-step procedure; the yields were 18% and 47% for single chain prourokinase and two-chain urokinase, respectively, as calculated from total urokinase antigen contained in the starting material. PMID- 3092392 TI - Platelet behaviour in non-insulin-dependent diabetes--influence of vascular complications, treatment and metabolic control. AB - Platelet-rich plasma was prepared from 47 patients with non-insulin-dependent diabetes treated with glibenclamide and metformin, and 21 controls. The release of radio-labelled 5-hydroxytryptamine in response to aggregating agents (adenosine diphosphate, adrenaline and sodium arachidonate), and the effects on release of a selective thromboxane inhibitor (UK-34787) were investigated. Subsequently, 20 of the diabetic subjects were chosen at random for treatment with insulin; the remainder continued to take tablets. Platelet studies were then repeated, in all patients, after 4 and 6 months. The results showed an association between platelet behaviour and the presence of vascular complications, and were consistent with previous observations of reduced platelet reactivity in patients taking sulphonylureas. There was no correlation of platelet reactivity with blood glucose, glycosylated haemoglobin or lipid levels. PMID- 3092393 TI - The von Willebrand factor in myocardial infarction and unstable angina: a kinetic study. AB - Recent studies have demonstrated elevations of von Willebrand Factor following acute myocardial infarction (AMI). In order to determine if this parameter may serve as a marker for AMI, we tested the blood levels of vWF and Factor VIII:C in 28 patients with AMI, 9 patients with unstable angina, 7 patients with atypical chest pain, and 25 healthy volunteers. The level of ristocetin cofactor activity of vWF was between 70 and 144% in the control group. In patients with AMI, the mean level of this activity was 175% on the first day following infarction, rose to a peak of 270% on the fifth and sixth days, and was still significantly greater than normal in all patients on the 14th day. The vWF:Ag level closely paralleled the rise of ristocetin cofactor activity of vWF, with a peak of 336% on day 5. FVIII:C was not significantly changed. No significant elevation of vWF was observed in patients with unstable angina. The ristocetin cofactor activity of vWF and vWF:Ag thus are sensitive biochemical indicators for recent AMI, and may serve as useful markers for up to 14 days following infarction, when the traditional enzymes have returned to normal levels. PMID- 3092394 TI - Modulation of arachidonic acid metabolism in human endothelial cells by glucocorticoids. AB - To learn whether glucocorticoids inhibit prostaglandin (PG) production in vascular endothelial cells, we investigated the effects of glucocorticoids on PG synthesis by cultured human umbilical vein endothelial cells (EC). Pretreatment of EC with dexamethasone (DX, 10(-9) to 5 X 10(-5) M) caused a dose-dependent inhibition of PGI2 production when PG synthesis from endogenous arachidonate was stimulated by human thrombin (0.25-2 U/ml) or ionophore A 23187 (1-5 microM). The inhibition was detectable at 10(-7) M DX and maximal at 10(-5) M (4.0 +/- 0.7 vs. control: 7.7 +/- 1.9 ng/ml, mean +/- S.D., P less than 0.01). The production of PGE2 and the release of radiolabelled arachidonate (AA) from prelabelled cells were similarly inhibited. Prolonged incubation of EC with glucocorticoids was required to inhibit PG production or arachidonate release: ranging from 8% inhibition at 5 h to 44% at 38 h. In contrast, prostaglandin formation from exogenous AA was not altered by DX treatment. When thrombin or ionophore stimulated EC were restimulated with exogenous AA (25 microM), DX-treated cells released more PGI2 than control cells (5.7 +/- 0.5 vs. 4.1 +/- 0.6 ng/ml, P less than 0.01). Both the decrease in PGI2 production after thrombin/ionophore and the increase after re-stimulation with AA were blunted in the presence of the protein synthesis inhibitor cycloheximide (0.1-0.2 micrograms/ml). Thus, incubation of EC with glucocorticoids inhibits PG production at the step of phospholipase activation. The time requirement for these steroid effects and their blunting by cycloheximide are consistent with the induction of regulatory proteins, possibly lipocortins, in endothelial cells. PMID- 3092395 TI - Monoclonal antibodies towards the fast inhibitor of tissue plasminogen activator from human plasma and serum. AB - Hybridoma cells were produced by fusing mouse myeloma cells (SP 2/0-Ag 14) with spleen cells from a Balb/c mouse, previously immunized with the partially purified complex between tissue plasminogen activator (t-PA) and its fast inhibitor from human plasma (serum). Screening with a radioimmunoassay revealed a number of hybridomas secreting antibodies directed towards the complex. Of these, about 1/3 reacted both with the complex and t-PA, whereas about 2/3 reacted only with the complex. Three of the latter hybridomas, producing antibodies directed towards the inhibitor-moiety in the complex have been cloned and the antibodies were studied in detail. PA-inhibitor activity in plasma or serum and t-PA/PA inhibitor complex could be specifically adsorbed on all three insolubilized monoclonal antibodies (MC1, MC2 and MC3). None of the antibodies seems to be directed against structures of vital importance for the functional activity of the PA-inhibitor. In accordance with this finding the antibody with the highest avidity (MC1) reacts equally well with the PA-inhibitor alone or in complex with t-PA. A radioimmunoassay was developed with this antibody and significant displacement was obtained with samples with PA-inhibitor concentrations above 2 AU/mL. In 13 plasma samples with different levels of PA-inhibitory activity a significant correlation was obtained when comparing this activity with the PA inhibitor antigen as measured with the radioimmunoassay (r = 0.88). PMID- 3092397 TI - Factor VIII lability, protein C and other vitamin K-dependent proteins. AB - The stability of factor VIII was studied in plasmas from patients on long-term warfarin therapy. The percent residual factor VIII activity (F.VIII:C) after incubation at 37 degrees C for 4 hr was higher in warfarinized patients than in normal subjects; 76.9 +/- 10.8% (mean +/- SD) of the initial F.VIII:C in the patients versus 61.6 +/- 5.8% in normal subjects (p less than 0.001). On the whole, neither protein C nor vitamin K-dependent coagulation factors except factor VII activity (F.VII:C) correlated with the residual F.VIII:C. There was a negative and weak correlation between the residual F.VIII:C at 4 hr and either the initial F.VIII:C or F.VII:C. Another experiment using protein C depleted plasma showed a relatively enhanced stability of F.VIII:C in the protein C deficiency. These results indicate that factor VIII is more stable in warfarinized plasma, and that protein C and vitamin K-dependent coagulation factors are not the sole, main factor responsible for such a phenomenon. PMID- 3092396 TI - Inhibition of tissue-type plasminogen activator in plasma of women using oral contraceptives and in normal women during a menstrual cycle. AB - Tissue-type plasminogen activator (t-PA) inhibition in plasma was assessed in 15 normal women and in 10 women using oral contraceptives (OC) containing 30 micrograms ethinyl oestradiol and 150 micrograms levo-norgestrel. The levels of t PA inhibition were significantly lower in the OC group with marked fluctuations related to the hormone cycle. Normal women had only minor fluctuations. PMID- 3092398 TI - The multimeric structure of plasma F VIII:RAg studied by electroelution and immunoperoxidase detection. PMID- 3092399 TI - The influence of HLA phenotypes on the response to parenteral gold in rheumatoid arthritis. AB - One hundred and ten patients with rheumatoid arthritis (RA) were studied for a possible influence of HLA phenotypes on the reaction to parenteral gold in the first 6 months of treatment, in terms of both clinical response and toxicity. Frequencies of HLA-B8 and -DR3 were significantly increased in patients who responded excellently to gold treatment as compared with non-responders (p = 0.04 for both antigens). On the other hand, for HLA-DR7 there was a tendency for increased frequency in non-responders versus excellent and moderate responders (p less than 0.03; Pc = n.s.). Drug toxicity was higher in excellent than in non responders (p less than 0.04), being exceptionally high in male excellent responders (85% versus 33% in females, p less than 0.01), probably due to the increased frequency in B8 and DR3 in the excellent responder group as a whole and in the excellent responder males in particular. We conclude that HLA antigens B8 and DR3 co-determine both toxicity and excellent clinical response to parenteral gold, whereas the presence of DR7 is possibly associated with non-response. In addition, we found sex differences in reaction to parenteral gold, which may be related to an increased frequency of HLA-B8 and -DR3 in male RA patients. PMID- 3092400 TI - Procuticle proteins and chitin-like material in the inner epicuticle of the Drosophila pupal cuticle. AB - The inner (protein) epicuticle of the pupal cuticle of Drosophila is shown to contain at least two hydrophobic proteins (19 and 21 kD) that are also present in the outer procuticle lamellae. An N-acetylglucosamine-containing carbohydrate is also present in the inner epicuticle. This represents the first attempt to characterize the non-lipid components of an insect epicuticle. PMID- 3092401 TI - Renal toxicity of propyleneimine: assessment by non-invasive techniques in the rat. AB - The nephrotoxicity of three different dose levels of propyleneimine (10, 20 and 30 microliter/kg body wt) administered intraperitoneally to rats was studied and 20 microliters/kg body weight was found to be the most appropriate sublethal dose. Injection of propyleneimine (10 microliters/kg body wt) produced a small rise in N-acetyl-beta-D-glucosaminidase (NAG) activity, minor histological damage but no change in urine volume. Six rats were injected with 20 microliters/kg body weight, and urine was collected over the following 16 days. An immediate increase in urine volume, osmolality together with a concomitant decrease in specific gravity, was accompanied by a small increase in creatinine excretion and a more marked increase in the sodium and potassium content of urine after the administration of the nephrotoxin. NAG activity increased immediately and peaked on day 3, the activity remained elevated until day 12 when it fell to near normal levels. The activity of both beta-D-galactosidase and beta-D-glucosidase increased 9 days after administration of the nephrotoxin. In contrast, no consistent change was found in the excretion of the brush border marker enzymes, leucine aminopeptidase (LAP), alanine aminopeptidase (AAP) or alkaline phosphatase (ALP). Proteinuria increased sharply the day after injection and remained abnormal. Increased urinary albumin excretion and the predominance of low molecular weight proteins was demonstrated by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. Evidence is presented that propyleneimine exerts its early toxic effect on the renal papilla. PMID- 3092402 TI - Endocrinology and suicide. AB - The data accumulated so far suggest several tentative conclusions. First, thyroid and adrenal gland disease unquestionably can produce severe mental disturbances. Most of these are "organic" in nature, but depressive symptoms are common as well. A connection between these diseases and suicide has not been established, however. Research cannot really address this possibility adequately, since these studies are difficult, if not impossible, to do in the postmortem state at this time. Ways should continue to be sought to overcome this problem. Clinically, it seems advisable to treat all depressed, suicidal persons with the same caution, whether they have diseases of these endocrine systems or not. The differences in responsiveness of the thyroid and adrenocortical systems among depressed and perhaps truly suicidal persons are of greater theoretical as well as practical clinical interest. The TRH-TSH test and the DST may not be as specific as once thought. Nonetheless, the abnormalities do occur with regularity in specific subgroups of depressed patients. It is far too early to stop research on the DST or the TRH-TSH test. Clinically, however, it is premature to make important management decisions about suicidal patients based on these test results. At this time, we really have no means of pinpointing the persons who will eventually suicide. The hope that they may someday provide valid data for assessing real suicide potential is there, and clinicians should stay informed in this arena. Until that day comes, though, we must continue to exercise caution regarding our clinical judgments and to live with their uncertainties. PMID- 3092403 TI - [Cavity lining materials today. Their use by Swiss dentists]. PMID- 3092404 TI - [Nearly 100 year history of De Trey Dentsply. The largest worldwide dental undertaking]. PMID- 3092405 TI - [100 years of dentistry. KaVo Dental. For 76 years engaged in development and research for dental medicine and dental technology]. PMID- 3092406 TI - [50 years of Kulzer. From the 1st heat-polymerizable synthetic denture resins to marginal fracture-free resin metal bonds]. PMID- 3092407 TI - Carbamazepine drug interactions. AB - Carbamazepine (CBZ) is commonly prescribed as an anticonvulsant or for the pain of trigeminal neuralgia. The potential for clinically important drug interactions exists because CBZ may induce the hepatic metabolism of other drugs or, conversely, other drugs may induce or inhibit the metabolism of CBZ. Studies and case reports demonstrate that CBZ may accelerate the metabolism of phenytoin, phenobarbital (PB), primidone, valproic acid, and warfarin. Likewise, phenytoin, PB, and primidone may increase the hepatic metabolism of CBZ. Inhibition of the metabolism of CBZ has been caused by triacetyloleandomycin, erythromycin, propoxyphene, isoniazid, and cimetidine. Future investigations will document the clinical significance of the CBZ interactions as well as reveal new interactions. PMID- 3092408 TI - Measurement of tocainide in serum by capillary gas chromatography. AB - A rapid and simple analytical method is described for the determination of tocainide in serum using flame ionization capillary gas chromatography. Following a single extraction with chloroform, tocainide is quantitated on an OV-17 bonded fused silica column, utilizing orphenadrine as internal standard. No interference was detected from endogenous substrates, tocainide metabolites, or other commonly used antiarrhythmic drugs. The lowest detectable tocainide concentration by this method is approximately 0.2 mg/L of serum, which is sufficiently sensitive for therapeutic monitoring. Utilizing temperature programming, this method for tocainide is applicable for several antiarrhythmic drugs. PMID- 3092409 TI - Influence of tube type, storage time, and temperature on the total and free concentration of valproic acid. AB - The influence of storage conditions on the total and free concentration of valproic acid (VPA) was studied in six normal male subjects who ingested 750 mg of VPA (3 X 250 mg Depakene capsules; Abbott Laboratories). Blood samples were collected in various types of Vacutainer tubes (red top, no additives; green top, sodium heparin; blue top, sodium citrate; and purple top, EDTA) 2 h post administration of VPA. Either these samples were centrifuged immediately or stored for various periods of time at room temperature or refrigerated, or the supernate was frozen prior to analysis. Free VPA samples were obtained utilizing the Amicon ultrafiltration system. All VPA samples were analyzed by gas-liquid chromatography. Total VPA concentrations obtained from plasma collected with sodium citrate were lower (p less than 0.05) than either serum or plasma collected with other anticoagulants. There were no differences (p greater than 0.05) in total or free VPA concentrations between samples collected in serum or in plasma collected with heparin or EDTA. Storing samples for 96 h at room temperature did not alter the total VPA concentrations but was found to increase the free fraction of VPA (p less than 0.05). The refrigeration or freezing of the supernate from the blood samples for 7 days did not alter (p greater than 0.05) the total or the free fraction of VPA. The results of this study demonstrate that total and/or free VPA may be collected from either serum or plasma, provided sodium citrate is not used to collect plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092410 TI - Valproic acid-amitriptyline interaction in man. PMID- 3092411 TI - The contribution of large granular lymphocytes to B cell activation and differentiation after T-cell-depleted allogeneic bone marrow transplantation. AB - Immunoglobulin and specific antibody levels are well maintained in the recipients of T-cell-depleted allogeneic bone marrow transplants (BMT), even though up to 99% of mature T cells are removed from the donor graft. For 3-8 weeks after the procedure, natural killer (NK) cells with an activated pattern of target cell killing have been shown to circulate in the recipient. This study investigates whether these recipient NK cells spontaneously secrete lymphokines that modulate B cell function in a way analogous to that of in-vitro-activated NK cells from normal individuals. Large granular lymphocytes (LGLs) (which contain a high proportion of NK cells) have been prepared from the peripheral blood of 11 recipients of T-cell-depleted major-histocompatibility-complex-matched allografts. In the first 4-6 weeks after BMT these LGLs were found spontaneously to secrete interleukin 2, interferon gamma and B cell differentiation factor. While secretion of these factors declines by 20-24 weeks after BMT, the quantities are still greater than those seen from control donors. Patient LGLs are also able to activate autologous (donor) B cells, rendering them potentially responsive to the secreted factors. It appears likely that activated NK cells (or LGL) play a significant role in maintaining B cell function in vivo after T-cell depleted BMT. PMID- 3092412 TI - Transplantation of fetal fibroblasts and correction of enzymatic deficiencies in patients with Hunter's or Hurler's disorders. AB - An attempt was made at correcting the specific lysosomal enzyme deficiencies in 7 children with Hunter's or Hurler's diseases by transplantation of fetal fibroblasts. In spite of pretreating the young patients with stored blood, following a procedure employed successfully to avoid rejection of kidneys from incompatible donors, the use of serum-free media for culturing the cells before being harvested and incubation of the cells with chorionic gonadotrophin, the transplantation of fetal fibroblasts was not associated with biochemical or clinical changes. None of the seven patients showed immune reactions against the transplanted cells, HLA antigens, or the missing enzymes. PMID- 3092414 TI - A technique for heart-lung transplantation in mice. PMID- 3092413 TI - Inhibition of anti-CD3 (T3) antibody-induced activation of T cells by cyclosporine. PMID- 3092416 TI - Cardiopulmonary involvement rare in severe Schistosoma japonicum infection. AB - In a prospective study, 65 consecutive patients hospitalized with Schistosoma japonicum infection were evaluated for evidence of cardiopulmonary involvement. Thirty-two patients had evidence of severe liver dysfunction while 11 patients had portal hypertension only. Of these 43 patients with hepatosplenic disease, only one patient had pulmonary hypertension. Cardiopulmonary involvement is relatively uncommon in severe S. japonicum infections. PMID- 3092415 TI - Hemorrhagic fever virus infections in an isolated rainforest area of central Liberia. Limitations of the indirect immunofluorescence slide test for antibody screening in Africa. AB - Serum samples from 119 healthy individuals and 106 epilepsy patients inhabiting Grand Bassa County, Liberia, were tested for antibodies to hemorrhagic fever viruses (HFV) by indirect immunofluorescence. E6 Vero cells infected with Lassa fever virus (LAS), Rift Valley Fever virus (RVF), Congo Hemorrhagic Fever virus (CON), Marburg virus (MBG) and the Ebola (EBO) virus strains Mayinga (May) and Boniface (Bon) were used as antigen. To obtain reproducible and specific test results sera had to be absorbed extensively with uninfected E6 Vero cells, tested for reactivity to both virus infected and uninfected E6 Vero cells and read "blindly" by two independent observers. Antibodies to EBO were shown to be highly prevalent (13.4%) in the population of this rainforest area, while prevalences of antibodies to LAS (1.3%), RVF (0.4%) and MBG (1.3%) were much lower. No correlation between past HFV infection and post-encephalitic epilepsy or other reported febrile illnesses could be established. PMID- 3092417 TI - Laboratory transmission of Schistosoma mansoni in brackish waters; survival and infectivity of cercariae. AB - Schistosoma mansoni cercariae were exposed to various dilutions of sea water, both in the absence and in the presence of mice. It was found that whereas 100% and 75% sea water were lethal to the parasites, the parasites survived in lower concentrations of sea water. The lower the concentration the longer was the survival time. Similarly, the rate of infection of mice decreased as the concentration of the sea water increased. PMID- 3092418 TI - Distribution of the adult lactase phenotypes in Turkey. AB - The adult lactase phenotype, lactose absorber or malabsorber, was determined using the lactose tolerance test with breath hydrogen assay in a group of young, healthy, male Turks. Out of a total of 470 subjects, 135 (28.7%) were lactose absorbers and 335 (71.3%) lactose malabsorbers. The frequency of the 'lactase suppression gene' in this population sample was 0.844 (S.D. 0.012). The frequency of lactase suppression in Turkey is intermediate between that in southeast Europe and that in agricultural Arab populations and thus compatible with a genetic cline extending from Europe to southwest Asia. PMID- 3092419 TI - Aflatoxins in the livers of children with kwashiorkor in Ghana. AB - Autopsy liver specimens from 22 kwashiorkor children in Ghana were analysed for the presence of aflatoxins using both high performance liquid chromatography and thin layer chromatography. Aflatoxin B1 was found in the livers of 20 subjects and aflatoxicol in the livers of the remaining two subjects. These results confirm previous findings of aflatoxin B1 and aflatoxicol in the livers of children with kwashiorkor and provide further evidence of associations between these toxic compounds and kwashiorkor which might have relevance to the aetiology and pathogenesis of this disease which as yet remain mysterious. PMID- 3092420 TI - [Plaster of paris compared with Hexcelite. A prospective, randomized, cost benefit analysis of below-the-knee casts]. PMID- 3092421 TI - [Urinary incontinence. Occurrence and treatment in a department of long-term care]. PMID- 3092422 TI - [Outbreak of gonorrhea caused by penicillinase-producing gonococcus in Arhus 1983]. PMID- 3092423 TI - [Familial neuroblastomas. Predictors of heredity]. PMID- 3092424 TI - [Hiccup. The physiopathological basis for treatment with special reference to valproate in therapy-resistant episodes]. PMID- 3092425 TI - [Hyperphenylalaninemia and prematurity]. PMID- 3092426 TI - [The course of admission and discharge in a department for long-term care. Illustrated by a prospective study and 6-month follow-up]. PMID- 3092427 TI - Intravesical chemotherapy: in vitro studies on the relationship between dose and cytotoxicity. AB - The relative importance of two variables, drug concentration and period of exposure, in relation to the therapeutic potential of intravesical chemotherapy was examined in an experimental system. A human bladder cancer cell line was exposed to a range of concentrations of the four drugs commonly used to treat superficial bladder cancer (adriamycin, epodyl, mitomycin-c, thiotepa) for periods of 30, 60 and 120 min. An exponential relationship was observed between clonogenic cell kill and both drug concentration and period of exposure. Thus, under the experimental conditions employed, cytotoxicity is proportional to dose (i.e. concentration X period of exposure). These two variables are of equal importance in relation to tumor cell kill, indicating that maximum therapeutic benefit may be obtained by using the highest concentration achievable for as long as the patient can retain the instillate, bearing in mind the potential increase in toxicity to the patient and the cost. PMID- 3092428 TI - [Endoprosthesis of the hip joint]. PMID- 3092429 TI - [Carbon dioxide laser in the treatment of hepatic echinococcosis]. AB - Laser was used in 14 patients for the treatment of surface of the residual cavity after excision of Echinococcosis cysts. The author notes positive sides of this method. PMID- 3092430 TI - [Comparative evaluation of specific laboratory methods of diagnosing echinococcosis]. AB - On the basis of a considerable material the authors make an evaluation of complex diagnostics of hydatid Echinococcosis of various localizations with the help of Casoni reactions, latex agglutination, double gel diffusion and indirect hemagglutination. The Casoni reaction is considered to be most reliable and simple among specific methods of diagnostics of Echinococcosis. It gave good results in mass prophylactic examinations of the population. The immunological methods of diagnostics of hydatid Echinococcosis are most reliable, the reaction of indirect hemagglutination having the greatest resolving power. PMID- 3092431 TI - Henneguya exilis Kudo associated with granulomatous branchitis of channel catfish Ictalurus punctatus (Rafinesque). AB - Outbreaks of a chronic branchitis in channel catfish Ictalurus punctatus (Rafinesque) were observed on four fish farms throughout the state of California from November 1982 to April 1984. Severe granulomatous inflammation of the gill filaments with necrosis of the cartilage of the gill ray and diffuse epithelial hyperplasia, resulting in extensive fusion of gill lamellae, was present on histologic examination of gill specimens from 35 out of 44 fish examined. Numerous, small trophozoites morphologically consistent with presporogonic myxosporean parasites were consistently associated with the inflammatory process. Mature spores of Henneguya exilis Kudo were present in large numbers in gill specimens from two fish and only occasionally in 22 others. Similar cases referred to as "Hamburger Gill Disease" or "proliferative gill disease" have been known to occur in the south-central United States. This report describes the morphologic changes of this condition and discusses its possible pathogenesis. PMID- 3092433 TI - Theileria taurotragi in Zambia. AB - Theileria sp. (Bwengwa) of low virulence was isolated by feeding R. appendiculatus ticks collected from the field on a susceptible calf and subsequently transmitted between cattle by R. appendiculatus ticks- Theileria sp. (Bwengwa) was shown to be T. taurotragi on parasitological, clinical and serological grounds. T. taurotragi is the fourth Theileria sp. shown to be present in Zambia. PMID- 3092432 TI - Comparison of isoflurane and halothane as inhalation anaesthetics in the dog. AB - A number of clinically important features of isoflurane anaesthesia were studied in comparison to those of halothane. Two groups of dogs were used. After light premedication, anaesthesia was induced by mask, and both groups of dogs were maintained for 30 minutes at 1.5 X MAC value of either halothane or isoflurane in a combination of oxygen and nitrous oxide (50:50). All animals were ventilating spontaneously. There was no difference in the speed of induction of the halothane and isoflurane groups. Blood pressure in both groups dropped to approximately 7.5 kPa (56 mm Hg) during maintenance anesthesia (1.5 MAC), while the heart rate was significantly higher in the isoflurane group. Individual respiratory variables were not significantly different between the two groups, however the differences between the trends of the mean values were significant (Sign-test). In general, with isoflurane, respiration rates were lower, with the tidal volume and end tidal CO2 being greater. The trends in pH and arterial pCO2 showed a slightly more severe respiratory acidosis in the isoflurane group. However, neither group showed values corresponding to any expected clinical problems. Speed of recovery (determined by times to head-lift and righting-reflex) was greater in the isoflurane group. Previously known important features of isoflurane are low biodegradability, low blood: gas partition coefficient, and decreased myocardial sensitivity to catecholamines. It is concluded from this study that isoflurane deserves a place in canine anesthesia whenever these specific pharmacologic properties are desired. PMID- 3092434 TI - Gametogony and sporogony of Sarcocystis fusiformis of buffaloes in the small intestine of experimentally infected cats. AB - The gametogonous and sporogonous stages of Sarcocystis fusiformis were studied in the small intestine of 10 cats each fed 350 macroscopic sarcocysts and killed 12 h, 3, 5, 7, 9, 11, 13, 15 and 17 days post infection. The macrogamonts were observed from 12 h up to 9 days post infection, whereas microgamonts were seen only on Day 3 and were very few in number. Developing oocysts were seen from Day 5 to Day 11 post infection, and from Day 13 fully sporulated oocysts and sporocysts were found in increasing numbers. PMID- 3092436 TI - [The risk strategy in pediatrics]. PMID- 3092435 TI - Treatment of Amanita mushroom poisoning: a review. AB - Poisoning with mushrooms of the genus Amanita, members of which occur frequently in both North America and Europe, accounts for a significant number of deaths annually. Liver damage is the main clinical feature and death rates are variously reported to be from 11.3% to 51.3% of patients. The amount of mushroom ingested appears to be the main prognostic indicator and a fatal outcome appears inevitable if a large amount is eaten. In sublethal exposures, supportive therapy seems effective; when definitive treatment is considered, hyperbaric oxygen, penicillin and silymarin are indicated in conjunction with careful management of blood glucose concentration. Charcoal hemoperfusion, forced diuresis, hyperbaric oxygen, and thioctic acid may also be considered, although these treatment modalities are not clearly associated with increased survival. PMID- 3092437 TI - [Education for health within medical training]. PMID- 3092438 TI - [50th anniversary of the founding of the Academy of Medicine]. PMID- 3092439 TI - [Water-electrolyte and acid-base rehydration in infants]. PMID- 3092440 TI - [Role of paramedical health personnel in the dispensary care of infants at genetic risk]. PMID- 3092441 TI - [Objectives and directions of medical care for newborn infants with intranatal disorders]. PMID- 3092442 TI - [Artificial feeding as a risk factor in infant morbidity and mortality]. PMID- 3092444 TI - [Health education in the prevention of chronic degenerative diseases]. PMID- 3092443 TI - [Neuropsychiatric emergencies]. PMID- 3092445 TI - [The Congress of the Trade Union of Dentists in Romania]. PMID- 3092446 TI - [Role of the family in socialist society]. PMID- 3092447 TI - [Active dispensary care of premature infants]. PMID- 3092448 TI - [Early detection and diagnosis of cervix uteri cancer. The role of paramedical gynecological personnel]. PMID- 3092449 TI - [The health education of workers in the machinery construction industry]. PMID- 3092451 TI - [Children and family harmony]. PMID- 3092450 TI - [Music in the service of medicine--past, present and future (I). I. From the musical bow to Orpheus' lyre]. PMID- 3092452 TI - [Protein-calorie malnutrition, a risk factor in infant morbidity and mortality]. PMID- 3092453 TI - [Myocardial infarct in the practice of the emergency service]. PMID- 3092454 TI - [Protection of children in nurseries]. PMID- 3092455 TI - [Music in the service of medicine--past, present and future. II. Music--a remedy even in the ancient world]. PMID- 3092456 TI - Morphological demonstration and quantification of TSH binding sites in neoplastic and non-neoplastic thyroid tissues. An autoradiographic study using 125I-labelled thyrotropin. AB - We have developed a morphological method to portray TSH binding sites in intact tissue specimens. Frozen sections were incubated with 125I-labelled TSH so as to localise binding sites by autoradiography. The proof of specificity was substantiated by: the competitive inhibition of 125I-TSH-labelling with cold TSH, the lack of binding in non-target tissues and a lack of binding in TSH target tissues after incubation with 125I-hCG or free 125I. In applying this method to a total of 22 surgical specimens of thyroid, striking differences came to light in respect of the degree to which 125I-TSH binding occurred in the various thyroid disorders. When compared with histologically normal tissue, labelling was generally decreased in toxic adenomas, non-functioning adenomas (cold nodules), and thyroids affected by Graves' disease, whereas non-toxic colloid goitre cases clearly exhibited denser binding. Medullary and anaplastic carcinomas exhibited no specific labelling whilst binding varied in the differentiated carcinomas between no effective binding or a level resembling that found in normal thyroid tissue. PMID- 3092457 TI - Intratumorous distribution of catecholaminergic clone cells of human neuroblastoma. A catecholamine fluorescence study. AB - The intratumorous distribution of catecholaminergic clone cells in 23 human neuroblastomas was studied using Falck-Hillarp's method, and the findings compared with the catecholamine (CA) content within the tumour. All the specimens contained elements with CA fluorescence, and the pattern of fluorescence was classified from the distribution of CA-positive cells and neurofibrils, as diffuse cellular (DC), diffuse fibrillary (DF), sporadic (S), clustered (C), island-shaped (I), and bundled (B). The strength of CA fluorescence of both cellular and fibrillary elements correlated well with the CA content within the tumour. In addition, all tumours of urinary VMA-negative cases also contained significantly larger amounts of CA than other, non-functioning, tumours in the paediatric age group. The results of this study suggest that firstly, the ratio of CA-positive cells to CA-positive neuronal processes is proportionately higher in the poorly-differentiated neuroblastomas and that secondly, even tumours negative for urinary VMA or HVA might be polyclonal and contain catecholaminergic elements. PMID- 3092458 TI - Prevention of lipofuscin development in neurons by anti-oxidants. AB - It was documented that ageing is associated with a progressive and highly significant proliferation of the total number of light microscopically visible lipofuscin granules in the grey substance of sections of the cervical spinal cord of Balb/c mice. The mean total numbers (+/- standard errors) of lipofuscin granules in standard sections of the glutaraldehyde-osmium fixed, epon embedded spinal cords that were examined with a phase contrast light microscope in 1 week, 1 month, 8 months and 18 months old mice were 0, 269 +/- 56, 1101 +/- 82 and 2464 +/- 318, respectively. The population densities of multiglobular lipofuscin units as seen with the electron microscope in random spinal cord neurons of the same 4 age groups corresponded well with the above quantitative, light microscopic data. Continuous treatment for 8 months with either the natural anti-oxidant Vitamin E (alpha-tocopherol) at 40 mg/mouse/week or the synthetic anti-oxidant butylated hydroxytoluene at about 100 mg/mouse/week diminished significantly the proliferation of lipofuscin granules in spinal cord neurons that developed during that period of ageing. No toxicity of any sort was caused by these two treatments. These results provide support for the peroxide theory of lipofuscin biogenesis and encourage further exploration of the possibilities of obtaining greater anti-lipofuscin effects with less molecular bulk of antioxidants. PMID- 3092459 TI - Three-dimensional studies of acellular glomerular basement membranes in dense deposit disease. AB - After digestion removed the cells from glomeruli of frozen kidney tissue, we employed scanning electron microscopy to examine the acellular glomerular basement membranes (AGBM) from normal kidneys and from kidneys of patients with dense-deposit disease (DDD). The AGBM showed previously unrecognized three dimensional patterns of pathologic changes. When compared to normal controls, the AGBM in DDD appeared "rigid" and thickened. Other pathologic features included coarsely granular or undulating epimembranous surfaces punctuated by single or clustered crater-like deformities. Although epimembranous crater-like deformities have been observed in other glomerulopathies, the combination of "rigid" appearing AGBM punctuated by crater-like deformities is thus far unique to DDD. PMID- 3092460 TI - Immunocytochemical demonstration of intermediate filament cytoskeleton proteins in human endocrine tissues and (neuro-) endocrine tumours. AB - The presence and distribution of intermediate filament proteins, such as cytokeratins, vimentin, neurofilament proteins and glial fibrillary acidic protein were assessed immunohistochemically in pituitary adenomas, medullary thyroid carcinomas, endocrine pancreatic tumours, gastric, intestinal and bronchial carcinoids, parathyroid adenomas, pheochromocytomas, paragangliomas and related non-neoplastic tissues. In some cases, immunohistochemical results were correlated with cytoskeletal proteins as analysed by SDS-polyacrylamide gel electrophoresis. Cytokeratin antibodies with broad range of immunoreactivity (i.e. to murine liver cytokeratin component D) reacted with epithelial cells in all non-neoplastic endocrine tissues and related neuroendocrine tumours studied, except for adrenal medulla, pheochromocytoma and paraganglioma, independently of hormone production and biological behaviour. In contrast, antibodies to epidermis derived cytokeratins failed to stain endocrine tissues and tumours. Paranuclear cytokeratin accumulations were seen in bronchial, gastric, and intestinal carcinoids and seem to be a common feature of neuroendocrine tumours. One- and two-dimensional SDS-polyacrylamide gel electrophoresis of non-neoplastic endocrine tissues and related tumours revealed two major keratin polypeptides corresponding to cytokeratins No. 8 and 18 of the cytokeratin catalog of human cells (Moll et al. 1982). According to this cytokeratin polypeptide composition, endocrine tissues and related tumours conform to the "simple type" of epithelia. Vimentin-related immunoreactivity was restricted to stromal cells and to folliculo-stellate cells in normal pituitary gland, Schwann cells in carcinoids and satellite cells in normal adrenal medulla and in pheochromocytomas. Neurofilament protein- (70 kD)-antibodies only stained nerve fibers in normal tissues and at the periphery of carcinoid tumour cell complexes, and to a variable degree, cells in nontumorous adrenal medulla, pheochromocytomas and paragangliomas. Furthermore, neurofilament reactivity was observed along with cytokeratin expression in two bronchial carcinoids. PMID- 3092462 TI - Renal vessel changes in diabetic KK-mice. AB - Glomerular hyperfiltration is thought to be of pathogenic importance in the structural abnormalities seen in diabetic nephropathy but its cause is not known. It has been suggested that the changes in the preglomerular vascular system may lead to a disturbance of glomerular blood flow in diabetes. We therefore examined the potential role of changes in the vascular system supplying the glomerulus in diabetic mice. The kidneys of 15 diabetic KK-mice (aged 2, 5 and 12 months) were studied and compared with those of 15 non-diabetic NMRI-mice. We determined vessel cross-sectional, wall and lumen areas of 408 small intrarenal arteries, 5,140 arterioles and 518 preglomerular afferent arterioles using a morphometric method. At 2 months, diabetic arteries and arterioles were considerably smaller than the controls, while preglomerular afferent arterioles were the same size. At 12 months, however, all diabetic vessels measured were much larger than the controls. This was chiefly due to an excessive increase in lumen area: in the diabetic arteries the mean (+/- SEM) lumen area at 12 months was 1,057 +/- 142 vs 616 +/- 72 sq mu in controls (P less than 0.001), in arterioles 176 +/- 7 vs 115 +/- 4 sq mu (P less than 0.001) and in preglomerular afferent arterioles (at 5 months) 131 +/- 8 vs 95 +/- 7 sq mu (P less than 0.001). The dilatation of small intrarenal arteries and arterioles in diabetic mice may result from progressive impairment of vasoconstriction and may be a cause of the glomerular hyperfiltration in diabetes. PMID- 3092461 TI - Hepatitis A-like non-A, non-B hepatitis: light and electron microscopic observations of three cases. AB - To date, three types of NANBH have been distinguished by epidemiological, clinical and experimental data. We examined the liver biopsies of three patients with an acute NANBH resembling hepatitis A from the infection route, incubation period and clinical course. The liver biopsies revealed lesions with a portal and periportal predominance, thus also exhibiting parallels with hepatitis A on the histopathological level. PMID- 3092464 TI - Heterotopic autologous splenic grafts in rat. Morphological studies. AB - Splenic grafts autotransplanted at splenectomy into the omentum of 23 Porton strain rats were compared with spleens from 10 sham-operated controls. Six months after transplantation, the grafts weighed between 81 to 545 mg (median 166 mg) compared to control spleens which weighed 775 to 1,250 mg (median 995 g). Histoquantitation of the grafts revealed marked reduction of the splenic white pulp when compared to control spleens. Morphological examination showed not only a reduction of lymphocytes but also a striking architectural abnormality in all grafts. In 2 of the transplants, no lymphoid aggregates were observed; small subcapsular collections were present in 7, while in 8, isolated perivascular aggregates of lymphocytes with poorly formed marginal zones were observed. Only 6 transplanted spleens showed linkage of adjacent lymphoid aggregates but the number and size of these aggregates were clearly less than normal. These findings indicate that autotransplanted splenic tissue in rats does not regain histological normality. The implications of these observations for autotransplantation in splenectomized patients are discussed. PMID- 3092463 TI - The cellular composition of granulomas in mesenteric lymph nodes from patients with Crohn's disease. AB - The immunohistochemical findings in granulomatous lymphadenitis in patients with Crohn's disease are presented and compared with conventional light microscopic findings. The cellular composition of the granulomas in mesenteric lymph nodes was examined with a broad panel of monoclonal and polyclonal antibodies directed to B-cells, T-cells, monocytes/macrophages, dendritic reticulum cells, HLA-DR antigens and the transferrin receptor. The centre of the granulomas contains OKIa+, OKM1+, OKT9+, DRC-, To5- epithelioid cells and giant cells and OKT3+ lymphocytes. In general, the majority of the small lymphocytes within the granulomas expresses the OKT3+, OKT4+ Leu 3a+ phenotype which points toward T helper cells. Fewer OKT3+ OKT8+ T suppressor/cytotoxic cells are observed. At the periphery of the granulomas a lymphocytic corona composed of BA1+, B1+ B lymphocytes may be present. From these findings it can be concluded that the granulomas in mesenteric lymph nodes from patients with Crohn's disease are composed of centrally located T-lymphocytes and of epithelioid cells which are of monocyte/macrophage origin and have the characteristics of antigen-presenting cells. PMID- 3092465 TI - Localization of CEA, HCG, lysozyme, alpha-1-antitrypsin, and alpha-1 antichymotrypsin in gastric cancer and prognosis. AB - Carcinoembryonic antigen (CEA), beta-human chorionic gonadotropin (HCG), alpha-1 antichymotrypsin (ACT), alpha-1-antitrypsin (AAT) and Lysozyme (LYS) were traced by immunoperoxidase staining in gastric carcinomas. The immunohistological results were evaluated in relation to histological types (WHO and Lauren), stage of disease, grade and survival time. CEA was demonstrated in 96% of the tumours, HCG in 34%, ACT in 78%, AAT in 42%, and LYS in 71%. Comparing the staining patterns of the antigens and the intensity of staining some differences were notable. Except for signet-ring cell carcinomas, all of which were intensively positive, CEA expression decreased significantly with loss of differentiation. This observation was not seen with the other marker substances. None of the tested markers was characteristic for one particular histological type, nor could they be correlated with the tumour stage or grade. The marker positivity of CEA, ACT and LYS was not related to survival time. For HCG only, a correlation between tissue expression and a restricted survival time was established. Patients with AAT positive carcinomas had a significantly better survival probability. PMID- 3092467 TI - [Lithium carbonate in the treatment of patients with diffuse toxic goiter]. PMID- 3092466 TI - A monoclonal antibody that detects myoepithelial cells in exocrine glands, basal cells in other epithelia and basal and suprabasal cells in certain hyperplastic tissues. AB - Myoepithelial and luminal cells of human exocrine glands can be positively identified with two different monoclonal antibodies. Myoepithelial cells including those of the salivary gland, mammary gland and sweat gland are positively identified by an antibody CKB1. This antibody does not stain luminal cells, but stains the basal cell layer of certain human stratified epithelia and a few basal cells in simple epithelia. Thus myoepithelial cells and basal cells have certain common features. Luminal cells can be positively stained with the CK5 monoclonal keratin antibody specific for keratin polypeptide 18; this antibody does not stain myoepithelial cells. Of interest is that CKB1 also appears to stain basal and suprabasal cells in certain hyperplastic conditions. PMID- 3092468 TI - [Anti-Pseudomonas aeruginosa activity of donor serum and the preparation "Immunoglobulin"]. PMID- 3092469 TI - [Anabolic efficacy of parenteral feeding using the amino acid preparation "Polyamine" in acute pancreatitis]. PMID- 3092470 TI - The Arizona Health Care Cost Containment System. A prepayment model for a national health service? AB - The Arizona Health Care Cost Containment System (AHCCCS), the Arizona Medicaid alternative, is an experiment in contracting "prepaid" indigent health care to the lowest bidding group. The consequences have been substantial cost overruns and serious unanswered questions about the quality and avilability of care. PMID- 3092471 TI - [Establishing recommendations for conducting serological tests for listeriosis in hospitalized women with pregnancy complications]. PMID- 3092472 TI - [A case of acute insufficiency of the peripheral arteries after short-term use of gynergen]. PMID- 3092473 TI - [Diagnosis and therapy of functional amenorrhea]. AB - Intensive research in field of gynecological endocrinology has led to various new results. For nonspecialists it seems to be difficult to draw conclusions from puzzling detail for the therapy of the patient. Today's conception of human cyclus-physiology is illustrated in this report. The various types of amenorrhoea are gathered into four functional groups. Therapy from the acting gynecologist's point of view is presented as well. PMID- 3092474 TI - Serum thyroglobulin concentration in nontoxic goiter and response to surgery with special reference to risk of goiter relapse. PMID- 3092475 TI - The metabolism of o-fluoroaniline by rats, rabbits and marmosets. AB - o-Fluoroaniline is rapidly metabolized and excreted in rats, rabbits and marmosets. Following a single oral dose of 14C-fluoroaniline of about 20 mg/kg, more than 80% of the dose is excreted in 0-24 h, the urine being the major route of excretion for all three species. For all three species, 4-amino-3-fluorophenyl is a major metabolite, conjugated at oxygen with either sulphate or glucuronic acid. 4-Acetylamino-3-fluorophenyl sulphate or glucuronide are also significant metabolites. An h.p.l.c. method with electrochemical detection was developed for monitoring exposure of plant workers to o-fluoroaniline, based on 4-amino-3 fluorophenyl sulphate. PMID- 3092476 TI - Enhancement of O-dealkylation in mouse liver by dietary administrations of BHA and BHT: studies with isolated perfused livers and hepatic microsomes. PMID- 3092478 TI - [Method for improving the diagnostic animal study in the detection of mycobacterial]. AB - In 5,400 animal tests of different specimens for detection of mycobacteria the spleen of the guinea pigs was checked for mycobacteria by microscopy and culture also after macroscopic negative results. On this way the number of positive results of animal tests could be increased by 22.6%. PMID- 3092477 TI - Impact of regional health insurance on the utilization of medical care by the rural population of Korea. PMID- 3092479 TI - [Contribution of plant and animal foods to protein intake with references for national economic efficiency]. PMID- 3092480 TI - [Adequate ventilation for health in residential buildings]. PMID- 3092482 TI - [Allogeneic heart-lung transplantation--present state and perspectives]. AB - The paper gives a survey of indication, technique, immunosuppression as well as results of the isolated heart transplantation. The isolated heart transplantation represents a genuine therapeutic alternative for many hopeless patients with heart disease who cannot be helped neither with medicamentous nor with the usual cardiosurgical methods. In future the combined heart-lung transplantation might be an essential enlargement of the treatment of patients with terminal heart diseases and with a pulmonary hypertension or of patients with a terminal pulmonary disease. PMID- 3092481 TI - [Residue dynamics of ortho-oxyquinoline in fruit and vegetables after applying kuprasal]. PMID- 3092483 TI - [Current status of allogeneic pancreas transplantation]. AB - Up to now we registered all over the world 485 transplantations of the pancreas. The partial donation of organs of relatives was performed in forty cases. On August 1st 1984 297 patients (70%) survived after a transplantation of the pancreas; of them 131 had a functioning transplant (30%). 54 transplanted organs (13%) had a good function for longer than 1 year. The most frequent complications were the thrombosis of the transplant, the pancreatitis, the fistulae of the pancreas and the rejection. Of 166 human allogenic islet transplantations at present none is functioning. Early rejections were the causes for the short function times. There were no cases of death by an islet transplantation. The present research concentrates to new methods of the islet isolation from the human pancreas and the immunological influence on the isolated islets. PMID- 3092484 TI - [Long-term pH monitoring of the esophagus. Recommendations of the Working Group on Gastrointestinal Motility for recording and evaluation using electronic data processing]. PMID- 3092485 TI - [Congenital osteoma of the skin. Attempt at diphosphonate therapy]. AB - Plaque-like congenital osteoma cutis was treated with disodium etidronate. We could not prove, however, any definitely positive effect. PMID- 3092486 TI - [Pharmacokinetics of glycerol trinitrate]. AB - The absorption, distribution and elimination of glyceryl trinitrate (GTN) in the human are extremely rapid processes. Enzymatic denitration occurs not only in the liver, but also in blood and other organs. The terminal half-life is 2-6 minutes, and clearance about 30 l/min. A large distribution volume indicates that GTN is taken up by peripheral tissues with the consequence that the concentration at the site of action is greater than in blood. The denitrated and glucuronidated metabolites make only a minor contribution to the anti-anginal effect. Within the therapeutic range there is a linear relationship between the applied dose and concentration in blood and this relationship is independent of the mode of application. GTN plasma concentration may fluctuate during prolonged infusions and transdermal application. GTN measurement on multiple plasma samples collected during the dosage interval are therefore required to obtain a reliable estimate of the steady state concentration. Individual dosage regimens are necessary to optimize therapy. PMID- 3092487 TI - [Regional ventricular function before and after sublingual administration of nitroglycerin in patients with recent myocardial infarction in the subacute and chronic stage]. AB - Seven patients with a recent myocardial infarction and mostly normal left ventricular end-diastolic pressure were investigated by radionuclide ventriculography after 3-4 days and three weeks before and after 1.6 mg nitroglycerin. Between day 3-4 and the third week global ejection fraction (EF) rose insignificantly (p greater than 0.05) from 31 +/- 4 to 37 +/- 6 percent. The regional EF in the non infarcted area remained nearly stable (74 +/- 5 to 85 +/- 13 relative percent, p greater than 0.05). However, the EF in the infarcted area rose from 22 +/- 9 to 38 +/- 11 relative percent (p less than 0.05 percent). On day 3-4 nitroglycerin induced a clear increase of the EF in the infarcted area from 22 +/- 9 to 35 +/- 11 relative percent (p less than 0.05). The global EF and the EF in the non infarcted area remained nearly constant (global EF from 31 +/- 4 to 34 +/- 5 percent, EF in the non infarcted area from 74 +/- 5 to 77 +/- 7 relative percent; p greater than 0.05). Three weeks after myocardial infarction 1.6 mg nitroglycerin did not produce a significant alteration of the ejection fraction (slight increase of the global EF from 37 +/- 6 to 40 +/- 6, the regional EF in the infarcted area from 38 +/- 11 to 48 +/- 11 relative percent and from 85 +/- 13 to 90 +/- 11 relative percent in the non infarcted area; p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092488 TI - Morphological studies on the muscle cysts of Sarcocystis dirumpens (Hoare 1933) Hafner and Matuschka 1984 in several host species revealing endopolygeny in metrocytes. AB - Muscle cysts from rodents (Mastomys natalensis, Mus musculus, Rattus norvegicus, Meriones unguiculatus, Phodopus sungorus) experimentally infected with Sarcocystis dirumpens were examined by light and electron microscopy. The corrugated primary wall showed a pattern of densely arranged invaginations surrounded by minute bleb-like evaginations. True protrusions were absent. The length of the blebs and the thickness of the primary wall varied insignificantly but not remarkable host-dependent morphological differences could be noticed between the cyst wall structures 60-418 days p.i. In the mature parts of the cysts merozoites and metrocytes showed typical apicomplexan features of fine structure and mode of multiplication (endodyogeny). In the tips of the cysts large metrocytes simultaneously formed more than two daughter cells (at least up to 12) by endopolygeny. PMID- 3092489 TI - Immunological aspects of murine infection with the rat nematode Strongyloides ratti Sandground, 1925. AB - In a study of the immune response of the rat to infection with the nematode Strongyloidis ratti, the antigens of the infective larval stage (L3) and of the parasitic, parthenogenetic female (Fp) were investigated. From both the larvae and the adult females, one metabolic (exoantigen) and two somatic antigens were extracted. Of the two somatic antigens, one was soluble and obtainable by physical means while the other was separated by chemical means from the tegument of the parasite. Humoral responses to the various antigens were evaluated by immunodiffusion and ELISA techniques, while the overall immune response was assayed by the worm burden in the immunized and subsequently infected rats. Agar gel double diffusion yielded precipitin bands only with larval somatic antigens. ELISA proved positive at a titer of 20,000 with larval metabolic antigen and sera of rats immunized against either larval metabolic or somatic antigens. By 20 days post challenge infection, however, this titer diminished to 4000. In vivo studies of worm burden in rats immunized with the various antigens and then exposed to the live L3 of the nematode showed that there were significantly fewer adult worms in the rats immunized with larval somatic antigen and adult metabolic antigen than in those immunized with adult somatic antigen or larval metabolic antigen. PMID- 3092490 TI - [Eccentric ossification of the femur head epiphysis in hip dislocation; consequences for diagnosis and therapy]. AB - Ossification of the upper femoral epiphysis is dependent on biomechanical laws. In babies with normal hips, the osseous nucleus develops in the centre of the epiphysis. In babies with hip dislocation, however, the altered biomechanical factors result in a different location of the nucleus. Ossification begins in a more lateral and cranial position. After reduction of the dislocated hip, either a second nucleus forms and grows together with the first nucleus, or the eccentric nucleus extends in a caudal direction. Both of these alternatives are physiological processes and should not be confused with necrosis of the epiphysis. The eccentric development of the nucleus is hardly mentioned in the modern literature, but it is of the greatest importance for diagnosis and therapy. Ignorance of the phenomenon of eccentric ossification may lead to a false assessment of the position of the femoral head. This mistaken impression may be heightened by an inappropriate X-ray technique: only by using techniques which take into account that the middle rotation position in children is different from that in adults can mistaken diagnoses and unnecessary operations be avoided. Examples are presented. PMID- 3092491 TI - [Treatment of progressive axial deformities in children by surgical measures of the growth plate]. AB - Report of the results of 4 surgically treated epiphyseal injuries with progressing deformities in the lower extremities (3 injuries type V, 1 epiphyseal fracture type IV according to Salter and Harris). Our Surgical procedure consisted in a resection of the posttraumatic transphyseal bony bridge with a following interposition of a silastic block to prevent again transphyseal blocking. The indications for such a surgical procedure is explained possibilities leading to failures are discussed. The results of our experimental studies being the basis for such operations are reported. PMID- 3092492 TI - [Effect of nitroglycerin on indices of hemodynamics and primary hemostasis in ischemic heart disease patients during aortocoronary shunting]. PMID- 3092493 TI - [Autolytic disintegration of the cell wall of Streptococcus group A]. PMID- 3092494 TI - [Lithium carbonate in the treatment of neurodermatitis]. PMID- 3092495 TI - [Alimentary conditioned reflex behavior in the rat following injection of 6 hydroxydopamine into the caudate nucleus and nucleus accumbens]. AB - In Wistar rats with degenerated dopaminergic terminals of the caudate and accumbens nuclei (administration of 6-hydroxydopamine, 30 mcg, bilaterally), an alimentary conditioned reflex was elaborated in a T-maze. Degeneration of the caudate nucleus terminals disturbed the elaboration, while degeneration of N. accumbens terminals did not affect the learning. PMID- 3092497 TI - Protein-energy malnutrition, iron status and malaria. PMID- 3092496 TI - [Predatory aggressiveness of the rat after intraventricular administration of individual brain-specific proteins of the S-100 group and their peptide fragments]. AB - Intraventricular injections to rats of the basic fraction of the brain specific protein S-100 in a concentration of 3 mg/ml, significantly facilitates the formation of their predatory aggression induced by the alimentary deprivation and social isolation, expressed in mice killing. This effect is not produced by fragments of S-100 molecules obtained as a result of treatment of the basic protein fraction by proteolytic enzymes. Administration of the minor S-100 fraction, albumin and rats summate brain proteins did not influence animals predatory aggression. PMID- 3092498 TI - Implications of diagnosis related groups (DRGs) for the management of hospitals. AB - Although tremendous advances have been made in the diagnosis and treatment of patients, hospital administrative systems have progressed relatively slowly. The types of information available to managers in industrial sectors are not available in the health sector. For this reason, many phenomena, such as the variations of average costs and lengths of stay between different hospitals, have remained poorly explained. The DRG system defines groups of patients that consume relatively homogeneous quantities of hospital resources. On the basis, it is possible to standardize average lengths of stay and average hospital costs in terms of the differences in case mix treated. Thus DRGs can serve as an explanation of variations in these factors between different hospitals, and also (but not only) for prospective reimbursement schemes. As in a number of other European countries, a project has been set up in Switzerland to examine the possibilities of using DRGs in hospital management, planning and financing. PMID- 3092499 TI - [Use of recombinant human gamma interferon in patients with rheumatoid arthritis]. AB - In a clinical phase II trial the efficacy and side effects of recombinant human interferon gamma in 13 patients with rheumatoid arthritis (RA) are reported. 2 patients (15.3%) showed a marked improvement of rest- and motion pains and of their general motility after a 6 and 8 month treatment. Only a temporary improvement within 2-3 months was observed in 4 patients (30.7%). In 2 cases a reduction of the erythrocyte sedimentation rate and in 4 cases a reduction of the alpha-1 acid glycoprotein and of the number of thrombocytes was documented parallel to the clinical improvement. 3 patients developed new antinuclear antibodies (ANA) or showed an increased titer of ANA. Fever was the most common side effect followed by lymphopenia and increased liver values. All side effects were reversible after dosage reduction. Our results confirm the relatively good short term efficacy of human recombinant interferon gamma in RA. In contrast, the clinical long term benefit remains doubtful. PMID- 3092501 TI - Investigations concerning the standardisation of control-investigations of supply air in air-conditioning systems in hospitals. AB - In the following investigation, air-germ measurements were conducted--using the Reuter-Centrifugal-Sampler (RCS) and the Sartorius-Sampler MD 3 (SAR), and using standardized nutrient-substratum and breeding conditions--in order to detect differences in the measuring process itself. The aim of the study was to find a standard for routine-measurements in hospitals. A special "Supply-Air-Box" was developed because of the known turbulences during the emission of air from the channel; in order to cut off the interference-factor during the measurements caused by the blending with the room-air. The results of the air-germ measurements showed a sufficient reproducability and a good representation of the results in differing measuring positions with both devices during repeated measurements. A marked difference between the two measuring-devices are the markedly higher CFU-numbers in the measurements using the RCS-device and the resulting higher variability of the single-values. The measurements using the supply-air-box show that--with the usual measuring position immediately in front of the supply-air grille screen or without grille screen at the channel end--a considerable part of room-air is also registered during the determination of the CFU-number because of the existing turbulences. Because of the markedly lower CFU numbers with this procedure, new recommendations were suggested for the maximal mean CFU-number in the supply-air. Accordingly, not more than 5 CFU/m3 of air should be found with three-step-filtered supply-air in well-maintained installations for the inrestricted utilization of the rooms, and not more than a mean value of 30 CFU/m3 of air with two-step-filtered supply-air. PMID- 3092500 TI - [Blood glucose and serum insulin levels in newborn infants of diabetic mothers during feeding with an oligosaccharide mixture]. AB - Macrosome newborns from mothers with an insulin-bound diabetes mellitus and also from mothers with a gestational diabetes show in the cord blood nearly always insulin levels additional to increased glucose values, which, compared with the normal controls are ten-fold higher in some cases. During the first three hours of life the blood glucose values decrease extremely. To prevent central injuries, caused by stronger hypoglycaemia, the early supply of oligosaccharides by continuous gastric infusion has proved as the most careful procedure. Stronger increases of blood glucose do not occur by this method and the insulin levels show a continuous tendency to normalisation. PMID- 3092502 TI - [Kinetics of germ killing and damage to selected bacterial enzymes by thermal and chemical influences. I. Theoretical background of killing and enzyme inhibition kinetics]. AB - Thermal and chemical influences on microorganisms and the kinetics of microbicidal processes are described in terms suitable to define the resistance of microbes to heat and disinfectants resp. sterilisants. Interactions between active substances (e.g. disinfectants) and enzymes are formulated in equations, and the parameters of kinetics of inactivating enzymes (e.g. Ki-values) are derived. They permit a gradual evaluation of efficacy of microbicidal agents irrespective of their concentration. PMID- 3092503 TI - [Kinetics of germ killing and damage to selected bacterial enzymes by thermal and chemical influences. II. The thermoresistance of Bacillus subtilis compared to the thermostability of enzymes of this species]. AB - The influence of moist heat on the recultivation of Bacillus subtilis-spores and on the thermal inactivation of two enzymes prepared from this species was investigated. The velocity constant k of destroying microorganisms (determination by counts of B. subtilis-spores with microbiological methods) and the specific activity (determination by biochemical methods) of creatine kinase (EC 2.7.3.2.) and aminopeptidase (EC 3.4.11.2.) were compared. A significant correlation between the logarithm of specific activity and the velocity constant (k/2,303 = 1/D) was found. A thermal exposition for 15 min and 105 degrees C was sufficient for the total inhibition of the activity of creatine kinase and aminopeptidase in the intact spores of B. subtilis. PMID- 3092504 TI - [Kinetics of germ killing and damage to selected bacterial enzymes by thermal and chemical influences. III. Damage to enzymes from Bacillus subtilis by disinfectants compared to bacterial count reduction]. AB - In the present paper a trial is reported to determine the efficacy of disinfectants by common bacteriological means as well as by biochemical methods. The results are compared, and they reveal a remarkable correlation (r = -0.9476) between the velocity constants of disinfection (1/kw) and the lg 1/Ki(app). The Ki(app)-value is the inhibition constant for the competitive inhibition of the creatine kinase reaction from Bacillus subtilis by disinfectants. The practical impacts are discussed. PMID- 3092506 TI - [The history of the Institute of Hygiene of the Medical College of Lubeck]. AB - The "Institute of Hygiene" of the Hanseatic town of Lubeck was founded in 1946 by Prof. Dr. Franz Schultz on account of the then prevailing epidemic situation mainly caused by the rapid spread of typhoid fever. The local responsibility of the Institute extended to the town itself and to the two hospitals "South" and "East", with the latter originating from the asylum of Strecknitz after its tragic destruction. In 1950 Franz Schutz was appointed ordinary professor and director of the Institute of Hygiene of the University of Gottingen. In Lubeck he was succeeded by Prof. Dr. Hans Schubert, last senior physician of the Institute of Hygiene of the University of Konigsberg. He served a very short term in Lubeck, for he died as early as 1951 after seven months' tenure. He was succeeded in office by Prof. Dr. Rudolf Preuner in 1952. During his term of office the ties with the hospitals were severed and the Institute became independent. Endeavors to found a College started in the early sixties. In November 1964 the Medical Academy of Lubeck was created as Second Medical Faculty of the University of Kiel; in 1974 it was converted into the independent Medical College of Lubeck with a presidial constitution. In 1979 Rudolf Preuner retired as professor emeritus. His successor in office was Prof. Dr. Johannes Beckert. In 1985 the College was raised to the Medical University of Lubeck. PMID- 3092505 TI - On the influence of different growth conditions to the resistance of some methylotrophic bacteria to aldehydes. AB - The resistance to formaldehyde of several facultatively methylotrophic bacteria has been investigated. The MIC-values were in the range of formaldehyde concentrations used for preservation purposes. The resistance could be explained partly by the action of aldehyde dehydrogenase found in two of the strains and by the development of a penetration barrier by the cell envelopes described formerly. PMID- 3092508 TI - [Comparison of immunity produced by B. melitensis Rev. 1 and B. abortus strain 19 in guinea pigs challenged a month nd a year after vaccination ]. PMID- 3092507 TI - [Determination of alkylation of bacterial DNA as a rapid test for toxicological evaluation of alkylating xenobiotic agents]. AB - Alkylated purine bases from hydrolized DNA can be separated by HPLC and quantified with a fluorescence detector. We applied this method to bacterial DNA. 7-methylguanine was detected after treatment of Serratia marcescens with iodoacetamide, dimethyl sulfate and with polluted air. PMID- 3092509 TI - [Biotyping of pathogenic cocci using mathematical methods]. AB - The differential information content of biological signs in the ecology of different staphylococcal and streptococcal species has been studied by the mathematical method. The method for the intraspecific differentiation of staphylococci, streptococci and gonococci into pathovars with the use of programs for the computerized analysis of the material has been proposed. The mathematical models of strain virulence in different coccal species are described. PMID- 3092510 TI - [Antigenic properties of Pseudomonas aeruginosa anatoxin and the protective action of antitoxic anti-Pseudomonas aeruginosa serum]. AB - The antigenic properties of P. aeruginosa toxoid, prepared with the use of casein culture medium, were not inferior to those of the toxoid obtained in Martin broth. In experiments on white mice antisera obtained by the immunization of rabbits with the toxoid prepared on the basis of casein culture medium showed sharply pronounced protective properties against P. aeruginosa homologous and heterologous strains, as well as toxigenic reference strain PA-103. PMID- 3092511 TI - [Dynamics of the level of antibodies to protein antigens of the Meningococcus serogroup A in the serum of patients with meningococcal infection]. AB - Two characteristics were determined in the sera of patients by means of radioimmunoassay (RIA) techniques: the RIA titer and the characteristic indicating the presence of highly avid antibodies in the serum. This investigation revealed that in the sera of patients with meningococcal infection of moderate severity the values of the RIA titer of IgM, IgG and IgA, as well as the values indicating the levels of highly avid IgM, IgG and IgA, increased as the infection progressed. In patients with the severe form of meningococcal infection the values of the RIA titer of IgA and IgA increased, while the RIA titer of IgG remained practically unchanged. No dynamic changes in the characteristics indicating the presence of highly avid antibodies in the serum were observed. PMID- 3092512 TI - [Importance of T-lymphocytes in antibody production in experimental typhus infection]. AB - The study of antibody production in cotton rats infected with Rickettsia prowazekii B and TB has revealed that R. prowazekii antigens, inducing the production of antibodies determined in the complement fixation, indirect hemolysis, and passive hemagglutination tests, are T-independent. The study of the nonspecific reactivity of T-lymphocytes in cotton rats infected with R. prowazekii TB has indicated that in case of the prolonged persistence of the infective agent in the animals no secondary immune deficiency develops. PMID- 3092513 TI - [Heterogeneity of Corynebacterium diphtheriae]. PMID- 3092514 TI - [Improved culture of Corynebacterium diphtheriae for obtaining toxin-anatoxin]. AB - The work deals with the optimization of the cultivation of C. diphtheriae with a view to obtaining diphtheria toxin--toxoid on the basis of the study of the kinetics of microbial growth and toxin formation. The combined cultivation process consisting of 3 cycles has been experimentally developed and realized under industrial conditions. The use of this cultivation method has made it possible to obtain more balanced cultures and to standardize the biological properties of the biomass and toxin thus obtained. The characteristic features of the toxoid preparations obtained on the basis of this method are a high degree of purification, good immunogenic properties and constant fractional composition; their degree of homogeneity approximates the molecular homogeneous state. PMID- 3092515 TI - [Effect of Pseudomonas aeruginosa exotoxin on blood biochemical indices in an experiment]. AB - Some problems connected with the pathogenic action of P. aeruginosa exotoxin under experimental conditions have been studied. The study has revealed that in the process of P. aeruginosa intoxication the development of hypoproteinemia, an increase in the activity of aminotransferases, lactate dehydrogenase and its isoforms occurs in the body. The characteristic features of the process are phasic changes in the activity of ceruloplasmin and in the amount of sulfhydryl groups. PMID- 3092516 TI - [Reactogenicity of a group A and C meningococcal polysaccharide bivalent vaccine]. AB - A total of 1 968 persons aged 18-20 years belonging to organized groups were immunized with different doses of polysaccharide meningococcal divaccine, groups A and C, by means of syringes and jet injectors under the conditions of a controlled epidemiological trial. Systemic reactions to the injection of the preparation were found to be absent. Local reactions manifested by inflammation, swelling and tenderness at the site of injection were faintly pronounced and disappeared in 48 hours, which is indicative of low reactogenicity of the preparation under study. PMID- 3092517 TI - [Prevention of traumatic epilepsy in ambulatory care facilities]. AB - The causes of 1382 readmissions of 156 patients with traumatic epilepsy were studied with regard to the seasonal and pathogenic factors. It was established that readmissions of patients with traumatic epilepsy directly correlated with the spring and autumn seasons and 8 pathogenic factors (no maintenance therapy, psychogenias, dysphorias, intoxication with antiepileptic drugs, alcoholization, infectious diseases and inadequate rehabilitative measures). The data obtained will help neuropathologists and psychiatrists to time repeated prophylaxis of traumatic epilepsy under outpatient conditions. PMID- 3092518 TI - [Various matters concerning the improvement of therapeutic tactics in epilepsy]. AB - The author has analyzed the results of the therapy of 200 epileptic patients and outlined the main causes of its low effectiveness: a high rate of the development and dissemination of foci of epileptic activity, a limited array of drugs for controlling non convulsive paroxysms of a complex structure, a decrease in the tolerance of large doses of drugs and intercurrent diseases. The author have developed principles of a therapeutic strategy based on the prophylactic treatment in relation to the stage and nature of the epilepsy course. PMID- 3092519 TI - [Treatment of epileptic patients with Jacksonian seizures]. AB - The article describes the treatment of patients with Jackson's epilepsy, the latter being variable in the structure and the time of development. The author offers the necessary information and recommendations concerning the characteristics of the action and pharmacokinetics of a number of antiepileptic drugs and preparations of resorptive therapy. The effect of surgery on the epileptic process is outlined. PMID- 3092520 TI - [Clinico-electroencephalographic features of patients with cerebral atherosclerosis and an epileptiform syndrome]. AB - Fifty-six patients with cerebral atherosclerosis and epileptiform symptomatology presented an organic defect with signs of lacunar imbecility and atherosclerotic asthenia. Electroencephalographic studies revealed no correlation between the clinical picture and EEG findings. Electroencephalographic parameters in patients reflect the nature of the vascular disease. PMID- 3092521 TI - Environmental change, mutational load and the advantage of sexual reproduction. AB - There is evidence that asexual reproduction has a long-term disadvantage when compared to sexual reproduction. This disadvantage is usually assumed to arise from the more efficient incorporation of advantageous mutations by sexual populations. We consider here the effect on asexual and sexual populations of changes in the fitness of harmful mutations. It is shown that the re establishment of equilibrium following environmental change is generally faster in sexual populations, and that the mutational load experienced by the sexual population can be significantly less during this period than that experienced by an asexual one. Changes in the fitness of harmful mutations may therefore impose a greater long-term disadvantage on asexual populations than those which are sexual. PMID- 3092522 TI - Self-organizing potential and morphogenetic potential (comparing current embryological and Atlan's views). AB - The concept of self-organizing potential proposed by Atlan, conceived within the framework of information theory, attempts to explain the emergence of the structures and functions of the organism, as well as the concept of morphogenetic potential, conceived in the embryological laboratories. Are the two theses diverging or converging and/or complementary to each other? The paper indicates, first, the context of Atlan's thesis and the meaning of his concepts of self organization and self-organizing potential in evolutionary systems as well as in individual systems. It then develops an in-depth analysis of these individual systems and attempts to discern, in Atlan's thesis, the respective roles of the genetic factors (first at the initial stage of the system and then in the course of its development) and of the epigenetic factors in the formation of the individual, particularly during morphogenesis. This analysis reveals some difficulties inherent in the theory and induces the author to propose a few additional distinctions. Finally, the paper underlines the analogies and divergences between the concepts of self-organizing potential and morphogenetic potential. PMID- 3092523 TI - Methodological problems in evolutionary biology. V. The import of supervenience. AB - Rosenberg has rightly argued that fitness is supervenient. But he has wrongly assumed that this makes "The fittest survive" nontautologous. Supervenience makes strict reduction impossible. It sheds light on disputes concerning the testability of evolutionary theory. PMID- 3092524 TI - Methodological problems in evolutionary biology. VI. The force of evolutionary epistemology. AB - Evolutionary epistemology takes various forms. As a philosophical discipline, it may use analogies by borrowing concepts from evolutionary biology to establish new foundations. This is not a very successful enterprise because the analogies involved are so weak that they hardly have explanatory force. It may also veil itself with the garbs of biology. Proponents of this strategy have only produced irrelevant theories by transforming epistemology's concepts beyond recognition. Sensible theories about "knowledge and biology" should presuppose that various long-standing problems concerning relations between the mental and the physical are solved. Such problems are wrongly disregarded by evolutionary epistemologists. PMID- 3092525 TI - Methodological problems in evolutionary biology. VII. The species plague. AB - Various philosophers and evolutionary biologists have recently defended the thesis that species are individuals rather than sets. A decade of debates, however, did not suffice to settle the matter. Conceptual analysis shows that many of the key terms involved ("individuation", "evolutionary species", "spatiotemporal restrictedness", "individual") are ambiguous. Current disagreements should dissolve once this is recognized. Explication of the concepts involved leads to new programs for philosophical research. It could also help biology by showing how extant controversies concerning evolution may have conceptual rather than factual roots. PMID- 3092526 TI - The regulation of metabolic clearance rate of human FSH in mice by variation of the molecular structure of the hormone. AB - The relationship between charge on human FSH (hFSH) molecules and their metabolic clearance rate (MCR) was investigated. The median charge of the hFSH molecules was expressed as their median mobility at electrophoresis in 0.075 M sodium veronal buffer, pH 8.6. MCR was estimated after single iv injection in mice of unfractionated and fractionated extracts of human pituitaries. There was a highly significant (P less than 0.001) correlation between charge and MCR both for forms of FSH present within the individual pituitary and for FSH in different pituitaries. After the iv injection there was a gradual change to a more negative median charge of hFSH in plasma. This was explained by the more rapid clearance of the less negatively charged forms of hFSH and thus selective survival of different forms in the circulation. This is a most likely explanation for the differences in median charge between FSH in pituitaries and in sera of men and women of corresponding age. The results suggest that MCR of human FSH is controlled by a gonadal-pituitary feed-back mechanism which involves changes in the structure of the FSH produced by the pituitary. It is suggested that charge is one factor involved in the regulation of the survival of FSH in the circulation and that this is of physiological importance for the control of the ovarian function during the menstrual cycle. PMID- 3092527 TI - Ontogenetic development of pancreatic thyrotropin-releasing hormone in human foetuses and in infants. AB - The ontogeny of thyrotropin-releasing hormone (TRH) in pancreata of human foetuses from 15-36 weeks of gestation and of infants has been studied. TRH was detectable in the pancreas of a 15 week old foetus; a progressive increase of pancreatic TRH content was observed until the 34th week of gestation, whereas a progressive decrease was found in the late period of pregnancy and in 1 year old infants. In contrast, the pancreatic insulin content showed a progressive increase during the entire pregnancy and in the first year after birth. These data indicate that TRH and insulin have different ontogenetic patterns in the human pancreas. PMID- 3092529 TI - Theophylline blunts the GH-response to growth hormone releasing hormone in normal subjects. AB - Theophylline enhances GH-secretion in vitro, whereas in vivo a slight decrease of basal GH-levels has been observed. In the present study the effect of theophylline on the GH-responsiveness to acute and continuous administration of growth hormone releasing hormone (GHRH) was investigated. The following protocol was performed. GHRH study. Fifty micrograms GHRH was given as an iv bolus followed by constant GHRH-infusion (100 micrograms/h) over 2 h after which another GHRH bolus of 50 micrograms was given. GHRH plus theophylline study. GHRH was administered as in the first study and theophylline was infused at a constant rate of 3.56 mg/min over 3 h, starting one h before the GHRH bolus. Theophylline study. Only saline and theophylline were infused. GHRH alone led to a GH-rise within 30 min with a maximum of 22.8 +/- 7.2 ng/ml (mean +/- SE) after which GH levels decreased despite continuous GHRH-infusion to a nadir of 12.1 +/- 4.4 ng/ml at 105 min. The second GHRH bolus led to a minimal GH-increase (13.3 +/- 6.4 ng/ml at 135 min). Theophylline administration resulted in blunting of the GH response to GHRH in all volunteers, with GH levels fluctuating between 4-6 ng/ml throughout GHRH-administration. Theophylline alone did not affect GH-levels in three subjects studied, whereas in the other one a GH secretory episode 90 min after administration of the drug was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092528 TI - Testicular plasminogen activators during postnatal development in the rat. AB - In the seminiferous epithelium, Sertoli cells secrete plasminogen activator (PA) under regulation of follicle stimulating hormone, cyclic AMP and neighbouring spermatogenic cells. Recent observations suggest that preleptotene spermatocytes upon their release from the basement membrane of the seminiferous tubule are important regulators of PA secretion. To study further the role of PA's in the seminiferous tubules, we have analyzed the endogenous levels and secretion rates of PA at various ages during postnatal development, and performed biochemical analyses of the types of PA in the testis and spent media from seminiferous tubular cultures. Cyclic secretion of PA started at the age of 28 days, and from 40 days onwards, the high secretion rates were localized in stages VII and VIII of the cycle of the seminiferous epithelium. The secreted PA is most obviously of the urokinase type; both urokinase-type and tissue-type PA-like activities were found in seminiferous tubular homogenates. The increase in testicular PA levels concomitant to the onset of meiosis in the epithelium was due to the urokinase type PA-like activity. PMID- 3092530 TI - Growth hormone releasing factor and somatomedin C production: extrahypothalamic localization and possible functional significance. AB - Growth hormone-releasing factor (GRF) is found in the highest concentration (albeit lower compared to other hypothalamic regulatory hormones) in the hypothalamus. There is mounting evidence that GRF-like immunoreactivity is found in other sites in the CNS and in the periphery. The role of GRF, other than to stimulate growth hormone secretion by the somatotroph, is unknown. In addition generation of IGF-1 in response to GRF appears to be dependent on an intact pituitary. PMID- 3092531 TI - Analysis of human myeloma cell population kinetics. AB - Pretreatment plasma cell 3H-thymidine labeling index (LI) was related to chemotherapy response in 37 multiple myeloma patients treated with alkylating agents. Response rate did not significantly differ in patients with high (greater than 3%), intermediate (2-3%) and low (less than 2%) LI values, and survival duration was significantly longer in patients with low LI irrespective of response to chemotherapy. Median response duration was distinctly shorter in patients with high and intermediate values (3 and 11 months, respectively) than in those with low values (30 months; p less than 0.01). LI at relapse was similar to that found at presentation in 5 out of 10 patients studied but was sharply increased in the other 5 who had an aggressive clinical course following initial response. Four of these latters showed a clonal evolution of bone marrow plasma cells, detected by changes in cell ploidy at flow-cytometric analysis. PMID- 3092532 TI - Glycosylated hemoglobin levels in a benign form of sickle cell anemia in Saudi Arabia. AB - Glycosylated hemoglobin was determined by the thiobarbituric acid method in sickle cell anemia patients from the Eastern Province of Saudi Arabia. The level of glycosylated hemoglobin in a Saudi SS sample (4.36%, SD 0.83) is 90% of that of the sample of normals (4.85%, SD 0.51). This is in contrast with the reported value of glycosylated hemoglobin in an American Black SS sample (3.9%, SD 0.6), which is only 60% of that of the sample of normals (6.6%, SD 0.7). The fetal hemoglobin level in Saudi sickle cell patients was 12.03% (SD 4.84), which is significantly different from that of Americans of African origin at p = 0.001. There was no significant correlation (r = 0.236) between the percentages of glycosylated Hb and Hb F at the 10% confidence level. The reported positive relationship between the percentages of glycosylated Hb and Hb F in American Blacks seems to be valid in the Saudi population only up to the level of 10-12% of fetal hemoglobin. Above this threshold of Hb F no further alleviating effect is seen. The 2,3-diphosphoglycerate value in Saudi Hb SS adults was 21.7 mumol/g (SD 7.4) and accordingly only twice as high as that of normal individuals. The benign clinical course exhibited by Saudi sickle cell patients is reflected by the survival of the RBC as indexed by its content of glycosylated Hb and 2,3 diphosphoglycerate. Moreover 10-12% of fetal hemoglobin in the RBC seems sufficient to ameliorate the severity of this disease in patients from the Eastern Province of Saudi Arabia. PMID- 3092533 TI - Ultrastructural study of blood cells in toxic oil syndrome. AB - The toxic oil syndrome is a new multisystemic disease, linked to the consumption of denatured rapeseed oil, which occurred in Spain in 1981. The hematological symptoms, present in about all the patients since the beginning of this disease have been dominated by leukocytosis and eosinophilia. The ultrastructural study of circulating blood cells has shown the presence of multiple abnormal lipid vacuoles in the eosinophil series and less frequently in neutrophils, monocytes and lymphocytes, associated to a high phagocytic activity. Bone marrow cells contrasted by the absence of lipid vacuoles in any hemopoietic series, while phagocytic activity and cytoplasmic processes were abundant. Even though patients entered the chronic phase of the disease, the hematological symptoms have spontaneously corrected themselves. PMID- 3092534 TI - Persistent cold agglutinins in AIDS and related disorders. AB - Eighty-one homosexual patients positive for HTLV-III antibody, including 19 with AIDS, 20 with chronic lymphadenopathy syndrome, 10 with AIDS-related complex (ARC) and 32 symptom-free individuals were assessed for the presence of cold agglutinins (CA). In 12 cases, CA were found; 4, 4, 2 and 2, respectively, in each of the above mentioned groups. Seven anti-I, 4 anti-i and 1 anti-Gd CA were identified. In 11 of 12 patients, CA were persistent. There were no differences between CA-negative and CA-positive patients with regard to the presence of other antibodies, anemia, frequency of intercurrent infections or development of lymphoproliferative neoplasia. It can be concluded that persistent synthesis of CA may be associated with the HTLV-III infection. PMID- 3092536 TI - Phagocytic plasma cells and Russell bodies in monoclonal gammopathy of undetermined significance. AB - Bone marrow examination in a 78-year-old woman showed a plasmacytosis with prominent erythrophagocytosis, secretory activity and numerous Russell bodies. Subsequent evaluation disclosed a monoclonal protein of IgA-kappa type and clinical and laboratory findings of monoclonal gammopathy of undetermined significance. PMID- 3092535 TI - Elliptocytosis and schistocytosis in myelodysplasia: report of two cases. AB - Marked elliptocytosis and schistocytosis are described as unusual manifestations of haematopoietic dysplasia in two patients. The first patient, whose history was negative for inherited haemolytic anaemias, presented these prominent features on his first admission; 22 months later he developed an acute myeloblastic leukaemia. In the second patient, followed since 4 years for an autoimmune thrombocytopenic purpura, elliptocytosis and schistocytosis appeared 17 months before a pancytopenia established. The patient is now on follow-up and is treated for a refractory anaemia. In both cases bone marrow examinations revealed the typical criteria for myelodysplasia and this diagnosis was confirmed by cytogenetic analysis. PMID- 3092537 TI - Hairy-cell leukaemia associated with auto-immune disorders in the form of a 'lupus-type' anticoagulant and a positive direct Coombs' test. AB - An account is given of a case of hairy-cell leukaemia associated with a 'lupus type' anticoagulant and a positive direct Coombs' test, both of which were clinically symptom free. This is yet another example of the coexistence of hairy cell leukaemia and an auto-immune disorder, but the disorder in question has not been described previously. PMID- 3092538 TI - Coincident multiple myeloma and non-Hodgkin's lymphoma with 2 serum monoclonal immunoglobulins. AB - A case with features of both multiple myeloma and non-Hodgkin's lymphoma at the moment of diagnosis is presented. The patient had lytic bone lesions and biclonal gammopathy, IgM kappa and IgA kappa. In the bone marrow biopsy, there was a diffuse infiltration by atypical plasma cells coexisting with an interstitial and nodular infiltration by poorly differentiated lymphoid cells. Immunofluorescence studies showed positive staining with alpha and kappa antisera in the cytoplasm of plasma cells and with mu and kappa antisera on the surface of lymphoid cells. After the beginning of chemotherapy, the IgA kappa monoclonal protein disappeared and the IgM kappa monoclonal protein remained constant. PMID- 3092539 TI - Subdural hemorrhage in a 32-year-old man with chronic idiopathic thrombocytopenic purpura. AB - Intracranial hemorrhage in adults with chronic idiopathic thrombocytopenic purpura is a rare but fatal complication. We report a 32-year-old patient with chronic idiopathic thrombocytopenic purpura in whom subdural hemorrhage occurred without preceding trauma and resolved following treatment with steroids and platelet transfusions. PMID- 3092540 TI - Acquired type I von Willebrand's disease in a patient with essential thrombocytosis. PMID- 3092541 TI - Immunoelectron microscopical location of the acid cysteine proteinase inhibitor in the lymphatic tissue of the tonsils. AB - Previous studies have shown the acid cysteine proteinase inhibitor (ACPI) to be a common characteristic of human squamous epithelial cells and dendritic reticulum cells (DRC) in lymphoid secondary follicles. In the present study, we used the PAP-preembedding technique for the immunoelectron microscopic identification of ACPI in DRC in palatine tonsillar tissue. ACPI appeared to be located in the cytoplasm of perikaryon and of dendritic processes of DRC on the membranes of the endoplasmic reticulum and the outer membrane of mitochondria. Further more, the tonofilaments and the desmosomal membranes exhibited a strong ACPI reactivity. PMID- 3092542 TI - Light microscopical localization of enzymes by means of cerium-based methods. I.V. Optimization procedures for acid phosphatase. AB - The earlier described cerium based histochemical reaction for acid phosphatase [Ce-Pb-reaction, Zimmermann and Halbhuber (1985)] was optimized. The target tissues (kidney, intestine) were fixed by perfusion with glutaraldehyde in cacodylate or piperazine buffer in anesthetized animals. Postfixation of prefixed sections is not advantageous because of the detectable repressing of the enzyme activity. Moreover, the employment of unfixed cryostat sections, which were postfixed, was always connected with a complete abolition of the acid phosphatase activity. The optimal concentration of the primary capture cerium III chloride in the incubation medium is about 1 mmol. Lower concentrations lead to an incomplete histochemical detection of phosphatase activity in lysosomes. The treatment of cryostat sections of perfusion fixed tissue with borohydride (diminution of aldehyde induced cross links) or with dimethylsulfoxide (extraction of lysosomal materials or the well known vehicle property) brought about an improvement of the penetration capacity for cerium-III-cations into the target structures. After conversion of the cerium phosphate (primary specific reaction product) into cerium perhydroxide, oxalate or fluoride, the Ce-Pb-reaction was negative. Therefore, these blocking reactions represent specific inhibition controls, which indicates the formation and presence of cerium phosphate. On the basis of these reactions it is possible to check the specificity of the histochemical Ce-Pb reaction for phosphatase activity in sections. PMID- 3092543 TI - Fine structure and endocytic properties of subendothelial macrophages in the bulbus arterious of two bony fish species. AB - The ultrastructure and endocytic properties of the subendothelial macrophages in the bulbus arteriosus of 2 teleosts, Cichlasoma severum and Xiphophorus helleri, are described. These cells show a diameter of 6 to 10 microns and contain a number of membrane-bound inclusion bodies, which vary greatly in size, shape, and electron density. Frequently, these bodies display myelin figures. Further, in the peripheral part of the cell there regularly occur bristle-coated vesicles. In specimens of X. helleri, injected intraperitoneally by a ferritin solution 20 to 400 h before the sacrifice, the subendothelial macrophages in the bulbus arteriosus contain large, ferritin-packed lysosomes. Similar inclusions were also seen in monocytes in the bulbar lumen. In the bulbus arteriosus of C. severum, there regularly occur mast cells beneath the endothelial lining, whereas the bulbar tissue in X. helleri lacks such cells. The present results are discussed and compared with those reported previously on the fine structure of free macrophages in mammals. PMID- 3092544 TI - Internalization and localization of membrane-associated DNA in the Tetrahymena. AB - The Tetrahymena does possess membrane-associated DNA, which binds the DNA-ase gold complex. After binding, the DNA-DNA-ase-gold complex entered the cells mainly in vacuoles delimited by unilamellar membranes, less often in coated vesicles, which released the complex near to the nucleus, to judge from appearance of gold colloid particles along the nuclear membrane and, occasionally, above the nuclear pore or, infrequently, inside the nucleus itself. PMID- 3092545 TI - Histochemical demonstration of zinc in the spermatotheka of Salamandra salamandra (L.) (Amphibia, Urodela). AB - Zinc has been localized histochemically in the spermatotheka of the salamander Salamandra salamandra using a modified dithizone method. Results are discussed regarding the specificity of the method as well as the significance of Zn for long sperm storage and for possible reactivation of spermatozoa. PMID- 3092546 TI - [Distribution of heavy metals in human ejaculate--a histochemical study]. AB - With the help of a modified dithizone method, heavy metals could be demonstrated in the sperms, the ejaculate fluid, and the spermatogenic cells of men. The heavy metals were localized in the sperms in form of small red granules particularly in the mid piece with a distribution like a "string of pearls". The sperms with a lower motility index often did not show any heavy metal granules in the mid pieces. The absence of essential heavy metals like zinc, iron or manganese may lead to the inhibition of enzyme systems in the mid pieces of the sperms, which are essential for the motility. PMID- 3092547 TI - A hemagglutination test for binding of hydrazide-derivatized cytochemical markers. AB - A sensitive hemagglutination test was developed in order to predict the ability of amine- or hydrazide-derivatized cytochemical markers to interact with cell surface aldehydes in various in vitro and in situ systems. Human red blood cells were modified by glutaraldehyde fixation and subsequent oxidation with sodium periodate, thus exposing free aldehyde residues on their surface, able to form Schiff bases with accessible hydrazide groups on the marker molecule. Fixed and oxidized erythrocytes could be stored for more than 1 year without losing their capacity to be agglutinated by polyhydrazides. The aggregating capacity of hydrazide-enriched molecules correlated well with their binding to oxidized cell surface moieties. PMID- 3092548 TI - 4-aminobutyrate: 2-oxoglutarate transaminase-containing neurons in the perinuclear zone of the rat supraoptic nucleus. AB - A pharmaco-histochemical method for demonstrating the enzyme 4-aminobutyrate: 2 oxoglutarate transaminase was applied to the sections of the rat supraoptic nucleus region. The reactions of GABAergic interneurons and their relationship to neurosecretory neurons were studied. Medium-sized neurons heavily stained for transaminase were detected in the perinuclear zone just dorsal to the supraoptic nucleus. Neurons within the supraoptic nucleus were not stained. However, the perikarya of some neurosecretory neurons in the dorsal region of the supraoptic nucleus, as well as in discrete groups scattered throughout the nucleus; were surrounded by the granular reaction products. The results strongly suggest that these strongly positive neurons in the perinuclear zone send axons to the supraoptic nucleus, where they richly divide into many branches, which synapse on the perikarya of some vasopressin and oxytocin cells. PMID- 3092549 TI - [Enzyme histochemistry of the pig placenta. III. Histotopics of enzymes in the uterine epithelium]. AB - Within the uterine glands, the following enzymes were demonstrated by histochemical methods after 30, 58, 80, 100, and 110 d of pregnancy, respectively: beta-N-acetyl-hexosaminidase, beta-galactosidase, beta glucuronidase, alpha-mannosidase, acid phosphatase, alkaline phosphatase, esterases, cytochrome oxidase, 5-nucleotidase, leucine aminopeptidase, adenosine triphosphatase, diaphorases (NADH, NADPH), glucose-6-phosphate dehydrogenase, 6 phosphogluconate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase (NAD, NADP), beta-hydroxybutyrate dehydrogenase, glycero-3-phosphate dehydrogenase, NAD-glycero-3-phosphate dehydrogenase, glutamate dehydrogenase (NAD, NADP), lactate dehydrogenase. The results show that the activities of G-6 PDH, 6-PGDH, and cytochrome oxidase increase within secreting cells during the 2nd half of pregnancy. The activities of the other enzymes remained almost unchanged during the period of investigation. The description of our results distinguishes between gland neck, middle, and distal part of the secretory unit, respectively. In general, the enzyme activities are similar within the middle and distal gland segments, but lower in the epithelia of the neck region. The activity of dehydrogenases was medium to intensive within the middle and distal gland segments, but only low to medium within the neck portion. Of the hydrolases, the acid phosphatase, ATPase, leucine aminopeptidase, and beta galactosidase demonstrated an intensive activity within activity secreting cells. The enzyme activities of the gland epithelia are compared with these of the uterine surface epithelia and the histochemical results are discussed in context with their significance in histiotrophic nutrition. PMID- 3092551 TI - Vulnerable elderly in acute care settings: a developing model. PMID- 3092550 TI - [Behavior of cysteine proteinase inhibitors in autologous epidermis transplanted into oral mucosa for relative elevation of the alveolar process]. AB - The presence of cysteine proteinase inhibitors was investigated in skin autografts into the gingiva of denture carriers. Acid cysteine proteinase inhibitors was present both in the transplant and the surrounding gingival epithelium, while neutral cysteine proteinase inhibitors was seen only in the gingival epithelium. The results indicate that the normal expression of cysteine proteinase inhibitors is conserved during the adaptation of the skin autograft into the oral surroundings. PMID- 3092553 TI - Systematic data collection: the key to behavioral assessment. PMID- 3092552 TI - Seventy years old and still vulnerable: breast self-examination is for women of all ages. PMID- 3092554 TI - The role of the public health nurse in caring for the frail elderly. PMID- 3092555 TI - Vulnerability in elderly patients in the acute-care hospital: issues in the study of power in gerontological nursing practice. PMID- 3092556 TI - Current status of clinical pancreas transplantation. AB - Pancreas transplantation (PT) has become increasingly effective for the treatment of human diabetes. Islet transplants have been successful only in the laboratory; clinical human islet transplantation needs to be improved with a search to reduce islet cells immunogenicity. Up to now, the only effective method of endocrine replacement therapy in diabetic patients is vascularized pancreas transplantation. Analysis of the International Human Pancreas Registry shows that the best options in 1985 are enteric diversion of the exocrine function, simultaneous kidney graft from the same donor and cyclosporin combined with other immunosuppressive agents in the recipient. PMID- 3092557 TI - Alteration of phage- and biotypes of Listeria strains. AB - Ethyl-methyl-sulphonate mutants of Listeria monocytogenes might be different from the parent strain in phage type and in splitting of lactose, maltose, melezitose, sucrose and trehalose. Differences were observed in repeated control studies in phage type and carbohydrate-decomposition of 550 Listeria strains isolated from a variety of sources (patients, healthy and dead animals). It has been concluded that certain carbohydrate tests are unsuitable for distinguishing biotypes of Listeria. An improvement of the evaluation of phage typing results is recommended. PMID- 3092558 TI - Metal-ion assisted detergent action on bacterial growth: detergent specificity and mechanism of inhibition. AB - Detergents in general inhibit bacterial growth. The anionic detergent, sodium lauryl sulphate (NaLS), seems to have a more specific inhibitory effect on growth of the Gram-positive Bacillus subtilis than on growth of the Gram-negative Escherichia coli. The specificity of anionic detergent towards B. subtilis has been traced to the difference in the nature of the cell wall. The inhibitory action of the detergent is markedly increased by the presence of metal ions like Cd++ or Mg++, due probably to the increase in the micellar phase, facilitating the solubilisation of bacterial species in the inner core of micelles. While metal ions like Cu++ do not influence the activity of NaLS, Na+, Ca++ or Mn++ ions seem to act against the detergent action on bacterial growth, probably by altering the structure of micelles. PMID- 3092559 TI - Immunological study of glycolipoprotein isolated from extracellular slime of different Pseudomonas aeruginosa serogroups. AB - Glycolipoprotein (GLP) was isolated by water-phenol extraction and ultracentrifugation from crude extracellular slime (C-ES) of 14 strains of Pseudomonas aeruginosa. The yields of GLP obtained between different methods were 65.6 +/- 8.4% and 46.4 +/- 11.2% of the dry weight of all C-ES fractions. GLP stimulated active immunity in mice against challenge with different immunotypes (or serogroups) of P. aeruginosa. Phenol fractions (PFr) of different P. aeruginosa strains behaved similarly. As compared to the corresponding C-ES in active mouse protection test, the GLP of several strains was less active, whereas that of some other strains was more protective. PMID- 3092560 TI - Comparison of Listeria serotypes and phage types isolated from sheep, other animals and humans. AB - A total of 814 different faecal, nasal, vaginal and milk samples of 50 healthy cotted sheep was investigated for Listeria during an epidemic-free summer season. Forty ewes and 5 tegs excreted Listeria strains; 18.1% of all samples were positive. A total of 151 Listeria monocytogenes strains belonging to serotypes 1/2, 4, 5, 6 and unknown were identified and phage typed. On the basis of the serotype and phage type of the excreted strains the animals could be divided into 7 groups. Characters of strains isolated from the cotted sheep were compared with those cultivated from 68 dead animals received from 44 distinct settlements. Also properties of 10 Listeria strains originating from 8 ill patients infected in the same region from where the carcasses of the animals were sent to the laboratory were studied. Two human Listeria strains were identical in serotype and phage type with some animal strains. PMID- 3092561 TI - Vaccination of children during treatment for leukemia. AB - Forty-one children receiving maintenance treatment for leukemia were vaccinated with inactivated mumps virus, meningococcal polysaccharide groups A and C and polyvalent pneumococcal polysaccharide vaccines. Antibodies against pneumococcal types 3, 18C, 19F and 23F and against meningococcal groups A and C were measured by radioimmunoassay. Mumps antibodies were determined by complement fixation, hemolysis-in-gel and enzyme-linked immunosorbent assays. The antibody responses tended to be lower than those of healthy age-matched controls. The individual responses were unpredictable; the magnitude of the response correlated neither with the age nor sex of the patient, duration of the chemotherapy nor with the prevaccination antibody concentration. Nevertheless, most patients achieved and even exceeded the geometric mean of the antibody concentrations of the healthy children, considered protective against infection. PMID- 3092562 TI - Prophylactic treatment with valproic acid or diazepam in children with febrile convulsions. AB - The purpose of this study was to limit prophylactic treatment of children with febrile convulsions to patients who have the highest risk of recurrence. Two hundred and thirty-one children with a first febrile seizure were divided into high- and low-risk groups according to estimated risk of recurrence. All high risk children were offered treatment with valproic acid. If this was declined they were offered treatment with diazepam instead. Low-risk children were untreated. Valproic acid and diazepam were found to be equally effective in reducing the risk of recurrence of febrile convulsions. By selecting for prophylactic treatment according to estimated risk of recurrence it is possible to reduce the rate of recurrence of febrile seizures in children at high-risk (60%) to the same level as that of untreated low-risk children (23%). Only about half of all children with febrile convulsions need treatment and follow-up according to these criteria. PMID- 3092563 TI - Study of beta-cell function and erythrocyte insulin receptors in a patient with diabetic ketoacidosis associated with L-asparaginase therapy. PMID- 3092564 TI - Severe undernutrition in Jamaica. Kwashiorkor and marasmus: the disease of the weanling. AB - The syndromes of severe undernutrition, marasmus and kwashiorkor, have causes related to the interplay of social and medical considerations in the society. Kwashiorkor supervenes when the individual is exposed to a level of stress that exceeds the body's ability to cope. One final common pathway, through which a variety of environmental factors exert an effect, may be associated with oxidant damage to cells. In kwashiorkor there is a severe decrease in the level of both oxidised and reduced glutathione in the red cell. This could be caused by a decreased production, increased consumption or a combination of the two. This is discussed with specific reference to the metabolism of glycine and the possible causal relationship to the pathophysiology of the disease process. PMID- 3092565 TI - Zinc deficiency in the weanling--how important? AB - A wide spectrum of zinc deficiency states has been recognized in the weanling. Severe zinc deficiency affects most organ systems and causes a wide variety of clinical manifestations; these occur only in special circumstances. Zinc deficiency of intermediate severity has been reported in malnourished infants, in whom it may contribute to the clinical manifestations and limit the rate of recovery from protein energy malnutrition. Results of randomized, controlled studies of dietary zinc supplementation in Denver indicate that mild nutritional zinc deficiency is one cause of failure to thrive. Better laboratory indices for the determination of mild zinc deficiency are needed before the epidemiology of this syndrome can be understood. Quantitative data on zinc absorption from different weanling diets are required before it will be possible to determine the adequacy of zinc intake. PMID- 3092566 TI - Food for the weanling: the next priority in infant nutrition. AB - The 1970s saw a revolution in the nutritional welfare of the suckling but half way through the 1980s we have yet to achieve the same success with the weanling. In the developing world the malnutrition/diarrhoea complex is a major threat to the weanling's life. Throughout the world rickets and iron deficiency are common problems. These three, protein-energy malnutrition/diarrhoea, rickets and iron deficiency anaemia are the major nutritional problems of the weanling but there are others e.g. zinc deficiency, allergy, obesity. As the weanling crosses the bridge from suckling to schoolchild he will eat the suckling's food, specially prepared weaning foods, and eventually "sensible" family foods. Beneath this bridge we need to erect a safety net of fortified foods ensuring an adequate supply of such nutrients as iron and vitamin D. PMID- 3092568 TI - Lectin-binding sites in normal, hyperplastic, adenomatous and carcinomatous human colorectal mucosa. AB - The carbohydrate structures of cellular glycoconjugates in normal, hyperplastic, adenomatous and carcinomatous human colorectal mucosa were analysed with six fluorescein isothiocyanate-conjugated lectins. In normal, hyperplastic and adenomatous colorectal mucosa showing mild or moderate dysplasia Concanavalin A (Con A), Lens culinaris (LCA), and wheat germ (WGA) agglutinins stained goblet cell glycoconjugates (actual mucin goblet itself) while peanut (PNA), Vicia villosa (VVA), and Griffonia simplicifolia-II (GSA-II) agglutinins showed a supranuclear staining of goblet cell glycoconjugates. After neuraminidase treatment of tissue sections PNA and VVA stained mucin goblets of mature cells in normal mucosa, while less differentiated cells in the lower crypt displayed a supranuclear staining with VVA. The mucin goblets in adenomatous mucosa with mild or moderate dysplasia did not stain with PNA and VVA, neither before nor after neuraminidase treatment. Areas of in situ cancer in adenomas and carcinomas displayed a strong and direct binding of Con A, LCA, WGA and PNA in an apical linear distribution, while the binding of VVA and GSA-II was heterogeneous. We conclude that there are alterations in the carbohydrate structures of cellular glycoconjugates, which can be related to goblet cell differentiation in normal colorectal mucosa and to the degree of dysplasia in adenomas. Heterogeneous and incompletely glycosylated glycoconjugates appear to be synthesized by the majority of colorectal carcinomas. PMID- 3092567 TI - Identification of inflammatory cells infiltrating renal allografts. AB - Eight nephrectomies and 13 biopsies of renal allografts (living 15, cadaveric 6) were investigated on the origin of inflammatory cells in the graft tissues by the use of an immunohistologic method (ABC method). Various monoclonal antibodies and heterosera were used to identify different leukocyte subsets. In all specimens the most predominant inflammatory cells were T cells. Other cells decreased in the following order; B cells, neutrophils and monocytes, and natural killer cells. In T cell subsets Leu 2a-positive cells (suppressor/cytotoxic T cells) predominated over Leu 3a-positive cells (helper/inducer T cells) in 4 nephrectomies (living 1, cadaveric 3) and 12 biopsies (living 11, cadaveric 1). Among these 16 cases, 7 were undergoing acute rejection in various degrees, and 9 were without clinical rejection. In the former 7 cases only one was suffering from another disease. In contrast, Leu 3a-positive cells predominated over Leu 2a positive cells in 1 biopsy (living) and 4 nephrectomies (living 2, cadaveric 2). Four of these 5 cases concurrently had other diseases in addition to acute rejection. Two cases underwent acute tubular necrosis (cadaveric graft nephrectomies) and 2 underwent chronic rejection and crescentic glomerulonephritis (living graft nephrectomies). The one remaining case was without clinical rejection. PMID- 3092569 TI - [Tabletting of a nitroglyceryl inclusion compound and testing of sustained release tablets]. PMID- 3092570 TI - Digoxin effect and imprinting in the unicellular Tetrahymena. AB - Treatment with digoxin increased, whereas treatment with ouabain decreased, the growth rate of Tetrahymena, but the progeny generations showed an increased mitotic rate after both treatments. A single exposure to digoxin or ouabain accounted for a more than twofold increase in the incorporation (binding) of the cardiac glycosides in the progeny generations. PMID- 3092571 TI - Effect of human pancreatic polypeptide (HPP) on the release of anterior pituitary hormones. AB - The effects of different doses of human pancreatic polypeptide (HPP) injected into the third ventricle was studied on plasma follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (Prl) and somatotropin (GH) in freely moving ovariectomized rats. Two hundred ng of HPP produced a significant decrease in plasma LH at 15, 30, and 60 min following microinjection. The LH-lowering effect of 400 and 800 ng of HPP developed at 5 min and persisted throughout the experiment. The strongest inhibition was observed at 15 and 30 min. No change in plasma FSH was detected at any time during the experimental period. Two hundred and 400 ng of HPP failed to influence the plasma Prl, while 800 ng resulted in a moderate but significant decrease in plasma Prl levels at 15 and 30 min following injection. Intraventricular microinjection of 400 ng of HPP decreased the GH level at 15 min and 800 ng caused a more pronounced decrease which was significant at 15, 30, and 60 min after the injection. The study suggested that HPP, either from the periphery if it can pass the blood brain barriers or produced in the brain, can influence pituitary function. PMID- 3092572 TI - Effect of haemorrhage on respiratory gas tensions in tissue fluid of the liver and the splanchnic organs. AB - In rabbits pO2, pCO2 and pH were measured in the liver and the intestinal trunk lymph as well as in arterial, portal and hepatic venous blood. In normal animals lymphatic pO2 was 40.1 +/- 2.8 mm Hg (intestinal) and 50.1 +/- 3.1 mm Hg (hepatic) respectively, and pCO2 38.0 +/- 1.0 mm Hg (intestinal) and 37.9 +/- 2.0 mm H (hepatic). In intestinal lymph representing the interstitial fluid of the splanchnic organs, pO2 did not differ significantly from the value observed in the blood of the portal vein. In the liver, pO2 was considerably higher in lymph than in hepatic venous blood. It was even higher than in the blood of the portal vein. Intestinal and hepatic pCO2 values did not differ significantly from the values in portal venous blood. The difference was significant only between liver lymph and hepatic venous blood pCO2. Acute haemorrhage by reducing arterial blood pressure to 55 mm Hg reduced markedly and in parallel lymphatic and venous pO2 without any major change in pCO2. PMID- 3092573 TI - Influence of the neonatal (clomiphene) inhibition of estradiol imprinting on gonadal development and gonadal and thyroid hormone production later in life. AB - Treatment of newborn rats with clomiphene citrate during the first 5 days of life gave rise to a marked decrease in body mass and to a still greater decrease in gonadal mass. A decrease was also observed in the testicular diameter of the males. The females showed a 43% increase in their estradiol levels over the control and an increase in the sensitivity to gonadotropins. Thyroxine level, which was also determined in view of the known gonadotropin-thyrotropin overlap, showed no change 6 weeks after pretreatment with clomiphene, while the thyroid gland responded to gonadotropin in the same manner as to thyrotropin. PMID- 3092574 TI - Effect of acidification of the duodenal contents on splanchnic circulation and metabolism. AB - Portal vein (PF) and superior mesenteric artery blood flows (SMAF), arterial and portal venous oxygen concentrations were measured in dogs before and after duodenal introduction of 3 ml/kg 0.1 mol HCl. The duodenal acidification increased PF by 30% and SMAF by 35%. The change of mesenteric oxygen utilisation, from 0.80 +/- 0.10 to 0.81 ml/kg was not significant. It is concluded that the circulatory changes after acidification of the duodenal contents are not secondary to a metabolic effect. PMID- 3092575 TI - Oxygen radical-mediated lung damage associated with alpha-naphthylthiourea. AB - Lungs were damaged with alpha-naphthylthiourea (ANTU) and various compounds were used to block its effect. Although the results are variable, superoxide dismutase, catalase and dimethylsulfoxide all protected against ANTU, indicating that OH radicals are responsible for this type of lung injury. Leukocytes do not appear to be required for the damage to occur; however, hydroxurea (given over 2 days) did block the ANTU damage when neutrophils were decreased to 1/2 normal values or when administered acutely. The free radicals may be generated by the cyclooxygenase pathway since ibuprofen blocked the ANTU damage, whereas blocking xanthine oxidase using allopurinol failed to prevent the lung damage. PMID- 3092576 TI - Carbon dioxide narcosis: influence of short-term high concentration carbon dioxide inhalation on EEG and cortical evoked responses in the rat. AB - The effects of 1 min exposure to 80% CO2 inhalation was studied in rats under light general anaesthesia with N2O. It was found that 80% CO2 gave a rapid slowing of the EEG as well as a rapid decrease of the amplitude of cortical somatosensory evoked potentials. Only minor influences upon the blood pressure and heart rate were seen. The changes were found to be transient and most of the EEG effects had disappeared about 2-3 min following the end of the CO2 exposure. The findings are related to current procedures for preslaughter anaesthesia in swine using 80% CO2. The present experiments show that 80% CO2 rapidly induces an interruption of afferent sensory transmission to the cortex as well as slowing of the EEG. Both findings indicate that 80% CO2 is an effective agent for inducing adequate anaesthesia for slaughter procedures. However, the transient nature of the CO2 effects upon the central nervous system revealed here has to be taken into account to optimize the slaughter house procedures. PMID- 3092577 TI - Increased CO2 drive for ventilation in healthy human subjects may interfere with their ability to control lung volumes voluntarily. AB - Influence of increased CO2 drive for ventilation on the ability to judge lung volume was studied in seven healthy subjects. The psychophysical relationships between the objective and subjective magnitudes of lung volume were tested during air breathing and at two levels of hypercapnia (breathing 4% and 6% CO2 in oxygen). The relationships, described by linear regression, were analysed with respect to correlation coefficient, slope and intercept of the regression line. Slope and intercept seemed to decrease as the inspired CO2 mixture increased. Statistically significant difference was found only between air and inhalation of 6% CO2 in oxygen. Correlation coefficient remained unaffected by an increase in PCO2. These results indicate that an experimental increase in PCO2 caused by 6% CO2 inhalation alters the behavioural respiratory control in healthy human subjects. PMID- 3092578 TI - Restricted diffusion of CrEDTA and cyanocobalamine across the exchange vessels in rat hindquarters. AB - The degree of diffusional restriction of skeletal muscle capillary walls to small solutes was estimated from the permeability surface area products (PS) of CrEDTA (MW = 341) and cyanocobalamine (MW = 1355), using computerized 'on-line' recordings of venous single injection indicator dilution curves. Experiments were performed on isolated perfused maximally vasodilated rat hindquarters during largely isogravimetric conditions and the arrangements allowed for measurements of capillary filtration coefficients (CFC). Extraction of tracer varied markedly as a function of transit time and, furthermore, PS increased with increasing flows, both these phenomena indicating tissue and flow heterogeneity. At maximal flows the disturbing influence of heterogeneity will be minimal and hence the diffusion capacities obtained by extrapolating PS area to infinite flows, so called PS tot values, were considered to give the best estimation of the 'true' capillary diffusion capacities. The value of PS tot was 12.9 +/- 0.5 for CrEDTA and 5.1 +/- 0.3 ml min-1 per 100 g for vitamin B12. The calculated PS tot ratio of 2.59 +/- 0.11 indicates restricted diffusion through equivalent pores of radius 53 A, whereas the ratio of the free diffusion coefficients for these solutes is 1.79. Using PS peak for the calculations (totally neglecting heterogeneity) the pore radius was, however, markedly overestimated. Thus, for a PS-ratio of 1.89 +/- 0.04 for CrEDTA vs. B12 an equivalent pore radius of 300 A was calculated. Also, using PS area (only partly correcting for heterogeneity) overestimated the pore radius (70 A) from a mean PS-ratio of 2.33 +/- 0.05. It was concluded that the equivalent pore radius in rat hindquarter microvascular walls is 53 A or even smaller in essential agreement with data from osmotic transient experiments in the same preparation (r approximately 40 A). PMID- 3092579 TI - Extracellular levels of amino acids in striatum and globus pallidus of 6 hydroxydopamine-lesioned rats measured with microdialysis. AB - Extracellular aspartate, glutamate, glutamine, taurine and GABA concentrations were measured by microdialysis in the rat striatum and globus pallidus after a unilateral 6-hydroxydopamine lesion of the dopamine system. The basal and potassium-evoked overflow of GABA was increased in the ipsilateral striatum, but the evoked overflow was decreased in both contralateral striatum and pallidum. Both basal and evoked overflow of glutamate was increased in ipsilateral striatum. The basal overflow of aspartate was significantly increased in the ipsilateral side. Basal glutamine on the other hand was decreased in the ipsilateral side. Taurine remained unchanged in both regions. These results suggest that dopamine is involved in the regulation of transmission by GABA and glutamate. Since glutamine might be the precursor to glutamate, the change in glutamate might affect the glutamine level. The changed aspartate level has no obvious explanation. PMID- 3092580 TI - The effects of lithium on neuroendocrine function in affectively ill patients. AB - Lithium is the primary treatment for manic-depressive illness. The mechanism of action of lithium and its endocrine effects remain unclear. Therefore, the hormone responses to sequential stimuli, namely arginine, TRH, and LHRH, were studied in eight patients with major depression before and during treatment with lithium. The drug was found to elevate baseline TSH and prolactin and to augment both their responses to TRH. No clinically significant effect on sex hormones was noted. The advantages of the experimental design and the implications of the findings for lithium's mechanism of action are discussed. PMID- 3092581 TI - TRH tests with analyses of TSH, prolactin, and GH responses in subtypes of patients with major depressive disorders. AB - TRH tests were performed on 131 patients with RDC diagnoses of major depressive disorders to study altered endocrine control mechanisms in subtypes of depression. The TSH response to TRH was measured in all patients. In more than a third of the sample the prolactin (PRL) and growth hormone (GH) responses were also analysed. There were no differences between bipolar, primary unipolar and secondary unipolar patients in means of any endocrine variable. However, the expected positive correlation between baseline TSH and delta TSH was absent in the secondary unipolar group, indicating a dysregulation of pituitary TRH receptor sensitivity in this depressive subtype. Only delta TSH was dependent on depressive state, being lower in currently ill primary unipolar patients only. Patients with melancholic features (endogeneity scores high) had blunted TSH responses. Weight loss was connected with TSH blunting in all depressive subtypes. Among patients with blunted delta TSH (less than 5 mU/l) there was no relationship between degree of weight loss and delta TSH. Further, examination of partial correlation coefficients suggests weight loss of affect delta TSH by virtue of its being part of the melancholic syndrome. A significant correlation between blunted delta TSH and nonsuppression of cortisol in the DST was found only among primary unipolar patients, arguing for some independence of the TRH test and the DST in mirroring disturbed endocrine controls in depression. PMID- 3092582 TI - Lithium: long-term effects on the kidney. I. Renal function in retrospect. AB - 46 patients treated with lithium for an average of 8 years participated in a functional-morphological follow-up study based on a 12-day hospitalization and involving a kidney biopsy. The functional part of the study showed that tubular function was markedly influenced, leading to increased urine volume (average 3 1/24 h) and a decreased renal concentration capacity in 85% of the patients. Glomerular function was generally not influenced, and only 10% of the patients had glomerular filtration rates below their age-corrected normal ranges. Both urine volume and glomerular filtration rates showed significant correlations with dosage schedule. Urine volume was lower and glomerular filtration rate higher on a one-dose schedule than when lithium was given in divided doses during the day. It is concluded that discontinuity in lithium treatment minimizes lithium effects on kidney function. PMID- 3092583 TI - Care of "new" long-stay patients in a district general hospital psychiatric unit. The first two years of a hospital-hostel. AB - The paper describes the need for long-term inpatient care in an English health district whose psychiatric services were based on a unit in a District General Hospital. Patients who became long-stay were placed in a new hospital-hostel in a city centre. Three quarters of those eligible could be managed in the hostel, with those rejected posing more control problems. Patients in the hostel became less withdrawn and increased their activity and use of community facilities. PMID- 3092584 TI - A comparison of DSM-III and ICD-8 diagnoses for major affective disorders and the use of biological markers for depression. AB - The aims of the present study were to investigate the value of adding DSM-III diagnosis and Newcastle Scale Rating to the ICD-8 diagnosis currently used and to investigate the association between Dexamethasone Suppression Test (DST) and the Thyrotropine Releasing Hormone- Thyroid Stimulating Hormone (TRH-TSH) test and the three classification systems for depression. Twenty-six depressed in-patients were included, 17 women and 9 men, with a mean age of 51.5 years. Fourteen patients were psychotic depressed. DST and Newcastle Scale Rating were performed on 18 patients and TRH-TSH test was performed on 16 patients. The addition of DSM III diagnosis on the 4-digit level did not have any value compared to the ICD-8 diagnosis. However, DSM-III diagnosis on the 5-digit level added important clinical information which corresponded better to Newcastle Scale scores and DST and TRH-TSH test results than ICD-8 diagnosis. The main advantage of the DSM-III classification of depression on the 5-digit level compared to ICD-8 concerns depression on the border between psychosis and neurosis. In clinical practice there is a risk of underestimating the severity of a depression if ICD-8/9 is used as the only criterion for severity. This may have tragic consequences for the patient. This study suggests that rating of the depression on the Newcastle Scale or provision of a DSM-III diagnosis on the 5-digit level are valuable assessment procedures of severity. PMID- 3092585 TI - Five years of experience with the DSM-III system in clinical work and research: some concluding remarks. AB - The reliability of the DSM-III is superior to other classification systems available in psychiatry. However, reliability depends on proper knowledge of the system. Some pitfalls reducing reliability of axis 1 diagnosis which commonly are overlooked are discussed. Secondly, some problems of validity of axis 1 and 2 are considered. This is done by discussing the differential diagnosis of organic mental disorders and other psychiatric disorders with concomittant physical dysfunction, and the diagnoses of post-traumatic stress disorders and adjustment disorders among others. The emphasis on health care seeking behaviour as a diagnostic criteria in the DSM-III system, may cause a social, racial and sexual bias in DSM-III diagnoses. The present discussion of the DSM-III system from a clinical point of view indicates the need for validation studies based on clinical experience with the DSM-III. These studies should include more out patients and patients with psychopathology who do not seek psychiatric treatment. Such studies must also apply alternative diagnostic standards like the ICD-9 and not only rely on structured psychiatric interviews constructed for DSM-III diagnoses. The discussion of axis 4 points to the problem of wanting to combine reliable rating with clinically meaningful information. It is concluded that the most important issue to be settled regarding axis 4 in the future revisions is the aim of including this axis. The discussion of axis 5 concludes that axis 5 is biased toward poor functioning and thus may be less usefull when applied on patients seen outside hospitals. Despite these problems of the DSM-III, our experiences indicate that the use of the DSM-III is fruitful both for the patient, the clinician and the researcher. Thus, the cost of time and effort needed to learn to use the DSM-III properly are small compared to the benefits achieved by using the system. PMID- 3092586 TI - Hypnotic effect of chlormethiazole in geriatric patients during long-term treatment. AB - The hypnotic effect of chlormethiazole was studied for 3 months in 20 geriatric in-patients. Registered variables were the percentage of patients asleep at 10 pm and 6 am and the observed number of awakenings. Mental and somatic variables were rated according to the Crichton Geriatric Behavioural Rating Scale. Observations were made every second week. In 11 of the patients the plasma concentration of chlormethiazole was measured at regular intervals. No systematic significant change with time was observed for the percentage of patients asleep at 10 pm or for the number of awakenings. A significant decrease occurred in the percentage of patients asleep at 6 am. The long-term treatment with chlormethiazole did not cause any deterioration in the patients' behaviour, according to the geriatric rating scheme. Observed peak plasma levels of chlormethiazole did not change significantly during the study. Great interindividual variations in the plasma concentrations were observed. The results indicate that chlormethiazole is lastingly effective as a hypnotic agent in geriatric patients. PMID- 3092587 TI - Experimental studies and clinical experiences on the dependency potential of chlormethiazole. AB - The dependency potential of chlormethiazole has been assessed on the basis of animal studies (rat and monkey) and an extensive analysis of human cases reported in the international clinical literature covering a period of 17 years. The results of the animal studies do not show any major physical or psychological dependence on chlormethiazole. Clinical studies of case reports suggest that the evidence for "primary" dependence on chlormethiazole is weak, as most of the analysable cases had a previous history of alcohol and/or other drug abuse/dependence. Moreover, in a high proportion of these cases there was evidence of simultaneous alcohol and/or other drug abuse. It should be stressed that in this group of patients the dependence on chlormethiazole was invariably reported in connection with long-term out-patient medication, that is, in a way that was not in accordance with recommendations for use of the drug in "dried out" alcoholics and/or drug addicts. Reports of chlormethiazole abuse/dependence from the alcohol/drug addiction indication are may involve a population particularly prone to addiction and, therefore, be unrepresentative for general assessment. Conversely, the findings in animal studies provide indirect support for the favourable clinical experiences with chlormethiazole in the geriatric, psychogeriatric and obstetric indication areas where chlormethiazole has been used extensively for more then a decade in a problem-free manner. The risk which applies to long-term use in alcoholics and/or drug addicts or the emotionally unstable, because of their "dependency proneness", does not seem to apply to the treatment of conditions, such as insomnia and agitation, in the elderly in whom the drug has been found to be very useful by various investigators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092588 TI - Chlormethiazole in the management of post-craniotomy seizures. AB - Epilepsy is an important problem in the period immediately following intracranial surgery. Rapid control of seizures is important to prevent damage to cerebral neuronal function. A method of managing epilepsy using intravenous chlormethiazole is reported. This regimen has proved to be safe and rapidly effective in the control of post-operative seizures. PMID- 3092590 TI - Applications of stereoselectivity of enzymes: synthesis of optically active amino acids and alpha-hydroxy acids, and stereospecific isotope-labeling of amino acids, amines and coenzymes. PMID- 3092589 TI - [Comparative study of thiotepa, adriamycin and cisplatin in the prophylaxis of recurrence of superficial bladder carcinoma in a group of 217 patients]. PMID- 3092591 TI - Genes and their organization in the replication origin region of the Bacillus subtilis chromosome: comparison with the Escherichia coli chromosome. PMID- 3092592 TI - Organization of transfer RNA genes in prokaryotes. PMID- 3092593 TI - Calcium compartmentation and regulation in myocytes. PMID- 3092594 TI - Latency of insect viruses. PMID- 3092595 TI - Causes of malabsorption in the elderly. AB - The pathogenesis of malabsorption has been studied in 70 patients who presented over the age of 65 years and who were referred to a special investigative unit. Often more than one cause was apparent. Fourteen patients had pancreatic insufficiency, most of whom had no history of pain, alcoholism or gallstones. Twenty-three patients had the postgastrectomy syndrome or small-bowel diverticulosis or both. There were eight coeliacs aged 65-72 years at diagnosis. Fifteen patients had an anatomically normal small bowel; eight of these were over 80 years old, and 10 had vitamin B12 deficiency of whom five had confirmed pernicious anaemia. Enterobacterial overgrowth was a feature of all diagnostic groups except pancreatic and coeliac disease. Vitamin B12 deficiency may be an effect of malabsorption, but can also be a cause through impairment of enterocyte function. The association of pernicious anaemia and B12 deficiency with otherwise unexplained malabsorption and bacterial overgrowth suggests that gastric atrophy is a major causal factor in this syndrome, combined in some cases with a 'vicious circle' of B12 malabsorption and deficiency. PMID- 3092596 TI - Alternative modes of action of sodium cromoglycate. PMID- 3092597 TI - Release of cytoprotective PGE2 from cultured macrophages induced by antacids and sucralfate. AB - Aluminium-containing antacids and sucralfate possess cytoprotective effects supposedly due to the release of endogenous prostaglandins. In the present study possible mechanisms of prostaglandin production by aluminium-containing and related compounds were investigated in cultured macrophages. We found no indication that mechanical action, particle size or hyperosmolality (up to certain limits) play a major role in initiating enhanced prostaglandin production. Instead, it is likely that specific physicochemical properties as surface charge and the corresponding octahedral crystalline structure of Al(OH)3 are major factors mediating the necessary membrane interactions leading to prostaglandin release. PMID- 3092598 TI - Studies on type II collagen induced arthritis in mice. AB - A consistent and reproducible polyarthritis was induced in mice by immunizing them with type II collagen in Complete Freunds adjuvant (CFA) and Bacillus Calmette-Guerin (BCG) vaccine. Several inbred strains of mice were investigated for the ability to develop collagen induced arthritis (CIA). DBA/1 mice (H-2q) produced the highest incidence and the most severe arthritis of all the strains examined. Viable BCG vaccine was essential for the induction of a reproducible disease in this strain. The effects of some anti-inflammatory and anti-rheumatic compounds were examined on the developing and established lesions of CIA. These effects were determined by assessing the paw inflammation using a subjective scoring system and measuring foot weight. Furthermore, levels of serum amyloid P component (SAP) were also determined. Benoxaprofen, cyclophosphamide, indomethacin and prednisolone inhibited the paw inflammation in the developing disease whilst the anti-rheumatic compounds auranofin and D-penicillamine exacerbate the paw inflammation. Cyclophosphamide and prednisolone inhibited the established lesions but only prednisolone prevented the development of further lesions in the established disease. The SAP levels in the prednisolone treated group were also reduced. Auranofin treatment exacerbated the inflammation of both the established and the developing lesions in the same animal. D-penicillamine was inactive in the established disease. PMID- 3092599 TI - The effects of acidic and nonacidic pyrazoles on arachidonic acid metabolism in mouse peritoneal macrophages. AB - The effects of acidic and nonacidic pyrazole derivatives and their metabolites on arachidonic acid metabolism have been investigated in mouse peritoneal macrophages stimulated with the calcium ionophore A 23 187 (10(-6) Mol/l). In the group of the acidic compounds with anti-inflammatory properties, phenylbutazone and butyl malonic acid mono (1-phenylhydrazide), the hydrolysis product of mofebutazone, inhibited prostaglandin production in a dose-dependent manner (10( 4)-10(-6) Mol/l). In contrast, mofebutazone itself and its hydroxylation product, 4-OH-mofebutazone, failed to show any activity. Similarly, in the case of bumadizone, an anti-inflammatory drug structurally related to phenylbutazone, no inhibitory effect on prostaglandin release was found either. The nonacidic pyrazole derivatives with antipyretic and anti-inflammatory activity, antipyrine, isopropylaminophenazone, as well as metamizol and its active metabolites 4 methylaminophenazone and 4-aminophenazone, also inhibited prostaglandin release dose-dependently. This was found to be paralleled by an increased leukotriene C4 production. Neither of the main excretory metabolites of metamizol, acetyl- and formylaminophenazone, showed any effect. The concentration levels at which the nonacidic compounds affected arachidonic acid metabolism (approx. 10(-4) Mol/l) were high enough to elicit anti-inflammatory effects. They were far higher, though, than the plasma levels producing antipyretic and analgesic effects that are reached after therapeutic doses. PMID- 3092600 TI - Effect of anti-inflammatory and analgesic pyrazoles on arachidonic acid metabolism in isolated heart and gastric mucosa preparations. AB - The effects of acidic and nonacidic pyrazoles on the release of arachidonic acid derived mediators from isolated perfused anaphylactic guinea pig hearts as well as rat and human gastric mucosa were investigated. High concentrations of the acidic drugs phenylbutazone and oxyphenbutazone as well as of the nonacidic metabolites of metamizol, i.e. 4-methylaminoantipyrine and 4-aminoantipyrine, inhibited the release of the cyclo-oxygenase products of arachidonic acid metabolism, TXB2 and 6-keto-PGF1 alpha, and simultaneously increased the release of LTC4-like immunoreactivity in hearts. By contrast, comparatively high concentrations of the metamizol metabolites 4-formylaminoantipyrine and 4 acetylaminoantipyrine were without effect. The comparable effects of acidic and nonacidic pyrazoles on eicosanoid release from anaphylactic hearts support the concept that hypersensitivity reactions to NSAIDs are related to their effect on arachidonic acid metabolism. The anti-inflammatory effects of phenylbutazone and oxyphenbutazone and of high concentrations of metamizol seem to be correlated with the inhibition of cyclo-oxygenase. On the other hand, lower concentrations of metamizol, which have analgesic and anti-pyretic effects, only marginally inhibit cardiac cyclo-oxygenase. It remains to be investigated whether the partial inhibition of the synthesis of PGI2, a major hyperalgesiccyclo-oxygenase product of arachidonic acid metabolism, at lower concentrations of the active metamizol metabolites contributes to the analgesic effect of metamizol. The acidic NSAID mofebutazone and its metabolite butyl malonic acid mono (1 phenylhydrazide) had no effect on the cardiac release of arachidonic acid-derived cyclo-oxygenase and lipoxygenase products. The anti-inflammatory effect of these compounds requires further investigation. In isolated gastric mucosa, the active metabolite of metamizol 4-methylaminoantipyrine was found to inhibit fatty acid cyclo-oxygenase dose-dependently. Pharmacokinetic differences due to the nonacidic structure of metamizol and its metabolites as compared to acidic NSAIDs may be responsible for the fact that metamizol is better tolerated than e.g. indomethacin. In rat experiments, phenylbutazone was found to inhibit gastric mucosal cyclo-oxygenase like indomethacin. On the other hand, mofebutazone and its metabolite butyl malonic acid mono (1-phenylhydrazide) did not affect gastric mucosal synthesis of 6-keto-PGF1 alpha. This lack of effect on gastric mucosal cyclo-oxygenase seems to be correlated with the considerably lower gastric toxicity of mofebutazone as compared to phenylbutazone. PMID- 3092601 TI - The effects of analgesics on pain-related somatosensory evoked potentials. AB - Human cerebral evoked potentials can be employed to test the effectiveness of analgesics. In the present study, pain-related cortical responses were elicited by chemical stimulation of the nasal mucosa in combination with electrical stimulation of dental pulp. In alternating sequence, 16 series of 6 chemical and 6 electrical stimuli each were presented. Interstimulus and interseries intervals were 2 s and 50-60 s, respectively. Stimulus intensities were 54% carbon dioxide (v/v) and 4 dB over the electrical current threshold of 21-45 microA for noxious chemical and electrical stimulation, respectively. Four volunteers participated in the study. The EEG was recorded at 8 sites of the international 10-20 system. After each series of stimuli, the test subjects, using visual analogue scales, rated pain intensity relative to a single standard stimulus they had received initially. After running through the procedure once, without their noticing it, the subjects intravenously received 5 ml (2.5 g) metamizol or 5 ml 0.9% NaCl, which were slowly (over a period of 12 min) added to an infusion. The entire stimulation procedure was then repeated 10 min later. Whereas the evoked potentials clearly exhibited habituation effects due to stimulus repetition within a series, the latter were absent in the subjects' pain ratings. Despite the comparatively high i.v. dose of 2.5 g metamizol, pain ratings markedly different from those given under placebo were not observed. In contrast, potential amplitudes after metamizol administration exhibited a clear tendency towards smaller amplitudes in both types of stimulation. In addition, metamizol effects on pain rating could be demonstrated successfully by applying continual chemical stimulation. PMID- 3092602 TI - [Vinculin and actin in cultured chick retinal pigment epithelial cells]. PMID- 3092603 TI - [A clinical observation on urogenital tuberculosis]. AB - A clinical observation was made on 30 cases of urogenital tuberculosis diagnosed and treated at the urological department of our Hospital between January, 1976 and December, 1984. Furthermore, 20 of them were examined for drug resistance and investigated for this tendency. They accounted for 0.23% of the outpatients. Male to female ratio was 2 to 1, but on urological tuberculosis this ratio was even. The average age was 43.7 and 50% of the patients who had a history of tuberculosis. Mycobacterium tuberculosis could be detected in 24 of the 30 cases (80%) and 18 of the 21 cases (85.4%) of urological tuberculosis. Drug resistance was examined in 20 patients. The resistant ratio of M. tuberculosis against primary drugs such as SM, PAS, INAH was low and a high resistant ratio was observed on secondary drugs such as EB, RFP, TH. These clinical observations are reported and herein discussed. PMID- 3092604 TI - Identification of Toxoplasma gondii and Encephalitozoon cuniculi by immunoperoxidase techniques and electron microscopy, in stored, formalin-fixed, paraffin-embedded tissue. PMID- 3092606 TI - One more time on DRGs. PMID- 3092605 TI - Percutaneous gastrostomy for jejunal feeding: a new technique. PMID- 3092607 TI - Serum lipids and apoproteins in students whose parents suffered prematurely from a myocardial infarction. AB - Lipids and apoproteins as well as other coronary risk factors were measured in offspring of patients who suffered from a myocardial infarction before the age of 50 years; the results are compared with the results of a control group matched for age and sex. Significant differences were observed in the apoprotein A1 level, in the protein/fat ratios of high- and low-density lipoproteins, and in smoking habits. In a multivariate analysis, the offspring group was found to be different from the control group in nonhigh-density lipoprotein cholesterol/apoprotein B ratio, high-density lipoprotein cholesterol/apoprotein A1 ratio, smoking habits, apoprotein A1, and apoprotein A2. By means of these variables a total of 85% of all subjects could be correctly classified. We conclude that as early as age 21 years the offspring of patients with premature coronary heart disease differ from matched control subjects in lipoprotein measurements and in smoking habits. PMID- 3092608 TI - Dynamics of mitral regurgitation during nitroglycerin therapy: a Doppler echocardiographic study. AB - Seven patients with decompensated chronic heart failure and functional mitral regurgitation were studied before and during administration of nitroglycerin at a mean dose of 42 micrograms/min (range 20 to 90 micrograms/min). Forward aortic flow obtained by pulsed Doppler increased significantly from 35 +/- 8 to 45 +/- 9 ml/beat (p less than 0.001) and correlated well with the cardiac output measured by thermodilution technique (r = 0.8). Whereas regurgitant mitral volume calculated from the difference between echocardiographic total stroke volume and forward aortic flow decreased significantly from 19 +/- 9 to 3 +/- 3 ml/beat (p less than 0.001), peak velocity of mitral regurgitant flow increased from 4.1 +/- 0.9 to 4.4 +/- 1.0 m/sec (p less than 0.05). The decrease in effective mitral regurgitation area derived from a modified Gorlin formula average 80%. Accordingly, in patients with decompensated chronic heart failure and functional mitral regurgitation, nitroglycerin decreases mitral regurgitant area substantially, and thus almost abolishes mitral regurgitation despite an increase in systolic pressure gradient between left ventricle and atrium. Moreover, the increase in forward flow can be entirely accounted for by the reduction in mitral regurgitant flow. PMID- 3092609 TI - Failure of nitroglycerin introduced after prolonged myocardial ischemia to improve collateral blood flow and function in tranquilized dogs. AB - This study investigated whether nitroglycerin can improve ischemic zone blood flow and function when its infusion is delayed following left anterior descending (LAD) occlusion. Nitroglycerin (200 micrograms/min, 11 dogs) or saline (six dogs) was infused for 2 hours starting 2 hours after occlusion. Regional myocardial blood flow (MBF) was measured (9 +/- 1 micron radioactive microspheres) before and at 2 and 4 hours after occlusion. Segmental contraction was determined by cineroentgenography of implanted tantalum markers. For all ischemic samples (defined as MBF less than or equal to 0.4 ml/min/gm), the average improvement in MBF in the epicardial half (EPI) was 0.05 +/- 0.02 ml/min/gm (mean +/- SEM) with nitroglycerin vs 0.06 +/- 0.06 with saline (p greater than 0.5). Improvement in the endocardial half (ENDO) averaged 0.03 +/- 0.03 ml/min/gm with nitroglycerin vs 0.09 +/- 0.08 with saline (p = 0.5). Contraction in the ischemic zone ceased following occlusion and was unaffected by nitroglycerin or saline. Control blood flows in the ischemic region were 22% less in the ENDO (p less than 0.001) and 19% less in the EPI (p less than 0.005) than in nonischemic myocardium. These results indicate that 2 hours after LAD occlusion in dogs, nitroglycerin was unable to improve ischemic zone collateral flow or contractile function compared to untreated controls. Lower ischemic zone control flows indicate that infarct volume expansion may occur within 4 hours after coronary occlusion. PMID- 3092610 TI - Increased uptake of transdermal glyceryl trinitrate during physical exercise and during high ambient temperature. AB - In a study of GTN absorption during exercise and high ambient temperature, 12 healthy volunteers carried 10 mg glyceryl trinitrate (GTN, nitroglycerin) transdermal patches for 6 hours during each of 3 days. During a control day the mean plasma GTN concentration ranged from 1.0 nmol/L (SD +/- 0.8 nmol/L) to 1.5 nmol/L (SD +/- 1.0 nmol/L), whereas during a bicycle ergometer day mean GTN concentration was increased to 3.1 nmol/L (SD +/- 1.7 nmol/L, p less than 0.001). During a sauna day volunteers stayed for 20 minutes in a sauna, and mean GTN concentration in plasma rose to 7.3 nmol/L (SD +/- 1.7 nmol/L, p less than 0.001). Systolic blood pressure increased during exercise (p less than 0.01) but decreased significantly in the sauna (p less than 0.01). Headache was noted frequently (9 of 12 subjects) and dizziness by a few (3 of 12). The demonstrated increased transdermal absorption in our study may infer an increased effect during workload. Whereas the increase in transdermally absorbed GTN may be beneficial to the exercising angina patient, increased effects of GTN may be undesirable in hot surroundings. A study on angina patients is justified to assess whether this phenomenon bears clinical relevance. PMID- 3092611 TI - Torsade de pointes: successful acute control by lidocaine and chronic control by tocainide in two patients--one each with acquired long QT and the congenital long QT syndrome. PMID- 3092612 TI - Left ventricular dyskinesia reversed by intravenous nitroglycerin: a manifestation of silent myocardial ischemia. AB - Patients with coronary artery disease (CAD) frequently have left ventricular (LV) wall motion abnormalities in the absence of symptoms. Thirty-one patients with such LV wall motion abnormalities in the absence of symptoms participated in a study of the response of these abnormalities to ascending doses of intravenous nitroglycerin (NTG). In a subgroup of 20 patients the relation between the location of LV wall motion abnormalities and the presence or absence of significant CAD (greater than or equal to 50% diameter reduction), in the vessel supplying the LV region, was assessed. Wall motion improved after intravenous NTG; the ejection fraction increased by 3.7% (mean p less than 0.05) and by 9.4% in the 19 patients who responded. There was no significant increase in heart rate; both LV systolic and end-diastolic pressures decreased minimally (12.5 and 3.5 mm Hg, respectively, p less than 0.05). The ejection fraction response was observed with NTG doses less than or equal to 200 micrograms and no dose-response relation was apparent. In the subgroup subjected to regional wall motion analysis, the presence of dyskinesia was significantly (p = 0.007) associated with the presence of important CAD in a vessel supplying that region. Further, the fact that wall motion improvement after NTG was significantly (p = 0.002) associated supports the concept that silent ischemia results in LV regional wall motion abnormalities, which can be reversed with low dose intravenous NTG. PMID- 3092613 TI - A symposium: Encainide. January 24-25, 1986, Phoenix, Arizona. PMID- 3092614 TI - Electrophysiology, hemodynamic and arrhythmia efficacy model studies on encainide. AB - Encainide is a class IC agent possessing a broad spectrum of antiarrhythmic actions in a variety of animal models. It increases the ventricular fibrillation threshold of the perfused rabbit heart and in situ dog myocardium. Encainide suppresses atrial fibrillation resulting from topical application of aconitine in the anesthetized dog and ventricular fibrillation induced by chloroform asphyxiation in the mouse. In these latter 2 models, encainide is approximately 7 to 11 and 16 to 18 times more potent, respectively, on a milligram basis than quinidine. In anesthetized dogs encainide converts ouabain-induced tachyarrhythmias to normal sinus rhythm at a mean intravenous dose of 0.67 mg/kg. Single doses of 0.5 mg/kg intravenously or 1 mg/kg orally significantly reduced ventricular ectopy in conscious dogs 18 to 22 hours after 2-stage ligation of the left coronary artery. At doses and plasma concentrations exceeding efficacious therapeutic levels, encainide has no major negative inotropic effects and does not compromise cardiac function or hemodynamics. It is devoid of peripheral autonomic or mediator-evoked responses and, in particular, lacks anticholinergic actions. Encainide is rapidly absorbed by all routes of administration and extensively metabolized by the liver. The major metabolites, O-demethyl encainide and 3-methoxy-O-demethyl encainide, have been shown to have quantitatively different, but qualitatively similar, profiles of pharmacodynamic effects. Subacute and chronic administration of encainide at doses representing 11 times an effective oral human dose have produced no distinct or consistent toxicologic findings. Carcinogenicity and mutagenicity studies were negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092615 TI - Dosing recommendations for encainide. AB - The onset of antiarrhythmic action of encainide in patients with ventricular arrhythmias occurred within 3 hours after a single dose of 25 or 50 mg. No significant antiarrhythmic activity was noted after only 10 mg. After 14 days of daily dosing, both the 25- and 50-mg dose levels of encainide administered 3 times/day abolished or decreased ventricular arrhythmias in patients tested over a 24-hour period, whereas the 10-mg dose was ineffective. In 5 well-controlled studies involving 331 patients, encainide produced a dose-related decrease in the absolute number of ventricular arrhythmias as well as an increase in the percentage of responders (greater than 75% decrease in ventricular arrhythmias). Doses of 75 mg/day were required to obtain at least a 50% reduction in ventricular arrhythmias or 50% of patients responding or both. Three-times-a-day dosing was as effective as 4-times-a-day dosing. Further, doses greater than 200 mg/day gave little or no increase in incidence of efficacy. Important side effects were very low using doses of less than or equal to 150 mg/day and increased significantly at greater than or equal to 150 mg/day. It is recommended that encainide be initiated at 25 mg 3 times/day for 4 to 7 days, then carefully titrated upward, as needed, to 35 and 50 mg 3 times/day, respectively, every 4 to 7 days. If needed, 50 mg 4 times/day is an appropriate next dosage. Rapid dose escalation or doses greater than 200 mg are discouraged. Patients with severe life-threatening arrhythmias should receive encainide in a setting with cardiac monitoring and advanced life support systems. PMID- 3092616 TI - Acute intravenous and long-term oral hemodynamic effects of encainide. AB - The short- and long-term hemodynamic effects of encainide, a new class IC antiarrhythmic agent, were studied in 25 patients (mean age 61 +/- 11) with complex symptomatic ventricular arrhythmia and left ventricular dysfunction. Ninety-two percent had previous myocardial infarction and 8% had dilated cardiomyopathy. Seventy-five percent had congestive heart failure, class III or IV, according to the New York Heart Association. All patients underwent a nuclear ventriculogram performed at least 3 days after discontinuing previous antiarrhythmic drugs. Nuclear ventriculograms were repeated 1 to 6 weeks later while the patients were receiving therapeutic doses of encainide ranging from 75 to 300 [corrected] mg/day. Nuclear ventriculograms were also repeated after 6 months or 1 year of encainide therapy in 16 of these patients. Encainide did not have significant effects on heart rate, blood pressure, left ventricular ejection fraction, systolic or end-diastolic volumes. None of the patients showed a worsening of congestive heart failure during encainide therapy. These results compare favorably with those of other class I antiarrhythmic agents. A review of published reports on the hemodynamic effects of intravenous encainide shows it to have a mild but statistically significant dose-related depressant effect on cardiac function. This effect, however, appears to be no different from that of other newer class I agents. PMID- 3092617 TI - Electrophysiology in assessing supraventricular arrhythmias: value of programmed stimulation in predicting and understanding efficacy of encainide. AB - The effects of intravenous (1.5 mg/kg body weight given over 15 minutes) and oral (mean dose 164.8 +/- 56.2 mg/day) encainide were studied in 11 patients with recurrent, difficult to treat, supraventricular tachycardia. In 2 patients the arrhythmia was atrial in origin. In 9 patients a concealed (slow type in 3, fast type in 6) accessory atrioventricular pathway was used for retrograde conduction during a circus movement tachycardia. Intravenous encainide terminated tachycardia in 8 of the 11 patients. Oral encainide prevented clinical recurrence of tachycardia in 7 patients during a 5- to 20-month follow-up (mean 11). Programmed stimulation of the heart after intravenous encainide administration revealed significant (p less than 0.05) prolongation of HV interval, QRS width and refractory period of the right ventricle. Apart from a slower tachycardia rate no changes in electrophysiologic parameters were observed in 5 patients restudied while receiving oral encainide medication. Although encainide was an effective antiarrhythmic agent, programmed stimulation of the heart was not very helpful in providing insight into its mode of action, nor did programmed stimulation predict clinical efficacy. Prevention of the tachycardia-initiating premature beat seems to be the most likely mechanism for the clinical efficacy of oral encainide. PMID- 3092618 TI - Disposition kinetics of encainide and metabolites. AB - Interpretation of plasma concentration data during encainide therapy is predicated on an understanding of the role of active metabolites during treatment. In over 90% of patients, encainide is rapidly biotransformed to O desmethyl encainide (ODE) and 3-methoxy-O-desmethyl encainide (3-MODE), which persist in plasma hours after encainide itself is undetectable. This metabolism occurs in the liver, and encainide clearance is sufficiently high that a significant first-pass effect is seen during oral therapy (bioavailability 30 +/- 7%). In these extensive metabolizers, ODE and 3-MODE appear to mediate the arrhythmia suppression and electrocardiographic changes seen during encainide therapy. In less than 10% of patients, a genetic defect prevents expression of the enzyme responsible for the rapid biotransformation of encainide. In this poor metabolizer subset, the systemic clearance of encainide is 10-fold lower than in extensive metabolizers (0.18 +/- .002 vs 1.9 +/- 0.2 liters/min), the first-pass effect is virtually absent (bioavailability 83% to 88%), plasma concentrations are higher and an antiarrhythmic effect may be seen at usual encainide doses. Minimally effective plasma concentrations appear to be 35 ng/ml (ODE), 100 ng/ml (3-MODE) and 300 ng/ml (encainide), making ODE one of the most potent sodium channel blockers yet used in man. The elimination half-life of encainide is 2.3 +/- 0.3 hours in extensive metabolizer patients. Despite this rapid elimination, encainide can be administered every 8 to 12 hours in both extensive and poor metabolizer subsets; this is because of slowly eliminated metabolites in extensive metabolizers and slower elimination of encainide itself (11.3 +/- 0.3 hours) in poor metabolizers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092620 TI - Encainide for refractory supraventricular tachycardia in children. AB - Fifteen children, aged 5 days to 19 years (mean 4.7 years), with medically refractory supraventricular tachycardia were given oral encainide. In 10 of 15 children with "incessant" tachycardia (greater than 10% of the day), encainide alone controlled supraventricular tachycardia in 5 children; in combination with other antiarrhythmic agents, it partially controlled supraventricular tachycardia in 4 and was ineffective in 1. In 5 children with accessory atrioventricular connections, encainide eliminated supraventricular tachycardia in 3 and was ineffective in 2. Therapeutic encainide dosages ranged from 60 to 120 mg/m2/day (mean 90) (2.0 to 5.7 mg/kg/day). Encainide caused prolongation of the PR interval by 35%, RP interval by 17%, QRS interval by 44% and corrected QT interval by 10%. In 5 children with depressed left ventricular function administration of encainide, by controlling the arrhythmia, increased echocardiographic left ventricular shortening fraction from a mean of 24% to a mean of 36%. Three patients developed excessive QRS aberrancy, which was associated with wide QRS tachycardia in 2. No adverse reactions were noted in the absence of QRS aberration. Side effects were minor and noted in only 1 of 9 patients continuing to take the drug in 9 months of follow-up. Encainide was effective, or partially effective, in the control of resistant or incessant supraventricular tachycardia in 80% of children treated. Encainide allowed rapid resolution of arrhythmia-induced cardiomyopathy by controlling chronic supraventricular tachycardia. PMID- 3092619 TI - Encainide for treatment of supraventricular tachycardias associated with the Wolff-Parkinson-White syndrome. AB - Thirty-three patients with supraventricular tachycardia associated with the Wolff Parkinson-White syndrome were treated with encainide for 26 months (mean). Encainide at a mean dosage of 187 mg/day abolished or markedly decreased episodes of palpitations in 24 of 33 (73%), and no patient had syncope or required cardioversion while receiving the drug. Encainide was well tolerated and was discontinued in only 2 patients because of side effects (6%). Only 1 patient (3%) had a proarrhythmic effect while taking encainide (ventricular tachycardia). Fourteen of 16 patients (88%) with atrial fibrillation continue receiving encainide. Episodes of palpitations have been abolished or markedly decreased and no patient has had syncope or required cardioversion. All 14 of these patients had either anterograde block in the accessory pathway during atrial fibrillation or greater than or equal to 75 ms increase in the shortest R to R interval formed by 2 preexcited QRS complexes. Encainide prolonged refractory periods of the atrial (p = 0.064) and ventricular (p = 0.061) muscle. It prolonged the cycle length at which 1:1 conduction of the accessory pathway in both the anterograde and retrograde directions occurred (both, p less than 0.001). Induction of atrioventricular-reciprocating tachycardia (AVRT) was prevented in 36% of patients at repeat electrophysiologic study. The AVRT cycle length increased 112 ms (mean, p less than 0.001) in those patients in whom AVRT was still inducible. The loss of delta waves recorded with the 12-lead scalar electrocardiogram during encainide therapy was a significant predictor of anterograde accessory pathway block (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092621 TI - Treatment of supraventricular arrhythmias with encainide. AB - Encainide has been used to treat 230 patients with supraventricular arrhythmias, including patients with reentry supraventricular tachycardia of the atrioventricular reentry (Wolff-Parkinson-White syndrome) and the atrioventricular nodal reentry types associated with atrial fibrillation, paroxysmal supraventricular tachycardia or both, as well as incessant supraventricular tachycardia. The available data are summarized in this review. The short- and long-term response to encainide for preventing recurrence or lessening symptoms was excellent in most cases. There was little arrhythmia aggravation, and side effects, which were mostly central nervous system and visual in nature, did not cause discontinuation of the drug. Anterograde accessory pathway block was clearly an important effect. Whether retrograde block or refractoriness in the accessory pathway is the most important mechanism remains to be resolved. Pediatric patients with tachycardia-related cardiomyopathy responded well to encainide. Oral encainide's absence of effect on blood pressure or myocardial contractility is an added benefit. PMID- 3092622 TI - Relation of blood level and metabolites to the antiarrhythmic effectiveness of encainide. AB - Encainide is a potent new antiarrhythmic agent with 2 major active metabolites and 2 distinct phenotypes for metabolism, extensive (approximately 92%) and nonextensive (8%). Encainide is an active compound with close correlation of plasma levels with antiarrhythmic effectiveness and electrocardiographic changes in nonextensive metabolizers. Its metabolites, O-demethyl-encainide and 3-methoxy O-demethyl-encainide, are active against experimental and clinical arrhythmias. They have longer half-lives than and equal or greater potency than the parent compound. All 3 compounds contribute to the antiarrhythmic profile in extensive metabolizers. There is no readily apparent relation between encainide and its metabolites, blood levels and efficacy because of the complexity of the 3 active compounds and individual variation in pharmacokinetic and arrhythmia responsiveness. Encainide has been given for up to 2 years in 140 patients with sustained ventricular tachycardia or ventricular fibrillation. The survival curves are similar to historical control data from patients reported by Graboys and Swerdlow. The survival curves for long-term administration in patients with frequent ventricular premature complexes (greater than 30/min) are comparable to data from Califf. While these data must be viewed cautiously, it seems fair to conclude that encainide is as effective as any combination of drugs for preventing sudden death in patients with life-threatening ventricular arrhythmias. PMID- 3092623 TI - Encainide for ventricular arrhythmias: placebo-controlled and standard comparison trials. AB - Efficacy data obtained from the use of encainide in the treatment of patients with benign or potentially lethal ventricular arrhythmias are reviewed. These include an oral dose multicenter titration study involving 111 patients in whom encainide was given from 25 to 75 mg, 4 times/day, which was followed by a 3 center, reduced dose study in which 35 patients received a forced escalation of encainide from 10 to 30 mg, 4 times/day. Frequent Holter monitoring was used to judge efficacy. An 8-center, double-blind, parallel, placebo-controlled outpatient trial was conducted using encainide from 10 to 50 mg, 3 times/day, in 125 patients. This trial defined the lower end of the dose response curve for encainide to be 25 mg, 3 times/day. The data from all these trials show that when properly titrated, encainide is effective in decreasing ventricular premature complex frequency by at least 75% in about 80% of patients. A similar percentage will have abolition of ventricular tachycardia. When encainide was compared with quinidine in a 9-center placebo-controlled crossover study, encainide demonstrated more efficacy at 25 mg, 4 times/day, compared with quinidine at 200 mg, 4 times/day, in all arrhythmia parameters. Encainide was also better tolerated than quinidine and there was no statistically significant difference in the prevalence of asymptomatic proarrhythmia as detected by Holter monitoring between these 2 drugs. Long-term data in 220 patients over 36-month follow-up show continued encainide efficacy. Thus, encainide is a potent, effective class 1C antiarrhythmic agent and it has minimal negative inotropic effects and is well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092624 TI - Encainide in lethal ventricular arrhythmias evaluated by electrophysiologic testing and decrease in symptoms. AB - Encainide hydrochloride has distinct electrophysiologic properties that suggest active antiarrhythmic properties. Encainide has been administered both intravenously (0.5 to 1.7 mg/kg) and orally (100 to 300 mg/day) to patients with lethal ventricular arrhythmias--ventricular tachycardia (VT) and ventricular fibrillation--and evaluated by electrophysiologic testing. In 62 patients with inducible sustained VT, intravenous encainide prevented initiation in 13 (21%). In 57 patients with refractory sustained VT, oral encainide prevented initiation of VT by programmed stimulation in 17 (30%). The results obtained with intravenous and oral encainide in the same patient were usually concordant (93%). Encainide may worsen ventricular arrhythmia, most typically by converting nonsustained VT into sustained VT during electrophysiologic testing. In patients with lethal ventricular arrhythmia, analysis of symptoms before and during chronic encainide therapy showed that the number and severity of arrhythmia related symptoms were reduced. Encainide appears to be a useful antiarrhythmic agent. PMID- 3092625 TI - Safety and efficacy of encainide for malignant ventricular arrhythmias. AB - The antiarrhythmic effect of encainide was evaluated in 140 patients with documented symptomatic ventricular tachycardia or ventricular fibrillation refractory to conventional agents. In 102 patients with reproducible spontaneous arrhythmia, noninvasive methods, including ambulatory monitoring and exercise testing, were used to evaluate drug efficacy, while in the remaining 38 patients electrophysiologic testing was performed. Side effects necessitated drug discontinuation in 10 patients before noninvasive evaluation. Of the remaining 92 patients 44 (48%) responded to encainide. Of the 38 patients who underwent electrophysiologic study, 1 discontinued encainide because of side effects and in 4 patients the spontaneous occurrence of sustained ventricular tachycardia precluded repeat study. Of the remaining 33 patients, 10 (30%) were rendered noninducible with encainide. The drug was more effective in those with a left ventricular ejection fraction greater than 35% (p less than 0.03) and in those presenting with nonsustained ventricular tachycardia. Side effects were reported in 53 of 140 patients (38%) and were primarily nausea, vomiting, headaches and tremors. Aggravation of arrhythmia occurred in 4% of patients with a history of nonsustained arrhythmia and in 25% of those with a history of sustained ventricular tachycardia or ventricular fibrillation. Worsening of arrhythmia was not related to mean dose of drug, mean blood level or electrocardiographic changes; it was more likely to occur in patients with a markedly reduced left ventricular ejection fraction (average 32%) and in those with a history of sustained ventricular tachyarrhythmia (p less than 0.05). Long-term encainide therapy was continued in 48 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092626 TI - Safety of encainide for the treatment of ventricular arrhythmias. AB - A data base of 1,245 patients treated for ventricular arrhythmias, most of whom had serious cardiac disease, was reviewed. Only 2.9% of these patients had benign ventricular arrhythmias without structural heart disease. The overall incidence of proarrhythmia in this population was 9.2% (115/1,245), but was as frequent as 16% in patients with a history of cardiomyopathy. The proarrhythmic form was new sustained ventricular tachycardia in 22 patients (1.8%). Only 2 of 71 patients (2.8%) with primary arrhythmia had a proarrhythmic event. The incidence has decreased markedly over the past years as reduced doses and gradual titration have been used. There were 137 deaths in the data base of which 82 were sudden, all in patients with advanced (79) or moderately severe (3) cardiac disease. High initial doses, prior myocardial infarction and congestive heart failure (CHF) were positively associated with sudden cardiac death. There were no deaths among the 71 patients with benign arrhythmias. Death rates were related to the severity of the arrhythmia being treated. Comparisons with published survival curves indicated modest improvement; in no case was survival decreased. Invasive and noninvasive measures of left ventricular function indicated no adverse hemodynamic effects. There was only 1 case of new and 3 cases of worsened CHF probably related to encainide. Only 5 patients discontinued for CHF or related signs and symptoms. The most frequent drug-related noncardiac adverse reactions were dizziness (26%), abnormal or blurred vision (19%), QRS interval prolongation (5%), taste perversion (4%) and tremor (3%). In conclusion, the use of reduced doses and gradual titration of encainide has markedly decreased the incidence of proarrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092627 TI - Alterations in regional myocardial blood flow after nitroprusside and nitroglycerin in patients with and without significant coronary artery disease. AB - To evaluate vasodilator-induced redistribution of regional myocardial blood flow, intravenous sodium nitroprusside and nitroglycerin were administered in doses producing matched reductions (15%) in mean arterial pressure at constant heart rate. Anterior left ventricular great cardiac vein blood flow (thermodilution) was measured in 14 patients without angiographic anterior collateral supply. Global coronary sinus blood flow remained constant with both nitroprusside and nitroglycerin administration, despite significant reductions in mean arterial pressure. However, nitroglycerin reduced great vein flow by 25 +/- 17% and nitroprusside by 10 +/- 16% (p less than 0.01). Subgroup analysis indicated that the nitroglycerin-nitroprusside regional blood flow differences were more pronounced in patients without significant left anterior descending coronary artery narrowing. Neither vasodilator produced significant differences in arterial-coronary sinus oxygen or lactate contents, calculated myocardial oxygen consumption, left ventricular dP/dt, or electrocardiographic or clinical signs of myocardial ischemia. Despite qualitatively similar hemodynamic effects, comparisons of vasodilator-induced relative reductions in normally supplied anterior left ventricular regional coronary blood flow suggest a mechanism of the reported beneficial effects of nitroglycerin on potentially ischemic myocardial regions. PMID- 3092628 TI - Effects of bepridil on regional myocardial ischemia and comparison with verapamil. AB - This study was designed to assess the efficacy of bepridil in reducing regional myocardial ischemia and to compare its efficacy with that of verapamil. Forty five anesthetized, open-chest dogs were subjected to three 5-minute occlusions of the left anterior descending coronary artery (LAD), each followed by 45 minutes of reperfusion. Eleven dogs (group 1) served as controls. In 10 dogs, bepridil, 5 mg/kg, was administered before the third occlusion (group 2). In 11 dogs, verapamil was administered before the third occlusion (group 3). In each dog, on line intramyocardial hydrogen ion concentration and carbon dioxide tension were measured in the myocardial segment supplied by the LAD. Regional myocardial contractility was assessed in this area with 2 pairs of ultrasonic crystals inserted to determine percent segmental shortening. Regional myocardial blood flow was determined during each occlusion by washout of xenon-127. The increase in hydrogen ion concentration and carbon dioxide tension did not change from occlusion 2 to occlusion 3 in the control group. Both bepridil and verapamil elicited a significant reduction in the extent of regional ischemia, evidenced by a reduction in the accumulation of hydrogen ions, in occlusion 3 vs occlusion 2. Systolic bulging occurred during all occlusions and the periods of reperfusion were not sufficient to allow complete recovery of regional function. Bepridil and verapamil each caused a significant increase in percent segmental shortening (both p less than 0.025), and verapamil effected a significant improvement of function during occlusion 3 compared with occlusion 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092629 TI - Comparison of the doubly labeled water (2H2(18)O) method with indirect calorimetry and a nutrient-balance study for simultaneous determination of energy expenditure, water intake, and metabolizable energy intake in preterm infants. AB - The doubly labeled water method was compared with indirect calorimetry and a nutrient-balance study for simultaneous determination of rates of CO2 production, energy expenditure, and water intake over 5 days in four preterm infants. Additionally, metabolizable energy (ME) intake estimated using the isotope procedure (as energy expenditure plus an estimate for energy deposition based on weight gain), was compared to ME intake measured in the balance study. Compared to values obtained by traditional methods, calculated CO2 production, energy expenditure, and water intake differed by -1.4 +/- 4.8% (SD), +0.3 +/- 2.6%, and +5.7 +/- 1.4%, respectively; the difference in water intake was significant (p less than 0.05). Calculated ME intakes were 5.3 +/- 19.3% less than measured intakes, but the difference was not significant. These findings indicate that the doubly labeled water method can provide accurate information on rates of CO2 production, energy expenditure, and water intake in preterm infants, but individual estimates of ME intake may be subject to substantial error. PMID- 3092630 TI - Energy expenditure in chronic alcoholics with and without liver disease. AB - Chronic alcoholism activates metabolic pathways, resulting in wasteful expenditure of energy (Pirola and Lieber, J Nutr 1975;105:1544-8). To study this hypothesis, we measured oxygen consumption (VO2), carbon dioxide production (VCO2), and resting energy expenditure (MREE) utilizing indirect calorimetry in 8 chronic alcoholics with (group I) and 11 chronic alcoholics without (group II) clinical or biochemical evidence of alcoholic liver disease. Seven healthy volunteers served as controls. A statistically increased MREE was observed in group II subjects (p less than 0.05, MREE 999.7 +/- 111.4 kcal X day X m2) as compared to normals (MREE 842.3 +/- 42.1 kcal X day X m2) and group I subjects (MREE 813.4 +/- 101.4 kcal X day X m2). VO2 and VCO2 were also significantly higher (p less than 0.05) in group II than in group I and normals. The predicted resting energy expenditure as calculated by the Harris-Benedict equation was similar in both groups and normals. Theories to explain the increased MREE in group II subjects are presented. PMID- 3092631 TI - Taurine concentrations in plasma and blood cells of patients undergoing long-term parenteral nutrition. AB - Taurine concentrations were measured in plasma and blood cells of 40 adults undergoing long-term parenteral nutrition, without intravenous taurine, for 43.8 +/- 35.1 (SD) mo. Patients were classified into Group 1 (21 patients) or Group 2 (19 patients) according to whether their estimated enteral absorption of calories was less or greater than 25% of their daily requirement, respectively. In Group 1, taurine concentrations were reduced to 35-49% of normal control values in plasma (p less than 0.01), platelets (p less than 0.001), lymphocytes (p less than 0.005), and erythrocytes (p less than 0.001). Granulocyte taurine was not different from normal. A smaller decrease in taurine concentration was found in Group 2 patients; however, taurine levels were significantly below normal in their plasma and red cells. Thus, many patients undergoing long-term parenteral nutrition with little or no taurine intake are depleted of taurine in plasma and most blood cells. These findings suggest that taurine may be essential for these patients and should be added to solutions used for long-term parenteral nutrition. PMID- 3092632 TI - Leu-M1 immunoreactivity in nonhematopoietic neoplasms and myeloproliferative disorders. An immunoperoxidase study of paraffin sections. AB - Leu-M1 is a differentiation antigen present on human myelomonocytic cells, which also has been identified in Reed-Sternberg cells and variants of Hodgkin's disease. This study further defines the tissue distribution of Leu-M1, with immunoreactivity observed for neoplastic cells in 14 of 28 formalin-fixed, paraffin-embedded nonhematopoietic neoplasms. With the use of monoclonal antibodies and an indirect immunoperoxidase technic, Leu-M1 was detected in adenocarcinomas of various sites (breast, lung, colon, thyroid, pancreas, and stomach), in squamous cell and transitional cell carcinomas, and in a small-cell anaplastic carcinoma. Evaluation of a wide variety of myeloproliferative disorders indicated that Leu-M1 effectively characterized mature and immature monocytic cells and myeloid cells at late stages of granulopoiesis, but it was not a reliable marker for early myeloid cells including blasts. Leu-M1 monoclonal antibodies are a useful diagnostic reagent, particularly in the assessment of lymphoproliferative disorders, but must be used with extreme caution and full awareness of its staining profile. PMID- 3092633 TI - Chronic liver disease following community-acquired non-A, non-B hepatitis. AB - Chronic non-A, non-B hepatitis occurring in an urban American population was identified in 23 patients followed for more than six months after the onset of acute hepatitis. Eight of the 23 patients subsequently developed normal aminotransferase levels a mean of 12.3 months after the onset of hepatitis. Liver biopsies were obtained from 9 of the remaining 15 patients. Eight biopsies revealed abnormalities consistent with chronic persistent hepatitis. One revealed chronic active hepatitis. The probable source of hepatitis included blood transfusions in 4%, intravenous drugs in 43%, personal contact in 4%, and no known source in 48%. Normalization of aminotransferase activity could not be predicted by initial symptoms, physical findings, or laboratory values. This study suggests that the chronic liver disease following community-acquired non-A, non-B hepatitis is frequent and may have a benign course. PMID- 3092634 TI - Quality control testing of anti-sera with glutaraldehyde-treated antigens. AB - Glutaraldehyde-treated bacterial cells were used as the quality control organisms in agglutination and fluorescent antibody tests for group A Streptococcus; Salmonella groups A, B, and D; Shigella groups B, C, and D; and Neisseria gonorrhoeae. The antigen preparations were serologically reactive over a period of five months. PMID- 3092635 TI - Coronary artery deposition of factor VIII-related antigen in ischemic heart disease. AB - This study localized Factor VIII-related antigen (FVIIIRAg) directly in the intramural coronary arteries of patients with coronary artery disease (CAD). Assays were performed on myocardial autopsy sections from 17 patients with and 15 patients without CAD, using a monospecific FVIIIRAg antibody in the peroxidase immunoperoxidase technic. FVIIIRAg was quantified by a FVIIIRAg index (FRI), as a numerical score based on distribution, thickness, and extension of immunostaining. The mean FRI for the CAD patients was 55 +/- 11 and that for the control patients 12 +/- 5 (P less than 0.001). The increased amounts of in situ FVIIIRAg suggest this glycoprotein may be involved in the pathogenesis of atherosclerosis. PMID- 3092636 TI - Factor VIII activity as measured by an amidolytic assay compared with a one-stage clotting assay. AB - Factor VIII amidolytic activity was measured by a commercially available method and compared with clotting activity measured in a one-stage assay. Parallel assays with both methods were used for plasma samples from 40 blood donors with normal or high Factor VIII levels, 22 patients with hemophilia before or after treatment with Factor VIII concentrates, 10 patients with chronic liver disease, and 10 normal subjects with high Factor VIII levels after treatment with desmopressin. The results obtained with the amidolytic assay were highly correlated (r = 0.97) with those obtained in the one-stage clotting assay. There were no significant differences in the results with the two methods in any of the patient groups, although in two cases of mild hemophilia the amidolytic assay gave lower values than the clotting assay. The reproducibility of the amidolytic assay (coefficient of variation = 6%) was better than that of the clotting assay (12%) at both normal and low levels of Factor VIII. PMID- 3092637 TI - Glass bead sterilization of orthodontic bands. AB - The purpose of this study was threefold: to determine if bead sterilization is capable of sterilizing orthodontic bands, if so, to establish a minimal time for sterilization when bands are inoculated with bacteria and spores, and to compare bead sterilization to other methods of cleansing and disinfecting orthodontic bands used in the office setting. Ten bands per time trial inoculated with either Bacillus subtilis spores or Staphylococcus albus bacteria were used along with ten controls (inoculated but not placed in the bead sterilizer). The bands were placed one at a time into a 226 degrees C bead sterilizer for 15, 30, 45, and 60 seconds, transferred to a test tube with BHI broth, and incubated at 37 degrees C for 3 days. The results indicated that 15 seconds is required to sterilize bacteria and 45 seconds required for spores. If five bands were placed in the bead sterilizer simultaneously, twice the time was required for sterilization. Other techniques for disinfecting bands, such as a 5-second tap water rinse, 10 second soap scrub, 30-minute immersion in alcohol, and alcohol flame, were ineffective in killing bacteria or spores with one exception--the alcohol flame was capable of preventing growth on bands inoculated with Staphylococcus albus. PMID- 3092638 TI - Nutritional practices and outcome of extremely premature infants. AB - We analyzed the records of 182 newborns with birth weights under 1000 g, who survived longer than seven days, to determine risk factors for subacute mortality and morbidity. Statistical analysis using logarithm-linear modeling was used to identify complex interactions and to minimize confounding. Nosocomial infection, necrotizing enterocolitis, male gender, and chronic lung disease (CLD) were identified as independent risk factors for subacute mortality. Male gender and CLD were associated with increased mortality only among patients who received parenteral nutrition (PN). Moreover, PN, rather than enteral nutrition (EN), was a risk factor for delayed growth, nosocomial infection, and CLD. Delayed initiation of EN was associated with decreased necrotizing enterocolitis risk only among male infants with birth weights under 775 g. Our results do not support elective withholding of EN in other groups of extremely low-birth-weight infants. We conclude that indications for PN and for withholding initiation of EN in very-very-low-birth-weight infants need to be established by prospective studies. PMID- 3092639 TI - Sphincter of Oddi motility: developments in physiology and clinical application. PMID- 3092640 TI - Retroperitoneal paraganglioma in a patient with von Recklinghausen's disease. PMID- 3092641 TI - Quantitation of the monoclonal plasma cell component in bone marrow from patients with serum paraproteinemia and nondiagnostic marrow morphology. AB - Twenty-one patients with serum monoclonal gammopathy but lacking acceptable morphological evidence of myelomatosis were studied with reference to the degree, if any, of monoclonal plasma cell expansion in aspirated marrow samples, enriched for plasma cells and analysed with respect to light chain distribution. Four of these patients had a biopsy-proven plasmacytoma of bone. Bone marrow aspirated from sites distant to the tumor showed clear evidence of infiltration by monoclonal plasma cells in two of the cases studied; the other two patients had normal results. Of the 17 other cases, 14 showed evidence of a monoclonal plasma cell component qualitatively concordant with the serum paraprotein as one would expect. These cases could be subdivided into those with myeloma (six cases) and those with monoclonal gammopathy of undetermined significance (eight cases) on the basis of conventional biochemical and radiological criteria. Three of the 17 patients, however, did not show evidence of monoclonal plasma cell infiltration, despite the presence of lytic lesions. It is important to recognize this minority group that simulates myeloma but that may well reflect alternative pathology that has not been identified. PMID- 3092642 TI - IgG heavy-chain (Gm) allotypes in familial polyposis coli. AB - Serum samples from 40 Danish patients with familial polyposis coli and 105 normal blood donors were typed for eight Gm and one Km markers. The distribution of all Gm phenotypes as a group was significantly different in the patient population as compared to the controls. Examination of individual Gm phenotypes showed an increased frequency of Gm3;5,13 in the patients. PMID- 3092645 TI - Persistently elevated polychlorinated biphenyl levels from residual contamination of workplace surfaces. AB - A short-term follow-up study was performed on 55 workers in a gear plant exposed to PCB that contaminated the work surfaces. Current work did not involve the use of PCBs. Exposure was to residual PCB left behind by a capacitor company which formerly used the site. Elevated PCB levels were found in production area workers; these elevations persisted on retesting 1 year later. Efforts should be made to identify potentially toxic materials left behind on work surfaces of buildings before remodeling or reuse. PMID- 3092644 TI - Immunochemical studies on lactate dehydrogenase A subunit deficiencies. AB - In lactate dehydrogenase (LDH) A subunit deficiency, is there not only a lack of activity but also a lack of subunit production? We demonstrated three remarkable points to answer this question: There are no proteins that immunologically react with anti-A subunits. There are no heterotetramers that react with anti-B subunits. B subunits seem to be genetically produced at normal level, and all of them form only one isoenzyme, LDH-B4. From these points, we concluded that there is a complete lack of A subunit production or production of incomplete A subunits that can neither react with anti-A subunits nor form heterotetramers. PMID- 3092643 TI - Human tissue-type plasminogen activator gene located near chromosomal breakpoint in myeloproliferative disorder. AB - Plasminogen activators (PA) convert the inactive proenzyme plasminogen into plasmin, which is involved in the process of fibrinolysis, tissue remodeling, and cell migration. There are two distinct forms of PA: urokinase (u-PA) and tissue type plasminogen activator (t-PA). t-PA has higher affinity for fibrin and is the main form involved in thrombolysis. By in situ chromosomal hybridization and Southern blot analysis of somatic cell hybrid DNA, we have assigned the human t PA gene to chromosome 8, bands 8p12----q11.2. We have detected a common EcoRI restriction fragment length polymorphism within the t-PA gene that thus provides a precisely localized highly informative marker for genetic linkage studies. The t-PA gene localization coincides with a translocation breakpoint observed in myeloproliferative disorders. Whereas leukemic cells usually secrete both types of PA, a correlation exists between acute myeloid leukemic cells that release only t-PA and failure to respond to chemotherapy. PMID- 3092646 TI - Evaluating growth of bacteria and fungi in total nutrient admixtures. PMID- 3092647 TI - Cost analysis of a satellite pharmacy. AB - The cost-effectiveness of a satellite pharmacy that serves 100 beds in a 550-bed community teaching institution was determined. On one day six months before and one day six months after the satellite pharmacy was implemented, 30 patients were randomly selected for study from the 50-bed surgical-trauma unit and the 50-bed medical oncology unit served by the satellite. Data for the cost analysis were collected from the medical charts of these 60 patients; each patient's entire hospital stay was used for all calculations. Data collected included costs per patient day for drugs, i.v. therapy, and laboratory tests; total hospital costs per patient day; number of doses per patient day; and length of hospital stay. There were no significant differences in patient age or sex, length of hospital stay, or patient mix among patients studied before and after the satellite pharmacy was implemented. The cost per patient day for drugs was significantly less after the satellite pharmacy was implemented. A cost analysis based on this decrease in drug costs per patient day of $5.77 showed that an annual savings of $134,927 could be realized as a result of satellite pharmacy implementation. Implementation of a pharmacy satellite proved to be cost-effective, largely because of decreased drug costs. PMID- 3092648 TI - Sorption of four drugs to polyvinyl chloride and polybutadiene intravenous administration sets. AB - Sorption of nitroglycerin, isosorbide dinitrate, diazepam, and clomethiazole edisylate (chlormethiazole) to polyvinyl chloride (PVC) i.v. administration sets with and without cellulose propionate burettes and to polybutadiene (PBD) sets with and without methacrylate butadiene styrene (MBS) burettes was studied. All drugs (except chlormethiazole) were diluted with 0.9% sodium chloride injection (NS) in glass bottles or in the burette chambers. Initial samples of each solution were obtained from the bottle or from the burette, and effluent samples were collected at various times up to 240 minutes from the sets without burettes and up to 90 minutes from the sets with burettes. For nitroglycerin, flow rates of 0.5 and 1.0 mL/min were used without the burette. The effect of priming the tubing before adding drug to the burette was studied for diazepam. Triplicate samples were analyzed for nitroglycerin and isosorbide dinitrate by high performance liquid chromatography and for diazepam and chlormethiazole by ultraviolet spectrophotometry. Up to 50% potency of chlormethiazole and nitroglycerin, 15-25% of isosorbide dinitrate, and 13-20% of diazepam was lost to PVC sets without burettes, and an additional 10-15% loss of each drug resulted when PVC sets with burettes were used. Less sorption of nitroglycerin to the PVC sets occurred at the higher flow rate, but flow rate through the PBD sets did not affect sorption. Priming the tubing before adding diazepam to the burette did not affect final drug delivery. No loss to PBD sets was observed for nitroglycerin, isosorbide dinitrate, and diazepam; loss of chlormethiazole to PBD was 7-13%. Drug potency in effluent from PBD sets was not affected by presence or absence of a burette.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092649 TI - Protective and therapeutic effects of gastrointestinal prostaglandins. Enprostil: a new modality. Proceedings of a symposium. November 13-14, 1985, Toronto, Canada. PMID- 3092650 TI - Protective effects of the synthetic prostaglandin enprostil on the gastric microvasculature after ethanol injury in the rat. AB - The effect of pretreatment with the synthetic prostaglandin E2 analogue enprostil on ethanol damage to the rat gastric mucosa was studied. Microvascular casts were prepared and studied by scanning electron microscopy. The permeability of mucosal capillaries to fluorescein isothiocyanate-labeled albumin (FITC-albumin) given intravenously was examined by fluorescence microscopy. After administration of ethanol (1 ml absolute ethanol intragastrically) alone, casts showed gross disruption of the normal structure, with large foci of loss of the patency of the capillary network, frequently extending to the level of the submucosal vessels. There was exudation of casting material into the mucosal interstitium and onto the surface of the cast. After administration of FITC-albumin, there was a marked increase in interstitial fluorescence throughout the full thickness of the mucosa. Pretreatment with enprostil (1 microgram/kg intragastrically) prevented most of the damaging effects of ethanol. Increased microvascular permeability to FITC-albumin was noted only in the most superficial layers of the mucosa. These studies characterize the effect of ethanol on the gastric microvasculature and indicate that pretreatment with enprostil restricts this damaging effect to the superficial mucosal microvessels. These studies further suggest that microvascular damage is an early event in ethanol injury, apparently preceding epithelial erosion. PMID- 3092651 TI - Stimulatory effect of enprostil, an anti-ulcer prostaglandin, on gastric mucus secretion. AB - Enprostil, a synthetic analogue of prostaglandin E2, is known to be a potent inhibitor of gastric acid secretion, and has marked anti-ulcer activity in rodents. Enprostil was administered in doses ranging from 15 to 250 micrograms/kg to rats prepared using the Shay procedure. Three hours later, the rats' stomachs were removed and processed either for the chemical determination of mucus, or for scanning electron microscopy. For the chemical determination, the secreted gastric juice was removed and the adherent gastric mucus was eluted with 2 M sodium chloride. The anthrone method was used to determine the mucus present. Enprostil was found to significantly increase gastric mucus at a dose of 60 micrograms/kg when measured by the anthrone test. Enprostil administered by the oral route was most effective in stimulating mucus secretion, suggesting a local or topical action of enprostil on mucus-secreting cells. Scanning electron microscopy of rat fundic mucosa after enprostil administration (50 to 100 micrograms/kg) revealed the presence of thin veil-like layers covering the epithelial surface, which was interpreted as an increase in mucus secretion. Higher magnifications (X 2,000) clearly showed the layers of mucus covering the surface epithelial cells. Enprostil's apparent increase of gastric mucus secretion may contribute to its anti-ulcer activity and may promote gastric healing. PMID- 3092653 TI - Effect of a single oral dose of enprostil on gastric secretion and gastrin release. Studies in healthy volunteers and patients with pernicious anemia. AB - In healthy human volunteers, a single oral dose of enprostil (35 micrograms) inhibited basal gastric acid output by a mean of 71 percent, pentagastrin stimulated output by 46 percent, sham-meal-stimulated output by 48 percent, and histamine-stimulated output by 16 percent. In each case, there was a reduction in both the volume and acidity of the gastric juice. Pepsin output was unchanged. Although enprostil increased the gastric pH, it did not induce basal or post prandial hypergastrinemia. In patients with hypergastrinemia secondary to achlorhydria, enprostil lowered the basal gastrin level and reduced or abolished the post-prandial gastrin rise in a dose-related fashion. Enprostil reduces basal and stimulated gastric acid secretion and inhibits gastrin release. PMID- 3092652 TI - Effects of enprostil on platelets, endothelial cells, and other cell types, and second messenger systems by which these effects are mediated. AB - In human blood platelets, thromboxane A2, prostaglandin E2, and its analogue enprostil activate protein kinase C and promote the second phase of aggregation, whereas prostacyclin and prostaglandin E1 activate adenylate cyclase and inhibit aggregation. In each case, a characteristic group of proteins is phosphorylated following agonist binding. These observations may be related to the inhibitory effect of enprostil on the activation of adenylate cyclase in gastric parietal cells, which follows binding of histamine to H2 receptors. Another system in which enprostil opposes the effect of histamine is the microvasculature. Histamine binds to H1 sites on endothelial cells and induces changes in their shape that allow macromolecules to pass between them into the extravascular compartment. This effect may be mediated by activation of protein kinase C. Pretreatment with enprostil antagonizes the increase in vascular permeability induced by histamine and presumably other inflammatory mediators. Preservation of the integrity of the microvasculature of the gastric mucosa against the effects of cyclo-oxygenase inhibitors, ethanol, and other damaging agents may contribute to the mucosal protective effects of enprostil and some other prostaglandins. PMID- 3092654 TI - Enprostil, a synthetic prostaglandin E2 analogue, inhibits meal-stimulated gastric acid secretion and gastrin release in patients with duodenal ulcer. AB - The effect of enprostil, a synthetic dehydro-prostaglandin E2, on meal-stimulated gastric acid secretion and gastrin release was studied in six patients with inactive duodenal ulcer disease. Each subject underwent seven tests in random order on separate days: placebo intragastrically and intraduodenally; enprostil 35 and 70 micrograms both intragastrically and intraduodenally; and ranitidine 150 mg intragastrically. After measuring basal gastric acid secretion and gastrin release, a liquid meal (500 ml, pH 5.5, 40 g protein, 30 g fat, 30 g carbohydrate, 550 Kcal, 768 mOsm) was given. Gastric acid secretion and gastrin release were measured over the next four hours. A second identical meal was instilled and both parameters were measured for an additional four hours. Thirty five and 70 micrograms of enprostil administered intragastrically reduced total eight-hour gastric acid secretion by 58 percent and 82 percent, respectively (p less than 0.05). The 35 and 70 microgram doses administered intraduodenally decreased gastric acid secretion by 67 percent and 91 percent, respectively (p less than 0.05 compared with placebo). Ranitidine suppressed gastric acid secretion by 95 percent, which was similar to the suppression achieved with the 70 microgram dose of enprostil. The total meal-stimulated integrated gastrin response was significantly suppressed by both intragastric doses of enprostil and by the 70 microgram dose given intraduodenally (p less than 0.05). Compared with placebo, the 35 microgram intragastric and intraduodenal doses decreased the integrated gastrin response by 73 percent and 72 percent, respectively. The 70 microgram intragastric and intraduodenal doses of enprostil reduced the integrated gastrin response by 90 percent and 125 percent, respectively. Ranitidine did not alter the integrated gastrin response. It is concluded that enprostil significantly inhibited both meal-stimulated gastric acid secretion and gastrin release. The response to enprostil occurred in a dose-dependent manner and was similar regardless of the route of administration. PMID- 3092655 TI - Reduction by enprostil of aspirin-induced blood loss from human gastric mucosa. AB - Enprostil's ability to protect human gastric mucosa against aspirin-induced damage was investigated in a controlled study. Damage was assessed as blood loss into gastric washings measured spectrophotometrically using orthotolidine in the presence of hydrogen peroxide. Phenol red was used to correct for recovery rates. Five doses of aspirin, 600 mg, given over 48 hours increased blood loss ninefold compared with placebo. Administration of enprostil 35 micrograms twenty minutes before each dose of aspirin halved this blood loss. After enprostil administration, the pH of both aspirated gastric juice and washings was significantly elevated, suggesting that an antisecretory dose had been used. Increased losses of phenol red occurred following both aspirin and enprostil administration, suggesting enhanced gastric emptying or possible absorption of phenol red as a result of aspirin damage. Side effects related mainly to the alimentary system were associated with enprostil treatment. Enprostil reduced aspirin-induced mucosal blood loss but the mechanism is unclear. PMID- 3092656 TI - Protective effect of enprostil against aspirin-induced gastroduodenal mucosal injury in man. Comparison with cimetidine and sucralfate. AB - A single-blind endoscopic study was undertaken to test the relative efficacy of enprostil, a synthetic analogue of prostaglandin E2, cimetidine, and sucralfate in the prevention of aspirin-induced gastroduodenal mucosal injury. Fifty healthy, non-smoking male volunteers completed the study after having been randomly assigned to receive two weeks of therapy with one of the following regimens: enprostil 35 micrograms twice daily; enprostil 35 micrograms in the morning; cimetidine 200 mg three times daily and 400 mg at night; sucralfate 1 g four times daily; or placebo. In the second week, aspirin (900 mg three times daily) was also administered. Endoscopies were performed before and after the aspirin phase of the study, and lesions (mucosal erosions plus submucosal hemorrhages) were counted in the stomach and duodenal bulb. All treatments were superior to placebo (p less than 0.05). The mean number of lesions in the 70 micrograms enprostil group (8.5) was significantly less than in the 35-micrograms enprostil group, (11.1), the sucralfate group (12.4), or the placebo group (16.0); the benefit over cimetidine (10.1), however, was not statistically significant. The protective effect of enprostil was greatest in the antrum, the site of maximal mucosal injury. Gastrointestinal side effects were reported in all groups, though abdominal pain and dyspepsia were noted more frequently in those taking enprostil. PMID- 3092657 TI - Treatment of duodenal ulcer with enprostil, a synthetic prostaglandin E2 analogue. AB - Enprostil is a synthetic prostaglandin E2 analogue developed by Syntex. In a randomized, double-blind trial involving 128 patients with duodenal ulcer disease, four weeks of treatment with enprostil at doses of 70 micrograms twice daily and 35 micrograms twice daily produced healing rates (78 percent and 65 percent, respectively) that were statistically significantly higher than the placebo rate (39 percent; p less than 0.05). In a subgroup of smokers, ulcer healing occurred with statistically significantly greater frequency at both the high dose (70 percent) and the low dose (60 percent) when compared with the rate in the placebo group (32 percent; p less than 0.05). The only clinically important side effect was diarrhea, which was generally mild, self-limited, and of short duration. This study demonstrated that enprostil is highly effective in the treatment of duodenal ulcer and has a favorable safety profile. PMID- 3092658 TI - Treatment of duodenal ulcer with enprostil, a prostaglandin E2 analogue. AB - Enprostil is a synthetic prostaglandin E2 analogue with gastric anti-secretory, cytoprotective, and gastrin lowering properties. The current multi-center, double blind, placebo-controlled study was undertaken to evaluate the efficacy and safety of enprostil (35 micrograms twice daily) for the treatment of duodenal ulcers. The study enrolled 87 patients between the ages of 18 and 85 with an endoscopically proved duodenal ulcer between 0.5 and 3.0 cm in its longest dimension and with no other serious medical conditions or abnormal laboratory tests results. Treatment groups were comparable in age, sex, smoking status, ulcer history, and baseline ulcer size. The results indicated that the healing rate for enprostil at two weeks was 38 percent, compared with a placebo rate of 23 percent (p = 0.151). At four weeks, 70 percent of the enprostil-treated patients had healed ulcers, compared with 49 percent of the placebo-treated patients, a statistically significant difference (p = 0.048). Although within the enprostil group the healing rate was higher in nonsmokers (86 percent) than in smokers (58 percent), this difference did not reach statistical significance. Side effects included diarrhea (14 percent) and headache (7 percent). These results indicate that 35 micrograms of enprostil twice daily provides effective and safe therapy for patients with duodenal ulcer. PMID- 3092660 TI - Treatment of gastric ulcer with enprostil. AB - This study evaluated the efficacy of two dosage levels of enprostil in 129 patients with gastric ulcer disease. Patients with endoscopically diagnosed gastric ulcer were randomly assigned to receive enprostil 70 micrograms, enprostil 35 micrograms, or a matching placebo capsule twice daily for six weeks. Ulcer healing rates were similar in all treatment groups after two weeks of therapy, but began to show some differences in favor of the enprostil treatment groups after four weeks. Greater differences were noted after six weeks of therapy, with healing rates of 70 percent in the 70-micrograms enprostil group, 82 percent in the 35-micrograms enprostil group, and 50 percent in the placebo group. The six-week healing rate in the 35-micrograms enprostil group was significantly greater than the placebo rate (p = 0.005). Comparison of healing rates in the active treatment groups and the placebo group after six weeks of therapy showed a correlation between therapeutic effect and ulcer size at baseline. This trend is illustrated by a 24 percent difference between the 35 micrograms enprostil group and the placebo group among patients with small (3 to 9 mm) ulcers, compared with a 46 percent difference between these two groups among patients with large (20 to 30 mm) ulcers. Thus, the effectiveness of enprostil is more readily demonstrable in patients with larger ulcers. PMID- 3092659 TI - Comparison of enprostil and cimetidine in active duodenal ulcer disease. Summary of pooled European studies. AB - Data were combined for statistical analysis from four European trials comparing enprostil (35 micrograms twice daily) with cimetidine (400 mg twice daily) in the treatment of duodenal ulcer, using a double-blind, randomized design with endoscopic control. A total of 369 patients entered the trials, of whom 348 were eligible for the efficacy analyses and 362 for the safety analyses. Patients were allowed antacids as needed. The pooled cumulative healing rates at two, four, and six weeks were 40, 75, and 84 percent, respectively, for enprostil and 42, 77, and 87 percent, respectively, for cimetidine. There were no significant differences between treatments. Healing rates in both groups were reduced in smokers, in those with larger ulcers at baseline, and in those who reported a higher consumption of alcohol. Age, however, had no effect on healing rates. Digestive system complaints were reported more frequently in the enprostil group, whereas central nervous system complaints were more than twice as frequent in the cimetidine group. PMID- 3092661 TI - Comparative clinical trial of enprostil and ranitidine in the treatment of gastric ulcer. AB - In a randomized, double-bind, parallel, multi-clinic study, the safety and efficacy of enprostil (35 micrograms twice daily) and ranitidine (150 mg twice daily) were compared in the treatment of active gastric ulcer in 93 outpatients (47 enprostil-treated patients and 46 ranitidine). The two treatment groups were well matched for demographic characteristics. The healing rates in the enprostil group were 22, 58, 80, and 86 percent at two, four, six, and eight weeks, respectively. The corresponding rates in the ranitidine group were 22, 66, 84, and 89 percent. None of these differences was statistically significant. The area of the ulcer at baseline and smoking status did not appear to influence healing rates. There were no significant differences between treatment groups in time to relief of ulcer symptoms, frequency of daytime or nighttime ulcer pain, or antacid use. Side effects attributable to enprostil treatment were diarrhea (10 percent versus 6 percent with ranitidine), gastrointestinal pain, and vomiting. These side effects, however, did not influence the patients' assessments of their overall response to enprostil and ranitidine therapy. Six enprostil-treated patients and one ranitidine-treated patient withdrew from the trial prematurely because of adverse experiences. Monitoring of clinical laboratory test results showed no significant changes in the two treatment groups. This study demonstrates that a prostaglandin E2 analogue, enprostil, in a dose of 35 micrograms twice daily, is similarly safe and effective as ranitidine in the treatment of active gastric ulcer. PMID- 3092662 TI - Prostaglandins in congestive heart failure and the effects of nonsteroidal anti inflammatory drugs. AB - With the failure of the heart as a pump, there ensues a series of neurohumoral compensations that defend organ perfusion at the expense of alterations in cardiac filling pressures and the distribution of blood flow to various regional circulations. Activation of the sympathetic nervous system and the renin angiotensin II-aldosterone system and increases in circulating arginine vasopressin maintain arterial blood pressure by producing systemic arteriolar vasoconstriction and the renal retention of salt and water. Constriction of the efferent arterioles in the kidney by angiotensin II and norepinephrine promotes reabsorption of glomerular filtrate in the peritubular capillaries and maintains glomerular filtration in the face of declines in glomerular plasma flow and the glomerular permeability-surface area ultrafiltration coefficient. In resting, sodium-replete, conscious animals and humans, pharmacologic inhibition of renal cyclo-oxygenase by nonsteroidal anti-inflammatory drugs has little or no effect on renal hemodynamics. However, electrical or reflex stimulation of the renal nerves, intrarenal infusion of angiotensin II, or infusion of arginine vasopressin stimulates the release of vasodilator prostaglandins from the kidneys. In sodium-depleted animals or humans, and when cardiac output decreases, there is an increase in total peripheral vascular resistance but little change in renal vascular resistance. Increased renal synthesis of vasodilator prostaglandins (presumably by the blood vessels) maintains renal blood flow despite increased release of renin and norepinephrine from the kidneys. In these situations, pharmacologic inhibition of renal cyclo-oxygenase is accompanied by marked reductions in renal blood flow and glomerular filtration rate. When this occurs in patients with advanced heart failure, reversible oliguric renal failure may result. In this setting, cyclo-oxygenase inhibition may also increase arterial pressure and induce additional depression of cardiac function. Recent data indicate that blood vessels have the capacity to synthesize the sulfidopeptide leukotrienes C4, D4, and E4, which can constrict peripheral and renal blood vessels and alter vascular permeability. The vascular cell types responsible for leukotriene C4 synthesis and the potential roles of these vasoactive eicosanoids in kidney and other regional circulations are currently under study. PMID- 3092663 TI - Measurement of renal and non-renal eicosanoid synthesis. AB - Enzymatic metabolites of arachidonic acid (eicosanoids) have potent biologic actions in vitro that suggest their pathophysiologic importance in vivo. To address this possibility, analytic methodology has been developed to permit study of the formation of these compounds in vivo. Both radioimmunoassay and gas chromatography-mass spectrometry have been used to measure stable but biologically inactive metabolites of the eicosanoids. Although indirect, such measures are presently the most reliable, because superfusion-bioassay lacks the specificity and precision necessary for quantitative analysis of eicosanoid formation in vivo. Measurement of eicosanoids and their hydration products and metabolites in urine represents a non-invasive approach to the assessment of eicosanoid biosynthesis. Although a tissue of origin cannot be ascribed definitely to a compound measured in urine, corroborative evidence can be obtained to indicate the predominant tissue source under physiologic and pathologic conditions. This relates particularly to the distinction between renal and extrarenal biosynthesis of these compounds. Although similar limitations apply to the measurement of eicosanoids in plasma, these may also be confounded by sources of artifact related to blood withdrawal. In the case of thromboxane B2, these concerns have been addressed by the development of methods to measure its enzymatic metabolites in plasma. Finally, formation of eicosanoids may be studied in localized compartments such as lavage or synovial fluid. Such an approach has recently provided biochemical evidence for increased formation of prostacyclin and prostaglandin E2 at the platelet-vascular interface during selective inhibition of thromboxane synthase in humans. PMID- 3092664 TI - Glomerular prostaglandins, angiotensin II, and nonsteroidal anti-inflammatory drugs. AB - The glomerulus can, in part, regulate its own flow and filtration characteristics, both of which are determinants of the glomerular filtration rate. This occurs in part as the result of interactions between vasoconstrictors, e.g., angiotensin II (AII), and the vasodilatory prostaglandins E2 or I2. It is well accepted that these prostaglandins modulate the constrictor effects of AII on systemic and renal vasculature. Experimental data accumulated from micropuncture studies, analyses of isolated glomeruli in vitro, and glomerular mesangial cell cultures also support the hypothesis that AII-stimulated production of vasodilatory prostaglandins attenuates AII-induced constriction at the glomerular level as well. These studies help to explain the deleterious actions of nonsteroidal anti-inflammatory drugs on glomerular filtration in clinical conditions associated with a decreased effective blood volume and, therefore, activation of AII and other neurohormonal constrictors. These results have also furthered our understanding of the role of prostaglandins in maintaining renal function in human and experimental renal diseases that may be associated with enhanced hormonal constrictor activity. PMID- 3092665 TI - Interaction of nonsteroidal anti-inflammatory drugs with antihypertensive and diuretic agents. Control of vascular reactivity by endogenous prostanoids. AB - Indomethacin and some other nonsteroidal anti-inflammatory drugs partially antagonize the blood pressure lowering effect of drugs used to treat hypertension. They can also produce a mild elevation of blood pressure in normotensive individuals. The elevated arterial pressure caused by these agents is associated with increases in the vascular resistance of mainly the renal and splanchnic beds. This may be due to direct inhibition of the synthesis of vasodilator prostanoids, or it may be due to indirect potentiation of the action of the sympathetic nervous system or of angiotensin II. Nonsteroidal anti inflammatory drugs also cause renal retention of sodium and this probably contributes to their hypertensive effects. In humans, the sodium retention may involve increased reabsorption in the proximal tubule. Although a direct tubular action is possible, these drugs may change proximal sodium reabsorption by their vascular effects. However, the exact mechanism is not understood. These interactions are clinically significant and may complicate the treatment of common diseases. PMID- 3092666 TI - Effects of nonsteroidal anti-inflammatory drugs in healthy subjects. AB - Nonsteroidal anti-inflammatory drugs inhibit cyclo-oxygenase activity and thereby reduce prostaglandin synthesis. Studies in humans have used these cyclo-oxygenase inhibitors to examine the role of prostaglandins in controlling renal function. Although short-term studies have demonstrated reductions in effective renal plasma flow, glomerular filtration rate, urinary sodium excretion, and plasma renin activity, long-term administration of nonsteroidal anti-inflammatory drugs does not result in significant or clinically important changes in renal function in normal human subjects. If healthy volunteers are placed on low-sodium diets or treated with diuretics, both renal hemodynamics and salt and water excretion can become prostaglandin-dependent. Studies in normal subjects suggest that sulindac, a nonsteroidal anti-inflammatory drug that undergoes biotransformation in the kidney, does not inhibit renal prostaglandin synthesis or urinary sodium excretion under basal conditions but may impair furosemide-stimulated prostaglandin synthesis and changes in renal function. Doses of sulindac that spare basal renal cyclo-oxygenase do inhibit extrarenal cyclo-oxygenase. The mechanism responsible for this biochemical selectivity of sulindac is not related to a differential sensitivity of the renal cyclo-oxygenase to the active metabolite of sulindac, sulindac sulfide. Sulindac sulfide, in concentrations as low as 1 nM, was equipotent to indomethacin as an inhibitor of prostaglandin E2 synthesis in primary cultures of three renal cell lines. Appropriate clinical use of all nonsteroidal anti-inflammatory drugs, including sulindac, requires careful consideration of risk factors that predispose to nephrotoxicity and careful monitoring when administered to patients at risk. PMID- 3092667 TI - Renal effects of nonsteroidal anti-inflammatory drugs in chronic glomerular disease. AB - In contrast to a variety of clinical conditions characterized by ineffective circulatory volume, chronic glomerular disease is not usually associated with increased circulating levels of vasoconstrictor hormones. However, a reduction in glomerular prostacyclin production can possibly account for the prostaglandin dependence of renal function in these patients by virtue of the enhanced constrictor effects of angiotensin II on glomerular arterioles and mesangium. The reduction of renal function induced by a nonselective cyclo-oxygenase inhibitor is inversely related to the basal prostacyclin production. Increased renal synthesis of vasoconstrictor thromboxane A2, as noted in patients with systemic lupus erythematosus, might contribute to the cyclo-oxygenase dependence of renal function. Aspirin as well as a variety of structurally unrelated nonsteroidal anti-inflammatory drugs reduce renal function in systemic lupus erythematosus patients. However, the functional consequences of renal cyclo-oxygenase inhibition are partially attenuated in patients with lupus nephritis vis-a-vis other forms of chronic glomerular disease because of concomitant suppression of enhanced glomerular thromboxane A2 production. Animal data consistent with a prevailing functional significance of vasodilator prostaglandins have also been reported. Short-term administration of sulindac at the recommended dosage is relatively safe in patients with chronic glomerular disease because of selective sparing of glomerular cyclo-oxygenase activity. The long-term consequences of selective versus nonselective cyclo-oxygenase inhibition remain to be established in humans. The beneficial effects of a combination of aspirin and dipyridamole in slowing the deterioration of renal function in patients with membranoproliferative glomerulonephritis does provide a rationale for exploring the effects of low-dose aspirin (i.e., 0.5 to 1.0 mg/kg per day), which most effectively suppresses platelet thromboxane A2 production without interfering with renal prostacyclin synthesis. PMID- 3092668 TI - Hypopituitarism following radiation therapy of pituitary adenomas. AB - Pituitary function was evaluated before and after supervoltage radiotherapy for a pituitary adenoma in 35 patients; 22 had had prior surgical treatment, and 13 had not. For comparison, pituitary function was also followed concurrently in another 10 patients whose pituitary adenomas were treated surgically, but who did not receive subsequent radiotherapy. Following radiotherapy, deficiencies of adrenal, thyroid, and gonadal function developed in 67, 55, and 67 percent of the patients who had previously been treated surgically during a mean of 4.2 years of observation, and in 55, 15, and 50 percent of the patients who did not have prior surgery during the subsequent five years. In contrast, in patients who had previously been treated surgically and who did not receive radiation, deficiencies of these hormones developed in only 13, 13, and 0 percent during four years of observation. It is concluded that supervoltage radiotherapy for pituitary adenoma, especially when preceded by surgical treatment, frequently produces, during the ensuing four to five years, deficiencies of pituitary hormones that had been secreted normally prior to irradiation. PMID- 3092669 TI - Intrauterine intravascular transfusions for severe red blood cell isoimmunization: ultrasound-guided percutaneous approach. AB - Eight pregnancies with severe red blood cell isoimmunization were managed with use of an intravascular approach for intrauterine transfusions. Fetoscopy was not employed, and the procedures were performed percutaneously under direct ultrasound visualization. A total of 16 of 18 attempted transfusions were successfully performed, with four fetuses requiring more than one transfusion. Technical aspects of the procedure as well as its indications, advantages, and drawbacks are discussed. PMID- 3092670 TI - von Willebrand's disease and pregnancy: management during delivery and outcome of offspring. AB - Six patients having different subtypes of von Willebrand's disease were followed up during eight complete pregnancies. Two additional pregnancies terminated in spontaneous abortions. Five pregnancies ended in cesarean section either because of obstetric problems (three) or electively (two) to avoid infant bleeding. Three deliveries were complicated by vaginal bleeding attributed to von Willebrand's disease, while bleeding during two deliveries had clear obstetric causes. Only two deliveries were associated with no bleeding complications. Five newborn babies were found to have von Willebrand's disease. One of them was born with a head hematoma. Management, which included cryoprecipitate and desmopressin (Stimate), is discussed. It is important to manage each case individually since obstetric parameters and severity of bleeding disorder must be known before treatment is planned. PMID- 3092671 TI - Midtrimester amniotic fluid delta optical density at 450 nm in normal pregnancies. AB - Spectrophotometric analysis of amniotic fluid has become the standard for assessing the fetal condition in Rh-immunized pregnancies. Serial amniocentesis is usually started at 28 to 29 weeks of gestation unless the antibody titer or history indicates it should be done earlier. This study presents the values from 14 to 20 weeks in normal pregnancies, which will also assist in evaluating pathologically elevated values. PMID- 3092672 TI - Evolution of cranial blood drainage in hominids: enlarged occipital/marginal sinuses and emissary foramina. AB - Physiological studies of cranial blood flow in humans in reclining vs. upright postures suggest that selection for bipedalism was correlated with the establishment of epigenetic adaptations for delivering blood preferentially to the vertebral plexus of veins, depending upon momentary respiratory and postural constraints. The frequencies of vascular/osteological channels used to deliver blood to the vertebral plexus of veins were determined for samples of African pongids, various taxa of fossil hominids, and extant Homo sapiens. These channels include an enlarged occipital/marginal (O/M) sinus system, multiple hypoglossal canals, and foramina that conduct emissary veins: posterior condyloid, mastoid, occipital, and parietal. The African pongid, and therefore presumably the ancestral prebipedal hominoid, condition is characterized by low frequencies of all of these routes except multiple hypoglossal canals. The earliest known bipeds (Australopithecus afarensis) and robust australopithecines are characterized by fixation of enlarged O/M sinus systems. Robust australopithecines are also characterized by apparently low frequencies of mastoid and parietal foramina, and high frequencies of multiple hypoglossal canals and posterior condyloid foramina. In gracile australopithecines and subsequently living hominids, trends towards increased frequencies of mastoid and (later) parietal emissary foramina coincide with a trend towards decreased frequencies of an enlarged O/M sinus system and multiple hypoglossal canals. These findings suggest that selection for bipedalism initially resulted in epigenetic adaptations for routes to deliver blood to the vertebral plexus including an enlarged O/M sinus system and hypoglossal canals, but that the pressures underlying these adaptations relaxed as bipedalism became established, and other routes for delivering blood to the vertebral plexus of veins were either directly or indirectly selected for, perhaps in conjunction with a changing architecture of the skull. A systematic implication of this study is that robust australopithecines are descendants of A. afarensis rather than of A. africanus. PMID- 3092673 TI - Dental reduction in post-pleistocene Nubia. AB - Tooth size changes among Nubian archaeological populations dating from the Mesolithic through the Christian era, a period of approximately 12,000 years, are analyzed. Standard length and breadth dimensions of all permanent teeth from several cultural horizons are combined to form three large samples: Mesolithic, 10000-70000 B.C.; Agriculturalist, 3300-1100 B.C. (A-group, C-group, Pharaonic); and Intensive Agriculturalist, A.D. 0-1400 (Meroitic, X-Group, Christian). Such information not only fills a void in the knowledge of Nubian skeletal biology, but also provides a much needed African reference point for the comparison of tooth size data among anatomically modern Homo sapiens from various regions of the world. Changes in mean tooth size and associated t-tests reveal strong and significant reduction in dental size between the Mesolithic and Agriculturalist samples, followed by a continued although diminished trend of reduction for only the molar teeth between the two Agriculturalist groups. These patterns are best observed by examining tooth breadths, which are considered as the most reliable indicator of tooth size. Previously published odontometrics of the Nubian Mesolithic are briefly compared to the findings of this diachronic analysis of Nubian dental change. PMID- 3092674 TI - Activation of Cl-dependent K transport in Ehrlich ascites tumor cells. AB - N-ethylmaleimide (NEM) treatment of steady-state Ehrlich cells induces a substantial net loss of cellular KCl and cell shrinkage. The majority of the initial K loss is Cl dependent. From estimates of membrane potential it is concluded that the NEM-induced KCl loss is electroneutral. The effect of NEM on H extrusion by cells in 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) containing medium showed that only an insignificant part of the K loss could be attributed to an activation of a K-H exchange system. Consequently, NEM appears to activate a K-Cl cotransport, which causes cell shrinkage. The anion preference of the K loss is Cl greater than Br much greater than SCN = NO3. NEM also seems to inhibit a Cl-dependent Na uptake previously described in shrunken cells. Addition of NEM to cells undergoing regulatory volume decrease after swelling in hyposmotic media results in a Cl-dependent acceleration of cell shrinkage, suggesting that a Cl-dependent component of K efflux is induced by NEM also in swollen cells. A Cl-dependent K efflux is also activated in Ca-depleted cells or at reduced extracellular pH after cell swelling. Under isotonic conditions activation of Cl-dependent K flux after Ca depletion or pH reduction could not be demonstrated. The combined results show that Ehrlich cells possess a latent K-Cl cotransport that becomes active after changes in the state of SH groups, regardless of the initial cell volume. A similar K-Cl cotransport is activated in hypotonically swollen cells after Ca depletion or after reduction of the extracellular pH. PMID- 3092675 TI - Evaluation of granule exocytosis in toad urinary bladder. AB - Addition of phorbol myristate acetate (PMA) to the mucosal bathing solution induces exocytosis of the granules found in the apical cytoplasm of toad urinary bladder epithelial cells. Because mucosal application of PMA also increases epithelial water permeability in the complete absence of vasopressin, these observations have suggested that granules might have a role in mediating the permeability response to vasopressin. From electron microscopic immunolocalization studies we have identified a 70-kDa protein as a component of the apical surface glycocalyx that is stored in the granules. Using antibodies to this protein in a competitive immunoassay, we found that addition of PMA to the mucosal side results in more than a fourfold increase in antigen release into the mucosal bath. The amount of antigen detectable on the mucosal surface of the cells was doubled by mucosal PMA exposure. Serosal application of PMA or addition of the inactive analogue phorbol didecanoate to either surface failed to produce significant antigen release. These results are consistent with electron microscopic studies showing exocytosis of granules only with mucosal exposure to PMA. However, immunoassay of granule antigen after vasopressin stimulation of water permeability failed to show a detectable change in granule exocytosis. We conclude that granule exocytosis does not play an important role in mediating vasopressin-induced changes in permeability. PMID- 3092676 TI - Effects of mast cell-derived mediators on epithelial cells in canine trachea. AB - We examined the interaction between mast cell-derived mediators and the electrical and ion transport properties of canine tracheal epithelium. We compared the effect of mediators released by immunologic challenge of sensitized lung parenchyma with that of mediators released from canine mastocytoma cells challenged with calcium ionophore A23187. Short-circuit current (Isc) increased by 19.2 +/- 3.0 microA/cm2 in response to mediators released from sensitized lung fragments challenged with ragweed antigen. This effect was not due to histamine. When the epithelial tissues were pretreated with indomethacin, the same mediator supernatant increased Isc by only 3.8 +/- 4.3 microA/cm2. The mediators released from 10(7) mastocytoma cells challenged with calcium ionophore increased Isc by 25.1 +/- 13.6 microA/cm2. In the presence of indomethacin, the Isc increased by 2.0 +/- 0.4 microA/cm2. Mastocytoma-derived mediators produced an increase in net chloride secretion without a significant effect on net sodium absorption. This study provides direct evidence that mast cell-derived mediators can stimulate epithelial ion transport in canine trachea and suggests that the effect is indirect and dependent on intact cyclooxygenase pathways in the tracheal epithelium. PMID- 3092677 TI - Forskolin effects on frog and rabbit corneal epithelium ion transport. AB - The effects of forskolin on the electrophysiological parameters of the isolated corneal epithelium from bullfrog (Rana catesbeiana) were investigated. Forskolin stimulated the short-circuit current (SCC) and transepithelial potential difference (PDt), while reducing the transepithelial resistance. These effects were absent in Cl- -free bathing solutions. Furosemide, added either before or after forskolin, completely blocked the effects. Epinephrine and A23187, added after forskolin, produced only a small additional stimulation of the SCC. Propranolol neither blocked nor reduced the effect of forskolin. Forskolin increased the stroma to tear 36Cl flux by 61% and the tear to stroma 36Cl flux by 64%. Intracellular recordings showed that forskolin depolarized the potential difference across the apical membrane and reduced the apical/basolateral resistance ratio. Intracellular recordings in the isolated rabbit epithelium showed the same effects by forskolin except that there was only a brief stimulation of PDt, after which it stabilized slightly below the control level. These results are consistent with an increase in apical membrane permeability similar to that produced by adenosine 3',5'-cyclic monophosphate, epinephrine, and the Ca2+ ionophore A23187. PMID- 3092678 TI - Mechanism of increased hepatic concentration of carnitine by clofibrate. AB - Our previous studies have shown that treatment of rats with clofibrate, a hypolipidemic drug, greatly increases the total concentration of carnitine in the liver (H. S. Paul and S. A. Adibi, J. Clin. Invest. 64: 405-412, 1979). In the present experiment we have investigated some possible mechanisms to account for this increase. Clofibrate treatment (30 mg/100 g rat/day for 2 wk) increased significantly the concentration (nmol/g, mean +/- SE, 6 rats) of both free (289 +/- 21 vs. 1,747 +/- 131) and acylcarnitine (87 +/- 11 vs. 412 +/- 42). These increases were not the result of redistribution of carnitine among tissues or due to a decrease in urinary excretion. In view of previous observations that thyroid hormones increase the hepatic concentrations of carnitine, and clofibrate treatment causes a hyperthyroid state in the liver, we investigated the effect of clofibrate in thyroidectomized rats. Clofibrate treatment of thyroidectomized rats also increased the concentration of free (423 +/- 25 vs. 1,460 +/- 123) and acylcarnitine (35 +/- 6 vs. 305 +/- 31) in the liver. Finally, clofibrate treatment significantly increased the urinary excretion of trimethyllysine, a precursor of carnitine (31 +/- 3 vs. 47 +/- 4 nmol/mg creatinine, mean +/- SE, 5 rats). Our data suggest that clofibrate treatment stimulates hepatic synthesis of carnitine by increasing the availability of its precursor, trimethyllysine. This effect of clofibrate is independent of thyroid hormone. PMID- 3092679 TI - Effect of insulin on uptake of metabolic substrates by the sheep fetus. AB - To measure the effect of fetal hyperinsulinemia on fetal oxidative metabolic rate and the uptake of fetal oxidative substrates, we operated on 12 near-term ewes under spinal anesthesia and placed catheters in the fetus under local anesthesia. Four days after surgery, we began an 18-h insulin infusion, at the end of which we drew blood samples for analysis of oxygen, glucose, lactate, amino-nitrogen concentrations, blood gases, pH, hematocrit, and plasma insulin concentrations, then injected radiolabeled microspheres to measure umbilical blood flow. Three to five infusions were given to each fetus. Fetal plasma insulin concentrations varied from 0.3 to 60 microU/ml. As fetal plasma insulin concentration rose, the blood concentrations of oxygen, glucose, lactate, and amino-nitrogen fell, but the fetal uptakes of oxygen, glucose, and amino-nitrogen rose. The rise of fetal oxygen uptake occurred by increasing oxygen extraction, resulting in arterial hypoxemia. The increase of the glucose uptake was sufficient to account for an increased fraction of oxidative metabolism, allowing the increased uptake of amino acids to be used for either synthetic or oxidative purposes. PMID- 3092682 TI - Prevalence of psychosis, delusions, and hallucinations in clinical trials with bupropion. PMID- 3092680 TI - Effects of 2-tetradecylglycidic acid on myocardial function in swine hearts. AB - Fatty acids in excess impair myocardial function in intact hearts both during aerobic and ischemic blood flow. The purpose of these studies was to determine whether decreases in acylcarnitine, effected by 2-tetradecylglycidic acid (TDGA), would result in the preservation of myocardial function in intact hearts during fatty acid excess. Two groups of intact working swine hearts in which serum fatty acids were augmented three- to fourfold were perfused extracorporeally with whole blood and compared over 90 min. Labeled [U-14C]palmitate was administered selectively into the left anterior descending coronary circulation to follow fatty acid oxidation, and regional myocardial function was assessed with ultrasonic crystals. Coronary flow in this bed was decreased by 50% over the final 30 min of perfusion. Treated swine (n = 10) were compared with a placebo treated control group (n = 9). At similar levels of aerobic flow, TDGA effected a marked decrease in 14CO2 production during 60 min of aerobic perfusion, but levels were similar during the final 30 min of ischemia. Tissue levels of acylcarnitine were significantly reduced and acetyl-CoA levels significantly increased in TDGA-treated hearts both in aerobic and ischemic myocardium. This inhibition of fatty acid metabolism during aerobic flow was associated with an increase in regional myocardial shortening in the treated group. This occurred at similar levels of O2 consumption, evidencing enhanced carbohydrate substrate utilization. During the first 30 min of ischemia 14CO2 production and mechanical function were compromised similarly, whereas lactate production was 70% less (P less than 0.025) in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092681 TI - Effects of lithium carbonate on associative productivity and idiosyncrasy in bipolar outpatients. AB - To determine the effect of lithium carbonate on the productivity and idiosyncrasy of written associations of euthymic outpatients with affective disorder, the authors assessed 22 patients at weekly intervals during lithium treatment, 2 consecutive weeks of placebo, and 2 consecutive weeks after lithium was resumed. Lithium discontinuation produced a significant increase in associational productivity and a demonstrable increase in associative idiosyncrasy, and restoration of lithium dose significantly reversed both effects. The results suggest that lithium may affect the underlying neuropsychological functions critical to the ability to generate associations and indicate the need for further study of lithium's effects on these and other functions that may relate to neuropsychological and creative processes. PMID- 3092683 TI - Uromodulin: an immunoregulatory glycoprotein isolated from pregnancy urine that binds to and regulates the activity of interleukin 1. AB - Uromodulin is an 85 kilodalton glycoprotein originally isolated from human pregnancy which has been shown to inhibit antigen specific T cell responses to recall antigens such as tetanus toxoid. We have also found that uromodulin is a high affinity ligand for interleukin 1 and is able to regulate the activity of interleukin 1 in vitro. Finally, we present data that free interleukin 2 receptor can be found in human pregnancy urine. We propose that a number of immunoregulatory phenomena associated with pregnancy are due to molecules able to specifically regulate interleukin 1 and interleukin 2. PMID- 3092684 TI - Torque developed at simulated sliding between sport shoes and an artificial turf. AB - Rotation torque is known to be one of many factors affecting the risk of injury in athletics. Experiments were performed to examine the torque and friction on different sport shoes when sliding on an artificial turf. An apparatus was constructed in which it is possible to measure simultaneously the torque and the frictional force developed when a shoe slides on a surface. Measurements were made for 25 different shoes on an artificial turf. The frictional force was independent of the speed in the range 1 to 5 m/s. The torque was dependent on the physical distribution of the texture of the sole and slightly dependent on the frictional force. The results indicate that the physical distribution of the sole at the heel and toe, as well as the material, is of great importance for the torque developed. PMID- 3092685 TI - [Light and electron microscopy studies of experimental oral precancerous lesions- DMBA application and wounding]. PMID- 3092686 TI - Carbon dioxide laser stapedotomy: a histopathologic study. AB - The effect of carbon dioxide electromagnetic radiation on biological tissues is thermal. The heat generated from vaporization dissipates into the surrounding tissues and can produce alterations of structure and function. Carbon dioxide laser fenestrations were performed in the footplates of 11 cat ears. Morphologic changes included discoloration and reactive hemorrhage in the saccular wall and disruption of the saccular and utricular walls. The clinical consequences of these findings and the role of the carbon dioxide laser in laser stapedotomies for patients with otospongiosis remain unresolved. PMID- 3092687 TI - Comparison of bacteria in the tympanic cavity and the mastoid antrum in chronic otitis media. AB - Materials collected from the tympanic cavity before operation and from the mastoid antrum during operation of 58 discharging ears of patients with chronic otitis media were cultured, and the bacteria in these two cavities were compared. Staphylococcus aureus was the commonest organism in the tympanic cavity, and S epidermidis in the mastoid antrum. Anaerobic bacteria were found only in the mastoid antrum of patient with cholesteatoma. In 32 (55 per cent) of the 58 ears examined, bacteria were detected in both the tympanic and mastoid cavities. In 17 ears (53 per cent), the bacterial strains in the two cavities differed. The results indicate the necessity of bacteriologic examination of the mastoid cavity during operation to select antibiotics for postoperative treatment. PMID- 3092688 TI - [Lecithin/sphingomyelin in the amniotic fluid in Rh isoimmunization pregnancy and diabetes]. PMID- 3092689 TI - Nebulised sodium cromoglycate in the treatment of wheezy bronchitis. A multicentre double-blind placebo controlled study. AB - The efficacy of nebulised sodium cromoglycate (SCG) used as a prophylactic treatment of wheezy bronchitis in children aged 1 to 4 years was evaluated in a multicentre double-blind placebo controlled, group comparative study. Fifty-four patients completed the 10-week trial (29 treated with SCG and 25 treated with placebo), preceded by 4-8 weeks baseline. Nebulised SCG did not prove significantly superior to placebo in reducing day wheezing, day coughing, or sleep disturbance due to wheezing or coughing at night. Neither was there significant difference in the use of supportive medicine (beta 2-agonist and theophylline) between the groups. Extra doctor visits, hospital admissions, and parental preference did not show significant difference either. PMID- 3092690 TI - [Respiratory minute volumes following end expiratory CO2 values in artificial respiration in anesthesia]. AB - During artificial ventilation of anaesthetised patients the respiratory minute volumes were estimated after end tidal CO2-values (eeCO2) and correlated to arterial blood gases. In men the mean respiratory minute volume of 130 ml/kg body weight (b.w.) was significantly above the 113 ml/kg b.w. of women. 9.7-year-old boys and 16-year-old men had higher minute volumes (178 ml/kg b.w. and 148 ml/kg b.w. respectively) in comparison to men of 23 years of age. In contrast, no significant difference was seen in the older age groups. Overweight men had a significant lower respiratory minute volume (114 ml/kg b.w.), as compared to normal body weight (128 ml/kg b.w.), but overweight women had no significantly different minute volumes compared to normal body weight. During the course of anaesthesia for vaginal hysterectomy the respiratory minute volume had to be reduced in the first and second hour as compared to controls before the start of operation, in order to avoid excessive hyperventilation. EeCO2-values of 3.8 to 4.2 per cent by volume stand for a very marked hyperventilation in the pulmonary healthy patient. The arterial alveolar difference of the CO2 pressure (aADCO2) was in the normal range between 1 and 5 mmHg. The end tidal CO2 estimation is a noninvasive and suitable method to exactly meet the ventilatory needs of the anaesthetised patient. PMID- 3092691 TI - [Intraoperative monitoring in artificial respiration of premature and newborn infants. I. Monitoring of respiratory parameters and alveolar ventilation]. AB - Monitoring of ventilation serves to ensure adequate alveolar ventilation and arterial oxygenation, and to avoid pulmonary damage due to mechanical ventilation. Basic clinical monitoring, i.e., inspection, auscultation (including precordial or oesophageal stethoscope) and monitoring of heart rate and blood pressure, is mandatory. Mechanical ventilation is monitored by ventilation pressures (peak pressure, plateau pressure and endexpiratory pressure), ventilation volumes (measured at the in/expiratory valve of the respirator and by hot-wire anemometry at the tube connector), ventilation rate, and inspiratory oxygen concentration (FiO2). Alveolar ventilation should be continuously and indirectly recorded by capnometry (pECO2) and by measurement of transcutaneous pCO2 (tcpCO2), whereas oxygenation is determined via measurement of transcutaneous pO2 (tcpO2). Invasive monitoring of gas exchange is essential in prolonged or intrathoracic interventions as well as in neonates with cardiopulmonary problems. paCO2 may be estimated by capillary or venous blood gas analysis; arterial blood gas analysis is required for exact determination of paCO2 as well as arteriocutaneous pCO2 (atcDCO2) and arterio-end-expiratory (aEDCO2) gradients. PMID- 3092692 TI - [Changes in total acid-base equilibrium following administration of carbonic anhydrase inhibitor. Experimental studies in the nephrectomized rat in vivo]. AB - We investigated the influence of 50, 200 and 500 mg per kg body weight acetazolamide on the whole-body acid-base status of nephrectomised Sprague-Dawley rats. Intracellular pH (pHi) of liver, brain, heart and two skeletal muscle groups was determined from the distribution of 14C-labelled DMO (5.5.dimethyl-2.4 oxazolidinedione). It was found that compared to a control group an increasing extracellular acidosis was followed by a similar disturbance in liver, brain, and heart, respectively. A significant decrease of pHi in skeletal muscle was found only in severe acidosis. Whereas the bicarbonate concentration in the extracellular compartment, liver, brain, and heart decreased with increasing acidosis, it increased in the two investigated skeletal muscle groups. The results led to the assumption that acetazolamide may be used successfully in treating severe metabolic alkalosis, although further experimental and clinical research appears necessary. PMID- 3092693 TI - [Thiopental distribution in the blood of surgical patients]. AB - The influence of hematocrit, of the concentration of plasma proteins, and of CO2 pressure on the distribution of thiopental in the blood was studied in vitro in 30 venous blood samples. Thiopental was bound to plasma proteins to 80.3-89.2%, mean 85.0%, at a plasma protein concentration of 60 g/l and a pH of 7.37. Considerable changes in the plasma protein concentration had a considerable influence on the binding rate. By halving the protein concentration the free fraction was almost doubled. Increasing the protein concentration to 90 g/l led to binding rates of around 88-89%. When the pCO2 was increased from 40 to 60 torr protein binding decreased slightly, indicating that this barbiturate is mainly bound in its anionic form. At a hematocrit of just under 40 vol.%, 14-34% of the thiopental was absorbed by the erythrocytes. Changes in the plasma protein binding rate influenced the thiopental proportion of erythrocytes, as changes in the hematocrit influenced the plasma thiopental proportion. The concentration of liposoluble thiopental acid physically dissolved in the plasma fluid, just under 8% of the thiopental in the blood, changed relatively little on variation of the hematocrit and the CO2 pressure, thanks to the compensatory function of the plasma proteins and erythrocytes. Since most of the thiopental in the blood is bound to plasma proteins, changes in the protein concentration had the greatest effect on the proportion of thiopental acid of the barbiturate content of the blood. PMID- 3092694 TI - [Airway pressure and transcutaneous O2 and CO2 partial pressure as monitoring measurements for high-frequency jet ventilation?]. AB - Two different methods of measuring airway pressures (n = 7), and the usefulness of transcutaneous pO2 and pCO2 measurement (n = 9) in monitoring High Frequency Jet Ventilation (HFJV), were investigated in critically ill patients. Airway pressures obtained by tip manometer from different points within trachea and mainstem bronchi during HFJV (f = 100/min, inspiratory time 40%, FIO2 0,4, minute volume 25.6 +/- 5.2 l) were nearly identical with pressures obtained from the integrated pressure line of HI-LO-JET endotracheal tubes (R = 0.9638). There was no difference between proximal and peripheral airway pressures. When using a PEEP valve, rather high values of PEEP may occur due to gas trapping. There was sufficient correlation between transcutaneous and arterial pO2 (R = 0.7573) and poor correlation between transcutaneous and arterial pCO2 (R = 0.4987). paO2 values were 51.1% above, paCO2 values 33.4% below transcutaneous values. Transcutaneous measurement of pO2 and pCO2 is only an additional method in monitoring HFJV which can reveal rough trends but cannot replace blood gas analysis. PMID- 3092695 TI - Arterial to end tidal carbon dioxide tension difference during caesarean section anaesthesia. AB - The relationship between arterial carbon dioxide tension and end tidal carbon dioxide tension was studied in 19 patients during general anaesthesia for Caesarean section. Thirteen patients scheduled for elective abdominal hysterectomy formed a nonpregnant group. There was significant correlation between arterial and end tidal CO2 tensions in both groups. During Caesarean section, this difference was significantly less than in the nonpregnant group. PMID- 3092697 TI - [Measurement of end-expiratory carbon dioxide values in pediatric anesthesia]. AB - This study dealt with two principles of the evaluation of end-expiratory CO2 in pediatric anaesthesia: detection of CO2-influenced infrared rays with a full stream analyzer attached to the tracheal tube; CO2 measurement with a side-stream analyzer connected to the breathing and ventilating system by a small tube. The linearity of the analyzers was tested with gas mixtures containing 3.0/5.0/7.0 vol% of CO2 cycling at an increasing rate. Additional mass-spectrometry has proven that the instruments are accurate within the clinical range of pediatric anesthesia. A maximal deviation of 8% develops when cycling rates increase to 40 per min. To detect quality differences in the analyzers, tangential constructions onto the CO2 curves plotted by the capnographs provided valuable quotients. Depending on the length of the tubing that feeds samples of respiratory gas into the side-stream analyzer, the CO2 curves were subject to sinus degradation with increasing respiratory rates. Capnography with full-stream analyzers depended on inspiratory zero CO2 content for reference purposes. PMID- 3092696 TI - [Isoflurane in pediatric anesthesia]. AB - Seventy patients 1-10 years of age were submitted to isoflurane (I) or halothane (H) anaesthesia (O2:N2O = 1:3); H was used as a reference substance. Under I anaesthesia, haemodynamic parameters proved to be well preserved. While the pulse rate under I increased significantly, the diastolic pressure decreased as a result of peripheral vascular dilatation. Baroceptor reflexes seemed to function more properly under the effect of I. Spontaneous respiration was definitely depressed by I. Respiratory rate, minute volume, end-expiratory CO2 and pCO2 values indicated CO2 accumulation. Younger children breathing spontaneously were subject to airway problems in I more than in H anaesthesia by decreasing negative occlusion pressures. Increasing doses of vecuronium bromide (5, 10, 15 and 70 micrograms/kg body wt.) accomplished muscular relaxation of various degrees, as tested by the train-of-four (TOF) method. The use of I in two age groups resulted in faster onset, more profound muscular relaxation, and longer duration in comparison with H; these results were statistically significant. PMID- 3092698 TI - [The influence and effectiveness of hydrochloric acid infusion on the extra- and intracellular acid-base status in vivo. Experimental study on rat tissue]. AB - The influence of HCl infusion on extra- and intracellular acid-base status of liver, brain, heart, and skeletal muscle of nephrectomized rats was investigated in vivo. The present results showed that a decrease of extracellular plasma pH was followed by similar changes of the intracellular pH of the investigated tissues and a loss of bicarbonate from extracellular and intracellular body compartment. The results lead to the conclusion that HCl seems to be a suitable agent for correction of severe metabolic alkalosis. PMID- 3092700 TI - Clinical applications of mechanical ventilation. AB - This paper reviews recent applications of mechanical ventilation such as controlled hypoventilation in acute asthma, domiciliary nocturnal ventilation in chronic respiratory failure due to neuromuscular disease and improvement of left ventricular performance by raised intrathoracic pressure. Established uses of mechanical ventilation include control of respiratory failure, intracranial pressure and pulmonary hypertension while other uses such as internal splinting of flail chest, simultaneous ventilation-compression cardiopulmonary resuscitation and prophylactic postoperative ventilation are more controversial. PMID- 3092699 TI - [Nalbuphine and tramadol for the control of postoperative pain in children]. AB - The postoperative treatment of pain in children is often inadequate: Periphal acting analgetics are not sufficient, opioids are believed to be dangerous because of their respiratory depression. Nalbuphine and tramadol are two narcotics with only a few side effects. The aim of this trial was to investigate the efficacy and safety of these drugs in postoperative pain therapy in children aged 1-9 years. 30 children in each group received in a double-blind and randomized manner either 0.15-0.2 mg/kg nalbuphine or 0.75-1.0 mg/kg tramadol im. Pain intensity and sleep-awake behaviour were documented by a visual analogue scale for 24 h. After 1 h 70% of the patients in both groups had no pain and were sleeping. There was no change in heart rate and systolic blood pressure. Only the diastolic blood pressure decreased as did the respiratory rate, while the tcpCO2 estimated in some patients remained constant. Narcotic reinjections were necessary three times in the nalbuphine group and four times in the tramadol group. Typical opioid side effects were found to be equal in both groups. PMID- 3092702 TI - Diazepam depresses the ventilatory response to carbon dioxide. PMID- 3092701 TI - Testicular function and fertility in men with homozygous alpha-1 antitrypsin deficiency. AB - Fertility and testicular function were studied in eight men with severe homozygous (Pi ZZ variant genotype) alpha-1 antitrypsin (AAT) deficiency. Age- and marital duration standardized fertility, clinical androgenic features, mean testicular volume, plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and semen analysis were all normal apart from a reduction in semen volume. Mean plasma total and free testosterone were elevated and the percentage free testosterone reduced compared with age-matched, healthy fertile controls indicative of increased sex-hormone binding globulin (SHBG) levels representing an early marker for subclinical hepatic dysfunction associated with AAT deficiency. In view of the preservation of normal fertility and testicular function despite chronic respiratory disease and premature death with deleterious AAT gene variants, it is proposed that the high prevalence of genetic polymorphism in the AAT protein may be maintained by the chronological asynchrony of the periods of maximal male reproductive activity (40 years) and the late onset (greater than 40 years) of symptoms in severe AAT deficiency rather than by any balance between reduced reproductive fitness of homozygotes and heterozygote advantage. PMID- 3092703 TI - Crying-induced bronchospasm in childhood asthma: response to nebulized metaproterenol 5% and sodium cromoglycate 1%. AB - Five asthmatic children (2 to 5 years) with persistent crying-induced bronchospasm refractory to concomitant oral theophylline and metaproterenol for 4 weeks were selected for an 8-week uncontrolled study with nebulized metaproterenol 5% and sodium cromoglycate 1%. All five patients had reduction in both crying and non-crying-related asthma. Three patients had reduction in crying behavior. Nebulized metaproterenol and sodium cromoglycate may be effective in treating crying-induced bronchospasm refractory to oral bronchodilators. PMID- 3092704 TI - [Separation of lipoproteins as a function of their apolipoprotein composition. Clinical applications]. PMID- 3092705 TI - Arterial blood gases before, during, and after nitrous oxide:oxygen administration. AB - The use of nitrous oxide as an anesthetic or analgesic agent frequently raises concerns about the possibility of post-inhalational diffusion hypoxemia. We undertook a study in 20 healthy volunteers to determine whether hypoxemia occurs after the self-administration by face mask of a 50:50 mixture of nitrous oxide and oxygen for 15 minutes, followed by breathing room air. Blood gases were measured through an in-dwelling arterial cannula before, during, and after inhalation of the mixture, at time O, five, ten, and 15 minutes, and then 30 seconds, 45 seconds, 2 1/2 minutes, five, and ten minutes following room air breathing. Ten of the 20 subjects breathed a control gas, a mixture of 50% nitrogen: 50% oxygen. No subject demonstrated arterial hypoxemia at any time before, during, or after self-administration of the gas mixture. In the ten subjects who self-administered the control gas there were no significant differences in the PaO2 values while they breathed either gas at any corresponding sampling time. We conclude that diffusion hypoxia is not seen in normal subjects following self-administration of a mixture of 50:50 nitrous oxide and oxygen. PMID- 3092706 TI - Evaluation of decoquinate, lasalocid, and monensin against experimentally induced sarcocystosis in calves. AB - Effects of decoquinate, lasalocid, and monensin against experimentally induced sarcocystosis (Sarcocystis bovicanis) were evaluated in 12 calves, 3 of which were inoculated, nontreated controls. Three additional calves were noninoculated, nontreated controls. Drugs were administered in the feed (33 mg/kg of feed) of the treated calves (3 calves/group) for 87 days. Eight of the 12 inoculated calves died from acute sarcocystosis during the experiment (the 3 inoculated, nontreated controls, the 3 calves given decoquinate, and 2 of the 3 calves given lasalocid). Large numbers of sarcocysts were found in tissues from inoculated calves that survived in the experiment (1 of the 3 calves given lasalocid and the 3 calves given monensin). Although large numbers of sarcocysts developed in the muscles of monensin-treated calves, monensin may have an ameliorating effect on acute sarcocystosis. PMID- 3092707 TI - Clinical and pathologic changes in acute bovine aflatoxicosis: rumen motility and tissue and fluid concentrations of aflatoxins B1 and M1. AB - Effects of aflatoxin on bovine rumen motility were determined by radiotelemetric techniques. Aflatoxin altered amplitude and/or frequency of rumen contractions in steers given dosages of 0.2, 0.4, 0.6, or 0.8 mg of aflatoxin/kg of body weight. Effects of aflatoxin on rumen motility were dose dependent. An increase in elimination time of aflatoxin from rumen contents was observed in steers given the aflatoxin dosages of 0.4 to 0.8 mg/kg. The increase in elimination time of this toxin facilitates diagnostic capabilities for detecting bovine aflatoxicosis by obtaining rumen contents for analysis for aflatoxin. Aflatoxin M1 was detected in rumen contents from steers at 2 hours after aflatoxin was administered. Thus, intraruminal metabolism of aflatoxin B1 to M1 may occur. PMID- 3092709 TI - Determinants of response to eucapneic hyperventilation with cold air in a population-based study. AB - A population-based, epidemiologic investigation conducted in children, adolescents, and young adults analyzed the response to eucapneic hyperventilation with cold air as a continuous variable to better define factors that influence the expression of bronchial responsiveness. Among respiratory illness/symptom variables, only the report of asthma or persistent wheeze in the previous year and the report of a respiratory illness that led to activity restriction were significantly associated with response to cold air. Furthermore, a low, prechallenge FEF/FVC ratio was a significant predictor of response, especially among those subjects who reported a respiratory illness that led to activity restriction. This relationship was not observed for a low prechallenge FEF. PMID- 3092710 TI - [Hepato-biliary dysfunction caused by total parenteral nutrition in a low weight newborn infant]. PMID- 3092708 TI - Primary drug-resistant tuberculosis in children. Emergence of primary drug resistant strains of M. tuberculosis to rifampin. AB - A prospective study of primary drug-resistant strains of Mycobacterium tuberculosis among children was begun at the Kings County Hospital Medical Center of Brooklyn in 1961 and reported at 5 4-yr periods through 1980. The present report extends our observations of primary drug-resistant tuberculosis in children through 1984. The salient finding in the present report was the increase in primary drug resistance to rifampin, 3 of 19 strains resistant in the last period of study (1981 to 1984) as compared with 1 of 96 strains isolated in the previous 3 periods of study (1969 to 1980). This increase was significant (p less than 0.02) even though the number of strains isolated was small. There were continued low resistance rates to ethambutol and para-aminosalicylic acid and stable resistance rates for isoniazid and streptomycin. PMID- 3092711 TI - Transdermal nitroglycerin patches in angina pectoris. Dose titration, duration of effect, and rapid tolerance. AB - The duration of effect of transdermal nitroglycerin patches was studied in 14 patients with angina pectoris. By titrating the dose to achieve specific circulatory effects, we chose a patch size that produced a consistent fall in systolic blood pressure of 10 mm Hg or greater for each patient (10 cm2 in 7 patients, 20 cm2 in 5, and 40 cm2 in 2; releasing 5, 10, and 20 mg of nitroglycerin per 24 hours, respectively). The effects of these individualized patches were compared with those of placebo patches. Compared with placebo, nitroglycerin patches increased exercise duration to the onset of angina (257 +/- 72 compared with 383 +/- 130 seconds, p less than 0.0001) and total exercise time (338 +/- 89 compared with 456 +/- 119 seconds, p less than 0.0001) and decreased ST segment depression (1.0 +/- 0.5 compared with 0.6 +/- 0.4 mm, p less than 0.05) at 4 hours but not at 24 and 48 hours. We conclude that nitroglycerin patches do not show objective evidence of antianginal or antiischemic effects for 24 hours. Tolerance to the circulatory and antianginal effects probably develops within 24 hours of patch application. PMID- 3092712 TI - Auranofin or D-penicillamine in the treatment of rheumatoid arthritis. AB - Ninety patients were entered into a randomized, controlled, double-blind trial lasting 12 months to compare auranofin (6 mg/d), and D-penicillamine (250 mg/d for 4 weeks, 500 mg/d for 4 weeks, then 750 mg/d thereafter) in the treatment of rheumatoid arthritis. Most patients in both groups completed the trial with significant improvement in all quantitative measures of efficacy. Patients treated with D-penicillamine were more likely to have "important improvement" in physician global assessment, swollen joint count, and score and grip strength. The overall frequency of side effects was similar between the two groups; however, more patients were withdrawn for adverse effects from the D penicillamine group, and proteinuria (greater than or equal to 2+) and thrombocytopenia (less than 100 000 mm3) occurred significantly more frequently with D-penicillamine than auranofin (p = 0.028). These results suggest that in the dosage regimen used, auranofin is safer than D-penicillamine but that D penicillamine tends to show greater clinical effectiveness in patients with rheumatoid arthritis. PMID- 3092713 TI - International units for tissue plasminogen activator. PMID- 3092714 TI - Proposed symbols for factor VIII and von Willebrand factor. PMID- 3092715 TI - [Heterogeneity of tubulins of parasitic protozoa]. PMID- 3092716 TI - New technologies and classical parasitology: the use of monoclonal antibodies to identify parasites inside the vectors. PMID- 3092717 TI - [Another case of schistosomiasis from Africa]. PMID- 3092719 TI - [The general review on Fabry's disease]. PMID- 3092718 TI - Sandfly control perspectives. PMID- 3092720 TI - Multiple and large non-ossifying fibromas in children with neurofibromatosis. PMID- 3092721 TI - Cost-effectiveness and risk associated with infants' hip dysplasia screening in France. PMID- 3092722 TI - A preliminary survey on aflatoxin exposure in Singapore. AB - Aflatoxins (naturally occurring chemicals of fungal origin) are powerful liver carcinogens, and increased incidence of hepatocellular carcinoma has been observed in areas where exposure to this mycotoxin is high (e.g., Africa, China). These areas also have a high incidence of HBV infection. It has been suggested that this environmental carcinogen interact with HBV in the aetiogenesis of hepatocellular carcinoma in these areas. The aim of this study was to determine the level of aflatoxin exposure in the local population. Fifty healthy adults were studied. Details of dinner taken the previous evening were obtained. Early morning urine was collected and aflatoxin quantitated by ELISA following purification on an antibody affinity column. Rabbit polyclonal antibody to aflatoxin B1 was used, and the mean of at least two assays were determined. Six individuals (12%) showed ELISA inhibition values of more than 25%, equivalent to aflatoxin levels of more than 100 pg/ml in urine. Levels ranged from 185 pg/ml to 2300 pg/ml aflatoxin B1 equivalents. All 6 individuals consumed fried food. The highest level was found in a medical student who had 'satay' (crushed peanut) sauce with dinner. This is in contrast to 52% individuals from Gambia with urine aflatoxin levels between 100 and 1000 pg/ml. PMID- 3092723 TI - Guanase activity in the donor serum and the incidence of posttransfusion hepatitis non-A, non-B. AB - Guanase activity in sera obtained from various liver diseases and normal subjects was measured by a direct colorimetric method. It was also measured in fresh whole blood (FWB) and fresh frozen plasma (FFP) which were transfused to 78 patients during cardiac operations. Guanase activity was elevated in various liver diseases, and good correlation was found between guanase activity and amino transferases. Thus, guanase activity was thought to be a good marker of liver damage. Among 78 patients, 17 patients (21.8%) developed posttransfusion hepatitis. All were non-A, non-B hepatitis. Mean value of guanase activity in 1527 units of FWB was 1.96 +/- 1.31 U/L, and in 353 units of FFP it was 2.29 +/- 1.02 U/L. Therefore, the normal upper limit of guanase activity of FWB and FFP was defined as 4.5 U/L (mean +/- 2S.D.). Among 1880 units of FWB and FFP, 56 units (3.0%) exceeded this limit. Among 24 recipients of FWB or FFP with guanase activity above 4.5 U/L, 11 cases (45.7%) developed posttransfusion hepatitis, while in 54 recipients of FWB or FFP below 4.5 U/L, only 6 cases (11.1%) developed hepatitis. This result means that blood or plasma with guanase activity above 4.5 U/L had higher risk of transmitting posttransfusion hepatitis non-A, non-B. Accordingly, a screening of donor blood by the activity of guanase may be useful for the prevention of posttransfusion hepatitis non-A, non-B. PMID- 3092724 TI - Clinical experience in the use of clavulanic acid/penicillin regimens in the treatment of uncomplicated gonorrhoea. AB - In an attempt to investigate the possibility of re-establishing the use of penicillins in the treatment of gonorrhoea in Singapore, a series of studies were conducted between 1981 and 1984, to evaluate the efficacy of a variety of penicillin-clavulanic acid combinations. A total of 6 different regimens were evaluated, and we concluded that 3 regimens consisting of 2 doses of Augmentin 3.25 g P.O., 4 hours apart (regimen C), aqueous procaine penicillin G (APPG) 4.5 mega units I.M. + Augmentin 375 mg + probenecid 1g P.O. (regimen E), and APPG 4.5 mega units I.M. + Augmentin 750 mg + probenecid 1g P.O. (regimen F) were very efficacious against infection due to PPNG and non PPNG. The cure rates obtained were 96.6% (regimens C and E), and 95% (regimen F) for infection due to PPNG and 95.6% (regimen C), and 100% (regimens E and F) for those due to non PPNG. Regimen E consisting of aqueous procaine penicillin G 4.5 meg units I.M. + Augmentin 375 mg + probenecid 1g P.O. was felt to be economical as well as effective against PPNG and non PPNG, and had the potential advantage of being effective against incubating syphillis. Regimen consisting 2 oral doses of Augmentin 3.25 g, 4 hours apart was an effective therapy for patients who preferred oral medication alone. However, this therapy was most costly. No serious side effects of treatment were observed with any of the regimens used. PMID- 3092725 TI - The effect of human IgC lambda fragments on gene expression in transfected mouse fibroblasts. AB - We have determined the effect of fragments of the human IgC lambda region on the expression of a linked marker gene on transfection into heterologous LATK cells. No Ig fragment stimulated high expression of the bacterial chloramphenicol acetyl transferase gene under conditions where high activation by the Moloney MSV enhancer was observed. This suggests that there is not an element in this DNA fragment which behaves as a strong enhancer in fibroblast cells. Sequences localised within a 0.9 kb fragment 3' to the Ke-Oz- constant region gene showed low (four fold) stimulation of CAT activity. These results are discussed in relation to measuring gene activity by protein expression assays. PMID- 3092727 TI - Amyloid plaques in Creutzfeldt-Jakob disease stain with prion protein antibodies. AB - Amyloid plaques are found in the brains of some patients with Creutzfeldt-Jakob disease (CJD) and all patients with a related transmissible disorder, Gerstmann Straussler syndrome (GSS). In scrapie, a prion disease of animals, amyloid plaques have been shown to be composed of prion proteins (PrP), which form filaments of relatively uniform diameter. We report here that antisera raised against hamster scrapie PrP specifically stain amyloid plaques in the brains of both humans and rodents with CJD as well as a human subject with GSS. Earlier studies showed that these antibodies react with both rodent and human CJD PrP. The immunostained congophilic amyloid plaques in rodent brains measured 10 to 30 micron in diameter and exhibited a Maltese cross appearance. Limited proteolysis enhanced immunostaining of amyloid plaques in human brain sections from patients with CJD or GSS. Presumably proteolysis increases the exposure of those epitopes shared by human and rodent PrP. The differences in immunoreactivity between rodent and human amyloid plaques are consistent with other findings showing that cellular genes, not infectious purified prions, encode PrP. PMID- 3092726 TI - Granulocytic differentiation induced by retinoic acid in HL-60 cells is associated with changes in adenylate cyclase activity. AB - The effect of all-trans Retinoic Acid (RA) on the activity of membrane bound adenylate cyclase (AC) of human malignant cell lines (HL-60 and U-937) was studied. Granulocytic terminal differentiation of the HL-60 cells was correlated to an increase of AC activity and to a potentiation of guanosine 5' triphosphate (GTP) inhibitory effects on the enzyme activity. No direct in vitro effect of RA on HL-60 membranes was found. Monocytic terminal differentiation obtained on 1 B D arabinofuranosyl cytosine (Ara-C) treated HL-60 cells, or on RA treated U-937 cells, did not modify AC activity. The results here reported suggest relations between the modification of GTP binding protein activity and RA induced granulocytic differentiation of malignant cells. PMID- 3092728 TI - Inhibition of L-[18F]fluorodopa uptake into human brain by amino acids demonstrated by positron emission tomography. AB - The brain uptake of L-[18F]fluorodopa was measured by positron emission tomography in a healthy male volunteer both under fasting conditions and during intravenous amino acid loading. A significant reduction of tracer uptake into the brain was demonstrated with amino acid loading. This finding represents the first direct evidence for competition between L-dopa and other amino acids for uptake across the blood-brain barrier obtained in vivo in a human subject. It underlines the possible importance of interference by dietary amino acids with the therapeutic actions of L-dopa in Parkinson's disease. PMID- 3092729 TI - Serum bactericidal activity and killing rate for volunteers receiving imipenem, imipenem plus amikacin, and ceftazidime plus amikacin against Pseudomonas aeruginosa. AB - Serum bactericidal activity against 20 strains of Pseudomonas aeruginosa was studied in 10 volunteers after administration of imipenem (25 mg/kg), imipenem (25 mg/kg) plus amikacin (7.5 mg/kg), and ceftazidime (25 mg/kg) plus amikacin (7.5 mg/kg). Eight strains were susceptible and 12 were resistant to ticarcillin. Serum levels were measured microbiologically after 30 and 60 min and were, respectively, 97 and 46 micrograms/ml for imipenem given alone and 79 and 45 micrograms/ml for imipenem given with amikacin. Despite the very large dose of imipenem used, imipenem and imipenem plus amikacin appeared slightly less active than ceftazidime plus amikacin (P less than or equal to 0.1; Wilcoxon matched pairs test), with respective median titers at 30 min of 1:128, 1:128, and 1:256 against ticarcillin-susceptible strains and 1:32, 1:32, and 1:64 against ticarcillin-resistant strains; however, more than 90% of the serum determinations, regardless of the regimen, had a serum bactericidal activity greater than or equal to 1:8. Amikacin significantly increased the rate of killing in serum of P. aeruginosa by imipenem. Imipenem plus amikacin appeared as effective as ceftazidime plus amikacin in reducing the viable counts of P. aeruginosa after 24 h of incubation. PMID- 3092730 TI - Polycationic biocides with pendant active groups: molecular weight dependence of antibacterial activity. AB - Two types of polycations with pendant active groups were synthesized: one is polymethacrylate containing pendant biguanide units, and the other is poly(vinylbenzyl ammonium chloride). The two polycations were found to exhibit higher bactericidal activity against Staphylococcus aureus than the corresponding monomers. Fractionation of the polycations was successfully performed on gel filtration chromatography, and examination of the antibacterial activity against S. aureus of the well-characterized polymer samples with various molecular weights (MW) revealed that the activity was strongly dependent on the MW of the polycations and that there existed an optimal MW range for the cidal action of the polymeric biocides. Experiments on the lysis of protoplasts of Bacillus subtilis in contact with the polycations have shown that target sites of the polycationic biocides are cytoplasmic membranes of bacteria. PMID- 3092731 TI - In vitro activity of piperacillin, ticarcillin, and mezlocillin alone and in combination with aminoglycosides against Pseudomonas aeruginosa. AB - A total of 103 isolates of Pseudomonas aeruginosa were studied to compare the in vitro effectiveness of three beta-lactam antibiotics (piperacillin, ticarcillin, and mezlocillin) when used alone and in combination with four aminoglycosides (tobramycin, gentamicin, amikacin, and netilmicin). All drugs were tested as single agents against a standard inoculum (5 X 10(5) CFU/ml). The three antipseudomonal penicillins were also tested against the isolates at a higher inoculum concentration (10(7) CFU/ml). Synergy testing was performed by the two dimensional checkerboard method and was defined by a fractional bactericidal index of less than or equal to 0.5 and bacterial killing accomplished at antibiotic concentrations no greater than those achievable in serum. All combinations were assessed for synergy. The degree of synergy was further analyzed by dividing the isolates into groups based on their susceptibility and resistance to the individual agents in the combination. The overall effectiveness of the various aminoglycoside-antipseudomonal penicillin combinations was assessed regarding their ability to kill the isolates either as single agents or through synergy. Piperacillin was the most active antipseudomonal penicillin, and tobramycin and amikacin were the most active aminoglycosides when used as single agents. When tested against isolates at a higher inoculum concentration, ticarcillin was significantly more active than the other beta-lactams. The highest degree of overall synergy was noted with gentamicin-ticarcillin (78.2% of strains) and amikacin-piperacillin (77% of strains). When assessed for overall effectiveness, all combinations containing amikacin were the most active. The combination of amikacin-piperacillin was the most effective, with activity against 96% of all isolates. PMID- 3092733 TI - Mapping and cloning of Corynebacterium diphtheriae plasmid pNG2 and characterization of its relatedness to plasmids from skin coryneforms. AB - The relationship of plasmid pNG2, isolated from an erythromycin-resistant strain of Corynebacterium diphtheriae, to plasmids isolated from skin coryneforms was examined. The extent of homology between plasmids from erythromycin-resistant and -susceptible skin coryneforms and pNG2 varied, but in aggregate homology was observed with all six BstEII fragments of pNG2. The data support the hypothesis that pNG2 originated in skin coryneforms. Intact plasmid pNG2 and some of its restriction fragments were cloned into Escherichia coli JM109. The erythromycin resistance phenotype was expressed in clones carrying intact pNG2 as well as in some of its fragments and appeared to depend on a C. diphtheriae promoter for expression. A 2.5-megadalton EcoRI fragment, the smallest expressing resistance, contained the 1.2-megadalton region of pNG2 which is deleted when the erythromycin-resistant strain of C. diphtheriae reverts spontaneously to the susceptible state. PMID- 3092732 TI - Discrepancies between disk diffusion and broth susceptibility studies of the activity of ticarcillin plus clavulanic acid against ticarcillin-resistant Pseudomonas aeruginosa. AB - Ticarcillin and clavulanic acid in combination were tested against 40 Pseudomonas aeruginosa isolates resistant to ticarcillin by disk diffusion. A total of 21 isolates (53%) were susceptible to ticarcillin-clavulanate by disk diffusion, under currently recommended criteria for ticarcillin susceptibility. Macro-broth dilution tests (ticarcillin plus clavulanic acid, 2 micrograms/ml) confirmed susceptibility (MIC less than or equal to 64 micrograms/ml) of only 8 (38%) of 21 isolates. Time-kill studies of disk diffusion susceptible isolates indicated 2 log10 or greater killing of most isolates at 6 h in broth containing ticarcillin (64 micrograms/ml) combined with clavulanic acid (1, 2, 5, or 10 micrograms/ml). After 6 h, regrowth was common in all concentrations of clavulanic acid except 10 micrograms/ml. Regrowth populations were resistant to ticarcillin-clavulanate by MIC determination. Poor bactericidal activity of ticarcillin-clavulanate against ticarcillin-resistant P. aeruginosa was confirmed, as most isolates did not undergo 99.9% or greater killing at 24 h in all concentrations of clavulanic acid. Serotype O-11 was our most common serotype and was associated with disk diffusion "pseudosusceptibility." Concomitant disk diffusion testing of ticarcillin-clavulanate and ticarcillin is recommended for testing the susceptibility of P. aeruginosa to ticarcillin-clavulanate by disk diffusion. P. aeruginosa isolates resistant to ticarcillin should as a rule be considered also resistant to ticarcillin-clavulanate, despite apparent susceptibility by disk diffusion. PMID- 3092734 TI - Heterogeneity of plasmids determining high-level resistance to gentamicin in clinical isolates of Streptococcus faecalis. AB - Between November 1981 and October 1984, 48 of 3,458 clinical isolates of Streptococcus faecalis at the University of Michigan Hospital showed high-level (greater than 2,000 micrograms/ml) resistance to gentamicin, as well as to all other clinically available aminoglycosides. Thirteen percent of clinical isolates in the University of Michigan Hospital currently demonstrate this level of resistance. Transfer of resistance to a plasmid-free streptococcal recipient was observed in filter matings for 44 of 48 such isolates. Analysis of transconjugants by agarose gel electrophoresis showed that gentamicin resistance was transferred alone in 8 isolates and was combined with other antimicrobial resistances on the same plasmid in the other 36 isolates. There were seven isolates which transferred the property of horse blood beta-hemolysis along with gentamicin resistance. Transfer of gentamicin resistance was either by conjugative plasmids or by a nonconjugative but mobilizable plasmid. Transfer frequencies on filters ranged from 4.7 X 10(-2) to 4.1 X 10(-8). Based on donor and transconjugant antibiotic resistance markers, agarose gel electrophoresis, transfer properties, and restriction enzyme analysis, the plasmid content of transconjugants was heterogeneous and could be classified into at least seven different patterns. These findings argue against clonal dissemination as the cause of the increased frequency of resistant strains and suggest that resistance to gentamicin appears on a variety of physically distinct conjugative and nonconjugative plasmids in S. faecalis. PMID- 3092736 TI - Rates of dissolution and biodegradation of water-insoluble organic compounds. AB - We conducted a study of the relationship between the dissolution rates of organic compounds that are sparingly soluble in water and the biodegradation of these compounds by mixed cultures of bacteria. The rates of dissolution of naphthalene and 4-chlorobiphenyl were directly related to their surface areas. The bacteria caused a decline in the concentration of the soluble substrate. The rate of bacterial growth fell abruptly when 4-chlorobiphenyl or naphthalene was no longer detectable in solution. The population continued to increase in media with different surface areas of insoluble 4-chlorobiphenyl, but the final counts were higher in media in which the surface areas of the substrate were larger. The rates of dissolution of palmitic acid, octadecane, di(2-ethylhexyl) phthalate, and 1-naphthyl N-methylcarbamate were determined in the absence of microorganisms. A mixed culture of microorganisms mineralized palmitic acid, di(2 ethylhexyl) phthalate, and Sevin (1-naphthyl N-methylcarbamate) at a logarithmic rate, but octadecane mineralization was linear. The rates of mineralization at the end of the active phase of the biodegradation were lower than the rate of dissolution of palmitic acid but higher than the rate of dissolution of octadecane in the uninoculated medium. We suggest that spontaneous dissolution rates are only one of the factors that govern the rates of biodegradation. PMID- 3092735 TI - Development of high-level streptomycin resistance affected by a plasmid in lactic streptococci. AB - Some lactose-negative (Lac-) mutants of Streptococcus lactis C2 and ML3 exhibited development of very high level streptomycin resistance after incubation with subinhibitory concentrations of the drug for 18 to 22 h. These drug-resistant mutants showed no loss of resistance even after 6 months of subculturing in broth without any drug. The parental Lac+ strains did not show mutation to high-level streptomycin resistance. The Lac+ characteristic of the parental strain was conjugally transferred to Lac- derivatives of C2 and ML3, showing the ability to mutate to high-level resistance. When transconjugants were analyzed for this characteristic, they showed both mutable and nonmutable Lac+ types. The results suggested that genetic information for mutation to high-level streptomycin resistance in lactic streptococci resides on the chromosome, and its expression is affected by a plasmid. The plasmid profiles of strains C2, ML3, C2 Lac-, ML3 Lac-, and two kinds of transconjugants confirmed the presence of a plasmid of approximately 5.5 megadaltons in strains showing no mutation to high-level streptomycin resistance, while strains missing such a plasmid exhibited high level streptomycin resistance after incubation with subinhibitory concentrations of the drug. PMID- 3092737 TI - High-efficiency transformation of Streptococcus lactis protoplasts by plasmid DNA. AB - Streptococcus lactis IL1403 protoplasts were transformed by plasmid pIL204 (5.5 kilobases), which conferred erythromycin resistance with an average efficiency of 5 X 10(6) transformants per microgram of supercoiled DNA. The procedure used and transformation efficiencies obtained were close to those described for Bacillus subtilis (G. Chang and S. N. Cohen, Mol. Gen. Genet. 168:111-115, 1979). PMID- 3092738 TI - Prostaglandin H synthase and hydroperoxides: peroxidase reaction and inactivation kinetics. AB - The reaction kinetics of the peroxidase activity of prostaglandin H synthase have been examined with 15-hydroperoxyeicosatetraenoic acid and hydrogen peroxide as substrates and tetramethylphenylenediamine as cosubstrate. The apparent Km and Vmax values for both hydroperoxides were found to increase linearly with the cosubstrate concentration. The overall reaction kinetics could be interpreted in terms of an initial reaction of the synthase with hydroperoxide to form an intermediate equivalent to horseradish peroxidase Compound I, followed by reduction of this intermediate by cosubstrate to regenerate the resting enzyme. The rate constants estimated for the generation of synthase Compound I were 7.1 X 10(7) M-1 s-1 with the lipid hydroperoxide and 9.1 X 10(4) M-1 s-1 with hydrogen peroxide. The rate constants estimated for the rate-determining step in the regeneration of resting enzyme by cosubstrate were 9.2 X 10(6) M-1 s-1 in the case of the reaction with lipid hydroperoxide and 3.5 X 10(6) M-1 s-1 in the case of reaction with hydrogen peroxide. The intrinsic affinities of the synthase peroxidase for substrate (Ks) were estimated to be on the order of 10(-8) M for lipid hydroperoxide and 10(-5) M for hydrogen peroxide. These affinities are quite similar to the reported affinities of the synthase for these hydroperoxides as activators of the cyclooxygenase. The peroxidase activity was found to be progressively inactivated during the peroxidase reaction. The rate of inactivation of the peroxidase was increased by increases in hydroperoxide level, and decreased by increases in peroxidase cosubstrate. The inactivation of the peroxidase appeared to occur by a hydroperoxide-dependent process, originating from synthase Compound I or Compound II. PMID- 3092739 TI - Murine glucocorticoid receptors: new evidence for a discrete receptor influenced by H-2. AB - The glucocorticoid receptor contents in the lungs of females of two congenic strains of mice, B10.A (H-2a) and B10 (H-2b), differing only in the H-2 histocompatibility region of chromosome 17, have been measured by the dextran charcoal method and by our previously described methods of molecular sieving and ion exchange chromatography [M. Katsumata, C. Gupta, and A. S. Goldman (1985) Arch. Biochem. Biophys. 243, 385-395]. As reported, two receptors, II and IB, are demonstrable by each column chromatographic method, and 5,5-diphenylhydantoin binds to receptor IB but not to receptor II. Receptor IB cannot be detected unless molybdate is added in cytosols prepared with hypotonic buffer [10 mM 4-(2 hydroxyethyl)-1-piperazineethanesulfonic acid and 10 mM dithiothreitol, pH 7.35) according to S. L. Liu, J. F. Grippo, R. P. Erickson, and W. B. Pratt (1984) J. Steroid Biochem. 21, 633-637], a method which has been reported to give maximal receptor levels. Using hypotonic buffer containing 10 mM molybdate we observed a small but significantly higher content of receptor IB in B10.A mice than that in B10 mice, but no significant difference in receptor II or total receptor content. On the other hand, cytosols prepared with isotonic buffer (50 mM Tris-HCl, 120 mM NaCl, 1 mM EDTA, 10 mM dithiothreitol, and 10 mM molybdate, a modification of the buffer used in our previous report) contained significantly higher levels of receptor IB and of total binding in pulmonary cytosols of B10.A as compared to those of B10. There was no difference in receptor II content. Molybdate stabilizes receptor IB in both buffers. These results explain the apparent contradiction between our results and those of Liu et al. by showing that the hypotonic buffer used by them allows for determination of maximal levels of receptor II, but permits selective destruction of receptor IB. However, the use of isotonic buffer gives maximal values of both receptors II and IB. With isotonic buffer, it is demonstrated that only the level of receptor IB is influenced by H-2-linked genes. PMID- 3092740 TI - Effects of lysophosphatidylcholine micelle and phosphatidylcholine liposome on photoreduction of methylviologen. AB - Photoinduced reduction of methylviologen (MV2+) by ethylenediaminetetraacetate (EDTA3-), which was sensitized by thiacarbocyanine dyes having long alkyl chains (C+m-n) embedded in palmitoyl lysophosphatidylcholine micelle and dipalmitoyl phosphatidylcholine liposomal membrane, was carried out. The formation rate of reduced methylviologen cation radical (MV+.) decreased with the time of irradiation with visible light, and the deceleration was more pronounced in the micellar solution. In kinetic studies, we found that the sensitizer divalent cation radical (C2+.m-n) is formed through the reaction of photoexcited sensitizer (C+*m-n) with MV2+ as an intermediate in this reaction, and that the reduction of C2+.m-n with EDTA3- inhibits the back reaction of MV+. with C2+.m-n. The inhibition was greater in the liposomal solution than in the micellar solution. This was ascribed to a higher concentration of EDTA3- on the liposomal surfaces through the electrostatic interaction between EDTA3- and the liposomal surfaces, the charge of which is attributed to the univalent cation sensitizer embedded in the liposomal membrane. The difference in the positive charge density of the surface of these lipid aggregates was due to the difference in the curvature of the micelle and the liposome. These results suggest that the dipalmitoyl phosphatidylcholine liposome is a more effective carrier than the palmitoyl lysophosphatidylcholine micelle for the production of MV+. in the photoreduction studied here. PMID- 3092741 TI - The incorporation of a fluorescent probe into the active sites of one- and two chain tissue-type plasminogen activator. AB - Dansyl-glutamyl-glycyl-arginyl chloromethyl ketone (DEGR-CK) was shown to inactivate both one- and two-chain human, recombinant tissue-type plasminogen activator (t-PA). The interaction of DEGR-CK with both forms of t-PA was accompanied by an identical increase in the fluorescence intensity and a blue shift in the wavelength of maximum emission, which suggests that the environment of the incorporated DEGR is similar in both one- and two-chain t-PA. The kinetics of the interaction of t-PA with DEGR-CK could be followed by both loss of activity and increase in fluorescence. The second order rate constants (k2/Ki) obtained with these two methods agreed quite well. With two-chain t-PA the values were 42 X 10(4) M-1 min-1 and 46 X 10(4) M-1 min-1 by the activity loss and fluorescence methods, respectively. With one-chain t-PA the results were 2.5 X 10(4) M-1 min-1 and 3.1 X 10(4) M-1 min-1. The rate at which one-chain t-PA is inactivated by DEGR-CK is 15 times lower than the rate with two-chain t-PA. The results demonstrated, however, that the cleavage of the one-chain protein to the two-chain form is not required for reactivity with DEGR-CK. This fluorescently labeled t-PA should be useful in probing the interactions of one- and two-chain t PA with other proteins. PMID- 3092742 TI - Characterization of cellular oligosaccharides from normal and cystic fibrotic fibroblasts using sequential endoglycosidase digestions. AB - A method was developed for obtaining detailed oligosaccharide profiles from [2 3H]mannose- or [6-3H]fucose-labeled cellular glycoproteins. The oligosaccharides were segregated first according to class, using endo-beta-N-acetylglucosaminidase H (Endo H) to release the high mannose species, and then with peptide-N4-(N acetyl-beta-glucosaminyl)asparagine amidase (PNGase F), which provided a complete array of complex oligosaccharide chains. The high mannose and complex oligosaccharides were fractionated subsequently according to net negative charge on QAE-Sephadex. High resolution gel filtration on TSK HW-40(S) resolved the neutral high mannose population into species of the type Man9-5 N acetylglucosamine. Desialylation of the complex chains with neuraminidase allowed resolution of these oligosaccharides into their corresponding asialo bi-, tri-, and tetraantennary species. Fibroblasts from normal and cystic fibrosis cells were analyzed for differences in their glycosylation patterns using these techniques. Over 95% of the [2-3H]mannose-labeled glycoproteins were susceptible to the combined glycosidase digestions, but no difference in either the high mannose or complex oligosaccharides were observed. Nonetheless, the methodology developed in this study provides an important new approach for investigating oligosaccharides of different cell types and variants of the same type. Metabolic changes induced in cellular glycoproteins, as illustrated by use of the processing inhibitor swainsonine, demonstrated the versatility of this procedure for investigating questions relating to glycoprotein structure and enzyme specificity. Thus, by employing a variation of this method, it was possible to confirm the location of fucose in the core of PNGase F-released hybrid oligosaccharides by the subsequent release with Endo H of the disaccharide, fucosyl-N-acetylglucosamine. PMID- 3092744 TI - The removal of the carboxy-terminal region of tubulin favors its vinblastine induced aggregation into spiral-like structures. AB - Vinblastine induces brain tubulin to assemble into spirals. This process is stimulated by microtubule-associated proteins (MAPs) which copolymerize with brain microtubules assembled in vitro. When the carboxy terminal of tubulin is removed by subtilisin digestion, vinblastine readily induces the aggregation of tubulin into spiral-like or circular structures, even in the absence of MAPs. These results suggest that in the absence of MAPs, the carboxy-terminal domain of tubulin may inhibit vinblastine-induced polymerization of tubulin into spiral like structures. PMID- 3092743 TI - Glycogen metabolism in neonatal liver of the rat. AB - Prior to birth the fetus of the rat accumulates large quantities of hepatic glycogen, with these stores mobilized as glucose in the early postnatal period to sustain the newborn until the onset of suckling and gluconeogenesis. The liver acts to mobilize glycogen in the early neonatal period and gradually adjusts to the alternating supply of nutrients that results from the onset of a feeding cycle. Early postnatal glycogen mobilization is reflected in the decreased active form of glycogen synthase (GS), the rate-limiting enzyme of glycogenesis, and increased activation of glycogen phosphorylase (GP), the rate-limiting enzyme of glycogenolysis. Levels of smooth endoplasmic reticulum (SER)-associated synthase phosphatase and phosphorylase phosphatase activities are diminished from high prenatal levels, contributing to these changes in activation of GS and GP. With the onset of suckling at 1-4 h after birth the liver again accumulates small quantities of glycogen. The period of 6 to 12 h after birth is characterized by large scale glycogenolysis. Glycogen levels are again increased at 24 h after birth, reflecting hepatic adaptation to the onset of meal feeding. PMID- 3092745 TI - Amino acid catabolism by perfused rat hindquarters: degradation of threonine and isoleucine. AB - Rat hindquarters were perfused without added substrate other than trace amounts of [U-14C]threonine or [U-14C]isoleucine. Comparison of incorporation of radiolabel into some nonessential amino acids, citrate cycle intermediates, and lactate is presented. Activities of three enzymes for the initial reactions in threonine degradation are reported. It is concluded that skeletal muscle catabolizes threonine, and that the latter is a potential source of carbon for glucogenic precursors for the liver. In contrast, label from isoleucine was incorporated into glutamate, glutamine, and alanine much more than was that from threonine. Large amounts of organic acids accumulated, and more than 60% of total radioactivity was lost as CO2 during a 2-h perfusion period. PMID- 3092746 TI - [A case of an aged woman with advanced gastric cancer which dramatically responded to combined chemotherapy with UFT and mitomycin C]. AB - An aged female patient with inoperable gastric cancer was treated with a combined chemotherapy using UFT and Mitomycin C. She was diagnosed as having Borrmann type 1 gastric cancer, which was revealed to be well differentiated adenocarcinoma. Both gastrofiberscopy and X-ray pictures showed a reduction in the size of the gastric cancer. As a result of this therapy, partial response (PR) was obtained, and the response was maintained for more than 7 months. PMID- 3092747 TI - [Effects of regional hyperthermia on metastatic carcinoma of the liver]. PMID- 3092748 TI - A 43-kDa papain inhibitor produced by a cultured human epidermal cell line. AB - Epidermis-derived cells (NCTC 2544) were cultured and the proteins of the culture medium, as well as of the cells, were fractionated by gel-chromatography. The fractions were analyzed for their papain-inhibitory capacity and for the presence of so-called 43-kDa papain inhibitor. A papain inhibitor was identified with molecular weight and immunological characteristics similar to the original 43-kDa inhibitor that was isolated from psoriatic scales. The result proves that NCTC 2544 cells can produce the so-called psoriasis inhibitor under culture conditions. PMID- 3092749 TI - Effect of interferons (rIFN-alpha 2, rIFN-gamma) on DNA-synthesis and HLA-DR expression in psoriasis. PMID- 3092750 TI - Concentrations and chromatographic profile of DDT metabolites and polychlorobiphenyl (PCB) residues in stranded beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary, Canada. PMID- 3092751 TI - [Major nutrition problems and practical solutions]. PMID- 3092752 TI - Study of some immunopharmacological properties of praziquantel in experimental schistosomiasis mansoni. AB - The immunopharmacological properties of praziquantel were studied in mice infected with Schistosoma mansoni. Hepatic granuloma measurement was the main parameter of assessment. Delayed foot pad swelling as an in vivo correlate for the delayed granulomatous hypersensitivity reaction was also determined. Fluorescent direct antigen-antibody reaction in the granuloma together with the immediate foot pad swelling were used to test for the humoral immune response. Praziquantel administered at seven weeks after infection in two dose regimens (3 X 250 mg kg-1 for three consecutive days and 3 X 83 mg kg-1 given four hourly within the same day was more or less equally effective in reducing the size of hepatic granuloma by 37-41% two weeks after treatment and by 81-85% one month after treatment. Delayed foot pad swelling using soluble egg antigen (SEA) was significantly suppressed one month after treatment by 53%. At nine weeks after infection the fluorescent antigen-antibody reaction in the granuloma was positive in the untreated controls, but at the same time (i.e. two weeks after treatment) it was negative in the praziquantel-treated mice. One month after treatment positivity was less compared to infected control mice. Reduction in worm burden, hepatic shift of the worms and the reduced number of ova per gram of tissue denoted the efficacy of the drug in its two dose regimens against the Egyptian strain of S. mansoni. PMID- 3092753 TI - The economic implications of infection in cardiac surgery. AB - To assess the economic impact of infection, the records of 496 patients aged 18 to 82 years (mean, 61 years) undergoing open-heart operations in 1981 and 1982 were reviewed, and the costs (length of stay, hospital charges, pharmacy charges) were compared for matched pairs of patients with and without infection who had coronary artery bypass grafting (CABG) procedures. Patients received a 5-day regimen of prophylactic cephalosporin. Operative site infections occurred within 6 months of operation in 17 patients (3.4%), urinary tract infections in 9 (1.8%), and pulmonary infections in 6 (1.2%). Early and late mortality was each 2%. No deaths were infection related, and no postoperative bacterial endocarditis occurred (minimum one-year follow-up). For the matched CABG patient in whom a postoperative wound infection developed, the average length of hospital stay was 16.7 days longer and the average hospital bill was $8,118 greater, with the average cost to the hospital $6,605 greater. PMID- 3092754 TI - Effects of 17 beta-estradiol on the isolated rabbit heart. AB - We have studied the effects of 17 beta-estradiol on the left ventricular pressure and on the coronary perfusion pressure in isolated rabbit heart, in order to evaluate the action of this hormone on the myocardial contractility and on the coronary resistances. 17 beta-Estradiol has induced a negative inotropic effect starting from a concentration of 10(-6) M and a vasodilation starting from 10(-7) M when administered on a vasopressin-induced coronary spasm. These effects are not related to sex or to alpha-, beta-adrenergic, histaminergic, anaesthetic-like mechanisms, but seem to interfere with calcium transport. PMID- 3092755 TI - Comparative antiarrhythmic actions of encainide and its major metabolites. AB - The local anesthetic, antiarrhythmic, and acute toxicologic properties of the O demethyl (ODE), 3-methoxy-O-demethyl (MODE) and N-demethyl (NDE) analogs of encainide (E) were compared with those of parent drug in several models. In the mouse chloroform-induced fibrillation model, the order of antiarrhythmic potency was ODE greater than E greater than MODE greater than NDE. The acute LD50 values for ODE, E, MODE and NDE in mice were 22.6, 38.1, 43.6 and 81.1 mg/kg, i.p. Based upon the toxic/therapeutic ratio in mice, ODE appeared to have the greatest margin of safety and MODE the least; E and NDE were intermediate. In dogs with ouabain-induced tachyarrhythmias, the converting doses of encainide, ODE, MODE and NDE were 0.67, 0.15, 0.39 and 1.1 mg/kg, i.v., respectively. The ODE and MODE metabolites thus appear to be more potent on a mg basis, but both have shorter durations of action than the parent compound. Antiarrhythmic activity in this model was best reflected by plasma drug level (Cp) rather than dose of drug administered. Antiarrhythmic onset Cp associated with encainide (244 ng/ml), ODE (77 ng/ml), MODE (164 ng/ml) and NDE (851 ng/ml) have been identified in this anesthetized dog model. In conscious dogs previously subjected to Harris two stage coronary artery ligation, the minimal effective doses of encainide were 0.5 mg/kg i.v. and 1 mg/kg orally. For ODE and MODE the minimal effective doses were 0.25 and 0.19 mg/kg injected i.v., respectively, and 0.5 and 0.38 mg/kg given orally. By both routes, encainide had the shortest onset, longest duration and most consistent profile of sustained antiarrhythmic effects. Antiarrhythmic activity did not correlate with local anesthetic potency of either encainide or its metabolites. The data are consistent with the hypothesis that the metabolites of encainide may contribute to and/or be responsible, at least in part, for the persistent antiarrhythmic actions observed clinically following chronic administration of the parent drug in patients. PMID- 3092756 TI - New intravascular contrast material. PMID- 3092757 TI - Medical and economic considerations in using a new contrast medium. AB - In deciding to use a new intravascular contrast medium, the considerations should be patient safety, Imaging efficacy, and cost. Balancing these factors, use can be estimated. With the new low-osmolality contrast media, particularly the nonionic media, the expected increased patient safety must be balanced against the much higher cost. PMID- 3092758 TI - Reduced or absent serum anion gap as a marker of severe lithium carbonate intoxication. AB - Two patients with life-threatening lithium carbonate intoxication (serum levels, greater than 4 mEq/L [greater than 4 mmol/L]) presented with a reduced or absent serum anion gap. In both subjects, hemodialysis simultaneously removed the excess lithium ion and normalized the anion gap. Conversely, the anion gap was normal in subjects with therapeutic serum lithium ion levels. Severe lithium carbonate intoxication should be added to the category of illnesses (multiple myeloma, bromide intoxication) causing a marked reduction in the anion gap. In the comatose patient, a reduced anion gap may serve as an important clinical clue to the presence of this drug intoxication. PMID- 3092759 TI - [Fetal cardiology: a new perspective in pediatric cardiology]. PMID- 3092760 TI - [Pediatric cardiology. Pediatric Cardiology Group of the French Society of Cardiology]. PMID- 3092761 TI - [Quantitative echography of the fetal heart]. AB - One hundred and twenty two fetal echocardiograms were performed during normal pregnancies between the 20th and 38th weeks of gestation. Freeze frame M mode and 2D imaging was used to perform the following measurements: right and left systolic and diastolic ventricular dimensions, dimensions of the two atria, aortic and pulmonary artery dimensions, fractional shortening of both ventricles, ratio of right ventricular to left ventricular end diastolic dimensions RVEDD/LVEDD, ratio of pulmonary artery to aortic dimensions PA/Ao. The causes of error or failure were analysed. The results classified by gestational age show progressive growth of all structures which double their size during the second half of the pregnancy; the "physiological" septal hypertrophy reported by some workers was not observed in this series; similarly, paradoxical septal motion was only present in 3% of the fetuses studied. The RVEDD/LVEDD ratio approached unity, which questions the classical but hypothetical concept of physiological right ventricular preponderance, a concept also queried by recent fetal Doppler intracardiac flow studies. The repertory of normal values is particularly useful for the detection of cardiac malformations and for the surveillance of some pregnancies with a high risk of cardiomyopathy, as in maternal diabetes. PMID- 3092762 TI - [Transient myocardial ischemia in newborn infants]. AB - Thirty new born babies with Apgar scores of 5 or less were randomly selected for clinical and electrocardiographic study. Twenty five had electrocardiographic changes of myocardial ischaemia (ST and T wave abnormalities). Generalised low voltage was a common finding (21 cases) whilst pathological Q waves were observed more rarely (5 cases) but did not seem to carry a poor prognosis. Seventeen babies had cardiac clinical signs: isolated tricuspid regurgitation or associated with cardiac failure. Five babies died; autopsy showed subendocardial infarction in all cases. The electrocardiogram of the survivors returned to normal within 15 days in 80% of cases. The authors discuss the physiopathology and demonstrate a clear relationship between neonatal hypoxia and myocardial ischaemia. Attentive clinical examination and systematic electrocardiography in these babies at risk seem to be justified for the detection and treatment of myocardial ischaemia. PMID- 3092763 TI - [Arrhythmia after atrial correction of transposition of the great vessels. Holter recording study of 123 surgically treated patients]. AB - Sinus node dysfunction after intra-atrial repair of transposition of the great arteries by a Mustard or Senning procedure is well known. We undertook this study to evaluate the frequency, the nature, the severity and evolution of these dysrhythmias by performing Holter monitoring in 123 children followed up over 5 years; 302 Holter recordings were reviewed. The patients were divided into 3 groups of increasing severity: I = no sinus node dysfunction, II = moderate sinus node dysfunction, III = severe sinus node dysfunction with bradycardia of less than 30/min and/or pauses of over 2000 ms. The association of atrial hyperexcitability was classified in 3 subgroups: A = no extrasystoles, B = at least 4 extrasystoles per 24 hours, C = atrial tachycardia (focal tachycardia or flutter) after the first six postoperative months. There were only 15% of normal recordings (IA) and the majority of children (58%) were classified in the intermediary groups (IB, IIA and IIB). Sinus node dysfunction tended to become more severe with time in nearly 30% of the 69 cases followed up sequentially. The bradycardia tended to become more severe and associated with episodes of atrial tachycardia: the frequency of type B and C increased to 30% in Group I, to 68% in Group II and to 91% in Group III. The attacks were severe, especially in patients with a mediocre postoperative haemodynamic result. This explains the global mortality of 3%, the morbidity of 15% and the pacemaker implantation rate of 12%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092764 TI - [Congenital subclavian steal syndrome. Apropos of 14 cases. Review of the literature]. AB - Fourteen cases of the congenital subclavian steal syndrome are presented with a review of 99 cases in the literature. This abnormality is usually asymptomatic and a fortuitous finding (clinical: asymmetric blood pressure; radiological: investigation of an associated cardiovascular malformation). The possible malformations are numerous and may be diagnosed by angiography: however, they can be suspected from three simple investigations, clinical examination indicating the side of lower blood pressure, chest X-ray and barium swallow. Seventy one per cent congenital subclavian steal syndromes are associated with a right-sided aortic arch, the steal being then almost always left-sided via a left subclavian artery anomaly. In this group, a left subclavian artery isolated from the aorta represents about a half of the cases. A cardiac malformation is present in one out of two cases and a patent ductus arteriosus uniting the left subclavian artery and the left pulmonary artery is observed in one out of four cases. Twenty nine per cent of congenital subclavian steal syndromes are associated with a left sided aortic arch. In these cases the abnormalities usually involve the aortic arch (57% of cases) or a right or left subclavian artery. Therefore, in this group, there is no preferential side for the subclavian steal which can be right, left or bilateral. These abnormalities usually only require medical surveillance. When they become symptomatic, vertebro-subclavian revascularisation is justified. The presence of a subclavian steal may have surgical implications: it is important to exclude a subclavian steal before performing a Blalock anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092765 TI - [Congenital paravertebral arteriovenous fistulae in children and adolescents]. AB - These arteriovenous fistulae (AVF) situated in the paravertebral area present as a murmur which explains their cardiological orientation. They are characterised by the presence of one or more afferent paravertebral arteries giving rise to collateral vessels irrigating the bone marrow. The aim of this study of 13 cases was to study the diagnostic and therapeutic problems, and the evolution of this particular localisation of AVF. Two groups of paravertebral AVF were individualised: - Cervical AVF in which the vertebral artery was always involved (7 cases). Four were simple (only one fistula) and three were complex, having several afferent arteries. Two presented as a rapidly growing vascular tumour. Two caused an asymptomatic angiographic vertebral steal syndrome. Two simple forms were obturated by a detachable balloon and one by surgical excision. Two complex forms were treated by embolisation and surgery. Total closure of the AVF was obtained in all cases without complications. - Dorso-lumbar AVF (6 cases). The afferent vessels are the intercostal (D6 to D8) or lumbar (L2 to L4) arteries. Anatomically, these are extra-medullary fistulae with an extra or intra vertebral venous drainage. Enlargement in an adjacent conjugating foramen forms a tumour which may narrow the spinal canal (1 case diagnosed by CAT) or erode the vertebral body, so compromising the spinal support. Spontaneous closure of the AVF was observed in 1 case. Three cases were treated surgically with good results; two patients are waiting for embolisation. A review of the literature provides complementary information on the long-term evolution of these AVF and confirms the need for systematic therapy as demonstrated in our study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092766 TI - [Aneurysm of the sinus of Valsalva in children and young adults. Apropos of 9 cases]. AB - Nine cases (7 boys and 2 girls) of aneurysm of the sinus of Valsalva (SVA) diagnosed before 19 years of age are reported. Group 1 comprised 5 children aged 5 to 14 years without rupture of the aneurysm; 3 had an associated ventricular septal defect (VSD). The diseased sinus was the right anterior sinus in 4 cases and the posterior sinus in one case. The diagnosis was made by 2D echocardiography, performed in 3 patients for follow-up of a VSD and in 2 patients to investigate a systolic murmur. Group 2 comprised 4 patients under 19 years of age with SVA which ruptured into in the right heart cavities. One of these patients had a known right anterior SVA diagnosed at angiography performed to investigate a VSD when the child was 4 years old. The rupture occurred suddenly when the child was 14. These cases of SVA involved the right anterior sinus with rupture into the right ventricle (3 cases) and the posterior non coronary sinus with rupture into the right atrium (1 case). A rupture syndrome was observed in 3 of the 4 patients with pulmonary oedema in 2 cases. The authors emphasise the rarity of SVA diagnosed before rupture and the low frequency of rupture before adulthood. Echocardiography is certainly the best method for diagnosing the condition and for following up these patients. PMID- 3092767 TI - [Hemodynamic effects of an alpha-blocking vasodilator in cardiac insufficiency caused by left-right shunt in children]. AB - The acute haemodynamic effects of an alpha-blocking vasodilator, nicergoline, observed during cardiac catheterisation were studied in 9 babies and 1 infant (mean age 11 months) with severe cardiac failure due to a large left-to-right interventricular shunt. Nicergoline was administered intravenously at a dose of 0.05 mg/kg/mn to 0.2 mg/kg/mn to lower mean systemic blood pressure by at least 10 mmHg. No significant changes in heart rate or in right and left atrial pressures were observed. On the other hand, mean systemic and pulmonary arterial pressures fell by 16% (p less than 0.001) and 13% (p less than 0.01) respectively. The ratio of pulmonary and systemic flow (Qp/Qs) decreased in 8 patients by an average of 21% (p less than 0.002). This fall was accompanied by a parallel reduction in oxygen concentrations of pulmonary arterial blood (16%) compared with mixed venous blood. However, the Qp/Qs ratio increased in the other 2 patients by over 50%. In the group of 8 patients in which the left-to-right shunt decreased, the ratio of pulmonary to systemic resistance (Rp/Rs) increased by 33% (p less than 0.002) whilst this value fell by 36% in the 2 patients in whom the volume of the shunt increased. There were no discriminatory parameters between the two groups with regards to age, pulmonary artery pressures, the volume of the shunt (Qp/Qs) or level of pulmonary resistances (Rp/Rs) to explain the variability of the therapeutic response on the left-to-right shunt.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092768 TI - [Inferior vena caval return to the left atrium with intact interauricular septum. Apropos of 2 cases surgically treated with success]. AB - Two cases of abnormal inferior vena caval return to the left atrium are reported in a 9 year old boy and 13 year old girl. The diagnosis was suspected on the finding of severe cyanosis alone, and the anomalous systemic venous return was correctly identified by angiography of the inferior vena cava. There were three angiographic points of interest in these two cases: the normal position of the inferior vena cava, the absence of a left-to-right interatrial shunt and the presence of a vertical intra-left atrial "membrane" inserted behind the orifice of the inferior vena cava. Surgical correction consisted in resecting the inferior part of the interatrial septum and reconstructing a new septum behind the orifice of the inferior vena cava with a dacron patch in one case and by direct suture in the other. The good surgical result was controlled by angiography in both cases. In the second case, an intrapulmonary shunt due to multiple arteriovenous fistulae demonstrated by contrast echocardiography was responsible for persistent mild cyanosis for a few months after surgery. The long term clinical results were excellent in both cases. The authors review the literature of this rare malformation due to persistence of part of the right valve of the sinus venosus. PMID- 3092769 TI - [Results of anatomical correction of simple transposition of the great vessels in 46 newborn infants]. AB - Between the 4th April 1984 and 6th December 1984, a strategy of anatomical correction of transposition of the great arteries was undertaken in the newborn if three criteria were respected: parental consent, patient's age of less than 15 days and satisfactory left ventricular geometry. We report our results in 47 consecutive cases operated by the same surgeon at an average age of 8.2 +/- 5.3 days. Atrioseptostomy was performed in all cases before surgery, with a ratio of left to right systolic ventricular pressures greater than 0.66 (m = 0.8) and an infusion of prostaglandin E1 was maintained until surgery in 40 cases. The geometry of the left ventricle assessed by echocardiography was considered to be normal in 23 cases, satisfactory in 22 cases and unfavourable in 2 cases. Except for one case with the great vessels situated in the frontal plane in which an atrial correction was decided upon during surgery, all the patients underwent detransposition under cardiopulmonary bypass without cardiac arrest, irrespective of the coronary anatomy. The pulmonary tract was reconstructed by direct anastomosis with a piece of tanned (first 25 cases) or autologous (following 21 cases) pericardium. There were 18 immediate deaths (17%) but only 4 out of 37 after September 1984 (11%); the causes of failure were: 5 technical errors, 1 irreducible postoperative pulmonary hypertension and 2 probable left ventricular failures. The 38 survivors were followed up for an average of 6.8 +/- 5.4 months (range 1 to 21 months; 28 cases were followed up for over 3 months).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092770 TI - [Evaluation of the systolic pressure of the right ventricle by echocardiographic study of left ventricular geometry]. AB - Right ventricular systolic pressure is an important parameter in paediatric cardiology. A critical haemodynamic situation is attained if it exceeds the systemic pressure: strain proximal to severe pulmonary stenosis or the result of pulmonary hypertension. In these circumstances, the patient must be closely followed up at the least, and appropriate treatment, often surgical, has to be instituted. Ambulatory methods of assessing this parameter are either unreliable, like the surface electrocardiogram, or relatively complex, like certain ultrasonic methods. We therefore looked for a method relating the systolic pressures of the two ventricles and the end systolic geometry of the left ventricle as assessed simply from a short axis view of the left ventricle at the level of the junction between the chordae and papillary muscles. Two orthogonal diameters are measured and the ratio of the two dimensions calculated: this ratio which we call the "septal curvature" reflects left ventricular compression by the pressure that the right ventricle exerts through the interventricular septum. Seventy-two children aged 6 hours to 18 years (average 5.2 years) hospitalised for pre or post-operative investigation of congenital heart disease were evaluated by this method. The results were compared by statistical analysis with the ratio of ventricular pressures measured directly almost simultaneously during cardiac catheterisation. In general, a linear relation was observed between septal curvature (x) and ratio of pressures (y); y = 0.88, x - 0.63 and R = 0.92.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092771 TI - [Surgical treatment of complete atrioventricular canals, regular and irregular forms, in 75 patients]. AB - The cases of 75 consecutive patients operated for complete atrioventricular canal between 1/1/1978 and 1/1/1985 at Marie-Lannelongue Hospital were reviewed. The age ranged from 1.5 months to 16 years. Forty-nine per cent of patients were operated in the first year of life in the period 1982-1984. Seventy-eight per cent of patients were operated before one year of age. Certain anatomical characteristics enable regular and irregular forms of the condition to be distinguished. Regular forms are characterised by the association of a defect of the inter atrio-ventricular septum, of a common atrioventricular orifice and of ventricles of equal volume without other associated malformations. Irregular forms include the parachute mitral valve, the double mitral orifice, deficient mitral valvular tissue, ventricular hypoplasia, subaortic stenosis, abnormal right ventricular muscular bands, associated cardiac malformations and pulmonary obstructive vascular disease. Surgery comprises repair of the ventricular septal defect and the ostium primum with two separate patches, respecting the anterior and posterior valves and partial or complete closure of the cleft valve. The hospital mortality rate was 33 p. cent. It was 16 p. cent in regular forms and 58 p. cent in irregular forms (p less than 0.01). The hospital mortality of patients operated before 1 year of age with the regular form of the malformation was 22 p. cent. Six children were reoperated secondarily with 2 deaths. Four pacemakers were implanted for complete atrioventricular block. The secondary mortality was 10 p. cent. Thirty-nine patients were followed up for an average of 28 months (range 3 months to 5.5 years).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092772 TI - [Measurement by Doppler echocardiography of the pulmonary arterial pressure in children with ductus arteriosus. Simultaneous Doppler and hemodynamic study]. AB - The aim of this study was to evaluate Doppler echocardiography in the non invasive assessment of pulmonary artery pressures in children with patent ductus arteriosus. Systolic pulmonary artery pressure was measured simultaneously at cardiac catheterisation and by pulsed Doppler in 11 children (mean age 1.8 +/- 2 years) with patent ductus arteriosus alone (6 cases) or associated with a malformation of the heart or great arteries (5 cases). Doppler assessment of systolic pulmonary artery pressure was performed by subtracting the value of the maximal pressure gradient between the aorta and pulmonary artery from the systolic systemic pressure measured simultaneously by sphygmomanometry. The maximal pressure gradient between the aorta and pulmonary artery was calculated using the modified Bernouilli formula and the maximal velocity (v) of the shunt flow (gradient = 4 v2). Ductal flow was recorded from the suprasternal approach by direct interrogation of the patent ductus visualised by 2D echocardiography. The systolic pulmonary arterial pressure measured by catheterisation ranged from 21 to 82 mmHg (mean 58 +/- 21 mm Hg) and by pulsed Doppler from 20 to 89 mm Hg (mean 56 +/- 24 mm Hg) (correlation r = 0.94). This study illustrates the value of Doppler echocardiography in the assessment of systolic pulmonary artery pressures in children with patent ductus arteriosus. PMID- 3092773 TI - [Value of the subxiphoid approach in 2-dimensional echocardiography for the diagnosis of ductus arteriosus in premature infants and infants]. AB - The preliminary results of our experience with the "inverted" subxiphoid approach for 2D echocardiographic visualisation of patent ductus arteriosus (PDA) in premature neonates and infants are reported. Eight premature ventilated neonates weighting 870 to 1,200 g with an isolated PDA were examined by this technique using a mechanical sector scanner and a 7.5 MHz transducer; three views were obtained (left ventricular outflow tract or "long axis"; an oblique view through the two atria and aortic arch; short axis view of the ventricles). A PDA was directly visualised in 6 of the 8 patients. It was possible to measure its diameter and observe its tortuous or rectilinear trajectory; the outcome of Indomethacin therapy or surgical ligature could also be evaluated. In the 2 patients in whom the PDA was not visualised, there were no clinical symptoms or echocardiographic signs of shunt: these PDA were therefore probably extremely small. In the neonate and infant, it is relatively easy to demonstrate a PDA by this approach. The PDA can also be followed up in "ductus dependent" congenital heart disease during treatment with Prostaglandin E. In conclusion, the subxiphoid approach represents an interesting alternative for the visualisation of PDA, especially in premature neonates in whom the suprasternal and parasternal views are often difficult to obtain. PMID- 3092774 TI - [Eisenmenger's syndrome and pregnancy]. AB - The consequences of pregnancy, abortion or tubal ligature were studied in 11 women with the Eisenmenger syndrome. Seventeen cases of pregnancy and 7 tubal ligatures were reviewed. In the 4 pregnancies continued of term and preceded by cardiac catheterisation, there were two maternal deaths on the 2nd and 7th day of the postpartum period due to pulmonary embolism confirmed in one case and suspected in the other. A third pregnancy was complicated by cerebral embolism and one case of tubal ligature was complicated by non-fatal pulmonary embolism. These cases were compared with previous reports in the literature to form a total of 42 cases of pregnancy in women with the Eisenmenger syndrome. The pregnancies were characterised by aggravation of dyspnoea and cyanosis in 72.4 p. cent of cases, by documented pulmonary embolism in 7 cases and by toxaemia of pregnancy in 26 p. cent of cases. The global mortality was 36 p. cent and all deaths but one occurred between the time of labour and the 11th postpartum day. Micro pulmonary thromboses were the commonest cause of death. Two mechanisms seem to combine to aggravate the cardiac status at the end of pregnancy and during the initial postpartum period: increased right-to-left shunt due to a rise in pulmonary resistances, due particularly to changes in coagulability favored by pregnancy; increased right-to-left shunt due to a decrease in systemic vascular resistances. A number of poor prognostic factors were identified: decreased oxygen saturation in arterial blood and toxaemia of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3092775 TI - [Fatal form of pericardo-myocarditis in Wissler-Fanconi syndrome]. AB - The Wissler-Fanconi syndrome is an inflammatory disease of unknown origin, similar to Still's disease, a systemic form of juvenile arthritis. The long-term evolution is marked by recurrent febrile exacerbations, sometimes complicated by pericardo-myocarditis which usually resolves without sequellae. The authors report a case with chronic pericardo-myocarditis progressing over a 7 year period to refractory congestive cardiac failure. PMID- 3092776 TI - [Congenital quadricuspid aortic valve. Apropos of a case. Review of the literature]. AB - The authors report a new case of quadricuspid aortic valve, a fortuitous finding in a 6 year old child. This rare congenital anomaly is usually isolated. The diagnosis is made by 2D echocardiography and the main risk is progression to severe aortic regurgitation in adulthood. PMID- 3092777 TI - Cellodextrin utilization and beta-glucosidase production by Bacteroides polypragmatus. AB - Bacteroides polypragmatus, a mesophilic obligate anaerobe, was shown to simultaneously ferment glucose and cellobiose giving ethanol as a major metabolic end-product. A mixture of higher cellodextrins was also utilized. The bacterium produced a beta-glucosidase with a pI value of 4.2 and a molecular weight of approximately 100,000 daltons. The enzyme was intracellular and functioned optimally at pH 7. The Km values obtained with p-nitrophenyl-beta-D-glucoside and cellobiose as substrates were 0.73 mM and 100 mM, respectively. The enzyme was quite stable at elevated temperatures; in the presence of 10% glycerol (v/v), it had a half-life of 4 h at 55 degrees C. It was also stable during long-term storage at either 4 degrees C or -20 degrees C, provided that 10% (v/v) glycerol was added to preparations maintained at -20 degrees C. PMID- 3092778 TI - Turnover of abnormal proteins in Bacillus megaterium and Saccharomyces cerevisiae: differences between in vivo and in vitro degradation. AB - Degradation of abnormal proteins in Bacillus megaterium and Saccharomyces cerevisiae in vivo was compared with that in cell-free extracts. Protein degradation in vivo, when the cells were labelled with 14C-leucine during growth in the presence of ethionine, was affected by the concentration of the analogue used. Proteins synthesized in the presence of 0.2-1 mM ethionine were degraded most rapidly in both organisms. The proteolytic enzyme system of yeast degraded the analogue-containing proteins in vitro faster than the normal proteins. This holds also for proteins synthesized in the presence of 5 mM ethionine, whose degradation in vivo was impaired. The proteolytic system of B. megaterium, on the other hand, was unable in vitro to differentiate between normal and abnormal proteins. Denatured proteins underwent preferential degradation over normal and ethionine-containing proteins. PMID- 3092779 TI - [Regressive hypertrophic myocardiopathy in an infant with Recklinghausen's neurofibromatosis]. AB - A case of neonatal hypertrophic cardiomyopathy (HCM) without obstruction is reported. Von Recklinghausen neurofibromatosis in the mother and several relatives and the occurrence of cafe-au-lait spots in the child at 6 weeks of life led to the association of HCM with this phacomatosis. The spontaneous regression of the myocardial hypertrophy after 6 weeks makes this first report of neonatal HCM in the course of Von Recklinghausen neurofibromatosis peculiar. Several reports in the literature mention the possibility of such a spontaneous regression of HCM or diffuse cardiac tumors, especially in the course of phacomatosis. PMID- 3092781 TI - Laboratory monitoring of nutritional support. Is more better? PMID- 3092780 TI - Carbon dioxide sensitivity in panic anxiety. Ventilatory and anxiogenic response to carbon dioxide in healthy subjects and patients with panic anxiety before and after alprazolam treatment. AB - One hypothesis that could account for the anxiogenic response to breathing air supplemented with carbon dioxide seen in panic anxiety patients is that panic patients might have abnormally high central medullary chemoreceptor sensitivity. Chemoreceptor sensitivity was assessed by using a rebreathing technique to measure the ventilatory response to CO2 in 14 medication-free patients with agoraphobia and panic attacks and 23 healthy subjects. Ventilatory response to CO2 was similar in patients and controls (mean +/- SEM, 1.58 +/- 0.16 vs 1.58 +/- 0.14 L/min/mm Hg), suggesting that abnormal chemoreceptor sensitivity does not explain the behavioral sensitivity of panic patients to CO2. Anxiety ratings increased markedly during rebreathing both in patients and controls; anxiety increases were significantly greater in patients than in healthy subjects matched for age, sex, and rebreathing duration. Alprazolam treatment in eight patients markedly attenuated anxiety increases during rebreathing. Differences in anxiogenic sensitivity to CO2 between patients and controls may be due to differences in the regulation of noradrenergic or other neuronal systems. PMID- 3092782 TI - When is a diagnostic test result positive? Decision tree models based on net utility and threshold. AB - The question "When is a diagnostic test result positive?" can be addressed by clinical decision analysis. We developed two simple decision tree models for selecting appropriate cutoff levels: a net utility model and a threshold model. These models have been incorporated in a software program for desktop computers. We believe it is important for investigators to provide raw data on test performance, for three reasons. First, these data can be used in simple decision tree models to identify "appropriate" cutoff levels. Second, they can be used to evaluate empiric cutoff levels or decision rules. Third, they can be used to evaluate optimal cutoff levels for detailed decision trees depicting specific clinical problems. PMID- 3092785 TI - [Nervous system of the kidney]. PMID- 3092783 TI - Induction of immunotoxicity in mice by polyhalogenated biphenyls. AB - Acute administration of Aroclor-1254 (500 mg/kg) or 3,4,5,3',4',5' hexabromobiphenyl (HBB) (2-6 mg/kg) IP, profoundly inhibited the plaque forming response to subsequent challenge with sheep erythrocytes in Ah locus positive (C57Bl/6N or B6C3F1N) mice. These studies showed: the immunotoxicity results paralleled enzyme induction results insofar as HBB was approximately 100 times more potent than Aroclor 1254; neither Aroclor nor HBB treatment caused significant induction in the Ah locus negative DBA/2N mice; when B6C3F1 mice were challenged with sheep red blood cells (SRBC) 6 or 16 weeks post Aroclor 1254 treatment, substantial recovery of a PFC response was observed; when these compounds were administered to older (76-week-old) (B6C3F1 mice, severe depression of a PFC response was observed. In contrast to its profound depression of a PFC response, Aroclor-1254 (up to 1250 mg/kg) caused slight increases in lymphocyte proliferation induced by either T or B cell mitogens. A single 500 mg/kg dose of Aroclor-1254 also suppressed the ability of recipient B6C3F1 animals to reject a challenge with either the syngenic fibrosarcoma (PYB6) or the gram negative pathogen (Listeria monocytogenes). PMID- 3092784 TI - Detection of HTLV-III/LAV antigens in peripheral blood lymphocytes from patients with AIDS. AB - HTLV-III was searched for in frozen sections of peripheral blood lymphocytes obtained from AIDS patients by an immunofluorescence technique. Human IgG against HTLV-III/LAV and monoclonal antibodies against HTLV-III/LAV P 24 antigen, yielded a strong cytoplasmic fluorescence in frozen sections of the lymphocytes. Some cells containing HTLV-III antigens displayed multinucleated giant forms. They also reacted with monoclonal antibodies against helper/inducer T-cells (OKT4+), as demonstrated by direct double staining immunofluorescence. Similarly, complexes of immunoglobulins and C3 component of complement were also detected on HTLV-III/LAV Ag expressing lymphocytes. Immunofluorescence study of frozen sections of peripheral blood lymphocytes appeared to be a simple, fast and reliable method for detection of HTLV-III/LAV Ag in AIDS patients. PMID- 3092787 TI - Visual acuity after treatment of persistent hyperplastic primary vitreous. PMID- 3092786 TI - [Pathomorphosis of bladder cancer after endolymphatic polychemotherapy]. AB - Clinical and morphological features of urinary bladder transitional carcinoma pathomorphosis after regional endolymphic polychemotherapy were studied to estimate the criteria of treatment efficiency and prognosis. Quantitative assessment of chemosensitive and chemoresistant tumours is given. The degree of cataplasia, growth character, the amount of stroma, blood supply and intensity of mononuclear infiltration predetermine the stage of pathomorphosis, efficiency of bladder cancer treatment. Studies of stromal immunomorphology, features of blood supply, mechanisms of neoplastic angiogenesis provide better understanding of biological nature of tumours, improve prognosis and choice of treatment. PMID- 3092788 TI - Chondroitin sulfate for corneal preservation at 4 degrees C. Evaluation by electron microscopy. AB - We tested three new corneal preservation media in which the dextran in McCarey Kaufman (M-K) medium was replaced by three preparations of chondroitin sulfate (CS): 1.5% CS, 5.0% CS, and 2.0% modified CS (K-Sol). One cornea from each of 36 pairs of corneas was placed in M-K medium and the opposite cornea was placed in one of the CS media. Endothelial preservation was evaluated by electron microscopy after storage at 4 degrees C for 1, 3, 5, 7, 10, and 14 days. We judged cellular preservation in a masked manner from the electron micrographs according to a morphologic grading system. Preservation in 1.5% CS solution was similar to that in M-K medium. Both 5.0% CS and K-Sol gave better endothelial preservation than M-K medium. The best preservation appeared to be in K-Sol, in which only 3% of the endothelial cells were disrupted after 14 days of storage at 4 degrees C. PMID- 3092789 TI - Replication of fungi in K-Sol corneal preservation medium at 4 degrees C. AB - We examined the growth of six fungi during 18 days at 4 degrees C in a corneal preservation medium containing 2.5% chondroitin sulfate (K-Sol). The number of viable organisms decreased with time for all six fungi, the average decrease being 65%. The risk of transplanting fungal organisms with a donor cornea stored for up to 18 days at 4 degrees C in preservation media containing chondroitin sulfate is no greater than that with the same cornea stored for only one day. PMID- 3092790 TI - Massive retinal gliosis. A reactive proliferation of Muller cells. AB - Both Muller cells and astrocytes have been implicated in the dispute over the histogenesis of massive retinal gliosis. We studied three cases of massive retinal gliosis by light and electron microscopy and immunocytochemistry. Spindle fibrillary glial cells were joined by zonulae adherentes resembling those of the external limiting membrane of the retina. Furthermore, these cells produced a continuous basement membrane around an extracellular space filled with fine filaments, which was highly suggestive of vitreous cavity. In the proliferating cells, immunoperoxidase technique disclosed the presence of carbonic anhydrase isoenzyme C, characteristically found only in Muller cells. The glial cells in the preretinal membrane away from the gliotic nodule showed similar characteristics. We concluded that both the nodule of massive retinal gliosis and the associated preretinal glial membrane resulted from the proliferation and migration of Muller cells. PMID- 3092791 TI - The nutritional management of obese patients--a utilisation review. PMID- 3092792 TI - Ipsilateral motor seizures. AB - A patient presented with elementary partial motor seizures on the same side as the cerebral lesion. A cerebral computerised tomographic scan showed a right medial frontal atrophic lesion and an electroencephalogram showed seizure discharges from the same region. The clinical significance and pathophysiology of ipsilateral seizures are discussed. PMID- 3092794 TI - Distinction of two CD3-monoclonal antibodies in respect to the effectivity to modulate the induction of IgM- and gamma-interferon synthesis. AB - Monoclonal antibodies which specifically bind to epitopes within the T3-antigen complex (CD3 mAb) are excellent tools to analyse mechanisms of T-cell activation and of the interactions between T-cells, B-cells, accessory cells and intermediating immunefactors. In the present study we could show, that the CD-3 mAbs BMA 030 and BMA 031 are highly effective in modulating immunereactions, similar to antibodies directed to the T4-antigen (CD4-mAb) or the T8-antigen (CD8 mAbs) respectively. The data substantiate that depending on the experimental system BMA 030 and BMA 031 are clearly distinctive in their efficacy to modulate immunereactions. For therapeutical use of CD-3-monoclonal antibodies in organ transplantation those clone-specific differences of mAbs with identical binding specificity might cause for crucial differences in clinical applicability. PMID- 3092793 TI - Quality criteria for i.v.-immunoglobulins: importance of tests and product properties. AB - Quality criteria for i.v.-immunoglobulins (i.v.- Igs) are critically discussed laying emphasis on spontaneous anticomplementary activity (aca) and size dependent composition. Considering the percentage of fractions obtained by gel filtration (Ultrogel AcA 34), however, the monomeric IgG containing fraction contributed the major part of aca under the experimental conditions chosen. Subclass IgG3 seems to contribute considerably to aca. No correlation was found between aca and the percentage of fractions containing components larger in size than IgG dimers in various commercially available Igs. Moreover, the subclass distribution in different batches of individual products showed considerable variations. The amount of IgG4 is correlated with that of IgA in chemically unmodified products relatively poor in IgA (approx. less than or or equal to 10 mg/5 g Ig), indicating that attempts to reduce IgA consequently result in removal of IgG4. PMID- 3092795 TI - Effect of recombinant human interferon gamma and interleukin 2 on CFU-GM. AB - Human bone marrow CFU-GM were cultured with rHu-GM-CSF and varying concentrations of rHu-gamma-IFN. Concentration-dependent suppression of CFU-GM precursors by gamma-IFN was demonstrated. This suppression was, in part, reversible by addition of rHu-IL-2. Reversal was also concentration-dependent. Both immune-regulatory T cell mediators seem to act on a more primitive stage of committed progenitor cell development. PMID- 3092796 TI - The influence of (+/-)-15-deoxyspergualin on experimental transplantation and its immunopharmacological mode of action. AB - 15-Deoxyspergualin, a novel structure which was described to have anti-tumor activity, was tested on its influence on the survival time of transplanted organs. Prolongation of graft survival was demonstrated in rat skin (LEW--- Fischer), islet cells heart and kidney transplantation (DA----LEW) as well as in allogeneic tumor transplantation in mice (C57Bl/6----Balb/c). Especially in the kidney transplantation a long-lasting transplant survival time was observed, indicating induction of tolerance. Examination of its immunopharmacological properties showed that the mononuclear phagocytes and not the lymphocytes are primarily affected by the substance, thus expressing a new mode of action for a substance being effective in transplantation immunology. PMID- 3092797 TI - The stability of the specific-mate recognition system of Drosophila melanogaster. PMID- 3092798 TI - Chemosensory elements of courtship in normal and mutant, olfaction-deficient Drosophila melanogaster. PMID- 3092800 TI - Measuring learning in individual flies is not necessary to study the effects of single-gene mutations in Drosophila: a reply to Holliday and Hirsch. PMID- 3092799 TI - The influence of light on pupation height in Drosophila. PMID- 3092802 TI - [Thrombopheresis with the CS-3000 cell separator. Changes in primary hemostasis in the donor and in concentrates in 8-day storage]. PMID- 3092801 TI - Blood gas and acid-base balance during cardiopulmonary resuscitation by intrathoracic and abdominal pressure variations. AB - The blood gases and acid-base balance in a modified cardiopulmonary resuscitation (CPR) technique, based on intrathoracic and abdominal pressure variations by means of circumferential chest and abdominal balloon inflation, were examined in seven mongrel dogs. CPR proceeded for periods lasting 30 min or more and was monitored by measurements of aortic and right ventricular pressures and carotid blood flow during the compression (artificial systole) and the relaxation phase (artificial diastole). The carotid blood flow was 21.7 +/- 7.8 (mean +/- SD) ml/min, which was 0.18 +/- 0.6 (mean +/- SD) of the baseline mean carotid flow. Arterial blood was well oxygenated throughout the experiments, and low PCO2 levels (5-9 mm Hg) caused an initial severe alkalosis (pH = 7.94). However, a gradual decline in the pH was observed, reaching a value of 7.34 +/- 0.11 in the arterial blood after 30 min of CPR. The venous blood had a very low oxygen content (less than 25.5%) with a low PO2 and a normal PCO2 (43.7 +/- 7.3 mm Hg) throughout the experiment. A gradually developing metabolic acidosis was reflected in the pH values, and an increase in base deficit from 2.25 +/- 5.6 meq/1 prior to CPR to 16.7 +/- 3.2 meq/1 after 30 min of CPR was observed. High arteriovenous differences in oxygen content (greater than 66.4%) and CO2 tension (30.1-41.5 mm Hg) with a slowly developing metabolic acidosis were noted. Thus, CPR by thoracic and abdominal pressure variations is associated with a slowly developing metabolic acidosis which is the result of the combination of hyperventilation and a low perfusion state. PMID- 3092803 TI - Molybdenum hydroxylases in Drosophila. III. Further characterization of the low xanthine dehydrogenase gene. AB - The biochemical effects of several newly induced low xanthine dehydrogenase (lxd) mutations in Drosophila melanogaster were investigated. When homozygous, all lxd alleles simultaneously interrupt each of the molybdoenzyme activities to approximately the same levels: xanthine dehydrogenase, 25%; aldehyde oxidase, 12%; pyridoxal oxidase, 0%; and sulfite oxidase, 2% as compared to the wild type. In order to evaluate potentially small complementation or dosage effects, mutant stains were made coisogenic for 3R. These enzymes require a molybdenum cofactor, and lxd cofactor levels are also reduced to less than 10% of the wild type. These low levels of molybdoenzyme activities and cofactor activity are maintained throughout development from late larval to adult stages. The lxd alleles exhibit a dosage-dependent effect on molybdoenzyme activities, indicating that these mutants are leaky for wild-type function. In addition, cofactor activity is dependent upon the number of lxd+ genes present. The lxd mutation results in the production of more thermolabile XDH and AO enzyme activities, but this thermolability is not transferred with the cofactor to a reconstituted Neurospora molybdoenzyme. The lxd gene is localized to salivary region 68A4-9, 0.1 map unit distal to the superoxide dismutase (Sod) gene. PMID- 3092804 TI - Pigment patterns in mutants affecting the biosynthesis of pteridines and xanthommatin in Drosophila melanogaster. AB - Eye-color mutants of Drosophila melanogaster have been analyzed for their pigment content and related metabolites. Xanthommatin and dihydroxanthommatin (pigments causing brown eye color) were measured after selective extraction in acidified butanol. Pteridines (pigments causing red eye color) were quantitated after separation of 28 spots by thin-layer chromatography, most of which are pteridines and a few of which are fluorescent metabolites from the xanthommatin pathway. Pigment patterns have been studied in 45 loci. The pteridine pathway ramifies into two double branches giving rise to isoxanthopterin, "drosopterins," and biopterin as final products. The regulatory relationship among the branches and the metabolic blockage of the mutants are discussed. The Hn locus is proposed to regulate pteridine synthesis in a step between pyruvoyltetrahydropterin and dihydropterin. The results also indicate that the synthesis and accumulation of xanthommatin in the eyes might be related to the synthesis of pteridines. PMID- 3092805 TI - Two distinct forms of glutathione transferase from human foetal liver. Purification and comparison with isoenzymes isolated from adult liver and placenta. AB - Isoelectric focusing of a cytosol fraction from human foetal liver revealed the existence of an acidic and a basic isoenzyme of GSH transferase. The acidic and basic forms of GSH transferase were purified in good yield by use of ion-exchange chromatography on DEAE-cellulose followed by affinity chromatography on S-hexyl GSH coupled to epoxy-activated Sepharose 6B. The content of the acidic and the basic isoenzymes of GSH transferase together was calculated to constitute 1-2% of the soluble proteins in the hepatic cytoplasm. Physical, catalytic and immunological analyses of the acidic and the basic isoenzymes from foetal liver demonstrated unambiguously that the two forms are different structures with distinct properties. On the other hand, the results show clearly extensive similarities between the foetal acidic transferase and transferase pi from human placenta as well as between the foetal basic form and the basic isoenzymes isolated from adult liver. An exception is that both foetal enzymes seem to be considerably more efficient in catalysing the conjugation of GSH with styrene 7,8 epoxide than the corresponding adult forms of GSH transferase. PMID- 3092806 TI - Ribulose 1,5-bisphosphate carboxylase. Effect on the catalytic properties of changing methionine-330 to leucine in the Rhodospirillum rubrum enzyme. AB - Oligonucleotide-directed mutagenesis of cloned Rhodospirillum rubrum ribulose bisphosphate carboxylase/oxygenase with a synthetic 13mer oligonucleotide primer was used to effect a change at Met-330 to Leu-330. The resultant enzyme was kinetically examined in some detail and the following changes were found. The Km(CO2) increased from 0.16 to 2.35 mM, the Km(ribulose bisphosphate) increased from 0.05 to 1.40 mM for the carboxylase reaction and by a similar amount for the oxygenase reaction. The Ki(O2) increased from 0.17 to 6.00 mM, but the ratio of carboxylase activity to oxygenase activity was scarcely affected by the change in amino acid. The binding of the transition state analogue 2-carboxyribitol 1,5 bisphosphate was reversible in the mutant and essentially irreversible in the wild type enzyme. Inhibition by fructose bisphosphate, competitive with ribulose bisphosphate, was slightly increased in the mutant enzyme. These data suggest that the change of the residue from methionine to leucine decreases the stability of the enediol reaction intermediate. PMID- 3092808 TI - Isolation of streptococcal hyaluronate synthase. AB - Hyaluronate synthase was isolated from protoblast membranes of streptococci by Triton X-114 extraction and cetylpyridinium chloride precipitation. It was identified as a 52,000-Mr protein, which bound to nascent hyaluronate and was affinity-labelled by periodate-oxidized UDP-glucuronic acid and UDP-N acetylglucosamine. Antibodies directed against the 52,000-Mr protein inhibited hyaluronate synthesis. Mutants defective in hyaluronate synthase activity lacked the 52,000-Mr protein in membrane extracts. Synthase activity was solubilized from membranes by cholate in active form and purified by ion-exchange chromatography. PMID- 3092807 TI - Liberation of [3H]arachidonic acid and changes in cytosolic free calcium in fura 2-loaded human platelets stimulated by ionomycin and collagen. AB - Cytosolic Ca2+ levels and arachidonate liberation were investigated in platelets loaded with the fluorescent Ca2+ indicator dye fura-2, and labelled with [3H]arachidonate. Fura-2 was used in preference to quin2 because the latter interfered with [3H]arachidonate labelling of phospholipids. From a resting free Ca2+ level of around 100 nM, ionomycin (10-200 nM) evoked an instantaneous, concentration-dependent increase in cytosolic Ca2+ that only resulted in [3H]arachidonate liberation (up to 4-fold over control) at Ca2+ levels greater than 1 microM. Addition of collagen (10 micrograms/ml) evoked an elevation in Ca2+ up to 461 +/- 133 nM. These changes in Ca2+ were accompanied by a 2-4-fold elevation in [3H]arachidonate with depletion of [3H]phosphatidylcholine by 17 +/- 4% and [3H]phosphatidylinositol by 41 +/- 7%. Indomethacin (10 microM) reduced the elevation in Ca2+ by collagen to 115 +/- 18 nM but did not significantly inhibit the 2-4-fold increase in [3H]arachidonate. [3H]Phosphatidylcholine and [3H]phosphatidylinositol were decreased by 9 +/- 7% and 10 +/- 6%, respectively, with collagen in the presence of indomethacin. Stimulation of phosphoinositide turnover by collagen in the presence and absence of indomethacin was indicated by [32P]phosphatidate formation in cells prelabelled with [32P]Pi. This phosphatidate formation was decreased (75%) by the presence of indomethacin. In the presence of indomethacin, phorbol myristate acetate (20 nM) alone or in combination with ionomycin (30 nM) failed to stimulate arachidonate liberation despite a marked stimulation of aggregation. These results indicate that, whereas ionomycin requires Ca2+ in the microM range for arachidonate liberation, collagen, notably in the presence of indomethacin, does so at basal Ca2+ levels. The mechanisms underlying the regulation of arachidonate release by collagen are not clear, but do not appear to involve activation of protein kinase C, or an elevation of cytosolic free Ca2+. PMID- 3092809 TI - Polyamine-mediated turnover of ornithine decarboxylase in Chinese-hamster ovary cells. AB - We have used Chinese-hamster ovary (CHO) cells maintained in a chemically defined medium to study the regulation of ornithine decarboxylase (ODC) by polyamines. Cells maintained in the defined medium had no detectable putrescine, and approx. 1-3 units of ODC activity/10(6) cells, where 1 unit corresponds to 1 nmol of substrate decarboxylated in 30 min. The defined medium is ornithine-deficient, thus limiting the exogenous substrate for ODC, and subsequently decreasing intracellular polyamine accumulation. Restoration of intracellular putrescine and increased formation of spermidine by addition of exogenous ornithine or putrescine led to a marked decrease in ODC activity, which was paralleled by a decrease in a alpha-DL-difluoromethyl[3,4-3H]ornithine (DFMO)-binding protein of Mr approx. 53,000, which is precipitable with anti-ODC antibody. Calculation of DFMO binding per unit of activity showed no change in the specific activity of the enzyme. We identified [35S]methionine-labelled peptides corresponding to ODC by immunoprecipitation of radiolabeled whole cell proteins. Only one protein was precipitated, of Mr approx. 53 000, which co-migrated with the DFMO-binding protein. Immunoprecipitation of radiolabelled proteins from cells incubated in the presence of exogenous ornithine indicated that the observed activity decrease was not due to an inhibition of ODC protein synthesis. Analysis of immunoprecipitable ODC protein from cells that had been pulse-labelled with [35S]methionine, and then treated for 5 h with 100 microM-ornithine, -putrescine or -spermidine, revealed a distinct disappearance of labelled ODC protein after restoration of intracellular polyamine pools. No detectable turnover of ODC was observed in the absence of exogenous polyamine treatment. These data support the hypothesis that ODC protein, and subsequent activity, is regulated by intracellular polyamine content through mechanisms that influence turnover of the enzyme. PMID- 3092810 TI - Identification of lysine at the active site of human 5-aminolaevulinate dehydratase. AB - Reduction of human 5-aminolaevulinate dehydratase with NaBH4 in the presence of 14C-labelled substrate led to complete loss of catalytic activity and to incorporation of label into the enzyme protein. By comparison with authentic lysyl-aminolaevulinic acid, prepared chemically, the modified active-site amino acid obtained by acid hydrolysis was shown to be lysine. Sequencing of a CNBr cleavage peptide isolated from the inactivated 14C-labelled enzyme revealed that the lysine was present within the sequence M-V-K-P-G-M. PMID- 3092811 TI - Evidence for rapid metabolic turnover of hyaluronate synthetase in Swarm rat chondrosarcoma chondrocytes. AB - Synthesis of [3H]hyaluronate from [6-3H]glucosamine was investigated in cultures of Swarm rat chondrosarcoma chondrocytes treated with various concentrations (0.1 microM-0.1 mM) of cycloheximide for various times. Concentrations greater than 1 microM inhibited protein synthesis by greater than 90%. Hyaluronate synthesis was decreased, with a t1/2 for 50% inhibition of 80-120 min, depending on the concentration of cycloheximide present. Similar experiments using [1-3H]glucose as a precursor label gave similar results. Experiments using [6-3H]glucosamine as a precursor label and 0.18 mM-puromycin to inhibit protein synthesis inhibited hyaluronate synthesis (t1/2 = 82 min) with similar kinetics to cycloheximide induced inhibition. Cultures incubated with 3.6 microM-cycloheximide for up to 9 h and supplemented with p-nitrophenyl beta-D-xyloside during the last 75 min of treatment showed increased synthesis of [3H,35S]chondroitin sulphate, demonstrating that UDP-hexose precursors for glycosaminoglycan synthesis are not rapidly depleted on blockage of protein synthesis. Rapid metabolic turnover of hyaluronate synthetase is the most likely cause for decreased hyaluronate synthesis in chondrocytes in which protein synthesis is inhibited. PMID- 3092812 TI - A thiol-sensitive degradative process of liver uncouples autophosphorylation of the insulin receptor from insulin binding. AB - Insulin receptors derived from highly purified rat liver plasma membranes and Golgi membranes showed differences in insulin-mediated receptor autophosphorylation, even though their insulin-binding characteristics were similar. This difference was related to the generation of a Mr-84,000 fragment of the Mr-90,000 beta subunit of the plasma-membrane receptor, a fragment that was not present in the receptor from Golgi membranes, in the absence of a change in the insulin-binding alpha subunit. When autophosphorylation activity was based on insulin binding, the activity of the plasma-membrane-derived insulin receptor was decreased to 25-30% that of the Golgi-derived receptor. Endoglycosidase F digestion produced changes in the Mr values for both species, but they were not converted into a single subunit, thereby suggesting differences in the protein component of the two subunits. Although the proteinase inhibitors phenylmethanesulphonyl fluoride, ovomucoid and aprotinin failed to block the formation of the Mr-84,000 fragment, the presence of iodoacetamide or EDTA during liver homogenization markedly inhibited fragment generation and allowed the plasma-membrane insulin receptor to retain an autophosphorylation activity comparable with that present in insulin receptors from Golgi membranes. Thus a thiol-sensitive, cation-dependent, degrading activity has been identified that can uncouple the insulin-binding activity of the plasma-membrane insulin receptor from its tyrosine kinase activity. PMID- 3092814 TI - Single step isolation of immunofluorescence-stained, viable lymphocytes by fluorescence-activated cell sorter using ethidium bromide. AB - The paper presents a method for preparation of viable, immunofluorescence-stained lymphocytes in a single isolation step by fluorescence-activated cell sorter. Discrimination between viable, immunofluorescence positive cells and nonspecifically stained dead cells was carried out on the basis of the DNA specific dye ethidium bromide. Ethidium bromide enters cells with damaged plasma membrane only. The method is described by the example of isolation of Lyt-2 positive mouse lymph node cells. PMID- 3092815 TI - Effects of bacterial sepsis on protein metabolism in infants during the first week. AB - In the presence of bacterial infection during the first week of life a catabolic state evolves more rapidly than in the later life. Hyperaminoacidaemia and subsequent hyperaminoaciduria, elevated urea concentrations in serum, and increased renal nitrogen losses are the most important metabolic changes. These findings correlate with the clinical course of the disease and refer to the primary disturbance of cell metabolism as the cause of the metabolic changes observed. While no relation could be observed between metabolic response and bacterial species, there is a significant dependence on the time interval from the occurrence of first clinical symptoms at the beginning of antibiotic treatment. If this period is longer than 8 h, serious metabolic disturbances will usually be found. Due to the limited amino acids utilization, especially by the liver, an adequate energy intake should be the primary aim of nutrition, whereas a protein intake of more than 2.0 to 2.5 g/kg X day may further aggravate the metabolic imbalance. PMID- 3092813 TI - Chemical characterization of cell-CAM 105, a cell-adhesion molecule isolated from rat liver membranes. AB - Cell-CAM 105, a glycoprotein that is involved in recognition and adhesion between isolated rat hepatocytes in vitro, was purified to homogeneity by a combination of immunoaffinity chromatography, gel-exclusion chromatography and ion-exchange chromatography. Electrophoretic, compositional and enzymic analyses were performed and the glycoprotein was shown to consist of two peptide chains, of apparent Mr 110,000 and 105,000 respectively, that are glycosylated to similar extents. Carbohydrate analyses demonstrated the presence of sialic acid, galactose, mannose, fucose and glucosamine, but no galactosamine, indicating that only N-linked oligosaccharides occurred. The total content of carbohydrate amounted to 33%. Peptide mapping indicated that the two peptide chains were structurally very similar. After incubation of cultured hepatocytes with [32P]Pi, phosphorylated cell-CAM 105 could be isolated. Both peptide chains were labelled and phospho-amino-acid analysis demonstrated that serine residues had become phosphorylated. A significant feature of cell-CAM 105 was a susceptibility to autolytic degradation that was difficult to inhibit. The major degradation products had apparent Mr 90,000 and 70,000, respectively. The effect of purified cell-CAM 105 on cell-cell adhesion of re-aggregating hepatocytes was studied. A significant inhibition was observed, indicating that the protein is directly involved in intercellular adhesion of these cells. PMID- 3092816 TI - Induction of mammalian stress proteins by a triethylphosphine gold compound used in the therapy of rheumatoid arthritis. AB - In vitro exposure of cultured human, murine and rat cells to pharmacologic concentrations (10(-8) to 10(-6) M) of auranofin, 2,3,4,6,-tetra-O-acetyl-1-thio beta-D-glucopyranosato-S- triethylphosphine gold(I) (Ridaura), a gold containing compound approved for the treatment of rheumatoid arthritis, results in the induction of several stress proteins. The enhanced synthesis of two polypeptides, p32 and p34, was particularly prominent. A similar response was observed in freshly collected human monocytes challenged with auranofin. In addition, oral administration of auranofin to rats induced enhanced synthesis of a 32-kDa protein in peritoneal exudate cells analyzed ex vivo at various times following drug treatment. These data suggest that increased synthesis of p32 and p34 might participate in mediating certain aspects of auranofin pharmacology. PMID- 3092817 TI - A homodimer of the beta-subunits of inhibin A stimulates the secretion of pituitary follicle stimulating hormone. AB - A 24,000 Dalton protein with follicle stimulating hormone (FSH)-releasing activity, named activin, has been characterized previously from porcine follicular fluid as a heterodimer composed of the beta-subunits of inhibins A and B linked by disulfide bond(s) [Ling et al. (1986) Nature, in press]. In this paper we report the isolation of another 24,000 Dalton protein with FSH-releasing activity from porcine follicular fluid, using successive steps of heparin Sepharose affinity chromatography, gel filtration on Sephacryl S-200, and four steps of reversed-phase HPLC, followed by preparative sodium dodecyl-sulfate polyacrylamide gel electrophoresis chromatography. Based on the molecular weight of the isolated molecule and its deduced NH2-terminal sequence, we propose that this second FSH-releasing substance present in porcine follicular fluid is a homodimeric protein composed of two beta-subunits of inhibin A joined together by disulfide bond(s). The name homo-activin-A is proposed for this substance. PMID- 3092818 TI - Albumin does not inhibit endothelium-dependent relaxation. AB - Bovine serum albumin which is fatty acid free, enhances the endothelium-dependent vasodilating effect of various agonists like acetylcholine, carbachol, ATP, ADP and ionophore on rat aortic rings. The maximum effect was observed in buffers containing 5% albumin. Albumin has no effect on rings devoid of endothelium. On the other hand, both plasma and serum completely abolished the vasodilating effect of these agents. PMID- 3092819 TI - Growth hormone-releasing hormone and clonidine stimulate biosynthesis of growth hormone in neonatal pituitaries. AB - Comparative studies were performed to verify the effect of growth hormone releasing hormone (GHRH) or clonidine (CLON), a compound thought to act via release of endogenous GHRH, in stimulating GH biosynthesis in the pituitary from neonatal and adult rats. In vitro preincubation for 1 h with GHRH (hpGRF-40, 10( 8) M) increased the incorporation of L-[3H]leucine in the electrophoretic band of GH in the pituitary from 10-day-old rats, but not in the gland from adult rats. Ex-vivo treatment with GHRH or CLON for 5 days was effective in stimulating GH biosynthesis only in the pituitary from neonatal rats. These data demonstrate that neonatal somatotropes are particularly sensitive to the GH-synthesizing activity of GHRH or a GHRH-releasing stimulus. PMID- 3092820 TI - An ubiquinone-binding protein in mitochondrial NADH-ubiquinone reductase (Complex I). AB - An ubiquinone-binding protein (QP) was purified from mitochondrial NADH ubiquinone reductase (Complex I). Complex I was separated into 3 fragments: a fraction of hydrophobic proteins, that of soluble iron-sulfur protein (IP) and soluble NADH dehydrogenase of flavoprotein by a procedure involving the resolution with DOC and cholate, followed by ethanol and ammonium acetate fractionations. About 40% of the total ubiquinone was recovered in the IP fragment which consisted of 12 polypeptides. The QP was purified from the IP fragment with a hydrophobic affinity chromatography. SDS-polyacrylamide gel electrophoresis showed that the purified QP corresponded to 14-kDa polypeptide of the IP fragment and was a different protein from the QP (12.4 kDa) in Complex III. The purified QP (14 kDa) contained one mol ubiquinone per mol. The ubiquinone-depleted IP fragment could rebind ubiquinone. These results indicate that an ubiquinone-binding site in Complex I is on the 14-kDa polypeptide of the IP fragment. PMID- 3092821 TI - Gamma interferon is able to enhance the oxidative metabolism of human neutrophils. AB - The oxidative metabolism of human neutrophils has been studied after incubation of the cells with recombinant interferon-y. Neutrophils incubated for 2-4 hours with 2-50 U/ml recombinant interferon-y undergo a higher respiratory burst measured both as Oz consumption and Oz- production when stimulated with formyl methionyl-leucyl-phenylalanine, Concanavalin A or phorbol myristate acetate. The potentiating effect of interferon-y requires more than one hour of incubation, is optimal at 20-50 U/ml and depends on the presence of serum in the incubation medium. The interferon effect depends on new protein synthesis. Cycloheximide at doses which do not alter the respiratory response of normal cells completely prevents the potentiating effect of interferon. PMID- 3092822 TI - Phorbol ester-induced alteration of protein kinase C catalytic properties occurs at the membrane level and is not reproduced by physiological stimuli. AB - Potent tumor promoter TPA (1-100 nM) has previously been shown to induce a striking alteration of protein kinase C catalytic properties in target cells (C. Cochet et al., 1986, Biochem. Biophys. Res. Comm. 134, 1031-1037). This alteration contributes to the apparent loss of cellular protein kinase C, secondary to TPA treatment, when the enzyme is probed by its phospholipid dependent histone kinase activity. This effect was observed as well when rat-1 cells were treated by other tumor promoters such as mezerein, teleocidin, aplysiatoxin and palytoxin, whereas inactive phorbol ester structures were ineffective. On the other hand, 1,2-dioctanoyl glycerol did not induce that effect. This protein kinase C alteration was shown to occur at the cellular membrane level. It is suggested that membrane translocation and activation of protein kinase C induced by potent tumor promoter structures are not functionally equivalent to that secondary to physiological stimuli. Although the mechanisms underlying this phenomenon remains to be understood at the molecular level, it may be of significance in the process of tumor promotion. PMID- 3092823 TI - Presence of interleukin 3-like activity in the supernatants of lipopolysaccharide stimulated mouse splenocytes. AB - An Interleukin 3 (IL 3) activity was found in the supernatants of mouse spleen cells stimulated by lipopolysaccharide (LPS). The IL 3 activity was maximum in the supernatants of 5 to 7 days cultures. IL 3 activity was assessed by the capacity of the spleen cell supernatants to allow the growth of the FDC-P2 cell line, a strictly IL 3 dependent cell line. Polymyxin B could inhibit the IL 3 induction by LPS. PMID- 3092824 TI - Rat heart cell membranes contain three substrates for cholera toxin-catalyzed ADP ribosylation and a single substrate for pertussis toxin-catalyzed ADP ribosylation. AB - Three peptides (Mr = 45,000, 47,000 and 52,000) in the cholate extract from rat heart cell membranes were radiolabeled when the extract was incubated in the presence of activated cholera toxin and [32P]NAD. A single peptide of Mr = 41,000 in this extract was ADP-ribosylated by pertussis toxin in the presence of [32P]NAD. PMID- 3092825 TI - Inhibition of muscle glycogen phosphorylase b by vitamin B2 and its coenzyme forms. AB - Kinetic studies have demonstrated that vitamin B2 and its coenzyme forms FMN and FAD are potent inhibitors of glycogen phosphorylase b from rabbit skeletal muscle. The inhibition of the enzyme by flavins has a co-operative character (Hill coefficients exceed unity). Glycogen phosphorylase b bound to FMN or FAD does not reveal catalytic activity, whereas the enzyme bound to riboflavin retains about 16% of the initial catalytic activity. PMID- 3092826 TI - Binding of vitamin B2 and its coenzyme forms by muscle glycogen phosphorylase b. AB - Binding of vitamin B2 and its coenzyme forms by glycogen phosphorylase b was studied by sedimentation velocity and sedimentation equilibrium methods. Microscopic dissociation constants for complexes of the enzyme with riboflavin, FMN and FAD were found to be 12.5, 6.8 and 18.1 microM, respectively (0.1 M KCl, pH 6.8, 20 degrees C). We revealed also that glucose 1-phosphate, glycogen and AMP decreased the affinity of the enzyme for FMN. PMID- 3092828 TI - Lanthanide ions and Cd2+ are able to substitute for Ca2+ in regulating phosphorylase kinase. AB - Trivalent lanthanide ions and Cd2+ were found to mimic effectively the stimulatory action of Ca2+ on rabbit muscle phosphorylase kinase. In the range of concentrations tested, Cd2+ and lanthanides (Tb3+, Gd3+, Pr3+, Ce3+) could substitute for Ca2+ in activating the enzyme to about 60% and 70% respectively of the maximal level seen with Ca2+, at pH 8.2. The effect induced by Cd2+ was biphasic (stimulation followed by inhibition with increasing metal cation concentration). Similar results were obtained at pH 6.8. Cd2+ and Tb3+ were also able to replace Ca2+ required for the stimulation of phosphorylase kinase activity at pH 8.2 by exogenous calmodulin. Maximal stimulation induced by calmodulin in presence of Cd2+ was significantly higher than that in presence of Ca2+ or Tb3+. PMID- 3092827 TI - Ornithine decarboxylase activity and actin polymerization in testosterone- stimulated mouse kidney. AB - Renal hypertrophy was induced in mice by injection of testosterone. Associated with an increase in renal tissue mass were increases in the concentrations of spermine and spermidine and in the activity of ornithine decarboxylase (ODC), the rate limiting enzyme in their synthesis. The increased activity of ODC was shown to be due to an increase in tissue ODC content. Total tissue actin was not altered by testosterone treatment although the proportion of unpolymerized (soluble) actin was increased significantly. These data are discussed in relation to the postulated mechanism of polyamine stimulation of actin polymerization. PMID- 3092829 TI - Inhibition by ebselen of microsomal NADPH-cytochrome P450-reductase in vitro but not in vivo. PMID- 3092831 TI - Developmental alterations in hepatic UDP-glucuronosyltransferase. A comparison of the kinetic properties of enzymes from adult sheep and fetal lambs. AB - The kinetic properties of hepatic microsomal UDP-glucuronosyltransferase were studied in sheep in the perinatal period, using acetaminophen as the aglycone. Kinetic analyses indicated that activity at Vmax was significantly less in fetal microsomes (113, 135 or 141 days) as compared with the adult sheep. However, these differences between fetal and adult animals were not due simply to smaller amounts of UDP-glucuronosyltransferases catalyzing conjugation of acetaminophen in fetuses versus adults. Thus, the kinetic properties of UDP glucuronosyltransferase(s) were different in fetus and adult. The "fetal" versus "adult" enzyme had a higher affinity for UDP-glucuronic acid, but a poorer affinity for acetaminophen. Furthermore, enzyme in fetal liver (113 days of gestation) was activated about 30% by the allosteric effector UDP-N acetylglucosamine, whereas enzyme in adult liver was activated by 500%. These differences between fetal and adult enzymes diminished just prior to parturition (141-day fetus). Enzyme in microsomes from the 141-day fetus responded to UDP-N acetylglucosamine-like enzyme in adult microsomes and had affinities for substrates that were similar to "adult" enzymes. These data indicate that maturation of the system that glucuronidates acetaminophen is a complex process. It may involve the expression in fetuses of a type of UDP-glucuronosyltransferase that is different from that expressed in the adult. An alternative but not mutually exclusive possibility is that maturation of the glucuronidation system involves modification of enzyme function by alteration of the phospholipids in the immediate environment of UDP-glucuronosyltransferase within the microsomal membrane. PMID- 3092830 TI - Effects of the chrysotherapeutic agents auranofin and gold sodium thiomalate on hepatic and renal drug metabolism and heme metabolism. AB - These studies were designed to investigate the effects of the chrysotherapeutic agents auranofin and myochrysine (GST) on hepatic and renal drug-metabolizing enzymes and heme metabolism. Male Sprague-Dawley rats were either administered a single dose of auranofin (17, 34, or 68 mg/kg, p.o.) or administered daily doses of auranofin (0.2, 0.6, 2, 9, or 40 mg/kg/day, p.o.) or GST (1.2 or 5.8 mg/kg/day, i.p.) for 3 or 14 days. Rats were killed 24 h after the final treatment, and subcellular fractions of liver and kidney were prepared. Cytochrome P-450 (P-450) content and ethoxycoumarin-O-deethylase (ECOD), benzphetamine-N-demethylase (BPND), delta-aminolevulinic acid (ALA) synthetase, and heme oxygenase activities were determined. Twenty-four hours following single doses of auranofin, no effects on hepatic P-450, ECOD, or BPND were observed. Treatment with the positive control compounds, CoCl2 (60 mg/kg) and Co protophorphyrin IX (33 mg/kg), produced decreases in all three variables at 24 hr. Auranofin, at 2 mg/kg, and GST treatment, at both doses, reduced hepatic P 450 and ECOD activity at 3 days. This effect was reversed with continued treatment for 14 days. BPND activity was unaffected at 3 days but was decreased at 14 days. Heme oxygenase activity was enhanced at 3 days and had returned to control activity at 14 days, while ALA synthetase was unaffected. With the exception of heme oxygenase, which was increased, renal variables were unaltered at 3 days. At 14 days, renal P-450 content was decreased in the high-dose auranofin group, heme oxygenase activity was increased in all groups, and ALA synthetase activity was elevated in high-dose auranofin animals. These data indicate that, at doses twenty times the human dose, auranofin and GST administration produced reversible decreases in hepatic and renal P-450 which may be the result of altered heme metabolism. PMID- 3092832 TI - Evidence for direct effect of tolbutamide on hepatic glycogenolysis induced by Ca2+-dependent hormones. AB - The effects of tolbutamide and glibenclamide on hepatic glycogenolysis in perfused rat liver were investigated. Tolbutamide per se did not influence glucose output from the liver, but at therapeutic concentrations (about 350 microM) it significantly inhibited the glycogenolysis induced by phenylephrine, vasopressin and angiotensin II, while glibenclamide did not. Neither tolbutamide nor glibenclamide inhibited the glycogenolysis induced by glucagon. Tolbutamide potentiated the inhibitory effect of submaximal concentrations of insulin on glycogenolysis induced by phenylephrine. This effect of tolbutamide was elicitable even in the absence of calcium in the perfusate, and was additive to that of trifluoperazine. However, tolbutamide did not potentiate the inhibitory effect of insulin on glucagon-induced glycogenolysis. Tolbutamide inhibited the glycogenolysis induced by A23187, a calcium ionophore. These results indicate that, in addition to its known effect on insulin secretion, tolbutamide has a direct effect on the liver to inhibit glycogenolysis induced by Ca2+-dependent hormones (catecholamines, vasopressin and angiotensin II) and A23187. Thus, it is likely that tolbutamide inhibits the effect of Ca2+ mobilized by Ca2+-dependent hormones to stimulate glycogenolysis. PMID- 3092833 TI - Evidence that amphetamine and Na+ gradient reversal increase striatal synaptosomal dopamine synthesis through carrier-mediated efflux of dopamine. AB - Amphetamine (AMPH) releases dopamine (DA) from striatal synaptosomes and concomitantly increases DA synthesis. Since AMPH may release DA through carrier mediated diffusion via reversal of the DA uptake system, the increase in DA synthesis might depend on a functioning uptake carrier. Consistent with such a mechanism, the uptake inhibitors nomifensine (NMF) and benztropine (BZT) completely prevented the AMPH-induced increase in DA synthesis at concentrations known to inhibit DA uptake. Changes in the Na+ gradient across the synaptosomal membrane also promote DA release, since DA and Na+ are cotransported by the neuronal uptake carrier. Incubation of synaptosomes in medium containing decreasing Na+ increased DA synthesis inversely proportional to Na+ over the range 128 to 20 mM. Similarly, incubations in the presence of 10(-4) M ouabain to inhibit Na+, K+-ATPase and allow intracellular accumulation of Na+ also increased DA synthesis. These changes in DA synthesis could also be prevented by BZT and were non-additive with the AMPH-induced increase in DA synthesis. However, a concentration of ouabain (10(-6) M) which by itself did not increase DA synthesis, and does not promote DA release, potentiated the AMPH-induced increase in DA synthesis. Further, the increased DA synthesis promoted by all three manipulations was only marginally dependent on the presence of Ca2+ in the incubation medium. However, at 5 and 10 mM Na+, a second component of increased DA synthesis was observed which was insensitive to BZT, but was prevented by Ca2+ removal. These results suggest that the increase in DA synthesis, and presumably DA release promoted by AMPH, lowered Na+, and ouabain, depend on the availability of the DA carrier at the internal face of the neuronal membrane and the intracellular content of Na+. The second component of increased DA synthesis which is evident at 5 and 10 mM Na+ is discussed in terms of a possible Ca2+ mediated change in DA synthesis which is independent of the DA carrier. PMID- 3092834 TI - The influence of pretreatment on the urinary metabolite profile of pseudoracemic hexobarbital. PMID- 3092835 TI - Expression of histocompatibility antigen HLA-DR by salivary gland epithelial cells in Sjogren's syndrome. AB - Recent studies have suggested that the induction of HLA-DR antigens on epithelial cells plays an important role in the pathogenesis of autoimmune endocrine exocrine disorders. We found that salivary gland epithelial cells (i.e., acinar and ductal cells) in salivary gland biopsy specimens from patients with primary Sjogren's syndrome (keratoconjunctivitis sicca) expressed high levels of HLA-DR antigen, which were detected by staining frozen tissue sections with monoclonal antibodies and immunoperoxidase technique. In contrast, salivary gland epithelial cells from normal subjects did not express this antigen. Lymphocytes eluted from the salivary gland biopsy specimens of patients who had Sjogren's syndrome produced a soluble factor that stimulated HLA-DR synthesis by a salivary gland derived cell line (Sal-1). These tissue culture supernatants contained gamma interferon, and their ability to induce HLA-DR synthesis was blocked by monoclonal anti-gamma-interferon antibody. These results demonstrate the presence of HLA-DR antigen on salivary gland epithelial cells and suggest that local production of gamma-interferon plays a role in this induction. PMID- 3092836 TI - The effect of CS-514, an inhibitor of HMG-CoA reductase, on serum lipids in healthy volunteers. AB - CS-514 is a competitive inhibitor of HMG-CoA reductase. The effect of this agent on serum lipids and lipoproteins was studied in 10 healthy normocholesterolemic male volunteers by giving 20 mg of CS-514 or placebo twice a day for 7 days under double-blind conditions. The mean total serum cholesterol level decreased by 18.6% in the CS-514 group, whereas it increased by 7.4% in the placebo group and the difference between the two groups was statistically significant (P less than 0.01). LDL cholesterol and LDL apo B values were reduced by 22.6% and 23.2%, respectively. Serum triglyceride level did not change significantly. No clinical or laboratory abnormalities were observed. PMID- 3092837 TI - Relationship between dietary proteins, their in vitro digestion products, and serum cholesterol in rats. AB - A relationship was assessed between the amino acid composition of 9 protein sources or of their in vitro digestion products and total serum cholesterol in rats. Three animal proteins (casein, beef, fish) and 6 vegetable proteins (soy, pea, peanut meal, rapeseed, oatmeal, wheat gluten) were tested. The intact protein sources were submitted to an enzymatic proteolysis according to a new in vitro digestion method. Each protein source was hydrolyzed for 30 min with pepsin at pH 1.9, then with 10 mg pancreatin at basic pH in a dialysis cell. The digestion products diffused through the dialysis membrane of the cell and were collected by a circulating sodium phosphate buffer over a 6-h period. They were likely to correspond to end products luminal in vivo digestion. The aromatic and the basic amino acids were present in higher proportions in the digestion products than in the intact protein sources, reflecting the specificity of the proteolytic enzymes. Total serum cholesterol was measured on male Sprague-Dawley rats fed cholesterol-free or cholesterol-enriched (1% cholesterol, 0.5% cholic acid) semipurified diets containing protein sources. Total serum cholesterol ranged from 70 mg/dl with the pea diet to 98 mg/dl with the peanut meal diet in rats fed cholesterol-free diets and from 163 mg/dl with the wheat gluten diet to 313 mg/dl with the casein diet in rats fed the cholesterol-enriched diets. These results suggested no specific effect of protein from animal or vegetable origin on total serum cholesterol in rats. In rats fed cholesterol-enriched diets, significant correlations were observed between total serum cholesterol and tyrosine content or leucine/isoleucine ratio of digestion products. These correlations were stronger than those observed with intact protein sources. PMID- 3092838 TI - Serum lipids of Indian physicians living in the U.S. compared to U.S.-born physicians. AB - Reports of increased susceptibility of persons from the Indian subcontinent to coronary heart disease led us to examine serum lipids and apolipoproteins in a group of physicians born in India now living in the U.S. A matched sample of U.S. born physicians working at the same institution was recruited as controls. Fasting triglyceride (TG) levels were twice as high among the Indians (174 vs 86 mg/dl, P = 0.002), total cholesterol modestly increased (193 vs 177 mg/dl, P less than or equal to 0.01) and high density lipoprotein-cholesterol (HDL-C) fraction depressed 36 vs 40 mg/dl, P = 0.006). Both TG and HDL-C were strongly determined by relative obesity in the Americans, but not among the immigrants. Calculated values of low density lipoprotein-cholesterol (LDL-C) were similar in the two groups. Apolipoprotein A-I was significantly lower in a subsample of the Indians, while Apo B was higher. Minor differences between the groups in body mass index, food frequency intake, smoking patterns, alcohol intake and exercise did not significantly influence the results. Hereditary differences in lipid metabolism may have a role in these findings, however, the delayed effects of adaptation to U.S. lifestyle cannot be ruled out. PMID- 3092839 TI - Combined heart-lung transplantation: a review. PMID- 3092840 TI - Linker polypeptides of the phycobilisome from the cyanobacterium Mastigocladus laminosus. I. Isolation and characterization of phycobiliprotein-linker polypeptide complexes. AB - Phycobilisomes from the cyanobacterium Mastigocladus laminosus cultured in white and red light were isolated and compared with respect to the phycoerythrocyanin (PEC) and linker polypeptide contents. It was verified that the production of PEC is induced by low light intensities. A PEC complex, (alpha PEC beta PEC)6LR34.5,PEC, and a phycocyanin (PC) complex, (alpha PC beta PC)6LR34.5,PC, were isolated from phycobilisomes by Cellex-D anion exchange chromatography and sucrose density gradient centrifugation. The absorption and fluorescence emission maxima of the PEC complex are at 575 and 620 nm and those of the PC complex are at 631 and 647 nm, respectively. The extinction coefficients of the two complexes were determined. From different experiments it was concluded that PEC is present as a hexameric complex, (alpha PEC beta PEC)6LR34.5,PEC, in the phycobilisome. The two linker polypeptides LR34.5,PEC and LR34.5,PC were isolated from their phycobiliprotein complexes by gel filtration on Bio-Gel P-100 in 50% formic acid. A 5-kDa terminal segment of both linker polypeptides was found to influence the hexamer formation of the phycobiliproteins. The same segments have been described to be responsible for the hexamer-hexamer linkage (Yu, M.-H. & Glazer, A.N. (1982) J. Biol. Chem. 257, 3429-3433). A 8.9-kDa linker polypeptide, LR(C)8.9, was isolated from a PEC fraction of the Cellex-D column by Bio-Gel P-100 gel filtration in 50% formic acid. Localisation of this protein within the phycobilisome was attempted. Its most probable function is to terminate the phycobilisomal rods at the end distal to the allophycocyanin core. PMID- 3092841 TI - Linker polypeptides of the phycobilisome from the cyanobacterium Mastigocladus laminosus. II. Amino-acid sequences and functions. AB - The complete primary structure of an 80-residue linker polypeptide, LR(C)8.9, from the phycobilisome of the cyanobacterium Mastigocladus laminosus was determined as well as the 44 N-terminal residues of the two linker polypeptides LR34.5,PEC and LR34.5,PC and the 114 C-terminal residues of LR34.5,PEC. A brief description of the structure determination and an extensive discussion of the relationships of these polypeptides have been published recently (Fuglistaller, P., Suter, F. & Zuber, H. (1985) Biol. Chem. Hoppe-Seyler 366, 993-1001). In this paper we report in detail about the elucidation of the primary structures. Limited digestion of the hexameric phycobiliprotein-linker polypeptide complex (alpha PEC beta PEC)6LR34.5,PEC with various proteases resulted in a linker polypeptide diminished by a 1-5 kDa segment, while the phycobiliproteins remained intact. By N-terminal sequence analysis of the residual part of the linker polypeptide in the complex, LR34.5-5,PEC, it was concluded that the C-terminus of the polypeptide had been attacked by the proteases. This C-terminal part of the protein influences the hexamer formation of phycoerythrocyanin (PEC) and is responsible for the linkage between two phycobiliprotein hexamers. From the function of the C-terminal segment of LR34.5,PEC and its homology to the LR(C)8.9 polypeptide, it was concluded that LR(C)8.9 is located at the end of the peripheral phycobilisomal rods distal to the allophycocyanin core. PMID- 3092842 TI - The complete amino-acid sequence of C-phycoerythrin from the cyanobacterium Fremyella diplosiphon. AB - The amino-acid sequences of both subunits of C-phycoerythrin from the cyanobacterium Fremyella diplosiphon have been determined. The alpha-subunit contains 164 amino acid residues, two phycoerythrobilin (PEB) chromophores and has a molecular mass of 18,368 Da (protein: 17,192 Da + 2 PEB, one PEB accounting for 588 Da). The beta-subunit consists of 184 residues, three PEB chromophores and has a molecular mass of 20,931 Da (protein: 19,168 Da and 3 PEB: 1,764 Da). The five PEB chromophores (open chain tetrapyrroles) are covalently bound to six cysteine residues (one of them doubly bound to two cysteine residues). On the alpha-subunit, the first chromophore was found at position 84, homologous to the chromophore binding site of the other biliproteins APC, PC and PEC. The second chromophore, unique for the alpha-subunit of PE, is inserted together with a pentapeptide at position 143 a. On the beta-subunit, a doubly bound chromophore is attached to cysteine residues 50 and 61, similar to the rhodophytan phycoerythrins (B-PE and R-PE). The second and third chromophores were found at positions 84 and 155, homologous to the other biliproteins. A unique peptide insertion of 14 amino acid residues (without chromophore) was found at position 141 a-o in the beta-subunit and probably is located in the three-dimensional model near the additional chromophores of the C-PE alpha- and beta-subunits. Both additional chromophores of the C-PE alpha- and beta-subunit may be located at the periphery of the C-PE-trimer. The amino-acid sequence homology between C-PE alpha and beta-subunit is 26% and to the alpha- and beta-subunits of C-PC from Mastigocladus laminosus 49% and 48%, respectively. PMID- 3092843 TI - The primary structure of Bacillus cereus neutral proteinase and comparison with thermolysin and Bacillus subtilis neutral proteinase. AB - The complete amino-acid sequence of a neutral proteinase, produced by Bacillus cereus, was determined by protein sequencing. The neutral proteinase consists of 317 amino-acid residues. The primary structure is 70% homologous to thermolysin, a thermostable neutral proteinase and 45% homologous to Bacillus subtilis neutral proteinase. The zinc-binding site and the hydrophobic pocket of the active site are highly similar in all three proteinases. B. cereus neutral proteinase which is 20 degrees C less thermostable (60 degrees C) than thermolysin (80 degrees C) shows only minor differences in calcium binding sites and salt bridges compared to thermolysin (known from its X-ray diffraction analysis), whereas B. subtilis neutral proteinase (50 degrees C) differs considerably. Therefore it was assumed that the difference in thermostability between B. cereus neutral proteinase and thermolysin is not caused by different metal binding properties, or differences in the active site, but by changes within the rest of the molecule. Calculation of secondary structure potentials according to Chou & Fasman, hydrophobicity and bulkiness of the different structural elements and preferred cold----hot amino acid residue exchanges indicated, that the thermostability of thermolysin compared to B. cereus neutral proteinase is caused by small effects contributed by numerous amino-acid exchanges distributed over the whole molecule, resulting in increased hydrophobicity of beta-pleated sheet and higher bulkiness of alpha helical regions. PMID- 3092844 TI - The treatment of thyroid cancer. The role of fine-needle aspiration cytology. AB - A series of 960 fine-needle aspiration biopsies of thyroid lesions are reported. The primary indication is the presence of a solitary thyroid mass. Aspiration biopsy is accomplished using a 23-gauge needle and a commercially available syringe pistol equipped with a 20.0-mL syringe. Sensitivity for the presence of a thyroid neoplasm, specificity for the absence of a thyroid neoplasm, predictive value of a positive diagnosis for a thyroid neoplasm, and diagnostic efficiency are all over 90% in this series. Eight percent of the aspirates were unsatisfactory. Use of fine-needle aspiration biopsy for the diagnosis of thyroid conditions reduces thyroid surgery significantly for nonneoplastic disease. It is cost-effective and essentially free of complications. PMID- 3092845 TI - [Abnormal 13C-palmitate breath test in epileptic patients treated with valproic acid]. PMID- 3092846 TI - Serum apolipoproteins AI and B and lipoproteins in middle aged men with and without previous myocardial infarction. AB - The serum high density lipoprotein (HDL) subfractions, HDL2, and HDL3, and serum apolipoprotein AI and B (apo AI and B) were evaluated as potential indicators of the risk of ischaemic heart disease in men aged less than 60 years who had previously had a myocardial infarction and in controls with a similar socioeconomic background who had no history of myocardial ischaemia. Discriminant analysis confirmed that the combination of serum cholesterol, triglycerides, and total HDL cholesterol distinguished poorly between patients and controls. The best single discriminating variable was apo B. Stepwise discriminant analysis showed that this discrimination could be improved to a small extent by combining apo B with apo AI and parental history, but nothing was gained by measurement of serum cholesterol triglycerides, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, HDL cholesterol, HDL2 or HDL3 cholesterol. Significantly more patients than controls with type IV hyperlipoproteinaemia had raised concentrations of serum apolipoprotein B, but the frequency of raised apolipoprotein B concentrations was no greater in patients with type IV hyperlipoproteinaemia than in those with normal serum lipids. The value of apo B as an indicator of cardiovascular risk should be assessed in prospective studies. PMID- 3092847 TI - Influence of glyceryl trinitrate and nifedipine on coronary sinus blood flow and global myocardial metabolism during coronary artery operation. AB - The effects of intravenous infusions of glyceryl trinitrate and nifedipine on systemic haemodynamic function, coronary haemodynamic function, and global myocardial metabolism were compared in two groups of eleven patients with unimpaired left ventricular function undergoing elective coronary artery operation who were anaesthetised with high dose fentanyl. Severe post-sternotomy hypertension developed in three patients in the glyceryl trinitrate group who were resistant to the hypotensive effect of this agent. All patients given nifedipine remained haemodynamically stable. Coronary sinus blood flow and myocardial oxygen consumption increased and coronary vascular resistance decreased after sternotomy in the nifedipine group but not in the glyceryl trinitrate group. There is no satisfactory explanation for the apparently paradoxical increase in myocardial oxygen consumption in the patients given nifedipine. This phenomenon did not appear to be associated with any detrimental effect of left ventricular function. Thus nifedipine was better than glyceryl trinitrate for the control of post-sternotomy hypertension in patients with good left ventricular function. Intravenous nifedipine is not recommended, however, for the intraoperative control of blood pressure in patients with unstable angina or impaired left ventricular function. PMID- 3092848 TI - Atracurium and its antagonism by neostigmine (plus glycopyrrolate) in patients susceptible to malignant hyperthermia. AB - Forty patients undergoing diagnostic muscle biopsy as part of investigation for malignant hyperthermia (MH) were given atracurium 0.45 +/- 0.10 mg kg-1 for muscle paralysis. The neuromuscular blockade was antagonized with neostigmine 2.4 +/- 0.4 mg given with glycopyrrolate 0.47 +/- 0.09 mg. Rectal, muscle and skin temperatures and blood lactate concentration and venous Pco2 were measured before, during and after anaesthesia. Susceptibility to MH was established by in vitro contracture tests according to the regimen of the European MH Group. Fifteen patients were susceptible to MH (MHS), 19 were MH-negative (MHN) and six were MH-equivocal (MHE). No side effects of the drugs were noted. There were no differences between the three groups of patients in any of the measurements. PMID- 3092849 TI - Clinical evaluation of a specific benzodiazepine antagonist (RO 15-1788). Studies in elderly patients after regional anaesthesia under benzodiazepine sedation. AB - The efficacy, usefulness and side effects of RO 15-1788 (RO), a specific benzodiazepine (BZD) antagonist, have been evaluated. Sixty-two patients (ASA I III, mean age 72 +/- 9 yr) scheduled for urological surgery under regional anaesthesia and BZD sedation received placebo or RO in a randomized, double-blind fashion at the end of the procedure, following sedation with midazolam. When compared with placebo, RO improved alertness and collaboration for 15 min, and suppressed anterograde amnesia for 60 min. No major side effect was noted, although five patients became anxious after administration of RO. Two cases of a paradoxical reaction to midazolam were treated successfully by RO. PMID- 3092850 TI - Extracorporeal circuit sequestration of fentanyl and alfentanil. AB - Fentanyl or alfentanil, in doses approximating to those used in clinical practice, was added to the priming fluid of an extracorporeal circuit before the institution of cardiopulmonary bypass (CPB). The concentrations of both drugs in the priming fluid were measured over a 20-min period. The concentration of fentanyl decreased at neutral or high pH values, suggesting drug adsorption to the circuit. The concentration of alfentanil was unaffected. The administration of fentanyl to the priming fluid may produce lower anaesthetic concentrations than anticipated. PMID- 3092852 TI - Transmucosal and transdermal nitroglycerin delivery systems for prevention of chronic stable angina pectoris. PMID- 3092851 TI - Effect of oral verapamil on glibenclamide stimulated insulin secretion. AB - In order to study the effect of the calcium antagonist, verapamil, on glibenclamide stimulated insulin release, nine healthy fasted male volunteers were given 5 mg oral glibenclamide with either 120 mg oral verapamil or placebo in a double-blind crossover manner 1 week apart. Blood was withdrawn at intervals for drug, hormonal and glucose estimations. Concomitant administration of verapamil resulted in higher levels of glibenclamide at each time point (P less than 0.01) suggesting that verapamil interferes with glibenclamide metabolism. However, levels of plasma glucose, C-peptide, insulin and glucagon did not differ between the verapamil and placebo studies. PMID- 3092853 TI - Mobilisation of heavy metals into the urine by CaEDTA: relation to erythrocyte and plasma concentrations and exposure indicators. AB - To investigate the effects of calcium disodium ethylenediamine tetra-acetate (CaEDTA) on the urinary excretion, erythrocyte, and plasma concentrations and exposure indicators of seven heavy metals, CaEDTA was administered by intravenous infusion to 20 workers exposed to lead, zinc, and copper. The workers' blood lead concentrations ranged from 22 to 59 micrograms/dl (mean 38 micrograms/dl (1.8 mumol/l]. The 24 hour urinary excretion of metals after CaEDTA administration (mobilisation yield) was on average 13 times the background excretion for lead, 11 times for zinc, 3.8 times for manganese, 3.4 times for cadmium, 1.3 times for copper, and 1.1 times for chromium; no significant increase was found for mercury. The mobilisation yield of lead (MPb) was significantly correlated with whole blood and erythrocyte concentrations and the urinary excretion of lead but not with its plasma concentration; similarly, the mobilisation yield of cadmium was significantly correlated with its erythrocyte concentration. In addition, MPb was significantly correlated with intra-erythrocytic enzyme delta-aminolaevulinic acid dehydratase activity and urinary coproporphyrin excretion. The relation between the mobilisation yield of heavy metals and their body burden (and toxic signs) is discussed in the light of these findings. PMID- 3092854 TI - Chemical modification of tyrosine residues in p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens: assignment in sequence and catalytic involvement. AB - p-Hydroxybenzoate hydroxylase was modified by diethyl pyrocarbonate at pH values greater than 7 and by p-diazobenzoate. Modification of the enzyme by diethyl pyrocarbonate abolishes the affinity of the enzyme for the substrate p hydroxybenzoate. Modification by p-diazobenzoate has the same effect on the enzyme. The enzyme is protected against these modifications by the effector p fluorobenzoate. The data indicate that the modification of one tyrosine residue in the active center of the enzyme is responsible for the loss of enzyme activity. This tyrosine residue has been identified by sequence studies using radioactively labeled p-diazobenzoate and was found to be most probably Tyr-222. Diethyl pyrocarbonate reacts with a tyrosine residue in the active center other than Tyr-222; the former could not be identified. Sequence studies further showed that Cys-211 is also partially modified by p-diazobenzoate. In addition, the sequence of residues 343-345 was found to be Ser-Trp-Trp instead of the tentative assignment Ser-Tyr-Trp made earlier. The results are briefly discussed on the basis of the existing three-dimensional model of the enzyme. PMID- 3092855 TI - Reassignment of the guanine-binding mode of reduced mitomycin C. AB - Mitomycin C (1) is a clinically used antitumor antibiotic that binds covalently to deoxyribonucleic acid under reductive or acidic catalysis. We have determined the structures of the adducts resulting from attack of reductively activated 1 on the dinucleoside phosphate d(GpC) to be N2-(2'' beta, 7''-diaminomitosen-1''alpha yl)-2'-deoxyguanosine (2) and its 1'' beta-isomer (3). This represents a revision of the previously reported structures for these adducts in that the mitomycin residue is linked to the N2- rather than O6-position of 2'-deoxyguanosine. This revision is the result of applying to the mitomycin case a newly developed general method that leads to unambiguous assignment of the linkage position in complex alkylated guanosines. The method as described here takes advantage of the resolution enhancement gained by calculation of the second derivatives of absorbance Fourier transform infrared spectra. In addition, we present 1H NMR data that corroborate the assigned structures of 2 and 3 and that should serve as a useful reference for future investigations into the binding of mitomycin C to DNA. The convenient synthesis of adducts 2 and 3 from deoxyguanosine and mitomycin C reported here should facilitate such investigations as well. Furthermore, we demonstrate a useful acetylation procedure for adducts and metabolites of mitomycin C that furnishes spectroscopically superior chemical derivatives (e.g., triacetates 4 and 5, derived from acetylation of adducts 2 and 3). PMID- 3092856 TI - Menadione- (2-methyl-1,4-naphthoquinone-) dependent enzymatic redox cycling and calcium release by mitochondria. AB - The results presented in this paper reveal the existence of three distinct menadione (2-methyl-1,4-naphthoquinone) reductases in mitochondria: NAD(P)H:(quinone-acceptor) oxidoreductase (D,T-diaphorase), NADPH:(quinone acceptor) oxidoreductase, and NADH:(quinone-acceptor) oxidoreductase. All three enzymes reduce menadione in a two-electron step directly to the hydroquinone form. NADH-ubiquinone oxidoreductase (NADH dehydrogenase) and NAD(P)H azoreductase do not participate significantly in menadione reduction. In mitochondrial extracts, the menadione-induced NAD(P)H oxidation occurs beyond stoichiometric reduction of the quinone and is accompanied by O2 consumption. Benzoquinone is reduced more rapidly than menadione but does not undergo redox cycling. In intact mitochondria, menadione triggers oxidation of intramitochondrial pyridine nucleotides, cyanide-insensitive O2 consumption, and a transient decrease of delta psi. In the presence of intramitochondrial Ca2+, the menadione-induced oxidation of pyridine nucleotides is accompanied by their hydrolysis, and Ca2+ is released from mitochondria. The menadione-induced Ca2+ release leaves mitochondria intact, provided excessive Ca2+ cycling is prevented. In both selenium-deficient and selenium-adequate mitochondria, menadione is equally effective in inducing oxidation of pyridine nucleotides and Ca2+ release. Thus, menadione-induced Ca2+ release is mediated predominantly by enzymatic two electron reduction of menadione, and not by H2O2 generated by menadione-dependent redox cycling. Our findings argue against D,T-diaphorase being a control device that prevents quinone-dependent oxygen toxicity in mitochondria. PMID- 3092857 TI - Study of the interaction of Escherichia coli methionyl-tRNA synthetase with tRNAfMet using chemical and enzymatic probes. AB - The accessibility of nucleotides in Escherichia coli tRNAfMet to chemical and enzymatic probes in the presence and absence of methionyl-tRNA synthetase has been investigated. Dimethyl sulfate was used to probe the reactivity of cytosine and guanosine residues. The N-3 position of the wobble anticodon base, C34, was strongly protected from methylation in the tRNA-synthetase complex. A synthetase induced conformational change in the anticodon loop was suggested by the enhanced reactivity of C32 in the presence of enzyme. Cytosine residues in the dihydrouridine loop and in the 3'-terminal CCA sequence showed little or no change in reactivity. Methylation of the N-7 position of guanosine residues G42, G52, and G70 was partially inhibited by the synthetase. Nuclease digestion of tRNAfMet with alpha-sarcin in the presence of 1-2 mM Mg2+ resulted in cleavage mainly at C71 in the acceptor stem and was strongly inhibited by synthetase. Other nuclease digestion experiments using the single strand specific nucleases RNase A and RNase T1 revealed weak protection of nucleotides in the D loop and strong protection of nucleotides in the anticodon on complex formation. The present data, together with previous structure-function studies on this system, indicate strong binding of methionyl-tRNA synthetase to the anticodon of tRNAfMet, leading to a change in the conformation of the anticodon loop and stem. We propose that this, in turn, produces more distant, and possibly relatively subtle, conformational changes in other parts of the tRNA structure that ultimately lead to proper orientation of the 3' terminus of the tRNA with respect to the active site of the enzyme. PMID- 3092858 TI - Electrorotation--a new method for investigating membrane events during thrombocyte activation. Influence of drugs and osmotic pressure. AB - The measurement of the spin of cells in rotating high-frequency electric fields ('electrorotation') make possible the investigation of dielectric membrane properties of single cells. This method was applied to membrane permeability changes accompanying thrombocyte activation and compared with light-scattering data. Describing the dielectric behavior of platelets by a single-shell model and assuming a sufficiently low membrane conductivity of 1 X 10(-7) S/m we found for nonactivated platelets a membrane capacity of 5.5 mF/m2 and the conductivity of the internal medium was estimated to be 0.12 S/m. Upon activation, the electrorotation decreased continuously, with half-times in the range of few minutes. This could be explained assuming a 500-fold increase in membrane conductivity. The application of both local anesthetics and virostatics inhibited the decrease of electrorotation, as did hypertonic osmotic pressure. In all cases this was accompanied by inhibition of platelet aggregation. Hypotonic solutions induced self-aggregation and spontaneous loss of electrorotation. It was concluded that the increase in permeability of the granule membrane is a crucial step in the release reaction and that the electrorotation method is able to detect the incorporation of the granule membranes into the plasma membrane during activation. The advantage of this electrorotation method is that it enables measurements on a single-cell level, thus avoiding interactions between platelets. PMID- 3092859 TI - Mitomycin C-induced bidirectional transcription from the colicin E1 promoter region in plasmid ColE1. AB - Treatment of a colicinogenic culture with mitomycin C induces convergent transcription from two adjacent promoters at the beginning of the colicin E1 gene. S1-mapping and primer extension assays indicate that the mitomycin C inducible transcripts correspond to colicin E1 mRNA (cea mRNA) and to a transcript, designated RNA-C, that may code for an entry exclusion function. Nucleotide sequences that strongly resemble a consensus sequence for LexA protein binding sites span the transcription start points for cea mRNA and RNA-C. These putative operator sequences overlap by one base pair and bind LexA protein (Ebina, Y., Takahara, Y., Kishi, F., Nakazawa, A. and Brent, R. (1983) J. Biol. Chem. 258, 13258-13261). The data suggest that mitomycin C-induced bidirectional transcription from the cea mRNA and RNA-C promoters is controlled by the SOS regulatory system of Escherichia coli. PMID- 3092860 TI - A quantitative assay for the detection of hepatitis B virus DNA employing a biotin-labeled DNA probe and the avidin-beta-galactosidase complex. AB - We have developed a procedure for the quantitation of specific DNA which employs nonradioisotopic probes and beta-galactosidase as a detector. The sample DNA was immobilized on a nitrocellulose filter paper. After the filter paper had been processed to hybridization with a biotinylated probe DNA, the paper was incubated with avidin-beta-galactosidase complex. The optimum ratio of avidin to biotinylated beta-galactosidase for preparation of a complex between the two was determined. The filter paper was punched. Each punched piece was put into a microtiter well and beta-galactosidase activity was measured using 4 methylumbelliferyl beta-D-galactosidase as a substrate. By this method, we were able to quantify as little as a few picograms of specific DNA. The application of this method for the quantitative assay of hepatitis B virus DNA in serum sample is also described. The sensitivity for the detection of the DNA by our method was practically comparable to that of the conventional radioisotopic method. The validity of our method for detection of the virus DNA was further supported by comparison with the serological data. PMID- 3092861 TI - The pH and redox-state dependence of the copper site in azurin from Pseudomonas aeruginosa as studied by EXAFS. AB - The EXAFS of the K-edge of copper in azurin from Pseudomonas aeruginosa has been measured in solutions of the oxidized and reduced protein, at both low and high pH. Model compounds of known molecular structure, exhibiting Cu-N and Cu-S bonds of varying length, were studied as well. The major shell of the high-pH oxidized azurin EXAFS contains contributions of two N(His) at 1.95 +/- 0.03 A, and one S(Cys) at 2.23 +/- 0.03 A. Some minor contributions from the carbon atoms of the histidine residues and the distal sulfur atom are observed in the 3-4 A region. Upon reduction a decrease is seen in amplitude of the main peak in the Fourier transform, due to a lengthening of one of the Cu-N(His) bonds (2.05 +/- 0.03 A), and a shortening of the other (1.89 +/- 0.03 A), both by approx. 0.1 A. Indications for a Cu-S(Met) bond are found in the reduced azurin data (2.70 +/- 0.05 A). However, in the oxidized protein, this bond could not be determined unambiguously, in line with results of a model compound featuring weak Cu thioether coordination. The effect of pH is only slight for both the oxidized and the reduced protein, and no significant changes in bond lengths are found upon a change of pH from 4.1 to 9.1. The relevance of these findings for the interpretation of the existing data on the redox activity of the protein is discussed. PMID- 3092862 TI - Deconjugation of glucuronides catalysed by UDPglucuronyltransferase. AB - Evidence was found for UDPglucuronyltransferase-catalysed deconjugation of p nitrophenol-, 4-methylumbelliferone- and phenolphthalein-glucuronides. The evidence is based on the following observations: 1, deconjugation is UDP dependent and the reactions show Michaels-Menten kinetics with respect to UDP and glucuronide saturability; 2, UDP-glucuronic acid was identified as reaction product; 3, all studies were done in the presence of a beta-glucuronidase inhibitor; 4, induction profiles, using 3-methylcholanthrene and phenobarbital as inducing agents, were identical for conjugation and deconjugation reactions. Optimal deconjugation rates for p-nitrophenol- and 4-methylumbelliferone glucuronides were at pH 5.1 and for phenolphthalein-glucuronide at pH 6.5. Only conjugation reactions showed latency; the corresponding deconjugation reactions were not latent. UDPglucuronyltransferase is a group of oligomeric isoenzymes with different molecular masses. The molecular masses of the isoenzyme species catalysing the forward and reverse reactions were determined by radiation inactivation analysis. The molecular masses of the isoenzyme species mediating the catalyses of deconjugation reactions were significantly smaller than those mediating catalyses of conjugation reactions: 66 +/- 4 kDa vs. 109 +/- 7 kDa for p-nitrophenol; 82 +/- 8 kDa vs. 105 +/- 6 kDa for 4-methylumbelliferone; and 74 +/- 8 kDa vs. 159 +/- 14 kDa for phenolphthalein. This suggests that for catalyses of deconjugation reactions only part of a UDPglucuronyltransferase isoenzyme is needed, whereas for forward reactions the complete isoenzymes are required. PMID- 3092863 TI - Changes of lysine reactivities of actin in complex with DNAase I. AB - The reactivities of lysines of actin in the actin-DNAase I complex were measured by the method of reductive methylation. The reactivities of lysines in the amino terminal part, lysines 18, 50, 61 and 68, decreased 50%, while those of lysines 237, 283 and 290 increased about 30%, in comparison with those in G-actin, when actin was bound to DNAase I. These results are consistent with the view that the amino-terminal region of actin is the binding site for DNAase I. In conjunction with our earlier work on the reactivities of lysines in F-actin (Lu, R.C. and Szilagyi, L. (1981) Biochemistry 20, 5914-5919), these results are also consistent with the view that DNAase I binds to actin at one of the regions that is involved in polymerization. PMID- 3092864 TI - Human factor VIII: purification from commercial factor VIII concentrate, characterization, identification and radiolabeling. AB - Human factor VIII was purified from commercial factor VIII concentrate with a 12% yield. The specific coagulant activity of purified factor VIII was 8,000 units/mg. In the presence of SDS the purified factor VIII consisted of a variety of polypeptides on polyacrylamide gels, ranging between Mr 80,000 and Mr 208,000. In the absence of SDS the purified factor VIII showed an apparent molecular weight of 270,000 upon Sephadex G200 gel-filtration. The purified factor VIII could be activated by thrombin, which resulted in the disappearance of Mr 108,000 208,000 polypeptides in favor of an Mr 92,000 polypeptide. Treatment with factor Xa also activated factor VIII, whereas treatment with activated protein C resulted in the inactivation of coagulant activity. Coagulant-active 125I-factor VIII was prepared using a lactoperoxidase radioiodination procedure. This 125I factor had the same characteristics as unlabeled factor VIII. All polypeptides could be precipitated with monoclonal antibodies directed against factor VIII. With 125I-factor VIII a pIapp of 5.7 was found in the presence of urea. PMID- 3092865 TI - Factors influencing interaction of human plasma low-density lipoproteins with discoidal complexes of apolipoprotein A-I and phosphatidylcholine. AB - The effect of plasma components on the particle size distribution and chemical composition of human plasma low-density lipoproteins (LDL) during interaction with discoidal complexes of human apolipoprotein A-I and phosphatidylcholine (PC) was investigated. Incubation (37 degrees C, 1 h and 6 h) of LDL with discoidal complexes in the presence of the plasma ultracentrifugal d greater than 1.20 g/ml fraction (activity of lecithin-cholesterol acyltransferase inhibited) produces an increase in LDL apparent particle diameter two-to six-fold greater than that observed in the absence of the plasma d greater than 1.20 g/ml fraction. In incubation mixtures of LDL and discoidal complexes, both in the presence and absence of the plasma d greater than 1.20 g/ml fraction, the extent of LDL apparent particle diameter increase is: (1) approximately three-fold greater at 6 h than at 1 h, and (2) markedly greater for LDL with initially small (22.4-24.0 nm) major components than for LDL with initially large (26.2-26.8 nm) major components. The facilitation factor in the plasma d greater than 1.20 g/ml fraction is not plasma phospholipid transfer protein. Purified human serum albumin produces an apparent particle diameter increase comparable to the plasma d greater than 1.20 g/ml fraction. The discoidal complex-induced increase in LDL apparent particle diameter value by albumin is associated with an increase in phospholipid uptake by LDL and a decreased loss of LDL unesterified cholesterol. In preliminary experiments, high-density lipoproteins (HDL) reverse the apparent particle diameter increase originally induced by discoidal complexes. The presence of HDL (HDL phospholipid/LDL phospholipid molar ratio of 10:1) in the incubation (6 h) mixture of LDL and discoidal complexes also attenuates LDL apparent particle diameter increase. In vivo, the plasma LDL/HDL ratio may be a controlling factor in determining the extent to which phospholipid uptake and the associated change in LDL particle size distribution occurs. PMID- 3092866 TI - Changes induced by PAF-acether in diacyl and ether phospholipids from guinea-pig alveolar macrophages. AB - The release and the mobilization of arachidonic acid from guinea-pig alveolar macrophages labeled with [1-14C]arachidonic acid for short (1 h) and long (18 h) periods and stimulated with PAF-acether (1-alkyl-2-acetyl-sn-glycero-3 phosphocholine) was studied. After short labeling periods arachidonic acid was primarily incorporated into alkylacyl- and diacylglycerophosphocholine (alkylacylGPC, diacylGPC) and glycerophosphoinositol (GPI), whereas after long labeling periods arachidonic acid was mainly incorporated into alkenylacylglycerophosphoethanolamine (alkenylacylGPE). In macrophages labeled for 1 h, PAF-acether (1 microM) induced a significant decrease in the amount of arachidonic acid esterified into diacyl- and alkylacylGPC and GPI, as well as a significant increase of arachidonate transferred into alkenylacylGPE. No significant decrease in arachidonate esterified in GPC fractions and in GPI was induced by PAF-acether in macrophages labeled for 18 h, whereas the increased transfer of the fatty acid into alkenylacylGPE was still measurable. This study shows that PAF-acether induces the release and the mobilization of newly incorporated arachidonic acid in alveolar macrophages. When cells are labeled for long periods and the majority of arachidonic acid is retained in ether-linked phospholipids, no PAF-acether-induced release of arachidonate was obtained, whereas its transfer was maintained. PMID- 3092867 TI - A cytosolic phospholipase in human neutrophils that hydrolyzes arachidonoyl containing phosphatidylcholine. AB - In stimulated neutrophils the production of eicosinoids and the lipid mediator, platelet-activating factor, is thought to be initiated by the activation of a phospholipase A2 which cleaves arachidonic acid from choline-containing glycerophospholipids. Accordingly, studies were undertaken in human neutrophils to characterize phospholipase enzymes that can hydrolyze 1-acyl- and 1-alkyl linked arachidonoyl-containing phosphatidylcholine (PC). Cellular homogenates were incubated with sonicated dispersions of the arachidonoyl-labeled phospholipid substrates and the hydrolysis of radiolabeled arachidonate was measured. The phospholipase activity was cytosolic, optimal at pH 8.0, and calcium dependent. The homogenization conditions used were important in determining the amount of recoverable enzymatic activity. Vigorous sonication and the presence of calcium during homogenization were strongly inhibitory, whereas the presence of EGTA, heparin and proteinase inhibitors during homogenization increased the activity. Competitive experiments with unlabeled substrates suggested that the phospholipase hydrolyzed arachidonic acid equally well from either 1-acyl- or 1-alkyl-linked PC. However, the phospholipase did show specificity for arachidonic acid, compared to oleic or linoleic acids, at the sn 2 position of 1-acyl-linked PC. When neutrophils were first stimulated with the ionophore A23187, the phospholipase activity against 1-O-hexadecyl-2 [3H]arachidonoylglycerophosphocholine (GPC) increased in a time-dependent fashion up to 3.5-fold over the unstimulated level. The activity against 1-palmitoyl-2 [3H]arachidonoyl-GPC also increased after ionophore stimulation but to a lesser extent. The results demonstrate the presence of a cytosolic, activatable phospholipase that may be involved in PC turnover, arachidonic acid release, and platelet-activating factor production in human neutrophils. PMID- 3092868 TI - Apparent in vivo retroconversion of dietary arachidonic to linoleic acid in essential fatty acid-deficient rats. AB - Essential fatty acid-deficient rats were fed ethyl [U-14C]arachidonate (308 dpm/nmol) and when a decrease in the transepidermal water loss was seen, the epidermal sphingolipids, acylglucosylceramide and acylceramide were isolated. [14C]Linoleic acid (approx. 130 dpm/nmol) was present in both lipid classes, while the substrate was only detected in the former. These results intimate that in vivo retroconversion of arachidonic to linoleic acid can be induced in the rat. PMID- 3092869 TI - Essential fatty acid uptake and esterification in primary culture of rat hepatocytes. AB - Primary cultures of adult rat hepatocytes were used to compare the uptake and esterification of essential polyunsaturated fatty acids (18:2, 20:3 and 20:4 of the n-6 series) with those of palmitic and oleic acids. The uptake of unesterified fatty acids was linearly related to the free fatty acid/albumin molar ratio for 14 h and did not depend on the unbound free fatty acid level. Whatever the initial free fatty acid/albumin molar ratio, it dropped to 0.5 +/- 0.1 mM after 14 h, thus showing that hepatocytes have a high capacity for clearing free fatty acids from the medium at high free fatty acid/albumin molar ratios. The free fatty acid uptake become saturable when the free fatty acid and albumin concentrations were raised and the free fatty acid/albumin ratio remained constant. This strongly suggests that albumin-hepatocyte interaction mediates free fatty acid uptake. This uptake was identical whatever the fatty acid tested and did not depend on the relative amounts of fatty acids when they were added simultaneously. Triacylglycerol accumulation and synthesis, monitored by labelled fatty acids, were related to the free fatty acid/albumin molar ratio and exhibited no specificity for the series of fatty acids tested. Triacylglycerols were enriched in all the fatty acids tested by up to 60%, and fatty acid incorporation into diacylglycerols and triacylglycerols reflected the free fatty acid composition of the medium. By contrast, neither the level nor the synthesis of phospholipids varied with free fatty acid/albumin, but the rate of phospholipid turnover depended on the fatty acids tested. Accumulation of these acids was smaller in phospholipids than in triacylglycerols. When linoleic and arachidonic acids were added together, phospholipids (especially phosphatidylethanolamine and phosphatidylinositol) were more enriched in arachidonic acid than triacylglycerols. This might be due to the specificity for fatty acid of the enzymes involved in phospholipid metabolism. PMID- 3092870 TI - Incorporation and redistribution of arachidonic acid in diacyl and ether phospholipids of bovine aortic endothelial cells. AB - The present experiments characterized the incorporation and redistribution of arachidonic acid in diacyl and ether phospholipids of bovine aortic endothelial cells. Confluent cultures were either continuously labeled or pulse labeled with [14C]arachidonic acid. Major lipid classes and ether-linked subclasses of phosphatidyl-ethanolamine (PE) and phosphatidylcholine (PC) were separated by high-performance liquid chromatography and thin-layer chromatography. During continuous labeling, total incorporation of arachidonic acid reached a peak at 8 h and was essentially constant up to 24 h. After 8 h, net label in total PC declined, whereas that in total PE continued to rise. In pulse labeling experiments radioactivity in diacyl PC continuously declined with concomitant increases in both diacyl- and alkenylacyl PE. The data demonstrate that transfer of arachidonic acid from diacyl PC to both diacyl- and alkenylacyl PE occurs in endothelial cells. In contrast to previous observations in platelets, transfer of arachidonic acid to alkenylacyl PE did not require agonist stimulation. This pathway may contribute to the enrichment of endothelial cell PE with arachidonic acid with the potential for subsequent metabolism to prostacyclin. PMID- 3092871 TI - Role of directional Ca2+ effect on reduced viscosities of mucus secretions from chicken trachea in vitro. AB - Reduced viscosities of fibrillar and gelatinous type mucins produced in response to high submucosal Ca2+ and low luminal Ca2+ effects were significantly higher than those of corresponding types of normal mucins. The increased reduced viscosity of experimental mucin samples was due to their aggregation with unique low molecular weight (mr 325,000 and 46,200) sulphate-rich components. The Ca2+ appeared to exert two opposing effects on viscosity properties of mucins; whereas Ca2+-dependent complexes between different types of mucins appeared to be a selective phenomenon between sulphate-rich mucins and components. Ester sulphate residue content rather than N-acetylneuraminic acid residue content of these mucins and low molecular weight components showed a very good correlation with their reduced viscosity and Ca2+-binding values. PMID- 3092872 TI - The rapid purification and partial characterization of human sperm proacrosin using an automated fast protein liquid chromatography (FPLC) system. AB - A rapid and efficient procedure was developed for obtaining highly purified human proacrosin. Ejaculated spermatozoa were washed via centrifugation through 1 M sucrose containing 50 mM benzamidine and acid-extracted in the presence of benzamidine. The solubilized material was dialyzed then lyophilized. The sample was resuspended in 8 M guanidine hydrochloride in acetic acid (0.5 M) pH 2.5 and then subjected to gel permeation chromatography with an automated fast protein liquid chromatography system utilizing two Pharmacia Superose 12 columns set in tandem that were equilibrated in the same buffer. The proacrosin eluted as an individual peak that was well separated from another proteinase zymogen referred to as sperminogen. The proacrosin preparation was determined to be highly purified when observed on silver-stained SDS-polyacrylamide gels as well as on gelatin-SDS-polyacrylamide gels. The proacrosin appeared as a doublet (Mr = 55,000 and 53,000) on both of these systems. The autoconversion of proacrosin to acrosin at pH 8 resulted in a typical sigmoidal autoactivation curve. Following protein staining of SDS-polyacrylamide gels, it was shown that upon activation of purified proacrosin preparations the 55,000 and 53,000 molecular weight proteins were initially degraded to a 49,000 form and then to several lower molecular weight forms (Mr = 40,000-34,000). Similar findings with regard to proteolytic digestion were observed following gelatin-SDS-polyacrylamide zymography except that an increase with time in proteinase intensity between 58,000 and 53,000 was also observed. Cobalt and calcium were found to be potent inhibitors of the conversion of proacrosin into acrosin, while sodium resulted in much less inhibition of this process. Calcium was found to markedly enhance the proteolytic activity of human acrosin, while it had no observable influence on the acrosin hydrolysis of benzoylarginine ethyl ester. Thus, the described purification procedure resulted in a highly purified proacrosin preparation in sufficient yields to allow for its partial characterization. PMID- 3092873 TI - Protamine increases the affinity of 3'-phosphoadenosine 5'-phosphosulfate toward a sulfotransferase from chicken embryo epiphyseal cartilage. AB - A 3' -phosphoadenosine 5' -phosphosulfate (PAPS):chondroitin sulfate sulfotransferase from chicken embryo epiphyseal cartilage, which was partially purified, exhibited a molecular mass of 150 kDa. The enzymatic sulfation of totally desulfated chondroitin was activated up to 12-fold by protamine while the sulfation of partially sulfated chondroitin was activated only 3-fold. Protamine increased the affinity of the enzyme for PAPS about 4-fold when partially desulfated chondroitin was used as sulfate acceptor. The S 0.5 for the totally desulfated chondroitin was not affected by protamine, while high PAPS concentration slightly increased the affinity of the enzyme for the same sulfate acceptor. The possible role of these substances in the regulation of the sulfation of chondroitin sulfate is discussed. PMID- 3092874 TI - Regulation of gluconeogenesis from pyruvate and lactate in the isolated perfused rat liver. AB - The effects of glucagon and the alpha-adrenergic agonist, phenylephrine, on the rate of 14CO2 production and gluconeogenesis from [1-14C]lactate and [1 14C]pyruvate were investigated in isolated perfused livers of 24-h-fasted rats. Both glucagon and phenylephrine stimulated the rate of 14CO2 production from [1 14C]lactate but not from [1-14C]pyruvate. Neither glucagon nor phenylephrine affected the activation state of the pyruvate dehydrogenase complex in perfused livers derived from 24-h-fasted rats. 3-Mercaptopicolinate, an inhibitor of the phosphoenolpyruvate carboxykinase reaction, inhibited the rates of 14CO2 production and glucose production from [1-14C]lactate by 50% and 100%, respectively. Furthermore, 3-mercaptopicolinate blocked the glucagon- and phenylephrine-stimulated 14CO2 production from [1-14C]lactate. Additionally, measurements of the specific radioactivity of glucose synthesized from [1 14C]lactate, [1-14C]pyruvate and [2-14C]pyruvate indicated that the 14C-labeled carboxyl groups of oxaloacetate synthesized from 1-14C-labeled precursors were completely randomized and pyruvate----oxaloacetate----pyruvate substrate cycle activity was minimal. The present study also demonstrates that glucagon and phenylephrine stimulation of the rate of 14CO2 production from [1-14C]lactate is a result of increased metabolic flux through the phosphoenolpyruvate carboxykinase reaction, and phenylephrine-stimulated gluconeogenesis from pyruvate is regulated at step(s) between phosphoenolpyruvate and glucose. PMID- 3092875 TI - [Microcalorimetric study of the heat denaturation of carboanhydrase B]. AB - The microcalorimetric study of heat denaturation of carbonic anhydrase B has revealed that the process of denaturation of carbonic anhydrase B is accompanied by the formation of intermolecular complexes which are disrupted at a further increase of temperature. It is shown that zinc atoms stabilize the native state and do not influence the stability of intermolecular complexes. PMID- 3092876 TI - Chemical structure of 3-carbethoxypsoralen-DNA photoadducts. AB - The enzymatic digest from salmon sperm DNA photochemically modified by the monofunctional 3-carbethoxypsoralen was analyzed by high-performance liquid chromatography. The modified nucleosides extracted from DNA were compared with model compounds obtained from irradiation in the dry state of mixtures of 3 carbethoxypsoralen with 2'-deoxyribonucleosides whose chemical structures had previously been characterized. The main photoadducts formed in DNA are two cis syn diastereoisomers formed via a C4-cycloaddition reaction involving the 4', 5' double bond of 3-carbethoxypsoralen and the 5,6 double bond of 2'-deoxythymidine. Among them, the most polar one accounts for 72%. Under the same conditions, photoadducts formed between 3-carbethoxypsoralen and 2'deoxycytidine account for less than 1%. PMID- 3092877 TI - Detection of singlet oxygen and its role in dye-sensitized photooxidation in aqueous and micellar solutions. AB - Indirect methods for the detection of singlet oxygen in dye-sensitized photooxidation based on its interception by some singlet oxygen acceptors in aqueous and micellar solutions are discussed. Mechanistic aspects and some applications of a very sensitive method using p-nitrosodimethylaniline in the presence of imidazole (RNO + imidazole method) are also treated. The technique of competition kinetics with a singlet oxygen quencher N-3 which can serve for the determination of the role of singlet oxygen is discussed as well. Such competition with tryptophan and guanosine shows that these substrates react exclusively or predominantly via the singlet oxygen mechanism in the presence of hematoporphyrin as sensitizing dye. PMID- 3092879 TI - Photosensitization of membrane components. AB - The chemical mechanisms of the photosensitized peroxidation of unsaturated fatty acids and cholesterol are reviewed and the subsequent reactions of peroxide decomposition products with biological targets such as DNA and amino acids are analyzed. The importance of protein photooxidation and cross-linking in membrane function impairment is discussed. PMID- 3092878 TI - Photosensitized reactions of nucleic acids. AB - The main effects of near-ultraviolet and visible light on cellular DNA are reviewed with emphasis on base lesions, oligonucleotide single-strand breaks and DNA-protein cross-links. Model system photosensitization reactions of DNA are also discussed. This includes photodynamic effects, menadione-mediated photooxidation, photoionization of antibiotics, the photochemistry of 5 halogenopyrimidines and urocanic acid. PMID- 3092880 TI - Photosensitization of mammalian cells by psoralens and porphyrins. AB - Because of the ability of photosensitizers to induce specific photochemical reactions in vivo, leading to cell injury and death, many such molecules have been considered as therapeutic agents. Among them two classes of sensitizers, i.e. furocoumarins (psoralens) and porphyrins, are currently used for the photochemotherapy of various skin diseases and malignant lesions. Different types of cell responses can result according to the intracellular localization of the photosensitizer and to the nature of the photochemistry induced by the chromophore which absorbs photons. In this review, the cytological aspects of photosensitization by psoralens and porphyrins will be discussed. PMID- 3092881 TI - Beta-carotene therapy for erythropoietic protoporphyria and other photosensitivity diseases. AB - This paper describes the development of the use of carotenoid pigments in the treatment of light-sensitive skin diseases. It also discusses the animal and human studies involved in determining whether carotenoids have any anti-cancer activity. The possible mechanisms of carotenoid photoprotective and anti-cancer actions are briefly discussed. PMID- 3092882 TI - [Photosensitivity in human pathology: mechanisms and clinical aspects]. AB - Photosensitivity diseases are reviewed. The pathogenesis of photodermatoses is not completely elucidated, especially because the photosensitizing agents are rarely identified. In exogenous photosensitization, the chemical agent (chromophore) is most often identified, reaching the skin either via topical contact or by systemic administration (drugs). Concepts of phototoxicity (photochemical reaction) and photo-allergy (photo-immunologic reaction) explain the clinical aspects. Dermatoses with photosensitivity are divided into three groups: photo-aggravated dermatoses (solar herpes, lupus erythematosus), photosensitivity caused by protective system defect (xeroderma pigmentosum), and photosensitivity caused by metabolic defects (porphyrias, pellagra). Idiopathic photodermatoses (unknown chromophore) are triggered by solar exposure (systemic photo-allergens would serve as mediators): 'benign estival polymorphous light eruption', polymorphous light eruptions, persistent light reactor, solar urticaria. PMID- 3092883 TI - [Spontaneous and N-nitroso-N-ethylurea-induced visible mutations in Drosophila mei-41D5 and mus(1)104D1 stocks defective for postreplication repair]. PMID- 3092884 TI - [Nature of the activity of cerebral cortical neurons in the case of their partial reversible functional isolation using EGTA iontophoresis]. AB - The EGTA iontophoresis influence on activity of 63 neurons of the rat's sensomotor cortex has been investigated. Neurons with high and low sensitivity to calcium ions decreasing level in extracellular medium have been found. A possibility of partial reversible functional isolation of neuron from neuronal net by blocking the transmitter release by EGTA has been shown. PMID- 3092885 TI - Role of thyrotropin-releasing hormone in thyroid-stimulating hormone and growth hormone regulation during postnatal maturation in female Wistar rats. AB - The role of endogenous thyrotropin-releasing hormone (TRH) in the control of pituitary thyroid-stimulating hormone (TSH) and growth hormone (GH) secretion was studied during postnatal maturation in female Wistar rats. Half of the sucklings in each litter was treated intraperitoneally with either specific rabbit antiserum against TRH or normal rabbit serum (0.1-0.3 ml according to age). All animals were decapitated after 2 h. The presence of anti-TRH activity was checked as a binding of labelled TRH with plasma of the experimental animals. Immunoneutralization of endogenous TRH resulted in a decrease of plasma TSH in 3- to 15-day-old female pups as compared to control littermates. No effect of TRH antibody injection was seen at the ages of 1, 21, 30 and 70 days despite the presence of excess antibody in the plasma. A profound effect of TRH antibody on plasma TSH was seen again at the age of 100 days. Plasma GH in the same animals exhibited a paradoxical increase after TRH immunoneutralization at the age of 5 and 8 days, a decrease was found at the age of 21 days. It was concluded that hypothalamic TRH control of TSH secretion matures early in Wistar rats. Hypothalamic secretion of TRH at the ages of 1, 21, 30, and 70 days is low and(or) its role in TSH regulation is masked by other regulating factors. TRH may play a dual role in the regulation of GH secretion during the postnatal period. PMID- 3092886 TI - The use of alternative drug therapy in nine patients with recurrent affective disorder resistant to conventional prophylaxis. PMID- 3092887 TI - Prostacyclin expression by a continuous human cell line derived from vascular endothelium. AB - Prostacyclin is primarily an endothelial cell product. It contributes to the important role of endothelium in maintaining the fluidity of blood by inhibiting platelet aggregation and by promoting vasodilation. Endothelial cells in culture tend to senesce, and the level of prostacyclin expression decreases. A permanent human cell line, EA.hy 926, derived from a fusion of primary endothelial cells with cells of a less differentiated line, has been found to sustain basal and stimulated levels of prostacyclin synthesis. PMID- 3092888 TI - The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants. AB - We describe here a test for lupus anticoagulants based on a modified Russell viper venom time (RVVT), using limiting amounts of phospholipid and venom. We have studied 29 patients with a prolonged dilute RVVT. Five of the 29 had a normal activated partial thromboplastin time and three of 14 tested by the tissue thromboplastin inhibition test were normal. In 17 of 19 patients tested, the dilute RVVT was completely normal when ionophore-treated platelets were substituted for phospholipid; the remaining two patients, both with very long phospholipid-dependent dilute RVVT's, were nearly completely normalized. The dilute RVVT is not prolonged in the presence of antibodies to factors VIII, IX, or XI. Thus, the dilute RVVT appears to be a simple, reproducible, sensitive, and relatively specific method for the detection of lupus anticoagulants. PMID- 3092889 TI - Complement proteins C5b-9 stimulate procoagulant activity through platelet prothrombinase. AB - The capacity of platelets treated with nonlytic concentrations of the C5b-9 proteins to catalyze prothrombin activation and thereby trigger clot formation has been investigated. When suspended in the presence of exogenous factors Xa and Va, gel-filtered platelets treated with purified C5b-9 proteins catalyzed prothrombin to thrombin conversion at rates up to tenfold above controls, and exceeded by up to fourfold the prothrombinase activity observed for thrombin stimulated platelets. In the absence of added factor Va, C5b-9 assembly on the platelet surface significantly shortened the lag period before prothrombinase expression that was observed for untreated platelets and increased the maximum catalytic rate of thrombin formation. A comparison with other platelet stimuli revealed that the C5b-9-induced activation of platelet prothrombinase closely paralleled the effects mediated by calcium ionophore A23187. Our data suggest that the C5b-9 proteins promote the release of platelet factor V and the assembly of the prothrombinase complex, thereby potentiating the effects of thrombin on the activation of prothrombinase. Membrane assembly of the C5b-9 proteins was also observed to markedly accelerate the rate of platelet-catalyzed plasma clotting, suggesting a direct link between C5b-9-mediated prothrombinase activation and procoagulant activity accompanying immunologic damage to the platelet. PMID- 3092890 TI - Trial of repeated low-dose aspirin in diabetic angiopathy. AB - We compared the ability of aspirin to suppress platelet aggregation and thromboxane synthesis in ten normal subjects and ten patients with diabetic angiopathy and high rate of entry of new platelets into the circulation. When single doses of 100 to 1,000 mg aspirin were ingested daily for 1 month, there were time gaps between doses in which platelets from diabetics and normals aggregated and formed thromboxane ex vivo in response to the combination of arachidonic acid plus collagen. Similar gaps were also found for diabetics, but not for normals, following four daily doses (every six hours) of 25 or 100 mg. Our data show that dose schedules of aspirin which may suffice in normals are not effective in patients with diabetic angiopathy, presumably because these patients have a high rate of entry of new platelets into the circulation. We suggest that continual suppression of platelet thromboxane synthesis and aggregation by low dose, "slow-release" preparations of aspirin would be an ideal long-term approach for the prevention of thrombosis in patients with a high rate of entry of new platelets into the circulation. PMID- 3092891 TI - Species specificity of lupus-like anticoagulants. AB - Mixing studies using activated partial thromboplastin time (APTT) technique were performed on 14 patients with lupus-like anticoagulants (LLACs) using human, equine, bovine, porcine and canine plasma. Eleven patients significantly prolonged the APTT of normal human plasma (patient/control ratio = greater than 1.15) but no patient inhibited bovine plasma. However, with one exception, equine APTT ratios were concordant with human ratios. Seven of fourteen patients also inhibited porcine plasma but in each case porcine APTT ratios were lower than their human or equine counterparts. None of five patients tested inhibited canine plasma. Collectively, these results suggest heterogeneity among LLACs at least with regard to species specificity. PMID- 3092892 TI - A pain in the pelvis. PMID- 3092893 TI - The oestrogenic effects of ethinyl oestradiol/polyoestradiol phosphate and estramustine phosphate in patients with prostatic carcinoma. A comparative study of oestrogen sensitive liver proteins, gonadotrophins and prolactin. AB - Thirty previously untreated patients with carcinoma of the prostate were prospectively randomised to one of the following treatments: ethinyl oestradiol (Etivex) combined with polyoestradiol phosphate (Estradurin); estramustine phosphate (Estracyt); bilateral orchiectomy. Oestrogenic effects were measured by blood levels of pregnancy zone protein, sex hormone binding globulin, LH, FSH and prolactin. During a follow-up period of 6 months, estramustine phosphate and ethinyl oestradiol/polyoestradiol phosphate induced comparable changes in these proteins, suggesting comparable oestrogenic effects of these two forms of treatment in patients with prostatic carcinoma. PMID- 3092894 TI - Hyperalimentation of jaundiced patients on percutaneous transhepatic biliary drainage. AB - Although percutaneous transhepatic biliary drainage (PTBD) restores hepatic and renal function in patients with obstructive jaundice, it is not certain whether it reduces the rate of complications and death after biliopancreatic surgery. We studied the possibility that the operative risks of jaundiced patients are related to malnutrition and the usefulness of hyperalimentation with PTBD to reduce the incidence of complications. Sixty-four patients with obstructive jaundice and serum bilirubin greater than 200 mumol/l were randomized into two treatment groups (n = 32) with PTBD or PTBD + hyperalimentation. Four patients were withdrawn from the latter group, two for metastatic cancer and two for complications of PTBD. Before starting hyperalimentation, the incidence of malnutrition was assessed by biochemical, immunological and anthropometric tests: malnutrition was found in 70 per cent of the patients. All the patients had good recovery of hepatic function but patients treated with PTBD alone still had high mortality (12.5 per cent) and morbidity (46.8 per cent) after biliopancreatic surgery. When hyperalimentation was provided to patients on PTBD for a period of 20 days before the operation, the incidence of complications fell to 17.8 per cent and mortality to 3.5 per cent. These results suggest that the combined use of PTBD and hyperalimentation, improving both hepatic function tests and the nutritional status of jaundiced patients, can reduce the rate of complications after biliary and pancreatic surgery. PMID- 3092895 TI - In pursuit of the perfect rabies vaccine. PMID- 3092896 TI - Why nursing education has to change. PMID- 3092897 TI - Blood transfusions and cancer: anomalies explained? PMID- 3092898 TI - Suing tobacco companies. PMID- 3092899 TI - Sialomucins at resection margin and likelihood of recurrence in colorectal carcinoma. AB - Oncogenic transformation of colonic epithelium is accompanied by changes in surface carbohydrate, notably an increased secretion of sialomucins at the expense of the normally predominant sulphomucins. In a multicentre prospective trial the correlation between the presence of sialomucins at the resection margin and the subsequent development of local recurrence was studied in 250 patients who had undergone "curative" resection for colorectal carcinoma with a mean follow up period of 14 months. Nineteen of 70 patients (27.1%) with a sialomucin predominant pattern at either resection margin developed local recurrence compared with 15 of 180 patients (8.3%) with a mixed or sulphomucin predominant pattern (p less than 0.01). Increased sialomucin staining at the resection margins was associated with reduced survival in these patients (p less than 0.01). At a mean of 14 months of follow up 153 patients (85%) were alive in the sulphomucin group and 53 patients (76%) were alive in the sialomucin group. Regression analysis predicted five year survivals of 32.8% and 18.9% for the sulphomucin and sialomucin groups respectively. Abnormal mucus production at the resection margin in patients treated for colorectal carcinoma appears to identify those with a higher risk of local recurrence and reduced survival. PMID- 3092900 TI - Subacute sclerosing panencephalitis: detection of measles virus RNA in appendix lymphoid tissue before clinical signs. AB - An appendix removed 15 days before onset of symptoms of subacute sclerosing panencephalitis was examined retrospectively for measles virus ribonucleic acid (RNA). Tissue sections hybridised in situ to a cloned measles virus probe of deoxyribonucleic acid specific for nucleocapsid protein showed that many cells of the lymphoid tissue contained measles virus RNA. In contrast, only a few infected lymphoid cells were detected in three out of six seropositive controls and none in three seronegative infants. A widespread chronic viral infection of the immune system, established after measles, may promote or even initiate nerve cell infection in subacute sclerosing panencephalitis. PMID- 3092901 TI - Respiratory symptoms and bronchial reactivity: identification of a syndrome and its relation to asthma. AB - Two postal questionnaire surveys were carried out among the adult population of Southampton aimed at clarifying the diagnostic criteria for asthma (study 1) and at testing the validity of symptoms so identified as diagnostic of bronchial hyper-reactivity (study 2). The questionnaires asked about respiratory symptoms and included three questions thought likely to disclose increased bronchial reactivity. Laboratory measurements on subsamples of respondents included spirometry and bronchial challenge with increasing doses of histamine till a concentration was reached provoking a fall of more than 20% (PC greater than 20) in forced expiratory volume in one second. In the first study no normal subject (that is, one who did not report shortness of breath or wheezing on the questionnaire) had a PC greater than 20 below 0.5 g/l. Of 51 subjects who reported shortness of breath or wheezing, or both, nine had a cluster of abnormalities consisting of one or more symptoms of bronchial irritability, nocturnal dyspnoea, and prolonged morning tightness together with PC greater than 20 values of 0.5 g/l or less. These symptoms in conjunction with a low PC greater than 20 were termed the bronchial irritability syndrome. In the second study bronchial challenge confirmed the close association of these symptoms with bronchial hyper-reactivity, all other subjects being less reactive to histamine. Only 27% of subjects with symptoms of the bronchial irritability syndrome had been diagnosed as asthmatic by their general practitioners. The bronchial irritability syndrome is a definable entity for epidemiological study and patient care. PMID- 3092902 TI - Association between transfusion of whole blood and recurrence of cancer. AB - Transfusion affects the immune response to renal transplantation and may be associated with recurrence of various human neoplasms. Data from patients with colonic, rectal, cervical, and prostate tumours showed an association between transfusion of any amount of whole blood or larger amounts of red blood cells at the time of surgery and later recurrence of cancer. Recipients of one unit of whole blood had a significantly higher incidence of recurrence (45%) than recipients of a single unit of red cells (12%) (p = 0.03). Recipients of two units of whole blood also had a higher rate of recurrence (52%) than those receiving two units of red cells (23%) (p = 0.03). Recipients of any amount of whole blood had similar recurrence rates (38-52%). Recipients of four or more units of red blood cells had a higher rate of recurrence (55%) than those receiving three or fewer units of red blood cells (20%) (p = 0.005). Mortality due to cancer in patients receiving three or fewer units of red blood cells (2%) was similar to that in patients who did not have transfusions (7%) and significantly lower than that observed in patients receiving three or fewer units of whole blood (20%) (p = 0.003). A proportional hazards risk analysis showed that transfusion of any whole blood or more than three units of red blood cells was significantly associated with earlier recurrence and death due to cancer. These data support an association between transfusion and recurrence of cancer. They also suggest that some factor present in greater amounts in whole blood, such as plasma, may contribute to the increased risk of recurrence in patients who have undergone transfusion. Until the questions raised by retrospective studies of cancer recurrence and transfusion can be answered by prospective interventional trials with washed red blood cells, red blood cells should be transfused to patients with cancer in preference to whole blood when clinically feasible. PMID- 3092903 TI - Incidence of rhesus immunisation after genetic amniocentesis. AB - Of 655 Rh negative women without anti-D antibody in their serum at genetic amniocentesis, 361 delivered a Rh positive infant. Prophylactic treatment with anti-D immunoglobulin was not given at amniocentesis. The women were followed prospectively, being given a screening test for antibody after amniocentesis, at delivery, and six months later. Five of these 361 women yielded a positive test result due to anti-D antibody. The immunisation rate after genetic amniocentesis was no higher than the spontaneous immunisation rate during pregnancy. Four women who had two amniocenteses in the same pregnancy and 34 women who had amniocentesis in two consecutive pregnancies with Rh positive fetuses were not immunised. Among six women with anti-D antibody in their serum before amniocentesis the titre of antibody increased in three. Amniocentesis may have worsened the outcome of these pregnancies. These results suggest that the risk of immunisation in Rh negative women is small. PMID- 3092905 TI - Renal cell carcinoma: blood transfusion and survival. PMID- 3092904 TI - Skin reactions to terfenadine. PMID- 3092906 TI - Haem arginate in the treatment of acute hepatic porphyrias. PMID- 3092907 TI - Adrenaline, bronchoconstriction, and asthma. PMID- 3092908 TI - Subacute hepatic necrosis induced by piroxicam. PMID- 3092909 TI - Programme for early detection of gastric cancer. PMID- 3092910 TI - Prognosis of patients discharged from a coronary care unit. PMID- 3092911 TI - Findings of a national survey of the role of general practitioners in the treatment of opiate misuse: views on treatment. AB - An important component of government policy on services for drug misusers is to encourage general practitioners to take a more active role. There are, however, some indications that general practitioners regard drug misusers as undesirable patients, although no evidence is available. As part of a wider investigation of the role of general practitioners in the treatment of opiate misuse, a questionnaire, which was sent in mid-1985 to a 5% random sample of general practitioners in England and Wales, included a section designed to elicit their views on policy and treatment connected with opiate misuse. The results showed that although most general practitioners consider opiate misuse to be a priority concern for the Health Service, they also generally regard opiate misusers as especially difficult to manage, beyond their competence to treat, and less acceptable as patients than others in need of care. General practitioners who have qualified recently were somewhat less unfavourable in their views. These findings suggest that the effective implementation of government policy will require trying to modify general practitioners' attitudes and providing support for them. PMID- 3092912 TI - General medicine in the 'eighties. AB - The general physician with or without an interest is directly responsible for the initial and continuing care in most acute medicine. Specialty interests cover the whole range of medicine but in most instances are subordinate to the claims of general medicine. Consultants in district general hospitals carry a bigger caseload in acute medicine than their colleagues in teaching hospitals, and this has implications for undergraduate and postgraduate training. The management of patients in intensive care units remains very much the task of the general physician. The general physician will continue to be an essential member of the hospital service in the foreseeable future. PMID- 3092913 TI - Bias in awarding research grants. PMID- 3092914 TI - USSR letter. Difficulties of pay policlinics. PMID- 3092915 TI - Unsuspected giardiasis as a cause of malnutrition and diarrhoea in the elderly. PMID- 3092916 TI - Obstetric anesthetic services. PMID- 3092917 TI - Child health services in the community. PMID- 3092918 TI - Informed consent. PMID- 3092919 TI - Randomised trial of preterm breech delivery. PMID- 3092920 TI - Hazards of bronchoscopy. PMID- 3092921 TI - Efficacy of a new nystatin formulation in oral candidiasis. PMID- 3092922 TI - Obese deceivers? PMID- 3092923 TI - Serial visual evoked potential recordings in Alzheimer's disease. PMID- 3092924 TI - Markers of HTLV-III in patients with end stage renal failure. PMID- 3092925 TI - Neurological complications of coronary artery bypass graft surgery. PMID- 3092926 TI - Increased risk of sudden infant death syndrome in older infants at weekends. PMID- 3092927 TI - Staying one jump ahead of resistant Staphylococcus aureus. PMID- 3092928 TI - Murdering while asleep. PMID- 3092929 TI - Skimping on care of the newborn is false economy. PMID- 3092930 TI - Obstetric ultrasound: getting good vibrations. PMID- 3092931 TI - Modern management of non-Hodgkin's lymphoma. PMID- 3092932 TI - New method for typing Staphylococcus aureus resistant to methicillin based on sulphur-35 methionine labelled proteins: its application in an outbreak. AB - Sodium dodecyl sulphate polyacrylamide gel electrophoresis of sulphur-35 methionine labelled cellular proteins of Staphylococcus aureus resistant to methicillin was used as a typing method during an outbreak on a cardiothoracic ward. This showed that the outbreak strain was indistinguishable from the epidemic strain of methicillin resistant S aureus prevalent in London. In contrast, 44 epidemiologically separate strains of S aureus gave individually distinct radiolabelled protein profiles. This method permitted rapid confirmation that an epidemic strain was responsible and indicated the need for urgent control measures. PMID- 3092933 TI - Traditional Chinese acupuncture: a potentially useful antiemetic? AB - Two consecutive studies were undertaken to evaluate the effectiveness of acupuncture as an antiemetic used in addition to premedication with opioids in patients undergoing minor gynaecological operations. In the first study 25 of the 50 patients underwent acupuncture immediately after premedication with 100 mg meptazinol, the rest receiving the drug alone, and in the second 75 patients were allocated randomly to one of three groups: a group receiving 10 mg nalbuphine and acupuncture, a group receiving premedication and dummy acupuncture, and a group receiving premedication alone. Manual needling for five minutes at the P6 acupuncture point (Neiguan) resulted in a significant reduction in perioperative nausea and vomiting in the 50 patients who underwent acupuncture compared with the 75 patients who received no acupuncture. These findings cannot be explained, but it is recommended that the use of acupuncture as an antiemetic should be explored further. PMID- 3092934 TI - Effects of social support during parturition on maternal and infant morbidity. AB - Because continuous social support during labour is a component of care in many societies but inconsistent in our own, the clinical effect of support during labour on maternal and neonatal morbidity were studied. Social support was provided by female companions. Four hundred and sixty five healthy primigravidous women were enrolled using a randomised design. Compared with 249 women undergoing labour alone 168 women who had supportive female companions throughout labour had significantly fewer perinatal complications (p less than 0.001), including caesarean sections (7% v 17%, p less than 0.01) and oxytocin augmentation (2% v 13%, p less than 0.001), and fewer infants admitted to neonatal intensive care (p less than 0.10). Of the women who had an uncomplicated labour and delivery requiring no interventions, those with a companion had a significantly shorter duration of labour (7.7 hours v 15.5 hours, p less than 0.001). This study suggests that constant human support may be of great benefit to women during labour. PMID- 3092935 TI - Sleepwalking as a symptom of bulimia. PMID- 3092937 TI - Sulphinpyrazone and the platelet serotoninergic mechanism in ischaemic heart disease. AB - A double blind study in 25 patients with ischaemic heart disease and 20 matched healthy controls examined the effect of sulphinpyrazone on the uptake of serotonin by platelets and the basal concentrations of serotonin in platelets. Uptake was measured using tritium labelled serotonin and basal concentrations estimated spectrophotofluorometrically. Serotonin uptake was significantly increased both in the patients with chronic stable angina of effort and in those with a history of myocardial infarction six months or more previously. Sulphinpyrazone reduced serotonin uptake from 94.25 (SE 8.65) to 57.86 (5.37) cpm/10(8) platelets after 24 weeks of treatment in the group with stable angina and from 137.45 (16.26) to 68.08 (8.38) cpm/10(8) platelets in the myocardial infarction group. Raised basal concentrations in the two groups were also reduced by sulphinpyrazone. Placebo had no effect on serotonin uptake or basal concentrations in either group of patients. The ability of sulphinpyrazone to inhibit uptake and reduce basal concentrations of serotonin in patients with ischaemic heart disease may be yet another mechanism through which this drug exerts its beneficial antiplatelet effect. PMID- 3092936 TI - Intermittent hypoxia in patients with unexplained polycythaemia. AB - The aetiology of polycythaemia is unclear in up to 30% of patients. Twenty patients with unexplained polycythaemia were investigated to see whether they had an intermittent hypoxic stimulus to erythropoiesis that was undetected by conventional investigations for hypoxic secondary polycythaemia. Overnight polygraphic sleep studies showed that five patients had prolonged nocturnal hypoxaemia. Their arterial oxygen saturation was below 92%, the level at which appreciable hypoxic stimulation of erythropoiesis occurs, for 26-68% of the time for which they were studied. Considerable evidence is accumulating that intermittent hypoxia is a potent stimulus to erythropoiesis, and clinicians should consider the possibility of nocturnal hypoxia in patients with unexplained polycythaemia. Appropriate investigation will lead to the correct diagnosis of polycythaemia secondary to hypoxia in some cases previously regarded as idiopathic, and treatment may then be planned accordingly. PMID- 3092939 TI - Near drowning and hypothermia mimicking severe closed head injury. PMID- 3092938 TI - Effect of biofeedback on patients' tolerance of fibreoptic bronchoscopy. PMID- 3092940 TI - Timing of disc surgery after iohexol myelography and its effect on the incidence of postoperative problems. PMID- 3092942 TI - An unusual oesophageal obstruction during nasogastric feeding. PMID- 3092943 TI - Dependence on dextromethorphan hydrobromide. PMID- 3092944 TI - A complication of capillary glucose monitoring. PMID- 3092941 TI - Ceruletide for retained biliary stones. PMID- 3092945 TI - Injuries from nail gun cartridges: a dangerous new game. PMID- 3092946 TI - Sources and patterns of referrals of oral cancer: role of general practitioners. AB - Referrals of patients with oral squamous cell carcinomas to an oral medicine clinic were assessed with regard to the sources, delays, and pattern of referrals from general medical practitioners and general dental practitioners. Slightly more patients were referred by dental practitioners than by medical practitioners, but general medical practitioners were far more likely to see advanced tumours and to request an urgent second opinion or suggest a diagnosis of malignant disease. The greatest delay overall was caused by the patients in seeking advice from their practitioner, particularly those who attended a general medical practitioner. Both groups of practitioners requested a hospital opinion within roughly a month--a reasonable interval. Subsequent delays were minimal. Delays occur mainly because the patients are slow in seeking professional advice and, in general, do not appear to have been reduced over the decade since a previous British study on referral patterns was carried out. This study emphasises the importance of educating patients about oral cancer since it is they who appear to be mainly responsible for the delays in diagnosis. The results also help to dispel the myth that general medical practitioners might be less competent at diagnosis and referral of patients with oral cancer than are dental practitioners, though we are aware of misdiagnoses from both groups. PMID- 3092947 TI - Patterns of contraceptive pill taking in an inner city practice. AB - A total of 161 patients completed a questionnaire about their pattern of taking the oral contraceptive pill. Only 28% (45) of patients were taking the pill according to the manufacturer's instructions, and in the event of the pill being missed only 26% of patients would use a sheath. A tenth of the patients believed that amenorrhoea always indicated pregnancy, but 35% believed that amenorrhoea was harmful to the body. This group did not differ in their pill taking from the remaining 65% of patients. PMID- 3092948 TI - Guidelines for selective radiological assessment of inversion ankle injuries. AB - A prospective study was performed to establish definitive guidelines for selective use of radiography in the assessment of inversion ankle injuries. Five hundred patients were included, representing 3.2% of the workload of the department during the study period. There were 379 soft tissue injuries, 56 malleolar fractures, 40 avulsion fractures, 21 fractures at the base of the fifth metatarsal, and four calcaneal fractures. Multiple logistic regression identified distal fibular tenderness, age, and ability to bear weight as the most important clinical variables in predicting important fractures (p less than 0.001). A policy of requesting x ray examination of only those patients with distal fibular tenderness or inability to bear weight or aged over 60, with a further proviso that no foot radiographs should be obtained, would produce a 60% reduction in ankle radiography in this centre without detriment to patient care. PMID- 3092949 TI - Obstetric care, social class, and maternal mortality. PMID- 3092950 TI - Late diagnosis of pituitary and parapituitary lesions causing visual failure. PMID- 3092951 TI - Recommendations on blood pressure measurement. PMID- 3092952 TI - Manpower and training. PMID- 3092953 TI - Primary hypothyroidism presenting as amenorrhoea and galactorrhoea with hyperprolactinaemia and pituitary enlargement. PMID- 3092954 TI - Neurological complications of coronary artery bypass surgery. PMID- 3092956 TI - Hazards of bronchoscopy. PMID- 3092955 TI - Cryptosporidium and diarrhoea. PMID- 3092957 TI - Management of infection in the neutropenic patient. PMID- 3092958 TI - Compliance with screening for colorectal cancer. PMID- 3092959 TI - "Homeward bound": a minimal care rehabilitation unit. PMID- 3092961 TI - Transcutaneous oxygen tension during exercise in patients with claudication. PMID- 3092960 TI - Influence of dietary linoleic acid on leucocyte sodium transport and blood pressure. PMID- 3092962 TI - Diabetic renal disease: differences between Asian and white patients. PMID- 3092963 TI - Political dissent and "sluggish" schizophrenia in the Soviet Union. PMID- 3092964 TI - A star treatment for digoxin overdose? PMID- 3092965 TI - Severe head injury: the first hour. PMID- 3092966 TI - Crisis in hospital pharmacy. PMID- 3092967 TI - Campylobacter pyloridis and associated gastritis: investigator blind, placebo controlled trial of bismuth salicylate and erythromycin ethylsuccinate. AB - An investigator blind trial was performed comparing bismuth salicylate, erythromycin ethylsuccinate, and placebo in the treatment of Campylobacter pyloridis associated gastritis in patients without peptic ulceration. Fifty patients fulfilled the study criteria. There was a strong correlation between the presence of C pyloridis and histologically confirmed gastritis. Clearance of organisms led to improvement of the gastritis. C pyloridis was cleared from 15 patients; of these, 13 had gastritis initially, which resolved in 12. Conversely, gastritis resolved in only four of 32 patients not cleared of organisms (p less than 0.0001). There was significantly greater improvement in endoscopic appearances in the patients cleared of C pyloridis compared with those whose infection persisted (p less than 0.001). In the three treatment groups organisms were cleared from 14 of 18 patients receiving the locally active bismuth salicylate, only one of 15 patients receiving erythromycin ethylsuccinate, and none of 17 patients taking placebo. These findings suggest that the ideal antimicrobial for the successful eradication of C pyloridis associated gastritis should be locally active, stable at low pH, and should penetrate gastric mucus. The resolution of gastritis and improvement in endoscopic appearances associated with clearance of C pyloridis support the view that these organisms may play a part in this condition. PMID- 3092968 TI - Ketanserin in the treatment of traumatic vasospastic disease. AB - The specific serotonin receptor blocker ketanserin was given orally to 12 patients with traumatic vasospastic disease in a double blind crossover study. The effect of treatment was assessed by measuring finger systolic pressure and rewarming time after cold provocation and by medical interview and diaries. Median (range) percentage change in finger systolic pressure after cooling was 50 (0-100)% after treatment with ketanserin compared with 0 (0-90)% after placebo. Median (range) rewarming time after cooling decreased from 320 (236-972)s with placebo to 160 (88-404)s after treatment with ketanserin. These changes were not significant. Ninety five percent confidence intervals for difference between the treatments, however, showed that finger systolic pressure may be 80% better and rewarming time 256 seconds faster after treatment with ketanserin than after placebo. The number of attacks did not differ significantly between the two treatments. Two patients had a feeling of warmth in their hands during treatment with ketanserin. The results suggest that orally administered ketanserin may improve digital circulation in patients with traumatic vasospastic disease, but larger numbers of patients are required to assess the true effect of treatment with ketanserin in this disease. PMID- 3092969 TI - Course of angina pectoris after an acute coronary event. AB - The course of postcoronary angina pectoris was examined in 555 men who had survived a first attack of myocardial infarction or unstable angina. Patients were aged less than 60 and were followed up yearly for up to 17 years. Only 25 (4.5%) had coronary artery bypass surgery. Most patients with angina were treated by nitrates alone. One year after infarction 24.1% of survivors (124/515) reported the presence of angina pectoris, and the proportions at five, 10, and 15 years were 29.9%, 30.4%, and 43.5% respectively. Seventeen years after the initial event 35.3% of the survivors had never reported postcoronary anginal symptoms. The patients who experienced anginal symptoms in the year after their coronary attack had a poorer long term survival than the group who were symptom free over the first year. These patients also had longer subsequent periods with angina, though in 41.7% angina resolved before death after a median of 2.9 years. Throughout follow up mortality during periods in which patients experienced angina was higher than in the symptom free periods. This long term follow up study of patients after a coronary event confirms that the presence or absence of angina may vary considerably over time in patients treated medically and that the presence of angina is associated with a poorer prognosis. These findings have important implications when assessing the effects of various treatment modalities on postcoronary angina, including coronary artery bypass surgery. PMID- 3092970 TI - Preventable childhood deaths in Wolverhampton. AB - A retrospective survey was undertaken of all deaths in children under 5 in the borough of Wolverhampton over the years 1976-82. Cause of death was classified in terms of preventability and possibly preventable deaths studied in more detail. Birth weight in the study group was significantly lower than that of the local population; there was no difference in ethnic origin, but there were significantly more Asian girls than Asian boys. The association between potentially preventable death and various socioeconomic indicators in the electoral wards in the borough was investigated. A significant association was found between mortality and overcrowding, lack of household amenities, unemployment, lack of car ownership, and households where the head was born in the new Commonwealth or Pakistan. PMID- 3092971 TI - Screening for squamous cervical cancer: duration of low risk after negative results of cervical cytology and its implication for screening policies. IARC Working Group on evaluation of cervical cancer screening programmes. AB - A collaborative study of screening programmes in eight countries was performed to estimate the risks of cervical cancer associated with different screening policies. Most of the data came from centrally organised screening programmes. Relative protection was higher in women who had had two or more negative results of screening tests than in those who had had only one negative smear, particularly in the first five years after the last test. There was little difference in the protection afforded by screening every year compared with every three years, but screening only once every five or 10 years offered appreciably less protection. The age of the women did not affect the sensitivity of the test or the sojourn time of the disease (the length of the detectable preclinical phase during which abnormal cytology could be picked up if a smear were taken); invasive cancer in women under 25 was rare. Centrally organised screening programmes were more effective than uncoordinated screening. Screening programmes should be aimed principally at women aged 35-60 but should start some years before the age of 35, and the intervals between screening should be three years or less. PMID- 3092972 TI - Effect of magnesium supplementation on blood pressure and electrolyte concentrations in hypertensive patients receiving long term diuretic treatment. PMID- 3092973 TI - A simple grading system to guide the prognosis after hip fracture in the elderly. PMID- 3092974 TI - Effect of milk on patients with duodenal ulcers. PMID- 3092975 TI - Family doctors: their choice of practice strategy. AB - The economic decisions taken by family doctors in one family practitioner area in the north of England were examined. There was evidence of a differential response to professional and economic incentives by a group of "high investing" practices. On five indicators of improvement in practice 32% of the practices accounted for 71% of the positive scores. Nearly all the high investing practices were in affluent areas; they were on average larger and had younger partners than the other practices. The high investing practices also faced more financial problems. There was evidence that older doctors with long lists of patients had a different strategy of income maximization. Innovation in primary care is not determined by attitude alone but also by objective factors such as age, location, and size of the practice. PMID- 3092976 TI - Randomised controlled trial of computer assisted management of hypertension in primary care. AB - The hypothesis that general practitioners would obtain better outcomes for patients with hypertension using a computer than doctors not using a computer was tested. Sixty family physicians were randomised to two treatment strategies. "Test" physicians completed a data collection form after each visit from a patient with hypertension and mailed the forms to the test centre for processing. Computer feedback on management was mailed to the doctors. This encouraged doctors to apply the "stepped care" protocol, supplied charts of diastolic blood pressure v time, and ranked patients' diastolic blood pressures by percentile. Letters were mailed to patients to remind them of appointments. "Control" doctors filled out the same data collection forms as test physicians, but neither doctors nor patients received computer feedback. Physicians who used the computer saw more patients per practice than control doctors (test 50 patients, control 40). For all patients the length of follow up was significantly longer in test practices (test 199 days, control 167), and a smaller percentage dropped out of active treatment in test practices (test 37.5%, control 42.1%). For patients with "moderate" hypertension of a baseline diastolic pressure of greater than 104 mm Hg the mean score of the last recorded pressure was below the goal of 90 mm Hg in test practices (88.5 mm Hg), but it failed to reach this goal in control practices (93.3 mm Hg). A greater average reduction of diastolic pressure was achieved in test practices (test 21.7 mm Hg, control 16.7 mm Hg). Though patients with "moderate" hypertension were better controlled in test practices than in control practices, the patients in test practices visited their doctors less often (test 13.3 visits per patient-year, control 17.4 visits). Among patients with newly detected hypertension test practices achieved a greater reduction in diastolic pressure than control practices (test 15.1 mm Hg v control 11.3 mm Hg) and more sustained control of hypertension (test 323 days per patient-year with a diastolic pressure of 90 mm Hg or less v control 259 days). PMID- 3092977 TI - Parkinson's disease: disability, review, and management. AB - Data from a descriptive study of idiopathic Parkinson's disease were analysed aimed at getting a clearer picture of the impact of the disease on the community and the help available to patients and carers. Altogether 267 patients aged 40-92 were identified, and the median duration of disease in those in whom this could be assessed was 7.2 years. Of the 267 patients, 204 (76.4%) were living in the community, 51 alone. A total of 201 patients were taking levodopa, 29 out of 102 had retired early, and 60 out of 84 (71.4%) had given up driving. Most patients had symptoms at the time of study, and signs such as bradykinesia, rigidity, impaired speech, and abnormal gait were often moderate or severe. Of 214 patients whose disease was assessed using the scoring system of Hoehn and Yahr, 78 (36.4%) had grade 4 and 23 (10.7%) grade 5 disability. Despite this, however, 105 of 265 patients (39.6%) were not subject to regular medical review and only 57 of 227 patients (25.1%) had been seen by an occupational therapist, 16 (7.0%) by a physiotherapist, and 10 (4.4%) by a speech therapist. Patients with Parkinson's disease may benefit from regular medical review and being seen by therapists. PMID- 3092978 TI - Report from the PHLS Communicable Disease Surveillance Centre. PMID- 3092979 TI - The Proteus syndrome: the Elephant Man diagnosed. AB - Sir Frederick Treves first showed Joseph Merrick, the famous Elephant Man, to the Pathological Society of London in 1884. A diagnosis of neurofibromatosis was suggested in 1909 and was widely accepted. There is no evidence, however, of cafe au lait spots or histological proof of neurofibromas. It is also clear that Joseph Merrick's manifestations were much more bizarre than those commonly seen in neurofibromatosis. Evidence indicates that Merrick suffered from the Proteus syndrome and had the following features compatible with this diagnosis: macrocephaly; hyperostosis of the skull; hypertrophy of long bones; and thickened skin and subcutaneous tissues, particularly of the hands and feet, including plantar hyperplasia, lipomas, and other unspecified subcutaneous masses. PMID- 3092981 TI - Vitamin B6 concentrations in patients with chronic liver disease and hepatocellular carcinoma. PMID- 3092980 TI - Death from interventionist radiology: a cautionary tale. PMID- 3092982 TI - Ethics of predictive testing for Huntington's chorea. PMID- 3092983 TI - Use of molar units for drugs and toxins. PMID- 3092984 TI - Diabetic renal disease: differences between Asian and white patients. PMID- 3092985 TI - Smoking, drinking and polycythemia. PMID- 3092986 TI - Does sodium restriction lower blood pressure? PMID- 3092987 TI - Incarcerated inguinal hernia in infants. PMID- 3092988 TI - Anatomy of posterior pathways in reading: a reassessment. AB - Contemporary accounts of the neurology of reading stem from Dejerine's original visual-verbal disconnection hypothesis of pure alexia. Reassessment of Dejerine's traditional formulations for posterior left hemisphere pathways in reading suggests that the occipital cortex-left angular gyrus-Wernicke's area scheme is undoubtedly oversimplified. The role of left angular gyrus cortex in reading is unsettled, and although clinically undefined, more inferior portions of the left temporal lobe may also contribute to the reading process. Nevertheless, to a surprising extent, the neuroanatomic edifice erected by Dejerine remains largely intact. PMID- 3092989 TI - Acute lithium treatment suppresses the proestrous LH surge in mice: chronic lithium leads to constant diestrus. AB - Although the therapeutic usefulness of lithium in manic-depressive psychosis is now well-established, a number of basic and clinical studies in recent years have shown that the administration of this anti-manic drug produces a wide range of adverse endocrine and metabolic effects. The present study was undertaken in order to examine (a) what effects acute lithium administration might have on the preovulatory surge of luteinizing hormone (LH) during proestrus, and (b) whether chronic lithium administration has any adverse effect on the estrous cycle in C57BL/6 mice. Acute injections of lithium on the day of proestrus (at 10.00, 16.00 and 18.00 h; LD 14:10; lights on at 05.00 h CST) at a dosage of 5 mEq/kg b. wt. led to a significant (P less than 0.01) suppression of the LH surge that normally occurs in the evening of proestrus at 21.00 h. Chronic administration of lithium, on the other hand, resulted in a complete disruption in the regularity of the estrous cycle. This was characterized by an increasing number of mice showing a continuous diestrous vaginal smear during the first week of exposure to lithium, after which all of the lithium-treated mice completely stopped cycling and entered into constant diestrus. These results represent for the first time that lithium has significant adverse effects on the reproductive function in the female, especially in regard to the proestrous LH surge and estrous cyclicity in mice. Since these adverse effects were manifested under conditions when plasma lithium concentrations were within or around the therapeutic range, our results provide important conceptual information concerning possible adverse effects of lithium on the reproductive function in the human female. PMID- 3092990 TI - Olfactory bulbectomy prevents short photoperiod-induced anestrus in female golden hamsters. AB - When female golden hamsters are maintained on a photoperiod of less than 12.5 h of light per day, they go into a pineal gland-induced anestrus in 6-10 weeks. This acyclicity is similar in certain respects to the testicular regression which occurs in male golden hamsters maintained on a short photoperiod. A recent study has indicated that pre-pubertal olfactory bulbectomy (BX) will prevent the testicular regression in adult male hamsters exposed to a short photoperiod. The present study tested the effect of pre-pubertal or adult BX on the anestrus associated with maintenance of adult female golden hamsters on short photoperiod. In Expt. 1, hamsters were pre-pubertally sham BX (SH) or BX (23-25 days of age) and then maintained on LD 14:10 or LD 6:18 for 15 weeks. In Expt. 2, hamsters were SH or BX as adults (63-65 days of age) and maintained on LD 6:18 for 13 weeks. The estrous cycles of all animals were monitored on a daily basis. In Expt. 1, all animals on LD 14:10 had regular estrous cycles for the duration of the study. Sixty percent of the SH group on LD 6:18 became anestrous, whereas 87.5% of the BX group on LD 6:18 continued having regular cycles. In Expt. 2, 80% of the SH group became anestrous while 90% of the BX group continued having regular estrous cycles. The possible mechanisms whereby BX affects the cyclicity of female hamsters is discussed. The fact that BX resulted in increased morning gonadotropin levels and ovarian weight in animals on LD 14:10, as well as in the hamsters on short photoperiod, suggests that there is a relationship between the olfactory bulb and the reproductive system that is independent of the photoperiod, in addition to more dramatic effects of olfaction on reproduction in animals on a short photoperiod. PMID- 3092991 TI - Transplants of embryonic brainstem containing the locus coeruleus into spinal cord enhance the hindlimb flexion reflex in adult rats. AB - Cell suspensions of embryonic brainstem containing the locus coeruleus were injected intervertebrally into the lumbar spinal cord of adult rats whose descending catecholamine (CA) fibers had been lesioned with intracisternal injection of 6-hydroxydopamine. Up to 1100 CA cells were found 2 and 4 months later, and these cells grew processes which produced histologically detectable reinnervation of the lumbar gray matter on the injected side of the cord. To assess the functional activity of the transplanted CA cells, the force of the hindlimb flexion reflex was measured in acute spinal rats. This reflex has been shown previously to be strongly enhanced by catecholamines. The flexion reflexes were significantly stronger in the transplanted rats than in the controls. Further, the flexion reflexes were significantly reduced by phenoxybenzamine, an alpha-adrenergic blocker, in the transplanted rats while the reflexes of controls were not significantly changed. These results demonstrate that cell suspension transplants of embryonic brainstem containing the locus coeruleus into the adult rat spinal cord survive, grow reinnervating catecholamine processes, and can affect the functional activity of the spinal cord. PMID- 3092992 TI - The distribution and function of DL-[3H]2-amino-4-phosphonobutyrate binding sites in the rat striatum. AB - The binding of the glutamate-like radioligand, DL-[3H]2-amino-4-phosphonobutyrate (DL-[3H]APB), to L-glutamate-sensitive sites in the rat striatum was investigated. A single, saturable population of binding sites, indistinguishable from that characterized previously on rat whole brain synaptic membranes, was identified. The effects of specific lesions of the striatum: decortication; striatal injection of kainic acid; and 6-hydroxydopamine injections into the substantia nigra, were also examined. Specific DL-[3H]APB binding in the striatum was elevated significantly following decortication. An increase in the number of binding sites was found to be responsible for this enhancement in binding. Lesions of the postsynaptic targets of corticostriatal fibres reduced the number of DL-[3H]APB binding sites in the striatum without affecting binding site affinity. This finding suggests that L-APB sensitive excitatory amino acid receptors are located predominantly on membranes derived from structures postsynaptic with regard to the glutamatergic innervation. The possible physiological role of these receptors was examined using an in vitro release technique. Both L-glutamate and L-APB were found to facilitate potassium evoked [3H]dopamine release from striatal slices. This finding supports the proposed existence of functional acidic amino acid receptors on dopaminergic terminals in the striatum. These receptors may play an important role in the control of motor function. PMID- 3092993 TI - Leydig cells: octopaminergic neurons in the leech. AB - Leydig cells are electrically-coupled neurons in the segmental ganglia of the leech. This study reports that they stain specifically with high concentrations (0.05 mg/ml) of the dye neutral red, and that they contain octopamine, as demonstrated by radioenzymatic assay. Individual cell bodies were pooled and found to contain 0.37 pmol octopamine/cell body, giving an approximate intracellular concentration of 7.75 mM. Leydig cell bodies contain approximately 75% of the octopamine content of a segmental ganglia. Intracellular injection of large amounts of Lucifer yellow, coupled with long diffusion times, revealed a previously-undescribed Leydig cell process. The probability that Leydig cells are octopaminergic neurosecretory cells is discussed. PMID- 3092995 TI - Segmental distribution of thyrotropin releasing hormone in rat spinal cord. AB - The segmental and laminar distribution of thyrotropin releasing hormone (TRH) was determined in the rat spinal cord using radioimmunoassay (RIA) and immunocytochemistry (ICC). Immunoreactive TRH was found in sensory, autonomic, and motor spinal columns. Dorsal horn TRH-containing fibers and cell bodies in lamina II and along the lamina II/III border were seen by ICC in all spinal cord segments. ICC showed dense TRH immunoreactivity in the sympathetic areas of the thoracic cord. Densely staining TRH-containing fibers were seen in the ventral horn of all spinal segments. RIA of whole segment extracts showed high concentrations in C6-T1 and T12-L6. Low levels were seen in C2-C4 and T5-T6. Other segments were intermediate in concentration. RIA and ICC results were comparatively evaluated. PMID- 3092994 TI - TRH and LH-RH distribution in discrete nuclei of the human hypothalamus: evidence for a left prominence of TRH. AB - Thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LH RH) have been measured by radioimmunoassay in individual human hypothalamic nuclei. A significant lateralization has been found for TRH in the ventromedial, dorsal and paraventricular nuclei, with higher concentration in the left side. In contrast LH-RH values did not differ between the left and the right side. This finding represents an additional example of cerebral specialization and the first report of lateralized peptide distribution in the human hypothalamus. PMID- 3092996 TI - [The value of animal models in space physiology]. PMID- 3092997 TI - [A model for long-term changes in synaptic efficacy based on the interaction of the acetylcholine receptor with the 43,000 dalton sub-synaptic protein]. AB - A model which accounts for changes in synaptic efficacy resistant to molecular turnover is presented. This model is based upon the hypothesis of a functional coupling between neurotransmitter receptor molecules by the subsynaptic protein of 43,000 daltons. PMID- 3092998 TI - [Metabolic activation of benzo(a)pyrene by human amniotic fluid]. AB - The in vitro activation of benzo(a)pyrene was studied in amniotic fluid from ten 4-month pregnant women. Benzo(a)pyrene monooxygenase and epoxide hydrolase activities were in the same range in amniotic fluid as in human liver. Glutathione epoxide transferase activity was markedly lower than in hepatocytes. Human amniotic fluid also catalyzed the formation of hydrocarbon metabolites mutagenic to Salmonella typhimurium TA98 (Ames system). Profiles of amniotic fluid aromatic hydrocarbons from non smokers exhibited low benzo(a)pyrene concentration (less than 0.1 ng/ml). PMID- 3092999 TI - [Demonstration of pectin-lyase in Bacillus subtilis]. AB - After a screening performed on pectinolytic micro-organisms, a strain of B. subtilis was isolated. This strain has a pectic enzyme capable of beta elimination on highly methylated pectin (degree of esterification = 85%), without the action of a pectinesterase. This activity corresponds to that of a pectin lyase. PMID- 3093000 TI - [Changes in hepatic enzyme activities of drug metabolism in rats exposed to normobaric oxygen]. AB - Exposure of adult rats to 1 ATA O2 during 55 hrs. decreased cytochrome P-450 in the homogenate supernatant of livers. Hepatic microsomal epoxide hydrolase and P nitrophenol UDP-glucuronosyltransferase activities were also decreased. Histological and ultrastructural liver studies showed tissular and cellular modifications suggestive of hepatocyte hypoxia. PMID- 3093001 TI - [Glycogen depletion produced in intrafusal nuclear bag muscle fibers by brief large-amplitude muscle stretches]. AB - The glycogen content of the three types of intrafusal muscle fibre was studied with histochemical techniques in cat muscle spindles of superficial lumbrical muscles after a very large number of brief large stretches. Zones of glycogen depletion were observed in a high proportion of nuclear bag fibres, notably in bag 1 fibres, but not in chain fibres. These observations suggest that stretching of bag fibres by itself may activate these fibres. PMID- 3093002 TI - [Use of thiopental in man. Determination of this drug and its metabolites in plasma and urine by liquid phase chromatography and mass spectrometry]. AB - Thiopental is an anaesthetic drug which is currently used for cerebral resuscitation. In this last indication the drug is administrated at high doses over a period of several days. Under clinical trials thiopental and two metabolites namely 5 ethyl-5 (1' methyl-3' hydroxy-butyl) 2 thiobarbituric acid and 5 ethyl-5 (1' methyl-3' carboxy-propyl) 2 thiobarbituric acid have been determined by high performance liquid chromatography and mass spectrometry. In human plasma high concentrations of thiopental and 5 ethyl-5 (1' methyl-3' hydroxy-butyl) 2 thiobarbituric acid and a lower concentration of 5 ethyl-5 (1' methyl-3' carboxy-propyl) 2 thiobarbituric acid have been found. In urine samples these metabolites are excreted in large and approximately equal quantities, whereas small amounts of thiopental were recovered. PMID- 3093003 TI - [The Chernobyl nuclear accident]. PMID- 3093004 TI - [Vibration of neck muscles changes the apparent position of a visual target]. AB - The discharge rate of muscle spindle afferents normally provides a precise signal of muscle length. Vibration of a muscle or its tendon induces an increase in afferent discharge which then no longer represents true muscle length; however, this increased proprioceptive input is interpreted in the central nervous system as a lengthening of the muscle. The incremented signal gives rise to illusions of displacement, or movement, of a fixed, vibrated limb. A visual target attached to such a vibrated limb also appears to move. We now report that vibration of the neck muscles influences visual localisation by inducing illusory movement of targets in visual space. Subjects were seated in a totally dark room and viewed a light-emitting diode (LED). The LED was placed at eye level approximately in the body midline at a distance of 70 cm. They held a physiotherapy vibrator in the left hand with its tip against the left side of the neck. When vibration was initiated the LED appeared to move rightward. The position of the tip of the vibrator was adjusted to produce the maximum apparent displacement to the right. In some subjects the illusion had a vertical component. Subjects maintained the vibrator in position and described the illusion when vibration began, during vibration and at its end. They reported that, initially, the target moved to the right but this displacement ceased after a second or two. The target then appeared to continue in motion without changing its position. When vibration ended the target returned to its initial position.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093005 TI - [Molecular interaction between synthetic spirobutenolides and C1 esterase normal inhibitor]. AB - Previously we have found that spirobutenolide synthetic derivatives show an inhibiting effect on C1 esterase activity. In contrast to these compounds some derivatives in the same series reveal an esterase activity when they are added to a C1 esterase preparation in presence of normal serum. The present work shows that this effect reflect an interaction with natural inhibitor C1 INH. PMID- 3093006 TI - [Increased retraction of collagen lattices by fibroblasts from patients with scleroderma]. AB - Skin fibroblasts from eight scleroderma patients were seeded in collagen lattices, and their capacity of retraction was compared to that of fibroblasts from normal volunteers. In all cases, pathological fibroblasts retracted collagen lattices earlier and more intensively than controls. This in vitro feature may be related to the cutaneous retraction which characterizes scleroderma lesions in vivo. PMID- 3093007 TI - [A high-capacity affinity gel for the purification of the testicular lutropin receptor]. AB - The lutropin (LH) receptor from porcine testes was solubilized with 1% Triton X 100. The final solution was centrifuged at 100,000 X g and the supernatant was concentrated on a PM30 Amicon membrane. The concentrate was then specifically retained on an affinity gel with human choriogonadotropin (hCG) covalently grafted by its sugar moiety. The agarose affinity gel bore adipic acid hydrazide spacer arms (6 carbon length). Prior to coupling, the subunits of hCG were crosslinked with 1-ethyl-3-(dimethylamino propyl) carbodiimide and the sialic acid residues were subjected to periodate oxidation to yield aldehyde groups which could react with the hydrazides of the gel. 90% of the receptor contained in the solution incubated with this gel was retained and eluted at pH 3.2 with a purification factor greater than 700, versus a 26% yield and a purification factor of 40 with an affinity gel bearing hCG linked through its lysine epsilon amines. PMID- 3093009 TI - [Absence of linkage between Alzheimer's disease and the HLA system]. AB - The study of a family in which multiple cases of Alzheimer's disease occurred in several generations offers the opportunity to test the genetic transmission of this disease. The HLA grouping of the members of a pedigree containing 10 affected members allowed to demonstrate that the disease is not due to a single dominant gene linked to the major histocompatibility complex. Although a more complex involvement of the major histocompatibility complex cannot be totally ruled out it is obvious that a strong linkage does not exist between Alzheimer's disease and HLA. PMID- 3093008 TI - [Conditions for the use of specific antibodies for immunohistochemical visualization of serotonin and melatonin in the pineal gland of sheep]. AB - Having prepared antisera to serotonin and to melatonin, the authors were able to show that, in the pineal gland, the behaviour of these two antisera in immunohistochemical studies differs. The antiserum raised against 5HT, actually bound to the molecule formed by condensation of formaldehyde on 5HT and therefore could be used to reveal 5HT in tissue fixed with formaldehyde. On the other hand, the anti-melatonin antiserum bound to melatonin, and could therefore be used to reveal its presence in fresh tissue. PMID- 3093010 TI - [Absence of in vivo binding of deoxyribonucleic acid to the glomerular basement membrane in C57BL/6 mice]. AB - The intraaortic injection of radiolabeled deoxyribonucleic acid (DNA) into C57BL/6 mice treated with bacterial lipopolysaccharides 48 hrs. before, induced the renal deposition of DNA, as previously reported. Autoradiographic studies of the kidneys obtained from such mice did not demonstrate a selective binding of radiolabeled DNA to the glomerular basal membrane. These results argue against the in situ formation of DNA:anti-DNA immune complexes which is a proposed mechanism in the development of tissue lesions in the course of systemic lupus erythematosus. PMID- 3093011 TI - [Isolation by binding to ultrafiltration membranes of a testicular factor limiting the number of germ cells in fetal ovary of rats in vitro]. AB - The medium used for culturing in vitro fetal or neonatal testes, when used subsequently to culture for 4 days ovaries from 13.5 day old rat fetuses, has the property of severely limiting the number of ovarian germ cells. The non dialysable factor(s) responsible for the observed effect binds to ultrafiltration membranes (Diaflo, Amicon) and can be eluted from these membranes with fresh medium added 1 M NaCl. PMID- 3093012 TI - [Development of sensitivity to glycine, GABA and beta-alanine in cultured spinal neurons]. AB - Whole cell patch-clamp recording of cultured chick spinal neurons, presumed to be motoneurons, revealed currents elicited in these cells by GABA, glycine and beta alanine, corresponding to the opening of chloride channels. During maturation, sensitivity to all three transmitters were first detected on the day 6 of culture, and appeared in most neurons by day 8. However, at all stages of development, a fraction of the cells were sensitive only to GABA; this observation supports the notion that the GABA and the glycine receptors are distinct. On the other hand, separate activation by glycine and beta-alanine was never observed, in agreement with the postulate that these amino acids bind to the same receptor. PMID- 3093013 TI - Carcinoma of the penis. AB - Most premalignant penile lesions should be completely locally excised. Giant condyloma frequently cannot be distinguished from fungating carcinoma and usually requires limited penectomy. Cancers other than epidermoid carcinomas are very rare and, except for basal cell carcinoma, have a generally poor prognosis. Prognosis of squamous cell carcinoma, however, depends on the stage of disease as determined by both local invasion and by involvement of inguinal nodes. The three year survival rates for 55 patients were: stage I, 95 percent; stage II, 67 percent; stage III, 29 percent; and stage IV, zero percent. Most primary lesions were treated by partial penectomy, and no patient developed local recurrence. There is a significant discrepancy between initial clinical and histologic staging, due to the difficulty of determining lymph node metastases. Current methods of radiation therapy indicate that it has a role for management of primary penile cancer, especially in young men with small lesions. The management of inguinal lymph nodes is still debated. Although the reliability of the sentinel node biopsy has not been established, it may be appropriate in patients with noninvasive primary lesions and no detectable inguinal metastases. The need for immediate or prophylactic lymph node dissection in patients with invasive primary tumors is controversial. Successful management depends on careful and frequent follow-up examinations, with early intervention for suspicious adenopathy. In view of the poor prognosis for advanced lymph node metastases, we prefer to use early lymph node dissection when the primary lesion is deeply invasive. Limited bilateral pelvic lymph node dissection is associated with minimal morbidity and seems to be an appropriate prelude to groin dissection. Extensive pelvic metastases are a sign of incurability and abrogate the need for groin dissection. We prefer to perform the inguinal dissection at the time of lymph node dissection through a separate curve groin incision. PMID- 3093015 TI - Helping your patients deal with questionable cancer treatments. PMID- 3093014 TI - Prostate cancer: an update. AB - As noted at the beginning, a discussion of prostate cancer yields as many questions as answers. Yet, as this review has suggested, major advances in our understanding of the nature and treatment of prostate cancer have been made in recent years. As more unified and rational approaches to treatment emerge, some of the marked diversity in attitudes toward prostate cancer may lessen, and the controversies about management that characterize our present state of knowledge may abate. Carefully designed studies involving larger numbers of accurately staged and stratified patients are necessary to determine preferred treatment approaches for a disease that has such a tremendous impact on the health and well being of so many. PMID- 3093016 TI - Role of progesterone receptors in breast cancer. AB - It has been demonstrated that progesterone receptors (PRs) are at least as valuable as estrogen receptors (ERs) for predicting outcome in breast cancer patients. Retrospective analysis indicates that the presence of PRs may be the second most critical factor, after the number of positive nodes, in predicting disease-free survival, with a correlation between length of survival and number of tumor PRs. The presence of PRs has been shown to be of value for predicting response in both early and advanced breast cancer patients. In studies of assay consistency, major discordance rates were minimal in simultaneous assays, but extremely high in sequential assays of tumors that were PR-positive in initial assay. The responsible factor was interim endocrine therapy, and it was subsequently determined that the prognosis was worse for those patients whose tumors lost PR between assays. PMID- 3093017 TI - National Institutes of Health Consensus Development Conference statement: health implications of smokeless tobacco use. January 13-15, 1986. PMID- 3093018 TI - Flexible office hours. PMID- 3093019 TI - Screening the "well elderly". PMID- 3093020 TI - Cell-specific radiation dosimetry in the skeleton. PMID- 3093021 TI - Is postmenopausal bone loss an age-related phenomenon? AB - Forearm bone mineral content (BMC), an index of skeletal mineralization, and lean body mass (LBM), an index of the muscle mass in the body, were calculated in 574 healthy, white subjects, aged 20-89 years. In women, there was no significant change in BMC with age until the menopause. Thereafter, a significant decline averaging 15% per decade was found up to the age of 70 years, after which it was 10% per decade. In men, there was a significant overall decline of about 4% per decade from the age of 20. When BMC was corrected for LBM, the age-related fall in men disappeared, while remaining without a significant trend in premenopausal women. This was, however, not the case in women after the menopause, where a significant decline of about 12% per decade was noted. These data clearly demonstrate that the major contribution to the well-known bone loss in postmenopausal women is not a simple age-related phenomenon. The development of osteoporosis must be due to some additional bone-diminishing effect on the female skeleton, most likely the absence of estrogen. PMID- 3093022 TI - Does 24R,25(OH)2-vitamin D3 prevent postmenopausal bone loss? AB - The effect of oral 24R,25(OH)2-vitamin D3 as a prophylactic for postmenopausal bone loss was examined. Fifty-eight healthy, early postmenopausal women entered a double blind therapeutic trial for 2 years. After an initial examination the women were randomized to treatment with 10 micrograms 24R,25(OH)2D3 daily or placebo. Participants were thereafter examined every 3 months (nine examinations in all). In both groups the forearm bone mineral (measured by single photon absorptiometry), the lumbar spine mineral, and the total body mineral (measured by dual photon absorptiometry) fell significantly and at the same magnitude. Furthermore, serum calcium, serum alkaline phosphatase concentration, and fasting urinary hydroxyproline were unchanged, as were the 24-hour urinary calcium excretion and the intestinal radiocalcium absorption. Our findings demonstrate that 24R,25(OH)2D3 treatment has no prophylactic effect on postmenopausal bone loss and does not alter calcium metabolic variables. PMID- 3093024 TI - The effect of endogenous estrogen fluctuation on metabolism of 25-hydroxyvitamin D. AB - To test the hypothesis that estrogen modulates the metabolism of 25 hydroxyvitamin D (25(OH)D) to 1,25-dihydroxyvitamin D (1,25(OH)2D) and 24,25 dihydroxyvitamin D (24,25(OH)2D), we studied 20 normal premenopausal women at four consecutive weekly intervals during one menstrual cycle. Estrogen stimulation was semiquantitatively defined into baseline, low-grade, or medium grade categories, based on endogenous estrone and estradiol concentrations. 1,25(OH)2D increased incrementally from baseline levels of 34 +/- 3(SE) pg/ml to 39 +/- 3 pg/ml (P = 0.2) with low-grade estrogen stimulation and to 43 +/- 3 pg/ml (P less than 0.05) with medium-grade estrogen stimulation, while 25(OH)D, 24,25(OH)2D, vitamin D binding protein, parathyroid hormone, calcium, and phosphate did not change. 24,25(OH)2D was correlated to 25(OH)D at baseline (r = 0.65, P less than 0.01) and with low-grade estrogen stimulation (r = 0.62, P less than 0.01), but not with medium-grade stimulation (r = 0.13); these relationships are consistent with the concepts that 25(OH)D is metabolized predominantly to 24,25(OH)2D at low estrogen levels, but not at higher estrogen levels. We conclude that endogenous estrogen elevation promotes formation of 1,25(OH)2D from 25(OH)D, and that it may reciprocally inhibit synthesis of 24,25(OH)2D. PMID- 3093023 TI - Longitudinal changes in bone mass after one year as measured by different techniques in patients with osteoporosis. AB - Bone mass was measured in 49 postmenopausal women by the following techniques: single photon absorptiometry at the radius (SPA), dual photon absorptiometry at the lumbar spine (DPA), quantitative computed tomography at the lumbar spine with an area of interest of only trabecular bone (QCT) or of an integrated cross section of the vertebral body (QCTi), and total body calcium by neutron activation analysis (TBCa). Each women had two measurements with a one-year interval. Half of them were treated with calcium supplementation only; the other half also received calcitriol (1,25 dihydroxycholecalciferol). The aim of this report was to compare the changes of bone mass as measured by the different techniques. The DPA and QCTi values were significantly lower at one year than at baseline (by paired t-tests). The mean percent changes (+/- SD) for the measurements were: TBC, -0.4 +/- 4.6%; SPA-1, 1.2 +/- 7.1%; SPA-2, 0.7 +/- 6.0%; DPA, -2.5 +/- 11%; QCT, 6.5 +/- 23%; and QCTi, -6.0 +/- 9%. The percent changes by one technique did not show significant correlation to the percent changes by the other methods. We conclude that the precision of the methods in this clinical setting is not sufficient to show correlations after only one year; in addition, there may have been different rates of changes at different sites of the skeleton. PMID- 3093025 TI - Total body calcium measurements using neutron-activation analysis in Cushing's syndrome. AB - Total body calcium content (TBCa) was estimated by in vivo neutron activation analysis in 16 patients (14 female, 2 male) with active Cushing's syndrome, pituitary driven in all but two cases. Apart from being nonreproductive, patients were unselected. TBCa was below the predicted young normal value in all patients (mean +/- SD, 85.2 +/- 5.8% of predicted, P less than 0.01 vs. predicted) and in 13 of the 16 patients, was also below the predicted value when allowance was made for expected postmenopausal skeletal losses (mean +/- SD, 92.7 +/- 12.5% of predicted, P less than 0.02). However, individual values of TBCa were significantly lower (P less than or equal to 0.05) than the predicted normal range, corrected for postmenopausal losses, in only 3 patients (19% of the group). Initial TBCa apparently was not related to duration of the disease or to current urinary-free cortisol levels. At presentation, radiographic signs of significant osteoporosis (multiple vertebral and/or rib fractures) were present in four patients, three of whom had subnormal or borderline TBCa compared with the young normal predicted range. TBCa measurements were repeated in 9 patients 1 10 years after successful treatment, and were generally unchanged. During this period, only one vertebral fracture (consistent with simple postmenopausal osteoporosis) appeared in these patients. We conclude that bone mass tends to be low in newly diagnosed Cushing's syndrome, but that significant reduction beyond expected postmenopausal losses is relatively uncommon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093026 TI - Saturation of human salivary secretions with respect to calcite and inhibition of calcium carbonate precipitation by salivary constituents. AB - The state of saturation of human salivary secretions with respect to calcite has been investigated. This property cannot be calculated exactly because of uncertainties in the values of the solubility product constant of calcite, the dissociation constants of carbonic acid, and PCO2 values of saliva. Minimum and maximum limits for this saturation, however, can be established using appropriate values for the constants and salivary PCO2. Values that give the minimum degree of saturation show that 8 of the 70 samples of human saliva investigated would be supersaturated with respect to calcite, while 64 of the 70 samples appeared to be supersaturated when values giving the maximum degree of saturation were used. In the latter case, the ratio of ionic activity products to solubility product was above 10 for several samples and over 18 for the most supersaturated sample. Since these results show that supersaturation of saliva with respect to calcite may be a common condition, human salivary secretions were investigated for the presence of inhibitors of calcite precipitation. Inorganic phosphate and the acidic proline-rich proteins, known to be inhibitors of calcite precipitation, and human salivary statherin, now shown to have a similar activity, are present in saliva at concentrations considerably higher than those required to inhibit calcite precipitation under salivary conditions. Quantitatively, phosphate is by far the most important inhibitor of calcite precipitation present in saliva, suggesting that inhibition of calcite precipitation by the macromolecules may be of secondary significance. It seems more likely that the function of these molecules is to inhibit precipitation of calcium phosphate salts, as previously proposed. These different inhibitory activities, however, are likely to be factors in the differences in composition of oral and dental calculi in different species, and may need to be considered in the formation of calcite stones in the pancreas. PMID- 3093027 TI - Identification of osteoclasts by rhodamine-conjugated peanut agglutinin. AB - Rhodamine-conjugated Arachis hypogaea (peanut agglutinin, PNA) lectin, which is specific for beta-D-galactosyl and beta-D-gal-[1,3]-D-galNAC residues, was used to identify osteoclasts in paraffin-embedded bone sections of fetal rat calvaria and a human bone-derived tumor, osteoclastoma. All multinucleated osteoclasts were positive for PNA-lectin. This was also confirmed by studying smears of isolated osteoclasts from rat and chicken long bones. In addition to multinuclear cells, some mononuclear cells on the endosteal surface of the rat calvaria and some bone marrow cells also revealed specific binding of PNA lectin. Isolated rat peripheral monocytes were also studied, and these showed specific binding of PNA lectin which was maintained unchanged for at least 3 days in culture. Different lectins could be useful as membrane markers for studying bone cell origin and maturation. PMID- 3093028 TI - Preliminary studies of the secondary structure in solution of two phosphoproteins of chicken bone matrix by circular dichroism and fourier transform-infrared spectroscopy. AB - The secondary structures of two phosphoproteins from chicken bone matrix of Mr approximately 15kDa and approximately 28kDa, rich in Asx, Glx, and Ser, and containing Ser(P) and Thr(P) residues, have been investigated in solution by Circular Dichroism (CD) and Fourier Transform-Infrared Spectroscopy (FT-IR). CD spectroscopy, which yields useful information on the backbone conformation of polypeptides and proteins, suggests a predominantly beta-sheet structure for the two phosphoproteins. The FT-IR spectra of the approximately 15kDa protein, which is sensitive to secondary structure and hence provides complimentary information to CD spectroscopy, are consistent with the results obtained by CD studies. PMID- 3093029 TI - Changes in cartilage proteoglycans associated with calcification. AB - The purposes of these experiments were to study the biosynthetic and postbiosynthetic relationships between proteoglycans in noncalcified growth cartilage and calcified cartilage in metaphysis from the costochondral junctions of immature rabbits. Based on in vivo experiments in which 35 S-sodium sulfate was injected into rabbits, it is shown that proteoglycans from the hypertrophic region becomes part of the calcified cartilage matrix which is to be incorporated into the metaphysis. The proteoglycan aggregates in the growth apparatus undergo partial disaggregation and degradation. There is approximately a 25% decrease in aggregation from regions of the rib distal to the metaphyseal-growth plate junction (69%) to the region proximal to it (50%). In contrast, in their final state in calcified cartilage, the proteoglycans are more completely disaggregated and the proteoglycans subunits are smaller, as adjudged from gel chromatography. Control experiments indicate that although some artifactual disaggregation is produced by the extraction process, it is not of the same magnitude as that seen in the actual isolation experiments nor are the subunits reduced in size. PMID- 3093030 TI - Developmental pattern of alkaline phosphatase in soluble and particulate fractions of rat skull cap and femur. AB - Alkaline phosphatase is detected in both soluble and particulate fractions of rat bone. The concentration of alkaline phosphatase in the particulate fraction of rat skull cap bone and femur is high during the peak period of calcification of these bones suggesting the possibility of using it as a marker for the rate of bone calcification. PMID- 3093031 TI - Effects of prostaglandins on regional remodeling changes during tibial healing in beagles: a histomorphometric study. AB - A histomorphometric study was carried out on bone samples in the region of healing defects in the tibias of beagles of various ages. A 5 mm diameter drill hole defect was made in the mid-shaft of the tibia. Eleven of the beagles received either vehicle (n = 6) or prostaglandin E2 orally (n = 5) for the 30-day period from surgery to time of necropsy. Ten dogs received local injections of vehicle (n = 4) or prostaglandin E1 directly into the defects for the first 10 days after surgery. Double labels were given with each of two fluochrome markers, calcein prior to surgical treatment, and oxytetracycline hydrochloride prior to 30-day sacrifice. The regional remodeling changes were evaluated in 40-50 micron thick cross-sections taken 2 cm proximal to the defect and matching samples from the contralateral side. In the controls, the changes were variable and reflected primarily increased formation on the surfaces of the cortex. Cortical endosteal bone formation, as indicated by oxytetracycline labeling, was increased in both control groups and there was an increase in labeling in the periosteal and haversian envelopes as well, in the local injection control group. In the dogs given prostaglandin E2 orally, there was increased periosteal bone formation in addition to increased cortical-endosteal formation. When healing sides were compared to controls, prostaglandin E2-treated dogs also had increased osteoid formation in all three envelopes and increased resorption surface in the cortical endosteal envelope, indicating accelerated remodeling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093032 TI - Effects of ovariectomy on iliac trabecular bone in baboons (Papio anubis). AB - Biopsies were collected from the left iliac crest of six adult female baboons, after which three of the animals were ovariectomized. Biopsies were collected from the right iliac crest six months later. Histomorphometric evaluation of the biopsies revealed consistent increases in fractional forming surface, appositional rate, and volume-based bone formation rate after ovariectomy. The data indicate that bone turnover is increased following ovariectomy in the baboon. PMID- 3093033 TI - Treatment of psoriasis vulgaris by oral administration of 1 alpha-hydroxyvitamin D3--open-design study. AB - In an open-design study 1 alpha-hydroxyvitamin D3 was administered orally to 17 patients with psoriasis vulgaris at a dose of 1.0 micrograms/day for 6 months. More than moderate improvement was observed in 13 (76%) of the 17 patients from 2.7 +/- 0.6 months (mean +/- SD) after the start of treatment. No side effects of the treatment were observed. The mechanism of the effect of 1 alpha hydroxyvitamin D3 requires study, but these data suggest that its oral administration is effective for treatment of psoriasis vulgaris. PMID- 3093035 TI - Angiographic determination of disease-produced alterations of vasomotor tone in large coronary arteries. AB - Quantitative coronary arteriography was done before and after ergonovine and/or nitroglycerin in 24 patients. After nitroglycerin there was an average 18.6 +/- 3.9% increase in diameter of normal vessels over 2 mm in diameter, and a similar 19.3 +/- 8.7% increase in diameter of the same sized, normal appearing segments in subjects with coronary disease. In individual cases the luminal response to the drug was significantly more variable in "normal" segments of diseased vessels than in entirely normal arteries. Twenty-eight of thirty seven coronary stenoses dilated an average of 18 +/- 10.8% (range 3 to 43%) after nitroglycerin. Unequal dilation of stenosis and normal reference segment caused a 10% or greater change in calculated percent diameter stenosis in 16 lesions. Because they dilated less than would be predicted using a hypothetical geometric model to assess vessel reactivity, most of the lesions could be considered hyporeactive. Ergonovine predictably constricted normal coronary vessels in a relatively uniform fashion. Response of diseased arterial segments was more variable in a limited number of observations. Ergonovine partially antagonized the vasodilating effect of subsequently administered nitroglycerin, and larger than average or intracoronary doses of nitroglycerin had to be used to achieve the same degree of dilation seen with smaller doses in the absence of ergonovine. Disease of large coronary arteries focally alters their vasomotor tone and reactivity as gauged by responsiveness to nitroglycerin and ergonovine. Some implications of this are discussed. PMID- 3093034 TI - Metabolic rates in normal and infarcted myocardium. AB - The effects of myocardial infarction in rat hearts on the utilization of fatty acids and glucose by the surviving, non-infarcted tissue were studied. Hearts were removed from the animals one-week post-infarcted and perfused in the isolated working heart preparation. Oxygen consumption and oxidation of palmitate and glucose were determined at two levels of cardiac work. Rates of substrate oxidation were estimated by 14CO2 production from [14C]-labeled substrates. This approach to measuring metabolic rates may seriously under-estimate the true oxidative rate particularly when measuring oxidation of long-chain fatty acids. Because of the large endogenous stores of fatty acids in tissue lipids, the [14C] specific activity of the intracellular metabolites involved in the free fatty acids oxidation pathway do not equilibrate with the specific activity of the perfusate fatty acids oxidation pathway do not equilibrate with the specific activity of the perfusate fatty acid even when 14CO2 production has reached an apparent steady state. When comparing an experimental condition to the normal heart, a lower rate of 14CO2 production may not necessarily indicate a lower rate of oxidation of free fatty acids, but a difference in the rate of turnover of endogenous sources of unlabeled fatty acid such that the specific activity of intracellular metabolites equilibrate with extracellular labeled substrate to a lesser extent than in the normal heart. At physiological concentrations of fatty acids, a shift from fatty acid to carbohydrate oxidation occurred in the hypertrophied, surviving tissue following myocardial infarction in the rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093036 TI - Is the change in intracellular pH during fatigue large enough to be the main cause of fatigue? AB - The intracellular pH of frog sartorius muscles exposed to an extracellular pH 8.0 (25 mM HCO3-, 1% CO2) was 6.9-7.1. Following a fatiguing stimulation period (one tetanic contraction per second for 3 min), the intracellular pH was 6.5-6.7. When similar experiments were repeated with frog sartorius muscles exposed to pH 6.4 (2mM HCO3-, 1% CO2), the intracellular pH was 6.8-6.9 at rest and 6.3-6.4 following fatigue. So, in both experiments the intracellular pH decreased by 0.4 0.5 pH unit during fatigue. When the CO2 concentration of the bathing solution was increased from 1 to 30%, the intracellular pH of resting muscles decreased from 7.0 to 6.2-6.3. Although the effect of CO2 on the intracellular pH was greater than the fatigue effect, the decrease in tetanic force with CO2 was less than 40%, while during fatigue the tetanic force decreased by at least 70%. Therefore in frog sartorius muscle the decrease in tetanic force during fatigue exceeds the decrease that is expected from just a change in intracellular pH. PMID- 3093037 TI - Percutaneous endoscopic gastrostomy: indications and results. AB - Patients requiring feeding gastrostomies are often poor risks for either laparotomy or general anesthesia. Percutaneous endoscopic gastrostomy can be performed at the bedside by a surgeon-endoscopist and with minimal sedation. The authors performed this procedure on 45 patients ranging in age from 17 to 88 years. The procedure was indicated for neurologic disorders in 34 patients, head and neck tumours in 2, failure to thrive in 4, esophageal obstruction from lung cancer in 1 and tracheostomy for multisystem failure or trauma and sepsis in 4. In three cases the procedure could not be performed because the stomach could not be intubated. In 29 cases local anesthesia and sedation (diazepam and meperidine) were used, but in 16 cases general anesthesia with hyperventilation was preferred. The mean operative time was 32 minutes, decreasing with experience so that the current mean operative time for the last nine cases was 23 minutes. Feeding was begun on day 1 after operation in most patients and on day 2 in others. Complications included tube displacement in three patients, superficial infection at the site of the tube insertion in three (not requiring drainage or tube removal) and asymptomatic pneumoperitoneum in one patient. These complications all occurred early in the series. No patient suffered paralytic ileus, vomiting, aspiration or significant leaking around the tube. In the authors' opinion percutaneous endoscopic gastrostomy is the preferred method for placement of a feeding gastrostomy. It can be performed rapidly with minimal stress in high-risk patients. PMID- 3093038 TI - Management of primary acute arterial occlusion. AB - The management of primary acute arterial occlusion depends upon distinguishing between embolism and thrombosis. Emboli are sudden in onset, have a demonstrable source and lodge most frequently at the common femoral bifurcation. Embolectomy is the treatment of choice. Acute thrombosis is usually preceded by prolonged, progressive, ischemia, is less abrupt in onset and occurs most commonly in the superficial femoral artery. The initial treatment is anticoagulation with heparin, followed by artery repair if indicated. Emergency surgical reconstruction is necessary if the condition of the limb deteriorates despite heparin therapy. Nonviable limbs are best amputated early, and ischemic myositis is the best clinical predictor of viability. The use of streptokinase intra arterially is a reasonable alternative in patients with thrombosis, although the selection of patients is difficult. It must be followed by treatment of the underlying lesion, using either balloon angioplasty or surgical repair. PMID- 3093040 TI - Milk progesterone concentrations following simultaneous administration of buserelin and cloprostenol in cattle with normal corpora lutea. AB - Fifty Holstein dairy cows with palpable corpora lutea were divided into two groups. Twenty-five cows were given 500 micrograms of cloprostenol followed by 8 micrograms (2 mL) of buserelin, an analogue of gonadotropin-releasing hormone, and 25 were given cloprostenol followed by saline. Milk was collected for progesterone assay at the time of treatment and two days later. Differences in median progesterone concentrations before and following treatment were not significantly different between the saline and buserelin treated cows (p greater than 0.23). PMID- 3093041 TI - Cost control in the health care industry: can there be a Canadian way? PMID- 3093039 TI - The effects of desmopressin on hemostatic parameters in the normal dog. AB - Seven normal unanesthetized dogs were infused with desmopressin in saline (doses 0.2, 0.4 and 0.6 micrograms/kg i.v.) or saline alone, on separate occasions in order to determine the effects of desmopressin on circulating factor VIII coagulant and factor VIII-related antigen activities, on partial thromboplastin times and prothrombin times, on blood platelet count and packed cell volume, and on serum osmolarity. Desmopressin caused a rapid dose-dependent elevation in both factor VIII activities peaking at 30-60 minutes postinfusion. At a dosage of 0.6 microgram/kg desmopressin induced rises in factor VIII coagulant activity and factor VIII-related antigen of 150% and 198% of the preinfusion levels respectively, while the half disappearance times were approximately five and six hours respectively. The other parameters were not significantly affected by even the highest dose of desmopressin used. These results indicate that normal dogs respond to desmopressin in a manner similar to man. The major differences are in the dosage required to produce comparable effects (higher in dogs), and in the fact that the factor VIII-related antigen activity consistently responds to a greater degree than the coagulant activity. It is concluded that desmopressin may have particular value in stimulating elevations in plasma factor VIII-related antigen in dogs deficient in this plasma protein. Six dogs were pretreated with the endorphin inhibitor, naloxone, (0.04 mg/kg I.V.) or sterile saline, three minutes prior to infusion with desmopressin at a dose of 0.6 microgram/kg i.v.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093042 TI - Malnutrition and the heart. AB - Earlier concepts that the heart is spared in malnutrition have been shown to be incorrect. Inadequate intake of protein and energy results in proportional loss of skeletal and myocardial muscle. As myocardial mass decreases, so does the ability to generate cardiac output; however, various compensatory factors come into play. Nutritional supplementation for malnourished patients reverses the compensatory factors and may increase the short-term potential for heart failure. Severe cardiac debility results in poor nutrition, which may in turn produce unsuspected but clinically significant myocardial atrophy. Nutritional support may play a role in improving cardiac function in selected patients with cardiac cachexia who are being prepared for cardiac surgery and in patients with rapid weight loss who are at risk for sudden death due to arrhythmias. Malnutrition is common in hospitalized patients, and many patients in hospital now receive nutritional supplementation; both facts have important cardiac implications. PMID- 3093043 TI - [Evaluation and treatment of lateral ankle sprain in the emergency department: is systematic radiography necessary?]. AB - The authors describe the presentation, clinical evaluation and treatment of 151 patients (mean age 36.3 years) who presented to an outpatient clinic or the emergency department between Oct. 29, 1984, and Apr. 15, 1985, for a lateral ankle sprain. About 60% of the sprains were considered minor. Although 141 patients underwent simple radiography of the ankle on the first visit, only five fractures were identified. All the fractures were uncomplicated and were treated conservatively. No common criteria could be identified to explain why some patients with sprains of moderate severity were referred to an orthopedist while others were not. Of the 53 patients interviewed, 22 still had some limitation of physical activity 6 weeks after the sprain. The presence of malleolar soft-tissue swelling, pain in the bony structures and inability to bear weight should raise the suspicion of a fracture. If radiography had been limited to patients with these signs, no fracture would have been missed, and radiography would have been avoided in 70 cases. PMID- 3093044 TI - Selective radiographic assessment of acute ankle injuries in the emergency department: barriers to implementation. PMID- 3093046 TI - Bupropion effects in attention deficit and conduct disorders. AB - Children with Attention Deficit and/or Conduct Disorders were treated with bupropion, a new antidepressant, to determine its clinical, cognitive, and EEG effects. Seventeen male patients (age range 7 to 13.4 years; mean 10.4) participated in an open clinical trial consisting of a baseline placebo period (4 weeks), bupropion therapy (8 weeks), and post-drug placebo (2 weeks). Evaluations included clinical assessments, parents, teachers, and self-ratings; cognitive tests and blood level measurements of bupropion. Fifteen patients received a daily maximum of 150 mg, one received 100 mg and one 50 mg. Clinical global improvement with bupropion therapy was marked in 5 patients, moderate in 7, mild in 2, and none in 3. The Children's Psychiatric Rating Scale indicated improvements of hyperactivity, withdrawal, anxiety, hostility/uncooperativeness, sleep disorder, antisocial behaviour, neuroticism, depression and eating disturbance. Parents' Questionnaires indicated significant improvements of conduct disorder, anxiety, hyperactivity, muscle tension and psychosomaticism. While no single cognitive test showed significant improvement, all nine tests changed in the positive direction. Adverse effects were infrequent, transient and mild. There were no clinically significant changes of the laboratory values and vital signs. Two weeks following bupropion discontinuation, clinical global improvement was maintained in 8 patients, 7 showed relapses, while 2 remained unimproved. Analyses of computerized EEG revealed that degree of clinical improvement was indexed by baseline EEG parameters and that there were significant bupropion effects on EEG measures. Double-blind trials of bupropion are recommended in child psychiatry disorders. PMID- 3093047 TI - Immunoblastic lymphadenopathy, angioimmunoblastic lymphadenopathy, and IBL-like T cell lymphoma. A spectrum of T-cell neoplasia. AB - Thirty cases of immunologically determined and histologically diagnosed immunoblastic lymphadenopathy (IBL), angioimmunoblastic lymphadenopathy (AILD), and IBL-like T-cell lymphoma were clinicopathologically reviewed. Clinical manifestations and laboratory findings did not reveal significant differences in these three groups. IBL, AILD, and IBL-like T-cell lymphoma showed a spectrum of histologic changes, in which proliferation of pale cells was a critical diagnostic point for the histologic malignancy. Immunostaining for their subsets revealed that 3 of 21 cases showed T4+ phenotype and the remaining 19 cases showed T8+ phenotype. Three of seven immunohistochemically determined T8+ cases simultaneously expressed Leu7+ phenotype. The latter cells were consistent with large granular lymphocytes in one case, but no clinicopathological differences from the other T8+ cases were present. IBL and AILD were considered to be T-cell malignancies, which show a spectrum of histologic features from T-cell dysplasia to peripheral T-cell lymphoma (IBL-like T-cell lymphoma). Despite intensive chemotherapy, prognosis was poor in T8+ cases of which half of the patients died within 1 year. T4+ cases showed better prognosis, but a higher incidence of synchronous second primary cancers was recognized. PMID- 3093045 TI - Comparison of three methods of recalling patients for influenza vaccination. AB - Despite recommendations supporting annual influenza vaccination for people aged 65 years or older, vaccination rates remain low. Several studies have evaluated the effect of sending mailed reminders, but few have compared alternative ways of reminding patients to receive the vaccine. In a randomized trial of 939 patients aged 65 years or older in four family practices carried out between Oct. 23 and Dec. 31, 1984, we compared three ways of reminding elderly patients to receive the vaccine: personal reminder by the physician, telephone reminder by the nurse and reminder by letter. The vaccination rates for the three groups were 22.9%, 37% and 35.1% respectively. No reminder was issued to a control group, and the rate was 9.8%. Some patients could not be reached by telephone, and some did not see the physician during the specified time. Among the patients whom the nurse actually contacted, the vaccination rate was 43.5%; the rate for patients whom the doctor actually saw was 45.1%. Overall, a telephone reminder by the nurse was the most effective method, and at an hourly salary of $16 or less this method would also be the most cost-effective. The reminders used in this study were automatically generated from a computerized medical record system. The study shows how a computerized system can be used to identify patients for whom preventive procedures are due. PMID- 3093048 TI - Some practical and theoretic concepts in the nutritional assessment of the cancer patient. AB - Two patterns of response, that due to starvation or semistarvation and that due the stress, determine whether protein-calorie malnutrition of the adult marasmus variety or hypoalbuminemic malnutrition will occur in any particular nonmalignant disease. The latter condition can have two major components, the neuroendocrine response to injury, which is in large measure mediated by hormones of the hypothalamus and adrenal gland, and the panoply of responses to interleukin-1 production and release by macrophages and monocytes upon activation, usually by phagocytosis. In some cancer patients with weight loss there are many similarities to an interleukin-1 response including increases in resting energy expenditure, whole-body protein flux and synthesis and glucose flux and recycling, hypoalbuminemia and increased albumin catabolic rates, and an adaptive low T3 state that suggest a similar injury/infection response. Separation of cancer patients with malnutrition into those with an injury/infection response and those with simple starvation may explain the heterogeneous response to nutritional support among malnourished cancer patients and suggest new feeding regimens that may uniquely benefit the stress form of cancer malnutrition. PMID- 3093049 TI - Pathophysiology of malnutrition in the adult cancer patient. AB - A number of common metastatic cancers are associated with marked weight loss at the time of diagnosis. Cancer patients with weight loss at the time of diagnosis have decreased mean survival compared to similar cancer patients without weight loss. Provision of excess calories alone does not appear to change median survival in patients with advanced cancer and many patients either maintain body weight or lose weight while receiving calories which would be predicted to result in weight gain. The authors recently have extended their studies to head and neck cancer patients without detectable metastatic disease in order to detect systemic metabolic effects of a localized tumor. These patients failed to gain weight despite the administration of apparently adequate calories by continuous enteral alimentation. Abnormalities of carbohydrate metabolism with secondary effects on fat and protein metabolism have been identified in several populations of patients with common cancers. These abnormalities offer potential points of intervention which may enhance nutritional therapy as rehabilitation and as a potential biological modifier of the response of specific cancers to chemotherapy, radiation therapy, or surgery. PMID- 3093050 TI - The pathophysiology of undernutrition in the child with cancer. AB - The physiologic consequences of malnutrition in children with cancer are reviewed. It is stressed that the child with cancer has a nutritional state that is no different from the average population from which the child comes. What little malnutrition is seen is calorie malnutrition. The physiologic consequences are those seen in any malnourished patient. Once the patient is being treated for cancer and the cancer course has progressed, the complications of chemotherapy and radiotherapy add to the difficulty in interpretation. However, the problem of decreased resistance to infection is one of the major problems that result from this malnutrition. The one nutrient found deficient in children with cancer is iron. Because transferrin is sensitive to prolonged protein malnutrition and because of the high level of ferritin in children with certain cancers, interpretation of laboratory values defining iron deficiency is difficult and iron homeostasis may well be very deranged. PMID- 3093051 TI - The value of parenteral nutrition support. Chemotherapy and radiation treatment. AB - Nutritional support in chemotherapy and radiation therapy patients is a very attractive concept. This group of patients frequently begins treatment malnourished, and the malnutrition becomes worse because of treatment-related nausea and vomiting, mucositis, fever and other side effects. Effective nutritional support would enhance wound healing and visceral function, improve cellular immunity and allow delivery of adequate drug and irradiation doses, thereby increasing response rates and prolonging survival. Unfortunately, standard techniques of parenteral nutritional support have had only limited success in advanced cancer patients. Weight gain is possible and immune function may be improved, but definite benefit in response rates and survival with chemotherapy and radiation remains to be proven. Currently the author believes that the following are acceptable indications for parenteral nutrition in chemotherapy and radiation patients: patients who cannot eat or digest properly because of tumor obstruction, surgical resection of gut, or other complications who have a reasonable life expectancy; cachectic patients with responsive neoplasms who could not tolerate aggressive treatment without short-term nutritional support; and patients suitable for trials of nutritionally modified solution or alterations in standard techniques. Future studies might consider longer periods of support, increased concentrations of nutrients or, conversely, decreased amounts of nutrients needed by the tumor, if such needs could be identified. PMID- 3093052 TI - The value of nutrition support in children with cancer. AB - A positive stance towards nutrition support of the child with cancer assures potential for normal growth, development, and quality of life during extended oncologic treatment. Data from recent studies of children with cancer (advanced neuroblastoma, Wilms' tumor) demonstrate the importance of integrating nutrition staging, assessment, and support into treatment protocols. Patients with solid tumors and lymphomas who are malnourished at diagnosis have a poor outcome when compared to nourished counterparts. Enteral nutrition (intensive nutrition counseling and favorite, nutritious foods) is effective in low nutritional risk groups but ineffective in preventing or reversing protein-energy malnutrition in high nutritional risk groups. For high-risk groups, central parenteral nutrition is a relatively short-term, but important, support measure which allows children to grow despite extended periods of intense oncologic treatment. The patient's nutritional course may affect bone marrow suppression and the ability to tolerate aggressive chemotherapeutic treatment. Although treatment tolerance may be improved with nutrition support, adequacy of primary oncologic treatment outweighs other supportive factors as a determinant of ultimate survival. PMID- 3093053 TI - Nutritional support in the cancer-bearing host. Effects on host and tumor. AB - Cancer patients have the highest prevalence of malnutrition of any group of hospitalized patients. The potential causes of this malnutrition are numerous, as elements of both starvation and stress are evident in the cancer-bearing host. The presence of the tumor alone may lead to reduced intake of nutrients and treatment modalities of surgery, chemotherapy, and radiation therapy further exacerbate nutritional deficits. It is clear that the tumor requires energy substrates to grow, and that these substrates are exacted from the host. Animal studies identify progressive nutritional depletion concomitant with increasing tumor growth during ingestion of a regular diet. This appears predominantly due to reduced dietary intake in addition to host metabolic alterations. In animal/tumor models deliberate dietary protein depletion results in severe host weight loss, but also causes diminished tumor growth rates. Dietary manipulation in these animal/tumor models have demonstrated methods of improving tumor response to chemotherapy by manipulation of tumor growth rates. In addition, drug pharmacokinetics have been altered by dietary manipulation. However, data from animal/tumor models are not directly applicable to man since the tumor in animals usually results in the death of the host within six to eight weeks. Nevertheless, controlled laboratory studies in animals provide basic metabolic information which promotes understanding of host/tumor relationships in man. In cancer patients malnutrition has prognostic value, leads to a distortion of body composition with erosion of body protein and fat stores, and compromises the delivery of adequate therapy. There is no direct objective evidence of accelerated tumor growth in humans with cancer who receive nutritional support as part of their treatment regimen. The host benefits to the extent that body composition is at least maintained during the period of nutritional repletion. Thus, nutritional support provides support to the patient during periods of treatment and dietary deprivation. No improvement in the tumor's response to therapy, however, has been demonstrated by this approach. PMID- 3093054 TI - Gastrointestinal toxicity of chemotherapy and the influence of hyperalimentation. AB - The effect of combination chemotherapy on human small intestinal morphology and disaccharidase activities and their relation with clinical and chemical (fecal wet weight and K-excretion) parameters for gastrointestinal toxicity were evaluated in patients with disseminated malignant melanoma receiving enteral normoalimentation (NA). Also evaluated were the supposed protective effects on gastrointestinal toxicity of enteral hyperalimentation (HA) with an elemental diet. After chemotherapy, a comparable decrease in villus height, total mucosal height, and mitotic index was found in jejunal biopsy specimens of both groups. However, in the NA group, the crypt depth decreased (in contrast to the HA group), whereas the disaccharidase activities in the HA group deteriorated to lower values than in the NA group. The authors found no correlation between disaccharidase levels and mucosal morphology, nor was there a correlation between these variables, fecal parameters and clinical diarrhea, suggesting that diarrhea occurring after chemotherapy was not due to loss of mucosal tissue or decrease in enzyme activities. A protective effect of HA with an elemental diet on gastrointestinal toxicity could not be established. PMID- 3093055 TI - Richter's syndrome with two different B-cell clones. AB - The diagnoses of chronic lymphocytic leukemia (CLL) in prolymphocytic transformation, and diffuse large cell lymphoma (DLC), were made simultaneously in a 71-year-old man. The DLC showed mu lambda surface immunoglobulin. The CLL in a lymph node and in the peripheral blood showed mu kappa. Immunoglobulin gene DNA analysis confirmed the presence of different rearrangements in the heavy and light chain genes of the CLL and DLC. Other cases reported of Richter's syndrome are discussed, and it is concluded that there may be two types of Richter's syndrome, those arising from transformation of a single clone, and those occurring from expansion of two morphologically and immunologically distinct clones, as, it is believed, is the case in this patient. PMID- 3093056 TI - Mantle zone lymphoma with central nervous system involvement. AB - A 68-year-old man with a 7-year history of lymphocytosis and lymphadenopathy is described. Accelerated disease, indicated by bilateral optic nerve and cerebrospinal fluid involvement, prompted thorough histologic and immunologic assessment. Although initially believed to have chronic lymphocytic leukemia (CLL), results showed mantle zone lymphoma (MZL) with central nervous system (CNS) involvement. The authors believe that this represents the first case of MZL with CNS involvement. PMID- 3093058 TI - Interspecies comparison of polycyclic aromatic hydrocarbon metabolism in human and rat mammary epithelial cells. AB - Our laboratory has developed optimized and uniform methods for the isolation and culture of normal mammary epithelial cells from both rats and humans. We have reported that, in a cell-mediated mutagenesis assay, treatment of rat mammary epithelial cells with 7,12-dimethylbenz(a)anthracene, but not benzo(a)pyrene, resulted in significant rates of mutagenesis in cocultured V-79 cells. An opposite mutation pattern was found with human cells under identical conditions. To determine the mechanism of this species-specific difference in polycyclic aromatic hydrocarbon-induced mutagenesis patterns, we then studied the abilities of the human and rat mammary epithelial cells to metabolize benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene. Quantitative levels of carcinogen metabolism were found to be highly dependent on the cell culture densities, although this factor appeared to have little qualitative effect. The most significant qualitative difference in polycyclic aromatic hydrocarbon metabolism between the two species was the ability of the rat, but not the human, mammary epithelial cells to conjugate significant amounts of either polycyclic aromatic hydrocarbon to glucuronic acid. Other aspects of carcinogen metabolism, including production of the precursors to known active metabolites of benzo(a)pyrene and 7,12 dimethylbenz(a)anthracene, were similar though not identical. These results, which address only primary metabolism of the polycyclic aromatic hydrocarbons, do not indicate a simple metabolic explanation for the species-specific pattern found in the mammary cell-mediated mutagenesis assay. They do suggest that the effects of cell culture density must be carefully considered in order to properly analyze either interindividual or species differences in carcinogen metabolism. PMID- 3093057 TI - Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced induction of Epstein Barr virus early antigen in Raji cells by some inhibitors of tumor promotion. AB - The effects of some compounds, which have been reported to inhibit tumor promotion in vivo, on the induction of the early antigen (EA) of Epstein-Barr virus (EBV) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells were examined. The inhibitors of the cascade process involving arachidonic acid, indomethacin, nordihydroguaiaretic acid, phenidone and p-bromophenacyl bromide, effectively inhibited EBV-EA induction by TPA. Two flavonoids, morin and kaempferol also inhibited EA induction. Among antioxidants, butylated hydroxytoluene effectively inhibited EA induction, though alpha-tocopherol did not show any inhibition of EA induction at concentrations of up to 150 micrograms/ml. N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, and esculetin showed inhibitory effects on EA induction, though slight cytotoxicity was observed. L-1-p-Tosylamino-2-phenylethyl chloromethyl ketone, a protease inhibitor, showed cytotoxicity and no specific inhibition of EA induction. Five kinds of steroids, cortisone, hydrocortisone, prednisolone, dexamethasone and fluocinolone acetonide showed no inhibitory effect on EA induction at concentrations of up to 100 micrograms/ml. In addition, the relationship between the inhibition of EBV-EA induction and that of tumor promotion is discussed. PMID- 3093059 TI - Dansyl lysine, a new probe for assaying heat-induced cell killing and thermotolerance in vitro and in vivo. AB - Heat induces an increase in the fraction of cells staining with the nontoxic fluorescent membrane dye dansyl lysine (DL). The fraction of cells excluding DL can, under certain circumstances, be closely correlated to the fraction of cells surviving a heat treatment. Dansyl lysine has previously been shown to select for cholesterol-free membrane domains. We now describe the use of DL to provide rapid estimates of the kinetics of thermotolerance development and decay in vitro and in vivo. Following a 45 degree C-10-min heat shock, Chinese hamster ovary cells develop resistance to the lethal effects of a second heat treatment. This thermotolerance, as measured by both clonogenicity and resistance to DL staining, is maximal at approximately 12 h and gradually decays with a t1/2 of 2 to 3 days. DL staining also has utility in predicting the heat survival response in vivo. Radiation-induced fibrosarcomas grown in C3H mice were heated to 43 degrees C for 30 min. From 1 to 3 days later the tumors were excised and a single cell suspension was prepared. Tumor cells were then heated in vitro and assayed for survival or scored microscopically for DL staining. The two assays again yielded similar results showing maximal resistance by 19 h which decreased toward control heat sensitivity by 49 h. The evaluation of intrinsic heat sensitivity and induced thermotolerance is critical to rational treatment design in clinical hyperthermia. DL staining is rapidly quantitated by flow cytometry and can be applied to biopsy samples to provide estimates of heat sensitivity within hours. PMID- 3093060 TI - Effects of swainsonine and polyinosinic:polycytidylic acid on murine tumor cell growth and metastasis. AB - Increased sialylation and branching of asparagine-linked oligosaccharides have recently been associated with both neoplastic transformation and the metastatic phenotype. Swainsonine, an inhibitor of Golgi alpha-mannosidase II blocks the synthesis of sialylated tri- and tetraantennary asparagine-linked oligosaccharides and results in the expression of hybrid-type oligosaccharides at the cell surface. Both the lymphoid tumor line MDAY-D2 and B16F10 melanoma cells were less metastatic when grown in swainsonine (0.3 micrograms/ml) for 48 h prior to injection of the cells into the lateral tail veins of mice. The addition of swainsonine (2.5 micrograms/ml) to the drinking water of the mice further reduced the incidence of lung colonization by B16F10 melanoma cells. MDAY-D2 tumors removed from mice on swainsonine-supplemented drinking water showed a loss of leukoagglutinin-binding complex-type oligosaccharides similar to that of tumor cells cultured in medium containing swainsonine. The growth rate of s.c. MDAY-D2 tumors was not reduced by the addition of swainsonine to the drinking water of the host; however, when mice were given two i.p. injections of the interferon inducing agent polyinosinic:polycytidylic acid in addition to swainsonine, the primary tumor grew at a reduced rate compared to either treatment alone. Swainsonine alone did not inhibit tumor cell growth in vitro; however, the drug enhanced the antiproliferative effect of interferon. The survival time of mice bearing established MDAY-D2 metastases was extended by treating the animals with swainsonine and polyinosinic:polycytidylic acid; however, the number of long-term survival was unchanged. Swainsonine-treated tumor cells appeared to be compromised in two ways: reduced organ colonization potential; and drug-treated MDAY-D2 cells were more sensitive to the antiproliferative effects of interferon in vitro and in vivo. PMID- 3093061 TI - Inhibition of experimental metastasis by castanospermine in mice: blockage of two distinct stages of tumor colonization by oligosaccharide processing inhibitors. AB - The extent of maturation of the oligosaccharide subunits of tumor cell glycoproteins appears to correlate with malignant potential, suggesting that modification of oligosaccharide structures may alter metastatic capacity. Castanospermine, a recently discovered inhibitor of glucosidase I, was tested for its effect on experimental metastasis of B16-F10 murine melanoma cells and was compared to treatment with swainsonine and tunicamycin. All three drugs block different steps in the pathway of glycoprotein processing yet each was a potent inhibitor of pulmonary colonization after i.v. injection of treated cells into C57BL/6 mice (greater than or equal to 80% inhibition). This result indicates a generality of inhibition of experimental metastasis by blockage of protein glycosylation or oligosaccharide processing and strongly implicates carbohydrate residues in at least one critical step of the metastatic cascade. Cytotoxic side effects could not account for the inhibitory activity. In order to identify a possible mechanism of inhibition of colonization, the adhesive behavior and pulmonary retention properties of B16-F10 cells treated with the above inhibitors were examined. Tunicamycin-treated B16-F10 cells exhibited poor adhesion to substrate-adsorbed fibronectin and laminin, whereas both castanospermine- and swainsonine-treated cells possessed near normal adhesive capacity; furthermore, the initial rate of loss of tunicamycin-treated cells from the lungs of mice was substantially greater than either control, castanospermine- or swainsonine treated cells. These data suggest that these processing inhibitors can block experimental metastasis by at least two different mechanisms. The antimetastatic effect of tunicamycin may be related to interference in tumor cell-extracellular matrix interactions, whereas treatment with castanospermine or swainsonine appears to block at a stage distal to initial tumor cell arrest. PMID- 3093063 TI - Activation or suppression of the tumoricidal properties of monocytes from cancer patients following treatment with human recombinant gamma-interferon. AB - The purpose of these studies was to examine the antitumor properties of blood monocytes from patients undergoing phase I trials with recombinant human gamma interferon (rIFN-gamma). Thirty-one patients with different malignancies were divided into three major treatment groups. The first group of patients received rIFN-gamma by a 6-h i.v. infusion. Activation of blood monocytes was dependent upon the dose of rIFN-gamma administered. The second group of patients received IFN-gamma by a continuous 24-h i.v. infusion. In general, this treatment did not produce antitumor activity in blood monocytes. The third group of patients received daily i.m. injections of rIFN-gamma. Daily i.m. administrations of 0.25 0.5 mg rIFN-gamma/m2/day produced significant activation of antitumor properties in the patients' monocytes, whereas the daily i.m. administrations of 1 mg IFN gamma/m2/day did not. In fact, the blood monocytes from these patients did not even respond to optimal activating stimuli in vitro. We conclude that the systemic administration of appropriate amounts of IFN-gamma can activate blood monocytes of cancer patients to become tumor cytotoxic. High doses of the same biological should be avoided since it can actually suppress the desired effect. For biologicals with immunostimulatory activity the concept that "more drug is better" may not be operative. PMID- 3093062 TI - Anticarcinogenic and hepatotoxic interactions between retinyl acetate and butylated hydroxytoluene in rats. AB - The natural retinoid, retinyl acetate (RA), and the phenolic antioxidant, butylated hydroxytoluene (BHT), are both effective inhibitors of mammary carcinogenesis in rats. The present study was designed to determine if an increased inhibition of mammary carcinogenesis is obtained when RA and BHT are administered in combination. At age 50 days (time 0), virgin, female Sprague Dawley rats received a single intragastric instillation of 16 mg of 7,12 dimethylbenz(a)anthracene dissolved in 1 ml sesame oil. Groups of 30 carcinogen treated rats received Wayne Lab Chow supplemented with (per kg diet) 250 mg RA, 5000 mg BHT, or 250 mg RA plus 5000 mg BHT by the following schedule: -2 to +1 week; +1 week until the end of the experiment; -2 weeks to end; or none. Combined administration of RA plus BHT by the -2 weeks to end schedule was more effective in mammary cancer chemoprevention than was RA alone or BHT alone; the interaction of RA and BHT was additive. Similarly, administration of RA plus BHT by the -2 weeks to end protocol was more active in chemoprevention than was RA plus BHT administered either from weeks -2 to +1 or +1 week to end. Chronic exposure to RA plus BHT induced a high incidence of hepatic fibrosis and bile duct hyperplasia; these changes were not observed in controls and were seen in low incidence in animals exposed to RA only or BHT only. These data indicate that enhanced anticarcinogenic activity can be obtained through the use of "combination chemoprevention" regimens; however, chemopreventive compounds may interact not only to inhibit carcinogenesis but also to induce toxicity. PMID- 3093064 TI - Methylthioadenosine phosphorylase deficiency in human leukemias and solid tumors. AB - 5'-Methylthioadenosine (MTA) is a naturally occurring nucleoside which is degraded by MTA phosphorylase (MTAase) to adenine and methylthioribose-1 phosphate in all normal mammalian cells. These products of the phosphorylytic cleavage of MTA are recycled to the nucleotide pool and methionine, respectively. Thus, supplemental MTA could theoretically be utilized by MTAase-containing cells as a source of methionine and adenine. In fact, in vitro experiments have shown that MTAase-containing cells proliferate normally in methionine-free medium if MTA is added to the cultures (M. K. Riscoe and A. J. Ferro, J. Biol. Chem., 259: 5465-5471, 1984). In contrast, MTAase-deficient malignant cell lines do not proliferate under these conditions. In light of these observations and the recent demonstration (N. Kamatani et al., Blood, 60: 1387-1391, 1982) that a proportion of acute lymphoblastic leukemias lack MTAase, we wished to determine if this enzyme deficiency occurs in a variety of human neoplasms. Accordingly, malignant cells from eight patients with acute nonlymphocytic leukemia and ten patients with various solid tumors were assayed for MTAase activity. Samples from one of the eight acute nonlymphocytic leukemia patients and three of the 10 solid tumor patients (one with melanoma, one with squamous cell lung cancer, and one with adenocarcinoma of the rectum) had undetectable MTAase activity. In contrast, erythrocytes, neutrophils, and monocytes isolated from normal subjects and from patients with immunodeficiency syndromes or cancer all contained enzyme activity. In addition, the methods of preservation, storage, and cell disruption did not affect MTAase activity. These observations confirm and extend the findings of Kamatani et al. (Blood, 60: 1387-1391, 1982) by demonstrating that MTAase deficiency occurs in a variety of human malignancies including acute nonlymphocytic leukemia and solid tumors. This metabolic difference between normal and malignant cells may be therapeutically exploitable. PMID- 3093065 TI - Cellular distribution of a B-cell specific surface antigen (gp54) detected by a monoclonal antibody (anti-BL4). AB - A monoclonal antibody (anti-BL4) recognizing a previously characterized Mr 54,000 glycoprotein (gp54) was developed by immunizing BALB/c mice with cells from a precursor B-cell line (Josh-7). In normal individuals, this antigenic molecule was present on tonsillar B-cells (60-80%) and on a fraction of peripheral blood B cells (5-25%). BL4 (gp54) expression was investigated in 186 patients with a variety of hematological malignancies using indirect immunofluorescence and flow cytometric analysis. Twenty-six of 37 cases of B-cell chronic lymphocytic leukemia (CLL) and 18 of 33 cases of B-cell non-Hodgkin's lymphoma were BL4 positive. Surface expression of BL4 on reactive cases of CLL and non-Hodgkin's lymphoma was brighter than those of B1, B2, and B4, BL4 positive CLL cases expressed a higher proportion of mouse rosette forming cells and Leu-1 positive cells than the BL4 negative subgroup and were not associated with elevated serum immunoglobulin levels. Four of 7 BL4 negative CLL cases were associated with increased serum levels of immunoglobulin M. Lymphoblasts from 14 of 14 cases of non-T acute lymphoblastic leukemia and 3 of 3 pre-B lymphoid blast crisis of chronic myeloid leukemia were BL4 negative. Neoplastic cells from 2 of 3 cases of Waldenstrom's macroglobulinemia and 4 of 7 cases of hairy cell leukemia were BL4 reactive. None of 7 cases of multiple myeloma and plasma cell leukemia were BL4 positive. All 11 T acute lymphoblastic leukemia cases, 6 other T-cell malignancies, 5 cases of Hodgkin's disease, 51 cases of acute nonlymphocytic leukemia, and 9 cases of chronic myeloid leukemia in chronic phase thus far studied were BL4 negative. An in vitro induction experiment using phorbol ester on a case of B-CLL demonstrated disappearance of BL4 accompanied with further B cell differentiation. Our study further substantiates the previous finding that gp54 is a differentiation antigen restricted to the B-cell lineage and expressed during the intermediate stage of B-cell ontogeny. PMID- 3093066 TI - Effect of polyamine depletion in vivo by DL-alpha-difluoromethylornithine on functionally distinct populations of tumoricidal effector cells in normal and tumor-bearing mice. AB - The objective of the present investigation was to examine the effect of in vivo polyamine depletion by DL-alpha-difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, on cell-mediated tumoricidal activity in normal and tumor-bearing (B16 melanoma) mice. DFMO treatment in vivo for 6 days reduced splenic leukocyte polyamine levels and the induction of cytotoxic T-lymphocytes (greater than 50%) in both normal and tumor-bearing mice. However, substantially less inhibition was observed in the ability to generate cytotoxic T-lymphocytes following 18 days of DFMO treatment. In contrast, DFMO treatment for 6 or 18 days did not impair splenic natural cell-mediated cytotoxicity, assessed against natural killer sensitive YAC-1 target cells and natural cytotoxic sensitive WEHI-164 target cells, in normal or tumor-bearing mice. Natural cell-mediated cytotoxicity was not observed against fresh B16 melanoma cells. However, macrophage-mediated tumoricidal activity directed against B16 melanoma cells was augmented 79% following 6 but not 18 days of DFMO treatment. These results demonstrate that DFMO can exert very selective effects on functionally distinct populations of antitumor effector cells in vivo depending upon the schedule of DFMO administration. PMID- 3093067 TI - Enrichment of antitumor effector cells that are effective in vivo from spleen cells of tumor-bearing mice through the use of Dolichos biflorus lectin. AB - Spleen cells of X5563 tumor-bearing mice were fractionated with Dolichos biflorus lectin (DBA) into DBA+ (agglutinable with DBA) and DBA- (nonagglutinable with DBA) fractions. The DBA- cells showed antitumor activity specific for X5563 cells in vivo when injected into mice together with X5563 cells (Winn assay) or injected i.p. into mice previously inoculated s.c. with X5563 cells (adoptive transfer) with simultaneous administration of interleukin-2. Both DBA+ and DBA- cells have the cell surface phenotype of Lyt-1-2+, but only DBA- cells exhibit antitumor activity in vivo, while DBA+ cells have stronger cytolytic activity against X5563 cells in vitro than DBA- cells. This cell separation method involving the use of DBA is simple and gives reproducible results and high yields of viable cells. PMID- 3093068 TI - Eicosanoid synthesis by cultured human urothelial cells: potential role in bladder cancer. AB - Prostaglandin (PG) H synthase and eicosanoid products of arachidonic acid metabolism have been implicated in several steps in the carcinogenic process. This study assessed these parameters using primary cultures of human urothelial cells. To determine the possible presence of permeability barriers to agonist stimulation, incubations were performed with adherent cells in the presence or absence of thioglycolate pretreatment or with cell suspensions. No evidence for permeability barriers was observed. With adherent cells in the absence of thioglycolate, radioimmunoassayable PGE2 was stimulated by epinephrine less than 12-O-tetradecanoylphorbol-13-acetate = thrombin less than bradykinin = A23187 much less than arachidonic acid. Tumor promoters but not non-tumor promoters stimulated PGE2 synthesis. 1-Oleoyl-2-acetylglycerol which like 12-O tetradecanoylphorbol-13-acetate activates protein kinase C also increased PGE2 synthesis. Cells prelabeled with [14C]arachidonic acid were exposed to agonists and the profile of eicosanoids synthesized was assessed by high performance liquid chromatography. With bradykinin, the pattern of eicosanoids synthesized was 6-keto-PGE1 alpha (12% of total 14C label), thromboxane B2 (0.4%), PGF2 alpha (1.7%), PGE2 (18%), PGD2 (1%), leukotrienes (0.4 to 1%), 12-hydroxy-5,8,10 heptadecatrienoic acid (3%), 15-hydroxy-5,8,11,13-eicosatetraenoic acid (4%), 12 hydroxy-5,8,10,14-eicosatetraenoic acid (0%) and 5-hydroxy-5,8,12,14 eicosatetraenoic acid (2%). Thus, human urothelial cells contain both prostaglandin H synthase and lipoxygenase pathways with the former being more prominent. These pathways may participate in urinary bladder carcinogenesis. PMID- 3093069 TI - Relationship between circulating plasminogen activators and tumor development in mice. AB - Plasminogen activators (PAs) present in the plasma of BALB/c mice and produced in vitro by murine tumor cell cultures (B77-3T3, SR-BALB, AA6) have been characterized using electrophoretic-zymographic techniques. BALB/c mouse plasma contains a main PA activity with an approximate molecular weight of 88,000 and pI 6.3, inhibited by anti-human tissue-type plasminogen activator (t-PA) serum, here defined as murine t-PA. On the contrary, all tumor cells tested release a PA activity with a molecular weight of 44,500 and pI 9.2 characteristic of urokinase type activator (murine u-PA). The injection s.c. of the different tumorigenic cells into BALB/c mice leads to tumor development and to a rapid increase of t-PA from the first day following the injection. This early enhancement of t-PA activity is not detectable in mice given injections of lethally irradiated B77 3T3 cells. Moreover the development of the tumor in the animals is related to the appearance of increasing levels of u-PA in the blood. This activity is detectable in the plasma of treated mice almost 2 wk before detection of a tumor 1 mm in diameter. During tumor development, the molecular weight of the u-PA and t-PA forms present in the plasma does not change, while there is a decrease of the isoelectric point of the u-PA leading to the appearance of distinct PA activities with pI 7.6 and 8.9. Syngenic and allogenic lymphocytes, injected in BALB/c mice, do not induce any modification in the pattern of the plasma PA. The injection of highly metastatic cells, as opposed to nonmetastatic or low-metastatic cells, does not give rise to detectable levels of u-PA in the plasma of treated mice. These data suggest that the lack of plasma u-PA activity facilitates the formation of metastates, while the increase of this activity is important in tumor development and is independent of the metastatic potential of the injected cells. PMID- 3093070 TI - 1,25-Dihydroxyvitamin D3-regulated expression of genes involved in human T lymphocyte proliferation and differentiation. AB - 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited the secretion of gamma interferon from human T-lymphocytes activated by the calcium ionophore, A23187, or phytohemagglutinin with or without 12-O-tetradecanoylphorbol-13-acetate. The agent also inhibited cell proliferation and interleukin 2 secretion by these cells. The inhibition of gamma-interferon secretion was time and dose dependent and partially abolished by the addition of exogenous human recombinant interleukin 2. To elucidate the molecular events by which 1,25-(OH)2D3 inhibits cell proliferation and lymphokine secretion, complementary DNA probes were used to follow the expression of genes involved in human T-lymphocyte proliferation and differentiation. 1,25-(OH)2D3 inhibited the expression of interleukin 2 and gamma-interferon messenger RNA in human lymphocytes activated by phytohemagglutinin and 12-O-tetradecanoylphorbol-13-acetate. It also inhibited the accumulation of c-myc protooncogene messenger RNA and, to a lesser extent, interleukin 2 receptor messenger RNA in these cells. However, it did not affect the expression of the HLA-DR gene. These results suggest that 1,25-(OH)2D3 selectively regulates T-lymphocyte activation-related genes at the level of messenger RNA. PMID- 3093071 TI - Effects of 12-O-tetradecanoylphorbol-13-acetate on carcinogen-induced mouse mammary lesions in organ culture. AB - Mammary glands of young female BALB/c mice develop hyperplastic nodule-like alveolar lesions (NLAL) in response to a 24-h exposure to 7,12 dimethylbenz(a)anthracene (DMBA; 2 micrograms/ml) on Day 3 during a 24-day organ culture. Experiments were conducted to determine if 12-O-tetradecanoylphorbol-13 acetate (TPA), a known tumor promoter, can influence the development of DMBA induced NLAL in mammary gland organ culture. Mammary glands were incubated with TPA (25 ng/ml) for various periods of time in the presence of appropriate hormone combinations. Results indicated that the presence of TPA in the medium between Days 9 to 14 of the culture period enhanced both the incidence and multiplicity of DMBA-induced NLAL; however, it was ineffective when included in the medium between Days 4 to 9 or 19 to 24 of the organ culture. Toxicity of TPA was evident when it was present during the entire culture period subsequent to DMBA treatment. Computer-assisted image analysis of NLAL in the glands determined the area covered by these lesions within the gland. It was observed that 7.8% of the area was covered by NLAL in DMBA plus TPA-treated glands as compared to 2.5% by DMBA treatment alone. These results provide a model for initiation-promotion studies of mammary carcinogenesis in vitro, as well as a modified approach for quantitative analysis of structural alterations. PMID- 3093072 TI - Role of cytoskeleton changes and expression of the H-ras oncogene during promotion of neoplastic transformation in mouse epidermal JB6 cells. AB - The relationship between cytoskeletal changes and oncogene expression in initiated cells during exposure to a tumor promoter was investigated in the phorbol ester-sensitive murine epidermis-derived cell line JB6 (P+ cells) and its promotion-insensitive variant (P- cells) using immunocytochemical methods, soft agar assays, and tumorigenicity tests in nude mice. Cytoskeletal changes in P+ and P- cells induced by short-term incubation with 12-O-tetradecanoylphorbol-13 acetate (TPA) were similar. Prolonged incubation with TPA allowed P- cells to regain their original appearance and resulted in growth inhibition; however, the extended presence of TPA produced in P+ cells persistent alterations in the distribution of actin, vinculin, and fibronectin. P+ cells proceeded to develop multilayered foci. Using monoclonal antibodies, we detected the H-ras oncogene encoded Mr 21,000 protein (p21) exclusively in focus-forming cells. Both the observed morphological changes and the expression of p21 were reversible in P+ cells when TPA exposure was terminated soon after foci had developed. In order for TPA-treated P+ cells to grow as tumors in nude mice, multiple cycles of exposure to TPA in conjunction with clonal expansion in agar were necessary. The results indicate that there exists during promotion of the P+ JB6 cells a relationship between expression of the H-ras gene product p21 and enhanced proliferation with focus formation and that both expression of p21 and focus formation depend on the continuous presence of the promoting agent. PMID- 3093073 TI - Serum galactosyltransferase as a prognostic marker in patients with solid tumors. AB - The serum level of galactosyltransferase was measured in a group of 218 patients with a variety of solid tumors and most with advanced disease. The pretreatment enzyme level showed little potential as a diagnostic tumor marker, and its change with treatment did not reflect the initial response. There was, however, a significant correlation between the length of survival and the pretreatment enzyme level. Patients with normal levels survived over twice as long as those with elevated levels. When Cox's proportional hazards regression analysis was used to compare the prognostic potential of galactosyltransferase with a number of known clinical indicators of prognosis, the variable most related to survival was performance status (P less than 10(-4) followed by galactosyltransferase (P = 0.01) and then the extent of disease (P = 0.03). The other variables, such as previous therapy, the type, site, and size of primary tumor, did not contribute significantly to the relationship with survival. The pretreatment level of galactosyltransferase is therefore a relatively independent prognosticator of survival and, as such, could be potentially useful in patient management by increasing the accuracy of the initial assessment of prognosis. PMID- 3093074 TI - Diagnosis of mucopolysaccharidoses using 1H-n.m.r. spectroscopy of glycosaminoglycans. PMID- 3093075 TI - Structure of the serine-containing capsular polysaccharide K40 antigen from Escherichia coli O8:K40:H9. AB - The structure of the K40 antigenic capsular polysaccharide (K40 antigen) of E. coli O8:K40:H9 was elucidated by determination of the composition, 1H- and 13C n.m.r. spectroscopy, periodate oxidation and Smith degradation, and methylation analysis. The K40 polysaccharide consists of [(O-beta-D-glucopyranosyluronic acid)-(1----4)-O-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-(1----6)-O -(2 acetamido-2-deoxy-alpha-D-glucopyranosyl)-(1----4)] repeating units. All of the glucuronic acid residues are substituted amidically with L-serine. PMID- 3093077 TI - [Sepsis--problems of meeting energy needs]. PMID- 3093076 TI - Structure identification of the complex-type, asparagine-linked sugar chains of beta-D-galactosyl-transferase purified from human milk. AB - The asparagine-linked sugar chains of human milk galactosyltransferase were quantitatively released as oligosaccharides from the polypeptide backbone by hydrazinolysis. They were converted into radioactive oligosaccharides by sodium borotritiate reduction after N-acetylation, and fractionated by paper electrophoresis and by Bio-Gel P-4 column chromatography after sialidase treatment. Structural studies of each oligosaccharides by sequential exoglycosidase digestion and methylation analysis indicated that the galactosyltransferase contains bi, tri-, and probably tetra-antennary, complex type oligosaccharides having alpha-D-Manp-(1----3)-[alpha-D-Manp-(1----6)]-beta-D Manp -(1----4)-beta-D- GlcpNac-(1----4)-alpha-L-[Fucp-(1----6)]-D-GlcNAc as their common core. Variation is produced by the different locations and numbers of the five different outer chains: beta-D-Galp-(1----4)-D-GlcNAc, alpha-L-Fucp-(1----3) [beta-D-Galp-(1----4)]-D-GlcNAc, alpha-NeuAc-(2----6)-beta-D-Galp-(1----4)-D GlcNAc, alpha-L-Fucp-(1----3)-[beta-D-Galp-(1----4)]-beta-D-GlcpNAc-(1---- 3) beta- D-Galp-(1----4)-[alpha-L-Fucp-(1----3)]-D-GlcNAc, and alpha-NeuAc-(2----6) beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----3)-beta-D - Galp-(1----4)-[alpha-L-Fucp (1----3)]-beta-D-GlcNAc. PMID- 3093078 TI - Carbonic anhydrase activity in primary sensory neurons. I. Requirements for the cytochemical localization in the dorsal root ganglion of chicken and mouse by light and electron microscopy. AB - Subpopulations of primary sensory neurons in mammalian dorsal root ganglion (DRG) exhibit carbonic anhydrase (CA) activity. To identify these subpopulations in DRG cells of mouse and chicken, the reliability of the cytochemical localization of the enzyme requires that several conditions be fulfilled: Preservation of the enzyme activity in glutaraldehyde-containing fixative; accessibility of the cytoenzymatic reaction throughout 20-micron thick Vibratome sections; retention of the reaction product in situ during OsO4 post-fixation; specificity of the cytoenzymatic reaction for CA activity as corroborated by the immunocytochemical detection with antibodies anti-CA II in mouse DRG; strict correlation between the CA activity and the cytological characteristics in a given subclass of neurons. On the basis of these criteria, it is concluded that the CA activity may be used as a cell marker to identify cytologically defined neuronal subpopulations and their axons in mouse DRG. In chicken DRG, CA activity is not consistently expressed in a given subclass of ganglion cells and their axons. Hence, it is assumed that the expression of CA activity by DRG cells in chicken is modulated by functional or environmental conditions. PMID- 3093079 TI - Carbonic anhydrase activity in primary sensory neurons. II. Influence of environmental factors on the phenotypic expression of the enzyme in dissociated cultures of chicken dorsal root ganglion cells. AB - Neuronal subpopulations of dorsal root ganglion (DRG) cells in the chicken exhibit carbonic anhydrase (CA) activity. To determine whether CA activity is expressed by DRG cells maintained in in vitro cultures, dissociated DRG cells from 10-day-old chick embryos were cultured on a collagen substrate. The influence exerted by environmental factors on the enzyme expression was tested under various conditions of culture. Neuron-enriched cell cultures and mixed DRG cell cultures (including numerous non-neuronal cells) were performed either in a defined medium or in a horse serum-supplemented medium. In all the tested conditions, subpopulations of cultured sensory neurons expressed CA activity in their cell bodies, while their neurites were rarely stained; in each case, the percentage of CA-positive neurons declined with the age of the cultures. The number and the persistence of neurons possessing CA activity as well as the intensity of the reaction were enhanced by addition of horse serum. In contrast, the expression of the neuronal CA activity was not affected by the presence of non-neuronal cells or by the rise of CO2 concentration. Thus, the appearance and disappearance of neuronal subpopulations expressing CA activity may be decisively influenced by factors contained in the horse serum. The loss of CA-positive neurons with time could result from a cell selection or from genetic repression. Analysis of the time curves does not support a preferential cell death of CA positive neurons but suggests that the eventual conversion of CA-positive neurons into CA-negative neurons results from a loss of the enzyme activity. These results indicate that the phenotypic expression of cultured sensory neurons is dependent on defined environmental factors. PMID- 3093080 TI - Alternative 5' exons and tissue-specific expression of the Drosophila EGF receptor homolog transcripts. AB - cDNA clones of the Drosophila epidermal growth factor receptor homolog (DER) gene were isolated and sequenced. The deduced amino acid sequence shows a similar degree of homology to the human epidermal growth factor receptor and to the rat and human neu proteins; the most striking difference is the addition of a third cysteine-rich extracellular domain in DER. The structure of the cDNA indicates the use of alternative 5' exons. Thus, the gene encodes three putative proteins differing at their N termini. The distribution of DER transcripts was analyzed by in situ hybridization. Transcripts are uniformly distributed in embryos, larval transcripts are primarily localized to proliferating tissues of the imaginal discs and brain cortex, and adult transcripts are detected mainly in the brain and ganglia. All three splicing alternatives show similar tissue distribution during development. PMID- 3093081 TI - Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. AB - A process unique to lymphocyte differentiation is the rearrangement of genes encoding antigen-specific receptors on B and T cells. A mouse mutant (C.B-17scid) with severe combined immune deficiency, i.e., that lacks functional B and T cells, shows no evidence of such gene rearrangements. However, rearrangements were detected in Abelson murine leukemia virus-transformed bone marrow cells and in spontaneous thymic lymphomas from C.B-17scid mice. Most of these rearrangements were abnormal: approximately 80% of Igh rearrangements deleted the entire Jh region, and approximately 60% of TCR beta rearrangements deleted the entire J beta 2 region. The deletions appeared to result from faulty D-to-J recombination. No such abnormal rearrangements were detected in transformed tissues from control mice. The scid mutation may adversely affect the recombinase system catalyzing the assembly of antigen receptor genes in developing B and T lymphocytes. PMID- 3093082 TI - The c-myc oncogene perturbs B lymphocyte development in E-mu-myc transgenic mice. AB - Transgenic mice bearing a c-myc oncogene subjugated to the lymphoid-specific immunoglobulin heavy chain enhancer (E mu) develop clonal B lymphoid malignancies, but most young E mu-myc mice lack malignant clones. Their prelymphomatous state has allowed us to examine how constitutive c-myc expression influences B cell development. We find that early stages are overrepresented, even before birth. Pre-B cells of polyclonal origin increase greatly, while B cells develop in reduced number. Both the pre-B and the B cells appear to be in an active state, since they are larger than normal and a greater fraction are in the cell cycle. Enforced myc expression has thus favored proliferation over maturation. Hence, a normal function of c-myc may be to regulate differentiation as well as to promote cell cycling. PMID- 3093083 TI - The localization and regulation of Antennapedia protein expression in Drosophila embryos. AB - The homeotic Antennapedia (Antp) gene of Drosophila is required for the normal differentiation of the thoracic segments during embryonic development and metamorphosis. Antibodies to a recombinant Antp protein were used to localize the protein in whole mount embryos. Antp is expressed in the nuclei of cells of the thoracic embryonic epidermis and several segments of the ventral and peripheral nervous systems. Analysis of Antp expression in mutant embryos revealed three levels of Antp regulation by genes of the bithorax complex, pleiotropic homeotic loci, and Antp itself. The distributions of the Antp and the Ultrabithorax (Ubx) proteins in doubly-labeled embryos suggest that the Ubx protein may be one direct negative regulator of Antp gene expression. PMID- 3093084 TI - Abdominal segmentation, pole cell formation, and embryonic polarity require the localized activity of oskar, a maternal gene in Drosophila. AB - Embryos derived from oskar females lack pole cells and the specialized pole plasm including polar granules. In addition, the abdominal region remains unsegmented and eventually dies. Transplantation of cytoplasm from normal embryos into mutant embryos reveals that osk-dependent activity is strictly localized at the posterior pole and has three distinct functions. In mutant embryos the activity will normalize pole cell formation when transplanted into the posterior pole and abdominal segmentation after transplantation to a more anterior, the prospective abdominal, region. Furthermore, osk activity can provoke the formation of a second "posterior center" at the anterior. The participation of the osk product in the establishment of a source of morphogenetic activity in the posterior pole plasm is discussed. PMID- 3093085 TI - Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation. AB - The chromosome of N. gonorrhoeae contains several complete expression genes coding for variant opacity proteins. DNA sequence analysis of two opacity genes derived from the same locus (opaE1) of two isogenic gonococcal variants reveals common and variable regions in these genes. Genomic blotting experiments using synthetic probes suggest gene conversion as a principle for the assembly of variant sequence information in opacity genes. The 5' region of opacity genes is composed of identical pentameric pyrimidine units (CTCTT) encoding the hydrophobic portion of the opacity leader peptide. This coding repeat is variable in a given locus with respect of the number of pentameric units. While all expression loci in a single cell are constitutively transcribed, the production of opacity proteins is determined by the coding repeat sequence on the translational level. PMID- 3093086 TI - Mechanism by which pertussis toxin breaks unresponsiveness of delayed-type hypersensitivity to sheep red blood cells in mice. AB - The mechanism by which pertussis toxin (PT) breaks the unresponsiveness of delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) was examined in B10 mice. The unresponsiveness of DTH was induced in mice by iv injection of 10(9) SRBC and broken antigen-specifically by iv injection of 500 ng of PT into mice 1 or more days after SRBC injection. The restored DTH response in the SRBC primed and PT-treated mice was accompanied by the appearance of Lyt-1-positive splenic T cells, capable of mediating DTH, fractionated in the low-density layers on a discontinuous bovine serum albumin density gradient. To examine the action of PT on the appearance of the DTH-effector cells, the splenic T cells from 10(9) SRBC-primed mice were treated with 100 ng/ml of PT for 60 min in vitro and then transferred into naive recipient mice. The PT-treated T cells acquired the ability to manifest DTH in the recipient mice several days after transfer. A large proportion of them were Lyt-1-positive small cells fractionated in the high density layers before transfer and transformed into DTH-effector cells fractionated in the low-density layers in the recipient mice after transfer. Moreover, the ability of the PT-treated cells to manifest DTH on transfer was resistant to treatment with mitomycin C. These results suggest that PT acts on the sensitized, small Lyt-1-positive T cells from the unresponsive mice to differentiate them into large T-cell blasts, capable of mediating DTH, as one of the mechanisms by which PT breaks the unresponsiveness of DTH to SRBC. PMID- 3093087 TI - The role of IL-2 and T4+ cells in the generation of human influenza virus specific CTL activity. AB - Stimulation of human peripheral blood lymphocytes (PBL) with influenza A virus leads to the generation of virus-specific cytotoxic T lymphocyte (CTL) activity as well as natural killer (NK)-like activity. In this study, we show that exogenous IL-2 augments the in vitro generation of virus-specific CTL activity, only when added some days after the initiation of the culture. Apparently, the endogenously produced IL-2 can be a limiting factor in the in vitro generation of CTL activity. The increase of influenza virus-specific CTL activity after addition of exogenous IL-2 does not affect the restriction pattern of the CTL response. So, the preferential use of certain HLA antigens as restriction elements is not due to a limiting amount of endogenously produced IL-2. Depletion of T4+ cells completely abrogates the generation of virus-specific CTL activity. Addition of exogenous IL-2 to T4+-cell-depleted cultures fully restores the generation of HLA-restricted virus-specific CTL activity. We conclude that in the in vitro generation of virus-specific CTL activity in bulk cultures of human PBL the sole function of T4+ cells in human virus-specific CTL generation is the production of IL-2, no cognitive cell interaction of T8+ CTL precursors with T4+ cells is required, and in bulk cultures T8+ cells themselves are not able to produce sufficient amounts of IL-2 to ascertain the maturation of virus-specific CTL precursors into cytolytic T cells. Finally, we show that exogenous IL-2 also has a stimulatory effect on the NK-like or lymphokine-activated killer activity, which is always concomitantly induced in virus-specific CTL generation cultures, but has no influence on the levels of IFN produced in such cultures. PMID- 3093088 TI - Phorbol-induced recruitment of lymphocytes for spontaneous cytolysis of natural killer-insensitive tumor targets. AB - Natural killer (NK) cells lyse a variety of tumor cells in vitro whereas NK depleted unsensitized lymphocytes do not have this effect. In studies designed to elucidate the NK phenomenon, a series of experiments was carried out to identify properties of NK-sensitive targets and compare these with those of NK-insensitive targets and with targets rendered sensitive by treatment with phorbol esters. Following brief exposure to phorbol-12-myristate-13-acetate (PMA), the targets were thoroughly washed, and then incubated with lymphocyte preparations which were either enriched for or depleted of NK cells. PMA treatment increased the susceptibility of sensitive targets to NK-enriched fractions by only 20-30%, but made the NK-cell-insensitive targets markedly vulnerable to these effectors (80% lysis). Unexpectedly, brief PMA exposure also rendered cells susceptible to lysis by NK-cell-depleted lymphocytes. Yet, such targets were not killed by monocytes or B lymphocytes. Elimination of T8 lymphocytes from the NK-depleted fractions abolished lysis. To explore whether PMA had induced membrane changes not detectable on electron microscopy of thin sections, freeze-fracture studies were carried out on target cells before and after treatment with PMA. Freeze-fracture replicas of target cells which had been exposed to PMA exhibited a 50% reduction of the intramembranous particles (IMP) on the external leaflet of the plasma membrane but no changes in the number or size of the IMP associated with the protoplasmic leaflet face. The exact relationship of the structural changes and enhanced susceptibility to cytolysis has not yet been established. However, the observation that normal and tumor cells can be rendered vulnerable to lysis by lymphocytes which have not been sensitized immunologically may have practical applications. PMID- 3093089 TI - Suppression of fibroblast proliferation by activated macrophages: involvement of H2O2 and a non-prostaglandin E product of the cyclooxygenase pathway. AB - Macrophages are considered promoters of fibroblast proliferation; however, suppression by activated macrophages may outweigh this effect. Activated murine peritoneal macrophages obtained by in vivo exposure to C. parvum or by in vitro LPS-activation of thioglycollate-induced macrophages, were tested for their effect on normal syngeneic dermal fibroblasts. C. parvum-activated macrophages, but not resident peritoneal macrophages suppressed fibroblast proliferation. Similarly, macrophages activated in vitro by LPS, but not those unexposed to LPS, suppressed fibroblast proliferation. Catalase partially protected fibroblasts from suppression by either activated macrophage population, suggesting involvement of H2O2 in the suppression. The effect of cyclooxygenase inhibitors on the suppression was also tested. Indomethacin, acetylsalicyclic acid, or eicosatetraynoic acid, all partially protected the fibroblasts from macrophage mediated suppression. Prostaglandins E2, E1, and F2 alpha, added exogenously at concentrations as high as 10(-6) M, failed to suppress the proliferation of the fibroblasts. These findings suggest that a non-prostaglandin product of the cyclooxygenase pathway is involved in macrophage-mediated suppression of fibroblast proliferation. PMID- 3093090 TI - Expression of class II antigens by subsets of activated T cells. AB - Gene products coded for within the HLA complex play an important role in the control of immune responses. Class I antigens, coded for by the HLA-A, B, and C loci, are expressed by virtually all mononuclear blood cells. Class II antigens, coded for by the DR, DQ, and DP loci, have a more limited tissue distribution. They are expressed by B cells, monocytes, and by activated, but not by resting, T cells. The class II molecules of B cells and antigen-presenting cells have long been of interest to immunologists, since they are involved in the presentation of antigen, in communication between T cells and B cells and between T cells and adherent cells, and in susceptibility to certain diseases. The class II antigens expressed by activated T cells, however, remain largely uncharacterized in terms of their specificity, functional significance, and molecular nature. We have studied the expression of DR and DQ antigens by activated T cells and then examined the expression of DR versus DQ antigens by Leu 2a and Leu 3a subsets of mitogen-activated populations. Our results demonstrated that, as for class II positive macrophages, the intensity of staining with monoclonal antibodies directed against DR antigens was much greater than that obtained with those directed against DQ antigens. Interestingly, the percentages of Leu 2a- and Leu 3a-positive cells which expressed DR antigens were quite similar, as were the percentages of Leu 2a and Leu 3a cells which expressed DQ. Thus, there does not seem to be preferential expression of DR versus DQ antigens by mitogen-activated T-cell subsets. Finally, though both DR-positive-DQ-positive and DR-positive-DQ negative populations were detected, few or no DR-negative-DQ-positive cells were observed in these populations. PMID- 3093091 TI - Progenitor cells in the thymus: most thymus-homing progenitor cells in the adult mouse thymus bear Pgp-1 glycoprotein but not interleukin-2 receptor on their cell surface. AB - Pgp-1-positive and interleukin-2-receptor (IL-2R)-positive cells are both minor (less than 5%) subpopulations within the adult thymus. A thymocyte population enriched for these two cell types, obtained by killing the bulk of thymocytes with anti-Thy-1 antibody and complement, contains thymus-homing progenitor cells which can transiently repopulate the thymus of irradiated recipients. Using two color immunofluorescence, we demonstrate that the Pgp-1+ and IL-2R+ cells present in this enriched population represent largely nonoverlapping subsets, although some cells do express both markers. We also show by depletion of these two cell types that the bulk of the thymus-homing progenitors present in this enriched population are found in the Pgp-1+ population, and not in the IL-2R+ population. We discuss the relationship between the thymus-homing progenitors in this depleted thymus subpopulation and the thymus-homing progenitors present in the thymus as a whole. PMID- 3093092 TI - Modulation of lymphocyte proliferation and immunoglobulin synthesis by interferon gamma and "type I" interferons. AB - Interferon (IFN)-alpha and IFN-beta ("type I" IFNs), but not IFN-gamma reduced phytohemagglutinin- or pokeweed mitogen (PWM)-induced proliferation in cultures of human mononuclear leukocytes. Proliferation induced by specific antigens (tuberculin PPD or tetanus toxoid) or by exogenous interleukin 2 (IL-2) was strongly inhibited by type I IFNs and, to a lesser extent, by IFN-gamma as well. Inhibition of proliferation in mitogen-stimulated cultures was not due to a reduced production of IL-2 or to an inhibition of IL-2 receptor expression. Type I IFNs inhibited immunoglobulin (Ig) production in PWM-stimulated unseparated mononuclear cells, whereas IFN-gamma enhanced Ig production in such cultures. In cultures of purified B cells type I IFNs caused a stimulation of Ig production and this B-cell differentiation factor (BCDF)-like activity of IFNs was synergistically enhanced in the presence of IL-2. IFN-gamma produced less BCDF like activity than type I IFNs. These results show that in some instances type I IFNs can be more potent in affecting functions of cells of the immune system than IFN-gamma. PMID- 3093093 TI - Characterization of three different rat T-cell clones with specificity to Listeria monocytogenes: phenotype, specific proliferation, lymphokine production, and protective capacity in vivo. AB - Splenic T lymphocytes from rats immunized with the facultative intracellular bacterium, Listeria monocytogenes, were cloned by the limiting-dilution technique. From several clones obtained, three have been scrutinized in detail. As demonstrated by their reactivity to the monoclonal antibodies, W3/25 and MRC OX8, the clones RVIIC2 and R23D6 are of helper cell phenotype, whereas cells from clone R30D5 express both the helper and the cytotoxic/suppressor cell markers. Proliferation of all three clones critically depends on antigen-presenting cells, exogenous interleukin 2, Listeria antigen, and on class II-restricted antigen presentation by accessory cells. There are differences between cells from different clones with respect to the degree of production of migration inhibitory and macrophage-activating factors. Thus, T lymphocytes of clones R23D6 and R30D5 are highly active, whereas cells of clone RVIIC2 showed markedly less production of these factors. In vivo studies, analyzing the capacity of cells to transfer systemic protection, showed a positive correlation between the production of migration inhibitory factor, macrophage-activating factor, and systemic protection. PMID- 3093094 TI - 402AX teratocarcinoma MHC class I antigen expression is regulated in vivo by Lyt 1, Lyt 2, and L3T4 expressing splenic T cells. AB - The murine 402AX teratocarcinoma is a MHC class I antigen negative tumor of 129 strain origin. Host resistance to the 402AX tumor is genetically controlled. When passed intraperitoneally in genetically resistant mice, the tumor cells are induced to express MHC Class I antigens of the 129 genotype. When passed in genetically susceptible mice, the tumor cells remain MHC class I antigen negative. Earlier studies have demonstrated that resistance to the tumor and regulation of tumor cell MHC class I antigen expression are under the control of the host's immune system. The present studies indicate that splenic Lyt 1-, Lyt 2 , and L3T4-expressing cells regulate tumor cell MHC class I antigen expression, and that these cells require a genetically resistant host environment in which to differentiate. Splenic T cells primed to the 402AX tumor and transferred into genetically susceptible 129 mice give rise to GVHD, suggesting that immunity to the tumor involves reactivity to 129 minor histocompatibility antigens. PMID- 3093095 TI - Ornithine decarboxylase induction and polyamine biosynthesis are required for the growth of interleukin-2- and interleukin-3-dependent cell lines. AB - The objective of this study was to evaluate induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, and subsequent polyamine accumulation in interleukin-2 (IL-2)- and interleukin-3 (IL-3) dependent growth. The CTLL-20 and FDC-P1 cell lines, which have been shown to be absolutely dependent on IL-2 and IL-3, respectively, were used in these studies. The CTLL-20 and FDC-P1 cells each had different temporal patterns of ODC induction following lymphokine stimulation. ODC levels increased rapidly in the FDC-P1 cells, peaking 4 hr after stimulation with IL-3. In contrast, peak ODC activity in the CTLL-20 cells occurred 18 hr following stimulation with IL-2 and reached eightfold higher levels than those observed in the FDC-P1 cells. Treatment with D,L-alpha-difluoromethylornithine X HCl X H2O (DFMO), a specific irreversible inhibitor of ODC activity, completely abrogated lymphokine-dependent ODC induction in both the CTLL-20 and FDC-P1 cell lines. Similarly, intracellular levels of the polyamines putrescine and spermidine were reduced in both cell lines following DFMO treatment. DFMO treatment reduced both IL-2- and IL-3 dependent proliferation in a dose-dependent manner. However, this inhibition could be reversed by the addition of exogenous putrescine. DFMO treatment had no effect on cell viability. Polyamine-depleted CTLL-20 and FDC-P1 cells showed decreased absorption of IL-2 and IL-3 activity, respectively. However, the addition of exogenous putrescine restored the ability of the cells to absorb the appropriate lymphokine. These data are the first to demonstrate that ODC induction and polyamine biosynthesis are required in lymphokine dependent growth. PMID- 3093096 TI - A human T-T-cell hybridoma-derived lymphocyte chemoattractant factor. AB - Human T-T hybridomas were developed as a strategy for obtaining lymphokines that alter T-lymphocyte motility. Mitogen-stimulated human T lymphocytes were fused with cells of the human CEM lymphoma line and the supernatants derived from these fusion products were assessed for chemoattractant activity in a modified Boyden chamber assay. Supernatants from hybridoma 41B2 enhanced lymphocyte migration to 198 +/- 13% (mean +/- SEM) of control. Characterization by Sephadex G-100 molecular sieve chromatography revealed a single peak of chemoattractant activity corresponding to a molecular weight (MW) of 56,000. This activity eluted from a Sephadex QAE anion-exchange column at 4-6 mS. Subsequent isoelectric focusing in sucrose revealed an isoelectric point of 9.0-9.2. Fractions with activity after sequential molecular sieve and anion-exchange chromatography were concentrated, radiolabeled with 125I, and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography revealed a band which corresponded to a MW of 14,000 (representing four similar monomeric chains) and to the region from which chemoattractant activity could be detected in eluates from slices of unstained gels run in parallel. The biological activity of this hybridoma-derived lymphocyte chemoattractant was abolished by treatment with trypsin and neuraminidase but was unaffected by heating to 56 degrees C. We conclude that certain human T-T-cell hybridomas constitutively elaborate a lymphocyte chemoattractant that appears to be physicochemically identical to a previously described human lymphokine, lymphocyte chemoattractant factor. PMID- 3093097 TI - A low level of macrophages enhances anti-TNP plaque-forming cell generation by human lymphocytes against TNP-Brucella abortus, a T-independent antigen. AB - Making use of trinitrophenyl-Brucella abortus (TNP-Ba), a T-independent antigen, the mechanism of antibody production in vitro by human lymphocytes was studied, focusing on the accessory role played by macrophages (m phi). Human tonsillar cells and peripheral blood lymphocytes (PBL), and their fractions which were depleted of T cells, M phi, or both by rosetting with sheep erythrocytes and glass adherence plus passage through a Sephadex G-10 column, were stimulated in vitro with TNP-Ba under optimal culture conditions. Substantial antibody response against the antigen was induced in the whole tonsillar cells, while no appreciable level of response was induced in the whole PBL. The level of response observed after T-cell depletion was not different from that of the whole cells. In contrast, the response was significantly enhanced both in tonsillar cells and in PBL by depleting M phi to a low level, such as 1-2% of the cultured cells. It was further shown that a small amount of M phi added back to the M phi-depleted fraction activity suppressed the response again to the level seen in the whole cells. If allogenic M phi were substituted for autologous ones, the same degree of suppressor function was observed irrespective of the difference seen in the HLA types. PMID- 3093098 TI - Human thymocyte maturation in vitro: a flow cytometric analysis. AB - Using an in vitro culture system, light scatter analyses, and two-color flow cytometry, we provide evidence that the interleukin-2 (IL-2) and transferrin receptors can be induced within 48 hr on nonproliferating immature thymocytes. The thymocytes (greater than 35%) that expressed the transferrin and IL-2 receptors demonstrated nuclear activation as measured by log 90 degrees light scatter analysis. Increases in antigen-receptor-associated T3-antigen expression followed transferrin and IL-2-receptor induction and occurred on maximally activated T4+T8+ thymocytes on Day 3 of culture. Maximal T3 expression did not occur until Days 5-7 and paralleled loss of T4, T8 coexpression, suggesting an association between a mature T3-Ti antigen receptor complex and a mature T4, T8 phenotype. PMID- 3093099 TI - The in vitro bactericidal activity of peritoneal and spleen cells from Listeria resistant and -susceptible mouse strains. AB - Two days after Listeria-resistant (LrR) C57BL/10 mice were infected intraperitoneally with Listeria, their peritoneal macrophages demonstrated enhanced bactericidal activity beyond that seen in susceptible (LrS) BALB/c or CBA mice. Intravenous infection had no effect on peritoneal cell activity. The induction, but not expression, of the enhanced activity was radiosensitive. There was no significant difference between the strains with respect to the number of cells or cellular composition of the exudates. No difference in the in vitro chemotactic response of cells from the two strains could be demonstrated. Therefore there seems to be recruitment to the infected peritoneal cavity of C57BL/10 mice of young, efficiently bactericidal monocytes/macrophages. On the other hand, spleen cell bactericidal activity was intrinsically superior in C57BL/10 mice compared with BALB/c mice, possibly because, as a haemopoietic organ, the C57BL/10 spleen already contains high numbers of these efficient monocytes. PMID- 3093100 TI - Interferon-gamma enhances target cell sensitivity to monocyte killing. AB - The mechanism of human peripheral blood monocyte-mediated cytotoxicity was investigated using the HT-29 human colon adenocarcinoma line, A673 human rhabdomyosarcoma line, and A375 human melanoma line as target cells. Pretreatment of these target cells with 100 U/ml of recombinant human interferon (IFN)-gamma for 48 hr increased their susceptibility to monocyte killing. Increased susceptibility to the lytic action was particularly pronounced at low effector/target cell ratios. Unlike IFN-gamma human IFN-alpha did not potentiate monocyte cytotoxicity, and pretreatment of HT-29 with IFN-alpha also had virtually no effect on their susceptibility to monocyte killing. However, IFN gamma appeared to prime either monocytes or target cells to become responsive to IFN-alpha. Our data suggest that IFN-gamma can promote the killing of tumor cells by monocytes through two separate actions, one on the monocyte and one on the target cell. PMID- 3093101 TI - The role of monoclonal antibodies and the recombinant DNA technology in studying autoantibody production. AB - The hybridoma technology has made it possible to sample the B-cell repertoire and to generate monoclonal antibodies which can be analyzed for their specificity and idiotypy. Using the recombinant DNA technology, the structure of the genes which encode those antibodies can be analyzed. The knowledge gained from the application of these techniques has made it possible to pose specific questions about the origins of autoantibodies. PMID- 3093102 TI - Biochemistry and biology of antigen presentation by macrophages. AB - The presentation of antigen by macrophages has been studied. We have shown that globular proteins must be processed in endocytic vesicles of low pH prior to presentation. Some of the structural requirements of one such processed peptide have been determined, as has the affinity for Ia of that peptide. Finally, we have shown that a membrane-associated form of interleukin-1 is also required for presentation of processed antigen to T cells. PMID- 3093103 TI - Perspective on molecular immunology and modulation of immune responses. AB - Despite enormous advances made in recent years, there remain fundamental and fascinating unanswered questions in immunology. They would include the mechanism of tolerance, the biological significance of the major histocompatibility complex (MHC) restriction, generation of diversity in T cells, control of V region and isotype selection in B cells, how immune response genes work and how important their function is in man, among others. With the advent of monoclonal antibodies and recombinant DNA technologies, together with greater understanding of immunological interactions within the network and of the intracellular networks between membrane-associated receptors and cell function, a variety of immunological strategies are available for modulating immune responses in man. Some nonspecific strategies include immunomodulatory lymphokines, receptor modulation, and development of agonists and antagonists for important receptors. In addition, there is great potential for immunologically specific strategies for intervention, including the use of idiotypes and anti-idiotypes and genetic engineering of antibodies. Ultimately, there is the possibility of predicting antigenic epitopes likely to engage the cellular and humoral arms of the immune response on the basis of protein or DNA sequences. The potential of exploring these developments for new diagnostic tests and vaccines is emphasized here, as is the unpredictable importance of seemingly nonrelevant fundamental science in producing many of the tools for intervention, now and in the future. PMID- 3093104 TI - Regulation of B-lymphocyte activation, proliferation, and immunoglobulin secretion. AB - Lymphocyte growth and differentiation are controlled by signals resulting from the interaction of antigen and cellular products, such as lymphokines, with specific cell membrane receptors. Resting B lymphocytes can be activated by low concentrations (1-5 micrograms/ml) of antibodies to membrane IgM, which is the B lymphocyte receptor for antigen. The binding of anti-IgM to B cells causes a rapid increase in intracellular free calcium concentration ([Ca2+]i), in inositol phosphate concentration, and in protein kinase activity. Moreover, the effects of anti-IgM on B cells are mimicked by the combined use of calcium ionophores and phorbol esters. Since phorbol esters activate protein kinase c, this suggests that the increase in [Ca2+]i and in phosphatidylinositol metabolism stimulated by anti-IgM are critical events in B-cell activation. The entry into S phase of B cells stimulated with anti-IgM depends on the action of a T-cell-derived factor designated B-cell stimulatory factor (BSF)-1. This is a 20,000-Da protein which is a powerful inducer of class II major histocompatibility complex molecules. Although an important cofactor for B-cell proliferative responses to anti-IgM, its major locus of action is on resting B cells. B cells stimulated with anti-IgM and BSF-1 do not synthesize secretory IgM. However, if two additional T-cell derived factors, B151-TRF and interleukin-2, are added to cultures, a substantial proportion of stimulated B cells produce secretory IgM. BSF-1 has also been shown to participate in the "switch" in Ig class expression. Resting B cells cultured with lipopolysaccharide will switch to IgG1 secretion in the presence of purified BSF-1. PMID- 3093105 TI - Immunopathology of the lesion in chronic relapsing experimental autoimmune encephalomyelitis in the mouse. AB - To analyze immunopathologic events within the central nervous system (CNS) during various stages of actively induced chronic relapsing EAE in SJL/J mice, animals were sampled at various timepoints post inoculation (PI) and T cells, T-cell subsets, Ia+ cells and Ig+ cells, albumin, and Ig deposits were localized in frozen sections by immunocytochemical techniques. Furthermore, sections were stained for the demonstration of Ia antigen, myelin basic protein (MBP), and galactocerebroside (GC) on endothelial cells and astrocytes. During the acute phase of the disease, large numbers of all types of inflammatory cells studied (Lyt-1.2+, L3T4+, Lyt-2+, Ia+, Ig+) were randomly distributed throughout lesions, a finding similar to that described previously for acute EAE. A more distinct distribution pattern of infiltrating T cells was found during active chronic disease in that L3T4+ cells predominated within the CNS parenchyma, while Lyt-2+ cells were more numerous in meningeal and perivascular areas. During all chronic stages, a low-grade diffuse infiltration of the neuraxis by hematogenous cells was present. Ia and myelin antigens were detectable on some endothelial cells and astrocytes. Damage to the blood-brain barrier, as indicated by albumin and Ig deposits, was more extensive during the acute than during chronic stages of the disease. Taken in concert, the results further support the possibility of local antigen presentation on endothelial and astroglial cells and an essential involvement of helper (L3T4+) T cells in CNS lesion formation. These findings correlate well with events reported previously in acute and chronic multiple sclerosis lesions. PMID- 3093106 TI - Teratocarcinoma cell MHC antigen expression is regulated in vitro by a soluble noninterferon factor. AB - The 402AX murine teratocarcinoma is a spontaneous testicular tumor of 129 (H-2b) origin which does not express MHC encoded antigens. Rejection of this tumor is immunologically mediated and the tumor cells are induced in vivo to synthesize H 2b antigens when passaged in genetically resistant host mice. The present studies demonstrate that serum from tumor primed genetically resistant host mice can induce tumor cell MHC antigen expression in vitro as measured by indirect immunofluorescence using monoclonal antibodies. The inducing factor is specific for 402AX tumor cells and is not interferon as shown by the lack of response of the 402AX tumor to gamma interferon, and the absence of significant interferon activity in inducer serum. These studies demonstrate another factor independent of interferon that can induce MHC class I antigen expression on tumor cells. PMID- 3093107 TI - Structure and composition of the cytoskeleton of nucleated erythrocytes: III. Organization of the cytoskeleton of Bufo marinus erythrocytes as revealed by freeze-dried platinum-carbon replicas and immunofluorescence microscopy. AB - Platinum-carbon (Pt-C) replicas of freeze-dried erythrocyte cytoskeletons of the toad, Bufo marinus, were prepared using a modified Balzers 300 system. Examination in stereo of replicas of the microtubule-containing marginal band revealed filaments projecting from the microtubule walls to form links between adjacent microtubules. These cross-bridging proteins may bundle the microtubules into the configuration of the marginal band (MB) and may also serve to stabilize the structure. The MB appears to have linkages to components of the surface associated cytoskeleton (SAC). The SAC forms a continuous matrix that spreads across the upper and lower surfaces of the cell adjacent to the plasma membrane and extends around the outer perimeter of the MB. Thus, the SAC encapsulates the MB and the central nucleus. After lysis, the elements of the cytoskeleton remain in a configuration similar to that found in the whole cell. Spectrin (fodrin) and actin were identified by immunofluorescence in the region of the SAC. When labeled with antibodies specific for vimentin and synemin, a network of intermediate filaments can be detected in the region between the nucleus and the MB. These vimentin filaments are also enclosed within the SAC and appear in Pt-C replicas to emerge from the area of the nuclear envelope. As the filaments extend toward the periphery of the cell, they form attachments to the SAC. Attachments of intermediate filaments to both the nucleus and the SAC thus appear to anchor the nucleus in its central position within the cytoskeleton. PMID- 3093108 TI - A toxicity study of recombinant interferon-gamma given by intravenous infusion to patients with advanced cancer. AB - Eighteen patients with solid tumours were treated with human recombinant interferon-gamma at escalating dose levels starting at 1 X 10(6) units/m2 per infusion and rising through 3 X 10(6), 6 X 10(6), 9 X 10(6) and 22 X 10(6) to a maximum of 110 X 10(6) units/m2 per infusion. The IV infusions were given three times a week over a 4-week period. Side effects were seen in all patients, but were mild except at the highest dose. Acute dose-related effects included pyrexia, tiredness, thirst, chills and rigors. Chronic dose-related effects included anorexia, lethargy, weakness, disorientation, a trace of proteinuria and minimal rises in liver enzymes. In addition, effects were observed which were not related to dose. These included headache, nausea and vomiting, backache, myalgia, flatulence and a mild, transient reduction in neutrophils and erythrocytes. At the highest dose level dose-limiting toxicity was observed, consisting in severe tiredness and anorexia, hypotension, disorientation and changes on the electrocardiograph. Overall, toxicity was similar to that seen with preparations of interferon-alpha, except that no tolerance to the effects of interferon-gamma was noted. We observed less hepatic and haematological toxicity, but also recorded flatulence, handcramps and electrocardiograph changes, which have not been reported with interferon-alpha. When given according to this regimen, doses of 22 X 10(6) units/m2 per infusion of recombinant interferon-gamma were generally well tolerated by the patients. PMID- 3093109 TI - The enzymatic conjugation of glutathione with bay-region diol-epoxides of benzo[a]pyrene, benz[a]anthracene and chrysene. AB - The kinetics of the enzymatic conjugation of glutathione (GSH) with the anti diastereoisomers of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE), trans-3,4-dihydroxy-1,2-epoxy-1,2,3, 4 tetrahydrobenz[a]anthracene (BADE) and trans-1,2- dihydroxy-3,4-epoxy-1,2,3,4 tetrahydrochrysene (CDE) catalyzed by transferase 4-4 from rat liver have been compared. When the concentration of these diol-epoxides was varied (using 2 mM GSH) the apparent Vmax values were 560, 2100 and 1500 nmol/mg/min for (+/-)-anti BPDE, (+/-)-anti-BADE and (+/-)-anti-CDE, respectively, with corresponding apparent Km values of 11, 125 and 105 microM. The catalytic efficiency of transferase 4-4 in the GSH conjugation of (+/-)-anti-BADE and (+/-)-anti-CDE is thus approximately one-third of (+/-)-anti-BPDE (0.014 and 0.012 s-1 microM-1 respectively versus 0.042 s-1 microM-1). Similar non-linear Lineweaver-Burk plots were obtained with each diol-epoxide when the concentration of GSH was varied, and two apparent Km values of 0.02-0.04 and 0.4-0.9 mM GSH were estimated. The GSH-conjugates formed with the individual enantiomers of the racemic substrates used were resolved by h.p.l.c. The data indicate that with each diol-epoxide transferase 4-4 is highly selective (greater than or equal to 95%) towards the biologically most active (+)-enantiomer. PMID- 3093110 TI - Effect of aliphatic amides on oncogenic transformation, sister chromatid exchanges, and mutations induced by cyclopenta[cd]-pyrene and benzo[a]pyrene. AB - We examined the effects of the aliphatic amides isopropyl-valeramide (IVA) and allylisopropylacetamide (AIA) on oncogenic transformation and sister chromatid exchanges (SCE) induced by cyclopenta[cd]pyrene (CPP) and benzo[a]pyrene (B[a]P) in C3H/10T1/2 cells and on B[a]Pdiol-epoxide (BPDE)-induced mutation at the HGPRT locus in Chinese hamster ovary (CHO) cells. IVA and AIA significantly suppressed B[a]P and CPP transformation in vitro. Both amides were effective when given just prior to, simultaneously with, or 24 h after carcinogen exposure. On the other hand, IVA and AIA did not affect cytotoxicity, the frequencies of SCE induced by CPP or B[a]P, nor BPDE-induced mutations in CHO cells. These and previous results suggest that the mechanism of inhibition of transformation by IVA or AIA may be very specific and probably not related to the early initiation event in oncogenic transformation in vitro. PMID- 3093111 TI - Disposition of the naturally occurring antimutagenic plant phenol, ellagic acid, and its synthetic derivatives, 3-O-decylellagic acid and 3,3'-di-O-methylellagic acid in mice. AB - The effect of ellagic acid and some of its more lipophilic derivatives on the mutagenicity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10 tetrahydrobenz[a]pyrene was examined in Salmonella typhimurium TA100. Ellagic acid, 3,3'-di-O-methylellagic acid, 4,4'-di-O-methylellagic acid and 3-O decylellagic acid were found to have approximately equal antimutagenic activity. The tissue distribution and elimination of ellagic acid, 3,3'-di-O-methylellagic acid and 3-O-decylellagic acid were examined in CD-1 mice. Little or no ellagic acid (less than 1 nmol/g) was found in blood, lung or liver after the oral administration by gavage of 300 mumol of ellagic acid per kg body weight of after feeding 1% of ellagic acid in the diet for 1 week. Following the i.p. administration of 120 mumol/kg of ellagic acid, the blood and lung levels of ellagic acid were 15-20 nmol/g at 30 min after the dose, and the concentrations of ellagic acid decreased to 1-3 nmol/g at 6-8 h after the dose. A portion of the administered i.p. dose precipitated in the abdominal cavity. After i.v. administration, ellagic acid was eliminated very rapidly from blood, lung and liver, and approximately 70% of the administered dose was recovered in the urine and feces as free ellagic acid and its conjugates. At 2 h after an i.v. injection of 60 mumol/kg of ellagic acid, 46% of the dose was recovered in the urine as ellagic acid and its conjugates. Of this amount, about half was excreted as free ellagic acid and half was excreted as conjugates. An additional 25% of the dose was recovered in the feces (mostly as free ellagic acid) after 7 h. The disposition of 3,3'-di-O-methylellagic acid or 3-O-decylellagic acid after i.v. administration (32 mumol/kg) was examined and compared to the disposition of the same i.v. dose of ellagic acid. The concentrations of ellagic acid, 3,3'-di-O methylellagic acid and 3-O-decylellagic acid decreased rapidly in the blood, liver and lung, but the concentrations of 3-O-decylellagic acid in the lung throughout the experimental period (2-360 min) was on average 20- to 40-fold higher than the corresponding average concentrations of ellagic acid or 3,3'-di-O methylellagic acid. PMID- 3093112 TI - The effect of neighbouring bases on G-specific DNA cleavage mediated by treatment with the anti-diol epoxide of benzo[a]pyrene in vitro. AB - Three 5'-end-labelled double-stranded linear DNA fragments of defined sequence were treated with r-7, t-8-dihydroxy-t-9, 10-oxy-7,8,9,10 tetrahydrobenzo[a]pyrene (anti-BPDE). The DNA samples were then examined by gel electrophoresis both before and after denaturation and treatment with alkali. The extent of modification of deoxyguanosine (dG) residues was estimated from changes in electrophoretic mobility: at saturation less than 25% of the dG residues appeared to be modified by reaction with anti-BPDE. The determination of the sites of G-specific strand cleavage in a total of 0.5 kbp of DNA by sequencing gel electrophoresis showed that scission at dG residues is sequence specific and that whilst, for example, cleavage occurred at the central dG residues of all 5' CGG-3' (21/21), of all 5'-TGG-3' (14/14), of all 5'-TGT-3' (7/7) and of all 5' CGT-3' (5/5) sequences examined, it did not occur in any of the 5'-GGA-3' (0/12) or 5'-GGC-3' (0/15) sequences and only occurred rarely in the 5'-GGG-3' (1/48) and 5'-GGT-3' (2/11) sequences. No cleavage was found at internal dG residues within poly(dG)9 or poly(dG)18 sequences. The data may permit prediction of the sites of strand scission in DNA molecules of known sequence that have been modified by diol-epoxides of polycyclic hydrocarbons. PMID- 3093114 TI - Effect of benzo[a]pyrene-diol-epoxide-I on growth of nascent DNA in synchronized human fibroblasts. AB - In logarithmically growing cultures of human fibroblasts, benzo[a]pyrene-diol epoxide-I (BPDE-I) treatment inhibits both replicon initiation and DNA chain elongation. In this study we have focused on the effect of BPDE-I treatment on the growth of nascent DNA strands in synchronized human fibroblasts. Cells were collected at the beginning of the S phase by replating confluent cultures in the presence of aphidicolin for 24 h. At 1 h after release from aphidicolin, cells were incubated with [3H]thymidine for 10-15 min and treated with BPDE-I for 10 min. Following different periods of incubation with unlabeled thymidine, cells were lysed on top of alkaline sucrose gradients for analysis of the size distribution of nascent DNA and its average molecular weight. After a brief pulse with the radiolabeled precursor, a unimodal distribution of nascent DNA strands was observed in control cells. Upon chase this distribution was displaced to higher average molecular weights at an approximate rate of 1 X 10(6) daltons/min. Treatment with low doses of BPDE-I (less than 0.2 microM) did not decrease this rate. Indeed the nascent DNA in BPDE-I-treated cells appeared to grow faster than in control cells. This higher rate of DNA strand growth may be related to the inhibition of replicon initiation. Treatment with 0.3 microM or 0.7 microM BPDE I, which are doses that interfere with DNA synthesis in operating replicons in asynchronous cells, also inhibited the growth of nascent DNA strands in synchronized cells by 22 and 64%, respectively. Because of the simultaneous inhibition of replicon initiation, these values are probably underestimations of the total inhibition of DNA strand growth. The use of synchronized cells in this type of study should aid in the elucidation of mechanisms of replication of carcinogen-damaged DNA. PMID- 3093113 TI - Inhibition of benzo[a]pyrene-dependent mutagenesis and cytochrome P-450 reductase activity by copper complexes. AB - The superoxide dismutase (SOD) biomimetic copper(II) (3,5-diisopropylsalicylate)2 (CuDIPS) has been previously reported to inhibit the tumorigenicity of a polycyclic aromatic hydrocarbon (PAH) requiring metabolic activation. We have used the Ames Salmonella typhimurium revertant assay to survey the effects of CuDIPS and its analogs on the metabolic activation of the PAH benzo[a]pyrene (BP) by liver homogenates. Supplementation of homogenates from normal and Aroclor 1254 treated SENCAR mice with varied concentrations of CuDIPS resulted in a dose dependent noncompetitive inhibition of BP mutagenesis. Cytochrome P-450 reductase activity in liver homogenates and microsomal preparations was also inhibited by concentrations of CuDIPS possessing antimutagenic activity. Neither DIPS nor ZnDIPS, analogs of CuDIPS lacking SOD activity, inhibited mutagenesis or P-450 reductase activity. CuSO4, which has SOD activity, was almost as effective as CuDIPS on a molar basis in inhibiting mutagenesis and P-450 reductase activity. The inhibitory effects of CuDIPS and CuSO4 could not be attributed to their SOD activity since bovine liver superoxide dismutase, at a 100-fold excess of CuDIPS SOD activity, had no effect on their activity. Collectively these findings suggest that the in vitro antimutagenic activity of CuDIPS is independent of its salicylate structure and is mediated through a copper-dependent but non SOD associated inhibition of P-450 reductase activity. PMID- 3093115 TI - Xeroderma pigmentosum variant and normal fibroblasts show the same response to the inhibition of DNA replication by benzo[a]pyrene-diol-epoxide-I. AB - Xeroderma pigmentosum (XP) variant cells are characterized by an abnormal pattern of replication of DNA damaged by 254 nm radiation (u.v.). To see whether benzo[a]pyrene-diol-epoxide-I (BPDE-I) elicits the same response, we have compared the effects of u.v. and BPDE-I on DNA replication in XP variant and normal skin fibroblasts. Doses of u.v. that only affected replicon initiation in normal cells, inhibited DNA strand growth in the XP variant. These results were confirmed by measurements of the rate of growth of single-stranded nascent DNA in cells synchronized at the beginning of the S phase. Identical analyses using BPDE I, however, indicated that the two cell types were equally sensitive to the inhibitions of both replicon initiation and DNA strand growth. These results indicate that the XP variant phenotype cannot be recognized in vitro by the pattern of response of fibroblasts to the inhibition of DNA replication by BPDE I. PMID- 3093116 TI - Synergism of thrombolytic agents in vivo. AB - The existence of significant synergism between tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA), and between t-PA and urokinase in thrombolysis in vivo is described. In a quantitative preparation of thrombolysis, consisting of rabbits in which a blood clot was induced in the jugular vein with 125I-labeled fibrin, intravenous infusion over 4 hr of t-PA, scu-PA, or urokinase in amounts of 0.5, 1.0, or 2.0 mg/kg body weight resulted in significant thrombolysis (30% to 60%). The simultaneous infusion of t-PA and scu-PA or of t-PA and urokinase had a significantly greater (p less than .001) thrombolytic effect than could be anticipated on the basis of the added effects of each agents alone. However, no synergism was observed between scu-PA and urokinase. The observed alpha 2 antiplasmin consumption and fibrinogen breakdown after urokinase at higher doses did not occur with the equivalent thrombolytic combinations of t-PA and urokinase. The combined use of synergic thrombolytic agents in patients may permit a significant reduction in total administered doses, probably with elimination of the systemic activation of the fibrinolytic system and the concomitant fibrinogen breakdown that is unavoidable with the currently used thrombolytic doses of each agent. PMID- 3093118 TI - Presence of unsedimented precipitate in visually non-turbid supernates in the heparin-manganese method for HDL-cholesterol quantitation. AB - An inherent problem with the heparin-manganese precipitation procedure for high density lipoprotein-cholesterol (HDL-C) quantitation is the inability to sediment all the precipitated lipoproteins, especially in hypertriglyceridemic samples. This results in overestimation of HDL-C. Thus ultrafiltration has been recommended for turbid supernates. We have investigated 47 non-turbid supernates for possible presence of unsedimented precipitate. Optical turbidity in these samples was found to correlate with the serum triglyceride level. With ultrafiltration of the supernates, there was a significant decrease in cholesterol, optical turbidity and apoprotein A-I. The percent change in turbidity correlated with the percent change in cholesterol. There was also correlation between percent change in cholesterol and the prefiltration supernate turbidity. These results indicate that visually clear supernates may show optical turbidity; the turbidity is likely due to triglyceride-rich particles, which contain cholesterol; the fall in cholesterol with ultrafiltration is due to removal of these floating particles and some adsorbance of HDL particles to the filters. PMID- 3093117 TI - Selective enhancement of function of stunned myocardium by increased flow. AB - Although augmentation of flow does not improve the performance of normal myocardium, the hyperemic response after brief coronary occlusion is associated with transient hyperfunction in the previously ischemic region. In this study we assessed the effect of vasodilator-enhanced coronary blood flow on the systolic function of postischemic stunned myocardium. In 18 open-chest, anesthetized dogs the anterior descending artery was occluded for 5 min, followed by a 10 min period of reflow, repeated 12 times with a final 90 min recovery period. After the recovery period, either 0.06 mg/min dipyridamole (n = 6), 1 mg/min papaverine (n = 6), or 1.5 micrograms/kg/min nitroglycerin (n = 6) was infused intravenously for 15 min. Regional myocardial blood flow, which had returned to normal before administration of vasodilator, was increased 150% above baseline by dipyridamole and 80% by papaverine, but was unchanged by nitroglycerin. Segmental shortening decreased after repeated occlusions: from 17.5% to 0.9% in the group later treated with dipyridamole, from 18.6% to 6.7% in the papaverine group, and from 19.2% to-1.9% in the nitroglycerin group (p less than .005 for all groups). Segmental shortening increased to 8.8% after dipyridamole, 13.6% after papaverine, and 5.1% after nitroglycerin (p less than .05 for all groups), although the load-independent end-systolic pressure-length relationship (ESPLR) showed a significant shift to the left, reflecting enhanced performance, only after dipyridamole and papaverine. For all dogs combined, the percent improvement in ESPLR was correlated with the percent increase in flow (R = -.73, p less than .001). Performance was unchanged in the control region despite similar augmentation of flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093119 TI - Determination of histamine concentrations in plasma by liquid chromatography/electrochemistry. AB - Histamine was extracted from deproteinized plasma with Amberlite CG 50 weak cation-exchange resin (analytical recovery of [3H]histamine, 60.5%). The eluate was evaporated and histamine in the redissolved sample was condensed with o phthalaldehyde and 2-mercaptoethanol at pH 11.5. This adduct was separated by liquid chromatography under isocratic conditions and oxidized on a glassy carbon electrode at +0.4 V for electrochemical detection. 3-Methylhistamine was used as internal standard. As little as 0.45 pmol of standard histamine condensate was detected. The histamine concentration in 88 human plasma samples appeared to be normally distributed; its mean value was 7.20 (SD 2.61) nmol/L. Authentic and extracted histamine produced similar hydrodynamic voltammograms, and exogenous and endogenous histamine gave identical chromatographic characteristics with different mobile phases or different chromatographic columns. Standard and extracted histamine had similar degradation rates when samples were incubated with diamine oxidase (EC 1.4.3.6). Analytical recovery of known amounts of histamine added to pooled plasma was 97.7% (SD 22.3%). The inter- and intra-assay CVs for histamine determinations were 9.0% and 8.6%, respectively. PMID- 3093121 TI - Immunoturbidimetric techniques for quantifying apolipoproteins CII and CIII. AB - Immunoturbidimetric assays for determination of serum apolipoproteins CII and CIII (apo CII and CIII) were developed for use on the Cobas-Bio centrifugal analyzer with commercially available antisera and reference sera. Within-run and between-run imprecision (CVs) for apo CII was respectively 3.3 and 6.2%, and for apo CIII 2.75 and 5.2%. Addition to sera of as much as 50 g of hemoglobin or 0.15 g of bilirubin per liter did not interfere with determinations of apolipoproteins. Concentrations of apo CII and CIII were measured in sera from 40 normolipidemic and hyperlipidemic subjects by these immunoturbidimetric methods (x) and by radial immunodiffusion assays (y). Apo CII and CIII gave slopes of 0.93 and 0.86, y-intercepts of 7.4 and 9.5 mg/L, and correlation coefficients of 0.96 and 0.94, respectively. Reference intervals for the two apolipoproteins were established with sera from 100 normolipidemic subjects. The distribution of apo CII and CIII among the various lipoprotein fractions for normal subjects differed significantly (p less than 0.005) from that for hypertriglyceridemic subjects. PMID- 3093120 TI - Radioimmunoassay of metanephrine and normetanephrine for diagnosis of pheochromocytoma. AB - Sensitive and specific radioimmunoassays of metanephrine and normetanephrine were developed by use of 125I-labeled synephrine and specific metanephrine antibody, and 125I-labeled octopamine and specific normetanephrine antibody. Specific antibody for both metanephrine and normetanephrine was raised in rabbits by immunization with bovine serum albumin conjugated with the corresponding hapten, prepared by the method of Grota and Brown (Endocrinology 1976;98:615). The detection limits of the metanephrine and the normetanephrine radioimmunoassays were 2 and 6 pg/tube, respectively. Mean plasma metanephrine and normetanephrine values for 24 normal subjects were 62 (SD 14) and 100 (SD 40) ng/L, respectively. Mean urinary metanephrine and normetanephrine values for 22 normal subjects were 154 (SD 74) and 217 (SD 109) micrograms/day. For 14 pheochromocytoma patients, plasma metanephrine and normetanephrine values ranged from 29 to 683 and from 28 to 7850 ng/L, and urinary metanephrine and normetanephrine values were 606 to 6630 and 296 to 4800 micrograms/day, respectively. The present methods are simple and suitable for routine tests or for mass screening for pheochromocytoma. PMID- 3093123 TI - Islet transplantation. PMID- 3093122 TI - Detection and typing of serum paraproteins with the Quantimetric kappa:Lambda ratio test. PMID- 3093124 TI - Brain noradrenaline and the development of hypertension: the effect of treatment with central 6-hydroxydopamine or DSP-4. AB - The relative role of brain catecholamines in the development of hypertension in the spontaneously hypertensive rat (SHR) was studied. Treatments consisted in five weeks old SHR of central injections of 6-hydroxydopamine (6-OHDA), 3 X 200 micrograms either intracerebroventricularly (i.c.v.) or intracisternally (i.c.), or of intraperitoneal (i.p.) injections of DSP-4, either once or three times 50 mg/kg. Compared to the pronounced attenuation of the development of hypertension following i.c.v. 6-OHDA treatment, the i.c. 6-OHDA treatment and the multiple DSP 4 treatment were less effective. A single injection of DSP-4 had only minor effects on blood pressure. Heart rate was markedly lower in i.c.v. 6-OHDA treated SHR, but the other treatments induced no effects on this parameter. Noradrenaline depletion was found in various parts of the brain particularly after i.c.v. 6 OHDA or either DSP-4 treatment. Brain dopamine and adrenaline were depleted to a lesser extent. However, the best correlation between blood pressure and brain catecholamine concentration was found for dopamine in the hippocampus and hypothalamus and for adrenaline in the hypothalamus. Noradrenaline levels were also correlated with blood pressure, but to a lesser extent. These results suggest that the depletion of dopamine or adrenaline in the brain may be of more importance in the effects of neurotoxic treatments on the development of hypertension than the effects on brain noradrenaline. Thus, these experiments lend support to the hypothesis that brain noradrenaline systems may not play an important role in the development of hypertension in the SHR. PMID- 3093125 TI - Chest pain in acute myocardial infarction: a descriptive study according to subjective assessment and morphine requirement. AB - In 722 patients with suspected acute myocardial infarction (MI) we have tried to describe the course of chest pain according to their own assessment and morphine requirement. Patients were asked to score pain from 0-10 every second hour after arrival in the coronary care unit (CCU) and also to score their maximal pain at home. A very high intensity of chest pain was observed at home (mean score 7.1). At arrival in the CCU the mean pain score already had declined to 1.8, although 51% still had chest pain. Pain score declined successively during the first 12 hours in the CCU. At 24 hours after arrival, 20% still had some chest discomfort. In one quarter of the series a score of more than 0 was observed later than 24 hours after arrival in CCU. Patients developing definite MI had, as expected, a longer duration of pain and a much higher requirement of morphine compared with those with no MI. The difference between MI and no MI patients regarding subjective assessment of the initial intensity of pain at home and in hospital was, however, surprisingly low. PMID- 3093126 TI - Alterations in microsomal drug metabolism and heme oxygenase activity in isolated hepatic parenchymal and sinusoidal cells in Murphy-Sturm lymphosarcoma-bearing rats. AB - Previous studies have demonstrated that Murphy-Sturm lymphosarcoma-bearing rats have significantly decreased hepatic microsomal cytochrome P-450 and NADPH cytochrome c reductase activity, a consequent decreased capacity for oxidative microsomal drug metabolism, and increased microsomal heme oxygenase activity. Splenic microsomes obtained from tumor-bearing rats did not display similar changes. To define the cellular locus of these changes, preparations of hepatic parenchymal and hepatic sinusoidal cells were obtained from control and Murphy Sturm lymphosarcoma-bearing rats and examined for alterations in microsomal parameters of drug metabolism and heme oxygenase. In hepatic parenchymal cell populations, heme oxygenase activity was significantly increased in tumor-bearing rats (0.046 nmol/mg/min vs. 0.019 nmol/mg/min, control, p less than 0.01) while other microsomal parameters were all significantly decreased in activity (cytochrome P-450, 0.25 nmol/mg vs 0.70 nmol/mg, control, p less than 0.001; NADPH-cytochrome c reductase, 24.4 nmol/mg/min vs 42.6 nmol/mg/min, control, p less than 0.005; benzo(a) pyrene hydroxylase, 0.230 nmol/mg/min vs. 0.518 nmol/mg/min, control, p less than 0.001). These results are similar to those obtained with microsomes from whole liver. Conversely, while hepatic sinusoidal cell preparations also demonstrated increased heme oxygenase activity (0.134 nmol/mg/min vs 0.079 nmol/mg/min, control, p less than 0.01), all other hepatic sinusoidal cell microsomal parameters were not appreciably altered in tumor bearing animals. The results indicate that the major effect of the tumor-bearing state on hepatic microsomal heme and drug metabolism is on the parenchymal cell, and not the sinusoidal cell population. PMID- 3093127 TI - Adaptation of intestinal sugar and amino acid transport to gastric hyperalimentation. AB - These studies were undertaken to analyze the effects in dogs of the administration of liquid polymeric diets by gastric tube for 14 days on brush border absorptive functions measured in vitro. Transport studies of D-glucose, L leucine and L-alanine have been performed by a rapid filtration technique using brush border membrane vesicles isolated from different segments of the small intestine in order to get insights about events occurring directly at the membrane level. Our results clearly show that only the Na+ -gradient dependent pathways for sugars and neutral amino acids transport were modified in treated dogs as compared to chow-fed controls. The adaptation to the diets varied according to the intestinal segment considered and the effects were dependent on both the nature of the diet and the transport function analysed. These effects cannot be due to heterogeneity in the populations of vesicles isolated in the different situations and cannot be attributed to a modification of either the passive permeability of the membrane to solutes or ions or the membrane potential. Our results are best explained by changes in carrier densities along the small intestine in response to modification in the local concentrations of nutrients sequential to faster flow rates in the small intestine. The liquid nature of the polymeric diets, combined with their high fat and low residue content as compared to dog chow, could act in concert to promote faster rates of gastric emptying and intestinal transit, thus leading to modifications in nutrient availability along the small intestine. PMID- 3093128 TI - Immune and non-immune hydrops. PMID- 3093130 TI - Lysosomes and pancreatic islet function: intracellular insulin degradation and lysosomal transformations. AB - Previous observations indicate that substantial amounts of insulin are degraded intracellularly in isolated pancreatic islets exposed to low or physiological glucose concentrations. The intracellular degradation of insulin seems to occur by a crinophagic process. The aim of the present investigation was to elucidate the role of glucose both in the intracellular insulin degradation and in the lysosomal changes associated with crinophagy in the pancreatic islets. Isolated islets were maintained for 1 week in tissue culture at glucose concentrations of either 3.3 or 28 mmol/l. At both glucose concentrations experimental conditions producing both low and high rates of insulin secretion were examined. Differences in intracellular insulin degradation between the low and high insulin secretory conditions were estimated by measuring insulin biosynthesis and the total amounts of intracellular and extracellular insulin in the islet cultures. Primary and secondary lysosomes in the islets were strictly defined by morphological criteria and evaluated by ultrastructural morphometry. The intracellular degradation of insulin was significantly enhanced in the low-secretory conditions, irrespective of the glucose concentration. Also at both glucose concentrations, primary lysosomes occurred with higher frequency in islets with a high insulin secretion, whereas secondary lysosomes predominated in islets with a low rate of secretion. Thus, the degradative process is manifested as a transformation of lysosomes from their primary to their secondary form. Furthermore, it is suggested that glucose does not interfere directly with crinophagy but rather affects intracellular degradation of insulin in the pancreatic B cells by changing retention of secretory material. PMID- 3093129 TI - Poor correlation between single-dose data and steady-state kinetics for phenobarbitone, primidone, carbamazepine and sodium valproate in children during monotherapy. Possible reasons for the lack of correlation. AB - An investigation was performed to determine the relationship between the serum drug concentration/dose ratio at 24 hours following a first dose and that at steady-state for phenobarbitone, primidone (as phenobarbitone and as primidone), carbamazepine and sodium valproate, in order to assess the utility of this method in clinical practice. The drugs were given as monotherapy to 63 children for the treatment of epilepsy or febrile convulsions. The correlation between concentration/dose ratios, instead of between serum concentrations, was investigated with the aim of allowing the use of variable doses. The correlation coefficients were: r = 0.30 for phenobarbitone; r = 0.05 for phenobarbitone derived from primidone; r = 0.38 for primidone; r = 0.19 for carbamazepine; and r = 0.52 for sodium valproate. None of these correlation coefficients differed statistically from 0. These low correlation coefficients contrast with the acceptable results found by other authors for other drugs, indicating that several factors may have a greater influence on this correlation than earlier investigations suggest. The poor correlation obtained emphasises the need for clinical verification of mathematical models based on theoretical considerations which do not always apply in practice. PMID- 3093131 TI - Radical treatment of prostatic carcinoma by megavoltage X-ray therapy. AB - The case records of 116 patients treated with radical megavoltage X-ray therapy for carcinoma of the prostate have been reviewed. The age-corrected actuarial 5 year survival rate was 60.0% and the 10-year rate was 31.5%. Multivariate analysis demonstrated that T classification was the strongest prognostic variable but a long delay between diagnosis and radiotherapy also had a detrimental effect on prognosis. The incidence of severe acute and late radiation morbidity was low. Radical radiotherapy has been shown to be a safe and effective form of management for localised carcinoma of the prostate. PMID- 3093132 TI - Early ureteric changes in Schistosoma haematobium infection. AB - Radiological findings were analysed in 56 young patients with proven Schistosoma haematobium infection. In 31 patients (55%) changes were present in both the bladder and the ureters but in seven patients (13%) only ureteric changes were seen. Hypertrophy of the mucosa, mild stenosis, linear calcification, punctate calcification or 'ureteritis calcinosa' and polyps are highly suggestive features of an early involvement of the upper urinary tract in this insidious disease. PMID- 3093133 TI - Kidney protection by pretreatment with free radical scavengers and allopurinol: renal function at recirculation after warm ischaemia in rabbits. AB - Renal function and morphology were studied before and after 60 min of renal ischaemia and contralateral nephrectomy in five groups of rabbits. The animals were pretreated with superoxide dismutase, catalase, allopurinol or mannitol. One group was not pretreated and served as a control. A moderate transient increase in serum creatinine concentration was observed in the control rabbits, while a significantly less pronounced increase was noted after pretreatment with superoxide dismutase, catalase and mannitol. Pretreatment with allopurinol did not significantly reduce the postoperative increase in serum creatinine and sodium excretion, but the urine osmolality returned to normal more rapidly than in the control group. The appearance under the light microscope of kidney tissue taken from surviving rabbits was found to be normal irrespective of pretreatment. Severe tubular necrosis was observed in the kidneys from rabbits that died during the observation period. PMID- 3093134 TI - Palmitic acid oxidation and incorporation into triglyceride by needle liver biopsy specimens from control subjects and patients with alcoholic fatty liver disease. AB - A micro-technique was developed to measure fatty acid oxidation in vitro and to investigate its possible derangement in alcoholic fatty liver disease. Percutaneous liver biopsy specimens were obtained from nine control subjects and 28 alcoholic patients with mild to severe fatty liver. Fresh tissue (10-15 mg) was incubated at 37 degrees C for 90 min in a sealed reaction flask containing 1.92 mmol/l [1-14C]palmitic acid (1-2 microCi) and 1% essentially fatty acid free albumin in Krebs-Henseleit buffer, pH 7.4. Radiolabelled CO2 and perchloric acid soluble ketone bodies were isolated and counted. CO2 production was markedly reduced in alcoholic patients with mild and severe fatty liver compared with controls. This depression was reversed by the addition of malate to the reaction flask but not by carnitine or coenzyme A. Ketone body production was similar in controls and patients with mild and severe fatty liver. After the incubation in vitro, the tissue was extracted with chloroform/methanol and the triglyceride fraction isolated by thin layer chromatography and counted for radioactivity. The rate of palmitic acid incorporation into triglyceride was higher in alcoholic patients, particularly those with severe fatty infiltration, compared with controls. It is suggested that alcoholic fatty liver is accompanied by a progressive reduction in palmitic acid oxidation with the major defect occurring in the tricarboxylic acid cycle. In contrast, the rate of palmitic acid esterification into triglyceride is enhanced. PMID- 3093135 TI - Ageing and the aggregating proteoglycans of human articular cartilage. PMID- 3093136 TI - Pure red cell aplasia and thymoma: demonstration of persisting inhibition of erythropoiesis after thymectomy and resolution after immune suppressive treatment. AB - A 61 year-old woman presented with general malaise, hair loss, pure red cell aplasia (PRCA) and thymoma: no growth of erythropoietic colonies in vitro (BFU-E) was observed in the presence of her own serum. The thymoma was removed: after the operation no improvement of her anaemic condition was observed and colony growth was very poor, although T-depleted narrow preparations showed a modest BFU-E formation in autologous serum. Following treatment with azathioprine, a complete recovery was seen, associated with normal BFU-E formation in vitro. This observation suggests that a complex inhibition of erythropoiesis may operate in PRCA involving both humoral and cellular factors; thymectomy alone may not be sufficient to restore haemopoiesis, but has to be followed by immune suppressive treatment. PMID- 3093137 TI - A study on the value of red cell exchange transfusion in transfusion dependent anaemias. AB - We compared red cell exchange transfusions (RC Ex) on the Aminco Celltrifuge (continuous flow cell separator) with conventional transfusions in 17 patients aged between 7 and 24 years who have transfusion dependent homozygous beta thalassaemia and two other patients with chronic transfusion dependent anaemias aged 20 and 22. We aimed to return the youngest cohort of cells ('Neocytes') from both donor blood and the patient and to discard older cells ('gerocytes'). Using RC Ex, red cell transfusion requirement was reduced by 30%, reducing significantly the iron load, and the transfusion interval was increased by 43%. There is a great demand by the patients to continue this therapy as they have appreciated the immediate benefit of reduced hospitalization. PMID- 3093138 TI - Coagulation factor activity in platelet concentrates stored up to 7 days: an in vitro and in vivo study. AB - The in vitro and in vivo recovery of coagulation factor activity in platelet concentrates stored up to 172 h was studied. In vitro studies revealed that fibrinogen and antithrombin III levels do not change with storage. Factors II, V, VII, VIII, IX, X and XI all showed statistically significant falls from baseline over the 172 h storage period. However, most factor activities remained above 70%, with the major exception of factors V and VIII. These factors fell to less than 30% activity over the storage period, consistent with their known lability during whole blood storage. In vivo studies after platelet concentrate infusion in patients with concurrent thrombocytopenia and coagulation deficiencies revealed that the measured in vitro activity was recoverable in vivo. We conclude that platelet concentrates stored for 172 h are an adequate source of clotting factors. However, like stored whole blood, they may not provide therapeutic doses of factors V and VIII. PMID- 3093139 TI - The UK National External Quality Assessment Scheme in Blood Group Serology. ABO and D grouping and antibody screening 1982-1983. AB - In seven surveys of blood grouping the overall rates of major error were 0.12% and 0.37% for uncomplicated ABO and D grouping respectively. Of 17 errors of ABO grouping, 13 were errors of transposition or interpretation and four were apparently technical. Of 52 errors of D grouping, 20 appeared to be errors of transposition or interpretation and 32 were apparently technical. Of the 32 technical errors of D grouping, 31 were D-negative grouped as Du (29) or D positive (2) and most of these errors were due to misgrouping in the antiglobulin test. Causes of error in D grouping by antiglobulin test include anti-Bg and other contaminating immune antibodies, residual unabsorbed anti-A and the inherently high rate of false positive results obtained in the antiglobulin test. In view of the lack of benefit of Du testing to blood recipients or to pregnant women and of the possible adverse consequences of misgrouping D-negative patients as Du or D-positive, it is recommended that Du testing be abandoned in these groups of patients. The surveys of antibody screening demonstrated lack of standardisation and error rates similar to those previously reported in the UK for compatibility testing. PMID- 3093140 TI - [Role of liver biopsy in the diagnosis and therapeutic management of liver diseases]. PMID- 3093141 TI - [Clinical neuropharmacology of antiepileptic agents in childhood]. PMID- 3093142 TI - Isolation of rat epidermal growth factor (r-EGF): chemical, biological and immunological comparisons with mouse and human EGF. AB - Rat epidermal growth factor, (r-EGF), was isolated from adult male rat submandibular glands, with final yields of 4-6 mg r-EGF from 20 to 25 g wet weight of tissue. Amino acid analysis of r-EGF indicated a high degree of homology with murine EGF (m-EGF) and human EGF, (h-EGF). However, r-EGF contains 49 amino acid residues, versus 53 for human and murine EGFs, and lacks two characteristic tryptophan residues present in the other two species. The lack of tryptophan residues did not affect cellular binding or mitogenic activity or r EGF. Polyclonal antisera to each of the three separate species demonstrated crossreactivity with the other species of EGF. A sensitive radioimmunoassay was developed for r-EGF which can detect 25 pg of hormone. PMID- 3093143 TI - Effects of 4-nitroquinoline 1-oxide on the DNA-protein complex. AB - The effects of 4-nitroquinoline 1-oxide (4NQO), a well known carcinogenic compound, on the DNA-protein complex and DNA Folding Proteins were investigated. FM3A cells were treated with 10(-6) M or 10(-5) M 4NQO for 30 min. Treatment with the 10(-6) M concentration was confirmed to cause the sedimentation of the DNA protein complex to become slower. DNA Folding Proteins were then isolated from 4NQO-treated and untreated control cells and analyzed by SDS-polyacrylamide gel electrophoresis. No appreciable differences in the amounts of the major components of DNA Folding Proteins could be found due to 4NQO-treatment, but the 92 K protein was induced in DNA-protein complex by treatment with 4NQO. PMID- 3093144 TI - A comparative study of hepatic and epidermal histidase in the guinea-pig (Cavia porcellus). AB - Histidine ammonia lyase was purified to homogeneity from guinea-pig liver and epidermis. Both enzymes had similar molecular weights, subunit composition and pH optima. Km values for the two were similar at pH 9.2 but different at pH 7.0. Both enzymes were stimulated by low thiol concentrations and inhibited at higher concentrations, but to different extents. Antibody to the hepatic enzyme showed complete identity against hepatic enzyme but incomplete identity against epidermal enzyme. PMID- 3093145 TI - Structural and functional properties of Drosophila melanogaster phosphorylase: comparison with the rabbit skeletal muscle enzyme. AB - Glycogen phosphorylase isolated from Drosophila melanogaster contains one pyridoxal 5'-phosphate per subunit; the coenzyme is in a hydrophobic environment. Fruit-fly phosphorylase a has lower KM for glucose-1-phosphate and is less sensitive to allosteric inhibitors than the b form of the enzyme. The amino acid composition of Drosophila phosphorylase differs from that of rabbit skeletal muscle phosphorylase. These two enzymes give distinct one dimensional peptide maps. The distribution of reactive SH-groups is markedly different in the insect and vertebrate phosphorylase. Fruit-fly phosphorylase a is dephosphorylated by either rabbit or Drosophila protein phosphatase-1 at a slower rate than rabbit muscle phosphorylase a. PMID- 3093146 TI - Pharmacokinetic studies with a vaginal delivery system releasing levonorgestrel at a near zero order rate for one year. AB - Vaginal rings releasing approximately 20 micrograms levonorgestrel per 24 hours were used continuously by ten women for a period of one year. Circulating plasma levels of levonorgestrel (L-NOG) were measured every second week. Steroid hormone binding globulin (SHBG) levels were measured in the first and last four blood samples drawn. A linear relationship between the logarithms of L-NOG concentrations and duration of use was found, indicating an exponential character of decrease in L-NOG levels during the study year. An average of 72% of the mean initial levels of L-NOG was found in the circulation after 6 months' and 52% after one year's use. The L-NOG levels decreased daily by 1.1 pmol/l (0.13%) on the average. The SHBG levels were not influenced by the long-term exposure to L NOG. The initial SHBG levels were significantly correlated (r = 0.88; P less than 0.001) to the initial L-NOG levels. The rings were well tolerated. Only in two of the ten subjects did the average number of bleeding days per month increase from a pretreatment value of 4.5 days per month to 8.3 and 9.5 days per month, respectively. PMID- 3093147 TI - Golgi and secreted galactosyltransferase. AB - Galactosyltransferase (GT) belongs to the glycosyltransferases. In several tissues and cell lines, the enzyme is localized by immunocytochemistry to the two to three trans cisternae of the Golgi complex and may thus be considered a specific membrane component of this type of endomembrane. As a consequence, it is the most common Golgi "marker" enzyme in cell fractionation studies. Study of its biosynthesis, membrane orientation, and turnover in several tissues and cultured cell lines has broadened our knowledge about Golgi function itself. The enzyme is oriented towards the lumen of the cisternal space. In this orientation, it catalyzes the transfer of galactose to glycoprotein-bound acetylglucosamine and, in the presence of alpha-lactalbumin, to glucose, as shown in the Golgi complex of mammary gland epithelial cells. The enzymatic properties of GT are well known. The metabolism of GT has been extensively studied in HeLa and human hepatoma cells. The enzyme is synthesized in the rough endoplasmic reticulum (RER) and provided with one N-linked oligosaccharide and palmitate residues. In the Golgi complex, terminal sugars are attached to the N-linked oligosaccharide and extensive O-glycosylation takes place. The half-life of the enzyme is about 20 hr, after which a soluble form appears in the culture medium. Release of GT into the medium is observed in all cell lines studied. This phenomenon is in accordance with the presence of soluble GT in body fluids such as serum, ascites, milk, and saliva. In patients suffering from ovarian and breast cancer, increased levels of GT enzyme activity have been reported. Whether extracellular GT is of biological significance is still a point of discussion. PMID- 3093148 TI - Ventilatory responses to carbon dioxide in infants at risk for sudden infant death syndrome. AB - We examined the ventilatory response to inhaled CO2 in 77 infants at postconceptional ages ranging from 31 to 50 wk, 43 of whom were also evaluated with a 12-h pneumocardiogram (PCG). Infants were tested after sedation with chloral hydrate, and monitored with ECG and transcutaneous oxygen and CO2 monitors. Sleep state was evaluated by visual inspection of the infant's behavior. Among the 43 infants examined with the PCG, 22 had abnormal PCGs. Of these, 27% had significantly (p less than .05) abnormal CO2 response slopes, compared to 9% of those with normal PCGs. Breathing frequency did not change after CO2 inhalation in 82% of the abnormal PCG and in 33% of the normal PCG groups. PMID- 3093150 TI - Simple and accurate monitoring of end-tidal carbon dioxide tensions during high frequency jet ventilation. AB - To determine whether end-tidal carbon dioxide tension (PETCO2) accurately reflects PaCO2 during high-frequency jet ventilation (HFJV), 43 studies were performed on eight mongrel dogs with normal lungs. During HFJV, minute volume was modified to obtain a range of PaCO2 values from 15.5 to 74.5 torr. When PETCO2 was measured with an infrared gas analyzer, there was a poor correlation between PaCO2 and PETCO2 values. However, when the high-frequency ventilator was adjusted to deliver large tidal-volume (sigh) breaths, PETCO2 values were significantly (r = 0.94, p less than .001) correlated with PaCO2. Our data suggest that the PETCO2 of alveolar gas is an accurate indicator of the PaCO2 during HFJV in nondiseased lungs. PMID- 3093149 TI - Bronchopleural complications of nasogastric feeding tubes. AB - Enteral alimentation via small soft feeding tubes is becoming more common as the importance of nutrition is recognized in the debilitated patient. The monofilament wire stylets that stiffen these tubes during their insertion may cause potentially lethal bronchopleural complications unless correct insertion techniques are used and the tube's position is carefully checked before starting enteral nutrition. PMID- 3093151 TI - Wheat germ agglutinin and concanavalin A binding during epithelial wound healing in the cornea. AB - It has been hypothesized that there are differences between membrane-associated glycoconjugates of wounded (migrating) epithelium and those of nonwounded (stationary) epithelium. To test this hypothesis, wheat germ agglutinin-ferritin (WGA-Fe) and concanaval in A-ferritin (Con A-Fe) binding to apical membranes of wounded and nonwounded rabbit corneal epithelia were compared. Epithelial abrasions of the superior half of the cornea were allowed to heal in vivo for six hours. Fixed corneas were then incubated with lectin-ferritin and prepared for electron microscopy. Measurements (ferritin particles per linear um of membrane) of WGA-Fe indicated that binding to leading cells (40.7 particles/um), to areas 20 to 35 cells behind the leading edge (46.5 particles/um) and to nonwounded epithelium (45.1 particles/um) from contralateral eyes were not significantly different. A competitive inhibitor of WGA, 0.2M N-acetylglucosamine, however, blocked 94 percent of WGA binding on leading cells (2.3 particles/um), while binding persisted in areas behind the leading edge (39.5 particles/um) and on nonwounded epithelium (43.6 particles/um). This indicates that leading cell surfaces have a weak affinity for WGA. Unlike WGA, Con A showed a distinct preference for leading-edge cells (33.9 particles/um) compared to nonwounded epithelium (9 particles/um). In areas 20-35 cells behind the leading edge, Con A binding was intermediate to these two extremes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093152 TI - Cardiopulmonary stress testing. A review of noninvasive approaches. AB - With readily available techniques, cardiopulmonary exercise testing permits noninvasive measurement of such parameters as heart rate, cardiac output, oxygen saturation, ventilation, and gas exchange to bring out abnormalities which are either underestimated or not detectable at rest. These parameters may be used to characterize a patient's primary limitation of exercise tolerance as either cardiac or pulmonary in origin. They can also provide precise data to assess response to treatment. Pulmonary gas exchange is evaluated primarily by measurement of oxygen consumption, carbon dioxide production, and ventilation over time. The relationship of these parameters to one another changes throughout the course of incremental exercise testing. By appreciating these basic relationships, the more complex abnormalities found in disease states can be understood. PMID- 3093154 TI - In vitro activity of aryl fluoroquinolones, Abbott 56619 and Abbott 56620, compared to ciprofloxacin, norfloxacin and beta-lactams versus multidrug resistant Enterobacteriaceae and Pseudomonas aeruginosa. AB - The new aryl fluoroquinolones, Abbott 56619 and Abbott 56620, were compared to ciprofloxacin, norfloxacin and newer beta-lactam agents in standardized microtiter testing versus multidrug-resistant gram-negative bacilli. Ciprofloxacin, followed by Abbott 56620, was generally the most active quinolone and imipenem the most active beta-lactam agent. PMID- 3093153 TI - Effect of 5-fluorouracil, mitoxantrone, methotrexate, and vincristine on the antibacterial activity of ceftriaxone, ceftazidime, cefotiam, piperacillin, and netilmicin. AB - Using the checkerboard agar dilution technique, antibacterial activity and in vitro interactions of 4 antineoplastic agents and 5 antimicrobial drugs were examined against 56 strains of 7 bacterial species. 5-fluorouracil was found to inhibit all strains of Staphylococcus aureus and of Staphylococcus epidermidis at a concentration of 0.8 micrograms/ml or less. 84% of all gram-negative strains were inhibited synergistically when 5-fluorouracil was combined with beta-lactam antibiotics. Methotrexate and cefotiam were antagonistic in 42% of all combinations, especially when tested against Escherichia coli and Klebsiella pneumoniae. PMID- 3093155 TI - Leukemia of the nervous system. A clinical analysis of 22 cases. PMID- 3093156 TI - CSF and plasma noradrenaline levels in acute cerebrovascular disease. PMID- 3093158 TI - Maple syrup urine disease in Chinese. PMID- 3093157 TI - Newborn screening for phenylketonuria in eleven districts. PMID- 3093159 TI - Surgery in early cancers of uterine cervix. A long-term follow-up study of therapeutic effects in 271 cases (1955-1977). PMID- 3093160 TI - Ultrastructural investigation of experimental fracture healing. Role of osteogenesis played by fibroblasts. PMID- 3093161 TI - Continuous direct current in the treatment of nonunion and delayed union. PMID- 3093162 TI - Surgical treatment of gastric cancer in China. An analysis of 11,734 cases. PMID- 3093163 TI - Biliary ascariasis. Endoscopic worm removal under radiological versus ultrasonic control. PMID- 3093164 TI - Endocrine diseases with dermatomyositis. PMID- 3093165 TI - Effect of external factors on fetal liver hemopoietic proliferative activity. PMID- 3093166 TI - Diagnosis and treatment of the primary sclerosing cholangitis in children. PMID- 3093167 TI - Preliminary studies on shared antigens among cercaria, adult worm and egg of Schistosoma japonicum. PMID- 3093168 TI - Restandardization of DDST from six cities in north China. The Collaborative Study Group of Child Developmental Test. PMID- 3093169 TI - Muscle transfer for paralysis of gluteus muscles after poliomyelitis. PMID- 3093170 TI - Tumors of the small intestine. Report of 131 cases and review of 1,024 cases in the literature. PMID- 3093171 TI - Excision-alcohol-replantation (EAR) method for bone grafting after tumor resection. PMID- 3093172 TI - Calcium buffering capacity of human seminal plasma: the role of EGTA in stimulating sperm motility. AB - The role of EGTA in stimulating human sperm motility (reported in Lancet i: 460 461, 1984) was investigated by measuring the calcium buffering capacity of human seminal plasma. Human seminal plasma contains 9.5 +/- 1.1 mM (mean +/- SE) calcium of which 0.16 +/- 0.01 mM only exists as free Ca2+. The free Ca2+ concentration was not changed by the addition of either 1 mM CaCl2 or 1 mM EGTA. The ability of seminal plasma to bind calcium ions was determined by adding varying amounts of CaCl2. Scatchard analysis of the results indicates the presence of high amounts of high-affinity (Kd1 = 3.4 +/- 0.2 microM, Bm1 = 11.5 +/- 1.5 mM) and low-affinity (Kd2 = 0.55 +/- 0.04 mM, Bm2 = 30.4 +/- 1.7 mM) Ca2+ complexing agents. The low-affinity Ca2+-binding substance may be citrate. These results seem to suggest that human seminal plasma has a high Ca2+ buffering capacity and the stimulation of sperm motility by EGTA ought to be mediated via a mechanism other than the reduction of the free calcium concentration in semen. PMID- 3093174 TI - [A study on praziquantel treatment of schistosomiasis]. PMID- 3093173 TI - Detection of bromodeoxyuridine incorporation in mammalian chromosomes by a bromodeoxyuridine antibody. II. Demonstration of sister chromatid exchanges. AB - A commercially available bromodeoxyuridine (BrdUrd) antibody was used to demonstrate sister chromatid differentiation (SCD) and to evaluate sister chromatid exchanges (SCEs) in V79 Chinese hamster cells. V79 cells were cultivated for one cell cycle in the presence of BrdUrd, followed by a second cell cycle in the absence of BrdUrd. Chromosome preparations were stained by a common immunologic staining technique. The staining pattern observed is similar to that after FPG (fluorescent plus Giemsa) staining, though with reverse staining specificity. The sensitivity of BrdUrd detection is enhanced by a factor of 20 compared to the FPG technique and thus allows the evaluation of SCEs at very low BrdUrd concentrations. The application of the antibody technique gives information about the origin and localization of SCEs and produces further evidence for the spontaneous occurrence of SCEs. PMID- 3093175 TI - [Praziquantel and its levo-and dextro-isomers for the treatment of rabbits infected with schistosomiasis japonica]. PMID- 3093176 TI - [Studies on the induction of alpha and gamma interferon in chronic hepatitis B patients]. PMID- 3093177 TI - [Substrate interaction in post-traumatic low-calorie parenteral nutritional support]. PMID- 3093178 TI - A method to average immunofluorescent histograms. AB - Single parameter gated flow cytometric fluorescent histograms were obtained on normal donor blood mononuclear cells using several commonly available lymphocyte surface markers. A computer method was developed to average single parameter flow cytometric immunofluorescent histograms. The averaged histograms provide a means of pattern recognition for normal lymphocytes and will aid in the clinical evaluation of lymphocytosis. Averaged histograms may also serve as standards for more advanced analysis. PMID- 3093179 TI - Detection of acid-beta-galactosidase activity in viable human fibroblasts by flow cytometry. AB - The fluorogenic substrate fluorescein-di-beta-D-galactopyranoside was used to detect acid beta-galactosidase in intact cultured human fibroblasts. The accumulation of intracellular fluorescein, as measured by flow cytophotometry was linear with the incubation time in three control strains. The two fibroblast strains from patients with acid beta-galactosidase deficiency did not show an accumulation of intracellular fluorescence. Within one control cell population there was a positive correlation between the amount of accumulated intracellular fluorescein fluorescence and the specific acid beta-galactosidase activity as measured biochemically on sorted cells from different zones of the fluorescence distribution. No correlation was found between the specific acid beta galactosidase activity and the fluorescein fluorescence of three different control cell strains. PMID- 3093180 TI - [Influences of inflammatory macrophages on the proliferation of mouse tumor cells in vitro]. AB - Augmented growth of tumor cells of both syngeneic and allogeneic origin was often observed when these cells were cocultured with the peritoneal inflammatory macrophages of C57BL/6 mouse, induced by thioglycollate in vitro. While large doses of macrophage-activating factor (MAF) were required for activating these inflammatory macrophages to exert the tumoricidal activity, and much less (suboptimal) doses of MAF were required for activating their cytostatic effect on tumor cells. Whether the macrophage inhibits or enhances the tumor cell proliferation, depends not only on the degree of the activation of macrophage, but also on the macrophage/tumor cell ratio. PMID- 3093181 TI - [Calcium-blocking action of nitro compounds on human thrombocytes]. PMID- 3093182 TI - Benzodiazepine antagonist, CGS-8216, in diazepam- or pentobarbital-dependent and non-dependent rats. AB - CGS-8216, a benzodiazepine antagonist, was administered to rats acutely dosed with diazepam, and to rats chronically dosed with diazepam or pentobarbital. The effects of an acute dose of diazepam were antagonized by CGS-8216 but signs of precipitated abstinence were not observed. An apparent arousing effect was seen in non-dependent rats when CGS-8216 was administered after placebo, but no arousal was observed when Ro15-1788 was administered after placebo in non dependent rats. A precipitated abstinence syndrome was elicited with CGS-8216 in rats chronically dosed with diazepam and was very similar to the abstinence syndrome precipitated by Ro15-1788 in diazepam-dependent rats. Like Ro15-1788, CGS-8216 elevated Precipitated Abstinence Scale (PAS) scores in a dose-related manner until a plateau was reached with 5 mg/kg. No signs of precipitated abstinence were observed when CGS-8216 was administered to rats dependent on phenobarbital. PMID- 3093183 TI - [Results of blood gas analysis in newborn lambs with special reference to neonatal respiratory depression]. PMID- 3093184 TI - Correlation of the five test methods to assess chemical toxicity and relation to physical properties. AB - Biological tests using Orizias latipes (LC50 and oxygen uptake test), Moina macrocopa (LC50), and Dugesia japonica (head regeneration test and LC50) were carried out in order to clarify the mutual relationship of these test methods. The oxygen uptake rate of O. latipes was not effective to assess chemical toxicity. Adding the results of the growth inhibition test of Tetrahymena pyriformis (Yoshioka, Y., Ose, Y., and Sato, T. (1985). Sci. Total Environ. 43, 149-157), the correlation coefficients between each two test methods were calculated. The test results except EC50 and LC50 of D. japonica showed a good relation to each other. We determined the solubility and the n-octanol/water partition coefficient (P) of some chemicals used in the test. Log P interpreted the toxicity in mol/liter unit but not in mg/liter. Solubility was not a useful descripter neither in mol/liter nor in mg/liter unit. PMID- 3093185 TI - Comparison of methods to test chemicals for side effects on soil microorganisms. AB - The effects of the test chemicals pentachlorophenol (PCP) and HgCl2 on the bioactivity of microorganisms in three different soils were studied in low and high concentrations (2 and 20 ppm). Bioactivity was measured in long-term experiments (18 weeks) by a threefold application of chemicals to soils of varying moisture content. The selected tests were measurements of ATP, of heat output under aerobic and anaerobic conditions and after amendment with glucose, of soil respiration after the addition of glucose, and Fe(III) reduction. The suitability of each test depends on soil microorganisms, on environmental conditions, and on soil properties. The effects caused by the chemicals were as follows. For the low concentration, stimulation or inhibition were mostly repaired within the observation period. The high concentration mostly induced inhibitions which increased or decreased as a consequence of the repeated application of the chemicals. The effects of chemicals were strongly modified by the soil types: in a soil with high organic matter content, differences to the control were lower than in soils with lower organic matter content. These experiments also indicate that measurement of only one physiological parameter is not sufficient to characterize chemicals ecotoxicologically. PMID- 3093186 TI - [Mediated action of phytogenic antineoplastic agents on rats with Pliss lymphosarcoma]. AB - The action of drugs of plant origin and of alkylating compounds (sarcolysine, prospidin) was accompanied by hormonal changes in rats with inoculated Pliss' lymphosarcoma. After the use of polyphenol plant drugs the secretion of pituitary FSH was inhibited, the blood concentration of testosterone was reduced and the cortisol secretion was substantially increased. The alkylating compounds stimulated the production of FSH, increased the secretion of testosterone, and clearly lowered the cortisol level. PMID- 3093188 TI - Human milk does not degrade TRH. AB - We have found previously that TRH is accumulated in rat milk in biologically active form. TRH was reported to be present in high concentrations in human milk too. These findings together with the absence of TRH degrading activity in plasma of newborns suggest a possible physiological role of the neurohormone coming from milk. We studied, therefore, TRH degrading activity of human milk. TRH incubated in vitro with 100 microliters human milk (4 days and 4 months after delivery) in 0.01 mol l-1 phosphate saline buffer (pH 7.6) with 1% gelatine (total volume 0.3 ml) at 37 degrees C was not degraded during 2 hours as revealed by specific RIA. The addition of the same amount of milk to adult human plasma did not affect intensive TRH degradation. We conclude that human milk does not contain TRH degrading enzymes nor their inhibitors. PMID- 3093187 TI - Biosynthesis, metabolism and role of TRH during the perinatal period (minireview). PMID- 3093189 TI - Epidermal growth factor in human milk and the effects of systemic EGF injection on intestinal calcium transport in suckling rats. AB - Epidermal growth factor (EGF) is a polypeptide that stimulates proliferation and differentiation of a variety of cell types, including intestinal epithelium; it is the agent in human milk that induces mitosis in human fibroblast culture. It has been postulated that EGF in human milk may play an important role in the normal intestinal maturation since specific EGF receptors are present on the surface of intestinal cells. For this reason, human milk samples from mothers delivering prematurely, as well as at term gestation, were analyzed for their content of EGF. Samples from mothers delivering prematurely showed levels of 70 +/- 5 ng ml-1 and those delivering at term had levels of 68 +/- 19 ng ml-1. There was no diurnal variation and no change with length of lactation up to 50 days. Although previous studies demonstrated that subcutaneous injections of EGF given to suckling rats caused changes in morphology and enzyme activities, no studies had demonstrated that EGF caused changes in function. We injected two-week-old suckling rats and three-week-old weanling rats with 0.1 microgram of g-1 BW twice daily for three days. EGF treatment caused a decrease in somatic weight gain, an increase in weight per unit length of bowel, an increase in lactose specific activity and an increase in net calcium transport. In contrast to the two-week old suckling rats, the EGF had no effect on intestinal function although somatic weight gain was also depressed in three-week-old animals. These findings demonstrate that human milk contains substantial amounts of EGF and that systemic injections of EGF can cause both morphological and functional changes in the intestinal tract of suckling rats. PMID- 3093190 TI - Prostaglandins in breast milk. AB - Levels of prostaglandin E2, prostaglandins F2 alpha and prostacyclin (measured as 6-keto PGF1 alpha) were measured by radioimmunoassay in aliquots of foremilk and hindmilk obtained at different stages of lactation, (colostrum, transitional and mature milk), from ten healthy nursing mothers who delivered at term. Immunoreactive prostaglandins E2, F2 alpha and the stable metabolite of prostacyclin 6-keto PGF1 alpha were detected in all fresh human milk samples but not in cow's milk-based formulas. The source of prostaglandins and prostacyclin in breast milk is related to local synthesis of the mammary gland and to the synthesis by the cellular elements of breast milk but not to their level in the maternal circulation. PMID- 3093191 TI - Electrophoretic purification of radioiodinated follicle-stimulating hormone for radioligand receptor assay and radioimmunoassay. AB - A method is described for electrophoretic purification of [125I]human (h) FSH after radioiodination that improves radioligand binding to FSH membrane receptors. Lactoperoxidase-iodinated hFSH was separated from reaction products by electrophoresis on 7.5% polyacrylamide tube gels (PAGE). Material eluted from 3 mm gel slices was analyzed for incorporation of 125I and binding to antibody (RIA) or receptor (RRA), and by sodium dodecyl sulfate-PAGE for protein composition. Sodium dodecyl sulfate-PAGE analysis of individual PAGE fractions demonstrated that iodinated proteins, both higher and lower in apparent mol wt than intact FSH, were separated by PAGE, but not by gel filtration chromatography (Sephadex G-25). PAGE purification of radioligand resulted in significantly greater (compared to gel filtration) RRA sensitivity and specificity. Maximum binding of PAGE-purified [125I]hFSH to excess calf tests membrane receptors was 45%, with a specific activity of approximately 26 microCi/micrograms, as determined by the method of self-displacement. Maximum binding to excess hFSH antisera (NIH anti-hFSH 4) was 80-85%. This allowed a useful final dilution of 1:120,000, thereby facilitating development of a sensitive and specific RIA with this antiserum. These data indicate that PAGE separation of intact [125I]hFSH from other iodinated proteins results in improved radioligand binding, assay sensitivity, and assay specificity. In addition, PAGE-purified lactoperoxidase iodinated hFSH is suitable for use in both RIA and RRA. PMID- 3093192 TI - Ovine prolactin (PRL) and dopamine preferentially inhibit PRL release from the same subpopulation of rat mammotropes. AB - Autoregulation of PRL release was studied at the single cell level by the use of a reverse hemolytic plaque assay. Monodispersed pituitary cells from adult male rats were first preincubated with test substances and then coincubated with antirat PRL antiserum before development of plaques with complement. At the conclusion of the assay, the percentage of all pituitary cells in culture that formed plaques was evaluated microscopically, and the rate of plaque development was used as an index for the rate of hormone release. In controls, the maximal percentage of pituitary cells formed PRL plaques within a 1.5-h antibody incubation period, and addition of TRH (1 X 10(-7) M) did not increase this proportion. Treatment with ovine PRL (oPRL, 100 ng/ml) or dopamine (1 X 10(-7) M), either alone or in combination, caused a comparable suppression of the rate of PRL plaque development, which was reversed by the presence of TRH. Pretreatment of cells with the lysosomotropic agent chloroquine (1 X 10(-5) M) overrode dopamine inhibition of PRL plaque development, but did not influence oPRL inhibition. Taken together, these results demonstrate that oPRL inhibits basal, but not TRH-induced, PRL release from rat pituitary cells and support the view that PRL can act at the pituitary level to inhibit its own secretion. Moreover, the equipotency and lack of additivity exhibited by oPRL and dopamine coupled with the differential effects of chloroquine suggest that these factors both act upon the same subpopulation of mammotropes to inhibit PRL release, but by separate intracellular mechanisms. PMID- 3093193 TI - Desensitization to gonadotropin-releasing hormone in perifused chicken anterior pituitary cells. AB - A perifusion method consisting of dispersed chicken anterior pituitary cells suspended in columns of Bio-Gel was developed to monitor the dynamics of LH release. The perifused cells responded to chicken I GnRH (Gln8-GnRH) in a dose dependent manner. The ED50 was 3 X 10(-10) M, and maximal LH release occurred in response to 4 X 10(-9) M Gln8-GnRH. Continuous administration of 10(-7) M Gln8 GnRH and agonist stimulated an initial 8- to 10-fold increase in LH release within minutes. LH release then declined rapidly, reaching basal levels within 100 min. A biphasic response was noted. Calcium ionophore A23187 was effective in releasing additional LH from cells desensitized to 10(-7) Gln8-GnRH and agonist, indicating that total cellular LH was not depleted. In contrast, delivery of 2 min pulses of 10(-7) M and 10(-9) M Gln8-GnRH at a frequency of one pulse every 30 or 60 min for 3-5 h maintained pituitary responsiveness. Exposure to 10(-7) M Gln8-GnRH for 20 min was sufficient to desensitize pituitary cells to subsequent Gln8-GnRH stimulation. However, 20-min exposure to 10(-7) M GnRH antagonist neither evoked LH release nor had a desensitizing effect on subsequent stimulation by 10(-7) M Gln8-GnRH, indicating that receptor activation, not merely receptor binding, is necessary for Gln8-GnRH-mediated homologous desensitization. Pituitary cells desensitized by 20-min exposure to 10(-8) M Gln8 GnRH maintained responsiveness to a higher dose (10(-6 M) of Gln8-GnRH, suggesting that down-regulation of pituitary GnRH receptors might play a part in desensitization. Calcium ionophore A23187 partially desensitized pituitary cells to subsequent stimulation with Gln8-GnRH, probably due to depletion of releasable LH or desensitization of calcium-coupled secretory mechanisms. In calcium-free medium, 10(-7) M Gln8-GnRH did not evoke LH release, but nevertheless partially desensitized cells to subsequent 10(-7) M Gln8-GnRH stimulation. Thus desensitization is partially calcium-dependent. These findings demonstrate that the GnRH-mediated desensitization of gonadotrophs is a characteristic of chicken pituitary cells as in the mammal. However, chicken pituitary cells differ from mammalian cells in that desensitization is more rapid and partially dependent on extracellular calcium. PMID- 3093194 TI - Plasma protein(s) yields met-enkephalin-related peptides in near-micromolar concentrations when treated with pepsin. AB - Treatment of animal and human plasmas with pepsin yielded large quantities of immunoreactive methionine5-enkephalin (i-met-ENK). The concentrations measured after pepsin treatment were 0.1-0.5 microM, about 1000 times the normal circulating level of i-met-ENK (0.03-0.3 nM). The reaction was shown to be time and pH dependent and to involve the action of pepsin on a protein(s) of about 65,000 mol wt. Pepsin-generated i-met-ENK from rat plasma gave three major peaks during reverse phase HPLC, one of which (approximately 25% of the total) coeluted with methionine5-enkephalin sulfoxide and also completed in a radioreceptor assay for opiate-related substances. In addition, this material produced met-ENK-like effects on vascular permeability in rat skin and inhibited electrically induced contractions of the isolated guinea pig ileum in a naloxone-sensitive manner. The plasma substrate(s) that yielded i-met-ENK was distinguished from adrenal proenkephalins, since partially purified plasma substrate(s) did not liberate i met-ENK upon digestion with trypsin and carboxypeptidase B. Although it is possible that these peptides differ from met-ENK in amino acid sequence, the results presented here suggest that met-ENK-related substances might be formed physiologically by the action of a pepsin-related processing enzyme(s) on plasma substrate(s). Such a mechanism would be analogous to that used in the renin angiotensin system. PMID- 3093195 TI - Identification and regulation of tissue plasminogen activator activity in rat cumulus-oocyte complexes. AB - Plasminogen activators convert plasminogen into plasmin, a serine protease that initiates extracellular proteolysis. Two types of plasminogen activator activities have recently been demonstrated in granulosa cells, and the proteolysis-inducing enzymes are believed to be involved in ovulation. However, little attention has been paid to the presence of these enzymes in oocytes. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by a fibrin overlay technique, we studied plasminogen activator activity in oocytes. Denuded oocytes collected from ovaries of hypophysectomized, estrogen-treated immature rats contained a tissue-type plasminogen activator (tPA), but not urokinase (uPA). In contrast, oocyte-free granulosa cells in these preantral follicles contained uPA, but not tPA. The tPA activity found in oocytes was plasminogen dependent; incubation with increasing numbers (25-200) of denuded oocytes resulted in a dose-dependent increase in fibrinolysis only in the presence of plasminogen. Cellular localization of tPA was studied in the preantral follicles using an immuno-cytochemical method. Positive tPA staining was detected in the cytoplasm, but not in the germinal vesicle or zona pellucida of the oocytes. Furthermore, analysis using a reverse fibrin-overlay method did not reveal the presence of a plasminogen activator inhibitor. Culturing of denuded oocytes for 24 h increased the cellular content of tPA, but the enzyme activity was not further enhanced by treatment with FSH or forskolin. Also, no tPA activity was detected in the medium. We further studied plasminogen activator activities in the cumulus-oocyte complexes. Although only tPA activity was detected in freshly obtained cumulus-oocyte complexes, incubation for 24 h increased both tPA and uPA activity. Furthermore, tPA, but not uPA, activity was stimulated by treatment with FSH or forskolin. This was accompanied by the secretion of tPA into the medium. The identity of tPA and uPA in the cumulus-oocyte complexes was further confirmed by immunoprecipitation with specific antibodies. Isolation of denuded oocytes and cumulus cells after hormonal stimulation of the cumulus-oocyte complexes suggested that tPA activity was stimulated in both cell types and that the cumulus cells may mediate the action of FSH and forskolin on oocytes. In conclusion, the detection and regulation of tPA activity in cumulus-oocyte complexes suggest possible involvement of this enzyme in ovulation or the process of cumulus cell expansion and dispersion. Changes in oocyte tPA content may also serve as an indicator of oocyte development. PMID- 3093196 TI - Intrafollicular distribution of plasminogen activators and their hormonal regulation in vitro. AB - Recent studies from our laboratory corroborated the suggested role of plasminogen activation in follicular rupture at ovulation, and its involvement in the activation process of collagenolysis in the follicle. In the present study, the molecular types and cellular source of plasminogen activator (PA) were examined. Explanted preovulatory follicles produced in vitro both urokinase type and tissue type (t-PA) activators. Upon gonadotropin stimulation a highly significant increase in t-PA, but not in urokinase type, was observed. Separation of the follicle into granulosa cells and residual tissue, mainly theca, revealed that both compartments produce both types of PA. The granulosa compartment was found to produce 80-90% of the total follicular PA activity. Gonadotropins stimulated predominantly t-PA. Most of the gonadotropin-enhanced PA activity produced by granulosa cells was secreted into the culture medium, whereas that from thecal origin remained in the tissue. Likewise, in whole follicles only about 10% of PA was secreted into the medium. Gonadotropin-induced PA activity in vitro was reduced by inhibitors of steroidogenesis. This inhibition was overcome by the addition of estradiol-17 beta. The inhibition of steroidogenesis affected predominantly the t-PA type of PA. In conclusion, the granulosa cells contribute most of the follicular PA activity, and t-PA is predominantly enhanced by gonadotropin and estrogen. It seems, therefore, that t-PA is the activator involved in the processes leading to follicular rupture. PMID- 3093197 TI - Presence of estradiol-binding proteins in gastrointestinal tract of male rats. AB - In the cytosol from pancreas, fundus, and antrum of rats, two classes of specific, estradiol (E2)-binding proteins (EBPs) were observed, with 5- to 10 fold differences in their binding affinities, and 10- to 20-fold differences in their binding capacities. EBPs, both type I [high affinity, dissociation constant (Kd) less than 1.0 nM] and type II (low affinity, Kd greater than 5 nM), in the fundus were found to be specific for estrogens. None of the corticoids, or androgenic and progestogenic steroids tested demonstrated any significant inhibition of binding of radiolabeled E2 to EBP at doses as high as 5 X 10(-6) to 5 X 10(-5) M. At high concentrations of E2 (greater than 2-5 nM), nonsaturable EBPs were additionally observed in the pancreatic cytosol. In the intestine, however, EBP was not detected at E2 concentrations of less than 2 5 nM. Similarly, progesterone-binding proteins were nonmeasurable in either pancreas or gastrointestinal tissues at less than 5 nM concentrations of the ligand, indicating questionable physiological significance of the latter binding sites. The two classes of EBPs in the pancreas and stomach of rats, measured at near physiological E2 concentrations of less than 2 nM, however, may play a significant role in gastric and pancreatic functions, since sex steroids have been documented to have specific effects on structure and function of pancreas and stomach. PMID- 3093198 TI - Testicular control of prostaglandin E2 production in rat vas deferens. AB - Orchidectomy decreased and testosterone (T) replacement restored prostaglandin E2 (PGE2) concentrations in adult rat vas deferens. To explain this finding, phospholipase A (PLase-A) and PG synthetic activity were studied in vas tissue from 9-week-old rats orchidectomized with or without T replacement as well as in rats in which the cauda epididymidis was ligated. PG synthetic activity fell to 3% of intact levels in 14-day castrate rats and was restored to normal by T replacement. Although vas PLase-A activity was also significantly (P less than 0.01) reduced to 38% of the control level in 14-day castrate rats, this change appears in part to reflect a castration-related increase in endogenous phospholipid concentrations. Further, T replacement only partially restored PLase A activity to 59% of intact levels. Ligation of the cauda epididymidis in intact rats reduced vas PLase-A activity to castrate levels without altering vas T concentration. These results demonstrate both a direct effect of T on the biosynthesis of PGs in rat vas deferens as well as a paracrine effect, which appears to be mediated by a factor(s) other than T. These data suggest the existence of a new mechanism through which testicular products contribute to the function of the vas deferens. PMID- 3093199 TI - Monoamine oxidase in rat ovary during the estrous cycle. A histochemical study by a new coupled peroxidatic oxidation method. AB - A new coupled peroxidatic oxidation method for histochemical detection of monoamine oxidase (MAO) was applied to rat ovary. With this new method, fixed tissues could be used, and two forms of MAO could be identified by use of selective inhibitors. MAO activity was observed in the corpora lutea, interstitial gland cells, and blood vessels. In the corpora lutea, no activity was detected during the first estrous cycle, but strong activity was observed in the next two cycles. MAO in blood vessels showed characteristic changes of activity during the estrous cycle. The results suggest that MAO activity might possibly be involved in ovulation and progesterone metabolism in the ovary. Like other organs, rat ovary was found to contain two types of MAO; type A MAO was predominant in the corpora lutea. On the other hand, only one type of MAO, type B, was found in the blood vessels. PMID- 3093200 TI - Brain temperature in the rat midbrain reticular formation is regulated by bombesin and TRH. AB - We investigated the effects of intraventricular (ivt) injection of bombesin on the TRH-induced increase in temperature in the midbrain reticular formation (mrf) of the rat brain under pentobarbital anesthesia. Ivt injection of TRH in a dose of 3 nmol significantly antagonized the decrease in brain temperature induced by pentobarbital, and this antagonistic action of TRH was dose-related. Ivt injection of 3-300 pmol bombesin produced a dose-related decrease in brain temperature in response to 3 nmol TRH injection. The present data provide evidence that bombesin and TRH produce opposite actions on thermoregulation of the mrf in the rat. PMID- 3093202 TI - Long-term bromocriptine therapy and predictive tests in acromegaly. AB - The value of predictive tests in bromocriptine therapy and the effects of long term bromocriptine therapy were investigated in acromegalic patients. In 72 acromegalic patients, there was a tendency for patients with a plasma GH response to TRH or with an elevated basal plasma PRL level, but without a plasma GH response to LHRH, to have a plasma GH response to bromocriptine, though statistical analysis did not reveal a significant difference. Acute and chronic effects of bromocriptine were significantly interrelated, while the chronic effect of bromocriptine and abnormal plasma GH response to TRH or elevated plasma PRL levels were not, in 18 acromegalic patients. These results suggest that the acute bromocriptine test is a better predictor than the TRH test and plasma PRL levels for evaluating the effects of chronic bromocriptine therapy. To maintain the low plasma GH levels, increasing doses of bromocriptine were needed in most patients, and failure to control the elevated GH level despite increasing doses was observed in 2 of 18 patients. PMID- 3093201 TI - Antagonistic interactions of transforming growth factors in the regulation of granulosa cell differentiation. AB - The role of transforming growth factors (TGFs) in the acquisition of granulosa cell aromatase activity was investigated in vitro in a primary culture of granulosa cells harvested from immature, diethylstilbestrol-treated rats. Basal aromatase activity, as assessed by the generation of radioimmunoassayable estrogen, was negligible, remaining unaffected by treatment with either TGF alpha or TGF beta applied by themselves at the 10 ng/ml dose level. Whereas treatment with FSH produced a substantial increase in the extent of aromatization, concurrent treatment with TGF beta (0.01-10 ng/ml) resulted in dose-dependent augmentation of the FSH effect with an apparent median effective dose of 224 +/- (SE) 32 pg/ml (ca. 9 pM), and a maximal effect 3.6-fold greater than that induced by FSH alone. In contrast, concomitant treatment with TGF alpha (0.01-10 ng/ml) resulted in dose-dependent attenuation of FSH action with an apparent median inhibitory dose of 330 +/- (SE) 40 pg/ml (ca. 60 pM), and a maximal inhibitory effect of 91 +/- (SE) 2%. However, combined treatment with identical (10 ng/ml) maximally effective doses of both TGFs had little or no effect on the FSH stimulated accumulation of estrogen, suggesting mutual neutralization by the opposing actions of these peptides. Further evaluation of the antagonistic interaction of the TGFs revealed it to be dose-dependent in that maximally effective doses of TGF alpha (10 ng/ml) partially overcame the stimulation of aromatase activity brought about by relatively low (less than 0.3 ng/ml) but not higher (greater than 1 ng/ml) concentrations of TGF beta, thereby shifting the TGF beta dose-response curve to the right. Treatment with either TGF had no significant effect on granulosa cell DNA content or synthesis, plating efficiency or viability. Taken together, these findings suggest that picomolar concentrations of exogenously provided TGF alpha TGF beta exert potent but diametrically opposed effects on the acquisition of granulosa cell aromatase activity and that the interaction between these two peptides is antagonistic in nature. Our findings further suggest that these direct cytodifferentiative effects of the TGFs may represent intrinsic novel properties of these peptides distinct from their well-established role in the regulation of cellular growth. PMID- 3093203 TI - Impaired steroidogenic function of corpora lutea from hyperprolactinemic baboons induced by sulpiride. AB - It has been noticed that hyperprolactinemia can cause luteal insufficiency as well as anovulation in women. In order to explore the mechanism underlying this disorder, hyperprolactinemia was induced in baboons (Papio cynocephalus) by daily administration of sulpiride during follicular and early luteal phases. In hyperprolactinemic baboons, the plasma progesterone level was suppressed without notable changes in plasma estradiol, LH and FSH levels. When corpora lutea from these baboons were examined in vitro to investigate their ability to convert 14C pregnenolone into various steroids, there was progressive inhibition of steroid metabolism related to the plasma levels of prolactin. These findings strongly suggest, although do not actually prove, that an elevated level of prolactin could directly impair luteal function by adversely affecting 3 beta hydroxysteroid dehydrogenase activity. PMID- 3093204 TI - Rat ovarian and adrenal prolactin receptors. Sizes and effects of divalent metal ions. AB - Receptor fractions were prepared from follicle-rich ovaries (for FSH), luteal cell-rich ovaries (for LH and PRL), and adrenals (for PRL) of rats. Divalent metal ions, Mg++, Ca++, and Mn++ showed inhibitory effects on the binding of LH and FSH to their receptors. The binding of the former was more sensitive to these ions than the latter. On the other hand they showed bell-shaped promotive effects on PRL-ovarian receptor binding, the maximal effects being observed at 10-20 mM. Besides these ions, Ba++ also had a promotive effect, while other divalent metal ions such as Zn++, Cd++, Ni++, and Co++ showed inhibitory effects on PRL-ovarian receptor binding at 5 mM. Mg++ and Ca++ also promoted PRL-adrenal receptor binding, while Mn++ promoted the binding at 10 mM but inhibited it at higher concentrations. Association constant (Ka) and binding capacity (Bmax) of PRL receptors of the ovary and the adrenal were significantly different (ovary: Ka = 0.69 X 10(10) M-1, Bmax = 62 fmol/mg protein, adrenal: Ka = 0.21 X 10(10) M-1, Bmax = 99 fmol/mg protein). Ka of the ovarian PRL receptor was not influenced by these divalent ions, while that of the adrenal receptor was doubled by Ca and Mn ions, Bmax of the latter was also increased. A cooperative effect of Mg and Ca ions was observed on Ka and Bmax of the adrenal receptor. The sizes of the PRL binding sites of these organs revealed by affinity labelling were 17K and 40K in the ovary, and 40K and 110K in the adrenal. These results indicate the different properties of receptors in these different target organs. PMID- 3093205 TI - Inhibition of the binding of R-5020 and rat uterine progesterone receptors by long chain fatty acids. AB - Long chain fatty acids were known to interfere with the binding between rat uterine estrogen receptors and estradiol. The effect of long chain fatty acids on the binding between rat progesterone receptors and 3H-R5020 was studied. The binding was inhibited by palmitic acid, palmitooleic acid, arachidonic acid and docosahexaenoic acid. Docosahexaenoic acid was the strongest inhibitor and palmitic acid was the weakest inhibitor. The inhibitory effect of palmitic acid and arachidonic acid was dose dependent. In rat uterine cytosols, there existed an arachidonic acid binding factor which was distinct from progesterone receptor. The inhibitory mechanisms of long chain fatty acids was not clear, but the inhibitory effect was stronger if the number of carbon atoms increased with the number of double bonds. PMID- 3093206 TI - Activated lymphocytes in patients with newly diagnosed type 1 (insulin-dependent) diabetes mellitus. AB - The expression of activation antigens (transferrin receptor, IL-2 receptor and Ia antigen) on circulating T lymphocytes from Japanese children with Type 1 diabetes was studied using five monoclonal antibodies (Ab), OKT9, anti-Tac Ab, OKIa1, anti human HLA-DR Ab and OKT3. For detecting Ia positive T cells, the dual staining technique using OKT3 and anti-Ia antibody was employed. Four out of six patients (67%) with newly diagnosed Type 1 diabetes showed a raised level of either OKT9 or Tac positive cells when examined at diagnosis. These patients, however, rapidly lost these activation antigens after the insulin therapy was started. In contrast, in 32 long-standing patients, only 2 (6%) had a high percentage of OKT9 positive cells and none of them demonstrated Tac positive cells. One out of six newly diagnosed patients or three out of 21 long-standing patients had a significantly high percentage of Ia-positive T cells compared with normal subjects. In poorly controlled long-standing patients whose HbA1 value was higher than 14%, none of them had an increased number of activated lymphocytes. Therefore, it is unlikely that insulin deficiency and hyperglycemia were responsible for the changes observed in these studies. Activated lymphocytes might be related to activation of the immune system involved in pathogenesis of Type 1 diabetes. PMID- 3093207 TI - Chemical characterization of high buoyant density proteoglycan accumulated in the affected skin of pretibial myxedema of Graves' disease. AB - From three patients with pretibial myxedema (PTM) of Graves' disease, a portion of the skin involved was biopsied, analyzed for proteoglycans and the results were compared with those obtained with euthyroid and hyperthyroid subjects without PTM. The tissue specimen was extracted with 4 M guanidine HCl and subjected to subsequent CsCl density gradient centrifugation. Glycosaminoglycan and protein were recovered in the heaviest density fraction in the three specimens obtained from patients with PTM and not from subjects without PTM. From the analysis by Sepharose CL-6B column, glycosaminoglycan was present as a form of proteoglycan because alkaline borohydride treatment released single chain glycosaminoglycan with a molecular weight of 77,000 or 66,000. The digestion with chondroitin ABC lyase revealed that the majority of proteoglycan in the skin tissue was chondroitin sulfate or dermatan sulfate, and heparan sulfate comprised the minor component (14-34%). The rate of proteoglycan biosynthesis was examined by 35S incorporation into glycosaminoglycan's by cultured fibroblasts from PTM and normal skin. Incorporation of 35S into both proteoglycan and single chain glycosaminoglycan was observed in the fibroblasts of PTM patients as well as of those of subjects without PTM, although the rate of synthesis was more pronounced in the former. The rate of synthesis was influenced neither by normal serum or serum from a pretibial myxedema patient. Since proteoglycan accumulation was detected only in the affected skin of PTM patients, the impairment of local degradation and the proteoglycan clearance mechanism may also be involved. PMID- 3093208 TI - Antiepileptic effects of a calcium antagonist (nimodipine) on cefazolin-induced epileptogenic foci in rabbits. AB - The epileptogenic properties of cefazolin (CFZ) were utilized to induce an electrophysiological pattern of epilepsy in the rabbit. CFZ, cortically applied in different concentrations (2 or 4%), produced epileptic activity in a degree proportional to the concentration of the substance. In this experimental epilepsy model, we evaluated the effects of increasing doses (0.025, 0.05, and 0.1 mg/kg i.v.) of the calcium antagonist nimodipine (Bay e 9736). In the evaluation of nimodipine effects, the spike-and-wave burst frequency per minute was taken into account. These data were compared with those of placebo-treated (Bay e 9736 control test) control groups and statistically evaluated by two-tailed t test. In 2% CFZ-induced epilepsy, nimodipine at the 0.025- and 0.05-mg/kg doses did not produce significant changes in the EEG pattern. A statistically significant reduction (p less than 0.001) in epileptic activity was observed at the 0.1-mg/kg nimodipine dose. This reduction was seen first in the contralateral focus leads and persisted for the entire time of observation. In the more intense epileptic form (4% CFZ), nimodipine at the doses employed did not induce noteworthy EEG modifications. These data indicate that nimodipine exerts an antiepileptic effect. The possible mechanisms involved in this activity of a calcium antagonist are discussed. PMID- 3093209 TI - Correlation between effects of acute acetazolamide administration to mice on electroshock seizure threshold and maximal electroshock seizure pattern, and on carbonic anhydrase activity in subcellular fractions of brain. AB - The relationships between inhibition of carbonic anhydrase (CA) activity in cytoplasmic, microsomal, and myelin subcellular fractions obtained from cerebral cortex, subcortex, and cerebellum and electroshock seizure threshold (EST) and modification of the extension/flexion (E/F) ratio following maximal electroshock seizures (MES) were ascertained in Swiss-Webster mice given 40 and 200 mg/kg acetazolamide. The parameters were determined at 1, 4, and 24 h after administration of acetazolamide. The results showed that changes in the E/F ratio induced by acetazolamide correlated linearly (r = 0.90) with changes in CA activity in the cytoplasm of the subcortex. However, there was an inverse power function correlation (r = 0.92) between EST and CA activity in the myelin fraction of the cerebral cortex. The time course of acetazolamide inhibition of CA activity in these two fractions also paralleled the time course of its effects on EST and E/F ratio. Thus, acetazolamide decreases susceptibility to seizures (raises EST) by inhibiting myelin CA and prevents spread of seizure activity by inhibiting CA in the cytoplasm of glial cells. The CO2 that accumulates as a result of CA inhibition in these two fractions causes profound changes in brain function. PMID- 3093210 TI - Induction of new carbonic anhydrase II following treatment with acetazolamide in DBA and C57 mice. AB - The mechanism by which animals develop tolerance to the antiepileptic effects of the carbonic anhydrase (CA) inhibitor, acetazolamide, was explored using a quantitative immunocytochemical method. Cerebral cortex sections of DBA/2J mice susceptible to audiogenic seizures and of C57BL/6J nonsusceptible mice were stained with antibody to mouse CA II in controls and following treatment with acetazolamide (40 and 200 mg/kg) for 1, 3, and 5 days. The percentage increases in CA II fluorescent intensity of cells from C57 mice treated with 40 and 200 mg/kg acetazolamide over those of untreated mice were 22 and 36%, respectively, after 1 day, 32 and 40%, respectively, after 3 days, and 17 and 40%, respectively, after 5 days of treatment. The corresponding percentage increases in fluorescent intensity of cells from DBA mice over controls were 13 and 32%, respectively, after 1 day, 17 and 41%, respectively, after 3 days, and 26 and 58%, respectively, after 5 days of treatment. The fluorescent intensity of cells from untreated DBA mice was 35% greater than those of untreated C57 mice. In C57 mice the maximum amount of CA II per cell at each dose occurred 24 h after acetazolamide treatment, whereas the amount in DBA mice continued to increase with time and dose up to 5 days. The differences between the two strains can be explained by changes in distribution of CA II to subcellular locations or by defects in phosphorylation of the molecule. PMID- 3093211 TI - Visual evoked potentials, brainstem auditory evoked potentials, and quantitative EEG in Baltic progressive myoclonus epilepsy. AB - Visual and brainstem auditory evoked potentials (VEP and BAEP, respectively) and quantitative EEG were studied in 16 patients with Baltic progressive myoclonus epilepsy (PME). The study demonstrated significantly delayed VEP latencies but normal amplitudes in Baltic PME. BAEPs showed slight but significant prolongation in central conduction time. Quantitative EEG revealed diminution of beta and alpha activity and accentuation of theta and delta activity. The slowing in VEP latencies is suggested to be due to impaired synaptic transmission and to reflect dopaminergic dysfunction in Baltic PME. We conclude that there is a multimodal disturbance in sensory projections to cortical areas in Baltic PME. The results give further evidence that nondemyelinating disorders--but with synaptic transmission defects--can produce changes in evoked potentials. The changes in epileptic brain are not confined to hyperexcitable epileptic neurons, but more widespread electrophysiological phenomena are produced. PMID- 3093212 TI - Sodium valproate and valpromide: differential interactions with carbamazepine in epileptic patients. AB - To evaluate the comparative effects of valproic acid (VPA) and valpromide (VPM) on plasma levels and protein binding of carbamazepine (CBZ) and CBZ-10,11-epoxide (CBZ-E), 12 adult epileptic patients stabilized on CBZ monotherapy were divided into two groups. One group (n = 6) received sodium valproate (1,100 mg/day) for 2 weeks, while the other group (n = 6) was given, for the same period, a dosage of VPM (1,200 mg/day) expected to produce VPA levels equivalent to those achieved with valproate. Plasma CBZ levels were not affected by either treatment. In the valproate-treated group, plasma CBZ-E levels increased by 101% (range, 29-238%) within 1 week of combined therapy (p less than 0.02) and returned to baseline values after VPA treatment was stopped. In the VPM-treated patients, the elevation of plasma CBZ-E levels was much greater. In this group, plasma CBZ-E increased by 330% (range, 110-864%), and this was associated in two patients with the appearance of adverse effects which subsided after reducing the VPM dosage. The plasma protein binding of CBZ and CBZ-E was not affected significantly by VPM or valproate therapy. Plasma VPA levels were similar in the two groups. It is concluded that VPM is not simply a prodrug of VPA. Although both VPA and VPM increase CBZ-E levels--probably by inhibiting the enzyme epoxide hydrolase--the interaction caused by VPM is of much greater magnitude and potential clinical significance. PMID- 3093213 TI - Serum carnitine during valproic acid therapy. AB - This study was initiated to examine the influence of valproic acid (VPA) on serum carnitine, as well as the possible etiological role of carnitine in VPA-induced fatal hepatotoxicity. Free, total, and short-chain acylcarnitine were measured in the serum of 21 pediatric patients receiving VPA therapy, 21 healthy matched controls, and 21 patients receiving various antiepileptic drugs other than VPA. The free carnitine level was lowest in the VPA group (p less than 0.05), and the short-chain acylcarnitine/free carnitine ratio was highest in the VPA group (p less than 0.01). Patients receiving VPA polytherapy had lower total carnitine values than patients receiving VPA monotherapy (p less than 0.05). No correlation was found between serum ammonia and VPA drug levels. A 3 1/2-year-old girl developed hepatic failure under VPA therapy. Her serum carnitine values were normal. Despite the oral intake of L-carnitine this patient died. In this case, apparently VPA-induced hepatotoxicity was not associated with carnitine deficiency. The reduction of carnitine in the serum of VPA-treated patients is most probably due to alterations of fatty acid metabolism. However, neither primary carnitine deficiency nor VPA-induced secondary carnitine deficiency can be the only reason for the VPA-induced fatal hepatotoxicity. PMID- 3093214 TI - Double-blind withdrawal of phenytoin and carbamazepine in patients treated with progabide for partial seizures. AB - Of 30 patients who completed a study of progabide (PGB) as an add-on to both phenytoin (PHT) and carbamazepine (CBZ), 11 volunteered for a double-blind withdrawal protocol in which the PHT and CBZ were to be withdrawn. All patients were receiving 24-32 mg/kg/day PGB in combination with PHT and CBZ. Each patient was randomly assigned to withdrawal of either CBZ or PHT in the first block, and then withdrawal from the other in the second block in an attempt to achieve PGB monotherapy. Seizure occurrence was monitored by sequential analysis, and if a significant increase over baseline seizure frequency occurred, the dose of PGB was increased to a maximum of 45 mg/kg/day. If seizure frequency remained above baseline, the drug being withdrawn was added back and an attempt made to withdraw the other. The study was terminated if these adjustments were not successful in decreasing seizure frequency to baseline. At the conclusion of the study, three patients were being treated with PGB and PHT, two with CBZ and PGB, and six with all three. This study demonstrated the applicability of sequential analysis to antiepileptic drug trials. PMID- 3093216 TI - Gas chromatographic and mass spectrometric analysis of polychlorinated biphenyls in human placenta and cord blood. AB - Gas chromatographic and mass spectrometric analyses of polychlorinated biphenyls (PCBs) in placenta, maternal blood, cord blood, and milk were carried out. Trichlorobiphenyl, tetrachlorobiphenyl, pentachlorobiphenyls, and hexachlorobiphenyls were identified by the mass chromatogram and the mass spectra. Some minor peaks of PCBs were identified by gas chromatography. The relationship between the PCB concentration in placenta and that in milk is different in each PCB congener. The higher the chlorine content of the PCB congener, the more significant the correlation. No significant but a low negative correlation exists between the concentration of some PCB congeners in the placenta and that in cord blood. On the other hand, a significant linear correlation exists between the concentration of hexachlorobenzene in the placenta and that in cord blood. The transplacental transport of each PCB congener varied depending upon its chemical nature. Trichlorobiphenyl and tetrachlorobiphenyl were more transferable than hexachlorobiphenyls. The results show that the placenta and cord blood are useful human samples to analyze the body burden of environmental pollutants and to estimate their transfer from mother to fetus. PMID- 3093215 TI - The prognosis of photosensitivity. AB - Since 1968, annual EEG recordings during photic stimulation using a standardised technique have been made on photosensitive patients and siblings. In 1983, 72 were aged greater than or equal to 20 years and 14 were aged 16-19 years. Mean duration of follow-up was 9.8 +/- 4.8 years. Seventy-five patients were treated with sodium valproate (VPA), which was withdrawn in 15 but restarted in eight because of return of photosensitivity. Eighty-two patients had seizures at some time; at follow-up 58 were receiving monotherapy with VPA, seven were receiving comedication, and three were taking other drugs. Fifty-four of them were seizure free, as were 10 of the 15 who were not being treated with drugs. Photosensitivity disappeared in 44 of 65 patients at a mean dosage of VPA at 21.5 +/- 6 mg/kg day. In 55 of 86 patients photosensitivity was no longer present at follow-up; in 18, slight abnormality was evoked by intermittent photic stimulation, and in 13, photoconvulsive responses were still present. Eighteen patients were not receiving drugs, 10 of them being no longer photosensitive at the mean age of 24.5 +/- 4.9 years. Thirty-one treated and untreated patients were still photosensitive at age 21.5 +/- 3.4 years. Photosensitivity disappeared earlier in those treated with VPA than in the untreated. Spontaneous remission in the treated cases may have occurred at 22.9 +/- 2.5 years of age. Photosensitivity appears around puberty and may disappear around 24 years of age. Photosensitive epilepsy is easily and rapidly controlled by VPA. PMID- 3093217 TI - Health effects of low-level exposure to polychlorinated biphenyls. AB - A polychlorinated biphenyl (PCB) spill resulting from a transformer explosion in Syracuse, New York, with no subsequent fire, provided an opportunity for the examination of the effects of low-level PCB exposure without the confounding presence of furans and dioxins. The incident provided 52 individuals exposed to PCB among building personnel, police, firemen, and public utility employees. Sixty-eight nonexposed were matched to the exposed group by sex, age, employer, and job description. Data were collected on the exposed relative to their activities at the spill site, their location, possible routes of exposure, duration of exposure, and subsequent health effects. Exposed and nonexposed were interviewed for past medical history and relevant symptoms. Blood chemistries were studied inclusive of SGOT, SGPT, total protein, CBC, cholesterol, and triglyceride levels, as well as a fasting blood PCB level measurement. Six weeks after the spill, exposed and nonexposed were reinterviewed and had their blood work repeated except for the CBC and PCB levels. Exposed and nonexposed laboratory results were unremarkable. Some transient skin irritation believed to be associated with PCBs was noted. There were significant PCBs in blood level trends for occupation, age, duration of exposure, and level of alcohol consumption. Triglyceride level was highly correlated with PCB level. This relationship held when age and alcohol consumption were controlled for. PMID- 3093218 TI - The effect of SO2 on the clearance of Listeria monocytogenes from the lungs of emphysematous hamsters. AB - The effect of sulphur dioxide on the clearance of Listeria monocytogenes from normal and emphysematous hamsters was assessed by measuring the number of colony forming units recovered from whole lung homogenates. Continuous exposure to SO2 after intratracheal instillation of Listeria significantly altered the clearance of viable bacteria from the lungs of emphysematous but not normal hamsters. Preexposure of hamsters to SO2 for 2 weeks prior to respiratory infection had similar effects. The emphysematous hamsters exposed to SO2 had a lower average number of Listeria in the lungs after the first week of infection than control groups. This effect appears to result from the combined influence of the SO2, the Listeria infection, and the emphysematous condition within the lungs. PMID- 3093219 TI - Mutagenicity studies with safrotin in Drosophila melanogaster and mice. AB - The mutagenicity of Safrotin [(E)-0-2-isopropoxy carbonyl-1-methyl vinyl O-methyl ethyl phosphoramidothioate] an organophosphorus insecticide was analyzed in Drosophila melanogaster and mice. Sex-linked recessive lethals and II-III translocations were scored in Drosophila while in mice as per in vivo test methods micronucleus test chromosomal aberrations and a sperm morphology assay were made. Different concentrations of the chemical were administered to D. melanogaster by adult and larval feeding and to mice by oral intubation. In the Drosophila test system the investigation yielded negative results revealing the nonmutagenic activity of the insecticide while a weak mutagenic activity was noticed in the mouse test system. PMID- 3093220 TI - Enterococci and antifolate antibiotics. PMID- 3093221 TI - Treatment of uncomplicated urogenital gonorrhoea in women with a single dose of enoxacin. AB - One hundred and twenty-three female patients suffering from uncomplicated urogenital gonorrhoea were treated in a double blind randomised trial with either 200 mg enoxacin (one capsule of 200 mg, one of placebo) or 400 mg enoxacin (two capsules of 200 mg). The cure rate in the 46 evaluable patients in the 400 mg group was 100%, and in the 40 evaluable patients in the 200 mg group 98.7%. Minor side effects such as nausea, headache and skin rash occurred in three of 109 evaluable patients (2.8%). The minimum inhibitory concentration of enoxacin for the Neisseria gonorrhoeae strains isolated varied between 0.03 and 0.12 mcg/ml. Enoxacin would seem to be a very effective drug in the treatment of uncomplicated urogenital gonorrhoea in female patients. PMID- 3093222 TI - Emergence of beta-lactamase producing anaerobic bacteria in the tonsils during penicillin treatment. AB - The emergence of beta-lactamase producing bacteria in the microflora in the oropharyngeal cavity was studied in ten healthy volunteers treated with 1 g phenoxymethylpenicillin b.i.d. for ten days. Beta-lactamase activity in saliva was also investigated. A significant increase in the number of beta-lactamase producing strains of Bacteroides species and Fusobacterium nucleatum was observed. One beta-lactamase producing Staphylococcus aureus strain was recovered in one of the volunteers before the penicillin administration started and three Staphylococcus aureus strains produced beta-lactamase after ten days of antibiotic treatment. Beta-lactamase-production in Haemophilus influenzae, Haemophilus parainfluenzae or Branhamella catarrhalis was not observed before, during or after the antibiotic treatment. Beta-lactamase activity was noted in the broth cultures from one volunteer colonized with a beta-lactamase producing Escherichia coli strain. Beta-lactamase activity in saliva was observed in all volunteers, the activity increasing significantly in parallel to the increase of beta-lactamase producing bacterial strains. Beta-lactamase activity in saliva was completely inhibited in vitro by clavulanic acid and p-chloromercurbenzoate and about 70-80 per cent of the activity was inhibited by cefoxitin. The increase of beta-lactamase producing bacteria in the oropharynx as a consequence of penicillin treatment raises doubt as to whether penicillin is the drug of choice in the treatment of tonsillitis caused by group A streptococci when previous treatment has failed. PMID- 3093224 TI - Etiology of community-acquired pneumonia in out-patients. PMID- 3093223 TI - A 168-kilodalton protein of Mycoplasma pneumoniae used as antigen in a dot enzyme linked immunosorbent assay. AB - The attachment protein of Mycoplasma pneumoniae (molecular weight 168 kd) was used as antigen in a special enzyme-linked immunosorbent assay (dot ELISA) and compared with a sonicate of the whole organism. In control sera the intensity of the 168-kd band on immunoblots correlated well with the ELISA IgG values derived from isolated protein. The diagnostic significance of the 168-kd antigen was tested on paired sera from 33 patients with Mycoplasma pneumoniae infection (24 children, 9 adults). The ELISA values with the isolated protein were slightly lower than with cell antigen, but the protein also showed a lower basic activity in controls. In first sera of specimens of children collected within the first week of infection the 168-kd IgM response was more distinct than that to the whole cell antigen. Similarly the IgG response to the purified protein antigen differed significantly from the controls already in the first serum. In sera of adult patients the increased levels of IgG antibody were more evident with the 168-kd protein antigen. Use of the protein 168 kd as antigen increased the sensitivity of the ELISA for detecting early stages of disease, especially in children. PMID- 3093225 TI - In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium fortuitum and Mycobacterium chelonei to augmentin. PMID- 3093226 TI - Bacterial resistance after in vitro exposure to amikacin and netilmicin. PMID- 3093227 TI - Purification and structural analysis of pyocyanin and 1-hydroxyphenazine. AB - Pyocyanin and related members of the phenazine family are produced by Pseudomonas aeruginosa and have been associated with events of pathophysiological importance. Pyocyanin and its base hydrolysis product 1-hydroxyphenazine were purified to homogeneity by reverse-phase high-pressure liquid chromatography. Their mass spectrometric behaviour was examined with a view to evaluating the use of high resolution chromatography/mass spectrometry in studying phenazine-mediated effects in man. The molecular mass of naturally derived pyocyanin was determined as 210 Da by thermospray liquid chromatography/mass spectrometry and confirmed by desorption electron-impact mass spectrometry. Mass spectrometric data could not be obtained by fast-atom bombardment or desorption chemical ionisation, techniques commonly used to determine molecular mass of polar or thermally labile species. The thermal lability of underivatised pyocyanin precluded analysis by gas chromatography/mass spectrometry. In contrast to pyocyanin, mass spectrometric data were readily obtained for 1-hydroxyphenazine, using direct probe analysis as well as with gas and liquid chromatography inlet systems. PMID- 3093228 TI - Catabolism of glycoprotein glycans. Characterization of a lysosomal endo-N-acetyl beta-D-glucosaminidase specific for glycans with a terminal chitobiose residue. AB - An endo-N-acetyl-beta-D-glucosaminidase active towards oligosaccharides with a reducing terminal [bis(N-acetylglucosamine)]residue has been characterized in rat liver. The primary structure of its reaction products was determined using high resolution 1H-NMR spectroscopy. The enzyme is predominantly located in the lysosomal fraction, presents a maximum of activity at pH 3.5 and is completely inactive towards conjugated glycans, i.e. glycoproteins and glycopeptides as well as on glycoasparagines. These results support the existence of a new pathway for the degradation of glycoprotein glycans inside the lysosome. In particular, this enzymic activity may be the origin of oligosaccharides bearing a single terminal reducing N-acetylglucosamine residue which are excreted in the urine of patients with various exoglycosidase deficiencies. PMID- 3093229 TI - Coupling of carbon monoxide oxidation to CO2 and H2 with the phosphorylation of ADP in acetate-grown Methanosarcina barkeri. AB - Cell suspensions of Methanosarcina barkeri, grown on acetate, catalyzed the conversion of carbon monoxide and H2O to CO2 and H2 in stoichiometric amounts when methane formation was inhibited by bromoethanesulfonate. The specific activity was 80-120 nmol min-1 mg protein-1 at 5% CO in the gas phase. CO oxidation was coupled with the phosphorylation of ADP as indicated by a rapid increase of the intracellular ATP level upon start of the reaction. At least 0.1 mol ATP was formed/mol CO consumed. The onset of CO oxidation was also accompanied by an increase of the proton motive force (delta p) from 100 mV to 150 mV (inside negative). Addition of the uncoupler tetrachlorosalicylanilide to CO-metabolizing cells led to a rapid decrease of the ATP level and of delta p, and to an increase of the CO oxidation rate up to 70%. In the presence of the proton-translocating ATPase inhibitor N,N'-dicyclohexylcarbodiimide the phosphorylation of ADP was inhibited and CO oxidation slowed down, whereas delta p was almost unaffected. Inhibition of CO oxidation under these conditions was relieved by the addition of the protonophore tetrachlorosalicylanilide. The results indicate that in acetate-grown M. barkeri the free-energy change associated with the formation of CO2 and H2 from CO and H2O (delta G degrees = 20 kJ/mol) can be used to drive the phosphorylation of ADP and that the coupling proceeds via a chemiosmotic mechanism. A possible role of the carbon monoxide oxidation reaction as an energy-conserving site in acetate fermentation to CH4 and CO2 is discussed. PMID- 3093230 TI - Multispecific DNA methyltransferases from Bacillus subtilis phages. Properties of wild-type and various mutant enzymes with altered DNA affinity. AB - Temperate Bacillus subtilis phages SPR, phi 3T, rho 11 and SP beta code for DNA methyltransferases, each having multiple sequence specificities. The SPR wild type and various mutant methyltransferases were overproduced 1000-fold in Escherichia coli and were purified by three consecutive chromatographic steps. The stable form of these multispecific enzymes in solution are monomers with a relative molecular mass (Mr) of about 50,000. The methyl-transfer kinetics of the SPR wild-type and mutant enzymes were determined with DNA substrates carrying either none or one of the three recognition sequences (GGCC, CCGG, CCATGG). Evaluation of the catalytic properties for DNA and S-adenosylmethionine binding suggested that the NH2-terminal part of the protein is important for both non sequence-specific DNA binding and S-adenosylmethionine binding as well as transfer of methyl groups. On the other hand, mutations in the COOH-terminal part lead to weaker site-specific interactions of the enzyme. Antibodies raised against the purified SPR enzyme specifically immunoprecipitated the phi 3T, rho 11 and SP beta methyltransferases, bu failed to precipitate the chromosomally coded enzymes from B. subtilis (BsuRI) and B. sphaericus (BspRI). Immunoaffinity chromatography is an efficient purification step for the related phage methyltransferases. PMID- 3093231 TI - Characterization of a beta-galactosidase hybrid protein carrying the catalytic domain of Escherichia coli adenylate cyclase. AB - A hybrid protein of Escherichia coli, exhibiting both adenylate cyclase and beta galactosidase activities, was purified and characterized. This protein, obtained by genetic engineering, contained the first 556 amino acids of adenylate cyclase connected to the eighth-residue of beta-galactosidase through a pentapeptide Val Gly-Asp-Pro-Val. The fusion protein was less stable than the native beta galatosidase. Trypsin cleaved preferentially the adenylate cyclase moiety of the hybrid protein at a ratio of 1/50 (w/w). The kinetic properties of the hybrid protein were comparable, with a few exceptions, to those of native adenylate cyclase and beta-galactosidase. 'Truncated' adenylate cyclase was no longer sensitive to inhibition by excess ATP, which seems to indicate a second nucleotide binding site of wild-type adenylate cyclase. Photoirradiation of the hybrid protein with 8-azidoadenosine 5'-triphosphate inactivated the adenylate cyclase activity, leaving intact the beta-galactosidase activity. A radiolabeled ATP analog was incorporated after photoirradiation into the adenylate cyclase moiety of the fusion protein as shown by limited digestion with trypsin. PMID- 3093232 TI - Beta-alanine transport in synaptic plasma membrane vesicles from rat brain. Efflux, exchange and stoichiometry. AB - The efflux and exchange of beta-alanine were studied in synaptic plasma membrane vesicles from rat brain. The mechanism of beta-alanine translocation has been probed by comparing the ion dependence of net efflux to that of exchange. Dilution-induced efflux requires the simultaneous presence of internal sodium and chloride ions while influx is dependent on the presence of these two ions on the outside [Zafra, F., Aragon, M. C., Valdivieso, F. and Gimenez, C. (1984) Neurochem Res. 9, 695-707]. These data show that the release of beta-alanine occurs via the carrier system and that it is cotransported with sodium and chloride ions. beta-Alanine efflux from the membrane vesicles is stimulated by external beta-alanine. This exchange does not require external sodium and chloride but it is dependent on the external concentration of beta-alanine. Half maximal stimulation is obtained at a beta-alanine concentration similar to the Km for beta-alanine influx. Results of the direct measurements of the coupling of sodium and chloride to the transport of beta-alanine by using a kinetic approach allow us to propose a stoichiometry for the translocation cycle catalyzed by the beta-alanine transporter of three sodium ions and one chloride ion per beta alanine zwitterion. To account for all the observed effects of external ions, beta-alanine concentrations and membrane potential on beta-alanine influx and efflux, a kinetic model of the Na+/Cl-/beta-alanine cotransport system is discussed. PMID- 3093233 TI - Immunoelectron microscopic demonstration of the exocytosis of dense granule contents into the secondary parasitophorous vacuole of Sarcocystis muris (Protozoa, Apicomplexa). AB - Merozoites of the parasitic protozoon Sarcocystis muris (Apicomplexa) possess three types of characteristic organelles with electron dense contents named rhoptries, micronemes, and dense granules, which are supposed to be involved in the parasite-host cell interactions during and after invasion. Dense granules were purified from a merozoite homogenate by centrifugation on a sucrose density gradient. It was shown by SDS polyacrylamide gel electrophoresis that they contain a major protein of 21 kDa. Polyclonal antibodies raised against this protein were applied to ultrathin frozen and Lowicryl-K4M-embedded sections of the parasite before and after host cell invasion. Dense granules were distinctly labeled by immunogold before and after invasion. After host cell invasion the parasite is enclosed in a secondary parasitophorous vacuole which contains an electron-dense material. This deposition was heavily labeled by anti 21 kDa antibodies which clearly demonstrated that the dense granule contents is released into the secondary parasitophorous vacuole. PMID- 3093234 TI - Interaction of Trypanosoma cruzi with heart muscle cells: ultrastructural and cytochemical analysis of endocytic vacuole formation and effect upon myogenesis in vitro. AB - The process of interaction of bloodstream trypomastigotes of three different strains of Trypanosoma cruzi with heart mouse muscle cells in primary cultures, was analyzed. Differences were found in the ability of the parasites to infect the cells. Those from the Colombiana strain were more infective than those from the Y and CL strains. Infection of the cells with parasites of the Colombiana strain, but not with those of the Y strain, interfered with the normal myogenic process. Transmission electron microscopy of thin sections of heart muscle cells kept in contact with parasites for 18 h showed that many parasites are found within membrane-bounded endocytic vacuoles. Cytochemical localization of Ca2+ Mg2+-ATPase, adenylate cyclase and anionic sites (labelled with cationized ferritin) indicate that these components of the plasma membrane are not found in the membrane which lines the endocytic vacuole. PMID- 3093235 TI - Endocytosis of a monoclonal antibody recognising a cell surface glycoprotein antigen visualised using fluorescent conjugates. AB - The endocytosis of a monoclonal antibody recognising a cell surface glycoprotein antigen has been investigated using several different fluorescent conjugates. These conjugates have been employed for both fluorescence microscopy to show the qualitative changes in distribution of antibody conjugates during endocytosis, and also flow cytofluorimetry to show the quantitative changes in fluorescence intensity associated with this redistribution. Using an antibody directly labelled with fluorescein it was difficult to demonstrate endocytosis due to the inability to distinguish clearly between internal and external fluorescence. However, a fluorescein-HSA-antibody conjugate which was heavily quenched at the cell surface was endocytosed and degraded during incubation at 37 degrees C for 4 h and was then visualised in a perinuclear distribution by the addition of agents to modify intracellular pH. This experiment demonstrated that such conjugates became localised within an acidic internal compartment. A tetramethylrhodamine HSA-conjugate also demonstrated a similar perinuclear distribution but without the addition of endosomal pH modifiers. When used in conjunction with a fluorescein rabbit anti-HSA second label this conjugate also showed that not all conjugate was endocytosed during a 4-h period; some conjugate remained bound to the cell surface. These experiments suggested that endocytosis in this system differs from receptor-mediated endocytosis via coated pits which is reported to be more rapid and complete. PMID- 3093236 TI - Effect of flunarizine on regional cerebral blood flow in common and complicated migraine. Pilot study. AB - Alterations of regional cerebral blood flow (rCBF) are at least epiphenomena of common and complicated migraine, but may lead to serious clinical complications. Since flunarizine seems to be effective in migraine prevention it may exert a beneficial influence on rCBF in migraine as well. rCBF was assessed using the 133Xe inhalation method in 5 patients with common and 8 patients with complicated migraine. Measurements were done interictally prior and after therapy with 15 mg flunarizine p.o. daily over a period of 4 weeks. Major abnormalities of grey matter flow were observed even interictally. Significant improvement of rCBF in initially hypoemic regions may be attributed to flunarizine therapy. These preliminary data suggest that calcium entry blockers may prevent the ischemic complications of migraine. PMID- 3093237 TI - Effects of lithium carbonate on the clinical picture and the sleep of depressive patients. AB - 5 patients with endogenous depression of uni- and bipolar type, classified according to sleep characteristics as normo- (1), hypo- (3) and hypersomniacs (1), were treated for 3 weeks with a daily dose of 900 mg lithium carbonate. Polygraphic sleep recordings were taken in every patient in the course of 3 placebo nights, 3 nights during therapy and 2 registrations after lithium carbonate was discontinued. Before therapy, a prolonged sleep and a shortened REM latency were observed, which were changed in the course of the treatment especially in the normosomniac patient. In the other examined sleep parameters (total sleep time, sleep efficiency, percentage of REM sleep, slow wave sleep), discrepancies among hypo-, hyper- and normosomniac patients were present. From the clinical point of view all patients showed an improvement subjectively and objectively measured by means of Hamilton and Beck questionnaires for depression. This study emphasizes the necessity of administering daily lithium carbonate doses higher than 900 mg because of only a mild therapeutic effect. PMID- 3093238 TI - Clinical studies of 4 methods of bowel preparation in colorectal surgery. AB - A prospective study was carried out to compare the effectiveness of 4 commonly employed methods of bowel preparation before colorectal surgery: mechanical, mechanical with an antibiotic against aerobes (neomycin), mechanical with another antibiotic against anaerobes (metronidazole), and finally mechanical with a combination of neomycin and metronidazole. The use of mechanical preparation as the sole method was discontinued half-way through the study for ethical reasons. 53 bowel preparations were carried out on 31 patients, 7 adults and 24 children with mainly Hirschsprung's disease and imperforate anus. The incidence of postoperative infections ranged from 40 to 46% in the first 3 groups, in contrast to only 6% in the fourth group (p less than 0.05). The majority of the organisms isolated were gram-negative bacteria. The results show that a combination of mechanical bowel washout with oral neomycin and metronidazole is a most effective method of bowel preparation before colorectal surgery. PMID- 3093239 TI - Calcium absorption following small bowel resection in man. Evidence for an adaptive response. AB - Seventeen patients who had undergone extensive small bowel resection were studied for calcium absorption (FACa) and plasma vitamin D metabolites. FACa was measured by a double radio-tracer technique and expressed as percentage of total oral dose. FACa was decreased compared with controls (34%, range: 3-46 v 65%, range: 57-73, P less than 0.01). A positive correlation (r = 0.49, P = 0.05) was found between FACa and the remaining length of small bowel (SBL). As wide variations in both SBL and duration after surgery were observed among the seventeen investigated patients, we were led to individualize less heterogeneous subgroups of patients. Better correlations were found when the patients were divided into two subgroups according to whether the time interval between the resection and the investigation was shorter (r = 0.75, n = 11, P less than 0.02) or longer (r = 0.89, n = 6, P = 0.05) than 2 years. In thirteen patients who had a SBL shorter than 100 cm, a positive correlation was observed between FACa and the time interval after surgery (months): r = 0.65, P less than 0.05. Plasma 1,25 (OH)2D was markedly reduced in the whole group (31 pmol l-1, range: 8-108) compared with controls (103 pmol-1, range: 59-134, P less than 0.01). The present study shows that in extensively small bowel resected patients, calcium absorption is reduced, the alteration being dependent both on the length of the remnant small bowel and on the time after surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093240 TI - Primary hyperparathyroidism: evaluated by 47calcium kinetics, calcium balance and serum bone-Gla-protein. AB - Combined 47Calcium kinetic and calcium balance studies with correction for dermal calcium loss were performed in thirteen patients with primary hyperparathyroidism (PHP), in whom serum bone-Gla-protein (S-BGP) was measured, and in ten matched controls. Dietary calcium was normal in PHP but both net (7.9 +/- 1.4 mmol Ca day 1 in PHP v. 3.5 +/- 0.9 mmol Ca day-1 in normals (mean +/- SE] and true (11.1 +/- 1.6 v. 6.8 +/- 0.9 mmol Ca day-1) intestinal absorbed calcium were enhanced (P less than 0.05). The renal calcium excretion (10.9 +/- 0.8 v. 5.1 +/- 0.4 mmol Ca day-1, P less than 0.001) and the dermal calcium loss (2.5 +/- 0.3 v. 1.5 +/- 0.1 mmol Ca day-1, P less than 0.02) were increased in PHP. Both patients and controls were in a negative calcium balance (P less than 0.01 and P less than 0.001, respectively) without any difference between the groups (P greater than 0.10). Mineralization (12.0 +/- 1.7 v. 4.8 +/- 0.8 mmol Ca day-1, P less than 0.02) and resorption rates (17.6 +/- 2.5 v. 7.9 +/- 0.6 mmol Ca day-1, P less than 0.02) were increased in PHP and S-BGP correlated positively to both variables (r = 0.64, P less than 0.05 and r = 0.62, P less than 0.05, respectively). Serum immunoreactive parathyroid hormone correlated positively to serum calcium (r = 0.69, P less than 0.01) but not to the calcium kinetic data. PMID- 3093241 TI - Inducing efficacy of ethanol on hepatic drug metabolizing enzymes in patients. AB - In liver biopsy material of eighty-nine patients with suspected liver disease the drug-metabolizing function was investigated. The capacity of the liver to oxidatively metabolize drugs was assessed by determination of cytochrome P-450 dependent monooxygenase activity in vitro. The biotransformational function of these microsomal enzymes was tested with compounds representing the activity of oxidative drug metabolism (7-ethoxycoumarin, p-nitroanisol and cytochrome c). From the eight-nine patients sixty-one had various liver diseases not related to ethanol and twenty-eight abused ethanol. When both groups were matched for age, sex, smoking, treatment with sedatives, drugs and degree of liver damage the alcoholic group had significantly higher activities of 7-ethoxycoumarin O deethylase (EOD: 76.9 +/- 31.1 pmol min-1 mg-1 protein, mean +/- SD) than the non alcoholic liver disease group (42.7 +/- 14.1). The inducing effect of ethanol was most striking on the EOD activity, less for the O-demethylation of p-nitroanisol (PNA) and not present for the NADPH-cytochrome c reductase. The induced patients were analysed in detail to find out which factors were responsible for the observed scatter of enzyme activities within the alcoholic group. Alcoholics with fatty liver (n = 7) had the highest EOD activities (108.9 +/- 25.0), patients with alcoholic hepatitis (n = 10) had significantly less activity (66.0 +/- 1.9) than the former group. However, alcoholics without liver damage (n = 6) had activities not significantly different (46.0 +/- 15.8) from controls (39.4 +/- 9.1). These subgroups among the alcoholics were comparable in terms of sex, age, smoking and drinking habits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093242 TI - Differentiation of bone marrow cells from myelodysplastic patients in the presence of 1,25 dihydroxyvitamin D3 or 13-cis retinoic acid. AB - The separate effects of vitamin D3 (1,25(OH)2D3) and 13-cis retinoic acid on the differentiation in liquid culture of marrow cells from seven patients with myelodysplastic syndrome (MDS) were studied. Following incubation with 1,25(OH)2D3, an increasing number of myeloid cells acquired the morphological appearance of mature monocyte-macrophages and reacted positively to fluoride sensitive naphthyl acetate esterase and specifically bound My4 monoclonal antibody (McAb). Incubation of bone marrow cells with 13-cis retinoic acid enhanced the number of cells with the morphological appearance of metamyelocytes and mature granulocytes as well as those that reacted positively with AS-D naphthol chloroacetate esterase. The results suggest that the differentiation pattern of myeloid precursor cells from MDS patients can be modulated by 1,25(OH)2D3 and 13-cis retinoic acid. PMID- 3093243 TI - Effects of thyroid hormone and beta-adrenoceptor blocking agents on urinary excretion of 3-methylhistidine and plasma amino acids in man. AB - The aim of this investigation was to study the effect of beta-adrenoceptor blockade on alterations in protein metabolism induced by administration of 3,5,3' triiodothyronine (T3) to man. Urinary excretion of 3-methylhistidine and plasma concentrations of amino acids were measured in seven healthy subjects following 1 weeks's administration of T3 alone or T3 in combination with the selective beta 1 adrenoceptor blocking agent metoprolol or the non-selective beta-adrenoceptor blocking agent propranolol. Urinary excretion of 3-methylhistidine and plasma concentrations of valine, methionine, lysine, tyrosine, phenylalanine, isoleucine, leucine, and total essential and branched chain amino acids increased following administration of T3, probably in part reflecting accelerated muscle proteolysis. Neither metoprolol nor propranolol normalized 3-methylhistidine excretion or plasma concentrations of amino acids during T3 treatment. The results indicate that metabolic alterations induced by T3 and giving rise to enhanced 3-methylhistidine excretion and elevated concentrations of plasma amino acids are not normalized by beta-adrenoceptor blockade. PMID- 3093244 TI - Antipyrine clearance and metabolite formation: the influence of liver volume and smoking. AB - The influence of liver volume and cigarette smoking on antipyrine clearance and metabolite formation was studied in seventeen volunteers (eight smokers, nine non smokers). Inter-test coefficient of variation of liver volume (as determined by ultrasound) was 6.3%. The mean antipyrine clearance was 49.3 +/- 18.3 ml min-1 and when normalized for liver volume 36.1 +/- 10.1 ml min-1 l-1. The antipyrine clearance per unit volume of liver was significantly higher in smokers (43.0 +/- 10.5 ml min-1 l-1), than in non-smokers (30.0 +/- 4.6 ml min-1 l-1) (P less than 0.01). No significant difference was found between the two groups as to the excreted amounts of 4-hydroxyantipyrine (OHA), norantipyrine (NORA), and 3 hydroxymethylantipyrine (HMA). Normalized for liver volume the mean clearances for production (Clm) of these metabolites were significantly higher in the group of smokers than in the group of non-smokers. The greatest change was observed for OHA formation. However, analysis of variance showed that the differences in the percentages of change of the mean Clm of these metabolites in the two groups are not significant. PMID- 3093245 TI - Detection of rearranged T cell receptor beta-chain gene and induction of cytolytic function in interleukin 2-responsive day 14-15 murine fetal thymocytes. AB - A subpopulation of interleukin 2 (IL 2) receptor-positive day 14-15 murine fetal thymocytes can be induced by recombinant IL 2 to proliferate over prolonged time periods in dissociated cell cultures. The proliferating day 14-15 fetal thymocytes exhibit no cytolytic effector function, nor do they rearrange T cell receptor beta chain genes. This contrasts with thymic organ cultures in which day 14-15 thymocytes do rearrange beta chain genes and give rise to immunocompetent cells. However, such events can also take place in dissociated cell cultures, provided the IL 2-responsive thymocytes are cultured on syngeneic feeder cells in the presence of IL 2 and the mitogen concanavalin A. Under such conditions rearrangement of the beta chain gene complex becomes detectable and cytolytic effector cells are generated. The frequency of inducible cytolytic precursor cells in day 14-15 thymocytes is 1/7000. These data either imply that immunocompetent cells are already present in the day 14-15 fetal thymus, or differentiation from precursors to immunocompetent cells must occur in dissociated cell cultures. PMID- 3093246 TI - Interleukin 2 is a proliferative signal for B cells from autoimmune mice. AB - T cells from murine lupus strains manifest complex defects in interleukin 2 (IL 2) production and receptor expression. The capacity of B cells from such mice to utilize IL 2 as a growth factor has not been previously reported and is examined herein. Anti-Thy-1.2 plus complement-treated spleen cells from 6-8-week-old autoimmune MRL-lpr/lpr mice and from age and sex-matched immunologically normal CBA/J mice were cultured with lipopolysaccharide (LPS) for 36 h and analyzed for the expression of IL 2 receptors using the monoclonal antibody 7D4. The percentage of B cells expressing IL 2 receptors was comparable in MRL-lpr/lpr and CBA/J mice. In contrast to those from CBA/J, BALB/c and (BALB/c X NZW)F1 mice, LPS-stimulated B cells from MRL-lpr/lpr and from (NZB X NZW)F1 mice were capable of proliferating in response to IL 2. Fractionation of MRL-lpr/lpr B cells using Percoll gradient density separation demonstrated that the IL 2-responsive population consisted predominantly of large cells. In addition, unfractionated B cells from MRL-lpr/lpr mice were found to be substantially more responsive to IL 2 than those from CBA/J and BALB/c mice following activation with anti immunoglobulin plus LPS. The hyper-responsiveness to IL 2 may be a consequence of the state of activation of autoimmune B cells and is of potential importance in the pathogenesis of systemic lupus erythematosus. PMID- 3093247 TI - Early arrest of B cell development in nude, X-linked immune-deficient mice. AB - Mice simultaneously expressing the nude and xid mutations have a severe deficit of both mature T and B cells. We now report studies designed to determine at which point in B cell differentiation development is arrested. Nude-xid mice have normal numbers of hematopoietic colony forming units (CFU-s) but lack two early pre-B cell markers: susceptibility to transformation by Abelson murine leukemia virus (A-MuLV) and production of cytoplasmic mu (C mu) heavy chain. Thus, there is a defect in lymphocyte development prior to or early in pre-B cell differentiation but after hematopoietic stem cell formation. The monoclonal reagents DNL 1.9, 14.8 and RA3-3A1/6.1, which react with the surface protein B220 (Ly5) on pro-B, C mu- pre-B, C mu+ pre-B, and surface Ig+ B cells, revealed the presence of positive cells in nude-xid mice. The bone marrow of nude-xid mice contains more B220+ cells than C mu+ cells. Our data suggest that the developmental block in these mice occurs at the earliest identifiable step in the B lymphocyte lineage, after the appearance of B220+ C mu- pro-B cells, but before the differentiation of C mu-bearing (pre-B) cells. PMID- 3093248 TI - In vivo administration of interleukin 2 stimulates mitosis in thymus and bone marrow. AB - We have used short-term, high-density cultures to demonstrate that interleukin 2 (IL 2) in picomolar amounts causes entry of approximately 2% of thymocytes from 3 month-old rats into mitosis. Newborn and fetal animals show a higher response reflecting a greater proportion of cells which have been shown to express IL 2 receptors at this age. In vivo administration of nanogrammes of IL 2 or injection of rats with syngeneic spleen cells which had been stimulated in vitro with concanavalin A to release IL 2 were also shown to increase the proliferation of both thymus and bone marrow cells. This suggests that IL 2, in amounts which could be produced by peripheral lymphoid tissue during immune responses, could act to increase the turnover of lymphocytes in bone marrow and thymus. PMID- 3093249 TI - The effect of long-term treatment with antisecretory and antiulcer drugs on gastric secretory and motor responsiveness to caerulein in rats with chronic ulcers. AB - In the present paper the gastric secretory and motor responsiveness to a gastrin like peptide, caerulein, was assessed in rats with a chronic gastric ulcer induced by 'isolation', 48 h after completing prolonged treatments (30 and 60 days) with cimetidine (80 and 160 mg/kg), pirenzepine (8 and 16 mg/kg) and sulglycotide (160 mg/kg) administered orally as a single daily dose. After a 30 day pretreatment with both doses of cimetidine, gastric acid secretion was inhibited and the pylorus spasmogenic activity induced by caerulein was enhanced. The gastric effects of the peptide were not modified by pirenzepine pretreatment while an antisecretory action was shown by sulglycotide after the completion of prolonged treatment (60 days). The ulcers were significantly reduced by cimetidine (low dose) and sulglycotide after 30 day pretreatment. The effects are more likely to be related to the treatment than to the presence of the drugs on gastric receptors. PMID- 3093250 TI - Differences in the ability of salbutamol to prevent and reverse LTC4-induced contractions of the guinea-pig isolated trachea: influence of l-serine borate. AB - In the presence of l-serine borate, salbutamol was much more effective in reversing rather than preventing LTC4-induced contractions of guinea-pig trachea. This suggests that different mechanisms are involved in initiating versus maintaining LTC4-induced contractions. In addition, the ability of salbutamol pretreatment to prevent LTC4-induced contractions was reduced substantially in the presence of l-serine borate, suggesting that the metabolites of LTC4 (LTD4 and LTE4) are more sensitive to inhibition by beta-adrenoceptor agonists than is LTC4 itself. PMID- 3093252 TI - Apomorphine does not decrease tissue levels of tetrahydrobiopterin in vivo. AB - It was reported that R(-)apomorphine and other catechols are potent inhibitors of dihydropteridine reductase in vitro. It was suggested that decreased levels of tetrahydrobiopterin may represent a mechanism by which R(-)apomorphine inhibits catecholamine synthesis in vivo. This paper demonstrates that tetrahydrobiopterin levels are not affected either in vitro (PC12 cells) or in vivo (rat liver and corpus striatum) by treatment with R(-)apomorphine, whereas DOPA (3,4 dihydroxyphenylalanine) production (PC12 cells, corpus striatum) is reduced. This indicates that R(-)apomorphine does not inhibit DOPA production by reducing 6(R) L-erythro-tetrahydrobiopterin) levels. PMID- 3093251 TI - D-1 receptor supersensitivity in the rat striatum after unilateral 6 hydroxydopamine lesions. PMID- 3093253 TI - Benzodiazepine cross-tolerance in mice extends to sodium valproate. AB - Slow intravenous infusion of pentylenetetrazol was used to measure the convulsive threshold in mice. The anticonvulsant effects of clobazam, clonazepam, diazepam, lorazepam, sodium phenobarbitone and sodium valproate were assessed in naive animals and compared with the effects of the same compounds in animals which had been pretreated (twice daily for 3 days) with one of the benzodiazepines or sodium valproate. Cross-tolerance was observed between all the benzodiazepines but not between benzodiazepines and sodium phenobarbitone. Animals pretreated with the benzodiazepines were cross-tolerant to valproate, but the converse was not true; nor did sodium valproate induce tolerance to itself. PMID- 3093254 TI - Effects of parathyroidectomy in pregnant rats on the luteinizing hormone and follicle-stimulating hormone response to synthetic luteinizing hormone-releasing hormone in the infantile offspring. AB - Effects of parathyroidectomy (PTx) in the rat at the 5th day of gestation on the functional development of gonadotrophin secretion in the infantile offspring was examined. A single subcutaneous injection of 10 micrograms/kg of luteinizing hormone-releasing hormone (LHRH) induced a significant increase in serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) in control- and PTx-F1 male and female rats already at 3 days of age. The response in female rats was greater than in males at all ages examined. In the control- and PTx-F1 rats, age related increase in the responsiveness to LHRH was observed in both sexes for LH but only in females for FSH. However, LH and FSH release by LHRH in the PTx-F1 female rats was significantly lower than that in control females at 14 and 22 days of age. In the PTx-F1 male rats, only FSH response to LHRH showed a tendency to decrease at 22 days of age. Serum calcium levels in 3-day-old PTx-F1 male and female rats were significantly lower than those in controls but only a slight decrease was observed in the PTx-F1 rats at other ages. The present results indicated that a low serum calcium environment during fetal life in the rat affects the functional development of pituitary responsiveness to LHRH, particularly in females. PMID- 3093255 TI - Litorin (bombesin family) inhibits thyrotropin secretion in rats. AB - The effects of the peripheral administration of litorin on thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) secretion were studied in rats. Litorin (400 micrograms/kg) was injected iv, and the rats were serially decapitated. TRH, TSH and thyroid hormone were measured by radioimmunoassay. The hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after litorin injection, whereas its plasma concentration tended to decrease, but not significantly. The plasma TSH levels decreased significantly in a dose-related manner with a nadir at 20 min. after the injection. The plasma thyroid hormone levels showed no changes. The plasma ir-TRH and TSH responses to cold were inhibited by litorin, but the plasma TSH response to TRH was not affected. In the pimozide- or para-chlorophenylalanine-pretreated group, the inhibitory effect of litorin on TSH levels was prevented, but not in the L-DOPA- or 5 hydroxytryptophan-pretreated group. These drugs alone did not affect plasma TSH levels in terms of the dose used. The inactivation of TRH immunoreactivity by hypothalamus or plasma in vitro after litorin injection did not differ from that of the saline-treated group. These findings suggest that litorin acts on the hypothalamus to inhibit TRH release, and that its effects are modified by amines of the central nervous system. PMID- 3093256 TI - The effects of prostaglandin synthetase inhibitor indomethacin on the hypothalamic and neurohypophysial oxytocin content in euhydrated and dehydrated male white rats. AB - Rats euhydrated or dehydrated up to eight days were given intraperitoneally indomethacin (IM) twice daily in a dose of 0.2 mg/100 g of initial body weight. A single dose of IM injected to euhydrated animals did not affect the neurohypophysial oxytocic activity but decreased that potency in the hypothalamus. When IM was administered repeatedly during four or eight days, the hypothalamic oxytocic activity did not differ from the respective controls; under such conditions the oxytocic activity in the neurohypophysis increased progressively. Under conditions of dehydration the known depletion of hypothalamic and neurohypophysial oxytocin storage was not affected by indomethacin. It is therefore suggested that impulses of osmoreceptor origin are of distinct importance in determining the function of oxytocinergic neurones under conditions of inhibited prostaglandin synthesis. PMID- 3093257 TI - Reorganization of alpha-actinin and vinculin in living cells following ATP depletion and replenishment. AB - Although it is known that the depletion of cellular ATP induces a dramatic, reversible disruption of microfilament structures, the morphological pathway remains obscure. I have studied this process by following directly the dynamic redistribution of fluorescently labeled alpha-actinin and vinculin which had been microinjected into living mouse 3T3 fibroblasts. Before treatment, microinjected alpha-actinin displayed characteristic distribution along stress fibers, whereas vinculin was localized predominantly at adhesion plaques. The first response after adding NaN3 and 2-deoxyglucose was the retraction of lamellipodia, followed, over a period of 2 h, by a dramatic contraction of stress fibers and loosening of focal contacts. Vinculin plaques shrank from an elongated shape to small aggregates. During recovery, which was initiated by removing NaN3 and 2 deoxyglucose from the medium, lamellipodia appeared rapidly and alpha-actinin dispersed from contracted aggregates. Some partially dispersed aggregates later served as initiation sites for the formation of stress fibers. The recovery of vinculin plaques occurred predominantly through direct elongation, and focal contacts developed concomitantly. A small fraction of vinculin aggregates, however, moved into the perinuclear region without developing into adhesion plaques, and some new vinculin plaques formed de novo. Possible mechanisms involved and relationships to disruptions induced by other agents are discussed. PMID- 3093258 TI - Respiratory flutter during carbon dioxide rebreathing in patients with obstructive sleep apnea syndrome. AB - In order to detect the dysfunction of the upper airway muscles in awake patients with obstructive sleep apnea syndrome (OSAS), we examined the effect of a chemical stimulus (CO2) on flow-volume loops obtained during tidal breathing. Six flow-volume curves during forced maneuvers and six flow-volume tracings during rebreathing of CO2 were recorded in 20 patients with OSAS. All patients had numerous obstructive apneas (mean apnea index 61 +/- SD 33, percentage of obstructive apneas 76 +/- 29) associated with moderate to severe degrees of arterial oxygen desaturation. Of the 18 patients in whom at least six flow-volume loops could be obtained during CO2 rebreathing, 13 exhibited respiratory flutter (range: grade 1 to 6) during tidal breathing in the flow-volume tracing (RF VtCO2). The greater the degree of RF VtCO2 during wakefulness, the less was the lowest oxygen saturation (LSaO2) during sleep. In fact, all four patients with RF VtCO2 score 6 had LSaO2 below 30%. PMID- 3093259 TI - Tectal cells of origin of predorsal bundle in rat: location and segregation from ipsilateral descending pathway. AB - In rats, as in other mammals, one of the principal projections of the superior colliculus (SC) crosses the midline in the dorsal tegmental decussation to join the contralateral predorsal bundle (PDB). The cells of origin of this pathway were studied by injections of retrograde tracers (true blue or wheatgerm agglutinin-conjugated horseradish peroxidase) into the PDB rostral to its major fields of termination. Labelled cells were plotted with respect to fibre layers within the SC. The majority of labelled cells in the contralateral SC were located within the stratum album intermediale (SAI), between the fasciles oriented caudorostrally in that layer. They were of a wide range of sizes, and were much more numerous in lateral SC (where the SAI is broader) than in medial SC. The remaining labelled cells were found mainly in the deep layers. The effects of midline knife-cuts made prior to the injection of tracer suggested that most of the labelled SAI cells, but few of the deep-layer cells, projected across the midline in the dorsal tegmental decussation. Double-labelling procedures were used to investigate whether the cells of origin of the PDB send collaterals in the ipsilateral descending pathway of the SC. Injections of diamidino-yellow into the terminal regions of this pathway labelled very few PDB cells, although large numbers of other tectal cells were labelled. In contrast, extensive double labelling was observed after control injections of diamidino yellow into the ipsilateral ascending pathway in the ventral diencephalon. These findings suggest that there is anatomical, and therefore perhaps functional, segregation of descending output channels from the superior colliculus in rat. This suggestion receives some support from comparison of the present results with those of tectal stimulation studies. Stimulation in the vicinity of lateral SAI gives contralaterally-directed head and body movements characteristic of orienting and approach, whereas stimulation in other tectal regions that contain predominantly the cells of origin of the ipsilateral descending pathway can give movements resembling avoidance or escape. PMID- 3093260 TI - Immunoelectron microscopic observations of hypothalamic TRH-containing neurons in rats. AB - Immunoreactive TRH-containing neurons and their synaptic associations were studied electron microscopically in the paraventricular nucleus (PVN) and dorsomedial nucleus (DMH) of the rat hypothalamus. In propylthiouracil (PTU) treated rats, the immunoreactive cell bodies in the PVN appeared to be activated, showing a hypertrophic perikaryon, well developed Golgi bodies and numerous secretory granules. No such alterations were evident in the TRH neurons in the DMH. These findings suggest that the PVN-TRH neurons are involved in the hypothalamic-hypophysial-thyroid axis. Further, it was shown that unlabeled nerve terminals containing small and large clear vesicles make synaptic contacts with the TRH perikarya in the PVN. Thus it is likely that PVN-TRH neurons are regulated both by thyroid hormones and by other neuronal signals. In the DMH, unlabeled nerve terminals containing small and large clear vesicles, and immunoreactive terminals form synapses with TRH neurons. Thus the DMH-TRH neurons may be under dual neuronal control. It was further noted that in the DMH and PVN, TRH nerve terminals make synaptic contacts with other unlabeled neurons. It is evident that TRH acts as a neurotransmitter or neuromodulator, although the origin of TRH terminals should be elucidated. PMID- 3093261 TI - Metabolic anatomy of generalized bicuculline seizures in the newborn marmoset monkey. AB - Sustained convulsive seizures were induced with bicuculline in ketamine anesthetized marmoset monkeys aged 7 to 18 days. Relative 2-deoxyglucose metabolism was compared in convulsing (N = 9) and control (N = 6) animals. Convulsions were accompanied by striking focal increases in cerebral 2 deoxyglucose uptake which were remarkably consistent from animal to animal. Increased 2-deoxyglucose uptake in broad cortical regions (2- to 3-fold) suggests that cortical mechanisms can be important, even in neonatal seizures. The hippocampus and other limbic system structures were markedly activated, as were nuclei of the basal ganglia and thalamus. In contrast, sensory systems were less affected. No increase in 2-deoxyglucose uptake was found in the lateral geniculate nuclei, and a 22% decrease was found in the inferior colliculus (central core). Increased uptake was found in several white matter regions, and activation of the corpus callosum (2.6-fold) was comparable to that found for many gray matter regions. Our results show that generalized bicuculline seizures can produce striking focal increases in cerebral 2-deoxyglucose metabolism in brain regions known to be vulnerable to epileptic brain damage. PMID- 3093262 TI - Antagonism by thyrotropin-releasing hormone (TRH) of pentobarbital-induced hypothermia in rats with brain lesions. AB - Anesthesia with a large dose of pentobarbital (55 mg/kg, i.p.) caused a sustained decrease in brain temperature (Tb), which was monitored with a probe placed in the midbrain reticular formation. The administration of TRH to the lateral ventricle antagonized this hypothermia. None of the acute surgeries examined in this paper (adrenal-demedullectomy, septal knife cuts, electrolytic lesions of the hypothalamus and midbrain knife cuts) had any essential effect on this antagonism by TRH. These results suggest that centrally-administered TRH exerts its effect on thermoregulation, at least in part, through brain structure(s) caudal to the midbrain. PMID- 3093263 TI - Effects of thyroidectomy and thyroxine replacement on the responsiveness of the anterior pituitaries from male rats to thyrotropin-releasing hormone in vitro. AB - Thyroidectomy decreased prolactin concentrations in the anterior pituitary (AP) and serum of the male rat. The amount of basal and thyrotropin-releasing hormone (TRH)-stimulated release of prolactin by AP in vitro was lower in thyroidectomized (Tx) rats than in sham Tx rats. These results suggest that the inhibitory effects of thyroidectomy on pituitary and serum prolactin in male rats are mediated in part by the reduction of the production and spontaneous release of prolactin and the responsiveness of prolactin to TRH. PMID- 3093264 TI - Possible involvement of protein kinase C in the stimulation of amino acid transport by phorbol ester, platelet-derived growth factor and A23187 in Swiss 3T3 cells. AB - Stimulation of amino acid transport induced by phorbol-12,13-dibutyrate, platelet derived growth factor or A23187 was not observed in cells lacking protein kinase C. On the other hand, stimulation of transport by epidermal growth factor or insulin was not affected. These results suggested that the stimulation of amino acid transport is mediated by at least two separate pathways. PMID- 3093265 TI - Aplysianin-A, an antibacterial and antineoplastic glycoprotein in the albumen gland of a sea hare, Aplysia kurodai. AB - Aplysianin-A, an antibacterial and antineoplastic factor in the albumen gland of the sea hare Aplysia kurodai, was isolated. It had a molecular weight of approximately 320 kD and consisted of subunits with a molecular weight of 85 kD. It contained 9.8% neutral sugar. Aplysianin A showed 50% inhibition of Bacillus subtilis growth at a concentration of 4 microgram protein/ml and 50% lysis of murine MM46 tumor cells at 14 ng protein/ml. A partial identity of antigenic specificity of the purified specimen with an antineoplastic factor from Aplysia eggs was observed in immunodiffusion tests. PMID- 3093267 TI - Matrix fibronectin disruption in association with altered endothelial cell adhesion induced by activated polymorphonuclear leukocytes. AB - Sequestration of activated polymorphonuclear leukocytes (PMN) within the lung microcirculation may contribute to pulmonary vascular injury following trauma, sepsis, or disseminated intravascular coagulation. In this study cultured rat endothelial cells were utilized to evaluate the effect of PMN activation on endothelial cell attachment. The concept that disruption of the extracellular fibronectin matrix is associated with altered endothelial cell adhesion was also tested. Rat endothelial cells were grown in culture and identified by morphological techniques as well as immunofluorescent staining of Factor VIII R:Ag. Endothelial cells were labeled with 51Cr in order to establish a cell injury assay based on release of free 51Cr or cell-associated 51Cr. PMN activation was verified microscopically and by chemiluminescence activity following phorbol myristate acetate (PMA) or opsonized zymosan exposure. Following incubation with PMA, the leukocytes aggregated, chemiluminesced vigorously, and caused endothelial cell injury and detachment as determined by release of 51Cr-labeled endothelial cells. PMNs exposed to serum-treated zymosan exhibited a more modest chemiluminescence burst which was consistent with their decreased activity to injure the endothelial monolayer. With PMA activation the degree of endothelial detachment from the monolayer increased as a function of time with a plateau observed by 3 hr. Microscopic immunofluorescent analysis of extracellular fibronectin in endothelial cell cultures revealed disruption of the fibrillar matrix fibronectin after incubation with PMA-activated neutrophils in association with endothelial cell disadhesion. Thus, exposure of activated rat PMN to rat endothelial cells in culture induces endothelial damage and an associated disruption of the fibronectin matrix which may contribute to endothelial cell detachment. PMID- 3093268 TI - Density-dependent contraction of the endothelial nascent histamine pool by exogenous heparin. AB - The aortic endothelial cell nascent histamine pool has been implicated in the control of vessel wall permeability under conditions of stress and injury. We report the contraction of this histamine pool in low density bovine aortic endothelial cell (BAEC) cultures by exogenous heparin. Untreated BAEC exhibit a decline in histamine content in 3-day cultures with increasing plating density between 1000 and 16,000 cells/cm2. Heparin abolished this density-related difference by effecting a 67% contraction of the histamine pool in the lowest density cultures. This effect was reversible and specific to heparin. At a confluent density, endothelial cells secrete heparin-like glycosaminoglycans which affect smooth muscle and endothelial metabolism. We propose that the metabolic effects of exogenous heparin, and perhaps endogenous heparins, extend to specific modulations of the BAEC nascent histamine pool. PMID- 3093266 TI - Virus-immune T cells and the major histocompatibility complex: evolution of some basic concepts over the past two years. PMID- 3093269 TI - [Antiaggregation action and pharmacokinetics of lysine acetylsalicylate]. AB - Lysine acetylsalicylate, a water-soluble salt of acetylsalicylic acid, administered intravenously to rabbits (15 and 100 mg/kg) and also in vitro (2-10 mg/ml) produced antiaggregational and anticoagulant effects pertaining to acetylsalicylic acid. Pharmacokinetics of acetylsalicylic acid injected intravenously to rabbits in the form of lysine acetylsalicylate is formalized by a biexponential equation for a two-compartment model. The main pharmacokinetic constants of acetylsalicylic acid in these experiments were found to be similar to those in humans. PMID- 3093271 TI - Hydrazone formation of 2,4-dinitrophenylhydrazine with pyrroloquinoline quinone in porcine kidney diamine oxidase. AB - Homogeneous diamine oxidase (EC 1.4.3.6) from porcine kidney was treated with the inhibitor 2,4-dinitrophenylhydrazine (DNPH). The coloured compounds formed were detached with pronase and purified to homogeneity. When the reaction with DNPH was conducted under an O2 atmosphere, the product (obtained in a yield of 55%) was the C(5)-hydrazone of pyrroloquinoline quinone (PQQ) and DNPH, as revealed by its chromatographic behaviour, absorption spectrum and 1H-NMR spectrum. Only 6% of this hydrazone was formed under air, the main product isolated being an unidentified reaction product of DNPH with the enzyme. Porcine kidney diamine oxidase is the second mammalian enzyme shown to have PQQ as its prosthetic group. In view of the requirements for hydrazone formation with DNPH, it is incorrect to assume that inhibition of this type of enzymes with common hydrazines is simply due to blocking of the carbonyl group of its cofactor. PMID- 3093270 TI - A novel mechanism of resistance to alpha-difluoromethylornithine induced by cycloheximide. Growth with abnormally low levels of putrescine and spermidine. AB - Treatment of the chemically transformed fibroblasts BP-A31 and other cell lines with low concentrations of cycloheximide (CHM) for 72 h followed by the removal of the protein synthesis inhibitor leads to the proliferation of alpha difluoromethylornithine (DFMO)-resistant phenotypes. These drug-resistant cells contain almost no ornithine decarboxylase (ODC) activity and concomitantly very low levels of putrescine and spermidine. Southern blot analysis and measurements of ODC activity and intracellular polyamine levels showed that the described mechanism of inducing resistance to DFMO triggered by CHM does not involve ODC gene amplification, altered transport of the drug or reduced affinity of the enzyme for DFMO. PMID- 3093272 TI - Enzymatic quantification of strand breaks of DNA induced by vacuum-UV radiation. AB - HindIII-digested plasmid DNA dried on an aluminum plate was irradiated by vacuum UV at 160 and 195 nm using a synchrotron irradiation system. A change induced in the DNA, presumably a single strand break, was quantified by the aid of the strand break-derived stimulation of poly(ADP-ribose) synthetase activity. The end group of strand breaks so induced was recognized by the enzyme as effectively as that by DNase I treatment, suggesting a nicking as the major lesion inflicted on the DNA. The fluence (UV) dependent stimulation of poly(ADP-ribose) synthetase activity was much higher upon 160 nm irradiation than upon 195 nm irradiation. PMID- 3093273 TI - Identification by molecular cloning of two forms of the alpha-subunit of the human liver stimulatory (GS) regulatory component of adenylyl cyclase. AB - Two DNA molecules complementary to human liver mRNA coding for the alpha-subunit of the stimulatory regulatory component Gs of adenylyl cyclase were cloned. One of the two forms is a full-length cDNA of 1614 nucleotides plus a poly(A) tail of 59 nucleotides. The deduced sequence of 394 amino acids encoded by its open reading frame is essentially identical to that of the alpha-subunits of Gs identified by molecular cloning from bovine adrenals, bovine brain and rat brain. Two independent clones of the other type of cDNA were isolated. Both were incomplete, beginning within the open reading frame coding for the alpha s polypeptide. One codes for amino acids 5 through 394 and the other for amino acids 48 through 394 of the above described cDNA of 1614 nucleotides, and both have the identical 3'-untranslated sequence. They differ from the first cDNA, however, in that they lack a stretch of 42 nucleotides (numbers 214 through 255) and have nucleotides 213 (G) and 256 (G) replaced with C and A, respectively. This results in a predicted amino acid composition of another alpha-subunit of Gs that is shorter by 14 amino acids and contains two substitutions (Asp for Glu and Ser for Gly) at the interface between the deletion and the unchanged sequence. We call the smaller subunit alpha s1 and the larger alpha s2. This is the first demonstration of a structural heterogeneity in alpha s subunits that is due to a difference in amino acid sequence. PMID- 3093274 TI - Mitogen treatment of permeabilized human T lymphocytes stimulates rapid tyrosine and serine phosphorylation of a 42 kDa protein. AB - Three agents which are mitogenic for T lymphocytes (phytohaemagglutinin, monoclonal antibody UCHT 1 and 12-O-tetradecanoylphorbol-13-acetate) stimulated rapid phosphorylation of a 42 kDa protein in permeabilized T lymphocytes. Phosphorylation occurred on tyrosine and serine residues. A non-mitogenic monoclonal antibody (RFT11) did not stimulate phosphorylation of this protein. Furthermore, the dose response of 42 kDa protein phosphorylation and of mitogenesis to increasing amounts of phytohaemagglutinin were closely similar. We therefore propose that mitogen-stimulated phosphorylation of the 42 kDa protein is part of the mechanism for transduction of mitogenic signals in lymphocytes. To our knowledge, this is the first report of rapid, ligand-stimulated tyrosine protein phosphorylation in T lymphocytes. PMID- 3093275 TI - Thrombin and IgE antigen induce formation of inositol phosphates by mouse E-mast cells. AB - Stimulation of murine chondroitin sulfate E containing mast cells (E-MC) in vitro either by thrombin or immunologically resulted in a rapid formation of inositol phosphates (IPs). Increase in all of the three IPs (IP1, IP2 and IP3) could be detected 20 s after stimulation. The depletion of Ca2+ from the medium resulted in more than 80% reduction in beta-hexosaminidase release from either thrombin or IgE antigen stimulated cells. However, both thrombin and IgE antigen increased the formation of IP3 under these conditions independent of the presence of extracellular Ca2+. PMID- 3093276 TI - Isolation and structure of the Streptococcus faecalis sex pheromone, cAM373. AB - The Streptococcus faecalis sex pheromone, cAM373, which induces a mating response of donor cells harboring plasmid pAM373 and is also produced by Staphylococcus aureus, was isolated and its structure determined. Supernatant from an overnight culture of a recipient strain was subjected to successive purification procedures, and 4.4 micrograms cAM373 was obtained. The isolated pheromone showed activity at a concentration as low as 5 X 10(-11) M. Sequence analysis indicated that cAM373 was a heptapeptide, H-Ala-Ile-Phe-Ile-Leu-Ala-Ser-OH, and that its Mr was 733. A synthetic replicate of the peptide showed the same biological activity and chromatographic behavior as the native cAM373. PMID- 3093277 TI - Ca2+ and phorbol ester synergistically induce HL-60 differentiation. AB - Exposure of HL-60 cells to subthreshold concentrations of TPA caused monocytic differentiation only when cells were cotreated with the Ca2+ ionophore A23187. Phorbol ester dose-response curves for growth arrest and enzymatic markers of differentiation were shifted to lower concentrations when the ionophore was present. Expression of a monocyte/granulocyte cell surface antigen also occurred only when cells were treated with both agents. Similar effects were seen with other active but not inactive phorbol esters and with another Ca2+ ionophore. The Ca2+ component of phosphoinositide-based signalling may thus play a role in HL-60 differentiation. PMID- 3093278 TI - Early modifications of gene expression induced in liver by azo-dye diet. AB - The expression and regulation of the phosphoenolpyruvate carboxykinase gene were not grossly modified by feeding rats a 3'-methyl-4-(dimethylamino)azobenzene containing diet despite maximum expression of the L-type pyruvate kinase gene being dramatically reduced as early as the 24th hour of the carcinogenic diet. Inhibition of aldolase B mRNA synthesis occurred more slowly, being maximum at the 3rd day. After stopping administration of the carcinogen, a very rapid, but transient increase of the L-type pyruvate kinase mRNA was observed at the 24th hour, whereas aldolase B mRNA increased only slowly. The amount of aldolase A mRNA fell quickly after termination of carcinogen administration, levels being normal at the 2nd-3rd day. At this time, the histological structure of the liver was indistinguishable from that of animals still receiving the azo-dye diet. It appears, therefore, that in the rat both administration and withdrawal of the azo dye carcinogen induce rapid modifications of the expression of some genes, before any cellular modification is distinguishable. PMID- 3093279 TI - Subunit structure of a cortical granule lectin involved in the block to polyspermy in Xenopus laevis eggs. AB - The cortical granule lectin of Xenopus laevis eggs is a large molecular mass glycoprotein involved in the post-fertilization block to polyspermy. We have investigated the subunit structure of this lectin and found that the native molecule contains 10-12 monomers, each of which has considerable charge and size heterogeneity due to glycosylated side chains. In addition, significant amino acid sequence homology is indicated by peptide mapping of subunits separated by isoelectric focusing. PMID- 3093280 TI - Differences in ovarian stimulation in human menopausal gonadotropin treated woman may be related to follicle-stimulating hormone accumulation. AB - Two groups of normal ovulatory women who displayed either a marked (high responders; HR) or a more subtle (low responders; LR) ovarian response to a fixed dose of human menopausal gonadotropins (hMG) were evaluated for differences in blood levels of hormones. Serum follicle-stimulating hormone (FSH) levels doubled during the first 3 days of treatment (to approximately 20 mIU/ml) in all patients; thereafter, the levels plateaued in LR but continued to rise steadily (to 35 mIU/ml) in HR. In the latter group, rise in estradiol (E2) and FSH was accompanied by an increase of luteinizing hormone (LH; two to five times) progesterone (P; four to eight times) testosterone (T; three to four times) and prolactin (PRL; 2 times) toward the end of the follicular phase. Positive correlation was found between FSH and E2 in HR and LR. Positive correlation was found, however, between LH, T, and P and between E2, P, and PRL only in HR. The extent of FSH accumulation in the circulation may be a principal factor in determining an individual's response to hMG therapy. Temporal changes of blood hormones indicated that the continuous rise in FSH levels in HR was associated with early luteinization of the follicles. Increased secretion of P in the follicular phase of these women (HR) probably synergized with the elevated E2 levels to elicit LH release. Similar changes in blood hormones were not found in LR. PMID- 3093281 TI - Changes in serum sex hormone-binding globulin, free estradiol, and testosterone during gonadotropin treatment. AB - Sex hormone-binding globulin (SHBG), estradiol (E2), percent free E2, percent of E2 bound to SHBG, and testosterone (T) were evaluated in 28 ovulatory women during human menopausal gonadotropin-stimulated cycles for in vitro fertilization. Patients were divided into two categories: low responders, in whom serum E2 concentration reached levels less than 1000 pg/ml (mean, 638 +/- 93), and high responders, with serum E2 levels greater than 1000 pg/ml (mean, 2219 +/- 330). A significant increase in SHBG can occur within a short time in high responders (from 62.8 to 103.9 nmol/l) but not in low responders. This increase is accompanied by a significant decrease in the percent free (bioavailable) E2, but the distribution of E2 between the fraction bound to SHBG or albumin did not vary. Despite the increase in the levels of SHBG, the concentration of bioavailable (free) E2 in hyperstimulated women is higher than in normal cycles. The significant increase in T in high responders, by virtue of its higher affinity for SHBG, probably contributes to the increased levels of bioavailable E2. PMID- 3093282 TI - Influence of weight in the induction of ovulation with human menopausal gonadotropin and human chorionic gonadotropin. AB - Patients failing to ovulate and conceive on clomiphene citrate (CC) or CC plus human chorionic gonadotropin (hCG) or patients with pituitary gonadotropin deficiency are candidates for human menopausal gonadotropin (hMG) plus hCG therapy. The duration and number of ampules needed to stimulate ovarian response leading to ovulation and/or pregnancy vary individually. Seventy-one patients who had complete follow-up evaluation and accurately documented body weights at the time of therapy were considered for the study. Of these 71 patients, 41 (57.3%) conceived in 293 cycles. The average number of ampules of hMG used by patients with 10% to 20% below ideal body weight (IBW) was 13.9 +/- 6.3 (mean +/- standard deviation [SD]). The average number of ampules used by patients with normal +/- 10% IBW was 14.2 +/- 3.5. Patients who were overweight by 10% to 25% used 15.3 +/ 5.4 ampules, and patients overweight by greater than or equal to 25% used 20.9 +/- 5.6 ampules of hMG. Eleven patients with severe hypothalamic chronic anovulation needed an average of 20.6 +/- 6.2 ampules. The data reveal a direct relationship between IBW and the amount of hMG needed to induce ovulation and/or pregnancy; however, in the presence of chronic hypoestrogenic conditions, it is expected that these patients will need higher amounts of hMG, regardless of body weight. PMID- 3093283 TI - Clinical investigation of a low-dose levonorgestrel-releasing vaginal ring. AB - Contraceptive effectiveness and adverse effects were observed in 108 women who used the levonorgestrel-releasing vaginal ring. One-year cumulative net rates per 100 women were pregnancy, 3.7; expulsion, 4.6; use-related discontinuation, 26.9; and continuation, 71.2. The main adverse effects were menstrual disturbances, which improved after longer usage. The menstrual blood loss (MBL), hemoglobin (Hb), and ferritin concentrations were determined in 20 women. The MBL gradually declined after insertion of the vaginal ring and the Hb concentration was significantly increased in the 6th and 12th periods after insertion (P less than 0.05). PMID- 3093285 TI - [Reactivity of cerebral vessels: physiologic basis, informational significance, criteria for evaluation]. PMID- 3093284 TI - Induction of fertility in a man with hypogonadotropic hypogonadism with very low seminal volume. AB - Pituitary function studies were performed on a 31-year-old man who had oligospermia and a very low seminal volume (0.1 ml). The low testosterone and gonadotropin levels, the remarkable testosterone response to human chorionic gonadotropin (hCG) stimulation, and the sluggish luteinizing hormone (LH) response to luteinizing hormone stimulating hormone (LH-RH) stimulation suggested the presence of hypogonadotropic hypogonadism. Treatment with a combination of human menopausal gonadotropin (hMG)-hCG resulted in the increase in the volume of seminal fluid and the sperm density. His wife achieved two pregnancies during the treatment. This report indicates that the findings of oligospermia and very low seminal volume should be followed by an investigation of the hypothalamo pituitary testicular axis. Fertility in men with hypogonadotropic hypogonadism can be effectively induced with a combination of hMG-hCG treatment. PMID- 3093286 TI - [Intraventricular administration of 6-hydroxydopamine and ascorbic acid changes 3H-GABA absorption by synaptic endings of the cerebral cortex of the rat]. AB - Combined administration of 6-hydroxydopamine with ascorbic acid had no effect on 3H-GABA uptake in the rat cortical synaptosomes, whereas a significant increase of the latter was observed within 2 days after 6-hydroxydopamine alone. Ascorbic acid alone (20 micrograms in 20 microliter saline, bilaterally) significantly increased 3H-GABA uptake within 2 days and decreased it within 21 days. The data suggest that: catecholaminergic system may affect (directly or indirectly) cortical GABAergic neurons, and injection of ascorbic acid into lateral ventricles exerts an obvious effect on synaptosomal 3H-GABA uptake in the brain cortex. PMID- 3093287 TI - [Contractile function of the smooth muscle of the superficial arteries of the cerebral cortex]. AB - Cerebral vessel's muscle cells responses to biologically active substances and the metabolic factors were found to depend on the initial functional level of smooth muscles in segments of the cow pial artery. PMID- 3093288 TI - [Oxygen transport properties of the blood in experimental renal hypertension in the rat]. AB - In rats with artificial renal hypertension, the amount of erythrocytes in the blood was increased in 43% of cases within 2-3 months after surgery. Diverse changes of the blood oxygen-transport properties indicate several mechanisms of the organism adaptation to changes in oxygen regiment in response to the arterial pressure increase due to ischemia of renal tissue: an increase in the blood oxygen capacity; changes of the hemoglobin oxygen-binding properties. The parameters under study, except the arterial pressure, did not differ from the control ones in a number of experimental animals. PMID- 3093289 TI - [Role of the pituitary in mechanisms of hypothalamic regulation of the activity of the cardiovascular and digestive systems]. PMID- 3093290 TI - Costing out nursing services. PMID- 3093291 TI - The HLA class II antigens determined by cellular techniques. A review. AB - The D region of the HLA system is very complex. Three loci, HLA-DR, DQ and DP, are now very well established. However, the question of the independence of the first known locus of this region remains elusive--it is not yet known if HLA-D antigens are really independent or if they represent some epitopes on the molecules of HLA-DR/DQ antigens. The HLA-DP antigens represent an independent series in the HLA system recognized by the PLT technique. On the other hand, the HLA-PL antigens also detected by PLT correlate with both HLA-D and HLA-DR antigens, and it seems that they do not constitute an independent group of HLA antigens. PMID- 3093292 TI - [Inhibitory effect of prolactin secretion by luteinizing hormone releasing hormone agonist (buserelin)]. AB - The LH RH agonist Buserelin was continuously administered through the nose over an extended period to 5 patients with endometriosis at daily doses ranging between 300 micrograms and 1,200 micrograms. The clinical findings and endocrinological dynamics, with emphasis on PRL secretion function, were investigated and the findings below were obtained. The clinical findings showed Buserelin to be effective against endometriosis. The administration of Buserelin markedly inhibited the secretion of LH and FSH under LH-RH loading. The administration of Buserelin markedly inhibited the secretion of PRL and the degree of inhibition appeared to be dependent on the dose and duration of Buserelin administration. No correlation between E2 and PRL was observed during Buserelin administration. The findings suggest that Buserelin inhibits PRL secretion by direct CNS activity, not indirectly through inhibition of E2 production. PMID- 3093293 TI - [Antibiotic susceptibility of Neisseria gonorrhoeae strains in the Dresden area 1983/84]. PMID- 3093294 TI - Species-dependent differences of the biochemical properties of diamine oxidase. AB - Diamine oxidase (DAO) from tissues of mice, rats and humans showed different properties with respect to stability and kinetic parameters. DAO-activities in homogenates of rat or human tissues, but not of mouse tissues, rapidly decreased upon storage at -20 degrees C. The Km-value for putrescine was 90 microM in mouse kidney or intestine. In rats different Km-values were observed before (272 microM) and after freezing (102 microM). A similar effect was observed with DAO in human kidney (321 and 39 microM, respectively). Treatment of rats with heparin resulted in a depletion of intestinal DAO and the concomitant appearance of DAO in blood. The enzyme remaining in the intestine showed the lower Km-value. PMID- 3093295 TI - Long-term treatment of angina pectoris with carteolol: a new beta-adrenergic receptor blocking agent. AB - Seventy-two patients entered the treatment phase of an open, long-term, dose ranging trial of carteolol in stable, exercise-induced angina pectoris. Patients were to be treated with progressive doses of carteolol (2.5, 5, 10, 20, 40, and 60 mg), given as a single daily oral dose. Thirty of the patients (42%) completed one year of treatment with carteolol as the sole antianginal therapy. The most frequent final carteolol doses were 20 mg and 40 mg once daily. Statistically significant improvements from baseline in exercise tolerance as reflected in time to onset of angina, time to the endpoint of exercise and time to the onset of 1 mm S-T segment change on ECG were observed in carteolol-treated patients. Exercise-induced increases in heart rate and double-product were significantly suppressed, compared to baseline, throughout the study. Resting heart rate and double-product were modestly decreased. Carteolol was shown to be effective and safe when administered on a long-term basis to patients with angina pectoris. PMID- 3093296 TI - A specific nuclear protein and poly(ADPribose)transferase activity in lizard oviduct during the reproductive cycle. AB - A specific nuclear protein (SNP) appears in the oviduct of the lizard, Podarcis s. sicula Raf., during the recovery phase of the breeding cycle. The protein has a low molecular weight (9.9 kDa), a high electrophoretic mobility and a peculiar amino acid composition. It seems to be regulated by estradiol which, in this species, is involved in oviduct stimulation. Nuclear poly(ADPribose)transferase activity increases in the oviduct as the organ grows, and it peaks upon morphological maturation. Thereafter, as the oviduct becomes secretory, the enzyme returns to basal level. A transient increase of poly(ADPribose)transferase precedes the appearance of SNP, which suggests that the two phenomena are related. PMID- 3093297 TI - Mouse sperm antigens that participate in fertilization. IV. A monoclonal antibody prevents zona penetration by inhibition of the acrosome reaction. AB - To investigate the molecular basis of gamete interaction in mammals, monoclonal antibodies (mAbs) have been generated by syngeneic immunization with mouse testis. Previous work has described two particular mAbs, M41 and M42, which localize indistinguishably to the plasma membrane overlying a restricted portion of the acrosome, but recognize different antigens. One of the mAbs, M42, inhibits mouse fertilization in vitro significantly, but only in the presence of the zona pellucida, whereas M41 has no apparent effect upon any assayable event in the fertilization process. The experiments described here were performed to identify the precise event of sperm-zona interaction (sperm-zona binding, induction of the acrosome reaction, or penetration through the zona) that is affected by M42 mAb. Capacitated mouse sperm binding to the zona pellucida was undiminished following pretreatment with M42 mAb, when compared to levels achieved using either no mAb- or to M41 mAb-treated control sperm. When the effect of mAbs on the zona-induced AR was examined, the percentage of acrosome reacted (AR) sperm at the zona surface increased with time, plateauing at approximately 90 min post insemination, with 78% of the bound cells AR in the control and the M41 mAb treated groups. M42-treated sperm never achieved greater than 23% AR cells over the 120-min interval assayed. To quantitate this effect, capacitated sperm were exposed to increasing concentrations of acid-solubilized zonae. Increased proportions of AR sperm were found in the control and M41 mAb-treated groups, up to a maximum of 70-76% AR cells with 8 or 12 zonae/microliter. In contrast, M42 treated sperm displayed only 21-28% AR cells over the entire range of zonae concentrations tested. An entirely different result emerged when acrosome reactions were induced with A23187: M42 was no longer able to prevent the AR. This ability of A23187 to override M42 mAb's inhibitory effect on the AR permitted specific examination of the possible effect of M42 mAb on sperm penetration through the zona pellucida. In the presence of A23187, zona penetration levels for M42 mAb-treated sperm were equivalent, both qualitatively and quantitatively, to control and to M41 mAb-treated sperm under the same conditions. It appears, therefore, that M42 mAb identifies a high molecular weight doublet (220-240 kDa) of mouse sperm that participates specifically in the induction of the sperm's acrosome reaction as it occurs under physiological conditions. PMID- 3093298 TI - Ommatidial development in Drosophila eye disc fragments. AB - We have tested the hypothesis that the leading edge of the growing Drosophila compound eye acts as a template that organizes unpatterned cells of the retinal epithelium into the accurate cellular mosaic of the eye. Unpatterned fragments of the epithelium, not containing the leading edge of the growing field, were transplanted into larval hosts. After hosts pupated, the implants were recovered; most contained ommatidia, demonstrating that the leading edge of the growing eye pattern is not required for its propagation. In a second set of experiments, implants were recovered before hosts pupated and examined for ommatidia using a monoclonal antibody. These implants likewise differentiated ommatidia and the temporal progress of retinal development in the implants mirrored that of normal development. A schedule of ommatidial development thus appears to be mapped onto the retinal epithelium in advance of the leading edge. PMID- 3093299 TI - High motivation toward food increases food-sharing in cotton-top tamarins. AB - In order to explore whether or not adult motivation influences transfer of food to infants in cotton-top tamarins (Saguinus oedipus oedipus), 2 experiments were carried out with 3 large captive family groups. Examination of (a) natural changes in food motivation during feeding, and (b) elevated motivation toward food by giving highly preferred items, showed that the adult monkeys shared food more when their own level of motivation was high. This suggests that food transfer is not merely a consequence of adult satiation, but that matching sharing with high adult motivation is a mechanism which ensures that infants receive ample food, the best items, and also rare items of high quality. PMID- 3093300 TI - Interferon-mediated induction of Ia antigen expression on isolated murine whole islets and dispersed islet cells. AB - Islets from male B10.BR mice (H-2k) were isolated by the collagenase technique, handpicked with a Pasteur pipette, and incubated (either intact or after dispersion with Dispase) for 0, 3, 5, 7, 10, or 14 days in tissue culture medium supplemented with either lymphokine supernatants or recombinant murine interferon gamma. Islets and single cells were examined for IAk molecules by use of indirect immunofluorescence. Ia-positive islet cells were identified on the surface of islets incubated with 5-10% lymphokine for greater than 4 days or with 10, 100, or 1000 ng/ml interferon for greater than 6 days. Islets incubated in unsupplemented medium were Ia negative. Incubation with 5% lymphokine induced Ia expression on 10-40% dispersed islet cells cultured for greater than 9 days. Dual immunofluorescent staining for Ia and insulin revealed that Ia-positive cells included both beta- and non-beta-cells. PMID- 3093302 TI - Effect of aldose reductase inhibitor (sorbinil) on integration of polyol pathway, pentose phosphate pathway, and glycolytic route in diabetic rat lens. AB - This study examines the effect of an aldose reductase inhibitor (sorbinil) on the flux of specifically labeled glucose through alternative pathways of metabolism in the lens of normal and diabetic rats 1 wk after the induction of diabetes with alloxan. In the diabetic rat lens, there was an apparent increase in the flux of glucose through the pentose phosphate pathway (PPP), as measured by the difference in the yields of 14CO2 from [1-14C]glucose and [6-14C]glucose [C1-C6], this value was 0.087 +/- 0.005 and 0.263 +/- 0.034 mumol X g lens-1 X h (mean + SE of 6 values) for control and diabetic rats, respectively; sorbinil treatment decreased the values to 0.065 +/- 0.008 and 0.171 +/- 0.028, respectively. With glucose tritiated on carbon 2 or 3, it has been shown that the flux of glucose through the polyol route is increased, whereas the flux through the glycolytic pathway is decreased in the diabetic rat lens; both are restored toward normal in the sorbinil-treated diabetic group. These results suggest that the dual effects of diabetes in increasing the lens content of glucose and glucose 6-phosphate and the flux of glucose in the polyol pathway will result in an increased utilization of NADPH and production of NADH, factors favoring the flow of glucose through the PPP and restricting the glycolytic route in the diabetic rat lens. The inhibition of aldose reductase by sorbinil tends to normalize the redox state of the nicotinamide nucleotides, reimposing the NADPH limitation on the PPP and increasing the availability of NAD+ for the glycolytic route. PMID- 3093301 TI - Hormone release, islet yield, and transplantation of fetal and neonatal rat dorsal and ventral pancreatic islets. AB - Fetal (20-21 day gestation) and neonatal (less than 5-day-old) rat islets were isolated from the glucagon-rich (dorsal) and glucagon-poor (ventral) pancreatic regions. After 1 or 2 wk in culture, groups of islets from each region were transferred to culture dishes containing Krebs-Ringer bicarbonate buffer with low (2.4 mM) and high (16.7 mM) glucose plus aminophylline. After 2 wk in culture, insulin released into medium was higher than after 1 wk, and more so if the islets originated from dorsal tissue (P less than .01). Glucagon release in response to alanine (10 mM) stimulation was also significantly higher in dorsal than in ventral islets (6.38 +/- 1.98 vs. 1.49 +/- 0.89 pg X islet-1 X h-1, respectively; P less than .02). Coincident with higher insulin and glucagon release, islet yield was greater in tissue from the dorsal neonatal pancreas than from that obtained in the fetal and neonatal ventral pancreas [range: dorsal, 131 180 (median, 153), vs. ventral, 53-127 (median, 84), islets obtained on day 5 of culture]. Neonatal islets of dorsal origin were transplanted intrasplenically (500-3000 islets) to streptozocin-induced diabetic inbred Lewis rats. Only rats receiving greater than 2500 islets were cured by transplantation. These experiments show that dorsal fetal islets secrete more insulin than do ventral islets and that islet yield is higher when islets are isolated from dorsal rather than from ventral perinatal pancreatic tissue. Despite their in vitro behavior, more neonatal dorsal islets are required to cure experimental diabetes than are reported with adult islets. PMID- 3093303 TI - [Acid-base status and the blood gas composition of inhabitants of northeastern USSR]. PMID- 3093304 TI - [Acute epidemic non-A, non-B hepatitis: clinical study of 38 cases seen in Chad]. AB - An epidemic of acute non-A, non-B hepatitis (NANBH), observed in 38 young French soldiers in Chad, presumed to be waterborne, allowed to describe the clinical picture of the disease. The main features of this entity were compared with those observed during previously described outbreaks of waterborne NANBH encountered in North Africa and in Asia as well as with 85 cases of viral type A hepatitis of various other geographical origins, observed during the same period of time. Similarities between the clinical features of the disease within every water transmitted NANBH epidemic center were suggestive of a particular nosologic entity among the non-parenterally transmitted cases of NANBH. In young male subjects, the course of the disease proved to be milder than that of type A viral hepatitis. A 5 ml dose of non-specific French-prepared human immunoglobulins had no prophylactic effects on the disease. PMID- 3093305 TI - Chronic antral gastritis in duodenal ulcer. Natural history and treatment with prostaglandin E1. AB - The natural history of chronic antral gastritis in relation to the healing of duodenal ulcer and its response to treatment, if any, are unknown. We performed a double-blind controlled trial using an oral prostaglandin E1, misoprostol, in 229 patients with active duodenal ulcer randomized to receive placebo (n = 76), misoprostol 200 micrograms (n = 77), or misoprostol 300 micrograms (n = 76), q.i.d. orally. Healing of duodenal ulcer was assessed biweekly up to 12 wk by endoscopy, during which procedures at least two antral and two fundal biopsy specimens were taken. The activity and the degree of chronic inflammation of gastritis, as assessed histologically by the infiltration of polymorphs and chronic inflammatory cells, respectively, was graded blindly by two pathologists as nil, mild, moderate, or severe. Before treatment, 99% of patients had chronic antral gastritis and 1.5% had chronic fundal gastritis. In the placebo group, healed duodenal ulcer was associated with significantly (p less than 0.01, life table analysis) higher incidence of improvement of the activity of the antral gastritis (nil or mild as endpoint) than unhealed ulcer (30% vs. 4% at week 8). Irrespective of whether duodenal ulcer was healed or unhealed, significantly (p less than 0.01) more patients on misoprostol (50% at week 8) showed improvement (nil or mild as endpoint) than the placebo group. The degree of chronic inflammation of the antral gastritis showed similar significant changes in favor of misoprostol. Smoking and alcohol intake had no significant effect on the improvement of chronic antral gastritis. In conclusion, healing of duodenal ulcer was associated with improvement of the activity of chronic antral gastritis, which, as shown for the first time, could be further enhanced by a therapeutic agent--prostaglandin E1. PMID- 3093306 TI - Anorectal ergotism: another cause of solitary rectal ulcers. AB - Anorectal ulceration was observed in 6 patients who excessively used suppositories containing ergotamine tartrate. The mucosal lesions of the rectum resembled those observed in the "solitary rectal ulcer syndrome." However, characteristic features of ergotamine-induced ulcers are absence of a mucosal prolapse, lack of a history of constipation, and rapid healing after discontinuation of the drug. Furthermore, the rectal lesion may be associated with anal ulceration, which occasionally presents as the only clinical manifestation of "anorectal ergotism." PMID- 3093308 TI - [Significance of the urethral pressure profile in the diagnosis of urethral diverticulum]. AB - Diverticulum of the urethra was diagnosed by us in ten women during the past two years. In nine of these, the urethral pressure profile showed a characteristic course: In the region of the diverticulum--confirmed subsequently by radiography- a drop in pressure was recorded as a sign of damage to the wall. The value and importance of the individual steps in the diagnosis of diverticula are discussed. Suspicion of a diverticulum in the urethra can be raised by careful anamnesis and by means of the urethral pressure profile. This suspicion can be safely confirmed or refuted via urethrography using the double-balloon catheter. PMID- 3093307 TI - [Inhibition of ovulation with 35 micrograms of ethinyl estradiol and 2 mg of cyproterone acetate (Diane 35)]. AB - In the study reported here the ovulation inhibition dose for cyproterone acetate was determined. Experiments showed that the ovulation inhibition dose is 1 mg of cyproterone acetate, administered daily. Results proved that the cyproterone acetate dose cannot be reduced when cyproterone acetate is combined with ethinyl estradiol. However, the objective of this study was to determine whether it is possible to reduce the estrogen dose to 35 micrograms when the common combination of 2 mg cyproterone acetate and ethinyl estradiol is being used. After a control menstruation cycle, 2 mg cyproterone acetate and 35 micrograms ethinyl estradiol were administered daily to six women with normal menstruation. Drug administration began on Day 5 and ended on Day 25. During the control cycle, the first treatment cycle, and the third treatment cycle, LH, FSH, 17 beta estradiol, progesterone, testosterone, prolactin, and SHGB were examined daily. Cervix score and karyopyknosis index were determined at the same time. In addition, antithrombin III was examined during the control cycle and during the third treatment cycle. Present results show that ovulation inhibition is possible with dose reduction of ethinyl estradiol to 35 micrograms, combined with 2 mg of cyproterone acetate. Increase in SHBG and reduction in testosterone serum level point to an additional antiandrogenic effect of cyproterone acetate, aside from its cellular effect. The combined preparation discussed here does not bring about any changes in antithrombin III values. Results permit the conclusion that ovulation inhibition is insured with a reduction of the daily estrogen dose from 50 micrograms to 35 micrograms. PMID- 3093309 TI - [Lupus anticoagulant in pregnancy]. AB - The case of a patient with recurrent abortions and one premature deficient birth is described. The underlying condition was an immunocoagulopathy caused by a lupus anticoagulant, leading to a tendency to thrombosis and in pregnancy to abortions, stillbirths, and deficient births. The diagnostic and therapeutic procedure is described and discussed. PMID- 3093310 TI - [Diagnosis of holoprosencephaly with cyclopia in the fetus]. AB - The typical ultrasound findings in cases of fetal holoprosencephaly with hypotelorism and cyclopia are explained with reference to a case history. Hypotelorism was confirmed by measurement of the distance between the orbits of the fetus. PMID- 3093311 TI - [Initial results in the treatment of endometriosis with the LH-RH analog buserelin]. AB - Twenty-six women, most of them with advanced endometriosis (Stage III according to Acosta), were treated for six months with the LH-RH agonist Buserelin. After initially increased liberation both of the gonadotropins as well as of the sexual steroids there was consecutive inhibition of gonadal function, especially after inhibition of FSH secretion. Within two to four weeks estradiol production was completely and lastingly suppressed in 21 of the 26 women. In three women it lasted for three months and in two women estradiol again rose up to three times during the period of observation. Correspondingly, 22 of the women suffered from hot flushes as early as within the first two months. Twenty of the 26 women became completely free of symptoms within four to six weeks, and a clear regression of the pain was recorded in another four. In two women the complaints persisted without change. Withdrawal bleeding of short duration occurred simultaneously with the intermittent increases in estradiol levels; however, this bleeding usually caused little or no pain. Eleven of the 19 endometrium biopsies performed during therapy revealed a dormant endometrium, and only in one case was proliferated endomedium found, in the third month of treatment, in a stage of transition to hyperplasia. The remaining seven biopsies were insufficient for assessment. In seven women with advanced endometriosis, laparotomies were performed after drug treatment. Histologic study of the endometriosis tissue thus obtained revealed, except in the two nonresponders, cicatrized tissue with atrophic glands and severely reduced stroma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093312 TI - [The fibronectin level in the cryoprecipitate and in the blood of patients with hemophilia]. PMID- 3093313 TI - Anti-thrombotic effect of KC-404, a novel cerebral vasodilator. AB - KC-404 prevented mice from death and rats from A-V block, both induced by rapid i.v. injection of adenosine diphosphate (ADP), at high doses (5-100 mg/kg, i.v.). KC-404, at relatively lower doses (0.5-2 mg/kg, i.v.), inhibited the electroencephalographic (EEG) change in rat rapidly administered with arachidonic acid (AA) into the internal carotid artery. KC-404 (0.3-3 mg/kg, p.o.) inhibited the necrotic change of lower leg, paw or finger of rat when injected with sodium laurate into the femoral artery. KC-404 at doses up to 100 mg/kg, p.o. did not alter bleeding time in rat. Thus, KC-404 is expected to be of therapeutic value in cerebrovascular disorders accompanying thrombus in cerebral vasculature. PMID- 3093314 TI - Effect of nicotine on prostacyclin formation in human endocardium in vitro. AB - The effect of nicotine on the formation of prostacyclin by human endocardium was studied in vitro. Slices of cardiac valve cusps were incubated in a saline medium and the prostacyclin-like activity generated spontaneously by the tissue specimens was assessed in terms of its capacity to inhibit ex vivo platelet aggregation. In separate experiments supernatants of valvular tissue homogenates were incubated with [14C]arachidonate. This resulted in the appearance of labelled 6-keto-prostaglandin F1 alpha in the radiochromatograms, indicating the formation of prostacyclin in the homogenates. Nicotine inhibited dose-dependently the spontaneous generation of prostacyclin-like activity (I50 approximately equal to 2 X 10(-4) M), as well as the formation of 6-keto-prostaglandin F1 alpha (I50 approximately equal to 2 X 10(-5) M), indicating an inhibitory effect of the drug on endocardial prostacyclin production. PMID- 3093315 TI - Blood-retinal barrier permeability to carboxyfluorescein and fluorescein in monkeys. AB - Lipid solubility is a major determinant of permeability across the blood-brain barrier, to which the blood-retinal barrier (BRB) has many similarities. Carboxyfluorescein is a dye with about 1/1000 the lipid solubility of fluorescein, but their molecular sizes and spectral characteristics are similar. We studied the importance of lipid solubility in BRB permeability by comparing the BRB permeabilities to these two dyes. Dye in the vitreous and plasma of four monkeys was measured by fluorophotometry. The estimated inward permeability coefficients (Pin) were 11 +/- 7.4 X 10(-6) cm/min (mean and SD) for carboxyfluorescein and 21 +/- 5.9 X 10(-6) cm/min for fluorescein. The ratio of the means was 1/1.9, far from the expected 1/1000. This finding suggests that the BRB does not function as a continuous lipid membrane and that other factors are more important determinants of permeability for these dyes than lipid solubility. PMID- 3093316 TI - [Data on the hygienic regulation of pentachloroacetophenone in water]. PMID- 3093318 TI - Chronic myeloid leukemia. PMID- 3093317 TI - Effect of enprostil, a synthetic prostaglandin E2 on 24 hour intragastric acidity, nocturnal acid and pepsin secretion. AB - We have studied the effect of a prostaglandin E2 analogue (enprostil), on intragastric acidity, gastric acid and pepsin outputs during a 24 hour period in nine patients with duodenal ulcer in remission. Enprostil 35 micrograms bd dose inhibited 24 hour intragastric acidity by 38% and a 70 micrograms nocturnal dose by 33%. Decrease in nocturnal pepsin secretion was both volume and concentration related. PMID- 3093319 TI - Structure and "in vitro" functions of platelets stored as platelet concentrates at room temperature. PMID- 3093320 TI - Cytochemical characterization of acute lymphoblastic leukemia. PMID- 3093321 TI - Hematological findings in adult T-cell lymphoma by cytofluorographic analysis. Correlation with histopathology, ultrastructure and immunohistochemistry in 4 cases. PMID- 3093322 TI - "Normal" values in hemorrheology. PMID- 3093323 TI - Pulmonary aspergillosis complicating aplastic phase in hematologic patients. PMID- 3093324 TI - Prognosis and management of patients affected by multi pre-treated Hodgkin's disease. PMID- 3093325 TI - Therapy-related ovarian dysfunction in women treated for Hodgkin's disease. PMID- 3093326 TI - Philadelphia (Ph), 14q+ and 1q+ chromosomes in immunoblastic phase (Richter's syndrome) in a patient with T chronic lymphocytic leukaemia. PMID- 3093327 TI - Generalized sarcoid-type reaction associated with non-Hodgkin's lymphoma. PMID- 3093328 TI - Non Hodgkin lymphoma localized in the liver: report of a case without involvement of the other tested districts. PMID- 3093329 TI - Monoclonal immunoglobulins associated with myeloproliferative disorders. PMID- 3093330 TI - Lymphoproliferative disease in primary B-cell immunodeficiency. Lymphoplasmocytoid lymphoma or Sjogren's pseudo-lymphoma? PMID- 3093331 TI - The possible role of blood platelets in tumour growth and dissemination. PMID- 3093333 TI - Pitfalls in blood sampling. Influence of posture and venous occlusion time. PMID- 3093332 TI - In vitro active cyclophosphamide derivatives in cleansing procedures intended for autologous bone marrow transplantation. PMID- 3093334 TI - Beta-glucuronidase of neutrophils in psoriasis. PMID- 3093335 TI - Effect of plasma protease inhibitors on tumor cell-induced platelet aggregation. PMID- 3093336 TI - Role of accessory components in the activation of vitamin K-dependent coagulation factors. AB - Kinetic studies of prothrombin activation and intrinsic factor X activation carried out in the absence and presence of phospholipids and the protein cofactors Va or VIIIa have provided insight in the mechanism by which the accessory components enhance coagulation factor activation. In intrinsic factor X and prothrombin activation, phospholipids cause a drastic drop of Km for the substrates factor X and prothrombin, whereas the protein cofactors factor Va and factor VIIIa increase Vmax of the prothrombin- and factor X-activating reactions. The mode of action of factor Va in prothrombin activation is however somewhat more complex. Besides its stimulatory effect on the catalytic activity of factor Xa, Factor Va also plays an important role in the assembly of the prothrombin activating complex at phospholipid surfaces especially when the latter have a low affinity for vitamin-K-dependent coagulation factors. This effect is likely accomplished by promoting the binding of both prothrombin and factor Xa to the procoagulant surface. PMID- 3093337 TI - Transfusion of Rh-incompatible blood components to cancer patients. AB - To study the effects of Rh0D incompatible transfusion of platelets and/or granulocyte concentrates, we analyzed the transfusion history of 118 oncology patients. Patients received a mean 36.2 units of random platelets, a mean 6.2 concentrates of single donor platelets, and a mean 8.4 concentrates of granulocytes. Patients were not treated with anti-Rh0D specific immunoglobulin following the incompatible transfusions. The patients were followed for a mean 9.4 months to detect the appearance of Rh0D antibodies. Of the 118 patients, 3 were lost to follow-up. Of the remaining 115, 2 cases (1.74%) developed anti-Rh0D following administration of the incompatible transfusions. PMID- 3093338 TI - [Electrophysiological effects of bunaftine, an antiarrhythmic drug, on action potential characteristics in ventricular muscle preparations]. AB - The electrophysiological effects of bunaftine were studied using the glass microelectrode technique. Bunaftine at 1, 5 and 10 mg/l produced a concentration dependent depression of the maximum rate of rise of the action potential in guinea pig papillary muscle preparations without affecting the resting membrane potential and the action potential amplitude. The action potential duration (APD50, APD90) was significantly prolonged by the treatment with 1 and 5 mg/l bunaftine, while it was not changed by the treatment with 10 mg/l. The absolute refractory period (ARP) was also prolonged dose-dependently by the treatment of bunaftine; It was excessively prolonged (177% of control) at the concentration of 10 mg/l. Disopyramide produced similar electrophysiological changes to those of bunaftine except for the prolongation of ARP. ARP/APD90 ratio was significantly increased by bunaftine, but not by disopyramide. These electrophysiological effects of bunaftine and disopyramide observed in guinea pig ventricular preparations were similarly found in canine ventricular muscle preparations. These results indicate that the electrophysiological characteristics of bunaftine are similar to those of disopyramide in that the most prominent effect was the prolongation of ARP. PMID- 3093339 TI - [Study of the ameliorating effects of an enteral nutrient for liver failure on hepatic encephalopathy: effects of SF-1008C on plasma and brain free amino acids, intracerebral amine concentrations and electroencephalogram in portacaval shunted rats with ammonia loading]. AB - The ameliorating effects of an enteral nutrient for liver failure (SF-1008C), which is enriched with branched-chain amino acids (BCAA) and includes few aromatic amino acids (AAA), were investigated. The blood ammonia, plasma and brain free amino acids, intracerebral amine concentrations and electroencephalogram were measured in portacaval shunted rats with 10% ammonium acetate (3 ml/kg, i.p.) (PCS) as a model of hepatic encephalopathy. The blood ammonia and plasma free amino acid concentrations in PCS rats were significantly increased in comparison to sham-operated (Sham) rats. Thus, the plasma BCAA/AAA ratio in PCS rats was appreciably reduced. Concomitant with the abnormal plasma amino acid concentrations, the brain free amino acid concentrations in PCS rats were markedly increased in comparison to the Sham rats. Moreover, the intracerebral tryptophan (Trp) and 5-hydroxyindol acetic acid (5-HIAA) concentrations were significantly increased, and the intracerebral dopamine (DA) concentration was significantly decreased in the PCS rats. The intracerebral serotonin (5-HT) and norepinephrine (NE) concentrations were, however, hardly changed. A smaller voltage for the electroencephalogram was used in the PCS rats than in the Sham rats. Abnormal plasma and brain free amino acid concentrations in PCS rats were normalized by oral administration of SF-1008C, and the low voltage electroencephalograms in the PCS rats were suppressed. On the other hand, abnormal plasma and brain free amino acid concentrations in the PCS rats were hardly normalized by oral administration of ED-AC, an elemental diet based on an amino acid composition of egg protein. These results suggest that SF-1008C affects brain free amino acids, intracerebral amine concentrations and electroencephalogram by ameliorating abnormal plasma free amino acid concentrations. Moreover, there is a highly significant correlation between the plasma BCAA/AAA ratio and the brain BCAA/AAA ratio, and this finding suggests that the plasma free amino acid patterns reflect the brain free amino acid patterns. PMID- 3093340 TI - Relationship between sporulation and synthesis of mycobacillin and dipicolinic acid under condition of catabolite repression in Bacillus subtilis. AB - Sporulation was repressed in the parent strain by various carbon sources whereas glucose-resistant mutants were resistant to them but not to glycerol 2-phosphate. Both mycobacillin and dipicolinic acid synthesis were repressed in the parent by some of the compounds tested, viz. glucose, pyruvate and glycerol 2-phosphate. However, these syntheses in the glucose-resistant mutants were not repressed by glucose and pyruvate but were repressed by glycerol 2-phosphate. The possible interrelationship between sporulation, dipicolinic acid and mycobacillin synthesis is discussed in light of these findings. PMID- 3093341 TI - Pyocyanin preparation from Pseudomonas aeruginosa isolated from heterogeneous clinical materials. AB - Pure pyocyanin was prepared from 120 strains of Pseudomonas aeruginosa isolated from different clinical specimens. The modified method used increased the purification 425-fold. The spectra of pyocyanin of all strains were found to be identical with a single major peak at 363 nm. The only difference between these spectra appeared to be the level value absorbance. Strains recovered from different clinical specimens differ in their ability for pigment production. The strains isolated from urine produced higher amounts of pyocyanin than other isolates. PMID- 3093342 TI - [Dysregulation in stem cell proliferation. Detection in a patient with erythroblasto- and reticulocytopenia]. PMID- 3093343 TI - [Principles of therapy with fibrinolytic agents]. PMID- 3093344 TI - [Fibrinolytic treatment of acute myocardial infarct]. PMID- 3093345 TI - [Vasodilator therapy in pulmonary hypertension and chronic obstructive lung disease (COPD). Hemodynamic studies exemplified by nifedipine and nitroglycerin]. AB - In 41 patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension, the effects of sublingual administration of 20 mg nifedipine and 0.8 mg nitroglycerin on the hemodynamics were assessed at rest and during bicycle ergometry. Additionally, in six patients, the effects of nifedipine during longterm treatment were analyzed. On acute testing, at rest and during exercise nifedipine led to decreases in mean pulmonary artery pressure of 16% and 23% and pulmonary arteriolar resistance of 23 and 35%, respectively, in 81% (17/21) of the patients. The reduction in the pulmonary vascular resistance was greater than that of the systemic resistance. In all patients, cardiac output increased. There was a similar number of responders to nitroglycerin (16/20). The reductions in mean pulmonary artery pressure and pulmonary arteriolar resistance ranging between 20 and 25% at rest and during exercise were comparable to those affected by nifedipine. In addition to the right ventricular afterload reduction, there was a decrease in cardiac output of 17%. During longterm treatment with nifedipine (average 18 months), the reduction in mean pulmonary artery pressure and pulmonary arteriolar resistance was not of the same magnitude as seen on acute testing. This may be due primarily to progression of the underlying disease since pulmonary function studies demonstrated an increase in the obstructive component. With the intention of circumventing or postponing the onset of right ventricular failure, the individual patient should undergo hemodynamic studies to delineate the optimal medication. PMID- 3093347 TI - [Present status and problems of mass screening--from the viewpoint of public health]. PMID- 3093346 TI - Persistent hemodynamic and clinical improvement after captopril in patients with pulmonary hypertension. AB - Ten patients with primary or secondary pulmonary hypertension who had normal left ventricular function (group I) and nine patients with pulmonary hypertension in response to impaired left ventricular function (group II) were given captopril. At peak effect (1.5 hours after administration) pulmonary vascular resistance fell from 935 to 717 dyn X s X cm-5 in group I and from 554 to 355 dyn X s X cm-5 in group II in association with a decrease in pulmonary arterial pressure by 8 and 12 mmHg, respectively (p less than 0.01). Systemic vascular resistance declined by 26 and 29 per cent, and cardiac index increased by 17 and 20 per cent, respectively (p less than 0.01). On re-catheterization four to 15 months later, seven chronically treated patients (five of group I; two of group II) showed additional reductions in pulmonary vascular resistance (25 per cent) and pulmonary arterial pressure (20 per cent), whereas systemic hemodynamics had almost reached pre-treatment values. All patients reported symptomatic improvement. The hemodynamic changes did not correlate with concomitant alterations in circulating renin or angiotensin II levels. These data suggest that captopril can produce sustained hemodynamic and clinical benefits in patients with pulmonary hypertension of various causes and may be useful for the chronic treatment of this disorder. PMID- 3093348 TI - [Promoting effect of oocytes and FSH on the growth of follicles]. AB - Immature follicles grow autonomously even without pituitary gonadotropins. In order to explore this reason, promoting effects of oocyte and some endocrinological substances on the proliferation of granulosa-cells (G-cells) have been investigated using the labelling index (LI) with 3H-Thymidine (3H-Tdr) and mitotic index (MI) in mature mice and immature hypophysectomized (hypox) rats. The following results were obtained: In preantral follicles with the oocyte diameter below 69 mu, the LI was low (9.5 +/- 1.7%) (m +/- SE) and the follicular diameter was small (69.0 +/- 7.7 mu). As the oocyte developed with its diameter 80-89 mu, the LI increased (20.3 +/- 3.8%) and the follicular diameter also increased (192.3 +/- 19.4 mu). In preantral follicles with the oocyte diameter over 80 mu the G-cells near the oocyte had a much higher LI than the distant G cells. After the antrum formation, the LI and MI of cumulus layers adjacent to the oocyte were three times higher than those of mural layers. Among the mural cell layers in the antral follicle, the layer adjacent to the antrum showed remarkably high LI in comparison with the distant layers. In FSH primed group the LI of G-cells was two fold higher than that in hypox control group (p less than 0.001). In the preantral follicle of hypox control group the G-cells near the oocyte had a much higher LI than the distant G-cells. Moreover in FSH primed group the LI indicated high value not only in the cell layers adjacent to the oocyte but also in the cell layers adjacent to the theca interna. In LH, E2 and P4 primed groups the LI of G-cells had no change significantly in comparison with that in hypox control group. In FSH + LH primed group the LI of G-cells decreased significantly in comparison with that in FSH primed group (p less than 0.05). In FSH + E2 group the LI had no change significantly in comparison with that in FSH primed group. These results suggest that the granulosa-cell growth factor (GGF) in oocyte, which seems to play a role in the formation of cumulus, is secreted with the growth of the oocyte. In antral follicles the GGF is transported through the follicular fluid.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3093349 TI - Effect of glibenclamide on thyroid hormone metabolism in rats. AB - This study was undertaken to elucidate the effect of glibenclamide, one of sulfonylurea drugs, on thyroid hormone metabolism in vivo and on the conversion of thyroxine (T4) to 3,5,3'-triiodothyronine (T3) in the isolated perfused rat liver and kidney. Glibenclamide (0.2 mg/kg body weight) was intraperitoneally administered to normal and streptozotocin-induced (50 mg/kg) diabetic rats for 14 days. The liver and kidney of normal rats were perfused for 30 minutes with a synthetic medium containing 20 micrograms/dl T4 and glibenclamide (200 or 400 ng/ml), and production of T3 in the tissues was measured by radioimmunoassay. Serum T4 and T3 levels in control and streptozotocin-induced diabetic rats were not changed by daily intraperitoneal glibenclamide administration. The production of T3 (111 +/- 40 and 95 +/- 16 ng/g/30 min, mean +/- SD) and the conversion rate of T4 to T3 (11.1 +/- 2.9 and 10.2 +/- 2.3%) in the liver perfused with glibenclamide (200 and 400 ng/ml) were not significantly different from those in controls (109 +/- 41 ng/g/30 min and 12.8 +/- 5.4%). And those (120 +/- 33 and 99 +/- 19 ng/g/30 min, and 3.5 +/- 0.6 and 2.5 +/- 0.4%) in the kidney perfused with glibenclamide (200 and 400 ng/ml) were similar to those in controls (98 +/- 33 ng/g/30 min and 3.0 +/- 1.5%). PMID- 3093350 TI - The behavior of hepatic phosphorylase b kinase, phosphorylase a and b after administration of glucagon to patients with glycogen storage disease type VIa. AB - In the patients with glycogen storage disease (GSD) type VIa and different serum glucose response to glucagon, the activities of hepatic phosphorylase b kinase, phosphorylase a and b were estimated before and after the intravenous administration of glucagon. 3 min after the administration of glucagon an increase in the activities of phosphorylase b kinase and phosphorylase a was found in liver tissue of all patients except one. These enzymatic activities, however, did not exceed the values of these enzymes in the control liver biopsies without glucagon loading. After the intravenous administration of glucagon an unsuspected increase of phosphorylase b activity was observed in the control liver tissues and in patients with GSD type VIa, except one. In vitro investigations revealed that an increase of hepatic phosphorylase b activity occurs during its conversion to phosphorylase a. We suppose that this phosphorylase b represents a partially phosphorylated form of this enzyme (an intermediate form) that is due to the action of the active phosphorylase b kinase. The correlations between the activities of phosphorylase b kinase, phosphorylase a and an intermediate form of phosphorylase b and hepatic glycogen degradation after administration of glucagon has been discussed. PMID- 3093352 TI - Plasma growth hormone releasing factor levels in children: physiological and pharmacologically induced variations. AB - Plasma growth hormone releasing factor (GHRH) was measured by RIA in the plasma of 41 children with constitutionally short stature. Basal plasma GHRH was 51 +/- 10 pg/ml. L-Dopa induced a 2-fold increase in circulating GHRH 30-45 min before the elevation of GH. A positive correlation (p less than 0.005) was found between the peak of GH and GHRH during the dopaminergic stimulus. On the opposite, the secretion of GH induced by amino acids or clonidine is not preceded by an elevation of plasma GHRH. When a release of GH appeared after the insertion of the venous catheter alone, probably due to the stress, it was preceded by a rise of plasma GHRH. In four sleeping adolescents during the night no relationship was found between the peaks of plasma GHRH and the peaks of GH secretion. These results suggest that the various stimulations of GH secretion used for investigations of a short stature do not act in the same way at the hypothalamo pituitary level. PMID- 3093351 TI - Effects of continuous LHRH infusion on plasma levels of LH and FSH in males, before and after oestrogen or anti-oestrogen treatment. AB - In order to study the role of oestrogens on gonadotrophin release in the human male, LHRH was administered as an infusion at a constant rate of 0.5 micrograms/minute for 4 hours to 7 normogonadotrophic oligozoospermic men, 6 eugonadal male-to-female transsexuals and 9 eugonadal male volunteers. In agreement with in vitro data a biphasic release pattern of both LH and FSH was observed in eugonadal transsexuals as well as in normogonadotrophic oligozoospermic men. In the latter the release of LH was greater than in eugonadal transsexual males and volunteers, which points to a different functioning of the hypothalamic-pituitary unit in normogonadotrophic oligozoospermic men. On the other hand the FSH response to LHRH stimulation was normal in these men. Three months' treatment with the oestrogen-receptor antagonist tamoxifen (TAM) (10 mg twice daily) in the normogonadotrophic oligozoospermic men stimulated basal LH, FSH and testosterone (T) levels. The fact that gonadotrophin levels rose in spite of increased T levels, suggests a role of endogenous oestrogens in the negative feedback regulation of gonadotrophin release in these men. Upon TAM treatment the first phase, the plateau and the second phase of LH release were augmented, whereas only the plateau and the second phase of FSH release were increased. Six weeks' administration of the oestrogen ethinyloestradiol (EE) (10 micrograms three times a day) in the eugonadal transsexual males suppressed basal T and oestradiol (E2) levels without affecting basal gonadotrophin levels significantly. In EE-treated males the first phase of LH release tended to be lower, whereas the plateau of LH had decreased significantly. The second phase of LH was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093353 TI - Therapeutic agents produced by genetic engineering: Quo vadis? The example of growth hormone and its releasing factor. Satellite symposium. Toulouse-Labege, May 29-30, 1985. PMID- 3093354 TI - Recent developments in the study of growth factors: GRF and somatomedins. Symposium. Paris, May 29-30, 1985. PMID- 3093356 TI - Investigation of human growth hormone releasing factor in adults. AB - A dose-effect relationship between human growth hormone (GH) releasing factor (hGRF) and GH response was demonstrated for doses ranging from 5 micrograms per subject (minimal active dose) to 40-80 micrograms per subject (minimal dose for maximal effect). Bioactivity of GH released under hGRF was proven in the Nb2 lymphoma cell multiplication assay. Unwanted effects were observed for doses equal to or larger than 150 micrograms. Pharmacokinetic parameters were calculated from the immunoreactive GRF plasma concentrations obtained after intravenous injections of various doses. The half-lives were 6.8 +/- 0.4 min and 43.2 +/- 3 min for distribution and elimination phases, respectively. Subcutaneous administration of hGRF was shown to be effective for promoting GH release, with doses higher than those required by intravenous administration. Intermittent intravenous injection of hGRF, at 3-hour intervals, resulted in a decrease in the magnitude of GH response in normal subjects. PMID- 3093355 TI - Clinical studies with GHRH in man. AB - GHRH was isolated from two GHRH-secreting pancreatic tumors which resulted in clinical acromegaly. Over 98% of acromegalic patients have a pituitary adenoma; however, acromegaly may occasionally result from ectopic or eutopic GHRH secretion. Administration of GHRH to normal adults stimulates growth hormone (GH) secretion; it may also stimulate GH release in some adults with GH deficiency in childhood and in a majority of GH-deficient children. Continuous infusion of GHRH to normal men stimulates GH secretion which augments naturally occurring GH pulses. GHRH is effective when administered subcutaneously and intranasally, but requires 30- and 300-fold higher doses, respectively. Intermittent subcutaneous GHRH therapy promotes acceleration of linear growth in GH-deficient children and appears promising as a treatment for these children. PMID- 3093357 TI - Effect of 16,16-dimethyl prostaglandin E2 on oxygen uptake and microcirculation in the perfused rat liver. AB - Previous work demonstrated that collagen deposition in the liver of rats fed a nutritionally deficient diet for 3 to 4 months was diminished markedly by 16,16 dimethyl prostaglandin E2 treatment. In this study, rats were fed a high-fat diet or a high-fat diet deficient in lipotropes for 2 to 4 weeks prior to liver perfusion. Rates of O2 uptake by the liver were not changed by dietary manipulation. Infusion of 16,16-dimethyl prostaglandin E2 (10 microM), however, decreased O2 uptake by the whole organ by 20 to 40% in both groups. O2 tension was measured at the liver surface with a miniature O2 electrode placed alternatively on periportal and pericentral regions of the liver lobule. Mean O2 tensions in both periportal and pericentral regions were reduced 2- to 3-fold during the infusion of 16,16-dimethyl prostaglandin E2 suggesting an action on the microcirculation. This hypothesis was supported by the observation that fluorescein isothiocyanate-dextran fluorescence detected from the liver surface as well as hepatic vascular volume determined by dye dilution techniques were decreased 30 to 50% by 16,16-dimethyl prostaglandin E2. In addition, 16,16 dimethyl prostaglandin E2 increased portal pressure by about 10 mm Hg in a reversible manner. Thus, it is concluded that pharmacological levels of 16,16 dimethyl prostaglandin E2 affects the microcirculation dramatically in the isolated perfused liver. PMID- 3093358 TI - Effects of anticonvulsant agents on halothane-induced liver injury in human subjects and experimental animals. AB - In order to evaluate the clinical implication of experimental studies on halothane-induced liver damage in phenobarbital-treated rats, we studied the clinical records of 315 consecutive patients who underwent brain surgery with halothane anesthesia. After exclusion of subjects with a history of alcoholism or antecedent chronic liver disease, clinical data of 279 patients with normal preoperative transaminase activities were analyzed. The incidence of halothane induced liver injury was significantly higher in the subjects given phenobarbital than in those with no phenobarbital medication (7/100 vs. 1/179, p less than 0.01). To determine if other anticonvulsant compounds can influence halothane induced liver injury, rats were pretreated with diphenylhydantoin or valproic acid prior to exposure to halothane under hypoxic conditions for comparison with phenobarbital. The degree of halothane hepatotoxicity assessed from ALT activities and morphological alterations was of the decreasing order of phenobarbital greater than controls = diphenylhydantoin greater than valproic acid, and a similar order was observed in the extent of reductive metabolism of halothane. These results indicate that patients pretreated with phenobarbital may be at a greater risk of halothane-induced liver damage, and that treatment with valproic acid and diphenylhydantoin lead to the production of toxic intermediates of halothane to a lesser extent than treatment with phenobarbital does. PMID- 3093359 TI - Relationship between guanase activity in donor blood and the incidence of posttransfusional non-A, non-B hepatitis, and a possible method for preventing posttransfusional hepatitis. AB - A total of 107 recipients, who did not show any evidence of hepatic disorders in pretransfusional liver function tests and gave a negative reaction for HBsAg, were observed from 3 weeks to 3 months after blood transfusion of 711 units of blood. The blood was judged suitable for use in transfusion because it had a normal level of ALT activity and gave a negative reaction for HBsAg. The guanase activities of the blood used for transfusion were examined. Cases in which an increase of ALT to at least twice the upper limit of normal persisted for at least 3 weeks and the ALT value increased to more than five times the normal upper limit at least once during this period, which also gave a negative reaction for HBsAg, were judged to have posttransfusional non-A, non-B hepatitis. Of 107 recipients, 18 developed posttransfusional non-A, non-B hepatitis. It was detected in 2 of 71 recipients (3%) with blood guanase activities below 3.5 units per liter and in 16 of 36 recipients (44%) with blood guanase activities above 3.6 units per liter. Thus, the incidence of posttransfusional non-A, non-B hepatitis was significantly higher in recipients with blood guanase activities above 3.6 units per liter. The incidence of posttransfusional non-A, non-B hepatitis increased linearly with increase in the level of guanase activity in donor blood. Thus, a high guanase activity in donor blood is considered to be an important predicting factor for posttransfusional non-A, non-B hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093360 TI - Human plasminogen activators. Genes and proteins structure. PMID- 3093361 TI - Molecular genetics of human B cell neoplasia. PMID- 3093362 TI - DRGs and mental health law: a glimpse of the future. PMID- 3093363 TI - The promise and pitfalls of purchase-of-service contracts. PMID- 3093364 TI - NJ hospitals react to the 'geriatric imperative'. PMID- 3093365 TI - Pediatric hospital group lobbies for children's DRGs. PMID- 3093367 TI - LTC insurance draws attention of state lawmakers. PMID- 3093366 TI - Does your grouper 'over-maximize' reimbursement? PMID- 3093368 TI - Despite obstacles, New Jersey excels in long-term care. PMID- 3093369 TI - Synaptophysin: a novel marker for neurons, certain neuroendocrine cells, and their neoplasms. PMID- 3093370 TI - Production and characterization of pepsin fragments of human IgA1 to determine domain-specificity of monoclonal anti-IgA antibodies. AB - Eight human IgA1 myeloma proteins were analysed by SDS-PAGE. These experiments showed that purified IgA1 proteins comprise both fully S-S bonded and partly S-S bonded molecules. Pepsin digestion of the IgA1 proteins yielded three four-chain and two two-chain fragments. The four-chain fragments are likely to be derived from intact IgA through cleavage of its alpha chains at different sites: between the CH2 and CH3 domains or in the hinge region. The occurrence of F(abc) (ab') fragments, with alpha chains of different lengths, showed that the alpha chains of IgA can be cleaved independently at the hinge region site. The two-chain pepsin fragments must originate from IgA molecules, which lack inter-assay-chain disulphide linkages. The fragments F(abc)2 and Fabc tended to form dimers, probably through non-covalent interactions of their CH2 domains. An immunoblotting method was used to identify Fd-, CH2- and CH3-specific anti-IgA antibodies. The CH2-specific antibodies could be subdivided into antibodies recognizing an isotype present on both four-chain and two-chain molecules or on two-chain molecules only. PMID- 3093372 TI - Specific adherence of thymocytes to a thymic medullary epithelial cell line. AB - TMF, a glycoprotein found preferentially at the contact points between thymocytes and thymic medullary epithelial cells, was investigated for its participation in adherence between these two cell types. It was found that thymocytes adhere specifically to a TMF+ cell line, that anti-TMF antibody can inhibit the adherence and that extraneous TMF can effectively compete with the adherence reaction. It is concluded that TMF is indeed involved in the temporary contact which occurs between thymocytes and medullary epithelial cells. PMID- 3093371 TI - Synergistic induction by calcium ionophore and phorbol ester of interleukin-2 (IL 2) receptor expression, IL-2 production, and proliferation in autoimmune MRL/MP lpr mice. AB - MRL/MP-lpr/lpr (MRL/l) mice spontaneously develop an age-related autoimmune disease concomitant with interleukin-2 (IL-2) defects. Induction of IL-2 receptor (IL-2R), IL-2 production and subsequent de novo DNA synthesis in MRL/l mice by the tumour-promoting phorbol ester 12-o-tetradecanoyl phorbol 13-acetate (TPA) and calcium ionophore (A23187) were examined. These two compounds given together induced significant IL-2R expression, IL-2 production, and de novo DNA synthesis of spleen cells from this murine strain, as did concanavalin A (Con A) plus TPA. TPA and A23187 may bypass the early steps of activation by mitogens in murine lymphocytes. However, even though these IL-2 defects could be overcome to some extent, the response of MRL/l mice to these stimuli was considerably lower than the enhanced IL-2R expression and IL-2 production of MRL/MP-+/+(MRL/n) control mice. These results suggested that the failure to respond to mitogens in these mice may be due, at least in part, to failure of receptor signal transduction, and to defects of molecular and biochemical reactions following signal transduction. PMID- 3093373 TI - Evolution of a V kappa gene family. AB - To examine the evolution of multigene families we have selected as an example an immunoglobulin light chain variable region subgroup (V kappa 24) which has been extensively characterized in inbred mice (mus musculus domesticus). Homologous genes have been isolated and sequenced from Mus pahari, a genetically and geographically isolated species believed to be the oldest living representative of the genus. Southern blot analysis using probes corresponding to individual genes in this subgroup reveals changes in the overall size of the family occurring at the level of individual genes but not at the level of the entire family. Nucleotide sequence analysis indicates an absence of regulatory sequences such as the CAT and TATA boxes 5' to the coding region, but a decanucleotide sequence involved in light chain expression is highly conserved. Within coding regions highly complex patterns of variation are seen which appear to reflect quite different selective pressures on various subregions of the coding sequence. Complementarity determining regions (CDR) are conserved to different extents, with the first CDR region in all family members being among the most conserved segments of the molecule. Conservation is similarly variable among framework segments, indicating complex and variable evolutionary pressures not only at the level of individual genes or their products but also at subregions within homologous molecules. PMID- 3093374 TI - New concepts in autoimmunity. PMID- 3093375 TI - The oral immune system: dynamics of salivary immunoglobulin production in the inbred mouse. AB - In the oral cavity, salivary immunoglobulins (Igs) are the principal mediators of specific immunity. Using carbachol to stimulate saliva flow, we investigated, in a kinetic study, individual variations in salivary Ig concentrations in 23 adult BALB/c mice using an enzyme-linked immunosorbant assay (ELISA). It appeared that salivary Ig concentrations are highly variable in individual mice (IgA: 3-81 micrograms/mL; IgG: 0-2.9 micrograms/mL; IgM: 0.002-0.14 microgram/mL). In individual mice stimulated at different times over a 3 week period there are considerable variations both in salivary Ig concentrations and in their respective ratio. Broad variations were also found in the levels of specific IgA and IgG antibodies to three indigenous oral murine bacteria. Present data thus indicate that among genetically identical mice of the same age and sex, sharing identical diet, there is considerable heterogeneity in salivary Igs. As this heterogeneity was mimicked at the cellular level in major and minor salivary gland-associated B-cells, it appears that antibody dynamics in the oral cavity could reflect the adaptive capacity of the oral immune system to local antigenic challenge. PMID- 3093376 TI - Effect of membrane cholesterol depletion on the immunoreactivity of the D antigen and IgG anti-D. AB - The immunoreactivity of the main Rh antigen (D) and its corresponding antibody, as determined by a ti-IgG to IgG combining ratio, antibody dissociation and antigen accessibility to antibody, was examined in cholesterol depleted human red cells and ghost membranes. The anti-IgG reactivity of IgG anti-D bound to cholesterol depleted red cells and ghosts was demonstrably enhanced in vitro and in electron microscopy studies, particularly in ghosts. Dissociation of cell bound anti-D during buffer incubation was greater after cholesterol depletion, especially in ghosts. There was also reduced binding of anti-D to cholesterol depleted cells as previously reported. All these effects appeared to be independent of endogenous or exogenous proteolysis in either cholesterol-depleted membranes or controls as judged from membrane electrophoretic analyses. A2C, an agent which increases membrane fluidity, had no effect on anti-D binding or the antiglobulin reactivity of cell bound IgG. A reduction in anti-D binding also was observed in red cells depleted of cholesterol following immobilization of membrane proteins by glutaraldehyde crosslinking. The findings show that cholesterol depletion not only affects the antigen but also Rh antibody reactivity. They also suggest that factors other than vertical antigen movement in a fluid bilayer may influence the behavior of the D antigen in cholesterol modified erythrocytes. PMID- 3093377 TI - Effect of RO 15-1788 on diazepam, GABA & pentobarbitone induced EEG changes in rabbits. PMID- 3093378 TI - Prevalence of Crimean haemorrhagic fever--Congo virus in Jammu & Kashmir state. PMID- 3093379 TI - Etiology of acute gastroenteritis in malnutrition. PMID- 3093380 TI - A concentrated mixture of amino acids and dipeptides for total parenteral nutrition. AB - Using a subhuman primate (baboon) we have investigated the utility of a 20% mixture of amino acids and dipeptides as the nitrogen source for total parental nutrition. The mixture, besides containing all 8 essential amino acids and a number of non-essential amino acids (glutamate, aspartate, arginine, histidine, serine, ornithine and alanine), contained 6 dipeptides (Gly-Ile, Gly-Leu, Gly Val, Gly-Tyr, Gly-Gln, and Ala-Gln) and acetyl-cysteine. A week of total parenteral nutrition was preceded by one week of oral feeding. The caloric intake and composition during the two periods was identical except for the nitrogen source, which was intact protein during the oral period, and the mixture of amino acids and dipeptides during the parenteral period. There was no significant difference between gain in body weight or nitrogen balance during the two periods. There were selective increases in plasma and muscle concentrations of amino acids during the parenteral period, which appeared to reflect the amino acid enrichment of the nitrogen source. The efficient utilization of dipeptides was evidenced by their small concentrations in plasma and urine. The urinary excretion of dipeptides was about 1% of the amount infused. This efficiency of dipeptide utilization persisted even when the infusion rate of the amino acid and dipeptide mixture was increased by 7-fold. There was no alteration in liver, kidney, and immune function during the parenteral period. The data indicate the efficacy and safety of the mixture of amino acids and dipeptides as the nitrogen source for parenteral nutrition. PMID- 3093381 TI - Characterization of a protein from normal human polymorphonuclear leukocytes with bactericidal activity against Pseudomonas aeruginosa. AB - Purification of a bactericidal protein (BP) from the cytoplasmic granules of normal human polymorphonuclear leukocytes (PMN) with activity against Pseudomonas aeruginosa is described. Bactericidal activity from acid extracts of a mixed granule population was purified 175-fold by a two-step chromatographic procedure. The first step, dye-ligand affinity chromatography with Matrex-Gel Orange A, was followed by cation-exchange chromatography with Bio-Rex 70 resin, and this combination routinely gave a yield near 80%. Only one peak of bactericidal activity against P. aeruginosa type I was found after each chromatographic step. Characterization of BP showed a single band with an apparent molecular weight of 55,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Purified BP was most active against the six strains of P. aeruginosa tested and against Escherichia coli B (a deep rough mutant). Purified BP killed 5 X 10(6) CFU of P. aeruginosa type I per ml at a concentration of 60 to 80 ng/ml. Proteus mirabilis and Staphylococcus aureus were both resistant to the bactericidal activity of BP. BP was shown to be glycosylated by periodic acid staining after gel electrophoresis and to have an isoelectric point near 7.5 by chromatofocusing. The amino acid composition of BP is presented. PMID- 3093383 TI - Immunopotentiating activities of cell walls, peptidoglycans, and teichoic acids from two strains of Listeria monocytogenes. AB - Crude cell wall (CCW), enzyme purified wall (PF), peptidoglycans (PEP), and teichoic acid fractions from two strains of Listeria monocytogenes (EGD and a human isolate) were analyzed by electron microscopy, chemical analyses, and various immunological assays. Electron microscopy and chemical analyses revealed that both strains were quite similar. The CCW, PF, and PEP fractions were mitogenic for mouse lymphocytes, could activate macrophages in vivo but not in vitro, and stimulated nonspecific immunity in vivo to Candida albicans. The PF and PEP fractions but not the CCW induced migration inhibition factor production. The CCW and PEP fractions were tested and found to elevate natural killer activity in vivo. Teichoic acid fractions had no activity in the above assays. Since most of the immunological activities were retained in the PEP fraction, we examined this fraction to determine the kinetics of the mitogenic response and the nature of the responding cell population. The peak mitogenic response occurred on day 2 over a 6-day period. This response was not enriched in T-cell enriched populations but followed the pattern of LPS in B-cell-enriched populations. PMID- 3093382 TI - Degradation of soluble laminin and depletion of tissue-associated basement membrane laminin by Pseudomonas aeruginosa elastase and alkaline protease. AB - Purified Pseudomonas aeruginosa elastase and alkaline protease rapidly cleaved soluble laminin, with each enzyme yielding different cleavage products. These cleavage fragments were separated from the intact laminin A and B polypeptide chains by sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis and detected by their characteristic Coomassie blue staining patterns. Pseudomonas elastase produced rapid and extensive degradation of both A and B chains, including the disulfide-rich regions. Apparently complete degradation to limit digests was obtained after 30 min with a substrate/enzyme ratio of 30:0.5. Under similar conditions, alkaline protease rapidly degraded the A chain while slowly degrading the B chain. In addition, immunoreactive laminin was released from authentic basement membranes after incubation with either enzyme as detected by an enzyme-linked immunoabsorption assay and by immunofluorescence. The results from these studies suggest a direct role for elastase and alkaline protease in both tissue invasion and hemorrhagic tissue necrosis in P. aeruginosa infections. PMID- 3093384 TI - Antigonococcal activity of human neutrophil cathepsin G. AB - We have shown that lysosomal cathepsin G, prepared from acid extracts of granules derived from human polymorphonuclear granulocytes, exhibits potent in vitro antimicrobial activity against Neisseria gonorrhoeae. An isolated isozyme of cathepsin G was found to exhibit antigonococcal activity by a nonenzymatic mechanism in a time-dependent manner. Moreover, we observed that the antigonococcal activity of cathepsin G was relatively independent of pH and evident over a pH range resembling that invoked for maturing phagolysosomes. Using a number of isogenic strains, we determined that certain mutations known to alter cell envelope structure rendered gonococci more susceptible to cathepsin G. This suggests that the susceptibility of gonococci to cathepsin G, and possibly other antimicrobial proteins derived from PMN granules, is genetically determined and possibly related to the structure of the gonococcal cell envelope. PMID- 3093385 TI - Polyclonal and monoclonal antibody therapy for experimental Pseudomonas aeruginosa pneumonia. AB - A human immunoglobulin G preparation, enriched in antibodies to lipopolysaccharide (LPS) Pseudomonas aeruginosa antigens (PA-IGIV) and murine monoclonal antibodies (MAb) to P. aeruginosa Fisher immunotype-1 (IT-1) LPS antigen and outer membrane protein F (porin), were evaluated for therapeutic efficacy in a guinea pig model of P. aeruginosa pneumonia. The concentration of antibodies to IT-1 LPS was 7.6 micrograms/ml in PA-IGIV and 478 micrograms/ml in the IT-1 MAb preparation. No antibody to IT-1 was detected in MAb to porin. For study, animals were infected by intratracheal instillation of IT-1 P. aeruginosa and then treated 2 h later with intravenous infusions of PA-IGIV, IT-1 MAb, or porin MAb. Control groups received intravenous albumin, and routinely died from pneumonia. Both PA-IGIV (500 mg/kg) and IT-1 MAb (greater than or equal to 2.5 mg/kg) treatment resulted in increased survival (P less than 0.01 to 0.001), and also improved intrapulmonary killing of bacteria. Porin MAb failed to protect from fatal pneumonia. IT-1 MAb treatment produced more survivals than did PA-IGIV treatment but only at dosages of MAb resulting in serum antibody concentrations greater than those achieved with PA-IGIV. PA-IGIV and IT-1 MAb demonstrated in vitro and in vivo (posttreatment guinea pig serum) opsonophagocytic activity for the IT-1 challenge strain. However, the polyclonal preparation required complement, whereas the MAb did not. We conclude that passive immunization with polyclonal hyperimmune P. aeruginosa globulin or with MAb to LPS antigens may be useful in the treatment of acute P. aeruginosa pneumonia. The relative efficacies of such preparations may be limited, however, by their type-specific LPS antibody concentrations. PMID- 3093386 TI - Transfer of the plasmid for exfoliative toxin B synthesis in mixed cultures on nitrocellulose membranes. AB - Plasmid pRW002 carries genetic determinants for exfoliative toxin B and bacteriocin R1 synthesis. When a donor strain carrying plasmid pRW002 was mixed with a plasmidless recipient strain on a nitrocellulose membrane in accordance with the procedure used for staphylococcal conjugation, pRW002 was passed to the recipient by mixed-culture transduction. Transfer was inhibited by citrate and serotype B phage antisera but not by DNase I. Cell-to-cell contact was not required, and transfer frequencies increased more than 10-fold in the presence of small concentrations of mitomycin C. These results are consistent with pRW002 transfer in mixed cultures by transduction and not by conjugation or transformation. Immunodiffusion and DNA analyses after agarose gel electrophoresis demonstrated that transductants were exfoliative toxin B producers and housed pRW002. Since mixed-culture transfer has been reported to occur on skin, our results suggest that mixed-culture transduction might be a mechanism for the transfer of genetic determinants for pathogenicity in vivo. PMID- 3093387 TI - [In vitro activity of new quinolones against nonfermenters and references to sensitivity tests]. AB - Studies of cross resistance between norfloxacin, ofloxacin, enoxacin and ciprofloxacin using 599 strains of non-fermentative gram-negative rods (297 Pseudomonas spp. and 302 Acinetobacter spp.) resulted in nearly identical minimal inhibitory concentrations of norfloxacin and enoxacin Comparing MIC values, in most ofloxacin was one to four dilution steps superior to enoxacin, and ciprofloxacin was one to four dilution steps superior to ofloxacin. There was not much difference in MICs when species were studied in more detail. In some instances susceptibility testing with more than one new quinolone may be necessary, and evaluation criteria are given. PMID- 3093388 TI - [Short communication about the influence of quinolone derivatives on the immune system]. PMID- 3093389 TI - Purification and physicochemical characterization of Schistosoma mansoni egg allergen recognized by mouse sera obtained at an acute stage of infection. AB - A major allergenic component recognized by mouse sera obtained at an acute stage of infection was purified from soluble egg antigen preparation (SEA) of Schistosoma mansoni by anion-exchange chromatography on DE52 and gel chromatography on Sephadex G-150. The purified allergen showed homogeneity by immunoelectrophoresis and by polyacrylamide gel electrophoresis. Its apparent molecular weight was 210,000 by gel chromatography on Sephadex G-200. This purified allergen could bind to Con A-Sepharose 4B, indicating its glycoprotein nature. After amino acid analysis, aspartic acid, glutamic acid, serine and theonine were found as the major amino acids. The allergenic activity was destroyed by heating at 100 degrees C for 60 min and by pronase or periodate treatment. By double diffusion in agar gel, this purified allergen gave a strong single band against acute (8 w) stage serum, which fused to the major band formed by crude SEA. On the other hand, it showed a very faint band against chronic (22 w) stage serum, which is apparently different from the main band formed between crude SEA and the chronic stage serum. When specific IgE or IgG antibody titers in the serum of human schistosomiasis mansoni cases were measured by ELISA using this purified allergen, the results showed good correlation with those obtained by using crude SEA. Thus, this purified allergen is not only a major allergen in the acute stage of murine schistosomiasis but also an allergen in human schistosomiasis mansoni. PMID- 3093390 TI - Synergism of recombinant human interferon gamma with liposome-encapsulated muramyl tripeptide in activation of the tumoricidal properties of human monocytes. AB - Freshly isolated human peripheral blood monocytes from healthy volunteers are not cytotoxic to allogeneic A375 melanoma cells, but they were rendered tumoricidal by incubation in vitro with either liposomes containing 5 micrograms/mumol phospholipid of muramyl tripeptide phosphatidylethanolamine (liposome-MTP-PE; optimal dose, 500 nmol/ml) or recombinant human interferon gamma (rIFN-gamma; optimal dose, 100 U/ml). A combination of sub-threshold concentrations of liposome-MTP-PE (50 nmol/ml) and rIFN-gamma (1 or 10 U/ml) also induced significant tumor-cell killing, indicating that the effects of rIFN-gamma and liposome-MTP-PE in monocyte activation are synergistic. In contrast to rIFN gamma, recombinant IFN-alpha and IFN-beta had additive effects with liposome-MTP PE in human monocyte activation. Since recombinant human IFN-gamma has a synergistic effect with liposome-MTP-PE in monocyte activation, unlike IFN-alpha or IFN-beta, and liposome-MTP-PE as well as rIFN-gamma is available at standardized concentrations, this combination could be of clinical value in the treatment of disseminated malignant disease. PMID- 3093391 TI - A case-control study of the efficacy of a non-randomized breast cancer screening program in Florence (Italy). AB - In a rural area near Florence a population-based screening program for breast cancer was started in 1970, offering a mammography test every 2.5 years to all women between 40 and 70 years of age. In order to evaluate the efficacy of this program a case-control study has been carried out comparing the screening history of all women who died from breast cancer in this area in the years 1977-1984, and who had been diagnosed after the start of the program, with that of a matched group of living controls. The case-control study showed that the overall O.R. of dying from breast cancer in the study period for "screened" versus "never screened" women was 0.53 (95% C.I. = 0.29-0.95). After evaluation of other variables as potential confounders the adjusted O.R. estimates were respectively 0.57 (95% C.I. = 0.35-0.92) and 0.32 (95% C.I. = 0.20-0.52) for women screened only once or at least twice. No significant protective effect was shown for women below the age of 50 years. PMID- 3093392 TI - Phenotypic profile of clones from early cultures of human metastatic melanomas and its modulation by recombinant interferon gamma. AB - Fifty-six tumor clones isolated by cloning in soft agar from early cultures (before the 10th in vitro passage) of two different human metastatic melanomas (Me9229 and Me28) were characterized by FACS analysis for surface expression of class-I and class-II HLA antigens and of melanoma-associated antigens (MAA) with a panel of 15 monoclonal antibodies (MAbs). A marked phenotypic heterogeneity involving MAA and/or HLA markers was observed among the clones derived from both tumors. The differences among the tumor clones and between them and the uncloned melanoma were qualitative and quantitative for each antigen considered. Clones derived from Me9229 expressed the same HLA profile as the parental culture (class I+, class II-) while strong heterogeneity was observed for MAA expression. Clones from Me28 presented a marked heterogeneity for class-I and class-II HLA antigens but were more homogeneous for MAA. The phenotype of the clones was repeatedly checked over the first month in culture and found to remain generally unchanged and not linked to the cell cycle. However, major changes in antigenic expression of the clones could be observed upon treatment with recombinant interferon-gamma (rIFN-gamma): class-I and -II HLA antigens could be induced or augmented while a moderate inhibition was seen on MAA expression. Furthermore, an apparent hierarchy in expression and/or induction of class-II antigens by rIFN-gamma was observed among the tumor clones. DR antigens were more frequently expressed (Me28 clones) and upon treatment with rIFN-gamma reached higher levels than DP and DQ products. Taken together these results indicate that antigenic heterogeneity for MAA and HLA antigens can be detected in cells isolated from early cultures of human metastatic melanomas and suggest that the original uncloned tumor might be considered as a complex mixed population made up of a number of neoplastic cells each expressing a distinct phenotype which can be modulated by lymphokines such as IFN-gamma. PMID- 3093393 TI - Two new cell lines from B-prolymphocytic leukaemia: characterization by morphology, immunological markers, karyotype and Ig gene rearrangement. AB - Leukaemic cells from 2 patients with B-prolymphocytic leukaemia were immortalized in vitro by means of Epstein-Barr virus and phorbol-ester TPA. The resulting cell lines, named JVM-2 and JVM-3, have been growing continuously in liquid culture for more than one year. JVM-2 is characterized cytogenetically by t(11;14)(q13; q32), and JVM-3 by trisomy 12. The immunoglobulin (Ig) heavy- and light-chain genes showed the same pattern of rearrangement in both lines as in the original prolymphocytes from each case. The cells from these lines showed a spectrum of morphological and immunological features corresponding to different stages of B cell maturation. The expression of Ig, IgM-lambda in JVM-2 and IgMD-K in JVM-3, changed from a predominantly membrane pattern in the original cells to a cytoplasmic one in the cell lines. By comparison with their original progenitors, the cells from both lines showed reduced reactivity with the monoclonal antibody (MAb) FMC7, and increased expression of the antigens recognized by the MAbs OKT10, alpha-Tac, FMC53 and Ki-I. The availability of cell lines from this rare type of lymphoid leukaemia offers a potential tool for the study of molecular events associated with the expression of Ig and other antigens by neoplastic cells. PMID- 3093394 TI - Specificity of a monoclonal antibody to Drosophila melanogaster neoplastic hematopoietic cell surfaces as detected by immunofluorescence. AB - We have generated, and characterized the immunological specificity of, a monoclonal antibody (MAb) termed 2B3G8 that recognizes cell-surface determinant(s) of D. melanogaster neoplastic hematopoietic tissue. This antibody was generated against antigens of a tumor line derived from neoplastic lymph glands, the hematopoietic organs, of a growth control mutant, Tumorous-lethal (Tum1). 2B3G8 does not recognize any of a panel of normal Drosophila cells or transformed cell lines from mouse or human sources as assayed by indirect immunofluorescence. Enzymatic digests did not remove this antigen from neoplastic blood cells or uncover the antigen in normal blood cells. Thus, we have generated a MAb that serves as a marker for the neoplastic hematopoietic condition in Drosophila which is a model for vertebrate neoplasia. This antibody is potentially useful for the study of oncodevelopmental antigens in developing hematopoietic systems and for detecting the onset of the neoplastic condition. PMID- 3093395 TI - Endometrial morphology during long-term use of levonorgestrel-releasing intrauterine devices. AB - Levonorgestrel-releasing intrauterine devices (IUD) were inserted in 92 women. Endometrial biopsies were taken between 3 months and 7 years after these insertions. Intrauterine release of levonorgestrel resulted in endometrial glandular atrophy and decidualized stroma. Inflammation and necrosis were also seen as local signs of IUD use. The biopsies were similar regardless of the duration of IUD use. Endometrial morphology returned to normal in biopsy specimens taken 1-3 months after IUD removal. PMID- 3093396 TI - Of soap and Semmelweis. PMID- 3093397 TI - A hospital cafeteria-related food-borne outbreak due to Bacillus cereus: unique features. AB - Although Bacillus cereus is a well-known cause of food-borne illness, hospital related outbreaks of food-borne disease due to B. cereus have rarely been documented. We report a hospital employee cafeteria outbreak due to foods contaminated with B. cereus in which an outside caterer was employed to prepare the suspect meals. Data were collected from 249 of 291 employees who had eaten either of the two meals. With a mean incubation period of 12.5 hours, 64% (160 of 249) of employees manifested illness. Symptoms, which averaged 24.3 hours in duration, included diarrhea (96.3%), abdominal cramps (90%), nausea (50.6%), weakness (24.7%), and vomiting (13.8%). Eighty-seven employees sought medical attention, 84 of whom were seen in an emergency room. Although a significant difference was not demonstrated in food-specific attack rates, B. cereus was cultured from both rice and chicken items that were served at both meals. Sixty three employees submitted stools for culture that grew no enteric pathogens, but none were examined for B. cereus. This food-borne outbreak demonstrates: the need for hospital kitchen supervisors to ensure proper handling of food when outside caterers are employed; that significant differences in food-specific attack rates may not be demonstrated in outbreaks, which may be related to several factors; and the importance of notifying microbiology laboratory personnel when B. cereus is a suspect enteric pathogen, since many laboratories do not routinely attempt to identify this organism in stool specimens. PMID- 3093398 TI - Infection control software for microcomputers. PMID- 3093399 TI - [Superfluous thyroid diagnosis]. PMID- 3093400 TI - Arachidonic acid metabolism to eicosanoids in herpes virus-infected rabbit cornea. AB - The metabolism of the polyunsaturated fatty acid, arachidonic acid (20:4, n-6) in rabbit cornea with varying severities of herpes simplex viral infection was investigated. The results indicate an active synthesis of the lipoxygenase and cyclooxygenase reaction products of arachidonic acid in central cornea and corneal-scleral rim. Stimulation of 12-hydroxyeicosatetraenoic acid (12-HETE) production in herpes-infected cornea was correlated positively with the severity of infection. Other eicosanoids were increased maximally in moderately infected corneas. The stimulation of eicosanoid synthesis was more evident in central cornea as compared to corneal-scleral rim. Herpes infection also caused a decline in the incorporation of radiolabeled arachidonic acid into membrane glycerolipids. These data indicate that the production of eicosanoids from arachidonic acid is stimulated in herpes-infected cornea. The stimulation may reflect the presence of phagocytic cells in the infected cornea, an enhanced capacity of the cornea itself to produce eicosanoids, or a combination of these effects. Decreased acylation of membrane lipids may be the result of infection induced activation of fatty acid release mechanisms, which would lead to degradation of cell membranes. The presence of lipoxygenase reaction products in the herpes-infected cornea introduces a new factor for consideration in the design of therapeutic regimens for this disease. PMID- 3093401 TI - End-tidal carbon dioxide levels and the sudden infant death syndrome. PMID- 3093403 TI - Pulmonary ossification. PMID- 3093402 TI - Postnatal development of corticocortical connections. AB - In the course of normal development transitory corticocortical projections are formed within each hemisphere and between the two hemispheres. The organization of the transitory projections and the main events in their elimination have been investigated. Experiments on visual areas of the cat indicate that the elimination/stabilization of a fraction of the juvenile projections depends on activity. PMID- 3093405 TI - The intensive care unit population within the prospective payment scheme. PMID- 3093406 TI - An unusual complication of intravenous nitroglycerin. AB - Intravenous nitroglycerin is frequently used in the treatment of acute myocardial infarction for its vasodilating effect on lowering both preload and afterload and in the control of ischemic heart pain. The end point for doses of nitroglycerin infusion is either relief of persistent or recurrent angina or controlling congestive heart failure by lowering left ventricular end diastolic pressure and volume. Nitroglycerin accomplishes these end points primarily through its venodilating property. Intolerable headaches or symptomatic hypotension may prevent achieving the clinical end point. Nevertheless, high doses of intravenous nitroglycerin may need to be administered to achieve a desired hemodynamic and therapeutic effect. Changes in mental status, i.e., lethargy and confusion, should be a warning sign of possible ethanol intoxication. An alcohol blood level verifies the clinical impression and gradually withdrawing the intravenous nitroglycerin is all that is necessary to effect a total recovery from this reaction. PMID- 3093404 TI - Prolactin stimulation of ornithine decarboxylase and mitogenesis in Nb2 node lymphoma cells: the role of protein kinase C and calcium mobilization. AB - The tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with calcium ionophores has been shown to bypass the requisite antigen- or lectin induced signal for lymphocyte mitogenesis. This suggests that protein kinase C activation and calcium mobilization may be early events required for lymphocyte proliferation. Therefore, the relationship(s) of protein kinase C activation and calcium mobilization to ornithine decarboxylase induction and cellular proliferation were examined in a rat node lymphoma cell line (Nb2) which is dependent upon prolactin (PRL) for mitogenesis. TPA enhanced PRL-stimulated Nb2 node lymphoma cell ornithine decarboxylase induction and [3H]thymidine incorporation. Addition of a calcium ionophore (A23187) to cultures containing TPA plus PRL increased ornithine decarboxylase above PRL alone or PRL plus TPA but inhibited proliferation compared to the PRL plus TPA regimen. Exposure of cells to TPA or TPA plus A23187 increased [3H]thymidine incorporation in a similar manner to that demonstrated for low-dose PRL. However, optimal concentrations were only 20-25% as effective as mitogens as was optimal PRL. Protein kinase C and calmodulin antagonists inhibited PRL-stimulated ornithine decarboxylase induction and proliferation. Ca2+ chelation or cation channel antagonism inhibited both PRL-stimulated responses. The cyclic AMP analogue, 8Br cAMP, inhibited PRL-stimulated ornithine decarboxylase activity as well as cellular proliferation processes assessed by [3H]thymidine incorporation. Finally, tumor-promoting phorbol esters inhibited 125I-rPRL binding. These data strongly suggest that protein kinase C activation and calcium mobilization are requisite events for PRL-stimulated ornithine decarboxylase induction and cellular proliferation in Nb2 node lymphoma cells. An additional component that is linked to alterations in K+ channeling is also implicated. These data support a role for protein kinase C in PRL-coupled mitogenesis. However, other critical Ca2+ and/or ion-induced events are also required. PMID- 3093407 TI - The clinical usefulness of measuring apolipoproteins in diabetic patients: a preliminary report. PMID- 3093408 TI - Evaluation of the economic impact of pharmacist involvement in hyperalimentation therapy. PMID- 3093409 TI - The effects of different fixatives for immunofluorescent and immunoperoxidase localization of factor VIII-related antigen in canine carotid artery and vascular prostheses. AB - The evaluation of vascular grafts seeded with autologous endothelial cells requires a reliable method of endothelial cell identification. Previous attempts to identify positively tissue Factor VIII-related antigen, found in relatively large amounts in vascular endothelial cells, proved to be inconsistent when immunoperoxidase and immunofluorescent staining techniques were tried. Because the Factor VIII antigen is very labile, this study was performed to determine an optimal fixation technique for demonstrating this antigen in frozen sections of endothelial tissue. Unfixed, acetone-fixed, and formalin-fixed sections of canine carotid artery as well as vascular grafts fixed in 1-ethyl-3-(3-diaminopropyl) carbodiimide were examined by an indirect immunofluorescence technique. Also, the immunoperoxidase method of Factor VIII identification was applied to unfixed, acetone-fixed, and carbodiimide-fixed endothelial cell seeded vascular grafts. Acetone was the preferred fixative, resulting in excellent antigen preservation with minimal background staining. The immunoperoxidase technique of Factor VIII related antigen identification was found to be the method of choice because of its sensitivity. PMID- 3093410 TI - A quantitative histochemical study of NADPH-ferrihemoprotein reductase activity. AB - A quantitative histochemical assay for NADPH-ferrihemoprotein (P450) reductase had been developed. For optimal activity, it is necessary to use a relatively electropositive tetrazolium salt such as neotetrazolium chloride as the final acceptor. The apparent Km of the reaction is 0.83 mM. Its specificity has been proven in two ways: (i) activity is increased selectively in the pericentral zone of liver from rats treated with phenobarbitone, an inducer of the reductase, though not in liver of rats injected with 3-methylcholanthrene, which induces NAD(P)H dehydrogenase; (ii) it is competitively inhibited by NADP+ (Ki = 1.50 mM) though unaffected by dicumarol, an inhibitor of NAD(P)H dehydrogenase activity. An NADP+ concentration ten times greater than the substrate concentration inhibits the histochemical reaction and the reaction in a microsomal fraction assayed biochemically to the same degree (70% inhibition). The amount of inhibition is independent of temperature, of the zone of the acinus and of the treatment of the animal. Continuous microdensitometric monitoring of the reaction product as it is formed has shown that the specific reaction is linear with incubation up to 10 min, thus allowing end-point measurements to be used for cytophotometric analysis. PMID- 3093411 TI - Unusual binding sites for horseradish peroxidase on the surface of cultured and isolated mammalian cells. Suppression of binding by certain nucleotides and glycoproteins, and a role for calcium. AB - Binding sites for horseradish peroxidase (HRP), with unusual properties, were detected on the surface of cultured and isolated cells after the cells (on cover slips) had been quickly dried, fixed in cold methanol, and post-fixed in a paraformaldehyde solution. The reaction for surface-bound HRP was suppressed by micromolar concentrations of glycoproteins such as invertase, equine luteinizing hormone (eLH) or human chorionic gonadotropin (hCG). The reaction was also suppressed by 20 mM CDP, UDP, GTP, NAD, and ribose 5-phosphate. Two to six times higher concentrations of GMP, fructose 1-phosphate, galactose 6-phosphate, mannose 6-phosphate, fructose 6-phosphate, and glucose 6-phosphate were required to suppress the binding reaction. AMP, ATP, heparin, mannan, and eight non phosphorylated sugars showed relatively low competing potencies but fucoidin and alpha-lactalbumin were strong inhibitors. No addition of Ca2+ was required for the binding of HRP to the cell surface. However, calcium-depleted, inactive HRP did not compete with the binding of native (calcium-containing) HRP whereas H2O2 inactivated HRP suppressed the binding. GTP, NAD, ribose 5-phosphate, and EGTA accelerated the release of previously-bound HRP from the cell surface whereas glycoproteins (invertase, eLH, and hCG) did not do so. Addition of Ca2+ to GTP, NAD, ribose 5-phosphate or to EGTA prevented the accelerated release of HRP from the cell surface. It is suggested that calcium, present either in the surface membrane or in HRP itself, is involved in the binding of HRP to the cell surface and in the inhibition of binding by GTP, NAD, and ribose 5-phosphate. It is also suggested that alpha-lactalbumin, GTP, UDP, and CDP compete with the binding of HRP to a glycosyltransferase on the cell surface. PMID- 3093412 TI - Immunogenetic profile of multiple sclerosis in Mexicans. AB - This is the first study on genetic markers in Mexican Mestizos with multiple sclerosis (MS). Patients were born in Mexico, had no family history of MS are middle-class, and have a high-level education. HLA class I, class II determinants, C2, C4, BF, GLO-1, ABO, and Rb red cell systems were analyzed and compared with results of 295 controls. Measles antibodies, glucose, IgG, total proteins, and cell count were measured in cerebrospinal fluid; anti-neuron, T cell, and B-cell antibodies were determined in serum. MS in Mexican Mestizos was clinically similar to MS reported in high prevalence countries. DRw6, as previously found in Japanese patients, and its subtype, DRw13, were increased in patients in our study (pc = 0.0007, pc = 0.01, respectively), and the combination A3, B7, DR2, was also elevated (pc = 0.003). The polygenicity of the disease is emphasized by the excess of AB group carriers (pc = 0.01). IgG levels were high in patients with DR2 or DRw6 and 67% of the latter had anti-T cell antibodies. Severity of the disease was also related to the DR markers. It is suggested that at least two HLA-DR linked genes and the industrialized environment are important for the expression of MS in Mestizos. PMID- 3093413 TI - Microangiopathic hemolytic anemia, noncardiac pulmonary edema, and renal failure after treatment of metastatic adenocarcinoma of the colon with 5-fluorouracil and mitomycin-C: report of a case. PMID- 3093414 TI - The influence of hemoglobin level on the regression and long term local control of transitional cell carcinoma of the bladder following photon irradiation. AB - Patients with transitional cell carcinoma of the bladder treated by radical megavoltage X ray therapy are analyzed. There was a significant correlation between tumor T stage classification and the hemoglobin level at the start of radical radiotherapy. A hemoglobin level of 12g/dl or more was associated with a significant improvement in complete local tumor regression at 6 months and durable local tumor control for patients with T3 cancer or a cancer of grade 3 histology. Hemoglobin level did not influence survival for patients with T1 or grade 1 cancer. Those patients with T2-T4 cancer, grade 2-3 cancer, or a cancer of solid or mixed appearance had a significantly better survival probability if their hemoglobin level was more than 13g/dl. Hemoglobin level would appear to exert its influence on survival by an effect on local tumor control. It has no significant independent effect on the hazard of distant metastases. PMID- 3093415 TI - Effects of dose and scheduling on growth delay of the Lewis lung carcinoma produced by the perfluorochemical emulsion, Fluosol-DA. AB - The perfluorochemical emulsion, Fluosol-DA, combined with breathing a 95% oxygen/5% carbon dioxide atmosphere enhances the response of several rodent tumors. B6D2F1/J mice bearing Lewis lung tumors, measuring 50-100 mm3 were treated with 4, 8 and 12 ml/kg of Fluosol-DA intravenously each morning. Three Gy fractions twice per day were employed and carbogen breathing was maintained 1 hr prior to and during each X ray treatment. The dose modifying factors were 1.42 +/ 0.16 at 4 ml/kg, 1.85 +/- 0.23 at 8 ml/kg, and 2.17 +/- 0.34 at 12 ml/kg. In a second experiment, a single dose of Fluosol-DA (12 ml/kg) was administered on day 1 to B6D2F1/J male mice, bearing established subcutaneous Lewis lung tumors, as described above. X rays were delivered in 2, 3, or 4 Gy fractions once per day for five days. The dose modifying effect was 2.60 +/- 0.54. The effect of this treatment program was the same as that seen with single dose radiation. These experiments demonstrate that Fluosol-DA need not be administered with every fraction to produce an improved treatment outcome with fractionated X rays. PMID- 3093416 TI - Reactions of tumors and normal tissues in mice to irradiation in the presence and absence of a perfluorochemical emulsion. AB - The effect of pre-treatment with the perfluorochemical emulsion, Fluosol-DA, on the radiation response of normal tissues and EMT6 mammary tumors in BALB/c mice was examined. Pre-treating tumor-bearing mice with .015 ml/g of Fluosol and 30 min of carbogen (95% O2/5% CO2) increased the number of tumor cells killed by irradiation with doses of 2.5-20 Gy; the change in the radiation dose-response curve was consistent with a reduction in the hypoxic fraction. Fluosol did not alter the response of tumors in air-breathing or N2-asphyxiated mice and carbogen alone did not alter the radiation response of this tumor significantly. Carbogen treatments 5-60 min in duration produced similar enhancements of tumor radiosensitivity in Fluosol-treated animals. Pre-treatment with Fluosol plus carbogen also increased the number of tumor cells killed by a fractionated regimen of four 2.5 Gy fractions given over 2 days. Pre-treatment with Fluosol-DA plus carbogen, therefore, increased the antineoplastic effects of radiotherapy in both single-dose and multi-fraction radiation regimens. In contrast, Fluosol did not increase the effect of radiation on the partially committed (CFU-GM) or pluripotent (CFU-S) stem cells of the bone marrow or on the CFU-GM of the spleen. The radiation response of the skin was only slightly enhanced by pre-treatment with Fluosol plus carbogen. These data show that treatment of mice with perfluorochemical emulsions plus carbogen can produce therapeutic gain by improving the radiation response of solid tumors, without producing an equivalent increase in the radiation response of potentially dose-limiting normal tissues. These findings encourage further evaluations of these agents as adjuncts to clinical radiotherapy. PMID- 3093417 TI - Choice of optimum megavoltage for accelerators for photon beam treatment. AB - Over three decades ago, the development of megavoltage accelerators revolutionized radiation oncology and provided the therapist with photons and electrons of any desired energy. The initial advantages cited for high energy photon therapy, listed below, have proved valid and accelerators have almost totally replaced orthovoltage units. Initially, it appeared that most of these cited advantages should continue to improve with increasing energy, and there has been an impetus for the production of ever higher megavoltage accelerators. Some of these advantages are reviewed in this paper. Also, recent investigations have indicated increasing diffuseness of the photon beam boundary with increasing energy because of lateral transport of electrons. The impact on treatment planning as a function of energy of the increase in volume dose due to the diffuseness of beam boundaries, "build-down" and "rebuild-up" effects in tissues at cavity and inhomogeneity interfaces, bone absorption, and photoneutron production are discussed. Consideration of the behavior of these parameters indicates that optimum photon energies have been achieved and that the impetus for higher megavoltages is unwarranted for most treatment. For many therapeutic applications, there are major advantages of 4 MV to 8 MV photon beams relative to 60Co gamma rays. For large lesions in the abdomen or pelvis there is an advantage to energies above those provided by 15 MV units. The various considerations above are discussed and summarized as a function of lesion site and megavoltage. PMID- 3093418 TI - Trends in radiation therapy demographics--1974 to 1983. PMID- 3093419 TI - Spinal cord protection during radiation therapy. AB - Treating intrathoracic malignancies to high doses, particularly those of lung and esophagus, requires limiting the radiation dose delivered to the spinal cord. Several factors are important in determining the cord dose. These are: The distance from the block or collimator edge to the cord, the variation of dose with distance from the block or collimator edge and, the expected variation of this distance for clinical set-up from day-to-day. When treating with an oblique beam, the position of the cord may be difficult to identify. A technique for localizing the spinal cord on a simulator film at an arbitrary gantry angle is presented. The technique requires determination of distances from the central axis of the beam to the medial aspect of the pedicle and posterior vertebral body. These can readily be obtained from measurements on orthogonal, AP/PA and lateral isocentric simulator radiographs. A mathematical transformation is applied to determine the corresponding cord locations on the oblique radiographs for any arbitrary gantry angle. The accuracy of cord localization was within 2-3 mm with a precision of 2 mm for five physicians who used this technique. The beam edge characteristics for 60Co, 6 MV, and 10 MV teletherapy unit were measured for various depths and field sizes. For the 6 and 10 MV units, the beam penumbra is nearly independent of the field size, depth and field defining devices (inner and outer collimator jaws, trimmer bars, and shielding blocks). Because the beam penumbra is dependent on the design of the linear accelerator, its measurement should be made individually for each linear accelerator. Our preliminary data on patient positioning uncertainty did not exceed the 6-8 mm limit documented in the literature. PMID- 3093420 TI - What's the optimum choice? PMID- 3093421 TI - Rearrangement of the c-myc gene in two giant cell carcinomas of the lung. AB - The c-myc oncogene was found to be rearranged in a human cell line of giant cell carcinoma of the lung (C-Lu65) and in a human primary giant cell carcinoma of the lung (LuC38C). The rearrangements in C-Lu65 and LuC38C were in regions about 7.5 kb and 6 kb, respectively, upstream from the transcription initiation site. No rearrangement of the c-myc gene was observed in a non-cancerous portion (LuC38N) of the lung of the patient who carried LuC38C. These results suggest that rearrangement of the c-myc gene may play some role in tumorigenesis of giant cell carcinoma of the lung. PMID- 3093422 TI - Induction of ornithine decarboxylase activity in rat glandular stomach mucosa by bile acids. AB - A single oral instillation of 1.5 g/kg body weight of sodium taurocholate resulted in a rapid, transient stimulation of ornithine decarboxylase activity in rat glandular stomach mucosa, reaching a peak (10 times the control value) 4 to 6 hr after sodium taurocholate treatment and returning to the control level within 48 hr. The degree of stimulation was dose-dependent. Sodium taurodeoxycholate and sodium taurochenodeoxycholate stimulated the enzyme activity similarly. PMID- 3093423 TI - Cumulative incidence rates for Hodgkin's disease and other hematologic malignancies, with special reference to age-related carcinogenesis. AB - The cumulative incidence rate throughout the life span was analyzed for 4,865 Hodgkin's disease cases, in comparison with 16,015 malignant lymphomas (ML), 1,694 acute lymphocytic leukemias (ALL), 3,967 acute myeloid leukemias (AML), 2,109 chronic myeloid leukemias (CML), and 4,752 chronic lymphoid leukemias (CLL) in US white reported in the SEER program during 1973-1981. A log-linear increase was observed in ML, AML, CML, and CLL throughout the life-span, but only in childhood in ALL. Hodgkin's disease showed a steep increase until age 20-24, and then the increase became much more gradual. The cumulative incidence rates for males and females were parallel for ML and leukemias, but diverged for Hodgkin's disease (the rate for females had a lower slope than that for males after age 20 24). This difference was mainly caused by a lower frequency in females of mixed cellularity and lymphocyte predominance subtypes. The incidence curve of Hodgkin's disease was consistent with the two-stage model of carcinogenesis; it is likely that the proliferation of progenitor cells peaks at a young age and that the death rate of so-called intermediate cells is a primary influence during the subclinical stage. The cytogenesis of Hodgkin's disease and the histologic variation with special reference to the T-zone histiocytes suggest that a strong host defense mechanism against neoplastic change is involved, rather than different etiologic influences. PMID- 3093424 TI - Fumaric acid enhances DNA synthesis of rat hepatocytes by counteracting the toxicities of mitomycin C and aflatoxin B1. AB - The effect of fumaric acid was examined on DNA synthesis in hepatocytes or hepatoma cells from rats treated with toxic agents. Male Donryu rats were injected with mitomycin C or aflatoxin B1, singly or in combination with fumaric acid. After a specified period, hepatocytes were isolated from the liver by the collagenase perfusion method and placed in culture, and their activities for DNA synthesis were measured. The iv injection of rats with mitomycin C (0.5 mg/kg) reduced the semiconservative DNA synthesis of the hepatocytes, but simultaneous dosing of fumaric acid (40 mg/kg) enhanced the recovery of the DNA synthesis. The DNA synthesis of hepatoma cells, a 3'-methyl-4-(dimethylamino)azobenzene-induced transplantable cell line growing in the abdominal ascites of rats, was also reduced by the iv injection of mitomycin C but, in contrast to that of the hepatocytes, was little influenced by the simultaneous dosing of fumaric acid. The ip injection of fumaric acid also reduced the toxicity of aflatoxin B1 (0.25 mg/kg, ip), preventing the reduction of DNA synthesis as well as the occurrence of nuclear degenerative changes in the aflatoxin B1-exposed hepatocytes. PMID- 3093425 TI - Antitumor effect of recombinant human interleukin 1 alpha against murine syngeneic tumors. AB - Interleukin 1 (IL1) has been suggested to have antitumor activity but there is no clear-cut evidence of an in vivo antitumor effect of pure IL1. In this work, the antitumor effect of purified recombinant human IL1 alpha (rHu-IL1 alpha) was assessed on murine tumors transplanted intradermally in syngeneic female mice. rHu-IL1 alpha inhibited the growth of Meth A sarcoma in BALB/c mice, B16 melanoma in C57BL/6 mice and colon 26 adenocarcinoma in CDF1 mice, as well as the spontaneous pulmonary metastasis of Lewis lung carcinoma in BDF1 mice, at intratumoral (itu), intramuscular (im), and/or intravenous (iv) doses ranging from 1 to 30 micrograms/mouse. The antitumor effect of rHu-IL1 alpha was generally dose- and route-dependent, being highest by the itu route, followed by the im and iv routes in that order. Palpable 7-day-old Meth A sarcoma was completely regressed in some mice given rHu-IL1 alpha itu once at doses of 10-30 micrograms/mouse (cured ratio; 71-100%), once a day for 3 days at doses of 3-30 micrograms/mouse (57-86%) or once a day for 7 days at doses of 1-10 micrograms/mouse (14-100%). Palpable 7-day-old B16 melanoma was also regressed completely in some mice given seven itu doses of 10-30 micrograms/mouse (14-86%). One-day-old Meth A sarcoma was more sensitive to rHu-IL1 alpha than 7-day-old Meth A sarcoma. There was no macroscopic sign of inflammation at the site of injection of rHu-IL1 alpha. These results show that rHu-IL1 alpha has antitumor activity in vivo and is worthy of further study as a potential antitumor agent. PMID- 3093427 TI - Justification of conservative surgical treatment of childhood thyroid cancer: report of eleven cases and analysis of Japanese literature. AB - Eleven thyroid carcinoma patients of 15 years old and under are reported. They represent only 1.3% of our personal series of 861 thyroid carcinoma cases. One case died from undifferentiated carcinoma of the thyroid. However, the other 10 cases of papillary or follicular carcinoma are all alive, in spite of the apparently advanced stage of the disease at the time of operation in most of the cases. From our experience and analysis of 127 cases of childhood thyroid cancer reported in the Japanese literature, it is suggested that childhood thyroid cancer constitutes an extreme case of thyroid cancer occurring in the adolescent and young adult periods, and that rather conservative surgical treatment, avoiding total laryngectomy, and preserving the recurrent laryngeal nerve and the parathyroid glands as far as possible, usually suffices for treatment. In these Japanese cases, radiation did not appear to have been an important causative factor of childhood thyroid cancer. PMID- 3093426 TI - Inhibitory effect of murine recombinant interferon (beta) on the pulmonary metastasis of B-16 melanoma. AB - The antitumor effect of murine recombinant interferon (beta) [Mu-rIFN(beta)] was examined on artificial metastasis of B-16 melanoma in C57BL/6 mice. The numbers of pulmonary nodules were significantly decreased to 16.7 +/- 4.7 (P less than 0.01), 9.5 +/- 4.2 (P less than 0.01), 7.1 +/- 5.6 (P less than 0.01) in mice given 20,000 units of Mu-rIFN(beta) intraperitoneally (ip) 24, 6, and 3 hr before intravenous tumor inoculation, respectively, compared with the control group of mice (57.1 +/- 1.4), if B-16 melanoma cells (5 X 10(5] were intravenously injected 28 days before the experiment. In mice given 20,000 units of Mu rIFN(beta) ip 24, 6, and 3 hr before the experiment, the natural killer (NK) activities of spleen cells against YAC-1 cells were elevated to 45.5 +/- 6.1%, 53.7 +/- 3.4%, 43.2 +/- 6.5%, respectively, compared with NK activities in control mice (20.3 +/- 3.1%). Similarly, NK activities against B-16 melanoma cells were also elevated in mice given Mu-rIFN(beta). Pretreatment with anti asialo GM1 antibody and carrageenan reduced the inhibitory effect of Mu rIFN(beta) on the pulmonary metastasis. In vitro colony inhibition of more than 50% was not observed even if B-16 melanoma cells were incubated with 100,000 units/ml of Mu-rIFN(beta). From these results, it can be concluded that the inhibition of pulmonary metastasis by Mu-rIFN(beta) is mediated via host defense mechanisms and that NK cells and macrophages are both important for the inhibition. PMID- 3093428 TI - The active immunotherapy of a 3-methylcholanthrene-induced rat tumor with Friend virus-infected (xenogenized) tumor cells. AB - We investigated the various conditions necessary for potentiating the immunogenicity of viable Friend virus (FV)-infected rat fibrosarcoma KMT-17 cells. The immunogenicity was most potent among cells passaged through three generations of FV-tolerant rats; a single subcutaneous immunization induced an increase in the transplantation resistance (LTD50) of 10,000 or more. It was also found that intradermal immunization of the tumor cells induced stable and potent resistance to the transplantation of non-xenogenized tumor cells soon after immunization, and that irradiated non-xenogenized tumor cells were effective in supplying booster immunization. Active immunotherapy against KMT-17 cells pre transplanted subcutaneously was carried out on the basis of the above findings with the results that the active anti-tumor immunization alone caused a complete regression in 30% of the tumor-burdened rats. These findings indicate the possibility of achieving active immunotherapy with xenogenized tumor cells. PMID- 3093429 TI - The role of anti-asialo GM1 antibody-sensitive cells in the implementation of tumor-specific T cell-mediated immunity in vivo. AB - The present study deals with the role of cells sensitive to anti-asialo GM1 antibody treatment in T cell-mediated tumor cell eradication in vivo. Rabbit anti asialo GM1 antiserum was injected into C3H/He mice. This treatment not only resulted in almost complete abrogation of natural killer (NK) cell activity but also produced a potent inhibiting effect on the generation of activated macrophage activity induced by inoculating Propionibacterium acnes (P. acnes). Such an immunodepressed state lasted for 20 days or more after 5 consecutive injections of anti-asialo GM1 antiserum. These anti-asialo GM1 antibody-treated C3H/He mice were used as recipients in Winn assays, in which the neutralizing activity of spleen cells immunized to syngeneic X5563 tumor cells was assessed. The results demonstrated that anti-X5563 immune spleen cells depleted of asialo GM1-positive cells by the in vitro treatment with anti-asialo GM1 antibody plus complement exhibited potent anti-X5563 tumor-neutralizing activity in antibody untreated normal recipient mice. In contrast, the X5563-immune spleen cells depleted of asialo GM1+ cells failed to produce tumor protection in asialo GM1 antiserum-treated recipient mice. When T cell-deprived B cell mice were used as recipients in Winn assays, X5563 immune spleen cells depleted of asialo GM1+ cells exhibited or failed to exhibit tumor-neutralizing activity in asialo GM1 antiserum-untreated or -treated recipient B cell mice, respectively. These results indicate that the implementation of T cell-mediated in vivo protective immunity requires the participation of anti-asialo GM1 antibody-sensitive cells, but not necessarily the host's T cells. PMID- 3093431 TI - Semi-synthesis of A23187 (calcimycin) analogs. III. Modification of benzoxazole ring substituents, ionophorous properties in an organic phase. AB - Ten semi-synthetic analogs of A23187 (calcimycin), with only the benzoxazole ring substituents modified together with the ionophore X14885A were studied with regard to their calcium and magnesium carrier properties through an organic phase (toluene - butanol, 70:30). The results indicate that the carboxylic group and the oxazolic nitrogen, maintained in the ortho position are essential for the ionophorous properties. Further, the introduction of a substituent in place of the NHCH3 group, producing steric hindrance of the carboxylic group leads to a destabilization of the 2:1 associations with cations. PMID- 3093430 TI - Fengycin--a novel antifungal lipopeptide antibiotic produced by Bacillus subtilis F-29-3. AB - Fengycin is an antifungal lipopeptide complex produced by Bacillus subtilis strain F-29-3. It inhibits filamentous fungi but is ineffective against yeast and bacteria. The inhibition is antagonized by sterols, phospholipids and oleic acid, whereas two other unsaturated fatty acids increase the antifungal effect. Fengycin consists of two main components differing by one amino acid exchange. Fengycin A is composed of 1 D-Ala, 1 L-Ile, 1 L-Pro, 1 D-allo-Thr, 3 L-Glx, 1 D Tyr, 1 L-Tyr, 1 D-Orn, whereas in fengycin B the D-Ala is replaced by D-Val. The lipid moiety of both analogs is more variable, as fatty acids have been identified as anteiso-pentadecanoic acid (ai-C15), iso-hexadecanoic acid (i-C16), n-hexadecanoic acid (n-C16), and there is evidence for further saturated and unsaturated residues up to C18. PMID- 3093432 TI - Semi-synthesis of A23187 (calcimycin) analogs. IV. Cation carrier properties in mitochondria of analogs with modified benzoxazole rings. Antimicrobial activity. AB - The transporting abilities in the mitochondrial membrane for Ca++ and Mg++ of ten semi-synthetic analogs A23187 (calcimycin) and X14885A are compared. Analogs classified as efficient divalent cation carrier retained the calcimycin antimicrobial activity against three Gram-positive strains tested. PMID- 3093434 TI - Studies on lipoxygenase inhibitors. II. KF8940 (2-n-heptyl-4-hydroxyquinoline-N oxide), a potent and selective inhibitor of 5-lipoxygenase, produced by Pseudomonas methanica. AB - Pseudomonas methanica KY4634 was found to produce 5-lipoxygenase inhibitor designated KF8940, MY12-62a and MY12-62c. The inhibitors were purified by solvent extraction, silica gel column chromatography, reversed-phase low pressure liquid chromatography and crystallization. The chemical structures of KF8940, MY12-62a and MY12-62c were determined to be 2-n-heptyl-4-hydroxyquinoline-N-oxide, 2-n heptyl-4-hydroxyquinoline and 3-n-heptyl-3-hydroxy-1,2,3,4-tetrahydroquinoline 2,4-dione, respectively, on the basis of their physico-chemical properties. Among them, KF8940 was the most potent inhibitor. The compound inhibited 5-lipoxygenase of rat basophilic leukemia cells in a dose-dependent manner and the half maximal inhibitory concentration (IC50) was 1.5 X 10(-7) M. At this concentration, KF8940 did not inhibit bovine platelet 12-lipoxygenase and cyclooxygenase, and the IC50 values for these enzyme were 3.5 X 10(-5) M and 1.7 X 10(-4) M, respectively. The results indicated that KF8940 is a potent and selective inhibitor of 5 lipoxygenase. The IC50 value of MY12-62c for 5-lipoxygenase was 1.9 X 10(-5) M and that of MY12-62a was 1.9 X 10(-5) M. PMID- 3093433 TI - Ahpatinins, new acid protease inhibitors containing 4-amino-3-hydroxy-5 phenylpentanoic acid. AB - A soil isolate, Streptomyces sp. WK-142, was found to produce new acid protease inhibitors, ahpatinins A, B, D, E, F and G active against pepsin and renin. Ahpatinin C was found to be identical with pepstatin A. The structure determinations were based on mass spectral data. Four of the compounds contain the unusual amino acid, 4-amino-3-hydroxy-5-phenylpentanoic acid as a building component. PMID- 3093435 TI - Enhancement of graft-versus-host reaction and delayed cutaneous hypersensitivity in mice by ubenimex. AB - The effect of ubenimex on graft-versus-host reaction and delayed cutaneous hypersensitivity in mice was studied. Ubenimex enhanced the graft-versus-host reaction in a dose range from 0.005 to 0.5 mg/kg. Ubenimex inhibited the aging caused decrease of delayed cutaneous hypersensitivity to oxazolone and the efficacy was greater with older mice. Ubenimex also inhibited mitomycin C and L1210-caused decreases of delayed cutaneous hypersensitivity to picryl chloride. However, the excess decrease caused by mitomycin C was not significantly altered by ubenimex. PMID- 3093436 TI - Changes in metabolic and reproductive characteristics associated with lactation and glucose infusion in the postpartum ewe. AB - This study examined mechanisms whereby the metabolic environment interacts with basic reproductive function. Ewes lambing during the breeding season were fed to maintain (MAINT, n = 10) or gain (GAIN, n = 11) body weight during the last 4 mo of gestation. From d 7 to 22 postpartum, ewes were infused iv with saline (n = 10) or glucose at a rate calculated to increase normal glucose entry rate by 75% (n = 11). Blood samples were collected daily to determine plasma concentrations of nutritive metabolites and insulin and at frequent intervals on d 14 and 21 to determine serum gonadotropin concentrations. Hypothalami and pituitaries were collected on d 22 to determine hormone content and receptor concentrations. Plasma concentrations of nutritive metabolites and insulin indicated that MAINT ewes mobilized more (P less than .01) body fat and protein reserves during gestation and early lactation than ewes in the GAIN group. Glucose infusion elevated plasma concentrations of glucose (P less than .05) and insulin (P less than .07) and reduced (P less than .05) fat and protein mobilization, even though it depressed feed intake (P less than .001), compared with saline infusion. Hypothalamic gonadotropin-releasing hormone (GnRH), pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) content and pituitary GnRH receptor concentration were similar between treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093437 TI - Ovarian compensatory hypertrophy following unilateral ovariectomy in the suckled sow. AB - The effects of unilateral ovariectomy on ovarian compensatory hypertrophy (OCH), endocrine profiles and the pituitary response to gonadotropin releasing hormone (GnRH) were studied in 46 multiparous suckled sows. On d 20 of lactation (d 0 of experiment), sows were subjected to sham ovariectomy (Sham; n = 23) or unilateral ovariectomy (ULO; n = 23). On d 1 (n = 16), 2 (n = 15) or 8 (n = 15) following initial surgery the remaining ovaries in both Sham and ULO sows were removed. Immediately following removal of the remaining ovaries, GnRH (10 micrograms) was administered to each sow. Peripheral blood samples were taken every 10 min for 80 min beginning 20 min prior to GnRH administration. No difference in ovarian weight was observed between ULO and Sham sows until d 8, when ovarian weight was greater (P less than .05) for the remaining ovary from ULO sows (3.96 +/- .21 vs 5.91 +/- .39 g). Ovarian follicular fluid weights from ULO sows were greater (P less than .05) than Sham sows on both d 2 and 8. On d 1, plasma concentrations of follicle stimulating hormone (FSH) were greater (P less than .05) in ULO sows than in Sham sows (2.9 +/- .2 vs 2.1 +/- .1 ng/ml). Plasma FSH concentrations, however, did not differ between Sham and ULO sows on either d 2 or 8. Ovarian venous concentrations of estradiol-17 beta were also greater (P less than .05) in ULO sows compared with Sham sows on d 2 but not d 8. PMID- 3093438 TI - Concentrations of prolactin, luteinizing hormone and follicle stimulating hormone in pituitary and serum of horses: effect of sex, season and reproductive state. AB - Pituitary and serum from 86 male or female horses of various reproductive states were collected in the normal breeding season (summer) and in the nonbreeding season (winter) at a commercial slaughterhouse. Concentrations of prolactin (PRL), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by radioimmunoassay. Concentrations of pregnant mare serum gonadotropin and reproductive steroids in serum and gross appearance of the reproductive tract and gonads were used to catagorize reproductive state. Concentrations of PRL were higher (P less than .01) in summer than in winter in pituitary and serum of mares, stallions and geldings. In summer, mares had higher (P less than .01) concentrations of PRL in serum than stallions. In mares, concentrations of LH in pituitary were higher (P less than .05) in summer than in winter. Concentrations of LH in serum were higher (P less than .01) in summer than in winter in mares and geldings, higher (P less than .01) in mares than in stallions in summer, higher (P less than .01) in geldings than in stallions in summer and higher (P less than .01) in mares with low serum progesterone (P) concentrations than in mares with high P concentrations in summer. Concentrations of FSH in pituitary and serum did not differ between summer and winter for any type of horse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093439 TI - Growth of salmonellas in different enrichment media. AB - The usefulness of selenite-F (S-F), tetrathionate (MKT) and Rappaport-10 (R-10) broths as enrichment media to support growth of salmonellas either alone or in the presence of other competing organisms was studied. Their ability to support the growth of stressed salmonellas from water was also investigated. It was observed that R-10 was more inhibitory to competing organisms than MKT and S-F. It strongly inhibited the growth of Pseudomonas aeruginosa, Citrobacter freundii and Proteus vulgaris though not of Escherichia coli and Enterobacter aerogenes. It was more toxic, however, to small numbers of salmonellas than MKT and S-F. Tetrathionate was strongly inhibitory for E. coli and Ent. aerogenes but much less so for Proteus and Pseudomonas species. Selenite-F was much less inhibitory than MKT to Ps. aeruginosa and it did not inhibit growth of E. coli and Ent. aerogenes as much as MKT. Salmonellas were inhibited by all three enrichment media and none of them is ideally suited for direct use. Of the three media, R-10 was much more inhibitory to stressed organisms than S-F or MKT. PMID- 3093440 TI - Numerical taxonomy of proteolytic psychrotrophs from Queensland raw milks. AB - Eighty-seven proteolytic psychrotrophic micro-organisms were isolated from 11 bulk milk supplies of two Queensland factories from different climatic regions, before and after storage at 4 degrees C for 7 d. These isolates together with 15 reference strains formed the basis of a numerical taxonomic study involving 81 attributes. All but six isolates were pseudomonads. The strains clustered into nine groups, of which one group consisted of four yeasts. One group, containing 39 isolates, was designated as Pseudomonas fluorescens biovar 1; three groups, containing 27 isolates, as Ps. fluorescens biovar 5; and one group, containing 10 isolates, as Ps. putida biovar A. This study showed that the proteolytic psychrotrophic microflora of the 11 milks supplying the two factories was substantially different and that the proteolytic flora of 7 d refrigerated milk could not be estimated by examining the flora before storage. PMID- 3093441 TI - Kinetics of the tuberculocidal response by alkaline glutaraldehyde in solution and on an inert surface. AB - Single cell suspensions of BCG and Mycobacterium tuberculosis were exposed to 2% alkaline glutaraldehyde solution (pH 8.0) and the rate of kill measured at intervals up to 30 min. Residual glutaraldehyde was neutralized with freshly prepared 1% sodium bisulphite. The rate of kill was directly proportional to the temperature and independent of the inoculum size whether the organism was tested in suspension or attached to an inert surface. Glutaraldehyde was slightly more bactericidal for the virulent M. tuberculosis than for the attenuated BCG. A substantial proportion of the mycobacterial population on an inert surface floated off during its exposure to the glutaraldehyde solution but the 'floaters' were killed at an equivalent rate to the attached bacilli. Complete sterility of a standardized suspension of M. tuberculosis could not be achieved within the 10 min period specified by the tuberculocidal assay, although it was usually attained within 20 min. PMID- 3093442 TI - Resistance of enterococci to antibiotic combinations. PMID- 3093443 TI - Antimicrobial prophylaxis in low-risk biliary surgery. PMID- 3093444 TI - Susceptibility of Pseudomonas aeruginosa strains isolated from hospitalized children. AB - Pseudomonas aeruginosa strains, 1285 in total, were isolated from hospitalized children in the period 1981-1984. Serotypes 011 and 06 and nontypable strains were the most frequently identified. 44.6% of serotype 011 strains and between 12.4 and 37.7% of other serotypes were resistant to gentamicin, or carbenicillin, or both agents. The aminoglycosides with the highest activity against P. aeruginosa isolates were amikacin and netilmicin. Among the seven beta-lactam antibiotics tested the most active were cefsulodin, piperacillin and azlocillin. PMID- 3093445 TI - Ciprofloxacin, azlocillin, ceftizoxime and amikacin alone and in combination against gram-negative bacilli in an infected chamber model. AB - Ciprofloxacin, azlocillin, ceftizoxime, and amikacin were studied alone and in combination against six Enterobacteriaceae and six strains of Pseudomonas aeruginosa in an infected chamber model in rabbits simulating a closed space infection. In-vivo results were compared with in-vitro tests of inhibition, killing and synergy. Ciprofloxacin was the most effective single agent, with efficacy against five of the six Enterobacteriaceae when used in low doses, and two of the six pseudomonads when used in high doses. The development of in-vitro resistance to ciprofloxacin was observed during therapy in strains which failed to be eradicated. Ciprofloxacin and azlocillin together was the most effective regimen, with efficacy against eleven of the twelve strains. Synergy, as determined by chequerboard testing, did not correlate with in-vivo outcome. Unlike mezlocillin, azlocillin, ceftizoxime or amikacin, MIC testing of ciprofloxacin was predictive of in-vivo success. PMID- 3093446 TI - Beta-lactam antibiotics and mycobacteria. PMID- 3093447 TI - In-vitro activity of Sch 34343, a new penam, against gram-positive isolates from cancer patients. AB - The in-vitro activity of Sch 34343, a new penam antibiotic, was tested against 257 Gram-positive isolates from cancer patients, and compared with that of imipenem and amifloxacin. Sch 34343 was extremely active against beta-haemolytic streptococci (Lancefield groups A, B and G) with MIC90s ranging from 0.025 to 0.05 mg/l. It was also active against methicillin-susceptible Staphylococcus aureus and had variable activity against coagulase-negative staphylococci. MIC90 for Listeria monocytogenes was 0.78 mg/l and 84% of enterococcal isolates were inhibited by 6.25 mg/l. PMID- 3093448 TI - Trimethoprim in enteric fever. AB - Seventy-one patients suffering from typhoid or paratyphoid fever were treated with trimethoprim. Sixty-three were cured. Only three patients continued to excrete Salmonella typhi in stools at the time of discharge from hospital. Trimethoprim alone is a suitable agent for the treatment of enteric fever. PMID- 3093449 TI - Sub MIC levels of cefoxitin and imipenem affect disc diffusion zone diameters to cefotaxime, ceftazidime, piperacillin and imipenem for Pseudomonas aeruginosa. PMID- 3093451 TI - Influence of the ventral surface of the medulla on tracheal responses to CO2. AB - These studies investigated the role of the intermediate area of the ventral surface of the medulla (VMS) in the tracheal constriction produced by hypercapnia. Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. Airway responses were assessed from pressure changes in a bypassed segment of the rostral cervical trachea. Hyperoxic hypercapnia increased tracheal pressure and phrenic nerve activity. Intravenous atropine pretreatment or vagotomy abolished the changes in tracheal pressure without affecting phrenic nerve discharge. Rapid cooling of the intermediate area reversed the tracheal constriction produced by hypercapnia. Graded cooling produced a progressive reduction in the changes in maximal tracheal pressure and phrenic nerve discharge responses caused by hypercapnia. Cooling the intermediate area to 20 degrees C significantly elevated the CO2 thresholds of both responses. These findings demonstrate that structures near the intermediate area of the VMS play a role in the neural cholinergic responses of the tracheal segment to CO2. It is possible that neurons or fibers in intermediate area influence the motor nuclei innervating the trachea. Alternatively, airway tone may be linked to respiratory motor activity so that medullary interventions that influence respiratory motor activity also alter bronchomotor tone. PMID- 3093450 TI - Effect of cyclooxygenase inhibition on ethchlorvynol-induced acute lung injury in dogs. AB - In anesthetized dogs ethchlorvynol (ECV, 9 mg/kg) was selectively administered into the right pulmonary circulation to produce unilateral acute lung injury (ALI) characterized by nonhydrostatic pulmonary edema and systemic hypoxemia. To investigate the hypothesis that products of cyclooxygenase activity are mediators of the arterial hypoxemia, but not the edema formation in this injury, animals were pretreated with one of two chemically dissimilar cyclooxygenase inhibitors, indomethacin (5 mg/kg), or ibuprofen (12.5 mg/kg), or vehicle (0.1 M sodium carbonate) prior to the administration of ECV. Pretreatment with either inhibitor prevented the ECV-induced systemic hypoxemia observed in animals pretreated with vehicle (P less than 0.01). Despite this protection of systemic oxygenation, there was no redistribution of blood flow to the uninjured lung following unilateral ECV administration. Cyclooxygenase inhibition prior to ALI did not attenuate the accumulation of lung water. In the ibuprofen group, left atrial pressure increased significantly following ECV administration. We conclude that a product(s) of cyclooxygenase-mediated arachidonic acid metabolism is responsible for the altered vascular reactivity and consequent systemic hypoxemia in this model, but that the edema formation following ECV is not related to cyclooxygenase activity. In addition, ibuprofen, administered prior to the induction of ALI, exhibits properties not shared by indomethacin but is not different in its capacity to attenuate hypoxemia or in its failure to limit edema formation. PMID- 3093452 TI - Measurement of CO2 production by the doubly labeled water technique. AB - Recent applications of the doubly labeled water technique to the study of human metabolism have employed multiple sampling of body water over protracted periods, rather than the more traditional method of taking only an initial and final sample for isotopic analysis. In addition fractional turnovers of the body pools have been estimated by fitting curves to the sequential log-converted isotope enrichment against time. By manipulation of data collected in the field in a study of metabolism of vespertilionid bats, it is shown the curve-fitting technique results in an accurate estimate of CO2 production only when the rate of CO2 production is constant. Biologically realistic nonsteady-state conditions result in errors in estimates of CO2 production of up to 30%. In conditions where CO2 production is known to be temporally variable, the more traditional two sample method may provide a more accurate estimate of CO2 production. PMID- 3093453 TI - Diethyl pyrocarbonate (an imidazole binding substance) inhibits rostral VLM CO2 sensitivity. AB - Diethyl pyrocarbonate (DEPC) has been useful in vitro as an agent relatively specific for binding to imidazole of histidine. Administered via the cisterna magna DEPC inhibits central chemosensitivity in conscious rabbits, supporting the alphastat hypothesis for central chemoreceptor function. In this study I have applied DEPC via 1 X 3 mm cottonoid pledgets to each of the three ventrolateral medulla (VLM) chemosensitive areas in glomectomized, vagotomized, paralyzed, and servo-ventilated alpha-chloralose-urethan-anesthetized cats. CO2 responses measured by integrated phrenic nerve output were evaluated before and after DEPC application. A dose of 40 mmol/l applied to the rostral chemosensitive area increased the CO2 threshold (5.3%) and significantly decreased (P less than 0.03; Wilcoxon sign rank test) the initial slope (-43%) and the maximum (-41%) of the CO2 response. No significant effects were observed with DEPC application in the intermediate or caudal areas. Treatment with 40 mmol/l hydroxylamine immediately after DEPC in the rostral area prevented the effects supporting the interpretation that imidazole was the reactant with DEPC. The results are consistent with the hypothesis that imidazole-histidine is involved in the mechanism of central chemoreception and indicate that only the rostral area utilizes a DEPC inhibitable mechanism. PMID- 3093454 TI - CSF acid-base regulation and ventilation in iso- and hypocapnic Hacetate acidosis. AB - Intravenous infusion in conscious rabbits of Hacetate decreases both arterial CO2 partial pressure PaCO2 and cerebrospinal fluid (CSF) HCO3- more than observed with HCl or HNO3 infusion. These acids did not affect CSF HCO3- in isocapnic conditions, and this study asks whether Hacetate infusion will do so. Arterial, central venous, and cisterna magna catheters were implanted in pentobarbital anesthetized rabbits and all subsequent measurements were performed in the conscious state. Hacetate was infused intravenously over 6 h to decrease plasma HCO3- the same amount in a group allowed to decrease its PaCO2 in response to the acid (hypocapnic) and one in which PaCO2 was maintained at control levels (isocapnic). CSF HCO3- decreased significantly in isocapnia, although the change was less than in hypocapnia. Stoichiometrically by 6 h the measured CSF HCO3- change was balanced by an increase in acetate in hypocapnia and the sum of an increase in acetate and a decrease in chloride in isocapnia. Mechanistically, net acetate entry into CSF appears to involve an exchange for chloride as proposed for NO3-/Cl- and a process that lowers CSF HCO3-. This process could be competitive replacement of HCO3- by acetate in the CSF production mechanism or nonionic diffusive entry of Hacetate into CSF with subsequent titration of HCO3-. The decreases in CSF HCO3- result from the acetate mechanism and the hypocapnic effect on Cl- and HCO3-. The greater ventilatory response results from the greater CSF acidification or a specific effect of acetate per se. PMID- 3093455 TI - Indomethacin and FPL-57231 inhibit antigen-induced airway hyperresponsiveness in sheep. AB - We compared the development of antigen-induced airway hyperresponsiveness (AHR) 24 h after challenge with Ascaris suum antigen in allergic sheep with acute (n = 7) and with dual (n = 7) airway responses and then attempted to modify this AHR. Cholinergic airway responsiveness was determined by measuring the carbachol dose required to increase specific lung resistance (sRL) 150% (i.e., PC150). Subsequently the sheep were challenged with antigen and sRL was measured at predetermined times to document the presence or absence of a late response. PC150 was redetermined 24 h later followed by bronchoalveolar lavage (BAL) to assess inflammation. Only dual responders developed AHR (PC150 decreased, P less than 0.05). There were no significant differences in BAL between the two groups. Six dual responders were then, on separate occasions (greater than or equal to 3 wk), pretreated with placebo, indomethacin (2 mg/kg iv), or a leukotriene antagonist, FPL-57231 (30 mg inhaled). Neither agent significantly affected the acute response to antigen. Only FPL pretreatment blocked the late response, but both agents blocked the antigen-induced AHR 24 h later. BAL at 24 h showed no significant differences. These results indicate that only dual responders develop AHR 24 h after antigen challenge. This AHR appears independent of the late increase in sRL or the severity of pulmonary inflammation. AHR appears to be sensitive to agents that interfere with the early release or actions of cyclooxygenase and lipoxygenase metabolites in dual responders. PMID- 3093456 TI - Pressure-volume behavior of the upper airway. AB - The study was performed to investigate the relationship between force generation and upper airway expansion during respiratory efforts by upper airway muscles. In 11 anesthetized dogs we isolated the upper airway (nasal, oral, pharyngeal, and laryngeal regions) by transecting the cervical trachea and sealing the nasal and oral openings. During spontaneous respiratory efforts the pressure within the sealed upper airway, used as an index of dilating force, decreased during inspiration. On alternate breaths the upper airway was opened to a pneumotachograph, and an increase in volume occurred, also during inspiration. Progressive hyperoxic hypercapnia produced by rebreathing increased the magnitude of change in pressure and volume. At any level of drive, peak pressure or volume occurred at the same point during inspiration. At any level of drive, volume and pressure changes increased with end-expiratory occlusion of the trachea. The force-volume relationship determined from measurements during rebreathing was compared with pressure-volume curves performed by passive inflation of the airway while the animal was apneic. The relationship during apnea was 1.06 +/- 0.55 (SD) ml/cmH2O, while the force-volume relationship from rebreathing trials was -1.09 +/- 0.45 ml/cmH2O. We conclude that there is a correspondence between force production and volume expansion in the upper airway during active respiratory efforts. PMID- 3093457 TI - Distribution of cyclooxygenase products with cyclooxygenase inhibition in isolated dog lung. AB - Arachidonic acid metabolism can lead to synthesis of cyclooxygenase products in the lung as indicated by measurement of such products in the perfusate of isolated lungs perfused with a salt solution. However, a reduction in levels of cyclooxygenase products in the perfusate may not accurately reflect the inhibition of levels of such products as measured in lung parenchyma. We infused sodium arachidonate into the pulmonary circulation of isolated dog lungs perfused with a salt solution and measured parenchymal, as well as perfusate, levels of 6 keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), and thromboxane B2 (TxB2). These studies were repeated with indomethacin (a cyclooxygenase enzyme inhibitor) in the perfusate. We found that indomethacin leads to a marked reduction in perfusate levels of PGF2 alpha, PGE2, 6-keto-PGF1 alpha, and TxB2, as well as a marked reduction in parenchymal levels of 6-keto-PGF1 alpha and TxB2 when parenchymal levels of PGF2 alpha and PGE2 are not reduced. We conclude that, with some cyclooxygenase products, a reduction in levels of these products in the perfusate of isolated lungs may not indicate inhibition of levels of these products in the lung parenchyma and that a reduction in one parenchymal product may not predict the reduction of other parenchymal products. It can be speculated that some of the physiological actions of indomethacin in isolated lungs may result from incomplete or selective inhibition of synthesis of pulmonary cyclooxygenase products. PMID- 3093458 TI - Low testosterone syndrome in acutely ill adult males. PMID- 3093459 TI - [Economic analysis of a body x-ray scanning unit]. PMID- 3093460 TI - Structural studies on lipoteichoic acids from four Listeria strains. AB - The lipoteichoic acids were isolated from phenol extracts of four Listeria strains representing serotypes 4a, 4b, 6a, and 6 to compare the differences in structure of amphiphilic polysaccharides from various serotypes of Listeria spp. The lipoteichoic acids from the four strains examined had the same structure in both hydrophilic chains and lipid portions. On the basis of the results of nuclear magnetic resonance spectroscopy and Smith degradation, the hydrophilic chains were shown to be 1,3-linked poly(glycerol phosphate) in which some of the glycerol residues had alpha-galactosyl substituents. The lipid portions were released by treatment with 46% hydrogen fluoride or 98% acetic acid. They were determined to be 3(1)-(2'-O-alpha-D-galactopyranosyl-alpha-D-glucopyranosyl) 1(3), 2-diacylglycerol and 3(1)-[6'-phosphatidyl-2'-O-(alpha-D-galactopyranosyl) alpha- D-glucopyranosyl]-1(3),2-diacylglycerol. The degrees of glycosyl substitution and proportions of the two lipids varied to some extent among these four strains. PMID- 3093461 TI - Purification and characterization of phosphoenolpyruvate carboxylase from a cyanobacterium. AB - Phosphoenolpyruvate (PEP) carboxylase (EC 4.1.1.31) was purified 100-fold from the cyanobacterium Coccochloris peniocystis with a yield of 10%. A single isozyme was found at all stages of purification, and activity of other beta-carboxylase enzymes was not detected. The apparent molecular weight of the native enzyme was 560,000. Optimal activity was observed at pH 8.0 and 40 degrees C, yielding a Vmax of 8.84 mumol/mg of protein per min. The enzyme was not protected from heat inactivation by aspartate, malate, or oxalacetate. Michaelis-Menten reaction kinetics were observed for various concentrations of PEP, Mg2+, and HCO3-, yielding Km values of 0.6, 0.27, and 0.8 mM, respectively. Enzyme activity was inhibited by aspartate and tricarboxylic acid cycle intermediates and noncompetitively inhibited by oxalacetate, while activation by any compound was not observed. However, the enzyme was sensitive to metabolic control at subsaturating substrate concentrations at neutral pH. These data indicate that cyanobacterial PEP carboxylase resembles the enzyme isolated from C3 plants (plants which initially incorporate CO2 into C3 sugars) and suggest that PEP carboxylase functions anapleurotically in cyanobacteria. PMID- 3093462 TI - Membrane lipid composition of obligately and facultatively alkalophilic strains of Bacillus spp. AB - The membrane lipids from two obligately and two facultatively alkalophilic strains of Bacillus spp. were characterized in a comparative study that included B. subtilis. Preparations of membrane lipids were made from pH 10.5-grown cells of all of the alkalophiles and from pH 7.5- or 7.0-grown cells of the two facultative strains and B. subtilis. The two obligate alkalophiles contained high ratios of membrane lipid to membrane protein, and the lipid fraction contained a high proportion of neutral lipid. These characteristics are probably not prerequisites for growth at very high pH since one or another of the facultative strains failed to show these properties at high pH. All of the alkalophiles contained appreciable amounts of squalene and C40 isoprenoids. Among the polar lipids, the alkalophiles all contained high concentrations of anionic phospholipids, including phosphatidylglycerol and especially large amounts of cardiolipin; phosphatidylethanolamine was the other major phospholipid. Small amounts of bis(monoacylglycero)phosphate were found in most, but not all, of the alkalophile preparations. Glycolipids and phosphoglycolipids were absent. The fatty acid composition of the total phospholipid and individual fractions revealed two features that distinguished between the obligate and facultative strains. Membranes from the obligately alkalophilic species contained a high concentration of branched-chain fatty acids, comparable to that in membranes from B. subtilis, as well as a relatively high content of unsaturated fatty acids. By contrast, the facultatively alkalophilic strains contained almost no unsaturated fatty acids and a lower concentration of branched-chain fatty acids than either the obligate alkalophiles or B. subtilis. PMID- 3093464 TI - Immunologic distinctiveness of archaebacteria that grow in high salt. AB - The antigenic fingerprints of eight halophilic archaebacteria representing the groups recently outlined by molecular and chemical analyses were determined with calibrated antibody probes. Comparison with the antigenic fingerprints of methanogens encompassing all described families and most genera demonstrated that these two archaebacterial groups are themselves antigenically coherent but immunologically distinct. PMID- 3093463 TI - Control of developmental gene expression by cell-to-cell interactions in Myxococcus xanthus. AB - The ssbA mutants of Myxococcus xanthus behave as if they are unable to produce a cell-to-cell signal required for normal development. They are unable to form fruiting bodies or spores on developmental medium. They do sporulate, however, if allowed to develop in mixtures with wild-type cells. Fusions of developmentally induced promoters of M. xanthus to the Escherichia coli lacZ gene were used to characterize the effect of the ssbA mutations on developmental gene expression. Each of the five independent fusions tested was found to be dependent upon the ssbA+ allele for full expression. The ssbA mutants were able to express each of these fusions if the mutants were allowed to develop in mixtures with wild-type (Lac-) cells. These results cannot be explained on the basis of genetic exchange. The data are consistent with regulation of gene expression mediated by cell-to cell interactions. PMID- 3093465 TI - Occurrence of coenzyme F420 and its gamma-monoglutamyl derivative in nonmethanogenic archaebacteria. AB - Analysis of the fluorescent compounds extracted from six different species of halobacteria and one species each of Sulfolobus and Thermoplasma revealed the universal occurrence of coenzyme F420, (N-[N-[O-[5-(8-hydroxy-5-deazaisoalloxazin 10-yl)-2,3,4-trihydroxy -4-pentoxyhydroxyphosphinyl]-L-lactyl]-L-gamma-glutamyl] L -glutamic acid), or its gamma-monoglutamyl derivative or both. The total amount (approximately 100 pmol/mg [dry weight]) of these compounds found in the halobacteria studied was approximately 5% of the amount previously reported for methanogenic bacteria. The amount of F420 found in the Sulfolobus and Thermoplasma strains was approximately 1% of that found in the halobacteria. The major compound in all but one of the examined strains was the gamma-monoglutamyl derivative of F420; one strain of halobacteria contained only F420. For the halobacterium-derived samples, the additional glutamic acid was shown to be linked by a gamma-glutamyl peptide bond to the terminal glutamic acid of the F420 core structure by enzymatic hydrolysis of the samples with three different gamma glutamyltranspeptidases. The product of this enzymatic hydrolysis was F420 with one less glutamic acid in the side chain. PMID- 3093466 TI - Identification of pheromone-induced surface proteins in Streptococcus faecalis and evidence of a role for lipoteichoic acid in formation of mating aggregates. AB - The conjugative transfer of the Streptococcus faecalis plasmid pAD1 is characterized by a 10,000-fold increase in frequency following sex pheromone (cAD1) induction. Before the increase in plasmid transfer, donor cells synthesize a proteinaceous adhesin that facilitates the formation of mating aggregates. Four novel surface proteins appearing after exposure of pAD1-containing cells to sex pheromone have been identified. Thirty minutes after induction, a 130-kilodalton (kDa) protein was detectable by Western blotting. A 74-kDa protein, the major species present, and a pair of bands at 153 and 157 kDa were evident 45 min after induction. Induced cells containing another conjugative S. faecalis plasmid, pPD1, gave rise to three high-molecular-weight proteins of the same size (130, 153, and 157 kDa) as those synthesized by pAD1-containing cells. These proteins cross-reacted with antisera raised against induced cells containing pAD1. However, the major protein species produced by pPD1-containing cells had a molecular weight of 78,000 and did not cross-react significantly with the corresponding band of the pAD1 system. Pheromone-induced transfer of the two plasmids, when both were present in the same cell, was independent; induction was limited to the pheromone-specified plasmid. The possibility that lipoteichoic acid might act as a receptor (binding substance) for the induced adhesin protein was also explored. Free lipoteichoic acid (isolated from S. faecalis) inhibited clumping of induced cells, apparently by acting as a competitive inhibitor of the cellular binding substance. PMID- 3093467 TI - Gene for the alpha subunit of Bacillus subtilis RNA polymerase maps in the ribosomal protein gene cluster. AB - We isolated the gene encoding the alpha subunit of Bacillus subtilis RNA polymerase from a lambda gt11 expression vector library by using anti-alpha antibody as a probe. Four unique clones were isolated, one carrying a lacZ-alpha gene fusion and three carrying the entire alpha coding region together with additional sequences upstream. The identity of the cloned alpha gene was confirmed by the size and immunological reactivity of its product expressed in Escherichia coli. Further, a partial DNA sequence found the predicted NH2 terminus of alpha homologous with E. coli alpha. By plasmid integration and PBS1 transduction, we mapped alpha near rpsE and within the major ribosomal protein gene cluster on the B. subtilis chromosome. Additional DNA sequencing identified rpsM (encoding S13) and rpsK (encoding S11) upstream of alpha, followed by a 180 base-pair intercistronic region that may contain two alpha promoters. Although the organization of the alpha region resembles that of the alpha operon of E. coli, the putative promoters and absence of rpsD (encoding S4) immediately preceding the B. subtilis alpha gene suggest a different regulation. PMID- 3093468 TI - The comparative efficacy and safety of carbamazepine versus lithium: a randomized, double-blind 3-year trial in 83 patients. AB - The comparative usefulness of carbamazepine and lithium carbonate in the acute and prophylactic management of DSM-III diagnosed major affective, schizoaffective, or schizophreniform psychoses was investigated in a 3-year, prospective double-blind randomized trial with 83 in- and outpatients. The incidence of side effects was similar in both treatment groups, and side effects generally responded well to dosage reduction. Both drugs were effective in two thirds of the patients and appeared about equal in most outcome measures, except for a significantly higher dropout rate for patients with mood-incongruent psychotic features who were assigned to the lithium group. Both drugs appeared more effective in preventing excited rather than depressive symptoms. PMID- 3093469 TI - Medication-induced somnambulism in a patient with schizoaffective disorder. AB - A 39-year-old man with schizoaffective disorder experienced somnambulism only when taking a combination of lithium carbonate, chlorpromazine, triazolam, and benztropine. This was confirmed in the sleep laboratory. The sleepwalking occurred during Stage 2 sleep; the sleep record showed a marked paucity of REM sleep. The patient's brother had had one episode of somnambulism, also following exposure to a substance affecting the CNS. A role for CNS-active medications in triggering some pathologic sleep phenomena in predisposed individuals is hypothesized. Medications with central anticholinergic activity may be particularly important. PMID- 3093470 TI - The conformation of the lysyl side chain of substrates at the active center of trypsin. AB - In order to study the conformation of the side chain of lysine substrates bound to the active center of trypsin, two lysine analogs, cis- and trans-2,6-diamino-4 hexenoic acids (4,5-dehydrolysines) were synthesized and kinetic parameters for the hydrolysis of benzoyl methyl esters and phenylthiazolones of these analogs by this enzyme were compared with those of the corresponding lysine derivatives. The derivatives of cis-4,5-dehydrolysine were hydrolyzed much more slowly than those of lysine, owing largely to the small kcat values for the former. On the other hand, the derivatives of the trans-isomer were hydrolyzed at about the same rates as those of lysine and the values of both Km and kcat of the former are also similar to those of the latter. These results indicate that the conformation of the side chain of the lysine derivatives hydrolyzed by trypsin is such that the beta- and epsilon-carbons are in a trans-like conformation, as suggested by X-ray crystallographic studies of inhibitor-trypsin complex. PMID- 3093471 TI - Multiplicity of bovine liver GM1 ganglioside beta-galactosidase. AB - The multiplicity of bovine liver acid beta-galactosidase was investigated. Acid beta-galactosidase activity was measured in the presence of glucono-delta lactone, which inhibited the neutral beta-galactosidase activity but not the acid beta-galactosidase activity in bovine liver. Three forms of acid beta galactosidase were separated by Sephadex G-200 gel filtration and the elution pattern of the 4-methylumbelliferyl-beta-galactosidase activity coincided with that of the GM1-beta-galactosidase activity. These forms were relatively stable under acidic conditions (pH 4.5), but the two high molecular weight forms were inclined to dissociate into the low molecular weight form under neutral conditions (pH 7.0). The three forms of the enzyme showed similar pH-optima and apparent Michaelis constants for GM1 ganglioside. PMID- 3093472 TI - Separation and identification of two native forms of spinach ferredoxin by hydrophobic chromatography. AB - Hydrophobic chromatography on a TSK-gel Phenyl-5PW column separated highly purified spinach ferredoxin into two distinct molecular species in their native forms. The two ferredoxins showed almost the same absorption spectra in spite of a difference in amino acid composition. Both ferredoxins were active in the NADPH cytochrome c reducing system, and no significant difference was observed between their activities. The new separation method was also applied to ferredoxins highly purified from wheat plants and barley. Interestingly, all ferredoxin preparations so far examined contained two molecular species of ferredoxin. PMID- 3093473 TI - Isozymes of S-adenosylmethionine synthetase from rat liver: isolation and characterization. AB - S-Adenosylmethionine synthetase exists in at least two distinct forms, alpha- and beta-forms, in adult liver. The beta-form was purified to homogeneity from the soluble fraction of rat liver with a yield of about 10%. An antiserum directed against the purified beta-form from rat liver was prepared by injecting the purified enzyme into a rabbit. Ouchterlony double diffusion analysis and immunochemical titrations revealed that the isozymes, alpha- and beta-forms, are identical. Thus, the alpha-form was isolated from rat liver as a single protein using immunoaffinity chromatography against the beta-form. The molecular weights of the beta- and alpha-forms were determined to be 48,000 each by sodium dodecyl sulfate disc gel electrophoresis, and about 100,000, and 200,000, respectively, by Sephacryl S-200 gel filtration. These results indicate that the beta-form consisted of two subunits of 48,000 daltons and the alpha-form of four subunits of 48,000 daltons. The sedimentation coefficient was calculated to be 5.5S for the beta-form and 8.0S for the alpha-form. PMID- 3093474 TI - Xylosylation and glucuronosylation reactions in rat liver Golgi apparatus and endoplasmic reticulum. AB - We have studied in rat liver the subcellular sites and topography of xylosylation and galactosylation reactions occurring in the biosynthesis of the D-glucuronic acid-galactose-galactose-D-xylose linkage region of proteoglycans and of glucuronosylation reactions involved in both glycosaminoglycan biosynthesis and bile acid and bilirubin conjugation. The specific translocation rate of UDP xylose into sealed, "right-side-out" vesicles from the Golgi apparatus was 2-5 fold higher than into sealed right-side-out vesicles from the rough endoplasmic reticulum (RER). Using the above vesicle preparations, we only detected endogenous acceptors for xylosylation in the Golgi apparatus-rich fraction. The specific activity of xylosyltransferase (using silk fibroin as exogenous acceptor) was 50-100-fold higher in Golgi apparatus membranes than in those from the RER. Previous studies had shown that UDP-galactose is translocated solely into vesicles from the Golgi apparatus. In these studies, we found the specific activity of galactosyltransferase I to be 40-140-fold higher in membranes from the Golgi apparatus than in those from the RER. The specific translocation rate of UDP-D-glucuronic acid into vesicles from the Golgi apparatus was 10-fold higher than into those from the RER, whereas the specific activity of glucuronosyltransferase (using chondroitin nonasaccharide as exogenous acceptor) was 12-30-fold higher in Golgi apparatus membranes than in those from the RER. Together, the above results strongly suggest that, in rat liver, the biosynthesis of the above-described proteoglycan linkage region occurs in the Golgi apparatus. The specific activity of glucuronosyltransferase, using bile acids and bilirubin as exogenous acceptor, was 10-25-fold higher in RER membranes than those from the Golgi apparatus. This suggests that transport of UDP-D-glucuronic acid into the RER lumen is not required for such reactions. PMID- 3093475 TI - Isolation and characterization of a 1,4-beta-D-glucan glucohydrolase from the yeast, Torulopsis wickerhamii. AB - 1,4-beta-D-Glucan glucohydrolase (exo-1,4-beta-D-glucosidase) (EC 3.2.1.74) was isolated from growth supernatants of Torulopsis wickerhamii and was subjected to hydrodynamic, optical (CD), and kinetic analysis after purification to homogeneity by ammonium sulfate precipitation, size exclusion chromatography, ion exchange chromatography, and isopycnic banding centrifugation in cesium chloride. The last step was found to separate the enzyme from strongly associating, high molecular weight polysaccharide. Enzyme homogeneity was established by isoelectric focusing, sodium dodecyl sulfate-gel electrophoresis, and analytical high performance size exclusion chromatography using dual detection. The native exo-1,4-beta-D-glucosidase was found to be a dimer of 151,000 +/- 21,100 daltons by high performance size exclusion chromatography and 143,600 +/- 1,800 daltons by sedimentation equilibrium. The enzyme has a 12% linked carbohydrate content (mostly mannose) and no essential metal ions. Hydrolysis of p-nitrophenyl-beta-D glucopyranoside was found to be optimal at pH 4.25 and 50 degrees C. The enzyme was found to produce beta-D-glucose from cellodextrins (indicating retention of anomeric configuration during hydrolysis) and demonstrated depolymerization from the non-reducing polymer terminus. The enzyme followed competitive type inhibition with p-nitrophenyl-beta-D-glucopyranoside as substrate and demonstrated high values of Ki for D-glucose and D-cellobiose inhibition (190 and 230 mM, respectively). The exo-1,4-beta-D-glucosidase was found to hydrolyze cellotetraose more rapidly than D-cellobiose and aryl-beta-D-glycosides more rapidly than all other substrates. Low levels of activity were found for the polymeric substrates beta-glucan (yeast cell walls), Avicel, and Walseth cellulose. Although this enzyme demonstrates broad disaccharide substrate specificity, a characteristic common to beta-D-glucosidases from many sources, the ability to hydrolyze higher cellodextrins more rapidly than cellobiose renders this enzyme the first exo-1,4-beta-D-glucosidase purified from yeast. PMID- 3093476 TI - Inhibition of queuine uptake in diploid human fibroblasts by phorbol-12,13 didecanoate. Requirement for a factor derived from early passage cells. AB - Cell cultures derived from human neonatal foreskins (HF cells) are susceptible to phorbol-12,13-didecanoate- (PDD) induced inhibition of queuine uptake, but this inhibition is pronounced only in early passage HF cells. The present analysis of five different primary cultures demonstrated that, between 10 and 30 population doublings beyond the primary cultures, HF cells gradually became refractile to PDD-induced inhibition of queuine uptake, after which PDD begins to stimulate queuine uptake. Treating late passage HF cells with conditioned medium from early passage HF cells partially restored the PDD-induced inhibition of queuine uptake. This indicates the existence of a factor produced by early passage HF cells that permits PDD to inhibit queuine uptake. The tumor promoter, teleocidin, mimics the effects of PDD on queuine uptake. Both PDD and teleocidin are known to activate protein kinase C; therefore, this kinase may be an intermediary in tumor promoter induced effects on queuine uptake. Epidermal growth factor, platelet-derived growth factor, and transforming growth factor beta stimulated queuine uptake in both early and late passage HF cells. Growth factor stimulation of uptake was enhanced by PDD in late passage cells but inhibited by PDD in early passage cells. Polyinosinic polycytidylic acid treatment of late passage HF cells partially restored PDD-induced inhibition of queuine uptake. Human recombinant beta-interferon, plus or minus PDD, had no effect on queuine uptake. PDD did not inhibit queuine uptake in the immortal human and non-human cell lines examined. PMID- 3093477 TI - Binding of microtubule-associated protein 2 and tau to the intermediate filament reassembled from neurofilament 70-kDa subunit protein. Its regulation by calmodulin. AB - Two major brain microtubule-associated proteins (MAPs), MAP2 and tau, were found to bind to the intermediate filaments reassembled from neurofilament 70-kDa subunit protein (= 70-kDa filaments). The binding was saturable. The apparent dissociation constant (KD) for the binding of MAP2 to the 70-kDa filaments was estimated to be 4.8 X 10(-7) M, and the maximum binding reached 1 mol of MAP2/approximately 30 mol of 70-kDa protein. The apparent KD for the tau binding was 1.6 X 10(-6) M, and the maximum binding was 1 mol of tau/approximately 3 mol of 70-kDa protein. It was also found that MAP2 and tau did not compete with each other for binding to the 70-kDa filaments. Most interestingly, calmodulin, a ubiquitous Ca2+-binding protein in eukaryotic cells, was found to inhibit the binding of MAP2 and tau to the 70-kDa filaments. The inhibition by calmodulin was regulated by changes in Ca2+ concentration around 10(-6) M, and was canceled by trifluoperazine, a calmodulin inhibitor. PMID- 3093478 TI - Effects of sulfhydryl reagents and other inhibitors on Ca2+ transport and inositol trisphosphate-induced Ca2+ release from human platelet membranes. AB - The effects of modifiers of Ca2+ uptake and release in sarcoplasmic reticulum were studied in human platelet membranes. AgNO3,p-chloromercuribenzoate (pClHgBzO), N-ethylmaleimide (MalNEt), quercetin, vanadate, A23187, and caffeine all had the same effects on Ca2+ uptake in platelet membranes as had been observed for sarcoplasmic reticulum. These results strengthen our earlier conclusion that the Ca2+-pump proteins from internal human platelet membranes and muscle sarcoplasmic reticulum are very similar in functional properties. The sulfhydryl reagents Ag+ and pClHgBzO elicited rapid release of Ca2+ from platelet membranes in the presence of ATP, whereas MalNEt induced slow release. Quercetin also caused slow release of Ca2+ from platelet membranes in the presence of ATP. The effects of all three sulfhydryl reagents could be reversed by dithiothreitol, and Ag+-induced release was also reversed by ruthenium red. These effects are similar to those observed in sarcoplasmic reticulum, but in contrast caffeine did not induce Ca2+ release. In the absence of ATP, passively loaded platelet membranes did not release Ca2+ when exposed to sulfhydryl reagents. However, AgCl and pClHgBzO inhibited inositol trisphosphate (InsP3)-induced Ca2+ release from platelet membranes and this effect was reversed by dithiothreitol. Ruthenium red also inhibited InsP3-induced release, but ATP was found not to be required for InsP3-mediated release. LiCl enhanced Ca2+ release from platelet membranes. These results demonstrate that the InsP3-gated Ca2+ release channel is a separate entity from the Ca2+-pump and that essential protein sulfhydryls are involved in the release process. PMID- 3093479 TI - Induction of 32- and 34-kDa stress proteins by sodium arsenite, heavy metals, and thiol-reactive agents. AB - Challenge of human or murine melanoma cells with sodium arsenite, heavy metals (Zn2+, Cu2+ and Cd2+), or thiol-reactive agents (p-chloromercuribenzoate and iodoacetamide) induced the synthesis of four stress proteins with molecular masses of 100, 90, 72 (a doublet), and 32 (human) or 34 (murine) kDa. Enhanced expression of the 32- and 34-kDa polypeptides (p32 and p34) preceded or paralleled the synthesis of the other stress proteins. Hyperthermia, the calcium ionophore A23187, and amino acid analogs (L-azetidine-2-carboxylic acid and L canavanine) induced the formation of the major stress proteins, but failed to increase synthesis of p32 and p34. Characterization of the dose and time dependence of p32 and p34 synthesis in human (A375) and murine (B16-F10) melanoma cells, respectively, indicated that these proteins were subject to similar regulatory mechanisms. Electrophoretic analysis of stressed cells pulsed with different metabolic precursors revealed that p32 and p34 were radiolabeled with [35S]methionine or 3H-amino acids but not by [3H]mannose or [35S]cysteine. Polyclonal antibodies raised against human p32 cross-reacted with murine p34. These data suggest that p32 and p34 are closely regulated human and murine gene products, respectively, whose synthesis can be modulated by thiol-reactive reagents. Induction of p32 and p34 by these agents, but not by heat shock, suggests that these proteins are a subset of stress-inducible gene products. PMID- 3093480 TI - A cDNA encoding protein kinase C identifies two species of mRNA in brain and GH3 cells. AB - Antiserum raised against purified protein kinase C (the Ca2+/phospholipid dependent enzyme) (Ballester, R., and rosen, O. M. (1985) J. Biol. Chem. 260, 15194-15199) was used to screen a rat brain cDNA library in the prokaryotic expression vector lambda gt11. Three positive clones were isolated and shown to have overlapping restriction endonuclease maps. The positive recombinant phage with the longest cDNA insert (1.4 kilobases (kb)) was used for production of a beta-galactosidase fusion protein. Rabbit antiserum raised against the fusion protein recognized a single rat brain polypeptide of Mr 80,000 which was identified as protein kinase C by the following criteria: electrophoretic co migration with purified protein kinase C, partial co-purification with protein kinase C, and disappearance from the cytosol of phorbol 12-myristate 13-acetate treated GH3 cells. The nick-translated cDNA hybridized with two mRNAs, 8 kb and 3.5 kb, whose tissue distribution was in agreement with that reported for protein kinase C activity. Hybrid selection with immobilized cDNA identified mRNA encoding a protein of Mr 80,000 that could be precipitated by antibody to purified protein kinase C. Treatment of GH3 cells with phorbol 12-myristate 13 acetate, which promotes translocation and subsequent degradation of protein kinase C, did not alter the level of either message. PMID- 3093481 TI - Formation of dermatan sulfate by cultured human skin fibroblasts. Effects of sulfate concentration on proportions of dermatan/chondroitin. AB - [3H,35S]Dermatan/chondroitin sulfate glycosaminoglycans produced during culture of fibroblasts in medium containing varying concentrations of sulfate were tested for their susceptibility to chondroitin ABC lyase and chondroitin AC lyase. Chondroitin ABC lyase completely degraded [3H]hexosamine-labeled and [35S] sulfate-labeled dermatan/chondroitin sulfate to disaccharides. Chondroitin AC lyase treatment of the labeled glycosaminoglycans produced different results. With this enzyme, dermatan/chondroitin sulfate formed at high concentrations of sulfate yielded small glycosaminoglycans and larger oligosaccharides but almost no disaccharide. This indicated that the dermatan/chondroitin sulfate co-polymer contained mostly iduronic acid with only an occasional glucuronic acid. As the medium sulfate concentration was progressively lowered, there was a concomitant increase in the susceptibility to degradation by chondroitin AC lyase. Thus, the labeled glycosaminoglycans formed at the lowest concentration of sulfate yielded small oligosaccharides including substantial amounts of disaccharide. The smaller chondroitin AC lyase-resistant [3H,35S]dermatan/chondroitin sulfate oligosaccharides were analyzed by gel filtration. Results indicated that, in general, the iduronic acid-containing disaccharide residues present in the undersulfated [3H,35S]glycosaminoglycan were sulfated, whereas the glucuronic acid-containing disaccharide residues were non-sulfated. This work confirms earlier reports that there is a relationship between epimerization and sulfation. Moreover, it demonstrates that medium sulfate concentration is critical in determining the proportions of dermatan to chondroitin (iduronic/glucuronic acid) produced by cultured cells. PMID- 3093482 TI - Location of ligand-binding sites on the nicotinic acetylcholine receptor alpha subunit. AB - The portions of the Torpedo californica nicotinic acetylcholine receptor (AChR) alpha-subunit that contribute to the allosteric antagonist-binding site and to the agonist-binding site have been localized by affinity labeling and proteolytic mapping. [3H]Meproadifen mustard was employed as an affinity label for the allosteric antagonist-binding site and [3H]tubocurare as a photoaffinity label for the agonist-binding site. Both labels were found in a 20-kDa proteolytic fragment generated from the AChR alpha-subunit by Staphylococcus aureus V8 protease. This 20-kDa peptide also contains the 3H-labeled 4-(N-maleimido)-alpha benzyltrimethylammonium iodide-reactive site and binds 125I-alpha-bungarotoxin. N terminal sequencing established that the 20-kDa fragment began at Ser-173 of the alpha-subunit. Fluorescein isothiocyanate-conjugated concanavalin A could be bound to the second of the two major V8 cleavage products, an 18-kDa peptide. This peptide was also sensitive to treatment with endo-beta-N-acetyl glucosaminidase H, consistent with the presence of N-linked carbohydrate on this fragment. The N terminus of this peptide was found to be Val-46 of the alpha subunit sequence. Experiments designed to map disulfide bonds within the AChR alpha-subunit indicate that no bonds exist between the 18-kDa fragment (containing Cys-128 and Cys-142) and the 20-kDa fragment (containing Cys-192, Cys 193, and Cys-222). These results establish that the 20-kDa fragment contributes to both the acetylcholine and the allosteric antagonist-binding sites, whereas there is no evidence that the 18-kDa fragment is part of either site. PMID- 3093484 TI - Comparison in sensitized and unsensitized guinea-pigs of tuberculin PPDs RT 23 and PPD-M by skin tests and lymphocyte stimulation tests. Effect of immunization time. AB - The biological activities of tuberculin PPD RT 23 and the International Standard for Purified Protein Derivative of Mammalian Tuberculin (PPD-M) were compared in sensitized and unsensitized guinea-pigs by skin tests and lymphocyte stimulation (LS) tests. Estimates of relative potency (RP) from skin test results were dependent on the dose level, on the immunogen used, and, in guinea-pigs immunized with killed tubercle bacilli in oil, also on the immunization time. Relative potency estimates from LS results were dependent on the source of the lymphocytes and were different from estimates obtained from skin tests. Lymphocyte stimulation dose-response curves for the tuberculins were qualitatively different. In contrast to RT 23, PPD-M gave rise to non-specific skin reaction in unsensitized guinea-pigs. Both tuberculins were mitogenic to lymph node lymphocytes isolated from unsensitized guinea-pigs, PPD-M being the more mitogenic of the two tuberculins. The present results confirm that qualitatively different tuberculins cannot be unambiguously calibrated in identical terms and thus emphasize that the uncritical use of (international) standards should be avoided in tuberculin calibration. PMID- 3093483 TI - Analysis of pp60c-src protein kinase activity in human tumor cell lines and tissues. AB - We have evaluated the level of pp60c-src protein kinase activity in a variety of human tumor tissues and human tumor cell lines, and have estimated the abundance of the c-src protein in several of these tissues and cell lines. All cell lines derived from tumors of neuroectodermal origin that express a neural phenotype were found to possess c-src molecules with high levels of tyrosine-specific protein kinase activity. In contrast, cell lines derived from tumors of neuroectodermal origin that do not express neural characteristics, such as glioblastomas and melanomas, were found to have pp60c-src molecules with low levels of protein kinase activity. A similar pattern was observed when we analyzed the activity of c-src molecules extracted directly from corresponding tumor tissues. Analysis of human tumor cell lines derived from tissues other than those of neuroectodermal origin revealed that pp60c-src protein kinase activity was low in most cases. Exceptions to this observation were all rhabdomyosarcoma, osteogenic sarcoma, Ewing's sarcoma, and colon carcinoma lines tested. Comparison of pp60c-src kinase activity in normal skeletal muscle and rhabdomyosarcoma tissue and in normal breast tissue and breast adenocarcinoma tissue revealed that pp60c-src kinase activity was specifically elevated in the tumor tissues in both cases. However, the amount of pp60c-src protein in both normal and tumor tissues was found to be similar. These observations suggest that increases in the specific activity of the pp60c-src phosphotransferase in some rhabdomyosarcomas and breast carcinomas may be a characteristic acquired during the malignant transformation of the cells that is retained in cell lines established from these tumors. PMID- 3093485 TI - [Study of phages used in lysotyping of Listeria monocytogenes and proposal of classification by multidimensional treatment]. PMID- 3093486 TI - An evaluation of the polyacrylamide gel electrophoresis fractionation method for the production of Mycobacterium tuberculosis skin test preparations. I. Production, physiochemical characterization and serological analyses. AB - As a part of a cooperative inter-laboratory WHO supported project raw tuberculins were produced and purified protein derivative (PPD, 18.7 g protein) was prepared. Employing a multistage preparative polyacrylamide gel electrophoresis (PAGE) method the PPD was separated into four fractions corresponding to 15, 7, 4.75 and 3.5% gel concentrations. The PAGE procedure resulted in three lots of material- each representing 11 electrophoretic runs. Immunodiffusion analyses showed that the largest number of precipitinogens was found in the 15% fractions and that some precipitinogens cross-reacted with preparations of Mycobacterium bovis BCG, M. intracellulare, M. kansasii, M. smegmatis and M. vaccae. PMID- 3093488 TI - The development and standardization of an ELISA for ovalbumin determination in influenza vaccines. AB - A double antibody sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of ovalbumin in influenza vaccines has been developed and standardized. Commercially available reagents were used. ELISA was compared to single radial immunodiffusion (SRD) and immunoelectro-osmophoresis (IEOP) techniques. The detection limit by ELISA was 0.5 ng/ml. This method was found to be at least 1000 times more sensitive than SRD and at least 200 times more sensitive than IEOP. It was concluded that ELISA is a specific, sensitive and reproducible method for the determination of the small amounts of ovalbumin found as an impurity in unconcentrated influenza vaccines. PMID- 3093487 TI - An evaluation of the polyacrylamide gel electrophoresis fractionation method for the production of Mycobacterium tuberculosis skin test preparations. II. Comparative skin testing on guinea-pigs. AB - As part of a cooperative inter-laboratory WHO supported project for the fractionation of Mycobacterium tuberculosis skin test preparations, four fractions (designated 15, 7, 4.75 and 3.5%) were evaluated by comparative skin tests on sensitized guinea-pigs. The 7% fraction was the most potent in both homologously and heterologously sensitized animals, and the 4.75% and 3.5% gel fractions showed the lowest activity. Significant levels of cross-reactivity in guinea-pigs immunized with M. bovis BCG, M. kansasii, M. avium and M. intracellulare were demonstrated for all fractions examined, thus reflecting the antigenic relationships among these mycobacteria. These four fractions may qualify as starting material for further studies aiming at a reduction of skin test cross-reactivity. PMID- 3093489 TI - Studies on regional cerebral pH in patients with cerebral tumours using continuous inhalation of 11CO2 and positron emission tomography. AB - Regional cerebral pH (rpH) was measured in 12 patients with cerebral tumours and in 5 normal subjects using continuous inhalation of 11CO2 and positron emission tomography (PET). Cerebral tumours with a disrupted blood-brain barrier (BBB) on computed tomography scanning had a similar rpH to that of equivalent regions of contralateral brain tissue (mean tumour rpH, 6.98; mean contralateral brain pH, 6.99). Cerebral tumours with an intact BBB were consistently found to be more alkaline than contralateral brain tissue (mean tumour rpH, 7.09). There was no significant difference between the mean rpH values obtained for peripheral cortical gray and central white matter in normal subjects (7.02 and 6.98, respectively). It is concluded that in spite of reports of raised levels of aerobic glycolysis in neoplastic tissue, there is no evidence that cerebral tumour rpH values are depressed. PMID- 3093490 TI - 'Acute hepatitis' with fluctuating symptoms. PMID- 3093491 TI - Hoofbeats of a zebra in the emergency room. PMID- 3093492 TI - AIDS: what is now known. IV. Psychosocial aspects, treatment prospects. PMID- 3093493 TI - A test of clinical judgment. PMID- 3093494 TI - Hay on the vineyard: the American revolution in art. PMID- 3093495 TI - Cyanosis, stroke, and large P waves. PMID- 3093496 TI - Management of localized breast cancer. PMID- 3093497 TI - Mitochondrial genes and disease. PMID- 3093498 TI - Pain and its management. PMID- 3093499 TI - Psychotropic therapy: special concerns in the elderly. PMID- 3093500 TI - The Hunters: scientific genius, plain and fancy. PMID- 3093501 TI - A long view of treatment for mild hypertension. PMID- 3093502 TI - Evaluate the patient, not just the pain. PMID- 3093503 TI - Testing with horse serum: a warning. PMID- 3093504 TI - Tuberculin skin testing: when and how to use it. PMID- 3093505 TI - Recurrent seizures in a 'well-controlled' child. PMID- 3093506 TI - The significance of a prolonged Q-T interval. PMID- 3093507 TI - Geriatric skin problems. PMID- 3093509 TI - Organ transplants: the need for rational policies. PMID- 3093508 TI - A very cool and very distressed 12-year-old. PMID- 3093510 TI - Thyrotoxicosis after thyroidectomy. Iatrogenic or factitious? PMID- 3093511 TI - Obese young woman with exertional dyspnea. PMID- 3093512 TI - Thrombin purification by one-step preparative affinity chromatography on modified polystyrenes. AB - Insoluble polystyrenes substituted with sulphonate and L-arginyl methyl ester have been synthesized. Using their specific affinity for thrombin, we developed a simple one-step chromatographic procedure for thrombin purification. As a control, insoluble polystyrenes substituted only with sulphonate groups were tested. The results obtained confirmed the importance of the arginyl residues grafted onto these polymers to obtain an affinity matrix useful for purifying thrombin with a high specific activity and a good recovery. PMID- 3093513 TI - Improved high-performance liquid chromatographic method for the determination of 6-N,N,N-trimethyllysine in plasma and urine: biomedical application of chromatographic figures of merit and amine mobile phase modifiers. AB - An internally standardized method for the determination of 6-N,N,N trimethyllysine in human plasma, human urine, rat plasma, rat urine and hydrolyzed rat urine is described. This methylated amino acid and the procedural internal standard 6-N,N,N-trimethyllysine were isolated from the sample matrices using short ion-exchange columns and detected following high-performance liquid chromatography using a postcolumn reaction (o-phthalic-dicarboxaldehyde-2 mercaptoethanol) and fluorometric detection. The reliable detection limit for 6 N,N,N-trimethyllysine was 0.2 nmol/ml in 200 microliters of human plasma. The chromatographic separation exploits the unique properties of a novel tertiary amine mobile phase modifier, 3-(N,N-dimethylamino)-1,2-propanediol. The capacity factor and "Chromatographic Figures of Merit" (including peak asymmetry and relative system efficiency) were calculated for the chromatographic peak representing 6-N,N,N-trimethyllysine in over 2200 injections made while evaluating 900 biological specimens. PMID- 3093514 TI - Thin-layer chromatographic and column liquid chromatographic analyses of morphine in urine via dabsylation. AB - A semiquantitative screening method for morphine in urine and a quantitative assay method for the drug were developed. In the semiquantitative method, morphine in urine was directly reacted with 4-dimethylaminoazobenzene-4' sulphonyl chloride (dabsyl chloride) in a slightly alkaline medium. The orange coloured dabsyl morphine was separated by silica gel thin-layer chromatography and the spot intensity was visually compared with that of the standards. The limit of detection is 0.075 microgram/ml. In the quantitative method, morphine was extracted from urine before dabsylation. The dabsylation reaction is very fast and is complete within 5-10 min at room temperature. Dabsylation yield is maximum at a dabsyl chloride concentration of 6.2 mM. Total recovery of morphine using the extraction and dabsylation procedures described is 66%. Dabsyl morphine, thus formed, was analysed using high-performance liquid chromatography by monitoring its absorbance at 436 nm on a normal-phase mu Porasil column. The limit of quantitation using high-performance liquid chromatography is 0.26 microM (0.075 microgram/ml), which corresponds to 10.5 pmol of injected dabsyl morphine. Quantitative assay was also carried out by thin-layer chromatography on silica gel followed by densitometry. The limit of quantitation is 1.3 microM (0.375 microgram/ml). PMID- 3093515 TI - The collagen hydration hypothesis: a new paradigm for the secondary complications of diabetes mellitus. PMID- 3093517 TI - Acromegaly due to ectopic growth hormone (GH)-releasing hormone (GHRH) production: dynamic studies of GH and ectopic GHRH secretion. AB - Dynamic studies of GH and GH-releasing hormone (GHRH) secretion were performed in a man with a GHRH-producing carcinoid tumor and acromegaly. Insulin hypoglycemia stimulated and metoclopramide inhibited both GH and GHRH acutely. Bromocriptine suppressed GH both acutely and chronically without altering circulating GHRH levels and also blunted the GH response to exogenous GHRH. TRH acutely stimulated GH, but not GHRH, secretion, and iv bolus doses of synthetic GHRH-(1-40) stimulated GH release acutely. Somatostatin infusion decreased both GH and GHRH concentrations and blunted the GH responses to TRH and GHRH-(1-40). We conclude that prolonged exposure of the pituitary gland to high concentrations of GHRH is associated with chronic GH hypersecretion and may be accompanied by a preserved acute GH response to exogenous GHRH; a paradoxical response of GH to TRH may be mediated at the pituitary level, consequent to prolonged pituitary exposure to GHRH; bromocriptine suppression of GH in acromegaly is due to a direct pituitary effect of the drug; and somatostatin inhibits both ectopic GHRH secretion as well as GH responsiveness to GHRH in vivo. Since GH secretory responses in patients with somatotroph adenomas are similar to those in this patient, augmented GHRH secretion may play a role in development of the "classic" form of acromegaly. PMID- 3093516 TI - Apolipoproteins AI, AII and B in young adults: associations with CHD risk factors. The Beaver County experience. AB - Although the associations of lipoprotein lipids and apoproteins with coronary heart disease (CHD) risk factors have been examined in middle-aged populations, there is little data among younger subjects where these associations may be stronger. The authors quantitated apolipoproteins AI, AII and B as well as lipoprotein lipids in 172 young adults (aged 20-24 years) from a defined population in Beaver County, Penn. and examined cross-sectional associations with known risk factors. Female nonusers of oral contraceptives (OC) had higher mean concentrations of HDL-C and lower levels of LDL-C and triglycerides than men (p less than 0.05) although there was no significant sex difference in apo AI (p greater than 0.10), while apo B was higher among men (p less than 0.01). OC use was positively related to apo AI and AII (p less than 0.05) but not to HDL-C. Cigarette smoking was inversely associated with apo AI, AII and HDL-C while alcohol intake was positively associated with these factors. These results suggest that in general, correlates of lipoprotein lipids and apoproteins in young adults parallel those in middle-aged subjects and suggest further that quantitation of both at an early age may help prevent CHD and further elucidate the atherosclerotic process. PMID- 3093518 TI - Pharmacokinetic characteristics of the gonadotropin-releasing hormone analog D Ser(TBU)-6EA-10luteinizing hormone-releasing hormone (buserelin) after subcutaneous and intranasal administration in children with central precocious puberty. AB - A double antibody RIA was developed for the measurement of the long-acting GnRH agonist D-Ser(TBU)6EA10GnRH (buserelin). The antibody, raised in rabbits against a buserelin-hemocyanin conjugate, reacted with the intact molecule and also molecular fragments containing the C6-9 tetrapeptide sequence and permitted the measurement of buserelin activity in serum and urine. Natural GnRH, LH, and FSH did not cross-react in this assay system. The assay was applied to samples obtained from children receiving buserelin for the management of central precocious puberty either by once daily injection of 30 micrograms/kg or by nasal spray (in; 200 micrograms every 8 h). Urine and serum samples, chromatographed on Sephadex G-25, contained immunoreactive material corresponding closely in molecular size to [125I]buserelin. In unextracted serum samples taken at intervals after sc therapy in 11 girls, the peak immunoreactive buserelin levels of 52.2 +/- 14.8 ng/ml (mean +/- SEM) occurred at 30 min. The half-time of elimination was 74.9 +/- 36.9 min. Approximately 30% of the dose was detected in urine collected for 3 h after injection. Similar data were obtained in 3 normal adults given 10 micrograms/kg buserelin, iv. By contrast, after the administration of 200 micrograms buserelin by metered nasal spray, the mean peak serum concentration in 10 girls was 100-fold less (0.65 +/- 0.14 ng/ml), although the halftime of elimination was almost identical. Only 0.73% of the nasal dose was excreted by 3 h. Calculated relative bioavailability data indicated maximal nasal absorption of 6%. However, absorption after nasal administration varied greatly, and in 2 children, serum and urinary concentrations of buserelin after supervised administration were negligible. We conclude that in buserelin therapy, in the dose used in this study, does not represent optimal treatment for the initial management of patients with precocious puberty. The success of in therapy in sustaining initial effects of buserelin given by sc administration presumably reflects changes in receptor sensitivity induced by sc treatment. PMID- 3093519 TI - Effect of overnight constant infusion of human growth hormone (GH)-releasing hormone-(1-44) on 24-hour GH secretion in children with partial GH deficiency. AB - A continuous infusion (0.5 or 1 microgram/kg X h) of GH-releasing factor-(1-44) [GHRH-(1-44)] was administered from 2000-0800 h to 16 children with GH deficiency, defined as a maximum peak plasma GH less than 11 ng/ml in response to 2 provocative tests [first test; mean, 7.4 +/- 2.6 (+/- SD) ng/ml; second test; mean, 8.4 +/- 2.4 ng/ml]. Eight were boys and 8 girls; their average age was 10 yr, 5 months; and growth was retarded in all [mean, -3 +/- 0.6 (+/- SD)]. Polygraphic monitoring was carried out during the night, and blood samples for plasma GH measurements were drawn every 20 min during the night and the following day. A control study had been carried out in the preceding months with the same children. During GHRH infusion, a significant increase in nocturnal GH secretion occurred; the mean maximum peak increased from 17.5 +/- 3.4 (+/- SD) to 38.7 +/- 3.2 ng/ml, the mean area under the curve from 2243 +/- 459 to 5348 +/- 710 ng/ml, the mean integrated concentration from 4.2 +/- 0.8 to 9.9 +/- 1.3 ng/ml X min, and the mean number of peaks above 5 ng/ml from 2.7 +/- 0.3 to 4.7 +/- 0.4. During GHRH infusion, the 16 children had 2 peaks during the first 4 h of sleep and a third peak at the end of the night. Plasma GH levels the day after the infusions were not significantly increased. We conclude that continuous nocturnal GHRH infusion increases pulsatile sleep GH secretion throughout the night in children with partial GH deficiency. PMID- 3093520 TI - Total estradiol, free estradiol, sex hormone-binding globulin, and the fraction of estradiol bound to sex hormone-binding globulin in human follicular fluid. AB - Sex hormone-binding globulin (SHBG), percent free estradiol (E2), the fraction of E2 bound to SHBG, and total E2 were measured in the serum and follicular fluid of 12 women (25 follicles) who had received gonadotropin stimulation in an in vitro fertilization program. The women were classified as high or low responders based on peak serum E2 levels (high responders: peak E2, greater than 1500 pg/ml; low responders: peak E2, less than 1000 pg/ml). During treatment, serum levels of SHBG increased in high responders from 55 +/- 8.8 (+/- SEM) to 96 +/- 16 nM (P less than 0.01), but did not change in low responders. SHBG was more concentrated in follicular fluids from high responders (142 +/- 12.5 nM) than in those from low responders (44.4 +/- 5.8 nM). A positive correlation was found between serum and follicular fluid levels of SHBG (r = 0.873; P less than 0.01). In follicular fluid, total E2 levels, which varied from 100-2650 ng/ml, correlated (r = 0.790; P less than 0.01) closely with SHBG levels. The percent free E2 averaged 5.9% (range, 4-10.6%) in follicular fluid compared to 1.8% (range, 1.5-2.1%) in serum. An inverse correlation (r = -0.661; P less than 0.01) was found between total E2 concentrations and percent free E2 in follicular fluid. The relationship between serum and follicular fluid levels of SHBG suggests that SHBG in follicles arises from the circulation. Although SHBG is present in follicular fluid in amounts similar to those in serum, the large quantities of E2 in preovulatory follicules exceed the binding capacity for SHBG, and the majority of E2 appears to be bound to albumin. Hence, it seems unlikely that SHBG in follicular fluid regulates estrogen action in ovarian target cells. PMID- 3093521 TI - Ketoconazole-induced stimulation of gonadotropin output in men: basis for a potential test of gonadotropin reserve. AB - The antifungal drug ketoconazole is known to inhibit testosterone biosynthesis and decrease serum testosterone concentrations. To assess whether the ketoconazole-induced reduction in serum testosterone might stimulate LH and FSH output in a manner suitable as a test of pituitary gonadotropin reserve, we gave normal men ketoconazole every 8 h for 1 week in dosages of 300-1200 mg/day. Ketoconazole administration caused a dose-dependent reduction in serum testosterone which correlated inversely with serum ketoconazole (r = -0.82; P less than 0.001). This fall in serum testosterone stimulated increases in serum LH and FSH which were maximal at a ketoconazole dose of 900 mg/day [LH increase, 127 +/- 27% (+/- SEM); FSH increase, 63 +/- 15%]. Ketoconazole tended to blunt the LH and FSH responses to LHRH. Ketoconazole increased serum 17 hydroxyprogesterone, reflecting blockade of 17,20-desmolase by the drug, while having inconsistent effects on serum estradiol. I conclude that ketoconazole administration for 1 week to normal men stimulates LH and FSH output in a fashion that makes it potentially suitable, after additional verification in subjects with normal and abnormal pituitary-testicular function, as a test of pituitary gonadotropin reserve. PMID- 3093522 TI - Inherited heat-stable variant thyroxine-binding globulin (TBG-Chicago). AB - The five known types of inherited variant T4-binding globulin (TBG) have in common increased sensitivity to heat denaturation compared to the common type TBG (TBG-C). In the course of studies to screen for and characterize variant TBGs in population groups, we detected a unique TBG with marked resistance to heat denaturation. The propositus was a 22-year-old black man without personal or family history of thyroid disease. His native TBG (nTBG) in serum had a t1/2 of denaturation at 56 C of 90 min compared to a mean value of 6.8 +/- 1.1 (+/- SD) min for TBG-C. This variant TBG, termed TBG-Chicago, was also resistant to acid denaturation, but was indistinguishable from TBG-C in terms of immunoreactivity, microheterogeneity on isoelectric focusing, and affinity for T4. It had a single T4-binding site and a normal concentration in serum associated with iodothyronine levels within the normal range. The mode of inheritance of TBG-Chicago appears to be X-chromosome linked. The mother of the propositus was heterozygous; her serum contained approximately 40% TBG-Chicago and 60% of another variant TBG common in blacks, TBG-S. The father had TBG-C, a trait that was not transmitted to his son. The exact nature of this variant TBG is not known. It most likely represents a mutation in the polypeptide chain of the molecule with formation of stronger intramolecular bonds. PMID- 3093523 TI - Androgen insensitivity in oligospermic men: a reappraisal. AB - Androgen insensitivity has been reported to be present in as many as 40% of patients with severe oligospermia. In order to evaluate further the role of androgen resistance in male infertility we studied 24 men with severe oligospermia. Plasma T and LH were measured by RIA and the T X LH product was calculated. Fibroblasts were grown from genital skin obtained during testicular biopsies and androgen receptor maximal binding capacity (BMAX) and affinity (KD) were measured in fibroblast monolayers. Pubic skin 5 alpha-reductase activity, an androgen-dependent enzyme, was measured in skin homogenates. Plasma T values were in the upper normal range [7.0 +/- 1.7 (SEM) ng ml-1] whereas the T X LH product was high (greater than 50) in only six patients. Mean BMAX and KD values for the androgen receptor were normal [BMAX: 788 +/- 259 fmol mg DNA-1 (patients, n = 20), 726 +/- 227 (normal men, n = 20), and KD: 0.27 +/- 0.24 (patients, n = 20), 0.18 +/- 0.09 (normal men, n = 15), respectively]. However, four men had supranormal KD values. The mean BMAX was also normal when the group of men with sperm densities below 10(6) per ejaculate was considered separately. Public skin 5 alpha-reductase activity was normal in all but four patients (patients: 177.1 +/- 91 fmol/mg skin/h, n = 30, normal men: 210 +/- 45, n = 20 patients). In conclusion, androgen receptor BMAX levels were normal in all patients studied, regardless of the sperm density and the T X LH product. Pubic skin 5 alpha reductase activity was also normal in all but four patients. In these four patients, a qualitative defect of the androgen receptor cannot be excluded. In this group of patients with severe oligospermia, infertility did not seem to be related to quantitative abnormality of the androgen receptor as was previously reported. PMID- 3093525 TI - Pig skin as test substrate for evaluating topical antimicrobial activity. AB - The feasibility of using pathogen-contaminated pig skin as a model substrate for evaluating skin disinfectants was demonstrated. A test methodology is described that is safe, convenient to use, and adaptable to a variety of hand-washing conditions. The treatment protocol, pathogen contamination conditions, and application technique variables can all be carefully controlled to simulate clinical use conditions. The number of organisms transferred by contact was compared with the total organism count on the pig skin. The quantity of organisms transferred ranged from 10 to 60% of the total organisms, depending on the nature of the contamination conditions. The cumulative results of multiple imprint and stripping measurements were consistent with the concentration of inoculated organisms. Tests with alcohol solutions validated the methodology and clearly showed the dependence of topical antimicrobial activity on both the concentration and structure of the alcohol. Activity increased with increasing alcohol concentration and in the following order: ethanol, isopropanol, and n-propanol. All of the alcohols became less active as the severity of the test conditions was increased, i.e., higher inoculum levels for a longer incubation time before treatment. The contact imprint and stripping methods used to evaluate bacterial growth on the skin clearly showed that the alcohol treatments reduced but did not eliminate the inoculated pathogens. It was found that long lifetimes (several hours) for pathogens on the skin are possible under some environmental conditions. This observation strongly suggests that frequent hand washing is a necessary infection control practice even when opportunities for repeated pathogen contamination have not occurred. PMID- 3093524 TI - Variation and adaptation of Pseudomonas aeruginosa toxicity to HeLa cells and fibroblasts. AB - The toxic components of supernatants from Pseudomonas aeruginosa cultures directed against HeLa cells and Staphylococcus aureus were evaluated with the aim of discovering interactions. Supernatants of eight different strains of P. aeruginosa were assayed for cytotoxic activity. All were active against HeLa cells; seven were toxic for S. aureus. On repeated suspension of P. aeruginosa in 0.9% sodium chloride solution, a shift from HeLa cell toxicity to staphylococcal lytic activity occurred along with a change of toxic activity from a high (50,000 +/- 5,000) to a low (8,000 +/- 400) molecular weight (MW) range on gel filtration. Addition of protein to the minimal medium of cultures producing material toxic only for S. aureus reactivated the generation of HeLa cell-toxic material. Cultivation of P. aeruginosa in the presence of HeLa cells and a chloramphenicol supplement produced suppression of the generation of material toxic for S. aureus but facilitated that of HeLa-toxic material of high MW. Adaptation of toxicity against fibroblasts developed only on cocultivation of P. aeruginosa together with S. aureus and in the presence of fibroblasts. Under these conditions a strong lytic activity for S. aureus appeared, even in the presence of chloramphenicol. Chloramphenicol caused the material toxic for fibroblasts to elute at a low MW well separated from that toxic for HeLa cells. In contrast to the high-MW toxic substances, the low-MW material did not induce antibodies after injection into rabbits. This may explain failures of vaccination against P. aeruginosa infection and of serum therapy of homologous sepsis in humans. PMID- 3093526 TI - Antibiograms, serotypes, and plasmid profiles of Pseudomonas aeruginosa associated with corneal ulcers and contact lens wear. AB - Pseudomonas aeruginosa was isolated from the corneal scrapings of 11 of 14 patients with gram-negative corneal ulcers and from salt tablet-prepared saline solutions from 6 of these patients wearing soft contact lenses. Comparison of physiological properties, antibiograms, serotypes, and plasmid profiles for five of the patients indicated that the isolates from the ulcer and the saline solution of a given patients were of the same strain. Improper hygienic practices of contact lens wearers appeared to be a major factor in the epidemiology of pseudomonad corneal ulcers. PMID- 3093527 TI - Evaluation of blood clot cultures for isolation of Salmonella typhi, Salmonella paratyphi-A, and Brucella melitensis. AB - Two types of clot culture, one with taurocholate-streptokinase and the other with bile as a culture medium, and two conventional cultures of whole blood were evaluated in parallel in an area where typhoid fever and brucellosis are endemic. Each of the four systems contained 5 ml of blood or the clot derived from 5 ml of blood and sufficient broth to yield a 1:11 dilution of the specimen. Of 542 patients studied, Salmonella paratyphi-A was isolated from 61, S. typhi from 46, and Brucella melitensis from 30. The two clot cultures yielded the salmonellae equally well; both were superior to whole blood cultured in Trypticase soy broth (P less than 0.02) but not to whole blood cultured in bile (P greater than 0.05). Only two systems were successful for isolation of B. melitensis. Blood-Trypticase soy broth identified 28 (93%), and clot-streptokinase cultures identified 21 (70%) (P greater than 0.05). The data indicate that use of clots per se offers no advantage in sensitivity over procedures which use whole blood. Nonetheless, they are excellent for isolation of enteric fever salmonellae and can be performed with clots left over after serum is removed for serological, biochemical, or other tests. PMID- 3093528 TI - Do clinical microbiology laboratories report complete bacteriology in urine from patients with long-term urinary catheters? AB - Bacteriuria associated with long-term urinary catheters (those in place for greater than or equal to 30 days) appears to be the most common nosocomial infection in U.S. medical care facilities. This bacteriuria is polymicrobial and dynamic and accompanied by fevers, catheter obstructions, bacteremias, and deaths. We compared the reporting by our research laboratory of bacteria present in urine from long-term-catheterized nursing home patients with that by two commercial laboratories. The commercial laboratories isolated significantly fewer bacterial species at 10(5) CFU/ml of urine specimen. Organisms well recognized as causes of urinary tract infections in noncatheterized patients (Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae) were isolated in comparable frequencies by both the research and commercial laboratories. However, other organisms, including uncommon uropathogens like Providencia stuartii and Morganella morganii, which were actually among the most frequent bacteriuric species in these long-term-catheterized patients, were isolated significantly less frequently by the commercial laboratories. Reasons for the discrepancies are unclear but may involve use of different techniques. More complete reporting may lead to better understanding of the polymicrobial bacteriuria of long-term catheters and its associated complications. This, in turn, may result in improved patient care and infection control in nursing homes. PMID- 3093529 TI - Modification of the Sceptor system for rapid detection of methicillin-resistant staphylococci. AB - The 24-h Sceptor MIC system (Johnston Laboratories, Inc., Towson, Md.) was modified to allow rapid (6 h) detection of methicillin-resistant staphylococci. For 105 methicillin-resistant staphylococci tested, 90% of the results obtained by the 6-h method agreed with those obtained by disk agar diffusion. In comparison, 88 and 93% of the results obtained by the AutoMicrobic system (Vitek Systems, Inc., Hazelwood, Mo.) and the 24-h conventional Sceptor system, respectively, agreed with disk agar diffusion results. No false-resistant results were observed with 52 methicillin-susceptible staphylococci tested by any of the three methods. PMID- 3093530 TI - Determination of interferon-gamma in the peripheral blood of multiple sclerosis patients in remission, using a chemiluminescence technique. AB - The plasma from eight patients with multiple sclerosis (MS) whose disease was in remission, was investigated by a chemiluminescence technique for its ability to stimulate the oxidative metabolism of peripheral blood monocytes (PBM). The active fraction identified had a molecular weight between 13,700 and 43,000 Da. Its activity was reduced by incubation at pH 2, pH 4 or pH 6, or by treatment at 56 degrees C for 1-3 h. The activity was also decreased, 58-100%, by prior incubation with antibodies to human interferon-gamma (IFN-gamma). We suggest that these results indicate that the increased chemiluminescence activity (CL-A) of PBM in MS patients in remission is due mainly to the presence of circulating IFN gamma. PMID- 3093531 TI - Ontogenesis of thyrotropin-releasing hormone in the human fetal pancreas. A combined radioimmunological and immunocytochemical study. AB - The ontogenesis of pancreatic thyrotropin-releasing hormone (TRH) in the human fetal gland was studied by radioimmunoassay or immunocytochemistry. The highest TRH concentrations (1,508.5 +/- 382.3 pg/mg wet wt) were detected between 6 and 8 wk of gestation. From 9 to 12 wk, TRH declined to 365.2 +/- 127.4 pg/mg wet wt and remained low thereafter (96.1 +/- 28.9 pg/mg wet wt). The immunocytochemical procedure was performed on semithin and thin sections from 12- to 19-wk-old human fetuses. At the light microscope level, TRH was found interspersed among the islet cell clusters (12 wk), and later (16 wk) inside the typical islets of Langerhans. Consecutive semithin sections treated by TRH and insulin antisera showed the same immunoreactive cells. Electron microscopy showed TRH in B cell secretory granules. These results are consistent with an eventual implication of TRH in the endocrine regulation of metabolism or in the fetal development of pancreas. PMID- 3093532 TI - Antibodies to neurofilament protein in retinitis pigmentosa. AB - Antibodies reactive with heterologous neural tissue were detected by indirect immunofluorescence microscopy in the sera of 17 of 34 patients with retinitis pigmentosa, one of 30 normal control sera, and a variable percentage of sera derived from subjects with diverse ocular and neurological diseases. These antibodies were also found both in disease-free first degree relatives and in spouses of patients with retinitis pigmentosa. Analytical sodium dodecyl sulfate polyacrylamide gel electrophoresis of human spinal cord components followed by immunoblots with sera under study revealed that the serum antibody was specific for the high molecular weight protein subunit of neurofilaments. No correlation was found between the presence of these antibodies and other immunological and clinical parameters in retinitis pigmentosa. These findings suggest that release of piled-up neurofilaments from damaged neurones in retinitis pigmentosa triggers B lymphocytes autoreactive to neurofilament antigens. PMID- 3093533 TI - Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus. AB - The effect of plasma on degradation of human growth hormone-releasing hormone (GRH) was examined in vitro and in vivo using high performance liquid chromatography (HPLC), radioimmunoassay (RIA), and bioassay. When GRH(1-44)-NH2 was incubated with human plasma, the t1/2 of total GRH immunoreactivity was 63 min (RIA). However, HPLC revealed a more rapid disappearance (t1/2, 17 min) of GRH(1-44)-NH2 that was associated with the appearance of a less hydrophobic but relatively stable peptide that was fully immunoreactive. Sequence analysis indicated its structure to be GRH(3-44)-NH2. Identity was also confirmed by co elution of purified and synthetic peptides on HPLC. Biologic activity of GRH(3 44)-NH2 was less than 10(-3) that of GRH(1-44)-NH2. After intravenous injection of GRH(1-44)-NH2 in normal subjects, a plasma immunoreactive peak with HPLC retention comparable to GRH(3-44)-NH2 was detected within 1 min and the t1/2 of GRH(1-44)-NH2 (HPLC) was 6.8 min. The results provide evidence for GRH inactivation by a plasma dipeptidylaminopeptidase that could limit its effect on the pituitary. PMID- 3093534 TI - In vitro myotrophic effect of serum kappa chain immunoglobulins from a patient with kappa light chain myeloma and muscular hypertrophy. AB - Muscle hypertrophy due to enlarged muscle fibers was accompanied by kappa light chain myeloma in a 62-yr-old man. Immunofluorescence showed kappa light chain deposits around muscle fibers. We hypothesized that a circulating growth factor may be involved in the pathogeny of this muscular hypertrophy. Patient serum cultured with muscle cells showed that (a) the patient's serum exhibited a trophic effect on human muscle cells in culture, (b) this trophic effect increased the differentiation and did not influence the proliferation of human muscle cells, and (c) the fraction of the patient's serum immunoadsorbed on antihuman kappa chain antibodies exhibited the same in vitro effect on the muscle cells, whereas the fraction immunoadsorbed on antihuman lambda chain antibodies did not. These results support the hypothesis that the patient's kappa light chains have a specific enhancing effect on human muscle cell differentiation, perhaps leading to an acquired muscular hypertrophy. PMID- 3093536 TI - Vitamin stability in a TPN mixture stored in an EVA plastic bag. AB - In order to examine the stability of vitamins in a TPN admixture stored in 3 litre plastic (EVA) bags, two different stability studies were performed. In the first experiment the TPN admixture was stored in darkness at 2-8 degrees C for 96 h and the stability of vitamins determined. The vitamins examined were retinyl palmitate, alpha-tocopherol, thiamine mononitrate, sodium ascorbate (analysed as reduced ascorbic acid and dehydroascorbic acid), sodium riboflavin-5'-phosphate, pyridoxine hydrochloride, nicotinamide, folic acid, biotin, sodium pantothenate and cyanocobalamin. In the second test the stability of vitamins was determined during simulated infusion from the bag containing the admixture. The vitamins examined were retinyl palmitate, alpha-tocopherol, sodium riboflavin-5'-phosphate and sodium ascorbate (analysed as reduced ascorbic acid and dehydroascorbic acid). The vitamin stability was found to be acceptable for all vitamins except ascorbic acid and folic acid. Total ascorbic acid is the sum of reduced ascorbic acid and dehydroascorbic acid (DHA). It is important to estimate the total ascorbic acid concentration because DHA is also biological active. About 50% of the nominal total ascorbic acid remained after 96 h of storage at 2-8 degrees C in darkness, or after 24 h of simulated infusion initiated immediately after mixing. With folic acid there appears to be assay interference which requires further investigation. PMID- 3093535 TI - Immune responses during human Schistosomiasis mansoni. Evidence for antiidiotypic T lymphocyte responsiveness. AB - We present a method for the examination of antiidiotypic cell-mediated reactivity during chronic human infections. Pooled and individual sera from patients with schistosomiasis mansoni were purified on immunoaffinity columns of schistosomal egg antigens (SEA). The eluates contained anti-SEA antibodies, but not SEA. These antibody preparations, and their F(ab)2 fragments, stimulated dose-dependent proliferation of peripheral blood mononuclear cells (PBMN) and T lymphocytes from some, but not all active or former schistosomiasis mansoni patients, and could do so autologously. Stimulation required presentation by plastic-adherent cells. The eluates did not stimulate PBMN from persons who had never had schistosomiasis. Affinity-purified anti-SEA antibodies from former patients (cured for greater than 10 yr) did not stimulate PBMN from patients with active infections. Reabsorption on SEA columns removed stimulatory activity from the eluates. We propose that multiclonal, SEA-related idiotypes expressed by some anti-SEA antibodies stimulate proliferation of T lymphocytes that express antiidiotypic specificities. PMID- 3093537 TI - Asymptomatic carriage of Clostridium difficile in patients with cystic fibrosis. AB - Faecal samples from 37 patients with cystic fibrosis and 40 control patients at the Brompton Hospital and the London Chest Hospital were examined for the presence of Clostridium difficile. The organism was isolated from 2 (17%) of control patients who were receiving antibiotics and from one (3.6%) of control patients who had no antimicrobial treatment. Thirty two per cent of the patients with cystic fibrosis excreted C difficile, though none of them had diarrhoea. Two of the three isolates from control patients and nine of the 12 isolates from patients with cystic fibrosis produced toxin B (cytotoxin) in vitro. Toxin B was present in the stools of one of the control patients and three of the patients with cystic fibrosis; toxin A (enterotoxin) was not detected in the faeces of the patients with cystic fibrosis. Two cytotoxigenic strains of C difficile isolated from patients with cystic fibrosis were examined in hamsters; both were virulent, and the animals died. PMID- 3093538 TI - Determination of Rh(D) genotype: use of human monoclonal antibodies in flow cytometry. PMID- 3093539 TI - Effect of in vitro sodium citrate anticoagulant on results of arterial blood gas analysis. PMID- 3093540 TI - New marker for mesothelioma: an immunoperoxidase study. AB - An antibody was raised against a protein isolated from the cytoplasm of mesothelioma cells. It was subsequently used in an immunoperoxidase procedure on formalin fixed, paraffin embedded tissue sections. A representative sample of benign and malignant tumours from all the systems of the human body was examined. All the tumours derived from coelomic surfaces (mesotheliomas of pleura, peritoneum, and ovary, and adenomatoid tumour of epididymis) reacted with the antibody. No other tumour tested in this study expressed the protein. These findings indicate that the antibody may be useful in the identification of mesothelioma cells in both histological and cytological diagnostic routine practice when morphological interpretation is in doubt. PMID- 3093541 TI - Synaptic reorganization in the motor trigeminal nucleus of the rat following neonatal 6-hydroxydopamine treatment. AB - The synaptic organization of the motor trigeminal nucleus in adult rats treated neonatally with 6-hydroxydopamine (6-OHDA) was investigated quantitatively and compared with control nuclei. No statistically significant change was detected in the distribution of axon terminals in the neuropil, and the total number of axosomatic contacts per unit length of membrane was identical in the control and 6-OHDA-treated groups. However, 6-OHDA treatment causes a significant redistribution of the four morphologically distinct bouton populations forming axosomatic contacts with trigeminal motoneurons. Terminals containing lucent axoplasm and spherical synaptic vesicles have been identified as norepinephrine neuron terminals (Card et al.: J. Comp. Neurol. 250:469-484, '86). These and terminals with lucent axoplasm and pleomorphic vesicles are increased in number whereas terminals with dense axoplasm and either spherical or pleomorphic synaptic vesicles are decreased in number in the 6-OHDA-treated brains compared to controls. These results confirm that the norepinephrine hyperinnervation observed in histofluorescence preparations following neonatal 6-OHDA treatment reflects an increase in absolute numbers of norepinephrine terminals. The finding that the total number of axosomatic contacts per unit length of membrane remains constant while the proportions of individual afferent classes vary may indicate that the trigeminal motoneuron plays a major role in determining the overall density but not necessarily the individual specificity of its axosomatic innervation. The motor trigeminal nucleus is a useful model system in which to investigate both the response of norepinephrine fibers to neonatal 6-OHDA treatment and the respective roles of a target neuron and its afferents in the regulation of appropriate quantitative innervation patterns in the central nervous system. PMID- 3093542 TI - Adenocarcinoma of the large bowel and colitis in captive cotton-top tamarins Saguinus o. oedipus. AB - The gross and microscopic appearance of large bowel adenocarcinoma in two young adult, captive-born cotton-top tamarins is described. A retrospective examination of sections of colons from other animals that had died in the colony revealed a high incidence of chronic colitis. The adenocarcinomas, which resembled those reported from colonies of this species in the U.S.A., are thought to be the first seen in Great Britain. PMID- 3093543 TI - The effect of in vivo modulation of macrophage activities on Mycobacterium lepraemurium infection. AB - During the early stage of Mycobacterium lepraemurium (MLM) infection in mice, the mononuclear phagocyte system (MPS) was activated non-specifically as demonstrated by enhanced listericidal activity. Such listericidal activity could be further increased by Corynebacterium parvum treatment, indicating that MLM was not a good MPS stimulant. Corynebacterium parvum treatment conferred only marginal protection upon mice during MLM infection, as shown by the slight but significant prolongation of survival time and decreased bacillary load. In contrast, mice could not control splenic Listeria growth in the later stage of infection regardless of C. parvum treatment. Adoptive transfer of Listeria-immune spleen lymphocytes, however, did significantly suppress splenic Listeria growth. The significance of these findings is discussed. PMID- 3093544 TI - Treating erythema chronicum migrans of Lyme disease. AB - The efficacy of antibiotic treatment of 117 patients with erythema chronicum migrans of Lyme disease was evaluated in terms of the necessity for retreatment and the prevention of the late manifestations of Lyme disease. Fifty-six patients with a minor form of the illness did not require retreatment and did not develop late manifestations following antibiotic treatment. Three pregnant patients were included in this group. Fourteen of sixty-one patients with a major form of the illness required retreatment, and five developed posttreatment late manifestations of Lyme disease consisting of Bell's palsy and persistent joint pain. Although the preferred antibiotic for treating erythema chronicum migrans of Lyme disease has not been conclusively established, tetracycline and penicillin proved effective. The use of probenecid plus penicillin may be of benefit to patients with the major form of the illness. PMID- 3093545 TI - Sensitivity and specificity of IgA-class antiendomysial antibodies for dermatitis herpetiformis and findings relevant to their pathogenic significance. AB - The specificity and sensitivity of the recently reported IgA-class antiendomysial antibody test for gluten-sensitive enteropathy were evaluated in four double blind studies involving the sera of fifty-seven patients with dermatitis herpetiformis who were not on a gluten-free diet and ninety-seven assorted control sera. The control sera provided by the four centers included the sera of nineteen patients with dermatitis herpetiformis and two with celiac disease who were on a gluten-free diet, the sera of five normal subjects with human lymphocyte antigens (B8 locus), the sera of thirteen patients with linear IgA bullous dermatosis, and fifty-eight other control sera, mostly from patients with other bullous diseases and other dermatoses. The frequency of IgA antiendomysial antibody in these coded studies was zero of ninety-seven control sera and thirty four of fifty-seven sera (60%) from patients with dermatitis herpetiformis who were not on a gluten-free diet. The pathogenic role of IgA antiendomysial antibodies in dermatitis herpetiformis and celiac disease is suggested not only by their high degree of disease sensitivity and specificity but also by their formation in response to gluten challenge, their appearance before gut changes, and the in vitro binding of gliadin to the antiendomysial antibody antigen sites. These and other findings in this study and in the literature suggest that gluten sensitive enteropathy is immunologically mediated and that IgA antiendomysial antibodies play a significant pathogenetic role. PMID- 3093546 TI - Purification and characterization of the extracellular proteinase of Pseudomonas fluorescens NCDO 2085. AB - Pseudomonas fluorescens NCDO 2085 produced a single heat-stable extracellular proteinase in Na caseinate medium at 20 degrees C and pH 7.0. The proteinase was purified to electrophoretic homogeneity using chromatofocusing, gel filtration and ion-exchange chromatography. The purification procedure resulted in a 158 fold increase in the specific activity and a yield of 3.5% of the original activity. The enzyme is a metalloproteinase containing Zn and Ca, with an isoelectric point at 5.40 +/- 0.05 and a mol. wt of 40 200 +/- 2100. It is heat stable having D-values at 74 and 140 degrees C of 1.6 and 1.0 min respectively; 40 and 70% of the original activity remained after HTST (74 degrees C/17 s) and ultra high temperature (140 degrees C/4 s) treatments respectively. The amino acid composition of the proteinase was determined and compared with those from other Pseudomonas spp. PMID- 3093548 TI - Effects of cost containment on research and development. PMID- 3093547 TI - Resistance of Streptococcus lactis mutants to beta-lactam antibiotics. AB - Minimal inhibitory concentration and minimal bactericidal concentrations of penicillin and other beta-lactam antibiotics were determined for Streptococcus lactis in milk and trypteine soy broth. The values were always higher in milk than in broth. Minimal inhibitory concentration of penicillin was higher in solid than in liquid media. Two mutants resistant to penicillin and other beta-lactam antibiotics were obtained, and their growth rate, proteolysis, and acidification patterns determined. Tolerance toward these antibiotics was found when the mutants were grown in milk but not when they were grown in broth. PMID- 3093549 TI - Main nitrogen balance determinants in malnourished patients. AB - Factors influencing nitrogen balance during total parenteral nutrition have been investigated in 38 malnourished patients studied for a cumulative period of 280 days. According to multiple regression analysis, nitrogen intake (0.213 +/- 0.004 g kg-1 day-1, mean +/- SD) proved to be the major determinant of a positive nitrogen balance (0.018 +/- 0.004 g kg-1 day-1), followed by non-protein energy intake (43.3 +/- 0.5 kcal kg-1 day-1). Total calorie intake to predicted basal energy expenditure and non protein calorie to nitrogen ratios appeared to have little significance on nitrogen balance, when corrected for the two former variables. PMID- 3093550 TI - The future of health care delivery systems and settings. PMID- 3093551 TI - Continuity in change: power and gender in nursing. PMID- 3093552 TI - Dimensional stability of dental impressions after immersion disinfection. AB - Disinfection of dental impressions via short-term immersion in 0.5% or 1% sodium hypochlorite does not significantly affect the dimensional accuracy of the resultant casts. In addition, immersion in glutaraldehydes, povidone-iodine diluted in water, or halogenated phenol has no apparent effect on the dimensional stability of rubber impression materials. The results of this study support the use of immersion disinfectants for treatment of impressions for study models or removable dental appliances or prostheses. Coupled with the findings of other authors, the data suggest that such disinfection also would be suitable for rubber base and vinyl polysiloxane impressions for cast restorations. Given the need for infection control in the treatment of all dental patients, the results of this study support the recommendations of the American Dental Association for disinfection of dental impressions via immersion in an appropriate disinfectant solution. PMID- 3093553 TI - Effect of elevations of coronary artery partial pressure of carbon dioxide (PCO2) on coronary blood flow. AB - This study was designed to examine the effect of increases in the partial pressure of carbon dioxide (PCO2) in coronary artery blood on coronary blood flow, coronary reactive hyperemia and the coronary response to intracoronary adenosine administration. The left anterior descending coronary artery was cannulated and perfused over a wide range of perfusion pressure (P) and flow (F) with blood equilibrated with 0 to 40% carbon dioxide in 16 open chest dogs. Increases in coronary artery PCO2 from 20 +/- 2 to 93 +/- 8 to 211 +/- 22 mm Hg (mean +/- SEM) increased the coronary flow from 28 +/- 3 to 68 +/- 16 to 87 +/- 22 ml/min, respectively, at a perfusion pressure of 60 mm Hg and from 49 +/- 6 to 139 +/- 30 to 206 +/- 48 ml/min, respectively, at a perfusion pressure of 100 mm Hg. Coronary reactive hyperemia following a 30 second coronary perfusion line occlusion and the response to an intracoronary bolus of adenosine (60 micrograms) were prominent at a low PCO2 but absent at a high PCO2. Beta-adrenergic blockade did not abolish the increase in coronary flow that occurred at increased PCO2. Thus, progressive elevations of regional coronary PCO2 produced substantial increases in coronary blood flow and maximal or near maximal coronary vasodilation. PMID- 3093554 TI - Coronary thrombolysis: second chance therapy--maximizing the advantage. PMID- 3093555 TI - Coronary thrombolysis with tissue-type plasminogen activator (t-PA): emerging strategies. AB - Fundamental observations and the conceptual framework underlying coronary thrombolysis have a history dating back to 1789. Recent enthusiasm for it is predicated on the recently established safety of cardiac catheterization in critically ill patients, the high incidence of coronary thrombosis underlying acute transmural myocardial infarction and demonstrable benefit conferred to the heart and the patient when thrombolysis is initiated early after the onset of ischemia. Clot-selective activators of the fibrinolytic system offer promise for safe induction of coronary thrombolysis without marked predisposition to bleeding. One such activator, tissue-type plasminogen activator (t-PA), has been synthesized by recombinant deoxyribonucleic acid (DNA) technology, amenable to large scale production of pharmaceutical agents and hence widespread availability. Initial clinical trials conducted with t-PA have demonstrated opening rates of completely occluded, infarct-related coronary arteries of approximately 75% without marked depletion of fibrinogen. The focus of research in progress includes: noninvasive delineation of recanalization and estimation of the extent of myocardium salvaged by initial recanalization, development of alternative routes of administration of thrombolytic agents potentially exploitable by paramedical personnel and, perhaps, high risk patients themselves, and definitive elucidation of the extent to which benefits conferred by thrombolysis can be enhanced with adjunctive pharmacologic interventions as well as early angioplasty or surgery. PMID- 3093557 TI - Economics and ethics. PMID- 3093556 TI - Airway responses to hyperventilation of cold dry air: duration of protection by cromolyn sodium. AB - The magnitude and duration of the inhibitory effect of three doses of cromolyn sodium on the airway response to hyperventilation of cold dry air was examined in a double-blind, randomized controlled trial. Eight subjects with well controlled asthma were studied. On 4 separate days, doses of either 2 mg, 10 mg, 20 mg, or placebo were administered by metered-dose inhaler. Twenty minutes, 2 hours, and 4 hours after each medication, airway responsiveness to isocapnic hyperventilation of cold dry air was measured by use of a standardized dose-response method. At 20 minutes, all three doses inhibited bronchoconstriction, and there was no evidence of any difference in the magnitude of the inhibition between the doses. All three doses progressively provided less protection with time. By 2 hours, the inhibition induced by 2 mg was no longer different from placebo, and by 4 hours, only 20 mg still provided significant protection. The results demonstrate that, although the initial magnitude of inhibition may not be different between 2 mg and 20 mg, the rate at which the protective effect wears off is dose related. PMID- 3093558 TI - Adequacy of a modular tube feeding diet for burned patients. AB - Recent research on nutrition needs following thermal injury suggests that carbohydrate and caloric excess must be avoided while an attempt is made to meet relatively large protein requirements. The nutrition regimen in this investigation for adult and pediatric burned patients provides calories at twice the predicted basal metabolic rate, protein at 2.5 gm/kg/day, and carbohydrate at 5 mg/kg/minute. Lipids are provided to meet the caloric deficit after protein and carbohydrate administration. Even though such nutrients are readily provided parenterally, the high carbohydrate content of standard tube feedings makes it difficult to provide adequate protein without excess of carbohydrate and calories. As a result, a modular tube feeding, containing appropriate macro- and micronutrients and tailored to the individual patient, has been used in our burn units. The adequacy of the diet was assessed by the effect on nitrogen balance, weight change, selected serum indexes of visceral metabolism, and compliance with planned dietary goals. Patients remained in positive nitrogen balance more than 80% of the time while the modular diet was used in conjunction with other modes of therapy (parenteral and/or oral). More than 90% of the time, positive balance was achieved when the modular diet was used as the sole source of nutrition. Compliance with the caloric goal and physicians' diet orders for the modular diet exceeded, on average, the 80% level, which has previously been the established lower limit. The results in this study suggest that the modular diet is an appropriate method of nutrition support. PMID- 3093559 TI - [Echographic studies of the thickness of the endometrium during spontaneous and induced cycles: its application to in-vitro fertilization]. AB - The authors have estimated the thickness of the endometrium by measuring it ultrasonically between the 5th preovulatory and the 6th post-ovulatory day. This study, which was carried out as part of an in vitro fertilisation programme (IVF) was performed during 162 cycles of which 22 were spontaneous and 140 were stimulated by Clomiphene and HMG. The endometrium is significantly thicker and grows more rapidly when the cycles are stimulated. There is a correlation between the levels of progesterone in the blood and the thickness of the endometrium on the 2nd post-laparoscopy day. On the other hand there was no relationship between the thickness of the endometrium and with the development or otherwise of a pregnancy after replacing embryos. PMID- 3093560 TI - Effect of reduced uterine blood flow on fetal and maternal cortisol. AB - We have measured the changes in fetal and maternal plasma concentrations of cortisol in relation to blood gases and percent oxygen saturation during 2- and 4 h episodes of reversibly reduced uterine blood flow in sheep between 120 days gestation and term. During that period of reduced uterine blood flow there was a significant decrease in fetal arterial percent oxygen saturation (SaO2), PO2 and pH. Fetal SaO2 decreased from 59.5 +/- 3.2% to 31.8% +/- 2.8% by 15 min, 32.9 +/- 2.9% by 60 min, and 33.5 +/- 2.9% by 120 min. Fetal PO2 decreased from 3.2 +/- 0.1 KPa to 2.0 +/- 0.2 KPa by 15 min, 2.2 +/- 0.2 KPa by 60 min and 2.3 +/- 0.1 KPa by 120 min. Fetal pH decreased from 7.36 +/- 0.01 to 7.30 +/- 0.03 by 15 min, 7.27 +/- 0.02 by 60 min and 7.25 +/- 0.03 by 120 min. During the period of reduced uterine blood flow, fetal plasma concentrations of cortisol increased from 37.1 +/- 10.8 nmol/l to 53.3 +/- 9.2 nmol/l by 15 min, 49.2 +/- 11.4 nmol/l by 60 min and 43.3 +/- 9.0 nmol/l by 120 min. The greatest percentage increase in fetal plasma concentrations of cortisol occurred in fetuses of 126-139 days gestation. There was no significant change in maternal blood gases, SaO2 or plasma concentrations of cortisol. These experiments demonstrate that there is a significant increase in fetal plasma concentrations of cortisol in response to reductions in uterine blood flow from as early as 120 days gestation. PMID- 3093561 TI - Screening for Clostridium difficile in chronic inflammatory bowel disease in relapse. Is it helpful? Is it cost efficient? PMID- 3093562 TI - Phenytoin hypersensitivity hepatitis and mononucleosis syndrome. AB - We present a patient who developed a mononucleosis syndrome 6 weeks after starting phenytoin therapy for a seizure disorder. Improvement followed initial discontinuation of the phenytoin, but near-fatal hepatic necrosis resulted from intravenous phenytoin rechallenge. A serious reaction with a 18% overall mortality, phenytoin hepatitis may closely resemble infectious mononucleosis with fever, pharyngitis, lymphadenopathy, and atypical lymphocytosis. Continued administration of phenytoin or later rechallenge may increase the severity of the reaction. PMID- 3093563 TI - Quantitative wing variation in inbred and outbred lines of Drosophila melanogaster. AB - Variation of two wing morphology characters was studied in 11 X-chromosome substitution lines and three outbred lines of D. melanogaster, as a test of quantitative genetic predictions regarding variance components and heritabilities. As expected from inbreeding of the lines, between-lines components of phenotypic variance are statistically significant, while the significant within-line component is attributable to a maternal effect. Unusually low broad-sense heritabilities were observed in the inbred lines, and unusually low narrow-sense heritabilities were observed in the outbred lines. Low heritability estimates cannot be explained by insensitive measurement techniques, since the techniques were sufficiently sensitive to detect significant maternal effects. The most likely explanation for the low heritability estimates is the operation of natural selection on wing or correlated characters as stocks adapt to the laboratory environment. PMID- 3093564 TI - Afferent connections of the substantia innominata/basal nucleus of Meynert in carnivores and primates. AB - Afferent connections to the substantia innominata/nucleus basalis complex of monkeys and cats were traced by using the method of retrograde transport of horseradish peroxidase (HRP). Altogether ten injections of HRP were performed in four monkeys (Saimiri sciureus, Callithrix jacchus, Galago senegalensis) and in four cats, with either vertical or oblique needle approaches. The entire brains excluding the olfactory bulbs and the cerebellum were then screened for labeled neurons. In both monkey and cat brains, many retrogradely labeled neurons could be detected in the amygdala, hypothalamus, midline thalamus, zona incerta, and the fields of Forel. Further but weaker labeling occurred in the medial septal nucleus, diagonal band of Broca, olfactory tubercle, paraventricular, anterior, mediodorsal, and central lateral thalamic nuclei, lateral habenula, ventral tegmental area of Tsai, interpeduncular nucleus, parabrachial, raphe, dorsal tegmental nucleus and the locus caeruleus. Cortically, prefrontal, insular, entorhinal, prepiriform, and periamygdaloid areas of both species showed considerable labeling as well as the whole temporal lobe of the monkeys used. The perirhinal and basal temporal cortex of all cats showed moderate labeling. In both monkeys and cats, extremely scarce labeling occurred within the cingulate, retrosplenial, and subicular cortex. From an anatomical point of view, the manifold connections of the substantia innominata/basal nucleus of Meynert found in this study underscore the participation of these nuclear groups in motivational, emotional, and cognitive (e.g. mnemonic) functions. Considering the widespread cortical efferents of this complex, it is suggested that the substantia innominata/nucleus basalis of Meynert serves the transmission of information arising within the limbic system to the whole neocortex. PMID- 3093565 TI - In vivo thymocyte maturation. BUdR labeling of cycling thymocytes and phenotypic analysis of their progeny support the single lineage model. AB - Spontaneously cycling thymocytes have been labeled in vitro and in vivo by bromodeoxyuridine (BUdR), a non-reutilized precursor of DNA that is detectable by a monoclonal antibody. Studies of BUdR-labeled cells have included the determination of their anatomical location, size, and nuclear aspects and of their cell surface phenotype. Dividing blasts were initially located in the cortex (mainly but not exclusively in the subcapsular region) and expressed the double-negative (Lyt-2- L3T4-) and double-positive (Lyt-2+ L3T4+) phenotypes. The fate of these cells have been determined in days after BUdR administration, and we observed an initial double-negative to double-positive transition that was followed by the death of the majority of labeled cells in the cortex. As of day 3, the few surviving cells acquired a mature helper phenotype (Lyt-2- L3T4+) and began migrating into the thymic medulla. The exclusive medullary location of blast cell progeny was observed between days 5 and 10 post-BUdR administration. These results suggest a direct precursor-product relationship between dividing cortical cells and mature medullary thymocytes, and therefore support the single lineage model of intrathymic differentiation. PMID- 3093566 TI - Anti-interleukin 2 receptor antibody suppresses delayed-type hypersensitivity to foreign and syngeneic antigens. AB - Delayed-type hypersensitivity (DTH) requires stimulation of antigen-specific helper T cells (Th). Because de novo expression of the interleukin 2 receptor (IL 2R) is a necessary step in T cell activation, we tested the capacity of anti mouse IL 2R monoclonal antibody (Mab) and anti-Th Mab (anti-L3T4) to block DTH. We examined the effect of these Mab on two distinct DTH systems, i.e., to foreign hapten (trinitrobenzenesulfonic acid) and to this hapten present on syngeneic blasts. Both anti-IL 2R and anti-L3T4 Mab suppress DTH. Therapy is as effective treating with one injection just before challenge with the hapten as giving six daily injections. These data indicate that DTH is dependent on a discrete subset of activated IL 2R-positive T cells, because anti-IL 2R therapy, which targets few cells, is as effective as anti-L3T4 Mab treatment, which targets the entire Th subset. PMID- 3093567 TI - Characterization of the cell surface receptors for human B cell growth factor of 12,000 molecular weight. AB - Quiescent normal human B cells have been shown to require an activation step before proliferating in response to B cell growth factor (BCGF) of 12,000 m.w. (12 kd). One effect of cell activation has been the putative acquisition of specific cell surface growth factor receptors. In this report, the existence of such receptors has been confirmed by using purified radioiodinated BCGF-12 kd. BCGF-12 kd receptors on activated B cells have been shown to be distinct form those interacting with IL 2. Scatchard analysis revealed both high affinity receptor sites with an apparent Kd of 28.6 pM and low affinity receptor sites with Kd of 1.2 nM on freshly prepared, anti-IgM activated peripheral blood B cells. Human B cells grown in culture for extended periods of time in the presence of BCGF-12 kd also displayed high affinity receptor sites (Kd, 41.4 pM) and low affinity receptor sites (Kd, 0.9 nM). The action of BCGF-12 kd therefore appears to be mediated by binding to its lineage-specific receptors on the cell surface. PMID- 3093568 TI - BSF-1 action on resting B cells does not require elevation of inositol phospholipid metabolism or increased [Ca2+]i. AB - B cell stimulatory factor-1 (BSF-1) acts on resting B cells to increase expression of class II major histocompatibility complex (MHC) molecules and to prepare for more prompt entry into S phase in response to anti-IgM and lipopolysaccharide. It also acts as a costimulant, with low concentrations of anti-IgM, to cause resting B cells to synthesize DNA. Unlike anti-IgM, BSF-1 does not cause elevation in inositol phospholipid metabolism or in concentration of intracellular free calcium, nor does it enhance such biochemical responses to anti-IgM. Furthermore, increased expression of class II MHC molecules to BSF-1 is observed when essentially all extracellular calcium is chelated by EGTA, whereas lower concentrations of EGTA completely inhibit increases in class II molecules in response to anti-IgM. These results indicate that BSF-1 effects on resting B cells are not mediated by the inositol phospholipid metabolic pathway. PMID- 3093569 TI - In vivo and in vitro expression of an interleukin 2 receptor by murine B and T lymphocytes. AB - Interleukin 2 (IL 2), which is well established to be a T cell growth factor, has more recently been shown to stimulate B lymphocyte growth and differentiation in vitro. Responsiveness of B and T cells to IL 2 has been associated with expression of a cell membrane IL 2 receptor (IL 2R). To investigate the role of IL 2 in B cell growth and differentiation in vivo, a system was used in which the injection of mice with a goat antibody to mouse IgD (GaM delta) induces polyclonal T-independent B cell proliferation first, and later induces polyclonal T-dependent B cell proliferation and IgG secretion. IL 2R expression by splenic B and T lymphocytes from GaM delta injected mice was studied by a dual label immunofluorescence technique. Although GaM delta was found to be a strong inducer of B cell IL 2R expression in vitro, even in serum-free medium, and stimulated up to 50% of splenic T cells to express considerable quantities of IL 2R in vivo, it failed to induce more than minimal B cell IL 2R expression in vivo. Concanavalin A and bacterial lipid A also induced B cells to express IL 2R to a much greater extent in vitro than in vivo. Although these agents and GaM delta acted synergistically to stimulate B cell IL 2R expression both in vitro and in vivo, a single agent induced B cell IL 2R expression to a considerably greater extent in vitro than did all three agents acting together in vivo. In vitro GaM delta induced B cell IL 2R expression was not suppressed by inclusion of IL 2 in the culture medium but was suppressed by the presence of 10% normal mouse serum or plasma. These observations suggest that polyclonal T-dependent B cell proliferation and antibody secretion may not require an interaction between B cells and IL 2; the in vivo environment may downregulate IL 2R expression by B cells: and in vivo B cell IL 2R expression and consequently, induction of B cell responsiveness to IL 2, may require stimuli beyond those sufficient to induce B cell IL 2R expression and IL 2 responsiveness in vitro. PMID- 3093570 TI - Proliferation in vitro and interleukin production by 14 day fetal and adult Lyt-2 /L3T4- mouse thymocytes. AB - When 14 day fetal mouse thymocytes, which are phenotypically Lyt-2-/L3T4-(2-4-), were stimulated in vitro with a combination of phorbol myristate acetate (PMA) and the calcium ionophore ionomycin, they proliferated without addition of exogenous interleukins and/or growth factors. Addition of exogenous IL 2 resulted in a slight enhancement of fetal thymocyte proliferation. By using factor dependent indicator cell lines, this proliferation was shown to be accompanied by the production of IL 2 and IL 3. However, phenotypic analysis by using flow microfluorometry and monoclonal antibodies to Lyt-2 and L3T4 showed little differentiation among proliferating 2-4-fetal thymocytes. Interestingly, the in vitro growth of PMA + ionomycin-stimulated fetal thymocytes appeared to be IL 2 dependent in that it was inhibited by a monoclonal antibody to the IL 2 receptor. The results obtained with fetal thymocytes were compared with those obtained when using 2-4- thymocytes from adult mice. PMID- 3093571 TI - The valence for ligand of the human mononuclear phagocyte 72 kD high-affinity IgG Fc receptor is one. AB - The valence for ligand of the 72 kD high-affinity IgG FcR present on human mononuclear phagocytes was evaluated. Lysates of U937 cells whose high-affinity FcR had been saturated with equivalent quantities of 125I-IgG1 kappa and unlabeled IgG1 lambda or with 125I-IgG1 lambda and unlabeled IgG1 kappa were incubated with Sepharose-anti-kappa. Eighty-nine percent of the applied 125I-IgG1 kappa was bound, whereas 0.35% of the applied 125I-IgG1 lambda bound (mean of two experiments), indicating that if the receptors are occupied with ligand, the receptors bind only one ligand molecule at a time. Two experiments were performed to show that the receptors were ligand-occupied. First, a monoclonal antibody directed against the 72 kD FcR (FcRmab32) was added to lysates of U937 cells saturated with equal quantities of 125I-IgG1 lambda and IgG1 kappa. This anti-FcR antibody caused a dose-dependent sevenfold increase in the amount of 125I-IgG1 lambda bound to the anti-kappa immunoadsorbent (presumably by cross-linking receptors bearing 125I-IgG1 lambda with receptors bearing IgG1 kappa), whereas monoclonal antibodies (MMA and IV3) directed against two other determinants on U937 caused no such increase. In the second experiment, Sepharose-FcRmab32 adsorbed 60% of the 125I-IgG1 kappa and 46% of the 125I-IgG1 lambda applied in a U937 lysate (bearing high-affinity FcR), whereas only 3% of 125I-IgG1 kappa and 6% of 125I-IgG1 lambda applied in a K562 lysate (bearing no high-affinity FcR) were adsorbed. We interpret these data to indicate that in detergent solution the valency of the high-affinity FcR on U937 cells is one. PMID- 3093572 TI - L3T4+ T lymphocytes play a major role in the pathogenesis of murine cerebral malaria. AB - The pathogenic importance of L3T4+ T cells in the development of murine cerebral malaria was demonstrated by the following observations. First, in vivo administration of an anti-L3T4 monoclonal antibody protected Plasmodium berghei infected CBA mice from the development of neurologic symptoms and acute death. In contrast, injection with an MAb directed against the Ly.2+ T cell subset had no protective effect. Second, thymectomized, irradiated, and bone marrow reconstituted (ATxBM) CBA mice did not develop acute cerebral malaria when infected by P. berghei, although parasitemia and anemia rose to the same extent as in normal P. berghei-infected CBA mice. The occurrence of lethal neurologic perturbations could be restored in ATxBM mice selectively reconstituted with L3T4+ Ly.2-lymphocytes but not with Ly.2+ L3T4- cells. Third, adoptive transfer of L3T4+ cells from mice dying of cerebral malaria into euthymic mice subsequently infected by P. berghei led to an acceleration of the disease. These results confirm that cerebral malaria in mice is the expression of immunopathologic reactions and outline the particular pathogenic importance of L3T4+ T cells. PMID- 3093573 TI - Gene transfer of immunoglobulin light chain restores heavy chain secretion. AB - Several lines of evidence suggest that immunoglobulin (Ig) light (L) chain plays a role in the secretion of heavy (H) chain. For example, myeloma variant lines, which synthesize the Ig H chain but not the L chain, fail to secrete H chain protein. Here we have tested directly the role of chain assembly in the control of Ig secretion by the transfer of functional L chain genes into two such L chain defective myeloma mutants. A lambda 2 or kappa L chain gene was introduced into variant lines of the mouse myelomas MOPC 315 (IgA, lambda 2) or PC7 (IgM, kappa), respectively. Although the two mutant lines are unable to secrete the H chain they produce, rescue of secretion of complete Ig protein molecules (IgA or IgM) was observed after transfection. These results imply that the secretory apparatus of these cells is intact and that the failure to secrete free H chain reflects a structural feature intrinsic to that protein. The implications of these results with respect to control of secretion of multi-subunit proteins are discussed. PMID- 3093574 TI - Role of protein kinase C and intracellular calcium mobilization in the induction of macrophage tumoricidal activity by interferon-gamma. AB - These studies were designed to test the hypothesis that changes in intracellular Ca2+ levels and activation of the calcium ion- and phospholipid-dependent protein kinase C were required for the induction of macrophage tumoricidal activity by interferon-gamma (IFN-gamma). Phenothiazines and R24571, known antagonists of calcium-binding proteins and therefore nonspecific inhibitors of protein kinase C, blocked in a dose-dependent manner the induction of macrophage cytocidal activity by either natural or recombinant IFN-gamma. Macrophages depleted of intracellular Ca2+ by chelation with Quin 2, were also unresponsive to IFN-gamma. These treatments effected neither the binding of IFN-gamma to its cell surface receptor nor the normal intracellular processing of IFN-gamma. Activators of protein kinase C (such as phorbol esters) and Ca2+ ionophores when added alone did not effect the activation state of the macrophage population. However, macrophages exposed to both drugs in combination were elevated into the primed activation state such that in the presence of a second signal (lipopolysaccharide or heat killed Listeria monocytogenes), the cells were triggered to express full levels of tumoricidal activity. The capacity of phorbol esters to induce cellular activation correlated with their ability to bind and to activate protein kinase C. No synergistic effect was observed between IFN-gamma and protein kinase C activators and/or Ca2+ ionophores, indicating that the drugs could only prime and could not trigger macrophages for tumor cell killing. These results thus support the concept that protein kinase C activation and mobilization of intracellular Ca2+ are essential steps in the pathway of IFN-gamma-dependent induction of non specific tumoricidal activity in macrophages. PMID- 3093575 TI - Effects of 5-fluorouracil on B lymphocyte lineage cells. AB - The aim of these studies was to determine the sensitivity of B lymphocyte lineage precursor cells in mice to 5-fluorouracil (5-FU). Selective effects could be very helpful in dissecting precursor-product relationships between these and the rare multipotential stem cells from which they derive. Numbers and functions of particular types of cells were determined at intervals after a single treatment (3 mg) and, as expected, myeloid-committed stem cells were very severely affected. Day 8 spleen colony-forming cells (CFU-S) and colony-stimulating factor responsive macrophage progenitors were reduced by 98% within 24 hr, whereas presumptive early stem cells (day 14 CFU-S) were much more resistant. B cells, which were probably recently formed in bone marrow and which are not thought to be actively dividing, were also 5-FU-sensitive, but perhaps less so than pre-B cells and immunoglobulin-negative lymphocytes bearing a B lineage marker. Approximately 5 wk were required for the normal cellular composition of marrow to return to normal. Transplantation of marrow from 5-FU-treated mice suggested that the slow regeneration of B lymphocytes might partially result from residual drug effects or damage to microenvironmental elements which are required for B lineage differentiation. Acute reductions of lymphocytes in the thymus were also documented, and the larger cells declined most rapidly and regenerated most slowly in that tissue. Of particular interest was the differential susceptibility of B cells in various lymphoid tissues to 5-FU. Whereas lymph node B cells were minimally affected, one-half of the splenic B cells disappeared within 48 hr of drug injection. Intrinsic differences in 5-FU sensitivity were confirmed by treatment of lymphocytes in vitro, and this suggests that particular B cell sets may be metabolically distinct. This drug should find additional experimental application in studies of B lymphocyte formation and functional heterogeneity. PMID- 3093576 TI - Bacterial activation of human natural killer cells. Characteristics of the activation process and identification of the effector cell. AB - We showed previously that contact of human peripheral blood lymphocytes with glutaraldehyde-fixed Salmonella bacteria augmented their cytotoxic capacity against NK-sensitive targets. We have now analyzed the characteristics of the activation and also identified the subsets of lymphocytes responding to bacterial contact. Blocking of protein synthesis with cyclohexamide totally abrogated bacterial induction of activated killing (AK), whereas inhibition of DNA synthesis with mitomycin C did not significantly affect the capacity of lymphocytes to respond to bacterial contact. Both the induction and the effector phase of AK were radioresistant. The AK cells exhibited efficient lytic activity, comparable to that induced by recombinant IL 2 (rIL 2), against NK-resistant targets (including both hematopoietic and solid tumor cell lines). All inducible cytotoxic activity was contained within the subset of lymphocytes expressing Leu 19 (NKH-1) antigen. Leu-19- lymphocytes exhibited no significant NK activity and could not be further stimulated by bacterial contact, rIL 2, or IFN-alpha. Within the Leu-19+ lymphocyte subset, two distinct cell types were present; CD3-, Leu 19+ NK cells and CD3+. Leu-19+ T cells. The CD3+, Leu-19+, T cells mediated low levels of non-MHC-restricted cytotoxicity against K562, but did not respond to bacterial contact, even though rIL 2 could augment their lytic activity slightly. However, the cytotoxic activity of CD3-, Leu-19+ NK cells was significantly augmented by bacterial contact. Within the CD3-, Leu-19+ NK cell population both CD16+ and CD16- cells responded to bacterial activation. The CD3-, CD16-, Leu-19+ cells constituted 1 to 4% of the Percoll-fractionated low buoyant density lymphocytes and accounted for the activation seen within the CD16- lymphocyte population. Thus bacterial stimulation of NK activity seems to be mediated for the most part via CD16+, Leu-19+ cells, and a minor overall contribution is mediated via CD3-, CD16-, Leu-19+ cells. No apparent involvement of T cells was seen in the lytic response of lymphocytes to bacterial contact. PMID- 3093577 TI - Proliferation of T lymphocytes in response to interleukin 2 varies with their state of activation. AB - The interleukin 2 (IL 2) receptor on T lymphocytes can be upregulated by a variety of stimuli including antigen, lectin, and IL 2 itself. In this report, the direct binding of radiolabeled IL 2 and a quantitative bioassay of T cell responsiveness to IL 2 were used to determine the biological significance of upregulation of the murine IL 2 receptor. Antigen and lectin, and to a lesser extent IL 2, were found to cause an increase in the expression of the high affinity form of the IL 2 receptor on both a T cell clone and concanavalin A induced T cell blasts. A 2-day stimulation with antigen resulted in an increase in the sensitivity of the T cell clone to IL 2, whereas activation with IL 2 caused a decrease in the sensitivity of these cells to subsequent stimulation with IL 2. Comparison of the direct binding and the functional data revealed that IL 2-preactivated T cells required a greater number of occupied high affinity IL 2 receptors to achieve a given fractional response than did unactivated T cells. These observations suggest that the sensitivity with which a T cell responds to IL 2 is not determined solely by the number of high affinity IL 2 receptors it bears. PMID- 3093578 TI - Functional status of interleukin 2 receptors expressed by immature (Lyt-2-/L3T4-) thymocytes. AB - A subpopulation of phenotypically immature (Lyt-2-/L3T4-) thymocytes express receptors for the polypeptide hormone interleukin 2 (IL 2); however, these cells do not proliferate in vitro in response to IL 2. In investigating this phenomenon in greater detail, we observed that the IL 2 receptors (IL 2-R) on freshly isolated immature thymocytes bound IL 2 with about fivefold lower affinity (Kd approximately 100 pM) than IL 2-R on activated mature T cells and T cell lines (Kd approximately 20 pM). Furthermore, in contrast to activated T cells, Lyt-2 /L3T4- thymocytes did not endocytose bound IL 2. When stimulated in short-term culture with a combination of phorbol ester (PMA) and calcium ionophore, Lyt-2 /L3T4- thymocytes proliferated in a largely IL 2-dependent fashion. IL 2-R expression on these activated cells initially disappeared (at 24 hr) and subsequently reappeared (at 48 to 72 hr). Reexpressed IL 2-R on activated thymocytes resembled those on mature T lymphocytes in that they bound IL 2 with high affinity (Kd = 15 to 25 pM) and were capable of endocytosing IL 2. Taken together, these data place certain constraints on the putative physiologic role of IL 2 in intrathymic growth regulation. PMID- 3093579 TI - The intracellular retention of newly synthesized platelet-activating factor. AB - The ether phospholipid platelet-activating factor (PAF) has been generally assumed to be released into the extracellular environment by the cells of origin, whereupon it effects its well-known mediator functions. However, during the generation of PAF by human neutrophils, it was noted that the majority of the measurable PAF remained associated with the cells. Accordingly, the intracellular and extracellular distribution of PAF was examined in neutrophils and several other cell types. No PAF was detected in association with unstimulated neutrophils. However, in stimulated neutrophils, PAF was produced and the majority of this material remained in association with the cells independent of the type of stimulus, dose of stimulus, or method of cell isolation used. This pattern of cell association of PAF was seen in all but one of the cell types tested. The retention of PAF by stimulated neutrophils was not due to spurious underestimates of the extracellular levels due to extracellular metabolism and inactivation of released PAF, nor to release followed by readsorption or binding of PAF to the cells. The retention of PAF also occurred in the presence of plasma and appears to be a common phenomenon. Thus, the majority of newly synthesized PAF appears to be retained within the cell and not released. PMID- 3093580 TI - Interferon-gamma-activated human monocytes inhibit the intracellular multiplication of Legionella pneumophila. AB - We have examined the interaction between interferon-gamma (IFN-gamma)-activated human monocytes and Legionella pneumophila, the agent of Legionnaires' disease. Human monocytes activated with human recombinant IFN-gamma inhibit the intracellular multiplication of L. pneumophila. The degree of inhibition is proportional to the concentration of IFN-gamma, and maximal inhibition consistently occurs with greater than or equal to 2 micrograms/ml. Monoclonal anti-IFN-gamma antibody completely neutralizes the capacity of IFN-gamma to activate monocytes. Monocytes infected 24 hr after explantation maximally inhibit L. pneumophila multiplication if treated with IFN-gamma before infection or up to 2 hr after infection; treatment 6 hr or more after infection results in submaximal inhibition. Monocytes infected 48 hr after explantation inhibit L. pneumophila multiplication maximally if treated with IFN-gamma up to 12 hr before infection, but submaximally if treated at the time of infection. Once activated, monocytes inhibit L. pneumophila multiplication in the absence of IFN-gamma in the culture. Strikingly, monocytes maximally inhibit L. pneumophila multiplication after treatment with IFN-gamma for as briefly as 1 hr before infection. In the absence of anti-L. pneumophila antibody, neither IFN-gamma activated monocytes nor nonactivated monocytes kill L. pneumophila. In the presence of specific antibody and complement, IFN-gamma-activated monocytes kill a proportion (0.5 log) of an inoculum but not more than nonactivated monocytes. L. pneumophila forms a specialized phagosome in IFN-gamma-activated monocytes that does not differ ultrastructurally from the L. pneumophila phagosome in nonactivated monocytes. These results demonstrate that IFN-gamma can activate human monocytes to exert a potent antimicrobial effect against a highly virulent intracellular bacterial pathogen. These findings extend previous observations on interactions between activated mononuclear phagocytes and L. pneumophila, and additionally support the hypothesis that cell-mediated immunity plays a major role in host defense against L. pneumophila. PMID- 3093581 TI - Isotype concentrations of human antibodies to group A meningococcal polysaccharide. AB - Antibodies to meningococcal group A polysaccharide (MenA) in the sera of 34 vaccinated adults were quantitated by an isotype-resolving solid-phase RIA (IgA, IgM, IgG1, IgG2, IgG3, and IgG4). All individuals had antibodies before vaccination. The geometric mean concentration was 2.9 micrograms/ml. Two weeks after vaccination the mean antibody concentration had trebled. Average proportions of the three isotypes were then as follows: IgA 15%, IgM 48%, IgG 37%. No differences were found between individuals who had been immunized with the polysaccharide 7 to 8 yr earlier and "primary responders." The subclass composition of IgG antibodies was determined in the 24 postvaccination samples with a definite IgG response (greater than 2-fold increase). IgG1 was the predominant subclass in antibodies of some sera and IgG2 in others, but the average proportions of both subclasses were nearly the same. IgG3 and IgG4 were only found in occasional sera, but when present, each subclass accounted for up to 6%. Although the ratio of kappa and lambda chains could not be determined, there was evidence to suggest that it was higher in anti-MenA antibodies than in antibodies to protein antigens. PMID- 3093582 TI - Corticosteroid-resistant bone marrow-derived B lymphocyte progenitor for long term in vitro cultures. AB - A long-term in vitro culture system derived from murine bone marrow cells can successfully support the growth of B cell precursors, pre-B cells, and IgM expressing B cells. Intermediates in the B cell developmental pathway are known to have differential sensitivities to the toxic effects of corticosteroids. We demonstrate here that long term B lineage cultures can be established with the corticosteroid-resistant cell population from bone marrow. Kinetics for the establishment and growth of cultures derived from corticosteroid-treated marrow are similar to those observed with control cultures. Cells obtained from both sets of cultures have similar morphologies and ranges of phenotypic markers. These results indicate that the cell responsible for the outgrowth of the long term B lineage cultures is corticosteroid resistant and is likely to be earlier in the B lymphocyte lineage than steroid-sensitive pre-B cells. PMID- 3093583 TI - Two-color flow cytometry and functional analysis of lymphocytes cultured from human renal allografts: identification of a Leu-2+3+ subpopulation. AB - The phenotype of T lymphocyte subsets present in renal biopsies showing acute cellular allograft rejection in six patients on cyclosporine have been characterized in situ by immunoperoxidase staining, and after expansion in vitro in interleukin 2 (IL-2) by two-color flow cytometry, sorting, and functional analysis. After 8 to 42 days in organ culture, both Leu-3+ (CD4) and Leu-2+ (CD8) subsets were found in each culture, in a ratio that varied from 0.2 to 5.0, which was not significantly different than the results of in situ immunoperoxidase staining of the uncultured biopsy. The cultured cells were almost all Leu-4+ (CD3) T cells (89% +/- 4), which expressed the activation markers DR (82% +/- 6) and the IL 2 (CD25) receptor (15% +/- 4). The Leu-3+ cells were largely Leu-8- (90% +/- 6), whereas a minority of the Leu-2+ cells were Leu-15+ (CD11) (26% +/- 4). Only a small fraction of the Leu-2+ cells stained for Leu-7 (8% +/- 6). Functional analysis of FACS-purified Leu-2-3+ and Leu-2+3- populations indicated that both subsets proliferated in response to graft donor antigens in a mixed lymphocyte reaction (MLR) and produced IL 2. Only the Leu-2+3- population demonstrated donor-specific cytotoxic activity. A minor subpopulation in each culture were both Leu-3+ and Leu-2+ (2.0%). Leu-2+3+ cells from one biopsy were purified to homogeneity (99.8%), and were found to express the T cell antigen receptor complex Ti/CD3 (WT-31+, Leu-4+), but not the common thymocyte antigen CD1 (OKT6). The Leu-2+3+ cells neither responded in the MLR, nor showed any cytotoxic capacity. The Leu-2+3+ cells were capable of IL 2 but not interferon gamma production. None of the purified cultures demonstrated NK activity. A subset of the purified Leu-2+3+ cells lost Leu-2+ during 1 to 3 wk in culture, and became Leu-2-3+. These studies provide evidence that the cells that infiltrate renal allografts during rejection include alloproliferative, lymphokine-producing cells of both Leu-2+ and Leu-3+ subsets. The Leu-2+3- cells are also highly cytotoxic against donor lymphocytes, indicating the presence of helper independent cytotoxic T cells. A minor population of Leu-2+3+ T cells that do not express donor specific function was also identified. PMID- 3093584 TI - Immune interferon enhances the production of interleukin 1 by human endothelial cells stimulated with lipopolysaccharide. AB - Interferon-gamma (IFN-gamma) is a macrophage-activating factor that has also been shown to act on endothelial cells (EC). Interleukin 1 (IL 1), first described as a monocyte product, is also produced by EC after stimulation by lipopolysaccharide (LPS). In this study, the effect of IFN-gamma on the release of IL 1 by EC stimulated with LPS has been investigated. Although IFN-gamma did not stimulate the release of IL 1 or increase the apparent intracellular pool of IL 1 when incubated with EC, there was an increase in the amount of IL 1 released when cells preincubated with IFN-gamma were stimulated with LPS. The effect of IFN-gamma increased with concentration (1 to 1000 U/ml) and with duration of preincubation (24 to 96 hr). The presence of IFN-gamma was not required during the stimulation with LPS. When EC were cultured without IFN-gamma for increasing time periods up to 96 hr, the amount of IL 1 released by EC on subsequent stimulation with LPS progressively decreased. Addition of as little as 1 U/ml of IFN-gamma, however, prevented the loss in capacity of EC to secrete IL 1 when stimulated with LPS. In vivo, EC are involved in the emigration of mononuclear cells from the blood to inflammatory sites. Because IL 1 is chemotactic for lymphocytes and also increases the binding of lymphocytes to EC, activation of EC by T cell-derived factors such as IFN-gamma may augment lymphocyte emigration by increasing the release of IL 1 at the blood-tissue interface. PMID- 3093585 TI - Effects of interferon-gamma and tumor necrosis factor-alpha on the expression of an Ia antigen on a murine macrophage cell line. AB - Cultures of the murine myelomonocytic cell line, WEHI-3, can be induced to express the Class II MHC antigen, I-A, by incubation with rMuIFN-gamma and/or rHuTNF-alpha. A 24-hr incubation with the combination of rMuIFN-gamma (5.6 ng/ml) and rHuTNF-alpha (13 ng/ml) induced the highest level of expression in the cell population (more than 90%), followed by rMuIFN-gamma (75%) and rHuTNF-alpha (33%). Comparison of the level of mRNA for the heavy chain subunit of the I-A molecule, A alpha, indicates that the combination is 10 and 40 times as stimulatory as rMuIFN-gamma and rHuTNF-alpha alone, respectively. Each cytokine treatment induced a time-dependent increase in the level of A alpha mRNA over the 72 hr of incubation examined, although the combination continued to elevate the level of A alpha mRNA above that induced by either cytokine alone. The findings reported here demonstrate that the monokine rHuTNF-alpha can induce I-A antigen expression and A alpha mRNA. Furthermore, stimulation by the combination of rHuTNF-alpha and rMuIFN-gamma is more than additive, relative to the effects of each cytokine as individual agents. PMID- 3093586 TI - Analysis of cytostatic/cytotoxic lymphokines: relationship of natural killer cytotoxic factor to recombinant lymphotoxin, recombinant tumor necrosis factor, and leukoregulin. AB - Previous results that were obtained by using supernatants from the co-culture of human peripheral blood lymphocytes and the natural killer susceptible cell line K562 strongly inhibited the growth of various tumor cell lines. No correlation was observed between the susceptibility of the target cell lines to growth inhibition and to lysis by natural killer cells. Rather the spectrum of cytostatic activity and the characteristics of the soluble factor were similar to those of leukoregulin (LRG), a recently described lymphokine. Because of the recent availability of recombinant tumor necrosis factor (TNF) and lymphotoxin (LT), we compare the target selectivity and mechanism of action of these (TNF, LT, LRG) factors with natural killer cytotoxic factor (NKCF). The pattern of target cell susceptibility to growth inhibition or cytolysis by the factors were quite distinct from the pattern observed when cells were exposed to NKCF. Furthermore, antibodies to rLT or rTNF had no effect on LRG cytostasis or NKCF lysis, arguing against a requirement for or synergistic interaction with low levels of LT or TNF. Some of the targets susceptible to LRG were growth inhibited but were not lysed, thereby distinguishing it from NKCF. Furthermore, LRG cytostasis was not inhibited by mannose-6-PO4 or rabbit antibodies to granule cytolysin, both of which block natural killer cytotoxic factor. Therefore, LRG appears to be a cytostatic factor produced by large granular lymphocytes in response to K562 that is distinct from NKCF, TNF, and LT. In addition, NKCF, rLT, rTNF, and LRG, although having cytotoxic/cytostatic activity, are distinct functional factors and may represent a family of lytic factors. PMID- 3093587 TI - Growth inhibition of Candida albicans by human polymorphonuclear neutrophils: activation by interferon-gamma and tumor necrosis factor. AB - This study was designed to determine whether anti-fungal activity in human polymorphonuclear neutrophils (PMN) might be under the regulation of cytokines such as tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma). By using a radiolabel microassay developed in our laboratory that makes use of the incorporation of [3H]glucose into residual candida, we demonstrated that PMN were better able to inhibit Candida albicans growth in vitro than peripheral blood lymphocytes (PBL). PMN from normal volunteers added to C. albicans for 24 hr at 37 degrees C in a 96-well microplate inhibited fungal growth almost completely at the 300:1 effector/target ratio and frequently at 100:1. Significant activity was still detected at 10:1. In contrast, PBL from the same donors had less activity than PMN at all the ratios tested and lost all function at the 30:1 ratio. TNF and IFN-gamma added to the PMN/candida cultures additionally enhanced PMN to inhibit candida growth. Both cytokines effectively activated PMN down to 0.1 to 0.01 U/ml, and neither cytokine interfered directly with fungal growth, even up to 1000 U/ml. Concentrations of TNF and IFN-gamma below the level that enhanced PMN function when added together to PMN acted synergistically to significantly enhance their anti-fungal activity. Therefore, TNF and IFN-gamma which are active on lymphoid cells, also appear to have the ability to directly activate PMN, and the synergistic action of the two cytokines at low doses that may be below the toxic range may prove to be of clinical importance in protection of immunocompromised host against opportunistic infections. PMID- 3093588 TI - Cellular immune response to human sarcomas: cytotoxic T cell clones reactive with autologous sarcomas. I. Development, phenotype, and specificity. AB - Human T cell clones cytotoxic for autologous sarcoma cell lines have been developed from patient JM with an osteogenic sarcoma, and from patients EG and RM with malignant fibrohistiocytoma. These clones were derived from the cocultivation of peripheral blood lymphocytes (PBL) with the respective patient's autologous irradiated established tumor cell lines (AIT). After two cycles of stimulation for 5 days in bulk culture, these "educated" lymphocytes were seeded at a density of 1 X 10(6) cells/well in 24-well plates and were cultured in the presence of highly purified natural IL 2 and AIT, the latter serving as a feeder layer. Cell numbers were reduced from the initial seeding density by one log each week until reaching a density of 10(2) cells. These cells were found to be stable in viability and cytotoxic activity, after which limiting dilution was then performed. Within 4 to 6 wk, clones were isolated with unique specificities. These clones were capable of proliferating to a total density of 10(9) cells/ml and maintained their specific cytotoxicity for more than 6 mo. Testing with a panel of target cells of various histotypes, cold-target inhibition assays, and blocking of cytotoxicity with anti-HLA monoclonal antibodies showed that the T cell clones recognize a common sarcoma-associated antigen and that the lysis is HLA restricted. Phenotypically, cytotoxic clones derived from JM were Leu-1+, Leu 2+, and Leu-3-, whereas those derived from EG exhibited either Leu-24 or Leu-3+ markers, the latter phenotype lacking cytotoxicity. RM exhibited mainly Leu-3+ clones with strong cytotoxicity. All were HNK-1- and HLA class II+, with less than 1% of cells of each clone stained by anti-TAC monoclonal antibody. The clones from each patient did not lyse autologous or allogeneic PBL, mitogen induced T lymphoblasts, normal fibroblasts, cells isolated from benign neoplasms, carcinoma cells, Daudi B lymphoid cells, or K562 cells. With the exception of EG, all clones produced immune interferon in a range from 12 to 50 U/ml. The generation of long-term specific T cell clones can be used to further dissect the cellular immune response to sarcomas. Cytotoxic T cell clones have potential application for tumor immunotherapy. PMID- 3093590 TI - A rare case of meningitis due to Neisseria meningitidis group 29E. AB - We report a case of meningitis due to Neisseria meningitidis group 29E. The organism was serum-sensitive and therefore not expected to be encountered in an immunologically competent young man. Trauma sustained in a road traffic accident 18 months earlier had affected the tympanic membrane and middle ear, allowing direct infection of the meninges. Myringoplasty was performed to prevent recurrent infection. PMID- 3093589 TI - Ceftazidime alone for treating Pseudomonas aeruginosa septicaemia in neutropenic patients. AB - Twenty-nine patients with primary or secondary hypoplastic bone-marrow were treated successfully with ceftazidime alone for established septicaemia caused by Pseudomonas aeruginosa of which 38% strains were gentamicin-resistant . All the patients were neutropenic at the start of therapy; most were cured with microbiological confirmation before the bone marrow had regenerated. One patient died of cerebral haemorrhage due to profound thrombocytopenia without evidence of infection at autopsy. Significant toxicity was not observed. Ceftazidime alone is, therefore, a safe and effective treatment for infections caused by this organism even in the neutropenic patient. PMID- 3093591 TI - Carriage of Listeria monocytogenes and related species in pregnant and non pregnant women in Aberdeen, Scotland. AB - The faecal, cervico-vaginal and oropharyngeal carriage of Listeria species in 54 healthy pregnant women and 60 healthy non-pregnant women was investigated. Samples were cold-enriched at 4 degrees C and subcultured on selective media containing acriflavin, nalidixic acid and potassium thiocyanate. Listeria monocytogenes was isolated from the faeces of one pregnant woman (2%) and two non pregnant women (3.4%). Listeria innocua was isolated from the faeces of one pregnant woman (2%) and one non-pregnant woman (1.7%). Listeria seeligeri was isolated from the faeces of one non-pregnant woman (1.7%). Listeria species were not isolated from cervico-vaginal or oropharyngeal samples. The results indicate that pregnancy does not affect the naturally low carriage rate of Listeria species. PMID- 3093592 TI - Dermis-derived 15-hydroxy-eicosatetraenoic acid inhibits epidermal 12 lipoxygenase activity. AB - The purpose of the present study was to analyze the metabolism of arachidonic acid (AA) in normal human dermis. After incubating homogenized dermis with exogenous AA, the extracted lipids were isolated by reversed-phase high performance liquid chromatography. Each chromatographic peak was characterized by its UV absorption spectrum and identified by its coelution with the appropriate authentic standard and by radioimmunoassay of its eluate fraction. Identified compounds were quantitated by integrated optical density. Homogenized human dermis transformed AA into both cyclooxygenase and lipoxygenase products, but predominantly 15-hydroxy-eicosatetraenoic acid (15-HETE). Cultured fibroblasts from normal human dermis also mainly metabolized AA into 15-HETE. To determine whether dermis-derived 15-HETE might modify the AA metabolism of epidermis, normal human epidermis was incubated with dermis. Increasing amounts of dermis resulted in an increasing inhibition of epidermal 12-HETE formation. Similarly, 15-HETE alone induced a dose-dependent decrease of epidermal 12-HETE formation, while the formation of prostaglandin E2 was unchanged. Since 12-HETE possess the ability to elicit skin inflammation and to stimulate epidermal DNA synthesis, 15 HETE formation may be a way whereby dermis regulates important epidermal activities. PMID- 3093593 TI - Monoclonal antibody labeling of mononuclear cell surface antigens in formaldehyde fixed paraffin-embedded cutaneous tissue. AB - The influence of the sequential stages of conventional formaldehyde fixation and paraffin embedding of cutaneous tissue on monoclonal antibody labeling of cell surface antigens is described. The effects of variation in fixation time, dehydration, clearing, wax embedding, and enzyme treatment of cutaneous sections were examined. By curtailing fixation time, using cold ethanol dehydration, and limited cold clearing with xylene, immunoreactivity of several important monoclonal antibodies was retained. Wax embedding could be achieved at 58 degrees C for 1 h or by using low-melting-point wax at 42 degrees C for 3 h. Thus was derived an optimal processing procedure which afforded good tissue morphology and allowed reliable reproducible labeling by monoclonal antibodies to cell surface antigens. PMID- 3093594 TI - Immunohistologic studies of squamous cell carcinoma: possible participation of Leu-7+ (natural killer) cells as antitumor effector cells. AB - Immunohistologic studies of 8 patients with squamous cell carcinoma (SCC) were undertaken using a series of monoclonal antibodies. In all of the patients, over 70% of the dermal infiltrates reacted with OKT3 and OKIal (HLA-DR), with a slight predominance of the OKT8+ suppressor/cytotoxic T subset (the mean OKT4/OKT8 ratio was 0.85). Both OKT4+ and OKT8+ subsets could be seen in contact with individual cancer cells. The percentage of OKB7+ (B) cells was less than 29% of the dermal infiltrates. Some Leu-7+ cells (less than 9% of the infiltrates) were seen in close association with individual cancer cells and none of these cells was present apart from the cancer cells. Few OKT6+ cells were observed in the papillary dermis and these had no relation to cancer cells. In the epidermis, OKT6+ dendritic cells remained within normal proportions. Staining with OKM1 revealed sporadic reactive cells. These results strongly suggest that besides T and B lymphocytes, Leu-7+ (natural killer) cells participate in a significant defense mechanism against SCC proliferation. PMID- 3093595 TI - Serum-mediated inhibition of the interferon-gamma-induced HLA-DR expression on monocytes in patients with psoriasis. AB - Psoriatic patients have a decreased proportion of monocytes expressing class II major histocompatibility complex antigens (DR+ monocytes) in their peripheral blood. The expression of the DR antigen on monocytes after culture in the presence of either autologous lymphocytes (endogenous interferon-gamma, IFN gamma) or exogenous IFN-gamma was investigated. In normal AB serum the lymphocytes of the majority of the patients showed a spontaneous IFN-gamma production which was sufficient for DR antigen induction, while the monocytes displayed approximate normal susceptibility to exogenous IFN-gamma as judged by DR antigen expression. However, the sera of psoriatic patients contained one or more factors that interfered with the IFN-gamma-mediated DR antigen expression on cultured monocytes of the same patients. Restoration of IFN-gamma-induced DR antigen expression on monocytes in the presence of the patient's sera was achieved by the addition of superoxide dismutase, 2-mercaptoethanol, or indomethacin. The clinical significance of these observations is discussed. PMID- 3093596 TI - [Long-term vasodilator therapy of chronic refractory heart failure in patients with dilated cardiomyopathy]. AB - The effect of long-term vasodilator therapy (hydralazine, ecarazine or budralazine + isosorbide dinitrate) were evaluated for 20 patients with chronic congestive heart failure due to dilated cardiomyopathy (DCM) resistant to conventional therapy. There were 16 men and four women whose ages ranged from 30 to 74 years (mean 52 years). Fifteen patients were in NYHA class III, and five in class IV. All patients continued their previous therapeutic regimens during this study. Hemodynamic measurements were performed with a triple lumen flow-directed balloon-tipped catheter for 15 patients to evaluate the effects of vasodilator therapy. In the other five patients, heart rate, blood pressure, chest radiography for heart size (CTR) and M-mode echocardiography were monitored. The hemodynamic responses to the combined vasodilator therapy for 15 patients showed significant decreases in afterload and preload concomitant with an increase in cardiac output. The noninvasive evaluations of combined vasodilator therapy in five patients resulted in significant improvement in heart size and ejection fraction. In all 20 patients, symptoms were significantly improved. Side effects and drug toxicity were uncommon during vasodilator therapy. It is concluded that combined vasodilator treatment is the most ajunctive therapy for the management of severe refractory heart failure due to DCM. In addition, long-term nonparenteral vasodilators can be administered even in an outpatient clinic without hemodynamic monitoring. PMID- 3093597 TI - [An analysis of 147 patients with septicemia at the Department of Internal Medicine of Yamaguchi Prefectural Central Hospital during 16 years (1968-1983). I. Clinical observations]. PMID- 3093598 TI - [An analysis of 147 patients with septicemia at the Department of Internal Medicine of Yamaguchi Prefectural Central Hospital during 16 years (1968-1983). II. Analysis of factors which deteriorated the prognosis of septicemia and therapeutic considerations]. PMID- 3093599 TI - [Evaluation of sero-diagnostic technics in the diagnosis of Chlamydia psittaci infection, a study on experimental infection]. PMID- 3093600 TI - [Enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to Legionella pneumophila]. PMID- 3093601 TI - [Epidemiologic and virologic studies on outbreaks of nonbacterial acute gastroenteritis associated with oysters in Tokyo]. PMID- 3093602 TI - [Seroepidemiologic study of hepatitis B virus infection in merchant marine college students]. PMID- 3093603 TI - [Study on avian chlamydiosis. Part III. Chlamydial isolation from the feces of feral pigeons]. PMID- 3093604 TI - [Effect against macrophages of purified SPA of S. enteritidis]. PMID- 3093605 TI - [Clinical study of AM-715 on acute infectious enteritis. The Japan Research Committee of AM-715, Research Group for Acute Infectious Enteritis]. PMID- 3093606 TI - [A case of sino-broncho-bronchiolitis with persistent infection of the lower airway due to Klebsiella pneumoniae]. PMID- 3093607 TI - Characterization of Listeria monocytogenes-induced murine natural killer cells. PMID- 3093608 TI - Activated macrophages as effector cells of protective immunity to schistosomiasis. PMID- 3093609 TI - Regulation and role of thyroid cell class II antigen expression. PMID- 3093610 TI - Analysis of the function of L3T4+ T cells by in vivo treatment with monoclonal antibody to L3T4. AB - We have used MAb to L3T4 to examine the function of L3T4+ T cells in normal and autoimmune mice. Treatment of mice with MAb to L3T4 profoundly depleted L3T4+ cells from the blood, spleen, and lymph nodes, but not the thymus. In BALB/c and C57BL/6 mice, selective depletion of L3T4+ cells blocked both primary and secondary humoral immune responses and inhibited, but did not prevent, cellular immune responses. In lupus-prone B/W and BXSB mice, depletion of L3T4+ cells significantly retarded autoimmune disease. Because the L3T4 antigen in mice is homologous to the CD4 antigen in humans, these findings have implications regarding the function of CD4+ T cells and the prospects for using MAb to CD4 as therapeutic agents. PMID- 3093611 TI - [The antitumor efficacy of lymphokine-activated killer (LAK) cells and gamma interferon production induced in vitro from peripheral blood lymphocytes of patients with malignant gliomas]. PMID- 3093612 TI - [Influence of OK-432 on the concentration of active substance of fluoropyrimidine carcinostatics in the living body]. PMID- 3093613 TI - [The effects of estradiol and prolactin on DMBA-induced mammary tumor in rats]. PMID- 3093615 TI - Ultrastructure of the human preovulatory oocyte. AB - The ultrastructure of preovulatory human oocyte-cumulus complexes was described after inducing maturation by clomiphene, human menopausal gonadotropin (hMG), human chorionic gonadotropin (hCG) treatment. The majority of the oocytes was at metaphase II of meiosis, with a radially orientated spindle. The oocyte surface was covered by a multitude of microvilli. Cortical granules were nonuniformly distributed along the cortex. A cytoplasmic polarization was observed. The cytoplasmic organelles were in general uniformly dispersed, with the exception of a narrow segment within which cytoplasmic membranes and mitochondria formed clusters. The spindle was usually found at the borderline between the two regions of the cytoplasm. The functional significance of this polarization is not yet known. PMID- 3093614 TI - Oocyte maturation inhibitor activity in human follicular fluid: quantitative determination in unstimulated and clomiphene citrate- and human menopausal gonadotropin-stimulated ovarian cycles. AB - Since removal of the oocyte from the intrafollicular milieu allows meiotic resumption and germinal vesical breakdown to proceed, the concept of an intrafollicular oocyte maturation inhibitor (OMI) has evolved. Accordingly, we asked the following questions: Is there OMI activity in human follicular fluid? Does OMI activity change with ovarian hyperstimulation? and Does OMI activity correlate with oocyte fertilization or the concentration of steroids in the corresponding follicular fluid? Fresh cumulus enclosed porcine oocytes from small follicles were incubated with human follicular fluid aspirates from normally menstruating patients with or without treatment: unstimulated follicles (N = 10), clomiphene citrate (150 mg/day) (N = 10)-treated cycles, and human menopausal gonadotropin (hMG) (N = 12)-treated cycles. A lyophylized porcine follicular fluid standard and serum-free culture media were used as positive and negative controls, respectively. After a 40-hr incubation with test materials, the oocytes were fixed, stained, and evaluated for oocyte maturation as determined by germinal vesical breakdown. Human follicular fluid, estradiol, progesterone, androstenedione, and testosterone levels were determined by radioimmunoassay. The 50% inhibitory dose (ID50) for OMI activity in follicular fluid from untreated, spontaneously menstruating women was less than that for follicular fluid from clomiphene-stimulated patients, which was less than that for follicular fluid from hMG-stimulated patients. The difference between OMI values from untreated and hMG-stimulated follicular fluids was statistically significant. Human oocytes removed from follicular fluid with higher OMI activity tended not to fertilize in vitro compared to the relatively lower OMI activity present in follicular fluid yielding oocytes which did fertilize.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093616 TI - Pregnancy after in vitro fertilization, cryopreservation, and embryo transfer. AB - We reported on the first pregnancy achieved in the Erlangen IVF program after cryopreservation and embryo transfer. After hMG stimulation in the first treatment cycle, nine oocytes were retrieved by laparoscopy from a 31-year-old woman and three embryos transferred. Five other oocytes were fertilized and developed to four- to eight-cell embryos, which were subsequently cryopreserved. Transfer of these embryos two cycles later resulted in a singleton pregnancy and the birth of a healthy girl. PMID- 3093617 TI - Urinary excretion and renal production of prostaglandins E2, F2 alpha, and thromboxane B2 in experimental diabetes mellitus. AB - To delineate the urinary excretion of prostaglandins E2 (PGE), F2 alpha (PGF), and thromboxane B2 (TxB) in diabetic rats, we treated male Sprague-Dawley rats with streptozocin 60 mg/kg or with vehicle. Plasma glucose and creatinine concentration and 24-hour urine collections for determination of TxB, PGE, PGF, creatinine, and protein excretion were measured at 2, 8, and 14 weeks after streptozocin. Creatinine clearance was significantly decreased in diabetic rats at 2 and 8 weeks, whereas the urinary protein excretion was three to five times that of control animals at all times. The 24-hour excretion of TxB was elevated twofold to threefold in diabetic rats, whereas PGE and PGF excretion were both significantly decreased. This alteration in excretion was not caused by increased urine flow rate, inasmuch as mannitol-induced osmotic diuresis caused an increase in PGE and PGF excretion. Eight weeks after streptozocin, a group of diabetic and control rats were sacrificed, and the production of PGE, PGF, and TxB by the renal papillae and glomeruli determined. An additional five diabetic rats were treated with protamine zinc insulin for 1 week before sacrifice to determine the effect of insulin treatment on the production of PGE, PGF, and TxB by the glomeruli and renal papillae. Papillary production of PGE, PGF, and TxB was decreased in diabetic rats, as was glomerular production of PGE and PGF. Insulin treatment increased PGF production by the renal papillae and increased PGE, PGF, and TxB production by glomeruli. These results indicate that changes in prostaglandin excretion accompany the development of marked proteinuria and a decrease in creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093618 TI - Lysosomal hydrolases in blood-derived macrophages of patients with I-cell disease. AB - Three lysosomal hydrolases, beta-galactosidase, beta-glucuronidase, and beta-N acetylglucosaminidase, were examined in blood-derived macrophages and media of two patients with I-cell disease. The activities of the three enzymes were lower in I-cell macrophages than in normal controls. However, the media collected from these cells possessed higher activities than control media. beta-N acetylglucosaminidase derived from media of I-cell macrophages was not endocytosed by fibroblasts from patients with Sandhoff's disease and was only partially endocytosed by I-cell macrophages. These findings indicate that blood derived macrophages of patients with I-cell disease are affected. In addition, the data presented suggest the presence of two types of receptors in human blood derived macrophages: mannose and mannose-6-phosphate. PMID- 3093620 TI - Enzymology of long-chain base synthesis by aorta: induction of serine palmitoyltransferase activity in rabbit aorta during atherogenesis. AB - Serine palmitoyltransferase [EC 2.3.1.50] initiates the biosynthesis of sphingolipids by catalyzing the condensation of a fatty acyl-CoA with serine to yield the committed intermediate 3-ketosphinganine or one of its homologues. The presence of serine palmitoyltransferase in aorta was established under optimal assay conditions using microsomes from New Zealand White rabbits. Its activity was dependent on microsomal protein, L-serine, pyridoxal 5'-phosphate, and palmitoyl-CoA. Although several different saturated and unsaturated fatty acyl CoA thioesters were utilized as substrates, maximal activity was with palmitoyl CoA, suggesting that this enzyme contributes to the predominance of 18-carbon long-chain bases in sphingolipids from aorta. Rabbits, fed a Purina lab chow supplemented with 2% cholesterol, were used to study serine palmitoyltransferase activity in aorta during experimental atherogenesis. An increase in activity from intimal-medial preparations was detectable prior to prominent lipid accumulation or cellular proliferation. Activity continued to elevate over the 12-week duration of feeding concurrent with the increase in serum cholesterol and in proportion to the development of plaques resulting in a 3.7-fold increase in activity (20.7 +/- 2.6 pmol per min per mg microsomal protein +/- SE in the cholesterol-fed group versus 5.6 +/- 1.9 in the pair-fed controls also matched for age and sex; P less than 0.005). Thus, the accumulation of sphingomyelin that occurs in aorta during experimental atherogenesis may be related to increased long-chain base synthesis by serine palmitoyltransferase. PMID- 3093619 TI - Amino acid sequence of rat apolipoprotein A-II deduced from the nucleotide sequence of cloned cDNA. AB - A rat apolipoprotein A-II cDNA clone was isolated from a rat liver cDNA library by in situ hybridization of bacteriophage plaques using a 32P-labeled human apoA II cDNA as a probe. The cDNA insert from this clone was characterized by DNA sequencing. The amino acid composition derived from the DNA sequence data matched well with that of rat apoA-II reported earlier (Herbert et al. 1974. J. Biol Chem. 249: 5718-5724), indicating that the cDNA insert coded for rat apoA-II. Further evidence was provided by a comparison of the amino acid sequence of rat apoA-II obtained here with that of human apoA-II (Brewer et al. 1972. Proc. Natl. Acad. Sci. USA. 69: 1304-1308). While the rat apoA-II cDNA insert did not code for the entire presegment, it had the same COOH-terminal residues of the presegment as well as the same prosegment (Ala-Leu-Val-Arg-Arg) as in human preproapoA-II, suggesting that rat apoA-II was also synthesized initially as preproapoA-II. Mature rat apoA-II contains 79 amino acids. Residue 6 of mature rat apoA-II is Asp, while it is Cys in human apoA-II, and this would account for the absence of dimeric forms of rat apoA-II in plasma. While the overall amino acid sequence homology between rat and human apoA-II is about 50%, the amphipathic alpha-helical structures, which are responsible for lipid-binding, seem to be conserved in the two proteins. The size of rat apoA-II mRNA was estimated to be about 600 nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093621 TI - Intraoperative radiation therapy. PMID- 3093622 TI - Effects of therapeutic dosage of gamma ray on the drug susceptibility of mycobacteria. PMID- 3093623 TI - Microheterogeneity of anterior pituitary FSH in the male rat: isoelectric focusing pattern throughout sexual maturation. AB - Anterior pituitary glands were removed from male rats at 5, 10, 15, 18, 21, 28, 30, 40, 50 and 90 days of age, and the multiple forms of FSH present within them were separated by polyacrylamide gel-isoelectric focusing (PAGE-IEF; pH range 3.0 8.0). Gel eluents were analysed for FSH content by radioimmunoassay (RIA) and a specific radioreceptor assay (RRA). All pituitaries studied exhibited one or more peaks of immunoactive FSH within a pH range of 7.0-3.0; the major peak exhibited an isoelectric point (pI) of 4.9-4.0. Between 25 and 56% of anterior pituitary FSH obtained from rats 5-30 days old focused within a pH range of 4.9-4.5, whilst in older animals (greater than or equal to 40 days) this pH range contained 17 27% of the total FSH recovered. In contrast, in animals 40-90 days old, the greatest proportion of immunoactive FSH (42-62% of the total immunoactivity recovered) focused within a pH range of 4.4-4.0; further, only these groups of animals exhibited a significant proportion of anterior pituitary FSH with a pI less than or equal to 3.9. Between 14 and 21% of total FSH from 5- to 30-day-old rats focused within a pH range of 5.4-5.0, whereas in older animals this pH range contained 6-9% of the total FSH recovered. These shifts in FSH pI occurred at the time of appearance of spermiogenesis, at 45 days of age. Although the ratio of the concentration of FSH measured by RRA to that measured by RIA declined as the pI of the anterior pituitary FSH decreased throughout a pH range of 7.0-4.0, the most acidic FSH molecules (pI less than 4.0) showed an abrupt increase in that ratio. These results demonstrate that the transition from sexual immaturity to adulthood is accompanied by qualitative changes of intracellular pituitary FSH. They contrast with previous findings in female rats in which a shift to less acidic anterior pituitary FSH forms was detected at the time of vaginal opening, thus indicating the existence of a sexual dichotomy in terms of the action of gonadal steroids on the type of FSH molecule synthesized by the anterior pituitary gland. PMID- 3093624 TI - The acid-base status of prenatal pups of the dogfish, Squalus acanthias, in the uterine environment. AB - The acid-base status of late-term Squalus acanthias L. pups in the uterine seawater environment was examined. Blood values for pH, total CO2, partial pressure of CO2, urea and sodium concentrations in late-term pups were not significantly different from those of the mothers. Haematocrit was slightly lower, while total plasma lipid and ammonia concentrations were several times higher. The uterine environment in which these pups reside and maintain normal acid-base status is nevertheless quite remarkable. In the later months of gestation, up to six pups (approx. 60 g each) reside in each horn of the uterus, in about 100 ml of seawater, in which they ventilate. While the major ion concentrations of the uterine fluid resemble normal seawater, the pH may be as low as 5.9, and the ammonia concentration as high as 22 mmol l-1. This system provides a unique opportunity to study acid-base balance, respiration and nitrogenous waste excretion in developing elasmobranchs under quite unusual conditions. PMID- 3093625 TI - Recombinant gamma interferon induces hypertriglyceridemia and inhibits post heparin lipase activity in cancer patients. AB - Animals suffering from malignancy or chronic infection develop characteristic metabolic abnormalities, including a well-defined hypertriglyceridemic state. These abnormalities have been attributed to release of one or more mediators from activated macrophages. We report that cancer patients receiving RIFN-gamma, a potent macrophage activator, at doses of greater than or equal to 0.25 mg/m2/d i.m. show marked increases in triglyceride but not in cholesterol levels (pretreatment triglyceride level of 180 +/- 190 mg/dl [mean +/- SD] vs. a day-14 level of 370 +/- 242 mg/dl, n = 23, p less than 0.001 by the paired t test). This hypertriglyceridemia was characterized by an increase in very low-density lipoproteins and a decrease in plasma post-heparin lipase activity, consistent with defective triglyceride clearance (mean pretreatment lipase level of 2.1 mumol/ml/h vs. a day-14 level of 1.2 mumol/ml/h, n = 6, p = 0.02 by the paired t test). rIFN-gamma did not directly inhibit lipoprotein lipase enzymatic activity in vitro. Other possible mechanisms of action, such as suppression of lipase by an rIFN-gamma-induced mediator released from activated macrophages, or a direct effect of interferon on lipase biosynthesis, require further investigation. Our observations provide evidence that factors produced by the immune system can regulate lipid metabolism in man. PMID- 3093626 TI - Lymphokine-activated killer cells. Analysis of progenitors and effectors. AB - IL-2 has been examined for its ability to regulate lymphokine-activated killer (LAK) activity. IL-2 is a potent activator of cytolytic activity against a wide array of tumor cells, including those from fresh autologous and allogeneic tumors. Using subpopulations of lymphoid cells that were separated on Percoll density gradients, and subsequently purified by immunoadsorbance, studies were performed to examine the phenotypes of progenitor and effector cells of human LAK cells and to compare them with the phenotype of activated NK cells. From these studies, it was evident that several lymphoid subsets, including CD3+, CDw16- and CD3-, CDw16+ cells could mediate LAK lysis of fresh tumor cells. Our examination of the kinetics of activation revealed that CDw16+, NKH1+ (NK-active) cells were maximally activated by 1-2 d. In contrast, CD3+ cells appeared not to achieve maximal cytolytic activity against fresh and cultured tumor cells until days 2-3. Using limiting-dilution frequency analysis, we showed that a large percentage of cytolytically active progenitors was present among the CDw16+, NKH1+ cells. The progenitor and effector cell frequencies appear to be 10-50 times higher in these populations compared to CD3+ cells. In addition, the selective blockage by mAb to the CD3 determinant of the T cell receptor complex indicated that these two effector cell phenotypes relied on different receptors to mediate their cytotoxic activity against tumor cells. Therefore, the accumulated data suggest that there is not a single unique progenitor of LAK activity, but rather that multiple subsets of lymphocytes become cytotoxic in response to IL-2. However, the NK cell population forms the largest single component of LAK cell activity in human peripheral blood. PMID- 3093629 TI - Enzymic clearing of lipaemic serum following total parenteral nutrition: determination of neonatal bilirubin as a model. AB - Bilirubin determinations in the newborn infant are one of the many analytical tests that can yield misleading results when the specimen is either iatrogenically or naturally lipaemic. Incorporation of a recently reported enzymic clarification system into a commercially available test kit enables one to conveniently and accurately quantify both total and direct bilirubin within the present procedural characteristics of the Bilirubin Stat Analyser Photometer. This instrument measures the former directly with bichromatic spectrophotometry and the latter with a conventional diazo-type reaction. The proposed modification of existing reagents allows one to apply the assay to samples with as much as, and possibly more than 16 g/l of triglycerides which has been introduced into the vascular circulation as intravenous total parenteral nutrition. PMID- 3093628 TI - VH gene expression is restricted in anti-IgG antibodies from MRL autoimmune mice. AB - Antibodies directed against IgG and DNA are found in the sera of autoimmune MRL/Mp lpr/lpr mice. Little is known of the molecular mechanisms underlying expression of such autoantibodies. We have investigated the binding diversity and pattern of VH gene expression in a panel of murine anti-IgG antibodies. We constructed eight hybridoma clones secreting IgM antibodies that bound to mouse IgG by using spleen cells from MRL/Mp lpr/lpr mice varying in age from 4 to 15 wk; one clone was derived from a 32-wk-old MRL +/+ mouse. The monoclonal IgM products exhibited varying binding specificities for intact mouse IgG, fragments of mouse IgG [Fc, Fab, (Fab')2], and heterologous IgG. Two of these antibodies crossreacted with B and/or Z DNA. Probes from seven of eight identified mouse VH gene families (7183, S107, Q52, J558, J606, 36-60, and 3609) were hybridized under high-stringency conditions with cytoplasmic RNA blots from each clone. Six clones hybridized only with the probe from the five-member 36-60 family. The remaining three clones crosshybridized with the 36-60 probe and the probe from the 60 member J558 family, perhaps reflecting somatic mutation from the original germline VH gene resulting in recognition by a probe from another family, in addition to the probe from the original germline family. Our results indicate that spontaneous MRL lpr/lpr anti-IgG antibodies are encoded predominantly by the 36-60 VH gene family and imply a nonrandom selection of this VH gene family in the production of these antibodies. PMID- 3093627 TI - Tumor necrosis factor and lymphotoxin induce differentiation of human myeloid cell lines in synergy with immune interferon. AB - We show that the cytotoxins tumor necrosis factor (TNF) or lymphotoxin (LT), at concentrations of approximately 10(-11) M induce monocytic differentiation of human myeloid cell lines. After 5 d of culture in the presence of rTNF and LT, a significant proportion of the myeloid cell lines express monocyte differentiation antigens and ANAE activity, and become able to reduce nitroblue tetrazolium (NBT) and mediate low levels of ADCC against tumor target cells. These markers of differentiation, however, are maximally induced when rIFN-gamma, at concentrations as low as 4 U/ml, is present simultaneously with the cytotoxins, and the two classes of cytokines act synergistically to induce terminal differentiation. The appearance of monocytic antigens is accompanied by acquisition of morphology and other functional properties of mature monocytic cells, such as chemiluminescence and phagocytosis, and by expression of FcR for monomeric IgG. A decrease in cell proliferation accompanies induced differentiation, and is not due to the cytotoxic properties of TNF or LT, as indicated in simultaneous analysis of surface phenotype and cell cycle. The lack of cytotoxicity of TNF on the HL-60 cell line is also demonstrated by the enhancing effect of TNF on HL-60 cell growth and nucleoside uptake in the first 2 d of culture. These data show that the cytotoxins TNF and LT mediate complex effects on cells of the myelomonocytic lineage and, in synergy with IFN-gamma, can fully induce immature myeloid cells to differentiate into cells with phenotypic, functional, and proliferative characteristics of terminally differentiated myelomonocytic cells. PMID- 3093630 TI - Distribution of interstitial retinol-binding protein (IRBP) in the vertebrates. AB - Immunoblots of interphotoreceptor matrix preparations from 20 species belonging to six vertebrate classes were probed with antibodies against bovine interstitial retinol-binding protein (b-IRBP). Each preparation displayed an immunoreactive protein band. In the Osteichthyes, the apparent Mr of this band was 67,600 +/- 2,700 (mean +/- SD, n = 8). In two of the Osteichthyes, the band was resolved into a closely spaced doublet. Including previously published data for five mammals and one amphibian, species from the other classes (Chondrichthyes, one species; Amphibia, four species; Reptilia, one species; Aves, one species; Mammalia, nine species) had IRBPs with Mr that averaged 2.0 times that of the Osteichthyes, namely 134,200 +/- 8,600 (mean +/- SD, n = 17). Frog IRBP was very similar to mammalian IRBP in terms of its immunohistochemical distribution (determined with rabbit anti-frog IRBP antibodies), its molecular weight (sodium dodecyl sulfate polyacrylamide gel electrophoresis and gel-filtration chromatography), retinol- and concanavalin A-binding ability, and because it was synthesized and secreted in vitro by the isolated retina but not by the pigmented layers of eye. Goldfish IRBP apparently binds exogenous (3H)-retinol but does not bind concanavalin A and has about half the Mr of frog IRBP. The occurrence of IRBP-like proteins cross-reacting with anti b-IRBP antibodies in the interphotoreceptor matrix of all six major vertebrate classes is consistent with the hypothesis that IRBP is an important element in the vertebrate visual cycle. PMID- 3093631 TI - Dependence of GnRH action on Na+, K+, and Ca2+ in the frog, Rana pipiens, pituitary. AB - The roles of K+, Ca2+, and Na+ ions in the mechanism of gonadotropin releasing hormone (GnRH) action on frog (Rana pipiens) hemipituitaries were studied using an in vitro superfusion system. The effects of elevated K+ alone or in combination with Ca2+-depleted medium, tetrodotoxin (TTX), or with 100 ng/ml GnRH were examined. The involvement of K+ was also studied indirectly through the use of tetraethyl ammonium chloride (TEA). The importance of Ca2+ was established by the loss of responsiveness to GnRH in Ca2+-depleted medium, or in the presence of the Ca2+ competitor CoCl2. The absence of a major dependence of GnRH on Na+ was revealed by the continued gonadotropin secretion after addition of 1 microM TTX to medium containing GnRH or 36.3 mM KCl, or by replacement of NaCL with choline chloride. High (10 X normal) KCl (36.3 mM) stimulated gonadotropin--both LH and FSH--secretion, but the response was more gradual than for GnRH. The inclusion of TEA (to block K+ efflux) in medium with GnRH accentuated the effect of GnRH, and the effects of elevated (36.3 mM) KCl and 100 ng/ml GnRH (a relatively high dose) were additive. Responses to high K+, like GnRH, were abolished by removal of Ca2+ from the medium. Overall, the roles of K+, Ca2+, and Na+ ions in the mechanism of GnRH action are very similar between mammals and frogs; Ca2+ apparently serves a critical function in the mechanism of GnRH action, while Na+ appears not to be involved. K+ can induce gonadotropin secretion, but it is not clear that it plays a direct role in the mediation of the action of GnRH. PMID- 3093632 TI - Appraisal of glibenclamide administration before, with, or after the meal. PMID- 3093633 TI - Monoclonal antibodies to cell surface antigens involved in sex pheromone induced mating in Streptococcus faecalis. AB - Hybridoma cell lines producing monoclonal antibodies to Streptococcus faecalis cell surface antigens were constructed. Some of the antibodies isolated were directed against surface components involved in pheromone-induced mating. This paper describes the use of the monoclonal antibodies to identify antigenically related surface components detected by immunoprecipitation and Western blotting, their use in pheromone response assays, and their use as functional inhibitors in mating experiments. PMID- 3093634 TI - Differential scanning calorimetry of bacteria. AB - Thermograms obtained by differential scanning calorimetry of a range of bacteria of different heat resistances were compared. Equations were derived to calculate the rate at which the numbers of viable organisms in a calorimeter decline as the temperature is raised at a constant rate. Vegetative bacteria scanned at 10 degrees C min-1 showed multi-peaked thermograms with four major peaks (denoted m, n, p and q) occurring in the regions 68-73, 77-84, 89-99 and 105-110 degrees C respectively. Exceptions were that peak m (the largest peak) occurred at 79-82 degrees C in Bacillus stearothermophilus and an additional peak, r, was detected in Escherichia coli at 119 degrees C. At temperatures below the main peak m there were major differences in thermograms between species. There was a direct relationship between the onset of thermal denaturation and the thermoresistance of different organisms. Heat-sensitive organisms displayed thermogram features which were absent in the more heat-resistant types. When samples were cooled to 5 degrees C and re-heated, a small endothermic peak, pr, was observed at the same temperature as p. Peaks p and pr were identified as the melting endotherms of DNA. In all vegetative organisms examined, maximum death rates, computed from published D and z values, occurred at temperatures above the onset of thermal denaturation, i.e. cell death and irreversible denaturation of cell components occurred within the same temperature range. PMID- 3093635 TI - Preliminary characterisation of torovirus-like particles of humans: comparison with Berne virus of horses and Breda virus of calves. AB - Pleomorphic virus-like particles have been observed by electron microscopy in the faeces of children and adults with diarrhoea. Some of these particles were approximately 100 nm in diameter and had a "fringe" of closely applied peplomers approximately 10 nm long; they closely resembled Berne virus of horses and Breda virus of calves, the two representatives of a newly proposed family called the Toroviridae. In one sample a toroidal nucleoprotein-like structure was observed within the particles. For two samples a buoyant density of 1.14 g/ml was determined by centrifugation through a sucrose density gradient. One sample possessed a haemagglutinin for rat erythrocytes. The serological relationship between these different viruses was observed by immune electron microscopy, haemagglutination inhibition, and serum neutralisation. The role of these virus like particles as candidate pathogens of humans is discussed. PMID- 3093636 TI - UDPgalactose:ceramide galactosyltransferase of rat brain: a new method of purification and production of specific antibodies. AB - A new method for purification of UDPgalactose:ceramide galactosyltransferase (EC 2.4.1.45) is described. The principal steps involved solvent extraction at -70 degrees C, Triton X-100 extraction, and DEAE-Sephadex and Blue Sepharose chromatography. The active configuration of the enzyme was stabilized by phospholipids and a rapid loss of enzymatic activity was observed after removal of these lipids. The inactive enzyme could be fully reactivated in the presence of brain phospholipids dispersed in a Triton X-100-containing buffer. The purified enzyme preparation showed two major components by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate with apparent molecular weights of 50-70,000. The 53,000-dalton protein was isolated by preparative gel electrophoresis in the presence of sodium dodecyl sulfate and used to produce antibodies against UDPgalactose:ceramide galactosyltransferase. PMID- 3093638 TI - Microheterogeneity of microtubule-associated tau proteins is due to differences in phosphorylation. AB - We have studied the heterogeneity of the microtubule-associated tau proteins using tau-specific antibodies and two-dimensional electrophoresis. Both monoclonal and polyclonal antibodies to tau proteins recognize five bands in cow brain microtubule proteins run on sodium dodecyl sulfate (SDS)-polyacrylamide gels, with apparent molecular weights between 56,000 and 66,000. Immunoblots of cow brain microtubules separated on two-dimensional gels, using nonequilibrium pH gradient electrophoresis in the first dimension and SDS-gel electrophoresis in the second, reveal that greater than 30 isoforms of tau exist. The tau proteins vary in pI from 6.5 to 8.5, with the higher-molecular-weight forms being more acidic. The microheterogeneity of tau is not induced by cycling of microtubules, because two-dimensional immunoblots of tau from total brain are almost identical to those of tau from cycled tubules. Adult rat brain tau, which appears as three doublet bands on SDS gels, also exhibits considerable isoelectric heterogeneity, as does tau from 7-day-old rats, which appears as only one band on SDS gels. After dephosphorylation of cow brain tau with alkaline phosphatase, the highest molecular-weight band disappears on SDS gels. On two-dimensional gels, the number of tau variants decreases by more than half after dephosphorylation, and the more basic species increase greatly in intensity. Preliminary experiments with tau labeled in vivo with 32PO4 also indicate that the more acidic tau proteins are the more highly phosphorylated forms. Thus, isoelectric heterogeneity of tau proteins exists at all ages and is due, at least in part to differences in the state of phosphorylation of tau isoforms. PMID- 3093637 TI - Lesions to the corticostriatal pathways ameliorate hypoglycemia-induced arachidonic acid release. AB - The concentrations of free fatty acids (FFAs) in the neostriatum of control rats and rats subjected to unilateral cortical ablation were measured during and following severe insulin-induced hypoglycemia. The total FFA concentration in the caudate nucleus contralateral to the lesion increased to approximately 1.5 and 3 times the control level after 5 and 30 min of isoelectricity, respectively, and was similar to the control value following 1 h of recovery. After 5 min of isoelectricity, the total FFA pool was significantly smaller in the decorticated striatum. No difference between hemispheres was noted after 30 min of isoelectricity. After 5 min of isoelectricity the levels of stearic and arachidonic acid were selectively increased whereas palmitic acid and oleic acid remained at control levels. In the decorticated striatum of lesioned animals the arachidonic acid concentration was significantly lower, whereas the level of stearic acid was not significantly different from the control value. After 30 min of isoelectricity the levels of all four FFA species were increased. Apart from a significantly lower level of oleic acid on the decorticated side, there were no interhemispheric differences in the FFA levels. Since the early interhemispheric differences in the FFA levels. Since the early interhemispheric hemispheric differences in the levels of arachidonic and stearic acids coincide with a selective decrease in the levels of glutamate and a decreased energy utilization on the decorticated side, the results suggest that glutamate release during hypoglycemia induces an early receptor-mediated degradation of phospholipids, presumably via the phosphatidylinositol cycle. PMID- 3093640 TI - Apnoea testing to confirm brain death in clinical practice. AB - In six patients an apnoea test was carried out to confirm brain death according to a protocol recommended in the USA. After ten minutes' apnoea the pCO2 did not reach the target value of 7.98 kPa (60 mm Hg) in any of these patients. This was caused by the low initial value and the slow increase of the pCO2. Moreover, we could not confirm the belief that the necessary duration of the apnoea test can be predicted by assuming a rise of the pCO2 of 0.33 kPa (2.5 mm Hg) per minute. PMID- 3093641 TI - Concentrations of thyrotropin-releasing hormone in the brain of ataxic mice. AB - Concentrations of thyrotropin-releasing hormone (TRH) were studied in the brain of the Weaver ataxic mouse, the Purkinje cell degenerative ataxic mouse (pcd ataxic mouse) and the cytosine arabinoside (ara-C)-induced ataxic mouse. The brain tissue was dissected into 4 parts, e.g., hypothalamus, cerebrum, cerebellum and brain stem. TRH concentrations in each part of the brain were measured by radioimmunoassay. TRH concentrations in the brain of Weaver ataxic mice were significantly higher in the cerebellum and brain stem than in the controls. In pcd-ataxic mice, the TRH concentrations in the brain were significantly higher in the cerebrum and brain stem. In ara-C-induced ataxic mice, the concentrations were significantly higher in the cerebrum, cerebellum and brain stem. TRH levels in the hypothalamus of ataxic mice did not differ from those of controls. The elution profile of methanol-extracted cerebellum of ataxic mice on Sephadex G-10 was identical to that of synthetic TRH. These findings suggest that changes in the TRH concentrations in the brain play a pathophysiological role in ataxic mice. PMID- 3093639 TI - Acid maltase deficiency: a case study and review of the pathophysiological changes and proposed therapeutic measures. AB - An adult patient with lysosomal acid alpha-glucosidase deficiency was fully investigated, and then placed on various forms of therapy with favourable response to a high protein, low carbohydrate diet. The rationale for the employment of this therapy, the problem of acid maltase deficiency and the relationship to weakness and glycogenosome formation with accumulation or otherwise of glycogen within the muscle fibres is discussed. PMID- 3093642 TI - Polyribosomes associated with synaptic specializations on axon initial segments: localization of protein-synthetic machinery at inhibitory synapses. AB - Previous studies have revealed a selective association between polyribosomes and axospinous synapses in a variety of brain regions. The present study evaluates whether polyribosomes are also associated with the symmetrical and presumably inhibitory synaptic connections found on the initial segment of axons of some neurons in the CNS. The initial segments of pyramidal neurons in the sensorimotor cortex of the monkey and of granule cells in the hippocampus of the rat were examined. The initial segments of these cell types are contacted by GABAergic terminals that form symmetrical synaptic connections. In the present study, these initial segments were found to contain polyribosomes that tended to be selectively localized beneath the synaptic specializations. Both the synaptic connections and the polyribosomes were localized to the initial segment; after the point at which the axon became myelinated, neither synapses nor polyribosomes were found. The association between polyribosomes and synapses was also suggested by the position of the polyribosomes with respect to the synapse. In each cell type, the majority of the polyribosomes that were present in the initial segments appeared to be localized preferentially beneath synaptic sites, although some polyribosomes were also present in the core of the axon. These data reveal that polyribosomes are not peculiar to spine synapses, but rather are ubiquitous components of the subsynaptic region of many types of synapses. We propose that neurons may regulate their innervation by positioning protein-synthetic machinery (and appropriate mRNA molecules) at particular locations in order to construct particular types of synapses at defined positions on the postsynaptic cells' receptive surface. PMID- 3093643 TI - Infinite needs: finite resources. The 1986 Harvey Cushing oration. AB - In this 199th year of constitutional government in the United States a careful evaluation of all our basic institutions is required if this country is to remain a great nation. The delivery of health care, a basic institution, must be included in the determination of how finite resources can be most effectively and efficiently used for what appears to be almost infinite needs. PMID- 3093644 TI - Acuity and staffing under prospective payment. AB - Nursing administrators are debating the desirable mix of professional (RN) and paraprofessional (LPN) nursing staff under the prospective payment system (DRGs). The staffing mix reflects the cost and quality of nursing care provided by an acute care hospital. Based on a reliable and valid acuity/care plan system, standards of care and nursing diagnoses, several DRGs were analyzed on an eight bed medical/surgical intensive care unit with regard to intensity of care and staffing mix. This study showed nursing administrators that the staffing mix on an intensive care unit varies according to the acuity/care plan rather than DRGs or nursing diagnoses. PMID- 3093645 TI - Nursing costs/DRG: a patient classification system and comparative study. AB - This study establishes the actual cost of nursing care for 13 diagnosis related groups (DRGs) at one hospital and relates them, within the limits of available statistics, to other published data. The impact of acuity levels involving both direct and indirect factors in nursing and of "outliers" is emphasized as critical in working within the preset reimbursement schedule of DRGs. More clearly defining these highly variable components of nursing care costs can assist nurse administrators to determine inadequate practice patterns and, by revising them, to decrease costs. PMID- 3093646 TI - Effects of dietary methionine, cystine and potassium sulfate on serum cholesterol and urinary ascorbic acid in rats fed PCB. AB - Liver weight, liver and urinary ascorbic acid levels and serum cholesterol concentration were higher in rats fed polychlorinated biphenyls (PCB) than in controls. The influences of methionine, cystine and potassium sulfate on these metabolic responses were studied. Methionine or equivalent moles of cystine or potassium sulfate were added to a basal diet containing 10% soy protein isolate. The basal diet contained 0.3% of total sulfur-containing amino acids (S-AAs). When methionine was added to the basal diet, maximum gain in body weight was obtained with 0.5% of dietary S-AAs, while the highest values in serum cholesterol and urinary ascorbic acid were obtained with 0.8% of dietary S-AAs in rats fed PCB. Dietary addition of cystine had little effect on body weight gain. Nevertheless, in rat fed PCB, urinary ascorbic acid and serum cholesterol were significantly higher in rats fed the cystine-supplemented diet than in those fed the unsupplemented diet. Addition of potassium sulfate had no effect on body weight gain, urinary ascorbic acid or serum cholesterol. These results suggest that more S-AAs are required for the highest metabolic response to PCB than for maximum growth, and the higher requirement for S-AAs cannot be replaced by inorganic sulfate. PMID- 3093648 TI - Palatinose as a potential parenteral nutrient: its metabolic effects and fate after oral and intravenous administration to dogs. AB - Palatinose (6-O-alpha-D-glucopyranosyl-D-fructose) is a naturally occurring compound which may be valuable as both a sweetener and parenteral nutrient. Its advantage over maltose is that its hydrolysis generates both fructose and glucose. In the present study, conducted with a view to possible clinical use, its metabolic effects and fate after iv injection were investigated. Using dogs as the experimental model, it was found that the behavior of parenterally administered palatinose is in many respects similar to maltose and is likely to be clinically valuable. Importantly, hypertriglyceridemia, a side effect of fructose administration, did not occur, indicating that palatinose may be superior to the use of fructose alone. PMID- 3093647 TI - Selenium-dependent glutathione peroxidase inhibitors increase toxicity of prooxidant compounds in chicks. AB - The acute lethality of paraquat (1, 1'-dimethyl-4,4'-bipyridinium dichloride; also methyl viologen) for chicks was reduced in a dose-dependent manner by adding to a selenium-deficient torula-yeast-based diet low concentrations (0.02-0.04 ppm) of selenium (Se) as either Na2SeO3, selenomethionine or a high Se yeast without significantly increasing plasma Se-dependent glutathione peroxidase (Se GSH-Px) activity. Similarly, chicks orally dosed with 100 mg nitrofurantoin [N-(5 nitro-2 furfurylidine)-1-aminohydantoin] per kilogram had highest mortalities in the Se-deficient (unsupplemented) group; lowest mortalities occurred in chicks supplemented with 0.2 ppm Se; chicks supplemented with 0.02 ppm Se survived at rates not statistically different from chicks either unsupplemented or supplemented with 0.2 ppm Se. The activities of SeGSH-px in various vital organs were significantly elevated by supplementation of 0.2 ppm Se to Se-deficient chicks; but only kidney SeGSH-Px increased with 0.02 ppm Se. Additionally, no histopathology was observed in the vital organs of moribund chicks 5 or 24 h following nitrofurantoin administration at any dietary level of Se tested. Exposure of chicks to oxygen enhanced the toxicity of nitrofurantoin, but the protective effect of dietary Se was still evident. Two inhibitors of SeGSH-Px, D( )-penicillamine X HCl and aurothioglucose, were found to increase the lethalities of both nitrofurantoin and paraquat. Aurothioglucose was most effective when administered simultaneously with the prooxidant compounds; penicillamine increased toxicities only when administered at least 24 h before paraquat or nitrofurantoin (it decreased nitrofurantoin lethality and did not significantly alter paraquat toxicity if given simultaneously). These data support an hypothesis that the protection offered by dietary Se against the acute toxicities of the prooxidant compounds paraquat and nitrofurantoin may be provided by SeGSH Px in the chick. PMID- 3093649 TI - Effect of indomethacin in inhibition of DMBA chemical carcinogenesis. PMID- 3093650 TI - The biochemistry of nitrates, nitrites, nitrosamines and other potential carcinogens in human saliva. AB - Human whole saliva protects the oral environment in many different ways from invading pathogenic microorganisms. Human saliva is also capable of inactivating mutagenic and carcinogenic agents by various mechanisms. The peroxidation of these agents is likely to be one of the degrading reactions. However, under certain circumstances some potentially carcinogenic compounds, such as N nitrosamines, may be generated in whole saliva or--even more likely--in the saliva-gastric juice mixture after swallowing. The formation of N-nitroso compounds requires relatively high intake of nitrate e.g. from vegetable juices. Nitrate is partly reduced to nitrite by oral bacterial enzymes. The nitrosation of various secondary amines is favoured by high salivary (or gastric) concentration of thiocyanate and by low pH. The endogenous generation of N nitroso compounds may be causally related to the development of oral or gastric cancer. PMID- 3093651 TI - Enlargement of rat submandibular salivary gland induced by single amputation of lower incisor teeth. Histological, histometric and ultrastructural studies. AB - Histological, histometric and ultrastructural studies of rat submandibular salivary glands (SMG) following single amputation of lower incisor teeth were made. The SMG enlargement occurred after the tooth amputation, and its maximal increase of weight was reached 7 days later. The results of histological and histometric observations showed that the enlargement of SMG was due to both hypertrophy and hyperplasia of the acinar cells, and hypertrophic acinar cells were ultrastructurally characterized by well-developed organelles such as rough surfaced endoplasmic reticulum and Golgi apparatus which filled the entire cytoplasm. Hydropically swollen nerve endings with disappearance of vesicles were frequently found. In later stages, degenerative or necrotic cells were scattered in the acini, and the size and the structure of the remaining acinar cells became gradually similar to those of non-treated glands. The morphological changes seen in the enlarged SMG induced by single amputation of the lower incisor teeth in rat were similar in many ways to those of sialadenosis induced experimentally by active sympathomimetic drugs. PMID- 3093652 TI - Chondromyxoid fibroma of the jaws: a clinicopathological study. AB - Chondromyxoid fibroma is a benign skeletal tumor which rarely affects the jaws. Only 10 cases have been found in the literature, all of them located in the mandible. In the present articles, 2 additional cases are described, one of them being the first reported case located in the maxilla. Up-to-date clinical and pathological data of 2 reported cases and a review of the literature are presented. PMID- 3093653 TI - Modulation of class II (DR and DQ) antigen expression on gingival Langerhans cells in vitro by gamma interferon and prostaglandin E2. AB - The effect of human and murine gamma interferon (IFN-gamma) on Class II (DR and DQ) expression by human gingival Langerhans cells (LC) was examined using an organ culture system. Human and murine IFN-gamma increased the expression of both DR and DQ antigens during a 72-h period. Maximal levels of DR expression (100% of T6+ cells) were produced within 6 h of IFN-gamma treatment and were maintained during culture. DQ expression was maximal (100% of T6+ cells) at 18 h and was more labile than DR. The effect of IFN-gamma on DR and DQ was abrogated by prostaglandin E2 (PGE) while indomethacin, and inhibitor of PGE synthesis, mimicked the effect of IFN-gamma on DR and DQ expression. Gingival keratinocytes maintained their expression of DR for 72 h in the presence of gamma-IFN, but did not express DQ under any of the culture conditions used in this study. These results demonstrate that gamma-IFN induces differential expression of Class II antigens in the oral mucosa in vitro, and suggest that gamma-IFN and PGE may be involved in the control of DR and DQ antigen expression in vivo. PMID- 3093654 TI - Phenotypic identification of mononuclear cells in oral premalignant lesions and cancer by monoclonal antibodies. AB - To explore the nature and importance of mononuclear cells of different phenotypes in oral premalignant lesions and oral cancer, we studied biopsy specimens from 21 oral red and/or white lesions (6 hyperkeratosis, 3 mild dysplasia, 4 severe dysplasia and 8 squamous cell carcinoma), using monoclonal antibodies and avidin biotin-peroxidase complex staining. Peripheral blood samples (PB) from 4 normal subjects and 5 reactive lymph nodes (LN) were used as controls for the technique. T11-positive cells were the predominant phenotype (74-78%) in all cases examined. The T4/T8 ratio in severe dysplasia was significantly lower than that in mild dysplasia (p less than or equal to 0.05). These observations support the hypothesis of a role for cellular immune responses in oral premalignant lesions and oral cancer. The predominance of T cells may represent the local expression of immunity against antigens (viral or other). The decreased T4/T8 ratio observed in severe dysplasia may represent a transitory stage of local immunosuppression, which may be of critical importance for the progression into carcinoma. Phenotypic variations in mononuclear cell infiltrates in these conditions could be diagnostic value. PMID- 3093655 TI - The dentinogenic ghost cell tumor. AB - An unusual case and they of dentinogenic ghost cell tumor, a peculiar variant of calcifying odontogenic cyst, is reported. The tumor consisted predominantly of ghost cells with occasional areas of "dentinoid" in close proximity to masses of ghost cells. The presence of ameloblastoma-like nests of epithelium was characteristic of the present case and they were interpreted as a degenerative phenomenon exhibiting an inductive effect with formation of abundant ghost cells, occurring within a pre-existing ameloblastoma. The term of "dentinogenic ghost cell tumor" is employed for this unique lesion presented in this report. The literature describing the neoplastic potential of the calcifying odontogenic cyst is briefly reviewed. PMID- 3093656 TI - An experimental study into the cause of acute haemorrhagic gastritis in cirrhosis. AB - To clarify the role of endotoxaemia and congestion of the stomach in the development of acute haemorrhagic gastritis in cirrhotic patients and to investigate the mechanisms of gastric mucosal haemorrhage, the present study was undertaken using rats. Congestion of the stomach was produced by the ligation of gastric veins. Congestion of the stomach or endotoxaemia could not produce gastric mucosal haemorrhage by itself. However, petechial haemorrhage was induced when endotoxin was given to the rats with congestion of the stomach, and the gastric mucosal haemorrhage was largely prevented by administration of gabexate mesilate, an anti-kallikrein drug. Administration of bromelain, which releases prekallikrein and high molecular weight kininogen, instead of endotoxin, also induced gastric mucosal haemorrhage. These findings suggest that the cause of acute haemorrhagic gastritis may be the coexistence of endotoxaemia and congestion of the stomach due to liver cirrhosis and portal hypertension. The mechanisms of the haemorrhage may be as follows: Endotoxin-induced bradykinin acts on the dilated capillaries and small veins in the mucosa and markedly increases their permeability. PMID- 3093657 TI - Acute renal failure. II. Management of suspected and established disease. AB - Because the pathogenesis of acute renal failure is multifactorial, clinical evaluation and ancillary studies must be performed systematically to reliably differentiate the various disorders. This assessment includes measurement of the serum creatinine and urea concentrations, urine composition and flow rate, and fractional excretion of sodium. Radiodiagnostic techniques such as ultrasound, radionuclide renal scans, and nuclear magnetic resonance may provide useful anatomic and functional information. With this data base, the physician can prescribe an individualized management plan that addresses the fluid, metabolic, and nutritional necessities of the child. PMID- 3093658 TI - Serum trace elements in children receiving long-term parenteral nutrition. AB - The trace elements iron (Fe), copper (Cu), zinc (Zn), selenium (Se), chromium (Cr), manganese (Mn), nickel (Ni), rubidium (Rb), and bromine (Br) were determined in serum from 18 children, ages 4 to 65 months, who received long-term total parenteral nutrition (TPN). Nine patients (group 1) received TPN as their only source of nutrition; the other nine (group 2) ingested 30% to 70% of their total calorie requirement and received the remainder intravenously. The reference group consisted of 19 healthy children of similar age and sex distribution. Groups 1 and 2 had received parenteral nutrition for 28.4 +/- 13.7 (SD) and 23.1 +/- 17.1 (SD) months, respectively. All patients in group 1 and four in group 2 had short bowel syndrome; four in group 2 had pseudo-obstruction syndrome. Patients in group 1 had normal serum levels of Fe, Cu, and Mn, but increased levels of Zn; they had decreased serum concentrations of Se, Cr, Ni, Rb, and Br. Patients in group 2 had decreased serum levels of Mn, Cr, Ni, Rb, and Br. Those trace elements not supplemented in TPN solutions (Se, Cr, Mn, Ni, Rb, and Br) were lower in the children receiving TPN than in the control children, indicating inadequate intake of these trace elements from food and TPN solutions. However, no obvious clinical signs or symptoms of trace element deficiencies were observed. PMID- 3093659 TI - Diminished thyroid-stimulating hormone secretion associated with neonatal thyrotoxicosis. PMID- 3093660 TI - Gram-negative bacilli in human milk feedings: quantitation and clinical consequences for premature infants. PMID- 3093661 TI - Calcium metabolism in children recovering from severe protein-energy malnutrition. AB - Twenty preschool children with severe edematous protein-energy malnutrition (PEM) were studied during the first 45 days of recovery. All children received 4 g/kg/day of protein and 150 kcal/kg/day of energy from a milk-based recovery formula, providing 130-140 mg/kg/day of calcium (Ca). Children were randomized to two treatment groups, one receiving intact milk formula and the other a lactose free preparation. Both groups showed a high efficiency of intestinal calcium absorption, sustained even after the normalization of weight for height and lean body mass. The presence or absence of lactose in the diet did not affect intestinal calcium absorption, and increased stool volume in the early period of recovery in the children receiving intact milk was not associated with higher fecal Ca losses. Urinary Ca excretion was within the range reported for healthy children under a normal diet. These results suggest that therapeutic amounts of calcium should be delivered to children with PEM well beyond the normalization of body weight and lean body mass. PMID- 3093662 TI - Measurement of total body potassium in premature infants by means of a whole-body counter. AB - This paper describes a whole-body counter (WBC) specially designed to measured total body potassium (TBK) infants under 4,500 g. The counter is a "shadow shield" design and consists of a single 10 cm X 10 cm X 45 cm NaI(Tl) crystal, positioned lengthwise and shielded from environmental background radiation by a minimum of 10 cm of lead. The standard error of counting for a 2,000-s counting period is 19.9% for a 1,000-g infant and 11.9% for a 2,000-g infant. TBK of stillborn pigs, measured by the WBC, agreed to an average of 3% of TBK determined by carcass analysis in the same animals. A total of 118 measurements of TBK have been made in 50 premature infants ranging in weight between 1,100 and 3,600 g and in age between 2 and 75 days. The observed relationship of TBK with weight is described by the equation: TBK (mEq) = 0.0433Wt (g + 1.57 r = 0.92. Potassium retention per gram weight gain is estimated to be 0.043 mEq. The obtained TBK values agree well with values published by other workers but extend the range of measurement to 1,100 g. PMID- 3093664 TI - Total parenteral nutrition-associated cholestasis. PMID- 3093663 TI - Effect of cholecystokinin-octapeptide on total parenteral nutrition-induced changes in hepatic bile secretion and composition in the rat. AB - These studies investigated the ability of twice-daily administration of cholecystokinin-octapeptide (CCK-8) to prevent changes in hepatic bile secretory function and bile composition resulting from total parenteral nutrition (TPN) in young, growing rats. Bile was collected from the common duct before and during i.v. infusion of sodium taurocholate following 7 days of TPN. TPN resulted in a reduction of hepatic bile flow, reduced bile molar cholesterol and phospholipid content, and reduction of the taurocholate secretory rate maximum (SRm) and bile salt-independent bile flow (BSIF). Rats treated with CCK-8 throughout their TPN retained high bile flows, BSIF, and SRm. CCK-8 at the dose used did not correct abnormalities in the hepatic bile composition or the magnitude of bile flow generated in response to i.v. taurocholate infusion. These findings suggest that the ability of CCK-8 to maintain high bile flows during TPN may have prophylactic relevance for prevention of TPN-induced gallbladder disease. However, these studies also suggest that a component of current TPN systems induces damage to hepatic bile metabolism and excretion that is additional to that due to the reduced stimulation of bile flow that accompanies elimination of oral food intake. PMID- 3093665 TI - Immunochemical evidence for interaction between cholecystokinin C-terminal peptides and the protein inhibitor of adenosine 3',5'-cyclic monophosphate dependent protein kinase in hog terminal bile ducts. AB - The interaction of cholecystokinin (CCK) C-terminal peptides with the protein inhibitor (PK-I) of adenosine 3',5'-cyclic monophosphate-dependent protein kinase (A-PK) was studied by immunoprecipitation using anti-PK-I antibody. The binding of CCK-4 peptide to PK-I was shown to be specific; while CCK-4 enhanced precipitation of PK-I with antibody, it did not enhance precipitation of bovine serum albumin (BSA) by anti-BSA. The interaction of CCK-4 with PK-I is reversible and similar to that of urea but different from that of alkali. These results support the conclusion that CCK-C terminal peptides interact specifically with PK I. PMID- 3093666 TI - [The mode of mitomycin C uptake in rat ascites hepatoma AH130 cells]. PMID- 3093668 TI - [The HLA-A9 antigen and chronic periodontitis]. PMID- 3093667 TI - Relative bioavailability of a new transdermal nitroglycerin delivery system. AB - The purpose of this study was to measure the bioavailability of nitroglycerin from a new transdermal delivery system, Nitro-Dur II, relative to that of Nitro Dur. Twenty-four healthy male volunteers completed a two-way crossover study. Each subject randomly received Nitro-Dur (I) and Nitro-Dur II (II) for a 24-h period. Both transdermal systems had an active surface area of 20 cm2. Blood samples were collected immediately before treatment, at 0.5, 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after topical application of the units, and 30 min after the units were removed. Nitroglycerin was determined with an analytical sensitivity of 50 pg/mL using gas chromatography with electron capture detection (GC-EC). Mean steady-state concentrations of nitroglycerin were 182 and 224 pg/mL for I and II, respectively. There were no statistical differences between I and II in the pharmacokinetic parameters measured (Css, AUC, Cmax, % fluctuation). Residual nitroglycerin content was measured in each transdermal unit after application to each of the 24 volunteers. The amounts of nitroglycerin delivered by I and II were 9.78 +/- 4.11 and 10.67 +/- 4.78 mg, respectively, or approximately 10 mg in 24 h. Statistical analysis of these data using an analysis of variance indicated no significant difference between these treatments (p = 0.27). Since there were also no differences in the plasma concentrations and pharmacokinetic parameters calculated after treatment with I and II, the bioequivalence of the two delivery systems was established. PMID- 3093669 TI - Genetic differences in anticonvulsant sensitivity in mouse lines selectively bred for ethanol withdrawal severity. AB - WSP (withdrawal seizure-prone) mice exhibit approximately 10-fold more severe withdrawal convulsions than WSR (withdrawal seizure-resistant) mice after identical chronic ethanol exposure. Although WSP and WSR mice do not differ in threshold for seizures elicited by electroconvulsive shock (ECS), WSR mice are more sensitive to ethanol-induced elevation of ECS seizure thresholds. The current experiments demonstrated that WSR mice showed more ECS-induced seizure threshold elevation than WSP mice when tested after the administration of C1-C5 straight-chain alcohols. Whereas the brain concentrations of the C1 and C2 alcohols did not differ between the lines, WSP mice tended to have higher brain concentrations than WSR mice of the C3-C5 alcohols, even though they exhibited the smaller behavioral response in all cases. Thus, the difference between WSP and WSR mice was one of neurosensitivity and could not be attributed to pharmacokinetic differences. The WSR line was also more sensitive to ethchlorvynol, methyprylon, barbital, phenobarbital, pentobarbital, diazepam, valproic acid and phenytoin in this test. Examining loss of righting reflex (RR), we found that WSP and WSR mice did not differ in ED50, latency to lose RR or duration of loss of RR. Thus, the genetic anticonvulsant sensitivity difference is not simply a genetic difference in sensitivity to central nervous system depression between the lines. In summary, WSR mice were more sensitive to the anticonvulsant effects of a variety of compounds than WSP mice, suggesting that some genes influence both ethanol withdrawal seizures and ethanol's anticonvulsant effects. PMID- 3093670 TI - CGS 8216: agonist and diazepam-antagonist effects in rodents. AB - CGS 8216, a pyrazoloquinolinone benzodiazepine receptor ligand, was administered alone and concomitantly with diazepam in order to assess its agonist and diazepam antagonist properties on several behaviors in rodents. In mice, CGS 8216 (i.p.) potentiated the convulsant effects of pentylenetetrazole. Moreover, doses of 1.0 to 10 mg/kg of CGS 8216 produced dose-related antagonism of the anticonvulsant effects of diazepam. In rats, CGS 8216 (0.3-3.0 mg/kg) was without effect on the Rotarod, but produced dose-related, nonparallel shifts to the right in the diazepam dose-effect curve. Also in rats, behavior was maintained under a multiple schedule where in one component every 20th response resulted in water presentation (unpunished component) and in a second component every 20th response resulted in both footshock and water presentation (punished component). CGS 8216 produced dose-related decreases in response rates in both components, but was approximately 10-fold more potent in decreasing rates of punished responding. These effects were blocked by the benzodiazepine antagonist Ro 15-1788 (30 mg/kg i.p.). Increasing doses of diazepam (0.1-10 mg/kg p.o.) first increased and then decreased rates of punished responding but only decreased rates of unpunished responding. CGS 8216 produced a dose-related antagonism of the rate-increasing, but had little effect on the rate-decreasing, effects of diazepam. In another group of rats, behavior was maintained under a multiple fixed interval 5-min fixed ratio 20-response schedule of water presentation. CGS 8216 produced a dose related decrease in response rates in both components, but these effects were not blocked by Ro 15-1788 (30 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093671 TI - Mechanisms of extraneuronal serotonin uptake in the rat aorta. AB - The mechanisms of extraneuronal serotonin (5-HT) uptake in the rat aorta were studied. Aortic strips were pretreated with 0.1 mM pargyline and incubated with 0.1 to 9.1 microM 5-HT (5-HT, 0.02-1.60 microgram/ml including [3H]-5-HT, 0.02 microgram/ml) for 1, 2, 3 and 5 min at 37 degrees C. Accumulation of [3H]sorbitol was used to correct for extracellular distribution of this amine. The initial rate of 5-HT uptake was related linearly to the substrate concentration within the tested range. Cocaine, imipramine, desipramine (10 microM each), Na+-free solution and cooling (0 degrees C) inhibited markedly both the 1- and 5-min uptake of 5-HT. Removal of the endothelium did not affect the 5-HT uptake for 1 min but reduced slightly that for 5 min. Corticosterone (10 microM), norepinephrine (10 microM) and 6-hydroxydopamine pretreatment did not affect the uptake of 5-HT. Autoradiography demonstrated that uptake of 5-HT for 5 min in the rat aorta occurs primarily at the smooth muscle cells near the lumen. These results suggest that the rat aorta has a large capacity of cocaine-sensitive extraneuronal uptake of 5-HT. This uptake appears to occur primarily in the muscle layers adjacent to the lumen, suggesting that the muscle cells of the luminal side function differently from those from the adventitial side. The mechanism of the extraneuronal uptake of 5-HT appears to be different from that of norepinephrine and the extraneuronal uptake of 5-HT occurs initially in a nonsaturable mode and later through a Na-dependent, carrier-mediated transport. PMID- 3093672 TI - Treatment with dexamethasone increases glomerular prostaglandin synthesis in rats. AB - To determine whether chronic glucocorticoid excess influences the metabolism of arachidonic acid to prostaglandins (PGs) in the renal cortex, the authors investigated the effects of dexamethasone treatment (2.5 mg/kg/week) on the metabolism of arachidonic acid by renal cortex homogenates and microsomes and by isolated glomeruli, and on the release of immunoreactive prostanoids from isolated glomeruli incubated for 30 min in buffered salt solution at 37 degrees C. Glomeruli from dexamethasone-treated rats released, during basal incubation conditions, about twice (P less than .01) as much PGE2 and PGF2 alpha as did glomeruli from vehicle-treated rats. During incubation with arachidonic acid (33 microM) or calcium ionophore, A23187 (2.0 micrograms/ml), the release of PGE2 and PGF2 alpha from glomeruli of rats receiving dexamethasone also exceeded (P less than .01) the release from glomeruli of control rats. The rate of conversion of [1-14C]arachidonic acid to PGE2 and PGF2 alpha and to less polar metabolites having the chromatographic mobility of 5-hydroxyeicosatetraenoic acid and 12 hydroxyeicosatetraenoic acid, by isolated glomeruli and by renal cortex homogenates and microsomes from dexamethasone-treated rats, was higher (P less than .01) than the conversion by glomeruli and renal cortex homogenates and microsomes from control rats. The metabolism of arachidonic acid to the nonpolar metabolite(s) was not inhibited by indomethacin (10 microM), suggesting that it is not catalyzed by cyclooxygenase. The authors conclude that chronic dexamethasone treatment increases the release of glomerular PGE2 and PGF2 alpha and the metabolic transformation of arachidonic acid by glomeruli and by renal cortex homogenates and microsomes via both cyclooxygenase and noncyclooxygenase pathways. PMID- 3093673 TI - Phorbol dibutyrate contractions in rabbit aorta: calcium dependence and sensitivity to nitrovasodilators and 8-BR-cyclic GMP. AB - Phorbol esters activate protein kinase C and induce contraction in vascular smooth muscle. The role of Ca and the sensitivity of this response to nitrovasodilators were evaluated in rabbit aortic rings. Phorbol dibutyrate (PDB) (0.01-10 microM) elicited a concentration-dependent contraction of rabbit aortic rings. Responses to PDB in a salt solution (SS) containing 2.54 mM CaCl2 were not significantly different from those in SS containing 0 Ca and 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. Contractions to PDB (1 microM) in zero Ca SS were not reduced by depletion of the norepinephrine-sensitive pool of intracellular Ca. The Ca entry blockers verapamil (100 microM) and nifedipine (100 microM) did not affect PDB (1 microM) responses. Nitroprusside (0.1-10 microM) and nitroglycerin (0.1-10 microM) inhibited PDB contractions in both normal SS and Ca-free SS. 8-Br-cyclic GMP (100 microM) also inhibited PDB responses. Effects of PDB on 45Ca fluxes were evaluated in separate experiments. PDB (1 and 10 microM) elicited contraction, but no change in 45Ca uptake or efflux. In contrast KCl (80 mM) and norepinephrine (10 microM) elicited an increase in both influx and efflux, reflecting a rise in cytosolic Ca. The data suggest that PDB-induced contractions in rabbit aorta are independent of extracellular Ca and are not associated with a rise in cytosolic Ca as detected by calcium flux studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093674 TI - Veterans Administration Cooperative Studies Project No. 147. Part I: A multidisciplinary, multicenter experimental design for the evaluation of alternative metal-ceramic alloys. AB - The factors necessary for a comprehensive multidisciplinary, multicenter clinical study have been incorporated into CSP No. 147. The experimental design provides the potential for multiple laboratory and clinical data comparisons of alternative alloys. The study incorporates clinical performance observations with dental and medical histories that permit many unique correlations. This potential demonstrates the comprehensiveness of the CSP No. 147 study design and its contributions to clinical dental research in the evaluation of restorative materials. PMID- 3093675 TI - Disinfection method for impression materials: freedom from fear of hepatitis B and acquired immunodeficiency syndrome. PMID- 3093676 TI - Seasonal differences in function of the hypothalamic-hypophysial-ovarian axis in weaned primiparous sows. AB - Primiparous sows were fed to appetite during lactations that occurred during winter or summer, and 11.4 +/- 0.4 pigs per litter were weaned at 23.5 +/- 0.1 days of age. Sows were slaughtered at 0 or 72 h after weaning or blood samples were collected until 24 h after onset of oestrus. Sows that lactated during summer consumed less food and lost more (P less than 0.05) weight, heartgirth and backfat than those that lactated during winter. Weaning-to-oestrus interval was greater (P less than 0.05) in summer (224 +/- 25 h) than in winter (93 +/- 13 h). Content of GnRH in the hypothalamus and concentrations of LH in the anterior pituitary and serum were lower (P less than 0.05) after weaning in summer than winter. The numbers of visible ovarian follicles less than 5 mm in diameter at weaning were lower (P less than 0.05) in summer than in winter. In contrast to LH, FSH concentration in serum was higher (P less than 0.10) in summer than winter, but FSH values in the anterior pituitary were lower (P less than 0.05) in summer than in winter. Post-weaning patterns of secretion of oestradiol and follicular development differed between winter and summer. For example, in some sows weaned during the summer, transient surges of oestradiol occurred repeatedly during 0 to 280 h after weaning without provoking surges of LH. These results indicate that the period of post-weaning anoestrus in summer is prolonged because of altered activity of the hypothalamic-pituitary axis, possibly because of changes in sensitivity to the feedback of oestradiol. Lower feed intake during lactations that occur during summer may predispose the endocrine system to the aberrations. PMID- 3093677 TI - Effects of FSH and LH on incorporation of [3H]thymidine into follicular DNA. AB - To assess the roles of FSH and LH on follicular growth, after various experimental manipulations, hamster follicles were sorted into 10 stages and incubated for 4 h with [3H]thymidine. Stages 1-4 correspond to follicles with 1-4 layers of granulosa cells, respectively; Stage 5 = 5 or 6 layers of granulosa cells plus theca; Stage 6 = 7-8 layers of granulosa cells plus theca; Stage 7 = early formation of the antrum; Stages 8-10 = small, intermediate and large antral follicles, respectively. Phenobarbitone sodium injected at 13:00 h on pro-oestrus blocked the normal rise of blood FSH and LH concentrations at 15:00 h and prevented the increase of [3H]thymidine incorporation into follicles of Stages 1 9. The optimal treatment to reverse the effects of phenobarbitone was 1 microgram FSH and 2 micrograms LH injected i.p. at 13:00 h which restored DNA replication to follicles of Stages 2-10: FSH acted primarily on Stages 2-5 and LH on Stages 5 10. Injection of phenobarbitone at 13:00 h on prooestrus followed by 2.5 micrograms FSH at 22:00 h restored DNA synthesis by the next morning to follicles at Stages 1-8. In hamsters hypophysectomized at 09:00 h on the day of oestrus (Day 1), injection on Day 4 of 2.5 micrograms FSH restored DNA synthesis 6 h later to Stage 2-6 follicles. Unilateral ovariectomy on Day 3 resulted 6 h later in an acute rise in FSH and LH and change of follicles from Stage 4 to Stage 5 but, paradoxically, there was decreased synthesis of DNA in follicles of Stages 5 10.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093678 TI - A role for alternative pathway catecholamines in the regulation of steroidogenesis in cow luteal cells. AB - Incubation of bovine luteal cells with the alternative pathway catecholamines octopamine, synephrine and deoxyadrenaline at concentrations of 10(-6) to 10(-3) M enhanced the production of progesterone (P less than 0.05). Tryamine did not alter basal progesterone production (P greater than 0.05). Addition of noradrenaline and adrenaline at concentrations of 10(-4) to 10(-7) M significantly elevated the production of progesterone (P less than 0.05). The steroidogenic response to noradrenaline and adrenaline was greater than that for octopamine, synephrine and deoxyadrenaline (P less than 0.05). Response to both primary (10(-6) M) and alternative (10(-4) M) pathway catecholamines was inhibited by propranolol (10(-5) M, P less than 0.05) but not phentolamine (10( 5) M, P greater than 0.05). These results demonstrate that octopamine, synephrine and deoxyadrenaline can affect steroidogenesis by bovine luteal cells, and their action is mediated by beta-adrenergic receptors. PMID- 3093679 TI - Effects of passive immunization against oestradiol-17 beta on some endocrine values of the male lamb. AB - Passive immunization of male lambs against oestradiol-17 beta from 2 to 16 weeks of age significantly elevated androgen concentrations in plasma and depressed the median eminence content of dopamine. Removal of endogenous oestrogens had no significant effects on plasma FSH, LH or prolactin concentrations or on testicular growth and hypothalamic content of GnRH. These results suggest that endogenous oestrogens may indirectly suppress testicular androgen secretion by exerting a stimulatory influence on hypothalamic dopaminergic neurones, which in turn may inhibit GnRH secretion by the median eminence. PMID- 3093680 TI - Synthesis and aldose reductase inhibitory activity of substituted 2-oxoquinoline 1-acetic acid derivatives. AB - A number of 2-oxoquinoline-1-alkanoic acids that contain the N-acylglycine fragment found in several known inhibitors of aldose reductase were synthesized and tested in the rat lens assay. All of the target compounds were prepared by alkylation of the appropriate 2-oxoquinoline intermediates with a halo ester, followed by hydrolysis of the intermediate esters. In the rat lens assay, the 1 acetic acid derivatives 9a-e display the highest level of aldose reductase inhibitor activity with IC50 values of 0.45-6.0 microM. Modification of the 1 acetic acid moiety by esterification, substitution of an alpha-methyl group, or insertion of an additional methylene unit results in reduced inhibitory potency. Structure-activity data also suggests that both the benzene and 2-oxopyridine rings of 9a-e contribute substantially toward activity and that inhibitory potency is influenced by aromatic ring substituents. PMID- 3093681 TI - Synthesis of 8-amino-3-deazaguanine via imidazole precursors. Antitumor activity and inhibition of purine nucleoside phosphorylase. AB - 8-Amino-3-deazaguanine (15), an analogue of both 3-deazaguanine (1) and 8 aminoguanine (6), an antitumor agent and a purine nucleoside phosphorylase (PNP) inhibitor, respectively, was synthesized from the ammonolysis of an imidazole precursor, methyl 2-(benzoylamino)-5-(cyanomethyl)-1H-imidazole-4-carboxylate (13). The requisite imidazole, methyl 2-(benzoylamino)-4-(methoxycarbonyl)-1H imidazole-5-acetate (11), was prepared from the monoheterocyclic rearrangement of dimethyl 3-[(5-phenyl-1,2,4-oxadiazol-3-yl)amino]-2-pentenedioate (10) by NaH/DMF. Ammonolysis and subsequent dehydration of 11 provided the penultimate imidazole intermediate 13. Its deprotected (NaOMe/100 degrees C) product, methyl 2-amino-5-(cyanomethyl)-1H-imidazole-4-carboxylate (14), was also converted to 15. 8-Amino-3-deazaguanine, as its methanesulfonic acid (mesylate 7), exhibited an inhibition constant (IC50) of 9.9 microM against isolated mammalian PNP. It was a very weak inhibitor of T and B cell growth and did not enhance 2' deoxyguanosine toxicity in the same cells. 8-Amino-3-deazaguanine mesylate was not significantly active in L1210 cells in vitro or L1210 leukemic mice. Thus, the amino group introduced in the 8-position of 3-deazaguanine enhances its PNP activity but diminishes its antitumor activity. PMID- 3093682 TI - Chloroalanyl antibiotic peptides: antagonism of their antimicrobial effects by L alanine and L-alanyl peptides in gram-negative bacteria. AB - A large number of structurally diverse di- and tripeptides containing the alanine racemase inactivator beta-chloro-L-alanine (beta-Cl-LAla) have been synthesized, and their antibacterial properties in vitro have been evaluated. The dipeptides 1, 3-6, and 8-17 and the tripeptide 20 are all broad-spectrum antibacterial agents with considerable potency against both Gram-positive and Gram-negative species, but none of these peptides improves dramatically on the antibiotic efficacy of the previously described beta-Cl-LAla-beta-Cl-LAla, 9 (Cheung, K. S.; Wasserman, S. A.; Dudek, E.; Lerner, S. A.; Johnston, M. J. Med. Chem. 1983, 26, 1733). Gram-negative microorganisms, such as Escherichia coli, Hemophilus influenzae, Shigella flexneri, and Enterobacter species are consistently resistant to any haloalanyl peptide containing an alanyl residue, such as the dipeptide LAla-beta-Cl-LAla (2) and the tripeptides LMet-LAla-beta-Cl-LAla (7), LAla-LAla-beta-Cl-LAla (18), and LVal-LAla-beta-Cl-LAla (19). Correspondingly, these same organisms are protected from the bactericidal effects of 9 by supplementation of the growth medium with LAla or LAla-LAla. Escherichia coli JSR O exposed to 9, but protected from lysis by sucrose stabilization, has only about 10% the normal level of intracellular alanine racemase activity. But when these cells are cultured in the presence of 9 with LAla supplementation, or in the presence of 2 with no supplementation, the alanine racemase levels are only about 20-30% below control values. These findings suggest that the resistance of Gram negative species to chloroalanyl peptides containing alanyl units arises from the ability of LAla to protect the targeted racemase from inactivation by beta-Cl LAla in vivo, an event which otherwise leads to cell death and lysis. Inactivation of alanine racemase in Gram-positive organisms appears not to be the cellular event that confers sensitivity of these species to a haloalanyl peptide. PMID- 3093683 TI - Natural killer cell activity in patients with inflammatory bowel disease. AB - It has been suggested that the "natural killer" (NK) cell may play an important role in immune surveillance against tumors and viral-infected cells. With the use of 51Cr-labeled K-562 as target cells, we assessed natural killer cell activity in patients with inflammatory bowel disease (IBD). In ulcerative colitis (UC) patients' NK cell activity in the remissive and active stages was not significantly different with normal controls. In Crohn's disease (CD) patients' NK cell activity was significantly below normal levels in both remissive and active stages. Furthermore, in the active stage NK cell activity was significantly lower than that in the remissive stage in CD patients. Using the anti-Leu-11a monoclonal antibody, we quantified the number of circulating NK cells in CD patients. Decreased NK activity in CD patients is most likely not the consequence of diminished numbers of NK cells or of maturational defects of NK precursor cells. Macrophage seems to be one of the factors related to decreased NK cell activity. Further, impairment of NK cell activity in CD patients is reversible. It is possible that NK cell activity in CD patients recovers to the normal level. PMID- 3093684 TI - The influence of 7,12-dimethylbenzanthracene on natural killer (NK) cell function in rats. AB - The administration to 2 strains of rat (Alderley Park and Sprague Dawley) of 40 (2 X 20) mg of 7,12-dimethylbenzanthracene (DMBA) on a single day caused a transient depression of NK cell function. The splenic natural cytotoxic capacity of both DMBA treated and control animals was augmented by inclusion within the assay of interferon (IFN) but IFN failed to restore carcinogen-treated splenocyte cytotoxicity to normal values. Splenocyte populations from DMBA treated animals exhibiting reduced cytotoxic activity possessed normal frequencies of target binding lymphocytes suggesting that the impairment of reactivity was attributable to a defect in the post-recognitive stage of NK mediated lysis. Administration of DMBA was not associated with a reduction in spleen weight or cellularity or with an impairment of splenic lymphocyte responsiveness to phytohaemagglutinin (PHA) indicating that depressed NK cell function was not a result of general lymphotoxicity. These data confirm previous reports that administration of chemical carcinogens may be associated with a depression of NK cell function. PMID- 3093685 TI - Acute pancreatitis: a complication of Foley catheter gastrostomy. AB - Acute pancreatitis can be caused by inadvertent migration into the duodenum of the inflated balloon of a Foley gastrostomy catheter. The clinical picture is that of an acute abdomen. The diagnosis is made with a high index of suspicion and confirmed by marked elevation of serum and urine amylase levels. The treatment consists of repositioning of the gastrostomy tube and supportive therapy. Careful external fixation of the tube to the abdominal wall can prevent this complication. PMID- 3093686 TI - Characterization of human IMR-90 fibroblasts as a model system for the study of chemical carcinogenesis in vitro. AB - The effects of chemical carcinogens on various aspects of cellular metabolism were measured in human IMR-90 fibroblasts. These studies were undertaken to assess the ability of IMR-90 cells to be used for the study of chemical carcinogenesis in vitro. It was found that chemical carcinogens inhibited DNA synthesis in synchronous cultures of IMR-90 fibroblasts; the effective concentrations of carcinogens showing effects in this system were lower than for other published in vitro cell assay systems; compounds that require metabolic activation to a carcinogenic form demonstrated the ability to inhibit DNA synthesis in IMR-90 fibroblasts; a fluorometric determination of aryl hydrocarbon hydroxylase (AHH) activity in IMR-90 cells revealed a low level of inducible AHH; IMR-90 cells can metabolize 7,12-dimethylbenzanthracene (DMBA) to compounds that are identified as metabolites of DMBA in vivo. PMID- 3093687 TI - Effect of ammonium metavanadate on the murine immune response. AB - Female B6C3F1 mice were exposed to ammonium metavanadate (NH4VO3) by intraperitoneal injection every 3 d at 2.5, 5.0, or 10 mg V/kg for 3, 6, or 9 w and were then assayed for alterations in immunoresponsiveness. Resistance to Escherichia coli endotoxin lethality increased in a dose-dependent manner up to 6 w of exposure, while resistance to viable gram-positive Listeria lethality was depressed in a dose-dependent manner. Comparison of LD20 values indicated a 250 fold decrease in resistance to Listeria at the lowest vanadium exposure and a 40% increase in resistance to endotoxin after the highest vanadium exposure. Peritoneal macrophage phagocytic capacities were decreased in a dose-dependent manner, but viabilities remained unaffected. Rosetting capacity of splenic lymphocytes was increased following vanadium exposure. Liver and splenic enlargement was observed, and examination of splenic tissue indicated enhanced formation of megakaryocytes and red blood cell precursors. Subchronic exposure to vanadium may thus disrupt the normal function of the immune system. PMID- 3093688 TI - Glial culture on artificial capillaries: electron microscopic comparisons of C6 rat glioma cells and rat astroglia. AB - The functional association of astroglial footplates with blood vessels is important because astrocytes may provide a channel between the blood and neurons deeper in the brain parenchyma for the passage of ions and metabolites. This hypothesized function is very difficult to study in vivo or in monolayer cultures. We have produced a three-dimensional cell culture model of perivascular astroglia by means of an artificial capillary system. Conventional primary cultures of astroglia were first prepared from neonatal rat cerebral hemispheres in 75-cm2 tissue culture flasks. After 25 days, the cells were seeded in Amicon Vitafiber hollow fiber culture vessels. Direct seeding of brain cell suspensions was not successful. A culture unit consists of a bundle of hollow, semi-permeable polysulfone fibers encased in a plastic shell. The fibers were coated with fibronectin and bovine serum albumin, and astroglia were seeded on their outer surfaces. Warmed medium was pumped through the lumina of the fibers. After 13 days the cells were fixed with paraformaldehyde and examined. Scanning electron microscopy revealed the tubes to be uniformly covered with astroglia with short processes that contacted nearby cells. Transmission electron microscopy showed glial filaments and gap junctions. Astrocyte cultures were compared morphologically to C6 rat glioma cells in hollow fiber culture. The astrocytes formed a monolayer, whereas C6 cells formed a stratified culture. Furthermore, C6 cells did not form gap junctions. Astrocytes have been hypothesized to take up K+ discharged to the extracellular space by depolarizing neurons and move it to areas of low concentration, i.e., to act as a K+ spatial buffer. Our culture system should permit direct testing of this hypothesis. PMID- 3093689 TI - [Acute toxicity test on dermal application of NT-1 tape and 10% nitroglycerin (NT 1 ointment)]. AB - An acute toxicity of NT-1 tape was investigated in mice, rats and rabbits, and also an acute toxicity of NT-1 ointment in rabbits. An irritation of NT-1 tape was investigated in rabbits. Dead animals treated with NT-1 tape or ointment were not observed in reliable maximum administration dose of 0.88 mg/body as GTN (nitroglycerin) in mice (male; about 29.1 mg/kg, female; about 35.2 mg/kg), of 3.96 mg/body as GTN in rats (male; about 26.0 mg/kg, female; about 28.9 mg/kg) and of 480 mg/kg as GTN in rabbits. There were not toxic signs in mice and rats. The below findings were observed in rabbits treated mainly with NT-1 ointment: decreased spontaneous activity, decreased reactivity to various stimuli such as sound and touch, and behavior of binding food box. However, the rabbits recovered from those abnormal behavior in a day. Any body weight changes and any autopsy findings attributable to NT-1 tape or ointment were not observed in mice, rats and rabbits. The effects on ECG were not observed in rabbits. The GTN absorption ratio in rabbits treated with NT-1 ointment was thought to be 60-70% from GTN residual ratio. The skin irritation was not observed in rabbits treated with NT-1 tape. PMID- 3093690 TI - [Percutaneous subacute toxicity study of 10% nitroglycerin (NT-1 ointment) in rabbits]. AB - NT-1 ointment is a compound containing 10% nitroglycerin which is topically applied to the skin for angina pectoris. The subacute toxicity of this compound was examined by the continuous application for 5 weeks to the shaven skin of rabbit back at dose levels of 240, 120 and 60 mg/kg, and the recovery was examined 3 weeks after withdrawal of the drug. No special skin response to the NT 1 ointment was observed other than an erythema of the grading 2-3 Draize points, while the control ointment, which was the base ointment without nitroglycerin, showed a higher grade of erythema equivalent to 4 Draize point with crusta formation. No relationship between the dose level of NT-1 ointment and the skin response was observed, and skin response was thought to be caused mainly by the base ointment. The skin response gradually reduced even during the application period, and the skin response disappeared within a few days after withdrawal of the ointment. Histological examination of the treated skin at the respective ends of the application and recovery periods showed thickening of the corneum and epithelial layer, round cell infiltration and fibrosis in the corium, and development of hair folliculi in the subdermis. No systemic effect of the topically applied NT-1 ointment was observed in the majority of the animals, either in behavior, hematologic and electrocardiographic examination, food consumption, body weight change or urinalysis. PMID- 3093691 TI - [Percutaneous chronic toxicity study of 10% nitroglycerin (NT-1 ointment) in rabbits]. AB - A chronic toxicity test of 10% nitroglycerin (NT-1 ointment) was carried out in male NZW rabbits. NT-1 ointment was applied to the back skin for 26 weeks at daily doses of 15, 60 and 240 mg/kg as nitroglycerin itself, and 5-week withdrawal period was followed. Topical dermal responses to NT-1: Macroscopically, erythema, edema, scales, papules and dermal thickening were observed in response to NT-1 ointment. In the withdrawal period, however, all of them disappeared. Histopathologically, thickening of epidermis and cell infiltration were observed in response to NT-1 ointment. In addition, elongation of rete ridges and Touton giant cells were found only in 60 and 240 mg/kg groups, and hyperkeratosis only in 240 mg/kg group. At the end of withdrawal period, Touton giant cells were still found in 60 and 240 mg/kg groups, although the other dermal reactions disappeared. Systemic responses to NT-1 ointment: A slight increase in the excretion of loose or mucous feces was observed in 240 mg/kg group. The weights of right and left kidneys were increased by the administration of 240 mg/kg NT-1 ointment, and a similar trend was seen also in the weight of heart, although there found no such among-group differences at the end of withdrawal period. White blood cells, especially neutrophils, and gamma-globulin fraction were increased in response to 240 mg/kg NT-1 ointment. In conclusion, a no-toxic effect dose of NT-1 ointment as nitroglycerin itself was considered to be 15 mg/kg/day for the skin and 60 mg/kg/day for the general somatic system. PMID- 3093692 TI - [Teratological test of 10% nitroglycerin (NT-1 ointment) in rabbits]. AB - A teratological test of 10% nitroglycerin (NT-1 ointment) was carried out in New Zealand White rabbits. Pregnant rabbits were treated percutaneously with NT-1 ointment from day 6 to 18 of gestation at dose levels of 15, 60 and 240 mg/kg/day as nitroglycerin itself. All pregnant rabbits were killed on day 29 of gestation, and the influences of NT-1 ointment upon the performances of dams and fetuses were examined. During the treatment period, erythema was observed on the treated dorsal skin in all groups excluding the nontreatment control group. However, it disappeared soon after the cessation of NT-1 ointment administration. Influences of NT-1 ointment administration were not found at any dose levels on the food consumption and body weight changes of pregnant rabbits. In addition, influences of NT-1 ointment on the reproductive performance of dams and the development of fetuses were not observed at any dose levels. Therefore, the non-effect dose of NT-1 ointment on reproductive performance of dams and fetal development in rabbits was estimated to be 240 mg/kg/day and more as nitroglycerin itself. PMID- 3093693 TI - Outpatient pediatric urological surgery: techniques for a successful and cost effective practice. AB - Of 674 operations performed in the pediatric urology division between January and October 1984, 62 per cent were done on an outpatient and 12 per cent on a 1-night stay basis. The outpatient procedures included major proximal hypospadias repairs and intra-abdominal procedures, as well as inguinal, penile, scrotal and endoscopic procedures. No child required subsequent hospitalization. This successful approach was contingent upon proper patient selection, patient and family education, modern anesthetic and monitoring techniques, and careful followup. For elective procedures, such as hypospadias repairs, patients are operated on when they are 6 to 18 months old. Modern anesthetic techniques include isoflurane to maintain a light level of general anesthesia and adjunctive regional blocking procedures. The availability of a physician support service on a 24-hour basis is fundamental to the success of this approach. Benefits include patient, parental and physician satisfaction, diminished potential for nosocomial disease transmission and avoidance of the emotional stress of parent-child separation. Increased use of outpatient surgery is a means to produce a significant decrease in the cost of medical care. PMID- 3093694 TI - Inverted Y duplication of the ureter in association with ureterocele and bladder diverticulum. AB - We report a case of inverted Y duplication of the ureter in association with an obstructing ectopic ureterocele and paraureteral diverticulum. Preoperative radiological studies demonstrated the ureterocele and diverticulum but they failed to show the duplex distal ureter. The duplicated section of ureter was excised and a Cohen reimplantation was performed. The presence of a large ureterocele obstructing the bladder neck, a diverticulum, failure of reflux into the ectopic segment and poor function of the affected kidney all contributed to the difficulties in establishing a preoperative diagnosis. PMID- 3093696 TI - Amniotic fluid embolism. PMID- 3093695 TI - alpha-Difluoromethylornithine enhancement of 14C-putrescine uptake by an androgen dependent prostatic tumor. AB - Putrescine is a potential scanning agent for metastases of prostatic carcinoma. We examined the in vivo uptake of [14C]-putrescine by the Dunning R3327H Copenhagen rat prostatic tumor and by other tissues, and conclude that: The uptake of [14C]-putrescine by the tumor was higher than that of the normal dorsolateral prostate, but similar to that of the ventral prostate. Tumor accumulation of [14C]-putrescine was enhanced 38% in intact and 45% in castrated animals by pretreatment with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor. Further enhancement of tumor uptake (94% in intact and 201% in castrated animals) was achieved by combining DFMO pretreatment with androgen stimulation. Oral administration of methyl-glyoxal bis (guanylhydrazone) (MGBG) increased intestinal uptake of [14C]-putrescine, while oral administration of unlabeled spermine and putrescine decreased it. Dexamethasone decreased the uptake of [14C]-putrescine by the spleen and intestine, but also reduced the prostatic uptake to a considerable extent. These observations are useful for the design of a putrescine-based scan for metastases of prostatic carcinoma. PMID- 3093697 TI - Eflornithine treatment of Pneumocystis carinii pneumonia in AIDS. PMID- 3093698 TI - Dementia. Council on Scientific Affairs. AB - Dementia has emerged as a national health concern. The demographics of our aging population suggest that this concern can only become more acute. For families that have a member with a primary dementing illness, this concern often becomes an all-consuming one. At present, our understanding of the primary dementias, especially Alzheimer's disease, is incomplete, and thus, most cases of primary dementia progress irreversibly. Nevertheless, there is much in the way of treatment, care, and support that can be provided by the practicing medical community to sustain the viability and vitality of patient and family. PMID- 3093699 TI - Guidelines for use of total parenteral nutrition in the hospitalized adult patient. A.S.P.E.N. Board of Directors. PMID- 3093700 TI - Report of a research workshop: branched-chain amino acids in stress and injury. PMID- 3093701 TI - Branched-chain amino acid interactions in skeletal muscle: isoleucine and L alloisoleucine. AB - Parenteral administration of a mixture of branched-chain amino acid (BCAA) solutions is known to alter plasma levels of the BCAA (ILE, LEU, VAL), their corresponding alpha-ketoacids (KMV, KIC, KIV) and L-alloisoleucine (ALLO), a stereoisomer of ILE. Although variously formulated mixtures of BCAA are administered, the metabolic implications of individual BCAA interactions have been only partially elucidated. Using the incubated, isolated, and intact rat epitrochlearis muscle, we measured the effect of graded increases (0.05, 0.10, 0.5, and 1.0 mM) in media concentrations of a single BCAA or ALLO on (1) the rate of decarboxylation of the other BCAA, and (2) the release of branched chain ketoacids from muscle. A graded increase of media ILE concentration to 1.0 mM changed the decarboxylation of LEU by -28%, and the release of KIC by +23%, but VAL decarboxylation increased by +25%, and the release of KIV declined by -56%. A graded increase of media LEU to 1.0 mM increased ILE decarboxylation by +146%, and its corresponding ketoacid (KMV) by +61%. However, VAL decarboxylation changed by only +25% and KIV release declined by -65%. A graded increase in media VAL to 1.0 mM accelerated ILE decarboxylation by +37%, but KMV release was unchanged. Similarly, LEU decarboxylation fell by -26%, and the release of KIC by only +6%. ALLO 0.025 mM increased ILE release by +55% but had an inconsistent effect on ILE decarboxylation and did not alter protein synthesis or degradation (estimated by phenylalanine incorporation and tyrosine release, respectively). Increasing ILE did not affect ALLO release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093702 TI - Energy metabolism and substrate oxidation as possible factors for net protein accretion in growing rats. AB - This study describes an experimental model with growing rats in which we have measured energy expenditure and substrate oxidation as possible factors for regulation of net protein synthesis in intravenously fed growing rats. Orally fed rats were used as a reference group. Rats were given intravenous nutrition for 10 days at a high (350 kcal/kg/day) and a low (270 kcal/kg/day) energy level with four different fat-to-carbohydrate compositions at each energy level: N (no fat), L (low fat, 6% nonprotein calories), M (medium fat, 30% nonprotein calories) and H (high fat, 60% nonprotein calories). Continuous O2-consumption and CO2 production of the animals were measured. Whole body substrate oxidation was calculated from respiratory gas exchange and nitrogen excretion. Body composition was assessed in all animals at the end of infusions. Energy balance with zero growth was reached at 240 kcal/kg/day. Growth rate was normal in animals receiving 350 kcal/kg/day compared with freely eating reference animals irrespective of the glucose-to-fat ratio of the intravenous solutions. Animals on 270 kcal/kg/day showed retarded growth rate, but the differences in growth rate among the groups were mainly explained by carcass fat. Net protein accretion did not differ among most of the groups irrespective of intravenous or oral intake at different levels. The whole body oxidation rate of glucose was directly proportional to the infusion rate of glucose, while the net fat oxidation was inversely correlated to the infusion rate of glucose. The oxidation rate of amino acids and proteins was not directly correlated to the oxidation of glucose or fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093703 TI - Cardiac function during protein malnutrition and refeeding in the isolated rat heart. AB - In an attempt to elucidate the effect of protein restriction and subsequent refeeding on cardiac muscle function, 133 rat hearts were studied on a Langendorff perfusion apparatus: 19 normal controls, 55 rats during 6 weeks of protein restriction, and 59 rats during 6 weeks of refeeding following starvation. During starvation animals lost 14.3% of body weight and 12.8% in heart weight, both to be gained upon refeeding. Both developed force and force velocity tended to decrease in starving rats compared to control or refeeding rats. This trend was present at time 0, but more so after 60 min of perfusion. Furthermore, these differences became even more obvious and significantly different at the higher heart rates of 300 and 400 beats/min, and less so at 100 or 200 beats/min. These protein malnutrition-associated cardiac function derangements reversed almost completely to normal upon refeeding. PMID- 3093704 TI - Improved nutritional management reduces length of hospitalization in intractable diarrhea. AB - Sixteen patients were managed by one of two specific refeeding protocols to compare the efficacy of two enteral formulas in the nutrition restoration of infants with intractable diarrhea (IDI). The protocols outlined specific nutritional therapy including transition from parenteral to enteral nutrition; concentration, volume, and steps of advancement of formulas. Patient progress was monitored daily. Average length of stay, number of days on parenteral nutrition support, and number of formula changes for the IDI protocol groups were compared with a retrospective chart audit group of 29 IDI patients. The protocol groups had substantially fewer days of parenteral nutrition support, significantly fewer formula changes (p less than 0.01), and fewer days of hospitalization. The differences resulted in $14,750 of charges saved per protocol patient. PMID- 3093705 TI - Clinical experience with the multiple lumen central venous catheter. AB - One hundred four multiple lumen central venous catheters (MLC) were evaluated in 74 seriously ill patients. Eighty percent of the catheters were placed in an intensive care unit. Each MLC served as access for a mean of 4.5 different functions, including infusions, central venous monitoring and phlebotomy. Complications occurred with 16 MLC (15.4%), including two aberrant placements, 10 mechanical problems, and four septic catheters (3.8%). Simultaneous administration of TPN and other infusions through MLC did not affect the rate of catheter sepsis. MLC are well tolerated and cost effective. They increase the comfort of patients who require complex venous access or who lack peripheral veins. They allow safe concurrent administration of TPN, medications, and central venous monitoring. PMID- 3093706 TI - Microbial growth patterns in a total parenteral nutrition formulation containing lipid emulsion. AB - Microbial growth of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans was evaluated in a standard amino acid-dextrose based total parenteral nutrition (TPN) solution, 10% lipid emulsion, and a combined TPN formulation containing amino acids, dextrose, and lipid emulsion. At an initial inoculum of 10(4) CFU/ml, all three bacterial organisms grew well in 10% lipid emulsion, died in the standard solution and grew only minimally or died in the combined formulation. C. albicans grew in all three formulations at an initial inoculum of 10(4) CFU/ml; however, at an initial inoculum of 10(2) CFU/ml, which approximates touch contamination, growth of Candida in the standard and combined formulations was less than 1 log at 24 hr in contrast to the 10% lipid emulsion which showed significant growth greater than 2 log at 24 hr. It is concluded that a 24-hr infusion time is safe for the combined TPN formulation used in this study. This should result in significant cost savings compared to the previously recommended 12-hr infusion time. PMID- 3093708 TI - Bacterial contamination of enteral nutrient solutions: intestinal colonization and sepsis in mice after ingestion. AB - Contaminated enteral nutrient solution (ENS) was used to assess the risks of intestinal colonization and invasive sepsis using normal mice. Dilute Osmolite containing 10(6) Group B Streptococci/ml given for 2 to 10 consecutive days resulted in the detection of organisms by rectal washing sampling and in the recovery of 10(3) to 10(4) organisms from the cecum, large intestine, and rectum. Only 10(1) organisms survived in the small intestine. Colonization, or the persistence of organisms for 10 days after exposure, was produced after 2 days of ingestion in 44% of animals and in 100% after exposure for 5 days. There were 39 septic deaths. During the 7-day ingestion interval 15 died and 24 died within 10 days after exposure. The risk of sepsis was highest for young mice. Ways to minimize bacterial contamination of ENS intended for administration to patients are discussed. PMID- 3093707 TI - Bacterial/fungal growth in a combined parenteral nutrition solution. AB - Appropriately mixed, compatible solutions of glucose, amino acids and lipid have recently become available for clinical use. While a single hyperalimentation solution has several advantages over the conventional two-bottle technique, its effect on infusion-related septicemia is unknown. An in vitro, mock infusion system identical to that used in our new-born intensive care unit was set up to assess the relative growth rates of three microorganisms in several parenteral nutrition mixtures. Growth of Staphylococcus epidermidis, Escherichia coli and Candida albicans was measured in seven different alimentation solutions, including two combined solutions. Generally, microbial growth was the same or decreased in combined solutions as compared to fat alone although considerably greater than that observed in nonlipid containing solutions. In addition, the ability of these organisms to pass in-line terminal filters of pore size 0.22 and 1.2 microns was assessed. PMID- 3093709 TI - Phosphate balance and distribution during total parenteral nutrition: effect of calcium and phosphate additives. AB - Hypophosphatemia is occasionally observed during total parenteral nutrition (TPN). The phenomenon was recognized since the introduction of TPN and was attributed to preexisting phosphate deficits and inadequate phosphate supplements. Because of the close relationship between phosphate and calcium metabolisms, we speculated that calcium additives may also influence phosphate balance and distribution during TPN. We tested this hypothesis in previously fasted animals receiving TPN with variable amounts of calcium and maintenance or no phosphate. Fasting resulted in considerable losses of phosphate in the urine. Refeeding (with TPN) after fasting produced hypophosphatemia but only in animals receiving calcium additives and no maintenance phosphate in the solution. Addition of moderate or large amounts of calcium decreased phosphate in the muscle in groups not receiving maintenance phosphate. There were no significant changes in bone phosphate. Increasing calcium intake was accompanied by significant and progressive reductions in urine phosphate in animals receiving maintenance phosphate, thus increasing net phosphate retention in those groups. In other respects, refeeding with TPN after fasting displayed features compatible with those of the phosphate depletion syndrome, including hypophosphatemia, hypophosphaturia, hypercalcemia, and hypercalciuria. The magnitude of change in these parameters seemed to be dependent upon the amount of calcium added and the availability of phosphate in the solution. PMID- 3093710 TI - Nutritional management of thoracic duct fistulas. A comparative study of parenteral versus enteral nutrition. AB - Thoracic duct fistulas represent one of the serious technical complications of head and neck surgery, and reoperation for control of the leakage involves considerable morbidity and mortality. In an attempt to define the possibilities of both enteral and parenteral nutrition in the treatment of this problem, two comparable groups of patients were given, respectively, one or the other of these modalities. Significant advantages for parenteral nutrition could be demonstrated regarding duration of therapy (p less than 0.05), closure rate (p less than 0.05), and nutritional response (p less than 0.05). These results strongly recommended the utilization of parenteral nutrition in the primary therapy of thoracic duct fistulas. PMID- 3093711 TI - Cardiac tamponade: a complication of central venous hyperalimentation. AB - Complications from central venous catheterization for administration of parenteral feeding solutions are common and well documented. In a recent series, complications from catheter placement were reported as 4.8%. We report the case of a patient with cardiac tamponade while receiving parenteral hyperalimentation through a polyurethane central venous catheter. PMID- 3093712 TI - Neutropenia due to copper deficiency in total parenteral nutrition. AB - Copper (Cu) deficiency has been reported both in pediatric and adult patients on total parenteral nutrition (TPN). Manifestations of Cu deficiency are usually hematologic in the adult. A 56-yr-old patient with a history of subtotal gastrectomy underwent massive small bowel resection and partial colectomy in 1977. TPN was initiated. Intravenous (iv) trace mineral supplements were not available in 1977 at our institution. By June 1978, the patient manifested neutropenia with a white blood cell (WBC) count of 2000/mm3 and 39% neutrophils or a total neutrophil count (TNC) of 780/mm3. The serum Cu level at that time was 5 micrograms/dl (normal, 70-140), and the serum zinc (Zn) level was low, although within normal limits. Oral supplementation with Cu and Zn tablets proved ineffective. Twice weekly infusions of fresh frozen plasma were begun in April 1979, and intravenous chromium supplementation started in September 1979, but neither the WBC count nor the TNC improved. Intravenous Cu and Zn were approved in October 1979, and were added to the TPN formula. Within 2 weeks, the WBC count rose to 6300/mm3, and the neutrophils increased to 83% with a TNC of 5229. After 12 weeks, the serum Cu level rose to 80 micrograms/dl. The increase in WBC count and percentage of neutrophils can be attributed to the addition of Cu to the TPN infusate. PMID- 3093713 TI - Nutritional support for an achondroplastic dwarf: a case report. PMID- 3093714 TI - Pediatric parenteral nutrition management using a comprehensive user-friendly computer program designed for personal computers. AB - The use of parenteral nutrition is becoming more widespread. The need for individualized parenteral nutrition solutions in pediatric patients makes the ordering and preparation of these solutions more complex and error-prone. A computer program is described which performs comprehensive management of parenteral nutrition by assisting in accurately ordering and preparing parenteral nutrition solutions. It also performs extensive error-checking and provides additional nutritional information. Data base management is also a feature which permits future large scale analysis of parenteral nutrition data for research purposes. This program, designed to run on a personal computer, is very comprehensive, yet flexible and user-friendly. PMID- 3093715 TI - The "all in one" system for TPN causes increased rates of catheter blockade. PMID- 3093717 TI - Bacterial causes of infantile diarrhoea as influenced by age and feeding practices. PMID- 3093716 TI - Choice of diuretics in cirrhotic ascites. PMID- 3093718 TI - Aflatoxin in uncooked market commodities: spices. PMID- 3093719 TI - Urinary excretion of aflatoxin and liver cancer in Karachi. PMID- 3093720 TI - 'Albendazole' in intestinal helminthiasis. PMID- 3093721 TI - Demonstration of a renoperitoneal fistula by radionuclide renal scanning: a case report. PMID- 3093722 TI - Prostaglandins, menstruation, and menstrual disorders. PMID- 3093723 TI - Neurovirological research of encephalitides in and around Karachi. The clinical aspects (interim report). PMID- 3093724 TI - Epidemiology of subacute sclerosing panencephalitis (SSPE) and other encephalitides in Karachi area; a progress note. PMID- 3093725 TI - Estimated mortality rate by sex-age and death causes in Karachi. PMID- 3093726 TI - Seroepidemiological research on viral encephalitis in Karachi Pakistan- preliminary report. PMID- 3093727 TI - Gastric leiomyoma and its manifestations in Nigerians. A series of 10 patients. PMID- 3093728 TI - [In vivo combination effects of astromicin and beta-lactam antibiotics against Pseudomonas aeruginosa]. AB - Astromicin (ASTM, Fortimicin) is a pseudodisaccharide aminoglycoside antibiotic. The ASTM exhibited excellent activity against Gram-positive and Gram-negative bacteria but was only weakly active against Pseudomonas aeruginosa. In vitro synergistical activities of ASTM combined with beta-lactam antibiotics have been reported against P. aeruginosa previously. In this paper, we investigated the in vivo combination efficacies of ASTM and beta-lactam antibiotics (latamoxef (LMOX), cefoperazone (CPZ), piperacillin (PIPC) and cefsulodin (CFS) against experimental infection with P. aeruginosa in both normal and immunosuppressed mice. In normal mice, the combination of ASTM with these beta-lactam antibiotics produced significantly greater protective effects than the single use of individual antibiotics against both strains of P. aeruginosa BMH No. 1 and E-2. In mice immunosuppressed with cyclophosphamide, the combination of ASTM with LMOX or CFS also exhibited synergistic protective effects against P. aeruginosa BMH No. 1, but PIPC and CPZ did not. From the above results, the combination therapy of ASTM with beta-lactam antibiotics appeared to be effective against experimental infections with P. aeruginosa in mice. PMID- 3093730 TI - [A case of posttransfusion hepatitis showing epithelioid granuloma in the bone marrow with pure red cell aplasia (PRCA)]. PMID- 3093729 TI - [Effect of combined application of coenzyme Q10 with adriamycin--with special reference to hemorrhagic diathesis]. PMID- 3093731 TI - [Progress in chemotherapeutic agents--penicillins]. PMID- 3093732 TI - [Prophylactic administration of antimicrobiological agents and reflection thereon -prevention of infections in hematologic diseases and malignancies]. PMID- 3093733 TI - [Drug resistance of bacteria and countermeasures--current status of resistance. 3. Glucose-nonfermentative bacteria]. PMID- 3093734 TI - [Sialidosis]. PMID- 3093735 TI - [Participation of IgG in EDTA-dependent pseudothrombocytopenia by scanning electron microscopic study]. PMID- 3093736 TI - [Application of middlebrook 7H-10 agar medium for rapid detection of mycobacteria]. PMID- 3093737 TI - A simple technique for long-term intravenous feeding in unrestrained rats. AB - A model for parenteral nutrition of unrestrained rats is described. Apparatus and nutrient solutions are very simple, inexpensive, and commonly available. The major survival time is at least 6-8 weeks. During the parenteral nutrition the rats gain weight and are in a excellent general health. The cumulative nitrogen balance is highly positive with a retention of 95%. PMID- 3093738 TI - Cell-mediated immune response in mice during the two-step carcinogenesis experiment by 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13 acetate. AB - Cell mediated immune response in ICR mice during the two step carcinogenesis experiment induced by DMBA plus TPA was followed by determining the delayed type hypersensitivity to two antigens, i.e. DNFB applied to skin and SRBC injected intraperitoneally. In mice developing tumors from 3 to 15 weeks after DMBA initiation, delayed type hypersensitivity to DNFB was suppressed to as low as 30% that of normal mice. This suppression was not recovered by treatment of indomethacin. No difference in delayed type hypersensitivity to SRBC was observed on between the mice on the two-step carcinogenesis experiment and normal mice. PMID- 3093739 TI - Gangliosides in human and monkey lenses. AB - The amount of gangliosides was determined in normal human lens, cataractous human lens and normal monkey lens. The total gangliosidic sialic acids averaged 176.3 +/- 44.7 (SD) (n = 4) in normal human lenses, and 272.2 +/- 80.6 (n = 14) nmol per gram wet weight in cataractous lenses, respectively; the difference was statistically significant. In monkey lens, the content was 143.8 +/- 32.4 (n = 4) nmol per gram wet weight. The composition of the gangliosides was analyzed by high performance thin-layer chromatography: the components of the a-pathway biosynthesis comprised 78.3% and 70.2%, and those of the b-pathway 13.8% and 20.9%, in the normal and cataractous human lenses, respectively. In the monkey lens, the components of the a-pathway comprised 33.0% and those of the b-pathway were 56.6% of the total gangliosides. Increase in gangliosides was thought to be related with the mechanism underlying formation of cataract. PMID- 3093740 TI - Stimulatory effect of veratridine on lysophosphatidylethanolamine formation in rat brain synaptosomes. AB - [3H]-Arachidonic acid incorporation into phospholipids of synaptosomal lysates prepared from veratridine-treated synaptosomes was examined. Synaptosomal lysates were shown to acylate exogenously added lysophosphatidylcholine, lysophosphatidylinositol, and lysophosphatidylethanolamine, when incubated with [3H]-arachidonic acid, ATP, CoA and MgCl2, yielding the respective phospholipids. Preincubation of synaptosomes with veratridine for 30 sec gave rise to an increase in [3H]-arachidonic acid incorporation into phosphatidylethanolamine, but not phosphatidylcholine nor phosphatidylinositol, indicating that lysophosphatidylethanolamine might be produced by veratridine. This increase of radioactivity in phosphatidylethanolamine caused by veratridine was completely inhibited by 1 microM tetrodotoxin or in calcium-free condition. These observations show that lysophosphatidylethanolamine was formed in a calcium dependent manner and accumulated in synaptosomes treated with veratridine, which may relate to its action on the sodium channel and enhanced calcium influx. PMID- 3093741 TI - Pharmacological studies on the TXA2 synthetase inhibitor (E)-3-[p-(1H-imidazol-1 ylmethyl)phenyl]-2-propenoic acid (OKY-046). AB - The effects of (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoic acid (OKY 046) on thromboxane A2 (TXA2) synthetase in vitro and on experimental animal models of sudden death and cerebral infarction were studied. IC50 values of OKY 046 for the TXA2 synthetase of human, rabbit, dog and guinea pig washed platelets were 0.004, 0.004, 0.26 and 2.4 microM, respectively. OKY-046 at concentrations up to 1 mM, however, did not inhibit prostacyclin (PGI2) synthetase from bovine aorta microsomes or cyclooxygenase and PGE2 isomerase from sheep seminal vesicle microsomes. Similarly, platelet 12-lipoxygenase was not affected by OKY-046. Evidence for a re-direction of arachidonate metabolism from thromboxane synthesis toward PGI2 synthesis was obtained using rat peritoneal cells. Namely, OKY-046 increased PGI2 production accompanied by an inhibition of TXA2 production at a concentration of more than 1 microM. OKY-046 at a dose of 0.1 mg/kg (i.v.) in dogs inhibited the aortic and mesenteric arterial contraction of rabbit induced by the addition of arachidonate to extracorporated blood of the dogs. OKY-046 at a dose of 0.3 mg/kg (i.v.) prevented the arachidonate-induced sudden death and also decreased the incidence of cerebral infarction induced by injection of arachidonate into the internal carotid artery in rabbits. Aspirin also decreased the incidence of cerebral infarction at a dose of 30 mg/kg (i.v.). These results suggest that OKY-046 may be valuable for the treatment of cerebrovascular and cardiovascular diseases associated with vasoconstriction and thrombosis due to TXA2. PMID- 3093742 TI - [Localization of Pseudomonas aeruginosa in lung tissue in patients with diffuse panbronchiolitis using an immunofluorescent antibody technique and immunoperoxidase staining procedure]. PMID- 3093743 TI - The development of Theileria sergenti in the salivary glands of the tick, Haemaphysalis longicornis. PMID- 3093744 TI - Inhibition and enhancement of skin tumors in mice by dimethyl sulfoxide depending on method of application. AB - The role of dimethyl sulfoxide [(DMSO) CAS: 67-68-5] in experimental tumorigenesis was investigated because of conflicting reports in the literature ranging from inhibition to no effect to enhancement. With the use of numbers of skin tumors produced on the back of the mouse following topical applications of carcinogenic agents as the variable and with acetone serving as the control solvent, the following results were obtained: When DMSO was the solvent for benzo[a]pyrene (CAS: 50-32-8) in the single-stage model (C3H mice), tumor numbers doubled. When DMSO was the solvent for 7,12-dimethylbenz[a]anthracene (CAS: 57-97 6) serving as initiator in the two-stage model (CD-1 mice), tumor numbers were unaffected. In the two-stage model, when DMSO was the solvent for the potent promoter phorbol-12-myristate-13-acetate [(PMA) CAS: 16561-29-8] or was applied to skin at the initiation site (the back) before PMA, tumor numbers were reduced to one-third of control. However, when DMSO was applied before PMA to the abdomen, a site remote from initiation, tumor numbers doubled. Enhancement of PMA appears to be unique. Recognition that diverse effects can occur depending on the method of application of DMSO may help to decipher the conflicting literature on its relation to tumorigenesis, could be of value in probing the mechanism of tumor promotion, and might signal further caution in its clinical use. PMID- 3093745 TI - [Long term care in U.S.A]. PMID- 3093747 TI - [Long term care in U.S.A.--home care providers]. PMID- 3093746 TI - [Clinical tests--are they all necessary ones? Tests and medical economics]. PMID- 3093748 TI - [Psychological preparedness of hypertension patients for undergoing outpatient rehabilitative measures]. PMID- 3093749 TI - [Stenocardia. Thromboxane A2 and prostacyclin]. PMID- 3093750 TI - [Clinical evaluation of N-acetylaspartylglutamic acid eyedrops in subacute and chronic atopic conjunctivitis]. AB - Patients with subacute and chronic atopic conjunctivitis who were treated for at least one year with topically applied 2% sodium cromoglycate 4 times daily were switched to N.A.A.G.A. 6% eye drops for 2 months. A statistically significant gain in treatment effect as assessed objectively (+12.25%) and subjectively (+25.90%) was obtained. This effect could be the result of a more effective antiallergic action of N.A.A.G.A. or could be related to a relative tachyphylaxis to sodium cromoglycate. PMID- 3093751 TI - [Radiotherapy in juvenile xanthogranuloma of the iris]. AB - Nevoxanthoendotheliomas (and juvenile xanthogranulomas) are very rare benign skin diseases which occur in infants. An ocular manifestation, mainly in the iris, has been found in approximately. 10% of the cases, The clinical picture is characterized by a recurrent unilateral hemorrhage of the anterior chamber, which is the reason for seeing an ophthalmologist. The clinical diagnosis of juvenile xanthogranuloma is based on the characteristic iris changes - heterochromia, circumscribed vascularized tumor, or diffuse thickening of the iris. Sometimes elevated intraocular pressure is also found. In combination with a mild local steroid, radiotherapy with 300 to 400 cGy should be started immediately in order to prevent a sometimes uncontrollable secondary glaucoma. The good results achieved in 5 of the authors' own cases underline the value of low-dose radiotherapy in this disease: the affected eye was healed in all 5 cases. PMID- 3093752 TI - [Acute chorioretinitis caused by Listeria monocytogenes]. AB - The present paper reports on a case of acute chorioretinitis caused by Listeria monocytogenes in a 16-year-old girl. The inflammatory process was brought to a standstill by antibiotic therapy in combination with systemic cortisone administration. Final visual acuity in the affected eye was 0.8-1.0. PMID- 3093753 TI - [Significance of immune complexes in children with severe hemophilia A in substitution treatment with factor VIII concentrates]. AB - Sera and EDTA-Plasma of patients with severe Haemophilia A were analysed for immune complexes and the hemolytic activity of complement in relation to Factor VIII replacement, in order to confirm or possibly exclude a relationship to allergic reactions. Immune complexes were isolated by PEG precipitation and quantitated. In addition a solid phase ELISA assay was used to detect complement binding complexes. Total hemolytic complement activity of the classical and the alternate pathway was measured in addition to the C3 splitproduct C3d. The results obtained from 12 patients with severe Haemophilia A showed slightly increased immune complex titers, no changes of the immune complex levels during Factor VIII replacement and no alteration of the complement system following the infusions. One patient developed an allergic reaction without evidence of complement activation. PMID- 3093754 TI - [Noninvasive, continuous monitoring of artificial respiration in premature and newborn infants by the constant measurement of respiratory minute volume, oxygen consumption and carbon dioxide release]. AB - A system of instrumentation for the continuous measurement of the respiratory gases during assisted ventilation of neonates and premature infants based upon "breath-by-breath-method" is described. The four respiratory parameters flow (V), ventilation pressure (p), oxygen-concentration and carbon dioxide-concentration are measured. These datas are processed by a computer to generate a continuous display of the respiratory minute volume, the tidal volume, the breath rate, the oxygen consumption and the carbon dioxide production. All parameters are stored and can be displayed or plotted as trends. The flow-measurement is performed using hot-wire-anemometry. The very small flow sensor is adapted directly to the tube. Next to this sensor, the respiratory gas for the analysis of the O2- and CO2- concentration is suctioned off continuously. First clinical experience in mechanically ventilated newborns is characterized. PMID- 3093756 TI - Nonenzymatic glycosylation of lens in diabetic patients. PMID- 3093755 TI - Technical mishaps as easily avoidable causes of treatment failure when using pumps for pulsatile administration of gonadotropin-releasing hormone. AB - A patient (19 years old) with Kallmann's syndrome was treated with gonadotropin releasing hormone (2.5-16 micrograms) administered subcutaneously every 2 h using a portable infusion pump. During 42 weeks of treatment testosterone levels and testicular size did not increase sufficiently although no reasons for this insufficient response were detectable. Therefore the regime of controlling and changing the catheter system was intensified. By this means partial occlusions of the catheter were detected and could be corrected. Afterwards testosterone levels increased immediately and persistently to normal values. PMID- 3093757 TI - [Use of gas mixtures with a high oxygen and CO2 content for normalizing external respiratory function and the blood acid-base state in muscle fatigue]. AB - Use of gas mixtures containing 1% CO2+ +35% O2 and 35% O2 in the air during a passive rest after a high workload led to the neutralization of acid metabolites and recovery of acid-base equilibrium due to a greater oxygen consumption, retention of metabolic CO2 in plasma, and accumulation of endogenous CO2 in body fluids. PMID- 3093758 TI - [Organizational concepts based on the professional image of nursing of the german Nursing Association]. PMID- 3093759 TI - [Requirements for an ADP-assisted communication system in the area of nursing]. PMID- 3093760 TI - [From skeptic to fan. Report on the ADP-seminar in the Essen Educational Center of the German Nursing Association 29-31 May 1986]. PMID- 3093761 TI - ["Sorry, I am on duty". Considerations on the elaboration of a meaningful service schedule]. PMID- 3093762 TI - [Nursing today and tomorrow. Workpaper of the International Council of Nurses]. PMID- 3093763 TI - [My experiences as a diabetes consultant at the Erlangen Internal Medicine Department of the University Hospital]. PMID- 3093764 TI - [Liability of the care giver in non-written physician's orders and prescriptions]. PMID- 3093765 TI - [Burden of proof on the hospital. Nursing measures have to be documented]. PMID- 3093766 TI - [The Hickman catheter]. PMID- 3093767 TI - Natural killer cells expressing the Leu-11 antigen display phagocytic activity for 2-aminoethylisothiouronium bromide hydrobromide- treated sheep red blood cells. AB - Natural killer (NK) cell subpopulations, identified by anti-Leu-7 and/or anti-Leu 11 monoclonal antibodies, have been investigated in immunoelectron microscopy by using a peroxidase-colloidal gold double labeling system. More than 90% of non-E rosetting/non-adherent Leu-11+ cells and approximately 60% of E rosetting Leu-11+ cells displayed phagocytic capacity for 2-aminoethylisothiouronium bromide hydrobromide treated sheep red blood cells, whereas Leu-7+ -Leu-11- cells consistently failed to ingest 2-aminoethylisothiouronium bromide hydrobromide treated sheep red blood cells. The phagocytic activity of Leu-11+ cells was not dependent on the Leu-7 antigen coexpression. Moreover, the NK capability of Leu 11+ cells has been verified. In both E rosetting and non-E rosetting/non-adherent cell populations, Leu-11+ enriched subsets displayed significantly higher NK capability when compared with Leu-11- cells. Previous reports provided evidence for different cytotoxic capability, recombinant human interleukin 2 mediated activation, and ultrastructural features of Leu-11+ cells in comparison to Leu-7+ Leu-11- cell subset. The data from the present investigation indicate that 2 aminoethylisothiouronium bromide hydrobromide treated sheep red blood cells phagocyting NK cells are confined to the Leu-11+ subset and give added strength to different function capabilities of Leu-11+ and Leu-7+-Leu-11- cells. PMID- 3093768 TI - A guide to neonatal parenteral nutrition. PMID- 3093769 TI - Computer in paediatrics. 17. Computer programme for the diagnosis of acid-base disorders. PMID- 3093770 TI - Technique for assessing the response of the respiratory controller to hypoxia and hypercapnia. AB - A technique, suitable for clinical practice, has been developed to measure quantitatively and separately the effects of hypercapnia on the central and peripheral chemoreceptors, and hypoxia on the peripheral chemoreceptors of a human subject. The technique uses a model to account for the dynamics of CO2 transport in the brain and is based on current concepts of the chemoreceptor system and makes a minimum of assumptions. The method was tested in one subject and there was evidence for hysteresis in the response to hypoxia and short-term adaptation in the response to hypercapnia of the chemoreceptor controller. PMID- 3093771 TI - Compliance changes in glutaraldehyde-treated arteries. AB - Glutaraldehyde tanning of carotid arteries was used to develop a model for studying the effects of compliance on arterial graft performance, independent of other graft parameters. Canine carotid segments were filled with dilute phosphate buffered glutaraldehyde (0-0.5%, pH 7.4), maintained at physiological pressure, and then immersed in either saline or 10.0% glutaraldehyde for up to 1 hr. After rinsing with saline, compliance was measured in vitro. All vessels which were immersed in 10% glutaraldehyde exhibited a significant reduction in compliance compared to native artery control [C = 11.8 +/- 1.3 (mean +/- SEM), % radial change/mm Hg X 10(-2), measured at 100 mm Hg], but maximum stiffness (C = 1.1 +/- 0.3) required that the lumen be specifically exposed to at least 0.025% glutaraldehyde in addition to simple immersion of the vessel segment in 10% fixative. Exposing the artery to 0.5% glutaraldehyde internally, without immersion of the entire structure, caused a decrease in compliance similar to that obtained after immersion in 10% glutaraldehyde, with only saline present in the lumen. Matched pairs of stiff and compliant grafts were generated by exposing the lumen to 0.025% glutaraldehyde and immersing the vessels in 10% fixative or saline, respectively. Light and scanning electron microscopy, internal reflection spectroscopy, and measurements of critical surface tension revealed nearly identical wall morphology and lumenal surface chemistry for these matched pairs. Differential tanning of the internal and external surfaces of carotid arteries thus provides a good model of arterial prostheses, wherein a substantial compliance mismatch can be studied without the complicating influences of varying diameter or differing flow surface properties. PMID- 3093772 TI - Indomethacin, dazoxiben and extravascular lung water after Escherichia coli infusion. AB - The effects of selectively inhibiting synthesis of thromboxane A2 (TXA2) with dazoxiben and of all cyclooxygenase products with indomethacin were studied in goats after infusion of 5 X 10(8) live Escherichia coli bacteria/kg. Pulmonary and systemic pressures, cardiac output, and double indicator dilution extravascular lung water (EVLW) were measured at 15-min intervals. EVLW was determined gravimetrically at 6 hr to confirm the final double indicator dilution values. Plasma levels of TXA2 and prostacyclin (PGI2) were measured as their stable metabolites, TXB2 and 6-keto-PGF1 alpha, respectively. Dazoxiben blocked the increase in plasma TXB2, prevented pulmonary hypertension, and attenuated the increase in EVLW after E. coli. Mean gravimetric EVLW was 8.7 ml/kg in the dazoxiben-treated group compared to 11.3 ml/kg in the untreated control group. Indomethacin blocked the increased plasma TXB2 and 6-keto-PGF1 alpha, attenuated pulmonary hypertension, and prevented almost all increases in EVLW. Mean gravimetric EVLW was 8.2 ml/kg after indomethacin. We conclude that in acute bacteremia, the early pulmonary hypertension is mediated largely by TXA2 (however, a second phase of hypertension results from non-cyclooxygenase products), either production of cyclooxygenase products (perhaps PGI2) inhibits part of the action of pulmonary vasoconstrictors, or indomethacin stimulates the production of other vasoconstrictors (such as lipoxygenase products), and indomethacin prevents the accumulation of EVLW by blocking formation of cyclooxygenase products or by other nonspecific actions. PMID- 3093773 TI - The effect of dextrose and amino acids on respiratory function and energy expenditure in morbidly obese patients following gastric bypass surgery. AB - Hypocaloric dextrose administration results in a diminished minute ventilation, metabolic rate, and ventilatory responsivity to hypercapnea and hypoxia which is rapidly reversed by provision of amino acids in individuals of normal weight. This study compared the effects of peripheral intravenous dextrose and amino acid infusion on respiratory parameters and energy expenditure in 25 morbidly obese patients undergoing gastric bypass surgery. On the first postoperative day, respiratory rate increased (P less than 0.01) and tidal volume decreased (P less than 0.001) maintaining minute ventilation at slightly less than preoperative levels but on subsequent days minute ventilation exceeded baseline values (P less than 0.005) primarily by a sustained increased respiratory rate. Oxygen consumption (P less than 0.005), carbon dioxide production (P less than 0.05), and resting energy expenditure (P less than 0.01) all declined 25% from baseline values on the first postoperative day and subsequently reverted to preoperative values. The type of intravenous fluid had no effect on any of these parameters. A significant difference in respiratory quotient (P less than 0.05) was noted between the two intravenous fluid regimens attributable to the oxidation of the dextrose calories. The failure to detect a difference in metabolic rate or to stimulate respiration despite elevation of serum branched chain amino acids (P less than 0.0001) and ketone bodies (P less than 0.0001) with protein infusion does not suggest a role for nutrient manipulation of respiration in the postoperative care of the morbidly obese patient. PMID- 3093774 TI - A new model for hetero-orthotopic heart-lung transplantation in the dog. AB - A method of hetero-orthotopic heart-lung transplantation is described in the dog. The model was developed to study patterns of rejection in the transplanted heart and lung, since the dog will not survive bilateral pneumonectomy and loss of the Hering-Breuer reflex. After removal of the recipient's left lung the donor heart and left lung are explanted en bloc. End-to-end connection is made of both left main bronchi, and the donor aorta is joined end-to-side with the recipient's descending aorta. An atrio-atrial anastomosis is performed between the recipient's left and the donor's right atrium. Four experiments were done to develop the surgical technique and 10 long-term studies were performed to investigate rejection patterns. The average survival rate of these animals was 28.5 +/- 8.3 days, ranging from 5 to 53 days. Causes of death were not due to operative complications. Heterotopic heart-lung transplantation is an uncomplicated surgical method which does not require cardiopulmonary bypass or anticoagulation and allows the investigator to study heart and lung grafts in dogs for long-term periods after surgery. Bronchoscopy, bronchoalveolar lavage, and heart and lung biopsies of both donor and recipient organs can be performed. PMID- 3093775 TI - Radiotherapy for prostate carcinoma. AB - The charts of 96 patients who received radiotherapy at The M. S. Hershey Medical Center for their prostatic carcinoma were reviewed. The 4-year NED (no evidence of disease) survival rates for patients receiving between 6,500 and 7,000 rad of external beam radiation (EBR) were 92, 78, 56, and 50% for stages A, B, C, and D1, respectively. The 4-year NED survival rate for stage B patients was 90% for those receiving approximately 6,500 rad of EBR, 75% for those receiving approximately 7,000 rad of EBR, and 71% for those receiving interstitial implants. Bowel or urinary complications occurred in 27% (21% grade I, 3% grade II, and 3% grade III) of those receiving approximately 6,500 rad of EBR, 40% (25% grade I, 10% grade II, and 5% grade III) of those receiving 7,000 rad of EBR, and 0% of those receiving interstitial implants. The effects of stage, grade, and treatment type on NED survival and complications are discussed. PMID- 3093776 TI - Blood groups and malignant melanoma. AB - The charts of 168 patients with malignant melanoma were reviewed with regard to the incidence of the major blood groups. Blood group A was encountered in 39.9%, Group B in 7.7%, Group AB in 3%, and Group O in 49.4%. Although blood group O had a higher frequency compared to that of the general white population of various series, the difference was not significant. Patients with blood group A had a median survival of 67.7 months whereas patients with blood group O had a median survival of 46.6 months (p = 0.04). The improved survival for blood group A remained significant only in female patients, when the sexes were considered separately. However, group A had an incidence of 24% in early Clark's lesions while that incidence in group O was 9.8%. Female patients had longer median survival (86 months) than male patients (44 months). PMID- 3093777 TI - Enteral and parenteral nutrition in anorectic patients with advanced gastrointestinal cancer. AB - Seventeen patients with advanced, noncurable gastrointestinal cancer with symptoms of anorexia and malnutrition were treated with controlled enteral or total parenteral nutrition over a 3-week period. Eleven patients received enteral and six parenteral nutrition. The nutrition was given with 30-40 kcal/kg b.w. daily. No anticancer treatment was given. Before and after the treatment period, the patients were assessed regarding their nutritional, immunological, and performance status. None of the studied nutritional parameters changed significantly over the 3-week period and there was no clear indication of an improved lymphocyte reactivity. There was a tendency toward improvement in performance status for the patients on enteral nutrition, while the reverse seemed to be true for the parenteral group. It is concluded that nutritional support may halt the progressive malnutrition often seen in patients with cancer and serve as a palliative treatment in selected patients. PMID- 3093778 TI - The use of absorbable monofilament polydioxanone suture in pediatric cardiovascular operations. AB - Growth of suture lines and anastomoses is required for long-term success after the repair of congenital cardiovascular anomalies. Polydioxanone, an absorbable monofilament suture material, has been used in a variety of operations since April, 1983. Twenty-two of the 46 procedures were coarctation repairs. Complete repairs for anomalous pulmonary veins and transposition of the great arteries, as well as Fontan procedures and systemic-pulmonary shunts, have been performed. Angiographic, gross, and microscopic examination showed good healing. There was no anastomotic disruption or aneurysm formation. The results with this absorbable vascular suture have been uniformly encouraging in a follow-up of up to 30 months. PMID- 3093779 TI - Optical intensification of fibres and cell bodies of diaminobenzidine-stained neurons by means of a modified darkfield technique. PMID- 3093780 TI - Systems of coordinates for stereotactic surgery and cerebral cartography: advantages of ventricular systems in monkeys. PMID- 3093781 TI - Instruments and techniques for the stereotactic surgery based on the CA-CP ventricular system of coordinates in monkeys. AB - The most widely used conventional stereotactic method utilizing the Horsley Clarke coordinate system does not allow accurate intracerebral placements. Improving the precision of stereotactic surgery in monkeys has become imperative in neurological research to limit the waste of animals. This problem can be resolved with the use of a stereotactic technique based on ventricular landmarks utilizing "orthogonal teleradiography". The radiological devices and the stereotactic apparatus developed for the use with this technique are described. The apparatus allows the intercommissural plane of the animal to be placed parallel to the rails of the stereotactic frame by means of a head rotation around the ear bars. In addition, the technique uses metric reticles to make the interchange between ventricular and mechanical coordinates possible. The ventriculographic and stereotactic procedures are also described. PMID- 3093782 TI - Nutrient intake in critically ill patients: too many or too few calories? AB - We studied the relationship of caloric needs and total caloric intake in a series of 61 critically ill patients in an intensive care unit. All patients were receiving only central parenteral nutrition. On the basis of the ratio of total caloric intake to resting energy expenditure (REE), the nonprotein respiratory quotient (npRQ), and, when appropriate, Lusk's table for analysis of the oxidation of mixtures of carbohydrate and fat, the patients could be categorized into three groups. The group with inadequate caloric intake had a ratio of total calories to REE of less than 1.0. The group with net lipolysis had a ratio of caloric intake to REE of 1.0 or more and npRQ values of less than 1.0. The group with net lipogenesis had a ratio of caloric intake to REE of 1.0 or more and either npRQ values or equivalent npRQ values of 1.0 or more. Equivalent npRQ values in patients who were receiving amino acids, dextrose, and lipids were determined by using Lusk's table and the percentage of total caloric intake as fat. PMID- 3093783 TI - DRGs and disease staging for reimbursing Medicare patients. AB - Beginning October 1, 1983, Medicare began reimbursing many hospitals on the basis of a set of fixed fees tied to Diagnosis-Related Groups (DRGs). Using 1979-1981 Maryland data for Medicare patients, this paper compares the DRG system with the Disease Staging patient classification system in terms of structure, explanation of resource consumption (length of stay) of hospital patients, and impact on reimbursement by type of hospital. The two systems are conceptually and empirically different in classifying patients. Further, Disease Staging and DRGs perform similarly in explaining length-of-stay variation among Maryland patients. However, the two systems generate substantially different reimbursements by type of hospital. Surprisingly, large hospitals (including urban, not-for-profit, teaching hospitals) fare better under a DRG-based reimbursement system than under Disease Staging, a severity-of-illness system that excludes procedures as a basis of classification. These results imply that reimbursement policy based on Disease Staging would create disincentives to perform surgery compared with the current DRGs. PMID- 3093784 TI - Differences in hospital discharge rates. A community-based analysis. PMID- 3093785 TI - Use of medical care in the Rand Health Insurance Experiment. Diagnosis- and service-specific analyses in a randomized controlled trial. PMID- 3093786 TI - [Demyelinating polyneuropathy associated with Waldenstroms macroglobulinemia with anti-myelin antibodies]. PMID- 3093787 TI - [Biological properties of Pseudomonas isolated from food]. PMID- 3093788 TI - [Intracutaneous skin suture with a resorbable synthetic monofilament suture]. AB - We report about our good experience with a monofile, synthetic, absorbable Polydioxanone thread used for skin suture in an intracutaneous technique, after we performed more than 1,500 sutures of 7 to 30 cm length in patients of any age. We consider the suture to be suitable for children to achieve a cosmetically fine scare without a subsequent necessity to pull out the thread. The breaking strength, the absorbtion rate and the loss of inflammatory reaction is so satisfactory that we could not see any disadvantage by using this absorbable, synthetic thread for skin closure. Especially there was no disturbance in wound healing. In contrast, because of the secure and undisturbed wound-edge adaptation a non-irritant, firm, and hairline-like scar could be achieved. The time to carry out the suture is no longer than for other techniques. PMID- 3093790 TI - The CO2 laser in plastic surgery. PMID- 3093789 TI - [Closure of median sternotomy with resorbable synthetic sutures]. AB - To date, the refixation of the bone halves after median sternotomy is accomplished with wire, steel bands or thick, not absorbable plastic threads. As the first, we used absorbable synthetic strings in 25 patients. During the absorbtion the development of a very strong bone scar was possible, because the absorbtion lasted very long. The refixation of the sternum in cases of aseptic instability was even possible. So we think to have found another range of application for absorbable synthetic material which recently has been used more and more in several parts of operative medicine, even in hard burdened connective tissue. PMID- 3093791 TI - Latest treatment in dentistry by means of the CO2 laser beam. PMID- 3093792 TI - Mid-infrared fiber optics. AB - Fiber optics for carbon dioxide laser surgery have been in developmental research for the past ten years. An up-to-date presentation of infrared fiber optics as they pertain to laser surgery is presented. Optical properties such as intrinsic and extrinsic electronic absorption, multiphonon absorption, and scatter mechanisms are discussed. Real-world considerations for materials selection and fabrication techniques for both crystalline and glassy fiber optics give the reader a perspective regarding the stage of development of these devices. Data are presented indicating transmission ranges and absorption coefficients for both bulk materials and fabricated fiber optics. The conclusions are drawn based on the needs of the clinician as they relate to the degree of existing technology. PMID- 3093793 TI - Rapid and high-yield purification of porcine heart tissue-type plasminogen activator by heparin-sepharose choromatography. AB - A rapid and high-yield procedure for the purification of single polypeptide tissue-type plasminogen activator (t-PA) from porcine heart tissue has been developed. Delipidated heart tissue was extracted with 0.45 M potassium acetate. The extract was fractionated with ammonium sulfate and purified by a combination of affinity chromatography on heparin-Sepharose CL-6B and gel filtration on Toyopearl HW-55S. The final product had a specific activity of 220,000 IU/mg protein and gave a single protein band (apparent molecular weight; 67,000) in SDS polyacrylamide gels in the presence or absence of a reducing agent. The increase in specific activity was 3,200-fold, most of which was achieved in the step of heparin-Sepharose chromatography. The yield calculated from the active ammonium sulfate precipitate was about 90% and 500 micrograms or more of the purified enzyme was obtained from 1 kg wet tissue. This procedure may also be useful for the large-scale production of highly purified t-PA from other tissues or tissue culture cells. PMID- 3093794 TI - Neuropeptide-specific peptidases: does brain contain a specific TRH-degrading enzyme? AB - The particulate fraction of brain homogenates contains an enzyme that cleaves the pyroglutamyl-histidyl bond of thyrotropin-releasing hormone (TRH) but is clearly distinct from the more widely distributed pyroglutamyl peptidase (EC 3.4.19.3). This particulate enzyme is highly localized to brain where it is found on synaptosomal membranes. It exhibits an unusual degree of substrate specificity. For example, it does not cleave the pyroglutamyl-histidyl bond of luteinizing hormone-releasing hormone (LHRH) or the pyroglutamyl histidyl bond of the chromogenic substrate pyroglutamyl-histidyl-2-naphthylamide. Evidence is reviewed supporting the possibility that this enzyme, first detected in serum and originally referred to as "thyroliberinase", may be the first neuropeptide specific peptidase to be characterized. PMID- 3093795 TI - Progesterone induction of phospholipid methylation and arachidonic acid turnover during the first meiotic division in amphibian oocytes. AB - Progesterone is the physiological stimulus that acts at the amphibian oocyte plasma membrane to induce the meiotic divisions. Rana oocytes were preincubated with [3H]-arachidonic acid, [3H]-methionine and/or [14C]choline. Total and plasma membrane phospholipids were monitored during the first 2 h after induction with progesterone. A transient increase in methylation of phosphatidylethanolamine during the first 10 minutes coincided with an increased Ca2+ efflux and was followed by increased arachidonic acid incorporation into phosphatidylcholine during a period of increasing membrane conductance. The labeled phospholipids disappeared sequentially 5-90 min after the hormone stimulus, suggesting that activation of phospholipases A2 and/or C occur as part of a cascade of membrane events. PMID- 3093796 TI - The effect of feeding fish oils, vegetable oils and clofibrate on the ketogenesis from long chain fatty acids in hepatocytes. AB - Groups of rats were fed diets containing 25% fish oil (FO), 25% soybean oil, 25% partially hydrogenated fish oil (PHFO), 25% partially hydrogenated soybean oil (PHSO), 25% partially hydrogenated coconut oil or 0.3% clofibrate for 3 wk. After the animals were fasted for 24 hr, hepatocytes were isolated and ketogenesis from added palmitate, linoleate cis and trans, arachidonate and docosahexaenoate was measured. Ketogenesis after oil feeding was significantly stimulated (two- to threefold) only in cells from the PHFO- and PHSO-fed rats. The stimulation was most apparent with the long chain unsaturated fatty acids as substrates. These fatty acids were relatively poor ketone body precursors in control hepatocytes. Essential fatty acid deficiency did not seem to be the reason for this stimulation. Clofibrate also stimulated ketogenesis significantly (1.5- to 3 fold). The degree of stimulation increased with chain length and degree of unsaturation of the substrate. The activity of the enzyme 2,4-dienoyl-CoA reductase was also studied in the same groups. Its activity was stimulated about fourfold in the clofibrate-treated rats and to a lesser extent by the PHFO, PHSO and FO diets. The activity showed no correlation with the content of unsaturated fatty acids in the diet or their oxidation in isolated hepatocytes. The 2,4 dienoyl-CoA reductase, therefore, does not seem to be a regulatory enzyme in the metabolism of dietary polyunsaturated fatty acids. It is concluded that an induction of the peroxisomal beta-oxidation system most likely is involved in the reported increases in ketogenesis from very long chain polyunsaturated fatty acids. PMID- 3093797 TI - Gradual recovery of lactotroph responsiveness to dynamic stimulation following surgical removal of prolactinomas: long-term follow-up studies. AB - Prolactin-secreting pituitary adenomas were selectively removed through a transsphenoidal approach from 120 women. Basal serum PRL levels (measured one to six months after surgery) were normal in 96 patients and decreased appreciably but not to normal in the remaining 24 patients. Dynamics of PRL secretion were studied at three to four months in 81 patients who had normal basal PRL level. Two different patterns of response to provocative stimuli were noted in these patients. In one group (group I, n = 65), patients had greater than 100% rise in serum PRL following TRH or perphenazine (Pz) administration. However, when analyzed as a group, the mean +/- SEM incremental responses (delta PRL) to TRH and Pz in these patients (29.9 +/- 1.9, 20.4 +/- 1.5 ng/mL) were significantly less (P less than 0.005 and P less than 0.001) than those of normal women (38.8 +/- 5, 33 +/- 5 ng/mL, respectively). Nineteen of these patients were restudied 12 to 72 months after surgery. The responses to provocative stimulation at that time were improved and similar to normal women. In contrast, in the second group (n = 16) of patients (group II), the responses to stimulation with the same agents were blunted or absent and remained so during subsequent studies. Recurrence of the hyperprolactinemia was noted in 11 of the 16 patients in group II and in only two of 65 patients in group I. The daily serum PRL levels in the immediate postoperative period were higher in patients from group II than those from group I. We conclude that transsphenoidal surgery is an optimal form of therapy for patients with PRL-secreting adenomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093799 TI - Production and purification of mouse immune interferon. PMID- 3093798 TI - The aqueous humor of rabbit contains high concentrations of pyrroline-5 carboxylate. AB - Accumulating evidence suggests that the interconversion of proline and pyrroline 5-carboxylate (P5C) transfers oxidizing or reducing potential within or between cells. We report here that rabbit aqueous humor contains P5C at a concentration at least 20 times that found in rabbit plasma or in biologic fluids from other animals, and, in isolated lens, P5C stimulates the activity of the pentose phosphate shunt. However, aqueous humor in other species contains P5C in the same range of concentrations as their respective plasma. The high P5C concentration in rabbit aqueous humor may be due to comparatively low levels of P5C reductase activity in ocular tissues, especially the cornea. The levels in lens epithelium, though lower in the rabbit, nevertheless could mediate the transfer of oxidizing potential from P5C and stimulate the pentose-phosphate shunt. These results suggest that the eye may serve as a convenient model for the study of proline and P5C-related transfer of reducing or oxidizing potential between tissues. PMID- 3093800 TI - Purification of natural human immune interferon induced by A-23187 and mezerein. PMID- 3093801 TI - Nickel chelate chromatography of human immune interferon. PMID- 3093802 TI - Purification of recombinant human immune interferon. PMID- 3093803 TI - Radiation inactivation and target size analysis of interferons. PMID- 3093805 TI - Radiolabeling of human immune interferon with 125I-labeled Bolton-Hunter reagent. PMID- 3093804 TI - Radiolabeling of human leukocyte and immune interferons with 125I and lactoperoxidase. PMID- 3093806 TI - In vivo radiolabeling of human IFN-beta. PMID- 3093807 TI - Phosphorylation of human immune interferon (IFN-gamma). PMID- 3093808 TI - Yeast vectors for production of interferon. PMID- 3093809 TI - Cloning, expression, and purification of rat IFN-gamma. PMID- 3093810 TI - Induction of human interferon gamma with phorbol esters and phytohemagglutinin. PMID- 3093811 TI - Production and partial purification of human immune interferon. PMID- 3093812 TI - A sandwich radioimmunoassay for human IFN-gamma. PMID- 3093813 TI - Induction of human immune interferon with ionophores. PMID- 3093814 TI - Production of human immune interferon with normal human leukocytes by the inducers A-23187 and mezerein. PMID- 3093815 TI - Large-scale production and recovery of human immune interferon. PMID- 3093816 TI - Large-scale production, concentration, and partial purification of human immune interferon. PMID- 3093817 TI - Production and partial purification of human immune interferon induced with concanavalin A, staphylococcal enterotoxin A, and OK-432. PMID- 3093818 TI - Induction of human immune interferon from peripheral blood mononuclear cells induced with combinations of T cell mitogens. PMID- 3093819 TI - Preparation and partial purification of human interferon delta. PMID- 3093820 TI - Characterization of DNA uptake by the cyanobacterium Anacystis nidulans. AB - The binding and uptake of nick-translated 32P-labeled pBR322 by Anacystis nidulans 6301 have been characterized. Both processes were considerably enhanced in permeaplasts compared to cells. The breakdown of labeled DNA was not correlated with binding or uptake by permeaplasts or cells. Uptake of DNA by permeaplasts was unaffected by: Mg2+ or Ca2+, light, or inhibitors of photophosphorylation such as valinomycin or gramicidin D in the presence or absence of NH4Cl. ATP at 2.5-10 mM inhibited both binding and uptake of labeled DNA by permeaplasts of A. nidulans whereas the ATP analog adenyl-5-yl imido diphosphate was non-inhibitory in the same concentration range. In contrast to transformation of A. nidulans 6301 cells to ampicillin-resistance by pBR322, transformation to kanamycin-resistance by the plasmid pHUB4 was considerably enhanced in the dark. The transformation efficiency for permeaplasts by the plasmid pCH1 was 59% and 8% in the dark and light, respectively, whereas transformation of permeaplasts by pBR322 at an efficiency of 16% was absolutely light-dependent. PMID- 3093821 TI - Cloning of Clostridium acetobutylicum genes and their expression in Escherichia coli and Bacillus subtilis. AB - DNA from Clostridium acetobutylicum ABKn8 was partially digested with Sau3A and the fragments obtained were inserted into the unique BamHI site of the cloning vector pHV33. The recombinant plasmids were used to transform Escherichia coli HB101 with selection for ampicillin resistance. A collection of ampicillin resistant, tetracycline-sensitive clones representative of the Clostridium acetobutylicum genome was made. The clones were shown to carry recombinant plasmids each containing an insert of 2 to 16 kb in size. Several of them complemented the HB101 proA2 or leuB6 auxotrophic mutations. The cloned sequences were shown by Southern blot hybridization to be homologous to the corresponding ABKn8 DNA fragments. PMID- 3093822 TI - The Hfr status of Pseudomonas aeruginosa is stabilized by integrative suppression. AB - A temperature-sensitive mutant (dna-11) with the phenotype of a mutant defective in the initiation of DNA replication, was isolated from an Hfr-like FP2 donor of Pseudomonas aeruginosa. Reversion of its temperature-sensitive character was achieved by integrative suppression rather than by backmutation or an additional suppressor mutation. The dna-11 mutant proved to be helpful in stabilizing the Hfr status of the original host. PMID- 3093824 TI - Uptake and release of adenosine by cultured rat aortic smooth muscle. AB - We wanted to determine whether CO2, H+ and K+ affect the adenosine metabolism of vascular smooth muscle in a way that could account for the effects of these substances on vascular reactivity and their ability to modulate adenosine-induced vascular relaxation. Accordingly, 1-week-old cultures of rat aortic smooth muscle were incubated in phosphate-buffered saline with various [K+]'s and pH's and aerated in an incubation chamber with gases containing various proportions of CO2. Uptake was measured as 14C incorporation into cellular constituents during exposure to 2 microM [14C]adenosine. Release was measured as net extracellular adenosine accumulation. Uptake of adenosine was not significantly affected by any of the experimental maneuvers, except that it was greatly attenuated by dipyridamole (10(-5) and 10(-4) M) and transiently enhanced by the low CO2 levels. Adenosine release, however, was depressed by lowering atmospheric CO2 (0% vs 5%) and also by normocapnic acidosis (pH 6.8 vs pH 7.4). We conclude that vascular smooth muscle in culture releases adenosine at a rate that might have vasoactive significance in vivo. Furthermore, some of the vascular actions of CO2 and H+, but not those of K+, may be partially explained by their effects on vascular smooth muscle's adenosine metabolism. PMID- 3093825 TI - Carbon dioxide inhalation therapy for anxiety: effectiveness due to increased prostacyclin and decreased thromboxane biosynthesis? Re-evaluation of a neglected technique. AB - CO2 inhalation has been used for many years in the treatment of various psychiatric and medical disorders and different rationales for its effect have been offered. Since it has been recently found that CO2 inhibits thromboxane biosynthesis and raises levels of prostacyclin, a new rationale for the effect of CO2 inhalation, based on its inhibition of thromboxane biosynthesis, is offered. PMID- 3093823 TI - Integration of vector-containing Bacillus subtilis chromosomal DNA by a Campbell like mechanism. AB - Using plasmid pHV60, which contains a chloramphenicol resistance (Cmr) gene that is expressed in Bacillus subtilis, a set of transformation-deficient strains of B. subtilis was isolated by insertional mutagenesis. When chromosomal DNA from these mutants was used to transform a transformation-proficient B. subtilis strain, almost all of the Cmr transformants had the mutant phenotype as expected. However, with a frequency of approximately 3 X 10(-4) atypical transformants with the wild-type phenotype were produced. Data concerning amplification of the DNA containing the Cmr marker and duplication of DNA sequences are presented that suggest that these atypical transformants are the result of a Campbell-like integration of the chromosomal DNA containing the integrated plasmid. Transductional mapping showed that in the atypical transformants the vector containing DNA had a strong tendency to integrate at sites adjacent to the original site of integration, although integration at sites elsewhere on the chromosome was also observed. The production of atypical transformants is explained on the basis of integration of chromosomal DNA by a Campbell-like mechanism. Circularization of vector-containing chromosomal DNA is thought to occur through joining of the extremities of single-stranded DNA molecules by fortuitous base pairing with an independently entered single-stranded DNA molecule. PMID- 3093826 TI - Are some major in vivo effects of gold related to microenvironments of decreased selenium? AB - Gold interacts with selenium in vivo, and the normal distribution of selenium among tissues and subcellular compartments changes. Literature evidence shows that many of the effects of gold compounds on the polymorphonuclear neutrophil, macrophage, and lymphocyte cellular components of the immune system are similar to effects observed in these cellular components in selenium-deficient animals. Affected by these two metals are immune functions related to phagocytic cell migration, phagocytosis, microbial killing, lymphocyte mitogenesis/DNA synthesis, arachidonic acid metabolism/prostaglandin synthesis, and immunoglobulin production. The interaction of gold with selenium in vivo may be responsible for some of the multiparameter-based actions of gold compounds used in the treatment of inflammatory diseases such as rheumatoid arthritis. One mechanism by which gold exerts its clinical effects may be related to its interaction with selenium to produce, in specific microenvironments, decreased levels of this essential trace element. PMID- 3093827 TI - The effect of maintenance cimetidine therapy on the medical, social and economic aspects of patients with chronic gastric ulcers. A placebo-controlled prospective study. AB - We studied the effect of cimetidine maintenance therapy on the socioeconomic life of patients with gastric ulcers in the year after healing and the extent to which treatment was cost-effective. One hundred and seventy patients with a healed ulcer were studied for periods of up to one year after healing; 116 patients completed one year of observation. A double-blind randomized prospective study was performed that compared cimetidine (400 mg at night) with placebo. Analysis was performed on the intention-to-treat principle. The treated group showed benefit over the placebo group; major or minor symptoms were experienced on fewer days, and more months were symptom-free. Male patients were wakened with ulcer pain on fewer nights, led a more normal social life, and had less ulcer-related sick-leave; female patients had less total sick leave. The proven ulcer recurrence rate was lower in the treated group. Fewer endoscopies were performed in this group and the resultant cost saving was equivalent to the cost expenditure on cimetidine treatment. A modest saving in wages was afforded treated patients in the workforce, due to the reduction in sick leave. The principal benefit of cimetidine treatment appeared to be the lessening of the pain and discomfort and, hence, the distress and anxiety that was associated with ulcer disease. The cost-saving due to the reduced number of endoscopies compensated for the cost-expenditure of the cimetidine treatment. PMID- 3093828 TI - Chronic zinc deficiency and listeriosis in rats: acquired cellular resistance and response to vaccination. AB - The functional significance of zinc deficiency on primary and secondary host responses to infection with a facultative intracellular pathogen was studied in specific pathogen free rats. Groups of female rats fed either a low zinc or normal diet for 8 or 10 weeks were infected with Listeria monocytogenes five days prior to sacrifice. Zinc-deficient rats demonstrated thymic atrophy, reduced delayed hypersensitivity responses to listeria antigen, and impaired lymphocyte response of spleen cells to phytohemagglutinin, but not to Concanavalin A. Separate groups of zinc-deficient or control rats were vaccinated with viable L. monocytogenes 10 days prior to respiratory challenge. Vaccination resulted in successful control of bacteria in both dietary groups. PMID- 3093829 TI - [Suppression of chloroquine resistance in Plasmodium berghei by using a microsomal monooxygenase inhibitor]. PMID- 3093830 TI - Adult day care: substitute or supplement? AB - In 1972 there were fewer than 10 nonpsychiatric adult day care centers in the United States; by late 1982 there were 1,000 or more. This development of programs as an alternative to nursing home and hospital care of impaired adults has been haphazard. Complications from surveys, field visits, and regulatory agencies reveal a lack of elements for systematic evaluation of the real costs and benefits. Future policies must also recognize that adult day care has become a new service without significantly diminishing institutional use. PMID- 3093831 TI - Na-Ca exchange in renal tubular basolateral membranes. AB - We investigated the Na-dependent Ca transport in purified bovine luminal and basolateral renal tubular membranes. Na-dependent Ca uptake was observed in basolateral but not in luminal kidney tubular membranes. 45Ca uptake in basolateral membrane vesicles loaded with Na and suspended in K buffer was significantly greater than that observed in vesicles loaded with Na and suspended in Na buffer. The Na ionophore ETH-227 inhibited Na-dependent Ca uptake indicating that the Ca uptake was dependent on Na gradient. The Ca taken up in the presence of Na gradient could be released by the Ca ionophore A-23187 suggesting that Ca was accumulated inside the vesicles. In vesicles loaded with 45Ca, addition of Na to the media promoted Ca efflux. Methyl triphenylphosponium uptake and Ca uptake were significantly higher in the presence of a Na gradient as compared to those observed in the presence of other monovalent cation gradients, indicating the specificity for Na gradient and arguing against a calcium-activated sodium conductance pathway. The Na-dependent Ca uptake varied with intravesicular Na concentration with an apparent Km of 20-40 mM. The Km for Ca of the Na-dependent Ca uptake was 50 microM and the Vmax was 0.2 nmol/mg protein/min. The Na-dependent Ca uptake was inhibited by LaCl3, tetracaine and verapamil, unaffected by quinidine and amiloride, and slightly stimulated by chymotrypsin. These data demonstrate that the Na-dependent Ca transport by renal basolateral membranes is mediated by a Na-Ca exchange system and not by a calcium activated sodium conductance pathway. PMID- 3093833 TI - Group-A, -B hemolytic Streptococcus skin infections in a meat-packing plant- Oregon. PMID- 3093832 TI - Congenital syphilis--United States, 1983-1985. PMID- 3093834 TI - North Carolina drownings, 1980-1984. PMID- 3093835 TI - Use of smokeless tobacco--Wisconsin. PMID- 3093836 TI - Update: Aedes albopictus infestation--United States. PMID- 3093837 TI - Years of life lost from cardiovascular disease. PMID- 3093838 TI - Acquired immunodeficiency syndrome (AIDS) among blacks and Hispanics--United States. PMID- 3093839 TI - Patterns of alcohol consumption and alcohol-related morbidity and mortality. PMID- 3093840 TI - Trichinosis surveillance, 1984. PMID- 3093841 TI - The National Occupational Health Survey of Mining. PMID- 3093842 TI - Trends in the incidence of endometrial and ovarian cancers. PMID- 3093843 TI - Ectopic pregnancy in the United States, 1970-1983. PMID- 3093844 TI - Abortion surveillance: preliminary analysis--United States, 1982-1983. PMID- 3093845 TI - [Kinetic model of a multienzyme system of blood prostanoid synthesis. I. Mechanism of stabilization of thromboxane and prostacyclin levels]. AB - A kinetic scheme of the prostacyclin-thromboxane system has been evolved on the basis of the authors experimental data and the results described elsewhere. The kinetic behavior of the model has been analysed with the aid of computer technology by varying the following parameters: phospholipase activities, free arachidonic acid exchange rates between platelets and endothelium, PGH-synthetase biosynthesis rates, velocities of arachidonic acid pathways other than the cyclooxygenase ones. It has been demonstrated that the biological system is capable of sustaining prostacyclin and thromboxane concentrations at steady fixed levels within a wide range of kinetic parameters. PMID- 3093847 TI - IgG subclasses in parasitic infestations. PMID- 3093846 TI - [Kinetic model of a multienzyme system of blood prostanoid synthesis. II. Dynamic responses to pharmacological agents--inhibitors of prostaglandin H synthetases]. AB - The dynamic replies of the multienzyme system of blood prostanoid synthesis to the introduction of an irreversible inhibitor of prostaglandin H synthetase (PGH synthetase) have been analysed by using kinetic modelling. The alterations of arachidonic acid and PGH synthetase concentrations in platelets and endothelium and the concentrations of thromboxane and prostacyclin have been demonstrated. Particularities of kinetic behaviour of the system probably providing the therapeutic effect of non-steroidal anti-inflammatory drugs have been shown. Namely, the kinetic wave of free arachidonic acid and prostacyclin concentration with respect to thromboxane concentration appears after introduction of the drugs. PMID- 3093848 TI - IgG subclasses in respiratory disorders: cystic fibrosis. PMID- 3093849 TI - IgG subclass changes in response to replacement therapy with clotting factor VIII. PMID- 3093850 TI - IgA subclasses. PMID- 3093851 TI - Gm and Km allotypes, immune response and disease susceptibility. PMID- 3093852 TI - Methods of detecting IgG subclass proteins and antibodies. PMID- 3093853 TI - Resolution of pancreatic pseudocysts: when should we wait? PMID- 3093854 TI - Hypersensitivity of Drosophila mei-41 mutants to hydroxyurea is associated with reduced mitotic chromosome stability. AB - 6 mutant alleles of the mei-41 locus in Drosophila melanogaster are shown to cause hypersensitivity to hydroxyurea in larvae. The strength of that sensitivity is directly correlated with the influence of the mutant alleles on meiosis in that: alleles exhibiting a strong meiotic effect (mei-41D2, mei-41D5, mei-41D7) are highly sensitive; alleles with negligible meiotic effects (mei-41(104)D1, mei 41(104)D2) are moderately sensitive and an allele which expresses meiotic effects only under restricted conditions (mei-41D9) has an intermediate sensitivity. This sensitivity is not a general feature of strong postreplication repair-deficient mutants, because mutants with that phenotype from other loci do not exhibit sensitivity (mus(2)205A1, mus(3)302D1, mus(3)310D1). The observed lethality is not due to hypersensitivity of DNA synthesis in mei-41 larvae to hydroxyurea as assayed by tritiated thymidine incorporation. Lethality is, however, potentially attributable to an abnormal enhancement of chromosomal aberrations by hydroxyurea in mutant mei-41 larvae. Both in vivo and in vitro exposure of neuroblast cells to hydroxyurea results in an increase in 3 types of aberrations which is several fold higher in mei-41 tissue. Since hydroxyurea disrupts DNA synthesis, these results further implicate the mei-41 locus in DNA metabolism and provide an additional tool for an elucidation of its function. The possible existence of additional genes of this nature is suggested by a more modest sensitivity to hydroxyurea which has been detected in two stocks carrying mutagen-sensitive alleles of alternate genes. PMID- 3093855 TI - Proliferation-dependent reduction of sister-chromatid exchange frequency induced by mitomycin C in human lymphoblastoid cells and its suppression by inhibitors of DNA replication. AB - A high frequency of sister-chromatid exchange (SCE) induced in cells of a human lymphoblastoid cell line, NL3, by 2-h treatment with 1 microM mitomycin C (MMC) was maintained after holding the treated cells in a nonproliferating state for 48 h before cells were transferred into the BrdUrd-containing medium for SCE assay. The same was observed in cells treated with 4-nitroquinoline 1-oxide (4NQO) or ethyl methanesulfonate (EMS). In contrast, when MMC-treated cells were transferred into a growth medium and allowed to proliferate for various periods of time before SCE assay, MMC-induced SCE frequency decreased with time and reached near control level after 48 h. The reduction in SCE was also observed in 4NQO-treated cells, though to a lesser extent, but not in EMS-treated cells. When hydroxyurea or 1-beta-D-arabinofuranosylcytosine was given as a post-MMC treatment during this recovery process, such a reduction of SCE frequency was suppressed and the extent of the suppression appears to be roughly parallel to their ability to inhibit DNA replication. Cycloheximide and 5-azacytidine also exerted a similar inhibitory effect on the reduction of SCE. Benzamide and caffeine had no appreciable effect. Our results indicate that the SCE-forming lesions induced by MMC can be eliminated only in proliferating cells, probably during DNA replication. PMID- 3093856 TI - Genetic analysis of mitomycin-C-sensitive mutants of a Chinese hamster ovary cell line. AB - 5 mutants of a Chinese hamster ovary (CHO) cell line, which exhibit similar levels of sensitivity to killing by mitomycin C, have been analysed genetically to determine whether they represent one or more genetic complementation groups. Hybrids were constructed by fusing cells carrying either the neo or the Ecogpt marker and selecting in medium containing G418 and mycophenolic acid. Selectable markers were introduced into the cells by DNA transfection using pSV5-neo or pSV5 gpt, which represents a quick and convenient method for generating resistant derivatives. Hybrids generated by crosses between any one mutant and the parental cell line exhibited near wild-type resistance to mitomycin C, indicating that the mutants are phenotypically recessive. Self-cross hybrids for all 5 mutants had D37 values for killing by mitomycin C of between 20 and 30 ng/ml. The values obtained for crosses between different mutants were 60-105 ng/ml, with the exception of 1 pairing which gave a value of 33 ng/ml. These results indicate that that the mutants represent at least 4 different genetic complementation groups, suggesting that cellular resistance to mitomycin C is mediated via a number of different mechanisms. PMID- 3093857 TI - Suppression of 7,12-dimethylbenz[a]anthracene-induced chromosome aberrations in rat bone marrow cells by vegetable juices. AB - A study was made of the in vivo effects of various vegetable juices on 7,12 dimethylbenz[a]anthracene (DMBA)-induced chromosome aberrations (CA) in rat bone marrow cells. DMBA-induced CA consisted mainly of gaps and breaks. Exchanges were observed infrequently. Depending on the progressive severity of their chromosome damage, cells were classified into 4 categories: cells with gaps only, cells with breaks, cells with exchanges, and cells with multiple CA (more than 10 aberrations). Multiple Ca and the number of aberrations per cell, reflecting the severity of damage within a cell, were significantly suppressed by most vegetable juices investigated. The effect of fresh or boiled juices from 10 vegetables on the incidence of DMBA-induced aberrant metaphase cells (not including cells with gaps) revealed significant suppression of the incidence by fresh or boiled juice from onion, burdock, egg plant, cabbage and welsh onion. There was no difference between the effect of fresh juice or boiled juice except in the pumpkin. Fresh pumpkin juice, conversely, enhanced the incidence of aberrant cells, while boiled pumpkin juice significantly suppressed it. The present results may suggest that some vegetables, such as onion, suppress chemically induced cancer. Glutathione also suppressed DMBA-induced CA; it is, of course, well known that SH compounds analogous to GSH are plentiful in onion and welsh onion. PMID- 3093858 TI - Suppressive effects of coffee on the SOS responses induced by UV and chemical mutagens. AB - SOS-inducing activity of UV or chemical mutagens (AF-2, 4NQO and MNNG) was strongly suppressed by instant coffee in Salmonella typhimurium TA1535/pSK1002. As decaffeinated instant coffee showed a similarly strong suppressive effect, it would seem that caffeine, a known inhibitor of SOS responses, is not responsible for the effect observed. The suppression was also shown by freshly brewed coffee extracts. However, the suppression was absent in green coffee-bean extracts. These results suggest that coffee contains some substance(s) which, apart from caffeine, suppresses SOS-inducing activity of UV or chemical mutagens and that the suppressive substance(s) are produced by roasting coffee beans. PMID- 3093859 TI - Interferon-gamma suppresses the growth of Toxoplasma gondii in human fibroblasts through starvation for tryptophan. AB - The effect of human recombinant interferon-gamma (IFN-gamma) on Toxoplasma gondii in cultured human fibroblasts is predominantly parasitostatic. This effect is dependent upon the induction in the host cell of a potent indoleamine 2,3 dioxygenase that converts tryptophan to N-formylkynurenine. This product is, in turn, degraded to kynurenine by a formamidase. Within 24 h of treatment with IFN gamma most of the tryptophan originally present in the medium is converted to these products together with some minor metabolites. When added to the medium of infected cultures at concentrations equimolar to the tryptophan content, neither N-formylkynurenine nor kynurenine suppresses the growth of T. gondii, although at higher concentrations they are effective. The medium of uninfected cultures treated with IFN-gamma for 24 h has no effect on the growth of T. gondii, when transferred to fresh cultures provided that the residual IFN-gamma is first removed by ultrafiltration or neutralized with a specific monoclonal antibody. Thus minor metabolites produced from tryptophan in response to IFN-gamma and excreted into the medium are not parasitostatic. When cultures treated with IFN gamma for 24 h are incubated with medium that contains [3H]tryptophan, the radioactive amino acid is converted to N-formylkynurenine and kynurenine as rapidly as it enters the cell. This degradation not only results in a very low intracellular concentration of tryptophan but also produces intracellular concentrations of tryptophan metabolites that are significantly higher than the tryptophan concentration in control cells. However, it is unlikely that either metabolite reaches intracellular concentrations that are sufficient to suppress the growth of the parasite. The parasitostatic effect of IFN-gamma is most likely to result from the starvation of T. gondii for tryptophan. PMID- 3093860 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 40-1986. A 28-year-old Cambodian immigrant woman with recent fever and abdominal distention. PMID- 3093861 TI - Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. AB - Acetylcholine is believed to dilate normal blood vessels by promoting the release of a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). By contrast, if the endothelium is removed experimentally, acetylcholine constricts blood vessels. We tested the hypothesis that muscarinic cholinergic vasodilation is impaired in coronary atherosclerosis. Graded concentrations of acetylcholine and, for comparison, the nonendothelial-dependent vasodilator nitroglycerin were infused into the left anterior descending artery of eight patients with advanced coronary stenoses (greater than 50 percent narrowing), four subjects with angiographically normal coronary arteries, and six patients with mild coronary atherosclerosis (less than 20 percent narrowing). Vascular responses were evaluated by quantitative angiography. In several segments each of four normal coronary arteries, acetylcholine caused a dose-dependent dilation from a control diameter of 1.94 +/- 0.16 mm to 2.16 +/- 0.15 mm with the maximal acetylcholine dose (P less than 0.01). In contrast, all eight of the arteries with advanced stenoses showed dose-dependent constriction, from 1.05 +/- 0.05 to 0.32 +/- 0.16 mm at the highest concentration of acetylcholine (P less than 0.01), with temporary occlusion in five. Five of six vessels with minimal disease also constricted in response to acetylcholine. All vessels dilated in response to nitroglycerin, however. We conclude that paradoxical vasoconstriction induced by acetylcholine occurs early as well as late in the course of coronary atherosclerosis. Our preliminary findings suggest that the abnormal vascular response to acetylcholine may represent a defect in endothelial vasodilator function, and may be important in the pathogenesis of coronary vasospasm. PMID- 3093862 TI - Treatment of precocious puberty in the McCune-Albright syndrome with the aromatase inhibitor testolactone. AB - The McCune-Albright syndrome is characterized by cafe au lait spots, fibrous dysplasia of bones, and sexual precocity. Girls with precocious puberty due to this syndrome have episodic increases in serum estrogen levels together with the formation of large ovarian cysts. The serum gonadotropin levels are typically suppressed, and the precocious puberty has not responded to treatment with long acting analogues of luteinizing hormone-releasing hormone (LHRH). Encouraged by our initial success in a pilot study of one patient, we have now treated five girls with the McCune-Albright syndrome with the aromatase inhibitor testolactone, which blocks the synthesis of estrogens. Testolactone decreased the levels of circulating estradiol (P less than 0.05) and the ovarian volume (P less than 0.05), and there was a return to pretreatment levels after testolactone was stopped. During treatment, the peak responses of luteinizing hormone and follicle stimulating hormone to stimulation by LHRH rose above suppressed pretreatment levels--significantly above pretreatment levels for follicle-stimulating hormone (P less than 0.02)--and then returned to pretreatment levels after testolactone was discontinued. Growth rates fell in three patients during treatment but could not be assessed in the other two because of bone deformities. The mean rate of bone maturation decreased and menses stopped in three of the four girls who were menstruating regularly. We conclude that testolactone is an effective treatment of precocious puberty in the McCune-Albright syndrome. PMID- 3093863 TI - Anticystinuric effects of glutamine and of dietary sodium restriction. AB - We studied four patients with cystinuria to assess the effects of glutamine and dietary sodium on the urinary excretion of dibasic amino acids. In Patient 1, at an ad libitum dietary sodium intake of about 300 mmol per day, oral administration of glutamine led to reproducible and marked anticystinuria and antiornithinuria, whereas the excretion of lysine and arginine was not significantly affected. In Patient 2, at an ad libitum dietary sodium intake of about 150 mmol per day, no effect of glutamine could be demonstrated in studies lasting up to three weeks. Since the principal difference between Patients 1 and 2 was their dietary intake of sodium, Patient 3 was studied during dietary sodium intakes of 150 and 300 mmol per day. His cystine excretion was found to be higher at 300 than at 150 mmol per day. Glutamine suppressed his cystine excretion at a sodium intake of 300 mmol per day but had no effect at 150 mmol per day. When the effect of a further reduction in sodium intake alone was studied in a fourth patient, a decrease of 150 to 50 mmol per day was found to reduce cystine excretion markedly within 17 days. The low-sodium diet alone also reduced the excretion of lysine, arginine, and ornithine. We conclude that glutamine may reduce the excretion of dibasic amino acids at a high sodium intake but not at an intake of about 150 mmol per day. However, since a sodium-dependent excretion of the dibasic amino acids occurs at an intake down to about 50 mmol of sodium per day, dietary restriction of sodium can provide a safe approach to the treatment of cystinuria. PMID- 3093864 TI - The molecular basis of severe hemophilia B in a girl. PMID- 3093865 TI - Health care for the poor. A public-policy imperative. PMID- 3093866 TI - Opioid peptides: medicinal chemistry. PMID- 3093867 TI - Dermorphin: autonomic pharmacology and structure-activity relationships. PMID- 3093868 TI - Dehydro and cyclopropyl amino acids and peptides. PMID- 3093869 TI - Synthesis of opioid peptide analogs. PMID- 3093870 TI - Conformations of opioid peptides as determined by nuclear magnetic resonance and related spectroscopies. PMID- 3093871 TI - Conformational analysis of opioid peptides and the use of conformational restriction in the design of selective analogs. PMID- 3093872 TI - Stereochemically constrained enkephalin analogs containing alpha-aminoisobutyric acid and 1-amino-cyclopentane-1-carboxylic acid. PMID- 3093873 TI - Enkephalin conformation in solution: a perspective from vibrational spectroscopic studies. PMID- 3093874 TI - Conformational features of the opioid peptides in the solid state: a review of X ray crystallographic research. PMID- 3093875 TI - The search for nonaddicting strong analgesics: hopes and frustrations. PMID- 3093876 TI - Opioid peptides: molecular pharmacology, biosynthesis, and analysis. PMID- 3093877 TI - Computer analysis of radioligand data: advantages, problems, and pitfalls. AB - Mathematical modeling combined with nonlinear least-squares curve fitting provides a systematic, objective, reproducible, and consistent method to aid the interpretation of ligand-binding data. It forces the experimentalist to formulate hypotheses in an unambiguous manner and to consider alternative, closely related models as plausible counter-hypotheses. Modeling provides estimates of the "goodness-of-fit" of the theory to the data and estimates of the minimal uncertainty of the parameters. With the availability of many programs for micro- and mini-computers, as well as mainframe computers, these methods are now becoming widely used. Accordingly, we must emphasize a number of potential problems and limitations, based on our experience. Interpretation of results of modeling study should be made, in light of the following points: no amount of computer analysis will compensate for "bad" or insufficient data, or for poor experimental design; the interpretation of the computer analysis is subject to the caveat that all underlying assumptions must be satisfied; one must examine the data graphically in several coordinate systems (e.g., "raw data," as well as standardized residuals); one must continuously search for possible systematic biases or artifacts; one must closely examine the reproducibility of results between multiple experiments; and one must recognize that all of the "test tubes" in an experiment are not necessarily "independent observations" in a statistical sense. In view of these potential problems and limitations, one should always seek to corroborate results and interpretations of "modeling" studies of ligand binding by independent biochemical, biophysical, or structural evidence. In this context, ligand-binding studies, appropriately analyzed, can play a useful and constructive role. PMID- 3093878 TI - Biosynthesis of opioid peptides. PMID- 3093879 TI - Current status of RIA methods for the analysis of enkephalins and endorphins. PMID- 3093880 TI - Folding and enzymatic processing of precursors of biologically active peptides and proteins. PMID- 3093881 TI - Peptides as drugs in the treatment of opiate addiction. PMID- 3093882 TI - Opioid peptides as drug products: FDA regulatory requirements. PMID- 3093883 TI - A few thoughts on the development and regulation of neuropeptides. PMID- 3093884 TI - Proenkephalin biosynthesis in the rat. PMID- 3093885 TI - Isolation and identification of opioid peptides. PMID- 3093886 TI - Parasitology. Improving prospects for a schistosomiasis vaccine. PMID- 3093887 TI - Two antigen-independent adhesion pathways used by human cytotoxic T-cell clones. AB - Cell-cell adhesion is essential for many immunological functions, including interaction of cytotoxic T lymphocytes (CTLs) with their targets. We have explored CTL-target interactions using well-characterized cloned human CTLs. Conjugate formation between these CTLs and many antigen-negative targets is almost as efficient as with specific target cells, but does not lead to target cell lysis. Thus, on specific target cells, adhesion by antigen-independent pathways may occur concurrently with or precede antigen recognition. The molecules LFA-1, CD2 (T11, LFA-2) and LFA-3 have been shown to be involved in human CTL conjugation with and lysis of specific target cells. Here we describe monoclonal antibody inhibition studies using individual monoclonal antibodies and mixes which demonstrate (1) that LFA-1, CD2 and LFA-3 are involved in antigen independent conjugate formation; and (2) suggest that CD2 and LFA-3 are involved in one pathway and LFA-1 in another. We confirmed the existence of distinct pathways by the demonstration that LFA-1-dependent adhesion requires divalent cations and is temperature-sensitive whereas CD2- and LFA-3-dependent adhesion does not require divalent cations and is temperature-insensitive. Together with previous data, our studies suggest that CD2 on the effector interacts with LFA-3 as its ligand on targets. PMID- 3093888 TI - Weak acids may act as teratogens by accumulating in the basic milieu of the early mammalian embryo. AB - Among the eleven drugs or chemicals which are well-documented human teratogens, eight (or their main metabolites) are weak acids whereas none is a weak base. Moreover, 23 out of 32 acids tested have been found to be teratogenic in at least one animal species. The acidic property of drugs may therefore be an important determinant of teratogenicity. We demonstrate here that the intracellular pH (pHi) of the mouse and rat embryo is higher than that of maternal plasma, as determined by the relative accumulation of dimethadione. The antiepileptic drug valproic acid and its pharmacologically active unsaturated metabolite accumulate in embryonic tissue to higher concentrations than in maternal plasma, whereas the essentially neutral amide of valproic acid (valpromide) or ethosuximide do not accumulate in the embryo; we further demonstrate in the rat that the pHi of the embryo decreases with advancing gestation; in general agreement with the pH partition hypothesis, the exposure of the embryo to valproic acid also decreases significantly during that period. Furthermore, the amides of two weak acid teratogens, valpromide and methoxyacetamide, and the imide ethosuximide, are much less teratogenic than their acid counterparts. Our results suggest that weakly acidic drugs, by virtue of their physico-chemical nature, accumulate in the early embryo with its relatively high pHi. PMID- 3093889 TI - Maternal control of Drosophila segmentation gene expression. AB - Several genes have been identified that are involved in establishing the segmented body pattern during development of the fruit-fly Drosophila melanogaster. These fall into several classes on the basis of the kind of alteration to the wild-type segmentation pattern observed in mutant embryos. For example, mutations of the pair-rule class, such as fushi tarazu (ftz), cause the deletion of pattern elements with a two-segment periodicity; those of the gap class, such as knirps, cause the deletion of contiguous groups of segments. The availability of antibodies against the ftz protein has allowed its spatial pattern of expression to be studied during the development of wild-type and mutant embryos. The aim of the latter kind of experiment is to investigate possible interactions between these important genes. We have recently reported that knirps mutations cause a striking alteration to the pattern of transverse stripes of ftz expression usually seen during embryogenesis. Knirps is a zygotically-expressed gene, but recently a class of maternally-active genes has been identified that causes similar defects in pattern formation. We have now investigated the pattern of ftz expression in mutants of this class and have found that while they do have features seen in knirps mutants, they also exhibit significant differences between the different mutations reflecting the distinct but overlapping domains of gene activity. These observations demonstrate that maternally-active segmentation genes regulate zygotic gene expression, and that some of their effects on ftz may be directed through the knirps gene. PMID- 3093890 TI - Phenotypic changes induced by a mutated ras gene during the development of Dictyostelium transformants. AB - The ras proto-oncogene, found in all eukaryotes so far examined, encode s a protein with guanine nucleotide-binding and GTPase activity. Gene disruption experiments in yeast indicate that ras is essential for cell growth. Anit-sense mutagenesis approaches suggest that this is also true for Dictyostelium. Most mutations causing an amino-acid substitution for Gly 12 result in decreased GTPase activity and produce a transforming phenotype. In yeast, a Gly 19---- Val 19, missense mutation (Gly 19 is similar to Gly 12 in mammalian and Dictyostelium ras proteins) causes a series of dominant phenotypes, including elevated adenylate cyclase activity. In mammalian cells there is no evidence that ras activates adenylate cyclase activity. D. discoideum contains a single ras gene (Dd-ras) that encodes a protein very similar to the mammalian ras protein and identical to c-ras at the potentially transforming positions. Dd-ras is expressed in vegetative cells and later in development in prestalk cells whereas ras protein is found in vegetative and developing cells. In the migrating pseudoplasmodium, ras protein is found in prestalk but not prespore cells, suggesting it is involved in the function and/or differentiation of the anteriorly localized prestalk cells. In this report we examine the effects of expression of a Dd-ras gene carrying a Gly-12----Thr 12 missense mutation. PMID- 3093891 TI - T-cell responses to human AIDS virus in macaques immunized with recombinant vaccinia viruses. AB - There is much interest in developing vaccines against acquired immune deficiency syndrome (AIDS), which is caused by a retrovirus termed human immunodeficiency virus (HIV). Isolates of this virus include human T-lymphotropic virus type III (HTLV-III), lymphadenopathy-associated virus (LAV), and AIDS-associated retrovirus (ARV). Several approaches towards the development of an AIDS vaccine result in the production of antibodies in subprimates. These methods involve the use of: antigens isolated from the AIDS virus; viral antigens expressed by transfected cells or by recombinant vaccinia viruses; and particular synthetic peptides of viral antigens. Because T-cell-mediated immunity (in addition to antibodies) is involved in resistance to diseases and death caused by various enveloped viruses, we sought to determine whether potential AIDS vaccines can induce T-cell responses against the AIDS virus. Here we report that immunization of non-human primates, Macaca fascicularis (macaques), with recombinant vaccinia viruses that express LAV envelope glycoproteins gp41 and gp110 results not only in the production of antibodies against the LAV envelope antigens but also in the generation of T-cells that proliferate and produce the lymphokine interleukin-2 (IL-2), in response to stimulation with purified LAV. We believe this is the first report demonstrating T-cell-mediated immunity to the virus that causes AIDS. PMID- 3093892 TI - Isolation of complementary DNA clones encoding the human lymphocyte glycoprotein T1/Leu-1. AB - The T1/Leu-1/CD5 molecule, a human T-cell surface glycoprotein of relative molecular mass (Mr) 67,000, has been implicated in the proliferative response of activated T cells and in T-cell helper function. A similar involvement in T-cell proliferation has been reported for Ly-1, the murine homologue of T1. Here we report the complete amino-acid sequence of the T1 precursor molecule deduced from complementary DNA clones. The protein contains a classical signal peptide; a 347 amino-acid extracellular segment; a transmembrane region; and a 93-amino-acid intracellular segment. The extracellular segment contains many cysteine residues and is composed of two related structural domains separated by a proline/threonine-rich region. The T1 molecule has structural features characteristic of other receptor molecules. PMID- 3093893 TI - Distinctions in acetylcholine receptor activity. PMID- 3093894 TI - A novel family of human major histocompatibility complex-related genes not mapping to chromosome 6. AB - Thymocyte antigens CD1 [Thy,gp45,12] are thought to be the human counterparts of mouse thymus leukaemia (TL) antigens. Serological and biochemical analyses indicate that at least three subsets exist, the first of which (HTA 1/T6) was initially identified by the monoclonal antibody NA1/34. Like TL, CD1 are expressed on cortical thymocytes as well as on some lymphoid neoplasias, and resemble in structure major histocompatibility complex (MHC) class I antigens. However HTA 1/T6 is loosely associated with beta 2-microglobulin and is also found linked by a disulphide bridge to CD8(T8). A molecular genetic approach is needed to investigate the CD1 system, to clarify its relationship to TL antigens and to understand its regulation. We report the isolation of complementary DNA (cDNA) clones encoding a CD1 antigen. These clones reveal a novel family of genes which are MHC-related but are neither equivalent to mouse TL antigens nor linked to the MHC. PMID- 3093895 TI - Interaction of cell-type-specific nuclear proteins with immunoglobulin VH promoter region sequences. AB - All human and murine immunoglobulin heavy chain variable region (VH) genes contain the sequence ATGCAAAT approximately 70 nucleotides 5' from the site of transcription initiation. This octanucleotide, in reverse orientation, is also found in all light chain variable region (VL) genes, and in the immunoglobulin heavy chain transcriptional enhancer. Transfection studies have established that this octamer is involved in the lymphoid-specific transcription of immunoglobulin genes. Octamer-containing fragments have been reported to bind a factor present in nuclear extracts of human cell lines; however, identical binding activity was detected in both B lymphoid and non-lymphoid cells. Here we establish that nuclear extracts from distinct cell types differ in their ability to interact with octamer-containing fragments. We have also detected a DNA-protein interaction that may be involved in the cell-type specificity of immunoglobulin expression, and we have determined that a sequence upstream of the octamer participates in an interaction with a nuclear protein(s). PMID- 3093896 TI - Growth and differentiation of Bacillus subtilis under microgravity. PMID- 3093897 TI - Embryogenesis and aging of Drosophila melanogaster flown in the space shuttle. Preliminary analysis of experiment fly 15E. PMID- 3093898 TI - Flight hardware for chemical fixation of living material in the microgravity environment. PMID- 3093899 TI - Effects of prostaglandin I2 synthesized in the endothelium and in the smooth muscle on mechanical properties of the canine thoracic aorta. AB - In circular-cut strips prepared from canine thoracic aorta, acetylcholine (ACh) and A23187 relaxed endothelium-intact tissues [E(+) preparations] pre-contracted with noradrenaline or excess concentrations of K. These relaxations were associated with marked increases in the amount of 6-keto PGF1 alpha. After removal of the endothelium [E(-) preparations] the relaxation ceased, and the amounts of 6-keto PGF1 alpha were markedly reduced. In E(+) preparations, application of indomethacin attenuated the increase in 6-keto PGF1 alpha induced by ACh or A23187 in the presence of noradrenaline or high K, but not the endothelium-dependent relaxations. In E(-) preparations, ACh (0.1-10 microM) neither increased the amount of 6-keto PGF1 alpha nor produced a contraction. In dispersed single endothelial cells, A23187 markedly increased but 118 mM K did not modify the amount of 6-keto PGF1 alpha. Both noradrenaline and high K increased the production of 6-keto PGF1 alpha in the E(-) preparations but to a lesser extent than that in the E(+) preparations. This action was attenuated by indomethacin. The amplitude of the noradrenaline- and K-induced contractions was enhanced with indomethacin pretreatment in both E(+) and E(-) tissues. PGI2-Na (10 nM), reduced the amplitude of noradrenaline-induced contractions, concentration dependently and to the same extent in both E(+) and E(-) preparations. These results indicate that synthesis of PGI2 in the endothelium is not causally related to the endothelium dependent relaxation. PGI2 synthesized in the endothelium may not act directly on the muscle tissue, but PGI2 synthesized in the smooth muscle tissue may produce an inhibition of contraction. PMID- 3093901 TI - A language barrier. PMID- 3093900 TI - Potentiation by deprenyl of the autoreceptor-mediated inhibition of [3H]-5 hydroxytryptamine release by 5-methoxytryptamine. AB - The 5-hydroxytryptamine (5HT) receptor agonist, 5-methoxytryptamine, inhibited in a concentration-dependent manner the electrically-evoked release of 3H-5HT from superfused rat hypothalamic slices, with an IC50 of 560 nmol/l, without affecting the spontaneous outflow of radioactivity. In the presence of the selective monoamine oxidase B (MAO B) inhibitor, (-)-deprenyl (1 mumol/l), the concentration-effect curve for 5-methoxytryptamine was shifted significantly to the left, and the IC50 was decreased to 25 nmol/l. Under the same experimental conditions, the potency of the 5HT receptor agonist lysergic acid diethylamide (LSD) at inhibiting the electrically-evoked release of 3H-5HT was the same in the presence as well as in the absence of (-)-deprenyl. The IC50 values for LSD were 34 nmol/l in the absence of deprenyl, and 31 nmol/l in the presence of the MAO B inhibitor. It is concluded that deprenyl potentiates the inhibition by 5 methoxytryptamine of 3H-5HT release, by preventing its inactivation through MAO B. Since 5-methoxytryptamine may be present in the pineal gland of some species, the potent effects of this 5-HT receptor agonist on serotoninergic neurotransmission may be of physiological relevance. PMID- 3093902 TI - [Increased infection susceptibility in children with immunologic defense deficiency]. PMID- 3093903 TI - [Primary immunodeficiencies: development and trends]. PMID- 3093904 TI - [Secondary immunodeficiencies]. PMID- 3093905 TI - [Pseudothrombocytopenia caused by thrombocyte agglutination (EDTA pseudothrombocytopenia)]. PMID- 3093906 TI - [Intramural pseudodiverticulosis of the esophagus]. PMID- 3093907 TI - [Objective studies on the differences in personality of monopolar and bipolar depressed patients treated with lithium]. PMID- 3093908 TI - Copper stimulation of LHRH release from median eminence explants. I. A divalent metal specific process that does not require extracellular calcium. AB - We have previously shown that chelated copper stimulates the release of LHRH from explants of the median eminence area (MEA) incubated under in vitro conditions, and that this stimulation involves a ligand specific interaction. To further elucidate the mechanism of action of copper, we addressed two questions: (a) What is the divalent metal [metal(II)] specificity for this release process? (b) Is the stimulation of LHRH release by CuHis dependent on influx of extracellular calcium? MEA obtained from adult male rats were incubated for 15 min with one of the following divalent metals Cu, Ni, Fe, Zn, Cd or Mn (each complexed to histidine at an equimolar ratio; 100 microM) and then in the absence of metal for an additional period of 30 min. We found that CuHis and to a lesser extent NiHis stimulated LHRH release, and that FeHis, ZnHis, CdHis or MnHis did not do so. In addition, MEA were incubated for 15 min with CuHis in the presence or absence of CaCl2. Under these two conditions, the temporal pattern and magnitude of CuHis stimulated LHRH release were identical, indicating that extracellular calcium is not required for copper action. Since, in this series of metals, Cu2+ and Ni2+ are the most potent oxidizing agents, our finding strongly supports our previous proposition that an oxidation reaction is involved in the process of copper stimulation of LHRH release. It has yet to be elucidated whether copper action is totally independent of an increase in intracellular calcium or whether copper leads to LHRH release via mobilization of calcium from intracellular stores. PMID- 3093910 TI - Prolactin and TSH response to TRH and metoclopramide before and after l-thyroxine therapy in subclinical hypothyroidism. AB - The effects of the dopamine (DA) receptor antagonist metoclopramide on the plasma thyroid stimulating hormone (TSH) and prolactin (PRL) levels were studied in 8 patients with subclinical hypothyroidism (defined as absence of clinical signs of hypothyroidism with normal thyroid hormone levels, normal or slightly increased basal plasma TSH levels and increased and long-lasting TSH response to TRH) before and after l-thyroxine replacement therapy. Metoclopramide induced a significant (p less than 0.01) TSH release in the subclinical hypothyroid patients. Two weeks after l-thyroxine replacement therapy (50 micrograms/day), the TSH response to metoclopramide was completely blunted in subclinical hypothyroidism. In these patients a significant (p less than 0.01) inhibition of TSH response to intravenous thyrotropin-releasing hormone (TRH) was also observed after treatment with thyroid hormone. In analogy to the TSH behavior, plasma PRL secretion in response to metoclopramide and TRH administration was significantly (p less than 0.05) inhibited in the subclinical hypothyroid patients after l thyroxine replacement therapy. PMID- 3093909 TI - Cholinergic involvement in the growth hormone releasing hormone-induced growth hormone release: studies in normal and acromegalic subjects. AB - To throw light onto the mechanism(s) by which the cholinergic system influences growth hormone (GH) release, the effects of two muscarinic receptor blockers, pirenzepine and atropine, and of an acetylcholinesterase inhibitor, pyridostigmine bromide, on the GH response to GHRH-44 were studied in 19 normal volunteers. Moreover, the effects of pirenzepine administration on plasma GH levels both in basal conditions and after stimulation by GHRH-44 and TRH were studied in 9 acromegalics. Both pirenzepine (0.6 mg/kg i.v., 5 min before GHRH) and atropine (1 mg i.m., 15 min before GHRH) blunted the GH response to GHRH (1 microgram/kg i.v. bolus) (area under the response curve, AUC: 81.3 +/- 17.3 vs. 481.2 +/- 211.3 ng/ml/h for pirenzepine and 100.2 +/- 27.0 vs. 364.7 +/- 81.0 ng/ml/h for atropine; p less than 0.01). Pyridostigmine (120 mg orally, 30 min before GHRH) induced a variable but significant (p less than 0.02) rise in basal plasma GH levels and, furthermore, an unequivocal potentiation of the GH response to GHRH (AUC: 1044.6 +/- 245.3 vs. 481.2 +/- 211.3 ng/ml/h; p less than 0.01). In all but one acromegalics 0.6 mg/kg i.v. pirenzepine was unable to modify the basal GH levels whilst it showed a variable inhibitory effect on the GH response to GHRH. The GH response to TRH (200 micrograms i.v. bolus) was instead unmodified by pirenzepine. In conclusion, muscarinic receptor blockade inhibits while cholinergic potentiation seems to positively modulate the GH response to GHRH. Therefore, the cholinergic system seems to positively modulate the GHRH effect on somatotrophs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093911 TI - Effect of thyrotropin releasing hormone and some of its histidine analogs on the cardiovascular system and prolactin release in the conscious rat. AB - The cardiovascular and endocrine activity of three analogs of thyrotropin releasing hormone (TRH), 4-nitro-imidazole TRH (4-nitro-TRH), 2-trifluoro-methyl imidazole TRH (2-TFM-TRH) and 4-trifluoro-methyl-imidazole TRH (4-TFM-TRH), was compared to TRH in conscious rats. Injection of TRH or the three analogs (1 mg/kg or 5 mg/kg) into the arterial line induced increases in mean arterial pressure, pulse pressure and heart rate and raised plasma prolactin (PRL). None of the analogs were more potent than TRH in inducing cardiovascular changes. The 4-TFM TRH was significantly less potent than the 2-TFM-TRH in increasing blood pressure, while the nitro-TRH was more potent than the 2-TFM-TRH in producing tachycardia. TRH induced a two-fold increase in PRL at the 5 mg/kg dose, while both the fluorinated analogs elicited a 4 to 5 fold increase in PRL at the higher dose. The present results suggest that the receptors for TRH-elicited PRL release differ from TRH-receptors involved in its cardiovascular actions. PMID- 3093912 TI - Thyrotropin-releasing hormone metabolism is attenuated in the cerebrospinal fluid of the human neonate. AB - The present study was designed to investigate the ontogeny of thyrotropin releasing hormone (TRH) metabolism in human cerebrospinal fluid (CFS). The activity of pyroglutamate aminopeptidase (EC 3.4.11.8), the major enzyme catalyzing TRH metabolism in human CSF, was measured in CSF of 11 premature infants (gestational age, 29-39 weeks; birth weight, 1774 +/- 274 g), 8 newborn infants (term delivery; birth weight, 3648 +/- 240 g), and 11 adults (mean age, 29.6 +/- 1.5 years). Pyroglutamate aminopeptidase activity in CSF of premature and newborn infants was significantly lower (p less than 0.05) than that of adult CSF. These observed differences in the enzymatic activities were not due to changes in the affinity of the enzyme for its substrate TRH or the presence of enzyme inhibitor(s)/stimulator(s). PMID- 3093913 TI - Further studies on the effects of a thyrotropin releasing hormone analogue on locomotor activity in the rat. AB - In these experiments, the relationship between two of the variables of locomotion, stepping frequency and velocity, after injection of the TRH analogue RX77368 (10 mg/Kg i.p.), has been studied. A shift towards higher stepping frequencies was observed, confirming previous observations. However, there was no difference between the velocities of locomotion produced by treated and control rats. In the treated rats the relationship between stepping frequency and velocity was disturbed, such that a higher stepping frequency was employed to attain any particular velocity. This was accompanied by a reduction in stride length. Possible reasons for this disturbance are discussed in terms of changes in muscle stiffness and proprioceptive reflexes. PMID- 3093914 TI - Comparison of nitroprusside, nitroglycerin, and deep isoflurane anesthesia for induced hypotension. AB - Three methods of inducing hypotension were studied for their effects on the cardiovascular system and intrapulmonary shunting. Thirty patients were anesthetized with isoflurane in 70% N2O to a total of 1.25 to 1.3 MAC. Patients were divided into three groups of 10 each on the basis of the drug used to induce hypotension; sodium nitroprusside (SNP), nitroglycerin (NTG), or deep isoflurane anesthesia (ISF). Cardiac index was significantly decreased by NTG and ISF at a mean arterial blood pressure of 40 mm Hg compared to SNP (P less than 0.05). Systemic vascular resistance was decreased in all groups. Mixed venous oxygen content was significantly decreased from control in the NTG and ISF groups. There was no difference between the groups in arterial and mixed venous O2 content. Intrapulmonary shunting decreased with induction and, in the NTG and SNP groups, increased slightly but not significantly with induction of hypotension. Our data do not show a clear superiority of any agent over the other to induce hypotension, although SNP and perhaps ISF appear to be better than NTG to induce hypotension. PMID- 3093915 TI - Nutritional support and neurotrauma: a critical review of early nutrition in forty-five acute head injury patients. AB - Forty-five acute head trauma patients were randomized into a neurotrauma nutritional study to compare the efficacy of two forms of standard nutritional supplementation; namely total parenteral nutrition (TPN) versus enteral nutrition (NG). Forty patients were male, 5 were female, with a median age of 28 years. The mean admitting Glasgow coma scale score was 5.8. Patients were given high calorie and nitrogen feedings for the 14 days of the study period in an attempt to achieve positive calorie and nitrogen balance. TPN patients had significantly higher mean daily nitrogen intakes (P less than 0.01) and mean daily nitrogen losses (P less than 0.001) than the NG fed patients; however, no significant differences were discovered with respect to maintenance of serum albumin levels, weight loss, the incidence of infection, nitrogen balance, and final outcome. The exaggerated nitrogen excretion experienced by patients fed large nitrogen loads illustrates a problem in achieving nitrogen equilibrium in acute head injured patients. PMID- 3093916 TI - Urinary 3-methoxy-4-hydroxyphenylglycol in affective and schizophrenic patients. Behavior and symptom correlates. AB - The relations between urinary 3-methoxy-4-hydroxyphenylglycol, (MHPG) excretion, ward behavior in two environments (dayroom and gym), and symptomatology were examined in 58 psychiatric inpatients. In the total patient sample, idiosyncratic behaviors and body activity correlated positively with MHPG levels. Among depressed patients MHPG correlated negatively with eating lunch in the dayroom and positively with self-reported appetite loss, suggesting that appetite disturbance in major depression may be due to high norepinephrine turnover. The results support the utility of naturalistic observation instruments in exploring the relations between psychopathology and biological substrates. PMID- 3093917 TI - An immunohistochemical study of endopeptidase-24.11 ("enkephalinase") in the pig nervous system. AB - Endopeptidase-24.11, a plasma membrane ectoenzyme with the ability to hydrolyse a variety of neuropeptides, has been localized in the pig nervous system by an immunoperoxidase technique. The endopeptidase was mapped in cryostat sections of the fore and mid-brain to the following structures: caudate-putamen, globus pallidus, olfactory tubercle, nucleus interpeduncularis and substantia nigra. Endopeptidase-24.11-like immunoreactivity was also found in the pia mater, choroid plexus and ependymal lining of the central canal. In the spinal cord, weak staining was observed in the dorsal horn, but strong staining was found in the dorsal root ganglia and nerve roots. Within the central nervous system, endopeptidase immunoreactivity was confined to gray matter and within the positive areas of the striatum densely staining areas, corresponding to striosomes, were discernible. These well-defined structures were exploited in serial sections to examine the alignment of the enzyme-rich patches of neuropil with correspondingly strong staining for other antigens. A consistent match was observed with a monoclonal antibody to neurofilament protein, but there was a poor correlation with a polyclonal antibody to glial fibrillary acidic protein. Substance P-like and [Leu]enkephalin-like immunoreactivity were also studied in sections adjacent to those stained for the endopeptidase. Good matching between enzyme-rich and peptide-rich areas was observed, but some enkephalin-rich areas did not align with enzyme staining and indeed endopeptidase-rich areas were not necessarily matched with areas rich in either peptide. These findings suggest a neuronal rather than an astrocytic location for endopeptidase-24.11 in the CNS and lend support to the view that it plays a central role in neuropeptide metabolism at membrane surfaces. In the peripheral nervous system, the endopeptidase was located in Schwann cell membranes surrounding dorsal root ganglion cells and nerve fibres, while in the pituitary the main concentration was in the adenohypophysis, where only a proportion of the endocrine cells were found to be immunoreactive. PMID- 3093918 TI - Transfer factor therapy in multiple sclerosis: a three-year prospective double blind clinical trial. AB - One hundred five patients with MS were divided into three groups matched for age, sex, and disability, and treated with either placebo, transfer factor prepared from leukocytes of random donors, or transfer factor from leukocytes of family members living with the patients. There were no differences in the three treatment groups for changes in disability, activities of daily living, or evoked potentials. Eighteen months of transfer factor therapy had no effect on gamma interferon production or natural killer cell activities. PMID- 3093920 TI - AIDS. Case for diagnosis, 1986. Military Medicine. PMID- 3093919 TI - Perspective on carbamazepine-induced water intoxication: reversal by demeclocycline. AB - Carbamazepine (CBZ)-induced water intoxication occasionally limits its usefulness in refractory seizures and trigeminal neuralgia. Fluid restriction, CBZ dose reduction, or concomitant phenytoin therapy may be impractical or ineffective. Demeclocycline (7-chloro-6 demethyl tetracycline) (DMC) corrected the CBZ-induced water intoxication in a 51-year-old man with refractory complex partial seizures and a normal antidiuretic hormone (ADH) level. DMC inhibits ADH-sensitive adenylate cyclase activity in the renal collecting duct and may be useful in correcting the ADH-like or renal antidiuretic effect of CBZ. PMID- 3093921 TI - The application of digitized image transmission to forensic dentistry. PMID- 3093922 TI - Post-traumatic epilepsy in the military. PMID- 3093924 TI - Military occupational specialty medical retention board: promises and problems. PMID- 3093923 TI - IgE in allergic disease in a veteran population. PMID- 3093925 TI - The physiologic and psychological effects of a 5-week and a 16-week physical fitness program. PMID- 3093926 TI - Implications to forensic psychiatry of post-traumatic stress disorder: a review. PMID- 3093927 TI - Effect of nifedipine on gastric emptying. PMID- 3093928 TI - Inverted duplication of chromosome 15: inv dup (15). PMID- 3093929 TI - An analysis of febrile illnesses among members of the Malaysian Police Field Force. PMID- 3093930 TI - Wound infection in elective colon surgery. PMID- 3093931 TI - Delayed recognition of carotid artery injury due to blunt trauma. PMID- 3093932 TI - Injections followed by a sterile abscess. PMID- 3093933 TI - Smoke in the workplace: cost and health consequences. PMID- 3093934 TI - [Effect of TRH and anti-TRH serum in experimental ulcerogenesis in the rat]. PMID- 3093935 TI - Turnover of central biogenic amines in two-kidney, one-clip renal hypertensive rats. AB - Turnover rates, as estimated from the accumulation of the intermediates dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) following decarboxylase inhibition, were used to investigate the relationship between central catecholaminergic and serotonergic neurons and the development of hypertension in 2-kidney, 1-clip renal hypertensive rats. Results indicated that at one week following clipping, DOPA accumulation was increased in the midbrain pons. At 5 weeks no changes were observed. At 20 weeks a lower accumulation of both DOPA and 5-HTP was observed in the posterior hypothalamus while in the medulla oblongata DOPA accumulation was lower and in the midbrain-pons 5-HTP accumulation was reduced. PMID- 3093936 TI - Effects of human pancreatic growth hormone-releasing hormone and fragments of rat hypothalamic growth hormone-releasing hormone on the activity of rat brain neurons. AB - The effect of human pancreatic growth hormone-releasing factor (hpGRF), rat hypothalamic GRF1-29 (rhGRF1-29) and rhGRF3-40 on spontaneous extracellular activity was studied in urethane anesthetized, male rats. The results show that these peptides similarly depress the firing rate of responsive neurons in the amygdala, caudate-putamen and globus pallidus. A single neuron was excited by hpGRF and it was localized to the medial amygdala. These findings are in line with the hypothesis that GRF has effects on the central nervous system in addition to regulating pituitary growth hormone secretion. PMID- 3093938 TI - Enteral nutrition. PMID- 3093937 TI - Helping the patient and family adjust to L.T.C. living. PMID- 3093940 TI - Nutritional support: an overview of general principles. PMID- 3093939 TI - Total parenteral nutrition. PMID- 3093941 TI - Physicians, hospitals, and diagnosis related groups (DRGs): is control the issue? PMID- 3093942 TI - Recent advances in the nutritional and metabolic management of critically ill surgical patients. PMID- 3093944 TI - DRGs: what nurses need to know. PMID- 3093943 TI - DRG 001: a multihospital comparison. PMID- 3093946 TI - Selling OH. An uphill struggle. PMID- 3093945 TI - Unreliable amniotic fluid bilirubin measurements in isoimmunized pregnancies in sickle cell disease patients. PMID- 3093947 TI - Selling OH. In-house nursing--what's the value. PMID- 3093948 TI - [Acceptable risks in adjuvant therapy]. AB - The definition of acceptable risks in adjuvant therapies has to be based on the evaluation of the cost-benefit relationship. The possible benefit can only be determined by prospective clinical trials for each tumor category. Individually, the possible benefit cannot be weighed as long as no method for the detection of micrometastases is available. Statistically, successful or promising adjuvant treatments, treatments in the experimental phase, treatments with controversial or with clearly negative results can be defined for the various malignant tumors. The risks consist in short-, medium- and long-term side-effects of adjuvant therapies, especially of adjuvant chemotherapy. Of special importance for the cost-benefit evaluation are long-term organ toxicities and the induction of second neoplastic diseases. The definition of acceptable risks involves not only medical, but also ethical considerations. But all these considerations should be based as far as possible on objective facts and not on prejudice. PMID- 3093949 TI - Hemophilia A, idiopathic thrombocytopenia and HTLV-III-infection impressive remission after splenectomy: a case report. PMID- 3093950 TI - Treatment of recurrent squamous papillomata of the conjunctiva by carbon dioxide laser vaporization. AB - Complete resection of recurrent conjunctival squamous papillomata frequently may be exceedingly difficult, since such lesions are typically friable and multilobulated. Recurrent lesions often fill the fornicies and spill onto the lid margins. Moreover, since the human papillomavirus (HPV) has been linked to some of these lesions, there remains the further possibility of spread with "cold knife" resection. We discuss the benefits of carbon dioxide laser vaporization therapy for recurrent squamous papillomata of the conjunctiva that have not responded to resection and cryotherapy or topical immunotherapy. The carbon dioxide laser facilitates resection by providing a bloodless field, and reduces the possibility of viral seeding of the conjunctiva by sterilizing the operative site and sealing the lymphatics. PMID- 3093951 TI - AIDS: an ethical challenge for our time. PMID- 3093952 TI - Psychosocial and ethical issues of AIDS health care programs. AB - The psychiatric, psychosocial, and ethical considerations in the design and evaluation of health care programs for AIDS patients and others with HIV infection are described in this article. The responsibilities of health care providers are considered in the context of the history and epidemiology of AIDS, previous responses of the health care delivery system, and the concerns of the general public. General guidelines for program development are set forth; these guidelines embody ethical principles, the role of education in altering the behavior and attitudes of patients and health care workers, the optimal levels of and precautions for infection control, and the evaluation of a patient's competency and judgement. Several examples of the use of these guidelines to resolve difficult policy issues arising in the treatment of patients with AIDS or HIV infection are also provided. PMID- 3093953 TI - AIDS: one psychosocial response. AB - In 1982 only 20 cases of AIDS were recognized in the Chicago area. Today 383 cases are known. The Howard Brown Memorial Clinic provides the 120 surviving individuals and their loved ones with comprehensive and coordinated services ranging from financial assistance to significant other support groups. PMID- 3093954 TI - Health care advocacy for AIDS patients. AB - The ombudsman position was created at the Gay Men's Health Crisis (GMHC) in New York to link AIDS patients with the health care system. The department, which has served 3,400 clients since 1982, handles complaints and problems relating to such areas as ambulatory care, home attendant care, and advocacy for improved patient care. Social work, discharge planning, and mental health issues are discussed. The efforts of the ombudsman office has led to many supportive relationships with providers and increased awareness of the needs by political organizations. PMID- 3093955 TI - Microinjection of dopamine agonists into nucleus raphe magnus affects nociception in rats. AB - Microinjection of the dopamine receptor agonist apomorphine, and to a lesser extent dopamine itself, into the nucleus raphe magnus increased tail flick latency in conscious rats. The hypoalgesia was dependent on the integrity of catecholamine-containing pathways originating near the third ventricle and was diminished by systemic depletion of hydroxytryptamine. No simple neuronal circuitry could explain all the effects observed. PMID- 3093957 TI - [HLA and narcolepsy]. AB - A very strong association has been shown to exist between HLA-DR2/Dw2 and narcolepsy, both in Caucasoid and Mongoloid people. The gene responsible for susceptibility, HLA or linked with HLA, is probably transmitted as an autosomal dominant trait with incomplete penetrance. The investigation of DR2 is useful for the diagnosis of minor or incomplete forms in narcolepsy and in the detection of exposed subjects in families. This association opens up horizons concerning the mechanism of narcolepsy. Several hypotheses are discussed, in particular that of a multifactorial disease, in which an environmental agent and DR2 antigen, functioning as the product of an Ir gene, would play a role. PMID- 3093956 TI - [Celiac disease]. AB - Coeliac disease (CD) is a malabsorption syndrome mediated by gluten toxicity. In almost all populations studied CD is strongly associated with HLA.DR3 and to a lesser extent with DR7, the frequency of DR2 is often low. There is a highly significant excess of DR3/DR7 heterozygotes. Although the association of CD with HLA has been known for 15 years the mode of transmission is poorly understood. In multiple case families the segregation of haplotypes is in favour of a recessive mode of inheritance with low penetrance. The rare cases of CD negative for DR3 and DR7 are positive for DR4 and negative for DQw2, ruling out the intervention of DQw2 by linkage disequilibrium. A recent study tends to show an hyporesponsiveness of T lymphocytes from patients to an antigenic extract of gluten. PMID- 3093958 TI - [A model and 3 examples for understanding HLA and diseases: cis and trans complementation of MHC class II in juvenile insulin-dependent diabetes, juvenile rheumatoid arthritis and celiac disease]. AB - The heterozygous effect observed for the HLA and disease association in insulin dependent diabetes, juvenile rheumatoid arthritis and coeliac disease is interpreted in the view of recent cellular and molecular data of MHC class II molecules demonstrating the existence of hybrid HLA DQ molecules and conformational determinants created by Trans (or Cis) complementation. It is postulated that unique determinants created de novo by such mechanisms represent the structural basis for the altered immune response leading to the pathogenesis of these auto-immune diseases. PMID- 3093959 TI - Blood rheology and myalgic encephalomyelitis: a pilot study. AB - The blood rheology of EDTA-anticoagulated blood samples from blood donors and subjects considered to have myalgic encephalomyelitis was assessed by multiple shear rate viscometry and by multiple-pressure filterability. Although average viscosities of the two groups were different, the differences did not reach statistical significance. In contrast, the data from multiple-pressure filtration of whole blood showed significant differences between females at the lowest (2.5 cm of water) filtration pressure. It appears that the acute phase of the disorder is associated with changes in blood rheology which could impair microcirculatory blood flow. In contrast, the chronic state does not appear to be associated with rheological abnormalities. PMID- 3093960 TI - The histological and ultrastructural features of the epiphyseal plate in Morquio type A syndrome (mucopolysaccharidosis type IVA). AB - Tissue from the epiphyseal plate of a patient with Morquio type A syndrome (mucopolysaccharidosis type IVA) was studied by undecalcified histological and electron microscopical techniques. Cartilage cells in the plate were vacuolated to a variable degree. The orderly proliferating structure of the epiphyseal plate was absent and calcification was markedly reduced. The related bone tissue was morphologically normal although reduced in quantity. PMID- 3093961 TI - In vitro antibacterial activity of enoxacin (CI-919). AB - Antibacterial activity of enoxacin was evaluated against more than 3,700 clinical isolates using the agar-dilution method and an inoculum of 10(4)-10(5) cells per site. For comparison other antibiotics appropriate for each species were also included. For most enterobacteria and for Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, the MIC90 of enoxacin was below 2 mg/l. Serratia marcescens was more resistant; the MIC90 being 4 mg/ml. Enoxacin also showed high activity against Campylobacter jejuni and Neisseria gonorrhoeae. Streptococci were comparatively resistant, 32 mg/l to 64 mg/l of the compound being required to inhibit 90% of strains. PMID- 3093962 TI - Normocarbic hyperventilation fails to induce pulmonary vasodilation. AB - The pulmonary vasodilator effect of increased rate of mechanical ventilation, with and without respiratory alkalosis, was studied in chronically instrumented newborn lambs. Pulmonary hypertension was first induced by ventilating with a hypoxic gas mixture. Subsequent respiratory alkalosis caused significant decreases in pulmonary arterial pressure and pulmonary vascular resistance. When normocarbia was re-established by adding carbon dioxide to the inspired gas, with the ventilator rate being held constant, the pressure and resistance returned to the baseline hypertensive state. Therefore, mechanical factors, either direct or indirect, appear to be of minor importance in the mechanism of pulmonary vasodilation secondary to frequency-induced hyperventilation. PMID- 3093963 TI - Diaphragmatic pressures in piglets: transvenous versus direct phrenic nerve stimulation. AB - We examined transdiaphragmatic pressure (Pdi) generation during both direct (DPNS) and transvenous (TVPNS) modes of phrenic nerve stimulation in anesthetized piglets of varying postnatal age. Pdi measurements during TVPNS were not statistically different from those obtained during DPNS (p greater than 0.10). Furthermore, a good correlation (r = 0.98, p less than 0.001) was obtained when the mean Pdi measurements obtained by both methods were compared. We conclude that TVPNS can be used in lieu of DPNS to generate Pdi. Furthermore, our data suggest that this technique can be used to study the effects of various experimental manipulations on diaphragmatic force output within a developmental context. PMID- 3093965 TI - Central venous silicone elastomer catheter placement by basilic vein cutdown in neonates. AB - There is a need for central venous access in small premature infants and other neonates when enteral feeding is not tolerated or is contraindicated. We placed 83 small (0.635-mm od) silicone elastomer catheters by basilic vein cutdown through a subcutaneous tunnel in 79 patients during a 12-month period. Thirty five patients (44%) weighed less than 1,000 g. Each patient on whom the procedure was attempted had successful placement of a catheter, and they remained in place a mean of 20 days (range three to 82). Patients had a mean weight gain of 15 g per day of catheter use. Sixty-two catheters (75%) were removed electively, 13 (16%) secondary to complications, six (7%) because of patient deaths (none catheter related), and two (2%) were accidentally dislodged. Two episodes of catheter-related sepsis (0.12 episodes per 100 days of catheter use) caused by Candida albicans and Staphylococcus epidermidis were encountered. Other complications included one subclavian vein thrombosis, eight catheter occlusions, and two local arm inflammations. This technique proved to be a safe, easy, and inexpensive method to administer parenteral nutrition to neonates, especially those weighing less than 1,000 g. PMID- 3093964 TI - Aminophylline reduces hypoxic ventilatory depression without increasing catecholamines. AB - Aminophylline reduces hypoxic ventilatory depression in newborn piglets and can enhance the release of catecholamines (CATs), which in turn may stimulate ventilation. To determine if the effect of aminophylline on ventilation was due to the release of CATs, we measured plasma CATs and ventilation in two groups of spontaneously breathing newborn piglets less than 4 days old, treated with either aminophylline (n = 7) or normal saline solution (n = 6) during both normoxia and hypoxia. The piglets were anesthetized with ketamine and xylazine and intubated, and the femoral artery was catheterized. Epinephrine and norepinephrine were measured before and 30 minutes after treatment with aminophylline (15 mg/kg) or normal saline. The animals were exposed to 10% oxygen and the CATs again measured after 5 minutes of hypoxia. Respiratory rate, expiratory flow integrated to minute ventilation (VE), heart rate, and blood pressure were continuously recorded. CATs were assayed by high-pressure liquid chromatography with electrochemical detection. Treatment with aminophylline during normoxia was associated with an increase in tidal volume. During hypoxia, treatment with aminophylline prevented a fall in VE and respiratory rate seen in the normal saline group. Epinephrine and norepinephrine increased during hypoxia, but there was no difference between the groups at 5 minutes. In our model the increase in CATs observed during hypoxia was not enhanced by aminophylline. This is consistent with the hypothesis that some mechanism other than catecholamine release is responsible for the effect of aminophylline in reducing neonatal hypoxic respiratory depression. PMID- 3093966 TI - Varicella: complications and costs. AB - Varicella (chickenpox) has long been considered a benign, inevitable disease of childhood. Complications are generally mild and rarely severe, and virtually every individual is infected by adulthood. Infection is associated, however, with a high risk of serious complications in certain high-risk groups, such as leukemic children. Concerns about the severity of varicella in this population have led to the development and testing of a live, attenuated vaccine. Because of the favorable results thus far available, the vaccine may soon be licensed for use in high-risk individuals. The fact that a vaccine may soon be available has led to an increased interest in the potential benefits of a childhood varicella vaccine program. The costs associated with varicella infection in normal persons without a varicella vaccination program have been estimated to be approximately $400 million, 95% of which is the cost of caring for a child at home. Vaccination of normal 15-month-old children with a safe and effective vaccine with long lasting immunity could reduce the cost by 66% and result in a savings of $7 for every dollar spent on the vaccination program. This assumes that vaccine would be administered only once with measles, mumps, and rubella vaccine, that there would be no increase in the number of varicella cases in older persons who are at increased risk for complications, and that there would be no deleterious effect on the occurrence and severity of herpes zoster.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093967 TI - Prospective pricing system for tertiary neonatal intensive care. AB - This study assessed the potential impact of the federal neonatal diagnosis related group (DRG) pricing system upon reimbursement to a state neonatal intensive care program. Data for length of intensive care unit stay, procedures, hospital charges, and audited cost reports from the state of Florida's ten regional neonatal intensive care centers were analyzed for 8,492 neonates whose charges totaled $118 million. Mean lengths of stay in these tertiary care centers were substantially longer than those reported for the federal DRGs, which were based on community hospital data. If federal DRG-based reimbursement to hospitals were implemented in Florida's perinatal intensive care program, compensation would range from 9% to 56% of actual hospital care charges. Federal DRG price rates were not predictive of hospital charges. Only 16% of the total variation in hospital charges was explained by differences among federal DRG rates (R2 = .16). Analysis of data by major determinants of resource consumption provided groups more homogeneous with respect to hospital charges and, hence, cost. Therefore, we developed a prospective pricing system that used modifications of federal newborn DRG system. These modifications resulted in a threefold increase in R2 (.52). Our proposed system permits prediction of cost and reimbursement for infants by three criteria: birth weight, need for mechanical ventilation and/or major surgery, and survival status and length of survival for those who die. PMID- 3093968 TI - Alternative to diagnosis-related groups for newborn intensive care. AB - Clinical and billing data were collected on all admissions to six California newborn intensive care units during a 6-month period. Charges were adjusted to costs using Medicaid cost to charge ratios and for inflation, and patients were classified by the diagnosis-related group (DRG) system. Costs were from 97% to 708% more than the proposed DRG reimbursement levels. Regression analysis showed that DRGs explained 22% of the variation in costs. An alternative model using binary variables to control for birth weight, assisted ventilation, surgery, survival, multiple births, and mode of discharge explained 42% of the variation in costs. In contrast to other proposed DRG alternatives, this simple model does not require special training or subjective decision-making. PMID- 3093969 TI - Does breast-feeding protect against infections in infants less than 3 months of age? AB - To determine whether breast-feeding protects infants from infections, a case control study was conducted. The cases were previously healthy children who were admitted to Yale-New Haven Hospital for an infectious illness at or before 90 days of age. The controls were chosen from the log of births and matched to the cases for five important demographic variables. In addition, logistic regression models were used to adjust the results for other potential confounders. To minimize the potential surveillance bias that might occur if formula-fed and breast-fed infants with the same degree of illness have a different probability of being hospitalized, the case-control pairs were stratified by the severity of the medical condition of the case at the time of hospitalization. For the 281 case-control pairs, the matched odds ratio was .50 (95% confidence interval .32, .77; P less than .005), which indicates that breast-feeding is protective against infections. However, this apparent protective effect was diminished substantially when the data were stratified according to the severity of illness: the matched odds ratio for the 164 infants with serious illnesses was .79 (.47, 1.32; P less than .50), and for the 117 infants with mild illnesses it was .17 (.03, .44; P less than .001). These stratified results suggest that breast-feeding protects infants from hospitalization rather than from infections. Failure to consider the problem of surveillance bias may lead to erroneous conclusions about the protective effect of breast-feeding. PMID- 3093970 TI - [Health status of children born to mothers treated with hormonal preparations for infertility]. PMID- 3093971 TI - [Significance of tuberculous infection in pediatric practice and borderline conditions in pediatric nephrology]. PMID- 3093972 TI - Electrical properties of Madin-Darby-canine-kidney cells. Effects of extracellular sodium and calcium. AB - In incompletely confluent Madin Darby canine kidney cells continuous measurements of the potential difference across the cell membrane (PD) were made with conventional microelectrodes during rapid changes of extracellular sodium and/or calcium concentration. During control conditions PD averages -50.6 +/- 0.7 mV. Reduction of extracellular sodium concentration from 131.8 to 17.8 mmol/l leads to a reversible hyperpolarization of the cell membrane to -65.3 +/- 1.1 mV. This hyperpolarization is not significantly reduced by omission of glucose or presence of amiloride (1 mmol/l) in the perfusates. Instead, 1 mmol/l amiloride depolarizes the cell membrane by +5.2 +/- 0.4 mV. 1 mmol/l barium depolarizes the cell membrane to -31.3 +/- 1.1 mV. Step increases of extracellular potassium concentration from 5.4 to 10 and 20 mmol/l depolarize the cell membrane by +5.5 +/- 0.5 mV and +16.5 +/- 1.8 mV respectively. In the presence of barium, the depolarizing effect of increasing extracellular potassium concentration and of amiloride is almost abolished. Reduction of extracellular sodium concentration in the presence of barium, however, leads to a transient hyperpolarization of the cell membrane. During this transient hyperpolarization, increasing extracellular potassium concentration depolarizes the cell membrane despite the continued presence of barium. Omission of extracellular calcium (EDTA) depolarizes the cell membrane by +36.7 +/- 3.2 mV. In the absence of extracellular calcium, the hyperpolarizing effect of reduced extracellular sodium concentration is markedly reduced (-4.5 +/- 1.2 mV). 2 mumol/l A23187 in the presence of extracellular calcium hyperpolarizes the cell membrane to -72.5 +/- 0.6 mV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3093974 TI - Amalgam of nursing acuity, DRGs, and costs. PMID- 3093975 TI - Predicting nursing care costs with a patient classification system. PMID- 3093973 TI - Phenothiazines increase active sodium transport across the isolated toad skin. AB - Fluphenazine (FPZ) and trifluoperazine (TFP) are phenothiazine derivatives commonly used as antipsychotic tranquilizers. Their mechanism of action is incompletely understood. Epidermal addition of each drug promoted biphasic short circuit current (SCC) changes across isolated pelvic skin of Bufo arenarum toads. By means of radiotracers fluxes, SCC was found to be given by the algebraic sum of net sodium and chloride transport. A readily stimulant effect was detected a low concentrations (from 1 X 10(-6) mol/l up to 1 X 10(-4) mol/l for FPZ, from 1 X 10(-5) mol/l up to 3.2 X 10(-4) mol/l for TFP) above which inhibition prevailed. Dermal FPZ also stimulated SCC. A higher concentration and time threshold were required. Epidermal 1 X 10(-5) mol/l FPZ stimulation was partially reversible, with a diminished membrane resistance and enhancement of sodium influx, without alteration of sodium efflux or net chloride transport. It could be prevented by amiloride pretreatment, or diminished by dermal sodium removal. Variation of epidermal bulk pH from 5.8 to 8.7 demonstrated that ionized and nonionized molecules contribute to FPZ's effect. Our results suggest that SCC stimulation elicited by FPZ and TFP may be a consequence of direct or indirect modifications on apical sodium conductance. PMID- 3093976 TI - Determining the cost of nursing care within DRGs. PMID- 3093977 TI - Severity of illness and nursing intensity as predictors of treatment costs. PMID- 3093978 TI - Determining nursing costs: the Nursing Intensity Index. PMID- 3093979 TI - Building a base for management of costs: a research program. PMID- 3093980 TI - The credibility of patient classification instruments. PMID- 3093981 TI - Comorbidity and length of stay: a case study. PMID- 3093982 TI - The cost-quality tradeoff in productivity management. PMID- 3093983 TI - Where do we go from here? PMID- 3093984 TI - Using the warp concept of graphics in patient classification. PMID- 3093986 TI - Correlating patient classification and DRGs. PMID- 3093987 TI - Relationships among nursing care requirements, nursing resources and charges. PMID- 3093985 TI - Patient management categories and the costs of nursing services. PMID- 3093988 TI - An E. coli beta-galactosidase cassette suitable for study of eukaryotic expression. PMID- 3093991 TI - Oral penicillin therapy for thoracic actinomycosis. PMID- 3093989 TI - Finding the facts on glyceryl trinitrate tablets. PMID- 3093990 TI - C-reactive protein in acute otitis media. AB - This study was designed to explore whether C-reactive protein (CRP) in serum is helpful in assessing the etiologic diagnosis of acute otitis media (AOM) in children. CRP was measured serially by a radial immunodiffusion method in sera from 67 children with AOM and in 67 matched controls, affected by noninfectious neurologic disorders. In the study group 43 (64%) children had a confirmed bacterial AOM and 24 (36%) showed no bacterial growth from middle ear fluid. The upper limit of CRP in controls was 15 mg/liter. Concentrations of CRP in patients with bacterial AOM ranged from less than 6 to 150 mg/liter; in 71% of the cases the value was greater than 15 mg/liter. In the patients with sterile middle ear fluid CRP ranged from less than 6 to 110 mg/liter; in 67% of the cases the level was greater than 15 mg/liter. CRP greater than 15 mg/liter showed sensitivity of 72%, specificity of 33%, predictive value of a positive test of 66% and predictive value of a negative test of 40%, in detecting bacterial AOM. Measurement of CRP should not be used in the decision regarding antimicrobial therapy for AOM in children. PMID- 3093993 TI - [Cost analysis of the treatment of peptic ulcer at a regional internal disease outpatient clinic, gastrological specialty dispensary and surgical clinic]. PMID- 3093992 TI - Infection due to penicillinase-producing Neisseria gonorrhoeae in a sexually abused girl. PMID- 3093994 TI - [Fetal transfusion in Rh incompatibility: its evaluation after 16 years' use]. PMID- 3093995 TI - Synthesis and some reactions of 2-cyanomethylimidazo [4,5-b]pyridine. Tuberculostatic investigations of obtained compounds. AB - 2-Cyanomethylimidazo [4,5-b]pyridine 1 was obtained and its properties during acid and basic hydrolysis, esterification, and reaction with hydrogen sulfide were investigated. Condensation of 1 with aromatic aldehydes was also studied. Some of the obtained compounds were tested on tuberculostatic activity. PMID- 3093996 TI - Emergency care or convenience care. Providers may have to choose one hat. PMID- 3093997 TI - Survival after severe self poisoning with sodium valproate. AB - A 48 year old patient deliberately poisoned herself with 25 g of sodium valproate and survived with supportive measures only. This case contradicts the experience of those who advocate aggressive management of such severe overdoses. PMID- 3093998 TI - [Dopamine in the pathogenesis of normogonadotropic amenorrhea]. AB - A total of 108 patients with normo-gonadotropic amenorrhea and 25 normal females were investigated. Three dopamine-dependent parameters were under study: maximum range of changes in the blood levels of luteinizing hormone (LH) and follicle stimulating hormone, hypophyseal response to thyrotropin releasing factor (TRF) and prolactinemia-dependent therapeutic effect of bromocriptine. Significantly increased range of the serum gonadotropin levels, increased reaction of hypophyseal thyrotropic hormone to TRF and higher therapeutic efficiency of bromocriptine was revealed in hyperprolactinemic patients versus those with normo gonadotropic amenorrhea. The results obtained are indicative of the decreased dopaminergic tension of the tuberoinfundibular system in hyperprolactinemic amenorrhea and increased one in normoprolactinemic patients. In 15 out of 32 normoprolactinemic patients bromocriptine therapy normalized their menstrual cycles. The range of spontaneous changes in the blood levels of LH was supposed to be a prognostic criterion for the assessment of bromocriptine therapeutic efficiency. A relative hypophyseal deficiency of dopamine was suggested in some of normoprolactinemic patients. PMID- 3093999 TI - [Diagnostic value of the luliberin test with patients with polycystic ovaries]. AB - Gonadotropic function was investigated and the diagnostic value of the test with luteinizing hormone releasing factor (LHRF) was assessed in patients with polycystic ovaries. For this purpose a 100 micrograms dose of LHRF was intravenously jet injected to 10 patients with nonspecific polycystic ovaries. Levels of luteinizing and follicle stimulating hormones (LH and FSH) were determined before the injection and 15, 30, 60, 90 or 120 minutes after it. Patients with nonspecific polycystic ovaries compared with those who had specific pattern of the disease or with normal women showed elevated basal LH levels which significantly increased in response to LHRF administration. In patients with specific form of the disease the FSH response to the injection was inhibited while LN basal levels as well as its response to LHRF were the same as in healthy women. In 13 out of 15 patients (3 out of 4 amenorrheic females among them) the preparation displayed its ovulatory affect after a single diagnostic dose. Desirability of LHRF use for a differential diagnosis of polycystic ovaries or for therapeutic stimulation of ovulation was suggested. PMID- 3094000 TI - [Role of thyroxine in releasing tissue plasminogen activators]. AB - Experiments on animals have shown that thyroxin at doses of 10, 50 and 150 micrograms/kg promotes releasing the plasminogen tissue activator from the kidneys, liver and heart. It leads to an increase in the difference in its content in the venous and arterial blood of these organs as compared to control animals. Thyroxin at the above doses simultaneously decreases the level of the plasminogen activator in the pulmonary, renal and liver tissue as well as in the myocardium. PMID- 3094001 TI - [Clinical and bacteriological aspects of the drug resistance of Mycobacterium tuberculosis in patients with chronic destructive pulmonary tuberculosis]. PMID- 3094002 TI - [Effectiveness of the method of electrophoretic concentration of Mycobacteria]. PMID- 3094003 TI - [Biological properties of drug-sensitive Mycobacterium tuberculosis]. PMID- 3094004 TI - DNA sequence adjacent to and specific for the 1.672 g/cm3 satellite DNA in the Drosophila genome. AB - The Drosophila genome contains nearly 2.8 X 10(4) kilobases of satellite DNA. This simple sequence satellite DNA is contained within transcriptionally inactive heterochromatin that is distributed among all chromosomes with a concentration at the centromeres and along the length of the Y chromosome. To investigate the relationship of the satellite DNA with the surrounding sequences, we have isolated a satellite junction sequence that is repetitive and specifically adjacent to the 1.672 g/cm3 satellite DNA. It is conserved between strains of Drosophila melanogaster and localized to the chromocenter of polytene chromosomes. The characteristics of this sequence suggest a functional role involving the specific organization of large regions of chromosomes. PMID- 3094005 TI - Islet-activating protein inhibits leukotriene D4- and leukotriene C4- but not bradykinin- or calcium ionophore-induced prostacyclin synthesis in bovine endothelial cells. AB - Incubation of the bovine endothelial cell line, CPAE, with leukotriene D4, leukotriene C4, bradykinin, or the calcium ionophore A23187 results in the release of arachidonic acid metabolites including 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin. Pretreatment of these cells with the pertussis toxin islet-activating protein (IAP) results in a dose-dependent inhibition of the release of arachidonic acid metabolites and prostacyclin in response to leukotriene D4 and leukotriene C4. In contrast, similar responses evoked by bradykinin or ionophore were not significantly altered by the IAP pretreatment of the cells. IAP in the presence of [32P]NAD specifically [32P]ADP ribosylates a 41-kDa protein in membranes prepared from CPAE cells. Pretreatment of the intact cells with IAP resulted in a dose-dependent inhibition of subsequent 32P labeling of the toxin substrate in the membranes and correlates with the uncoupling of the leukotriene responses. These results suggest that the 41-kDa IAP substrate, presumably a guanine nucleotide regulatory protein, mediates the response of CPAE cells to leukotriene D4 and leukotriene C4, but not to bradykinin or the calcium ionophore. PMID- 3094006 TI - Dispersal of the parasitic ciliate Lambornella clarki: implications for ciliates in the biological control of mosquitoes. AB - Lambornella clarki (Ciliophora: Tetrahymenidae), an endoparasite of Aedes sierrensis (Diptera: Culicidae), is dispersed by infected adult mosquitoes. Invasion of the ovaries induces parasitically castrated females to exhibit oviposition behavior and thereby actively disperse ciliates through deposition into water. Oviposition behavior of infected females is prolonged and mimics that of normal gravid females in their first gonotropic cycle. Adults of both sexes also passively disperse ciliates by dying on water surfaces, and infected adults are more likely to die on water than uninfected adults. Ciliates dispersed by infected adults can infect larvae and form desiccation-resistant cysts. Parasite induced dispersal by hosts, desiccation-resistant cysts, an active host-seeking infective stage, and high infection and mortality rates all indicate significant biological control potential for these and related ciliates against container breeding mosquitoes. PMID- 3094007 TI - Assignment of the human and mouse prion protein genes to homologous chromosomes. AB - Purified preparations of scrapie prions contain one major macromolecule, designated prion protein (PrP). Genes encoding PrP are found in normal animals and humans but not within the infectious particles. The PrP gene was assigned to human chromosome 20 and the corresponding mouse chromosome 2 using somatic cell hybrids. In situ hybridization studies mapped the human PrP gene to band 20p12--- pter. Our results should lead to studies of genetic loci syntenic with the PrP gene, which may play a role in the pathogenesis of prion diseases or other degenerative neurologic disorders. PMID- 3094008 TI - AKR murine thymic leukemias are from a distinct thymic cell lineage and do not express the beta chain of the T-cell antigen receptor. AB - Characterization of tumors that arise spontaneously in the AKR mouse indicates that they are derived from cells of a distinct T-cell lineage. Cells in this subclass bear surface antigens, designated Tpre, Tthy, Tind, and Tsu, which are encoded by genes in the Tsu linkage group on murine chromosome 12. We have examined the rearrangement and expression of genes encoding the T-cell alpha, beta, and gamma chains in these tumors. Although these cells contain alpha-chain mRNA, they do not produce a normal-sized beta-chain mRNA. Most of them also lack gamma-chain mRNA. Each thymic leukemia was derived from a cell arrested at a different stage of development as defined by their expression of terminal deoxynucleotidyl transferase and Thy-1 mRNA. The data presented here are consistent with a model in which thymocytes expressing Tpre, Tthy, Tind, or Tsu undergo somatic development parallel to the development of other T cells. However, these thymocytes do not appear to differentiate into cells bearing alpha beta heterodimers of the T-cell antigen receptor. PMID- 3094009 TI - Presence of preactivated T cells in hemodialyzed patients: their possible role in altered immunity. AB - Interleukin 2 (IL-2) and B-cell growth factors I and II (BCGF I and BCGF II) are lymphokines produced by T cells that play a major role in T- and B-cell cooperation. Peripheral blood lymphocytes from 12 uremic patients undergoing intermittent hemodialysis were tested for their capacity to produce IL-2 and BCGFs and to respond to these soluble mediators. IL-2 and BCGF activities were determined by means of two biological assays (proliferation of IL-2-dependent cytotoxic T-cell line CTLL-2 and of anti-human IgM (mu chain)-stimulated normal B cells, respectively) in the supernatants of phytohemagglutinin A-stimulated T cell cultures. IL-2 activity was significantly decreased in patients as compared to normal controls (mean +/- SEM, 0.28 +/- 0.09 unit per ml) in hemodialyzed patients versus 1.02 +/- 0.16 units per ml in normal controls). This profound abnormality contrasted with the normal activity of the BCGFs that was invariably observed in the same supernatants. A similar dissociation was detected when analyzing the sensitivity of uremic B and T cells to exogenous purified lymphokines. Anti-IgM (mu chain)-stimulated uremic B cells exhibited a normal response to recombinant IL-2 and to chromatography-purified BCGF I and BCGF II. Resting B cells did not show any increased reactivity to these lymphokines. In contrast, whereas in normal controls recombinant IL-2 exclusively induced the proliferation of T cells that had been previously activated by a mitogen, resting T cells from uremic patients were highly responsive to exogenous IL-2. This abnormal response was paralleled by significantly increased proportions of peripheral T cells recognized by the anti-Tac monoclonal antibody that specifically binds to the IL-2 receptor. These data clearly show the existence in hemodialyzed patients of abnormally high proportions of T cells presenting phenotypic and functional signs of preactivation. This increased T-cell IL-2 receptor expression may offer an explanation to the deficient IL-2 activity observed in patients' supernatants (by inducing increased absorption of the lymphokine). The potential relevance of these preactivated T cells to the depressed cell-mediated immunity observed in hemodialyzed patients is outlined. PMID- 3094010 TI - Monoclonal antibody specific for an activated RAS protein. AB - Activated RAS transforming genes that encode proteins (p21s) with amino acid substitutions at positions 12, 13, or 61 have been detected in 10-20% of human neoplasms. This report describes a monoclonal antibody (DWP) raised against a synthetic peptide corresponding to amino acids 5-16 of a mutated RAS gene encoding Val instead of Gly at position 12. DWP reacted in competition assays with peptides containing Val or Cys at position 12, but did not react with peptides containing Gly, Arg, Ser, Ala, Asp, or Glu at position 12. Immunoblot analysis of transformed NIH cells and human carcinoma cell lines showed that DWP reacts specifically with activated RAS proteins containing Val at position 12 and not with normal p21s or p21s activated by other amino acid substitutions at positions 12 and 61. Immunohistochemical studies showed that DWP-labeled transformed NIH cells and human carcinoma cells contained p21s with either Val or Cys at position 12 but not normal or other activated p21s. In contrast to the specificity seen with human carcinoma cell lines, analysis of formalin-fixed, primary carcinoma specimens indicated that positive immunoperoxidase staining with DWP did not necessarily correlate with immunoblot and transfection assays for the presence of activated RAS proteins. Immunohistochemical studies did show, however, that DWP preferentially binds human carcinoma cells. PMID- 3094011 TI - Nucleotide sequence of the mRNA encoding the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) from the chicken. AB - We have determined the sequence of the mRNA encoding cytosolic phosphoenolpyruvate carboxykinase (GTP) [GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32] from the chicken and have deduced the primary structure of the protein. The message for the enzyme is 2762 bases long and encodes a protein of 622 amino acids with a molecular mass of 69,522 daltons. The 5' untranslated region is 246 nucleotides long and contains two nonfunctional AUG initiator codons. The 3' untranslated sequence is 649 bases long and contains multiple polyadenylylation signals. There are regions of dyad symmetry and an A + U-rich region within the 3' translated and untranslated sequences of the message. Such regions are also present in the mRNA for the enzyme from the rat and may be of functional significance. Conserved regions of the enzyme, that may interact with substrates, were identified by comparing the amino acid sequence of phosphoenolpyruvate carboxykinase with that of other proteins that use guanine nucleotides and phosphoenolpyruvate as substrates. PMID- 3094012 TI - Molecular cloning and characterization of cDNA encoding the GTP-binding protein alpha i and identification of a related protein, alpha h. AB - We have cloned and characterized cDNA encoding alpha i, the GTP-binding subunit of Gi, a protein that mediates hormonal inhibition of adenylate cyclase and hormonal regulation of other membrane functions. We have also identified cDNA encoding a putative protein, which we have named alpha h, that is highly homologous to alpha i but different from other known GTP-binding proteins. Both cDNAs were isolated from a bovine pituitary library. The cDNA encoding alpha i was identified by finding that the amino acid sequence determined for two tryptic peptides from alpha i agreed exactly with amino acid sequences deduced from the cDNA. We also determined the amino acid sequence of peptides derived from alpha o, a related 39-kDa protein purified from bovine brain. These sequences are approximately 75% identical to the sequence determined for alpha i. Southern blot analysis of bovine genomic DNA, using as probes radiolabeled cDNAs for alpha i, alpha h, and the alpha subunit of a related protein, transducin, showed that each probe recognized different genomic DNA fragments. Our results suggest a further level of complexity in the organization of the G-protein gene family, with multiple G proteins of very similar structural properties likely to be identified as products of distinct genes. PMID- 3094013 TI - Activation of complement by immunoglobulin M is impaired by the substitution serine-406----asparagine in the immunoglobulin mu heavy chain. AB - We have isolated and analyzed the DNA encoding the mu heavy chain constant region of a mutant IgM that is defective in initiating complement-dependent cytolysis. By assaying the expression of mu-chain genes that were constructed in vitro from mutant and wild-type gene segments, we have mapped the mutation into a 555-base pair segment that spans part of the third and fourth constant region domains. In this segment there is one nucleotide change, such that the mutant mu-chain gene encodes asparagine rather than the normal serine at amino acid position 406 in the third constant domain. We have used site-directed mutagenesis to introduce a comparable mutation into the normal mu-chain gene and confirmed that this substitution causes the production of IgM with the original mutant phenotype. Evidence is also provided that the serine-406----asparagine substitution might cause the mutant mu chain to be abnormally glycosylated. PMID- 3094014 TI - Complete amino acid sequence of human thyroxine-binding globulin deduced from cloned DNA: close homology to the serine antiproteases. AB - Antibodies directed against thyroxine-binding globulin (TBG) have been used to screen a human liver lambda gt11 expression library. A 1.46-kilobase clone was identified which encodes nearly the complete amino acid sequence, beginning at amino acid 17 of the mature protein. To complete the protein sequence, the cDNA clone was used to identify a genomic clone coding for TBG in a human X chromosome library. The overlapping recombinant clones contained an open reading frame coding for 415 amino acids followed by a polyadenylylation signal (AATAAA) located 275 nucleotides from a TAG termination codon. Beginning at residue 21, the deduced amino acid sequence agrees closely with the known NH2-terminal sequence of the mature peptide. The preceding 20 amino acid residues are hydrophobic in character and presumably represent a leader sequence. Four glycosylation sites were identified, corresponding to the number determined for the purified protein. DNA blot hybridization revealed a single-copy gene, which by chromosomal analysis was found to be located on the long arm of the X chromosome. Unexpectedly, the nucleotide sequence of TBG is closely homologous to those encoding the plasma serine antiproteases alpha 1-antichymotrypsin and alpha 1-antitrypsin. However, there is little overall homology between TBG and transthyretin (prealbumin), the other major thyroxine-binding protein of human plasma. PMID- 3094015 TI - Isolation of the origin of replication associated with the amplified Chinese hamster dihydrofolate reductase domain. AB - Autoradiography of restriction digests of DNA labeled in early S phase indicates that replication of the amplified dihydrofolate reductase (DHFR) domain of methotrexate-resistant CHOC 400 cells initiates within a 6.1-kilobase pair (kb) EcoRI-doublet located on the 3' side of the DHFR gene. To localize the DHFR origin fragment, synchronized CHOC 400 cells were either pulse labeled with [3H]thymidine in vivo or permeabilized and incubated with [32P]dATP under conditions that support limited chromosomal DNA replication. The temporal order of replication of amplified fragments was determined by hybridization of the in vivo or in vitro replication products to cloned fragments spanning the earliest replicating portion of the DHFR domain. At the G1/S boundary, the labeled products derived from the replication of amplified sequences, either in whole or permeabilized cells, are distributed about an amplified 4.3-kb Xba I fragment that maps 14 kb downstream from the DHFR gene. As cells progress through the S phase, bidirectional replication away from this site is observed. These studies indicate that the 4.3-kb Xba I fragment contains the origin of replication associated with the amplified DHFR domain. PMID- 3094016 TI - Functional antibody lacking a variable-region disulfide bridge. AB - In 1981, Auffray et al. [Auffray, C., Sikorav, J. L., Ollo, R. & Rougeon, F. (1981) Ann. Immunol. (Inst. Pasteur) 132D, 77-88] reported a partial cDNA sequence of the heavy chain from the ABPC48 plasmacytoma whose protein product had previously been shown to bind bacterial and grass levan. In the cDNA sequence the second half-cystine of the heretofore invariant disulfide bridge had been replaced by a tyrosine. Since the presence of invariant variable-region disulfide bridges has been considered a basic structural feature of the antibody molecule necessary for proper folding and function, we have analyzed the heavy chain protein produced by ABPC48. Our results indicate that heavy chains from ABPC48 quantitatively express tyrosine in place of the normally occurring second half cystine in the variable region. Furthermore, this antibody population is capable of both binding antigen and subsequent precipitation. Thus, the presence of a disulfide bridge in the heavy-chain variable region does not appear necessary for proper function of this antibody and may not be obligatory for antibody function in general, as has been assumed previously. PMID- 3094017 TI - Lymphokine-activated killer cells targeted by monoclonal antibodies to the disialogangliosides GD2 and GD3 specifically lyse human tumor cells of neuroectodermal origin. AB - Monoclonal antibodies 14.18 (IgG3) and 11C64 (IgG3) directed against disialogangliosides GD2 and GD3, respectively, when used in conjunction with human peripheral blood mononuclear cells (PBMCs) stimulated with human recombinant interleukin (rIL-2) lyse both human melanoma and neuroblastoma cells by antibody-dependent cellular cytotoxicity. Such monoclonal antibody-"armed" effector cells are specifically directed to targets expressing the given disialoganglioside without detectable cross-reactivity. In addition, antibody dependent cellular cytotoxicity as well as the natural killing ability of human PBMCs is augmented by a brief coincubation with rIL-2. PBMCs augmented by rIL-2 and armed with monoclonal antibodies significantly suppressed tumor growth in the xenotransplant nude mouse model. Our results suggest that once a threshold level of activation of PBMCs is achieved, additional rIL-2 (over three orders of magnitude of concentration) does not significantly enhance cytolytic augmentation. Furthermore, anti-GD3 monoclonal antibody 11C64 together with rIL-2 stimulated PBMCs from melanoma patients with widely differing tumor burdens effectively lyse melanoma tumor targets in antibody-dependent cellular cytotoxicity. Our results also suggest that GD2 and GD3 represent distinct and relevant immunotherapeutic target structures on melanoma whereas GD2 does the same for neuroblastoma tumors. Our data suggest that targeting of activated human effector cells may provide a new and effective cancer immunotherapy protocol. PMID- 3094018 TI - Hydrolase activities increase in the rat aorta with growth and aging but not in liver and kidney. AB - We examined specific activities (based on DNA) of six glycosidases and cathepsin C in aorta, kidney, and liver from male rats of 2, 6, 10, and 14 months of age. The premise was that assessing cellular catabolism of arterial and nonvascular tissues over age might more fully clarify the impact of age (and growth) alone upon vascular wall metabolism. All aortic glycosidases increased significantly (P less than 0.05) over the holding period as follows: neutral alpha-glucosidase, up 93%; beta-galactosidase, up 102%; N-acetyl-beta-glucosaminidase, up 119%; alpha mannosidase, up 77%; beta-glucuronidase, up 65%; acid alpha-glucosidase, up 95%. Cathepsin C specific activity was unchanged as was aortic DNA content; total protein content increased 136%. In the kidney, all glycosidase specific activities declined over age with decreases ranging 39-55%; cathepsin C was unchanged. In the liver, neutral alpha-glucosidase increased 12%, acid alpha glucosidase was unchanged, and the four remaining glycosidases decreased an average of 5-35% by 14 months of age. Liver cathepsin C decreased 44% over this period. Thus, enhancement of hydrolase baseline activities prevails during growth and aging in rat aortic tissue whereas hydrolases of kidney and liver tissues generally decline. PMID- 3094019 TI - Liver scarring induced by polychlorinated biphenyl administration to mice previously treated with diethylnitrosamine. AB - Exposure of mice for 8 weeks to drinking water containing diethylnitrosamine (DEN) was accompanied by alterations in hepatocyte structure and varying degrees of liver nonparenchymal cell (NPC) proliferation. Eighteen and a half weeks after cessation of DEN exposure, there was a 47% incidence of hepatocellular nodules. Centrilobular hepatocyte hypertrophy occurred consistently in mice given intraperitoneal injections of the polychlorinated biphenyl (PCB) mixture Aroclor 1254. PCB administration to mice previously treated with DEN was not accompanied by increases in gross liver nodule incidence above that induced by DEN, but many more developing microscopic nodules within the liver were observed in DEN-treated mice given Aroclor 1254 than in mice treated only with DEN. Aroclor 1254 administration over a 16-week period to mice previously treated with DEN was accompanied by an 83% incidence of severe distortion of liver structure resulting from nodule formation, uneven patterns of hepatocyte growth, and extensive deposition of scar tissue containing proliferating bile ducts. Morphological evidence of intestinal metaplasia was observed in proliferating bile duct-like structures during an early stage of liver adenofibrosis. PMID- 3094020 TI - Para osteo arthropathy--ectopic ossification of healing tendon about the rodent ankle joint: histologic and type V collagen changes. AB - Ectopic bone formation, or para osteo arthropathy (POA), is commonly seen in humans following lesions to the central nervous system. The condition also occurs after severe trauma, burns, or tetanus, and, rarely, after poliomyelitis or cauda equina lesions. The lack of a suitable laboratory animal model has hampered study of its etiology and treatment. The lesion occurs just above the rodent ankle joint 7 weeks after repair of the severed achilles tendon. Tendon repair using a single silk suture resulted in ectopic calcification in 22 of 23 animals. Ectopic ossification, with extensive mineralization, occurred in 11 animals, 5 of which showed bone marrow. Ectopic mineralization was moderate in 8 others, minimal in 4, and absent in one. Collagen typing thrice during healing indicated that type V collagen increased by one-third at 10 days, doubled at 20 days, and returned to near normal amounts at 50 days. Since type V collagen is a major component of the nonfibrous collagen of blood vessels, increased amounts of type V collagen are consistent with the presence of many new blood vessels in the granulation tissue at 10 and 20 days. Vascularity is less dense at 50 days when ectopic mineralization and new bone formation are observed. These findings suggest that POA and the degree of maturation of healing tendon may be linked to reduced amounts of type V collagen. It is concluded that the sutured tendon of the rodent ankle joint offers an animal model by which to study ectopic bone formation, or para osteo arthropathy. PMID- 3094021 TI - Increased ionic strength: effects on DNA fragmentation and poly(ADP-ribose) polymerase activity in HeLa nuclei. AB - Poly(ADP-ribose) polymerase activity was measured in a crude nuclear fraction isolated from HeLa cells. It was found that the addition of ammonium sulfate or other salts to the standard incubation medium inhibited the formation of poly(ADP ribose). Through the use of alkaline sucrose density gradients it was also noted that this same increase in ionic strength inhibited the in vitro breakdown of the HeLa DNA. Additional experiments with alkaline sucrose density gradients and deoxyribonuclease I showed that the in vitro activity of poly(ADP-ribose) polymerase is largely dependent upon DNA fragmentation but that DNA fragmentation at least in vitro is not dependent upon the formation of poly(ADP-ribose). These observations imply that this nuclear enzyme is not extremely sensitive to changes in the ionic strength of the reaction media but is affected indirectly, supposedly through changes in the endonuclease activity of the HeLa nuclei. If this proves to be true, then the addition of salt to the incubation medium for poly(ADP-ribose) polymerase could prove to be a valuable tool for the study of ADP-ribosylation reactions. PMID- 3094023 TI - Molecular evidence on the ape subfamily homininae. PMID- 3094022 TI - Pesticide residues in foods. PMID- 3094024 TI - Stochastic errors in DNA evolution and molecular phylogeny. PMID- 3094025 TI - Symposium on lipoxygenase products and polyunsaturated fatty acids. Limoges, October 1985. PMID- 3094026 TI - In vitro effects of aspirin and non steroidal anti-inflammatory drugs on the formation of 12-hydroxyeicosatetraenoic acid by platelets. AB - The in vitro effects of aspirin and other non steroidal antiinflammatory drugs (NSAIDs) on 12-HETE formation were evaluated in platelet rich plasma (PRP) stimulated with collagen. Aspirin (1 X 10(-4)-1 X 10(-3) M) inhibited 12-HETE production in PRP. Inhibition of 12-HETE formation was detected also in PRP incubated with indomethacin and BW 755C. Sodium salicylate, instead, did not reduce 12-HETE synthesis. Aspirin (3 X 10(-3) M) did not modify 12-HETE synthesis in similarly challenged washed platelet (WP) preparations, inspite of its effect on the cyclooxygenase pathway. It may be concluded that aspirin and other NSAIDs, not only affect the cyclooxygenase pathway, but also inhibit 12-HETE synthesis. In addition it is shown that the 12-HETE synthesis is reduced by plasma and that this effect is enhanced in the presence of aspirin. PMID- 3094027 TI - Characterization of the arachidonate-containing molecular species of phosphoglycerides in the human neutrophil. AB - Neutrophils were labeled with high specific activity, [3H]-arachidonate and separated into their arachidonate-containing phosphoglycerides using a slight modification of the normal phase and reverse phase HPLC described by Patton et al. The individual molecular species of PC, PE and PI containing arachidonate were characterized by fast atom bombardment/mass spectrometry techniques. Eight major arachidonate-containing molecular species of PC, six major arachidonate containing molecular species of PE and two major arachidonate-containing molecular species of PI could be found. With the structures of the phosphoglycerides eluting from the reverse phase HPLC column known, general trends in the HPLC elution behavior of 1-0-alkyl, 1-alk-1-enyl and 1-acyl-2 arachidonoyl phosphoglycerides could be observed. PMID- 3094028 TI - Lipoxygenase metabolism of endogenous and exogenous arachidonate in leukocytes: GC-MS analyses of incubations in H2(18)O buffers. AB - Fatty acids are labeled with 18O in the carboxyl group during ester hydrolysis in H2(18)O. We utilized this principle to develop a novel mass spectrometric method for study of the turnover of arachidonic acid in intact cell systems. Analysis of 18O incorporations was by negative ion chemical ionization GC-MS. The use of deuterium-labeled exogenous substrates allowed the metabolic fate of exogenous and intrinsic compounds to be distinguished. Thus, it was shown that the preferred route of 5-lipoxygenase metabolism of exogenous arachidonic acid in ionophore-stimulated human neutrophils is via direct reaction with the enzyme and not via incorporation into cellular lipids. The re-uptake of 5-HETE was also studied. For investigation of intracellular reactions which involve ester hydrolysis, the 18O labeling method is unique in providing direct evidence of the intermediate metabolic pathway of endogenous and exogenous products associated with the arachidonic acid cascade. PMID- 3094029 TI - Positional specificity of lipoxygenases and their suitability for testing potential drugs. AB - Comparative studies on isolated lipoxygenases revealed the following features: variability of their positional specificity, diversity of enzymatic properties including sensitivity to inhibitors, a common general mechanism of action. The molecular basis of the positional specificity of lipoxygenases is discussed. The lipoxygenase of reticulocytes proved to be an excellent model in the search for inhibitors of the arachidonate 5-lipoxygenase. Reticulocyte lipoxygenase may form a wide spectrum of products belonging to all important classes of primary lipoxygenase metabolites hitherto known (HPETE's, diHPETE's, lipoxins, epoxyleukotrienes and others). This enzyme was used as basal test in a screening hierarchy for lipoxygenase-inhibitory antiasthmatic drugs and led to the discovery of new orally acting potential antiasthmatics. There was a high correlation between inhibition of reticulocyte lipoxygenase and antibronchoconstrictory activity with airway preparations in vitro and in vivo. PMID- 3094030 TI - Quality criteria for chromatographic analytical systems of polyunsaturated fatty acids metabolites. AB - The most powerful technique for eicosanoids identification is gas chromatography prior to mass spectrometry. Results are highly dependent upon the choice of appropriate gas chromatographic systems; the critical point of the system being the quality of the column. Our work is intended to provide a general overview of open tubular capillary columns which can be used for separation, identification and quantification of eicosanoids. PMID- 3094032 TI - Thromboxane A2 (TXA2) formation by washed human platelets under the influence of low and high density lipoproteins from healthy donors. AB - Low density lipoprotein (LDL) stimulates TXA2 formation (measured as malondialdehyde) in washed human platelets with active cyclooxygenase, whereas high density lipoprotein (HDL) does not show any influence on TXA2 formation in this system. These results support the hypothesis that the proaggregatory action of a high plasma LDL concentration may be mediated by modification in the biosynthesis of eicosanoids. The mode of action of lipoproteins is discussed. PMID- 3094031 TI - Eicosanoid regulation of oosporogenesis by Lagenidium giganteum. AB - Cell proliferation is inhibited in many biological systems by lipid peroxides and related products derived from polyunsaturated fatty acids. Using developmentally synchronized cultures of Lagenidium giganteum (Oomycetes: Lagenidiales), a facultative parasite of mosquito larvae, it has been documented that oxidative lipid metabolism is necessary for the induction and subsequent maturation of its sexual stage, the oospore. Addition of lipoxygenase inhibitors to liquid cultures of the fungus results in the stage-specific disruption of antheridial induction, gametangial fusion, induction of meiosis and spore cell wall formation. Oosporogenesis is inhibited by these compounds at concentrations which have no discernible effect on mycelial viability or asexual reproduction. Cyclooxygenase inhibition had comparable effects using ibuprofen and to a lesser extent with indomethacin. Phenylbutazone and the salicylates affected oosporogenesis only at concentrations which decreased asexual reproduction or mycelial viability. The inhibitory effects of NDGA on oosporogenesis could be reversed using partly purified eicosanoid extracts from growth media. PMID- 3094033 TI - Onion exerts antiaggregatory effects by altering arachidonic acid metabolism in platelets. AB - In vitro effects of an oily extract of onion were examined on the metabolism of arachidonic acid (AA) in human platelets. Onion was found to reduce the formation of thromboxane and lipoxygenase products from exogenous arachidonic acid in platelets; it did not inhibit the incorporation of AA into platelet phospholipids. While not affecting the platelet phospholipase activity it did reduce the formation of thromboxane B2 and lipoxygenase products in platelets that were prelabelled with arachidonic acid and then activated by A23187. This suggests that onion inhibits the formation of AA metabolites by exerting its effect at steps later than the liberation of AA. With concentrations of onion extract producing abolition of AA-induced aggregation, only partial inhibition of aggregation was observed with ADP- and epinephrine-induced aggregation. Onion did not inhibit A23187 induced aggregation. The results suggest that inhibition of platelet aggregation by onion is mediated largely by its effect on platelet thromboxane production. PMID- 3094034 TI - Pressor responses to arachidonic acid in pump-perfused sheep lungs. AB - The reported actions of arachidonic acid in the adult pulmonary circulation are controversial. Some authors reported that arachidonic acid causes only pulmonary vasoconstriction; others have found decreases in pulmonary vascular resistance with low-dose infusions. We have previously reported that arachidonic acid causes only pulmonary vasoconstriction in perinatal lambs during both normoxia and hypoxia. The effects of arachidonic acid on pulmonary vascular resistance were determined in adult sheep using an in situ pump-perfused left lower lung preparation. Arachidonic acid infusions (10.5-31.9 micrograms/kg . min) resulted in pulmonary vasoconstriction. The pulmonary vascular response to arachidonic acid was not altered by hypoxia or by infusion of PGF2 alpha. However, the pulmonary pressor response to hypoxia was increased by concomitant arachidonate infusions. Infusions of arachidonic acid during hypoxia resulted in systemic hypotension. Thus, pulmonary arachidonate metabolism appears to be unaffected by hypoxia or PGF2 alpha; however, hypoxia may enhance the formation of dilator PG's from the lung. PMID- 3094035 TI - Metabolism of arachidonic acid and synthesis of prostanoids in human endometrium and decidua. AB - Arachidonic acid metabolism and prostanoid synthesis were investigated using [14C]-arachidonic acid (AA) in human endometrium obtained at different phases of the ovarian cycle and decidua in early pregnancy. Prostaglandins (PG) identified in endometrium and decidua were PGE2 and PGF2 alpha. The capacity for the production of PGE2 and PGF2 alpha was higher in the secretory phase of endometrium than in the proliferative phase, and the maximum formation of PGE2 and PGF2 alpha was found in the mid secretory phase and in the late secretory phase, respectively. However, the production of PGs was markedly suppressed in decidua. On the other hand, more than 70% of [14C]AA was incorporated into total neutral lipids, whereas less than 22% was incorporated into glycerophospholipids in both endometrium and decidua. Secretory endometrium showed a higher uptake of [14C]AA into glycerophospholipids than did proliferative endometrium, whereas the incorporation into neutral lipids was lower in secretory endometrium than in the proliferative phase. Moreover, decidua showed a similar pattern of incorporation of [14C]AA to the proliferative phase. The changes of arachidonic acid metabolism and PG formation in both endometrium and decidua are discussed in terms of implantation and maintenance of early pregnancy. PMID- 3094036 TI - Parkinson's disease in the elderly: a long-term efficacy study of levodopa/benserazide combination therapy. AB - An open study was carried out in 60 elderly patients with Parkinson's disease to assess the efficacy and tolerance of long-term treatment with levodopa/benserazide combination therapy. Patients were treated for periods up to 2 years, doses being titrated to the lowest required to bring about adequate relief of symptoms. The mean daily dose ranged from 165 mg on entry to 199 mg in the 43 patients assessed at 24 months. The results showed that treatment provided lasting therapeutic benefits for approximately three-quarters of the study population with a low incidence of side-effects. PMID- 3094037 TI - Post-prostatectomy auto-irrigation with furosemide in the tropics. AB - A progressive study was carried out in 49 patients who underwent prostatectomy (10 transurethrally and 39 transvesically) to assess the effects of furosemide given intravenously for post-operative bladder irrigation. All 10 transurethral patients and 17 of the transvesical patients received furosemide, the remaining 22 patients receiving formal external bladder irrigation with saline. The results showed that post-operative infection was lowest and bed stay shortest in the patients with furosemide auto-irrigation. There was also less need for blood transfusion. No significant changes in haemoglobin and packed cell volume were observed in the transurethral patients; however, both decreased significantly in all 39 patients with transvesical prostatectomy, whether or not furosemide was used. Auto-irrigation with furosemide was found to be associated with a significant post-operative decrease in serum potassium but not in serum sodium levels. When external irrigation with saline was used, there was a significant increase in serum sodium. PMID- 3094038 TI - Destruction of noradrenergic innervation to the paraventricular nucleus: deficits in food intake, macronutrient selection, and compensatory eating after food deprivation. AB - Norepinephrine (NE) injected into the paraventricular nucleus (PVN) has a stimulatory effect on feeding behavior and is found to selectively enhance preference for carbohydrate in the rat. The present experiments were conducted to assess the impact of chronic depletion of NE within the PVN on food intake and appetite regulation. The catecholamine (CA) neurotoxin, 6-hydroxydopamine (6 OHDA), when administered into the PVN, produced a significant depletion of PVN NE in association with a variety of behavioral changes. The immediate consequence of the neurotoxin lesion was a dramatic increase in 24-hr food intake, attributed predominantly to a preferential increase in carbohydrate and fat consumption. The long-term effects related to CA depletion were a deficit in daily food consumption, particularly of carbohydrate (-42%). Although animals with diminished PVN NE maintained a normal diurnal feeding pattern, they failed to exhibit the increased ingestion of an energy-rich carbohydrate diet which rats normally show during the dark period of the diurnal cycle. Rats injected with 6 OHDA directly into the PVN exhibited a normal response to glucoprivic challenge, but demonstrated a deficit in their ability to produce compensatory feeding, particularly of carbohydrate and fat, in response to food deprivation. These findings suggest a specific function for PVN noradrenergic mechanisms in normal energy repletion when body energy stores are reduced. PMID- 3094039 TI - Dopamine-norepinephrine interactions in the development of hyperphagia and obesity following medial hypothalamic lesions. AB - Conflicting evidence exists on the ability of central 6-hydroxydopamine (6-OHDA) injections to alter the subsequent development of hyperphagia and obesity following medial hypothalamic lesions (MHL) in rats. An initial study found no effects of prior intracisternal (IC) 6-OHDA on the subsequent development of this MHL syndrome, while later work reported that a dopamine (DA) depletions induced by intracerebral 6-OHDA effectively blocked it. The present study reexamined this issue by investigating the effects of depleting brain dopamine, norepinephrine (NE), or both DA and NE, on overeating and obesity induced by subsequent MH lesions. Different patterns of DA and NE depletions were achieved by IC 6-OHDA in combination with systemic pretreatments designed to protect central NE, DA, or neither amine, respectively. It was found that 6-OHDA regimens that selectively depleted forebrain DA did prevent the development of hyperphagia and obesity following MHL. However, when such forebrain DA depletions were accompanied by NE depletions no such blockade occurred. Manipulations which selectively depleted forebrain NE had no effect on MHL-induced hyperphagia and obesity. These results offer a framework for resolving previous discrepancies in the literature concerning brain monoamines and MHL effects. They also indicate that the effectiveness of brain DA depletions in blocking the MHL syndrome is critically dependent on the functional status of NE systems. PMID- 3094040 TI - The effect of L-erythro-dihydroxyphenylserine injected into the lateral ventricle and the hypothalamus on the locomotor activity. AB - The effect of dihydroxyphenylserine (DOPS) on locomotor activity was studied using the Animex activity meter. One microgram of L-erythro-DOPS, a precursor of d-noradrenaline, was injected into the lateral ventricle once a day for one week or into the anterior hypothalamic area (AHA) once. After the intraventricular injection, the total locomotor activity (from 8:00 p.m. to 8:00 a.m.) of the rats injected with DOPS was significantly less than that of the rats injected with an artificial cerebrospinal fluid (5-ion). Analysis of the locomotor activity in consecutive 2-hr periods showed that the activity of the DOPS group during the time intervals of 10 p.m.-12 a.m., 12 a.m.-2 a.m. and 2 a.m.-4 a.m. was significantly less than that of the control group. After injection of DOPS or 5 ion into AHA, the total activity of the DOPS group was significantly less than that of the control. Analysis of the activity of the DOPS group for each 2-hr period between 10 p.m.-4 a.m. was also significantly less than that of the control. On the basis of these findings, the effect of DOPS in the brain noradrenergic system are discussed. PMID- 3094041 TI - Phorbol 12-myristate 13-acetate induces prolactin secretion from rat anterior pituitary gland by the activation of protein kinase-C. AB - The purpose of this study was to characterize the action of phorbol 12-myristate 13-acetate (PMA), a tumor-promoting agent, on rat anterior pituitary gland, focusing the attention on prolactin secretion. PMA elicited a significant increase in prolactin secretion without affecting phosphatidylinositol turnover, considered as an early post-receptor event controlling PRL secretion. However incubation of anterior pituitary glands with PMA caused a loss of protein kinase C activity in cytoplasm concomitant with an increased enzyme activity in the membrane. The action of PMA on prolactin secretion seems to be mainly dependent from the redistribution and activation of protein kinase-C. In fact, the phorbol ester did not affect pituitary cAMP and cGMP metabolism either in basal conditions or after theophylline. PMID- 3094042 TI - Plasma and tissue levels of flecainide in rats. AB - The time-courses of flecainide plasma and tissue levels were studied in Wistar male rats after i.v. administration (4 mg/Kg). Drug assay in plasma and tissue was performed with a specific and accurate HPLC technique. The final half lives in plasma and tissues were about 4 hours, except in the brain where the half life value was 9.8 hours. The mean tissue/plasma (T/P) ratios in myocardial, kidney, liver, skeletal and muscle tissues were 9.11, 13.8, 14.37, 6.31 respectively, while in the brain the T/P ratio rose progressively over the sampling time to 10.0. These data suggest that flecainide may accumulate in the central nervous system during prolonged treatment. Flecainide levels in adipose tissue were very low. Finally, there was an early "bulge" in the concentration curve, possibly reflecting enterohepatic circulation or non-linear elimination kinetics. PMID- 3094044 TI - Synthesis of 1,4-bis (3-oxo-1-alkenyl)benzene and the growth of Tetrahymena pyriformis. PMID- 3094043 TI - [Simultaneous and sequential inhibition of the arachidonic acid cascade by inhibitors of phospholipase A2, cyclooxygenase and lipoxygenases in carrageenan edema and adjuvant arthritis in the rat]. AB - According to the aim of the simultaneous and sequential inhibition of key enzymes of the arachidonic acid cascade, combinations of inhibitors of the phospholipase A2 (PLA2), cyclooxygenase (COX) and of lipoxygenases (LOX) were administered to rats with carrageenin edema and adjuvant arthritis, respectively. While the COX inhibitors diclofenac-Na and acetylsalicylic acid in combination with PLA2 and LOX inhibitors mostly gave overadditive antiinflammatory effects in the carrageenin edema, phenylbutazone in combination at most displayed additivity. Admixture of ascorbic acid led to subadditive effects. In the adjuvant arthritic rat, the combined administration of diclofenac-Na and dexamethasone yielded additive effects, only. The same result is valid for the combination of piroxicam and a LOX inhibitor in this model. Results are discussed with respect to the mode of action of substances as well as to the model peculiarities. PMID- 3094045 TI - Stopping power data for high-energy photon beams. AB - Spencer-Attix stopping power ratios for the dosimetry of high-energy photon beams used in radiation therapy have been calculated using the Monte Carlo method. The stopping power ratios are calculated in a more consistent way than previously and are given as a function of the attenuation properties of the beam. The dependence of the stopping power ratio on the electron contamination of the beam as well as on depth and field size has also been investigated. Results are compared with stopping power ratios recommended in different dosimetry protocols and to experimental results. The agreement with most dosimetry protocols is within about one per cent and with recent experimental data is better than half a per cent. PMID- 3094046 TI - Increasing role of economic analysis in the health care industry. AB - As the health care industry continues to absorb an ever-larger portion of society's resources, increasing pressure is being placed on the industry to justify its decisions about the outcomes of the services it renders relative to their costs. Emphasis is being shifted from accessibility to and availability of health care to the cost-effective delivery of those services. This focus on cost effectiveness is creating intense pressure on the various segments of the industry to justify their existence as cost-effective providers of services. To demonstrate cost effectiveness, the various segments are searching for tools to assist them. In this article, an outline of a mechanism for evaluating the cost effectiveness of providing physical therapy services is presented. PMID- 3094047 TI - Studies on the activities of tannins and related compounds; VIII. Effects of geraniin, corilagin, and ellagic acid isolated from geranii herba on arachidonate metabolism in leukocytes. PMID- 3094048 TI - Does maintenance lithium therapy prevent recurrences of mania under ordinary clinical conditions? AB - Mental-hospital admission rates in Edinburgh for mania, schizophrenia and psychotic depression were studied from 1970 to 1981, a 12-year period during which long-term lithium therapy was increasingly employed in affective illnesses. If this treatment had been effective admission and readmission rates for mania, and perhaps also for depression, should have fallen progressively. In fact, they rose steadily, while the admission rate for schizophrenia fell. These changes could not easily be attributed to changing diagnostic criteria, to the admission of milder affective illnesses, or to poor and deteriorating lithium surveillance. Their explanation is uncertain, but they cast some doubt on the efficacy of lithium prophylaxis in ordinary clinical practice. PMID- 3094049 TI - Performance effects of diazepam during and after prolonged administration. AB - Seven volunteers received diazepam for a 3-week period, maximum dose rate 25 mg per day, and were tested on a variety of functions before, at two points during, and at two points after the period. Their performance was compared with that of 8 controls and was inferior on a number of measures. There was no indication either of habituation or of potentiation of the effects as the period continued. Equally, the low performance persisted for some time after administration ceased, although performance was on the whole better than during the experimental period. The particular measures showing deterioration suggested that the effects are similar to those of barbiturates as opposed to those of, for example, chlorpromazine. PMID- 3094050 TI - Binding affinities of four tricyclic antidepressive drugs to muscarinic cholinergic receptors in human parotid gland. AB - The binding kinetics of tritiated quinuclidinyl benzilate (QNB) were studied in membrane preparations from human parotid and rabbit submandibular glands. Inhibition of 3H-QNB was then used to compare the anticholinergic activity of lofepramine, desipramine, imipramine and amitriptyline for muscarinic receptor in the salivary glands. The apparent dissociation constant (KD) for 3H-QNB binding in human parotid and rabbit submandibular gland was 33 and 61 pM and the Bmax value 507 and 169 f mol/mg protein, respectively. The mean values for the inhibition constant (Ki) for lofepramine, desipramine, imipramine and amitriptyline in human parotid gland were 285, 135, 102 and 13 nM, respectively. Very similar values were obtained for the rabbit submandibular gland. The binding affinity of tricyclic antidepressants for muscarinic cholinergic receptor sites in human parotid gland closely paralleled clinical data on the inhibition of salivary flow by these drugs. PMID- 3094051 TI - Effects of nicotine on body weight and food consumption in female rats. AB - Women often report that they smoke cigarettes to avoid weight gains and that they relapse after abstaining from tobacco because of weight gains. Men also report these concerns but to a lesser extent. This gender difference may reflect sociological and cultural pressures about physical appearance, or it may reflect sex differences in the effects of nicotine. The present research was designed to examine the effects of nicotine administration and cessation of nicotine on body weight, food consumption, and water consumption. Alzet miniosmotic pumps were implanted SC to administer saline or three different concentrations of nicotine to female Sprague-Dawley rats for 17 days. This paradigm has been used in previous studies of nicotine and body weight in male rats. Animals were used as subjects to avoid cultural factors and cognitive concerns about body weight. Nicotine administration decreased normal body weight gains and cessation of nicotine was accompanied by significant increases in body weight compared to controls. In contrast to previous studies of male rats, the nicotine-related changes in body weight were accompanied by changes in bland food and water consumption. These findings indicate that females are more sensitive than males to the effects of nicotine on body weight and feeding during and after drug administration. PMID- 3094052 TI - GABA and behavioral inhibition in the neonatal rat pup. AB - The effects of the GABA agonist muscimol and GABA antagonist picrotoxin were examined in 3-4-day-old deprived rat pups under conditions of low (absence of milk) and high (milk presence) activity baselines. A low dose of muscimol was observed to have activating effects under low baseline conditions, whereas higher doses of muscimol were observed to depress milk-induced activity and mouthing. Picrotoxin treatment was observed to increase activation of these neonates under both baseline conditions. Taken together, these results provide evidence for a functional GABAergic inhibition of behavior in the neonate. PMID- 3094053 TI - Acute versus repeated administration of desipramine in rats and mice: relationships between brain concentrations and reduction of immobility in the swimming test. AB - Immobility scores in the swimming test and brain concentrations of desipramine were determined in rats and mice following repeated injection of the antidepressant versus acute administration of either a behaviorally effective or ineffective dose of the drug. Five injections (IP) of desipramine (each injection being performed at the measured T1/2 of the drug in the brain) reduced immobility scores by 30%, whereas this regimen resulted in brain drug concentrations not different from those obtained after a single, behaviorally ineffective dose of desipramine. It is suggested that the enhanced "antidepressant" response such as that frequently observed in animals after repeated injection of imipramine-like drugs does not involve accumulation of the drug in the brain. PMID- 3094054 TI - Effects of acute marijuana smoking in post-menopausal women. AB - Acute effects of marijuana and placebo cigarette smoking on pulse rate and self estimations of mood and level of intoxication were studied in ten post-menopausal women. Six women had no prior experience with marijuana. Four subjects had a total of seven marijuana smoking experiences, none of which occurred during the past year. Statistically significant increases in pulse rate and level of intoxication followed marijuana but not placebo cigarette smoking. Marijuana smoking also induced a significant increase in symptoms of confusion and a decrease in self-report indices of arousal. PMID- 3094055 TI - A method for quantifying state-dependency with chlordiazepoxide in rats. AB - A state-dependency procedure is described in which changes from the chlordiazepoxide state yield a robust and dose-dependent response decrement in rats. The format of data that are obtained with this procedure permits that the response decrement following a state change be defined accurately in individual animals, and that transfer be quantified. Dose-response studies revealed 13 (7.4 22) mg/kg to be the ED50 of chlordiazepoxide at which transfer occurred in animals that had acquired the response with 40 mg/kg chlordiazepoxide; the ED50 acquisition dose of chlordiazepoxide at which transfer to saline failed to occur was 3.7 (2.2-6.4 mg/kg). PMID- 3094056 TI - Bromocriptine induces marked locomotor stimulation in dopamine-depleted mice when D-1 dopamine receptors are stimulated with SKF38393. AB - In mice pretreated with reserpine plus alpha-methyl-p-tyrosine, neither the D-2 selective agonist bromocriptine, nor the D-1 selective agonist SKF38393, produced any measurable increase in locomotion in mice. However, the combination of the two agonists produced a marked and dose-dependent increase in co-ordinated locomotor activity. In mice with their dopamine stores and dopamine synthesis intact, SKF38393 was inactive by itself, but significantly enhanced the stimulant effect produced by bromocriptine. The data suggest that bromocriptine requires concomitant stimulation of D-1 receptors for the full expression of its behavioural stimulant effects. PMID- 3094057 TI - Enhancement of the memory of a previously learned aversive habit following pre test administration of a variety of serotonergic antagonists in mice. AB - The present study examined the effects of pre-test administration of a number of serotonergic receptor antagonists on the retrieval of a previously learned aversive habit in the mouse. All of the receptor antagonists (pirenperone, ketanserin, mianserin, methysergide and metergoline) produced a dose-dependent increase in the latency to complete 5 s of drinking 48 h after training. This suppression of drinking could not be attributed to nonspecific effects of the drugs on behavior (e.g., illness, reduced thirst, or activity), as non contingently trained mice failed to exhibit similar elevations in their test scores. These results are, therefore, further support for an important role for serotonin in the processes underlying learning and memory. PMID- 3094058 TI - Role of monoamine pathways in the control of attention: effects of droperidol and methylphenidate in normal adult humans. AB - Methylphenidate (0.65 mg/kg), droperidol (15 micrograms/kg) or placebo were administered to normal adult males undertaking a dichotic auditory attention task. Performance following placebo, as measured by the ability of subjects to detect nominated target words and discriminate them from phonemically distracting words, was superior when attention was focused on one ear than when divided between the ears. Following droperidol, target detection and discrimination were reduced for both divided and focused attention and in the latter case responses were also slowed. However, these effects were small compared to the striking withdrawn behaviour of the subjects, who reported an unwillingness to attend to external events. Methylphenidate reversed all of these effects when administered following droperidol. Administered alone, methylphenidate had no effect on dichotic measures of attention but had marked effects on spontaneous behaviour, when most subjects reported a substantial increase in both the field and distractibility of attention. These results are interpreted as implicating central dopaminergic pathways in the regulation of attention without precluding a role for other neurotransmitter systems including ascending noradrenaline and serotonin pathways to cerebral cortex. The disparity between these objective and subjective assessments of the effects of the drugs on attention is discussed in terms of the degree of mental effort voluntarily brought to bear by subjects in the selective allocation of their attentional capacity. PMID- 3094059 TI - Role of monoamine pathways in attention and effort: effects of clonidine and methylphenidate in normal adult humans. AB - Methylphenidate (0.65 mg/kg), clonidine (200 micrograms) or placebo were administered to normal adult males undertaking a dichotic monitoring task in which they were required to detect nominated target words and discriminate them from phonemic distractors. Following placebo, performance was better when attention was focused than when divided. Following clonidine, subjects were poorer and slower at discriminating targets during both divided and focused attention and subjectively were withdrawn and reported difficulties with concentration. Methylphenidate had no effect on target discrimination or response time but raised the rate of response and had marked effects on spontaneous behaviour in which an increased attention capacity was generally reported. The effects on attention of the pharmacological agents employed in this study are attributed to their effects on central monoamines. The disparity noted between objective and subjective assessments of attention is discussed in terms of the voluntary allocation of effort. PMID- 3094060 TI - Individual and morphological differences in the behavioural response to apomorphine in rats. AB - The topography of stereotyped behaviour produced by apomorphine in rats was studied by using either a scoring system, based on observation in a wire cage, or by quantification of horizontal and vertical activities, and of the total distances run in an open field, using an automatic recording system. The latter design was combined with a classification of the type of stereotyped behaviour observed during recording. In addition, the reproducibility of the nature of the stereotyped behaviour and its dose-dependence in individual animals was evaluated. In rats observed in a wire cage, apomorphine at lower doses (0.25 or 0.50 mg/kg SC) produced stereotyped sniffing. Increasing the doses led to stereotyped licking and the largest dose (5.00 mg/kg SC) produced predominantly stereotyped gnawing, as was demonstrated graphically. The type of behaviour produced by 2 mg/kg apomorphine in the open field was reproduced well in individuals after a second administration 4 days later. The shift from sniffing to gnawing was observed in most, but not all of the individually classified animals after administration of the largest dose (5 mg/kg). The locomotor part of motility was highest in "sniffing animals" and lower when gnawing occurred. The non-locomotor part of motility was low in "sniffing rats" and increased when licking and gnawing occurred. In some of the animals a characteristic "climbing" behaviour was observed in addition after the larger doses, which did not interfere with sniffing, licking or gnawing. A combination of classification by observation and automatic recording seems the most appropriate way to study the topography of stereotyped behaviour produced by apomorphine. PMID- 3094061 TI - Effect of ceruletide on tardive dyskinesia: a pilot study of quantitative computer analyses on electromyogram and microvibration. AB - Seven patients with bucco-lingual dyskinesia were treated with a single dose of ceruletide 0.8 micrograms/kg IM, a potent analogue of cholecystokinin octapeptide. Time-course effects of the drug were then followed up to 6 weeks after injection in the longest case. To assess changes in severity of dyskinesia objectively, electromyogram and microvibration were recorded. These data were subjected to the Fast Fourier Transform and an averaged power spectrum was computed. The effect of ceruletide on dyskinesia within 2 h after injection differed (three cases: inhibitory, two cases: facilitatory, two cases: no effect). It was notable that a long-lasting inhibitory effect of this peptide was observed in two severe irreversible cases. The present findings might contribute to further understanding of the physiopathophysiological role of cholecystokinin like peptides in the brain and to practical treatment of tardive dyskinesia. PMID- 3094062 TI - Conditional tolerance to haloperidol-induced catalepsy is not caused by striatal dopamine receptor supersensitivity. AB - The purpose of this study was to determine if non-pharmacological stimuli influence behavioural tolerance to haloperidol via striatal postsynaptic dopamine receptors. Rats received daily haloperidol and saline in two different environments for a period of 28 days. After this conditioning period half of the rats received haloperidol in the haloperidol-associated environment, whereas the other half received haloperidol in the saline-associated environment. All rats were tested for catalepsy and at the end of the last catalepsy test, striatal DOPAC, HVA and ACh were determined. Only the rats tested in the haloperidol associated environment were behaviourally tolerant to haloperidol. In contrast, both groups were biochemically tolerant to haloperidol. These results indicate that environmental cue factors govern the development of behavioural tolerance to haloperidol, rather than biochemical factors (striatal DA super-sensitivity). In addition, these factors do not exert their influence on behavioural tolerance via striatal DA receptors. PMID- 3094063 TI - Desamino-D-arg8-vasopressin (DDAVP), unlike ethanol, has no effect on a boring visual vigilance task in humans. AB - It has been suggested that vasopressin (VP) and its analogues such as desamino-D arg8-vasopressin (DDAVP) affect cognitive (including mnemonic) and attentional processes in man. We describe the effects of DDAVP and ethanol (EtOH) on young, healthy human volunteers, using a recently developed visual search task which assesses attention and vigilance. Over a 1-h session, the subject has to detect the occurrence of certain digits in a long list of random characters. A low dose of EtOH (0.33 ml/kg) tended to improve, and a higher dose (1.0 ml/kg) disrupted performance. DDAVP (20 or 60 micrograms/subject) had no effect whatsoever. It is concluded that intranasal administration of the peptide analogue does not markedly affect attention performance in human subjects. PMID- 3094064 TI - Dopamine autoreceptors in the ventral tegmental area show subsensitivity following withdrawal from chronic antidepressant drug treatment. AB - The suppression by apomorphine of food intake and eating time was used to assay the sensitivity of dopamine cell body autoreceptors during the course of treatment with DMI, amitriptyline and mianserin. Brief (2-4 days) DMI treatment enhanced the effects of apomorphine, administered systemically or centrally to DA cell body regions. During chronic DMI treatment (3-7 weeks) some evidence of autoreceptor subsensitivity was observed with systemic apomorphine, but not with central apomorphine. Responses to apomorphine applied systemically were reduced during withdrawal from chronic DMI, and responses to apomorphine applied to the ventral tegmental area were reduced during withdrawal from all three antidepressants. As evidence of DA autoreceptor subsensitivity was only observed reliably during withdrawal, this effect is unlikely to be of clinical importance. PMID- 3094065 TI - The effects of d-amphetamine, alpha-flupenthixol, and mesolimbic dopamine depletion on a test of attentional switching in the rat. AB - A test of attentional switching was devised for the rat in which it obtained sucrose reinforcement by an appropriate nose-poke response that discriminated which of two visual events terminated first, in a specially designed chamber. The effect of mesolimbic dopamine depletion (to 20% of control values) produced by infusions of 6-hydroxydopamine (6-OHDA) into the nucleus accumbens (N. Acc) on stable discrimination was measured alone and in the presence of a range of doses of d-amphetamine (0.4-2.3 mg/kg IP). The 6-OHDA lesion of the N. Acc impaired postoperative performance transiently by reducing choice accuracy and slowing response latency. By post-operative days 12-16, however, performance recovered to control levels and was not differentially affected by a manipulation of task difficulty. d-Amphetamine produced dose-dependent performance impairments, which were antagonised by the 6-OHDA treatment. In a second group of N. Acc lesioned rats, the neuroleptic alpha-flupenthixol (0.1-1.0 mg/kg) led to fewer trials being completed and longer latencies than in the sham-operated control group. The results are discussed in terms of the possible attentional mechanisms underlying the d-amphetamine-induced disruption of performance mediated by the N. Acc and of the implications for psychopathology resulting from possible dysfunction of this region. PMID- 3094066 TI - Conditioned taste aversion and conditioned drinking: two independent and opposing effects of 5-hydroxytryptophan? AB - Four experiments were carried out to examine the effects of 5-HTP in a conditioned taste aversion (CTA) paradigm. Using two-choice tests to measure the CTA, administration of 5-HTP following consumption of a novel flavour caused aversions to saline and saccharin solutions. In single-choice tests 5-HTP reduced consumption of saccharin, sugar cubes and beef-flavoured stock cubes, but only reduced saline consumption if animals had been pretreated with the 5-HTP decarboxylase inhibitor benserazide or the 5-HT receptor antagonist xylamidine, both of which act peripherally. Benserazide did not attenuate the CTA in any experiment. The results are interpreted in terms of two competing behavioural effects of 5-HTP: a centrally-mediated CTA and a peripherally-mediated conditioned drinking response. PMID- 3094067 TI - Withdrawal from chronic nicotine substitutes partially for the interoceptive stimulus produced by pentylenetetrazol (PTZ). AB - Rats were trained on an FR10 schedule of food reinforcement to press one lever after pentylenetetrazol (PTZ), 20 mg/kg, IP, and an alternate lever after saline. After acute nicotine, 0.64 mg/kg, SC, 35% of the rats pressed the PTZ-lever. Diazepam, 5 mg/kg, IP, blocked the stimulus produced by PTZ, and mecamylamine, 5 mg/kg, IP, blocked the stimulus produced by nicotine. Training was then suspended and rats were treated with nicotine, at 8-h intervals, 0.64 mg/kg on the 1st day, and 1.25 mg/kg on subsequent days, for 21 days. To determine whether nicotine withdrawal substitutes for the stimulus produced by PTZ, rats were tested with saline at various times after chronic nicotine injections. Data from this part of the study were replicated in another group given nicotine for 15 days. Saline at 8 h after nicotine (five determinations each group) produced a small but stable degree of PTZ lever selection (35 +/- 4%). At 48 h after termination of nicotine treatment, the percentage of rats selecting the PTZ lever (50%) was greater than that in a control group tested after an equivalent period without training. The PTZ-like stimulus detected after chronic nicotine was not altered by mecamylamine, was additive with PTZ, and was blocked by diazepam. These data suggest that withdrawal from chronic nicotine produces a weak PTZ-like stimulus, which can be antagonized by an anxiolytic drug. PMID- 3094068 TI - Noradrenergic and opioid mediation of tricyclic-induced reversal of escape deficits caused by inescapable shock pretreatment in rats. AB - The present study was undertaken to investigate the possible involvement of a noradrenergic and opioid mediation of the reversal by tricyclic antidepressants of escape deficits produced by inescapable shock pretreatment. Rats were first exposed to 60 inescapable shocks (15 s duration, 0.8 mA, every min +/- 15 s) and 48 h later subjected, to daily shuttle-box sessions (30 trials/day, ITI: 30 s) during 3 consecutive days. Twice-daily IP injection of desipramine or clomipramine (total daily dose: 32 mg/kg) prevented escape deficits. Penbutolol (0.125; 0.25; 0.5 mg/kg), prazosin (1; 2 mg/kg) and naloxone (0.5; 1 mg/kg) given once a day dose-dependently attenuated the beneficial effect of tricyclic antidepressants in reducing the number of escape failures in rats exposed to shock pretreatment. In agreement with data obtained in the forced-swimming model, these findings support the notion that activation of noradrenergic and opioid receptors is an important factor in the mediation of the effects of tricyclic antidepressants in animal models of depression. PMID- 3094069 TI - The effects of clonidine on the partial reinforcement extinction effect (PREE). AB - Clonidine has been reported to exert anti-anxiety effects in animals and man similar to those of benzodiazepines. The present experiment examined the effects of clonidine administration on the partial reinforcement extinction effect (PREE) which is known to be sensitive to benzodiazepine action. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasi-random 50% schedule. All animals were then tested in extinction. Clonidine 50 micrograms/kg was administered in a 2 X 2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction exhibited by PRF animals as compared to CRF animals, was obtained in animals that received saline in acquisition, independently of drug treatment in extinction, as well as in animals that received clonidine in both acquisition and extinction, but not in animals that received clonidine in acquisition alone. The administration of clonidine in extinction alone increased resistance to extinction in both the CRF and PRF animals. The increase in resistance to extinction, typically obtained with benzodiazepine treatment, indicates that clonidine exerts anxiolytic effects, supporting the involvement of the noradrenergic system in anxiety. However, clonidine did not fully reproduce the effects of benzodiazepines on the PREE, suggesting that the two classes of drugs may act via different noradrenergic mechanisms. PMID- 3094070 TI - Back blows and chest thrusts for choking victims? Dr. Heimlich answers. PMID- 3094071 TI - Treatment for choking infants: some controversy lingers. PMID- 3094072 TI - Smoking study formula may yield big errors. PMID- 3094073 TI - Identifying mesotheliomas on death certificates. PMID- 3094074 TI - Acquired immunodeficiency syndrome: current and future trends. PMID- 3094075 TI - 10 years after NHANES I: report of initial followup, 1982-84. AB - The NHANES I Epidemiologic Followup Study (NHEFS) was jointly initiated by the National Center for Health Statistics and the National Institute on Aging in collaboration with other National Institutes of Health and Public Health Service agencies. The goal of NHEFS is to examine the relationship of baseline clinical, nutritional, and behavioral factors assessed in the first National Health and Nutrition Examination Survey (NHANES I-1971-75) to subsequent morbidity and mortality. Data collection for the initial phase of followup took place between 1982 and 1984 and included tracing of all NHANES I participants, determining their vital status, conducting in-depth interviews with surviving participants or with proxies for those who were deceased or incapacitated, conducting selected physical measurements, obtaining facility records for stays in hospitals or nursing homes that occurred during the period of followup, and obtaining death certificates for decedents. Ninety-three percent of the original cohort was successfully traced. Interviews were conducted for 93 percent of traced, surviving participants and 84 percent of traced, surviving participants and 84 percent of traced, deceased subjects. Physical measurements were obtained for approximately 95 percent of surviving, interviewed subjects. Death certificates are available for more than 95 percent of the decedents, and 18,136 facility records were received for 6,477 subjects. PMID- 3094076 TI - 10 years after NHANES I: mortality experience at initial followup, 1982-84. AB - The NHANES I Epidemiologic Followup Study (NHEFS) was initiated jointly by the National Center for Health Statistics and the National Institute on Aging in collaboration with other National Institutes of Health and Public Health Service agencies. The goal of NHEFS is to examine the relationship of baseline clinical, nutritional, and behavioral factors assessed in the first National Health and Nutrition Examination Survey (NHANES I-1971-75) to subsequent morbidity and mortality. Tracing for the initial followup began in 1981 and ended in 1984. This article compares the mortality experience of the NHEFS cohort with survival probabilities and cause-of-death distributions derived from U.S. vital statistics data. The analysis was done for 28 age-race-sex specific subgroups. The survival of each group of the NHEFS cohort corresponds quite closely to that expected on the basis of the U.S. life table survival probabilities. Mortality differentials by age, race, and sex are also quite similar between NHEFS and U.S. vital statistics. In addition, the cause-of-death distributions among NHEFS participants are quite similar to those expected based on national vital statistics. Thus, there do not seem to be any serious biases in the mortality data. The NHEFS, therefore, provides a unique resource for assessing the effects of baseline sociodemographic, health, and nutritional factors on future mortality in a large, heterogeneous sample that is representative of the nation's population. PMID- 3094077 TI - Management of tuberculosis in urban homeless indigents. AB - Tuberculosis patients who are homeless, indigent, and alcoholic infrequently complete a course of chemotherapy, risking treatment failure, recurrence, and continued spread of infection in the community. Obstacles to successful treatment include an erratic schedule, mistrust of authority, and uncooperative or aggressive behavior. Successful management of this problem requires the use of proven case holding techniques, a correct choice of drug regimen, and a prompt and appropriate response to the patient who is lost or refuses treatment. Nine- and six-month drug regimens with proven success are now available; however, the direct observation of medication-taking should be maximized. Patient default may be further minimized by encouraging prompt notification of the health department. Occasionally, the threat or use of existing public health laws on confinement for purposes of treatment are required for noncompliant patients. PMID- 3094078 TI - The Los Angeles solution. PMID- 3094079 TI - Tuberculosis screening in Boston's homeless shelters. AB - From February 1984, through March 1985, a total of 26 cases of tuberculosis (TB) were verified in homeless persons in Boston. Fifteen cases were resistant to isoniazid (INH) and streptomycin (SM) and were most likely the result of a common source exposure to one or possibly two highly infectious persons. Five cases without multiple drug resistant organisms occurred in persons with previous positive tuberculin tests who had not received adequate therapy for prophylaxis of infection or treatment of disease. The remaining cases were in persons with a previous negative skin test or no history of ever receiving a skin test. A screening program using chest roentgenograms (CXR), skin tests, and sputum smears led to the identification of several cases. CXR, the most readily accepted test, was the mechanism by which all cases detected through screening were identified. Detection and therapy of TB in the homeless, a group at particular risk for disease, required intensive intervention and outreach efforts. PMID- 3094080 TI - Role of nurses in meeting needs of the homeless: summary of a workshop for providers, researchers, and educators. PMID- 3094081 TI - Federal health services grants, 1985. AB - Federal health services grants amounted to about $1.8 billion in fiscal year 1985. The total amount was about $100 million less, about 6 percent, than in 1980. Reductions in the health planning program accounted for most of the decline in absolute dollars. The four formula grants to State agencies amounted to about $1.0 billion in 1985, about 60 percent of the total. The largest formula grants were for maternal and child health services and for alcohol, drug abuse, and mental health services. Project grants to selected State and local agencies amounted to about $.8 billion. There was 12 such grants in 1985 (compared with 34 in 1980). The largest, for community health services, equaled almost half the total. In real, inflation-adjusted dollars, the decline in Federal funds for these programs exceeded a third during the 5-year period. The overall dollar total in real terms in 1985 approximated the 1970 level. The ratio of formula grants to project grants in 1985 was similar to that in 1965. Studies of the impact of changes in Federal grants have found that while the development of health programs has been seriously constrained in most cases, their nature has not been substantially altered. In some cases broader program approaches and allocations have been favored. Established modes of operations and administration have generally been strengthened. Some efficiencies but few savings in administration have been identified. Replacement of reduced Federal funding by the States has been modest but has increased over time, especially for direct service activities. These changes reflect the important influence of professionalism in the health fields and the varying strengths of political interest and influence among program supporters. The long-term impact on program innovation is not yet clear. PMID- 3094082 TI - Effects of mandating seatbelt use: a series of surveys on compliance in Michigan. AB - Although proper use of automobile seatbelts reduces risk of serious injury or death in traffic crashes by 30 to 50 percent, seatbelt use remains low. Recently, several States have passed laws requiring the use of seatbelts. Michigan implemented such a law July 1, 1985. Direct-observation surveys of a probability sample of motorists throughout the State were conducted before the law was passed, after passage but before implementation, immediately after the law took effect, and 5 months after implementation. The results showed a significant increase in the use of restraints from 19.8 percent before the law was passed to 58.4 percent immediately after it took effect. A restraint use survey conducted in December 1985, 5 months after implementation, measured the use of restraints at 43.0 percent. Despite that decline, belt use was 117 percent higher than the 19.8 percent measured before passage of the law mandating the use of seatbelts. PMID- 3094083 TI - Overview of research on women in medicine--issues for public policymakers. AB - The recent expansion of the nation's supply of physicians has brought with it dramatic increases in the number of women entering medical school and practice. This paper provides an overview of the literature on women in medicine and synthesizes major findings on the differences between male and female physicians in terms of specialty choice, productivity, income, geographic location of practice, practice settings and types of patients, leadership within the profession, and other characteristics. Between 1981 and the year 2000, the total supply of physicians in practice is expected to increase by 27 percent; the number of women in practice is expected to increase by 153 percent. By the year 2000, one physician in five will be a woman. The fairly limited research on gender-related differences indicate that women tend to cluster in a few specialties (pediatrics, psychiatry, pathology, preventive medicine, physical medicine and rehabilitation, and anesthesiology), many of which are specialties expected to have fewer physicians than needed nationally by 1990. Women have also been shown to have lower productivity and lower income than male physicians, to choose urban locations more frequently, to prefer salaried and institutional settings more often, to serve different types of patients, and to belong to medical organizations less frequently. From the standpoint of public policy, the differences between the characteristics of male and female physicians have mixed implications. For example, the choice of specialty and lower productivity of women could lessen the negative impact of future physician surpluses. On the other hand, a preference for urban practice could exacerbate geographic maldistribution problems. More research will be required to define and predict the long-term effect of significant increases in the number of female physicians in the United States. PMID- 3094084 TI - The cognitive profile of those who intend to exercise but do not. AB - The purpose of this study was to identify the cognitive profile of people who intend to exercise but fail to carry out this intention. A theoretical framework was adopted to study the attitudinal beliefs of these persons about exercise, their evaluation of the associated consequences, and their normative beliefs and motivation to comply with these norms. Subjects were classified according to the congruence between stated intention and self-reported exercise behavior 2 months later in this way: positive intention and congruent behavior (CONG+, N = 74). positive intention and incongruent behavior (INCONG-, N = 45). negative intention and congruent behavior (CONG-, N = 42). negative intention and incongruent behavior (N = 2, not analyzed). MANOVA analysis indicated little difference between the cognitive profiles of inactive and active positive intenders. Relative to the CONG+ group, the INCONG- group perceived that regular exercise would be "tiring" (P less than 0.001) and "time consuming" (P less than 0.001); they also placed less value on the consequence of "being healthy" (P less than 0.05). Both groups differed from the CONG- group. As would be expected, those with positive intentions to exercise identified more advantages to being physically active. It appears that sedentary positive intenders perceived the exercise behavior as physically demanding and had difficulty in reconciling the time demands of an exercise program with their weekly schedules. This observation suggests that these two beliefs should be considered for the promotion of physical activity as well as the investigation of influential social and environmental variables. PMID- 3094085 TI - Campers' diarrhea outbreak traced to water-sewage link. AB - From June through September 1979, diarrheal illness occurred in an estimated 1,850 persons who had camped at a private campground in Arizona. Illness occurred more frequently among campers at that campground than among those in the adjacent State park (P less than 0.0001). The same well served both the private and the State campgrounds as the source of drinking water, but that water was distributed to the two campgrounds through separate lines. Illness was significantly associated with drinking water at the campsite (P less than 0.0001), drinking larger quantities of campsite water (P less than 0.001), and camping on the southwest side of the campground (P less than 0.001). Samples of the water collected from the system during January through June contained no coliform bacteria. However, all those samples had been collected from the State park only. Of the 11 water samples submitted for bacteriological analyses during the summer, 3 had high levels of bacteria. Excavation of the water system uncovered a direct cross connection between the potable water system and a sewage-effluent irrigation system. This outbreak calls attention to the importance of designing, maintaining, and monitoring potable water systems properly, especially those proximate to wastewater re-use systems. PMID- 3094086 TI - The National Reporting Program for Mental Health Statistics: history and findings. AB - The National Reporting Program for Mental Health Statistics had its origins in the decennial U.S. census, with enumeration of the "insane and idiotic" in 1840. A series of special censuses of the insane and feebleminded in public and private hospitals and other institutions began in 1904, and annual censuses of patients in mental institutions were conducted from 1926 to 1946. The National Institute of Mental Health of the Public Health Service took over responsibility for the annual census of patients in mental institutions in 1947. Coverage and content remained the same until the mid-1960s, when only State and county mental hospitals were included in the census. Because the annual census could not provide the data needed, separate programs were begun for inpatient and outpatient service. These were integrated into the National Reporting Program in 1966. Trend data for the last 40 years describe how the specialty mental health sector has developed. Non-Federal general hospitals with separate psychiatric services increased dramatically, from 81 in 1940 to 1,531 in 1982, as did community mental health centers, from 125 in 1965 to 691 in 1980. There was generally less emphasis on inpatient care and more on outpatient care. Full-time equivalent staff in specialty mental health facilities increased from about 325,000 in 1970 to about 432,000 in 1982. Expenditures by facilities also increased dramatically. PMID- 3094087 TI - Issues in survey data on medical practice: some empirical comparisons. AB - In recent years, researchers and policymakers have used data from large-scale surveys of physicians to address important issues. A review of several of these surveys explores potential problems in this method of gathering data on physicians' services. To obtain a better grasp of the limitations such problems may pose, we examine several recent surveys, comparing response rates and survey findings, and in one survey the reliability of individual items. Response rates appear highly sensitive to differences in the approaches made to respondents and their perceptions of the goals of individual investigations. Reliability of survey items seems to depend on the specificity of information requested. Variation in the findings from different surveys may occur for many reasons, but is most likely to be found in response to items whose presentation differs in each survey's research instrument. Data from these surveys appear clearly useful for some important purposes. The large-scale medical practice survey seems particularly valuable in generating an understanding of differences among specialties in resources used in the delivery of care. Nevertheless, researchers and policymakers must understand the steps necessary to obtain reliable results and possible limitations in the accuracy of findings to make the best use of survey methodology as applied to medical practice. PMID- 3094088 TI - Cancer mortality, ethnicity, and socioeconomic status: two New York City groups. AB - Cancer mortality rates for 1979-81 among Puerto Ricans and non-Hispanic whites in New York City are analyzed for cancer in six sites. They include cancers of the lung, esophagus, breast, stomach, colon, ovary, and all cancers. New York City health areas were divided into four quartiles representing four levels of income. In general, Puerto Ricans in New York City have lower mortality rates from cancer than non-Hispanic white residents of the city. In comparing cancer mortality by quartile, Puerto Rican males show little variation. Puerto Rican females show their highest mortality rates from breast cancer in the wealthiest quartile, and non-Hispanic white women show highest mortality rates from breast cancer in the poorest quartile. Non-Hispanic white males show mortality rates from lung cancer in the poorest quartile that are distinctly higher than in the more affluent ones. For all groups, with the exception of Puerto Rican males, mortality rates from all cancers increased progressively with decreasing income. Factors influencing differential mortality rates by quartile appear to include tobacco use, alcohol consumption, occupational hazards, fertility, and differential use of health facilities. PMID- 3094089 TI - Schistosomiasis and inflammatory polyarthritis: a clinical, radiological and laboratory study of 96 patients infected by S. mansoni with particular reference to the diarthrodial joint. AB - Patients with active Schistosoma mansoni infection attending a medical clinic in an endemic area, 100 miles from Cairo, were asked to participate in this study. Ninety-six patients are reported, 72 of whom presented with musculoskeletal complaints. Nine of these presented with an enthesitis alone; 16 had an inflammatory peripheral polyarthritis alone; the remaining 47 were suffering from the combination of both an arthritis and an enthesitis. Alpha-1-acid glycoprotein was significantly lowered in those patients with musculoskeletal manifestations. PMID- 3094090 TI - Androgenic status and sexual function in males with rheumatoid arthritis and ankylosing spondylitis. AB - The pituitary-testicular axis was investigated in 31 males with rheumatoid arthritis (age range 19-60 years, median 55 years) and 33 males with ankylosing spondylitis (age range 22-55 years, median 37 years) and compared with a control group of 95 normal male volunteers. Using analysis of covariance, patients with rheumatoid arthritis showed significantly lower serum testosterone (p less than 0.05) and derived free testosterone (p less than 0.01) concentrations and significantly higher serum LH and FSH concentrations (p less than 0.05) compared with controls. All patients had normal serum prolactin and cortisol concentrations. Serum testosterone correlated with ESR, haemoglobin concentrations and rheumatoid factor titres (r = -0.448, p less than 0.02; r = 0.440, p less than 0.02; r = -0.360, p less than 0.05 respectively) in the rheumatoid patients. Although there was a significant negative correlation between ESR and haemoglobin concentrations (p less than 0.005) in the patients with ankylosing spondylitis, neither variable correlated with serum testosterone concentrations. There was no association between testicular dysfunction and the presence of extra-articular features of rheumatoid arthritis. Ten patients (33 per cent) with rheumatoid arthritis and four (13 per cent) with ankylosing spondylitis admitted to periods of impotence while 15 (50 per cent) of the former and 12 (39 per cent) of the latter had periods of decreased libido. There was no evidence for increased rates of infertility in either group. PMID- 3094091 TI - [Vascular changes in sporadic ergotism. Epidemiology, pathogenesis, clinical picture and diagnosis with particular consideration of angiographic documentation]. AB - Whereas the epidemic form of ergotism has been rare in the 20th century, the sporadic form has a wide distribution as a consequence of therapy with ergot derivative drugs. Favourable prognosis of the condition, with complete recovery from the ischemic peripheral circulatory disorders can be obtained by early diagnosis. Precise evaluation of the history, with recognition of treatment of migraine headache or postpartum hemorrhage with ergot alkaloids, can be determinative in diagnosis. The specific pattern of the angiographic findings, as we saw it in 6 cases within the last 4 years, decisively confirms the diagnosis. We could demonstrate thread-, thorn- and hour glass-like narrowing of the vessels, due to spasm. Total occlusion with the development of collaterals may occur, but we saw no thrombus formation. The stenotic arterial segments had smooth margins. The distribution of the involved arteries was more focal than generalized and more peripheral than central. In two cases spasm could be abolished immediately by a pharmaceutical (i.a. injection of tolazoline) or by anesthetic procedures (halothane). The phenomenologic data, together with the complete reversal of the circulatory ischemic disorders after therapy (particularly the absolute ban of ergots) in most cases, is so specific that other diseases of ischemic nature (emboli, arteriosclerosis, Buerger's disease, fibromuscular hyperplasia) can be excluded. PMID- 3094093 TI - Synthesis and vascular actions of an arachidonic acid ethylene-diamino-triethyl ester (AA-EDTA) derivative. AB - An ethylene-diamino-triethyl-ester derivative of arachidonic acid (AA-EDTA) was newly synthesized and tested for its coronary vasoactivity in isolated perfused cat coronary arteries. This arachidonic acid analog exerted a coronary vasodilator effect and significantly antagonized the coronary vasoconstrictor effect of LTD4. The constrictor response to the thromboxane analog carbocyclic thromboxane A2 was unaffected by AA-EDTA. These properties of AA-EDTA may be useful in counteracting the vasoconstrictor influence of leukotrienes in situations such as coronary artery vasospasm. PMID- 3094092 TI - Effect of hypoxia on prostacyclin production in cultured pulmonary artery endothelium. AB - Exposure of cultured bovine pulmonary artery endothelial cells to varying levels of hypoxia (10% or 0% O2) for 4 hours resulted in a significant dose-dependent inhibition in endothelial prostacyclin synthesis (51% and 98%, at the 10% and 0% O2 levels respectively, p less than 0.05, compared to 21% O2 exposure values). Release of 3H-arachidonic acid from cellular pools was not altered by hypoxia. Some of the cells were incubated with arachidonic acid (20 microM for 5 min) or PGH2 (4 microM for 2 min) immediately after exposure. Endothelium exposed to 0% O2, but not to 10% O2, produced significantly less prostacyclin after addition of either arachidonic acid (25 +/- 5% of 21% O2 exposure values, n = 6, p less than 0.01) or PGH2 (31 +/- 3% of 21% O2 exposure values, n = 6, p less than 0.05). These results suggest that hypoxia inhibits cyclooxygenase at the 10% O2 level and both cyclooxygenase and prostacyclin synthetase enzymes at the 0% O2 exposure levels. Exposure of aortic endothelial cells resulted in a 44% inhibition of prostacyclin at the 0% exposure level. No significant alteration in prostacyclin production was found in pulmonary vascular smooth muscle cells exposed to hypoxia. These data suggest that the increased prostacyclin production reported in lungs exposed to hypoxia is not due to a direct effect of hypoxia on the main prostacyclin producing cells of the pulmonary circulation. PMID- 3094094 TI - The effects of mefenamic acid on postprandial intestinal carbohydrate metabolism. AB - The effects of mefenamic acid on the food-induced changes in intestinal carbohydrate metabolism were determined in an attempt to elucidate the mechanism(s) by which inhibition of prostaglandin synthesis enhances the postprandial increases in intestinal blood flow and oxygen consumption. The data show that when the luminal perfusate was changed from saline to a nutrient/bile solution, there was an increase in carbohydrate utilization, which was offset by absorption of glucose from the lumen. Intravenous administration of mefenamic acid significantly increased both carbohydrate absorption and metabolism when food was placed in the lumen. Changes in carbohydrate absorption and metabolism have been shown to play and important role in determining the magnitude of glucose induced changes in intestinal blood flow and oxygen consumption. Therefore, it is possible that the ability of mefenamic acid to enhance significantly the food-induced increases in blood flow and oxygen consumption may be due in part to its effects on intestinal carbohydrate absorption and utilization. PMID- 3094095 TI - Polycations as prostaglandin synthesis inducers. II. Structure-activity relationships. AB - Moderately high molecular weight polycations stimulate arachidonic acid release with concomitant synthesis and release of prostaglandins in cultured 3T3 mouse fibroblasts. We have examined a series of synthetic polycations for prostaglandin synthesis-inducing activity as an approach to defining the structural features required for activity. Extensive (greater than 80%) acetylation of poly(vinylamine) was tolerated without loss of activity, indicating that a uniform high density of charges is not required. However, complete acetylation of poly(vinylamine) abolished activity, indicating that some positive charges are required for activity. full activity was observed for charge densities in the range of one per two to one per six atoms of polymer backbone. Branched and linear polycations activated equally well. Location of the charge with respect to the polymer backbone did not affect activity in polymers bearing charges located up to seven atoms away from the backbone. Polycations lacking primary or secondary amino groups exhibited full activity, indicating that Schiff base formation is not required for activity. These results are consistent with a model in which activation involves electrostatic interactions with discrete anionic sites on the target cell. PMID- 3094096 TI - Stimulation of cyclooxygenase by activated human neutrophils is enhanced by uric acid. AB - Activated human neutrophils supernatant enhances prostanoids production by bull seminal cyclooxygenase (455% of control). Superoxide anion and hydrogen peroxide are not involved in this stimulation, in these experimental conditions. Myeloperoxidase (by its hemic nature) and HPETEs (by their -OOH function) could trigger cyclooxygenase. In the presence of uric acid (10(-3) M), a potent hydroxyl radical scavenger, the cyclooxygenase stimulation by supernatant is increased until 709% of the control. PMID- 3094097 TI - Opposite effects of adrenalectomy on eicosanoid release in rat peritoneal macrophages and spleen. AB - The effect of adrenalectomy on the formation of cyclo-oxygenase and lipoxygenase products by activated peritoneal rat macrophages was determined and compared with that of the spleen. After isolation, the cells and tissues were incubated with [1 14C] arachidonic acid and the Ca-ionophore A23187 and the metabolites isolated by HPLC chromatography. The main components formed in the macrophages of the controls are 6-keto-PGF1 alpha, TxB2 and 12-HETE. One peak represents 5, 12 di HETE. Smaller amounts of PGF2 alpha, PGE2, PGD2, LTB4 and 15-HETE are also present. After adrenalectomy, a considerable increase occurs in the amounts of LTB4, 15-HETE and 12-HETE. The increase in the PG is smaller. The compounds formed from endogenous arachidonic acid are also determined. In the cells of the controls, the formation of LTB4 is considerably increased after adrenalectomy. In the spleen, PGD2 and 12-HETE are decreased after adrenalectomy. The effect of the macrophages is most probably related to a diminished amount or inactivation of lipocortin, a glucocorticosteroid induced peptide with PlA2 inhibitory activity in adrenalectomized animals. In the decrease in formation in the spleen, the absence of the permissive effect of glucocorticosteroids on the hormone-induced lipolysis may play a role. PMID- 3094098 TI - Covalent binding of eicosanoids to platelet proteins. AB - Following an incubation of washed human platelets with 14C-arachidonic acid, a small fraction of the radioactivity became tightly bound to the protein pellet. Three criteria suggested that it was actually a covalent binding: it was not removed by exhaustive extractions with solvents of various polarities, it was not dialysable against SDS-buffer and it corresponded to the labeling of several protein bands after SDS-polyacrylamide gel electrophoresis. The use of several pharmacological agents (indomethacin, eicosatetraynoic acid, dazoxiben, diamide) has allowed us to divide this binding into three components: the first one, independent from both cyclooxygenase and lipoxygenase, the second one dependent on cyclooxygenase products and finally the third one, dependent on lipoxygenase products. PMID- 3094099 TI - Regulation of prostaglandin biosynthesis by human ovarian follicular fluid: a mechanism for ovulation? AB - We have studied the effect of human ovarian follicular fluid on PG production by bovine seminal vesicles in vitro and found that hFF1 contains a factor of high molecular weight (Mr greater than 30,000) which inhibits PG synthase in a dose dependent manner. Exposure of this substance to protease activity produced a factor of lower molecular weight (Mr less than 1000) which stimulated PG synthase activity. If this is true of ovarian follicles in vivo, it is possible that increased follicular protease activity stimulates PG synthesis at the time of ovulation. PMID- 3094100 TI - Cyclo-oxygenase blockers influence the effects of 15-lipoxygenase metabolites of arachidonic acid in isolated canine blood vessels. AB - In canine saphenous veins both the 15-hydroxy- and 15-hydroperoxy derivatives of arachidonic acid, 15HETE and 15HPETE, caused endothelium-independent contractions which were not affected by a variety of classical receptor antagonists. These contractions were markedly augmented by cyclooxygenase blockers; nifedipine, which did not influence the contractions induced by lipoxygenase products, inhibited the potentiating effect of indomethacin. In the veins, 15HETE and 15HPETE also induced spontaneous rhythmic contractions which persisted after several washings but could be blocked by inhibitors of cyclooxygenase. In coronary, splenic, renal and femoral arteries, 15HETE and 15HPETE caused contractions which were also augmented by indomethacin and were dependent on the influx of extracellular calcium as they were inhibited by verapamil. Both 15 lipoxygenase metabolites evoked relaxations during contractions induced by prostaglandin F2 alpha or the thromboxane-mimetic U46619. These relaxations were not endothelium-dependent but were inhibited by indomethacin; they did not occur when the initial contractions were caused by K+, norepinephrine or 5-HT. Our results illustrate multiple vascular actions of 15HETE and 15HPETE in dog blood vessels. PMID- 3094101 TI - Frequency of nasoenteral tube displacement and associated risk factors. AB - A pilot study was conducted to describe the frequency with which spontaneous tube displacement occurred in 105 tube-fed patients followed on a prospective basis. In addition, risk factors thought to be associated with tube displacement were studied. Since only about one-third of the tubes were monitored by followup radiographs, the actual occurrence of tube displacement is unknown. On those days when tube position was documented, a comparison of risk factors for spontaneous tube displacement was made with chi-square statistics. Two risk factors, coughing and decreased level of consciousness, were found to occur with significantly greater frequency in patients with displaced weighted nasogastric tubes, while coughing, tracheal suctioning, and upper airway intubation were significant in the dislodgement of unweighted nasointestinal tubes. None of the risk factors were significant in patients with weighted nasointestinal tubes. PMID- 3094102 TI - In vitro release of growth hormone-releasing factor from rat hypothalamus: effect of insulin-like growth factor-1. AB - The release of growth hormone-releasing factor (GHRF) from rat hypothalamus was investigated in vitro. After 60 min preincubation the released GHRF from sliced rat hypothalamic fragments during 60 min incubation was detected by a highly specific and sensitive radioimmunoassay for rat GHRF. The release of GHRF was Ca2+-dependent and enhanced by high concentration of K+. Insulin-like growth factor-1 (IGF-1) significantly decreased GHRF release to 65% and 84% of the control at concentrations of 10(-8) M and 10(-7) M, respectively. These results suggest that this in vitro system is useful for the investigation of the mechanism of GHRF release from the hypothalamus and that IGF-1 is probably involved in the feedback inhibition of growth hormone secretion by attenuating GHRF release from the hypothalamus besides countering the effect of GHRF on the pituitary. PMID- 3094103 TI - [The impact of world recession on the children]. PMID- 3094104 TI - [Ambulatory treatment of protein-calorie malnutrition of infants. Infant nutrition center]. PMID- 3094106 TI - [Prevalence of protein-energy malnutrition in gastroenterologic patients]. PMID- 3094105 TI - [Changes in CO2 end-expiratory fraction after ischemia release in orthopedic surgery]. PMID- 3094107 TI - [Zinc sulfate in various models of acute experimental ulcer]. PMID- 3094108 TI - [Occupational factors in rheumatic diseases as a principle of rehabilitation- analysis of patients of the pension insurance administration for workers in Austria]. AB - The study evaluates unselected "blue-collar" patients (n = 642) included under the social insurance law guidelines of rehabilitation. Rehabilitation measures had become necessary in these patients because of existing or impending invalidity in diseases of rheumatic origin. In 421 patients (= 66%), a connection with the place of work appeared possible. This entailed adaptation or change of the place of work in 297 patients (= 71%), the result of these measures after a period of two to three years being described. General aspects of occupational rehabilitation measures are discussed. PMID- 3094109 TI - Patterns of infection with Buxtonella sulcata in British cattle. AB - Buxtonella sulcata cysts were recovered from the faeces of adult cows on nine commercial dairy farms. Overall, 44.6 per cent of 496 animals sampled exhibited patent infections during the course of the study. Seasonal fluctuations in the prevalence of infection and cyst excretion rate were related to changes in diet and opportunities for transmission. An increase in prevalence of infection with lactation number was also demonstrated. PMID- 3094110 TI - Ventilatory response of the conscious or anesthetized cat to oxygen breathing. AB - In conscious intact cats, oxygen breathing for up to 1 h does not modify ventilation, and the ventilatory response to CO2 in hyperoxia is not consistently decreased. However, oxygen breathing induces sustained hyperventilation in conscious cats after carotid body denervation. In anesthetized cats, oxygen breathing provokes a hypoventilation which is transient under light anesthesia but more sustained under deeper levels of anesthesia. At all levels of anesthesia, the ventilatory response to CO2 is decreased in hyperoxia as compared with normoxia. These results suggest that: the effects of hyperoxia include a central stimulating component, seen only in conscious animals, which offsets the decreased ventilatory drive from peripheral chemoreceptors; this central component is sensitive to anesthesia, thus allowing an explanation for the permanent decrease in ventilation and decrease in ventilatory response to CO2 observed when oxygen is given during deep anesthesia; and anesthesia may help to purposefully unmask factors involved in the control of breathing, but it markedly alters the normal functioning of the respiratory network. PMID- 3094111 TI - [Chronic intermittent peritoneal dialysis: cycles with or without dwell-time?]. PMID- 3094112 TI - [Effects of industrial poisons on human chromosomes under conditions of occupational exposure]. PMID- 3094113 TI - [Possibilities and limits for preventing infections in persons with a cellular immunity deficit]. PMID- 3094115 TI - [Serum zinc levels of the eutrophic and the malnourished infant]. PMID- 3094114 TI - [The menopause and its implications]. PMID- 3094116 TI - [Epidemiological data on hepatitis virus circulation in the Tirgu-Mures area]. PMID- 3094117 TI - [Assessment of the mutagenic potential of industrial toxins via the micronucleus test]. PMID- 3094118 TI - [Role of interventional radiology in the treatment of obstructive jaundice]. PMID- 3094119 TI - [Radiation therapy combined with hyperthermia in advanced cancer]. AB - Radiation therapy combined with radiofrequency (RF) hyperthermia was performed on 5 advanced cancer patients. Included were one each with urinary bladder cancer, hepatoma with left axillary node metastasis, breast cancer, tongue cancer with left cervical metastasis, and mandibular cancer. All had large tumours, which were judged to be uncontrollable by radiotherapy alone. They were treated with irradiation (Linac: 10 MV X-ray 1.8-2.0 Gy/day, 5 days/week), followed within an hour by RF hyperthermia once or twice a week. Partial response was obtained in the urinary bladder cancer patient. Surface overheating around the margin of electrodes occurred in all but no severe complications were observed. PMID- 3094120 TI - Discrimination and other statistical intervals for the interpretation of in vivo patient monitoring data. AB - A calibration line is used to define the relationship between a new clinical technique and a standard in vitro laboratory methodology. Discrimination intervals quantify the reliability of inverse estimates obtained from the calibration line. Applied to transcutaneous PCO2 monitoring, a new in vivo measurement, discrimination intervals for inverse estimates of arterial PCO2 range in size from 10 to 50 torr (1.33-6.67 kPa), or more, depending on the values of statistical parameters selected. Discrimination interval analysis shows that the inverse estimates are more reliable near the means. Also, it indicates that the primary value of transcutaneous PCO2 monitoring lies not in providing accurate inverse estimates of arterial PCO2, but instead, in monitoring short term clinical trends. PMID- 3094121 TI - [Childhood cardiomyopathies]. PMID- 3094122 TI - [Acquired immunodeficiency syndrome in children]. PMID- 3094123 TI - [Glycosylation of hemoglobin and proteins in children with diabetes mellitus. Consequences and clinical applications]. PMID- 3094124 TI - [Correlative clinico-experimental study of immunoglobulins G and albumin in the blood of children with subacute sclerosing panencephalitis, acute lymphoblastic leukemia and viral meningitis]. PMID- 3094125 TI - [Sudden death syndrome in small children. Data from the literature and personal experience]. PMID- 3094126 TI - [Epidemiological aspects of arterial hypertension in children]. PMID- 3094127 TI - [Iatrogenic osteitis of the calcaneus in the newborn infant]. PMID- 3094128 TI - [A case of Lyell's syndrome (acute epidermal necrolysis)]. PMID- 3094129 TI - [The intrauterine system with progesterone and synthetic progestational hormones]. AB - Release of progesterone in the endouterine system modifies the cervical mucus and blocks proliferation of the endometrium. The mode of action is therefore hemostatic, antalgic and contraceptive. Results are excellent in these three, often combined indications. PMID- 3094130 TI - [Value of cyclofenil in the inhibition of lactation. Efficacy compared to bromocriptine]. AB - The inhibitory effects of cyclofenil and bromocriptine on lactation as well as FSH, prolactin and estradiol levels have been compared in control and treated females. The clinical activity of cyclofenil was lower than that of bromocriptine but was virtually free of side-effects. Cyclofenil and bromocriptine only presented similar hormonal effects at the 20th day ; this suggests that the mechanism of action of cyclofenil is more linked to secondary increases in estrogen levels than to a primary effect. Cyclofenil is of particular value in cases of vascular hypersensitivity yo ergot derivatives and for toxemic patients treated with beta-blockers. PMID- 3094131 TI - [Effect of gamma rays on blood forms of Trypanosoma cruzi. Experimental study in mice]. PMID- 3094132 TI - Dynamics of transmission of Trypanosoma cruzi in a rural area of Argentina. I- The dog reservoir: an epidemiological profile. PMID- 3094133 TI - Hypoxanthine and xanthine in stored SAGM-blood. AB - The concentration of xanthine and hypoxanthine was measured in 8 portions of SAGM red cell concentrates during 4 wk storage. The concentration of xanthine increased from 4.2 to 35.1 mumol/l and the concentration of hypoxanthine increased from 16.8 to 165.2 mumol/l (mean values). Previous studies have demonstrated several important effects of purine bases--among these a reduced cytotoxicity of purine antimetabolites. It is concluded that further studies are necessary to investigate the clinical role of purines in stored blood products. PMID- 3094134 TI - Reticuloendothelial system Fc-receptor function in patients with immune thrombocytopenia after treatment with high dose intravenous immunoglobulin. AB - Reticuloendothelial system Fc-receptor (FcR) function was measured in 4 healthy controls and 9 patients with immune thrombocytopenia before and after therapy with high dose i.v. gammaglobulin (HDIg). Idiopathic thrombocytopenic purpura (ITP) was diagnosed in 5 patients. 2 patients with hemophilia A, 1 with acute tuberculosis and 1 with psoriasis vulgaris had thrombocytopenia that clinically resembled ITP. 4 out of 9 patients received prednisone prior to or during the study. FcR blockade was observed only in patients with ITP not receiving prednisone. In all other patients, HDIg did not induce a measurable FcR blockade. However, all except 1 patient (with acute tuberculosis) showed a marked rise in platelet counts for 2 to 12 wk. This is consistent with therapeutic efficacy of HDIg in various clinical settings of immune thrombocytopenia. All platelets were fully hemostatic and clinically no difference could be observed. This indicates that the effect of HDIg cannot be due to FcR blockade alone. PMID- 3094135 TI - Acute myelomonocytic leukaemia and acquired haemophilia A with severe cutaneous haemorrhage. AB - A case of severe cutaneous haemorrhage due to thrombocytopenia in combination with an acquired haemophilia A is reported. The thrombocytopenia was due to acute myelomonocytic leukaemia (FAB M4). A factor VIII:C specific anticoagulant was also found. Chemotherapy led to complete remission with normal blood counts and coagulation-test results. PMID- 3094136 TI - Immune responses during human schistosomiasis mansoni. XIII. Immunological status of spleen cells from hospital patients with hepatosplenic disease. AB - Splenocytes from 25 patients with severe hepatosplenic schistosomiasis mansoni were obtained after therapeutic splenectomy. Spleen cells were phenotyped and analysed for responsiveness to mitogens or heterogeneous schistosome-derived antigenic preparations (eggs, SEA; adult worms, SWAP; cercariae, CERC) in blastogenesis assays and lymphokine production systems, and were compared with peripheral blood mononuclear cells (PBMN). Splenic lymphocytes were 55% T lymphocytes (sheep erythrocyte rosette-positive) and 37% surface immunoglobulin positive B lymphocytes. The mean T4+:T8+ ratio of these splenocytes was 1.0. Phytohaemagglutinin stimulated spleen cell production of the lymphokine mitogenic factor, but exposure to SEA or SWAP did not. Spleen cell and PBMN blastogenic responses to SEA and SWAP were sometimes, but not always in accord. Removal of plastic adherent cells allowed the non-adherent spleen cells of 30-40% of the patients to respond substantially more vigorously to SEA, SWAP and CERC. Spleen cells from a subgroup of 20-30% of the patients failed to respond to the schistosomal antigens regardless of removal of adherent cells. Spleen cell responses to gram-negative lipopolysaccharide peaked on day 5 or 6 of culture, and were augmented by adherent cell removal. Pokeweek mitogen-stimulated responses were optimal on day 5 of culture. Spleen cells from most severe, hepatosplenic schistosomiasis mansoni patients do not respond well to schistosomal antigens or B-cell mitogens. The splenic responses of many of these patients were elevated by the removal of adherent spleen cells. PMID- 3094137 TI - Evaluation of beta-lactamase activity and microbial interference in treatment failures of acute streptococcal tonsillitis. AB - Out of 169 patients with streptococcal tonsillitis treated with phenoxymethylpenicillin, 13 (8%) developed a new clinical infection with the same streptococcal strain within 2 weeks of completing the therapy (clinical treatment failure) and 24 (14%) were clinically healthy but harboured the same streptococcal strain after treatment (bacterial treatment failure). Patients with clinical treatment failure showed beta-lactamase activity in their saliva pellet significantly more often than patients with bacterial treatment failure, healed streptococcal tonsillitis or non-streptococcal tonsillitis as well as healthy controls. In an interference study, clinical treatment failures were compared with healthy streptococcal carriers, i.e. persons living in the same household and harbouring the same beta-streptococcal strain. 11/12 healthy carriers had alpha-streptococci with interfering activity against their own beta-streptococcal strain, while the corresponding figure for the clinical treatment failures was 2/13. Furthermore, 6/12 healthy carriers had beta-streptococci inhibiting their own alpha-strains, while the streptococci in 11/13 clinical treatment failures had this ability. The beta-lactamase activity and the interference between alpha- and beta-streptococci may be a contributory cause to treatment failure in streptococcal tonsillitis. PMID- 3094138 TI - Detection of bacterial antigens in body fluids by the Phadebact system. AB - 150 infected patients from 2 study centers had body fluids examined for presence of bacterial antigens (group B streptococcus, Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b) using the Pharmacia Phadebact system. The rates of detection of the pneumococcal antigens in the urine or serum of the patients with pneumococcal pneumonia, pneumococcal bacteremia and pneumococcal meningitis were 0.38, 0.47 and 0.5, respectively. The overall detection rate for H. influenzae infections was 0.92 and for group B streptococcal infections 0.87. Serum and urine from 100 non-infected patients were also tested for the presence of group B streptococcus, S. pneumoniae, N. meningitidis and H. influenzae type b antigens with only 1 false positive (H. influenzae type b). PMID- 3094139 TI - Imipenem/cilastatin versus gentamicin/clindamycin: a cost effectiveness study. AB - A previously published clinical trial was used for analysis of costs for antibiotic treatment in patients with serious bacterial infections requiring the use of injectable broad spectrum antibiotics. The patients were randomized to receive imipenem/cilastatin 500/500 mg q6h (77 patients of which 56 were evaluable for efficacy) or clindamycin 600 mg q6h plus gentamicin 1.5 mg/kg with dose intervals determined by serum concentration monitoring (86 patients of which 62 were evaluable for efficacy). An analysis of the costs for antibiotics, including drugs, equipment and staff for administration and gentamicin serum concentration assays, showed that imipenem/cilastatin was not more expensive than gentamicin plus clindamycin per treatment day although the drug cost was considerably higher for imipenem/cilastatin. Since imipenem/cilastatin was significantly more effective and caused less frequent adverse reactions than gentamicin plus clindamycin it was more cost-effective in the patients studied. PMID- 3094140 TI - [Esophageal obstruction in tube feeding: a result of protein precipitation caused by antacids?]. AB - A complication of tube feeding, i.e. thickening of nutrient solution in the presence of an antacid leading to obstruction of the esophagus, is reported. Three patients on artificial breathing where fed by tube with Fresubin liquid. At intervals, Alucol liquid was given for stress ulcer prevention through the tube. After 2, 4, and 50 days respectively, reflux of nutrient solution into the mouth occurred. On removal of the tube a compact, yellowish-white substance was extracted. Endoscopically, residual particles were found in the upper part of the esophagus and in the hypopharynx which obstructed the esophagus completely and in one case could only be extracted through a rigid esophagoscope. In vitro studies showed that thickening of the nutrient solution was due to interaction with antacids administered simultaneously with the nutrient. PMID- 3094141 TI - [Thrombolysis in acute myocardial infarct: prerequisites, current experiences and remaining problems]. AB - Left ventricular pump failure is today's main cause of in-hospital mortality from acute myocardial infarction and is directly dependent on infarct size. The first clinical attempts to preserve myocardium after acute infarction and to improve morbidity and prognosis by thrombolysis date from about twenty years ago. Through large multicenter studies and promising new agents, coronary thrombolysis has again attracted increased attention in the past two years. After a brief overview on the preconditions for successful thrombolysis, the efficacy, advantages, complications and problems of different thrombolytic agents and forms of administration are reviewed on the basis of the controlled studies published up to June 1986. They concern streptokinase by intracoronary and intravenous route, urokinase and the "clot specific" agents of the second generation, recombinant tissue-type plasminogen activator (rtPA) and anisoylated plasminogen streptokinase activator complex (APSAC) BRL 26921. Finally, questions that remain open even after successful thrombolysis with myocardial salvage are raised, and in particular the problem of reocclusion and postlytic treatment. In spite of justified hopes and the demonstrable feasibility of reopening a coronary artery, thrombolysis in acute myocardial infarction should not be used routinely as long as the beneficial long term effect is not definitely proven for patients, or at least for a known subgroup of patients, in terms of left ventricular function, mortality and morbidity following myocardial infarction. PMID- 3094142 TI - [Meningococcal epidemic in a boarding school: a rifampicin-resistant secondary case while under chemoprophylaxis]. AB - An epidemic of meningococcal disease after an influenza outbreak in a community of 49 boys (14-18 years) and 8 adults in a boarding-school is reported. The first patient died with all symptoms of the Waterhouse-Friderichsen syndrome. Several hours later, two other boys developed severe septicemia with meningitis and meningitis respectively. N. meningitidis group B susceptible to penicillin and rifampin was isolated. Within the next 8 hours, chemoprophylaxis with rifampin (600 mg twice daily) was started and maintained for 4 days for the whole community. Throat cultures had not been obtained before prophylaxis. Ten other symptomatic boys were admitted to the hospital and treated by penicillin infusion. The results of blood and cerebrospinal fluid cultures were negative, and treatment was therefore discontinued. Five days after the death of the first boy, another boy died with full-blown Waterhouse-Friderichsen syndrome while on chemoprophylaxis. The neisseriae isolated from this patient were rifampin resistant. Serological investigations in all patients admitted to hospital revealed the existence of concomitant epidemic infection with influenza A and B in this school. We assume that the viral infection made way for the outbreak of the meningococcal disease and for the high rate of secondary meningococcal infection. Chemoprophylaxis with rifampin should not be continued for longer than 2 to 3 days, otherwise the risk of occurrence of rifampin resistant strains of N. meningitidis increases. Hitherto such strains have rarely been isolated in clinically manifest disease. PMID- 3094143 TI - [Post-transfusion hepatitis in the Zurich region]. AB - In the years 1979 to 1983 approximately 350,000 units of blood were transfused in the area of Zurich. During the same period 45 cases of posttransfusion hepatitis were reported. In 12 of these cases transfusion could be excluded as cause of the hepatitis. In another 26 cases it was not possible to prove a connection between the blood transfusion and the hepatitis. Only in 7 cases was blood transfusion proved to be responsible for posttransfusion hepatitis: in 3 cases blood positive for HBs-Ag was transfused. In 3 other cases donors who had donated HBs-Ag negative blood developed hepatitis-B shortly after their blood donation: it is assumed that their blood at the time of donation was carrying infectious hepatitis-B-virus particles at a concentration too small to be detected by routine HBs-Ag screening. In one case only was transmission of non-A-non-B hepatitis virus suspected. Due to improved HBs-Ag-screening, the incidence of posttransfusion hepatitis has been reduced by nearly 70% during the last 10 years. Nevertheless, efforts must continue to reduce the incidence of this important transfusion complication. PMID- 3094144 TI - Identification of paramyosin as schistosome antigen recognized by intradermally vaccinated mice. AB - Mice immunized intradermally with extracts of Schistosoma mansoni in combination with the adjuvant BCG are significantly protected against subsequent infection with living larval forms of the parasite. Remarkably, these vaccinated animals produce antibodies predominantly against a single parasite protein of molecular weight 97 kilodaltons (Sm-97). A complementary DNA that encodes about half of the Sm-97 molecule has now been cloned and sequenced. Analysis of the deduced amino acid sequence reveals a protein containing periodic repeats of hydrophobic amino acids characteristic of an alpha-helical coiled-coil structure. The deduced amino acid composition of the cloned gene and several properties of the native protein are similar to that of paramyosin, an alpha-helical protein that forms the core for myosin filaments in invertebrate muscle. Paramyosin was isolated from Schistosoma mansoni adult worms and antibodies to Sm-97 were shown to react with this molecule as well as with a known paramyosin from molluscan muscle. PMID- 3094145 TI - Trypanosoma cruzi infection inhibited by peptides modeled from a fibronectin cell attachment domain. AB - The mechanism by which Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, becomes attached to mammalian cells is not well understood. Fibronectin is thought to participate in the attachment, and in this study the region of fibronectin that interacts with the surface receptors of T. cruzi trypomastigotes was investigated by testing the binding of the amino acid sequence Arg-Gly-Asp-Ser, corresponding to the cell attachment site of fibronectin to T. cruzi trypomastigotes. Peptides with the sequence Arg-Gly-Asp Ser, but not Arg-Phe-Asp-Ser, Arg-Phe-Asp-Ser-Ala-Ala-Arg-Phe-Asp, Ser-Lys-Pro, Glu-Ser-Gly, or Ala-Lys-Thr-Lys-Pro, bound to the parasite surface and inhibited cell invasion by the pathogen. Monoclonal antibodies to the cell attachment domain of fibronectin also inhibited cell infection by the parasite. The immunization of BALB/c mice with tetanus toxoid-conjugated peptide induced a significant protection against T. cruzi. The data support the notion that the sequence Arg-Gly-Asp-Ser of cell surface fibronectin acts as a recognition site for attachment of the parasites. PMID- 3094146 TI - Isolation and sequence of L3T4 complementary DNA clones: expression in T cells and brain. AB - T lymphocytes express on their surface not only a specific receptor for antigen and major histocompatibility complex proteins, but also a number of additional glycoproteins that are thought to play accessory roles in the processes of recognition and signal transduction. L3T4 is one such T-cell surface protein that is expressed on most mouse thymocytes and on mature mouse T cells that recognize class II (Ia) major histocompatibility complex proteins. Such cells are predominantly of the helper/inducer phenotype. In this study, complementary DNA clones encoding L3T4 were isolated and sequenced. The predicted protein sequence shows that L3T4 is a member of the immunoglobulin gene superfamily. It is encoded by a single gene that does not require rearrangement prior to expression. Although the protein has not previously been demonstrated on nonhematopoietic cells, two messenger RNA species specific for L3T4 are found in brain. The minor species comigrates with the L3T4 transcript in T cells, whereas the major species is 1 kilobase smaller. PMID- 3094147 TI - The structure of immunoglobulins and their genes, DNA rearrangement and B cell differentiation, molecular anomalies of some monoclonal immunoglobulins. PMID- 3094148 TI - Laboratory monitoring of myeloma proteins. PMID- 3094149 TI - Clinical implications of monoclonal light chains. PMID- 3094150 TI - Monoclonal immunoglobulins with antibody activity in myeloma, macroglobulinemia and related plasma cell dyscrasias. PMID- 3094151 TI - The clinical implications of monoclonal immunoglobulins. PMID- 3094152 TI - [Myasthenia gravis]. PMID- 3094153 TI - [Behavior of the family facing a childhood asthmatic crisis]. PMID- 3094154 TI - [Administration of intravenous anticancer drugs. Some directions]. PMID- 3094155 TI - [Confronting diarrhea on a worldwide scale]. PMID- 3094156 TI - [Treatment of diarrhea]. PMID- 3094158 TI - [Control of pain in the terminal phase of cancer]. PMID- 3094157 TI - [At what point does diarrhea become harmful?]. PMID- 3094159 TI - Pinemoth caterpillar disease. AB - Pinemoth caterpillar disease is a well-recognised disorder which occurs in South Eastern China and is due to contact with the cocoons or larvae of the pinemoth (Dendrolimus punctatus). Generalised symptoms, which may be noted within two weeks of contact, consist of pyrexia, anorexia, malaise, rigors, headache, or dizziness. Localised abnormalities include dermatologic changes, skin nodules, and arthritis. The arthritis is usually monoarticular and most frequently involves the knee, ankle, and wrist. The radiologic findings consist of periarticular swelling, osteoporosis, erosions, or periosteal reaction in the acute phase and osseous sclerosis, joint deformity, persistent soft tissue swelling, or premature fusion of ossification centers in the chronic stages. PMID- 3094160 TI - Case report 384: Paraparesis from cauda equina compression due to disc herniation of L4-L5, in a patient with ossification of the posterior longitudinal ligament (OPLL) at L4-L5 and C4-C5. PMID- 3094161 TI - Case report 385: "Horned crests": pseudo-Fong syndrome. PMID- 3094162 TI - Utilization of health services in Indonesia. AB - This paper examines the utilization patterns of traditional and modern health services in Indonesia, using household sample survey socio-economic data in conjunction with community-level data on availability of services. The results strongly suggest that low household income is a barrier to the utilization of modern health services, even where they are publicly provided. The relatively well-to-do use the services of trained practitioners and physicians more and spend more on these services than do the poor. That is, income has a qualitative effect shown as a shift to more expensive and sophisticated practitioners and services rather than increased expenditures on the same type of services. Nevertheless, public facilities do make a difference; where they are available people prefer them to indigenous practitioners. Despite limitations of data and method of estimation, it is clear that both income and availability of services matter and hence that public services are more important to the poor than to the rich. The results further suggest that exposure to modern services that may involve health education brings about the right kinds of substitutions from an efficiency viewpoint: paramedics for traditional practitioners as well as physicians. PMID- 3094163 TI - [Program of medicalization of the information system]. PMID- 3094164 TI - [Parenteral feeding in infants. Hepato-biliary complications]. PMID- 3094165 TI - Elevated pleural fluid glucose: a risk for tension hydrothorax. AB - We have presented a case of tension hydrothorax that developed after hyperosmolar hyperalimentation fluids were infused into the pleural space through a misplaced jugular venous line. The hyperosmolar state of the pleural fluid appears to have played a prominent role in the development of the tension hydrothorax. We believe there is a risk of tension hydrothorax in any clinical situation in which the pleural fluid glucose concentration is significantly higher than the serum concentration. PMID- 3094166 TI - [Socioeconomic and medico-organizational aspects of the outpatient diagnosis of surgical pathology of the lungs and mediastinum]. PMID- 3094167 TI - [A radionuclide method of examination after decompression of the biliary tract]. PMID- 3094168 TI - Natural and synthetic heat shock protein gene promoters assayed in Drosophila cells. AB - Hybrid genes containing mRNA encoding sequences for herpes virus thymidine kinase (tk), chloramphenicol acetyltransferase (CAT), or Drosophila alcohol dehydrogenase (Adh), ligated to truncated Drosophila melanogaster heat-shock protein 70 (hsp 70) gene promoters or to synthetic sequences containing one or several copies of a previously defined heat-shock consensus sequence, were transfected into cultured Drosophila line S3 cells. Each construction was then assayed for gene expression at 25 degrees C and 37 degrees C, using a CAT enzyme assay, slot blot hybridization, or S1 nuclease protection analysis. In the Drosophila cell transient expression assay system, we found that deletions extending beyond position -97, or synthetic constructions containing a single heat shock consensus sequence, were not induced by high-temperature shock. In constructions containing deletions extending to position -186, -130, or -97, in the hsp 70 promoter, and in synthetic constructions containing tandemly spaced heat-shock consensus sequences mRNA transcription was greatly induced by high temperature. PMID- 3094169 TI - [Advantages of Noxyflex in the treatment of severe diffuse peritonitis]. PMID- 3094171 TI - Misdiagnosis of sarcocystosis as giardiasis. PMID- 3094170 TI - [Cricopharyngeal myotomy in the treatment of parapharyngeal diverticula (experience with 54 surgically treated patients)]. PMID- 3094172 TI - Treatment of infection due to penicillinase-producing Neisseria gonorrhoeae with oral thiamphenicol and with oral lymecycline. AB - Seventy-five men with gonococcal urethritis were treated with a single oral dose of thiamphenicol, and 88 men with this infection were treated with two 1.5-g oral doses of lymecycline taken 12 hr apart. Of the 75 subjects treated with thiamphenicol, 72 (96%) were cured, as compared with 80 (91%) treated with lymecycline. Sixty subjects (37%) were infected with penicillinase-producing Neisseria gonorrhoeae. In this group, 28 (97%) of 29 subjects treated with thiamphenicol were cured, as compared with 29 (94%) of 31 subjects treated with lymecycline. Patient compliance with the two-dose regimen was excellent, and no adverse effects occurred with either drug. Lymecycline may therefore be an effective alternative to thiamphenicol in those countries where strains of N. gonorrhoeae remain sensitive to the tetracyclines. PMID- 3094173 TI - Treatment of uncomplicated gonorrhea with ceftriaxone: a review. AB - Of the currently recommended regimens for treatment of uncomplicated gonorrhea, only aqueous procaine penicillin G is effective against infections of all sites. However, this agent is not effective against penicillinase-producing Neisseria gonorrhoeae and suffers from poor patient acceptability owing to the 10-ml volume of injection and to allergic and toxic reactions to procaine. Ceftriaxone is a new, extended-spectrum cephalosporin with a long serum half-life and is many times more active than penicillin G against both beta-lactamase-positive and negative strains of N. gonorrhoeae. In clinical trials ceftriaxone, in a single intramuscular dose of 125 or 250 mg, has proved as effective as any other regimen in the treatment of uncomplicated gonococcal infections of the pharynx, anorectum, cervix, and urethra. Thus, ceftriaxone (125 mg) should be considered a drug of choice for uncomplicated gonorrhea, particularly where homosexual men are treated and penicillinase-producing N. gonorrhoeae and/or chromosomally mediated resistance is prevalent. PMID- 3094175 TI - Body compositional changes in cancer patients. AB - Noninvasive and spectroscopic techniques already available and under further development in several laboratories will in the near future give us a greater amount of detailed information on changes in body compartments in disease and in response to therapeutic efforts. Such techniques should have the ability to measure directly components in an organ or tissue in contrast to most present and previous techniques that generally rely on derivation of components from a few direct measurements. Such derivations are unfortunately dependent on assumptions that are not possible to control in several circumstances. PMID- 3094174 TI - Treatment of gonorrhea with first- and second-generation cephalosporins and other new beta-lactam antibiotics. AB - Aqueous procaine penicillin, ampicillin, and amoxicillin have been used successfully in treatment of gonococcal infections for many years. Many of the new beta-lactam antimicrobial agents subsequently have proved effective for treating these infections as well. First-generation cephalosporins are less active (by weight) than second-generation cephalosporins, which, in turn, are less active than third-generation drugs. Single-dose therapy of uncomplicated mucosal gonococcal infections with first-generation cephalosporins has resulted in generally unacceptably low cure rates of less than 90% in most studies, whereas parenterally and orally administered second-generation cephalosporins show good clinical efficacy. Both second- and third-generation cephalosporins are active against beta-lactamase-producing Neisseria gonorrhoeae. The extended spectrum and ureido-penicillins are active in vitro against non-beta-lactamase producing N. gonorrhoeae and have parallel activity in vivo. Single doses of aztreonam, the first monobactam studied in humans, have also shown excellent clinical efficacy. PMID- 3094176 TI - Adverse metabolic consequences of nutritional support: macronutrients. AB - The administration of a complete and well-balanced diet commensurate with the requirements and limitations of individual patients is essential to obtain maximal benefit of nutritional therapy. Complications related to the provision of nutritional therapy must be considered when providing nutrition support to patients with malignant diseases. Some of these complications are not exclusive of the form of therapy, whereas others are inherent in the different components of nutrient solutions used. A sound knowledge of clinical nutrition as well as the establishment of nutrition support teams will help to reduce the incidence of adverse reactions related to the nutritional treatment. Further research is necessary to understand better the mechanisms of malnutrition in cancer patients and the mechanisms by which several organs and systems are adversely affected during nutrition support. New methods and devices will lead to a more efficacious administration of nutritional requirements. PMID- 3094177 TI - Adverse metabolic consequences of nutritional support: micronutrients. AB - The role of total parenteral nutrition in cancer patients is still a matter of controversy. Over the last decade there has been a heightened interest in the interaction of micronutrients with tumor cells. A review of the literature reveals that the question of feeding or suppressing the tumor by supplementing micronutrients remains unanswered. Prospective studies are needed to define the requirements of vitamins and trace elements in the cancer patient. PMID- 3094178 TI - Cancer and protein metabolism. AB - We have reviewed the data that indicate that protein depletion is an important problem in cancer patients. An incomplete, yet useful, idea of the underlying mechanisms emerges. Further, we have seen that the provision of nutritional support may have a beneficial effect on patients with cancer, and we have explored areas of recent advances in nutritional formulation as regards energy and nitrogen source. Finally, data regarding micronutrients affecting nitrogen metabolism were reviewed. The extent to which tumor metabolism and changes secondary to the tumor-bearing state are influenced by micronutrients is not known. Traditional regimens based on the requirements of normal subjects or noncancer patients may not be relevant to the metabolic needs of the cancer patient. This could explain in part the failure of nutritional intervention trials to demonstrate a consistent benefit of nutritional support to the cancer patient. Further information regarding micronutrient needs in normal humans and cancer-bearing patients and their utilization by malignant tumors will have to be obtained. PMID- 3094179 TI - Body protein kinetics during perioperative intravenous nutritional support. AB - The kinetics of whole body protein metabolism in eight patients with benign disease were evaluated during perioperative isocaloric and isonitrogenous intravenous feedings. A prime infusion of 15N-glycine with determination of urinary end product enrichment and stochastic analysis was used to determine protein kinetics. Surgically induced increases in body protein turnover, synthesis and breakdown were evident on the fifth postoperative day. Abdominal operation was associated with a rise in urinary 3-methylhistidine (3MH) excretion. The postoperative alteration in the relationship between 3MH excretion and body protein breakdown suggests that even mild to moderate surgical injury induces tissue specific changes in protein metabolism. Resting energy expenditure remained unchanged from that of the preoperative levels on the fifth postoperative day. Despite significant changes in body and tissue specific protein kinetics, there is no change in the apparent efficiency of oxygen use for protein homeostasis postoperatively. The failure to observe a relationship between energy expenditure and protein metabolism suggests that only a small proportion of body oxygen uptake is directed toward protein homeostasis after elective surgical procedures. A comparison of perioperative complete intravenous feeding to hypocaloric regimens will be necessary to evaluate more fully the impact of protein and energy balance upon cellular and body protein homeostasis after injury. PMID- 3094180 TI - One hundred and fourteen fistulas of the gastrointestinal tract treated with total parenteral nutrition. AB - During a period of five years, all patients with fistulas of the gastrointestinal tract who received total parenteral nutrition as a part of the therapy were evaluated retrospectively. One hundred and eight patients with 114 fistulas of the gastrointestinal tract were studied. There were 58 male and 50 female patients. The mean age of the patients was 58 years old. Fifty-one per cent (58) of all fistulas resulted from surgical complications and 30 per cent from inflammatory disease. The most common origin of the fistula was the small intestine (48 per cent), with the large intestine being the next most common origin (26 per cent). Ninety-eight of the fistulas were treated successfully. The mean time for closure from the time of diagnosis was 30.9 days. Sixty-one per cent (69) of all fistulas closed spontaneously, the use of parenteral nutrition resolved 37 per cent (42) and 24 per cent (27) resolved after surgical control of sepsis. Twenty-five per cent (29) of the fistulas required definitive surgical closure. Sixteen patients died prior to resolution of the fistula, 11 deaths were directly related to septic complications of the fistula and one died as a result of hemorrhage of the fistula tract. The direct fistula-related mortality rate was 10.5 per cent. Whereas the mortality rate for fistulas remained stable, spontaneous closure rates continue to improve. This is attributed to improved "para-surgical" care, appropriate nutritional support and early and aggressive control of sepsis. Ninety to 95 per cent of fistulas that spontaneously resolve will do so within four to five weeks. Inflammatory disease of the intestine and radiation induced fistulas continue to respond poorly to medical management. PMID- 3094181 TI - Rapid replacement of serum albumin in patients receiving total parenteral nutrition. AB - The albumin deficit (AD) of 13 malnourished patients with serum albumin concentrations (SAC) of less than 3.0 grams per deciliter was estimated using a simple equation. The AD was replaced over a period of 24 to 72 hours as a component of the formulation of total parenteral nutrition (TPN). AD was estimated assuming a volume of distribution of 3 deciliters per kilogram of actual body weight and a minimum acceptable SAC of 3.5 grams per deciliter. The mean AD was 200 +/- 94 grams (mean +/- standard deviation), the average dose administered was 206 +/- 97 grams. TPN regimens provided 42.0 +/- 8.5 nonprotein kilocalories per kilogram with a nonprotein calorie to nitrogen ratio of 125 to 150:1. The SAC increased from 2.36 +/- 0.38 grams per deciliter to 3.46 +/- 0.26 grams per deciliter immediately after replacement. At follow-up study, the SAC at 6.4 +/- 1.5 days yielded a SAC value of 3.35 +/- 0.30 grams per deciliter, indicating no significant decrease from immediate replacement values. AD can be easily estimated, rapidly replaced and maintained with adequate nutritional support. PMID- 3094182 TI - A requiem for the routine operative cholangiogram. PMID- 3094183 TI - Nontumoral aqueductal stenosis in children affected by von Recklinghausen's disease. AB - The authors report three cases of primary nontumoral aqueductal stenosis associated with von Recklinghausen's disease in children. Moreover, 16 similar cases collected from the literature are presented. The clinical features are evaluated in light of data from the literature. Among all 19 cases, the median age was 19 years (range 6-46 years), and nine patients were under the age of 13 years. Our own patients underwent ventriculoatrial shunt procedures, followed by clinical recovery (follow-up 2-5 years). In one patient, computed tomography scanning performed 20 months after the operation showed a chronic calcified subdural hematoma in the right frontoparietal area. In conclusion, it is felt that, among all the pathological events usually described in patients affected by neurofibromatosis, primary aqueductal stenosis seems to be part of the natural history of this neurological syndrome. PMID- 3094184 TI - [First results of high-dose-rate 192-Iridium afterloading method applied alone or associated with laser therapy in tumors of the respiratory and digestive tracts]. AB - High-dose-rate short-term brachytherapy with 192iridium, preceded by laser therapy if practicable, has been applied in an interdisciplinary collaboration for more than one year at our hospital. Until April, 1985, 127 applications have been made in 49 patients suffering from tumors of the respiratory and upper digestive tract. The palliative effects obtained (74% and 86%, respectively) correspond with those achievable by percutaneous radiotherapy. The local control rates can possibly be improved by an 192iridium boost in the course of a curative radiotherapy. PMID- 3094186 TI - Hepatic steatosis in total parenteral nutrition: failure of fatty infiltration to correlate with abnormal serum hepatic enzyme levels. AB - Total parenteral nutrition (TPN) is associated with hepatic biochemical and morphologic changes. Suggested causes include excessive glucose calories, fatty acid deficiency, and enterically derived hepatotoxins escaping atrophied bowel. Male Sprague-Dawley rats were cannulated or sham operated with internal jugular ligation. The cannulated groups received TPN with a 25% dextrose base, or TPN 12.5% dextrose and given nothing by mouth, or saline solution and allowed to eat ad lib. Sham animals ate ad lib. After 6 days the animals were killed and portal blood was assayed for endotoxin and cultured. Cultures were also taken of the liver. Serum hepatic enzyme concentration and hepatic fat were determined. All cultures and endotoxin assays were negative. Microscopy revealed nonlipid vacuolization in both TPN groups, a finding reproduced by direct portal infusion of endotoxin. There was significant hepatic steatosis in the 25% dextrose base TPN versus all other groups (28.6% liver weight versus 6.3% liver weight; p less than 0.05). This was correlated with caloric intake (28.7 calories/100 gm/day versus 21.2 calories/100 gm/day; p less than 0.05). Liver enzymes were not significantly different among groups. We conclude that hepatic steatosis in TPN is a result of overfeeding a glucose only substrate and that fatty infiltration is independent of changes in blood hepatic enzyme concentrations. Although other morphologic changes of hepatotoxin-induced injury were seen in the TPN group, portal endotoxemia to the level of 1 ng/ml could not be documented. PMID- 3094185 TI - Partial correction by exogenous lipid of abnormal patterns of polyunsaturated fatty acids in plasma phospholipids of stressed and septic surgical patients. AB - Polyunsaturated fatty acid (PUFA) profiles are abnormal in a variety of clinical conditions that are commonly seen in the surgical intensive care unit. PUFA profiles in the serum phospholipids were studied by capillary gas chromatography in 22 critically ill, hypermetabolic surgical intensive care unit patients. All patients received continuous total parenteral nutrition (TPN) by central vein with trace elements and vitamins. Eleven patients received daily supplementation with 50 gm of safflower oil-based lipid emulsion (TPN + L group). No lipid was administered in the other 11 patients (TPN). Both groups showed deficiencies in 18:2 omega 6 linoleic acid from the time of onset of TPN. In TPN the deficiency was progressive; in the TPN + L group, lipid administration prevented this progression but did not restore 18:2 omega 6 levels to normal. In the TPN group levels of 18:1 omega 9 and its metabolite 20:3 omega 9 (the triene of deficiency) increased over time, consistent with a mild essential fatty acid deficiency. These changes in omega 9 acids were not seen with lipid supplementation. Despite low levels of 18:2 omega 6 in both groups, the levels of omega 6 metabolites were normal or increased. Levels of 20:4 omega 6 (arachidonate) remained normal or slightly decreased in the TPN group but were decreased in the TPN + L group. Levels of arachidonate metabolites, in particular 22:5 omega 6, were increased in the lipid-supplemented group. We concluded that stressed patients receiving TPN develop mild essential fatty acid deficiency that is only partially correctable by lipid supplementation and that administration of supplemental lipid to these patients stimulates arachidonic acid conversion to 22:5 omega 6. PMID- 3094187 TI - [Effectiveness of 2 drug forms of nitroglycerin--transdermal (preparation Nitroderm-TTS) and gingival application (preparation Trinitrolong)--in ischemic heart disease patients]. PMID- 3094188 TI - [Rare causes of secondary gout]. PMID- 3094189 TI - [Clinico-functional and morphological characteristics of the stomach in Sjogren's disease]. AB - Stomach secretory function and gastrin concentration in the blood serum were studied in 45 patients with Sjogren's disease. A sharp decrease in acid- and enzymoforming function of the stomach, disorder of the process of mucus formation and hypergastrinemia were detected in 80% of the patients. The relationship of stomach secretory function, gastrin concentration and the gravity of xerostomia was established. Morphology of the mucosa of the body and antral part of the stomach revealed chronic atrophic gastritis. Massive lymphohistiocytic infiltration of the mucous membrane with focal aggregations of lymphoid elements, atrophy and destruction of the glands were revealed. B-lymphocytes prevailed in the cellular infiltrate. T-lymphocytes were found in a small amount among the infiltrate cells and epithelial cells of the main gastric glands. PMID- 3094190 TI - ATP-secretion occurs as an initial response in collagen induced platelet activation. AB - The time course and degree of collagen induced platelet shape change, aggregation and ATP-secretion in citrated human platelet rich plasma was monitored with a lumi-aggregometer. Onset of ATP-secretion was measurable within seconds after collagen challenge and always distinctly before onset of shape change. In absence of platelet aggregation, the degree of collagen stimulation was correlated to onset of secretion, the secretion rate and onset of subsequent shape change. It is concluded that the secretion originated from the collagen-adherent platelets. Oral aspirin [1000 mg] did neither delay onset of secretion nor reduce the final amounts of ATP indicating that formation of TxA2 is not a necessary prerequisite for dense granule secretion during the primary activation process. EDTA and EGTA decreased the initial secretion rate, but may have interfered with the adhesion process. Micromolar concentrations of verapamil and yohimbine also reduced secretion, while the effect of theophylline was 100 times weaker. The results suggest that the primary activation process is vulnerable at the alpha-receptor level and that the initial ATP-secretion requires Ca2+-entry rather than intra platelet Ca2+-mobilization. PMID- 3094191 TI - Effects of Y-20811, a long-lasting thromboxane synthetase inhibitor, on thromboxane production and platelet function. AB - Effects of a new imidazole derivative, sodium 4-[alpha-hydroxy-5-(imidazolyl)-2 methylbenzyl]-3,5-dimethyl benzoate dihydrate (Y-20811), on thromboxane (TX) production and platelet aggregation were investigated. Y-20811 inhibited TX synthetase (IC50 = 2.2 X 10(-8) M) and platelet aggregation induced by arachidonic acid (AA) in human, guinea pig and rabbit platelets in vitro. Administered orally to rabbits, Y-20811 at a dose of 1 mg/kg decreased serum TXB2 concomitant with increasing 6-keto PGF1 alpha and at a dose of 3 mg/kg inhibited AA-induced platelet aggregation, in both cases for at least 48 hours. Y-20811 (0.3 mg/kg/day) administered to rabbits for 7 days decreased serum TXB2 levels by 50-90% during the medication, and these levels were restored to initial values 3 days after withdrawal of the drug. At a dose of 1 mg/kg Y-20811 protected rabbits against death induced by AA (2 mg/kg). These results indicate that Y-20811 is a selective and long-lasting TX synthetase inhibitor and an anti-aggregating agent useful in preventing thrombotic disorders. PMID- 3094192 TI - The effect of EDTA on the production of prostacyclin by rat aorta. PMID- 3094193 TI - Turnover of human tissue plasminogen activator (tPA) in rabbits. AB - The turnover of purified tissue plasminogen activator (tPA) from two different manufacturers was compared in rabbits. The first was melanoma derived one-chain tPA and the second was recombinant two-chain tPA. No differences were noted between the two products. A biphasic disappearance curve was observed for the protein (125Iodine labelled). The first phase was extremely rapid with a T1/2 of 0.59-0.89 min; the secondary phase had a T1/2 of 10-12 min. tPA accumulated rapidly in the liver (44% at twenty min) and appeared to be degraded as demonstrated by the increase in plasma of low molecular weight material which was also TCA soluble. Fractionation of purified recombinant two-chain tPA on a Dupont GF-250 column yielded two peaks of protein (Peak 1 and Peak 2) and the turnover of each in rabbits was compared. PMID- 3094194 TI - Binding of a metabolite of 3,4,3',4'-tetrachlorobiphenyl to transthyretin reduces serum vitamin A transport by inhibiting the formation of the protein complex carrying both retinol and thyroxin. AB - The mechanism of serum vitamin A reduction by polychlorinated biphenyls was studied at the level of the plasma transport protein system for vitamin A. Analysis of [3H]retinol-labeled serum proteins by polyacrylamide gel electrophoresis (PAGE) showed association of retinol with two proteins that were identified as retinol binding protein (RBP) and the RBP complex with transthyretin (TTR). The amount of [3H]retinol radioactivity in the serum as well as the label associated with the binding proteins was strongly reduced by 3,4,3',4'-tetrachlorobiphenyl (TCB). A possible interaction of TCB with the retinol binding proteins was investigated, using radiolabeled TCB. Analysis of the plasma proteins by PAGE revealed the presence of four peaks of 3H-TCB label, the major ones being associated with lipoproteins and TTR. No 3H-TCB radioactivity was found in the region of the gel where RBP or the RBP-TTR complex was located. HPLC analysis of the radioactive compound associated with TTR showed the presence of a metabolite of TCB, rather than the parent compound. These data indicate a direct interaction of a metabolite of TCB with TTR leading to an inhibition of formation of the serum transport protein complex carrying both retinol and thyroxin. A model is proposed, which may explain certain characteristic toxicopathological lesions observed in species exposed to polychlorinated biphenyls and related compounds (TCDD, PBBs, etc.). PMID- 3094195 TI - Inhibition of methyl chloride toxicity in male F-344 rats by the anti inflammatory agent BW755C. AB - This study examined the effectiveness of the cyclooxygenase/lipoxygenase inhibitor 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW755C) in preventing the toxicity induced in male F-344 rats by methyl chloride (MeCl). BW755C (10 mg/kg ip, 1 hr pre and postexposure) prevented both lethality (0/6 vs 8/12 in controls) and epididymal granuloma formation (0/6 vs 4/4 in controls) in rats exposed to 7500 ppm MeCl 6 hr/day for 2 days. Additional rats (n = 5 per group) were exposed to 5000 ppm MeCl 6 hr/day for 5 days, with and without BW755C treatment as described above. The rats were killed on Day 5 and tissues processed for light microscopic examination. MeCl-exposed rats showed hepatocellular cloudy swelling, degeneration of renal proximal convoluted tubules, vacuolar degeneration in the adrenal cortex, necrosis of the internal granular layer of the cerebellum, and degenerative changes in the testis and epididymis, including formation of epididymal sperm granulomas. With the exception of the adrenal, tissues examined in rats of the MeCl/BW755C treatment group showed virtually no histologic evidence of lesions. BW755C did not significantly alter metabolism of [14C]MeCl to 14CO2 or 14C in urine, nor did it affect the distribution to various organs of radioactivity derived from [14C]MeCl. Therefore, BW755C protection against MeCl toxicity did not appear to result from altered MeCl metabolism or disposition. Instead, the protection was apparently related to the pharmacologic activity of BW755C as an inhibitor of leukotriene and prostaglandin synthesis. PMID- 3094196 TI - Effect of a mixed function oxidase inducer and inhibitor on monocrotaline pyrrole pneumotoxicity. AB - Monocrotaline (MCT) produces vascular injury to the lung, pulmonary hypertension, and right ventricular hypertrophy when injected into rats. It is well established that the pneumotoxicity of MCT depends on its hepatic bioactivation to monocrotaline pyrrole (MCTP) and perhaps other toxic metabolites. To test whether MCTP requires further bioactivation, we synthesized this metabolite chemically, confirmed its structure using fast-atom bombardment-mass spectrometry and nuclear magnetic resonance, and injected it into rats previously treated with an inducer or inhibitor of MFOs. Pretreatment with either phenobarbital or SKF-525A did not alter the pneumotoxic effects of an intravenous injection of MCTP. Rats given the same intravenous dose of either MCT, MCT N-oxide, or MCTP responded with toxicity only to MCTP. MCTP added to rat serum in vitro resulted in a color change (Amax = 477 nm) that developed over several seconds, an observation consistent with degradation of MCTP in serum. To explore the possibility that aqueous degradation products might contribute to its toxicity, the same intravenous dose of MCTP was administered to rats in N,N-dimethylformamide (DMF), serum, or saline. Only MCTP administered in in DMF resulted in toxicity. These results support the contention that MCT requires metabolism to MCTP to produce pneumotoxicity and that exposure to aqueous media renders MCTP incapable of causing lung injury. PMID- 3094197 TI - Nonenzymatic oxygen activation and stimulation of lipid peroxidation by doxorubicin-copper. AB - Addition of cupric sulfate to neutral solutions of doxorubicin resulted in spectrophotometric, fluorometric, and chromatographic changes indicative of a direct chemical interaction. Associated with these changes was a copper-dependent consumption of dissolved oxygen and a superoxide dismutase-sensitive reduction of ferricytochrome c, suggesting the liberation of superoxide free radicals. Addition of equimolar ethylenediaminetetraacetic acid (EDTA) completely inhibited, but did not reverse, the effect of copper on the spectrophotometric, fluorometric, and chromatographic properties of the drug. EDTA also abolished the copper-stimulated consumption of oxygen and reduction of ferricytochrome regardless of the time of addition. Oxygen-free radical formation by the drug copper complex was further implicated by the stimulation of lipid peroxidation, which was completely inhibited by adding EDTA. Inhibition by superoxide dismutase, catalase, and dimethyl urea implicates the involvement of assorted oxygen-free radicals in doxorubicin-copper stimulated lipid peroxidation. The data demonstrate that despite the implication of hydrogen peroxide and hydroxyl radicals in doxorubicin-copper stimulated lipid peroxidation, the immediate product of dioxygen reduction by the complex is superoxide-free radicals. The suggested occurrence of doxorubicin-copper complexes in vivo infers that nonenzymatic generation of oxygen-free radicals by the chelate may contribute to the mechanism of toxicity of doxorubicin and related anthraquinone anticancer agents observed clinically. PMID- 3094198 TI - Stability of metallothionein in gastric juice. AB - Metallothionein (MT), is presumably the major Cd-binding component of human food. It is not or only partially destroyed by cooking. To study whether MT is stable in gastric juice MT was incubated at various pH values with pepsin and human gastric juice in vitro. Above pH 3.5 nearly all Cd remained bound to the protein and Cd-MT was resistant towards proteolysis. At pH values of 2.5 and 1.7 the protein was digested to 80% and 100%, respectively. At pH 2.5 two Cd-containing peptides with 25-30 amino acids similar to the alpha-domain of the protein were detected. At pH 1.7 these fragments were further degraded to smaller peptides. The results indicate that the pH-dependent proteolytic degradation of Cd-MT depends on the metal content of the protein. Furthermore, the identical results obtained with pepsin and human gastric juice suggest that Cd-MT proteolysis occurs in vivo and will affect Cd resorption. PMID- 3094199 TI - Cigarette smoking, hypertension and the risk of subarachnoid hemorrhage: a population-based case-control study. AB - A case-control analysis is used to examine the relation of cigarette smoking, hypertension and the risk of subarachnoid hemorrhage in men and women aged 35-64 years. 45 men and 70 women with subarachnoid hemorrhage were identified as part of a large community based study of stroke, and the controls, 1017 men and 569 women, came from a survey of cardiovascular risk factors conducted in the same community. Cigarette smokers, after adjusting for age, had a significantly increased risk of subarachnoid hemorrhage compared with nonsmokers with relative risks of 3.0 for men and 4.7 for women. The strength of the risk increased with the amount smoked. The association remained significant for each sex after adjusting for hypertension. Those who both smoked and had a history of hypertension had an increased risk of subarachnoid hemorrhage of almost 15 fold compared to those who neither smoked nor had been treated for hypertension. The estimated population attributable risk of subarachnoid hemorrhage associated with cigarette smoking (43%) was greater than that of hypertension (28%) in this population. PMID- 3094200 TI - Cerebral venous blood gas tensions in elevated intracranial pressure. AB - Cerebral venous blood gas tensions were correlated with elevated intracranial pressure in spontaneously breathing dogs lightly anesthetized with nitrous oxide/halothane. Intracranial pressure was elevated by infusion of artificial cerebrospinal fluid into a lateral ventricle. Respiration and blood pressure were monitored. The results of these experiments indicate that cerebral venous carbon dioxide tension is increased in association with elevation in intracranial pressure. Moreover, it appears that cerebral venous pCO2 is effectively regulated at a mean of about 52 mm Hg over a wide range of intracranial pressure. PMID- 3094202 TI - Post-traumatic Bacillus cereus endophthalmitis. PMID- 3094201 TI - [The protease method of detecting rhesus antigens in liquid blood studies for forensic medicine purposes]. PMID- 3094203 TI - Concentrations of factor VIII-related antigen and factor XIII during open heart surgery. AB - Plasma levels of factor VIII-related antigen (fVIIIRA) and factor XIII S and A subunits (fXIIIS, fXIIIA) were assayed by counterimmunoelectrophoresis before, during, and after cardiopulmonary bypass (CPB) in patients with coronary artery and valvular heart disease to define the basis for clinical and laboratory abnormalities of hemostasis occurring in this form of surgery. During CPB, concentrations of fXIIIA dropped in both patient groups but returned to preoperative levels promptly after pump removal. In contrast, fVIIIRA and fXIIIS, which are not incorporated into the clot, remained unchanged even during fluid administration. These data provide evidence of a transient consumption coagulopathy as a feature of CPB. Hemodilution probably plays a secondary role in these changes. PMID- 3094204 TI - Inactivation of human T-cell lymphotropic virus, type III by heat, chemicals, and irradiation. AB - Infectivity of human T-cell lymphotropic virus, Type III (HTLV-III) was inactivated by heat more rapidly if in liquid medium than if lyophilized and more rapidly at 60 degrees than 56 degrees C. When HTLV-III was added to factor VIII suspension, then lyophilized and heated at 60 degrees C for 2 hours or longer there was elimination of 1 X 10(6) in vitro infectious units (IVIU) of virus. Much of the viral inactivation appeared to result from lyophilization. The application of water-saturated chloroform to the lyophilized material containing virus also resulted in elimination of infectivity. HTLV-III was efficiently inactivated by formalin, beta-propiolactone, ethyl ether, detergent, and ultraviolet light plus psoralen. The results are reassuring regarding the potential safety of various biological products. PMID- 3094205 TI - Experimental pancreatic allotransplantation in large animals. The role of donor kidney and cyclosporine in modifying rejection. AB - Experiments were carried out in outbred dogs and pigs to evaluate the relative immunogenicity of pancreatic islets and segmental pancreas grafts, and whether these could be ameliorated by transplanting a kidney simultaneously from the same donor animal. Various immunosuppressive regimens were also studied. Pancreatic islet allografts never normalized blood glucose in totally pancreatectomized recipients despite the use of cyclosporine (CsA) in high doses (40 mg/kg/day) and the simultaneous transplantation of a kidney from the same donor. These grafts which never "took" contrast sharply with the experience of pancreatic islet autografts prepared in the same way and inoculated into the spleen, which in all nine instances normalized blood glucose in pancreatectomized recipients. Segmental transplants were performed in swine with duct drainage into the jejunum. Totally pancreatectomized pigs died at 7.8 +/- 1.0 days. In recipients suppressed with low-dose azathioprine (Az) and prednisone (Pred) pancreas grafts alone were rejected in 12.9 +/- 10 days. Synchronous pancreas and kidney transplants treated similarly extended the mean survival of pancreatic grafts to 20 +/- 10 days--which, however, was not significant (P less than 0.1 greater than 0.05). Mean survival time of pancreatic grafts in recipients receiving CsA at 20 mg/kg/day and prednisone 1 mg/kg/day was 14 +/- 6.3 days. The combination of CsA 20 mg/kg/day, Az 2 mg/kg/day, and Pred 1 mg/kg/day prolonged the mean survival time to 39.8 +/- 22 days. These results allow us to conclude that: crude preparations of islet tissue invariably capable of normalizing blood sugar at day 4 when used as autografts failed to "take" despite the existence of alternative sources of antigen present in a well vascularized kidney from the same donor, and despite very high dosages of CsA; triple immunosuppressive therapy had synergistic effects on pancreatic allograft survival; and simultaneous transplantation of kidney and pancreas had little effect on survival times of the pancreas or the kidney. PMID- 3094206 TI - Natural killer cell subsets in long-term renal allograft recipients. A phenotypic and functional study. AB - Natural Killer cell subsets were studied in 39 long-term renal allotransplant recipients receiving conventional immunosuppression and 26 normal controls. Two color flow cytometry analysis was used to determine coexpression of 2 surface antigens known to allow a phenotypic and functional discrimination of NK cells- Leu-7 a marker of large granular lymphocytes, and Leu-11c directed against the FcgammaR. In 11 patients and controls, these NK cell subsets were compared with actual NK activity assessed by killing of K562 target cells. Our data clearly show that, in long-term kidney recipients, the absolute number of NK cells (Leu 11c+) is significantly decreased compared with that of the control group. Furthermore, the most cytotoxic NK cell subset (Leu-7-/Leu-11c+ phenotype) is markedly diminished in the transplant population, whereas the less cytotoxic subset (Leu-7+/Leu-11c+) is unchanged. Finally, actual NK cell activity closely correlates with both relative and absolute numbers of these 2 NK cell subsets. These data provide convincing evidence that NK activity is impaired in long-term kidney recipients because of a diminished number of NK effector cells. PMID- 3094207 TI - Morphometric analysis of cellular infiltration assessed by monoclonal antibody labeling in sequential human renal allograft biopsies. AB - The mononuclear cell infiltrate in a total of 279 human renal allograft biopsies was determined by a panel of monoclonal antibodies using an indirect immunoperoxidase technique. Two hundred and seventy-two biopsies were obtained from 83 patients randomly allocated to receive short-term cyclosporine (CsA) or conventional azathioprine and low-dose prednisolone (AP). Biopsies were obtained routinely at days 0 (control biopsies), 7, 21, 90, and 365, as well as at other times when clinically indicated. A further 7 patients on AP therapy were biopsied several years after transplantation (median: 6 years 1 month). Morphometric analysis of cryostat tissue sections using a point-counting technique has shown that the infiltration in rejecting grafts is significantly greater than in grafts with stable function. However, significant infiltration also occurs within the first week after transplantation in grafts with stable function. While this infiltrate diminishes with time, it remains significant even in grafts biopsied several years after transplantation. The infiltration with CsA treatment is significantly less than with AP therapy. The magnitude of the infiltrate therefore varies with time, graft status, and immunosuppression. In contrast the phenotypic composition of the infiltrate remains relatively constant in all biopsies after transplantation with T lymphocytes (CD3+), accounting for approximately 35% of infiltrating cells and CD8+ cells more common than CD4+. Monocytes and macrophages account for most of the remainder of the infiltrate. PMID- 3094208 TI - The influence of the pattern of inflammation and administration of steroids on class II MHC antigen expression in renal transplants. AB - We have investigated the expression of class II major histocompatibility complex (MHC) antigens in human renal allografts before, during, and after the first episode(s) of rejection, and correlated the antigen expression with the cytological pattern of inflammation as well as with the extent of steroid administration. The results confirm that the class II MHC antigens are rapidly lost from a renal transplant after successful transplantation. Downregulation of graft class II antigenicity was observed in all three immunosuppressive regimens employed, with a steroid dose ranging from 0.5 +/- 0.2 mg/kg/day to 1.8 +/- 0.3 mg/kg/day of methylprednisolone. During rejection the class II MHC antigens reappear in the graft parenchymal (vascular endothelial and tubular) cells, whereas after the successfully treated episode they again disappear from the graft. The upregulation of graft antigenicity is associated only with inflammatory patterns with a distinct blastogenic component; nonblastogenic patterns of inflammation are not associated with upregulation of class II antigens. During blastogenic inflammation, the extent of class II antigen expression was inversely proportional to the amount of steroid administered. The results support the suggestion that upregulation of class II antigen contents in a graft is due to (gamma-interferon released by) the inflammatory (T) blast cells, and suggest that a major downregulating mechanism of class II antigen expression is administration of glucocorticosteroids. PMID- 3094210 TI - Immunological characteristics of purified pancreatic islet grafts. AB - In a DBA/2 (H-2d) pancreatic islet-to-B6AF1 (H-2b/k.d) recipient combination, the graft survival of hand-picked islets was compared with that of "crude digested" islets that were prepared simply by collagenase digestion and Ficoll gradient separation and were contaminated with lymph nodes and vascular and ductal tissue. Islet allografts were transplanted into the renal subcapsular space of streptozotocin-induced diabetic recipients. No immunosuppression was used. All the crude digested islet allografts were acutely rejected between days 7 and 18 with a median survival time (MST) of 10.2 +/- 2.5 days. In contrast, 33% (3/9) of the purified islet allografts survived more than 100 days. Simultaneous transplantation of purified islets and contaminating tissue resulted in a shorter graft survival (MST of 15.6 +/- 3.7 days). When 5 X 10(7) donor strain spleen cells were injected i.v. at the time of transplantation, all purified islet grafts were acutely rejected within 9 days. In addition, the rejection time of the purified islet allografts was inversely correlated with the number of donor spleen cells injected. These results indicate that contaminating tissues such as lymph nodes, vascular tissue, and ductal fragments present in the crude digested islet allografts are a major stimulus for induction of an immune response resulting in acute rejection of islet allografts. PMID- 3094209 TI - Functional assessment of T cell depletion from bone marrow prior to therapeutic transplantation using limiting dilution culture methods. AB - We evaluate the usefulness of limiting dilution culture methods in assessing the extent of T lymphocyte depletion from bone marrow inocula, prior to transplant, using either ex vivo antibody/complement-mediated depletion or immunotoxin treatment. Complement-mediated depletion using anti-Leu-1 antibody was shown to result in a consistent decline of 99%-99.9% in the frequencies of T cells able to proliferate in mitogen-stimulated, interleukin-2 (IL-2)-supplemented cultures. Equivalent declines were demonstrated in frequencies of "helper" T cells able to respond to mitogen by making IL-2, and in "killer" T cells able to give rise to clones of cytotoxic effectors. In most experiments, a second cycle of anti-Leu-1 + complement treatment did not further diminish the fraction of proliferating cells, although T cells able to secrete IL-2 were additionally depleted following a second cycle of antibody and complement. The limiting dilution methods were found to be at least as sensitive as flow cytometric (FACS) methods for detecting residual T cell contamination after protocols involving complement-mediated lysis, and superior to FACS analysis for protocols involving T cell depletion by a ricin A chain-anti-T101 immunotoxin, in which treated T cells suffer functional impairment and eventual death after exposure to immunotoxin, but remain phenotypically detectable during FACS analysis. Although limiting dilution methods do not provide data as rapidly as FACS analyses, they do not require a cytofluorimeter, provide equal or greater sensitivity, and can assess functional impairment, for both helper and killer T cell sets, even in situations in which the depletion procedure does not lead to immediate cytolysis. PMID- 3094211 TI - Canine islet cell transplantation under the kidney capsule. PMID- 3094212 TI - Feeding patterns of children with protein-energy malnutrition in Nigeria. PMID- 3094213 TI - [The origin of the eukaryotic cell. II. A critical analysis of the symbiotic (exogenous) concept]. AB - The exogenous (symbiotic) conception of the eukaryotic cell origin is unable to explain satisfactory the structure of mitochondria and chloroplasts. Either of these organelles possess its genome that can be compared with the viral one rather than with the bacterial one, judging by the dimensions and quantity of coding genes. The mitochondria resemble a little prokaryotes in the number of their proteins, chemical composition of their inner membrane and peculiarities of the protein-synthesizing apparatus. The primitive structure of mt DNA, the lesser quantity and greater unspecifity of the mitochondrial tRNA prove, additionally, the non-bacterial origin of this organelles. The deflexion of the genetic code from the universal one in the mitochondrial nucleoids also testify in favour of this point of view. The results of micropaleontological and paleobiochemical investigations evidence towards initial ability of the primary eukaryotes (primary protists) to photosynthesis. In this case, they did not need to acquire plastids from outside by symbiotic way. The autogenous origin of the flagellum of the primary protists was reported earlier (Seravin, 1985). The accumulated data permit us to consider that the cell organelles formed endogenously in the process of evolution of the cell. PMID- 3094214 TI - Theileria infectivity of Hyalomma ticks in Haryana, India. AB - Theileria infection of Hyalomma ticks collected from three districts of Haryana was assessed in whole salivary glands by the methyl-green pyronin staining method. Of 1,662 ticks screened, 546 (32.8%) were found Theileria positive. Infection rate in 935 female ticks (36.9%) was more than that of 727 male ticks (27.6%). Density of Theileria infection (number of infected acini per infected tick) was also higher in female ticks. Theileria infection rate of ticks varied greatly in the three districts viz. only 12.0% in Rohtak, 25.8% in Hisar and 48.3% in Karnal. Per cent infection rate was high (63.7%) in ticks from indigenous cattle and low (18.6%) in those collected from buffaloes. However, the intensity of infection in infected ticks from cross-bred cattle was comparatively much higher. Frequency distribution of Theileria positive acini in infected ticks revealed a low density of infection per infected tick. This points to the largely stable endemic situation prevailing in Haryana. Only a single salivary acinus was found infected in 16.6% of the infected ticks, about 70% had up to 10 infected acini while only about 10% had over 25 infected acini per tick. The masses in acini presumed to be Theileria were confirmed by demonstrating parasitic masses on staining one of a pair of salivary glands and inoculating the suspension of the other half of the gland into two cross-bred cow calves which developed clinical signs and lesions typical of theileriosis. PMID- 3094215 TI - Prolactin response to thyrotropin-releasing hormone in early and advanced human breast cancer. AB - While prolactin (PRL) has been shown to stimulate the development of mammary carcinoma in several animal species, its role in human breast cancer remains to be established. To further investigate PRL secretion in human breast cancer, its basal levels and response to thyrotropin-releasing hormone (TRH) were evaluated in 16 patients (6 with no metastases and 10 with metastatic locations). The control group consisted of 19 healthy women. High PRL basal concentrations were seen in 2 patients only; no significant differences were found between the other patients and the normal subjects. The PRL increase induced by TRH administration was significantly higher in patients than in controls. Finally a change in the hormonal secretion was found after chemotherapy in 3 of the 5 patients in whom PRL response to TRH was evaluated either before or 10-12 days after a cycle of intravenous CMF adjuvant chemotherapy. These results demonstrate the existence of an exaggerated response of PRL to TRH in patients with breast cancer, even in the presence of normal basal levels. Moreover, they would seem to suggest a possible influence of CMF on PRL response to TRH stimulation. PMID- 3094216 TI - Cost-effectiveness of chest X-ray follow-up of patients treated for seminoma of the testis. AB - The authors report on a consecutive series of 253 cases of seminoma of the testis followed with periodic chest X-ray examinations from a minimum of three to a maximum of 27 years. The detection rate of asymptomatic intrathoracic metastases (ITM) was considered together with the costs of the follow-up procedure. Chest X ray follow-up is not advisable beyond one year from primary treatment, since most (14 of 18) ITM occur in the first year, the detection rate of ITM beyond this date is too low (0.11% patients/year), and the related costs are too high (over $130,000 per ITM detected). Chest X-ray follow-up is questionable even in the first year after primary treatment for Stage I cases because of the low detection rate (1.38% patients/year) and the high costs (over $14,000 per ITM detected), whereas it appears to be opportune in Stages IIA and IIB. PMID- 3094217 TI - [Bladder diverticulum at an atypical site]. AB - An atypically located diverticulum of the bladder was found in five anatomical dissection specimens. The diverticulum with a depth of about 1-3 cm developed in the bladder's lateral wall. The diverticulum seems to be caused by a strong fibrous cord originating from the bladder's wall and penetrating the canalis obturatorius. Within the channel the cord is anchored by a voluminous fat body. Histologically the wall of the diverticulum reveals typical signs of chronic inflammation. PMID- 3094218 TI - Neurofibromatosis, factor IX deficiency, and rhabdomyosarcoma. AB - A paratesticular rhabdomyosarcoma occurred in a child with factor IX deficiency and neurofibromatosis, illustrating the need to consider carefully the various etiologic possibilities of a soft-tissue mass in a child with neurofibromatosis and/or a bleeding disorder. PMID- 3094219 TI - Role of urodynamics in management of urethral diverticulum in females. AB - This report deals with 10 female patients with urethral diverticula, 8 of whom were also found to have findings of stress incontinence. This association was proved by urodynamic studies. Three patients were seen with incontinence postdiverticulectomy. Seven patients were evaluated prior to diverticulectomy, and of these 5 had anatomic changes of stress urinary incontinence. Those patients in whom the preoperative evaluation considered them to be at risk for development of stress incontinence postdiverticulectomy were treated with a prophylactic urethropexy. Patients so treated were continent and voided well and were probably spared having a postoperative problem with incontinence. The role of urodynamic techniques in the detection of any association between the diverticulum and a possible risk of postdiverticulectomy incontinence, and how to recognize the problem and its correction before it becomes clinically manifest are the stated purposes of this report. PMID- 3094220 TI - [Detection of antibodies to mycoplasmas using an immunoenzyme method]. AB - Detection of the antibodies to the species Mycoplasma bovis in the serum and milk of dairy cows coming from a mastitis-infected herd is a good example of utilization of the ELISA immunoenzymologic method in the mycoplasmology. Examining the samples from 75 dairy cows and applying the indirect hemagglutination test, good correlation of the results of the two tests was determined. The antibodies to the species Ureaplasma diversum were demonstrated by the ELISA method both in the bovine serum and in the milk of dairy cows infected slightly with mastitis. We chosen that strain which detected the maximum titres in the selected samples of the sera out of four antigens prepared from various strains of U. diversum. Rabbit sera hyperimmune to 26 strains of the mycoplasmas of various species were used to identify two antigens (after removing the antibodies to the components of the media). Specific reaction was obtained with the antisera to M. hyorhinis and M. arginini. PMID- 3094221 TI - [Immunoenzyme (ELISA) diagnosis of spring viremia in carp]. AB - The enzymoimmunologic (ELISA) method was used to diagnose spring viremia in carp. The specific antibodies to Rhabdovirus carpio in the fish sera were detected by this method. Reaction specificity was tested by the use of viral and control antigens, by examination of positive and negative sera and by serum-free control incubation. Applying the ELISA method, the antiviral antibodies can be detected after infection or vaccination: this method is therefore suitable for thorough studies and when choosing the appropriate treatments and preventive measures. PMID- 3094222 TI - [A decrease in blood beta-carotene in dairy cows during late pregnancy period]. AB - In four successive seasons of green and winter feeding in the years 1980-1984, beta-carotene concentrations were determined in the plasma of venous blood of 3441 cows in the first phase of lactation, in the other phase of lactation, in the eighth month of pregnancy and in the 9th-9.5th months of pregnancy. The cows in the other phase of lactation had the significantly highest beta-carotene concentrations in the two feeding seasons. In the eighth month of pregnancy there occurs a significant drop that continues also in the 9th-9.5th months of pregnancy. In the first phase of lactation beta-carotene concentrations remained at the level of the values from the 9th-9.5th months of pregnancy. In the period of winter feeding, the mean concentrations of beta-carotene in all groups of cows were deep below the limit value of 7.44 mumol . l-1, which indicated that it was necessary to fortify feeds with vitamin A; in the cows in the 9th-9.5th months of pregnancy and in the cows in the first phase of lactation they were lower than the critical value of 5.58 mumol.l-1, which signaled the disorders of reproduction processes. In the course of the years of investigation beta-carotene concentrations varied in the same manner in all groups of cows in keeping with the vegetation period of the feed, feed kind and quality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094223 TI - [The extent of the incidence of sarcocystosis in cattle and pig farms]. AB - The extensity of a chronic form of sarcocystosis was studied in certain age categories of cattle and pigs. The incidence of sarcocysts was investigated microscopically after 0.25% trypsin action in the muscles of bovine gullet and diaphragmal columns of pigs. Bovine fetuses and sucking calves did not have any sarcocysts. The first cases of positive findings were recorded in calves on milk diet (18.33%). The infestation rate of adult cattle is high in this country and reaches the level of 90%. The disease extensity in pigs is lower by an order and it did not exceed the level of 4%. There were found no significant differences (the mean 81.85%) in the infection rate in the cows coming from various regions of the CSR if the incidence of the disease was evaluated geographically. Larger percent differences were recorded between cattle and pig herds, mostly in the South Moravian Region, if evaluated by the districts and farms. The results of the investigation of 1273 head of cattle and 335 head of pigs coming from various farms were processed statistically. We tested the sarcocyst incidence in the muscular tissue in relation to the ways of housing and seasonal changes. Considerably lower rates of sarcocystosis infestation on the large cattle and pig farms were demonstrated. In the other case no relationship was proved. The samples taken in all year seasons could be evaluated in the same objective way. We discuss potential preventive measures of this parasitosis-zoonosis. PMID- 3094224 TI - [The clinical course and differential diagnosis of papular dermatitis in fattened pigs]. AB - Since December 1981, dermatitis of unknown etiology in form of papular lesions has appeared in fattened pigs in some large herds in the Czech Socialist Republic. Clinical investigations of diseased pigs were performed in a large fattening house D. and in a large production herd of pigs M. in the region with frequent mines (lignite extraction). The diameter of the papules is mostly 3-5 mm, they are not painful when touched, are straggled irregularly, their large numbers are on the upper surface of the body. Papular dermatitis has a chronic course, affecting the gilts and castrated boars from the body weight of 30 kg, irrespective of their nutritional status. The overall health condition of pigs is not impaired and the disease does not cause itch. In the infected herds, there are usually fewer than 30% of pigs suffering from the disease. The incidence of the disease is highest in winter months. It is necessary to distinguish by differential diagnostics: swine pox, parakeratosis of swine, lesions of impetigo contagiosa suum, pustular dermatitis and scab of swine, from rarely occurring skin diseases of swine hypotrichosis cystica suis and demodicosis of swine. Neither did preventive nor therapeutic measures reduce expressively the incidence of skin lesions. We hope that the complex investigation of the internal environment of the infected pigs could help to reveal the pigs sensitive to the infection by this disease. PMID- 3094225 TI - [Use of a fixation device and hematocrit capillaries for the collection of blood in wild birds for virologico-serologic examination]. AB - There is a description of the fixation and blood sampling in small birds by means of hematocrit capillaries. The volume of 25-30 microliters serum can be taken safely from a 75 cm long capillary filled with blood. This amount is large enough for examination by the micromethod of hemagglutination-inhibition test (HIT) and component-fixation reaction (KFR). Even potentially infectious material can be centrifuged in a capillary sealed at both ends. The procedure is suitable to be used for repeated samplings during long-term experiments or for biochemical examinations of small birds kept in cages. PMID- 3094226 TI - [Numerical calculation of basic indicators of blood acid-base balance using an equilibration method]. AB - There is a description of an algorithm of the numerical calculation of the values of actual partial pressure of CO2, actual bicarbonates, standard bicarbonates, base excess (BE), concentration of buffer bases (BB) and hemoglobin when the equilibration method of determining the acid-base balances of blood after Astrup is used. We applied the equations of the simulating curve of Siggard-Anderson nomogram to the calculations of BB and BE. PMID- 3094227 TI - [The complex etiology of epidemic diseases in calves on large-capacity farms and their clinical and epizootic characteristics]. AB - It is not easy to exactly diagnose the etiology of the mass infections of new born calves on large farms where considerable losses are suffered. On the basis of the complex epizootological, clinical and laboratory examination in four large calf-rearing facilities, rotaviruses, coronaviruses, the infectious bovine rhinotracheitis (IBR) virus and the bovine viral diarrhoea (BVD) virus, and in some cases also the enteropathogenic E. coli, were found to be etiologically involved in the mass rise of diarrhoea, complicated by respiratory symptoms already during the first days after birth. The clinical picture of the disease, therapeutically difficult and reminding of "pneumoenteritis", has often been observed in stocks where, in addition to rotaviruses and coronaviruses in the faeces, the IBR or BVD viruses (sometimes both at the same time) were detected and identified in the respiratory and enteral tract. The serological examination of a higher number of animals in the stocks of calves under study confirmed the considerable rate of spreading of all the four viruses in the cattle population and, at the same time, demonstrated the very unfavourable immunological profile of the herds. The high percentage of animals low in antibody titres and the serologically negative animals constitute the infection-sensitive part of population in the affected herds. With the high culling rate and with the open herd turnover it is impossible to reach the required immunity through natural disinfection. Loss-free rearing of healthy calves will be achieved on the basis of a well-oriented vaccination programme with a good combination of inoculants. PMID- 3094228 TI - Conservation among the immunoglobulins of carcharhine sharks and phylogenetic conservation of variable region determinants. AB - To study primitive vertebrate recognition molecules we have purified the immunoglobulins of three species of carcharhine sharks. The tiger (Galeocerdo cuvieri), the sandbar (Carcharhinus plumbeus) and the galapagos sharks (Carcharhinus galapagensis) possess 18S high molecular weight and 7S low molecular weight immunoglobulin forms. Both within and between species these forms closely resemble each other in polypeptide chain composition, heavy chain mass, carbohydrate content, amino acid composition, antigenic character and amino terminal sequence. These carcharhine species are separated by at least 30 million years of evolutionary time and it is remarkable that so little diversification of immunoglobulin structure has occurred during their evolution. By several criteria carcharhine immunoglobulins most closely resemble mammalian IgM. Studies of serological cross-reactions indicate that some immunoglobulin determinants have been conserved over a broad phylogenetic range of vertebrate classes; most notably JH and VHa-related markers are shared between forms as diverse as sharks and mammals. PMID- 3094229 TI - Putative immunoglobulin VH genes of the goldfish, Carassius auratus, detected by heterologous cross-hybridization with a murine VH probe. AB - By using a defined cDNA probe for the VH region of a murine phosphocholine binding myeloma protein (S107) we have defined a family of distinct cross hybridizing DNA sequences in genomic DNA of the goldfish. The estimated number of the goldfish putative VH family detectable by the S107 probe is about 36. By using two putative goldfish VH probes to analyze, by hybridization, the relationships among seven of the goldfish genomic clones, we have determined that the putative goldfish VH genes recognized by the S107 probe comprise at least several distinct families that are not closely related. PMID- 3094230 TI - Paradoxical effects of cadmium exposure on antibacterial antibody responses in two fish species: inhibition in cunners (Tautogolabrus adspersus) and enhancement in striped bass (Morone saxatilis). AB - Previous work in a marine fish, the cunner (Tautogolabrus adspersus), showed that endocytosis of bacteria by cells in the liver and spleen was affected by 96-h exposure of the fish to cadmium at a concentration of 12 micrograms/ml; however, antibody response to sheep erythrocytes was not affected. Since the latter finding was questionable because of short immunization times, and data from more than a single fish species were desirable, both the cunner and an anadromous fish, the striped bass (Morone saxatilis), were examined for antibody responses against the bacterium Bacillus cereus in Freund's complete adjuvant during a 6- to 8-wk time period. Exposure to 12 micrograms/ml cadmium caused significant inhibition of serum antibody titers (P less than 0.007) in cunners. Paradoxically, antibody response in striped bass exposed to 10 micrograms/ml cadmium was enhanced sixfold. This enhancement was weaker but still evident when the antigen was injected 48 d after cadmium exposure. Peritoneal exudate cells from cadmium-exposed striped bass also showed more active migration through microporous filters than cells from non-exposed fish. Since the 96-h cadmium LC50 was 26 micrograms/ml for cunners and 20 micrograms/ml for striped bass, the differences in antibody response could not be explained on the basis of differences in cadmium toxicity. Although geometric mean liver cadmium levels after exposure at 15 degrees C were higher in cunners (163.8 +/- 1.2 micrograms/gm) than in striped bass (64.4 +/- 1.2 micrograms/g), cunners exposed to cadmium at 2 degrees C had lower cadmium levels (46.4 +/- 1.2 micrograms/g) which were still effective in inhibiting antibody production at 8 degrees C. On the other hand, striped bass not exposed to cadmium showed a strong, exponential rise in serum antibody when the temperature at immunization, 14 degrees C, was reduced to 9 degrees C; whereas cunners held in the same tanks exhibited a weaker, biphasic serum antibody response. Regardless of the cause (innate differences in cellular response, or better stress adaptability in an anadromous fish), the data show that chemical-stress effects on the immune system of one fish species cannot be extrapolated to another species. PMID- 3094231 TI - The seasonal antibody response in juvenile summer flounder (Paralichthys dentatus) to the hemoflagellate Trypanoplasma bullocki. AB - An immuno-blot assay was used to investigate the serum antibody response in flounder injected with formalin-killed flagellates (immunized) and those injected with saline (control) and challenged with live T. bullocki after 21 days. Fish were held at 20 degrees C and at ambient temperature from October through June. At 20 degrees C immunized fish had significantly higher antibody titers than control fish, but immunized fish were not protected from infection with T. bullocki. At ambient temperature, after initial flagellate growth phase, antibody titer varied directly with temperature (2-25 degrees C) and T. bullocki intensity varied inversely with titer. Flagellates were eliminated from the peripheral circulation in both immunized and control fish when antibody titer peaked in May. Recovered fish were immune to homologous challenge for at least one year. PMID- 3094232 TI - The immune response of a marine teleost, Pseudopleuronectes americanus, (winter flounder) to the protozoan parasite Glugea stephani. AB - G. stephani is an intracellular cyst-forming microsporidan parasite that is found in the intestine of winter flounder (WF) Pseudopleuronectes americanus. No detectable humoral response was seen in parasitized fish or in fish injected with either spores or spore homogenate from this parasite. Quantification of total immunoglobulin (Ig) levels showed a decrease in Ig levels rather than enhancement, 21 days after intramuscular (IM) injections of spores (3 X 10(6)/ml). When a second injection of spores was administered on day 21 and tested 3 weeks later, a further decrease in total serum Ig's occurred. A decrease in total IgM levels also occurred in WF that were simultaneously injected with G. stephani and the antigens, horse red blood cells (HRBC) or formalin-killed Klebsiella pneumonia (KP). The total Ig levels of fish injected with an antigen plus spores was not as low as those injected with the parasite alone. The Ig levels, as well as antibody titers to HRBC and KP were however, lower when compared to fish injected only with the HRBC or bacteria. Disrupted spore homogenate injected into winter flounder, showed a less marked decrease in Ig levels when compared with whole spores. When a single IM injection of spores was given, followed by two weekly injections of indomethacin (a drug that inhibits prostaglandin activity), no decrease in Ig levels occurred and levels were comparable to control (saline injected) fish. PMID- 3094233 TI - Immunosuppression of carp (Cyprinus carpio L.) to ichthyophthiriasis using the corticosteroid triamcinolone acetonide. AB - The immune response of juvenile mirror carp (Cyprinus carpio L.) has been investigated in relation to protective immunity and immunosuppression to the disease ichthyophthiriasis. Protective immunity was induced by exposing juvenile carp to approximately 2,000 theronts per fish for 3 hours at a concentration of approximately 80 theronts cm-3 in dechlorinated water pH 7.0-7.2, 20 +/- 2 degrees C in the dark, on three separate occasions of 14 day intervals. Following each exposure, re-infection was prevented by transferring fish to clean aquaria twice daily from day 5-10. Fish were challenged 4 weeks following exposure to the third immunising infection with a potentially lethal dose of approximately 8,000 theronts per fish for 3 hours at a concentration of approximately 320 theronts cm 3. All immunised fish survived although 19% showed initial signs of invasion, the parasites in these instances being confined to periphery of fins. Mortalities of 100% were recorded in non-immunised controls, first deaths occurring 5 days after challenge. Fourteen days following challenge, immune fish received one of the following treatments; intraperitoneal injection of the corticosteroid triamcinolone acetonide at a dose of 200 micrograms g-1 body weight, intraperitoneal injection of 0.85% saline or left untreated; non-immunised fish were subjected to similar procedures. On challenge 6 days later, all fish developed heavy infection with up to 100% mortalities with the exception of immunised fish administered saline or left untreated. Repeat experiments gave comparable results. The results indicate that immunosuppression can be induced by administration of high levels of synthetic corticosteroid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094234 TI - Structural diversity of channel catfish immunoglobulins. AB - This paper describes a number of observations which show that the covalent structure of catfish Ig is heterogeneous and secondly that different Ig L chain classes are present. PMID- 3094235 TI - Preparation of anti-bovine and porcine mu chain sera. AB - Absorption of anti-L chain antibodies contained in anti-IgM sera immunized with purified bovine and porcine IgM was undertaken by affinity chromatography on a column of Sepharose 4B, coupled with the normal follicular fluids of the respective species as an immunosorbent. Anti-L chain antibodies in both anti-IgM sera were completely absorbed without incurring reduction of the antibody titer, and anti-bovine and anti-porcine mu chain sera were prepared. PMID- 3094236 TI - IgG precipitating and non-precipitating antibodies in rabbits repeatedly injected with soluble and particulate antigens. AB - The immune response of precipitating antibodies and non-precipitating antibodies of high affinity (co-precipitating) of the IgG class was analyzed in rabbits repeatedly injected with egg albumin (as a soluble antigen) B. abortus-egg albumin and polymerized egg albumin (as particulate antigens). The results showed that the levels of anti-egg albumin non-precipitating antibodies induced by the soluble antigen were never higher than 10-15% of total antibodies throughout the experimental time. When particulate antigens were injected, the levels of non precipitating antibodies increased up to 30-70% of the total antibody levels. This phenomenon is related to the way in which the antigen is available to the immune system (particle or aggregated), and is independent of the response induced by the particulate carrier. Components from the cell wall or bacterial membrane that could act as coadjuvants do not participate in this phenomenon. The results obtained seem to indicate that possibly there was a suppression of the synthesis of precipitating antibodies, and this would produce a relative increase in the non-precipitating antibodies. PMID- 3094237 TI - Immunomodulation with killed Propionibacterium acnes in guinea pigs simultaneously vaccinated with Brucella abortus strain 19. AB - Immunomodulation with killed Propionibacterium acnes was attempted in guinea pigs simultaneously vaccinated with Brucella abortus strain 19. Two groups, each comprised of 9 guinea pigs, were injected by different routes (s.c. and or i.v.) with 1.4 mg of P. acnes and 5 X 10(8) CFU of B. abortus, S-19, while 3 other groups each received either P. acnes, B. abortus S-19, or saline (s.c.). The antibody titers to B. abortus measured at 6, 10 and 14 weeks after vaccination indicated no significant (P less than 0.01) response in the 2 groups immunopotentiated with P. acnes concurrent with B. abortus S-19 vaccination. The delayed hypersensitivity response to 3 Brucella antigens conducted 8 weeks after immunization did not show a significant difference between the B. abortus S-19 vaccinated group compared with the 2 groups immunopotentiated and vaccinated. However, the proliferative response of lymphocytes to the B. abortus soluble antigen diluted 1:100 indicated significantly enhanced blastogenesis in the (s.c.) immunopotentiated and immunized guinea pigs compared with the B. abortus S 19 vaccinated group. A slightly enhanced response was also observed in the group immunopotentiated (i.v.) and vaccinated (s.c.). The guinea pigs were challenged with B. abortus strain 2308 and necropsied 4 weeks later. The mean splenic CFU of the Brucella in the group immunopotentiated (i.v.) and vaccinated (s.c.) was significantly decreased when compared with the guinea pigs vaccinated with B. abortus S-19 alone. These findings indicated that P. acnes administered simultaneously with B. abortus S-19 vaccine was able to augment the immune response in guinea pigs. Immunomodulation as evidenced by enhanced clearance of B. abortus from the spleens of immunopotentiated animals was presumably brought about by activated macrophages or a T-cell mediated cytolytic mechanism or both. PMID- 3094238 TI - In honour of Gerhard Seifert on the occasion of his 65th birthday. PMID- 3094239 TI - Intermediate-filament expression in thyroid gland carcinomas. AB - Paraffin-embedded specimens of 200 primary thyroid carcinomas were examined immunohistologically for the expression of intermediate-filament (IF) protein of the cytokeratin, vimentin and neurofilament type. In 36 cases, snap-frozen tissue was available, and double label immunofluorescence microscopy was performed in 23 of them. Cytokeratin reactivity was found in all cells of all follicular, papillary and medullary carcinoma cases examined. Using a monoclonal vimentin antibody, positive staining was found in many, though not all cells of the papillary tumours and in approximately 50% of the follicular and the medullary carcinomas. Among anaplastic carcinomas, some tumours were positive for cytokeratins, with or without coexpression of vimentin. Neurofilaments could only be demonstrated in approximately 13% of medullary tumours which in general also exhibited vimentin positivity. The differences of IF expression in follicle and C cell thyroid carcinomas and the broad variation of cytokeratin and vimentin immunoreactivity among anaplastic tumours of this organ is discussed in relation to the possible intrinsic heterogeneity of these tumours and the diagnostic value of these markers. PMID- 3094240 TI - Bone metastases of differentiated and medullary thyroid gland carcinomas. Usefulness and limitations of immunohistology performed on undecalcified plastic embedded tissue specimens. AB - Undecalcified methylmethacrylate(MMA)-embedded biopsies and surgical specimens from 20 bone metastases of differentiated or medullary thyroid carcinomas or prostate carcinomas were investigated immunohistologically for the presence of thyroglobulin, cytokeratin, vimentin, and CEA. The immunoreactions on MMA sections revealed the same staining patterns as those demonstrated using paraffin sections of the primary lesions. Conversely, immunohistological examination of decalcified paraffin-embedded specimens of the same metastases yielded either false-negative results or results that did not allow an exact evaluation. The findings demonstrate the usefulness and limitations of immunohistology when performed on undecalcified plastic-embedded material. PMID- 3094241 TI - Human acute pancreatitis: its pathogenesis in the light of immunocytochemical and ultrastructural findings in acinar cells. AB - Human acute pancreatitis results from an autodigestive process frequently associated with alcohol abuse, gall stone disease and shock. Peripancreatic fat necrosis was identified as one of the earliest visible lesions, whereas acinar cell necrosis and haemorrhage were regarded as secondary changes. To examine the alterations in acinar cells in more detail, their enzyme content and fine structural features were studied immunocytochemically using antisera against alpha-amylase, lipase, trypsin, chymotrypsin and pancreatic stone protein, and electronmicroscopically in pancreatic tissues from patients with severe acute pancreatitis. Peripheral acinar cells in the immediate vicinity of fat necrosis were found to be heavily degranulated, while acinar cells at some distance of necrosis fully retained their enzyme content. Other frequent changes of the acinar cells included cuboidal transformation, loss of microvilli, increased occurrence of autophagosomes, and formation of enlarged acinar lumina. As there was no apparent cell membrane leakage or rupture of duct lumina, it is concluded that the acinar cells adjacent to fat necrosis release their granules by undirected basolateral extrusion. The findings thus suggest that one of the basic defects in acute pancreatitis is the uncontrolled release of enzymes from peripheral acinar cells into the interstitial space which, in turn, presumably by the action of lipase, leads to autodigestive fat necrosis. PMID- 3094242 TI - Histomorphometric analysis of osteoclastic bone resorption in metastatic bone disease from various primary malignomas. AB - The present study deals with qualitative und quantitative analysis of osteoclastic bone resorption in metastatic bone disease. 267 cases were examined histomorphologically and divided into three developmental stages. In the first 'phase of early appearance' no bone resorption takes place. The stimulation of osteoclastic resorption in the surroundings of tumour tissue is typical in the second 'phase of interaction'. Pressure atrophy, aseptic necrosis and osteolysis by the tumour cells themselves are other mechanisms of bone destruction in the last 'phase of carcinomatosis'. Because osteoclasts are exclusively responsible for the loss of bone tissue in the 'phase of interaction', this stage is suited for precise quantitative analysis of osteoclastic resorption. 24 pure osteolytic secondary bone tumours of various primary lesions were examined histomorphometrically. The numerical values were compared with each other and with standard values of healthy individuals. In contrast with normal bone tissue the fractional resorption surfaces und osteoclast indices increase in metastases. Activated osteoclasts are larger and have more nuclei. The numbers of osteoclast index and nuclei per osteoclast are significantly higher in renal than in breast carcinoma. Osteoclasts can be activated in distances of more than 500 micron from tumour tissue. The mean stimulation distance in metastasis from squamous cell carcinoma is markedly higher than in secondary bone tumours of breast carcinoma. Several osteoclast activating substances and divers mechanisms of stimulation might be responsible for different numerical values of morphometric parameters in metastases from various primary malignancies. PMID- 3094244 TI - Utilization of short-stay hospitals by diagnosis-related groups. United States, 1980-84. PMID- 3094243 TI - Nuclear DNA content of borderline tumors of the ovary: correlation with histology and significance for prognosis. AB - Scanning-DNA cytophotometry was applied to Feulgen stained sections of 22 borderline tumors of the ovary (BOT). The DNA content was related to conventional histology. In 11 cases clinical follow up for more than 5 years was available. The DNA measurements disclosed two subgroups in the group of BOT. One showed a nuclear DNA content not exceeding tetraploidy (4c) indicating proliferative activity without malignant change and a second one exhibited DNA values higher than 4c indicating malignant transformation. Correlation of histological evaluation with the DNA content revealed a good agreement in 15 cases. However, a discrepancy was found in 7 cases: either the histological evaluation aroused suspicion for malignant potential but the histogram showed DNA values not higher than 4c (n = 4), or histology showed well differentiated lesions with an atypical histogram (n = 3). Clinical monitoring revealed no recurrence or tumor spread in all but one case of the group of lesions with DNA values up to 4c, whereas in the group with atypical DNA histograms (DNA values greater than 4c) relapse appeared in 6 out of 7 cases. The results suggest that DNA analysis has prognostic significance for BOT. PMID- 3094245 TI - [The effect of nitroglycerin on polygraphic indicators of cardiac dynamics in patients after myocardial infarct]. PMID- 3094246 TI - [The 4th heart sound and values of diastolic indicators in the apexcardiogram in patients after myocardial infarct. The effect of nitroglycerin]. PMID- 3094247 TI - [The rate of elimination of homologous and heterologous native and modified high density lipoproteins from rabbit plasma after their intravenous administration]. AB - Rates of catabolism of total fraction of human native high density lipoproteins (HDL) and their subfractions as well as horse and rabbit native and modified HDL were studied after intravenous administration of the HDL into healthy rabbits and the animals with experimental hypercholesterolemia. The following procedures were carried out for production of HDL derivatives: methylation, succination, blocking of Arg residues and of COOH-groups. Rates of catabolism were similar for rabbit and horse total fractions of 125I-HDL, whereas human HDL were catabolized at a slightly higher rates as compared with rabbit lipoproteins. After administration of human total HDL fractions their elimination, estimated by output of alpha cholesterol (alpha-C), occurred at a higher rate in healthy rabbits as compared with the animals with hypercholesterolemia, whereas output of apoprotein (apo) A I was similar in both these groups. As HDL are able to exhibit the properties of alpha-C donor in circulation, estimation of apo A-I should be a more reliable index of the HDL content in blood plasma as compared with alpha-C. Chemical derivatives of rabbit HDL were eliminated from circulation of control animals at a rate similar to that of native HDL rate, but exceeding the rate established for succinated HDL. As compared with native HDL all the modified horse HDL were eliminated at the higher rate from the circulation of healthy rabbits. In rabbits with hypercholesterolemia the higher rate of elimination was shown only for succinated and methylated HDL fractions. Succinated HDL were catabolized at the highest rate apparently due to marked negative charge of their molecules. The data obtained suggest that in rabbits HDL are catabolized via pathways which do not involve specific cell receptors. PMID- 3094248 TI - [Content of mineral substances in the internal organs of rats on intravenous feeding]. AB - The experiments on rats receiving a complete intravenous nutrition (group 1) during 15 days showed that the concentration of natrium, magnesium and iron was increased in the liver and decreased in the spleen as compared to that in controls given normal feeding (group 2). The content of zink and copper (mg%) was significantly lowered in both the organs of rats in group 1. The growth of the liver and spleen mass during parenteral feeding led to a significant rise in the content of natrium, potassium, magnesium, iron, zink and manganese in the whole liver tissue of group 1 rats, while the content of calcium and copper was similar in both groups of animals. The content of natrium, potassium, magnesium, iron and zink in the whole spleen tissue was significantly higher in group 1 rats, while the content of calcium, copper and manganese was similar in both groups of rats. A correlation was revealed between the content of iron and copper in the liver tissue (r = +0.87) and the levels of natrium and magnesium it the spleen tissue (r = +0.78) of group 1 rats. In group 2 rats a correlation was recorded between the content of calcium and manganese in the liver tissue an the levels of natrium and calcium in the spleen (r = +0.85 and +0.86, respectively). PMID- 3094249 TI - Recognition and management of immunodeficient disorders. Introduction. PMID- 3094250 TI - Immunologic disorders: the regulation of humoral immunity. AB - The modulation of humoral immunity by complement and complement receptors is presented, as well as the importance of the X chromosome in immune response. Gene rearrangement and ontogeny of the immunoglobulin isotypes are discussed with regard to humoral immunodeficiency diseases. PMID- 3094252 TI - [Treatment of acute viral hepatitis with cortisone]. AB - The indications for cortisone administration as well as of its derivatives in the treatment of viral hepatitis (VH) have been discussed on the base of personal experience and literature data. It has been concluded that cortisone has lost its role in the treatment of VH because of its numerous negative effects, recurrences, steroid diabetes, ulcers, hemorrhages, liability to infections, and most important--the liability to chronification and long-term carriership in VHB. Manifested intoxication phenomena and impeding and present endogenic hepatic coma, remain for the present, the main indications for cortisone treatment in VH. In VHA and VH non A--non B it is not necessary and in VHB it could even by admitted to be contraindicated due to the risk of chronification and long-term carriership. It has been emphasized that post-transfusion hepatitis are with the severest course, responsible for the lethality, hence the main treatment in them remains the prophylaxis with passive and active immunization. PMID- 3094251 TI - Recognition and treatment of immune disorders at the time of birth. AB - Neonatal immunology offers a fertile field for the investigator. Not only does it supply a great deal of information about immunology in general, but it also presents challenges peculiar to this critical period of life. The complement, phagocytic, antibody, and T cell systems in the neonate have characteristic defects and inadequacies. The genetic conditions that compromise the newborn's immune system are discussed in terms of clinical manifestations as well as laboratory abnormalities. In addition, patterns that may suggest the presence of immunodeficiency are described. Finally, methods of managing the immunodeficient infant are outlined, including clinical and laboratory modalities. PMID- 3094253 TI - Tetracycline-resistant Neisseria gonorrhoeae. PMID- 3094254 TI - [Enteral feeding in the treatment of fistulas of the digestive tract (causes of failure)]. PMID- 3094255 TI - WHO Expert Committee on Malaria. Eighteenth report. PMID- 3094256 TI - Effect of phenobarbital and beta-naphthoflavone on oxidative metabolism of N,N dimethyl-4-aminoazobenzene by regenerating rat-liver microsomes and its response to sulphydryl compounds. AB - The metabolism of the hepatocarcinogen, N,N-dimethyl-4-aminoazobenzene (DAB) is catalysed by selective forms of cytochrome P-450. DAB metabolism has been studied using microsomes from regenerating rat liver prepared 1, 2, 3, 7 and 10 d after partial hepatectomy. Greatly decreased N-demethylation of DAB was seen during liver regeneration, while virtually no effect on ring-hydroxylation was observed. Glutathione stimulated N-demethylation and ring-hydroxylation of DAB, while metabolism of the corresponding secondary amine N-methyl-4-aminoazobenzene (MAB) was not affected. During regeneration, response to the thiol was depressed in the early stages but later returned to normal. beta-Naphthoflavone (BNF) specifically induced N-demethylation of DAB. Induced activity was not depressed during liver regeneration. Phenobarbital (PB) induced total metabolism, which was depressed during regeneration. This indicates greater stability of BNF-induced cytochrome P 450 compared to control and PB-induced cytochrome P-450. The results indicate that during liver regeneration the metabolism of DAB associated with activation (N-demethylation) is depressed, whereas that associated with detoxication (ring hydroxylation) is only slightly affected. This confirms the involvement of different forms of cytochrome P-450 in DAB metabolism. PMID- 3094257 TI - Activities in chick embryos of 7-ethoxycoumarin O-deethylase and aryl hydrocarbon (benzo[a]pyrene) hydroxylase and their induction by 3,3',4,4'-tetrachlorobiphenyl in early embryos. AB - Basal activities of 7-ethoxycoumarin O-deethylase and aryl hydrocarbon (benzo[a]pyrene) hydroxylase were determined in whole-liver homogenates from chick embryos of different ages, from newly hatched chicks and from chicks a few days old. The enzyme activities increased substantially in chick embryo livers between days five and 10, remained at a fairly constant level until day 19, and reached a peak in activity one day after hatching. The optimal pH value was lower than 7.0 for both enzyme activities. The total increase in activity from day five to one day after hatching was about 300-fold for 7-ethoxycoumarin O-deethylase and about 75-fold for aryl hydrocarbon (benzo[a]pyrene) hydroxylase. Treatment of eggs with 3,3',4,4'-tetrachlorobiphenyl resulted in increased metabolism of both substrates by five-day-old chick embryo livers. The increase in aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity was 14-fold while that of 7-ethoxycoumarin O-deethylase was approximately double. PMID- 3094258 TI - The multiple trauma victim: a nutritional cripple. AB - Major trauma often precipitates major malnutrition. In many patients, this malnutrition underlies the morbidity and mortality associated with major injury, often leading to multiple organ failure and refractory sepsis. The clinical challenge is to anticipate these potential nutritional problems and intervene early and appropriately, recognizing that it is far easier to prevent malnutrition than it is to reverse it. PMID- 3094259 TI - [Problems of parenteral feeding in post-aggression metabolism]. PMID- 3094260 TI - [Progress in drug treatment of bronchial asthma]. AB - On the base of modern literature a statement is given on the actual situation of bronchial asthma treatment and its tendencies. It intends to be an instruction for the doctors daily practice and shell help all asthmatics getting the new possibilities of treatment in time. Furthermore these recommendations intend to support a reasonable and scientific prescription of new drugs. PMID- 3094261 TI - Analysis of a co-operative study in finding of mycobacteria. AB - Comparative examinations in finding of mycobacteria carried out in two laboratories of different countries show a superiority of one lab only in one of two series of specimens. That indicates that the results are dependent not only on methods used but also on other factors as the nature of the specimens and the conditions of transport. A critical evaluation is necessary. PMID- 3094262 TI - Evaluation of diaphragmatic contractility in patients with chronic obstructive lung diseases. AB - The indices of diaphragmatic contractility and respiratory ventilation were studied in 31 males with chronic obstructive bronchitis distributed into 2 groups: with hypercapnia (PaCO2 56.3 +/- 0.4 mm Hg) and normocapnia (PaCO2 42.7 +/- 1.4 mm Hg), with reduction of FEV1/VC to 42% and 52% of the due value, Pdimax to 63.4 +/- 5.3 cm H2O and 73.4 +/- 6.1 cm H2O. The plasmatic theophylline concentration 21.19 +/- 1.06 mkg/ml was maintained in five patients with hypercapnia for 10 days by intravenous administration of aminophylline. FEV1 and VC increased by 5% and 8% respectively, Pdimax by 59%, TTdi decreased from 0.10 +/- 0.02 to 0.06 +/- 0.01, and PaCO2--to 44.7 +/- 1.8 mmHg. Vt/Ti did not change significantly. Thus, in patients with irreversible bronchial obstruction the decrease of diaphragmatic contractility leads to the development of arterial hypercapnia. The maintenance of therapeutical concentration of theophylline in blood plasma permits to improve the ventilation function of respiratory muscles and normalize the PaCO2 level. PMID- 3094263 TI - [Population genetic studies in Ethiopia: distribution of blood group polymorphisms in Amhara/Tigrai ethnic groups]. AB - During 1981-1982 and 1983-1984 a population-genetic study has been performed in the Amhara/Tigrai ethnic groups of Northwestern Ethiopia (Gondar). Blood group frequencies are reported for 6 systems (AB0, MNSs, Rh, P, Kell, Kidd), secretor status, haptoglobin, Gc, Gm/Km, HLA-A and -B as well as for the erythrocytic enzyme polymorphisms AcP, PGM1, ADA, EsD, GPT, AK and GLO I. The results are compared with other reports from East Africa and the Arabian peninsula. The mixed caucasoid-negroid gene pool of the Amhara/Tigrai as well as their relations with Arabia are confirmed. PMID- 3094265 TI - Effects of elevated temperatures on the opacity and toxicity of pertussis vaccines manufactured with different inactivating agents. AB - Plain pertussis vaccine manufactured with different inactivating agents was evaluated for its stability at 4-8, 25 and 35 degrees C with regard to the opacity and the toxicity [mouse weight gain test (MWGT) and histamine sensitizing (HS) activity]. Two pools each of heat inactivated pertussis vaccine (HIPV), formaldehyde inactivated pertussis vaccine (FIPV), glutaraldehyde inactivated pertussis vaccine (GIPV), thimerosal inactivated pertussis vaccine (TIPV) and acetone (I) treated pertussis vaccine [A(I)TPV] were taken for the study. The test for determination of opacity and MWGT were performed at monthly intervals for three months and the test for HS activity was performed after three months exposure of the samples at various temperatures. There was almost no loss in the opacity of GIPV and TIPV at all the selected storage temperatures and of HIPV and FIPV at 4-8 degrees C, while A(I)TPV lost about 16% opacity in three months at 4 8 degrees C. At 25 degrees C after three months, the percentage loss in opacity of HIPV averaged about 12, of FIPV 17 and of A(I)TPV 33. At 35 degrees C after three months, the average percentage loss in opacity of HIPV was 16, of FIPV was 25 and of A(I)TPV was 33. Regarding the effect of elevated temperatures on the toxicity of the vaccine, it was observed that the samples held at 35 degrees C for three months were the least toxic followed by those held at 25 and 4-8 degrees C as detected by MWGT and the test for HS activity. PMID- 3094264 TI - [Kinetics of the antibody level in schistosomiasis under chemotherapy]. AB - The antibody level (ELISA) in schistosomiasis much increased one month after therapy. The sanation of the parasitosis within 6 months led to the reduction of the values to the initial level without any further later decrease. The antibody kinetics was the same after successful Niridazol and Praziquantel treatment. When Niridazol failed a second treatment with Praziquantel led to a repeated significant increase. The decrease after the second peak was much steeper and obtained the initial level already 3 months after sanation. Patients with falsely negative ELISA before the treatment reacted partly positive one month after this. One third of all patients examined reacted negatively also at this time. Falsely positive findings in patients from endemic areas (specificity 0.74) seem to be no cross reaction to another affection with helminths, but seem to be traced back to an earlier inapparent schistosomiasis. PMID- 3094266 TI - [Exertion-induced metabolic changes in arterial occlusive diseases with obstruction at different levels]. PMID- 3094267 TI - [Antigenic composition of the gonococcal strains used in preparing a gonorrhea vaccine]. PMID- 3094268 TI - [Current concepts of the blood-brain barrier: neurophysiologic and neurochemical aspects]. PMID- 3094269 TI - Congenital giant diverticulum of the posterior urethra in a 4-year-old boy. AB - A congenital giant diverticulum of the posterior urethra in a 4-year-old boy is reported. The theories on development of congenital urethral diverticula are considered and the importance of the clinical, radiological, endoscopical and histological examination for the differential diagnosis of the acquired diverticula and enlarged utricle is emphasised. In the majority of diverticula transurethral unroofing is most appropriate. The larger and symptomatic diverticula require open excision and eventually urethral reconstruction. Small asymptomatic diverticula may not require any treatment. PMID- 3094270 TI - [Micromethod for the detection of erythrocyte antigens in blood stains]. AB - A micromethod was developed to allow the analysis of blood stains of minor size by the absorption elution technique. The individual absorption, washing, and elution steps were carried out in Beckman tubes containing 5 microliter antiserum. The final agglutination reaction was read through the inverted microscope in microtest plates regularly used for HLA typing. For this final reaction, 2-4 microliter eluate was incubated with 2,000 red blood cells suspended in 1 microliter saline and supplement. For the purpose of standardization, the intensity of agglutination in the microtest plate had to be defined. In comparison to the standard method (tube test and centrifugation), the proposed method proved to be slightly more sensitive with regard to the Rhesus and slightly less sensitive with regard to the AB0 system. With the proposed method very small traces could be successfully analyzed. Thus, two cotton threads 1 mm in length were sufficient for testing antigens A and B, and two cotton threads 2.5 mm in length were enough to detect an Rh antigen. PMID- 3094271 TI - [Effect of influenza virus infection on arachidonic acid cascade in mouse thrombocytes]. AB - Prostaglandins (PGs) are essential for many physiological and pathological processes. As they are not stored in tissue, their presence and actions therefore result from de novo synthesis and release. Although platelets themselves appear to have the ability to synthesize TxA2, PGD2, arachidonic acid may also be metabolized in the lipoxygenase pathway in platelets, producing 12-hydroperoxy/12 hydroxy-5,8,10,14-eicosatetraenoic acid (12-HPETE/12-HETE). CFLP mice were infected intranasally with A/H3N2/Hong Kong (1/68) influenza virus. Platelets were isolated from the control (saline treated) and infected mice 3-13 days after virus application. Platelets were isolated from the diluted arterial blood of the mice. Metabolites of arachidonate cascade were determined using 1-14C-arachidonic acid (2035 MBq/mM spec. act.) as substrate. All incubations were carried out in TC Medium 199 (pH 7.4) at 37 degrees C for 10 min. Radiolabelled products were separated and quantitatively determined. The synthesis of TxA2 in the platelets of animals was found to be significantly increased 7 days after the virus infection. The 12-hydroxy-heptadecatrienoic acid level was higher on the 10th and 13th days of infection, as were the products of the lipoxygenase pathway. PMID- 3094273 TI - [Dislocations and dislocation fractures of the Lisfranc joint--"multiple injury of the foot"]. PMID- 3094272 TI - [Reflections on the use of diagnostic aids in fresh injuries of the ligaments of the upper ankle joint]. PMID- 3094274 TI - [Results following osteosynthesis of intra-articular fractures of the calcaneus]. PMID- 3094275 TI - [Symmetrical bilateral injuries in skiing 1976-1985]. PMID- 3094276 TI - [Treatment concept for 2d- and 3d-degree heat damage to a maximum extent of 18 percent of the surface area in a regional hospital]. PMID- 3094277 TI - [Respiratory loss as a late sequel of blunt chest injuries]. PMID- 3094278 TI - [Diagnosis of insufficiency of the posterior cruciate ligament: value of posterior cruciate ligament phenomena in extension]. PMID- 3094279 TI - [Meniscectomy and costs. A comparison between open and arthroscopic meniscectomy (medical contribution to cost control)]. PMID- 3094280 TI - [Equipment and ski accidents in Switzerland, winter 1983/84]. PMID- 3094281 TI - [Incidence of arthrosis following osteosynthesis of Volkmann's triangle in malleolar fractures]. PMID- 3094282 TI - Antibacterial effect and toxicity of synthesized salicylanilide derivatives. AB - 5 nitro- and chloro-salicylanilide derivatives were synthesized by a simple condensation reaction between phenylsalicylate and the required nitroaniline derivative. The compounds were subjected to direct chlorination in CCl4 without any catalyst and were identified by microanalysis, m. p. and spectral studies. The antibacterial activity was investigated against Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus. The prepared derivatives were evaluated for their acute toxicity on Swiss albino mice. The compounds 5,2'-dichloro-4'-nitrosalicylanilide and salicyl-3'-nitroanilide were the most active against the test organisms, but they showed fluctuating toxicity effect at the dose of 500 mg/kg. The structure-activity relationship and the toxicity tests verified the compound salicyl-4'-nitroanilide as a reasonable antibacterial agent against the four test organisms without any sign of toxicity symptoms up to the dose of 1000 mg/kg. PMID- 3094283 TI - Investigation of aflatoxin contamination in commercial Spanish peanuts. AB - In the present study aflatoxin contamination was investigated with 102 peanut samples. Only 11 samples showed contamination by that mycotoxin. Concentration was less than 15-20 micrograms/kg in all the contaminated samples. Aflatoxin B1, B2, G1, and G2 were detected in the above-mentioned samples. No significant difference was found between shell and shelled peanuts owing to aflatoxin contamination. PMID- 3094284 TI - Effect of root extract from Boerhaavia diffusa L., containing an antiviral principle upon plaque formation of RNA bacteriophages. AB - An extract obtained from the roots of Boerhaavia diffusa plants, which inhibits the infection of several plant viruses, was tested by the agar diffusion hole method for its action on RNA-containing bacterial viruses. Plaque formation of the phages was only partially and non-uniformly influenced by the extract so that a uniform principle of action was not realized for the RNA viruses of prokaryotic and eukaryotic host organisms. PMID- 3094285 TI - [Experimental studies of the significance and mechanism of desensitization to the gonadotropin-inhibiting effect of estrogen. 2. Detection and mechanisms of preovulatory desensitization in the ovarian cycle]. AB - It has recently been demonstrated in women and several mammalian species that the basal LH secretion increases prior to the ovulation-inducing LH surge in spite of a simultaneous rise of the estrogen level in the blood. The temporary relative inefficiency of estrogen in its negative feedback action may be necessary to make adequate gonadotrophic support of final preovulatory follicle maturation possible. To study the mechanisms underlying this phenomenon, the gonadotrophic response to a single injection of estradiol benzoate (EB) was evaluated in acutely ovariectomized adult rats during the different stages of a 4-day ovarian cycle. The results showed that the sensitivity to the gonadotrophin-inhibiting effect of EB is high during late estrus and early metestrus. Between metestrus and diestrus it suddenly declines, and EB did not inhibit the hypophysial gonadotrophin secretion from diestrus through the morning of the subsequent estrus. The cyclic variation of the sensitivity to the negative estrogen feedback is probably not based upon an endogenous rhythm that is independent of the ovarian hormone secretion, because similar variability of the gonadotrophic response to estrogen was not found in rats that had been castrated three days before the injection of EB. A further experiment demonstrated that bilateral implants of EB placed in the medial preoptic area (MPOA) of ovariectomized rats significantly reduced the gonadotrophin-inhibiting effect of s. c. injected estradiol, whereas similar implants located in the mediobasal hypothalamus were completely ineffective in this regard. Since bilateral lesioning of the MPOA in long-term ovariectomized females also lowered the sensitivity to estrogen, the conclusion may be drawn that preovulatory desensitization to the negative estrogen feedback is probably induced in cyclic female rats by an inhibitory effect on medial preoptic neurones of the increase of circulating estrogen recorded in metestrus. In accordance with this assumption, imitation of the periovulatory diminution of estrogen action on the MPOA of intact rats by the removal of medial preoptic EB implants in castrated females during the afternoon of proestrus, resulted in high sensitivity to estrogen during estrus and metestrus. The possible clinical significance of the hitherto not described preovulatory desensitization is briefly discussed. PMID- 3094286 TI - [Infections with penicillinase-producing Neisseria gonorrhoeae in females. Report on 24 cases]. AB - Between the last few weeks of 1980 and March 1985 the susceptibilities of 881 strains of Neisseria gonorrhoeae to penicillin were tested by a simple screening method (disc diffusion test). 76.6% of the isolates were good susceptible, 17.7% moderately susceptible and 5.7% resistant to 3 units of penicillin G. Penicillinase-producing Neisseria gonorrhoeae (PPNG) could be detected in 24 cases (2.7%), most of them between July 1983 and January 1984 (n = 18). 23 patients have been treated successfully with oxytetracycline. All infections had been acquired in the GDR, however, the sources of infection could be firmly traced in 6 cases only. On the basis of the results some clinical and microbiological aspects of infections with penicillin resistant gonococci are discussed. PMID- 3094287 TI - O-serotypes of Pseudomonas aeruginosa from animal and inanimate sources in Saudi Arabia. AB - A total of 1012 samples were examined for Pseudomonas aeruginosa and 257 (25.4%) were positive. The incidence of Ps. aeruginosa in samples collected from animal sources (N = 730) was significantly higher (28.7%) than that in 282 samples of inanimate sources (16.7%). The percentage of samples infected with these organisms was lowest in poultry feed (2.8%) and highest in sewage effluent (57.1%). Nine serotypes were defined from all sources. P5 was the common predominant individual O type in infected chicken navels and in the nasal cavities of Najdi sheep (a Saudi Arabian sheep breed), while P3 and P6 were predominate in the nasal cavities of Somali sheep (a breed imported from Somalia). No Ps. aeruginosa serotype was predominant in sheep faeces. In inanimate sources, P4 was predominant in water and sewage effluent. The isolate from the animal feed was untypeable. In using the slide agglutination technique for serotyping, most of the unusual agglutination reaction types of Ps. aeruginosa (70%) were of strains isolated from Somali sheep. PMID- 3094288 TI - The biochemical basis for the distinction between the two Cryptococcus neoformans varieties with CGB medium. AB - The biochemical basis for the reaction to canavanine-glycine-bromthymol blue (CGB) agar by Cryptococcus neoformans var. gattii and C. neoformans var. neoformans was investigated. All of the var. gattii isolates tested were found to utilize glycine as the sole source of carbon and nitrogen and were resistant to L canavanine. Only 11% of the serotype D isolates of var. neoformans utilized glycine as the sole source of carbon and nitrogen, but these were all sensitive to canavanine. Nineteen percent of the serotype A isolates of var. neoformans were able to assimilate glycine, and 81% of the glycine users were resistant to canavanine. However, these canavanine-resistant, glycine-assimilating, var. neoformans isolates failed to grow when they were cultured on a medium containing glycine and canavanine. Unlike the var. neoformans isolates, all of the var. gattii isolates tested grew on a medium that contained both of these compounds. Glycine-utilizing isolates exhibited good uptake of the amino acid, and a glycine cleaving enzyme was discernable in the isolate. The isolates that fail to utilize glycine accumulated the amino acid at a rate which was barely 15% of that seen in the glycine users, and no glycine-cleaving enzyme was apparent within the 48-hr incubation period. When a cell-free extract (which had been derived from a glycine-utilizing isolate), was incubated with 14C-labeled glycine, ammonia, radiolabeled CO2, and serine were produced. The glycine decarboxylase activity of the cell-free extract was found to be enhanced by the addition of dithiothreitol, tetrahydrofolate, pyridoxal phosphate, and nicotinamide adenine dinucleotide (NAD). The ammonia released during glycine cleavage seems to be responsible for the positive reaction on CGB medium. PMID- 3094289 TI - Enzyme-linked immunosorbent assay in the detection of specific antibodies against Aspergillus in patient sera. AB - A biotin-avidin linked enzyme immunoassay (BALISA) was used to detect Aspergillus fumigatus specific antibodies in the sera of patients with aspergillosis. Culture filtrate antigens from a strain of A. fumigatus grown in synthetic medium was used in the ELISA. This antigen was characterized by various immunochemical methods including isoelectric focusing, two-dimensional electrophoresis and antigen antibody crossed-immunoelectrophoresis. Sera from patients having allergic asthma, allergic bronchopulmonary aspergillosis (ABPA), aspergilloma and normal controls were studied. High levels of IgE and IgG antibodies specific to A. fumigatus antigens were detected in ABPA while only IgG antibodies were seen in aspergilloma. The normal group and the allergic asthma failed to show any differences in the specific antibody content. Biotin-avidin linked immunosorbent assay was found to be very useful in detecting both IgG and IgE antibodies, and by using characterized antigens reproducible and dependable results can be obtained. PMID- 3094290 TI - [Milk progesterone test: instrument for fertility management in cattle]. PMID- 3094291 TI - Extrathyroidal conversion of thyroxine to 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) and its contribution to total triiodothyronines production rates in fed and food restricted piglets. PMID- 3094292 TI - Evaluation of chloral hydrate and magnesium sulphate sedation in buffalo calves (Bubalus bubalis). PMID- 3094293 TI - Cells of sow mammary secretions. III. Some properties of phagocytic cells. PMID- 3094294 TI - Vitamin A- and beta-carotene concentrations in bovine follicular fluid in relationship to follicle size. PMID- 3094295 TI - [Analysis of electrical ventricular systole in sheep. I. Depolarization phenomena]. PMID- 3094296 TI - Systemic effects of topically applied trichothecenes. I. Comparative study of various trichothecenes in mice. PMID- 3094298 TI - Forestomach fluid volume and retention of fluid and particles in the gastrointestinal tract of the camel (Camelus dromedarius). PMID- 3094297 TI - Systemic effects of topically applied trichothecenes. II. Studies with T-2 toxin in rats. PMID- 3094299 TI - [Further development of the hypothesis on the possible formation of pulmonary respiration on the basis of apical gas exchange in the digestive epithelium]. PMID- 3094300 TI - [Tetrathionate reductase as a diagnostic trait in identifying Pseudomonas aeruginosa]. AB - The tetrathionate reductase test may be used for the identification of P. aeruginosa. The most reliable results have been obtained with the use of a medium containing sodium tetrathionate for this purpose, and replacing bromthymol blue used as an indicator for phenol red excludes the possibility of false negative reactions. PMID- 3094301 TI - [Experimental basis for the combined use of tobramycin and immune preparations for treating acute Pseudomonas aeruginosa infections]. AB - The possibility of using tobramycin (Tb) in combination with P. aeruginosa polyvalent corpuscular vaccine (PaPCV) or pyocyanosis hyperimmune plasma (PHP) for the treatment of P. aeruginosa sepsis was experimentally studied. The combined use of Tb and PHP, administered in amounts corresponding to ED50 of each preparation used separately, ensured the survival of 90% of the infected mice, and the injected of PaPCV with ED50 of the antibiotic ensured the survival of 73% of the experimental animals. The combined use of Tb and the two immuno preparations (PaPCV and PHP) for the treatment of P. aeruginosa infection proved to be more effective than their separate administrations. PMID- 3094302 TI - [Immunoenzyme method in the diagnosis of human brucellosis]. AB - The optimum conditions for the determination of specific antibodies in the sera of brucellosis patients by means of enzyme immunoassay (EIA) have been selected. The comparative study of the specificity and sensitivity of EIA and other serological tests has demonstrated that EIA has high diagnostic effectiveness in the diagnosis of acute and chronic brucellosis. The presence of direct correlation between the results of EIA and Coombs' test is observed, which is indicative of the capacity of EIA for detecting both complete and incomplete specific antibodies. It should be pointed out that in all cases the titer of specific antibodies in EIA has been found to be 5-16 times higher than in Coombs' test, the passive hemagglutination test, and agglutination test. PMID- 3094303 TI - [Standardization of the direct hemagglutination reaction induced by bacteria of the genus Lactobacillus]. AB - L. bulgaricus, L. casei var. rhamnosus, and L. plantarum cells grown in agar containing (but not liquid) thioglycol medium for 3 days have been shown to be capable of inducing mannose-resistant agglutination of human and guinea-pig erythrocytes, while giving a considerably weaker reaction with erythrocytes from animals of other species (ox, sheep, dog, rabbit, rat and mouse). The optimum conditions for the test are presented. PMID- 3094304 TI - [Clinico-morphologic description of insufficiency of chemoreceptors of the ventral surface of the medulla oblongata]. AB - Using the method of reversed respiration, a decrease in the sensitivity of the ventilation regulation system to the hypercapnic stimulus was observed in a patient with acoustic neurinoma. Cytological and morphometric study of the tissue sections revealed a decrease in the size and number of neurocytes in the superficial portions of the ventral side of the medulla oblongata. It is concluded that the above structural changes are responsible for inhibition of the metabolic system of respiration regulation. PMID- 3094305 TI - [Descending pathways of the cerebral cortex to nuclear structures of the extrapyramidal system]. AB - The connections of the neocortical structures in animal and human brains with the complex of nuclear formations of the extrapyramidal system have been studied. The authors present comparative characteristics and distribution of these connections in the nuclear and other formations of the extrapyramidal system. Both mediator (via the thalamus) and direct cortical projections toward the nuclei of the extrapyramidal system in primates, especially in humans, have been found to increase. It has been shown that the frontal cortex has closer connections with the complex of the extrapyramidal nuclei as compared with other brain lobes. PMID- 3094306 TI - Regulation of the cysB gene expression in Escherichia coli. AB - It was found by Northern-type hybridization that the amount of RNA, the transcription of which begins at the cysB regulatory gene promoter, is significantly reduced after cysB gene introduction into Escherichia coli on multicopy plasmid. This result indicates that cysB protein inhibits the transcription of its own gene. O-acetyl-L-serine, an internal inducer of E. coli and Salmonella typhimurin cysteine regulons, has no effect on cysB gene expression. PMID- 3094307 TI - Influence of the assay method used on the selection of the most active forms of FSH from the human pituitary. AB - The biological properties of different forms of human pituitary FSH, varying in their molecular charge, were investigated. FSH in two individual human pituitaries and a pool of 30 human pituitaries was extracted and subjected to electrophoresis. From each electrophoresis 14 consecutive fractions with the highest RIA activity were examined with in vitro and in vivo bioassays. The in vitro assay was based upon the estimation of oestradiol produced by cultured Sertoli cells from 10 day old rats. The in vivo bioassay was an hCG augmented test using immature female mice injected on 3 consecutive days. The increase in ovarian weight was the index of response. Both in the individual and in the pooled pituitary material the less negatively charged forms had the highest activity in the in vitro bioassay. In contrast, the more negatively charged forms had the highest activity in the in vivo bioassay. Forms of FSH from each of the two individual pituitary extracts were pooled according to their migration rate and injected iv into mice. The amount of FSH remaining in the circulation of the mouse after 1 h was related to the molecular charge. The highest value was obtained with the pool containing the more negatively charged forms of the hormone. The results indicate that the disappearance rate of the FSH molecule is a dominant factor in the in vivo bioassay. A consequence of these observations will be that the assay method chosen to monitor the purification of FSH will have a major influence on the biological properties of the final preparation. PMID- 3094308 TI - Effect of clomiphene citrate on the in vitro release of LH and FSH by the pituitary gland of the long-term ovariectomized rat pretreated with LRH or with LRH and oestradiol benzoate. AB - The effect of a combined in vivo pre-treatment with luteinizing hormone-releasing hormone (LRH) and either oestradiol benzoate (OB), clomiphene (-citrate) or OB plus clomiphene on the autonomous and the supramaximally LRH-stimulated in vitro secretion of LH and FSH by pituitary glands of long-term ovariectomized (OVX) rats was studied using a hemipituitary perifusion system. The concentration of LRH in the perifusion medium was 1 microgram/ml. Pre-treatment with LRH during 5 days was effected by means of sc implanted Alzet osmotic minipumps; control rats received a piece of silastic with the dimensions of a minipump. OB, 3 micrograms/injection, clomiphene 100 micrograms/injection or solvent were given on days 2 and 4 (day of perifusion: day 5). In rats not pre-treated with LRH neither OB, nor clomiphene changed the content of the pituitary gonadotropin stores. There was only a small but significant positive effect of the combined treatment with OB and clomiphene on the pituitary FSH content. LRH (partly) depleted the gonadotropin stores. This effect of LRH was potentiated by OB, but not by clomiphene. Clomiphene prevented the depletion-potentiating effect of OB. OB raised the LRH-stimulated secretion of LH and FSH as well as the autonomous secretion of LH. Clomiphene raised the LRH-stimulated (not the autonomous) secretion of LH and FSH. OB plus clomiphene had the same effect as OB alone. Clomiphene also raised the LRH-stimulated secretion of LH and FSH after pre treatment with LRH, but OB did not do so: LRH prevented the stimulatory effect of OB but not of clomiphene. OB plus clomiphene had the same effect as OB alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094309 TI - The effect of l-thyroxine treatment on skin accumulation of acid glycosaminoglycans in primary myxoedema. AB - We assessed skin accumulation of acid glycosaminoglycans in ten patients with primary myxoedema (median age 70 years) before and during l-thyroxine treatment (median 7 months). Eight subjects matched for sex and age served as controls. Acid glycosaminoglycans were determined biochemically on small skin biopsies. Hyaluronic acid was elevated in untreated myxoedema, median 0.60, range 0.39-0.90 microgram hexosamine/mg dried defatted tissue compared to a median control value of 0.52, range 0.43-0.65 microgram hexosamine/mg dried defatted tissue, P less than 0.02. Chondroitin-4,6-sulphate and dermatan sulphate showed no elevation, while heparan sulphate was actually reduced in myxoedema, P less than 0.01. l thyroxine treatment induced a significant reduction in hyaluronic acid, median 0.41, range 0.24-0.71 microgram hexosamine/mg dried defatted tissue, while no consistent changes occurred in the remaining three acid glycosamine glycans. The accumulation of hyaluronic acid might contribute to the peculiar non-pitting oedema of the skin in myxoedema, due to the strong water-binding capacity of the substance. PMID- 3094310 TI - The calcium antagonist diltiazem inhibits calcification enhanced by calcitonin in growth cartilage of rats in ethane-1-hydroxy-1,1-diphosphonate (EHDP)-induced rickets. AB - In an animal model of human rickets developed by giving a short-term administration of large doses of EHDP to young rats, concomitant administration of [Asu1,7]eel calcitonin (CT) with EHDP resulted in the promotion of calcification in growth cartilage. In an attempt to clarify the mechanisms related to the accelerated calcification due to CT, the effects of diltiazem, a calcium antagonist, were studied. Diltiazem suppressed, in a dose-dependent manner, the accelerated calcification due to CT in the growth cartilage, as determined by findings on the soft X-ray photos, contact microradiograph and light microscopic histology of the proximal region of the tibia. This suppression was only evident when diltiazem and CT were given concomitantly. If it is assumed that diltiazem inhibits the entry of calcium ion into the cells of growth cartilage, in the same manner as seen in case of smooth muscle and myocardial cells, then our results indicate that intracellular concentrations of calcium might play an important role in the occurrence of accelerated calcification due to CT. PMID- 3094311 TI - [Kinetic studies on indium-111-oxine labelled lymphocytes from patients with chronic lymphocytic leukemia]. PMID- 3094312 TI - [Detection of cytoplasmic mu chain by the double PAP method in cell lines and childhood non-T, non-B ALL cells]. PMID- 3094314 TI - [Mechanism of the interference of the clotting mechanism by IgM type kappa from a patient with macroglobulinemia]. PMID- 3094313 TI - [IgE multiple myeloma. A case report and review of the literature]. PMID- 3094315 TI - [Prealbumin-associated hyperthyroxinemia]. AB - Prealbumin associated hyperthyroxinaemia represents a rare but important protein binding anomaly, causing difficulties in differential diagnostics. This anomaly is based on a variant prealbumin showing an increased affinity to T4 and rT3 and in some cases also when using T4 analogue tracers. The condition of the patient is clinically euthyroid which is confirmed by a normal bTSH level, a normal response to TRH, and peripheral parameters (BMR, ASR, STI, SHBG) in the euthyroid range. This paper describes the diagnostic difficulties in a 45-year-old male pointing out the significance of precise laboratory determination of prealbumin associated hyperthyroxinaemia in order to avoid misdiagnosis and wrong treatment. PMID- 3094316 TI - [Heart rate and arrhythmias in long-term ECG in patients with coronary disease and dilated cardiomyopathy with reference to left ventricular function]. AB - Heart-rate (HR) and arrhythmias (AR) are influenced by the vegetative balance. This cannot be measured during daily life at present. Otherwise HR and AR can be detected with a high accuracy using the Holter-Method (HM). Therefore we investigated the relationship of HR, AR and left-ventricular function (LVF) in patients with coronary heart disease (CHD: 342 HM; normal LVF 33%, moderate reduced 33%, reduced 35%) and dilative cardiomyopathy (DCM: 225 HM, LVF normal 13%, moderate reduced 39%, reduced 48%), with special emphasis on the problem, whether tachycardia during chronic congestion will stimulate AR (AR due to an increased sympathic tone) or will suppress AR (overdrive suppression). Furthermore we evaluated, whether patients with a loss of the circadian pattern (CP) of HR or AR, who demonstrated an uniform high HR (due to the enhanced sympathic tone), were on higher risk of dying than other collectives. HM were analysed using the computer-supported "Multipass-Scanning" system. The decreasing LVF coincides with an increase in HR and a loss of HR-CP (i.e. dHR-day-night greater than or equal to 10 b.p.m.). The amount of the HR-CP depends on the mean HR during day in the manner of a direct relationship. The prevalence of premature ventricular ectopics (PVC) increases with decreasing LVF from 39 to 53% (CHD) and from 47 to 63%. A positive circadian pattern of the PVC exists in 60% of CHD and in 84% of DCM, which also decreases with the LVF to 54 vs. 52%. Independent from a CP in two thirds of the patients VA were stimulated and in one third suppressed with a worsening of the LVF. The phenomenon of an overdrive suppression of VA starts with a HR of 90 b.p.m. and higher. The 40% mortality in patients with an uniform (day and night) high HR (greater than 90 b.p.m.) was significantly higher than in other collectives (10%). PMID- 3094317 TI - Another kind of marathon. PMID- 3094319 TI - Pressure sores: dressings for success. PMID- 3094318 TI - A pastoral care plan for Ottawa Centre. PMID- 3094320 TI - Facilitating the nurse's role as communicator: the design and use of a communication record. PMID- 3094321 TI - Effect of nitrogen on carbon dioxide elimination during continuous flow apneic ventilation in dogs. AB - Continuous endobronchial insufflation of air in paralyzed animals (continuous flow apneic ventilation - CFAV) has been shown to maintain adequate oxygenation and carbon dioxide removal. CFAV in patients using oxygen resulted in adequate oxygenation but a mean rise in PaCO2 of 0.6 mmHg/min (0.08 kPa/min). This experiment compared carbon dioxide removal in dogs with air and oxygen. Ten dogs were anesthetized and paralyzed, and CFAV was used for 1 h with either air or oxygen in a randomized fashion. Adequate oxygenation was obtained with air and oxygen. Normal PaCO2 levels were obtained with air; however, in the animals where oxygen was used, PaCO2 levels rose to a mean of 6.45 +/- s.e. mean 0.4 kPa (48.5 +/- s.e.mean 3.2 mmHg). PMID- 3094322 TI - In vitro release of tegafur from a fatty-base suppository and in vivo bioavailability of tegafur. AB - This study was designed to determine the in vitro release of tegafur from a suppository and the in vivo bioavailability of tegafur in rats. Two different suppository preparations (product A-1 and product A-2) containing 750 mg of tegafur were tested for in vitro release of tegafur by the Muranishi Method (membrane diffusion method) and the partially modified paddle method (permeability through dialysis tubing). When determined by either method, the amount of tegafur released from product A-2 during the whole experimental period was significantly greater than that released from product A-1. When tested by the Muranishi method, however, the difference in the amount released during the first 10-min period was not significant. A greater bioavailability of tegafur after rectal administration was obtained by product A-2 more than product A-1. A significant correlation was observed between the in vitro release and the in vivo bioavailability. The present results indicate that there are considerable differences in physiochemical characteristics between product A-1 and product A 2. PMID- 3094324 TI - Light and electron microscopic visualization of GABAergic elements in the monkey brain by means of a direct GABA antibody. PMID- 3094323 TI - Pituitary-thyroid function and thyrotropin, prolactin and growth hormone responses to TRH in patients with chronic alcoholism. AB - Basal plasma concentrations of thyroxine (T4), 3,3',5-triiodothyronine (T3), free T4 index (TF4I), free T3 index (FT3I) reverse T3, 3,3',5-triiodothyronine (rT3), resin T3 uptake (TR3U), thyroxine-binding globulin (TBG), thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) as well as thyrotropin releasing hormone (TRH) stimulated TSH, PRL and GH were investigated in 31 consecutive male patients (mean age 41 years) with chronic alcoholism. According to the histology of their liver biopsies the patients were divided into three groups: patients with normal livers, steatosis and cirrhosis. The control group consisted of 30 healthy males. The patients had abstained from alcohol for at least one week when studied, and they were on a nutritionally adequate diet. All had consumed a daily minimum of 52 g ethanol for at least 5 years. None of the patients had severe or decompensated liver disease. The patients had significantly reduced T3 and rT3 plasma levels compared to normals. Patients with cirrhosis of the liver had increased TBG and normal RT3U levels, while those without cirrhosis had increased RT3U and normal TBG levels. Plasma concentrations of basal as well as TRH stimulated TSH and PRL were unchanged in alcoholic patients, whereas basal as well as stimulated GH levels were increased in cirrhotic alcoholics. It is concluded that alcohol per se influences T3 levels, but not the part of the hypothalamic-pituitary axis studied, and that the binding proteins are mostly determined by the degree of liver disease. PMID- 3094325 TI - Mechanisms of deoxyguanosine toxicity for human T and B lymphocytes. PMID- 3094326 TI - Synthesis and turnover of purine nucleoside phosphorylase in human lymphocytes. PMID- 3094327 TI - Purine synthetic capacities of de novo and salvage pathways in rat hepatoma 3924A cells. PMID- 3094328 TI - Purine nucleotide synthesis in cultured rat embryos undergoing organogenesis. PMID- 3094329 TI - 5'-Methylthioadenosine (MTA) phosphorylase from promastigotes of Leishmania donovani. PMID- 3094330 TI - Characterization of arabinosylguanine resistance in a lymphoblastoid cell line. PMID- 3094331 TI - Cobalamin inactivation decreases purine and methionine synthesis in cultured human lymphoblasts. PMID- 3094332 TI - 5'-deoxy-5'-methylthioadenosine phosphorylase deficiency in leukemia: genetics and biochemical aspects. PMID- 3094333 TI - Inhibition of de novo purine synthesis by methylthioadenosine. PMID- 3094334 TI - UDP-glucuronyltransferases and their toxicological significance. PMID- 3094335 TI - Multiplicity of cytochrome P-450 in Morris hepatoma. PMID- 3094336 TI - The metabolism of benzene and phenol by a reconstituted purified phenobarbital induced rat liver mixed function oxidase system. PMID- 3094337 TI - Activation of cytochrome P-450 heme in vivo. PMID- 3094338 TI - The formation of N-glucuronides catalyzed by purified hepatic 17 beta hydroxysteroid and 3 alpha-hydroxysteroid UDP-glucuronyltransferases. PMID- 3094339 TI - Activated phase II metabolites: comparison of alkylation by 1-O-acyl glucuronides and acyl sulfates. AB - 1-O-acyl glucuronides are reactive Phase II metabolites which can alkylate chemical nucleophiles. Industrial sulfate ester mixed anhydrides have been reported to be active acylating agents. This study was undertaken in order to establish that sulfate ester mixed anhydrides of clinically useful drugs could be synthesized, purified, and characterized as reactive chemical species. Their ability to alkylate 4-(p-nitrobenzyl)pyridine (NBP) and their stability in aqueous solution was compared with 1-O-acyl glucuronide conjugates of the same drugs. Synthesis of the 1-O-acyl glucuronides of the hypolipidemic agent, clofibric acid, and the nonsteroidal antiinflammatory drugs flufenamic acid and indomethacin were catalyzed by immobilized microsomal rabbit liver UDP glucuronyltransferase. Potassium salts of the sulfate ester mixed anhydrides of these drugs were synthesized chemically by temperature-controlled reaction with chlorosulfonic acid in anhydrous pyridine. Half-lives at pH 2.0, 6.0, 7.4, and 10.0 were determined for each compound. The reactivity of the acyl glucuronides and sulfate ester mixed anhydrides towards the standard chemical nucleophile, 4 (p-nitrobenzyl pyridine (NBP), was measured using a spectrophotometric assay at several substrate concentrations. Acyl sulfate ester mixed anhydrides were shown to be 3-20 times more reactive towards NBP than their corresponding 1-O-acyl glucuronides. For both glucuronides and sulfate esters, relative reactivity towards NBP was: clofibric acid greater than indomethacin greater than flufenamic acid. This behavior paralleled the hydrolytic instability of the compounds. PMID- 3094340 TI - Biological reactive intermediates of mycotoxins. AB - The various reactions involved in the formation and actions of biological reactive intermediates of AFB1 are undoubtedly common to the wide variety of mycotoxins. The structural diversity of mycotoxins and their widespread occurrence in nature has made them a significant class of model environmental toxicants for mode of action studies. Identification of the reactive intermediates of prototype mycotoxins and elucidation of their reactions with molecular receptors will provide information useful for the design of antidotes of other remedial measures and for a better understanding of the mechanisms of action of comparable environmental toxicants. This type of studies will also permit the more precise biochemical analyses to be applied to the assessment of health risk due to exposure to mycotoxins. PMID- 3094342 TI - Stereoselectivity of rat liver cytochrome P-450 isozymes: direct determination of enantiomeric composition of K-region epoxides formed in the metabolism of benz[a]anthracene and 7,12-dimethylbenz[a]anthracene. AB - The K-region 5,6-epoxides of benz[a]anthracene (BA) and 7,12 dimethylbenz[a]anthracene (DMBA) were isolated by normal-phase HPLC from metabolites formed by incubation of the respective parent compound with liver microsomes from untreated (control), phenobarbital (PB)-treated, and 3 methylcholanthrene (MC)-treated rats in the presence of an epoxide hydrolase inhibitor, 3,3,3-trichloropropylene 1,2-oxide. The enantiomeric contents of the metabolically formed K-region 5,6-epoxides of BA and DMBA were directly determined by chiral stationary phase HPLC. The K-region 5,6-epoxides formed in the metabolism of BA have (5R,6S): (5S,6R) enantiomer ratios of 25:75 (control), 21:79 (PB), and 4:96 (MC), respectively. In contrast, the (5R,6S):(5S,6R) enantiomeric ratios of the K-region 5,6-epoxides formed in the metabolism of DMBA are 76:24 (control), 80:20 (PB), and 97:3 (MC), respectively. These and earlier results on the stereoselective K-region metabolism studies of 7 methylbenz[a]anthracene and 12-methylbenz[a]anthracene indicate that cytochrome P 450 isozymes exhibit different stereoselectivities in the K-region epoxidations of BA and DMBA and a methyl substituent at the C12 position of BA alters the stereoheterotopic interactions between cytochrome P-450 isozymes and the BA molecule. PMID- 3094341 TI - Acetaminophen as a cosubstrate and inhibitor of prostaglandin H synthase. PMID- 3094343 TI - Clofibrate selectively induces azoreduction of dimethylaminoazobenzene (DAB) by rat liver microsomes. PMID- 3094344 TI - Chemistry of metabolites of thioureas. PMID- 3094345 TI - Antibodies as probes of cytochrome P450 isozymes. PMID- 3094346 TI - Enzyme catalysed cleavage of the N-N bond of N-nitrosamines. PMID- 3094347 TI - Altered expression of oncogenes in mouse epidermis following exposure to benzo(a)pyrene diol epoxides. PMID- 3094349 TI - Small-bowel obstruction due to an intestinal balloon: treatment by percutaneous needle puncture. PMID- 3094348 TI - Adrenalectomy modifies the effect of intracerebral histamine on the cold stimulated TSH secretion in male rats. AB - Cold-stimulated TSH secretion remained normal after adrenalectomy in conscious male Sprague-Dawley rats, but the inhibitory effect of a small dose of histamine (1.0 micrograms/rat into the 3rd ventricle, i.c.v.) on the TSH secretion was abolished. Adrenaline (0.01-1.0 mg/kg s.c.) inhibited dose-dependently the cold stimulated TSH secretion. However, although adrenalectomy causes a prominent decrease in releasable adrenaline, a larger dose of histamine (2.5 micrograms/rat i.c.v.) decreased the TSH secretion. The effect of histamine was not modified after pretreatment with either corticosterone or dexamethasone, irrespective of whether intact or adrenalectomized rats were studied. Corticosterone decreased and dexamethasone increased the cold-stimulated TSH secretion when given intraperitoneally. Chlorisondamine (10 mg/kg i.p.), a peripheral ganglionic blocking drug, suppressed the TSH cold-response in intact rats. Histamine (1.0 microgram/rat i.c.v.) had no additional inhibitory effect after chlorisondamine. The results suggest that the effect of intracerebral histamine on cold-stimulated TSH secretion is caused neither by stimulation of the hypothalamus-pituitary adrenocortical axis nor by increased adrenomedullary catecholamine release. Further, the effect of intracerebral histamine is obviously not due to enhanced neurosympathetic activity. The effect of histamine is modified by adrenalectomy, but the adrenal glands are not essential for it. PMID- 3094350 TI - A comparison of techniques for improved visualization of the arteries of the distal lower extremity. AB - Intraarterial prostaglandin E1, tolazoline, nitroglycerin, and tourniquet-induced reactive hyperemia were directly compared by paired analysis for their efficacy in improving visualization of distal lower extremity vessels during routine arteriography in 101 limbs (52 patients). Nitroglycerin and reactive hyperemia were equal in their effect and statistically superior to both tolazoline and prostaglandin E1. Tolazoline was superior to prostaglandin E1, which had little or no effect. Intraarterial nitroglycerin in a dose of 200 micrograms appears to be the method of choice for augmenting visualization of the distal arterial vascular system in lower-extremity arteriography. PMID- 3094351 TI - Postoperative recurrence of lung cancer: detection by whole-body gallium scintigraphy. AB - The records were reviewed of 111 consecutive patients who had lung cancer resected and who were followed with serial postoperative whole-body gallium scans. Scans were obtained preoperatively at intervals of 3-6 months for about 1 year after surgery and subsequently at yearly intervals. The period of follow-up varied from 1 1/2 to 8 years. Of 55 patients who developed tumor recurrence, a gallium scan was the first indicator of recurrence in 11 (20%) and was judged helpful in confirming or localizing a recurrence in another 14 patients (25%). False-positive rates were determined from 175 postoperative scans in the other 56 patients who did not suffer recurrence. Of these 175 scans, 15 (9%) demonstrated abnormalities that were sufficiently suspicious that an additional diagnostic procedure, other than chest radiography, was performed for clarification. However, in no case did the gallium scan result adversely affect the management of the patient. Our data demonstrate that routine postoperative whole-body gallium scanning can facilitate early detection of recurrence in some cases. Judicious use of gallium scanning in cases with clinically suspected recurrence can enable prompt localization, diagnosis, and treatment of recurrent tumor. PMID- 3094352 TI - Flecainide: a new antiarrhythmic agent. AB - PVCs (trigger mechanisms) and the vulnerability of the myocardium to sustain a life-threatening ventricular tachycardia (substrate) are two variables in the sudden death equation. Physicians treating patients at risk for sudden death should consider PVC frequency and vulnerability as interrelated variables. Risk assessment must take into consideration both variables. Antiarrhythmic drug efficacy can be assessed in terms of a reduction in trigger mechanisms (PVCs) as well as decreasing myocardial vulnerability (induction of VT at PES). Flecainide acetate, at a reduced dosage of 100 mg twice daily, is effective in both aspects, markedly decreasing PVC frequency and preventing VT induction at PES testing. Holter monitoring and electrophysiologic testing evaluate different aspects of the problem. With the addition of an agent as potent as flecainide, which is devoid of many of the bothersome side effects previously limiting antiarrhythmic therapy, an agent is now available that may be useful to treat both the trigger mechanism and the substrate in sudden death. We must be careful not to worsen the situation through the profound effects of flecainide on depolarization and refractoriness that in some patients cause life-threatening arrhythmias to be more frequent. PMID- 3094353 TI - Mild hypertension: the rationale for treatment. PMID- 3094354 TI - Dose-dependent thrombolysis, pharmacokinetics and hemostatic effects of recombinant human tissue-type plasminogen activator for coronary thrombosis. AB - The pharmacokinetics, thrombolytic profile and effects on hemostasis of graded intravenous doses of recombinant human tissue-type plasminogen activator (rt-PA) were studied in 45 patients with acute myocardial infarction. Infusion of rt-PA at a rate of 4 to 8.3 micrograms/kg/min resulted in plateau levels of the drug in plasma of 0.52 to 1.4 micrograms/ml. A linear relation between infusion rate and plasma rt-PA concentration was observed, although plasma drug levels varied substantially among subjects who received infusions at the same rate. The ratio between plateau levels of rt-PA in plasma and infusion rate was inversely related to initial distribution volume (7.3 +/- 2.9 liters, n = 21). The decline in plasma concentration of rt-PA, x(t), as a function of time after cessation of the infusion, was described adequately by the biexponential equation: x(t) = 0.71exp( 0.13t) + 0.29exp(-0.015t). The initial and terminal half-lives of rt-PA in the blood were 5.3 +/- 1.7 and 46.2 +/- 14 minutes, respectively. The efficacy of rt PA for coronary thrombolysis was dose-dependent. With 4 micrograms/kg/min of rt PA for 90 minutes, no reperfusion was achieved, whereas infusion rates of 5 micrograms/kg/min or more for 90 minutes accomplished reperfusion in more than 80% of the patients. However, the frequency of occurrence of residual intraluminal thrombus was significantly lower with an infusion rate of 7 micrograms/kg/min for 90 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094355 TI - Efficacy and safety of nicardipine for chronic, stable angina pectoris: a multicenter randomized trial. AB - Nicardipine, a new calcium channel blocking drug of the dihydropyridine family, was administered to 63 patients at a dose of 30 or 40 mg 3 times daily in a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Nicardipine midly increased heart rate (HR) at rest and midly decreased the blood pressure (BP) at rest. When generally similar responses to the 30- and 40-mg doses were averaged, nicardipine produced a 7% increase in peak exercise HR, which was balanced by a 6% decrease in peak exercise BP. Thus, no change occurred in the exercise HR-BP product. With nicardipine, treadmill exercise duration increased 9%, time to angina increased 15%, time to 1-mm ST-segment depression increased 16%, and oxygen consumption at peak exercise increased 13%. Mean anginal frequency declined, as did mean weekly sublingual nitroglycerin consumption, but not significantly. There were more cardiovascular side effects with nicardipine than with placebo, with at least 3 patients having increased angina judged by investigators as probably related to the drug. Vasodilatory side effects were also more frequent with nicardipine, but were generally mild and well tolerated; the drug had to be discontinued in only 1 patient, because of vasodilatory effects. Nicardipine is effective and generally well tolerated in patients with chronic stable angina. PMID- 3094356 TI - Comparison of acute hemodynamic effects of nitroglycerin versus diltiazem and combined acute effects of both drugs in angina pectoris. AB - Fifteen patients with exertional angina underwent hemodynamic monitoring and measurement of cardiac output during a control treadmill exercise test. They were then randomized to receive sustained-release nitroglycerin, 13 mg (group I) or placebo (group II). Repeat exercise testing revealed that in group I, both maximal oxygen consumption and cardiac output increased significantly. In group II neither maximal oxygen consumption nor cardiac output increased significantly. All patients then received diltiazem, 60 mg, and repeat testing was carried out 1 hour later. In group I maximal oxygen consumption and cardiac output were higher than control, but were no higher than after nitroglycerin. In group II, maximal oxygen consumption increased significantly, but the increase in cardiac output was not significant. Thus, sustained-release nitroglycerin, 13 mg, or diltiazem, 60 mg, both improve exercise performance, but the combination does not improve exercise performance to an extent greater than either drug alone. PMID- 3094357 TI - Fever and malnutrition: endogenous pyrogen/interleukin-1 in malnourished patients. AB - The effect of protein-calorie malnutrition on the release of endogenous pyrogen/interleukin-1 (EP/IL-1), the protein responsible for the induction of fever, was investigated in 18 hospitalized patients with chronic malnutrition. Monocytes from the 18 patients and from 19 healthy controls were cultured overnight after stimulation with Staphylococcus epidermidis. The presence of EP/IL-1 was tested by injecting culture supernatants into rabbits and measuring the maximum febrile response (delta Tmax). Malnourished patients produced significantly less EP/IL-1 than controls (delta Tmax = 0.27 +/- 0.04 degrees C for patients vs 0.49 +/- 0.03 degrees C for controls, p less than 0.001). The poor febrile response in the malnourished patients was related to low serum albumin and retinol-binding protein, but not to thyroxine-binding albumin or lymphocyte number. This abnormality may help explain the poor febrile response often noted in hospitalized debilitated patients. PMID- 3094358 TI - The toxic impact of parenteral solutions on the metabolism of cells: a hypothesis for physiological parenteral therapy. AB - The prescribing of parenteral fluids has become so routine that most physicians have become oblivious to the toxic impact of current practices on the cellular metabolism of their patients. Few physicians recognize the iatrogenic threat of replacement of body fluids based solely on concepts of volumetric and caloric need. Understanding the metabolic and ionic organization of cells can provide the physician means to use parenteral fluids to control the inherent metabolic energy of cells. Application of new insight into physical chemistry and metabolic properties of the cell can enhance the physician's therapy of the critically ill patient. PMID- 3094359 TI - Protein deficiency in premature infants receiving parenteral nutrition. AB - A classical finding of protein deficiency is hair depigmentation, or the flag sign. To determine the clinical conditions that predispose ill premature infants to the development of protein deficiency, we compared the clinical courses and nutritional histories of premature infants receiving parenteral nutrition who developed the flag sign (group F), with those of a matched control group (Group C). Occurrences of necrotizing enterocolitis (NEC) and consequent surgery were significantly higher in group F than in group C (p less than 0.002 and p less than 0.005, respectively). No differences were found in the mean (+/- SD) administration of amino acids (group F, 2.5 +/- 0.2 g X kg X day vs group C, 2.4 +/- 0.4) and total energy (83.4 +/- 13.4 kcal X kg X day vs 83.6 +/- 11.1, respectively). Mean serum albumin levels (2.6 +/- 0.4 g/dL vs 2.6 +/- 0.5, respectively) also were similar. Because infants in both groups received recommended amounts of protein, results suggest that infants who have NEC, and surgery as a consequence of NEC, require more protein than is presently recommended. PMID- 3094361 TI - Capillary hemangioblastoma. An immunohistochemical study. AB - Previous studies using immunohistochemical methods to determine the presence of glial fibrillary acidic protein (GFAP) and Factor VIII-related antigen (FVIIIR:Ag) in stromal cells of capillary hemangioblastomas have yielded conflicting results with respect to the possible astrocytic and endothelial origins of these cells. This study included Ulex europaeus I lectin (UEAI), a more sensitive marker of endothelial cells. Antibodies were also used as markers of pericytes and a variety of markers were employed to identify different populations of histiocytes. Results of this investigation indicate that FVIIIR:Ag and UEAI are limited only to endothelial cells, and that GFAP is present in entrapped astrocytes only. Positivity of stromal cells was found with some of the histiocytic markers, but the authors were unable to conclude that these cells have a histiocytic origin. It was concluded that currently there is no evidence that stromal cells are derived from endothelial, pericytic, or astrocytic cells their origin remains uncertain. PMID- 3094362 TI - Cyclophosphamide-induced water intoxication: treatment with fluid restriction and 2-mercaptoethane sulfonate. PMID- 3094360 TI - Controlled evaluation of fat intake in the Mediterranean diet: comparative activities of olive oil and corn oil on plasma lipids and platelets in high-risk patients. AB - Activities of low-fat diets with olive oil or corn oil on lipids and platelets were studied in 23 middle-aged patients with high atherosclerosis risk for 8 wk. The olive oil diet had a polyunsaturated-saturated ratio of 0.33 vs 1.28 for the corn oil diet. Plasma total cholesterol was reduced with corn oil, but high density lipoprotein cholesterol levels were lower with corn oil and unchanged or raised by olive. Plasma apolipoprotein B levels were equally reduced by both diets; apolipoprotein AI and the apo AI:B ratio rose only with olive oil. Plasma glucose levels were lowered significantly with olive oil. Changes in platelet function were characterized by a reduced sensitivity to arachidonic acid (particularly with corn oil) and to collagen (particularly with olive). An olive oil diet with a moderate fat intake (about 30% of total calories) leads to favorable plasma lipoprotein and platelet changes. PMID- 3094363 TI - An unusual case of dysphagia: esophageal intramural pseudodiverticulosis. AB - A 30-yr-old man presented with chronic dysphagia and a questionable upper gastrointestinal hemorrhage. On endoscopic evaluation, numerous openings were seen throughout the esophagus. Barium esophagram confirmed the diagnosis of esophageal intramural pseudodiverticulosis. The clinical presentation and the endoscopic, radiographic, histopathological, and manometric data are presented. Our findings illustrate common esophageal conditions associated with this rare entity. PMID- 3094364 TI - Secretory piece and IgA deficiency in a patient with Waldenstrom's macroglobulinemia. AB - A case of a patient suffering from Waldenstrom's macroglobulinemia who developed diarrhea and mild steatorrhea is described. Laboratory studies revealed low serum IgA, intestinal secretory IgA deficiency, and small intestine bacterial overgrowth as demonstrated by the C14-cholylglycine breath test. These findings suggest that selective IgA deficiency and secretory component deficiency may be contributing factors in the development of diarrhea in Waldenstrom's macroglobulinemia. PMID- 3094365 TI - In vitro effects of gammaglobulin (IgG) on human monocyte Fc receptor function. I. Effect on monocyte membrane-associated IgG and Fc receptor-dependent binding of antibody-coated platelets. AB - Intravenous immunoglobulin (IV IgG) has been reported to be clinically beneficial for the treatment of immune thrombocytopenic purpura (ITP). The mechanism of effect still remains unknown. We examined the in vitro effects of two commercially available IV IgG preparations. Exposure of normal monocytes to IgG in vitro produced a significant increase in monocyte-bound IgG. Prior treatment of the commercial IgG preparations by filtration through a 0.2-micron Millipore filter or ultracentrifugation caused a dramatic decrease in IgG bound to the monocyte surface, indicating that IgG aggregates were responsible for this effect. Exposure of monocytes to IgG levels as high as 150 mg (Sandoglobulin) and 400 mg (Gamimune) did not result in a statistically significant inhibition of monocyte-platelet interaction as examined by a morphologic rosetting assay. Thus, despite the ability of IV IgG preparations to cause substantial increments in monocyte surface IgG, impairment of Fc receptor-mediated monocyte binding of antibody-coated platelets was not observed. PMID- 3094366 TI - Characterization of purine nucleoside phosphorylase in leukemia. AB - Purine nucleoside phosphorylase (PNP) activity was determined in mononuclear cells from 49 patients with various types of leukemia. A low level of PNP activity was found in mononuclear cells from patients with acute myeloid and lymphoblastic leukemia and with chronic lymphocytic leukemia. Enzymatic and immunological studies on PNP from leukemic cells of these patients revealed no differences in Michaelis constant for inosine, thermostability, electrophoretic mobility, immunological reactivity, or specific activity between the PNP of leukemic cells and that of normal mononuclear cells. These results suggest that the decrease in PNP activity of leukemic cells is due to a decreased rate of enzyme synthesis. Thus, the abnormality of PNP activity might be due to an alteration in the regulatory mechanism of enzyme synthesis in the purine metabolism in the leukemic clone. PMID- 3094367 TI - Antibodies to microbial antigens in various farmer populations. PMID- 3094368 TI - Stability of vitamins in total parenteral nutrient solutions. PMID- 3094369 TI - Sublingual burning not a valid index of nitroglycerin potency. PMID- 3094370 TI - Strategic planning for clinical services: Hamot Medical Center. AB - As a result of a two-day strategic-planning program, a hospital pharmacy department developed a five-year plan for addressing seven critical issues facing the department. The pharmacy department at a large nonprofit community hospital began a formal planning process in 1981 after concluding that the existing clinical services had been implemented in a haphazard fashion and had mixed results. The planning process began with a two-day planning program aimed at identifying issues facing the department, followed by the development of consensus about the most important issues and the development of action plans for dealing with these. The planning program consisted of four parts: presentations by hospital administrators, nurses, and the medical staff on future directions in their respective areas and pharmacy's potential input; presentations on the future of pharmacy from the perspectives of the pharmacy director and the responsible hospital administrator; preliminary recommendations related to drug distribution services and clinical services by two pharmacy consultants; and discussions of departmental management issues and key points identified in previous sessions. The department's progress in addressing each of the seven critical issues is described; most of the action plan has been completed. The consensus-building planning process allowed the department to focus on the most important issues, identify support and possible conflicts from others, and obtain administrative approval of the department's focus on patient-oriented services. PMID- 3094371 TI - Providing 24-hour nutrient infusions to critically ill patients. AB - The outcome of critically ill patients receiving total parenteral nutrient (TPN) therapy was evaluated, and the percentage of wasted TPN solutions administered as one-per-day (2- or 3-L) or multiple-per-day (750-mL or 1-L) infusions was determined. Between March 31 and June 1, 1984, all patients who were treated by the nutritional support service (NSS) and who met the study criteria were included in the study. The 24-hour nutrient content of each TPN solution was determined using a published method. Patient outcome was determined using TPN therapy data that were collected from the patients' medical charts and NSS records. To determine waste, all discarded TPN solutions were recorded. A total of 20 patients (10 men and 10 women) were included, representing 23.6% of the 76 patients who received TPN therapy during the study period. Study patients received 24-hour nutrient solutions for a mean of 16.4 +/- 12.9 days and required a mean of 3.9 +/- 4.6 days to reach sufficient metabolic stability to qualify for 24-hour infusions. During the study period, 56 (2.8 +/- 2.5 per patient) orders were changed. The percentage of wasted TPN solutions was low; 4.3% (17 of 1326) multiple-per-day and 1.7% (5 of 292) one-per-day solutions were wasted. Twenty four-hour TPN solutions can be used successfully in critically ill patient populations. PMID- 3094372 TI - Arachidonic acid prevents hyperglycemia-associated yolk sac damage and embryopathy. AB - Light microscopic, electron microscopic, and morphometric studies were performed on rat conceptuses cultured between day 10 and day 12 in normal, hyperglycemic, arachidonic acid-supplemented normal, and arachidonic acid-supplemented hyperglycemic rat serum. The results were compared with those of 12-day-old conceptuses grown in utero. No major differences were observed between in vivo and in vitro control conceptuses. Arachidonic acid supplementation of control culture medium resulted in an improvement of conceptus development. Addition of 20 micrograms/ml of arachidonic acid to an otherwise teratogenic hyperglycemic serum medium (950 mg/dl of D-glucose) prevented the malformations induced by hyperglycemic conditions: open neural tube, advanced neuropil formation in the neuroepithelium, significant reduction of rough endoplasmic reticulum, decreased size and number of lipid droplets, and increased number of lysosome-like structures in the visceral endodermal yolk sac cells. PMID- 3094373 TI - Diagnostic related groups and the obstetrician: antepartum admission. AB - A retrospective review was conducted of all pregnant women discharged undelivered during fiscal year 1985. If the current Medicare prospective payment plan were applied to these admissions, Diagnostic Related Group 383 (other antepartum diagnoses with medical complications) and Diagnostic Related Group 384 (other antepartum diagnoses without medical complications) would together generate a negative cash flow. Supplementation for capital costs and direct and indirect medical education costs would result in a positive cash flow; however, the supplementation is vulnerable to political and social forces that will tend to diminish or eliminate it. PMID- 3094374 TI - Fetal blood volume responses to acute fetal hypoxia. AB - The purpose of this study was to explore the effects of acute hypoxia on the volume of blood circulating in the fetus. The oxygen content of air inspired by chronically catheterized, near-term pregnant sheep was reduced and supplemented with carbon dioxide in an attempt to maintain fetal carbon dioxide tension constant. Control fetal arterial oxygen tension averaged 22.3 +/- 0.7 (SE) mm Hg. During a 30-minute hypoxic period, reductions in fetal arterial oxygen tension by 2.4 to 12.5 mm Hg in individual animals were associated with decreases in fetoplacental blood volume of 1.1% to 14.3%. On the average (n = 14), fetal blood volume decreased by 6.7% +/- 0.8% when oxygen tension decreased by 7.7 +/- 0.9 mm Hg. Both arterial and venous pressures increased significantly during the hypoxic period. Upon the return to breathing of room air, there was a transient overshoot of fetal PO2 of 1.0 +/- 0.4 mm Hg at 10 minutes, but fetal blood volume did not return to normal until 30 minutes after the hypoxia. Thus, the data suggest that acute fetal hypoxia causes rapid and sustained reductions in fetal blood volume whereas volume returns to normal only slowly after elimination of the hypoxia. PMID- 3094375 TI - Nuclear magnetic resonance measurement of cytosolic free calcium levels in human red blood cells. AB - Red blood cells were loaded with 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N' tetraacetic acid (FBAPTA) by incubation with 50 microM of the acetoxymethyl ester (FBAPTA-AM), and cytosolic free Ca2+ was monitored with 19F-nuclear magnetic resonance (NMR). Loading with 50 microM FBAPTA-AM, which results in a final FBAPTA level of approximately 0.5 mM, caused only a 25-30% fall in cell ATP as measured by 31P-NMR when 5 mM pyruvate was present. Leakage of the NMR active Ca2+ indicator, which results from cell lysis, was corrected for with the addition of extracellular Eu3+ ions, extracellular ethyleneglycol-bis(beta aminoethylether)-N,N'-tetraacetic acid (EGTA), or washing. With this method, we have found basal levels of cytosolic free Ca2+ averaging 61 +/- 6 nM (means +/- SE, n = 19). When the intracellular level of FBAPTA was varied from 0.1 to 1.0 mM, there was no correlation between the level of cytosolic free Ca2+ and the level of loading with FBAPTA. Addition of 10 microM of the Ca2+ ionophore A23187 with extracellular Ca2+ set at different levels by Ca2+-EGTA buffers caused an increase in cytosolic free Ca2+ as expected. Furthermore, ATP depletion caused a two- to three-fold increase in cytosolic free Ca2+, consistent with inhibition of Ca2+ efflux via that Ca2+-ATPase. PMID- 3094376 TI - Measurement of cytoplasmic free Ca2+ concentration in cultured muscle cells by aequorin and quin 2. AB - Ca2+ has been proposed to regulate expression of the gene for the Ca2+ pump of the sarcoplasmic reticulum in developing chicken myoblasts (A. N. Martonosi, L. Dux, R. L. Terjung, and D. Roufa. Ann. NY Acad. Sci. 402: 485-514, 1982. In the present study, intracellular free Ca2+ ([Ca2+]i) was measured with the photoprotein, aequorin, incorporated by a reversible hyperpermeabilization technique, and with the fluorescent probe, quin 2. Because aequorin reacts irreversibly with Ca2+ and is inactivated by heat, at 37 degrees C the active aequorin content declined markedly. The resting glow (1/10(6) of the maximum light) disappeared after a few hours, whereas the light from the total active aequorin remaining was still detectable when cells were lysed 3 days later. A new approach, which compared the rate of disappearance of aequorin in treated and control cells, was developed on the basis that aequorin would be inactivated more quickly in cells with higher [Ca2+]i. A23187, ionomycin, and trifluoperazine, all of which accelerated gene expression (A. N. Martonosi et al.), increased the rate of decay of active aequorin and therefore increased [Ca2+]i. "Ca shock", and ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid, which also increased the gene expression (A. N. Martonosi et al.), caused small increases of [Ca2+]i not detectable by aequorin but detectable by quin 2. X537A and ouabain had no effect on the gene expression (A. N. Martonosi et al.) and did not raise [Ca2+]i. The results support the proposal that Ca2+ may regulate expression of this gene. PMID- 3094377 TI - Adipocyte glycogen synthase and pyruvate dehydrogenase in obese and type II diabetic subjects. AB - To determine whether 1) insulin stimulates pyruvate dehydrogenase (PDH) and glycogen synthase (GS) in isolated human adipocytes and 2) adipocytes from subjects with obesity or noninsulin-dependent diabetes mellitus (NIDDM) are resistant to the effects of insulin, PDH and GS were assayed in adipocytes from 11 control, 8 obese, and 9 NIDDM subjects. Basal PDH activities were 123 +/- 20, 129 +/- 21, and 128 +/- 25 pmol pyruvate oxidized/min per 2 X 10(5) adipocytes in these groups. Insulin stimulated PDH activity to a maximum of 223 +/- 38 pmol/min per 2 X 10(5) in adipocytes from control subjects, but did not significantly increase values from obese subjects. Insulin significantly decreased PDH activity in cells from NIDDM subjects (99 +/- 20 pmol/min per 2 X 10(5) cells, P less than 0.05). PDH activity assayed with high magnesium and calcium concentrations was significantly stimulated by insulin in adipocytes from control, but not obese or NIDDM subjects. GS assayed with 1 mM glucose 6-phosphate did not differ significantly among control, obese, or NIDDM subjects (446 +/- 110, 451 +/- 156, and 291 +/- 35 pmol incorporated into glycogen, respectively). Insulin significantly stimulated glycogen synthase in all three groups (827 +/- 179, 764 +/- 177, and 569 +/- 51 pmol incorporated) to a similar extent. Glycogen synthase assayed with 10 mM glucose 6-phosphate was decreased in NIDDM (1,335 +/- 131 pmol incorporated) compared with obese or control subjects (2,512 +/- 451 and 2,239 +/ 230 pmol incorporated, respectively, P less than 0.01). PMID- 3094378 TI - Hormonal regulation of postprandial induction of gastrointestinal ornithine decarboxylase activity. AB - The growth of gastrointestinal mucosa can be related to ingestion and digestion of diet, with fasting producing mucosal hypoplasia and hyperphagia producing mucosal hyperplasia. Experiments were designed to determine whether induction of polyamine metabolism following ingestion of a meal was related to mucosal growth. Activity of the enzyme ornithine decarboxylase (ODC) in both jejunum and ileum but not in duodenum was dependent on the presence of food in the gut; ODC activity was more than 200-fold greater in mucosa of fed rats than in fasted rats. Inhibition of ODC with difluoromethylornithine lead to mucosal atrophy in ileum but not in duodenum. Refeeding of fasted rats resulted in significant induction of ODC in duodenal, ileal, and colonic, but not fundic, mucosa. In addition, two hormones, epidermal growth factor and glucagon, were effective inducers of ileal ODC activity. Direct evidence for hormonal involvement in the postprandial rise in mucosal ODC activity was provided by experiments in rats that had undergone ileal bypass surgery. After refeeding of fasted rats mucosal ODC activity was induced in both ileum left in continuity and in the bypassed segment. Refeeding of elemental diets demonstrated that ingestion of carbohydrate alone was sufficient for maximal enzyme induction. Mixed amino acids or glyceryl trioleate were no more effective inducers than nonnutritive solutions of cellulose or saccharin. These data demonstrate that hormones which are released during ingestion and digestion of a meal are the stimuli for induction of mucosal polyamine metabolism, suggesting that food-induced mucosal growth is hormonally mediated. PMID- 3094379 TI - Hepatic heme and drug metabolism in rats with chronic mountain sickness. AB - Rats chronically exposed to hypobaric conditions develop pulmonary hypertension, right heart failure, hemoglobinemia, and in preliminary studies were recently found to have increased hepatic cytochrome P-450 content and activity of heme oxygenase, the rate-limiting enzyme for heme breakdown. To further delineate effects of chronic hypoxic, hypobaric exposure, on hepatic physiology and biochemistry, we have studied heme and drug metabolism in male Sprague-Dawley rats exposed to hypoxic conditions for 4-5 wk. Hypoxia, produced by exposure of rats to room air under hypobaric conditions (approximately 380 Torr), caused marked polycythemia [hematocrit (Hct) 70% vs. control Hct 43%], plasma hemoglobinemia, depletion of plasma haptoglobin, and decreased hemopexin concentrations. It also led to significant (20-30%) increases in concentrations of total hepatic heme and microsomal cytochrome P-450 and increased activities of heme oxygenase. In contrast, activity of 5-aminolevulinate synthase, the rate limiting enzyme of hepatic heme synthesis, was significantly decreased in hypoxic rats and was not as inducible as in control normoxic rats. Hypoxia did not alter the rest of the heme synthetic pathway, as shown by a normal rate of conversion of 5-aminolevulinate to heme. Hypoxic exposure had no effect on the concentration of hepatic cytochrome-b5 but decreased activity of NADPH-cytochrome c reductase. Rates of metabolism of aminopyrine, benzphetamine, ethoxyresorufin, and warfarin were similar in hepatic microsomes obtained from hypoxic and normoxic rats. Thus the oxygen-requiring processes of hepatic heme and drug metabolism were well maintained despite chronic profound hypoxia sufficient to cause cardiopulmonary complications. PMID- 3094380 TI - Differences in uptake and esterification of saturated analogues of cholesterol by rat small intestine. AB - Coprostanol and cholestanol are two saturated analogues of cholesterol. The former, which is the A/B ring isomer of cholesterol, is a nonabsorbable sterol, whereas the latter, which has an A/B ring configuration closer to that of cholesterol, is absorbed only half as efficiently as cholesterol. Intestinal mucosal cell uptake and esterification, two important steps in absorption, were studied in vivo after feeding the sterols and in vitro using everted sacs of rat small intestine. The results showed that the intestinal tissue content of coprostanol, total and esterified, were significantly lower than that of cholestanol. Total cholesterol concentration in the intestinal tissue was similar throughout but the esterified cholesterol content increased significantly throughout the length of the intestine compared with controls. The study suggests that cholestanol is absorbable because its uptake and esterification are not limited, whereas coprostanol is nonabsorbable because its uptake and esterification are limited in the intestinal mucosa. Also, the two sterols stimulate the activities of cholesterol esterase, one of the cholesterol esterifying enzymes, in the intestinal mucosa. The present study along with previous studies suggests that the structure of the sterol molecule as a whole appears to be the important determinant for its uptake and esterification, and probably absorption, in the small intestine. PMID- 3094381 TI - Uptake pathways for amino acids in mouse intestine. AB - This paper characterizes amino acid (AA) uptake pathways in an everted-sleeve preparation of mouse jejunum. AA uptake is linear with time for 2-4 min, depending on the particular AA and its uptake rate. Escape of tracer to the serosal surface is still negligible at these times. Errors due to metabolism of labeled AAs to volatile products can be minimized by using 14C- rather than 3H labeled AAs and by not drying tissues before counting. The dependence of AA uptake on concentration shows saturable kinetics, with apparent Km values in the range 1-4 mM. By 25 or 50 mM an uptake plateau is reached for leucine, lysine, methionine, and methylaminoisobutyric acid but not for aspartic acid, histidine, or proline. Proline kinetics are the result of a saturable Na+-dependent component, a linear diffusional component, and possibly a small saturable Na+ independent component. The Na+-dependent component of uptake for six AAs averages 83% of the total at 0.01 mM and 54% at 25 or 50 mM. Leucine and D-glucose exhibit modest (32%) cross-inhibition of Na+-dependent uptake. For the same six AAs we determined the percent inhibition of both the Na+-dependent and the Na+ independent components by the other AAs. These results suggest the presence of at least five or six AA uptake pathways in mouse jejunum: distinct Na+-dependent pathways for acidic, basic, and neutral AAs and for imino acids; a shared Na+ independent pathway for basic and neutral AAs; and possibly a Na+-independent pathway for acidic AAs. Comparisons of AA uptake pathways in mouse, rabbit, and rat intestine reveal many similarities but also some differences. PMID- 3094382 TI - Effects of phorbol esters on sodium and chloride transport in rat colon. AB - To determine the role of protein kinase C in the regulation of active electrolyte transport in rat descending colon, the effects of phorbol dibutyrate (PDB) were studied using the Ussing chamber/voltage-clamp technique. PDB added to the serosal surface increased the short-circuit current in a concentration dependent manner with a EC50 of 3 X 10(-8) M and a maximal effect at 10(-7) M PDB. The effect was not seen with the inactive alpha-phorbol analogue but was reproduced with 1-oleoyl-2-acetylglycerol, a more permeable analogue of diacylglycerol. PDB caused a decrease in mucosal-to-serosal and net fluxes of Na and Cl and an increase in serosal-to-mucosal Cl flux, indicating inhibition of Na and Cl absorption and stimulation of Cl secretion. The PDB-induced increase in Cl secretion was virtually abolished by both indomethacin and ibuprofen, indicating a dependence on arachidonic acid metabolism via the cyclooxygenase pathway. The Cl secretion was inhibited by verapamil and Ca2+-free bathing solution on the serosal surface but not by dantrolene, suggesting the importance of extracellular Ca2+ but not intracellular stored Ca2+ in the PDB-induced secretion. The Cl secretory effect was also inhibited by tetrodotoxin and atropine, suggesting involvement of cholinergic nerves. In contrast, the PDB-induced decrease in Na and Cl absorption was not dependent on metabolites of the cyclooxygenase pathway, not dependent on extracellular Ca2+, and not blocked by tetrodotoxin. It appears likely that protein kinase C is involved in the regulation of rat colonic active Na and Cl absorption and electrogenic Cl secretion but that the pathways involved are different in the two transport systems. PMID- 3094383 TI - Functional significance of exaggerated renal thromboxane A2 synthesis induced by cyclosporin A. AB - Animals and humans undergoing a chronic treatment with cyclosporin A (CyA) show a reduction in glomerular filtration rate (GFR). The cause of this abnormality has not been established. Since CyA interferes with arachidonic acid (AA) metabolism in various cells, we wished to determine whether alterations in renal AA metabolites contribute to deteriorating renal function in rats on CyA. We show that chronic CyA treatment induces a progressive increase in the renal synthesis of thromboxane (TX) A2. This is a selective abnormality in that CyA does not influence the renal synthesis of prostaglandin E2 (PGE2) and prostacyclin (PGI2). A significant negative correlation has been found between TXB2 urinary excretion rate and inulin clearance. No correlation has been observed between TXB2 excretion and p-aminohippuric acid clearance. The withdrawal of CyA is followed by a normalization of both TXB2 urinary excretion rate and GFR. The administration of a selective TXA2 inhibitor, UK-38,485, resulted in a significant reduction in urinary excretion of TXB2 accompanied by a significant increase in GFR. We conclude that chronic treatment with CyA in rats is associated with a selective increase in renal TXA2 synthesis and suggest that this abnormality may play a role in the reduction of GFR. PMID- 3094384 TI - Relationships between calcium and chloride transport in frog skin glands. AB - Frog skin gland, a furosemide-sensitive Cl(-)-secreting epithelium, exhibits Cl( )-dependent Ca2+ secretion in response to stimulation by beta-adrenergic agonists. In this study, we further explored the relationships between Cl- and Ca2+ secretion in frog skin using 45Ca fluxes and short-circulating technique. On addition of isoproterenol (ISO) or 8-(p-chlorophenylthio)-cAMP, a significant positive correlation was demonstrated between Ca2+ secretion and Cl- secretion. Because Cl- transport in other Cl(-)-transporting epithelia may be modulated by prostaglandins or by changes in cytosolic Ca2+ activity, in addition to modulation by cAMP, we also examined the effects of prostaglandins (PG)E2 and F2 alpha, indomethacin (INDO), and the calcium ionophore A23187. Treatment with PGE2, PGF2 alpha, or A23187 at a dose of 10(-5) M resulted in marked stimulation in the amiloride-resistant short-circuit current, a reflection of Cl- secretion. This current was inhibited by furosemide addition or removal of Cl- from the bathing medium. However, and in contrast to stimulation with ISO or cAMP, PGE2, PGF2 alpha, and A23187 failed to induce Ca2+ secretion. In addition, the stimulation of Cl- secretion by A23187 was abolished by INDO (10(-6) M) pretreatment. Thus frog skin glands secrete Cl- via two mechanisms: one mediated by beta-adrenergic-cAMP stimulation and the other by activation of prostaglandin metabolism induced by changes in cytosolic Ca2+. Only the former pathway is associated with Ca2+ secretion. Furthermore, to account for the Cl- dependence of Ca2+ secretion, we postulate the existence of a Ca2+-Cl- cotransport system stimulated by cAMP. PMID- 3094385 TI - Lysine uptake by rat renal brush-border membrane vesicles. AB - Lysine uptake by isolated rat renal brush-border membrane vesicles occurs via a single saturable system plus a significant diffusion component with indication of a single energy of activation on an Arrhenius plot. Initial uptake is not sodium dependent, and intravesicular accumulation of lysine at longer time points is greatest in the absence of sodium. Accumulation levels differ in the presence or absence of NaCl or choline chloride and are specific for the cation used. Lysine uptake is membrane potential sensitive and inhibitable by cystine, dibasic amino acids, and cycloleucine. Heteroexchange diffusion of lysine with cystine and lysine with arginine occurs, but no heteroexchange occurs with cycloleucine, indicating that lysine shares a transport system with cystine and dibasic amino acids but not with cycloleucine. PMID- 3094386 TI - O2 radicals in arachidonate-induced increased blood-brain barrier permeability to proteins. AB - We studied the effect of topical application of arachidonate on the brain surface on blood-brain barrier permeability to either 125I-labeled human albumin or to horseradish peroxidase administered intravenously. Arachidonate was applied under a cranial window, and the concentration of albumin was measured in brain after elimination of the blood by perfusion-fixation. Permeability to 125I-labeled albumin was increased in the superficial 4 mm of the cortex but not in the deeper cortical layer 4-6 mm from the surface. This increased permeability to albumin was prevented by simultaneous topical application of superoxide dismutase (60 U/ml) and catalase (40 U/ml). Alterations in vascular permeability to horseradish peroxidase were evaluated in semiquantitative fashion, and they behaved similarly. Extravasated horseradish peroxidase was found in the wall of penetrating arterioles, and to a lesser extent in the wall of intraparenchymal vessels and capillaries, but not in the wall of pial arterioles or veins, although these latter vessels displayed focal endothelial lesions. We conclude that arachidonate increases the blood-brain barrier permeability to proteins. This increase in permeability is mediated by O2 radicals. The increased permeability occurs primarily in penetrating arterioles and not in pial arterioles or veins. PMID- 3094387 TI - The failure of diagnosis-related groups. PMID- 3094389 TI - The psychotherapies: benefits and limitations. AB - The promises and challenges of the psychotherapies today are explored in the areas of treatment, training, diagnosis, research, and review. Benefits discussed include advances in the science and standardization of psychotherapy assessment and practice; improved research tools for establishing therapeutic efficacy; development of new clinical modalities, especially short-term techniques; cooperative efforts to combine and integrate diverse methods of treatment; establishment of ethical codes of conduct for the therapist; and the application of computerized evaluation and cost-containment procedures. At the same time, limitations reflect the various conceptual confusions, research inadequacies, identity crises, political pressures, and economic constraints of the field. Of particular concern is the current "age of accountability" which has placed cost effectiveness at the pivot of public policy in mental health care. PMID- 3094388 TI - Thyrotropin-releasing hormone and dementia. PMID- 3094390 TI - Client transfers in long-term care: five years' experience. AB - This paper reports the home-facility and level of care changes, discharges, and deaths over a five-year period for 1,653 clients newly admitted in 1978 to a long term care program in British Columbia, Canada. Five years after admission, of clients initially admitted to care at home (N = 1241), 34.3 per cent were still in the program (14.5 per cent unchanged; 6.7 per cent at home but at a higher level of care, and 11.7 per cent in facilities). Of the remainder, 38.9 per cent had died and 26.8 per cent had been discharged. Findings for those initially admitted to care in facilities (N = 412) are remarkably similar. After five years, 28.4 per cent of these clients were still in the program; 39.3 per cent had died. Moves from facility to home care were few (2.4 per cent). Despite their advanced age at admission (mean = 74.7, S.D. 14.6), one-third were still in the program five years later, some with status virtually unchanged. PMID- 3094392 TI - Acute sporadic hepatitis in adults living in Cairo, Egypt. AB - A group of 295 adult male patients from Cairo, Egypt, with acute hepatitis were studied. Acute hepatitis A was diagnosed in 8 patients (2.7%), hepatitis B in 115 (38.9%), delta infection in 19 (6.4%) and possible Epstein-Barr virus or cytomegalovirus-mediated hepatitis in 7 patients (2.4%). The remaining 146 patients (49.5%) were considered to have hepatitis non-A non-B. The clinical presentation of the various causes of hepatitis was similar, although patients with hepatitis B and delta infection had significantly higher mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels than patients diagnosed as having hepatitis non-A non-B. Various risk factors for the acquisition of hepatitis were evaluated. A history of an injection for medical treatment and a history of anti-schistosomal therapy were significantly associated with delta infection when compared to patients with either hepatitis B or non-A non-B (P less than 0.05). Hepatitis non-A non-B is a major cause of acute hepatitis in adults living in Cairo, and an iatrogenic source of infection may be important in the epidemiology of delta infection. PMID- 3094391 TI - Risk of hepatitis B infection among Egyptians infected with Schistosoma mansoni. AB - Three hundred twenty-four individuals in a farming village located in the Nile Delta of Egypt were serially tested for hepatitis markers and Schistosoma mansoni to determine whether there is an increased risk of hepatitis B in persons infected with schistosomiasis. One-half of the subjects had stools positive for S. mansoni. Thirty-seven percent of the individuals had been infected with hepatitis B, and 3% were chronic HBsAg carriers. No statistical association was found between S. mansoni infection and hepatitis B infection, including chronic hepatitis B. Although there was no evidence of an association between these 2 pathogens, larger nonhospital based studies are needed to resolve this question. PMID- 3094393 TI - An outbreak of Chagas' disease in southwestern Bahia, Brazil. AB - An outbreak of 20 cases of acute Chagas' disease followed the movement of Triatoma infestans into the county of Riacho de Santana, Bahia, Brazil. The outbreak was unusual in that the majority of cases occurred in adults. Vector control measures were implemented. Three years after the outbreak, a rural community was examined to determine the extent of human infection and disease due to Trypanosoma cruzi. Ninety of 440 residents (20.5%) had serologic evidence of infection, but rates of electrocardiographic (EKG) abnormalities were low. Comparison of age-specific rates of seropositivity and EKG abnormalities with rates from areas with endemic Chagas' disease supported the hypothesis of a recent epidemic. Control measures appear to have interrupted transmission in the region. PMID- 3094395 TI - Daily urinary protein loss in Schistosoma haematobium infection. AB - Proteinuria was studied in 128 children aged 6 to 18 years with Schistosoma haematobium infection in the People's Republic of Congo. Urinary protein concentration in spontaneously voided midday urine of patients with greater than 100 ova/10 ml was significantly higher than in 24-hr urine specimens. Median daily urinary protein loss in patients with moderate intensity of infection (100 350 ova/10 ml) was 300 mg and 584 mg/1.73 m2 body surface in heavily infected patients (greater than 350 ova/10 ml). A significant correlation existed between egg excretion at noon and protein concentration in spontaneous urine samples as well as daily urinary protein loss (r = 0.76 and r = 0.68, respectively). Heavily infected patients had a daily protein loss of up to 3.3 g/1.73 m2, total serum protein and albumin concentration, however, were within normal limits. This may indicate adaptive mechanisms in patients with urinary schistosomiasis and high proteinuria which maintain a balanced serum protein concentration. PMID- 3094394 TI - Protection against fatal murine Chagas' disease with a Leishmania braziliensis panamensis stock. AB - Past attempts to immunize mice against a fatal Trypanosoma cruzi infection utilizing related hemoflagellates have been unsuccessful. In the present study, C57BL/6 mice received a footpad inoculation of 10(7) promastigotes of Leishmania braziliensis panamensis. Six and 9 weeks subsequent to this inoculation mice were infected intraperitoneally with the Tulahuen strain of T. cruzi. All immunized mice survived infection over the 6-month period of observation whereas control mice regularly died. There was an early transient T. cruzi parasitemia in the immunized mice. Culture of blood and organs as well as histopathological examination of various organs 6 months post-challenge failed to yield any evidence of T. cruzi. Heat-killed and freeze-thawed extracts of promastigotes did not confer any protection. These observations raise the possibility that certain leishmanial species might confer natural protection against a T. cruzi infection and that this information could be useful in the development of a vaccine. PMID- 3094396 TI - [Decrease in bleeding using injectable glyceryl trinitrate during corrective surgery of spinal deformities. A comparative study of 200 cases]. PMID- 3094397 TI - Valproic acid in neonatal status convulsivus. AB - Valproic acid infused rectally was successful in controlling seizures in two neonates who failed to respond to conventional anti-convulsive therapy. We suggest that this drug may be a useful adjuvant in difficult cases of status convulsivus in neonates. PMID- 3094398 TI - Macromelanosomes in the early diagnosis of neurofibromatosis. AB - Skin biopsies of cafe-au-lait macules from 34 patients with a clinical diagnosis of classical neurofibromatosis were examined histologically and ultrastructurally to determine the presence or absence of macromelanosomes in the epidermal melanocytes and keratinocytes. Sixteen of the 34 patients had macromelanosomes. The presence of macromelanosomes varied with age and ethnic background; they were detected in nine of 12 Whites, six of 10 persons of mixed ancestry, and one of two Blacks. In these populations skin biopsy is useful in early diagnosis of neurofibromatosis. However, none of 10 persons of Indian stock had macromelanosomes. Their total absence in this group may be indicative of genetic heterogeneity. PMID- 3094399 TI - Quantification of azo-coupled lysine in azo proteins by amino acid analysis. AB - Hydrochloric acid hydrolysis of azo proteins in which lysine residues are azo coupled, results in conversion of modified lysines to alpha-amino-epsilon-hydroxy caproic acid plus alpha-amino-epsilon-chloro caproic acid. The latter can interfere with the determination of tyrosine by amino acid analysis. This potential problem can be avoided either by making basic and then neutralizing HCl hydrolysates or by hydrolyzing the protein in methane sulfonic acid. PMID- 3094400 TI - Analysis by high-performance liquid chromatography of hyaluronic acid and chondroitin sulfates. AB - The use of high-performance liquid chromatography for the quantification of glycosaminoglycan disaccharides has been hampered by the inability to isocratically resolve the chondroitinase digestion products 2-acetamido-2-deoxy-3 O-(beta-D-gluco-4-enepyranosyluronic acid)-D-glucose (delta Di-HA) and 2 acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-D-galactose (delta Di-OS). To overcome this limitation, we have developed a solvent system capable of resolving delta Di-HA, delta Di-OS, 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4 enepyranosyluronic acid)-6-O-sulfo-D-galactose (delta Di-6S), and 2-acetamido-2 deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (delta Di-4S). Integrator responses were linear from 1 microgram down to 25 ng for delta Di-HA, delta Di-OS, and delta Di-4S and down to 100 ng for delta Di-6S. This method was used to examine changes in the content of urinary hyaluronic acid and chondroitin sulfates isolated from normal individuals and from patients with Lowe Syndrome, Werner Syndrome, and Hutchinson-Gilford Progeria Syndrome. We confirmed that the HPLC method gave results comparable to colorimetric methods. PMID- 3094401 TI - Measurement of 13CO2/12CO2 abundance by nondispersive infrared heterodyne ratiometry as an alternative to gas isotope ratio mass spectrometry. PMID- 3094402 TI - Crypt production in normal and diseased human colonic epithelium. AB - New crypts are added continuously to the adult mouse intestinal epithelium by a process of crypt replication. Branching crypts found in the epithelium represent a stage in the process of crypt replication. In "normal" human colonic epithelium we found a small but definite percentage of branching crypts, 0.44 +/- 0.16, indicating that new crypts are being produced at a low rate in this epithelium. Significantly higher (P less than .001) percentages of branching crypts, 30.4 +/- 5.75, 15.1 +/- 1.08, and 13.2 +/- 1.05, were found in diseased colonic epithelium from patients with ulcerative colitis, Crohn's disease, and multiple polyposis, respectively. These results may be interpreted as suggesting that the rate of crypt production in human colonic epithelium is increased in a number of disease states. We concluded that, as in the mouse intestinal epithelium, the rate of the crypt replication process in human colonic epithelium is plastic and may respond to a variety of conditions. PMID- 3094403 TI - Intermittent positive pressure ventilation with either positive end-expiratory pressure or high frequency jet ventilation (HFJV), or HFJV alone in human acute respiratory failure. AB - Continuous Positive Pressure Ventilation (CPPV), High-Frequency Jet Ventilation (HFJV), and a combination of HFJV with Intermittent Positive Pressure Ventilation (CV) were randomly compared in 13 critically ill patients with severe acute respiratory failure. Ventilatory settings were chosen in order to apply the same mean airway pressure (Paw) during the three modes. Respiratory frequencies were adjusted during CPPV (16 +/- 2 breaths/min) and HFJV (235 +/- 32 breaths/min) to achieve the same level of PaCO2 and were then combined during CV. All patients were heavily sedated during the study and had had peripheral and balloon-tipped pulmonary arterial catheters previously inserted. After a steady state at FIO2 1 in each mode of ventilation, hemodynamic and respiratory parameters were measured. A Paw of 13.8 +/- 2.9 mm Hg was applied to each patient by using a PEEP of 7.4 mm Hg during CPPV; a driving pressure of 2.9 +/- 0.2 bars and an I/E ratio of 0.43 during HFJV; and by combining HFJV, using a driving pressure of 1.2 +/- 0.3 bars with intermittent positive pressure ventilation during CV. There were no significant differences in any of the hemodynamic or respiratory parameters measured, except for a significant decrease in PaCO2 during CV when compared to CPPV or HFJV. We concluded that 1) arterial oxygenation and cardiac output depend mainly on Paw independent of the method used to increase Paw and 2) CV can improve CO2 elimination without increasing Paw.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094404 TI - Constant flow ventilation in anesthetized patients: efficacy and safety. AB - Constant flow ventilation (CFV) maintains normal gas exchange in apneic dogs and has potential clinical application during thoracic surgery or pulmonary edema. We compared CFV and intermittent positive pressure ventilation (IPPV) in five healthy, anesthetized, (fentanyl, diazepam, and nitrous oxide) and paralyzed patients undergoing nonthoracic operations. Constant flow ventilation was delivered at a total flow of 0.9-1.6 L . kg-1 . min-1 (nitrous oxide-oxygen at 1:1) into two tubes of 2.5-3.5 mm inner diameter attached to each side of an 8-9 mm inner diameter orotracheal tube (OTT). Under bronchoscopic guidance, the CFV OTT was advanced to position each ventilating tube at a mainstem bronchial orifice. Gas exhausted through the OTT lumen. If intrathoracic pressure exceeded a preset limit, a solenoid valve automatically interrupted gas flow to the patient to prevent barotrauma. Compared to IPPV, during CFV for up to 30 min average PaCO2 increased to 69.2 +/- 14.5 from 35.9 +/- 2.9 mm Hg, reflecting a calculated alveolar ventilation (VA) of 46 +/- 22% of the eucapnic level. We suggest that a technique combining CFV at lower flow rates with IPPV may prove clinically useful by allowing decreased tidal volume and inspiratory pressure while maintaining normal VA. PMID- 3094405 TI - High frequency positive pressure ventilation during general anesthesia for extracorporeal shock wave lithotripsy. PMID- 3094406 TI - Dose-response curves and pharmacokinetics. PMID- 3094408 TI - Frequency response of long mass-spectrometer sampling catheters. AB - It was hypothesized that the long lengths of sampling catheters required when a mass spectrometer is multiplexed to more than one operating room limit the upper frequency at which a gas concentration may be determined accurately. This possibility has not been investigated. Known step changes of CO2 were generated by a solenoid valve driven by an electronic timer that was adjustable from 0.1 to 10 Hz. The valve alternated between 100% O2 and 7% CO2 in 50% O2 and balance N2. CO2 concentration was monitored by a mass spectrometer after the gas passed through a 3.7 m Teflon catheter or through 30 m Teflon, nylon, polyethylene (PE), or polyvinylchloride (PVC) catheters. Gas flow for all catheters was adjusted to 1.1 ml/s. The peak-to-peak output of the mass spectrometer was read from a storage oscilloscope. The 3.7 m catheter caused a 10% error at 5.5 Hz (330/min). In sharp contrast, 30 m catheters made from Teflon, PVC, and PE caused errors greater than 10% at only 0.6 Hz (36/min). The 30 m nylon catheter passed 1.1 Hz (66/min) with a 10% error. Teflon, PVC, and PE are not suitable materials from which to make long catheters sampling CO2. Because the frequency response of the nylon catheter appeared similar to that of a low-pass filter, an electronic circuit was designed and tuned to extend the high-frequency response of the catheter. With the circuit in place, the frequency at which a 10% error occurred in the measurement of CO2 improved from 1.1 Hz (66/min) to 2.2 Hz (132/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094407 TI - Plasma concentrations of alfentanil required to supplement nitrous oxide anesthesia for general surgery. AB - To design an efficient infusion regimen from pharmacokinetic data, it is necessary to know the alfentanil plasma concentrations required for satisfactory anesthesia. In 37 patients about to undergo lower abdominal gynecologic, upper abdominal, or breast surgery, anesthesia was induced with alfentanil 150 micrograms/kg iv and 66% N2O in oxygen. Thereafter, N2O anesthesia was supplemented with a continuous infusion of alfentanil that was varied between 25 and 150 micrograms X kg-1 X h-1, as indicated by the patient's responses to surgical stimulation. Small bolus doses of alfentanil 7 or 14 micrograms/kg were administered and the infusion rate increased to suppress precisely defined somatic, autonomic, and hemodynamic responses. Arterial plasma concentrations of alfentanil were measured during the operation when the patient did and did not respond to noxious stimulation. Logistic regression was used to determine plasma concentration-effect curves for different stimuli. Plasma alfentanil concentrations required along with 66% N2O to obtain responses to single episodes of stimulation in 50% of the 37 patients (Cp50 +/- SE) were: 475 +/- 28 ng/ml for tracheal intubation, 279 +/- 20 ng/ml for skin incision, and 150 +/- 23 ng/ml for skin closure. Between skin incision and closure, multiple determinations of response/no response were made for each patient and an individual Cp50 was estimated. The Cp50 (mean +/- SD) for the three surgical procedures were: breast, 270 +/- 63 ng/ml (n = 12); lower abdominal, 309 +/- 44 ng/ml (n = 14); and upper abdominal, 412 +/- 135 ng/ml (n = 11). The Cp50 for satisfactory spontaneous ventilation after the discontinuation of N2O was 223 +/- 13 ng/ml. These data demonstrate that different perioperative stimuli require different alfentanil concentrations to suppress undesirable responses. Thus, the alfentanil infusion rate should be varied according to the patient's responsiveness to stimulation in order to maintain satisfactory anesthetic and operative conditions and to provide rapid recovery of consciousness and spontaneous ventilation. PMID- 3094410 TI - Mycoplasma pneumoniae is a frequent cause of exacerbation of bronchial asthma in adults. AB - The possible role of infection with Mycoplasma pneumoniae (MP) in exacerbation of bronchial asthma in adults was studied in 95 patients hospitalized due to acute asthma. Twenty (21%) of these patients had evidence of a recent MP infection as determined by the presence of high levels of MP-specific IgM antibodies. In addition, high levels of both IgM and IgG but not IgA serum immunoglobulins were observed in the MP-infected group as compared to a control group of 20 non-MP infected asthmatics. Five out of 20 MP-infected asthmatics exhibited rheumatoid factor (RF) in their sera while patients in the control group were all negative for RF. It is concluded that MP infection may be significant in exacerbation of asthma in adults. PMID- 3094411 TI - Protective effect of disodium cromoglycate on allergen-induced bronchoconstriction and increased hyperresponsiveness: a double-blind placebo controlled study. AB - The protective effect of 40 mg cromolyn on allergen-induced late response and increased hyperresponsiveness were studied in five asthmatic children to whom this drug and saline placebo were administered 20 minutes before allergen inhalation, at random, double-blind. Cromolyn reduced the magnitude of early and late responses and abolished the increase in methacholine responsiveness. PMID- 3094409 TI - Linkage between the porcine genes encoding immunoglobulin heavy-chain allotypes and some serum alpha-protease inhibitors: a conserved linkage in pig, mouse and human. AB - Linkage between the genes coding for immunoglobulin heavy-chain allotypes and some serum alpha-protease inhibitors was demonstrated in pigs by means of segregation data in families. A recombination frequency of about 8% was estimated. This represents evolutionary conservation of an autosomal linkage group as linkage between the homologous loci has previously been reported, in humans and in mice. PMID- 3094412 TI - Surface proteins of Breda virus. AB - The serotypes 1 and 2 of Breda virus from feces of experimentally infected gnotobiotic calves were studied with respect to their sedimentation and density properties in sucrose gradients and their structural polypeptides; Berne virus, the proposed prototype of the new family Toroviridae, was included for comparison. After Breda-1 virus had been stored at 4 C for a prolonged period, it showed a heterogeneous sedimentation behavior (480 to 520 Svedberg units [S]) and density (1.18 to 1.21 g/ml) indicative of its poor state of preservation. In contrast, freshly prepared Breda-2 virus sedimented at 350 S and showed a buoyant density of 1.18 g/ml; these values compare well with those of Berne virus (400 S and 1.16 g/ml, respectively). Efficient purification of the Breda viruses could be achieved by a 2-step method, involving pelleting by ultracentrifugation followed by isokinetic and isopyknic sucrose gradient centrifugation. Radioiodinated purified virus showed polypeptides with apparent molecular weights of 105,000, 85,000 37,000, and 20,000; another labeled protein of 65,000 D is of doubtful virus specificity. Mouse immune serum raised against Breda-2 virus recognized the polypeptides of the homologous virus and the 2 highest molecular weight proteins of Breda 1 virus in radioimmune precipitation. The same serum inhibited hemagglutination of the heterologous serotype to a low, but significant, degree and efficiently neutralized the infectivity of Berne virus. These observations are taken as indications that the 105,000- and 85,000-D polypeptides represent surface structures of torovirions, probably peplomeric proteins. PMID- 3094413 TI - Pathophysiology of small testes in beef bulls: relationship between scrotal circumference, histopathologic features of testes and epididymides, seminal characteristics, and endocrine profiles. AB - Tissue sections from testes and epididymides obtained from 17 young beef bulls with scrotal circumference (SC) between 27 and 40.5 cm were studied to determine whether small testes were a manifestation of lesions or a result of less, but otherwise normal, seminiferous epithelium. The SC correlated negatively with the estimates of germinal epithelial loss and positively with seminiferous epithelial area. Four bulls with SC less than 30 cm had severe lesions in their testes. Hypoplastic tubules were characterized by Sertoli's cells only with no evidence of germinal cells. Loss of germinal cells, leaving vacuolated epithelium and atrophy, were observed in degenerated tubules. Hyperplasia of Leydig's cells was observed in the vicinity of Sertoli's cell-only tubules, resulting either from degeneration or hypoplasia, and atrophy of Leydig's cells was associated with tubules devoid of Sertoli's cells. These findings indicated that Sertoli's cells may produce a factor(s) required for maintenance and regulation of Leydig's cell function. Epididymal epithelium, especially in the head, had regressed in bulls with hypoplastic and degenerative changes in their testes. Decreased sperm concentration and motility and an increased frequency of morphologic defects were observed in the 4 bulls with testicular lesions and regressed epididymal epithelium. Blood plasma profiles of cortisol, follicle-stimulating hormone, luteinizing hormone, and testosterone were determined in the 4 bulls with SC less than 30 cm and 10 of the 13 bulls with SC greater than 30 cm. There were no statistically significant (P greater than 0.1) differences in the responses to exogenous gonadotropin-releasing hormone or base-line patterns of blood plasma follicle-stimulating hormone and luteinizing hormone between the 2 groups. However, in the bulls with SC less than 30 cm, the mean concentration of testosterone was lower, whether spontaneous (P less than 0.05) or exogenous gonadotropin-releasing hormone induced (P less than 0.1). The fact that these bulls were not deficient in gonadotropins indicated that Leydig's cell function was impaired by local factors, either the factors that caused the tubular damage or those consequent to the tubular damage. PMID- 3094414 TI - Pseudomonas cepacia in cystic fibrosis patients. PMID- 3094415 TI - Body weight and respiratory muscle function in chronic obstructive pulmonary disease. PMID- 3094416 TI - Field evaluation of enzyme-linked immunosorbent assay for the serodiagnosis of tuberculosis. AB - An enzyme-linked immunosorbent assay (ELISA) was evaluated as a serodiagnostic test for active tuberculosis in La Paz, Bolivia. ELISA was compared with sputum smear in 277 persons presenting to the Instituto de Torax and was used for screening in 1,458 military personnel. The test was performed under field conditions on 4-microliter samples of capillary blood obtained by finger prick. ELISA was found to have a sensitivity of 69% and a specificity of 88%. Sputum smear had a sensitivity of 79% and a specificity of 100%. ELISA was found to have undiminished sensitivity and specificity in patients who were sputum-negative, and the two tests could be combined to achieve a sensitivity of 92% and specificity of 88%. Positive and negative predictive values were highest for populations with tuberculosis prevalences in the range of that seen among patients presenting to the Instituto de Torax in Bolivia, but ELISA also led to the diagnosis of tuberculosis in 5 of 1,458 soldiers tested in the screening program. PMID- 3094417 TI - Platelet-activating factor causes pulmonary vasodilation in the rat. AB - Although platelet-activating factor (PAF) has generally been found to be a pulmonary pressor substance, its vasoactivity has not been measured at low doses in a preconstricted pulmonary vascular bed. Thus, we examined the effects of low concentrations of PAF on systemic and pulmonary hemodynamics during normoxia and acute hypoxia in conscious, catheterized rats (weighing 250 to 350 g), on hypoxic vasoconstriction in isolated rat lungs, and on norepinephrine-induced constriction in isolated, intact, and endothelium-denuded rat pulmonary arteries. In normoxic rats, injections of 0.001, 0.01, 0.1, and 1.0 microgram PAF/rat given intravenously caused progressively greater, transient systemic hypotension and tachycardia. The 2 higher doses also decreased cardiac output and pulmonary arterial pressure (Ppa). In 5 rats breathing 8% O2, Ppa fell from 36 +/- 2 to 30 +/- 2 torr within 1 min of injection of 0.01 microgram PAF and did not change (39 +/- 2 versus 40 +/- 2 torr) 1 min after 0.25% albumin (vehicle). Total pulmonary resistance was 0.18 +/- 0.04 torr/ml/min in normoxic rats and 0.19 +/- 0.04 and 0.28 +/- 0.06 torr/ml/min, respectively, in hypoxic rats receiving 0.01 microgram PAF or vehicle. The PAF (10(-10) to 10(-8) g/ml) also reversed hypoxic vasoconstriction in isolated lungs perfused at constant flow. Lungs perfused with salt solution but not those with blood became rapidly densensitized to PAF induced vasodilation. After constriction with 10(-6) M norepinephrine, both acetylcholine (10(-7) to 10(-6) M) and PAF (10(-10) to 10(-9) g/ml) dilated intact but not endothelium-denuded pulmonary artery rings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094418 TI - Rearrangement in the breakpoint cluster region and the clinical course in Philadelphia-negative chronic myelogenous leukemia. AB - We have followed one patient with Philadelphia (Ph)-negative chronic myelogenous leukemia and identified an additional four patients from the literature who showed the rearrangement in the breakpoint cluster region (bcr) on chromosome 22 characteristic of Ph-positive chronic myelogenous leukemia. The clinical course of these five patients was similar to that of Ph-positive patients, with easily controlled leukocyte counts, a prolonged benign phase, and prolonged survival. Furthermore, we have shown, for the first time, that bcr rearrangement in Ph negative chronic myelogenous leukemia can result in expression of the aberrant 210-kilodalton bcr-abl fusion protein, which has been strongly implicated in Ph positive leukemogenesis. Research data pertaining to possible cytogenetic mechanisms leading to production of p210bcr-abl in the absence of the Ph chromosome are reviewed. Molecular analysis provides an important tool for classifying and predicting prognosis of some patients with Ph-negative chronic myelogenous leukemia. PMID- 3094420 TI - Late-stage African trypanosomiasis and eflornithine. PMID- 3094419 TI - Leukocytoclastic vasculitis in association with immunoglobulin A myeloma. PMID- 3094421 TI - Middle ear mucosa in rats and humans. AB - The purposes of the study were to review thoroughly the literature and summarize it in a standardized fashion; to study the mucosa, including the distribution of mast cells, in all parts of the middle ear cavity in rats; and to compare the experimental findings with those known in humans. Adult, healthy rats were studied by light, scanning electron, and transmission electron microscopic techniques. The ciliated and secretory cells of the rat tympanic cavity are confined to two tracts, one anterior and one inferoposterior to the promontory. The tracts connect the epitympanum with the eustachian tube. The pars flaccida exhibits the highest density of mast cells, but mast cells are also distributed in the subepithelial layer of the tracts and in the floor of the tympanic bulla. The structure of the rat mucosa shows striking similarities to that of humans. Thus, from a morphological point of view, the rat seems to be a suitable model for middle ear studies. However, to be able to compare results obtained in different species and/or different laboratories, the areas of the middle ear from which the specimens have been taken must be carefully defined and presented in a standardized manner. PMID- 3094422 TI - [Value of pristinamycin (Pyostacine) in open fractures of the limbs]. PMID- 3094423 TI - The measurement of insulin-like growth factor I: clinical applications and significance. AB - Of the somatomedins so far measured, the selective quantitation of insulin-like growth factor I (IGF-I) appears to have the greatest potential in clinical diagnosis. There have been two approaches to the development of immunoassay systems. One type uses antibodies raised against synthetic fragments of IGF-I which exhibit cross-reactivity with the whole hormone. Such assay systems may be adequate for measuring normal adult plasma IGF-I levels, but the potential for the higher sensitivity required for detecting sub-normal plasma levels in young children is apparent only in methods using antibodies raised against the complete hormone. IGF-I in plasma exists as part of a high molecular weight complex in which it is bound to carrier proteins. The binding proteins may interfere with plasma IGF-I measurements by radioligand assays. Direct analysis of untreated plasma samples is claimed to be possible using disequilibrium assay conditions but in order to maximise assay sensitivity it is necessary to employ an initial extraction stage in order to eliminate binding protein interference. Whether the measurement of plasma IGF-I can or should be used in addition to, or as a replacement for, plasma growth hormone (GH) measurement in the clinical assessment of growth disorders remains a controversial issue. Available evidence indicates that a single, random plasma IGF-I level provides an accurate reflection of GH secretion. Adequate discrimination between the elevated levels in acromegaly and normal reference values has been demonstrated. However, in the investigation of growth-retarded children available radioimmunoassay (RIA) methods have proved only partially successful because of the age-related nature of normal plasma IGF-I concentrations. Existing assays appear capable of identifying sub-normal plasma levels after the age of approximately 4 years. In younger subjects an improvement in assay sensitivity is required in order to establish with greater accuracy the relevant normal ranges. Improvements in the identification of the particular lesion responsible for retarded growth in a child can be achieved by measurement of both plasma GH and IGF-I concentrations. The predictive value of the acute plasma IGF-I response to single-dose GH therapy may identify patients who will respond to long-term GH therapy. Better, more informed decisions on subsequent treatment may therefore be made. Apart from GH control, several other factors influence circulating IGF-I levels. Nutritional status can be assessed through reference to IGF-I analysis, overall catabolic or anabolic processes being associated with decreasing or increasing plasma IGF-I levels respectively. PMID- 3094424 TI - [Demonstration of a TRH precursor in the pancreas of the newborn rat]. AB - This study allows the indirect demonstration of a precursor for TRH in pancreatic extracts of 2-days old rats. The sequential treatment of these extracts with trypsin and carboxypeptidase A is followed by a large increase in Pyroglutamyl Histidine Proline (TRH-OH). The molecular weight of the protein that gives rise to TRH-OH after enzymatic treatment ranges between 30,000 and 40,000 daltons. During ontogenesis. TRH levels decrease earlier and more rapidly than that of TRH precursor levels. These data suggest that changes in the processing of TRH precursor play a role in the diminution of TRH concentrations that is observed during the first two weeks of life. PMID- 3094425 TI - [Role of calcium in TRH-induced secretion of alpha-MSH in the frog]. AB - In amphibians, alpha-MSH secretion is stimulated by thyrotropin-releasing hormone (TRH). In the present study we show that extracellular calcium influences directly the spontaneous secretion of alpha-MSH and that it participates in the mechanism of action of TRH on frog melanotrophs. PMID- 3094426 TI - [Phosphorylation of cytoplasmic proteins related to the multihormonal regulation of anterior pituitary cells]. AB - Thyrotropin releasing hormone (TRH) stimulates the synthesis and release of prolactin in mammotropic cells of the anterior pituitary and in GH4C1 cells. TRH simultaneously enhances the phosphorylation of a small number of proteins revealed in GH4C1 cells by two dimensional gel electrophoresis. The same phosphoproteins could be detected in normal rat pituitary cells in primary culture and were phosphorylated with the same pharmacology as in GH4C1 cells. Moreover, these proteins may also be related to hormonal regulations of the other cell types of the anterior pituitary. PMID- 3094427 TI - Moral foundation of nursing. PMID- 3094428 TI - Research testing nursing theory: state of the art. AB - The degree to which investigators have tested nursing theory through empirical research is analyzed. The analysis is based on 62 studies in which the nursing model of Johnson, Roy, Orem, Rogers, and/or Newman was used as a framework for the research. The analysis shows that of these 62 studies, only nine met specified evaluation criteria for the explicit testing of nursing theory. To better understand this finding, impediments and approaches to testing of nursing theory are discussed, as well as implications for nursing theory, research, and practice. PMID- 3094429 TI - Perceived situational control and perceived duration of time: expressions of life patterns. AB - Margaret Newman's model of perceived duration of time as an index to consciousness provided the theoretical framework for the study in which perceived control was tested as a possible factor in conflicting findings regarding perceived duration of time among the elderly. Forty institutionalized aged women were tested to explore the relationship between perceived control, age, and perceived duration of time as calculated into a consciousness index. Perceived duration of time was not found to be significantly related to age or perceived control. Length of institutionalization was positively related to perceived control. PMID- 3094431 TI - Theoretical and measurement issues in the study of field phenomena. AB - A correlational design was used to explore relationships among indicators of the human field and self-actualization in healthy women (N = 130). Perceived body size (PBS) indicated the size of the energy field; conversational distance (CD) indicated field density; and body weight indicated field pattern. The findings revealed an inverse correlation between self-actualization and CD as hypothesized. The negative correlation between the size of the field and density was in the expected direction but did not achieve significance. Body weight was related to CD but not in the expected direction. There was no relationship between body weight and PBS. PMID- 3094432 TI - The interaction model of client health behavior: application to the study of community-based elders. AB - The Interaction Model of Client Health Behavior (IMCHB) was used to direct a systematic and comprehensive description of community-based elders. The abstract concepts, constructs, factors, and variables described by one element of the model were able to account for 54% of the variance in elders' health status and 47% of the variance in their well-being. The model, as operationalized in this study, pointed to clear demographic, social, and health profiles that identified the elder at risk for decreased health, well-being, and self-care potential. The IMCHB would appear to be a useful framework with which to establish an empirical base on which nursing interventions could be developed. PMID- 3094433 TI - An empirical test of Maslow's theory of need hierarchy using hologeistic comparison by statistical sampling. AB - Maslow's hierarchy of basic human needs provides a major theoretical framework in nursing science. The purpose of this study was to empirically test Maslow's need theory, specifically at the levels of physiological and security needs, using a hologeistic comparative method. Thirty cultures taken from the 60 cultural units in the Health Relations Area Files (HRAF) Probability Sample were found to have data available for examining hypotheses about thermoregulatory (physiological) and protective (security) behaviors practiced prior to sleep onset. The findings demonstrate there is initial worldwide empirical evidence to support Maslow's need hierarchy. PMID- 3094430 TI - Human-environment process: a test of Rogers' principle of integrality. AB - Rogers' principle of integrality was examined through testing the hypothesis that healthy subjects who are confined to bed in a varied harmonic environment will perceive themselves to be more rested than those subjects confined to bed in quiet ambient environment. A two-group pretest-posttest design was used to gather data to test the hypothesis. The findings of the study revealed that the hypothesis was supported beyond the 0.05 level of significance. The integrity of the mutual human-environment field process was strengthened with an environment of varied harmonic sounds. PMID- 3094434 TI - Psychosocial theories of aging: a critical evaluation. AB - Three major psychosocial theories of aging--activity theory, disengagement theory, and continuity theory--are summarized and evaluated. Some important problems are identified with each of the theories when the criteria of intersubjectivity of meaning, testability, and empirical adequacy are utilized in the evaluation process. An analysis of relevant research shows that none of these three theories is clearly supported by empirical evidence. Because of the tentative nature and lack of conclusive support for each of these theories, further exploration and theory development is needed. It is suggested here that a phenomenological approach may be a more productive way to study the psychosocial aspects of aging. PMID- 3094436 TI - [Various ways of standardizing and unifying biological methods of determining the activity of antibiotics]. AB - It was shown possible to use nutrient media containing only salt components and agar-agar for determination of biological activity of tetracyclines (tetracycline, morphocycline, oxytetracycline and chlortetracycline), erythromycin and oleandomycin. A uniform nutrient medium containing ammonium chloride, trisubstituted sodium citrate, disubstituted sodium phosphate and agar agar was developed. Glucose is added to this medium simultaneously with the test microbe, B. subtilis ATCC 6633. The medium of the above composition provided readily reproducible results. PMID- 3094435 TI - [Oil and fat metabolism and the biosynthesis of penicillin]. AB - When grown on media with vegetable oils the producer of penicillin was more sensitive to changes in the conditions of mass transfer. Their worsening resulted in a more significant decrease in the level of the mycelium productivity than that of media containing animal fats. The observed differences were associated with the fact that the rate of consumption of readily assimilated fat substrates, for instance sunflower oil, by the cells was sufficiently high even at defective aeration and agitation. Their further oxidation in the mycelium was retarded which resulted in increasing lipid levels in the cells, irreversible destruction of the mitochondria, followed by further lowering of the oxidation processes in the cells, and inhibition of basic and secondary metabolism. On media containing whale oil there were also changes in the structure of the hyphae and first of all mitochondria of Penicillium chrysogenum and inhibited oxidation of fats evident from fractional composition of the mycelium lipids. However, all these changes were less pronounced because of the low rate of the whale oil assimilation by the cells. PMID- 3094437 TI - Rate of bactericidal activity for Streptococcus faecalis of a new quinolone, CI 934, compared with that of amoxicillin. AB - The rate of bactericidal activity of a new quinolone, CI-934, was compared with that of amoxicillin for 20 strains of Streptococcus faecalis. At 10 and 100 micrograms/ml, the bactericidal activity of CI-934 was more rapid at 6 h than that of amoxicillin. A paradoxical effect (a killing rate higher at 1 microgram/ml than at 100 micrograms/ml at 6 h) was observed for 19 of the 20 strains with amoxicillin and for 1 of the 20 strains with CI-934. It remains to be demonstrated whether in vivo studies will confirm the results obtained in vitro. PMID- 3094438 TI - Pharmacokinetics and pharmacodynamics of ciprofloxacin in cystic fibrosis patients. AB - The pharmacokinetics and blister fluid penetration of oral ciprofloxacin were compared in 11 cystic fibrosis (CF) patients who had sputum colonization but were asymptomatic and in 12 healthy volunteers after a single dose (500 mg) and at steady state (500 mg every 8 h). The antibacterial effect of ciprofloxacin therapy was also evaluated by bacterial counts of colonizing pathogens in the respiratory secretions of CF patients. The CF patients were 15.9% lighter in weight than the controls (P less than 0.05). After a single dose, the elimination half-life of ciprofloxacin was decreased by a third in the CF patients as compared with the controls (2.62 versus 3.93 h, respectively; P less than 0.01). This was the result of a diminished apparent volume of distribution in CF subjects. Interestingly, we observed no statistically significant difference in total apparent and renal clearances between the groups. Suction-induced blister fluid penetration was not different between CF patients and healthy volunteers. In CF patients, ciprofloxacin exhibited levels in respiratory secretions above the reported MIC for Pseudomonas aeruginosa: 1.36 and 1.86 micrograms/ml at 2 h after a single dose and at steady state, respectively. An important fall (mean, 3.9 log10/ml) in the log titer in 10 patients with P. aeruginosa in their respiratory secretions was observed after 5 days of treatment. However, this improvement was short-lived; the secondary increase in bacterial counts observed in five patients and the development of five resistant strains were causes for concern. The pharmacokinetic results presented here showed that ciprofloxacin should be administered every 8 or even every 6 h in CF patients. PMID- 3094439 TI - Comparative trial of single-dose ciprofloxacin and ampicillin plus probenecid for treatment of gonococcal urethritis in men. AB - In a double-blind comparative trial, 100 men with uncomplicated gonorrhea caused by beta-lactamase-negative Neisseria gonorrhoeae were treated with a single 0.25 g dose of ciprofloxacin administered orally or with 3.5 g of ampicillin plus 1.0 g of probenecid administered orally. Urethral infection was eradicated in all 49 men treated with ciprofloxacin and in 47 (92%) of 51 men treated with ampicillin probenecid (P = 0.12). The geometric mean MICs for pretreatment isolates were 0.008 microgram of ciprofloxacin per ml, 0.09 microgram of penicillin G per ml, 0.52 microgram of tetracycline per ml, and 23.5 micrograms of spectinomycin per ml. Chlamydia trachomatis infection persisted in 10 of 11 men treated with ciprofloxacin and in 11 of 14 men treated with ampicillin-probenecid. A single 0.25-g dose of ciprofloxacin was effective for treatment of uncomplicated urethral gonorrhea in men, but it did not eradicate coinfection with C. trachomatis. PMID- 3094440 TI - Effect of liposome-entrapped ampicillin on survival of Listeria monocytogenes in murine peritoneal macrophages. AB - The effect of liposomal encapsulation of ampicillin on the antibacterial activity against intracellular Listeria monocytogenes was studied by comparing survival of L. monocytogenes within peritoneal mouse macrophages in the presence of free ampicillin alone or in combination with liposome-entrapped ampicillin. In the presence of 50 micrograms of free ampicillin per ml of the incubation medium, intracellular growth of L. monocytogenes was still observed, although less as compared with intracellular growth in the absence of ampicillin. At a concentration of 50 micrograms of free ampicillin plus 100 micrograms of liposome entrapped ampicillin per ml, 99% of the intracellular bacteria were killed. On the other hand, a concentration of 150 micrograms of free ampicillin per ml plus empty liposomes only inhibited intracellular bacterial growth, and the bacteria were not killed. In addition, empty liposomes at a concentration of 1 mumol of lipid per ml had no effect on intracellular bacterial growth. In broth, liposome entrapped ampicillin at a concentration of 100 micrograms/ml was not bactericidal for L. monocytogenes, indicating that significant leakage of ampicillin from the liposomes with subsequent killing of the bacteria by the free drug did not occur. Therefore, we concluded that liposomal encapsulation of ampicillin results in an increased availability of the antibiotic for the intracellular bacteria. PMID- 3094441 TI - Pharmacokinetics of a new quinolone, AM-833, in mice, rats, rabbits, dogs, and monkeys. AB - The pharmacokinetics of AM-833 [6,8-difluoro-1-(2-fluoroethyl)-1, 4-dihydro-7-(4 methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid] were studied in mice, rats, rabbits, dogs, and monkeys by reversed-phase high-performance liquid chromatography. AM-833 was rapidly and completely absorbed from the digestive tracts of mice, rats, and dogs. About half of AM-833 bound to rat and dog serum proteins. Drug levels in lung, spleen, liver, and kidney tissues of rats and dogs were greater than the respective levels in serum but lower in brain tissue. Drug levels in tissues declined with the decrease in levels in serum. AM-833 penetrated rapidly and well into inflammatory exudate of rats. Elimination half lives in serum were species dependent, ranging from 1.57 h in rabbits to 9.42 h in dogs. Profiles of drug levels in serum were dose related over a single dose range from 2 to 40 mg/kg and not modified significantly during multiple dosing in dogs. Unchanged AM-833 was excreted in urine and bile in both rats and dogs. The metabolism of AM-833 was suggested by evidence that 24-h total recovery of unchanged AM-833 in urine and bile accounted for about half of the intravenous dose in rats. PMID- 3094442 TI - Aztreonam in the treatment of severe urinary tract infections in pediatric patients. AB - Aztreonam was administered to 30 patients, ages 0.03 to 15.4 years, with severe and in 21 cases complicated urinary tract infections caused by members of the family Enterobacteriaceae and Pseudomonas aeruginosa which were resistant to ampicillin and susceptible to the study drug in vitro. A mean dose of 47.7 mg/kg was given intramuscularly every 12 h to 26 patients. In four patients with renal insufficiency, the dose was reduced according to pharmacokinetic data. Permanent urine sterilization and clinical cure were achieved in 22 patients, 13 of whom had urological malformations. In two patients with P. aeruginosa and Proteus mirabilis infections, the treatment failed. Another patient had an Escherichia coli reinfection 21 days after the end of therapy. Four patients with various urological abnormalities had gram-positive superinfections, and two patients had gram-negative superinfections during and at the end of therapy: all six had indwelling ureteric splints or pyelostomy as predisposing conditions. No adverse clinical effects were observed. Some transient and slight or moderate alterations were observed at the end of treatment: eosinophilia (nine cases), elevation of hepatic enzymes (eight cases), prolongation of prothrombin time (three cases), and neutropenia (one case). A pharmacokinetic study was performed in six patients with normal renal function and in seven patients with various degrees of renal insufficiency. The elimination half-life of the drug was inversely correlated with the glomerular filtration rate. At the dosage used, aztreonam proved effective for severe urinary tract infections caused by members of the family Enterobacteriaceae in pediatric patients. PMID- 3094443 TI - Comparative clinical efficacy of single oral doses of cefuroxime axetil and amoxicillin in uncomplicated gonococcal infections. AB - Cefuroxime axetil (1.5 g) was compared with amoxicillin (3 g), both given as a single oral dose combined with probenecid (1 g) for the treatment of uncomplicated gonorrhea. Of 60 evaluable patients receiving amoxicillin, 55 (91.7%) were cured, whereas 55 (96.5%) of the 57 patients receiving cefuroxime axetil were cured (P greater than 0.1). Both drugs were well tolerated. PMID- 3094445 TI - Regulation of interferon-beta activity by fibroblast cells. AB - Exogenously administered interferons are rapidly cleared from the body. Several pharmacological mechanisms have been implicated in this clearance; however, they do not entirely explain the different clearance rates of the interferons. Cultured cells were studied for their ability to regulate interferon levels in vitro. Preparations of MuIFN-alpha, MuIFN-beta, and MuIFN-gamma were exposed to cells in culture and monitored for any loss in titer. MuIFN-beta titers were found to be significantly reduced following exposure to mouse L-929 fibroblast cells. The reduction of MuIFN-beta activity appeared to be specific for fibroblasts, since the reduction occurred following exposure to L-cells and to mouse embryo fibroblasts, but not to mouse reticuloendothelial cells. Moreover, the ability of the mouse fibroblast cells to reduce MuIFN-beta titers was blocked if the cells were pre-treated with actinomycin D, suggesting that de novo RNA synthesis was required. The titers of IFN-alpha and IFN-gamma were not reduced following exposure to either fibroblast or reticuloendothelial cells. Thus, the reduction of interferon titer by fibroblasts was IFN-beta specific. Similarly, HuIFN-beta titers were reduced following exposure to human fibroblasts. The ability of fibroblast cells to reduce IFN-beta titers was also found to be species-specific, since human fibroblast cells reduced the titer of HuIFN-beta but not MuIFN-beta while murine fibroblasts reduced the titer of MuIFN-beta but not HuIFN-beta. These results suggest that IFN-beta-treated fibroblasts specifically regulate their response to IFN-beta by reducing the titer of the IFN beta activity. PMID- 3094444 TI - In vitro activity of Ro 23-6240, a new difluoroquinolone derivative, compared with that of other antimicrobial agents. AB - Ro 23-6240 is a new difluorinated quinolone antimicrobial agent. Its in vitro activity against a wide range of bacteria was compared with those of other quinolones and beta-lactams. Generally, members of the family Enterobacteriaceae were inhibited by low concentrations of Ro 23-6240 (MIC90 [MIC for 90% of isolates tested], less than or equal to 1 microgram/ml). Ninety percent of Staphylococcus aureus (including methicillin-resistant strains) and Neisseria gonorrhoeae isolates were inhibited by 0.5 microgram/ml. Pseudomonas aeruginosa (MIC90, 2 micrograms/ml) and Bacteroides fragilis (MIC90, 4 micrograms/ml) showed intermediate susceptibility, and Streptococcus pneumoniae (MIC90, 8 micrograms/ml) was less susceptible. Strains resistant to nalidixic acid were less susceptible to all the quinolones tested. The protein binding of Ro 23-6240 (5 micrograms/ml) was 27%. PMID- 3094446 TI - Antibiotic susceptibility of clinical isolates of Pseudomonas aeruginosa. AB - Three hundred and twenty two clinical isolates of Pseudomonas aeruginosa collected in Morelia, Mexico, were analyzed for in vitro susceptibility to five antibiotics by agar dilution tests. Antibiotic resistance was shown by 50% of total isolates. Frequencies of resistance were: streptomycin, 47%; gentamicin, 13%; tobramycin, 8%; and carbenicillin, 7%; no amikacin resistance was found. The more common resistance patterns were streptomycin, gentamicin-streptomycin, and tobramycin-gentamicin-streptomycin. Resistance to either tobramycin, gentamicin or carbenicillin was found mainly in pyocin type 10 isolates. The proportion of antibiotic resistant isolates ranged from 37 to 75% in four hospitals, and amounted 24% in three clinical laboratories. PMID- 3094447 TI - Alpha-amylase and glucoamylase production by Schwanniomyces castellii. AB - A chromogenic substrate (Cibachron blue-amylose), and soluble starch and maltose were used to characterize the amylolytic system from Schwanniomyces castellii 3754. The strain was able to produce inducible alpha-amylase (EC 3.2.1.1) and glucoamylase (EC 3.2.1.3) when grown on different C sources. The effect of the C source was slightly different for alpha-amylase and glucoamylase production. Melezitose, maltose and soluble starch enhanced both alpha-amylase and glucoamylase synthesis to nearly the same extent; amylose, trehalose and cellobiose particularly induced alpha-amylase synthesis. The optimal pH for the release of both amylases was 5.5-7.0; maximal alpha-amylase synthesis, on the other hand, was observed in the medium buffered at pH 6.0. The optimal pH for alpha-amylase and glucoamylase activity was in the range of 4.5-7.2 and 4.2-5.5, respectively. Temperatures allowing maximal activity were 45 degrees C for alpha amylase and 45-52 degrees C for glucoamylase; a rapid decline of both activities was observed just above these temperatures. PMID- 3094449 TI - Microcetus lappus gen. nov., sp. nov.: new species of ciliated protozoon from the bovine rumen. AB - A new species of small, ciliated protozoon, Microcetus lappus gen. nov., sp. nov., from the rumen of Norwegian Red cattle is described. M. lappus possesses a novel cytopharyngeal apparatus of two rod-shaped structures, one situated on the dorsal side of the buccal cavity and one on the ventral side, suggesting that it belongs to a previously undescribed taxon. PMID- 3094448 TI - Establishment of beta-hydroxy fatty acids as chemical marker molecules for bacterial endotoxin by gas chromatography-mass spectrometry. AB - Selected ion-monitoring gas chromatography-mass spectrometry was used for detection of beta-hydroxy fatty acids as an independent assay for the presence or absence of endotoxin in materials claimed to induce nonspecific activation of Limulus amoebocyte lysate. To this end, suspensions of gram-negative and positive bacteria, one fungal species, cerebrospinal fluid, and hollow-fiber hemodialyzer rinses were assayed for endotoxin by gas chromatography-mass spectrometry and the Limulus amoebocyte lysate assay. Good qualitative agreement was shown for both methods when suspensions of test organisms were assayed. Two false-negative results were obtained by gas chromatography-mass spectrometry assays of cerebrospinal fluid and were shown to be a result of insufficient endotoxin in the cerebrospinal fluid specimens for detection by gas chromatography-mass spectrometry. Hemodialyzer rinses were Limulus assay positive; however, no beta-hydroxy fatty acids were detected by gas chromatography-mass spectrometry. These data were compared with data obtained from USP rabbit pyrogen tests of the rinse materials (nonpyrogenic) and chemical characterization of the Limulus assay-reactive rinses, which showed the rinses to be cellulosic in nature. It is suggested that beta-hydroxy fatty acids, as assayed by selected ion-monitoring gas chromatography-mass spectrometry, be used as chemical marker molecules for the presence or absence of endotoxin in materials reported to cause nonspecific activation of Limulus amoebocyte lysate. PMID- 3094450 TI - Effect of organotins on fecal pollution indicator organisms. AB - Pure cultures of Escherichia coli and Streptococcus faecalis and environmental water samples were examined for the possibility that pollution involving organotin compounds could decrease the values for indicator organisms when standard methods were applied to the analysis of water samples. (CH3)2SnCl2 and (CH3)3SnCl decreased viable counts at about 10 to 100 mg of Sn liter-1 (8.4 X 10( 5) to 8.4 X 10(-4) mol of Sn liter-1), and tributyltin chloride was effective at about 0.1 to 1.0 mg of Sn liter-1 (8.4 X 10(-7) to 8.4 X 10(-6) mol of Sn liter 1. These concentrations, particularly for the methyltin compounds, are greater than the concentrations reported to date for these compounds in aquatic ecosystems. Thus, organotin compounds alone would not be likely to cause reductions in counts of indicator organisms measured by standard methods. However, it is suggested that, when combined with other environmental stressors or upon long exposure, organotins such as butyltins may contribute to the injury of indicator organisms. PMID- 3094451 TI - Conjugal plasmid transfer (pAM beta 1) in Lactobacillus plantarum. AB - The streptococcal plasmid pAM beta 1 (erythromycin resistance) was transferred via conjugation from Streptococcus faecalis to Lactobacillus plantarum and was transferred among L. plantarum strains. Streptococcus sanguis Challis was transformed with pAM beta 1 isolated from these transconjugants, and transformants harboring intact pAM beta 1 could conjugate the plasmid back to L. plantarum. PMID- 3094452 TI - Post-translational events in proteoglycan synthesis: kinetics of synthesis of chondroitin sulfate and oligosaccharides on the core protein. AB - Chondrocytes isolated from the Swarm rat chondrosarcoma were incubated in culture with [1-3H]glucose for 30 min to 8 h. Labeled proteoglycans were isolated, treated with borohydride under alkaline conditions, and the three complex sugar structures purified: N- and O-linked oligosaccharides and chondroitin sulfate chains. The amount of incorporated radioactivity into each component sugar was analyzed by HPLC after enzyme digestion and hydrolysis. The kinetic data for labeling of each sugar over the time course of the experiment were fit to first order rate equations and the half times (t1/2) to linear labeling were calculated. The t1/2 values were essentially the same, 5-8 min, for galactose in all three complex sugar structures and for chain glucuronic acid in chondroitin sulfate, while that for xylitol in chondroitin sulfate, 15.8 min, was significantly longer. Thus, oligosaccharide synthesis is concomitant with chondroitin sulfate chain synthesis; the addition of the chondroitin sulfate linkage galactose occurs at or nearly at the same time as chain elongation while the addition of linkage xylose residues to the core protein may precede chain synthesis by up to 8 min. Since the intracellular t1/2 of the core protein precursor for these cells is 45 to 90 min, the data strongly suggest that the addition of xylose is not completed to any significant extent while the polypeptide is still nascent or shortly after its release into the rough endoplasmic reticulum. It is proposed that the addition of xylose to the core protein precursor is a late endoplasmic reticulum or early Golgi event. The analytical data were consistent with the presence of ester phosphate on about 80% of the xylose residues of the newly synthesized proteoglycan. PMID- 3094453 TI - [Total parenteral nutrition and chemotherapy in cancer patients]. AB - A common problem in cancer patients is a significant degree of malnutrition which disturbs and the accomplishment of surgery, chemotherapy and radiotherapy. Most patients with advanced cancer who should be treated with intensive chemotherapy are unable to ingest, digest or absorb sufficiently quantities of food and many antineoplastic agents affect the function of the alimentary tract. Therefore, total parenteral nutrition is a suitable method of nutritional support in these patients. The intravenous administration of nutrients can improve and maintain not only the nutritional status, but also the cell-mediated immunity of patients, and an effective or large doses of agents can be given as a result of increased tolerance. These effects are expected to enhance the potential of tumor response to chemotherapy. At the present time, only a few trials such as pulse TPN and amino acid imbalance therapy have been tried, but a specific nutritional regimen based on the altered metabolism in tumor and host should be developed in future. PMID- 3094454 TI - [Comparison of continuous venous infusion of 5-FU and FT-207 under total parenteral nutrition]. AB - Yoshida sarcoma-bearing rats were continuously infused with 5-FU at a dose of 20 mg/kg/day, and FT-207 at a dose of 40 mg/kg/day, 100 mg/kg/day or 140 mg/kg/day under TPN. After 4 days, rats were sacrificed and the 5-FU and FT-207 concentrations in their organs were measured. The 5-FU level in the tumor was almost the same at when 5-FU was injected at 20 mg/kg/day and FT-207 at 140 mg/kg/day. This 5-FU level in the tumor was twice and four times higher than that of the group injected with FT-207 at 100 mg/kg/day and 40 mg/kg/day. The 5-FU level in the tumor in all four groups was almost twice as high as that in the stomach, intestine and kidney, 7-10 times higher than that in the liver, and 10 30 times higher than that in serum. The FT-207 levels in the alimentary tract, kidney, tumor and serum were almost the same. The conclusion of our preliminary research is that FT-207 is recommended for use in continuous infusion at 7 times the dose of 5-FU when injected under TPN. PMID- 3094455 TI - [In vitro effects of 5-FU on gynecologic malignant tumor cell lines]. AB - In order to conduct a fundamental investigation of the effect of UFT on malignant tumors, biological experiments were conducted. UFT, 300 mg/day, starting one week prior to surgery, was administered in 12 cases of ovarian carcinoma. During the operation, 5-FU concentrations in serum, tumor tissues and adjacent normal tissues were measured. The results were as follows: 0.009 +/- 0.005 micrograms/ml in serum; 0.157 +/- 0.214 micrograms/g in tumor tissues, and 0.042 +/- 0.028 micrograms/g in adjacent normal tissues. Based upon these values, the plating efficiency of cultured tumor cell lines was measured in the presence of 5-FU in vitro. With 5-FU concentrations of 0.01 micrograms/ml, no sign of restriction in plating efficiency was observed. Restriction was initially observed at 0.1 microgram/ml, and became more pronounced at 1.0 microgram/ml. Furthermore, experiments using a uterine cervical carcinoma cell line (SKG-3) indicated that restriction of the plating efficiency was enhanced, not only by the 5-FU concentration but also by lapse of time. PMID- 3094456 TI - [The features of liver metastasis of breast cancer on imaging and its response to arterial infusion chemotherapy]. AB - Arterial infusion chemotherapy was performed in 21 patients with liver metastasis of breast cancer, which was suspected to be the limiting factor of the prognosis, and the relationship between the morphological types of liver metastases, percentage of the liver involved, their angiographic features and chemotherapeutic response was discussed. Four morphological types of liver metastases could be classified; solitary mass type, multiple nodular type, diffuse small nodular type, and mixed type. In most cases, metastatic lesions were detected as a hypoechoic area on US and as a low-density area on pre enhanced CT scan. In their angiographic features, these lesions were revealed as hypervascular tumors in most cases. Enlargement of the common or proper hepatic artery and obstruction of the 1st or 2nd branch of the portal vein were seen in over 50% of cases. In 13 evaluable cases, the response rate was 84.6% (PR 11, NC 1, PD 1), and the 50% survival time was 13.5 months in responders and 11.0 months for all cases. With regard to the morphological type, 1, 2 and 4-type cases revealed partial response, but NC or PD cases belonged to morphological type 3. No relation between obstruction of the portal vein and the chemotherapeutic response was observed. Arterial infusion chemotherapy was thus shown to be an effective treatment for liver metastasis of breast cancer, but that the response to the treatment differed for each morphological type. PMID- 3094458 TI - [Serum and tissue concentrations of UFT in patients with lung cancer]. AB - Postoperative serum and tissue concentrations of 5-FU, FT-207 and uracil were measured in 36 patients with lung cancer who were administered UFT for seven days preoperatively. The concentration of 5-FU was high in tumor tissue and lymph nodes, but very low in serum. Such differences were not observed in the FT-207 levels. Tumor concentration of 5-FU in patients administered daily doses of 600 mg was 0.151 +/- 0.099 microgram/g which was three times higher than the minimum inhibitory concentration, and higher than that seen with other doses. The histological type and T factor were not related to the tissue concentration of 5 FU. Lymph node metastasis was not related to the concentration of 5-FU in the lymph nodes. The optimal daily dose of UFT for patients with lung cancer was considered to be 600 mg. PMID- 3094457 TI - [Combined therapy of polyamine antimetabolite and nitrosourea in human gastric cancer]. AB - Antitumor therapy using the polyamine antimetabolites, alpha difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), combined with ACNU was studied in human gastric cancer xenotransplanted into nude mice. DFMO 1,000 mg/kg (in two divided doses) and MGBG 50 mg/kg were given i.p. for 6 successive days from the time when the xenotransplanted tumor weighed about 100 mg, and ACNU 20 mg/kg was given i.p. every other day from the same time. Antitumor efficacy was assessed by the time course of tumor weight as well as of DNA biosynthesis and polyamine levels in tumor tissue. Tumor weight was estimated using Battelle's Columbus Institute protocol and DNA biosynthesis was assayed biochemically by 3H-TdR injection at a prescribed interval after termination of therapy. Furthermore, tumoral polyamine levels were assayed by HPLC. This three drug regimen showed a favorable antitumor effect, compared to those of the other two therapies with DFMO plus MGBG as well as ACNU only. These data suggest that this combined regimen may have a synergistic efficacy judging from the action mechanisms of these three drugs. PMID- 3094460 TI - [Metabolism of tegafur in partial hepatectomized rats]. PMID- 3094459 TI - [Adjuvant chemotherapy of colorectal cancer--results of prospective randomized trials]. AB - The group of research for colorectal cancer treatments-Kajitani-group (chief T. Kajitani) has carried out the co-operative study for the evaluation of adjuvant chemotherapy after curative resection of colorectal cancer. During the period 1975 and 1978, a series of 1,156 cases of cancer of colon and rectum were entered into the prospective randomized controlled study which consisted of three treatment programs. There included chemotherapy of 2 modes of regimen combining MMC with Tegaful and non adjuvant treatment as control. In colon cancer, adjuvant chemotherapy combining MMC with Tegaful was effective on the increasing of survival rates, especially significantly (p = 0.017) in the cases of Dukes B stage (85-88% vs 69.2% in survival rates of 8 year). In rectal cancer, systemic intravenous administration of MMC 4 mg, two times a week for immediately postoperative three weeks, combined with postoperatively prolonged oral administration of Tegaful 800 mg/day more than three months was also significantly effective, especially in the cases of Dukes C stage (52.3% vs 40% in survival rates of 8 year). However, the analysis of recurrence did not prove that the intra-operative local intra vessel administration of MMC 10 mg was useful for the prevention of liver metastasis in colon cancer or pelvic recurrence in rectal cancer respectively. PMID- 3094461 TI - Neonatal intestinal lactase activity. AB - The sequential changes in intestinal lactase activity of 40 neonates were measured indirectly from the differential uptake and excretion of lactose and the non-metabolisable disaccharide lactulose contained in formula feeds. A daily decline in urinary lactose:lactulose excretion ratios, reflecting a rise in intestinal lactase activity, followed formula feeding. Percentage decline was related directly to gestation: full term infants displayed a fivefold greater decline in lactosuria than infants with a gestation of 28 weeks during the first 10 days of milk feeding. The difference between lactose:lactulose ingestion and excretion ratios suggests that within five days of starting feeds intestinal hydrolysis of lactose exceeds 98% efficiency, even in very preterm infants. PMID- 3094462 TI - A pilot study of serum polychlorinated biphenyl levels in persons at high risk of exposure in residential and occupational environments. AB - A pilot study was conducted to determine whether persons at high risk of exposure to three waste sites in the area of Bloomington, Indiana, have abnormally elevated serum polychlorinated biphenyl (PCB) levels. In addition, we attempted to determine which environmental pathways might have contributed most to these exposures. First, a screening questionnaire survey of 995 individuals was conducted; on the basis of these data, 114 of the persons who had the greatest potential for exposure were selected for inclusion in this pilot exposure assessment study. People near these waste sites have higher average serum PCB levels, and a greater percentage have abnormally elevated serum PCB levels, compared with previously characterized populations in the United States. However, we could not distinguish specific pathways of exposure and uptake, with the exception of persons with occupational exposures and, possibly, among persons who reportedly salvaged metal from discarded electrical equipment. Exposures in this community require further evaluation. PMID- 3094463 TI - A three year follow up of patients allocated to placebo, or oral or injectable gold therapy for rheumatoid arthritis. AB - Ninety patients randomly allocated to receive auranofin, matching placebo, or sodium aurothiomalate have been followed up for three years. Inefficacy led to cessation of treatment in 14 patients receiving auranofin, 27 receiving placebo, and one receiving sodium aurothiomalate. Twenty seven of the patients receiving placebo were reallocated within the study and 16 continued therapy at three years. This group showed similar statistically significant improvement in clinical and laboratory parameters at one, two, and three years to those on an active drug from the outset. Patients who discontinued auranofin because of inefficacy were offered sodium aurothiomalate therapy--eight patients in this group completed three years of treatment on sodium aurothiomalate and showed significant improvement in some but not all parameters. A hand radiograph erosion score showed a deterioration in 80% of patients remaining on auranofin, 75% of those on sodium aurothiomalate, and 80% of the original placebo group who continued an active drug for three years. Although more patients discontinued auranofin over the study period because of inefficacy, no difference could be shown between the degree of improvement in the subgroup who remained on auranofin and those receiving sodium aurothiomalate. No disadvantage in outcome could be shown for patients originally assigned to placebo. PMID- 3094464 TI - Binding of sodium aurothiomalate to human serum albumin in vitro at physiological conditions. AB - The binding of aurothiomalate to human serum albumin was studied by equilibrium dialysis at 37 degrees C, pH 7.3-7.4, and ionic strength 0.15-0.16 mol/l. It was found that aurothiomalate was bound to albumin at one site with an apparent association constant K1 = 3.0 X 10(4) M-1 and at three or more sites with the sum of association constants of the order of 10(3) M-1. Valuable information of the aurothiomalate-albumin interaction was deduced from the observed changes of pH of the albumin solutions during dialysis. A conceivable binding mechanism consistent with the results might be that aurothiomalate binds as Au+ to the high affinity binding site by exchanging a H+ and that this site might be the sulphydryl group in cysteine34; and that aurothiomalate binds as monomeric anions to the lower affinity binding sites. PMID- 3094465 TI - The effect of acute discontinuation of total parenteral nutrition. AB - The present study was undertaken to assess the impact of acute discontinuation (AD) of total parenteral nutrition (TPN) on serum glucose, insulin, and glucagon levels and on the generation of symptomatic hypoglycemia. Fifty studies were performed in 48 patients. In none of the 30 studies of 1 hour duration nor in the 20 studies of 8 hours duration was there a single episode of symptomatic hypoglycemia. One patient had a glucose below normal (60 mg/dl) during the first hour after AD. Glucose and insulin concentrations were elevated at the start of TPN discontinuation but returned to normal values within 60 minutes and remained there during the successive 7 hours of study. Although glucagon levels were slightly elevated at zero time, no significant decrease occurred. There was no evidence for counter-regulation based on the patterns of glucose and hormone levels. With some restrictions, acute discontinuation is a safe, rapid method of ending a prolonged TPN infusion. PMID- 3094466 TI - Impact of emergency angiography in massive lower gastrointestinal bleeding. AB - Fifty patients with massive lower gastrointestinal bleeding were initially managed with emergency angiography. The average age was 67.2; mean hematocrit, 23.7; and average transfusion, 7.6 units. Thirty-six patients (72%) had bleeding site located; bleeding sites were distributed throughout the colon. Etiologies of bleeding included diverticular disease (19 patients) and arteriovenous malformations (15 patients). Twenty of 22 (91%) patients receiving selective intra-arterial vasopressin stopped bleeding; however, 50% rebled on cessation of vasopressin. Thirty-five of 50 (70%) patients underwent surgery, with 57% operated on electively after vasopressin therapy. Seventeen patients had segmental colectomy, with no rebleeding. Nine of the 17 patients had diverticular disease in the remaining colon. Operative morbidity in these 35 patients was significantly improved when compared to previously reported patients undergoing emergency subtotal colectomy without angiography (8.6% vs. 37%) (p less than 0.02). Emergency angiography successfully locates the bleeding site, allowing for segmental colectomy. Vasopressin infusion transiently halts bleeding, permitting elective surgery in many instances. PMID- 3094468 TI - Does preoperative percutaneous biliary drainage reduce operative risk or increase hospital cost? PMID- 3094467 TI - Evidence for dual modulation of pepsinogen secretion using isoproterenol, carbachol, CCK-8, forskolin, 8 bromo-cAMP, and A23187 probes. AB - The cellular mechanisms by which pepsinogen (PNG) secretion is controlled are not understood. The aim of this study was to explore whether modulation of PNG secretion is mediated by cAMP or calcium-calmodulin (C-C). PNG secretion in isolated rabbit gastric fundic glands (IGG) was tested, using agents believed to act via cAMP or C-C. IGG were stimulated for 30 minutes with histamine (H) 10(-5) M, isoproterenol (I) 10(-5) M, carbachol (C) 10(-5) M, cholecystokinin octapeptide (CCK-8) 10(-7) M, forskolin (F) 10(-5) M, 8 bromo-cAMP (8B) 10(-3) M, and A23187 (A) 10(-6) M. PNG levels were determined by spectrophotometric assay of hemoglobin digestion products. PNG amounts secreted were (mean per cent above basal levels of total IGG PNG units +/- SEM): H, -0.02 +/- 0.30%; I, 3.5 +/- 0.9%; C, 5.1 +/- 2.2%; CCK-8, 5.3 +/- 1.5%; F, 10.6 +/- 3.8%; 8B, 13.8 +/- 4.5%; A, 2.1 +/- 1.1%. All secretagogues except H stimulated PNG release significantly above basal levels (p less than 0.05). A primary histaminergic mechanism for pepsinogen secretion is unlikely. Since two other adenylate cyclase activators, isoproterenol and forskolin and the 3':5'-cyclic adenosine monophosphate analog 8 bromo cAMP stimulated pepsinogen secretion, cAMP-dependence is probable. Since carbachol, CCK-8, and A23187, which are believed to act via calcium-calmodulin, also stimulated pepsinogen secretion, this system, too, presumably plays a substantial role. Thus the data support a dual 3':5'-cyclic adenosine monophosphate/calcium-calmodulin modulation of pepsinogen secretion. PMID- 3094469 TI - Branched chain amino acid enriched solutions in the septic patient. PMID- 3094470 TI - Behavioral effects of lithium on presynaptic sites of catecholaminergic neurons in the mouse. AB - The effect of lithium on locomotor activity in mice was studied and an attempt was made to elucidate the neuronal mechanisms involved. Lithium chloride (200 mg/kg, i.p.) administered acutely or daily for 7 days did not affect locomotor activity. A single injection of apomorphine at a low dose of 0.25 mg/kg (i.p.) markedly decreased locomotor activity but repeated injection of the drug produced hyperlocomotion accompanied by sniffing. Methamphetamine (1 mg/kg, i.p.), haloperidol (0.02 mg/kg, i.p.), thyrotropin releasing hormone (5 mg/kg, i.p.) or apomorphine (1 mg/kg, i.p.) exerted a biphasic action in locomotor activity, i.e. an initial increase and subsequent decrease. This initial hyperlocomotion induced by these drugs, except for apomorphine, was inhibited by lithium (200 mg/kg, i.p. X 1) or a low dose of apomorphine (0.25 mg/kg, i.p. X 1). The subsequent hypolocomotion was also attenuated by lithium, but not by apomorphine. Imipramine (10 mg/kg, i.p.) increased the hyperlocomotion induced by methamphetamine. The inhibitory effect of tetrabenazine (5 mg/kg, i.p.) on locomotor activity was attenuated after repeated treatment with lithium (200 mg/kg, i.p. X 7) or imipramine (10 mg/kg, i.p. X 7). The results suggest that lithium may inhibit dopaminergic neuron activities, probably not through an activation of presynaptic dopamine autoreceptors. PMID- 3094471 TI - Nitroglycerin patches a handicap? PMID- 3094472 TI - Production, by filamentous, nitrogen-fixing cyanobacteria, of a bacteriocin and of other antibiotics that kill related strains. AB - Colonies of sixty-five filamentous cyanobacteria were screened for the production of temperate phages and/or antibiotics on solid medium. None of them was observed to release phages. However, seven N2-fixing strains were found to produce antibiotics very active against other cyanobacteria. The antibiotic produced by Nostoc sp. 78-11A-E represents a bacteriocin of low molecular weight. Nostoc sp. ATCC 29132 appears to secrete, together with an antibiotic, a protein that inhibits its action. PMID- 3094473 TI - Isolation of cyanobacterial heterocysts with high and sustained dinitrogen fixation capacity supported by endogenous reductants. AB - A method is described for the preparation of cyanobacterial heterocysts with high nitrogen-fixation (acetylene-reduction) activity supported by endogenous reductants. The starting material was Anabaena variabilis ATCC 29413 grown in the light in the presence of fructose. Heterocysts produced from such cyanobacteria were more active than those from photoautotrophically-grown A. variabilis, presumably because higher reserves of carbohydrate were stored within the heterocysts. It proved important to avoid subjecting the cyanobacteria to low temperatures under aerobic conditions, as inhibition of respiration appeared to lead to inactivation of nitrogenase. Low temperatures were not harmful in the absence of O2. A number of potential osmoregulators at various concentrations were tested for use in heterocyst isolation. The optimal concentration (0.2 M sucrose) proved to be a compromise between adequate osmotic protection for isolated heterocysts and avoidance of inhibition of nitrogenase by high osmotic strength. Isolated heterocysts without added reductants such as H2 had about half the nitrogen-fixation activity expected on the basis of intact filaments. H2 did not increase the rate of acetylene reduction, suggesting that the supply of reductant from heterocyst metabolism did not limit nitrogen fixation under these conditions. Such heterocysts had linear rates of acetylene reduction for at least 2 h, and retained their full potential for at least 12 h when stored at 0 degree C under N2. PMID- 3094474 TI - [Quantitative bacteriologic studies on experimentally infected laboratory animals. 3. Dynamics of germ counts in mice experimentally infected with Listeria monocytogenes]. PMID- 3094475 TI - Blood gas changes and hypophosphatemia in lactate-induced panic. AB - Alkalosis is prominent among the many physiologic and biochemical effects of sodium lactate infusion. Though this is partially due to the conversion of lactate to bicarbonate, the metabolic component, it may also be secondary to hyperventilation before and during the infusion, the respiratory component. We analyzed pH, carbon dioxide pressure, bicarbonate, and inorganic phosphate from patients with panic disorder and agoraphobia with panic attacks and from normal controls both before and during lactate infusion. Our findings extend earlier work demonstrating that many such patients are chronic hyperventilators. Both metabolic and respiratory alkalosis develop in all subjects during lactate infusion, but only hyperventilation-induced hypocapnia differentiates patients at the point of lactate-induced panic from nonpanicking patients and normal controls. Finally, low inorganic phosphate levels at baseline appear associated with patients who will panic during the subsequent lactate infusion. This last unexpected finding may reflect hyperventilation or an abnormality in intracellular glycolysis. PMID- 3094477 TI - Juvenile xanthogranuloma. Ultrastructural and immunocytochemical studies. AB - Morphologic features of three cases of juvenile xanthogranuloma (JXG) were consistent with the current concept of a benign process, although the lesion in one case grew steadily to an extensively infiltrating large mass, which clinically suggested a malignant growth. Ultrastructurally, the lesion consisted of morphologically different developmental stages of histiocytes, probably reflecting different functional levels. An interesting finding was the presence of occasional subplasmalemmal linear densities between these cells. These densities were at times symmetrically opposed, forming desmosomelike junctional complexes. Immunohistochemical study for the presence of lysozyme, alpha 1 antitrypsin, and S100 protein by the avidin-biotin-peroxidase complex was performed in all three cases. All immunostains were negative except the positive lysozyme stain in two cases. The ultrastructural and cytochemical characteristics of histiocytes in JXG were similar to epithelioid cells in the lymph node, suggesting that JXG is a reactive lesion. PMID- 3094476 TI - Gamma-chain heavy-chain disease with primary thyroid plasmacytoma. AB - A case of gamma-chain heavy-chain disease was associated with primary thyroid plasmacytoma. The patient has been free of complaints for two years since the removal of the tumorous thyroid. The heavy-chain fragment (molecular weight, 32,000 daltons) has disappeared from the serum and urine, while the previously low levels of normal immunoglobulins have increased. The immunoglobulin anomaly may be correlated with the chronic antigen stimulus. PMID- 3094478 TI - Cost-effectiveness of the Medicare three-hour regulation. AB - In September 1982 Medicare instituted a requirement that patients in acute medical rehabilitation hospital units receive a minimum of three hours per day of physical and occupational therapy combined. To investigate the consequences of that policy functional status, charges and other outstanding measures of rehabilitative outcomes were assessed for 934 patients before and after implementation of the regulation. After the regulation, average daily intensity of physical plus occupational therapy increased 0.55 hours per patient day, adding charges of $408,000 over the sample. The increased intensity of therapy provided no detectable benefit to patients in terms of improved functional status, living arrangement, or other outcomes. Results underscored the importance of grading the intensity of rehabilitation to the varying needs of patients. PMID- 3094479 TI - Description of a continent jejunal gastrostomy. AB - A new technique of permanent gastrostomy interposes a vascularized jejunal conduit with an intussuscepted valve between the stomach and abdominal wall, creating a "continent jejunal gastrostomy". In a series of dogs undergoing gastrostomy, the continent jejunal gastrostomy functioned well, with no leakage, and was superior to gastric tube gastrostomy in this regard. Furthermore, there was no evidence of marginal ulceration. A patient who underwent continent jejunal gastrostomy has an excellent one-month result. PMID- 3094480 TI - Discharge within 24 hours of elective cholecystectomy. The first 100 patients. AB - Discharge with 24 hours of elective cholecystectomy has proved to be an attainable goal for the vast majority of patients, without increasing risk. The clinical courses of the first 100 subjects (of 109 consecutive patients) to reach this goal were examined critically. Preservation of gastrointestinal function and immediate full enteral nutrition were major steps toward reduction of hospital dependency. Pain and the need for narcotics were reduced by careful patient instruction and wound infiltration with a long-acting local anesthetic. Preoperative hospitalization was eliminated by outpatient testing and admission for 29 subjects, who were admitted the day of surgery. This group's entire stay was only one day. Patients and family found the total regimen acceptable by independent review. Significant cost savings were realized as a fringe benefit. PMID- 3094481 TI - Quantitation of corneal inflammation by chemiluminescense. AB - Various inflammatory agents, including Pseudomonas aeruginosa, bacterial filtrates, endotoxin, and phorbol myristate acetate were found to induce significant increases in corneal chemiluminescense (CLM). Disruption of polymorphonuclear leukocytes within corneas by sonication, freeze-thawing or cryotherapy, or reduction of corneal infiltration by induction of neutropenia resulted in marked decreases of CLM. Increased corneal CLM was associated with significant increases in corneal thickness and water content. Oxygen-free radical scavengers significantly inhibited CLM of experimentally infected corneas in vitro, as did the anti-inflammatory agents prednisolone acetate, indomethacin, and salicylic acid. In vivo therapy of infected corneas with prednisolone resulted in significant reductions in corneal CLM, thickness, and water content compared with saline-treated eyes. The CLM assay is a simple technique that allows quantitation of corneal inflammation and evaluation of the effect of therapeutic agents on corneal inflammation. PMID- 3094482 TI - [Effects of acetaldehyde on plasma free fatty acid in rabbits]. PMID- 3094483 TI - Sequential therapy with clomiphene citrate and human menopausal gonadotropin for induction of ovulation and pregnancy. PMID- 3094484 TI - Diagnosis-related groups, peer review and the evaluation of hospital activities. PMID- 3094485 TI - An experimental study and computer simulation of the turnover of choline in erythrocytes of patients treated with lithium carbonate. AB - The mechanism by which choline accumulates in erythrocytes during treatment with lithium salts has been elucidated. A component of the study was a kinetic description of erythrocyte phospholipase-D, which catalyses the release of intracellular choline from phospholipids. Apparent steady-state kinetic parameters for calcium ions were determined: Km (+/- SD) = 0.6 +/- 0.3 mmol/l aqueous cell volume and Vmax (+/- SD) = 12 +/- 4 mumol/l packed red blood cells (RBC) min-1. Competitive inhibition of the phospholipase-D by barium ions was also observed. Other information concerning choline and lithium levels and red cell life-time was obtained from the literature. Details of the kinetics were used to develop a comprehensive dynamic model of choline metabolism by erythrocytes. The scheme is as follows; phosphatidylcholine associated with high density lipoproteins exchanges with the erythrocyte membrane phospholipids, the neutral phospholipids undergo two dimensional translational and rotational motion and also flip between each layer of the bilayer thus becoming exposed to an intracellularly-located phospholipase-D, whereupon the choline is hydrolysed and released into the intracellular milieu. A choline transport protein, which is able to be inhibited by lithium, mediates the influx and efflux of choline. The differential equations that describe reactant flux in this scheme were integrated numerically and the choline accumulation profiles under various conditions of transport and enzyme inhibition are presented. Computer solution of the model, by using as input values plasma lithium levels in the upper limit of the therapeutic range, required that the red cell life-time be reduced in order to explain the previously observed negative association between choline and increasing lithium levels. The results of the computer simulations under varying initial conditions of plasma and erythrocyte lithium and choline concentrations permit, for the first time, a comprehensive description of those factors affecting erythrocyte choline levels. PMID- 3094486 TI - Changes of serum histaminase activity in pollinosis. AB - In order to study changes in serum histaminolytic enzyme activity in allergic individuals following allergen challenge, serum histaminase activity was measured using the 0-dianisidine peroxidase method in patients with Japanese cedar pollinosis. Significantly higher serum histaminase activity was detected in pollen season than out of season and a significant relationship was recognized between serum histaminase activity and the severity of nasal symptoms. PMID- 3094487 TI - Determinations of glucose turnover and oxidation in normal volunteers and septic patients using stable and radio-isotopes: the response to glucose infusion and total parenteral feeding. AB - Rates of glucose turnover and oxidation were isotopically determined in normal volunteers (n = 16) and in severely septic patients (n = 10). Glucose turnover was determined using primed constant infusions of either 6-3H- or 6,6-d-glucose and glucose oxidation with either U-14C-glucose or U-13C-glucose after appropriate priming of the bicarbonate pool. Basal rates of glucose turnover, oxidation, and plasma clearance were significantly higher in the septic patients than in the volunteers. During glucose infusion (4 mg/kg.min) endogenous glucose production was virtually abolished in the volunteers (94 +/- 4% suppression). There was significantly less suppression in the septic patients (39 +/- 7%); (P less than 0.01). In addition, the percentage of available glucose oxidized (i.e. the percentage of glucose uptake oxidized) was significantly less in the septic patients. When the patients were studied during total parenteral nutrition (at a similar rate of glucose infusion) there was no further suppression of endogenous glucose production compared with that seen during 2 h of glucose infusion. However, the percentage of available glucose oxidized increased significantly. From these studies it is concluded that septic patients continue to have ongoing consumption of host tissue despite receiving either glucose infusion or total parenteral nutrition, and septic patients are less able to oxidize glucose than normal volunteers when infused for only 2 h. However, adaptation occurs with the longer infusion time used in total parenteral nutrition (TPN). PMID- 3094488 TI - Influence of age, sex, duration of symptoms and dehydration of serum electrolytes in hypertrophic pyloric stenosis. AB - A review was conducted of 234 consecutive patients with hypertrophic pyloric stenosis (HPS) proven at operation. The relationship of age, sex, the duration of symptoms and the clinical degree of dehydration to the severity of metabolic derangement as reflected by alterations in serum electrolytes and acid-base status, was analysed statistically. The length of history and the degree of dehydration was found to have predictive value in identifying those likely to have major metabolic disturbances. Where severe vomiting has persisted for more than 1 week, major derangements of the biochemical parameters should be anticipated; and where clinical assessment of dehydration is estimated as being greater than 5%, there is almost always some major biochemical abnormality present. Nevertheless, variation in individual cases necessitates that all patients with suspected HPS should have serum electrolytes and acid-base estimations performed. PMID- 3094489 TI - The relationship between the isolation of Brucella abortus and serological status of infected, non-vaccinated cattle. AB - Seventy two non-vaccinated cattle with various complement fixation (CF), rose bengal (RB) and enzyme-linked immunosorbent assay (ELISA) results at slaughter were examined bacteriologically and serologically. Brucella abortus was recovered from 49 (68.1%) of the cattle and the use of a biphasic culture medium was entirely responsible for the detection of 6 (12.2%) of the culture positive cattle. The supramammary and retropharyngeal lymph nodes were the most rewarding tissues to culture. A comparison of culture results and serological status demonstrated that B. abortus could be isolated from cattle with negative RB and CF tests and that the ELISA was useful in detecting these cattle and infected cattle with low CT titres. The RB test was also useful as it detected all but 4 of the cattle found to be infected. PMID- 3094490 TI - An improved microbiological assay for chlortetracycline in avian plasma. AB - Bacillus cereus was used as the assay organism for the quantification of chlortetracycline (CTC) in avian plasma. Antibiotic medium #8 gave significantly larger zones of inhibition than nutrient agar 1.5% when used as the assay medium (P less than or equal to 0.05). When the CTC concentration was measured in serum, citrated plasma, heparinized plasma, and oxalated plasma, no significant differences were found between the inhibition zone diameters produced on antibiotic medium #8. However, there was a significant decrease in the zone diameters produced on this medium when citrated whole blood, oxalated whole blood, and heparinized whole blood were used instead of plasma. The length of incubation of assay plates was inversely related to the inhibition zone diameter, with an incubation time of 8 hr giving the largest and most distinct zones. Storing prepared assay plates at 4 C for 24 hr before use appeared to decrease the variability of the inhibition zone diameters. Storage of citrated plasma at 4 C for 48 hr and at -60 C for 9 days resulted in no significant decreases in CTC concentrations. PMID- 3094491 TI - Heuristics, normative models, and the value of serial test patterns. AB - This paper deals with living systems at the level of the human organism, including all subsystems. It argues that, in medicine, conclusions about the adequacy of clinical heuristics, vis-a-vis normative models, may be suspect until the models are more adequately designed and the heuristics better defined. Through a theoretical analysis, it shows that dynamic information, ordinarily ignored in normative models yet often present in biological systems, can have a profound impact on the cost-effectiveness of test use. Empirically, it also shows that explicit clinical policies ignoring dynamic test patterns can lead to substantial loss in diagnostic information. These results motivate research on clinical strategies for using dynamic information. They also suggest unmet needs in evaluating tests, providing decision support, and educating physicians in cost effective test use. PMID- 3094492 TI - Isolation and identification of higher plant agents active in antimutagenic assay systems: Glycyrrhiza glabra. PMID- 3094493 TI - Nucleotide excision repair genes from the yeast Saccharomyces cerevisiae. AB - The genetics of nucleotide excision repair in the yeast Saccharomyces cerevisiae is complex, apparently requiring at least 10 genes. We have isolated 5 of these genes (designated RAD1, RAD2, RAD3, RAD4, and RAD10) by molecular cloning and plan to overexpress them in order to generate proteins for biochemical study. We have sequenced four of these five genes and have noted regions of homology with other proteins in the predicted amino acid sequence of some of them. In particular, there is striking homology between Rad3 protein and a number of prokaryotic and eukaryotic proteins that bind nucleotides and hydrolyze ATP or GTP. Mutations in this region of the RAD3 gene render cells defective in the nucleotide excision repair function. In addition to its role in nucleotide excision repair, the RAD3 gene is essential for the viability of haploid cells in the absence of DNA damage. The nature of the essential function is unknown. The RAD1 and RAD3 genes are not inducible by DNA damaging agents. However, exposure of cells to UV radiation, 4-nitroquinoline 1-oxide, or gamma radiation results in 4- to 6-fold enhanced expression of the RAD2 gene. PMID- 3094494 TI - Multiple inducible cytochromes P-450 in yeast. AB - A form of cytochrome P-450 is produced in Saccharomyces cerevisiae during the logarithmic growth phase. This form is inhibited by metyrapone, tetrahydrofuran, and carbon oxide which are inhibitors of ethanol-inducible cytochromes P-450 of mammals. Addition of Na-phenobarbital to the 0.5% glucose liquid medium induced a form of cytochrome P-450 inhibited only by metyrapone. Thus, yeast possess multiple forms of cytochrome P-450 that are individually inducible. PMID- 3094495 TI - Protective effects of beta-carotene against psoralen phototoxicity: relevance to protection against carcinogenesis. PMID- 3094496 TI - Cytochromes P-450 and the activation and inactivation of mutagens and carcinogens. PMID- 3094497 TI - [Blood gas analysis in cadaveric blood--initial results]. PMID- 3094498 TI - [Principles of nutritional requirements in artificial nutrition]. PMID- 3094499 TI - [Metabolic effect of intravenously administered glucose, xylose or glycerin in various dosages and combinations]. PMID- 3094500 TI - [Measuring absorption in the dog model: determination of portal vein assimilation of enterally administered substrates]. PMID- 3094501 TI - [Amino acid requirements of premature and newborn infants and young infants in enteral and parenteral nutrition. A critical presentation of the organized methodology and comparative evaluation of amino acid requirements]. PMID- 3094502 TI - [Carnitine in nutritional therapy]. PMID- 3094503 TI - [Hypocaloric parenteral feeding]. PMID- 3094504 TI - [Clinical studies of parenteral feeding using the peripheral veins. Effect of a 3.5 percent amino acid solution on postoperative metabolism with special reference to amino acid balance]. PMID- 3094505 TI - [Behavior of insulin, glucagon, cortisol and thyroid hormones in plasma in the early post-traumatic phase with and without modification by nutritional therapy adapted to metabolism]. PMID- 3094506 TI - Isolation of a cDNA coding for human galactosyltransferase. AB - Human milk galactosyltransferase (EC 2.4.1.22) was purified to homogeneity using affinity chromatography. Edman degradation was used to determine the amino acid sequences of eight peptide fragments isolated from the purified enzyme. A 60-mer "optimal" oligonucleotide probe that corresponded to the amino acid sequence of one of the galactosyltransferase peptide fragments was constructed and used to screen a lambda gt10 cDNA library. Two hybridization-positive recombinant phages, each with a 1.7 Kbp insert, were detected among 3 X 10(6) recombinant lambda gt10 phages. Sequencing of one of the cDNA inserts revealed a 783 bp galactosyltransferase coding sequence. The remainder of the sequence corresponded to the 3'-region of the mRNA downstream from the termination codon. PMID- 3094507 TI - Evidence for a Sertoli cell, FSH-suppressible inhibiting factor(s) of testicular steroidogenic activity. AB - By using a model of immature porcine Leydig and Sertoli cells cultured in serum free defined medium, we evidenced a paracrine control of Leydig cell steroidogenic activity by Sertoli cells via a secreted inhibiting protein(s). This protein(s), partially purified using gel filtration (M.W. 20,000-30,000) suppresses the steroidogenic responsiveness to LH/hCG by decreasing the specific LH/hCG binding (52% decrease) and hormone steroid biosynthesis (73% decrease) at a level(s) located between cAMP production and pregnenolone formation. The suppression of this inhibitor(s) by FSH, in a dose dependent manner, is one mechanism by which FSH "sensitizes" Leydig cell response to LH/hCG stimulation. PMID- 3094508 TI - Lack of correlation between TPA-induced prostaglandin biosynthesis and ornithine decarboxylase activity in Balb/c mouse 3T3 fibroblasts. AB - 12-O-tetradecanoylphorbol-13-acetate (TPA) induced in Balb/c 3T3 cells an earliest prostaglandin biosynthesis and an ornithine decarboxylase activation, this time-relation being more evident if serum was added to incubation medium in low concentration (0.2%). However the two TPA-induced events can be almost totally dissociated by pharmacological means, such as indomethacin and calcium ionophore A23187 which affected PG response to TPA, but did not influence ODC induction. PMID- 3094509 TI - Prenylated proteins from kidney. AB - When [5-3H]mevalonate is injected into mice, it is incorporated into macromolecules in the kidney. The incorporated material is stable to treatment with RNase or DNase but not protease, indicating that the radioactivity is associated with protein. Electrophoresis in sodium dodecyl sulfate-containing polyacrylamide gels indicates a molecular weight of about 25,000. The incorporated radioactivity can be released from the polypeptide and extracted into organic solvents after hydrolysis with acid or base or by treatment with protease. The conditions required for hydrolysis strongly suggest that the linkage between the protein and the mevalonate-derived material is an allylic ether. The chromatographic mobility of the incorporated material in several systems is similar to that of dolichol C95. PMID- 3094510 TI - Thrombin and ionomycin can raise platelet cytosolic Ca2+ to micromolar levels by discharge of internal Ca2+ stores: studies using fura-2. AB - In the presence of 1 mM EGTA, the addition of the calcium ionophore ionomycin to human platelets loaded with 30 microM fura-2 could elevate [Ca2+]i from less than 100 nM to a maximum of greater than 3 microM, presumably by discharge of Ca2+ from internal stores. Under the same conditions thrombin could maximally increase [Ca2+]i to a peak of greater than 1 microM which then declined to near resting levels within 3-4 minutes; by contrast in platelets loaded with 1 mM quin2 thrombin could raise [Ca2+]i to only about 200 nM. In the presence of 1 mM Ca2+ the peak response to thrombin in fura-2-loaded platelets was higher (1.4 microM) than that observed in the presence of EGTA (1.1 microM) and the elevation in [Ca2+] was prolonged, presumably by Ca2+ influx. These results with fura-2-loaded platelets indicate that mobilisation of internal Ca2+ can contribute a substantial proportion of the early peak [Ca2+]i evoked by thrombin directly confirming the deductions from previous work with different loadings of quin2. Under natural conditions the major role of Ca2+ influx may be to prolong the [Ca2+]i rise rather than to make it larger. PMID- 3094511 TI - Apolipoprotein E-mediated binding of hypertriglyceridemic very low density lipoproteins to isolated low density lipoprotein receptors detected by ligand blotting. AB - HTG-VLDL1, like LDL, bind with high affinity to electrophoretically transferred, isolated LDL receptors partially purified from bovine adrenal glands. Ligand blotting techniques show that binding is calcium dependent; little or no binding of LDL or HTG-VLDL1 is observed in the presence of 10 mM EDTA. HTG-VLDL1 does not bind in the presence of 7 mM suramin, an inhibitor of LDL binding to the LDL receptor. Pretreatment of LDL with either thrombin or trypsin does not affect apoB-mediated LDL binding to the LDL receptor. ApoE-mediated binding of HTG-VLDL1 to the blotted LDL receptor is abolished or greatly decreased by thrombin treatment of HTG-VLDL1; trypsin treatment of HTG-VLDL1 abolishes binding. Reincorporation of apoE into trypsinized HTG-VLDL1 restores binding. These studies demonstrate unequivocally that HTG-VLDL1 bind to the LDL receptor, that the binding of HTG-VLDL1 to the isolated LDL receptor is mediated through the thrombin-accessible apoE, and that HTG-VLDL1 which bind via potentially dissociable apoE rather than non-transferable apoB can be used for ligand blotting. PMID- 3094512 TI - The HTLV-III envelope protein contains a hexapeptide homologous to a region of interleukin-2 that binds to the interleukin-2 receptor. AB - A region of human interleukin-2 (IL-2) which was predicted to be a contact point with its receptor was used to locate a homologous region in the envelope protein of human T-lymphotropic retrovirus (HTLV-III). This homologous six amino acid peptide from the carboxy (C)-terminus of the HTLV-III envelope protein was found to inhibit the biological activity of human IL-2 in a murine spleen cell proliferation assay. When conjugated to a carrier protein, this peptide inhibited the binding of radiolabelled IL-2 to its receptor. The biological activity of the peptide was antagonized by a six amino acid peptide fragment of the IL-2 receptor which was predicted to be the contact point on the receptor that corresponded to the binding region of IL-2. The HTLV-III peptide also inhibited the binding of radiolabelled IL-2 to polyclonal anti-IL-2 antiserum. These data support the previous assignment of contact points between IL-2 and its receptor. They also suggest two possible mechanisms of immunosuppression during acquired immunodeficiency syndrome (AIDS). One involves direct competition of the envelope protein or its fragments with IL-2 for binding to the IL-2 receptor. The other involves antibodies to the envelope protein which crossreact with and neutralize IL-2. PMID- 3094513 TI - Crystalline serine hydroxymethyltransferase from an obligate methylotroph, Hyphomicrobium methylovorum. AB - Optimal culture conditions of a methylotrophic Hyphomicrobium methylovorum and improved purification of serine hydroxymethyltransferase from the bacterium were established for the large-scale preparation of the enzyme. The first crystalline serine hydroxymethyltransferase from the microbial source was obtained in the apo form and found to be homogeneous. Amino acid analysis revealed that the enzyme had higher value per subunit for acidic and neutral amino acids than that from rabbit liver. The carboxy-terminal amino acid analysis suggested the sequence Ile-Ala-Tyr. PMID- 3094514 TI - Identification of poly G bound to thymidylate synthase. AB - Thymidylate synthase activity is increased in some methotrexate-resistant strains of Streptococcus faecium. The purified enzyme is associated with a polynucleotide which is not removed by dialysis. This polynucleotide contains one mole each of purine ribose and phosphate per mole base. Phosphate analyses after incubation with digestive enzymes indicate a tetranucleotide with one terminal phosphate. The constituent nucleosides are recovered quantitatively in a specific assay for guanosine. On HPLC, they are inseparable from authentic guanosine and the UV spectrum after HPLC is identical to that of guanosine. We conclude that poly G (GpGpGpGp) is bound to thymidylate synthase. PMID- 3094515 TI - Purification and characterization of a form of cytochrome P-450 with high specificity for aflatoxin B1 from 3-methylcholanthrene-treated hamster liver. AB - A form of cytochrome P-450 highly active in inducing mutagenicity of aflatoxin B1 was purified to a specific content of 15.1 nmol/mg of protein from 3 methylcholanthrene-treated hamster liver. This species of cytochrome P-450, having its absorption maximum at 448.5 nm in carbon monoxide-complex of reduced form and low spin ferric ion, is of molecular weight of 56,000 and distinctly different in physicochemical and catalytic properties from major forms of cytochrome P-450 purified from phenobarbital- or 3-methylcholanthrene-treated rat liver. In the induction of aflatoxin B1 mutagenicity, this hamster cytochrome P 450 is 50 times more potent than those from rat liver. PMID- 3094516 TI - A p60v-src-related tyrosine kinase in the acetylcholine receptor-rich membranes of Narke japonica: association and dissociation of phosphatidylinositol kinase activity. AB - We have isolated a tyrosine-specific protein kinase from the acetylcholine receptor (AChR)-rich membranes of the electric ray Narke japonica. The enzyme is immunologically related to p60v-src, the product of the transforming gene of Rous sarcoma virus. A substantial phosphatidylinositol (PI) kinase activity was associated with this enzyme when it was purified through tyrosine-agarose affinity chromatography used previously for the purification of p60v-src. However, by subsequent chromatography on casein-agarose, most of the associated PI kinase activity was separated from the tyrosine kinase activity. The results suggest that the tyrosine-specific protein kinase in the AChR-rich membranes of N. japonica has no intrinsic PI kinase activity. PMID- 3094517 TI - Direct 1H n.m.r. determination of the stereochemical course of hydrolyses catalysed by glucanase components of the cellulase complex. AB - The stereochemical courses of the hydrolyses catalysed by three glycosidases have been determined directly by 1H nmr. The anomeric configuration of the initially formed product was ascertained in each case by observation of the chemical shift and coupling constant of the anomeric proton at the new hemiacetal centre. Two of the enzymes investigated, an endo-glucanase and an exo-glucanase are components of the cellulase complex of Cellulomonas fimi. The third enzyme is the beta glucosidase from almond emulsin. Two of these enzymes, the exo-glucanase and the almond beta-glucosidase catalysed hydrolysis with retention of anomeric configuration, in agreement with previous observations on the almond enzyme. The endo-glucanase catalysed hydrolysis with inversion of configuration, this result being confirmed by optical rotation measurements. This 1H nmr approach has several advantages over other techniques in that it is applicable to a wide variety of glycosidases and substrates and it is non-destructive, allowing recovery of the enzyme. PMID- 3094518 TI - Inhibition by antioxidants of agonist evoked cytosolic Ca++ increase, ATP secretion and aggregation of aspirinated human platelets. AB - The synthetic antioxidants butylated hydroxytoluene (BHT), nordihydroguaiaretic acid and the one-electron donor 1,1'-dimethylferrocene, inhibit cytosolic Ca++ increase, shape change, aggregation and ATP secretion in aspirinated washed human platelets stimulated by thrombin, vasopressin and platelet-activating factor. The antioxidants also inhibit cytosolic Ca++ increase originating from intracellular stores in the presence of EGTA. The effect of phorbol ester (TPA), which promotes platelet aggregation and secretion without raising the cytosolic Ca++, is also antioxidant-sensitive. Since agonist activation of aspirinated platelets does not involve cyclooxygenase or lipoxygenase metabolites, it is suggested that other yet unknown free radical-dependent pathways are involved in the mechanism of platelet activation, both in the protein kinase C-independent events leading to the cytosolic Ca++ increase, and in those, largely protein kinase C-dependent, leading to aggregation and ATP secretion. PMID- 3094519 TI - A possible role of protein kinase C in regulating prostaglandin synthesis of mouse peritoneal macrophages. AB - The addition of the analogue of diacylglycerol, 1-oleoyl-2-acetylglycerol (OAG), to resident macrophages isolated from the peritoneal cavity of mice led to a dose and time dependent increase in the synthesis of prostaglandin E. This was likely due to an enhanced amount of arachidonic acid available for eicosanoid synthesis as OAG suppressed the incorporation of arachidonic acid into cellular phospholipids by inhibiting acyl-CoA:lysophosphatide acyltransferase. Since OAG has been shown to activate protein kinase C in various cells, these data lead us to suggest that synthesis of eicosanoids in peritoneal macrophages is mediated by the activation of protein kinase C. PMID- 3094520 TI - Formation of 8-hydroxyguanine residues in cellular DNA exposed to the carcinogen 4-nitroquinoline 1-oxide. AB - 8-Hydroxyguanine (8-OH-Gua) residues were formed in DNA of Ehrlich ascites cells exposed to the carcinogen 4-nitroquinoline 1-oxide. Formation of 8-OH-Gua was confirmed by chemical treatment of calf thymus DNA with the proximate metabolite of this carcinogen, 4-hydroxyaminoquinoline 1-oxide, together with seryl adenosine monophosphate. The ratio of the rates of formations of 8-OH-Gua and the quinoline-bound adducts was about 0.2-0.3. A conceivable mechanism of formation of 8-OH-Gua is proposed. PMID- 3094521 TI - Amphiphilic growth hormone releasing factor (GRF) analogs: peptide design and biological activity in vivo. AB - The first twenty-nine amino acids of human Growth Hormone Releasing Factor (hGRF) possess a distinct amphiphilic character. This is seen as twisted hydrophobic and hydrophilic bands in the helical net projection. Four amidated analogs were designed by optimizing amphiphilic and helical potentials of the native sequence. These designed analogs, with up to eight-amino acid changes, were tested in sheep via intravenous injection. The growth hormone-stimulating activities of the analogs were significantly higher when compared to bovine Growth Hormone Releasing Factor (bGRF44-NH2). This suggests that the amphiphilic conformation of GRF(1-29) is important to the receptor. PMID- 3094522 TI - Acetylcholine receptor dimers are stabilized by extracellular disulfide bonding. AB - Torpedo acetylcholine receptor (AcChR) exists predominantly as dimers, formed by two monomers held together by a disulfide bridge(s). The dimers are easily cleaved to monomers by reducing agents. 2-mercaptoethanesulfonic acid is shown to be a membrane-impermeant reducing agent which cleaves receptor dimers when it is present only on the outside of intact membrane vesicles. There is no increase in the extent of cleavage when 2-mercaptoethanesulfonic acid is also loaded inside the vesicles. Therefore the disulfide bond(s) involved in the dimerization of the Torpedo acetylcholine receptor is (are) formed by cysteine residues which are exposed on the extracellular side of the membrane. PMID- 3094523 TI - Phosphorylation of liver pyruvate kinase by Ca++/calmodulin-dependent protein kinase: characterization of two phosphorylation sites. AB - Rat liver pyruvate kinase is phosphorylated by calcium/calmodulin-dependent protein kinase II at serine and threonine residues in a 3-4 kDa CNBr fragment located near the amino terminus. The two sites of phosphorylation were separated by reverse-phase HPLC of a thermolysin digest. Sequence analysis established the sites of phosphorylation as follows: Leu-Arg-Arg-Ala-Ser(PO4)-Val-Ala-Gln-Leu Thr(PO4)-Gln-Glu. PMID- 3094524 TI - Arachidonic acid releasing systems in pig aorta endothelial cells. AB - Endothelial cells synthesize prostacyclin both from platelet-derived endoperoxides and from the arachidonic acid released from its intracellular stores. The mechanisms controlling this release does not appear to be mediated through phospholipid methylation but by means of phosphoinositide hydrolysis. As yet two possible mechanisms have so far been proposed to regulate arachidonic acid release in a number of cellular systems: phospholipase C-controlled phospholipase A2 activity or phospholipase C-diglyceride lipase system. The results presented here show that using phospholipases inhibitors is not a reliable strategy to study arachidonic acid release in cultures of endothelial cells. Our data also strongly suggest that the release of prostacyclin may be accounted in these cells for by a phospholipase C-diglyceride lipase system. PMID- 3094525 TI - Biosynthesis of riboflavin. Enzymatic formation of 6,7-dimethyl-8-ribityllumazine by heavy riboflavin synthase from Bacillus subtilis. AB - The beta subunits of heavy riboflavin synthase catalyze the formation of 6,7 dimethyl-8-ribityllumazine from 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione and a carbohydrate phosphate, Compound X. 5-Amino-6-ribitylamino-2,4(1H,3H) pyrimidinedione 5'-phosphate is not a substrate for the enzyme, although it is an established intermediate in the biosynthesis of riboflavin. It follows that this pyrimidine phosphate must be dephosphorylated prior to the formation of 6,7 dimethyl-8-ribityllumazine. PMID- 3094526 TI - On the nature of cellular ADP-ribosyltransferase from rat liver specific for elongation factor 2. AB - A cellular ADP-ribosyltransferase, specific for elongation factor 2 (EF-2), is found in extracts from rat liver. Co-migrating with EF-2 throughout purification, this activity is, moreover, located in the protein bands corresponding to EF-2 after native or sodium dodecyl sulfate polyacrylamide gel electrophoresis. The observed activity is thus implicated to be an inherent property of EF-2. Preincubation of EF-2 with GuoPPCH2Pox inhibits endogenous, but not diphtheria toxin catalyzed ADP-ribosylation. PMID- 3094527 TI - Component C of the methylcoenzyme M methylreductase system contains bound 7 mercaptoheptanoylthreonine phosphate (HS-HTP). AB - The structure of component B of the methylcoenzyme M methylreductase system of Methanobacterium thermoautotrophicum was recently found to be 7 mercaptoheptanoylthreonine phosphate (HS-HTP). The work described here demonstrates that this compound is found in two forms: enzyme-free and enzyme bound. HS-HTP was found to be bound to component C of the methylcoenzyme M methylreductase system. The cofactor extracted from the protein by heat denaturation was found to comigrate with the mixed disulfide of HS-HTP and 2 mercaptoethanol by high-performance liquid chromatography, suggesting HS-HTP is not modified in the bound state. PMID- 3094529 TI - Proline inhibits N2-fixation in Anabaena 7120. AB - The uptake and metabolism of proline by Anabaena 7120 is demonstrated. Uptake is linear over the first hour and it appears that the rate of proline oxidation is sufficient to account for growth is suggested by the finding that exogenous proline represses heterocyst differentiation and inhibits nitrogen fixation in Anabaena 7120, without affecting growth rate. PMID- 3094528 TI - Identification and characterization of the tyrosine protein kinases of rat spleen. AB - High levels of tyrosine protein kinase have been recently detected in the membranes of rat spleen. In the present report the tyrosine protein kinase activity of the 30,000 x g pellet of rat spleen has been solubilized and partially purified by ion exchange and gel permeation chromatography. Two peaks of tyrosine protein kinase of Mr 35,000 (TPK-I) and Mr 40,000 (TPK-II) have been resolved. These kinases were free of the EGF receptor and insulin receptor tyrosine protein kinases. Although TPK-I and TPK-II phosphorylated angiotensin II, casein, histone, tubulin, phosphorylase b, and p36 they differed from each other in preference for the substrates. Both tyrosine protein kinases did not phosphorylate anti-pp60v-src IgG. PMID- 3094530 TI - Preparation and spectroscopic studies of cobalt(II)-substituted cucumber basic blue protein "plantacyanin". AB - The cobalt(II) derivative of cucumber basic blue copper protein "plantacyanin" has been prepared. The visible absorption, circular dichroic and magnetic circular dichroic spectra of Co(II)-plantacyanin are similar to those of Co(II) plastocyanin, indicating that the stereochemistry of Co(II) is tetrahedral and at least one cysteinyl ligand around Co(II) ion is responsible for the strong charge transfer bands at 331 and ca. 390 nm. PMID- 3094531 TI - A retinal heat shock protein is associated with elements of the cytoskeleton and binds to calmodulin. AB - Elevation of body temperature to a level similar to that attained during fever induces a disaggregation of polysomes in the mammalian retina and induction of a 74K heat shock protein (hsp74). Induced retinal hsp74 copurifies with twice cycled microtubules and also with purified intermediate filaments, is precipitated by antibodies prepared against purified Tau proteins and binds to calmodulin. PMID- 3094532 TI - A spectrophotometric study of vitamin B2 and its coenzyme forms binding to muscle glycogen phosphorylase b. AB - The vitamin B2 and its coenzyme forms binding to glycogen phosphorylase b from rabbit skeletal muscle has been studied by the spectrophotometric method. The spectral properties of riboflavin, FMN and FAD bound to muscle glycogen phosphorylase b were found to be identical at the wavelengths of 300 to 500 nm. According to data on spectrophotometric titration of muscle glycogen phosphorylase b by FMN, each subunit of the enzyme contains one flavin-binding site. PMID- 3094533 TI - The metabolic significance of pentose cycle measurements in perfused liver. AB - The controversial dissension concerning the nature of the pentose cycle in liver is investigated. The metabolism of [2-14C]Glc and [1-14C]Rib in chronically perfused normal and regenerating rabbit liver and acutely perfused rat liver are used to test the mechanistic predictions and contribution of the F-type pentose cycle. 14C was traced in Glc, Glc 6-P, Fru 6-P, glycogen and Rib 5-P. None of the data complied with the critical theoretical limits set for the C-1/C-3 ratio (the identity badge of the F-type pentose cycle or pathway) for all values of F-type PC from 0-100%. Thus apparent F-type PC measurements using the Katz & Wood method gave a wide scatter of calculated values. The 14C distributions in Rib 5-P do not conform with the predictions of the F-type PC but are in agreement with the many previous results of similar experiments reported by Hiatt and co-workers. In perfused rat liver the C-1/C-3 constants in Glc 6-P and glycogen also failed to conform with F-PC theory following the metabolism of [2-14C]Glc. The metabolism of [5-14C]Glc and distribution of 14C in Glc 6-P and glycogen showed that L-type PC was 18%, in close agreement with a previous published value of 22% for rat hepatocytes. Metabolism of [6-14C]Glc and [4-14C]Glc (as [4,5,6-14C]Glc) showed that Pyruvate Recycling was active in perfused rat liver. None of the data from these comprehensive investigations can confirm the results of the recent study reported by the Landau laboratory on the pentose pathway metabolism of Glc and Rib in perfused rat liver. PMID- 3094534 TI - Selective inhibition of mitochondrial NADH-ubiquinone reductase (Complex I) by an alkyl polyoxyethylene ether. AB - The detergent mono-n-dodecyl octaoxyethylene ether tightly bound to mitochondrial electron-transport particles and below its critical micellar concentration inhibited the NADH oxidase activity, but not the succinate oxidase activity. The result indicates that the inhibition site is in the Complex I segment. The detergent inhibited rotenone-sensitive NADH-ubiquinone reductase activity, but not NADH-ferricyanide reductase activity, of isolated Complex I. Partial removal of phospholipids from Complex I from 18.8% (w/w) to 14.5% significantly decreased its susceptibility to the inhibitor as well as to rotenone. These results show that the binding site of the detergent responsible for the inhibition lies between the NADH dehydrogenase of flavoprotein and ubiquinone in Complex I and that the binding of the detergent to the site requires phospholipids. PMID- 3094535 TI - In vivo metabolism and reaction with DNA of the cytostatic agent, 5-(3,3-dimethyl 1-triazeno)imidazole-4-carboxamide (DTIC). AB - The cytostatic drug dacarbazine [DTIC, 5-(3,3-dimethyl-1-triazeno)imidazole-4 carboxamide] is strongly carcinogenic in rats. Bioactivation of DTIC yields a methylating intermediate but the extent of interaction with cellular macromolecules has not previously been reported. Following a single i.p. injection of [14C-methyl]DTIC, exhalation of 14CO2 occurred with a t1/2 max of approximately 2 hr (0.95 mg/kg) and 2.5 hr (95 mg/kg). Of the total radioactivity administered, 8.5% was exhaled as 14CO2; 54% was excreted via the urine, predominantly as unchanged DTIC. In liver, kidney and lung, formation of 7 [14C]methylguanine in DNA and RNA was directly proportional with dose. DNA methylation by a single dose of DTIC (9.8 mg/kg; 5 hr survival time) was highest in liver (35 mumoles 7-methylguanine/mole guanine), followed by kidney (25 mumoles) and lung (20 mumoles). The remainder tissues showed 7-methylguanine concentrations approximately 50% of those in liver DNA, with the exception of the brain which had a very low extent of DNA modification (approximately 1 mumole/mole guanine). At the specific radioactivity used (48 mCi/mmole), the promutagenic base O6-methylguanine was only detectable in liver, kidney, lung, and stomach DNA (0.6-0.8 mumoles/mole guanine). Autoradiographic studies revealed a diffuse distribution of reaction products in rat liver. In contrast, N nitrosodimethylamine and related carcinogens known to be bioactivated by the hepatic cytochrome P-450 system show a predominantly centrilobular distribution. This difference may be due to the greater stability of proximate carcinogens generated by alpha-C hydroxylation at one of the methyl groups of DTIC. PMID- 3094536 TI - The oxidation of tryptamine by the two forms of monoamine oxidase in human tissues. AB - The selective monoamine oxidase inhibitors clorgyline and (-)-deprenyl have been used to determine the activities of monoamine oxidase-A and -B towards tryptamine in several human tissues. The results were compared with those obtained with the A-form-selective substrate 5-hydroxytryptamine, the B-form-selective substrate 2 phenethylamine and the common substrate tyramine. Tryptamine was found to be a substrate for both forms of the enzyme in human liver, kidney cortex and medulla and in seven different brain regions. The Km values of the two forms towards this substrate were similar in all the human tissues examined but the maximum velocities differed. Thus the A-form would contribute approximately 50% of the total monoamine oxidase activity towards this substrate in human cerebral cortex, whereas it would contribute about 60% in kidney cortex and medulla and 75% in liver. These results suggest that both forms of monoamine oxidase would contribute to the metabolism of tryptamine in human tissues and are difficult to reconcile with suggestions that tryptamine excretion may provide a simple index of monoamine oxidase-A inhibition. PMID- 3094537 TI - Activation of phospholipase A2 by carbon tetrachloride in isolated rat hepatocytes. AB - Freshly isolated rat hepatocytes were exposed to carbon tetrachloride (CCl4) for periods up to 4 hr. Phospholipase A2 activity of these preparations was determined by measuring either the release of [3H]arachidonic acid from cellular phospholipids prelabeled with [3H]arachidonic acid or by measuring the formation of [14C]lysophosphatidylethanolamine from cellular lipids prelabeled with [14C]ethanolamine. Through the use of hexane-partition extraction and thin-layer chromatographic analysis of hepatocyte lipid extracts it was found that CCl4 stimulated phospholipase A2 activity in a dose- and time-dependent manner. Carbon tetrachloride at concentrations of 0.23 to 1.3 mM produced a 1.4- to 5.3-fold increase in phospholipase activity which was initiated within 30-60 min of incubation at 37 degrees. The role of phospholipase activation as a secondary mechanism of CCl4-induced hepatocyte injury is discussed. PMID- 3094538 TI - Liver carbonic anhydrase and urea synthesis. The effect of diuretics. AB - In isolated perfused rat liver, urea synthesis is rapid and reversibly inhibited not only by the well-known carbonic anhydrase inhibitors acetazolamide, methazolamide and ethoxzolamide, but also by diuretics, like xipamide, mefruside, chlortalidone, and chlorothiazide. Furosemide was without effect. Similar to findings with isolated perfused rat liver, acetazolamide inhibits urea synthesis from ammonium ions in normal and cirrhotic human liver slices. Inhibition of urea synthesis by xipamide and acetazolamide is accompanied by a 70% decrease of the cellular citrulline content and the tissue levels of 2-oxoglutarate and citrate, suggesting a block of urea synthesis at a step prior to citrulline formation. At a constant extracellular pH (7.4), inhibition of urea synthesis by xipamide, mefruside and acetazolamide was overcome by increasing the extracellular concentrations of HCO3- and CO2 to above twice the normal values. This shows that inhibition of urea synthesis by these diuretics is not due to an unspecific inhibition of one of the urea cycle enzymes but is due to an inhibition of mitochondrial carbonic anhydrase and therefore due to an impaired HCO3- provision for mitochondrial carbamoylphosphate synthesis. It is concluded that the activity of mitochondrial carbonic anhydrase is required for urea synthesis also in human liver and that several diuretics impair urea synthesis by inhibition of mitochondrial carbonic anhydrase. The pathophysiological significance of these data is discussed with respect to the development of diuretics-induced hyperammonemia and alkalosis in liver disease. PMID- 3094539 TI - 2,5,2',5'-Tetrachlorobiphenyl impairs the bioenergetic functions of isolated rat liver mitochondria. AB - The effects of 2,5,2',5'-tetrachlorobiphenyl (25TCB) on parameters related to the bioenergetic functions of isolated rat liver mitochondria were investigated. State 3 respiration was inhibited by 25TCB with both succinate and glutamate/malate as the respiratory substrates. The extent of inhibition with succinate was larger than that observed with glutamate/malate. The concentration of 25TCB required to cause 50% inhibition for succinate was 51 microM, but with glutamate/malate, only 53% inhibition was observed at 200 microM. 25TCB stimulated state 4 respiration after 1-2 min lag period; state 4 respiration in the presence of glutamate/malate was more intensely stimulated by 25TCB than in the presence of succinate. 25TCB dissipated the membrane potential across the mitochondrial membranes. Isolated rat liver mitochondria accumulate large amounts of Ca2+ at the expense of respiration-linked energy (substrate oxidation) or of that provided by the hydrolysis of ATP by the mitochondrial ATPase. The Ca2+ accumulation by mitochondria was severely depressed by 25TCB when the energy was supplied by respiration. Furthermore, the inhibition of Ca2+ accumulation by 25TCB with succinate was greater than that produced with glutamate/malate. On the other hand, with ATP as the source of energy, 25TCB inhibited Ca2+ accumulation at high concentrations. 25TCB also released Ca2+ from mitochondria that had already accumulated Ca2+, indicating that mitochondrial membrane integrity was damaged by the intercalation of 25TCB. These results show that 25TCB impairs mitochondrial energy production, and inhibits Ca2+ sequestration by mitochondria. PMID- 3094541 TI - Augmentation of leukotriene C4 and D4 release due to severe stenosis in the canine coronary artery stimulated by the calcium ionophore A23187. AB - In dogs undergoing 24- or 72-hr severe narrowing of the left anterior descending coronary artery (LAD), the in vitro formation of immunoreactive leukotriene C4 (LTC4) by the stenosed LAD was greatly augmented by 1 microM A23187 in a 10-min incubation at 37 degrees. This stimulated LTC4 formation was abolished by 30 microM nordihydroguaiaretic acid (NDGA). The incubation products were identified by high performance liquid chromatography and radioimmunoassay to be largely composed of LTC4 and LTD4 in similar proportion. In contrast to the stenosed LAD, the non-stenotic left circumflex coronary artery, apex of the heart, and renal artery of the same experimental animals failed to respond to the calcium ionophore up to 10 microM. The vascular and cardiac tissues from sham-operated animals also remained quiescent in the presence of A23187. The normal coronary artery showed low levels of leukotriene formation and was resistant to the ionophore. It is proposed that a latent portion of leukotriene synthesis, which can be triggered by the calcium ionophore, may play a significant role in the pathogenesis of coronary artery spasm associated with acute myocardial infarction and angina pectoris in patients with obstructive coronary artery disease. PMID- 3094540 TI - Lack of specificity of melittin as a probe for insulin release mediated by endogenous phospholipase A2 or lipoxygenase. AB - The effects of the basic polypeptide melittin on islet phospholipid degradation and insulin release were studied in static incubations of intact rat islets as a possible model of endogenous phospholipase A2 (PLA2) activation. Melittin (2 micrograms/ml) increased [3H]-arachidonic acid [( 3H]-AA) release from prelabeled islets (at 1.7 mM glucose) to 371% of basal values. Concomitantly, melittin induced degradation of islet phospholipids labeled with [3H]-AA or [14C]-stearic acid, and led to the accumulation of stearate-labeled (but not AA-labeled) lysophosphatidylcholine (LPC, 605% of control). These findings suggested, for the first time in intact rat islets, the presence and activation of a PLA2. Under identical conditions, melittin initiated insulin secretion (at 1.7 mM glucose) in a manner that represented stimulation of physiologic exocytosis--that is, it was dose-dependent, reversible (albeit slowly), unassociated with impairment of other physiologic islet processes (i.e. the response to 16.7 mM glucose after removal of the drug) and inhibitable by reduced ambient temperature. The effect of melittin seemed to be independent of extracellular Ca2+ influx or mobilization of intracellular Ca2+ stores but was blocked by nickel or lanthanum, indirectly suggesting that the effects of this cationic amphiphile might involve a superficial pool of Ca2+. Unexpectedly, melittin-induced insulin release (at least at low glucose concentrations) was not greatly or consistently altered by a battery of inhibitors of endogenous PLA2 or of enzymes affecting AA oxygenation. Furthermore, significant contamination by bee venom PLA2 of the commercially available melittin preparation was found, and insulin release could be induced by pure bee venom PLA2, probably through the generation of lysophospholipids. Although estimates of the amount of PLA2 in the melittin preparation suggested that such contamination was insufficient to explain at least some of the islet phospholipid hydrolysis and insulin release caused by melittin, we conclude that this agent does not serve as a specific probe of the role of endogenous PLA2 or of AA lipoxygenation in hormone release. PMID- 3094542 TI - Induction of acute renal porphyria in Japanese quail by Aroclor 1254. PMID- 3094543 TI - Prostaglandin synthase dependent aldrin epoxidation in hepatic and extrahepatic tissues of rats. PMID- 3094544 TI - Metabolism of benzoic acid by stimulated polymorphonuclear cells. PMID- 3094545 TI - Discordant effects of prednisone on anticardiolipin antibodies and the lupus anticoagulant. PMID- 3094546 TI - Effect of cilostazol on experimental cerebral infarction in rabbits. AB - The effects of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3, 4-dihydro-2(1H) quinolinone (cilostazol, OPC-13013), acetylsalicylic acid (ASA) and ifenprodil on experimentally induced cerebral infarction were studied in anesthetized rabbits. Cerebral infarction was induced by injecting arachidonic acid (AA) at a dose of 0.5 mg/kg into the unilateral intracarotid artery. After the injection of AA, the brain was perfused with Indian ink, and the degree of thrombus formation was determined by calculating the percentage of perfused area in the hemispheres. The intracarotid injection of AA produced a non-perfused area amounting to 84% of the hemisphere in the injected side and 41% of the hemisphere in the non-injected side. Intravenously administered cilostazol did not produce a definite reduction in carbon-deficient area at 0.1 mg/kg, but it did produce a 49% reduction in the injected side and a 55% reduction in the entire brain at 1 mg/kg. ASA produced a 60% reduction in the carbon-deficient area in the injected side and a 62% reduction in the entire brain at 1 mg/kg. Ifenprodil at 1 mg/kg produced only a 19% reduction in the carbon-deficient area in the injected side. PMID- 3094547 TI - Right-heart echocontrast in the anesthetized dog after i.v. administration of a new standardized sonographic contrast agent. 3rd communication: comparison of various contrast agents employed in contrast echocardiography. AB - Right-ventricular contrast provided by the new standardized sonographic contrast agent SH U 454, which consists of pure galactose microparticles, with 300 mg microparticles/ml and by 5 other currently employed ultrasonic contrast media was examined by 2 D echocardiography in 10 anesthetized female beagle dogs (6.8-12.7 kg) following i.v. administration. With a 5-min interval between injections each animal was given 3 injections of 2 ml of each formulation in random order using an injection speed of approximately 2 ml/s. The echocardiographic investigation was recorded on videotape and the contrast assessed blind using a visual score system (rating 0-5) by two investigators working independently and also by a videodensitometer. Only SH U 454 caused an intense, homogeneous and reproducible opacification of the right heart chambers. By comparison with other formulations for right-heart echocontrast, SH U 454 was significantly superior (p less than 0.05) in every parameter assessed. PMID- 3094548 TI - [Bioavailability of a valproic acid preparation. The relative bioavailability of enteric-resistant valproic acid preparations in tablet form with simultaneously administered tetradeuterated valproic acid as the bioavailability reference]. AB - The relative bioavailability was measured for the 150-, 300-, and 600-mg enteric coated Leptilan tablets (valproic acid, sodium salt) using a new method. Simultaneously an equimolar amount of a tetradeuterated valproic acid - di-(2,3 dideutero-n-propyl)-acetic acid - was given as an aqueous solution of the sodium salt. This methodology excludes effects on the two partial pharmacokinetics caused by time-dependent intraindividual variations of the metabolising capacity or other biochemical or physiological changes in the body of the volunteer. Therefore, this methodology gives already reliable data for bioavailability when using only small numbers of volunteers. The relative bioavailability of the enteric coated Leptilan tablets was 95.5 +/- 0.6%, 104.4 +/- 7.6%, and 100.7 +/- 2.4% (mean from experiments with 3 volunteers each) for the 150-, 300-, and 600 mg tablets respectively. PMID- 3094549 TI - The practice of audiology. A national perspective. PMID- 3094551 TI - Plasma low density lipoprotein accumulation in aortas of hypercholesterolemic swine correlates with modifications in aortic glycosaminoglycan composition. AB - Arterial wall sulfated glycosaminoglycans (GAG) of matrix proteoglycans have been implicated in the retention of plasma low density lipoproteins in the early stages of atherosclerosis. We have studied modifications in porcine aortic GAG composition after 4 and 11 weeks of diet-induced hypercholesterolemia. After these time intervals no grossly visible atherosclerotic lesions were discerned. GAG changes were correlated with tissue LDL accumulation estimated by quantification of immunochemically-identifiable apolipoprotein B (apoB). Values of apoB ranged from less than 10 to 250 ng/mg wet weight of aorta, and correlated significantly with tissue total cholesterol contents. Although total GAG concentrations did not differ between a normolipemic control and the two diet groups, apoB showed a significantly positive correlation with the percent of total GAG that was chondroitin sulfate and a significantly negative correlation with the percent of total GAG that was dermatan sulfate. Total tissue cholesterol likewise demonstrated similar correlations with GAG. Since areas of the aorta were chosen that were devoid of intimal thickening, these metabolic changes may occur in the inner part of the arterial tunica media. The results suggest that the accumulation of plasma LDL in the arterial wall following hypercholesterolemia may induce alterations in arterial GAG composition, presumably by affecting GAG synthesis by medial smooth muscle cells. PMID- 3094550 TI - Apolipoprotein B release from activated human platelets. AB - Apolipoprotein B (apoB) release from activated washed human platelets was measured by enzyme-linked immunosorbent assay (ELISA) using monospecific rabbit antibodies to human low density lipoprotein (LDL). Activation of platelets with thrombin, Ca2+-ionophore A23187 or stable analogue of prostaglandin endoperoxides U46619 stimulated release of approximately 20 ng apoB/10(8) platelets. Thrombin induced apoB release was inhibited by the prostacyclin analogue carbacyclin. Dose response curves of thrombin stimulation and carbacyclin inhibition of apoB and beta-thromboglobulin (beta-TG) release were very similar. Treatment of platelets with heparin did not remove significant amounts of apoB or affect the subsequent release of apoB induced by thrombin. The results of density gradient ultracentrifugation indicated that most of the apoB was released in the LDL density range. These data suggest that human platelets contain immunoreactive apoB, which can be released during platelet activation. PMID- 3094552 TI - The analysis of hazards and the hazards of analysis: reflections on air traffic safety management. AB - The justification of investments in air traffic control systems has typically been based on risk-benefit analyses of the safety of air traffic. But the lack of empirical evidence concerning collisions between aircraft, and the problems of very small numbers make risk analysis inadequate. The pitfalls of risk analysis are discussed in this paper. A framework for safety analysis is proposed where safety is to be assured rather than traded off in the economic sense against other expenditures on the system. The trade-off in the analysis of large investments on control technologies should be between economy and efficiency and should no include safety. PMID- 3094553 TI - Isoproterenol inhibition of horse serum cholinesterase is connected with subunit dissociation. AB - Tetrameric cholinesterase from horse serum undergoes concentration-dependent dissociation. The dimer is highly stable so that even on SDS polyacrylamide gels subunit dissociation to the 80-kDa polypeptide chains is incomplete. Glutaraldehyde cross-linking confirms this finding, giving rise to a tetramer: dimer ratio of approximately 1:1. The beta-adrenergic agent isoproterenol acts as an inhibitor of the enzyme with respect to butyrylthiocholine hydrolysis; inhibition kinetics point to a dissociative effect of the ligand as the underlying mechanism (Soylemez, Z. & Ozer, I. (1985) Comp. Biochem. Physiol. 81c, 433-437). Evidence from sedimentation analysis confirms this hypothetical mechanism: the sedimentation coefficient in the presence of saturating concentrations of both the substrate butyrylthiocholine and the inhibitor isoproterenol shows a 35 +/- 5% decrease; in high speed sedimentation equilibria the weight average molecular mass is shifted from the tetramer (Mr = 312 +/- 12 kDa) to the dimer (Mr = 160 +/- 10 kDa). The transition is complete at isoproterenol concentrations below saturation. Applying glutaraldehyde cross linking to monitor the particle distribution at varying isoproterenol concentrations confirms the change in quaternary structure in a qualitative way. Enzyme concentrations applied in the present experiments are in the range of the concentration of cholinesterase in horse serum. Therefore the dissociative mechanism of isoproterenol on the enzyme may be of biological significance. PMID- 3094554 TI - Urea synthesis and CO2/HCO3- compartmentation in isolated perfused rat liver. AB - With physiological portal HCO3- and CO2 concentrations of 25mM and 1.2mM in the perfusate, respectively, acetazolamide inhibited urea synthesis from NH4Cl in isolated perfused rat liver by 50-60%, whereas urea synthesis from glutamine was inhibited by only 10-15%. A decreased sensitivity of urea synthesis from glutamine to acetazolamide inhibition was also observed when the extracellular HCO3- and CO2 concentrations were varied from 0-50mM and 0-2.4mM, respectively. Stimulation of intramitochondrial CO2 formation at pyruvate dehydrogenase with high pyruvate concentrations (7mM) was without effect on the acetazolamide sensitivity of urea synthesis from NH4Cl. Urea synthesis was studied under conditions of a limiting HCO3- supply for carbamoyl-phosphate synthesis. In the absence of externally added HCO3- or CO2, when 14CO2 was provided intracellularly by [U-14C]glutamine or [1-14C]-glutamine oxidation, acetazolamide had almost no effect on label incorporation into urea, whereas label incorporation from an added tracer H14CO3- dose was inhibited by about 70%. 14CO2 production from [U 14C]glutamine was about twice as high as from [1-14C]glutamine, indicating that about 50% of the CO2 produced from glutamine is formed at 2-oxoglutarate dehydrogenase. The fractional incorporation of 14CO2 into urea was about 13% with [1-14C]-as well as with [U-14C]glutamine. Addition of small concentrations of HCO3- (1.2mM) to the perfusate increased urea synthesis from glutamine by about 70%. This stimulation of urea synthesis was fully abolished by acetazolamide. The carbonate-dehydratase inhibitor prevented the incorporation of added HCO3- into urea, whereas incorporation of CO2 derived from glutamine degradation was unaffected. Without HCO3- and CO2 in the perfusion medium, when 14CO2 was provided by [1-14C]-pyruvate oxidation, acetazolamide inhibited urea synthesis from NH4Cl as well as 14C incorporation into urea by about 50%. Therefore carbonate-dehydratase activity is required for the utilization of extracellular CO2 or pyruvate-dehydrogenase-derived CO2 for urea synthesis, but not for CO2 derived from glutamine oxidation. This is further evidence for a special role of glutamine as substrate for urea synthesis. PMID- 3094555 TI - Further investigations of race:cultivar-specific induction of enzymes related to phytoalexin biosynthesis in soybean roots following infection with Phytophthora megasperma f.sp. glycinea. AB - The activities of the following enzymes in soybean roots were determined at early times after infection of the roots with zoospores of an incompatible or a compatible race of Phytophthora megasperma f.sp. glycinea: dimethylallyl diphosphate : 3,6a,9-trihydroxypterocarpan dimethylallyltransferase (prenyltransferase), an enzyme specific for glyceollin biosynthesis; NADPH cytochrome reductase and hydroxymethylglutaryl-CoA reductase, enzymes related to the glyceollin pathway; and isocitrate dehydrogenase. Already at 4 h after infection there was a higher activity of the prenyltransferase in the incompatible interaction than in the compatible interaction, and enzyme activity in the incompatible interaction increased considerably between 4 and 8 h after infection. In the compatible interaction prenyltransferase activity was only slightly higher than in uninfected roots. The activity of the other enzymes in infected roots was not significantly different from that in the uninfected roots. No qualitative differences could be detected between the two-dimensional patterns of unlabelled proteins or proteins labelled with L-[35S]methionine of infected and uninfected roots at early times after infection. We conclude from these and earlier results (A. Bonhoff et al. (1986) Arch. Biochem. Biophys. 246, 149-154) that infection of the soybean roots with an incompatible race of the fungus leads to selective induction of the phytoalexin pathway and presumably to induction of other as yet unknown defense mechanisms. PMID- 3094556 TI - Inhibition studies of glucose-6-phosphate dehydrogenase from tetracycline producing Streptomyces aureofaciens. AB - NAD-linked activity of glucose-6-phosphate dehydrogenase from both low-producing and high-producing strains of Streptomyces aureofaciens was inhibited by ATP, ADP, AMP and Pi. The inhibition constants indicate that ADP was the most potent inhibitor. The NADP-linked activity remained unaffected even at relatively high concentrations of these inhibitors. All inhibitions of the NAD-linked activity were competitive with respect to NAD and noncompetitive with respect to glucose-6 phosphate. The results represent a possible new regulatory mechanism of glucose-6 phosphate dehydrogenase from a streptomycete and emphasize its involvement in the regulation of the biosynthesis of tetracyclines. PMID- 3094557 TI - Inhibitory effects of Ge-132 (carboxyethyl germanium sesquioxide) derivatives on enkephalin-degrading enzymes. AB - Twenty-eight species of carboxyethyl germanium sesquioxide (Ge-132) derivatives were examined for their inhibitory effects on enkephalin-degrading enzymes that were purified from monkey brain, the longitudinal muscle layer of bovine small intestine, and human cerebrospinal fluid (CSF). A series of the sulfurized Ge-132 derivatives showed strong inhibition of these purified enzymes. The most effective ones were Ge-014 and Ge-107, which showed IC50 values of 60 and 100 micrograms/ml, respectively, for dipeptidylcarboxypeptidase from the longitudinal muscle layer. They also exhibited inhibitory activity against aminopeptidase from human CSF, the IC50 values being 450 and 440 micrograms/ml, respectively. Furthermore, these compounds showed inhibition of dipeptidylaminopeptidase from monkey brain and the longitudinal muscle layer of bovine small intestine. These compounds are expected to have analgesic effects due to their inhibition of the degradation of endogenous opioid peptides. PMID- 3094558 TI - Antibiotic therapy in children after tonsillectomy. PMID- 3094559 TI - Hydrophobic binding domains of rat intestinal maltase-glucoamylase. AB - Rat intestinal microvillus maltase-glucoamylase was isolated by detergent extraction and purification in the presence of protease inhibitors as previously described and incorporated into phospholipid vesicles. After purification of the vesicles on Sephadex G-50, maltase was labelled with 3-trifluoromethyl-3-(m [125I]iodophenyl) diazirine ([125I]TID) by photolysis using a water-jacketed mercury vapour lamp with a saturated CuSO4 filter. The labelled enzyme was extracted with acetone, resuspended in 1% Triton X-100, reincorporated into phospholipid vesicles, and digested with activated papain to release the hydrophilic polar head of the enzyme from the vesicle bilayer. Vesicle-bound and free enzyme components were separated on Sepharose 4B. Ninety percent of the enzymatic activity was free, while a similar percentage of radioactive label remained with the vesicles in keeping with the separation of an active polar headpiece from a labelled apolar peptide in the lipid bilayer. The vesicle fractions were subjected to chromatography on Sephadex LH-60 with ethanol--formic acid (7:3) as the eluant. A single radioactive peak (14 kilodaltons (kDa)) was separated from labelled lipid. Sodium dodecyl sulfate--polyacrylamide gel electrophoresis of the peak showed a radioactive doublet of 26-28 kDa, possibly representing a dimer. No other labelled peptides were found. These results suggest that detergent-solubilized maltase-glucoamylase is inserted into the phospholipid bilayer via an apolar peptide with a minimum molecular mass of 14 kDa. The peptide probably represents a terminal anchor segment of the 145-kDa subunit which is converted to 130 kDa when the membrane-bound enzyme is solubilized by papain. PMID- 3094560 TI - Effect of acidic phospholipids on apolipoprotein binding by artificial lipid particles in vivo. AB - Soybean triacylglycerol particles stabilized with soybean phosphatidylinositol (PI), bovine brain phosphatidylserine (PS), egg yolk phosphatidylcholine (PC) or mixtures of these acidic and neutral phospholipids were prepared with diameters ranging from 250 to 520 nm. Binding of apoproteins to the lipid particles was studied using the strategy of Connelly and Kuksis. The recoveries of the injected particles, which had undergone minimal changes in lipid composition, ranged rom 57% for the PC-stabilized emulsions to 21% for the emulsions stabilized with PS and 8% for the emulsions stabilized with PI. The apoprotein (apo) composition of the recovered particles showed characteristic qualitative and quantitative differences. The particles stabilized with PI and PS or PI phosphatidylethanolamine contained an unknown protein of molecular weight 117,000 (43-48%) and albumin (9-13%) as major components. The apoC-II, apoC-III, apoA-I, apoE, and apoA-IV were present as minor components in ratios that were the reverse of those seen for the PC-stabilized particles, which contained these proteins as major components. The relative strength of the binding of the proteins, which was determined by washing the particles with saline under standard conditions, also showed variations among the different particles and different apoproteins. The lipid particles stabilized with the acidic phospholipids had less total apoprotein and held it less tightly than the particles stabilized with PC. It is concluded that the binding of apoproteins by lipid particles stabilized with acidic phospholipids involves hydrophobic and ionic interactions, both of which may be physiologically important. PMID- 3094561 TI - Canthaxanthine (orobronze) retinopathy. AB - A 50-year-old white Australian male was found on routine examination to have small golden particles in the macular region of both eyes. A history of canthaxanthine (Orobronze) ingestion to produce skin bronzing was obtained. PMID- 3094562 TI - Evaluation of sodium cromoglycate and medrysone in the management of atopic keratoconjunctivitis: a double masked clinical study. AB - The efficacy of topical sodium cromoglycate and medrysone was evaluated in 38 patients suffering from atopic keratoconjunctivitis. It was found that medrysone (1%) significantly improved the symptoms of itching, watering, photophobia and hyperaemia, while sodium cromoglycate (2%) was found to be ineffective. Tear prostaglandin E2 and histamine levels did not decrease significantly after sodium cromoglycate therapy. The findings of the present study reveal that sodium cromoglycate has no significant role in the management of atopic keratoconjunctivitis. PMID- 3094563 TI - [Corticospinal neurons--a morphological review]. PMID- 3094564 TI - Effect of ethane-1-hydroxy-1,1-diphosphonate on ectopic bone formation induced by murine osteosarcoma-derived bone-inducing substance. AB - The effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP) on ectopic bone formation were studied qualitatively and quantitatively in an experimental system for ectopic bone formation induced by murine osteosarcoma-derived bone-inducing substance. At a low dose of EHDP (3 mg/kg per day i.p.), histologic sequelae of ectopic bone formation were normal, and the size of the induced bone mass was unaffected. At a high dose of EHDP (30 mg/kg per day i.p.), an unmineralized bone matrix with hematopoietic bone marrow was formed without evidence of retardation. This osteoid tissue showed no radiologic and histologic evidence of mineralization during the period of EHDP administration. When EHDP was withdrawn, its inhibitory effect on mineralization was reversed. The induced bone mass was almost the same size as that in controls. These results suggest that EHDP might not prevent ectopic bone matrix formation, but its mineralization and withdrawal of EHDP might lead to the formation of a normal bone similar in size to that formed without EHDP treatment. PMID- 3094565 TI - Cellular phosphate metabolism in patients receiving bisphosphonate therapy. AB - Patients with Paget's disease of bone were treated with oral disodium dihydrogen ethylidene-1-hydroxy-1,1-bisphosphonate (EHBP), a drug that is known to stimulate renal tubular reabsorption of orthophosphate (Pi). After 2 weeks of treatment, plasma Pi rose from 1.02 to 1.67 mmol/l. No increase in Pi was observed with the related drug, dichloromethylene bisphosphonate, which also reduces bone turnover in Paget's disease. Intravenous EHBP caused a more rapid increase in plasma Pi, but maximum hyperphosphatemia was not observed until 7-11 days after treatment commenced. It is therefore unlikely that this effect is due to an immediate action of EHBP on the luminal face of the renal brush border Pi transporter. After 2 weeks of oral EHBP, the increase in the Pi concentration in patients' erythrocytes was 31% compared with 64% in plasma. In blood platelets and leukocytes, negligible changes in cellular Pi occurred. The concentrations of 2,3 diphosphoglycerate, adenosine 5'-diphosphate (ADP) and adenosine 5'-triphosphate (ATP) were unaltered, indicating that these organic phosphates were not offsetting a potential change in cellular Pi. The decrease in erythrocyte/plasma distribution ratio for Pi was also observed in patients receiving intravenous EHBP. However, no change occurred in cell/plasma distribution of chloride, suggesting that this apparent regulation of cellular Pi did not arise from changes in erythrocyte membrane potential, pH, or water content. PMID- 3094566 TI - Congenital diverticulum of the heart arising from the coronary sinus. AB - A diverticulum originating from the coronary sinus was diagnosed by echocardiography in a two day old baby with hypoplastic left heart. At necropsy the diverticulum was seen to arise from the coronary sinus and it penetrated the right ventricular posterior wall. PMID- 3094568 TI - Hewlett-Packard HP47210A capnometer. PMID- 3094567 TI - An end-tidal sampler for use with slow response analysers during anaesthesia. AB - An end-tidal sampler is described which can be used during anaesthesia with spontaneous respiration at rates of at least 60 b.p.m. It can be used with slow response analysers such as refractometers and fuel cells to indicate end-tidal concentrations. It can also be used to extend the scope of those breath-to-breath analysers which have a response time which is too slow for the respiratory rates which may occur during anaesthesia with spontaneous breathing. Using the device, mean PCO2 of the samples was 0.13 kPa less than the corresponding values for the end-expiratory PCO2 measured by conventional breath-by-breath analysis. Full response was achieved in 12 breaths. PMID- 3094570 TI - Flecainide: single and multiple oral dose kinetics, absolute bioavailability and effect of food and antacid in man. AB - The kinetics of flecainide after single intravenous (2 mg kg-1) and oral (200 mg) dosing, absolute bioavailability, effects of food and aluminium hydroxide on flecainide absorption and steady-state kinetics following twice daily oral dosing (200 mg) have been evaluated in ten healthy subjects. Absolute bioavailability of oral flecainide averaged 70% (range 60-86%). Rate and extent of flecainide absorption were not significantly affected by food nor by concomitantly administered aluminium hydroxide. The apparent volume of distribution of 5.5 +/- 0.3 l kg-1 indicates wide distribution of flecainide in tissues. Estimated elimination half-lives from plasma data averaged 9.3 to 12.4 h (single oral dose studies), 11.8 h (single i.v. dose), and 11.5 h (multiple oral dose). Half-lives calculated from urinary excretion data corresponded well with those calculated from plasma data. Flecainide elimination takes place both by nonrenal (metabolic) clearance and renal excretion of the intact drug involving glomerular filtration and active tubular secretion. Following i.v. dosing CLNR and CLR averaged respectively 3.24 +/- 0.80 and 2.38 +/- 0.49 ml min-1 kg-1. After 200 mg twice daily oral treatment steady state was reached within 3-4 days with trough and peak plasma levels on day 8 of 457 and 662 ng ml-1, which are well within the therapeutic range. PMID- 3094569 TI - Valpromide inhibits human epoxide hydrolase. AB - The effect of antipileptic drug valpromide (VPM) on the activity of epoxide hydrolase was studied in human adult and foetal liver, kidneys, lungs, intestine and in placenta. The activity of the epoxide hydrolase was measured with both styrene oxide and benzo(a)pyrene-4,5-oxide as substrates. VPM inhibited the epoxide hydrolase obtained from all organs studied. The degree of inhibition was independent of the substrate used. A lowering of the epoxide hydrolase activity by 50% was observed when the concentration of VPM was similar to that of the substrates. VPM competitively inhibited the activity of adult liver epoxide hydrolase with styrene oxide as substrate. PMID- 3094571 TI - The pharmacokinetics of sodium cromoglycate in man after intravenous and inhalation administration. AB - The pharmacokinetics of sodium cromoglycate in four healthy volunteers after slow intravenous infusion have been evaluated following measurement of plasma concentrations by radioimmunoassay. The results confirm earlier findings that sodium cromoglycate is rapidly eliminated from the body and that the data can be fitted to a two compartment open model. The pharmacokinetic parameters derived from the intravenous administration were used to evaluate the pharmacokinetics after inhalation administration via the Spinhaler. A model for absorption from the lungs is described which involves absorption at two different rates; this gives a better fit to the observed data than a single absorption rate. A fast absorption rate constant with a mean value of 0.54 min-1 and a slower rate constant with a mean value of 0.0097 min-1 were found. Of a mean total of 2.84 mg absorbed from a 20 mg inhaled dose, 0.68 +/- 0.15 (s.e. mean) mg were absorbed at the fast rate and 2.17 +/- 0.37 mg at the slower rate. These rates probably reflect absorption from different sites within the lungs. The results may have important implications for interpretation of clinical findings. PMID- 3094572 TI - Pharmacokinetics of the new benzodiazepine antagonist Ro 15-1788 in man following intravenous and oral administration. AB - During clinical pharmacology studies with the benzodiazepine antagonist Ro 15 1788 the pharmacokinetic characteristics of high intravenous doses (20 and 40 mg) and of an oral dose (200 mg) were examined in six healthy male volunteers. Ro 15 1788 was rapidly and extensively distributed in the body with an apparent volume of distribution Vss of 1.06 l kg-1. Elimination occurred rapidly by hepatic metabolism and the high plasma clearance of 1.14 l min-1 resulted in a short elimination half-life of less than 1 h. No difference in the disposition parameters calculated from the data after the 20 and 40 mg doses was observed reflecting a dose-proportionality in the areas under plasma concentration-time curves and unchanged distribution characteristics. Because the blood/plasma distribution coefficient is close to unity the disposition parameters obtained from plasma concentrations are similar to the corresponding parameters with reference to blood. Following oral administration of 200 mg the drug is rapidly absorbed. Peak levels were reached after 20-90 min and were close to or even higher than the values after the 40 mg intravenous dose at the same time point. Due to the high hepatic extraction ratio the fraction reaching the systemic circulation unchanged was reduced to approximately 16% during the absorption step. PMID- 3094573 TI - Haemolytic disease of the newborn--the changing scene. AB - Between 1950 and 1970 there was a steady decline in the number of infant deaths from rhesus haemolytic disease of the newborn in the Yorkshire Region but no decrease in the number of pregnant women with antibodies. Following the introduction of Rh prophylaxis in 1970, the number of pregnant women sensitized has decreased by 70% and the number of infant deaths by 96%. The number of infants requiring exchange transfusion has also decreased by 70%. During the years 1980 to 1983 there were 163 new cases of maternal sensitization to the D antigen in the Yorkshire Region, 36 were due to failures of administration, 75 were failures of protection and 26 were in primigravidae. Eighteen of the failures of administration occurred after abortion, nine of which were surgical terminations. Antenatal prophylaxis may well have protected 64 (40%) of these 163 women. The number of pregnant women with antibodies other than anti-D now exceeds those with anti-D. The effect of these changes in incidence and clinical severity on the management of Rh D negative pregnant women is discussed. PMID- 3094574 TI - Tyrosinase catalyzes an unusual oxidative decarboxylation of 3,4 dihydroxymandelate. AB - Tyrosinase usually catalyzes the conversion of monophenols to o-diphenols and oxidation of diphenols to the corresponding quinones. However, when 3,4 dihydroxymandelic acid was provided as the substrate, it catalyzed an unusual oxidative decarboxylation reaction generating 3,4-dihydroxybenzaldehyde as the sole product. The identity of the product was confirmed by high-performance liquid chromatography (HPLC) as well as ultraviolet and infrared spectral studies. None of the following enzymes tested catalyzed the new reaction: galactose oxidase, ceruloplasmin, superoxide dismutase, ascorbate oxidase, dopamine beta-hydroxylase, and peroxidase. Phenol oxidase inhibitors such as phenylthiourea, potassium cyanide, and sodium azide inhibited the reaction drastically, suggesting the participation of the active site copper of the enzyme in the catalysis. Mimosine, a well-known competitive inhibitor of tyrosinase, competitively inhibited the new reaction also. 4-Hydroxymandelic acid and 3 methoxy-4-hydroxymandelic acid neither served as substrates nor inhibited the reaction. Putative intermediates such as 3,4-dihydroxybenzyl alcohol and (3,4 dihydroxybenzoyl)formic acid did not accumulate during the reaction. Oxidation to a quinone methide derivative rather than conventional quinone accounts for this unusual oxidative decarboxylation reaction. Earlier from this laboratory, we reported the conversion of 4-alkylcatechols to quinone methides catalyzed by a cuticular phenol oxidase [Sugumaran, M., & Lipke, H. (1983) FEBS Lett. 155, 65 68]. Present studies demonstrate that mushroom tyrosinase will also catalyze quinone methide production with the same active site copper if a suitable substrate such as 3,4-dihydroxymandelic acid is provided. PMID- 3094575 TI - Identification of peptide sequences at the tRNA binding site of Escherichia coli methionyl-tRNA synthetase. AB - Four different structural regions of Escherichia coli tRNAfMet have been covalently coupled to E. coli methionyl-tRNA synthetase (MetRS) by using a tRNA derivative carrying a lysine-reactive cross-linker. We have previously shown that this cross-linking occurs at the tRNA binding site of the enzyme and involves reaction of only a small number of the potentially available lysine residues in the protein [Schulman, L. H., Valenzuela, D., & Pelka, H. (1981) Biochemistry 20, 6018-6023; Valenzuela, D., Leon, O., & Schulman, L. H. (1984) Biochem. Biophys. Res. Commun. 119, 677-684]. In this work, four of the cross-linked peptides have been identified. The tRNA-protein cross-linked complex was digested with trypsin, and the peptides attached to the tRNA were separated from the bulk of the tryptic peptides by anion-exchange chromatography. The tRNA-bound peptides were released by cleavage of the disulfide bond of the cross-linker and separated by reverse phase high-pressure liquid chromatography, yielding five major peaks. Amino acid analysis indicated that four of these peaks contained single peptides. Sequence analysis showed that the peptides were cross-linked to tRNAfMet through lysine residues 402, 439, 465, and 640 in the primary sequence of MetRS. Binding of the tRNA therefore involves interactions with the carboxyl-terminal half of MetRS, while X-ray crystallographic data have shown the ATP binding site to be located in the N-terminal domain of the protein [Zelwer, C., Risler, J. L., & Brunie, S. (1982) J. Mol. Biol. 155, 63-81].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094577 TI - Cholesterol-dependent modification of microsomal dynamics and UDPglucuronyltransferase kinetics. AB - The effect of both in vitro incorporation and removal of cholesterol in guinea pig liver microsomes on the lipid composition, dynamic properties of the membrane, and kinetic constants of UDPglucuronyltransferase was studied. No significant changes either in the fatty acid composition or in the distribution of phospholipid classes were observed upon cholesterol incorporation and removal. Lateral and rotational mobility measured by the efficiency of pyrene excimer formation and fluorescence of 1,6-diphenylhexatriene decreased with cholesterol incorporation and increased in parallel to cholesterol removal. These changes were associated with alterations in the kinetic properties of UDPglucuronyltransferase. Whereas Vmax increased, the Km of the different steps of the reaction decreased with cholesterol incorporation. The negative homotropic effect and apparent cooperativity of UDP-glucuronic acid decreased when cholesterol was incorporated and increased after cholesterol removal. Moreover, the UDP-N-acetylglucosamine-dependent activation of the enzyme decreased in correlation with an increase of cholesterol concentration in microsomes. It has been demonstrated that both the shift of the non-Michaelian kinetics of the enzyme to Michaelian and the decrease of the UDP-N-acetylglucosamine-dependent activation of the enzyme are evoked by a change of the physical state of the UDPglucuronyltransferase milieu from a gel phase to a liquid-crystalline phase. Therefore, we must admit that cholesterol incorporation in the microsomes while producing an increased packing of the bulk lipids would also cause the separation of more fluid phospholipids, which increase the proportion of molecules in the liquid-crystalline state within the enzyme environment. PMID- 3094576 TI - Native state of high mobility group chromosomal proteins 1 and 2 is rapidly lost by oxidation of sulfhydryl groups during storage. AB - Oxidized forms of non-histone chromosomal proteins high mobility group 1 (HMG1) and HMG2 were detected by high-pressure liquid chromatography of preparations stored at 4 degrees C for 1 day. The oxidized form of each was found to have two free sulfhydryl groups, while the freshly prepared native form of each contained four. The native, reduced state could be maintained during storage by the addition of ethylenediaminetetraacetic acid or reducing agents. PMID- 3094578 TI - Self-association and phospholipid binding properties of iodinated apolipoprotein A-I. AB - Kinetic turnover studies of apolipoprotein metabolism often utilize radioiodinated tracers. These studies rely on the "tracer assumption" that the modified tracer is physiologically and metabolically identical with the native unmodified tracer. This paper addresses the validity of this assumption on the basis of the examination of the state of self-association and binding properties with egg yolk phosphatidylcholine small unilamellar vesicles of native and iodinated apolipoprotein A-I (apoA-I). Human apoA-I was iodinated to the extent of 1.0 and 3.7 mol of nonradioactive iodine/mol of protein. At concentrations from 0.013 to 0.8 mg/mL, iodinated apoA-I underwent concentration-dependent self association similar to that of native apoA-I as evidenced by circular dichroism and gel filtration. At all concentrations, however, the iodinated preparations were more highly self-associated as judged by gel filtration in relation to the extent of iodination. Scatchard analysis of fluorometric titrations of apoA I/vesicle interactions demonstrated that the binding capacity of vesicles for apoA-I increased and apoA-I binding affinity decreased upon iodination. In addition, the kinetics of apoA-I binding to vesicles was enhanced by iodination. The affinity, capacity, and kinetics of apoA-I binding were each altered 2-3-fold dependent on the extent of iodination. Since the dynamic interactions of apoA-I are perturbed by iodination, one may legitimately question whether the "tracer assumption" is valid for 125I-apoA-I under all experimental conditions. PMID- 3094579 TI - Structural and functional differences between the two intrinsic zinc ions of Escherichia coli RNA polymerase. AB - DNA-dependent RNA polymerase (RPase) from Escherichia coli contains 2 mol of intrinsic Zn(II)/mol of core enzyme (alpha 2 beta beta'). In techniques analogous to those employed with the Zn(II) metalloenzyme aspartate transcarbamoylase [Hunt, J. B., Neece, S. H., Schachman, H. K., & Ginsberg, A. (1984) J. Biol. Chem. 259, 14793-14803], we show that titration of core or holoRPase with 10 or 16 equiv, respectively, of the sulfhydryl reagent p (hydroxymercuri)benzenesulfonate (PMPS) results in the facile release of 1 mol of Zn(II) [B-site Zn(II)] in a reaction totally reversible with the addition of excess thiol provided no metal chelator is present. If ethylenediaminetetraacetic acid (EDTA) is present, reversal of the PMPS-enzyme complex results in formation of a Zn1 RPase [A-site Zn(II)]. This enzyme retains full transcriptional activity relative to Zn2 RPase on both calf thymus (nonspecific) and T7 (sigma-dependent, specific) DNA templates. If the core enzyme-PMPS complex is incubated with a large excess of another metal such as Cd(II) followed by thiol treatment, a hybrid ZnACdB RPase is formed. Direct treatment of the enzyme with excess Cd(II) also gives rise to a hybrid ZnACdB RPase. Transcription by these enzymes is also comparable to that of the starting Zn2 enzyme. Isolation of in vivo synthesized Co2 RPase and Cd2 RPase and treatment of either enzyme with PMPS/EDTA results in formation of a CoA and CdA enzyme, respectively. Co(II)A and Cd(II)A enzymes show 123 and 76%, respectively, of the elongation rates on T7 DNA observed for the Zn(II) enzyme. Visible absorption spectroscopy of the Co2 enzyme exhibits four d d transition bands positioned at 760 (epsilon = 800), 710 (epsilon = 900), 602 (epsilon = 1500), and 484 (epsilon = 4000) nm. In addition, two charge-transfer bands are found at 350 (epsilon = 9600) and 370 (epsilon = 9500) nm. Only the Co(II) ion bound at site A is associated with this unique set of intense d-d transitions. The positions and intensities of both the visible and charge transfer bands of Co(II)A RPase approximate those shown by Co(II)-substituted metalloenzyme sites where the ligands are four S rather than mixed S,N or S,O sites. PMID- 3094580 TI - Identification and assignment of base pairs in three helical stems of Torulopsis utilis ribosomal 5S RNA and its RNase T1 and RNase T2 cleaved fragments via 500 MHz proton homonuclear overhauser enhancements. AB - Imino proton resonances in the downfield region (10-14 ppm) of the 500-MHz 1H NMR spectrum of Torulopsis utilis 5S RNA are identified (A X U, G X C, or G X U) and assigned to base pairs in helices I, IV, and V via analysis of homonuclear Overhauser enhancements (NOE) from intact T. utilis 5S RNA, its RNase T1 and RNase T2 digested fragments, and a second yeast (Saccharomyces cerevisiae) 5S RNA whose nucleotide sequence differs at only six residues from that of T. utilis 5S RNA. The near-identical chemical shifts and NOE behavior of most of the common peaks from these four RNAs strongly suggest that helices I, IV, and V retain the same conformation after RNase digestion and that both T. utilis and S. cerevisiae 5S RNAs share a common secondary and tertiary structure. Of the four G X U base pairs identified in the intact 5S RNA, two are assigned to the terminal stem (helix I) and the other two to helices IV and V. Seven of the nine base pairs of the terminal stem have been assigned. Our experimental demonstration of a G X U base pair in helix V supports the 5S RNA secondary structural model of Luehrsen and Fox [Luehrsen, K. R., & Fox, G.E. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 2150-2154]. Finally, the base-pair proton peak assigned to the terminal G X U in helix V of the RNase T2 cleaved fragment is shifted downfield from that in the intact 5S RNA, suggesting that helices I and V may be coaxial in intact T. utilis 5S RNA. PMID- 3094581 TI - Characteristics of lysine uptake by isolated renal cortical tubule fragments from mature and immature dogs. AB - The uptake of L-lysine was examined in isolated renal cortical tubule fragments from adult and 1-week-old dogs. Lysine uptake by adult tubules was initially more rapid than that by the immature tubules. This uptake by mature tubules reached a steady state after 30 min of incubation, while the newborn tubules still had not reached a steady state by 90 min of incubation. Because a steady state of lysine uptake was not attained with the immature tubules, their uptake of lysine exceeded that of the adult after 60 min of incubation. Kinetic studies revealed that lysine was taken up by one saturable transport system with a Km of 0.56 mM and Vmax of 6.18 mmol/liter intercellular fluid per 5 min in the adult and one saturable transport system in the 1-week-old with a Km of 0.38 mM and Vmax of 3.66 mmol/l intracellular fluid per 5 min. Lysine also entered the renal tubule cells in both age groups via a diffusional pathway with a kd of 0.35 min-1 in the adult and 0.30 min-1 in the newborn. Cystine competitively inhibited lysine uptake by adult dog tubules with a Ki of 0.61 mM. The other dibasic amino acids, ornithine and arginine, also inhibited lysine uptake in both the adult and the newborn. PMID- 3094582 TI - Direct characterization of influenza viral NS1 mRNA and related sequences from infected HeLa cells and a cell-free transcription system. AB - The NS1 mRNA of the influenza A virus WSN (H0N1) strain was isolated from a cell free transcription system, and from the cytoplasm of virus-infected HeLa cells. The 32P-labeled NS1 mRNA derived from the infected cell cytoplasm was characterized by the secondary enzymatic analysis of sixteen of its large or distinct RNAase T1-resistant oligonucleotides. Several WSN strain-specific nucleotide differences from the previously-determined sequence of NS1 mRNA from the PR8 (H0N1) strain of influenza A virus, were located within these sequences. The RNAase T1-resistant oligonucleotides were placed within the primary sequence of NS1 mRNA, using the PR8 strain sequence data. The resulting linear map was then used to identify NS2 mRNA isolated from the infected cell cytoplasm, and an NS-related RNA species generated from NS1 mRNA incubated in a HeLa cell-free extract. PMID- 3094583 TI - Quantitative determination of apolipoprotein A-I in high-density lipoproteins and 'free' apolipoprotein A-I by two-dimensional agarose gel lipoprotein-'rocket' immunoelectrophoresis of human serum. AB - A method has been developed for quantitative analysis of 'free' apolipoprotein A I and apolipoprotein A-I associated with high-density lipoprotein (HDL) in serum. The method utilizes the difference between the rate of electrophoretic migration of apolipoprotein A-I associated with HDL (alpha) and 'free' apolipoprotein A-I (pre-beta) in agarose gel. Apolipoprotein A-I is subsequently quantitated by electrophoresis in a second dimensional gel containing anti-apolipoprotein A-I antibodies. Using this method all apolipoprotein A-I of normal fasting serum was found associated with HDL (n = 16). By contrast, 'free' apolipoprotein A-I accounted for up to 12% of the total in the serum of patients with isolated hypertriglyceridemia (n = 8) or mixed hyperlipoproteinemia (n = 8). Between 30 and 35% of 'free' apolipoprotein A-I was found in one patient afflicted with the apolipoprotein C-II deficiency syndrome. Also, 'free' apolipoprotein A-I could be detected in normal postabsorptive serum. 30 and 90 min following heparin-enhanced lipolysis 'free' apolipoprotein A-I accounted for 23 and 20%, respectively, of the total apolipoprotein A-I of serum. Apolipoprotein A-I associated with HDL remained unaltered. It appears, therefore, that 'free' apolipoprotein A-I is liberated from triglyceride-rich lipoproteins during lipolysis. PMID- 3094584 TI - Competitive inhibitors of rabbit hepatic microsomal steroid 12 alpha-hydroxylase. AB - The sterols 7 alpha-hydroxycholest-4-en-3-one (I) and 5 alpha-cholestane-3 alpha,7 alpha-diol (II) are competitive inhibitors for rabbit hepatic microsomal preparations of steroid 12 alpha-hydroxylase with apparent Ki values of 56 and 93 microM, respectively. To ascertain the optimum structure for a substrate with maximal enzymic activity, nine sterols or steroidal acids containing the 7 alpha hydroxy-4-en-3-one or 3 alpha,7 alpha-dihydroxy-5 alpha configuration were prepared and studied as inhibitors with enzyme preparations in the presence of NADPH, oxygen and appropriate cofactors. Although each of these compounds exhibited competitive inhibition, the best inhibitor for sterol (I) was 7 alpha,25-dihydroxycholest-4-en-3-one (IV) (Ki 36 microM). Steroidal acids (3-oxo 7 alpha-hydroxychol-4-enoic acid and 3-oxo-7 alpha-hydroxy-4-cholene-24 carboxylic acid) were poor inhibitors (Ki 1080 and 654 microM, respectively). For sterol (II) the best inhibitors were sterol (IV) (Ki 35 microM) and 5 alpha cholestane-3 alpha,7 alpha,25-triol (VIII) (Ki 45 microM). The 12 alpha hydroxylated products of sterols (I) and (IV) were less tightly bound to the enzyme (Ki 88 and 98 microM, respectively) in the presence of sterol (II). Allochenodeoxycholic acid (Ki 495 microM) was not a good inhibitor for sterol (II). 12 alpha-Hydroxylated products of sterols (IV) and (VIII) were isolated from larger scale incubations, separated by HPLC and identified by mass spectrometry. PMID- 3094585 TI - Metabolism of galactosylceramide in the twitcher mouse, an animal model of human globoid cell leukodystrophy. AB - The metabolism of galactosylceramide was investigated in normal and twitcher mice, an animal model for human globoid cell leukodystrophy. The findings were compared with data obtained on human tissues. In vitro studies demonstrated that there were two genetically distinct enzymes that hydrolyze galactosylceramide: galactosylceramidase I and II. The former was deficient in the twitcher, while the latter was intact. beta-Galactosidase preparations purified from normal mouse liver possessed the activity to hydrolyze galactosylceramide when the assay conditions for galactosylceramidase II was used. Therefore, galactosylceramidase II was considered to be identical to GM1 ganglioside beta-galactosidase. In contrast to the human enzyme, the murine beta-galactosidase had a relatively high Km value toward galactosylceramide. The galactosylceramide-loading test demonstrated that the twitcher fibroblasts hydrolyzed the lipid at lower rates than seen in cases of human globoid cell leukodystrophy fibroblasts. These differences in galactosylceramidase II between murine and human tissues suggest that galactosylceramide accumulates in twitcher mice but not in humans with globoid cell leukodystrophy, even though galactosylceramidase I is genetically deficient in both human and this mouse model. PMID- 3094587 TI - Glycosylation of human thyroglobulin and characterization by lectin affinity electrophoresis. AB - Thyroglobulin, a 660 kDa glycoprotein, is the major product of protein synthesis in the thyroid gland. It has been suggested that modifications of thyroglobulin glycosylation occur in various thyroid disorders. In order to study possible changes in glycosylation of tissue thyroglobulin associated with thyroid disease, we have developed a lectin affinity electrophoresis system which allows characterization of small (less than 1 microgram) quantities of thyroglobulin. Human thyroglobulin was extracted and purified. Agarose gels were cast containing concanavalin A, Ricinus communis agglutinin, L-phytohaemagglutinin and pokeweed mitogen at various concentrations. Purified human thyroglobulin was serially diluted, loaded onto lectin gels and electrophoresed. Concanavalin A, R. communis agglutinin and phytohaemagglutinin all bound thyroglobulin in a concentration dependent manner. Pokeweed mitogen did not bind thyroglobulin. Purified thyroglobulin was treated with neuraminidase and endoglycosidase H. Two dimensional immunoelectrophoresis revealed the migration of thyroglobulin to be modified by neuraminidase but not by endoglycosidase H. Lectin affinity electrophoresis of purified human thyroglobulin with and without enzyme treatment indicated the presence of: oligomannose structures as shown by concanavalin A reactivity and modification by endoglycosidase H, and complex oligosaccharides as shown by affinity for R. communis agglutinin and modification by neuraminidase. These structures are in keeping with the proposed patterns of glycosylation of human thyroglobulin and indicate suitability of the method for characterizing the glycosylation of small quantities of thyroglobulin. PMID- 3094586 TI - Changes in mucus glycoprotein synthesized in rat gastric mucosa exposed to ethanol. AB - The resistance to proteolysis by pepsin of gastric mucus glycoprotein synthesized by tissue culture in the presence and absence of 0.1 M ethanol was investigated. The glycoprotein product of ethanol-supplemented culture was found to contain 68% less associated lipids and 81% less covalently bound fatty acids, but exhibited unaltered content of carbohydrate and protein. The lipid and fatty acyl deficient glycoprotein was 5-times more rapidly and 2-3-times more extensively degraded by pepsin than the glycoprotein synthesized in the absence of ethanol. Following delipidation with organic solvents and deacylation with hydroxylamine both glycoproteins were digested at the same rate and degraded to the same extent. The lower content of fatty acyl residues markedly affected the overall pattern of the proteolytic fragments identified by SDS gel electrophoresis. The peptides corresponding to the acylated fragments of control were degraded and an increase in the amount of smaller peptides was observed. The in vitro assays of the fatty acyltransferase activity towards the substrates obtained from control and alcohol containing cultures revealed that the enzyme activity was similar and increased proportionally with increased concentration of both glycoprotein substrates and enzyme. However, addition of 0.1 M ethanol to the assay tubes containing complete incubation mixture decreased the acylation of either glycoprotein by 40%. Based on the results presented here, and on previous studies of mucus glycoprotein synthesis in the presence of ethanol, we conclude that ethanol interferes with the process of acylation of mucus glycoprotein with fatty acids. PMID- 3094588 TI - Acetyltransferase activity in human platelet microsomes and washed platelets. AB - It has been demonstrated that human platelets form platelet-activating factor (PAF) when stimulated by thrombin, collagen and ionophore A-23187, but the mechanism of its formation has not been elucidated. In this study we demonstrated increased acetyltransferase activity (i.e., transfer of the acetyl moiety of [3H]acetyl-CoA to lyso-PAF (1-alkyl-sn-glycero-3-phosphocholine) to form PAF) occurring in human platelet microsomes made from platelets stimulated by thrombin or ionophore A-23187. This stimulation resulted in a 2-4-fold increase in acetyltransferase activity over unstimulated platelets. Acetyltransferase activity was also demonstrated by incubating [3H]acetate with whole platelets and stimulating with thrombin or ionophore A-23187. Radioactive PAF was detected when the platelets were stimulated. None was formed without stimulation. These findings indicate that acetyltransferase may play a role in the biosynthesis of PAF by human platelets. PMID- 3094589 TI - Purification and characterization of rat urinary esterase A1. AB - An enzyme, esterase A1, which hydrolyzes tosyl-arginine methyl ester (Tos-Arg OMe) was separated from esterase A2 and kallikrein of male rat urine and purified by a procedure involving ammonium sulfate fractionation, ion exchange chromatography, hydrophobic chromatography and gel filtration. The resulting preparation was apparently homogeneous, as assessed by polyacrylamide gel electrophoresis. The molecular weight of the preparation was estimated to be 27,000 by SDS-polyacrylamide gel electrophoresis and 30,000 by gel filtration. The enzyme was more specific for arginine methyl esters than for lysine methyl esters. The optimum pH determined with Tos-Arg-OMe as a substrate was 8.0 and the Km was 11.8 mM. The Tos-Arg-OMe esterolytic activity of esterase A1 was inhibited by soybean trypsin inhibitor, but not by aprotinin. In immunodiffusion analysis, the antiserum to esterase A1 formed immunoprecipitin arcs with this enzyme and the urine collected from rat bladder, but not with esterase A2, kallikrein, plasma and the urine collected from ureters. These results indicate that rat urinary esterase A1 differs from esterase A2 and kallikrein. The esterase A1 appears to be produced by accessory sex glands and excreted via the spermiduct into the urine. PMID- 3094590 TI - [Kinetic characteristics of the activation of various structural forms of plasminogen by tissue activator in the presence of fibrin]. AB - It was shown that activation of two native plasminogen and miniplasminogen forms by the tissue activator in the presence of fibrin obeys the Michaelis-Menten kinetics. The kinetic parameters of activation of both plasminogen native forms differ insignificantly. For miniplasminogen whose molecule contains no lysine binding sites, a marked decrease of activation power was observed. The Km value of activator for miniplasminogen is 10 times that of plasminogen form I and 20 times that of plasminogen form II. The kcat/Km value of activator for miniplasminogen is 7 times less than that of plasminogen form I and by one order of magnitude more than that of plasminogen form II. These results testify to the importance of lysine-binding sites in the native plasminogen molecule during the activation of fibrinolysis by the major physiological activator. PMID- 3094591 TI - [Isolation and properties of prostaglandin H synthetase immobilized in insoluble polyelectrolyte complexes]. AB - Immobilization of prostaglandin-H-synthetase (EC 1.14.99.1) of the microsomal fraction of ram vesicular gland in the microparticles of insoluble polyelectrolyte complexes by non-covalent incorporation was studied. It was shown that immobilization occurs with a high efficiency and high activity yield (40 70%). Non-specific reversible inhibition of the enzyme by the polycationic component of the complex was demonstrated. The dependencies of activity of the native and immobilized enzymes on pH, temperature and substrate (adrenaline and arachidonic acid) were studied. The immobilized enzyme had an increased thermal stability as compared to the native one; the thermoinactivation rate constant was decreased 3-7 times. The biexponential type of the curve of the rependence of activity vs. time for the native enzyme and the transformation of the curve into a simple exponential form for the immobilized enzyme were observed. PMID- 3094592 TI - [The presence of glycogen synthase in phosphorylase kinase preparations isolated from rabbit skeletal muscles]. AB - Phosphorylase kinase isolated from rabbit skeletal muscle contains a protein whose molecular mass as determined by polyacrylamide gel electrophoresis is 571 000 Da. The protein was found to possess a higher affinity for glycogen as compared to phosphorylase kinase and phosphorylase. The protein separated from kinase by chromatography on a DEAE-cellulose column produced during SDS electrophoresis one protein band corresponding to Mr of 95 200 Da. The above properties of the protein and the glycogen synthetase activity revealed in the presence of glucose-6-phosphate suggest that phosphorylase kinase preparations contain a hexameric form of glycogen synthetase. PMID- 3094593 TI - Rapid cessation of estrous cyclicity and depressed castration response in short photoperiod-treated, inbred LSH/SsLaK hamsters. AB - This study examined the effects of transfer from long photoperiod (LP) to short photoperiod (SP) on the cessation of ovarian cyclicity and the castration response in inbred LSH/SsLak golden Syrian hamsters. Forty-six 8 to 10-wk-old female hamsters were acclimatized in LP (14L:10D; lights on at 0600 h) during which time animals were monitored for regular ovarian cyclicity. Twenty-six animals were transferred to SP (8L:16D; lights on at 0600 h) and examined daily for vaginal discharges. One day after the day of the first missed ovulation, individual SP-exposed animals were bilaterally ovariectomized; concomitantly, an LP control animal in diestrus I underwent the same procedure. Thirty days after ovariectomy, the hamsters were fitted with intra-atrial silastic cannulae. On the following two postoperative days, 0.6 ml blood samples were collected at 0700, 1200, 1400, and 1600 h for SP animals and at 0700, 1400, 1600 and 1800 h for LP controls. On the third day, the animals were decapitated and sera and pituitaries saved for determination of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) by radioimmunoassay (RIA). All SP-exposed animals displayed their last estrous discharge 14-34 days after transfer to SP (mean = 23.0 +/- 0.8 days). Their ovaries were characterized by the absence of corpora lutea, the presence of large atretic antral follicles, few growing follicles, and interstitium that was stimulated to varying degrees. Total and adjusted pituitary weights were decreased by SP exposure (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094594 TI - Deceleration of age-associated changes in the preovulatory but not secondary follicle-stimulating hormone surge by progesterone. AB - Recently, it has been reported that mating can delay the age-associated decline in reproductive function of female rats. Since circulating progesterone (P) levels are elevated for a 2- to 3-wk interval during pregnancy, the following study was conducted to determine whether intermittent elevation in P levels can alter the rate of reproductive aging in female rats. Beginning at 2 mo of age, 4 day-cycling, virgin rats were divided into two groups. In one group, 3 Silastic capsules containing crystalline P were inserted s.c. into each rat while rats in another group each received 1 empty capsule. After 2 wk, the capsules were removed for 2 wk. Thereafter, implantation and removal of capsules was repeated 5 additional times. Rats receiving P capsules became acyclic 3-4 days after exposure to P and resumed cyclicity 4-7 days after removal of P-capsules. One month after the last series of capsules was removed (rats approximately 8-mo old), rats exhibiting consecutive 4-day cycles were inserted with indwelling atrial cannulae and bled at 4-h intervals from 1400 h on proestrus (Pr) to 1000 h on estrus (E). At 1600 h E, rats were killed and trunk blood was collected. For comparison, a group of 3-mo-old (young) rats was bled on Pr and E. In 8-mo-old rats that received empty capsules, 27% exhibited 4-day cycles compared to 66% of the young rats. However, in contrast to rats that received empty capsules, 63.1% of P-treated rats exhibited 4-day cycles. Surges of preovulatory luteinizing hormone (LH) and follicle-stimulating hormone (FSH) surges were attenuated in 8 mo-old rats given empty capsules compared to young rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094595 TI - Circadian and photoperiodic effects of brief light pulses in male Djungarian hamsters. AB - The effects of brief light pulses (1-60 min in duration) on the circadian rhythm of locomotor activity and/or the neuroendocrine-gonadal axis was investigated in male Djungarian hamsters. Exposure of hamsters free-running in constant darkness to a single 1-h pulse of light induced phase-dependent phase shifts in the rhythm of locomotor activity. The general shape of the "phase-response curve" was similar to that observed in other animals; phase-delays and phase-advances were induced by light pulses delivered in the early and late subjective night, respectively, while light pulses during the subjective day induced little or no phase-shift in the activity rhythm. Animals exposed for 7 days to 1-min of light during the night in animals otherwise exposed to 6L:18D resulted in increased levels of serum FSH and testicular weight. Daily exposure to two 1-h or two 10 min pulses of light (but not two 1-min pulses) for 10 days resulted in stable entrainment of the activity rhythm as well as testicular weight gains and serum FSH increases. When two 10-min pulses of light were presented 8 and 16 h apart, some animals showed a short-day entrainment pattern (i.e., locomotor activity confined to the long period of darkness) while other animals showed a long-day entrainment pattern (i.e., locomotor activity confined to the short period of darkness). Importantly, the stimulatory effects of light on neuroendocrine gonadal activity were clearly dependent on the phase-relationship between the light pulses and the circadian rhythm of locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094596 TI - Active immunization of intact mares against gonadotropin-releasing hormone: differential effects on secretion of luteinizing hormone and follicle-stimulating hormone. AB - Five lighthorse mares were actively immunized against gonadotropin releasing hormone (GnRH) to determine the relative importance of this hypothalamic hormone in the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Five mares immunized against the conjugation protein served as controls. Mares were initially immunized in November and received secondary immunizations 4 wk later, and then at 6-wk intervals until ovariectomy in June. All mares immunized against GnRH exhibited an increase (p less than 0.01) in the binding of tritiated GnRH by plasma, an indication that antibodies against this hormone had been elicited. Concentrations of LH, FSH and progesterone in weekly blood samples were lower (p less than 0.05) in GnRH-immunized mares than in controls after approximately 4 mo of immunization. However, the LH concentrations were affected to a greater degree than were FSH concentrations. All five control mares exhibited normal cycles of estrus and diestrus in spring, whereas no GnRH immunized mare exhibited cyclic displays of estrus up to ovariectomy. All mares were injected intravenously with a GnRH analog (which cross-reacted less than 0.1% with the anti-GnRH antibodies) in May, after all control mares had displayed normal estrous cycles, to characterize the response of LH and FSH in these mares; two days later, the mares were injected with GnRH. The LH response to the analog, which was assessed by net area under the curve, was lower (p less than 0.01) by approximately 99% in mares immunized against GnRH than in control mares. In contrast, the FSH response to the analog was similar for both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094597 TI - Gonadotrope function in ovariectomized ewes actively immunized against gonadotropin-releasing hormone (GnRH). AB - The gonadotrope cells of the ovine anterior pituitary were insulated from hypothalamic inputs by imposing an immunologic barrier generated by active immunization of ovariectomized ewes against gonadotropin-releasing hormone (GnRH) conjugated to keyhole limpet hemocyanin (KLH) through a p-aminophenylacetic acid bridge. All GnRH-KLH animals immunized developed titers of anti-GnRH that exceeded 1:5000. The antisera were specific for GnRH and cross-reacted with GnRH agonists modified in position 10 to an extent that was less than 0.01%. Ewes actively immunized against GnRH-KLH displayed levels of basal and GnRH agonist induced gonadotropin secretion that were markedly lower (p less than 0.05) than comparable parameters in ewes actively immunized against KLH. In contrast, basal and thyrotropin-releasing hormone (TRH)-induced prolactin (PRL) secretion were not compromised by active immunization. Immunization against the GnRH-KLH conjugate, but not KLH alone, prevented expression of the positive feedback response to exogenous estradiol (E2). Pituitary stores of immunoactive luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were significantly (p less than 0.001) reduced in ewes immunized against GnRH-KLH but stores of PRL were not affected by such immunization. Further, the biopotency of the residual LH stores in tissue of animals from the anti-GnRH group was significantly (p less than 0.05) lower than LH biopotency in anti-KLH animals. Serum levels of LH in anti-GnRH ewes were restored by circhoral administration of a GnRH agonist that did not cross-react with the antisera generated. Pulsatile delivery of GnRH agonist in anti-GnRH ewes significantly (p less than 0.05) elevated serum LH within 48 h and reestablished LH levels comparable to anti-KLH ewes within 6 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094598 TI - Quantification and partial characterization of the hamster sperm proacrosin acrosin system. AB - The proacrosin-acrosin proteinase system was measured and partially characterized in unpurified extracts of washed hamster epididymal sperm. Autoactivation experiments demonstrated that proacrosin accounted for greater than 98% of the acrosin activity in the sperm extracts from individual animals. Several bands of proteinase activity were observed on gelatin-sodium dodecyl sulfate polyacrylamide gel electrophoretic (gelatin-SDS-PAGE) zymography. The major proteinase activities in the nonactivated extracts corresponded to relative molecular masses (Mr) of 51,000 to 56,000, while less distinct digestion occurred with relative molecular masses of 37,000 to 49,000. It was demonstrated that after a serial dilution of the sperm extract, the proteinase activity in as few as 6,000 sperm could readily be detected by the gelatin-SDS-PAGE methods. Time course activation studies showed that the zymogen was completely converted to active proteinase in 45-60 min at pH 8.0 and 25 degrees C. This autoconversion process was markedly inhibited by calcium, sodium, and heparin. However, each of these compounds stimulated the proteolytic activity of acrosin. These studies demonstrate that the proacrosin-acrosin system can be investigated in extracts of nonpurified hamster epididymal sperm. PMID- 3094599 TI - Charge redistribution in proteins via linear hydrogen-bond chains. AB - It is proposed that proteins might activate specific atomic positions within bound substrates or co-factors by means of hydrogen-bond chains. As a result of a concerted proton (tautomeric) shift in the linked residues of the hydrogen-bond chain, which includes the bound molecule, a charge separation occurs. The charge thus generated at a specific atom of the bound molecule renders it nucleophilic or electrophilic, as the case may be, and hence 'activated' towards subsequent chemical events. To test the feasibility of the theory a survey of published X ray diffraction determined structures was performed. A search was made for hydrogen-bond chains which emanate away from bound substrates, co-factors or metal ions in order to validate the existence of such structural arrangements. Secondly, an attempt was made to incorporate the proposed proton dynamics into the proteins' mechanisms of action. Examples in which these criteria were satisfied are carboxypeptidase A, carbonic anhydrase, haemoglobin, dihydrofolate reductase, glutathione reductase and p-hydroxybenzoate hydroxylase. PMID- 3094600 TI - Detection of TRH extended peptides in rat hypothalamus using an antibody raised to pGluHisProGlyLys. AB - An antibody was raised to the synthetic pentapeptide pGluHisProGlyLys which, in radioimmunoassay (RIA), could detect the pentapeptide at a level of 10 fmole per tube and exhibited less than 0.5 per cent cross reactivity with a series of related peptides. The RIA was used to demonstrate the presence of C-terminally extended forms of thyrotropin releasing hormone (TRH) in rat hypothalamus. After extraction, the endogenous peptides were resolved by gel exclusion chromatography and TRH-extended peptides were revealed by trypsin digestion to release the pentapeptide. The TRH extended peptides occurred in substantial quantity, approximately 11 pmoles/g, indicating that only partial processing of the gene duplicated prohormone takes place. PMID- 3094601 TI - Dietary modulation of retina phospholipids and photoreceptor function with particular reference to phosphatidylinositol. AB - The effect of dietary partially hydrogenated herring oil (HHO) on the fatty acid composition of the phospholipids of rat retina and on the amplitude of the a-wave of the electroretinogram (ERG) was studied in rats raised for several generations on an essential fatty acid poor diet. The most significant effect of the dietary treatment was a decreased content of arachidonic acid (C20:4 omega 6) and an increased concentration of docosahexaenoic acid (C22:6 omega 2) and 18:1 isomers associated with the phosphatidylinositol (PI). The a-wave of the ERG showed a decreasing amplitude during the experiment and was reduced with about 30% (P less than 0.004) of the initial value in all rats at the end of the experiment. The pronounced change in the arachidonic content in PI and the decreased amplitude of the a-wave of the ERG suggest that arachidonic acid of the PI has an important function in the visual phototransduction process. PMID- 3094602 TI - [Hemoglobin polymers during their circulation in the vascular bed of animals]. AB - The effect of molecular mass of 1 g/kg hemoglobin (Hb) modified by glutaraldehyde and pyridoxal-5'-phosphate on the duration of Hb presence in the rabbit circulation was studied. Hb concentration and met-form content were measured in plasma samples taken 5 min, 6, 18 and 24 h after the injection. Gel and ion exchange chromatography was performed. Predominant clearance of low-molecular fractions within the first 6 h of circulation was shown, it was followed by a rise in high-molecular fraction (greater than 300,000) content, that might be caused by the interaction of modified Hb with plasma proteins. This corroborates the decrease in the overall charge of the circulating fractions. PMID- 3094603 TI - Acute lymphoblastic leukemia and non-Hodgkin's lymphoma of T lineage: colony forming cells retain growth factor (interleukin 2) dependence. AB - The regulatory role of interleukin 2 (IL 2) in the proliferation of T acute lymphoblastic leukemia (T-ALL) and T non-Hodgkin's lymphoma (T-NHL) cells from six individual patients was analyzed in a colony culture system to which pure recombinant IL 2, and the lectin phytohemagglutinin (PHA) or the phorbol ester 12 O-tetradecanoyl phorbol-13-acetate (TPA), had been added. The proliferative response was correlated with the inducibility of receptors for IL 2 on the surface membrane of T-ALL and T-NHL cells by incubation with TPA or PHA for 18 hours. Leukemic T cell colonies, identified by immunophenotyping or cytogenetic analysis, appeared in vitro following TPA and IL 2 stimulation in all six cases. Accordingly, receptors for IL 2, initially absent from the cell surface, were found on high proportions of the T-ALL and T-NHL cells after in vitro exposure to TPA. In contrast, colony formation stimulated by PHA and the induction of IL 2 receptors by PHA were limited to the one case of T-NHL with the mature thymocyte immunophenotype. The cells from the other patients, expressing common or prothymocyte phenotypes, did not respond to PHA. No colonies were formed in any of these cases when PHA or TPA was withheld from the IL 2-containing cultures. Although colony growth depended absolutely on exogenous IL 2 in three cases (ALL), in the three other cases (one ALL, two NHL) some colonies grew also when no IL 2 had been added to the cultures. Upon further analysis of the cells of one of the latter patients, it was found that the cells produced IL 2 and proliferated in response to this endogenous IL 2. The results from this study indicate that the requirements of endogenous v exogenous IL 2 for cell proliferation in T-ALL and T-NHL and IL 2 receptor activation by PHA and TPA vary from patient to patient. In addition, they support the notion that T-ALL and T NHL cells have not lost dependence on IL 2 and IL 2 receptor activation for in vitro growth. PMID- 3094605 TI - Carryover of aflatoxin B1 in contaminated substrate corn into Nigerian native beer. PMID- 3094604 TI - Divergent molecular phenotypes of KG1 and KG1a myeloid cell lines. AB - The cell line KG1 derived from a patient with erythroleukemia in myeloblastic relapse has the composite phenotype and functional repertoire of myeloblasts. In marked contrast, its subline KG1a has lost myeloid features, acquired new karyotypic markers, and has three characteristics associated with immature T cells: low-level expression of the T cell receptor beta mRNA (but not alpha) transcribed from a germline gene; high-level expression of T3 delta mRNA and intracellular, but not cell surface, T3 protein; and expression of the CD7/gp40 T cell-associated membrane antigen. Both KG1 and KG1a transcribe unrearranged IgH genes. These data suggest that either the KG1 cell line was derived from a common myeloid-lymphoid progenitor or that the KG1a subline phenotype is aberrant. PMID- 3094606 TI - Cold air test: a simplified standard method for airway reactivity. AB - A simple and standardized test has been developed to measure airway responsiveness to cold dry air. This consists of stepwise increases in ventilation of dry subfreezing air at 10, 20, 40 and 60% of predicted indirect maximum breathing capacity (IMBC). For each step, the inhalation time was 3 min. The optimal time between the steps was 5 min. Exposure ceased when either a fall in forced expiratory volume in one second (FEV1) of more than 20% of baseline occurred or when there was no response after breathing cold air at 60% predicted IMBC. Moderate isocapnic hyperventilation with cold air beyond 3 min induced no further bronchoconstriction. Varying the interval (0, 2 and 5 min) between the steps produced no significant differences in test results. Changing the pattern of breathing had no effect on airway responsiveness, provided that the patient maintained a constant minute-ventilation. This implies that it is not necessary to monitor the rate and depth of respiration continuously in order to achieve a given minute-ventilation, making the technique simpler. In addition, a "CO2 requirement graph" has been constructed at different levels of ventilation. This allows the inspired CO2 concentration to be preset, eliminating the need for elaborate equipment and monitoring of end-tidal CO2 to keep the subject isocapnic during hyperventilation. PMID- 3094607 TI - Functional and immunoreactive alpha 1 proteinase inhibitor in bronchoalveolar lavages: methodological studies. AB - The functional activity of alpha 1 proteinase inhibitor (alpha 1PI) in bronchoalveolar lavages (BAL) was determined with an automated method, using its inhibitory capacity against porcine pancreatic elastase. Immunoreactive alpha 1PI was measured by immunonephelometry-laser (INL). These two methods may generally be applied on unconcentrated samples. Precision and accuracy of both methods are studied. INL was preferably used to electroimmunodiffusion (EID) because it gave unchanged values after alpha 1PI had reacted with proteases. In BAL, for some specimens, the alpha 1PI content evaluated by EID was underestimated with respect to its measurement by INL. The degree of underestimation is related to the presence of non-functional forms of alpha 1PI. PMID- 3094608 TI - Haemodynamic, gasometric and haematological effects of air infusion in dogs: leukotriene inhibition with U-60,257. AB - Air embolization has been shown to produce a reversible permeability-type of pulmonary oedema. The present study investigated the haemodynamic, gasometric and haematological changes associated with air infusion in the spontaneously breathing dog (weight 31 +/- 5 kg). Air was infused at a rate of 10 ml X min-1 for 60 min (10 dogs) or 180 min (5 dogs). During the air infusion, a dramatic increase in pulmonary artery pressure was associated with only a moderate increase in right atrial pressure and limited decreases in arterial pressure and in cardiac output. A marked decrease in end-tidal PCO2 reflected the increase in dead space. These changes were stable during air infusion, but rapidly reversed after the end of infusion. However, hypoxaemia, defined by a decreased PaO2/PAO2 ratio, deteriorated with time and was only partially reversible. At histological examination, interstitial pulmonary oedema was present around the pulmonary arterioles. Air infusion was associated with rapid decreases in circulating leukocytes and platelets and complement activation. Since leukotriene release might be associated with leukocyte activation in this model, seven additional dogs were pretreated by inhalation of 10 mg of the leukotriene inhibitor U 60,257. The increase in pulmonary vascular resistance and in pulmonary shunt were moderately reduced and the drop in circulating leukocytes and platelets was strikingly abolished in the treated animals. Air infusion in the spontaneously breathing dog represents a model of very stable and reversible pulmonary hypertension. It can reproduce important pathophysiological features implicated in the development of pulmonary oedema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094609 TI - Violence in the hospitalized adolescent: some considerations on the management of aggression in the long-term hospital unit. PMID- 3094610 TI - Hospital-based geriatric services in Great Britain: implications for the United States. PMID- 3094611 TI - Drug-resistant gonorrhea infections in Canada. Plasma-mediated resistance. PMID- 3094612 TI - Susceptibility of the Cebus apella monkey to different strains of T. cruzi after single or repeated inoculations. PMID- 3094613 TI - Breast-feeding and malnutrition in rural areas of northeast Brazil. PMID- 3094614 TI - A control chart method for evaluating hemagglutination reagent used in Chagas' disease diagnosis. PMID- 3094615 TI - AIDS: a problem for the transfusion service? AB - The first case of AIDS associated with blood transfusion was described in 1982. Over the following two years great advances were made in the understanding and prevention of this new hazard associated with blood transfusion, culminating in 1985 with the introduction of a screening test for blood donation. PMID- 3094616 TI - A comparative study of dose distribution of a high-energy electron beam and chromosome aberration frequencies. AB - Electron beam therapy is usually employed for the treatment of tumours located at or near the surface of the body, because the electron beam gives a high dose near the surface, but falls off rapidly with increasing depth beyond the level of the 80% depth dose. Isodose curves for radiotherapy have been obtained using physical methods, but have rarely been investigated on the basis of living human cells. In the present study, lymphocyte chromosome analysis was employed as a biological dosemeter for comparison with the isodose curve measured physically. The peripheral blood was exposed to a 14 MeV electron beam in a plastic tube set in a specially made test-tube stand immersed in a water tank. The chromosome aberration frequencies induced by irradiation of about 95% of peak dose at a depth of 31 mm were found to be higher in value than those induced at a depth of 17 mm where the peak dose had been determined physically. Three gray of irradiation given to whole blood in the presence of contrast medium gave rise to a slight enhancement of radiation-induced chromosome aberration frequencies in the lymphocytes exposed at a depth of 17 mm, but a slight decrease at 31 mm. PMID- 3094617 TI - Immunorestorative effect of lipid emulsions during total parenteral nutrition. AB - This prospective in vivo cross-over study investigated the effect of Intralipid on immune responses. Twenty-three patients were randomly allocated to receive one of two alternative total parenteral nutrition (TPN) regimens for the first 7 days and the other regimen for the second 7 days. Only one of the regimens included a fat emulsion to provide 50 per cent of the calorific requirement. Immunological studies were performed on days 0, 7 and 14. These included peripheral blood T cell subsets, antibody dependent cellular cytotoxicity and basal and maximal Interleukin 2 production. All immunological parameters were significantly augmented during total parenteral nutrition using the lipid based regimen. No such change was seen during intravenous feeding with carbohydrate based TPN. It is concluded that, far from being immunosuppressive, the incorporation of a fat emulsion into a TPN regimen has immunostimulatory properties. PMID- 3094618 TI - Successful autotransplantation of isolated islets of Langerhans in the cynomolgus monkey. AB - A recently described method for isolation of islets of Langerhans from the human pancreas has been adapted to the cynomolgus monkey pancreas. The mean yield of islets obtained from 13 monkey pancreata was 1319 islets per gram of pancreatic tissue (range 533-1800) and the usual purity of the preparation varied from 5 to 15 per cent islet tissue. Twelve cynomolgus monkeys underwent total pancreatectomy, preparation of islets from the excised pancreas and autotransplantation to either the spleen or the liver. Three animals received no transplant and became immediately diabetic, surviving 4-8 days. Four animals became normoglycaemic after intrasplenic islet transplantation, and survived 6 weeks, at which time splenectomy was performed with immediate onset of diabetes. Splenic vein insulin sampling confirmed the spleen as the source of insulin, and histological examination showed implanted islet tissue in all cases. Five animals became normoglycaemic after intrahepatic islet implantation. Three animals subsequently became diabetic at 4 and 5 months and two animals still have functioning grafts, the longest function being 9 months. These results suggest that in the cynomolgus monkey sufficient islets can be extracted from a single donor pancreas to reverse diabetes. PMID- 3094620 TI - Arthroscopic surgery of the knee. PMID- 3094619 TI - The pill and breast cancer: why the uncertainty? PMID- 3094621 TI - Prenatal diagnosis of the Turner syndrome: what to tell the parents. PMID- 3094622 TI - The flexible fibreoptic rhinolaryngoscope. PMID- 3094623 TI - The health of plantation workers. PMID- 3094624 TI - Platelet function defects in chronic alcoholism. AB - Platelet function in alcoholic patients was assessed on admission and during abstinence in hospital. On admission platelets from these patients were significantly less responsive (percentage aggregation and thromboxane A2 release) to conventional in vitro aggregating agents (adrenaline, adenosine diphosphate, and collagen) than platelets from healthy, moderate drinkers. Initially, platelet counts in platelet rich plasma tended to be low and the Simplate II bleeding times frequently prolonged. Platelet aggregation and thromboxane A2 release, however, were inhibited even in patients with normal platelet counts on admission. Platelet aggregation and thromboxane A2 release returned to normal or became hyper-responsive during two to three weeks of abstinence. Platelet counts rose during this period, the largest responses occurring in those patients with the lowest counts on admission. Bleeding times reverted to normal during abstinence and correlated significantly with changes in platelet aggregation, thromboxane A2 release, and platelet count and with the estimated ethanol consumption during the week before admission. Chronic, heavy alcohol ingestion evidently exerts an inhibitory effect on platelet function even in the absence of alcohol in the blood, and this phenomenon is reversible on abstaining. The impaired platelet function, together with the reduced platelet count, may contribute to the bleeding diathesis associated with chronic alcoholism and to the increased incidence and recurrence of gastrointestinal haemorrhage associated with excessive alcohol intake. PMID- 3094625 TI - Ultrasound screening for hip abnormalities: preliminary findings in 1001 neonates. AB - Several studies have documented the failure of neonatal clinical screening to reduce the incidence of hip dislocation later in infancy. In addition, the practice of splinting unstable hips is said to result in the treatment of many infants who would have developed normally if left unsplinted. Ultrasound provides a detailed image of the bony and cartilaginous neonatal hip. The results of conventional testing for hip instability were compared with ultrasound screening in 1001 neonates. As a result of the ultrasonic image 14 of 17 infants with hip instability were not splinted and developed normally. Two babies without detectable clinical signs were shown to have severe hip abnormalities. It is suggested that clinically normal but dysplastic hips do exist and that ultrasound will detect them. In addition, the overtreatment that is current practice might be avoided. PMID- 3094626 TI - Oral contraceptives and breast cancer: a national study. AB - In a population based case-control study 433 New Zealand women aged 25-54 with newly diagnosed breast cancer were compared with 897 women selected at random from the electoral rolls. The relative risk of breast cancer in women who had ever used oral contraceptives was 0.94 (95% confidence interval 0.70 to 1.25). The relative risk in women aged 25-34 at diagnosis was estimated to be 2.2 (95% confidence interval 0.47 to 9.9) and in older women less than 1. Analyses of risk by duration of use of oral contraceptives, age at first use, and time since first use showed no adverse effect of the pill. In particular, there was no increased risk in women who had used oral contraceptives before the age of 25 or before their first pregnancy, even for prolonged periods. Given the high prevalence of use in New Zealand, this study provides strong evidence against the hypothesis that use of oral contraceptives at young ages increases the risk of breast cancer. PMID- 3094627 TI - Does short term placebo treatment of chronic schizophrenia produce long term harm? AB - A randomised double blind placebo controlled trial is the most reliable method of assessing putative new developments in medical treatment. In schizophrenia, however, some clinicians believe that relapse contributes to long term deterioration and therefore that patients exposed to either placebo or an inactive new treatment may be put at a disadvantage in the long run if the trial leads to an additional relapse. A seven year follow up of patients included in a randomised placebo controlled trial of fluphenazine decanoate, in which 66% of the group given placebo relapsed compared with 8% of those who received the active drug, permitted examination of any long term adverse consequences in those patients who had received placebo. Seventy six (94%) of the 81 patients in the original trial were followed up. At the end of the follow up period there were no consistent or important differences in any measure of clinical or social outcome between the patients who had received placebo and those who had received the active drug. This negative finding has implications for the debate on the risk of placebo controlled trials of maintenance treatment in chronic schizophrenia. PMID- 3094628 TI - Plasminogen activators in human colorectal neoplasia. AB - A crucial step in the transition from adenomatous polyp to invasive colorectal cancer is the degradation of the epithelial basement membrane. Plasminogen activators may play a part in regulating the extracellular protease environment necessary for this to occur. Both functional and antigenic activity of the two principal activators of plasminogen, tissue plasminogen activator and urokinase, were measured in 30 colorectal cancers, matched samples of mucosa, and eight adenomatous polyps. Both polyps (p less than 0.01) and carcinomas (p less than 0.001) had raised urokinase activities compared with normal mucosa, the activity being highest in the carcinomas. Activity of tissue plasminogen activator, however, was diminished in both polyps (p less than 0.01) and carcinomas (p less than 0.001) compared with normal mucosa, the values being lowest in carcinomas. Plasmin generation by urokinase--in contrast with tissue plasminogen activator- is fibrin independent and thus less subject to physiological control. PMID- 3094629 TI - Clearance of psoriasis with low dose cyclosporin. PMID- 3094630 TI - Haemorrhagic cystitis due to gentian violet. PMID- 3094631 TI - Seasonal mortality among elderly people with unrestricted home heating. PMID- 3094632 TI - Response of secondary amyloidosis in psoriasis to treatment with etretinate and ultraviolet light. PMID- 3094633 TI - Pancreatitis induced by oestrogen in a patient with type I hyperlipoproteinaemia. PMID- 3094634 TI - Detection of patients with high alcohol intake by general practitioners. AB - General practitioners have the potential to treat patients with alcohol problems effectively. Despite the medical implications of excessive alcohol intake, it appears that general practitioners are not sufficiently aware of the drinking habits of their patients. The aim of the study was to investigate the accuracy of 56 randomly chosen general practitioners in detecting which of their patients had a high alcohol intake. Altogether, 2081 patients were recruited in general practitioners' waiting rooms, where they answered questions about their drinking habits. After the consultations general practitioners were asked to indicate the patients' levels of alcohol intake. The results showed that general practitioners correctly identified only 27.5% of patients who were classified as "high risk" drinkers, using Australian Medical Association criteria. They correctly identified only 45.2% of patients who were classified as "moderate to heavy" drinkers, defined by them as drinkers who consume four or more standard drinks a day. These findings have important implications for clinical practice since they indicate that general practitioners are failing to perform adequately in an important area of preventive medicine. This issue needs to be addressed in undergraduate and postgraduate medical education. PMID- 3094635 TI - Quality in general practice: case for the consumer. PMID- 3094636 TI - Physicians' attitudes to four common problems: hypertension, atrial fibrillation, transient ischaemic attacks, and angina pectoris. AB - A questionnaire was completed by 341 senior physicians on their attitudes to four common cardiovascular problems. Their replies showed that uncertainty about the end point for diastolic blood pressure still prevails and that their approach to the management of hypertension of differing severity in men and women of varying ages stems more from personal belief than from the results of clinical trials. Unless patients with atrial fibrillation also had mitral valve disease anticoagulation was not thought to be necessary, thereby making it ethically possible to carry out a trial of anticoagulants in stroke prevention on patients with atrial fibrillation but no valvular disease. The physicians' suggestions for very active management in transient ischaemic attacks extended beyond the evidence available to them, whereas their approach to the use of coronary arteriography closely reflected the results of clinical trials. These findings may indicate that recent cardiovascular trials that have provided definitive results have had more impact than earlier inadequate studies. PMID- 3094637 TI - Babies born in a district general hospital to mothers taking heroin. AB - The effect of maternal abuse of heroin on newborn babies was studied in 25 babies born during 1982-6 to 23 heroin users, most of whom smoked the drug. Nineteen of the babies developed withdrawal symptoms, which in 12 were severe enough to require treatment. Five babies were born prematurely; 17 were adequately grown for their gestational age. Four mothers successfully established breast feeding. Twenty two infants were discharged from the hospital into their mother's care with support from the family and community services; at the end of the study only six were living in families in which the parents were married or had a stable relationship. Withdrawal symptoms were short lasting and often self limiting, and no evidence of adverse effect on postnatal growth and development was found. Unstable social circumstances with changes in family dynamics made follow up difficult. Further assessment needs to be carried out to investigate the long term effect of maternal heroin abuse on children. PMID- 3094638 TI - Prolapse of a cervical disc in elderly patients with cervical spondylosis. PMID- 3094639 TI - Is skimping on care of the newborn false economy? PMID- 3094640 TI - Obstetric anaesthetic services. PMID- 3094641 TI - Why patients still die after paracetamol poisoning. PMID- 3094642 TI - Did the drug do it? PMID- 3094643 TI - Steroids in home treatment of children with acute asthma. PMID- 3094644 TI - Ingestion of button batteries. PMID- 3094645 TI - Whatever happened to the Black report? PMID- 3094646 TI - Dietary supplementation in pregnancy. PMID- 3094648 TI - Oral contraceptives and breast cancer. PMID- 3094647 TI - New estimates of radioactive discharges from Sellafield. PMID- 3094649 TI - Apoproteins: predictors of coronary heart disease? PMID- 3094650 TI - Half as many radiologists again by 1995. PMID- 3094651 TI - Urinary tract infection in the elderly. PMID- 3094652 TI - Campylobacter pyloridis: what role in gastritis and peptic ulcer. PMID- 3094653 TI - Drunken driving among the young. PMID- 3094654 TI - Finger systolic pressure: its use in screening for hypertension and monitoring. AB - A finger sphygmomanometer was compared with a mercury column sphygmomanometer for its ability to screen for hypertension. A total of 881 patients used each machine, both in initial screening and then for monitoring. The finger sphygmomanometer had a specificity of 98.5% in routine screening as compared with 97.6% for the mercury column device. Sensitivity of the finger device was 98.2%. These findings suggest that the finger sphygmomanometer using finger systolic pressure alone is adequate for screening and monitoring blood pressure. PMID- 3094655 TI - Demands on surgical inpatient services after mass mammographic screening. AB - The changes in the demand for surgical inpatient care created by mammographic screening for breast cancer were analysed by comparing two counties, one with and one without a mass screening campaign. A comprehensive computerised register of inpatient care in the region was used. The results indicate that population based screening offered to women above 40 years and repeated every two to three years will increase the number of operations required for breast cancer and inpatient days by at least 150% during the initial screening round. During the second round the figures tend to return to previous levels. Of decisive importance for the demands on health service resources are the specificity of screening, the duration of the first screening round, and the age groups included. PMID- 3094656 TI - Seroepidemiology of human immunodeficiency virus in Africa. AB - Serum samples from 6015 African subjects without symptoms of the acquired immune deficiency syndrome (AIDS) or contact with the disease were examined for antibodies to the human immunodeficiency virus by a combination of an enzyme linked immunosorbent assay and radioimmunoprecipitation (2567 samples) or by immunofluorescence (3448 samples). Serum samples had been collected between 1976 and 1984 in Senegal (n = 789), Liberia (935), Ivory Coast (1195), Burkina Faso (299), Nigeria (536), Gabon (1649), Zaire (15), Uganda (164), and Kenya (433). Only four samples contained antibodies. Three of these were from attenders at the Lambarene clinic in Gabon and one from a villager in Senegal. By contrast, two out of six AIDS suspects from Guinea-Bissau, all 13 patients with AIDS from Kinshasa (Zaire), and two out of three of their contacts were seropositive, all these specimens having been collected in 1985. These data show that fewer than one in a 1000 subjects were seropositive for AIDS at the time of sampling before 1985 and do not support the hypothesis of the disease originating in Africa. PMID- 3094658 TI - Effect of rapid referral on thickness of melanomas. PMID- 3094657 TI - Treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activator complex. AB - A controlled trial in 149 patients admitted to a district hospital with probable myocardial infarction tested the effect of 30 units of anisoylated plasminogen streptokinase activator complex (APSAC) on indices of infarct size. Patients were grouped prospectively according to whether they entered the trial within two and a half hours (early entry) or between two and a half and four hours (late entry) after onset of the symptoms. Sixty seven of 73 patients in the control group showed increased plasma activity of myocardial creatine kinase isoenzyme that was diagnostic of infarction compared with only 60 of 76 who received APSAC. The difference was significant overall but occurred predominantly in the early entry group. The patients who received APSAC had more early ventricular arrhythmias, compatible with reperfusion, and showed greater preservation of R waves during admission to hospital. Unwanted effects were generally minor and more common in the actively managed group than the control group (26% v 3%). After nine to 12 months of follow up 12 patients in the control group had died compared with seven in the actively managed group. The ease of administration and the apparent efficacy of APSAC suggest that it is suitable for use in a district hospital for patients with suspected acute myocardial infarction. PMID- 3094659 TI - The neuropathy of the critically ill. PMID- 3094660 TI - Effect of passive exposure to smoking on age at natural menopause. PMID- 3094661 TI - Practice newsletter: three years' experience. Practice Participation Association. PMID- 3094662 TI - Patterns of respiratory illness in the first year of life. AB - This paper describes a study of respiratory illness during the first year of life in a cohort of infants who were born between 1975 and 1978 to mothers who were registered with two inner London group general practices. The types of respiratory illness and their relation to the season of the year and season of birth of the child are examined. The relations among the frequency and type of respiratory illness and several social and family factors that have previously been shown to be associated with high levels of respiratory morbidity are also described. PMID- 3094663 TI - Clinical and bronchoscopic diagnosis of suspected pneumonia related to AIDS. AB - In a series of 25 patients with suspected pneumonia related to the acquired immune deficiency syndrome (AIDS) the first 12 underwent routine fibreoptic bronchoscopy and bronchoalveolar lavage with or without transbronchial biopsy before treatment. Eight were found to have Pneumocystis carinii pneumonia and had typical clinical presentations with a prolonged history of symptoms, including a dry cough, and bilateral diffuse alveolar or interstitial shadowing in chest radiographs. Among the subsequent 13 cases, 11 had similar clinical presentations and were treated with high doses of intravenous co-trimoxazole without bronchoscopy first. Bronchoscopy was performed in those who deteriorated at any stage or failed to improve by the fifth day of treatment. Nine patients recovered and were discharged. In two patients who died P carinii pneumonia was confirmed in one but no diagnosis was made in the other. The early and late survival in both groups of patients was similar. In patients at high risk for AIDS who have clinical features suggestive of P carinii pneumonia starting treatment with intravenous co-trimoxazole is justified. The few patients who deteriorate or fail to respond should undergo bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. PMID- 3094665 TI - Rest pain and leg ulceration due to syphilitic osteomyelitis of the tibia. PMID- 3094664 TI - Computer aided diagnosis of acute abdominal pain: a multicentre study. AB - A multicentre study of computer aided diagnosis for patients with acute abdominal pain was performed in eight centres with over 250 participating doctors and 16,737 patients. Performance in diagnosis and decision making was compared over two periods: a test period (when a small computer system was provided to aid diagnosis) and a baseline period (before the system was installed). The two periods were well matched for type of case and rate of accrual. The system proved reliable and was used in 75.1% of possible cases. User reaction was broadly favourable. During the test period improvements were noted in diagnosis, decision making, and patient outcome. Initial diagnostic accuracy rose from 45.6% to 65.3%. The negative laparotomy rate fell by almost half, as did the perforation rate among patients with appendicitis (from 23.7% to 11.5%). The bad management error rate fell from 0.9% to 0.2%, and the observed mortality fell by 22.0%. The savings made were estimated as amounting to 278 laparotomies and 8,516 bed nights during the trial period--equivalent throughout the National Health Service to annual savings in resources worth over 20m pounds and direct cost savings of over 5m pounds. Computer aided diagnosis is a useful system for improving diagnosis and encouraging better clinical practice. PMID- 3094666 TI - A primary health care project in the Amazonian jungle of northern Peru. PMID- 3094668 TI - Management of infection in the neutropenic patient. PMID- 3094667 TI - Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine replacement? AB - To establish their role in monitoring patients receiving thyroxine replacement biochemical tests of thyroid function were performed in 148 hypothyroid patients studied prospectively. Measurements of serum concentrations of total thyroxine, analogue free thyroxine, total triiodothyronine, analogue free triiodothyronine, and thyroid stimulating hormone, made with a sensitive immunoradiometric assay, did not, except in patients with gross abnormalities, distinguish euthyroid patients from those who were receiving inadequate or excessive replacement. These measurements are therefore of little, if any, value in monitoring patients receiving thyroxine replacement. To stop doing thyroid function tests in these cases would result in considerable savings nationally in the cost of reagents in laboratories using commercial kits. PMID- 3094669 TI - Identifying men at high risk of heart attacks. PMID- 3094670 TI - Spontaneous pneumomediastinum in two stowaways. PMID- 3094671 TI - Morphine intoxication in renal failure: the role of morphine-6-glucuronide. PMID- 3094673 TI - Disclosure of diagnosis of acquired immune deficiency syndrome. PMID- 3094672 TI - Markers of HTLV-III in patients with end stage renal failure treated by haemodialysis. PMID- 3094674 TI - Angina pectoris-like pain provoked by intravenous infusion of adenosine. PMID- 3094675 TI - Low concentrations of formaldehyde in bronchial asthma. PMID- 3094676 TI - Risk factors for uterine fibroids. PMID- 3094677 TI - Role of general practitioners in treating opiate misuse. PMID- 3094678 TI - Death after bereavement. PMID- 3094679 TI - Normal pressure hydrocephalus. PMID- 3094680 TI - Splenic irradiation in treating warm autoimmune haemolytic anaemia. AB - An elderly man with severe congestive heart failure was noted to have a haemoglobin concentration of 87 g/l and a reticulocyte count of 13%. Direct Coombs test yielded a positive result and the serum contained a moderate amount of warm antibody (IgG class). Steroids were given, but to no avail, and the patient's condition precluded splenectomy. A course of splenic irradiation was therefore tried (midline dose 2000 cGy (rads)), and 60 days later the blood film showed similar appearances to those in patients treated successfully by splenectomy. Haemoglobin concentration subsequently rose to normal. Splenic irradiation may offer a simple treatment for resistant warm autoimmune haemolytic anaemia when splenectomy is contraindicated. PMID- 3094681 TI - Metabolic abnormalities in children of non-insulin dependent diabetics. AB - Non-insulin dependent diabetes appears to be an inherited condition. A study of young offspring of non-insulin dependent diabetics was conducted to determine whether metabolic abnormalities could be found at a young age before clinical diabetes developed. Thirteen patients with non-insulin dependent diabetes were selected who fulfilled the following criteria: they had a sibling who also had non-insulin dependent diabetes, their spouse was non-diabetic, and the offspring were aged between 12 and 45 years, not diabetic, and available for study. All 32 offspring had a 75 g oral glucose tolerance test, and results in 13 of them, one randomly selected from each family, were compared with 13 controls of similar age, sex, and weight. The offspring had significantly higher fasting concentrations of glucose, higher proportions of haemoglobin A1, and higher concentrations of insulin, C peptide, and glucagon. After glucose challenge the increases in both glucose and C peptide concentrations were significantly greater in the offspring. These differences were maintained in all 32 offspring when compared with 18 controls of similar age, sex, and weight; seven of the 32 offspring had impaired glucose tolerance. These results indicate that young offspring of selected non-insulin dependent diabetics can show extensive metabolic changes including impaired glucose tolerance. These changes are associated with hyperinsulinaemia and hyperglucagonaemia. PMID- 3094682 TI - Asthma and climatic conditions: experience from Bermuda, an isolated island community. AB - A retrospective study of patients attending the emergency department with acute asthma was performed in Bermuda. Climatic data (barometric pressure, rainfall, humidity, and wind strength and direction) were obtained and compared with frequency of exacerbations of asthma. Three factors--namely, relative humidity, average daily temperature, and northeasterly winds--were found to be related to worsening asthma. Owing to Bermuda's lack of pollution and aeroallergens it was thought that these weather parameters had a direct effect on the asthmatic population. PMID- 3094683 TI - Mortality of workers at the Sellafield plant of British Nuclear Fuels. AB - The mortality of all 14,327 people who were known to have been employed at the Sellafield plant of British Nuclear Fuels at any time between the opening of the site in 1947 and 31 December 1975 was studied up to the end of 1983. The vital state of 96% of the workers was traced satisfactorily and 2277 were found to have died, 572 (25%) from cancer. On average the workers suffered a mortality from all causes that was 2% less than that of the general population of England and Wales and 9% less than that of the population of Cumberland (the area in which the plant is sited). Their mortality from cancers of all kinds was 5% less than that of England and Wales and 3% less than that of Cumberland. In the five years after their first employment Sellafield workers had an overall mortality that was 70% of that of England and Wales, probably due to healthier members of the population being selected for employment. Raised death rates from cancers of several specific sites were found, but only for those of ill defined and secondary sites was the excess statistically significant (30 observed, 19.7 expected). For cancers of the liver and gall bladder there was a significant deficit of deaths (four observed, 10.5 expected). Workers in areas of the plant where radiation exposure was likely were issued with dosimeters to measure their external exposure to ionising radiations. Personal dose records were maintained for workers who entered such areas other than infrequently. Workers with personal dose records ("radiation" workers) had lower death rates from all causes combined than other workers but the death rates from cancer in the two groups were similar. Compared with the general population radiation workers had statistically significant deficits of liver and gall bladder cancer, lung cancer, and Hodgkin's disease. There were excesses of deaths from myeloma (seven observed, 4.2 expected) and prostatic cancer (19 observed, 15.8 expected) but these were not significant and there was no evidence of an excess of leukaemia (10 deaths observed, 12.2 expected) or cancer of the pancreas (15 observed, 17.8 expected). Non-radiation workers had a significant deficit of leukaemia (one death observed, 5.1 expected) and a significant excess of cancers of ill defined and secondary sites (13 deaths observed, 5.8 expected). For no type of cancer was the ratio of observed to expected deaths significantly different between radiation and non radiation workers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3094684 TI - Right superior vena cava draining into the left atrium with left superior vena cava draining into the right atrium. PMID- 3094685 TI - Munchausen's syndrome by proxy: a warning for health professionals. PMID- 3094686 TI - Blowing hot and cold: "near miss" sudden infant death and episodic hypothermia. PMID- 3094687 TI - Effect on prescribing of the limited list in a computerised group practice. AB - The prescribing of drugs in the therapeutic classes that are affected by the government's limited list was investigated in a computerised group practice of just over 3,000 patients. Prescribable drugs in categories that are affected by the list were identified for two consecutive six month periods before and one six month period after the introduction of the list. A significant decrease in the prescribing of cough and cold remedies, vitamins, and antacids occurred after the list was introduced, whereas no change occurred in the prescribing of laxatives, benzodiazepines, or analgesics. The prescribing of iron and penicillin increased significantly after the list was introduced, whereas the use of H2 antagonists and non-steroidal anti-inflammatory drugs showed no significant change. PMID- 3094688 TI - Injuries of the spine sustained during gymnastic activities. AB - Between 1954 and 1984, 38 patients were seen as a result of gymnastic activities. Thirty three were men, five were women, and their ages ranged from 12 to 54, the mean age being 20. Thirty one had spinal injuries (28 in the cervical region, three in the thoracolumbar region), two no definite injury, and for five the information was incomplete. The accidents occurred largely because gymnasts landed on their heads, the force being transmitted to the cervical spine. Most took place in gymnasiums and were caused by a failure of supervision. PMID- 3094689 TI - Sir Harry Platt: 100 not out. PMID- 3094690 TI - Private nursing homes: contribution to long stay care of the elderly in the Brighton Health District. AB - Two surveys of private nursing homes, designated geriatric wards, and a sample of social service part III homes were carried out in the Brighton Health District using questionnaires supplemented (in the second survey) by some interviews. The dependency of old people in the private nursing homes was more like that of long stay hospital patients rather than that of residents in social services homes. In the private nursing homes, however, a smaller proportion of patients were in the medium to heavy nursing category (178 (31%) compared with 158 (63%) in the hospital long stay wards) and a larger proportion in the heavy nursing category (170 (30%) compared with 44 (17%) in the long stay wards). Of the patients in private nursing homes, 401 (82%) were local residents, 488 (86%) were long stay, and 459 (88%) were women; their mean age was 88 years. Two thirds of the patients were over 80. There were no significant differences between the private nursing homes and the wards in nursing workloads or staffing, except for a slightly higher provision of state registered nurses in the private sector. In the private nursing homes 348 (63%) of the patients had fees paid by private funds, 26 (5%) were in contract beds paid for by the National Health Service, and 176 (32%) were subsidized by the Department of Health and Social Security. Private nursing homes make a substantial contribution to the care of the elderly in the Brighton Health District, and the health authority should develop a more active partnership with this sector. PMID- 3094692 TI - Immunity and depression. PMID- 3094693 TI - AIDS: act now, don't pay later. PMID- 3094691 TI - Cytotoxic chemotherapy for common adult malignancies: "the emperor's new clothes" revisited? PMID- 3094694 TI - Psoriasis. PMID- 3094696 TI - Programme for early detection of gastric cancer. PMID- 3094695 TI - Epidemics of fractures during periods of snow or ice. PMID- 3094697 TI - A case of scurvy. PMID- 3094698 TI - A complication of capillary glucose monitoring. PMID- 3094699 TI - The perfect rabies vaccine. PMID- 3094700 TI - Continuous ambulatory peritoneal dialysis fluid: another fluid positive for HIV antibody. PMID- 3094701 TI - Incidence of rhesus immunisation after genetic amniocentesis. PMID- 3094702 TI - New method for typing Staphylococcus aureus resistant to methicillin. PMID- 3094703 TI - Obstetric anesthetic services. PMID- 3094704 TI - Recommendations on blood pressure measurement. PMID- 3094705 TI - Use of captopril in insulin dependent diabetics. PMID- 3094706 TI - Survey of recently appointed consultants in geriatric medicine. PMID- 3094707 TI - Glimpses of the mechanisms of hypertension. PMID- 3094708 TI - Pacemaker syndrome. PMID- 3094709 TI - Weight gain in pregnancy: eating for two or just getting fat? PMID- 3094710 TI - Doctors and the drug industry: too close for comfort. PMID- 3094711 TI - Effect of aspirin on pruritus. AB - The effect of 900 mg aspirin on persistent itch from chronic dermatoses other than urticaria (eight patients) and other causes (five patients) was measured subjectively using a 10 cm line and objectively as nocturnal scratch using limb meters. There was no change in itch or scratch and it is concluded that aspirin neither affects itch centrally by a pain related mechanism nor affects itch physiologically by cyclo-oxygenase inhibition in the skin. PMID- 3094712 TI - Humoral response to wheat protein in patients with coeliac disease and enteropathy associated T cell lymphoma. AB - Features that might distinguish uncomplicated coeliac disease from enteropathy associated T cell lymphoma were investigated. Of 76 patients with coeliac disease, 71 (93%) had raised levels of alpha gliadin antibody and all responded clinically and histologically to treatment with a gluten free diet. In contrast, none of 16 patients with enteropathy associated T cell lymphoma had raised levels of alpha gliadin antibody, and treatment with a gluten free diet resulted in histological improvement in one and transient clinical improvement in six patients. The ratio of women to men was 2.2:1 in the group with coeliac disease and 1:1.6 in the patients with enteropathy associated T cell lymphoma. Thus patients with enteropathy associated T cell lymphoma do not display a humoral immune response to wheat protein (alpha gliadin), rarely respond to a gluten free diet, and are often men. Patients with uncomplicated coeliac disease usually have raised levels of alpha gliadin antibody, always respond to a gluten free diet, and are frequently women. These findings suggest the presence of two separate forms of enteropathy: one is benign and sensitive to wheat protein whereas the other runs a malignant course. PMID- 3094713 TI - Contribution of inappropriate treatment for hypertension to pathogenesis of stroke in the elderly. AB - One hundred and seventy eight patients admitted to hospital with acute cerebral infarction or transient ischaemic attack were studied to determine if their treatment had been changed during the previous three weeks and to compare their blood pressure after the stroke with premorbid values. Blood pressure measurements taken within one year before the stroke were available for 100 patients; seven of these had had a recent change in antihypertensive or diuretic treatment. Of these, three patients who had started taking frusemide because of hypertension and one whose dosage of a reserpine combination drug had been increased experienced an appreciable decrease in blood pressure immediately after the stroke; they also showed signs of haemoconcentration. The change in treatment probably contributed to the stroke in these four patients. The other three showed a smaller decrease or even an increase in blood pressure and no signs of haemoconcentration; the relation between the change in treatment and stroke is less likely in these patients. The use of high ceiling diuretics such as frusemide in the treatment of hypertension may induce hypovolaemia and hypotension, resulting in cerebral ischaemia, and are therefore best avoided in such treatment. PMID- 3094714 TI - Determinants and importance of stress hyperglycaemia in non-diabetic patients with myocardial infarction. AB - Determinants of plasma glucose concentrations were studied in patients on admission to hospital with confirmed acute myocardial infarction but without previous glucose intolerance as evidenced by raised concentrations of glycosylated haemoglobin (HbAlc). Mortality in hospital increased significantly with increasing plasma concentrations of glucose in patients with both normal (p less than 0.0001, n = 311) and borderline (p less than 0.02, n = 70) concentrations of HbAlc. There was a weak relation between plasma glucose concentrations and infarct size as estimated by peak aspartate transaminase activity in both HbAlc groups (rs = 0.26, n = 101 and rs = 0.41, n = 35 respectively). A correlation was found between adrenaline and plasma glucose concentrations (r = 0.47, n = 27) and cortisol and plasma glucose concentrations (r = 0.75, n = 19), but the relation of plasma noradrenaline and plasma glucose suggested a threshold effect. Concentrations of adrenaline, but not those of noradrenaline or cortisol, correlated with infarct size as measured both by peak aspartate transaminase activity and cumulative release of creatine kinase MB isoenzyme. Multiple regression analysis showed that concentrations of cortisol, adrenaline, and noradrenaline (but not the concentration of HbAlc, infarct size, or age) are the main determinants of plasma glucose concentration measured in non diabetic patients when admitted to hospital after acute myocardial infarction. PMID- 3094715 TI - Thrombotic microangiopathy and acute renal failure associated with arteriography. PMID- 3094716 TI - Availability of organs for transplantation: a three year study. PMID- 3094717 TI - Nifedipine in the treatment of chilblains. PMID- 3094718 TI - Willingness of homosexual and bisexual men in London to be screened for human immunodeficiency virus. PMID- 3094719 TI - Outcome of respiratory illness occurring in the first year of life. AB - This paper describes the outcome of respiratory illness presented by a birth cohort of infants in the first year of life who were born to mothers in two inner London group general practices in terms of the ventilatory capacity measured at their fifth birthday. A history of two or more episodes of "lower" respiratory illness in the first year of life was associated with a significant reduction in peak expiratory flow when compared with those who had no such history. Boys had significantly higher peak flow rates than girls; those whose parents were in manual occupations had significantly lower peak flow rates than those whose parents were in non-manual occupations. There was a significant interaction between sex and social class. PMID- 3094720 TI - Unemployment and illegal drug use: concordant evidence from a prospective study and national trends. AB - Data from a previous study of 1036 young people in the Lothian region that indicated an association between unemployment and illegal drug use were examined in more depth to investigate the inter-relation between duration of unemployment and the use of illegal drugs, alcohol, and tobacco. After factors such as social class background and educational qualifications had been taken into account a weak but significant association was found between duration of unemployment and illegal drug use. No such association was found for alcohol or tobacco. Similar results were obtained from an analysis of national statistics related to unemployment and illegal drug use. Both sets of data thus indicate that illegal drug use is moderately associated with unemployment. PMID- 3094721 TI - Malaria prophylaxis: survey of the response of British travellers to prophylactic advice. AB - A cohort study was conducted to determine the compliance of travellers with chemoprophylactic advice given over the telephone by the malaria reference advisory service. Travellers who visited their general practitioner first for advice about malaria prophylaxis were often advised to consult a specialist service themselves. Compliance fell in travellers who were given complicated information and those who received conflicting advice when they contacted other advisory services. After returning to Britain 48% of the travellers reported that they were fully compliant with prophylactic advice; over a third of the travellers studied did not maintain prophylaxis on their return. PMID- 3094722 TI - Effect of continuous ambulatory peritoneal dialysis on a British renal unit. AB - Experience in the use of continuous ambulatory peritoneal dialysis (CAPD) for the treatment of end stage renal failure in Nottingham was reviewed. During six years 150 patients aged from 11 to 73 received this type of treatment. At three years patient actuarial survival was 69% and CAPD technique survival was 41%. Although CAPD was satisfactory as a first treatment for many patients, its long term use was possible in only a few. Actuarial survival of patients who changed to haemodialysis was 64% at one year after the change, suggesting that unsuccessful CAPD increased the risk of death. Hospital haemodialysis was the only suitable form of treatment for most patients in whom CAPD had been abandoned. British renal units have adopted CAPD to a much greater extent than those in Europe, but care in the selection of patients is necessary to reduce mortality, and many patients may eventually need hospital haemodialysis. Greater numbers of hospital haemodialysis places will probably have to be made available to meet this extra demand. PMID- 3094723 TI - Continuous ambulatory peritoneal dialysis after the honeymoon: review of experience in Newcastle 1979-84. AB - Two hundred and twenty nine consecutive patients (129 men, mean age 45) were reviewed 12 to 65 months after starting treatment with continuous ambulatory peritoneal dialysis (CAPD) from January 1979 to December 1983. They received CAPD for a mean of 19.8 (range 0.5-62) months. Actuarial patient survival was 79% at 24 months and 72% at 36 months. Half of the 46 deaths were related to cardiovascular disease, while eight patients died of abdominal complications, including three patients with peritonitis. Peritonitis occurred at a rate of one episode per 35 patient weeks, and 88% of episodes were cleared by one or more courses of antibiotics. This still left peritonitis as the commonest cause of failure of CAPD, leading to a permanent change of treatment in 44 patients and temporary interruption in a further 25. CAPD remains a reasonable medium term treatment in chronic renal failure. Despite the persisting problem of peritonitis the results are comparable with those achieved by haemodialysis, and CAPD has become the treatment of first choice for end stage renal failure in Newcastle. In younger patients judged unsuitable for transplantation and facing long term dialysis, however, haemodialysis is preferred. PMID- 3094724 TI - Sexually transmitted disease surveillance in Britain--1984. Communicable Disease Surveillance Centre. PMID- 3094725 TI - "One man's vodka is another man's firewater": international comparisons of drinking and drinking problems. PMID- 3094726 TI - Consensus development conference: treatment of primary breast cancer. PMID- 3094727 TI - Childhood leukemia and radioactive discharges at Seascale. PMID- 3094728 TI - Orchidectomy versus oestrogen for prostatic cancer: cardiovascular effects. PMID- 3094729 TI - Obstetric ultrasound: getting good vibrations. PMID- 3094730 TI - Treatment of functional abdominal pain by transcutaneous nerve stimulation. PMID- 3094731 TI - Hazards of bronchoscopy. PMID- 3094732 TI - Antiviral treatment in chronic infection with hepatitis B virus. PMID- 3094733 TI - Increased risk of sudden infant death syndrome in older infants at weekends. PMID- 3094734 TI - Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. PMID- 3094735 TI - Drug induced parkinsonism. PMID- 3094736 TI - Guidelines for selective radiological assessment of inversion ankle injuries. PMID- 3094737 TI - Incarcerated inguinal hernia in infants. PMID- 3094738 TI - Sources and patterns of referral of oral cancer. PMID- 3094739 TI - Why not add methionine to paracetamol tablets? PMID- 3094740 TI - Manpower. PMID- 3094741 TI - Differences between neurological and neurosurgical approaches in the management of malignant brain tumours. AB - The management and outcome in 205 patients diagnosed as having cerebral gliomas over five years were reviewed. Patients referred to neurologists and neurosurgeons had similar clinical features and similar results on computed tomography. Patients referred to neurologists underwent burr hole biopsy less often and had better short term morbidity than patients referred to neurosurgeons, although final outcome was the same in both groups. Few patients underwent other surgical procedures. Referral for radiotherapy was usually by neurosurgeons, although this did not significantly affect long term survival. The implications for the management of patients with primary malignant brain tumours and the need for prospective studies are discussed. PMID- 3094742 TI - Halothane and the liver. PMID- 3094743 TI - Is there an ideal body weight. PMID- 3094744 TI - Glue ear and speech development. PMID- 3094745 TI - Use of molar units for drugs and toxins. PMID- 3094746 TI - Computer aided diagnosis of acute abdominal pain. PMID- 3094747 TI - Referral to medical outpatients department at teaching hospitals in Birmingham and Amsterdam. PMID- 3094748 TI - Ultrasound screening for hip abnormalities. PMID- 3094749 TI - Risk factors for uterine fibroids: reduced risk associated with oral contraceptives. PMID- 3094750 TI - Angina pectoris-like pains provoked by intravenous adenosine. PMID- 3094752 TI - Obstetric anaesthetic services. PMID- 3094751 TI - Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy. PMID- 3094753 TI - The truth about government spending on the NHS. PMID- 3094754 TI - DHSS waiting list statistics--a major deception? PMID- 3094755 TI - Alcohol: a new report, but still going backwards. PMID- 3094756 TI - Treating ovarian cancer. PMID- 3094757 TI - Indium-111 leucocyte scanning--underused? PMID- 3094758 TI - Where should low birthweight babies be born? PMID- 3094759 TI - Trace element analysis of hair. PMID- 3094760 TI - Consumer representation in the NHS. PMID- 3094761 TI - Visceral and skin granuloma annulare, diabetes, and polyendocrine disease. AB - A middle aged man suffered with insulin dependent diabetes, autoimmune Addison's disease, myxoedema, and severe ulcerative colitis, for which he had undergone subtotal colectomy with formation of an ileostomy. Granuloma annulare confined to the anterior abdominal wall was diagnosed in 1981. In 1983 an episode of severe colicky pain and excessive working of the ileostomy occurred associated with severe hyperglycaemia and increased irritation of the granuloma annulare. Laparotomy disclosed adhesions and numerous white nodules over bowel, mesentery, and peritoneum histologically identical with the skin lesions. Two further episodes of subacute small bowel obstruction occurred, and a repeat laparotomy showed widespread intra-abdominal granuloma annulare. Visceral granuloma annulare appears not to have been reported before, and in this patient exacerbation of the skin lesion was associated with poor diabetic control. PMID- 3094762 TI - Impaired cell mediated immunity in haemophilia in the absence of infection with human immunodeficiency virus. AB - The cell mediated immune response was evaluated in vivo in 29 patients with clinically severe haemophilia by means of the dinitrochlorobenzene skin test. All patients had a response below the median normal value, and in 19 the response was on or below the lower limit of the normal range. There was no difference in skin response between patients positive and negative for the human immunodeficiency virus (HIV; formerly known as human T cell lymphotropic virus III or lymphadenopathy associated virus). In the whole group, and in seronegative patients (n = 17), there was an inverse relation between exposure to clotting factor and skin response. In seropositive patients (n = 12) no such association was apparent. This study shows that clotting factor concentrate impairs the cell mediated immune response to a new antigen in the absence of infection with HIV. PMID- 3094763 TI - Effect of birthplace on infants with low birth weight. AB - From December 1983 to June 1985, 162 infants of less than 32 weeks' gestation or weighing less than 1,500 g, or both, were cared for at the regional neonatal intensive care unit in Leeds. Of the 162, 64 (40%) were born in the unit because their mothers had received antenatal care there, 58 (36%) were born in another hospital and subsequently transferred, and 40 (25%) were transferred in utero because of potential complications. The overall mortalities for each group were 14%, 38%, and 18% respectively. These differences were significant, but when they were corrected for gestation, birth weight, and mode of delivery there was no difference in either the mortality or the incidence of intraventricular haemorrhage in the three study populations. Although there seem to be no distinct advantages of in utero transfer in terms of mortality and morbidity, there are other psychological and emotional advantages. PMID- 3094764 TI - Effects of nutrient intake, surgery, sepsis, and long term administration of steroids on muscle function. AB - The stimulated contraction-relaxation characteristics of the adductor pollicis muscle were used to assess nutritional state in patients and healthy controls. In both groups insufficient nutrition resulted in abnormal muscle function. The ratio of force of contraction at 10 Hz to that at 20 Hz yielded the best combination of sensitivity (87%) and specificity (82%). Sepsis resulted in abnormal muscle function, but the changes were easily distinguishable from those in subjects taking an inadequate diet. Long term administration of steroids, trauma, and surgery had no effect on muscle function. A prospective study of 11 malnourished patients with abnormal muscle function showed that all variables of muscle function returned to normal values with total parenteral nutrition. This reversal correlated significantly with the duration of parenteral nutrition and occurred before any change in anthropometric variables or plasma albumin concentration. Muscle function studies are sensitive and specific indicators of malnutrition; results depend on energy intake but are not influenced by administration of steroids, trauma, or surgery. PMID- 3094765 TI - Zinc state in anorexia nervosa. PMID- 3094766 TI - Subacute encephalopathy associated with human immunodeficiency virus in haemophilia A. PMID- 3094767 TI - Hypothyroidism after treatment with ketoconazole. PMID- 3094768 TI - Omeprazole as adjunct to enzyme replacement in severe pancreatic insufficiency. PMID- 3094769 TI - Measles immunisation rates and the good practice allowance. AB - The recent discussion document on primary health care proposes that a good practice allowance is paid to general practitioners based in part on the uptake of immunisation by patients. The variation between and the validity of practice immunisation rates for measles as determined by one district health authority's child health computer are assessed. In areas of low population mobility district health authority rates may be sufficiently accurate to base a good practice allowance on but should not be used until the social environment of each practice can also be characterised. In areas of high mobility intermittent surveys may be a preferable method of auditing performance. PMID- 3094770 TI - Schoolgirl mothers. PMID- 3094771 TI - Hormonal changes in non-endocrine disease. PMID- 3094773 TI - Muscle power after glucose-potassium loading in undernourished patients. AB - The force-frequency characteristics and maximal relaxation rate of the adductor pollicis muscle were measured before and after 48 hours of intravenous loading with glucose (104.5 kJ (25 kcal)/kg/24 h) and potassium (20 mmol(mEq)/500 ml glucose) in eight undernourished patients about to undergo surgery. Both variables of skeletal muscle performance, which were depressed when compared with data from 100 healthy volunteers, improved significantly after glucose-potassium loading. The improvement was accompanied by restoration of muscle glycogen values and return of respiratory exchange ratios towards unity. These results imply that if muscle power is a yardstick for preoperative nutritional rehabilitation then a simple regimen of energy-electrolyte repletion may be cost effective in preparing undernourished patients for major surgery. PMID- 3094772 TI - Sural nerve oxygen tension in diabetes. AB - Peripheral nerve oxygen tensions were assessed in vivo by using microelectrodes to measure endoneurial oxygen tension in exposed sural nerve. In 11 diabetic patients with chronic sensorimotor neuropathy the mean endoneurial oxygen tension was 39.7 (SD 10.2) mm Hg. In all but one patient compared with none of four non neuropathic subjects the mean nerve oxygen tensions were below dorsal foot vein values. This unphysiological state may have a role in the aetiology of diabetic neuropathy. PMID- 3094774 TI - Blood cyclosporin concentrations and renal allograft dysfunction. AB - Forty nine renal allograft recipients taking oral cyclosporin suffered 76 episodes of renal dysfunction within six months of transplantation. These episodes were diagnosed as graft rejection or cyclosporin induced nephrotoxicity on the basis of histological findings in allograft biopsy specimens and the response to treatment. Mean predose blood cyclosporin concentrations measured by radioimmunoassay during the week before the onset of renal dysfunction were significantly higher when the cause was cyclosporin toxicity rather than graft rejection (392 v 741 nmol/l (471 v 891 ng/ml). During this period there was a significant association between both the frequency of measurements above 666 nmol/l (800 ng/ml) and the diagnosis of toxicity and the frequency of measurements below 333 nmol/l (400 ng/ml) and the diagnosis of allograft rejection. Cyclosporin measurements made at the time of biopsy and reference to the highest or lowest concentrations measured during the week preceding biopsy were of less value in distinguishing between the two groups. Despite lacking specificity for the parent compound, the radioimmunoassay used produced results which were of clinical value in optimising cyclosporin treatment. PMID- 3094775 TI - Prolonged pregnancy: the management debate. AB - A prospective trial was conducted to compare the effects of conservative management of prolonged pregnancy (conservative group) with routine induction of labour at 42 weeks' gestation (active group) in otherwise uncomplicated pregnancies. Of the 402 pregnancies studied, 207 (51%) were allocated to conservative management and 195 (49%) were allocated to have labour induced. The groups were well matched for age, parity, and smoking habits. One hundred and sixty six (80%) of the patients in the conservative group went into spontaneous labour. Of the remainder, two underwent elective caesarean section, 19 had labour induced because of clinical concern, and the remaining 20 had labour induced at the patient's own request. One hundred and twenty five (64%) of the patients in the planned active group underwent induction of labour. Of the remaining 70, 49 went into spontaneous labour and 21 (11%) asked that they should not have labour induced. Comparison of the two groups showed no difference in the length of the first stage of labour but a trend towards an increased need for intervention for fetal distress (p less than 0.06) in the active group. There were no differences in the length of the second stage, the need for intervention, or the mode of delivery. In terms of Apgar scores the neonatal outcome was not significantly different between the two groups, but a greater proportion of the babies (15% v 8%) in the active group required intubation. Umbilical cord venous pH estimated in the last 183 consecutive deliveries in the study showed a significantly lower mean value in the active group (p less than 0.05). There was no difference in birth weight between the two groups. Two deaths occurred in the study. There was a stillbirth in the conservative group at 292 days after massive abruption, and one neonatal death in the active group owing to multiple congenital abnormalities. The outcome for mother and baby in patients from both groups who went into spontaneous labour was generally good. The outcome for patients for whom conservative management was planned but induction became necessary was no different from that of patients who underwent planned induction at term. Thus from our results we can find no evidence to support the view that women with normal prolonged pregnancy should undergo routine induction of labour at 42 weeks' gestation. PMID- 3094776 TI - Randomised comparison of procedures for obtaining informed consent in clinical trials of treatment for cancer. AB - Methods of obtaining informed consent have evolved differently in Western countries without substantive information on the impact of these different practices on the patients. A randomised study was performed to compare two commonly adopted methods of seeking consent to randomised treatment: an individual approach at the discretion of each doctor and a uniform policy of total disclosure of all relevant information. The impact of both consent procedures on the patient's understanding and anxiety levels and on the doctor patient relationship was assessed by means of a questionnaire given soon after the consent interview. Fifty seven patients were assigned at random to two groups: to 29 patients an individual approach to seeking consent was adopted and to 28 patients all relevant information was given. Seven patients refused consent to randomised treatment, with slightly more refusals by patients in the total disclosure group (5 v 2, p = 0.25). The main effects of total disclosure of all information compared with an individual approach to seeking consent were: a better understanding of treatment and side effects and of research aspects of the treatments; less willingness to agree to randomised treatment; and increased anxiety. No significant differences were found in patients' perceptions of the doctor-patient relationship. A repeat questionnaire given three to four weeks later no longer showed significant differences between the two groups. PMID- 3094777 TI - Decline in cardiovascular mortality in North Karelia and other parts of Finland. AB - The trends in mortality from ischaemic heart disease, cerebrovascular stroke, and all cardiovascular diseases were analysed for the province of North Karelia and for the rest of Finland. Linear trends in mortality were computed for the population aged 35 to 64 for the period from 1969 to 1982, and changes in mortality between the three year means of 1969-71 and 1980-2 were calculated. In North Karelia, where a community based preventive programme has been carried out since 1972, the annual decline in mortality from ischaemic heart disease in men was on average 2.9%, whereas in the rest of Finland it was 2.0%. For women the respective average annual declines in mortality were 4.9% and 3.0%. The net decline from 1969-71 to 1980-2 in North Karelia was 100 deaths/100,000 men. The annual mortality from all cardiovascular disease in men decreased by 2.9% in North Karelia and by 2.6% in the rest of Finland; in women the decreases were 6.0% and 5.0% a year, respectively. The net decline in North Karelia was 71 deaths/100,000 men. The decline in mortality from all causes was also appreciable in both sexes in North Karelia, but it did not differ significantly from national trends. PMID- 3094778 TI - Hepatic cholestasis induced by trimethoprim. PMID- 3094779 TI - Possible interaction between heparin and a sulphonylurea a cause of prolonged hypoglycaemia? PMID- 3094780 TI - Carotid artery stenosis exposed by an adverse effect of captopril. PMID- 3094781 TI - Blood disorders associated with pirenzepine. PMID- 3094782 TI - Health and social status of elderly Asians: a community survey. AB - A sample based on general practices was the starting point for a community survey of Asians aged 65 years and over to describe: family structure and social contact; aspects of lifestyle; language and communication; capacity for self care; and knowledge about and use of services. A total of 726 (95% of those approached) old people were interviewed in their own languages. Almost all had been born in India, mainly in Gujarat or the Punjab, but most had come to Britain via east Africa. Over half of the over 75s were not fully independent in basic activities of daily living, and a fifth were occasionally or often incontinent of urine, though these levels of incapacity were little different from those found in the indigenous elderly. Few elderly Asians were aware of social services, such as meals on wheels, home helps, social workers, and particularly chiropody. Language also excluded them: 37% of men and only 2% of women could speak English. Moreover, two thirds of elderly Asian women were illiterate in all languages. Health education initiatives directed at these people must understand these cultural and language barriers and perhaps use alternative methods, such as Asian radio programmes and home videos, in providing information on health and welfare services. PMID- 3094783 TI - Growth of clinical haematology in South Tees Health District 1983-5. AB - A review of the workload of two newly appointed clinical haematologists in a health district with a population of 307,000 showed that the clinical case load increased rapidly in the first two years. The management of patients with blood disorders, which had previously been dispersed among many departments both within and outside the district, was now concentrated within a single unit with occasional referral as appropriate to regional centres. The development of a clinical haematology service in district general hospitals cannot occur without funding and facilities, including suitably located beds for haematology patients and specifically appointed junior medical staff. Highly trained and experienced nursing staff are essential for the management of patients with bone marrow failure; day care facilities and community nursing are also valuable. Changes and developments in the laboratory as a result of these additional clinical activities are also necessary. PMID- 3094785 TI - Public knowledge of AIDS and the DHSS advertisement campaign. PMID- 3094784 TI - Non-invasive femoropopliteal assessment: is that angiogram really necessary? AB - A method of non-invasive preoperative assessment of chronically ischaemic legs was developed that used clinical data and data derived from Doppler ultrasonography to produce a numerical score that could be compared with an angiographic score for stenosis of the popliteal artery trifurcation. The two scoring systems were applied retrospectively to 144 legs after femorodistal bypass. A close correlation was observed (r = 0.89, p less than 0.001), and both systems tended to predict the level of grafting undertaken. A prospective comparison was then made in 81 ischaemic legs that were examined by arteriography; the correlation between the two scoring systems remained close (r = 0.89, p less than 0.001), and the level of bypass was correctly predicted by the non-invasive assessment in 44 of 50 legs that were operated on. Use of the non-invasive assessment subsequently greatly reduced the indications for preoperative arteriography in patients requiring femorodistal vascular reconstruction. PMID- 3094786 TI - Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine treatment? PMID- 3094787 TI - Haem arginate in acute hepatic porphyrias. PMID- 3094788 TI - When things go wrong. PMID- 3094789 TI - Clearance of psoriasis with low dose cyclosporin. PMID- 3094790 TI - Low dose maintenance medication for schizophrenia. PMID- 3094791 TI - Change from porcine to human insulin. PMID- 3094792 TI - Orchidectomy versus oestrogen for prostatic cancer. PMID- 3094793 TI - Morphine intoxication in renal failure; the role of morphine-6-glucuronide. PMID- 3094794 TI - Dietary supplementation in pregnancy. PMID- 3094795 TI - Gonorrhoea in children. PMID- 3094796 TI - The neuropathy of the critically ill. PMID- 3094797 TI - Ceruletide for retained biliary stones. PMID- 3094798 TI - Hospital medical staffing and vocational guidance: teaching hospital juniors' views. PMID- 3094799 TI - Relapse of duodenal ulcer: does it matter which drug is used in initial treatment? PMID- 3094800 TI - A plan for paediatric surgery. PMID- 3094801 TI - Time to scrap creatinine clearance? PMID- 3094802 TI - Effect of optimal glycaemic control with continuous subcutaneous insulin infusion on energy expenditure in type I diabetes mellitus. AB - To assess the role of insulin in the control of body weight energy expenditure was measured by indirect calorimetry in eight patients of normal weight with type I diabetes initially while poorly controlled during conventional insulin treatment and later during optimal glycaemic control achieved by using the continuous subcutaneous insulin infusion pump. Their response to seven days of fat supplementation was also assessed and the results compared with those in eight non-diabetic subjects. After a mean of 5.3 months of continuous subcutaneous insulin infusion the diabetic subjects had gained on average 3.5 kg. In the poorly controlled diabetic state the resting metabolic rate was raised but decreased by a mean of 374 kJ (90 kcal) per 24 hours with optimal glycaemic control. The thermic response to infused noradrenaline was reduced by 59% in the diabetic subjects, was not improved by continuous subcutaneous insulin infusion, but was improved when three of the subjects were given metformin in addition. The diabetic subjects had no abnormality in the thermic response to a meal while taking their usual diabetic diet. During fat supplementation, however, this thermic response was reduced when glycaemic control was poor but not when control was precise. Fat supplementation did not alter the resting metabolic rate or the reduced noradrenergic thermic response in the diabetic subjects. These findings suggest that precise glycaemic control could produce weight gain if energy intake remained unaltered, for diabetic subjects do not compensate for the decrease in metabolic rate by an increase in noradrenergic and dietary thermic responses. Also precise glycaemic control using continuous subcutaneous insulin infusion does not correct all the metabolic abnormalities of diabetes mellitus. PMID- 3094803 TI - Detection of spread of malignant lymphoma to the liver by low field strength magnetic resonance imaging. AB - The accuracy of spin lattice relaxation time (T1) measurement obtained with a low field strength magnetic resonance imager for the detection of spread of malignant lymphoma to the liver was assessed. The results of histological examination obtained at open liver biopsy were compared with liver T1 values in 27 patients with lymphoma. The normal range for T1 was established by scanning 61 healthy volunteers. Magnetic resonance imaging was highly sensitive in detecting hepatic lymphoma, all seven patients with liver lymphoma proved by biopsy having considerably higher T1 values. Specificity was less good. Five out of 20 patients with no histological evidence of hepatic lymphoma had abnormal T1 values. this level of sensitivity is considerably better than that reported for other imaging methods and contrasts with the results of one previous study using a different magnetic resonance system. Low field strength magnetic resonance imaging may prove to be a useful screening test in patients with lymphoma. The presence of a normal liver T1 seems to be a reliable guide to the absence of hepatic disease. PMID- 3094804 TI - Improvement in bronchial hyper-responsiveness in patients with moderate asthma after treatment with a hypnotic technique: a randomised controlled trial. AB - A prospective, randomised, single blind, and controlled trial of a hypnotic technique was undertaken in 39 adults with mild to moderate asthma graded for low and high susceptibility to hypnosis. After a six week course of hypnotherapy 12 patients with a high susceptibility score showed a 74.9% improvement (p less than 0.01) in the degree of bronchial hyper-responsiveness to a standardised methacholine challenge test. Daily home recordings of symptoms improved by 41% (p less than 0.01), peak expiratory flow rates improved by 5.5% (p less than 0.01), and use of bronchodilators decreased by 26.2% (p less than 0.05). The improvement in bronchial hyper-reactivity occurred without a change in subjective appreciation of the degree of bronchoconstriction. A control group 17 patients and 10 patients undergoing treatment with low susceptibility to hypnosis had no change in either bronchial hyper-responsiveness or any of the symptoms recorded at home. This study shows the efficacy of a hypnotic technique in adult asthmatics who are moderately to highly susceptible to hypnosis. PMID- 3094805 TI - Protracted diarrhoea of infancy: evidence in support of an autoimmune variant. AB - Circulating autoantibodies to enterocytes were detected by indirect immunofluorescence in 14 out of 25 patients with idiopathic protracted diarrhoea of infancy. Similar specificities were not found in 50 control children with nongastroenterological disorders. The immunofluorescence pattern was more accentuated on the apical border of mature enterocytes. Enterocyte autoantibodies were mainly of IgG class (13/14), but 11 sera were positive for IgM and IgA classes, and five out of 14 positive sera also had the ability to fix complement. Absorption of sera positive for autoantibodies with an IgA coupled immunoabsorbent did not modify the intensity of the staining, indicating that these antibodies were not directed against secretory IgA. High titres and the complement fixing ability of enterocyte autoantibodies indicated a poorer prognosis despite the use of immunosuppressive drugs. Organ specific and non organ specific autoimmune diseases or corresponding autoantibodies or both were often found in children with enterocyte autoantibodies and their family. These data show the existence of an autoimmune variant of protracted diarrhoea of infancy, despite the rare occurrence of autoimmune diseases in childhood. PMID- 3094806 TI - Fate in intermittent claudication: outcome and risk factors. AB - The fate of 257 consecutive patients (100 women) aged 36-85 years (mean 65) first seen with intermittent claudication in 1977 was analysed after a mean of 6.5 (SD 0.5) years. When first seen none of the patients complained of rest pain or had ulcers or gangrenous lesions on the feet. At follow up 113 of the patients (44%) had died. Causes of death were no different from those in the general population. Mortality was twice that of the general population matched for age and sex. Mortality among the men was twice that among the women. In men under 60 mortality was four times that expected. The rate of clinical progression of the arteriosclerotic disease (that is, rest pain or gangrene) of the worst affected leg was 7.5% in the first year after referral. Thereafter the rate was 2.2% a year. An ankle systolic blood pressure below 70 mm Hg, a toe systolic blood pressure below 40 mm Hg, or an ankle/arm pressure index below 50% were individually significantly associated with progression of the arteriosclerotic disease. These findings show the importance of peripheral blood pressure measurements in the management of patients with intermittent claudication due to arteriosclerotic disease. PMID- 3094807 TI - Assessment of non-mydriatic fundus photography in detection of diabetic retinopathy. AB - Non-mydriatic retinal photography with later interpretation of the photographs was assessed as a screening method for the detection of diabetic retinopathy; when compared with an ophthalmologist's clinical assessment in a random group of 62 diabetic patients it was accurate (false negative 6.8%, false positive 2%) and sensitive (sensitivity 96%, specificity 98%). The assessment of further management required based on analysis of the photographs was 96.5% in agreement with the further management suggested by the ophthalmologist after direct clinical assessment of the patient. If this technique were used to screen patients in a typical diabetic clinic the predicted positive accuracy rate would be 84% and the predicted negative accuracy rate 99.5%. PMID- 3094809 TI - Endoscopic removal of pharmacobezoar of slow release theophylline. PMID- 3094808 TI - Acute renal failure after overdose of labetalol. PMID- 3094810 TI - Imaging in rheumatoid arthritis using liposomes labelled with technetium. PMID- 3094812 TI - What is a good GP? PMID- 3094811 TI - Randomised trial of treatment of hypertension in elderly patients in primary care. AB - A randomised trial of the treatment of hypertension in 884 patients aged 60 to 79 years at the onset showed a reduction of 18/11 mm Hg in blood pressure over a mean follow up period of 4.4 years. The principal antihypertensive agents were atenolol and bendrofluazide. There was a reduction in the rate of fatal stroke in the treatment group to 30% of that in the control group (95% confidence interval 11-84%, p less than 0.025). The rate of all strokes (fatal and non-fatal) in the treatment group was 58% of that in the control group (95% confidence interval 35 96%, p less than 0.03). The incidence of myocardial infarction and total mortality was unaffected by treatment. Questionnaires completed by the patients and their relatives failed to identify any differences in symptoms that were likely to be due to treatment. PMID- 3094813 TI - The general surgeon who cares for children. PMID- 3094814 TI - Rectal mass of prostatic origin: a possible trap for general surgeons. PMID- 3094816 TI - Differences among Asian patients. PMID- 3094815 TI - Pelvic pain in women. PMID- 3094818 TI - Doctors and the drug industry. PMID- 3094817 TI - Desensitising vaccines: an allergist's view. PMID- 3094819 TI - Combination therapy in prostate cancer. PMID- 3094821 TI - Murdering while asleep. PMID- 3094820 TI - A star treatment for digoxin overdose? PMID- 3094822 TI - Why do patients still die from paracetamol poisoning? PMID- 3094823 TI - Intermittent hypoxia in patients with unexplained polycythaemia. PMID- 3094824 TI - A simple grading system to guide the prognosis after hip fracture in the elderly. PMID- 3094825 TI - Normal pressure hydrocephalus. PMID- 3094826 TI - Childhood leukaemia and radioactive discharges at Sellafield. PMID- 3094827 TI - Prenatal diagnosis of Turner's syndrome: what to tell parents. PMID- 3094828 TI - Severe head injury: the first hour. PMID- 3094829 TI - Time course of the reduction of GABA terminals in a model of focal epilepsy: a glutamic acid decarboxylase immunocytochemical study. AB - Immunocytochemical localization of glutamic acid decarboxylase (GAD), the synthesizing enzyme for the neurotransmitter gamma-aminobutyric acid (GABA), has been used to study the time course of the decrease in putative GABAergic synaptic terminals that occurs in an alumina gel-induced model of focal epilepsy. Monkeys were studied at progressive intervals following unilateral application of alumina gel to sensorimotor cerebral cortex, and were categorized into 3 different experimental groups depending upon their clinical status. These groups respectively exhibited: (1) no abnormal bioelectrical (EEG and ECoG) activity; (2) abnormal bioelectrical activity, but no clinical seizures; and (3) both abnormal bioelectrical activity and clinical seizures. Normal and sham-operated monkeys were also studied. The amounts of GAD-positive terminal-like structures were determined on control and experimental sides of motor cortex (layer V) of all specimens with an image analysis system. This quantitative study revealed that monkeys from the 3 experimental groups showed reductions of GAD-positive terminals on the experimental cortical side, with greater losses occurring at progressively longer times following alumina gel implants. Statistical tests showed that there were no significant cortical side differences for the normal and sham groups, but that cortical side variations were significantly different for each of the 3 experimental groups. Conventional electron microscopy of an early experimental stage revealed degenerating axon terminals in layer V of motor cortex, as well as phagocytosis of degenerating material and astrogliosis. Similar findings were obtained from a chronically epileptic specimen, except that degenerating terminals were observed less often and fibrous astrocytic scarring was more prevalent, especially surrounding the somata of pyramidal neurons. The main conclusion drawn from the results of this investigation is that significant decreases of GAD-positive terminals occur prior to the onset of clinical seizures, and this is consistent with a causal role for a loss of GABAergic innervation in the development of seizure activity in this primate model of focal epilepsy. PMID- 3094830 TI - Spread of scrapie agent to the central nervous system: study of a rat model. AB - Invasion of scrapie agent into the central nervous system (CNS) was studied in rats following intracerebral and peripheral inoculation, the latter by injection into intact or transected sciatic nerve. Comparison of sleep-wakefulness alterations, neuropathological features, and time lag of electroencephalographic and clinical signs in the 3 groups suggests that hematogenous spread of infection to the CNS may predominate over neural transport, and that peripheral inoculation may closely approximate natural infection. PMID- 3094831 TI - Partial protection by desmethylimipramine of the mesocortical dopamine neurones from the neurotoxic effect of 6-hydroxydopamine injected in ventral mesencephalic tegmentum. The role of noradrenergic innervation. AB - As shown in the rat by estimation of dopamine (DA) and noradrenaline (NA) levels, bilateral 6-hydroxydopamine (6-OHDA, 4 micrograms/microliter) lesions made in the ventral mesencephalic tegmentum (VMT) destroy both ascending DA and NA neurones. Pretreatment of rats with desmethylimipramine (DMI, 30 mg/kg, i.p.), 30 min before microinjection of 6-OHDA into the VMT partially prevented the destruction of the DA neurones innervating the prefrontal and cingulate cortices but not those innervating subcortical structures (nucleus accumbens, olfactory tubercles, septum). Results obtained from the prefrontal cortex of rats with extensive lesions of the ascending NA neurones performed 15 days prior to the 6-OHDA lesions of the VMT in the presence of DMI, imply that NA innervation of the VMT seems to be required for DMI to protect the cortical DA neurons from the neurotoxic effect of 6-OHDA. PMID- 3094832 TI - Modifications in the responsiveness of rat ventrobasal thalamic neurons at different stages of carrageenin-produced inflammation. AB - The present study was aimed at analyzing the responsiveness of the ventrobasal (VB) thalamic neurons in rats presenting with a hyperalgic carrageenin-produced inflammation. The following were studied: the responses of the same VB neuron, before and 15-145 min after the plantar injection of carrageenin in a part of its receptive field (RF) (acute phase); the responses of VB neurons located in the thalamus contralateral to the hyperalgesic inflamed paw, 24-96 h after the injection (subacute phase); and the effect of a local anesthetic injected in the inflamed paw, and that of an intravenous injection of Aspirin, on neuronal response modifications. Responses of VB neurons initially activated by light tactile stimuli (group 1; n = 4) and by moderate joint stimulation (group 3; n = 4) were not modified in the early period following the carrageenin injection. By contrast, in the first few minutes following the injection. VB neurons exclusively driven by noxious mechanical and thermal stimuli (group 2; n = 23), exhibited a clear enhancement of their responses, which persisted during the observation period. These modifications were also observed for responses obtained from part of the RF remote from the injection site; moreover there was an extension of the RF to areas distant from the injured paw. The local injection of an anesthetic (Xylocaine) in this paw, suppressed the modifications of responses of group 2 neurons, elicited not only from the injected paw, but also from the remote parts of the RF. At this time Aspirin was almost inefficient (even at the dose of 100 mg/kg) on responses of these group 2 neurons. In the subacute phase responses of 72 somatosensory neurons were analyzed. Twenty-five of 72 responded to rapid repetitive light tactile stimulation applied on a small contralateral RF (group 1); their responses were similar to those encountered in a normal situation. Thirty-three of 72 neurons responded to intense mechanical stimuli such as pinches (group 2). For half of them the response characteristics were similar to those described in the normal rat; for the other half responses appeared 'faded': short duration; absence of after-discharge; poor reproducibility. Fourteen of 72 neurons responded to moderate stimulation of the joints, deep tissues and/or surrounding cutaneous areas of the inflamed paw (group 3). Their RF was mostly unilateral, i.e. contralateral to the recording site; the responses were sustained during the stimulation but rarely exhibited after-discharge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3094833 TI - Quantitative changes in morphological parameters in the developing visual cortex of the marmoset monkey. AB - Several quantitative morphological parameters were measured during postnatal development in area 17 of the marmoset monkey (Callithrix jacchus). In a series of 14 animals, at ages from birth to adulthood, we studied changes in the thickness, surface area and volume of area 17, as well as the neuronal and glial numerical densities, and total numbers. We found evidence for a rapid increase in thickness, area and volume, culminating between 6 weeks and 6 months postnatally, and then decreasing. The adult values are close to those observed in one-month old animals. The overshoot in thickness and volume is greatest in layers II, III, IVa and IVc. The neuronal density shows a trend which is opposite to that of volume, and therefore the total number of neurons is constant postnatally, ca. 38 million neurons in area 17 of one hemisphere. The number of glial cells approximately doubles during the first postnatal month and remains stable afterwards, so that in the adult, there is one glial cell for two neurons. Morphological development of area 17 in this New World monkey is similar to that reported in Old World monkeys, as are the adult values for neuronal and glial densities. PMID- 3094834 TI - The amine accumulation-producing capacity of 6-hydroxydopamine and its neurochemical specificity. AB - There was considerable research during the 1970's addressing the problem of the neurospecificity of 6-hydroxydopamine (6-OHDA). Despite the numerous attempts to define the criteria governing the use of this drug in experimental paradigms, some believed that specific damage to catecholamine (CA)-containing neurones could be achieved only by controlling the dose injected, while others claimed that the neurotoxic effect that this drug had on non-CA systems was so severe that it contraindicated its use experimentally. The issue still remains unresolved. In the present study, we examined the degree of neurochemical specificity produced by 6-OHDA or radiofrequency (RF) lesions by comparing the quantity of amine accumulation to the amount of physical damage at the lesion site (termed non-specific damage, NSD) which each technique produced. The volume of NSD produced by 6-OHDA (2 microliter of 8 micrograms/ul) was significantly less than that produced by large RF lesions (60 degrees C for 50 sec) both of which has a similar effect on the regulation of short term body weight. Both types of lesions produced similar quantities of amine accumulation. Smaller RF lesions (45 degrees C for 30 sec) produced the same amount of NSD as did 6-OHDA but significantly less amine accumulation and had no effect on body weight regulation. The ratio of NSD to amine accumulation in 6-OHDA treated rats was 3/1 while large and small RF lesions produced a NSD/accumulation ratio of 15/1. The present results reveal that the neurochemical specificity of 6-OHDA is several magnitudes greater than with RF lesions, when using the criteria as defined in the present experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3094835 TI - Astrocyte responses to dopaminergic denervations by 6-hydroxydopamine and 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine as evidenced by glial fibrillary acidic protein immunohistochemistry. AB - Astrocytic responses to dopaminergic denervation by two widely used dopamine neurotoxins, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) were monitored using immunofluorescence with antibodies against glial fibrillary acidic protein (GFA) while neurofilament (NF) antibodies were used to monitor neuronal disturbances. Following stereotaxic injection of 6 OHDA into the nigrostriatal dopamine bundle in rats, an increased amount of GFA immunoreactivity in striatum was detectable after 24 hours and remained after one month. Retrograde degeneration of nigral neurons led to gliosis in the cell body area. At the site of injection, astrocytes were destroyed and NF-immunoreactivity increased. New astrocytes invaded the injection area during the first month after injection. MPTP given systemically to mice in a dose that causes marked dopaminergic denervation of striatum also caused marked increases of GFA immunoreactivity in striatum. These changes were larger in C57 BL/6 mice, known to be more sensitive to MPTP, than in N.M.R.I. mice, which are less sensitive to MPTP. The glial responses to MPTP-induced dopaminergic denervation did not occur when the dopamine neurotoxic effects were prevented by pretreatment with nomifensine or pargyline. It is concluded that dopaminergic denervation by neurotoxins causes rapid and profound changes in striatal astrocytes characterized by increased GFA-immunoreactivity. These changes remained up to a month after denervation and should be taken into account when functional consequences of dopaminergic denervations are discussed. PMID- 3094836 TI - A rapid purification of synapsin I: a neuron specific spectrin binding protein. AB - We have developed a one chromatographic step isolation protocol for the neuron specific protein synapsin I. This procedure results in a yield of 80 micrograms/g brain, which is ten fold better than the highest yield yet reported for this protein. The authenticity of the synapsin I isolated by this procedure is demonstrated by comigration with authentic synapsin I on SDS-polyacrylamide gels, crossreactivity with antibody specific against synapsin I, and nearly identical two dimensional chrymotryptic iodopeptide maps of authentic synapsin I and the protein purified by this protocol. Synapsin I isolated by this procedure retains its functional properties, demonstrated by the ability of synapsin I to stimulate the formation of a brain spectrin(240/235)/synapsin I/F-actin ternary complex as determined by a low shear falling ball viscometry assay. This novel protocol therefore has the advantage of being a rapid, high yield procedure that retains the functional properties of synapsin I. PMID- 3094837 TI - Prostaglandin involvement in the evoked release of D-aspartate from cerebellar mossy fiber terminals. AB - Isolated cerebellar glomeruli, containing mossy fiber terminals, were used to investigate the mechanisms involved in the evoked release of acid amino acids. The glomeruli contain a high affinity uptake system for D-aspartate, with a KT of 384 pmol/mg protein/min and the incorporated D-[3H]aspartate was released in response to various depolarizing agents, as well as exogenous arachidonic acid and prostaglandins. There was a marked inhibition of the release evoked by high K+ and exogenous arachidonate when the cyclooxygenase inhibitor ibuprofen was present. Also, exposure of the glomeruli to depolarizing conditions resulted in an increase in the amount of unesterified [3H]arachidonate. It appears that accumulation of unesterified arachidonate and subsequent production of prostaglandins are involved in the evoked release of the acidic amino acids from cerebellar mossy fiber terminals. PMID- 3094838 TI - Effects of glycosylation inhibitors on the frog retina. AB - Effects of the intraocular injection of three inhibitors of glycosylation (tunicamycin, castanospermine, and swainsonine) on the rhodopsin content and the integrity of disc membranes in frog retina were studied. The administration of 10 or 100 micrograms of tunicamycin resulted in a 78% loss of rhodopsin in the frog retina which also exhibited a significant reduction in the length of photoreceptor outer segments (as examined under light microscope). This suggests that the synthesis and/or insertion of rhodopsin into the disc membrane is inhibited by tunicamycin. In contrast, injections of up to 250 micrograms of castanospermine and swainsonine resulted in neither a decrease in rhodopsin content nor a change in the length of photoreceptor outer segments. Examination of retinal tissue homogenates for alpha Mannosidase and alpha-Glucosidase activities revealed homogenates for alpha Mannosidase and alpha-Glucosidase activities revealed these hydrolase activities to be significantly decreased (70%). We suggest the possibility that specific oligosaccharide processing reactions may not be required for the insertion of rhodopsin and subsequent assembly of disc membranes in frog photoreceptors. PMID- 3094839 TI - Role of ornithine decarboxylase and the polyamines in nervous system development: a review. AB - Development of nervous tissue is controlled, in part, by the ornithine decarboxylase (ODC)/polyamine system. Each brain region possesses a unique ontogenetic pattern for ODC, with highest levels of the enzyme associated with periods of most rapid growth. For this reason, perturbation of the ODC profile has proven useful in examinations of teratologic mechanisms and detection of adverse environmental effects during development. More recently, the replication of neuronal cells in developing brain has been shown to require the maintenance of polyamine levels and consequently, depletion of polyamines by alpha difluoromethylornithine (DFMO, an ODC inhibitor) arrests brain cell maturation. DFMO also interferes with neuronal migration, axonogenesis and synaptogenesis, leading to disruption of the cytoarchitectural organization of brain structures: these results imply a similarly important role for polyamines in post-replicative events. Indeed, [3H]DFMO-autoradiographic localization of ODC in developing cerebellar lamina indicates high levels of activity associated with neuropil, areas of axonal outgrowth, and post-mitotic granule cells. Axonal outgrowth during regeneration after nerve damage in the mature nervous system may display some of the same characteristics as in developing neurons, suggesting that the two processes share common polyamine-dependent mechanisms. PMID- 3094840 TI - [Absence of a connection between Alzheimer's disease and complement markers]. AB - The hypothesis of a linkage between Alzheimer's disease (AD) (presenile dementia) and the complement components C2, C4, Bf linked to the Major Histocompatibility Complex has been investigated in a large family originating from Calabria, in which AD is transmitted as an autosomal dominant monogenic mendelian trait. The analysis of complotypes of 33 members of a pedigree, from which 10 individuals are affected, allowed to demonstrate that there wasn't any linkage between AD and those markers. Furthermore, no complete or partial deficiency in the C2, C4, Bf components has been observed in affected patients. PMID- 3094841 TI - [Increase of paradoxical sleep, induced by injection of ibotenic acid in the ventrolateral posterior hypothalamus in the cat]. AB - The intratissular injection of ibotenic acid into the ventrolateral part of the posterior hypothalamus induced a dramatic biphasic and transient hypersomnia immediately after disappearance of the anaesthesia (14 to 24 hrs. after injection). The duration of hypersomnia was related to the dose of neurotoxin injected. Its first period was characterized by an increase in paradoxical sleep (PS) (300%). Then, during the second phase, PS disappeared and there was a subsequent increase of slow wave sleep (SWS) (60%). Finally, on the third day, all cats recovered control level of PS and SWS. PMID- 3094842 TI - [Pathogenic antibodies in systemic lupus erythematosus: anti-LAMP antibodies]. AB - We recently demonstrated that a monoclonal anti-DNA antibody, spontaneously produced in lupus B/W mice, recognizes the same protein(s) at the surface of several human cell types involved in lupus pathogenesis including normal human erythrocytes, normal platelets and rat neuronal tissue. This cell-surface protein(s) cross-react(s) with double-stranded DNA. We suggest to call this protein(s) LAMP [lupus associated membrane protein(s)]. Here we show that: immunoglobulins eluted from kidneys of autoimmune MRL/lpr/lpr mice strongly react with LAMP. Anti-LAMP antibodies are present in large amount in MRL/lpr and B/W mice sera. Anti-LAMP are present in 25 out of 25 human SLE sera ranged as SLE on the basis of revised American Rheumatism Associated classification. Interestingly, two of these sera did not display anti DNA anti-body activity. Taken together, these results strongly suggest a role of LAMP in the pathogeny of SLE. PMID- 3094843 TI - [Structural characteristics and innervation of chromaffin tissue in the adrenal gland of the axolotl]. AB - Each adrenal gland of the Axolotl consists of a strip lying all along the medio lateral edge on the ventral surface of the kidney. The gland is composed of interrenal cells (IC) and chromaffin cells (CC). The IC contained a great number of pleomorphic lipid droplets, smooth endoplasmic reticulum and elongated mitochondria with tubulo-vesicular cristae. Two types of CC, always disposed in clusters and exhibiting long cytoplasmic processes were described according to the electron density, size and shape of granules distributed in their cytoplasm; noradrenaline cells (NA) and adrenaline cells (A). The innervation and ultrastructural differences from the adrenal gland of other Anurans were discussed. PMID- 3094844 TI - [Behavior of contractile proteins of rat muscle fibers under microgravity conditions]. AB - Microgravity effects were studied on three muscles: gastrocnemius lateralis, plantaris and diaphragm, after the biocosmos 1514 and 1667 space flights. Results showed a decrease of maximal mechanical activity on both gastrocnemius and plantaris while no modification was observed on diaphragm. Cross-bridge cycling speed was reduced on both gastrocnemius and plantaris. Moreover, a reduced calcium binding affinity appeared in gastrocnemius. PMID- 3094845 TI - [New data on the hormonal requirement of the pregnant rabbit: partial pregnancies and fetal abnormalities after treatment with a hormonal antagonist given at a sub abortive dosage]. AB - Evolution of pregnancy in rabbits depends upon ovarian progesterone. A deficiency in ovarian hormones was observed a long time ago to result either in abortion or in "partial pregnancy" or even in fetal anomalies. Administration to pregnant rabbits, from day 11 on, of a hormonal antagonist known for its anti-progesterone activity, RU486, at a sub-abortive dosage, reproduces the effects of ovarian hormone deficiencies. PMID- 3094846 TI - [Induction of remissions of insulin-dependent diabetes by cyclosporin]. AB - The effect of cyclosporine was evaluated in a double blind placebo controlled trial in 122 recent onset insulin-dependent diabetics. A significantly higher incidence of complete remissions was observed in patients treated with cyclosporine than in those receiving placebo (respectively 24 and 5.8%). The effect was still more clear-cut in patients having presented the highest cyclosporine blood level (37%). These results which have been obtained with modest toxicity demonstrate that cyclosporine induces remission of insulin dependent diabetes and prompt to set up new controlled trials to evaluate the duration of the effect obtained and the potential risks of the treatment. PMID- 3094847 TI - [Insulin-dependent diabetes, an autoimmune disease]. AB - In type I (insulin-dependent) diabetes evidence for an autoimmune process is now fully established. This is also true for a similar disease observed in the NOD mouse and the BB rat. In addition to circulating antipancreatic antibodies, we demonstrated T-lymphocyte mediated cellular immunity in both these diabetic animals and in the human. Immunological abnormalities precede the development of diabetes and may be responsible for beta cell alteration. Evidence for this interpretation appears stronger for cell-mediated than for humoral immunity. However, full demonstration and understanding of the relationship between anti beta cell immunity and beta cell alteration still raise many unresolved problems. PMID- 3094848 TI - [Infection of insect cell lines by the HIV virus, an agent of AIDS, and a demonstration of insects of African origin infected by this virus]. AB - The etiological agent of AIDS known as HIV has been shown to bind on different insect cell lines including Drosophila, Mosquito, Ceratitis; and his DNA to be integrated in the cellular genome, but no expression of the viral genome was detected in those cells. None of the human lymphocytes markers is expressed at the surface of the insect cells. HIV proviral DNA has been also found in various insects from Central Africa (Zaire and Central Africa Republic) but not similar insects from the Paris area. These data suggest that insects could be a reservoir or a vector for the AIDS virus. PMID- 3094849 TI - [Effect of ryanodine on the electrical and mechanical activity of frog atrial fibers]. AB - The effect of ryanodine on the action potential, slow inward current and mechanical activities of frog atrial fibres was studied by means of the double sucrose gap technique. Ryanodine was shown to reduce the amplitude of the slow inward current, to cause an intracellular Ca accumulation and to decrease the tonic component of the tension. PMID- 3094850 TI - [Localization of cholinergic neurons in the cat lower brain stem]. AB - The localization of cholinergic neurons in the cat lower brain stem was determined immunocytochemically with a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme. ChAT-positive neurons were observed in four major cell groups: cranial nerve motor and special visceromotor neurons: parasympathetic preganglionic visceromotor neurons; neurons located in the ponto-mesencephalic tegmentum including area X (or pedunculopontine tegmental nucleus), nucleus laterodorsalis tegmenti (Ldt) of Castaldi, and peri-locus coeruleus alpha (peri-alpha); and neurons located in nucleus reticularis magnocellularis (Mc) and adjacent nucleus reticularis gigantocellularis (Gc) of the medulla. PMID- 3094851 TI - [Detection of Clostridium difficile and its clinical significance]. PMID- 3094852 TI - [Epidemiologic surveillance of acute respiratory infection (ARI) in children]. PMID- 3094853 TI - [Trial formulation of a mental development testing scale for infants 0 to 3 years using combined longitudinal and sectional studies]. PMID- 3094854 TI - [Blood cholesterol levels of 1263 healthy children]. PMID- 3094855 TI - [Clinical analysis of 28 cases of infection by mycoplasma pneumoniae]. PMID- 3094856 TI - [Diagnostic value of the relative width of the action potential-summating potential wave in Meniere's disease]. PMID- 3094857 TI - [Clinical use of acoustic uterosalpingography with hydrogen peroxide]. PMID- 3094858 TI - [Right ventricular function during left heart bypass evaluated by two-dimensional echocardiography]. PMID- 3094859 TI - [Sleep hypoxemia and oxygen treatment in COPD]. PMID- 3094860 TI - [Genetic epidemiology of liver cancer: estimation of the segregation ratio and heritability]. PMID- 3094862 TI - [Histochemical study on nonspecific esterase in large intestine carcinoma]. PMID- 3094863 TI - [Therapeutic drug monitoring (TDM) of phenytoin]. PMID- 3094861 TI - [Circadian rhythm of the glucocorticoid receptor in normal human leukocytes]. PMID- 3094864 TI - [Rational phenytoin therapy: a method for individualizing dosage]. PMID- 3094865 TI - [Clinical significance of the pharmacokinetic determination of theophylline]. PMID- 3094866 TI - [Pharmacokinetic analysis of amiodarone]. PMID- 3094867 TI - [Preventive effect of an extract of A. Nerinifolium Bak on experimental atherosclerosis]. PMID- 3094868 TI - [Sonographic diagnosis of hydatid disease of the liver]. PMID- 3094869 TI - [Value of the triiodothyronine suppression test with serum T4 and thyroid 131I uptake as indexes in judging the prognosis of Graves' disease]. PMID- 3094871 TI - [Experience in treating 20 cases of postmenopausal advanced breast cancer]. PMID- 3094870 TI - [Giardia lamblia infection in the gerbil (Meriones unguiculatus): an animal model]. PMID- 3094872 TI - [Immunoassay in therapeutic drug monitoring]. PMID- 3094873 TI - [Advanced breast cancer treated with aminoglutethimide]. PMID- 3094874 TI - [Creation of an artificial anus in the perineum after a radical Miles operation]. PMID- 3094875 TI - [Effect of oral ZnSO4 on urine copper and blood trace elements in 60 patients with Wilson's disease]. PMID- 3094876 TI - [Selective bronchial arteriography and therapeutic infusion]. PMID- 3094877 TI - [Diagnosis and X-ray examination of Peutz-Jeghers syndrome]. PMID- 3094878 TI - [Relation between serum pancreatic polypeptide and the pathogenesis of duodenal ulcer]. PMID- 3094879 TI - [Cranial arachnoid granulations]. PMID- 3094880 TI - [Immunocytochemical and electron microscopic study of 40 cases of pituitary prolactinoma]. PMID- 3094881 TI - [Cor triatriatum. Report of 4 surgically treated cases]. PMID- 3094882 TI - [Transfusion of fetal liver cells in the treatment of hematologic disease]. PMID- 3094883 TI - [Hypoparathyroidism and basal ganglion calcification]. PMID- 3094884 TI - [Endoscopic microwave treatment of gastric bleeding from mucosal injury]. PMID- 3094885 TI - [Use of computers in 542 cases of blood-gas and acid-base analyses]. PMID- 3094886 TI - [Detection of serum hepatitis B core antigen and its value in the prevention and treatment of hepatitis B virus infection]. PMID- 3094887 TI - [Removal of kidney stones by percutaneous nephrostomy]. PMID- 3094888 TI - [Occupational asthma induced by sisal hemp]. PMID- 3094889 TI - [Classifying renin activity and angiotensin II levels in essential hypertension (clustering analysis)]. PMID- 3094890 TI - [Etiologic and clinical study on infantile pneumonia]. PMID- 3094891 TI - [A preliminary study on the relation of heredity to lifespan]. PMID- 3094892 TI - [Use of cryoincision using a cryogenic knife in the treatment of skin diseases]. PMID- 3094893 TI - [Arteriolar vasomotion and low-frequency wave movement]. PMID- 3094894 TI - [Effect of ligustrazine and salvia miltiorrhiza on microcirculation in the hamster cheek pouch]. PMID- 3094895 TI - [Microvascular changes in experimental oral leukoplakia]. PMID- 3094896 TI - [Detection and preliminary studies of the "small double capsid" virus]. PMID- 3094897 TI - [Crystallinity of hydroxyapatite in the callus during spontaneous healing of fractures]. PMID- 3094898 TI - [Determination of anti-Scl-70 antibody and its clinical significance in progressive systemic sclerosis]. PMID- 3094899 TI - [Sonographic diagnosis of a tumor after high-frequency hyperthermy]. PMID- 3094900 TI - [Determination of rifampin, rifamdin and rifocin concentrations in the CSF of 71 patients with tuberculous meningitis]. PMID- 3094901 TI - [Renin classification based on epidemiologic and biochemical factors in essential hypertension]. PMID- 3094902 TI - [Comparative analysis of the pathologic and clinical diagnosis in 615 adult autoptic cases]. PMID- 3094903 TI - [Etiology and pathogenesis of "farmer's lung"]. PMID- 3094904 TI - [Detection of antistreptolysin O antibody by dot-immunobinding assay]. PMID- 3094905 TI - [Subtotal splenectomy in liver cirrhosis]. PMID- 3094906 TI - [Activity of T lymphocytes in gastric and colonic cancers and in early gravid decidua]. PMID- 3094907 TI - [Clinicopathologic study on 241 cases of mucoepidermoid carcinoma of the salivary glands]. PMID- 3094908 TI - [Analysis of 169 cases of early-stage gastric carcinoma]. PMID- 3094909 TI - [External counterpulsation in the treatment of 56 cases of acute myocardial infarction]. PMID- 3094910 TI - [Topographic diagnosis of epilepsy]. PMID- 3094911 TI - [Effect of Ligusticum wallichii and Radix astragali on microcirculation in the hamster cheek pouch]. PMID- 3094912 TI - [Abnormal function of peripheral lymphocytes in producing interleukin 2 and immune interferon in patients with hepatitis B]. PMID- 3094913 TI - [Serum and red cell folate levels in pregnant women]. PMID- 3094914 TI - [A preliminary study on the changes of plasma sex hormone level in rats with myocardial infarction]. PMID- 3094915 TI - [Analysis of 40 cases of asthma induced by common foods in China]. PMID- 3094916 TI - [Hepatolithiasis with the appearance of biliary sandstone in systemic circulation]. PMID- 3094917 TI - [Preliminary results of microsurgical reversal after tubal sterilization]. PMID- 3094918 TI - Alert: perforation of the heart and vessel by central venous catheters inserted for CVP monitoring and TPN therapy. PMID- 3094919 TI - Respiratory depression following epidural morphine: a clinical study. AB - Thirteen post-thoracotomy patients were entered into a double-blind, randomized clinical trial comparing the effects of epidural morphine (Group E) and intravenous morphine (Group I) on postoperative respiratory depression. Postoperative respiratory depression was assessed for 24 hours by (a) PaCO2 at 2, 6, 12 and 24 hours (b) hourly assessment of respiratory rate (RR) (c) presence of respiratory rate of less than ten breaths per min for greater than 5 min (SRR) (d) hypopnoea/apnoea (H/A). RR, SRR, and H/A were measured using respiratory inductive plethysmography. PaCO2 was significantly elevated at 2, 6 and 12 hours in Group E and only at two hours in Group I. One of five patients in Group I had a single episode of SRR whereas five of eight patients in Group E had multiple episodes of SRR. None of the patients in Group I had H/A episodes, in contrast to six of eight in Group E who had numerous H/A episodes post-operatively. This difference was statistically significant. Multiple doses of epidural morphine produce an insidious and unpredictable change in respiratory pattern. Electronic monitoring is useful to assess those at risk of overdose and possible respiratory arrest. PMID- 3094920 TI - Epidural meperidine analgesia after cardiac surgery. AB - Epidural meperidine (1 mg X kg-1) was administered for relief of sternal pain to ten patients, at a mean of 24.8 hours after infusion of high dose fentanyl for cardiac surgery. Lung function, cough, pain score, somnolence, respiratory rate, PaCO2, pulse and blood pressure were studied before and for six hours after analgesic administration. Following epidural meperidine, four of ten patients were pain-free, and three had only minimal pain. Duration of analgesia was 8.8 +/ 4.9 hours. Cough score was significantly improved for five hours. Postoperatively vital capacity was approximately 40 per cent, and FEV1 was approximately 55 per cent of the preoperative value. There was no significant change in FEV1 or vital capacity, following analgesia with epidural meperidine. The somnolence score increased in seven patients. In the first two hours after epidural meperidine, three patients exhibited a fall in their respiratory rate, one had a PaCO2 greater than 45, and two of these patients had marked hypotension. These side effects are easily treated without mechanical or pharmacological support, and do not preclude the use of epidural meperidine after a high dose fentanyl anaesthetic. PMID- 3094921 TI - Flow requirements for the Bain breathing circuit during anaesthesia for caesarean section. AB - We studied the relationship between arterial carbon dioxide tension (PaCO2) and fresh gas flow (FGF) during use of the Bain breathing circuit for Caesarean section anaesthesia. Thirty-one patients undergoing Caesarean section were anaesthetised using the Bain circuit with intermittent positive pressure ventilation. The PaCO2 were measured at FGF of 70 ml X kg-1 X min-1, 80 ml X kg-1 X min-1, and 100 ml X kg-1 X min-1. The FGF requirement to maintain a given PaCO2 during Caesarean section anaesthesia is the same as the requirements for nonpregnant subjects, despite the increase in carbon dioxide production associated with pregnancy. This is probably because the total FGF determined by body weight and given during Caesarean section anaesthesia is 15-20 per cent higher than nonpregnant levels, due to the weight gain associated with pregnancy. A FGF of 100 ml X kg-1 of pregnant weight/min maintains PaCO2 of 4.44 kPa predelivery, which is in the desirable range of PaCO2 during Caesarean section. PMID- 3094922 TI - Improvement in forward cardiac output without a change in ejection fraction during nitroglycerin therapy in patients with functional mitral regurgitation. AB - Left ventricular volumes and forward aortic flow were measured using combined two dimensional echocardiography and doppler cardiography in seven patients with decompensated congestive heart failure and functional mitral regurgitation prior to and during intravenous administration of nitroglycerin. Total stroke volume was calculated from the difference between end-diastolic and end-systolic volumes, and regurgitant mitral volume from the difference between total stroke volume and forward aortic flow. Regurgitant mitral volume fell from 19 +/- 9 to 3 +/- 3 mL/beat (p less than 0.001), while forward stroke volume increased from 35 +/- 8 to 45 +/- 9 mL/beat (p less than 0.001). The changes were well correlated (r = 0.8, p less than 0.001). Total stroke volume decreased from 54 +/- 12 to 48 +/- 6 mL/beat (p less than 0.05), and ventricular end-diastolic volume from 173 +/- 66 to 158 +/- 66 mL (p less than 0.05). Left ventricular ejection fraction did not change significantly: 33 +/- 9% vs 32 +/- 9% (NS). Thus, in patients with severe congestive heart failure and functional mitral regurgitation, intravenous nitroglycerin redistributes blood flow within the heart by decreasing mitral regurgitation and increasing forward aortic flow, without affecting left ventricular ejection fraction. PMID- 3094923 TI - Endothelium-dependent relaxation of rabbit aorta by acetylcholine requires ethylenediaminetetraacetic acid. AB - Experiments were conducted to determine if ethylenediaminetetraacetic acid (EDTA) was essential for the acetylcholine (ACh)-induced relaxation of blood vessels. Isolated rabbit aortic rings were prepared for recording isometric tension. They were maintained in Krebs bicarbonate solution with various concentrations of EDTA. With EDTA concentrations of 0 or 0.003 mM, no ACh-induced relaxation was observed; only the contractile effect of ACh was seen. With 0.03 and 0.30 mM EDTA, ACh induced relaxation with EC50 values of 0.11 and 0.098 microM, respectively. Under the experimental conditions used, EDTA was essential for demonstration of ACh-induced relaxation. PMID- 3094925 TI - Purification and partial characterization of a Vibrio hollisae hemolysin that relates to the thermostable direct hemolysin of Vibrio parahaemolyticus. AB - Hemolysin produced by Vibrio hollisae (Vh-rTDH), which is related to the thermostable direct hemolysin (Vp-TDH) of Vibrio parahaemolyticus, was studied. Vh-rTDH was purified by successive column chromatographies on diethylaminoethyl cellulose and an immunoaffinity column coupled with anti Vp-TDH immunoglobulin. The purified toxin was homogeneous, as demonstrated by conventional and sodium dodecyl sulfate--polyacrylamide gel electrophoresis (PAGE). The molecular weight of Vh-rTDH was slightly smaller than that of Vp-TDH, as determined by sodium dodecyl sulfate--slab gel electrophoresis. Conventional PAGE also showed a difference between Vh-rTDH and Vp-TDH. Vp-TDH and Vh-rTDH showed different lytic activities on erythrocytes from various animals, in particular chicken, sheep, and calf. The hemolytic activity of Vh-rTDH was heat labile when heated at 70 degrees C for 10 min, unlike Vp-TDH. Immunological cross-reactivity between Vh rTDH and Vp-TDH was demonstrated by both the Ouchterlony test and neutralization test. PMID- 3094924 TI - Effects of fasting and food restriction on brown adipose tissue composition in normal and dystrophic hamsters. AB - Fasting for 36-48 h or food restriction (30% reduction of daily food intake for 6 weeks) caused brown adipose tissue (BAT) atrophy in hamsters. Fasting-induced atrophy was characterized by reductions in tissue mass, DNA, protein, and thermogenin. By contrast, food restriction had no effect on tissue cellularity (DNA) but markedly reduced the tissue protein and thermogenin contents. The concentration of thermogenin in isolated mitochondria was unchanged by fasting or food restriction. Dystrophic hamsters had a reduced BAT mass when compared with weight-matched control hamsters. This resulted from a reduction in tissue cellularity since BAT DNA, protein and thermogenin contents were all reduced. The extent of binding of [3H]guanosine diphosphate to isolated mitochondria and their content of thermogenin were similar in normal and dystrophic hamsters. In response to cold exposure, as in normal hamsters, BAT of dystrophic hamsters grew and the tissue thermogenin increased, but the mitochondrial concentration of thermogenin did not change. In response to fasting, in contrast with normal hamsters, there was no significant reduction in BAT DNA in dystrophic animals and the loss of tissue protein was reduced. However, the relative changes in BAT composition during chronic food restriction were similar in normal and dystrophic animals. Thus, reduction in hamster BAT thermogenic capacity during food deprivation may occur by loss of cells and (or)reduction in the tissue protein and thermogenin contents. The extent of protein and (or) DNA loss may be dependent upon the original tissue mass and the severity of food deprivation. PMID- 3094926 TI - Monitoring and avoiding drug and chemical teratogenicity. PMID- 3094927 TI - Perforation of the heart or vena cava by central venous catheters inserted for monitoring or infusion therapy. PMID- 3094928 TI - Cardiac tamponade from central venous catheterization. PMID- 3094929 TI - Toward a better mousetrap. PMID- 3094930 TI - Multiple cytogenetic aberrations in neurofibrosarcomas complicating neurofibromatosis. AB - Four neurofibrosarcomas, from four unrelated patients with Von Recklinghausen's neurofibromatosis, demonstrated multiple cytogenetic aberrations characterized by loss of chromosomes and/or polysomy, as well as multiple structural abnormalities of diverse types. These observations are noteworthy for two reasons. First, the widespread and varied nature of the chromosomal changes indicate that, in at least these instances, the transformation of a benign neurofibroma to a neurofibrosarcoma may well involve a substance having an affect at multiple chromosomal sites. Second, efforts to investigate neurofibrosarcoma pathogenesis using direct analysis of DNA structure and gene activity in neurofibrosarcomas must first take into account the chromosomal distortions characterizing each tumor. PMID- 3094931 TI - Polychlorinated biphenyls, classified as either phenobarbital- or 3 methylcholanthrene-type inducers of cytochrome P-450, are both hepatic tumor promoters in diethylnitrosamine-initiated rats. AB - The cytochrome P-450 isozymes, cytochrome P-450 MC1 and MC2, purified from rats treated with 3-methylcholanthrene (MC), were found by immunohistochemical staining to be strongly induced in the livers of rats treated with 3,3', 4,4' tetrachlorobiphenyl (TCBP), while the cytochrome P-450 isozymes, PB1 and PB2, purified from the livers of rats treated with phenobarbital (PB), were shown to be induced in the livers of rats treated with 2,2', 4,4', 5,5'-hexachlorobiphenyl (HCBP). The latter compound also strongly induced NADPH-cytochrome P-450 reductase. Following induction, all 5 enzymes were located preferentially in the centrilobular and midzonal region of the liver acinus. The influence of these polychlorinated biphenyls (PCBs) on diethylnitrosamine (DEN)-initiated hepatocarcinogenesis was investigated by analyzing the evolution of adenosine triphosphatase-deficient focal lesions. Whereas DEN alone produced very few islets, the administration of either PCB congener (150 mumol/kg, i.p., once weekly over a period of 8 weeks) subsequent to DEN treatment (50 ppm in the drinking water, 10 days) strongly enhanced the number of islets as well as the relative volume of liver occupied by islet tissue. These effects were evident, both 1 and 9 weeks, after cessation of PCB treatment. Unexpectedly the less persistent PCB congener, TCBP, showed a much more potent enhancing effect after the 9 weeks recovery period than did (HCBP). PMID- 3094932 TI - Delayed development of bladder cancer in male SD rats induced with N-nitroso-N butyl-N-(4-hydroxybutyl)amine following concomitant administration of sodium 2 mercaptoethane sulfonate. AB - This study describes the prolonged survival of male SD-rats that bear bladder carcinomas induced either with 44 mg/kg or 28 mg/kg of N-nitroso-N-butyl-N-(4 hydroxybutyl)amine (BBNOH), when daily doses of 350 mg/kg of sodium-2 mercaptoethane sulfonate (mesna) were administered concomitantly. The difference to carcinogen-treated positive controls was highly significant (P = 0.0009 and 0.0013, respectively). Tumor volumes at time of death (P less than 0.005) and frequency of metastases were also reduced in rats that received both compounds in comparison to BBNOH-treated animals. PMID- 3094933 TI - Effect of purified rat and hamster hepatic glutathione S-transferases on the microsome mediated binding of aflatoxin B1 to DNA. AB - Rat and hamster liver cytosolic glutathione (GSH) S-transferases purified by GSH affinity chromatography have been examined for their effects on the microsome mediated binding of aflatoxin B1 (AFB1) to DNA and on the conjugation of AFB1-2,3 epoxide with GSH. Like previous studies with cytosolic preparations (Raj et al. (1984) Carcinogenesis 5, 879), our present study with purified GSH S-transferases showed 2-3-fold more inhibitory activity of AFB1-DNA binding with hamster than that with the rat. Concomitant with the inhibition of AFB1-DNA binding, increase in AFB1-GSH conjugation occurred. Subunit compositions of GSH S-transferases indicate preponderance of Yb and Ya subunits in the hamster and rat, respectively. The role of GSH S-transferases in modulating AFB1-DNA binding and AFB1 induced hepatocarcinogenesis is discussed. PMID- 3094934 TI - Covalent binding of ethylated analogs of 7,12-dimethylbenz[a]anthracene to the DNA of mouse embryo fibroblast 10T1/2 cells. AB - The carcinogenicity of a number of ethylated analogs of 7,12-dimethyl benz[a]anthracene (DMBA) has been previously studied. The covalent binding of these compounds to mouse embryo fibroblast 10T1/2 cell DNA expressed as adducts/10(6) bases, paralleled the original carcinogenicity studies and in decreasing order of potency were DMBA, 7-ethyl-12-methylbenz[a]anthracene (7 Et,12-MeBA), 7-methyl-12-ethylbenz[a]anthracene (7-Me,12-Et), and 7,12 diethylbenz[a]anthracene (7,12-DEBA). The results demonstrate that a major determinant of the carcinogenicity of these compounds relates to their ability to bind to DNA. PMID- 3094935 TI - Open pilot trial of ritanserin in parkinsonism. PMID- 3094936 TI - The effect of penultimate N-acetylgalactosamine 4-sulfate on chondroitin chain elongation. AB - Previous work has shown that odd-numbered oligosaccharides containing nonreducing terminal, non-sulfated N-acetylgalactosamine (GalNAc) or 6-sulfated GalNAc are excellent acceptors for enzymic addition of glucuronic acid (GlcA). However, the presence of a 4-sulfated GalNAc group blocks further addition. We have now used even-numbered oligosaccharides (a mixture of 4-sulfated, 6-sulfated, and non sulfated) as acceptors of [3H]GalNAc to investigate the effect of sulfate residues on the GalNAc in the penultimate position. 3H-Labeled oligosaccharides were partially degraded with chondroitin AC lyase. The labeled trisaccharides, consisting of the added [3H]GalNAc and the nonreducing terminal disaccharides of the oligosaccharide acceptors, were then characterized. Both non-sulfated and mono-sulfated 3H-trisaccharides were observed. However, the 3H-trisaccharides were shown by chromatography with prepared standards to be non-sulfated or to be sulfated only at the 6-position. Thus the oligosaccharides containing a 4 sulfated, penultimate GalNAc at the nonreducing end did not serve as acceptors for [3H]GalNAc. Microsomes from mastocytoma cells, which make only chondroitin 4 sulfate, exhibited the same substrate specificity for exogenous oligosaccharide acceptors as did microsomes from chick cartilage which makes chondroitin 6 sulfate. PMID- 3094937 TI - Interactions of lectins with normal, swainsonine-treated and ricin-resistant baby hamster kidney BHK cells. AB - The aggregation of single-cell suspensions of normal and four ricin-resistant cell lines of baby hamster kidney (BHK) cells by several lectins has been studied by particle counting. Normal BHK cells were aggregated by concanavalin A, Ricinus communis agglutinin and ricin, Abrus precatorius agglutinin, wheat germ agglutinin, and Erythrina cristagalli and Erythrina corallodendron agglutinins. Neuraminidase treatment increased 4-13 fold the aggregation of BHK cells by the latter two lectins, as reported earlier for ricin. After long-term culture of normal BHK cells with swainsonine, an inhibitor of complex N-glycan assembly, the aggregation of cells by each lectin except concanavalin A was much decreased or totally abolished. The lectin-induced aggregation of ricin-resistant cell lines RicR 14, 15, 19, and 21 was very similar to swainsonine treated BHK cells. Aggregation of RicR 15, 19, and 21 cells by Erythrina lectins was increased markedly by neuraminidase treatment of the cells. A smaller effect was obtained with Ric 14 cells. The data reported are consistent with similar hybrid N-glycans being present in swainsonine-treated BHK cells and the ricin-resistant cells. The hybrid structures bind lectins of Ricinus, Abrus, and Erythrina species after desialylation. PMID- 3094938 TI - Branch specificity of beta-D-galactosidase from Escherichia coli. AB - The "branch specificities" of the beta-D-galactosidases from Escherichia coli, jack bean, Aspergillus niger, and human liver were investigated with two branched oligosaccharide substrates, one which forms part of a complex-type biantennary N linked glycan (compound 1) and a structure having blood group I activity (compound 2), respectively. Both substrates were available as radioactive compounds having a known distribution of 3H and 14C label in each of the terminal galactosyl groups, which allowed accurate estimation of the branch specificity of the enzymes from the ratio of 3H and 14C radioactivity in the galactose released by these hydrolases. It was found that the beta-D-galactosidase from E. coli preferentially released the galactosyl group at the 1----3 branch of compound 1 and that the 1----6 branch of compound 2. By contrast, the other beta-D galactosidases investigated showed little or no branch specificity. These results suggest that the branch specificity of the beta-D-galactosidase from E. coli has to be explained from a specific recognition of certain parts of the aglycon of the substrates by this enzyme rather than from a better accessibility of the galactose at one particular branch. PMID- 3094939 TI - Probing acceptor specificity in the glycogen synthase reaction with polymer-bound oligosaccharides. AB - Polymers having maltose and maltotriose side-chains were synthesized by attaching 4-carboxy-2-nitrobenzyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside or 4 carboxy-2-nitrobenzyl O-alpha-D-glucopyranosyl-(1----4)-O-alpha-D-glucopyranosyl O-beta-D- glucopyranoside, respectively, to aminoethyl-substituted polyacrylamide gel beads. Subsequently, the two polymers, and analogous polymers having D glucose and cellobiose side-chains, served in a comparative study as acceptors in the glycogen synthase (UDP-D-glucose: glycogen 4-alpha-glucosyltransferase, EC 2.4.1.11) reaction. Highest transfer (4.2%) was observed for the polymer bearing maltotriose groups. The bound saccharides were then removed by irradiation (greater than 320 nm), and examination of them demonstrated that alpha-D-glucosyl oligomerization in the glycogen synthase reaction had occurred. PMID- 3094940 TI - Characterization of N-acetyl-beta-D-galactosaminyltransferase from guinea-pig kidney involved in the biosynthesis of Sda antigen associated with Tamm-Horsfall glycoprotein. AB - This study reports the catalytic activity of N-acetyl-beta-D galactosaminyltransferase from guinea-pig kidney towards such non-glycoprotein acceptors as small oligosaccharides and glycolipids, having a carbohydrate structure similar to that of the Sda antigen associated with human Tamm-Horsfall glycoprotein. 3'-O-Sialyllactose, but not 6'-O-sialyllactose or lactose, was an effective acceptor of the glycosyltransferase. On the basis of enzymic and chemical treatment of the tetrasaccharide obtained by the transfer of [14C]GalNAc to 3'-O-sialyllactose, we propose that the glycosyltransferase attaches beta-D GalNAc to O-4 of the galactose residue that is substituted at O-3 by sialic acid. The GM3 ganglioside, in which the identical carbohydrate moiety of 3'-O sialyllactose is bound to a ceramide residue, did not serve as an acceptor of the kidney-N-acetyl-beta-D-galactosaminyltransferase and did not behave as a competitive inhibitor of the Tamm-Horsfall glycoprotein in the transferase assay. These results indicate that the hydrophobic moiety in the ganglioside hinders the action of N-acetylgalactosaminyltransferase. Study of the transferase activity towards a heterogeneous glycopeptide species prepared from a Sd(a-) Tamm-Horsfall glycoprotein indicated that guinea-pig kidney enzyme preferentially transferred [14C]GalNAc to the oligosaccharides having a tetraantennary branching-structure. PMID- 3094941 TI - Structure of a new disialoganglioside GD1c from spontaneous murine thymoma. AB - A major mono- and a di-sialoganglioside were isolated and purified to homogeneity from a spontaneous thymoma that occurs in AKR mice. Compositional and methylation analyses and the use of exoglycosidases established the monosialoganglioside to be alpha Neu(2----3)beta Gal(1----3)beta GalNAc(1----4)beta Gal(1----4)Glc(1--- 4)Cer and the disialoganglioside to be alpha NeuAc(2----8)alpha NeuAc(2----3)beta Gal(1----3)beta GalNAc(1----4)beta Gal(1----4)Glc(1----1)Cer (GD1c). A possible pathway for the biosynthesis of this disialoganglioside is presented. PMID- 3094942 TI - Human monoclonal antibody. Construction of stable clones reactive with human breast cancer. AB - A human clone was derived from fusion of a malignant cell line (Ball-1) and peripheral blood lymphocytes from a breast cancer patient in long-term remission. This clone, JDB1, was shown to be a genetically identifiable hybrid, expressing chromosomes unique to each of the parental cell types. The JDB1 clone produces IgG/lambda molecules which are extremely reactive with breast tumor cells, but do not bind to normal breast tissue or other types of malignant tissue. This hybrid was constructed without using the commonly accepted fusion technology which employs 8-azoguanine resistant HAT sensitive malignant fusion partners. Rather a selective fusion procedure was used in which a choice of the most efficient and effective malignant partner could be made prior to fusion. This approach was accompanied by stringent selection of patients as lymphocyte donors. This method has allowed for stable and vigorous growth of clones with a near constant amount of specific immunoglobulin production and a normal diploid chromosome number for over 3 years. PMID- 3094943 TI - Synergistic induction of cytotoxicity in macrophages by murine interferon-gamma and biological response modifiers derived from microorganisms. AB - The ability of recombinant murine interferon-gamma (rMuIFN-gamma) to activate murine macrophages with or without several biological response modifiers (BRM), including synthetic muramyl dipeptide derivatives (MDPs), was investigated. Mouse peritoneal macrophages were activated by rMuIFN-gamma alone to the cytostatic state, but not the cytolytic state. Other BRM as well as bacterial lipopolysaccharide (LPS), including a lyophilized preparation of an attenuated strain of Streptococcus hemolyticus, a cell wall skeleton of bacillus Calmette Guerin and synthetic MDPs, were highly active in generating the synergism with rMuIFN-gamma. Macrophages were endowed with the cytolytic activities by combinations of rMuIFN-gamma and MDP-Lys(L18); the combination of 100 U/ml of rMuIFN-gamma with 10 ng/ml of MDP-Lys(L18) was sufficient to induce cytolytic activities in macrophages. The synergism was observed when the macrophages primed with rMuIFN-gamma were treated with LPS or MDP-Lys(L18), but not when the sequence of treatment was reversed. The cytotoxicity of macrophages induced by rMuIFN-gamma with MDP-Lys(L18) was suppressed by priming with MDP-Lys(L18). The suppressive effect was also observed by priming with LPS in combinations of rMUIFN-gamma and LPS. The reason for the suppression of macrophage activation by priming with LPS and MDP-Lys(L18) is at present unknown. PMID- 3094944 TI - Natural killer and antibody-dependent cellular cytotoxicity in cervical carcinoma patients. AB - Natural killer (NK) cell activity and antibody dependent cell-mediated cytotoxicity (ADCC) was measured in 62 untreated cervical carcinoma patients and 25 normal healthy women, using a short-term chromium release assay. A significant reduction in NK and ADCC activity was observed in disseminated disease than in localized disease, when compared with normal donors. The majority of the patients received radiotherapy and both NK and ADCC activity recovered after therapy. Furthermore, interferon-alpha was demonstrated to augment NK activity of peripheral blood mononuclear cells from healthy donors as well as patients. Also large granular lymphocytes separated on Percoll density gradient were the same in number in both the populations studied, although in cervical cancer there seemed to be a defect in killing activity. PMID- 3094945 TI - Multimodality approach to pericardial imaging. AB - In this chapter, three modalities--computed tomography, nuclear magnetic resonance imaging, and echocardiography--have been discussed. Each of these techniques offers unique advantages in the diagnosis of pericardial disease. Although echocardiography is the least expensive, most sensitive, and least invasive technique for the identification of pericardial effusion, false-positive and negative studies may be encountered. These are often resolved with the use of computed tomography and may be resolved with magnetic resonance imaging. Plain film radiography still has the advantage of identifying pericardial calcifications and will suggest the diagnosis of large pleural effusions at low cost and radiation dose. Exquisite portrayal of cross section anatomy using CT will aid in the diagnosis of multiple small tumor deposits and will clearly identify pericardial thickening. The value of magnetic resonance imaging awaits carefully controlled blinded studies, but its role in characterization of the content of pericardial effusions appears especially promising. PMID- 3094946 TI - The new contrast agents: a perspective. PMID- 3094947 TI - Radiographic and clinical findings in unusual abdominal aortic aneurysms. AB - Atherosclerotic abdominal aortic aneurysms typically present either asymptomatically or with abdominal or back pain. Inflammatory, mycotic, and traumatic aortic aneurysms and aneurysms complicated by venous fistula are less common. The different clinical presentations of these latter aneurysms should raise a suspicion to their diagnosis and appropriate preoperative evaluation. The radiographic and clinical features of inflammatory, mycotic, traumatic, and complicated atherosclerotic aneurysms are presented and discussed. PMID- 3094948 TI - Primary intraaortic malignancy--a case report. AB - Malignant peripheral arterial emboli are extremely unusual. Most reported cases of malignant arterial emboli are secondary to invasion of the systemic circulation by pulmonary malignancies via the pulmonary veins. We report a rare case of a primary sarcoma of the aortic arch that presented as malignant emboli. When confronted by a patient with malignant emboli, a normal chest radiograph, and no evidence of a right-to-left shunt, a primary malignancy of the aorta should be suspected and angiography should be performed. PMID- 3094949 TI - Liver transplant rejection arteritis: serial hepatic arteriography. AB - Two liver transplant recipients underwent serial hepatic arteriography, demonstrating a severe, rapidly progressive arteritis involving the hilar hepatic arteries. Liver biopsies in these patients demonstrated ischemic necrosis as a prominent feature. The angiographic appearance and therapeutic implications of liver transplant rejection arteritis are presented. PMID- 3094950 TI - Embolization of the left gastric artery in the absence of angiographic extravasation. AB - Nine high-risk patients with endoscopic evidence of bleeding from the left gastric artery territory without angiographic extravasation were embolized to prevent rebleeding. Three were embolized with Gelfoam particles, 1 with Gianturco coils, and 5 with Gelfoam plus coils. Three patients rebled; 2 were embolized with Gelfoam only, and the third with coils only. No rebleeding occurred in the 5 patients treated with Gelfoam plus coils. No ischemic complications occurred. We conclude that embolization of the left gastric artery, despite absence of extravasation, is effective in preventing rebleeding in high-risk patients and that both Gelfoam and coils be used. PMID- 3094951 TI - Lymphatic disruption following abdominal aortic surgery. AB - Two cases of abdominal lymphatic disruption following surgery on the abdominal aorta are presented, one causing chylous ascites and the other resulting in a lymphocele. These complications have been only rarely described following abdominal vascular surgery. Both patients responded to percutaneous aspiration without recurrence. The radiologist has a major role in both the detection and management of this complication. PMID- 3094952 TI - Percutaneous management of lymphatic fluid collections. AB - Eight lymphatic fluid collections were drained percutaneously. There were no immediate or late complications. Seven patients had follow-up; 1 required surgical drainage of a residual or recurrent lymphocele, and another had reaccumulated fluid in a lymphocele which was detected on autopsy. The remaining lymphatic collections responded to percutaneous drainage. Percutaneous drainage is safe and can be an effective tool in the management of lymphatic collections. PMID- 3094953 TI - Membranous obstruction of the inferior vena cava associated with intrahepatic portosystemic shunt. AB - Two cases of membranous obstruction of the IVC at hepatic portion associated with intrahepatic portosystemic shunts, which presumably represent the persistent vitelline sinusoids, are presented. The association of these two conditions has not been previously reported and may support the congenital etiology of the membranous obstruction of the IVC. The caval membrane was successfully dilated percutaneously with a balloon catheter in each case. PMID- 3094954 TI - Hemopericardium resulting from attempted internal jugular vein catheterization: a case report and review of complications of central venous catheterization. AB - An unusual case of hemopericardium and presumed fatal cardiac tamponade complicating attempted right internal jugular vein catheterization by the posterior approach is reported. Reports of complications in a series of internal jugular vein catheterizations using various approaches (posterior, central, anterior, supraclavicular) and subclavian vein catheterizations are reviewed. Internal jugular vein catheterization is not necessarily safer than subclavian vein catheterization: numerous factors determine success rate and complication rate in central venous catheterizations. PMID- 3094956 TI - Rupture of an aortic dissection into the pericardium. AB - This case report illustrates the angiographic demonstration of a hemopericardium in aortic dissection. A dense collection of contrast and/or a "halo" sign may be seen in the pericardial cavity. PMID- 3094955 TI - Transcatheter treatment of myelomatous AV shunting causing high-output failure. AB - Intraarterial digital subtraction arteriography (DSA) was performed in a 39-year old man with multiple myeloma, high-output congestive heart failure unresponsive to correction of anemia, and a pelvic bruit suspicious for an arteriovenous malformation. DSA revealed extensive neovascularity of all the visualized skeletal structures with rapid arteriovenous shunting in the pelvis. Temporary embolization of both hypogastric arteries with Gelfoam and autologous clot produced immediate and dramatic clinical relief of the shortness of breath, orthopnea, and hyperdynamic circulation. Following return of symptoms, repeat permanent occlusion with Ivalon and Gianturco coils produced minimal clinical response, but a decrease in cardiac output from approximately 23 L/min to 19 L/min. The etiology of congestive heart failure in myeloma, the implications of the use of intraarterial DSA, and the arteriographic findings in myeloma are discussed. PMID- 3094957 TI - Comparison of diflunisal and acetaminophen with codeine in the management of grade 2 ankle sprain. AB - The emergency physician treats many patients with mild to moderate pain due to musculoskeletal injury. The physician must consider the extent of injury, the patient's medication history, and the potential for abuse when prescribing an oral analgesic. A study was designed to compare the efficacy of two oral analgesics, one containing a narcotic and one nonnarcotic, in relieving mild to moderate pain associated with grade 2 ankle sprain. Forty patients were enrolled- all with moderate pain--and were randomly allocated to treatment with either diflunisal or acetaminophen with codeine. Both analgesic agents were equally effective in relieving the pain. Side effects were experienced by six patients, all of whom were receiving acetaminophen with codeine; none of the patients given diflunisal noted side effects. Global assessments of the efficacy and tolerability of the study drugs showed that 89% of 19 patients given diflunisal and 43% of 21 patients given acetaminophen with codeine considered their respective analgesics excellent or very good. PMID- 3094958 TI - Effectiveness of long-term treatment with pantethine in patients with dyslipidemia. AB - A one-year clinical trial with pantethine was conducted in 24 patients with established dyslipidemia of Fredrickson's types II A, II B, and IV, alone or associated with diabetes mellitus. The treatment was well tolerated by all patients with no subjective complaints or detectable side effects. Blood lipid assays repeated after 1, 3, 6, 9, and 12 months of treatment revealed consistent and statistically significant reductions of all atherogenic lipid fractions (total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B) with parallel increases of high-density lipoprotein cholesterol and apolipoprotein A. The results were equally good in patients with uncomplicated dyslipidemia and in those with associated diabetes mellitus. The authors conclude that pantethine (a drug entity related to the natural compound, pantetheine) represents a valid therapeutic support for patients with dyslipidemia not amenable to satisfactory correction of blood lipids by diet alone. PMID- 3094959 TI - Recording of intracellular Ca2+ from smooth muscle cells by sub-micron tip, double-barrelled CA2+-selective microelectrodes. AB - Novel, double-barrelled Ca2+-selective microelectrodes with tip diameters of approximately 0.1 micron were constructed by using Simon's neutral Ca2+ ligand (ETH 1001). Concentric micropipettes were utilized for the first time for Ca2+ selective microelectrodes in which the Ca2+ ligand was incorporated into a protruding inner pipette, surrounded by an outer reference electrode. In addition, they were made from high resistance aluminosilicate glass tubing (Corning Code 1724). These Ca2+-selective electrodes had linear responses from pCa 3 to pCa 7 in the presence of constant [K+]. They provided on-line observation of changes in intracellular [Ca2+] and in the resting membrane potential in single smooth muscle cells isolated from toad stomach. The mean concentration of intracellular Ca2+ in resting cells was 163.6 +/- 20 nM (+/- SEM, n = 16). Doubling the intracellular Ca2+ level by exposure of cells to elevated [K+] was sufficient to cause shortening. PMID- 3094960 TI - Isolation and characterization of a serine esterase from cytolytic T cell granules. AB - Cytotoxic T lymphocytes and lymphocytes with NK-like activity contain a serine esterase activity which has been localized to their cytoplasmic granules by cytochemistry and subcellular fractionation studies. The serine esterase-specific inhibitor 3H-DFP labels two protein species in the granules. The two proteins, referred to as serine esterases 1 and 2 (SE 1 and SE 2), migrate with Mr of 34-36 kd and 28-30 kd, respectively, under reducing conditions. SE 1 shows trypsin-like activity and has been purified to apparent homogeneity. Under nonreducing conditions, SE 1 has an Mr of 60-66 kd, suggesting that it may consist of two disulfide-linked subunits of 34-36 kd each. SE 1 cleaves fibrin and casein, has a pl greater than 10, and optimal activity at pH 8. The substrate specificity of SE 2 is not known. The serine esterase activity is secreted by lymphocytes that have been stimulated with the calcium ionophore A23187. The serine esterases described here could play an active role in cell-mediated killing. PMID- 3094961 TI - Telomere proteins: specific recognition and protection of the natural termini of Oxytricha macronuclear DNA. AB - The macronuclear DNA in the ciliated protozoan O. nova consists of integral of 10(7) gene-sized DNA molecules, all of which terminate with 20 bp of C4A4 repeats followed by a 3' (G4T4)2 single-stranded tail. Two immunologically distinct proteins of 55 and 26 kd, which are tenaciously, but noncovalently associated with Oxytricha macronuclear DNA termini, have been purified. These proteins protect DNA termini from degradation by the exonuclease Bal31. They also facilitate retention of natural and synthetic telomeric DNAs onto nitrocellulose. The Oxytricha proteins are not simply C4A4-binding proteins. Rather, their efficient binding requires both the 3' single-stranded (G4T4)2 tail and the adjacent duplex region. Thus, these proteins require both the sequence and the structure of natural DNA termini for efficient binding. As such they represent the first described example of telomeric-specific proteins. PMID- 3094962 TI - The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. AB - The isolation of clones encoding the human surface protein T4, and the expression of the T4 gene in new cellular environments, have enabled us to examine the role of this protein in the pathogenesis of AIDS. Our studies support a mechanism of AIDS virus infection that initially involves the specific interaction of the AIDS virus with T4 molecules on the cell surface. This association can be demonstrated on T4+ transformed T and B lymphocytes as well as epithelial cells. Furthermore, the presence of T4 on the surface of all human cells examined is sufficient to render these cells susceptible to AIDS virus infection. Our data suggest that the T4-AIDS virus complex is then internalized by receptor-mediated endocytosis. Finally, we find that the T4 gene is expressed in the brain as well as in lymphoid cells, providing an explanation for the dual neurotropic and lymphotropic character of the AIDS virus. In this manner, a T lymphocyte surface protein important in mediating effector cell-target cell interactions has been exploited by a human retrovirus to specifically target the AIDS virus to populations of T4+ cells. PMID- 3094963 TI - The ras-related YPT1 gene product in yeast: a GTP-binding protein that might be involved in microtubule organization. AB - The 23.5 kd protein product of the ras-related YPT1 gene of S. cerevisiae was found to be essential for cell growth. The loss of YPT1 function, studied in cells with the YPT1 gene on chromosome VI regulated by the galactose-inducible GAL10 promoter, led to arrested cells that were multibudded and exhibited a complete disorganization of microtubules and an apparent loss of nuclear integrity. The YPT protein binds GTP specifically. GTP binding of the protein is essential for its intracellular function. The Asn121----IIe substitution, generated by site-directed mutagenesis, had a dominant lethal phenotype, the expression of the mutant protein led to binucleated cells and abnormal spindles. In contrast to the S. cerevisiae RAS1 and RAS2 gene products, the YPT protein seems to be involved, directly or indirectly, in microtubule organization and function. PMID- 3094964 TI - One heavy chain variable region gene segment subfamily in the BALB/c mouse contains 500-1000 or more members. AB - Nucleic acid hybridization studies suggest that 500-1000 or more heavy chain variable (VH) gene segments related to one VH gene segment (J558) are present in the genome of the BALB/c mouse. The implications of this result regarding the overall size, sequence organization, and evolution of the mouse family of VH gene segments are discussed. PMID- 3094965 TI - Microbiological basis for the use of fosfomycin trometamol as single-dose therapy for simple cystitis. AB - Fosfomycin trometamol (FOT), a new soluble salt of fosfomycin, was developed especially for single-dose treatment in uncomplicated urinary tract infections. In this study, the minimum inhibitory concentrations (MICs) of FOT were measured both in nutrient broth and human urine and compared with calcium fosfomycin, pipemidic acid and cotrimoxazole. A total of 300 bacterial strains of different species from recent urinary infections were studied. Staphylococcus aureus showed the lowest MIC (0.38 micrograms/ml) and Pseudomonas spp. the highest (50 micrograms/ml) with fosfomycin salts in nutrient broth. The MIC of fosfomycin resulted in being higher than those for pipemidic acid and cotrimoxazole against Escherichia coli and Proteus rettgeri and lower for all the other species considered. The MIC values increased about ten times when urine was used as medium. No differences were observed between the two fosfomycin salts. The fosfomycin concentrations of 137-1500 micrograms/ml, easily obtained in urine of healthy adult subjects after a single dose of FOT (3g of fosfomycin), were able to kill all the strains, with the exception of Streptococcus faecalis. The bacterial adhesion of a resistant microorganism (P. aeruginosa) to the cells of the urinary tract, showed a 50% reduction after FOT treatment. PMID- 3094966 TI - Metabolism of salicylate by isolated kidney and liver mitochondria. AB - Mitochondria are known to contain a P-450 like system similar to that found in microsomes. Since previous in vivo studies from this laboratory have suggested that renal mitochondria may metabolize salicylate (SAL) to a reactive intermediate capable of protein binding, the ability of isolated kidney and liver mitochondria to activate salicylate was investigated. Renal mitochondria were 4 times more active than liver in converting SAL to a reactive intermediate and metabolized approx. 1% of the SAL to 2,3-dihydroxybenzoic acid, the catechol analogue of SAL. The formation of 2,3-dihydroxybenzoate (2,3-DHBA) and the amount of radiolabel bound to mitochondrial protein was decreased in the presence of SKF 525-A; however, excess unlabeled metabolite had no effect on binding. These data indicate that kidney mitochondria activate SAL via a cytochrome P-450 like system, but suggest that the binding species is not 2,3-DHBA itself. Oxidation of SAL and covalent binding of radiolabel, however, were also observed after the addition of ferrous iron and ascorbic acid to a model system containing [14C]SAL and bovine serum albumin. Mannitol decreased SAL oxidation and covalent binding, suggesting radical formation may represent a non-enzymatic mechanism for SAL activation. PMID- 3094967 TI - pH-dependent degradation and stabilization of meclofenoxate hydrochloride by human serum albumin. PMID- 3094968 TI - Synthesis of 3-substituted pyrazolo[1,5-a]pyridine derivatives with inhibitory activity on platelet aggregation. I. PMID- 3094969 TI - Disposition and pharmacokinetics of valproic acid in rats. PMID- 3094970 TI - [Nursing care of patients with hyperglycemic hyperosmotic non-ketotic coma]. PMID- 3094972 TI - [Isolation of viruses from rodents in Senegal (1983-1985). Description of a new poxvirus]. AB - A total of 1,397 rodents of 7 different species were collected in the major vegetative zones of Senegal. Organ pools from rodents were inoculated into suckling-mice. Thirty-five viral strains, representing 5 viruses, were isolated. The 5 viral types recovered in the present survey comprise: Bandia (23 strains), Saboya (7), Salanga (3), Gabek Forest (1) and a new poxvirus (AnD 42332) for which the name of Fadiga is proposed. This virus was isolated from a Mastomys sp collected in eastern Senegal. Antigenic relations were established by complement fixation test with Salanga virus; its distinctness was determined by neutralisation test. Our data are discussed with compiled informations on the current status of rodent viral isolations in West and Central Africa. PMID- 3094971 TI - Aromatase in breast cancer and the role of aminoglutethimide and other aromatase inhibitors. AB - Approximately one third of human breast carcinomas are hormone dependent and regress upon reduction of circulating estrogen levels. Traditional treatment strategies utilized surgical ablative methods to lower estrogen concentrations as treatment of breast cancer. Currently, investigative emphasis is focused upon development of highly specific antiestrogens and inhibitors of estrogen production. The enzyme, aromatase, as the terminal step in estrogen biosynthesis, is a logical target for blockade with potent and specific inhibitors. The earliest available aromatase antagonist, aminoglutethimide, suppresses estrogen production to the same extent as surgical ablation and is an effective treatment for breast cancer. Aminoglutethimide, however, blocks other cytochrome P-450 mediated steroid hydroxylations, requires concomitant glucocorticoid administration, and is associated with initial side effects. Several more specific inhibitors by destroying aromatase irreversibly as well as by competitive inhibition. One of these, 4-hydroxy-androstenedione, has been intensively studied in animals and is undergoing clinical trial. New data regarding these inhibitors further emphasize the key role of aromatase in estrogen production and the practical utility of blocking this enzyme. PMID- 3094973 TI - [Critical study of an interdisciplinary survey of urinary schistosomiasis in Burkina Faso]. AB - We consider an approach to built on a score summarizing some demographic, social, geographic and parasitologic data for purpose of measuring the health impact of schistosomiasis. Operational definitions are given for the social, ecological and medical variables and for the survey design. Twenty villages from the Bam Kongoussi district were kept for the survey, giving a sample of 11,396 peoples. The process of the survey is described. The overall response rate is 63%. The sensitivity of the survey's results in regard to the non-responses is considered along with the possibility to implement a call back survey. PMID- 3094974 TI - [Results of a parasitologic survey carried out in 21 villages in Konkoure Valley (French Guinea). Preliminary study]. AB - This study concern 250 children living in 21 villages. If Plasmodium falciparum, P. ovale, S. mansoni and others intestinal parasites were presents neither Dracunculus nor African filariasis have been discovered. It's probably the first study concerning this region since many years. PMID- 3094975 TI - Inhibition of 12-O-tetradecanoylphorbol-13-acetate-mediated epidermal ornithine decarboxylase induction and skin tumor promotion by new lipoxygenase inhibitors lacking protein kinase C inhibitory effects. AB - Both 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861) and 3,4,2',4'-tetrahydroxychalcone inhibited 12-lipoxygenase of mouse epidermis. The IC50 of AA861 and 3,4,2',4'-tetrahydroxychalcone for epidermal 12 lipoxygenase were 1.9 and 0.2 microM, respectively. These agents showed very weak inhibitory actions on epidermal cyclooxygenase, with the potency of inhibition for cyclooxygenase less than 1/50 of that for lipoxygenase. Induction of epidermal ornithine decarboxylase by 12-O-tetradecanoylphorbol-13-acetate (TPA; 10 nmol/mouse) was potently inhibited by these agents in a dose-dependent manner (1-30 mumol/mouse). TPA (5 nmol/mouse)-induced skin tumor formation was also strongly suppressed by these agents (15 mumol/mouse). Both AA861 and 3,4,2',4' tetrahydroxychalcone failed to inhibit partially purified epidermal protein kinase C activity. These results support the proposed involvement of lipoxygenase product(s) of arachidonic acid in TPA-induced skin tumor promotion. PMID- 3094977 TI - Comparison of two types of nonbarbiturate anesthetics during endotoxemia in dogs. AB - In dogs anesthetized with etomidate (n = 8) or droperidol-methadone-atropine (n = 5), we measured before (t = 0) and after (t = 90 min) endotoxin (1.5 mg X kg-1 IV as a bolus) systemic and pulmonary blood pressures, cardiac output and its distribution (microspheres), blood gases, blood glucose, and lactate. The effects of endotoxin depended little on the type of anesthetic. The differences between the two groups were quantitative rather than qualitative. The influence of the type of anesthesia during endotoxin shock studies should thus not be overestimated. PMID- 3094976 TI - Release of eicosanoids from white blood cells, platelets, smooth muscle cells, and endothelial cells in response to endotoxin and A23187. AB - Endotoxin produces numerous pathophysiologic changes in animals, including vascular endothelial cell damage and hematologic changes. Direct effects of endotoxin on arachidonic acid metabolism and the release of eicosanoids from endothelial cells and neutrophils have been reported. A rapid release of these autocoids occurs when cells are incubated with endotoxin, and this appears to be one of the earliest endotoxin-induced changes. Some of these eicosanoids may result in beneficial effects, and others may result in detrimental effects. This study was to determine the release of eicosanoids from white blood cells, platelets, smooth muscle cells, and endothelial cells in response to varying amounts of endotoxin and the calcium ionophore A23187. The results indicate that endotoxin has a major direct effect on vascular endothelial cells and smooth muscle cells as indicated by its ability to increase the synthesis of predominately i6-keto-PGF1 alpha by these cells. These effects were seen within a dose range of endotoxin that is lethal in horses. Very high concentrations of endotoxin (100 micrograms/ml) were required to stimulate a small increase in the production of i6-keto-PGF1 alpha and iLTC4 by freshly isolated neutrophils. Stimulation of cells with A23187 revealed that, of the eicosanoids measured, the one produced predominately by endothelial cells and smooth muscle cells was 6 keto-PGF1 alpha, by platelets was TxB2, and by neutrophils was LTC4 (LTB4 was not measured). A mixture of all white blood cells including platelets when incubated with A23187 produced large amounts of TxB2, LTB4, and LTC4 with smaller amounts of 6-keto-PGF1 alpha. The results indicate that endotoxin directly affects cells and stimulates them to produce thromboxane and prostacyclin, but very high concentrations of endotoxin were required to stimulate neutrophils to produce rather small increases in iLTC4. PMID- 3094978 TI - [Application of self-made alkaline phosphatase for ELISA in schistosomiasis japonica]. PMID- 3094979 TI - [A field investigation on the probability of the dispersion of Schistosoma japonicum eggs to Oncomelania-infested bodies of water in 4 villages of Wuxian County]. PMID- 3094980 TI - Arteriovenous carbon dioxide and pH gradients during cardiac arrest. AB - In a porcine preparation of cardiac arrest, we demonstrated that there is a marked paradox of venous acidemia and arterial alkalemia. This paradox is related to decreased clearance of CO2 from the lungs when pulmonary blood flow is critically reduced. Accordingly, increased venous PCO2 rather than metabolic acidosis due to lactic acidosis predominates during the initial 8 min of cardiopulmonary resuscitation. Arterial blood gases fail as indicators of systemic acid-base status and therefore as indicators of tissue acidosis. PMID- 3094981 TI - Influence of antioxidants (mannitol and allopurinol) on oxygen free radical generation during and after cardiopulmonary bypass. AB - Oxygen-derived free radicals (O2-, H2O2, OH.) are produced during oxidative metabolism, ischemia and reperfusion, and cardiopulmonary bypass (CPB). When oxygen free radical production exceeds scavenging capacity, peroxidation of structural lipids in cell membranes can occur with potentially injurious consequences. In this prospective study, 45 patients were evaluated to determine the effect of CPB on oxygen free radical generation. Twenty patients in group I were controls. Exogenous oxygen free radical antioxidants were administered before bypass to patients in group II (n = 15, mannitol) and group III (n = 10, allopurinol). In group I, plasma H2O2 increased during extracorporeal circulation from 65 +/- 6.0 to 125 +/- 12 microM/ml (p less than .001). At similar sampling intervals, plasma H2O2 levels were significantly lower in group II (p less than .03) and group III (p less than .05) when compared with those in group I. Red blood cell H2O2 did not change in group I or group II. White blood cell H2O2 levels decreased in group I (p less than .04) and group II during CPB. (Intracellular concentrations of H2O2 were not obtained in group III patients). We conclude that cytotoxic oxygen radicals are generated during CPB and that pretreatment with free radical antioxidants, mannitol or allopurinol, may minimize the free radicals available for lipid peroxidation of biomembranes. PMID- 3094982 TI - [The effect of the trigeminal system in facial acupuncture analgesia and its experimental morphological study]. PMID- 3094983 TI - [The effect of laser at acupoints on the coronary patient's left ventricular function and comparison with the effect of acupuncture]. PMID- 3094984 TI - [The change in left heart function by laser radiation on the zusanli point in 10 aged cases]. PMID- 3094985 TI - [The pattern and characteristics of the electrical activity of the gastrointestinal tract]. PMID- 3094986 TI - [Experimental observations on the clinical application of the electrogastrogram (EGG) and its relationship to the differentiation of traditional Chinese medicine (TCM) and acupuncture]. PMID- 3094987 TI - [Clinical observations on gastrectomy in gastroduodenal ulcer acute perforation and giant gastric ulcer under acupuncture anesthesia with a minor anesthetic]. PMID- 3094988 TI - [Neonatal neurobehavioral responses after acupuncture and general anesthesia in cesarean section]. PMID- 3094989 TI - [A study on the origin of projection of the somato-sensory area I to the central lateral nucleus]. PMID- 3094990 TI - [The segmental distribution of the afferent neurons of the "jianshi" point]. PMID- 3094991 TI - [Relationship between the pressor effect of electroacupuncture and the functions of A1, A5, and locus coeruleus nuclei]. PMID- 3094992 TI - [The comparison of the effects of electroacupuncture (EA) at the acupoints of different sides on nociceptive afferent impulses of the peripheral nerves]. PMID- 3094993 TI - [The effect of alpha-methyltyrosine on electro-acupuncture analgesia of the rat]. PMID- 3094994 TI - [The effect of electroacupuncture on falling body temperature in the rabbit and the influence of EDTA . 2Na upon it]. PMID- 3094995 TI - [Electrocardiogram effects following He-Ne laser irradiation of "neiguan" in cats]. PMID- 3094996 TI - [A preliminary report on the low impedance nature of the epidermis of the line of latent propagating sensation along the channel]. PMID- 3094997 TI - [The outline of study on the relationship between raphe nuclei and acupuncture analgesia]. PMID- 3094998 TI - [Recent advances in the relative specific connection between acupoints and the viscera and its connective pathway]. PMID- 3094999 TI - The predictive value of lipid studies in patients undergoing cardiac catheterization and open heart surgery. AB - All patients admitted for cardiac catheterization prior to possible coronary bypass surgery have a lipid profile ordered as part of their preadmission laboratory work. These studies, usually the first and only performed on the patient, include: high and low density lipoprotein-cholesterol, total cholesterol, triglyceride, and apolipoproteins A-I and B. This study was designed to determine the diagnostic significance and sensitivity of these tests based on a one-time determination as predictors of coronary artery disease. The three groups studied included those patients with surgically confirmed coronary artery disease (n = 247), aortic and/or mitral stenosis (n = 34), and normals, those free of disease (n = 30). The total population was 311 subjects, ranging in age from 20-85 years, which comprised 250 males and 61 postmenopausal females. The prevalence of the disease was 77% over the total population, with 238 of those with coronary artery disease going on to bypass surgery. Surgical results of cardiac catheterization were collected as percent occlusion. No correlations were found between lipoproteins and percent occlusion in the diseased group. Calculations of sensitivity and specificity for various lipid values suggested no clinical use for a one-time determination of these apo- and lipoproteins. PMID- 3095000 TI - Enzyme immunoassay for ceruloplasmin: application to cancer patient serum. PMID- 3095001 TI - Radioimmunoassay for nonenzymatically glycated protein in human serum. PMID- 3095002 TI - A new solid-phase assay for biotin and biocytin and its application to the study of patients with biotinidase deficiency. AB - New solid-phase assays for the determination of biotin in plasma and urine and the determination of biocytin/biotinyl peptides in urine are described. These assays were used to demonstrate that patients with biotinidase deficiency excrete increased amounts of biocytin/biotinyl peptides. PMID- 3095003 TI - Clinical significance and characteristics of creatine kinase-immunoglobulin complexes in sera from patients with malignant tumors. AB - Creatine kinase (CK, ATP: creatine N-phosphotransferase, EC 2.7.3.2) and immunoglobulin complexes were detected in 27 of 234 (11.5%) patients with malignant tumors. The complexes electrophoresed between CK-MM and the sample application point. The positive rate was significantly higher than rates in patients with benign diseases, or in healthy adults (p less than 0.001). Primary malignancies of the 27 patients were colon 8, gastric 6, pancreatic 4, liver 5, pulmonary 3 and mammary 1. As 22 of the 27 patients had a recurrence or a metastasis and the mortality rate of the positive group 6 mth after the tests was high (85%), most of the 27 patients had advanced tumors. Thus, the CK immunoglobulin complexes seem to be a prognosticator of patients with advanced tumors. The classes and types of immunoglobulins in the complexes were IgA lambda, 7; IgA kappa lambda, 5; IgA (types of the light chain were not identified), 4; IgA/G kappa, 1; IgA/G lambda, 3; and IgA/G kappa lambda, 7. The molecular sizes of the complexes were 384,000 +/- 22,000 (mean +/- 1 SD). The results of recombination assays using IgA isolated from the complexes of 4 patients suggested that the complexes in the patients' sera were mitochondrial CK IgA. Non CK-M subunit activities of the positive group were 58 +/- 40 U/l (mean +/- 1 SD) and they were significantly higher than those of the complex negative group of tumor patients (p less than 0.01). This is probably the first report of detection of mitochondrial CK-IgA complexes. PMID- 3095004 TI - The hypotensive effect of single-dose captopril in diabetics. AB - To determine the role of the kallikrein-kinin (KK) system in patients with diabetes mellitus in relation to nephropathy and/or hypertension, the single-dose effects of captopril (25 mg, p.o.) were examined in 9 control subjects and 32 diabetics (group 1; 11 normotensives without nephropathy, group 2;10 hypertensives without nephropathy, group 3; 11 hypertensives with nephropathy). Significant hypotensive effects of captopril were found in groups 1 and 2 as well as in the control group, but not in group 3. These hypotensive effects were completely blocked by the infusion of ethyl-p-(6-guanidinohexanoyloxy) benzoate methanesulfonate (FOY), a kallikrein inhibitor. The administration of captopril during vehicle infusion induced a significant elevation of plasma renin activity (PRA) at 60 and 120 min after captopril in each group, except for group 3. FOY cancelled these captopril-induced effects on PRA in those groups. No correlation was found between pretreatment PRA and the changes in mean blood pressure (MBP) after captopril during vehicle infusion in whole diabetics. In addition, the daily urinary excretion of kallikrein in group 3 was significantly lower than that in groups 1 and 2 as well as in the control group. These results suggest that the hypotensive action of captopril in diabetics without nephropathy may be largely due to activating the KK system, and that the KK system may be suppressed in hypertensive diabetics with nephropathy. PMID- 3095005 TI - Pathology of excessive production of growth hormone. AB - Since its clinical description in the last century, much progress has been made in our understanding of acromegaly. From an initial description of pituitary enlargement as just another manifestation of generalized visceromegaly, the pituitary abnormality has come to be recognized, in most instances, as the underlying aetiological factor. Gigantism and acromegaly are manifestations of disordered pituitary physiology, but the lesion responsible may be hypothalamic, adenohypophyseal or ectopic in location. The best known pathological hypothalamic basis for acromegaly is represented by a neuronal malformation or 'gangliocytoma'. It usually takes the form of an intrasellar gangliocytoma or, more rarely, a hypothalamic hamartoma. The neuronal elaboration of GHRH may play a role in the development of a growth hormone adenoma; the pituitary process may pass through an intermediate stage of somatotropic hyperplasia. When acromegaly has its basis in a pituitary abnormality, the lesion is almost exclusively an adenoma; the non-tumorous adenohypophysis shows no evidence of coexistent hyperplasia. Surprisingly, such tumours are more often engaged in the formation of multiple hormones rather than GH alone. They frequently produce not only GH and prolactin, the products characteristics of cells of the acidophil line, but also glycoprotein hormones, usually TSH. The spectrum of adenomas also varies in its degree of differentiation from a histogenetically primitive lesion, the acidophil stem cell adenoma, to well-differentiated tumours of varying cellular composition and hormone content. Each adenoma type has its clinicopathological, histochemical, immunocytological and ultrastructural characteristics. The isolation and characterization of GHRH has permitted the identification of neuroendocrine tumours, most of foregut origin, elaborating this releasing hormone. Such functional tumours induce hyperplasia of pituitary somatotrophs and may, on occasion, result in the formation of growth hormone adenomas. Resection of these GHRH-producing neoplasms results in reversal of endocrinological and sellar abnormalities. Future efforts should be directed toward the elucidation of the aetiology of pituitary adenomas, specifically whether they represent a proliferative process having its origin in endocrinological imbalance, presumably a hypothalamic abnormality, or whether it has a 'de novo' origin in the 'usual process of neoplastic transformation'. PMID- 3095006 TI - Coordinate and independent effects of heroin, cocaine, and alcohol abuse on T cell E-rosette formation and antigenic marker expression. AB - Simultaneous and independent use of cocaine and alcohol by heroin addicts was shown to variably modulate the ability of their T cells to form E-rosettes with sheep erythrocytes (E). As reported previously, the percentages of E-rosette forming T cells of both active and total types were depressed in association with heroin addiction. We show here that the kinetic curve of the rate of E-rosette formation is also depressed by heroin use and that the use of cocaine but not alcohol by heroin addicts reverses depression of E-rosette formation by heroin. The percentages of E-rosette-forming T cells from the bloods of heroin addicts who used both alcohol and cocaine, as well as the kinetic rate curves of E rosette formation, were intermediate between the essentially normal levels found for heroin addicts who used cocaine and the severely depressed levels evident for users of heroin alone or heroin plus alcohol. Modulation of the levels of E rosette formation by alcohol used in conjunction with cocaine and/or heroin was variably dose dependent. Polydrug effects evident by analyses of E-rosette formation were not seen when the percentages of lymphocytes reactive with LYT-3 (anti-E-receptor, 9.6 epitope) and OKT-3 (anti-total T cell) monoclonal antibodies were assessed cytofluorometrically, although the data suggested that subnormal percentages of LYT-3+ T cells were present when heroin addicts also used cocaine. These findings are relevant to basic understanding of T-cell physiology from a neuroimmunological perspective and also suggest ways that addictive drugs may modulate the immunocompetence of drug addicts. PMID- 3095007 TI - Multiple duodenum-jejunal diverticula in a case of scleroderma. PMID- 3095008 TI - Heterotopic ossification of the shoulder following head injury. A case report. AB - Heterotopic ossification of the shoulder following head injury is a rare occurrence. In a 26-year-old woman with a head injury and extraarticular ossification of the glenohumeral joint, the heterotopic bone was resected surgically when the mass had matured. A vigorous physical therapy program was instituted early after operation to maintain shoulder mobility. Despite the formation of adhesions, the partial reformation of heterotopic bone, and an axillary neuropraxia, the patient achieved an excellent range of active shoulder motion ten months after operation. PMID- 3095009 TI - [A case of lysinuric protein intolerance with intermittent stupor looking like psychomotor seizure in adulthood]. PMID- 3095010 TI - Nonvisualization of the liver by indium-111 oxine labeled leukocytes in alcoholic liver disease. AB - The liver was not visualized by In-111 WBC scan in a patient with alcoholic liver disease. The liver was visualized on repeat scan when liver function had improved. PMID- 3095011 TI - Transient erythroblastopenia of adolescence. AB - This case report describes a 16-year-old girl with pure red cell aplasia of 7 months duration. The erythrocyte characteristics and in vitro culture of erythroid progenitors was similar to that found in transient erythroblastopenia of childhood (TEC), a disorder most commonly seen in children 2 to 6 years of age. This case may represent the adolescent equivalent of TEC. PMID- 3095012 TI - Isolation of Neisseria gonorrhea from the urethra of asymptomatic adolescent males. AB - Symptomatic infection with Neisseria gonorrhea (NG) has become a major health problem in the adolescent population. While sexually active adults, who carry Neisseria gonorrhea may serve as a reservoir of infection even when asymptomatic, there are few data documenting the frequency of the asymptomatic carrier state in adolescent males. The purpose of this study was to determine the frequency of NG isolates in a sample of asymptomatic adolescent males (ages 13-18 years). Urethral cultures and gram stains were performed on 249 males (95% black) from a lower socioeconomic background presenting to an adolescent clinic for routine health care. Of the 249 males cultured, 177 were without symptoms or signs of urethritis. NG were isolated from four (2.26%) patients (Z = 2.03, p less than or equal to 0.043). They were also isolated from 65 (90.3%) of the remaining 72 who had either symptoms or signs of urethritis. Although 26% of the patients had documented gonococcal disease, only 8% offered a genitourinary complaint at the time of initial evaluation. Our data indicate a low but statistically significant incidence of NG colonization comparable to that found in adult males in this population of asymptomatic adolescent males. PMID- 3095013 TI - Cortical hyperostosis and enthesopathy due to long-term etretinate administration. AB - Two cases are presented which show a severe ossification disorder that we observed during long-term administration of a synthetic vitamin A analogue (etretinate). The radiologic findings are discussed in relation to the skeletal abnormalities, which occur in chronic vitamin A intoxication and retinoid hyperostosis, which has been recently described in the literature as a side effect of another retinoid (isotretinoin). PMID- 3095014 TI - Hepatic artery bolus infusion chemotherapy with mitomycin C. Angiographic results and complications. AB - Superselective catheterization of the hepatic artery and subsequent infusion of chemotherapeutic agents is an accepted treatment of inoperable hepatic neoplasms. In this article the results of 85 hepatic arterial infusions in 37 patients with biopsy-proven malignancies of the liver, treated in a period of 4 years, are described. Treatment consisted of a bolus injection of mitomycin C for a 10-min period. In 9 catheterizations (10.6%) a dissection of the hepatic artery occurred, followed by occlusion in 5 cases (5.8%). Gastric ulcers were seen in 2 patients, without evidence of displacement of the catheter. In 1 patient the catheter did displace leading to toxic gastritis, and subsequent pulmonary complications led to the patient's death. The response rate appeared to be 42% for colorectal cancer and 70% for breast cancer. The median duration of the response in colorectal cancer and breast cancer was 4 and 10 months, respectively. PMID- 3095015 TI - The effects of posture on the metabolic and ventilatory response to low level steady state exercise. AB - Low level exercise is frequently used to assess cardiac and pulmonary function. This study examines the differences in both metabolic and respiratory patterns between the sitting and supine position. Six normal male subjects were studied in both positions during four levels of exercise (12.5, 25, 37.5 and 50 W). Oxygen consumption (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were greater when sitting as were the ventilatory equivalents to O2 (VE/VO2) and CO2 (VE/VCO2). Respiration was compared at equivalent workloads; the greater minute ventilation observed during sitting was due to greater tidal volumes (VT) and mean inspiratory flows (VT/TI). Expiratory time (TE) was longer and inspiratory duration shorter under most conditions when sitting. When breathing patterns were compared at similar degrees of minute ventilation, VT, TE and VT/TI were greater when sitting, while respiratory frequency (fR) was slower. PMID- 3095016 TI - Respiratory gases. AB - Respiratory gases have access to the human circulation by diffusing through alveolar walls into pulmonary capillaries. Because of this circulatory access, these gases can act like other types of drugs, and can produce effects both locally in the lungs and systemically in distant organs or tissues. This article reviews the metabolism, pharmacology, and therapeutic use of the three most common gases used in the practice of respiratory medicine: oxygen, carbon dioxide, and helium. PMID- 3095017 TI - The application of health economics to health promotion. PMID- 3095018 TI - Occurrence and aeruginocine typing of Pseudomonas aeruginosa in buffaloes and their environment. AB - The occurrence and distribution of Pseudomonas aeruginosa in buffaloes and their environment was studied. Environmental sources included milkers, milking utensils, watering troughs, animal shed floor, barn-yard soil and drains. Of the different body sites examined, the organism could only be isolated from 15% of the muzzle and 5% of the belly samples. The organism was widely prevalent in the animal environment and could be isolated from milking utensils (56.67%), watering troughs (44.00%), drains (36.37%), shed floor (4.00%), barnyard soil (3.33%), and milkers' throats (50.00%) and hands before and after milking (7.14 and 10.71%, respectively). Aeruginocine typing revealed that of the 68 strains of P. aeruginosa, 65 (95.59%) were typable. Amongst the typable strains, 21 (32.30%) were classifiable and 44 (67.69%) unclassifiable. Unclassifiable pattern 23478- was most predominant and common to animals and environmental sources. Different aeruginocine types encountered were: A(2), B(4), F(1), L(1), P(4), 1(1), 8(1), 9(1), 11(3), 12(1), 14(1) and 17(1). This is of significance as most of the types encountered have been reported from clinical specimens of animal and human origin. PMID- 3095019 TI - Further evidence for the heterogeneity of serum albumin. AB - Albumin samples from three species (avian, bovine and human) were electrophoresed on gradient polyacrylamide gels in the presence of sodium dodecyl sulphate (SDS PAGE). The resulting electrophoregram from each sample of serum albumin investigated showed multiple protein bands of a wide range of molecular weights. All seven samples of human serum albumin were found, using gel immunodiffusion, to be contaminated with other proteins. All but one sample was contaminated with proteins such as haptoglobin, alpha 1-glycoprotein, alpha 1-trypsin inhibitor, and prealbumin. This contamination accounts for part of the heterogeneity of these samples. Immunoblots, where the proteins were transferred to nitrocellulose and incubated with antisera, gave a better demonstration of the heterogeneity than Coomassie Blue staining and the immunoblotting procedure appeared to be more sensitive than the gel immunodiffusion technique. The heterogeneity of serum albumin demonstrated by the former technique included that of the monomer which was shown to be contaminated with antithrombin III. The commercial samples of human serum albumin, claimed as pure, were found to vary greatly in their tryptophan content, which also indicated heterogeneity. Heat treatment of human serum albumin with 1% SDS, followed by chromatography on agarose, removed the protein contaminants and with it the tryptophan. The presence of tryptophan in human serum albumin, therefore, indicated the presence of impurities. PMID- 3095020 TI - Adaptation of Drosophila enzymes to temperature--V. Heat shock effect on the malate dehydrogenase of Drosophila melanogaster. AB - Drosophila melanogaster cMdh allozymic variants (MdhF MdhF/S, MdhS) were subjected to heat shock (33 degrees C/30 min----40 degrees C/30 min). This stress increases differentially MDH specific activity, with the cMdhF strain showing greater response as compared with the cMdhS one; heterozygotes exhibited generally intermediate values. Correlative differences were also revealed for some catalytic properties (Vmax, Vmax/Km ratio, thermostability) of the cMDH; this is not true for the mMDH. The catalytic behavior of the enzyme is correlated with the differential survival of the cMdh variants, with the cMdhF showing again higher survival than the cMdhS one, a fact which seems to contribute to temperature adaptation of D. melanogaster. PMID- 3095021 TI - Isolation and molecular weight determination of two immunoglobulin heavy chains in the channel catfish, Ictalurus punctatus. AB - Channel catfish (Ictalurus punctatus), a teleost fish, were immunized over a 4 month period with 4 intraperitoneal injections of bovine serum albumin (BSA) in Freund's adjuvant. The catfish anti-BSA antibody was purified by affinity chromatography and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). By elution of catfish anti-BSA antibody from BSA affinity columns with 3.0 M KSCN and subsequent SDS-PAGE, two immunoglobulin heavy chains were demonstrated in the channel catfish. The molecular weights and the relative percentages found of the two immunoglobulin heavy chains were 72,000 (94%) and 56,000 (6%). The molecular weight of the single light chain found was 23,000. Using the 72,000 mol. wt heavy chain and 23,000 mol. wt light chain and including a molecular weight of 15,000 for the J-chain, the molecular weight of the predominant channel catfish tetrameric IgM immunoglobulin molecule was calculated to be 775,000. Using the 56,000 low mol. wt heavy chain, the molecular weight of a second subclass of the channel catfish tetrameric IgM molecule was calculated to be 647,000. After Sephadex G-200 gel filtration, anti-BSA antibody activity was found only in the 14S globulin fraction by indirect hemagglutination testing. PMID- 3095022 TI - Activation of the alternative pathway of complement by DL-2-mercaptomethyl-3 guanidinoethylthiopropanoic acid (Mergetpa). AB - Incubation of normal human serum with 3-5 mM Mergetpa causes activation of the alternative pathway of complement as indicated by fragmentation of C3 and factor B, dependent on the presence of divalent cations. Mergetpa inhibits the regulatory protein factor I and, as a consequence, may allow initiation of the feedback cycle of the alternative pathway by deregulation. The classical pathway is not or only to a minor extent activated. A decrease in the hemolytic activity of C2, C5 and one or several of the components C6-9 in the presence of 5 mM Mergetpa may be explained by direct inactivation. The described effects are probably mediated by Mergetpa acting as a thiol. PMID- 3095023 TI - Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment. AB - The contraceptive efficacy of progestin-only contraception was studied in epileptic patients using NORPLANT subdermal capsules. The effect of anticonvulsants on levonorgestrel plasma levels was determined. NORPLANT subdermal capsules were inserted into nine epileptic women, and ten control women using no medication. Venous blood samples were taken at 0, 1, 3, 6, 9 and 12 months after insertion and the concentration of levonorgestrel was determined by radioimmunoassay. At 3 to 12 months, the overall mean concentration of plasma levonorgestrel was significantly lower in the six epileptics taking phenytoin alone or in combination with other anticonvulsants (203 +/- 128 pg/ml, mean +/- SD) than in the controls (325 +/- 135 pg/ml, p less than 0.01). After one year, nine of the control patients continued the use of NORPLANT and no pregnancies occurred. Two of the nine epileptics became pregnant during contraception by NORPLANT. They both used phenytoin and their plasma concentrations of levonorgestrel were low near the time of conception. Levonorgestrel released from the capsules had no apparent harmful effects on epilepsy and none of the patients reported an increase in seizure frequency. The results show that contraception by the progestin levonorgestrel is not reliable in epileptic patients using anticonvulsants known to induce metabolizing enzymes of the liver. PMID- 3095024 TI - Uterine arginase inhibition affect the rat embryonic development. AB - The presence of polyamines (putrescine, spermidine and spermine) and the enzymatic activity of extrahepatic arginase (E.C. 3.5.3.1) which catalizes the hydrolysis of L-arginine into L-ornithine and urea have been related with cellular growth and development in several tissues. The enzymatic activity of arginase in rat implantation sites and its participation in reproductive process is demonstrated. Long-Evans adult rats during the 4th or 5th days of pregnancy were utilized. Arginase activity is higher in non-decidualized tissue (86.1 +/- 33 nmoles of urea/mg protein/min-1) when was compared with implantation sites (61.7 +/- 17). Intrauterine administration of several concentrations of a new synthetic L-ornithine analogue, AIAVA (2-amine-5-iodoacetamide valeric acid), produced embryonic growth arrest concomitant with arginase inhibition but not ornithine decarboxylase. From our results it is possible to stress the metabolic importance of uterine arginase in reproductive process. PMID- 3095025 TI - Evaluation of noninvasive measurements of oxygenation in stable infants. AB - The accuracy with which transcutaneous measurements of oxygen tension reflect PaO2 in older infants has recently been questioned. We therefore examined the effect of maturation, i.e., age or skinfold thickness, on the accuracy of transcutaneous oxygen tension (PtcO2) and oxygen saturation (StcO2) measurements in 19 infants (age 1 to 61 wk) undergoing elective cardiac catheterization. Twenty-seven simultaneous arterial and transcutaneous measurements revealed a good correlation between PtcO2 and PaO2 (r = .91, slope .77, intercept 3.23 torr). The mean arterial-transcutaneous PO2 difference of 10 torr (range - 15 to 35) was independent of age but was significantly correlated with skinfold thickness (r = .45, p less than .05). There was also a good correlation between StcO2 and SaO2 (r = .95, slope .65, intercept 27.8%). The mean arterial transcutaneous oxygen saturation of 1.4% (range - 17.3 to 14) was unaffected by age or skinfold thickness. However, neither PtcO2 or StcO2 measurements were accurate in patients with severe hypoxemia; StcO2 consistently overestimated the SaO2 when the SaO2 was below 70%. Thus, in this study the discrepant PtcO2 measurements in older infants were due to increasing skinfold thickness rather than age. PtcO2 monitoring still has an important role in oxygen monitoring and together with StcO2 provides valuable information on oxygenation. PMID- 3095026 TI - Calculation versus measurement of total energy expenditure. AB - In acutely ill patients both hypo- and hyperalimentation must be avoided by adjusting caloric intake to total energy expenditure (TEE). We determined the discrepancy between basal energy expenditure (BEE) calculated from the basic Harris-Benedict formula and TEE measured by continuous indirect calorimetry in a heterogeneous group of mechanically ventilated surgical patients. We also compared the accuracy of TEE calculated from the corrected Harris-Benedict formula or estimated by intermittent indirect calorimetry to that of TEE measured by continuous indirect calorimetry. The poor correlation between calculated BEE and measured TEE was significantly (p less than .05) improved by a correction factor based on each patient's clinical condition. The mean absolute difference between calculated TEE and measured TEE was 8.9 +/- 9.6 (SD) %. Calculations were significantly (p less than .05) improved by estimating TEE from two 5-min recording periods, which suggests that continuous indirect calorimetry may not always be necessary to guide caloric replacement. PMID- 3095027 TI - Major airway obstruction relieved by helium/oxygen breathing. PMID- 3095028 TI - Ordering concentrated hyperalimentation solutions for critical care. PMID- 3095029 TI - Transformation in cyanobacteria. AB - The lack of any known transduction or indigenous conjugation systems has left transformation as the major means for genetic manipulations in cyanobacteria. Studies of transformation in cyanobacteria generally have dealt with one of two distinct areas. The first area is genomic transformation where internalized donor DNA recombines with chromosomally located genes. Chromosomal transformation can be a powerful tool for genetic mapping and mutagenesis. The second area is plasmid transformation where internalized plasmid donor DNA becomes established as an independent replicon in the recipient cyanobacterium. This second area has received a great deal of attention because it allows the generation of merodiploids for studies of genetic regulation and control and because it potentially allows the expression of foreign genes in an oxygenic photoautotroph. This article will attempt to describe the development of our current understanding of these two types of genetic transformation in cyanobacteria. PMID- 3095030 TI - Pheromones among the procaryotes. AB - A pheromone is a chemical excreted by an organism into the environment that acts to elicit a specific response from other organisms of the same species. The importance of pheromones in the life cycle of various species of mammals, insects, and fungi is well known. In the past decade, it has become apparent that pheromones influence the behavior and development of prokaryotes. Pheromones excreted by myxobacteria, actinomycetes, and cyanobacteria elicit specific developmental responses from these organisms. In addition, pheromones excreted by Streptococcus faecalis function in conjugation, and pheromones of luminescent bacteria regulate bioluminescence of these organisms. PMID- 3095031 TI - Immunological comparison of heat-shock proteins and alpha-crystallin. AB - It has been shown using ELISA and affinity chromatography, that extracts from heat-shocked Drosophila melanogaster larvae and cultured cells react with monoclonal antibodies raised against bovine alpha-crystallin. It is suggested that this cross-reactivity is associated with the region of the sequence corresponding to residues 98-108 of the bovine alpha A-crystallin chain. This region may be important for the functions of both alpha-crystallin and the heat shock proteins. PMID- 3095032 TI - Clinical aspects of exercise and diabetes mellitus. PMID- 3095033 TI - Interrelations of exercise and diet on bone metabolism and osteoporosis. PMID- 3095034 TI - Gastrostomies: evolution, techniques, indications, and complications. PMID- 3095035 TI - Cellular metabolism in sepsis: effects of nutritional therapy. PMID- 3095036 TI - Monitoring oxygen therapy. Is it worth the cost? PMID- 3095037 TI - Home care for life-supported persons. Is a national approach the answer? AB - In France, home care services for ventilator-assisted persons are provided by 28 not-for-profit regional associations. National issues are resolved by an organization (ANTADIR) which is a federation of these associations. Each component of the system has defined, specific roles and responsibilities. This cost-saving approach has made life possible in the community for over 1,200 ventilator-assisted people. Realities in other nations may demand that a system be put in place to meet the needs of this patient population and those involved in serving them. Although differences exist between countries, there is value in scrutinizing what is already in place in France to help determine what can be developed in other nations. PMID- 3095038 TI - Tuberculosis long-term care beds. Have we thrown out the baby with the bathwater? PMID- 3095039 TI - Baby needs a new pair of shoes. PMID- 3095040 TI - Management of asthma. A Canadian perspective. PMID- 3095041 TI - Serum cholesterol in China and the West. PMID- 3095042 TI - Free medial thigh flap in treatment of advanced burn cases. PMID- 3095043 TI - Subtotal splenectomy in cirrhotic patients. PMID- 3095045 TI - Polarized and scanning electron microscopy of urinary calculus structure. PMID- 3095044 TI - Recognition and management of juxtarenal aortic occlusion. PMID- 3095046 TI - Ultrastructural investigation of experimental non-union of fractures. A transmission electron microscopic study. PMID- 3095047 TI - Crossed nigrostriatal dopaminergic pathway. PMID- 3095048 TI - Tumoral calcinosis. A case report. PMID- 3095049 TI - Quantitative template-quick Kato's smear for helminthic egg count. PMID- 3095050 TI - Combined bilateral free latissimus dorsi skin flap transplantation. Report of a case. PMID- 3095051 TI - A preliminary study of serum interferon in systemic lupus erythematosus and its significance. PMID- 3095052 TI - Depressant effects of anesthetics on isolated human gravid and non-gravid uterine muscle. PMID- 3095054 TI - Acupuncture induced phantom limb and meridian phenomenon in acquired and congenital amputees. A suggestion of the use of acupuncture as a method for investigation of phantom limb. PMID- 3095053 TI - Intra-arterial cisplatin chemotherapy with surgery and/or radiotherapy in advanced cervical and vaginal carcinoma. PMID- 3095056 TI - Malignant ganglioneuroma of adrenals with metastasis to liver and spleen. PMID- 3095057 TI - Variegated expression of the Sgs-4 locus in Drosophila melanogaster. AB - Experiments on T(1;4)wm258-21 larvae of Drosophila melanogaster are described which establish the existence of a salivary gland specific marker for position effect variegation. The marker is a glue protein gene called Sgs-4 which is expressed during the third larval instar. Using temperature as a variegation modifier, we showed that cytological compaction for the Sgs-4 chromosomal locus is enhanced at 17 degrees C and reduced at 29 degrees C. We also found that the Sgs-4 protein and transcript from salivary glands at 17 degrees C accumulate to roughly half the levels found in salivary glands at 29 degrees C. Southern analysis suggested that the Sgs-4 locus at 17 degrees C is polytenized to roughly one-third the level at 29 degrees C. The results are discussed with respect to alternative models of variegation. PMID- 3095055 TI - Fibrous band compression at the elbow as a cause of ulnar neuritis. PMID- 3095059 TI - [Determination of N-Dipropylacetamide serum concentration and its clinical significance in epileptic children]. PMID- 3095058 TI - [Single antiepileptics versus combined antiepileptics in the treatment of epilepsy]. PMID- 3095060 TI - [Clinical significance of serum concentration of carbamazepine orally administered to epileptic patients]. PMID- 3095061 TI - [Determination of blood carbamazepine and its application in antiepileptic treatment]. PMID- 3095062 TI - [Immunoglobulins in the CSF and serum and immunologic mechanisms in 71 patients with general tonoclonic epileptic seizures]. PMID- 3095063 TI - [Relation between serum IgA and HLA in patients with epilepsy]. PMID- 3095064 TI - [Pedigree study on seven families with a high incidence of epilepsy]. PMID- 3095065 TI - [Pedigree EEG study on inheritance factors in epilepsy]. PMID- 3095066 TI - [An epidemiology study on acute sporadic viral hepatitis in Taiyuan]. PMID- 3095067 TI - [Mycoflora in naturally fermented Chinese sauces in Beijing and their assay for aflatoxin B1]. PMID- 3095068 TI - [A waterborne outbreak of non-A, non-B hepatitis epidemic]. PMID- 3095069 TI - Occurrence of adenocarcinoma in the colon sigmoideum following Maydl's operation for urinary bladder exstrophy. AB - Two cases of colonic adenocarcinoma appearing 44 and 25 years, respectively, following an operation for urinary bladder exstrophy done according to Maydl are reported. A need for regular controls of patients with inner urine derivations has been emphasized. In the case of a suspected tumour it is necessary to alter the inner derivation to an outer one and also a resection of the colon at the site of the urinary bladder trigone is required. The Czech surgeon Karel Maydl was the first to implant the trigone of a splitted urinary bladder into the colon sigmoideum in 1892. This type of operation is used even today by several European urologists with excellent long-term results with respect to the preservation of an intact ureterovasical passage which prevents the reflux of the intestinal contents into the ureter, and also prevents the formation of strictures in the terminal parts of the ureter. In two patients who had been living for 25 and 44 years since they were operated on for urinary bladder exstrophy according to Maydl, a colonic adenocarcinoma was diagnosed. The tumour directly affected the implanted trigone wall and also involved the surrounding parts of the colon wall. PMID- 3095070 TI - Formation of calcium oxalate urolithiasis in experiment and its inhibition by pyridoxine and magnesium. AB - Possibility of application of experimental model of calcium oxalate urolithiasis to the study of some medicament actions useful in prevention of calcium oxalate urolithiasis in men has been examined in animal experiments. Inhibition effects of pyridoxine and magnesium in formation of calcium oxalate stone formation have been proved. Administration of pyridoxine and/or magnesium to experimental animals inhibited formation of incrustations on renal papillae. Administration of nothing but magnesium lowered considerably also frequency of nephrocalcinosis occurrence. Good reproducibility of applied model of calcium oxalate urolithiasis creates conditions for further experimental study of this kind of urolithiasis. In the previous series of experiments (4) we tiped out an experimental model of calcium oxalate urolithiasis in animals well reproducible in our conditions. In the following period we were interested, whether the created model can be applied to verification of efficiency and further study of some medicaments affecting this kind of urolithiasis. At present, pyridoxine and magnesium are mode widely used for prevention of calcium oxalate urolithiasis in the clinical practice. Therefore, we decided to use the possibilities of the evaluated experimental model for the study of their inhibition effects. The results of experiments are presented in this paper. PMID- 3095071 TI - On the mechanism of acute toxicity of phosmet. AB - Rats were given single oral doses of phosmet (LD50 or 3/4 LD50). Changes of hematological parameters were studied in several time intervals; the main interest was paid to disturbances in blood clotting. Both light and electron microscopy were used to evaluate histopathological changes in selected organs (liver, lungs, spleen, stomach). Marked changes could be observed in all blood clotting parameters studied, other findings were not standard. The pathological picture was dominated by endothelial damage to the blood vessels and findings of thrombocytic clots in microcirculation of all organs examined. Together with hemocoagulation changes, they could be considered as reflecting the compensated stage of diffuse intravascular coagulopathy. In addition, damaged alveolar endothelium and interstitial edema could be observed in the lungs together with hepatic steatosis, damaged proximal renal tubuli, release of cellular elements from the splenic pulp and decomposition of megakaryocytes as well as serious exfoliation of the superficial layers of the gastric mucosa. The pathohistological alterations coincided with changes in organ weights. PMID- 3095072 TI - Transferable resistance to cephalosporins, ureidopenicillins and trimethoprim. AB - Transferable resistance to classical Cephalosporins emerged three years ago among Enterobacteriaceae simultaneously in several hospitals and was associated with resistance to other betalactam drugs, i.e. with a transmissible TEM-like betalactamase. A systematic survey of incidence of R plasmids in Proteus sp. lead, in two district PHLs, to demonstration of transferable Azlocillin resistance. This resistance was most frequently associated with that for Carbenicillin, but also strains susceptible to CAR but resistant to AZL have been isolated. Trimethoprim resistance was in this country first described by Schon, but, since then, it is now frequently found transferable in polyresistant strains from hospitals, resistant also to betalactam antibiotics, Gentamicin and other drugs. PMID- 3095073 TI - Comparison of effectiveness of aminoglycosides and cephalosporins in gram negative rods. AB - Aminoglycosides and cephalosporins belong among antimicrobials with a pronounced effect on most gram-negative rods. In vitro susceptibility and resistance to gentamicin, tobramycin, amikacin, netilmicin, cefoxitin, cefotaxime, cefsulodin, cefoperazone in Klebsiella pneumoniae, Enterobacter spp., Proteus mirabilis, Escherichia coli and Pseudomonas aeruginosa was tested by the quantitative dilution micromethod. Selected, highly susceptible strains of the above species were furthermore compared for minimal inhibitory concentration (MBC) and minimal bactericidal concentration (MBC) values. Aminoglycosides tended to be the most effective drugs for susceptible strains. In view of their relative toxicity possibly optimal combinations of individual aminoglycosides with individual cephalosporins are discussed. PMID- 3095074 TI - Changes of pharmacokinetic in rats after bilateral nephrectomy--a model for prediction of pharmacokinetic changes in patients with chronic renal insufficiency. AB - Elimination of gentamicin, tobramycin, amikacin, cefoperazone, ceftriaxon and lithium was investigated in healthy and bilaterally nephrectomized rats. This model of renal failure was used to determine the nonrenal elimination constantsebz, diesambino calculation of the ratio of the nonrenal and total elimination constant Qo. The values of Qo of the investigated drugs in the used model were very close to those given in the literature for men. These results suggest that the described model can be helpful in predicting the percentage of drug excreted renally and nonrenally, and the delay in drug excretion in renal insufficiency. PMID- 3095075 TI - The influence of furosemide on intrarenal distribution of 2-sulphanilamido-5 methoxypyrimidine in rats with normal and reduced renal parenchyma. AB - Internal distribution of 2-sulphanilamido-5-methoxypyrimidine (SM) 100 mg/kg in rats is characterized by a corticopapillary gradient. The papilla/cortex ratio of SM concentration averaged 2.25 +/- 0.34. Furosemide (5 mg/kg) elicited a significant corticopapillary gradient decrease for SM. Corticopapillary gradients for SM and sodium showed a positive correlation (r = 0.45; p less than 0.001). After furosemide corticopapillary gradient for SM averaged 1.4 +/- 0.22. Unilateral nephrectomy alone induced no significant difference in the corticopapillary gradient for SM compared with controls. Corticopapillary gradient for SM was significantly lower in unilaterally nephrectomized rats than in controls when furosemide was given after 24 hours or 7 or 14 days. The results suggest that SM concentration was significantly higher in the medulla than in the cortex; furosemide led to a significant decrease of corticopapillary gradient for SM against controls; the corticopapillary gradient for SM did not significantly change after unilateral nephrectomy; the effect of furosemide on corticopapillary gradient for SM was more pronounced in rats after unilateral nephrectomy than in controls. PMID- 3095076 TI - Pharmacokinetics of cefoperazone in healthy volunteers. AB - Pharmacokinetics of cefoperazone was studied in 10 healthy volunteers following 15 min intravenous infusion of 2 g. Cefoperazone levels in the blood serum and in the urine were determined microbiologically. At the end of the infusion, mean serum concentrations of the antibiotic were 340.4 (+/- 81.5) mg/l, at the 4th hour after the infusion 38.4 (+/- 10.3) mg/l, and 12 hours after the infusion all subjects had detectable concentrations with the mean value 2.2 (+/- 0.7) mg/l. Within 12 hours, 33.3 (+/- 6.1) % of the total dose of cefoperazone had been eliminated in the urine. The fitting of the individual serum concentration curves and the determination of pharmacokinetic constants were done according to a two compartment model with the aid of nonlinear least-squares regression analysis on a programmable calculator TI 59. The mean value of the biological half-life (beta phase) of cefoperazone was 1.77 (+/- 0.25) h, mean serum clearance was 61.7 (+/- 12.1) ml/min and the mean distribution volume (Vd area) was 9.44 (+/- 2.2) 1. Our data are in agreement with those previously reported in the literature. The only exception is the distribution volume, which we found to be smaller. PMID- 3095077 TI - Pharmacokinetics of azlocillin after intramuscular application. AB - The first pharmacokinetic data are reported of azlocillin injected intramuscularly to adult probands. The blood serum and urinary levels of azlocillin were determined microbiologically in 8 healthy volunteers after intramuscular injection of 2 grams. Peak serum levels of azlocillin were found by the end of hour 1 after injection, average level was (55.06 +/- 10.25) mg/l. At hour 2 the average level was (33.64 +/- 6.46) mg/l. and at hour 4, (9.47 +/- 1.79) mg/l. The biological half-life was 1.4 hour. In urine, (41.2 +/- 7.7)% of the administered dose was eliminated within 8 hours on average. PMID- 3095079 TI - Short-term prophylaxis in cardiovascular surgery. PMID- 3095078 TI - Ceftriaxon in the treatment of severe bacterial infections. AB - The efficacy of ceftriaxon (Rocephin Roche) therapy has been studied by our team in two groups of patients. The first one consisted of 10 children suffering from a diffuse purulent appendical peritonitis brought about by a mixed aerobe and anaerobe microbial flora, the second one comprising 7 patients with severe infections caused by problematic aerobe pathogens. The clinical effect of the treatment was good in 16 out of the 17 cases, in one patient it could not be evaluated. Even though a high degree of sensitivity to Rocephin could be demonstrated bacteriologically by the disc method in all the aerobe germs present, the results of titration of the bactericide capacity of the sera during treatment indicate the need for laboratory monitoring of the course of therapy of severe infections due to pseudomonas aeruginosa. Parenteral administration of Rocephin was well tolerated and the laboratory alterations seemin the course of therapy of severe infections due to Pseudomonas aeruginosa. Parenteral administration of Recephin was well tolerated and the laboratory alterations seen in the postoperative ileus due to strangulation and adhesions--cannot be recommended. PMID- 3095080 TI - Comparison of oral lavage methods for preoperative colonic cleansing. AB - Polyethylene glycol electrolyte lavage solution was compared with a 10 percent mannitol solution for preoperative colonic cleansing. Eighty patients were prepared randomly with one of these solutions on the afternoon prior to surgery. Colonic cleansing was better with polyethylene glycol electrolyte lavage (90 percent optimal cleansing vs. 75 percent). Analysis of hematologic, biochemical, and weight changes before and after the bowel preparation, demonstrated a mild subclinical dehydration with the use of mannitol. Evaluation of patient tolerance demonstrated more nausea, cramps, and abdominal pain with mannitol. Other symptoms were similar with both preparations. Colonic hydrogen gas was sampled during surgery, and two patients in the mannitol group had combustible levels. This study confirms that both 10 percent mannitol and polyethylene glycol electrolyte lavage are safe, effective methods of preoperative bowel cleansing. Better cleansing, patient tolerance, and lower hydrogen gas level make polyethylene glycol electrolyte lavage the preferred method. PMID- 3095081 TI - Assessing value of diabetes patient education. PMID- 3095082 TI - Safety evaluation of ritanserin--an investigational serotonin antagonist. AB - Ritanserin is an investigational serotonin-S2 receptor antagonist with activity in a variety of psychiatric disturbances characterized by dysthymia or anxiety. This investigation evaluates acute safety and tolerability of ritanserin in 12 healthy males. Ritanserin 10 mg, 20 mg, and placebo were administered as single doses in a randomized, double-blind, crossover fashion. Treatment effects on vital signs, laboratory tests, a mood evaluation test, electrocardiograms (ECGs), and reported adverse experiences were monitored. Plasma levels were determined at two hours postdose. Results indicated no clinically relevant effects on vital signs, laboratory tests, ECGs, or mood evaluations. Dose proportionality was demonstrated. The incidence of total adverse effects (primarily somnolence and fatigue) after single-dose administration was 25 percent for placebo, 75 percent for 10 mg, and 81.8 percent for 20 mg. There was a relationship between incidence of adverse effects and dose, but no general correlation between plasma levels and severity of adverse experiences. The results indicate that ritanserin is safe and tolerable following acute administration of 10 mg and 20 mg oral doses. PMID- 3095083 TI - [Lung parenchyma disease following instillation of mitomycin C in the bladder]. AB - After instillation of mitomycin C into the urinary bladder severe pulmonary changes developed in a 35-year-old man. This complication has previously been described only after systemic administration of the drug. If mitomycin C is administered locally the lungs should be regularly examined. PMID- 3095084 TI - Early expression of carbonic anhydrase II (CAII) in transitory glial cells of the developing murine nervous system. AB - Using immunocytochemical methods carbonic anhydrase II (CAII) has been detected in the embryonic mouse central nervous system as early as in stage E16. In the spinal cord and the brain stem, the enzyme first appeared in transitory cells probably derived from the radial glia. In the cerebrum such transitory cells were never stained with anti-CAII sera. The bodies of CAII-positive cells were never visualized in the ventricular layer. The controversial cellular specificity of CAII made it impossible to specify the glial lineage to which these transitory CAII-positive cells are committed. PMID- 3095085 TI - [Prevention of genetic eye diseases]. PMID- 3095086 TI - [Dynamic EEG mapping--an imaging procedure for studying perceptive, motor and cognitive brain performance]. AB - The spatial pattern and time course of cortical activation can be studied when the event-related desynchronization in 30 EEG recordings is being quantified, averaged over about 60 events and displayed in form of maps with integration times of 125 ms (8 maps/s). This method was named dynamic mapping and used for investigating cortical activation pattern during the following tasks: Planning and execution of voluntary self-paced thumb movements, tactile stimulation of the foot sole and recognition of words, displayed shortly on a computer terminal. All these experiments resulted in localized activation pattern. PMID- 3095087 TI - [Validity of early acoustically-evoked potentials in the diagnosis of brain death]. AB - Brainstem acoustic evoked potentials (BAEP) in clinically proven brain death are already described in the literature. In most cases there were no reproducable BAEP or only wave I ipsilateral. In a few cases, shortly after the onset of brain death, wave I and a wave II ipsilateral have been detected. 40 Patients were examined during developing brain death and in brain death. Using an ipsilateral and contralateral montage (mastoid/vertex) four different patterns of BAEP in brain death could be distinguished: Wave I ipsilateral and wave II ipsilateral, reduced in amplitude and delayed in latency and a wave I-contralateral, Wave I ipsilateral and wave I-contralateral, Only wave I ipsilateral, No reproducable BAEP. In clinically not brain dead patients, three different patterns of BAEP are recorded which should be known in order to comment on the validity of the method in the diagnosis of brain death: Only wave I and a flat and late wave, only recordable using several reproductions and with a low rate of artefacts. Only wave I recordable while the patient is still breathing spontaneously (false positive results). Reversible loss of wave I. Ignoring the results, the BAEP may lead to false positive results in the diagnosis of brain death. PMID- 3095088 TI - [Interactive microcomputer program for calculation and normal values for routine clinical neurophysiological research]. AB - A BASIC program for a 128 KByte microcomputer is described which is deviced to support every day clinical neurophysiological investigations. It provides calculating routines and normal values with a hard copy print option for visual, auditory, and somatosensory evoked potentials, peripheral motor and sensory nerve conduction velocities, and needle EMG potential analysis. All important arm and leg nerves and muscles are included. By its simplicity the program gives easy access to changes according to individual requirements. PMID- 3095089 TI - [Disorders of motor unit discharge activity in parkinsonism]. AB - The discharge activity of single motor units (MUs) of the first dorsal interosseus muscle was recorded in slight stationary isometric contractions. Normal subjects and patients with parkinsonism of various degrees were investigated. The purpose was to study disturbances of the discharge pattern in the patients and their potential diagnostic role. Automatic signal recognition and statistical analysis of the interval distribution were used. Most MUs of the patients revealed considerable irregularities of their discharge sequences best marked by the so called "floating standard deviation". All patients, also 2 without tremor, showed a characteristic synchronization of their MU discharges ("broad-peak" type). Since the above changes were also seen in the patients with only slight symptoms, these investigations, if methodically simplified, could be of diagnostic value. PMID- 3095090 TI - [Dependence of the action potential amplitude of motor units on the recruitment threshold: implications for electromyography]. AB - The relationship between the action potential amplitude and the threshold force of recruitment of 275 motor units (MU) recorded from the first dorsal interosseus muscle of 15 healthy subjects was analysed. The number of newly recruited MU decreased exponentially with increasing muscular force. Action potential amplitudes showed a highly significant positive linear correlation with threshold force of recruitment. This relationship is in accordance with the size principle of MU recruitment. Applying the rank correlation method, 88.6 +/- 2.0% (mean +/- standard deviation) of paired comparisons between all MU of one subject followed the normal activation sequence of MU with an increasing action potential amplitude. It is shown that small variations of the distance between the leading off surface of the electrode and the MU recorded do not affect these findings. These results demonstrate that the force at which a MU is recruited is the most important factor influencing MU action potential amplitude in normal subjects. So far this fact has not been adequately appreciated in clinical electromyography although it is of significance for the assessment of pathological conditions. PMID- 3095091 TI - [The bulbocavernosus reflex in controls and patients with potency disorders]. AB - The bulbocavernosusreflex (BCR) was examined in 34 controls and in 98 patients with disturbances of potency. The shortest and longest latencies, the mean and the temporal dispersion out of ten successive reflex responses were measured. Additionally the smallest and largest side differences were determined when recording reflex responses simultaneously from the right and left bulbocavernosus muscles. BCR measurements revealed pathological results in 57 patients. Most sensitive parameters were the temporal dispersion and maximum side difference. PMID- 3095092 TI - [EEG in migraine]. AB - The character and extent of EEG-changes in 40 patients with migraine accompagnee and 41 patients with classical migraine were studied and the EEG-diagnoses of both groups were compared. Moreover, the EEG-diagnoses in these patients were compared in relation to a control-group. The EEG showed pathological findings in 10 patients (83%) during the attacks and in 39 patients (57%) during the intervals with predominating focal changes (51%). Patients with migraine accompagnee had more frequently pathological findings (70%) as well as focal changes (60%) than patients with classical migraine (51% respectively 41%). The persistence of disturbances in patients with migraine accompagnee was longer than in patients with classical migraine. In comparison to the controls a significantly more frequent occurrence of pathological results was found in patients with migraine accompagnee and classical migraine during the attack as well as during the interval. The age of patients, duration of the migraine and frequency of attacks did not influence the extend of EEG changes. The EEG revealed in patients with migraine significantly more frequent functional disturbances than in controls, which were more pronounced in patients with migraine accompagnee and during the attacks. PMID- 3095093 TI - [Comparison of masked and endogenous depression using psychometric scales, endocrinological markers and pharmacological responses. Masked depression versus endogenous depression]. AB - Masked depression refers to a concept of a phenomenological state, either endogenous or psychogenic where somatic symptoms replace sadness: Thirty patients were evaluated by RDC (22 endogenous and 8 masked depressions) wherein in the latter dysphoria was replaced by a nonreactive persistent somatic complaint. They were rated on Beck and Hamilton Depression Scales, on Hamilton and Trait-State Anxiety Scales and the NOSIE. All patients presented with insomnia, anorexia, loss of weight, diminished libido and anhedonia. Initial ratings were similar for both diagnostic groups except for a significantly higher agitation factor and lower retardation in masked depression. Although 59.9 percent of the subjects are positive on the dexamethasone test, only 1 masked depression did not suppress secretion of cortisol. After a randomized 30-day drug trial where patients were assigned to Clomipramine or Desipramine, patients in both groups show significant improvement on rating scales but diagnostic group drug treatment interaction exists on anxiety and agitation criteria. PMID- 3095094 TI - Measurement of a follicle-stimulating hormone-responsive protein of Sertoli cell origin using an enzyme-linked immunoblot assay. AB - Many proteins secreted by Sertoli cell-enriched cultures are maximally stimulated by a combination of FSH and testosterone. Since very few are stimulated primarily by FSH, we thought it pertinent to identify such proteins. Sertoli cell-enriched cultures were prepared from testes of 20-day-old rats and grown in serum-free medium containing insulin, transferrin, and epidermal growth factor and in such medium supplemented with FSH, testosterone, or FSH plus testosterone. Media were fractionated using HPLC, and proteins were identified by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. A protein designated CMB-2, with an apparent mol wt of 22,000, was shown to increase in response to FSH. Antiserum was raised using denatured protein eluted from SDS-polyacrylamide gels as the antigen, and a specific immunoassay using a combination of SDS-polyacrylamide gel electrophoresis and Western blotting was developed. The production of CMB-2 by primary Sertoli cell-enriched cultures was found to increase in a dose-dependent manner in response to FSH (30-1000 ng/ml); secretion was not significantly affected by testosterone (2 X 10(-13) M). An investigation of the tissue distribution of CMB-2 showed that the puberty, CMB-2 is secreted into the rete testis and accumulates in the epididymis in high concentration. We conclude that CMB-2 will be a useful marker to study the action of FSH on the rat testis. PMID- 3095095 TI - A direct pituitary action of progesterone on basal secretion of follicle stimulating hormone in ovine cell culture: dependence on ovaries in vivo. AB - Progesterone (P4) inhibits FSH production by 60-70% in cell cultures of pituitaries from normal ewes. This communication reports that P4 is much less effective in inhibiting FSH production in cultures prepared from pituitaries of ovariectomized ewes. P4 (10(-7) M) inhibited 61 +/- 5% of basal FSH secretion in cultures from intact anestrous ewes. When cultures were prepared from pituitaries collected on day 9, 21, or 42 after ovariectomy, P4 inhibited FSH secretion by only 46 +/- 3%, 16 +/- 2%, and 10 +/- 2%, respectively. One group of ewes received implants of 17beta-estradiol (E2) at the time of ovariectomy. When cultures were prepared from these ewes 35 days after ovariectomy, P4 inhibited FSH secretion 56 +/- 5%, not significantly different (P greater than 0.05) from inhibition in normal cultures. Furthermore, under similar culture conditions, E2 and a porcine ovarian inhibin preparation inhibited FSH secretion regardless of the length of time after ovariectomy. These in vitro results suggest that ovariectomy causes a time-dependent decrease in pituitary responsiveness to P4 in vivo. Since E2 can maintain P4 sensitivity in pituitaries from ovariectomized ewes, E2 may be the only ovarian factor required to maintain pituitary responsiveness to P4 in vivo. PMID- 3095096 TI - The effect of transient dopamine antagonism on thyrotropin-releasing hormone induced prolactin release in pregnant rats. AB - The effect of transient dopamine (DA) antagonism on the sensitivity of pituitary lactotrophs to the PRL-releasing effect of TRH was investigated in rats on days 3, 9, 15, and 21 of pregnancy. Each animal, bearing an indwelling intraatrial catheter, received injections of either the DA antagonist domperidone (0.01 mg/rat, iv) or saline at 0930 h on the day of the experiment. Five minutes later, all animals were given the DA agonist 2-bromo-alpha-ergocryptine maleate (CB-154; 0.5 mg/rat, iv), followed 60 min later by the administration of TRH (1.0 microgram/rat iv). Plasma samples obtained during the experiment were assayed by RIA for PRL and progesterone (P). The results showed that transient DA antagonism increased the sensitivity to TRH as a PRL-releasing stimulus on the morning of day 3 of pregnancy, but not on days 9 and 15. However, the response was present on day 9 in animals that were hysterectomized (HS) on day 6 of pregnancy. The increase in sensitivity of lactotrophs to TRH after DA blockade was observed on day 21 of pregnancy. Plasma levels of P were high on days 3, 9, and 15, but decreased markedly by day 21. In a second experiment, the anterior pituitary (AP) PRL content was determined on days 3, 9, 15, and 21 of pregnancy. The results demonstrated that AP PRL significantly decreased between days 3 and 9 of pregnancy in both intact and HS animals. However, AP PRL concentrations in animals killed on days 15 and 21 were significantly greater than that on day 9 but were not different from that observed on day 3 of pregnancy. We conclude that the ability to transform AP PRL to a TRH-releasable pool by the transient blockade of DA is present in early and late pregnancy, but is absent in midpregnancy. Since this secretory mechanism is retained on day 9 after hysterectomy on day 6 of pregnancy, it appears that the secretory products of the uterine-placental unit are inhibitory to transformation. Further, this inhibitory effect at midpregnancy cannot simply be the result of decreased AP PRL content or changes in plasma P. Finally, the return of the transformation mechanism on the day before parturition (day 21) may be due to the increase in estrogen secretion that occurs in late pregnancy, since we have previously shown that estrogen can induce this AP secretory mechanism. PMID- 3095097 TI - The effects of transient dopamine antagonism on thyrotropin-releasing hormone induced prolactin release in pseudopregnant rats. AB - The effectiveness of TRH in releasing PRL after transient dopamine (DA) blockade was investigated in female rats between days 3 and 11 of pseudopregnancy (PSP). At 0930 h on the morning of the experiment, each animal was injected with the DA antagonist domperidone (0.01 mg/rat, iv) or vehicle (acetic acid in saline); 5 min later, the DA agonist 2-bromo-alpha-ergocryptine maleate (CB-154; 0.5 mg/rat, iv) was administered. Sixty minutes later, TRH (1.0 micrograms/rat, iv) was administered. Blood samples were withdrawn via indwelling catheters before, 5, 20, 40, and 70 min after domperidone or vehicle administration, and 5 and 10 min after TRH administration. On day 3 of PSP, TRH-induced PRL release was significantly enhanced by the domperidone-CB154 treatment compared to that in vehicle-treated control rats. By day 9 of PSP, the effectiveness of TRH in stimulating PRL release after domperidone treatment was decreased by 50% compared to that on day 3 of PSP. This reduction in PRL response to TRH was not due to decreased progesterone levels, as no difference was observed in plasma progesterone between days 3 and 9. Rats that were given domperidone on day 11 of PSP did not exhibit a significant increase in sensitivity to TRH; however, the effectiveness of TRH was enhanced by domperidone on day 11 of PSP in animals that were hysterectomized on day 2 of PSP. Since DA receptor blockage increased the sensitivity to a putative PRL-releasing factor (TRH) and this mechanism was eliminated around the time that the PRL surges of PSP disappear, we suggest that this pituitary mechanism is a critical component of the PRL release mechanism during the surges of PSP. Further, the observed loss of the mechanism between days 9 and 11 of PSP may be due to the direct influence at the anterior pituitary of a uterine PRL inhibitory factor which has been recently described. PMID- 3095098 TI - The effect of transient dopamine antagonism on thyrotropin-releasing hormone induced prolactin release in ovariectomized rats treated with estradiol and/or progesterone. AB - PRL release was studied in ovariectomized (OVX) rats pretreated with estradiol benzoate (EB), progesterone (P), or a combination of both steroids using a protocol that was selected to mimic ovarian steroid changes that have been observed during the female rat 4-day estrous cycle and early pregnancy. On the morning of the experiment, the animals received injections of either the dopamine (DA) antagonist domperidone (0.01 mg/rat iv) or vehicle (acetic acid in saline). Five minutes later, all animals received injections of the DA agonist 2-bromo alpha-ergocryptine (CB-154; 0.5 mg/rat, iv) followed 60 min later by the administration of TRH (1.0 microgram/rat, iv). Plasma obtained from blood samples taken during the experiment was assayed for PRL by RIA. In OVX or P-treated OVX rats, a transient blockade of DA by domperidone did not alter the sensitivity of the pituitary to TRH administration, as measured by an increase in plasma PRL. However, such an effect of DA blockade was induced by 2 days of EB treatment and was maintained and amplified by P administration after EB injections. We conclude that enhancement of the PRL-releasing effect of TRH by DA antagonism, a mechanism we previously observed in female rats during midlactation, proestrus, estrus, and metestrus using the present drug protocol, can be induced by estrogen and maintained by P. Further, our data suggest that the previously observed loss of this secretory mechanism on the morning of diestrus may be due to the decrease in plasma P that takes place between metestrus and diestrus. PMID- 3095099 TI - Stimulation of growth hormone release and synthesis by estrogens in rat anterior pituitary cells in culture. AB - We have investigated the potential effect of estrogens in the control of GH secretion in rat anterior pituitary cells in primary culture. We have found that a 72-h preincubation with 17 beta-estradiol (E2) caused an approximately 2- to 3 fold stimulation of basal and GH-releasing factor (GRF)-induced GH release as well as cellular GH content at EC50 values of 44, 35, and 15 pM, respectively. Estrone and estriol also increased GH release at respective EC50 values of 100 and 250 pM. The stimulatory effects of these steroids on GH release and cellular GH content were competitively blocked by simultaneous incubation with the antiestrogen LY156758. In contrast to thyroid and glucocorticoid hormones, a 72-h pretreatment with E2 failed to potentiate GRF-induced cAMP accumulation or enhance the sensitivity of the GH response to GRF. However, E2 increased the stimulatory effect of submaximal concentrations of dexamethasone on spontaneous and GRF-induced GH release as well as on total GH, but did not further increase the effect of maximal dexamethasone concentrations. As determined by a 60-min pulse labeling with [35S]methionine performed after a 72-h preincubation with E2, GH and PRL synthesis were increased by about 50% above control values (P less than 0.005). The present data clearly indicate for the first time that E2, at physiological concentrations, exerts a stimulatory effect on spontaneous and GRF induced GH release as well as on cellular GH content, probably resulting, at least in part, from stimulation of GH synthesis. PMID- 3095100 TI - Ovarian responses in macaques to pulsatile infusion of follicle-stimulating hormone (FSH) and luteinizing hormone: increased sensitivity of the maturing follicle to FSH. AB - This study investigated the relationship between plasma gonadotropin concentrations and the initiation and maintenance of preovulatory follicular growth in macaques. Eight adult cynomolgus monkeys were treated with a GnRH antagonist [AcD2Nal1-4ClDPhe2, DTrp3, DArg6, DAla10]GnRH X HOAc to block endogenous gonadotropin secretion. In four animals, a pulsatile infusion of human FSH and human LH (hLH) (one 3-min pulse/h) was initiated, and the amount of hFSH delivered per pulse was increased every 3-4 days until serum estradiol concentrations rose. Thereafter, the amount of FSH delivered per pulse was reduced by 12.5%/day for 5 days, whereas the amount of LH delivered per pulse was not altered. Results indicated that plasma FSH concentrations in the range of 15 20 mIU/ml were associated with the initiation of estrogen production; in addition, a progressive reduction in plasma FSH concentration to 8-10 mI/ml over the subsequent 5 days was accompanied by continued rises in estradiol concentrations and preovulatory follicular growth. In contrast, in four control animals, maintenance of plasma FSH concentrations at 8-10 mIU/ml for 13 days did not result in elevation in serum estradiol concentrations or antral follicular growth. These observations demonstrate that after stimulation by elevated FSH concentration, follicles can continue to mature in the presence of FSH concentrations which are unable to support the growth of less mature follicles. Thus, this may account for the mechanisms by which the maturing follicle continues to develop during the mid-through late follicular phase of the menstrual cycle, whereas other less mature follicles undergo atresia. PMID- 3095101 TI - Polyamines and autocrine control of tumor growth by prolactin in experimental breast cancer in culture. AB - We have previously observed that both polyamines and an autocrine mechanism are involved in the stimulation by ovine PRL (oPRL) of growth of the N nitrosomethylurea-induced rat mammary tumor cultured in vitro in the soft agar clonogenic assay. These experiments were designed to test the interaction between these two pathways of oPRL action in this system. In agreement with previous findings in our laboratory, conditioned medium obtained from oPRL-treated (oPRL CM), but not untreated, tumors consistently stimulated colony formation when added to N-nitrosomethylurea mammary tumors plated in soft agar under serum-free medium conditions. Administration of alpha-difluoromethyl-ornithine (DFMO), an irreversible inhibitor of polyamine biosynthesis, abolished the colony stimulating effect of oPRL-CM. The inhibitory effect of DFMO was reversed in a dose-dependent fashion by the addition of spermidine, which entirely restored the growth-promoting action of oPRL-CM. In addition, the administration of increasing amounts of spermidine potentiated the colony-stimulating effect of suboptimal concentrations of oPRL-CM. In contrast, manipulation of the polyamine environment with DFMO and/or spermidine administration did not affect the number of colonies formed when conditioned medium from untreated tumors was added instead of oPRL CM. We conclude that the polyamine pathways plays an essential role in the expression of autocrine control of tumor growth by oPRL. PMID- 3095102 TI - Triiodothyronine repression of imidazole-induced tyrosinase expression in B16 melanoma cells. AB - Investigations with mouse melanoma B16/C3 cell cultures have suggested that imidazole or a derivative thereof can facilitate expression of the tyrosinase (EC 1.14.18.1) structural gene. The induction of tyrosinase expression by imidazole was inhibited by T3 about 4-fold. When T3 (10 nM) was present for 19 h in proliferating B16/C3 cultures, basal activity of this enzyme was inhibited by approximately 60%. Neither T3 nor imidazole directly affected tyrosinase enzymatic activity in broken cell preparations. Addition of T3 to imidazole induced cultures rapidly decreased tyrosinase expression (within 30 min) which remained repressed for at least 4 h before recovering. Recovery of tyrosinase activity could be blocked by readdition of hormone. The hormone effect was detectable at 1 nM and was maximal at 10 nM. Removal of supplemental T3 from the medium rapidly reversed the repression of tyrosinase activity. The biologically inactive analog rT3 (10 nM) failed to inhibit basal enzyme activity or alter the imidazole effect on tyrosinase expression. The experimental results with protein and RNA inhibitors indicate that the T3 response is independent of destabilizing the putative transcript for tyrosinase or altering the posttranslational events responsible for its synthesis. PMID- 3095103 TI - Guanine triphosphate-binding site regulation by follicle-stimulating hormone and guanine diphosphate in membranes from immature rat Sertoli cells. AB - GTP binding to Sertoli cell membranes has been investigated using [3H]5'-guanylyl beta gamma-imidodiphosphate [[3H]Gpp(NH)p], a nonhydrolyzable analog of GTP. Binding of [3H]Gpp(NH)p Gpp(NH)p to membranes prepared from Sertoli cells in serum-free culture was proportional to membrane protein concentration in the range of 5-50 micrograms. Competitive displacement studies using adenine (ATP, ADP, and AMP) and guanine nucleotides [GTP, GDP, GMP, and Gpp(NH)p] indicated that only GTP, its analog Gpp(NH)p, and GDP were effective ligands. The relative potencies were Gpp(NH)p much greater than GTP greater than GDP, as characterized by ED50 values of 0.8, 2.5, and 4 microM, respectively. Competitive inhibition by GTP, however, was similar to that by Gpp(NH)p in the presence of a nucleoside triphosphate-regenerating system, suggesting the involvement of an active GTPase. Equilibrium binding studies indicated a single high affinity site for GTP with a Ka of 3.3 +/- 0.2 X 10(7) M-1. This value was supported by other studies in which an association rate constant of 1.8 X 10(6) M-1 min-1 and a dissociation rate constant of 2.4 X 10(-2) min-1 were estimated. Maximal binding of [3H]Gpp(NH)p to Sertoli cell membranes ranged from 30-55 pmol/mg protein. FSH enhanced [3H]Gpp(NH)p binding by about 50% (P less than 0.05), reflecting an increase in the number of available binding sites rather than an effect on Ka. When GDP was preincubated with membranes in the absence of FSH, the number of available binding sites for [3H]Gpp(NH)p was decreased. This reduction in available binding sites by pretreatment with GDP could be reversed by adding FSH during the equilibrium binding analysis. These studies have demonstrated specific high affinity binding of Gpp(NH)p to Sertoli cell membranes with an affinity comparable to that required for activation of FSH-sensitive adenylate cyclase. Furthermore, a potent GTPase activity associated with the Sertoli cell membrane is responsible for rapid hydrolysis of GTP to GDP and may participate in inactivation of GTP-dependent adenylate cyclase activity. The role of FSH in the regulation of nucleoside binding appears to be in facilitating exchange of GTP for GDP by enhancing the release of bound GDP. PMID- 3095104 TI - Coupling of adenylate cyclase to lipolysis in permeabilized adipocytes: direct evidence that an antilipolytic effect of insulin is independent of adenylate cyclase. AB - In digitonin-permeabilized adipocyte suspensions, adenylate cyclase activation was analyzed by an in situ assay and compared to lipolytic activity which was determined under essentially identical assay conditions. This approach permitted direct comparison of the regulatory responses of these two processes. Adenylate cyclase was activated by isoproterenol in permeabilized adipocytes, but digitonin caused a decrease in sensitivity to the beta-agonist. On the other hand, activation of adenylate cyclase by forskolin and NaF was unaffected by digitonin. Inhibition of isoproterenol-activated adenylate cyclase by propranolol was also unaffected by digitonin. These observations are consistent with a partial uncoupling by digitonin of the interaction between occupied beta-adrenergic receptors and the stimulatory GTP-binding component (Ns). Despite permeabilization, adenylate cyclase activity retained the capability to activate the lipolytic pathway. Activation of adenylate cyclase and lipolysis by isoproterenol was first detectable at 10(-8) M. At 10(-7) M isoproterenol, when the cyclase activity increase was 11 pmol cAMP formed/min X 10(6) cells (21% increase over basal), lipolysis was increased 153%. Forskolin was a more effective activator of adenylate cyclase than isoproterenol, increasing activity maximally by greater than 7-fold in contrast to a maximum of 4.5-fold activation by the beta-agonist. Forskolin-dependent adenylate cyclase activity increased by 63 pmol cAMP/min X 10(6) cells, however, before an increase in lipolysis was first detected (33% increase). Thus, cAMP generated by the two lipolytic agents was not identical in its lipolytic potential. Maximum rates of lipolysis were equal for the two agents. Insulin (10(-9) M) exerted an antilipolytic effect on lipolysis in permeabilized adipocytes whether the lipolytic activator was isoproterenol or forskolin. At 10(-6) and 10(-4) M isoproterenol, the magnitudes of the antilipolytic effect were 35% and 21%, respectively, whereas forskolin activated lipolysis (at 10(-6) M) was inhibited 22%. Insulin had no effect on adenylate cyclase activity stimulated by either agent and assayed under essentially identical conditions. In summary, direct comparison of adenylate cyclase activity and lipolysis in digitonin-permeabilized adipocytes demonstrated a more efficient coupling of adenylate cyclase to lipolysis when the enzyme was activated by isoproterenol rather than forskolin. Additionally, the antilipolytic effect of insulin was preserved in the permeabilized adipocytes, but this effect did not involve inhibition of adenylate cyclase. PMID- 3095105 TI - Inhibition of follicle-stimulating hormone/diethylstilbestrol-stimulated ovarian growth by extracts of pregnancy urine. AB - We devised an in vivo biological assay for ovarian growth inhibiting activity to examine extracts of human pregnancy urine for the presence of ovarian growth inhibiting factor. Diethylstilbestrol (DES) capsules were implanted sc in immature hypophysectomized female rats; FSH was injected sc with or without test substance for 5 days. Rats with unstimulated ovaries were implanted with blank capsules and given the vehicle without FSH. Twenty four hours after the last injection, the ovaries were removed and weighed. The ovarian growth inhibition of the ovarian weight gain achieved in rats treated with DES and FSH. Crude commercial human CG (hCG) preparations, extracted from pregnancy urine, were chromatographed on Sephadex G-100, and the fractions were tested for ovarian growth inhibiting activity. The peak of ovarian growth inhibiting activity was found in fractions eluting from the column in the mol wt range of 12,000-20,000. Ovarian growth inhibiting activity was heat sensitive, not extracted by ether, and precipitated by acetone. Ovarian growth inhibiting activity was stable in acid at pH 2, but was inactivated by digestion with trypsin. The ovarian growth inhibiting activity was purified by chromatography on Concanavalin A-Sepharose and diethylaminoethyl-Sephacel. The active material contained hCG alpha, hCG beta, and beta-carboxyterminal peptide-immunoreactivity and its inhibiting activity could be removed from solution by immunoadsorption with antisera specific for hCG beta. The ovarian growth inhibiting activity was further purified on an anti-hCG alpha-immunoglobulin G affinity column. The activity was eluted from the affinity column at low pH, and eluted material contained all of the immunodeterminants of hCG. Virtually identical dose-response curves of ovarian inhibition were obtained using equivalent doses of beta-carboxyterminal peptide immunoreactivity of purified inhibitor and purified hCG (CR123). The inhibiting activity reached plateau of 80-90% at doses of 50-100 ng hCG/rat. Upon rechromatography on Sephadex G-100, the ovarian growth activity that was pooled from fractions corresponding to the 12,000-20,000 mol wt range was recovered in fractions corresponding to the elution position of hCG. We conclude that the low mol wt inhibiting activity observed in the crude pregnancy extracts is due to hCG and that hCG is a very potent inhibitor of FSH/DES stimulation of ovarian growth. PMID- 3095106 TI - Calcitonin gene-related peptide in thyroid nerve fibers and C cells: effects on thyroid hormone secretion and response to hypercalcemia. AB - Calcitonin gene-related peptide (CGRP) in the thyroid has a dual localization to nerve fibers around blood vessels and follicles and to parafollicular (C) cells. CGRP was found to coexist with substance P (SP) in most of the nerve fibers; a few CGRP fibers seemed to lack SP, and a few SP fibers seemed to be devoid of CGRP. In the C cells, CGRP coexisted with calcitonin (CT). Cervical vagotomy (extirpation of the nodose ganglion) eliminated approximately 50% of the CGRP/SP fibers in the thyroid without any overt influence on CGRP/CT in the C cells. Removal of the superior cervical ganglion or chemical sympathectomy (6 hydroxydopamine treatment) affected neither thyroid CGRP/SP nerve fibers nor CGRP/CT-storing C cells. CGRP nerve cell bodies were numerous in the jugular nodose ganglionic complex (notably in the jugular portion); in many of them, CGRP coexisted with SP. A few scattered CGRP nerve cell bodies also occurred in the laryngeal ganglion, whereas none was found in the thyroid ganglion. Hypercalcemia evoked by vitamin D2 treatment, which is known to degranulate thyroid C cells, reduced the thyroid content of both CGRP and CT. As tested in mice in vivo, CGRP and SP alone or together had no effect on basal or TSH- or isoprenaline-induced thyroid hormone secretion. Vasoactive intestinal peptide-stimulated iodothyronine release, on the other hand, was enhanced by CGRP, but not by SP. SP had no effect on combined vasoactive intestinal peptide-CGRP-stimulated iodothyronine release. These findings suggest that CGRP participates in the control of thyroid hormone secretion and that, like CT, CGRP in the C cells is under control of the serum calcium level. PMID- 3095107 TI - Inhibition of follicle-stimulating hormone induction of aromatase activity in porcine granulosa cells by thyroxine and triiodothyronine. AB - We examined the effects of T3 and T4 on basal and FSH-induced aromatase activity in granulosa cells isolated from medium-sized follicles (4-6 mm) of prepubertal pigs. Treatment of cells with T3 or T4 alone during an initial 48-h induction period did not result in any significant change in aromatase activity, as measured by 17 beta-estradiol accumulation during the subsequent 6-h test period, when testosterone (0.5 microM) was added as substrate. However, when cells were cultured with FSH and T3 or T4 during the induction period, a definite dose dependent inhibition of FSH-induced aromatase activity was demonstrated. This inhibition was not altered by the presence of a binding protein (BSA). The inhibition of FSH-induced aromatase activity by T4 and T3 is a true biological effect, as inactive iodocompounds (MIT and DIT) and iodide had no significant effect on the gonadotropin-induced aromatase activity. Furthermore, the viability of cells was unaffected by the thyroid hormones, and total cellular protein did not change significantly. These results indicate that thyroid hormones might play an important role in modulating FSH-induced aromatase activity, and that the elevated plasma estrogen levels in some cases of hyperthyroidism are not due to increased ovarian secretion. PMID- 3095108 TI - Patterns of mutagen binding and penetration in multicell spheroids. AB - Mutagen damage to a cell located at some distance from the site of application of the mutagen will depend, in part, on how effectively it can penetrate through cells composing different tissues. Chinese hamster V79 spheroids were used to model mutagen "penetrability" by providing several layers of cells growing with tissue-like packing. By treating cells of intact and trypsin-dissociated spheroids at the same drug-to-cell ratio, an estimate relative sensitivity to nine mutagens was determined. The effective toxicity index (ETI) was defined as the ratio of the concentrations of mutagen required to kill 50% of cells (measured after a 1-hr treatment at 37 degrees C) in dissociated versus intact spheroids and similarly for mutation at the HGPRT locus (EMI). Values for ETI were consistent with values for EMI and varied from 0.01 for 4NQO to 2 for AF-2. Direct information on mutagen penetration was obtained for fluorescent mutagens by flow cytometry. Values for EFI (effective fluorescence index) varied from 0.07 for Hoechst 33342 to 1 for AF-2. These results can be interpreted as reflecting differences in ability of mutagens to penetrate spheroids; some direct-acting mutagens are likely to be effective only near their site of application (ie, UV, Hoechst 33342, 4NQO) while others are able to penetrate through successive cell layers with little difficulty (ie, monobromobimane, AF-2). PMID- 3095109 TI - Observations on the long term effects of Brucella abortus infection in the horse, including effects during pregnancy and lactation. AB - Five mares and a stallion were studied from three to 30 months after experimental infection with Brucella abortus strain 544. The mares bred normally. No organisms were recovered from horses or from pregnant Friesian heifer contacts. Titres of serum antibody in the antiglobulin (Coombs) and complement fixation tests fell more slowly than those assessed by other tests. The serum of one foal yielded maternal antibody. An intradermal test was positive in infected adults only, and negative in all foals. PMID- 3095110 TI - Thermogenic effect of food in physically well-trained elderly men. AB - Basal metabolic rate (BMR) and the thermogenic effect of food (TEF) after a liquid mixed meal of 2092 kJ (500 kcal) were examined in physically well-trained, elderly men in comparison with sedentary weight- and age-matched controls. BMR tended to be higher and TEF was significantly higher in the physically well trained men than in the controls. No certain differences were found in plasma thyroid hormones or catecholamines. BMR correlated with whole body potassium while TEF did not. The tendency to elevated BMR in the well-trained men might therefore be due to their greater muscle mass. The elevated TEF, however, probably has other causes and might be associated with the elevated catecholamine sensitivity associated with the physically trained condition. PMID- 3095112 TI - Non-invasive assessment of cardiac output and stroke volume in patients during exercise. Evaluation of a CO2-rebreathing method. AB - A one-step CO2 rebreathing method for the determination of cardiac output and stroke volume (SV) has been evaluated by comparison with the direct Fick technique during recumbent exercise (10-90 W) in 13 patients. In an initial analysis, the influence of different rebreathing times and of correction for haemoglobin concentration was studied. The best correlation with the direct Fick technique was obtained with the longest analysis time, i.e. 21 s, and correction for variations in haemoglobin concentration further improved the correlation. Consequently, an analysis time of 21 s and correction for haemoglobin have been used. At low cardiac outputs, the CO2-rebreathing method overestimated the flow compared to the Fick technique. The correlation between the methods, however, was so good that a valid estimate of cardiac output could be obtained from the CO2 rebreathing method with appropriate corrections (Cardiac output, CO2 method = 2.7 + 0.77. Cardiac output, Fick; r = 0.91; Residual Standard deviation (SD res) = 0.77 l X min-1). Stroke volumes measured with the CO2 rebreathing method did not differ significantly from those obtained with the direct Fick technique, although there was a tendency to overestimate stroke volume with the CO2 rebreathing method (SV, CO2 method = 12 + 0.89 X SV, Fick; r = 0.82; SD res = 11 ml). PMID- 3095111 TI - The effect of verapamil on cardiovascular and metabolic responses to exercise. AB - In a double-blind cross-over study, the effects of verapamil on the cardiovascular and metabolic changes during a progressive maximal exercise test were studied in 12 healthy volunteers. Each subject was treated with placebo and verapamil in 3 different dosages: 3 X 40, 3 X 80 and 3 X 120 mg X d-1 in random order. Drugs were administered for 2 days; on the 3rd day, 2 h after the last dose, a progressive exercise test until exhaustion was performed on a bicycle ergometer. No significant differences in maximal exercise capacity were found between the 4 groups of medication. VO2, VCO2, and VE were also unaffected by verapamil administration. Heart rate during exercise was reduced dose-dependently (p less than 0.001). With the highest dose of verapamil, maximal heart rate was reduced by 13 +/- 1 beats X min-1. No effect could be shown on parameters of carbohydrate and fat metabolism. Perceived exertion, estimated by the Borg scale, did not differ between placebo and the 3 medication groups. The study shows that despite a distinct reduction of heart rate, maximal exercise capacity remains unaffected after verapamil use. PMID- 3095113 TI - Lysine-containing DNA-binding regions on the surface of the histone octamer in the nucleosome core particle. AB - The DNA bound on the surface of the histone octamer in the nucleosome core particle partially protects the epsilon-amino side-chains of a subset of the lysine residues from reductive methylation. Most of the strongly protected lysines, which probably define the path of the DNA on the octamer surface, are in the globular ('structured') regions of the core histones rather than in the N terminal or C-terminal 'tails'. Analysis of the protected peptides shows that the three strongest lysine-containing DNA-binding sites in the core histones contain the sequence-Lys/Arg-Lys-Thr/Ser-. On the assumption that the lysine-containing regions protected from chemical modification are also those found in lysine-DNA cross-links in another study [Mirzabekov et al. (1978) Proc. Natl Acad. Sci. USA 75, 4184-4188], particular DNA-protected peptides may be tentatively assigned to particular DNA contact points. This leads to a more detailed description of the DNA-binding regions on the octamer surface in the nucleosome core particle. Strong contacts, reflected in strongly protected lysines, may well contribute to the distortion of the DNA from smooth bending [Richmond et al. (1984) Nature (Lond.) 311, 532-537]. PMID- 3095114 TI - 1H and 13C NMR assignment of benzothiophenquinones from the sulfur-oxidizing archaebacterium Sulfolobus solfataricus. AB - From Sulfolobus solfataricus, a sulfur-oxidizing thermophilic member of archaebacteria, three unusual benzothiophenquinones were isolated. Detailed NMR studies on these quinones, including multipulse mono-dimensional and two dimensional techniques, were performed to obtain carbon and proton assignments, one-bond, geminal and vicinal coupling constants and T1 relaxation times. This report extends the known quinone composition of thermophilic archaebacteria and further supports the concept that these biomolecules can serve as a useful chemotaxonomic tool. PMID- 3095115 TI - The primary structure of apolipoprotein A-I from rabbit high-density lipoprotein. AB - The amino acid sequence of rabbit apolipoprotein A-I (apo A-I) has been determined by degradation and alignment of two overlapping sets of peptides obtained from tryptic and staphylococcal digestions. All of the peptides of rabbit apo A-I resulting from digestion by staphylococcal protease were isolated and sequenced except residues 33-37. A digestion with trypsin was employed to find overlapping and missing peptides. The N-terminus of rabbit apo A-I was confirmed by sequencing the intact protein up to 20 residues while the C-terminus was identified through its homology with human apo A-I. The protein contains 241 residues in its single chain. Its primary structure is highly homologous to the reported canine apo A-I (80%) and human apo A-I (78%), but exhibits less similarity with rat apo A-I (60%). Like human apo A-I, rabbit apo A-I contains very little histidine (2) and methionine (1); it does however have two residues of isoleucine. Based on a comparison of the hydrophobic-hydrophilic character of apo A-I residues with that of the two synthetic peptides that activated lecithin: cholesterol acyltransferase (Pownall et al. and Yokoyama et al.), we found that the five segments with the highest corresponding homologies on the protein are located within the N-terminal half. This suggests that the N-terminal half of apo A-I contains the major portion of regions activating lecithin: cholesterol acyltransferase. PMID- 3095116 TI - Interventional radiology with venous port (chemotherapy and infusional support). AB - A completely portable permanent central venous access, consisting of a steel capsule sealed with a silicone membrane and connected to a silicone catheter (Port-a-Cath), was implanted in the subcutaneous tissue of 36 patients, most of whom no longer had accessible peripheral veins and needed to continue chemotherapy or undergo total parenteral nutrition. The access vessel was mostly the subclavian vein and the capsule was sutured to the pectoral fascia. Total subcutaneous implantation seems to afford optimum safety from infection and freedom for personal hygiene, produced no noteworthy complications and proved relatively simple to maintain. PMID- 3095117 TI - Onset time of action and duration up to 3 hours of nitroglycerin in buccal, sublingual and transdermal form. AB - Nitroglycerin in sublingual, buccal and transdermal administration forms were compared in 10 patients with stable exercise-induced angina pectoris with respect to onset time of action and efficacy one and three hours after administration, using bicycle exercise to provoke chest pain. Anti-anginal and anti-ischaemic effects (as judged by influence on electrocardiographic ST depression) began within 2 minutes of application of the buccal and sublingual forms, whereas the transdermal patch did not show such effects within nine minutes of application. One and three hours after application, the sublingual form had no effect whereas both the transdermal and buccal forms significantly increased exercise capacity and improved electrocardiographic ST segment changes. The 2.5 mg buccal tablet was more effective than the 10 mg transdermal patch. An additional observation was that a light snack at 2 hours significantly decreased exercise capacity at 3 hours whether or not active treatment had been instituted. PMID- 3095118 TI - Assessment of myocardial metabolism by PET--a sophisticated dream or clinical reality? PMID- 3095119 TI - Studies of gonadotrophin pulsatility and pelvic ultrasound examinations distinguish between isolated premature thelarche and central precocious puberty. AB - We have studied the pulsatile secretion of gonadotrophins at night and made ovarian ultrasound examinations in three girls with central precocious puberty and three with isolated premature thelarche. The three girls with precocious puberty had well-defined pulsatile secretion of LH and FSH with LH predominating, as would be expected in normal puberty. Pulsatile secretion of gonadotrophins was also seen in girls with premature thelarche but the pattern was reversed. In girls with precocious puberty, large "multicystic" ovaries and large uteri were seen on ultrasound examination, whereas girls with isolated premature thelarche had small uteri and ovaries with less than four "cysts" up to 15 mm in diameter. These data provide the key to understanding the aetiology of isolated premature thelarche. PMID- 3095121 TI - Prediction of ifosfamide/mesna associated encephalopathy. AB - Ifosfamide and mesna were administered to 77 patients with advanced malignancies. Seven (9%) experienced a severe but reversible encephalopathy. In 56% of patients in whom EEG data was available, characteristic changes were seen with or without mild clinical toxicity. Discriminant analysis identified low serum albumin concentration, high serum creatinine concentration and the presence of pelvic disease as variables which predispose patients to the development of severe encephalopathy. A nomogram has been constructed which can be used to determine the probability that an individual patient may be given ifosfamide and mesna safely. This has important implications for the clinical use of a highly active chemotherapy regimen. PMID- 3095120 TI - New aspects of oestrogen/gestagen-induced growth and endocrine changes in individuals with Turner syndrome. AB - Patients with Turner syndrome (n = 33) were subjected to a sequential oestrogen/gestagen replacement therapy (21 days 2 mg oestradiol valerate plus 0.5 mg norgestrel for 10 days) for 1-4 years. In individuals aged 12-17 years, growth velocities before treatment ranged between 2.9 and 1.9 cm/year and increased to 6.8-3.8 cm/year following sex steroid substitution for 1 year. Thereafter a decrease was observed; depending on age, pre-treatment velocities were observed within 2-4 years of replacement therapy. On average, bone age advanced 1 year following 1 year of sex steroid administration and adult bone age was reached following 2-4 years of treatment. Approximately 70% of the individuals noted breast development to stage IV according to Tanner and experienced regular withdrawal bleedings. Oral administration of oestradiol valerate resulted in serum oestradiol levels normally seen during the early follicular phase; hypergonadotropic LH and FSH levels decreased slightly following 1 year of therapy. Growth ranged between 4 and 13 cm; in the oldest individuals the final height ranged between 149 and 156 cm. In summary, the oestrogen/gestagen replacement therapy chosen for this study achieved development of secondary sex characteristics, endocrine changes, growth velocities, bone age advancement and to a certain extent growth, which was almost comparable to that observed during puberty in healthy girls. PMID- 3095122 TI - Erythrocyte polyamine levels during intravenous feeding of patients with colorectal carcinoma. AB - Changes in erythrocyte (RBC) polyamines were studied during total parenteral nutrition (TPN) in 16 colorectal carcinoma patients and six patients with noncancerous diseases. RBC putrescine (PTC), spermidine (SPD), and spermine (SPM) were analyzed before and at the completion of preoperative TPN in each patient. Before TPN, nutritional status, based on a history of weight loss and plasma albumin, prealbumin and retinol-binding protein levels, were similar for the two groups. Initial RBC PTC, SPD, and SPM levels were also similar for both groups. Preoperative TPN induced significant increases in RBC PTC levels (P less than 0.001) and RBC PTC:SPD ratios (P less than 0.005) of the cancer patients while no significant polyamine changes were observed in the other group. Host response to nutritional therapy was monitored with plasma prealbumin and retinol-binding protein levels which did not change significantly in either group. PMID- 3095123 TI - Modulation of c-fos and c-myc mRNA levels in normal human lymphocytes by calcium ionophore A23187 and phorbol ester. AB - A transient expression of the proto-oncogenes c-fos and c-myc is rapidly induced by growth factors or mitogens in different cell types including lectin-stimulated lymphocytes. To elucidate the early events of lymphocyte activation, we determined (by Northern blot analysis) the steady-state levels of c-fos and c-myc mRNA in normal human peripheral blood lymphocytes (PBL) stimulated with the Ca2+ ionophore A23187 and/or 12-O-tetradecanoylphorbol-13-acetate (TPA), whose biological activities are well defined. We report that ionophore A23187 (0.5 microM) or, to a significantly lesser extent, TPA (0.5 ng/ml), neither of which is mitogenic alone at these concentrations, nevertheless can induce a transient accumulation of the proto-oncogene transcripts. These results indicate that a significant accumulation of c-fos and c-myc mRNA can occur without subsequent lymphocyte proliferation. The combination of these two mitogens increases the induced levels of both types of c-onc mRNAs. The level of mRNA accumulation correlates with the degree of proliferation induced by mitogenic combinations of ionophore A23187 and TPA, as measured by [3H]thymidine incorporation. Thus, these compounds act synergistically both with respect to c-fos and c-myc mRNA accumulation and to mitogenicity in human PBL. We also studied the level of c-fos transcripts following stimulation of the T lymphocyte T3/Ti receptor complex, using monoclonal anti-T3 antibodies. We observed that mitogenic doses of anti-T3 also induce an accumulation of c-fos mRNA, whose induction also is synergized by TPA. These results suggest that transient accumulation of c-fos; as well as c myc, mRNA is a normal event of the immune response. They confirm that Ca2+ ionophore combined with TPA can mimic some molecular features of the early steps of normal human PBL activation. PMID- 3095124 TI - B cell hyperactivity in systemic lupus erythematosus: selectively enhanced responsiveness to a high molecular weight B cell growth factor. AB - To characterize B cell hyperactivity in systemic lupus erythematosus (SLE) patients we studied the early events of B cell activation in 14 patients and controls. We measured B cell proliferation induced by three interleukin (IL) preparations (20-kDa B cell growth factor, BCGF, recombinant IL2 and 50-kDa BCGF) in the absence and in the presence of an anti-mu antibody (Ab). SLE B cells exhibited a markedly enhanced proliferative response to the 50-kDa BCGF in the absence of an anti-mu Ab, while responding normally in the presence of a first signal. This pattern of hyperactivity was observed in 11 out of 14 patients tested, and was absent in control patients. In contrast, SLE B cells behaved like normal B cells for the response to the other two IL tested, and to the anti-mu Ab alone. It should be pointed out that SLE B cells responded normally to recombinant IL2 whereas T cells from the same patients exhibited a decreased response to this IL. The selectively enhanced responsiveness of SLE B cells to the 50-kDa BCGF suggests that the events leading to B cell hyperactivity in this disease affect the early stages of B cell activation. PMID- 3095125 TI - Leukemic cells arise from cloned cytotoxic lymphocytes during cell culture. AB - In spite of many promising attempts to apply T cell clones to questions of in vitro and in vivo function of T cells it is still unclear to what extent continuous propagation of T lymphocytes in vitro effects their original properties. This study describes the appearance of malignant cells from long-term cultured C57BL/6 (B6) cytotoxic T lymphocytes (CTL). Four out of five T cell lines (CTLL.1,3,4,5) representing distinct stages of development of T effector cells in vitro were repeatedly cloned and all five CTLL were tested for various cellular parameters. It is shown that transformation of H-Y-specific CTLL into malignant cells in vitro was accompanied by alterations in growth characteristics, successive loss of specificity and cytolytic function and by quantitative changes in the expression of cell surface markers. Whereas growth of the H-Y-specific CTLL (CTLL.1) was dependent on antigen and concanavalin A (Con A) supernatant (Con ASN) the CTLL variants could be either maintained in Con ASN alone (CTLL.3) or in the absence of both antigen and lymphokine sources (CTLL.4,5). CTLL.1 was cytolytic for male B6 target cells and lysed P815 tumor targets in the presence but not the absence of lectin. In contrast, CTLL.3 lost its original specificity but lysed P815 cells in the absence or presence of lectin. CTLL.2 representing an intermediary stage showed cytolytic activity on both male B6 and P815 target cells. In contrast, CTLL.4 and CTLL.5 lost the ability to lyse any of the indicated target cells. Although all CTLL expressed the surface markers Thy-1, Lyt-2, Kb, Db and interleukin 2 receptor (IL 2 R), Thy 1 and Lyt-2 markers were drastically reduced and Kb/Db and IL 2 R structures significantly increased on CTLL.4 and CTLL.5 compared to CTLL.1,2,3. In addition, multiple karyotypic alterations including the appearance of metacentric chromosomes were observed in long-term cultured CTLL. Investigations on the expression of the alpha-, beta-, and gamma-chains of the T cell antigen receptor in CTLL.1-5 indicate that all three chains were expressed as mRNA irrespective of whether the lymphocytes expressed their original specificity and/or function. However, distinct beta variable chain genes were used by H-Y-specific CTLL and its long-term culture variants CTLL.2 and CTLL.3 suggesting that the expression of the new specificity was accompanied by the rearrangement of a new beta-chain gene in T effector cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3095127 TI - Immunoglobulin-bearing B cells reconstitute and maintain the murine Ly-1 B cell lineage. AB - Previous reconstitution studies in irradiated mice distinguished Ly-1 B from other B cells. The predominant B cell populations in spleen and lymph node are readily reconstituted from progenitors present in adult bone marrow. Ly-1 B cells, in contrast, are reconstituted from cells in peritoneum rather than bone marrow. Further studies, presented here, demonstrate that Ly-1 B populations are reconstituted from peritoneal cells that already express both surface immunoglobulin (IgM) and Ly-1, that is, Ly-1 B. Such cells reconstitute and maintain the Ly-1 B population in irradiated recipients for at least 6 months. PMID- 3095126 TI - T cell receptor expression and receptor-mediated induction of clonal growth in the developing mouse thymus. High surface beta-chain density is a requirement for functional maturity. AB - The ontogeny of T cell antigen receptor expression and function in the mouse thymus has been studied using a monoclonal antibody, F23.1, which recognizes a determinant on the beta chain of the receptor, and stains 25% of mature T cells and around 7-15% of adult thymocytes from most mouse strains. The same monoclonal antibody selectively activates Lyt-2+ peripheral T cells. Receptors are detectable by staining and fluorescence-activated cell sorter analysis from fetal day 17, and thereafter the overall frequency increases steadily towards adult levels. However, late fetal thymocytes express all of their antigen receptor beta chain at a very low level, visible by staining as a "shoulder" on the peak of negative cells. Thymocytes with high-density surface beta chain, visible by staining as a distinct peak, appear only after birth and are a prominent feature at neonatal day 4. In the late fetus, expression of beta chain can be detected on thymocytes with the "mature" L3T4-, Lyt-2+ phenotype. Despite this, F23.1 responsive precursors are not found in the fetal thymus, and appear in two waves, the first during day 1 of postnatal life and the second between days 3 and 4. These data suggest that high-density surface expression of T cell receptor beta chain occurs in parallel with functional maturation. PMID- 3095129 TI - A protein factor from Bufo marinus erythrocytes cross-bridges microtubules in vitro. AB - A microtubule cross-bridging factor was isolated from erythrocytes of the toad, Bufo marinus. Erythrocytes were lysed and their cytoskeletons disassembled by sonication and high salt extraction. The solubilized proteins were recovered and fractionated using Sephadex G-200 column chromatography. The protein fractions from the column were analysed by SDS-PAGE and pooled into three groups: high molecular weight (HMW) proteins that eluted from the column in the void volume and had a protein composition that included HMW polypeptides; intermediate MW proteins that were shown by SDS-PAGE to contain polypeptides smaller than 120,000 D; and low MW (LMW) proteins that contained polypeptides smaller than 70,000 D. Each group was further fractionated by phosphocellulose (PC) chromatography. The flow-through was recovered, and bound proteins were then eluted by a step gradient of salt (0.2, 0.4, 0.6 and 0.8 M KCl). To assay for microtubule cross bridging activity, column fractions were incubated with taxol-stabilized microtubules, formed from PC-purified brain tubulin (PC microtubules). Negatively stained samples were examined in the electron microscope for the reconstitution of microtubule bundles with interconnecting cross-bridges. The HMW protein fraction from the G-200 column contained the cross-bridging factor. When these proteins were further fractionated by PC chromatography only the fraction eluted by 0.2 M KCl induced the formation of microtubule bundles with cross-bridges. No other protein fraction isolated by the described method revealed cross-bridges between microtubules in vitro. PMID- 3095128 TI - In vitro autoradiographic localization of guanine nucleotide binding sites in sections of rat brain labeled with [3H]guanylyl-5'-imidodiphosphate. AB - In vitro labeling of guanine nucleotide binding proteins has been accomplished for the microscopic localization and quantitation of these sites in individual brain regions. Cryostat sections of rat brain were labeled with [3H]guanylyl-5' imidodiphosphate [( 3H]Gpp(NH)p) using parameters which resulted in a high specific to non-specific (signal to noise) binding ratio. Gpp(NH)p binding sites were identified to some extent in all brain regions examined. The highest densities existed in the olfactory bulb, cerebral cortex, caudate-putamen, interpeduncular nucleus, substantia nigra and cerebellum. Thus, GTP binding proteins can be labeled and localized using a novel application of an autoradiographic technique developed for microscopic detection of receptors. PMID- 3095130 TI - Increased activity of chondroitin sulfate-synthesizing enzymes during proliferation of arterial smooth muscle cells. AB - Cultured arterial smooth muscle cells incorporate [35S]sulfate into the extracellular chondroitin sulfate/dermatan sulfate containing proteoglycans at a higher rate in the phase of logarithmic growth than do non-dividing cells. The cell growth-dependent decrease in 35S incorporation with increasing cell density is accompanied by a decrease in the activity of chondroitin sulfate-synthesizing enzymes. The specific activity of xylosyl transferase, N-acetylgalactosaminyl transferase I and chondroitin sulfotransferase declines as the cells proceed from low to high densities. The corresponding correlation coefficients are 0.86, 0.91 and 0.89. The ratio of C-6OH/C-4OH sulfation of chondroitin shows a cell proliferation-dependent decrease indicating an inverse correlation of chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase activity. The observed changes in the expression of enzyme activities are thought to have some implications in the pathogenesis of arteriosclerosis, the initial stages of which are characterized by proliferation of arterial smooth muscle cells. PMID- 3095131 TI - Purification and characterization of rat bone marrow endothelial cells. AB - A method is described to obtain endothelial cells from rat bone marrow with high purity and viability. Marrow cell suspensions were prepared by collagenase and subjected to discontinuous gradient centrifugation on Percoll (densities 1.04 and 1.06). Endothelial cells were concentrated in the middle layer as demonstrated by electron microscopy and flow cytometry as well as fluorescent microscopy after staining for factor VIII antigen. Cells of this layer were then subjected to centrifugal elutriation and highly purified endothelial cell preparations were obtained with flow rates of 15-20 ml/min. By fluorescent microscopy, 49%-51% of these cells were factor VIII positive. Identification by means of electron microscopy indicated a much higher purity of endothelium ranging from 63% to 90% with a yield in the range of 10(6) cells and a viability exceeding 90%. Some technical considerations in the development of this method are discussed. This method permits in vitro experiments on relatively high purity, high viability preparations of marrow endothelium. PMID- 3095132 TI - Kindling antagonism: effects of norepinephrine depletion on kindled seizure suppression after concurrent, alternate stimulation in rats. AB - The concurrent, alternate electrical stimulation of the entorhinal cortex and septal nucleus results in the development of fully generalized seizures at one electrode site and the suppression of seizure development at the other. We have labeled this phenomenon kindling antagonism. Selective, whole-brain depletion of norepinephrine (NE) virtually eliminates the development of kindling antagonism such that fully generalized seizures develop at both sites in a majority of animals. This effect occurs in the absence of appreciable changes in kindling characteristics of these animals compared with either untreated or vehicle treated controls. These results suggest that the suppression of seizure development observed in the kindling antagonism model is normally maintained by a NE-dependent mechanism. Our results support those of earlier studies using single site kindling paradigms in which NE depletion facilitates the rate of kindled seizure development. We suggest that the NE-dependent mechanism responsible for the seizure suppression observed to follow concurrent, alternate stimulation and the suppression of seizure development using single-site kindling paradigms may be the same. The nature of this NE-dependent seizure suppression mechanism and the anatomic locus or loci critical for this effect remain questions for future research. PMID- 3095133 TI - Teratogenic effects of cadmium on Bufo arenarum during gastrulation. AB - Developing Bufo arenarum embryos were treated during gastrulation with cadmium chloride in concentrations ranging from 6x10(-7) to 1.5x10(-5)M Cd++ at 20 and 30 degrees C. Initial failures at gastrulation result mainly in axial incurvations, microcephaly, hydropsy and abnormal tail formation. The higher temperature has a dual effect: at high concentrations of Cd early malformations are significantly increased; whereas, at low concentrations the higher temperature prevents alterations. PMID- 3095134 TI - Characterization of amyloid protein from mice infected with alveolar hydatid cyst: isolation, purification, and amino acid composition. AB - The physicochemical properties of alveolar hydatid cyst-induced amyloid (AHCA) were investigated. The AHCA was extracted from spleens, livers, and kidneys of C57BL/6J mice at 12 weeks postinfection and purified on Sephadex G-100 and G-50 gel columns. By using SDS-PAGE and isoelectric focusing techniques the purified AHCA protein showed a molecular weight (MW) of approximately 8,700 and a pI value of 5.3, respectively. The azocasein-induced AA amyloid from C57BL/6J mice had a similar MW but a pI value of 5.8. Unlike mouse AA amyloid, the AHCA was resistant to KMnO4-trypsin treatment, and was shown to cross-react with antisera raised against mouse AA amyloid. The immunologic cross-reactivity between mouse AA, serum amyloid A protein, and AHCA as determined by immunoperoxidase, indirect immunofluorescence, and gel diffusion tests indicated antigenic similarity between AHCA and mouse AA. The amino acid composition of purified AHCA presented both similarities and differences when compared with published data from mouse AA and spontaneously developed mouse amyloid proteins. We report here for the first time the presence of small amounts of methylated basic amino acids and amino sugars in AHCA protein. PMID- 3095135 TI - Penicillinase producing Neisseria gonorrhoeae in the United Kingdom. AB - Following the isolation of the first penicillinase-producing gonococcus in 1976 the number of such isolates rose rapidly in the United Kingdom until 1982. There was a smaller increase in 1983. At St. Thomas' Hospital, the largest clinic serving the population of South London, there was a parallel rise with stabilisation from 1982 to 1984. While for some years relatively more infections diagnosed at St Thomas' Hospital appeared to originate abroad than in the country as a whole, this proportion has gradually declined to approximately the national figure. With a gradual decline in the total numbers of gonococcal infections in the United Kingdom the proportion of infections by PPNG has continued to rise. It is important to monitor this closely, to review therapy recommendations where indicated and to maintain a vigilant watch for local epidemics. PMID- 3095136 TI - Demographic and socio-economic patterns of hospitalization for infectious diseases in Israel. AB - Hospitalization rates in Israel for five common enteric communicable diseases were computed according to age, sex, religion, origin and place of residence. Higher rates were found for non-Jews of both sexes and males of all origins. Higher rates were also found for settlements inhabited by new immigrants of low socio-economic classes. These findings suggest that more emphasis should be placed upon sanitary improvements and education for better health, rather than on merely improving the health delivery system. PMID- 3095137 TI - The role of surgery in transmitting "post-transfusion hepatitis". AB - The role of surgery as an additional risk in transmitting "post-transfusion" hepatitis was investigated in a retrospective study on acute hepatitis occurring in 77 transfused patients, 293 transfused and operated patients and 243 hepatitis cases with history of surgery without transfusion. Hepatitis A patients admitted to the same centres in the same period were utilized as controls. In transfused patients the percentage of NANB hepatitis was higher than that of type B (61.0% vs. 36.4%), while in the operated not transfused group the percentage of type B was twice that of type NANB (63.4% vs. 32.5%). In transfused and operated cases intermediate values were observed. The age-adjusted measures of association between exposures and the different hepatitis types showed a lack of effect of transfusion and a dominant role of surgery in transmitting type B hepatitis. In contrast, NANB "post-transfusional" cases were actually a mixture of post transfusional and post-surgical cases, since both these exposures were found to be significantly associated with the disease. Our results suggest that studies on the incidence and the etiology of post-transfusion hepatitis should take into account the risk of surgical exposure which might have occurred. PMID- 3095138 TI - [Determination of diazepam and its metabolites in the blood by microcolumn high performance liquid chromatography]. AB - A rapid, sensitive and specific quantitative method of simultaneous determination of diazepam and its pharmacologically active metabolites in biological fluids by means of high-performance liquid chromatography on a liquid chromatograph "Milichrom" was used for pharmacokinetic studies in the "mother-placenta-fetus" system. PMID- 3095139 TI - [Nitroglycerin pharmacodynamics in myocardial infarct]. AB - The experience of treating 2,500 patients with acute myocardial infarction enabled the authors to prove a diverse character of nitroglycerin effect: it exerts a positive inotropic action on the myocardium, improves elastic properties of the myocardium, normalizes energy balance of the myocardium, influences the system of the blood aggregate state through contractile elements of platelets producing a hypocoagulatory effect. PMID- 3095140 TI - [Characteristics of the action of nitroglycerin on the hemodynamics of patients with ischemic heart disease in relation to the content of SH groups of the blood serum and the tolerance for physical loading]. AB - The authors examined 196 patients who had survived myocardial infarction and 21 persons without signs of myocardial ischemia. Nitroglycerin test with subsequent control of myocardial contractility, hemodynamics and blood serum content of SH groups indicated that the level of SH-groups could serve as a prognostic criterion of efficacy of nitrates (inverse correlation). PMID- 3095141 TI - Meta-vinculin distribution in adult human tissues and cultured cells. AB - Meta-vinculin distribution in adult human tissue was studied by immunoblotting technique. Meta-vinculin was found in smooth (aorta wall and myometrium) and cardiac muscle, rather than in skeletal muscle, liver, kidney and cultured cells macrophages, foreskin fibroblasts, peripheral blood lymphocytes and vascular endothelial cells. In the primary culture of smooth muscle cells from human aorta the meta-vinculin/vinculin ratio was reduced, and on the onset of cell division meta-vinculin could hardly be detected. Subcultured smooth muscle cells from human aorta did not contain meta-vinculin. The data show that the presence of meta-vinculin is characteristic of 'contractile' smooth muscle cells rather than of proliferating in vitro. PMID- 3095142 TI - Possible incorporation of phosphoserine into globin readthrough protein via bovine opal suppressor phosphoseryl-tRNA. AB - Suppressor [32P]phosphoseryl-tRNA, prepared using bovine seryl-tRNA synthetase and ATP:seryl-tRNA phosphotransferase, was mixed with rabbit reticulocyte lysates containing endogenous hemoglobin mRNA having the termination codon UGA (opal). The chromatographic pattern of the lysate on Sephacryl S-200 showed that the radioactivity of [32P]phosphate in the hot trichloroacetic acid-precipitate (phosphoprotein) was eluted at the position between mature hemoglobin and globin subunits. The phosphoprotein, obtained by chromatography on S-200, moved to the position corresponding to that of globin readthrough protein on SDS-PAGE. The analyses of the hydrolyzate of the phosphoprotein showed the presence of phosphoserine in the protein. These results suggest that animal opal suppressor tRNA functions in vitro to transfer phosphoserine to the position of the termination codon UGA (opal) on mRNA. PMID- 3095143 TI - The single proline-glutamine substitution at position 5 enhances the potency of amyloid fibril formation of murine apo A-II. AB - The primary structure of murine apolipoprotein A-II (apo A-II) has been determined. Apo A-II consists of a single polypeptide chain of 78 amino acid residues, of which the amino-terminus is pyrrolidone carboxylic acid. Except for residues 5 and 38, the amino acid sequence is identical to that of murine senile amyloid protein (ASSAM), which has a common antigenicity with apo A-II. Substitution of glutamine (ASSAM) for proline (apo A-II) at position 5 is distinct and may possibly be related to murine senile amyloid-ogenesis. PMID- 3095144 TI - Guanine nucleotide-binding protein in sea urchin eggs serving as the specific substrate of islet-activating protein, pertussis toxin. AB - A GTP-binding protein serving as the specific substrate of islet-activating protein (IAP), pertussis toxin, was partially purified from Lubrol extract of sea urchin egg membranes. The partially purified protein possessed two polypeptides of 39 and 37 kDa; the 39 kDa polypeptide was specifically ADP-ribosylated by IAP and the 37 kDa protein cross-reacted with the antibody prepared against purified beta gamma-subunits of alpha beta gamma-heterotrimeric IAP substrates from rat brain. Incubation of this sea urchin IAP substrate with a non-hydrolyzable GTP analogue resulted in a reduction of the apparent molecular mass on a column of gel filtration as had been the case with purified rat brain IAP substrates, suggesting that the sea urchin IAP substrate was also a heterooligomer dissociable into two polypeptides in the presence of GTP analogues. Thus, the 39 and 37 kDa polypeptides of the sea urchin IAP substrate correspond to the alpha- and beta-subunits, respectively, of mammalian IAP substrates which are involved in the coupling between membrane receptor and effector systems. PMID- 3095145 TI - An ATP-dependent and inositol trisphosphate-sensitive Ca2+ pool linked with microfilaments of the parietal cell. AB - In digitonin-permeabilized parietal cells, myo-inositol 1,4,5-trisphosphate (Ins P3) or Ca2+ ionophore (A23187) increased the cytosolic Ca2+ concentration due to the intracellular Ca2+ release. Addition of ATP decreased the cytosolic Ca2+ concentration due to the rapid Ca2+ re-uptake into the same or similar pool which releases Ca2+ from a non-mitochondrial location (measured by quin2/AM and 45Ca2+). Cytochalasin B failed to increase the cytosolic Ca2+ concentration in response to Ins P3 or A23187 and even failed to decrease the cytosolic Ca2+ concentration in response to ATP. This implies that the ATP-dependent and Ins P3 sensitive Ca2+ pool is linked with the microfilaments of the parietal cell. In intact parietal cells, A23187 increased the amino[14C]pyrine accumulation (an index of acid secretion), that was independent of medium Ca2+. This increase of acid secretion was inhibited by the pretreatment with cytochalasin B. This suggests that medium Ca2+-independent acid secretion (by A23187) is regulated by the microfilaments. Therefore, there is a close relationship between the intracellular Ca2+ metabolism, microfilaments and acid secretion. PMID- 3095146 TI - Purification of two species of exudate cysteine-proteinase inhibitors that are acute-phase reactants in the carrageenin-induced inflammation in rats. AB - Two species of cysteine-proteinase inhibitors (CPIs) have been purified to homogeneity from exudate in the carrageenin-induced inflammation in rats. The exudate CPIs were separated into two forms (named CPI-1 and -2) in affinity chromatography on S-carboxymethyl-papain-Sepharose, the final stage of purification. CPI-1 and -2 gave different mobilities in polyacrylamide gel electrophoresis (PAGE), probably because of different isoelectric points (pI 4.47 for CPI-1 and pI 4.21 for CPI-2). Both CPI-1 and -2 showed immunological identity in double immunodiffusion and same molecular mass of 68 kDa when analysed by SDS PAGE. These results indicate that CPI-1 and -2 are very similar but distinct CPIs. CPI-1 and -2 are acute-phase reactants and probably represent two species of T-kininogens having inhibitory activity toward cysteine proteinases. PMID- 3095147 TI - Beta-subunits of the human liver Gs/Gi signal-transducing proteins and those of bovine retinal rod cell transducin are identical. AB - The complete cDNA encoding the beta-subunit of the human liver signal transducing proteins Gs/Gi (beta G) has been cloned from a lambda gtll library using an oligonucleotide as a screening agent. The cDNA has 3088 nucleotides and an 11 nucleotide poly(A) tail, of which 280 nucleotides constitute the 5'-untranslated region, 1023 form the open reading frame (ORF) and its stop codon, and 1785 are the 3'-untranslated region with two AATAAA cleavage and polyadenylation signals separated by 1467 nucleotides. The ORF codes for a 340 amino acid polypeptide that is identical to that encoded by bovine retinal rod cell cDNA of the beta subunit of transducin. Yet, it does so by using 87 different codons. Curiously, the 280 nucleotide 5' leader sequence obtained starts with an ATG that is part of another ORF encoding a putative peptide X of 75 amino acids (nucleotide 280 to 55). This work proves for the first time that the beta-subunits of all signal transducing G-proteins, including transducin, are the same. PMID- 3095148 TI - Adenine nucleotide compartmentation in foetal rat hepatocytes. Effects of atractyloside, oligomycin, calcium ionophore and adrenergic agonists. AB - In the presence of lactate plus pyruvate, or glucose or alanine as substrates, ATP/ADP ratios in the cytosol were higher than in mitochondria in isolated rat foetal hepatocytes. The cytosolic ATP/ADP ratios were dependent on substrate (lactate + pyruvate greater than glucose greater than alanine). Oleate increased the cytosolic ATP/ADP ratios in the presence of the other substrates studied. Atractyloside decreased the cytosolic ATP/ADP ratios, oligomycin decreasing these values in both compartments. Isoproterenol, phenylephrine and Ca2+ ionophore decreased the cytosolic ATP/ADP ratio, without altering this value in mitochondria. PMID- 3095149 TI - Protease inhibitor controls prophenoloxidase activation in Manduca sexta. AB - Prophenoloxidase from the hemolymph of tobacco hornworm Manduca sexta can be activated by a specific activating enzyme found in the cuticle. Inhibition studies with benzamidine, diisopropyl phosphofluoridate and p-nitrophenyl-p' guanidinobenzoate indicate that the activating enzyme is a trypsin-like serine protease. An endogenous protease inhibitor, isolated from the hemolymph of Manduca larvae, inhibits the prophenoloxidase activation mediated by this enzyme. These results indicate that the probable physiological role of endogenous protease inhibitor is to control the undesired activation of prophenoloxidase in the hemolymph. PMID- 3095150 TI - Design of purine nucleoside phosphorylase inhibitors. AB - Purine nucleoside phosphorylase inhibitors hold promise as specific immunosuppressive, anti-T cell leukemic, and antiuricopoietic agents. The best inhibitors available that are biologically active have Ki values from 10(-6) to 10(-7) M and fall into two categories: noncleavable nucleosides preferably iodinated at the C-5' position and C-8-substituted guanine or acycloguanosines. More potent inhibition is shown by phosphorylated acyclonucleosides that function as multisubstrate analogs, but these compounds are excluded from cells. The X-ray analysis of the human erythrocytic enzyme is beginning to reveal the nature of the active site and to explain the structure-activity relationships that have been established with analog substrates and inhibitors. PMID- 3095152 TI - Diarrhea associated with enteral nutrition. PMID- 3095151 TI - Antigenic, functional, and molecular genetic studies of human natural killer cells and cytotoxic T lymphocytes not restricted by the major histocompatibility complex. AB - Cytotoxicity not restricted by the major histocompatibility complex (MHC) is mediated by two distinct types of lymphocyte: natural killer (NK) cells and non MHC-restricted cytotoxic T lymphocytes (CTL). These two types of cytotoxic lymphocytes can be distinguished by antigenic phenotype, function, and molecular genetic studies. In human peripheral blood, NK cells are identified by expression of the Leu-19 and/or CD16 cell surface antigens, and lack of CD3/T cell antigen receptor (Ti) complex expression (i.e., CD3-,Leu-19+). Peripheral blood non-MHC restricted CTL express both CD3 and Leu-19 (i.e., CD3+, Leu-19+, referred to as Leu-19+ T cells). Both Leu-19+ T cells and NK cells lyse "NK-sensitive" hematopoietic tumor cell targets, such as K562, without deliberate immunization of the host. However, most "NK activity" in peripheral blood is mediated by NK cells, because they are usually more abundant and more efficient cytotoxic effectors than Leu-19+ T cells. The cytolytic activity of both NK cells and Leu 19+ T cells against hematopoietic targets was enhanced by recombinant interleukin 2 (rIL 2). NK cells, but not peripheral blood Leu-19+ T cells, were also capable of lysing solid tumor cell targets after short-term culture in rIL 2. Southern blot analysis of NK cells revealed that both the T cell antigen receptor beta chain genes and the T cell-associated gamma genes were not rearranged, but were in germ-line configuration. These findings indicate that NK cells are distinct in lineage from T lymphocytes and do not use the T cell antigen receptor genes for target recognition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095153 TI - Human polymorphonuclear leukocytes aminopeptidases. AB - In human polymorphonuclear leukocytes a methionine, leucine, arginine, phenylalanine and alanine aminopeptidase activities were detected, both in cytosol and secondary granules. All activities were EDTA sensitive and their pH optima were in the range of pH 6.5 to 8.6. In the cytosol two enzymes could be distinguished, broad substrate specificity aminopeptidase of pH 4.7-4.9 and a chloride dependent arginine aminopeptidase of pI 5.3-5.5. The granules contain aminopeptidase of pI 4.0-4.6 and of pI 9.8-10.2, different from those in the cytosol. Among them broad specificity aminopeptidases and possibly specific methionine and leucine aminopeptidases could be discerned. PMID- 3095154 TI - Detection of inhibitory inactive fraction of alpha-1-antitrypsin in human serum. AB - Pseudomonas aeruginosa elastase is not inhibited by human serum alpha-1 antitrypsin, it damages inhibitory activity of alpha-1-antitrypsin activity instead. A simple method, based on electrophoresis in urea containing polyacrylamide gel, is described for the separation of active part of the inhibitor from that inactivated by the bacterial enzyme. PMID- 3095155 TI - Drugs in dentistry. Chemical sterilizing agents: glutaraldehydes. PMID- 3095156 TI - [The effect of dinitrophenylation on the tyrosinase activity of extracts from human melanomas]. PMID- 3095157 TI - Immunoglobulin levels of the winter flounder (Pseudopleuronectes americanus) and the summer flounder (Paralichthys dentatus) injected with the microsporidan parasite Glugea stephani. AB - The microsporidan parasite G. stephani, has been found in the intestine of the American winter flounder Pseudopleuronectes americanus. A quantitative study of total serum immunoglobulin (Ig) levels has shown that an injection of this parasitic spore causes a decrease in serum IgM levels. The level of suppression seems to be related to the number of spores injected into the host, as well as the frequency of injections administered. As the dosage of spores injected into the winter flounder increased from 3 X 10(3)/ml to 3 X 10(8)/ml, the level of serum IgM's decreased proportionally. When a single IM injection of spores (3 X 10(6)/ml) was administered, the initial decrease in serum IgM was followed by a gradual recovery of total Ig levels by day 60. Repeated injections of G. stephani on days 21 and 42 respectively, causes an even greater decrease in total IgM levels. Indomethacin (a drug that inhibits prostaglandin activity), has been shown to negate the decrease in IgM levels caused by the G. stephani spores. When injected twice weekly, the indomethacin inhibited the decrease in serum IgM caused by the spore homogenate, with IgM levels comparable to those observed in control WF. This supports previous observations, that prostaglandins are implicated in the decrease in IgM levels induced by injection of the parasite. The effects of G. stephani on serum Ig levels does not seem to be species specific. When the spores were injected into summer flounder (Paralichthys dentatus) together with an erythrocyte antigen, horse red blood cells (HRBC), a decrease in total IgM levels occurred, as well as a decrease in hemagglutination titers to HRBC similar to the decrease described in winter flounder. PMID- 3095158 TI - Drosophila blood cell surface changes in response to stimulation by dopamine in vitro. PMID- 3095159 TI - The positive feedback of estradiol on gonadotropin secretion in women with perimenopausal dysfunctional uterine bleeding. AB - The functionality of the hypothalamic-pituitary-ovarian axis was explored in 27 women with perimenopausal dysfunctional uterine bleeding. The positive feedback effect of estradiol on LH and FSH was studied by the estrogen challenge test, which was performed by a single i.m. injection of estradiol benzoate. An early decline of both LH and FSH was followed by an increase of LH, mainly due to the cases in which the estrogen test was positive. FSH remained low through the whole period tested. The results were compared with those found in 5 normal menstruating women. The frequency of positive estrogen tests, defined by an acute estradiol-induced discharge of LH, was lower in the perimenopausal patients (P less than 0.025). The results of the tests used in our study showed an impairment of the positive feedback system in the perimenopausal-dysfunctional-bleeding group. PMID- 3095160 TI - Buccal nitroglycerin in congestive cardiac failure: a multicentre study. AB - One-hundred-and-ninety-two elderly patients with symptoms of congestive cardiac failure, despite therapy with diuretics and inotropic agents, received buccal nitroglycerin as additional medication. They were assessed for up to 6 months. Improvements in symptoms and functional classification were apparent within 14 days, and were maintained for the duration of the study. PMID- 3095161 TI - A Drosophila melanogaster mutant resistant to a chemical analog of juvenile hormone. AB - Methoprene, a chemical analog of juvenile hormone, is toxic when applied to late third-instar larvae of Drosophila melanogaster. Using an ethyl methane sulfonate mutagenesis screen, we have selected two noncomplementing mutants, one of which is nearly 100 times more resistant than wild-type to either methoprene or juvenile hormone III topically applied or incorporated into the diet. The mutation, named methoprene-tolerant (Met), also confers resistance to methoprene induced pseudotumor formation in larvae as well as to juvenile hormone III- or methoprene-induced vitellogenic oocyte development in adult females. Met adults show little or no cross-resistance to four other insecticides. The mutation was mapped by recombination to a location 35.4 on the X-chromosome and uncovered by chromosomes deficient for the region 10C2-10D4. Complementation was observed between Met and a lethal allele of the RNA polymerase II locus, which is also found in this region. Since the Met mutation also confers resistance to methoprene-induced abnormalities in adult cuticle formation, the autonomy of Met expression could be evaluated in flies mosiac for this mutation. Autonomous expression of Met was found both in abdominal cuticle as well as in external male genitalia. The characteristics of Met are consistent with those expected of a mutant having altered juvenile hormone reception in target tissue. PMID- 3095162 TI - Development of an indirect flight muscle in a muscle-specific mutant of Drosophila melanogaster. AB - Stripe (sr) is a highly specific mutant affecting only one of the indirect flight muscles, the dorsal longitudinal muscle (DLM). In the homozygous condition the DLM is reduced in size. In the hemizygous condition (sr/Df(3)sr) no DLM is present in the adult, though all other thoracic muscles are present. In the early stages of pupation, DLM development in sr/Df(3)sr is no different from that in wild type. Adult myocytes collect around target larval muscles and fuse to form myotubes; myofilaments are synthesized. Subsequently (35-hr pupa) the DLM commences to degenerate, forming random clumps of vacuolated muscle tissue. Adjacent muscles are unaffected and develop normally. In the adult a neuroma-like mass of nerve tissue is maintained where the DLM would normally be located. In this mass many abnormal synapses (hemisynapses) are seen: presynaptic specializations occur in the absence of any postsynaptic structure. Small remnants (less than 16-microns diameter) of muscle tissue are sometimes found in the neuroma-like mass. Such remnants resemble slow muscle, not the normal fast type of DLM. These data suggest a possible muscle origin from primary and secondary myotubes. The DLM motor axons are present in the neuroma-like mass, persisting even with the virtual degeneration of their end target. Thus, motoneurons and presynaptic specializations can survive independently of postsynaptic targets. PMID- 3095163 TI - l(1)hopscotch, A larval-pupal zygotic lethal with a specific maternal effect on segmentation in Drosophila. AB - The maternal and zygotic effect phenotypes of mutations at the l(1)hopscotch (l(1)hop) locus are described. l(1)hop is located in 10B6-8 on the salivary gland chromosome map and 17 alleles have been characterized. A complex complementation pattern is observed among the 17 alleles. The lethal phase of null alleles of l(1)hop occurs at the larval-pupal interface associated with a small disc phenotype. Embryos produced from homozygous l(1)hop germline clones show segment specific defects. The extent of these defects depends upon both the strength of the allele and the paternal contribution. In the most extreme case embryos exhibit defects associated with five segments T2, T3, A4, A5, and A8. In the less extreme phenotype defects are only associated with A5. Thus, activity of l(1)hop+ is required both for the maintenance and continued cell division of diploid imaginal precursors and for the establishment of the full array of segments. PMID- 3095164 TI - The effects of aphidicolin on morphogenesis and differentiation in the sea urchin embryo. AB - Aphidicolin, an inhibitor of DNA polymerase alpha, blocks DNA synthesis and cell division in sea urchin embryos. The effects of this inhibition appear to be stage dependent. Blastulae treated with aphidicolin before the thickening of the vegetal plate undergo developmental arrest prior to gastrulation. The extent of inhibition of DNA synthesis varies from 60 to 93% in these embryos. However, when aphidicolin is added after the vegetal plate has thickened, development continues normally through pluteus formation, even though DNA synthesis is inhibited by greater than or equal to 90% and cell division has ceased. These observations indicate that, from the vegetal plate stage onward, morphogenesis and overt differentiation are independent of DNA synthesis and cell division. PMID- 3095165 TI - Reversal of diabetes in outbred mice by islet allotransplantation. AB - The combination of donor pretreatment with cyclophosphamide, organ culture in 95% O2:5% CO2 for 7-10 days, and short-term immunosuppression of recipients with cyclosporin A (CsA) were necessary to obtain 100% survival of single-cluster BALB/c islet allografts in outbred mice. In vivo and in vitro pretreatment of the donor tissue alone resulted in the acceptance of 45% of the islet allografts in nonimmunosuppressed outbred mice. CsA treatment of recipients alone yielded 40% survival of the untreated allografts. CsA treatment played an important role in maintaining the capacity of islet allografts to function in outbred mice. During CsA treatment, 88% of streptozocin-treated mice showed graft-dependent reversal of diabetes; the remainder showed no evidence of graft function, and CsA treatment failed to prevent acute graft rejection. After withdrawal of CsA immunosuppression, 38% of this total group remained normoglycemic. These findings suggest that modulation of both donor-tissue immunogenicity and recipient responsiveness will be required for successful pancreatic islet transplantation in diabetic humans. PMID- 3095166 TI - Lymphoid cell subsets in normal human small intestine. AB - Nineteen specimens of normal tissue were obtained from the duodenum, upper jejunum and terminal ileum. Specimens were fixed with periodate-lysine paraformaldehyde and then frozen sections were made. Lymphoid cell subsets were identified by indirect immunoperoxidase staining using mouse anti-human monoclonal antibodies. RESULTS: There was a remarkable variation in the distribution of positive cells among individuals and even within single sections. Lymphoid cell subsets of the three parts of the small intestine were almost identical except for the difference in IgA subclasses of IgA-containing cells. IgA1 predominated over IgA2 in the jejunum while IgA2 predominated over IgA1 in the ileum. The subsets in the lamina propria (LP) and in the epithelium were clearly distinct; Leu 3+ (helper/inducer T) predominated in LP while Leu 2+ (suppressor/cytotoxic T) predominated in the epithelium and no Ig-containing cells were found in the epithelium. In LP the mean ratio of Leu 1+ (pan T):IgA (IgA1 + IgA2) containing cells: IgM: IgG: IgD: IgE: HNK-1+ was 48.9: 36.6: 9.0: 1.8: 1.0: 0.3: 2.4. The staining patterns of HLA-DR+ and Leu 10+ were similar; dense in the top in LP of the villi. In some individuals the apical portion of epithelial cells was stained by anti-HLA-DR. A few positive cells were observed in only two out of 19 cases by anti IL-2R. PMID- 3095168 TI - Carbon dioxide and room air insufflation of the colon. Effects on colonic blood flow and intraluminal pressure in the dog. AB - The potential advantages of carbon dioxide over room air to insufflate the bowel during colonoscopy include its nonexplosive nature and rapid absorption. To evaluate whether this rapid absorption would minimize any reduction in colonic blood flow resulting from the distention, we measured inferior mesenteric artery flow before, during, and after insufflation of the canine colon with room air and carbon dioxide under conditions of transient and constant elevations of intraluminal pressures. Intraluminal pressures remained elevated for briefer periods after carbon dioxide administration, and blood flow was far less compromised. At lower levels of transient (40 mm Hg) and constant (60 to 70 mm Hg) intraluminal pressure elevation, colonic blood flow was actually increased. Because it is nonexplosive and rapidly absorbable and interferes only minimally with colonic blood flow, carbon dioxide is the preferable agent to use during colonoscopy, especially in patients with suspected or proven colon ischemia in whom prolonged distention and diminished blood flow are to be avoided. PMID- 3095167 TI - Dynamics of hepatic glycosaminoglycan accumulation in murine Schistosoma japonicum infection. AB - Hepatic fibrosis is the major pathologic sequela of schistosomiasis and is comprised of extracellular collagen and proteoglycan macromolecules. Glycosaminoglycans (GAGs), the major constituents of proteoglycan molecules, were studied in mice infected with Schistosoma japonicum. Total GAG content was measured by extraction of uronic acid from murine liver sections and isolated hepatic granulomas during the progression from acute (0-15 wk) to chronic (20-30 wk) infection. Infected livers contained elevated levels of uronic acid throughout infection when compared to noninfected livers. Glycosaminoglycan content was found to peak at a value of 2.5 +/- 0.1 pmol/mg tissue (five times normal value) in acute infection (6-15 wk), a time of increasing hepatic fibrosis. Peak uronic acid content in isolated granulomas was also observed during acute infection with a maximal value of 7.1 +/- 0.9 pmol/mg tissue (9-11 wk). During chronic infection (30 wk), hepatic uronic acid content was reduced by 68% in unfractionated liver tissue and by 49% in isolated granulomas (both p less than 0.05). This modulation in GAG accumulation appeared to result from decreased biosynthesis, inasmuch as during chronic infection GAG biosynthetic rates fell by 42% in liver tissue and 53% in isolated granulomas (both p less than 0.05). In addition to these quantitative changes in GAG metabolism, GAG disaccharides were examined qualitatively by high-pressure liquid chromatography, which resolved nonsulfated, 6-sulfated, and 4-sulfated disaccharides. Few qualitative changes were seen in the GAG profile between normal liver and acutely or chronically infected liver. Both the rapid modulation of GAG accumulation despite ongoing infection and its qualitative makeup differentiate hepatic fibrosis seen in schistosomiasis japonica from that observed in many other forms of fibrotic liver disease. PMID- 3095169 TI - Carbon dioxide-insufflated colonoscopy: an ignored superior technique. AB - Colonoscopy and barium enema are complementary studies in the diagnosis of the cause of lower intestinal bleeding. The air usually insufflated during colonoscopy often makes it impossible to perform a good barium enema on the same day. As a possible solution to this problem, we studied the quality of barium enemas performed immediately following carbon dioxide-insufflated colonoscopy. All 15 patients who underwent unsuccessful total colonoscopies using carbon dioxide insufflation were able to have barium enemas performed the same day in contrast to only one out of 15 patients who had air-insufflated colonoscopy. In a survey of all hospitals in Illinois with 150 beds or more, we found only 15 of 146 hospitals used carbon dioxide for colonoscopy insufflation. We recommend the routine use of carbon dioxide for colonoscopic insufflation not only for greater safety and comfort for the patient, but also for the convenience and cost savings. PMID- 3095170 TI - Simplified endoscopic placement of nasoenteral feeding tubes. AB - A technique for expeditious and safe placement of nasoenteric feeding tubes under direct vision is described. Adult patients undergo feeding tube placement with intravenous sedation and topical anesthesia. Endoscopic tube placement requires an average of 10 min and eliminates many risks associated with blind passage. PMID- 3095171 TI - Percutaneous endoscopic duodenostomy. PMID- 3095172 TI - Who's for CO2? PMID- 3095173 TI - Percutaneous endoscopic gastrojejunostomy: a technique to facilitate passage of the jejunostomy tube. PMID- 3095174 TI - [System of evaluating the effectiveness of various methods of preparing and using anti-rhesus reagents]. PMID- 3095175 TI - Vitellogenesis in the lizard Lacerta vivipara jacquin. I. Purification and partial characterization of plasma vitellogenin. AB - The polypeptide moiety of lizard plasma vitellogenin was reproducibly dissociated and separated by SDS-PAGE into two subunits: Vg alpha 2-2.2 X 10(5) Da and Vg beta 1-1.1 X 10(5) Da. In estrogenized females, active incorporation of inorganic 32P into both vitellogenin chains present in the plasma, and in the culture medium of the liver, was identified following autoradiography of SDS polyacrylamide gels. Lacerta vivipara vitellogenin was isolated from pooled plasma collected from heavily estrogenized males by the two-step precipitation procedure of H. S. Wiley, L. Opresko, and R. A. Wallace, (1980, Anal. Biochem. 97, 145-152), followed by chromatography on DEAE-cellulose. This preparation of L. vivipara vitellogenin was of sufficient purity to generate in rabbits an immune serum which cross-reacted very slightly with plasma free of vitellogenin (rocket immunoelectrophoresis). Using the double immunodiffusion procedure it was shown that the anti-vitellogenin serum recognized identical antigenic determinants in plasma from a vitellogenic female or from estrogenized lizards, and in crude vitellus. The immunodetection of L. vivipara native vitellogenin consistently allowed two circulating forms to be distinguished. After autoradiography of a rocket immunoelectrophoresis plate it was demonstrated that both native forms had incorporated inorganic 32P into the polypeptide moiety and/or the phospholipid moiety. PMID- 3095176 TI - Seasonal changes in testicular size and in plasma follicle-stimulating hormone and prolactin concentrations in thyroidectomized male and thyroidectomized castrated starlings (Sturnus vulgaris). AB - Testicular size and plasma concentrations of FSH and prolactin were measured frequently in thyroidectomized male and thyroidectomized castrated starlings kept in outdoor aviaries during 1 year. In thyroidectomized males, testes increased from minimal to maximal size during March, remained large until June, and then decreased slowly during the next 6 months. Plasma FSH increased to a peak in April (126 micrograms/litre) and then declined slightly. Plasma FSH in thyroidectomized castrates was very high (360-760 micrograms/litre) and did not change significantly during the year. In both groups of birds, plasma prolactin concentration remained low (less than 5 micrograms/litre) and there was no molt. These results demonstrate that while thyroidectomy prevents the onset of photorefractoriness in starlings, short days nevertheless cause gonadal regression. However, this regression is not analogous to the short-day-induced gonadal regression shown by species, such as quail, which do not exhibit absolute photorefractoriness. PMID- 3095177 TI - Improved purification of rat intestinal lactase. AB - A rapid and improved method to obtain purified lactase from rat intestine is described. The purification procedure involved only two chromatographic steps. The degree of purification was far above (500 fold) the values reached with classical methods. Rabbit antisera raised to the purified lactase were characterized using conventional immunological techniques. The specificity of the lactase antibodies was confirmed by the lack of interference on maltase, aminopeptidase and alkaline phosphatase activities measured after papain extraction of the membrane proteins. PMID- 3095178 TI - The number and role of histidine residues in the active site of guanyloribonuclease Sa. AB - The number and role of histidine residues in the active site of extracellular guanyloribonuclease Sa produced by Streptomyces aureofaciens (RNAase Sa) were studied via chemical modification by ethoxyformic anhydride by means of circular dichroism measurements. It was shown that only one of two histidines of RNAase Sa is situated in the active site of the enzyme. Ethoxyformylation of RNAase Sa in the presence of Guo-3'-P, Guo-5'-P and dGuo-5-P, all of them being competitive inhibitors of the enzyme, supported the assumption that an essential histidine residue is bound to the phosphate group in the position 3' of the ribose ring. The circular dichroism measurements of native and modified RNAase Sa and of its complex with Guo-3'-P showed that the modification of the essential histidine residue resulted in alteration of binding of RNAase Sa to Guo-3'-P; histidine thus may play a key role in the formation of such a complex. PMID- 3095179 TI - A rehabilitation of the genetic map of the 84B-D region in Drosophila melanogaster. AB - A reanalysis of the 84B3 to 84D3,5 region of the polytene chromosomes of Drosophila melanogaster has led to the identification and localization of 16 genes. These genes include 11 vital loci, four genes exhibiting nonlethal visible mutant phenotypes and one gene encoding a nonessential enzyme. The identity of the gene products of two of the vital genes has been determined to be alpha tubulin and glucose dehydrogenase (Gld). Three newly identified genes, sticking (stk), half out (hat) and trapped (ted), as well as Gld are required for eclosion. Among the nonessential genes are roughened eye (roe) and ruffed eye (rue), which affect eye texture. The roe phenotype is greatly enhanced by deletions that simultaneously remove roe and an unidentified locus in 84E. Mutations in another nonessential gene, rotund (rn), are characterized by pattern deletions of most adult appendages. PMID- 3095180 TI - Genetic divergence under uniform selection. II. Different responses to selection for knockdown resistance to ethanol among Drosophila melanogaster populations and their replicate lines. AB - We have tested the hypothesis that genetic differences among conspecific populations may result in diverse responses to selection, using natural populations of Drosophila melanogaster. Selection for ethanol tolerance in a tube measuring knockdown resistance was imposed on five West Coast populations. In 24 generations the selected lines increased their mean knockdown times, on average, by a factor of 2.7. An initially weak latitudinal cline was steepened by selection. The two southernmost populations showed the same increases in the selected character, but differed consistently in their correlated responses in characters related to ethanol tolerance. This result indicates that the populations responded to selection by different genetic changes. Selection decreased female body weight and increased resistance to acetone, suggesting components of the response unrelated to ethanol metabolism. The Adhs allele was favored by selection in all populations at the onset, but increased in frequency only in the selected lines of the southernmost population. There was a correlation between latitude and Adh frequency changes, suggesting that fitnesses of the Adh alleles were dependent on the genetic background. Genetic background also had a large effect on the loss of fitness due to selection. Genetic drift between replicate lines caused more variation in selection response than initial genetic differences between populations. This result demonstrates the importance of genetic drift in divergence among natural populations undergoing uniform selection, since the effective population sizes approached those of small natural populations. Drift caused greater divergence between selected replicates than control replicates. Implications of this result for the genetic model of selection response are discussed. PMID- 3095181 TI - Detection of Rsp and modifier variation in the meiotic drive system Segregation distorter (SD) of Drosophila melanogaster. AB - Identification of allelic variability at the two major loci (Sd and Rsp) that interact to cause sperm dysfunction in Segregation distorter (SD) males of D. melanogaster has been hampered by the difficulty in separating the elements recombinationally. In addition, small differences in the strength of Sd alleles or sensitivities of Rsp alleles to Sd are difficult to measure against background genetic or environmental variation. Viability effects of the markers used to score progeny classes may also introduce a bias. Removal of Sd and E(SD) from their second chromosome location to create a Dp(2;Y)Sd E(SD) chromosome eliminates these problems, since any combination of Rsp alleles can be easily tested without resorting to recombinational techniques. Further, since these pairs of Rsp alleles are compared in their response to Dp Sd E(SD) in the same individual males, background variation and viability effects can be easily removed to allow fine-scale resolution of Rsp differences. Tests of all possible pairwise combination of six laboratory chromosomes in this way revealed at least three and possibly four different Rsp allelic classes. In addition, the hierarchical nature of the tests further allowed for determination of the presence of linked suppressors or enhancers of Sd activity. A sample of 11 second chromosomes selected from a group recently isolated from a natural population was also unambiguously ordered as to Rsp allelic status using this approach. The resultant pattern was similar to that obtained for the laboratory chromosomes, except for the not unexpected observation that the natural population apparently harbored more drive suppressors. The pattern of results obtained from these pairwise combinations of Rsp alleles supports the notion that there are no dominance interactions within the group, but that each responds more or less independently to Sd in giving sperm dysfunction. PMID- 3095182 TI - Variation and genomic localization of genes encoding Drosophila melanogaster male accessory gland proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AB - Accessory gland proteins from Drosophila melanogaster males have been separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis into nine major bands. When individual males from 175 strains were examined, considerable polymorphism for nearly one-half of the major protein bands was seen, including null alleles for three bands. Variation was observed not only among long established laboratory strains but also among stocks recently derived from natural populations. There was little difference in the amount of variation between P and M strains, indicating that P element mutagenesis is not a factor producing the variation. Codominant expression of variants for each of five bands was found in heterozygotes, suggesting structural gene variation and not posttranslational modification variation. Stocks carrying electrophoretic variants of four of the major proteins were used to map the presumed structural genes for these proteins; the loci were found to be dispersed on the second chromosome. Since males homozygous for variant proteins were fertile, the polymorphism seems to have little immediate effect on successful sperm transfer. We propose that a high degree of polymorphism can be tolerated because these proteins play a nutritive rather than enzymatic role in Drosophila reproduction. PMID- 3095183 TI - The cuticle proteins of Drosophila melanogaster: genetic localization of a second cluster of third-instar genes. AB - Five third-instar larval cuticle protein genes are placed on the left arm of the third chromosome. For these five genes, 12 variants and two induced mutants are described. All the naturally occurring variants are codominant. One EMS-induced mutant is characterized by the codominant appearance of a new protein, and a second by a recessive mutation that codes for a modifier of third-instar larval cuticle protein 5 (L3CP-5). All but the putative modifier gene map to within less than 0.3 map units of each other on the left arm of the third chromosome at approximately 11. We propose that these genes constitute a cluster of third instar cuticle protein genes. The induced recessive mutant maps outside of the cluster to a region also on the left arm of the third chromosome. The proteins and their genes should prove useful for both developmental and evolutionary studies. PMID- 3095184 TI - One-step and stepwise magnification of a bobbed lethal chromosome in Drosophila melanogaster. AB - Bobbed lethal (bbl) chromosomes carry too few ribosomal genes for homozygous flies to be viable. Reversion of bbl chromosomes to bb or nearly bb+ occurs under magnifying conditions at a low frequency in a single generation. These reversions occur too rapidly to be accounted for by single unequal sister chromatid exchanges and seem unlikely to be due to multiple sister strand exchanges within a given cell lineage. Analysis of several one-step revertants indicates that they are X-Y recombinant chromosomes which probably arise from X-Y recombination at bb. The addition of ribosomal genes from the Y chromosome to the bbl chromosome explains the more rapid reversion of the bbl chromosome than is permitted by single events of unequal sister chromatid exchange. Analysis of stepwise bbl magnified chromosomes, which were selected over a period of 4-9 magnifying generations, shows ribosomal gene patterns that are closely similar to each other. Similarity in rDNA pattern among stepwise magnified products of the same parental chromosome is consistent with reversion by a mechanism of unequal sister strand exchange. PMID- 3095186 TI - DRGs: an overview of the issues. AB - The prospective payment system based on diagnostic related groups adopted by Medicare in 1983 has many deficiencies with respect to psychiatric care. Due to the efforts of the American Psychiatric Association, psychiatric units in general hospitals have been temporarily exempted from this system of per-care payment. A number of problematic issues need to be addressed in the design of any modified or alternative system of financing psychiatric care. These issues include the problems of premature discharge, code manipulation, cost-shifting, and equitable patient access to psychiatric services. The potential effects of a DRG system of payment on clinical practice are reviewed. The reasons for the shortcomings of the DRG system in predicting utilization of services are discussed, and areas for future research are suggested. PMID- 3095185 TI - The organization of genetic variation for recombination in Drosophila melanogaster. AB - The amount and form of natural genetic variation for recombination were studied in six lines for which second chromosomes were extracted from a natural population of Drosophila melanogaster. Multiply marked second, X and third chromosomes were used to score recombination. Recombination in the second chromosomes varied in both amount and distribution. These second chromosomes caused variation in the amount and distribution of crossing over in the X chromosome and also caused variation in the amount, but not the distribution, of crossing over in the third chromosome. The total amount of crossing over on a chromosome varied by 12-14%. One small region varied twofold; other regions varied by 16-38%. Lines with less crossing over on one chromosome generally had less crossing over on other chromosomes, the opposite of the standard interchromosomal effect. These results show that modifiers of recombination can affect more than one chromosome, and that the variation exists for fine-scale response to selection on recombination. PMID- 3095187 TI - [Genetic analysis of Escherichia coli K-12 mutants defective for the structural and regulatory genes for second purine nucleoside phosphorylase]. AB - Two types of mutants lacking the second purine nucleoside phosphorylase (PNPase 2) activity were isolated using the Escherichia coli K-12 pndR strains with constitutive or inosine-inducible synthesis of the PNPase 2. The mutations of the first type are recessive to the pndR+ allele on the F' episome. They are closely linked to the original pndR+ mutations and therefore affect the pndR gene encoding the activator protein. The mutations of the second type affect the PNPase 2 structural gene (pndA) and are recessive to the pndA+ allele on the F' episome. The nupC-pndR-pndA-ptsH-cysA gene order was established by means of four and five-factorial transductional crosses. PMID- 3095188 TI - Nucleotide sequence of the late region of Bacillus subtilis phage PZA, a close relative of phi 29. AB - The 12,200-bp sequence of the late region of bacteriophage PZA was determined. Open reading frames (ORFs) and potential ribosome-binding sites were found in this region and the ORFs were assigned to eleven late genes. A potential bidirectional transcriptional terminator was found and its possible function is discussed. PMID- 3095189 TI - Nucleotide sequence of the right early region of Bacillus subtilis phage PZA completes the 19366-bp sequence of PZA genome. Comparison with the homologous sequence of phage phi 29. AB - We have sequenced the rightmost 2079 bp of the Bacillus subtilis phage PZA genome. This region encompasses the right early region. We compared it with the homologous region of phage phi 29. Six open reading frames (ORFs) were found in this region of PZA and one of them was assigned to gene 17. Analysis of putative ribosome-binding sites and comparison with phi 29 ORFs indicate that at least some of the remaining ORFs could encode proteins. Corresponding genes were not identified so far by genetic methods. Promoter candidates in the right early region of PZA were found and compared to phi 29 promoters. The sequenced region together with previously determined sequences [Paces et al., Gene 38 (1985) 45-56 and 44 (1986) 107-114] completes the entire 19,366-bp sequence of phage PZA genome. PMID- 3095190 TI - Length variation in eukaryotic rRNAs: small subunit rRNAs from the protists Acanthamoeba castellanii and Euglena gracilis. AB - We have sequenced the region of the Acanthamoeba castellanii ribosomal RNA transcription unit which encodes the mature small subunit ribosomal RNA (SSU rRNA). It, like the SSU rRNA coding regions of Euglena gracilis and kinetoplastids, is approx. 30% larger than those reported from other eukaryotes. The extra nucleotides are present in highly variable regions of the rRNA genes. Direct sequence analysis of the corresponding variable regions in the rRNA of A. castellanii and E. gracilis demonstrates that the extra nucleotides are present in the mature rRNA; no post-transcriptional modification of the rRNAs occurs to reduce them to a size more typical of eukaryotes. The extra elements present in the rRNAs of these two organisms are not homologous; they have independent evolutionary origins. PMID- 3095191 TI - The national potential of home equity conversion. PMID- 3095192 TI - The Hawaii geriatric foster care experiment: impact evaluation and cost analysis. PMID- 3095193 TI - Attitudes of long-term care nursing personnel toward the elderly. PMID- 3095194 TI - Natural inhibitors of fibrinolysis. PMID- 3095195 TI - Tissue-type plasminogen activator. Mechanisms of action and thrombolytic properties. PMID- 3095196 TI - The acyl-enzymes and pro-urokinase: promising new thrombolytic agents. PMID- 3095197 TI - [Natural inhibitors of fibrinolysis]. PMID- 3095198 TI - [Tissue plasminogen activator: mechanism of action and thrombolytic properties]. PMID- 3095199 TI - [Acyl enzymes and pro-urokinase: promising new thrombolytic agents]. PMID- 3095202 TI - [Treatment of osseous ruptures of the flexor tendons with resorbable materials]. AB - The avulsion fracture of the extensor tendon is first fixed with two PDS-splints to prevent rotation. Thereafter, the fragment is put on compression by a PDS suture. The treatment is similar to the use of Kirschner wires and a wire tension band. PMID- 3095200 TI - [PDS splint in the treatment of fractures]. AB - Polydioxanon-splints have been used instead of Kirschner-wires in 13 cases for the treatment of fractures of the base or head of phalanges and metacarpals and also, in conjunction with intraosseous suture wires, to stabilize the bones in replantation surgery. PMID- 3095201 TI - [Resorbable PDS splints in fracture stabilization and for arthrodeses of the hand]. AB - Small rods of resorbable Polydioxanon (PDS-splints) are suitable for stabilizing fractures of a phalanx, either near the base or the head, be the fracture transverse or comminuted. Such internal splints are especially useful in replantation of clean amputations. Used in combination with intraosseous wiring, osteosynthesis can be achieved that is stable for exercise in all cases. Another use is in arthrodesis of the distal interphalangeal joints and the metacarpophalangeal joint of the thumb. Disadvantages that accompany Kirschner wire fixation are thus avoided. Case descriptions and results are presented. PMID- 3095203 TI - [Urinary tract involvement in von Recklinghausen's disease]. PMID- 3095205 TI - [Effect of glutaraldehyde on cultured cells--restraining effect on multiplication of L cells]. AB - Glutaraldehyde (GA) was tested for its cytotoxic effect on L cell tissue culture system in comparison with formaldehyde (FA). In the first study, the replanted cells were grown to monolayers on the flattened bases of the culture tubes, and then exposed to the drug. In the second study, the drug was added to the cell suspension just put in the culture tubes. In either case, the cells were kept in contact with the drug at 37 degrees C for 24, 48 or 72 hr, after which time the monolayers were removed and the viable cells in each of the tubes were counted up. The change in the number of viable cells was examined in the various concentrations of the drugs and time intervals of cell-drug contact. Both GA and FA showed relatively slight toxic effect when each concentration was 1 microgram/ml. The cells exposed to 1, 10 micrograms/ml of GA or 1 microgram/ml of FA were able to increase in number, though markedly restrained from their multiplication if compared with the control. GA and FA seriously diminished the viable cells at a concentration of 100 micrograms/ml and 10 micrograms/ml, respectively, and they were so toxic that complete cell death was immediately caused even when the concentration of each drug was at 1000 micrograms/ml. Just replanted cells showed less tolerance to the drug effects than the cells of established monolayers; suppression of cell growth was noted with the concentration of 0.8 microgram/ml and above of either GA or FA, and complete cell death was caused by 58 micrograms/ml of GA and 7.0 micrograms/ml of FA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095204 TI - [Power spectral analysis of tremor induced by TRH and oxotremorine in mice]. AB - Tremor induced by TRH and oxotremorine was recorded by a capacitance transducer, and its intensity and frequency were evaluated using power arrays. In mice treated with TRH (20 mg/kg, i.p.), the latency of tremor was 17.1 +/- 1.7 min (mean +/- S.E.) and the duration was 20.4 +/- 2.2 min, while the frequency was 13.7 +/- 0.3 Hz. In animals with oxotremorine (0.5 mg/kg, i.p.), the latency was 4.3 +/- 0.4 min and the duration was 18 +/- 2.2 min, while the frequency was 12.7 +/- 0.3 Hz. The latter frequency, however, was significantly shifted to a lower frequency as a function of time. In TRH-induced tremor, vertical movements appeared in the same degree as horizontal movements. In oxotremorine-induced tremor, the vertical movements were few, whereas the horizontal movements were observed in a degree similar to those of TRH. The TRH tremor was suppressed by haloperidol and propranolol, but not by atropine. On the contrary, the oxotremorine tremor was inhibited by atropine, but not by haloperidol or propranolol. These results suggest that mechanisms of tremor induced by TRH differ qualitatively from those by oxotremorine; dopaminergic and beta-adrenergic receptor mediated functions may be linked to the developments of tremor caused by TRH, while cholinergic systems have a little effect in mice. The apparatus used in this study and power spectral analysis with power arrays may provide a useful method for simultaneous evaluation of the latency, duration, intensity and frequency of tremors. PMID- 3095207 TI - Benzothiazolium salts--relationships between their structure, toxicity and effect on the plastid system of Euglena gracilis. AB - The effects of 41 benzothiazolium salts on Euglena gracilis were characterized with regard to the influence on growth and on chlorophyll synthesis, and to their ability to induce permanent loss of chloroplasts. Some salts induced white mutants of E. gracilis (the first benzothiazole derivatives with this activity). The relationship between the biological effect and chemical structure was confirmed and expressed quantitatively by means of Free - Wilson and Fujita - Ban analysis. PMID- 3095206 TI - Mechanism of counteraction of aflatoxin toxicity by thymine and folic acid in Bacillus megaterium. AB - Thymine and cytosine as well as the intermediates in pyrimidine biosynthetic pathway dihydroorotic acid, orotic acid, carbamyl aspartate and 5'-uridine monophosphate and folic acid, was synergistic. 2-14C-Thymine, 6-14C-orotic acid and 14C-formate but not 2-14C-uracil, were incorporated into DNA more in the presence of aflatoxin. These findings indicated that aflatoxin inhibited the pyrimidine base synthesis which could be overcome to a great extent by the addition of thymine and folic acid to aflatoxin-treated cells. PMID- 3095208 TI - Microbial production of hydroxy and oxo fatty acids by several microorganisms as a model of adipocere formation. AB - Some varieties of aerobic or anaerobic microorganisms from the human stool and adipocere were separated and identified. These separated microorganisms together with other authentic ones produced 10-hydroxystearic acid from oleic acid. Some bacteria could convert oleic acid to 10-oxostearic acid as well as 10 hydroxystearic acid. These findings indicate that the microbial enzyme(s) catalyzes the hydration of oleic acid and probably the oxidation of this hydrated product. Aerobic bacteria as well as anaerobic microorganisms were found to be involved in the formation of adipocere. PMID- 3095209 TI - [Conjunctival changes in long-term topical drug therapy of glaucoma]. PMID- 3095210 TI - Cytotoxic and DNA-inhibitory effects of iron chelators on human leukaemic cell lines. AB - Cytotoxic and DNA synthesis inhibitory effects of several iron chelators with different physicochemical properties have been tested in four myeloid leukaemic cell lines (U937, K562, ML2 and HL60). The small lipophilic chelators 8 hydroxyquinoline, tropolone and omadine at 2 X 10(-5) M, caused substantial inhibition of labelled leucine and thymidine uptake into cells and also cell death following 4-h incubation. These effects were approximately 10-fold increased when the drugs were pre-incubated with equimolar amounts of iron. Iron alone and hydrophilic chelators e.g. desferrioxamine had insignificant cytotoxic and DNA synthesis inhibitory effects under the same conditions. PMID- 3095213 TI - [A study on quantification of human serum apolipoprotein AI by radial immunodiffusion assay]. PMID- 3095212 TI - Government asks private sector to plug LTC gaps. PMID- 3095211 TI - Expression of the T1 (CD5, p67) surface antigen in B-CLL and B-NHL and its correlation with other B-cell differentiation markers. AB - The T1 surface antigen (CD5,p67) expression on blood lymphocytes (PBL) and lymphoid cells from lymph node biopsies (LN) from 31 patients with B-cell chronic lymphocytic leukemia (B-CLL) and 79 with B non-Hodgkin lymphoma (B-NHL), was detected in 25 B-CLL (80 per cent) and in 11 B-NHL (13 per cent) belonging to the following histologic subtypes: lymphocytic of CLL type (DLWD) one case, lymphoplasmacytoid (DLWD) four cases, centrocytic (DLPD) five cases, immunoblastic (DH) one case. All B-CLL and the T1 + B-NHL were also tested with monoclonal antibodies against the Common Acute Lymphoblastic Leukemia Antigen, B cells (FMC7, FMC8, BA1, Y29-55), T cells (OKT11a), HLA-DR and HLA-DQ monomorphic determinants. All the B-CLL and the T1+ B-NHL were CALLA-, BA1+, Y29.55+. FMC7+ cells were detected in large numbers six B-CLL (three T1+ and three T1-) and in four centrocytic lymphomas. FMC8 reacted with 70 per cent of leukemias (where it stained 30 per cent of neoplastic cells) and with 8/9 T+ B-NHL. HLA-DR and HLA-DQ molecules were detected in 100 per cent and 90 per cent of cases respectively. In vitro treatment of HLA-DQ- or T1- B-CLL with phorbol ester TPA led to the expression of these antigens as well as of the receptors for Interleukin 2 and MLR3 activation antigen. Surface membrane Ig (SIg) was detected in 79 per cent of cases, its density measured by FACS analysis varied, even markedly, from case to case. Among the B-CLL, cells with high SIg content were either T1+ or T1- and more likely FMC7+. The SIg- cases were seven B-CLL (five T1+ and two T1-) and two B-NHL, in which, however, cytoplasmic IgM was detected. This study reveals the existence of four major B-CLL subgroups: T1- SIg-, T1+ SIg+, T1+ SIg+, T1- SIg+. It also indicates that the T1 antigen may be transitionally present during B-cell differentiation and that its expression may precede that of SIg as supported by the in vitro studies. In addition, the finding that some B-NHL are T1+ suggests that they derive similarly to the B-CLL from a common progenitor. PMID- 3095214 TI - Immunophenotypes in "well-differentiated" lymphoproliferative disorders, with emphasis on small lymphocytic lymphoma. AB - The histologic, immunophenotypic, and clinical findings in 24 cases of "well differentiated" lymphoproliferative disorders are presented, with an emphasis on small lymphocytic lymphoma (SLL; well-differentiated lymphocytic lymphoma, WDLL). SLL was diagnosed in 18 patients, Waldenstrom's macroglobulinemia in one, mantle zone lymphoma (MZL) in four, and intermediate differentiated lymphocytic lymphoma (IDL) in one. Immunophenotypic analysis revealed one SLL to be of T-cell derivation, while a monoclonal B-cell phenotype was found in the remaining 23 patients; 20 of these neoplasms co-expressed the pan-T-cell antigen Leu-1. This included three of the four patients with MZL and the patient with IDL. All SLLs with pseudofollicular growth centers stained for transferrin receptor. Additionally, a survey of 248 non-Hodgkin's lymphomas of all types revealed four of 70 patients with B-cell large cell lymphoma (LCL; diffuse histiocytic lymphoma, DHL) that also co-expressed the same Leu-1 antigen. Immunoperoxidase study of both frozen tissue sections and cytocentrifuge preparations eliminated the limitations of faint antigen expression and/or interstitial immunoglobulin staining. In addition to detailing the immunophenotype of SLL, the immunologic kinship of MZL/IDL to SLL and the uncommon co-expression of Leu-1 in B-cell LCLs are demonstrated. PMID- 3095216 TI - Treatment of uncomplicated gonorrhoea with single dose aztreonam. AB - Infection with Neisseria gonorrhoeae was cleared in 61 men and 26 women at all sites (except in the pharynx of one male bisexual patient with urethral and pharyngeal gonorrhoea) after treatment with aztreonam as a single 1 g intramuscular injection. Aztreonam was well tolerated with no adverse effects. This monobactam antibiotic was effective against both penicillin sensitive and resistant strains. PMID- 3095217 TI - Microbiological survey of acute epididymitis. AB - In an 18 month period, 198 men presented with a painful, swollen, and tender epididymis or testicular or scrotal pain. Fifty were excluded from analysis because of prior antibiotic treatment or a history of the disease, or both. Of the remaining patients, epididymitis was not diagnosed in 108, though 23 (21%) of them had urethritis. Thus 40 men were seen who had acute unilateral epididymitis. Of the 27 less than 35 years old, 13 (48%) had a urethral chlamydial infection and two others a gonococcal infection. Sexually transmitted micro-organisms were not confined, however, to the younger age group, though only two (15%) of 13 men who were 35 years or older had a urethral chlamydial infection. Most, that is 29 (73%), of the patients with acute epididymitis also had urethritis when first seen. Urethral micro-organisms were found most often in 13 men who had severe epididymitis, chlamydial infection occurring in eight (62%) of the patients in this category. PMID- 3095215 TI - Penicillinase producing gonococci: a spent force? AB - Though the incidence of gonorrhoea caused by penicillinase producing Neisseria gonorrhoeae (PPNG) strains at St Mary's Hospital rose rapidly from 1980 to reach 6.2% in 1982, it declined in 1983 (8.6%) and in 1984 (6.5%), a trend that has continued in 1985. The use of penicillinase stable antibiotics or more effective contact tracing are unlikely to be responsible for this recent decline. We have always isolated very few PPNG strains from homosexual men, and the possible effects of the acquired immune deficiency syndrome (AIDS) on sexual behaviour in this group is therefore unlikely to be relevant. We have seen a steady increase in the proportion of PPNG strains carrying the 4.4 megadalton penicillinase plasmid (67% of PPNG strains in 1984). Strains carrying both the 4.4 megadalton plasmid and the 24.5 megadalton conjugal plasmid were very common in 1982, but since then have declined in importance. PPNG strains carrying the 3.2 megadalton plasmid have become less common, and the presence of the 24.5 megadalton plasmid in these strains has not apparently led to their wider dissemination in the community. Whereas the basic pattern of PPNG auxotypes has changed little, since 1982 we have isolated an increasing number of mixed auxotypes with nutritional requirements other than just proline. PPNG strains carrying the 4.4 megadalton plasmid seem to be more resistant to erythromycin, tetracycline, and streptomycin than those carrying the 3.2 megadalton plasmid. Spectinomycin resistance has only occurred in strains carrying the 4.4 megadalton plasmid. PMID- 3095218 TI - Infection of a surgical wound by beta lactamase producing Neisseria gonorrhoeae. PMID- 3095219 TI - Asthma and rhinitis after exposure to glutaraldehyde in endoscopy units. AB - Four nurses working in endoscopy units complained of respiratory symptoms on exposure to alkaline glutaraldehyde used as a disinfectant for fibre-optic endoscopes. A provocation test was positive in two of these patients. This is the first report to use provocation testing to confirm a relation between exposure to alkaline glutaraldehyde and respiratory disease. PMID- 3095220 TI - Comparison of effects of lysine aspirin, soluble aspirin and conventional aspirin on buccal potential difference in healthy volunteer subjects. AB - The effects of aspirin, soluble aspirin and lysine aspirin on buccal mucosal potential difference (p.d.) were compared in a double-blind trial. Placebo and three doses of each preparation containing 150, 300 and 600 mg of aspirin were allocated according to a latin square design. Six volunteer subjects were studied; each received a total of 10 treatments at least 24 h apart. All doses of each preparation considered, a significant treatment effect was seen [F (d.f. = 2,306) = 6.2, P less than 0.003]. Lysine aspirin showed the least effect of the active treatments on buccal p.d. with a change from baseline of +8.5 mV compared with +13.3 for soluble aspirin +14.4 for conventional aspirin and -5.2 mV for placebo. PMID- 3095221 TI - A sudden death due to tocainide overdose. AB - The details of a fatal self-poisoning with the anti-arrhythmic drug tocainide are described. The authors are unaware of another such case. The physiological and toxicological results are post mortem are presented and discussed, with emphasis on the method of analysis of the drug in the body fluids and tissues. Stomach content was analysed by direct solvent extraction followed by ultraviolet spectrophotometry and thin-layer chromatography. Blood, urine and liver concentrations were obtained by high-pressure liquid chromatography, blood and liver samples being extracted under basic conditions and urine analysed directly. Two methods are compared for the liver analysis; an alkaline extraction of an enzymic digestion yielded lower levels of drug than did a mechanical maceration followed by alkaline extraction and 'salting out'. The latter is an adaptation of the method used for analysis of blood. Details of therapeutic and toxic blood/plasma concentrations are taken from the literature and compared with the analytical data, leading to the conclusion that the only logical cause of death was tocainide poisoning. PMID- 3095222 TI - Changes in net CO2 assimilation in wheat seedlings grown in presence of BASF 13.338 (4-chloro-5-dimethylamino-2-phenyl-3-(2H)pyridazinone). PMID- 3095223 TI - Effect of phagocytosis on sialidase activity of normal and diabetic polymorphonuclear leukocytes. PMID- 3095225 TI - Human monocytes tumoricidal activity: the role of interferon-gamma and bacterial lipopolysaccharide in its stimulation, preservation and decay. AB - The effect of interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS) on the cytotoxic activity of cultured monocytes was studied in a 6-h51Cr release assay with Actinomycin-D-treated tumor cells as targets. In this system, the lysis of target cells is mediated by a soluble factor (CF) which is similar or identical to human tumor necrosis factor (TNF). The spontaneous cytotoxic activity of freshly isolated monocytes declined after their maturation to macrophages during in vitro culturing. The decrease in the ability of cultured monocytes to lyse the targets is explained by a decrease in their ability to produce the soluble cytolytic factor. Both LPS and IFN-gamma modulated the effect of culturing. LPS exhibited a dual effect. Within 2-3 h after its addition, LPS enhanced the cytotoxic activity of monocytes by increasing the synthesis of CF. However, upon a longer incubation, the decay of the activity was more pronounced in the presence of LPS. IFN-gamma did not augment the cytotoxic activity of monocytes above the basal level, yet it prevented the loss of activity which accompanies the process of monocyte maturation to macrophages. PMID- 3095224 TI - Immuno- and histochemical studies on galactan and human blood group-related receptors in the bovine lung. AB - Using a monoclonal anti-galactan antibody and streptococcus B type II antibody, the distribution of lung galactan could be demonstrated for the first time in a vertebrate organ. In addition to the immunochemical demonstration of the bovine lung galactan, a human blood group A-like glycoprotein is detectable by lectinological methods in the bovine lung tissue. Various other lectin-receptors, for instance those of the peanut lectin (PNA) or for lectins with L-fucose (UEA) and N-acetyl-lactosamine (ECA) specificity show a typical staining pattern in bovine lung. PMID- 3095226 TI - Delineation of two defects responsible for T-cell hyporesponsiveness to concanavalin A in MRL congenic mice. AB - MRL-lpr mice and their congenic counterparts MRL-+ spontaneously develop an autoimmune disease that resembles systemic lupus erythematosus in humans. The two strains, although congenic, differ by a considerable number of disease parameters, reflecting the expression of the lpr autosomal recessive gene. One paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigated a possible lpr gene-encoded macrophage defect in these mice. It was found, however, that both the MRL-+ and MRL-lpr mice failed to divide in response to Con A, the lack of division correlating with an inability to secrete the growth promoter interleukin-2. In MRL-+ mice and young MRL-lpr mice this non-responsiveness was corrected by the addition of normal CBA PEC. The defect could not be explained by a failure of MRL-+ or MRL-lpr peritoneal exudate cells to quantitatively or qualitatively provide a source of interleukin-1 to Con A-activated T cells or by the possibility that the peritoneal exudate cells were blocked in their function by the presence of sera-derived autoantibodies and/or immune complexes on their membranes. We postulate that the inability of T cells to proliferate in MRL congenic mice can be explained by two defects: the failure of antigen-presenting cells in MRL-+ and MRL-lpr to provide the necessary signals to immunocompetent T cells, this defect not being associated with the lpr gene, and the lpr gene controlled outgrowth of a unique T-cell population that cannot respond in our assay system. PMID- 3095227 TI - Numbers and phenotype of lymphocytes emigrating from sheep bone marrow after in situ labelling with fluorescein isothiocyanate. AB - In normal young lambs the bone marrow was selectively labelled with fluorescein isothiocyanate by a temporary perfusion of one hind-leg. One day later, the incidence of bone marrow emigrants in different lymph nodes, spleen, Peyer's patches, thymus, non-perfused bone marrow and blood was determined. The emigrants were also phenotyped by the use of monoclonal antibodies and classified into monocytes or lymphocyte subsets. Large numbers of lymphocytes left the bone marrow of the perfused leg during 1 day. Considerable numbers of cells migrated to other bone marrow compartments. Varying numbers of mononuclear emigrants were found in peripheral lymphoid organs, with labelling indices ranging from 1.06% in the blood to 0.004% in the thymus. In the spleen, comparable numbers of B- and T lymphocyte emigrants from the bone marrow were found, whereas in the blood, lymph nodes and jejunal Peyer's patches many more emigrants were T lymphocytes than B lymphocytes. In the prescapular lymph nodes, for instance, 90.4% of emigrants were T cells but only 9.6% were B cells. Based on the large numbers of lymphocytes emigrating from the bone marrow, their phenotypes and their entry into other bone marrow compartments, it it can be concluded that the bone marrow of young lambs is an integral part of the migratory route of lymphocytes. PMID- 3095228 TI - Monoclonal antibodies against the flagellar fraction of epimastigotes of Trypanosoma cruzi: complement-mediated lytic activity against trypomastigotes and passive immunoprotection in mice. AB - Trypanosoma cruzi, the causative agent of Chagas' disease, is widely spread in Central and South America. The present report describes three monoclonal antibodies (mAbs) directed against the flagellar fraction of epimastigotes (Ffe) of the parasite, Tulahuen strain. The three mAbs were of IgG1 isotype. Indirect immunofluorescence assays revealed that the three mAbs bind to epimastigotes, the FCH-F8-1 and -3 bind to blood trypomastigotes (BT) and FCH-F8-1 is the only one that binds to amastigotes. Three different proteins of the parasite were recognized by the mAbs in immunoprecipitation assays: an 85 kDa of BT with the FCH-F8-1 mAb, a 40 kDa of Ffe with the FCH-F8-2 mAb, and a 90 kDa of Ffe and of BT with the FCH-F8-3 mAb. Positive complement mediated lysis (CML) of BT and metacyclic forms, obtained from the insect vector feces, were shown by the FCH-F8 1, while FCH-F8-3 only showed CML against the metacyclic trypomastigotes. FCH-F8 2 did not mediate any CML activity. Passive transference of the mAbs to BALB/c mice conferred protection, in terms of survival, ranging from 50 (FCH-F8-2 and 3) to 80% (FCH-F8-1) against a challenge with 1 X 10(3) BT. These results suggest that FCH-F8-1 may be a useful tool to purify proteins in order to investigate their role in immunoprotection experiments. PMID- 3095229 TI - Elevated titers of cell-free interleukin-2 receptor in serum and cerebrospinal fluid specimens of patients with acquired immunodeficiency syndrome. AB - A sensitive monoclonal antibody based ELISA was used to detect cell-free interleukin-2 receptor (IL-2R) in the body fluids of patients with acquired immune deficiency syndrome (AIDS), a variety of other disease conditions and a control group of apparently healthy (heterosexual and homosexual) males. Two of the 25 control donors showed low titers (1:8) of IL-2 receptor in the serum samples; the cerebrospinal fluid (CSF) specimens from these individuals proved negative. However, serum and CSF specimens from all the 9 patients with AIDS showed significantly elevated titers (range 1:128 to 1:4096) of IL-2 receptor. The presence of moderate titers (range 1:128 to 1:512) of circulating IL-2 receptor could also be detected in all of the 4 patients with acute lymphocytic leukemia. IL-2 receptor was detectable in the CSF and/or serum specimens from 3 of 3 patients with lung cancer, 3 of 4 patients with acute hepatitis B infection, and 2 of 3 patients with multiple sclerosis. IL-2 receptor could not be detected in the serum or CSF specimens originating from patients with legionellosis (3/3), asthma (3/3), or those with non-pulmonary febrile bacterial infections (4/4). It is concluded that soluble IL-2 receptor may be found in serum or CSF specimens from patients with certain (but not all) disease conditions including AIDS. The conspicuously elevated titers of cell-free IL-2R in the body fluids of patients with AIDS may contribute to the drastic impairment of the immune system regulation observed in such patients. PMID- 3095230 TI - Essential fatty acid deficiency in rats: effects on arachidonate metabolism, generation of cyclooxygenase products and functional responses in neutrophils. AB - Linoleic and arachidonic acid concentrations in neutrophils from rats maintained on a diet with only 0.3% of the energy content as essential fatty acid (EFA, EFAD group) were reduced by 70 +/- 2.2% and 34.8 +/- 5.2%, respectively, compared with controls fed a diet with a normal 3% EFA content. Neutrophil chemiluminescence and aggregation induced by f-Met-Leu-Phe was substantially reduced in the EFAD group. Production of 6-keto-prostaglandin F1 alpha and thromboxane B2 were significantly lower in the EFAD neutrophils when stimulated by the ionophore A23187, whereas there was no difference when leukotriene B4 was used as stimulus. PMID- 3095231 TI - The influence of interferon-gamma and various phagocytic stimuli on the expression of MHC-class II antigens on human monocytes--relation to the generation of reactive oxygen intermediates. AB - Human monocytes show a dose-dependent decrease of the MHC-class II antigen expression (HLA-DR and HLA-DQ) after addition of zymosan or Staphylococcus aureus Cowan I particles. Interferon-gamma did not prevent this process. The expression of MHC-class I antigens was not affected. The dose-response and kinetic curves showed individual differences. An association between the capacity to form reactive oxygen intermediates and the downregulation of MHC-class II antigen expression was observed. In addition, after digestion of the phagocytosed particles interferon-gamma could restore the MHC-class II antigen expression on the cultured monocytes. The possible biological significance of these interactions between interferon-gamma and phagocytosis for the function of monocytes/macrophages in the local inflammatory process is discussed. PMID- 3095232 TI - Both Fc alpha domains of human IgA are involved in in vitro interaction between secretory component and dimeric IgA. AB - The sites of interaction between 125I labelled human secretory component (SC) and dimeric IgA were located by studying the inhibitory effect of various antibodies to IgA. Several Fab' fragments were isolated from three sera of hyperimmunized rabbits. The specificity of these different antibody preparations, as determined by a RIA inhibition test or by ELISA, showed that two were directed against both domains of Fc alpha, two against C alpha 2, two against C alpha 3 and one against Fd alpha. A monoclonal antibody against C alpha 3 was also used. The results indicate that both the C alpha 2 and C alpha 3 domains are equally and independently involved in the interaction between SC and dimeric IgA. PMID- 3095233 TI - Effect of enfenamic acid on prostaglandin synthesis. PMID- 3095234 TI - Fractures caused by epileptic seizures and epileptic osteomalacia. AB - A case of several severe fractures in one patient following epileptic seizures is reported. The patient suffered from epileptic osteomalacia and responded well to vitamin D treatment. The cause of anticonvulsant-induced osteomalacia and its treatment are discussed. PMID- 3095235 TI - Cast-brace treatment of ankle sprains. AB - Forty-two severely sprained ankles treated by a cast-brace have been reviewed. This method was devised to avoid the disadvantages of immobilization. Diagnosis was based on the history and clinical signs. Strain films were taken in 31 patients but it is submitted that this investigation may be misleading unless general anaesthesia is used. The results of the treatment by cast-brace compare favourably with those by other methods and it is considered that patients were able to return to sport in a shorter time. PMID- 3095236 TI - Effect of simulated joint effusion on subchondral haemodynamics and metabolism. AB - The purpose of the present study was to investigate the effect of simulated joint effusion on pO2, pCO2, the regional blood flow and intraosseous bone marrow pressure in the subchondral bone of rabbit. Mass spectrometry was used for simultaneous and continuous registration of subchondral pO2 and pCO2, while the relative argon signal was used for qualitative estimation of regional bone blood flow. The bone marrow pressure was recorded continuously by pressure transducers. Isotonic sodium chloride infusion at a constant pressure of 75 mmHg into the knee joint cavity constituted the basis for joint effusion. An instant increase in the subchondral bone marrow pressure followed the joint effusion (P less than 0.001). This resulted in a significant (P less than 0.01) decrease in the qualitative bone blood flow, significant (P less than 0.01) hypoxia and significant (P less than 0.01) hypercapnia in the subchondral bone. Joint effusion always lasted 30 minutes. Following its release all changes were reversed to normal values within 15 minutes. Within the period of observation no nervous or humoral factors seem to be brought into action. It was concluded that regional venous stasis was responsible for all changes, and that joint effusion should not be left untreated for long periods. PMID- 3095237 TI - Function and antigen recognition pattern of L3T4+ T-cell clones from Mycobacterium tuberculosis-immune mice. AB - T-cell clones were established from Mycobacterium tuberculosis-immunized mice. These clones had the phenotype Thy-1+ L3T4+ Lyt-2- and were restricted by the H 2I-A locus. After antigen stimulation, the T-cell clones secreted interleukin-2 and gamma interferon. Factors produced by these T-cell clones activated normal bone marrow macrophages for antimycobacterial activity in vitro. Furthermore, the T-cell clones could adoptively confer delayed-type hypersensitivity on normal recipient mice. These findings indicate that the T-cell clones clones expressed relevant functions of antimycobacterial immunity. The antigen reactivity of the T cell clones to different mycobacterial species ranged from broad cross-reactivity to stringent specificity, and none of the clones distinguished between M. tuberculosis and M. bovis. Thus, M. tuberculosis-immune helper/inducer T cells of identical phenotype, genetic restriction, and function varied in their antigen specificity. T-cell clones of the type described will facilitate functional characterization of mycobacterial antigens on the T-cell level. PMID- 3095239 TI - Immunogenic activity of gonococcal protein I in mice with three different lipoidal adjuvants delivered in liposomes and in complexes. AB - For several reasons the major outer membrane protein from Neisseria gonorrhoeae (gonococcal protein [PI]) is an attractive component for a gonococcal vaccine. This paper describes the influence of two different physical forms of PI on its immunogenic activity. To this end PI was delivered in liposomes and in protein detergent complexes. In both forms PI was present in a multimeric form. The liposomes were composed of phosphatidylcholine and cholesterol. The effect of dicetylphosphate as a negatively charged amphiphile and three lipoidal adjuvants was investigated. Two lipoidal adjuvants (Avridine and dimethyldioctadecylammoniumbromide) were positively charged amphiphiles, whereas the third one (tridecyl N-acetylmuramyl-L-alanyl-D-isoglutaminate) was neutral. The protein-detergent complexes were also tested in the presence of the lipoidal adjuvants and in an AlPO4-adsorbed form. The liposome preparations were characterized for their size, charge, and residual amount of detergent. The immunogenic activity of PI in all forms was tested in mice. The results of the antibody assays showed that PI in the liposomes was more immunogenic than PI in the complexes. A second dose with liposomes induced only a small booster effect, whereas such a dose with the complexes produced pronounced booster effects. The incorporation of the positively charged lipoidal adjuvants in the liposomes resulted in enhanced booster effects. The highest immunogenic activity of PI after two injections, however, was observed in the complexed form adsorbed to AlPO4. PMID- 3095240 TI - Immunogenic properties of Klebsiella pneumoniae type 2 capsular polysaccharide. AB - The immunoprotective activity of Klebsiella pneumoniae K2 cell surface preparations and purified capsular polysaccharide was tested in mice. The 50% protective dose (PD50), expressed as capsular polysaccharide content, was 2 ng for cell surface preparations and 50 ng for purified capsular polysaccharide. Both preparations lost their immunoprotective activity after alkali treatment. Immune sera were raised in rabbits immunized with cell surface preparations. The precipitating and hemagglutinating capacity of these antisera was tested against either purified capsular polysaccharide or alkali-treated capsular polysaccharide. No difference was observed between the reactivity of the antisera against each antigen. The protective activity of these sera was tested on mice in passive transfer experiments, before and after absorption with either purified capsular polysaccharide or alkali-treated capsular polysaccharide. The sera lost their protective activity after absorption with purified capsular polysaccharide and after absorption with alkali-treated capsular polysaccharide. These experiments show that the difference in immunoprotective activity of cell surface preparations, purified capsular polysaccharide, and alkali-treated capsular polysaccharide is not due to a difference in their antigenic determinants. Cell surface preparations and purified capsular polysaccharide were fractionated by gel filtration on Sepharose 4B and by ultracentrifugation on cesium chloride density gradients. Three forms of capsular polysaccharide have been characterized. (i) A form of capsular polysaccharide with a very high protective activity (PD50 = 2 ng) that copurified with protein and lipopolysaccharide and was characterized by a low coefficient of distribution (Kd = 0.20) and a low density (1.5 to 1.6 g/cm3). (ii) A form of capsular polysaccharide with an intermediate protective activity (PD50 = 50 ng), contamined by less than 3% protein and 1% lipopolysaccharide, with a Kd of 0.35, and a density of 1.7 to 1.8 g/cm3. (iii) A nonimmunoprotective capsular polysaccharide obtained after alkali treatment of either cell surface preparations or purified capsular polysaccharide. The Kd of these fractions varied from 0.20 to 0.90 and their density from 1.7 to 1.8 g/cm3. PMID- 3095238 TI - Analysis of macrophage bactericidal function in genetically resistant and susceptible mice by using the temperature-sensitive mutant of Listeria monocytogenes. AB - Innate resistance to infection by Listeria monocytogenes is genetically controlled and is critically dependent on prompt macrophage recruitment to the sites of infection. Experiments reported here were designed to examine whether there was an additional, qualitative difference between the intrinsic bactericidal activity of the inflammatory macrophages of genetically resistant (C57BL/6J) and susceptible (A/J) hosts. To critically evaluate the bactericidal (rather than bacteriostatic) function of the macrophage, a temperature-sensitive (ts) mutant of L. monocytogenes was developed. Mutagenesis was induced with nitrosoguanidine, and the ts mutants were isolated following enrichment with penicillin-gentamicin combinations. The ts mutants were found to carry the cell surface and biochemical characteristics of the original wild-type strain of L. monocytogenes. Inflammatory peritoneal macrophages from resistant C57BL/6J mice were found to have enhanced listericidal activity when compared with inflammatory macrophages from susceptible A/J mice. However, further analysis of the macrophage populations revealed that this seemingly qualitative advantage was due to the relatively greater proportion of inflammatory macrophages present in the inflammatory exudates of resistant C57BL/6J mice. When homogeneous populations of pure inflammatory macrophages were compared, no interstrain differences in their listericidal activity in vitro were seen. These results suggest that the susceptibility of A/J strain mice to L. monocytogenes is not due to an intrinsic deficiency of the listericidal activity of the inflammatory macrophage. The slight increase in bactericidal activity of macrophages from resistant mice that was reported by others (C. J. Czuprynski, B. P. Canono, P. M. Henson, and P. A. Campbell, Immunology 55:511-518, 1985) is caused by the difference in the relative percentage of resident cells present in the peritoneal exudates from resistant and susceptible mice. PMID- 3095241 TI - Disruption of respiratory cilia by proteases including those of Pseudomonas aeruginosa. AB - Pseudomonad proteases disrupted the function and structure of demembranated cilia (axonemes) extracted from porcine tracheae. Proteolytic degradation by the two pseudomonad proteases elastase and alkaline protease and by trypsin and subtilisin impaired motility of ATP-activated axonemes. In addition, electron microscopic observation of negatively stained axonemes indicated that exposure to proteases caused dissociation into individual doublet or singlet microtubules. Inhibition of motility and axonemal fraying occurred when axonemes were treated with less than 5 U of proteolytic activity of any of the four proteases tested. When the effects of 2 U of each protease were compared, trypsin and subtilisin were able to produce immotility in less time than pseudomonad elastase and alkaline protease, while alkaline protease and subtilisin caused the most axonemal fraying in 10 min. Proteolytic digestion of axonemal proteins was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. All four proteases cleaved dynein proteins (proteins necessary for motility), though treatment with trypsin resulted in the most extensive solubilization of axonemal proteins. Trypsin and subtilisin both produced more changes in the protein profiles of treated axonemes, using fewer units of proteolytic activity, than the pseudomonad proteases. However, the limited alteration of only a few axonemal proteins by pseudomonad proteases indicates that cleavage need not be extensive to produce dysfunction. Thus, ciliary axonemes are susceptible to proteolytic attack. Degradation of axonemal proteins by pseudomonad proteases, which are released during active infection, may contribute to the impaired ciliary function associated with pseudomonad colonization of the respiratory tract. PMID- 3095242 TI - Evidence for N-terminal exposure of the protein IA subclass of Neisseria gonorrhoeae protein I. AB - The JS3 and FA638 strains of Neisseria gonorrhoeae bear a protein IA subclass of protein I (P.I). The purified P.Is of surface-labeled strains JS3 and FA638 were cleaved with the N-terminal degradation enzyme leucine amino peptidase (LAP), and the resultant fragments were separated in sodium dodecyl sulfate-polyacrylamide gels. Autoradiography demonstrated that the surface radiolabel was absent in a LAP-generated P.I peptide that was about 1,900 daltons lower in apparent molecular mass than the native P.I in both strains. Moreover, the 4G5 monoclonal epitope, known to be located on the surface of the organism, was also absent in the LAP-generated P.I peptide that was about 1,900 daltons less in apparent molecular mass than the original P.I of strain FA638. These data strongly suggest that the N terminus of the P.IA subclass is exposed on the surface of the bacterium and that this region represents about 5%, or 15 to 20 amino acids, of the total protein. PMID- 3095243 TI - Rabbit antibodies to the cell wall polysaccharide of Streptococcus pneumoniae fail to protect mice from lethal challenge with encapsulated pneumococci. AB - A conjugate, composed of the cell wall polysaccharide (C polysaccharide) of Streptococcus pneumoniae and bovine serum albumin (BSA), was prepared with the bifunctional agent N-succinimidyl-3-(2-pyridyldithio)-propionate. Analysis with monoclonal antibodies provided evidence that the phosphocholine (PC) moiety of the C polysaccharide was retained during the conjugation procedure. The C polysaccharide-BSA conjugate elicited antibodies to C polysaccharide in rabbits; no PC-specific antibodies were detected in globulins prepared from these hyperimmune sera obtained early and late after a second immunization. Rabbit hyperimmune sera were taken after multiple intravenous injections of the pneumococcus strain SRC-2, which has a capsulelike structure composed of the C polysaccharide. Globulin prepared from these antisera had both C polysaccharide- and PC-specific antibodies. Antibodies to C polysaccharide elicited by the C polysaccharide-BSA conjugate failed to protect mice against intraperitoneal challenge with a strain of type 3 or type 6A pneumococci. The anti-SRC-2 globulin conferred protection against both of these pneumococcal strains. Absorption of the SRC-2 globulin with C polysaccharide, however, failed to change its protective activity. These data provide evidence that antibodies to the C polysaccharide do not confer immunity against infection of mice with encapsulated pneumococci inoculated by the intraperitoneal route. PMID- 3095244 TI - Inhibition of immediate and Arthus responses to schistosome egg antigens by T cells from Schistosoma japonicum-infected mice. AB - Schistosoma japonicum-infected mice develop hepatic granulomas, immediate hypersensitivity (IH), and delayed hypersensitivity (DH) to soluble egg antigens (SEA) released by parasite eggs trapped in liver sinusoids. All of these responses spontaneously regress after 7 to 9 weeks of infection. This study aimed to develop an in vivo system for the further dissection of cellular and humoral immune responses to SEA. C57BL/6 mice immunized subcutaneously with SEA in complete Freund adjuvant developed IH, an Arthus reaction, and DH to this antigen 5 to 9 days later. IH and the Arthus reaction, but not DH, were markedly inhibited if, 1 day before injection of SEA in complete Freund adjuvant, the mice were injected intravenously with purified T cells from the spleens of mice infected for at least 9 weeks. This in vivo model system can be used to study various aspects of cellular and humoral immune responses to SEA and their modulation. These results raise questions about the role of antibodies in the pathogenesis of granulomatous inflammation and about the mechanisms of its cellular regulation in infections with S. japonicum. PMID- 3095245 TI - Effect of gamma interferon on hydrogen peroxide production by cultured mouse peritoneal macrophages. AB - Macrophage activation is thought to be mediated via a number of T-lymphocyte products, including gamma interferon (IFN-gamma). However, our studies indicate that IFN-gamma acts as a regulator molecule rather than solely as an activator. This depends upon the status of the macrophage. IFN-gamma treatment of resting macrophages and those activated or elicited by sodium caseinate, lipopolysaccharide, or Mycobacterium bovis BCG did not result in activation, as measured by hydrogen peroxide production; however, when thioglycolate was used as an eliciting agent, incubation with IFN-gamma resulted in a dramatic increase in hydrogen peroxide production compared with that by untreated controls. PMID- 3095246 TI - Combined regional and general anesthesia for craniotomy and cortical exploration. Part II. Anesthetic considerations. PMID- 3095247 TI - Studies on Hanganutziu-Deicher antigens-antibodies. I. Hanganutziu-Deicher antibodies of IgG class in liver diseases. AB - Sera of patients with various liver diseases were examined for the presence of Hanganutziu-Deicher (H-D) antibodies by enzyme immunoassay with high-molecular weight glycoprotein (HMWGP) isolated from bovine red blood cell stromata. IgG class H-D antibodies were demonstrated in sera of 5.9% of acute hepatitis, 28.1% of chronic hepatitis and 21.9% of liver cirrhosis patients. H-D specificity of the antibodies under investigation was determined by absorption experiments. Evidence was also presented that the H-D antibodies in the liver disease sera are directed to N-glycolyl neuraminic acid (NGNA) and/or NGNA-dependent determinants of HMWGP. PMID- 3095248 TI - Monocytes constitute the only peripheral blood cell population showing an increased burst activity in multiple sclerosis patients. AB - We examined peripheral mononuclear cells (PMNC), peripheral polymorphonuclear cells (PPNC), adherent mononuclear cells, non-adherent mononuclear cells, non phagocytic mononuclear cells and non-phagocytic Percoll-fractionated mononuclear cells of multiple sclerosis (MS) patients for their spontaneous burst activity (BA). According to previous results PMNC of MS patients showed a markedly increased BA (p = 0.0002); PPNC, however, did not show significantly elevated values (p = 0.36). Further separation of PMNC and identification of the cells obtained by FITC-conjugated antibodies, esterase and Giemsa staining revealed high mean coefficients of correlation (r) between the BA and the number of esterase-positive cells (MO; r = +0.97) and the number of surface Ig-positive cells (B cells; r = +0.97). r was negative for the correlation between the BA and OKT3-positive cells (T cells; r = -0.99) and for the correlation between the BA and the number of large granular lymphocytes (r = -0.39). As in the range below 2,000 counts/10 s r is -0.5 between the BA and the number of B lymphocytes, while r is +1.0 between the BA and MO, and there are BA values below 500 counts/10 s although around 10% B cells but no MO are present, the results suggest that MO are the only cell population responsible for the increased BA in MS patients. Based on recent findings in our laboratory the results additionally indicate that in the peripheral blood interferon-gamma stimulates the BA of MO only. PMID- 3095249 TI - Relationship between cellular levels of beta-carotene and sensitivity to genotoxic agents. AB - The usefulness of an in vitro test system to predict the inhibitory effect of beta-carotene on the genotoxic activity of carcinogens/mutagens was explored. To facilitate the comparison of data obtained from cultured cells (CHO) and from exfoliated human cells, endpoints were used which can be quantitated in both cell systems: the frequency of micronuclei for estimating the effect of genotoxic agents, and cellular levels of beta-carotene as a protective agent. In CHO cells, beta-carotene inhibited the clastogenic and micronucleus-forming effect of methyl methanesulfonate (MMS) and 4-nitroquinoline-1-oxide (4NQO), but had no protective action against gallic acid, tannic acid, and aqueous extract of areca nut or H2O2. The extent of inhibition depended on the ratio of beta-carotene to MMS. Doses of beta-carotene which exerted a protective effect in vitro ranged from approximately 2 to 5 ng per 10(6) CHO cells. Comparable levels of beta-carotene were previously found to reduce the frequency of micronucleated exfoliated cells from the buccal mucosa of tobacco and areca-nut chewers (Stich et al., 1984b). PMID- 3095250 TI - Cysteine proteinases produced by cultured rabbit V2 carcinoma cells and rabbit skin fibroblasts. AB - Rabbit V2 carcinoma cells and normal rabbit skin fibroblasts produced cysteine proteinases with properties similar to those of purified rabbit liver cathepsin B. Both cell types secreted into the culture medium enzymes with an apparent Mr of 43,000, which reacted with synthetic substrates commonly used for cathepsin B. After limited proteolysis with pepsin or treatment at pH 3, the Mr = 43,000 species could be converted into forms with Mr = 34,000 and an increased specific activity. In the intracellular pool of both V2 carcinoma cells and fibroblasts, a cysteine proteinase with the same Mr of cathepsin B (27,000) was found. Despite the similarity in molecular size, substrate specificity and sensitivity to inhibitors, the tumor and fibroblast enzymes were not identical in their stability at pH greater than or equal to 7 and were produced by the 2 cell types in considerably different amounts. In terms of enzyme units and normalized to an equal cell number, the ratios of fibroblast enzyme/tumor enzyme were as follows: secreted 130-150; intracellular, 150-180. The pH stability of the cysteine proteinases was determined quantitatively by measuring the half-life of enzyme activity. At pH 8.0 and 25 degrees C the secreted tumor cysteine proteinase had a half-life of at least 5 hr, whereas the secreted fibroblast enzyme and liver cathepsin B had half-lives of 8.8 min and 4.4 min, respectively. PMID- 3095251 TI - In vivo anti-tumour activity of recombinant human and murine TNF, alone and in combination with murine IFN-gamma, on a syngeneic murine melanoma. AB - TNF, a protein released by induced macrophages, is believed to mediate, at least in part, the tumoritoxic effects of activated macrophages. In vitro, it has cytotoxic effects on transformed cells but not on normal cells, and in vivo it causes necrosis of tumours. Recently, both human and murine TNF became available as pure recombinant proteins. Subsequent work confirmed its in vitro cytotoxic activity, selective for transformed cells, and revealed other, non-cytotoxic effects on some normal cells. In vitro, the B16BL6 melanoma cells, syngeneic with C57BL6 mice, are resistant to the cytotoxic effects of rTNF but become sensitive when they are also treated with rIFN-gamma. We report that established, s.c. B16BL6 tumours in vivo can be induced to necrotize and regress by a combined systemic treatment with rTNF and murine rIFN-gamma. Although TNF is not species specific in vitro, the effects of treatment with human and murine rTNF in vivo are different: with murine rTNF, the synergism with rIFN-gamma is relatively less clear, the addition of IFN-gamma is not necessary to induce regression, toxicity is more pronounced and additional mechanisms of tumoritoxicity could be involved. Relapses are frequent but complete cures have been observed. These results give further evidence in favour of a potential clinical use of TNF in combination therapy, e.g. with IFN-gamma. However, there is still a need to develop better regimens, especially for consolidation, and to continue research in order to understand and limit the toxicity, which could be mediated by the activating effects of TNF on some normal cell types. PMID- 3095252 TI - Immunologic aspects of leprosy. AB - Twenty seven cases of leprosy from Egypt were examined. Monocytes were found to be high in peripheral blood in lepromatous cases. The percentage of small lymphocytes in blood was increased in tuberculoid patients. The immunoglobulins were higher in all types of leprosy patients than in normal persons. PMID- 3095253 TI - A pilot study on levels of organochlorine compounds in human milk in Nigeria. AB - Concentrations of some persistent organochlorine compounds (OCC) in human milk samples from Nigeria are determined. Apart from the commonly detected insecticide residues in Nigerian environment (DDT-complex, HCH-isomers and HCB), polychlorinated biphenyls (PCBs) were also found in four out of the thirty-five samples analysed; the values varied from 0.32-0.62 mg/kg milk fat. In general, concentrations of the insecticides were low. p,p'-DDD was not detected in appreciable and quantifiable levels. PMID- 3095254 TI - An international and interregional comparison of haemostatic variables in the study of ischaemic heart disease. Report of a working group. AB - Levels of haemostatic variables that may be involved in thrombogenesis have been compared in groups of men of similar mean age in communities at very low (Gambia), high (England and Czechoslovakia) or very high (Scotland and Finland) risk of ischaemic heart disease (IHD). There was a consistent gradient of higher factor VII levels with higher IHD risk and also suggestive gradients in the case of two other vitamin K dependent factors, factors II and X. Mean platelet counts were lower and mean fibrinolytic activity was greater in Gambian men than in European men. There was a suggestive though not entirely consistent association between mean fibrinogen levels and IHD risk in the groups from IHD-endemic countries. The results as a whole, and particularly those on factor VII, strengthen the case for the increasingly detailed epidemiological as well as laboratory investigation of the role of the haemostatic system in thrombogenesis and IHD. PMID- 3095256 TI - Upper airway obstruction in Hunter syndrome. AB - Patients with Hunter syndrome may have symptoms of hoarseness, stridor and breathing difficulties as a result of laryngeal and tracheal involvement. In planning their evaluation, we must prefer non-invasive methods as X-ray or CT scan, and avoid doing endotracheal intubation or bronchoscopies. Review of adult cases in the literature and description of the only case of a child with Hunter syndrome having life-threatening complications of his upper airways is discussed in this report. In this case and in the literature we cannot exclude intubation or bronchoscopy as a serious aggravating factor, causing further narrowing of the larynx. PMID- 3095255 TI - Effect of soya saponins on gold thioglucose (GTG)-induced obesity in mice. AB - The effect of oral administration of total soya saponins (TS) on the development of obesity induced by (GTG) injection was examined. In the GTG-obese group, the serum immunoreactive insulin (IRI) levels were significantly increased and food consumption was suggestively increased. In addition, sucrase activity in the intestinal mucosa was increased and the surface area of intestinal villi was significantly greater, suggesting enhanced gastrointestinal function. Oral administration of TS prevented development of obesity and prevented an increased level of IRI in GTG-obese animals. It also restored the sucrase activity and the surface area of intestinal villi to normal. Thus, TS may be effective in preventing development of obesity. PMID- 3095258 TI - ROC methodology in radiologic imaging. AB - If the performance of a diagnostic imaging system is to be evaluated objectively and meaningfully, one must compare radiologists' image-based diagnoses with actual states of disease and health in a way that distinguishes between the inherent diagnostic capacity of the radiologists' interpretations of the images, and any tendencies to "under-read" or "over-read". ROC methodology provides the only known basis for distinguishing between these two aspects of diagnostic performance. After identifying the fundamental issues that motivate ROC analysis, this article develops ROC concepts in an intuitive way. The requirements of a valid ROC study and practical techniques for ROC data collection and data analysis are sketched briefly. A survey of the radiologic literature indicates the broad variety of evaluation studies in which ROC analysis has been employed. PMID- 3095257 TI - High and low sodium acetate haemodialysis and ultrafiltration. I. Comparison of haemodynamic effects. AB - This study was undertaken to evaluate the effect of increasing the dialysate sodium concentration on haemodynamic effects, arterial blood gases and chemistries during haemodialysis and ultrafiltration. Significant changes in mean blood pressure (MBP) and heart rate (HR) were not noted; but significant differences in sodium, potassium, total protein concentration, haematocrit and plasma osmolality during dialysis and ultrafiltration were found with both dialysates. Significant differences were also noted in pCO2 during dialysis and ultrafiltration with both dialysates and increase of pH during dialysis with low sodium dialysate. Significant changes in kind and frequency of unpleasant symptoms were found with both dialysates. PMID- 3095259 TI - Legal and ethical choices in a technologic discipline: imaging centers, DRGs, and the radiologist. PMID- 3095260 TI - Home parenteral nutrition in childhood. PMID- 3095261 TI - Providing nutrition and hydration for terminally ill patients. PMID- 3095263 TI - Failure to feed: an ethical and legal discussion. PMID- 3095262 TI - The confused, the voiceless, the perverse: shall we give them food and drink. PMID- 3095265 TI - Effect of vagotomy on TRH inhibition of acid gastric secretion. AB - The effect of slow (600 micrograms) and rapid (200 micrograms) infusion of TRH on acid gastric secretion was studied in a group of healthy volunteers and a group of patients treated by truncal vagotomy. It was shown that the slow (600 micrograms) TRH infusion does not act on gastric secretion in both groups, while the rapid (200 micrograms) TRH infusion appears to significantly decrease the parameters under study during the first 15 minutes of gastric juice collection. PMID- 3095264 TI - Facing hard cases: the ethics of assisted feeding. PMID- 3095266 TI - Hospital swing-bed care in the United States. AB - As a result of federal legislation implemented in 1982, hospital beds that are used to provide both long-term care and acute care are now proliferating rapidly throughout the country. Termed swing beds, such beds are currently restricted to rural areas. However, due largely to the impacts of Medicare DRG reimbursement, pressure is mounting to expand the swing-bed approach to urban settings. Swing beds appear to fill a significant gap between the relatively intense medical needs of post-acute care patients (now discharged earlier) and the capacity of our current nursing home delivery system to meet such needs. The evolution of swing beds is marked by an unusual blend of experimentation, scientific investigation, and public policy response to community and personal health care needs. This article summarizes that evolution, highlighting research findings and key policy developments. It concludes with the current status of the national swing-bed program and issues pertinent to future directions. PMID- 3095267 TI - Evaluation of the impact of Medicare and Medicaid prospective payment on utilization of Philadelphia area hospitals. AB - The article evaluates the impact of Medicare and Medicaid DRG prospective payment on utilization in Philadelphia area hospitals. These hospitals began a combined Medicare-Medicaid DRG prospective payment at the same time after a common cost based reimbursement history. Particular attention is paid to the hospital-driven as opposed to physician-driven explanations of declining inpatient utilization. The evaluation of the Tax Equity and Fiscal Responsibility Act (TEFRA) and Diagnosis-Related Group (DRG) interventions uses an ARIMA model that removes both seasonal and autoregressive effects. Both TEFRA and the DRG payment system produced significant reductions in average length of stay, total hospital days, and hospital occupancy rates. Neither, however, had a significant effect on admissions. Hospitals with a higher proportion of Medicare and Medicaid discharges reduced their average length of stay more than other facilities. Hospitals with a higher proportion of outpatient visits to inpatient admissions also reduced inpatient length of stay more. Hospitals with higher than expected overall admissions after the introduction of the DRG program tended to have lower than expected average lengths of stay. The results lend support to the "hospital driven" interpretation of declines in average length of stay. They fail to support the contention that the DRG system will produce automatic counteracting increases in admissions in the system as a whole. PMID- 3095268 TI - Comparison of two prospective rate-setting models: the DRG and PIR models. AB - The article compares two statistical prospective hospital reimbursement models: the diagnosis-related group (DRG) model and the prospective individualized reimbursement (PIR) model. Both models are applied to the same variables from the same data set, a random sample of 10,000 hospital discharges in Maryland in 1983. For comparative purposes, the two statistical models are allowed to differ only in their treatment of the predictive variable, "patient age." The criteria of comparison and results (DRG and PIR, respectively) are: number of patient groups required (469 and 337); accuracy of prediction of length of stay (38 percent and 45 percent of the total variation is explained by the models); correction for sampling bias (0 and 2.4 percent additional explained variation); and accuracy of prediction of total charges ($526 and $262 average error per patient). PMID- 3095270 TI - Influence of complex charge and size on the uptake of 99mTc-diphosphonates in osteogenic tissue. AB - The biodistributions of six chromatographically pure 99mTc-HEDP complexes have been determined in soft tissues, normal bone and osteogenic lesions (induced with a Walker 256 tumor) in Fisher 344 rats. The physical properties of each 99mTc HEDP complex including anionic charge, partial molar volume, molecular weight and spectral characteristics are known; thus allowing structure-activity relationships to be drawn. The results indicate that the smallest, low charged, mononuclear 99mTc-HEDP complexes have the greatest uptake in bone lesions, and the highest lesion to muscle and lesion to normal bone ratios. PMID- 3095269 TI - Streptokinase and tissue plasminogen activator in acute myocardial infarction. AB - The use of thrombolytic agents for the treatment of myocardial infarction is increasing. Many community hospitals are infusing SK intravenously and those with cardiac catheterization laboratories often use intracoronary SK and angioplasty. Tissue plasminogen activator is undergoing extensive clinical trials, and reports of this research should add to our knowledge of this new therapy. Recently, benefits from thrombolytic therapy such as increased ejection fraction, improved regional wall motion, and short-term decreases in mortality have been documented. Both the GISSI trial that recruited 11,712 patients in Italy and the Netherlands trial documented significant short-term decreases in mortality after therapy with SK compared with control groups. As this information reaches the medical community, we may see an increase in the use of thrombolytic therapy during acute myocardial infarction. Additionally, community education service organizations should reemphasize the importance of seeking help early after the signs and symptoms of acute myocardial infarction appear to promote early treatment and potential salvage of greater amounts of myocardium. The long-term prognosis of patients who have been successfully reperfused and the best management after thrombolytic therapy is not yet known. Future problems and benefits from this therapy are still to be determined. PMID- 3095271 TI - Phenolic aminocarboxylate chelates of 99mTc as hepatobiliary agents. AB - A series of alkyl- and halogen-substituted derivatives of ethylenediamine di[o hydroxyphenylacetic acid] (EDDHA) and N,N'-bis[2-hydroxybenzyl] ethylenediamine N,N'-diacetic acid (HBED) were complexed with 99mTc and their biodistribution was determined in rats. All complexes displayed substantial hepatobiliary excretion; of each series, 99mTc-Br-EDDHA and 99mTc-di-Cl-HBED had the maximum amount in the gastrointestinal tract. Scintigraphic studies of 99mTc-Cl-EDDHA in dogs revealed prompt imaging of the liver followed by imaging of the gall bladder as the complex was excreted into the bile. PMID- 3095272 TI - A comparison of radiolabelled agents for thrombus imaging using a rabbit model. AB - The quantitative uptakes of five potential thrombus-localizing radiopharmaceuticals in experimental thrombi of the rabbit jugular vein have been compared to assist with the selection of a thrombus imaging agent for clinical use. Three hours after injection, 111In-platelets were clearly the agent of choice but at 18 h 99mTc-fibrinogen had more favourable characteristics. Both agents were superior to 99mTc-plasmin or its acyl derivatives, including 99mTc streptokinase-activated anisoylplasminogen. The ease of preparation coupled with favourable biological properties suggest that 99mTc-fibrinogen should be of value in the clinical situation. PMID- 3095273 TI - Effects of Lactobacillus casei on hematology and blood chemistry in normal and burned mice. PMID- 3095274 TI - Microbiological control in enteral feeding. Summary of a guidance document prepared on behalf of the Committee of the Parenteral and Enteral Nutrition Group of the British Dietetic Association. PMID- 3095275 TI - Mesenchymal chondrosarcoma: report of a case. PMID- 3095277 TI - A practical approach to uniform total body photon irradiation. AB - Photon total body irradiation (TBI) has been applied to treat several systemic malignancies. However, TBI studies have been limited by nonuniform dosimetry. A 16 MV technique was initiated to improve uniformity of dose in a practical manner. For high dose TBI, missing tissue compensators are designed from lateral tissue separations, intra-lung separations, average CT numbers of lung regions, tissue phantom ratios, and off axis ratios. A few days before treatment, CT scans are obtained and TBI is simulated in the treatment room. In the treatment room, back projections of the patient's lateral silhouette, arm outline, and CT levels are traced on a compensatory tray. Lead sheets are scribed through a schematic of the tray, cut, and fixed to their appropriate positions on the tray. Doses are verified with thermoluminescent dosemeters and ion chambers. Most measurements at the temple, chest wall, mid-thighs, and mid-knees have been within 10% of prescribed doses. About 4 hours are required for compensator fabrication and dose verification. This approach has been found practical, substantially improving dose uniformity relative to prior 60Co techniques applied at this institution. PMID- 3095276 TI - Megavoltage radiotherapy using water bolus in the treatment of Kaposi's sarcoma. AB - Between 1976 and 1983, 28 patients with Kaposi's sarcoma were treated in the Department of Radiation and Clinical Oncology of the Hadassah University Hospital in Jerusalem. Most of the patients (16, i.e. 57%) were Jews of European origin. Eighteen (64.2%) of the patients presented with severe leg edema in addition to multifocal, disseminated skin lesions. Only one patient was free of clinical disease in the lower extremities. Large, ulcerated masses were seen in three patients. The affected limbs were immersed in a water bath and irradiated with two-opposing portals to a total dose of 3000 rads. Total disappearance of the skin lesions was achieved in 89% of the patients, although the limb edema regressed completely in only 56% of the patients. PMID- 3095278 TI - A report of a randomized trial of d(15)+Be neutrons compared with megavoltage X ray therapy of bladder cancer. PMID- 3095279 TI - Detection of amplified DNA sequences in gastric cancers by a DNA renaturation method in gel. AB - A DNA renaturation method in gel was used to detect amplified DNA fragments in eight gastric cancer cell lines, KATO-III, OKAJIMA, SCH, MKN1, MKN7, MKN28, MKN45 and MKN74 cells, and tissues of three metastases of gastric cancers to lymph nodes. There were amplified DNA sequences in three gastric cancer cell lines. Judging from the intensities of the bands, HindIII-digested DNA fragments were amplified several hundred times in the KATO-III and MKN7 cell lines. DNA from OKAJIMA cell line contained multiple bands with less intensity. KATO-III cells were found to contain a homogeneously staining region in chromosome 11. PMID- 3095280 TI - Disappearance of upward proliferation and persistence of downward basal cell proliferation in rat forestomach papillomas induced by butylated hydroxyanisole. AB - The reversibility of forestomach lesions induced in rats by butylated hydroxyanisole (BHA) was examined. F344 rats were given BHA for 24 weeks, followed by the basal diet, and their forestomach lesions at weeks 24 and 96 were compared histopathologically. Hyperplasias and papillomas showing upward proliferation were found in week 24 but not in week 96. However, downward proliferation of basal cells persisted after the discontinuation of BHA administration. This finding suggests that downward growth of basal cells is not reversible and is important in the development of BHA-induced forestomach tumors in rats. PMID- 3095282 TI - Recombinant human granulocyte colony-stimulating factor induces granulocytosis in vivo. AB - Recombinant human granulocyte colony-stimulating factor (G-CSF) was prepared and its granulopoietic effects on mice were examined. When mice were injected intraperitoneally with the G-CSF daily for 14 days, marked granulocytosis occurred in the mice. The number of progenitor cells (CFU-C) was remarkably increased in the spleen. The results suggest that G-CSF plays a central role in granulocyte production in vivo. PMID- 3095281 TI - Establishment and characterization of a monocytic cell line which expresses the interleukin-2 receptor. AB - A cell line, SCC-3, was established from the pleural fluid of a patient with non Hodgkin's lymphoma. Interleukin-2 receptor (IL2-R) was found to be expressed on the cell surface by marker analysis, and morphological, cytochemical, and other marker analyses suggested a monocytic lineage. SCC-3 may be useful for studies on the role of IL2-R in monocytic cells. PMID- 3095283 TI - Carcinogenicity of chrysazin in large intestine and liver of mice. AB - The carcinogenicity of chrysazin (1,8-dihydroxy-9,10-anthracenedione) was examined by dietary administration to C3H/HeN mice. All of the effective mice (17) which were given 0.2% chrysazin diet and which survived more than 500 days developed adenomatous hyperplasia with cystic glands of the cecum. Similar lesions were also seen in the colon of mice in this group. These intestinal lesions were not obtained in any effective mouse (19) of the control group. The incidence of hepatocellular carcinoma of mice given chrysazin (4/17) was significantly higher than that of the controls (0/19). These results indicate that chrysazin is carcinogenic in mice as well as in rats. Some mechanistic aspects of the causation of these intestinal lesions and liver neoplasms are also discussed. PMID- 3095284 TI - Effects of major histocompatibility complex (RT1) and timing of fetectomy upon experimental induction of yolk sac tumor, choriocarcinoma, and teratomas in the rat. AB - Suitable conditions for inducing experimental yolk sac tumor (YST), choriocarcinoma and teratomas by simple fetectomy were studied in the rat. Tumors were inducible only when fetectomy was performed between the 7th and 14th gestational day. No YST was induced by fetectomy performed after the 15th gestational day. RT1 (major histocompatibility complex of rat) compatibility was also required for the YST induction and no tumor was induced in RT1-incompatible combinations. Only 39% of fetectomized rats produced YST after mating between an inbred strain and their backcrossed F1 hybrid. Mean survival time of the tumor bearing rats fetectomized on the 10th gestational day was 116 days. The mean diameter of the tumor was maximum in the group fetectomized in the 9th gestational day, and minimum in the group fetectomized on the 14th gestational day. PMID- 3095285 TI - Spontaneous neoplastic and non-neoplastic lesions in aging Donryu rats. AB - Spontaneous neoplastic and non-neoplastic lesions in 95 male and 96 female Donryu rats which were observed up to 120 weeks of age, were examined. The incidence of spontaneous tumors was 73.7% in males and 88.5% in females. In males, the most frequent tumors were pituitary adenomas, followed by pheochromocytomas and insulinomas. In females, uterine adenocarcinomas, mammary fibroadenomas and pituitary adenomas were the most common. Other tumors with relatively high incidences in both sexes included cortical adenomas of the adrenal gland, histiocytic sarcomas of the hematopoietic organs and granular cell tumors of the brain. Various tumors were also found in many other organs and/or tissues, although their incidences were low. The organ distribution and incidences of spontaneous tumors observed in Donryu rats were different from those in other strains of rats such as the ACI, Wistar, F344 or Sprague-Dawley strains. The main non-neoplastic lesions were observed in the lung, cervical lymph nodes and kidney of both sexes. In addition, lesions were also observed in the urinary bladder, prostate and peripheral nerves (spinal nerve roots and peripheral nerves) and/or femoralis muscle of males. Histologically, the most characteristic lesion was radiculoneuropathy with degeneration of the peripheral nerves. PMID- 3095286 TI - Epidemiologic aspects of epidermodysplasia verruciformis (L-L 1922) in Japan. AB - A survey of epidermodysplasia verruciformis (EV), a skin disease caused by human papillomavirus (HPV), was made by means of a questionnaire sent to 92 university hospitals. Replies were obtained from 68 hospitals (74% recovery) reporting 66 patients. Fewer patients were reported from north-eastern Japan than from south western Japan. Many EV patients were from families of consanguineous marriages (44%), showing a high incidence of intra-familial onset after consanguineous marriages. The complication of malignant tumors was observed in 36 of 62 cases (58%). Malignant tumors of the skin developed at an early age in EV patients. These cancers developed predominantly in exposed areas of the skin (72%). The time from onset of skin lesions to the onset of cancer seemed to be related to the nature of the lesions in EV patients. These findings suggest that the interaction of HPVs, ultraviolet rays and host factors is associated with the development of skin carcinomas. PMID- 3095287 TI - Variation in the hypoxic fraction among mouse tumors of different types, sizes, and sites. AB - Radiobiologically hypoxic fractions of 4 experimental tumors (RIF1, B16, EMT6/KU, SCCVII) of various sizes implanted subcutaneously (sc) or intradermally (id) were compared under identical conditions by using the paired survival curve assay method. The two survival curves for tumors in air-breathing and asphyxiated mice were almost parallel for EMT6/KU and SCCVII tumors, but not for RIF1 and B16 tumors. Therefore, hypoxic fractions were estimated by fitting the best parallel lines to the two sets of survival data. The values for 10 mm-diameter sc tumors in the hind legs of syngeneic mice were 4.7% for RIF1, 4.5% for B16, 14% for EMT6/KU, and 8.5% for SCCVII. The variation of the values is quite small in spite of the variety of biological characteristics of these tumors. Histological examination revealed that EMT6/KU and B16 tumors contained large necrotic areas, while SCCVII and RIF1 had small areas of necrosis. Thus, the hypoxic fraction and the proportion of necrosis in the histological specimens were not clearly correlated. The values for 6 mm and 16 mm sc EMT6/KU tumors were 5.9 and 22%, respectively, while that for 6 mm id tumors was 16%. The values for 5 mm and 18 mm sc SCCVII tumors were 0.86 and 8.4%, respectively. These results indicated that: (1) id EMT6/KU tumors had a higher hypoxic fraction than sc ones of the same size; (2) the hypoxic fraction increased with increase in tumor size in EMT6/KU tumors, while it reached a plateau at a certain size in SCVII tumors. PMID- 3095288 TI - Radioimmunoimaging of human bladder tumor xenografts in nude mice by using monoclonal antibodies. AB - Monoclonal antibodies HBJ127 and HBJ8, raised against T24 human bladder cancer cells, predominantly react with the cells in proliferating stages and with a portion of epithelial tumor cells, respectively. To investigate the in vivo localization of these monoclonal antibodies, the antibodies were labeled with radioiodine and indium-111 (111In) and injected into nude mice transplanted with human bladder tumors. The BT-11 bladder tumor had the highest concentration of radioiodinated HBJ127 and HBJ8 monoclonal antibodies, with 11.6 and 14.3% of the injected dose per gram and with a tumor-to-blood ratio of 2.6 and 1.6, respectively, at 4 days after the administration. An irrelevant monoclonal antibody did not show any specific accumulation in the BT-11 tumor. The 111In labeled HBJ127 antibody was also localized in the tumor with a higher tumor-to blood ratio than the radioiodinated antibody. The xenografted BT-11 tumor was successfully visualized with the radiolabeled HBJ127 and HBJ8 antibodies by scintigraphy. These monoclonal antibodies and the human bladder tumor xenografts may provide a good model for radioimmunoimaging and possibly therapy. PMID- 3095290 TI - Shichiro Ishikawa, M.D. (1910-1986). PMID- 3095289 TI - Different kinetics of antiviral and anticellular activities between human recombinant and natural interferon-gamma arising from different receptor-binding properties. AB - Human recombinant interferon-gamma (ReIFN-gamma) and human natural interferon gamma (IFN-gamma) showed significant differences in antiviral and anticellular activities. Namely, ReIFN-gamma exhibited antiviral activity against Sindbis virus and anticellular activity against HeLa S3 cells at significantly lower concentrations as compared with IFN-gamma at short exposure times of between 1 and 4 hr. This difference of activities was explicable in terms of different binding activities of the two IFNs to the receptors. The binding of 125I-ReIFN gamma to the receptors was competitively decreased in a dose dependent manner by unlabeled ReIFN-gamma, whereas the competition by unlabeled IFN-gamma was significantly weaker. The results of pretreatment of the cells with unlabeled ReIFN-gamma or IFN-gamma suggested that the binding of IFN-gamma to the receptors was slower than that of ReIFN-gamma. ReIFN-gamma and IFN-gamma exhibited greater colony formation-inhibitory activity against HeLa S3 cells, as compared with IFN alpha or ReIFN-beta. ReIFN-gamma also inhibited DNA, RNA and protein syntheses of HeLa S3 cells more potently than ReIFN-beta. However, the 2'-5' oligoadenylate (2'-5' A) synthetase activity in ReIFN-gamma-treated cells was significantly lower than that in ReIFN-beta-treated cells, suggesting that 2'-5' A synthetase does not play a major role in the anticellular activity of ReIFN-gamma, at least against HeLa S3 cells. PMID- 3095291 TI - Altered testosterone feedback in pubertal male rats raised on reduced caloric intake. AB - A study was conducted to explore the hypothesis that reduced caloric intake increases the negative feedback efficacy of testosterone on gonadotropin secretion. Daily subcutaneous injections of testosterone propionate in oil were administered to either age-matched (37-day-old) or weight-matched (mean = 178 g) ad libitum-fed (control) or underfed rats that received 60% of normal daily food intake from the age of 20 days. Daily doses of testosterone propionate ranged from 25 to 400 micrograms/100 g body weight. Results indicate that reduced caloric intake increases the suppression of serum LH by testosterone propionate in both age-matched and weight-matched underfed rats. On the other hand, the response of serum FSH concentrations to testosterone propionate was affected by reduced diet only in the weight-matched animals. Results suggest that the increased negative feedback of testosterone on LH secretion is a specific diet induced effect and not merely the result of reduced growth. The altered response in FSH secretion, however, may represent age-associated changes in sensitivity to testosterone rather than diet-induced effects. PMID- 3095292 TI - Vitamin A modifies the glycopeptide composition of cultured Sertoli cells. AB - Sertoli cells obtained from prepubertal rat testes were cultured in the presence or absence of retinol. Incorporation of monosaccharides and glycopeptide composition of the cells were studied under two experimental conditions. The results indicate that retinol increases the amount of mannose and glucosamine incorporated into cellular glycoconjugates. The labeled glycopeptides obtained from control and retinol-treated cells were separated by size and lectin affinity. Gel filtration analysis showed no size differences between the glycopeptides obtained from control and vitamin A-treated cells. Affinity chromatography on Concanavalin A and Wheat Germ Agglutinin of 3H-mannose-labeled glycopeptides showed that Sertoli cells cultured in the presence of retinol contain a higher percentage of high mannose-type glycopeptides compared with control cells. The effect of retinol on Sertoli cell glycopeptide composition is partially reversed by the administration of FSH. PMID- 3095294 TI - Influence of dietary lysine concentration on the oxidation of an indicator amino acid by growing boars. AB - The influence of dietary lysine concentration on the oxidation of 14C phenylalanine by growing boars was determined. Forty-five crossbred boars (30 to 40 kg) were fed a ground corn diet fortified with crystalline L-lysine to provide .28, .50, .85, 1.00, 1.25 and 1.54% total lysine. All other essential amino acids were supplemented to provide 135% of NRC (1979) recommendations. Release of 14CO2 from L-[1-14C]-phenylalanine was measured for 1 h following a meal of the experimental diet, which contained 20 mu Ci 14C-phenylalanine. Increasing dietary lysine concentration from .28 to .85% decreased 14CO2 production. Regression analysis of the data using a two-phase linear regression crossover model indicated that phenylalanine oxidation was minimized at a dietary lysine concentration of .65%. It was concluded that a concentration of .65% lysine minimized the oxidation of amino acids and provided them as possible substrates for protein deposition. The oxidation of an indicator amino acid can, therefore, be used to determine the effect of dietary lysine concentration on the partition of amino acids between metabolic fuels and body protein. PMID- 3095295 TI - The influence of dose of phenobarbital and interval to measurement on concentration of liver enzymes in barrows and gilts. AB - The administration of xenobiotics such as phenobarbital (PB) and chlorinated hydrocarbons to rats, mice and several other species has been shown to increase the level of hepatic mixed function oxidases. Experiments were conducted to establish the effect of dose of PB, sex of animals, and effect of interval from dose to measurement on concentration of hepatic enzymes in barrows and gilts 6 to 9 mo of age and weighing 100 to 120 kg. Animals given 1 or 2 g PB for 3 d had higher concentrations of microsomal protein cytochrome b5 and P-450 and NADPH cytochrome c reductase than control animals (P less than .01). Animals given 2 g PB had 3.5 times as much cytochrome P 450 as did controls. Barrows and gilts did not differ from each other in any variables measured (P less than .20). In a study of the time course of induction all animals given PB had higher levels of microsomal protein, cytochrome P-450 and reductase in 24 h than controls; however, cytochrome b5 was depressed on d 1 and was elevated by d 3. Concentration of cytochrome P-450 reached a maximum by d 7 (P less than .01); cytochromes b5 and c reductase reached a maximum by d 9 and 3, respectively (P less than .01). Levels of cytochrome P-450 were higher in gilts than in barrows on all days following PB treatment (P less than .04). Microsomal protein, cytochrome b5, cytochrome P-450 and reductase remained elevated for 6 d after the last treatment with PB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095296 TI - Effect of genetic selection for milk yield and increased milking frequency on plasma growth hormone and prolactin concentration in Holstein cows. AB - Fifty Holstein cattle, either second to fourth generation daughters of cows randomly bred to non-commercial sires originating in the Virginia Tech dairy herd (estimated mean PDM84 = -455 kg, control animals), or daughters of cows bred to commercially available sires (mean PDM84 = +368 kg, selection animals), were randomly assigned to be milked twice or thrice daily starting at parturition. Serial blood samples were collected via jugular cannulae at 30, 90 and 200 d post partum (DPP) during both the first and second lactations. Blood samples were collected for 3 h prior to and 4 h following thyrotropin releasing hormone (TRH) administration, and were analyzed for growth hormone (GH) and prolactin (PRL) concentrations. Dry matter intake, body weight and milk yield and fat content were used to calculate net energy balance (NEB) of animals at each DPP sampling period. Mean plasma GH concentrations were greater (P less than .01) in selection vs control animals both before and after TRH administration, and decreased (P less than .01) with advancing lactation (30 greater than 90 greater than 200 DPP). However, NEB was not influenced by genetic merit, implying that observed differences in GH concentrations were not due to that trait. Plasma PRL concentrations were not affected by genetic merit or DPP, but were greater (P less than .01) in the second vs first lactation. Neither PRL or GH concentrations were affected by frequency of milking. The results support the contention that increased plasma GH concentrations are associated with selection for increased milk yield. PMID- 3095297 TI - Influence of insulin and energy intake on ovulation rate, luteinizing hormone and progesterone in beef heifers. AB - Ovarian and gonadotropin responses to insulin and energy restriction were investigated in a 2 X 2 factorial experiment using 2-yr-old Brangus heifers. Thirty heifers were paired by weight and body condition, then assigned to treatment groups receiving 75 (LE) or 180% (HE) of NRC recommendations for dietary energy for maintenance. Diets were adjusted weekly to maintain daily .25 to .5 kg weight loss or 0 to .25 kg weight gain, respectively. On d 10 of the first estrous cycle subsequent to the initial 45 d of feeding, heifers within each dietary group were allocated to receive twice daily infusions of either 40 U insulin (I) or saline (C). Infusions began at 5 and 10 h postprandial and were given in six boluses, 20 min apart. Infusions continued daily until d 20 or estrus, whichever occurred first. On d 11, blood samples were collected at 15-min intervals for 12 h to determine luteinizing hormone (LH) and insulin concentrations. On d 16 to 20, twice daily im injections of 1 mg follicle stimulating hormone (FSH) were administered. Heifers were ovariectomized on d 11 after estrus. Number of corpora lutea (CL) in LE-I heifers was greater (P less than .05) in LE-C, HE-C or HE-I. Total CL weight (g) per heifer was greater (P less than .05) in HE-C and LE-I heifers than in LE-C. Individual CL wt was heavier in HE than in LE heifers (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095293 TI - Different testosterone and LH relationships in infertile men. AB - In both man and animals, changes in Leydig cell structure and function accompany seminiferous tubule damage. In this study of 1745 men attending an infertility clinic, 14% of men with elevated levels of FSH also had elevated LH levels. Groups with severe seminiferous tubule failure (eg, Sertoli Cell Only syndrome or high FSH levels) showed an inverse correlation between LH and testosterone levels. In contrast, groups with milder forms of seminiferous tubule disorders (mild hypospermatogenesis, or FSH levels in the low-normal range) showed a positive correlation between LH and testosterone. It is concluded that different mechanisms must be operative to explain the opposite relationships between LH and testosterone, and that their elucidation may point to the etiology of some forms of seminiferous tubule damage in man. PMID- 3095298 TI - Antagonistic interactions of macrolides and synergimycins on bacterial ribosomes. AB - The affinity of ribosomes for VS (virginiamycin S, a type B synergimycin) is known to be increased by VM (virginiamycin M, a type A synergimycin). Erythromycin, a macrolide, displaces ribosome-bound VS in the absence of VM, but is ineffective in its presence. In the present work, the ability of spiramycin and tylosin (macrolide subgroups) derivatives to displace ribosome-bound VS, in the presence and in the absence of VM, has been explored. All macrolides with in vitro activity displaced ribosome-bound VS: the displacement curves produced by tylosin and spiramycin derivatives virtually overlapped. When VM was added to these systems, displaced VS became readily attached to ribosomes in the case of erythromycin, did not bind appreciably within 20 min incubation in the presence of tylosin, and underwent a slow binding in the case of an N-substituted tylosin. The 16-membered macrolides (leucomycin, spiramycin and tylosin subgroups) can therefore be distinguished from the 14-membered macrolides (erythromycin subgroup) by the antagonistic effect displayed toward VM. PMID- 3095299 TI - In-vitro activity of BRL-36650, a novel beta-lactamase-stable penicillin, against multiply resistant gram-negative organisms. AB - The in-vitro activity of BRL-36650, a novel beta-lactamase-stable penicillin was tested in comparison with that of cefotaxime, ceftazidime, aztreonam and imipenem against 559 multiply resistant Gram-negative organisms, some of which were also resistant to third generation cephalosporins. BRL-36650 and imipenem were the most active antibiotics. Against 342 Enterobacteriaceae the MICs90 were: imipenem 2 mg/l, BRL-36650 4 mg/l, aztreonam 8 mg/l and cefotaxime 32 mg/l. Against 122 Pseudomonas aeruginosa the MICs90 were: BRL-36650 4 mg/l, imipenem 8 mg/l, aztreonam and ceftazidime 64 mg/l. PMID- 3095300 TI - Resistance of Mycoplasma pneumoniae to macrolides, lincomycin and streptogramin B. AB - Of four strains of Mycoplasma pneumoniae, highly resistant to erythromycin and related antibiotics, three were homogeneously resistant, but the fourth showed heterogeneous resistance, with only 1% of the cells manifesting this property. Stable, homogeneous resistance was generated in this strain in the presence of erythromycin, whereas the heterogeneous resistance was lost spontaneously on passage in the absence of antibiotics, or on treatment with acridine orange. The mechanism of induction of stable resistance appears to be different from that seen in Staphylococcus aureus. PMID- 3095302 TI - An ultra-rapid method for the study of antibiotic resistance plasmids. AB - A rapid method of isolating plasmid DNA has been developed from that of Birnboim & Doly (1979). This method allows large numbers of strains to be examined, and can be employed to isolate DNA from members of the Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, (including methicillin-resistant strains) and coagulase-negative staphylococci. Plasmids of widely differing sizes are amenable to isolation by this technique, which yields DNA of sufficient purity to allow restriction endonuclease and homoduplex analysis. PMID- 3095301 TI - BRL 20330, an oral prodrug of temocillin: bioavailability studies in man. AB - BRL 20330 is the o-methyl phenyl ester of temocillin which is well absorbed after oral administration and converted to temocillin in the body. BRL 20330 was administered to healthy subjects in a three-part cross-over study with single doses equivalent to 400, 600 and 800 mg of temocillin. Peak serum concentrations of temocillin were 9.8, 12.8 and 15.8 mg/l respectively and concentrations of 3.0 6.0 mg/l were measured at 12 h after dosing. High and prolonged concentrations of temocillin were measured in the urine. The mean urinary recovery was 22-25% and only 0.2% of unhydrolyzed BRL 20330 was detected in the urine. Little difference in the extent of absorption was noted when BRL 20330 was administered with food although the peak levels of temocillin were delayed and reduced slightly. Urinary concentrations of temocillin, even after 24 h, were bactericidal for a number of Gram-negative bacteria including multi-resistant strains. BRL 20330 was well tolerated and there was no evidence of gastro-intestinal adverse effects. PMID- 3095304 TI - Incidence of strains producing plasmid determined beta-lactamases among carbenicillin resistant Pseudomonas aeruginosa. AB - A total of 1056 strains of Pseudomonas aeruginosa isolated from human clinical specimens from patients was collected from eight laboratories in order to study the frequency of plasmid-determined beta-lactamase producers and the different enzymes represented. The strains from each laboratory comprised consecutive, non repeated, clinical isolates. In the 166 strains selected because they were carbenicillin resistant, the isoelectric points of the beta-lactamases were studied by means of analytical isoelectric focusing and the different types of plasmid-determined beta-lactamases identified. Seventy-five of the strains (45.18%) were plasmid-mediated beta-lactamase producers; the frequency varied among laboratories from 0% to 100%. Overall the most frequently identified beta lactamase type was PSE-1 (49.34%) followed by TEM-1 (37.34%). The remaining carbenicillin-resistant strains did not produce plasmid-determined beta lactamases. PMID- 3095303 TI - Successful treatment with ceftazidime of a Pseudomonas fluorescens chest infection in a myasthenic patient. PMID- 3095306 TI - Derepressed beta-lactamase synthesis in strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis. PMID- 3095305 TI - Bactericidal activity of netilmicin compared with gentamicin and streptomycin, alone and in combination with penicillin, against penicillin tolerant viridans streptococci and enterococci. AB - Netilmicin was compared with gentamicin and streptomycin for in-vitro activity against 30 strains of penicillin-tolerant streptococci including 16 strains of enterococci. Both netilmicin and gentamicin tested alone at 4 mg/l caused 99.9% kill of more than half of the 13 strains of viridans streptococci tested, whereas streptomycin, 4 mg/l, had no bactericidal effect against these strains. Netilmicin, gentamicin and streptomycin tested alone at 8.0 mg/l against 10 strains of Streptococcus faecalis resulted in 99.9% kill of six, one and zero strains respectively. Combinations of penicillin with 2 mg/l of either netilmicin or gentamicin resulted in bactericidal synergy against 12 of 13 strains of viridans streptococci and all 10 strains of S. faecalis after 18 to 24 h incubation. Parallel experiments showed that higher concentration of penicillin were required to obtain 99.9% kill of 10 streptococcal strains when 4 mg/l streptomycin was compared with 2 mg/l of the other aminoglycosides. Killing curves showed similar bactericidal synergy for netilmicin-penicillin and gentamicin-penicillin combinations against most streptococci tested after 24 h incubation but there was sometimes a greater bactericidal effect noted with netilmicin after only 6 h incubation of the broth or after 48 h incubation. The results of this in-vitro study suggest that netilmicin is at least as effective as gentamicin as a bactericidal synergic agent with penicillin against penicillin tolerant viridans streptococci and S. faecalis strains isolated from patients with endocarditis. Neither gentamicin or netilmicin were effective as bactericidal synergic agents with penicillin against 4 of 6 strains of S. faecium tested. PMID- 3095308 TI - Computerized semiautomated microbiological assay of folacin. AB - A semiautomated microbiological folacin assay system is described. A microcomputer controls sample dilutions, medium addition, turbidity determination, and data acquisition. Assay capacity is 600 tubes per day, approximately twice that of comparable manual assays. Using the automated equipment, more samples can be compared within one assay, eliminating many sources of between-assay variation in large studies. Additional advantages of this system are reduced human errors, flexibility of assay design, and multifunctional component equipment. Folacin results from chicken liver, spinach, and breakfast cereal samples show equivalent precision for manual and automated assays. PMID- 3095307 TI - Proteolytic enzymes and arachidonic acid metabolites produced by MRC-5 cells on various microcarrier substrates. AB - Human diploid fibroblasts were cultured on microcarriers made from DEAE-dextran, denatured collagen, DEAE-dextran linked to denatured collagen, and glass. Cells grown on these four substrates were examined for the production of proteolytic enzymes and arachidonic acid metabolites. Culture fluids from cells grown on the DEAE-dextran microcarriers contained the highest amounts of proteolytic enzyme activity. Both plasminogen-independent and plasminogen-dependent fibrinolytic activities were present and the plasminogen-dependent activity seemed to result from the presence of both urokinase and tissue plasminogen activator. Culture fluid from the cells grown on the glass microcarriers contained the least amount of protease activity, and nearly all of the plasminogen-activator activity seemed to be of the urokinase type. Protease activity in the culture fluids of cells grown on the other two substrates were intermediate. With regard to arachidonic acid metabolites, cells grown on the DEAE-dextran microcarriers produced the highest amounts of cyclooxygenase products but very low levels of lipoxygenase metabolites. Cells grown on the other three substrates produced comparable amounts of various cyclooxygenase products (lower than that produced by cells on the DEAE-dextran substrate). Cells grown on the glass microcarriers also produced detectable amounts of two lipoxygenase metabolites--leukotriene B4 and leukotriene C4. Inasmuch as both proteolytic enzymes and arachidonic acid metabolites regulate basic cell properties, the differential amounts of these metabolites observed in the culture fluids on the various substrates may contribute to the biological differences that exist on these substrates. PMID- 3095309 TI - Rapid liquid chromatographic determination of aflatoxins M1 and M2 in artificially contaminated fluid milks: collaborative study. AB - An international collaborative study involving 14 collaborators from 5 different countries was conducted to test a rapid liquid chromatographic (LC) method for detecting aflatoxins M1 and M2 in fluid milk. Each collaborator prepared artificially contaminated milk samples (0.078-1.31 ng M1/mL and 0.030-0.13 ng M2/mL) by adding solutions containing various concentrations of aflatoxins M1 and M2 to fresh milk. Recoveries ranged from 85.2 to 102.5% (av. 93.7%) for aflatoxin M1 and from 99.5 to 126.7% (av. 109.8%) for aflatoxin M2. Coefficients of variation averaged 21.4% (M1) and 35.9% (M2). An analysis of variance was calculated from combined data to determine variance components. The within laboratory variations (So) (repeatability) were 27.9% (M1) and 23.9% (M2), and the among-laboratory variations (Sx) (reproducibility) were 44.5% (M1) and 64.7% (M2). No visual differences were determined between normal or reverse phase LC for contaminated samples; however, there were an insufficient number of collaborators using normal phase to give meaningful separate statistical data. For 26 observations of uncontaminated milk, 3 false M1 positives were reported for normal phase LC determinations and 2 false M1 positives were reported for reverse phase LC determinations. Three normal phase and 11 reverse phase false M2 positives were reported for 104 observations in uncontaminated milk. The reverse phase LC method for determination of aflatoxins M1 and M2 in fluid milk has been adopted official first action. PMID- 3095312 TI - Mysterious MAOI hypertensive episodes. AB - A reliable patient experienced several MAOI-associated acute hypertensive episodes that could not be accounted for by indiscretions of diet or contraindicated medications. The sparse literature on such mysterious hypertensive crises reveals them to be uncommon but not unknown. The mechanism is as yet disturbingly unexplained. An incidental finding in this case was that the novel MAOI l-deprenyl did not result in hypertensive crises but, in contrast to conventional MAOIs, was ineffective against panic attacks. PMID- 3095310 TI - Thin layer chromatographic confirmation of aflatoxin M1 extracted from milk. AB - Aflatoxin M1 can be confirmed directly on a thin layer plate by reacting the toxin with a mixture of reagents containing p-anisaldehyde. This confirmatory procedure requires only 2 elutions in the same direction using 2 different solvents. The mixture containing p-anisaldehyde is overspotted on M1 after the plate has been developed in toluene-ethyl acetate-ethyl ether-formic acid (25 + 35 + 40 + 5). The plate is heated at 110 degrees C for 10 min and then developed in hexane-acetone-chloroform (15 + 50 + 35). The Rf value of the green fluorescent derivative is less than that of the M1 standard. This confirmatory procedure requires only one-dimensional TLC, so several sample extracts and the standard can be run simultaneously. The minimum detectable quantity of aflatoxin M1 on the TLC plate with this test is 0.3 ng. p-Anisaldehyde reagent solution may also be used as a spray reagent for the confirmation of aflatoxin M1. The procedures described were satisfactory for confirming the mycotoxin in spiked samples of powdered and liquid milk. PMID- 3095313 TI - Synthesis of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) in exocrine glands and its control by secretagogues. AB - 1-O-Alkyl-2-acetyl-sn-glycero-3-phosphocholines (platelet-activating factor (PAF] stimulate exocytosis in isolated lobules from guinea pig parotid glands or pancreas by an acetylcholine-like mechanism (Soling, H. D., Eibl, H. J., and Fest, W. (1984) Eur. J. Biochem. 144, 65-72). We show here that both tissues are able to synthetize PAF themselves. Isolated guinea pig parotid gland acini incorporate labeled acetate into the 2-position of PAF. Stimulation with A23187 or carbamoylcholine lead to a significant stimulation of this process. The newly synthetized PAF is partially released into the medium. Addition of lyso-PAF to the incubation medium does not significantly affect the rate of incorporation of labeled acetate into PAF in the absence or presence of carbamoylcholine. Isolated pancreatic lobules are also able to incorporate labeled acetate into PAF, and cholecystokinin and caerulein lead to a strong stimulation of this process. Incorporation of radioactive lyso-PAF into PAF, but not into 1-O-alkyl-2-long chain acyl-sn-glycero-3-phosphocholine was also significantly stimulated by carbamoylcholine in isolated parotid acini. Under these conditions, the time dependent stimulation of amylase release paralled that of lyso-PAF incorporation into PAF. The same holds for the concentration dependency of the carbachol effect on these two parameters. In isolated pancreatic lobules, caerulein also stimulated the incorporation of lyso-PAF into PAF. Pulse-chase experiments with radioactive lyso-PAF indicate that stimulation of incorporation of radioactive lyso-PAF into PAF represents increased net synthesis of PAF rather than increased PAF-turnover. Using the platelet aggregation test, substantial amounts (0.79 nmol/g) of PAF could be determined in isolated acini from guinea pig parotid glands. PMID- 3095311 TI - Enzyme-linked immunosorbent assay of aflatoxin B1 in naturally contaminated corn and cottonseed. AB - Naturally contaminated corn and cottonseed samples were screened for aflatoxin B1 (AFB1) by a direct competitive enzyme-linked immunosorbent assay (ELISA). Samples were blended 5 min in an extraction solvent of methanol-water-dimethylformamide (70 + 29 + 1) and filtered. Filtrates were assayed by direct competition between AFB1 in the corn and cottonseed samples and AFB1-peroxidase conjugate for binding to specific antibody adsorbed to a solid phase microtiter plate. Standard curves prepared using the extract of AFB1-free corn and cottonseed samples, and extraction solvent only, showed negligible interference by the sample extract in the performance of ELISA. The AFB1 content in corn and dehulled cottonseed samples as determined by ELISA ranged from 7 to 422 micrograms/kg and 7 to 3,258 micrograms/kg, respectively. When ELISA estimates of AFB1 in corn were compared with values obtained by thin layer chromatography (CB method), the correlation coefficient (n = 10) was 0.95. Average interassay and subsample coefficients of variation for ELISA in corn were 21.4 and 22.0%, respectively. When ELISA estimates of AFB1 in cottonseed were compared with values obtained by liquid chromatography (Pons method), the correlation coefficient (n = 15) was 0.96. Using this ELISA, 36 duplicate sample extracts can be screened for AFB1 in less than 2 h. PMID- 3095314 TI - Biosynthetic labeling of hypusine in mammalian cells. Carbon-hydrogen bond fissions revealed by dual labeling. AB - Using a dual-label technique in which 3H- and 14C-labeled forms of putrescine and of spermidine were employed as biosynthetic precursors of hypusine, two -C-H bond cleavages were detected during production of this unique amino acid in Chinese hamster ovary cells. One of these cleavages occurs at C-1 of the 4-aminobutyl group during its transfer from the secondary amine nitrogen of spermidine to the nitrogen at the epsilon-position of a specific lysine residue in the polypeptide precursor of eukaryotic initiation factor 4D. Breakage of the other -C-H bond takes place at C-2 in this aminobutyl segment after it has been coupled to lysine to form the intermediate deoxyhypusine residue. Hydroxylation at this carbon atom, which constitutes the last step in hypusine biosynthesis, is the cause of bond cleavage. The data obtained are consistent with a notion that no additional C-H bond fissions occur during hypusine biosynthesis. Our findings permit suggestion of a mechanism for enzymic aminobutyl group transfer in which 4 aminobutyraldehyde produced by oxidative cleavage of spermidine is coupled with the epsilon-amino group of a specific lysine residue to form an enzyme-bound imine intermediate. PMID- 3095315 TI - Transforming growth factor beta regulates the inhibitory actions of epidermal growth factor during granulosa cell differentiation. AB - The effects of transforming growth factor beta (TGF-beta) on epidermal growth factor (EGF) receptor content and EGF action were studied in cultured granulosa cells from immature diethylstilbestrol-implanted rats. During follicle stimulating hormone (FSH)-induced differentiation in vitro, EGF receptors increased by 20-fold as measured by the binding of 125I-EGF to the intact cells. Addition of TGF-beta during the 48-h culture period amplified the stimulatory effects of FSH on EGF receptors up to 2-fold, with ED50 and maximal concentrations of 2.5 and 8 pM, respectively. Also TGF-beta alone in amounts from 1.6 to 16 pM increased EGF receptor content 4-fold. The stimulatory effects of TGF-beta were due to increased numbers of EGF receptors/cell, since the growth factor had no effect on the Kd (3-5 X 10(-11) M) of the high-affinity EGF binding site. TGF-beta action was observed within 20 h of granulosa cell culture and was maximal by 48 h of a 96-h culture. The stimulatory actions of TGF-beta in gonadotropin-induced cells were exerted through the cAMP effector system of the granulosa cell, since the growth factor also amplified the induction of EGF receptors by cholera toxin, forskolin, and 8-bromo-cAMP. The augmentation of EGF receptors by TGF-beta resulted in a parallel 2-fold increase in the inhibitory effects of EGF on FSH-induced cAMP production and luteinizing hormone receptor expression during granulosa cell development. TGF-beta did not increase granulosa cell numbers during culture although it elevated [3H]thymidine incorporation into DNA by 2-fold over that of FSH-treated cells. These results indicate that TGF beta regulates the effects of both FSH and EGF during granulosa cell differentiation and provides evidence that ovarian function may be controlled by the combined actions of gonadotropins and multiple growth factors. PMID- 3095316 TI - Immunochemical analysis of mammalian RNA polymerase II subspecies. Stability and relative in vivo concentration. AB - Three subspecies of RNA polymerase II, designated IIO, IIA, and IIB, have been described in a variety of eukaryotic cells and shown to differ in the molecular weight of their largest subunit, designated IIo, IIa, and IIb, respectively. The objectives of this study were to establish the in vivo molecular structure of RNA polymerase II in mammalian cells and to examine conditions that influence the stability of RNA polymerase II subspecies. Subunit affinity-purified antibodies were used to determine the relative concentration of subunits IIo, IIa, and IIb in crude extracts of calf thymus tissue, cultured bovine kidney cells, and HeLa cells. HeLa cells contain exclusively RNA polymerase IIO whereas both cultured bovine kidney cells and calf thymus tissue contain RNA polymerases IIO and IIA. RNA polymerase IIB was not detected at significant levels in any of the cell extracts examined. Cell extracts were aged at either 4 degrees or 37 degrees C and the stability of RNA polymerases IIO and IIA determined by protein blotting. In the presence of buffer normally used for RNA polymerase purification, subunit IIo disappears from calf thymus extracts within 24 h at 4 degrees C or within 5 min at 37 degrees C. RNA polymerase IIO is partially stabilized by the inclusion of protease inhibitors and further stabilized by the presence of relatively high concentration of EDTA and EGTA. The prior fractionation of nuclei does not have an appreciable effect on RNA polymerase II stability. An increase in the amount of reducing agent causes a dramatic reduction in the stability of subunit IIo. The following manuscript (Bartholomew, B., Dahmus, M. E., and Meares, C. F. (1986) J. Biol. Chem. 14226-14231) examines the transcriptional activity of RNA polymerases IIO and IIA in reactions dependent on the major late promoter of adenovirus-2. Photoaffinity labeling of subunits IIo and IIa, relative to their concentration in the transcription extract, indicates that the transcriptional activity of RNA polymerase IIO is greater than 10 times that of IIA. PMID- 3095318 TI - Differential subcompartmentation of terminal glycosylation in the Golgi apparatus of intestinal absorptive and goblet cells. AB - Two terminal glycosyltransferases, a sialyltransferase and the blood group A alpha 1,3 N-acetylgalactosaminyltransferase, were found to exhibit differential subcompartmentation in the Golgi apparatus of intestinal goblet and absorptive cells. As expected from their role in terminal glycosylation, the two glycosyltransferases and their products, sialic acid residues and blood group A substance, were localized in the trans cisternae of the Golgi apparatus of goblet cells. In contrast, however, they were found throughout the Golgi apparatus stack of adjacent absorptive cells, with the exception of the fenestrated first cis cisterna. The results are in contrast to the general view that enzymes in the glycosylation pathway are arranged in a cis to trans gradient across the Golgi apparatus and that such polarized distributions may instead be cell type specific. PMID- 3095317 TI - A metalloproteinase from human rheumatoid synovial fibroblasts that digests connective tissue matrix components. Purification and characterization. AB - Human rheumatoid synovial cells in culture stimulated with the conditioned culture medium of rabbit macrophages secrete three distinct latent metalloproteinases. One of them, a proteinase that digests proteoglycan and other connective tissue matrix components, was purified as two active forms after activation with 4-aminophenylmercuric acetate. The two forms were homogeneous on sodium dodecyl sulfate-gel electrophoresis with Mr = 45,000 and Mr = 28,000, whereas the latent precursor was estimated to have Mr = 51,000 by gel permeation chromatography. Both active enzymes had optimal activity at pH 7.5-7.8 and were inhibited by EDTA and 1,10-phenanthroline but not by inhibitors for cysteine, serine, or aspartic proteinases. Removal of Ca2+ from the enzyme solution resulted in a complete loss of activity that could be fully restored by the addition of 1 mM Ca2+. The activity of the apoenzyme was restored by the addition of 0.5 mM Zn2+, 5 mM Co2+, or 5 mM Mn2+ in the presence of Ca2+ but not by each metal ion alone. The identical digestion patterns of reduced, carboxymethylated protein substrates indicated that both active forms of the enzyme have the same substrate specificity. The enzyme degraded cartilage proteoglycans, type I gelatin, type IV collagen, laminin, and fibronectin, and removed the NH2-terminal propeptides from chick type I procollagen. This enzyme may play a role in the normal turnover of the connective tissue matrix as well as in the joint destruction of chronic synovitis. PMID- 3095319 TI - A filamentous form of Drosophila casein kinase II. AB - The self-aggregation behavior of casein kinase II from Drosophila melanogaster has been analyzed by velocity sedimentation and electron microscopy. The results indicate that self-aggregation involves the formation of linear polymers or filaments approximately 10 nm in diameter. In the presence of 1 mM EDTA filament length was inversely proportional to total ionic strength over a range from 0.05 to 0.28, and filaments as long as 0.5 micron were observed at the lower ionic strengths. Similar results were obtained in the presence of 10 mM MgCl2, but two additional ionic strength-dependent phenomena were superimposed. First, at subphysiological ionic strength side-to-side aggregation of filaments occurred which resulted in enzyme precipitation. Second, at physiological ionic strength a time- and temperature-dependent increase in filament length occurred which generated polymers up to 5 micron long. No side-to-side aggregation occurred under the latter conditions. Filamentous forms of the kinase could be readily reconverted to the standard alpha 2 beta 2 tetramer by the addition of high salt. Filamentous casein kinase II was observed over a pH range from 6.8 to 8.0, at enzyme concentrations ranging from 6 to 150 micrograms/ml, in the presence of ATP, and at MgCl2 concentrations from 1 to 10 mM. However, time-dependent growth of long filaments was not observed at Mg2+ concentrations below 10 mM. The conditions under which filaments are observed in vitro suggest that they may also exist in vivo. The possibility that filament formation plays a role in the regulation of casein kinase II activity is discussed. PMID- 3095320 TI - Eukaryotic initiation factor 4D. Purification from human red blood cells and the sequence of amino acids around its single hypusine residue. AB - Eukaryotic initiation factor 4D (eIF-4D) was purified from human red blood cells by a simple 5-step procedure. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that most of the preparations of eIF-4D were composed of variable amounts of two closely migrating forms of the factor, each of which contained a single residue of the unique amino acid hypusine. The structural similarity of the two forms of human eIF-4D was evidenced by the indistinguishable patterns of radioactivity on peptide maps of tryptic digests prepared from radioiodinated samples. A peptide containing the single hypusine residue was readily isolated from a tryptic digest of human eIF-4D by virtue of its high positive charge and hydrophilic character. Amino acid sequence determination on this peptide revealed the following primary structure around hypusine: Thr-Gly-hypusine-His-Gly-His-Ala-Lys. PMID- 3095322 TI - The 5'-flanking sequences of Drosophila melanogaster tRNA5Asn genes differentially arrest RNA polymerase III. AB - Three tRNA5Asn genes have been subcloned from a tRNA gene cluster isolated from the cytogenetic locus 42A of Drosophila melanogaster. The three tRNAAsn genes, contained on plasmids pAsn6, pAsn7, and pAsn8, have identical mature tRNA coding regions but have different 5'- and 3'-flanking sequences. In vitro transcription in Drosophila Schneider S3 cell-free extracts showed the tRNAAsn genes had different transcription efficiencies. pAsn8 had a transcription efficiency of approximately 8 transcripts/gene/h, whereas pAsn6 was a less active template at 5 transcripts/gene/h. pAsn7 was the poorest template at 1.5 transcripts/gene/h. Exchanging 5'-flanking regions of the tRNAAsn genes showed that the differences in transcription efficiencies were attributable to the corresponding 5'-flanking region. Transcription of each of the tRNAAsn genes revealed a different optimum for KC1 concentration for each template which also was directly attributable to the corresponding 5'-flanking region. The "salt effect" is not related to the ability of the three tRNAAsn genes to sequester transcription factors as determined using the stable complex competition assay. Rather, this effect appears to be due to the ability of the respective 5'-flanking regions to interact with RNA polymerase III. The poorest transcription template, pAsn7, was a better competitor in the stable complex formation assay than either pAsn8 or pAsn6. We conclude that the pAsn7 stable complex binds and functionally arrests RNA polymerase III in the initiation reaction. PMID- 3095321 TI - Interactions of pyridine nucleotides with redox forms of the flavin-containing NADH peroxidase from Streptococcus faecalis. AB - The flavin-containing NADH peroxidase of Streptococcus faecalis 10C1, which catalyzes the reaction: NADH + H+ + H2O2----NAD+ + 2H2O, has been purified to homogeneity in our laboratory for analyses of both its structure and redox behavior. Our findings indicate that the enzyme is a tetramer of four apparently identical subunits (Mr = 46,000/subunit), each containing one FAD coenzyme and a second non-flavin, nonmetal redox center. There is no evidence of nonequivalence among the flavins. Dithionite reduction of the enzyme occurs in two steps, with end points of 0.96 and 2.05 eq/FAD. The first step generates a two-electron reduced form of the enzyme (EH2) which is spectrally identical with that generated by aerobic addition of NADH. Our studies suggest that the long wavelength absorbance band (lambda max approximately 540 nm) exhibited by this form results from charge-transfer interaction between the reduced non-flavin redox center and the oxidized flavin. A second type of long-wavelength charge transfer absorbance band (lambda max approximately 770 nm) is generated on anaerobic addition of 1 eq of NADH to EH2 and results from interaction between oxidized FAD and the reduced pyridine nucleotide. Either the EH2 X NAD+ or the EH2 X NAD+ X NADH forms may be involved in the catalytic mechanism of the enzyme, as both are reactive with hydrogen peroxide. PMID- 3095324 TI - Complexes of heparin proteoglycans, chondroitin sulfate E proteoglycans, and [3H]diisopropyl fluorophosphate-binding proteins are exocytosed from activated mouse bone marrow-derived mast cells. AB - The predominant [3H]diisopropyl fluorophosphate (DFP)-binding proteins that are released from the secretory granules of activated mouse bone marrow-derived mast cells (BMMC) are demonstrated to have an isoelectric point of approximately 9.1 and to be complexed to proteoglycans. Upon Sepharose CL-2B chromatography of the supernatants of calcium ionophore-activated BMMC, 67-78% of the total exocytosed [3H]DFP-binding proteins co-eluted in the excluded volume of the column as a greater than 1 X 10(7) Mr complex bound to 4-7% of the total exocytosed proteoglycans. The remainder of the exocytosed proteoglycans, which filtered in the included volume of the gel filtration column with a Kav of 0.66, contained chondroitin sulfate E glycosaminoglycans. After dissociation of the large Mr complexes of [3H]DFP-binding proteins-proteoglycans with 5 M NaCl and removal of the proteins via phenyl-Sepharose chromatography, the proteoglycans filtered from the Sepharose CL-2B column as a single peak with a Kav of 0.66. The susceptibility of 24-59% and 36-76% of the glycosaminoglycans in the large Mr complex to degradation by nitrous acid and chondroitinase ABC, respectively, indicated the presence of proteoglycans that contained heparin and chondroitin sulfate glycosaminoglycans. Disaccharide analysis revealed that the chondroitin sulfate in the high Mr complex was chondroitin sulfate E. Following chondroitinase ABC treatment of the large Mr complex, the residual heparin proteoglycans filtered on Sepharose CL-4B under dissociative conditions with the same Kav as the original, untreated proteoglycans. Thus, the protein-proteoglycan complexes that are exocytosed from activated mouse BMMC contain approximately equal amounts of proteoglycans of comparable size that bear either predominantly heparin or predominantly chondroitin sulfate E glycosaminoglycans. The demonstration of these secreted complexes indicates that the intragranular protease-resistant heparin and chondroitin sulfate E proteoglycans in the T cell factor-dependent BMMC bind serine proteases throughout the activation-secretion response. PMID- 3095323 TI - A mitochondrial DNA polymerase from embryos of Drosophila melanogaster. Purification, subunit structure, and partial characterization. AB - The mitochondrial DNA polymerase has been purified to near-homogeneity from early embryos of Drosophila melanogaster. Sodium dodecyl sulfate gel electrophoresis of the highly purified enzyme reveals two polypeptides with molecular masses of 125,000 and 35,000 daltons, in a ratio of 1:1. The enzyme has a sedimentation coefficient of 7.6 S and a Stokes radius of 51 A. Taken together, the data suggest that the D. melanogaster DNA polymerase gamma is a heterodimer. DNA polymerase activity gel analysis has allowed the assignment of the DNA polymerization function to the large subunit. The DNA polymerase exhibits a remarkable ability to utilize efficiently a variety of template-primers including gapped DNA, poly(rA).oligo(dT) and singly primed phi X174 DNA. Both the crude and the highly purified enzymes are stimulated by KCl, and inhibited by dideoxythymidine triphosphate and by N-ethylmaleimide. Thus, the catalytic properties of the near-homogeneous Drosophila enzyme are consistent with those of DNA polymerase gamma as partially purified from several vertebrates. PMID- 3095325 TI - A high molecular weight protease in the cytosol of rat liver. I. Purification, enzymological properties, and tissue distribution. AB - Rat liver cytosol has low hydrolytic activity against [3H]methylcasein at neutrality, but activity increases greatly on addition of various compounds such as poly-L-lysine, N-ethylmaleimide, and sodium dodecyl sulfate, suggesting that it contains latent proteolytic activity. The latent enzyme was found to be stabilized in the presence of 20% glycerol and to be activated by addition of poly-L-lysine. The latent enzyme was purified from a crude extract of rat liver to apparent homogeneity in the presence of 20% glycerol by conventional chromatographic techniques. The purified enzyme showed endoproteolytic activity toward various proteins when it was activated by the compounds listed above. It preferentially degraded N-substituted tripeptide substrates with a basic amino acid at the carboxyl terminus, as well as peptides containing neutral hydrophobic amino acids. It did not require activation for these peptidase activities, in contrast to its activity toward large proteins. Interestingly, a proteinase and a trypsin-like and a chymotrypsin-like peptidase activity could not be separated by customary chromatographic methods but were distinguishable by their sensitivities to various inhibitors, activators, and covalent modifiers, suggesting that the enzyme has three distinct active sites within a single protein. The enzyme seems to be a seryl endopeptidase showing maximal activity at neutral and weakly alkaline pH values. Thus, the enzyme is a unique protease with latent multifunctional catalytic sites. The distribution of the protease in soluble extracts of various rat tissues and cells was examined quantitatively by an enzyme immunoassay. The enzyme level was highest in liver and also in spleen, stomach, lung, small intestine, and kidney, but was low in heart, diaphragm, skeletal muscle, brain, and skin. The concentrations of enzyme in some established cell lines including hepatoma and rat kidney cells were comparable to that in normal liver hepatocytes. The enzyme was found mainly in the cytosol fraction, although a small amount was associated with microsomal membranes, suggesting that it is an extralysosomal protease. Immunohistochemical staining of the liver and skeletal muscles showed that the protease is distributed diffusely in panlobular hepatocytes with slight centrilobar predominance and is present in Kupffer cells, vascular endothelial cells, and bile duct epithelial cells in the liver and also diffusely in the intermyofibrillar spaces and vascular endothelial cells in skeletal muscle. The quantitative data obtained in the present study indicate the presence of the protease in the cytosol fraction of all rat tissues.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3095326 TI - Inhibition of cyclooxygenase activity and platelet aggregation by epoxyeicosatrienoic acids. Influence of stereochemistry. AB - Certain epoxyeicosatrienoic acids (EETs) that were not cyclooxygenase substrates were effective cyclooxygenase inhibitors. Both (+/-)-14,15-cis-EET and (+/-)-8,9 cis-EET inhibited purified enzyme at concentrations from 1 to 50 microM; (+/-) 11,12-cis-EET was ineffective at concentrations below 100 microM. For the case of 14,15-cis-EET, only the (14R,15S)-stereoisomer was active. Other isomers including (14S,15R)-cis-EET, (14R,15R)-trans-EET, (14S,15S)-trans-EET, and the erythro and threo vicinal 14,15-diols were inactive. In addition to their effects on isolated enzyme preparations, cyclooxygenase activity in platelet suspensions, reflected by thromboxane B2 formation, was also inhibited by (14R,15S)-cis-EET and (+/-)-8,9-cis-EET but not by the other isomers. Thus potency and stereospecificity requirements were maintained for cyclooxygenase within intact platelets. Unlike the stereospecific inhibition of the cyclooxygenase enzyme, platelet aggregation induced by arachidonic acid was inhibited by all EET isomers at concentrations from 1 to 10 microM with no evident stereospecificity. Inhibition of aggregation was not uniformly associated with inhibition of thromboxane B2 formation; ordinarily, these two parameters correlate closely. This dissociation was not maintained for another biochemical process involved in platelet activation. For instance, there was a uniform correlation between inhibition of phosphorylation of a 40-kDa platelet protein and inhibition of aggregation. Our results suggest that effects of EET may originate from either stereospecific or nonspecific mechanisms. Definition of such mechanisms may be important to appreciate any physiological relevance of these substances. PMID- 3095327 TI - Antibiotic-impregnated cement in total joint arthroplasty. PMID- 3095328 TI - Method to determine antibacterial activity of silver sulfadiazine creams. PMID- 3095329 TI - Cost containment/cost reduction: the economic impact of burn DRGs. PMID- 3095330 TI - Fluorescent lighting enhances chemically induced papilloma formation and increases susceptibility to tumor challenge in mice. AB - To study whether fluorescent lighting at work might increase carcinogenesis, hairless mice were exposed to a bank of six 36 W standard fluorescent lamps (neutral-white) every workday for 8 h at an illuminance level of 1,000 lx. For comparison, other mice were exposed to UVB radiation or to simulated solar radiation. In experiment A the animals were irradiated for 6 weeks prior to the application of 7,12-dimethyl-benzanthracene once and--following an interval of 2 days--for 10 weeks after DMBA application. The number of blue nevi and papillomas was enhanced by exposure to all spectra 10 weeks after chemical tumor induction. In experiment B the animals were irradiated for 6 weeks prior to the transplantation of UV-induced fibrosarcoma cells from syngeneic mice into the dorsal and ventral skin. Within the following 4 months fibrosarcoma developed in the dorsal skin exposed to the fluorescent lighting and to the UVB radiation, as well as in the non-irradiated ventral skin of 10-20% of the mice. The results suggest that fluorescent lighting as used in certain work environments may increase carcinogenesis caused by other factors. PMID- 3095331 TI - Enhancing effects of rodent malaria on aflatoxin B1-induced hepatic neoplasia. AB - The interaction between aflatoxin and malaria was tested for its usefulness as a model for hepatic tumor induction in rats. Male Buffalo rats which received aflatoxin B1 (AFB1) followed by Plasmodium berghei infection developed more preneoplastic lesions in the liver compared to those given AFB1 alone. No preneoplastic lesions were found in the liver of control and malarial-treated animals. These findings suggest that the malarial parasite facilitates liver tumor development initiated by AFB1 in rats. PMID- 3095332 TI - Quantitative evaluation of DNA binding data for risk estimation and for classification of direct and indirect carcinogens. AB - Investigation of covalent DNA binding in vivo provided evidence for whether a test substance can be activated to metabolites able to reach and react with DNA in an intact organism. For a comparison of DNA binding potencies of various compounds tested under different conditions, a normalization of the DNA lesion with respect to the dose is useful. A covalent binding index, CBI = (mumol chemical bound per mol DNA nucleotide)/(mmol chemical administered per kg body weight) can be determined for each compound. Whether covalent DNA binding results in tumor formation is dependent upon additional factors specific to the cell type. Thus far, all compounds which bind covalently to liver DNA in vivo have also proven to be carcinogenic in a long-term study, although the liver was not necessarily the target organ for tumor growth. With appropriate techniques, DNA binding can be determined in a dose range which may be many orders of magnitude below the dose levels required for significant tumor induction in a long-term bioassay. Rat liver DNA binding was proportional to the dose of aflatoxin B1 after oral administration of a dose between 100 micrograms/kg and 1 ng/kg. The lowest dose was in the range of general human daily exposures. Demonstration of a lack of liver DNA binding (CBI less than 0.1) in vivo for a carcinogenic, nonmutagenic compound is a strong indication for an indirect mechanism of carcinogenic action. Carcinogens of this class do not directly produce a change in gene structure or function but disturb a critical biochemical control mechanism, such as protection from oxygen radicals, control of cell division, etc. Ultimately, genetic changes are produced indirectly or accumulate from endogenous genotoxic agents. The question of why compounds which act via indirect mechanisms are more likely to exhibit a nonlinear range in the dose-response curve as opposed to the directly genotoxic agents or processes is discussed. PMID- 3095333 TI - Plasminogen activator in mammalian skeletal muscle: characteristics of effect of denervation on urokinase-like and tissue activator. AB - Analyses were made of the fibrinolytic, plasminogen-activating system in skeletal muscle to determine if a regulating influence of the nerve could be detected on these enzymes. Young male mice underwent right sciatic neurectomy. Extracts were prepared from denervated muscle at 2-17 d after axotomy and compared with controls. Using a cascade-style biochemical assay (Ranby, M., B. Norrman, and P. Wallen, 1982, Thromb. Res., 27:743-748) we found that low levels of plasminogen activator (PA) were present in adult, innervated mouse muscle, but that denervation resulted in a marked time-dependent increase in enzyme activity. Qualitative separation showed an eightfold increase in urokinase-like PA with moderate elevation of tissue PA activity after 10 d. Fibrin zymography (Granelli Piperno, A., and E. Reich, 1978, J. Exp. Med., 148:223-234) revealed clear zones of lysis corresponding to molecular masses of 48 kD for urokinase-like PA and 75 kD for tissue PA, consistent with the molecular masses found for these enzymes in other tissues of the mouse (Dano, K., P. A. Andreasen, J. Grondahl-Hansen, P. Kristensen, L. S. Nielsen, and L. Skriver, 1985, Adv. Cancer Res., 44:139-266). In other studies we have shown that PA-activated plasmin readily attacks critical adhesive basement membrane molecules. The present results indicate that enzymes involved in plasminogen activation, particularly urokinase-like PA, rapidly increase after axotomy, suggesting they may have a role early in muscle denervation. Similar alterations in PA activity might underlie the elimination of polyneuronal innervation during mammalian muscle development. Certain neuromuscular diseases may also involve activation of these enzymes, resulting in degradation of basement membrane zone components and, therefore, warrant further study. PMID- 3095334 TI - A-CAM: a 135-kD receptor of intercellular adherens junctions. II. Antibody mediated modulation of junction formation. AB - Intercellular adherens junctions between cultured lens epithelial cells are highly Ca2+-dependent and are readily dissociated upon chelation of extracellular Ca2+ ions. Addition of Ca2+ to EGTA-treated cells results in the recovery of cell cell junctions including the reorganization of adherens junction-specific cell adhesion molecule (A-CAM), vinculin, and actin (Volk, T., and B. Geiger, 1986, J. Cell Biol., 103:000-000). Incubation of cells during the recovery phase with Fab' fragments of anti-A-CAM specifically inhibited the re-formation of cell-cell adherens junctions. This inhibition was accompanied by remarkable changes in microfilament organization manifested by an apparent deterioration of stress fibers and the appearance of fragmented actin bundles throughout the cytoplasm. Incubation of EGTA-dissociated cells with intact divalent anti-A-CAM antibodies in normal medium had no apparent inhibitory effect on junction formation and did not affect the assembly of actin microfilament bundles. Moreover, adherens junctions formed in the presence of the divalent antibodies became essentially Ca2+-independent, suggesting that cell-cell adhesion between them was primarily mediated by the antibodies. These studies suggest that A-CAM participates in intercellular adhesion in adherens-type junctions and point to its involvement in microfilament bundle assembly. PMID- 3095336 TI - Studies on proteins that co-purify with smooth muscle vinculin: identification of immunologically related species in focal adhesions of nonmuscle and Z-lines of muscle cells. AB - Membrane extracts from chicken smooth muscle contain, along with filamin, vinculin and alpha actinin, a group of polypeptides that have the ability to interact with the "barbed end" of actin filaments. These low molecular mass polypeptides were designated as HA1 (Wilkins, J.A., and S. Lin, 1986, J. Cell Biol., 102:1085-1092). In this study, polyclonal antibodies raised against the HA1 preparation were used to study the cellular localization and tissue distribution of these polypeptides. Immunofluorescence experiments revealed a primary localization of staining at the ends of stress fibers on the ventral surface of cultured chicken embryo fibroblasts, i.e., those areas known as the focal adhesions. Specific staining was also seen at the Z-lines of both skeletal muscle myofibrils and cultured embryonic heart cells. Immunoblotting analyses of proteins from different tissues prepared to avoid proteolytic degradation showed a much different pattern than that of HA1 itself. Immunoreactive polypeptides with reduced molecular masses of 200,000 and 150,000 D were found in smooth muscle and fibroblasts while 200 and 60 kD polypeptides were found in cardiac muscle tissue. The antibodies recognized 60- and 31-kD polypeptides on immunoblots of chicken breast muscle. The results from this study strongly suggest that the polypeptides in HA1 arose from proteolysis of high molecular mass molecules. The studies also raise the possibility that immunologically related proteins in muscle and nonmuscle cells may be involved in linking actin filaments to Z-lines and membranes, respectively. PMID- 3095335 TI - Talin at myotendinous junctions. AB - Junctions formed by skeletal muscles where they adhere to tendons, called myotendinous junctions, are sites of tight adhesion and where forces generated by the cell are placed on the substratum. In this regard, myotendinous junctions and focal contacts of fibroblasts in vitro are analogues. Talin is a protein located at focal contacts that may be involved in force transmission from actin filaments to the plasma membrane. This study investigates whether talin is also found at myotendinous junctions. Protein separations on SDS polyacrylamide gels and immunolabeling procedures show that talin is present in skeletal muscle. Immunofluorescence microscopy using anti-talin indicates that talin is found concentrated at myotendinous junctions and in lesser amounts in periodic bands over nonjunctional regions. Electron microscopic immunolabeling shows talin is a component of the digitlike processes of muscle cells that extend into tendons at myotendinous junctions. These findings indicate that there may be similarities in the molecular composition of focal contacts and myotendinous junctions in addition to functional analogies. PMID- 3095339 TI - Abdominal aortic aneurysms. PMID- 3095338 TI - Relation between the regulation of DNA synthesis and the production of two secreted glycoproteins by 12-O-tetradecanoylphorbol-13-acetate in 3T3 cells and in phorbol ester nonresponsive 3T3 variants. AB - 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter, acts similarly to growth factors by selectively increasing the rate of production of the secreted proteins, mitogen regulated protein (MRP) and major excreted protein (MEP) by murine 3T3 cells. MRP, a 34 kilodalton (kDa) glycoprotein, is a member of the prolactin-growth hormone family of proteins. MEP, a 39 kDa glycoprotein, is a lysosomal thiol protease that is also secreted. The aim of our investigation was to determine the relation between increases in MRP and MEP production and the initiation of DNA synthesis in response to mitogens. The TNR-9 cell line is a variant of 3T3 cells in which growth factors, but not TPA and teleocidin, stimulate DNA synthesis and cell division. Using [35S]methionine to metabolically label proteins and SDS polyacrylamide gel electrophoresis to resolve the proteins, we found that growing cultures of 3T3 and TNR-9 cells responded equally well to TPA and teleocidin with increased rates of production of MRP and MEP. By contrast, the responses of quiescent TNR-9 cells to these tumor promoters in the increased production of MRP and MEP was greatly diminished compared with quiescent 3T3 cells. The changes in production of MRP in response to tumor promoters in quiescent and growing cells paralleled similar changes in the level of MRP mRNA. In summary, the ability to TPA and teleocidin to increase the rate of production of MRP and MEP correlated with the ability of these tumor promoters to stimulate DNA synthesis in quiescent 3T3 and TNR-9 cells. Evidently the biochemical condition that distinguishes TNR-9 from 3T3 cells and that limits the ability of tumor promoters to stimulate the production of MEP and MRP, and perhaps also DNA synthesis in TNR-9 cells occurs only when the cells are quiescent. PMID- 3095341 TI - Syncope in the elderly patient. PMID- 3095337 TI - Cytoplasmic myosin from Drosophila melanogaster. AB - Myosin is identified and purified from three different established Drosophila melanogaster cell lines (Schneider's lines 2 and 3 and Kc). Purification entails lysis in a low salt, sucrose buffer that contains ATP, chromatography on DEAE cellulose, precipitation with actin in the absence of ATP, gel filtration in a discontinuous KI-KCl buffer system, and hydroxylapatite chromatography. Yield of pure cytoplasmic myosin is 5-10%. This protein is identified as myosin by its cross-reactivity with two monoclonal antibodies against human platelet myosin, the molecular weight of its heavy chain, its two light chains, its behavior on gel filtration, its ATP-dependent affinity for actin, its characteristic ATPase activity, its molecular morphology as demonstrated by platinum shadowing, and its ability to form bipolar filaments. The molecular weight of the cytoplasmic myosin's light chains and peptide mapping and immunochemical analysis of its heavy chains demonstrate that this myosin, purified from Drosophila cell lines, is distinct from Drosophila muscle myosin. Two-dimensional thin layer maps of complete proteolytic digests of iodinated muscle and cytoplasmic myosin heavy chains demonstrate that, while the two myosins have some tryptic and alpha chymotryptic peptides in common, most peptides migrate with unique mobility. One dimensional peptide maps of SDS PAGE purified myosin heavy chain confirm these structural data. Polyclonal antiserum raised and reacted against Drosophila myosin isolated from cell lines cross-reacts only weakly with Drosophila muscle myosin isolated from the thoraces of adult Drosophila. Polyclonal antiserum raised against Drosophila muscle myosin behaves in a reciprocal fashion. Taken together our data suggest that the myosin purified from Drosophila cell lines is a bona fide cytoplasmic myosin and is very likely the product of a different myosin gene than the muscle myosin heavy chain gene that has been previously identified and characterized. PMID- 3095340 TI - Epidural and spinal opioids. PMID- 3095342 TI - The patient with a pigmented lesion. PMID- 3095343 TI - Diabetic neuropathies: practical clinical implications. PMID- 3095344 TI - A hospital employee with fluctuating jaundice. PMID- 3095345 TI - Hirsutism and polycystic ovary syndrome. PMID- 3095346 TI - Management of thyroid nodules: how far have we come? PMID- 3095347 TI - Acute severe asthma--the late-phase reaction and the continuing challenge. PMID- 3095348 TI - Gout and hyperuricemia: diagnosis and management. PMID- 3095349 TI - Medical intervention in a nuclear accident. AB - The medical care given to a victim of a radiation accident is one aspect of a larger emergency response that involves the establishment of control of the radiation source, prevention of secondary contamination of all persons having contact with the injured, organization of a general evacuation, and panic control. We have discussed the basic knowledge required to render medical care within the first few hours and days following an industrial nuclear incident. The fact that we have such knowledge should not be taken as an argument for the survivability of populations whose countries contemplate nuclear wars. At Chernobyl, radiation acutely injured about 300 persons and killed at least 31. And yet the enterprise needed to deal with the injured, the dying, and the evacuation of thousands taxed the medical resources of a superpower. Clearly, even the limited medical response available to physicians treating radiation victims rests on an infrastructure of facilities, equipment, drugs, transportation, communication, and organization that would surely be destroyed or severely incapacitated in a nuclear exchange. PMID- 3095351 TI - Hypoglycemia: doubts and realities. PMID- 3095350 TI - Better late than never. PMID- 3095352 TI - The 'great imitator' keeps up with the times. PMID- 3095353 TI - Polymicrobial bacteremia in a diabetic alcoholic. PMID- 3095354 TI - Mitral regurgitation and lateral Q waves. PMID- 3095355 TI - Echocardiography in ventricular and valvular disease I. PMID- 3095358 TI - Outpatient herniorrhaphy: pitfalls and precautions. PMID- 3095356 TI - Aggressive treatment of an aggressive disease. PMID- 3095357 TI - Urinary incontinence in the elderly. PMID- 3095360 TI - Psychological aspects of nonconvulsive status epilepticus in children. PMID- 3095359 TI - Emergency management of acute asthma. PMID- 3095361 TI - High-performance liquid chromatographic analysis of saturated monohydroxy fatty acid mixtures containing positional isomers of various chain-lengths. PMID- 3095362 TI - Thin-layer chromatography of some methylated amino acids with aqueous salt solutions used as eluents. AB - The retention order of methylated lysine and arginine derivatives followed a reversed-phase separation pattern on various silicas with aqueous salt solutions used as eluents. Principal component analysis established that the origin of the silica exerts a dominant influence on their chromatographic performance, and the effect of impregnation and salt quality are of secondary importance. Good linear correlations were found between the lipophilicity-decreasing effect of monovalent cations and their ionic radii. PMID- 3095363 TI - High-performance liquid chromatographic determination of 6,8-difluoro-1-(2 fluoroethyl)-1,4- dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid and its metabolites in laboratory animals. AB - A simple, sensitive and specific high-performance liquid chromatographic method for a new quinolone antimicrobial agent, 6,8-difluoro-1-(2-fluoroethyl)-1,4- dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid (AM-833, I), and its metabolites in serum and urine has been developed for their simultaneous determination. This method is based on ion-pair extraction and separation by ion pair reversed-phase chromatography with ultraviolet or fluorescence detection. The major metabolites in the serum and urine of mice, rats, dogs and monkeys were N-desmethyl I (compound II) and I N-oxide (compound III). Rabbit serum and urine contained N-desmethyl-3-oxo I (compound IV), 3-oxo I (compound V) and N-desmethyl 4-formyl I (compound VI) in addition to compounds I, II and III. Unchanged drug accounted for 80-90% of total serum concentrations in mice and more than 90% in rats, dogs and monkeys up to 6 h after dosing, whereas the fraction of compound I in rabbits was 34-67%. Unchanged drug was the most predominant in the urine of mice, rats, dogs and monkeys, whereas compound II was the most abundant in rabbit urine. Although rabbits and monkeys excreted 70-80% of dose in three-day urine, the total urinary excretion of mice, rats and dogs was relatively low, 40-50% of oral dose. The fraction of compound I in total urinary excretion was 63, 73, 27, 55 and 78% in mice, rats, rabbits, dogs and monkeys, respectively. These results suggest that there is a species difference in the metabolism and excretion pathway of compound I. PMID- 3095364 TI - Enzyme-linked immunosorbent assay with major outer membrane proteins of Brucella melitensis to measure immune response to Brucella species. AB - We developed an enzyme-linked immunosorbent assay (ELISA) system to measure human immunoglobulin G (IgG) and IgM response to the major outer membrane proteins of Brucella melitensis. The ELISA was more sensitive in detecting antibody than a standard microagglutination (MA) test with B. abortus antigen. Of 101 sera from persons with suspected brucellosis, 79 (78.2%) gave ELISA IgM titers greater than or equal to the B. abortus MA titer without 2-mercaptoethanol (2ME), which measures both IgM and IgG. Of the 101 sera, 97% gave ELISA IgG titers greater than or equal to the MA with 2ME titer. A total of 58 sera, drawn from 11 human patients from 1 to 29 weeks after onset of brucellosis, gave higher geometric mean titers for the ELISA IgG test than for the MA with 2ME test. These 58 sera also gave ELISA IgM geometric mean titers that were greater than or within one doubling dilution of the geometric mean titers of MA without 2ME. In addition to detecting antibody response to B. abortus, B. melitensis, and B. suis, the ELISA was sensitive to antibody response to human and canine infections with B. canis. The B. canis antibody response is not detected by the MA test with B. abortus antigen. The ELISA, with a standard preparation of major outer membrane proteins of B. melitensis as antigen, appears to be useful in measuring antibody response in humans to infections by all species of Brucella known to infect humans. PMID- 3095366 TI - Improved biochemical screening procedure for small clinical laboratories for vero (Shiga-like)-toxin-producing strains of Escherichia coli O157:H7. AB - Of 327 sorbitol-negative fecal isolates of Escherichia coli, 37 O157:H7 Vero (Shiga-like)-toxin-producing strains were identified. The specificity of the basic sorbitol screen was improved from 11.3 to 33.6% by the exclusion of organisms with negative ornithine and lysine decarboxylase reactions. PMID- 3095365 TI - Effect of medium and cultivation conditions on comparisons between latex agglutination and culture detection of group A streptococci. AB - In the laboratory diagnosis of pharyngitis, results from latex agglutination tests (LAT) performed directly on throat swabs are often compared with the isolation of group A beta-hemolytic streptococci (GABHS) from simultaneously obtained swabs cultivated on a variety of media under different atmospheric conditions. In this study, results of an LAT, Directigen, were compared with those of two different media: sheep blood agar (SBA) and group A selective strep agar (ssA). Specimens inoculated on SBA were incubated in three different atmospheres: air, 3 to 5% CO2, and anaerobically. Those inoculated on ssA were incubated in 3 to 5% CO2 only. Isolation of GABHS was confirmed by coagglutination. The standard for true positivity was the isolation of GABHS from at least one of the simultaneous cultures. Comparisons were made with samples from 693 adult patients. GABHS was isolated on at least one of the three cultures in 143 patients, demonstrating an isolation rate of 20.6%. LAT exhibited a sensitivity of 95.1%. SBA incubated in air, in CO2, or anaerobically had sensitivities of 86.2, 85.9, and 93.7%, respectively. The ssA detected 99.3% of the positive specimens. Single SBA culture proved to be inferior to LAT and therefore was a poor standard for measuring LAT performance. Single ssA cultures demonstrated the greatest sensitivity in GABHS detection and therefore could serve as a standard for measuring LAT performance. PMID- 3095367 TI - Comparison of methods for isolation and titration of Crimean-Congo hemorrhagic fever virus. AB - The fluorescence focus assay and the plaque assay in CER cells were compared with mouse inoculation for the isolation and titration of Crimean-Congo hemorrhagic fever virus. The fluorescence focus assay and the plaque assay were of similar sensitivity, but both produced 10- to 100-fold lower titers than did mouse inoculation. For specimens from 26 Crimean-Congo hemorrhagic fever patients in South Africa, virus was isolated from 20 by mouse inoculation and from only 11 by cell culturing. Although cell cultures were less sensitive for the isolation of virus from clinical specimens, they produced diagnostic results much more rapidly. PMID- 3095368 TI - Evaluation of a proprietary broth medium for microdilution susceptibility testing of nutritionally fastidious bacteria. AB - For microdilution susceptibility tests with nutritionally fastidious microorganisms, a new clear broth medium developed at Micro-Media Systems, Inc., Potomac, Md., was evaluated in a three-laboratory collaborative study. Replicate tests were performed with 80 isolates (51 Streptococcus spp., 27 Haemophilus influenzae isolates, and 2 Neisseria meningitidis isolates) against 15 antimicrobial agents. In standard 100-microliters volumes, results of tests in the new broth medium were comparable to those in the reference medium (Mueller Hinton broth with 2 to 3% lysed horse blood), but MICs were somewhat easier to read in the new broth medium. Results of similar tests in smaller panels, containing 40 microliters in each well, were less satisfactory; i.e., growth failures and poorly defined endpoints were more commonly encountered. With drugs other than erythromycin or clindamycin, the 40-microliters panels provided MICs which compared favorably with those obtained by standard reference methods. PMID- 3095369 TI - Laboratory diagnosis of mycobacterial infections in patients with acquired immunodeficiency syndrome. AB - Disseminated mycobacterial infections are commonly seen in acquired immunodeficiency syndrome (AIDS) patients, and laboratory culture is the best method for diagnosing these infections. In addition to conventional agar media, we used BACTEC 12A (Johnston Laboratories, Inc., Towson, Md.) broth medium for culture. More isolates of Mycobacterium avium complex and Mycobacterium tuberculosis were recovered from 12A broth than from Lowenstein-Jensen or Middlebrook 7H11 agar. Also, the average detection time of these mycobacteria was the earliest with 12A broth. Stool examination has been helpful in diagnosing mycobacterial disease in AIDS patients, and in this study both acid-fast stain and culture of fecal material was necessary for efficient detection of mycobacteria. Another sensitive and practical method for detecting mycobacterial infections in patients with AIDS is the Isolator lysis-centrifugation system (Du Pont Co., Wilmington, Del.) which offers the advantage of quantitating the degree of mycobacteremia. Laboratories should be alerted to the possibility of mixed mycobacterial infection in patients with AIDS, and positive cultures should be repeatedly examined to detect coinfection with a slower-growing mycobacterium such as M. tuberculosis as well as M. avium complex. PMID- 3095370 TI - Screening pneumococci for penicillin resistance. AB - Eighty-four pneumococci with various MICs of penicillin (38 with MICs of less than or equal to 0.06 micrograms/ml [susceptible], 35 with MICs of 0.12 to 1.0 micrograms/ml [relatively resistant], and 11 with MICs of greater than 1.0 micrograms/ml [resistant] ) were screened by a disk diffusion test using oxacillin and methicillin to see how well they distinguished penicillin susceptible strains from those with decreased susceptibility to penicillin. The effects of Mueller-Hinton agar plus 5% sheep blood and Trypticase soy agar plus 5% sheep blood and two atmospheres, ambient air and a candle extinction jar (increased CO2), were compared. There were no obvious differences between the effects of the two media, but zones were generally larger in ambient air than in increased CO2. Although the oxacillin test can separate penicillin-susceptible and -resistant strains, it cannot separate penicillin-resistant from relatively penicillin-resistant strains by using the breakpoint of less than 20 mm recommended by the National Committee for Clinical Laboratory Standards. When the 20-mm breakpoint was applied to methicillin, 12% of the relatively resistant strains tested were erroneously classified as susceptible. When different breakpoints were used for methicillin, there was better separation of the two classes of penicillin-resistant isolates, but a few relatively resistant strains were still classified as susceptible. We recommend that oxacillin, not methicillin, be used as the screening agent with Mueller-Hinton sheep blood agar and ambient air incubation and that the breakpoint be less than 20 mm to indicate resistance or relative resistance. PMID- 3095371 TI - Heating cells in acid methanol for 30 min without freeze-drying provides adequate yields of fatty acids and alcohols for gas chromatographic characterization of mycobacteria. AB - We studied the release of mycobacterial fatty acids (as methyl esters) and secondary alcohols after heating both wet and freeze-dried cells in methanolic hydrogen chloride for different time periods. A 30-min heating of the mycobacteria without prior freeze-drying was found adequate in a routine gas chromatographic procedure for strain and species characterization. PMID- 3095372 TI - Precipitating antibody against lipopolysaccharide of Haemophilus actinomycetemcomitans in human serum. AB - Approximately 6% of 50 tested human sera possessed precipitating antibody against lipopolysaccharide from Haemophilus actinomycetemcomitans (Actinobacillus actinomycetemcomitans). PMID- 3095374 TI - The Minnesota Plan for Nonsmoking and Health: the legislative experience. PMID- 3095373 TI - Comparison of enzyme-linked immunosorbent assay and radioimmunoprecipitation test for detection of immunoglobulin A antibodies to Mycoplasma pneumoniae in nasal secretions. AB - An immunoglobulin A (IgA) enzyme-linked immunosorbent assay was developed and compared with the radioimmunoprecipitation test in determinations of IgA antibodies to Mycoplasma pneumoniae. Of 45 nasal secretions obtained from infected volunteers, 42 (93.4%) were positive and 2 (4.4%) were negative in both tests. The IgA enzyme-linked immunosorbent assay is at least as sensitive as the IgA radioimmunoprecipitation test but is simpler and safer and should therefore be preferred. PMID- 3095377 TI - Cysts in pregnancy discovered by sonography. AB - The incidence of cysts in pregnancy was established with ultrasound. In 3,330 pregnant patients who underwent sonography, 38 adnexal cystic lesions (1.14%) were found. All but two cysts were discovered before 16 weeks. Follow-up showed that the majority of the cystic lesions resolved spontaneously; these were presumed to represent corpus luteum cysts. Five patients underwent surgery because of persistent cystic lesions; a mucinous cystadenoma, a benign cystic teratoma, a paraovarian cyst, an inclusion cyst, and a tuboovarian abscess were found. Septations and echogenic material were seen within the cystic teratoma and the tuboovarian abscess but the sonographic features of the other operated lesions were identical to those seen in the corpus luteum cysts. PMID- 3095378 TI - Ultrasonography of mediastinal teratoma. AB - We have studied real-time sonograms of 11 surgically proven benign mediastinal teratomas. Eight cystic teratomas were sonographically visualized as various kinds of masses: four complex, two solid, and two cystic. The echo patterns of cystic teratomas were determined by the serous or nonserous nature of the cysts. In the presence of serous fluid, the tumor was visualized as a cystic mass. If, on the other hand, the cyst of the tumor was nonserous or was sebaceous, it appeared as a solid or complex tumor. The remaining three solid teratomas, which had some small cysts, appeared as complex tumors. PMID- 3095379 TI - Computer analysis of echographic textures in Hashimoto disease of the thyroid. AB - Ultrasound B-scan images of the thyroid obtained from 10 patients with Hashimoto disease were digitized and processed by a computer method of image analysis that segments complex B-scan images into regions of homogeneous texture. The method was first applied to B-scan images of the normal thyroid and it consistently classified the normal tissue into a unique region. When applied to Hashimoto disease B-scan images, the same method segmented the thyroid into two regions. Detailed analysis of these regions revealed that their gray-level histograms were very different from that of the normal thyroid in eight cases. In two cases the histogram of one of the regions was similar to that of the previous eight cases, whereas the histogram and the tissue of the other region were similar to those of the normal tissue. This paper shows how these results can be interpreted according to the natural history of the Hashimoto disease. PMID- 3095375 TI - Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride rich lipoproteins by lipoprotein lipase in vivo. AB - Previous data suggest that apolipoprotein (apo) CIII may inhibit both triglyceride hydrolysis by lipoprotein lipase (LPL) and apo E-mediated uptake of triglyceride-rich lipoproteins by the liver. We studied apo B metabolism in very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL) in two sisters with apo CIII-apo AI deficiency. The subjects had reduced levels of VLDL triglyceride, normal LDL cholesterol, and near absence of high density lipoprotein (HDL) cholesterol. Compartmental analysis of the kinetics of apo B metabolism after injection of 125I-VLDL and 131I-LDL revealed fractional catabolic rates (FCR) for VLDL apo B that were six to seven times faster than normal. Simultaneous injection of [3H]glycerol demonstrated rapid catabolism of VLDL triglyceride. VLDL apo B was rapidly and efficiently converted to IDL and LDL. The FCR for LDL apo B was normal. In vitro experiments indicated that, although sera from the apo CIII-apo-AI deficient patients were able to normally activate purified LPL, increasing volumes of these sera did not result in the progressive inhibition of LPL activity demonstrable with normal sera. Addition of purified apo CIII to the deficient sera resulted in 20-50% reductions in maximal LPL activity compared with levels of activity attained with the same volumes of the native, deficient sera. These in vitro studies, together with the in vivo results, indicate that in normal subjects apo CIII can inhibit the catabolism of triglyceride-rich lipoproteins by lipoprotein lipase. PMID- 3095376 TI - Natural history of intrahepatic canine islet cell autografts. AB - We have serially followed the function of intrahepatic canine islet autografts in 15 beagle dogs for up to 24 mo. Of these, only 20% sustained normal levels of fasting blood glucose for greater than 15 mo posttransplant. Failure of autograft function was accompanied by a preferential loss of well-granulated beta cells in the engrafted islets. The chronic stimulation of an initially marginal intrahepatic beta-cell mass ultimately resulted in metabolic deterioration and loss of beta cells below the minimal threshold required to maintain normal fasting blood glucose levels. It is possible that transplantation of a larger mass of islets would result in indefinite graft function in dogs. However, it remains to be demonstrated in larger mammals, including humans, whether an islet cell mass that is initially adequate in a heterotropic site such as the liver can remain functionally competent over a prolonged period. PMID- 3095380 TI - Ruptured uterus: sonographic diagnosis. AB - Sonography was able to suggest a diagnosis of uterine rupture by demonstrating intra- or extraperitoneal hematoma in the correct clinical setting. A pelvic abscess complicating a uterine rupture was seen in one case. Previous uterine scar, use of prostaglandins for induction of labor, trauma with a currette, and cornual pregnancy were the implicated etiologic factors. Although the rupture site was never directly visualized by sonography, the combination of sonographic and clinical findings was strongly suggestive of the correct diagnosis. PMID- 3095381 TI - Cava-suprarenal line: new position for sonographic imaging of left adrenal gland. AB - Because of overlying attenuating structures, sonographic imaging of the left adrenal gland is often difficult, especially in obese or pediatric patients. In a series of 50 consecutive patients, the left adrenal glands were examined in both the conventional right posterior oblique (RPO) position and using the new cava suprarenal line (CSL) position. The CSL position permitted identification of the left adrenal gland in 90% of the patients; in contrast, the gland could be demonstrated in only 60% of the patients using the conventional RPO position. With the CSL position, the left adrenal gland could be imaged in half the time required with the conventional RPO position. The improved ability to demonstrate the left adrenal gland as well as the reduction in the required scanning time was particularly marked in obese and pediatric patients. PMID- 3095382 TI - Seminal vesicle abscess: diagnosis by transrectal ultrasound. PMID- 3095385 TI - Left upper quadrant pseudolesion secondary to normal variants in liver and spleen. PMID- 3095384 TI - Ultrasound as first imaging modality in superior mesenteric and portal vein thrombosis. PMID- 3095383 TI - Early prenatal diagnosis of cyclopia associated with holoprosencephaly. PMID- 3095386 TI - Intraoperative ultrasonographic diagnosis of Budd-Chiari syndrome. PMID- 3095388 TI - Role of ultrasound in obstetric management. AB - This is a retrospective, noncomparative study of the impact of routine and indicated ultrasound examinations on 163 private and 125 clinic patients, respectively. Management decisions (delivery, nonintervention, tocolysis) based on indicated ultrasound were made in 36.7% of the private and 63% of the clinic patients. Ultrasound was important in assigning and altering the EDC where dates were unsure. Serendipitous findings were especially important in finding fetal anomalies. Routine ultrasound provided the obstetrician with reassurance in normal pregnancies. PMID- 3095387 TI - Sonographic appearance of osteolysis of humeral head. PMID- 3095389 TI - Increased renal cortical echogenicity in pediatric renal disease: histopathologic correlations. AB - Retrospective comparisons between sonographic renal cortical echogenicity and the results of renal biopsies were made for 65 pediatric patients ranging in age from neonate to 18 years. There was a positive correlation between an increase in renal cortical echoes and interstitial infiltration as well as with glomerular obsolescence, tubular atrophy, and vascular changes. Since the sonographic changes were heterogeneous in origin, they are not specific. The sonographic findings also correlated positively with the clinical severity of disease. However, the heterogeneous origins of the sonographic finding and the absence of strong correlations indicate that gray-scale sonography cannot act as a prognostic index of the type or severity of disease in pediatric patients. PMID- 3095390 TI - Echocardiographic features of right atrial thrombi. AB - The clinical and echocardiographic features of six patients in whom a right atrial thrombus was detected using two-dimensional echocardiography are reported. In four patients with acute cor pulmonale, the thrombus appeared as a coiled mass moving freely within the right atrium and prolapsing through the tricuspid valve. In another patient referred for syncope, a large coiled mass attached to the lateral wall of the right atrium was seen prolapsing regularly through the tricuspid valve, simulating an atrial myxoma. In the remaining patient who presented with chronic cor pulmonale, two-dimensional echocardiography demonstrated a motionless ovoid mass with a broad base of attachment to the interatrial septum. PMID- 3095391 TI - Fetal cardiac arrhythmias and their effect on volume blood flow in descending aorta of human fetus. AB - Using a two-dimensional linear array real-time and pulsed Doppler ultrasound system, volume blood flow measurements were made in 86 normal pregnancies, seven cases of fetal bradycardia, and seven cases of fetal tachycardia at the lower thoracic level of the fetal descending aorta. During fetal cardiac arrhythmias, volume blood flow was maintained within the normal range until the heart rates reached around 50 bpm and 230 bpm, after which the volume blood flow diminished. The changes observed suggest that the Frank-Starling mechanism is functional in the fetal myocardium and demonstrate the stability of the fetal circulation. PMID- 3095393 TI - Ultrasound of normal skin. AB - The authors have used a commercially available real-time sector scanner and a 10 MHz probe with a built-in water path for B-mode imaging of the normal skin. Measurements have been performed in 10 volunteers at 18 sites on the body surface. Normal skin thickness ranges from 1.4 mm at the dorsal aspect of hand to 4.8 mm at the heel. Clinical applications of B-mode imaging of the skin are discussed. PMID- 3095392 TI - Failure of fluosol DA to enhance the ultrasonic image of infarcted myocardium. AB - The perfluorocarbon Fluosol DA has been reported to increase the subjective echogenicity of infarcted myocardium. To investigate this phenomenon, two dimensional echocardiograms were recorded in 20 closed-chest dogs before and 24,48,72, and 96 h following permanent coronary artery occlusion. Low-dose Fluosol, 10 ml/kg (LDF) (four dogs), high-dose Fluosol, 25 ml/kg (HDF) (eight dogs), or lactated Ringers 25 ml/kg (LR) (eight dogs) was administered 48 h after occlusion. Left ventricular sections corresponding to the short-axis echocardiographic examination plane were stained with nitroblue tetrazolium 48 h after Fluosol administration. Short-axis echocardiographic studies were evaluated by two blinded observers who found no consistent increase in the echogenicity of the infarcted area in any group. Videodensitometry of the infarcted area, normalized to the average value of two remote areas, confirmed mean post-Fluosol increases of 66% in LR dogs, 65% in LDF dogs, and 107% in HDF animals (p less than 0.001 for all dogs; all intergroup comparisons NS). The increase in videodensity observed in all groups may have occurred as a consequence of volume administration, although changes in infarct intensity occurring over time cannot be excluded. PMID- 3095394 TI - Prenatal diagnosis of arteriovenous malformation of the vein of Galen. PMID- 3095395 TI - Transrectal ultrasound diagnosis of a misplaced Foley catheter. PMID- 3095396 TI - Hydrops of the gallbladder in typhoid fever as demonstrated by sonography. PMID- 3095397 TI - Hemobilia: a cause of false-negative ductal dilatation. PMID- 3095398 TI - Prenatal diagnosis of multiple cardiac tumors presenting as an arrhythmia. PMID- 3095401 TI - Australia. PMID- 3095399 TI - Metastatic melanoma to the epididymis suspected on preoperative ultrasound. PMID- 3095400 TI - Screening of the bladder base and urethra using linear array transrectal ultrasound scanning. PMID- 3095402 TI - Lithium carbonate and tardive dyskinesia. PMID- 3095404 TI - Cost effectiveness of alcoholism treatment in partial hospital versus inpatient settings after brief inpatient treatment: 12-month outcomes. PMID- 3095403 TI - Multiple skin tumors of indeterminate cells in an adult. AB - An adult patient with multiple unusual histiocytic tumors of the skin is described. As shown by immunohistologic study, electron microscopy, and immunoelectron microscopy, the tumors represent circumscribed proliferations of the Langerhans cell-related indeterminate dendritic cells of the skin. This distinct cutaneous histiocytosis may represent a paraneoplastic syndrome. PMID- 3095405 TI - Health services: what might the future be? PMID- 3095406 TI - A bullous variant of Kaposi's sarcoma in an elderly female. AB - We report the case of Kaposi's Sarcoma (KS) in an elderly Italian female that has slowly progressed and evolved clinically with bullous formation. The skin biopsy was diagnostic of KS, showing the typical spindle cell formations, but at the same time showing a labyrinth-like collection of vessels that correlated with the bullous nature of the clinical lesions. Immunohistochemical staining for factor VIII antigens demonstrated strong reactivity of non-neoplastic blood vessel endothelium but virtually no staining of tumor cells. This is similar to the reactivity of normal lymphatic endothelial cells and supports the notion that these labyrinth-like vessels are derived from lymphatic endothelium. PMID- 3095409 TI - Metabolic adaptation in protein-energy malnutrition. AB - The metabolic response to chronic undernutrition covers a wide spectrum that ranges from decreased growth velocity in mild cases to profound distortion of body silhouette and composition and functional derangements in advanced stages of the protein-energy malnutrition-infection complex. A wide gamut of molecular, enzymatic, and hormonal processes assure a temporary availability of endogenous nutrients and the maintenance of vital functions. PMID- 3095407 TI - Necrotizing fasciitis precipitating diabetic ketoacidotic coma. AB - Necrotizing fasciitis is a rapidly spreading infection of the subcutaneous tissue and fascia; diabetes mellitus appears to be the most frequent underlying disease. Early diagnosis and immediate aggressive surgical therapy are paramount to curtail morbidity and mortality, but diagnosis is often difficult and unnecessarily delayed. We describe a case of necrotizing fasciitis precipitating diabetic ketoacidotic coma where correct diagnosis was not made until the 14th hospital day. We stress the fact that physicians caring for critically ill patients should be keenly aware of the possibility of necrotizing fasciitis when tending diabetic patients with unexplained fever; failure to recognize the disease can have devastating results. Finally, we believe this to be the first reported case of diabetic ketoacidotic coma precipitated by necrotizing fasciitis. PMID- 3095408 TI - Chelation and flotation in endodontic practice: an update. AB - The removal of broken instruments and silver points, as well as pulp tissue, may be accomplished by careful instrumentation, irrigation, and flotation. Flotation and recapitulation with smaller instruments and irrigation with copious amounts of sodium hypochlorite can clean out microorganisms and the organic matter from the tubular structure which provides a more ideal surface for sealing the root canal system. A sterile environment was obtained by removing the substrate and creating a more ideal environment for better healing. PMID- 3095412 TI - Mid-peripheral retinal hemorrhages. PMID- 3095413 TI - Ocular manifestations of Fabry's disease. AB - A 52-year-old black female teacher's aide presented for an eye examination with a complaint of progressively worsening vision, stinging and burning of the eyes, and occasional foreign body sensation. Examination revealed a dry eye syndrome and corneal dystrophy consistent with Fabry's disease, a cardiovascular disease with significant systemic as well as ocular findings. The patient was treated for the acute corneal symptoms and closely followed for progression of the dystrophic corneal changes. PMID- 3095411 TI - Geriatric grand rounds: nutrition and the elderly. University of California, Los Angeles. PMID- 3095410 TI - Direct in vivo evidence for mast cell degranulation during allergen-induced reactions in man. AB - There is little or no direct in vivo evidence in man to support the involvement of mast cell-mediator release in the pathogenesis of immediate allergic reactions. We have performed a within-subject controlled study to determine the changes that occur in nasal mast cells during allergen-induced rhinitis. Twelve subjects with asymptomatic rhinitis were studied. Nasal biopsy specimens were obtained from each subject after a control solution (isotonic saline, 0.9% w/v) had been nebulized into one nostril and allergen solution (freeze-dried allergen extract reconstituted with isotonic saline) into the other. The tissues obtained were fixed in Carnoy's solution and stained with the alpha-naphthol AS-D chloroacetate esterase reaction (N AS-D CA ER). Mast cells were counted under light microscopy in the epithelium and lamina propria, and the integrity of each cell was assessed. No significant differences were found in the number of epithelial or lamina propria mast cells in biopsy specimens obtained after saline or allergen administration. However, the number of degranulated mast cells after allergen provocation (89%) was significantly greater than after instillation of control solution (15%) (p = 0.003). Changes of mast cell degranulation after allergen provocation were confirmed by electron microscopy. In six nonatopic, control subjects without rhinitis, there was no significant difference between the percentages of degranulated mast cells after allergen provocation (25.8%) and instillation of saline (24.3%). This study provides direct in vivo evidence for allergen-induced mast cell activation in man. PMID- 3095414 TI - Effects of diflubenzuron on the mouse liver. AB - Diflubenzuron (DFB), a potent inhibitor of insect chitin synthesis, was administered to Swiss Webster mice in a 30-day oral intubation study. Animal groups received either no treatment, vehicle control (Polyethylene glycol 400), or DFB suspensions at doses of 125, 500, and 2,000 mg/kg body weight. Hepatic glutathione S-transferase activity as well as morphological characteristics were studied. DFB was shown to elicit hepatocellular changes at all dose levels. The activities of three glutathione S-transferases (S-aryl, S-aralkyl, and S-epoxide) were all altered after DFB administration. Light microscopy revealed radial arrays of hepatocellular vacuolization between the portal and central vein areas. Electron-microscopic examination, verified by morphometric analysis, revealed degenerative changes as well as an increased volume density of the endoplasmic reticulum. PMID- 3095415 TI - Age-related acceleration of glycation of tissue proteins in rats. AB - The Maillard reaction on proteins is a nonenzymatic glycosylation that is now termed glycation and produces a ketoamine linkage on the protein. The extent of this glycation was estimated by determining furosine (epsilon-N-(2-furoylmethyl) L-lysine), which is derived from glycated lysine residues. Glycation of rat sciatic nerve and aorta increased with advancing age for up to 50 weeks and the high degree of glycation was maintained thereafter. The level of hemoglobin did not change significantly after 14 weeks. These results suggest that tissue glycation may increase with aging and may be involved in the mechanism of aging. PMID- 3095416 TI - Basal serum prolactin levels and prolactin responses to constant infusions of thyrotropin releasing hormone in healthy aging men. AB - We measured serum prolactin (PRL) levels by RIA before and during a 240-min constant infusion of TRH (0.4 microgram/min iv) in three similarly sized groups of healthy aging men 30 to 49, 50 to 69, and 70 to 96 years. Basal data were evaluated by analysis of variance with Duncan's multiple range test and regression analysis. Mean basal serum PRL level was elevated (p less than .05) in the oldest group, attributable to PRL elevations (between 20 and 40 ng/ml) in 4 men over 75 years. Serum PRL levels decreased (p less than .001) from -30 min to 0 min before TRH infusion in all groups, but there was no age-dependent difference (p greater than .3) in the magnitude of the reduction. Repeated measures analysis of variance showed increased serum PRL levels (p less than .001) during TRH infusion in all age groups, and an age-dependent increase (p less than .05) in magnitude of peak PRL response. This significant difference was between the two oldest age groups early in the infusion. Chi-square analysis revealed an increased (p less than .05) frequency of early (less than 120 min) peak responses in the oldest age group. The present data suggest that basal and TRH-stimulated PRL secretion may be augmented in some healthy older men. PMID- 3095418 TI - Relocation and the elderly: changing perspectives. PMID- 3095417 TI - Infection. PMID- 3095419 TI - Dopachrome conversion and dopa oxidase activities in recessive yellow mice. Catalytic activities of extracts from pheomelanic and eumelanic tissues. AB - The dopa oxidase activity of tyrosinase and the dopachrome conversion activity of dopachrome oxidoreductase (dopachrome conversion factor) are reduced in skin or hair follicle extracts of pheomelanic mice compared with eumelanic mice. In this study, pheomelanic tissues are compared with eumelanic tissues of the same mice and found to be reduced in their DO and DC activities. Implications are discussed. PMID- 3095420 TI - Neonatal sympathectomy of normotensive Wistar-Kyoto and spontaneously hypertensive rats with 6-hydroxydopamine: effects on resistance vessel structure and sensitivity to calcium. AB - 6-Hydroxydopamine (6-OHDA) was injected on alternate days from birth to 3 weeks of age into spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) control rats. The effects of this neonatal treatment on cardiovascular structure and mesenteric resistance vessel calcium sensitivity was studied in young (6 week) and adult (5 month) rats. Mean arterial pressure of treated SHRs and WKYs was reduced by 10% compared with control rats, but the heart:body weight ratio was unaffected by treatment. Both pharmacological and histological studies suggested that at 6 weeks of age, mesenteric resistance vessels from treated WKYs were completely denervated, but that vessels from treated SHRs still had sparse innervation. At 5 months all vessels from the treated rats had some adrenergic innervation, but less than the control rats. In the WKYs, treatment was associated with reduced media:lumen ratio and reduced calcium sensitivity of the mesenteric resistance vessels, while no such changes were observed in the SHR vessels. The results indicate that the sympathetic nervous system in SHRs is more resistant to chemical denervation than the sympathetic nervous system of the WKYs. The results also suggest that sympathetic innervation of mesenteric resistance vessels may affect vessel structure and sensitivity. PMID- 3095422 TI - Recognition of MHC class I allodeterminants regulates the generation of MHC class II-specific CTL. AB - We have analyzed the signals influencing the generation of major histocompatibility complex (MHC) class II allospecific cytolytic T lymphocytes (CTL) and have found that the development of these CTL is actively regulated in primary in vitro cultures by Lyt-2+ T cells triggered in response to MHC class I alloantigens. Class II allospecific CTL can be readily stimulated in primary cultures, but the presence of a simultaneous class I MHC stimulus in these cultures causes a marked reduction of class II-specific CTL activation. This reduction can be prevented by adding to culture a dose of monoclonal anti-Lyt-2 antibody (in the absence of complement) that does not block the generation of class I-specific CTL. The role of MHC class I alloantigens in the regulation of class II allospecific responses illustrates that T cells recognizing class I and class II MHC antigens in mixed leukocyte cultures interact in a complex and nonreciprocal manner to influence the final effector T cell repertoire elicited by this complex immunogenic challenge. PMID- 3095421 TI - Accessory cell-T cell interactions involved in anti-CD3-induced T4 and T8 cell proliferation: analysis with monoclonal antibodies. AB - The effect of monoclonal antibodies (Mab) directed at T cell and accessory cell (AC) surface molecules on OKT3-induced T4 and T8 cell proliferation was examined. Mab directed at nonpolymorphic class I (W6/32, MB40.5) and class II (L243) major histocompatibility complex (MHC)-encoded gene products, an epitope common to LFA 1, CR3, and the p150, 95 molecule (60.3), and a heterodimer present on monocytes (M phi) and activated T cells (4F2) inhibited M phi-supported OKT3-induced proliferation of both T4 and T8 cells. Moreover, an Mab directed at the CD4 molecule (66.1) inhibited OKT3-induced T4 but not T8 cell proliferation, whereas an Mab directed at the CD8 molecule (OKT8) inhibited T8 but not T4 cell responses. With the exception of 66.1, each inhibited OKT3-induced T cell proliferation when added as late as 15 hr after the initiation of culture. Inhibition could not be explained by competition for Fc receptors on the AC. A variety of other Mab including OKT11 and those directed at other HLA-DR and DQ determinants were not inhibitory. The inhibitory Mab were found to diminish T4 cell IL 2 production and IL 2 receptor expression. Consequently, IL 2 reversed some but not all of the Mab-mediated inhibition of T cell proliferation. In contrast to the effects noted with M phi-supported responses, 60.3 and 66.1 but neither L243 nor 4F2 inhibited OKT3-induced T4 cell proliferation supported by Ia or IFN-gamma-treated Ia+ endothelial cells. None of the Mab tested inhibited T cell proliferation induced by the AC-independent stimuli OKT3 and phorbol myristate acetate (PMA) or calcium ionophore and PMA in the presence or absence of added AC. The data therefore suggest that the Mab inhibit OKT3-induced activation of T4 and T8 cells by preventing necessary interactions between AC and T cell surface proteins. Moreover, the results suggest that different arrays of interaction molecules are involved in OKT3-induced T cell proliferation depending on the nature of the AC and the responding T cell subset. PMID- 3095423 TI - Monoclonal antibodies, L-35 and L-36, define novel T cell activation antigens. AB - Two novel T cell specific activation antigens were characterized and were defined by monoclonal antibodies developed against mitogen-stimulated human T cells. These antigens, designated as L-35 and L-36 were expressed on both the CD 4(Leu 3) and the CD 8(Leu-2) subsets of activated but not resting T cells. Moreover these antigens were not expressed on a number of T, B, and myeloid tumor cell lines. L-35 and L-36 were expressed on interleukin 2 (IL 2)-dependent cloned T cell lines, and were weakly expressed on the T cell tumor line, HSB-2. L-35 was expressed on granulocytes and a small subset of thymocytes. SDS-PAGE analysis of 125I-labeled lysates from phytohemagglutinin (PHA)-activated T cells demonstrated that L-35 existed as a complex of 32,000 and 97,000 dalton polypeptides under reducing and nonreducing conditions. Anti-L-36 immunoprecipitated a 90,000 dalton structure from PHA-activated cell lysates prepared with CHAPS detergent. When immunoprecipitates were analyzed from [35S]methionine labeled lysates, anti-L-35 precipitated only the 97,000 dalton component, suggesting that the 32,000 dalton subunit of L-35 complex was not synthesized by the activated cell population. Furthermore anti-L-35 did not immunoprecipitate a 32,000 dalton component from 125I-labeled lysates of anti-Leu-4 or Con A-activated cells, suggesting that the 32,000 dalton component of the L-35 complex may represent a subunit of PHA. The 32,000 dalton protein could not, however, be precipitated from cells incubated with PHA for less than 1 day. These results suggested that anti-L-35 recognizes a 97,000 dalton structure expressed on activated T cells, and that upon activation by PHA, becomes associated with a subunit of this mitogen. PMID- 3095425 TI - Characterization of an anti-peptide antibody that recognizes the murine analogue of the human T cell antigen receptor-T3 delta-chain. AB - The T cell antigen receptor consists of two disulfide-linked 40,000 to 45,000 dalton glycoproteins (alpha and beta) that contain variable and constant regions analogous to those found in immunoglobulin molecules. The antigen receptor on murine T cells is noncovalently associated with four additional nonpolymorphic structures. We describe an antibody that binds one of these molecules, a 26,000 dalton glycoprotein homologous to the human T3 delta-chain. This antibody immunoprecipitates the entire antigen receptor complex from a T cell hybridoma and from normal murine thymocytes. It represents the first reagent that can immunoprecipitate the antigen receptor complex on all murine T cells. PMID- 3095424 TI - Abrogation of hybrid resistance to bone marrow engraftment by graft-vs-host induced immune deficiency. AB - Lethally irradiated F1 mice, heterozygous at the hematopoietic histocompatibility locus Hh-1, which is linked with H-2Db, reject bone marrow grafts from H-2b parents. This hybrid resistance (HR) is reduced by prior injection of H-2b parental spleen cells. Because injection of parental spleen cells produces a profound suppression of F1 immune functions, we investigated whether parental induced abrogation of HR was due to graft-vs-host-induced immune deficiency (GVHID). HR was assessed by quantifying engraftment of H-2b bone marrow in F1 mice with the use of splenic [125I]IUdR uptake; GVHID, by the ability of F1 spleen cells to generate cytotoxic T lymphocytes (CTL) in vitro. We observed a correlation in the time course and spleen cell dose dependence between loss of HR and GVHID. Both GVHID and loss of HR were dependent on injection of parental T cells; nude or T-depleted spleen cells were ineffective. The injection of B10 recombinant congenic spleens into (B10 X B10.A)F1 mice, before grafting with B10 marrow, demonstrated that only those disparities in major histocompatibility antigens that generated GVH would result in loss of HR. Thus, spleens from (B10 X B10.A(2R]F1 mice (Class I disparity only) did not induce GVHID or affect HR, whereas (B10 X B10.A(5R))F1 spleens (Class I and II disparity) abrogated CTL generation and HR completely. GVHID produced by a class II only disparity, as in (B10 X B10.A(5R))F1 spleens injected into (B6bm12 X B10.A(5R))F1 mice, was also sufficient to markedly reduce HR to B10 bone marrow. This evidence that GVHID can modulate hematopoietic graft rejection may be relevant to the mechanisms of natural resistance to marrow grafts in man. PMID- 3095426 TI - Metabolism of 5-hydroxyicosatetraenoate by human neutrophils: production of a novel omega-oxidized derivative. AB - Human neutrophils incorporated 5-hydroxy-E,Z,Z,Z-6,8,11,14-eicosatetraenoic acid (5-HETE) into cellular triglyceride and phospholipid. They also metabolized 5 HETE into a novel, extracellularly released derivative, 5,20-dihydroxy-E,Z,Z,Z 6,8,11,14-eicosatetraenoic acid (5,20-diHETE). 5,20-diHETE formation predominated at higher substrate concentrations and longer incubation intervals. In the absence of added 5-HETE, 1 X 10(8) neutrophils stimulated with 20 microM ionophore A23187 produced up to 243 ng of 5,20-diHETE, indicating that both endogenously formed and exogenously added substrate could be oxidized at carbon 20. 5,20-diHETE was about 10- to 100-fold weaker than 5-HETE in enhancing human neutrophil degranulation responses to platelet-activating factor. omega-Oxidation appears to be a general enzymatic mechanism for inactivation of arachidonic acid metabolites. PMID- 3095427 TI - Enhancement of human eosinophil cytotoxicity and leukotriene synthesis by biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor. AB - Culture medium conditioned by activated human T lymphocytes enhances the in vitro cytotoxicity of purified human eosinophils toward Schistosoma mansoni larvae, suggesting the existence of a mechanism for T lymphocyte regulation of eosinophil function. Here we show that purified biosynthetic (recombinant) human T lymphocyte granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced markedly two eosinophil functions: cytotoxicity toward schistosomula by a mean of 676%, and calcium ionophore A23187-induced generation of leukotriene C4 (LTC4) by a mean of 135%. Augmentation of each eosinophil function by GM-CSF was time- and dose-dependent, with a dose-response relationship at concentrations between 1 and 20 pM. Tumor necrosis factor (TNF) enhanced eosinophil cytotoxicity with slower kinetics, a different dose-dependence relationship, and to a lower maximum, as compared with GM-CSF. There was no detectable effect of TNF on calcium ionophore A23187-induced generation of LTC4. The effect of GM-CSF on arachidonic acid metabolism to LTC4 reached a plateau with 60 min of incubation before stimulation with ionophore, and was characterized by an initial augmentation of the intracellular level of LTC4 and a subsequent increment in extracellular LTC4. Thus, GM-CSF can serve as a mediator for T lymphocyte regulation of functions of mature eosinophils. It is also the first defined macromolecule known to enhance metabolism of membrane-derived arachidonic acid via the 5-lipoxygenase pathway. PMID- 3095428 TI - Regulation of class II gene expression: analysis in B cell stimulatory factor 1 inducible murine pre-B cell lines. AB - We have analyzed the mechanism of action of BSF-1 on class II gene expression in two murine pre-B cell lines that are at different stages of differentiation. In vitro transcription assays demonstrated that BSF-1 induced rapid transcription of class II genes within 1 hr by a mechanism that was independent of protein synthesis. Although cell surface expression of class II was detectable by 2 hr after induction and persisted for up to 96 hr after removal of BSF-1, levels of class II-specific mRNA and density of cell surface class II increased to a maximum between 24 and 72 hr after induction. Furthermore, prostaglandin E2 prevented the induction of class II gene expression by BSF-1. The effects of BSF 1 are unlikely to be mediated through calcium fluxes or activation of protein kinase C, since treatment with agents such as PMA and the calcium ionophore A23187 did not result in expression of class II molecules. Other lymphokines, such as IFN-gamma, IL 1, IL 2, and IL 3, did not affect class II gene expression in these two cell lines. These data provide further insight into the mechanisms by which class II gene expression is regulated in B cells. PMID- 3095431 TI - Cryopreservation and short-term storage of human lymphocytes for surface marker analysis. Comparison of three methods. AB - Three methods were compared for the cryopreservation and short-term storage of human lymphocytes for cell surface marker analysis with monoclonal antibodies and flow cytometry. These methods were controlled-rate freezing followed by storage in liquid nitrogen (CR), direct placement into liquid nitrogen (LN), and direct placement at -70 degrees C (-70). Our findings show that the LN and -70 methods of cryopreserving lymphocytes are as effective as the CR method for the purpose of determining T cell and large granular lymphocyte subsets within 1 month after freezing. PMID- 3095430 TI - Analysis of deficiencies in IFN-gamma-mediated priming for tumor cytotoxicity in peritoneal macrophages from A/J mice. AB - The functional and biochemical responses of macrophages derived from the A/J mouse strain to IFN-gamma have been studied. As compared to macrophages obtained from C57BL/6 strain mice, cells from mice of the A/J strain are deficient in their response to IFN-gamma for acquisition of tumoricidal competence. This deficiency was not due to reduced expression of surface receptors for IFN-gamma or to altered affinity of the receptor for its ligand. IFN-gamma recently has been shown to enhance the potential activity of protein kinase C (PKc) and to modulate the efflux of intracellular Ca2+ in macrophages from C57BL/6 mice. Neither of these two biochemical changes were induced in macrophages derived from A/J mice. Functional competence could, however, be pharmacologically induced in both C57BL/6- and A/J-derived macrophages by combined treatment with an ionophore plus phorbol myristic acetate, which increase intracellular Ca2+ and stimulate PKc, respectively. Although the exact nature of the deficit in A/J strain mice has not been defined, the present findings indicate that it lies between the expression of receptor and the modulation of PKc activity and Ca2+ levels. Furthermore, the data provide support for the notion that these molecular changes are important components of the stimulus-response coupling process in IFN-gamma mediated activation of macrophages. PMID- 3095432 TI - Molecular calibration in flow cytometry with sub-attogram detection limit. AB - A monoclonal antibody to complement receptor type 1 (CR1) has been double labelled with 125iodine and fluorescein isothiocyanate (FITC) and used for parallel radioimmune assay (RIA) and flow cytometric studies. Serial dilutions of the reagent with unlabelled antibody were used to obtain a linear correlation between radioactivity counts and fluorescence over the whole range of labelled antibody molecules bound per cell, namely 700-25,000. This has enabled us to calibrate our flow cytometer in terms of numbers of molecules per channel as opposed to the customary arbitrary fluorescence units. Normal human granulocytes from a single donor were found to have a mean of 25,000 CR1 molecules per cell with a normal distribution and standard deviation of 4775 molecules. The detection limit of the flow cytometer was 730 CR1 molecules per cell which is equivalent to between 125 and 150 molecules of free fluorescein. This represents less than 0.1 attogram (ag) of fluorescein per cell, where 1 ag = 10(-18) g. The resolution was 44 CR1 molecules per digitization step of the analogue-to-digital converters (ADC) which corresponds to the fluorescence from less than ten molecules of free fluorescein. PMID- 3095429 TI - Endocytosis of MHC molecules by B cell-B lymphoma and B cell-T lymphoma hybrids. AB - Different cells and different cell surface determinants of the same cells take up liposomes, bound to them via monoclonal antibodies, with variable efficiency. We have previously reported that T and B lymphocytes differ in the extent to which they take up liposomes bound to MHC class I molecules; T cells endocytose class I molecules rapidly, but B cells endocytose class I molecules much less efficiently, although their endocytosis of class II molecules is rapid. An approach toward understanding the molecular basis for this difference was made by evaluating the internalization patterns of somatic cell hybrids of B and T cells. Hybrid cells were constructed between LPS-stimulated purified B cell blasts from C57BL/6 mice (H-2b) and the HAT-sensitive AKR T lymphoma BW 5147 (H-2k). Hybrids between the BALB/c B lymphoma M12.4.1 (H-2d) and B cell LPS blasts from B10.BR (H 2k) mice were also evaluated. In all cases, for hybrid tumor cells, liposomes that were bound to class I molecules encoded by genes from the B cell donor were endocytosed as efficiently as liposomes bound to the class I molecules of the recipient lymphoid cell. T cell tumors efficiently internalized their own class I molecules and those donated by B cells; B cell tumors internalized liposomes that were bound to their own and the donor B cell class I molecules poorly. Thus, our results suggest that the internalization of an MHC molecule is not an intrinsic property of the molecule, but rather of the cell in which it is found. PMID- 3095433 TI - Enzyme-linked immunosorbent assay (ELISA) for the detection and differentiation of Clostridium botulinum toxins type A and B. AB - Affinity chromatography has been used for a two-step purification of commercial horse botulinum antitoxic globulins type A and B. The first step performed using CH-Sepharose 4B conjugated to toxin type A (or B), permitted the removal of non botulinal antibodies from antitoxic globulin type A (or B). The anti-botulinal antibodies obtained from the first step were cross-absorbed in the second affinity chromatography using CH-Sepharose 4B conjugated to toxin B (for the purification of antibodies to type A) or to toxin A (for antibodies to type B). The antibodies obtained were used to coat polystyrene wells in an ELISA for the detection of botulinum toxin type A and type B. The first purification step increases the sensitivity of such an ELISA whereas the second step improved the specificity of the test. Only slight cross-reactions were observed between the type A and type B detection systems. The sensitivity achieved with ELISA was 100 and 300 DLM (dosis lethalis minima) for type A and B respectively. PMID- 3095435 TI - Lack of a requirement for the Fc region of IgG in restoring pneumococcal opsonization via the alternative complement pathway in sickle cell disease. AB - Children with sickle cell disease have reduced serum opsonization of Streptococcus pneumoniae. Our previous studies have suggested that opsonization mediated by both the alternative and classic complement pathways is reduced because of a deficiency of IgG antibodies to pneumococcal capsular polysaccharide. This study compares the ability of purified IgG (fractionated from goat antiserum to pneumococcal capsular polysaccharide) and F(ab')2 fragments of the IgG preparation to restore alternative pathway-mediated opsonization of S. pneumoniae to sera from patients with sickle cell disease. Both the whole IgG preparation and F(ab')2 fragments of this preparation restored opsonization to normal levels and concomitantly increased alternative pathway mediated deposition of C3 onto the pneumococci to a supranormal level. These results suggest that enhancement of opsonization is mediated by the F(ab')2 region of IgG antibody to capsular polysaccharide and is associated with an increase in complement deposition on the bacterial surface. PMID- 3095434 TI - Study of HLA-DR synthesis in cultured human keratinocytes. AB - Within the normal human epidermis only Langerhans and indeterminate cells express HLA-DR. Human keratinocytes (HK), however, may also express HLA-DR in certain disease states characterized by mononuclear cell infiltrates. Previous studies have shown that HK synthesize HLA-DR in response to stimulation by interferon gamma (INF-gamma). The purposes of this study were to define conditions under which cultured HK might express HLA-DR and to compare the HLA-DR synthesis of HK with that of monocytes. HLA-DR expression by HK as determined by indirect immunofluorescence of HK cultures was absent under standard low calcium conditions and remained absent with the addition of calcium, serum, mitogens, and supernatants from Pam-212 cells containing epidermal thymocyte-activating factor. HLA-DR expression in HK was induced by cocultivation with concanavalin A stimulated peripheral blood mononuclear cells (PBMC), but not unstimulated PBMC. This effect was time-dependent and directly related to the number of PBMC. HLA-DR expression was also induced in a time- and dose-dependent manner by addition of supernatant from stimulated PBMC (SS) or by addition of recombinant INF-gamma but not by addition of interleukin (IL)-1 or IL-2. Induction by either SS or INF gamma was blocked by an antiserum to INF-gamma. As determined by a semiquantitative immunoprecipitation technique, HLA-DR synthesis by HK was directly related to INF-gamma concentration. The pattern of HLA-DR peptides produced by HK was similar to that of monocytes, but the relative quantity synthesized was far less than that of monocytes. PMID- 3095436 TI - Neutralization and lipoprotein binding of lipopolysaccharides in tolerant rabbit serum. AB - We examined the ability of sera drawn from rabbits made tolerant to lipopolysaccharide (LPS) from Escherichia coli O18 to inhibit heterologous LPS induced gelation of Limulus lysate. Compared with a pool of pretolerant sera, a pool of tolerant sera from these rabbits neutralized 5.5-fold more LPS from Salmonella typhimurium, 4.9-fold more LPS from Pseudomonas aeruginosa, and 10.0 fold more LPS from Klebsiella pneumoniae. Because previous studies have found that LPS bound to lipoprotein is less toxic than unbound LPS, we also studied the binding of LPS lipoprotein fractions in the serum pools by using fractionation with a cesium chloride-equilibrium density gradient. Radiolabeled LPS from E. coli O113 bound much more rapidly to lipoprotein fractions in tolerant serum than in pretolerant serum (after 11 min of incubation, 66.1% vs. 16.5% binding, respectively). PMID- 3095438 TI - Laboratory-acquired meningitis caused by Brucella abortus strain 19. PMID- 3095437 TI - Prospective study of catheter replacement and other risk factors for infection of hyperalimentation catheters. AB - To determine risk factors for infection of hyperalimentation catheters, we prospectively studied 169 catheter systems (88 patients) by using a semiquantitative culture technique. Infection occurred in 24 (14%) catheters (16 patients), was inversely proportional to the number of previous catheters inserted by the operator (P less than .02), and was proportional to the interval between admission and catheter insertion (P less than .0005). Catheter replacement over a guidewire was no more likely to be associated with infection than was a de novo percutaneous insertion at another site (P = .6). Using a proportional hazards model, we estimated the risk of infection per day to be 1.3 times greater for a catheter if the patient had been hospitalized 50 days instead of seven days, and 3.8 times greater if the patient had a Swan-Ganz catheter at the time of insertion. PMID- 3095439 TI - Listeria monocytogenes cholecystitis. PMID- 3095440 TI - Determination of the complete amino acid sequence of recombinant human gamma interferon produced in Escherichia coli. AB - The complete amino acid sequence of recombinant human gamma-interferon (HuIFN gamma) produced in Escherichia coli was determined using a gas-phase protein sequencer. The sequence was established by automated Edman degradation on the intact protein and its peptides obtained after Staphylococcus aureus V8 protease or trypsin digestion. The result was identical to the amino acid sequence predicted from the nucleotide sequence of the cloned HuIFN-gamma cDNA except that it was missing the four carboxy-terminal residues, Arg-Ala-Ser-Gln. PMID- 3095441 TI - Induction of tryptophan degradation in vitro and in vivo: a gamma-interferon stimulated activity. AB - Human recombinant gamma interferon (rHuIFN-gamma) was found to induce tryptophan degradation in vitro in human cell cultures and in vivo in participants in phase I clinical trials. When human lung fibroblasts were treated with various concentrations of rHuIFN-gamma, they degraded tryptophan in a dose- and time dependent manner. No tryptophan degradation was observed when cells were incubated in growth medium alone or in medium supplemented with human recombinant beta-interferon (rHuIFN-beta ser). Similarly human bladder carcinoma cells were induced to catabolize tryptophan after incubation with rHuIFN-gamma, but no activity was observed in untreated cells or cells treated with either rHuIFN-beta ser or human naturally produced alpha-interferon (HuIFN-alpha). When tryptophan plasma levels were measured in cancer patients who had received i.v. bolus injections of rHuIFN-gamma as part of a phase I clinical trial, decreased tryptophan levels were observed when compared with pretreatment values or values obtained from individuals who had received i.v. injections of HuIFN-alpha. Urine analyses were suggestive that plasma tryptophan degradation occurred via the kynurenine catabolic pathway in individuals who received rHuIFN-gamma. We conclude that tryptophan degradation is an activity induced in vitro and in vivo in response to exogenous IFN-gamma but not to IFN-alpha or IFN-beta. Tryptophan degradation may play an important role in the mechanism of antiproliferative, immunologic, and clinical side effects of IFN-gamma. PMID- 3095442 TI - Nonidentical induction of the guanylate binding protein and the 56K protein by type I and type II interferons. AB - Upon the addition of interferon (IFN) to cultured human cells, the expression of genes encoding the 56K and the guanylate binding protein (GBP) is specifically induced. We have analyzed their expression at the protein and the mRNA levels and studied how their regulation differs in cells treated with different IFNs. In the type I IFN (alpha and beta)-treated cells, we detected the accumulation of the 56K protein primarily in the cytoplasm. The 56K protein was undetectable in untreated cells or in cells treated with type II IFN (IFN-gamma). In contrast, a greater amount of GBP was synthesized in cells treated with type II IFN than in cells treated with type I IFN. The differential induction of these two proteins correlates well with the relative amounts of their mRNAs in type I and type II IFN-treated cells. In addition, the IFN-induced synthesis of the 56K protein was found in certain cell lines in which the GBP synthesis was not detected. These results suggest that the regulation of these two genes requires dissimilar factors which are activated or induced to different extents by type I and type II IFNs. PMID- 3095443 TI - Synergistic effects of HuIFN-gamma on 2',5'-oligoadenylate synthetase induction by HuIFN-alpha. AB - Human skin fibroblast cells were treated with three types of human interferon (HuIFN), alpha, beta, and gamma separately, and in series of combinations at different concentrations. The IFN-induced enzyme, 2',5'-oligoadenylate (2-5A) synthetase, which is thought to be mediating the major part of the antiviral activity, was measured subsequent to 24 h treatment. The HuIFN-gamma potentiated the induction of 2-5A synthetase elicited by either HuIFN-alpha or HuIFN-beta, but the effect was seen only at low levels, i.e., 1-10 units. At higher levels, an antagonistic effect was seen. The individual subspecies of the HuIFN-alpha from native HuIFN-alpha were purified, separated, and analyzed for their ability to induce antiviral activity in human and bovine cells together with their capacity to induce 2-5A synthetase. Of the 12 species with molecular weights between 16,950 and 22,900 daltons, one species (MW 21,800) exerted peculiar properties in that it protected human cells better than bovine--at the same IFN level--and, it induced more 2-5A synthetase in human cells than in bovine cells. PMID- 3095444 TI - [Frequency and microbiological characteristics of toxic shock syndrome toxin-1 producing Staphylococcus aureus from the vaginal fluor]. PMID- 3095445 TI - [Restoration by N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutamine)-N epsilon stearoyl-L-lysine from the decomplement state in mice induced by cobra venom factor, followed by acquisition of resistance to bacterial infections]. PMID- 3095446 TI - [Enterobacter bacteremia: clinico-bacteriological study of 27 patients]. PMID- 3095447 TI - [Serotype and antibiotic susceptibility of Staphylococcus aureus and Pseudomonas aeruginosa isolated from burn patients, with special reference to hospital infection]. PMID- 3095448 TI - [Relationship between sepsis and intestinal flora in immuno-compromised children]. PMID- 3095449 TI - [Bacteriological study of preparations of multi-drug resistant, lactic acid bacteria--viable cell numbers, drug-resistance and stability of the organisms]. PMID- 3095450 TI - [Antigenicity of Japanese encephalitis virus passaged serially in chick embryo cell cultures]. PMID- 3095451 TI - [Study on the contaminating antigen in purified mumps virus antigen from the allantoic fluid of hen's eggs for enzyme-linked immunosorbent assay (ELISA)]. PMID- 3095452 TI - [A case of purulent meningitis caused by Listeria monocytogenes type 4c]. PMID- 3095453 TI - [Two cases of Campylobacter fetus meningitis]. PMID- 3095454 TI - [Density and distribution of C. tetani in the ground]. PMID- 3095455 TI - [Therapeutic effect of vancomycin hydrochloride, a nonabsorbable antibiotic, on intractable (lactulose resistant) chronic hepatic encephalopathy in cirrhotic patients]. PMID- 3095456 TI - [Clinico-bacteriological study of diarrhea caused by Campylobacter fetus subsp. fetus]. PMID- 3095457 TI - [Biotyping of Campylobacter jejuni isolated from diarrhea patients]. PMID- 3095458 TI - [Enhancement of virulence in experimental mixed infection with Escherichia coli and Klebsiella pneumoniae, or Pseudomonas aeruginosa in mice]. PMID- 3095459 TI - [Studies of Pasteurella multocida, isolated from the surgical materials of zoonoses and oral swabs from pets]. PMID- 3095460 TI - [In vitro antibacterial activity of norfloxacin (NFLX) against enteritis-causing bacteria]. PMID- 3095461 TI - [Detection of serum Candida antigen by an enzyme-linked immunosorbent assay with the avidin-biotin system--(1). Method and basic studies]. PMID- 3095462 TI - [Comparative study of MK-0787/MK-0791 and piperacillin in respiratory tract infections]. PMID- 3095463 TI - [The usefulness of Chlamydiazyme for the diagnosis of Chlamydia trachomatis infection in the genito-urinary tract]. PMID- 3095464 TI - [Analysis of lymphocyte subsets in the peripheral blood in patients with Mycoplasma pneumoniae pneumonia]. PMID- 3095465 TI - [Studies on oral-adjuvant chemotherapy of uterine cervical cancer after surgical treatment]. AB - To improve the postoperative survival rate of patients with cervical cancer, those with clinical stage Ib or above were treated with adjuvant chemotherapy (oral Tegafur). The drug sensitivity of cultured cervical epidermoid cancer cells was tested with 5-fluorouracil (5-FU), an active derivative of Tegafur. The cumulative rate of recurrence of the group treated with adjuvant chemotherapy was 28.4% (19/67 cases), significantly lower than that of the untreated control group 69.8% (44/63 cases) (p less than 0.01). The rate of recurrence for the two groups was evaluated with Cox's regression models. The rate of recurrence of the treated group was about 50% that of the untreated group. The drug sensitivity of the cultured cancer cells was investigated with a colony forming assay, and a dose response curve was obtained for the time-dependent anticancer drug. The inhibition of DNA synthesis peaked after 24 to 72 hours of incubation with 5-FU at 0.1 to 0.5 micrograms/ml, but the peak appeared in 4 to 8 hours at 1.0 to 10.0 micrograms/ml. Morphologic changes occurred after 192 hours of incubation at 0.1 microgram/ml. Investigation of the drug sensitivity by cell kinetics disclosed prolongation of the cell cycle after 144 hours at 0.1 microgram/ml and inhibition of cell cycle progression after 48 hours at 10.0 micrograms/ml. Thus, adjuvant chemotherapy with Tegafur reduces the rate of recurrence to about 50% in postoperative patients with cervical cancer. This finding was also supported by an experimental study. PMID- 3095466 TI - [Automated fetal heart rate analysis and its trendgram in relation to gas analysis and acid-base balance of umbilical cord arterial blood]. AB - The gas analysis and acid-base balance of the umbilical cord arterial blood of 108 newborn infants were compared with the results of the automated analysis of the intrapartum fetal heart rate (FHR) and its trendgrams. The parameters of the automated analysis of the FHR, which consisted of fetal distress (FD) index, uterine contraction area, FHR score, number of dips, baseline heart rate, variability amplitude and lag time, were shown on the trendgram every 5 minutes using a microcomputer. 1) The mean pH, BE and HCO3- of the 4 groups, that showed 0, 1, 2 and 3 or more on the FD index, were gradually decreased as the FD index was increased. 2) The FHR score, that was accumulated for 10 minutes from 0-10 minutes to 50-60 minutes prior to the birth, was well correlated with the umbilical cord arterial blood pH (r = -0.47), BE (r = -0.60) and HCO3- (r = 0.45). 3) The intrapartum trendgrams were classified into the normal and ominous groups on the basis of the FHR score and FD index. The differences between the respective mean pH, BE, HCO3-, PO2 and PCO2 for these groups were highly significant. 4) The specificity and the sensitivity of the trendgram were more than 70% in the prediction of a pH value lower than 7.25 and of a BE value lower than -6.0 mEq/l. PMID- 3095467 TI - Experimental study on the hemodynamics of the neonatal brain. AB - The effects of inhalation of different gases were studied in neonatal rabbits with the following results: In neonates with normal heart rate (HR), hyperoxia induced by O2 inhalation did not appreciably affect HR, but it increased cerebral tissue PO2, while decreasing cerebral blood flow (CBF). In many of those which fell into a state of marked bradycardia, not only HR and CBF but also cerebral tissue PO2 levels were recovered as a result of O2 inhalation. CBF was increased even when HR was hardly changed (at least when the HR decrease was 10% or less) by hypercarbia due to inhalation of CO2 mixed air. Severe hyperoxia induced by N2O inhalation caused bradycardia and reduced CBF. PMID- 3095468 TI - Microvascular anastomosis with a low-output carbon dioxide (CO2) laser. I. Laser device, techniques and conditions of anastomosis. AB - A low-output carbon dioxide laser was tentatively fabricated and applied to facilitate microvascular anastomosis. The femoral arteries and veins of Wistar albino rats were end-to-end anastomosed by either irradiating with a CO2 laser or the conventional technique of manual suturing. The CO2 laser was used at a power level of 21-40 mW and an exposure time of 5-15 sec. The patency rate was 96.2% for arteries and 92.6% for veins with the laser technique, while it was 97.6% for arteries and 78.0% for veins with the conventional technique. There was no significant difference between these two techniques in the patency rate of arteries, however, veins showed a significantly higher rate with the laser technique than with the conventional technique. The main advantages of the laser technique are that it is easier to perform and less time-consuming than the conventional technique of manual suturing. PMID- 3095469 TI - Microvascular anastomosis with a low-output carbon dioxide (CO2) laser. II. Histopathological features. AB - A low-output CO2 laser was applied for microvascular anastomosis. The healing process of the vessel wall was examined histopathologically using light and scanning electron microscopes, and compared with that following conventional suture anastomosis. A power level of 21-40 mW and an exposure time of 5-15 sec were used. Under these conditions the laser beam reached the adventitia and media but not the intima. This made it possible to perform microvascular anastomosis without causing damage to the intima. Inflammatory reactions in the vessel wall were milder and endothelialization of the lumen surface occurred somewhat earlier with the laser technique than with the conventional technique of manual suture anastomosis. PMID- 3095470 TI - [Histological investigation on the penetration into the maxillary sinus of apatite implant]. PMID- 3095471 TI - Chromium 51-ethylenediaminetetraacetate test: a useful test in the assessment of inflammatory bowel disease. AB - We evaluated the usefulness of urinary excretion values in assessing mucosal damage in inflammatory bowel disease after administration of chromium 51-labeled EDTA either orally or rectally. In the oral study, 19 controls, 18 patients with Crohn's disease, and 13 patients with ulcerative colitis were given 100 microCi 51Cr-EDTA by mouth. The amount of 51Cr-EDTA in a 24-hour urine collection was expressed as a percentage of the ingested dose. The patients with Crohn's disease of the small bowel excreted 6.3% +/- 4.3%, which was significantly (P less than 0.001) higher than the percentage in patients with ulcerative colitis (1.7% +/- 1.1%) and controls (1.4% +/- 0.6%). In the enema study, 19 patients with ulcerative colitis, two with Crohn's disease, two with radiation colitis, and four controls (spastic colitis, lactose intolerance) were given 100 microCi 51Cr EDTA by retention enema. The patients with active colonic inflammation excreted 8.4% +/- 3.9% of the dose given by enema, which was significantly (P less than 0.01) higher than in other controls (1.9% +/- 0.91%) or patients with inactive colitis (2.2% +/- 1.9%). The 51Cr-EDTA excretion test is a safe, inexpensive test useful in evaluating patients with inflammatory bowel disease. It can be given orally to screen patients with abdominal complaints who are suspected of having Crohn's disease involving the small intestine, and when given by enema it provides additional objective assessment of idiopathic ulcerative colitis or proctitis. PMID- 3095472 TI - Bilirubin conjugate excretion and bilirubin uridine diphosphoglucuronyltransferase activity in nonjaundiced homozygous and heterozygous Gunn rats. AB - High-performance liquid chromatography was used to analyze the composition of bilirubin conjugates in bile from adult male and female outbred normal (JJ) and heterozygous (Jj) Gunn rats. Bile was examined directly without prior derivatization or extraction. Significantly higher bilirubin diglucuronide and lower bilirubin monoglucuronide (both C-8 and C-12 isomers) excretion in JJ rats was demonstrated. Bilirubin monoglucuronide C-8/C-12 ratios were similar in both genotypes, as was the percentage of bilirubin monoglucuronide monoglycoside diester. Hepatic bilirubin uridine diphosphoglucuronyltransferase activity showed a statistically significant positive correlation with the relative amount of bilirubin diglucuronide present in bile and a significant negative correlation with the amount of bilirubin monoglucuronide. The relative percentage of bilirubin monoglucuronide vs. diglucuronide in bile allows an indirect assessment of hepatic bilirubin uridine diphosphoglucuronyltransferase activity. PMID- 3095473 TI - Hyperoxic lung injury in mice: a possible protective role for prostacyclin. AB - Arachidonic acid metabolites have biologic properties that can mimic the pulmonary changes produced by hyperoxic exposure, but little information is available regarding their importance in this setting. The role of prostacyclin (PGI2) and thromboxane (Tx) A2 in oxygen-induced lung injury was evaluated by exposing mice to 100% oxygen for up to 4 days and measuring plasma and bronchoalveolar lavage (BAL) fluid concentrations of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a metabolite of PGI2, and TxB2, a metabolite of TxA2. To determine whether a relationship exists between changes in these arachidonic acid metabolites and the severity of the lung injury, we also measured mortality, BAL protein concentration, BAL angiotensin-converting enzyme (ACE) activity, and plasma lactate dehydrogenase activity, and we examined lung sections by light and electron microscopy. After 3 days of exposure to 100% oxygen, microscopic and biochemical changes consistent with mild lung damage were found, but there was no increase in either plasma or BAL 6-keto-PGF1 alpha concentration. On day 4, severe lung damage was present. and BAL 6-keto-PGF 1 alpha level increased threefold (P less than 0.001). The level of TxB2 in BAL fluid did not change on any day. Twice-daily administration of either a high (5 mg/kg) or a low (1 mg/kg) dose of indomethacin reduced BAL concentrations of 6-keto-PGF1 alpha, and it resulted in increased mortality and higher BAL protein concentration and BAL ACE activity. These data suggest that TxA2 has little if any role in the pathogenesis of oxygen-induced lung injury, whereas prostacyclin may play a protective role. PMID- 3095475 TI - The immunoregulatory nature of iron. II. Lymphocyte surface marker expression. AB - Previously, we presented preliminary evidence that supported our hypothesis for the immunoregulatory nature of iron [7]. The objective of the present work was to test that hypothesis in greater detail. Our approach was to examine the effect that iron had on the expression of the surface markers on lymphocytes that had been activated by pokeweed mitogen (PWM). The two categories of lymphoid surface molecules were enumerated on those cells; first were those that identify T lymphocytes and second, those that appear on the membrane of T cells following activation. The results, as regards T cell-associated molecules, demonstrated that iron suppresses the expression of the molecules identified by the monoclonal antibodies OKT3 and OKT4. It suppressed expression of the T4 molecule in PWM activated cells (30.6% +/- 4.5; n = 5) compared with untreated but activated cells (52.2% +/- 2.9; n = 5; P = 1.9 X 10(-3) resulting in a reduced helper:suppressor T cell ratio from 2.2 +/- 0.4 to 1.2 +/- 0.3. With regard to activation-associated lymphocyte markers, iron significantly enhanced expression of the receptor for transferrin as identified by the monoclonal antibody, OKT9. However, it failed to change significantly the expression of three other activation-associated markers, namely, Ia, T10, and the receptor that forms thermostable erythrocyte-rosettes (TE-R) with sheep red blood cells (SRC). We conclude from those results that iron has a differential immunoregulatory influence on the expression of certain lymphocyte surface molecules on actively dividing lymphocytes. PMID- 3095474 TI - Phorbol ester circumvents the need for macrophages as well as for mitogenic lectins in the stimulation of lymphocytes with wheat germ agglutinin or the calcium ionophores A23187 or ionomycin. AB - Numerous biochemical events precede the proliferation of primary lymphocytes stimulated by mitogenic lectins in the presence of macrophages. Various compounds can activate parts of this response. Specifically the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, (TPA), can replace the requirement for macrophages, apparently by mimicking the macrophage product interleukin 1 (IL1). Wheat germ agglutinin (WGA), itself a non-mitogenic lectin, is reported to cause a calcium flux, phosphatidylinositol turnover, and enhance interleukin 2 (IL2) synthesis. In spite of these positive responses, WGA inhibits DNA synthesis caused by mitogenic lectins. Nevertheless, in this study, we tested the possibility that together TPA and WGA could complement and bring about DNA synthesis. This prediction turned out to be true. The combination of two non mitogenic compounds resulted in lymphocyte proliferation. The TPA overcame the inhibitory effects of WGA. Moreover, macrophages were not required. The TPA also synergized with the calcium ionophores A23187 or ionomycin to cause lymphocyte proliferation in the absence of macrophages. WGA and the ionophores together did not cause proliferation, a finding which suggested that they fulfill the same roles. These observations led us to conclude that at least two signals were required for lymphocyte stimulation. One signal caused the mobilization of calcium and the other signal circumvented the need for macrophages or macrophage products possibly by mimicking diacylglycerol, the activator of protein kinase C. PMID- 3095476 TI - Characterization of 6 alpha-hydroxylation of taurochenodeoxycholic acid in pig liver. AB - The properties of the species-specific 6 alpha-hydroxylation of taurochenodeoxycholic acid were studied in subcellular fractions from pig liver. The hydroxylation was observed in microsomes but not in mitochondria. A partially purified cytochrome P-450 fraction in the presence of NADPH-cytochrome P-450 reductase, NADPH, and phospholipid catalyzed 6 alpha-hydroxylation of taurochenodeoxycholic acid at a 160-fold higher rate than the microsomes. This cytochrome P-450 fraction did not catalyze 6 alpha-hydroxylation of 5 beta cholestane-3 alpha,7 alpha-diol or testosterone, nor did it catalyze 7 alpha hydroxylation of cholesterol. PMID- 3095477 TI - Plasma metabolism of apolipoprotein A-IV in humans. AB - As assessed by molecular sieve chromatography and quantitation by a specific radioimmunoassay, apoA-IV is associated in plasma with the triglyceride-rich lipoproteins, to a high density lipoprotein (HDL) subfraction of smaller size than HDL3, and to the plasma lipoprotein-free fraction (LFF). In this study, the turnover of apoA-IV associated to the triglyceride-rich lipoproteins, HDL and LFF was investigated in vivo in normal volunteers. Human apoA-IV isolated from the thoracic duct lymph chylomicrons was radioiodinated and incubated with plasma withdrawn from normal volunteers after a fatty meal. Radioiodinated apoA-IV labeled triglyceride-rich lipoproteins, HDL, and LFF were then isolated by chromatography on an AcA 34 column. Shortly after the injection of the radioiodinated apoA-IV-labeled triglyceride-rich lipoproteins, most of the radioactivity could be recovered in the HDL and LFF column fractions. On the other hand, when radioiodinated apoA-IV-labeled HDL or LFF were injected, the radioactivity remained with the originally injected fractions at all times. The residence time in plasma of 125I-labeled apoA-IV, when injected in association with HDL or LFF, was 1.61 and 0.55 days, respectively. When 125I-labeled apoA-IV was injected as a free protein, the radioactivity distributed rapidly among the three plasma pools in proportion to their mass. The overall fractional catabolic rate of apoA-IV in plasma was measured in the three normal subjects and averaged 1.56 pools per day. The mean degradation rate of apoA-IV was 8.69 mg/kg X day. The results are consistent with the conclusions that: apoA-IV is present in human plasma in three distinct metabolic pools; apoA-IV associated with the triglyceride-rich lipoproteins is a precursor to the apoA-IV HDL and LFF pools; apoA-IV in LFF is not a free protein and its turnover rate is faster than that of apoA-IV in HDL; since no transfer of apoA-IV from the HDL or the LFF occurs, these pools may represent a terminal pathway for the catabolism of apoA-IV; and the catabolism of apoA-IV in HDL is dissociated from that of apoA-I although both apoproteins may reside on the same lipoprotein particles. PMID- 3095478 TI - Antagonistic effects of gamma interferon and steroids on tissue antigenicity. AB - A single injection of 10(5) U/kg of recombinant rat IFN-gamma increases the amount of tissue dendritic cells up to sixfold, and concomitantly induces the (capillary) endothelial cells to express class II MHC antigens. Both responses peak on the third day after IFN-gamma injection, and the antigen expression returns to basic levels on day 7. Simultaneous administration of 1 mg/kg/d of methylprednisolone entirely abolishes both responses. These observations demonstrate, for the first time, that IFN-gamma and steroids have antagonistic effects on class II MHC antigen presentation in tissue, and suggest that one immunosuppressive mechanism of glucocorticosteroids in organ transplantation is downregulation of graft antigenicity. PMID- 3095479 TI - Immunoglobulin G antibodies directed against protein III block killing of serum resistant Neisseria gonorrhoeae by immune serum. AB - Neisseria gonorrhoeae that resist complement-dependent killing by normal human serum (NHS) are sometimes killed by immune convalescent serum from patients recovering from disseminated gonococcal infection (DGI). In these studies, killing by immune serum was prevented or blocked by IgG isolated from NHS. Purified human IgG antibodies directed against gonococcal protein III, an antigenically conserved outer membrane protein, contained most of the blocking activity in IgG. Antibodies specific for gonococcal porin (protein I), the major outer membrane protein, displayed no blocking function. In separate experiments, immune convalescent DGI serum which did not exhibit bactericidal activity was restored to killing by selective depletion of protein III antibodies by immunoabsorption. These studies indicate that protein III antibodies in normal and immune human serum play a role in serum resistance of N. gonorrhoeae. PMID- 3095480 TI - Isolation and partial characterization of the reduction-modifiable protein of Neisseria gonorrhoeae. AB - We have isolated and purified the reduction-modifiable protein (protein III) from several strains of Neisseria gonorrhoeae. We have found them to be basic proteins (pI 8.6) and virtually identical. A similar but not identical protein was isolated from a meningococcal strain. Antibodies raised against this purified protein would absorb to whole bacteria, confirming that the protein is exposed on the surface of the organism. PMID- 3095481 TI - Effect of gamma interferon on cachectin expression by mononuclear phagocytes. Reversal of the lpsd (endotoxin resistance) phenotype. AB - IFN-gamma permits the endotoxin-induced production of cachectin by C3H/HeJ (endotoxin resistant) macrophages, apparently by facilitating endotoxin-induced cachectin biosynthesis at both transcriptional and posttranscriptional levels. IFN-gamma cannot induce cachectin biosynthesis by itself, nor does it markedly enhance cachectin production by endotoxin-induced peritoneal macrophages obtained from endotoxin-responsive mice. Elucidation of the precise mechanism through which IFN-gamma influences cachectin biosynthesis may permit a better understanding of the molecular events that follow endotoxin-induced activation of macrophages. Moreover, the permissive effect of IFN-gamma on cachectin biosynthesis might elicit enhanced endotoxin sensitivity in vivo. PMID- 3095482 TI - Human rheumatoid factor crossidiotypes. I. WA and BLA are heat-labile conformational antigens requiring both heavy and light chains. AB - Evidence was obtained that both the WA and BLA crossidiotype (XId) groups are conformational antigens requiring both L and H chains and that with heat denaturation the antigens that define the XIds and antigen-binding activity are lost in parallel. In contrast, the primary structure-dependent crossreactive idiotype (CRI), PSL2, which is only weakly detected on native Wa and Bla monoclonal rheumatoid factors (mRFs), became prominently detected on the heated Wa and Bla mRFs. Heat denaturation may provide a simple method for distinguishing Ids determined by conformational antigen from primary structure-dependent Ids. In addition to heat denaturation, some acid conditions commonly used for preparation of RFs were also found to cause marked loss of Id antigen. The finding of PSL2 CRI on Bla mRF indicates that this Id is not unique to the WA XId. PMID- 3095483 TI - HDL apolipoprotein A-I and HDL apolipoprotein A-II concentrations in male company employees in Westphalia aged 40 years and older. AB - The major structural components of high density lipoproteins were determined in the sera of 638 male employees aged 40 years and older. It was demonstrated that the HDL apolipoprotein A-I/HDL cholesterol ratio as well as the HDL apolipoprotein A-II/HDL cholesterol ratio are similarly correlated to a cumulative score of established risk factors for atherosclerosis. Most important, however, is the finding that the correlation of these ratios to the risk factor rating of atherosclerosis is found in subgroups with normal or elevated HDL cholesterol values. Furthermore, it is shown that the relative content of apolipoproteins A-I and A-II in individual HDL is partly dependent on the plasma concentration of HDL cholesterol and triglycerides. It is concluded that HDL composition may have an additional predictive significance for the development of atherosclerosis. PMID- 3095484 TI - Protein gradients in byssal threads of some marine bivalve molluscs. AB - Many marine bivalve molluscs produce byssal threads for attachment to solid substrata. Small (less than 10 mm) consecutive sections of the byssal threads of Mytilus edulis, M. californianus, Geukensia demissa, Atrina vexillum, and A. rigida were analyzed by amino acid analysis to determine if chemical composition remains constant as a function of location in thread segments. Nonlinear longitudinal protein gradients, probably involving collagen and an elastic protein, were found in the Mytilus species. In these, collagen peaks in the distal third of the thread. In Geukensia and the Atrina species, although the two differed greatly in composition, there is a clear nonvariability in composition of the thread within each species as a function of location in the thread. The adhesive plaque at the tip of the thread of all species examined differs substantially in composition from the remainder of the thread. Protein gradients in the threads of some bivalves may reflect specific adaptations evolved to respond to exposed habitats in high-energy environments. PMID- 3095485 TI - Matrix proteins of the teeth of the sea urchin Lytechinus variegatus. AB - The teeth of the sea urchin Lytechinus variegatus grow continuously. The mineral phase, a high magnesium calcite, grows into single crystals within numerous compartments bounded by an organic matrix deposited by the odontoblasts. Electron microscopic examination of glutaraldehyde-fixed Ethylene Diamine Tetra acetic acid (EDTA) demineralized teeth shows the compartment walls to be organized from multiple layers of cell membrane which might contain cytoplasmic protein inclusions. Proteins extracted during demineralization of unfixed teeth were examined by gel electrophoresis, high performance liquid chromatography, and amino acid analysis. The tooth proteins were acidic, they contained phosphoserine, and they were rich in aspartic acid. By contrast, the proteins of similarly extracted mineralized Aristotle's lantern skeletal elements were nonphosphorylated and were rich in glutamic acid. Vertebrate tooth and bone matrix proteins show similar differences. Surprisingly, an antibody to the principle rat incisor phosphoprotein showed a significant cross-reactivity with the urchin tooth protein, by dot-blot and enzyme-linked immunosorbent assay procedures. Thus, the urchin tooth proteins contain epitope regions similar to those which are phenotypic markers of vertebrate odontoblasts. Whether this is an expression of convergent or divergent evolutionary processes, it is likely that the matrix proteins play a similar role in matrix mineralization. The sea urchin tooth may thus be an excellent model for the study of odontoblast-mediated mineral-matrix relationships. PMID- 3095486 TI - Developmental analysis of lipids from wild-type and adipose60 mutants of Drosophila melanogaster. AB - A comparative developmental analysis was made of lipids from wild-type and adipose60 (adp60) mutants of Drosophila melanogaster. The lipid content and fatty acid profiles of late third instar larvae, pupae, and mature adults were characterized in methanol:chloroform extracts utilizing thin layer and gas-liquid chromatography. Total lipid content of mutant adults was approximately twice that of the wild-type, but no genotypic differences in lipid content were seen in earlier developmental stages. No sexual dimorphism was observed in total lipid content, although fatty acid profiles revealed some sexual differences. Many stage-specific differences in fatty acid profiles and lipid content were developmentally associated with each genotype. Mutants tended to retain the larval phenotype in lipid content and, to a lesser extent, in fatty acid profile. In comparison to wild-type, mutants tended to have increased lipid saturation, especially in 16-carbon fatty acids in mature adults and in 18:0 fatty acids in late larvae and pupae. No significant difference between the mutants and wild type appeared in the developmental profiles for 14:1 fatty acid isomers. Hence, adp60 does not alter the desaturation-elongation pathway, a secondary pathway for fatty acid desaturation in Drosophila, which received support from this analysis. PMID- 3095487 TI - Selectivity to K+ and Na+ of protoplast fractions isolated from different regions of Aspergillus nidulans hyphae. AB - The selectivity to K+ and Na+ of protoplast samples representing cytoplasm isolated from different regions of the hyphal filament of Aspergillus nidulans was investigated. Concentrations of both ions contained in successive protoplast fractions were measured. During lytic digestion, protoplasts were released first from apical regions and subsequently from progressively older regions of hyphae. A low K+/Na+ ratio was found in protoplasts containing primarily apical cytoplasm and a high K+/Na+ ratio was found in protoplasts originating from older regions of hyphae. The ratios were the same whether MgSO4 or mannitol was used as stabilizer. Absolute concentrations of both ions were higher in protoplasts of apical origin. Protoplasts stabilized in mannitol lost more ions than those stabilized in MgSO4 over an 8 h incubation period. Na+ losses were higher from apical protoplasts whereas K+ losses were higher from protoplasts liberated from older regions of hyphae. The addition of divalent metal cations (1.5 mM-Mn2+ or Mg2+) reduced losses of Na+ from protoplasts but did not affect loss of K+. Data obtained using protoplast samples were related to those obtained for intact mycelium. Absolute losses of both ions from mycelium were lower than for protoplasts but when compared on a protein basis the data suggested that protoplasts possess properties similar to those of intact mycelium in terms of K+ and Na+ selectivity. PMID- 3095488 TI - The effect of lowering the pH on the composition and metabolism of a community of nine oral bacteria grown in a chemostat. AB - Nine oral bacteria, associated with both healthy and diseased sites in the mouth, were grown at D = 0.05 h-1 (mean generation time 13.9 h) in a glucose-limited chemostat. After an initial period of steady-state growth at pH 7.0, pH control was discontinued. The pH then decreased until it stabilized at pH 4.1 after 9 d (16 generations), while the Eh rose from -165 mV to +160 mV. The lowering in pH resulted in the composition and metabolism of the flora being altered and in increased bacterial aggregation. At pH 7.0, 'Streptococcus mitior', Veillonella alcalescens and S. sanguis were most numerous while at pH 4.1 the counts of all bacteria fell except for Lactobacillus casei, which became predominant. The proportions of S. mutans within the community also increased while S. sanguis was recovered only occasionally and Bacteroides intermedius was not detected below pH 4.6. The survival at pH 4.1 of several other species would not have been predicted from earlier pure culture studies. Relative to pH 7.0, the community growing at pH 4.1 produced more lactic acid, washed cells had a greater glycolytic activity over a wider pH range but amino acid metabolism decreased. In general, when pH control was restored, so were the original patterns of metabolism and bacterial counts, except for B. intermedius, which was still not detected. The inverse relationship between S. sanguis and S. mutans, and the increase in proportions of L. casei and S. mutans during growth in a low pH environment parallel observations made in vivo and suggest that the chemostat can be used as a model for microbial behaviour in dental plaque. PMID- 3095489 TI - Identification and partial purification of a dipeptidyl aminopeptidase from Streptococcus faecalis. AB - A dipeptidyl aminopeptidase was identified in Streptococcus faecalis JH2SS and was partially purified (approximately 245-fold) by HPLC. Gel filtration chromatography indicated an Mr of 140 000. The partially purified enzyme exhibited a requirement for Co2+. The pH optimum for the hydrolysis of L-Val-L Ala-p-nitroanilide was approximately 9.5. The apparent Km for this substrate was 0.22 mM. The enzyme preferentially hydrolysed X-Ala-Y substrates, but also utilized X-Pro-Y substrates, and therefore is most closely related to the mammalian dipeptidyl aminopeptidase II (EC 3.4.14.-). The enzyme was inhibited by p-chloromercuribenzoate, but not by iodoacetate, N-ethylmaleimide or the serine protease inhibitor phenylmethylsulphonyl fluoride. PMID- 3095490 TI - Enhancement of Streptococcus faecalis infection and complement depletion in yeast treated mice. AB - Enhancement of Streptococcus faecalis infection and lowering of the complement level have been demonstrated in mice injected with a heat-treated suspension of baker's yeast (Saccharomyces cerevisiae). The leucocyte response to the infection was not affected. The yeast preparation showed, in vitro, an intense anti complementary activity on mouse serum and interfered with the microbial killing function of the mouse peritoneal macrophages. No significant stimulation of the growth of S. faecalis in vitro in the presence of the yeast was observed. The enhancement of the infection in mice treated with the yeast seems to be mediated, mainly, by complement depletion. PMID- 3095491 TI - Iron regulated outer membrane proteins of Escherichia coli: variations in expression due to the chelator used to restrict the availability of iron. AB - Iron restriction was induced in Escherichia coli O 111, E. coli O 164 and E. coli C by growing the organisms in trypticase soy broth containing ovotransferrin, desferal, EDDA (ethylenediamine-dihydroxyphenylacetic acid) or alpha,alpha' dipyridyl. There were marked qualitative and quantitative differences in the iron regulated outer membrane proteins expressed in the presence of the various iron chelators. Differences in the kinetics of growth were also noted. E. coli C was devoid of a ferric enterobactin iron uptake system. PMID- 3095492 TI - Lipopolysaccharide alteration is associated with induced resistance of Neisseria gonorrhoeae to killing by human serum. AB - On SDS-PAGE, solubilized and proteinase K treated preparations of Neisseria gonorrhoeae strain BS4 (agar) showed differences in silver stained lipopolysaccharide (LPS) patterns, before and after induction to resistance to serum killing by incubation for 3 h at 37 degrees C with low Mr fractions from lysates of guinea pig red blood cells. Preparations from the original serum susceptible gonococci and LPS purified from such bacteria showed two components, but the preparations from the serum resistant gonococci were deficient in the higher Mr component. Furthermore, on immunoblotting with fresh human serum (FHS), the two LPS components of the susceptible gonococci reacted strongly with IgM. With preparations from the serum resistant gonococci there was no reaction in the area corresponding to the higher Mr component and a weaker reaction with the component of low Mr. Purified LPS from the susceptible gonococci neutralized the bactericidal activity of FHS against N. gonorrhoeae strain BS4 (agar) probably by reacting with the relevant antibody, since heated FHS was no longer bactericidal when mixed with a source of complement (human placental serum) after prior reaction with the LPS. These neutralization tests coupled with the results of immunoblotting strongly suggest that increased serum resistance is due to the lack of the high Mr LPS moiety. PMID- 3095493 TI - Lithium treatment and cognitive changes in two mentally retarded patients. AB - Lithium carbonate was used to treat behavioral disorders in two mentally retarded patients. Although improvement was noted in the behaviors, cognitive performance, measured with the Peabody Picture Vocabulary Test, showed a decline, which was related to the serum lithium level. The implication of these changes is discussed. PMID- 3095494 TI - Comparison of a 52-kDa phosphoprotein from synaptic plasma membranes related to long-term potentiation and the major coated vesicle phosphoprotein. AB - In the in vitro hippocampal slice preparation a short tetanus induces long-term potentiation (LTP) and an increase in the post hoc phosphorylation of a 52-kDa protein in synaptosomal plasma membranes (SPM) prepared from these slices. This 52-kDa SPM phosphoprotein closely resembles the predominant phosphoprotein in coated vesicles, pp50, with respect to the insensitivity of its phosphorylation to Ca2+/calmodulin and cyclic AMP. This resemblance prompted us to compare in rat brain the 52-kDa SPM protein with pp50 in isolated coated vesicles. Both proteins appear to be very similar on basis of the following criteria: relative molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, peptide mapping, phospho-amino acid content, and isoelectric point. Since coated vesicles are thought to be involved in receptor-mediated endocytosis and membrane recycling, our data suggest that LTP-correlated changes in 52-kDa phosphorylation may reflect increased coated vesicle activity. PMID- 3095495 TI - Failure to maintain glycolysis in anoxic nerve terminals. AB - Synaptosomal glycolysis is stimulated eight- to 10-fold when the respiratory chain is inhibited by cyanide or by anoxia. However, the stimulation is transient and after 15 min declines toward the preanoxic rate. The decline is not seen when Ca2+ is absent or when the respiratory chain is inhibited by rotenone. The decline in glycolysis is reversible, is not due to substrate exhaustion, and is the cause, rather than the effect, of lowered synaptosomal ATP/ADP ratios. The failure to maintain glycolysis when the terminal oxidase of the respiratory chain is inhibited may have relevance to the sensitivity of the brain to anoxic damage. PMID- 3095496 TI - Incorporation of glycosylated beta-galactosidase into bovine brain synaptosomes. AB - Using a synthesized glycoprotein, beta-galactosidase modified with p-aminophenyl beta-D-galactopyranoside (beta-D-Gal beta-gal), the incorporation of the glycoprotein into bovine brain synaptosomes was studied. The uptake was mediated by a specific receptor to beta-D-galactoside, and was inhibited by GM1 ganglioside. The uptake was found to require energy and to be sensitive to metabolic inhibitors. Kinetic studies on beta-D-Gal beta-gal uptake indicated the presence of a saturable, carrier-mediated transport system in synaptosomes. By subcellular fractionation the beta-D-Gal beta-gal taken up was found in the fractions corresponding to the nucleus and membrane fragments, the soluble cytosomal fractions, and the mitochondria and lysosomes. The uptake was markedly increased by addition of Ca2+ to the incubation medium. The maximal uptake was obtained at pH 8.0 in the presence of 10 mM Ca2+ at 37 degrees C. By addition of a Ca2+ ionophore A23187, beta-D-Gal beta-gal uptake was increased in a dose dependent way parallel to the increase in the intrasynaptosomal concentration of Ca2+. Preincubation of synaptosomes with calmodulin antagonists such as trifluoperazine and N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide (W-7) was found to inhibit the uptake markedly, and diazepam, an inhibitor of Ca2+/calmodulin-dependent protein kinase, also inhibited the uptake. At a concentration between 1 and 10 microM, 50% inhibition of the uptake was observed with either inhibitor. On the other hand, the addition of dibutyryl cyclic AMP did not affect the uptake of the glycoprotein into synaptosomes. These results suggest that the incorporation of this macromolecule is dependent on a Ca2+/calmodulin-dependent protein kinase. PMID- 3095497 TI - The interactions between macrophages and developmental stages of Schistosoma mansoni: effect of macrophage function modulators on the viability of S. mansoni in vivo and in vitro. AB - ICR mice infected with Schistosoma mansoni developed sizable concomitant immunity to a challenge infection 10 weeks, but not 7 weeks, following the primary infection. At 7 weeks, postprimary-infection mice exhibited increased resistance to reinfection when treated with BCG or MDP. BCG even rendered noninfected mice resistant to infection. Macrophage function inhibitors such as silica and trypan blue did not abolish the concomitant immunity state, but they increased the worm burden due to a single infection, whether given before or after the infection. The onset of concomitant immunity in infected mice was paralleled by the appearance in their peritoneal exudate of schistosomulicidal-adherent macrophages. Such cells were evident at 9 but not 7 weeks of infection. The in vivo injection of MDP accelerated their appearance in infected mice, while silica, trypan blue, and carrageenan abolished it. The findings suggest that highly activated schistosomulicidal macrophages develop in infected mice, and might participate in the destruction of the invading parasite. PMID- 3095498 TI - Treatment of mice with macrophage colony stimulating factor (CSF-1) prevents the in vivo myelosuppression induced by murine alpha, beta, and gamma interferons. AB - Interferon (IFN) treatment has been shown to suppress the bone marrow in mice and humans, causing a leukopenia. In vitro studies with the mouse system have shown that colony stimulating factors (CSFs) antagonize the bone marrow suppressive, but not the antiviral or antiproliferative activities of IFNs. Partially purified murine macrophage colony stimulating factor (CSF-1) was evaluated for its ability to antagonize the myelosuppressive effect of murine (Mu) IFNs in vivo. All three interferon types (MuIFN-alpha, MuIFN-beta, and MuIFN-gamma) were used. IFNs and CSF-1 were administered subcutaneously for 3 successive days, blood was drawn by retro-ocular bleeding, and myelo-suppression was quantitated by subjecting the blood to total white blood cell (WBC) counts and to differential counts. The IFNs had similar effects, though MuIFN-gamma was a significantly more potent (50- to 100-fold) myelosuppressive agent than MuIFN-alpha or MuIFN-beta. Treatment with each of the three IFNs caused a reduction in the total WBC count (up to 40% reduction) and a generalized reduction of each of the three major leukocytes (lymphocytes, segmented polymorphonuclear leukocytes, and monocytes). Treatment with CSF-1 did not affect the total WBC count, but did cause a shift in the relative ratios of the leukocytes, decreasing the relative percentage of lymphocytes, and increasing the relative percentage of segmented polymorphonuclear leukocytes and monocytes. Combined treatment with CSF-1 and IFN inhibited the myelosuppressive activity of the IFNs, and restored the total WBC count to control levels. This restoration was largely due to increased levels of segmented polymorphonuclear leukocytes and monocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095499 TI - Adrenoleukodystrophy and beta-galactosidase deficiency: patient and carrier. AB - A patient with adrenoleukodystrophy and his mother, a carrier, showed an elevated ratio of very long-chain fatty acids to long-chain fatty acids and decreased beta galactosidase activity. Other lysosomal enzyme activities were normal except for the borderline level of arylsulfatase-A activity. However, the father and other patients with variant forms of adrenoleukodystrophy showed normal beta galactosidase and other lysosomal enzyme activities. PMID- 3095500 TI - Nitrates in the treatment of coronary artery disease. PMID- 3095501 TI - Long-term results of a cisplatin-containing combination chemotherapy regimen for the treatment of advanced ovarian carcinoma. AB - Sixty-two patients with advanced ovarian adenocarcinoma (stages III and IV) and without prior chemotherapy or radiotherapy were treated with a four-drug combination consisting of cyclophosphamide, hexamethylmelamine, 5-fluorouracil (5 FU), and cisplatin (Chex-UP). All patients were evaluable for toxicity and response, and survivors have been observed for a minimum of 48 months. The overall response rate to Chex-UP chemotherapy was 69%, with 12 patients (19%) achieving a pathologically confirmed complete remission (CR) as documented by a negative second-look laparotomy. Seven of the twelve patients (58%) who achieved a surgically confirmed CR were randomized to six cycles of intraperitoneal (IP) 5 FU. There have been seven relapses in patients who had a negative second-look laparotomy, but only four of the patients died from recurrent ovarian cancer. The median duration of remission following a negative second-look laparotomy was 53 months, while the median duration of survival has not been reached and will exceed 7.5 years. Seventeen patients (27%) achieved a clinical CR with chemotherapy but were found to have residual disease at second-look laparotomy. The median survival for these patients was 29 months, which was statistically inferior to that achieved for those patients with a negative second-look laparotomy (P less than .002), and only one patient is alive after 4 years. All patients who either achieved a partial response (PR) to therapy (14 of 62; 23%) or did not respond to therapy (19 of 62; 31%) died of ovarian cancer by 24 months. Thus, prolonged survival is associated with a surgically confirmed CR to induction therapy with Chex-UP. However, only a minority of advanced-stage ovarian cancer patients (15%) are alive 4 years after initiation of treatment with this regimen. PMID- 3095502 TI - Prognostic factors in metastatic carcinoma of unknown primary. AB - From January 1980 to June 1984, 70 patients with metastatic carcinoma of unknown primary treated with combination chemotherapy were analyzed for prognostic factors influencing objective response and survival. Suspicious germ-cell tumors and neuroendocrine tumors were excluded since patients with these malignancies tend to live longer than those with metastatic carcinoma of unknown primary. Objective response rate to combination chemotherapy was 28%. Median survival of all patients responding to combination chemotherapy was better than those not responding (16 v 3 months). In patients with good performance status, median survival was longer in responders than nonresponding patients (17 v 7 months). External lymph nodes or subcutaneous disease as the only site of disease and good performance status favorably influenced both objective response and survival, while the number of different metastatic sites favorably influenced only survival. Neutropenia and thrombocytopenia were appreciable but not fatal or a great cause of morbidity in those with good performance status. Thus, patients with metastatic carcinoma of unknown primary with good performance status or only external nodes or subcutaneous disease should be treated with combination chemotherapy regardless of age, histology, or number of different metastatic sites of disease. PMID- 3095503 TI - Sequential methotrexate, 5-fluorouracil, and cisplatin in the treatment of recurrent squamous-cell carcinoma of the head and neck: failure of hypertonic saline to reduce the nephrotoxicity of cisplatin. AB - Fifty patients with histologically proven squamous-cell carcinoma of the head and neck, recurrent after surgery and/or radiation therapy, were treated with a triple-drug combination of methotrexate (MTX), 250 mg/m2 intravenously (IV) on day 1, followed by 5-fluorouracil (5-FU), 600 mg/m2 IV on days 1 and 2, followed by cisplatin, 50 to 60 mg/m2 IV on days 3 and 4. Patients were randomly assigned to receive cisplatin either in 300 mL of 3% saline or with standard mannitol diuresis along with appropriate hydration. The courses of treatment were repeated every 3 to 4 weeks. Among 47 evaluable patients, there were four complete responses (CRs) and 17 partial responses (PRs) (9% and 36%, respectively). The median duration of response was 23 weeks and the overall survival was 7 months. The median survival of responders v nonresponders was 12 months and 6 months, respectively. Nausea and vomiting was experienced by all patients and diarrhea was experienced by 36% of patients. Neutropenia occurred in 37 patients (79%) and resulted in fever or infection in 11 patients (23%) and death in two patients. Mild renal failure (persistent serum creatinine greater than 1.5 mg/ dL) was observed in ten patients (21%), six treated with 3% saline and four treated with mannitol. The median cumulative dose of cisplatin that lead to the development of renal impairment was 485 mg/m2 in the hypertonic saline arm and 550 mg/m2 in the mannitol arm (P = .40). The antitumor activity of this regimen was not superior to that of sequential MTX and 5-FU. The use of hypertonic saline was not effective in reducing the renal toxicity of cisplatin. PMID- 3095504 TI - Phase I study of a combination of recombinant interferon-alpha and recombinant interferon-gamma in cancer patients. AB - Combinations of interferon-alpha and interferon-gamma demonstrate synergistic antiviral and anti-proliferative activity in vitro. Therefore, we initiated a clinical study of combination interferon therapy in humans. Eighteen patients with metastatic solid tumors received daily intramuscular (IM) injections of recombinant interferon-alpha-A (IFN alfa-2a, Roferon-A; Hoffman-LaRoche, Nutley, NJ) and recombinant IFN-gamma (rIFN-gamma) for 6 weeks. The dose levels were 0.5, 1.0, 2.0, and 5.0 X 10(6) U/m2/d of each interferon. A minimum of two patients were entered sequentially at each dose level. Fever, chills, fatigue, and a greater than or equal to 50% drop in granulocyte counts were observed at all doses. Severity of symptoms corresponded to increasing dose levels. In contrast to the tachyphylaxis to these symptoms that usually develops in patients treated with the individual interferons, many patients on this study experienced persistent fever and worsening fatigue over 6 weeks. The maximum tolerated dose was 1 X 10(6) U/m2/d of each interferon. One patient with renal-cell carcinoma achieved a partial remission (duration, 3 months). Enzyme-linked immunoassay analysis in all four patients for whom complete data were available revealed that peak blood levels of IFN alfa-2a on day 22 were about tenfold higher than on day 1. Because of the possibility of cumulative toxicity, the recommended starting dose for further studies is 0.5 X 10(6) U/m2/d of each interferon, with escalation to 1.0 X 10(6) U/m2/d after 1 month if tolerance is acceptable. Phase II investigations to explore the antitumor efficacy of this regimen are planned. PMID- 3095505 TI - Effect of difluoromethylornithine on the antiglioma therapeutic efficacy of intra arterial BCNU. AB - In an attempt to improve glioma management, an animal model was developed to evaluate the therapeutic efficacy of intra-arterial 1,3-bis(2-chloroethyl)-1 nitrosourea (BCNU). Furthermore, the model was used to study the antitumor activity of D,L-alpha-difluoromethylornithine (DFMO), a polyamine-biosynthesis inhibitor, used both as a single agent and in combination with intra-arterial BCNU. An N-methylnitrosourea-induced gliosarcoma (T9) was transplanted stereotaxically into the right caudate nucleus of male Fischer 344 rats. Animals receiving a single low-dose (5 mg/kg) intracarotid injection of BCNU 9 days following tumor implantation had a 57% increase in life span compared with untreated control rats (p less than 0.001). Intracarotid drug delivery was more effective than systemic (intraperitoneal) administration of the same dose of BCNU. When given as a single agent, DFMO demonstrated dose-dependent effectiveness. As part of a combined regimen, DFMO enhanced the antitumor therapeutic activity of both systemic (intraperitoneal) and intra-arterial BCNU. Survival times of animals receiving combined DFMO and intra-arterial BCNU were almost double those of untreated controls, and were significantly better than survival times of animals receiving combined DFMO and intraperitoneal BCNU. These findings suggest methods to optimize current clinical chemotherapy for glioma. PMID- 3095506 TI - Pathology of invasive pituitary tumors with special reference to functional classification. AB - Pituitary adenomas may remain intrasellar or infiltrate dura and bone. Invasive adenomas are not considered to be malignant; in biological behavior they are between non-infiltrative adenomas and pituitary carcinomas. The latter are defined as tumors with subarachnoid, brain, or systemic metastasis. Invasion may be defined radiologically, operatively, or histologically. On the basis of operatively assessed tumor size and gross invasion of dura and bone as well as immunocytochemical and ultrastructural analysis of 365 pituitary adenomas, the following data were obtained. There were 23 growth hormone (GH)-cell adenomas: 14% microadenomas and 86% macroadenomas; their overall frequency of invasion was 50%. There were 24 prolactin (PRL)-cell adenomas: 33% microadenomas and 67% macroadenomas, with an overall frequency of invasion of 52%. Mixed GH-cell and PRL-cell adenomas were found in 35 cases; 26% were microadenomas and 74% were macroadenomas, and the overall frequency of invasion was 31%. Sixty patients had adrenocorticotropic hormone (ACTH)-cell adenomas (Cushing's disease): 87% microadenomas and 13% macroadenomas; the overall frequency of invasion was 25% (in 8% of microadenomas and 62% of macroadenomas). Twenty patients had ACTH-cell adenomas (Nelson's syndrome): 30% microadenomas and 70% macroadenomas; the overall frequency of invasion in these cases was 50% (in 17% of microadenomas and 64% of macroadenomas). Silent ACTH-cell adenomas, 100% macroadenomas, were found in 11 patients, with an 82% frequency of invasion. There were 32 follicle stimulating and luteinizing hormone adenomas, all macroadenomas, with a frequency of invasion of 21%. Four patients had thyroid-stimulating hormone adenomas, all macroadenomas, with a 75% frequency of invasion. Null-cell adenomas were found in 93 cases: 2% microadenomas and 98% macroadenomas, with a frequency of invasion of 42%. There were 63 plurihormonal adenomas (GH, PRL, glycoprotein): 25% microadenomas and 75% macroadenomas, with a 50% overall frequency of invasion. Based on this study, and on their usual frequency of occurrence, the estimated rate of gross invasion by pituitary adenomas of all types is approximately 35%. It is concluded that immunocytochemical and ultrastructural characteristics of pituitary adenomas reflect the tendency of these tumors to infiltrate and hence may be of prognostic significance. PMID- 3095507 TI - Comparison of mannitol regimens in patients with severe head injury undergoing intracranial monitoring. AB - Eighty patients sustaining head injuries and presenting with Glasgow Coma Scale scores of 8 or less were entered into a prospective randomized study to assess the benefit of intracranial pressure (ICP) monitoring with two regimens of mannitol administration. Group I was treated with mannitol for ICP elevations greater than 25 mm Hg, while Group II received empirical mannitol therapy irrespective of ICP readings. No statistically significant differences in mortality rate or neurological outcome were demonstrated between the two groups. These results are comparable to those of several published series of head-injured patients receiving similar treatment from 1977 to 1982. However, those series must be reassessed in light of recently published studies with treatment initiated at lower levels of ICP. PMID- 3095508 TI - Aqueductal stenosis as isolated localization involving the central nervous system in children affected by von Recklinghausen disease. AB - The Authors report three cases of non tumoral aqueductal stenosis associated with von Recklinghausen disease in children. Moreover, 16 similar cases collected from the literature are illustrated. The clinical features are evaluated in light of literature's data. Among all 19 cases, the median age was 19 years (range 6-46 years) and 9 patients were under the age of 13 years. In this latter group, the most represented clinical symptoms were headache and gait disturbances. As regards the neuroradiological procedures, CT scan represented the best tool in the evaluation of the ventricular size. Our own three cases underwent to ventriculo-atrial shunt procedures, followed by clinical recovery (follow-up: 3 months-5 years). In conclusion it is felt that, among all the pathological events usually described in patients affected by neurofibromatosis, aqueductal stenosis seems to belong to the natural history of this disease. PMID- 3095509 TI - Indium-111 platelet kinetics in normal human subjects: tropolone versus oxine methods. AB - The effect of labeling media on the kinetics of[111In]platelets was evaluated by performing a paired crossover study in eight normal human subjects using tropolone and oxine methods. Platelets were labeled in autologous plasma with [111In]tropolone (In-tr) and in ACD-saline with [111In]oxine (In-ox) and reinjected. Starting at 1 hr, ten blood samples were obtained over an 8-day period. The in vivo platelet recovery was higher at 1 hr and throughout the 8 days of study with In-tr and the gamma camera images showed less uptake in liver and spleen than with In-ox. When platelet life-span (PLS) was estimated using all ten samples, only linear regression showed that the platelet life-span was longer with In-tr (10.7 +/- 1.5) than with In-ox (9.5 +/- 0.8). When the PLS was estimated excluding the 1-hr sample point, the life-span of platelets was significantly longer with In-tr than with In-ox based on three out of four models of curve fitting. These results demonstrate that platelets labeled with In-tr in plasma are preserved better in circulation and have equal or longer life-span than platelets labeled with In-ox in ACD-saline. PMID- 3095510 TI - Diagnostic value of free triiodothyronine in serum. AB - Serum free T3 concentration has been assessed in various thyroid conditions by a T3 analog method and the results compared with those obtained by equilibrium dialysis in the same individuals. The methodology is easy to perform and reproducible. FT3 determination appears to be especially valuable in detecting borderline thyrotoxicosis as in cases previously cured from thyrotoxicosis but suspected of relapse, or in nontoxic goitrous patients overtreated with T4. PMID- 3095511 TI - Indium-111 neutrophil imaging in ischemic colitis. PMID- 3095512 TI - Modulation of UDPglucuronosyltransferase activity in rats by dietary lipids. AB - Male Wistar rats were fed for 40 d a purified diet whose lipid source (60 g/kg diet) was coconut, peanut, corn or fish (herring) oil. A low lipid (lipid deficient) diet (corn oil, 2 g/kg diet) was also fed to some rats. There were no significant differences in final body weights of rats fed the coconut, peanut, and corn oil diets. Rats fed the fish oil diet gained less weight than those fed any other diet. However, liver weight, ratio of liver to body weight, and protein content were not affected by any of the diets. The plasma cholesterol concentration of rats fed fish oil was lower than that of the other groups of rats. This diet resulted in the highest cytochrome P-450 concentration and markedly enhanced epoxide hydrolase activity. No difference in the level in cytochrome P-450 was noted between the groups of rats fed the vegetable oils. Epoxide hydrolase activity was also significantly higher with the corn oil diet. Interestingly, only glucuronidation of group I substrates was stimulated by the fish or corn oil diets and lowered by the coconut oil diet. Liver microsomes of rats fed fish oil contained a high level of lipid peroxides; this diet greatly stimulated NADPH-dependent peroxidation. The differential stimulation of UDPglucuronosyltransferase activity towards group I substrates could be the results of a toxic action of the fish oil diet as suggested by the concomitant enhancements of epoxide hydrolase, transaminase activities and peroxide content. PMID- 3095513 TI - Biomonitoring of workers exposed to carcinogens: immunoassays to benzo(a)pyrene DNA adducts as a prototype. AB - A new tool for the study of occupational carcinogenesis is "molecular dosimetry" or biomonitoring to establish the biologically effective dose of carcinogens in workers. Human monitoring of biologically effective dose and preclinical response has the potential to flag the need for protective measures and/or surveillance. Comparable biologically effective dose and preclinical response data in humans and laboratory animals for whom tumor incidence is known can also enhance risk extrapolation between species. This paper will provide a brief overview of biomonitoring methods now under development, including advantages, limitations, applications to date, and research needs. Application to the monitoring of worker populations requires careful thought about the use to which monitoring data will be put. PMID- 3095515 TI - Parasitic infections in asymptomatic homosexual men: cost-effective screening. AB - The purpose of this study was to develop a cost-effective strategy for screening for enteric protozoan infections in homosexual men without gastrointestinal symptoms suggesting infection. One hundred and one homosexual men in Portland, Oregon, each submitted at least one unpurged stool sample; 91% submitted three samples each. Of these, 27% had Entamoeba histolytica, 61% had nonpathogenic protozoa with or without E. histolytica, 36% had a nonpathogen alone, and 3% had Giardia lamblia. Protozoan infection was highly associated with the practice of anilingus (p less than 0.005). Infection with E. histolytica correlated significantly with the presence of nonpathogenic protozoa (p less than 0.005). The following screening strategy was judged to be the most cost-effective: examine one sample first; if E. histolytica is found or if the sample is negative, no further investigation is required; if a nonpathogen is found, one additional sample should be obtained. This strategy had a sensitivity for E. histolytica of 85% and a cost of $136 per case detected. PMID- 3095514 TI - Quality of life of patients on long-term total parenteral nutrition at home. AB - Quality of life and quality-adjusted survival were measured for a cohort of 73 patients maintained on long-term parenteral nutrition at home (HPN) for periods ranging from six months to 12 years. Quality-adjusted survival was also modeled (although not directly observed) for this cohort under alternative therapeutic strategies (e.g., parenteral nutrition in hospital as needed). Using three utility assessment techniques (category scaling, time-tradeoff, direct questioning of objectives), quality of life was measured through interviews with 37 patients. The quality of life of the patients interviewed was good (mean value 0.73 where 0 represents death and 1.0 represents perfect health); for those who had experienced a period of chronic malnutrition before HPN, quality of life had improved. For the entire cohort, the estimate of quality-adjusted survival was four times greater with HPN than with the alternative therapeutic strategies (p less than 0.001). In comparison with alternative strategies, HPN significantly improves the quality of life of patients unable to sustain themselves with oral alimentation. Quality of life (utility) techniques can be used to evaluate the effectiveness of interventions for patients with chronic diseases. PMID- 3095516 TI - To test or not to test--to treat or not to treat: the decision-threshold approach to patient management. AB - The inability to consider explicitly factors that should enter into clinical judgment compromises physician efforts to make cost-effective decisions regarding diagnostic testing and treatment. The authors describe the decision-threshold approach, a decision-analysis strategy that helps physicians identify an optimal test-treatment decision based upon the prior probability of disease, the characteristics of the test (sensitivity, specificity, risk), and the benefits/costs of treatment. They also present a microcomputer graphics program that makes the decision-threshold approach readily available to physicians. PMID- 3095517 TI - Heterotopic ossification of the temporomandibular joint in a burn patient. PMID- 3095518 TI - Pathogenesis of apnea in preterm infants. PMID- 3095519 TI - Effect of prolonged clonidine administration on growth hormone concentrations and rate of linear growth in children with constitutional growth delay. AB - Sixteen prepubertal children with constitutional growth delay (10 boys and six girls, mean age 7.2 +/- 2.1 years) were administered a daily dose of clonidine (0.15 mg/m2) for a period of 1 year. Growth hormone levels, plasma somatomedin C, and linear growth rate were significantly increased at the end of the treatment. Six of the children maintained the higher growth rate even 6 months after treatment. These and other studies suggest that prolonged stimulation of the hypothalamus by clonidine may ameliorate the impairment of growth hormone release seen in some children with constitutional growth delay. Because of the low cost and the convenience of the oral route, administration of clonidine could be a mode of treatment in some children with poor growth. PMID- 3095520 TI - Nutritional rehabilitation in cystic fibrosis: controlled studies of effects on nutritional growth retardation, body protein turnover, and course of pulmonary disease. AB - The effects of a sustained increase in energy and protein intake on weight gain, growth, body protein metabolism, and the course of pulmonary disease were studied in 10 undernourished patients with cystic fibrosis unable to maintain nutrition and growth by the oral route and with declining nutritional and pulmonary status in the year prior to study. A 1-year course of nutrient supplementation using a semielemental high-nitrogen formula was delivered by nocturnal intragastric feeding or as an orally administered supplement; progress was compared with that of 14 height-, sex- and FEV1-matched patients with cystic fibrosis receiving conventional therapy. Supplementation resulted in a catch-up weight gain and sustained improvement in linear growth, with fewer pulmonary infections per year than during the initial observation period. Better weight gain and linear growth than in the comparison group were observed, as well as a significant reversal of the trend for deteriorating lung function. Compared with data from healthy children, 15N-glycine kinetics demonstrated increased protein breakdown and negligible net protein deposition in the treatment group prior to supplementation. After supplementation, synthesis in excess of breakdown, with net protein accretion, occurred by 1 month of supplementation. By 6 to 12 months a significant reduction in the previously high rate of mean synthesis and breakdown was observed, with maintenance of net anabolism. These dynamic changes in whole-body protein turnover reflect a long-term improvement in energy and protein intake, which can favorably affect nutrition, growth, and the course of pulmonary disease in problem cases of cystic fibrosis. PMID- 3095521 TI - Familial occurrence of protracted diarrhea of infancy. PMID- 3095523 TI - Effect of nonnutritive sucking on nutrient retention in preterm infants. PMID- 3095522 TI - Response to aluminum in parenteral nutrition during infancy. AB - The response to aluminum loading from parenteral nutrition (PN) solutions was determined in 20 infants with gestational ages 29 to 41 weeks and birth weights 880 to 3630 gm. Mean duration of PN was 43 days (range 5 to 175 days). Ten infants received a high Al load (from an experimental high calcium- and phosphorus-containing PN solution, with a measured Al content of 306 +/- 26 micrograms/L (mean +/- SE), n = 11), for up to 6 weeks. Ten infants received a lower Al load (from standard Ca-P solutions, measured Al content 144 +/- 16 micrograms/L, n = 11). Five infants received PN with a low Al load for longer than 6 weeks. The mean urine Al/creatinine (Cr) ratio (micrograms/mg) increased threefold, from 0.3 +/- 0.09 to 0.97 +/- 0.17 during PN in the entire group (P less than 0.001), and was significantly higher in infants who received greater Al loading (P less than 0.001). There was no significant difference between preterm and term infants in the rate of change in urine Al/Cr during the study. Urine Al was calculated to account for less than 50% of Al load. During the study, serum Al concentrations ranged from 6 to 318 micrograms/L (median 37 micrograms/L, compared with the median 18 micrograms/L for normal infants and children). Serum Al concentrations were not significantly changed during the study, or between infants in high or lower Al loading groups. Vertebrae from autopsy of two infants who received the lower Al containing PN for 71 and 152 days, respectively, stained positive for Al at the bone mineralization front. Thus, currently used PN solutions are contaminated with Al, urine Al concentration is higher with higher Al loading, and is not different in term and preterm infants. We suggest that renal elimination of Al in infants is incomplete, as assessed by lower urine Al excretion versus load, elevated serum Al concentration, and bone deposition of Al. PMID- 3095524 TI - Identification of children for whom routine monitoring of aminoglycoside serum concentrations is not cost effective. AB - On the basis of our clinical impression that aminoglycoside serum concentration measurements did not result in dosage changes in many children with normal renal function, data collected during pharmacokinetic consultations were evaluated to identify pediatric patients for whom routine serum concentration monitoring would not be cost effective. The frequency of peak or trough concentrations outside the desired ranges was related to age and duration of therapy in 88 children with normal renal function who were given recommended doses of gentamicin or tobramycin. Trough concentrations were outside the target range (greater than 2 micrograms/ml) in five of 26 patients who had received more than 10 days of therapy or were older than 18 years of age. In contrast, troughs were less than 2 micrograms/ml and did not significantly increase over the course of therapy in all patients who were younger than 18 years of age and had received less than 10 days of therapy. This latter group represented 36% of all aminoglycoside pharmacokinetic consultation requests to our service. In addition, when infusion technique and sample time were meticulously controlled, peak concentrations were greater than or equal to 4 micrograms/ml in all patients who had received a dose of approximately 2.5 mg/kg. We conclude that routine peak and trough measurements are unnecessary in patients between 3 months and 18 years of age unless duration of therapy extends beyond 10 days, renal function is impaired, there is a clinical need for higher doses or shorter dosing intervals, or a potential nephrotoxin has been administered in the previous 3 months. PMID- 3095525 TI - Factors involved in cycle development of a steam-in-place system. PMID- 3095526 TI - Pretreatment equipment guidelines for ion exchange demineralization systems. PMID- 3095527 TI - The effects of cooling rate on solid phase transitions and associated vial breakage occurring in frozen mannitol solutions. PMID- 3095528 TI - Nonisothermal methods for stability prediction. PMID- 3095529 TI - In line validation of sanitizing agents in aseptic processing areas. PMID- 3095530 TI - Partial splenectomy for benign cystic lesions of the spleen. AB - Cystic lesions of the spleen are uncommon, about 600 cases being reported in the world literature. This report concerns three pediatric patients treated by partial splenectomy for benign cyst. In the world literature most of the cystic lesions of the spleen are treated by splenectomy and more recently by partial splenectomy. The infected lesions are treated by splenectomy or by incision and drainage only. Partial splenectomy has evident advantage over splenectomy. Although in the world literature we have not found a single case of infected splenic benign cyst treated by partial splenectomy, we believe that this procedure also has an advantage over drainage as the infected and necrotic part of the cyst is removed, thereby reducing morbidity and further possible complications. PMID- 3095531 TI - Preoperative home elemental enteral nutrition in complicated Crohn's disease. AB - Home elemental nutrition (HEN) was used in 11 children and adolescents with complicated Crohn's disease to relieve their immediate symptoms and make them more fit for definitive surgery. HEN resulted in symptomatic relief, weight gain from a mean of 47 to 53 kg (P less than .001) and reduction in prednisone requirements from a mean daily dose of 30 to 6 mg (P less than .001). The seven patients who subsequently underwent definitive bowel resection suffered no surgical complications. HEN was well tolerated by all patients. HEN offers a simple, safe, and cost effective means of preparing patients with complicated Crohn's disease for operation. PMID- 3095532 TI - Thrombosis and infection complicating central venous catheterization in neonates. AB - To determine the risk of complication associated with Broviac central venous catheterization in neonates, we reviewed the records of 107 infants who were catheterized an average of 5 weeks after birth and cared for in our neonatal intensive care unit. Forty-five of the 107 neonates (42%) had one or more catheter-related complications. Infants with complications had significantly lower birth weights and gestational age, longer duration of catheterization, and more repeat catheterizations than infants without complications. The mortality rate in infants with complications was not different than that of infants without complications. The most common complications were thrombosis (23 neonates) and infection (20 neonates). The birth weight and the number of catheterizations were the best predictors of the risk of complications as determined by multiple regression analysis. We conclude that the risk of complication associated with central venous catheterization is high in our population of predominantly premature neonates; that the risk of complication is increased in neonates weighing less than 1,000 g or requiring more than one catheter; and that despite the high complication rate central venous catheterization was not associated with increased mortality in this population. PMID- 3095533 TI - Comparison between the iontophoretic and passive transport of thyrotropin releasing hormone across excised nude mouse skin. AB - Thyrotropin releasing hormone [L-proglutamyl-L-histidyl-L-proline amide (TRH)], a tripeptide with molecular weight of 362 and a pKa of 6.2, was used as a model peptide for in vitro passive and iontophoretic diffusion cell studies using excised dorsal nude mouse skin. The results indicate that both the charged and uncharged TRH fluxes across the excised tissue were greater than those obtained by passive diffusion alone. The steady-state flux of both the uncharged and charged TRH was directly proportional to the applied current density, with flux being greater for the uncharged TRH. Additional studies on the transport of methylene blue indicate that transport may be occurring through pores, and that positive ions are preferentially passed through the skin. These results imply that the steady-state flux of TRH is primarily due to a direct, electrically induced ion motion and convection. A practical implication of these results is that it may be possible to enhance and control the transdermal delivery of peptides. PMID- 3095534 TI - Rehabilitation exercises following inversion ankle sprains. PMID- 3095535 TI - Integrity of polydioxanone sutures: a case report. AB - Certain conditions have been found to hasten the breakdown of absorbable PDS (polydioxanone) sutures. It is important that surgeons handle the sutures carefully to avoid premature breakdown. PMID- 3095536 TI - A characterization of the antinociception produced by intracerebroventricular injection of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate in mice. AB - There is evidence that 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) acts as an intracellular Ca++ antagonist producing decreases in free intracellular Ca++ and inhibiting many cellular processes dependent upon intracellular Ca++. Intracerebroventricularly administered TMB-8 was active in the mouse tail-flick test (ED50 = 50 micrograms), and this antinociceptive response was antagonized by naloxone (AD50 = 0.28 mg/kg s.c.), Ca++ (0.2-0.4 mumol i.c.v.) and, to a lesser degree, by ethylene glycol bis (beta-aminoethyl ether)N,N1-tetraacetic acid (0.02 and 0.06 mumol i.c.v.). TMB-8 (i.c.v.) was only marginally active in the p-phenylquinone test. The potency of TMB-8 (i.c.v.) was potentiated 10-fold in morphine-tolerant mice in the tail-flick test (ED50 = 2.5 micrograms). TMB-8 inhibited contraction of stimulated ilea (IC50 = 2.2 microM), an effect which was neither antagonized nor reversed by naloxone (1 microM). TMB 8 did not potentiate morphine, or was it potentiated by morphine, in the stimulated guinea pig ileum. Procaine, but not lidocaine showed dose-dependent activity in the tail-flick and p-phenylquinone tests (ED50 values, 136 and 83 micrograms, respectively, i.c.v.). The antinociception produced by procaine (i.c.v.) in the tail-flick test was antagonized by naloxone (AD50 = 0.4 mg/kg s.c.) Lidocaine (100 micrograms i.c.v.) produced only 30% maximum possible effect in the tail-flick tests, and was inactive in p-phenylquinone tests. Doses of lidocaine greater than 100 micrograms i.c.v. resulted in lethality of greater than 50% of the animals tested. Thus, the activity of TMB-8 resembles that of opiates in that both are antagonized by Ca++ or naloxone in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095537 TI - Gastric antisecretory and antiulcer properties of enprostil, (+/-)-11 alpha, 15 alpha-dihydroxy-16-phenoxy-17,18,19,20-tetranor-9-oxoprosta- 4,5,13(t)-trienoic acid methyl ester. AB - Prostaglandins of the E series have been shown, both in animals and humans to produce gastrointestinal antisecretory and antiulcer effects. Enprostil, a modified allenic prostaglandin E was found to be a highly potent inhibitor of gastric HCl secretion in a variety of species. In rats, in which both the pylorus and esophagus were ligated, p.o. ED50 values and 95% CL for inhibiting acid secretion evoked by histamine, pentagastrin and carbachol were 9.9 (6.7-15), 40 (11-145) and 0.83 (0.78-0.89) micrograms/kg, respectively. In inhibiting histamine-evoked acid secretion, enprostil was more potent when administered p.o. than when injected into the duodenum or s.c. When enprostil was injected directly into the pouch of Heidenhein dogs, intense antisecretory activity occurred, ED50 = 0.9 (0.7-1.1) micrograms/kg, whereas, when given p.o. to the main stomach the ED50 was 6.6 (3.2-13.6) micrograms/kg. Administration of cimetidine either p.o. or to the pouch resulted in virtually identical ED50 values, viz., 2.9 and 3.1 mg/kg. Enprostil also inhibited dimaprit- and pentagastrin-induced acid secretion in cats with permanent gastric fistulae. The oral ED50 values for inhibiting acid secretion evoked by these two secretagogues were 2.5 (1.4-4.3) and 0.8 (0.5-1.5) micrograms/kg, respectively. Enprostil was extremely potent in preventing indomethacin plus "cold stress" ulcers in rats. When given orally the ED50 was 0.61 (0.31-1.22) and s.c. it was 22 (9.0-52) micrograms/kg. It was also highly potent in preventing cysteamine-induced duodenal ulcers when given p.o., ED50 = 20 (17-23) micrograms/kg. Thus, enprostil is a highly potent antisecretory and antiulcer agent. It appears to act topically; directly at gastric mucosal sites. PMID- 3095538 TI - Analysis of airway responses to A23187 in the cat. AB - Airway responses to ionophore A23187 were investigated in anesthetized, paralyzed cats under conditions of controlled ventilation. Intravenous injections of A23187 caused dose-related increases in transpulmonary pressure and lung resistance and dose-related decreases in dynamic compliance and aortic pressure. Airway responses to A23187 were reduced by sodium meclofenamate, a cyclooxygenase inhibitor, in a dose that decreased bronchomotor responses to the prostaglandin precursor, arachidonic acid. The cyclooxygenase inhibitor had no significant effect on airway responses to U-46619, a prostaglandin endoperoxide analog whose actions mimic those of thromboxane A2. Bronchomotor responses to ionophore A23187 were also reduced by SQ 29,548, a thromboxane receptor antagonist. SQ 29,548 reduced airway responses to the thromboxane A2 mimic, U-46619, but had no significant effect on airway responses to prostaglandins D2 or F2 alpha. These data indicate that ionophore A23187 constricts smooth muscle in central airways and in peripheral portions of the lung. In addition, these results suggest that in the closed-chest cat, bronchoconstrictor responses to A23187 are mediated mainly by formation of cyclooxygenase products and that a substantial part of the response is due to thromboxane A2 formation. PMID- 3095539 TI - Actions of nizatidine on the rat uterus, dog stomach and experimentally induced gastric lesions. AB - Nizatidine is a potent and selective antagonist of histamine. The histamine induced relaxation of the KCl-treated rat uterus was inhibited dose-dependently by nizatidine. The inhibition was characterized by displacement of the dose response to histamine to the right, in parallel, without depression of the maximum. The affinity of nizatidine for the histamine H2-receptor of the rat uterus was about 10 times that of cimetidine. The steady-state dose-response acid outputs stimulated by histamine from the Heidenhain pouch and the gastric fistula were also shifted dose-dependently by nizatidine, in parallel, to the right. The inhibition was consistent with a surmountable antagonism of histamine. At high (10(-4) to 10(-3) M) concentrations, nizatidine increased the motility of the guinea pig stomach and duodenum in vitro; this effect was abolished noncompetitively by atropine (10(-8) M) and pyrilamine (10(-4) M). Both nizatidine and cimetidine administered s.c. showed "cytoprotective" action by reducing the gastric lesions induced by 1) aminoguinidine and pylorus ligation and 2) HCl plus aspirin in the rat. On a weight and molar basis, nizatidine was 4 and 5.25 times as effective as cimetidine, respectively. This cytoprotective action of nizatidine was found when acidity and total acid load in the stomach were not affected by the histamine H2-receptor antagonist. PMID- 3095540 TI - Evaluation of two anticonvulsant amino-pyridazine derivatives in the conflict test in rats. AB - Two amino-phenyl-pyridazine derivatives, SR 41378 and CM 40907, have been reported to antagonize seizures in mice, rats and Papio papio baboons with comparable potencies. Structurally, SR 41378 differs from CM 40907 by an additional chlorine in position 6 of the phenyl ring. In the present study the activity of these two compounds in the operant approach-avoidance conflict test in rats was examined and compared with that of diazepam, pentobarbital, meprobamate and valproate. SR 41378 increased punished responding, a measure of anticonflict activity (ED50 = 5.2 mg/kg), and decreased nonpunished responding, a measure of sedative activity, with a threshold active dose of 20 mg/kg i.p. The overall potency of SR 41378 was comparable to that of pentobarbital. CM 40907 (10 40 mg/kg i.p.) did not affect punished responding and decreased nonpunished responding at the dose of 40 mg/kg i.p. The duration of the anticonflict activity of SR 41378 increased with the dose and lasted over 4 h at the 20-mg/kg i.p. dose. At this dose, sedation lasted 1 h. An increase in anticonflict potency and tolerance to sedation were observed after a 5-day treatment with SR 41378 (20 mg/kg i.p.). The anticonflict and sedative activities of SR 41378 were not antagonized by Ro 15-1788 or CGS 8216. In vitro SR 41378 did not interact with benzodiazepine receptor sites. In conclusion, although CM 40907 and SR 41378 exhibit similar anticonvulsant activities, the present study reveals a major pharmacological difference between the two compounds because SR 41378 also possesses anticonflict properties. PMID- 3095542 TI - Abdominal wound closure with polydioxanone (PDS). PMID- 3095541 TI - Effects of anticonvulsant drugs on substantia nigra pars reticulata neurons. AB - Enhancement of gamma-aminobutyric acid transmission within the substantia nigra has been shown to prevent the motor manifestations of chemically induced and kindled seizures. These findings raise the possibility that the substantia nigra might constitute a site of anticonvulsant drug action if these drugs share an ability to suppress propagation of seizure activity from the nigra to motor effector sites. The current studies monitored effects of a diverse group of anticonvulsant drugs on the extracellular, single unit activity of nondopaminergic neurons of the substantia nigra pars reticulata in awake, paralyzed and locally anesthetized male rats. Intravenous phenytoin (1.25-160 mg/kg) and carbamazepine (1.25-40 mg/kg) did not alter neuronal firing at any dose. Conversely, both diazepam (31.25-8,000 micrograms/kg) and clonazepam (2-500 micrograms/kg) partially inhibited firing (to 46 +/- 11% and 59 +/- 6% of base line rates, respectively), although clonazepam was approximately 16 times more potent in eliciting equivalent degrees of inhibition. Valproic acid (5-640 mg/kg) and phenobarbital (1.25-80 mg/kg) also slowed firing to 65 to 70% of base-line rates, but did so only at the highest doses administered. However, the anesthetic barbiturate pentobarbital (0.3125-80 mg/kg) completely suppressed firing by the highest dose tested. Of those drugs used exclusively for treatment of absence seizures, trimethadione (12.5-800 mg/kg) caused dose-related inhibitions to 37.6 +/- 9.8% of base-line, whereas ethosuximide (12.5-800 mg/kg) markedly stimulated firing, nearly doubling firing rates after the 200 mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095543 TI - A four-year experience with needle catheter jejunostomy. PMID- 3095545 TI - CO2 uterine distention for hysteroscopic septal incision. PMID- 3095544 TI - Necrotising fasciitis secondary to a strangulated femoral hernia containing a perforated sigmoid diverticulum. PMID- 3095546 TI - Association of embolic stroke in pregnancy with the lupus anticoagulant. A case report. AB - Recently the association of recurrent spontaneous abortions and intrauterine fetal death was linked to the lupus anticoagulant (LA). LA is an immunoglobulin directed against phospholipid, causing characteristic changes in coagulation tests, and is associated with an increased risk of thrombosis. We treated a pregnant woman who presented with an embolic stroke and laboratory evidence of LA. PMID- 3095547 TI - Effects of oral contraceptives on carbohydrate metabolism. AB - Both estrogens and progestogens modify carbohydrate metabolism, and their ultimate effect depends upon the ratio of one to the other. The effect of progestogens themselves, which are responsible for increased insulin secretion and for insulin resistance, varies according to their androgenicity but increases according to the series pregnane, estrane and gonane. In contrast, estrogens impair the initial secretion of insulin by the pancreas. The prolonged use of combined oral contraceptives containing the powerful progestogen levonorgestrel is associated with mild but continuing glucose intolerance and with marked insulin resistance. PMID- 3095548 TI - Increased intrathecal immunoglobulin synthesis of both kappa and lambda types in patients with systemic lupus erythematosus and central nervous system involvement. AB - The concentration of immunoglobulins in paired serum and cerebrospinal fluid (CSF) specimens from 15 patients with systemic lupus erythematosus (SLE) and central nervous system (CNS) involvement (CNS-SLE) were determined based on their light chain properties. Eight patients with SLE without CNS involvement and 20 patients with noninflammatory neurological diseases were also studied for comparison. We found that both of the CSF Ig-k (immunoglobulin kappa) and Ig-1 (immunoglobulin lambda) indices were significantly elevated, indicating the increased intrathecal immunoglobulin synthesis of both kappa and lambda types in patients with CNS-SLE. Moreover, the CSF Ig-k and Ig-1 indices correlated well with each other, and both indices were found to decrease remarkably when the CNS manifestations subsided after successful treatment. In 4 of 15 patients, intrathecal synthesis of free light chains in addition to Ig bound light chains seemed to be increased. These observations provide substantial evidence for polyclonal B lymphocyte activation within the CNS. PMID- 3095549 TI - Pulmonary complications of total parenteral nutrition in a neonate. PMID- 3095550 TI - Effect of carbon dioxide on the growth and form of Candida albicans. AB - The effect of CO2 on the growth of 31 strains of Candida albicans was studied in serum and in a defined medium containing urea, ammonium chloride, asparagine, glutamine or acetamide as the nitrogen source. CO2 10% enhanced the mycelial growth of all strains when the medium contained an appropriate constituent to mediate its effects. The effect of CO2 was most clearly demonstrated at 30 degrees C when it induced a characteristic growth form consisting of a single swollen blastospore giving rise to a long, unbranched mycelial tube with few secondary blastospores; in atmospheric concentrations of CO2 only blastospore growth occurred. Growth in the blastospore form was more rapid in CO2 10% than in air. Bicarbonate ions had no effect on mycelium formation. The result suggest that the induction of germ-tubes and mycelial growth is essentially a physical phenomenon caused by the intracellular accumulation of CO2 in limited nutrient conditions, a view consistent with other reported laboratory and clinical findings. PMID- 3095551 TI - Dissociation of surface properties and "intrinsic" resistance to beta lactams in Pseudomonas aeruginosa. AB - Carbenicillin resistance in strains of Pseudomonas aeruginosa isolated in Britain is mediated more frequently by "intrinsic factors" than by beta-lactamase production. Intrinsically carbenicillin-resistant isolates almost invariably were more resistant to azlocillin, cefoperazone, cefotaxime, ceftazidime, chloramphenicol, tetracycline and nalidixic acid than were carbenicillin susceptible strains. This cross-resistance to different classes of antimicrobials suggested an impermeability-based mechanism of resistance, perhaps involving the outer membrane. The structure and composition of the outer membrane of the pseudomonas cell also influences the O-serotype specificity and the susceptibility to many bacteriophages. We therefore examined these properties for possible relationships to antibiotic resistance. Carbenicillin-resistant (122) and -sensitive (127) P. aeruginosa strains from 24 hospitals were compared. Serotype O:1, O:3, O:6, O:10 and O:11 strains predominated in both groups. Non typable and polyagglutinating strains were infrequent in both groups. With one possible exception, none of 18 bacteriophages showed a significant preference for carbenicillin-resistant or -sensitive strains. Variation between strains was observed in the electrophoretic profile of LPS and this could be related in part to serotype, but not to antibiotic resistance. Our results contrast with those of earlier small-scale studies which have claimed relationships between surface properties and antibiogram in P. aeruginosa, and suggest that interpretation of the minor changes in LPS sometimes observed in association with the development of antibiotic resistance in vitro requires caution. PMID- 3095552 TI - Sensitized chick cells in the indirect haemagglutination test for echinococcosis. AB - An indirect haemagglutination (IHA) test was performed with chick red blood cells (RBC) on sera from 26 confirmed cases of echinococcosis and 45 control sera. The results were compared with those obtained in an IHA test with sheep RBC on the same batches of sera; both tests were equally sensitive. The chick cells settled quickly and the results could be determined within 30-45 min. Heterophilic antigen was not a problem. This study also showed that chick cells stabilised by the double-aldehyde method, could be sensitised with the antigen and then stored at 4 degrees C for up to 31 days before use in the IHA test without loss of sensitivity. The use of sensitised double-aldehyde stabilised (DAS) chick cells in IHA tests provides a rapid diagnostic test in echinococcosis. PMID- 3095553 TI - Enhancement of sensitivity of the haemagglutination test for echinococcosis by use of Staphylococcus aureus protein A. AB - A modification of the indirect haemagglutination test is described for the serodiagnosis of echinococcosis. In the modified test the Cowan I strain of Staphylococcus aureus, which contains protein A, was used to enhance haemagglutination of sensitised red cells. The test was performed in parallel with the indirect haemagglutination test on 31 sera from surgically-confirmed cases of hydatid disease and on 45 sera from healthy blood donors. Use of S. aureus protein A enhanced the sensitivity of the test and greatly increased the titres obtained with most of the sera. None of the sera from healthy blood donors exhibited a titre greater than 64, whereas all but two of the sera from cases of hydatid disease exhibited titres greater than 128. The immunoassay is simple, inexpensive and requires little technical skill. It has the potential for wide application in the serodiagnosis of echinococcosis. PMID- 3095554 TI - Use of freshly prepared rat hepatocytes to study toxicity of blooms of the blue green algae Microcystis aeruginosa and Oscillatoria agardhii. AB - Extracts from blue-green algal blooms (Microcystis aeruginosa and Oscillatoria agardhii) from different lakes in southeastern Norway were tested for toxicity toward freshly prepared rat hepatocytes. The toxicity effects were scored by means of morphological studies of the cells and by measuring leakage of the enzyme lactate dehydrogenase (LDH) from the cells. The results with the hepatocytes correspond well with results from the traditional mouse bioassay, concerning both ability to distinguish between toxic and nontoxic samples and estimation of relative toxicity. Morphological changes due to toxic effects on the plasma membrane appeared earlier than leakage of enzyme from damaged cells. The results indicate that the hepatocyte-toxicity assay system might be well suited for screening purposes concerning water contamination by blue-green algae. PMID- 3095555 TI - Association between PCBs and lower embryonic weight in black-crowned night herons in San Francisco Bay. AB - Reproductive problems, including congenital malformations, reduced hatching success, and decreased survival of hatchlings, have been observed in colonial nesting water birds at the San Francisco Bay National Wildlife Refuge (SFBNWR). Twenty-four black-crowned night heron (Nycticorax nycticorax) eggs were collected from SFBNWR in 1983. Twelve of these were collected from separate nests when late stage embryos were pipping, and an additional egg was randomly collected from each nest for organochlorine analysis. Overt anomalies and skeletal defects were not apparent. Embryonic weights (with partially absorbed yolk sacs removed) were 15% lower (p less than 0.05) in SFBNWR embryos compared to control embryos from the Patuxent Wildlife Research Center (PWRC). Crown-rump length and femur length were shorter for SFBNWR embryos. The geometric mean polychlorinated biphenyl (PCB) concentration in SFBNWR eggs was 4.1 ppm wet weight, with a range of 0.8 52.0 ppm. A negative correlation (r = -0.61; p less than 0.05) existed between embryonic weight and log-transformed PCB residues in whole eggs collected from the same nest at SFBNWR, suggesting a possible impact of PCBs on embryonic growth. A correlation with embryonic weight did not occur for DDE [1,1-dichloro 2,2-bis(p-chlorophenyl) ethylene] residues. Liver microsomal aryl hydrocarbon hydroxylase activity was neither significantly elevated nor correlated with PCB, DDE, or PCB plus DDE log-transformed residues. It is unknown whether the apparent association between PCBs and lower weight is persistent through hatching. PMID- 3095556 TI - Age-related dose response of selected reproductive parameters to acute cadmium chloride exposure in the male Long-Evans rat. AB - Groups of male Long-Evans rats 30, 50, or 70 d old were injected subcutaneously (sc) with a single dose of 0, 5.5, 11.5, or 24.6 mumol Cd/kg as cadmium chloride. All animals were killed 60 d after treatment. At 2 h prior to sacrifice, the rats were injected sc with 100 IU human chorionic gonadotrophin (hCG) to maximally stimulate serum testosterone concentrations. After sacrifice the testes, epididymides and seminal vesicles were removed and weighed. Cardiac blood was taken, and serum concentrations of testosterone (sT) and follicle-stimulating hormone (sFSH) were determined. Sperm concentration in luminal fluid collected from the vas deferens was determined. Significant (p less than 0.01) dose dependent effects for all measured reproductive parameters were noted in the 70-d old animals, while no effects were seen in the 30- or 50-d-old rats in either seminal vesicles weight or hCG-stimulated sT concentration. In the absence of significant (p greater than 0.05) changes in body weight gain, effects were seen in testes and epididymides weight, sperm concentration, and sFSH in the 70-d-old rats at Cd doses that were lower than those necessary to bring about similar changes in the 30- or 50-d-old animals. The sensitive indicators of Cd exposure in all age groups were testicular weight greater than epididymal weight greater than vas deferens sperm concentration greater than sFSH concentration. Seminal vesicle weight and sT concentration were found to be the least sensitive. Regression analyses indicated a significant interaction of age with dose; the 70 d-old rats required 30-61% less Cd/kg to cause a 50% change in a measured parameter than did the 30-d-old animals, while the 50-d-old rats required 15-47% less. PMID- 3095557 TI - Benefits of immediate jejunostomy feeding after major abdominal trauma--a prospective, randomized study. AB - Benefits of immediate postinjury nutritional support remain ill defined. Seventy five consecutive patients undergoing emergent celiotomy with an abdominal trauma index (A.T.I.) greater than 15 were randomized prospectively to a control group (no supplemental nutrition during first 5 days) or enteral-fed group. The enteral patients had a needle catheter jejunostomy (N.C.J.) placed at laparotomy with the constant infusion of an elemental diet (Vivonex HN) begun at 18 hours and advanced to 3,000 ml/day (3,000 kcal, 20 gm N2) within 72 hours. Control and enteral-fed groups were comparable with respect to demographic features, trauma mechanism, shock, colon injury, splenectomy, A.T.I., and initial nutritional assessment. Twenty (63%) of the enteral patients were maintained on the elemental diet greater than 5 days; four (12%) needed total parenteral nutrition (T.P.N.). Nine (29%) of the control patients required T.P.N. Nitrogen balance was markedly improved (p less than 0.001) in the enteral-fed group. Although visceral protein markers and overall complication rate were not significantly different, septic morbidity was greater (p less than 0.025) in the control group (abdominal infection in seven and pneumonia in two) compared to the enteral-fed patients (abdominal abscess in three). Analysis of patients with A.T.I. 15-40 disclosed sepsis in seven (26%) of the control versus one (4%) of the enteral-fed group (p less than 0.01). Our clinical experience demonstrates the feasibility of immediate postoperative enteral feeding via N.C.J. after major abdominal trauma, and suggests this early nutrition reduces septic complications in critically injured patients. PMID- 3095558 TI - Enteral versus parenteral nutritional support following laparotomy for trauma: a randomized prospective trial. AB - Although enteral nutrition is considered more 'physiologic' than parenteral nutrition, there is greater published experience with parenteral nutrition in trauma patients. To compare the efficacy of these two techniques, we prospectively randomized multiple trauma patients during their admission laparotomy to receive either central venous parenteral nutritional (TPN: n = 23) or enteral nutrition by jejunostomy (Jej: n = 23). Nutritional support began on the first postoperative day; the study period continued a maximum of 14 days. There were no significant differences between the two groups in age, sex, injury severity, estimated caloric needs (3,322 TPN; 3,114 Jej), hours to achieve full prescription (77 PTN; 79 Jej), or the number of days on nutritional support (22 TPN; 25 Jej). Average daily caloric intakes, nitrogen balance results, and complication rates were also comparable. These results suggest that early postoperative jejunostomy feeding is a safe and efficacious choice for multiple trauma patients undergoing laparotomy. PMID- 3095559 TI - Antibodies of patients infected with Schistosoma japonicum crossreact with diagnostic proteins of Schistosoma mansoni. PMID- 3095560 TI - Serodiagnosis of intestinal tuberculosis by the soluble antigen fluorescent antibody test (SAFA test). AB - The diagnosis of intestinal tuberculosis can only be established by the tissue obtained during surgery or endoscopy. We investigated the role of the soluble antigen fluorescent antibody (SAFA) test with the possibility that it may prove to be a valuable technique for the serodiagnosis of intestinal tuberculosis. The sera of 38 patients and 60 control subjects were studied. Mycobacterial saline extract was used as an antigen in the test. Thirty-two (84%) of 38 patients with intestinal tuberculosis yielded positive values (fluorescence coefficient greater than 3). Among the control subjects a false positive result was observed in only one patient who had eosinophilic enteritis. Patients with intestinal tuberculosis had a significantly higher level of antibodies than patients with non-tuberculous intestinal disease and healthy subjects. These results suggest that this technique may be used for the diagnosis of intestinal tuberculosis and in differentiating it from other non-tuberculous intestinal diseases. PMID- 3095561 TI - Ultrasonography of pancreatic schistosomiasis: a case report. AB - A 10 year old girl presented with fever, pain, anaemia, hepatosplenomegaly and eosinophilia. No schistosomal ova were found on stool examination. Abdominal ultrasound revealed a mass in front of the portal vein conforming to the shape of an enlarged pancreas. Laparotomy revealed a firm, granular, whitish mass involving the pancreas. Examination of biopsy samples showed granulomata of Schistosoma mansoni in the pancreas, liver and lymph nodes. The patient responded to therapy with oxamniquine. PMID- 3095562 TI - The effects of Schistosomiasis haematobium on the activity of school children. AB - Schistosomiasis haematobium is prevalent in many parts of Africa, especially among school-age children. It is thought to cause lethargy, but the effect may be masked by the selective exposure of more active children to the disease. Infected children at a primary school in an endemic area in South Africa were used as their own controls in a before-and-after treatment study. Energetic activity was monitored by means of electronic meters before treatment, and at 3 and 6 months after treatment with an antischistosomal drug. Results indicated that the scores of treated children had increased significantly relative to the untreated controls, and that there were differences between the sexes in the change of activity level. PMID- 3095563 TI - A pilot study of mitomycin-C/5-fluorouracil infusion combined with split course radiation therapy for carcinomas of the larynx and hypopharynx. AB - Fifty-seven patients with advanced squamous carcinoma of the larynx and hypopharynx were entered on a pilot study of initial therapy using split course radiation therapy combined with simultaneous chemotherapy using mitomycin-C and 5 fluorouracil. The treatment was well tolerated with 90% of patients completing their planned radiation treatment. Seventy percent of this group completed their planned chemotherapy. Significant hematological toxicity was not observed. Survival and loco regional control at one and two years of follow-up were considered at least comparable to that achieved with conventional single-course radical radiation therapy as primary treatment. Based on these results a randomized trial of this radiation-chemotherapy regimen compared to radiation therapy alone as initial therapy is in progress. PMID- 3095564 TI - Vesical diverticulum associated with bladder carcinoma: therapeutic implications. AB - Of 146 patients with bladder diverticula during a 15-year period 9 had associated transitional cell carcinoma of the bladder: 3 (2 per cent of all patients with diverticula) in the diverticulum, 3 adjacent to the ostium of the diverticulum and 3 remote from the diverticulum. All 3 patients with carcinoma in the diverticulum died of metastases, whereas the other 6 patients survived more than 5 years. We propose aggressive treatment for patients with carcinoma in the diverticulum but we do not recommend routine diverticulectomy in cases of asymptomatic and uncomplicated diverticula. PMID- 3095565 TI - Elevated prostatic acid phosphatase: a prognostic factor for stage C adenocarcinoma of the prostate. AB - The clinical course of 25 patients with clinical stage C adenocarcinoma of the prostate who had pre-treatment elevations of the prostatic acid phosphatase (Roy test) was analyzed retrospectively. All patients were treated with definitive external beam radiation therapy at our hospital between 1974 and 1980. Of the 25 patients 17 (68 per cent) have had disease progression. The median time to treatment failure for this group was 27 months (range 10 to 101 months), and the over-all median survival for these patients has not been reached (range 16 to 120 months). Local control of disease was achieved in 84 per cent (21 of 25) of the patients. The control group consisted of 75 consecutive age-matched patients with normal pre-treatment prostatic acid phosphatase levels whose disease was identically staged and treated at our hospital from July 1977 to January 1979. The median time to disease progression in this group has not yet been reached. Of these 75 patients 24 (32 per cent) have had disease progression within a median time of 38 months. Therefore, an elevated pre-treatment prostatic acid phosphatase value is a harbinger of systemic disease and indicates that radiotherapy will be significantly (p equals 0.002) less effective as a definitive local therapeutic modality. PMID- 3095566 TI - Pre-treatment testosterone levels: significance in androgen deprivation therapy. AB - From June 1982 to February 1985, 53 patients with stage D2 carcinoma of the prostate confirmed by tissue biopsy, elevated prostatic acid phosphatase and a positive bone scan were initiated on androgen deprivation therapy. Before commencement of treatment all patients underwent determination of serum testosterone levels at 8 a.m. Of the patients 23 received 200 mcg. buserelin per day, 17 received 1 mg. diethylstilbestrol 3 times daily, 6 received 40 mg. megestrol acetate 4 times daily, 2 received 1 mg. leuprolide per day and 5 underwent bilateral orchiectomy. Evaluation of the best response in each patient revealed 3 (6 per cent) complete and 17 (32 per cent) partial responses, while 22 patients (41 per cent) remained stable and 11 (21 per cent) had progression. Pre treatment serum testosterone levels ranged from 150 to 879 ng. per dl. The mean serum testosterone level in patients having a complete response was 524 +/- 18.04 ng. per dl. The mean in the progression group was 279.4 +/- 110.1 ng. per dl. This difference was not statistically significant owing to the large standard deviation in the progression group. However, of the 15 patients who had a pre treatment serum testosterone level of more than 500 ng. per dl. only 1 (7 per cent) had progression. None of the patients whose pre-treatment testosterone level was less than 200 ng. per dl. had objective tumor regression. Our study suggests that pre-treatment serum testosterone levels may predict the probability of a satisfactory response to androgen deprivation therapy. PMID- 3095567 TI - Diverticula of the ductus epididymis in men. AB - The histological study of epididymides obtained from autopsies (41 children, 7 young adults and 8 elderly men) and surgical specimens (10 young adults and 3 elderly men) revealed the presence of multiple diverticula in the cauda epididymis in all elderly men and in only 2 young adults (32 and 33 years old). The diverticula appeared as evaginations of the epithelial lining of the duct, disrupting the muscular coat and expanding into the surrounding connective tissue. The formation of epididymal diverticula seems to be an age-related process that might be caused by repeated increases in the intraluminal pressure in the cauda epididymis. PMID- 3095568 TI - Effect of nitroglycerin on ventricular oxygen extraction during aortic occlusion. AB - Nitroglycerin (NTG) is often administered to improve hemodynamics during aortic occlusion (AO). This investigation was designed to characterize the effect of NTG on left ventricular oxygen extraction during thoracic aortic occlusion. Open chest dogs (n = 12) underwent measurement of mean arterial pressure, heart rate, and coronary blood flow. The great cardiac vein (GCV) was cannulated. AO was produced by a balloon in the descending aorta. Arterial and GCV oxygen content were determined before, 30 seconds, and 10 minutes after AO (control occlusions). Oxygen extraction (A-V)O2, oxygen consumption, and cardiac work were calculated. AO was repeated during NTG infusion (2 micrograms/kg/min IV) in seven animals. (A V)O2 was decreased 10% at 30 seconds in control occlusions. NTG exacerbated these decreases in oxygen extraction. With NTG, (A-V)O2 decreased by 33% despite a 12% increase in cardiac work. The fact that early decreases in oxygen extraction occurring after AO are accentuated by NTG may predispose patients undergoing aortic reconstruction who receive NTG to myocardial ischemia. PMID- 3095569 TI - The method of determination must be considered in interpreting blood cholesterol levels. AB - Based on the results of recent clinical trials, physicians have been encouraged to screen and treat patients for hypercholesterolemia. Since the data from the Lipid Research Clinics (LRC) have been used to define the patient population that should be treated, a comparison of LRC cholesterol results with those obtained with two commonly used clinical laboratory instruments was performed. Both the Technicon SMAC and the Du Pont aca had positive bias compared with the LRC method. Therefore, many patients with cholesterol concentrations greater than 265 mg/dL (6.85 mmol/L) as determined by these routinely used methods have markedly lower levels determined by LRC methods. These findings not only indicate that rigorous interlaboratory standardization is required to conform to LRC reference values, but they also suggest that the clinician should be aware of these methodological considerations when the decision to treat hypercholesterolemia is made. PMID- 3095570 TI - Humoral autoimmune response to rat male accessory glands. Comparative specificity studies of auto and heteroantibodies. AB - A comparison of specific antibodies induced by a saline extract of chemically modified rat male accessory glands (MRAG) in isologous (male and female rats) and heterologous animals (rabbits and a goat) was made. This study was focused on the specificity of the antibodies confronted with saline extract of rat male accessory glands (RAG), their Sephadex G-100 fractions and autoantigen fragments. Specificity studies with Sephadex G-100 fractions of RAG showed that whereas in male rats only the antibodies reactive with Fraction 1 containing autoantigens were detected, one additional population of antibody with different specificity was revealed in female sera. In contrast, antibodies against several other macromolecules were present in heterologous sera. When analyzed for the serum specificity against three enzymatic fragments of autoantigen, the main specificities of male and female sera were different. PMID- 3095572 TI - Immunoelectrophoretic demonstration of Rho(D) antigen of red blood cell membrane. PMID- 3095571 TI - Improved hemagglutination and hemagglutination-inhibition tests for Akabane virus using formalinized goose erythrocytes. AB - When formalinized instead of fresh goose erythrocytes were used in the hemagglutination (HA) test system of the Akabane virus, the agglutinability of the erythrocytes increased and became less salt-dependent. The improved method based on these findings should facilitate the hemagglutination-inhibition (HI) test and may be useful for epidemiological studies of the Akabane virus. PMID- 3095573 TI - Blood group specificity of an autohemagglutinin induced by alpha-methyldopa therapy. PMID- 3095574 TI - The effect of double filtration plasmapheresis on thyroid hormone economy and thyroid function. AB - Five cases of rheumatoid arthritis (RA), two cases of systemic lupus erythematosus (SLE), a case of mixed connective tissue disease (MCTD), and a case of cold urticaria were treated with double filtration plasmapheresis (DFP). Each aliquot of plasma was obtained at three different points of the DEP circuit during the treatment and concentrations of thyroid hormones as well as thyroxine binding globulin (TBG) were measured. Despite the removal of considerable amounts of triiodothyronine (T3), thyroxine (T4), and TBG from the plasma, levels of plasma free T3 (FT3) and free T4 (FT4) before and immediately after DFP treatment were not significantly different. These results indicate that DEP therapy rarely affects plasma concentration of active thyroid hormones in patients who undergo such therapy. PMID- 3095575 TI - Difference in the effects of acetazolamide and ammonium chloride acidosis on ventilatory responses to CO2 and hypoxia in humans. AB - The effects of acetazolamide, a potent carbonic anhydrase inhibitor, and ammonium chloride (NH4Cl) on arterial blood gas tension, resting ventilation, and ventilatory responses to CO2 (HCVR) and hypoxia (HVR) were studied in healthy male subjects. Both drugs induced chronic metabolic acidosis with the reduction in plasma bicarbonate by a mean of 7.0 +/- 2.0 (S.D.) mM after acetazolamide and by 5.6 +/- 1.8 mM after NH4Cl. The ratio in the decrement of PaCO2 to that of plasma bicarbonate (delta PaCO2/delta [HCO3-]) was 1.51 in the former and 0.98 in the latter. Both drugs increased inspiratory minute ventilation (VI) predominantly due to increased tidal volume (VT) with acetazolamide and to increased respiratory frequency (f) with NH4Cl. In HCVR, the increments in CO2- ventilation slope and in ventilation at PETCO2 60 mmHg after drug administration were 0.77 +/- 0.51 l X min-1 X mmHg-1 and 20.0 +/- 11.2 l/min with acetazolamide and 0.59 +/- 0.40 l X min-1 X mmHg-1 and 8.0 +/- 2.8 l/min with NH4Cl, respectively. On the other hand, HVR both in terms of delta VI/delta SaO2 slope and of ventilation at SaO2 75% significantly increased after NH4Cl but not after acetazolamide administration. Thus, augmented VT and HCVR in the acetazolamide group and increased f and HVR in the NH4Cl group suggested that the central chemosensitive mechanism in the former and the peripheral chemosensitive mechanism in the latter may predominantly be responsible for the elevated ventilatory activities. PMID- 3095576 TI - Disturbance of CO2 elimination in the lungs by carbonic anhydrase inhibition. AB - Carbonic anhydrase in the red blood cell and in the pulmonary endothelium facilitates the elimination of CO2 in the lungs. Although a carbonic anhydrase inhibitor, such as acetazolamide which is frequently used in patients with glaucoma or with metabolic alkalosis, is known to impair the CO2 elimination in the lungs, the dose-response curve of CO2 elimination with acetazolamide has not been well documented in CO2 homeostasis. In the present study, the effects of inhibited carbonic anhydrase were tested in 8 anesthetized dogs; various dosages of acetazolamide were used. When the administered clinical dosage of acetazolamide increased from 5 to 20 mg/kg, PaCO2, PVCO2, arterial-alveolar PCO2 difference (a-ADCO2), and physiological VD/VT ratio increased progressively to 52.0 +/- 2.1 Torr, 58.0 +/- 3.0 Torr, 23.4 +/- 1.2 Torr, and by 19.2 +/- 1.8% (S.E.) respectively, whereas inhibition rate of red blood cell carbonic anhydrase (RCA) activity increased progressively to 73.1 +/- 2.1% (S.E.). On the other hand, PACO2 decreased to 27.1 +/- 1.8 Torr (S.E.) upon the first injection of 5 mg/kg of acetazolamide, but PACO2 did not change further upon 3 additional 5 mg/kg injections. Mixed venous-arterial PCO2 difference [V-a)PCO2), VCO2, and anatomical VD/VT ratio were unchanged by the administration of any doses of acetazolamide. PMID- 3095577 TI - Prediction of individual tumor chemosensitivity in subrenal capsule assay. AB - Fifty-three tumor specimens, including thirty-one stomach and seven esophageal cancers, were examined to determine the individual tumor sensitivity to chemotherapeutic agents. Using the subrenal capsule assay (SRC assay), tumor specimens were implanted under the renal capsule of male, 8 week old ddY mice, after cutting the tissues into 1.5 mm cubed fragments. Following the implantations, chemotherapeutic agents were injected daily for 3 days and the relative variations of tumor weights were calculated. An 84.9 per cent of the total evaluability rate was obtained and implanted tumor specimens responded to chemotherapeutic agents in 26.7 per cent. The correlation rate between tumor sensitivity in SRC assay and clinical responses was obtained in 72.9 per cent. The predictive accuracy rate of the clinical responses was 50.0 per cent, while 100 per cent of the prediction rate of clinical resistance was obtained. With regard to upper gastro-intestinal cancers, 83.9 per cent of the evaluability rate and 18.2 per cent of response rate in SRC assay were obtained. These results indicate that this assay is equivalent to other procedures for predicting individual tumor sensitivity. PMID- 3095578 TI - [Use of Pseudomonas aeruginosa multicomponent vaccine in patients with intractable lower respiratory tract infection associated with diffuse panbronchiolitis]. PMID- 3095579 TI - [Pre-operative one-shot intra-arterial infusion chemotherapy of bladder cancer. 1. Experimental studies on the selection of drugs]. PMID- 3095580 TI - Human primary colon carcinomas xenografted into nude mice. II. Modulation of tumor plasminogen activator activity by the host tissue environment. AB - The characterization and quantitation of plasminogen activators (PAs) expressed by human colon carcinoma cell lines and primary colon carcinomas inoculated into nude outbred (nu/nu) mice, either as subcutaneous or gut-implanted (GI) xenografts, were discussed. The two colon carcinoma cell lines used in this study, Col 112 (moderately differentiated) and Col 115 (poorly differentiated), differ in their PA expression, the former being a urinary-type PA and the latter being a tissue-type PA producer. Both cell lines demonstrate a positive correlation between tumor invasiveness and measured PA activity; subcutaneous xenografts growing as noninvasive pseudobenign tumor masses were associated with low levels of PA activity, whereas GI xenografts exhibiting invasive growth expressed higher PA activity. Furthermore, coinoculation of Col 115 tumor cells sc and GI in the same host induced high levels of PA activity in subcutaneous xenografts, suggesting a stimulatory effect of the GI xenograft on subcutaneous xenograft PA expression. Also, purified murine plasminogen was demonstrated to represent an efficient substrate for tumor-secreted human PA. PMID- 3095582 TI - A backpack system for long-term osmotic minipump infusions into unrestrained marmoset monkeys. AB - A backpack system is described whereby osmotic minipumps are used to infuse gonadotrophin-releasing hormone (GnRH) subcutaneously in a pulsatile manner into infertile socially subordinate female marmoset monkeys (Callithrix jacchus jacchus). This procedure enables long-term infusion of GnRH without the necessity of repeated subcutaneous implantation of pumps and GnRH reservoirs. The backpack and cannulae system is inexpensive and can be constructed from commonly available materials. The GnRH treatment successfully overcame the suppression of pituitary luteinizing hormone secretion imposed by the low social status of female marmoset monkeys. PMID- 3095581 TI - Gonadotropin, steroid, and thyroid hormone milieu of young SWR mice bearing spontaneous granulosa cell tumors. AB - Young SWR mice possessing spontaneous ovarian granulosa cell (GC) tumors were examined for evidence of endocrine dysfunction associated with tumorigenesis. Tissue levels of hormones in tumor host and normal control females were measured by radioimmunoassays, ovarian luteinizing hormone (LH) receptors by uptake of 125I-labeled human chorionic gonadotropin (hCG) administered iv, and ovarian 3 beta-hydroxysteroid dehydrogenase (3-beta-OH) activity by histochemical techniques. When data from tumor host mice were compared with control data, hypothalamic gonadotropin releasing hormone content was not significantly different. Pituitary LH and follicle-stimulating hormone (FSH) contents were significantly decreased. Serum FSH, but not LH, levels were significantly reduced. No specific uptake of 125I-labeled hCG by tumor tissue was detected, whereas uptake by nontumorous contralateral ovaries was identified and found to be similar to that of control ovaries. With respect to serum steroids in tumor host mice, progesterone, dihydrotestosterone, and testosterone were significantly reduced, whereas androstenedione, dehydroepiandrosterone, corticosterone, estrone, and estradiol were normal. Frozen sections of tumor tissue failed to show any 3-beta-OH activity, whereas prominent activity was observed in non tumorous contralateral and control ovaries. Serum thyroxine levels, evaluated because of the known depressive effects of hypothyroidism on reproductive function, were found to be significantly elevated in tumor host mice. The above results suggest that in SWR mice with spontaneous GC tumors, gonadotropins are moderately suppressed; the granulosa tumor cells do not have LH-hCG receptors; steroidogenesis by tumor tissue is reduced, whereas peripheral conversion of adrenal androgen precursors to estrogens is normal; and elevated serum thyroxine levels have a secondary role in established GC tumors. PMID- 3095584 TI - Annual meeting of the Society for the Study of Inborn Errors of Metabolism. Liverpool, 3-6 September 1985. PMID- 3095583 TI - Enteral perfusion in the pig. AB - Techniques for the insertion of catheters in the colon of piglets following simple laparotomy were developed to facilitate an in vivo study of colonic absorption. Catheters were tunneled subcutaneously to a dorsal parascapular position from which the colon could be intermittently (or continuously) perfused with test solutions without physical or chemical restraint. Because of the pig's unique body habitus, the catheter is not likely to be removed by the animal. We have demonstrated in four pigs that they can be maintained free of systemic sepsis for up to 2 weeks, allowing for regular intermittent administration of fluids. PMID- 3095585 TI - Maternal phenylketonuria. AB - Pregnant women with untreated phenylketonuria (PKU) with blood phenylalanine levels greater than 1200 mumol/L usually give birth to offspring with congenital birth defects, including microcephaly, cardiac defects and mental retardation. According to Mabry and Levy, hyperphenylalaninaemic (HPA) women with blood phenylalanine levels between 600 and 1200 mumol/L also have an increased risk to their offspring. To study this problem further, the National Institute of Child Health and Human Development has established a collaborative study for 7 years to elucidate a proper treatment programme for these women. PMID- 3095586 TI - Diagnosis in relationship to treatment of hyperphenylalaninaemia. AB - PKU is not a single simply defined entity. It is part of a spectrum of the hyperphenylalaninaemias. Natural protein loading studies with uniform Phe equivalents are simple, and they are an inexpensive and safe way to determine or categorize the types of hyperphenylalaninaemias (excluding defects of biopterin). Evidence from the US PKU Collaborative Study indicates that all patients with PKU do not require indefinite or prolonged restrictive dietary therapy to maintain normal intellectual functioning. Although there are as yet no absolute criteria, it appears that the milder forms of PKU may need treatment for a shorter period of time. PMID- 3095587 TI - Cancer care and prospective payment: primum non nocere. PMID- 3095588 TI - Bioprosthesis in hand surgery. AB - In 1965, Carpentier coined the term bioprosthesis to distinguish the characteristics of glutaraldehyde-treated porcine heart valves from untreated or synthetic valves. Observation that the valves functioned normally but were not incorporated by the host has stimulated interest in similarly preserved materials for use in hand surgery. This report outlines work that was initiated to learn the effects of glutaraldehyde treatment on tendon and a reticular substitute. In over 56 experiments with a chicken model, experience with glutaraldehyde-treated tendon grafts shows no acute rejection. There is good function clinically by 8 weeks with proximal fibrous ingrowth seen histologically. By 12 weeks, distal ingrowth has occurred. There is no ingrowth into the tendon graft within the fibro-osseous tunnel. Mechanical testing of the implant system shows a peak load at failure of 1.86 +/- 0.43 pounds and at 24 weeks it is 6.53 +/- 2.6 pounds. The failure site at time zero was distal. By 12 weeks, the distal attachment strengthened and the proximal attachment failed at a greater load. An interpositional substance with potential uses in hand surgery has been prepared by glutaraldehyde treatment of mammalian pericardium. Possible uses include interposition between fractured phalanx and the extensor tendon. This has been evaluated in feasibility studies in a rabbit model. PMID- 3095589 TI - The effects of high-nutrient urea on in vitro bullfrog fundic mucosa. AB - The effects of nutrient urea (240 mM) on H+ secretion, potential difference, and resistance were studied in isolated sheets of bullfrog fundic mucosa. H+ secretion was significantly reduced while transmucosal resistance was significantly increased and potential difference was significantly decreased. Measurement of CO2 utilization by, and distribution across, the mucosal sheets demonstrated that oxidative metabolism is increased (tCO2, 4.93 +/- 0.2 to 5.83 +/- 0.3 mumole/cm2 hr-1, P less than 0.05) and that generation of protons (H+) within the oxyntic cell is stimulated (delta CO2, 1.48 +/- 0.1 to 2.22 +/- 0.2 mumole/cm2 hr-1, P less than 0.05, and nutrient HCO-3 1.35 +/- 0.2 to 2.21 +/- 0.2 mueq/cm2 hr-1, P less than 0.05) in spite of paradoxically diminished H+ appearance on the secretory surface. Studies using 120 and 60 mM urea suggest that the effects may be dose dependent. Results with 240 mM sucrose on the nutrient surface would indicate that those seen with urea cannot be attributed entirely to the hyperosmolality. Pretreatment of the mucosal sheets with metiamide (10(-3) M) resulted in the expected decrease in titratable H+ (to 0) but had no effect on urea-stimulated oxidative metabolism (tCO2, 2.09 +/- 0.2 to 2.91 +/- 0.4 mumole/cm2 hr-1, P less than 0.02) or the generation of protons by the oxyntic cell (delta CO2, 0.68 +/- 0.1 to 1.35 +/- 0.3 mumole/cm2 hr-1, P less than 0.02, and nutrient HCO3- 0.83 +/- 0.1 to 1.65 +/- 0.3 mueq/cm2 hr-1, P less than 0.05). Both simultaneous or subsequent treatment with theophylline (5 X 10( 3) M) reversed the inhibitory effect of urea on H+ secretion. Transmission electron microscopy revealed involution of the secretory membrane following treatment with urea but maintenance of the microvillous secreting configuration of the membrane when theophylline was added to the nutrient solution. These results suggest that although nutrient urea stimulates the generation of H+ within the cell it simultaneously inhibits release of H+ by the secretory membrane. Failure to inhibit urea-stimulated generation of H+ within the cell by metiamide indicates that the increased oxidative metabolism and generation of protons stimulated by nutrient urea is probably not histamine-mediated. It is suggested that urea inhibits adenylyl cyclase and thus cAMP-mediated evolution of the secretory membrane with reduced H+ transport, an effect that can be reversed by inhibiting phosphodiesterase with theophylline. PMID- 3095590 TI - Continuous administration of pharmacological agents in heterotopically transplanted hearts. AB - A modification of the intraabdominal heterotopic heart transplantation model in rats is described which enables the local administration of pharmacological agents by means of a mini osmotic pump. In this modification, the aortic arch of the donor heart is cut after junction of the left carotid artery to enable the introduction of a catheter in the innominate artery. This catheter is connected to an implantable mini osmotic pump which delivers a continuous flow for 7 days. Radiographs of transplanted animals bearing pumps filled with a contrast agent showed that the coronary vessels of the graft were effectively perfused. Furthermore, continuous perfusion of prednisolone into the graft appeared to be as effective as subcutaneous infusion. Additional information about the usefulness of this perfusion technique is provided by recent data indicating that the expression of MHC class II antigens on vascular endothelium of a graft could only be evoked by interferon-gamma when it was locally administered into the graft. Our results demonstrate that this technique is suitable for investigating the effects of local, continuous administration of pharmacological agents on heart grafts. PMID- 3095591 TI - Glucocorticosteroid regulation of prostaglandin biosynthesis in human myometrial smooth muscle cells in monolayer culture. AB - In the present investigation, we evaluated the production of prostaglandins by human myometrial smooth muscle cells maintained in monolayer culture in the absence or presence of glucocorticosteroids. In the presence of cortisol (10(-7) M) or dexamethasone (10(-8) M), the rate of production of prostacyclin (PGI2) by these cells was decreased significantly. The glucocorticosteroid-mediated inhibition of prostaglandin production was attenuated when cortisol-21-mesylate (10(-6) M), a glucocorticosteroid antagonist, was present in the culture medium. The rate of conversion of radiolabeled arachidonic acid to radiolabeled prostaglandins as determined by use of sonicates of myometrial cells and optimal assay conditions, however, was not affected significantly by treatment with cortisol or dexamethasone in concentrations sufficient to inhibit prostaglandin formation by more than 80%. These findings are suggestive that glucocorticosteroids act in human myometrial smooth muscle cells in culture to inhibit prostaglandin formation by way of a receptor-mediated process that does not involve inhibition of enzyme activities that are involved in the biosynthesis of prostaglandins, i.e. the conversion of arachidonic acid to prostaglandin. PMID- 3095592 TI - Pathogenesis and characteristics of spontaneously metastasizing mammary carcinomas and the general principle of metastasis. AB - Chemical mammary carcinogenesis in immunologically attennuated W/Fu female rats, subjected to specific and nonspecific immunostimulations, yielded many spontaneously metastasizing adenocarcinomas with varying degrees of glandular differentiation, and growth rates. The pathogenesis of these tumors suggested that while carcinogens transform target cells, the host immune system endows them with metastatic potential. The metastatic pathways were recognizable as hematogenous, lymphogenous, or hematogenous-lymphogenous combined, according to the capacity of the tumor cells to intravasate the lymphatic and/or vascular channel and traverse the pulmonary artery. The same metastatic pattern can be reproduced with cells from any of the organs involved, indicating that it is inherent in all cells within a given tumor, rather than being determined by the organs they colonize. The biological, biochemical and immunological characteristics of these tumors resemble human breast cancer thus becoming an effective tool in the formulation of the general principle of metastasis by malignant solid tumors. PMID- 3095593 TI - Home parenteral nutrition for patients with advanced intraperitoneal cancers and gastrointestinal dysfunction. AB - The use of total parenteral nutrition (TPN) in patients with advanced, untreatable cancer is controversial. Occasionally, however, damage to bowel by tumor, radiation, or surgery renders these patients unable to eat and TPN may be indicated to prevent premature death from starvation. We have used Home Parenteral Nutrition (HPN) to support three patients with advanced, untreatable abdominal cancer and inability to eat. Morbidity was minimal and survival times were 24, 6 and 1.5 months. Payment was covered by third party agencies. All patients and their families were gratified by the ability to return home with nutritional support. HPN can be used to support terminal cancer patients with bowel obstruction and may afford them longer survival. Ideally, patients considered for this should be well motivated, with good support systems, and with survival estimated to be at least months. PMID- 3095594 TI - Continuing care retirement communities. PMID- 3095595 TI - Residential care. PMID- 3095596 TI - Legislation related to Alzheimer's disease. PMID- 3095597 TI - Treatment of primary hyperhidrosis. AB - Primary hyperhidrosis is a physically and emotionally distressing condition. Physicians should be aware of the various treatment modalities available for controlling or reducing the profuse sweating, which involves mainly the palms, soles, and axillas. The simplest methods, such as topical application of aluminum chloride, should be attempted first. If topical medications are ineffective, iontophoresis may provide relief, especially in patients with plantar or palmar involvement. When patients are unresponsive to other treatment options, surgical intervention may be warranted-excision of sweat glands in patients with axillary hyperhidrosis and upper thoracic sympathectomy in those with palmar involvement. Although excellent results have been reported, complications and resumption of sweating have occurred. PMID- 3095598 TI - Mast cell leukemia: report of a case and review of the literature. AB - We report the clinical and pathologic findings in one case of mast cell leukemia observed in a series of 60 patients with systemic mast cell disease. The leukemic variant of systemic mast cell disease is rapidly fatal (mean duration of survival, less than 6 months) in contrast to most nonleukemic cases, which follow an indolent clinical course. On the basis of our case and eight previously reported cases, mast cell leukemia is characterized by a substantial increase in atypical mast cells in the peripheral blood, diffuse infiltration with atypical mast cells in the bone marrow, a strong association with peptic ulcer disease, prominent constitutional symptoms, and hepatosplenomegaly. These cases should be distinguished from malignant mastocytosis without a substantial number of circulating atypical mast cells and also cases of acute nonlymphocytic leukemia that arise in the background of systemic mast cell disease. PMID- 3095599 TI - Effects of meclofenoxate and Extr. Rhodiolae roseae L. on electroconvulsive shock impaired learning and memory in rats. AB - In experiments on albino rats, the authors studied the effects of meclofenoxate and Extr. Rhodiolae roseae on the memory-impairing action of convulsant electroshock. "Step-down" passive avoidance training with negative reinforcement was used to trace the changes in memory. Meclofenoxate administered i.p. in a dose of 100 mg/kg body weight for five days prevented the retrograde amnesia observed after convulsant electroshock upon retention testing on the 3rd and 24th hr after the end of the training session. The Rhodiola extract administered orally in a dose of 0.10 ml/rat for 10 days, which in other experimental approaches improved learning and memory, remained ineffective here. The role of biogenic monoamines in the learning- and memory-improving effects of meclofenoxate is considered on the basis of earlier studies by the authors. PMID- 3095600 TI - [Intravenous feeding via central venous catheter caused bilateral pleural effusion]. PMID- 3095601 TI - Depletion of norepinephrine in mouse heart by 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) mimicked by 1-methyl-4-phenylpyridinium (MPP+) and not blocked by deprenyl. AB - A single dose of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in mice caused 75-87% depletion of heart norepinephrine (NE) concentration 24 hrs later. MPP+ (1-methyl-4-phenylpyridinium) caused similar depletion of heart NE. The effect of MPTP was not blocked by pretreatment with deprenyl, an inhibitor of type B monoamine oxidase (MAO-B). Also, deprenyl pretreatment did not prevent the depletion of heart NE after 4 daily doses of MPTP, even though in the same mice deprenyl pretreatment did prevent depletion of dopamine in the striatum and of NE in the frontal cortex. Apparently the depletion of heart NE by MPTP, unlike the depletion of brain catecholamines, does not require that MPTP be metabolized by MAO-B and can be mimicked by systemic injection of MPP+. PMID- 3095602 TI - Nonchelational cell growth inhibition by EDTA. AB - The ability of the dinitrilotetraacetates EDTA, CDTA, and EGTA to inhibit the growth of rat C6 glioma cells was not proportional to their chelational stability constants, suggesting a nonchelational mechanism of action. Ion antagonization studies supported this hypothesis. Growth inhibition did not appear to be caused by an EDTA-ion coordination complex. The chemical structure of the DNTAs suggests that they might act by: increasing zeta potential electronegativity and altering local physical properties; macromolecular crosslinking; and disrupting hydrogen bonds and hydrophobic interactions. Interestingly, their ability to inhibit growth paralleled their hydrophobic surface areas. PMID- 3095603 TI - The blood hepatocytic barrier: a light microscopical, transmission- and scanning electron microscopic study. AB - The normal blood hepatocytic barrier (BHB), comprised by the endothelial lining cells and the perisinusoidal space, was investigated, and it was concluded that the BHB is a complex structure in which each individual part serves several functions. Immunohistochemical staining for factor VIII showed endothelial lining cells to be positive. By TEM and SEM the endothelial cells were seen to be fenestrated without a basal lamina. They possess numerous endocytotic vesicles. The perisinusoidal space contains the lipocytes and a matrix composed of fibrils, and a microfilamentous to granular material. The nature of these matrix components was poorly analyzable by conventional methods. Lipocytes were visualized by LM in: sections stained with oil red 0 after fixation in Baker's formol-calcium and following post-fixation in dichromate, and toluidine-blue stained Epon-embedded sections. TEM revealed numerous cytoplasmic processes rich in microfilaments encircling the sinusoids. PMID- 3095604 TI - Challenges for cost-effectiveness research. PMID- 3095606 TI - Effect of high ambient temperature on the lipids and on the activity of enzymes of rat liver microsomes. AB - The work has been aimed at determining the content of cholesterol and selected phospholipids (phosphatidyl choline, phosphatidyl ethanolamine, phosphatidylserine, and phosphatidylinositol) in rats' liver microsomes subjected to single and repeated exposure to an increased ambient temperature. Simultaneously, under the same experimental conditions, NADH activities--cyt. c. reductase and glucoso-6-phosphatase-in liver microsomal fractions were determined. In the experiments--a thermal chamber with controlled temperature, continual airflow and controllable humidity coming to 47-65% was used. Rats were subject to 6-hr exposure to the temperature of 21 degrees C, 28 degrees C, and 35 degrees C singly or for 3 and 6 consecutive days. In the experimental arrangements applied, no significant changes in the content of test phospholipids and cholesterol were found. The slight increase in the PC/PE relation under the effect of 28 degrees C and 35 degrees C for 6 consecutive days was not statistically significant. Cholesterol content in rats subjected to 35 degrees C for 6 days, 6 hrs daily, was higher--compared to the control group exposed to 21 degrees C--by about 15%, this differences being not statistically significant, either. The activities of NADH: cyt. c. reductase and glucoso-6-phosphatase in result of rats' single, 3- or 6-fold exposure to an increased temperature exhibit a level approximating the activity of those enzymes in controls. The lowest activities were observed in rats subjected to 35 degrees C for 6 consecutive days, 6 hrs daily.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095605 TI - A cost-effectiveness analysis of cyclosporine in cadaveric kidney transplantation. AB - Expected costs and health outcomes associated with cadaveric kidney transplantation using cyclosporine (CsA) plus steroids, azathioprine (Aza) plus steroids, and "dialysis only" were estimated from both a societal perspective and a Medicare perspective. Published data on patient and graft survival and treatment costs were incorporated into a Markov model to predict the ten-year experience of hypothetical cohorts of 1,000 35-year-old persons with end-stage renal disease (ESRD) exposed to each treatment option. In the base-case analysis conducted from the societal perspective, ten-year cumulative costs for the "dialysis only," CsA, and Aza cohorts were $181, $147, and $138 million, respectively. Transplantation using CsA rather than Aza would cost an estimated $19,800 per additional life-year and $9,700 per additional graft-year; whereas from Medicare's perspective, CsA would be less costly than Aza. This analysis suggests that under present regulations, widespread use of CsA instead of Aza for cadaveric graft recipients would result in significant cost shifting from Medicare to the private sector; but from a societal perspective, this would result in no, or at worst, relatively inconsequential, additional health expenditures. A policy whereby dollar savings achieved by Medicare from improved graft survival were used to help underwrite the cost of CsA for cadaveric kidney transplants would promote access to this drug and have little impact on the overall cost of care for individuals with ESRD. PMID- 3095607 TI - The WI-L2-729-HF2 human hybridoma system. Arrangement of lambda genes in monoclonal hybrids. AB - Fusion of WI-L2-729-HF2 human lymphoblastoid cells and human B-cell blasts provides a very efficient and rapid means of isolating stable B-cell hybridomas that secrete high levels of new human immunoglobulins. By titrating the plating density of fused cells into microwells immediately following fusion, it has been possible to obtain monoclonal hybrids. In this communication, proof of monoclonality is provided based on subcloning, karyotyping, and Southern blot analyses of lambda light chain immunoglobulin genes. The results reveal rearranged lambda genes in hybridoma subclones that produce both kappa (the WI-L2 729-HF2 isotype) and new lambda light chains. In contrast, the WI-L2-729-HF2 parental cell line and kappa-producing hybrids exhibit a germline configuration of lambda genes. The results provide evidence that stable, monoclonally derived hybridomas may be obtained upon initial plating of fused cells, without subsequent subcloning. The data further demonstrate the WI-L2-729-HF2 system to be ideal for rapidly generating, at very high frequency, clonal human B-cell hybridomas that stably secrete human monoclonal antibodies. PMID- 3095608 TI - Non-kinetochore directed autoantibodies in scleroderma/CREST. Identification of an activity recognizing a metaphase chromosome core non-histone protein. AB - Three scleroderma/CREST sera possessing anti-kinetochore autoantibody were tested by indirect immunofluorescence for reaction with isolated Chinese hamster metaphase chromosomes and histone-dissociated chromosome "scaffolds". All three sera revealed kinetochore staining on both whole chromosomes and histone dissociated chromosomes, and confirmed previous reports that the kinetochore is part of the chromosome scaffold. Unexpectedly, one serum also recognized a non centromere-located chromosomal antigen which is retained at the axial non-histone protein core following histone dissociation. The antigen is exclusively nuclear in origin, does not appear to be DNA or residual histone, and seems to correspond to a major component of the chromosome core. The existence of this antigen has important implications in terms of chromosome structure. Another CREST serum was shown to possess autoantibody against a cytoplasmic structural component, in addition to anti-kinetochore activity. The presence of anti-kinetochore and other autoantibody activities in CREST patient sera is discussed in relation to disease processes. PMID- 3095609 TI - Evaluation of Pseudomonas aeruginosa influence on the cytoskeleton of Hep-2 cells. AB - The cell cytoskeleton (microtubules, microfilaments and intermediate filaments) plays an important role in many cell functions, such as maintenance of cell locomotion, movement and compartimentalization of intracellular organelles and cell-to-cell interaction. Therefore, cytoskeleton alterations may result in sever impairment of cell functions. The aim of this paper was to study the in vitro effects of Pseudomonas aeruginosa on the cytoskeleton of cultivated Hep-2 cells. Cytoskeleton modifications were evidenced by immunofluorescence using monoclonal and polyclonal antibodies against tubulin and vimentin, and rhodamine conjugated phalloidin, that specifically binds to actin microfilaments. We report here that P. aeruginosa has a strong cytopathic effect on monolayers within a few hours of contact with the cells, and influences the organization of microfilaments, but has no discernable effect on microtubules or intermediate filaments. PMID- 3095610 TI - Effects of selenalysine on thialysine resistant CHO cells. AB - A thialisyne resistant variant clone of CHO cells also shows a lower sensitivity to selenasyne, the lysine analog containing selenium. Growth rate, cell viability and protein synthesis rate are less affected by selenasyne in the variant compared to the parental strain. Data are reported showing that during cellular growth of either strain some toxic derivatives of selenasyne are produced and accumulated in the culture medium even in the presence of excess lysine. PMID- 3095611 TI - Production and characterization of monoclonal strain-specific antibodies against prototype strains of Rickettsia tsutsugamushi. AB - We have developed 18 hybridoma cell lines which secrete murine monoclonal strain specific antibodies to prototype strains of Rickettsia tsutsugamushi: nine anti Gilliam, four anti-Karp and five anti-Kato antibodies. All the monoclonal antibodies reacted only with their homologous strains in direct and indirect immunofluorescence (IF), or indirect immunoperoxidase (IP) test. By IF and IP tests with the monoclonal antibodies, 22 strains of R. tsutsugamushi, which were newly isolated from mites, field rodents and patients with Tsutsugamushi disease (scrub typhus) in Japan, were all clearly identified as either Gilliam or Karp type. Analysis by polyacrylamide gel electrophoresis and immunoblotting techniques revealed that the monoclonal antibodies recognized primarily the polypeptides of an apparent molecular weight of 54 to 56 kilodaltons of the homologous rickettsial surface. The monoclonal antibodies produced in the present study should enhance the serotyping and further analytical investigation of the rickettsial antigens since they recognize the strain- or type-specific polypeptides and do not show any cross-reaction among strains. PMID- 3095612 TI - Immunological properties of Rickettsia tsutsugamushi, Kawasaki strain, isolated from a patient in Kyushu. AB - Nine isolates of Rickettsia tsutsugamushi were obtained from patients with Tsutsugamushi disease (scrub typhus) in Miyazaki Prefecture in Kyushu. Immunological analyses of these patients' sera and the isolates were performed by indirect immunofluorescence, indirect immunoperoxidase or immunoblotting techniques. In the analysis of reactions of the patients' sera with the prototype strains Gilliam, Karp, and Kato and with the isolates, sera from two patients, including Kawasaki, showed similar profiles and cross-reaction with the two isolates recovered from the corresponding patients, but reacted only weakly with the prototype strains. With guinea pig polyclonal antibodies against the isolate and prototype strains, Kawasaki strain showed some degree of cross-reaction with Gilliam strain but not with either Karp or Kato strain, nor with Shimokoshi strain which is known to be different antigenically from the prototype strains. Additionally, strain-specific murine monoclonal antibodies against Gilliam, Karp, and Kato strains did not react at all with Kawasaki strain. These results suggest that the Kawasaki strain may be different antigenically from the prototype strains and Shimokoshi strain. The finding two strains of the same antigenic type (Kawasaki) among only nine isolates suggests the presence of Kawasaki-type rickettsiae in Miyazaki Prefecture. Shimokoshi strain also did not react with these strain-specific monoclonal antibodies, suggesting that strains of R. tsutsugamushi antigenically distinct from the prototype strains, such as Kawasaki and Shimokoshi strains, may easily be recognized by their nonreactivity with these monoclonal antibodies. PMID- 3095613 TI - Transformation by extracellular DNA produced by Pseudomonas aeruginosa. AB - Most Pseudomonas aeruginosa strains are capable of producing extracellular DNA. Very closely linked chromosomal markers (leu+ and trp+) were co-transferred to P. aeruginosa PAO1819 (leu9001, trp9008) by the extracellular DNA produced by P. aeruginosa strains IFO3445 and PAO1 at a frequency of 10(-7) to 10(-8). Treatment of the extracellular DNA with DNase, heating at 95 C or sonication completely destroyed its transforming ability. The R plasmid in the extracellular DNA produced by P. aeruginosa IFO3445 (RP4) or PAO2142 (RLb679) could be transferred to Escherichia coli ML4901 or P. aeruginosa PAO1819. The resultant transformants showed identical resistance patterns in the respective donors, and the sizes of the DNAs of RLb679 and RP4 isolated from the transformants were the same as those in the respective donors. These results demonstrate that the extracellular DNA contains both chromosomal DNA and plasmid DNA, and that it exhibits transforming ability. This implies that transformation by the extracellular DNA produced by P. aeruginosa may occur in nature and this seems to be of clinical importance in view of the spread of R plasmids among pathogens. PMID- 3095614 TI - Toxicity and delayed type hypersensitivity caused by Microcystis blooms from Lake Kasumigaura. PMID- 3095616 TI - Diagnosis related groups. PMID- 3095615 TI - [Effect of surface-active agents on the electrical properties of bacterial cells]. AB - The work was aimed at studying the effect of cationic, anionic and non-ionogenic surfactants on the frequency dependence of the electroorientation effect (EOE) and on the electrophoretic mobility (EPM) of rod-like bacteria. The character of concentration dependences was found to differ for EOE and EPM at a low frequency of the electric field (20 to 10(4) Hz). Analysis of EOE changes at a high frequency (4 X 10(5) to 3 X 10(7) Hz) showed that anionic and non-ionogenic surfactants at a concentration up to 10(-3) M did not damage Escherichia coli, a Gram-negative bacterium, in contrast to Bacillus cereus, a Gram-positive bacterium. Cationic surfactants affected the cells of the both species. The optical properties of bacterial cells were found to change under the action of cationic surfactants. PMID- 3095617 TI - Diverticulosis of the vermiform appendix. AB - A case of appendicitis that was associated with a rare congenital diverticulum of the appendix is presented, along with the results of a retrospective study of diverticulosis of the appendix over a 10-year period. The incidence of the condition in this series (0.65%) is similar to other published series; however, two cases involved rare congenital diverticula--only 43 of such cases have been previously recorded in the medical literature world-wide. The average age of patients who present with acute appendicitis with acquired diverticula (37.8 years) is greater than that of patients without the condition. The perforation rate of an inflamed appendix when diverticula were present (27%) was higher than when no diverticula existed (6.6%). Because of the earlier and higher perforation rate, it is proposed that appendicectomy be performed if an appendix with diverticula is found during the course of a laparotomy for some other condition. PMID- 3095619 TI - Surveillance of hemophilia-associated acquired immunodeficiency syndrome. PMID- 3095620 TI - Imported paralytic poliomyelitis--United States, 1986. PMID- 3095622 TI - Update: influenza activity--Micronesia, United States. PMID- 3095621 TI - Plasmodium vivax malaria--San Diego County, California, 1986. PMID- 3095623 TI - Cholera in Louisiana--update. PMID- 3095618 TI - Multiple procaryotic ribonucleic acid polymerase sigma factors. PMID- 3095624 TI - Positive HTLV-III/LAV antibody results for sexually active female members of social/sexual clubs--Minnesota. PMID- 3095625 TI - Tuberculosis--United States, 1985. PMID- 3095626 TI - Trends in mortality from cirrhosis and alcoholism--United States, 1945-1983. PMID- 3095627 TI - Evidence for increased membrane permeability of plasmalemmal vesicles from livers of phenobarbital-induced CCl4-intoxicated rats. AB - We have observed a marked increase in Ca2+ permeability of plasma membranes isolated from rats treated in vivo with CCl4 (2 ml/kg), after phenobarbital induction and overnight fast. Regulation of intracellular free Ca2+ is vital to cell viability and function, and the increased plasma membrane permeability, if representative of a change occurring in vivo, may be a critical biochemical determinant of CCl4-induced hepatic necrosis. Permeability to small cations of liver plasma membrane vesicles of control and CCl4-dosed rats was tested by two independent methods: 1) Ca2+ efflux after passive loading in 1 mM Ca2+, and 2) 86Rb+ uptake driven by valinomycin-induced K+ diffusion potential after 100 mM KCl-equilibrated vesicles were stripped of external K+ by cation exchange. Both indicated markedly increased permeability in plasma membranes after CCl4 in vivo. First order rate constants of biphasic Ca2+ efflux were 0.272 and 0.0516 min-1 for controls and 1.78 and 0.171 min-1 for vesicles from CCl4-treated animals. 86Rb+ uptake by CCl4 vesicles was 47% of control. Total calcium contents of plasma membranes (prepared in the absence of EGTA) by atomic absorption were 17.4 +/- 2.0 (control) and 10.9 +/- 1.2 (CCl4) nmol/mg of protein (means +/- SE, p less than 0.025). In correlation with altered biochemical function, we found 4 fold increases in the content of 11-, 12-, and 15-hydroxyeicosatetraenoic acids in plasma membranes of CCl4-treated rats. Although these specific oxidized fatty acids are unlikely to be ionophores, the ionophoretic properties of certain other oxygenated polyunsaturated fatty acids suggest a mechanism whereby accumulation of lipid oxidation products may be responsible for the altered membrane permeability we have observed after CCl4, and perhaps ultimately for cell death in CCl4-induced hepatic necrosis. PMID- 3095628 TI - Fractionation of the beta subunit common to guanine nucleotide-binding regulatory proteins with the cytoskeleton. AB - Gs and Gi are guanine nucleotide-binding proteins that mediate the stimulation and inhibition, respectively, of adenylate cyclase. The extent to which the beta subunit common to these proteins may be associated with the cytoskeleton of S49 mouse lymphoma cells was assessed by procedures of differential detergent extraction and immunotransfer blotting. Treatment of cells with 1% Triton X-100 results in nearly quantitative extraction of cellular protein, phospholipid, tubulin, and the catalytic component of adenylate cyclase. Approximately 65% of the beta subunit is refractory to extraction. This population of the beta subunit, along with a population of actin presumed to originate from actin filaments, is subsequently solubilized with hypotonic medium containing 0.5% sodium deoxycholate and 1% Tween-40. The pattern of distribution of the beta subunit among sequential detergent extracts is corroborated by that of generated immunoreactive tryptic fragments. These results are consistent with the interaction of guanine nucleotide-binding proteins with the cytoskeleton. PMID- 3095630 TI - Perturbed hemopoiesis and the generation of multipotential stem cell clones in src-infected bone marrow cultures is an indirect or transient effect of the oncogene. AB - Multipotential stem cell lines, derived specifically from long-term bone marrow cultures infected with a recombinant retrovirus carrying v-src, lack v-src. Stable consequences thus result from transient actions or indirect effects of v src on other cells, with the latter possibility being favored by its mosaic expression in marrow cultures. PMID- 3095631 TI - IgG4 subclass deficiency syndromes. PMID- 3095629 TI - Purification and characterization of metallothionein from liver of cadmium exposed rhesus monkeys (Macaca mulatta). AB - Metallothionein (MT) a low molecular weight, Cd-binding, cysteine rich, cytosolic protein has been isolated, purified and characterized from cadmium exposed Rhesus monkeys maintained on protein calorie malnourished (PCM) diet. Metallothionein was resolved into three isoforms i.e. MTa, MTb and MTc. The ratio of Cd, Zn and Cu varied in these isometallothioneins. MTc was the major isometallothionein. U.V. Spectra of MTc revealed the presence of mercaptide bonds and absence of aromatic amino acids. These observations were further confirmed by amino acid analysis of MTc which demonstrated high cysteine content (22.6) followed by serine, glycine and lysine. The molecular weight of MTc as determined by gel filtration and amino acid analysis was 13,000 and 6398 daltons respectively. This demonstrates that MTc is a nonglobular ellipsoid polypeptide. MTc showed a unique property of binding selenium. Monkey liver metallothionein was immunologically identical with human metallothionein. All the characteristics of MTc obtained in the present study reveal a similarity between monkey and human metallothionein probably due to closer phylogenetic relationship between the two species. PMID- 3095632 TI - Familial deficiency of immunoglobulin IgA2. PMID- 3095633 TI - IgG subclasses in chimpanzees. PMID- 3095634 TI - [Nutrition of premature infants below 1,500 g: enteral prerequisites]. AB - The development of the human fetal gastrointestinal tract takes place early during gestation. The pancreas although developed by morphological means at the 16th week of gestation excretes its exocrine enzymes later at the 24th week of gestation except for amylase which reaches its full activity 6 months after birth. Trypsinogen secreted at the 24th week is activated into trypsin by enterokinase at the 26th week of gestation whereas lipase and colipase are secreted from the 24th week. The small intestine starts developing at the 10th week morphologically and functionally. At the same time when villi and crypts start to develop at the 11th to 12th week the first enzyme activities can be detected, i.e. sucrase-isomaltase, maltase-glucoamylase and lactase. Also peptidases and lysosomal hydrolases are measured at this age. With the exception of lactase, intestinal enzymes reach sufficient activities at the 25th week of gestation. Lactase activity remains low until the 32nd-34th week. For the digestion and absorption of lipids, protein and carbohydrates the gastrointestinal tract of premature infants under 1500 g in rather well equipped. Lipids are hydrolysed by the mutual action of breast milk lipase, lingual lipase, gastric lipase and pancreatic lipase. The carbohydrates lactose and oligosaccharides as supplements to breast milk are hydrolysed by lactase, sucrase isomaltase and maltase-glucoamylase. Breast milk proteins and cows milk hydrolysates are digested by pancreatic proteases into oligopeptides which can be hydrolysed within the lumen by brush border peptidases and be absorbed. Peptides also can actively be transported through the microvillus membrane and be hydrolyzed by intracellular peptidases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095635 TI - Interferon and butyrate treatment leads to a decreased sensitivity of NK target cells to lysis by homologous but not by heterologous effector cells. AB - Human K-562 and HHMS cells were pretreated with human recombinant interferon (IFN)-gamma and used as targets in NK assays against human and murine effector cells. A protective effect against NK lysis was observed only in the homologous assay, whereas no change or even a slight increase in NK sensitivity against heterologous effector cells was found. In cold target inhibition experiments IFN treatment of K-562 cells led to a decrease in their capacity to act as competitors in the homologous NK assay, leaving their inhibitory capacity unaltered in the heterologous assay. In accordance with results observed using human NK targets, murine YAC-1 cells treated with mouse recombinant IFN-gamma did not lose their susceptibility to human NK cells. However, they were markedly less susceptible to lysis mediated by murine effectors. Butyrate, another compound causing decreased sensitivity of K-562 cells for human natural killing, also failed to reduce the susceptibility against murine NK cells. The results indicate that the NK-resistant tumor target phenotype caused by IFN or differentiation inducing agents can only be detected by homologous but not by heterologous effector cells. This suggests that major differences exist between the inter- and intraspecies NK killing mechanisms. PMID- 3095636 TI - A genetic assay for the detection of aneuploidy in the germ-line cells of Drosophila melanogaster. AB - A 2-generation assay is described for the detection of aneuploidy in the germ line cells of Drosophila melanogaster. Larvae and adult females that carry marker mutations are exposed to test compounds, and the F2 generation is scored for exceptional phenotypes. As a consequence of nondisjunction and/or loss of the sex chromosomes, 5 exceptional phenotypes appear. These phenotypes are often indicative of specific types of nondisjunction. Based on the time course and the pattern of exception production of the treated parents, aneuploidy due to meiotic and mitotic defects can be separated. The genetic analysis of the exceptions reveals whether nondisjunction has occurred due to failure of the spindle fibres to disjoin chromosomes or attachment of the chromosomes. The described assay is an extension of the so-called Somatic Mutation and Recombination Test (SMART) and allows screening for different genetic endpoints: aneuploidy, recombinogenic and mutagenic activities in the same treatment. The effects of colchicine and EMS are described with respect to the induction of aneuploidy in the germ line and somatic mutation and recombination in the eyes, wings and female germ-line cells. Colchicine induces aneuploidy in the germ-line cells while the frequency of mosaic spots does not increase after colchicine treatment. This result suggests that aneuploidy plays little (if any) role in the formation of mosaic spots. Colchicine induces nondisjunction in the mitotically rather than in the meiotically dividing germ-line cells. EMS, as expected, induces high frequency of somatic mutation and recombination but not aneuploidy in the female germ line. PMID- 3095637 TI - Viability damage of Aspergillus flavus spores by an antifungal aerosol. PMID- 3095638 TI - Mitomycin-C is an unreliable inhibitor for study of DNA synthesis in Plasmodium. AB - Cytophotometric studies on DNA synthesis during asexual and sexual development of Plasmodium berghei contradicted earlier conclusions on DNA synthesis in Plasmodium which were largely based on experiments in which mitomycin-C had been used as a DNA replication inhibitor. Therefore, the effect of mitomycin on intra erythrocytic asexual development and on microgametogenesis, fertilization and zygote/ookinete development of P. berghei was studied in vitro. All DNA synthesizing stages (schizonts, exflagellating microgametocytes and zygotes) and also DNA synthesis itself in all such stages, are totally unaffected by mitomycin concentrations 10 times higher than that which inhibits normal development of the non-DNA-synthesizing rings and trophozoites. The results are explained by the mode of action of mitomycin. PMID- 3095639 TI - Aminotransferase activities in Trichomonas vaginalis. AB - A survey of aminotransferase activities present in a cell-free extract of the anaerobic protozoan, Trichomonas vaginalis was performed. 2-Oxoglutarate, oxaloacetate or phenylpyruvate acted as effective amino acceptors with tyrosine, phenylalanine, tryptophan, leucine, valine, isoleucine, aspartate, alanine, ornithine or lysine. Arginine, serine, glutamine, glycine, beta-alanine and gamma aminobutyrate were not active as amino donors. With pyruvate as acceptor, significant, yet low, activity was seen only with glutamate, lysine or phenylalanine. Partial purification of enzymes catalysing transamination of leucine, valine, isoleucine, alanine, ornithine and lysine were carried out. A single enzyme catalysed the transamination of ornithine and lysine. The substrate specificity of this enzyme is novel. A separate enzyme catalysed the transamination of all three branched chain amino acids. A third enzyme catalysed the alanine aminotransferase reaction. A fourth enzyme catalysing the transamination both of aromatic amino acids and aspartate has previously been purified [Lowe, P.N. and Rowe, A.F. (1985) Biochem. J. 232, 689-695]. PMID- 3095640 TI - Prospective payment for psychiatry--feasibility and impact. AB - Although 15 diagnosis-related groups (DRGs) have been proposed for psychiatric hospital patients, psychiatric hospitals are currently exempt from the DRG prospective payment system. We investigated the ability of the psychiatric DRGs to predict the hospital length of stay and costs by retrospectively analyzing the charts of 8816 randomly selected patients from 32 psychiatric hospitals throughout the United States. In addition, we developed other grouping systems to see whether they would have been better predictors of length of stay. We found that grouping the patients in the 15 psychiatric DRGs reduced the total variance in length of stay by only 3.9 percent. Furthermore, our best alternative grouping -based on major diagnostic categories, whether the patient was transferred from another facility, age, and psychiatric complications and comorbidities--reduced the variance by only 7.8 percent. We conclude that DRGs do not adequately predict length of stay or costs in psychiatric hospitals. We identified factors other than diagnosis that predicted the length of stay better, but all the models we tested would create large financial "winners" and "losers" and thus introduce inappropriate incentives into the care of patients in psychiatric hospitals. PMID- 3095641 TI - Single-dose therapy of gonococcal ophthalmia neonatorum with ceftriaxone. AB - We conducted a randomized clinical trial comparing a single intramuscular dose of 125 mg of ceftriaxone with a single intramuscular dose of 75 mg of kanamycin followed by topical gentamicin for seven days, and with a single intramuscular dose of 75 mg of kanamycin followed by topical tetracycline for seven days, in the treatment of gonococcal ophthalmia neonatorum in Nairobi, Kenya. Of 122 newborns with culture-proved gonococcal ophthalmia neonatorum, 105 returned for follow-up. Sixty-one infants (54 percent) received ceftriaxone, 32 received kanamycin plus topical gentamicin, and 29 received kanamycin plus topical tetracycline. Sixty-six (54 percent) of the Neisseria gonorrhoeae isolates were penicillinase producing. All 55 newborns who received ceftriaxone and returned for follow-up were clinically and microbiologically cured. One of 26 returning newborns who received kanamycin plus tetracycline and 2 of 24 returning newborns who received kanamycin plus gentamicin had persistent or recurrent gonococcal conjunctivitis. Ceftriaxone also eradicated oropharyngeal gonococcal infection in 18 newborns, whereas oropharyngeal infection persisted in 2 of 8 newborns who had received kanamycin (P not significant). We conclude that 125 mg of ceftriaxone as a single intramuscular dose is very effective therapy for gonococcal ophthalmia neonatorum, with marked efficacy against extraocular infection and without the need for concomitant topical antimicrobial therapy. PMID- 3095642 TI - Synovial-fluid beta 2-microglobulin levels in dialysis arthropathy. PMID- 3095643 TI - Aflatoxin-producing potential of Aspergillus flavus strains isolated from Spanish poultry feeds. AB - A total of 126 fungal strains belonging to the Aspergillus flavus group isolated from commercial poultry mixed feeds were studied. One hundred and twenty-five were identified as A. flavus and one as A. parasiticus. Forty nine strains (39%) produced aflatoxins on a crushed moist wheat medium (28 degrees C/10 days), whereas only sixteen (13%) showed specific fluorescence on Aflatoxin-Producing Ability Medium. In both media, mainly aflatoxins B1 and B2 were detected, the average concentration of aflatoxins being 4 294 +/- 1 083 micrograms/kg in crushed moist wheat medium, and 877 +/- 257 micrograms/kg in Aflatoxin-Producing Ability Medium. PMID- 3095644 TI - A toxic metabolite of Nigrospora oryzae (Berk and Br.) petch. AB - Nigrospora oryzae was isolated from dallisgrass (Paspalum dilatatum Poir.) collected in Auburn and from hay shipped under refrigeration to Florida. Some of these samples were eaten by cattle and horses that subsequently developed lameness. Metabolites of N. oryzae were separated by thin layer chromatography and tested for toxicity. Only one metabolite was toxic. Metabolite A showed toxicity to brine shrimp with an LD50 = 500 micrograms/ml in 8 h. It also had an antibiotic effect on Bacillus megaterium ATCC 14581 with a minimum inhibitory level of 10.1 micrograms/disc. As little as 435 micrograms of a crude methanolic extract of N. oryzae showed mild toxicity to chick embryos. The metabolite was not toxic to mice nor rats at the levels tested. Quantitative procedures developed for the determination of metabolite A showed that the maximum production occurred in yeast extract-sucrose liquid medium with an initial pH of 5-6, when incubated as a stationary culture for 28 days at 25 degrees C. It was concluded that metabolite A is a weak antibiotic rather than a mycotoxin, and was probably not associated with the symptoms of lameness observed in cattle and horses. The antibiotic is not one previously reported for N. oryzae. PMID- 3095645 TI - The occurrence of Aspergillus flavus in vegetative tissue of cotton plants and its relation to seed infection. AB - Twenty-seven mature cotton bolls with Aspergillus flavus Link colonies naturally occurring on the surface of the boll or lint were collected in the field in Arizona along with their subtending stems and peduncles. Bolls inoculated through the carpel wall 30 days after anthesis were allowed to mature in the field and were collected in the same manner. The seed and stem and peduncle sections of each boll were surface-sterilized, plated on agar media and observed for A. flavus. Seventy-eight percent of the naturally contaminated bolls with A. flavus in the seed also had the fungus in the stem and peduncle, whereas only 31% of the naturally contaminated bolls with no A. flavus in the seed had the fungus in the stem or peduncle. This difference was significant (P = 0.0125), indicating a positive relationship between seed infection and stem and peduncle infection. All of the bolls inoculated through the carpel wall had A. flavus in the seed, but only 11% of the stem and peduncle sections were infected, indicating that the fungus does not readily grow downward from the boll into the supporting stem or peduncle. This unidirectional pattern of movement (upward) was further substantiated in greenhouse experiments where cotton seedlings were inoculated at the cotyledonary leaf scar with A. flavus and plants were sequentially harvested, surface sterilized and plated. Aspergillus flavus was isolated from the cotyledonary leaf scar, flower buds, developing bolls, and stem sections in the upper portion of the plant. It was never isolated from roots or stem sections below the cotyledonary node, again indicating that the fungus does not readily move downward through the plant. PMID- 3095647 TI - Strategies for research on the interactions of drugs of abuse. PMID- 3095646 TI - Effects of antineoplastic agents on growth, morphology and metabolism of Torulopsis glabrata. AB - The effect of treatment by a number of antineoplastic agents on the growth, ultrastructure and macromolecular synthesis of T. glabrata was studied. Many differences were noted in the response of this yeast to these agents. Thiotepa and methotrexate inhibited the growth of T. glabrata, while it was resistant to endoxan-asta and vincristine sulphate. A variation of morphological response of T. glabrata was also observed. Methotrexate enhanced filamentation while thiotepa influenced the surface structures of the cells, resulting in loss of cytoplasmic materials and cell collapse. The other two drugs had little or no effect on the morphology of the yeast tested. The incorporation of precursors for macromolecular synthesis of T. glabrata in the presence of thiotepa and methotrexate was restricted. Thiotepa affected the uptake of precursors of RNA, DNA and protein limiting them to between 62 and 66% of the control values. In contrast, methotrexate limited the uptake of macromolecular precursors to a lesser extent. The possible mechanism of action of antineoplastic agents against yeast and the clinical implications of these findings are discussed. PMID- 3095648 TI - Interactions of cannabis with other drugs in man. AB - Only THC, of all cannabinoids, has a significant pharmacodynamic interaction with ethanol. Effects in man are additive as expected. THC, but not CBD, showed a similar interaction with barbiturates. Interactions with stimulants were weakly additive, but the former drugs do not reverse impairments from THC. Interactions between cannabinoids are controversial. Some evidence consistently suggests that CBD may block actions of THC, while other evidence could not show a clinically significant interaction. CBD did not alter the kinetics of THC, but it decreased metabolism of hexobarbital. Preliminary studies of interactions between THC and drugs affecting activity of neurotransmitters have not provided good tests of the mechanism of action of the drug, showing, at best, subtle effects of questionable clinical significance. The variable responses of subjects to THC is neither explained by differences in metabolism of drugs nor by differences in the setting in which the drug is taken. PMID- 3095649 TI - Alcohol and marijuana: concordance of use by men and women. PMID- 3095650 TI - Cocaine and other drug interactions: strategy considerations. PMID- 3095651 TI - Issues in the assessment of multiple drug use among drug treatment clients. PMID- 3095652 TI - Cigarette smoking: interactions with alcohol, opiates, and marijuana. PMID- 3095653 TI - Drug combinations in pleasure and pain. PMID- 3095654 TI - Drug interactions with methadone in humans. PMID- 3095655 TI - Statistical analysis of drug interactions. AB - The design of drug interaction experiments focusing on whether to characterize the interaction as addition, antagonism, synergism or potentiation is based, in part, on whether or not both substances when given alone affect the response. If both substances are active, one determines the potency of one substance relative to the other in affecting the response. This can be done for either quantitative or quantal data. Once the relative potency has been determined, subsequent studies involve combining fractional doses of the substances and comparing the results against those obtained using standard doses of the substances individually. Doses of the combination and the single substances are picked such that equivalent responses should be obtained if the effect of the two together is additive. The null hypothesis is that the two compounds behave as though they were different forms of the same substance, one of which is possibly (depending on the potency ratio) diluted with an inert substance. Equivalence of response can be tested using such parametric tests as Student's t or analysis of variance (or their nonparametric equivalents) for quantitative data. The chi-square or Fisher's exact probability test may be used for quantal data. Additivity is inferred if the null hypothesis is accepted. One infers either antagonism or synergism (depending upon the direction of the deviation from additivity) if the null hypothesis is rejected. If one substance is inactive when given alone the null hypothesis is that it has no effect when given with the other. This is tested using the same techniques as mentioned above, except that there is no need, obviously, to determine relative potency. The isobolographic method for studying drug interactions was compared with those mentioned above. Both approaches have the same conceptual basis. The isobolographic method is more tedious, however, since it entails determination of doses required to cause a specific response, whereas the other methods focus on the responses caused by specific doses. It was cautioned that, whatever the approach, it is the investigator's responsibility to know what assumptions are being made and to take all possible precautions before, during, and after the experiment to ensure that the reported results are meaningful. PMID- 3095656 TI - Critical factors in studying drug interactions. PMID- 3095657 TI - Problems of pharmacodynamic measurement related to psychoactive drug interactions in humans. PMID- 3095658 TI - Pharmacokinetic mechanisms of ethanol-psychotropic drug interactions. AB - Acute and chronic ethanol consumption alters psychotropic drug pharmacokinetics. An understanding of the processes of drug absorption, distribution, biotransformation, and elimination provide a rational basis for predicting and evaluating drug interactions. Careful application of clinical pharmacokinetic models describing these physiological processes are particularly appropriate for the task of understanding drug and alcohol interactions. Absorption: Acute alcohol inhibits first-pass effect increasing systemic bioavailability. Ethanol inhibits gastric emptying and may delay drug absorption (increase lag time of absorption) and decrease the rate of absorption. The effects of chronic alcohol intake are unknown. Distribution: Hypoalbuminemia may be present in alcoholics with liver disease. Fluctuations in free fractions of drugs may occur in the alcohol withdrawal period. The clinical effects of protein binding changes are dependent on degree of binding, hepatic extraction ratio, and binding protein. Acute low-dose ethanol increases hepatic blood flow while high doses decrease it. The effects of chronic alcohol intake on liver blood flow are unknown. Hepatic blood flow changes show the greatest effects on drugs with high extraction ratios. Metabolism: Acute alcohol ingestion usually inhibits drug metabolism and chronic intake (in the absence of severe liver disease) enhances metabolism. Cirrhosis impairs oxidative metabolism, but spares glucuronidation. Although these generalizations may serve as useful guidelines for predicting alcohol and psychotropic drug interactions, they should be applied with caution as exceptions do exist. PMID- 3095659 TI - Complex interactions between drugs and dietary factors. PMID- 3095660 TI - Transcripts of functionally rearranged gamma genes in primary T cells of adult immunocompetent mice. AB - The T-cell specific, rearranging gamma-chain genes bear striking resemblance to T cell receptor and immunoglobulin genes, but the role of gamma remains unknown. A central problem is to understand the conditions under which gamma RNA is expressed in cells. The transcription of gamma is abundant in T cells of fetal thymi, but is negligible in peripheral T cells of adults, suggesting that gamma is involved in development of the T-cell repertoire. However, gamma RNA was originally cloned from established lines of cytotoxic T cells (CTLs) derived from adult mice and this expression has been ascribed to non-physiological cell growth. Possibly consistent with this, most of the gamma RNA derives from genes rearranged abortively at the V gamma-J gamma junction of immunoglobulin genes, where V is the variable segment and J the joint segment. Here, we report the detailed analysis of gamma transcription in T cells of adult mice, and find that transcription may occur in T cells with a broad range of surface phenotypes; that it is predominantly of a single V gamma-C gamma unit (where C is the constant region); and that in cells freshly explanted from animals it can be of productively rearranged genes. PMID- 3095661 TI - A unique T-cell receptor complex expressed on human fetal lymphocytes displaying natural-killer-like activity. AB - We have recently derived a series of cloned cell lines displaying natural killer (NK) cell-like activity from normal human fetal blood (25 weeks). The lines were obtained after repeated stimulation of mononuclear cells with allogeneic Epstein Barr virus (EBV)-transformed B lymphocytes and are interleukin-2 (IL-2) dependent. Initial characterization of the clones has been reported previously. Certain of these clones have been found to have unusual surface characteristics, namely, they are recognized by several well-defined anti-T3 antibodies, but do not react with WT31, which is thought to recognise an invariant epitope of the human (Ti-alpha beta) structure. Transcription of the genes encoding the alpha- and beta-chains of the T-cell receptor was assessed in two of these clones (F6A4 and F6C7). Ti-beta genes were found to be expressed, whereas alpha messenger RNA was not detected in Northern blot analysis. These data strongly suggest that these cells do not produce a stoichiometric T3/Ti-alpha beta receptor complex. However, experiments performed with a monoclonal antibody (anti-NKFi) developed against F6C7 cells demonstrated the existence of a unique clonotypic structure [relative molecular mass (Mr) 85,000 (85K)] which is surface-associated with T3 proteins. Furthermore, both anti-T3 and anti-NKFi were found to block cytotoxic effector function. Together, the results support the view that T3 proteins are involved in non-major histocompatibility complex (MHC)-restricted cytotoxic reactions mediated by certain circulating fetal lymphocytes which are likely to use a clonotypic structure distinct from both the 'first' (alpha beta) and the putative 'second' (gamma delta) T-cell receptor to recognize their target. The present studies were designed to characterize this structure. PMID- 3095662 TI - A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. AB - Immunoglobulin gene promoters are active only in lymphoid cells and this tissue specific activity requires an octamer sequence, ATTTGCAT. Paradoxically, this same octamer motif seems to be a transcriptional control element in promoters which are active in all tissues. Using an electrophoretic mobility shift assay to identify DNA binding proteins, we have now detected two species of nuclear proteins which bind specifically to this octamer. One previously characterized form (NF-A1) was found in all cell lines tested while the other form (NF-A2) was restricted to lymphoid cell lines. NF-A2 was found in cell lines representing all stages of B-cell differentiation and in half of the T-lymphoma cell lines tested. The identification of a lymphoid-specific octamer binding protein may account for the lymphoid-specific activity of immunoglobulin promoters. PMID- 3095663 TI - Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. AB - Formation of syncytia, with progression to cell death, is a characteristic feature of in vitro cultures of susceptible cells infected with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). Viral antigen-positive multinucleated giant cells have also been observed in histological sections from infected individuals. In vitro, formation of these multinucleated giant cells occurs through cell fusion which is dependent on cell surface expression of the differentiation antigen CD4. Utilizing a recombinant vaccinia virus containing the gene for the envelope glycoprotein of HTLV-III/LAV, we demonstrate that cell-surface expression of this protein, in the absence of other HTLV-III/LAV structural or regulatory proteins, is sufficient to induce CD4 dependent cell fusion, leading to cell death, one of the characteristic manifestations of AIDS (acquired immune deficiency syndrome) virus cytopathology. This process may contribute to the loss of CD4+ T cells seen in AIDS. PMID- 3095664 TI - Sequence, structure, receptor-binding domains and internal repeats of human apolipoprotein B-100. AB - Apolipoprotein (apo) B-100, the major protein component in low density lipoprotein (LDL), is the ligand that binds to the LDL receptor. It is important in the metabolism of LDL and elevated plasma levels of LDL-apo B are strongly associated with increased risk of coronary artery disease. Although apo B-100 is of great clinical and biological importance its primary structure has defied chemical elucidation, mainly because of its enormous size, insolubility, and tendency to aggregate. Less than 5% of the apo B-100 sequence has been reported, despite the efforts of many laboratories over the past twenty years. Here we report the complete amino acid sequence of human apo B-100 as deducted by sequence analysis of complementary DNA clones; 2,366 of the 4,536 residues were also confirmed by direct sequencing of apo B-100 tryptic peptides. The distribution of trypsin-accessible and -inaccessible peptides of the protein on LDL is non-random and they can be grouped into 5 hypothetical domains. Of 20 potential N-glycosylation sites identified in the sequence, 13 were found by direct peptide sequencing to be glycosylated, and 4 unglycosylated. Examination of the primary structure of apo B-100 reveals that it contains a large number of long (greater than 70 residues) internal repeats and an even larger number of shorter ones, suggesting that the apo B-100 sequence was derived largely from internal duplications. Finally, using synthetic peptides of a specific region of apo B-100, we have identified a potential LDL receptor-binding domain (residues 3,345-3,381) which can bind to the LDL receptor and suppress 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase activities in cultured human fibroblasts. PMID- 3095665 TI - Interactions of N-CAM with heparin-like molecules. PMID- 3095667 TI - [Determination of the urinary albumin excretion in the early case-finding of nephropathy in patients with diabetes mellitus]. PMID- 3095666 TI - [Total hip prosthesis, indications, results, longevity]. PMID- 3095668 TI - [Current insights in factor VIII biology]. PMID- 3095669 TI - [Presynaptic mechanisms of the change in segmental responses accompanying the formation of the spinal locomotor generator in the cat]. AB - It is shown on unanesthetized immobilized decorticated cats that spinalization of the animal leads to depolarization of the central afferent terminals, decrease of early polysynaptic responses in motoneurons and dorsal root potentials (DRP) evoked by stimulation of the low-threshold cutaneous and muscle afferents, increase of early polysynaptic responses and DRP evoked by stimulation of high threshold muscle afferents, reduction in the activity of intermediate nucleus interneurons mono- and polysynaptically connected with primary afferents, rise of the activity of interneurons di- and oligosynaptically connected with primary afferents. Injection of DOPA into spinal animals leads to opposite changes. Dependence between changes in the state of segmental neuronal apparatus and the level of spinal locomotor generator activity are discussed on the basis of the data obtained. PMID- 3095670 TI - [Effector mechanisms of graft rejection]. AB - The rejection of an allograft is a complex phenomenon involving various subsets of immune cells. If the role of humoral immunity and cytotoxic T cells is well demonstrated, helper T cells have also a major effect in some models of allograft destruction. Moreover, Natural Killer cells, Killer cells, monocytes/macrophages, B lymphocytes are also implicated in various stages of graft rejection. The analysis of the clonal repertoire of T lymphocytes, the discovery of the structure and function of the T-cell receptor and finally the genetic control by encoded genes of the immune response may lead to a better comprehensive and therapeutic approach of graft rejection. PMID- 3095671 TI - Recognition of an allograft. AB - The recognition of a tissue allograft as foreign and the induction of an immune response against that graft is poorly understood, but is obviously extremely complex and is influenced by a number of factors. MHC: Incompatibility for the MHC of the donor is obviously important, and incompatibility for both Class I (eg. HLA-A, B) or Class II (eg. HLA-DR) antigens will induce the response. However in some circumstances presentation of Class I antigen only on viable cells will induce suppression rather than a response leading to rejection. Presentation of histocompatibility antigens: Two theoretical methods exist by which the host may recognise foreign alloantigen. In the first host antigen presenting cells present alloantigen in association with host Ia to host TH (the conventional form of antigen presentation), while in the second passenger leucocytes (dendritic cells) in the donor allograft present incompatible Ia (Class II) antigen directly to host TH cells, or indeed if Ia is identical with the host they may present Class I antigen to host TH cells. There is considerable experimental evidence which suggests an important role for the passenger leucocyte in the induction of the allograft response. Minor histocompatibility antigens: Not a great deal is known about these systems in man, but there are no doubt very many. From our knowledge of the behaviour of skin and cardiac allografts in the mouse transplanted across major and minor barriers, minor antigens may induce an immune response to an allograft especially in the presence of compatibility for the MHC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095672 TI - [Suspected pyruvate carboxylase deficiency in 4 children with Leigh disease]. AB - Clinical observations and results of investigations of pyruvic acid metabolism are reported in 4 children in whom subacute necrotizing encephalomyelopathy of Leigh was diagnosed intravitally. Attention is called to the similarity of the clinical manifestations with its onset in the first year of life, deficient body weight and growth, progressing neurological disturbances (weakening of muscle power, tremor, ataxia, nystagmus), course with periods of exacerbations, tachypnoea, skin changes (hirsutism, telangiectasia, perspiration), death at the age of 2-3 years. The biochemical changes in all children included raised serum levels of lactic acid, pyruvic acid and alanine, and acid-base equilibrium disturbances with metabolic acidosis (relatively balanced respiratory alkalosis). The results of the test of intravenous loading with glucose and alanine carried out in all children indicated indirectly reduced activity of pyruvate carboxylase. In one child histological examination of the brain carried out postmortem confirmed the diagnosis of Leigh's disease. PMID- 3095673 TI - [A case of ossified yellow ligaments (ossified ligamenta flava) of the thoraco lumbar region and magnetic resonance imaging]. AB - A Case of ossified yellow ligaments in thoraco-lumbar region is reported. A 47 year-old-male complained low back pain with suddenness in August, 1984. One month later, he noticed dyesthesia on his right lower extremity and gait disturbance. These symptoms progressed slowly. In June, 1985, he admitted to The Jikei University Hospital. On neurological examinations, he was noticed an intermittent claudication, spastic paraparesis and stocking type sensory loss in his lower extremities. Plain lumbar X-ray films showed ossified yellow ligaments (OYL) in the posterior half of the spinal canal from the level of 10th thoracic to second lumbar vertebrae. Magnetic resonance imaging disclosed marked indentations of the spinal cord at the same level. The wide laminectomy was carried out and OYL were removed totally in gentle manner. Postoperative course was uneventful. His sensory disorders improved remarkably and he gained good muscle strength in his lower extremities, but a considerable spasticity remained still. OYL is closely related to the developmental canal stenosis, the spondylosis and the other degenerative disorders such as ossification of posterior longitudinal ligaments. This allows more complicated neurological signs and symptoms in the case of OYL. When OYL is suggested, it is recommended to performed whole spinal radiological survey. The surgical consideration should be done. From this point of view, MRI would be a most useful weapon. PMID- 3095674 TI - The effect of inhibiting Schwann cell mitosis on the re-innervation of acellular autografts in the peripheral nervous system of the mouse. AB - Reactive gliosis in the zone immediately proximal to transection of the sciatic nerve has been inhibited by intraneural injection of mitomycin C, an anti-mitotic agent known to arrest Schwann cell division after transection, crush or demyelination. Mitomycin C-pretreated proximal stumps were subsequently sutured to cellular or acellular autografts (0.5 cm long) and neurite growth into and within the grafts was examined during a 5-week post-operative period. Neurites grew into cellular autografts and became associated with the resident population of Schwann cells within the grafts, to the extent that remyelination was well established in the majority of Schwann cell basal lamina tubes by week 5 post suture. In marked contrast, very few neurites grew into acellular grafts during this time, and where axons and Schwann cells were seen they tended to be grouped in 'minifascicles'. The results suggest that neurite outgrowth from proximal stumps is dependent upon active Schwann cell participation. PMID- 3095675 TI - Effect of hypercapnia and/or hypoxemia and metabolic acidosis on kinetics and concentrations of phenytoin in the cerebrospinal fluid of conscious rabbits. AB - The present study was designed to determine the effect of changes in gases and pH in the blood on kinetics and passage to the cerebrospinal fluid (CSF) of phenytoin (DPH). Five groups of 6 rabbits were used, a control [with a mean partial pressure (Pa) of oxygen of 84 +/- 2 (SEM) mmHg, partial pressure of carbon dioxide (PaCO2) of 23 +/- 1 mmHg and pH = 7.512 +/- 0.018], a second group with hypercapnia (PaCO2 = 65 +/- 3 mmHg, pH = 7.244 +/- 0.008), a third group with hypoxemia (PaO2 = 48 +/- 2 mmHg), a fourth group with hypercapnia combined with hypoxemia (PaCO2 = 72 +/- 3 mmHg, PaO2 = 51 +/- 1 mmHg and pH = 7.252 +/- 0.008) and a fifth group with metabolic acidosis (pH = 7.232 +/- 0.011). All animals were conscious during the experiments following the administration of 10 mg/kg (i.v.) of phenytoin, hypoxemia decreased the clearance of phenytoin from 4.20 +/- 0.55 to 2.65 +/- 0.44 ml/min per kg (P less than 0.05) and consequently the area under the plasma concentration/time curve (AUC) for phenytoin increased (2575 +/- 319 to 4316 +/- 740 micrograms min/ml; P less than 0.05). Metabolic acidosis increased the volume of distribution of phenytoin from 780 +/- 70 to 1103 +/- 65 ml/kg (P less than 0.01). The protein binding of phenytoin was not affected by any of the experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095676 TI - The binding of 3H-(3-MeHis2) thyrotropin releasing hormone to brain membranes and temperature response to thyrotropin releasing hormone in different strains of mice. AB - The effect of thyrotropin releasing hormone (TRH) on the colonic temperature of five strains of mice, namely, Swiss Webster, ICR, C57 BL, BALB and DBA, was determined. Intraperitoneal injection of TRH induced an hyperthermic response, the magnitude of which differed in different strains of mice. Peak effect was observed 15 min after the injection and the effect lasted for about an hour depending upon the dose. TRH produced a dose related hyperthermia in DBA mice, whereas in other strains an inverted U-shaped curve was obtained, with maximal response at 20 mg/kg and declining at 40 mg/kg dose. 3H-(3-Mehis2) TRH bound specifically to brain membranes at a single high affinity site with a B max of 53.72 fmol/mg protein, and Kd of 3.77 nM (for swiss Webster mice). The Kd and B max values did not differ for any strain. It is concluded that the nature of TRH induced changes in colonic temperature depends both on the dose and the strain of mice, and that factors other than the brain receptors for TRH may be responsible for its variable hyperthermic effect. PMID- 3095677 TI - A relationship between gonadotropins and visuospatial function. AB - Follicle Stimulating Hormone (FSH) levels were negatively correlated with visuospatial function in two successive testing sessions in 32 young adult men. Men with high concentrations of FSH performed poorly on three-dimensional tests and tests of point localization. Men with low concentrations tended to perform better. Luteinizing Hormone (LH) tended to correlate positively with verbal/sequential skills and with two of the visuospatial skills for one session; testosterone was positively correlated with one spatial test. Multiple regression between the average performance on visuospatial tests and the three hormones produced Rs of 0.67 and 0.60, accounting for 39% and 29% of the variance, respectively, in Sessions 1 and 2. In women, the hormonal/behavior relationships were less clear although in many ways similar. For example, FSH was negatively correlated with one visuospatial test but only after the effects of estradiol and progesterone were partialled out. FSH was positively correlated with word fluency as was LH. With respect to sex differences women were poorer than men on the visuospatial tests and better on verbal fluency which is consistent with women's generally higher FSH levels and the negative relationship between FSH and visuospatial skills and the positive relationship with fluency. PMID- 3095678 TI - Quantification of the dopamine innervation in adult rat neostriatum. AB - Conditions leading to specific and integral visualization of dopamine axon terminals (varicosities) were tested in adult rat cerebral hemisphere slices incubated with [3H]dopamine and processed for high resolution radioautography. Specific visualization of the dopamine endings was achieved after incubation with 10(-6) M [3H]dopamine in the presence of a monoamine oxidase inhibitor (pargyline 10(-4) M), and of desipramine (5 X 10(-6) M), an inhibitor of catecholamine uptake by noradrenaline and serotonin neurons. [3H]Dopamine varicosity labeling was eliminated by the addition of 5 X 10(-5) M benztropine (an inhibitor of catecholamine uptake by catecholamine neurons), and was almost absent when dopamine nerve cell bodies of the midbrain had been previously destroyed with 6 hydroxydopamine. In dopamine-denervated neostriatum incubated without desipramine, a second set of labeled terminals was also visible. These were identified as serotoninergic, since their labeling was suppressed by citalopram, an inhibitor of monoamine uptake highly specific for serotonin neurons. There was no desipramine-sensitive but citalopram-resistant varicosity labeling suggestive of neostriatal noradrenaline innervation. In normal striatum, incubation at 35 degrees C always resulted in a labeling of dopamine varicosities restricted to a narrow band which followed the contours and cut surface of this anatomical region. This unusual distribution was the result of an uptake barrier generated by the tightly packed dopamine varicosities. Indeed, the striatal dopamine varicosity labeling was more widespread after partial 6-hydroxydopamine denervation or in normal tissue incubated either with a higher [3H]dopamine concentration (5 X 10(-6) M), in the presence of relatively low benztropine concentrations (10(-5) M), or at lower temperature (15 degrees C). Material incubated at 15 degrees C for 90 min was suitable for purposes of quantification: labeled varicosities were then visualized throughout the striatum and across the full thickness of the slices; moreover, the number of labeled varicosities plotted against radioautographic exposure time increased in parallel and reached a plateau at the same time in neostriatal sectors with widely different innervation densities. At a rostral transverse level across neostriatum, the dorsolateral quadrant showed hyperdense "patches" of labeled terminals distinguishable from an already dense surrounding "matrix", whereas, ventromedially, the dopamine innervation appeared more uniform and somewhat less dense.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3095679 TI - Critical development periods for inhibition of ornithine decarboxylase by alpha difluoromethylornithine: effects on ontogeny of sensorimotor behavior. AB - The roles of ornithine decarboxylase and the polyamines in behavioral development were examined through the use of alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase. alpha-Difluoromethylornithine was administered either prenatally during gestation (days 15-17) or postnatally (days 1-20) to examine critical periods of sensitivity. Prenatal alpha difluoromethylornithine administration resulted in a deficit in early sensorimotor ontogeny: latencies in surface righting reflex (postnatal days 1-5) and negative geotaxis (postnatal days 5-8) were prolonged, and time spent pivoting (postnatal days 7, 9, and 11) was reduced. In contrast, postnatal alpha difluoromethylornithine primarily influenced later maturing, complex integrative behaviors such as swimming and open field activity. Thus, the behavioral effects of alpha-difluoromethylornithine exposure are highly dependent upon the age at which the drug is administered, a finding in keeping with the participation of the ornithine decarboxylase/polyamine system in cell replication and differentiation during discrete periods of neural development. The behavioral consequences of ornithine decarboxylase inhibition during these critical periods are thus related primarily both to the timetable for cellular maturation in each brain region. PMID- 3095680 TI - Case for diagnosis. AIDS. PMID- 3095681 TI - The cochlear implant program. PMID- 3095682 TI - Community adjustment among the elderly: psychopharmacological patterns and diagnoses. PMID- 3095683 TI - Evaluation of a bacteriological screening method for drinking water control on board ships. PMID- 3095684 TI - Post-traumatic stress disorder in the older veteran. PMID- 3095685 TI - Medical Officer Training Corps: Indiana's success story. PMID- 3095686 TI - Early experiential environment, maternal bonding and the susceptibility to post traumatic stress disorder. PMID- 3095687 TI - Neubruecke (a new bridge) in the Army Reserve medical training network. PMID- 3095688 TI - Hypothalamic pituitary function in severely head injured Vietnam veterans. PMID- 3095689 TI - Pill induced esophageal ulceration and stricture following cardiac surgery. PMID- 3095690 TI - Illness in American military men in Egypt. PMID- 3095691 TI - Reiter's disease complicated by ulcerative colitis: a case report. PMID- 3095692 TI - Case for diagnosis: leiomyoma with carneous degeneration. PMID- 3095694 TI - Toxic shock and a gunshot wound. PMID- 3095693 TI - Transsphenoidal hypophysectomy meningitis. PMID- 3095695 TI - Does the United States Army need a sports award? PMID- 3095696 TI - A case for the military pediatrician. PMID- 3095697 TI - Case for diagnosis. AIDS. PMID- 3095698 TI - Potential of influenza vaccine and amantadine to prevent influenza A illness in Canadian forces personnel 1980-1983. PMID- 3095699 TI - Patient referrals and consultations initiated by Pacific Fleet ships during in port periods. PMID- 3095700 TI - Temporary paternal absence and health care utilization: a cohort-controlled study. PMID- 3095701 TI - Cardiovascular risk modification: a multidisciplinary approach in a USAF clinic setting. PMID- 3095702 TI - Evaluation of new plastic envelope microbiology (PEM) methods as adjuncts in the diagnosis of Candida albicans and Trichomonas vaginalis vaginitis. PMID- 3095703 TI - Amebic liver abscess: the unconsidered and undiagnosed mimic. PMID- 3095704 TI - Gallstone ileus: recent experience at Brooke Army Medical Center. PMID- 3095705 TI - Hepatobiliary kinetics after whole body irradiation. PMID- 3095706 TI - Urinary stress incontinence following radical vulvectomy: a report of two cases. PMID- 3095707 TI - Synchronous ectopic pregnancy and appendicitis. PMID- 3095708 TI - Salpingitis isthmica nodosa: radiographic hallmarks and clinical significance. PMID- 3095709 TI - Primary carcinoid tumor of the testis. PMID- 3095710 TI - Death associated with aspirin overdose. PMID- 3095711 TI - Evidence for separate receptors that mediate parallel effects of serotonin and small cardioactive peptideB (SCPB) on adenylate cyclase in Aplysia californica. AB - Recent evidence suggests that serotonin (5-HT) and a neuropeptide, small cardioactive peptideB (SCPB), exert parallel modulatory actions on neuronal and muscular function in Aplysia via changes in the levels of cAMP. We have examined the effects of both of these neurotransmitters on the adenylate cyclase activity in membrane homogenates of pleural ganglia. The results indicated that 5-HT and SCPB enhance the production of cAMP via a direct activation of adenylate cyclase. In addition, we found that the increase in cyclase activity produced by 5-HT could be selectively blocked by the S2-serotonergic antagonists, ketanserin and ritanserin. Thus, specific 5-HT receptors are present which appear to be distinct from those that mediate the effects of SCPB on the activity of adenylate cyclase. PMID- 3095712 TI - L-deprenyl attenuates stress ulcer formation in rats. AB - Both intraperitoneal and intracerebroventricular (i.c.v.) administration of the monoamine oxidase-B inhibitor L-deprenyl markedly attenuated restraint stress induced gastric ulcers in rats. L-Deprenyl given i.c.v. attenuated stress ulcers in microgram doses and virtually abolished ulcer formation at a dose of 2.0 micrograms. These data suggest that intact or augmented central dopaminergic function may be an essential component of gastric mucosal protection. PMID- 3095713 TI - Two types of electrocortical paroxysms in an inbred strain of rats. AB - In 10 subjects of a particular inbred strain of rats (WAG/Rij), two types of spike-wave complexes were detected in the cortical electroencephalogram (EEG) during the two recording hours. The first type, already well-known, occurred in 8 of the 10 rats. This type was seen both during sleep and wakefulness and was accompanied by behavioural concomitants, reminiscent of human petit-mal epilepsy. A mean of 18 discharges/h was found. The second type, a novel one with a differential shape, occurred in 7 rats with a mean number of 14 discharges/h. In contrast to the first one, this spike-wave complex was not accompanied by behavioural correlates and was almost exclusively present during wakefulness. Four reasons make this strain of rats attractive as an additional animal model for epileptogenic activity: the occurrence of two types of spike-wave complexes, the high percentage of animals showing these phenomena, the genetic constitution of these rats and the fact that they are commercially available. PMID- 3095714 TI - Comorbidity and length of stay: a case study. PMID- 3095716 TI - Teaching your patient about his Hickman catheter. PMID- 3095715 TI - The effect of arcuate nucleus transplantation on the development of the anterior pituitary in monosodium glutamate-treated rats. AB - Treatment with monosodium glutamate (MSG) during the neonatal period is known to produce a selective lesion of the arcuate nucleus in rat brain, which is the major site of production of growth hormone releasing-hormone (GRH), followed by a secondary reduction in growth hormone (GH) synthesis in the anterior pituitary. Normal arcuate nuclei from hypothalamic areas of newborn rats were transplanted into the third ventricles of 27-day-old rats which were treated with MSG on alternate days for the first 10 days of life. Ninety days after birth, the anterior pituitaries were examined for GH synthesis by immunohistochemical staining with GH antiserum. The results indicated that the impaired GH synthesis in the anterior pituitary treated with MSG was partially restored in some recipients by grafts of arcuate nuclei in which the GRH-containing neurons were clearly detected by immunohistochemical staining with GRH antiserum. PMID- 3095717 TI - The role of glucose, insulin and glucagon in the regulation of food intake and body weight. AB - Glucose and related pancreatic hormones play a major role in the metabolism of monogastric mammals yet their influence on hunger and/or satiety is, as yet, poorly understood. Glucose, insulin and glucagon rise during a meal and gradually decline to baseline levels shortly after a meal. A sudden drop in plasma glucose as well as insulin have been reported just prior to the onset of a meal but the functional significance of this is not yet clear. Systemic injections of glucose have no acute satiety effects but intraduodenal and intrahepatic infusions reduce food intake and free-feeding and deprived animals respectively. Treatments which decrease cellular glucose utilization directly (2-DG) or indirectly (insulin) increase food intake while exogenous glucagon (which produces hyperglycemia) decreases it. There is considerable evidence that some or all of these effects may be due to a direct central action of glucose, 2-DG, insulin, and glucagon on brain mechanisms concerned with the regulation of hunger and satiety although influences on peripheral "glucoreceptors" have been demonstrated as well. The functional significance of glucoprivic feeding is, however, questioned. The feeding response to 2-DG and related compounds is capricious, and its temporal course does not parallel the hyperglycemic reaction which presumably reflects cellular glucopenia. Moreover, numerous brain lesions which increase, decrease, or have no effect on ad lib intake and often have no effect on the response to deprivation have been shown to severely impair or abolish feeding responses to systemic injections of 2-DG that produce severe central as well as peripheral glucopenia. Feeding responses to insulin are intact after most of these lesions, suggesting that this hormone may influence food intake in a fundamentally different fashion. The mechanism of insulin action is not understood--the classic feeding response is obtained only with doses that are pharmacological when compared to normal plasma levels and there is increasing evidence that lower doses may have opposite, inhibitory effects on food intake and body weight. Relatively small doses of glucagon decrease food intake (although opposite facilitatory effects have been reported after even smaller doses) but the effect does not appear to be due to hepatic mobilization of glucose as initially assumed. Decreases in food intake after intracranial injections of very small doses suggest a direct central action. PMID- 3095718 TI - Restraint stress in biomedical research: a review. AB - The use of restraint or immobilization for investigations of animal physiology, pathology and pharmacology has an extensive history. The major use of this technique has been as a "stressor" for the induction of stress response syndromes in animals. Many such syndromes have been characterized from the behavioral level to the neurochemical concomitants of stress. As a consequence of this particular use of the restraint procedure, much information concerning drug effects on stress response syndromes has been obtained. Indeed, many researchers in the area of gastrointestinal drugs routinely screen their new compounds in a restraint model of gastric stress ulcer. The purpose of this review is to present for researchers, a summary of the methods for, the parameters of, and known drug effects on, restraint-induced pathology. In our experience, this technique has proven to be a very useful one for the examination of both central and peripheral mechanisms of stress-related disorders, as well as for studying drug effects upon these disorders. PMID- 3095719 TI - Dependency levels of elderly people in institutional care in Canterbury. AB - All elderly persons in long term or social relief institutional care in the Canterbury area were assessed using a rating scale which assessed self care, continence, orientation and social integration. There was no difference in dependency in residents in homes provided by religious and welfare organisations compared with residents in homes provided by the private sector. Organisations providing a comprehensive service with flats, residential and hospital sections had lower dependency residents in the residential care section than institutions that provide home care alone. Public hospital long stay patients were significantly more dependent than private sector long stay patients. Of all subjects in residential homes and long term hospitals in Canterbury 49.3% were essentially independent in the dimensions assessed. This study adds further data concerning patterns of dependency of elderly subjects in institutional care. PMID- 3095720 TI - Evaluation of three methods of platelet labelling. AB - The study of the kinetics of labelled platelets makes sense only when the platelets preserve their viability after separation and labelling. The separation and labelling procedures described in the manual of two producers of 111In oxinate (Amersham, Mallinckrodt) have been evaluated by in vitro aggregation tests. The method of Mallinckrodt diminished the aggregation capacities of the thrombocytes. The labelled platelets with normal in vitro aggregation response (Amersham) were tested in vivo in 11 patients who underwent peripheral bypass surgery. The platelet half-life and the platelet accumulation on bypass grafts were checked one week post-operatively. Because of the poor in vivo response of both methods (exponential half-life curve and bad graft visualization), a third method was optimized in our laboratory with good in vitro and in vivo results in 12 patients. PMID- 3095721 TI - Monoclonal antibody hapten radiopharmaceutical delivery. AB - One hundred micrograms of monoclonal antibody (MoAb) CHA255 with a binding constant Kb of 4 X 10(9) was complexed with indium-111 labelled BLEDTA II, BLEDTA IV, benzyl EDTA, and an EDTA conjugate of Fab. The 24-h tumour and organ distribution of BALB/c mice bearing KHJJ tumours was studied for each compound alone, the antibody complex, and 3 h following a chelate chase of the antibody complex. Whole body biological half-life was measured for 7 days with and without a chelate chase for each antibody complex. The 24-h whole body counts dropped 20 to 60% and blood concentration fell over 89% within 3 h of administering the chelate chase. Theoretical equivalent human organ doses were calculated from the 24-h organ concentrations, effective half-life, and MIRD 11 S values (absorbed dose per cumulated activity). Liver and spleen were the target organs, with the dose ranging from 0.50 to 3.91 rads mCi-1. The reduction in organ radiation dose varied up to 95% following the chelate chase. Rapid selective renal clearance of chelate labelled radiopharmaceuticals by competitive inhibition (chelate chase) of their reversible binding to monoclonal antibodies enhances tumour imaging and improves the radiation dosimetry. PMID- 3095722 TI - [New generation of synthetic resins--dental adhesives. Composition--properties- clinical use]. PMID- 3095723 TI - [Oral streptococci]. PMID- 3095724 TI - [Gingival cyst in an adult: report of a case]. PMID- 3095725 TI - [Radiopacity of composite restorative materials]. PMID- 3095726 TI - [The retention of pins]. PMID- 3095727 TI - [Radiologic studies of the tooth bud of permanent teeth whose primary predecessors showed periapical inflammation]. PMID- 3095728 TI - [Injection-molded thermoplasticized gutta-percha technics for root canal filling (report of clinical cases)]. PMID- 3095729 TI - [Untoward effects of orthodontic treatment]. PMID- 3095730 TI - [Radiation as an etiologic factor in tumors of the head and neck]. PMID- 3095731 TI - [Management of avulsed anterior permanent teeth]. PMID- 3095732 TI - [Case 5: Tumor of the upper gingivo-labial fold]. PMID- 3095733 TI - [Craniofacial sutures]. PMID- 3095734 TI - [Physiology of the dento-gingival junction. New concepts]. PMID- 3095735 TI - [Temporomandibular joint dysfunction in children. Etiologic factors and clinical features]. PMID- 3095736 TI - [Uses of micromechanical interlocking in fixed prosthetics]. PMID- 3095737 TI - [The effect of fillings with overhangs on periodontal status]. PMID- 3095738 TI - [In vitro study of the inhibition of dental resin polymerization by atmospheric oxygen]. PMID- 3095739 TI - [Squamous cell carcinoma of the lip. I. Epidemiology, etiology, clinical and histological aspects]. PMID- 3095740 TI - [The biologically appropriate time to start orthodontic treatment]. PMID- 3095741 TI - [Prosthetic silicones (polyvinylsiloxanes). New elastomeric impression materials]. PMID- 3095742 TI - [Swelling in the cheek. Initial clinical sign of pulmonary tuberculosis]. PMID- 3095743 TI - [In vitro study of whether the residual monomer is washed away and to what extent in the thermal polymerization of acrylic resins]. PMID- 3095745 TI - [A supernumerary tooth and an impacted cuspid]. PMID- 3095744 TI - [An in vitro study of 4 photo-polymerized opaque synthetic resins]. PMID- 3095746 TI - [Supernumerary 4th molar]. PMID- 3095747 TI - [Developmental anomaly of the condyle and coronoid process]. PMID- 3095748 TI - [Comparative study of the prevalence of dental caries in a school age population and the fluoride content of the drinking water in the prefecture of Larisa]. PMID- 3095749 TI - [Restoration of cervical erosions and abrasions]. PMID- 3095750 TI - [Squamous cell carcinoma of the lower lip. II. Diagnosis and surgical treatment]. PMID- 3095751 TI - [The angle of flexure in patients with increased lower anterior facial height]. PMID- 3095752 TI - [Problems during the eruption of the permanent 1st molars]. PMID- 3095753 TI - [Compound odontomas (report of 2 cases)]. PMID- 3095755 TI - [The effect of the moisture and temperature on the retentive ability of cements]. PMID- 3095754 TI - [Comparative in vitro study of visible light-cured and chemically-cured sealants]. PMID- 3095756 TI - [Endodontic implants. Clinical application of techniques]. PMID- 3095757 TI - [The management of a case of fused central incisors in the maxilla]. PMID- 3095758 TI - Nursing the family in extended care settings. PMID- 3095760 TI - The term "quality". PMID- 3095759 TI - Replication of scrapie prions in hamster eyes precedes retinal degeneration. AB - Progressive degeneration of outer retinal structures occurs in hamsters with scrapie. In order to determine the relationship between histopathologic changes and replication of the scrapie agent, hamsters were inoculated intracerebrally with approximately 10(7) ID50 units. Animals sacrificed at 50 days after inoculation showed no signs of neurologic dysfunction, but had high titers of the scrapie agent or prions in both neural and nonneural portions of the eye. Prion titers in retina were greater than 10(7) ID50 units/ml of 10% (w/v) homogenate and equal to those found in optic nerve and brain. No histopathologic changes were seen by light microscopy in any ocular structure. At 70 days after inoculation, neurologic dysfunction was profound. The titers of the scrapie agent in brain, lens, retinal pigment epithelium, cornea, retina, and optic nerve were not significantly changed compared to those found at 50 days; however, retinal degeneration was severe. No morphologic changes were observed in cornea, pigment epithelium or optic nerve. These findings show that scrapie prion replication to maximal levels precedes the onset of degenerative changes in retina. Furthermore, the retina is preferentially susceptible to the degeneration induced by the scrapie agent while the other ocular structures containing significant levels of prions seem to escape injury. PMID- 3095761 TI - The Adverse Patient Occurrences Inventory: validity, reliability, and implications. AB - The Adverse Patient Occurrences (APO) Inventory, a quality of care screening instrument, was tested for validity and reliability. A positive relationship was found between the relative proportion of adverse events experienced by patients with diagnoses in two diagnosis-related groups and their hospital costs and lengths of stay. As hospitals strive to provide efficient care, they will require measures such as the APO instrument to assess the quality of care they give. Such information can also help hospitals meet regulatory agencies' requirements. PMID- 3095762 TI - Computerizing the medical staff office. AB - To assist its medical staff in making appointments and reappointments to the medical staff, delineating clinical privileges, and maintaining quality assurance information, as well as to streamline clerical duties in the medical staff office, El Camino Hospital (a 460-bed acute care facility in Mountain View, California) developed a comprehensive, computerized medical staff quality assurance database (MESQUAD). This article describes MESQUAD as a program developed by one hospital to meet its unique needs. PMID- 3095763 TI - An office of medical practice evaluation: what is it and why have one? PMID- 3095764 TI - Monitoring and evaluation of the quality and appropriateness of care: a hospital example. Joint Commission on Accreditation of Hospitals. PMID- 3095765 TI - [Experience with early postoperative feeding through a needle-catheter jejunostomy]. PMID- 3095767 TI - Are DRGs cost containment vehicles? PMID- 3095766 TI - [Prenatal diagnosis of Sanfilippo A disease (mucopolysaccharidosis IIIA)]. PMID- 3095768 TI - Physicochemical hair conformation of patients with Sanfilippo disease type IIIA. AB - Sanfilippo disease type IIIA is an inborn error of metabolism with a deficiency in the heparan sulfamidase. Besides severe psychomotor retardation hair changes are obligatory. Hair is found to be coarse like a brush. We applied X-ray diffraction and infrared spectroscopy to characterize the conformation of hair samples of Sanfilippo patients. In healthy subjects as well as in the affected hair samples we found the wave numbers of structural relevance 1450, 1500, 1630, 1730, the pair 2337 and 2362, the quadruplet 2850, 2870, 2917, 2930 and 3080 cm 1. Also on X-ray diffraction analysis no differences could be detected. Though morphological-macroscopically and microscopically-changes were described for Sanfilippo hair samples, we could not find any change in supramolecular structure. The physical properties of coarseness of those hair specimen seems to be due to differences in the structural assembly of hair fibres and storage of heparan sulfate. PMID- 3095769 TI - [Dwarfism in the Alagille syndrome caused by somatomedin C deficiency?]. AB - Alagille syndrome (= arterio-hepatic dysplasia) is a rare congenital syndrome consisting of cholestasis with paucity of intrahepatic bile ducts, pulmonary artery stenosis, skeletal anomalies and typical facies. Growth retardation, which is not correlated with vertebral anomalies or the degree of cholestasis, occurs in about two thirds of patients. We report on hormonal aspects of growth retardation in an 8 year old Austrian boy with the typical features of arteriohepatic dysplasia. Thyroid function and a cortisol profile were normal and we found normal HGH response to insulin stimulation. The Somatomedin C-activity was well below the age-adjusted normal range. Even after test-induced HGH peaks no increase in Somatomedin C-activity could be observed. A six month course of phenobarbital-, cholestyramine- and D-penicillamine-therapy led to significant improvement of cholestasis, however Somatomedin C values and growth velocity remained unchanged. Results in our patients show that Somatomedin C-deficiency might be an important cause of growth retardation in children with chronic liver disease, at least in arteriohepatic dysplasia. PMID- 3095770 TI - [Carbamazepine (Tegretol) monotherapy in epilepsies with partial and/or secondary generalized seizures in childhood and adolescence]. AB - The effectiveness and side effects of a carbamazepine monotherapy were evaluated in 40 children and adolescents (22 boys and 18 girls with an age distribution between 1 and 16 years) over a period of 6 years. In addition the attempt has been made, to find correlations between sex, age of seizure onset, aetiology of the disease, types of seizures, and EEG-abnormalities on the one hand, and the clinical response to the drug on the other. Selection criteria were, that the patients were under continuous follow-up, that they suffered from partial or/and secondarily generalized seizures and that Tegretol was the first and only drug at the beginning of the examination. The treatment with the Carbamazepine monotherapy was successful in 63% of the patients, 37% remained resistant to the treatment. Carbamazepine proved to be effective against partial seizures as well as secondarily generalized grand-mal-seizures. The therapeutic range of the serum carbamazepine levels during monotherapy varied between 15-35 mu Mol/l. 40 patients entered, 38 completed the study. In two cases the drug had to be stopped owing to allergic skin rash due to the drug. No other serious side effects were observed in any of the remaining 38 patients. The most frequent laboratory changes were an increase of Gamma-GT and leucopenia. All the cases who became seizure-free (Responder) were compared with the remaining cases with unfavourable treatment results (Nonresponder) in order to find out whether there are significant differences between the two groups, as far as sex, age ... etc. (see above) are concerned.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095771 TI - [Epileptic seizures in childhood: classification, diagnosis, therapy]. AB - This is a review about epilepsies of childhood dealing with the elementary principles in classification, diagnosis and treatment. In each case of a patient suffering with epilepsy 3 diagnoses have to be made: the diagnosis of the seizure type, the diagnosis of the epilepsy-type, the diagnosis of the etiology. The seizure-type has to be diagnosed as generalized (e.g. grand mal, absence seizure) or partial (simple or complex) which can be obtained from the clinical picture and EEG. The classification of seizures is different from the classification of epilepsies: recurrent seizures, only a single type or more types in the same patient, make the diagnosis of the epilepsy-type. The etiologic diagnosis is often not possible to make and requires careful judgment in the use of special procedures; however, the diagnosis of the seizure-type includes their etiology in as much as, for example, awake-grand mal and absence seizures can be classified as idiopathic resp. sleep-grand mal and partial seizures as symptomatic. The most essential principle for the treatment of epilepsies is: the seizures diagnosis determines the appropriate therapy. The drugs of choice for partial seizures and most cases with grand mal are phenytoin and/or carbamazepine; absence seizures and benign myoclonic seizures highly respond to valproate; atonic seizures are most resistant to therapy. To make an effective treatment you have to know the dose, the therapeutic plasma drug level, the drug's half life and the side effects. The aim of epilepsy-treatment has to be: avoidance of seizures without side-effects. PMID- 3095772 TI - [In-vivo bacteriostatic and bactericidal activity of pefloxacine]. AB - After oral ingestion of pefloxacin (400 mg every 12 hours for four days), the following characteristics were studied: bacteriostatic and bactericidal activity of urine for controls free of urinary tract infection on 6 "test" strains; kinetics of bacteriostatic and bactericidal activity of urine as compared to serum in patients with urinary tract infection. The urinary bacteriostatic level approximates bactericidal levels in healthy individuals. This level, that varies across bacterial species, remains steady between the third hour and the twenty fourth hour following initiation of treatment: values found were 1/16 to 1/8192 for enterobacteria, 1/64 to 1/256 for Pseudomonas aeruginosa and 1/256 to 1/512 for Staphylococcus aureus. In patients, urinary killing curves show that bacteriuria decreases by 5 Log10 approximately, starting at the third hour. Urine was sterile by the sixth hour. In most cases, serum bacteriostatic activity was above 1/32 throughout treatment, with maximum levels being recorded on the fourth day (above 1/64). Bactericidal activity is similar to bacteriostatic activity. PMID- 3095773 TI - [In-vitro activity of cefonicid on hospital bacteria. Regression line and proposal for critical values]. AB - Antimicrobial activity of cefonicid, a new second generation cephalosporin, against 315 hospital isolates (4th trimester 1984) was investigated. E. coli and Proteus mirabilis were the most susceptible species. All E. coli strains except one were inhibited at 8 mg/l (modal MIC: 0.5); MICs of all indole + Proteus were 8 mg/l (modal MIC: 0.06). Another group was moderately susceptible: MICs of Klebsiella and Citrobacter ranged from 0.12 to 128 mg/l, but MICs of 50% of these strains were less than or equal to 4 mg/l; MIC was less than or equal to 8 mg/l for 75% of indole + Proteus and Providencia strains; tested Proteus vulgaris were especially resistant (MICs greater than 128 mg/l). Most Enterobacter and Serratia strains showed little susceptibility (modal MIC for both species greater than or equal to 128 mg/l). MICs of all tested Pseudomonas aeruginosa strains were greater than 128 mg/l. 20 of the 24 tested Acinetobacter strains had a MIC of greater than or equal to 128 mg/l. For Staphylococcus aureus, 88% of methicillin sensitive strains were inhibited by concentrations of 2 to 4 mg/l whereas methicillin-resistant strains were resistant to cefonicid (75%: MIC greater than 64 mg/l). Enterococci were resistant to cefonicid. A correlation curve was established (Enterobacteria and Staphylococci). On the basis of cefonicid's pharmacokinetic characteristics, critical concentrations are proposed. PMID- 3095774 TI - [Bacteriostatic activity of azlocillin, gentamycin, amikacin singly or in combination on 200 strains of Pseudomonas aeruginosa]. AB - In vitro activity of azlocillin, gentamicin, and amikacin, alone or in combination was evaluated against 200 clinical isolates of Pseudomonas aeruginosa. The minimum inhibitory concentrations (MICs) were determined by a standard technique. For the evaluation of synergistic activities, one antibiotic was added in a concentration equivalent to one-fourth its MIC to increasing concentrations of the other antibiotic. The MIC for 50% of the strains was 3.25 micrograms/ml for gentamicin, 3 micrograms/ml for amikacin and 7 micrograms/ml for azlocillin. No significant difference could be seen between the two combinations, the percentage of synergy was 37% for azlocillin-gentamicin and 36% for azlocillin-amikacin. No antagonism was observed. PMID- 3095775 TI - [Beta-lactamase induction in Pseudomonas aeruginosa by cefpiramide and 3 other antipyocyanic cephalosporins]. AB - Cefpiramide (SR 95445) (CPM) is a new cephalosporin with activity against Pseudomonas and a good bioavailability following parenteral administration. This drug is a first rather than second choice treatment in Pseudomonas infections. For this reason, investigation into cefpiramide's capacity to induce beta lactamase production is especially interesting. A heavy inoculum of P. aeruginosa NCTC 8203, a strain that produces and inducible cephalosporinase (pI = 8.7) was incubated for 4 hours with CPM, cefsulodin (CFS), cefoperazone (CPZ) and ceftazidime (CTZ) in various concentrations. After collection and sonic treatment of the bacteria, the beta-lactamase activity was assayed using an acidimetric method and expressed as units of enzyme activity per mg proteins in the cell-free extract. The smallest increase in beta-lactamase production was recorded with CPM. The strongest inductor was CTZ. CFS and CPZ had an intermediate effect. PMID- 3095776 TI - [Bactericidal activity of cefpiramide on P. aeruginosa using an in vitro pharmacokinetic simulation model]. AB - Cefpiramide (CPM) is a new cephalosporin with good activity against Pseudomonas. Sustained high serum concentrations are observed. We studied CPM killing kinetics using an in vitro model that simulates the pharmacokinetic profile observed in humans following a single intramuscular injection. The strain tested was Pseudomonas aeruginosa NCTC 8203. CPM was compared to cefoperazone (CPZ), cefsulodin (CFS) and ceftazidime (CTZ). These drugs differed only for the time interval to bacterial regrowth that was in the following ascending order: CFS, CPZ, CTZ and CPM. This finding corroborates the fact that cefpiramide's pharmacokinetic properties allow wider space intervals between doses than for other drugs. PMID- 3095777 TI - [Acute reversible agranulocytosis during ceftriaxone treatment]. AB - A 75-year-old man developed acute transient agranulocytosis. Hematologic data and course were suggestive of a toxic etiology. The patient had been admitted for pneumococcal septicemia and a polymicrobial abscess of the soft tissues of the left leg. At the time of diagnosis of the agranulocytosis, he had received 36 g ceftriaxone. The agranulocytosis resolved following discontinuation of ceftriaxone. This drug was, in all likeliness, responsible for the hematologic disorder. Renal failure occurred concomitantly with the agranulocytosis. Other similar cases have been reported. In view of these data, blood counts should be monitored in patients receiving prolonged courses of ceftriaxone. PMID- 3095778 TI - [Contribution of potentiometry in the presence of lipoic acid to the study and evaluation of the in vitro antibacterial effects of betalactams]. AB - We used potentiometry to assess the reduction of lipoic acid by a culture of Escherichia coli incubated with a beta-lactam. Two significant chronometric parameters were determined: one evaluates the antibiotic's killing effect, while the other reflects the stimulative effect exerted by the drug on cell reductive activity. For different beta-lactams, we did a quantitative study of the relationship between the concentrations of the antibiotic and each of the two potentiometric parameters. On the basis of our results we classified the different beta-lactams according to the degree of their killing and stimulative effects. Our study shows that potentiometry can provide original quantitative information on the in vitro antibacterial effect of beta-lactams. PMID- 3095779 TI - [Present status of the sensitivity of Pseudomonas aeruginosa to aminoglycosides in France]. AB - 9,119 strains of P. aeruginosa were collected from 10 French hospitals from 1981 to 1984. The MIC of gentamicin (GM), sisomicin (SIS), tobramycin (TOB), dibekacin (DBK), netilmicin (NET), amikacin (AMK), and habekacin (HBK) was determined by the two fold microdilution method. 81% of the strains were susceptible to the 4 aminoglycosides. The MICs (geometric mean, mg/l) for these susceptible strains were: GM: 1.69, SIS: 1.58, TOB: 1.06, DBK: 1.12, NET: 2.73, AMK: 4.16, HBK: 2.70. 19% of the 9 119 strains were resistant to SIS, 18% to GM, 16% to TOB and DBK, 11% to NET, 3% to AMK and HBK. Among the 1 758 strains resistant to one or several aminoglycosides, the frequency of the resistance phenotypes was GM-SIS: 11%, GM-SIS-NET: 4.95%, GM-SIS-TOB-DBK: 32.7%, GM-SIS-TOB-DBK-NET: 34.45%, SIS TOB-DBK-NET: 2.5%, SIS-TOB-DBK-NET-AMK-HBK: 2.39%, GM-SIS-TOB-DBK-NET-AMK-HBK: 11.61%. The mechanism of resistance of the phenotypes 1 to 6 is enzymatic. The mechanism of resistance of the phenotype 7 (resistance to the six aminoglycosides) is either enzymatic or due to decreased uptake or penetration of antibiotic. HBK and AMK are the aminoglycosides most frequently active against P. aeruginosa. The patterns of resistance to both antibiotics are the same. On a weight-for-weight basis, HBK is more active than AMK. PMID- 3095780 TI - [Intestinal decontamination in the neutropenic patient. Apropos of a prospective randomized study]. AB - Sixty-five patients undergoing remission-induction chemotherapy for acute leukemia in a protected environment unit were randomly assigned to selective antimicrobial modulation of the intestinal flora (SAM) with trimethoprim sulfamethoxazole, or total antibiotic decontamination (TAD) with gentamicin, vancomycin and colimycin. Digestive tract colonization with Streptococcus D was more prevalent in the SAM group (p less than 0.01); colonization with yeasts was more prevalent in the TAD group (p less than 0.001). However, there was no difference between the two groups as regards to clinically and microbiologically documented infections, septicemias and survival. Selective antimicrobial modulation with trimethoprim-sulfamethoxazole is as effective and cheaper than total antibiotic decontamination with gentamicin, vancomycin and colimycin. PMID- 3095781 TI - Indium 111 white blood cell scanning in the pediatric population. AB - Indium-111 leukocyte scanning is a reliable means of locating acute infection in adults, but its use in the pediatric population has not been extensively documented. The results of scans on 30 children retrospectively reviewed are presented. Acute infections were detected in 15 of 16 patients (94% sensitivity) with one false negative scan. There were 8 truly negative and 6 falsely positive studies (57% specificity). PMID- 3095782 TI - 19S IgM rheumatoid factor-7S IgG rheumatoid factor immune complexes isolated in sera of patients with juvenile rheumatoid arthritis. AB - 19S IgM rheumatoid factors (RF) and hidden 19S IgM RF have been associated with increased disease activity in juvenile rheumatoid arthritis (JRA). Recently, immune complexes (IC) were isolated from JRA sera by several methods which demonstrated the presence of 19S IgM RF. The present study evaluates 25 JRA patients' sera by separation on a Sepharose 4B column to which were bound F(ab')2 fragments of goat IgG antihuman IgM antibody to separate IgM-containing IC. The columns were sequentially eluted with 1 M ammonia and 0.1 M glycine-HCl buffer, pH 3.0. The isolated fractions were assayed for 19S IgM RF and 7S IgM RF by ELISA, IgG levels by immunodiffusion, and by preparative isoelectric focusing. The ammonia eluate from the alpha HIgM column revealed IgG, 19S IgM RF in six patients, and IgM RF in four patients. All were polyarticular-onset JRA patients. In the glycine-HCl eluate of sera, 19S IgM RF and IgG were also detected in 15 patients, all six seropositive, polyarticular-onset, six seronegative, polyarticular-onset, and three pauciarticular-onset patients. Significant 7S IgG RF titers were demonstrated in the glycine-HCl eluates of six patients, five seropositive, polyarticular-onset patients, and one seronegative, polyarticular onset patient. Analysis by preparative isoelectric focusing of the IgM RF and IgG RF positive ammonia and glycine-HCl eluates showed IgM RF throughout the pH range (4-10), but the highest amount of IgM RF was in the pH range 4.0-5.5. Significant IgG RF titers were detected only in this restricted spectrotypic area of pH 4.0 5.5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095783 TI - Response of the maternal, fetal, and neonatal pituitary-thyroid axis to thyrotropin-releasing hormone. AB - Thyrotropin releasing hormone (TRH) readily crosses the placenta and stimulates the fetal pituitary. We studied the response of the maternal and fetal pituitary thyroid axes to TRH and the influence of prenatal exposure to TRH on the physiological postnatal increase in thyrotropin (TSH) and triiodothyronine (T3) in the neonate. Twenty-six pregnant women received TRH (400 or 600 micrograms) intravenous or saline (controls) either 2 or 12 h before elective cesarean section at term. Administration of 400 micrograms of TRH resulted in significant elevations of maternal TSH (15.7 +/- 2.9 versus 3.2 +/- 0.4 microU/ml, p less than 0.01) and prolactin (416 +/- 94 versus 223 +/- 41 ng/ml, p less than 0.05) 2 h later. Maternal T3 remained unchanged. A higher dose of TRH (600 micrograms) produced comparable results. Maternal administration of TRH (400 micrograms) 2 h before delivery resulted in significant increases in fetal TSH and T3 over controls (21.1 +/- 3.7 versus 4.8 +/- 1.0 microU/ml, and 132 +/- 12 versus 64 +/- 9 ng/dl, p less than 0.01, respectively). Cord blood hormone levels 12 hours after TRH administration were similar to controls. Higher doses of TRH did not produce further increases in fetal TSH or T3. Control and treated neonates demonstrated similar physiological postnatal increases in TSH and T3, suggesting that prior exposure to TRH did not blunt this response. These data suggest that maternal administration of TRH is an effective way of increasing fetal T3 levels, and that this treatment does not inhibit the postnatal surge in TSH and T3. PMID- 3095784 TI - [Continuous nocturnal intragastric feeding in glycogenosis type I and III]. AB - Three patients with type I glycogen storage disease (GT I) and four patients with type III glycogen storage disease (GT III) have been treated with nocturnal intragastric feeding and frequent daytime meals for 2 to 8.5 years. In all of them, hypoglycemia was well controlled. Patients with GT. I showed a normal growth rate and an improvement of serum lactate, triglycerides, cholesterol and urate. Patients with GT. III showed no consistent changes in serum triglycerides cholesterol and transaminases and no improvement of myocardiopathy. PMID- 3095785 TI - [Intolerance to the proteins of cow's milk. II. Diagnosis, etiopathogenesis, treatment]. PMID- 3095786 TI - Transmural gradient of tissue gas tensions in the canine left ventricular myocardium during coronary clamping and reactive hyperemia. AB - Mass spectrometry was used for the continuous, simultaneous and quantitative measurement of oxygen (PO2) and carbon dioxide (PCO2) partial pressures in the subendocardial and subepicardial layers of the left ventricle in 11 anaesthetized ventilated dogs. Under control conditions, PO2 was significantly lower in the subendocardium (13.5 +/- 4.5 mm Hg) than in the subepicardium (20.7 +/- 2.3 mm Hg), whereas PCO2 did not differ significantly (43 +/- 8.8 and 51 +/- 9.2 mm Hg respectively). These variables were not correlated with blood pressure or coronary blood flow. Subendocardial and subepicardial PO2 decreased less than 5 s after coronary occlusion. These changes were more rapid and severe in the subendocardium. After occlusion for 90 s: subendocardial PO2 was 4.1 +/- 6.3 mm Hg while subepicardial PO2 was 6.7 +/- 15.0 mm Hg (P less than 0.05). PCO2 reached peak values of 56 +/- 25 mm Hg subendocardial and 82 +/- 22 mm Hg subepicardial at 2.67 +/- 0.71 min and 3.43 +/- 0.93 min after coronary clamping. A reactive hyperemia occurred after coronary unclamping with different time courses and amplitudes for systolic and diastolic stroke flows while PO2 recovered with different kinetics. Subendocardial PO2 increased with a lower initial slope, probably in relation with the delay in the diastolic hyperemia. The observed delayed subendocardial hyperoxia, unrelated to the hyperemia, may indicate a delay in the recovery of normal work and metabolism in the inner layers of the myocardium. PMID- 3095787 TI - Coupling of metabolic CO2 production to ion transport in isolated rat thick ascending limbs and collecting tubules. AB - Metabolic CO2 production from appropriate [U-14C]-labelled substrates (either L lactate or D-glucose) was measured in single pieces of tubule as previously described (Le Bouffant et al. 1984). Changing the incubate osmotic pressure by mannitol addition resulted in an increase in oxidative metabolism which was more marked in outer-medullary segment MAL and MCT) than in cortical segments (CAL and CCT). Availability of metabolic substrate was not rate limiting under these conditions because FCCP addition (1 mumol X l-1) produced a marked rise in CO2 production in these structures. Ouabain (1 mmol X l-1) decreased by more than 50% the CO2 production by CAL, MAL, CCT and MCT samples, indicating that the larger part of oxidative metabolism was coupled to active Na transport. Furosemide addition (10(-5) mol X l-1) to CAL and MAL samples, or amiloride addition (10(-4) mol X l-1) to CCT and MCT samples reduced the rate of CO2 production to an extent almost similar to that obtained with ouabain, an observation suggesting that apical entry of Na+ was present in these non-perfused tubules. Finally, the effects of changing the concentration of either K+ or Cl- was tested in CAL samples. K+ suppression greatly depressed the rate of CO2 production. Replacement of chloride with sulfate also decreased this rate to an extent similar to that observed with furosemide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095788 TI - Isolation of Bacillus subtilis in connection with bovine mastitis. AB - Bacillus subtilis has only seldom been associated with pathological conditions in mammals. As the organism is considered to be ubiquitous in the environment, care has to be taken not to put too much emphasis on the pathogenicity of the organism, even in cases where it is isolated in pure culture. Bacillus subtilis was isolated from 17 cases of bovine mastitis in which it was considered to be the etiological factor. PMID- 3095789 TI - In situ dot blots: quantitation of mRNA in intact cells. AB - A rapid, simple and reproducible dot blot method is described for quantitating the amounts of specific messages in small numbers of intact cells. The method has been used to accurately determine the number of histone H4 mRNA molecules in growing (approximately 40,000) and in starved (approximately 1600) Tetrahymena thermophila, and to measure the amount of message contributed by an E. coli plasmid containing part of the S10 ribosomal operon. Use of the method is illustrated to optimize in situ hybridization protocols and to measure mRNA amounts in cell lysates. Preliminary studies also indicate that the method can be used to detect mRNA in intact yeast cells. PMID- 3095790 TI - Coding sequence of a ferredoxin gene from Anabaena variabilis ATCC 29413. PMID- 3095791 TI - Coding sequence of a ferredoxin gene from Anacystis nidulans R2 (Synechococcus PCC7942). PMID- 3095792 TI - One aspartic acid transfer RNA gene is present upstream of the U6 snRNA gene cluster in Drosophila melanogaster. PMID- 3095794 TI - Two or more copies of Drosophila heat shock consensus sequence serve to activate transcription in yeast. AB - A synthetic oligonucleotide bearing the Drosophila heat shock consensus sequence confers heat inducibility on a CYC1-lacZ gene in Saccharomyces cerevisiae. This sequence CTGGAATTTTCTAGA was inserted in place of the upstream activation sites of the CYC1 promoter adjacent to CYC1 TATA boxes. These constructs were transformed into yeast and found to be heat-inducible when two or more inserts were present. The level of inducibility seemed to increase with the number of inserted sequences: however, the orientations of these sequences relative to each other did not have much effect. PMID- 3095793 TI - Synthesis and properties of oligonucleotides containing 2'-deoxynebularine and 2' deoxyxanthosine. AB - The preparation of synthetic oligonucleotides containing 2'-deoxynebularine (dN) and 2'-deoxyxanthosine (dX) is described. The thermal stabilities of duplexes containing dX, dN, and 2'-deoxyinosine (dI) base-paired with the four natural bases have been measured. Xanthine base pairs have stabilities at pH 5.5 that are similar to those of dI-containing duplexes at neutral pH. When xanthine is paired with adenine or cytosine an unusual stabilization of the duplex structure is observed at acid pH. Incorporation of base mispairs opposite template xanthine sites were measured using Drosophila DNA polymerase alpha. The relative nucleoside incorporation rates are in the order: T greater than C much greater than A approximately equal to G. These rates do not correlate with relative thermodynamic stabilities of base mispairs with xanthine obtained from Tm measurements: T greater than G greater than A approximately equal to C. We suggest that DNA polymerase misinsertion rates are greatest when the base mispair can be formed in accordance with Watson-Crick as opposed to other base pairing geometries even though other geometries, e.g. wobble, may result in a more stable final DNA product. PMID- 3095796 TI - New for old. PMID- 3095797 TI - Effect of antioxidants on mutagenesis induced by DMBA in human cells. AB - The effect of vitamin A palmitate (VAP), vitamin A acetate (VAA), 2,3-tert-butyl 4-hydroxyanisole, and 2,6-di-tert-butyl-p-cresol (BHT) on mutagenesis induced by 7,12-dime-thylbenz[a]anthracene (DMBA) was examined in a human epithelial-like cell line. Cultures were exposed to DMBA with or without the antioxidant compound, and mutation frequencies were determined by selection against diphtheria toxin. A clear inhibition of mutagenesis was observed particularly with VAA and BHT. PMID- 3095795 TI - Functional analysis of the murine IgH enhancer: evidence for negative control of cell-type specificity. AB - We have carried out a mutational analysis of the mouse IgH enhancer. Consistent with previous reports, deletions extending from either the 5' side or the 3' side of the enhancer fail to reveal distinct boundaries which define enhancer function in lymphoid cells. Interestingly, internal point mutations and deletions within the "enhancer core" regions fail to identify any necessary functional role for these conserved elements. When tested in CV1 cells, which do not normally respond to the IgH enhancer, certain deletions exhibit significant enhancer activity. We take these findings to indicate that the functional domains of the IgH enhancer are complex and that cell type specificity is defined in part by negative factors present in non-lymphoid cells. PMID- 3095798 TI - Impact of prophylactic therapy for postoperative thromboembolism on prospective payment. AB - Widescale implementation of prospective payment systems as a means of reimbursing hospitals on the basis of diagnosis-related group designation has important implications with respect to the selection of drug therapy. Instead of analyzing costs on a departmental basis, pharmacists need to identify the impact of optimal drug therapy on overall profitability. Clinically evident deep venous thrombosis and pulmonary embolism occur in approximately 3.5% and 1.8% of patients undergoing general surgery. Treatment of these complications consumes hospital resources, but the hospital absorbs the cost of treatment under the prospective payment system. Effective prophylactic measures increase profitability by preventing complications and minimizing the proportion of outliers due to increased length of stay. In selecting prophylactic measures, this impact on overall profitability is as important as acquisition cost. For example, in comparison with no prophylaxis, dihydroergotamine-heparin reduces the frequency of deep venous thrombosis in patients undergoing general surgery by 61.5% and heparin alone reduces it by 31.2%. The relative effect of this combination on postoperative complications and resultant savings in terms of treating them compensates for differences in acquisition costs between these measures. PMID- 3095799 TI - Influence of endogenous growth hormone-releasing factor (GRF) on the secretion of GH during the perinatal period in the rat. AB - Passive immunization of pregnant rats with a specific antiserum to rat GRF (GRF AS) is followed by a decrease in fetal serum GH on the 19th day of gestation. A significant reduction in serum GH is still observed in older fetuses and newborn rats. Pituitary GH content increases in 19- and 20-day-old fetuses after GRF-AS administration to their mothers. These results suggest that endogenous fetal hypothalamic GRF (or placenta GRF) play a physiological role in the secretion of pituitary GH as early as the 19th day of fetal life and may be responsible for the peak of GH release that occurs in fetuses at the end of gestation. PMID- 3095800 TI - [Use of nitroglycerin in patients after surgical treatment of coronary disease]. PMID- 3095801 TI - Effect of disulfiram on function of the liver of rats with galactosamine-induced hepatitis. AB - This study was aimed to examine whether disulfiram (DS) may exacerbate the pre existing liver damage induced by D-galactosamine (GalN) in rats. DS, 600 mg/kg, administered by gavage for 3 days caused an increase in asparagine aminotransferase (AspAT) and alkaline phosphatase (AP) and a decrease in cholinesterase (ChE) activity in the serum and decrease in AspAT and ChE activity in the liver. DS given to rats with GAlN-induced liver injury caused significant increase in alanine aminotransferase (A1AT) and bilirubin level in serum in comparison with rats with GalN-damaged liver but without DS treatment. In summary, DS exacerbates a damage of the liver of rats. This study supported the clinical observations showing enhanced liver damage in alcoholics treated with DS. PMID- 3095802 TI - The ejaculatory behavior of sexually sluggish male rats treated with (-)deprenyl, apomorphine, bromocriptine and amphetamine. AB - Bromocriptine (0.5 mg/kg) and apomorphine (0.03 mg/kg) exert moderate aphrodisiac effect in sexually sluggish rats. This effect appears rapidly and reaches its peak within 24 h. Amphetamine (2 mg/kg) acts similarly but with a more rapid onset and offset of the effect. A single dose of (-)deprenyl, a selective inhibitor of MAO-B, exerts a much more potent effect in this test. PMID- 3095803 TI - Biological implications of androgen dependent changes in proton-NMR relaxation times in rat ventral prostate. AB - The present studies were conducted in rat ventral prostate to determine if proton nuclear magnetic resonance (1H-NMR) might be a useful tool to monitor physiologic changes in an androgen-dependent target tissue after ablation and reconstitution. Ventral prostate mass and blood flow (86RbCl distribution) decreased markedly after castration. Although prostate water content was not affected by androgen ablation, 1H-NMR spin-lattice (T1) and spin-spin (T2) relaxation times determined on excised prostate tissue were reduced by 10% and 50%, respectively. Testosterone propionate (Tp) reconstitution resulted in a prompt but transient increase in total water content, marked increases in prostate blood flow, and regrowth of the gland. 1H-NMR studies indicated that although T1 lengthening after Tp was temporally related to changes in prostate water content, T1's remained prolonged after total prostate water content returned to control levels. Increased Gd-DTPA-dimeg modification of prostate T1 by Gadolinium-DTPA-dimethyl glucamine in androgen reconstituted rats implied that prostate extracellular water volumes were markedly increased during intervals of increased T1. Recovery of prostate T2 relaxation times after Tp was delayed with respect to changes in T1, water content, and prostate blood flow, but was temporally correlated with increase in prostate dry mass. Studies to assess Gd-DTPA-dimeg T2 modification showed that prostate T2 changes after androgen depletion and replacement reflected spin-spin relaxation of water protons outside the in vivo Gd-DTPA-dimeg distribution volume. The results from these studies indicate that 1H-NMR and paramagnetic probes may be useful to noninvasively monitor biologically relevant changes in cellular and extracellular water in androgen-dependent target tissues during hormonal manipulations. PMID- 3095804 TI - Idiopathic chondrolysis of the hip: an ultrastructural study of the articular cartilage of the femoral head. AB - Core biopsies obtained from the articular cartilage of the femoral head of a 16 year-old girl with idiopathic chondrolysis of the hip were subjected to an ultrastructural study. Zone I was missing and zone II was the most superficial layer present in the articular cartilage of our patient. Collagen fibrils were thinner than normal and more uniform in diameter, and proteoglycans were normally distributed among them. Degenerating chondrocytes were found, as well as debris of dead cells, but many chondrocytes were still vital and engaged in active synthesis. Most of the chronic degenerative changes observed in ultrastructural studies on osteoarthritis were not observed in this case of idiopathic chondrolysis which seems to be, on the basis of our findings, a pathological process which develops and runs its course very quickly. PMID- 3095806 TI - [The dental assistant in the application of sealants]. PMID- 3095807 TI - [Dental knowledge in a group of assistants]. PMID- 3095805 TI - Traumatic transformation of unicameral bone cyst into aneurysmal bone cyst. PMID- 3095808 TI - [Behavior suggestions]. PMID- 3095809 TI - [Control of plaque in interdental spaces]. PMID- 3095810 TI - [The dam: a technic to isolate the surgical field]. PMID- 3095811 TI - [Administration and secretarial delegation]. PMID- 3095812 TI - [Chemico-physical aspects of sealants]. PMID- 3095813 TI - [Health education for prevention. I]. PMID- 3095814 TI - [Prevention in a Lazio school]. PMID- 3095815 TI - [The toothbrush: standards and technics of use]. PMID- 3095816 TI - [Operational procedures: meaning and method]. PMID- 3095817 TI - [Problems of hygiene and prevention in dental offices]. PMID- 3095818 TI - [Oral hygiene and dental pathology due to hydantoin]. PMID- 3095821 TI - Short P-R intervals and tachyarrhythmias in Fabry's disease. PMID- 3095820 TI - Impaired thyrotrophin secretion following the administration of thyrotrophin releasing hormone in type II diabetes mellitus. AB - Serum thyrotrophin has been measured before and after the intravenous administration of 200 micrograms of thyrotrophin-releasing hormone in 91 white subjects (33 stable diabetic patients and 58 healthy controls), none of whom had any clinical evidence of thyroid or pituitary dysfunction. Seven of the diabetic subjects failed to achieve a rise of serum thyrotrophin of greater than 2 mU/l above basal concentrations, as compared with only one of the control subjects (P = 0.006). The difference in response between diabetics and controls was confined to patients with Type II (non-insulin-dependent) diabetes: thus 5 of 13 Type II patients and 2 of 20 Type I (insulin-dependent) patients failed to show a normal response to thyrotrophin releasing hormone injection. No significant effect of glycaemic control on thyrotrophin responses was noted. These results suggest that Type II diabetes mellitus may be a cause of impaired thyrotrophin secretion in patients with no clinical evidence of pituitary disease. The mechanism for this impaired pituitary hormone release remains to be clarified. PMID- 3095822 TI - Improvement of body weight and nitrogen balance of chicks fed histidine-free or lysine-free diets with supplementation of graded levels of sulfur-containing amino acids. AB - To demonstrate the nutritional specificity of essential amino acids, body weight change and nitrogen balance were compared in chicks equalized-fed a histidine free or lysine-free diet with 0, 20, 40, 60, 80, or 100% requirement of sulfur containing amino acids (SAA). With an increase of SAA level up to 40% of its requirement, body weight and nitrogen balance increased irrespective of complete deficiency of histidine or lysine. Above 40% of the SAA requirement, these parameters reached plateaus. The intersection points of the two regression lines at which the responses of body weight change and nitrogen balance altered were 49.8 and 52.1% in the chicks fed the histidine-free diet and 44.7 and 32.6% in the chicks fed the lysine-free diet, respectively. These values are quite agreeable with the estimate of the nutritional score of the amino acid mixtures in an earlier report (Kino and Okumura, 1986). It was demonstrated that the effect of essential amino acid deficiency does not always directly associate with the percentage deficit relative to its requirement, and there exists nutritional specificity of essential amino acids. PMID- 3095823 TI - [Roentgen findings in patients with long-term artificial respiration]. PMID- 3095819 TI - Review of general surgery 1985. PMID- 3095824 TI - [Clinico-anatomical and microbiological research on the residual changes following spontaneously cured tuberculosis]. PMID- 3095825 TI - [Growth of Mycobacterium tuberculosis L forms on semipermeable cellophane membranes]. PMID- 3095826 TI - [A case of juvenile xanthogranuloma of the lung]. PMID- 3095828 TI - Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. AB - DNA coding for bacteriophage T7 RNA polymerase was ligated to a vaccinia virus transcriptional promoter and integrated within the vaccinia virus genome. The recombinant vaccinia virus retained infectivity and stably expressed T7 RNA polymerase in mammalian cells. Target genes were constructed by inserting DNA segments that code for beta-galactosidase or chloramphenicol acetyltransferase into a plasmid with bacteriophage T7 promoter and terminator regions. When cells were infected with the recombinant vaccinia virus and transfected with plasmids containing the target genes, the latter were expressed at high levels. Chloramphenicol acetyltransferase activity was 400-600 times greater than that observed with conventional mammalian transient-expression systems regulated either by the enhancer and promoter regions of the Rous sarcoma virus long terminal repeat or by the simian virus 40 early region. The vaccinia/T7 hybrid virus forms the basis of a simple, rapid, widely applicable, and efficient mammalian expression system. PMID- 3095827 TI - Role of epididymal inflammation in the induction of dominant lethal mutations in Fischer 344 rat sperm by methyl chloride. AB - This study assessed the possible relationship between methyl chloride (MeCl) induced epididymal inflammation and the formation of dominant lethal mutations in sperm of Fischer 344 rats. Groups of 40 males were exposed to MeCl (3000 ppm 6 hr/day for 5 days), with or without concurrent treatment with the anti inflammatory agent 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW 755C; 10 mg/kg, i.p. 1 hr pre- and postexposure); BW 755C was shown previously to inhibit MeCl-induced epididymal inflammation. Control groups (n = 20) were either untreated, injected as described above with BW 755C, or injected on the afternoon of day 5 with triethylenemelamine (0.2 mg/kg), a known dominant lethal mutagen. Each male was caged with one female weekly for 3 weeks; 12-18 days after mating, females were killed to assess dominant lethal parameters. In females bred to MeCl exposed males, significant increases were observed in postimplantation loss at postexposure week 1 (0.84 dead implants per female vs. 0.29 in untreated controls) and in dead implants/total implants at both week 1 (0.10 vs. 0.04 control) and week 2 (0.24 vs. 0.06 control). These increases were not observed in females bred to males treated with BW 755C during MeCl exposure. Coadministration of BW 755C to males along with MeCl also reduced the percentage of mated females with two or more postimplantation losses from 31% to 8% (week 1) and 30% to 12% (week 2). Therefore, the dominant lethal mutations induced by MeCl appear to be a consequence of its induction of inflammation in the epididymis. These data demonstrate the potential genotoxicity of inflammatory processes in vivo. PMID- 3095829 TI - Response of two pea hybrids to CO2 enrichment: a test of the energy overflow hypothesis for alternative respiration. AB - Two pea (Pisum sativum L.) hybrids differing in the presence or absence of the cyanide-resistant (alternative) pathway of respiration were constructed by reciprocally crossing cv. Alaska and cv. Progress No. 9. The F1 hybrids were grown in greenhouses maintained at either 350 or 650 ppm CO2, and the growth, flowering, and dry matter accumulation were compared. The objective was to assess the significance of the alternative respiratory pathway to whole-plant carbon budgets and further to test the hypothesis that the alternative pathway is important in oxidizing excess carbohydrates such as might accumulate under conditions of CO2 enrichment. More carbohydrates were available in the F1 hybrid lacking the pathway, as evidenced by greater plant height, leaf area, specific leaf weight, and total dry matter compared with the reciprocal hybrid, especially at 650 ppm CO2. Specific leaf weight increased markedly under CO2 enrichment in the hybrid lacking the pathway, while it was the same at 350 and 650 ppm in the reciprocal cross. The hybrid lacking the alternative pathway also outperformed the reciprocal cross in terms of total dry matter and seed production. Increased branching with CO2 enrichment was observed in the hybrid lacking the pathway, while branching in the reciprocal cross was only slightly stimulated. These results suggest that alternative respiration consumes luxury carbohydrate and that respiration via this pathway may be considered energetically wasteful in terms of whole-plant carbon budgets. PMID- 3095830 TI - Modulation of epidermal growth factor receptors by human alpha interferon. AB - Treatment of Madin-Darby bovine kidney (MDBK) cells with human interferon (IFN) alpha 2 at 37 degrees C results in a dose-dependent inhibition of cell growth and a reduction of the subsequent binding of 125I-labeled epidermal growth factor (EGF) at 4 degrees C. Human IFN-beta and -gamma, which exhibit little antiviral and antiproliferative activities on MDBK cells, have little effect on cell growth or the binding of 125I-labeled EGF to these cells. The binding of EGF is decreased after exposure to IFN-alpha for greater than 8 hr. Scatchard analyses of the EGF binding data indicate that a 20-hr exposure period results in a decrease in the apparent number of cell-surface EGF receptors and a reduction in the affinity of EGF for its receptor. The rate of internalization of EGF by MDBK cells does not appear to be affected by IFN treatment. PMID- 3095831 TI - Genetic construction, expression, and melanoma-selective cytotoxicity of a diphtheria toxin-related alpha-melanocyte-stimulating hormone fusion protein. AB - The structural gene for diphtheria toxin, tox, has been modified at its Sph I site by the introduction of an oligonucleotide linker encoding a unique Pst I restriction endonuclease site and a synthetic oligonucleotide encoding alpha melanocyte-stimulating hormone (alpha-MSH). The resulting fusion gene directs the expression of a diphtheria toxin-related alpha-MSH hybrid protein in which the diphtheria toxin receptor-binding domain has been replaced with alpha-MSH sequences. The chimeric toxin has been partially purified from periplasmic extracts of recombinant Escherichia coli K-12 and has been found to be selectively toxic for alpha-MSH receptor-positive human malignant melanoma NEL-M1 cells in vitro. PMID- 3095832 TI - Fine specificity, idiotypy, and nature of cloned heavy-chain variable region genes of murine monoclonal rheumatoid factor antibodies. AB - We investigated the immunochemical and molecular characteristics of murine monoclonal rheumatoid factors. Study of the fine specificity of 20 monoclonal rheumatoid factor antibodies shows a wide degree of heterogeneity. However, many express an interstrain cross-reactive idiotype. We show that our rheumatoid factors utilize a restricted set of the heavy-chain variable region (VH) repertoire representing the more 3' VH families. Preferential expression of 3' VH families is known to occur early in development. We report the nucleotide sequence of two cloned rheumatoid factor VH genes, Y19-10 (VH J558) and 129-48 (VH 7183) in which no major differences are observed between VH genes encoding the heavy chain of autoantibodies and antibodies against foreign antigens. PMID- 3095833 TI - Synergism in the activation of human CD8 T cells by cross-linking the T-cell receptor complex with the CD8 differentiation antigen. AB - Resting human T cells can be activated and induced to proliferate by cross linking the T-cell receptor complex (Ti/CD3) with anti-CD3 (T3) antibodies, such as OKT3, together with interleukin 2. Here we describe functional properties of another monoclonal anti-CD3 antibody (BMA 030) that, cross-linked in various ways, only weakly stimulates accessory-cell-depleted T-cell cultures. However, when cross-linked to anti-CD4 or anti-CD8 antibodies a markedly enhanced proliferation of the corresponding subpopulation is observed. We have concentrated on the analysis of CD8 cells and have found that BMA 030, when cross linked together with anti-CD8 (T811), induced proliferation more than 100-fold greater than BMA 030 alone, whereas cross-linking with antibodies to other T-cell membrane antigens (HLA-A, B, or CD5) provided no or marginal synergistic signals. There was no synergistic effect when only one of the two antibodies, BMA 030 or T811, was cross-linked and the other was applied in soluble form. In contrast, each of the two antibodies alone, when applied in soluble form, inhibited activation induced by the cross-linked antibodies. The T-cell differentiation antigen CD8 has been implicated in the major histocompatibility complex (MHC) class I restricted specificity of CD8 T cells. In previous work from other laboratories only the negative influences of soluble anti-CD8 antibodies have been noted. In contrast, our results suggest that cross-linking between Ti/CD3 and CD8 may be a critical event in the activation of mature CD8 cells. We hypothesize that, in antigen-induced T-cell activation, CD8 and Ti/CD3 become cross-linked by their simultaneous binding to class I-associated structures. Such a mechanism, if required for proliferation in early T-cell ontogeny, could generate a selective pressure for CD8 cells to recognize class I-associated antigens. PMID- 3095834 TI - Genetic basis for the cross-reactive idiotypes on the light chains of human IgM anti-IgG autoantibodies. AB - The role of immunoglobulin structural genes in the generation of autoantibodies in humans has not been elucidated. Human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated people often share idiotypic antigens. Antibodies against synthetic peptides have localized two of the shared idiotypic determinants to the second and third complementarity-determining regions of the kappa light chain. The reported sequences of several human RF light chains are remarkably homologous in these regions. Animal studies have shown that some shared idiotypic antigens represent serological markers for immunoglobulin variable (V)-region genes. Therefore, we hypothesized that human RF light chains derived from a single germ-line gene, designated V kappa-(RF), or from a small family of very closely related genes. In the present experiments, we have isolated and sequenced two human V kappa germ-line genes that encode kappa light chains, which are identical or closely related to the light chains of human RF. The data indicate that the shared idiotypic antigens on RF are phenotypic markers for a kappa V-region gene that is highly conserved in the human population. The results also imply that the light chains of IgM anti-IgG autoantibodies can be encoded by germ-line genes without any somatic mutation. PMID- 3095835 TI - Sexual mimicry regulates the attractiveness of mated Drosophila melanogaster females. AB - During mating, male Drosophila melanogaster transfer to the female's cuticle a compound (7-tricosene) that is almost absent from virgin females but is the major hydrocarbon component of the male's cuticle. During the first 3 hr after mating, the amount of 7-tricosene on a female decreases sharply but remains significantly above virgin levels. By 6 hr after mating, female synthesis of 7-tricosene has increased, and females release it when they are exposed to courting males. Transfer of 7-tricosene to immature virgin females by courting males significantly decreases their attractiveness, so 7-tricosene has demonstrable antiaphrodisiac properties. Thus, mated D. melanogaster females appear to mimic males by releasing, during courtship, an antiasphrodisiac pheromone that is almost absent from virgin females but is the most prominent hydrocarbon of the male cuticle. PMID- 3095837 TI - Tissue-specific and constitutive alpha-tubulin genes of Drosophila melanogaster code for structurally distinct proteins. AB - We have determined the nucleotide sequences of all four Drosophila alpha-tubulin genes (alpha 1, alpha 2, alpha 3, and alpha 4). Two of the genes, alpha 1 and alpha 3, are constitutively expressed and code for proteins that are very similar to previously sequenced alpha-tubulins. They differ from each other by only two amino acid substitutions. These two genes also have blocks of homology between the noncoding leader regions of their transcription units. In contrast to these constitutive genes, the tissue-specific alpha 2 and alpha 4 genes code for tubulins with different structures. The alpha 2 mRNA is male-specific in adults and codes for a tubulin that differs from alpha 1 at 21 of the 450 residues. Six nonconservative substitutions are clustered within the 14 carboxyl-terminal amino acids, a region implicated in the regulation of microtubule assembly. The alpha 4 mRNA is maternal and is found only in ovarian nurse cells, eggs, and early embryos. It codes for the most highly divergent alpha-tubulin yet reported and differs from alpha 1 at 149 positions. PMID- 3095836 TI - Structure, evolution, and polymorphisms of the human apolipoprotein A4 gene (APOA4). AB - The genes coding for three proteins of the plasma lipid transport system- apolipoproteins A1 (APOA1), C3 (APOC3), and A4 (APOA4)--are closely linked and tandemly organized on the long arm of human chromosome 11. In this study the human APOA4 gene has been isolated and characterized. In contrast to APOA1 and APOC3 genes, which contain three introns, the APOA4 gene contains only two. An intron interrupting the 5' noncoding region of the APOA1 and APOC3 mRNAs is absent from the corresponding position of the APOA4 mRNA. However, similar to APOA1 and APOC3 genes, the introns of the APOA4 gene separate nucleotide sequences coding for the signal peptide and the amphipathic domains in APOA4. These results suggest that the APOA1, APOC3, and APOA4 genes were derived from a common evolutionary ancestor and indicate that during evolution the APOA4 gene lost one of its ancestral introns. Two restriction endonuclease sites, an Xba I located in the second intron of the APOA4 gene and a different Xba I located 9 kilobases 3' to the APOA4 gene, are polymorphic in Mediterranean and Northern European populations. Haplotype analysis indicated that even though these polymorphic sites are located within 9 kilobases they do not display significant nonrandom association. Finally, restriction mapping analysis of DNA from a patient with combined APOA1-APOC3 deficiency and premature coronary artery disease indicated that this patient has a structurally normal APOA4 gene. PMID- 3095838 TI - Cell-type-specific transcription of an immunoglobulin kappa light chain gene in vitro. AB - We have established a cell-free system, derived from a human B-cell lymphoma, in which immunoglobulin kappa light chain gene promoters are both accurately transcribed and regulated in a cell-type-specific manner. Thus, accurate transcription from the T1 kappa light chain gene promoter was much more efficient in B-cell extracts than in HeLa cell extracts, whereas control promoters (adenovirus major late and histone H2B) were transcribed equally well in either extract. More important, the increased kappa light chain gene transcription in B cell extracts was dependent upon upstream sequences (containing the conserved decanucleotide element) previously shown to be necessary for B-cell-specific transcription in vivo; in contrast, removal of these sequences had no effect on the low level of kappa transcription in HeLa extracts. The maximal level of upstream sequence-mediated transcription was dependent upon template topology. These studies show that there is at least one B-cell-specific factor that stimulates transcription from purified DNA templates, and they further suggest that the in vivo action of the factor(s) on other components of the transcription machinery is direct rather than indirect (e.g., via the maintenance of an open chromatin structure). The cell-free system described here should facilitate both purification and functional studies of the B-cell-specific factor(s). PMID- 3095839 TI - Photocrosslinking of the signal sequence of nascent preprolactin to the 54 kilodalton polypeptide of the signal recognition particle. AB - Photoreactive moieties were incorporated into nascent polypeptides in a wheat germ protein-synthesizing system by using a plasmid-derived preprolactin mRNA and a Lys-tRNA analog, N epsilon-(5-azido-2-nitrobenzoyl)-Lys-tRNA (epsilon ANB-Lys tRNA). The presence of the abnormally large amino acid side chains in the nascent chains did not impair function: complete preprolactin chains were synthesized in the absence of the signal recognition particle (SRP), elongation was arrested in the presence of SRP, and SRP-dependent translocation across the membrane of the endoplasmic reticulum and signal peptidase cleavage were observed in the presence of salt-extracted microsomes. Photolysis of elongation-arrested ribosomes resulted in several light- and epsilon ANB-Lys-tRNA-dependent crosslinks. By using antibodies specific for each of the proteins, one covalent complex was shown to be a photocrosslink between the preprolactin nascent chain and the 54 kDa protein subunit of SRP. This demonstrates that the N-terminal end of a secretory protein is located adjacent to the SRP in elongation-arrested ribosomes and strongly suggests that the signal sequence is recognized by and binds to the 54-kDa subunit of SRP. The other photocrosslinks involve as-yet-unidentified proteins in the large ribosomal subunit, indicating that this method of incorporating probes provides a powerful approach to examining the environment and interactions of the nascent chain during translation and translocation across the membrane of the endoplasmic reticulum. The Lys-tRNA analog also successfully photoaffinity-labeled the Escherichia coli elongation factor Tu (EF-Tu) in the epsilon ANB-Lys-tRNA.EF-Tu.GTP ternary complex. PMID- 3095840 TI - Genes for synapsin I, a neuronal phosphoprotein, map to conserved regions of human and murine X chromosomes. AB - Synapsin I is a neuron-specific phosphoprotein associated with the membranes of small synaptic vesicles. Its function is not entirely clear, but evidence points to a possible role in the regulation of neurotransmitter release. Its biosynthesis is under developmental control. Assignment of the human synapsin I gene to the X chromosome at band Xp11 was accomplished by in situ hybridization, using a rat cDNA probe. Southern blot analysis of DNAs from a panel of human Chinese hamster somatic cell hybrids with defined regions of the human X chromosome confirmed the in situ mapping data. The mouse synapsin I gene was assigned to the X chromosome, proximal to band XD, by Southern blot analysis of Chinese hamster-mouse somatic cell hybrids with normal or rearranged mouse X chromosomes. In situ chromosomal hybridization experiments localized the mouse synapsin I gene more precisely to bands XA1----A4. These results add to the comparative gene map of mammalian species and support certain hypotheses regarding the evolutionary relationship between human and mouse X chromosomes. We hypothesize that the synapsin I gene could be mutated in human X-linked disorders with primary neuronal degeneration, such as the Rett syndrome. PMID- 3095841 TI - Mr 26,000 antigen of Schistosoma japonicum recognized by resistant WEHI 129/J mice is a parasite glutathione S-transferase. AB - Mice of the inbred strain 129/J bred at this Institute (WEHI 129/J) are relatively resistant to chronic infection with the parasitic helminth Schistosoma japonicum. In contrast to more permissive mouse strains such as BALB/c, the WEHI 129/J mice are high responders to a Mr 26,000 adult worm antigen designated Sj26. Cloned cDNAs corresponding to Sj26 have been identified in a S. japonicum phage lambda gt11 amp3 expression library, and their nucleotide sequences have been deduced. The predicted amino acid sequence of the antigen specified by these cDNAs shows striking homology with class mu isozymes of mammalian glutathione S transferases (RX:glutathione R-transferase, EC 2.5.1.18). Extracts of adult worms contain glutathione S-transferase activity, and affinity chromatography of enzyme activity on glutathione columns leads to the purification of a Mr 26,000 molecule that comigrates with Sj26. Although vaccination studies in mice with a beta galactosidase-Sj26 fusion protein from Escherichia coli are encouraging, more immunogenic preparations of the antigen are likely to be required to establish the utility of Sj26 as a model vaccine. PMID- 3095842 TI - A repetitive antigen of Plasmodium falciparum that is homologous to heat shock protein 70 of Drosophila melanogaster. AB - We describe an antigen of Plasmodium falciparum, defined by a cDNA clone designated Ag63. The antigen is an abundant, soluble cytoplasmic polypeptide of Mr 75,000 present in all stages of asexual development in the blood and in gametocytes, but not in sporozoites. The sequence of the cDNA clone revealed that, like many other antigens of P. falciparum, it contains tandemly repeated amino acid sequences, in this case Gly-Gly-Met-Pro. However, the rest of the sequence is 70% homologous at the amino acid level to the heat shock protein hsp70 of Drosophila melanogaster. PMID- 3095844 TI - [Nursing care for patients undergoing bone marrow transplantation]. PMID- 3095845 TI - [Bibliographic research: a guide to the use of the International Nursing Index]. PMID- 3095843 TI - The role of the T-cell receptor in thymocyte maturation: effects in vivo of anti receptor antibody. AB - The T-cell receptor, which recognizes antigen plus a product of the major histocompatibility complex, has been postulated to drive T-cell maturation in the thymus by engaging major histocompatibility complex proteins expressed on thymic stromal cells. We tested this idea by injecting neonatal animals with an anti receptor antibody, KJ16, that binds to about 20% of T cells and is capable of blocking receptor function. In the presence of this antibody, mature T cells bearing the KJ16 epitope failed to develop. On the other hand, although the antibody could be shown to bind to receptors on cortical thymocytes, it did not prevent the rapid expansion or survival of the bulk of the KJ16+ cells in this population. These results are consistent with the hypothesis that most cortical thymocytes arise by a receptor-independent mechanism and that only a small proportion of these cells mature by a process dependent on receptor-major histocompatibility complex interactions. PMID- 3095846 TI - [Public health implications of the Chernobyl accident, USSR]. PMID- 3095848 TI - The lipoxins: determination of their biosynthesis. AB - The stereochemistry and double bond geometry of a novel series of leukocyte derived arachidonic acid metabolites, the lipoxins, was determined by comparison to pure unambiguous synthetic standards. The lipoxins were found to be a mixture of four lipoxin A isomers and two lipoxin B isomers. In determining the biosynthesis of these compounds, they were shown to be formed via a tetraene epoxide. In addition, it was shown that all of the lipoxin isomers formed by the incubation of 15-HPETE with human leukocytes were also formed by non enzymatic hydrolysis of this tetraene epoxide. PMID- 3095847 TI - Investigation of the actions of the benzodiazepine antagonists Ro 15-1788 and CGS 8216 using the schedule-controlled behavior of rats. AB - Ro 15-1788 and CGS 8216 antagonise many of the pharmacological effects of benzodiazepines but both of these compounds have also been shown to exert behavioral effects when administered alone. In the present study the effects of Ro 15-1788 and CGS 8216, alone and in combination with diazepam and with the benzodiazepine receptor ligand zolpidem, were investigated. Diazepam and zolpidem produced dose-related decreases in rates of food-reinforced lever-pressing maintained by a fixed-ratio (FR 10) schedule. CGS 8216 also reduced response rates although Ro 15-1788, at several doses, produced small, but statistically significant, increases in responding. When the diazepam and zolpidem dose response curves were re-established in the presence of a dose of Ro 15-1788 or CGS 8216 the depressant effects of the higher doses were antagonised. However, neither diazepam nor zolpidem blocked the rate reducing effect of CGS 8216 which may not therefore be due to an action at benzodiazepine receptors. PMID- 3095850 TI - Platelet-activating factor-induced vasoconstriction in rat isolated, perfused hearts: contribution of cyclo-oxygenase and lipoxygenase arachidonic acid metabolites. AB - The mechanism of the coronary vasoconstrictor action of platelet-activating factor (PAF) has been investigated in rat isolated, perfused hearts. PAF elicited an increase in coronary perfusion pressure which was attenuated by indomethacin- or diethylcarbamazine- pretreatment, whereas FPL55712 had a marked inhibitory effect. Accompanying the coronary vasoconstrictor response to PAF was an increase in the release of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TxB2 and the appearance of biologically-active concentrations of LTB4 and LTC4 in the cardiac effluent. Indomethacin-pretreatment prevented the increase in release of the measured cyclo oxygenase metabolites without significantly altering the generation of either LTB4 or LTC4. Diethylcarbamazine markedly inhibited the PAF-induced release of both cyclo-oxygenase and lipoxygenase products. These findings suggest a causal role for vasoconstrictor arachidonic acid metabolites in the acute cardiac effects of PAF with the quantitatively most important contribution to the vasoconstriction made by LTC4. PMID- 3095849 TI - Inhibitory effects of a novel platelet activating factor (PAF) antagonist (BN 52021) on antigen-induced prostaglandin and thromboxane formation by the guinea pig lung. AB - The effects of a new Platelet-Activating Factor (PAF-acether) antagonist (BN 52021) extracted from Ginkgo biloba leaves have been studied on the release of metabolites of arachidonic acid in IgG-dependent guinea pig pulmonary anaphylaxis in vitro. Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) were assayed using a novel ELISA technique. The release of PGE2 and TxB2 from anaphylactic lungs reached a maximum 4-5 min following the antigen challenge (about 3.2 and 31.0 ng/ml respectively) and decayed slowly during the following 25 min. BN 52021 (1, 3 and 30 micrograms/ml) produced dose-dependent decreases of the release of PGE2 and TxB2. These results suggest that there are some interactions between the release of icosanoids and PAF-acether in anaphylaxis. PMID- 3095851 TI - Alkylacetylglycerols versus lyso-PAF as precursors in PAF biosynthesis and the role of arachidonic acid in PAF metabolism. PMID- 3095852 TI - Acylation of 1-alkyl- and 1-acyl-lysophospholipids by rat platelets. PMID- 3095853 TI - Syntheses and in vitro antimicrobial evaluation of some benzimidazol-2 ylmethylthioureas, benzimidazol-2-ylacetylthiosemicarbazides and products of their condensation with monochloroacetic acid. AB - N-Benzimidazol-2-ylacetyl-N'-[alkyl- and arylthio (carbamoyl)]hydrazines and N benzimidazol-2-ylmethyl-N'-alkyl- and -arylthioureas were subjected to condensation with monochloroacetic acid to afford N-benzimidazol-2-ylacetyl-N' 2,3, 4,5-tetrahydro-4-oxo-3-alkyl- and -arylthiazol-2-ylidenehydrazines and 3 benzimidazol-2-ylmethyl-2-alkyl- and arylimino-2,3-dihydrothiazol-4-(5H)ones, respectively. In preliminary antimicrobial testing, some compounds turned out to have significant activity against Staphylococcus aureus. PMID- 3095854 TI - A three-zone model of soft-tissue damage by a CO2 laser. AB - CO2 laser damage to soft tissue may be divided into three zones--an outer layer of carbonised material, a zone of vacuolation where cavities have been formed by the explosive conversion of water to steam and a coagulated zone which has been formed at temperatures below 100 degrees C. A model is proposed which predicts the maximum (i.e. dynamic equilibrium) depths of each of these layers. The maximum effective thickness of the vacuolated zone is shown to depend upon the absorption coefficient of the tissue for CO2 laser radiation, but not on the incident irradiance. The thickness of the carbonised zone is shown to decrease with increasing irradiance, and the depth of the sub-boiling coagulated zone also decreases with increasing irradiance, but depends to some extent on the penetration of laser radiation through the soft tissue. Redistribution of heat within these zones after extinction of the laser radiation is considered, as is the effect of pulsed laser radiation. The predictions of the model could be tested by suitable experiments. PMID- 3095855 TI - Computer-based solution to a clinical education problem in a physical therapy course. AB - This article describes the solution to a logistical problem involving the assignment of multiple clinical experiences to students in an undergraduate physical therapy course. Physical therapy faculty members collaborated with a computer programmer to formulate a computer program that would satisfy the organizational needs imposed by this problem. We suggest that the skills of the physical therapist combined with those of a computer programmer can be used to generate effective, computer-based solutions to many other problems related to the organization of data and to decision making in physical therapy. PMID- 3095856 TI - Observations on the photosensitized breakage of DNA by 2-thiouracil and 334-nm ultraviolet radiation. PMID- 3095857 TI - Photoreactivating enzyme from Streptomyces griseus--VI. Action spectrum and kinetics of photoreactivation. PMID- 3095858 TI - Experimental research of the influence of the body electrolytic composition on the toxic effect of morphine. AB - The ionic composition of the internal environment influences the toxic effect of morphine. LD50 for morphine and thiopental was tested in 3 lots of mice: with sodium depletion, with sodium load, and with normal sodium content in the food. LD50 for morphine was clearly influenced by the treatment received by the animals. Since such differences could not be found with thiopental, we consider that the ionic composition of the internal environment could modify the steric conformation of the receptor-macromolecule for opioids. PMID- 3095859 TI - [Transcapillary transport of macromolecules in streptozocin diabetes in rats]. PMID- 3095860 TI - The influence of auditory and lithium stimulation on blood and brain serotonin in the normal rat and in that susceptible to audiogenic convulsions. AB - Investigations were carried out in two groups of male rats: a group susceptible to audiogenic convulsions and a control group. The following parameters were determined under basal conditions and 24 and 48 hours after intraperitoneal administration of a single lithium carbonate dose (0.67 mEq/animal), before and after auditory stimulation: serotonin content in the blood and brain tissue (separately from the hypothalamus, rhinencephalon, midbrain and sensory-motor cerebral cortex) by fluorimetry: water-saline retention, renal potassium elimination, the dynamics of renal lithium elimination. The results showed that in the rats prone to audiogenic convulsions, blood serotonin concentrations are twice those in the controls, whereas serotonin levels in the brain are lower than in the controls. The administration of lithium is followed by a decrease in blood serotonin in the animals with audiogenic convulsions but does not influence the serotonin content in the brain. Acoustic stimulation does not influence the behaviour of the controls but induces convulsions in the animals sensitive to noise. After auditory stimulation under basal conditions or 48 hours after the administration of lithium a decrease takes place in cerebral serotonin and an increase in blood serotonin in the controls whereas in the rats sensitive to noise, cerebral serotonin increases and blood serotonin decreases on stimulation under basal conditions due to the convulsions and metabolic alterations induced by the latter. These findings suggest the existence of different mechanisms for the transport of serotonin in the blood of rats prone to audiogenic convulsions. These mechanisms may be influenced either by acid catabolites resulting from convulsive activity or by the administration of lithium. The latter may induce persistent alterations in the blood transporter, as appears to result from the observation at 48 hours after the administration of lithium. PMID- 3095861 TI - [Changes of the shape of the QRSH loop in old anterior myocardial infarction]. PMID- 3095862 TI - Vagal involvement in sinus arrhythmia attenuation under mental load. AB - Experimental data document the slight increase of heart rate found during mildly stressing mental load as not being sufficient to explain concomitant sinus arrhythmia attenuation by pure sympathetic reaction. A general outlook on autonomic regulation and more specific direct and indirect arguments show heart rate response to mental load as underlain by a higher level balance of sympathetic and vagal drives. Their competition results mostly in slight increase yet sometimes in preservation or decrease of mean HR, while the consistency of sinus arrhythmia attenuation remains to reflect vagal increase specifically connected to cortex activation. PMID- 3095863 TI - Peripheral lymphocyte subpopulations changes during labor. AB - Peripheral circulating E-rosette-forming cells subpopulations (high affinity and low affinity E--RFC) were studied in pregnant women. In prelabor the high affinity/low affinity E--RFC ratio was found to decrease as compared with the controls by the decrease of the high affinity E--RFC (mean +/- SD, 33.4 +/- 15.9%, p less than 0.01) and the increase of the low affinity E--RFC percentage (mean +/- SD, 37.0 +/- 11.8%, p less than 0.001). As compared with prelabor the low affinity E--RFC subpopulation decreased during normal labor (mean +/- SD, 14.1 +/- 6.2%, p less than 0.001) and not in abnormal labor. These changes might be implicated in the final "fetal allograft rejection" and are probably due to some serum factors in pregnancy. PMID- 3095864 TI - The distribution of codons by classes of triplets in the sequence of genes. AB - According to a criterion of symmetry-asymmetry, the triplets of the genetic code can be divided into four classes. In the genes of viruses and human mitochondria, the frequency by which a codon is followed by a codon of the same class is higher than that theoretically estimated. This is the consequence of the fact that in an initial stage of evolution many codons were duplicated. PMID- 3095865 TI - The "involuntary postcontraction" mechanism or the postcontractile elastic restitution. AB - Unquestionable experimental proofs are brought forward in support of the non cortical origin of "involuntary postcontraction". The mechanism of this phenomenon is purely passive and it originates in the elastic component of the muscular organ. Far from inducing the postcontractile event, cortical induction brakes it. The results obtained up to now enable the authors to consider that the analysis of postcontraction provides quantifiable information of great practical importance on the type and momental functional state of human nervous system. PMID- 3095866 TI - Effect of amino acid imbalance and deficiency on dietary choice patterns of rats. AB - Detailed dietary choice patterns were determined with a computerized feeding monitoring system in groups of Sprague Dawley rats kept on a 12:12 hr light-dark cycle and offered in sequence a series of dietary choice regimens involving amino acid-imbalanced or deficient diets with threonine as the most limiting amino acid. Animals established their preference for a threonine-basal diet over a threonine-imbalanced or a threonine-devoid (devoid of threonine) diet shortly (within 2-3 hr) after the consumption of small quantities of either diet in the beginning of the first dark-cycle. An intensive sampling process characterized by frequent small bouts was evident throughout the light period. Both the meal size and the meal frequency of the imbalanced or devoid diet were curtailed after prolonged choices. Animals preferred the threonine-corrected (imbalance corrected by threonine supplementation) over the threonine-basal diet initially with an increase in meal frequency. But no clear choice for either diet was observed thereafter. Animals did not establish their preference for the threonine corrected diet when paired with the threonine-devoid diet until after 5 days with a steady decrease in the meal size of the devoid diet but not the meal frequency. When the protein-free diet was introduced as an alternative for the threonine imbalanced diet, animals selected the protein-free diet during the first dark cycle after consuming a small amount of the imbalanced diet. Initially there was a drastic reduction in meal size of the imbalanced diet and subsequently a decrease in meal frequency as well. Nevertheless, animals immediately rejected the protein-free diet and chose the threonine-basal diet when it replaced the imbalanced diet as an alternative. The almost exclusive preference for the basal diet occurred in the beginning of the first dark-cycle with an increase in meal size but no change in meal frequency. The sampling bouts of small quantities, which followed the first introduction of the diets in the choice regimens, may be an inherent investigative behavior whereby the physical or oropharyngeal properties of the diets are recognized. The establishment of the choices for the alternative diets in the present experiments provides additional information about the rapid time course of the food intake control mechanisms in rats fed amino acid-imbalanced or deficient diets. PMID- 3095867 TI - Possible cytoskeletal association of 69,000- and 68,000-dalton heat shock proteins and structural relations among heat shock proteins in murine mastocytoma cells. AB - When murine mastocytoma cells (FMA 1) were heat shocked (42 degrees C for 4 h), nine heat shock proteins (HSPs) were detected by two-dimensional gel electrophoresis. Their apparent molecular weights were 100, 85, 69, 68, 32, 30, and 23 kDa (3 of 23 kDa). The structural homology of 4, 69, 68, 32, and 30 kDa, was demonstrated by two-dimensional tryptic peptide mapping. The 69- and 68-kDa HSPs were purified and rabbit antisera against these HSPs were prepared. A small fraction (less than 10%) of the 69- and 68-kDa HSPs were copurified with the microtubules and were present in the Triton X-100/KCl cytoskeletal fraction as shown by immunoblotting with the antiserum and by peptide mapping. Our results are consistent with the hypothesis of a cytoskeletal role for HSPs. PMID- 3095868 TI - Historical aspects of pediatric surgery. PMID- 3095869 TI - The history of pediatric surgery in Germany. AB - Pediatric surgery as defined today is a very young specialty, and it was not until the middle of our century that pediatric units were established at surgical clinics in Germany. Pediatric surgery in Germany developed first in children's hospitals. The author distinguishes four stages: Stage 1: The pediatrician as operating surgeon; Stage 2: The surgeon as consultant; Stage 3: Pediatric surgical hospitals at children's hospitals; Stage 4: Pediatric surgery as an independent discipline in its own right. This chapter then relates the history of the German Society of Pediatric Surgery and the coming of age of pediatric surgery as a completely independent discipline, in which there are now 55 pediatric surgical units in the Federal Republic of Germany. The publications, textbooks, and journals listed at the end of this chapter show the advance of this discipline. PMID- 3095870 TI - The history of oesophageal atresia and tracheo-oesophageal fistula--1670-1984. AB - The history of oesophageal atresia commenced in the year 1670 with Durston's description of "A narrative of a monstrous birth at Plymouth". However, the most significant contribution in the 17th century was made by Gibson, who clearly described the clinical picture and necropsy findings in a baby with a proximal oesophageal atresia and a distal tracheo-oesophageal fistula. The 18th century was singularly lacking in contributions to the literature, but there were many important presentations during the 19th century. Early in that century Martin in France and Hill in United States of America contributed to the literature; subsequently, many anecdotal references can be found particularly in England, and ultimately a surgical attempt to correct the anomaly was made in 1888 by Steele in London. With this, the pre-surgical era gave way to the surgical era, and at a later stage pre-survival era was to give way to the survival phase. Reference will be made in the text to these various phases in the history and to the many pioneering surgical endeavours which took place in the earlier years of the 20th century. It will be seen that the surgical efforts employed palliative procedures, indirect attacks on the problem and finally direct attacks. The classic successes by indirect methods which were achieved by Ladd and Leven in babies born in 1939 were to be followed by the first successful end-to-end anastomosis which was achieved in Ann Arbor, Michigan, by Cameron Haight. Others had attempted primary anastomosis, and Lanman in particular deserves mention. However, it was Cameron Haight who opened a new era in the history of the treatment of oesophageal atresia; the recent history is largely concerned with increasing experience and refinements in technique. For the future historian many pathways can still be explored, including oesophageal replacement, the unstable trachea, follow-up studies and research projects. This history also included comments on the history of the less frequently encountered anomalies and such aspects as classification and radiology. The history of oesophageal atresia and tracheo-oesophageal fistula is a mini history of surgery - "oesophageal atresia is the epitome of modern surgery". PMID- 3095871 TI - Historical aspects of hydrocephalus. AB - From early days on physicians took interest in hydrocephaly because of its grotesque appearance. Already Hippocrates recommended decompression-trepanation for the treatment of hydrocephalus. Only since anatomy and pathophysiology of hydrocephalus as well as production and absorption of the cerebrospinal fluid was clarified, more effective operative techniques could be developed. Conservative treatment was unsuccessful or was useful only as temporary or adjuvant therapy supporting surgical procedures. A great variety of operative methods was described since the middle of 19th century which yielded, however, unsatisfactory results in most instances. Results improved since the introduction of effective valve systems in combination with ventriculoatrial and ventriculoperitoneal shunts. Despite of improved results, the treatment of hydrocephalus remains problematic as is shown by the still high complication rate and the restless search for more effective ways of treatment. PMID- 3095872 TI - 100 years of pediatric surgery in Stockholm, with personal memories from the last 50 years. AB - The first children's hospital in Sweden (Kronprinsessan Lovisa's Children's Hospital) was established in Stockholm in 1854. In 1885 it was divided into a medical and a surgical department. This constituted the birth of pediatric surgery in Sweden. Pediatric surgery has been included in undergraduate teaching programs since 1945. A personal Associate Professorate in Pediatric Urology was instituted at the Karolinska Medical School in Stockholm for N. O. Ericsson in the late fifties. Upon his retirement in 1976 this personal chair was converted into an established Professorship in Pediatric Surgery. Pediatric surgery has been recognized as a specialty by our Medical Association since 1947. A survey of the Annual Reports from the Lovisa Hospital from 1885 to 1969 shows three phases in the development of our specialty in Sweden. The first stage extends from 1885 to 1932. During this period the disease pattern was dominated by septic and tuberculous infections, by empyemas, and by ENT diseases. Few cases of congenital malformations were reported. The bulk of general surgery in childhood was performed in the departments of general surgery. The second stage (1932-1945) was characterized by a decreasing incidence of tuberculous infections, by a successive transfer of orthopedic and ENT patients to the Departments of Orthopedic and ENT surgery respectively. During this period, a marked increase occurred in the volume of malformation surgery. This was due to the centralized treatment of congenital anomalies. The third stage started in 1945. The war had ended and we became acquainted with the dramatic development of pediatric surgery in other countries, in particular in the USA. The main advance was the possibility of opening the chest for repair of congenital anomalies of the heart and the great vessels, of the esophagus, and of the diaphragm. Soon afterwards, rectosigmoidectomy was introduced for the treatment of Hirschsprung's disease. In 1952, a second department of pediatric surgery was opened in Stockholm as a part of a new Children's Clinic at the Karolinska University Hospital. The major part of general surgery from the Stockholm area and all of the cardiovascular surgery stayed with the "Lovisa Hospital", while the major part of neonatal surgery and specific abdominal surgery was performed at the Karolinska Hospital. In order to improve the rather underdeveloped situation of pediatric urology, N. O. Ericsson was appointed to the post of Associate Head of the Karolinska Department, soon bringing this field to the frontlines of international standards. This historical review ends with some of the author's personal memories from the last 50 years. PMID- 3095873 TI - The history of colostomy in childhood. AB - The idea of performing a colostomy in a child was first brought up by Littre in 1710. It lasted, however, 50 years until the first successful operation was published. Especially in the 19th century various ways to approach the colon have been practiced with frequently disappointing results (lumbar, inguinal approach). Only at the end of the century, colostomy was used as a guide for a pull-through operation. With improved surgical and anaesthesiological techniques, colostomy has gained more importance as a temporary measure in order to postpone definitive surgery. Various new techniques have been developed within the same time. In our days, colostomy is a safe procedure and has a more defined place in handling children with imperforate anus and Hirschsprung's disease. PMID- 3095874 TI - Hirschsprung's disease: an historical review. AB - A historical review of Hirschsprung's disease is of relevance for several reasons. The historical events are revealing as to how clinical diseases are often slowly unravelled. In addition, many unsolved problems are highlighted. Firstly the exact cause is unknown. There is obviously an interaction between genetic and environmental factors, the nature of which is of interest to basic scientists as well as clinicians. Secondly the pathophysiological explanation for the functional obstruction, and especially its variability, is still incomplete. Much more needs to be known about normal gastrointestinal physiology before this question can be fully answered. Thirdly the technique and timing of operative correction remains inconclusive. Despite extensive postoperative assessment there is no one operation that is clear superior. Each have characteristic problems, but all share the main problem; the abnormal internal sphincter. It remains uncertain how much (if any) of the sphincter should be bypassed. As well the optimal timing of operation is uncertain, with some theoretical advantages being suggested for earlier operation. However, these advantages need to be balanced against possible technical problems. Nevertheless the aim of surgical correction should be the full attainment of normal faecal continence. PMID- 3095875 TI - Club-foot through the centuries. AB - This is a study of the history of club-foot from ancient times up to the present. It embraces not only the clinical aspects of the deformity but also its social implications, particularly of its early history when the attitude of society towards the lame and crippled in general and to foot deformities in particular is discussed. Relevant references from Greek mythology and also from the Old Testament are quoted. A close study is made of the old Chinese custom of foot binding which produced club-foot like deformities which became a symbol of social standing. Inevitably, like most other medical conditions, club-foot has been well described by Hippocrates and it is a sobering thought that his concepts of causation and his principles of treatment are as valid today as they were 2300 years ago. This paper also briefly describes club-foot in history and art. Encouraged by society's compassionate approach towards the cripple, famous painters of the 17th century produced sympathetic portraits of the deformed and the club-footed. Well-known personalities who suffered from club-foot, such as Lord Byron and Sir Walter Scott, are mentioned and it is shown how the deformity affected them. The saga of the physician and surgeon W.J. Little, himself afflicted by club-foot, is unfolded. His life was dedicated to the study and relief of his own deformity and later he devoted his efforts towards the cure of his fellow sufferers. W.J. Little has done so much for the advancement of orthopaedic surgery that Sir Robert Jones called him the father of orthopaedic surgery; yet at heart W.J. Little was a physician! Another physician, Nicholas Andre, deserves the title of father of orthopaedic surgery. He coined the word 'orthopaedia' and laid down the principles of preventing and correcting deformities and he detailed the conservative management of club-foot. The treatment of the deformity came into the hands of bone setters and instrument makers and it was almost beneath the dignity of a surgeon to treat it. Yet, with the advent of tenotomy, popularised by Little, surgical treatment of the condition increased, aided by the development of antiseptic and aseptic technique and anaesthesia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3095876 TI - The history of treatment of cleft lip and palate. AB - The history of surgery of cleft lip and palates reaches as far backwards as the prechristian era to 390 B.C. when for the first time a cleft lip was closed successfully in China. Although Egyptian and Greek medicines developed to a remarkable degree, no descriptions of cleft operations have survived. In the middle ages operations on cleft lip have been several times described. A successful operation on a cleft palate did however not occur until 1816. This can be explained by the fact that cleft palates were thought to be secondary to syphilis, but also because without anaesthetic this operation was extremely painful and difficult. Graefe in 1816 [20a] and Roux in 1819 [49] published the first satisfactory results. After the introduction of chloroform cleft surgery made remarkable progress. The development of cleft surgery has been chronologically described and finally the present state of affairs is discussed. PMID- 3095877 TI - Professor Bochdalek and his hernia: then and now. AB - An account is given of Professor V.A. Bochdalek's life, and special consideration is given to his work on the pathological anatomy of the diaphragmatic hernia which bears his name. The development of the management of congenital diaphragmatic hernias since 1946, when Robert Gross performed the first successful operation on this condition, is briefly outlined. PMID- 3095878 TI - Paediatric urology 1000 years ago. AB - In this paper we present a commentary on four books from the paediatric urology point of view; al-Hawi (Continens), R. fi Siyasat as-Sibyan wa tadbirihim, at Tasrif and al-Qanun by the Moslem scholars ar-Razi, Ibn al-Jazzar, al Zahrawi and Ibn Sina who lived within the period of the ninth to the eleventh centuries. In these books the supreme abilities of the authors as clinicians and their role in the creation of clinical medicine are shown by: The presentation of the various pathological conditions usually starting with the complaint then describing the origin of the disease and enumerating the accurate signs necessary for diagnosis. Differential diagnosis between various conditions which produce similar complaints is precisely described. For example, retention of urine and different types of anuria, types of renal haematuria, dormant and moving renal stones and their precise localisation, renal or vesical pain and pain due to colitis. Finally, the methodical classification of the diseases according to the organs affected is discussed. The description of the pathology and the knowledge of new diseases was an important advance made by these scholars. From the urological point of view, spina bifida and its relation to incontinence was first described by ar-Razi and most of the diseases of the kidney and bladder can be recognized in the systemic classification of the diseases of these organs given by Ibn Sina who pointed out the psychological role in some cases of nocturnal enuresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095879 TI - Sketches of surgical cases drawn in 1884-87 at the East London Hospital for Children, Shadwell. AB - Most of the surgical cases were under the care of the Surgeon Robert William Parker, who was on the staff of the East London Hospital for Children, Shadwell. He was born in 1842 and qualified in 1869, and after working at the London Hospital he served with distinction as a volunteer with the Anglo-American Ambulance in the Franco-Prussian War 1870-1871. Then he became Resident Medical Officer at the Children's Hospital, 49 Great Ormond Street, and later in 1876 joined the staff of the Shadwell Hospital and was an active member of several London medical societies at which he presented surgical topics and cases of paediatric interest. Also, having a knowledge of German and French, he translated several surgical works from the continent. This miscellany of sketches drawn by a Nurse Reeve in 1883-1887 consists of the following: first, talipes and genu recurvatum. Each supposed to be caused by their intrauterine position; flexion contractures of the knee and equinus deformity due to poliomyelitis; lesion, such as amniotic band of the fingers, naevus of the forearm and warty lesion of the finger; skin contracture of the wrist following burns; absence of the lower ends of the radiui; two fatal cases of cancrum oris (noma) following measles; one of cleft palate and lip; three drawings of malignant disease of the thigh and face; finally strumous dactylitis and cyst of the neck. PMID- 3095880 TI - The cradle of pediatric surgery. AB - The nearly two hundred years history of the Hopital des Enfants-Malades in Paris is described, with special emphasis on the development of pediatric surgery in this hospital. Described is also the work of the various surgeons-in-chief, who since 1899 were also appointed professors of pediatric surgery. Progress was slow during the first half of the nineteenth century, but after Guersant took over in 1844 the hospital became a center for this specialty. PMID- 3095881 TI - Pediatric surgery in Islamic medicine from the Middle Ages to the Renaissance. AB - Albucasis lived throughout the tenth century, practicing medicine for more than 40 years in Zahra at the outskirts of Cordoba. This was the period of the greatest splendour of Arab domination of Spain. Albucasis taught medicine at the university of Cordoba and published an encyclopedia of medicine comprising 30 volumes, the last one dealing with surgery. This work was translated into all civilized languages and was the standard medical textbook right till the eighteenth century. This paper deals with many pediatric surgical conditions as described in Albucasis' 30th volume. The pathology and treatment of harelip, hydrocephalus, the adenoids, ranula, gynecomastia, imperforated external urinary meatus, circumcision, hermaphrodites, imperforate anus, and supernumerary and webbed finger were all described by Albucasis, and his remarks are discussed here in some detail. PMID- 3095882 TI - William E. Ladd, M.D.: great pioneer of North American pediatric surgery. AB - William E. Ladd (1880-1967) was the great pioneer pediatric surgeon of North America. His family had been New England merchants. He was educated at Harvard and worked within the Harvard Medical School during his entire surgical career. He began to limit his surgical practice to the care of infants and children at the Boston Children's Hospital soon after World War I. One basis for his great contributions lay in the establishment of an accurate medical records system with a thorough follow-up of the patients. Another basic factor was the development of uniform policies and methods for each type of surgical disease. These policies and methods then underwent evolution as potential improvements appeared. Using this general approach, Ladd influenced the improvement in care of almost all of the common types of pediatric disease treatable by surgery. Among the earliest were intussusception and pyloric stenosis. Later, among many other things, he developed useful systems for the treatment of hernias, rectal bleeding, biliary atresia, failure of rotation of the G.I. tract, rectal anomalies, and exstrophy of the bladder. He made unusual contributions to the care of Wilms' tumor and atresia of the esophagus. He was a great teacher. His pupils have become the teachers of many other pediatric surgeons throughout the world. PMID- 3095883 TI - Denis Browne: colleague (1892-1967). AB - The purpose of this character study is not to assess the achievements of this great paediatric surgeon but to describe this extraordinary, adventurous, rebellious and difficult man, his intelligence, intellectual curiosity and intense interest in technical problems, as well as his bluntness of manner which was confusing and irritating to some of his colleagues. Denis Browne is described as a shy and sensitive nature, which made it difficult for him to establish ordinary human relationships, but also as a strangely aloof colleague with a flair for clothes, remarkable skills at riding, shooting, tennis, billiard and golf, and much admired by his juniors. Denis Browne is also described as a demon for work, a man who had the courage of his convictions and acted upon them. Those who understood him admired him to the point of idolatry but he was also considered as the supreme egotist not giving an inch in discussions and overriding many of his colleagues, making enemies of them as he went and then deeming himself greatly wronged by lack of recognition. With a more modest approach he might have had an easy life with his genius acclaimed by everyone, rather than a life of struggle against ignorance and prejudice which, all at the same, he greatly enjoyed. PMID- 3095884 TI - Denis Browne: surgeon. AB - Denis Browne was the first surgeon in England to confine his practice entirely to children. The methods of treatment devised by him were new and often revolutionary and were frequently attacked and criticized, but they worked. He regarded his research into the aetiology of congenital deformities as his most important single scientific contribution. In 1931, he published his first article on talipes equinovarus. He further enlarged his theory of the mechanical origin of congenital deformities in a study published in 1936. The mechanical theory led him to search for treatment by use of selectively applied pressures and controlled movements. He did not like open corrections. When confronted by a surgical problem he would invariably start by studying the anatomy of the region involved. He was the first to describe the superficial inguinal pouch. His anatomical studies eventually enabled him to perfect the operation for inguinal hernia in infancy and childhood and formed the basis of his operation for cleft palate and of his work on the surgical anatomy of the tonsil. He was the first pediatric surgeon to routinely employ transverse abdominal incisions. He preferred immediate anastomosis to the temporary enterostomies. He introduced the end-to-back anastomosis. He helped rationalizing and perfecting the operative technique for pyloric stenosis. Malformations of the perineum were the subject of many studies. His operation for hypospadias is also well known. His other advances in paediatric surgery, such as treatment of various infective conditions and cardiovascular surgery, were at the time original and important. His inventive genius was best seen in his development of numerous instruments and appliances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095885 TI - Robert E. Gross. AB - Born in 1905, Gross graduated with honors from Carleton College and the Harvard Medical School. After spending 2 years in pathology, he entered his surgical training at the Peter Brent Brigham Hospital and at the Boston Children's Hospital with Dr. William E. Ladd, who occupied the first Chair of Pediatric Surgery in the United States. After 3 years of basic training with a wide variety of surgical problems in both adults and children, he decided to devote his considerable talents toward solving some of the problems of children with congenital malformations. After having returned to Harvard to assume the Chief Residency in Surgery at the Boston Children's Hospital, he worked out a surgical approach to the closure of the patent ductus arteriosus, and he performed the first successful ligation of this structure. Two years later, Gross co-authored with Dr. Ladd Abdominal Surgery of Infancy and Childhood. In the laboratory Gross was actively pursuing the treatment of anomalies of the heart and great vessels. With Dr. Charles Hufnagel, he developed a practical method of preserving, sterilizing, and using aortic homografts to bridge damaged aortic areas, and thus introduced modern reconstructive vascular surgery. In 1947 Gross was named Professor of Children's Surgery at Harvard Medical School and Surgeon-in-Chief of the Boston Children's Hospital. His contributions to the literature included the classic textbook Surgery of Infancy and Childhood. Gross was elected President of the American Association for Thoracic Surgery in 1964, and served as the first President of the newly formed American Pediatric Surgical Association in 1970.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095886 TI - Max Grob (1901-1976). AB - Max Grob's first appointment in 1928 was as a first-year resident at the cantonal infants' hospital of his native town, Zurich. He then worked with Monnier in the surgical department of the same hospital and was so fascinated by his task that he decided to devote himself exclusively to paediatric surgery and completed his training with P. Clairmont at the University Hospital of Zurich in 1936. This was followed by a 6-month course in the surgical department directed by L. Ombredanne at the Hopital des Enfants Malades, Paris, where he studied the techniques used in paediatric surgery and in particular in paediatric urology. With Veau, he familiarized himself with the treatment of cleft lip, jaw and palate. Back in Zurich in late 1936, he opened a private practice as a specialist in paediatrics and surgery. Two years later he was elected to be Monnier's successor at the children's hospital. It was wartime, and there was no exchange of experience on an international level. His main interest was in surgical correction of congenital malformations and cardiac surgery. He carried out the first heart operation in a child in Switzerland and was successful. He operated on a wide variety of congenital heart defects and introduced artificial hypothermia. He was the first to use a heart-lung machine and also did pioneering work in the field of surgical treatment of cleft lip, jaw and palate. He was the first surgeon in Switzerland to perform a pull-through operation for Hirschsprung's disease and to undertake correction of a "short oesophagus".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095888 TI - The dawn of paediatric surgery: Johannes Fatio (1649-1691)--his life, his work and his horrible end. AB - Johannes Fatio was probably the first surgeon who systematically studied and treated surgical condition of children. Born in Basle in 1649, he never studied medicine at the university there but became a member of the barber's guild. Later he studied medicine and became a doctor of the University of Valence. He returned to Basle to practice surgery, midwifery and paediatric surgery. He wrote a number of medical books, but only one, The Helvetic Reasonable Midwife, still exists. In it he devotes a whole section to surgical afflictions of children. He describes ingenuous operations for such conditions as hypospadias, hydrocolpos, imperforate anus and many more. He was the first surgeon successfully to separate conjoined twins. He became involved in the turbulent politics of the city of Basle and was largely responsible for the overthrow and modern ratio of the Basle parliament and government. In the following counter-revolution he was captured, imprisoned, tortured and executed. All his written works were destroyed by the authorities; The Helvetic Reasonable Midwife was published 70 years after his death. PMID- 3095887 TI - The history of pediatric surgery in France. AB - In 1741, Nicolas Andry, counsellor of King Louis XV, published a book about "orthopedics," inventing this word. The book is interesting as the author refers to beliefs and habits of the time. In 1864, Guersant published Notes About Pediatric Surgery, a real textbook which was translated into English and German and dealt with the importance of children's psychological training, anesthesia, and water or mother's milk after the operation, and also described tracheotomy, draining of cervical adenitis, and lithotrity. The classification of bone affections was still very confused. Tuberculosis and syphilis have an important place; hypospadias is not treated by surgery. In 1905, Froehlich published Pediatric Surgery Studies dealing exclusively with visceral surgery and demonstrating progress compared to Guersant's study. In 1906, Kirmisson published Pediatric Surgical Textbook, containing the first discussion of radiology and the description of the pathology of the omphalomesenteric duct and of other congenital malformations. Osteomyelitis was given its proper name, and cervical fistulas were explained. In 1914, A. Broca achieved further progress describing treatments of megacolon, intussusception, and the operation of Fredet Ramstedt. The book by Ombredanne, already out of date at the time of its publication, showed that he was not aware of the wartime, progress achieved by Ladd and Gross in the USA. French publications have diminished since then, and French pediatric surgery is still trying to find a precise identity. PMID- 3095889 TI - [Classification and characterization of oncogene products based on their homology]. PMID- 3095890 TI - [Effect of a mast cell membrane-stabilizing drug (disodium cromoglycate--Nalcrom) on hydrochloric acid secretion and the healing process in duodenal ulcer]. PMID- 3095891 TI - Quality assurance control in the EORTC cooperative group of radiotherapy. 1. Assessment of radiotherapy staff and equipment. European Organization for Research and Treatment of Cancer. AB - A quality control study was carried out by the EORTC Cooperative Group of Radiotherapy. From January 1982 to December 1984, 17 institutions were visited by a group of "experts" in radiotherapy and radiation physics. The evaluation included three steps: a comparison of megavoltage units, technical and staff environment, and data present in clinical and radiotherapy charts for each center; radiation physics calibration of photon and electron beams; and radiation physics measurements on a stimulated clinical case using an Alderson Rando anatomical phantom. This paper presents the results of Part 1. The results of Parts 2 and 3 will be analyzed in separate papers. Large variations were observed in the number of patients treated per year, per radiotherapist, per radiation physicist and per technician. On average, 400 patients were treated per year per megavoltage unit, but 8/17 centers treated more than 500 patients per unit per year. The number of simulators was suboptimal in 12/17 centers. These observations were summarized by a workload and staff index, and this index shows that in 5/17 centers major problems are present which make it difficult to comply with all the requirements of EORTC protocols. The quality of work-up regarding tumor extension was considered to be satisfactory in all centers. Dental care in patients irradiated to the head and neck was not well organized in 5/17 centers. Interaction between CT scan and dosimetry treatment planning could be improved in most centers and this should be one of the primary objectives of future quality control. PMID- 3095892 TI - Results of radiotherapy for stage II testicular seminoma. AB - Of 53 patients with Stage II seminoma treated with radiotherapy between 1970 and 1984, 9 (17%) relapsed, 5 (9%) died of testicular cancer and 1 (2%) died of intercurrent disease. Relapse rates for IIA, IIB and IIC were 11, 18 and 28% respectively. Supradiaphragmatic irradiation was not advantageous; of 22 patients receiving infradiaphragmatic irradiation, 3 (14%) relapsed, compared with 6/31 (19%) of those who had supra- and infradiaphragmatic irradiation. Despite the radioresponsiveness of seminoma, 50% of IIC patients had residual masses 4 months after radiotherapy and 20% at one year, however, this finding did not predict eventual outcome. Serum human chorionic gonadotrophin (HCG) levels were raised prior to radiotherapy in 3/26 (11.5%) Stage IIA and IIB patients and 3/10 (30%) IIC patients. However, this did not influence the outcome of radiotherapy since only 0/6 patients with raised HCG levels relapsed compared with 7/30 (23%) of those with normal levels. Analysis of the pattern of relapse together with the fact that 2/6 patients who had the extent of tumour defined at laparotomy and/or who had total abdominal irradiation relapsed, suggests that further refinement of radiotherapy is unlikely to improve the results of treatment for IIC patients and that chemotherapy should be considered the treatment of choice. PMID- 3095893 TI - Electron beam therapy in treatment of parotid neoplasm. AB - In a retrospective analysis, 42 patients with malignant primary tumor of the parotid gland were evaluated considering survival, local recurrence and tolerance of treatment. All patients referred to radiotherapy were treated by electron beam (10-15 MeV) and followed for more than 5 years. Postoperative radiotherapy after radical operation, with no macroscopic disease, was performed in 18 patients, 7 of whom were treated by radical re-operation and radiation of a recurrent parotid neoplasm. In these groups, the local recurrence rate was 4/18 (22%) and 2/7 (29%), the 5-year survival rate was 9/18 (50%) and 5/7 (71%). In 17 patients, radiotherapy started with gross tumor left behind. This group showed a local recurrence rate of 10/17 (59%) and a 5-year survival of 7/17 (41%). Treatment was well tolerated with no major sequelae. Local tumor control and its impact on survival is discussed. PMID- 3095894 TI - A comparison of build-up and depth dose characteristics of different photon beams for the treatment of Hodgkin's disease. AB - Measurements have been performed of build-up and depth-dose characteristics of photon beams under Hodgkin's disease treatment conditions as applied in two hospitals (AVL, Amsterdam and IGR, Villejuif). Although different types of accelerators, photon energies, field sizes and SSD are employed, similar dose distributions along the beam axis have been obtained in both centers. In order to explain this unexpected good agreement, the influence of the geometrical conditions of irradiation on the build-up and depth-dose distribution has been studied in detail for five photon beams (8 MV-25 MV) of three types of accelerators. PMID- 3095896 TI - Fractionated lung irradiation in young pigs with 6.2 MeV neutrons and cobalt-60. AB - Irradiations of the right lung with 6.2 MeV neutrons (38 test animals) and 60Co photons (34 test animals) were made using young pigs. Twenty animals were used as controls. Five fractions were administered in an overall treatment time of 5 or 35 days. The radiogenic pneumopathy was monitored with clinical, radiological and histological investigations, and by determining the hydroxyproline content in the lung tissue. The pneumopathy in pigs given neutrons developed after a shorter latency period and followed a more rapid and serious course than that in animals given gamma rays. While after photons the extension of the overall treatment time from 5 to 35 days led to a measurable but low increase of the ED50 this was not true for neutrons. The relative biological effectiveness (RBE) for the 6.2 MeV neutrons compared with 60Co photons was 4.0 for an overall treatment time of 5 days and 4.1 for 35 days. PMID- 3095895 TI - Biochemical monitoring of children with neuroblastoma. AB - In this article, a short review is given of the biochemical aspects of diagnosis, estimation of prognosis and follow-up of neuroblastoma in children. The importance of determination of patterns of DOPA-metabolites, rather than single metabolite assay, is stressed and illustrated by patient cases. Also the relevance of urinary cystathionine and beta-amino-isobutyric acid is indicated. PMID- 3095897 TI - Variations in immunoglobulin isotype produced during the antibody response to Brucella abortus and Staphylococcus aureus vaccines in sheep. AB - Experiments in sheep were carried out to examine factors modifying the immunoglobulin (Ig) isotype of the antibody response to Brucella abortus. Live B abortus (S19) stimulated higher titres of agglutinating antibody and IgG1 and IgG2 antibody than did killed B abortus. Live B abortus stimulated a more protracted synthesis of IgG2 antibody during the primary and secondary responses than did the killed S19 vaccine. In a second experiment, the capacity of live and killed Staphylococcus aureus to modify the antibody response to killed B abortus was examined. Both live and killed S aureus enhanced production of anti-brucella antibodies; this response was attributed to the adjuvant properties of S aureus. Killed S aureus enhanced production of anti-brucella antibody to a greater extent than live S aureus. Live S aureus did not preferentially enhance production of IgG2 anti-brucella antibody. The results suggested that the enhanced production of IgG2 antibody induced by live vaccines does not depend solely on a pyogenic lesion at the vaccination site. PMID- 3095898 TI - Haemostatic abnormalities in canine Cushing's syndrome. AB - Selected parameters of the haemostatic system were evaluated in 12 consecutive cases of canine Cushing's syndrome. The dogs did not exhibit evidence of thromboembolic complications. Levels of factors V and X were increased significantly (P less than 0.01) and fibrinogen concentration was increased modestly (P less than 0.05) in these dogs. Levels of factors IX and VIII:C remained in the reference range. Antithrombin III (ATIII) and plasminogen concentrations were markedly elevated (P less than 0.001). The low factor VIII:C and elevated ATIII levels in the plasma were not consistent with characteristics of a hypercoagulable state. These results demonstrated that haemostatic abnormalities which occur in canine Cushing's syndrome do not necessarily represent a state predisposed to thrombosis. PMID- 3095899 TI - [10 years of enteric feeding in an adult medical intensive care service]. PMID- 3095900 TI - Long-term care. PMID- 3095901 TI - Small bowel permeability in patients with nasal polyposis. AB - Small bowel absorption defects have been noted in a proportion of patients with atopic eczema. Eighteen patients with recurrent nasal polyps had the cellobiose/mannitol ratio test performed in order to assess their small bowel function. Evidence for atopy was found in 11 of 18 patients. Histologically the polyps were described as allergic but the cellobiose/mannitol ratio was normal in all cases. No evidence for a small bowel absorption defect was obtained. PMID- 3095902 TI - [Basis and reasons for dropping out of nursing studies in Tuscany]. PMID- 3095903 TI - [Professional nurses in Lombardy: survey results]. PMID- 3095904 TI - [The reform of professional education]. PMID- 3095905 TI - [Acute poisoning: a rational approach to first aid]. PMID- 3095906 TI - [Analysis of the 4 years of Rivista dell'infermiere]. PMID- 3095907 TI - [Resuscitation]. PMID- 3095908 TI - [Effects of chlorine on methylparathion and carbaryl pesticides]. PMID- 3095909 TI - Potentiation by previous nutrients of glibenclamide-induced insulin release in man. An effect which is counteracted by meal-induced retardation of drug absorption. AB - We have studied the impact of a previous meal on insulin and glucose responses to the subsequent administration of glibenclamide. Healthy volunteers and NIDDM patients ingested a standard low-carbohydrate breakfast, and glibenclamide was administered 110-120 min later either as an intravenous bolus (12.5 micrograms/kg body wt), or as a tablet (5 mg HB 419). When glibenclamide was administered i.v. the drug raised insulin and lowered blood glucose levels, and previous breakfast potentiated these effects both in healthy volunteers and in NIDDM patients. Conversely when glibenclamide was given as a tablet the drug per se raised C peptide and lowered blood glucose levels under fasting conditions, whereas the drug had no effect when ingested after breakfast. Measurements of glibenclamide in plasma revealed that previous breakfast delayed the systemic appearance of ingested glibenclamide. We conclude that nutrients sensitize insulin-releasing cells to subsequent stimulation by glibenclamide, thereby aggravate a blood glucose-lowering effect of the drug. However this effect, which could potentially induce undesirable hypoglycaemia in sulphonylurea-treated diabetics, is counteracted when glibenclamide is taken orally because of a meal-induced decrease in drug absorption. PMID- 3095910 TI - Renal function in an elderly population. A study of S-creatinine, 51Cr-EDTA clearance, endogenous creatinine clearance and maximal tubular water reabsorption. AB - There has been reported a decline in renal function with age, a decline that seems to accelerate after the age of 50. A systemically chosen sample of 70- and 75-year-old probands from the study '70-year-olds in Goteborg' have previously been examined with respect to GFR. The present study is a longitudinal follow-up of GFR in the previously examined 75-year-old probands at age 79. Renal tubular water absorption was also determined. In order to make a longitudinal comparison, S-creatinine was determined in a subsample of 166 probands, who had attended the study at 70, 75 and 79 years of age, by using frozen sera from these three examinations. S-creatinine increased slightly but statistically significant in both sexes between 70 years and 79 years of age. The reference values for EDTA clearance at age 79 calculated as M +/- 2 SD were 46-94 ml/min X 1.73 m2 BSA without any difference between the sexes. There was no change in GFR between 75 years and 79 years of age. We did not find any correlation between EDTA clearance and creatinine clearance. The tubular water reabsorption for probands without disorders was 843 +/- 92.6 (range 709-982). The results suggest that the renal filtration rate at age 79 is still good and that the ageing of the tubular function is not as pronounced as that of the GFR. PMID- 3095912 TI - Low-fat versus medium-fat enteral diets. Effects on bile salt excretion in jejunostomy patients. AB - Nine jejunostomy patients were given three low-residue enteral diets in random order through a nasogastric tube. Total bile salt excretion in the jejunostomy contents was 13-17% lower (p less than 0.05) on low-fat diets than on a medium fat diet. Cholate excretion was 14-20% lower, but chenodeoxycholate excretion showed no difference on the low-fat diets. The study supports the idea of a lower excretion of bile salts to the colon as an explanation of reduced diarrhoea when a low-fat diet is prescribed to patients after ileal resection. PMID- 3095911 TI - Effects of cimetidine on jejunostomy effluents in patients with severe short bowel syndrome. AB - The effect of the H2-receptor blocking agent cimetidine on jejunal effluent was examined in eight short-bowel patients with high-output jejunostomies. Stool mass and faecal excretion of sodium and potassium were significantly reduced by intravenous injection of 400 mg cimetidine four times a day. The amount of calcium, magnesium, phosphate, zinc, and fat in jejunostomy effluent did not change significantly. Cimetidine may be considered an antidiarrhoeal drug in extensively small-bowel-resected patients with a jejunostomy and may reduce the need for parenteral saline supply in these patients. PMID- 3095914 TI - ABO blood groups, rhesus types, and colorectal adenocarcinoma. A retrospective study of 747 cases. AB - The distribution of ABO blood groups and Rh types was studied retrospectively in 747 patients with single adenocarcinomas of the large intestine. The distributions were similar to those of healthy blood donors. Rh- patients had a more favourable stage distribution than Rh+ patients. The proportion of patients with localized disease was higher for Rh- patients than for Rh+ patients (66% versus 46%), whereas metastases into regional lymph nodes were more common among Rh+ patients (23% versus 9%). The observed relationship between Rh type and stage distribution suggests that Rh+ patients with colorectal cancer are less protected against tumour spread than Rh- patients, especially with regard to regional lymph node metastases. PMID- 3095913 TI - A double-blind crossover study of the effect of a chromone carboxylic acid, FPL 52694, on overnight fasting gastric acid secretion. AB - The chromone FPL 52694 is a preparation thought to act by stabilizing mast cell membranes, thus reducing free histamine in the gastric mucosa. The effect of FPL 52694 on overnight gastric secretion was tested in 15 dyspeptic individuals in a double-blind crossover study. Each individual received the chromone preparation or placebo for 1 week. After each of the treatment periods gastric secretion was collected after 6 h of fasting by continuous suction for 8 h during the night. A significant reduction of the total acid secretion was observed after active drug compared with placebo administration, mean reduction being 17% (median, 23%). No difference was observed between 30-min and 60-min periods. FPL 52694 had no significant effect on pepsin, intrinsic factor (IF) or volume secretion. The difference in the effect on pepsin and acid secretion, reflected in a significant increase in the pepsin to acid ratio, indicates that intrinsic histamine, similarly to extrinsic histamine, has a specific effect on parietal cells. The difference in effect on acid and IF secretion indicates that intrinsic histamine not only has a specific effect on parietal cells but also has different effects on the secretory substances contained in this cell. Since IF was not reduced by the use of FPL 52694, it may be that this substance will not influence vitamin B12 metabolism. PMID- 3095915 TI - Serum amyloid protein A (SAA): an indicator of inflammation in AIDS and AIDS related complex (ARC). AB - The acute phase protein serum amyloid A (SAA) and C-reactive protein (CRP) were measured in a group of 30 homo- and bisexual males with AIDS, 31 males with AIDS related complex (ARC) and 23 healthy male homosexual controls (HC) in Copenhagen. The mean values of SAA and CRP were significantly higher in the AIDS group compared to the two other groups. SAA was elevated also in the ARC group, whereas the mean CRP value was normal. No increase in SAA and CRP was found in the HC group. The AIDS patients with Pneumocystis carinii infections had the highest SAA values, those with Kaposi's sarcoma the lowest. The elevations in SAA and CRP preceded episodes of acute opportunistic infections often by several days before the infectious agents were identified. We conclude that patients with AIDS are able to establish an acute phase response as reflected by elevated SAA and CRP, and that measurement of these proteins may be of diagnostic and prognostic value. PMID- 3095916 TI - Effects of norfloxacin on the faecal flora in patients with complicated urinary tract infections. AB - The effects on the long-term use of norfloxacin, a fluorinated 4-quinolone, on the intestinal flora (both aerobic and anaerobic), were evaluated in patients suffering from recurrent complicated urinary tract infections. Eight patients received norfloxacin 400 mg b.i.d. for three months, and 11 patients received 400 mg b.i.d. for one month, and then 400 mg as an evening dose for two months. The concentration of Enterobacteriaceae, staphylococci, Streptococcus faecalis, and yeasts in stool specimens, together with the norfloxacin concentration were measured every month. The beta-aspartyl-glycine test was carried out at the same time. No urinary tract infections, either of exogenous (Pseudomonas spp.) or endogenous origin could be diagnosed during norfloxacin therapy. At both dosages of norfloxacin the faecal samples were free of Enterobacteriaceae due to low minimal bactericidal concentrations and high faecal drug concentrations. The suppressive effect was selective in that the anaerobic flora was left intact. A suppression of the aerobic intestinal flora could lead to an important reduction of recurrent infections of the urinary tract in these patients. PMID- 3095917 TI - Norfloxacin in the therapy of gonococcal infections. AB - Norfloxacin is a quinolone derivative with demonstrated activity against Neisseria gonorrhoeae. The MIC90 against penicillinase- and non-penicillinase producing N. gonorrhoeae is 0.06 mg/l and 0.015 mg/l respectively. The drug is rapidly absorbed with a single oral dose of 800 mg producing peak serum levels of 2.45 mg/l. In this open, uncontrolled study, 70 patients with laboratory confirmed, uncomplicated infections with N. gonorrhoeae were entered to determine the efficacy and safety of a single oral dose of norfloxacin 800 mg. Thirty-one males and 27 females were evaluated for efficacy with 34 males and 25 females evaluated for safety. Norfloxacin cured all 31 urethral and two pharyngeal infections in men. All 25 females with endocervical infections and six with rectal involvement were also cured. The single treatment failure occurred in a woman who had persistent pharyngeal infection. All isolates of N. gonorrhoeae were inhibited by 0.05 mg/l of norfloxacin. The incidence of adverse effects was 23.7% but all were mild, required no specific therapy and cleared without sequelae. In this study, norfloxacin proved to be an effective agent in the therapy of uncomplicated gonococcal infection in males and females. It has previously been proven to be useful in the therapy of gonococcal infections due to penicillinase-producing N. gonorrhoeae and the value of this drug as a first line choice in the treatment of gonococcal infections is discussed. PMID- 3095918 TI - [Polyneuropathy, organomegaly, endocrinopathy and skin changes in a case of solitary myeloma]. AB - The case is reported of a 32-year-old woman with polyneuropathy, organomegaly, edema, endocrinopathy, dark skin and solitary myeloma with monoclonal gammopathy of IgG/lambda type. More than 100 cases of this rare disorder have been observed up to now, mainly in Japan. In recent reviews the terms POEMS-syndrome or Crow Fukase-syndrome have been used. Local radiotherapy of the myeloma led to lasting regression of symptoms. Studies with immunocytochemistry and immunoelectroblotting revealed specific antibody activity against hypophysis, suggesting that the pathologic monoclonal myeloma antibodies may damage the neuroendocrinic centers in hypothalamus and hypophysis as the primary target. Most of the multisystemic symptoms would thus be explained as secondary alterations. PMID- 3095919 TI - [The value of the guaiac test in the screening of colorectal tumors]. AB - The sensitivity, specificity and positive predictive value of fecal blood testing are too poor to allow its general use as a screening test for colorectal cancers. Even the predictable qualitative improvement of these tests will be of no avail with regard to non-tumoral sources of bleeding or the non-hemorrhagic tumoral sources of bleeding or the non-hemorrhagic tumours which are frequent in the early stages of colorectal cancer. It is therefore essential to define high-risk groups, to pay particular attention even to minor symptoms, and to perform the necessary endoscopic or radiological diagnostic tests. PMID- 3095920 TI - Use of nitroglycerin--1986. PMID- 3095921 TI - Pertussis toxin inhibition of B cell and macrophage responses to bacterial lipopolysaccharide. AB - Lipopolysaccharide, a component of the outer membrane of Gram-negative bacteria, activates B lymphocytes and macrophages. Pertussis toxin, which inactivates several members of the G protein family of signaling components, including Gi and transducin, was found to inhibit the lipopolysaccharide-induced responses of the WEHI-231 B lymphoma cell line and the P388D1 macrophage cell line. These results, combined with the demonstration that lipopolysaccharide inhibits adenylate cyclase activity in P388D1 cells, strongly argues that lipopolysaccharide activation of cells is mediated by a Gi-like receptor-effector coupling protein. PMID- 3095922 TI - Novel interleukin-2 receptor subunit detected by cross-linking under high affinity conditions. AB - Interleukin-2 (IL-2) binds to both high- and low-affinity classes of IL-2 receptors on activated T lymphocytes. Only the high-affinity receptors are involved in receptor-mediated endocytosis and normally transduce the mitogenic signals of IL-2; however, the structural features distinguishing the high- and low-affinity receptors are unknown. When 125I-labeled IL-2 was chemically cross linked to activated human T lymphocytes, two major bands were identified. First, as predicted, a 68- to 72-kilodalton band, consisting of IL-2 (15.5 kilodaltons) cross-linked to the IL-2 receptor (55 kilodaltons), was observed. Second, an unpredicted 85- to 92-kilodalton moiety was detected. This band was not present when IL-2 was cross-linked to transfected C127 cells, which exclusively express low-affinity receptors. The data presented are most consistent with the existence of a 70- to 77-kilodalton glycoprotein subunit (p70) which, upon associating with the 55-kilodalton low-affinity receptor (p55), transforms it into a high-affinity site. It is proposed that p55 and p70 be referred to as the alpha and beta subunits, respectively, of the high-affinity IL-2 receptor. PMID- 3095923 TI - Induction of altered c-src product during neural differentiation of embryonal carcinoma cells. AB - The expression of the cellular src gene product pp60c-src was examined in an embryonal carcinoma cell line that differentiates in vitro into neuronlike cells after being treated with retinoic acid. Quantitative and qualitative changes in c src expression accompanied the events associated with neuronal differentiation. The levels of pp60c-src increased 8- to 20-fold during the period when the cells elaborated neuritic processes and expressed neuron-specific proteins. The electrophoretic mobility of pp60c-src induced in these cells was retarded in comparison with that in untreated cells or in treated cells before neurite elaboration. The shift in electrophoretic mobility was due to an alteration in the amino terminal 16,000 daltons of pp60c-src and similar to an alteration of c src protein found in neural tissues and in pure primary cultures of neuronal cells. These results indicate that expression of pp60c-src induced by retinoic acid in these embryonal carcinoma cells mimics the expression of c-src in developing neurons. Therefore, this embryonal carcinoma cell line provides a model system to investigate the function of the src protein in neuronal differentiation. PMID- 3095924 TI - CNS and hypoderm regulatory elements of the Drosophila melanogaster dopa decarboxylase gene. AB - Expression of the dopa decarboxylase gene (Ddc) is regulated in a tissue- and developmental stage-specific manner throughout the life cycle of the fruit fly, Drosophila melanogaster. Essential Ddc regulatory elements lie within 208 base pairs upstream from the RNA start point. Functional elements within this 5' flanking region were mapped by deletion analysis, which assayed expression in vivo after germline integration via P element vectors. One of the elements is essential for expression in both the larval and adult central nervous system, and at least two other elements are necessary for quantitatively normal expression in the hypoderm. Within each of the intervals that have regulatory effects are found sequence elements conserved between the Ddc genes of two distantly related species of flies. On the basis of this correlation, regulatory functions for these sequence elements can be postulated. PMID- 3095925 TI - Alterations in T4 (CD4) protein and mRNA synthesis in cells infected with HIV. AB - Cells infected with the human immunodeficiency virus (HIV) show decreased expression of the 58-kilodalton T4 (CD4) antigen on their surface. In this study, the effect of HIV infection on the synthesis of T4 messenger RNA (mRNA) and protein products was evaluated in T-cell lines. Metabolically labeled lysates from the T4+ cell line Sup-T1 were immunoprecipitated with monoclonal antibodies to T4. Compared with uninfected cells, HIV-infected Sup-T1 cells showed decreased amounts of T4 that coprecipitated with both the 120-kilodalton viral envelope and the 150-kilodalton envelope precursor molecules. In four of five HIV-producing T cell lines studied, the steady-state levels of T4 mRNA were also reduced. Thus, the decreased T4 antigen on HIV-infected cells is due to at least three factors: reduced steady-state levels of T4-specific mRNA, reduced amounts of immunoprecipitable T4 antigen, and the complexing of available T4 antigen with viral envelope gene products. The data suggested that the T4 protein produced after infection may be complexed with viral envelope gene products within infected cells. Retroviral envelope-receptor complexes may thus participate in a general mechanism by which receptors for retroviruses are down-modulated and alterations in cellular function develop after infection. PMID- 3095926 TI - Acetylation of antithrombin III by aspirin. AB - Although the effect of aspirin in blood coagulation has been believed to be due to its ability to interfere with platelet function, very few studies have reported its effect on various blood coagulation proteins. Since aspirin (acetylsalicylic acid) is known to acetylate numerous biologic macromolecules, the effect of aspirin on antithrombin III was investigated. It was found that antithrombin III is irreversibly inactivated by treatment with aspirin. The inactivation follows pseudo first-order kinetics and incorporation of one molecule of aspirin per molecule of the protein is necessary for complete inactivation. Reaction with acetyl-[14C]-salicylic acid incorporated 1.4 mol of acetyl group per mole of protein but reaction with carboxyl-[14C]-acetyl salicylic acid incorporated only 0.03 mol of radioactive label per mole of the protein. Furthermore, sodium salicylate does not inactivate the protein. This suggests that the reaction occurs through the acetylation of antithrombin III. Amino group analysis of aspirin-treated antithrombin III using trinitrobenzenesulfonic acid revealed that one to two primary amino groups are lost relative to the untreated antithrombin III. It is concluded that the reaction of aspirin with antithrombin III results in specific acetylation of lysine residues. PMID- 3095927 TI - Rapid release and deactivation of plasminogen activators in human endothelial cell cultures in the presence of thrombin and ionophore A23187. AB - alpha-Thrombin, DFP-thrombin, and ionophore A23187 induce the rapid release (less than 5 minutes) of a variety of proteins, including t-PA forms (Mr 110 and 70 k, after SDS-PAGE) from primary cultures, and both t-PA and u-PA (Mr 90 and 54 k) from subcultured human HUVECs. All PA activity forms are rapidly decreased in the releasates by some unknown mechanism. gamma-Thrombin does not induce the release of PAs from cultured HUVECs. PMID- 3095928 TI - Recent advances in the immunologic classification of leukemia. AB - Important insights into leukocyte differentiation and the cellular origins of leukemia have been gained through the use of monoclonal antibodies that define cell surface antigens and molecular probes that identify immunoglobulin and T cell receptor genes. Results of these studies have been combined with markers such as surface membrane and cytoplasmic immunoglobulin on B lymphocytes, sheep erythrocyte receptors on T lymphocytes, and cytochemical stains. Using all of the above markers, it is now clear that acute lymphoblastic leukemia (ALL) is heterogeneous. Although monoclonal antibodies are useful in distinguishing acute myeloid from acute lymphoid leukemias, they have less certain usefulness in the subclassification of acute myelogenous leukemia (AML). Attempts to subclassify AML by differentiation-associated antigens rather than by the French-American British (FAB) classification are underway in order to document the potential prognostic usefulness of surface markers. PMID- 3095929 TI - An alternate level of care, the prospective payment system and the challenge of extended care. AB - Due to demographic, morbidity and public policy shifts, the health care system is undergoing a profound change. In this unsettled context the problem of the alternate level of care (ALC), or sub-acute care, patient has acquired a new meaning and importance. An ALC patient falls between the traditional levels of acute and skilled care. This study tries to identify the nature and scope of the ALC problem in Illinois, because it is symptomatic of changing morbidity patterns; because it exemplifies the consequent dilemmas for the health care industry; and because it typifies the ambivalent response of the health care institutions. The data reveals that the ALC patients are backed up in 78% of the hospitals in the state, and they pose a heavy burden and future risk both to hospitals and nursing homes. The hospital industry has sensed the challenge of extended care, but it is not responding with a reasoned and concerted strategy. Rather, in a worsening competitive situation, a unique opportunity to bridge the hiatus between acute and long-term care, and to build towards a humane and equitable system of care, may pass us by. PMID- 3095930 TI - Needle-catheter jejunostomy for postoperative nutritional support. AB - Use of the needle-catheter feeding jejunostomy at Richland Memorial Hospital and the Dorn Veterans Administration Hospital, both clinical teaching institutions of the University of South Carolina School of Medicine, has been evaluated in 114 patients ranging from 20 to 90 years old. The results of this survey span a 36 month period, from Jan 1, 1982 to Jan 1, 1985, in which jejunostomy catheters were inserted via a subserosal approach to provide early postoperative enteral support after elective and emergency surgical procedures. Of the 114 patients who had the catheter inserted, 82 (72%) completed a course of enteral tube feedings without complications, whereas 32 (28%) had either mechanical or metabolic complications leading to temporary or permanent cessation of feeding. One patient had a serious midjejunal volvulus, resulting in extensive jejunal necrosis and subsequent resection, a heretofore unpublished complication of this technique. The median number of days with catheter per patient was 18, with a range of one to 98 days. Only four (3.5%) of the catheters inserted were not used. Nutritional parameters were maintained or improved in all patients reviewed. The results of this study encourage the insertion of a feeding jejunostomy catheter as a complementary surgical procedure in patients expected to have a catabolic postoperative course, and who are therefore in need of aggressive nutritional support. PMID- 3095931 TI - [Patterns of hospital morbidity]. PMID- 3095932 TI - [Social and economic repercussions of helminthiases transmitted by the soil]. PMID- 3095933 TI - Viral hepatitis in southern Africa. PMID- 3095934 TI - Rickettsial vaccines with emphasis on epidemic typhus. Initial report of an old vaccine trial. PMID- 3095935 TI - Some aspects of bilharzia in southern Africa. PMID- 3095936 TI - Manson's schistosomiasis--progress and continuing problems. PMID- 3095937 TI - Endocrine responses after thyrotrophin-releasing hormone stimulation and dexamethasone suppression tests in the major depressive syndrome. AB - The effects of dexamethasone 1 mg on plasma cortisol levels and of thyrotrophin releasing hormone (TRH) 200 micrograms on thyrotrophin (TSH), growth hormone and prolactin levels in 107 patients with a major depressive disorder (MDD) were compared with those in 87 healthy subjects. Individual hormonal responses and combinations of hormonal responses after administration of dexamethasone and TRH were evaluated as diagnostic aids for MDD by calculating sensitivity, specificity and efficiency for single and multiple hormonal abnormalities. In patients suffering from MDD, 65% of men, 74% of reproductive women and 71% of menopausal or hysterectomized (H/M) women had abnormal responses (sensitivity) to a dexamethasone suppression test (DST). When the DST and TSH responses to TRH were combined, 85% of men, 87% of reproductive women and 84% of H/M women had abnormal results. If the efficiency of the different combinations of hormone responses is calculated, a totally different picture emerges. PMID- 3095939 TI - Clinical significance and etiology of infected catheters used for total parenteral nutrition. AB - Catheter related sepsis (CRS) is the most serious complication of total parenteral nutrition. Frequently, however, low rates of CRS are associated with a high incidence of infection of the catheter tip, the clinical significance of which is unclear. The relationships between CRS, infection of the catheter tip and infection at the site of catheter insertion have been investigated in 283 catheters of 257 patients receiving total parenteral nutrition. CRS occurred in only ten patients (3.5 per cent) whereas organisms were isolated from 108 catheter tips (38.2 per cent). The most common organism isolated was Staphylococcus epidermidis (66.7 per cent). Eight catheter tips were colonized from a distant septic focus. Organisms were isolated from 90 catheter tips which were removed electively from patients who displayed no clinical evidence of sepsis. There was a poor correlation between infected catheter tips and infected catheter insertion sites. Asymptomatic infection of the catheter tip appears to be of little clinical relevance, resulting in no patient morbidity. Contamination of the catheter tip during or after removal seems to account for a significant proportion of these infections. PMID- 3095938 TI - An expanded social work role in a university hospital-based group practice: service provider, physician educator and organizational consultant. AB - This paper reports the development of social work role and functions in a primary medical group practice which was established to replace the general medical clinics of a large urban voluntary teaching hospital in an academic medical center. It traces the shaping and implementation of a role which is functionally integral to the care, teaching and research goals of the practice; is operationalized into its service delivery system; and utilizes a full range of sophisticated social work skills. Along with physicians and nurse practitioners, the social worker is a principal provider of patient care, as well as physician educator and organizational consultant who contributes to coordinated, comprehensive and resource conservative care. Implications for other settings are noted. PMID- 3095940 TI - [Chest wall moulages for radiotherapy of resected breast cancer with fast electrons: comparative tests of different materials]. AB - Irradiation of the thoracic wall with high-speed electrons is one of the standard methods of prophylaxis and therapy of local recurrences and cutaneous metastases of an operated mammary carcinoma. The surface dose, however, is only 85% of the maximum dose, due to the depth dose curve of the electron beams with the preponderantly applied energy of 7MeV. This is a poor value, since most of all recurrences appear near to the surface and so the risk of giving an insufficient dose is involved. The dose distribution could be essentially improved by the use of moulages on the chest. These moulages were made of different materials which were tested and compared with respect to their suitability for radiotherapeutic purposes. The best materials proved to be "Urgo-Plastan" (manufacturer: Holphar, Sulzbach) and "Orthoplast" (manufacturer: Johnson & Johnson, Dusseldorf). Both materials are synthetic substances which after heating can easily be adapted to the body shape and which offer a good stability, little inconvenience for the patient and a relative easy handling. With these moulage materials, the surface dose is increased to 98% ("Urgo-Plastan") and 99% ("Orthoplast") of the maximum dose. PMID- 3095941 TI - [Report on the planned supply of radiotherapy equipment in Baden-Wurttemberg]. PMID- 3095942 TI - Action of carnosine and beta-alanine on wound healing. AB - In rats treat-given hydrocortisone to suppress healing, tensile strength of the skin at the site of an incision wound was significantly higher in rats locally treated with carnosine than in untreated animals. Similar effects on the tensile strength of the skin were observed by the administration of beta-alanine and histidine, but not of beta-alanine alone. Exogenous carnosine was degraded in the body by carnosinase and histidine decarboxylase to yield histamine. Since beta alanine, the other degradation product of carnosine, was found to stimulate the biosynthesis of nucleic acids and collagen, histamine derived from carnosine is considered to have enhanced the process of wound healing by stimulating effusion at the initial stage of inflammation. Thus, the enhancement by carnosine of wound healing may be ascribed to stimulation of early effusion by histamine and of collagen biosynthesis by beta-alanine. The wound-healing effects of carnosine were further demonstrated by the observation that carnosine significantly increased granulation suppressed by cortisone, mitomycin C, 5-fluorouracil, and bleomycin. PMID- 3095943 TI - The costs and dynamics of surgical morbidity and mortality. AB - The implementation of prospective payment systems for hospitals, most notably the Medicare diagnosis-related group (DRG) mechanism, will encourage surgeons and hospitals to characterize populations that create financial risk. Our previous studies have demonstrated that certain factors (identifiers) such as emergency admission or necessity for blood transfusion would predict higher cost patients per DRG and that some populations (i.e., surgical intensive care unit admissions) would generate significant financial risk under DRG reimbursement. The purpose of this project was to test the assumption that surgical complications and deaths would generate financial risk under DRGs and that the degree of risk would vary by the dynamics of the complications and death. We examined all surgical admissions (n = 5596) to a large voluntary teaching hospital to determine all general and vascular surgical complications and deaths (170 admissions; complication rate 3.1%) for 1983 and 1984. Total charges (exclusive of physicians' fees) of these patients were $4,683,670 (mean per patient, $27,551) versus DRG revenues of $2,378,703 (mean per patient, $13,992) resulting in a loss of $2,304,967 (mean per patient, $13,558). Charges and financial risk generated by the origin of the surgical morbidity and death differed as follows: iatrogenic origin only (N = 41)--mean charge per patient, $15,321 (19.5% of whom had unusually long hospital stays or unusually high costs [outliers]; origin intrinsic to the patient's disease only (N = 75)--mean charge per patient, $28,391 (38.7% outliers); and combined iatrogenic origin and patient's disease (N = 54)--mean charge per patient, $35,669 (48.0% outliers) (group 1 versus groups 2 and/or 3; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095944 TI - Pharmacokinetics and effects on fibrinolytic and coagulation parameters of two doses of recombinant tissue-type plasminogen activator in healthy volunteers. AB - Pharmacokinetics and pharmacological effects of two intravenous doses of recombinant tissue-type plasminogen activator (rt-PA) (40 and 60 mg over 90 min) were determined in healthy volunteers. Mean maximum plasma concentrations were 1080 and 1560 ng/ml respectively. The steady state level during subsequent maintenance infusion of 30 mg over 6 h was 250 ng/ml. The pharmacokinetics of rt PA showed a bi-exponential disappearance from plasma consistent with a 2 compartment model of t1/2 alpha = 5.7 min, a t1/2 beta = 1.3 h and a total clearance of 380 ml/min. Mean fibrinogen levels at the end of the infusions of 40 mg or 60 mg rt-PA over 90 min, measured in thawed plasma samples collected on citrate/aprotinin, decreased to 74% and 57% of the preinfusion values respectively. Plasminogen fell to 55% and 48%, and alpha 2-antiplasmin to 28% and 18% of initial values. No further decrease of these parameters was observed during the infusion of 30 mg rt-PA over 6 h. Only 2% of the preinfusion fibrinogen levels could be recovered as fibrinogen-fibrin degradation products. This moderate extent of systemic fibrinogenolysis is much less than that reported for therapeutic i.v. infusions of streptokinase. PMID- 3095945 TI - Association between postoperative hyper-response in t-PA inhibition and deep vein thrombosis. PMID- 3095946 TI - Absence of synergism between tissue-type plasminogen activator (t-PA), single chain urokinase-type plasminogen activator (scu-PA) and urokinase on clot lysis in a plasma milieu in vitro. AB - A potential synergic effect of tissue-type plasminogen activator (t-PA), single chain urokinase-type plasminogen activator (scu-PA) or urokinase on clot lysis was investigated in a whole human plasma system in vitro. The system consisted of a human plasma clot labeled with 125I-fibrinogen, immersed in citrated whole human plasma, to which the thrombolytic agents were added. Clot lysis was quantitated by measurement of released 125I, and activation of the fibrinolytic system in the surrounding plasma by measurements of fibrinogen and alpha 2 antiplasmin. t-PA, scu-PA and urokinase induced a dose-dependent and time dependent clot lysis; 50 percent lysis after 2 h was obtained with 5 nM t-PA, 20 nM scu-PA and 12 nM urokinase. At these concentrations no significant activation of the fibrinolytic system in the plasma was observed with t-PA and scu-PA, whereas urokinase caused significant alpha 2-antiplasmin consumption and concomitant fibrinogen degradation. The shape of the dose-response curves was different; t-PA and urokinase showed a log linear dose-response whereas that of scu-PA was sigmoidal. Combinations of t-PA and scu-PA, of t-PA and urokinase or of scu-PA and urokinase at thrombolytic doses of each showed no synergism for thrombolysis. Fifty percent clot lysis in 2 h was obtained at total concentrations of the combined agents of 5 to 15 nM with molar ratios ranging from 1:4 to 4:1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3095947 TI - Correlation of antibodies to LAV/HTLV III in hemophiliacs with the use of virus inactivated clotting factors. AB - The retrovirus LAV/HTLV III, highly likely to be responsible for the acquired immunodeficiency syndrome (AIDS) in some recipients of blood products, can be inactivated by chemical and/or heat treatment, so the use of virus-inactivated factor VIII and factor IX preparations for treating hemophilia A and B has become important. We examined hemophilic children and found that those children treated since 1979 with virus-inactivated preparations did not develop antibodies against LAV/HTLV III. In contrast, 77% of patients treated with conventional factor VIII or factor IX preparations had antibodies against this virus. PMID- 3095949 TI - [Laboratory criteria for malnutrition]. PMID- 3095948 TI - Role of heparin in tumor cell-induced platelet aggregation. AB - B16 mouse melanoma cell lines (B16F1, B16F10 and B16BL6) were able to induce platelet aggregation, and concomitant release of ATP in heparinized platelet-rich plasma (PRP). In citrated PRP, these tumor cells did not induce platelet aggregation. Addition of heparin to citrated PRP enabled these tumor cells to induce aggregation. In heparinized PRP, platelet aggregates induced by B16F10 cells were dissociated by the addition of either 4 mM EDTA, 10 mM CaCl2 or 0.1 micrograms/ml protamine sulfate. B16F10-induced aggregation in heparinized PRP was inhibited by preincubation with anti-fibronectin antibody, but not with antifibrinogen or anti-von Willebrand factor antibodies. B16F10 cells induced aggregation in washed platelet suspension with the addition of heparinized platelet-poor plasma (PPP). Cryoprecipitate from human plasma showed the same effect in the presence of heparin if substituted for PPP. The mixture of purified fibronectin, von Willebrand factor, fibrinogen and heparin were less effective than cryoprecipitate on B16F10-induced aggregation of washed platelets. The results suggest that an interaction between fibronectin and heparin may be important in tumor cell-induced aggregation. PMID- 3095950 TI - [Parenteral nutrition in one big bag. Routine use of standardized mixtures in hospitals]. PMID- 3095951 TI - [Ossification of muscle-tendon insertions on the ischiadic tubercle and pubic bone in a truck-driver]. PMID- 3095952 TI - Spontaneous and MMC induced SCE in lymphocytes from patients with cervical cancer. AB - The frequencies of spontaneous and mitomycin C (MMC) induced sister chromatid exchanges (SCEs) were investigated in lymphocytes of the peripheral blood of women in different stages (O-III) of cervical cancer. Average generation time (AGT) was also examined by the replicative index (R.I.) method. The following results were obtained: The spontaneous SCE frequency was found to be significantly higher in the cancer group than in the control group; 8.21 +/- 1.42 (mean +/- S.D.) against 5.62 +/- 0.55. The SCE frequency gradually increased with the progression of the cervical cancer. The SCE frequency in patients with carcinoma in situ (CIS), the lowest stage of cervical cancer, was significantly higher than that of the controls. The frequency of MMC induced SCE was higher than that of spontaneous SCE in all groups, and the difference in frequency between MMC induced and spontaneous SCEs of cervical cancer group of the stages I III was significant by different from that of the control group. The AGT of the cervical cancer group was shorter than that of the control group, but it was not statistically significant. PMID- 3095953 TI - Intermediate term results of isolated mitral valve replacement with glutaraldehyde-preserved porcine xenograft valve: clinical and hemodynamic comparison between Hancock valve and Angell-Shiley valve. AB - Clinical and hemodynamic assessments were carried out for 30 cases, who underwent isolated mitral valve replacement with glutaraldehyde-preserved porcine xenograft valve. The cases were divided into two groups, according to the types of prostheses. Group H comprised 23 cases with Hancock 342 valve and group AS, 7 cases with Angell-Shiley valve. Mean (S.D.) follow-up periods were 4.0 +/- 0.7 in group H and 4.6 +/- 0.6 years in group AS. Incidence of valvular malfunction was 3.3 in group H and 9.3% per patient-year in group AS. Cumulative survival and event-free rates were calculated by actuarial method, which revealed 91 and 83% in group H and 70 and 71% in group AS at 6 years after operation. Hemodynamic assessments were carried out in 20 cases, in which complete data at rest and during exercise were obtained. Valvular function deteriorated during exercise in both groups. Parameters showing valvular function in group AS were worse than those in group H. It is concluded from this study that intermediate late results are satisfactory in group H, incidence of valvular malfunction is high in children and in group AS, thromboembolisms are seen even in cases with recourse to anticoagulant, xenograft valves are stenotic especially in high flow state and valvular function of AS valve is inferior to H valve. PMID- 3095954 TI - Electron microscopic study of the cell surface of dibekacin-treated Pseudomonas aeruginosa. AB - Electron microscopy of thin sections of Pseudomonas aeruginosa IAM 1007 treated with dibekacin revealed blebs, disintegration of the outer membrane of the cell wall and degenerative features of the cytoplasm. In the next experiment, the cell wall fraction was isolated from the mechanically disrupted cells, incubated with dibekacin and was subjected to electron microscopy, in order to find a clue to the action mechanism of dibekacin on the cell wall of Pseudomonas aeruginosa IAM 1007. As a result, it was found that unidentified substances were released from the surface of the cell wall and that the outer membrane of the cell wall disappeared. The degree of changes of the cell wall ultrastructure was almost proportional to the length of incubation with dibekacin. These findings strongly suggest that dibekacin directly disintegrates the outer membrane of the cell wall of Pseudomonas aeruginosa IAM 1007. PMID- 3095955 TI - Cross-reactivity and neutralization by rabbit antisera raised against crotoxin, its subunits and two related toxins. AB - Antisera were raised against intact crotoxin (Crotalus durissus terrificus), Mojave toxin (Crotalus scutulatus scutulatus) and concolor toxin (Crotalus viridis concolor), as well as the subunits of crotoxin. Double immunodiffusion and enzyme-linked immunosorbent assays (ELISA) demonstrated antigenic similarity between these three purified toxins and their subunits. Additionally, when crotoxin antisera were pre-incubated with each of the three toxins before injection, the lethal activity of all were neutralized equally well. Antiserum was considerably more effective in neutralizing crotoxin in vivo when the toxin was injected i.m. than when injected i.v. Antisera against both intact crotoxin and its basic subunit were an order of magnitude more effective than crotoxin acidic subunit antiserum in crotoxin neutralization. Purified phospholipase A2 from Crotalus adamanteus and Crotalus atrox showed weak cross-reactivity with antisera raised against intact crotoxin and its subunits in the ELISA. Our results suggest that crotalid neurotoxins can be detected and neutralized by polyclonal antibodies raised against any intact toxin or basic subunit in this group of homologous toxins. PMID- 3095956 TI - Benoxaprofen photosensitization of phospholipase activation in mammalian cells in culture. AB - Benoxaprofen (BPF) induces a clinical photosensitivity which resembles idiopathic solar urticaria. This response is mediated by degranulation of mast cells. Since mast-cell degranulation is known to be modulated by phospholipid alteration, we examined the effect of BPF and ultraviolet radiation (UV) on phospholipid metabolism of C3H 10 T1/2 cells in culture. BPF + UVB (280-320 nm) induced release of [3H]arachidonic acid (AA) but did not alter the release of [3H]choline from prelabelled cells. This suggests that BPF photosensitizes phospholipase A2 activation. Such activation probably represents an integral step in the mechanism of BPF photosensitization of mast-cell degranulation. PMID- 3095957 TI - Decreased pulmonary drug metabolism in mice treated with the PCB metabolite 4 methylsulphonyl-2,2',5,5'-tetrachlorobiphenyl. AB - 4-Methylsulphonyl-2,2',5,5'-tetrachlorobiphenyl (4-MeSO2-TCB) is a major polychlorinated biphenyl (PCB) metabolite present in lung tissue of PCB-exposed human subjects. After treatment of mice with 4-MeSO2-TCB (100 mg/kg), the pulmonary N-demethylation of aminopyrine in vitro was significantly decreased, while hepatic N-demethylation was concomitantly increased, as compared to tissue from control mice. Treatment of mice with 4-MeSO2-TCB also decreased the in vivo pulmonary covalent binding of o,p'-DDD, while the in vivo hepatic covalent binding was increased. The results indicate that 4-MeSO2-TCB inhibits or represses a cytochrome P-450-dependent enzyme activity in the mouse lung, while in contrast this activity is induced in the mouse liver. PMID- 3095958 TI - The use of biological monitoring in the estimation of exposure during the application of pesticides. AB - In order to assess the occupational health risk to workers using pesticides, accurate data on exposure (including knowledge of the primary route of exposure) and on absorption are needed. In addition, a well-defined no-effect level (NOEL) derived from suitable animal data must be available. Biological monitoring, urinary metabolite excretion in particular, frequently is used to indicate whether a worker has been exposed. Interpretation of the toxicological significance of the observed urinary metabolite levels is often difficult because the relationship between these levels and toxic dose are generally unknown. Another complication is the apparent lack of correlation between patch data and urinary metabolite data. The usefulness of a metabolite to predict exposure depends on many things, including detailed knowledge of absorption and excretion characteristics of the parent compound and identification of the metabolites. These data, when combined with appropriate toxicology data, permit an analysis of the potential health risks associated with an occupational exposure to toxic chemicals. This paper will correlate data from a number of studies in which the dermal penetration of azinphosmethyl (AM) was measured in rats, rabbits, monkeys and man; and urinary alkyl phosphate metabolites were measured in orchardists exposed to AM. The feasibility of utilizing metabolite excretion to estimate exposure and ultimate risk will be discussed. PMID- 3095960 TI - Blood group incidence and Escherichia coli bacterial sepsis. AB - Many strains of Escherichia coli possess an antigen that reacts with naturally occurring antibodies to human red cell B antigens. The authors tested the hypothesis that the presence of naturally occurring anti-B isoagglutinins afford protection against the development of E. coli septicemia. The blood groups found in 115 patients with E. coli septicemia were compared with those found in three "control" populations: 138 patients with septicemia due to other organisms, 23,135 hospitalized patients, and 40,038 normal blood donors. The relative incidence of B and AB blood groups (not containing anti-B antibodies) was significantly higher than A and O blood groups (containing anti-B antibodies) in the group with E. coli septicemia. This finding supports the hypothesis. PMID- 3095959 TI - Anti-Rh33, the second separable example, also made by a person who made anti-D and has C+ red cells. AB - A complex serologic investigation resulted in identification of the second example of separable anti-Rh33. A patient who had been transfused frequently and who had red cells that lacked a portion or portions of the D mosaic of antigens made anti-D against that portion of D missing from her red cells, anti-c, anti-V, anti-Rh33, anti-K, and an autoantibody that mimicked the reactions of anti-D. Differential adsorption experiments showed that the anti-Rh33 was separable from the other antibodies present. The serologic findings in this case and in the study in which anti-Rh33 was first found show some sort of relationship between D and Rh33. First, one of the genes, RoHar, that makes Rh33 makes a form of D that is difficult to detect. Second, the only other gene thus far known to make Rh33, DIV (C)-, encodes for a form of D from which portions of the D mosaic are missing. Third, both examples of separable anti-Rh33 were made by women who made anti-D and whose red cells were C+. PMID- 3095961 TI - Separation from mother at time of weaning. A rarely discussed aspect of the aetiology of protein energy malnutrition. PMID- 3095962 TI - [Induction of the switch in the synthesis of immunoglobulin classes in the RPM 1 6410t lymphoblast cell line and its clones as affected by fetal calf serum factors]. AB - We have found that human lymphoblastoid cell line RPMI-6410t is a biochemical mutant for gene of thymidine kinase and has chromosome markers in the karyotype. Thus, this cell line can be used as a partner in somatic hybridization, in particular for producing hybridomas, synthesizing human monoclonal antibodies. We have discovered that line RPMI-6410t carries HLA-A2, -B7 and -B12 antigens of human histocompatibility complex on the cell surface. The cell membrane of this cell line contains immunoglobulins of M and D classes. RPMI-6410t cells secrete IgM molecules. It is demonstrated that induction of the switch of immunoglobulin heavy-chain classes by the factors of foetal calf serum takes place in the cells of RPMI-6410t line. Thus, the corresponding stage of B-lymphocytes differentiation in vivo is reproduced in 6410t line in vitro. PMID- 3095963 TI - [Changes in the mechanical properties of the epidermis during chemical carcinogenesis]. AB - Effects of the long-term and the short-term action of N-methylurea and 9,10 dimethyl-1,2-benzanthracene on the mechanical properties of the rat epidermis were studied. Both long term and short-term applications were shown to increase the strength of mechanical friction between corneocytes during the whole period of observation, i.e. six and two months, respectively. The increase in the intercellular adhesion in the stratum corneum was proposed to promote the decrease in the cell loss and the tumor growth in the epidermis. PMID- 3095964 TI - [Method of purifying glutaraldehyde for microscopic research on biological objects]. AB - A simple and reliable method of purification and determination of glutaraldehyde concentration for histochemical fixation is proposed. Purification of glutaraldehyde is provided by vacuum distillation with a rotational-filmy evaporator, and its concentration is determined using refractometer. PMID- 3095965 TI - Drug-resistant tuberculosis in Sierra Leone. AB - Culture and sensitivity tests were performed on tubercle bacilli from patients with tuberculosis attending a provincial general hospital in Sierra Leone, who appeared clinically to have drug-resistant infections. Amongst the general intake of patients from 1978 to 1984 there was a 10.5% incidence of isoniazid resistance, with 7.7% of patients having strains resistant to both streptomycin and isoniazid, 1.3% resistant to rifampicin, and 0.8% resistant to ethambutol. Multiple drug resistance was more frequent than single drug resistance. This high incidence is largely due to inadequate and irregular supplies of first line drugs. PMID- 3095966 TI - The Birmingham Tuberculosis Drug Resistance Register, 1956-1983. AB - The findings of the Birmingham Drug Resistance Register are recorded for the years 1956-83. In native born patients initial drug resistance was common up to 1969, but few new cases were discovered after 1970. In the immigrant population a peak of male discoveries was noted in 1968 and a peak of female discoveries in 1979, probably due to immigration patterns. In the native born, single drug resistance was the more common pattern; no initial isoniazid resistance has been detected in this group since 1970. The immigrant patients showed a higher proportion of initial multiple drug resistance. The proportion of culture positive respiratory tuberculosis from which drug resistant bacilli were isolated is given for the years 1976-1983. For native born males this was 1%, for native born females 0.6%, for immigrant males 5.1% and for immigrant females 6.5%. The detections of acquired drug resistance were high in 1956, but since 1970 have fallen to low levels, as has the pool of chronic excretors of drug resistant tubercle bacilli. PMID- 3095967 TI - Enzyme linked protein-A: an ELISA for detection of IgG antibodies against Mycobacterium tuberculosis in intestinal tuberculosis. AB - Enzyme linked protein-A has been used to develop an enzyme-linked immunosorbent assay (ELISA) to detect circulating IgG antibodies to Mycobacterium tuberculosis. The specific binding of protein-A to IgG fractions through Fc receptors, makes the test more specific for detection of total IgG antibodies. The ELISA system has been used for detection of circulating antibodies to M. tuberculosis H37Ra in 22 patients with histologically proven intestinal tuberculosis and 88 healthy controls, in addition to 7 diseased controls. The ELISA has been found to be a sensitive test as it was positive in all 22 patients with intestinal tuberculosis. Its specificity was 85% in Indian controls and 97% in Norwegian controls. The test is easy to perform and may be recommended for the serological diagnosis of intestinal tuberculosis. PMID- 3095968 TI - [(ADP-ribose)n-transferase activity of enterocyte nuclei during radiation injury of small intestine mucosa in rats]. AB - The (ADP-ribose)n transferase activity of enterocyte nuclei of small intestine is studied in rats in normal and under radiation injury of intestine mucosa. It is shown that kinetics of [14C]-NAD incorporation into the acid-insoluble fraction of enterocyte nuclei is of a two-step character when the medium contains 1-15 microM of NAD. The X-ray irradiation of animals (a dose of 0.21 cells per kg) evokes changes in the (ADP-ribose)n transferase activity in nuclei of enterocytes isolated 1-72 h after irradiation. The irradiation results in distortion of the two-step kinetics of (ADP-ribose) synthesis in nuclei. The most pronounced activation of this biopolymer synthesis occurs 1,24 and 36 h after irradiation. In other periods a decrease in the level of (ADP-ribose)n synthesis is observed. Changes in the (ADP-ribose)n transferase activity in nuclei of enterocytes reflect the phase character of radiation sickness course in the small intestine. Activation of these processes is supposed to be a result of intensification of molecular mechanisms of DNA molecule reparation. PMID- 3095969 TI - [Enzyme-forming function of digestive glands after administration of polypeptide C, copepsidyl and panintestine]. AB - Polypeptide C (molecular weight 2640 Dalton) extracted from artificial gastric juice), copepsidyl (containing high dosage of pepsin) and panintestine (polyenzyme drug) are studied for their effect on the activity of digestive enzymes of glandular gastric element pancreas and small intestine of rats. It is established that all mentioned drugs stimulate enzymogenesis in the analyzed organs. The activity of pepsin increases in homogenates of gastric mucosa, the activity of trypsin, total proteinases, carboxypeptidase and amylase grows in pancreas homogenates, and that of leucineaminopeptidase--in small intestine. PMID- 3095970 TI - [Buserelin (Suprefact)]. PMID- 3095971 TI - [The gonococcal antibody test (GAT) as a diagnostic aid. When can GAT be employed?]. PMID- 3095972 TI - [Irregular blood type antibodies in parturient patients in a regional hospital. Has the increased number of abortions resulted in an increase in occurrence]. PMID- 3095973 TI - Cerebral vasoreactivity and arterial gas embolism. AB - Compression regimens effect redistribution of entrapped cerebral arterial gas emboli by reducing embolus length and/or by increasing local perfusion pressure. Embolus length is related to embolus volume and vessel diameter. It has been assumed without evidence that cerebral arterial gas emboli induce local vasoparalysis and hence that the relevant vessel diameter will not be affected by the treatment regimen. This study tested that assumption. Infusion of gas microbubbles into the femoral artery of upright rabbits caused significant but transient hypertension, respiratory depression, cardiac bradyarrythmia, inhibition of cerebrovascular autoregulation to blood pressure changes, and cerebral arterial gas embolism, with entrapment of long emboli in arterioles of 50-200 micron diameter. Cerebral arterioles constricted and dilated appropriately with sequential changes in ventilation gas mixture both before and after gas embolism. The study demonstrated that cerebral arterial gas emboli did not necessarily inhibit cerebrovascular reactivity and that the effect a compression regimen has on cerebral arteriole diameter should be included in any assessment of its efficacy. PMID- 3095974 TI - Ionic basis of short-circuit current in toad skin at high hydrostatic pressure. AB - The toad skin and urinary bladder are widely used for the study of water and Na+ transport under high pressure. These tissues can be mounted in Ussing type chambers and ion transport can be measured by evaluating electrical properties of the preparation, e.g., short-circuit current (Isc). The tacit assumption in these experiments is that the preparation behaves in the same manner at high pressure as at 1 ATA; namely, that net Na+ flux is equivalent to Isc. The purpose of the experiments described here was to test that assumption. Toad skins were mounted in an Ussing chamber and Isc was measured as an index of active net Na+ transport under hydrostatic pressures up to 100 ATA. The chamber was modified so that isotopic Na+ flux from the mucosal to serosal compartments could be measured in conjunction with Isc, without decompression. A linear regression of JNa+ms on Isc was computed and found to be described by the equation, JNa+ms = 3.83 + 0.83 Isc; n = 18; r = 0.92. The slope of the line was not significantly different from unity. No correlation was made for JNa+sm because of the difficulty in measuring JNa+sm and JNa+ms in the same skin simultaneously. Independent measurement of JNa+sm demonstrated that this flux accounted for less than 2% of JNa+net. In a second set of experiments, the influence of amiloride on Isc with and without pressure was tested. 10(-4) M amiloride abolished Isc under both circumstances. It is concluded that Isc can be wholly accounted for by net Na+ flux under pressures up to 100 ATA. PMID- 3095975 TI - [Use of Oxymycoin and Chronicin foam in the nonselective care of udders of dry dairy cows]. AB - The non-selective antibiotic treatment of dairy cows at the last milking in lactation was studied for its influence on the reduction in the occurrence of infectious processes in the udder after calving. The herd of 120 dairy cows, on an average, was housed in the K 98 cow-house and in a calving house equipped with the traditional technology. The non-selective treatment was performed in 125 dairy cows in the form of single administration of Oxymykoin foam (Galena) (70 cows) and Chronicin foam (Galena) (55 cows) after the last milking in lactation. The treatment of 53 bacteriologically positive cows with Oxymykoin foam had 86.8% therapeutic effectiveness; this indicates the excellent effectiveness of the preparation. Five additional new infections arose in this group of cows treated with Oxymykoin. The treatment of 36 bacteriologically positive cows with Chronicin foam had the effectiveness of 63.9%; in almost 2/5 of the treated cows (13 animals) the bacteria causing mastitis persisted in the post-parturient period. Eight new infections occurred in this group of treated cows. The results of the non-selective antibiotic treatment of dairy cows after the last milking in lactation prove the good effectiveness of the method reducing the percentage of infected cows in the period after calving. PMID- 3095976 TI - [Biological, chemical and pathohistologic study of the skin in papular dermatitis in fattened pigs]. AB - We examined the skin samples from 23 fattened pigs with papular dermatitis (PD) and from 17 pigs showing no skin lesions; the live weight of the pigs was from 95 to 105 kg and the pigs came from a large fattening house D that is located in the region where the mines are frequent (lignite extraction). It was only in 26% of pigs with PD where the common ectoparasites Haematopinus suis and Sarcoptes scabiei var. suis were found out. The skin lesions were not fluorescent in the light of Wood's lamp. The fungi Aspergillus flavus, A. fumigatus, A. tereus, Chrysosporium, Mucor sp., Scopulariopsis sp. were sporadically isolated from the skin lesions in 39% of pigs with PD. In 65% of pigs with PD Staphylococcus aureus was isolated from the skin lesions, which was not found in pigs without dermal lesions. Staphylococcus epidermidis was isolated in 87% of pigs with PD and 58% of pigs without any skin changes. The skin lesions were virus-free. Increased concentrations of cadmium and mercury were observed in the skin of pigs with PD and in control pigs. The concentration of aflatoxin B1 in the skin of the two groups of pigs did not exceed the level of 5 micrograms X kg-1, in PD pigs it was, however, twice higher than in the clinically healthy pigs. The residues of chlorinated hydrocarbons in the subcutaneous fat were not higher than the certified hygienic levels. Both epidermis and corium are affected by inflammatory lesions. At the beginning, neutrophil infiltration with necrotization of epithelial cells prevails. It is followed by capillary proliferation with angioblast and fibroblast multiplication and straggled lymphoid infiltration. It is necessary to distinguish by differential diagnostics: swine pox, parakeratosis of swine, lesions of impetigo contagiosa suum, pustular dermatitis and scab of swine, and from rarely occurring skin diseases of swine hypotrichosis cystica suis and demodicosis of swine. No conclusions can be drawn explicitly on the etiology and pathogenesis of papular dermatitis in fattened pigs. We must study the potential interactions of negative environmental factors with regulating homeostatic and adaptation mechanisms in fattened pigs. PMID- 3095977 TI - [Incidence of Toxoplasma gondii oocysts in cat feces]. AB - Within two years and a half, the faeces of 620 cats coming from Brno and the area around the city were subjected to parasitological examination with special regard to the occurrence of the oocysts of Toxoplasma gondii. Sucrose solution at the specific weight of 1,150 was used as flotation medium. Oocysts of Toxoplasma gondii were eliminated by eight cats (1.29%) at the age from 16 days to 1.5 years. Six of the eight cats were younger than seven months. The Toxoplasma gondii oocysts were eliminated by the cats for 1-16 days while exhibiting signs of short-term scours and swelling of lymph nodes. In all cases the oocysts of Toxoplasma gondii were produced in the summer and autumn seasons (June-December). During the patent period, other coccidia (Isospora felis and Isospora rivolta) were also present in the cats. PMID- 3095978 TI - [Androgenic aspects of estrogens]. AB - There is a literature review of the origin of oestrogens in male organisms, of the occurrence of oestrogens in the blood, urine and ejaculate of boars, of the importance of oestrogens in the endocrine regulation processes in males, and the role of oestrogens in relation to the sexual activity of males. It is emphasized that, as suggested by the latest findings, the exclusively antagonistic concept of the function of androgens and oestrogens is overcome, having given way to the aspect of synergism of these sex hormones and their physiological role in both sexes. PMID- 3095979 TI - Use of bovine lymphocyte antigens in diagnosis of parentage. AB - Lymphocyte antigens controlled by alleles at the BoLA-A locus were used to indicate which of two bulls could be eliminated as the sire in 18 cases of disputed parentage. The use of bovine lymphocyte antigens (BoLA) significantly increased the exclusion probability over that of the standard red cell and electrophoretic techniques. PMID- 3095980 TI - Humoral antibody response of rabbits to experimental infection with Encephalitozoon cuniculi. AB - Six female rabbits (Oryctolagus cuniculus) were experimentally infected intravenously with approximately 1.5 X 10(7) live spores of Encephalitozoon cuniculi. Head tilt was observed as the single clinical sign in only one of the six animals. Antibody response was registered over 68 days postinfection using the indirect immunofluorescence test (IFT) for IgM and IgG, and the carbon immunoassay (CIA). IgG titers reached a level of 160-2560 after a latent phase of 13-28 days, followed by a 2-4 week relatively steep increase. The IgM seroconversion was faster than that of IgG and occurred at the beginning of the antibody response. Thus, simultaneous detection of both IgM and IgG allowed the infection to be identified as recent. Long, short, and episodic antibody responses could be distinguished: the IgG titer continued to increase on Day 68 in one animal (long response) and began to decrease between Days 45 and 63 in three other animals (short response). In two additional animals the seroconversion was very short, occurring between Days 13 and 41, and 28 and 52, respectively (episodic response). The CIA proved to be specific, reliable, and simple to perform; titers were slightly higher than in the IFT. Parasite pseudocysts were detected scattered throughout the brain on Day 68 in four of the six rabbits. The persistence of antigen in the brain did not correlate with antibody response, which in most cases was shorter. PMID- 3095981 TI - Biochemical and histochemical studies of the sarcocyst of Sarcocystis fusiformis of buffalo Bubalus bubalis. AB - The glycogen content and activities of alkaline and acid phosphatases of sarcocysts of Sarcocystis fusiformis from naturally infected Indian water buffalo (Bubalus bubalis) were determined biochemically and histochemically. PMID- 3095982 TI - Discontinuous counter-immunoelectrophoresis test for detection of Trypanosoma evansi antibody in buffalo calves and its comparison with agar gel precipitation test. AB - Discontinuous counter-immunoelectrophoresis was used to detect Trypanosoma evansi antibodies in experimentally-infected buffalo calves. The method was found to be simple, reproducible, rapid and sensitive. Results could be read within 15 min and compared favourably with results obtained with the agar gel precipitation test. PMID- 3095983 TI - Interaction of the bacteriophage phi 29 connector protein with the viral DNA. AB - The protein that forms the connector of phage phi 29, p10, binds to DNA. Apparently, p10 binding is not sequence specific. Nevertheless, the presence of the terminal protein (p3) covalently attached to the ends of phi 29 DNA produces a significant increase of p10 molecules bound to the DNA ends, thus suggesting a terminal protein-mediated recognition of DNA ends by the phage connector. As the p3-DNA complex is the substrate for phage phi 29 DNA packaging, these results may reflect a direct implication of the phage connector in the packaging process. PMID- 3095984 TI - [Present status of Tsutsugamushi disease, especially its epidemiology, clinical features and etiological diagnosis in Japan]. PMID- 3095985 TI - [Biochemical diagnosis of Anderson-Fabry disease in two brothers]. AB - Activity of several lysosomal enzymes was studied in leukocytes, blood plasma and skin fibroblasts of two adult brothers with clinical diagnosis of Fabry disease. Activity of ceramide trihexoside-galactosidase was distinctly decreased in both patients. The residual enzymatic activity constituted 5-6% in the patients leukocytes, less than 10% in blood plasma and 25% in fibroblasts as compared with controls. Differences in composition of alpha-D-galactosidase multiple forms were detected in fibroblasts and blood cells of the patients with Fabry disease as compared with normal leukocytes by means of isoelectric focusing. PMID- 3095986 TI - [Interaction of glycosaminoglycans with positively charged fluorochromes]. AB - Interaction of glycosaminoglycans (GAG) with cationic fluorochromes, which are used for binding with DNA, was studied in biological material (urine, extract from hyalin cartilage) obtained from patients with hereditary mucopolysaccharidoses and from healthy persons. Among the four fluorochromes studied in the reactions with standard GAG's, DAPI proved to be the most suitable fluorochrome. Quantitative fluorimetric technique enabled to estimate the GAG concentration and to evaluate the individual content of heparan-SO4 and keratan SO4 in biological sources. Interaction of DAPI with GAG was electrostatic and depended on stereometry of DAPI-binding sites on the GAG molecule. PMID- 3095987 TI - Pulmonary reaction associated with transfusion of plasma containing anti-5b. AB - A patient developed an acute respiratory distress syndrome with lung infiltrates during a transfusion of plasma. The transfused plasma was shown to contain a potent leucocyte agglutinating antibody of IgG type with anti-5b specificity, reactive with the patient's cells. A review of the literature on similar transfusion-related syndromes showed an association with more of less well defined white cell antibodies, mainly in the donors' plasma. The majority of donors were multiparous women. The anti-5b in our donor was demonstrated only by granulocyte agglutination technique, as previously described antibodies in the five system. A long incubation procedure (20-25 h) seemed to be optimal for granulocyte agglutination. PMID- 3095988 TI - Hemolytic anemia due to a mixture of low-titer IgG lambda and IgM lambda agglutinins reacting optimally at 22 degrees C. AB - A 65-year-old white man had severe hemolytic anemia due to a mixture of low-titer IgG lambda and IgM lambda agglutinins showing optimum reactivity at 22 degrees C. The IgG agglutinins were detected by manual indirect antiglobulin test (IAT) using anti-IgG, and had a titer of 1 at 37 degrees C, 128 at 22 degrees C and 16 at 4 degrees C against adult type O red blood cells (RBC). The corresponding titers with cord RBC were 1 (37 degrees C), 64 (22 degrees C) and 8 (4 degrees C). Proteolytic enzyme and neuraminidase treatment of RBC did not decrease these titers. No known specificity could be assigned to these agglutinins. The isolated agglutinins (recovered by cold adsorption, warm elution) were shown by immunoelectrophoresis to be IgG lambda antibodies. They did not bind complement in vitro, consistent with the finding that the patient had negative manual direct antiglobulin test (DAT) by anti-C3d. It could be shown only by automated IAT that patient's serum also contained IgM cold agglutinins which also reacted best at 22 degrees C and appeared to be of lambda light-chain type. The patient responded to corticosteroid therapy and remains well without treatment 14 months after the hemolytic episode. The presence of IgG cold agglutinins may be predictive of a favorable response to corticosteroid therapy. PMID- 3095989 TI - Fetomaternal transplacental hemorrhage during pregnancy and after delivery. AB - One third of very weakly Rh-immunized women show no increase in their level of Rh immunization during pregnancy and after delivery. Administration of 300 micrograms of Rh immune globulin at 6-week intervals does not alter the incidence of lack of progression of Rh immunization in such women. Thirty-three Rh-positive women who ultimately delivered ABO-compatible babies, had Kleihauer fetal transplacental hemorrhage (TPH) screening tests carried out at 2-week intervals during pregnancy and shortly after delivery. One third of the 33 women had no detectable TPH or a TPH of 0.01 ml of fetal red cells. We conclude that one third of weakly Rh-immunized women failed to show any progression of their Rh immune response during pregnancy or after delivery because they were exposed to too few fetal red cells (0.01 ml or less) to produce such a response. PMID- 3095991 TI - WHO Expert Committee on Venereal Diseases and Treponematoses. Sixth report. PMID- 3095990 TI - A study of IgE in immunoglobulin preparations for intravenous administration. I. IgE in intravenous IgG. AB - We have studied the IgE content of different lots of commercial intravenous IgG preparations used in our day hospital as replacement therapy for patients with agammaglobulinemia. Two enzymatic methods were used: Phadezym and FAST. The average amounts of IgE detected in Endobulin and Sandoglobulin lots were very high with respect to serum values in the general population. In some lots we found low titers of specific IgE (RAST class 1) to house dust mite, rye grass and cow's milk. We also found in most preparations the presence of IgG anti-IgE which are usually present in sera from atopic patients. Despite a low post-infusion increase of serum IgE and the absence of sensitization or adverse reactions observed, a careful selection of donors with normal IgE levels may need to be recommended to manufacturers in the future. PMID- 3095992 TI - The endocrine function of heterotopic islets of Langerhans. PMID- 3095994 TI - [Some aspects of the evaluation of protein requirements and protein supply in developing countries]. PMID- 3095993 TI - Diverticula of the mid- and lower esophagus: pathogenesis and surgical management. PMID- 3095995 TI - [Current status and the development of resistance of important urinary pathogens to antibiotics in the Suhl district 1970-1984]. AB - In a retrospective study over a period from 1970 to 1984 the distribution of frequency and the behaviour of the resistance of urine germs out of more than 43,000 sendings from outpatient and hospital institutions of the county of Suhl were analysed. In the period of observation the proportion of isolated E. coli redoubled and was nearly 68% in 1984. Conspicuous were a decrease of the isolates of Str. faecalis from 32 to 4% and an increase of problem germs of the Klebsiella group to 9.7%. The resistance situation is characterized by a distinct decrease of the resistance of E. coli in comparison to antimicrobial substances with smaller consumption (sulphonamides, chloramphenicol, nitrafurantoin) without homogeneous behaviour of the problem germs. PMID- 3095996 TI - [Experimental and clinical organ transplantation. Charite-Symposium 1985. Berlin, East Germany, 16-20 September 1985]. PMID- 3095997 TI - [Heart-lung transplantation without extracorporeal circulation. A new animal model for research on heart and lung preservation]. PMID- 3095998 TI - [Early diagnosis of the acute rejection reaction and infections in the peripheral blood of patients after heart and heart-lung transplantations]. PMID- 3095999 TI - [Scintigraphic demonstration of transplanted hepatocytes in the spleen and liver]. PMID- 3096000 TI - [Our experiences with pancreas transplantation in diabetic patients]. PMID- 3096001 TI - [Influence of the pancreas transplantation technic on islet morphology, long-term function and the rejection process in inbred rats]. PMID- 3096002 TI - [Prolongation of the survival time of islet allografts in the Lewis rat system by culture technics or PUVA pretreatment of the isolated islets]. PMID- 3096003 TI - [Immunogenetic aspects of the transplantation of isolated islands of Langerhans]. PMID- 3096004 TI - [Transplantation of pancreatic islets in dogs--a new method]. PMID- 3096005 TI - [Release of pancreatic polypeptide and insulin after autotransplantation of the pancreas in dogs]. PMID- 3096006 TI - [Purification procedure for allogenic 125iodine-labeled anti-human factor VII:C IgG by polyacrylamide gel disc electrophoresis for use of factor VIII:CAg radioimmunoassay]. PMID- 3096007 TI - [Apolipoprotein D, isolation and development of its electroimmunoassay]. PMID- 3096008 TI - [Immunoturbidimetric determination of IgG, IgA,, IgM and haptoglobin with the SPEKOL 21: a comparison of methods using radial immunodiffusion and laser nephelometry]. PMID- 3096009 TI - [Demonstration of autoantibodies to "extractable nuclear antigens" with the Ouchterlony test, counterimmunoelectrophoresis and enzyme immunoassay in comparison with the immunofluorescence test]. PMID- 3096010 TI - Arvicola terrestris, Linnaeus 1758, a reservoir of Pneumocystis sp. Delanoe and Delanoe 1912. PMID- 3096011 TI - [Effect of long-term lithium treatment on serotonin syndrome in rats]. AB - Brain 5-HT receptors are reported to play an important role in the therapeutic effect of Li in manic-depressive illness. In the present study we examined the effect of Li on 5-HT syndrome which is postulated to be the physiological response of 5-HT1 receptors. Intraperitoneal injection of the 5-HT receptor agonist 5-MeODMT elicited 5-HT syndrome in a dose-dependent manner. Then the incidence of 5-HT syndrome elicited by 2 mg/kg of 5-MeODMT was measured in animals under long-term Li treatment. Four out of six abnormal behaviors of the 5 HT syndrome, i.e. forepaw treading, resting tremor, rigidity, and head weaving, were significantly increased by the 9-day treatment with Li. On the 17th day of Li treatment, the incidence of all six behaviors, including hindlimb abduction and straub tail, were significantly enhanced. This Li-induced supersensitivity of 5-HT1 receptor-mediated behaviors inconsistent with the previous reports of the down-regulation of 5-HT1 receptors measured by receptor binding assay. The reason for this discrepancy is obscure. Further examination of the effect of Li on the signal-transduction system from the receptor to the behavior will be necessary. PMID- 3096012 TI - [Effect of DN-1417 on ataxia in Rolling mouse Nagoya and Staggerer mouse in comparison with the effect of TRH]. AB - The behavioral effects of thyrotropin-releasing hormone (TRH) and a TRH analogue, DN-1417 (butyrolactone-carbonyl-L-histidyl-L-prolinamide citrate) on the ataxia of Rolling mouse Nagoya and Staggerer mouse were examined using open-field methods. The ataxic gaits improved after injection of TRH (25 mg/kg, ip) and DN 1417 (5.25 mg/kg ip), compared with injection of saline. As a whole, the improving effect of DN-1417 persisted about 2 or more times as long in duration as that of TRH. PMID- 3096013 TI - Evidence for antibacterial substances in diets for laboratory animals. PMID- 3096015 TI - Cadmium concentrations in autopsy material from differently polluted areas of West Germany (FRG). AB - Analyses of Cadmium (Cd) in human specimens demand special interest since the Federal Environmental Agency of West-Germany (UBA, FRG) has published calculations and high figures of renal disturbances due to Cd. We analyzed autopsy material from the Cd-polluted area of Goslar/Harz Mountains (N = 28) and from the less contaminated region Erlangen/Nurnberg (Franconia) (N = 50). As determinants of Cd-concentration special regard was given to age, smoking habits, residence (urban/rural), and medical findings (nephropathy, hypertension). A balanced distribution of age is found in all subdivisions, the mean age of death is 66 and 68 yrs., respectively, in both regions. Median values of Cd concentrations in the target organs from Franconia were found to be half the amount of those from Goslar (renal cortex: 12/19, medulla: 8/16, liver: 1/3 micrograms Cd/g wet weight). Significant local differences are found for renal medulla and liver (p less than 0.05). In both regions the Cd-content is independent from sex and residence (urban/rural). The influence of tobacco smoking on the Cd-burden is evident (greater than 50%). Cases of hypertension show maximum values, although this trend can't be confirmed by the median values. Regional Cd-pollution seems to have more effect than pathological findings: normotensive persons from Goslar have higher median renal Cd-concentrations than hypertensive patients from Franconia. Analyses of renal diseases reveal the same result. All Cd-concentrations are far below the critical value (200 micrograms Cd/g renal cortex, w.w.). The evaluation of such limit values and the results of similar studies are briefly discussed. PMID- 3096014 TI - Essential fatty acid patterns in preeclampsia. AB - Fatty acid patterns were determined for maternal and cord sera from normal and preeclamptic pregnancies using gas liquid chromatography. Ten normal and 11 preeclamptic maternal sera were used; 6 preeclamptic and 6 normal cord sera were measured. Fatty acid patterns were measured in the nonesterified fatty acids (NEFA), the triglycerides (TG), the cholesterol esters (CE), and the phospholipids (PL). Preeclampsia showed significant differences in the essential fatty acid patterns in the maternal and cord sera compared to normal pregnancy. Oleic acid, an early indicator of essential fatty acid deficiency, made up a significantly greater proportion of preeclamptic cord blood NEFA, TG, and PL than in normal cord blood. Abnormalities in essential fatty acid patterns may be associated with decreased prostacyclin production and dysmaturity which may be seen with preeclampsia. PMID- 3096016 TI - [Pentachlorophenol concentrations in the organs and blood of 11 dead infants]. AB - For 11 children, died on age between 2.5 and 57 month due to different causes, the concentrations of pentachlorophenol in liver, kidney, brain and blood were located in the lower part of the spread of test values found for adults which had died in the same region and during the same time phase. The concentrations of pentachlorophenol in the blood of the 11 children were compared further with the findings from 20 living children with an age up to 10 years and were all located below the median of the test values (45,4 micrograms PCP/1) from the group last mentioned. There are no hints for connections between the body-burden of pentachlorophenol and the death-cases concerning the 11 children. PMID- 3096017 TI - [The effect of a weak magnetic alternating field on immunobiologic reactions]. AB - The influence of a 10 Hz, 0.5 mT (millitesla) alternating magnetic field (rectangular function) on immunologic parameters was investigated. In four chambers, each containing 15 mice, the following electroclimatic conditions existed: conventionally air conditioned laboratory (L), screening of the ambient atmospheric electric fields (F), Faradayscreening plus the above mentioned magnetic field (F + M) and the magnetic field only (M). After 14 days of acclimatizing without magnetic field influence the mice were exposed to the field in the chambers F + M and M for 1, 3, 7 and 21 days, respectively. At the end of the exposure immunological reactions were examined. METHODS: Plaquetest (hemolysis in gel) according to Jerne et al. and determination of the hemagglutination titer. The different groups (L, F, F + M and M) were compared using the Student-t test or variance analysis. RESULTS: After 7 days of field exposure the plaquecount and the hemagglutination titer (converted into the logarithm of base 2) increased significantly in comparison to the controls (L and F, respectively) in some experiments. In experiments carried out with 3 and 21 days of exposure the same tendency (increase of immunological reaction) was detected. PMID- 3096018 TI - Post-mortem bacterial culture of bronchial mucus and heart blood in hospital and non-hospital autopsies: effect of morgue time and length of hospitalization. AB - We studied cultures of 109 bronchial mucus and 67 heart blood specimens from unselected hospital autopsies and 40 bronchial mucus and heart blood specimens from unselected non-hospital (forensic) autopsies, performed 1-11 days after death. The most prevalent bacterium was Streptococcus viridans. No association was found between morgue time and the number of species isolated from each bronchial mucus or heart blood specimen in either hospital or non-hospital autopsies, nor between morgue time and the number of occasions different species were isolated from the bronchial mucus or heart blood specimens in either series. Bronchial mucus and heart blood cultures from the hospital autopsies gave more often gram negative rods and less often other microbes in result than those from the non-hospital autopsies (p less than 0.05 and p less than 0.025 respectively). There was a highly significant association between the length of hospitalization and the occurrence of gram negative rods both in the bronchial mucus and heart blood (p less than 0.001 and p less than 0.0001 respectively), a result which probably reflects the ante-mortem colonization of the respiratory tract with gram negative bacilli among hospitalized patients. PMID- 3096019 TI - [Germicidal experiments with aqueous PVP-iodine-containing disinfecting solutions: effect of the content of free iodine on the bactericidal action against Staphylococcus aureus]. AB - The bactericidal activity against Staph. aureus of three PVP-iodine preparations in different concentrations, and of 0.1 mol/L KI-solutions with concentrations of free iodine corresponding to the povidone-iodine preparations, was evaluated at reaction times of 7, 15, 30 and 60 seconds. The concentration of free iodine has been measured potentiometrically during the entire reaction time. In all cases it has been confirmed that the bactericidal activity is increasing with the concentration of free iodine. However, there have been found differing correlations between the logarithmic decrease of germs (RF-value), the concentration of free iodine and the reaction time (statistical evaluation of the results by means of linear multiple regression: RF = a0 + a1 log [I2] + a2 log t). Referring to the concentration of free iodine the bactericidal activity in the range of RF approximately equal to 4-6 is increasing as follows: Povidone iodine washing concentrate much greater than iodine in KI (0.1 mol/l) greater than Povidone-iodine mucosal disinfectant greater than aqueous solution of povidone iodine. This sequence is explained by differences of composition. So it is assumed that the surface active ingredients facilitate the penetration of molecular iodine. The observed correlations show that there is probably no exact mathematical relation of general validity for iodine preparations of different composition between the concentration of free iodine and the RF-value. However, for one and the same preparation such a correlation can be derived and enables to make predictions about the bactericidal activity, which can be expected as a consequence of the concentration of free iodine. PMID- 3096020 TI - Relationship between environment spread and presence in hosts of Escherichia coli strains resistant to antibiotics and metals. AB - The antibiotic and metal resistance percentages of 315 E. coli strains, isolated from: a sample population not-exposed to antibiotics, hospitalized inpatients and from bred animals, were compared with the resistance percentages of 217 environmental isolates (sewage and river isolates). The highest levels of resistance and multiresistance were found for clinical and river isolates. A wider number of resistance markers, observed for environment isolates with respect to human and animal isolates, made it possible to hypothesis e that the resistant strains could possess some selective advantage that enhances their survival in the environment. Association of antibiotic resistance and metal resistance has been demonstrated in all isolates but it is particularly evident in the environment and clinical isolates. Correlation analysis revealed that the patterns of antibiotic and metal resistance of environmental E. coli isolates are in good agreement with those of human origin and that sewage and river E. coli isolates are well correlated too. PMID- 3096021 TI - Phagetypes of human and bovine Streptococcus agalactiae isolates in Slovenia. AB - In two rural areas 34 human (colonization) and 2 bovine (mastitis) Str. agalactiae strains were isolated. Identical serotypes and phagetypes in persons and cows were established: serotype R with phagetype 14/27/30/31 in two persons and one cow from two neighbouring villages, and serotype Ic with phagetype 4/12/16/18/20 in a child and a cow from the same household. Identical serotypes and phagetypes were also found in two married couples and in members of other families. Serotypes with phagetypes confirm the transmission of Str. agalactiae from person to person, but also show, that the transmission from cows to humans might be possible. PMID- 3096022 TI - Computer analysis of some bacteriological, biological and physiochemical parameters of the coastal water of Lake Balaton. AB - Some 61 coastal water samples were taken at four definite points of Balaton Lake. Seventeen parameters of each sample characterizing the quality of the water were studied by means of multiple correlation and regression analysis, one-way variance analysis and by factor analysis with the help of BMD computer program. Uni- and multilateral relationships could be observed among the single parameters. On the basis of the results of factor analysis six factors- phytoplankton system, anthropogenic effect, own bacterial system of the lake, nitrogen circulation, hydrocarbonate and reactive phosphate system and NH+4 circulation--could be separated. Significant qualitative differences could be found along the longitudinal axis of Balaton. It could be also demonstrated that the water of the lake in its present condition is suitable for the proliferation of bacteria. Further and deeper examinations are necessary for a better understanding of the biochemical and biological processes. PMID- 3096023 TI - [The ATP concentration of drinking water compared to the colony count]. AB - During a four months' period we have monitored the drinking water of the city of Berlin for its ATP-content and for its Total Colony Count. After concentrating the drinking water by a factor of 1000 by filtration, we obtained ATP-values which were always significantly above the blanks. The profile of the ATP-values roughly paralleled that of the Colony Counts; however, as we never observed Colony Counts nearly approaching 100 colonies/ml (which is the value not to be exceeded according to current German Law), we are unable to positively assess how the ATP-value would have behaved in samples with Colony Counts above 100 ml. Analysis of increasing dilutions of sewage tested for both Colony Counts and ATP indicate that values above 100 colonies/ml would have yielded ATP-values well above those normally seen in drinking water. Therefore, ATP could probably be taken as a measure for the Total Colony Count. PMID- 3096024 TI - [Pathophysiology of inappetence. 1. Inappetence as a sequela of the activation of gastrointestinal and metabolic feedback signals]. PMID- 3096025 TI - [Pathophysiology of inappetence. 2. Inappetence as a sequela of learned taste aversions]. PMID- 3096026 TI - Concentration of some important elements in the liver of young cattle supplemented with selenite enriched feed. PMID- 3096027 TI - [Cardiotocographic findings in healthy and asphyxiated cattle fetuses in the 2d stage of labor]. PMID- 3096028 TI - Rectovaginal constriction (RVC) in Jersey cattle: VI. Immunohistochemical studies of collagen. PMID- 3096029 TI - [Involution of the mammary gland in goats. Histological and histochemical studies at various times following drying out]. PMID- 3096030 TI - [Analysis of the ventricular electrical systole of sheep. II. Repolarization]. PMID- 3096031 TI - Immunizing activity of oil adjuvant attenuated spore vaccine of Bacillus anthracis in sheep. PMID- 3096032 TI - [Diagnosis and clinical manifestations of dental plexalgia]. AB - The article considers characteristics of clinical manifestations of dental plexalgia, a new form of the disease related to impairment of dental plexuses. In a clinicophysiological study of 56 patients with dental plexalgia conducted at a neurostomatological department the authors used rheofaciography, thermometry and thermography of the face skin, esthesiometry, and electrodiagnosis of the oral mucosa. Electrodiagnosis of the oral mucosa helps to specify the diagnosis of dental plexalgia. The authors describe differential diagnosis criteria reflecting the peculiarities of the clinical picture of dental plexalgia which is characterized by the persistent pain in the area of the damaged plexus with peculiar irradiation which may be used for the diagnosis, rational etiopathogenetic therapy, prophylaxis, and prognosis of the disease. PMID- 3096033 TI - [Use of lithium carbonate and vitamin E in the complex treatment of epileptics]. AB - Using clinico-biochemical and EEG examinations, the authors have studied over time 30 epileptic patients who along with anticonvulsants received lithium carbonate orally and vitamin E in injections. Before the administration of the above drugs epileptic patients with a progressive course of the disease showed intensified lipid peroxidation, low levels of total and free cholesterol of erythrocyte membranes, elevated concentrations of vitamin E and a decreased activity of superoxide dismutase (SOD) in the blood. The use of lithium carbonate and vitamin E leads to a considerable decrease in lipid peroxidation, an elevation in the content of total and free cholesterol of red cell membranes and an increased SOD activity in the blood. There was also a considerable improvement in EEG parameters. The above positive changes in paraclinical indices were accompanied by a reduction in the frequency of epileptic attacks and affective calming of patients. The authors believe that the obtained results can be explained by the normalization of the cell membrane permeability and recommend that lithium carbonate and vitamin E be included into the array of anticonvulsive drugs. PMID- 3096034 TI - Effects of thyrotropin-releasing hormone and cyclo-histidine-proline on the homeothermic development of neonatal rats. AB - The effects of thyrotropin-releasing hormone (TRH) and its putative metabolite, cyclo-histidine-proline (cHP), on the homeothermic development of neonatal rats were studied. The daily intrathecal administration of 10(-11)-10(-9) moles of TRH during the second week of age produced a significant rise in body temperature by 3 weeks of age and was followed by a transient period of hypothermia. This effect, which could not be produced by an intraperitoneal injection of 10(-7) moles of TRH, was abolished by the simultaneous administration of 6 hydroxydopamine (6OHD). In contrast, intrathecally administered cHP decreased thermogenesis. During TRH treatment, brain norepinephrine (NE) and dopamine (DA) release was accelerated 2- to 4-fold. Two weeks after either TRH or cHP treatment, brain NE and DA were significantly reduced; adrenal NE in cHP-treated rats increased. The weight of the interscapular brown adipose tissue (BAT) was decreased by both cHP and 6OHD. At 3 weeks of age, [3H]guanosine diphosphate binding capacity in BAT mitochondria was reduced by 60% in TRH-treated rats and was associated with reduced mitochondrial levels of alpha-glycerophosphate dehydrogenase and liver cytochrome C reductase. These results indicate that TRH stimulates central NE release thereby enhancing thermogenesis, cHP decreases heat production, and TRH-induced hyperthermia is associated with changes in mitochondrial exothermic processes. The central TRH-cHP system may modulate the maturation of homeothermic mechanism in neonatal rats. PMID- 3096035 TI - Influence of terbutaline on TRH-induced prolactin and thyrotropin release in normal subjects. AB - To investigate whether terbutaline (T) influences the release of prolactin (Prl) and/or thyrotropin (TSH) from the anterior pituitary, 25 micrograms thyrotropin releasing hormone (TRH) was injected iv in 7 normal subjects who were pre-treated orally with either T or placebo. The TRH-induced Prl response, as reflected by the Prl incremental area, was more pronounced after priming with placebo (2071 +/ 606) than after T (1391 +/- 434; P less than 0.05). In contrast, the TRH elicited TSH responses did not differ significantly after the two pre-treatments. When TRH was given to 8 additional individuals on iv background infusion of either T or saline, the Prl response was significantly larger during saline (2123 +/- 354) than during T infusion (1540 +/- 235; P less than 0.01), whereas the TSH responses were of similar magnitudes. Six subjects, given 25 micrograms TRH iv on background infusion of T or saline, were also given propranolol orally before commencement of the T infusion and placebo before the saline infusion. This resulted in similar Prl responses and also in similar TSH responses, during the two background treatments. The results imply that oral as well as iv administration of T has inhibitory influence on human lactotrophs, but lacks measurable effect on thyrotrophs. PMID- 3096036 TI - Single and repeated testing of growth hormone secretory capacity in hypopituitarism using growth hormone releasing factor. AB - 38 patients with proven growth hormone deficiency (GHD) and 19 children with familial short stature received an iv GRF-bolus injection of 1 microgram/kg body weight. Whereas in all control children plasma growth hormone rose significantly (mean of maximal values 36 ng/ml), only 7 out of 38 patients with GHD reached peak values of 8 ng/ml or more. GRF-priming by 1 microgram GRF/kg BW given once daily s.c. for 5 days in 19 patients improved the response of the pituitary gland in 11. Thus, following the first GRF test, only 21% of patients demonstrated function of the pituitary gland whereas 45% did so when all test results are combined. To evaluate the pituitary function in patients with GHD correctly, GRF tests following a GRF priming period seems to be necessary to reactivate atrophic somatotropic cells of the pituitary gland. PMID- 3096037 TI - Growth hormone-releasing hormone in the diagnosis and treatment of growth hormone deficient children. AB - A growth hormone-releasing hormone (GHRH) has recently been extracted and synthesised, and appears to be identical to human hypothalamic GHRH. Immunoreactive GHRH is found in the venous blood of normal subjects and GH deficient children, but is probably not hypothalamic in origin and therefore not important in GH regulation. GHRH is a potent specific stimulator of GH secretion in man, and provides a valuable diagnostic test in differentiating hypothalamic from pituitary causes of GH deficiency. Preliminary data suggests that GHRH may promote linear growth in some GH deficient children. GHRH may well prove an important alternative therapy for GH deficient children especially if depot preparations or intranasal administration prove effective. PMID- 3096038 TI - Hypothalamic GnRH-like bioactivity and immunoreactivity in prepubertal and adult male rats. AB - In prepubertal (21-days old) and adult (50-days old) male rats, the immunological and biological properties of GnRH-like material extracted from the hypothalamus were studied. At both ages, hypothalamic material and synthetic GnRH resulted in a parallel inhibition of the binding of labelled GnRH to 2 different anti-GnRH antisera (As I and As II). Using both antisera, a similar amount of immunoreactivity was measured in several extracts from 50-day hypothalami. In contrast, hypothalamic extracts obtained at 21 days contained a greater immunoreactivity using As II than using As I. This discrepancy was only observed with the hypothalamic content whereas the immunoreactivity released in vitro was similar with the two antisera at both ages studied. Filtration of hypothalamic extracts on biogel P2 revealed two immunoreactive fractions, the major one being eluted as the synthetic decapeptide and showing a similar immunoreactivity using both antisera. A high molecular weight fraction was proportionally predominant in 21-day extracts and showed a greater immunoreactivity using As II than using As I. The biopotency of the hypothalamic extracts upon rat pituitary cells in vitro was similar at the two ages but around 30 times higher than the bioactivity expected for the immunoreactivity. We conclude that the heterogeneous physicochemical and immunological nature of hypothalamic GnRH is different before and after sexual maturation in the male rat, whereas the bioactivity, although much greater than expected, is similar at both ages. PMID- 3096039 TI - Why do children with diabetes die? AB - While the treatment of children with Type I diabetes mellitus has dramatically improved since the introduction of insulin in 1922, significant acute mortality still remains. To better ascertain the causes of death in younger children and adolescents with diabetes mellitus, a retrospective review was undertaken of diabetes associated mortality in the patient population followed at the Children's Hospital of Pittsburgh between the years 1950 and 1985. Fifty-five deaths were identified of which 20 occurred during the initial presentation of diabetes and 35 occurred between 2 months and 11 years following the diagnosis of diabetes mellitus. Diabetic ketoacidosis (DKA) was associated with 64% of the total mortality with 85% of the early onset and 54% of the late onset deaths being ketoacidosis related. Of these ketoacidosis associated deaths, cerebral edema was documented in 31%, or 20% of the total group mortality. Non ketoacidosis deaths in both early and late onset groups were caused by heterogeneous events. There were no deaths associated with the traditional late vascular complications of diabetes mellitus. Since diabetic ketoacidosis is a potentially preventable acute complication of diabetes mellitus and represented a predominant cause of mortality in these children, early recognition and prompt treatment might substantially reduce childhood mortality in patients with Type I diabetes mellitus. PMID- 3096040 TI - Thyroid function in prematures with respiratory distress syndrome (RDS). AB - Reports on thyroid function in newborns with respiratory distress syndrome (RDS) are controversial, the significance of obtained results is not clear. Therefore we conducted a longitudinal study of thyroid function in 35 infants with RDS (gestational age 24-36 weeks, birth weights 650-2770 g). 43 well prematures, matched for gestational age, served as controls. No significant differences were observed in cord blood TSH, T3, T4, TBG values and T4:TBG ratios between infants with and without RDS. Prematures with RDS showed lower levels of T3, T4, TBG and T4:TBG at 24 hours of age and increases of TSH values at 72 hours. Subsequently these prematures exhibited a spontaneous rise in thyroid hormone levels. Even non surviving RDS-infants had initial T3, T4, T4:TBG and TSH values within the normal range. Thyroid hormone concentrations correlated significantly with the severity of pulmonary disease. Depressed thyroid hormone levels were found to be the result and not the cause of RDS. T4 or T3 therapy is not warranted in this condition. PMID- 3096041 TI - Juvenile thyrotoxicosis. AB - The incidence of juvenile thyrotoxicosis has not exceeded one case per 100,000 population per year in Hungary during the past decades. From more than 200 simultaneous determinations of serum thyroid hormones (T3, T4, FT4) it was concluded that increased FT4 concentrations are the most frequent findings in thyrotoxicosis, even when both or one of the other thyroid hormone concentrations (T3, T4) are normal. TSH and prolactin responses to TRH were studied in 18 patients; TSH remained always undetectable whereas prolactin increased in half of the patients. A significant negative relationship was found between the prolactin response and the level of circulating thyroid hormone. Although the pituitary lactotrophin is controlled by thyroid hormones, thyrotrophin is more sensitive to thyroid hormone levels in juvenile thyrotoxicosis. In 56 TRH tests during antithyroid drug therapy this test was not found to be useful in predicting the likelihood of long-term remission. The low maintenance dose of antithyroid treatment (2.5-5.0 mg/day) without thyroid hormone addition seems to be a favourable mode of therapy in juvenile thyrotoxicosis. PMID- 3096042 TI - The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats. AB - Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal. PMID- 3096043 TI - Evidence against growth hormone-releasing factor deficiency in children with idiopathic obesity. AB - The mechanisms whereby growth hormone (GH) secretion is decreased in human obesity remain obscure. We studied the response of plasma GH and prolactin (PRL) to an I.V. dose of 0.5 mcg/kg of growth hormone releasing factor (GRF) in three groups of children: lean (N = 12), obese (N = 15) and GRF-deficient, i.e. children with complete GH deficiency on the basis of conventional provocative testing and evidence of hypothalamic dysfunction on the basis of thyrotropin releasing hormone testing (N = 7). Mean (+/- SEM) peak plasma GH after GRF was blunted to the same extent in obese and in GRF deficient children (11.1 +/- 2.2 and 8.3 +/- 2.8 ng/ml) as compared to lean control children (34.7 +/- 4.7 ng/ml). The pattern of PRL response to GRF was however different in GRF deficient children, whose high basal PRL levels increased further after GRF injection, and in obese and lean children, who had n alpha acute change in PRL levels after GRF. Baseline plasma somatomedin C concentrations were low for age in GRF deficient children and tended to be high for age in obese children. On the basis of these discrepant patterns of response of PRL to GRF and plasma somatomedin C concentrations, we conclude that GRF deficiency does not account for the decreased GH secretion observed in obese children. PMID- 3096044 TI - Circadian fluctuation of plasma melatonin in Prader-Willi's syndrome and obesity. AB - In 3 groups of 8 children and adolescents each with Prader-Willi-Labhart's Syndrome (PW-S), obese patients matched for body weight (control I), and normal weight subjects matched for pubertal stage (control II) plasma concentrations of melatonin, cortisol, growth hormone (hGH), insulin, gonadal hormones, and gonadotropins were measured every 1 to 4 hours in 24-hour-profiles. All hormones were determined by radioimmunoassay. The specific melatonin antibody was raised in rabbits. Criteria of the melatonin assay were as follows: detection limit for plasma concentrations of 13 pg/ml, intraassay and interassay variations: 8.4 and 11.2%, respectively. PW-S-patients showed cortisol fluctuations within normal limits. hGH was lower than 5 micrograms/l even during sleep, insulin ranged between 5 and 170 mU/l, and no excessively high glucose levels were found. Estradiol and testosterone were low for age and for pubertal development in all patients except in two girls. Basal LH and FSH levels were in the low normal range and showed sluggish response to LHRH. Plasma melatonin was low during the day, increased at mid-night and peaked at 3 a.m. Melatonin levels in PW-S were not significantly different from those in both control groups. We concluded that the impairment of gonadotropin secretion in patients with PW-S is not due to elevated levels of plasma melatonin. PMID- 3096045 TI - The role of regulatory peptides in postnatal metabolic adaptation. AB - Major changes occur after the umbilical cord is cut at birth in the structure and function of several physiological systems which enable the newborn baby to adapt from an intrauterine milieu of continuous intravenous nutrition via the placenta to a postnatal environment of intermittent enteral feeding with milk. The secretion of regulatory peptides from the gut and pancreas in response to enteral milk feeding may have a fundamental role in initiating and regulating the cascade of developmental changes needed for the utilization of food which occur after birth. PMID- 3096046 TI - Growth hormone response to thyrotropin-releasing hormone in children and adolescents: a reappraisal. AB - In normal subjects, thyrotropin-releasing hormone (TRH) is not involved in the control of growth hormone secretion. Paradoxical growth hormone (GH) responses to TRH have been described in acromegalic subjects and, recently, in some constitutionally tall children. To confirm this finding, we have examined the GH response to combined LHRH-TRH tests performed to assess the pituitary function of children with GH deficiency, tall stature before and during bromocriptine therapy, precocious or delayed puberty as well as in a group of patients of average height and normal bone age. Unlike prolactin, the GH "response" to TRH, in children followed longitudinally, is particularly heterogeneous with an unpredictable pattern of secretion in repeated tests. Over 90% of children display peaks of GH (greater than or equal to 5 ng/ml), of which 38% occur twice during the test period. Amplitude and frequency of GH peaks appear to be independent of height, chronological age or bromocriptine therapy. Secretory rate estimated by integrated surface area increases in parallel to sex steroids impregnation. The pattern of GH secretory episodes, the increase in mean GH secretion in parallel to the production of gonadal sex steroids and the failure of bromocriptine to affect GH secretion in constitutionally tall children allow to speculate that what is measured after TRH injection is normal spontaneous GH rhythm rather than a direct effect of TRH on GH secretion. PMID- 3096047 TI - Sex hormone priming prior to the combined hypoglycaemia test. AB - The insulin hypoglycaemia test (IHT) was performed on 3 groups of short stature children. One group was unprimed with sex steroid hormones, a second group received 17 beta-oestradiol, while a third group received testosterone. The dosage of insulin was adjusted to produce a nadir in blood glucose of reversible 1 mmol/L. When this level is achieved plasma growth hormone (GH) responses less than 10 mU/L are not improved by either priming procedure. It is suggested from the data that there is no place for a diagnosis of a partial GH deficiency state. When the IHT is combined with Gn-RH and TRH infusion the data derived may indicate GH-RH deficiency alone or additionally a CRF deficiency. Alternatively a pituitary insensitivity to these releasing substances or a pituitary synthetic failure of all trophic hormones may be adduced. Unless a releasing hormone is deficient and the pituitary is shown to be able to respond to its synthetic analogue, treatment with the available analogues will fail to give the desired clinical response. PMID- 3096048 TI - Low circulating somatomedin-C/insulin-like growth factor I in insulin-dependent diabetes and malnutrition: growth hormone receptor and post-receptor defects. PMID- 3096049 TI - Serum and urine monoclonal immunoglobulins in malignant non-Hodgkin's lymphoma. AB - 62 consecutive patients with newly diagnosed malignant non-Hodgkin's lymphoma (NHL) were investigated for the presence, type, and amount of serum and urine monoclonal immunoglobulin abnormalities. The overall incidence of monoclonal gammopathy (MG) was 81%. M components of the IgM and IgG classes were found in the serum of 52% of the patients. Their concentration was below 10 g/l in 54% of cases and above 20 g/l in 26% of cases. The highest incidence of serum M components (75%) was seen in plasmacytoid lymphocytic lymphoma (PLL) and the lowest (38%) in follicular center cell lymphoma. A monoclonal free light chain, i.e., Bence Jones protein (BJP), was documented in the urine of 61% of cases with a daily excretion comprised between 0.01 and 9.24 g. The isolated urinary excretion of BJP was a major finding accounting for 36% of all MG found in association with NHL. It occurred in all histopathological subtypes with a frequency ranging from 17% of PLL to 37% of small lymphocytic lymphoma. PMID- 3096050 TI - Bernard-Soulier syndrome: diagnosis by an ELISA method using monoclonal antibodies in 2 new unrelated patients. AB - Two unrelated patients with Bernard-Soulier syndrome and their relatives were studied. The patients demonstrated severe bleeding diathesis, the relatives were asymptomatic. The propositi showed the characteristic abnormalities of the syndrome: thrombocytopenia, a percentage of giant platelets higher than 65%, prolonged bleeding time and defective platelet aggregation to ristocetin and bovine plasma. On the contrary, in the heterozygotes, the typical abnormalities were not fully evident. We introduce a simple ELISA method for the precise definition of both homozygous and heterozygous states for the syndrome by the quantitation of platelet glycoprotein (GP) Ib. Specific binding of monoclonal antibodies anti-platelet GPIb was performed both by direct binding of radioiodinated antibody and by ELISA. Comparable results were obtained. In fact, we demonstrated near absence of GPIb in the 2 propositi and about half the amount in the heterozygotes studied compared to normal platelets. PMID- 3096051 TI - Plasma fibronectin in sickle cell disease. AB - Immunoturbidimetric assay technique was used to determine plasma fibronectin concentration in healthy Nigerian children (age 2-14 years), patients with sickle cell disease in steady state and patients with sickle cell disease in crises. Compared with controls, the plasma levels of fibronectin were greatly reduced in patients with sickle cell crises. Values within the normal reference range were seen in the group of patients with sickle cell disease in steady state. The data suggest that the significantly (p less than 0.001) reduced plasma fibronectin in patients with sickle cell crisis may be due to the consumption of this plasma protein in the process of erythrocyte endothelial adhesion. PMID- 3096052 TI - Redox and energetic state of red blood cells in G6PD deficiency, heterozygous beta-thalassemia and the combination of both. AB - The levels of ATP, ADP, AMP, NADP, NADPH, NAD, NADH and reduced glutathione were determined in the red blood cells of individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, beta-thalassemia (beta-thal) heterozygotes and in a boy carrying both mutations. The results obtained confirmed a reduced concentration of NADPH in G6PD deficiency and showed that with the combination of both diseases, the red blood cell contained practically undetectable levels of NADPH. Assays of some red blood cell enzyme activities known to be markedly influenced by cell age suggested that a younger mean red cell population is present in beta-thal/G6PD deficiency. Thus, the marked oxidative stress caused by beta-thal, that is apparently incompatible with G6PD deficiency, in fact exists, probably because of the residual activity of this enzyme in the younger red cells. PMID- 3096053 TI - Effects of transferrin genetic phenotypes on total iron-binding capacity. AB - Serum transferrin level and total iron-binding capacity (TIBC) were studied in a group of 297 healthy adult male subjects having HbAA and G6PDB+ phenotypes by standard chemical and immunoelectrophoretic techniques to examine the influence of different transferrin variants on these parameters. TIBC (67.1 +/- 13.4 mumol/l) and transferrin concentrations (27.0 +/- 3.95 mumol/l) for the whole group were found to be within reported normal values. Serum transferrin concentrations of the subjects having different electrophoretic variants and TfC subtypes of transferrin were not significantly different from each other. There was no significant difference of TIBC in relation to different electrophoretic variants of Tf. However, the TIBC of the subjects of the 1-1 subtype of TfC (70.4 +/- 13.6 mumol/l) was significantly higher than that of the 2-1 subtype (65.0 +/- 12.8 mumol/l; p less than 0.05) as well as that of the 2-2 subtype (60.4 +/- 11.4 mumol/l; p less than 0.01). PMID- 3096054 TI - Congenital dyserythropoietic anemia type I: report of a pair of siblings. AB - Two siblings affected with congenital dyserythropoietic anemia type I are described. They are the sixth familial occurrence reported. Particularly interesting is the comparison between the course and laboratory data of our cases. An unusual finding is the presence of the antigen 'i' on the erythrocytes of both patients. PMID- 3096055 TI - Double (IgA kappa + IgG kappa) paraproteinaemia in a single patient: immunofluorescence evidence for a common plasma cell clone 'frozen' at the switch phase. AB - We present a patient with multiple myeloma and double (IgA kappa + IgG kappa) paraproteinaemia in the serum. Immunofluorescence analysis of bone marrow plasma cell with fluorochrome-conjugated goat antibodies specific for mu, delta, gamma or alpha immunoglobulin heavy chain and kappa or lambda light chains revealed the presence of a plasma cell clone synthesizing simultaneously gamma, alpha and kappa chains. A minority of plasma cells synthesized gamma or alpha chains separately. Moreover, in the patient's peripheral blood, a few cells with the morphology of lymphoplasmoblasts and simultaneously positive for gamma, alpha and kappa chains were also detected. These results indicate that in this patient, the neoplastic plasma cell clone was 'frozen' at the differentiative step of the switch from IgG to IgA synthesis. PMID- 3096056 TI - Acute myeloid leukaemia developing in a patient with longstanding untreated chronic lymphocytic leukaemia. AB - A patient with chronic lymphocytic leukaemia untreated for 5 years subsequently developed acute myeloid leukaemia. It is suggested that reduced immunocompetence is the likely mechanism in this case and may also be a contributory factor in those cases which have been ascribed to the use of alkylating agents or radiation. PMID- 3096057 TI - Primary malignant lymphoma of the uterine cervix associated with cold-reacting autoantibody-mediated hemolytic anemia. AB - A 66-year-old woman presented with autoimmune hemolytic anemia of the cold antibody type as one of the first symptoms of a non-Hodgkin lymphoma (NHL) localized primarily in the uterine cervix. Cold-reacting autoantibody-mediated hemolytic anemia is a rare complication of NHL. Its occurrence as one of the presenting symptoms of NHL is even more unusual. The incidence of a primary malignant lymphoma in the genital tract is low. The combination of these phenomena in one patient make this case unique in the English literature. PMID- 3096058 TI - Analysis of antibody to neutrophils associated with autoimmune neutropenia: possible recognition of Fc-receptor-related molecules. AB - The serum of a 50-year-old male with neutropenia and a bout of bacterial infection was studied. Anti-neutrophil IgG antibody was detected by indirect immunofluorescence using a laser flow cytometry system. Purified IgG from our patient's serum did not inhibit chemotaxis of neutrophils, but inhibited rosette formation of neutrophils with ox red blood cells (ORBC) coated with anti-ORBC rabbit IgG dose-dependently. Surface iodination of neutrophils followed by their immunoprecipitation by purified IgG and sodium dodecylsulfate polyacrylamide gel electrophoresis showed a single band that corresponded to 45 kilodaltons. Possibly the IgG antibody in our patient's serum recognizes molecules related to Fc receptors. PMID- 3096059 TI - Autoimmune haemolytic anaemia associated with rheumatoid arthritis and paroxysmal nocturnal haemoglobinuria. PMID- 3096060 TI - Effects of lithium on the platelet count in neoplastic patients treated with polychemotherapy. PMID- 3096061 TI - [Effect of histones F1 and F2 alpha 1, chondroitin sulfate A and their complexes on platelet aggregation induced by ADP and arachidonic acid]. PMID- 3096062 TI - [Post-transfusion thrombocytopenic purpura associated with alloimmunization with Zw alpha (PlA1) platelet antigen]. PMID- 3096063 TI - Postoperative analgesia by nicomorphine intramuscularly versus high thoracic epidural administration. Effects on ventilatory and airway occlusion pressure responses to CO2. AB - In this study the effects of nicomorphine, administered either intramuscularly or by high thoracic epidural route, on the ventilatory and airway occlusion pressure response to CO2 were investigated and compared. Twenty-four patients scheduled for thoracic surgery were allocated randomly to postoperative pain relief by i.m. nicomorphine or by high thoracic epidural nicomorphine. The ventilatory response to 5% carbon dioxide was measured in all patients: first 1 day before operation, secondly on the first day after surgery immediately before nicomorphine administration and finally after the administration, at the moment when no further rise in end-tidal PCO2 (PETCO2) was measured. Respiratory response was assessed in two ways, by measuring minute ventilation (VE) and mouth occlusion pressure (P0.1). There was a significant depression in ventilatory response to CO2 in the intramuscular group (P = 0.03) due to nicomorphine as assessed by the slope of VE vs PETCO2. No significant depression was found in the epidural group, irrespective of measurement of VE or P0.1. No significant shift of apnoeic threshold-PETCO2 was observed in either group. PMID- 3096064 TI - Pulmonary ventilation, CO2 response and inspiratory drive in spontaneously breathing young infants during halothane anaesthesia. AB - Pulmonary ventilation, CO2 response and inspiratory drive were studied during halothane anaesthesia prior to surgery in 13 spontaneously breathing infants less than 6 months of age. Pneumotachography and capnography were used. Airway and oesophageal pressures were measured and occlusion tests were performed at functional residual capacity. Measurements were made before and during 8 min of 4% CO2 stimulation. Inspiratory drive increased significantly (P less than 0.001) at CO2 stimulation. This resulted in increased minute ventilation (P less than 0.001) and tidal volume (P less than 0.001) while respiratory rate was unchanged. As VBohrD/VT ratios were the same, the net effect was increased alveolar ventilation (P less than 0.001). CO2 elimination was unpredictable in these young infants and decreased during CO2 stimulation (P less than 0.05), while mean end tidal CO2 concentration only increased from 5.2 to 6.3% (P less than 0.001). The ventilatory response to 4% CO2 could therefore be deemed to be adequate during the short period (8 min) of CO2 breathing. However, this was achieved at the cost of increased work as witnessed by the increased ratio between minute ventilation and CO2 elimination (P less than 0.01). Stabilisation of end-tidal CO2 concentrations during CO2 inhalation took only 10 s while the maximal increase in ventilation volumes was not achieved until after 150 s. It is concluded that young spontaneously breathing infants anaesthetized with halothane (MAC 1.3) have an increased respiratory drive with greater tidal volumes during CO2 stimulations. Respiratory timing, dynamic compliance and total pulmonary resistance were, however, uninfluenced by 4% CO2 stimulation. Increased monitoring of CO2 output in anaesthetized infants is suggested. PMID- 3096065 TI - CO2 production and breathing pattern during invasive and non-invasive respiratory monitoring. AB - A computerized non-invasive strain gauge system for respiratory monitoring is described and compared with pneumotachography. With the use of simultaneous capnography, changes in breathing pattern, end-tidal PCO2 and CO2 production were evaluated during non-invasive (NIM) and invasive breathing monitoring (IM) in 14 healthy subjects. An overall absolute difference between measured and calculated tidal volumes of 4.6 +/- 3.47% (r = 0.97) was found. When switching from NIM to IM, tidal volume increased by 19% and breathing frequency decreased by 11% with a 10% increase in minute ventilation. These changes were mainly accomplished by an increased respiratory drive with the timing component unaltered. During IM both end-tidal PCO2 and CO2 production increased significantly as compared with those during NIM. PMID- 3096066 TI - The relationship between cerebral metabolic rate of oxygen and cerebral blood flow in the acute phase of head injury. AB - In 20 comatose patients (Glasgow coma scale less than or equal to 6 at admission) with severe head injury, the cerebral metabolic rate of oxygen (CMRO2) was calculated as the product of the hemispheric cerebral blood flow (CBF) and the arterio-venous oxygen content difference (AVDO2). The hemispheric CBF was calculated by the intracarotid 133xenon washout method by stochastic analysis as the average of 16 regions, and the measurements were performed within 3 weeks after the acute trauma. Generally no significant correlation (P less than 0.05) between CMRO2 and CBF was found, either in the total number of paired observations, in studies of hyperaemia defined as CBF greater than or equal to 30 ml 100 g-1 min-1; or in studies with reduced flow (CBF less than 30 ml 100 g-1 min-1). However, in about 50% of patients subjected to repeated studies within days, CBF was positively correlated to CMRO2, and this correlation was observed independently of the CBF value. Hyperaemia was associated with a significant decrease in AVDO2, a significant increase in both absolute and relative CO2 reactivity, and a significant increase in ventricular fluid pH; but not to an increase in intraventricular pressure, mean arterial blood pressure or significant changes in ventricular fluid lactate or lactate/pyruvate ratio. PMID- 3096067 TI - Anaesthetic problems in Hurler-Scheie syndrome. Report of two cases. AB - Hurler-Scheie syndrome is an intermediate form of mucopolysaccharidosis. Affected patients characteristically present in infancy with serious abnormalities including the upper airways and the lungs. We present two patients with Hurler Scheie syndrome and describe their anaesthetic management. One case was complicated by difficult endotracheal intubation and postoperative pneumonia. The second case was successfully managed using spinal anaesthesia and mild sedation. PMID- 3096068 TI - Computed tomography (CT) scan findings in children with seizures only. AB - One hundred and fifteen children with seizures only were studied with Computed Tomography (CT) scan at King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. Eighty percent of the children had normal CT scan; 8.7% showed cerebral atrophy and in only 11.3% was there a specific abnormality; such as infarction, porencephalic cysts, and arachnoid cysts. These specific type of abnormalities belong to partial and combined types of seizures and were treated medically. Fifty-seven cases of generalized type of seizures showed only 6 cases of abnormal CT scan and that is only brain atrophy. Based on these findings, we believe that CT scan should not be a part of the routine investigations of children with seizures only, especially those of generalized type. PMID- 3096069 TI - Memory disturbances in epileptic patients. PMID- 3096070 TI - Synergistic effects of oxiracetam and piracetam in combination with antiepileptic drugs. PMID- 3096071 TI - Calcium-induced damage of skeletal muscle fibers is markedly reduced by calcium channel blockers. AB - Vascular perfusion of rat hind limbs with a Ca2+-free physiological solution containing ethylenediaminetetraacetate, when followed by a physiological solution with normal concentration of Ca2+, caused a marked rise of creatine kinase (CK) in the venous effluent. When calcium channel blockers were present in the perfusing solutions, no rise of CK occurred. On histological sampling of perfused muscles, CK rise was roughly correlated with muscle fiber damage of the appropriate muscles. Removal of calcium from the plasmalemma of muscle fibers appears to prevent closure of calcium channels, making the muscle fibers susceptible to a deleterious influx of extracellular calcium. This influx can be prevented by the presence of calcium channel blockers in the perfusates. PMID- 3096072 TI - Sightsaving therapy in retinoblastoma. Experience with external megavoltage radiotherapy. AB - In Norway, sightsaving therapy in retinoblastoma has only been given to least affected eyes in bilaterally affected children. The results in 8 eyes given external high energy radiotherapy are reported. Additional focal therapy was given to 3 eyes for residual tumours and to one eye with new tumour at the ora serrata. Cataract was treated in 2 of the 3 eyes in which it developed. Vitrectomy was performed in 2 eyes with vitreous haemorrhage and persisting vitreous haze. Secondary enucleation has been avoided in all eyes 3-9 years after irradiation. One patient developed metastases in the temporal region at the enucleated side. Visual acuity is 6/12-6/6 if the macula has not been destroyed by tumour or focal therapy. Sightsaving therapy is presently also offered to unilateral cases and worst affected eyes in bilateral cases if the eyes belong to Reese-Ellsworth groups I-IV. PMID- 3096073 TI - Selenium supplementation during parenteral and enteral nutrition, short- and long term effects of two derivatives. PMID- 3096074 TI - Clinical improvement of congestive heart failure after selenium supplementation in total parenteral nutrition. PMID- 3096076 TI - Quantitation of noradrenaline nerve density in mouse iris by computer-assisted image analysis. AB - The density of noradrenaline (NA)-containing nerve fibres in mouse iris was measured with computer-assisted image analysis techniques both under normal conditions and during regeneration. Noradrenaline nerves were visualized by Falck Hillarp formaldehyde condensation technique in whole-mount spread preparations of mouse irides. The samples were analysed in a fluorescence microscope connected to a commercially available image analysis system (IBAS/Kontron). A software program was developed for specific detection of fluorescence and the nerve density was determined by calculating the area covered by fluorescence in percentage of total measuring field. The method showed good reproducibility as observed both when repeated measurements were performed in the same measuring field or when consecutive measurements on the same set of irides were performed. Also the inter assay variation between control values in the different experiments was low. Loading of the adrenergic nerves by incubation in alpha-methyl-NA or conditions leading to partial diffusion of the fluorophore had minor effects on the nerve density values. The regeneration of the NA nerve fibres after a selective toxic sympathectomy with 6-hydroxydopamine was also studied. The nerve fibre density values measured by image analysis correlated well with the uptake of [3H]NA; the endogenous NA levels recovered much more slowly, however. It thus seems that endogenous transmitter levels might be a somewhat insensitive index of nerve terminal regrowth, at least in early stages of regeneration. The results indicate that image analysis is a powerful tool to quantitate a transmitter-identified nerve terminal network in a histological preparation. PMID- 3096075 TI - Axonal transport of synapsin I- and cholinergic synaptic vesicle-like material; further immunohistochemical evidence for transport of axonal cholinergic transmitter vesicles in motor neurons. AB - The axonal transport of organelles in motor axons in the sympathectomized rat sciatic has been studied using two antisera which recognize specific components of synaptic vesicles. Anti-synapsin I recognizes synapsin I (SYN I) which is affiliated with the external membrane of synaptic vesicles, while rabbit-anti synaptic vesicle antiserum (RASVA) recognizes integral membrane glycoproteins in cholinergic synaptic vesicles. Immunofluorescence studies, including cytofluorimetric scanning, show that immunoreactive (IR) material recognized by both antisera: rapidly accumulate proximal to a crush; the material has a granular appearance in the microscope; is redistributed in an isolated segment, and that the transport of the material is sensitive to vinblastine. Thus the proximodistal transport has the characteristics of fast axonal transport. Furthermore, recycling organelles, accumulating on the distal side of a crush are recognized by RASVA, but carry only very little SYN I-IR. The results give further support to the hypothesis that motor cholinergic axons transport axonal cholinergic vesicles towards the motor endplates. PMID- 3096077 TI - The effect of inhaled carbon dioxide and hypoxia mixtures on the electrical and mechanical activities of respiratory muscles in dogs. AB - The effects of hypercapnia and hypoxia on the regulation of breathing was studied in six mongrel dogs during pentobarbital anaesthesia with special reference to their action on the respiratory muscles. Carbon dioxide (5.5% in air) inhalation produced an increase of minute volume due to augmentation of respiratory frequency and tidal volume. The number of electrical impulses per breath remained unaffected despite the increase tidal volume. Therefore the mechanical ventilation increased more than the electrical output to the respiratory muscles indicating that the efficiency of the muscles increased. The tidal volume increased more than the pressure impulse (mechanical work by the respiratory muscles) suggesting that the airway conductance was increased during hypercapnia. During hypoxic stimulus (11% oxygen in nitrogen) the increase of minute volume was due to increase in respiratory frequency. The ratio of tidal volume to the number of electrical impulses in the respiratory muscles remained unaltered. During combined carbon dioxide and hypoxia stimulus the responses were similar to those of carbon dioxide stimulus alone. However, the increase of minute volume and the increase in the ratio of tidal volume and pressure impulse to the number of electrical impulses in the respiratory muscles were more pronounced. These findings suggest that carbon dioxide affects the regulation of breathing above the respiratory muscles and in the muscles themselves. Hypoxic stimulus seems not to have any direct effect on the respiratory muscles in dogs during pentobarbital anaesthesia. PMID- 3096078 TI - Effects of TRH on cerebral and peripheral blood flows; role of submesencephalic brain stem centres. AB - The localization of the origin of the cardiovascular effects elicited by thyrotropin-releasing hormone (TRH) was attempted in this study. The radioactively labelled microsphere method was employed for measurement of regional cerebral (rCBF) and peripheral blood flow in albino rabbits anaesthetized with urethane. The effect of 50 micrograms and 2 mg kg-1 TRH (administered i.v.) on rCBF and peripheral blood flow was evaluated in animals with the brain stem sectioned (BSS) at the level of pons-mesencephalon. The cerebral vasodilating effect of TRH was abolished or attenuated, while the peripheral vasoconstriction and increase in mean arterial blood pressure (MAP) was unaffected. Cordotomy at the CI level caused a marked fall in MAP and abolished the pressor response to TRH. In animals infused with angiotensin II, in order to normalize the decreased MAP after cordotomy, TRH caused a marked increase in rCBF. Administration of 50 ng and 5 micrograms TRH into the fourth ventricle caused a marked peripheral vasoconstriction and pressor response. The same amounts of TRH administered into the mesencephalic aqueduct caused a marked increase in rCBF and peripheral vasoconstriction. The results indicate that TRH elicits the pressor and peripheral vasoconstrictor responses from a submesencephalic brain stem region. The increase in rCBF caused by TRH is probably mediated by a somewhat higher submesencephalic level. PMID- 3096079 TI - Concentration dependence of halide fluxes and selectivity of the anion pathway in toad skin. AB - The isolated toad (Bufo bufo) skin was mounted under voltage-clamp conditions in a chamber shown to cause no significant edge damage. The serosal side of the skin was bathed with NaCl-Ringer's, and the passive voltage-sensitive anion conductance studied in its fully voltage activated state, V = -80 mV (apical bath negative). The active sodium currents were eliminated by replacing external Na+ with K+. With [Cl-]o varying between 1.45 mM and 110 mM (gluconate substitution) and [I-]o = 3 mM, the total clamping current (y) and the sum of halide currents (x), estimated from flux measurements, were related by y = 1.0x-3.7 microA cm-2 (r2 = 0.98, n = 50 preparations). The increase in [Cl-]o produced a sigmoidal increase in Cl- influx and clamping current, with the rate coefficient for the influx increasing with [Cl-]o for 1.45 less than [Cl-]o less than 60 mM, but decreasing slightly again as [Cl-]o was further raised to 110 mM. A similar relationship was obtained between the rate coefficient for the Br- influx and [Br ]o, and the I- influx and [Cl-]o, indicating that these three ions are transported by a pathway that is activated by Cl-o and Br-o. The rate coefficients for the influxes ranked as follows, I-:Cl-:Br- = 0.7:1:1.3. The I /Cl- selectivity was shown to be independent of the degree of Cl-o activation of the anion pathway, and identical with the I-/Cl- selectivity of a furosemide sensitive, conductive pathway. With [Cl-]o, [Br-]o, or [I-]o = 110 mM, the currents ranked as follows, Cl-:Br-:I- = 1:0.68:0.06, indicating that Cl-, to a lesser extent Br-, and I-, poorly activate the conductive anion pathway. External I- was a potent inhibitor of the Cl-o activation of the Cl- conductance. The unidirectional I- fluxes ([I-]o = [I-]i = 3 mM, [Cl-]o = [Cl-]i = 110 mM) revealed passive transport for V less than -50 mV, active transport for V = o mV, and exchange diffusion for V = 50 mV, confirming our previous finding that depending on the transepithelial potential, the toad skin exhibits three modes of anion transport. A model that shares some properties with that of the anion transport system of the red cell membrane accounts for our findings, and for an inwardly directed active Cl- flux in terms of Cl-/HCO3- exchange. PMID- 3096080 TI - [Studies of pyrazine derivatives. XVII. Synthesis and the tuberculostatic activity of pyrazinyl-1,3,4-oxadiazole derivatives]. PMID- 3096081 TI - Positron emission tomography of cavernous haemangiomas of the brain. AB - Four cases with lesions suspected to be low-grade intracerebral tumours but later proved to be cavernous haemangiomas are described. The patients were examined with contrast enhanced CT and with positron emission tomography (PET). The lesions were partly calcified with a mild or no mass effect and a slight contrast enhancement at CT. There were signs of disrupture of the blood-lesion barrier also on radionuclide studies. PET with 11C-methionine and 11C-glucose showed a normal or decreased accumulation of the tracers. This combination of findings has not been encountered in intracranial tumours. As a comparison, one case of glioblastoma is described. In this patient, the CT findings suggested a cavernous haemangioma. However, PET showed a markedly increased accumulation of 11C methionine, which is compatible with brain tumour but not with haemangioma. PMID- 3096082 TI - The jugular bulb diverticulum. A radioanatomic investigation. AB - Two hundred and forty-five temporal bone specimens were examined radiographically. Subsequently the topographic relationship between the jugular fossa and surrounding structures was evaluated in plastic casts of the specimens. Fifty-eight casts showed a high jugular fossa and in 17 a jugular bulb diverticulum was found. A diverticulum is regarded as an anomaly of the high jugular bulb and presumably has a potential for expansion. Most frequently a diverticulum was directed medially into the space between the internal acoustic meatus, the vestibular aqueduct and the posterior cranial fossa. Seven diverticula reached the level of the internal acoustic meatus. Encroachment upon the vestibular aqueduct was seen in 4 casts and both the internal acoustic meatus and the cochlear aqueduct were very close to the diverticulum. A few diverticula were directed postero-laterally close to the facial canal and the stapedius muscle. The investigation was supplemented with a selected clinical material of radiographs of temporal bones with high fossae. The results corresponded to those of the experimental investigation. The jugular bulb diverticulum is a relatively common feature and should be regarded as an anomaly with a potential to give rise to clinical symptoms consequent to its intrusion upon surrounding structures. PMID- 3096083 TI - Duodenal diverticula demonstrated by barium examination. AB - An investigation for biliary tract calculi and food-stimulated gastro-oesophageal reflux was carried out in 37 patients with duodenal diverticula demonstrated by barium examination. Sixty per cent of the diverticula were located in the descending part of the duodenum. Biliary tract calculi were demonstrated in 38 per cent and food-stimulated gastro-oesophageal reflux in 81 per cent of the patients. The detection of a duodenal diverticulum should result in a supplementary investigation for gallstones and gastro-oesophageal reflux and its sequelae. PMID- 3096084 TI - [Mathematical modeling and simulation of the process of single-stage continuous cultivation in the production of L-lysine]. PMID- 3096085 TI - [Partial "primary" epilepsies. Case series of the Center for the Study of Epilepsy of the Neurology Clinic of the 2d Faculty of Medicine of Naples]. PMID- 3096086 TI - [Treatment of tic hyperkinesias with sodium valproate during their evolutionary stage. Preliminary findings]. PMID- 3096087 TI - [Deprenyl as a co-adjuvant in the treatment of Parkinson disease]. PMID- 3096088 TI - Serum concentrations of diazepam and its metabolite desmethyldiazepam in epileptic patients after chronic diazepam treatment. PMID- 3096089 TI - Activation of cellular oncogenes in hemopoietic cells by chromosome translocation. PMID- 3096090 TI - Effect of subdermal levonorgestrel contraceptive implants on vaginal candidiasis. AB - A total of 150 women in 3 equal groups, each using a different contraceptive method (group I used Norplant, group II used the IUD and group III used combined OC pills) were investigated for the presence of vaginal candidiasis before and at various time intervals (3, 6 and 12 months) after starting to use the particular contraceptive method. The incidence of vaginal Candida albicans infection increased significantly among pill and IUD users, but with a much lower intensity among the latter cases. In Norplant users the increase was slight and insignificant. The explanation of these findings within the context of changes in local vaginal milieu is discussed. PMID- 3096092 TI - Treatment of motility abnormalities of the esophagus. PMID- 3096091 TI - Persistent cervicovaginal actinomyces-like organisms following antibiotic therapy in an IUD user. PMID- 3096093 TI - Total parenteral nutrition in the cancer patient. AB - Malnutrition is a common accompaniment of malignant disease and clearly places the cancer patient at increased risk. Adequate nutritional rehabilitation of the malnourished cancer patient can correct abnormal nutritional indices. In the surgical patient, this has been shown to decrease perioperative morbidity and mortality. Nutritionally repleted patients undergoing radiation or chemotherapy may be more tolerant and, therefore, more likely to respond to treatment although, thus far, a favorable effect on outcome has not been demonstrated conclusively. Patients who are to receive multimodal treatment with chemotherapy, radiotherapy, and surgery are at a particularly high risk for the development of malnutrition, and the institution of one treatment may be predicated on recovery from the previous therapy. When a major abdominal surgical procedure is part of the treatment plan, TPN may be required to prevent malnutrition in an otherwise nutritionally intact patient at the outset of therapy. For patients in whom TPN is indicated, adequate nutritional restoration is of paramount importance. Calories and nitrogen in excess of amounts predicted for noncancer patients may be required. Sequential nutritional assessment is a must to assure the adequacy of nutritional repletion. Considerations of cost and simplicity make the enteral route the preferred avenue for nutritional repletion if the gut is available for use. Certainly, when indicated, however, the risk and expense of parenteral nutrition is justified, particularly in the surgical patient. At present there are no data to justify the use of one particular amino acid formulation or energy source over another. A balanced amino acid solution with glucose as the primary energy source seems equally as efficacious as specialized amino acid formulas and lipid as the primary calorie source. PMID- 3096094 TI - [Urogenital bilharziasis. 3 recent case reports. Diagnostic elements. Medical treatment]. PMID- 3096095 TI - [A case of heterotopic bone formation in the kidney]. AB - A case of heterotopic bone formation in the right kidney is presented. The case was a 58-year-old woman who complained of right flank pain. Excretory pyelography revealed that the kidney was nonfunctioning and had a few calcification shadows. The right kidney was removed. By histological examination of the surgical specimen, the heterotopic bone formation with bone marrow was found beneath the renal pelvic mucous membrane. PMID- 3096096 TI - Esophageal intramural pseudodiverticulosis: a reevaluation. AB - Esophageal intramural pseudodiverticulosis is an unusual condition manifested by tiny flask-shaped outpouchings in the wall of the esophagus. The condition was diagnosed in 21 (0.15%) of 14,350 patients undergoing radiologic examinations of the esophagus at our hospitals. The pseudodiverticula were detected only by single-contrast technique in five of 18 patients (28%) who underwent both single- and double-contrast examinations. Thus, thin, low-density barium seems to enter these structures more readily than the high-density barium used for double contrast esophagography. While most patients reported in the literature have diffuse or segmental pseudodiverticulosis associated with high esophageal strictures, the majority of our patients (11 [52%] of 21) had isolated involvement of the distal esophagus with 10 or fewer pseudodiverticula in the region of a peptic stricture. Other associated conditions included Candida esophagitis, herpes esophagitis, and squamous cell carcinoma of the esophagus. Our experience suggests that pseudodiverticulosis usually represents a sequela of reflux esophagitis, although the reason that so few patients with esophagitis develop this condition is unclear. PMID- 3096097 TI - MR of hemorrhage: a new approach. AB - Using a modification of the partial saturation (PS) pulse sequence, we developed an MR method that permits the acquisition of highly T1- and T2-weighted images of the head and body in as little as 10 sec. The PS images, which were acquired at 0.6 T in a series of six patients with acute and subacute hemorrhage, showed a striking reduction in the signal intensity of hemorrhagic lesions. This effect, which is related to bulk magnetic susceptibility variations, was either minimal or absent on conventional T1- and T2-weighted spin-echo (SE) images. Our results suggest that high-field systems are not needed in order to image acute and subacute hemorrhage. PMID- 3096098 TI - MR of the diaphragma sellae. AB - The appearance of the diaphragma sellae is described in cryomicrotomic sections and on MR in patients with and without intra- and suprasellar masses. On MR, it appears as a thin band of negligible signal that is best shown when adjacent CSF or a mass has greater signal intensity. Its position or absence can be used to differentiate intrasellar masses with suprasellar components from suprasellar masses. PMID- 3096099 TI - Significance of cerebellar tonsillar position on MR. AB - It has been noted that a low degree of ectopia of the cerebellar tonsils on MR is of questionable significance. We measured the position of the cerebellar tonsils with respect to the inferior aspect of the foramen magnum in 200 normal patients and in 25 patients with a firm diagnosis of Chiari I malformation. In the normal group, the mean position of the tonsils was 1 mm above the foramen magnum with a range from 8 mm above the foramen magnum to 5 mm below. In the patients with Chiari I malformations, the mean position was 13 mm below the foramen magnum with a range from 3 mm below the foramen magnum to 29 mm below. Fourteen percent of normal patients had tonsils extending slightly below the foramen magnum. If 2 mm below the foramen magnum is taken as the lowest extent for tonsils in a normal patient, our sensitivity in predicting symptomatic patients is 100% and our specificity is 98.5% (three false positives). If 3 mm below the foramen magnum is taken as the lowest normal tonsillar position, our sensitivity is 96% and our specificity is 99.5%. MR demonstration of less than 2 mm of tonsillar ectopia is probably of no clinical significance in the absence of syringomyelia. PMID- 3096100 TI - The detection of intracranial calcifications by MR. AB - Twenty patients in whom CT had unequivocally demonstrated the presence of calcification in a diversity of lesions and who had undergone MR, performed at 0.6 T and with standard T1- and T2-weighted pulse sequences, were retrospectively studied to determine the MR signal-intensity characteristics of the calcifications and to assess the ability of MR to detect the presence of this abnormality. CT proved superior to MR in detecting and characterizing calcification. In seven of 20 cases, the apparent extent of calcification was equal by both imaging techniques, and in 13 of the 20 cases, CT showed more extensive abnormality. In five of the 20 cases, the calcifications were seen by MR as regions of profoundly reduced signal intensity, approximately equal to cortical bone, in all pulse sequences. In 12 of the 20 cases, the signal intensity was profoundly reduced in one or more, but not all, pulse sequences. T2 weighted pulse sequences were most sensitive in detecting calcification of signal void. Reviewed without knowledge of the CT findings, the MR images were interpreted as definitely indicative of the presence of calcification in three of the 20 cases. In seven of the 20 cases, the MR images raised the possibility of calcification but were less definitive than the CT findings. In 10 of the 20 cases, MR was judged indeterminate for the presence of calcification. PMID- 3096101 TI - High-flow angiopathy: cerebral blood vessel changes in experimental chronic arteriovenous fistula. AB - Profound vascular damage secondary to high-flow extracranial states has been well characterized. However, changes in cerebral vasculature secondary to high-flow states have not been studied. To determine changes related to high-flow states in cerebral vessels, a rabbit model was developed in which torrential flow was created in the vertebrals, carotids, basilar, and vessels of the circle of Willis by means of a carotid-jugular shunt after ligation of the proximal carotid. The clinical, angiographic, and histologic changes noted in the animal model include: abrupt clinical deterioration after a variable interval with some animals developing ptosis, afferent vessel dilatation and the development of prominent anastomotic channels, variable cerebral vessel histopathology--related to duration and relative proximity to the shunt--affecting all three vessel layers, plump, irregular, and clumped endothelium, denuded with adherent platelets, irregular, duplicated, and thinned internal elastic membrane, frayed with invasion of the intima by mesenchymal cells, vacuolization and necrosis of the media muscle, and invasion of adventitia by foreign cells and small blood vessels. The high-flow angiopathy seen in this model may help explain vascular changes associated with high-flow cerebral vascular lesions, as well as other types of vascular damage. PMID- 3096102 TI - CT in iatrogenic cerebral air embolism. AB - Three patients with suspected iatrogenic cerebral air embolism had cranial CTs performed within 24 hr of onset of symptoms. One was interpreted as normal, one showed a large, right frontoparietal enhancing lesion, and the third showed evidence of bi-thalamic infarction. Follow-up scans 7 to 10 days later showed either single or multiple enhancing infarcts in all patients. Although CT proved a valuable tool in the diagnosis of this condition, one out of three initial studies were negative, necessitating a follow-up scan. PMID- 3096103 TI - Gas bubbles in polymethylmethacrylate cranioplasty simulating abscesses: CT appearance. AB - Polymethylmethacrylate (PMMA) cranioplasty procedures were performed on 20 patients over a 2-year period. Nine of these patients had a total of 17 CT examinations, performed when clinically indicated. On 16 of the 17 CT scans, the appearance of the cranioplasty plate was characteristic of plates with gas bubbles. The appearance of these bubbles was stable over an extended period of time, ruling out clinical reasons for this appearance. The original interpretations of the CT scans were variable, inconclusive, or even erroneous. An understanding of the application of PMMA plates and their characteristics is necessary to accurately interpret the CT appearance of the PMMA cranioplasty plate. PMID- 3096104 TI - Incidental paranasal sinus abnormalities on CT of children: clinical correlation. AB - The paranasal sinuses were prospectively evaluated by CT, clinical history, and physical examination in infants and children having cranial CT for indications unrelated to upper respiratory inflammation (URI). One hundred and one CT scans were studied, and sinus abnormalities were detected in 18% of patients older than 1 year and without signs or symptoms of URI. When signs and/or symptoms of recent URI were present, the incidence of abnormalities was 31%. Maxillary antral were not identifiable or were opacified in 72% of all infants under 1 year old. Because of the high incidence of sinus abnormalities on CT in children with and without evidence of recent URI, abnormalities should not be ascribed to sinusitis without close clinical correlation. PMID- 3096105 TI - Pneumosinus dilatans of the sphenoid sinus. AB - Four cases of pneumosinus dilatans of the sphenoid sinus are reported, supplementing the eight cases previously reported in the literature. This rare entity is characterized by expansion of a paranasal sinus that contains only air. In one patient, severe visual loss due to compression of the optic canal by the adjacent enlarged sinus was seen. Galactorrhea occurred in one patient, and three of the four patients reported headaches. There was dehiscence of the sinus roof in two cases, which apparently resulted in a cerebrospinal fluid fistula in one. Previous reports of this entity are reviewed, and the radiographic findings and clinical presentations are discussed. It is proposed that the term "pneumosinus dilatans" be used to describe all dilated, air-filled sinuses with outwardly bulging walls when the primary cause is uncertain. PMID- 3096106 TI - Sideways dislocation of the temporomandibular joint meniscus: the edge sign. AB - Seventy temporomandibular joint arthrograms of 49 patients with symptoms of internal joint derangement were reviewed. Twenty-three of these arthrograms (33%) were abnormal but atypical for anteriorly dislocated meniscus. The lower temporomandibular joint space had a well-defined edge located inferiorly, which was attributed to pressure from a sideways-dislocated meniscus. We called this appearance the "edge sign." Seven patients with radiologically apparent sideways dislocation were operated on. The meniscus was dislocated laterally in six and medially in one. The incidence of irreducibility and perforation was higher in sideways-dislocated than in anteriorly dislocated menisci. PMID- 3096107 TI - Cranial sonography of the occipital horns and gyral patterns in the occipital lobes. AB - Cranial sonographic examinations of 199 neonates were evaluated to determine the incidence of an echogenic pattern in the occipital lobe that simulated a mass, to relate that finding to the birth weight, and to correlate it with the gyral development of the occipital lobe. This echogenic pattern was seen in infants weighing less than 1750 g at birth and was identified on both sides of the midline on the most medial paramedian sagittal sonogram scans of the head. This pseudomass was found to be due to close approximation of a large occipital horn and calcarine fissure joining other adjacent secondary fissures. The multiple fissures formed an echogenic star, and the proximity of the occipital horn and premature brain tissue texture contributed to the relatively hypoechoic background of the pseudomass. The pseudomass is limited superiorly by the parietooccipital fissure and inferiorly by the tentorium. This sonographic pattern should be recognized as a normal variant. PMID- 3096108 TI - The MR appearance of CSF pulsations in the spinal canal. AB - We investigated the MR appearance and incidence of low-signal areas within the CSF of the spinal canal. Nonuniform areas of decreased signal intensity in intracranial CSF have been named the CSF flow-void sign (CFVS) and appear to be due to spin dephasing secondary to pulsatile CSF motion. Similar areas are seen in the spinal canal. The MR scans of 50 randomly selected patients, constituting a total of 63 spinal studies, were reviewed. There were 27 cervical, 16 thoracic, and 20 lumbar spine examinations. All patients were studied using T2-weighted and T1-weighted spin-echo pulse sequences. T2-weighted images were done with sufficiently long TE and TR to cause the CSF to appear hyperintense compared with brain and spinal cord tissue. Two patients with enlarged spinal canals and two patients with syringohydromyelia were also included to illustrate the appearance of prominent CSF pulsations. The CFVS was identified on T2-weighted scans in the cervical spinal canal in nine patients (33%), in the thoracic spinal canal in one patient (6%), and possibly in the lumbar spinal canal in two patients (10%). The CFVS was prominent in two patients with enlarged CSF spaces and was also seen in the intramedullary cavity of the patients with syringohydromyelia. The CFVS could obscure small dural lesions and, in some instances, simulate enlarged vessels. Recognition of the spinal CFVS is important to avoid the incorrect diagnosis of intraspinal lesions. PMID- 3096109 TI - Surface coil MR of spinal trauma: preliminary experience. AB - Nineteen fractured vertebral bodies involving the spine from C1 to L2 in 14 patients were imaged with a 0.6-T magnet using prototypical surface coils. Ten of these patients were studied within the first week of trauma. CT and plain films are superior to MR in detecting fractures and identifying the origin of displaced fragments in cases of extensive comminution. However, all body fractures and most posterior element fractures in the thoracolumbar spine were visible on MR. Fractures involving the cervical neural arch were difficult to detect on transverse section without CT correlation. Our results indicate that MR can probably replace CT in the thoracolumbar region. MR is superior to CT in demonstrating ligamentous injury and trauma to the disk. Unlike CT, MR shows the relation of the thecal sac and spinal cord to retropulsed fragments and epidural hematoma. MR also visualizes cord parenchyma; two cases of cord hemorrhage were not seen on CT. Even at this early stage of development, surface coil MR promises to become important in the evaluation of spinal trauma, not only in assessing the integrity of the spinal canal and cord, but in separating stable from unstable fractures on the basis of disruption of the posterior ligaments and elements. Additionally, the demonstration of rupture of specific ligaments may have an impact on surgical management. PMID- 3096110 TI - Pharmacokinetics of lopamidol after intrathecal administration in humans. AB - The kinetics of iopamidol, a new nonionic radiocontrast agent, were evaluated in 10 patients undergoing lumbar myelography. The doses of iopamidol administered intrathecally were 11 and 15 ml of a 200-mg iodine per ml solution in one and nine patients, respectively. Radiographs were made within 30 to 40 min and CTs were taken at about 1, 6, and 23 hr after iopamidol administration. The diagnostic quality and usefulness of the conventional and CT myelograms were considered excellent. In the lumbosacral subarachnoid space, the densitometry CT readings were maximal at 1 hr, whereas in the cervical subarachnoid space, peak CT values were reached at 6 hr. Plasma and urine samples were taken at frequent intervals up to 48 hr after the contrast agent was administered. Peak plasma levels of iopamidol were observed at 2.9 hr and were no longer detectable at 48 hr. The 48-hr urinary recovery for all patients averaged 66 +/- 8% of the dose. In all but one patient, iopamidol was cleared almost completely from the CSF within 24 hr. Side effects after iopamidol administration were transient and minor, and were not related to the CT readings or its systemic clearance. PMID- 3096111 TI - The push-up view: a superior cross-table lateral projection for cervical myelography. PMID- 3096112 TI - Traumatic atlantooccipital dislocation: two cases with survival. AB - These two cases with long-term survival after anterior and posterior AO dislocation point out the importance of making the diagnosis. Our simple technique of rapid CT confirmation of AO dislocation is a practical adjuvant procedure, particularly in patients with suspected intracranial injury. PMID- 3096113 TI - Intradural spinal teratoma: case report and review of the literature. PMID- 3096114 TI - Cystic meningioma presenting as a ring lesion. PMID- 3096115 TI - Horner's syndrome secondary to traumatic pseudoaneurysms. PMID- 3096116 TI - Intravascular balloon embolization of a carotid-ophthalmic artery aneurysm with preservation of the parent vessel. PMID- 3096117 TI - Angiographic follow-up of large cerebral AVMs incompletely embolized with isobutyl-2-cyanoacrylate. AB - This study evaluated the long-term angiographic results in large cerebral arteriovenous malformations (AVMs) partially embolized with isobutyl-2 cyanoacrylate. Preembolization, immediate postembolization, and long-term follow up angiograms were performed in 30 large, partially embolized brain AVMs. Particular attention was paid to the relative size of the residual AVM nidus and the embolized arterial feeders, to recruitment of new feeders, to the size of residual draining veins, and to the speed of arteriovenous shunt. Nine cases with less than 50% AVM nidus obliteration showed no significant morphologic changes. In 18 cases with 50-75% obliteration of the AVM nidus, 11 (61.1%) showed no significant changes, six (33.3%) showed enlargement of the AVM nidus, and one (5.5%) evolved to complete angiographic obliteration. In three cases with 75-99% AVM nidus obliteration, one remained unchanged, one showed an increase in the size of the AVM nidus, and one evolved to complete obliteration. Evaluation by plain film, CT, and cerebral angiography of the isobutyl-2-cyanoacrylate deposits showed that when the polymer was positioned predominantly in arterial feeders there was invariably reconstitution of the AVM nidus through leptomeningeal, deep medullary, and/or dural collaterals. This phenomenon did not occur when the isobutyl-2-cyanoacrylate was deposited mainly in the AVM nidus. PMID- 3096118 TI - Functional angiography of the head and neck. AB - The basic concepts of the territorial approach to angiography and intravascular embolization of vascular lesions of the head and neck are reviewed. Superselective arteriographic injections are performed in sequences and projections tailored to the suspected location of the vascular lesion. The resulting studies are then reviewed as a whole, so that a complete angiographic map of the tissue territory involved is considered. From this map the interventionalist selects the best and safest route for embolization, taking into account developmental and acquired constraints to blood flow and the presence of any potentially dangerous collateral flow toward normal nervous tissue. Case studies are presented to illustrate the most frequently encountered anatomic variants that may, by their presence within the circulation to be embolized, increase the risk of complication. Attention is directed toward the probability of intraprocedural changes in hemodynamic balance and flow direction, which also may increase risk and which may be modified by catheter techniques and minimized by meticulous attention to detail. This article should support the contention that functional angiography and careful attention to the resulting angiographic map are essential for efficacious and safe head and neck embolization. PMID- 3096119 TI - Percutaneous embolization of arteriovenous fistulas of the external carotid artery. AB - Nineteen arteriovenous fistulas of the external carotid branches in 17 patients were treated by a variety of percutaneous transvascular techniques. There were nine females and eight males; 11 fistulas were traumatic in origin, five were "spontaneous," and three were thought to be congenital. The most frequent presenting symptoms were a bruit and thrill, followed by pulsatile tinnitus, pulsatile mass, headaches, and ocular problems. The symptoms were related to fistula site and venous drainage. The middle meningeal artery was involved most often, followed by the superficial temporal, occipital, internal maxillary, and ascending pharyngeal arteries. All patients except one were successfully cured, including one recurrence. There were no complications, and the hospital stay averaged 3 days. PMID- 3096120 TI - Preoperative embolization of the head and neck: indications, patient selection, goals, and precautions. AB - Preoperative embolization was performed in 39 patients with 44 paragangliomas of the head and neck. Because of their complex vascular supply and their relation to vital structures such as the internal carotid artery and the lower cranial nerves, paragangliomas of the temporal bone represent challenging lesions to both the neuroradiologist and the otoneurosurgeon. Detailed classification by high resolution CT and recognition of the multi- or monocompartmental vascular composition and of dangerous situations by selective angiography are essential prerequisites for safe and effective devascularization of paragangliomas of the temporal bone. Major complications that may occur if embolic material reaches intraaxial vessels through anastomoses between external carotid artery branches and the internal carotid and/or the vertebral artery can be avoided with the use of specific precautionary techniques. Palsies of the facial and lower cranial nerves can also be avoided if reabsorbable material is used for embolization of vessels supplying cranial nerves in asymptomatic patients. In selected cases with significant supply from the internal carotid artery, special interventional techniques, including embolization of the pericarotid tumor portion through the caroticotympanic artery and pre- or peroperative balloon occlusion of the petrous internal carotid artery, allow radical removal of extensive paragangliomas of the temporal bone. Techniques and selection of materials for embolization of carotid body, vagal body, and other paragangliomas of the head and neck mainly depend on the vascular composition of the tumor and on the specific vascular territory in which the tumor is located. In this series, preoperative embolization significantly improved surgical conditions of paragangliomas of any location in the head and neck and proved to represent an essential prerequisite for successful surgery of extensive paragangliomas of the temporal bone. PMID- 3096121 TI - Preoperative embolization of intracranial meningiomas. AB - The goal of preoperative embolization of intracranial meningiomas is to facilitate their surgical removal by reducing tumor vascularity and decreasing blood loss during surgery. This study is based on personal experience with about 100 embolized meningiomas and on the experience of others. Embolization is performed during the same session as diagnostic angiography. The appropriate embolic materials (absorbable or nonabsorbable) are chosen according to the location of the tumor, the size of the feeding arteries, the blood flow, and the presence of any potentially dangerous vessels (dangerous anastomoses between external carotid artery and internal carotid or vertebral arteries, arteries supplying the cranial nerves). Preoperative embolization appeared to be very useful in large tumors with pure or predominant external carotid artery supply (convexity meningiomas), in skull-base meningiomas, and in middle fossa and paracavernous meningiomas. It was also useful in falx and parasagittal meningiomas receiving blood supply from the opposite side and in posterior fossa meningiomas. CT low densities demonstrated after embolization did not always correlate with necrosis on microscopic examination, and large areas of infarction could be found despite normal CT. Embolic material was found on pathologic examination in 10%-30% of cases; fresh or recent ischemic and/or hemorrhagic necrosis consistent with technically successful embolization was demonstrated in 40%-60% of cases. With careful technique complications are rare. PMID- 3096123 TI - Left-right temporal region asymmetry in infants and children. PMID- 3096122 TI - Acute traumatic vacuum sign. PMID- 3096124 TI - Giant internal carotid artery aneurysm masquerading as a paranasal sinus tumor. PMID- 3096125 TI - Opacification of an optic nerve sheath cystic tumor with intrathecally injected metrizamide. PMID- 3096126 TI - Tapeworm cysts of the cauda equina. PMID- 3096127 TI - Coronary thrombolysis in patients with acute myocardial infarction by intravenous infusion of synergic thrombolytic agents. PMID- 3096128 TI - Electrophysiologic testing of tocainide and mexiletine for ventricular tachycardia: assessment of the need to test both drugs. PMID- 3096129 TI - High-dose mitomycin-C with autologous bone marrow transplantation in patients with refractory malignancies. Influence of dose schedule on pharmacokinetics and nonhematopoietic toxicities. AB - Thirteen courses of high-dose mitomycin-C with autologous bone marrow transplantation (ABMT) were administered to 12 patients. Four dose schedules were evaluated: A) 60 mg/M2 X 1, 60-min infusion; B) 30 mg/M2/day X 2, 15-min infusion; C) 30 mg/M2/day X 2, 60-min infusion; D) 15 mg/M2/day X 4, 60-min infusion. Pharmacokinetic studies using HPLC technique were done in nine patients. All patients have since died and autopsies were performed in nine patients. Two major nonhematopoietic toxicities were encountered and were dose schedule dependent: hemorrhagic colitis (six of six courses in Schedules A and B; two of seven in Schedules C and D), and hepatic dysfunction (five of six in Schedules A and B; two of seven in Schedules C and D). Histopathologic evidence of venocclusive disease of the liver was present in four of five autopsies in Schedules A and B, and two of four in Schedules C and D. One patient died as a result of liver failure associated with submassive hepatic necrosis. Saturation kinetics described by other investigators cannot be confirmed by our pharmacokinetic analyses in nine patients. Severe nonhematopoietic toxicities of mitomycin-C were found at three times the conventional dose; thus, this drug is assessed as not being clinically useful as a single agent in ABMT. PMID- 3096130 TI - The anti-microbial activity, beta-lactamase stability, and disk diffusion susceptibility testing of carumonam (RO 17-2301, AMA-1080), a new monobactam. AB - Carumonam, a new monobactam, was found to have an anti-microbial spectrum similar to aztreonam. Its spectrum includes Enterobacteriaceae, Haemophilus influenzae, pathogenic Neisseria species, Pseudomonas aeruginosa, and some streptococci. Staphylococcus species, enterococci, and many other nonenteric gram-negative bacilli were not inhibited. Enterobacteriaceae resistant to cefoperazone (minimum inhibitory concentrations [MICs] greater than or equal to 32 mg/L) were more likely inhibited by carumonam (52% at less than or equal to 8.0 mg/L) than aztreonam (39%) or ceftazidime (35%). Dilution test methods on agar or in Mueller Hinton broth produced similar results. Carumonam minimum bactericidal concentrations were usually the same or one dilution above the MIC. Carumonam and aztreonam were very stable to most chromosomal (P99, K1, K14) and plasmid mediated beta-lactamases (TEM, OXA, PSE). The Klebsiella oxytoca enzymes hydrolyzed aztreonam at rates greater than or equal to fivefold higher than carumonam but at a rate less than 1% that of cephaloridine. The aztreonam MICs for these Klebsiella stains were greater than or equal to 32 mg/L, but the hydrolysis rates do not fully explain the high-grade resistance to aztreonam. In vitro susceptibility tests with 30-micrograms carumonam disks were found to be very predictive. Similar regression statistics were observed for aztreonam and cefotaxime. Recommendations for carumonam susceptibility testing are susceptible greater than or equal to 21 mm (less than or equal to 8.0 mg/L) and resistant less than or equal to 14 mm (greater than or equal to 32 mg/L). Cross-resistance analysis favors the independent testing of carumonam or aztreonam against gram negative species other than Enterobacteriaceae and P. aeruginosa. PMID- 3096131 TI - Rapid, direct antibiotic susceptibility testing of blood culture isolates using the Abbott Avantage system. AB - The Abbott Avantage (AV) is an updated version of the MS-2 system that provides antibiotic-susceptibility results in four to six hours. Although the system compared favorably with reference methods in several laboratory evaluations, little information exists regarding its performance with inocula obtained directly from blood cultures. The authors compared AV and a modified disk diffusion test using standardized inocula obtained directly from the blood culture bottles for 58 isolates (46 patients). All isolates were also tested by the National Committee for Clinical Laboratory Standards standard disk-diffusion method, using inocula obtained from subcultures of the positive bottles. AV results for 553 antibiotic tests agreed with the direct disk results in 92.6% of the tests, and the agreement with the standard disk results was 88.2%. The concordance between direct and standard disk results was 93.5%. There were 2.2% very major, 1.8% major, and 7.8% minor discrepancies between results obtained with direct AV and standard disk methods. False sensitivity of Klebsiella pneumoniae to ampicillin and carbenicillin and induced clindamycin resistance in staphylococci were noted with AV. When one considers only the clinically meaningful antibiotic-organism combinations, direct AV is an acceptable, rapid alternative to direct disk susceptibility testing. PMID- 3096132 TI - Individual versus public priorities in the determination of optimal vaccination policies. AB - There is a tendency for governments to decide whether or not to offer routine vaccination on the basis of arguments of financial cost, whereas individuals decide whether or not to accept vaccination on the basis of their perception of the risks involved. Furthermore, some vaccines impart, or appear to impart, a degree of indirect protection to nonvaccinated individuals in the community. For both of these reasons, public motives concerning vaccination differ from those of the individual. The quantitative implications of these differences are explored in this paper. It is found that, under a broad range of conditions, rational informed individuals would "choose" a lower vaccine uptake than would the community if it acted as a whole. The result is applied to the pertussis situation in England over the past 30 years and provides a measure of a public's changing perception of the risks associated with that vaccine. PMID- 3096133 TI - Influence of skin site on bioavailability of nitroglycerin ointment in congestive heart failure. AB - Nitroglycerin ointment (12.5 to 50 mg) was administered in randomized fashion to three skin sites, arm, chest, or thigh, to compare the hemodynamic effects and bioavailability in nine patients with severe congestive heart failure. Hemodynamic parameters and arterial nitroglycerin concentrations were measured frequently for 12 hours after each application and for 90 minutes after removal of the ointment. During the study, left ventricular filling pressures decreased from control values of 25.0 +/- 8.6 mm Hg (arm), 25.7 +/- 10.9 mm Hg (chest), and 23.7 +/- 8.4 mm Hg (thigh) to 20.4 +/- 8.6 mm Hg, 20.4 +/- 8.5 mm Hg, and 20.0 +/ 7.5 mm Hg; p less than 0.05, less than 0.01, and difference not significant respectively. Peak nitroglycerin concentrations were 5.1 +/- 4.3 ng/ml (arm), 6.2 +/- 6.0 ng/ml (chest), and 4.1 +/- 6.3 ng/ml (thigh). No significant difference was observed in mean arterial pressure, left ventricular filling pressure, right atrial pressure, or nitroglycerin concentration among the sites. These data show that nitroglycerin ointment has similar bioavailability on the arm, chest, or thigh and therefore can be used interchangeably on these skin sites. PMID- 3096134 TI - Hepatic fibrosis in the mucopolysaccharidoses. AB - The mucopolysaccharidoses are a group of clinically progressive, heritable, lysosomal storage disorders. Many organ systems are affected due to widespread accumulation of incompletely degraded mucopolysaccharide. The novel finding of hepatic fibrosis in each of six cases of mucopolysaccharidosis examined at autopsy (including examples of Hurler syndrome, Hunter syndrome, and Sanfilippo syndrome) is described. In each instance, the liver was diffusely involved by fibrosis that outlined the lobules, and there was extensive hepatocyte and Kupffer cell vacuolization. The pattern of hepatic fibrosis is not explained by either cardiac failure or drug toxicity. It is hypothesized that the hepatic fibrosis is due to the abnormal accumulation of a hepatotoxic metabolite. The frequency and severity of liver disease in the mucopolysaccharidoses deserve further study. In particular, with the advent of bone marrow transplantation as therapy for some of the mucopolysaccharidoses, the question of whether cirrhosis develops in these patients and, if so, what its rate of progression is, should be addressed. PMID- 3096136 TI - Interstitial 7q deletion [46,XY,del (7) (pter----cen::q112----qter)] in a retarded quadriplegic boy with normal beta glucuronidase. AB - A 14-year-old severely retarded male with deletion of chromosomal band 7 cen--- q112 is described. Clinical features include short stature, microcephaly, unusual facies with narrow forehead, short nose, malar hypoplasia, protruding alveolar ridges and incisors, receding chin, relatively long philtrum, and large ears. In addition, he had bilateral inguinal herniae cryptorchidism with hypogonadism, pulmonic stenosis, and spastic quadriplegia. Normal activity of beta glucuronidase was found in the patient's leukocytes. This finding suggests that the gene is not in the deleted region, narrowing the smallest region of overlap to 7q112----q22. PMID- 3096135 TI - Indomethacin and ketanserin block ethchlorvynol-induced hypoxemia in dogs. AB - Intravenous injection of ethchlorvynol (ECV) leads to hypoxemia and a permeability pulmonary edema. Whether the hypoxemia is directly attributable to the pulmonary edema or caused by release of mediators has not been explored. Three groups of dogs were studied: (1) ECV, (2) indomethacin--ECV, and (3) ketanserin--ECV. In group 1, 25 to 30 mg/kg of ECV caused a significant fall in PaO2 at 4 min (92 +/- 12.6 to 77 +/- 21 mm Hg, p less than 0.05), which persisted throughout the experiment. The P(A-a)O2 gradient widened significantly at 3 min (22 +/- 11 to 31 +/- 16.8 mm Hg, p less than 0.05) and remained abnormal for the remainder of the experiment. There was no significant fall in PaO2 in groups 2 and 3. Lung tissue water to dry weight ratio increased significantly in all groups at 60 min. Lung tissue water to dry weight ratios were normal at 10 min after ECV injection in additional groups. It was concluded that ECV causes hypoxemia, which is mediated by cyclooxygenase products and 5 hydroxytryptamine. This hypoxemia can be prevented by the administration of drugs that block these products. PMID- 3096137 TI - Maroteaux-Lamy syndrome in a large consanguineous kindred: biochemical and immunological studies. AB - We describe a large consanguineous German-Acadian ("Cajun") family from a rural area in Louisiana in which 11 persons in two generations had the Maroteaux-Lamy syndrome. The mutant arylsulfatase B enzyme in this family was similar to the mutant enzyme in previously studied families in its cross-reactivity with specific antibodies to the enzyme, but it differed in both its electrophoretic mobility and its residual enzymatic activity. These findings indicate that a different mutational event leading to Maroteaux-Lamy syndrome occurred in this family. PMID- 3096138 TI - Dermatoglyphics and creases in patients with neurofibromatosis von Recklinghausen. AB - Fingerprint and palmar dermatoglyphics and creases were investigated in 60 patients (20 males and 40 females) with generalized neurofibromatosis. Like previous investigators, we found a significantly increased frequency of digital central pocket patterns. Furthermore, affected males and females had an increased frequency of monocentric whorls (P = 0.0037), higher quantitative values on digit II of both hands (P = 0.04), more often a reduction of main line C (P less than 0.05) with decreased frequencies of patterns in the 3rd and 4th interdigital area of the left hand (P less than 0.05), and a lower ab ridge count (males P less than 0.005; females P less than 0.001) than control individuals. On the right hand of males the frequency of high endings (5' or 5'') of line A was decreased (P less than 0.05). A significantly increased frequency of Sfl (Sydney line) was found in female patients (P less than 0.001). Male and female patients often showed a high number of secondary creases (P less than 0.001). PMID- 3096139 TI - Are the Mirhosseini-Holmes-Walton syndrome and the Cohen syndrome identical? PMID- 3096140 TI - Maculopathy associated with combination chemotherapy and osmotic opening of the blood-brain barrier. AB - Eleven patients with intracranial malignant neoplasms underwent hyperosmotic opening of the blood-brain barrier by rapid mannitol infusion via the internal carotid or vertebral artery. Cyclophosphamide was administered intravenously preceding the mannitol infusion and methotrexate was infused after the mannitol via the same artery. Both the mannitol and methotrexate delivered via the carotid artery have direct access to the ipsilateral choroidal and retinal circulations. In these patients, retinal pigment epithelial changes eventually developed ipsilateral to the carotid infusions. The changes probably represent the toxicity of intraarterial methotrexate possibly potentiated by mannitol-induced opening of the blood-retinal barrier. Functional visual loss was minimal and was not a limiting factor with this therapeutic modality. PMID- 3096141 TI - Diabetes mellitus in the BB/W rat. Insulitis in pancreatic islet grafts after transplantation in diabetic recipients. AB - Spontaneous diabetes mellitus in the BioBreeding/Worcester (BB/W) rat is preceded by lymphocytic insulitis which destroys pancreatic beta cells. Cultured major histocompatibility complex identical pancreatic islets and adrenal cortex derived from diabetes-resistant BB/W donors were transplanted into diabetic recipients with hyperglycemia of variable duration. Islet grafts were the targets of BB/W immune attack and revealed lymphocytic insulitis after transplantation into diabetic recipients even in the absence of insulitis within endogenous pancreatic islets. These findings suggest that the BB/W immune attack on pancreatic beta cells can recur in islet grafts long after the onset of the diabetic syndrome. PMID- 3096143 TI - An archaic character in the Broken Hill innominate E. 719. AB - The additional hominid material from Broken Hill, Kabwe, Zambia, is only dubiously associated with the hominid cranium from the site and is often considered to be anatomically modern in morphology. This study identifies an archaic feature, previously recognised in Pliocene and earlier Pleistocene innominates, in the Broken Hill innominate E. 719. An acetabulocristal buttress of cortical bone 10 mm thick is present, and this can be clearly distinguished from the morphology present in a comparative sample of large recent Homo sapiens innominates. This observation increases the likelihood that some of the additional specimens from Broken Hill are indeed of comparable antiquity to the hominid cranium and extends the range of hominids in which the feature has been recognised. PMID- 3096142 TI - Genetic variation within and among lion tamarins. AB - The golden lion tamarin Leontopithecus rosalia rosalia, one of the rarest and most endangered of New World primates, has been the focus of an intensive research and conservation effort for two decades. During that period, managed breeding from 44 founders has brought the captive population to over 400 individuals, a number that equals or exceeds the estimated number of free-ranging golden lion tamarins. The extent of genetic variation among golden lion tamarins was estimated with an electrophoretic survey of 47 allozyme loci from 67 captive and 73 free-ranging individuals. The amount of variation was low, compared to 15 other primate species, with 4% of the loci being polymorphic (P), and with an average heterozygosity H estimate of 0.01 in these callitrichids. Electrophoretic analyses of captive and free-ranging animals (N = 31) of two allopatric morphotypes, Leontopithecus rosalia chrysopygus and L. r. chrysomelas, were similar to the L. r. rosalia findings insofar as they also revealed limited genetic polymorphism. Computation of the Nei-genetic distance measurements showed that the three morphotypes were genetically very similar, although discernible differentiation had occurred at two loci. These data are consistent with the occurrence of recent reproductive isolations of these subspecies. PMID- 3096144 TI - Continuous versus single bolus enteral nutrition: comparison of energy metabolism in humans. AB - Continuous respiratory exchange measurements were performed on five women and five men for 1 h before and 6 h after the administration of a milkshake (53% carbohydrates, 30% lipid, and 17% protein energy) given either as a single bolus dose or continuously during 3 h using a nasogastric tube. The energy administered corresponded to 2.3 times the postabsorptive resting energy expenditure. Resting energy expenditure, respiratory quotient, plasma glucose, and insulin concentrations increased sooner and steeper, and plasma free fatty acids levels decreased earlier with the meal ingested as a single dose than with continuous administration. The magnitude of nutrient-induced thermogenesis was greater (P less than 0.01) with the single dose (means +/- SE, 10.0 +/- 0.6%) than with the continuous administration (8.1 +/- 0.5%). The overall (6 h) substrate balances were not significantly different between the two modes of administration. It is concluded that the mode of enteral nutrient administration influences the immediate thermogenic response as well as changes in respiratory quotient, glycemia, and insulinemia; however, the overall nutrient balance was not affected by the mode of enteral nutrient administration. PMID- 3096145 TI - Effects of TRH on thyrotroph function and number in rat pituitaries transplanted to renal capsule. AB - We investigated the function of thyrotrophs in rat pituitaries that were transplanted under the renal capsule of 3-wk-old male Sprague-Dawley rats, which were either intact or hypophysectomized. Groups of 12 animals were implanted with osmotic minipumps that delivered a constant infusion of either thyrotropin releasing hormone (TRH; 1 mg X kg-1 X day-1) or normal saline for 1 wk. In hypophysectomized rats, TRH infusion led to the appearance of substantial amounts of biologically active serum TSH and prevented the hypothyroidism that occurred in the control group. However, TRH did not change the transplant contents of DNA, immunoactive TSH, and mRNA levels for TSH subunits. Comparison of sellar and renal pituitary tissues, obtained from intact rats after 1 wk of either saline or TRH infusion, showed that removal of the pituitary from hypothalamic influence resulted in a 90% depletion of the thyrotroph TSH content. TRH infusion depleted only 63% of the TSH content of sellar thyrotrophs. The mRNA levels for TSH beta subunit were similar in sellar and transplanted pituitaries and did not significantly change after TRH infusion. When immunocytochemically stained using rat TSH antiserum, the thyrotrophs in pituitary transplants were morphologically and numerically indistinguishable from the thyrotrophs in sellar pituitaries, in the presence or absence of TRH. These data indicate that in transplanted pituitary, for up to 1 wk of a constant infusion, TRH does not significantly affect either the number of thyrotrophs or their ability to synthesize TSH subunit mRNA. However, it is required to maintain released TSH in circulation, since TSH levels were low in the absence of TRH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096146 TI - Extremity amino acid metabolism during starvation and intravenous refeeding in humans. AB - This study was designed to evaluate peripheral tissue amino acid metabolism in normal subjects who underwent starvation followed by intravenous administration of a nutritional repletion regimen with varying nonprotein caloric sources. Extremity amino acid (AA), arteriovenous differences, and blood flow were measured across forearm and/or leg of 12 healthy male subjects. Plasma AA flux [(arterial concentration - venous concentration) X flow X (1 - hematocrit); ml X min-1 X 100 ml tissue-1] was determined postabsorptively (PA), after 10 days of starvation (ST) and on the 10th day of intravenous feeding (IVF). There was a significant (P less than 0.05) decrease in efflux of total amino acids during the starvation study (-345 +/- 74) compared with the PA study (-1,463 +/- 263). Peripheral tissue AA uptake increased significantly (P less than 0.05) after 10 days of IVF (+276 +/- 79) compared with both PA and ST studies. There were no significant differences in extremity AA flux between those subjects who received 100% dextrose and those receiving 50% dextrose-50% lipid as a nonprotein caloric source. Linear relationships of AA infusion rate (IR) to AA flux (r = 0.845, P less than 0.001) and AA IR to [AA]art IVF (r = 0.842, p less than 0.001) were observed during IVF. Results of this study suggest that extremity flux determinations during IVF cannot be interpreted without correction for AA availability as reflected by AA infusion rate. PMID- 3096147 TI - Expression of amino acid and peptide transport systems in rat small intestine. AB - Quantitative autoradiography was used to measure the distribution of transport of leucine, lysine, and glycyl-L-leucine along the villus of the rat jejunum. A comparison was made between normal juvenile animals and ones maintained on a 5% protein isocalorific diet. Uptake of leucine, lysine, and glycyl-L-leucine was confined to the top 150 microns of the villus in control animals and initial expression of transport corresponded to a cell age of 32 h. The low-protein diet altered the distribution of transport in the same way for all three substrates, but although the position up the villus of the initial expression of transport was altered, transport always appeared in cells 32 h old. These data indicate that the age of intestinal epithelial cells is an important determinant of their ability to transport amino nitrogen. Transport kinetic data indicated that peptide uptake was initially elevated in response to the low-protein diet while free amino transport was depressed. It is concluded that a second locus of control determines the amount of transport expressed per individual cell. PMID- 3096148 TI - Functional role of carbonic anhydrase in intestinal electrolyte transport. AB - We examined the role of carbonic anhydrase activity in intestinal transport by measuring the effect of systemic pH and PCO2 on electrolyte transport in the presence and absence of luminal acetazolamide. Adult Sprague-Dawley rats were anesthetized, and ileal and colonic segments were perfused with Ringer solution that was acetazolamide-free or that contained 0.1 mM sodium acetazolamide. Consecutive states of acute respiratory alkalosis and acidosis were created by changing the inspired CO2 from 0% (room air) to 8% CO2. In the ileum, acetazolamide perfusion did not affect the increment in net sodium and chloride absorption caused by a reduction in systemic pH. Mucosal carbonic anhydrase activity in this segment was measurable, although very low. In both the ascending and descending colon, acetazolamide perfusion reduced the increment in net sodium absorption caused by an increase in systemic PCO2. In addition, acetazolamide increased the chloride absorptive response to PCO2 in the ascending colon but did not affect the chloride response at all in the descending colon. Colonic mucosal carbonic anhydrase exhibited a proximal-to-distal gradient of activity: levels in the ascending colon were severalfold greater than in the descending colon. These findings suggest a functional role for carbonic anhydrase in mediating the colonic but not the ileal absorptive response to changes in systemic acid-base balance. PMID- 3096149 TI - Effects of medium pH on duodenal and ileal calcium active transport in the rat. AB - To study the effect of pH on Ca active transport in vitro pH was varied from 7.1 to 7.7, and bidirectional transmural Ca fluxes were measured under short circuited conditions across duodenum or ileum from rats fed either normal chow (NCD, 1.2% Ca) or low Ca (LCD, 0.002% Ca). Duodenum and ileum from rats fed LCD actively absorbed calcium at medium pH 7.4. Reduction in mucosal and serosal medium bicarbonate from 25 to 10 mM (pH 7.4 to 7.1) decreased duodenal net Ca absorption (Jnet) from 121 +/- 32 to 39 +/- 9 nmol X cm-2 X h-1 (P less than 0.02) and ileal Jnet from 74 +/- 13 to 22 +/- 6 (P less than 0.01). The decline in duodenal and ileal Ca Jnet was due to a decrease in the mucosal-to-serosal flux (Jm----s). Raising medium pH from 7.4 to 7.7 by increasing bicarbonate from 25 to 50 mM did not alter Ca Jm----s, serosal-to-mucosal flux (Js----m), or Jnet X Ca fluxes across ileum from rats fed NCD demonstrated net secretion. LCD ileal Jm----s was unaltered when pH was reduced from 7.4 to 7.1 by increasing the PCO2 content of the buffer from 30 to 81 mmHg while maintaining bicarbonate at 24 mM. The results indicate that in vitro conditions that simulate metabolic acidosis (low bicarbonate and pH, normal PCO2) inhibit 1,25D-mediate calcium Jm----s, whereas conditions that simulate respiratory acidosis have no effect on Ca fluxes. The present studies suggest that decreases in calcium Jm----s is by a primary alteration in transport of other ions rather than direct effect on Ca transport. PMID- 3096150 TI - Effects of parathyroid hormone and urinary phosphate on collecting duct hydrogen secretion. AB - Urine-minus-blood PCO2 (U - B PCO2) during alkaline diuresis (urinary pH greater than 7.8) was determined in paired experiments using bicarbonate-loaded rats to assess the effects of parathyroid hormone (PTH) and urinary phosphate concentration [( Pi]u) on collecting duct H+ secretion. U-B PCO2 was higher for any value of urinary bicarbonate concentration ([HCO3]u) in the presence of PTH [intact rats and thyroparathyroidectomized (TPTX) PTH-infused rats] than in its absence (calcium-infused intact rats and TPTX rats). However, when [Pi]u was maintained constant by prior phosphate infusion, PTH administration in TPTX rats failed to elevate U-B PCO2. When PTH was infused in TPTX rats to maintain constant the plasma PTH level, subsequent phosphate infusion increased [Pi]u and elevated U-B PCO2 for any value of [HCO3]u. Moreover, when the data were pooled, there was a positive linear relationship between U-B PCO2 factored for [HCO3]u and [Pi]u (P less than 0.001). In all experiments, other factors that may affect U-B PCO2, such as plasma acid-base status, urinary osmolality, and extracellular fluid volume, did not vary. We conclude that PTH stimulates collecting duct H+ secretion indirectly via the increase in [Pi]u. PMID- 3096151 TI - Effects of gluco- and antiglucocorticoids on renal and aortic prostaglandin synthesis. AB - The effects of glucocorticoid agonists RU 26988 (G) and dexamethasone (D) and antagonist RU 486 (AG) on aortic and renal prostaglandin (PG) production were studied in Wistar rats. Blood pressure increased in rats administered G (20 mg X kg-1 X day-1) during 1 or 3 days; such increase was prevented by AG (100 mg X kg 1 X day-1). Renal papillary PGE2 release was increased after a 3-day administration of G, and this was prevented by AG. Neither G nor AG altered basal 6-keto-PGF1 alpha aortic production. However, G inhibited and AG magnified the stimulatory effect of ionophore A 23187, added in vitro, on 6-keto-PGF1 alpha production; AG reversed G inhibition. In addition, AG alone (20 mg X kg-1 X day-1 X 3 days) enhanced the stimulatory effect of angiotensin II (10(-8) M), added in vitro, on 6-keto-PGF1 alpha release. In vitro studies were performed on renomedullary interstitial cells grown in culture; G and D depressed PGE2 production in a dose-dependent manner; AG at equimolar 10(-8) M concentration inhibited this effect. In conclusion, AG inhibits the effects of G on blood pressure and PG synthesis. G exerts strong depressor activity on in vitro PGE2 renal production, whereas in vivo effects are more complex. Endogenous G inhibits aortic prostacyclin production, an action unmasked by AG administration. Diminished stimulation of vascular prostacyclin synthesis may contribute to vascular hyperreactivity in G-induced hypertension. PMID- 3096152 TI - A new microelectrode method for simultaneous measurement of pH and PCO2. AB - A liquid-membrane pH-PCO2 microelectrode is described for the simultaneous measurement of pH and PCO2 in tissues and body fluids. The microelectrode is simple and easy to fabricate. It can be used to measure HCO3 concentration in solutions at chemical equilibrium. In the physiological range the microelectrode response is linear with nearly Nernstian slopes for PCO2 (61.2 +/- 2.0 mV/log10 PCO2) and pH (63.7 +/- 1.9 mV/pH units) (n = 14) at 37 degrees C. The PCO2 response is independent of the solutions' pH, anionic composition, and presence of serum proteins. In randomly micropunctured rat surface proximal tubules, pH averaged 6.80 +/- 0.04 and PCO2 averaged 57.7 +/- 4.6 mmHg (n = 22), whereas in the adjacent peritubular capillaries pH was higher (7.27 +/- 0.03) but PCO2 was not different (55.7 +/- 4.6 mmHg) (n = 22). Systemic arterial PCO2 was significantly lower compared with the renal cortex and averaged 37.4 +/- 2.4 mmHg (n = 14). Directly measured and pH-PCO2 microelectrode-derived HCO3 concentrations in systemic arterial blood, surface fluid bathing the kidney, and randomly micropunctured proximal tubules were approximately equal. PMID- 3096153 TI - Oxygen binding in alligator blood related to temperature, diving, and "alkaline tide". AB - Blood of Alligator mississippiensis has a relatively high O2 affinity, the half saturation O2 tension (P50) = 24.5 Torr at pH 7.495, the arterial, normocapnic pH at 25 degrees C. Although the overall temperature sensitivity of P50 at 15, 25, and 35 degrees C and constant pH is low, the effect on P50 almost doubles when measured at the in vivo pH of each temperature (delta Happ = -24 and -47 kJ/mol, respectively). The CO2 Bohr effect (theta CO2 = -0.95) is 5.5 times greater than the fixed acid Bohr effect (theta FA), and the Haldane effect is small (approximately 0.03 pH units). The relatively high O2 affinity may ensure efficient utilization of the lung O2 reserve during breath holding and diving, whereas its pronounced in vivo temperature sensitivity may be adaptive to the high temperature quotients of the organismic O2 requirement. The large difference between theta CO2 and theta FA will favor constancy in blood O2 affinity in the face of large activity-induced increases in blood lactate and pronounced feeding induced alkaloses. These "alkaline tides," which result from an exchange of plasma Cl- for HCO-3 across the gut wall, appear to be only slightly compensated by increased blood CO2 tensions. The results are additionally discussed in terms of allosteric modulation of hemoglobin-O2 affinity in crocodilians. PMID- 3096154 TI - Effects of lung volume and O2 and CO2 content on cutaneous gas exchange in frogs. AB - The effects of lung O2 and CO2 content and volume on cutaneous gas exchange and perfusion were investigated in the frog, Rana pipiens. (Ha)-anesthetized frogs were equilibrated with 9.5% Freon-22 (Fr, chlorodifluoromethane) and 1.1% Ha. Cutaneous elimination of Fr, Ha, and CO2 into a small sample chamber on the abdomen was measured with a mass spectrometer. Introducing an air mixture into the lung decreased cutaneous Fr, Ha, and CO2 elimination. Lung inflation with an O2 mixture decreased cutaneous gas elimination more than with the air mixture. Inflation with a N2 mixture had no effect. The response to lung inflation with the air mixture was not affected by adding 4.8% CO2 to the air mixture or by atropine. Voluntary lung ventilation decreased CO2 and Fr elimination. The results indicate that intrapulmonary O2 is a factor regulating skin breathing. If a change in lung volume is also a factor, it requires a concomitant change in lung O2. Intrapulmonary CO2 and cholinergic nerves are not involved in cutaneous respiration across the abdomen. PMID- 3096155 TI - Variability of response to lithium augmentation in refractory depression. AB - Eighty-four patients with major depression refractory to a controlled antidepressant trial had lithium added to their ongoing treatment. Objective symptom ratings showed highly significant improvement in the sample as a whole. At discharge or after 24 days, 31% of the patients showed a marked response, 25% a partial response. Thus, 56% of patients had a significant positive response, while 44% were nonresponders. This study indicates that response to lithium augmentation may be quite variable and a 3-week trial is necessary to assess full benefit. PMID- 3096156 TI - Combined carbamazepine and lithium therapy for violent behavior. PMID- 3096157 TI - A study of the biological behavior of the meniscus as a transplant in the medial compartment of a dog's knee. AB - A surgical procedure was developed such that a meniscus could be reimplanted in the medial compartment of canine knees. The medial meniscus was removed and reimplanted in one group of seven animals, removed and reimplanted with a glutaraldehyde-preserved bioprosthesis in a second group of five animals, and removed and replaced by an allograft meniscus preserved 2 to 3 weeks in tissue culture in a final group of ten animals. All animals were autopsied at 2 months and the knees were examined by gross dissection and histologic study of the joint capsule meniscal interface. Results showed that implantation by the surgical technique was effective and no loose bodies or partial detachments were found in the reimplantation or tissue culture-stored allogenic menisci. Allogenic menisci preserved in glutaraldehyde and termed a bioprosthesis attached to the joint capsule less satisfactorily. There was minimal inflammation of the synovium in any group at 2 months; however, the glutaraldehyde group showed repeated effusions at 1 and 2 weeks. PMID- 3096158 TI - High-grade epithelioid angiosarcoma of the scalp. An immunohistochemical and ultrastructural study. AB - The ultrastructural and immunohistochemical characteristics of a high-grade epithelioid angiosarcoma of the scalp are reported. By light microscopy, the neoplasm simulated a poorly differentiated carcinoma, either primary or metastatic from some occult site. Immunohistochemical study, using a specific antibody against factor VIII-related antigen, was positive when direct immunofluorescence was applied to frozen specimens of the neoplasm. Application of immunoperoxidase (avidin-biotin complex method) on paraffin-embedded tissue using the same antibody was negative. Ultrastructually, the neoplasm had a prominent cytoskeleton of intermediate filaments, numerous pinocytotic vesicles, small intercellular lumina with microvilli on their surfaces, and characteristic intracytoplasmic vacuoles. A brief discussion of the differential diagnostic features is made. PMID- 3096159 TI - Malignant angioendotheliomatosis proliferans. Report of an autopsied case studied with immunoperoxidase. AB - We report the autopsy findings in a case of malignant angioendotheliomatosis proliferans. Neoplastic cells stained positively for leukocyte common antigen, factor VII-related antigen, and IgG by the indirect peroxidase-antiperoxidase technique. The authors speculate that malignant angioendotheliomatosis proliferans represents a distinctive type of neoplasm that appears either to exhibit bidirectional lymphoid and endothelial differentiation or to consist of an heterogeneous population of cells. PMID- 3096160 TI - Primary angiosarcoma of the gingiva. Case report with immunohistochemical study. AB - A case of angiosarcoma involving primarily the gingiva in an 86-year-old woman is reported. The neoplasm was strongly positive for factor VIII-related antigen, negative for cytokeratins, and positive for vimentin, confirming the vascular nature of the tumor. The patient died from heart failure 1 month after surgical excision of the lesion without clinical evidence of metastasis. PMID- 3096161 TI - [Zenker's diverticulum. Apropos of a case]. PMID- 3096162 TI - Respiratory depression after morphine in the elderly. A comparison with younger subjects. AB - The effects of intravenous morphine (10 mg/70 kg) on the ventilatory response to CO2 were studied in two groups of subjects, young (18-29 years) and old (66-85 years), prior to elective surgery. In both groups morphine caused a significant depression of respiration as judged by a reduction in the slope of the CO2 response curve, a reduction in the calculated ventilation at an end tidal CO2 tension of 7.3 kPa, a rise in resting end tidal CO2 and a rise in the CO2 threshold. There were no significant differences between the two groups in the changes produced by the drug, suggesting that acute respiratory depression after a single intravenous injection of morphine is similar in old and young people. PMID- 3096163 TI - Gas sampling from a facemask for capnography. PMID- 3096164 TI - [Lung compliance in man is impaired by the rapid injection of alfentanyl]. AB - To demonstrate opioid-induced muscular rigidity, compliance was measured in patients after induction of anaesthesia with etomidate (0.3 mg/kg) and N2O/O2 (2:1) ventilation. Alfentanil was given subsequently to two groups of patients: either as a bolus injection (n = 15) over 3 s, or as a slow injection (n = 15) over 30 s. Significant reduction of compliance (max. 30%) was observed after rapid injection in the following 4 min. This effect was promptly reversed by succinylcholine (25 mg i.v.). The slow injection of the opioid over 30 s, was followed by a small insignificant reduction in compliance. Alfentanil is increasingly used for short-term anaesthesia where no muscle relaxants are administered. Thus slow injection of the opioid is advised in order not to impair adequate ventilation. PMID- 3096165 TI - Determination of ADP-ribosyl arginine anomers by reverse-phase high-performance liquid chromatography. AB - A simple and rapid method for the determination of ADP-ribosyl arginine anomers was devised. Analysis is performed by reverse-phase high-performance liquid chromatography on a 5-micron Cosmosil 5C18 column and uv detection. ADP ribosylation of arginine by hen liver ADP-ribosyl-transferase and the effect of pH on anomerization are also presented. PMID- 3096166 TI - Carbohydrate mapping by mass spectrometry: a novel method for identifying attachment sites of Asn-linked sugars in glycoproteins. AB - A new method is described for locating the specific sites of attachment of Asn linked carbohydrates in glycoproteins. The molecular weights of peptides released from the glycoprotein with proteases of known specificity are determined by fast atom bombardment mass spectrometry and fitted to the known or DNA-derived sequence. Oligosaccharides attached to Asn are released either before or after proteolysis with a glycosidase, usually peptide: N-glycosidase F, an enzyme that cleaves the beta-aspartylglycosylamine linkage of all known types of Asn-linked sugars and converts the attachment-site Asn to Asp. New peaks appearing in the mass spectra after treatment with glycosidase correspond to formerly glycosylated sites. Conversely, signals which disappear after glycosidase treatment correspond to glycopeptides. The differences in mass between these sets of signals define the composition of the carbohydrate at the given site in terms of deoxyhexose, hexose, N-acetylhexosamine, and sialic acid content. The extent of glycosylation at a given site can be estimated from the ratio of the peak heights corresponding to the Asn- vs Asp-containing peptides which differ by 1 Da in mass. This rapid and sensitive (low nmol) technique is illustrated here for ribonuclease B and for tissue plasminogen activator, a multiply glycosylated glycoprotein. PMID- 3096167 TI - Effects of phenobarbital on cerebral blood flow and metabolism in young and aged rats. AB - The cerebrovascular and cerebral metabolic changes produced by intraperitoneal injection of phenobarbital (50, 150, and 250 mg/kg) were studied in young adult (6-month) and senescent (28-month) Wistar rats. Cerebral blood flow (CBF) was measured using radioactive microspheres and cerebral oxygen consumption (CMRO2) was obtained by multiplying cortex CBF by the arterial-sagittal sinus oxygen content difference. Control values for blood pressure, blood gas tensions, CBF, and CMRO2 were similar in the young and aged animals during 70% N2O/30% O2. Intraperitoneal phenobarbital produced dose-dependent decreases in CBF with no significant difference between young and aged rats at each phenobarbital dose. At the highest phenobarbital dose (250 mg/kg) CBF was reduced by 49% in the young rats and 52% in the aged rats (P greater than 0.10). CMRO2 was also depressed in a dose-dependent fashion in both young and aged animals with each phenobarbital dose. However, the decrease produced by the highest phenobarbital dose was significantly greater in the aged rats (55%) than the young rats (43%, P less than 0.05), even though the EEG was isoelectric in both groups. The difference in CMRO2 between young versus aged rats at a time when the EEG is isoelectric suggests that high-dose phenobarbital may depress nonelectrical cerebral metabolic processes more in aged rats. PMID- 3096168 TI - [Sarcocystis alceslatrans (Apicomplexa) from a palaearctic elk (Ruminantia)]. AB - Sarcocysts from a palaearctic moose have been studied for the first time by light and electron microscopy. Because of coincidences in morphology of the cysts, especially of the cyst wall structure and the cystozoides, with the North American species Sarcocystis alceslatrans DUBEY, 1980, they are assigned to this species. PMID- 3096169 TI - [Surgery and the acquired inhibitor of factor VIII coagulant]. AB - A case is reported of an 80 year old woman with old sarcoidosis and acquired factor VIIIc inhibitor undergoing orthopaedic surgery. This was successfully carried out after she had been given a total of 48,420 units of factor VIII concentrate: there were no haemorrhagic complications. The main pathological states in which acquired factor VIIIc inhibitor may be found are related: principal treatments available nowadays are discussed: immunosuppressors, human factor VIII, animal factor VIII, prothrombin complex concentrate, plasma exchange. PMID- 3096170 TI - [Spinal cord toxicity of lysine acetylsalicylate and ketamine hydrochloride administered intrathecally in the rat]. PMID- 3096172 TI - Identification of Brucella abortus in formalin-fixed, paraffin-embedded tissues of cows, goats, and mice with an avidin-biotin-peroxidase complex immunoenzymatic staining technique. AB - An avidin-biotin-peroxidase complex immunoenzymatic staining technique was evaluated for light microscopic detection of Brucella organisms in formalin fixed, paraffin-embedded tissues. Tissues from cows, goats, and mice inoculated with B abortus strain 2308 were examined, using rabbit antiserum to Brucella cell surface protein as primary antibody. Stained organisms were identified histologically in tissue sections containing B abortus, as detected by bacteriologic examination of duplicate nonprocessed tissue samples. Bacillus sp, Corynebacterium pyogenes, Escherichia coli, Listeria monocytogenes, Pasteurella haemolytica, P multocida, Salmonella typhimurium, Staphylococcus sp, and Streptococcus sp did not stain with this system, using anti-Brucella cell surface protein primary antibody, thus indicating specificity for Brucella organisms. PMID- 3096171 TI - Mode of admission and cost for surgical DRGs. AB - The purpose of this study was to confirm the hypothesis that emergency department admissions were more expensive than their nonemergency counterparts per diagnosis related group (DRG) and to see if this characteristic was displayed across many hospitals. All surgical admissions (N = 39,682) to the 11 acute-care hospitals of the New York City Health and Hospitals Corporation were analyzed during an 18 month period to yield a study population (N = 26,569) of matched DRG subgroups (ED vs nonED) at each hospital of at least five patients per variable for that particular DRG. A cost-per-patient analysis was conducted for each admission. Total costs for the study population were $163,360,636. A total of 75.8% of surgical admissions (N = 20,143) were admitted in DRGs in which ED admissions were more costly than their nonED-matched counterparts. The following was the trend in percentage of total specialty admissions in DRGs in which ED admissions were more costly than nonED admissions: urology (88.4%); ear, nose, and throat (86.2%); general and vascular (80.1%); cardiothoracic (78.0%); orthopedics (75.6%); plastic surgery (62.1%); neurosurgery (60.5%); and ophthalmology (46.0%). Route of admission (ED vs nonED) was an identifier of higher-cost patients per DRG across hospitals in a large public hospital system. These data demonstrate that hospitals with substantial numbers of surgical ED admissions may face significant financial risk under DRG reimbursement, and suggests that the DRG system does not adequately compensate hospitals for the higher cost of the emergency surgical admission. PMID- 3096173 TI - Coagulation assays and platelet aggregation patterns in human, baboon, and canine blood. AB - Coagulation assays in citrated plasma and platelet-aggregation patterns in citrated platelet-rich plasma were performed, using human, baboon, and canine blood. Similar fibrinogen concentrations, factor VIII antihemolytic factor (AHF) clotting protein concentrations, and thrombin times were seen in human and baboon plasma, whereas prothrombin times and activated partial thromboplastin times were significantly (P less than 0.017) more prolonged in baboon plasma than in human plasma. Canine plasma had significantly lower prothrombin times, activated partial thromboplastin times and thrombin times, and significantly higher concentrations of fibrinogen and factor VIII (AHF) clotting protein than did human plasma. The baboon factor VIII antigen cross-reacted with an antibody against human factor VIII antigen, whereas the canine factor VIII antigen did not. Human and canine platelets had similar aggregation patterns to adenosine diphosphate (ADP), whereas baboon platelets were less responsive to ADP than were human platelets. The response to collagen-induced aggregation in human and baboon blood was similar at concentrations of 0.190, 0.100, 0.050 and 0.025 mg/ml, whereas the response in human and canine blood was similar at concentrations of 0.190, 0.100, and 0.050 mg/ml. The lag time before aggregation with collagen was 2 to 3 times longer for canine platelets than for human platelets; human and baboon platelets had similar lag times. Baboon platelets were more responsive to arachidonic acid than were human platelets at concentrations of 0.25, 0.12, and 0.06 mg/ml, whereas canine platelets were less responsive than were human platelets at the highest concentration of 0.5 mg/ml. Human platelets were more responsive to epinephrine than were baboon or canine platelets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096174 TI - Chromatographic separation and characterization of Pasteurella haemolytica cytotoxin. AB - Biochemical and immunologic properties of the cytotoxin (leukotoxin) produced by Pasteurella haemolytica were examined. Crude, bacteria-free supernatants from logarithmic phase P haemolytica were fractionated, using a series of column chromatographic techniques. Sequential anion exchange chromatography, gel filtration chromatography, and chromatofocusing resulted in a cytotoxic substance (cytotoxin-C) of approximately 160 kilodaltons (kD), as determined by use of gel filtration chromatography. Polyacrylamide-gel electrophoresis of cytotoxin-C yielded 3 protein bands with relative mobilities of 0.37, 0.42, and 0.63. On the basis of immunoblotting with a cytotoxin-neutralizing bovine immunoglobulin for antigen detection, the 2 low-mobility bands shared a strong region of immunogenicity. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, principal protein constituents of cytotoxin-C were found at 160, 66, 57, and 23 kD. Using immunoblotting with cytotoxin-neutralizing immunoglobulin, strong, distinct reactions with the 66- and 57-kD bands were detected. Immunization of rabbits and mice with cytotoxin-C resulted in sera that reacted strongly with cytotoxin-C in enzyme-linked immunosorbent assays and immunodiffusion assays. The major immunogenic proteins also were detected by use of immunoblotting with anticytotoxin-C sera from rabbits and mice. Postinoculation rabbit sera neutralized crude cytotoxin. PMID- 3096175 TI - Immune interferon is a growth factor for human lung fibroblasts. AB - A number of immunologically mediated lung disorders are characterized by the presence of fibrosis. In these studies, we demonstrate that immune (gamma) interferon, as well as interleukin-1 (IL-1), can function as a growth factor for human lung fibroblasts. Interleukin-2 has no effect on the proliferation of these cells. Interferon increases the proliferation of lung fibroblasts in a dose dependent manner and functions as a progression factor by complementing the growth-promoting effects of a characterized competence factor such as fibroblast growth factor. These observations suggest that interferon, as well as IL-1, may play an important role in the fibrotic response as well as the immune response in the lung. PMID- 3096176 TI - Demonstration of intrapleural immunoglobulin synthesis by agarose gel isoelectric focusing. A new specific method for the diagnosis of pleural effusions of inflammatory origin? AB - In order to demonstrate an intrapleural immunoglobulin (Ig) synthesis, pleural effusions and serum from 14 patients with pleural effusions of various causes (inflammatory condition, malignancies, primary lung cancers, pleural metastasis, and congestive heart failure) were investigated by agarose gel isoelectric focusing (AIEF), antiserum immunofixation with monospecific antiserum against IgG and IgA, and quantitative estimation of IgG and IgA. Intrapleural immunoglobulin synthesis was assumed to occur in patients with oligoclonal Ig limited to the pleural compartment or in patients with a raised IgG index, equal to (pleura/serum IgG):(pleura/serum albumin), or a raised IgA index, equal to (pleura/serum IgA):(pleura/serum albumin). Two of 3 patients with rheumatoid pleuritis had a polyclonal intrapleural immunoglobulin synthesis demonstrated by the presence of a raised IgG and IgA index without any signs of oligoclonal Ig production on AIEF. Two of 3 patients with assumed tuberculous pleuritis had, despite a normal IgG and IgA index, an oligoclonal intrapleural IgG production detected by AIEF. This oligoclonal reaction was shown by absorption studies with Mycobacterium tuberculosis antigen to be directed against M. tuberculosis. No signs of intrapleural immunoglobulin synthesis were found in the other 10 patients investigated. PMID- 3096177 TI - The inspiratory workload of patient-initiated mechanical ventilation. AB - We quantified inspiratory effort during patient-triggered ventilator cycles in 20 critically ill patients receiving assisted mechanical ventilation (AMV). An index of the patient's work per liter of ventilation (WP) was defined as the difference in the mechanical work done by the ventilator during controlled and assisted breathing cycles at similar settings of tidal volume and flow. WP was estimated graphically from plots of airway pressure against inflation volume for peak flow settings of 60 L/min and 100 L/min. During patient-initiated cycles, effort did not cease with the onset of gas delivery. Values for WP varied widely but at both flow settings frequently equalled or exceeded the total workload expected for a spontaneously breathing normal subject. Furthermore, the patient's component of the mechanical workload during AMV was often a large percentage of the work performed during spontaneous breathing 30 s after discontinuing ventilator support (at 60 L/min: mean 62.6%; range 30.3 to 116.3%). The addition of deadspace to the external circuit increased VE and WP significantly. Both the maximally negative pressure generated against an occluded airway and the deflection of esophageal pressure in the first 100 ms after the onset of inspiratory effort were highly correlated with WP, suggesting the importance of strength and ventilatory drive as determinants of patient effort. WP correlated poorly with measures of chest mechanics, and there was no separation of WP values for the two flow rates we studied, perhaps because both settings exceeded the patient's spontaneous demand for airflow (FD).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096178 TI - The effect of chronic nocturnal oxygen administration upon sleep apnea. AB - Administration of nocturnal oxygen for 1 night to patients with obstructive sleep apnea (OSA) causes a moderate reduction in apnea frequency without improving hypersomnolence. Therefore, we administered oxygen chronically to patients with OSA to determine: whether apnea frequency would be further reduced, whether the effect of oxygen upon apnea frequency is correlated with an increased ventilatory response to hypoxia and hypercapnia, and whether hypersomnolence improves with more prolonged oxygen administration. In a single-blinded, nonrandomized trial, we compared the effects of 1 month of oxygen (4 L/min by nasal cannula) with room air (4 L/min by nasal cannula) placebo during sleep in 7 men and 1 woman with obstructive sleep apnea. During non-REM sleep, acute oxygen administration elevated the average low oxy-hemoglobin saturation during apneic events and decreased apnea frequency. These acute effects persisted during chronic oxygen administration but reverted to the preoxygen effects immediately upon discontinuing oxygen. One month of oxygen did not affect the waking ventilatory response to hypoxia or hypercapnia; however, waking PaCO2 increased from 40 +/- 1 mm Hg (mean +/- SE) after placebo to 43 +/- 1 mm Hg after oxygen (p less than 0.01). Neither subjective nor objective hypersomnolence consistently improved after 1 month of oxygen administration. We conclude that: first, oxygen has no effect upon apnea frequency beyond the period of administration, and the reduction of apnea frequency is not correlated with an increased sensitivity to chemical ventilatory stimuli. The reduced apnea frequency may be related to an increased PaCO2 stimulating ventilation during sleep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096179 TI - Enhanced IgE-dependent basophil histamine release and airway reactivity in asthma. AB - IgE-dependent basophil histamine release does not necessarily correlate with the amount of cell-bound IgE, thus it has been suggested that basophil "releasability" is an important, but yet undefined, factor in this secretory process. Because mast cell, and possibly basophilic leukocyte, mediator release contributes to airway reactivity, any enhancement of this secretory process would favor asthma provocation. To evaluate IgE-dependent basophil histamine releasability in asthma, suspensions of leukocytes were isolated from patients with an allergic and nonallergic component to their airway disease and stimulated with concanavalin A (Con A) (0.03 to 10.0 micrograms/ml) and anti-IgE (10 to 1,000 ng/ml). Basophil histamine release to Con A and anti-IgE was significantly greater in both allergic and nonallergic asthmatic patients when compared with normal subjects. In contrast, basophil histamine release to the calcium ionophore A23187 was similar in leukocytes from normal subjects and asthmatic patients, suggesting the observed abnormality in secretion may be limited to an IgE dependent process. To further determine if basophil histamine releasability in asthma correlated to measures of airway reactivity, bronchial provocation with histamine was performed. An inverse correlation was found between the provocative dose of inhaled histamine required to produce a 20% decrease, PD20, in the FEV1 and the leukocyte histamine release to Con A (p less than 0.05) and anti-IgE (p less than 0.05). Thus, we have new evidence that enhanced IgE-dependent release of leukocyte histamine correlates with airway reactivity in asthma. The mechanism of basophil releasability and its relationship to the pathogenesis of airway reactivity in asthma have yet to be established. PMID- 3096180 TI - Intraesophageal perfusion of acid increases the bronchomotor response to methacholine and to isocapnic hyperventilation in asthmatic subjects. AB - Gastroesophageal reflux (GER) has been shown to be more frequent in people with asthma, but the mechanism by which it might aggravate asthmatic symptoms remains unclear. We compared the effects on maximal expiratory flow at 50% of VC (MEF50) of esophageal perfusion of hydrochloric acid (HCl) and of normal saline (NaCl) in 12 asthmatic subjects chosen at random. In all subjects, HCl perfusion did not change MEF50 but potentiated the bronchoconstriction induced by isocapnic hyperventilation of dry air (maximal decrease in MEF50 = 44 +/- 7% with HCl versus 22 +/- 5% with NaCl; p less than 0.001) or methacholine (provocative dose producing a 20% decrease in FEV1 = 349 +/- 99 micrograms with HCl versus 496 +/- 119 micrograms with NaCl; p less than 0.01). Seven of the asthmatic subjects were found to have GER on esophageal pH monitoring. In these subjects, HCl alone decreased MEF50 slightly but significantly (-17.5 +/- 5.5%; p less than 0.05), possibly reflecting the higher degree of basal bronchial hyperreactivity observed in this group. Thus, perfusion of acid into the distal esophagus caused slight but significant bronchoconstriction in asthmatic subjects with GER and increased the bronchoconstriction produced by isocapnic hyperventilation and by methacholine in asthmatic subjects without regard for the presence of GER. PMID- 3096181 TI - Bicarbonate therapy in severe diabetic ketoacidosis. AB - Twenty-one adult patients with severe diabetic ketoacidosis entered a randomized prospective protocol in which variable doses of sodium bicarbonate, based on initial arterial pH (6.9 to 7.14), were administered to 10 patients (treatment group) and were withheld from 11 patients (control group). During treatment, there were no significant differences in the rate of decline of glucose or ketone levels or in the rate of increase in pH or bicarbonate levels in the blood or cerebrospinal fluid in either group. Similarly, there were no significant differences in the time required for the plasma glucose level to reach 250 mg/dL, blood pH to reach 7.3, or bicarbonate level to reach 15 meq/L. We conclude that in severe diabetic ketoacidosis (arterial pH 6.9 to 7.14), the administration of bicarbonate does not affect recovery outcome variables as compared with those in a control group. PMID- 3096182 TI - Long-term administration of gonadotropin-releasing hormone in men with idiopathic hypogonadotropic hypogonadism. A model for studies of the hormone's physiologic effects. AB - The effect of long-term administration of gonadotropin-releasing hormone (GnRH) for induction and maintenance of sexual maturation was characterized in 23 men with idiopathic hypogonadotropic hypogonadism. Twenty-two men achieved normal adult male serum testosterone concentrations (575 +/- 33 ng/dL; p less than 0.0001 compared with the baseline mean of 61 +/- 6 ng/dL) that were sustained in 21 men for up to 36 months with bolus doses of GnRH varying from 25 to 300 ng/kg body weight administered every 2 hours. Pulsatile luteinizing hormone (LH) secretion occurred in all 23 men, with mean levels of LH (14.7 +/- 1.3 mlU/mL) and follicle-stimulating hormone (11.3 +/- 1.3 mlU/mL) within or above the normal range for adult men. Mature sperm were observed in the ejaculates of 20 men, with counts ranging from less than 1 X 10(6) to 96 X 10(6)/mL. Increasing responsiveness of the pituitary-gonadal axis to GnRH was shown in 6 men. Men with idiopathic hypogonadotropic hypogonadism present a useful model to study the onset and maintenance of reproductive function in men. PMID- 3096183 TI - Plasma 3,4-dihydroxyphenylalanine (dopa) and catecholamines in neuroblastoma or pheochromocytoma. PMID- 3096184 TI - [Long-term (6 years) course of a congenital nephrotic syndrome treated by constant rate enteral nutrition]. PMID- 3096185 TI - [Treatment of pyocyanic bacillus superinfections in children with cystic fibrosis using a new cephalosporin: ceftazidime]. PMID- 3096186 TI - Selection and characterization of a Listeria monocytogenes vaccinal strain of reduced virulence for mice. AB - In an attempt to reproduce resistance to Listeria monocytogenes induced by primo infection, a vaccinal strain of low virulence capable of affording a good immunity was looked for. After a double mutation in regard to streptomycin, i.e. dependence then reversion to independence, nine strains were obtained from a Listeria monocytogenes field strain of low virulence. In addition, five of these reverse strains were made resistant to erythromycin. Measure of virulence of the resulting 14 strains was performed on mice by spleen counts three days after subcutaneous inoculation of 10(5) bacteria. A general decrease of virulence after the mutations was observed. Immunogenicity was estimated by spleen counts, three days after a challenge with parent strain on mice vaccinated one month previously with 10(6) organisms of each strain. A strain, resistant to erythromycin, was selected as potential vaccine, as having good immunogenicity, sufficiently reduced virulence, good growth ability and evident marker. This strain was shown resistant to 16 micrograms/ml of streptomycin and to 1000 micrograms/ml of erythromycin when respective values for parent strain were 4 micrograms/ml and 0.25 microgram/ml. Its metabolic activity in regard to glucids did not differ from that of parent strain but requirements in aminoacids increased at each step of the mutations leading from parent to selected strain. These characters were recognized as stable after two independent series of 10 passages on mice. PMID- 3096187 TI - Vaccination against Listeria infection in mice with a mutant strain of reduced virulence. AB - Killed Listeria monocytogenes (L.m.) or living Listeria innocua, being unable to afford noticeable immunity against L.m. challenge in mice, the efficacy of a living strain of L.m. of reduced virulence was studied. This strain was obtained from a field strain of low virulence by successive mutations for streptomycin dependence, reversion to independence and resistance to erythromycin. Its protective immunity was checked in mice against IV, SC and intra-gastric challenges. Vaccinated mice were protected against a IV challenge, lethal for controls, and they were rid of infection in a much shorter time than controls after SC or intra-gastric challenges. They were also protected against abortion when the challenge was done by SC, but not by IV route. The level of immunity was shown to be dose-dependent. Appearing very early after vaccination, immunity remained stable for at least four months, then decreased slowly afterwards, but could be restored and even enhanced by a recall. The protection was equally effective against L.m. serovars 1 or 4 challenges. PMID- 3096188 TI - [Anti-Brucella immunity transferred by immune serum and that transferred by splenic lymphocytes cannot be added]. AB - Immune serum and spleen cells from mice vaccinated with a cell-wall fraction (PG) from Brucella were previously shown to transfer a good protection to mice against a virulent Brucella challenge. This protection estimated by spleen and liver time course infection was similar to that afforded by vaccination. In present experiments, DBA/2 mice were first transferred with either immune serum from infected mice, splenic cells from mice intravenously vaccinated with PG fraction 28 days previously, or both immune serum and splenic cells. In this case, the serum was either injected before the challenge, as were the splenic cells, or 2 days after it in order to reduce the lowering effect of the serum on level of initial colonization of the spleen. The transferred mice were then intravenously challenged with the virulent strain B. abortus 544 and liver and spleen counts were performed on groups of five mice weekly up to six weeks. Immune serum and splenic cells from vaccinated mice were again shown to strongly reduce the time course of splenic infection. However addition of both effects was observed for a short time only two and three weeks post-challenge and only when the serum was injected after the challenge. In contrast, no additive or even an antagonistic effect was observed after the 21st day. Liver infection was not notably modified by both immune serum or splenic cells (except increment of initial colonisation by serum) until the 21st day when both helped reduce the course of infection. However again no additive effect was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096189 TI - [Aerobic bacterial flora of the nasal cavity of rabbits]. AB - On the basis of bacteriological examinations carried out in April 1984 on 60 intranasal swabs, aerobic respiratory microbes were studied in rabbits. Differences in flora between animals with and without respiratory diseases were studied. Fourteen bacterial species were identified with no difference due to the pathological status. They were: Bordetella bronchiseptica, Staphylococcus epidermidis, Streptococcus faecalis, Pasteurella multocida, Staphylococcus aureus, Bacillus sp., Branhamella catarrhalis, Micrococcus sp., Enterobacter agglomerans, Proteus mirabilis, Pseudomonas paucimobilis, Pseudomonas diminuta, Alcaligenes faecalis and Escherichia coli. However, young weaned rabbits were more often Pasteurella carriers than adult females in maternity. The usefulness of performing only Pasteurella and Bordetella cultures in rabbits is questionable as is use of vaccines in order to prevent bacterial respiratory syndrome. It is emphasised that myxomatosis should be pursued in the investigation of respiratory infections in rabbit. PMID- 3096190 TI - [Comparative study of the analgesic value of injectable lysine acetylsalicylate and noramidopyrine after orthopedic surgery]. PMID- 3096191 TI - Factor VIII procoagulant antigen levels in normal pregnancy and preeclampsia. AB - It has been suggested that the basis for the marked discordance in factor VIII parameters in preeclampsia is the result of proteolysis of the factor VIII procoagulant component (VIII:C) owing to activation of the coagulation system. To investigate this further, levels were compared of factor VIII:C and VIII:C (Ag), the immunologic equivalent of the procoagulant activity, in a series of preeclamptic patients and patients with uncomplicated pregnancies. No significant difference in the mean (+/- SD) level of factor VIII:C or VIII:C (Ag) could be detected between these groups. Our results do not support proteolysis of factor VIII:C as a mechanism to account for the discordant levels of the factor VIII parameters in preeclampsia. PMID- 3096192 TI - Natural history of Rickettsia rickettsii. PMID- 3096193 TI - The autotrophic pathway of acetate synthesis in acetogenic bacteria. PMID- 3096194 TI - Organization of the genes for nitrogen fixation in photosynthetic bacteria and cyanobacteria. PMID- 3096195 TI - Aryl-fluoroquinolone derivatives A-56619 (difloxacin) and A-56620 inhibit mitogen induced human mononuclear cell proliferation. AB - Aryl-fluoroquinolone derivatives A-56619 (difloxacin) and A-56620 were found to inhibit human peripheral blood mononuclear cell (MNC) proliferation (measured by [3H]thymidine uptake) that was induced by concanavalin A or monoclonal antibody OKT3. These antimicrobial agents exert their maximum suppressive effect when added within the first 24 h after the onset of culture with concanavalin A. No increase in the concentration of mitogen or the duration of incubation of MNC cultures reversed this inhibitory effect, but the removal of the drug from cultures reversed the suppression of DNA synthesis. A-56619 appeared not to interfere with the triggering of MNC activation by mitogen because it did not inhibit mitogen-induced increase in protein synthesis (measured by [3H]leucine incorporation), interleukin-2 receptor expression (measured by the binding of fluorescein-conjugated monoclonal antibody against interleukin-2 receptor), and cell volume. These findings are considered in terms of possible interference of aryl-fluoroquinolones with mammalian topoisomerase and DNA polymerases. PMID- 3096196 TI - Evidence for multiple forms of type I chromosomal beta-lactamase in Pseudomonas aeruginosa. AB - The multiple stages of derepression of the type I chromosomal beta-lactamase in Pseudomonas aeruginosa were examined. Mutants partially and fully derepressed for beta-lactamase were selected from a wild-type clinical isolate. An analysis of the beta-lactamase produced by these mutants and the induced wild type revealed significant differences in the products of derepression at each stage. Beta lactamase produced by the fully derepressed mutant showed a lower affinity (Km, 0.113 mM) for cephalothin than that produced by the partially derepressed mutant (Km, 0.049 mM). However, due to a very large Vmax, the former possessed a much greater hydrolytic efficiency. Differences in substrate profile were also noted. Only beta-lactamase from the fully derepressed mutant hydrolyzed cefamandole, cefoperazone, and cefonicid. The partially derepressed mutant possessed a single beta-lactamase band with a pI of 8.4. The fully derepressed mutant possessed this band and an additional major band with a pI of 7.5. Induction of the wild type with cefoxitin produced both bands. The changes in physiologic parameters of the enzymes produced in the different stages of derepression suggest a complex system for beta-lactamase expression in P. aeruginosa. This may involve at least two distinct structural regions, each of which is under control of the same repressor. PMID- 3096197 TI - Norfloxacin in the therapy of uncomplicated gonorrhea. AB - In an open study, 70 patients with uncomplicated anogenital Neisseria gonorrhoeae infection were evaluated to determine the efficacy and safety of a single oral dose of norfloxacin (800 mg). Norfloxacin cured all 31 male urethral and 25 endocervical infections. All 63 isolates of N. gonorrhoeae tested were inhibited by 0.05 microgram of norfloxacin per ml. PMID- 3096198 TI - The capital budget. Developing a capital expenditure proposal. PMID- 3096199 TI - Enzymatic transformations of 3-chloroalanine into useful amino acids. AB - The investigation of the combination of enzymatic and chemical synthetic processes for the production of useful compounds has been carried out. This review focuses on the enzymatic transformation of chemically synthesized 3 chloroalanine into useful amino acids. PMID- 3096200 TI - Depletion of human lymphocytes from peripheral blood and bone marrow by affinity ligands conjugated to agarose-polyacrolein microsphere beads. AB - Protein-A or goat anti-mouse-Ig (GAMIg) covalently bound to agarose-polyacrolein microsphere beads (APAMB) were employed for the removal of T cells from human peripheral blood leukocytes (PBL) and bone marrow (BM). The cell suspensions were treated with a monoclonal anti-T cell antibody (Leu-1) or monoclonal antilymphocyte antibody (CAMPATH-1) and passed through the conjugated APAMB columns. Cell separation efficacy was determined by assaying the number and function of T cells in the final cell preparation in comparison with a sample of unseparated cells. The number of cells that form rosettes (E-RFC) with sheep red blood cells (SRBC) in a sample of PBL treated with anti-Leu-1 antibodies and subsequently passed once through GAMIg-conjugated APAMB dropped from a range of 41.5-86.0% to a range of 1.6-13.3%. The in vitro response to concanavalin-A (Con A) dropped to a range of 0.7-27.2% (GAMIg) and a range of 1.2-21.8% (protein-A column) of the response of untreated PBL. Treatment with CAMPATH-1 antibody and passage through a protein-A-conjugated APAMB reduced E-RFC from a range of 55.6 57.4% to a range of 3.2-3.9% and abolished the Con-A induced proliferative responsiveness to background levels. Treatment of BM cells with CAMPATH-1 and passage of the cells through either GAMIg or protein-A conjugated APAMB columns resulted in reduction of E-RFC from a range of 12.4-17.7% to a range of 0-1% and from a range of 17.7-19% to a range of 1.6-3.2%, respectively. Viability of BM precursors, determined by the CFU-GM assay in semisolid medium, was not affected by these cell separation procedures. The data suggest that protein-A or GAMIg conjugated APAMB columns may be a useful tool for separation of BM cell suspensions into specific cell subsets that can be defined by monoclonal antibodies. PMID- 3096201 TI - Biogenesis of some antibiotics in the presence of 2-chloroethylphosphonic acid. AB - 2-Chloroethylphosphonic acid (CEPA) affected both the growth of and antibiotic production in Streptomyces aureofaciens, S. griseus, S. antibioticus, and Penicillium citrinum. Streptomyces strains seemed to be more sensitive to the presence of CEPA in the medium than did the fungus. A decrease in both growth and antibiotic production was observed with a concomitant increase in the concentration of the ethylene-releasing compound in the medium. Higher concentrations of CEPA completely inhibited the growth of the above microorganisms. PMID- 3096203 TI - Selective partitioning of conidia of some Penicillium and Aspergillus species in aqueous two-phase systems. AB - Conidia of Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Penicillium brevi-compactum, Penicillium frequentans, Penicillium spinulosum, and Penicillium verrucosum var. cyclopium were subjected to partition at varying pH values in an aqueous two-phase system containing charged polyethylene glycol. In the system, the partition behavior of the conidia of the Penicillium species varied when the pH was raised, while the conidia of the Aspergillus species seemed unaffected. P. brevi-compactum was separated from P. verrucosum var. cyclopium after only 10 transfers when subjected to stepwise partitioning. In the same way, 10 transfers were needed to separate P. verrucosum var. cyclopium from a mixture of conidia of three Aspergillus species. The partition behavior was influenced by the culture media used. PMID- 3096202 TI - Method for flow cytometric detection of Listeria monocytogenes in milk. AB - This report describes a method for the detection of Listeria monocytogenes in raw milk by flow cytometric analysis of fluorescently labeled bacterial populations. The use of immunofluorescence in combination with measures of DNA content by propidium iodide labeling and size by light scattering enabled specific identification of L. monocytogenes from Streptococcus faecalis, Streptococcus agalactiae, Streptococcus uberis, Staphylococcus epidermidis, and Staphylococcus hyicus. Additional specific resolution of L. monocytogenes populations was achieved through selective enrichment of raw milk in Listeria enrichment broth. These procedures should permit the rapid screening of milk and other food samples for L. monocytogenes and eliminate many of the short-comings associated with conventional fluorescent-antibody procedures. PMID- 3096204 TI - Residual effect of storage in an elevated carbon dioxide atmosphere on the microbial flora of rock cod (Sebastes spp.). AB - A residual inhibitory effect on microbial growth due to modified-atmosphere (MA) storage (MA, 80% CO2-20% air) was demonstrated for rock cod fillets stored in MA and transferred to air at 4 degrees C. Results of measurements of CO2 concentrations of the fillets suggested that the residual effect after transfer from MA to air was not due to retention of CO2 at the surface of the fillets but was probably due to the microbial ecology of the system. Lactobacillus spp. and tan Alteromonas spp. (TAN) predominated after 7 and 14 days of storage in MA. During storage in MA, Pseudomonas spp. were inhibited or killed. Following transfer from MA to air, the percentage of the total flora represented by Lactobacillus spp. and TAN bacteria decreased, and 6 days after transfer Pseudomonas spp. were again dominant. PMID- 3096205 TI - Overproduction from a cellulase gene with a high guanosine-plus-cytosine content in Escherichia coli. AB - A recombinant exoglucanase was expressed in Escherichia coli to a level that exceeded 20% of total cellular protein. To obtain this level of overproduction, the exoglucanase gene coding sequence was fused to a synthetic ribosome-binding site, an initiating ATG, and placed under the control of the leftward promoter of bacteriophage lambda contained on the runaway replication plasmid vector pCP3 (E. Remaut, H. Tsao, and W. Fiers, Gene 22:103-113, 1983). With the exception of an inserted asparagine adjacent to the initiating ATG, the highly expressed exoglucanase is identical to the native exoglucanase. The overproduced exoglucanase can be isolated easily in an enriched form as insoluble aggregates, and exoglucanase activity can be recovered by solubilization of the aggregates in 6 M urea or 5 M guanidine hydrochloride. Since the codon usage of the exoglucanase gene is so markedly different from that of E. coli genes, the overproduction of the exoglucanase in E. coli indicates that codon usage may not be a major barrier to heterospecific gene expression in this organism. PMID- 3096207 TI - Radiation resistance of lactobacilli isolated from radurized meat relative to growth and environment. AB - Of 113 lactobacilli isolated from radurized (5 kGy) minced meat, 7 Lactobacillus sake strains, 1 L. curvatus strain, and 1 L. farciminis strain were used for radiation resistance studies in a semisynthetic substrate (i.e., modified MRS broth). Five reference Lactobacillus spp., one Staphylococcus aureus strain, and one Salmonella typhimurium strain were used for comparative purposes. All L. sake isolates exhibited the phenomenon of being more resistant to gamma-irradiation in the exponential (log) phase than in the stationary phase of their growth cycles by a factor of 28%. Four references strains also exhibited this phenomenon, with L. sake (DSM 20017) showing a 68% increase in resistance in the log phase over the stationary phase. This phenomenon was not common to all bacteria tested and is not common to all strains with high radiation resistance. Four L. sake isolates and three reference strains were used in radiation sensitivity testing in a natural food system (i.e., meat). The bacteria were irradiated in minced meat and packaged under four different conditions (air, vacuum, CO2, and N2). Organisms exhibited the highest death rate (lowest D10 values [doses required to reduce the logarithm of the bacterial population by 1] ) under CO2 packaging conditions, but resistance to irradiation was increased under N2. The D10 values of the isolates were generally greater than those of the reference strains. The D10 values were also higher (approximately two times) in meat than in semisynthetic growth medium. PMID- 3096206 TI - Automation of microbial enumeration: development of a disposable hydrophobic grid membrane filter unit. AB - A disposable filter unit containing a hydrophobic grid-membrane filter (HGMF) was developed. The unit is liquid tight to serve as a specimen transport container and, by removal of the funnel extender (175- or 300-ml capacity), the unit becomes less than the height of two stacked petri plates to save space during in situ incubation. The polyethylene mesh which supports the HGMF facilitates rinse removal of any substance(s) that would interfere with microbial growth. The correlations between a pour plate, a conventional square HGMF, and a disposable filter unit on microbial enumeration were examined. Characteristics (e.g., clumping, spreading, etc.) of some microorganisms limit the linear counting range to less than 1,000 CFU per filter. PMID- 3096208 TI - Presence of Aspergillus flavus in developing cotton bolls and its relation to contamination of mature seeds. AB - Aspergillus flavus spores were dusted onto the involucral nectaries of cotton flowers. The fungus was present in 20 to 58% of the immature bolls harvested 25 or 35 days after anthesis. Among similarly inoculated bolls fully matured either in the field or under sterile conditions at ambient temperatures after excision from the plants, only 3 to 14% contained A. flavus in the seeds. There was no significant difference in the numbers of contaminated bolls between the excised and field-matured treatments. It is concluded that A. flavus is present in developing cotton bolls before dehiscence, but its presence does not ensure infection of mature seeds, and that excision does not reduce A. flavus contamination if the bolls are maintained at ambient temperatures. PMID- 3096209 TI - Highly unsaturated phospholipid molecular species of rat erythrocyte membranes: selective incorporation of arachidonic acid into phosphoglycerides containing polyunsaturation in both acyl chains. AB - This study describes for the first time the complete molecular species composition and turnover of [3H]arachidonic acid in various glycerophospholipid classes of rat erythrocytes, a model system that has been extensively used to investigate numerous membrane phenomena. Quantitative analysis of the individual molecular species of the choline, ethanolamine, serine, and inositol glycerophospholipid classes was possible by preparing their diradylglycerobenzoate derivatives that can be quantitated by on-line uv detection in conjunction with high-performance liquid chromatography; turnover of the molecular species containing arachidonate was evaluated in erythrocytes labeled with [3H]arachidonic acid. A unique observation was the significant amounts of 22:6-20:4, 20:4-20:4, and 18:2-20:4 species observed in the diacyl fractions of phosphatidylethanolamine and phosphatidylserine. Moreover, the analysis of the specific radioactivities of individual phospholipid species from erythrocytes incubated with [3H]arachidonic acid demonstrated a selective incorporation of arachidonic acid into the most highly unsaturated molecular species in all of the phospholipid classes examined. Although the 22:6-20:4, 20:4 20:4, and 18:2-20:4 species represented only 4.5% of the total mass of the diacyl phosphoglycerides, these species accounted for a major portion (37%) of the arachidonic acid incorporated into the phospholipids. These results demonstrate the existence of unique populations of phospholipid molecules in rat erythrocytes with a high degree of unsaturation that exhibit a very rapid metabolic turnover rate. PMID- 3096210 TI - Phosphorylation of rabbit skeletal muscle glycogen synthase by casein kinase 1: evidence of phosphorylation sites specific for casein kinase 1. AB - Casein kinase 1 phosphorylated rabbit skeletal muscle glycogen synthase at both seryl and threonyl residues. With glycogen synthase phosphorylated up to 7.5 mol phosphate/mol subunit, about 26% of the phosphate was present in the N-terminal cyanogen bromide fragment (CB1) and 74% in the C-terminal fragment (CB2). Both fragments contained phosphothreonine (11 to 14%) in addition to phosphoserine. When 32P-labeled glycogen synthase was totally digested with trypsin and chromatographed on reverse-phase high-performance liquid chromatography, seven phosphopeptides were observed. Peptide I eluted in the vicinity of the peptide containing site 1a, peptide II coincided with sites 4 + 5, peptides III and IV eluted in the region corresponding to sites 3a + 3b + 3c, peptide V appeared slightly after the peptide containing site 1b and peptide VII behaved as the peptide containing site 2, whereas peptide VI did not coincide with any of the known phosphopeptides. Limited trypsinization prior to analysis by HPLC led to the disappearance of peaks V and VI without altering peaks I to IV and VII. Only peaks I and VII remained when limited chymotrypsinization was performed prior to HPLC analysis. Chromatography on HPLC of the fragments derived from complete trypsinization of CB2 showed the presence of peaks II to VI. Phosphoamino acid analysis of the different peptides demonstrated the presence of quantitative amounts of phosphothreonine in peptides V, VI, and VII. These results indicate that multiple phosphorylation sites for casein kinase 1 must exist in both the N terminal and C-terminal regions of glycogen synthase, some of which would only be labeled by casein kinase 1. PMID- 3096211 TI - Purification and characterization of NADH dehydrogenase complex from Paracoccus denitrificans. AB - An NADH dehydrogenase complex was isolated from the plasma membranes of aerobically grown Paracoccus denitrificans cells by extraction with NaBr and purification on an NAD-agarose column. The NADH-ubiquinone-1 reductase activity of the isolated NADH dehydrogenase complex was about 10 times higher than that of the NaBr extract. The preparation was composed of 10 (6 major and 4 minor) unlike polypeptides, and lacked identifiable components and activities characteristic of other enzyme complexes of the oxidative phosphorylation system. The purified enzyme contained noncovalently bound FMN, nonheme iron, and acid-labile sulfide. The ratio of FMN to nonheme iron to acid-labile sulfide was 1:13 approximately 14:11 approximately 12, suggestive of the presence of multiple iron-sulfur clusters. The isolated NADH dehydrogenase complex cross-reacted with antisera to beef heart mitochondrial complex I and protein fraction derived therefrom, indicating the presence in the Paracoccus enzyme of antigenic sites similar to those in the intact complex I and its iron-sulfur protein and possibly hydrophobic protein fractions. PMID- 3096212 TI - Purification and characterization of a glycogen phosphorylase analog missing the amino-terminal segment. AB - A glycogen phosphorylase analog missing only the amino-terminal 16 to 18 residues, which include the phosphorylation site, was produced by subtilisin Carlsberg cleavage of phosphorylase b in the presence of caffeine. The analog, named phosphorylase b's, was purified, and its enzymatic properties were compared with those of phosphorylase b. The KM's for glucose 1-phosphate are similar, but phosphorylase b's has a VM 43% higher than that of phosphorylase b. Also, phosphorylase b's is less sensitive to inhibition by glucose 6-phosphate and stimulation by sodium fluoride than is phosphorylase b. The subunit interactions in the two enzyme forms were also compared. The monomer-monomer interactions in phosphorylase b's are weaker than in phosphorylase b, as evidenced by a faster rate of resolution of the coenzyme, pyridoxal phosphate, from phosphorylase b's. The dimer-dimer interactions are also weaker in phosphorylase b's than in phosphorylase b, because phosphorylase b's does not form tetramers or crystals as readily as does phosphorylase b. Because removal of the amino-terminal segment changes the properties of the enzyme, this segment must be interacting with other parts of the protein. This statement conflicts with previous interpretation of X ray crystallographic data that suggest that the amino-terminal region of phosphorylase b is freely mobile. Possible explanations for this contradiction are discussed. PMID- 3096214 TI - [Postoperative management of total pancreatectomy]. AB - Sixteen patients given total pancreatectomy were experienced, and the essential points of postoperative management were reported. The morbid states after total pancreatectomy consist of: a deficiency of pancreatic endocrine function, a deficiency of pancreatic exocrine function, loss of the duodenum and upper jejunum, the influence of partial or total gastrectomy, and the influence of dissection around the superior mesenteric artery. These states influence each other and become more complicated. The management period is divided into five parts as follows; a period of intravenous nutrition, the early half; water replacement period, the late half; hyperalimentation period, a period of intravenous and enteral nutrition, a period of enteral, intravenous and oral nutrition, a period of oral and enteral nutrition, and a period of oral nutrition. In each period, a special form of management is needed. The essential points of long-term management are as follows: The use of suitable doses of pancreatic enzyme and antidiarrheal agents for the cure of severe maldigestion and malabsorption. Also, intermittent IVH or elemental diet are effective for recovery from deteriorative malnutrition. For the prevention of hypoglycemic attack, training of the patients and the maintainance of good nutrition are important. These patients have a high incidence of infection, and so speedy treatment must be given if this occurs. Fatty liver must be treated by intermittent IVH or elemental diet. As total pancreatectomy imposes a severe burden on the patient, including self-injection of insulin, the indications of this operation must be decided carefully giving due consideration to its radicality. PMID- 3096213 TI - Activation of hepatocyte glycogen synthase by metabolic inhibitors. AB - Incubation of isolated rat hepatocytes with metabolic inhibitors causes an increase in the -glucose 6-P/+glucose 6-P activity ratio of glycogen synthase after decreasing ATP and increasing AMP levels. Concomitantly, the activity of phosphorylase is increased six-fold by the same treatment. This activation of both enzymes remains after gel filtration of the hepatocyte extracts. Addition of metabolic inhibitors to cells pretreated with an inhibitor of AMP-deaminase results in an accumulation of AMP and, simultaneously, in a further increase in the activation state of glycogen synthase. The correlation coefficient between the intracellular concentration of AMP and glycogen synthase activity is r = 0.93. It is proposed that the covalent activation of glycogen synthase by metabolic inhibitors can be triggered by changes in the level of the intracellular concentrations of adenine nucleotides. PMID- 3096215 TI - [Synergistic effect of recombinant human interferon-beta and -gamma on human colon cancer transplanted into nude mice]. AB - The antitumor effect of recombinant human interferon-beta (r IFN-beta) and recombinant interferon-gamma (r IFN-gamma) was studied in vivo using a pulmonary metastatic model involving nude mouse human colon cancer xenografts. The results indicated that both r IFN-beta and r IFN-gamma had an inhibitory effect on pulmonary metastases. Furthermore, a combination of r IFN-beta and r IFN-gamma acted synergistically in the inhibition of pulmonary metastases. These results suggested that a combination of r IFN-beta and -gamma could be a most effective form of interferon therapy for cancer. PMID- 3096216 TI - [Induction of tumoricidal properties in human monocytes by synergism between interferon-gamma and liposome-entrapped muramyl tripeptide]. AB - Human blood monocytes from healthy volunteers, separated by centrifugal elutriation, were not cytotoxic to allogeneic A 375 melanoma cells. The monocytes were rendered tumoricidal by incubation for 24 h with natural interferon-alpha and beta or recombinant interferon-alpha A and alpha A/D (more than 100 U/ml) or with interferon-gamma (more than 1 U/ml). Liposome-MTP-PE at concentrations of more than 50 nmol/ml also induced tumoricidal activity of monocytes. When a combination of subthreshold concentrations of these IFNs and liposome-MTP-PE were added to monocyte cultures, IFN-alpha and beta acted additively in monocyte activation, while IFN-gamma acted synergistically. The synergism for monocyte activation required that monocytes be incubated first with IFN-gamma and then with liposome-MTP-PE. These findings suggest that the synergistic effect of IFN gamma and liposome-MTP-PE can decrease the necessary clinical doses of these agents for malignant diseases, and may have therapeutic availability in the treatment of metastatic cancer in humans. PMID- 3096218 TI - [Comparative clinical study of SF-SP therapy and SF-SP plus BH-AC therapy in gastrointestinal cancer. Tokyo Cancer Chemotherapy Cooperative Study Group]. AB - SF-SP which contains sustained release granules of tegafur has been reported to be effective for gastrointestinal and breast cancer. HB-AC, which is an anti leukemic agent, is known to have considerable activity against a variety of transplanted solid tumors in rats and mice. A comparative clinical study was therefore conducted by randomized controlled trial on the two different chemotherapies, involving as SF-SP group and as SF-SP plus BH-AC group. Among 58 patients, 42 were evaluable for response (SF-SP: 20/30, SF-SP plus BH-AC: 22/28). The partial response rate of SF-SP was 15.0% (3/20) and that of SF-SP plus BH-AC was 13.6% (3/22). The toxicity rates of SF-SP and SF-SP plus BH-AC were 33.3% (10/30) and 36.0% (9/25), respectively. These results indicated that the two therapies were similar in both response and toxicity rates. However, the response appeared faster in the case of SF-SP plus BH-AC therapy than in that of SF-SP therapy. PMID- 3096217 TI - [Combined effect of PT-050 (recombinant human TNF) and antitumor drugs on syngeneic murine tumors]. AB - The combined effect of PT-050 (recombinant human TNF) and various antitumor drugs was investigated using murine colon 26 adenocarcinoma, Meth A sarcoma and B16 melanoma transplanted into syngeneic mice. When colon 26- or Meth A- bearing mice were intravenously given PT-050 in combination with mitomycin C (MMC), doxorubicin (DXR), cis-platinum (CDDP), 5-fluorouracil (5-FU) or cyclophosphamide (CPA), a significant synergistic effect was observed, that is, both the inhibition rate of tumor growth and the cured ratio were increased significantly when compared with those given each drug alone. Similarly, an augmentation of the antitumor effect was also observed in B16-bearing mice by a combined treatment with PT-050 and these antitumor drugs. These results suggest that the combination chemotherapy of PT-050 with various antitumor drugs may be useful for cancer therapy. PMID- 3096219 TI - Alpha-heavy-chain disease with erythematous skin lesions. PMID- 3096220 TI - Normocholesterolemic xanthomatosis. PMID- 3096221 TI - Topical antibiotic treatment of impetigo with mupirocin. AB - Because the effectiveness of topical antimicrobials in the treatment of ecthyma, impetigo, and pyoderma is not well established, the US Food and Drug Administration has recently proposed guidelines for tests of topical antimicrobial efficacy in primary skin infections. The guidelines require both comparison with the agent's base and microbiologic documentation of efficacy. These guidelines were followed in this double-blind, eight-day evaluation of impetigo/ecthyma treated with mupirocin, a new agent that is only active topically. All cultures, before and after therapy, were taken using swabs dipped in neutralizing broth plus 10% fetal bovine serum to minimize antimicrobial "carry over" to the culture plate. Staphylococcus aureus, which was isolated from 94% of the patients before therapy, was eliminated in 88% of the mupirocin treated patients and 47% of the vehicle-treated patients. Group A beta-hemolytic streptococci were eliminated in 100% of the mupirocin-treated and 0% of the vehicle-treated patients. To our knowledge, this is the first topical antibacterial treatment for primary skin infections proved superior to its vehicle using the proposed US Food and Drug Administration guidelines. PMID- 3096222 TI - Why do so many small infants develop an inguinal hernia? AB - Prevalence and incidence of inguinal hernia in a representative sample of low birthweight survivors were determined by tracing children at 3 years of age. Prevalence was examined in relation to perinatal factors recorded in hospital case notes, using a logistic regression model to allow for confounding variables. Of the 1074 two year survivors, 995 (93%) were assessed. Seventeen per cent of 497 boys and 2% of 498 girls had a hernia by 3 years of age, a total cumulative prevalence of 9.2%: it was significantly increased by lower birth weight, male sex, neonatal intravenous feeding, and lack of respiratory disease. Neonatal illnesses were otherwise not associated with herniation, and most infants were well when they presented. Peak incidence was at the expected full term of gestation. Bilateral hernias were increasingly more common than unilateral hernias at lower gestational ages. It is proposed that causes of increased abdominal pressure in healthy neonates are important causes of herniation during a critical period of inguinal development. PMID- 3096223 TI - Pure red blood cell aplasia: response to intravenous immunoglobulins, a blocking antibody. PMID- 3096224 TI - [Free radical toxicity in coronary insufficiency]. AB - A number of experimental models have shown abnormally high concentrations of cytotoxic oxygen derived free radicals (FR), and decreased concentrations of protecting anti-oxidising enzymes during myocardial ischaemia. These FR react with the unsaturated lipids of the cell membrane, a phenomenon known as membrane lipidoperoxidation (MLP) to produce very cytotoxic endoperoxides. We studied an intermediary product of MLP, malondialdehyde (MDA) in 10 patients with a preinfarction syndrome (Group 1) and 8 patients in the acute phase of myocardial infarction (Group 2). Plasma MDA was measured on admission (P2) and 12th day (P3). There was a significant elevation of MDA in both groups at P1 and P2 (p less than 0.01) compared with results obtained in 15 normal control subjects of the same age. The MDA concentration on the 12th day in the infarct group was significantly lower (189 +/- 41 ng/ml, p less than 0.01) compared with the highest value observed either on admission or on the 5th day (peak MDA 258 +/- 62 ng/ml). The difference between MDA concentrations on the 12th day and peak MDA was less striking in Group 1. None of the patients in Group 2 had a recurrence of chest pain after the initial phase of infarction and the residuals MDA concentration (P3) was similar to control values (181 +/- 27 ng/ml). On the other hand, in the preinfarction syndrome group, 4 patients had persistent unstable angina on the 12th day and their MDA concentrations remained high (250 +/- 42 ng/ml). This was interpreted as reflecting continuing MLP in these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096226 TI - [Anatomical and hemodynamic evolution at midpoint follow-up with the assisted heart in heterotopic heart transplantation. Apropos of 21 cases]. AB - Between November 1978 and March 1985, 27 cardiac transplant operations were performed at the Arnault Tzanck Institute; Barnard's heterotopic method was used in 21 cases. In 16 cases, follow-up was prolonged to assess the effects on the assisted receiving heart. In the first postoperative hours the receiving heart is often more effective than the graft. There were no pathological consequences due to the two different rhythms. The increased pressures in the right cavities of the receiving heart decreased but sometimes this look several weeks. The volume of the left atrium decreased. Left ventricular contraction was unchanged in some cases but in others it improved significantly. This was accompanied by an average decrease of 20 mm in echocardiographic left ventricular end diastolic internal dimension. This technique of heterotopic assistance seems particularly suitable for advanced stages of cardiomyopathy with stage IV pulmonary hypertension. PMID- 3096225 TI - [Mechanisms determining sudden death. A cooperative study of 69 cases recorded using the Holter method]. AB - A cooperative study involving 23 centres enabled review of 69 cases of sudden death occurring less than one hour after onset of symptoms recorded by the Holter method and not related to recent, clinically documented myocardial infarction or to class IV cardiac failure. The 15 cases of asystole (22 p. cent) were observed in elderly patients (73.3 +/- 2.7 years) whose known ischaemic heart disease (12/15) was confirmed in 10 cases as the direct cause by the preceding acute ST changes. In 2 cases, death resulted from AV block presumed to be iatrogenic. The 13 episodes of torsades de point (19 p. cent) occurred mainly in younger women (58.8 +/- 6 years) without apparent cardiac disease (8 cases) and were provoked by a Group IA antiarrhythmic drug (7 cases) or by hypokalemia (3 cases). Apart from 1 case of congenital long QT syndrome, slowing of the sinus rhythm was observed (78.3 +/- 2.6 to 60.2 +/- 2.7 bpm, p less than 0.001) in the 3 hours preceding these episodes, and ventricular bigeminy with a long coupling interval was recorded in the lasts seconds before the torsades. The 41 (59 p. cent) cases of ventricular fibrillation (VF) were observed in men aged 64.9 +/- 2 years with coronary artery disease (39/41). However signs of acute ischaemia were only found in 5 cases. The VF was primary in 8 cases and secondary to ventricular tachycardia (VT in 33 cases). An acceleration of the cardiac rhythm (83.3 +/- 3.4 to 90 +/- 4.1 bpm, p less than 0.01) was recorded in the hour preceding VF and other arrhythmias were common: atrial tachycardia (4 cases), atrial extrasystoles (4 cases), a new type of ventricular extrasystoles (VES). The VF and VT were preceded by a long cycle in 17 cases. The first complex was different from previous VES in 10 cases and identical to the previous VES in 16 cases; in 4 cases this feature could not be identified and in 11 cases there were no premonitory VES. The coupling interval of the initial VES was shorter than that of the most premature preceding VES (368 +/- 13 ms vs 442 +/- 19 ms, p less than 0.001), especially in primary VF (335 +/- 9 ms, N = 8) compared to polymorphic VT (360 +/- 12 ms, N = 11) or monomorphic VT (384 +/- 18 ms N = 22).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096227 TI - [Midpoint follow-up results of aortic valve replacement with the Ionescu-Shiley pericardial bioprosthesis. Apropos of 109 patients]. AB - Between March 1980 and May 1985, 109 adults with an average age of 59 years underwent aortic valve replacement with a pericardial Ionescu-Shiley xenograft. Twenty six of the prostheses were of small size (N 19 and 21). In 20 patients, the operation was associated with another procedure (15 aorto coronary bypass grafts and 5 conservative mitral valve procedures). Before surgery, 73.4% of patients were in functional Stages III or IV, and 9.2% had permanent or paroxysmal atrial fibrillation. The average follow-up period was 24 months (4 to 59). The operative mortality was 5.5%. The 4 year actuarial survival rate was 86% with 82% good functional results. At the same date, 96.4% of patients had not developed endocarditis, 96% had not been reoperated and 93.8% had no prosthetic valve dysfunction. No cases of primary degeneration were observed but a diastolic murmur without any haemodynamic consequences was detected in 20% of patients at 4 years. Seventy four per cent of subjects were not anticoagulated at 1 year and 85% were without anticoagulants after one year. Only one haemorrhagic complication was noted (0.46% patient/years). There were no cases of occlusive thrombosis; the incidence of thromboembolism was 3.7% patient/years in aortic without mitral valve disease, irrespective of the cardiac rhythm and 2.7% patient/years in patients in sinus rhythm. In this subgroup, 88% had not had any thrombo-embolic complication despite the absence of anticoagulants at 4 years. An Indium III labelled platelet scan was positive in 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096228 TI - [Ultrasonic detection of arteriosclerosis of the main arterial trunks in the coronary patient]. AB - Ultrasonic investigations of the peripheral vessels (continuous Doppler with spectral analysis, echotomography) were performed to evaluate atherosclerosis of the main arteries (abdominal aorta, cervical arteries, lower limb arteries) in 50 coronary patients and 40 control subjects. In the main, our results support those of previously published series (epidemiological and autopsy studies): Atherosclerosis of the main arterial vessels is significantly more common (p less than 0.01) in coronary patients than in control subjects: carotid lesions: 70% (including 10% with severe stenosis) compared to 32% (no severe stenosis); aortic lesions: 50% (including 20% with severe stenosis) compared to 17.5% (7.5% severe stenosis); lower limb arteries: 58% (including 16% severe stenosis) compared to 12.5% (no severe stenosis). The difference of incidences of associations of atherosclerosed vessels between the two groups was significant (p less than 0.01): no peripheral vascular disease was detected in 57.5% of controls compared to only 12% of coronary patients; more than one territory diseased in 15% of controls compared to 58% of coronary patients. The severity of these lesions correlated with the presence of the three major cardiovascular risk factors which were studied (hypertension, smoking, hypercholesterolaemia) and was significantly higher (p less than 0.01) in coronary patients (38% had more than one major risk factor and only 10% had none) than in controls (47% had no risk factors and 6% had more than one). In addition, the preferential sites of atherosclerosis were also confirmed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096229 TI - [Acute native endocarditis. The results of surgical treatment]. AB - Between January 1978 and December 1984, 141 cases of acute native valve endocarditis were treated surgically in the Department of Thoracic and Cardiovascular Surgery of the Pitie Hospital. The diagnostic criteria of acute native valve endocarditis were the duration of treatment (antibiotic therapy for less than 40 days), the characteristic operative appearances of the lesions, and the results of anatomo-pathological examination of the excised valves. The infecting organism was not isolated in 35% of cases. The aortic valve was the commonest site of infection (65.2% with a high incidence of abscess of the aortic ring, irrespective of the causal organism. The operative mortality was 5.6%. This depended mainly on the preoperative haemodynamic status of the patient. The duration of antibiotic therapy prior to surgery did not seem to be relevant. The 3 years survival rate was 78%. The secondary reoperation rate was 7%. There was a higher incidence of secondary perivalvular regurgitation in patients who had previously had an abscess of the aortic ring. PMID- 3096230 TI - [Catheter ablation after the direct electrical recording of the bundle of Kent. Apropos of 3 cases]. AB - The success rate of catheter ablation, the latest therapeutic method in the treatment of cardiac arrhythmias, varies according to the precise indication. The best and most logical guarantee of its efficacy is the application of the electrical energy at an anatomical site essential to the arrhythmia. In preexcitation syndromes this site is without doubt the accessory pathway itself rather than its insertions, but this implies the recording of its activation. We recorded the electrical activation of a right sided Kent bundle in three consecutive cases to guide the therapeutic procedure (comparable to the recording of the H potential for his bundle ablation). All patients had paroxysmal atrial fibrillation (minimal RR interval: 175, 150 and 200 ms) and orthodromic reciprocating tachycardia. Two patients had had attacks of ventricular fibrillation. The sites of the Kent bundles were posteroseptal in 2 cases and anterolateral in 1 case. The recording of the electrical activation of the Kent bundle was validated by: the passage (induced or spontaneous) of a preexcited to a normal QRS coincident with the disappearance of the K potential; the exclusion of an atrial or ventricular origin of the electrical activation supposed to be the activation of the Kent bundle; electrical stimulation at the site of the recording of the K potential leading to prolongation of the stimulus-delta wave interval from 10 to 35 ms, with QRS morphology identical to the spontaneous complexes. All 3 patients were clinically cured by catheter ablation at the site of recording of the Kent bundle activation with follow-up periods ranging from 10 to 16 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096231 TI - [Unruptured aneurysms of the sinus of Valsalva disclosed by syncopal disorders of cardiac excitability. Apropos of 2 cases]. AB - Aneurysms of the sinus of Valsalva are rarely diagnosed before rupture into the cardiac cavities which usually leads to the appearance of a continuous murmur and cardiac failure. In the two cases described, the presenting symptom of the aneurysm was syncope due to cardiac hyperexcitability: ventricular tachycardia in the first and paroxysmal tachyarrhythmia in the second case. The presenting symptoms of unruptured aneurysms of the sinus of Valsalva were analysed. In general, they are: uncontinuous cardiac murmurs: either diastolic murmurs of aortic regurgitation, systolic murmurs of mitral or tricuspid regurgitation, or, as in our first case, of obstruction to right ventricular ejection; arrhythmias: the commonest are conduction defects, which can be syncopal; hyperexcitability (especially ventricular) seems to be very care. Echocardiography is a valuable tool for the diagnosis of sinus of Valsalva aneurysms. The appearances of unruptured aneurysms in our two patients are described. The presence of syncopal cardiac hyperexcitability, possibly associated with one of the preceding auscultatory abnormalities is an indication for echocardiography which may lead to the diagnosis of this condition. PMID- 3096232 TI - [Pheochromocytoma of the organ of Zuckerkandl]. AB - The authors report the case of a pheochromocytoma of the organ of Zuckerkandl in a 46 year old man. The clinical presentation was severe paroxysmal hypertension; the tumour was located by arteriography, CT scanning, and by scintigraphy with iodine labelled benzylguanidine. The blood pressure returned to normal after surgery. The embryological, anatomical and physiological features of the organ of Zuckerkandl are reviewed: the authors discuss briefly the modern methods of diagnosis and localisation of the tumour. PMID- 3096233 TI - [Treatment of torsade des pointes by intravenous magnesium]. AB - A 72 year old woman was admitted with decompensation of a hypertensive cardiopathy and treated with diuretics. She developed recurrent syncopal torsades de pointes during the 24th hour which were reduced by a bolus intravenous injection of 3 g of magnesium sulphate (Mg SO4). There was a recurrence 30 minutes later which regressed after a second injection of 3 g of Mg SO4. A continuous intravenous infusion of 18 g/day of Mg SO4 prevented further recurrences of the arrhythmia. Biochemical analysis showed intra and extracellular magnesium deficiency at the time of the torsades de pointes but the intracellular potassium was normal. The QT interval was prolonged but this parameter did not change after the bolus of Mg SO4. It returned to normal progressively afterwards. The clinical course was uncomplicated with no recurrences. Metabolic correction was obtained in 3 days. This observation raises the question of the mechanisms relating diuretic therapy, magnesium and torsades de pointes. PMID- 3096234 TI - [Spontaneous incomplete rupture of the supra-sigmoidal aorta presenting as aortic insufficiency. Apropos of an emergency surgical case]. AB - We report a case of spontaneous incomplete rupture of the first segment of the ascending aorta presenting as aortic incompetence and acute tamponade confirmed by preoperative angiography in a 57 year old hypertensive woman. This patient underwent emergency conservative surgery with good results at 8 months' follow up. This rare pathology occurs in the same terrain as dissection of the aorta. The diagnosis should be suspected not only when chest pain and/or aortic incompetence are associated or not with acute tamponade, contrasting with a normal electrocardiogram, but also in atypical presentations which necessitate angiography in multiple incidences in order not to miss the diagnostic signs which are often invisible in the standard projections. When there are no complications, this condition may pass undiagnosed. However, in most cases, it leads to acute tamponade due to intrapericardial rupture or to an aortic aneurysm or aortic incompetence. The latter complications are usually associated with severe regurgitation requiring surgical correction, which in some cases may be conservative. PMID- 3096235 TI - [Cardiac contusion with dissecting hematoma of the apex of the heart and interventricular communication]. AB - The authors report the case of a post-traumatic ventricular septal defect diagnosed after the detection of a systolic murmur in a 39 year old man, 18 months after a car accident. Two-dimensional echocardiography and angioscintigraphy showed an abnormal cavity at the apex of the heart. At cardiac catheterisation there was a moderate left-to-right ventricular shunt through this cavity. There were no traumatic or atheromatous lesions of the coronary arteries. The operative appearances were of stunned myocardium which had caused a dissecting haematoma of the cardiac apex which ruptured into both ventricular cavities. The lesions were corrected surgically and the systolic murmur disappeared. PMID- 3096236 TI - [Compression of the right pulmonary artery by a dissecting aneurysm of the ascending aorta. Apropos of a case occurring long after aortic valve replacement]. AB - The authors report the case of a dissecting aneurysm of the ascending aorta compressing the right pulmonary artery in a 62 year old man, 6 years after aortic valve replacement. The clinical presentation was that of pulmonary embolism. The diagnosis was confirmed by angiopneumography and CT scanning. The ascending aorta was successfully replaced with a Dacron prosthesis. One other case was found in a review of the literature. After discussing the predisposing factors of aortic dissection during cardiac surgery, the authors underline the diagnostic value of CT scanning in cases of suspected aneurysms of the thoracic aorta. PMID- 3096237 TI - [Electrophysiologic effects of a spironolactone-altizide combination on the isolated rat heart]. AB - The association of spironolactone and altizide is effective in the treatment of some forms of resistant oedemas. Our aim was to determine whether the renal effects of this association were associated with abnormal cardiac cellular electrophysiological changes. Isolated rat hearts perfused by the retrograde aortic approach and paced at 200 beats per minute were studied. Cardiac cellular activation was measured by floating microelectrodes in the subepicardial layers of the left ventricle. The following parameters were analysed: the duration of the action potential at 25% and 75% of repolarisation (DAP25 and DAP75), the timing and amplitude of the point of rupture of the action potential (T.PR and A.PR), the amplitude of the action potential at 40 ms (A.40). A simultaneous variation of 3 of these parameters was considered to be a significant change. The animals were given an intraperitoneal injection of either 2.5 mg/kg or 10 mg/kg of spironolactone, 0.25 mg/kg or 1 mg/kg of altizide or any association of these two drugs at the given dosages. Spironolactone alone at these dosages did not cause any change in the electrical activation of the rat ventricular myocardial cell. On the other hand, 1 mg/kg of altizide produced a significant increase in the duration of the ventricular action potential at zero potential (DAP25) and during the plateau phase (T.PR and A.40). These changes, which could be related to the potassium metabolism, were abolished when altizide was associated with spironolactone. This is probably a similar effect to that of the prevention of hypokalaemia and low intracellular potassium concentrations when associating a potassium sparing drug with hypokalaemic diuretics. PMID- 3096238 TI - [Percutaneous electric interruption of normal auriculoventricular conduction. Analysis of French cases]. AB - Since 1982, 85 patients (aged 18 to 81 years) with supraventricular arrhythmias resistant to an average of 3.8 +/- 1.2 classes of antiarrhythmic drugs, 53 of whom had underlying cardiac disease (62.3%), underwent attempted catheter ablation of the normal AV conduction pathway in 8 different French centers. The indication was atrial fibrillation and flutter in 51 cases (60%) and intranodal reentry in 16 cases (18.8%). An average of 2.5 +/- 2.3 electrical shocks of 130 to 400 joules delivered in 1 to 3 sessions successfully induced high degree AV block in 79 patients, present at the time of discharge from hospital in 43 patients (50.5%). There were 3 cases immediately complicated by non-sustained ventricular tachycardia. Late complications (1 day to 1 month) included ventricular tachycardia (2 patients) septicaemia (3 patients) and pericarditis (1 patient). Sixty nine patients were followed up for an average of 12.9 +/- 10.0 months. There was one death from septicaemia due to infection of the pacemaker and two deaths at 5 and 6 months due to cardiac failure which had been present before the procedure. Fifty six patients were asymptomatic (81.1%), 27 with high degree AV block and 29 patients with (N = 19) or without (N = 10) antiarrhythmic therapy. There were 10 failures. This study shows that closed chest interruption of the normal AV conduction pathway is an effective and relatively safe alternative method of treating supraventricular tachycardias resistant to antiarrhythmic therapy. PMID- 3096239 TI - [Treatment of resistant ventricular tachycardia with endocavitary ablation combined with anti-arrhythmia agents]. AB - Catheter ablation was used in 26 consecutive cases of high risk ventricular tachycardia (VT) resistant to antiarrhythmic therapy. Seven patients were in permanent VT at the time of catheter ablation, three of them were moribund. There were 10 cases of arrhythmogenic right ventricular dysplasia, 9 cases of VT complicating chronic myocardial infarction, 4 cases of dilated cardiomyopathy, 2 cases of idiopathic VT and one congenital cardiac malformation. Ten patients required 2 or more sessions of catheter ablation to treat their arrhythmia. Three of the 4 early deaths (less than 1 month) were due to technical problems. Combined with antiarrhythmic drugs in 8 cases, catheter ablation brought the VT under control in the 22 remaining patients. The follow-up period ranges from 10 to 28 months (average follow-up longer than 17 months). Catheter ablation is a technique which is currently under evaluation. The very encouraging results obtained in this series suggest that it may replace surgery in the treatment of chronic refractory VT. PMID- 3096240 TI - [Hemodynamic development of the auricular communication of the ostium secundum and sinus venosus type. Study of 1189 patients]. AB - The haemodynamic data of 1,189 subjects with an atrial septal defect catheterised between 1953 and 1983 at the Marie Lannelongue Surgical Center and at Broussais Hospital was reviewed. Sixty per cent were under 20 years of age and 40 per cent were 21 to 75 years of age. The defect was an ostium secundum type in 89 per cent and sinus venosus in 11 per cent of patients. The commonest associated cardiac malformation was a partial anomalous pulmonary venous drainage which was present in 125 patients. Systolic and mean pulmonary arterial pressures decreased from a value slightly higher than normal between birth and 5 years of age to normal values between 5 and 20 years of age and then increased progressively to maximal values attained after 50 years of age (p less than 0.001). The proportion of patients with raised systolic and mean pulmonary arterial pressures increased with age after 20 years of age (p less than 0.001). A parallel increase in pulmonary blood flow was observed after 20 years of age, which was less marked than the increase in pressures, but nevertheless statistically significant (p less than 0.05). This increase in left to right shunt disappeared after 50 years of age. An increase in pulmonary resistances was observed after 20 years of age and persisted all through life (p less than 0.001). Two successive preoperative catheter studies were performed in 34 patients after a 6.4 +/- 4.7 years interval. In each patient, systolic pulmonary arterial pressures had increased and were significantly higher at the time of the second study (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096241 TI - [Prognosis of surgically corrected chronic aortic insufficiency]. AB - It is difficult to determine the surgical indications of asymptomatic chronic aortic regurgitation (AR). This study was undertaken in 205 patients with pure AR, operated between 1970 and 1982: 136 patients were symptomatic (Classes III and IV of the NYHA, +/- cardiac failure +/- angina, mean age: 49.5 years). Sixty nine asymptomatic patients (Classes I and II of the NYHA without cardiac failure or angina, mean age: 42 years). The prognostic value of 58 variables was studied in these two groups. The mortality during the first postoperative month was 14% in the symptomatic patients and the 5 year survival rate was 68.7%; this was significantly lower in patients with ECG changes of systolic left greater than or equal to ventricular overload, with radiological cardiomegaly (cardiotolerance index 0.60) with calcific aortic valve disease, with raised arterio-venous difference and/or low cardiac output, and with a low ejection fraction. In the asymptomatic group, the hospital mortality was zero and the 5 year survival rate 86.8%. This was significantly decreased in patients with an increased PR interval and a low cardiac index. It is possible that the small number of patients did not demonstrate the predictive value of left ventricular function in asymptomatic patients (a hypothesis suggested by the causes of secondary mortality which were the same in both groups of patients).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096242 TI - [Long-term course of syphilitic aortic insufficiency with ostial stenosis following surgical treatment]. AB - Syphilitic aortic insufficiency and coronary ostial stenosis is a rare condition. It was diagnosed in 8 patients referred for surgery. The infection, acknowledged in 3 cases, was contracted over 15 years prior to admission! The operative indication was aortic valve replacement in 6 cases (Stage II to IV dyspnoea) and coronary insufficiency in 2 cases (Stage III angina pectoris). Two cases of ostial stenosis were not identified at coronary angiography, illustrating the potential diagnostic pitfall of a disease which is often unrecognised nowadays. Preoperative echocardiography of the left main coronary artery, especially its intra-aortic segment, may be of value but was not performed in these old cases. Surgery consisted in aortic valve replacement and coronary revascularisation by decortication of the ostia or coronary bypass (1 case). The evolution was excellent in the 6 survivors, especially with respect to the anginal syndrome which was completely cured without associated treatment. A protocol of echocardiographic surveillance of the left main coronary artery has been instituted in these patients to detect any late postoperative changes after ostial decortication. PMID- 3096243 TI - [Variations in blood pressure at rest and during the day in 40 ambulatory hypertensive patients]. AB - Forty patients considered to be hypertensive on the basis of occasional blood pressure recordings obtained during three out-patient consultations (BP-C) underwent hourly blood pressure recordings throughout the day under standardized conditions at rest and lying down, but with normal daily activities between measurements. The average of the hourly measurements provides a basal blood pressure profile independent on non-standardizable factors of everyday life such as physical exercise and emotion without being artificially influenced by prolonged rest. The average ambulatory blood pressure (BP-A) is much lower than the BP-C. In particular, practically normal values (148-90) were observed in the group of patients with moderate but undiscutable hypertension (165/98) on the BP C readings. During the same day, variations of 10 to more than 30% of systolic and diastolic pressures were observed in over 3/4 of the patients; the highest values were recorded between 8 and 12 o'clock in about 70% of cases, most commonly at the first reading at 8 or 9 o'clock in the morning. This study shows that large variations of blood pressure are observed during the daytime even when repeated recordings are made under standardised conditions. This method of determining the day time blood pressure profile is a different approach to the study of hypertension than that based on ambulatory measurements made with a portable blood pressure recorder. PMID- 3096244 TI - [Primary tumors of the heart. Diagnostic, anatomic and therapeutic aspects]. AB - Primary cardiac tumours are rare. They are usually benign, the most common ones being left atrial myxomas. The authors report their experience of 16 cardiac tumours operated between 1978 and 1985. The patients were 12 adults and 4 children. The tumours were benign in 14 cases and malignant in 2 cases. Complete (14 cases) or incomplete ablation of the tumour was carried out under cardiopulmonary bypass with an early mortality of 6.25 per cent (1 case) and late mortality of 12.5 per cent (the two malignant tumours). The tumours were identified as myxomas in 11 cases, rhabdomyomas in 2 cases, fibroma in 1 case and malignant sarcomas in 2 cases. The average follow-up period of the 13 survivors is 30 months (range 4 months to 5 years) with excellent clinical and anatomical results. Clinical and paraclinical diagnosis of these tumours does not pose any major problems nowadays because of the reliability of the methods of investigation. However, the nature of the tumour is not always predictable and the operative findings are fundamental, not so much for the treatment which is relatively stereotyped but for the prognosis. Age is not a significant prognostic factor as excellent results may be obtained in the very young and the very old despite a sometimes precarious preoperative clinical condition. The benign or malignant nature of the tumour is the only real factor which affects the prognosis. PMID- 3096245 TI - [Doppler technics in the study of prosthetic valves]. AB - The authors studied a group of 120 patients and a total of 137 valvular prostheses by ultrasonic pulsed Doppler (3 MHz). Fifty three of these prostheses were also investigated with continuous wave Doppler. Clinical, phonocardiographic and echocardiographic examination revealed 99 normal and 38 abnormal prostheses, the latter group comprising 42 dysfunctions (9 obstructions and 33 regurgitations), all confirmed by invasive studies. The lesions were graded into 3 degrees of severity. The methods used were the recording of velocity signals and two- and three-dimensional mapping in the pulsed Doppler mode, and the calculation of the haemodynamic parameters derived from measurements of blood velocity in the continuous wave mode. Pulsed Doppler correctly diagnosed 92 out of the 99 normal prostheses. The maximum systolic pressure gradient in aortic valve prostheses was 16 +/- 6 mmHg; the average early diastolic pressure gradient of the mitral valve prostheses was 10.01 +/- 3.34 mmHg, with a mean diastolic gradient of 4.52 +/- 0.71 mmHg and a mean pressure half time of 0.09 +/- 0.02 sec giving an average valve surface area of 2.45 +/- 0.57 cm2. The sensitivity and specificity of the diagnosis of valve dysfunction were 95 and 92 per cent respectively with a satisfactory evaluation of the degree of severity in 88 per cent of cases. In the 3 mitral valve prostheses with obstruction, significant abnormalities of pressure half time and value surface area were detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096246 TI - [Treatment of anterior mitral valve prolapse by partial transposition of the posterior leaflet. Apropos of 7 cases]. AB - Seven patients aged 8 to 62 years with massive mitral regurgitation due to anterior leaflet prolapse related to rupture or elongation of the chordae tendinae underwent reconstructive mitral valvuloplasty between June 1984 and September 1985, consisting in transposition of a bandlet of the posterior leaflet and its chordae to the free edge of the anterior leaflet. Medium term results with 2 to 16 months follow-up (average 8 months) showed all patients to have returned to Class I of the NYHA Classification; 5 patients had no systolic murmur, a mild systolic murmur 1 and 2/6 was present in 2 cases. The quality of the repair was confirmed by pulsed Doppler examination in all patients and by catheterisation and angiography in 3 cases. This surgical technique offers a good solution to the problem of mitral regurgitation due to severe prolapse of the anterior leaflet caused by rupture or elongation of the chordae tendinae. PMID- 3096247 TI - [Cutaneous apoprotein B and coronary atherosclerosis]. AB - Cutaneous and plasma lipids (cholesterol and Apoprotein B) were studied in 2 populations (average age 57.5 years), one with pathological and the other with normal coronary angiography. Skin biopsy was performed during the incision of thoracotomy. The concentrations of Apo B and cholesterol in the skin were compared to those of plasma lipids, lipoproteins and apoprotein B for the diagnosis of atherosclerosis. This study showed that skin Apo B was the best marker of coronary atherosclerosis in patients with plasma Apo B concentrations of less than 1.3 g/l. The skin Apo B concentration was closely correlated to the presence but not to the severity of this arterial pathology. The cardiovascular risk factors of this population, studied separately and in a cumulative manner, confirmed the results of previously published reports. PMID- 3096248 TI - [Diltiazem and digoxin interaction. Development of digoxin plasma levels and electrocardiographic parameters in healthy subjects]. AB - In order to determine the interaction between diltiazem and digoxin, plasma digoxin concentrations and the principal ECG parameters (24 hour Holter monitoring) were measured in 10 healthy volunteers under basal conditions (P0), with 0.375 mg/day of digoxin (P1 = 17 days), during association with 240 mg/day of diltiazem (P2 = 17 days) and then again on digoxin alone (P3 = 10 days). The addition of diltiazem was associated with a 20.4% rise in plasma digoxin concentrations (0.59 ng/ml vs 0.49 ng.ml). There was no significant variation of plasma digoxin after withdrawal of diltiazem; in some cases it remained unchanged, in others it fell or continued to rise. During the administration of digoxin and diltiazem, the mean RR period and the duration of the maximal pauses increased (p less than 0.05); the RR interval also increased (p less than 0.01) but the mean QRS duration and the QTc interval did not change significantly with respect to their values on digoxin alone. After withdrawal of diltiazem, the PR interval was the only parameter to decrease significantly (p less than 0.05). These results suggest that patients receiving this drug association should be followed up carefully. PMID- 3096250 TI - [The mechanics of sarcomeres studied using laser diffraction. A study of relaxation]. AB - Myocardial tissues act as an optical filter to light. This is due to their regular striation--periodically alternating clear and dark anisotropic bands. When a narrow band of rat right ventricle is illuminated with a Helium-Neon laser (lambda = 633 nm) diffraction bands are observed, the spacing of which is inversely proportional to the sarcomere length. After muscular stimulation, the displacement of the diffraction bands allows measurement in real time of the contraction and relaxation of the sarcomeres. Sarcomere relaxation comprises two successive experimental phases, one rapid and the other one slow. The time constant of the rapid phase (tau 1) increases linearly with the total load; that of the slow phase (tau 2) decreases. The end of the rapid phase and tau 1 depend on the conditions of load. Our results suggest that the recaptation of calcium by the sarcoplasma reticulum and the affinity of troponine C for calcium depend on the level and changes of load. The affinity of TnC for calcium increases with high load and/or low amplitude of sarcomere shortening: it decreases with low loads and/or high amplitudes of sarcomere shortening. PMID- 3096249 TI - [Indications for permanent cardiac stimulation in 1986. Recommendations by the Cardiac Pacing Group of the French Cardiology Society]. PMID- 3096251 TI - [Experimental study of the subacute toxicity of mitoxantrone and doxorubicin in rats (subcutaneous and/or intraperitoneal route)]. AB - The aims of this study were to compare experimentally the subacute cardiotoxicity of a new anthracycline, mitoxantrone (MIT) with doxorubicin (ADM), the reference anthracycline drug. Seventy nine male rats were divided into 5 groups receiving one of the drugs or a placebo by subcutaneous (SC) or intraperitoneal (IP) injection, each week for 13 weeks. The surviving rats were sacrificed at the 21st week. Group I comprised 16 rats which received 2 mg/kg AMD-IP. The mortality rate was 50% between the 14th and 18th week. Twelve of the 16 cases had a haemorrhagic ascites. The heart was normal macroscopically and on light microscopy. However, electro microscopy showed moderate myocytic degeneration. Group II comprised 16 rats which received 0.6 mg/kg MIT-IP. Morality was 100% at the 11th week. Groups III and IV comprised 32 rats; half of the animals were given 0.6 mg/kg MIT-SC and the other half 0.4 mg/kg MIT-SC. The results were identical: good clinical tolerance, normal macroscopy. Three cases of lymphocytic myocarditis and in 4 out of 8 cases very mild myocardial degeneration on electron microscopy. Group V comprised 15 rats which were given NaCl 9% SC or IP; there were no complications. These results show that mitoxantrone given IP produced major peritoneal toxicity. On the other hand, it was well tolerated when given SC and only produced mild myocardial degenerative changes. PMID- 3096252 TI - [Spontaneous rupture of the ascending aorta. A surgically treated case]. AB - Rupture of the ascending aorta may follow thoracic trauma or complicate an aortic aneurysm or acute dissection. It is otherwise extremely rare. The authors report a case of spontaneous rupture of the ascending aorta occurring in a patient with a pre-existing incomplete rupture of the ascending aorta, and treated surgically. The clinical presentation was of acute dissection with pericardial effusion. This diagnosis was excluded by aortography with multiple views which showed abnormalities of the aortic wall: an abnormal notch, continuity of the internal wall and extravasation of the contrast medium. These abnormalities are often minimal but should be recognised and surgery proposed as this is the only chance of a favourable outcome. PMID- 3096253 TI - [Severe persistent sub-shift of the ST segment following cardioversion in ventricular tachycardia]. AB - The authors report a case of severe ST elevation after defibrillation which persisted for 6 days, suggesting acute myocardial infarction. The possible mechanisms of ST elevation after cardioversion and the unusually long duration of the ECG changes in this case are reviewed. The protective role of verapamil against myocardial damage is discussed. PMID- 3096254 TI - [A new cause of acute transitory auriculoventricular block: Lyme disease]. AB - A young man developed syncopal complete paroxysmal atrioventricular block (AVB) over a 36 hour period, on a background of 1st degree AVB which persisted for 6 weeks. During the 3rd week, electrophysiological studies showed an isolated prolonged AH interval. This episode followed skin and articular manifestations occurring one month after being bitten by a tick in Corsica. The clinical picture suggested Lyme's disease which was confirmed serologically. This condition transmitted bu Ixodes ricinus, a tick present in country districts, is due to spirochetal infection. It is characterized by a chronic migrating erythema, and may sometimes be complicated by severe AV conduction defects which are always regressive, as in our case. PMID- 3096255 TI - [Technic facilitating access to the peripheral veins in infants and children]. PMID- 3096256 TI - Enhanced thyrotropin response to thyrotropin releasing hormone in boys at risk for development of alcoholism. Preliminary findings. AB - Alcoholism is three times more prevalent in men than in women. We studied responses of thyrotropin to protirelin (thyrotropin releasing hormone) in nine sons and eight daughters of patients with familial alcoholism and in eight control boys and seven control girls. Basal and protirelin stimulated triiodothyronine, prolactin, and growth hormone concentrations were also measured. The controls were matched for age, sex, and past alcohol exposure with the index children. The sons of familial alcoholics had significantly higher basal thyrotropin levels, peak thyrotropin levels, and thyrotropin areas under the curve than did the control boys. The daughters of patients with familial alcoholism showed no differences from the control girls. Analyses of triiodothyronine, prolactin, and growth hormone concentrations revealed no differences between the index children and controls. We believe that this is the first report of a male-limited neuroendocrine difference between children of alcoholics and control children. Further studies are needed to elucidate the clinical significance of our preliminary findings. PMID- 3096257 TI - Stimulation of the mouse monocytes by Listeria monocytogenes. AB - The bacteria of Wellshimer's strain L. monocytogenes and their extract (LMA) showed in vitro the mitogenic activity which was demonstrated by increased proliferation of normal bone marrow cells and blood monocytes of the mouse strains resistant (C57Bl/6) and susceptible (DBA/2) to listeriosis. In the same experimental conditions the proliferation of spleen macrophages and resident peritoneal macrophages was not influenced. Besides, C57Bl/6 bone marrow cells, activated by live or killed L. monocytogenes, produced some growth factor for secondary bone marrow cell cultures. PMID- 3096259 TI - [Anticonvulsants. 1. Thiocarbamoylbutyroguanamines]. PMID- 3096258 TI - Coexisting Hodgkin's disease and mycosis fungoides. Immunohistochemical proof of its existence. AB - Hodgkin's disease and mycosis fungoides have been rarely reported in the same patient. This coexistence has been debated in the medical literature. We studied such a patient and report, to our knowledge, the first immunophenotypic evidence for such a coexistence. Reed-Sternberg cells and their variants stained with anti Leu-M1, Hefi-1, anti-Tac, anti-HLA-DR, and OKT9, but were negative for T cell markers 3A1, Leu-1, Leu-2a, and Leu-3a, a phenotype typical of Hodgkin's disease; infiltrating small lymphocytes were predominantly T cells and were phenotypically normal. In the skin lesions, cells with the phenotype of Hodgkin's disease were not present; the infiltrate was composed of helper T lymphocytes that were 3A1 negative, a phenotype characteristic of the malignant cells of mycosis fungoides. Unexpectedly, a dermatopathic lymph node from the same patient showed the presence of the Leu-M1 antigen on the majority of normal-appearing interdigitating reticulum cells; this was not the case with control dermatopathic lymph nodes from patients without a malignancy. The significance, implications, and possible interrelationships of the findings are discussed. PMID- 3096260 TI - Syntheses and biological activities of 2-(adamantylmethyl)benzimidazoles and imidazolines. PMID- 3096262 TI - [Comparative characteristics of the capillary bed of the temporal lobe and the mammillary bodies of the hypothalamus in man in relation to age]. AB - The data have been obtained on regional differences in structure of the capillary bed in the temporal cortex of the cerebrum (TCC) and in the papillary bodies of the human thalamus (PBHT) during various age periods. The capillary diameter and nuclear volume is greater in perivascular gliocytes of the TCC than in those of the PBHT. With ageing the capillary diameter and hypertrophy of the endotheliocytic nuclei is noted to increase in both areas of the brain. PMID- 3096261 TI - Effects of parenteral nutrition on cell cycle kinetics of head and neck cancer. AB - We attempted to determine whether nutritional supplementation with total parenteral nutrition (TPN) of malnourished patients with untreated squamous cell carcinoma of the head and neck alters tumor growth. Fourteen patients underwent biopsies of normal and malignant tissues and were then placed in either a control or adjuvant TPN group. Nutritional parameters and biopsies were repeated over the ensuing three to 17 days. Biopsy specimens were analyzed by flow cytometry for changes in the percentage of hyperdiploid cells (PHC) and aneuploidy. The PHC of tumor biopsy specimens in patients given TPN increased significantly from 15.1 +/ 2.0 to 27.3 +/- 3.3, while no such change occurred in normal mucosa. The PHC after TPN was significantly greater in the patients with cancer than that observed in the controls. These data demonstrate that TPN may have a stimulatory effect on tumor cell cycle kinetics in humans. PMID- 3096263 TI - [Decalcination of bone tissue at increasing concentrations of trilon-B salt]. PMID- 3096264 TI - Dietary effects on serum lipoproteins of dyslipoproteinemic baboons with high HDL1. AB - Some progeny of baboons (Papio sp.) selectively bred for a high response of serum cholesterol to an atherogenic diet have high serum levels of unusual lipoproteins with flotation rates of F degrees 1.20 9-28, intermediate between those of low and high density lipoproteins (HDL). They are similar to the fraction of HDL commonly called HDL1. We conducted a cross-over experiment to determine the roles of dietary cholesterol and saturated fat in eliciting these lipoproteins in the progeny of two affected sires. Half of the progeny of each sire manifested the trait (high HDL1 phenotype) while consuming an atherogenic diet and half did not (low HDL1 phenotype). While consuming a chow diet, high HDL1 progeny had higher total serum cholesterol concentrations than did low HDL1 progeny. This difference was exaggerated when the animals consumed diets enriched in either cholesterol or saturated fat (lard), and was greatest when the diet contained both. High HDL1 animals also had considerably higher serum apo E concentrations, and slightly higher serum apo A-I concentrations. High HDL1 progeny had much higher levels of cholesterol (twofold) and of apo A-I (three- to eightfold) in HDL1 fractions than did low HDL1 progeny. There were significant interactions between HDL1 class and both dietary cholesterol and saturated fat in their effects on other lipoprotein fractions. High HDL1 animals had an exaggerated elevation of cholesterol and apo B in very low, intermediate, and low density lipoproteins in response to dietary cholesterol. They also had an exaggerated elevation of cholesterol in the lighter HDL1 fraction (d = 1.041-1.053), and lesser elevation of cholesterol and apo A-I in HDL2. PMID- 3096265 TI - Virucidal chemical glutaraldehyde on alginate impression materials. PMID- 3096266 TI - Biological half-life, organ distribution and excretion of 125-I-labelled toxic peptide from the blue-green alga Microcystis aeruginosa. AB - M. aeruginosa is a bloom-forming cyanobacterium which is common in fresh-water lakes. It contains a potent hepatotoxin which when purified has been shown to be a heptapeptide of molecular weight 1019. The toxin was iodinated with 125I using the lactoperoxidase method, the labelled toxin administered intravenously to adult female rats and the half-life and organ distribution measured. The blood half-life after redistribution into extracellular pools was 42 min. The liver and kidneys showed accumulation of 21.7 +/- 1.1 and 5.6 +/- 0.2% of the dose respectively after 30 min. Little accumulation was observed in other organs and tissues. Small-intestinal contents and urine contained 9.4 +/- 6.1 and 2.9 +/- 1.2% of the dose respectively after 120 min. It was concluded that the liver is the main target organ for both accumulation and excretion of the toxin. PMID- 3096267 TI - Biochemical characterization for identification of ovine sarcosporidia. AB - Electrophoretic variants of enzymes from 100 individual macroscopic sarcocysts from sheep carcasses were examined to see if they could serve as genetic markers for the identification of ovine sarcosporidia. Of the 31 enzymes screened, 12 that represented single genetic loci were tested. There were two patterns of isoenzyme mobility, which differed at 7 out of 12 of the loci being studied, and corresponded to enzymes from either 'fat' or 'thin' cysts, indicating that these two sarcocyst types may be considered quite different species. In a parallel study, extracts of microscopic sarcocysts digested from sheep heart muscle were compared with those from macroscopic sarcocysts and found to have a distinct electrophoretic isoenzyme profile for each of four loci. PMID- 3096268 TI - Hay fever--a distressing environmental allergy. Part two. Royal Melbourne Hospital Pharmacy Department. PMID- 3096269 TI - IgA kappa multiple myeloma and lymphadenopathy syndrome associated with AIDS virus infection. AB - A 29 year old homosexual male presented with acute renal failure caused by acute myeloma. Subsequent investigation demonstrated antibody to the AIDS-associated virus human T-cell lymphotropic virus III, (HTLV-III/LAV/ARV). The association between lymphadenopathy syndrome and multiple myeloma is discussed. PMID- 3096270 TI - Heat sterilisation to inactivate AIDS virus in lyophilised factor VIII. PMID- 3096271 TI - Investigation of aberrant positive reactions to serological tests for bovine brucellosis. AB - Fifty cattle thought not to be infected with Brucella abortus but giving persistent positive serological reactions, were investigated. It was concluded that only one of these was infected since exhaustive bacteriological examination produced only one isolate of B. abortus (strain 19) and none of the herds of origin was subsequently shown to be infected with brucellosis. Antibody was detected in stifle joint fluid of 15 cattle, which may have been stimulated by the presence of Strain 19 antigen that persisted in collagenous tissue long after the viable organisms had been eliminated. PMID- 3096272 TI - Ovarian cancer: a comparison of two techniques for postoperative whole abdominal radiotherapy. PMID- 3096273 TI - A further contribution to the knowledge of mucopolysaccharidosis I H/S compound. Presentation of two cases and review of the literature. PMID- 3096274 TI - Solitary neurofibroma of foot--an unusual case with extensive calcification and ossification. PMID- 3096275 TI - [Artificial nutrition at home]. PMID- 3096276 TI - [Nutritional requirements in long-term artificial nutrition]. PMID- 3096277 TI - [Organization of a wide area management system]. PMID- 3096278 TI - [Total parenteral nutrition of cancer patients treated surgically]. PMID- 3096279 TI - [Tube feeding of patients with ENT tumors treated with radiotherapy]. PMID- 3096280 TI - [Parenteral nutrition of tumor patients at home]. PMID- 3096281 TI - [Artificial enteral nutrition as a supportive measure in simultaneous radiotherapy]. PMID- 3096282 TI - [Possibilities for the use of formula diets in tumor patients]. PMID- 3096283 TI - [Difficulties and complications in tube feeding]. PMID- 3096284 TI - [Metabolic complications in long-term parenteral nutrition]. PMID- 3096285 TI - [Risk of thrombosis of central venous catheters]. PMID- 3096286 TI - [Definition and requirements of enteral feeding]. PMID- 3096287 TI - [Infectious complications in long-term parenteral nutrition]. PMID- 3096288 TI - [Effectiveness and complications of parenteral nutrition at home]. PMID- 3096289 TI - [Advantages of ambulatory nutritional therapy from the viewpoint of health insurance]. PMID- 3096290 TI - [Legal aspects of ambulatory nutritional therapy]. PMID- 3096291 TI - [The family physician as a connecting link between the patient and the clinic]. PMID- 3096292 TI - [Experiences with artificial nutrition at home from the viewpoint of a patient]. PMID- 3096293 TI - [Home enteral nutrition in gastrointestinal diseases (Crohn disease)]. PMID- 3096294 TI - [Parenteral nutrition at home in chronic inflammatory bowel diseases and short bowel syndrome]. PMID- 3096295 TI - [Possibilities and limits of parenteral nutrition]. PMID- 3096296 TI - [Ambulatory parenteral nutrition of children]. PMID- 3096297 TI - [Fat emulsions in long-term parenteral nutrition]. PMID- 3096298 TI - [Nasogastric and nasoenteral catheter administration]. PMID- 3096299 TI - [Percutaneous endoscopic gastrostomy]. PMID- 3096300 TI - [Experiences with catheter jejunostomy]. PMID- 3096301 TI - [Implantation technics of catheters for long-term parenteral nutrition]. PMID- 3096303 TI - [Stability of prepared total nutrition solutions]. PMID- 3096302 TI - [Totally implantable catheter systems for long-term parenteral nutrition]. PMID- 3096304 TI - [Development of patient related parenteral nutrition solutions]. PMID- 3096305 TI - [Implementation of education and training of the patient]. PMID- 3096306 TI - [Management and control of the patient at home]. PMID- 3096307 TI - [Amino acid requirements in long-term artificial nutrition]. PMID- 3096308 TI - [Problems of parenteral nutrition at home from the viewpoint of the hygienist]. PMID- 3096309 TI - [Control of artificial nutrition at home]. PMID- 3096311 TI - Trehalase polymorphism in Drosophila melanogaster. PMID- 3096310 TI - Genetic and developmental characterization of the aldox-2 locus of Drosophila melanogaster. AB - The aldox-2 locus in Drosophila melanogaster has been shown to affect differentially three molybdoenzymes, aldehyde oxidase, pyridoxal oxidase, and xanthine dehydrogenase. These effects are most obvious at times surrounding the pupal-adult boundary, when the normal organism accumulates large amounts of these enzymes in their active form. This locus has been more precisely mapped genetically to 2-82.9 +/- 2.1, with complete concordance between the effects of all recombinant chromosomes on all three enzymes. The cytogenetic location has also been determined to be between 52E and 54E8, with the likelihood that it lies within the region 54B1-54E8. The aldox-2 mutant allele has no visible phenotype and is completely recessive for enzyme effects at all stages tested. Segmental duplication of this region, including the aldox-2+ allele, has no apparent effect on the visible phenotype or the enzymatic activity. The mutant aldox-2 allele has no effect on the developmental expression of two unrelated enzymes, 6 phosphogluconate dehydrogenase and NADP+-dependent isocitrate dehydrogenase. The effects of this locus on aldehyde oxidase, xanthine dehydrogenase, and pyridoxal oxidase suggest that this locus may code for a product involved in the synthesis of the molybdenum cofactor common to these enzymes. PMID- 3096312 TI - Peptidases in Drosophila melanogaster. I. Characterization of dipeptidase and leucine aminopeptidase activities. AB - Four major peptidases of Drosophila melanogaster have been described and distinguished by their electrophoretic mobilities, molecular weights, net electrical charges, and substrate specificities. The previously described leucine aminopeptidase, LAP D, consists of at least two isozymes, designated here LAP P and LAP G. In pupae most LAP activity results from LAP P (pupal); in larvae and adults, in contrast, most LAP activity results from LAP G (gut). These two LAPs may be separated by electrophoresis in the presence of the nonionic detergent Triton X-100. A specific assay for LAP P, which exploits the large difference between the net electrical charge of LAP P and that of LAP G, is described. The activity levels of two dipeptidases, Dip A and Dip B, were high in all the postembryonic stages examined. Specific assays for Dip A and Dip B were used to show that for each of these isozymes, the activity in an adult is proportional to gene dosage. PMID- 3096313 TI - Influence of a perinatal hypoxia on the carbonic anhydrase activity in different brain regions of the rat. AB - Homogenates of striatum, hippocampus and cerebral cortex of the rat brain were investigated for carbonic anhydrase activities. During ontogeny the enzyme activities increase with proceeding gliogenesis. At the 5th postnatal day (PD) prenatal hypoxia (17th day of gestation (GD)--birth) is followed by a 4-fold increase of carbonic anhydrase (CA) activity in the hippocampus. After postnatal hypoxia (2nd-10th day of life) CA activity in all investigated brain regions rise. At the 11th PD the values were 190 (cerebral cortex), 242 (striatum) and 176 (hippocampus) per cent of control. Noradrenaline (10(-6)M) enhanced CA activity in cerebral cortex and hippocampus about 2-fold. Dopamine (10(-6)M) caused an increase in the striatum up to 210% of control. The increased CA activity after hypoxia is assumed to be a functional response to activation of the glia by catecholamines. PMID- 3096314 TI - Antibodies prepared to Bacillus cereus phospholipase C crossreact with a phosphatidylcholine preferring phospholipase C in mammalian cells. AB - Antibodies against Bacillus cereus phospholipase C were prepared in rabbits and used to affinity purify a phosphatidylcholine-preferring phospholipase C from a human monocytic cell line. Affinity chromatography resulted in an approximately 3000-fold, one-step enrichment of phospholipase C. The human enzyme had an apparent molecular mass of 40,000 daltons as determined by SDS gel electrophoresis. Western blotting analysis demonstrated that this protein interacted specifically with the rabbit antibody raised against bacterial phospholipase C. The purified enzyme preferred phosphatidylcholine as a substrate, was neutral pH active and was inhibited by EGTA. These studies demonstrate that antibodies raised against bacterial phospholipase C may be useful in purifying phospholipase C from a human source. PMID- 3096315 TI - Hydroperoxide-dependent epoxidation of 3,4-dihydroxy-3,4 dihydrobenzo[a]anthracene by ram seminal vesicle microsomes and by hematin. AB - Addition of arachidonic acid to ram seminal vesicle microsomes oxidizes 3,4 dihydroxy-3,4-dihydrobenzo[a]anthracene (BA-3,4-diol) to five more polar products. Four of the products are identified by chromatographic and spectroscopic analysis as tetrahydrotetraols, which are solvolysis products of dihydrodiolepoxides. The fifth product is a 10-methyl ether formed by methanolysis of the anti-diolepoxide. Quantitation of the individual products indicates that anti-diolepoxides predominate over syn-diolepoxides by approximately 2:1. Identical product profiles are detected from the reaction of BA-3,4-diol with hematin and 13-hydroperoxy-octadecadienoic acid in the presence of Tween 20. No other products are detected in either system, which indicates that peroxyl radicals oxidize BA-3,4-diol exclusively by epoxidation of the 1,2 double bond. The stereochemical and regiochemical differences between oxidation of BA-3,4-diol by peroxyl radicals and cytochrome P-450 are dramatic and suggest that BA-3,4-diol is uniquely suited as a probe to quantitate peroxyl radical dependent epoxidation in vitro and in vivo. PMID- 3096316 TI - Inhibition of calcium transients in cultured vascular smooth muscle cells by pertussis toxin. AB - Effects of pertussis toxin on Ca2+ transients in rat arterial smooth muscle cells in primary culture were monitored, using quin 2-microfluorometry. In the presence or the absence of extracellular Ca2+, norepinephrine, histamine, caffeine and high extracellular K+ induced elevations in cytosolic Ca2+ concentration. Cytosolic Ca2+ elevations induced by norepinephrine and histamine were inhibited by pretreatment of the cells with pertussis toxin, time- and dose-dependently. However, elevations induced by caffeine and K+-depolarization were unaffected by the pretreatment with this toxin. Thus, it is suggested that GTP binding protein, a pertussis toxin substrate and involved in the receptor-mediated cytosolic Ca2+ transients, is not involved in transient elevations in cytosolic Ca2+ induced by caffeine and K+-depolarization in cultured vascular smooth muscle cells. PMID- 3096317 TI - Cloning and expression of a cDNA encoding a catalytically active fragment of calf thymus DNA polymerase alpha. AB - A calf thymus cDNA expression library was constructed in the EcoRI site of lambda gt11 and probed with an antibody raised against calf thymus DNA polymerase alpha. Three classes of antibody-reactive clones were isolated. The largest class carried a 1.9 kilobase calf cDNA insert and expressed a 165-175 kilodalton beta galactosidase:calf fusion protein which displayed DNA polymerase activity. The characteristic responses of the polymerase activity to alpha-specific inhibitors and antibodies identified the 1.9 kilobase cDNA as a sequence specifically derived from the structural gene encoding the pol alpha catalytic core. PMID- 3096318 TI - Purification and partial characterization of two extracellular endoglucanases from Cellulomonas fermentans. AB - Avicelase assay of gel slices after non-denaturing polyacrylamide gel electrophoresis of concentrated supernatants from Cellulomonas fermentans revealed four active bands. One of them corresponded to the principal active band on CM-cellulose. Among the three others, at least one did not correspond to any active band on CM-cellulose and might reflect the presence of an exoglucanase (EC 3.2.1.91). The active band on CM-cellulose was composed of two endoglucanases (EC 3.2.1.4), called CFA and CFB, which we purified by the means of DEAE-Trisacryl chromatography and high performance liquid chromatography (anion exchange chromatography and gel chromatography). These two monomeric enzymes differ in their molecular weights (40,000 and 57,000 for CFA and CFB, respectively) and in their catalytic constants in the reaction with CM-cellulose (Km were 1.5 g/l and 59 g/l for CFA and CFB, respectively), but have similar modes of action on this substrate and similar substrate specificities. PMID- 3096319 TI - Relationship between the inhibition of adenylate cyclase by pentobarbital and the functional coupling of Ns and the catalytic unit. AB - The effect of barbiturate on adenylate cyclase system was examined in rat brain. Pentobarbital inhibited the enzyme activities in both synaptic membrane and solubilized catalytic unit of the system in dose and time-dependent manners. The inhibitory effect of pentobarbital was more potent on the activation of the system by NaF-AlCl3 than on the basal activity. The inhibitory effect, however, was less in the synaptic membrane in which the catalytic unit was prestimulated through coupling with Ns by the treatment with NaF-AlCl3. Similar results were obtained with the solubilized preparation which was pretreated with guanylyl-5' imidodiphosphate before solubilization. On the other hand, the effect of pentobarbital was not modified by the treatment of the synaptic membrane with pertussis toxin. These findings indicate that barbiturates suppress primarily the activation of the catalytic unit through the coupling with guanine nucleotide binding stimulatory protein (Ns) without affecting the inhibitory protein (Ni). PMID- 3096320 TI - Mechanism of mannose toxicity. AB - Mannose toxicity in honeybees is due to a marked shortage of mannosephosphate isomerase that leads to a large accumulation of mannose-6-P and a marked depletion of ATP. Drosophila melanogaster and Ceratitis capitata are insensitive to mannose and have excess of mannosephosphate isomerase over hexokinase. 2 Deoxyglucose is as toxic as mannose for honeybees and is toxic also for the other insects studied, which supports the conclusion that the mechanism of mannose toxicity involves large accumulation of a hexosephosphate. PMID- 3096321 TI - alpha-Difluoromethylornithine induces differentiation of a human embryonal carcinoma cell line in vitro. AB - Human embryonal carcinoma cells could serve as a useful model system for analysis of early human development. A limited number of human embryonal carcinoma cell lines have been generated from in vivo tumors. We report here that alpha difluoromethylornithine, a specific enzyme-activated inhibitor of ornithine decarboxylase activity, can induce differentiation in human embryonal carcinoma cells. The differentiated phenotype could be distinguished from undifferentiated cells by altered cellular morphology, biochemical and cell surface antigenic properties. These results suggest that alterations in the intracellular levels of polyamines may play a role in human embryonal carcinoma cell differentiation, and possibly human embryogenesis. PMID- 3096322 TI - The human placenta: a novel source of inhibin. AB - Human placental extracts contain inhibin bioactivity and immunoactivity giving dose response curves parallel to a human follicular fluid inhibin standard. Inhibin bioactivity in vitro was neutralised by preincubation of extracts with antisera raised to pure bovine inhibin. Umbilical cord blood from term infants contained immunoactivity. Human placental inhibin differs from human ovarian inhibin in terms of its biological: immunological ratio. PMID- 3096323 TI - Induced rapid phospholipid methylation and arachidonic acid release by dimethyl sulfoxide-treated human promyelocytic leukemic HL-60 cells. AB - The incubation of undifferentiated promyelocytic HL-60 cells with DMSO resulted in the rapid transmethylation of phosphatidyl ethanolamine (PE) into phosphatidylcholine (PC) which was maximal at 60 secs. This rapid generation of PC was followed by a decrease of the methylated phospholipid and the release of arachidonic acid. Thus, the rapid DMSO-induced phospholipid methylation coupled with release of arachidonic acid (precursor for eicosanoids) prior to morphological evidence of cellular differentiation may represent early biochemical events which result in the generation of intracellular chemical signals which may program the promyelocytic cells into a differentiation mode. PMID- 3096324 TI - Combined effects of buserelin, estradiol and tamoxifen on the growth of MCF-7 human breast cancer cells in vitro. AB - The growth-stimulation of MCF-7 human breast cancer cells in vitro induced by 30 pM estradiol was inhibited both by the LHRH-agonist Buserelin and the anti estrogen Tamoxifen used as single agents. Combined administration of both drugs was less effective in this respect. In the presence of estradiol Buserelin had no effect on the pattern of [35S]methionine labelled secretory proteins when examined with one-dimensional gel electrophoresis, whereas the estrogen-induced progesterone receptor synthesis was inhibited. Thus with estradiol concentrations comparable to plasma values in medically castrated patients, the LHRH-agonist Buserelin can directly inhibit breast cancer cell growth in vitro. PMID- 3096326 TI - Calspectin (fodrin or nonerythroid spectrin)-actin interaction: a possible involvement of 4.1-related protein. AB - The calspectin/actin complex extracted from the bovine brain membrane crosslinks F-actin, resulting in the increasing viscosity of F-actin determined by low-shear viscometry. We demonstrated the presence of a protein factor in this complex, which regulated the calspectin-F-actin interaction in a Ca2+- and calmodulin dependent manner. Erythrocyte protein 4.1, but not synapsin I, mimics the function of this brain factor using a reconstitution system including purified calspectin, calmodulin and F-actin. In the brain complex, the Mr 120,000 and the Mr 80,000/77,000 polypeptides were detected to crossreact with anti-protein 4.1 antibody. PMID- 3096325 TI - GTP and GDP will stimulate platelet cytosolic phospholipase C independently of Ca2+. AB - The hydrolysis of [3H]phosphatidylinositol 4,5-bisphosphate (PIP2) by cytosolic phospholipase C from human platelets was determined. Cytosolic fractions were prepared from platelets that had or had not been preactivated with thrombin. Thrombin pretreatment did not affect cytosolic phospholipase C activity. In both cytosolic fractions, phospholipase C was activated by GTP and GTP gamma S. This action is observed in the presence of 2 mM EGTA. GDP was as effective as GTP in stimulating cytosolic phospholipase C in the presence of Ca2+ or EGTA. Partially purified phospholipase C obtained from platelet cytosol is activated by GTP, but not by GTP gamma S, in the presence of 2 mM EGTA. However, in the presence of 6 microM Ca2+, both GTP and GTP gamma S stimulated the partially purified phospholipase C. Our present information indicates that GTP and GDP have a direct effect on the cytosolic phospholipase C. PMID- 3096327 TI - Lack of excision of 4HAQO adducts from DNA by cell extracts that excise pyrimidine dimers. AB - A substrate of DNA containing 4HAQO adducts, suitable for studies of excision repair, was prepared by reacting calf thymus DNA with [3H]monoacetyl-4HAQO. A crude HeLa cell extract was prepared by the method of Mortelmans et al (Proc. Natl. Acad. Sci. U.S.A. 73, 2757, 1976). The cell extract would specifically excise pyrimidine dimers from UV-irradiated DNA but would not release 4HAQO adducts in an acid soluble form. This result points to different initial steps in the excision repair process for these two forms of damage even though much of the repair mechanism is common to both. PMID- 3096328 TI - Ethanol-enhanced transmembrane penetration of arachidonic acid and activation of the 5-lipoxygenase pathway in human leukocytes. AB - Enhanced penetration by ethanol of exogenous arachidonic acid into human leukocyte preparations results in the production of large amounts of eicosanoids including 5-, 12- and 15-hydroxyeicosatetraenoic acids as well as the leukotrienes C4 delta 6-trans-leukotriene B4, 12-epi-delta 6-trans-leukotriene B4, leukotriene B4 and 5(S), 12(S)-dihydroxyeicosatetraenoic acid. The production of these compounds is affected by the concentrations of both ethanol and arachidonic acid independently in a complex manner with stimulation at lower concentrations and later relative inhibition. It was shown that the resulting leukotriene B4 exhibited the same specific activity as exogenous arachidonic acid when labelled substrate was used. PMID- 3096329 TI - Phorbol diester synergistically stimulates agonist-induced lipoxygenase product formation in murine macrophages. AB - Murine peritoneal macrophages were preincubated with 12-O-tetradecanoylphorbol-13 acetate (100 ng/ml) and then exposed to various concentrations of calcium ionophore A23187. This combined treatment resulted in an elevated release of arachidonic acid metabolites that was synergistic in nature. Resolution of the [3H]products released into the medium revealed that the effect on the cyclooxygenase products 6-keto PGF1 and PGE2 were additive to less than additive (A23187 concentration dependent), the production of lipoxygenase products was synergistically enhanced, and the largest effect was on 12-HETE production. PMID- 3096330 TI - Appearance of membrane-bound tyrosine kinase during differentiation of HL-60 leukemia cells by immune interferon and tumor necrosis factor. AB - The effect of immune interferon (IFN-gamma) and recombinant tumor necrosis factor (rTNF-alpha) on cellular differentiation was investigated in human promyelocytic leukemia cell line HL-60. Both IFN-gamma and rTNF-alpha induced the appearance of the monocytic phenotype in a dose- and time-dependent manner as assessed by morphology, reduction of nitroblue tetrazolium and the induction of alpha naphthyl butyrate esterase. Utilizing a nondenaturing polyacrylamide electrophoretic assay, it was revealed that a membrane-bound tyrosine kinase activity accompanied the appearance of the differentiated cell type. These results suggest that the induction of membrane-bound tyrosine kinase activity by IFN-gamma and rTNF-alpha may be an important characteristic of monocytic differentiation. PMID- 3096331 TI - The role of guanyl nucleotide binding proteins in the formation of inositol phosphates in adrenal glomerulosa cells. AB - A non-hydrolysable GTP analogue enhanced the formation of [3H]inositol polyphosphates in permeabilized adrenal glomerulosa cells. Pertussis toxin, which ADP-ribosylated Ni, failed to influence angiotensin-induced formation of 3H labelled inositol phosphates and the incorporation of [32F]phosphate into phosphatidylinositol and phosphatidic acid. These results show that Ni is present and a G-protein activates phospholipase C also in glomerulosa cells, however, it is not Ni which couples angiotensin receptors to the enzyme. PMID- 3096332 TI - Functional antagonism between type I and type II interferons on human macrophages. AB - A three-day treatment with IFN-gamma enhanced up to 300% the capacity of human monocytes and macrophages to produce H2O2 during the respiratory burst. IFN-alpha or -beta (type I IFNs), which did not by themselves influence the burst, were found to antagonize the enhancing effect of IFN-gamma (type II IFN). The antagonism was concentration-dependent and required the presence of type I IFNs during the whole period of IFN-gamma pretreatment. These results suggest that the host defense function of mononuclear phagocytes may be controlled by the relative local concentrations of type I and type II IFNs. PMID- 3096333 TI - Endo-glycosidase F and peptide N-glycosidase F release the great majority of total cellular N-linked oligosaccharides: use in demonstrating that sulfated N linked oligosaccharides are frequently found in cultured cells. AB - Subtle modifications of N-linked oligosaccharides are known to mediate important biological functions. However, many of these modifications are destroyed by chemical treatments used to release oligosaccharides from the proteins. Therefore, enzymatic release of the intact, modified oligosaccharides is preferred. We have used a mixture of endoglycosidase F and Peptide: N-glycosidase F to release most, if not all, of the [2-3H]Man-labelled N-linked oligosaccharides from a wide variety of mammalian cell lines. This approach combined with biosynthetic radiolabelling could, therefore, be used to identify novel, rare or transient modifications of N-linked oligosaccharides. This treatment indeed released metabolically incorporated [35SO4] from each of 9 different cell lines demonstrating that sulfated N-linked oligosaccharides are much more common than previously believed. PMID- 3096334 TI - Effect of hyperglycemia on sorbitol and myo-inositol content of cultured rat conceptus: failure of aldose reductase inhibitors to modify myo-inositol depletion and dysmorphogenesis. AB - Growth retardation and dysmorphogenesis were seen in the rat conceptus following culture from day 9.5 to 11.5 of development in the presence of increased amounts of glucose. Sorbitol accumulated in the conceptus during the hyperglycemia whereas total protein, DNA, and free myo-inositol decreased. Similar glucose related compositional changes were present in separated embryos and extra embryonic membranes suggesting that all portions of the conceptus participate in the alterations. The aldose reductase inhibitors Sorbinil and Statil obtunded the rises in sorbitol but did not modify the increased incidence of malformations and the fall in DNA, protein and myo-inositol. Thus, the aldose reductase pathway may function in the early post-implantation rat conceptus but the resultant accumulation of sorbitol does not appear to contribute to the growth-retarding, dysmorphogenic, and myo-inositol-depleting effects of hyperglycemia. PMID- 3096335 TI - Glucoside formation as a novel metabolic pathway of pantothenic acid in the dog. AB - Metabolism of pantothenic acid (PaA) in beagle dogs was investigated. The dogs excreted 12.3% of the dose in the urine within 24 hr after a single oral administration of [3H]PaA (3 mg/kg). High performance liquid chromatographic analysis of the urine showed the presence of unchanged vitamin and a major metabolite, which accounted for 60.2 and 39.8% of the urinary radioactivity respectively. Although the metabolite was hydrolyzed by treatment with beta glucuronidase or acid phosphatase, it was found that this hydrolysis resulted from the actions of beta-glucosidase contained as a contaminant in these enzyme preparations. beta-Glucosidase completely hydrolyzed the metabolite to generate PaA and glucose. The metabolite was isolated and subjected to GC/MS and NMR analyses. It was identical to synthetic PaA beta-glucoside, 4'-O-(beta-D glucopyranosyl)-D-pantothenic acid. It was shown by the use of dog liver microsomes that PaA underwent beta-glucosidation in the presence of uridine diphosphate glucose (UDPG). It is proposed that beta-glucosidation by UDP glucosyltransferase is a novel metabolic pathway of PaA in the dog. PMID- 3096336 TI - The inducibility and ontogeny of rat liver UDP-glucuronyltransferase toward furosemide. AB - Furosemide (F) conjugation with glucuronic acid is the main pathway of F metabolism in humans and experimental animals. In order to study rat liver microsomal UDP-glucuronyltransferase (UDP-GT) activity towards F we developed an in vitro assay in which the conjugation product, furosemide 1-0-acyl glucuronide (FG) was separated and quantitatively determined by reverse phase high pressure liquid chromatography. The optimal conditions of the reaction were established and the apparent Km for F and UDP-glucuronic acid (UDPGA) were 0.22 and 1.76 mM, respectively. Substrate inhibition of UDP-GT toward F occurred at F concentrations higher than 1.5 mM. Developmental changes in F glucuronidation were compared to the ontogeny of UDP GT activity toward two other acceptors, 1 naphthol and estrone that are known to have different patterns of maturation. F glucuronidation was 26% of adult activity at 18 days of gestation, reached 48% at birth and gradually increased to 250% of adult activity at 22 days of age. Glucuronidation of 1-naphthol and estrone attained 87% and 44% of adult activity at 22 days of gestation, 37% and 66% in six-day-old rats and 100% and 427% of adult activity in 22-day-old rats, respectively. The effect of 3 methylcholanthrene (3-MC), phenobarbital (PB) and pregnenolone-16 alpha carbonitrile (PCN) on F UDP-GT was studied and compared to their effect on 1 naphthol and estrone glucuronidation. PB, 3-MC and PCN increased F-UDP-GT activity to 208%, 282% and 342% of vehicle-treated animals, respectively, while F pretreatment did not affect the conjugation of F. In comparison, 1-naphthol glucuronidation was preferentially induced by 3-MC (4.4-fold of control) while estrone glucuronidation was induced by PB and PCN (4.9- and 2.5-fold of control, respectively). These studies suggest that several forms of UDP-GT activities, which differ in their ontogeny and inducibility patterns, are involved in the glucuronidation of F in vitro. PMID- 3096337 TI - Lack of hepatotoxic interaction between the anticonvulsant drugs phenytoin, sodium valproate and phenobarbital in the rat. PMID- 3096338 TI - Colchicine selectively inhibits lactase expression by rat enterocytes. AB - One early aspect of enterocyte differentiation involves the appearance of digestive enzymes in the brush border membrane during cell migration from intestinal crypts onto villi. Present experiments describe how small amounts of colchicine selectively affect this particular aspect of enterocyte development. Oral ingestion of approximately 50 micrograms colchicine per day halves lactase activity in intestinal homogenates without affecting sucrase, maltase or alkaline phosphatase activities. This inhibition, which is completely reversible, takes about 48 hr to become complete. Further analysis of this effect by quantitative cytochemistry shows colchicine to reduce the maximal rate at which lactase activity appears in the brush border membrane. This reduction takes place without substantially affecting enterocyte migration rate or the time taken to fully complete lactase development. The possibility is discussed that small amounts of colchicine can selectively inhibit lactase biosynthesis in both crypt and mature villus enterocytes. PMID- 3096339 TI - Immunochemical and functional characterization of UDP-glucuronosyltransferases from rat liver, intestine and kidney. AB - Glucuronidation of various substrates in hepatic, intestinal and renal microsomes of control, phenobarbital (PB), 3-methylcholanthrene (3MC) and Aroclor-1254 (A1254) pretreated rats was investigated. UDPGT activities tested could be divided in four groups on the basis of their tissue distribution and induction by PB or 3MC in liver microsomes. GT1 activities (1-naphthol, benzo(a)pyrene-3,6 quinol) are induced by 3MC in liver microsomes and are present in all tissues investigated. GT2 activities (morphine, 4-hydroxybipheynl) are induced by PB in liver microsomes and appear to be restricted to the liver and the intestine. UDPGT activity towards bilirubin, although induced by PB, can be detected in hepatic, intestinal and renal microsomes. UDPGT activity towards fenoterol is restricted to the liver and intestine and is not induced by PB, 3MC or A1254. The presence of inducible immunoreactive UDPGT isoenzymes in microsomes of liver, intestine and kidney of control and induced rats was demonstrated by immunoblot analysis using rabbit anti-rat liver-GT1 antibodies. Induction of both 54 and 56 kDa polypeptides in hepatitis, intestinal and renal microsomes by 3MC or A1254 was observed. Purification of UDPGT (1-naphthol as substrate) from intestinal microsomes to apparent homogeneity yielded a polypeptide with an apparent molecular weight of 54-56 kDa. The results indicate that 54 and 56 kDa UDPGT polypeptides are the major A1254 inducible isoenzymes in intestinal and renal microsomes. An increase in immunoreactive protein is correlated with a biochemically measurable increase in glucuronidation capacity for GT1 substrates. PMID- 3096340 TI - [Interaction of a synthetic fragment of the oncoprotein p21ras with cellular proteins]. AB - A decapeptide corresponding to residues 35-44(-Thr-Ile-Glu-Asp-Ser-Tyr-Arg-Lys Gln-Val-) of p21ras was synthesized. It was found that peptide causes precipitation of some proteins from the Triton X-100 lysate of NIH 3T3 EJ cells. SDS-PAGE demonstrated the presence of many proteins in this precipitate. The peptide labeled with [125I]Bolton-Hunter reagent specifically recognized four proteins of M. W. 27, 35, 50 and 85 kDa. The order of charged amino acid residues in the fragment 35-44 of p21ras is "complementary" to that of the substrate sequence of tyrosine-specific protein kinases (-Arg-X-X-Glu-Asp-X-X-Tyr-). It is suggested that p21ras proteins directly regulate phosphorylation of the target proteins of these kinases. A model for functioning of p21ras proteins predicts the presence in their structure of certain sites homologous to sequences recognizable by tyrosine-specific kinases. Indeed two such sites are present in the sequences of all p21ras proteins, namely the residues 88-92 and 104-108. PMID- 3096341 TI - Human synovial fibroblasts produce urokinase-type plasminogen activator. AB - The plasminogen activator produced by cultured human synovial fibroblasts was investigated both biochemically and immunologically. Stimulated either by all trans-retinoic acid or by monocyte-conditioned medium, these fibroblasts elaborated a plasminogen activator with electrophoretic mobility similar to that of urokinase (Mr = 52 kilodaltons), and which also had immunologic cross reactivity with urokinase. The plasminogen activator found in rheumatoid synovial fluids has been shown to be of the urokinase type. The findings reported here are consistent with the notion that synovial fibroblasts are a source of this proteinase. PMID- 3096342 TI - Influence on platelet activity and red cell fluidity of epoprostenol and two stable prostacyclin analogues in vitro. AB - Not only epoprostenol (prostacyclin, PGI2) but also the two stable prostacyclin analogues CG 4203 (oxacyclic) and CG 4305 (carbacyclic) cause concentration dependent inhibition of thrombocyte function: pseudopod formation and aggregation after stimulation with ADP, collagen and arachidonic acid are inhibited to an extent dependent on dose. ADP-induced aggregation is inhibited 45% by 10 nmol/l epoprostenol 47% by 50 nmol/l CG 4203 and 25% by 50 nmol/l CG 4305. Epoprostenol itself improves red cell fluidity to an extent dependent on concentration, but the two analogues tested show no such effect. PMID- 3096343 TI - Effects of 2-indolecarbohydrazides on thromboxane synthetase activity and on in vitro and ex vivo blood platelet aggregation. New selective inhibitors. AB - Platelet antiaggregatory action of 42 synthetic 2-indolecarbohydrazides was studied observing their actions on arachidonic acid (AA) and adenosine-5 diphosphate (ADP) induced platelet aggregation. Radioimmunoassay studies, following AA induced aggregation, measuring thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were carried out on those compounds whose previous activities included inhibition of AA induced platelet aggregation and inhibition of the second wave of aggregation using ADP as the aggregating agent. Those compounds which demonstrated inhibition of TXB2 with increased PGE2 were subsequently tested with PGH2 as the aggregating agent. Results of this work demonstrate that 3 of the 42 compounds have specific inhibitory activity for thromboxane synthetase. The most active compounds were 1-methyl-5-hydroxyindole derivatives. PMID- 3096344 TI - Health hazards in the workplace--an approach to surveillance. PMID- 3096345 TI - Antibiotic prophylaxis in intraoral wounds. AB - This study of 100 patients was undertaken to determine the efficacy of penicillin/erythromycin prophylaxis in the management of intraoral lacerations in the pediatric population. Only six patients of the evaluable population developed infections (6.4%). Two of these patients received antibiotic prophylaxis (4%), and the other four were control patients (8%) who developed wound infections (P = 0.41). Although most injuries were minor, if the injury was large enough to require suturing, the infection rate was slightly greater in the control group. Cross-product ratios for these small sample subgroups indicated that the likelihood of infection for non-prophylactically treated patient wounds of greater than 1 cm length and/or those requiring suturing was two to three times higher than that of patients treated prophylactically. Although no statistical significance could be ascribed to the observed differences of these post hoc categories, benefit from antibiotic prophylaxis may have been quantifiable in a study designed to assess only these major wounds utilizing a large sample size. In general, routine antibiotic prophylaxis appears unwarranted for simple intraoral lacerations in children, although it may be useful when the wounds are large enough to be sutured. PMID- 3096346 TI - Conservative therapy for missed esophageal perforation after blunt trauma. AB - An 80-year-old man was treated, non-operatively, for a distal esophageal perforation, diagnosed nine days after blunt thoracic trauma. Emergency department diagnosis was impeded by absence of mediastinal air; right chest-wall emphysema was thought to result from associated rib fractures. Conservative therapy consisting of nasogastric suction, intravenous antibiotics, right-chest tube drainage of a large communicating empyema cavity, temporary nasotracheal intubation with ventilatory support, total parenteral nutrition, and, finally, nasoduodenal intubation for elemental feeding were employed. This mode of therapy may be best in comparable elderly patients with esophageal perforation that is overlooked during the initial 24 hours after injury. Possibly, routine barium swallow in all patients with chest-wall emphysema and rib fractures would circumvent missed esophageal rupture after blunt trauma. PMID- 3096347 TI - [Does Giardia lamblia favor the proliferation of intestinal bacteria?]. PMID- 3096348 TI - [The cytopathic effect induced by strains of Pseudomonas aeruginosa producing hemolysin, leukocidin and proteases in Hep-2 cells]. AB - Pseudomonas aeruginosa is one of the leading causes of infection in compromised hosts, including patients with burns, cancer and natural and acquired immunodeficiency syndrome. Several exotoxins produced by P. aeruginosa, have been shown to contribute to the pathogenicity of the organism. Although their mode of action is known, little information is available about the interaction of these toxins with eukaryotic cells and the sequence of the pathological events. For these reasons, the early cytopathic effect (CPE) induced on Hep-2 cells infected by several P. aeruginosa strains was analyzed. Early cytotoxicity, (one h after infection) manifested by morphological evidence of cells death, followed exposure only to strains that produced one or more toxins such as leukocidin, haemolysins and proteases, and seems to be a multifactorial effect. In fact, each one of these virulence factors may induce CPE in late but not early stage. PMID- 3096349 TI - The purification and characterization of a beta-glucosidase from Alcaligenes faecalis. AB - The beta-glucosidase from Alcaligenes faecalis has been purified to homogeneity (880-fold purification, 11% yield) using a combination of classical techniques and medium pressure ion-exchange chromatography. It is a dimeric enzyme of monomer molecular weight 50,000 and has no specific requirement for divalent metal ions. It has a high specificity for beta-glucosides and hydrolyses a wide variety of different chemical types wit retention of configuration at the anomeric centre. It has no exo-beta-1,4-glucanase activity. It is reversibly inhibited by a variety of sugars which have been shown previously to be very active against glucosidases, suggesting a normal mechanism of action. Measured Km values for cellobiose and p-nitrophenyl beta-D-glucopyranoside are quite low (0.70 and 0.08 mM, respectively), making this a good choice for cocloning into a cellulase system optimized for glucose production. PMID- 3096350 TI - Oral L-carnitine supplementation in low-birth-weight newborns: a study on neonates requiring combined parenteral and enteral nutrition. AB - Effect of L-carnitine supplementation on plasma ketone body (KB) and triglyceride (TG) concentrations was studied in ten premature infants requiring combined enteral and parenteral nutrition. At the second week of life (9 to 14 days of age) the infants were randomly divided into two groups. Five of them (plasma carnitine value, 33.77 +/- 2.48 mumol/l; mean +/- SEM) received oral L-carnitine supplementation (60 mumol/kg daily) added to pasteurized pooled human milk for seven consecutive days; additional five (plasma carnitine value, 36.70 +/- 5.19 mumol/l) served as controls. Composition of the daily diet was nearly constant in the study period. On the seventh day, prior to an Intralipid infusion, plasma carnitine and ketone body levels were significantly increased in the supplemented group as compared to controls or to previous values of the same group. In response to lipid infusion the fat load induced ketone body production was significantly higher in the supplemented group as compared to controls, whereas the triglycerides reached higher levels in the control group. It is suggested that L-carnitine supplementation in low-weight newborns promotes ketone body formation from endogenous stores as well as from exogenous fat supply, and thus may enhance triglyceride utilization. PMID- 3096351 TI - The effect of aspirin on protein breakdown in septic man. AB - In pathological states associated with hypermetabolism, such as acute sepsis, there is marked negative N balance. It has been suggested that the pathway for this response is via leukocyte pyrogen (interleukin I) acting on cyclooxygenase to stimulate prostaglandin release, which then stimulates proteolysis via the lysosomal pathway. In vitro, cyclooxygenase inhibitors decrease proteolysis in muscle tissue from septic rats. We tested this hypothesis in vivo in severely septic patients by using aspirin as the test cyclooxygenase inhibitor. Septic patients (n = 4) were given a primed, constant infusion (183 mg prime, then 37 mg/hr) of 15N-labeled urea for 6 hr to obtain a blood [15N]urea plateau. Blood samples were taken every 30 min. At 180 min 1500 mg of aspirin was given po. If aspirin inhibited protein breakdown, the plateau level should rise, since less cold urea derived from protein breakdown will enter the urea pool. Aspirin did not cause any change in either the BUN concentration, its 15N enrichment, or any of the plasma amino acids. In conclusion, cyclooxygenase inhibition by aspirin in vivo does not decrease protein breakdown in hypercatabolic septic patients. PMID- 3096352 TI - Studies on mitochondria from dystrophic skeletal muscle of mice. AB - Mitochondrial respiration and oxidative phosphorylation were compared in normal and dystrophic mouse skeletal muscles. To obtain the maximum respiration control ratio (RCR) and adenosine diphosphate/oxygen (ADP/O) ratio from isolated muscle mitochondria, it is found that there is an advantage in having a low concentration of proteinase and EGTA present in the medium during preparation of mitochondria by centrifugation fractionation. Using pyruvate, acetylcarnitine, and palmitylcarnitine as substrates for oxidation, a highly significant reduction (40-60%) is shown in oxygen uptake by dystrophic muscle mitochondria as compared to normal muscle mitochondria. Studies of the integrity of the oxidative phosphorylation apparatus in these samples showed that there is a reduction of the RCR and ADP/O ratio in dystrophic muscle mitochondria as compared to normal muscle mitochondria. PMID- 3096354 TI - Study of platelet function in a calf with artificial ventricles attached to an ex vivo shunt. PMID- 3096355 TI - Effect of diphosphonate binding to collagen upon inhibition of calcification and promotion of spontaneous endothelial cell coverage on tissue valve prostheses. AB - A noncalcifying drug, aminodiphosphonate, was immobilized on pericardial collagen to inhibit calcification. The parameters of ADP binding were optimized by using labeled tracer. The effects of the detergents, Triton X-100 and sodium dodecyl sulfate, pH, and temperature on ADP binding to collagen in fresh pericardium, and stabilization of ADP-collagen bond by borohydride (BH) reduction, were optimized. These studies indicate that pretreatment of pericardium with SDS and TX-100 increases ADP binding three- to fivefold. Three-step cross-linking via Schiff base reactions between collagen, ADP, and cross-linking via Schiff-base reactions between collage, ADP, and glutaraldehyde gives a high value of 30 to 35 molecules of ADP per collagen in pericardium. Twenty-five millimeter tissue valves were made with detergent (1% SDS, 1% TX-100) treated ADP-bound pericardium and implanted in the mitral annuli in calves, which were killed at 60 days post implantation. Regional calcium deposition was measured with atomic absorption spectrometry. The calcium level (micrograms/mg of tissue) in components of control and four processed valves were determined. Regional platelet deposition on zones of leaflets and components of tissue valves were quantified with 111In labeled autologous platelets. The calcium levels in thrombus and flexion zones of treated valves are lower than that in the control valve. SEM studies of leaflet surfaces at 60 days indicate that these treatment processes reduce calcification and promote spontaneous cell coverage on leaflets around the smooth surface of the outflow tract. PMID- 3096353 TI - HDL-cholesterol sparing and APO-B removal in recycled cascade plasmafiltration. PMID- 3096356 TI - Lympho-monokine disorders and peritoneal fibroblast proliferation in CAPD. PMID- 3096357 TI - P-450 activity in monolayer cultures of hepatocytes seeded in polystyrene tissue culture dishes. PMID- 3096358 TI - Buffer balance in bicarbonate hemodiafiltration. PMID- 3096359 TI - Coagulation and fibrinolysis in chronic renal failure. Change in tissue-type plasminogen activator activity. PMID- 3096360 TI - Ventilatory impact of partial extracorporeal CO2 removal (PECOR) in ARF patients. PMID- 3096361 TI - Method of pulmonary and membrane lung gas exchange measurement during extracorporeal membrane oxygenation. AB - A method for measuring simultaneous MemL and NatL gas exchange during neonatal ECMO has been described. Closed-circuit spirometry techniques were used for both measurements. This technique demonstrated minimal pulmonary gas exchange at low airway pressures prior to pulmonary recovery and measured the gas exchange of metabolism in these critically ill neonates. PMID- 3096362 TI - Extracorporeal elimination of carbon dioxide using a surface-heparinized veno venous bypass system. PMID- 3096363 TI - Effect of CAVH membrane types on drug-sieving coefficients and clearances. PMID- 3096365 TI - Arachidonic acid metabolism by polymorphonuclear leukocytes in psoriasis. PMID- 3096364 TI - Continuous infusion of fentanyl or alfentanil for coronary artery surgery. Plasma opiate concentrations, haemodynamics and postoperative course. AB - Nine patients received a mean total dose of 110 micrograms kg-1 of fentanyl and 10 patients received alfentanil 1379 micrograms kg-1 as a continuous infusion during coronary artery bypass grafting (CABG). Circulatory stability was well maintained through the induction of anaesthesia and a similar cardiovascular course was achieved with both agents, with the exception of small differences in heart rate and cardiac index immediately before tracheal intubation. Similar haemodynamic responses to sternotomy, cardiopulmonary bypass and awakening from anaesthesia were found with both analgesics. Although the times to awakening and extubation were somewhat shorter in patients receiving alfentanil, the differences between the groups were not significant. With the continuous infusion techniques, plasma opiate concentrations could be maintained well above the awakening values during cardiopulmonary bypass. In a total dose ratio of 1:13, fentanyl and alfentanil produced similar haemodynamic profiles and clinical courses in patients undergoing CABG. PMID- 3096366 TI - Disappearance of factor VIII:C antibodies in patients with haemophilia A upon frequent administration of factor VIII in intermediate or low dose. AB - In 18 haemophilia A patients with antibodies against factor VIII:C (F VIII:c) the effect of regular treatment with factor VIII (F VIII) in intermediate or low dose was studied. All patients with previous maximal F VIII:c antibody levels between 5 and 60 Bethesda Units per millilitre (BU/ml) showed a decrease of antibody level and normal F VIII recovery within 1-2 months. From nine patients with previous maximal antibody levels above 60 BU/ml four showed a decrease of antibody level within 2-26 months. In four young patients F VIII prophylactic therapy was started or continued as soon as there was evidence of F VIII:c antibody activity. In three of these patients F VIII recovery normalized within a few months. PMID- 3096367 TI - Acquired aplastic anaemia: a PNH-like disease? AB - Bone marrow from 20 patients with aplastic anaemia at different stages of disease and from three patients with paroxysmal nocturnal haemoglobinuria (PNH) was incubated in isosmolar sucrose with 5% autologous serum prior to culture in methylcellulose. If fresh serum was used, colony formation by granulocyte macrophage colony forming cells (GM-CFC) and immature erythroid precursors (BFU E) was reduced to approximately 50% in all patients tested, at any stage of disease, including complete autologous bone marrow recovery. Heat inactivation and complement inactivation with EDTA completely abrogated this inhibitory serum effect. Selective inactivation of the classical, antibody dependent complement pathway with Mg2+ EGTA reduced the inhibitory effect by 50%. Complement sensitivity of haemopoietic precursors is a known feature of PNH. Since the majority of our patients did not have PNH as judged by a negative sucrose-test on mature erythrocytes, we conclude that, in aplastic anaemia, haemopoietic cells express a PNH-like defect at a primitive level. PMID- 3096368 TI - Mast cell leukaemia: evidence for bone marrow origin of the pathological clone. AB - A 57-year-old female patient, admitted for an acute abdominal syndrome, was found to have an extensive proliferation of mast cells both in the peripheral blood and the bone marrow. Cytochemical studies confirmed the mast cell characteristics of the pathological cell population, while the immunophenotype strongly suggested a bone marrow origin of this malignancy. The course of the disease was not affected by antiproliferative treatment and the patient, after progressive general deterioration, died of intractable haemorrhage. On both clinical and haematological criteria it seems possible to distinguish this rare case of primary mast leukaemia from the more common form of tissue mastocytosis with secondary leukaemia. PMID- 3096370 TI - Management of ipsilateral ptosis with hypotropia. AB - Thirty-one patients presented for surgical correction of unilateral hypotropia of the globe and blepharoptosis. The hypotropia and pseudoptosis were corrected by Knapp procedures. The Bell's phenomenon was thereby improved, allowing safe correction of the true ptosis, generally by an anterior levator resection whose magnitude depended on measured levator function. PMID- 3096369 TI - Ovulation after treatment with ethinyl-oestradiol and medroxyprogesterone acetate in a woman approaching premature menopause. Case report. PMID- 3096371 TI - Warburg (HARD +/- E) syndrome without retinal dysplasia: case report and review. AB - Warburg syndrome is a recently defined autosomal recessive oculocerebral syndrome. It was previously given the acronym HARD +/- E, indicating what were regarded as the pathognomonic features, namely hydrocephalus, agyria, and retinal dysplasia with or without encephalocele. We report the case of a male infant with the typical cerebral features of hydrocephalus, agyria, and pseudoencephalocele, but without retinal dysplasia. Peters' anomaly and optic nerve hypoplasia were the main ocular defects. We believe that anterior chamber defects and optic nerve hypoplasia are the ocular defects more directly related developmentally to the cerebral defects. Definition of ocular defects is important, since diagnosis and counselling rely heavily on ocular signs, which help to distinguish this syndrome from neural tube defects in general. PMID- 3096372 TI - Euglena gracilis chromatin: comparison of effects of zinc, iron, magnesium, or manganese deficiency and cold shock. AB - The effects induced by Fe, Mn, or Mg deficiency or cold shock on the DNA content and histones of Euglena gracilis have been examined and compared to those produced by Zn deficiency. The DNA content of the stationary-phase organisms used as controls is 2.1 micrograms/10(6) cells. The DNA of stationary-phase iron deficient (-Fe), magnesium-deficient (-Mg), manganese-deficient (-Mn), zinc deficient (-Zn), and cold-shocked (CS) cells is increased to 3.0, 4.6, 6.2, 3.8, and 3.8 micrograms/10(6) cells, respectively. The electrophoretic mobilities of proteins solubilized with 0.4 N H2SO4 from CS, -Fe, -Mg, and -Mn cells are nearly identical and are characteristic of the five histone classes, H1, H2A, H2B, H3, and H4. In contrast, no histones are found in the equivalent acid extract from Zn cells. The effect of micrococcal nuclease on chromatin from control, CS, and Zn cells was examined. The chromatin of CS cells is 1.2-fold while that from -Zn cells is 10-30-fold more resistant to micrococcal nuclease digestion than is the chromatin of control cells. Thus, the chromatin of cells grown in Zn-deficient conditions differs markedly from that of organisms cultured in media deficient in Fe, Mn, or Mg or exposed to cold shock. PMID- 3096373 TI - Chick neural retina N-acetylgalactosaminyltransferase/acceptor complex: catalysis involves transfer of N-acetylgalactosamine phosphate to endogenous acceptors. AB - Homogenates of embryonic chick neural retina prepared in 1% Triton X-100 have the ability to transfer N-acetyl[32P]galactosamine [( 32P]GalNAc) from beta-32P labeled uridine diphosphate N-acetylgalactosamine [( beta-32P]UDP-GalNAc) to endogenous macromolecular acceptors. The phosphotransferase activity sediments as three distinct peaks upon centrifugation on sucrose gradients. These peaks are coincident with the transferase/acceptor complexes previously described [Balsamo, J., & Lilien, J. (1982) J. Biol. Chem. 257, 345-354]. The parameters of the 32P transfer reaction closely parallel those observed with UDP-[3H]GalNAc as substrate when the densest particles, H, are used as a source of transferase/acceptors. Treatment of 3H- and 32P-labeled products with alpha-N acetylgalactosaminidase removes [3H]GalNAc residues and exposes 32P-labeled groups. These data suggest that the sugar-phosphate is transferred intact, resulting in a terminal phosphodiester linkage. The resistance of the macromolecular products to digestion by endoglycosidase F and its sensitivity to hydrolysis under mild alkaline conditions suggest that the alpha-linked sugar is transferred to an oligosaccharide chain attached to the protein core via an O serine or threonine residue. Characterization of the 32P- and 3H-labeled H particle products by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals a series of coincident high molecular weight polypeptides. PMID- 3096375 TI - Preparation of protein conjugates via intermolecular hydrazone linkage. AB - Proteins can be modified at their amino groups under gentle conditions to contain an average of three to six aryl aldehyde or acyl hydrazide groups. These two types of modified proteins at about 10 microM concentration condense with each other at pH approximately 5 to form conjugates linked by hydrazone bonds. Under proper conditions conjugates mainly of dimers and trimers in size or, if desired, higher oligomers can be obtained. The conjugates can be dissociated to their individual protein components by an exchange reaction with an excess of acetyl hydrazide. The reversible hydrazone bonds of conjugates can be reduced with NaCNBH3 to give stable hydrazide bonds. The stability of protein-hydrazone conjugates was found to be significantly greater than that of the model compound, the N-acetylhydrazone of p-carboxybenzaldehyde. This difference is believed to result from the presence of multiple hydrazone linkages in protein conjugates. PMID- 3096374 TI - X-ray diffraction analysis of the inactivation of chymotrypsin by 3-benzyl-6 chloro-2-pyrone. AB - The inactivation of chymotrypsin by 3-benzyl-6-chloro-2-pyrone has been studied. A covalent adduct is formed that deacylates slowly with a half-life of 23 h. X ray diffraction analysis at 1.9-A resolution of the inactivator-enzyme complex shows that the gamma-oxygen of the active-site serine (serine-195) is covalently attached to C-1 of (Z)-2-benzylpentenedioic acid, the benzyl group of the inactivator is held in the hydrophobic specificity pocket of the enzyme, and the free carboxylate forms a salt bridge with the active-site histidine (histidine 57). The conformational changes that occur in the protein as a result of complexation are described. It is proposed that formation of the salt bridge prevents access of water and, therefore, hydrolysis of the acyl-enzyme. PMID- 3096376 TI - Activation of latent RNAase by antibodies against rat liver RNAase inhibitor. AB - RNAase inhibitor was purified to homogeneity from rat liver. The purified inhibitor was identified by measuring the activity in gel slices after polyacrylamide gel electrophoresis under non-denaturing conditions. Antibodies were prepared by immunization of guinea pigs with the inhibitor. The antibodies formed single precipitin lines with free RNAase inhibitor and RNAase A-inhibitor complex that fused in a micro-Ouchterlony test. Partially purified IgG from immunized animals, but not control animals, inhibited the activities of the free inhibitor and the inhibitor in the complex. In the latter case, the RNAase inhibitor complex was dissociated and active RNAase was liberated. PMID- 3096377 TI - Mucus glycoprotein secretion by duodenal mucosa in response to luminal arachidonic acid. AB - The effect of luminal application of arachidonic acid on the alkaline secretion, prostaglandin generation, and mucus glycoprotein output and composition was studied in proximal and distal duodenum of conscious dogs. Surgically prepared duodenal loops were instilled in vivo for up to 2 h with saline (control) followed by various concentrations (12.5-100 micrograms/ml) of arachidonic acid. The experiments were conducted with and without intravenous pretreatment with indomethacin. The recovered instillates were assayed for the content of prostaglandin and HCO3-, and used for the isolation of mucus glycoprotein. Exposure of duodenal mucosa to arachidonic acid led to concentration-dependent increase in the output of HCO3- and prostaglandin generation. In both cases this response was greater in the proximal duodenum. Pretreatment with indomethacin caused reduction in the basal HCO3- and prostaglandin output, and prevented the increments evoked by arachidonic acid. The proximal and distal duodenum displayed similar basal output and composition of mucus glycoprotein. Comparable increases in these glycoproteins were also obtained with arachidonic acid, the effect of which was abolished by indomethacin. Compared to basal conditions, mucus glycoproteins elaborated in response to arachidonic acid exhibited higher contents of associated lipids and covalently bound fatty acids, and contained less protein. The associated lipids of mucus glycoproteins elaborated in the presence of arachidonic acid showed enrichment in phospholipids and decrease in neutral lipids. The carbohydrate components in these glycoproteins also exhibited higher proportions of sialic acid and sulfate. The changes brought about by arachidonic acid were prevented by indomethacin pretreatment, and in both cases the glycoprotein composition returned to that obtained under basal conditions. The enrichment of mucus glycoprotein in lipids, sialic acid and sulfate in response to endogenous prostaglandin may be of significance to the function of this glycoprotein in the hostile environment of the duodenum. PMID- 3096378 TI - Mephenytoin-type polymorphism of drug oxidation: purification and characterization of a human liver cytochrome P-450 isozyme catalyzing microsomal mephenytoin hydroxylation. AB - A genetic polymorphism causing deficient metabolism of the anticonvulsant drug mephenytoin occurs in 5% of the Caucasian and 23% of the Japanese population. By monitoring the activities of the two major oxidative pathways of mephenytoin metabolism in the column eluates, we have purified from human livers a cytochrome P-450 isozyme, P-450 meph, which exclusively and stereoselectively catalyzes the 4-hydroxylation of (S)-mephenytoin, the major pathway affected by the polymorphism, whereas P-450 meph was virtually devoid of catalytic activity for N demethylation of mephenytoin, the pathway remaining unaffected by the genetic deficiency. P-450 meph had an apparent Mr of 55 000 and a lambda max in the reduced CO-binding spectrum of 450 nm. Polyclonal rabbit antibodies against purified human P-450 meph almost completely inhibited the 4-hydroxylation of mephenytoin but had little effect on N-demethylation in human liver microsomes. In microsomes of liver biopsies of two subjects characterized in vivo as 'poor metabolizers' of mephenytoin, immunocrossreactive and immunoinhibitable material was observed with similar or identical properties to those of P-450 meph. There was no difference in the extent of the immunochemical reaction between microsomes of in vivo phenotyped poor metabolizers and extensive metabolizers of mephenytoin. These data suggest that P-450 meph is the target of the genetic deficiency and support the concept that a functionally altered variant form of P 450 meph causes this polymorphism. PMID- 3096379 TI - Non-competitive inhibition of ornithine decarboxylase by a phosphopeptide and phosphoamino acids. AB - In Tetrahymena pyriformis the cytosolic ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity is considerably inhibited by the presence of polyamines in the growth medium, while the nuclear ornithine decarboxylase is only slightly affected. Experimental evidence suggests that the presence of putrescine and/or spermidine elicits the appearance of non-competitive inhibitors of ornithine decarboxylase. One of the inhibitors has a molecular weight of 25,000 and properties of antizyme. In addition, two other low molecular weight inhibitors are extracted, one which is a phosphoserine oligopeptide, and the other which is phosphotyrosine. All inhibit non-competitively the homologous and heterologous (Escherichia coli and rat liver) ornithine decarboxylases. Similarly, non-competitive inhibition was obtained when the commercially available phosphoamino acids were tested against the already mentioned ornithine decarboxylases. PMID- 3096380 TI - Purification, stability and kinetic properties of highly purified adenosine deaminase from Bacillus cereus NCIB 8122. AB - Adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) from Bacillus cereus NCIB 8122 has been purified to electrophoretic homogeneity by ammonium sulfate precipitation, gel filtration through Sephadex G-100, DEAE-Sephadex A-50 chromatography and ion-exchange HPLC on DEAE-Polyol. The enzyme activity is stabilized (at temperatures from 0 degrees C to 40 degrees C) by 50 mM NH4+ or K+, while it is irreversibly lost in the absence of these or a few other monovalent cations. Glycerol (24% by volume) helps the cation in stabilizing the enzyme activity above 40 degrees C, but also exerts per se a noticeable protecting effect at room temperature. B. cereus adenosine deaminase displays the following properties: Mr on Sephadex G-200, 68,000; Mr in SDS-polyacrylamide gel electrophoresis, 53,700; optimal pH-stability (in the presence of 50 mM KCl) over the range 8-11 at 4 degrees C, and maximal catalytic activity at 30 degrees C between pH 7 and 10; Km for adenosine around 50 microM over the same pH range and Km for 2'-deoxyadenosine around 400 microM. PMID- 3096381 TI - The human colon carcinoma cell lines HT-29 and Caco-2: two in vitro models for the study of intestinal differentiation. PMID- 3096382 TI - New trends in cryoenzymology: probing the functional role of protein dynamics by single-step kinetics. AB - Cryoenzymology was initially used to slow down enzyme-catalyzed reactions so as to stabilize intermediates for further study. During the course of this early work, it became clear that cryoenzymology could be extended to other ends and some of these are described. First, the use of a cryosolvent on its own (or together with temperature) as a perturbant has allowed a resolution of the substrate binding steps of certain enzymes (myosin, D-amino acid oxidase, peroxidase and cytochrome P450). Second, by the use of cryosolvent and temperature, coupled with the classical physico-chemical perturbants, one can selectively modulate the various steps of an enzyme pathway. This approach can lead to an understanding of the mechanism of enzyme regulation. Finally, by carrying out experiments over a wide range of temperatures (-30 degrees C- +30 degrees C) and pressure (up to several kbars) in specially constructed fast reaction equipment, one can study the thermodynamic properties of the individual rate constants describing the interconversions of reaction intermediates. Experiments with creatine kinase, cytochrome P450 and peroxidase are described. The thermodynamic parameters delta H, delta G, delta S and delta V are thus measured and when this is done under different solvent conditions one can, at least within the theories available, attempt an approach to the problem of protein dynamics. PMID- 3096383 TI - Isolation of actin genes in Bombyx mori: the coding sequence of a cytoplasmic actin gene expressed in the silk gland is interrupted by a single intron in an unusual position. AB - To study the regulation of the gene(s) coding for the actin present in the microfilaments involved in the secretion of silk, we have probed a Bombyx mori genomic library with a Drosophila actin cDNA clone and selected 16 recombinant phages. They correspond to 3 different genomic fragments each containing a distinct actin coding sequence. Southern blots of genomic DNA probed with the cloned genes show that in Bombyx mori, there are at least 5 different actin genomic sequences. Two cloned genes A1 and A2 hybridize to a 1.7 kb long mRNA abundant in the carcass of the larva and thus probably code for muscle type actin. The third cloned gene, A3, hybridizes to two mRNAs of about 1.8 kb present in the silk gland and thus probably encodes a cytoplasmic actin. The coding sequence of this gene has been sequenced: it is almost identical to the Drosophila cytoplasmic actin genes but it has a single intron of 92 nucleotides within the codon 116, a position not observed in any other organism. PMID- 3096384 TI - Anti-messenger oligodeoxynucleotides: specific inhibition of rabbit beta-globin synthesis in wheat germ extracts and Xenopus oocytes. AB - Oligodeoxyribonucleotides complementary to the initiation region of rabbit beta globin messenger RNA were used to selectively inhibit translation in a wheat germ extract and in injected Xenopus oocytes. The oligonucleotides interacted specifically with their RNA target as shown by thermal denaturation studies of hybrids on nitrocellulose filters. The longest oligonucleotide used (17-mer) efficiently blocked translation both in vitro and in vivo. In contrast the shortest one (8-mer) exhibited only a limited effect. The translation block was specific. The synthesis of endogenous proteins in oocytes and that of alpha globin in the in vitro system were not affected by anti-beta-globin oligonucleotides. A non-complementary oligonucleotide had no inhibitory effect. PMID- 3096385 TI - Sequence similarities among the family of aminoacyl-tRNA synthetases. AB - Recent affinity labeling studies have led to the identification of lysine residues at the CCA binding site of tRNA in Escherichia coli methionyl- and tyrosyl-tRNA synthetases. The comparison of the labeled peptides to the known primary structures of the aminoacyl-tRNA synthetases reveals new sequence similarities among this family of enzymes. These similarities include a 'constant' lysine residue whose functional significance is discussed. Moreover, a systematic computer analysis was conducted to search for similarities between the aminoacyl-tRNA synthetases taken as pairs. PMID- 3096386 TI - Isolation and some properties of an arylamidase from Flavobacterium IIb. AB - A constitutive L-leucylarylamidase (EC 3.4.11) hydrolase able to cleave L aminoacyl-beta naphthylamide and L-aminoacyl-4 nitroanilide substrates, was isolated from sonicated cells of Flavobacterium IIb and partially purified with a 0.9% yield and a 159-fold recovery. Its molecular weight was estimated to be about 170,000 +/- 10%. This arylamidase exhibited optimum activity at pH 7.0 and 28 degrees C for the hydrolysis of L-leucine-4NA and is inhibited strongly by metal chelating agents, and to a weaker extent, by some sulfhydryl and reducing agents. Heavy metal ions: Cd2+, Zn2+, Cu2+, Hg2+ and Co2+, markedly inhibit it, and Zn2+ is a competitive inhibitor. This metalloenzyme, free of carboxypeptidase, proteinase and L-leucine aminopeptidase (L-leucylglycine substrate) activities, hydrolyzes aminoacyl-beta NA, aminoacyl-4NA and some dipeptides with unsubstituted amino groups of the L-configuration. The lowest Km values are associated with substrates having neutral or basic residues, with large side chains. PMID- 3096387 TI - Ovine beta-lactoglobulin messenger RNA: nucleotide sequence and mRNA levels during functional differentiation of the mammary gland. AB - The nucleotide sequence of ovine beta-lactoglobulin mRNA has been determined by chemical sequencing of two cDNA recombinant plasmids and primer extension products. Ovine beta-lactoglobulin mRNA consists of a 540 nucleotide coding region, flanked by 39 nucleotide 5' and 206 nucleotide 3' non-coding regions including a 20 nucleotide poly A tail. The deduced 180 amino acid sequence of pre beta-lactoglobulin is in agreement with the previously published amino acid sequence of signal peptide and mature protein. Northern blot analysis of poly A+ RNAs from the lactating mammary glands of porcine, rabbit and rat species, allowed us to identify a homologous RNA to beta-lactoglobulin mRNA solely in the porcine species. We also detected a mRNA transcript of a size similar to that of beta-lactoglobulin mRNA in hepatic poly A+ RNA from female rat liver treated by estrogens. Furthermore, we have examined the levels of beta-lactoglobulin mRNA during the functional differentiation of the mammary gland and after hormonal stimulation. During the last third of pregnancy, the expression of beta lactoglobulin gene is significantly more elevated than that of alpha s1- or beta casein whose mRNA levels were found to change very slightly during this period. Both beta-lactoglobulin and casein mRNAs showed a rapid response and a wide range of change in response to cortisol treatment. However, there was a significant difference in the rate at which these processes occurred, suggesting that beta lactoglobulin gene expression is regulated independently of the casein genes. PMID- 3096388 TI - Monoclonal antibodies to pancreatic stone protein. Radioimmunoassay and immunological comparison with trypsin 1. AB - Monoclonal antibodies were prepared against pancreatic stone protein, a protein which inhibits calcium carbonate precipitation. Two monoclonal antibodies designated D4 and 2E7 were characterized. Immunoadsorbant columns, obtained by linkage of these monoclonal antibodies to Affigel 10, have been used to isolate immunoreactive forms of pancreatic stone protein from nonactivated human pancreatic juice. These monoclonal antibodies permitted us to test the possible immunological relationship between pancreatic stone protein and human trypsin 1. No immunological similarity was found, in agreement with our previous results, and it was established that pancreatic stone protein is a novel protein and not a degradation product of human trypsin(ogen) 1. PMID- 3096389 TI - Translation of polyuridylic acid in lysed mitochondria. AB - After osmotic shock with 50 mM Tricine buffer (pH 7.9), isolated mitochondria from D. Melanogaster embryos are treated with a low concentration of Triton X-100 (25 micrograms/mg of protein). The lysed mitochondria are still capable of RNA and protein synthesis. While incorporation of labeled precursor is often higher in lysed than in intact mitochondria, neosynthesized proteins exhibit similar electrophoretic patterns. Studies of labeled precursor incorporation in the presence of various effectors indicate a better accessibility to the translation machinery in lysed mitochondria than in intact mitochondria. Such a system has proven capable of translating an exogenous synthetic mRNA, i.e., poly (U). PMID- 3096390 TI - The glucomannan system from Aloe vahombe (liliaceae). III. Comparative studies on the glucomannan components isolated from the leaves. AB - The polysaccharide mixture obtained by hot water extraction of Aloe vahombe leaves is composed of at least four different paritally acetylated glucomannans which differ in molecular weight, glucose to mannose ratios and acetyl contents. Furthermore, one fraction contains a small but significant amount of protein which could not be removed by gel filtration in a hydrogen-bond-breaking medium, by DEAE-Sephadex A-50 anion exchange chromatography, or by Sevag's method. PMID- 3096391 TI - Single-strand binding proteins from phage T4 and E. coli form higher order structures with poly(dT). AB - Complexes of poly(dT) with gene 32 protein from phage T4 or E. coli single-strand binding protein were digested by nuclease P1 from Penicillum citrinum. Protected fragments were analyzed by gel electrophoresis. In both cases, a series of bands was obtained corresponding to multiples of a repeat unit whose size was about 80 nucleotides. Such protected fragments could not be detected under the same experimental conditions when poly(dA) was used instead of poly(dT). The formation of nucleosome-like structures is discussed in relation to the higher affinity exhibited by single-strand binding proteins towards poly(dT). PMID- 3096392 TI - Detection of distinct receptors for native and acetylated low-density lipoproteins in human placental microvilli by ligand-immunoblotting. AB - Ligand-immunoblotting was used to detect distinct receptors for native low density lipoprotein and for acetylated low-density lipoprotein on microvillous membranes from human term placentas. Antisera directed against native and modified low-density lipoproteins were prepared in rabbits and their specificities were assessed by immunodiffusion and immunoelectrophoresis. The receptor for low-density lipoprotein was detected as a 160 kDa protein and that for acetylated low-density lipoprotein as a 200 kDa protein. These receptors were compared with their counterparts in cultured human skin fibroblasts, bovine adrenal cortex and J774 macrophage-like cells. This is the first investigation that visualizes the presence of receptors for both native and modified low density lipoproteins in a steroidogenic tissue. PMID- 3096393 TI - [Modification of swine pepsin and pepsinogen by p-nitrophenyldiazonium chloride]. AB - It was found that at pH 5.2 and 40-fold excess of p-nitrophenyldiazonium chloride the inhibitor incorporation into the porcine pepsin molecule involves 1.9 residues, one residue being bound to tyrosine 189. Besides, tyrosines 44, 113, 154 and 174 enter the reaction. Modified pepsin retains 25% of the native enzyme activity. In the pepsinogen molecule the degree of tyrosine 189 modification diminishes 5 times; of 1.5 inhibitor molecules incorporated into the protein 0.78 residues are bound to tyrosine 113. The potential proteolytic activity of modified pepsinogen towards haemoglobin cleavage makes up to 60% of the original one. It is concluded that the activation peptide in the pepsinogen molecule masks the substrate binding site bearing tyrosine 189, thus preventing its modification with p-nitrophenyldiazonium chloride. The activation peptide in the pepsinogen molecule is presumably located in the vicinity of the wide loop bend carrying tyrosine residue 113, which may be the reason for the decreased pKa value of this residue and of its increased reactivity in the azocoupling reaction. PMID- 3096394 TI - Drugs and acute renal insufficiency in the neonate. AB - Oliguria in the neonate usually reflects a fall in glomerular filtration rate (GFR) secondary to prerenal disturbances such as hypovolemia, hypotension, hypoxemia and cardiac failure, or to vasoactive drugs such as indomethacin and tolazoline. The action of such drugs on renal function is reviewed, as well as the pharmacological measures that can be tried to prevent or blunt their renal side effects. The efficacy and side effects of dopamine, furosemide and mannitol, frequently used in oliguric states due to either prerenal disturbances or to vasoactive drugs, are discussed. It is concluded that available data in newborn infants do not definitely prove the efficacy of dopamine and furosemide in preventing acute renal insufficiency and that, in neonates with established oliguria, administration of mannitol, dopamine and/or furosemide can be tried, with little hope, however, of markedly improving GFR. PMID- 3096396 TI - Pf1 virus particle dynamics. PMID- 3096395 TI - Effect of sonication on nucleotide-dependent light scattering changes in retinal rod outer segment suspensions. AB - Near-infrared light scattering from suspensions of rod outer segment fragments is a useful probe of visible-light-activated changes in peripheral membrane proteins in photoreceptor cells. Limited sonication of suspensions has been shown to increase the amplitude of light induced turbidity changes in the presence of guanosine triphosphate by a factor of 2. Further sonication led to a decrease in the signal amplitude by an order of magnitude. This reduction has been puzzling, since the activity of the GTP-binding protein (as measured by GTP hydrolysis turnover number) was unaffected by the range of sonication used. This effect of sonication is investigated here using a novel, Reticon-based apparatus that measures the angular distribution of scattered light from samples as small as 1 microliter. The results show that even at high rhodopsin concentrations (125 microM) with millimeter path lengths, significant amounts of unscattered light are transmitted by the samples. A simple phenomenological theory that assumes a constant fractional change in scattering power (15%), independent of amount of sonication, explains the effect of sonication on the angle dependence data as well as the original turbidity data. The results have general relevance for optimization of light-scattering studies of membrane systems. PMID- 3096397 TI - Relation between absorption half-life values of four novel sustained-release dosage forms of valproic acid in dogs and humans. PMID- 3096398 TI - [Metabolism of arachidonic acid in the thrombocytes of patients with periodic disease]. AB - Washed platelets of patients with familial Mediterranean fever (FMF) were incubated with I-14C arachidonic acid (AA). Only 10% of AA were transformed into thromboxane A2, 12(S)-12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE) and 12(S)-12-hydroxy-5Z,8Z,10E-heptadecatrienoic acid (HHT), which strongly indicates the suppression of platelet lipoxygenase and cyclooxygenase or the deficit in these enzymes in FMF. However, there were no noticeable alterations in AA platelet metabolism during attacks of fever and immediately after hyperbaric oxygenation used to relieve pain and fever. The data obtained suggest that arachidonic acid metabolism plays an important role in the pathogenesis of FMF. PMID- 3096399 TI - Mechanism of protein C-dependent clot lysis: role of plasminogen activator inhibitor. AB - The mechanism by which activated protein C stimulates fibrinolysis was studied in a simple radiolabeled clot lysis assay system containing purified tissue-type plasminogen activator, bovine endothelial plasminogen activator inhibitor (PAI), plasminogen, 125I-fibrinogen and thrombin. Fibrinolysis was greatly enhanced by the addition of purified bovine activated protein C; however, in the absence of PAI, activated protein C did not stimulate clot lysis, thus implicating this inhibitor in the mechanism. In clot lysis assay systems containing washed human platelets as a source of PAI, bovine-activated protein C-dependent fibrinolysis was associated with a marked decrease in PAI activity as detected using reverse fibrin autography. Bovine-activated protein C also decreased PAI activity of whole blood and of serum. In contrast to the bovine molecule, human-activated protein C was much less profibrinolytic in these clot lysis assay systems and much less potent in causing the neutralization of PAI. This species specificity of activated protein C in clot lysis assays reflect the known in vivo profibrinolytic species specificity. When purified bovine-activated protein C was mixed with purified PAI, complex formation was demonstrated using immunoblotting techniques after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. These observations suggest that a major mechanism for bovine protein C-dependent fibrinolysis in in vitro clot lysis assays involves a direct neutralization of PAI by activated protein C. PMID- 3096400 TI - Rh blood group-specific antibodies in immune hemolytic anemia induced by nomifensine. AB - Nomifensine (Merital, Alival; Hoechst, Frankfurt, FRG), an antidepressant drug, may cause immune hemolytic anemia (IHA) of the so-called immune complex type that is believed to occur by means of an innocent-bystander mechanism. In this report we describe findings that are not consistent with this mechanism in a patient with nomifensine-induced intravascular IHA associated with renal failure. In vitro studies showed a transitory positive direct antiglobulin test (DAT) due to IgG, IgM, and C3 fixation. The causative antibodies were found to be a drug independent IgM antibody in the serum and eluate that reacted only with E positive RBC, although the patient's RBC were E-negative; an IgG antibody in the serum and initial eluates that showed a stronger reaction with e-positive than with e-negative or Rhnull RBC, but only in the presence of ex vivo antigen (ie, urine containing the drug and all its metabolites); and an IgM antibody in the serum and initially also on the patient's RBC that, in the presence of ex vivo antigen as well as in the presence of known metabolites of the drug, agglutinated all RBC equally strongly, but was hemolytically more active against E-positive than E-negative cells. Within a few days of stopping the drug the hemolysis rapidly resolved without administration of prednisone, the DAT became negative with anti-IgG and anti-IgM, and the drug-independent anti-E disappeared, but both metabolite-dependent antibodies remained detectable in the patient's serum. We conclude that the production and specificity of the causative antibodies in this case were controlled by a larger antigenic site, presumably consisting of the drug and/or its metabolites plus RBC antigens, rather than by epitopes of the drug or metabolites alone. PMID- 3096401 TI - Human gamma interferon enhances release from phytohemagglutinin-stimulated T4+ lymphocytes of activities that stimulate colony formation by granulocyte macrophage, erythroid, and multipotential progenitor cells. AB - Human gamma interferon (HuIFN gamma) was evaluated for its effects on the release from human peripheral blood T lymphocytes (greater than 98% pure) stimulated by phytohemagglutinin (PHA) of activities that can stimulate granulocyte-macrophage (CFU-GM) colonies and clusters, erythroid (BFU-E) bursts, and mixed (CFU-GEMM) colonies. T lymphocytes did not release these activities in the absence of PHA with or without HuIFN gamma. In the presence of PHA, pure natural HuIFN gamma at concentrations of 0.1 to 100 U/mL significantly enhanced release of these colony stimulating activities. Although enhanced release of granulocyte-macrophage colony-stimulating activities were noted when T lymphocytes were added to the conditioning medium in the presence of 0.1%, 0.5%, and 1% PHA, enhanced release of burst-promoting and mixed colony activities was seen only in the presence of 0.1% and 0.5% PHA. The enhanced release of colony-stimulating activities was not due to HuIFN gamma-suppression of the release from PHA-stimulated T lymphocytes of suppressor molecules. The enhancing effects of natural HuIFN gamma were neutralized with a monoclonal anti-natural HuIFN gamma, and recombinant HuIFN gamma mimicked the enhancing effects of the natural HuIFN gamma. This enhancing effect was noted only when HuIFN gamma was added with the T lymphocytes and PHA during the first 24 hours of incubation. T lymphocytes were separated into T4+, T8-, T8+, and T4- subsets (greater than 98% pure for the appropriate phenotypes) after incubation with OKT4- and OKT8- monoclonal antibodies and sorting on a fluorescence-activated cell sorter (FACS). All types of colony-stimulating activities were released from each population after stimulation with PHA, but enhanced release of these activities in the presence of HuIFN gamma was only detected with the T4+ or T8- subsets of lymphocytes. It cannot be concluded from these studies whether HuIFN gamma is enhancing the release of one or several types of colony-stimulating activities, but these studies suggest a role for HuIFN gamma and T4+ lymphocyte subsets in the regulation in vitro of the release of colony-stimulating activities. PMID- 3096403 TI - Analysis of neutron radiotherapy treatment complications. AB - A total of 6,345 patients have been entered in the RTOG particle registry since it was opened in 1980. Three hundred thirty of those patients were treated with neutrons alone for head and neck cancers, and 128 were treated with neutrons alone for pelvic cancers. The late normal Tissue Severe Toxicity (life threatening and fatal) rates in the head and neck were 9% for high energy accelerators and 20% for low energy accelerators. The late normal Tissue Severe Toxicity rates in the pelvis were 4% for high energy accelerators and 39% with low energy accelerators. PMID- 3096402 TI - Gonadotropin releasing hormone (GnRH) analogs for the treatment of breast and prostatic carcinoma. AB - 'Superagonist' analogs of GnRH produce a paradoxical inhibition of gonadotropin secretion when given on a long-term basis, and may well produce a more complete 'medical oophorectomy' than antiestrogens in premenopausal breast cancer patients. Here we review the background and pharmacology of these agents, together with the experience of their use with prostate cancer and early trials in breast cancer. Their effectiveness without significant toxicity, together with new biodegradable implants for their easily acceptable long-term administration, suggest that a highly selective medical means of fully inhibiting ovarian estrogen production is now available for more extensive trials in breast cancer patients. PMID- 3096404 TI - Relationship between specific molecular connectivity indices and teratogenicity, carcinogenicity, and mutagenicity of chlorinated benzenes and a biphenyl. PMID- 3096405 TI - [Value of neutrons and high-energy linear transfer irradiation in anticancer therapy: radiobiological characteristics]. PMID- 3096406 TI - Pressure reversal of alphaxalone/alphadolone and methohexitone in tadpoles: evidence for different molecular sites for general anaesthesia. AB - Tadpoles were used to study quantitative interactions between high pressure and two intravenous anaesthetics, alphaxalone/alphadolone and methohexitone. The potencies of the two agents were decreased by high pressure but to different extents. The maximum effect was seen in the pressure range 70-130 atmospheres absolute (ATA). The increases in the normobaric anaesthetizing concentration (ED50) required at 100 ATA were alphaxalone/alphadolone:405 +/- 5 (s.d.)%; methohexitone:658 +/- 80 (s.d.)%. For both alphaxalone/alphadalone and methohexitone, the curves obtained when the increase in ED50 was plotted against increasing pressure showed plateaux at pressures above 70 ATA. These data support the concept of the two intravenous drugs causing general anaesthesia by the occupation of separate molecular 'sites' with different but finite capacities. PMID- 3096407 TI - Pharmacological modulation of the effects of N-formyl-L-methionyl-L-leucyl-L phenylalanine in guinea-pigs: involvement of the arachidonic acid cascade. AB - The intravenous administration of the chemotactic and secretagogue peptide N formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 0.3-30 micrograms kg-1) to the guinea-pig induces bronchoconstriction and dose-dependent leukopenia accompanied by mild thrombocytopenia. No electron microscopic evidence of platelet aggregation in lungs or significant accumulation of 111In-labelled platelets in the thoracic region at the height of bronchoconstriction was noted. Bronchoconstriction and leukopenia induced by FMLP were not affected by prostacyclin, by platelet depletion, by the platelet-activating factor (Paf acether) antagonist BN 52021 or by the histamine H1-antagonist mepyramine. Bronchoconstriction, but not leukopenia, was inhibited by aspirin, whereas the peptido-leukotriene antagonist compound FPL 55712 and the cyclo-oxygenase lipoxygenase inhibitor indomethacin reduced bronchoconstriction to a limited extent only. The mixed cyclo-oxygenase/lipoxygenase inhibitor compound BW 755C was very effective in blocking bronchoconstriction by the highest dose of FMLP used, but failed to interfere with leukopenia. FMLP-induced dose-dependent contraction of parenchymal lung strips was accompanied by the formation of immuno reactive thromboxane B2 in amounts markedly less than those formed from exogenous arachidonic acid at concentrations equieffective in inducing contractions. FMLP induced contractions of the guinea-pig lung strip were not modified by mepyramine nor by FPL 55712. They were reduced by indomethacin and aspirin and an even greater reduction was obtained with aspirin used in combination with FPL 55712. BW 755C suppressed the effects of all the concentrations of FMLP tested, whereas tert-butyloxy-carbonyl-L-methionyl-L-leucyl-L-phenylalanine, a chemical analogue of FMLP, displaced the concentration-response curve to the right, without reducing the maximal contraction obtained. The present results indicate that: (a) bronchoconstriction by FMLP is not due to platelet activation, to cyclo-oxygenase dependent mechanisms or to peptido-leukotriene formation. The inhibitory effect of aspirin and BW 755C involves a property other than cyclo-oxygenase inhibition, which is not shared by indomethacin. (b) The contractile effects of FMLP on parenchymal lung strips follow an interaction with specific receptor sites, as shown by the effectiveness of tert-butyloxy-carbonyl-L-methionyl-L-leucyl-L phenylalanine, and involves the combined effects of cyclo-oxygenase and lipoxygenase metabolites. PMID- 3096408 TI - Effects of inhibitors of arachidonic acid metabolism on Paf-induced gastric mucosal necrosis and haemoconcentration. AB - The effects of several inhibitors of arachidonic acid metabolism on gastric necrosis, hypotension, haemoconcentration, leukopenia and plasma exudation induced by platelet-activating factor (Paf) were studied in the rat. A 10 min intravenous infusion of Paf (100 ng kg-1 min-1) caused extensive gastric damage and a marked fall in systemic blood pressure which had not recovered to basal levels 30 min after the infusion had been terminated. Paf also caused significant haemoconcentration, plasma exudation and transient leukopenia. Pretreatment with dexamethasone (0.2 or 2 mg kg-1 s.c.) or prednisolone (20 mg kg-1 s.c.) two hours before Paf significantly reduced the gastric damage and accelerated the recovery of blood pressure after the Paf infusion. Likewise, BW755C (50 mg kg-1 p.o.) significantly reduced the gastric damage. Acute pretreatment with dexamethasone (2 mg kg-1 i.v.) 15 min before Paf, or with indomethacin (5 mg kg-1 s.c.), acetylsalicylic acid (10 mg kg-1 i.v.) or 1-benzylimidazole (50 mg kg-1 s.c.) did not significantly affect the gastric damage induced by Paf. The Paf-induced haemoconcentration and plasma exudation were significantly reduced by pretreatment with prednisolone (20 mg kg-1 s.c.) or BW755C (50 mg kg-1 p.o.), while Paf-induced leukopenia was unaffected by either drug. These studies indicate that cyclo-oxygenase products of arachidonic acid are unlikely to contribute significantly to the gastric damage or the prolonged hypotension induced by Paf. The ability of corticosteroids and BW755C to reduce the gastric damage, haemoconcentration and plasma exudation suggests that lipoxygenase products of arachidonic acid may contribute to these actions of Paf. PMID- 3096409 TI - The inflammatory response of rabbit skin to topical arachidonic acid and its pharmacological modulation. AB - The inflammatory reaction induced by the intradermal injection of arachidonic acid into the rabbit dermis has been investigated. Plasma extravasation was measured by the leakage of 125I-albumin into the tissues and polymorphonuclear leukocyte (PMNL) accumulation was assessed histologically. Arachidonic, 5,8,11,14,17-eicosapentaenoic and 8,11,14-eicosatrienoic acids, but not oleic, linoleic or linolenic acids, caused a concentration-related plasma extravasation following their intra-dermal injection. The plasma extravasation induced by arachidonic acid was dependent on PMNLs. PMNL infiltration and plasma extravasation into arachidonic acid-injected skin sites was inhibited by the mixed cyclo-oxygenase-lipoxygenase inhibitor, BW755C. Arachidonic acid-induced plasma extravasation was inhibited by cyclo-oxygenase and 5-lipoxygenase inhibitors but not by the Paf antagonist, kadsurenone. The inflammation induced by arachidonic acid in the rabbit dermis may be a useful model for evaluating 5 lipoxygenase inhibitors which could be potentially useful anti-inflammatory agents for the treatment of psoriasis and other inflammatory diseases. PMID- 3096410 TI - Deficits of chronic schizophrenia in relation to long-term hospitalization. AB - Eighty chronic schizophrenic and 16 manic-depressive psychotic patients conforming to Research Diagnostic Criteria were examined in terms of their mental state, cognitive functioning, current behaviour, and neurological status. They comprised out-patients, day-care patients, and long-stay in-patients belonging to two mental hospitals with different social conditions. Assessed deficits were not significantly related to record variables such as age, duration of illness, duration of hospitalisation, or treatment received. Analysis of the different groups of patients reveals that long-term hospital care has had little effect on the deficits of chronic schizophrenia, and suggests that these are integral features of the disease process. PMID- 3096411 TI - Respiratory control in the treatment of panic attacks: replication and extension with concurrent measurement of behaviour and pCO2. AB - A case series is reported in which nine patients who experienced phobic and/or nonphobic panic attacks were given a cognitive-behavioural treatment based on the supposition that catastrophic interpretations of sensations produced by hyperventilation played an important role in their attacks. Large and rapid reductions in panic attack frequency and questionnaire report of fear were observed. Patients' resting pCO2 was significantly lower than controls and rose to normal levels during treatment. PMID- 3096412 TI - Manic-depressive psychosis in a mentally handicapped person: diagnosis and management. AB - The diagnosis of manic-depressive psychosis in mentally handicapped people can be easily overlooked, partly because its presentation differs from that in people with normal intelligence. This report illustrates some of the difficulties involved in making the diagnosis of manic-depressive psychosis in a mentally handicapped person and in planning for her future care. PMID- 3096413 TI - Prolactin response induced by ECT and TRH. AB - The prolactin response after ECT in ten female melancholic patients correlated significantly to their prolactin response to i.v. TRH. These findings may suggest an underlying common mechanism between TRH and ECT regarding their PRL releasing properties. PMID- 3096414 TI - Lithium augmentation in the treatment of delusional depression. AB - Five patients suffering with delusional depression, and who were resistant to tricyclic antidepressants, were successfully treated with lithium carbonate. Delusional depression does not usually respond to tricyclic antidepressants, and ECT has been considered the treatment of choice. Such patients often refuse to acknowledge that they are ill. They, therefore, understandably often refuse to accept ECT. In order to treat, the Mental Health Act 1983 must be invoked. Treatment with lithium carbonate is more acceptable to most patients, and in the cases described, patients agreed to take this drug whereas they had refused to accept ECT. PMID- 3096416 TI - Deficits of chronic schizophrenia in relation to long term hospitalization. PMID- 3096415 TI - Lithium carbonate and piroxicam. PMID- 3096417 TI - Cell surface antigen in bilharzial bladder tumours. AB - Detection of the ABO (H) blood group in the urothelium in cases of transitional cell carcinoma of the bladder is a good indicator of the future behaviour of these tumours. Since conventional histopathological and clinical examination in bilharzial bladder carcinoma shows a clinical staging error rate of 37.2%, we used the specific red cell adherence (SRCA) technique to study the cell surface antigens in 28 patients over a 5-year period. A prediction rate of 63.6 to 84.6% was obtained when correlated with clinical behaviour. PMID- 3096418 TI - A single plasma sample method to assess disease activity in patients with bone metastases from carcinoma of the prostate. AB - A single blood sample method was used to measure total skeletal activity during routine radionuclide bone scans in 114 patients with known carcinoma of the prostate. The method is based on the measurement of radioactivity in plasma after administration of 99mTc MDP and 51Cr EDTA, providing an assessment of total skeletal activity independent of renal function. The results showed a significant elevation of skeletal activity in patients with untreated bone metastases when compared with patients with no metastatic spread. Significant elevation with increasing extent of metastases was also shown, the highest activity being in patients with diffuse metastatic spread (superscan). Patients with treated metastatic disease showed significantly lower skeletal activity than patients with untreated bone metastases. The method requires the use of two radiopharmaceuticals injected as a mixture and potential errors may arise from pharmaceutical instability. In addition, elevation of total skeletal activity may be caused by coexistent metabolic bone disease. The results suggest that the measure may provide quantitative information in the assessment of the activity of bone metastases from prostatic carcinoma. PMID- 3096419 TI - The functional value of collateral testicular vascularisation. An experimental study. AB - The functional value of the collateral testicular vascularisation has been studied in the rat. In some cases the spermatic artery was sectioned at different levels and in others the vasal artery was sectioned. Hormonal, pathological and anatomical parameters were investigated. The results support the concept that the vasal artery is the most important collateral artery and that the cremasteric artery plays little, if any, part. They also support the view that following proximal section of the testicular artery, the collateral testicular blood supply is variable and the effects of this division are unpredictable and inconsistent. PMID- 3096420 TI - Biosynthetic growth hormone: whom to treat? PMID- 3096421 TI - A better way to detect growth failure. PMID- 3096422 TI - Acquired cystic disease of the kidney: serious or irrelevant? PMID- 3096423 TI - Easeful death. PMID- 3096424 TI - Use of the general health questionnaire in clinical work. PMID- 3096425 TI - Subnutrition in the elderly. PMID- 3096426 TI - Reviving the Commonwealth Medical Association. PMID- 3096427 TI - Hypogonadism in chronic liver disease: impaired release of luteinising hormone. AB - Alcohol abuse leads to impotence, infertility, and feminisation. Patients with chronic alcoholism may have impaired hypothalamic-pituitary function. The release of luteinising hormone was investigated in men with alcoholic cirrhosis with and without hypogonadism and controls. Blood was sampled every 15 minutes for six or eight hours and luteinising hormone concentrations measured by radioimmunoassay. Data were analysed by iterative computerised analysis and spectral analysis to assess pulsatile release and the length of the cycle, respectively. Pulsatile release of luteinising hormone was shown in all the control subjects; in the men with alcoholic liver disease it was normal in those with subclinical primary testicular failure but absent or grossly attenuated in those with overt combined central and primary gonadal failure. The impaired release of luteinising hormone in the men with overt gonadal failure might be due to a hypothalamic defect. PMID- 3096428 TI - Isolation of Mycobacterium avium-intracellulare-scrofulaceum complex from faeces of patients with AIDS. AB - Thirty faecal specimens from 22 patients with the acquired immune deficiency syndrome were examined by microscopy after Ziehl-Neelsen staining and by culture after decontamination with sodium hydroxide. Thirteen specimens (from 11 patients) were positive for Mycobacterium avium-intracellulare-scrofulaceum on culture, and only five of these on Ziehl-Neelsen staining. Five of the 11 patients had evidence of disseminated infection. Lipid analysis showed six of the nine strains tested to be indistinguishable. These findings support the theory that the gastrointestinal tract is a portal of entry for the organism. PMID- 3096430 TI - Hip fractures in healthy patients: operative delay versus prognosis. AB - One hundred and forty five women who had undergone hemiarthroplasty for a subcapital fracture of the femoral neck but who were otherwise fit were studied to determine whether undue delay between injury and operation influenced their social circumstances three months after surgery. The median delay for those patients who showed good rehabilitation at three months was 29 hours, but for those who showed poor rehabilitation it was 57 hours. This difference was significant. It is suggested that a subcapital fracture in an otherwise fit elderly patient should therefore be regarded as a surgical emergency. PMID- 3096429 TI - Effect of near normoglycaemia for two years on progression of early diabetic retinopathy, nephropathy, and neuropathy: the Oslo study. AB - Forty five insulin dependent diabetics were randomised to treatment with continuous subcutaneous insulin infusion (CSII), multiple insulin injections (five or six daily), or conventional twice daily insulin injections. Near normoglycaemia was obtained with CSII and multiple injections but not with conventional treatment (p less than 0.01). Hypoglycaemic coma was observed less frequently with CSII than with multiple injections and conventional treatment (p less than 0.001), but blood glucose concentrations below 2.5 mmol/l (45 mg/100 ml) were more common. After two years fewer retinal microaneurysms and haemorrhages had developed in the patients given CSII and multiple injections compared with those given conventional treatment, in whom the number had increased significantly (p less than 0.01). Motor nerve conduction velocity deteriorated in the patients given conventional treatment; in those given CSII it was unchanged during the first year but had improved after two years (p less than 0.01). Glomerular hyperfiltration was reduced with CSII, but no change occurred in urine albumin excretion rates. Long term near normoglycaemia may prevent the progression of early stages of late diabetic complications. PMID- 3096431 TI - Trial of early nifedipine in acute myocardial infarction: the Trent study. AB - Over 30 months 9292 consecutive patients admitted to nine coronary care units with suspected myocardial infarction were considered for admission to a randomised double blind study comparing the effect on mortality of nifedipine 10 mg four times a day with that of placebo. Among the 4801 patients excluded from the study the overall one month fatality rate was 18.2% and the one month fatality rate in those with definite myocardial infarction 26.8%. A total of 4491 patients fulfilled the entry criteria and were randomly allocated to nifedipine or placebo immediately after assessment in the coronary care unit. Roughly 64% of patients in both treatment groups sustained an acute myocardial infarction. The overall one month fatality rates were 6.3% in the placebo treated group and 6.7% in the nifedipine treated group. Most of the deaths occurred in patients with an in hospital diagnosis of myocardial infarction, and their one month fatality rates were 9.3% for the placebo group and 10.2% for the nifedipine group. These differences were not statistically significant. Subgroup analysis also did not suggest any particular group of patients with suspected acute myocardial infarction who might benefit from early nifedipine treatment in the dose studied. PMID- 3096432 TI - Arthritis and HLA-B27 in Papua New Guinea. PMID- 3096433 TI - Acquired cystic disease of the kidney: an indication for renal transplantation? PMID- 3096434 TI - Severe illness associated with appearance of antibody to human immunodeficiency virus in an African. PMID- 3096435 TI - Transient ascites in progressive systemic sclerosis. PMID- 3096436 TI - Attitudes to and knowledge about the acquired immune deficiency syndrome: lack of a correlation. PMID- 3096437 TI - In aid of doctors suffering from complaints about AIDS. PMID- 3096438 TI - Medical facilities used by heroin users. AB - There is little information about the extent of contact between heroin users and medical facilities. In this study of heroin users from general practice we found an increase in the attendance of patients after the onset of heroin use and that a high proportion of appointments were made at general practices compared with hospital departments. PMID- 3096439 TI - Does breathing other people's tobacco smoke cause lung cancer? AB - The available epidemiological studies of lung cancer and exposure to other people's tobacco smoke, in which exposure was assessed by whether or not a person classified as a non-smoker lived with a smoker, were identified and the results combined. There were 10 case-control studies and three prospective studies. Overall, there was a highly significant 35% increase in the risk of lung cancer among non-smokers living with smokers compared with non-smokers living with non smokers (relative risk 1.35, 95% confidence interval 1.19 to 1.54). Part of this increase was almost certainly caused by the misclassification of some smokers as non-smokers. As smokers, who are more likely to get lung cancer than non-smokers, tend to live with smokers this misclassification probably exaggerated the estimated increase in risk. Adjustment for this error reduced the estimate to 30% (relative risk 1.30), but as people who live with non-smokers may still be exposed to other people's smoke this estimate was revised again to allow for the fact that a truly unexposed reference group was not used. The increase in risk among non-smokers living with smokers compared with a completely unexposed group was thus estimated as 53% (relative risk of 1.53). This analysis, and the fact that non-smokers breathe environmental tobacco smoke, which contains carcinogens, into their lungs and that the generally accepted view is that there is no safe threshold for the effect of carcinogens, leads to the conclusion that breathing other people's tobacco smoke is a cause of lung cancer. About a third of the cases of lung cancer in non-smokers who live with smokers, and about a quarter of the cases in non-smokers in general, may be attributed to such exposure. PMID- 3096440 TI - Working abroad: stresses and solutions. PMID- 3096441 TI - Pelvic inflammatory disease. PMID- 3096442 TI - Recurring meningitis: beware the normal looking ear. PMID- 3096443 TI - Neurological and neurosurgical approaches in the management of malignant brain tumours. PMID- 3096444 TI - Availability of organs for transplantation. PMID- 3096445 TI - Whooping cough immunisation for children with cerebral irritation or damage in the neonatal period. PMID- 3096446 TI - Respiratory symptoms and bronchial reactivity. PMID- 3096447 TI - Serum concentrations of sex hormone binding globulin in lung cancer. PMID- 3096448 TI - Sleepwalking as a symptom of bulimia. PMID- 3096449 TI - Asthma and climatic conditions: experience from Bermuda. PMID- 3096450 TI - Angina pectoris-like pain provoked by intravenous infusion of adenosine. PMID- 3096451 TI - Halothane and the liver. PMID- 3096452 TI - Plasminogen activators in human colorectal neoplasia. PMID- 3096453 TI - "Near miss" sudden infant death and episodic hypothermia. PMID- 3096454 TI - Career prospects in general surgery in England and Wales. PMID- 3096456 TI - Lassa fever. PMID- 3096455 TI - Hysteria: a case for conservation? PMID- 3096457 TI - Our diurnal nature. PMID- 3096458 TI - AIDS and the condom. PMID- 3096459 TI - AIDS, them, and us. PMID- 3096460 TI - Effect of night and day on preterm infants in a newborn nursery: randomised trial. AB - The effect of alternating night and day on sleep, feeding, and weight gain in 41 healthy preterm infants was examined in a randomised controlled trial. Twenty infants from a night and day nursery, where the intensity of light and noise was reduced between 7 pm and 7 am, spent longer sleeping and less time feeding and gained more weight than 21 infants from a control nursery, where the intensity of light and noise was not reduced. Differences were significant and became apparent only after discharge home; they were still present three months after the expected date of delivery, when infants from the night and day nursery were an average of 0.5 kg heavier (p less than 0.02). These findings suggest that physical environment has an effect (either direct or indirect) on the subsequent behaviour of preterm infants and that exposure to night and day is beneficial. PMID- 3096461 TI - Childhood respiratory infection and adult chronic bronchitis in England and Wales. AB - The high mortality from chronic bronchitis in England and Wales and the excess of urban over rural mortality are unexplained. On dividing England and Wales into 212 local authority areas a strong geographical relation was found between death rates from chronic bronchitis and emphysema in 1959-78 and infant mortality from bronchitis and pneumonia during 1921-5. It was concluded that this relation provided strong evidence of a direct casual link between acute lower respiratory infection in early childhood and chronic bronchitis in adult life. Regression analysis suggested that infection in early childhood had a greater influence than cigarette smoking in determining the geographical distribution of chronic bronchitis. National time trends reflected the influence of both factors. Chronic air pollution in adult life may be less important a cause of chronic bronchitis than previously supposed. PMID- 3096462 TI - Remission of diarrhoea due to cryptosporidiosis in an immunodeficient child treated with hyperimmune bovine colostrum. AB - A boy aged 6 months who presented with poor weight gain, diarrhoea, and infection with Pneumocystis carinii was found to have congenital hypogammaglobulinaemia, which did not improve despite monthly treatment with intravenous gammaglobulin. At the age of 3 years and 2 months he developed severe vomiting and diarrhoea due to cryptosporidiosis, which failed to respond to conventional treatment. Infusion of hyperimmune bovine colostrum produced against parasite antigen, given by nasogastric tube, was started after symptoms had persisted for three weeks. His vomiting and diarrhoea resolved within five days of treatment, and oocysts were no longer seen in the stools after eight days. Later, however, he developed a rare complication, and oocysts were found in the common bile duct. Hyperimmune bovine colostrum may be useful in the treatment of many patients with immunodeficiency disorders. PMID- 3096463 TI - Paradoxical gas embolism in a scuba diver with an atrial septal defect. PMID- 3096464 TI - Hyperparathyroidism associated with severe hypercalcaemia and myocardial calcification despite minimal bone disease. PMID- 3096465 TI - Can patients benefit from reading copies of their doctors' letters about them? PMID- 3096466 TI - Pustular dermatosis induced by co-trimoxazole. PMID- 3096467 TI - Blood cotinine, carboxyhaemoglobin, and thiocyanate concentrations and cigarette consumption. PMID- 3096468 TI - Attitudes of doctors to the Alma Ata recommendations in Sri Lanka. AB - A detailed postal questionnaire was sent to 400 general practitioners, hospital doctors, and Ayurvedic practitioners in Sri Lanka as part of a wider study to investigate the delivery of primary medical care. The responses to questions that were related to the Alma Ata recommendations, which aim at providing "health for all by the year 2000," and the perceived health needs of the population are reported. Basic sanitation, clean water, adequate nutrition, and improved health education were considered to be the most important needs. When asked to suggest one change in health care 30% of the doctors recommended the integration of primary and secondary care services. PMID- 3096469 TI - Study of "discharge communications" from hospital. AB - All hospital discharge communications concerned with acute admission from one general practice over a three month period were analysed. There was an appreciable delay between the time that the patient was discharged and the information was received by the general practitioner. Just over half of the patients had contacted their general practitioner after discharge before the general practitioner had received any information. The content of the communications was variable, and important subjects were frequently omitted. No communication was received for 11% of the discharged patients. There is a need for more efficient communication between secondary and primary care. PMID- 3096470 TI - Deaths of two hospital inpatients poisoned by pilocarpine. AB - Two inpatients of one hospital ward died. Pilocarpine poisoning was suspected and subsequently confirmed by analysis of urine. The circumstantial evidence strongly suggested that the food given to the patients in the ward had been adulterated. Police inquiries failed to elicit any further information, and open verdicts were returned at the inquest. Precautions taken subsequently to prevent a similar event--sealing food containers and trolleys--entailed a capital cost of 43,000 pounds. In addition, food stores were kept locked and tighter control kept on drugs stored in ward pharmacies. PMID- 3096472 TI - Premenstrual syndrome. PMID- 3096471 TI - Dangerous misuse of sulphonylureas. PMID- 3096473 TI - Disclosure of medical records in litigation. PMID- 3096474 TI - Assessment of non-mydriatic fundus photography in detection of diabetic retinopathy. PMID- 3096475 TI - Computer aided diagnosis of acute abdominal pain. PMID- 3096476 TI - Trace element analysis of hair. PMID- 3096477 TI - Use of serum cotinine to assess the accuracy of self reported non-smoking. PMID- 3096478 TI - Private nursing homes: contribution to long term care of the elderly. PMID- 3096479 TI - Platelet function defects in chronic alcoholism. PMID- 3096480 TI - Exposure of midwives to nitrous oxide. PMID- 3096481 TI - Munchausen's syndrome by proxy. PMID- 3096482 TI - Origin of AIDS. PMID- 3096483 TI - Opportunistic screening for cervical cancer. PMID- 3096485 TI - Ultrasound screening for hip abnormalities. PMID- 3096484 TI - Stress hyperglycemia in non-diabetic patients with myocardial infarction. PMID- 3096486 TI - Contribution of inappropriate treatment for hypertension to pathogenesis of stroke in the elderly. PMID- 3096487 TI - Detection of patients with high alcohol intake by general practitioners. PMID- 3096488 TI - Sensory effects in man of lesions of the posterior columns and of some other afferent pathways. AB - Clinical observations are presented on the sensory effects of lesions of different afferent pathways of the spinal cord, correlated whenever possible with histological evidence of the location and extent of the lesions. They are based on personal cases and on significant cases in the literature, including posterior column section, other causes of damage to the posterior columns, and cases of commissural myelotomy. It is concluded that the traditional view of the effects of lesions of the posterior columns is correct, but that evidence from cases proved by postmortem examination is still needed. When the information normally supplied by the posterior columns is cut off, primary sensibility for light touch and pressure is not lost, but any kind of discrimination is disturbed. There is also a disturbance in knowledge of movement and position, ataxia, and clumsiness in the use of the hands. These defects greatly affect the palpatory examination of objects and, although they may appear slight on routine neurological examination, they can cause severe disturbances in the activities of daily living. For tactile modalities, a lesion of the spinothalamic complex causes minimal or no defects and a lesion of the posterior columns causes only slight defects, whereas a lesion of both pathways gives rise to total loss of tactile and pressure sensibility in the part of the body served by both pathways. This conclusion is based on 2 cases with combined commissural myelotomy and anterolateral cordotomy. The following disturbances of mechanoreception attributed to lesions of the posterior columns are discussed: lability of threshold, persistence of sensation, tactile and postural hallucinations and temporal and spatial disturbances. In man, lesions of the posterior columns cause an increase in pain, tickle, warmth and cold. Cases are presented with and without lesions of the posterolateral columns in conjunction with lesions of one or both anterolateral columns. As these lesions did not affect sensation and as there was no difference in the sensory state following anterolateral cordotomies with or without involvement of the posterolateral column, it is concluded that lesions of this column have no effect on sensation. Cases with lesions of the anterior two-thirds of the cord are also presented to illustrate the sensory state with only the posterior third of the cord intact. In these cases, tactile and pressure sensibility and knowledge of movement and position are normal. PMID- 3096489 TI - A thyrotropin-releasing hormone-containing system in the rat dorsal horn separate from serotonin. AB - In this study, we report the identification of a thyrotropin-releasing hormone (TRH)-containing system in the dorsal horn of the rat spinal cord. This system is distinct from the TRH and serotonin (5-hydroxytryptamine, 5-HT) cotransmitter supraspinal system that has projections to the intermediolateral (IML) and ventral columns. Spinal cord sections from untreated rats, and those treated with colchicine or 5,7-dihydroxytryptamine (5,7-DHT) were processed using peroxidase antiperoxidase (PAP) immunocytochemistry with nickel intensification. Results of the 5,7-DHT treatment were verified by quantifying TRH and 5-HT by radioimmunoassay (RIA) and high performance liquid chromatography (HPLC), respectively. Prominent immunocytochemical staining for TRH in the dorsal horn was seen in varicose fibers mainly in lamina II and superficial lamina III of the dorsal horn of the spinal cord of control rats. A few fibers were seen ascending into lamina I. A moderate number of fibers that were immunoreactive for 5-HT were primarily in laminae I and II. The distribution of TRH- and 5-HT-containing neurites in the IML and the ventral horn agreed with previously published reports. Rats treated with colchicine showed many small round TRH immunoreactive cells that were limited to laminae II/III of the dorsal horn. TRH immunoreactivity in the dorsal horn and IML was resistant to the effects of the selective serotonin neurotoxin, 5,7-DHT, while the ventral horn was depleted of TRH staining. Serotonin was almost completely eliminated in all spinal cord laminae. Quantitative biochemical studies showed significant, but non-parallel reductions of TRH and 5-HT in cervical, thoracic and lumbar spinal cord. These studies demonstrate the existence of TRH-containing cell bodies and terminals in the dorsal horn of the rat spinal cord. These findings provide evidence that a TRH-containing system exists in the dorsal horn of the rat and that it is distinct from the descending medullary raphe system that contains 5-HT; suggest that a population of TRH-containing fibers that project to the IML may not contain 5-HT; and confirm previously published results that 5-HT and TRH coexist in terminals in the ventral horn of the spinal cord. PMID- 3096490 TI - Presence of synapsin I in afferent and efferent nerve endings of vestibular sensory epithelia. AB - The presence and localization of synapsin I were investigated in the cat vestibular epithelium, using a rabbit anti-synapsin I antibody. The staining was performed by immunofluorescence or by a peroxidase-anti-peroxidase technique. A strong immunoreactivity was observed with both methods. It appeared as spherical patches distributed in the lower part of the epithelium. This distribution pattern is very similar to that of the efferent synaptic endings which are filled with microvesicles. Elongated immunoreactive segments were also observed around some hair cells. They suggest the presence of synapsin I in the afferent sensory endings contacting the hair cells. This immunoreactivity occurs in early postnatal and adult stages. PMID- 3096491 TI - Calcium influxes into brain and cerebrospinal fluid are linearly related to plasma ionized calcium concentration. AB - Unidirectional Ca influxes into brain and cerebrospinal fluid (CSF) were measured at different plasma concentrations of ionized Ca ([Ca]i) in pentobarbital anesthetized rats. Plasma [Ca]i was varied acutely from 0.6 to 3.0 mumol/ml by intravenous infusion of EGTA, NaCl or CaCl2 or by thyroparathyroidectomy. Ca influx was determined from the 15-min uptake of 45Ca after intravenous injection. There were significant regional differences in 45Ca uptake into the CNS, with a approximately 20-fold greater rate into ventricular CSF than into frontal cortex. Autoradiographs of 45Ca uptake demonstrated that uptake into frontal cortex reflects primarily transport across the cerebral capillaries, whereas uptake into ventricular CSF reflects transport across the choroid plexuses. At both sites, Ca influx was a linear function of plasma [Ca]i and extrapolated to zero at [Ca]i = 0. Infusion of EGTA or CaCl2 did not alter the integrity of the blood-brain barrier, as determined by the permeability to [14C]sucrose. These results indicate that Ca influx into the CNS is not regulated by a saturable mechanism that is sensitive to acute changes in plasma [Ca]i. The proportionality between influx and concentration is suggestive of passive diffusional transport. The brain is protected from acute changes in plasma [Ca]i by the low cerebrovascular permeability to Ca, approximately 5 X 10(-8) cm/s. PMID- 3096492 TI - Sequestration of tubulin in neurons in Alzheimer's disease. AB - In Alzheimer's disease (AD), a variety of populations of neurons exhibits cytoskeletal abnormalities, including neurofibrillary tangles (NFT) in perikarya, Hirano bodies in dendrites and filament-distended axons/terminals/dendrites (neurites) in senile plaques. Some nerve cells, particularly pyramidal neurons of the hippocampus, also develop Hirano bodies (paracrystalline arrays of actin) and granulovacuolar degeneration (GVD; granular inclusions in cytoplasmic vacuoles). Since abnormalities of cytoskeletal elements have been implicated in the formation of NFT, neurites and Hirano bodies, the present study was designed to determine whether GVD also may represent a type of cytoskeletal pathology. Sections of hippocampus from controls and from individuals with AD were stained by immunocytochemical methods using monoclonal and polyclonal antibodies directed against a variety of cytoskeletal antigens. Granules of GVD contained tubulin like immunoreactivity and absorption with purified tubulin abolished staining. Other antigens were not demonstrated in granules when antibodies directed against other cytoskeletal antigens were used. The observation of sequestration of tubulin in granules is consistent with the concept that abnormalities of the neuronal cytoskeleton are an important part of the cellular pathology of AD. PMID- 3096493 TI - Effect of hallucinogens on spontaneous and sensory-evoked locus coeruleus unit activity in the rat: reversal by selective 5-HT2 antagonists. AB - As previously reported, systemic administration of the hallucinogens D-lysergic acid diethylamide (LSD) (5-10 micrograms/kg) and mescaline (2 mg/kg) in the anesthetized rat produced a decrease in spontaneous activity but, paradoxically, facilitated activation of locus coeruleus (LC) neurons by sciatic nerve stimulation. In the present study, the hallucinogen 2,5-dimethoxy-4 methylamphetamine (DOM) (20-80 micrograms/kg) was found to have similar effects. Systemic administration of the selective 5-HT2 antagonists LY 53857 (0.02-0.8 mg/kg) and ritanserin (0.1-0.3 mg/kg) completely reversed both actions of the hallucinogens on the LC. In contrast, LY 53857 did not reverse the effects of (+) amphetamine (0.5 mg/kg) on the spontaneous or sensory-evoked activity of the LC. These results suggest that the common actions of indoleamine and phenethylamine hallucinogens displayed in the LC are mediated via 5-HT2 receptors; however, these receptors appear to be located outside the LC itself. PMID- 3096494 TI - The role of the nucleus raphe pontis and the caudate nucleus in alfentanil rigidity in the rat. AB - Attempts to eliminate or reduce the rigidity induced with high-dose narcotic anesthesia in the operating room have been only partially successful. Previous investigations of opioid receptor sites mediating this rigidity have implicated two central regions: the nucleus raphe pontis (NRP) within the reticular formation and the caudate nucleus (CN) within the basal ganglia. The present study used systemically administered alfentanil (ALF), a potent, short-acting fentanyl analog, and intracerebrally infused methylnaloxonium (MN), a quaternary derivative of naloxone, to elucidate further the functional role of the NRP and CN in rigidity. ALF (0.5 mg/kg s.c.) produced a reliable model of rigidity, as documented by gastrocnemius electromyography. The onset of this rigidity was within 60 s of ALF administration, with a total duration of approximately 40-50 min. Intracerebroventricular (i.c.v.) injections of 2.0 or 4.0 micrograms of MN 15 min prior to ALF treatment prevented rigidity, while 0.125 or 0.5 microgram had no significant effect on rigidity. MN injected directly into the NRP at doses as low as 0.125 microgram significantly antagonized ALF-induced rigidity, while injections of MN into the caudate nucleus at doses as high as 4.0 micrograms failed to antagonize ALF-induced rigidity. These observations demonstrate that injection of MN into the NRP is at least 16-fold more effective in blocking ALF induced rigidity than MN injected into the ventricle and, more importantly, at least 32-fold more effective than MN injected into the CN. The results suggest that the NRP may be an important site for the neural control of muscular rigidity associated with high-dose narcotic administration. PMID- 3096495 TI - Descending noradrenergic pathways involved in the A5 depressor response. AB - The objective of the present study was to analyze the anatomical basis of the A5 depressor response and to test if the putative neurotransmitter noradrenaline is involved in the response. Two approaches were used; one was neuroanatomical and the other was pharmacological. First, the retrograde transport method in which two fluorescent markers (Fast blue and rhodamine microspheres) was used in combination with the indirect immunofluorescence technique to establish that A5 catecholamine neurons project to both the spinal cord and the region of the nucleus tractus solitarii (NTS). Second, we analyzed the effects of 6 hydroxydopamine (6-OHDA) lesions of the spinal cord and/or NTS area on the A5 depressor response. This response was elicited by a 80-nl microinjection of L glutamate (500 mM) into the A5 region in pentobarbital anesthetized rats; it was characterized by a decrease in blood pressure and heart rate. After destruction of various noradrenergic terminal fields we have found that intraspinal injections of 6-OHDA caused a 30% reduction in the blood pressure component of the A5 depressor response and a transient depression of the bradycardic response. This result suggests that only a small portion of the A5 depressor response depends on the descending A5 spinal pathway. Injections of 6-OHDA into the NTS region caused a transient depression of the A5 depressor response, and by 7-14 days postinjection, the response returned to normal. After combined 6-OHDA injections into the spinal cord and NTS area, the blood pressure and heart rate components of the A5 depressor response were reduced to 80% of the control level at 3 days postinjection. By 14 days, even with severe depletion of noradrenaline in the spinal cord (96%) and a moderate depletion of noradrenaline in the NTS (50%), the A5 response was restored to about 80% of its original magnitude, suggesting some type of functional recovery occurs in this system. Third, the blood pressure decrease elicited by L-glutamate stimulation of the A5 cell group was unaffected by pharmacological blockade of the heart. In addition, this response appeared to be normal in rats that had both their autonomic supply to the heart blocked pharmacologically and their spinal cord noradrenaline levels depleted (14 days after intraspinal 6-OHDA injections). These data suggest that the major A5 depressor response operates mainly by inhibition of the sympathetic outflow involved in control of total peripheral resistance and that this system is controlled by a descending spinal pathway which probably does not use noradrenaline as a neurotransmitter. PMID- 3096496 TI - Role of ascending and descending noradrenergic pathways in the antinociceptive effect of baclofen and clonidine. AB - Baclofen and clonidine interact with central noradrenaline (NA) pathways by a variety of mechanisms. The specific role of ascending and descending pathways in antinociception produced by these agents was examined by lesioning the dorsal bundle (DB), locus coeruleus (LC) and descending NA pathways by the microinjection of the neurotoxin 6-hydroxydopamine (6-OHDA). Lesions were verified using high-performance liquid chromatography analysis of NA. Both baclofen and clonidine were injected intraperitoneally in all experiments. The antinociceptive effect of baclofen in the tail-flick test was inhibited 7-21 days after DB lesions. This manipulation decreased NA levels in cortex, hippocampus and hypothalamus but did not alter spinal cord levels. Lesions of the LC potentiated the effect of baclofen 12-16 days postlesion. NA levels were reduced in all the regions just mentioned. DB lesions produced a transient decrease in the effect of clonidine, being observed 7 but not 12-16 days postlesion. Neither acute depletion of NA levels with alpha-methyl-p-tyrosine (alpha-MPT), nor LC lesions significantly affected antinociception produced by clonidine. Intraspinal 6-OHDA potentiated the antinociceptive action of clonidine in the tail-flick test. This treatment markedly reduced spinal cord NA levels, but had minimal effects on brain NA. The results of this and previous studies in this laboratory suggest that the antinociceptive effect of baclofen is mediated by interactions with both ascending and descending NA pathways. These pathways appear to interact in a complex manner. Interpretation of data for clonidine is complicated because lesions can both deplete endogenous NA as well as inducing postsynaptic supersensitivity of alpha 2-receptors. Clonidine does not depend on endogenous NA pathways for producing antinociception because acute depletion of NA with alpha MPT does not alter its action. Spinal sites of action are of importance following systemic clonidine because intraspinal 6-OHDA produces supersensitivity. Altering NA activity in ascending pathways alone produces a transient inhibition of the effect of clonidine, but supersensitivity is not apparent. Simultaneous lesions of both ascending and descending pathways do not produce supersensitivity, again suggesting important interactions between such pathways can occur. PMID- 3096497 TI - Ontogeny of spontaneous petit mal-like seizures in Wistar rats. AB - Wistar rats spontaneously presenting electroclinical signs of petit mal-like epileptic seizures were inbred until all offspring were affected, and the ontogeny of this inherited phenotype was studied in the offspring from 30-60 days of age to 18 months. The first EEG spike and wave discharges appeared at 40-120 days. Their number and duration increased progressively with age. PMID- 3096498 TI - Petit mal seizure spikes in olfactory bulb and cortex caused by runaway inhibition after exhaustion of excitation. AB - The olfactory bulb (OB), anterior olfactory nucleus (AON) and prepyriform cortex (PC) maintain 3 kinds of feedback among their populations of excitatory and inhibitory neurons: negative feedback, mutual excitation, and mutual inhibition. At normal levels of synaptic input these are balanced and give rise to chaotic and near-sinusoidal oscillatory EEG activity. Under intense repetitive electrical stimulation of the lateral olfactory tract (LOT), there is failure of the afferent excitatory terminals, perhaps due to transmitter depletion. In this circumstance there is deficient excitatory input under the condition of a high level of sustained activity among mutually inhibitory neurons. An instability develops in which some inhibitory neurons become more disinhibited (excited) and others more inhibited (less active) to the point of a paroxysmal discharge that is manifested in a massive compound IPSP of the excitatory neurons. The paroxysm terminates abruptly, but by mechanisms still unclear repeats at a rate of about 3/s for 10-70 s. It is accompanied by simultaneous ipsilateral twitching of the eyelids and muzzle, salivation, tearing, arrest, and lack of responding to sensory stimuli but without loss of posture, resembling absence in humans. It does not result from runaway mutual excitation, and it rarely culminates in full blown convulsions. Similar spikes usually also occur in the OB and AON; the sequences of spikes appear to entrain. These normal and seizure EEGs are simulated with a network of non-linear differential equations, that is designed in conformance with the anatomy and physiology of the olfactory system. The seizure appears as an emergent property of the OB, AON and PC interactive system, that is due to an induced asymmetry in the feedback network that controls normal background activity. PMID- 3096499 TI - Depletion of striatal beta-phenylethylamine following dopamine but not 5-HT denervation. AB - The effects of lesions of the substantia nigra (electrolytic 2 mA 10 sec, or 6 OHDA 2 or 8 micrograms) and of the midbrain raphe nuclei (electrolytic 2 X 1.0 mA 10 sec) at 7 days postlesion on striatal levels of beta-phenylethylamine, DA, DOPAC, HVA, 5-HT and 5-HIAA and on hypothalamic levels of beta-phenylethylamine, DA, NA, 5-HT and 5-HIAA were investigated. In the presence of deprenyl (2 mg kg-1 2 hr SC), both electrolytic and 6-OHDA-induced dopamine-depleting lesions of the nigra but not 5-HT-depleting lesions of the raphe nuclei resulted in a marked decrease in the accumulation of beta-phenylethylamine. The marked reduction in accumulation of striatal beta-phenylethylamine in response to lesions of the substantia nigra indicates that the intraneuronal compartment is a major site of striatal beta-phenylethylamine synthesis. An equivalent decrease (approximately 40%) in the accumulation of 5-HT was observed following electrolytic lesions of the substantia nigra or raphe nuclei after administration of L-5-HTP (200 mg kg-1 hr IP). As L-5-HTP at the dose employed in this study is taken up non-selectively by both DA- and 5-HT-containing neurones the loss of L-AAD following nigral and raphe lesions was apparently equivalent. These results indicate that depletion of beta-phenylethylamine may not be simply attributable to a general loss of L-AAD following lesions of monoamine-containing neurones and suggest either co localisation of beta-phenylethylamine and DA or the existence of distinct beta phenylethylamine-containing neurones. PMID- 3096500 TI - [Female transmitters of Duchenne's myopathy: detection by quantitative ultrasonography combined with blood creatine kinase]. AB - Duchenne muscular dystrophy (DMD) is a disease inherited in an X-linked recessive manner. Nothing is yet known about the gene defect involved. The problem of DMD carrier detection is very important and now without satisfactory solution. Presently the best method, for this detection, is the determination of the serum creatine-kinase (CK) level. However about 30% of DMD children's mothers have normal CK levels. In this study we associated CK determination and a new echographic method. This physical investigation is based on the muscle attenuation measurements through the evolution of the running spectral moments. The parameter expressed is the slope of the ultrasound attenuation signal (in decibels by centimetre and by megahertz; dB . cm-1 . MHz-1). We measured this parameter in vivo on the vastus medialis. The use of the chemical technique and of the physical one improves largely the detection of obligate carriers of Duchenne muscular dystrophy than when one of these methods is employed alone. One such combination recognizes 17 out of the 19 obligate carriers in our series. The difference of the results obtained by these two unrelated methods cannot be yet interpreted, but can reflect genetic heterogeneity in DMD and the inactivation of the X chromosomes. PMID- 3096501 TI - [Course of the degeneration of the primary visual system in albino quails with glaucoma]. AB - In the quail, a sex-linked albino mutation is associated with buphthalmic glaucoma. This progressive disorder is detectable 3 to 6 months after hatching. Its development leads to a degeneration of retinal projection according to a relatively orderly sequence progressing from the tegmentum to the tectum and from the pretectum to the thalamus. We suggest that the degeneration of visual axons might be produced by mechanical compression resulting from an increase in intraocular pressure. PMID- 3096502 TI - [Long-duration insomnia after lesions of the perikaryons of the paramedian preoptic area in cats]. AB - The destruction of paramedian preoptic neurons by intra-tissue injection of ibotenic acid induces, in the cat, the disappearance of deep slow wave sleep and paradoxical sleep for 2 to 4 weeks, while light slow wave sleep is slightly disturbed. This insomnia, well tolerated, is not secondarily associated with central temperature disturbance. PMID- 3096503 TI - [Biochemical characterization of an immune serum which specifically marks neurons in neurofibrillary degeneration in Alzheimer's disease]. AB - We have raised an antiserum which is labelling specifically neurofibrillary tangles of Alzheimer's disease. We show here that anti-tangles detects on immunoblots exclusively Tau, a set of proteins that promote microtubule assembly. Conversely, an anti Tau detects histologically Alzheimer tangles. Accordingly, neurofibrillary tangles are very likely composed of aggregated Tau proteins, due to an anomaly of microtubular protein synthesis or to a general suffering of certain pyramidal neurons leading to an elective aggregation of Tau. PMID- 3096504 TI - [Stimulation of human lymphocytes by phorbol acetate and a calcium ionophore induces an early transient expression of the c-fos oncogene followed by c-myc]. AB - After stimulation of human lymphocytes by 12-0 tetradecanoyl phorbol acetate (TPA) and by the calcium ionophore A23187 an early transient expression of proto oncogene fos followed by an expression of c-myc is observed, as has been described in rodent fibroblast stimulated by growth factors. This observation suggests a direct role of protein Kinase C and of calcium flux an the induction of cellular oncogenes fos and myc that may be associated with the early steps of activation and proliferation of lymphocytes. PMID- 3096505 TI - [Differential taste sensitivity of Pygmy and non-Pygmy populations of the dense forest, Sudanese and Eskimos, in relation to their biochemical environment]. AB - Significant differences of taste thresholds for different sugars, salt, organic acids, and bitter products, observed in human populations in contrasted environments, are related to potential variations of traditional diet. In this respect, biochemical composition of the environment would be the major selective pressure for taste perception. PMID- 3096506 TI - [Effect of basic FGF on the proliferation of rat neuroblasts in culture]. AB - Cultures highly enriched in neuronal cells, derived from brain hemispheres of 13 day-old rat embryo, were used. In these cultures, neuroblasts proliferate during the first 3 days in vitro. The addition of the astroglial growth factor (AGF2), also known as basic fibroblast growth factor (bFGF), 4 hrs. after seeding, induces a strong increase of [125I]-deoxyuridine incorporation. We checked by autoradiography combined with specific immunocytochemical staining of the neurones, using an anti-neurofilament antibody, that the number of proliferating neuroblasts is increased after the treatment. These results demonstrate that AGF2, or bFGF, is a mitogenic factor for rat neuroblasts in culture. PMID- 3096507 TI - [Non-participation of bulbar inspiratory neurons in the esophago-diaphragmatic inhibitory reflex]. AB - The effects of the distension of the lower oesophageal sphincter were studied on the inspiratory activity of 96 medullary neurons located either in the dorsal or in the ventral respiratory groups and on the inspiratory activity of the costal and crural parts of the diaphragm in barbiturate anaesthetized cat. Inhibition of the inspiratory activity of the crural part of the diaphragm during oesophageal distension was never associated with significant changes of the medullary inspiratory neuron discharge. These results suggest that the observed crural inhibition is due to reflex loop that does not include the inspiratory neurons belonging to the dorsal and the ventral respiratory groups. PMID- 3096508 TI - [Nuclear proteins preferentially bound to the beta-globin gene: cellular specificity and variation during terminal differentiation of mouse erythroblasts]. AB - Restriction fragments of the mouse beta major globin gene and of the long terminal repeat (LTR) DNA fragment of the mouse mammary tumor provirus as a control, were used to analyze the specificity of DNA-protein interactions in nuclear extracts of mouse erythroleukemia (MEL) cells and of other differentiated mouse cultured cell lines. After gel electrophoresis and transfer to nitrocellulose, DNA-binding proteins with a preferential affinity for the cloned beta-globin genomic sequence were characterized and related to the level of globin gene expression during induction of differentiating mouse erythroblasts. Two proteins (110 K and 75 K) appear in differentiated MEL cells while another one (100 K), for which we have localized the binding site on the beta-globin gene, is present only in immature MEL cells. PMID- 3096509 TI - [Comparison of several protein sequences by recognition of conserved regions]. AB - The sequences of related proteins show the alternance of conserved and variable regions. This fact is generally seen as a reverberation of 3 D constraints onto 1 D structures. Although the exact meaning of such constraints remains elusive, conserved regions can be extracted from protein chains and used to align them. We developed a program that efficiently performs this task. The program constructs symbolic motifs fitting a target subsequence present in every chain without requiring any insertion or deletion. However, a motif can be obliterated by substitutions when it is found in a sequence. The motifs formally consist in aminoacid symbols separated (and virtually preceded and followed) by a variable number of wild-card symbols. A wild-card, which can match any aminoacid of the chains (with no increment of score), represents a variable site within conserved regions. Different motifs are progressively built by substituting a wild-card with an aminoacid symbol within or beside preexisting motifs. Only those motifs showing an outstanding association of high matching score over all chains, and of low deviation between extreme scores over individual chains are selected for making the next generation. Starting with a null motif, the construction ends when no new aminoacid can be introduced into the current motifs. A surviving motif is then considered valid if it maps without ambiguity a unique region in every sequence, and the motif with highest score is finally selected. The construction of new motifs is then reinitated for the left and right parts of the sequences, after these have been split by the previously selected motif.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096510 TI - [Characterization of desmin in the electric organ of Electrophorus electricus L]. AB - The intermediate filament protein of the electric organ from the Electrophorus electricus L. was purified in DEAE-cellulose column after extraction with a Triton X-100 buffer and urea solubilization. The desmin was analysed by SDS-PAGE against desmin purified from chicken gizzard. Characterization of desmin from the electric eel was carried out by peptide mapping and immunoblotting methods. PMID- 3096511 TI - [Distortion of the maternal segregation of the silent alleles of complement factor 4 in normal and diabetic families]. AB - 54 normal Caucasian families and 169 families in whom at least one child had type I diabetes (IDDM) were genotyped for HLA-A, B, C, DR and for the complement factors Bf and C4. The paternal and maternal transmission of the different alleles and of haplotypes and complotypes in linkage desequilibrium have been analysed. No distortion of the paternal transmission has been observed in the offspring of the two series of families. On the contrary, a distortion of the maternal segregation of the silent alleles at the complement factor C4A and B locus was found: mothers transmitted C4AQ0 more often than expected to their male offspring (p less than 0.04 in normal families, p less than 0.001 in IDDM families) while they transmitted C4BQ0 in excess to their female offspring (p less than 0.01 and p less than 0.03 in normal and IDDM families, respectively). PMID- 3096512 TI - [Transmission of Vibrio cholerae. Possible role of the camel]. AB - Choleraic vibrio uses the moving means that man discovers to his own use. Camels (passive and active vehicles of large quantity of crude water) were experimentally infected with a Vibrio (tox. +) and an Aeromonas (tox. +). Suckling young camels eliminate them for 6 days and grown-up camels for 25 days. This experience, associated with the discovery of Vibrio non 01 and Shigella in the caravan camel dungs, lead them to become a potential vector of spreading from one oasis to another. PMID- 3096513 TI - [Intravector anti-Plasmodium activity of a pyrethrinoid: deltamethrin]. AB - In vitro tests, deltamethrin reduced the parasitemic index of Plasmodium falciparum on human red blood corpuscles. In vivo tests, at sublethal doses, deltamethrin limited the development of the sporogonic cycle of Plasmodium yoelii yoelii in Anopheles stephensi. This novel type of antiplasmodic activity involve an intravectorial route and gives an explanation about surprising antimalaria effects observed several months after treatment. PMID- 3096514 TI - [LHRH and LH release in the red fox Vulpes vulpes L]. AB - Pituitary responsiveness to exogenous LHRH was studied in vivo and in vitro in the female red fox, a mono-oestrous species. In vivo, the ability of the pituitary to release LH in response to a single injection of LHRH (2 micrograms/kg) was determined at various stages of the reproductive cycle. The greatest responsiveness is observed during the preovulatory period, the lowest during the luteal phase. During the anoestrus phase, the responsiveness is reduced by more than 50% in lactating females compared to non lactating females. In vitro, dispersed fox anterior pituitary cells were exposed four times to LHRH (10(-9) M), hourly, for 8 min. Pituitary cells were taken from lactating and non lactating females. The cells are not sensitive to LHRH in lactating females but become more and more sensitive after weaning. It is suggested the inhibitory influence of lactation could be the result of prolactin-ovarian steroids gonadotrophins interactions. PMID- 3096515 TI - [Somatomedin C: a factor of the differentiation of adrenal cortex cells]. AB - Using a model of bovine adrenocortical cells cultured in a chemically defined medium, we have shown that pure biosynthetic IGF 1/SmC increases adrenal steroidogenic function. The treatment with increasing concentrations of SmC (0 200 ng/ml) increases the AII binding and synergizes the effect of AII on steroidogenesis. The maximal effect is observed with 50 ng/ml SmC for 48 hrs. This effect of SmC could not be attributable to a mitotic effect, since 100 ng/ml of SmC for 48 hrs., induced a very slight increase in DNA synthesis (X 1.2) without any modification of corticoadrenal cell number. Insulin mimics the steroidogenic effect of SmC, but only at high concentrations. The effects of these two hormones are not additive, suggesting a common step in their mechanism of action. In summary, SmC exerts a direct cytodifferentiating effect on adrenal steroidogenesis. PMID- 3096516 TI - [Functional inhibition by cyclosporin A of the lymphocyte receptor for the AIDS virus (HIV)]. AB - The Human Immunodeficiency Virus (HIV) displays a selective tropism for cells expressing the CD4 molecule which, by itself, represents at least part of the specific receptor for this virus. However, modification of the activation state of each individual cell seems critical not only for virus replication but also for its binding and subsequent penetration into its target. We demonstrate here that Cyclosporin-A (CSA), a drug which inhibits IL-2 dependent T-lymphocyte proliferation and differentiation and which is known for its immunosuppressive activity, can prevent subsequent virus binding to cells otherwise susceptible to HIV. Normal T-lymphocytes were preincubated in vitro with CSA at concentrations that were in the same range than those reached in the serum of treated patients. This resulted in the complete disappearance of HIV receptors (HIV-R), as assessed by the direct measure of specific binding of fluoresceinated HIV (HIV-FITC), and in the subsequent inhibition of HIV replication in cultured cells. Moreover CSA pretreatment of IL-2 independent transformed cells derived from the CEM line, before their infection, strongly inhibited HIV adsorption as well as further virus replication. These results provide a new experimental basis for the potential application of CSA in the treatment of HIV-related diseases. PMID- 3096517 TI - [Effect of thyroidectomy on variations during the spring and summer of the testicular activity and blood prolactin in the mink]. AB - The possible role of thyroid hormones in the setting of sexual quiescence was investigated in the mink, since levels of thyroid hormones were earlier shown to rise while testicular activity decreased. When performed at the beginning of the sexual period, thyroidectomy transiently stimulated testosterone production, and significantly prolonged the duration of maximal testicular development. These results indicate that mink conforms to a pattern of inhibitory thyroid-testis interactions similar to that previously described in several species of birds and mammals. Thyroidectomy was unable, however, to prevent ultimately the installation of sexual quiescence which also appears independent of the photoperiod. On the other hand, thyroidectomy did not modify, from February to October, the general pattern of prolactin secretion, even though the vernal stimulation of prolactin secretion, induced by increasing daylength, was significantly enhanced in the absence of thyroid hormones. PMID- 3096518 TI - [Histamine-immunoreactive neurons in the hypothalamus of cats]. AB - The localization of histaminergic neurons in the cat brain was determined immunohistochemically with an antibody against histamine. We found that histamine immunoreactive neurons are observed exclusively in the posterior hypothalamus of colchicine treated cats. The larger group of neurons was found in the ventrolateral part of the posterior hypothalamus, including the tuberomammillary nucleus. Histamine-positive neurons were also observed in the supramammillary area and adjacent posterior hypothalamic area, as well as in the peri- and premammillary regions. In addition, numerous histamine immunoreactive fibers were detected, not only in the posterior hypothalamus, but also in other brain areas, such as the preoptic area of the anterior hypothalamus. PMID- 3096519 TI - [Risk of infection from enteral feeding]. PMID- 3096520 TI - [Sedation with flunitrazepam during spinal anesthesia]. AB - The clinical effects of flunitrazepam (FNZ) as IV sedative agent for spinal anaesthesia was studied. Of 112 elderly patients undergoing hip surgery, 40.2% have required a total dose of 26.6 +/- 2.3 mcg X kg-1. The repeat doses were 9.3 to 13.3 mcg X kg-1. A good state of sedation was obtained in 81% of patients, with a linear relationship between narcosis states and FNZ's doses. In 93% of cases, FNZ was provided peroperative amnesia without post-operative somnolence. No clinically adverse cardiovascular effects were encountered. There was a small, but statistically significant increase in arterial carbon dioxide tension. In summary, FNZ provided useful sedation. PMID- 3096521 TI - Current therapy of acute and chronic leukemia in adults. PMID- 3096522 TI - The evolving role of radiation therapy in the management of colorectal cancer. PMID- 3096523 TI - Chemotherapy for colorectal carcinoma. PMID- 3096524 TI - The ethical dilemma of phase I clinical trials. PMID- 3096525 TI - Malignant melanoma. PMID- 3096526 TI - Mohs technique. PMID- 3096527 TI - Resumption of hormonal therapy. PMID- 3096528 TI - Oncologic emergencies. PMID- 3096529 TI - [Methods of repairing nerve injuries of the arm in 115 cases]. PMID- 3096530 TI - [Thumb reconstruction using a forearm composite flap]. PMID- 3096531 TI - [A two-site ELISA using monoclonal antibodies in the diagnosis of early pregnancy]. PMID- 3096532 TI - [Epidemiologic analysis of abnormal hemoglobins in China]. PMID- 3096533 TI - [Raising the detection rate of lung cancer using bronchoscopy with hematoporphyrin aerosol inhalation]. PMID- 3096534 TI - [Nail-fold microcirculatory flow in liver cirrhosis: diabetes mellitus and systemic lupus erythematosus]. PMID- 3096535 TI - [Auditory dyslalia]. PMID- 3096537 TI - [Zinc protoporphyrin in the blood as a screening indicator of occupational hazards produced by lead]. PMID- 3096536 TI - [The sensitizing role of the gut-associated antigen of Schistosoma japonicum in granuloma formation around the ova]. PMID- 3096538 TI - [Replantation of severed fingers and restoration of digital function]. PMID- 3096539 TI - [Antenatal gene diagnosis of phenylketonuria]. PMID- 3096540 TI - [Some epidemiologic aspects of the aged in China]. PMID- 3096541 TI - Abstracts. XIX European Symposium on Calcified Tissues. June 15-19, 1986, Stockholm, Sweden. PMID- 3096542 TI - Single lever Humphrey A.D.E. low flow universal anaesthetic breathing system. Part I: Comparison with dual lever A.D.E., Magill and Bain systems in anaesthetized spontaneously breathing adults. AB - The single lever Humphrey A.D.E. anaesthetic system, in both coaxial and parallel (non-coaxial) forms, has recently been introduced. In principle the system offers efficient "universal" function by combining the advantages of Mapleson A, D and E systems. A within-patient comparison of its function in the Mapleson A mode (lever up) in spontaneously-breathing anaesthetized subjects was made to that of the original two lever A.D.E., the Magill (Mapleson A) and the Bain (Mapleson D) systems. The coaxial and parallel single lever A.D.E. systems functioned identically to each other and to the original two lever A.D.E. system, a mean fresh gas flow (FGF) of 51 ml X kg-1 X min-1 causing minimal rebreathing. Under identical conditions, the mean FGF required to just cause rebreathing increased to a mean of 71 ml X kg-1 X min-1 and 150 ml X kg-1 X min-1 with the Magill and the Bain systems respectively. With the single lever system, the switch to its Mapleson E mode for controlled ventilation involves the selection of the only alternative lever position (lever down) without further adjustment. The function and practical advantages in this E mode are presented in Part II. PMID- 3096543 TI - Single lever Humphrey A.D.E. lowflow universal anaesthetic breathing system. Part II: Comparison with Bain system in anaesthesized adults during controlled ventilation. AB - A clinical trial involving ten anaesthetized adult patients was conducted during controlled ventilation using the Humphrey A.D.E. system in the Mapleson "E" mode (lever down). With each patient acting as his or her own control, the parallel (non-coaxial) and coaxial versions of the single lever Humphrey A.D.E. system were compared, using capnography, to the Bain system (Mapleson D/E). All three systems behaved similarly with predictable patient normocarbia when a fresh gas flow of 70 ml X kg-1 X min-1 was used. The A.D.E. system has the added advantage that the switch from controlled to spontaneous ventilation (or vice versa) is achieved quickly and simply. Spontaneous, assisted or automatic controlled ventilation could be instituted at any time merely by the appropriate lever position. PMID- 3096544 TI - Treatment of porcine malignant hyperthermia: lactate gradient from muscle to blood. AB - Treatment of MH was studied in 21 pigs, using an isolated perfused caudal body preparation (L1 transection). Halothane one per cent triggered MH; data included oxygen consumption, blood/muscle lactate levels, plasma potassium, acid-base balance. Three treatment protocols had two phases each: A-1, discontinue halothane, inject dantrolene 7.5 mg X kg-1; A-2, inject HCO3- (113 +/- 6 mEq). B 1, Discontinue halothane, inject HCO3- (118 +/- 13 mEq); B-2, inject dantrolene 7.5 mg X kg-1; X C-1, Continue halothane, inject dantrolene 7.5 mg X kg-1; C-2, discontinue halothane, inject HCO3- (101 +/- 8 mEq). Dantrolene and HCO3- acted separately and differently: dantrolene reversed the hypermetabolism, both aerobic and anerobic, and HCO3- reversed the extracellular metabolic acidosis. Semitendinosus muscle biopsies demonstrated that both red and white muscle are involved in MH, that muscle lactate (to 35 mumol X g-1) consistently exceeded blood lactate (to 22 mumol X ml-1), and that blood lactate levels were slow to diminish following treatment. One could expect continued release of muscle lactate into blood, despite adequate therapy of MH; this might suggest a recurrence even when such is not the case. PMID- 3096545 TI - Reducing the costs of ICU admission in Canada without diagnosis-related or case mix groupings. AB - A prospective analysis of the cost of intensive care was carried out on 67 admissions to a multidisciplinary ICU. Admissions were grouped and investigated according to various criteria such as admitting diagnosis, admission status (elective vs emergency), severity of illness and outcome. Total ICU admission costs, total per diem ICU costs and per diem costs divided into fixed and variable cost items for the patient groups are reported. Lower total and per diem ICU charges were observed for elective surgical patients, patients with lower severity of illness as assessed by the Therapeutic Intervention Scoring system and survivors. Emergency admissions were more expensive than elective admissions when compared for total ICU admission costs. Length of stay was a significant factor in overall ICU costs. Within the variable cost items, the diagnostic laboratory was the single most costly item per day. As a result of this analysis, the authors propose several suggestions for reducing ICU costs independent of case-mix or diagnosis-related groupings of ICU patients. PMID- 3096546 TI - The influence of bile on the bioavailability of polynuclear aromatic hydrocarbons from the rat intestine. AB - The mechanisms governing absorption of polynuclear aromatic hydrocarbons (PAHs) are important since these carcinogenic compounds occur as solutes in dietary lipids. These highly lipophilic compounds are well absorbed in the intestine. Bile salt micellar solubilization probably facilitates their transport across the unstirred water layer to the enterocytes. To study the role of bile in the intestinal absorption of PAHs, conscious rats with bile duct and duodenal catheters were given isotopically labelled 2,6-dimethylnaphthalene (DMN), phenanthrene, anthracene, 7,12-dimethylbenzanthracene (DMBA), and benzo[alpha]pyrene (BP); the recovery of radioactivity in bile and urine was measured. The PAHs were given intraduodenally in corn oil with or without exogenous bile. Cumulative recovery of radiolabel in bile and urine over 24 h was used to assess the efficiency of absorption of the hydrocarbons with and without bile. The following values for absorption without bile (as percentage of absorption with bile) were obtained: DMN, 91.6%; phenanthrene, 96.7%; anthracene, 70.8%; DMBA, 43.4%; BP, 22.9%. The values for anthracene, DMBA, and BP were significantly less than 100% (P less than 0.05); the values for DMN and phenanthrene were not significantly different from 100%. The dependence of the tricyclic compound anthracene (a structural isomer of phenanthrene) on bile for its absorption correlates with its lower water solubility. These results are consistent with the concept that the unstirred water layer presents a significant barrier to the absorption of this group of compounds and that micellar solubilization facilitates the uptake process. PMID- 3096547 TI - Inhibition of release of a novel pituitary polypeptide, 7B2, follicle-stimulating hormone, and luteinizing hormone from rat anterior pituitary cells in vitro by human beta-inhibin. AB - We have recently purified a novel pituitary polypeptide designated 7B2. By raising polyclonal antibodies to a synthetic 7B2 fragment in rabbits, we have developed a sensitive and specific radioimmunoassay for this novel polypeptide, and it has been used for the study of the release of immunoreactive 7B2 from rat anterior pituitary cells in vitro. In addition, immunocytochemical study shows that 7B2 is present in the gonadotropin cells of rat anterior pituitary. The aim of the present studies is to investigate the effect of human beta-inhibin, testosterone, and combined testosterone plus human beta-inhibin on the induced release of immunoreactive 7B2, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in rat anterior pituitary cell culture in vitro. Our results show that both human beta-inhibin and testosterone effectively suppress the stimulatory effect of luteinizing hormone-releasing hormone (LHRH) on immunoreactive 7B2, FSH, and LH release. The present data indicate that the regulation of secretion of 7B2 and pituitary gonadotropins may be under a similar type of feedback mechanism. PMID- 3096548 TI - Cytotoxic factors toward neuroblastoma cells in trypomastigotes of Trypanosoma cruzi. AB - Homogenates of trypomastigotes of Trypanosoma cruzi (T.c) exhibited low-potency cytotoxic activity toward neuroblastoma cells. The cytotoxic activity was markedly decreased after preservation for 1 week, even at -20 degrees C. Trypsin and pronase E were shown to effectively enhance or restore the cytotoxic activity of T.c by producing some alteration in T.c, depending on concentrations of and treatment time with the enzymes. The cytotoxic factors were insoluble in saline and found in the chloroform extracts of a T.c homogenate. Analysis by thin-layer chromatography showed that the cytotoxic activity of T.c was found in the free fatty acids and lysophospholipids fractions. Of the free fatty acids present in T.c, eicosatetraenoic (20:4) and octadecadienoic (18:2) acids were the most cytotoxic. It was assumed that as much as 27.2% (w/w) of the total lipids of T.c consists of free fatty acids, and 1 mg of protein of the T.c homogenate contains 96 micrograms of free fatty acids. The abundant free fatty acids appear to account for the cytotoxic activity of the T.c homogenate, although they occurred in T.c under weakly active condition. PMID- 3096550 TI - Clinical experience with biliopancreatic bypass and gastrectomy or selective vagotomy for morbid obesity. AB - In 1980 Scopinaro described biliopancreatic bypass for the treatment of obesity. This procedure was aimed at selective malabsorption. The authors used Scopinaro's procedure in 33 patients, but in 17 they modified it by doing selective vagotomy with closure of the duodenum in continuity instead of a subtotal gastrectomy. Eighteen months after the operation, 88% of the patients had what the authors considered was a good to excellent result, that is a loss of more than 25% of the patient's initial weight. Morbidity of many kinds was encountered but most was self-limiting or easily corrected by medical means. From their experience the authors conclude that biliopancreatic bypass as a procedure for the treatment of morbid obesity should continue to be performed and evaluated. PMID- 3096549 TI - [Bacterial interference with skin colonization in germfree hairless mice]. AB - Bacterial colonization of the digestive tract and the skin was studied over a 3 week period in a group of 10 germfree HRS mice using Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa. Sequential utilization of two strains allowed us to carry out six assays and to show the presence of interference phenomena during colonization of the skin. When P. aeruginosa was given after challenge with S. aureus or S. epidermidis, it did not colonize the skin. If the first challenge was done with P. aeruginosa, this bacteria was eliminated within 10 days by S. aureus and S. epidermidis on the skin, but it succeeded in colonizing the digestive tract. When the first challenge was done with S. aureus, colonization of the skin and the digestive tract with S. epidermidis was prevented, whereas these two species were found in association when S. aureus was given in second place. None of the in vitro assays (mixed culture, bacteriocin production, adherence inhibition, antimicrobial activity) could explain the in vivo observations. PMID- 3096551 TI - Local hepatic tuberculosis, the cause of a painful hepatic mass: case report and review of the literature. AB - Local hepatic tuberculosis is an unusual form of extrapulmonary tuberculosis. The authors describe the case of a 39-year-old woman with this disease who posed diagnostic difficulties. She presented with abdominal pain, minimal constitutional symptoms, hepatomegaly and radiologic findings of a focal hepatic lesion. Laparotomy was required for diagnosis. A literature review revealed that most individuals with local hepatic tuberculosis have fever, night sweats and weight loss. Hepatomegaly is often the only abnormal physical sign. Minimally elevated serum bilirubin and alkaline phosphatase levels are common. Ultrasonography and computerized tomography will demonstrate a lobulated, hypoechoic liver mass. Definitive diagnosis requires demonstration of acid-fast bacilli in biopsy material obtained by percutaneous techniques or at laparotomy. Cultures of the diseased liver are usually negative. Antituberculous drug therapy appears to be the preferred method of treatment. PMID- 3096552 TI - Cyclical gonadotrophin and progesterone secretion in women with minimal endometriosis. AB - Concentrations of LH, FSH, oestradiol (E) and progesterone (P) were measured in serum of 12 women with minimal endometriosis and otherwise unexplained infertility. Values were compared with those on corresponding days relative to the pre-ovulatory LH peak (Day 0) in six fertile women. Three women exhibited cycle profiles of LH, FSH, E and P indistinguishable from those in the control group. In the remaining nine women cycle profiles for FSH and follicular phase profiles for LH were normal but eight exhibited a delay in P secretion and reduced total P output. LH concentrations were elevated during the early luteal phase in five subjects, two of whom had a second LH surge. These data suggest that luteal dysfunction and abnormal secretory patterns for LH may be contributory to infertility associated with endometriosis. PMID- 3096553 TI - The compromised host. Deficit-specific infection and the spectrum of prevention. PMID- 3096554 TI - Comparison of the effects of an ornithine decarboxylase inhibitor on the intestinal epithelium and on intestinal tumors. AB - Ornithine decarboxylase (ODC) catalyzes the rate-limiting step in the synthesis of polyamines, it has a short half-life, and its synthesis is under hormonal control. Recently, insight into the role of ODC and thus into the physiology of polyamines has been gained by the use of an inhibitor of ODC, difluoromethylornithine (DFMO). In the present report cell proliferation was measured by a stathmokinetic method in the crypt epithelium of the jejunum and colon of normal rats and in dimethylhydrazine-induced colonic tumors. Growth of human colon tumor xenografts in immunosuppressed mice and mouse colon tumor isografts was also assessed. Cell proliferation in primary colonic tumors was substantially suppressed by a single dose of DFMO at 100 mg/kg whereas the normal crypt epithelium of the small and large intestine required two doses at 400 mg/kg to produce a similar magnitude of inhibition of cell proliferation. DFMO was also found to suppress cell proliferation in, and the growth of, the transplantable colon cancers. Because of the apparent selectivity of the antimitotic activity of DFMO towards tumors, ODC inhibitors may prove to be useful anticancer drugs. PMID- 3096555 TI - Pharmacokinetics of intraventricular and intravenous N,N',N'' triethylenethiophosphoramide (thiotepa) in rhesus monkeys and humans. AB - The cerebrospinal fluid (CSF) and plasma pharmacokinetics of N,N',N" triethylenethiophosphoramide (thiotepa), an alkylating agent used for treatment of carcinomatous meningitis, were determined in rhesus monkeys in order to assess the relative advantage of intraventricular versus systemic administration of the drug. Following an i.v. thiotepa dose of 0.9 mg/kg (11 mg/sq m), peak plasma levels of parent drug reached approximately 1 microgram/ml. Thiotepa was rapidly equilibrated with lumbar and ventricular CSF. Systemic, lumbar, and ventricular exposure to the drug, measured as area under the curve (AUC), were similar in all cases. After a 1-mg intraventricular dose of thiotepa, peak ventricular levels were greater than 100 micrograms/ml. However, peak levels in the lumbar CSF at 1 h after intraventricular administration were less than 10 micrograms/ml. The AUC for ventricular CSF was nearly 100-fold greater for the intraventricular route than for the i.v. route; however, the AUC for lumbar CSF following intraventricular delivery was only 5% of the AUC for ventricular CSF. N,N',N'' Triethylenephosphoramide, an active metabolite of thiotepa observed in all fluids, appeared to have a much slower total body clearance than thiotepa. Comparison of the data obtained from monkey experiments with data from a patient with meningeal disease supports the use of the monkey as a model for intraventricular pharmacokinetics. The data presented indicate that there is no relative advantage to intraventricular administration of thiotepa at the doses currently used in clinical trials. PMID- 3096557 TI - Effect of inhibitors of ornithine decarboxylase on retrovirus induced transformation of murine erythroid precursors in vitro. AB - alpha-Difluoromethylornithine (DFMO) and methyl acetylene putrescine (MAP) are inhibitors of the rate limiting enzyme in polyamine synthesis, ornithine decarboxylase. We studied the effects of these compounds on the formation of retrovirus transformed erythroid colonies. DFMO was able to effectively reduce the number of transformed colonies at a concentration of 10(-3) M, whereas MAP achieved total inhibition at 10(-4) M. Putrescine, the product of ornithine decarboxylase, did not alter colony number by itself but it was able to overcome the inhibitory effects of both DFMO and MAP. Addition of DFMO at times after the initiation of culture decreased its effectiveness in reducing transformed colony numbers, while the converse was true for the erythroid stimulant, erythropoietin. We concluded from these data that DFMO and MAP probably diminished colony formation by inhibiting proliferation of the target cells for the retroviruses. PMID- 3096556 TI - Distinct functional domains on the recombinant human immune interferon molecule. AB - Two monoclonal antibodies directed against distinct epitopes of recombinant human immune interferon (rIFN-gamma) were used to investigate the relationship between the molecular organization of IFN-gamma and its various biological activities on cultured human melanoma cells. Both monoclonal antibodies inhibited the increase in the expression of cell surface human lymphocyte antigens Class I and II antigens and the antiproliferative and antiviral actions of rIFN-gamma. On the other hand neither monoclonal antibody affected the binding of rIFN-gamma to melanoma cells and its ability to reduce the expression of a high molecular weight-melanoma associated antigen. These data indicate that the functional domains of IFN-gamma responsible for antiviral activity, increased human lymphocyte antigen expression and antiproliferative effects on human melanoma cells may be distinct from that (those) involved in reduced expression of the high molecular weight-melanoma associated antigen and in IFN-gamma binding to cell receptors. PMID- 3096558 TI - Inhibition of dimethyl sulfoxide induced erythropoietic differentiation of murine erythroleukemia cells in culture. AB - The dimethyl sulfoxide induced erythropoietic differentiation of murine erythroleukemia cells, as determined by scoring benzidine positive cells, is inhibited by mitomycin C at concentrations that have no effect on cell proliferation. The inhibition occurs only when cells are treated with mitomycin C during induction and has a limit value of about 50%, independent of mitomycin C concentration. This limit value does not depend on cell heterogeneity since genetically homogeneous subclones, derived from DS19 clone, show levels of mitomycin C inhibition between 16 and 50%. Treatment with mitomycin C at different times after dimethyl sulfoxide addition shows that cell sensitivity to inhibition is not homogeneous during the induction period; it is maximal between 18 and 24 h from the start of induction and is observed with a concentration of mitomycin C as low as 25 fM. The inhibition of the benzidine positive phenotypic expression appears irreversible since this effect is observed on cells even several generations after those which were actually treated. PMID- 3096559 TI - Enhanced inhibition of colony formation of human renal cell carcinoma in soft agar by the combination of alpha-difluoromethylornithine and recombinant gamma interferon. AB - We studied the inhibitory activity of alpha-difluoromethylornithine (DFMO) and alpha-, recombinant beta-, and recombinant-gamma-interferons (alpha-, rec-beta-, and rec-gamma-IFNs) on in vitro growth of 3 established human urogenital tumors (KO-RCC-1 from renal cell carcinoma, Bewo from choriocarcinoma of the uterus, and HT-1197 from transitional cell carcinoma of the urinary bladder) and 16 primary renal cell carcinomas obtained by nephrectomy. Treatment with DFMO together with rec-IFN-gamma synergistically inhibited KO-RCC-1 cell growth in monolayer culture and in soft agar. The other two established cell lines were less susceptible to this treatment. Combination of DFMO and rec-IFN-gamma was more inhibitory than that of DFMO and either IFN-alpha or rec-IFN-beta. The polyamine content in KO RCC-1 cells was decreased to a greater extent by combined treatment with DFMO and rec-IFN-gamma than that in Bewo and HT-1197 cells. The effect of these agents in 11 of the 16 primary renal cell carcinomas, which could show clonal growth in double layer soft agar, was examined. More than 50% inhibition of colony growth was seen in only one case (9%) treated with 5 mM DFMO alone and in 2 cases (18%) treated with rec-IFN-gamma alone (1,000 units/ml) but in 10 of the 11 cases (91%) with the combined treatment. Our results indicate that combined treatment with DFMO and rec-IFN-gamma can be more effective than that with either agent individually in inhibiting cell growth of human renal cell carcinoma in vitro. PMID- 3096561 TI - In vitro sensitivity of normal and hereditary retinoblastoma fibroblasts to DNA damaging agents. AB - We investigated the ability of nine fibroblast cell strains from patients with the hereditary form of retinoblastoma (RB) to handle various types of DNA damaging agents and compared the results with those obtained in nine normal strains. Cell strains were exposed to gamma-radiation, which causes DNA scission; actinomycin D, a DNA-intercalating agent; and mitomycin C, a bifunctional alkylating agent leading to DNA-DNA cross-linking. Cell strains were studied for their ability to survive in a cytotoxicity assay. Nine normal strains exhibited a mean D0 (inverse of the slope of the straight line portion of the survival curve) of 134-178 cGy after radiation exposure, compared to a range of 119-186 cGy in the nine RB strains (P = 0.33). Similarly, exposure to actinomycin D led to D0 values of 0.024-0.069 microgram/ml in the nine normal strains and D0 values of 0.016-0.067 microgram/ml in the RB strains (P = 0.64). The nine RB strains did exhibit a small overall increase in sensitivity after exposure to mitomycin C, with D0 values ranging from 0.14-0.32 microgram/ml versus 0.19-0.66 microgram/ml in the nine normal strains (P = 0.002); however, when the two most resistant normal strains were excluded from analysis, results were similar. Three RB cell strains derived from individuals who had either developed second cancers or who had a family history of additional sarcomas consistently exhibited increases in sensitivity to all three DNA-damaging agents studied compared with other hereditary RB cell strains as well as normal strains. The results suggest that normal human fibroblast cell strains exhibit a wide response to DNA-damaging agents, especially chemical agents. Most hereditary RB strains exhibit sensitivity well within the normal range; however, strains from RB patients predisposed to second cancers exhibit increases in sensitivity to DNA-damaging agents. The heterogeneous ability to repair DNA damage may play a role in the development of second malignant neoplasms in hereditarily predisposed individuals. PMID- 3096560 TI - Comparison and characterization of growth inhibition in L1210 cells by alpha difluoromethylornithine, an inhibitor of ornithine decarboxylase, and N1,N8 bis(ethyl)spermidine, an apparent regulator of the enzyme. AB - The cellular effects of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and N1,N8-bis(ethyl)spermidine (BES), an apparent regulator of the enzyme were compared in cultured L1210 cells. Unlike DFMO, BES has no direct inhibitory effect on ODC activity. Rather the polyamine analogue is believed, from previous studies, to behave similarly to exogenous spermidine in its ability to suppress intracellular ODC activity but not in its ability to perform functions required for cell growth. The kinetics and extent of growth inhibition by 30 microM or 100 microM BES and 1 mM DFMO were nearly identical as were their effects on macromolecular precursor incorporation with leucine being the first and most significantly affected. By flow cytometry, neither BES nor DFMO induced obvious perturbations in the cell cycle. Both compounds effectively eliminated ODC activity in treated cells and depleted putrescine and spermidine pools with very similar kinetics of decline. These close similarities in drug effects between BES and DFMO, an established polyamine inhibitor, support previous indications that BES induces growth inhibition by depletion of cellular polyamines. BES differed distinctly from the ODC inhibitor by decreasing spermine pools, and by not increasing S-adenosyl-methionine decarboxylase activity, S adenosylmethionine pools, or stimulating cellular uptake of polyamines. The data suggest that enzyme regulation by polyamine analogues such as BES represents a viable alternative to enzyme inhibition as an antiproliferative strategy directed at polyamine biosynthesis. PMID- 3096562 TI - Enhancement by gamma-interferon of in vivo tumor radiolocalization by a monoclonal antibody against HLA-DR antigen. AB - Athymic nu/nu (nude) mice bearing s.c. human breast tumors were treated systemically with recombinant human gamma-interferon. These tumors were phenotypically negative for HLA-DR prior to therapy, but after 4 days of treatment, 80% of the cells expressed this antigen in vivo as assessed by immunoperoxidase (F. R. Balkwill et al., Eur. J. Cancer Clin. Oncol., in press, 1986). A radioiodine-labeled murine monoclonal antibody (TAL-1B5) against HLA-DR specifically localized to the tumors in recombinant human gamma-interferon treated but not in control mice. An isotype-identical murine monoclonal antibody that did not react with control or recombinant human gamma-interferon-treated tumors did not show any specific localization. These results demonstrate that specific localization to tumors of radio-labeled monoclonal antibodies to HLA-DR can be facilitated by systemic therapy with gamma-interferon. PMID- 3096563 TI - Ability of inhibitors of glycosylation and protein synthesis to sensitize cells to abrin, ricin, Shigella toxin, and Pseudomonas toxin. AB - A number of compounds that interfere with glycoprotein synthesis and transport have been tested for their ability to sensitize cells to cancerostatic protein toxins. Tunicamycin, swainsonine, cycloheximide, and puromycin sensitized Vero cells and HeLa cells to abrin and ricin, as we have found previously with monensin (K. Sandvig and S. Olsnes, J. Biol. Chem., 257: 7504-7513, 1982). Cycloheximide, but not swainsonine, sensitized Vero cells to Pseudomonas exotoxin A and Shigella toxin. The ability of ricin to intoxicate cells was much lower at 19 degrees C than at 37 degrees C and there was almost no sensitizing effect of cycloheximide and monensin at 19 degrees C. Studies by electron microscopy showed that ricin conjugated to horseradish peroxidase appeared in trans Golgi elements in Vero cells. Possibly, transport of ricin into the cytosol requires passage through the Golgi apparatus. The possibility that the sensitizing agents here described may be valuable in enhancing the action of immunotoxins is discussed. PMID- 3096565 TI - Mammalian G proteins: models for ras proteins in transmembrane signalling? AB - How do the p21v-ras proteins and their normal cellular counterparts regulate cell function? What is the molecular basis of action of these proteins? Biochemical, structural and functional similarities between the ras proteins and the vertebrate G proteins offer clues that may help to answer such questions. The G proteins couple a wide array of extracellular signals to regulation of a number of enzyme effectors, including adenylate cyclase, retinal cGMP phosphodiesterase and phospholipase-C. The RAS1 and RAS2 proteins of yeast regulate adenylate cyclase, whereas their close mammalian homologues, the p21ras proteins, do not. Both the ras and the G proteins are located at the cytoplasmic face of the plasma membrane and bind and hydrolyse GTP. Patchy amino acid sequence homologies between the two groups of proteins suggest a common evolutionary origin and common structural features, particularly in the GTP binding domain. In the GTP bound state both proteins are 'on' or activated, and each exhibits an intrinsic GTPase activity that turns off the active state. The analogies between the G and ras proteins suggest that the latter may also couple signal detector and enzymatic effector elements, and suggest strategies for identifying them. PMID- 3096564 TI - Correlations between immunological phenotype and karyotype in malignant lymphoma. AB - We have correlated immunological characteristics and karyotypic abnormalities from lymphomas in 118 patients. T-lymphomas differed significantly from B- and non-B-, non-T-lymphomas in having more normal metaphases, trisomy 19, and breaks at 1q21, 2q21, 3q27, 4q21, and 17q21 (P less than or equal to 0.03). Non-T lymphomas had breaks in 18q in one-half the cases, but only one of 11 T-lymphomas had such breaks (P = 0.02). Among B-lymphomas, specific chromosome abnormalities were associated with the type of immunoglobulin heavy but not light chain expressed. A break at 14q22 or q24 was associated with surface delta mu immunoglobulin (P = 0.02); trisomy 22 or a break in 22q and a break at 2q32 was associated with surface gamma-immunoglobulin (P less than 0.001); and trisomy 12 and a break at 2p13 was associated with cytoplasmic gamma-immunoglobulin (P less than 0.01). Among B-lymphomas, several cytogenetic abnormalities were associated (P less than or equal to 0.02) with expression of CD24 or CD9 surface antigens. Lack of CD24 was associated with breaks in 2p25, 5q, and 6q21; CD9 was associated with a break at 6q15. Associations with a specific immunological phenotype were not identified for cytogenetic abnormalities involving a band to which genes encoding immunoglobulin or the T-cell receptor have been localized. Breaks were common at 14q32, the genomic site of the immunoglobulin heavy chain loci, in B-, non-B-, non-T-, and T-lymphomas. In T-lymphomas this may be because this is the site of the AKT1 oncogene. Breaks were uncommonly found at the light chain loci or the genomic sites encoding the T-cell receptor. However, the recurring breakpoints associated with T-lymphomas were commonly found on chromosomes to which genes coding for various T-cell antigens have recently been provisionally assigned. PMID- 3096566 TI - The ras gene family. AB - Members of the ras multigene family have been found in virtually all eukaryotes, from yeast to mammals. ras is required for normal cell growth in the yeast Saccharomyces cerevisiae and in at least some mammalian cells. These genes induce tumorigenic transformation of established NIH 3T3 cells by increased expression of a normal ras gene, certain point mutations or amino acid deletion. In tumours, point mutation appears to be the most common mechanism of activation. The ras proteins are found at the plasma membrane, bind guanine nucleotides GDP and GTP and possess a GTPase activity. At least some ras proteins that have been activated by single amino acid substitutions possess a GTPase activity that is lower than that of the normal version. These results are consistent with the hypothesis that ras protein stimulates its putative target(s) when GTP is bound to it, as is true for the G regulatory proteins or elongation factor Tu. In Saccharomyces cerevisiae, ras has been shown to stimulate adenylate cyclase. However, there does not appear to be a direct interaction between ras and adenylate cyclase in mammalian cells. PMID- 3096567 TI - Synthesis of 1,4-dideoxy-1,4-imino-D-glucitol, a glucosidase inhibitor. AB - 1,2:5,6-Di-O-isopropylidene-D-glucitol was converted via its 1,4 dimethanesulfonate into the 1-azido-4-methanesulfonate which, after deprotection and treatment with barium hydroxide, afforded a 9:1 mixture of the corresponding 3,4- and 4,5-anhydro derivatives. Reduction of this mixture by transfer hydrogenation using ammonium formate in methanol and Pd/C as catalyst afforded 1,4-dideoxy-1,4-imino-D-glucitol (4), the structure of which was proved after acetylation by 1H-n.m.r. spectroscopy. Compound 4 is a potent alpha-D-glucosidase inhibitor (Ki 7 X 10(-4)M) and a less potent beta-D-glucosidase inhibitor (Ki 1.25 X 10(-4)M), and inhibits beta-D-galactosidase non-competitively. PMID- 3096568 TI - Actions of Aspergillus oryzae alpha-amylase, potato phosphorylase, and rabbit muscle phosphorylase a and b on phosphorylated (1----4)-alpha-D-glucan. AB - Aspergillus oryzae alpha-amylase [(1----4)-alpha-D-glucan glucanohydrolase, EC 3.2.1.1] produced O-(6-phosphoryl-alpha-D-glucopyranosyl)-(1----4)-O-alpha-D glucopyran osy l-(1----4)-D-glucopyranose (6(3)-phosphorylmaltotriose) and O alpha-D-glucopyranosyl-(1----4)-O-(3-phosphoryl-alpha-D-glucopyranosyl )- (1--- 4)-O-alpha-D-glucopyranosyl-(1----4)-D-glucopyranose (3(3) phosphorylmaltotetraose) from potato starch upon exhaustive hydrolysis. These products indicate that the enzyme hydrolyses the same linkages in the vicinity of the 6-phosphorylated residue as porcine-pancreatic alpha-amylase, but hydrolyses different linkages in the vicinity of the 3-phosphorylated residue when compared with B. subtilis and pancreatic alpha-amylases. Potato phosphorylase [(1----4) alpha-D-glucan:orthophosphate alpha-D-glucosyltransferase, EC 2.4.1.1] and rabbit muscle phosphorylase a and b were unable to by-pass the phosphorylated D-glucosyl residue of 6-phosphorylated (1----4)-alpha-D-glucan, leaving three D-glucosyl residues attached to the 6-phosphorylated residue on the non-reducing side. PMID- 3096569 TI - Potential for real-time processing of the continuously monitored electrocardiogram in the detection, quantitation, and intervention of silent myocardial ischemia. AB - Current technology for monitoring and analyzing the ST segment allows for accurate description of ST-segment deviation, which in most cases is a valid measure of myocardial ischemia. In this article, the authors describe a new method that utilizes microprocessor analysis of the electrocardiogram to detect ST-segment deviation in ambulatory subjects. This technique results in the ability to characterize the total ischemic burden over long periods of time and to intervene acutely in order to treat myocardial ischemia and possibly to prevent complications of coronary artery disease. PMID- 3096570 TI - Combined heart-lung transplantation for end-stage right ventricular failure. AB - Combined heart-lung transplantation is an effective means of treating end-stage right ventricular failure in selected patients. Perioperative mortality is less than 30 percent, and may be further reduced by more-rigorous patient selection. About one-third of the patients can be expected to have good and lasting results, with a return to a fully active and normal life. Life expectancy is not known inasmuch as the longest follow up so far is four-and-a-half years. There are, however, three areas of serious concern: (1) The risk of developing progressive airway damage (obliterative bronchiolitis and bronchiectasis) is high. It occurs in about one-half of the patients surviving surgery and may occur as late as two years after the operation. The pathogenesis of this process is not yet understood, but it may be reversible if detected very early and treated aggressively with corticosteroids; otherwise, it follows a course of steady deterioration. (2) Cyclosporine as a maintenance immunosuppressive drug leads to progressive and irreversible renal impairment. Alternative means of long-term immunosuppression will need to be developed in the future. (3) Graft intimal proliferation affecting both the coronary and the pulmonary vessels may eventually limit graft survival. PMID- 3096571 TI - The effects of pH and weak bases on the in vitro endocytosis of vitellogenin by oocytes of Drosophila melanogaster. AB - The endocytosis of labeled vitellogenin by the developing oocytes of Drosophila melanogaster is pH dependent and inhibited in the presence of primary amines as determined by culturing whole ovaries in vitro. When the pH of the culture medium is adjusted to 6.8 or above, the vitellogenic oocytes sequester labeled vitellogenin synthesized by the follicle cells. The endocytosis of vitellogenin is shown autoradiographically by the accumulation of labeled yolk spheres within the oocytes. When the pH of the medium is reduced to 6.6 or below, the oocytes fail to sequester labeled vitellogenin, as demonstrated by an increase in immunoprecipitable vitellogenin in the culture medium and a concomitant reduction in the number of labeled yolk spheres within the oocytes. Vitellogenin endocytosis is also impaired by the addition of the primary amines methylamine or chloroquine to the culture medium. Monensin, a carboxylic ionophore, is shown to inhibit completely the secretion of labeled vitellogenin from the follicle cells. PMID- 3096572 TI - Heterogeneity of the podocyte membrane in rat kidney as revealed by ethanol dehydration of unosmicated specimens. AB - The ultrastructure of the podocyte membrane was studied by means of transmission electron microscopy of unosmicated tissue samples after acetone or ethanol dehydration and subsequent embedding in a polyester resin. The podocyte membrane in glutaraldehyde (GA)-fixed, acetone-dehydrated samples consisted of a relatively thick, clear layer (about 6 nm) abutted by the dark staining cytoplasm and a dark surface layer. In GA-fixed, ethanol-dehydrated samples a striking intramembranous pattern was observed in the podocyte cell membrane. The luminal podocyte membrane was regularly perforated by gaps about 25 nm wide. In grazing sections these gaps appeared round and were separated by a honeycomb pattern of intact membrane. The abluminal membrane, in contrast, generally maintained its continuity. The clear layer of the podocyte membrane was thinner in ethanol dehydrated samples than in acetone-dehydrated ones. In tissue samples fixed with GA supplemented by ruthenium red, ethanol dehydration was not associated with cell-membrane perforations. Based on these observations as well as on biochemical data from the literature we suggest that in GA-fixed, unosmicated, acetone dehydrated samples the structural integrity of the podocyte membrane is well preserved, while ethanol dehydration extracts some specific material from regularly distributed domains in the podocyte cell membrane. PMID- 3096573 TI - Relationship between the organization of actin bundles and vinculin plaques. AB - The temporal pattern of the formation and dissolution of vinculin patches during experimental manipulation of the state of actin within the cell was studied. Cytochalasin D-induced retraction and disappearance of stress fibers is followed, with a brief delay, by the dissolution of vinculin-containing patches and the coordinated redistribution of both actin and vinculin into newly formed amorphous aggregates or foci. Recovery from cytochalasin treatment begins with a transformation of these foci into doughnut-shaped assemblies in which actin and vinculin are precisely co-localized. The emergence and growth of filament bundles is paralleled by the appearance of faint vinculin patches that gradually increase in size in parallel with the stress fibers. If stress fibers are stabilized by microinjected rhodamine-phalloidin against stimuli that normally induce a coordinated redistribution of actin and vinculin, also the vinculin patches persist. These observations indicate that treatments influencing the state of actin in the cell have corresponding effects on the stability of vinculin patches and suggest a strong interdependency of actin and vinculin organization. PMID- 3096574 TI - A model system for peptide hormone action in differentiation: interleukin 2 induces a B lymphoma to transcribe the J chain gene. AB - Physiological levels of a purified T cell hormone, interleukin 2 (IL-2), were found to stimulate a cloned murine B cell line (BCL1) to secrete pentamer IgM antibody. The peptide hormone acts at the cell surface via specific IL-2 receptors and induces changes in the 5' chromatin of the J chain gene that correlate with its transcription and with the production of the J chain protein required for pentamer IgM assembly. There was no effect of IL-2 on cell proliferation nor on mu heavy chain gene transcription. These results define a specific function for IL-2 in B cell differentiation. In addition, the IL-2/BCL1 system provides a model for examining the mechanism by which signals generated by hormone-receptor interaction are transmitted to the nucleus and regulate gene expression. PMID- 3096575 TI - N-myc amplification causes down-modulation of MHC class I antigen expression in neuroblastoma. AB - Amplification of the N-myc gene is correlated with increased metastatic ability of human neuroblastomas. We show here that overexpression of the N-myc gene in a rat neuroblastoma cell line following gene transfer causes down-modulation of class I histocompatibility antigen expression and increases in the in vivo growth rate and metastatic ability of these cells. N-myc-mediated down-modulation of MHC class I antigen expression could be reversed by treatment with interferon without affecting the steady state level of N-myc mRNA. No effect on MHC class I antigen expression was found when the N-myc gene was expressed in rat fibroblasts, indicating that some of the effects caused by N-myc gene amplification are cell type-specific. PMID- 3096576 TI - A stop transfer sequence recognizes receptors for nascent chain translocation across the endoplasmic reticulum membrane. AB - A stop transfer sequence derived from the extreme carboxyl terminus of membrane IgM heavy chain has been shown to confer predictable transmembrane orientation to secretory proteins by aborting translocation of subsequently synthesized protein domains. Here we demonstrate that, in certain peptide sequence contexts, the same stop transfer sequence is also capable of initiating domain translocation across the endoplasmic reticulum (ER) membrane. Translocation directed by a stop transfer sequence is similar to, but distinguishable from, the action of a conventional signal sequence. Translocation is dependent on participation of the ribosome and protein receptors both in the cytoplasm and in the ER membrane. Moreover, both amino- and carboxy-terminal flanking protein domains can be translocated. Unlike a signal sequence, the stop transfer sequence is not itself translocated across the membrane. These results have implications for the nature of signal sequences, stop transfer sequences, and their receptor interactions. PMID- 3096577 TI - Repression and turnover pattern fushi tarazu RNA in the early Drosophila embryo. AB - Embryonic expression of transcripts from the Drosophila gene fushi tarazu (ftz) progresses through a series of spatial patterns, culminating in a seven-banded pattern at the cellular blastoderm stage. We studied the generation of this pattern using inhibitors of RNA synthesis (alpha-amanitin) and protein synthesis (cycloheximide). Injections of alpha-amanitin revealed that ftz RNA turns over extremely rapidly in the embryo, and we think that this may be essential to effect rapid changes in ftz RNA patterns. Injections of cycloheximide added to the normal domains of ftz expression, creating novel expression patterns that were dependent on the time of injection. These novel patterns suggest that two superimposed systems of repression establish the normal, seven-banded pattern of ftz expression. One system sets up a banded pattern over the entire length of the embryo, and the other restricts actual expression to the middle portion of the embryo. PMID- 3096578 TI - Inducible binding of a factor to the c-fos enhancer. AB - We have identified a factor in nuclear extracts that binds to the c-fos enhancer. Treatment of A431 cells with epidermal growth factor results in a rapid increase in the level of transcription and a concomitant increase in binding of the factor to the enhancer. Surprisingly, as transcription decreases rapidly, the enhancer binding activity remains elevated. In addition, although HeLa cells exhibit no detectable transcription of the c-fos gene, they contain significant amounts of binding activity, comparable to those in induced A431 cells. These results suggest that regulation of c-fos transcription involves more than simply an increased level of a factor capable of binding the enhancer. Finally, transcription of c-fos in A431 cells is markedly induced by the tumor promoter TPA and the calcium ionophore A23187, yet neither induced an increased level of the enhancer-binding activity. These agents thus appear to activate c-fos transcription via a mechanism distinct from that used by epidermal growth factors. PMID- 3096579 TI - A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Kruppel, a Drosophila segmentation gene. AB - Kruppel (Kr), a segmentation gene of Drosophila, encodes a protein sharing structural features of the DNA-binding "finger motif" of TFIIIA, a Xenopus transcription factor. Low-stringency hybridization of the Kr finger coding sequence revealed multiple copies of homologous DNA sequences in the genomes of Drosophila and other eukaryotes. Molecular analysis of one Kr-homologous DNA clone identified a developmentally regulated gene. Its product, a finger protein, relates to Kr by the invariant positioning of crucial amino acid residues within the finger repeats and by a stretch of seven amino acids connecting the finger loops, the "H/C link." This H/C link is conserved in several nuclear and chromosome-associated proteins of Drosophila and other eukaryotic organisms including mammals. Our results demonstrate a new subfamily of evolutionarily conserved nuclear and possibly DNA-binding proteins that again relate to a Drosophila segmentation gene as in the case of the homeo domain. PMID- 3096580 TI - Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. AB - NF-kappa B is a nuclear protein, found only in cells that transcribe immunoglobulin light chain genes, that interacts with a defined site in the kappa immunoglobulin enhancer. This protein can be induced in pre-B cells by stimulation with bacterial lipopolysaccharide (LPS). The induction involves a posttranslational activation, and the combined action of LPS and cycloheximide causes a superinduction. An active phorbol ester also induces this factor, and with kinetics more rapid than those for LPS stimulation. Phorbol-ester-mediated induction of NF-kappa B was observed in a T cell line (Jurkat) and a nonlymphoid cell line (HeLa), and is therefore not restricted to B-lymphoid cells. We interpret these results to indicate that factors that control transcription of specific genes in specific cells may be activated by posttranslational modification of precursor factors present more widely. PMID- 3096581 TI - HLA antigens on human hemopoietic progenitors during embryonic-fetal life: expression and in vitro modulation. AB - We have analyzed the time course of the expression of HLA antigens on hemopoietic progenitors (BFU-E, CFU-E and CFU-GM) from human embryonic-fetal livers (FL). HLA ABC and Ia-like antigens are never detected on progenitor cells at 5-week post conception. Their expression initiates at 6-week and progressively increases thereafter, up to near-adult levels at 9-week. The time course of HLA antigen expression on erythroid precursors, derived from FL at corresponding gestational ages, parallels that observed on hemopoietic progenitors. Incubation of embryonic progenitors or precursors with medium conditioned by PHA-stimulated adult peripheral blood mononucleated cells induces a marked increase of the expression of both HLA-ABC and Ia-like antigens. Conversely, incubation with recombinant gamma-interferon causes a marked increase of HLA-ABC, but not Ia-like antigen expression, thus in contrast with results observed on adult monocytes. PMID- 3096582 TI - Antioxidants and blockers of arachidonate metabolism inhibit the mitogenic effects of TPA in hepatocytes: differences in the operative mechanisms according to the cell cycle setting. AB - A single exposure to a low concentration (10(-10) mol/l) of TPA doubled the size of the fraction of neonatal rat hepatocytes flowing into DNA synthesis within 24 hours in 4-day-old primary cultures kept in low-calcium (0.01 mmol/l) HiWoBa2000 synthetic medium, thereby evoking a phenotypically neoplastic feature in normal, i.e. non-initiated cells. Inhibition kinetics studies, in which several antioxidants and blockers of the arachidonate cascade were given, each by itself, simultaneously with or at various time intervals after TPA, showed that the early mitogenic effects of TPA, i.e. the commitment of GO hepatocytes to grow and the reactivation of hepatocytes poised at the G1/S boundary required oxygen radicals and all the main metabolites of arachidonate. Instead, the subsequent flow into S phase of TPA-committed hepatocytes was not controlled by oxygen radicals and prostaglandins but by retinoid-modulable activities and by products of the lipoxygenase and thromboxane synthase pathways of arachidonate metabolism. PMID- 3096583 TI - The physiology and pathophysiology of the factor VIII complex. AB - The factor VIII complex consists of two noncovalently linked proteins: von Willebrand factor (VWF) and factor VIII (FVIII). VWF plays an important role in primary hemostasis by mediating the adherence of blood platelets to the damaged vessel wall. A review of the literature on VWF is given with regard to its physicochemical properties and mode of action. FVIII acts as a cofactor in the factor Xa-generating enzyme complex of the intrinsic coagulation cascade. Starting with the recently published primary structure of FVIII, the literature is reviewed for structural information on FVIII. Also, an effort is made to characterize the interaction of FVIII with VWF and to discuss the possible physiological significance of FVIII-VWF complex formation. Interaction of FVIII with the clotting factors of the intrinsic pathway of coagulation is described in detail. Hemophilia and von Willebrand's disease (VWD) are both congenital bleeding disorders affecting a great many people. The different variants of these diseases are described with some reference to therapy and detection. PMID- 3096585 TI - Fatty acid composition of phospholipids and neutral lipids and lipid peroxidation in human breast cancer and lipoma tissue. AB - Since unsaturated fatty acids have been shown to control cell division experimentally the fatty acid composition in human mammary cancers as compared with the healthy surrounding tissue was studied. Both phospholipid and neutral lipid fractions were extracted for study and further lipid peroxidation expressed as thiobarbituric acid reactive substances was measured. For a comparison a benign adipose tissue tumor, lipoma, was studied. There was a 3.6-fold increase in phospholipid contents of cancer as compared with a reference tissue. No such differences were observed between lipoma and surrounding adipose tissue. In the phospholipid fatty acids of mammary cancers there was a marked increase in the relative amounts of unsaturated fatty acids, especially arachidonic acid, while saturated fatty acids were decreased, as compared with a healthy reference breast tissue or lipomas. The data suggest that the fatty acids might have a role in the development of breast cancer, possibly related to the formation of reactive metabolites of unsaturated fatty acids in the initiation of cancer or to their promotional effects. PMID- 3096584 TI - Possible involvement of a lanthanide-sensitive protein kinase C substrate in lanthanide promotion of neoplastic transformation. AB - The rare earth elements lanthanum and terbium (0.1-1.0 mM), pharmacological analogs of calcium, induced neoplastic transformation of 12-O tetradecanoylphorbol-13-acetate (TPA)-sensitive (P+) and to a lesser extent TPA resistant (P-) preneoplastic mouse JB6 epidermal cells. A maximum of 2500 anchorage-independent colonies per 10(4) cells were induced in P+ lines, a response comparable to that induced by phorbol esters (1.6-16 nM). The maximum lanthanide-induced colony yield in P- lines was 20% of that in P+ lines (approximately 550 colonies), and was observed under conditions where TPA induced less than 30 colonies per 10(4) cells. Lanthanides and TPA produced a synergistic effect on colony size in P+ cells. Lanthanides are not promoting transformation merely by mimicking high calcium: adding exogenous extracellular calcium (up to 50.0 mM) or using calcium ionophore (up to toxic concentrations) to increase intracellular calcium does not promote transformation. Lanthanum will substitute for calcium in activating partially purified protein kinase C (PKC), the calcium dependent phorbol ester receptor. However, lanthanides must be promoting transformation by a mechanism other than PKC activation because lanthanides failed to activate PKC in intact JB6 cells. Three independent experiments showed a lack of lanthanum effect on PKC-dependent events in intact cells. First, in contrast to TPA, lanthanum pretreatment of JB6 cells did not produce elevated phosphorylation of an 80-kd substrate. Second lanthanum pretreatment did not cause decreased PKC activity after prolonged exposure. Third, lanthanum and TPA affected epidermal growth factor binding with a different magnitude, time course and calcium dependency. We found, however, a PKC substrate in P+, P- and tumorigenic cell lines that is sensitive to lanthanum and increases its migration in sodium dodecylsulfate-polyacrylamide gels from 23 to 21 kd. The above data suggest that: (i) alterations in cation binding may be sufficient for inducing the transformed phenotype; and (ii) lanthanide promotion of neoplastic transformation may be linked to a lanthanide-sensitive PKC substrate, but is not due to a direct PKC activation. PMID- 3096586 TI - Quantitation of nuclear aberrations as a screen for agents damaging to mammary epithelium. AB - The early nuclear damage caused by two known breast carcinogens, radiation and 7,12-dimethylbenzanthracene (DMBA), was quantitated by scoring for nuclear aberrations in mammary epithelium. Seven-week-old C57BL/6J female mice were irradiated with whole body gamma radiation or were given various doses of DMBA. The terminal end buds and ducts were separated and processed for histological preparation. The number of nuclear aberrations per 1000 cells was scored from coded slides. Animals receiving no treatment had a low level of these figures in their terminal end buds (34 +/- 7/1000 cells) but the number increased in a dose related manner to a maximum of 161 +/- 20/1000 cells when they were treated with 8 Gy. Apoptosis in the ductal epithelium was much less frequent than in the terminal buds and the quantitation of nuclear aberrations from these structures was a less sensitive and reliable indicator of damage. DMBA and N-nitroso-N methylurea are breast carcinogens from the polycyclic aromatic hydrocarbon and nitroso classes respectively. These chemicals cause increases in the nuclear aberration incidence in the terminal end buds but related carcinogens with different target specificities and noncarcinogens do not appear to produce such elevations. These results suggest that the quantitation of nuclear aberrations in breast epithelium might be used as a short-term, tissue-specific screen for breast carcinogens. PMID- 3096587 TI - Effect of D,L-2-difluoromethylornithine and endocrine manipulation on the induction of mammary carcinogenesis by 1-methyl-1-nitrosourea. AB - The purpose of this investigation was to establish an efficient route and dose regime for the long-term administration of tamoxifen in the study of mammary tumorigenesis in the rat. The second objective of this work was to determine whether treatment with D,L-2-difluoromethylornithine (DFMO), a synthetic inhibitor of the enzyme ornithine decarboxylase, would reduce the occurrence of mammary cancers in tamoxifen-treated or ovariectomized rats. A total of 265 female Sprague-Dawley rats were assigned to one of two experimental protocols. All animals were injected with 50 mg 1-methyl-1-nitrosourea (MNU) per kg body wt at 50 days of age. In experiment 1, beginning 7 days after the injection of the carcinogen, animals were assigned to one of six groups which received either 0, 1 or 5 mg tamoxifen citrate per kg AIN-76A purified diet in addition to either no DFMO or a 0.125% w/v solution of DFMO as the drinking water. The experiment was terminated 180 days following carcinogen treatment. Treatment with tamoxifen resulted in a dose-dependent reduction in cancer incidence, and the number of cancers induced and significantly prolonged the median cancer-free time. This effect was also accompanied by a decrease in the rate of body weight gain. Treatment with DFMO delayed latency and reduced tumor number. DFMO in addition to tamoxifen (1 mg/kg diet) further prolonged latency. In experiment 2 each animal was assigned to one or four treatment groups when its first palpable mammary tumor was detected. At that time each was either ovariectomized or sham-operated. In addition, the rats were either provided no DFMO or a 0.5% w/v solution of DFMO as the drinking water. The study was terminated 35 weeks following carcinogen injection. Ovariectomy significantly inhibited the occurrence of additional mammary tumors. Ovariectomy plus DFMO was more effective than ovariectomy alone in reducing tumor number. Collectively, these observations indicate that suppression of polyamine biosynthesis via the systemic administration of DFMO inhibits the development of ovarian hormone insensitive mammary tumors. PMID- 3096588 TI - Mechanisms of anti-carcinogenesis by indole-3-carbinol: effect on the distribution and metabolism of aflatoxin B1 in rainbow trout. AB - Indole-3-carbinol (I3C), a component of cruciferous vegetables, was previously shown to inhibit aflatoxin B1 (AFB1) carcinogenesis in trout. The purpose of this study was to examine the effect of I3C on AFB1 metabolism and hepatic DNA adduct formation in vivo and in vitro. When fed at 0.2%, I3C produced a 70% reduction in average in vivo hepatic DNA binding of injected AFB1 over a 21-day period when compared to controls. A 24-h distribution study of injected tritiated AFB1 in I3C fish showed less total radioactivity in the blood and liver at all times examined, compared to controls. These reductions were due primarily to reduced levels of AFB1 bound to red blood cell DNA, reduced plasma levels of the primary metabolite aflatoxicol (AFL), and decreased levels of AFB1 and polar metabolites present in the liver of I3C fish. In contrast to blood, total radioactivity was significantly elevated in the bile of I3C fish resulting from a 7-fold increase in aflatoxicol-M1 glucuronide levels over controls. No difference was observed in concentration of AFL glucuronide, the primary conjugate present in control fish. There was no difference in total radioactivity remaining in the carcass of I3C or control fish. AFB1 metabolism in freshly isolated hepatocytes from I3C fish showed 20% less DNA binding in a 1-h assay, with a 2-fold increase in aflatoxin M1 production. Addition of I3C to control hepatocytes at levels of 1, 10 or 100 microM had no effect on AFB1 DNA binding. These findings indicate that I3C inhibition of AFB1 hepatocarcinogenesis in trout involves substantial changes in the pharmacokinetics of carcinogen distribution, metabolism and elimination, leading to significantly reduced initial hepatic-nuclear DNA damage in vivo. PMID- 3096589 TI - Mouse skin tumor promoting activity of orange peel oil and d-limonene: a re evaluation. AB - Orange peel oil has previously been shown to be a promoter of mouse skin tumors. It has been assumed that this activity is due to its major (95%) constituent, d limonene. We have tested both orange peel oil and purified d-limonene as skin tumor promoters in a two-stage skin carcinogenesis model in which tumors were initiated with 7,12-dimethylbenz[a]-anthracene. We confirmed that topically applied orange peel oil is a very weak promoter of both skin papillomas and carcinomas. However, this promotional activity could not be accounted for by topically applied d-limonene. We thus feel that one or more minor components of orange peel oil has promotional activity. Neither orange peel oil nor d-limonene had promotional activity when given via the diet. PMID- 3096590 TI - The cerebral circulatory response during canine anaphylactic shock. AB - Radiolabeled microspheres were employed to measure the cerebrovascular response to severe anaphylactic-induced hypotension in pentobarbital-anesthetized dogs. A rapid drop in mean arterial pressure (MAP, 140 to below 50 mm Hg) coincided with total and regional cerebral blood flows (CBF) that were not significantly different from prechallenge values. While blood flow to the occipital region (highest measured region of the brain) was significantly greater than that of brainstem regions prior to and during the shock regimen, no major redistributional phenomena occurred to any cerebral region. These findings were in contrast with other reports that demonstrated a loss in CBF and a redistribution of regional CBF as perfusion pressures declined below 55 to 60 mm Hg. To investigate whether the maintenance of CBF during severe anaphylactic hypotension was associated with cerebral hypoxia or hypercapnia, we employed in a second group of dogs the technique of venous drainage from the confluens sinus, so that the cerebral arterial-venous difference for blood gases and other blood components could be determined. Similar to our previous findings, CBF was maintained to perfusion pressures of 39 +/- 4 mm Hg. The drop in cerebral vascular resistance during the severe hypotensive period was not associated with a significant decline in arterial PO2, or a significant increase in arterial PCO2, A-V PO2, or V-A PCO2. Our results suggest that the fall in cerebral vascular resistance during anaphylactic-induced hypotension would not be associated with a severely altered cerebral metabolism. PMID- 3096591 TI - The effects of alpha adrenergic blockade on arachidonic acid metabolism and shock sequelae in endotoxemia. AB - Previous studies have suggested that increased alpha adrenergic activity stimulated prostaglandin synthesis and may be involved in the modulation of eicosanoid metabolism. These observations prompted investigation of the effect of the alpha adrenergic receptor antagonist phenoxybenzamine and the cyclo-oxygenase inhibitor indomethacin on endotoxin-induced shock severity, and on plasma immunoreactive iTxB2 and i6-keto-PGF1 alpha, the stable metabolites of TxA2 and PGI2, respectively. Pretreatment with indomethacin alone blunted the endotoxin- (8 mg/kg) induced hypoglycemia. Phenoxybenzamine pretreatment also blunted endotoxin-induced mortality (LD80), hypoglycemia, hemoconcentration, and decreased plasma beta-glucuronidase (BG). The combination of phenoxybenzamine and indomethacin resulted in the improvement of all indices of shock severity. Rats pretreated with phenoxybenzamine and indomethacin alone or conjointly also exhibited significantly (P less than 0.05) enhanced survival compared to that of shocked control rats. Percent survival at 48 hr was 24, 64, 80, and 92 in untreated, indomethacin, phenoxybenzamine, and indomethacin + phenoxybenzamine treated, respectively. Mean plasma iTxB2 values at 30 min postendotoxin (15 mg/kg i.v.) were 1,532 +/- 319 pg/ml (N = 10). Phenoxybenzamine pretreatment decreased iTxB2 to 719 +/- 114 pg/ml (N = 10). Phenoxybenzamine pretreatment decreased iTxB2 to 719 +/- 114 pg/ml (N = 10) (P less than 0.05). Plasma i6-keto-PGF1 alpha was increased 4 hr after endotoxin in shocked controls to 4,161 +/- 885 pg/ml (N = 5) and attenuated by phenoxybenzamine to a value of 1,184 +/- 363 pg/ml (N = 4) (P less than 0.05). The results suggest that increased alpha adrenergic activity may be an important stimulus for arachidonic acid metabolism during endotoxemia. PMID- 3096592 TI - Terfenadine reduces skin and conjunctival reactivity in grass pollen allergic children. AB - Terfenadine suspension, 30 mg b.i.d., was compared with placebo in a randomized, double-blind cross-over study in twenty-five children, 6-12 years of age, with grass pollen induced allergic rhinoconjunctivitis. The patients were treated during two 7-day periods separated by a 4-day wash-out period. Efficacy was assessed during a period without provoking pollen in the air. At the end of each treatment period, skin-prick tests were carried out in quadruplicate with three concentrations of grass pollen extracts (identical batches of Pharmalgen) and histamine HCl, 1 and 10 mg/ml, as were conjunctival provocations with the same grass pollen. The mean size of weals caused by allergen and histamine was significantly smaller after terfenadine than after placebo; in fact, terfenadine increased the tolerance to the allergen by a factor of ten. Similarly, the tolerance to conjunctival provocation was significantly increased during terfenadine treatment as compared with placebo. There was no significant difference between the treatments in scores for alertness and salivation. Seasonal symptoms were mild when the children were allowed to use terfenadine in an open follow-up study. Thus, terfenadine reduced specific as well as non specific reactivity in grass pollen allergic children and caused few side effects. PMID- 3096594 TI - A simple radial immunodiffusion method for assay of beta 2-microglobulin in serum. AB - In this method for clinical measurement of beta 2-microglobulin, a 10 g/L agarose gel containing anti-beta 2-microglobulin is used, with subsequent staining with Coomassie Blue. Although the method is slow (requiring 30 h), it is inexpensive, reliable, and accurate over the range of 1 to 10 mg/L, and is useful in the determination of beta 2-microglobulin in serum and cerebrospinal fluid. A modified procedure in which staining with silver is used may be sufficiently sensitive for the clinical assay of urine. PMID- 3096593 TI - Simultaneous liquid-chromatographic determination of 3,4-dihydroxyphenylglycol, catecholamines, and 3,4-dihydroxyphenylalanine in plasma, and their responses to inhibition of monoamine oxidase. AB - This is a reversed-phase liquid-chromatographic method, with electrochemical detection, for simultaneously measuring, in plasma, the concentrations of the catecholamine precursor dihydroxyphenylalanine (DOPA); the endogenous catecholamines norepinephrine, epinephrine, and dopamine; and the deaminated catecholamine metabolites dihydroxyphenylacetic acid (DOPAC) and dihydroxyphenylglycol (DHPG). We used this method to assess effects of monoamine oxidase (EC 1.4.3.4) inhibition in humans. Plasma DHPG concentrations as determined by the present method (mean 826, SEM 61 ng/L) were similar to those found by other methods. Inhibition of monoamine oxidase (by administering deprenyl or tranylcypromine) decreased plasma DHPG by greater than 65%, plasma DOPAC by greater than 50%, and plasma DOPA by about 20%, without consistently affecting norepinephrine or epinephrine. Simultaneous measurement of DOPA, catecholamines, and DHPG may be useful for examining the synthesis, release, and intraneuronal metabolism of norepinephrine. The assay method is rapid, reliable, and simple, and it provides a more comprehensive assessment of noradrenergic nervous function than does measurement only of catecholamines. PMID- 3096595 TI - Simple spectrophotometric quantification of urinary excretion of glycosaminoglycan sulfates. AB - We describe a simple, rapid, precise, and sensitive spectrophotometric method for measuring urinary glycosaminoglycan (GAG) sulfate excretion. The GAG sulfates are precipitated with cetylpyridinium chloride, resuspended in water, and mixed with the basic dye 1,9-dimethylmethylene blue to produce a complex with the polyanionic molecule of sulfated GAGs. Absorbance is read at 535 nm. The standard curve for reaction was linear up to 12 micrograms of the different GAGs: dermatan sulfate, heparan sulfate, keratan sulfate, chondroitin 4-sulfate, and chondroitin 6-sulfate. Within- and between-run precision (CV), measured at three different GAG concentrations (normal and pathological), varied from 1.6% to 2.5% and from 1.8% to 4.5%, respectively. Analytical recovery ranged from 71% to 107%. Urinary GAG excretion, measured by this procedure, correlates (r = 0.837; p less than 0.001) with the values obtained with the borate-carbazole reaction (Anal Biochem 1962;4:330-4). PMID- 3096596 TI - Can nutritional criteria help predict outcome in hospitalized patients? AB - The following nutritional criteria were evaluated for their usefulness in predicting outcome in a prospective study of 66 randomly selected hospitalized patients with a variety of diagnoses: total protein, albumin, and transferrin concentrations in serum, creatinine height index, weight height index, phenylalanine/tyrosine ratio (Phe/Tyr), concentration of branched-chain amino acids in serum, and ratio of essential to nonessential amino acids in serum. The cases were followed from admission to discharge, and were classified into the following three groups: 43 "well"; 14 with "complications" but recovered; and nine "dead". Statistical analysis (Scheffe's s-test) demonstrated the means of "well" and "dead" groups to be different for total protein, albumin, transferrin, and Phe/Tyr. In individual patients the nutritional criteria, even for those with fatal outcome, were poor indicators of outcome. These nutritional criteria are useful in identifying hospitalized groups that are at maximum risk (i.e., death), but are much less useful for individual patients. PMID- 3096597 TI - Analytical evaluation of four sensitive assays of thyrotropin, including effects of variations in patient sampling. AB - Four immunometric kits for thyrotropin with detection limits below 0.1 milli-int. unit/L were evaluated with respect to accuracy, precision, specificity, matrix effects, and high-dose "hook" effect. We also studied variations of values related to the patients' sex and age and time of the day and season when samples were collected. Correlation among the four methods was excellent, except for a few samples, and the interference in these samples could be abolished by adding mouse serum or "suppression medium." These phenomena can also be expected to occur in other immunometric assays involving monoclonal antibodies. With some modifications all tests are suitable for a clinical study of the usefulness of the thyrotropin assay as a primary test for thyroid function. PMID- 3096598 TI - Nephelometric assay of apolipoprotein A-I with a centrifugal analyzer. AB - We developed an automated immunonephelometric assay for quantification of human apolipoprotein A-I (apo A-I) with a fluorescence light-scattering microcentrifugal analyzer. The presence of polyethylene glycol and Tween 20 in the reaction mixture ensures maximum exposure of the antigenic sites of the apoprotein so that immune complex formation occurs more rapidly (reaction is complete within 2 min) and to a greater extent. Lipemia and hemolysis do not interfere with the measurement of apo A-I. The method requires only 10 microL of specimen and is fast and easy to perform. Results vary linearly with apo A-I concentrations to 2.5 g/L. Assay precision (CV) was 3.1% for a specimen with an apo A-I concentration of 1.45 g/L, and the lower limit of detection was 0.15 g/L. Values for a candidate Reference Material agree well with those reported in an international survey (Clin Chem 1985;30:223-8). PMID- 3096599 TI - Falsely high results for triglycerides in patients receiving intravenous nitroglycerin. PMID- 3096600 TI - Immunonephelometric measurement of urinary albumin by a Cobas Bio centrifugal analyzer with fluorescence attachment. PMID- 3096601 TI - Transthyretin as measured in capillary and venous plasma. PMID- 3096602 TI - Discrepant serum FT4 values--a TBG dependency? PMID- 3096603 TI - An immunofluorometric assay for C-reactive protein with labeled IgG fraction. PMID- 3096604 TI - Cobaltic-EDTA as a marker for estimating trapped plasma. PMID- 3096605 TI - Inaccurate measurement of a polymeric IgA myeloma protein by nephelometric and fluorometric instrumentation. AB - The concentration of IgA in a serum was 5.99 g/L as assayed nephelometrically with reagent from one company, but varied between 5 and 3 g/L (for sixfold and 36 fold dilutions, respectively) without giving a definitive answer when assayed with reagent from another source. Immunofixation electrophoresis indicated an IgA lambda monoclonal protein of 45 g/L. Radial immunodiffusion showed two components, having a total concentration of 41 g/L. By fluorometry the IgA was 3.1 g/L. Increasing the dilution caused the (dilution-corrected) lower values to increase. Although the most frequent cause of such discrepant findings is an IgA2 myeloma, which occurs in about one of every 100 myeloma cases, Ouchterlony double diffusion indicated the major component to be IgA1. A polymer, Mr 670,000, was identified by column chromatography. Contrary to the usual behavior of polymers assayed with radial immunodiffusion, which underestimates their concentration, this polymer reached equivalency in agreement with its true concentration as assayed by the Mancini-Heremans technique. PMID- 3096606 TI - Measurements of total carbon dioxide made at low range with an ion-selective electrode (RA-1000) PMID- 3096607 TI - Diagnostic performance of two new analog assays for free thyroxin. PMID- 3096608 TI - Nephelometry of the kappa/lambda light-chain ratio in serum of normal and diseased children. AB - We determined, immunonephelometrically, the ratio between the two types of light chains of immunoglobulins, kappa and lambda, in serum of 94 children, ages 0.4 to 14 years, with no manifest immunological disorders. Children with an abnormal protein pattern by immunoelectrophoresis show other values for this ratio than do children in this reference group. We also determined the ratios for children with IgA deficiency (I), juvenile rheumatic arthritis (II), and acute lymphoblastic leukemia (III). Children with I show the same kappa/lambda ratios as for the children in the reference group. Children with II also show the same mean kappa/lambda ratios, but a significantly wider range of ratios. In children with III, the ratio during chemotherapy is slightly depressed, significantly lower than after cessation of therapy. All groups--healthy children and patients--show an increase in kappa-chain-bearing immunoglobulins with age, but the concentration of lambda-chain-bearing immunoglobulins remains relatively constant. PMID- 3096609 TI - Pregnancy-specific beta 1-glycoprotein in serum in monoclonal gammopathies: relationship with serum beta 2-microglobulin, and cellular origin. AB - Pregnancy-specific beta 1-glycoprotein (SP1) was assayed by particle-counting immunoassay in serum from 86 healthy blood donors and 236 patients with various types of gammopathy. A concentration of 1 microgram/L was taken as the upper normal limit. Abnormally high values were found in one of 10 patients with monoclonal gammopathy of undetermined significance, in 65% of 152 patients with multiple myeloma, in 84% of 64 patients with Waldenstrom's macroglobulinemia, and in seven of 10 patients with monoclonal gammopathies associated with other myeloproliferative disorders. In a study of 90 myeloma patients, the SP1 value correlated (p less than 0.001) with the concentration of beta 2-microglobulin in serum, a value which had been corrected for possible renal dysfunction, but not with the concentration of the monoclonal component. SP1 was detected by direct immunofluorescence in myeloma cells of bone-marrow smears from six of 10 patients with myelomatosis. These six patients had serum SP1 values greater than 1 microgram/L, whereas the four patients with fluorescence-negative myeloma cells had SP1 values less than 1 microgram/L. PMID- 3096610 TI - Radial-immunodiffusion assay of human apolipoprotein A-I with use of two monoclonal antibodies combined. AB - We produced and characterized several monoclonal antibodies directed toward human plasma apolipoprotein A-I. Two of them, A-I-12 and A-I-57, individually precipitated purified or native high-density lipoprotein in agarose gel by double immunodiffusion. Because radial immunodiffusion performed with a single monoclonal antibody gave faint and diffuse rings of precipitation, we developed and optimized working conditions for using these two monoclonal antibodies combined to determine apolipoprotein A-I in human plasma. This combination gave easy-to-measure, clear, sharp rings, and linear and parallel standard curves for HDL3 (the primary standard) and a reference serum (the secondary standard). Moreover, no pretreatment of samples with dissociating agents or detergents is necessary. The assay was complete after overnight incubation, as compared with two to three days when polyclonal antisera were used. Apolipoprotein A-I concentrations as measured in 128 normolipidemic subjects and in 72 patients with various lipid disorders by the radial immunodiffusion technique with monoclonal antibodies (x) compared well (r = 0.882; y = 1.029x-0.036) with those measured by radial immunodiffusion with polyclonal antisera (y). PMID- 3096611 TI - Age dependence of tissue plasminogen activator concentrations in plasma, as studied by an improved enzyme-linked immunosorbent assay. AB - A procedure for improving the specificity of enzyme-linked immunosorbent assays (ELISA) was devised, based on addition of antigen-specific or non-immune immunoglobulins to the citrated plasma sample and defining the difference in assay response between these two mixtures as the antigen-specific part of the response. When applied to measurement of tissue plasminogen activator (t-PA; EC 3.4.21.31) antigen in plasma, this procedure resulted in elimination of the overestimates obtained in a large proportion (10-20%) of patients' samples when assayed according to the conventional ELISA technique. Basal t-PA concentrations in plasma were found to be highly age-dependent, normal values being about 3 micrograms/L for adults near 30 years of age and about 10 micrograms/L for those over 60. Patients with gallbladder stone disease had increased mass concentrations of t-PA in plasma, even when corrected for the age effect; patients with multi-infarct dementia did not. PMID- 3096612 TI - Enhanced luminescence immunoassay: evaluation of a new, more sensitive thyrotropin assay. AB - We measured thyrotropin (TSH) with an enhanced luminometric assay ("Amerlite"; Amersham International). The detection limit of the assay is 0.02 milli-int. unit/L. Within-assay precision was 6.7 and 7.8% at 3.77 and 12.1 milli-int units/L, respectively, and between-assay precision was almost identical, whether singleton or duplicate samples were assayed. TSH measured in 132 euthyroid subjects ranged from 0.06 to 4.13 milli-int. units/L (mean 1.52, SD 0.86). Similar concentrations were found in 20 healthy pregnant women and 19 of 20 healthy post-menopausal women (one of whom had undetectable TSH). In 17 patients with primary hypothyroidism, TSH concentrations ranged from 9.34 to greater than 200 milli-int. units/L; and in 53 of 59 patients with hyperthyroidism, TSH concentrations were undetectable, ranging in the remaining six from 0.03 to 0.06 milli-int. unit/L. Results for TSH in 28 patients stimulated with thyroliberin were consonant with the results of the thyroliberin test in 25 cases. Thus, for most patients, measurement of a basal TSH concentration evidently will predict their thyroidal status and also the response to thyroliberin, but a few will require additional tests of thyroid function. PMID- 3096613 TI - Discrepancy between uptake of serum triiodothyronine as measured by albumin and charcoal methods in nonthyroidal illnesses. AB - Triiodothyronine (T3) uptake as determined with albumin (AT3U) and with charcoal (CT3U) as binders were compared for patients with low-T3 syndrome. Both T3U values were identical in normal subjects and in patients with thyroidal disorders, pregnancy, low thyroxin-binding globulin (TBG), or acute hepatitis with high concentration of TBG. In the low-T3 syndrome, AT3U was significantly higher than CT3U (38.5 +/- 7.2% vs 29.4 +/- 4.9%, mean +/- SD, n = 37, p less than 0.001), and this difference increased as TBG and albumin concentrations decreased. Decreasing the concentration of TBG and albumin in serum by dilution increased the AT3U more than the CT3U value. Adding albumin to serum decreased AT3U, but not CT3U, when serum TBG and albumin concentrations were low. The free thyroxin (T4) index as calculated by the AT3U ratio and T4 more accurately reflects the concentration of free T4 in low-T3 syndrome than does the index calculated from the CT3U ratio and T4. Thus AT3U is determined primarily by changes in TBG and albumin concentrations, so that the free-T4 index based on the AT3U ratio and T4 may be more useful than the CT3U method for evaluating free-T4 concentrations in low-T3 syndrome, which frequently has concomitant decreases in TBG and albumin concentrations. PMID- 3096614 TI - Automated determination of apolipoprotein AI and apolipoprotein E in cerebrospinal fluid. PMID- 3096615 TI - Multiple myeloma with serum IgM kappa and Bence Jones lambda biclonal gammopathy. AB - We report a rare finding: IgM kappa and Bence Jones lambda double gammopathy in serum of a 80-year-old man with untreated symptomatic multiple myeloma. The unusual findings are confined to the laboratory studies demonstrating also a Bence Jones lambda proteinuria, high erythrocyte sedimentation rate (113 mm/h), and anemia. The synthesis of the different light chains seems to occur in separate cellular clones. PMID- 3096616 TI - The pathology of diabetic neuropathy and the effects of aldose reductase inhibitors. PMID- 3096618 TI - Thoughts on the epidemiology of diverticular disease. PMID- 3096617 TI - Cataract and retinopathy: screening for treatable retinopathy. AB - Diabetes causes cataract and certain physical changes in the lens. The diabetic lens is larger than the non-diabetic and shows greater light scatter and fluorescence. Both hyperglycaemia and lowering of blood glucose case refractive changes and hypermetropia is the most common. Classical 'snow-flake' juvenile cataract associated with hyperglycaemia is now rare. It has an osmotic mechanism. Diabetes is a risk factor for cataract in adults which is duration dependent, more frequent in women and leads to earlier surgery. It resembles non-diabetic senile cataract. Extracapsular cataract extraction is the method of choice for diabetic cataract with a better visual result and less risk of rubeosis iridis. A posterior chamber implant may still permit retinal photocoagulation if necessary. Diabetic retinopathy is still the leading cause of blindness in the working age group. The beneficial effect of photocoagulation has been shown by randomized controlled trials to be long-lasting for both proliferative retinopathy and maculopathy. Therefore there is a need for screening, especially for those with proliferative disease which may be present without symptoms. A knowledge of risk factors will enhance detection rate with duration as the strongest determinant for retinopathy. Any screening modality should be highly sensitive as well as specific. The role of different professionals as potential screeners should be considered. Adequate provisions include facilities for checking vision and for dimming ambient lighting. Mydriasis and a good ophthalmoscope light will increase detection rate. The use of a 45 degrees non-mydriatic camera is unlikely to supplant the use of an ophthalmoscope as a single field is likely to miss important lesions. A 60 degrees camera may confer a large enough field and the use of transparencies will provide magnification when films are projected but the camera is more difficult to use. A list of features chosen by a recent study to characterize sight-threatening retinopathy is included and their presence indicates the need for referral to an ophthalmic clinic for treatment or close observation. PMID- 3096619 TI - Analysis of isolated and combined effects of calcium ionophore and phorbol ester on T lymphocyte activation. AB - Isolated and combined effects of the calcium ionophore A23187 and of the protein kinase C activator phorbol myristate acetate (PMA) on T cell activation parameters were analysed on unprimed Balb/c lymph node T lymphocytes (LNL). High doses of PMA were mitogenic for resting T cells, but non-mitogenic doses of PMA induced T cell proliferation in combination with A23187, which was non-mitogenic by itself. Mitogenesis induced by a combination of A23187 and PMA (A23187/PMA) showed the following characteristics: it was not abolished after extensive depletion of accessory cells; purified L3T4+, but not Lyt2+ T cells responded in the absence of accessory cells; mitogenesis was completely blocked by a mixture of two monoclonal antibodies directed to the murine interleukin 2 (IL-2) receptor (7D4/3C7mAbs); cyclosporin A, dibutyril cyclic AMP, and T cell K+ channel blockers quinine and verapamil all blocked mitogenesis. A marked synergism between A23187 and PMA was noted in induction of T cell enlargement, IL-2 release, and induction of IL-2 responsiveness. No synergism was noted in IL-2 receptor expression, A23187 and PMA being able to induce IL-2 receptors alone. Calcium ionophore induced IL-2 receptor expression, but failed to induce IL-2 release and IL-2 responsiveness. Addition of A23187/PMA to the IL-2-dependent CTL L clone did not result in cell proliferation. Addition of A23187/PMA to Con A activated T cell blasts leads to a vigorous proliferative response. This response is blocked by 7D4/3C7 mAbs, indicating a role for endogenously produced IL-2 in this case. The results indicate that T cell mitogenesis by A23187/PMA is IL-2 dependent, and suggest a critical role for protein kinase C in IL-2 release and induction of IL-2 responsiveness. In addition, the data suggest distinct, but co operative pathways of IL-2 receptor induction, controlled by elevated Ca2+ alone and by protein kinase C. Subsequent intracellular events of T cell activation by A23187/PMA may be quite similar to those triggered by Con A, since both kinds of stimulation are blocked by agents such as cyclosporin A, dbcAMP and K+ channel blockers. PMID- 3096621 TI - Infection and transfusion therapy in acute leukaemia. AB - Granulocytopenia is the single most important risk factor for infection in patients with acute leukaemia. There are limitations to the effective prophylaxis of infection in granulocytopenic patients, but practical measures include the management of the patient in a private hospital room, the requirement of all medical personnel and visitors to wash their hands carefully and to wear masks, restricting the patient to a low-bacteria diet devoid of fresh fruit, vegetables and salads, and the administration of oral antimicrobial agents for gastrointestinal decontamination. When fever develops, empirical therapy with a combination of an aminoglycoside plus an antipseudomonal beta-lactam should be started promptly. A double beta-lactam combination of cefoperazone or ceftazidime plus piperacillin can be substituted if nephrotoxicity is a concern. The addition of empirical intravenous amphotericin may be useful in patients who remain febrile and granulocytopenic on broad-spectrum antibiotics, especially if surveillance cultures indicate fungal colonization. Amphotericin is also the most reliable agent for the treatment of established fungal infections. Acyclovir is not recommended for prophylaxis in acute leukaemia patients but should be reserved for the treatment of well-documented and clinically significant herpes simplex viral infections. During periods of remission, most patients with AML remain free of infection except when they become granulocytopenic again during intensification or consolidation chemotherapy. On the other hand, children with ALL in remission may experience frequent infections unrelated to granulocytopenia as a consequence of their maintenance chemotherapy. Pneumocystis carinii, varicella zoster, and other viruses are common pathogens. Trimethoprim sulphamethoxazole is effective prophylaxis against Pneumocystis carinii pneumonia in patients with ALL, while intravenous acyclovir is the drug of choice for treatment of varicella zoster infection. Transfusion therapy in the acute leukaemia patient is guided by the patient's peripheral blood counts and degree of sensitization to blood products. Generally, packed red blood cells are given in order to maintain the haematocrit at greater than 30%, while random-donor platelets are administered to keep the platelet count at greater than 20 X 10(9)/l. If refractoriness to platelet transfusions develops, HLA-matched platelets from family members or selected unrelated donors can be used. Similarly, washed or filtered red blood cells may be given to patients with previous and recurrent non-haemolytic febrile reactions to red blood cell transfusions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3096620 TI - Biochemical aspects of acute leukaemia. PMID- 3096622 TI - Oscillation of intracranial pressure and sleep. PMID- 3096624 TI - Pharmacokinetics of CaNa2EDTA and chelation of lead in renal failure. AB - The pharmacokinetics of 1 gm intramuscular doses of CaNa2 (14C-)EDTA and the chelation of lead (Pb) were studied in 10 subjects with varying degrees of renal function and normal body burdens of Pb. The clearance of CaNa2EDTA significantly correlated with creatinine clearances (CLCR) (r = 0.8373; P = 0.0097). Clearances were decreased in subjects with CLCR less than 70 ml/min as compared with subjects with CLCR greater than 100 ml/min (28 vs. 76 ml/min). Maximum serum CaNa2EDTA concentrations and volume of distribution (Varea) (0.05 to 0.23 L/kg) were similar in all subjects. The Varea is smaller than previously described and is more consistent with other experimental data. Considering all subjects, initial blood Pb concentrations correlated with cumulative urine Pb excretion over 3 days (r = 0.8967; P = 0.0005). Urine Pb excretion did not correlate with measures of renal function or measures of CaNa2EDTA kinetics. Subjects with abnormal CLCR showed significantly greater decreases in blood Pb from day 1 to day 4 (7.0 micrograms/dl vs. 1.2 micrograms/dl) compared with normal subjects. These decreases in blood Pb correlated with CLCR (r = 0.7774; P = 0.138) and urine protein (r = 0.8435; P = 0.0087) but not with urine Pb excretion. Renal dysfunction may alter Pb chelatability, bone-blood Pb reequilibration, PbEDTA distribution, or PbEDTA excretion. PMID- 3096623 TI - The effect of intravenous, subcutaneous, and intranasal GH-RH analog, [Nle27]GHRH(1-29)-NH2, on growth hormone secretion in normal men: dose-response relationships. AB - A 29 amino acid analog of growth hormone releasing hormone (GH-RH)-40 was given intravenously, subcutaneously, and intranasally to normal men to determine its effectiveness in stimulating growth hormone (GH) release. The GH-RH analog, [Nle27]GH-RH(1-29)-NH2, is an amidated 29 amino acid peptide that has one amino acid substitution at position 27. This peptide stimulates GH secretion when given by the intravenous, subcutaneous, and intranasal routes without adverse effect. The degree of GH stimulation was variable among subjects and the greatest amount of stimulation occurred with the highest doses. GH stimulation occurred in a dose responsive manner after all three routes of administration. A tenfold higher subcutaneous dose was required to stimulate a comparable amount of GH secretion as compared with intravenous administration, and a thirtyfold higher intranasal than intravenous dose was required to stimulate approximately one fifth the amount of GH release. For comparison, one dose of GH-RH-40, 1 microgram/kg, was administered intravenously. GH secretion after 1 microgram/kg GH-RH-40 and 1 microgram/kg Nle27 GH-RH was comparable between the two groups of subjects. Stimulation of GH secretion by Nle27 GH-RH occurred within 5 minutes of intravenous and within 10 minutes of subcutaneous and intranasal administration; peak GH levels were observed within 30 minutes. GH levels declined and returned to near baseline levels 2 hours after administration of the analog.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096625 TI - Similarities between the insulin-like stimulatory effect of human IgG and NSILP. AB - Since the insulin-like stimulatory effect of human IgG on adipocyte lipogenesis, exerted through its Fc moiety, is not neutralized by anti-insulin antisera, IgG may contribute significantly to the non-suppressible insulin-like activity (NSILA) of plasma. 91% of NSILA has been shown previously to be associated with a high mol. wt. protein (NSILP). The purpose of this investigation was to assess whether IgG and NSILP have similar stimulatory effects on adipocyte lipogenesis and whether this effect can be neutralized by preincubation with gamma-chain specific anti-IgG antiserum; whether IgG stimulates 35S-sulphate uptake by porcine cartilage, known to be stimulated by insulin-like growth factors but not NSILP; and whether gamma-chain specific anti-IgG antisera precipitate IgG in a fashion similar to that with IgG preparations. Our investigations show that both IgG and NSILP have similar dose response relationships with respect to the stimulation of adipocyte lipogenesis and that both lose their adipocyte stimulating effect following preincubation with anti-IgG antiserum; neither IgG nor NSILP stimulate 35S-sulphate uptake by porcine cartilage, unlike serum somatomedin and crude NSILA-s preparations; and that gamma-chain specific anti IgG antisera form precipitin lines with NSILP. Therefore, NSILP and IgG molecules have immunological and biological similarities; there may occur a homology between the Fc fragment of IgG and the NSILP molecule. PMID- 3096626 TI - Effects of aurothioglucose and auranofin on radiographic progression in rheumatoid arthritis. AB - Radiographic films of 40 patients participating in a single centre patient blind study of auranofin versus aurothioglucose were evaluated in a random order by one reader. The two treatment groups were comparable with respect to number of erosions and total radiographic score at the start of the study. Only in the auranofin-treated patients was a statistically significant increase in the mean number of new erosions (p less than 0.001 at 6 months and p less than 0.01 at 12 months treatment, paired t-test) as well as in the total radiographic score (p less than 0.01 at 6 and 12 months treatment, paired t-test) observed. Results of this study confirm that parenteral gold compounds do retard radiographic progression of joint destruction in the treatment of rheumatoid arthritis. The effects on radiographic progression shown in this study are in agreement with other reports which, based on clinical and biochemical parameters, have shown that auranofin is somewhat less effective than the injectible gold salts. PMID- 3096627 TI - Nonfatal bacteremia caused by a mucoid, alginate-producing strain of Pseudomonas aeruginosa. AB - The first case of mucoid Pseudomonas aeruginosa bacteremia is reported in a hospitalized 78-yr-old woman with drug-induced hepatitis attributed to antituberculous therapy. The bacteremia was successfully treated with tobramycin and carbenicillin. Furthermore, the extracellular material of this mucoid strain was extracted, purified, and characterized as an alginate of high molecular weight, similar to that of mucoid Pseudomonas aeruginosa strains from cystic fibrosis. PMID- 3096628 TI - Facilitated detection of antibiotic-resistant Pseudomonas in cystic fibrosis sputum using homogenized specimens and antibiotic-containing media. AB - Sputa from 30 patients with cystic fibrosis (CF) were cultured on routine and selective media plus three Mueller-Hinton antibiotic resistance screening plates containing tobramycin (5 micrograms/ml), azlocillin (100 micrograms/ml), and ticarcillin (100 micrograms/ml). In addition to direct semiquantitative plating, samples were homogenized for semiquantitative and quantitative culture. Blood agar plates from direct semiquantitative and homogenized semiquantitative cultures were then replica plated onto the antibiotic screening plates. Homogenized semiquantitative and quantitative cultures both detected more Pseudomonas aeruginosa strains than direct semiquantitative plating (103 versus 85 strains), including more antibiotic-resistant strains. Antibiotic screening media facilitated isolation of resistant strains and decreased detection time by 24 hr. Of the 103 strains on homogenized semiquantitative and quantitative cultures isolated before replica plating, 13 (13%) were tobramycin-resistant, 67 (65%) were ticarcillin-resistant, and 42 (41%) were azlocillin-resistant; 13 of 30 cultures (43%) had at least one tobramycin-resistant organism before replica plating. Replica plating detected an additional seven tobramycin-resistant and nine ticarcillin- or azlocillin-resistant strains in seven patients. Homogenization, antibiotic screening media, and replica plating enhance recognition of antibiotic-resistant strains in CF sputum. PMID- 3096629 TI - In vitro activity of CI-934, a new quinolone antimicrobial, against gram-positive bacteria. AB - The in vitro activity of CI-934, a new quinolone antimicrobial, was compared with that of ciprofloxacin against selected gram-positive bacteria. Concentrations of CI-934 required to inhibit 90% of strains (MIC90) were twofold to eightfold lower than those of ciprofloxacin. With the exception of Streptococcus faecium, all isolates were inhibited by CI-934 at concentrations less than or equal to 1.0 microgram/ml. PMID- 3096630 TI - Biochemical and immunological studies of bovine and porcine neurofilament triplet proteins by peptide mapping after cyanogen bromide cleavage. AB - Peptide mapping of the three bovine and porcine neurofilament protein subunits ("L", "M" and "H") with apparent mol. wts of 70, 160 and 210 kDa were performed with CNBr, leading to the cleavage of methionyl bonds. We have obtained two characteristic large fragments with molecular weights of 85 kDa for the "M" bovine subunit and 135 kDa for the "H" subunit of bovine neurofilament. A comparison of the electrophoretic patterns of CNBr generated polypeptides of "L" subunit from beef and pig showed that they are highly related structures. The peptide mappings of CNBr peptides of "M" and "H" subunits from beef and pig were significantly different. Antibodies were raised against the 85 kDa and 135 kDa CNBr fragments. Immunoblotting results with anti-85 kDa and anti-135 kDa of beef are in favour of large differences of structure between the "M" subunits from pig and beef. The "H" proteins were very similar and they also showed that the C terminal part of bovine "H" and "M" proteins share common antigenic determinants. PMID- 3096631 TI - Does vitellogenin inhibit lipoprotein lipase in the laying hen? AB - Vitellogenin isolated from laying-hen plasma strongly inhibited chicken adipose tissue lipoprotein lipase in vitro, but inhibition was reduced or prevented by Ca2+ and Mg2+ ions and by partial dephosphorylation. Plasma from blood collected from laying hens using EDTA as anticoagulant was a potent inhibitor of lipoprotein lipase, but serum from laying hen blood caused inhibition only when dilute or after addition of EDTA. Heparin reduced or abolished the inhibition of lipoprotein lipase by plasma, serum and purified vitellogenin. The results suggest that inhibition of lipoprotein lipase by vitellogenin requires the presence of charged phosphate groups on vitellogenin and an unoccupied heparin binding site on the enzyme. Neither condition is likely to occur in the laying hen in vivo. PMID- 3096632 TI - Does sodium cromoglycate have an effect on contact dermatitis? AB - Sodium cromoglycate was applied to the forearm of 9 subjects with known delayed hypersensitivity, and to the back of 14 dinitrochlorobenzene-sensitized guinea pigs before challenge with the allergen and sodium lauryl sulphate. Sodium cromoglycate did not decrease the intensity of allergic of toxic-irritant reactions in either humans or guinea pigs. PMID- 3096634 TI - The relative bioavailability of levonorgestrel and ethinyl estradiol administered as a low-dose combination oral contraceptive. AB - The relative bioavailability of levonorgestrel (LNG) and ethinyl estradiol (EE) administered concomitantly both as an oral tablet and as a solution was assessed in a randomized two-period crossover study in 24 healthy women. Serum concentrations were monitored for 96 h after each administration. The relative bioavailability (Fr) of LNG in the tablet with respect to the solution was 107%; thus the two formulations were bioequivalent with respect to LNG. The relative bioavailability of EE, however, was significantly lower for the tablet (Fr 83%) compared to the solution. This difference may have been due to either decreased absorption or enhanced presystemic elimination of EE from the tablet formulation. PMID- 3096633 TI - Progestins and oral contraceptive-induced lipoprotein changes: a prospective study. AB - In order to determine the effects on plasma lipoproteins of oral contraceptives containing progestins with varying androgenic potency, 136 healthy women were randomized into 3 groups and followed prospectively for one year while receiving either 50 mcg ethinyl estradiol and 1.0 mg ethynodiol diacetate (EED), 50 mcg ethinyl estradiol and 1.0 mg norethindrone acetate (ENA), or 50 mcg ethinyl estradiol and 0.5 mg d-1 norgestrel (ENG). Comparison was made to a self-selected group of 50 women using alternative means of contraception. Plasma cholesterol increased by 7-9% and triglycerides by 32-57% in all 3 groups (p less than 0.05). ENG use resulted in other significant lipoprotein changes including an 18% increase in low density lipoprotein cholesterol (LDL-C), a 13% fall in high density lipoprotein cholesterol (HDL-C) and a 27% decline in HDL2 cholesterol (HDL2-C) (p less than 0.05). Apoprotein A-I (Apo A-I) increased by 9% with ENA and by 11% with EED (p less than 0.05), but did not change significantly with ENG. This prospective study demonstrates that in oral contraceptive agents with identical estrogen, progestins with different androgenic potency produce major and different changes in plasma lipoproteins. PMID- 3096635 TI - Pharmacodynamic effects of levonorgestrel (LNG) administered either orally or subdermally to early postpartum lactating mothers on the urinary levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) in their breast-fed male infants. AB - Pharmacodynamic effect of levonorgestrel (LNG) present in small amounts in infant's circulation has not yet been studied adequately. In our present study, nine women were taking oral minipills (LNG 30 micrograms daily) and 10 were using subdermal implants, Norplant(R)-2, during early postpartum period from four weeks to 15 weeks. These were healthy lactating women in age group 20 to 35 yrs, who had full-term normal delivery of male infants. Daily 4-hour urine samples (from 8 AM to 12 noon) were collected from four weeks onwards to 15 weeks for estimations by radioimmunoassays of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels. No significant differences (P greater than 0.05) were found between geometric means of the total area under curve at weekly intervals for FSH, LH and T hormones between the male infants from control group (n=10) when compared with oral minipill or Norplant(R)-2 users. These results are reassuring for future sexual growth and development of children who are exposed to contraceptive steroids during their infancy; however, they do require further confirmation by long-term epidemiological studies incorporating monitoring and surveillance of such children. PMID- 3096636 TI - A lung model of carbon dioxide concentrations with mechanical or spontaneous ventilation. AB - Modifications of a commercially available mechanical lung model (Vent-Aid Training Test Lung, Michigan Instruments, Inc., Grand Rapids, MI) enabled the study of CO2 concentration, distribution, and washout curves. An additional modification allowed either simultaneous or separate study of spontaneous ventilation and work of breathing. PMID- 3096637 TI - Clinical significance of hypercholesterolemia and hyponatremia. PMID- 3096638 TI - Aldose reductase localization in dog retinal mural cells. AB - The selective degeneration of retinal mural cells, a hallmark of early human diabetic retinopathy, has also been reported to occur in both diabetic and galactose-fed dogs. By employing antibodies raised against purified dog lens aldose reductase the presence of aldose reductase can be immunohistochemically demonstrated in the cytoplasm of mural cells but not endothelial cells of dog retinal vessels isolated by trypsin digestion. This immunohistochemical staining is similar to that observed with isolated human retinal vessels. PMID- 3096639 TI - Ocular chrysiasis: accumulation of gold in the rabbit eye. AB - Gold entered the eye and was accumulated in the aqueous humor, iris-ciliary body, and cornea (measured by flameless atomic absorption spectroscopy) of rabbits given gold sodium thiomalate by subcutaneous infusion for 4 weeks. It was not detected following such exposure in the vitreous humor, lens or retina. The concentration of gold in the cornea was quite high, about 25% of that in the liver. The concentration in the aqueous humor was only about 2.5% of that in the plasma, which is similar to the fraction of gold (5%) that is not bound to plasma proteins. PMID- 3096640 TI - Physiology and pathophysiology of colloid osmotic pressure and albumin metabolism. PMID- 3096641 TI - Iatrogenic myocardial edema with crystalloid primes. Effects on left ventricular compliance, performance, and perfusion. PMID- 3096642 TI - An evolutionary conserved early replicating segment on the sex chromosomes of man and the great apes. AB - Replication studies on prometaphase chromosomes of man, the chimpanzee, the pygmy chimpanzee, the gorilla, and the orangutan reveal great interspecific homologies between the autosomes. The early replicating X chromosomes clearly show a high degree of conservation of both the pattern and the time course of replication. An early replicating segment on the short arm of the X chromosomes of man (Xp22.3) which escapes inactivation can be found on the X chromosomes of the great apes as well. Furthermore, the most early replicating segment on the Y chromosomes of all species tested appears to be homologous to this segment on the X chromosomes. Therefore, these early replicating segments in the great apes may correspond to the pseudoautosomal segment proposed to exist in man. From further cytogenetic characterization of the Y chromosomes it is evident that structural alterations have resulted in an extreme divergence in both the euchromatic and heterochromatic parts. It is assumed, therefore, that, in contrast to the X chromosomes, the Y chromosomes have undergone a rapid evolution within the higher primates. PMID- 3096643 TI - Transdermal nitroglycerin (Transiderm-Nitro) in the treatment of unstable angina pectoris. AB - Eighteen patients, 13 male and five female, with unstable angina pectoris and who had greater than or equal to 3 anginal attacks/day despite treatment with beta- and/or Ca-blockers were treated for three days with transdermal nitroglycerin (Transiderm-Nitro 25 mg/24 hours) in a randomised, placebo-controlled trial. A significant reduction of anginal attacks (p = 0.03) was demonstrated only during the first day of treatment. The lack of significant effects during the following two days was ascribed partly to the possible development of nitrate-tolerance, partly to a declining number of anginal attacks in the placebo-group during the trial period, for which reason the difference between the actively treated and the placebo group became smaller and finally the consumption of nicomorphine was considerably greater in the placebo group. PMID- 3096645 TI - Diffusing capacity measurement in patients with airway obstruction. PMID- 3096644 TI - Community-acquired pneumonia caused by mixed aerobic bacteria. AB - Mixed bacterial pneumonia caused by organisms other than anaerobes has been infrequently reported. We describe six cases and review the literature. Two patients had co-infection with S pneumoniae and L pneumophila. Two were infected with S pneumoniae and K pneumoniae and the others simultaneously harbored M tuberculosis and N asteroides. The first two sets of patients had bacteria isolated from usually sterile sites (blood and lung), while the latter harbored repeatedly isolated organisms not usually felt to be part of the normal respiratory flora. Mixed infection may help explain the substantial mortality still seen from pneumonia. This is especially true if Legionella, mycobacteria, or Nocardia species are encountered where routine smears and cultures may not aid in the diagnosis. Poor clinical response to specific antibacterial therapy in pneumonia should trigger further investigation for other potential pathogens. PMID- 3096646 TI - [Pseudoscopic vision in binocular fundus observation and its correction]. PMID- 3096647 TI - [A dynamic schematic eye for close work]. PMID- 3096648 TI - [A new method for the quantitative representation of anisometropia]. PMID- 3096649 TI - [A nomograph for estimating the effective power of crossed cylindric lenses]. PMID- 3096650 TI - [Conversion between E-shape and C-shape optotypes]. PMID- 3096651 TI - [A visual test chart of figures for preschool children]. PMID- 3096652 TI - [Asthenopia and aniseikonia in anisometropic patients]. PMID- 3096653 TI - [Effects of sympathomimetics on residual accommodation in atropinized eyes]. PMID- 3096654 TI - [Traumatic recession of the anterior chamber angle and secondary open-angle glaucoma]. PMID- 3096655 TI - [Fuchs' syndrome and glaucoma]. PMID- 3096656 TI - [Corticosteroid glaucoma]. PMID- 3096657 TI - [Clinical analysis of 417 orbital operations]. PMID- 3096658 TI - [Clinical significance of tear lysozyme activity in herpes simplex keratitis]. PMID- 3096659 TI - [Numerical analysis of intubation dacryocystography of the normal lacrimal drainage system]. PMID- 3096660 TI - [Physiologic values of ocular refraction in Chinese preschool children]. PMID- 3096661 TI - [Pigmented basal cell carcinoma of the eyelid]. PMID- 3096662 TI - [Problems in the diagnosis of meibomian gland carcinoma of the eyelid]. PMID- 3096663 TI - [Orbital meningioma]. PMID- 3096664 TI - [Orbital chloroma]. PMID- 3096665 TI - [Duro-cavernous red-eyed shunt syndrome]. PMID- 3096666 TI - [Nanophthalmos]. PMID- 3096667 TI - [Analysis of misdiagnosed mucoceles of the nasal sinuses]. PMID- 3096668 TI - [Photo-chemical therapy in the treatment of basal cell carcinoma of the eyelid]. PMID- 3096669 TI - [Indirect injury of the intracanalicular portion of the optic nerve]. PMID- 3096670 TI - [Standards for the vitality of endothelial cells in donor grafts for penetrating keratoplasty]. PMID- 3096671 TI - [Determination of serum IgE in vernal conjunctivitis patients]. PMID- 3096672 TI - Improved high-affinity monoclonal antibody to iododeoxyuridine. AB - Three monoclonal antibodies (Mabs), IU-1, IU-4, and B-44 were evaluated in enzyme immunoassays (ELISA) and by flow cytometry for their abilities to recognize bromodeoxyuridine (BrdUrd)- and iododeoxyuridine (IdUrd)-substituted DNA's, nucleotides, and nucleosides. IU-4 is a new Mab, derived from mice immunized with 5-iodo-2'-deoxyuridine-5'-monophosphate (IdUMP) conjugated (IdUMP) conjugated through the phosphate group to albumin. This immunogen was selected to resemble IdUMP in DNA. In competition ELISA assays, IU-4 prefers IdUrd to BrdUrd and prefers halogenated nucleotides over the corresponding nucleosides. In both ELISA and flow analysis, IU-4 recognizes IdUrd in DNA at substitution frequencies at least as low as one IdUrd one per 1,000 normal bases. The high affinity of IU-4 for IdUrd-DNA contrasts with IU-1 and B-44, which show a strong binding dependency on the frequency of base substitution and require DNA that is essentially fully substituted with BrdUrd for binding in both flow and ELISA assays. The high affinity of IU-4 for IdUrd in DNA and its independence of IdUrd residue spacing make it a superior reagent for the quantitative labeling of halogenated thymidine analogues in whole cells. PMID- 3096673 TI - Cell-by-cell autofluorescence correction for low signal-to-noise systems: application to epidermal growth factor endocytosis by 3T3 fibroblasts. AB - Autofluorescence of cells can be a major portion of the fluorescence signal in many systems, especially when fluorescent conjugates are used to study receptor ligand systems for which there are less than 70,000 receptors per cell. We have devised a method for the cell-by-cell correction of autofluorescence for flow cytometric data by using an additional parameter to measure and correct for autofluorescence in the fluorescence channel. The principle has been extended to allow simultaneous correction for autofluorescence and dual-fluorescence spillover compensation in samples labeled with two different fluorochromes; all corrections were done in software, making them applicable to any flow cytometer. The autofluorescence correction method was used to analyze the acidification of epidermal growth factor (EGF) by Swiss 3T3 cells. EGF is acidified to pH 6.2 starting two min after labeling, with a half-time for acidification of 45 s. PMID- 3096674 TI - Pharmacokinetics of phenobarbitone in protein energy malnutrition. AB - Phenobarbitone kinetics was studied in malnourished and normal children after single oral dose of approximately 7.0 mg/kg. Estimation of serum phenobarbitone concentration was performed by spectrophotometric method. Elimination half-life was 58.9 +/- 9.5 h and 30.15 +/- 6.1 h for malnourished and healthy children, respectively. Compared to healthy children, tmax was prolonged in malnutrition group suggesting slow absorption in the latter group. The systemic bioavailability was observed to be higher in protein energy malnutrition. Modifications of the usual dosage regimen in malnutrition are recommended. PMID- 3096675 TI - Nutritional assessment of protein status. PMID- 3096676 TI - Isolation and nucleotide sequence analysis of a cloned cDNA encoding the beta subunit of bovine follicle-stimulating hormone. AB - Two different cDNAs containing sequences coding for the beta-subunit of bovine follicle stimulating hormone (FSH-beta) have been isolated from a phage lambda gt11 bovine pituitary cDNA library. The complete nucleotide sequence of both clones was determined, and the combined sequence represents most of FSH-beta mRNA. The combined sequence contains 46 nucleotides of 5'-untranslated sequence followed by 387 nucleotides of coding sequence. The coding sequence predicts a 19 amino-acid amino-terminal precursor segment followed by the 110-amino-acid sequence of mature bovine FSH-beta. The cDNA sequence demonstrates the presence of a long 3'-untranslated region containing 1295 bases followed by a segment representing the poly(A) portion of the mRNA. Thus, the combined sequence of the cDNAs suggests a minimal size of 1.7 kb for FSH-beta mRNA. Analysis of FSH-beta sequences present in bovine pituitary mRNA demonstrated the presence of an mRNA with a size of about 2.0 kb. This apparent discrepancy is probably due to the presence of a several-hundred nucleotide tract of poly(A) at the 3' terminus of the mRNA. Comparison of the amino acid sequence predicted from the cDNA with the known amino acid sequence of the beta-subunit of FSH from several different species demonstrates that the protein has been highly conserved. PMID- 3096677 TI - Molecular model of the interaction between the glucocorticoid receptor and the regulatory elements of inducible genes. AB - Binding sites for the glucocorticoid receptor in an ecdysone-inducible gene from Drosophila melanogaster and in the chicken vitellogenin gene are described. A comparison with other binding sites for the glucocorticoid receptor, which have been analyzed by methylation protection experiments, shows they can be classified into three groups. The first group exhibits two blocks of contact points in two subsequent turns of the DNA helix, and includes only functional regulatory elements. The second group shows an identical contact with the hexanucleotide 5' TGTYCT-3', but only half the contact points in the other turn of the helix, whereas the third group of sites exhibits only the contact points within the conserved hexanucleotide. An analysis of the hydrogen-bonding potential of the DNA base pairs along the major groove of 10 binding sites shows a very well conserved pattern and a twofold rotational symmetry, suggesting that the array of hydrogen bonds may be a relevant aspect of sequence recognition by hormone receptors. A representation of the binding sites and contact points by computer graphics suggests the interaction of a receptor dimer, in a head-to-head arrangement, with two subsequent turns of the B-DNA helix within the glucocorticoid regulatory elements. PMID- 3096678 TI - Effects of intratesticular islet transplantation on hepatic glycogen metabolism in the rat. AB - Pancreatic islet transplantation into cryptorchid testes resulted in near complete normalization of hepatic enzymic parameters associated with glycogen metabolism. Measurements of plasma glucose levels and of immunoreactive insulin levels indicated that islet transplantation also resulted in improved control of glycemia in diabetic animals receiving these grafts. Electron microscopic examination of cryptorchid testes revealed the presence of islet cells in the interstitial spaces outside of the seminiferous tubules. These islet cells both had granules identified as B granules by morphologic criteria and appeared to be actively secreting the contents of these granules. This site of islet transplantation appeared to provide a protected site which facilitated long-term survival and continued functioning of islet grafts. PMID- 3096679 TI - [Cholesterol esters as a substrate of animal lipoxygenases]. PMID- 3096680 TI - [Extramitochondrial Ca2+ controls the activity of the Ca2+-transporting system in mitochondria]. PMID- 3096682 TI - [Gamma interferon in psoriasis arthropathica]. PMID- 3096681 TI - Diazepam and methadone blood levels following concurrent administration of diazepam and methadone. AB - Results of a previous study indicated that the opioid effects of methadone were enhanced by the concurrent administration of diazepam in methadone-maintained subjects. To determine whether a pharmacokinetic interaction might account for this methadone-diazepam interaction, the plasma levels of methadone, diazepam and diazepam metabolites were determined in blood samples collected during that study. Five adult male patients on methadone maintenance (50-60 mg/day) were administrated single doses of placebo, diazepam (20 and 40 mg), methadone (100%, 150% and 200% of the maintenance dose), and four diazepam-methadone dose combinations (20 and 40 mg diazepam in combination with 100% and 150% of the maintenance dose). The results showed that the concurrent administration of methadone and diazepam did not significantly change the time-course or areas under the plasma concentration-time curve of methadone, diazepam or N-desmethyl diazepam compared to the levels following the administration of either drug alone. Thus, plasma drug level analysis does not indicate a pharmacokinetic interaction between diazepam and methadone. PMID- 3096683 TI - [Protracted hypoglycemia as a consequence of the secret taking of glibenclamide by a young female diabetic]. PMID- 3096684 TI - [Delayed allergy following mesna]. PMID- 3096685 TI - [Differentiation of Sarcocystis muris and S. dispersa infections of the mouse using isoelectric focusing and immune assays]. PMID- 3096687 TI - The effect of cromolyn on nasal disease. PMID- 3096686 TI - Fluvoxamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. AB - Fluvoxamine is a new antidepressant which potently and specifically inhibits neuronal reuptake of serotonin. In the absence of other major pharmacological effects it appears that its antidepressant activity stems from facilitation of serotoninergic neurotransmission as a result of reuptake inhibition. Studies suggest that fluvoxamine has overall therapeutic efficacy comparable with that of imipramine and clomipramine in depressive illness. It causes fewer anticholinergic-type and cardiovascular side effects than the tricyclic antidepressants but it is associated with a higher incidence of nausea and vomiting. Elderly patients also respond well to fluvoxamine. Studies are now required to compare fluvoxamine with other second generation antidepressants and to establish whether some types of depressive illness respond more readily to fluvoxamine than other agents. Thus, in patients with depressive illness, fluvoxamine offers a suitable alternative to tricyclic antidepressants and may be especially valuable in patients with concomitant cardiovascular disease, and those unresponsive to or unable to tolerate tricyclic antidepressants. PMID- 3096688 TI - Status of human schistosomiasis on the eastern side of Kainji Lake area of Nigeria. PMID- 3096689 TI - Noninvasive monitoring of cardiorespiratory parameters. AB - Noninvasive methods for monitoring pH, pCO2 and pO2 have not achieved the original aim of providing a noninvasive, continuous assessment of arterial blood gases under all clinical conditions. Fingertip and ear oximeters provide measurement of oxygen saturation in arterial blood under most conditions, but accuracy is lost when intense peripheral vasoconstriction is present. Transcutaneous and conjunctival O2 and CO2 sensors also function as accurate trend monitors of PaO2 and PaCO2 in the hemodynamically stable patient. Measurement of pH by placement of a sensor into the subcutaneous tissue provides a continuous assessment of arterial pH in neonates with normal CO, but the use of these sensors in adult patients remains largely unproven. Noninvasive assessment of the adequacy of peripheral perfusion, cardiac function, and intravascular volume status can be performed using transcutaneous or conjunctival O2 and CO2 sensors. Early detection and correction of hypovolemia and diminished CO can be accomplished by monitoring tissue PO2 and PCO2. In the emergency department setting, in which the evaluation and initial treatment of critically ill patients often is performed by measurement of a limited set of physiologic parameters, the ability to evaluate tissue perfusion on a continuous basis is an important clinical advance. PMID- 3096690 TI - Prolactin messenger ribonucleic acid levels in the normal and hypogonadal mouse pituitary gland. AB - The effects of estrogen on the synthesis of pituitary PRL mRNA and PRL and the release of PRL into plasma were investigated in male and female normal and hypogonadal (hpg) mice. Because the hpg mouse is totally deficient in hypothalamic GnRH, it provides an excellent model for investigating the effects of estrogen and GnRH on PRL synthesis and release in the presence of a totally inactive gonadotropin-gonadal system. Estrogen stimulated the synthesis and release of pituitary PRL in both sexes of normal and hpg mice, and this marked increase in PRL synthesis correlated with an equally dramatic increase in pituitary PRL mRNA levels. Administration of GnRH alone produced a slight but significant increase in pituitary PRL content, which is consistent with an action of GnRH on prolactotropes, either directly or by way of a paracrine action involving gonadotropes. PMID- 3096691 TI - Thyrotropin-releasing hormone stimulation of prolactin secretion is coordinately but not synergistically regulated by an elevation of cytoplasmic calcium and 1,2 diacylglycerol. AB - The precise roles of the calcium and lipid pathways in TRH-stimulated PRL secretion from rat pituitary (GH3) cells are controversial. In particular, it is debated whether elevation of cytoplasmic free Ca2+ concentration [( Ca2+]i) is sufficient to cause burst secretion (0-2 min) or whether an increase in 1,2 diacylglycerol must accompany the Ca2+ elevation. In this study, the effects of TRH, which elevates 1,2-diacylglycerol, on [Ca2+]i and stimulation of burst secretion were compared with those of depolarization by high extracellular K+, which does not increase 1,2-diacylglycerol. A maximal concentration of TRH (1 microM) and depolarization by 17.5 mM K+ caused elevation of [Ca2+]i from the resting level of 140 +/- 20 nM to 470 +/- 70 nM and 514 +/- 60 nM, respectively, and stimulated burst secretion from 0.6 +/- 0.2 ng/10(6) cells/min to 3.3 +/- 0.8 and 3.1 +/- 0.4 ng/10(6) cells/min, respectively, when a small component of TRH stimulated secretion that is independent of elevation of [Ca2+]i was subtracted. A detailed comparison of multiple levels to which [Ca2+]i was elevated (up to 600 nM) and the degree of stimulation of burst phase secretion demonstrated the same positive linear correlation (correlation coefficient = 0.96) for TRH and K+ depolarization. Hence, elevation of [Ca2+]i is sufficient to cause burst secretion irrespective of elevation of 1,2-diacylglycerol. Optimal stimulation by TRH of sustained secretion of PRL did not depend on elevation of [Ca2+]i; sustained PRL secretion stimulated by 10 nM TRH was 2.6 +/- 0.4 and 2.7 +/- 0.2 ng/10(6) cells/min in control cells and arachidonic acid-pretreated cells in which [Ca2+]i was not elevated, respectively. The data from this and previous studies demonstrate that elevation of [Ca2+]i and 1,2-diacylglycerol may act coordinately, but not synergistically, to mediate TRH stimulation of PRL secretion from GH3 cells. PMID- 3096692 TI - Intracellular recordings from bovine anterior pituitary cells: modulation of spontaneous activity by regulators of prolactin secretion. AB - The electrophysiological properties of cultured bovine anterior pituitary cells were examined using intracellular recordings. Although all cells had high input resistances (mean 332 M omega), membrane potentials (Vm) showed a wide distribution (-32 to -80 mV). In 9 cells with low Vm (mean -38 mV) spontaneous Ca2+-dependent action potentials were observed (mean frequency 3.4 hertz). In the majority of silent cells (mean Vm -58 mV), application of TRH caused a reduction in membrane resistance and a transient hyperpolarization of Vm. This initial response was followed by a small, sustained depolarization. In 4/18 cells this depolarization led to the appearance of action potentials in previously silent cells. In 15/18 cells application of dopamine caused an increase in the membrane conductance and led to a sustained hyperpolarization of 30-35 mV. The response reversibly blocked the propagation of action potentials in spontaneously active cells. This effect could also be reversed by the dopamine receptor antagonists, sulpiride and haloperidol. In all cells, elevating the extracellular potassium concentration caused a concentration-dependent depolarization and decrease in the membrane input resistance. In some cells this effect was associated with an increased frequency of action potentials. Electrophysiological responses to TRH, dopamine, and elevated potassium were correlated with changes in the release of PRL. It is concluded that by their effects on Vm these factors modulate spontaneous electrical properties and may regulate the entry of calcium necessary for hormone secretion from lactotrophs. PMID- 3096693 TI - Energy metabolism in rat pituitary tumors during stimulation of prolactin by vasoactive intestinal polypeptide and thyrotropin-releasing hormone: a study with nuclear magnetic resonance spectroscopy. AB - The effect of the peptides TRH and vasoactive intestinal polypeptide (VIP) on phosphate-bound energy of GH3 tumor cells in vivo was investigated using the noninvasive technique of topical 31P-nuclear magnetic resonance spectroscopy. VIP (4.0 micrograms/100 g BW) caused a reduction in the high energy metabolite phosphocreatine and an increase in inorganic phosphate. In the same experiments (n = 9), VIP stimulated PRL secretion to a value of 146% +/- 13 of basal concentrations. The change in the inorganic phosphate-phosphocreatinine ratio had a positive correlation with the increase in PRL secretion (P less than 0.001), indicating a VIP-induced energy consumption for a process related to PRL secretion. In separate experiments, in vitro, it was confirmed that VIP increased energy consumption by demonstrating an increase in glycogenolysis by the pituitary tumor cells. TRH also increased PRL secretion to 145% +/- 23 of basal values but, in contrast, did not induce changes in energy metabolites detectable by nuclear magnetic resonance. It is concluded that VIP and TRH promote PRL release through different stages in the secretion process. PMID- 3096694 TI - Calcium-controlled secretion is effected through a guanine nucleotide regulatory protein in parathyroid cells. AB - Calcium regulates parathyroid secretion through mechanisms yet to be elucidated. We have investigated this phenomenon through use of pertussis toxin which catalyzes ADP-ribosylation and inactivation of a guanine nucleotide regulatory protein, possibly Ni or No. Calcium inhibition of PTH release is blocked in cells treated with pertussis toxin, and there is concomitant ADP-ribosylation of a 40 kilodalton protein. The ionophore A23187 inhibits secretion in toxin-treated as well as in control cells. We conclude that a guanine nucleotide regulatory protein is involved in calcium regulation of PTH secretion at a locus proximal to the intracellular site effecting inhibition of secretion. PMID- 3096695 TI - Differences in the carbohydrate moieties of the common alpha-subunits of human chorionic gonadotropin, luteinizing hormone, follicle-stimulating hormone, and thyrotropin: preliminary structural inferences from direct methylation analysis. AB - The carbohydrate components of combined alpha-subunits of urinary hCG and human pituitary LH (hLH), FSH (hFSH), and TSH (hTSH), each derived from the intact hormone, were studied by direct sugar analysis and methylation analysis. The methods provide a complete survey of the structural elements contained in the complex sugars associated with these glycoproteins, but do not establish the sugar sequences or anomeric configurations of glycosidic bonds. By analogy to N linked oligosaccharides that occur in many glycoproteins, the data suggest distinct structural features for carbohydrates of alpha-subunits combined with beta-subunits. hCG alpha contains biantennary asparagine-linked chains terminated by either NeuAc alpha 2-3Gal beta 1- or GlcNAc beta 1-2 Man alpha 1- and lacks fucose. hTSH alpha contains biantennary chains with the same termini as hCG alpha plus terminal R-O-4GalNAc and a fucosyl residue linked alpha 1-6 to the inner GlcNAc residue of the N-linked chitobiosyl core. hLH alpha may contain some high mannose chains, but primarily contains biantennary chains terminated by NeuAc alpha 2-3(6)Gal beta 1-, GlcNAc beta 1-, GalNac-1-, R'-O-6GlcNAc-1-, and R"-0 2Man-1-plus a fucosyl residue linked alpha 1-6 to the inner GlcNAc residue of the N-linked chitobiosyl core. hFSH alpha contains more complicated structures that probably include a bisecting GlcNAc residue linked beta 1-4 to a 3,6-di-O substituted core mannosyl residue, and terminal NeuAc alpha 2-3Gal beta 1-4(+/- Fuc alpha 1-3)GlcNAc-1, Gal beta 1-4(+/- Fuc alpha 1-3)GlcNAc-1-, R"'-O-GalNAc-1 , and GalNAc-1. In addition, the presence of 2,4-di-O-substituted mannose in hFSH alpha indicates that it contains triantennary chains. The identities of the R; R', R", and R"' groups were not determined, but recent studies of glycoprotein hormones suggest that they may be sulfate groups. Our results demonstrate differential glycosylation of virtually identical polypeptide hormone alpha subunits produced in the same organ or perhaps even in the same cell. PMID- 3096696 TI - The influence of chronic morphine treatment on the negative feedback regulation of gonadotropin secretion by gonadal steroids. AB - The influence of continuous stimulation of opiate receptors with morphine (M) on the negative feedback effects of testosterone (T), 5 alpha-dihydrotestosterone (DHT), and 17 beta-estradiol (E2) on LH and FSH secretion was studied in rats that had been castrated 2 weeks previously. In the absence of gonadal steroids, 4 days of continuous M exposure did not alter LH or FSH levels. Similarly, Silastic capsules containing crystalline T (5 mm) or E2 [5 mm long (75 micrograms E2/ml) to 7.5 mm long (300 micrograms E2/ml)] alone had little effect on LH or FSH release. However, in M-exposed rats, T reduced serum LH by greater than 90%, and E2 reduced LH by more than 75%. Among the doses of DHT evaluated, only the highest dose (7.5-mm Silastic capsules packed with crystalline DHT) reduced LH secretion, and M exposure only slightly enhanced this suppression. M or gonadal steroids alone produced little change in FSH levels in castrated rats. However, the combination of M plus E2 or DHT further reduced FSH levels. Evaluation of pituitary responses to LHRH revealed that when administered alone, T did not alter, DHT reduced, and E2 enhanced the LH response to the decapeptide. Neither M treatment alone nor M plus T or DHT altered the pituitary LH response to LHRH. On the other hand, M appeared to enhance the stimulatory effects of E2 on pituitary responsiveness to LHRH. These findings suggest that the interaction of M and gonadal steroids at the level of the pituitary could not explain the observed marked suppression of gonadotropin secretion by suboptimal T or E2 during opiate receptor stimulation with M. Collectively, these observations are in accord with the view that endogenous opioid peptides may play a role in modulating the sensitivity of the hypothalamus to the negative feedback effects of gonadal steroids. PMID- 3096697 TI - Transmembrane signals mediating neural peptide secretion: role of protein kinase C activators and arachidonic acid metabolites in luteinizing hormone-releasing hormone secretion. AB - The present experiments were designed to determine the effects of different activators of protein kinase C on the secretion of LHRH from median eminence nerve terminals incubated in vitro. The release of prostaglandin E2 (PGE2), a metabolite of arachidonic acid intimately involved in the secretion of LHRH, was also evaluated. Synthetic diacylglycerol [1,2-didecanoylglycerol (DiC10)] significantly enhanced PGE2 release in a concentration-dependent manner. Blockade of phospholipase A2 (PLA2) activity nullified this effect. LHRH release, on the other hand, was not increased by DiC10. However, in the presence of a lipoxygenase inhibitor, DiC10 produced a concentration-related increase in LHRH release, which paralleled that in PGE2. Phospholipase C (PLC) increased both PGE2 and LHRH secretion. Again, blockade of the lipoxygenase pathway enhanced the release of LHRH by PLC without affecting the stimulated secretion of PGE2. A phorbol ester, phorbol 12,13-dibutyrate (PDBu), markedly increased LHRH secretion while inducing a modest increase in PGE2 release. Both effects of PDBu were unaffected by lipoxygenase inhibition. DiC10, PDBu, and PLC significantly augmented LHRH secretion from tissues in which metabolism of arachidonic acid had been prevented by inhibition of both cyclooxygenase and lipoxygenase pathways, suggesting that activation of protein kinase C, independent of PLA2 activation, can lead to the secretion of this neural peptide. Some lipoxygenase metabolites had either no effect on [5- and 15-hydroxyeicosatetraenoic (5- and 15-HETE)] or induced a marginal stimulation of (12-HETE) LHRH release. At certain concentrations, 12-HETE enhanced the stimulatory effect of the phorbol ester on LHRH release. Our results suggest that activation of protein kinase C can stimulate LHRH secretion from nerve terminals in vitro and, further, that diacylglycerol may represent an important intracellular messenger participating in the events leading to LHRH secretion. In addition, stimulation with DiC10 and PLC uncovered inhibitory [unknown arachidonic acid metabolite(s) via lipoxygenase] and stimulatory (PGE2 via cyclooxygenase) pathways through with arachidonic acid metabolites may participate in the intracellular transduction of signals modulating neural peptide secretion. PMID- 3096698 TI - Immunofluorescent probing of the mitochondrial cholesterol side-chain cleavage cytochrome P-450 expressed in differentiating granulosa cells in culture. AB - Mitochondria in follicular cells from rat ovaries were visualized in culture by indirect immunofluorescence staining of cholesterol side-chain cleavage cytochrome P-450 (P-450scc). The confinement of the immunofluorescence in the conspicuous mitochondria allowed the design of a very sensitive and quantitative assay to study the modulated expression of the cytochrome in primary cultures of granulosa cells. (1) The induction of P-450scc synthesis was totally dependent upon treatment with FSH. Up to 85% of the cells became immunofluorescently labeled in the presence of FSH, and its induced P-450scc synthesis was inhibited by cycloheximide and alpha-amanitin. The induction of FSH was dose dependent (Kmapp = 35 ng/ml) and time dependent. Prolonged incubation with FSH maintained the high levels of the cytochrome content, despite a desensitized steroidogenic response which developed after 60 h of incubation with FSH. Prolonged FSH treatment also resulted in morphological changes in the induced mitochondria, which became fragmented and globular. (2) Inoculum densities, probably by altering cell shape, substantially affected the extent of P-450scc induction; this was suppressed (80%) at lower culture densities. (3) The immunofluorescent staining also revealed various degrees of cellular competence to express P 450scc. Within a single induced cell, all mitochondria emitted a similar fluorescent signal, but the degree of fluorescence per mitochondrion varied with different cells. The cell-specific information gained by the immunofluorescent technique also allowed the detection of ovarian interstitial cells that slightly contaminate the granulosa cell preparations. Unlike granulosa cells, interstitial cells express and maintain high levels of P-450scc without the need for hormonal induction. PMID- 3096699 TI - Calcium-calmodulin-dependent protein kinase in hyperplastic human parathyroid glands. AB - The function of the parathyroid gland is closely linked to intracellular and extracellular Ca2+ concentrations. As a step toward understanding the mechanism of action of Ca2+ on the parathyroid, we examined hyperplastic human parathyroid tissue for Ca2+ and calmodulin-dependent protein kinase activity. In parathyroid homogenates, Ca2+ stimulates the phosphorylation of substrate protein in the presence of calmodulin or phospholipid. The calmodulin (CaM)-stimulated activity is present in a soluble fraction of parathyroid and can be separated from other protein kinase activities by gel filtration chromatography. The concentration dependence of CaM kinase on Ca2+ and CaM was determined using the gel filtration. The Ka values for CaM and calcium were 100 nM and 5 microM, respectively. The fraction containing the CaM kinase activity had a calculated mol wt of 5.5 X 10(5). It contained a protein with a mol wt of 4.9 X 10(4) whose phosphorylation was Ca2+ CaM dependent and a CaM-binding protein of mol wt 4.9 X 10(4) which we suggest may be the catalytic subunit of a type II Ca2+-CaM dependent protein kinase. Hyperplastic human parathyroid tissue contains a type II Ca2+-CaM dependent protein kinase which may serve an important function in Ca2+-directed metabolism. PMID- 3096700 TI - Early short photoperiod effects in female LSH/SsLak Syrian hamsters. AB - Previous experiments showed that LSH/SsLak female hamsters cease ovarian cyclicity after 2-4 weeks of short photoperiod (SP) treatment. This study was designed to reveal early hormonal and histological changes on day 1 of the estrous cycle (estrus) in SP-treated animals and changes brought about by the SP induced acyclic condition. Groups of 8-10 animals were killed on day 1 after 0, 4, 8, 12, and 16 days of SP treatment; sera and pituitaries were saved for hormone determinations, and ovaries were prepared for histological analysis. Intraatrial cannulae were inserted into anovulatory animals, and blood samples were withdrawn on the first and second postoperative days; the animals were killed on the third postoperative day. PRL levels were significantly reduced in cycling animals after 16 days of SP exposure and diminished further in acyclic animals. Pituitary PRL did not change in cycling animals, although it was highly depressed in SP-treated acyclic animals. The estrous FSH surge, serum LH levels, and pituitary gonadotropin contents were not affected by SP in cycling animals; in anovulatory animals, pituitary gonadotropin contents were significantly increased, and daily afternoon gonadotropin surges were observed. Uterine weights were reduced in cycling animals and underwent a further reduction after cyclicity ceased. Ovarian analysis revealed that all cycling animals had the same number of recruited follicles, yet significantly fewer corpora lutea and an apparent increase in atretic antral follicles were observed after 16 days of SP exposure. These results suggest that SP-induced cessation of estrous cyclicity occurs abruptly. SP does not alter the secondary FSH surge, but might adversely affect maintenance of follicular growth and depress serum PRL levels. PMID- 3096701 TI - In vivo and in vitro examination of an autoregulatory mechanism for luteinizing hormone-releasing hormone. AB - Recent evidence has been presented that demonstrates the existence of ultrashort feedback circuits for a number of neuropeptides in the central nervous system. The present investigation was undertaken to examine the possible existence of an autoregulatory mechanism for LHRH. In the first experiment, long term ovariectomized rats bearing lateral ventricular and atrial cannulae received intracerebroventricular (icv) injections of saline or LHRH every hour from 1200 1500 h. Blood was collected at 10-min intervals from 1200-1500 h to assess the effects of icv LHRH on pulsatile LH and FSH release. After the 1500 h collection, LHRH was injected iv and blood was collected to determine the effects of icv LHRH on pituitary responsiveness to LHRH. Central injections of 0.1 pg and 1 ng LHRH, but not 10 pg LHRH, significantly suppressed mean LH levels, trough LH levels, and LH pulse frequency compared to those in saline-treated control rats. The amplitude of LH pulses was not significantly affected by any dose of LHRH. In contrast to LH, multiple icv injections of LHRH failed to alter pulsatile FSH release. Pituitary LH and FSH responses to iv LHRH injection were not suppressed by icv LHRH. In a second experiment, hourly icv injections of 1 ng LHRH into proestrous rats markedly suppressed preovulatory LH release only during the middle to latter phases of the surge. In a final study using an in vitro superfusion system, addition of a LHRH agonist to the superfusion medium at a concentration that does not cross-react in the LHRH RIA suppressed basal and K+ stimulated LHRH release from medial basal hypothalamic fragments, but not from median eminence explants. These results support the existence and operation of an autoregulatory mechanism for LHRH in the central nervous system which may participate in the control of episodic LHRH release in ovariectomized rats and preovulatory LHRH release in proestrous rats. Seemingly, ultrashort-loop negative feedback regulation of LHRH requires the presence of structures other than nerve terminals in the MBH (i.e. cell bodies). PMID- 3096702 TI - In vitro release of luteinizing hormone-releasing hormone from the hypothalamus of old male rats. AB - The present experiments tested the ability of the hypothalamus of old male rats to release LHRH in vitro. Mediobasal hypothalami (MBH) of 18-month-old and 6 month-old male rats were perfused for a total of 5 h and 5 min; the amounts of LHRH released, both in basal conditions and after stimulation with high extracellular K+ (110 mM, applied for 5 min every 30 min), were measured in the effluent. Our results show that the basal secretion of LHRH from the perfused MBH of young and old male rats is quantitatively similar. Moreover, the MBHs of young and old animals are capable of responding to the repeated administration of a K+ stimulus with repeated bursts of LHRH hypersecretion. From a quantitative point of view, the MBHs of old animals respond to the K+ stimulus in a fashion similar to that found in younger animals; even if the responses to K+ of the hypothalami of old animals appear to be somewhat lower than those of the hypothalami of younger animals, the differences recorded were not significant. LHRH content (as measured by RIA) of the MBH before the perfusion period was similar in young and old animals. At the end of the experiment, the content of LHRH of the perfused hypothalamus was not significantly different in the old and young groups. Serum and intrapituitary levels of LH and FSH were significantly lower in 18-month than in 6-month-old animals. These data suggest that the alterations of the function of the hypothalamic-pituitary-gonadal complex observed in aged male rats are not due to an intrinsic age-related defect of LHRH-synthesizing neurons. PMID- 3096703 TI - Effect of vitamin E deficiency on serum concentrations of follicle-stimulating hormone and testosterone during testicular maturation and degeneration. AB - Although vitamin E has been recognized as a requirement for normal testicular function for more than 50 yr, the functional role of this fat soluble vitamin in the maintenance of spermatogenesis has not been clarified. Vitamin E deficiency has a deleterious effect on germ cell proliferation and differentiation in the rat and a variety of other animal species. The potential effect of vitamin E on the sensitivity of the hypothalmo-hypophyseal-gonadal feedback system has not been previously evaluated. Therefore, serum testosterone concentrations, androgen function in maintaining seminal vesicle weight, and citrate synthesis, as well as the circulating amounts of FSH, were determined in rats fed semipurified diets with vitamin E, control, and without vitamin E, vitamin E-deficient. To assess dietary effects before, during, and after testicular degeneration, analyses were carried out on animals fed the diets starting at 3 weeks of age and continuing for 1 yr. The defect produced by vitamin E deficiency does not reflect impaired gonadotropin function. There are no effects of vitamin E deprivation on either serum levels of testosterone or on seminal vesicle weight and citrate content suggesting that the LH-testosterone feedback loop is not impaired. The feedback loop of FSH and inhibin also appears to be normal. Serum FSH concentrations are not elevated, although the testis is germ cell depleted. Comparison of the vitamin E-deficient model to other models of testicular degeneration suggests that the effect of vitamin E occurs directly or indirectly on the regulation of intratesticular factors which regulate specific steps of germ cell development. PMID- 3096704 TI - Mechanisms of action of gonadotropin releasing hormone on rat granulosa cells. AB - To elucidate the mechanisms of stimulatory actions of GnRH on rat granulosa cells (GC), we have compared the actions of a GnRH agonist with those of a tumor promoting phorbol ester, 12-0-tetradecanoylphorbol 13-acetate (TPA) and Ca+2 ionophore, A23187. GC were obtained from immature (28-29 days old) rats 48 h after injection of 20 IU PMSG. Following prelabeling with 3[H]arachidonic acid (AA), the cells were incubated with the test substances for 10 min and AA release determined. A GnRH agonist, [D-Ala6, des-Gly-NH2(10)] GnRH ethylamide (GnRHa; 10 ng/ml) increased AA release 175% compared to the control value. AA release in the presence of GnRHa was larger than that due to 1 microM A23187 or 40 nM TPA alone. A23187 or TPA increased GnRHa-stimulated AA release further. GC were incubated with the test substances for longer time periods, i.e., up to 5 h. GnRHa caused a 4-fold increase in prostaglandin (PG) synthase activity at 5 h. GnRHa increased PGE accumulation to the same extent as TPA, but only increased PG synthase activity about half as much. In combination with TPA, GnRHa had no influence on TPA-stimulated PG synthase activity, but increased PGE accumulation to levels comparable to those with A23187 plus TPA. GnRHa caused a 2.5 fold increase in progesterone (P) accumulation, which was the same as TPA. P accumulation in the presence of GnRHa was affected by neither A23187 nor TPA. These data indicate that the combination of TPA and A23187 can substitute for GnRH action on PGE and P accumulation in rat GC. PMID- 3096705 TI - Membrane association of soluble protein activators of rat liver adenylate cyclase. Evidence for distinctness from the guanine nucleotide-binding stimulating protein (Ns). AB - Sonication of a crude rat liver membrane preparation and centrifugation at 100,000 X g yielded a supernatant which activated basal and hormone-sensitive adenylate cyclases [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. The membrane origin of the stimulatory activity was confirmed by the use of lactate dehydrogenase as a marker for contamination by cytosol. The solubility of the activating factors was verified by their passage through 0.05 micron diameter pores of Millipore filters. The membrane-derived activators were nondialyzable and destroyed by heat and trypsin in the same manner as adenylate cyclase activators detectable in cytosol. Stimulation by factors from membranes and cytosol was not additive. The amount of the activators which could be freed from membranes by sonication was 12-15% of that contained in cytosol previously separated from the membranes. Soluble activators from the two sources had limited ability to restore adenylate cyclase activity to membranes from the cyclone of S49 mouse lymphoma cells which are deficient in the enzyme's guanine nucleotide binding stimulatory protein, Ns. Cytosol did not contain a substrate for ADP ribosylation by cholera toxin that corresponded electrophoretically to Ns. Furthermore, purified Ns did not affect adenylate cyclase activity in preparations stimulated by the soluble activators. These findings suggest that the activating factors found in cytosol may be released from membranes during tissue homogenization. Because these protein activators can be obtained from membranes without use of detergents and can neither substitute for nor be substituted for by Ns in functional assays, they are distinct from Ns. PMID- 3096706 TI - AE mice: an inbred mouse strain with interesting features for epilepsy research. AB - Spontaneous clonic-tonic seizures were occasionally observed in inbred AE mice of both sexes. Determination of seizure thresholds in this strain showed that both female and male AE mice had electroconvulsive thresholds that were markedly lower than those of other strains of mice, whereas susceptibility to seizures induced by pentylenetetrazol was not increased. The antiepileptic drug phenobarbital was much less effective in blocking electroconvulsions in AE mice than in other strains. Similarly, valproic acid was less effective in protecting against pentylenetetrazol-induced seizures. These differences in anticonvulsant efficacy could be explained only partly by differences in pharmacokinetics, thus indicating a lower responsiveness of AE mice to antiepileptic drugs. Determination of the GABA-synthesizing enzyme glutamic decarboxylase in different brain regions showed no significant difference between AE mice and normal NMRI mice except for a lower GAD activity in corpus striatum of male AE mice. The data indicate that AE mice may be an interesting new genetic model of epilepsy. PMID- 3096707 TI - Pharmacological response of systemically derived focal epileptic lesions. AB - Focal epileptic lesions were made in rats by systemic focal epileptogenesis. In this method, a focal lesion of the blood-brain barrier (BBB) is produced by focal alpha irradiation followed by repeated systemic injection of a convulsant drug that cannot cross the normal BBB, resulting in a chronic epileptic focus. Changes in the spike frequency of these foci in response to various drugs was recorded. The controls, saline and chlorpromazine, produced no change. Phenytoin, phenobarbital, chlordiazepoxide, and valproic acid produced the expected decrease in spike frequency. Pentobarbital and diazepam produced a paradoxical increase in spike frequency. PMID- 3096708 TI - Influence of mouse liver stored vitamin A on the induction of mutations (Ames tests) and SCE of bone marrow cells by aflatoxin B1, benzo(a)pyrene, or cyclophosphamide. AB - Male mice (C57BL/6J) at 2 weeks of age were divided into two groups and maintained on a vitamin A-deficient or vitamin A-(retinyl acetate) supplemented diet. After 8 weeks, the average liver vitamin A concentration of mice fed on vitamin A-deficient or -supplemented diet was 36 +/- 7 micrograms/g vs 287 +/- 22 micrograms/g, respectively. Uninduced liver S9 fractions were prepared from both groups of mice and used to activate (with cofactors) the precarcinogens aflatoxin B1 (AFB), cyclophosphamide (CPP), dimethylbenz(a)anthracene (DMBA), and benzo(a)pyrene (BP) in the Salmonella mutagenicity assay. S9 fraction prepared from both groups of mice failed to activate CPP to metabolites mutagenic in tester strains TA100 and TA1535 or to activate DMBA to metabolites mutagenic in TA100, but effectively activated AFB and BP to metabolites mutagenic in TA98. Comparison of activation activities of S9 prepared from liver of mice fed a high or low level of vitamin A was made with T98 treated with AFB or BP using three doses of S9 (50, 100, and 200 microliters/plate). S9 fractions from mice with a high liver vitamin A level were consistently less potent than S9 fractions from mice with a low liver vitamin A level in activating AFB to its mutagenic metabolites. This effect was not observed in BP-treated plates. Administration of AFB to groups of mice with a high liver vitamin A level induced significantly less SCE in bone marrow cells than did administration of AFB to mice with a low liver vitamin A level. This differential sensitivity was not observed when the two groups of mice were treated with either BP or CPP. The possible relationship between vitamin A levels in vivo and mutagenesis or carcinogenesis are discussed briefly. PMID- 3096710 TI - Differential carcinogenic effects of intraperitoneal initiation with 7,12 dimethylbenz(a)anthracene or urethane and topical promotion with 12-O tetradecanoylphorbol-13-acetate in skin and internal tissues of female SENCAR and BALB/c mice. AB - Groups of female SENCAR or BALB/c mice were initiated once intraperitoneally with 300 micrograms/mouse of 7,12-dimethylbenz(a)anthracene (DMBA) or 20 mg/mouse of urethane at 7 weeks of age. Beginning one week later, mice received topically applied acetone or 12-O-tetradecanoylphorbol-13-acetate (TPA), once weekly, at 2.5 micrograms/mouse for weeks 1 through 6 and 1.25 micrograms/mouse for weeks 7 through 52. The skin lesions were evaluated clinically. A complete necropsy was performed on all mice at week 52. SENCAR mice exposed to DMBA/TPA and urethane/TPA had more skin tumors than SENCAR mice exposed to DMBA or urethane alone and more than BALB/c mice in any treatment group. Of all skin carcinomas diagnosed histologically in DMBA/TPA-exposed mice, less than one-third had been identified clinically while the mice were alive. Most of the carcinomas arose within papillomas. BALB/c mice developed more vascular and uterine tumors than did SENCAR mice injected with DMBA and more lung and vascular tumors than did SENCAR mice injected with urethane. TPA exposure after treatment with either initiator had no significant effect on internal tumor development in either SENCAR or BALB/c mice. PMID- 3096709 TI - SENCAR mouse skin tumorigenesis model versus other strains and stocks of mice. AB - The SENCAR mouse stock was selectively bred for eight generations for sensitivity to skin tumor induction by the two-stage tumorigenesis protocol using 7,12 dimethylbenz(a)anthracene (DMBA) as the initiator and 12-O-tetradecanoylphorbol 13-acetate (TPA) as the promoter. The SENCAR mouse was derived by crossing Charles River CD-1 mice with skin-tumor-sensitive mice (STS). The SENCAR mice are much more sensitive to both DMBA tumor initiation and TPA tumor promotion than CD 1, BALB/c, and DBA/2 mice. An even greater difference in the sensitivity to two stage skin tumorigenesis is apparent between SENCAR and C57BL/6 mice when using DMBA-TPA treatment. However, the SENCAR and C57BL/6 mice have a similar tumor response to DMBA-benzoyl peroxide treatment, suggesting that TPA is not an effective promoter in C57BL/6 mice. The DBA/2 mice respond in a similar manner to the SENCAR mice when using N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-TPA treatment. The SENCAR mouse model provides a good dose-response relationship for many carcinogens used as tumor initiators and for many compounds used as tumor promoter. When compared to other stocks and strains of mice, the SENCAR mouse has one of the largest data bases for carcinogens and promoters. PMID- 3096711 TI - Changes in NADH-ubiquinone reductase (complex I) with autolysis in the rat heart as experimental model. AB - Complex I (NADH-ubiquinone reductase) is a complex system located in the inner mitochondrial membrane and has the ability to catalyse several different enzymatic reactions concerned in electron transport. It is known to be one of the first components of the respiratory chain to be damaged by ischemia. Our results, using autolysis in the rat heart as experimental model, indicate that the NADH dehydrogenase system was impaired relatively early during ischemia while transhydrogenation and NADPH dehydrogenation appeared to be relatively resistant. PMID- 3096712 TI - The major polypeptide of scrapie-associated fibrils (SAF) has the same size, charge distribution and N-terminal protein sequence as predicted for the normal brain protein (PrP). AB - Scrapie-associated fibrils (SAF) are unique structures characteristic of the group of unconventional slow infections which includes scrapie and Creutzfeldt Jakob disease. A major component of hamster fibrils has been described as a protease-resistant glycoprotein with an apparent mol. wt of 27,000-30,000 (PrP27 30). However, we report here that if fibrils are prepared by procedures designed to minimise proteolysis the PrP proteins co-purifying with hamster SAF have mol. wts of 33,000-35,000 (PrP33-35) and 26,000-29,000 (PrP26-29). We find a Lys-Lys Arg-Pro-Lys sequence at the amino terminus of these SAF proteins, that is absent from PrP27-30, and which has recently been predicted to be the N-terminal sequence of the native PrP protein of uninfected brain. The major SAF protein (PrP33-35) and its normal brain homologue are shown to have the same apparent mol. wt and ionic charge distribution by two-dimensional gel analysis, silver staining and immunoblotting. These results support our view that PrP33-35 and the normal brain PrP protein may have the same covalent structure, and that the PrP protein is recruited into these amyloid-like SAF or into association with a non protein component of SAF by an irreversible event initiated directly or indirectly by scrapie infection. PMID- 3096713 TI - On the molecular mechanism of gypsy-induced mutations at the yellow locus of Drosophila melanogaster. AB - We determined the nucleotide sequence of genomic DNA corresponding to the yellow gene. The limits of the transcribed region were deduced from sequence analysis of yellow larval and pupal cDNA clones. The yellow transcription unit is simple, composed of two exons which are processed identically in both developmental stages into a mRNA of 1990 bp. The predicted yellow protein has a mol. wt of 60,752 daltons and appears to be a secreted protein having a structural function and not an enzymatic role in pigmentation. We also characterized the spontaneous mutation y2 and a revertant of this allele to investigate the mutagenic effect of the gypsy element inserted into this locus. Our results show that this transposon is inserted at -700 bp and that the y2+ revertant resulted from excision of the gypsy element leaving behind a complete long terminal repeat (LTR). We conclude, therefore, that the gypsy element is neither inserted into a pupal specific intron or regulatory sequence supporting the hypothesis that mutagenesis is a result of transcriptional interference by the gypsy element on the yellow gene. PMID- 3096714 TI - Site-specific disruption of clathrin assembly produces novel structures. AB - Clathrin assembly in vitro produces a highly ordered polyhedral structure (basket). This resembles clathrin assembled in situ on coated pits and vesicles which form during receptor-mediated endocytosis. Sites on clathrin involved in assembly were identified by assembling clathrin in the presence of anti-clathrin monoclonal antibodies. Three of the antibodies, as IgG, prevented the assembly of normal baskets, and their Fab fragments induced formation of two types of novel clathrin structures. Antibody effects on assembly and competitive binding data indicate these antibodies bind to two sites, critical for clathrin interactions, located in the same region of the clathrin heavy chain. Analysis of novel structures formed, suggested that nucleation but not further assembly was occurring, implying an ordered sequence of clathrin interactions during assembly. PMID- 3096715 TI - Early O-glycosidic glycosylation of proglucagon in pancreatic islets: an unusual type of prohormonal modification. AB - Proglucagon from rat islets is identified as a glycoprotein by its binding to soybean lectin and by the biosynthetic incorporation of [14C]galactosamine. Glycosylation can be demonstrated for both forms of proglucagon, i.e. the primary translation product which is detectable as early as 30 s after incubation of isolated islets with radioactive amino acids (proglucagon a), and its conversion product of slightly higher electrophoretic mobility which is formed after 5-10 min of incubation (proglucagon b). This glycosylation is determined to be of the O-glycosidic type by the following criteria: rat proglucagon has previously been shown to lack an acceptor sequence for N-glycosidic linkage of sugars, the sugar bond in rat proglucagon is labile under mild alkaline conditions, glycosylated serine is demonstrated in proteolytic lysates of both the early and the late form of this prohormone. O-glycosidic linkage of sugars has not been reported for other prohormones. Its early formation and the apparent absence of N glycosidically bound sugars in proglucagon give evidence for an unusual type of protein glycosylation. PMID- 3096716 TI - VHDJH formation and DJH replacement during pre-B differentiation: non-random usage of gene segments. AB - The Abelson murine leukemia virus (A-MuLV) transformed cell line 300-19 was derived from the bone marrow of an adult NIH/Swiss outbred mouse. The original 300-19 clonal isolate carried DHH rearrangements of both JH alleles, a molecular genotype characteristic of early pre-B cells. During propagation in culture, the 300-19 line frequently generates secondary rearrangements of its JH alleles including rearrangements which append VH segments to the pre-existing DJH complexes to form complete VHDJH variable region genes and secondary D to JH rearrangements which replace the pre-existing DJH rearrangement by joining an upstream D to a downstream JH. The two types of secondary rearrangement events occur at approximately equal frequency. Approximately 30% of the VH to DJH joins lead to the production of mu heavy chains providing support for a regulated model of allelic exclusion. Like pre-B cell lines from other origins, the 300-19 line preferentially utilized VH gene segments from the more JH-proximal (3') families to form VHDJH rearrangements. However, the VH segments preferentially employed by 300-19 were from a different family than those previously demonstrated to be utilized by pre-B lines of BALB/c origin; we relate these different utilization patterns to differences in the organization of the more 3' VH families between the two strains. The initial DJH rearrangements of the 300-19 line employed more 3' (JH-proximal) D segments; however, the DJH replacements preferentially employed the most 5' D segment. We discuss this phenomenon in the context of a mechanism which may target recombinase to regions of the chromosome more 5' to the D locus (VH-containing regions) once an initial DJH complex is formed. PMID- 3096717 TI - Structural analysis of high- versus low-affinity interleukin-2 receptors by means of selective expression of distinct receptor classes. AB - Activated T cells express at least two distinct affinity classes of interleukin-2 (IL-2) receptors. The number of low-affinity receptors per cell is normally 10-30 times greater than that of the high-affinity receptors, and the difference in the dissociation constant between the two classes of receptors is in the order of 1,000-fold. In this report normal human T cells are used in a cellular system in which the number of low-affinity receptors can be manipulated. It is demonstrated that a cell population could be achieved with such low levels of low-affinity IL 2 receptors that almost half of the surface pool of anti-IL-2 receptor antibody (anti-Tac) binding sites represented high-affinity receptors. By using this cellular system it was possible to show that anti-Tac recognizes both receptor classes with similar affinity and that IL-2 inhibits Tac binding to both receptor classes in a competitive fashion. Tac antigens were purified from surface 125I labeled cells expressing high levels of high-affinity IL-2 receptors, but low levels of the low-affinity receptor class, and this preparation was compared with another pool of Tac antigens obtained from cells expressing the normal 10- to 20 fold excess of low-affinity IL-2 binding sites over high-affinity IL-2 receptors. Biochemical characterization by peptide mapping by limited proteolysis and two dimensional gel analysis revealed that these distinct preparations of Tac antigens were indistinguishable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096718 TI - The Drosophila virilis dopa decarboxylase gene is developmentally regulated when integrated into Drosophila melanogaster. AB - The dopa decarboxylase gene (Ddc) has been isolated from Drosophila virilis and introduced into the germ-line of Drosophila melanogaster by P-element mediated transformation. The integrated gene is induced at the correct stages during development with apparently normal tissue specificity, indicating that cis-acting elements required for regulation are functionally conserved between the two species. A comparison of the DNA sequences from the 5' flanking regions reveals a cluster of small (8-16 bp) conserved sequence elements within 150 bp upstream of the RNA startpoint, a region required for normal expression of the D. melanogaster Ddc gene. PMID- 3096720 TI - Survey of schistosomiasis mansoni in the Borkena river basin, Ethiopia. PMID- 3096719 TI - Production of specific antibodies against protein A fusion proteins. AB - The gene for Staphylococcal protein A was fused to the coding sequence of bacterial beta-galactosidase, alkaline phosphatase and human insulin-like growth factor I (IGF-I). The fusion proteins, expressed in bacteria, were purified by affinity chromatography on IgG-Sepharose and antibodies were raised in rabbits. All three fusion proteins elicited specific antibodies against both the inserted protein sequences and the protein A moiety. In the case of IGF-I, the protein A moiety in the fusion protein may act as an adjuvant since native IGF-I alone is a poor immunogen. The results suggest that the protein A fusion system can be used for efficient antibody production against peptides or proteins expressed from cloned or synthetic genes. To facilitate such gene fusions a set of optimized vectors have been constructed. PMID- 3096721 TI - Gastric secretion inhibited by disodic EDTA. PMID- 3096722 TI - Ventilation effects of nitrous oxide during continuous infusion of fentanyl or alfentanil. PMID- 3096723 TI - Intravenous anaesthesia for cystoscopy: a comparison of propofol or methohexitone with alfentanil. AB - Sixty out-patients undergoing cystoscopy were allocated randomly into two groups. No premedication was given. Induction of anaesthesia was preceded by intravenous alfentanil 7 micrograms kg-1 given over 20 s, followed by methohexitone 1.5-2 mg kg-1 or propofol 2 mg kg-1, given over 20 s. Anaesthesia was maintained by increments of alfentanil, methohexitone or propofol, given as required. PMID- 3096724 TI - Ventilatory changes during nitrous oxide isoflurane anaesthesia in children. AB - The changes in ventilatory variables under nitrous oxide isoflurane anaesthesia were studied in 10 children (mean age 46 +/- 13.4 months, mean weight 16.2 +/- 2.1 kg). Measurements of flow and volume were performed by pneumotachography. PE'CO2 was measured by capnography. The following variables (VE, VT, TI/TTOT, VI, PE'CO2) were measured or calculated under three increasing inspired isoflurane concentrations (0.75%, 1.5%, 2.25%). At each level of anaesthesia, ventilatory changes during exposure to an inspired CO2 fraction of 2% were studied. The increase in the inspired concentration of isoflurane was associated with a decrease in alveolar ventilation. PE'CO2 increased significantly with increasing depth of anaesthesia. The respiratory rate was slightly increased under light nitrous oxide isoflurane anaesthesia, but no further changes were observed with increasing depth of anaesthesia, although the children were breathing a mixture of nitrous oxide and oxygen. The ventilatory response to a raised inspired CO2 is markedly decreased under light nitrous oxide isoflurane anaesthesia, and decreases significantly with increasing depth of anaesthesia. In response to a raised CO2, VE, VT and VI increase, but respiratory rate decreases or remains constant and TI/TTOT is unchanged. PMID- 3096725 TI - Alterations in plasma-volume-corrected blood components of marathon runners and concomitant relationship to performance. AB - The study was undertaken to determine the effects of running a marathon on concentration of various blood components resulting from phenomena other than fluid loss, and these were related to performance times. Twenty male marathon runners ranging from 20 to 50 years of age participated in the study. Blood samples were collected before and after the subjects ran in a marathon. Blood samples were analyzed for sodium, potassium, glucose, lactate dehydrogenase, creatinine, creatine phosphokinase, triglycerides, cholesterol, hematocrit, hemoglobin, protein, white blood cell number, uric acid, carbon dioxide, and iron. All of the blood parameters increased significantly in concentration with the exceptions of glucose and carbon dioxide which decreased. After accounting for plasma-volume loss (COR), there remained significant increases in blood serum lactate dehydrogenase, creatinine, creatine phosphokinase, uric acid, iron, and whole-blood white blood cell number. Significant decreases in COR serum sodium, protein, glucose, and carbon dioxide were found. Lactate dehydrogenase and creatine phosphokinase concentration changes support the concept of acute damage to muscle tissue resulting from marathon running. No strong relationship between performance time and other measured variables was found. COR measures were more representative of marathon induced blood changes from physiological dynamics other than plasma volume change than presently reported findings. PMID- 3096726 TI - In vitro activity of the two new 4-quinolones A56619 and A56620 against Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum and Gardnerella vaginalis. AB - The in vitro activity of tetracycline, ciprofloxacin and two recently developed 1 aryl-fluoroquinolones, A56610 and A56620, was tested against 65 beta-lactamase negative and 35 beta-lactamase-positive Neisseria gonorrhoeae strains, 12 Chlamydia trachomatis, 50 Mycoplasma hominis, 28 Ureaplasma urealyticum and 50 Gardnerella vaginalis strains. In the case of Chlamydia trachomatis and Mycoplasma hominis both the MIC and the MBC were determined. The MIC90 of ciprofloxacin for Neisseria gonorrhoeae was 0.008 microgram/ml and of A56619 and A56620 less than or equal to 0.03 microgram/ml. No difference was observed between the activity against beta-lactamase-negative and beta-lactamase-positive strains. The MIC90 values of of ciprofloxacin and A56620 for Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum were identical, the values being 2 micrograms/ml, 1 micrograms/ml and 4 micrograms/ml respectively. The MIC90 of A56619 for Chlamydia trachomatis and Ureaplasma urealyticum was 0.5 micrograms/ml and 1 microgram/ml respectively. The MBC90 values of the three quinolones for Chlamydia trachomatis and Mycoplasma hominis were less than or equal to 2 micrograms/ml. The activity of the quinolones against Gardnerella vaginalis was rather low, the MIC90 being greater than or equal to 4 micrograms/ml. It is concluded that A56619 and A56620 might be useful for single dose therapy of gonococcal infections. PMID- 3096728 TI - Methylation in vivo of elongation factor EF-Tu at lysine-56 decreases the rate of tRNA-dependent GTP hydrolysis. AB - In this paper we show, that the in vivo methylation of the elongation factor Tu from Escherichia coli is correlated with the growth phase of the bacterium. Methylation occurs at one position only, i.e. Lys-56, and initially results in monomethylation during logarithmic growth. Upon entering the stationary phase of E. coli, monomethyllysine is gradually converted into dimethyllysine. We have undertaken an extensive comparison between the properties of the highly methylated EF-Tu and unmodified EF-Tu. No gross conformational differences, as measured by the rate of mild tryptic cleavage, were observed. The dissociation rates of the nucleotides GDP and GTP appear likewise to be unaffected by the methylation, just as is the stimulatory effect of the elongation factor Ts upon these rates. Whereas tRNA binding at the classical binding site of EF-Tu (site I) also appears not to be affected by the methylation of the protein, tRNA binding at site II is. Although the apparent affinity of tRNA for site II remains unaltered upon methylation of EF-Tu, the conformational effects of tRNA binding at this site become different. Both the GTPase activity of the protein and the reactivity of Cys-81 are significantly less stimulated by the tRNA when EF-Tu is methylated. A possible physiological implication of this phenomenon is discussed. PMID- 3096727 TI - Modulation of adherence of coagulase-negative staphylococci to Teflon catheters in vitro. AB - The mechanism of adherence of Staphylococcus epidermidis to commercially available catheters was studied in vitro in a quantitative assay employing 3H labelled bacteria. It was found that adherence to Teflon catheters was significantly related to the degree of hydrophobicity of the strains. When hydrophobic groups were removed from Staphylococcus epidermidis by pepsin treatment, adhesion was almost completely abolished. Preincubation of catheters in human serum also caused a 80-90% reduction of adherence. Preincubation of Staphylococcus epidermidis in serum similarly decreased adhesion. This effect of serum was mainly due to albumin, while IgG and fibronectin were less effective. Culture of Staphylococcus epidermidis in subinhibitory concentrations (0.5 MIC) of cephalothin, clindamycin and vancomycin resulted in a 30-80% reduction in adhesion. PMID- 3096730 TI - Covalent labelling of histones with aurothiomalate. Gold-labelled H2A-H2B dimers assemble to octamers, which form crystalline helical tubes. AB - Histone octamers were covalently labelled with aurothiomalate at amino groups by the method of carbodiimide activation. The labelling procedure was demonstrated to result in the specific covalent coupling through a single bond of the heavy metal atom label to protein amino groups. Such octamers were dissociated to yield soluble H2A-H2B dimers containing three gold atoms per dimer. The dimers were reconstituted with native H3-H4 tetramers to form labelled octamers, which were crystallized to form helical tubes. This strongly suggests that this procedure resulted in minimal changes of protein conformation. PMID- 3096729 TI - Protein synthesis in yeast Saccharomyces cerevisiae. Purification of Co-eIF-2A and 'mRNA-binding factor(s)' and studies of their roles in Met-tRNAf.40S.mRNA complex formation. AB - Antibodies prepared against a homogeneous preparation of Co-eIF-2A20 [Ahmad et al. (1985) J. Biol. Chem. 260, 6955-6959] reacted with several polypeptides including an 80-kDa polypeptide present in a crude yeast ribosomal salt wash. This 80-kDa polypeptide, containing Co-eIF-2A (Co-eIF-2A80) activity, has been extensively purified using a two-step purification procedure involving an immunoaffinity column chromatograph prepared using antibodies against Co-eIF-2A20 (fraction II) and hydroxyapatite chromatography (fraction III). The factors, eIF 2 + homogeneous Co-eIF-2A80 (fraction III) promoted Met-tRNAf.40S complex formation with an AUG codon but not with a physiological mRNA or a polyribonucleotide messenger poly(U,G) whereas eIF-2 + a partially purified Co eIF-2A80 preparation (fraction II) promoted Met-tRNAf.40S complex formation with an AUG codon as well as with globin mRNA and poly(U,G) messenger. This factor promoted Met-tRNAf binding to 40S ribosomes depends absolutely on the presence of a polyribonucleotide messenger containing an initiation codon (such as AUG or GUG). Other polyribonucleotide messengers tested, such as poly(U), poly(A) and poly(A,C) were completely ineffective in this binding reaction. This result indicates that the Met-tRNAf.40S.mRNA complex is formed by a direct interaction between Met-tRNAf, 40S ribosomes and the initiation site in mRNA. A mechanism has been proposed for Met-tRNAf.40S.mRNA complex formation in yeast. PMID- 3096731 TI - ADP-ribosylation of platelet actin by botulinum C2 toxin. AB - Botulinum C2 toxin is a microbial toxin which possesses ADP-ribosyltransferase activity. In human platelet cytosol a 43-kDa protein was ADP-ribosylated by botulinum C2 toxin. Labelling of the 43-kDa protein using [32P]NAD as substrate was reduced by unlabelled NAD and nicotinamide. The label was removed by treatment with snake venom phosphodiesterase. Half-maximal and maximal ADP ribosylation occurred at 0.1 microgram/ml and 3 micrograms/ml botulinum C2 toxin, respectively. The Km value of the ADP-ribosylation reaction for NAD was about 1 microM. The peptide map of the ADP-ribosylated 43-kDa protein was almost identical with platelet actin. The ADP-ribosylated 43-kDa substrate protein bound to and was eluted from immobilized DNase I in a manner similar to G-actin. Trypsin treatment of platelet cytosol decreased subsequent ADP-ribosylation of the 43-kDa protein without occurrence of smaller labelled polypeptides. Purified platelet actin was also ADP-ribosylated by botulinum C2 toxin with similar characteristics found with actin in platelet cytosol. Phalloidin decreased the ADP-ribosylation of actin in platelet cytosol and of isolated platelet actin. Half-maximal and maximal, about 90%, reduction of actin ADP-ribosylation was observed at 0.4 microM and 10 microM phalloidin, respectively. ADP-ribosylation of purified actin, induced by botulinum C2I toxin, abolished the formation of the typical microfilament network. The data indicate that platelet G-actin but not F actin is a substrate of botulinum C2 toxin and that this covalent modification largely affects the functional properties of actin. PMID- 3096732 TI - Biosynthesis of the wall neutral polysaccharide in Bacillus cereus AHU 1356. AB - The pathway for the biosynthesis of a cell wall polysaccharide, composed of glucosamine, mannosamine, galactosamine and glucose in a molar ratio of 4:1:1:1, was studied with a membrane system from Bacillus cereus AHU 1356. In this system a glycolipid characterized as GalNAc(alpha 1----4)ManNAc(beta 1----4)GlcNAc-PP undecaprenol was formed from GlcNAc-PP-undecaprenol by sequential transfer of N acetylmannosamine and N-acetylgalactosamine residues from UDP-ManNAc and UDP GalNAc respectively. An additional N-acetylglucosamine residue and a glucose residue were individually transferred from their UDP derivatives to the trisaccharide-linked lipid with the formation of tetrasaccharide-linked lipids, which seem to serve as intermediates in the polysaccharide synthesis. Incubation of membranes with the trisaccharide-linked lipid even in the absence of sugar linked nucleotides led to the formation of polysaccharide. These results, together with the data on Smith degradation of the synthesized polysaccharide, indicate that the repeating trisaccharide units of the main chain of the polysaccharide arise from the GalNAc-ManNAc-GlcNAc moiety of the glycolipid intermediates and that the sugar residues in the lateral branches of the polymer are at least partly introduced through oligosaccharide-linked lipid intermediates. In addition, the structure of native polysaccharide was re examined, and the presence of the disaccharide sequence ManNAc(beta 1----4)GlcNAc in the polysaccharide chain was confirmed. PMID- 3096733 TI - Reduced stability of RNA coding for yolk polypeptide 3 in Drosophila melanogaster ovary. AB - In Drosophila three yolk polypeptides (YP1, YP2 and YP3) are synthesized at two sites in the adult female: in the fat body tissue, from which they are transported via the haemolymph to the ovary, and in the ovarian follicle cells which surround the developing oocytes. All three yolk polypeptides are synthesized at equal levels in the fat body. In this paper we show that the steady-state level of YP3 RNA is significantly reduced in the ovary in comparison with the fat body, and that none of the yolk protein genes is amplified either in the fat body or the follicle cells. In order to determine the basis of the reduced level of YP3 RNA in the ovary, which could result from a lower rate of transcription or through a decreased stability of the RNA, we have devised an in vivo method of determining relative rates of gene transcription. In both the fat body and the ovary all three yolk proteins are transcribed at similar rates. Thus we infer that YP3 RNA is destabilised in the ovary, accounting for the reduction in its steady-state level. PMID- 3096734 TI - Purification and characterization of propylamine transferase from Sulfolobus solfataricus, an extreme thermophilic archaebacterium. AB - The enzyme propylamine transferase, catalyzing the transfer of the propylamine moiety from S-adenosyl(5')-3-methylthiopropylamine to several amine acceptors, has been purified 643-fold in 20% yield from Sulfolobus solfataricus, an extreme thermophilic archaebacterium optimally growing at 87 degrees C. The purified enzyme (specific activity 2.05 units/mg protein), is homogeneous by criteria of gel electrophoresis, gel filtration, isoelectric focusing and ultracentrifugation analysis. The molecular mass of the native enzyme was estimated to be about 110 kDa by gel permeation and ultracentrifugation analysis. The protein migrates on SDS/polyacrylamide gel electrophoresis as a single band of 35 kDa, suggesting that the enzyme is a trimer composed by identical subunits. An optimum pH of 7.5 and an acidic isoelectric point of 5.3 have been calculated. The optimum temperature was 90 degrees C and no loss of activity is observable even after exposure of the purified enzyme to 100 degrees C for 1 h. No reducing agents are required for enzymatic activity. Substrate specificity towards the amine acceptors is rather broad in that 1,3-diaminopropane (Km = 1675 microM), putrescine (Km = 3850 microM), sym-norspermidine (Km = 954 microM) and spermidine (Km = 1539 microM) are recognized as substrates. Conversely S-adenosyl(5')-3 methylthiopropylamine is the only propylamine donor (Km = 7.9 microM) and the deamination of the sulfonium compound prevents the recognition by the enzyme. The reaction is irreversible and initial-rate kinetic studies indicate that the propylamine transfer is operated through a sequential mechanism. 5' Methylthioadenosine, a product of the reaction, acts as a powerful competitive inhibitor with a Ki of 3.7 microM. Enzyme-substrate binding sites have been investigated with the aid of several substrate analogs and products. Among the compounds assayed, 5'-methylthiotubercidin, S-adenosyl(5')-3-thiopropylamine and S-adenosyl-3-thio-1,8-diaminooctane are the most active inhibitors. PMID- 3096735 TI - Structure and functions of linkage unit intermediates in the biosynthesis of ribitol teichoic acids in Staphylococcus aureus H and Bacillus subtilis W23. AB - The stepwise formation and characterization of linkage unit intermediates and their functions in ribitol teichoic acid biosynthesis were studied with membranes obtained from Staphylococcus aureus H and Bacillus subtilis W23. The formation of labeled polymer from CDP-[14C]ribitol and CDP-glycerol in each membrane system was markedly stimulated by the addition of N-acetylmannosaminyl(beta 1----4)N acetylglucosamine (ManNAc-GlcNAc) linked to pyrophosphorylyisoprenol. Whereas incubation of S. aureus membranes with CDP-glycerol and ManNAc-[14C]GlcNAc-PP prenol led to synthesis of (glycerol phosphate) 1-3-ManNAc-[14C]GlcNAc-PP-prenol, incubation of B. subtilis membranes with the same substrates yielded (glycerol phosphate)1-2-ManNAc-[14C]GlcNAc-PP-prenol. In S. aureus membranes, (glycerol phosphate)2-ManNAc-[14C]GlcNAc-PP-prenol as well as (glycerol phosphate)3-ManNAc [14C]GlcNAc-PP-prenol served as an acceptor for ribitol phosphate units, but (glycerol phosphate)-ManNAc-[14C]GlcNAc-PP-prenol did not. In B. subtilis W23 membranes, (glycerol phosphate)-ManNAc-[14C]GlcNAc-PP-prenol served as a better acceptor for ribitol phosphate units than (glycerol phosphate)2-ManNAc [14C]GlcNAc-PP-prenol. In this membrane system (ribitol phosphate)-(glycerol phosphate)-ManNAc-[14C]GlcNAc-PP-prenol was formed from ManNAc-[14C]GlcNAc-PP prenol, CDP-glycerol and CDP-ribitol. The results indicate that (glycerol phosphate)1-3-ManNAc-GlcNAc-PP-prenol and (glycerol phosphate)1-2-ManNac-GlcNAc PP-prenol are involved in the pathway for the synthesis of wall ribitol teichoic acids in S. aureus H and B. subtilis W23 respectively. PMID- 3096736 TI - In-111 Pseudomonas aeruginosa: a simple method of labeling live bacteria with a gamma-emitting radioisotope. AB - We describe a simple and reliable technique for labeling Pseudomonas aeruginosa with a readily available commercial preparation of indium-111 (111In) oxine. Labeling of a heavy bacterial suspension with 500 mu Ci of commercially prepared 111In-oxine resulted in a yield of 0.0004 mu Ci of cell-associated 111In per 10(6) colony-forming units (CFU). The label was 88% bacterially associated and did not effect viability of the organism. Radiolabeling a gram-negative organism with 111In-oxine provides a non-toxic, stable gamma-emitting bacterial tracer. PMID- 3096737 TI - Prognostic and electroclinical features of grand mal epilepsies. AB - We studied the electroclinical features and prognosis of 103 patients with tonic clonic seizures alone. Patients were classified into three groups according to seizure semiology and interictal EEG: primary grand mal, focal grand mal and indeterminate grand mal. Discriminant analysis showed that a number of other electroclinical features had no significant classificatory power. Patients have been followed for 2-10 years. At the last observation 40% of patients were free from tonic-clonic seizures and 23% had fewer than 1 seizure a year, without differences among the three groups. The appearance of 'minor' (absence or partial) seizures during follow-up occurred in 12 patients and did not change the prognosis of tonic-clonic seizures. At the end of follow-up, 96% of patients had a normal social adjustment. Grand mal epilepsies therefore appear to have a good prognosis. PMID- 3096738 TI - Apolipoproteins AI, AII and HDL phospholipids but not APO-B are risk indicators for occlusive cerebrovascular disease. AB - A variety of lipids, lipoprotein (Lp) lipids and APO-Lp were measured in 72 patients of both sexes suffering from cerebrovascular arteriopathy and compared with a control group matched for age and sex. The best discriminators by univariate analysis were serum concentrations of APO-AI, followed by APO-AII, high density lipoprotein phospholipids and HDL cholesterol (HDL-C). Low density lipoprotein cholesterol and serum APO-B values were lower in the patients than in the controls. With APO-AI only, patients and controls could be classified with 88 91% certainty. By combination of some of the variables which were selected by a stepwise discriminant analysis, several models were calculated resulting in 93 97% segregation of patients from controls. By multivariate analysis, APO-AI, APO AII, HDL-C, and triglycerides in combination with the blood pressure or the body weight index were independent variables (in a mathematical sense). By comparing the present data with published results of previous studies it is concluded that cerebral atherosclerosis differs from other forms of atherosclerosis by several major risk indicators. PMID- 3096739 TI - Purification of an antibody-like protein from the sea star Asterias rubens (L.). AB - Cells from sea star (Asterias rubens) axial organs stimulated with trinitrophenyl (TNP) or fluoresceinyl-haptened polyacrylamide beads and subsequently stimulated in vitro with the same antigen produced and released a specific antibody-like protein which induced lysis of haptened sheep erythrocytes in the presence of serum complement. The anti-TNP antibody-like protein isolated by ammonium sulfate precipitation, gel filtration and affinity chromatography exhibited a single precipiting peak after crossed immunoelectrophoresis against rabbit antiserum to partially purified culture supernatant. The anti-TNP antibody-like protein gave a specific affinity precipitate in crossed affino-electrophoresis using a p nitrobenzoyl-substituted gel. The analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis under both reducing and nonreducing conditions evidenced a unique 30-kDa polypeptide chain. According to gel filtration experiments, the molecular weight of the major component isolated by affinity chromatography was about four times higher. Therefore, the antibody-like molecule could be a tetrameric protein devoid of any disulfide bond. PMID- 3096740 TI - Idiotope-specific T cell clones that recognize syngeneic immunoglobulin fragments in the context of class II molecules. AB - We have established idiotope (Id)-specific T cell lines and clones derived from at least 4 different BALB/c mice immunized with the light chain (lambda 2(315] of the BALB/c myeloma protein M315 (alpha, lambda 2). Independently derived clones were indistinguishable in that they reacted to V lambda 2(315), one or more of the amino acids corresponding to somatically mutated codons 94, 95 and 96 of the third hypervariable region being essential for expression of the Id. While the Id was efficiently expressed on V lambda 2(315), Fv315 and lambda 2(315) fragments, about a 100-1000-fold higher molar concentration of Fab315 and M315 was needed to induce equivalent responses. Thus, Ig quaternary structure heavily influenced the availability of the Id for T cells. The V lambda 2(315)-specific T cells were Thy 1.2+, L3T4+, Ly-2.2- and I-Ed restricted. Some of the T cell clones produced interleukin 2 (IL2), IL3 and B cell growth and differentiation factors upon activation. In addition, T cells were cytotoxic in long-term assays for Ed beta Ek alpha-, but not Ek beta Ek alpha- transfected L cells in the presence of Id. The cytotoxic effect was the basis for an L cell growth inhibition assay for T cell activation that was at least 10-fold more sensitive than ordinary proliferation assays. PMID- 3096741 TI - Synthetic peptides and beta-chain gene rearrangements reveal a diversified T cell repertoire for a lambda light chain third hypervariable region. AB - Twelve L3T4+ Ly-2.2- subclones, derived from 4 independent BALB/c T cell lines, responded to a combination of the I-Ed molecule and a synthetic peptide corresponding to residues 91-108 of the lambda light chain from BALB/c myeloma protein M315 (alpha, lambda 2). Peptide analogues in which the mutated residues Arg95 or Asn96 were exchanged with the corresponding germ-line-encoded Ser95 or Thr96 had an abolished or greatly reduced capacity to stimulate T cell clones. However, responses of subclones to an analogue where the mutated Phe94 was substituted with the germ-line-encoded Tyr94 revealed three specificity patterns: 5 clones reacted only with the lambda 2(315) peptide, 6 clones responded equally well to both peptides and a single clone reacted better with the Tyr94 analogue. Analysis of the T cell receptor beta-chain gene rearrangements disclosed 7 distinct rearrangements, identical rearrangements only being found for subclones originating from the same line. At least 3 different V beta genes were used. Subclones with identical or nearly identical peptide specificity, major histocompatibility complex-restriction and alloreactivity could differ in their V beta or J beta gene segment utilization. PMID- 3096742 TI - Accessory molecules and T cell activation. I. Antigen receptor avidity differentially influences T cell sensitivity to inhibition by monoclonal antibodies to LFA-1 and L3T4. AB - A series of BALB/c-derived T hybridoma cells, capable of producing interleukin 2 (IL 2) in response to poly(Glu60, Ala30, Tyr10) (GAT) presented by syngeneic B lymphoma cells in the context of Ad restriction determinants, was used as a model system to evaluate the roles of LFA-1 and L3T4 accessory molecules in antigen specific T cell activation. Examination of the antigen requirement for optimal IL 2 responses revealed marked differences in the apparent avidity of these cells for GAT/Ad complexes. A relationship was observed between this parameter and the susceptibility of T hybridoma cells to inhibition by monoclonal antibodies directed at 5 distinct epitopes of LFA-1, and at A beta d allodeterminants. In contrast, L3T4a-specific monoclonal antibodies were found to block in a similar fashion the antigen-specific IL 2 responses of T hybridoma cells, regardless of the apparent avidity of their antigen receptors. It was also shown that both L3T4+ and L3T4- T hybridoma cells were capable of recognizing GAT plus Ad with high avidity. Thus, the quality of T cell antigen recognition appears to critically influence the involvement of LFA-1, and only to a marginal extent that of L3T4, in antigen-specific T cell activation. The implications of these findings are discussed in the context of recent data indicating that L3T4 may not only be an Ia-binding protein. PMID- 3096743 TI - An attempt to produce "pre-T" cell hybridomas and to identify their antigens. AB - With the aim of identifying some of the stages in the development of pre-T cells (cells of the T cell lineage before they enter the thymus), we have produced a large number of hybridomas by the fusion of BALB/c bone marrow cells, bone marrow cells from BALB/c-nu/nu mice, BALB/c fetal liver cells and BALB/c fetal thymocytes with the AKR thymoma BW5147. The hybridomas were selected for the expression of the Thy-1.2 antigen of the normal cell donor and for their ability to produce interleukin 2 (IL 2) upon co-culture with irradiated normal spleen cells. A set of these hybridomas is described in this communication. The hybridomas were then used to immunize rats and to generate monoclonal antibody producing B cell hybridomas. Most, if not all, of the immunizing hybridomas were derived from pre-T cells as evidenced by the fact that they produce IL 2, and express some of the T cell markers (the Thy-1.2, Ly-1, Ly-2 or L3T4 antigens). The monoclonal antibodies were tested on a panel of pre-T cell hybridomas and on normal cells obtained from spleen, lymph nodes, thymus and bone marrow. The testing was carried out by the microcytotoxicity assay and flow cytometric analysis. Three groups of antibodies could be distinguished. Some antibodies were broadly reactive, being positive with virtually all the clones in the pre-T cell panel and with a substantial fraction of normal lymphoid cells. The identity of the antigens detected by these antibodies remains unknown but they do not seem to correspond to any of the known cell surface markers. Other antibodies reacted only with some of the pre-T cell clones and did not react at all with normal lymphoid cells obtained from adult animals. Finally, other antibodies still reacted only with a minor subpopulation of thymocytes or of thymocytes and bone marrow cells, as well as some of the pre-T cell clones; they did not react with spleen and lymph node cells. These antibodies might be specific for cells in the prethymic phase of the T cell differentiation pathway. They should prove useful for the identification of pre-T cell markers and hence for the isolation of pre-T cells and their functional analysis. PMID- 3096744 TI - B cell dependence of the congeneic barrier towards idiotype-carrying cells. AB - Immune cells transferred into nonirradiated animals of the same genotype face a barrier which severely affects their capacity to function in the host. We studied this phenomenon in allotype-congeneic animals. When anti-dextran immune cells of the responder strain (BALB/c-Igha) are injected into an allotype-congeneic host (BALB-Ighb) the grafted cells are suppressed to give an idiotype-positive response. This congeneic barrier of thymus-independent immune cells is lost in mice carrying an X-linked B cell defect: when idiotype-positive immune cells from responder (CBA/N X BALB/c)F1 mice are transplanted into congeneic nonresponder animals (CBA/N X BALB-Ighb)F1, female recipients are nonpermissive towards grafted cells whereas B cell-defective male littermates allow donor cells to develop an idiotype-positive anti-dextran response. These results show that the congeneic barrier towards dextran-immune cells is related to the maturation stage of B cells in the recipient. Since B cell-defective (CBA/N X BALB/c)F1 animals do not display an anti-idiotypic response in contrast to intact littermates and because CB16-KN mice are nonpermissive towards CB8-K lymphocytes, differing in VH genes only, we suggest that the "isogeneic barrier" depends on a mechanism recognizing VH structures. PMID- 3096745 TI - Stable expression of Lyt-2 homodimers on L3T4+ T cell clones. AB - The murine T lymphocyte antigen Lyt-2 is considered to act as an accessory molecule to the class I-restricted T cell receptor during antigen recognition. We have previously described two unusual Lyt-2+L3T4+ class II-restricted T cell clones whose activation by antigen is inhibited by antibodies to L3T4 but not to Lyt-2 (B. Fazekas de St. Groth et al., Proc. Natl. Acad. Sci. USA 1986. 83: 2594). The Lyt-2 immunoprecipitated from one of these clones was indistinguishable from the molecule found on splenic T cells, as analyzed under reducing conditions on polyacrylamide gels, in two-dimensional charge/size separations and in peptide mapping. The molecule from the second clone showed slightly more extensive glycosylation but was within the range described for functional Lyt-2 on cytotoxic T cell lines. Lyt-2 mRNA from both clones showed no abnormalities on Northern analysis. Lyt-2 is normally expressed on thymocytes and peripheral T cells as a heterodimer disulfide bonded to the Lyt-3 glycopeptide, yet Lyt-3 could not be detected on the cell membranes of our clones; Lyt-2 existed as stable homodimers without Lyt-3. Thus Lyt-3 is not required structurally for the spontaneous expression of Lyt-2 on lymphoid cells. PMID- 3096746 TI - Induction of chronic idiotype suppression by ligands binding to the variable (not the constant) region of the idiotypic target. AB - It was previously shown that in C57BL/6 mice chronic suppression of an idiotypically defined subset of lambda 1 chain-bearing anti-(4-hydroxy-3 nitrophenyl)acetyl (NP) antibodies is achieved by neonatal administration of allogeneic monoclonal anti-idiotope antibodies reactive with this subset, or by NP coupled to mouse immunoglobulin. The present data show that isologous monoclonal anti-idiotope antibodies have the same effect. In contrast, antibodies against constant region determinants of lambda 1, mu or delta immunoglobulin chains failed to induce chronic suppression of the same antibody subset. Furthermore, the effect of the anti-idiotope antibodies was neutralized by idiotypic antibodies of the IgG1 class, injected before or together with the anti idiotype. These results suggest that the mere complexing of idiotypic molecules on the B cell surface or in the circulation is insufficient for the induction of chronic idiotype suppression. In the present system, induction appears to require the binding of a ligand to idiotype-bearing receptor V regions, expressed on the surface of B (or T?) cells. PMID- 3096747 TI - Phenotypic characterization of individual interferon-gamma-producing cells after OKT3 antibody activation. AB - This is the first study using a direct approach to determine the phenotype of interferon gamma (IFN-gamma)-producing cells after polyclonal T cell activation. Blood mononuclear cells (MNC) were cultured and stimulated by OKT3 antibody to produce IFN-gamma. They were then stained with a panel of monoclonal antibodies with specificity for cell surface antigens, fixed and permeabilized in suspension and stained for cytoplasmic IFN-gamma using monoclonal antibodies and indirect immunofluorescence technique. IFN-gamma appeared mainly as a local, polar accumulation in the cytoplasm in a juxtanuclear position, probably identical to the Golgi apparatus. After a culture period of 20 h, 6-11% and 0.2-0.6% of the OKT3-activated MNC from adults or newborns, respectively, produced IFN-gamma in cultures. Unstimulated cultures contained maximally 0.1% IFN-gamma-positive MNC. The majority of the IFN-gamma-producing MNC were T cells and expressed the T11 antigen and receptors for interleukin 2. To our surprise most of these T cells also carried receptors for complement 3bi (OKM1) but did not express class II molecules. Less than 50% displayed T4 or T8 antigens in three out of the four experiments performed. Natural killer cells, as recognized by Leu 7 or B73.1 antibodies, contributed only marginally to the IFN-gamma synthesis whereas B cells (OKB7) and monocytes (Leu M3) showed no production of IFN-gamma. PMID- 3096748 TI - Intracellular pathway of interleukin 2 following receptor-mediated endocytosis. AB - Electron microscope autoradiography was used to examine the intracellular pathway of radioiodinated interleukin 2 [( 125I]IL2) following its receptor-mediated endocytosis in CTLL cells. Direct measurement of the kinetics of endocytosis showed that 60-70% of surface-bound [125I]IL2 was internalized after 1 h at 37 degrees C. [125I]IL2 was observed to enter cells through invagination of coated pits at the cell surface and to concentrate into lysosomal multivesicular bodies as early as 5-10 min after endocytosis. These results provide ultrastructural information on the intracellular pathway of IL2 and on its probable site of degradation within the cell. PMID- 3096749 TI - Antipyretic analgesics inhibit prostaglandin release from astrocytes and macrophages similarly. AB - The effect of acid and non-acid antipyretic analgesics on prostaglandin (PG) release from cultured mouse astrocytes and peritoneal macrophages was investigated in order to test the hypothesis that the non-acid compounds are more potent inhibitors of PG formation in brain than in peripheral tissues. Stimulation of the cells by the divalent cation ionophore A 23187 (10(-6) mol/l) induced PG release from astrocytes and macrophages (mainly PGD2 and PGE2, respectively). This PG release was inhibited by acetylsalicylic acid (10(-5) - 10(-6) mol/l) and indomethacin (10(-6) - 10(-9) mol/l) but also by high concentrations (10(-3) - 10(-5) mol/l) of the non-acid compounds 4-methyl aminophenazone, the main active metabolite of dipyrone (metamizol), and acetaminophen (paracetamol). No difference was found in the inhibitory potency of the drugs in astrocytes and macrophages, suggesting that a specific sensitivity of brain cells toward non-acid antipyretic analgesics does not contribute to their analgesic effect. PMID- 3096750 TI - Uptake and metabolism of nucleosides by embryos of the sea urchin Strongylocentrotus purpuratus. AB - Uptake and metabolism of thymidine and adenosine have been studied in embryos of the sea urchin Strongylocentrotus purpuratus. Uptake of these nucleosides is found to be mutually competitive, with the Km for uptake of thymidine similar to its Ki for inhibition of adenosine uptake and vice versa. The metabolic studies show that adenosine is rapidly and completely phosphorylated upon entry, even at high exogenous concentrations which saturate the uptake mechanism. In contrast, at concentrations which saturate nucleoside uptake, thymidine becomes appreciably catabolized (up to 60%) to thymine and beta-amino-isobutyric acid in addition to its phosphorylation to thymine nucleotides. Negligible amounts of endogenous thymidine appear to remain unmetabolized following uptake in these embryos. The data provide strong in vivo evidence for separate metabolic pathways for thymidine and adenosine which have not previously been described in this organism. The observation of mutual competition during uptake, together with different routes of metabolism for these nucleosides, would suggest that the rate limiting step in the uptake process is transport rather than metabolism. The specificity of this transport system for its nucleoside substrate has been examined in some detail in the present report. All naturally occurring nucleosides but only a limited number of nucleoside analogs are recognized by this membrane carrier. Neither purine nor pyrimidine bases are substrates for this transport system. Previous work by this laboratory has demonstrated the strict Na+-dependence of this carrier, its high affinity for nucleoside substrate, and its activation at fertilization. These observations and the substrate specificity studies of the present work together describe a unique transport system for nucleosides in sea urchin embryos which is quite different from those previously described in mammalian cells. PMID- 3096751 TI - Concanavalin A binding induces association of possible mating-type receptors with the cytoskeleton in Tetrahymena. AB - The lectin concanavalin A (conA; 25 micrograms/ml) inhibits conjugation in the ciliate Tetrahymena, and binds to receptors localized at the junction between conjugating cells. We report here that succinyl-conA (30 micrograms/ml) has similar activity, but that two other mannosespecific lectins, lentil and pea lectins, have inhibitory activities more than tenfold lower in this system, indicating that factors other than mannose specificity are essential for biological activity. By using fluorescein-isothiocyanate (FITC)-conA, we have found that extraction of cells with the detergent Triton X-100 removes conA receptors from the extraction-resistant cytoskeleton, but that the binding of conA to its receptor before extraction associates the ligand-receptor complex with the cytoskeleton. Under the hypothesis that the conA receptor may be a mating type receptor, we have used this ligand-induced differential cytoskeletal association, in conjunction with electrophoresis and Western blotting, to identify a glycoprotein with an apparent molecular weight (MW) of 23,000 D which may be a mating type receptor. Our data are consistent with a model in which a direct interaction between the conA receptor and the cytoskeleton, rather than receptor cross-linking, is the biologically significant activity of ligand binding. PMID- 3096752 TI - Differentiation apparently repressed by the nucleus. Rapidly-induced pigmentation of enucleated melanoma cells. AB - There is evidence for cytoplasmic control over gene expression in cell differentiation, but still very little is known of the intracellular mechanism, nuclear, cytoplasmic, or both, which actively initiates the differentiation of one cell type into another. Here the role of the cytoplasm was examined in the induction of differentiation of cultured mouse melanoma cells by melanocyte stimulating hormone and alkaline medium. Intact cells were compared with cytoplasts, cells enucleated by centrifugation in the presence of cytochalasin D (CD). Surprisingly, early inductions of pigment (melanin) synthesis and of the principal melanin-synthesizing enzyme activity, tyrosinase, could be achieved in cytoplasts. Indeed these early changes were slower in nucleated cells and were accelerated by the inhibitor of protein synthesis, cycloheximide. Thus the initial activation of tyrosinase and melanin synthesis--although not necessarily any other or later aspects of melanoma cell differentiation--is apparently controlled through a labile, transcription- and translation-dependent repression. To our knowledge this is a novel mechanism for the initiation of differentiation; its generality remains to be tested. PMID- 3096754 TI - Gamma interferon and 1,25 dihydroxyvitamin D3 cooperate in the induction of monocytoid differentiation but not in the functional activation of the HL-60 promyelocytic leukemia cell line. AB - The physiological agents gamma interferon and 1,25 dihydroxyvitamin D3 (calcitriol) are both potent inducers of monocytoid differentiation in the HL-60 promyelocytic leukemia cell line. However, the populations resulting from treatment with either inducer have differing properties, suggesting that these agents do not have identical modes of action. In this study we have compared the effects of gamma interferon (IFN gamma) and calcitriol and examined the effect of exposing HL-60 cells to both compounds simultaneously. In addition, we have examined the effects of inhibitors of protein and RNA synthesis on induction of cell surface antigens in order to gain insight into the mechanisms of action of these compounds. We found that combining IFN gamma and calcitriol resulted in greater monocytic differentiation of HL-60 cells than did either compound alone. In addition, a monocyte-associated cell surface antigen, My23, and class-I HLA antigen were induced by both agents in at least an additive manner. In contrast, combined treatment with both compounds did not augment antibody-dependent cellular cytotoxicity (ADCC) any better than did IFN gamma alone, but it did cause a decrease in the density of receptors for the Fc portion of immunoglobulin. In studies examining the effects of IFN gamma and calcitriol on the cloning potential of HL-60 cells, we found that incubation of cells with either compound alone significantly reduced the number of HL-60 colonies, and both compounds added together caused an almost total elimination of colony forming cells. Inhibition of RNA synthesis with alpha amanitin had no effect on the action of IFN gamma on cell surface HLA, but did block the induction of My23 antigen, suggesting that the mechanism of HLA induction may involve posttranscriptional phenomena. RNA-synthesis blockade inhibited the ability of calcitriol to induce My23. These studies demonstrate that multiple and separable events accompany the monocytoid differentiation of HL-60 cells induced by different chemical mediators and that different intracellular pathways may be involved. PMID- 3096753 TI - Deoxyribonucleoside triphosphate metabolism and the mammalian cell cycle. Effects of hydroxyurea on mutant and wild-type mouse S49 T-lymphoma cells. AB - DNA precursor synthesis can be blocked specifically by the drug hydroxyurea (HU) which has therefore been used for anticancer therapy. High concentrations of HU, however, affect other processes than DNA synthesis; nevertheless, most studies on the biological action of HU have been made with concentrations at least one order of magnitude higher than those needed for cell-growth inhibition. In this study we characterized the effects of low concentrations of HU (i.e. concentrations leading to 50% inhibition of cell growth in 72 h) on cell cycle kinetics and nucleotide pools in mouse S49 cells with various defined alterations in DNA precursor synthesis. The effect of 50 microM HU on deoxyribonucleoside triphosphate pools was a 2-3-fold decrease in the dATP and dGTP pools, with no change in the dCTP pool and a certain increase in the dTTP pool. Addition of deoxycytidine or thymidine led to a partial reversal of the growth inhibition and cell-cycle perturbation caused by HU, and was accompanied by an increased level of the deoxyribonucleoside triphosphates. Addition of purine deoxyribonucleoside gave no protection, indicating that salvage of these nucleosides could not supply precursors for DNA synthesis in T-lymphoma cells. We observed a higher sensitivity to HU of cells lacking purine nucleoside phosphorylase or with a ribonucleotide reductase with altered allosteric regulation. Cells lacking thymidine kinase or deoxycytidine kinase were just as sensitive as wild-type cells. PMID- 3096755 TI - Antigenic analysis of hematopoiesis. VI. Flow cytometric characterization of My 10-positive progenitor cells in normal human bone marrow. AB - We have previously shown [1] that the anti-My-10 murine monoclonal antibody detected an epitope of a 115-kDa glycoprotein expressed specifically on KG-1a leukemia cells and a small subset of normal human bone marrow cells. This My-10+ marrow cell subset was shown to contain a highly enriched population of morphologic blast cells and hematopoietic colony-forming cells [1]. In this report, My-10+ cells were characterized, by flow cytometry, as an approximately 1% subpopulation of normal human bone marrow cells. My-10+ cells were slightly larger than lymphocytes and agranular, as determined by their fluorescence activating cell sorting (-er) (FACS) light-scattering properties. In two-color immunofluorescence experiments, My-10+ cells coexpressed the HLA-DR antigen. However, there was no detectable cellular coexpression of My-10 with either the Leu 1-5, 7, 9, 11, 15, M3, or My-18 antigens. There was an average of approximately 50,000 My-10 molecules per My-10+ marrow cell. This provides further evidence that the My-10 molecule is expressed, at relatively low levels, selectively on early human marrow cells but not on mature lymphohematopoietic cells. PMID- 3096756 TI - In vitro inhibition of hematopoiesis by HNK1, DR-positive T cells and monocytes after allogeneic bone marrow transplantation. AB - Blood CFU-GM and BFU-E, grown from 17 patients who had undergone allogeneic bone marrow transplantation (BMT), were studied by the plasma-clot technique before day 45, and at a time when their blood count was approximately normal. The number of colonies varied from one patient to another, but was always lower than in normal subjects. Removal of cells forming rosettes with sheep erythrocytes (E+C) increased colony growth in four out of eight cases, whereas removal of adherent cells (AC) had the same effect in five out of six cases. Addition of E+C or AC after their initial removal restored the inhibition of colony growth. This suppression was noted at a 1:1 to 8:1 cellular ratio and ranged from 25% to 75%. The phenotype of the suppressive cells was further characterized by complement mediated lysis with monoclonal antibodies (MoAbs) and fluorescent labeling. Two types of cells associated with inhibition of colony growth were identified: the first were E+C positive, characterized by the T3, HNK1, DR, and T8 determinants; the second were identified by the MO2 MoAb, indicating their monocytic origin, together with their properties of adherence. Similar suppressor cells of CFU-GM were found in the marrow of two other allogeneic BMT patients. A direct suppressive effect of the two types of cells was demonstrated in one experiment when MO2+ and/or HNK1+ cells collected by cell sorting were added back to cultures depleted in MO2+ and HNK1+ cells by complement-mediated lysis and were both found to decrease colony growth. Purified HNK1+ cells led to moderate inhibition of colony growth, which was not enhanced by increasing their concentration. This suppressive effect of hematopoiesis could be the consequence of an allogeneic reaction, since no inhibition was affected by T cells or monocytes in seven autologous BMTs and one syngeneic BMT. PMID- 3096757 TI - The relationship between immunodiffusion and agglutination serotypes of Mycobacterium avium and Mycobacterium intracellulare. AB - Twenty Mycobacterium avium/intracellulare strains of diverse origins and two reference strains of each of Schaefer's serotypes 1-21 were examined by immunodiffusion analysis. The results produced three distinct groups, which we have called A, B and C. Two of these, A and B, appear to be variants, perhaps subspecies of M. avium, and Group C is M. intracellulare. Within each group, rough variants, untypable by Schaefer's agglutination method, were found to be antigenically identical to the smooth parent strain by immunodiffusion analysis. The results obtained were essentially in agreement with those of some previous workers based on animal pathogenicity studies, skin-test studies in sensitized guinea-pigs and DNA homology. PMID- 3096758 TI - Compliance of COPD patients with long term oxygen therapy. PMID- 3096759 TI - Interindividual variability of the response to oxygen administration in hypercapnic patients. PMID- 3096760 TI - Effects of 2 and 4 l/min oxygen breathing on pulmonary artery pressure, blood gases and sleep stages in patients with chronic obstructive lung disease. PMID- 3096761 TI - Treatment of pulmonary hypertension with transdermal nitroglycerin. AB - Glycerol trinitrate in patches (DEPONIT 10) resulted in a statistically significant pressure drop in the pulmonary artery, the pulmonary capillaries, and the right atrium within 24 hours following drug application. This pressure reduction was recorded also after 4 weeks of continuous therapy. The reduction of pulmonary artery pressure and pulmonary vascular resistance is not only a consequence of improved pre- and afterload, but in addition also of a decrease in airways resistance and direct influence on arteriolar constriction in the pulmonary vascular bed. The beneficial effects upon pulmonary haemodynamics were equally recorded several months later. PMID- 3096762 TI - Pulmonary pharmacology: progress and controversy. PMID- 3096763 TI - Effects of almitrine bismesylate 100 mg daily for four weeks on respiratory regulation in patients with chronic bronchitis. AB - The effects on respiratory regulation of giving almitrine bismesylate (100 mg daily) orally for four weeks in twelve patients with chronic airflow obstruction were assessed in a double-blind placebo-controlled study. The drug caused significant increases in ventilation and the ventilatory response to hypoxia, associated with partial relief of arterial hypoxaemia and a fall in arterial CO2 tension. No consistent changes occurred with placebo. The results are in accord with a sustained action of almitrine bismesylates sensitising peripheral chemoreception. PMID- 3096764 TI - Effects of almitrine bismesylate on nocturnal hypoxemia in patients with chronic bronchitis and obesity. AB - In a double-blind placebo controlled randomised study, the effects of almitrine bismesylate on the sleep induced Hb desaturations, associated or not with disorders of breathing, were tested. Patients (37-75 yrs, 8M and 2F) were affected by chronic bronchitis (out of any exacerbation) and obesity (weight excess at least 20%). They were known to have at least one nocturnal episode of hypoxemia (SaO2 fall higher or equal to 10%) with respect to the wakefulness level. Patients received either placebo or almitrine (1.5 mg/Kg/day) for 18 days and nocturnal polysomnography was performed both before and the last day of treatment. Almitrine induced an increase in PaO2 during wakefulness (p less than .05), an increase in mean SaO2 during sleep (p less than .01) and a decrease in the quantity of desaturation (Qd) during sleep, defined as the product of the mean desaturation by the duration of the episodes of desaturation (p less than .025). No clear effect could be observed either on the mean duration of the sleep disordered breathing (SDB) events or on their frequency whereas the desaturations due to them had a decrease. PMID- 3096765 TI - The effects of almitrine at rest and on exercise in COPD patients. AB - Almitrine has significantly improved blood gases in patients with COPD without changing the pulmonary function either at rest or on exercise. Proceeding from these preliminary results we are about to start a long term study in our country. In the course of this we hope to clear up various problems, first of all the distinction between responders and non-responders should be made in order to clarify the indications for almitrine. If it would be possible to prove this effect in long term therapy, the benefits for the patients must be the same as for long term oxygen therapy. PMID- 3096766 TI - The assessment of almitrine bismesylate in the long-term treatment of chronic obstructive bronchitis. PMID- 3096767 TI - Long term studies on almitrine bismesylate in COPD patients. AB - Almitrine bismesylate is a chemoreceptor agonist which has been shown to improve arterial blood gas values in chronic obstructive pulmonary disease (COPD) patients, possibly through better ventilation/perfusion matching. On these basis, long term studies were undertaken to evaluate the therapeutic activity of almitrine bismesylate in COPD. We report here the overall results of 4 studies: a 6 months double blind placebo controlled study on clinical and biochemical data in 200 patients. a 12 months double blind placebo controlled study on clinical and hemodynamic data in 15 patients. a 12 months open study on clinical and biochemical data in 108 patients. a 52 months follow-up including therapeutic gap in 8 patients. Almitrine bismesylate group showed significant improvement of PaO2 and PaCO2 levels as compared with placebo group; this was found after 6 months of treatment and persisted after 12 months of treatment. 75% of almitrine treated patients were considered as responders, i.e. improved PaO2 and PaCO2 levels by at least 5 mmHg (0.665 KPa). Almitrine bismesylate groups showed significantly decreased dyspnea scores, received significantly less hospital care for acute decompensation or pulmonary infection and showed no significant change in hemodynamic parameters. After 20 months treatment interruption, patients showed progressively impairmed blood gas levels. Almitrine bismesylate ws well tolerated; nausea was occasionally observed and usually disappeared. Paresthesia was observed in some patients with identified predisposition. Altogether, these studies showed long term efficacy and acceptability of almitrine bismesylate in COPD patients with chronic respiratory failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096768 TI - Early auditory evoked potential changes during hypoxic hypoxia in the rabbit. AB - Early auditory evoked potentials and electroencephalograms were recorded in 10 rabbits during hypoxic hypoxia (5% O2 in N2 gas mixture) and after reoxygenation. In all experiments EEG flattening preceded the disappearance of the early evoked potential, whose recovery after reoxygenation was more rapid than that of the EEG. Significant increases in P3-P4 and P1-P3 interpeak latencies were observed during hypoxic conditions before the complete flattening of the early auditory evoked potential. In addition, negative relationships were found between the P3 P4 interpeak latency increase and mean arterial pressure reduction, and between the former and metabolic acidosis. PMID- 3096769 TI - Stimulation of synapsin I phosphorylation in synaptosomes by convulsants. AB - Pentylenetetrazole markedly enhanced synapsin I (previously referred to as protein I) phosphorylation and synaptosomal uptake of Ca2+. Picrotoxin and strychnine sulfate caused a slight increase in the phosphorylation and no significant increase in Ca2+ uptake. The data indicate that pentylenetetrazole appears to influence this process. PMID- 3096770 TI - Schistosoma mansoni: control of extramedullar eosinophil myelopoiesis in chronically infected mice by inflammatory macrophages. AB - Extramedullar proliferation of eosinophil granulocytes can be induced in mice chronically infected with Schistosoma mansoni, by intraperitoneal implants of glass coverslips. Immature eosinophils are located in discrete foci on glass implants; they are not correlated with the eosinophil population of the peritoneal cavity, where only mature eosinophils can be observed. The same induction of eosinophil proliferation can be obtained in normal mice, by the transfer of macrophages elicited by glass implants in mice with chronic schistosomiasis. This induction could not be done with cells mobilized in normal mice, either after transplant into normal mice or into schistosome infected ones. Stimulated macrophages of mice with chronic schistosomiasis have a capacity to induce peripherical proliferation of eosinophil granulocytes. This capacity is independent of the quality of the intraperitoneal environment. It can be expressed after transferring macrophages elicited in schistosome infected mice into normal mice. PMID- 3096771 TI - Schistosoma mansoni: activation of hemolytic activity in homogenates from live adult worms. AB - We have previously described hemolytic activity in extracts of lyophilized Schistosoma mansoni adult worms. In contrast, freshly homogenized live worms have little hemolytic activity. However, preincubation of the homogenate at 38 C, pH 5.1 for 22 hr resulted in an 18 fold increase in specific activity (Hb released/mg protein) due to dramatic increases in hemolytic activity and decreases in protein concentration. No activation occurred when the homogenate was boiled prior to preincubation or when preincubation was performed at 4 C. In addition, a thermostable inhibitor of hemolytic activity is present in freshly homogenized live adult S. mansoni. Hydrolysis of the inhibitor and activation of the hemolytic agent appear to be due in part to hydrolytic activity of one or more cysteinyl proteinases. PMID- 3096772 TI - Trypanosoma cruzi: protective immunization of susceptible strains of mice prone to autoimmunity. PMID- 3096773 TI - Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. I. Morphometric assessment of lymph node immunoreactivity and analysis of circulating antibodies. AB - To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mastocytoma grown in syngeneic DBA/2 mice, an approach was made to correlate immunomorphology of the lymph nodes with the functional assays measuring cytotoxic and tumor cell membrane-bound antibodies in mouse sera. Regional and non-regional (RLN, NRLN) lymph nodes, were subjected to stereological analysis to determine the volume fractions (Vv) of the cortex (C), the paracortex (PCA), the germinal centers (GC), and the medulla (M), using a computerized analysis system (IBAS I, Kontron). In both RLN:s and NRLN:s, lymphocyte subsets were identified and their ratios determined using the ABC (avidin-biotin peroxidase complex) technique and following monoclonal antibodies; Anti-Thy 1.2, Anti-Lyt 1, Anti-Lyt 2, and Anti-I-Ad. The 51Cr release assay was used to test the mouse sera for cytotoxic antibodies, and an indirect immunofluorescence (IF) technique to assess the sera for tumor cell membrane bound antibodies. There was a marked enlargement of the RLN:s reaching the peak on day 12, due to increase of the Vv of the B-zone as well as of the T-zone. Evidence of distinct B-cell stimulation by the growing of P815X2 was provided by an early decrease of Thy1.2+/I-Ad+ cell ratio both in the RLN:s and in NRLN:s. This activation of B-cells seems to be parallel to the elevation of Lyt1+/Lyt2+ ratio in T-cell region on day 6. The IF-tests for or the presence of tumor cell membrane-bound antibodies were almost invariably negative. With exception of two sera, the 51Cr-release assay for cytotoxic antibodies against P815X2 targets was negative. The present study confirms the previous observations on failure to find circulating cytotoxic or cell membrane-bound antibodies in DBA/2 mice bearing P815X2 mastocytoma, despite the morphologically well definable activation in RLN:s and in NRLN:s of the B-cell areas. This is in alignment with the findings in the majority of human tumors, where B-cell predominance in RLN:s does not represent a favourable prognostic sign. PMID- 3096774 TI - Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. II. Morphometric assessment of immunoreactivity in the thymus and spleen related to lymphocyte subsets in peripheral blood. AB - To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mastocytoma grown in syngeneic DBA/2 mice, an approach was made to correlate immunomorphology of the thymus and spleen with the functional assays measuring cytotoxic (51Cr-release assay) and tumor cell membrane-bound antibodies (IF test) as well as phenotyping (with monoclonal antibodies Anti Thy1.2, Anti-Lyt1, Anti-Lyt2, and Anti-I-Ad) the lymphocyte subsets in peripheral blood. The volume fractions (Vv) of the cortex (C), and medulla (M) of the thymus, as well as central (C-PALS) and peripheral periarteriolar lymphoid sheath (P-PALS) in the spleen were determined morphometrically. There was a steady increase of the C/M ratio from the control levels until day 8, not accompanied by any major fluctuations in the percentages of Thy1.2+ or I-Ad+ cells in C and M. In M, two significant peaks were found in Lyt1+/Lyt2+ cell ratio. In the spleen P PALS, Thy1.2+/I-Ad+ cell ratio was subject to major early elevation, followed by a rapid and permanent decline to levels below the controls. Two high peaks of Lyt1+/Lyt2+ ratio were found in P-PALS, on day 10 and 16. In the C-PALS, a marked decline in Thy1.2+/I-Ad+ ratio was observed throughout the experiment. As determined by Vv, there was a marked early enlargement of P-PALS reaching the peak on day 4, and followed by a steady reduction reaching the control values on day 10. In peripheral blood, there was an initial increase of T-cells, leading to elevated Thy1.2+/I-Ad+ ratio and a subsequent elevation of Lyt1+/Lyt2+ ratio on day 8.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096775 TI - Dopamine in the visual cortex of the cat. AB - The endogenous content of noradrenaline (NA) and dopamine (DA) was determined by radioenzymatic assays in three different areas of the occipital (visual) cortex, in normal cats as well as in DA-deafferented animals. The use of HPLC methodology enabled us to detect and measure in addition two metabolites of DA: 3, 4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), thus confirming the existence of a DA innervation in this cortical region. PMID- 3096776 TI - Extraneuronal serotonin accumulation in peripheral arteries of the rat. AB - Accumulations of serotonin (5-HT) and norepinephrine (NE) were compared in control and 6-hydroxydopamine (6-OHDA) pretreated rat aorta, mesenteric and tail arteries. The distribution of these amines was corrected by subtracting tissue uptake of tritiated sorbitol in the extracellular space. 5-HT greatly accumulated both in control and 6-OHDA pretreated arteries. In contrast, NE accumulation in mesenteric and tail arteries was substantially decreased after 6-OHDA treatment. In the aorta 6-OHDA pretreatment did not affect the accumulation of both amines. These findings suggest that 5-HT accumulation in these arteries is mainly extraneuronal, and NE mainly neuronal. Since the accumulation of 5-HT in the aorta was not influenced by pretreatment with 10 microM NE, the extraneuronal uptake mechanisms for 5-HT and NE appear to be different. PMID- 3096777 TI - Formation of lipoxin B by the pure reticulocyte lipoxygenase. AB - The pure reticulocyte lipoxygenase converts 5,15-DiHETE via a lipoxygenase reaction to 5,14,15-trihydroxy-6,8,10,12-eicosatetraenoic acid (a lipoxin B isomer) as shown by GC/MS analysis of its trimethylsilyl ether. With arachidonic acid, 15-HETE and 15-HETE methyl ester this lipoxin B isomer was also formed. The results presented here indicate that pure mammalian lipoxygenases are able to form lipoxins via sequential multiple oxygenation of arachidonic acid or its hydroxy derivatives. PMID- 3096778 TI - Purification of epidermal plasminogen activator inhibitor. AB - A plasminogen activator inhibitor was purified from human cornified cell extract by DEAE-Sepharose, Sephacryl S-200, and high-performance liquid chromatographies on hydroxyapatite HPHT and anion-exchanger Mono Q at pH 7.2 and 8.0. The purified inhibitor showed Mr 43,000 and pI 5.2 50% inhibition of fibrinolytic activity (1.5 IU) of urokinase and tissue-type plasminogen activator was attained by 0.60 ng and 11.0 ng purified inhibitor, respectively. Synthetic substrate assay demonstrated slow tight-binding inhibition to both urokinase and tissue-type plasminogen activator. The inhibitor did not inactivate plasmin, thrombin, glandular kallikrein or trypsin. PMID- 3096779 TI - Type 1 M protein of Streptococcus pyogenes. N-terminal sequence and peptic fragments. AB - Limited proteolysis of the surface of type 1 Streptococcus pyogenes by pepsin gives rise to fragment Pep M1 of Mr 20270 as the main product which covers the N terminal part of the M protein. The amino acid sequence was determined of the N terminal region of the M protein representing the most exposed part of the molecule on the surface fibrils of streptococcal cells, which seems to be very important for the differentiation of the individual serological types. The sequence differs from the homologous N-terminal sequences of types 5, 6 and 24, and shows a homology with sequences repeating in the chain of type 24. Fragment Pep M1 binds to fibrinogen; the absence of its 30 N-terminal amino acid residues, however, abolishes this interaction which is believed to play a role in the virulence of S. pyogenes. PMID- 3096780 TI - Mild endometriosis and ovulatory dysfunction: effect of danazol treatment on success of ovulation induction. AB - The effectiveness of ovulation induction with clomiphene citrate or human menopausal gonadotropins was evaluated in 52 infertile women with stage I or stage II endometriosis and ovulatory dysfunction: anovulation or luteinized unruptured follicle (LUF) syndrome before (group I) and after (group II) danazol treatment. The incidence of anovulation and LUF in the endometriosis population was 9% and 34%, respectively. In group I, 10 of 36 patients (27.8%) conceived, with an average of 17.6 induction cycles per pregnancy. In group II, 21 of 30 patients (70%) conceived, with an average of 4.5 cycles per pregnancy (difference significant at P less than 0.001). There was no difference in the average number of ovulation induction cycles per patient between groups I and II (4.9 and 3.1, respectively). Of 14 patients who did not conceive in group I and crossed over to group II, 9 (64.3%) conceived (not different from group II). Spontaneous abortion rates were 20% in group I and 14% in group II. These results indicate that mild endometriosis may interfere with conception through mechanisms other than ovulatory dysfunction and that treatment with danazol appears to more than double the fertility rate. PMID- 3096781 TI - Ultrasound-controlled gonadotropin therapy of anovulatory infertility. AB - Real-time ultrasound scanning of follicular development was performed during 45 cycles of 15 patients receiving gonadotropin therapy for treatment of anovulatory infertility. The amount of gonadotropins administered was based exclusively on the results of the ultrasound examinations. Fourteen pregnancies were obtained, with 10 singletons, 2 sets of twins, and 1 set of triplets, resulting in a cumulative pregnancy rate of greater than 93%. Mild hyperstimulation occurred in two cases. Ultrasound alone can be used effectively to control gonadotropin therapy in the majority of cases. PMID- 3096782 TI - Prolonged dopamine receptor blockade in normoprolactinemic amenorrhea: a double blind placebo study. AB - Patients with functional amenorrhea may have a raised central dopaminergic activity, leading to inhibition of pituitary-ovarian function. In a double-blind placebo trial, ten patients with amenorrhea received metoclopramide (MTC) orally in daily doses from 20 to 7.5 mg in a sequential form for 10 weeks. Six patients received placebo. Serum levels for luteinizing hormone (P less than 0.02), follicle-stimulating hormone (P less than 0.05), and prolactin (P less than 0.001) increased significantly during MTC administration, and no (P greater than 0.05) hormonal changes occurred in the placebo group. Six patients observed vaginal bleedings during MTC administration but without postovulatory progesterone levels. Dopamine receptor blockade may activate the hypothalamic pituitary axis of amenorrheic patients, although an ovulatory response is not achieved. PMID- 3096783 TI - Thyrotropin-releasing hormone and gonadotropin-releasing hormone test to predict effectiveness of bromocriptine therapy in infertile women. AB - Sixty-four infertile women presenting with luteal phase defect, anovulatory cycle, and secondary amenorrhea were compared with 15 normal cycling women with bolus injections of thyrotropin-releasing hormone (TRH) and gonadotropin releasing hormone (GnRH) before bromocriptine (BCPT) therapy. All of the women had normal baseline prolactin (PRL), luteinizing hormone (LH), and follicle stimulating hormone (FSH) concentrations. Responses of PRL, LH, and FSH levels were measured. PRL responses in BCPT responders were markedly greater than in controls and nonresponders. A better responder rate to BCPT therapy was observed in patients with apparent (88.9%) or borderline (69.2%) exaggerated responses of PRL to TRH than in normal patients (41.7%). Further, in patients with normal PRL responses, the inappropriately enhanced LH responses were seen in BCPT responders but not in nonresponders. These findings suggest that TRH and GnRH tests are worthwhile in predicting the outcome of BCPT therapy in infertile patients. PMID- 3096784 TI - Endocrinologic features of oligomenorrheic adolescent girls. AB - The plasma concentrations of sex hormones were measured in 45 oligomenorrheic and 28 regularly menstruating adolescent girls. Testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex hormone binding globulin levels were determined in blood samples collected during one menstrual cycle. The oligomenorrheic girls had significantly higher concentrations of luteinizing hormone, androstenedione, dehydroepiandrosterone sulfate, and free testosterone than regularly menstruating girls. Sex hormone binding globulin concentrations were significantly lower in the oligomenorrheic group. The oligomenorrheic girls were not obese. Signs of acne or hirsutism were absent or mild. Sixty-six percent of the oligomenorrheic cycles were ovulatory. The significance of the hormonal findings is discussed. PMID- 3096785 TI - Further demonstration of induction of ovulation with a hybrid human chorionic gonadotropin compound (AB1ER-CR-2XY). AB - Further demonstration of the ability of the hybrid human chorionic gonadotropin (hCG) compound, AB1ER-CR-2XY, to induce ovulation is presented. Nineteen patients previously treated with human menopausal gonadotropin (hMG) and commercial hCG were selected for the study. The patients received 37 courses of treatment with dosages of hMG ranging from 1200 IU (16 ampules) to 8400 IU (112 ampules), followed by the administration of 5000 or 10,000 IU of the hybrid hCG. Of the total number of courses given, 75.5% were ovulatory; serum progesterone levels at midluteal phase of the cycle were within normal range, and the cycle length was about 12 days. Seven patients became pregnant, three with twins, one with triplets, and three with aborted single fetuses. Before the hybrid hCG was administered the serum estrogen levels were less than 1200 pg/ml in 12 cycles (32.4%), and the estrogen levels ranged from 1400 to 7400 pg/ml in 25 (67.6%). However, in spite of high estrogen levels, clinical hyperstimulation, which occurred in 22.4% of previous treatments with conventional hMG-commercial hCG, did not develop when the hybrid hCG was administered, an effect which could be attributed to its short circulatory half-life. Studies are in progress to confirm whether the hybrid hCG may provide a better margin of safety than commercial hCG for ovulation induction in patients pretreated with hMG. PMID- 3096786 TI - Serum progesterone levels in women treated with human menopausal gonadotropin and human chorionic gonadotropin for in vitro fertilization. AB - For evaluation of the adequacy of luteal function after in vitro fertilization embryo transfer (IVF-ET), serum progesterone (P) levels were measured on days 3, 7, and 10 after laparoscopic follicle aspiration. Fifty-six infertile patients were treated during 86 cycles with human menopausal gonadotropin-human chorionic gonadotropin (hMG-hCG) for stimulation of follicular development. Serum estradiol (E2) levels were measured daily during hMG-hCG treatment. P levels were determined in 67 cycles. The mean (+/- standard deviation [SD]) of the sums of 3 P levels was 55.63 +/- 24.13 ng/ml. There were 11 pregnancies. The mean of the sums of 3 P levels of pregnant patients was 64.45 +/- 26.23 ng/ml and of 56 nonpregnant cycles was 53.90 +/- 23.35 ng/ml. The duration of luteal phase varied from 9 days to 15 days. The mean of the sums of 3 P values of patients with different luteal phase lengths ranged from 28.8 ng/ml to 60.51 +/- 25.68 ng/ml. The mean of the sums of 3 P levels of women with normal luteal phase and that of women with luteal phase defect by endometrial biopsy study were used as controls for comparison. There was poor correlation (r = 0.3441) between E2 peak levels and P levels; the sum of 3 P levels did not indicate luteal phase inadequacy in IVF-ET patients; and the majority of the nonpregnant cycles (32/56) showed a luteal phase of 11 days or less, in spite of adequate P levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096787 TI - Comparison of gonadal function between fertile and infertile men with varicoceles. AB - The high prevalence of men with varicoceles who by history are fertile has led some to question the suggested causal relationship between a varicocele and male infertility. However, testicular function in these fertile men has not previously been studied in detail. Fifty-five normal fertile men, 42 fertile men with varicoceles, and 24 infertile men with varicoceles and normal female partners were studied. Semen analyses were done, baseline serum testosterone and gonadotropin levels tested and the gonadotropin response to luteinizing hormone releasing hormone (LH-RH) measured. The infertile men with varicoceles exhibited lower sperm counts, abnormal sperm morphologic features, increased baseline serum gonadotropins, and increased gonadotropin responses to LH-RH, compared with the normal fertile men. The fertile men with varicoceles showed similar abnormalities, although this was not statistically significant in all cases. That semen and hormone abnormalities were observed in both the fertile and infertile men with varicoceles suggests that the presence of a varicocele is associated with some degree of primary testicular dysfunction, regardless of present fertility status. PMID- 3096788 TI - Prevention of gonadotropin-releasing hormone antagonist induced luteal regression by concurrent exogenous pulsatile gonadotropin administration in monkeys. AB - We studied the effects of a gonadotropin-releasing hormone (GnRH) antagonist given in midluteal phase. Monkeys received the antagonist (n = 6), [N-Ac-D-p-Cl Phe1,2,D-Trp3,D-Arg6,D-Ala10]-GnRH: hydrochloride or vehicle (n = 5). Absent luteinizing hormone (LH) pulsatility, diminished progesterone (P) secretion (P less than 0.01), luteal phase truncation and premature menstruation were observed in all receiving the antagonist. To investigate the site of action, four females received pulsatile exogenous human menopausal gonadotropins (hMG) concurrently, whereby P secretion was sustained and premature menstruation was averted. Equivalent treatment using "pure" FSH, failed to sustain P levels and timely menstruation occurred, confirming the continuing dependence of the corpus luteum on LH. The antagonist acts by central suppression and in turn, diminishes P biosynthesis. LH is luteotropic, since pulsatile LH (hMG), not "pure" FSH, prevented luteolysis. PMID- 3096789 TI - Pregnancy induced with menotropins in a woman with polycystic ovaries, endometrial hyperplasia, and adenocarcinoma. AB - A 31-year-old woman is described with PCOD associated with endometrial hyperplasia and well-differentiated adenocarcinoma. Conservative treatment with ovulation induction was pursued for a total of 3 1/2 years. After CC treatment failed to achieve conception, treatment with menotropins resulted in a twin pregnancy that aborted spontaneously and a singleton term pregnancy. Hysterectomy was performed 4 1/2 years after the initial diagnosis of well-differentiated endometrial adenocarcinoma was made. Histologic examination of the endometrium showed no progression of the disease. Ovulation induction of patients with polycystic ovaries and well-differentiated and noninvasive endometrial adenocarcinoma may be justified in properly selected cases. PMID- 3096790 TI - Effects of sulpiride-induced hyperprolactinemia on human ovarian follicles during the late follicular phase. AB - The effect of hyperprolactinemia during the midfollicular through the late follicular phase of the menstrual cycle on follicular development and follicular fluid hormone concentrations was studied. Fourteen women underwent laparotomy in the late follicular phase for gynecologic reasons; 6 were treated with sulpiride daily from the midfollicular to the late follicular phase (sulpiride group) and 8 received no treatment (control group). Daily administration of sulpiride (150 mg orally) significantly elevated serum prolactin (PRL) levels in all six women. In the small follicles (less than or equal to 8 mm in diameter), follicular fluid 17 beta-estradiol (E2) concentration was significantly lower (P less than 0.01), and testosterone (T) concentration was higher (P less than 0.05) in the sulpiride group. In the large follicles (greater than or equal to 9 mm in diameter), however, follicular fluid E2 and T concentrations showed no significant differences between the sulpiride and control groups. In the sulpiride group, the mean diameters of the follicles were significantly smaller than in the control group (P less than 0.01). These observations suggest that PRL exerts a suppressive effect on the smaller but not the larger follicles during the late follicular phase. PMID- 3096791 TI - Ovarian follicular maturation in women. I. Intermittent versus daily administration of human menopausal gonadotropin. AB - This study was designed to compare the efficiency of daily intramuscular human menopausal gonadotropin (hMG) therapy to an intermittent subcutaneous regimen in women with ovulatory dysfunction. Ovarian follicular development was assessed with the use of serial ultrasound scans and serum 17 beta-estradiol (E2) levels. Ovulation was based on pregnancy and/or elevated luteal progesterone values. There were no significant differences between the two treatment regimens, based on E2 levels, follicular size, and/or number of follicles greater than 1.0 cm. Pregnancy and ovulation occurred more frequently after intramuscular hMG therapy. These results indicate that daily hMG is preferred over intermittent subcutaneous administration because of convenience. PMID- 3096793 TI - Molecular composition of luteinizing hormone and follicle-stimulating hormone in commercial gonadotropin preparations. AB - The biologic (B) and immunologic (I) properties of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in three commercial urinary gonadotropin preparations and in the first international standard preparation of human urinary gonadotropins before and after fractionation by isoelectrofocusing (IEF). Significant differences were found in the IEF profiles of both bioactive and immunoreactive LH and FSH and in the B/I ratios of the preparations studied. The observed differences in the molecular composition of LH and FSH seem to be attributable to the purification procedures employed. The possible influence of these differences on the in vivo potencies, circulating half-lives, and clinical effects of gonadotropin preparations are discussed. PMID- 3096792 TI - Ovulation induction with pulsatile luteinizing releasing hormone in women with clomiphene citrate-resistant polycystic ovary-like disease: clinical results. AB - Eighty-four treatment units were given to 11 women with clomiphene citrate resistant polycystic ovarian disease (PCOD). PCOD was defined as oligomenorrhea elevated luteinizing hormone (LH), normal follicle-stimulating hormone (FSH), and preference-elevated androgens. Luteinizing-releasing hormone (LRH) was administered intravenously via a portable infusion pump. Doses varied between 5 and 40 micrograms/pulse given at 60-, 90-, or 120-minute intervals. In 11 women, 85 treatment units (TUs) were completed, of which 74 were ovulatory, showing no specific advantage of any particular pulse dose or pulse interval. Five pregnancies occurred in three women. Two women did not ovulate during 52 and 284 consecutive days of therapy, respectively. Oligomenorrheic patients with PCOD can be made more regular by means of LRH, not necessarily leading to a regular menstrual cycle. In general, LRH is sufficient for luteal support. No signs of hyperstimulation were observed, although two patients incidently developed unilocular cysts with a maximum diameter of 8 cm. Ovulation induction with LRH in PCOD is possible, although the disease itself does not change during therapy. This may be further evidence that altered hypothalamic LRH secretion is more the result, rather than the cause, of the phenomenon of PCOD. PMID- 3096795 TI - Characteristics of ovarian follicles in spontaneous and stimulated cycles in which there was an endogenous luteinizing hormone surge. AB - The growth of ovarian follicles was assessed with the use of ultrasound in spontaneous cycles and in cycles stimulated with clomiphene citrate (CC) alone, CC plus pulsatile human menopausal gonadotropin, and CC plus pulsatile follicle stimulating hormone (FSH). At the time of the onset of the luteinizing hormone surge (LH), the size of the leading follicle did not differ significantly between the spontaneous and the stimulated cycles, although it was larger in the CC/FSH cycles. During the two days before the LH surge onset, the growth rate was faster in the stimulated than the spontaneous cycles. It is suggested that despite the provocation of extremely high plasma-estradiol levels and multiple follicular development, the leading follicle in stimulated cycles ovulated at a size equal to or greater than that in spontaneous cycles. The reason for the higher follicle size in the CC/FSH cycles is, as yet, unclear. PMID- 3096794 TI - Dieting influences the menstrual cycle: vegetarian versus nonvegetarian diet. AB - Eighteen healthy, normal-weight women aged 19 to 27 years who had regular ovulatory menstrual cycles volunteered for the study. Blood was drawn on Mondays, Wednesdays, and Fridays throughout the control cycle and during a 6-week diet period that began with commencement of a new cycle. Nine women followed a vegetarian diet and nine a nonvegetarian diet. Both groups lost an average of 1 kg body weight/week. Seven of nine women in the vegetarian group became anovulatory. During the vegetarian diet the average luteinizing hormone (LH) values were significantly decreased during the midcycle and the luteal phase. Estradiol (E2) and progesterone (P) values were significantly lower during the luteal phase. In contrast, the nonvegetarian group did not show significant reduction of LH, E2, and P values during any part of the menstrual cycle. Seven of nine women in the nonvegetarian diet group maintained ovulatory cycles with no changes in cycle length or in the length of the follicular phase. In one woman who became anovulatory, E2 values did not increase during the follicular phase. PMID- 3096796 TI - [Characteristics of circulation, ventilation and gas exchange in intact and anesthetized dogs]. AB - Light hexenal anesthesia was found not to affect the mean values of hemodynamics and O2 tension in the blood but increased the CO2 tension in arterial blood and decreased the oxyhemoglobin content and pH of the blood in dogs. PMID- 3096797 TI - [Water and electrolyte metabolism in the isolated rumen of sheep after carbonic anhydrase inhibition]. AB - The exchange of mineral and low-molecular organic ions through the wall of the sheep temporarily isolated forestomach in carbonic anhydrase inhibition, were studied. The physiological significance of carbonic anhydrase for absorption of some ions in the rumen is discussed. PMID- 3096798 TI - [Effects of intranasal administration of LHRH superanalogue on endogenous LHRH and gonadotropins in humans]. AB - Plasma LH, FSH and endogenous LHRH were determined by radioimmunoassay (RIA) when 100 micrograms of LHRH superanalogue, des-Gly10-[D-Leu6]-LHRH ethylamide (leuprolide) was intranasally administered to both 7 healthy subjects aged 22 to 63 years and 6 patients with various hypogonadism aged 22 to 43 years [2 with anorexia nervosa, 3 with hypophysial hypogonadism and 1 with isolated gonadotropin (Gn) deficiency]. The response of plasma LH after the intranasal administration of leuprolide was observed to be 814 +/- 236 (mean +/- SE)% in the healthy subjects at 2 to 10 hours, and 528 +/- 183% in the patients with hypogonadism at 2 to 4 hours. These elevations were observed until 24 hours after administration in both groups. The response of plasma FSH was observed to be 449 +/- 99% in the healthy subjects at 3 to 8 hours, and 593 +/- 238% in the patients with hypogonadism at 2 to 6 hours. These elevations were observed until 24 hours in the healthy subjects and until 12 hours in the patients with hypogonadism. Furthermore, these responses tended to be higher than those after 100 micrograms intravenous administration of LHRH; LH responded up to 386 +/- 50% in the healthy subjects and up to 390 +/- 91% in the patients with hypogonadism, and FSH up to 282 +/- 38%, 343 +/- 90%, respectively. The elevation of plasma immunoreactive LHRH which was determined using RIA having no immunocrossreactivity with leuprolide (less than 0.01%) was observed at 6 hours after the administration of leuprolide in the healthy subjects (789 +/- 497%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096799 TI - Localization of immunoglobulin-containing cells in human endometrium in the first trimester of pregnancy and throughout the menstrual cycle. AB - The distribution of immunoglobulins in normal human endometrium throughout the menstrual cycle and in early pregnancy has been studied with an immunoperoxidase technique. In first-trimester decidua, IgG was detected within many cells of differing morphology and size. Large IgG-containing cells were often binucleate and were believed to be decidual cells. Examination of serial sections showed no kappa or lambda light-chain restriction, suggesting absorption of the immunoglobulin content. Medium-sized, irregular, IgG-containing cells were macrophages. An additional substantial population of small hyperchromatic IgG containing cells were prominent around arterioles and adjacent to endometrial glands. From examination of adjacent sections stained with phloxine tartrazine, it was concluded that these represented endometrial granulocytes. Labelling for light chains again suggested absorption of the immunoglobulin content. In contrast, in non-pregnant endometrium immunoglobulin-containing stromal cells were uncommon, although IgG and IgA were detected in gland epithelium and secretions and in the stromal interstitium particularly in the secretory phase. These results support the notion that human endometrium lacks a classical secretory immune system and highlight the requirement for correlation between studies of cell surface markers, morphology and cell surface receptors. PMID- 3096800 TI - Spatial and temporal relationships between vinculin and talin in the developing chicken gizzard smooth muscle. AB - The spatiotemporal relationships between vinculin and talin in developing chicken gizzard smooth muscle were investigated. Immunofluorescence and immunoelectron microscopic labeling revealed that both proteins are associated with membrane bound dense plaques in muscle cells; however, the most intense labeling for vinculin was located rather closer to the membrane than that for talin. The localization of vinculin and talin in embryonic chicken gizzards indicated that both are primarily cytoplasmic during the first 2 embryonic weeks. Only around days 16-18 does talin apparently become associated with the plasma membrane, this being concomitant with the appearance of distinct myofilament-bound dense plaques. Vinculin, on the other hand, remains primarily cytoplasmic and appears in the plaques only 1-3 days after hatching. It is thus proposed that the interactions of the dense plaque with myofilaments or with the membrane do not depend on the presence of vinculin in the plaque. Electrophoretic analyses indicated that, during development, there is no major change in the differential expression of specific vinculin isoforms. Quantitative immunoblotting analysis indicated that the vinculin content (relative to total extracted protein) is virtually constant during the last week of embryonic life. However, within 3 days of hatching, the vinculin concentration increases remarkably to over twice the embryonic level, and then slowly increases until it reaches the adult levels, which are three to four times higher than the embryonic level. The concentration of metavinculin (a 160-Kd vinculin-related protein) showed only a limited increase after hatching. We discuss the possible roles of vinculin and talin in the assembly of membrane-bound dense plaques during the different phases of smooth-muscle development. PMID- 3096801 TI - Immunocytochemical localization of extracellular-matrix proteins in relation to rat intestinal morphogenesis. AB - Various extracellular-matrix proteins were detected by indirect immunofluorescence in rat intestine at various stages of development ranging from 14 days of gestation to the adult stage. At the earliest stage studied, laminin, nidogen and type-IV collagen were present at the epithelial/mesenchymal interface, whereas fibronectin and type-III procollagen were found throughout the whole mesenchyme. We were able to relate some changes in the staining patterns of extracellular-matrix proteins to morphogenetic processes. As early as 15 days of gestation, i.e. before villus formation, modifications in the distribution or in the staining intensity of all of the antigens within the mesenchyme paralleled the orientation and segregation of mesenchymal cells in the region surrounding the basal membrane and in the presumptive peripheral muscular layers. During villus outgrowth, the transient disappearance of fibronectin and particularly type-III procollagen from the top of the protruding villus core was evident. During the perinatal period, i.e. when crypts develop, the linear staining for the basal-membrane proteins became restricted to the base of the villi, their labelling along the remaining portion of the villi being more irregular. In mature rat intestine, no major modifications in matrix proteins along the crypt villus axis in relation to epithelial differentiation were found, except that the labelling for fibronectin and type-III procollagen, which are at this stage more closely related to the basement membrane, was less pronounced in the upper part of villi. PMID- 3096802 TI - Butyrate-induced cell differentiation of cell-cycle mutants and 'wild-type' mastocytoma cells: histamine, 5-hydroxytryptamine and metachromatic granules as independently regulated differentiation markers. AB - In cultures of heat-sensitive (hs; arrested at 39.5 degrees C, multiplying at 33 degrees C) and cold-sensitive (cs; arrested at 33 degrees C, multiplying at 39.5 degrees C) cell-cycle mutants that had been isolated from the same subclone (K21) of the murine P-815-X2 mastocytoma line, the degree of cell differentiation was assessed by determining the cellular histamine and 5-hydroxytryptamine (5-HT) content as well as the number of metachromatic granules per cell. The findings were compared with those obtained for 'wild-type' K21 and P-815-X2 cells. The addition of butyrate to 'wild-type' cells or to mutant cells maintained at the respective permissive temperature resulted in a relative increase in the level of all three differentiation markers. In cs mutant cells, essentially the same pronounced increase in granule numbers was observed during butyrate treatment at 39.5 degrees C and during incubation at 33 degrees C without butyrate, thereby suggesting that butyrate induces morphological cell differentiation in cs mutants via the same mechanisms as exposure to the nonpermissive temperature. In contrast, the histamine and 5-HT levels reached in hs and cs mutant cells in the presence of butyrate were higher than those observed during incubation at the nonpermissive temperature. Large quantitative differences were detected with respect to the potential of individual cell lines to express the three differentiation parameters. High levels of histamine were characteristic of 'wild type' P-815-X2 cells treated at 33 degrees C with butyrate, while low amine levels and small numbers of granules were observed in K21 cells (i.e., the parent line of hs and cs mutants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096803 TI - Mechanisms for the release and redistribution of 2,4,5,2',4',5' hexachlorobiphenyl (6-CB) from hepatic tissues in the rat. AB - The translocation of 6-[14C]CB from rat hepatic tissues to various media was studied employing in situ hepatic perfusion and primary hepatocyte culture techniques. 6-[14C]CB release from the hepatic tissues of female rats pretreated with 2 microCI 6-CB was dependent on the relative proportion of perfusate buffer components. Approximately 10% of hepatic 6-CB was released into buffer containing either 4% BSA or 4% BSA and 100 mg/dl exogenous human very low density lipoproteins (VLDL). 6-CB release was significantly increased under simulated hyperlipidemic conditions (400 mg VLDL/dl). Release declined when BSA was eliminated or replaced with Dextran. The distribution of 6-CB between the triacylglycerol (TG)-rich VLDL and the protein buffer components was found to be dependent on the ratio of TG:protein. Under hyperlipidemic perfusate conditions, approximately 83% of the 6-CB associated with the BSA fraction. Under normolipidemic conditions, 99% of the 6-CB associated with BSA. The concentration of 6-CB in TG was greatly increased under hyperlipidemic conditions. Thus, 6-CB distribution under simulated normolipidemic conditions could not be explained by saturation of the VLDL fraction. Approximately 15% of 6-CB was released from hepatocytes prepared from late pregnant or age-matched control rats. Eighty percent of 6-CB was associated with VLDL secreted from hepatocytes. The TG:protein ratio in culture media was approximately 1: 6 while ratios of 1:20 or 1:600 occurred in the perfusion studies. These data suggest that 6-CB may be released from hepatic tissues in association with newly synthesized TG, but that once in the circulation, its distribution is dependent on the ratio of TG to protein present. PMID- 3096804 TI - [Bacterial endocarditis after endoscopic polypectomy]. PMID- 3096805 TI - Effect of teprenone on the content of phospholipids in gastric secretion in man. AB - The phospholipid content of basal and pentagastrin-stimulated gastric secretion was measured in 9 healthy volunteers. One week oral administration of teprenone did not alter the gastric acid and pepsin secretion. The phospholipid content was increased by teprenone. Changes in subclasses of phospholipids in gastric mucus by teprenone treatment, namely, increased phosphatidylcholine and decreased lysophosphatidylcholine, were observed. PMID- 3096806 TI - Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. AB - We studied the effect of 1 yr of parenteral nutrition on liver function tests and, when indicated, liver histology and ultrastructure of 18 patients with no (n = 6), modest (n = 6), and massive (n = 6) loss of intestine. The resection was for Crohn's disease and infarction, respectively. The liver function tests remained normal in all patients with no loss and modest loss of intestine. Four patients with massive loss of intestine, 4-10 mo after initiation of parenteral nutrition, began to develop progressive, marked increases in serum alkaline phosphatase (2-10 times normal), glutamic oxaloacetic transaminase (7-20 times normal), and glutamic pyruvic transaminase (5-14 times normal) activity levels, and bilirubin concentration (5-22 times normal). Light microscopic examination of liver showed cholestasis, bile ductular proliferation, periportal inflammation, fibrosis, and mild steatosis. Electron microscopic examination of liver showed cholestasis with nonspecific organelle changes. None of the patients had any evidence of extrahepatic obstruction. Our data suggest that massive loss of intestine is a contributing factor to hepatic cholestasis and fibrosis in patients maintained on prolonged parenteral nutrition. PMID- 3096807 TI - Hepatic neurofibromatosis, malignant schwannoma, and angiosarcoma in von Recklinghausen's disease. AB - Liver involvement by neurofibromatosis is rare. This report describes a young man with von Recklinghausen's disease and hepatic neurofibromas who developed a large right hepatic lobe malignancy and died of massive intratumor hemorrhage. Postmortem examination showed the tumor to be composed of both malignant schwannoma and angiosarcoma and to have arisen from contiguous neurofibromas in portal tracts. Widespread pulmonary metastases consisted of the angiosarcomatous elements alone. The expression of malignant schwannoma and angiosarcoma phenotypes in this tumor may be related to a common histogenesis from cells of the neural crest. PMID- 3096808 TI - Effects of cadmium ions, D-600 and chlorpromazine on the skinned smooth muscle of guinea-pig taenia coli. AB - The effects of Cd2+ on the skinned taenia coli were compared with that of Ca2+ channel blocker, D-600 and calmodulin inhibitor, chlorpromazine. The Cd2+ (0.001 0.5 mM) inhibited the contraction of skinned fibres in a dose-dependent manner. In contrast, the contraction of skinned fibres was not inhibited by pretreatment with 1 X 10(-6) M D-600. However, chlorpromazine (10(-4) M) inhibited the contraction of skinned taenia coli. The inhibition of contraction by Cd2+ in skinned taenia coli was completely reversed by washing with solution containing EDTA, following a treatment with 0.5 mM Cd2+ for 15 min. The skinned fibres had rapidly taken up a far greater amount of Cd2+ than intact muscle of taenia coli. EDTA increased Cd2+ efflux in skinned fibres and only 5% of the original tissue content retained. Thus, EDTA, which was ineffective on intact taenia coli, can be considered to act on Cd2+ of intracellular compartment after disruption of the cell membrane with saponin. In conclusion, there is the possibility that Cd2+ inhibits the contractile system, such as contractile proteins and calmodulin, which results in tension inhibitory effect. PMID- 3096809 TI - The effect of 6-hydroxydopamine pretreatment on the metabolic response produced by endotoxin in rabbits. AB - The thermoregulatory, effector processes were investigated in rabbits after treatment with 6-hydroxydopamine (6-OHDA) and lipopolysaccharide Escherichia coli (LPS). Pyrogen (1 microgram/kg, i.v.) produced a fever reaction resulting from stimulation of the metabolic rate and heat conservation responses. Pretreatment with 6-OHDA (3 X 500 micrograms, i.c.v.) reduced the metabolic as well as pyretic activity of pyrogen. It is suggested that stimulation of the thermoregulatory heat production which contributes to the febrile rise in body temperature is dependent on the intact adrenergic structures in the central nervous system. PMID- 3096810 TI - Modulation of the prolactin response to thyrotropin releasing hormone by ovarian steroids in ovariectomized turkeys (Meleagris gallopavo). AB - The effect of thyrotropin releasing hormone (TRH) administered intramuscularly (im) on serum levels of prolactin (Prl) in ovariectomized (ovx) adult turkeys before and following the onset of photostimulation, before and during daily administration (im) of progesterone (P; 0.1, 0.4, or 1.0 mg/kg), estradiol benzoate (EB; 0.01, 0.1, or 0.2 mg/kg), or their combination (1.0 mg/kg EB + 0.1 mg/kg P) were studied. Ovariectomy reduced Prl levels in the serum of photostimulated turkeys, and blunted the Prl response to TRH administration. Progesterone treatment had no effect on basal serum Prl levels but the Prl response to TRH was higher in P-treated turkeys than in non-treated ovx turkeys. Basal serum Prl levels were higher (P less than 0.05) in the EB-treated ovx turkeys than in the untreated birds. The Prl response to TRH in ovx EB-treated turkeys was greatly increased (P less than 0.05). Progesterone treatment of EB primed ovx turkey did not alter the basal levels of serum Prl or the Prl response to TRH administration. These results suggest that ovarian steroids may be responsible for the increased Prl secretion in the female turkey associated with laying. PMID- 3096811 TI - Annual cycles of gonadotropins and androgens in the hibernating golden-mantled ground squirrel. AB - Ground squirrels, captured in the field, were housed at ambient temperatures of 23 degrees (photoperiod = 10L:14D) for 13 months. Plasma was sampled at 3 to 4 week intervals and measured for gonadotropin and androgen levels. Testis size was examined monthly by laparotomy. Male ground squirrels showed clear circannual cycles in body mass, testis size, and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), and dihydrotestosterone (DHT). During summer and fall, FSH, LH and androgen levels were low, testes were undeveloped, and body mass was increasing. Testes began to rapidly enlarge in January and reached maximum size in February. A rise in FSH preceded gonadal growth but LH remained low until near the time of testis mass peak. LH remained elevated during spring while FSH levels fell and testes regressed. Plasma T and DHT levels generally paralleled LH concentrations; DHT levels were approximately one-fifth those of T levels. During winter animals lost weight but were only occasionally found in a slightly hypothermic condition. Females had elevated plasma LH levels (greater than 1 ng/ml) predominantly in the spring but displayed no cycle in plasma FSH levels. A second group of males held at 4 degrees for 8 months (photoperiod = stimulated natural for 47 degrees N) were regularly torpid during a hibernation season that lasted between November and May. Most (15/21) of these males did not show gonadal development by spring; these non-reproductive males had had restricted body mass gains the previous fall. Plasma FSH was low in both reproductive and non-reproductive males during fall and winter but increased in March while animals were still hibernating. FSH levels continued to increase in April only in reproductive males and reached maximal levels after hibernation was spontaneously terminated. LH titers were elevated in individual males in winter during torpor and were greater in reproductive than in non-reproductive males in May. Androgen levels were undetectable in torpid squirrels, elevated in animals sampled during periodic arousals, and elevated in most males within 3 weeks after terminating hibernation. PMID- 3096812 TI - Ovarian steroidogenesis in vitro during the first month posthatching in the domestic chick: gonadotropin responsiveness and [3H]progesterone metabolism. AB - Ovarian steroidogenesis was examined in domestic chicks during the first month posthatching. In vitro production of androstenedione during a 4-hr incubation was enhanced in a dose-dependent manner by 0.1-100 ng/ml of chicken LH (cLH). The greatest response was observed in ovaries from Day 1 chicks (eightfold), but cLH was also effective in Day 7, 14, 21, and 28 ovaries (three- to sixfold increase). Estrogen production in response to cLH was increased significantly only in Day 1 and 7 ovaries. A similar trend in androstenedione and estrogen production was seen in response to 8-bromo cAMP, oLH, and oFSH. In an additional experiment, in vitro metabolism of [3H]progesterone by ovaries from Day 1, 7, 14, and 21 chicks was examined during a 4-hr incubation. The major metabolite, comprising 18-19% of the radioactivity, coeluted with 5 beta-pregnan-3,20-dione. This is the first report of gonadotropin-stimulated steroidogenesis and progesterone metabolism in the chick during the first month post-hatching. The results show that the responsiveness to gonadotropins decreases during this period and the profile of [3H]progesterone metabolism does not resemble that seen in adult granulosa and theca cells. PMID- 3096813 TI - Estradiol-17 beta and thyrotropin-releasing hormone stimulate prolactin release from the pituitary gland of a teleost fish in vitro. AB - The effects of estradiol-17 beta (E2) and thyrotropin-releasing hormone (TRH) on prolactin (PRL) release were investigated using the organ-cultured rostral pars distalis (RPD) of the tilapia, Oreochromis mossambicus. Spontaneous PRL release into hyperosmotic medium increased in a dose-related manner following E2 pretreatment in vitro. In addition, TRH stimulated a dose-related increase in PRL release from E2-preincubated RPD's, but had no effect on tissues not previously exposed to E2. The maximal PRL response, nearly three times control levels, occurred at 50 nM TRH. Higher doses of TRH were less effective in stimulating PRL release. These findings indicate that TRH may be an important hypothalamic prolactin-releasing factor in the tilapia. Furthermore, the marked potentiation of the action of TRH on PRL release following exposure to E2 suggest that there may be a shift in the control of PRL secretion with changes in the reproductive state of the tilapia. PMID- 3096814 TI - Effects of temperature and mode of delivery on responses to gonadotropin releasing hormone by superfused frog pituitaries. AB - An in vitro superfusion system was used to examine the effects of temperature on the responsiveness of frog, Rana pipiens, hemipituitaries to chronic superfusion with gonadotropin-releasing hormone (GnRH). The effects of pulsatile as opposed to continuous delivery of GnRH on luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion were also studied at 30 degrees. Secretion of both gonadotropins (FSH and LH) increased significantly in a dose-dependent manner in response to a brief exposure to 0.1-1000 ng/ml (nM) GnRH at both 18 and 32 degrees, but the magnitude of response at each dose was temperature dependent. Moreover, the temporal pattern of the chronic response to a standard dose of GnRH (100 ng/ml) also varied markedly between 10 and 32 degrees: Hemipituitaries superfused at 10 or 18 degrees showed greatly attenuated responsiveness to GnRH after the first hour of GnRH treatment, whereas responsiveness was maintained or even continued to increase for many hours at higher temperatures. These temperature effects may be related to seasonal changes in reproductive activity. Pulsatile administration of GnRH was more effective in inducing elevated gonadotropin (GtH) secretion during the first few hours of superfusion, but continuous superfusion with GnRH was more effective at maintaining elevated GtH levels over long periods. The results support and extend previous studies by indicating that, unlike the situation in many mammals and birds, the frog pituitary is highly resistant to desensitization by even high doses of GnRH, and in fact, self-priming and maintained responsiveness to GnRH is better supported by chronic treatment than by pulsatile delivery of GnRH. PMID- 3096815 TI - Annual cycles of plasma gonadotropins and sex steroids in Japanese common pheasants, Phasianus colchicus versicolor. AB - Plasma levels of FSH, LH, and sex steroid hormones were monitored individually in 5 male and 15 female Japanese common pheasants once to thrice monthly for 13 months. The birds were reared in outdoor cages, each containing 1 male and 5 females, under natural conditions of temperature and photoperiod. Around the period of egg laying from April 19 to July 6, plasma levels of FSH, LH, estradiol 17 beta (E2), and progesterone (P) in females were high. The increases in circulating FSH and E2 occurred earlier (in March) than those in LH and P (from April to May); decreased levels were observed first for LH in mid-June, second for P and E2 in late June, and last for FSH in June to August. Regression analysis revealed that the temporal course in titer of E2 is better rationalized as being dependent on the level of FSH rather than LH, whereas that of P is more dependent on LH than on FSH. In males, FSH was elevated only in March to June, whereas the temporal course of plasma levels of LH was clearly bimodal with maxima in February and in September. The titer of testosterone (T) was high in March to June, coinciding approximately with the maximum level of FSH. FSH was positively correlated with T, whereas LH was not in a simple correlation analysis. However, multiple-correlation analysis revealed that the change in T was better explained by considering the influence of both FSH and LH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096816 TI - Linkage analysis of Von Recklinghausen neurofibromatosis: chromosomes 4 and 19. AB - This report describes a study that examines the hypotheses of genetic linkage between the autosomal dominant disorder neurofibromatosis (NF) and loci on human chromosomes 4 and 19. Twelve Utah families were evaluated for evidence of possible linkage of NF to six known markers on chromosome 4 and five markers on chromosome 19. Due to previous reports suggesting tight linkage of NF to the GC locus on chromosome 4 and the C3 (linked to myotonic dystrophy) locus on chromosome 19, these two markers were of particular interest. For the Utah families the cumulative LOD score for GC was -4.81 (r = 0.05). Cumulative LOD scores were -0.90 (r = 0.05) and -1.01 (r = 0.05) for C3 serum determinations and a C3 DNA polymorphism respectively. Linkage data is also included on all individual informative families for the GC and C3 loci to specifically address the question of heterogeneity. Linkage data is consistent with, but does not strongly support, the existence of heterogeneity implicating both the GC locus on chromosome 4 and the C3 locus on chromosome 19. A compilation of cumulative LOD scores from this and other current linkage studies produces values that in the absence of heterogeneity refute previous reports for tight linkage of NF to GC and to C3. PMID- 3096817 TI - Fitness as a function of beta-galactosidase activity in Escherichia coli. PMID- 3096818 TI - Structure of the gene encoding the exoglucanase of Cellulomonas fimi. AB - In Cellulomonas fimi the cex gene encodes an exoglucanase (Exg) involved in the degradation of cellulose. The gene now has been sequenced as part of a 2.58-kb fragment of C. fimi DNA. The cex coding region of 1452 bp (484 codons) was identified by comparison of the DNA sequence to the N-terminal amino acid (aa) sequence of the Exg purified from C. fimi. The Exg sequence is preceded by a putative signal peptide of 41 aa, a translational initiation codon, and a sequence resembling a ribosome-binding site five nucleotides (nt) before the initiation codon. The nt sequence immediately following the translational stop codon contains four inverted repeats, two of which overlap, and which can be arranged in stable secondary structures. The codon usage in C. fimi appears to be quite different from that of Escherichia coli. A dramatic (98.5%) bias occurs for G or C in the third position for the 35 codons utilized in the cex gene. PMID- 3096819 TI - Molecular cloning of the phosphoenolpyruvate carboxylase gene of Anabaena variabilis. AB - Purified Anabaena variabilis chromosomal DNA was partially digested with restriction endonuclease Sau3A and ligated into the BamHI site of plasmid pBR322. Escherichia coli 342-167, a mutant with a decreased level of phosphoenolpyruvate carboxylase (PEPCase) activity was transformed with plasmids from the A. variabilis genomic library. A transformant that grew on minimal media in the absence of glutamate was isolated and its plasmid, pTRH1, was shown to encode the A. variabilis PEPCase. E. coli HB101 cells transformed with plasmid pTRH1 have approx. 50 times the normal amount of PEPCase activity and also overproduce a protein with the apparent Mr (99,000) of the A. variabilis PEPCase. PMID- 3096820 TI - CHAP II therapy for epithelial ovarian cancers following primary treatment with platinum-based combination chemotherapy. AB - Nineteen patients with stage III or IV epithelial ovarian cancer treated on a prospective randomized protocol with either adriamycin and cis diamminedichloroplatinum or tamoxifen, adriamycin, and cis diamminedichloroplatinum received a modified "CHAP II" regimen at the time of clinical progression of disease or the finding of occult cancer at second-look surgery. One patient had a clinical complete response lasting 6 months, one had a partial response lasting 23 months, 6 had clinically stable disease for an average of 6.5 months (range 4-15 months), 8 patients had progressive disease, and 3 patients without clinically detectable disease remained disease free for a mean time of 10 months (range 7-16 months). The modified "CHAP II" regimen employed in this study for patients failing prior cis-diamminedichloroplatinum based regimens appears to have only limited efficacy in inducing objective remissions. PMID- 3096821 TI - Immunological and molecular classification of acute lymphoblastic leukemia. PMID- 3096822 TI - Ultrastructural findings in the bone marrow of a patient with true histiocytic lymphoma. PMID- 3096823 TI - Solid leukemic intracerebral deposits in patients with acute leukemia. PMID- 3096824 TI - T-cell depletion with the monoclonal antibody Campath 1 to prevent graft-versus host disease in ten high-risk adult patients. PMID- 3096825 TI - Massive pulmonary calcification in multiple myeloma. Report of a case. PMID- 3096826 TI - A case of Am, a rare variant in the ABO blood group system. PMID- 3096828 TI - Primary Hodgkin's lymphoma of the sigmoid colon. PMID- 3096827 TI - Terminal deoxynucleotidil transferase (TdT) activity in human leukemia. Quantitative evaluation with enzymatic immunoassay (EIA). PMID- 3096830 TI - Myelofibrosis: a role for platelet derived growth factor (PDGF)? PMID- 3096829 TI - Myasthenia gravis associated with atrophic gastritis type A and iron deficiency. PMID- 3096831 TI - Histopathology of bone marrow metastases. Considerations on 104 cases. PMID- 3096832 TI - T lymphocyte content in blood components. PMID- 3096833 TI - Microcytic anemia in rheumatoid arthritis. Relationship with activity and duration of the disease and iron status. PMID- 3096834 TI - Synthesis of thrombospondin and glycoprotein IIb-IIIa by a purified megakaryocyte human bone marrow culture. PMID- 3096835 TI - Anemia in hypopituitarism: evidence of hormone-dependent qualitative abnormalities of erythropoiesis. PMID- 3096836 TI - The definition of the favourable stage of CLL. PMID- 3096837 TI - Antithrombin III deficiency as congenital risk factor for venous thrombosis and embolism. PMID- 3096838 TI - A case of idiopathic myelofibrosis with poorly differentiated circulating blasts. The role of the fixative in the peroxidase reaction. PMID- 3096839 TI - Monoclonal gammopathy of undetermined significance in a case of primary thrombocythemia. PMID- 3096840 TI - Terminal deoxynucleotidyl transferase: a nuclear marker of hemopoietic precursors. Biochemical, immunological and clinical aspects. PMID- 3096841 TI - Intracytoplasmatic and intranuclear filamentous inclusions in a case of acute monocytic leukemia. PMID- 3096842 TI - Prenatal diagnosis of hemophilia by fetal blood sampling under ultrasound guidance. AB - In utero fetal blood sampling was performed in 55 cases for prenatal diagnosis of hemophilia A and B. Fifteen fetuses were found to be affected. However, with this new procedure, it was possible to demonstrate that fetuses were not hemophiliacs in 40 cases. Therefore, pregnancy was not interrupted; these infants were born and definitely proven to be normal. There were no diagnostic errors. PMID- 3096843 TI - Salicylate antagonism of acetylsalicylic acid inhibition of platelet aggregation in male and female subjects: influence of citrate concentration. AB - Platelets from volunteers were exposed for 1 min to sodium salicylate (SA) before and after the addition of acetylsalicylic acid (ASA) to produce greater than or equal to 50% inhibition of aggregation induced by arachidonic acid (AA) or collagen. SA:ASA concentrations = 20:1. SA protection against ASA inhibition was always observed even if ASA exposure time was 15 min, whereas reversal could not be demonstrated once exposure of platelets to ASA exceeded a minimum of 3-10 min with AA as the stimulus. Reversal was even less effective when collagen was the stimulus. An apparent, increased sensitivity to SA reversal of ASA inhibition in females disappeared when citrate concentration was adjusted to compensate for lower packed cell volume. The proposed male dependency for protection in ASA treatment of thromboembolic disorders cannot be explained on the basis of differences in the SA-ASA competition at platelet cyclooxygenase and, if collagen is an important in vivo stimulus of platelet interaction with damaged vessel wall, the antagonism of ASA by SA may not be important. PMID- 3096844 TI - Primary lymph node plasmocytoma of IgD-class. AB - An extramedullary plasmocytoma in a right inguinal lymph node was observed in a 62-year-old woman. The tumor showed monoclonal proliferation of plasma cells which revealed highly positive stainings of both IgD and lambda light chain using the PAP-technique. Monoclonal IgD-lambda was also secreted in serum and urine. Clinical data, lymphography and bone biopsy showed a tumor spreading in the right inguinal, left iliacal and lumbar regions without systemic involvement of bone. In contrast to extramedullary plasmocytomas of other immunoglobulin classes the disease progressed rapidly and the patient died 8 months after the onset. The present case is the first reported IgD-plasmocytoma in lymph nodes. PMID- 3096845 TI - [Lupus anticoagulant]. PMID- 3096846 TI - Bureaucracy's impact on decision making in long-term care. AB - Are decisions about the most effective services for a client influenced by factors other than the client's needs, available resources, and the social worker's skill and judgment? This study of social workers in two social welfare agencies in Israel examines how practice settings affect workers' decisions and suggests that environmental variables have a pervasive impact. PMID- 3096848 TI - Investigation of coffee in Drosophila genotoxicity tests. AB - Two preparations of coffee (instant coffee and freeze-dried home-brew coffee) were tested in different mutagenicity assays in germ cells as well as in somatic cells of Drosophila melanogaster. The three end-points assayed in germ cells were sex-linked recessive lethals (mainly gene mutations and small chromosome aberrations), dominant lethals (cytotoxic effects as well as genotoxic effects) and sex-chromosome losses (chromosome breakage and non-disjunction). The aqueous coffee solutions were fed either to adult male flies for 3 days or to growing larvae during the whole larval development. Treated males were crossed with appropriately marked females, and the different genetic end-points were analysed in the F1 or F2 generation. The test concentrations (instant coffee 4% (w/v), home-brew coffee 3%) were acutely toxic in adult males (killing approximately 75 and 90% of the exposed flies, respectively). No increase in deaths was caused in larvae by the same concentrations. Only cytotoxic effects were observed in the test for dominant lethals. No conclusive genotoxic effects could be detected in any of the three germ cell assays. The coffee preparations were also tested for induction of mutation and mitotic recombination in somatic cells of the wing imaginal disc. Larvae trans-heterozygous for two recessive wing hair markers were fed high concentrations of the coffees for varying periods of time. Wings of surviving adult flies were analysed for mosaic spots. Twin spots exhibiting both mutant phenotypes are produced by mitotic recombination; single spots showing one or the other phenotype are the result of somatic mutation, such as gene mutation or deletion, or of mitotic recombination. Both coffees had weak effects on normal (repair-proficient) cells as well as on excision repair-defective cells in this assay. Additional experiments with pure caffeine and decaffeinated coffee show that these weak effects in somatic cells were most probably caused by the caffeine present in the two coffees. PMID- 3096847 TI - In vitro characterization of possible mechanisms underlying the selective in vivo accumulation of the PCB metabolite 4,4'-bis(methylsulphonyl)-2,2',5,5' tetrachlorobiphenyl in the lung. AB - In vivo, the polychlorinated biphenyl (PCB) metabolite 4,4'-bis(methylsulphonyl) 2,2',5,5'- tetrachlorobiphenyl--(MeSO2)2TCB--selectively accumulates in the Clara cells of the bronchiolar epithelium and in the secretory contents of the bronchiolar lumen. In vitro characterization of the interaction of tritiated (MeSO2)2TCB with the lung suggests that this selective accumulation is due to the presence of a secreted ([3H]MeSO2)2TCB-binding protein in the respiratory tract of rats, mice and man. The protein appears to be an almost globular, low molecular-weight acidic protein which binds ([3H]MeSO2)2TCB and certain other methylsulphonyl PCBs with high affinity. Because of the pathway outlined for accumulation, it is suggested that methylsulphonyl PCBs should be included in studies designed to elucidate the mechanism(s) of PCB-induced lung toxicity. PMID- 3096849 TI - Dietary influences on rat hepatic and intestinal DT-diaphorase activity. AB - DT-diaphorase (DTD) is a flavoprotein that catalyses the two-electron reduction of various redox dyes and quinones such as menadione and phylloquinone. It has been proposed that this enzyme may have a protective effect against cancer, as the two-electron reduction prevents the formation of toxic oxygen metabolites that may be generated as a result of the one-electron reduction catalysed by enzymes such as NADPH-cytochrome P-450 reductase. The effects of a purified diet supplemented with either 25% Brussels sprouts, phylloquinone (2.5 or 25 ppm) or 250 ppm indole-3-carbinol on hepatic and intestinal DTD activity in adult male Sprague-Dawley rats have been determined. One group was fed on the purified diet and dosed with 3-methylcholanthrene (20 mg/kg), 24 hr before being killed. Hepatic DTD activity was increased 3-fold in the indole-3-carbinol group, 4.4 fold in the sprouts-fed animals and 8.2-fold in the 3-methylcholanthrene-treated animals. Neither level of phylloquinone affected hepatic DTD activity. Intestinal DTD activity was increased 2.1-fold in the indole-3-carbinol group, 3.7-fold in the sprouts-fed animals and 4.3-fold in the 3-methylcholanthrene group. In animals given 25 ppm phylloquinone, intestinal enzyme activity was 60% of the control level, while no effect was noted in those given 2.5 ppm phylloquinone. Although increases in the activities of intestinal xenobiotic-metabolizing enzymes resulting from dietary influences are well documented, the increase in hepatic DTD activity seen in response to vegetable consumption has not been reported. The significance of these results in relation to the possible protective effects of dietary cruciferous vegetables against cancer is discussed. PMID- 3096850 TI - The role of carrageenan in complement activation. AB - A study has been made of the nature of the interaction between complement and carrageenan, which has been widely reported to inhibit haemolytic complement activity both in vivo and in vitro. Using modified haemolytic complement-fixation tests, the degree of complement consumption by various forms of carrageenan was measured in whole human and rat sera. The median effective concentrations of the carrageenans studied were found to lie in the range 3-300 micrograms/ml for the classical pathway and 500-7800 micrograms/ml for the alternative pathway and were unrelated to sulphate content, as determined by energy dispersive X-ray analysis. It was also found that carrageenan-coated sheep erythrocytes were lysed by complement. This activity was suppressed by ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, which inhibits the classical, but not the alternative pathway, providing conclusive evidence that carrageenan preferentially activates the classical pathway. This finding may help in elucidating the inflammatory reaction induced by carrageenan. PMID- 3096851 TI - Inactivation of metalloenzymes by food constituents. AB - Phenylethylaminoalanine (PEAA), derived from biogenic phenylethylamine and dehydroalanine, inhibited the enzymatic activity of the metalloenzyme, carboxypeptidase A (CPA). The inhibition was maximal at pH 7.0 in the pH range 7 8.5. The extent of inhibition increased with time of treatment and PEAA concentration. N-AcetylPEAA did not inhibit the enzyme, suggesting that the free alpha-NH2 group is required for inhibition. PEAA also inactivated the copper enzyme, polyphenol oxidase (tyrosinase). Comparative studies with three other inhibitors, lysinoalanine, ethylenediaminetetraacetic acid and sodium phytate, suggest that the potency of PEAA as an inhibitor of CPA is similar to that of sodium phytate. Of these four inhibitors and three thiol compounds also tested, PEAA was the least and cysteine the most effective against tyrosinase. The pattern of observations in these studies suggests differences in the mechanisms of action of the inhibitors studied. The formation of PEAA, lysinoalanine and sodium phytate in foods is of possible nutritional and toxicological significance. PMID- 3096852 TI - Effects of dietary Schizandra chinensis, brussels sprouts and Illicium verum extracts on carcinogen metabolism systems in mouse liver. AB - Ethanol extracts of Brussels sprouts (BRX), Schizandra chinensis (SZX) or Illicium verum (IVX) were added to a semi-purified basal diet and fed to adult male and female C57B1/6 mice for 14 and 10 days, respectively. Other groups received the unsupplemented basal diet or a mouse chow. Liver fractions were prepared from these mice to investigate the effects of the diets on the enzyme systems involved in benzo[a]pyrene (BP) and aflatoxin B1 (AFB1) metabolism. The effects of the microsomal or cytosolic liver fractions on the in vitro mutagenicity of BP and AFB1 and on the DNA binding of AFB1 were also studied. There were several apparently sex-related differences in the responses of the monooxygenase system components measured. In males, cytochrome P-450 levels were significantly increased only in the chow group, while significant increases in both 7-ethoxycoumarin O-deethylase (ECD) and aryl hydrocarbon hydroxylase (AHH) activities were seen only in the SZX group. In females, cytochrome P-450 levels were significantly increased in both the BRX and SZX groups, whereas AHH activity was significantly increased only in the chow and BRX groups and ECD activity was increased in the SZX and IVX groups. Microsomal epoxide hydratase (EH) was induced in males in the SZX and IVX groups and in females only in the SZX group, while cytosolic EH was significantly increased only in IVX males. Diet-induced changes in monooxygenase activities were found to be the best indicators of changes in microsome-mediated BP mutagenesis and AFB1 mutagenesis and binding to DNA in vitro, with a direct correlation between high AHH and/or ECD activities and the levels of mutagenic response to BP or AFB1 in the Ames assay and of DNA binding of AFB1. PMID- 3096853 TI - The pharmacokinetics of dichloromethane. I. Disposition in B6C3F1 mice following intravenous and oral administration. AB - The tissue distribution and metabolism of dichloromethane (DCM; CH2Cl2) was investigated in B6C3F1 mice following iv or oral administration. The route of exposure and the composition of the dosing solution were found to have a significant effect on the pharmacokinetics. Following single iv doses of 10 or 50 mg [14C]DCM/kg dose-dependent metabolism to 14CO2 and 14CO and rapid pulmonary clearance of unchanged 14CH2Cl2 characterized the elimination of DCM from the body. The highest concentrations of 14CH2Cl2 were found in the liver, lung and kidney, with more than 50% of the total radioactivity in these tissues represented by the parent compound. When DCM was administered orally in single gavage doses for 14 consecutive days at treatment levels of 50 mg/kg in water or 500 and 1000 mg/kg in corn oil, rapid absorption and elimination of DCM characterized the treatment in water while distinctly slower trends were found for the doses in corn oil. No observable pharmacokinetic or metabolic effect resulted from repeated oral dosing over the 2-wk treatment period. PMID- 3096854 TI - The pharmacokinetics of dichloromethane. II. Disposition in Fischer 344 rats following intravenous and oral administration. AB - The tissue distribution and metabolism of dichloromethane (DCM; CH2Cl2) was investigated in Fischer 344 rats following iv or oral administration. The route and level of exposure were found to have a significant effect on the disposition characteristics. A two-compartment model was used to describe the elimination of DCM from blood following single iv doses. The estimates of t1/2,beta were 11.9 and 23.5 min for doses of 10 and 50 mg/kg, respectively, and the disposition rate constants, beta were found to differ significantly at P less than 0.05. When DCM was administered orally (by gavage) in a daily dose of 50 or 200 mg/kg for 14 consecutive days, rapid absorption and distribution to the tissues characterized the disposition. Dose-dependent metabolism to 14CO2 and 14CO and rapid pulmonary clearance of unchanged 14CH2Cl2 were the dominant routes of elimination of DCM from the body following both iv and oral doses. No observable pharmacokinetic or metabolic effect resulted from repeated oral dosing. PMID- 3096855 TI - [Expression of functional human interleukin 2 receptor in mouse cells by using gene transfection]. AB - Interleukin 2(IL-2), a lymphokine that is produced by helper T cells, plays a key role in the proliferation of T lymphocytes by interacting with a specific cell surface receptor. Recent studies demonstrated that the IL-2 receptor exists in two forms having different affinities to the ligand and the growth signal seems to be delivered by IL-2 bound to the high affinity, but not the low affinity, receptor. In man, both forms of the IL-2 receptor can be recognized by a monoclonal antibody, anti-Tac. Using this antibody, a cDNA that encodes Tac antigen has been cloned from ATL-derived T cell line. Transfection of the cloned cDNA into mammalian non-T cells, however, resulted in the expression of only a non-functional, low affinity IL-2 receptor. This observation raised a question whether or not the cloned cDNA for Tac antigen actually encodes the functional, high affinity IL-2 receptor. In order to clarify this problem, Tac antigen cDNA was obtained from human PBL cDNA library. This cDNA was connected to RSV-LTR and was transfected into mouse thymoma derived T-cell line EL4, and L929 fibroblast. Then transformants that constitutively express Tac antigen were established. IL-2 binding assay demonstrated that EL4 transformants expressed high affinity as well as low affinity human IL-2 receptor. In contrast, L929 transformants expressed only a low affinity receptor. The growth of the EL4 transformants harboring the high affinity human IL-2 receptor was inhibited by virtue of the specific interaction of the receptor with human, but not mouse, recombinant IL-2. These results demonstrate: the cloned cDNA dose encode a functional IL-2 receptor, the affinity of the IL-2 receptor is variably modified by post-translational events and 3. IL-2/receptor interaction leads to the reversal of the cell growth in EL4 cells. The reconstitution system described here will be of great use in elucidating the mechanism of T cell growth. PMID- 3096856 TI - [The release of thromboxane A2 and prostacyclin due to vasoactive agents in hypercholesterolemic rabbits]. AB - The production of Thromboxane A2 (TXA2) and Prostacyclin (PGI2) in hypercholesterolemic state is considered to be different from that in normal state. The purpose of this study was to investigate the effect of vasoactive agents on the release of TXA2 and PGI2 in hypercholesterolemic rabbits (HCR). Hypercholesterolemia was induced in rabbits by feeding pellet food containing 1% cholesterol for 3 months. After blood sampling and blood pressure (BP) measurement in basal state, vasoactive agents such as ergonovine 2.0 mg/kg, norepinephrine 10.0 micrograms/kg and angiotensin II 0.5 micrograms/kg were administered intravenously to rabbits under the infusion of saline or vasodilators such as nitroglycerin 40 micrograms/kg/min and verapamil 20 micrograms/kg/min to suppress the increase in systolic BP (SBP) due to vasoactive agents. BP response was recorded, and blood was collected after BP returned to pre-injection level of vasoactive agents. TXA2 and PGI2 were measured as TXB2 and 6-keto-PGF1 alpha respectively by radioimmunoassay. Administration of the vasoactive agents increased the plasma level of both TXB2 and 6-keto-PGF1 alpha in normal control rabbits (NCR), whereas in HCR only TXB2 was markedly increased. The increase in TXB2 was suppressed by inhibiting the rise in SBP by vasodilators both in NCR and HCR. Neither TXB2 synthesis nor phospholipase A2 activity in platelets was affected by the vasoactive agents in vitro. These results suggest that the increase in SBP due to vasoactive agents affects on TXB2 release in vivo and we concluded that the release of TXB2 by BP response was greater in HCR than in NCR. PMID- 3096857 TI - Inhibitory effect of antimuscarinic cholinergic drug (atropine) on growth hormone (GH) secretion induced by GH-releasing factor. PMID- 3096858 TI - Regulation of prolactin secretion in canine pituitary-dependent hyperadrenocorticism. AB - In 15 dogs with pituitary-dependent hyperadrenocorticism (PDH) the basal prolactin concentrations (means of 6 determinations; range 2.8-24.7 micrograms/l) were significantly higher than those of 23 healthy control dogs (0.9-10.5 micrograms/l). In five dogs with hyperadrenocorticism due to adrenocortical tumour (ATH) the prolactin concentrations were also significantly elevated, but still significantly lower than the values of the dogs with PDH. The prolactin concentrations of the dogs with PDH responded supranormally to TRH-stimulation, whereas in the dogs with ATH the response was not significantly different from the results in the control dogs. Following bromocriptine administration the plasma prolactin concentrations of the dogs with PDH decreased considerably but remained higher than the values obtained in the control dogs and the dogs with ATH. It is concluded that PDH in the dog is associated with a disturbance in the regulation of prolactin secretion, that is not secondary to hypercortisolism per se. PMID- 3096859 TI - Effects of naloxone infusion on plasma levels of LH, FSH, and in addition TSH and prolactin in males, before and after oestrogen or anti-oestrogen treatment. AB - The inhibitory action of endogenous opioids on gonadotrophin release is now well documented. Since LHRH-producing neurons do not possess oestrogen-receptors, it is likely that some other compound mediates the negative feedback action of oestrogens on the gonadotrophin release in the male. To test the hypothesis that endogenous opioids are implicated in this negative feedback action in the human male, the opioid receptor antagonist naloxone (2 mg/h for 4 h) was infused into 7 normogonadotrophic oligozoospermic men before and after 6 weeks of treatment with the oestrogen-receptor antagonist tamoxifen (TAM) (10 mg twice daily) and 6 eugonadal transsexual males before and after 6 weeks of administration of ethinyloestradiol (EE) (10 micrograms three times a day). The effects of naloxone on TSH and prolactin (PRL) release were also studied. Naloxone administration resulted in a significant release of gonadotrophins, but not of TSH and PRL. Administration of oestrogen and anti-oestrogen did not significantly affect the response of gonadotrophins to naloxone infusion and no evidence of consistently antagonistic effects of oestrogen and anti-oestrogen on the naloxone-induced gonadotrophin release was obtained. This shows that endogenous opioids are probably not intermediary in the negative feedback control of oestrogens on gonadotrophin release in the human male. Surprisingly, in contrast to the eugonadal transsexual males, FSH levels in the oligozoospermic men did not respond to naloxone administration. As naloxone is thought to exert its action on gonadotrophin release via a disinhibition of endogenous LHRH release, this finding is unexpected. Exogenous LHRH administration leads to a normal response of FSH in normogonadotrophic oligozoospermic men. No plausible explanation for this finding can presently be offered. PMID- 3096860 TI - An inexpensive method for assessing pituitary response to luteinizing hormone releasing hormones: analysis of serum gonadotropins in pooled samples. AB - Sixty-two children, aged 2-18 years, suspected of an endocrine disorder were given one of several IM injections of the LHRH and the blood was drawn prior to and at 30, 60, 90, 120, 240 minutes after the injection. An aliquot of .2 ml of serum was taken from each post-LHRH specimen and pooled. The gonadotropins were measured in all the individual and pooled samples. A high correlation (r = .974, LH; r = .981, FSH) between the peak and the pooled sample suggests that the analysis of gonadotropins in a pooled sample gives information comparable to that obtained by the gonadotropin analysis in multiple serum samples. A formula to calculate the peak LH and FSH from the pooled specimen taken from only four post LHRH injections is: peak LH = 3.015 + 1.049 times the pooled LH; peak FSH = 3.153 + 1.072 times the pooled FSH value. The correlation coefficient between the observed and the calculated LH was .98; the same for the FSH was .987. I suggest that the pooled sample, due to it's integrated response, is a better reflection of the pituitary response to the LHRH. PMID- 3096861 TI - Trifluoperazine inhibits thyrotropin-releasing hormone-stimulated TSH secretion. AB - In previous work changes of the thyrotropic secretion after administration of some substances affecting the calcium content in the cytosol were demonstrated. The object of the present investigation was to assess the hormonal response to the administration of trifluoperazine, a psychopharmaceutical preparation, the main mechanism of its action being the inactivation of the cytosol receptor for the calcium signal - calmodulin. The poor utilization of intracellular calcium of the secretory cell is then the factor which inhibits secretion proper. The thyrotropic secretory reserve (delta TSH) was assessed in the same subjects before and after trifluoperazine administration by the TRH test as the difference of values at rest and TRH-stimulated TSH levels during the 20th, 30th, 40th and 60th minute following intravenous administration of 200 micrograms TRH. It was revealed that this calmodulin antagonist administered for one week in amounts of 6-12 mg per day by mouth significantly inhibits the secretory response of TSH to TRH in healthy subjects during the 20th and 40th min. (P less than 0.05). The reproducibility of the TRH test repeated in a group of subjects not treated with trifluoperazine, however, under equal conditions and after the same time intervals as in the experiment with trifluoperazine was very satisfactory and thus physiological inhibition caused by repeated TRH administration could be ruled out. The inhibition of the secretory TSH response to TRH can be therefore considered the consequence of the direct effect of trifluoperazine on the thyrotropic secretory mechanism. Trifluoperazine significantly reduced serum calcium levels and raised phosphate levels, while it did not affect the blood levels of magnesium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096862 TI - Effects of CS-514, a new inhibitor of HMG CoA reductase, on plasma lipids, lipoproteins and apoproteins in patients with primary hypercholesterolemia. PMID- 3096863 TI - Pharmacologic hypogonadotropism--an advantage for hMG-induced follicular maturation and succeeding fertilization. PMID- 3096864 TI - Zinc may play a role in the regulation of thyrotropin function. AB - We studied the in vitro and in vivo influence of physiologically relevant zinc concentrations on the thyrotropin function both at the pituitary and hypothalamic level. Zinc gluconate (Zn Glu) concentrations from 5 to 100 microM decreased basal TSH release from anterior pituitary gland in vitro, but did not affect TSH stimulated release by TRH, cAMP or high K+ concentrations. Zn Glu altered neither the basal nor stimulated production of TRH by hypothalami in vitro. In vivo brain third ventricle injection of Zn Glu decreased serum TSH 30-60 min after injection. The ability of physiological concentrations of zinc to influence TSH secretion both in vitro and in vivo suggest that this trace element might be involved in the regulation of thyrotropin function. PMID- 3096865 TI - The antidiabetic activity of aloes: preliminary clinical and experimental observations. AB - The dried sap of the aloe plant (aloes) is one of several traditional remedies used for diabetes in the Arabian peninsula. Its ability to lower the blood glucose was studied in 5 patients with non-insulin-dependent diabetes and in Swiss albino mice made diabetic using alloxan. During the ingestion of aloes, half a teaspoonful daily for 4-14 weeks, the fasting serum glucose level fell in every patient from a mean of 273 +/- 25 (SE) to 151 +/- 23 mg/dl (p less than 0.05) with no change in body weight. In normal mice, both glibenclamide (10 mg/kg twice daily) and aloes (500 mg/kg twice daily) induced hypoglycaemia after 5 days, 71 +/- 6.2 and 91 +/- 7.6 mg/dl, respectively, versus 130 +/- 7 mg/dl in control animals (p less than 0.01); only glibenclamide was effective after 3 days. In the diabetic mice, fasting plasma glucose was significantly reduced by glibenclamide and aloes after 3 days. Thereafter only aloes was effective and by day 7 the plasma glucose was 394 +/- 22.0 versus 646 +/- 35.9 mg/dl, in the controls and 726 +/- 30.9 mg/dl in the glibenclamide treated group (p less than 0.01). We conclude that aloes contains a hypoglycaemic agent which lowers the blood glucose by as yet unknown mechanisms. PMID- 3096866 TI - Effect of caerulein on pituitary response to TRH in humans. AB - The effect of caerulein (100 ng/kg/h X 1 h) on basal as well as on thyrotropin releasing hormone (TRH)-stimulated prolactin and thyroid-stimulating hormone (TSH) secretion was studied in healthy male volunteers. The peptide did not change the basal levels of prolactin and TSH. However, during the infusion of caerulein, prolactin response to TRH was significantly increased whereas the TSH response was decreased. These data, showing an action of caerulein (a frog peptide which mimics the biological actions of cholecystokinin) on prolactin and TSH release, suggest that cholecystokinin may be involved in the physiological control of human pituitary secretion. PMID- 3096867 TI - The preservation and loss of various non-haematopoietic antigens in human post mortem tissues as demonstrated by monoclonal antibody immunohistological staining. AB - Immunohistological methods using monoclonal antibodies have proved to be valuable in the differentiation between cells of various origins. We have previously shown most leucocyte differentiation antigens to be very resistant to post-mortem disintegration (Pallesen & Knudsen 1985). In the present study we have examined the preservation of several non-haematopoietic antigens in tissue samples of human skin, kidney, liver, pancreas, lung, thyroid gland, uterine tissue, female breast and brain from 30 autopsies performed at specific intervals after death. Frozen tissue sections were stained using monoclonal antibodies and an immunoperoxidase method. A total of 17 monoclonal antibodies against various intermediate filament proteins, epithelial antigens, various hormones and factor VIII related antigen were tested. We found surprisingly good preservation and staining of tissue antigens--even 3 d after death--in all organs except pancreas. It is concluded that many tissue antigens are fairly resistant to post-mortem disintegration and that immunohistology may be applied to diagnostic problems in human autopsy material. PMID- 3096868 TI - Simultaneous AL-type amyloid and light chain deposit disease in a liver biopsy: a case report. AB - A 57-year-old male caucasian presented with a peripheral neuropathy which had an autonomic component. Clinical examination revealed hepatomegaly and laboratory tests showed derangement of liver function tests and IgG lambda myeloma. Biopsy of the liver was performed. Histological examination revealed AL-type amyloid in the hepatic arteries and a perisinusoidal deposit of diastase resistant, periodic acid-Schiff positive material which did not react in the same way as the arterial deposit, giving no apple green birefringence when stained with Congo red. Immunohistochemistry showed the material to consist of lambda light chains. Electron microscopy confirmed that the material did not have the ultrastructural characteristics of amyloid. A diagnosis of light chain deposit disease concurrent with vascular AL-type amyloid was made. PMID- 3096869 TI - Systemic kappa light chain deposition and amyloidosis in multiple myeloma: novel morphological observations. AB - Light and transmission electron microscopic studies as well as immunohistochemical investigations were performed on a case of multiple myeloma in a 40-year-old female with systemic kappa light chain deposition. The latter took the form of extensive deposits in the liver, spleen and bone marrow. Amyloid was not found in these deposits, although it was present in the wall of branches of the portal vein. Conversely, amyloid but not light chain deposition was found in the tongue, synovial membrane from the knee and myocardium. The kidney was the only organ to show both amyloid and light chain deposits intimately associated with each other in and around tubules and collecting ducts. Ultrastructurally the light chain deposits were seen to be biphasic, having two granular components of different electron density. In the spleen and bone marrow, but not in the liver, the kappa light chain deposits were surrounded by multinucleated giant cells. This is the first report of light chain deposition disease associated with a foreign body type of giant cell reaction. The morphological variability of organ involvement suggests that the molecular structure and conformation of the deposited light chains are heterogeneous and may reflect a broad spectrum of metabolism of these deposits in various organs. PMID- 3096870 TI - Benign plexiform (multinodular) schwannoma: a rare tumour unassociated with neurofibromatosis. AB - In reviewing a large series of soft tissue tumours, seven cases of benign plexiform schwannoma have been retrieved. These were solitary lesions, not associated with von Recklinghausen's neurofibromatosis, which arose in the dermis or subcutaneous tissue, predominantly in young adults. None has recurred. While the schwannomatous nature of these rare lesions is readily appreciated, the frequent presence of nuclear pleomorphism and the plexiform growth pattern should not be regarded as having sinister prognostic significance. PMID- 3096872 TI - Multis set their own pace when entering LTC field. PMID- 3096871 TI - An overview of the Canadian health care experience. AB - Canada's universal health insurance system is designed to assure all Canadians access to free hospital and medical treatment. Each province has had considerable latitude in administering the system within its borders. To cope with rising costs, most provinces have adopted policies that limit physician income. Others have instituted fees for service users and have allowed physicians to bill patients for charges above the benefit schedule set by the province. These latter practices have been seen as eroding access to health care, and government funding for provinces that permit them was sharply curtailed by the Canada Health Act of 1984. The law is currently being challenged by the Canadian Medical Association because of the restrictions it places on physicians' freedom of practice. Although the Canadian system has created problems for physicians, the authors believe it provides a benefit no one wants to lose: accessible medical care for all. PMID- 3096873 TI - Hospitals travel some rough ground in LTC. PMID- 3096874 TI - LTC insurance: the race is on. PMID- 3096875 TI - Normomorphic sialidosis in two female adults with severe neurologic disease and without sialyl oligosacchariduria. AB - Two female patients of German origin, aged 38 and 21 years, with myoclonus epilepsy and cerebellar ataxia, but without dysmorphic signs and dementia, were found to excrete normal amounts of sialyl oligosaccharides in their urine. The younger patient showed cherry red spots in her ocular fundi. The older patient had a brother with an autopsy-proven neuronal storage disease compatible with sialidosis, and in her rectal biopsy lamellar inclusion bodies were detected. Enzyme assays in cultured fibroblasts of both patients revealed a profound but incomplete deficiency of oligosaccharide sialidase activity and normal beta galactosidase activity. Adult sialidosis was diagnosed in both patients. In their fibroblasts, moderate elevations of bound sialic acid could also be measured. The small residual sialidase activity, which in the older patient had a normal KM value, is considered responsible for the late onset and slow clinical course of the disease. It is concluded that in adult sialidosis the extraneural storage process can be difficult to demonstrate in terms of metabolite accumulation or excretion during the course of intraneuronal storage. PMID- 3096876 TI - 'Partnership in care'. PMID- 3096877 TI - Phenotypic and functional characterization of human Leu1 (CD5) B cells. AB - Leu1 B cells have been observed in high numbers in CLL patients, fetal spleen, and in bone marrow transplant recipients. We studied these cells in normal peripheral blood, spleen, and tonsil. They were phenotypically and functionally similar to conventional B cells. Leu1 B cells in the spleen and blood displayed a mature phenotype similar to the Leu1 B cells in the fetus, some expressing high levels of both sIgM and sIgD, and some expressing high levels of sIgD but little sIgM. Most Leu1 B cells in the tonsil also expressed high levels of both sIgM and sIgD, although some tonsil Leu1 B cells had high levels of sIgM but little sIgD. The significance of the Leu1 B cell is unknown, although it may be involved in the humoral immunoincompetence of the fetus, of CLL patients, and of transplant recipients. In our data there is no evidence to suggest that these cells are activated, immature, or capable of an immunoregulatory function. PMID- 3096878 TI - Development and physiology of Ly-1 B and its human homolog, Leu-1 B. PMID- 3096879 TI - The Ly-1 B cell lineage. PMID- 3096880 TI - Inhibition of IL-2 secretion and IL-2 receptor appearance of activated lymphocytes pretreated with hydroxylated sterols. AB - When murine BALB/c splenocytes are pretreated for 2 h with different concentrations of 25-hydroxycholesterol (25-HC) or 7 beta-hydroxycholesterol (7 HC), washed and stimulated either with irradiated C57BL/6 splenocytes or with Con A, IL-2 secretion is inhibited in a dose-dependent way as well as the subsequent cell proliferation. Using the same treatment and stimulation conditions, IL-2 receptor appearance on human T lymphocytes, as characterized by anti-Tac antibody binding, is also inhibited in a dose-dependent way. In contrast, the hydrophilic derivative of 7 beta-hydroxycholesterol, the 3.7 bishemisuccinate sodium salt (7 HC BHS), did not influence any of the 3 tested parameters. PMID- 3096881 TI - Cyclosporine inhibits the expression of receptors for interleukin 2 and transferrin on mitogen-activated human T lymphocytes. AB - The effect of cyclosporine A (CsA) on the mitogen-induced expression of Interleukin 2 receptor (IL2R) and transferrin receptor (TR) was monitored using receptor-specific monoclonal antibodies and flow cytometry. For all mitogens tested (PHA, Con A, OKT3, and Leu 4), expression of IL2R and TR, as well as DNA synthesis (3H-thymidine incorporation), were significantly reduced in the presence of CsA (0.5 microgram/ml). Titration experiments in the OKT3 system, the mitogen system most profoundly affected by CsA, revealed that CsA concentrations as low as 0.05 microgram/ml inhibited IL2R and TR expression and DNA synthesis, and that changes in DNA synthesis reflected changes in IL2R and TR expression. The addition of exogenous IL2 partially abrogated the CsA-mediated inhibition of all three activation parameters (IL2R, TR, DNA synthesis) in response to PHA, OKT3, and Leu 4. In contrast, exogenous IL2 did not reverse CsA-mediated reductions in Con A-stimulated activation parameters. These findings indicate that CsA inhibits mitogen-induced expression of IL2R and TR, and for some mitogen systems, this inhibition appears, at least in part, to be secondary to decreased IL2 production. PMID- 3096883 TI - Preliminary studies on comparative efficacy of Brucella abortus antigens in indirect immunofluorescence technique. PMID- 3096884 TI - Schistosomiasis of female genital tract. PMID- 3096882 TI - Genetic control of the production of anti-thyroid hormone antibodies in mice immunized with human thyroglobulin. AB - Various strains of mice with different H-2 and Igh-I allotypes were immunized with human thyroglobulin (HTg) and genetic control of the production of anti thyroid hormone antibodies was examined. Anti-HTg antisera obtained from different strains of mice were examined for the presence of anti-thyroid hormone antibodies. At least one Ir-gene which controls the production of anti-T4 antibodies by immunization with HTg was identified in the I-A subregion. The presence of Ir-genes outside the H-2 was also suspected. Concerning the production of anti-T3 antibodies, only three strains (B10.A, C3H.SW, BALB/cJ) were high responders and therefore we were unable to identify the Ir-gene for them. These results indicate the presence of Ir-gene which controls the immune response in mice against thyroid hormone and suggest that the anti-thyroid hormone antibodies observed in various thyroidal and non-thyroidal disorders could be anti-HTg antibodies. The significance of genetic control of the production of anti-thyroid hormone antibodies in mice immunized with HTg is discussed. PMID- 3096885 TI - Sarcocystis infection in man (a case report). PMID- 3096886 TI - Interactions of Bacteroides gingivalis with fibrinogen. AB - Results of previous studies from our laboratory have shown that a strain of Bacteroides intermedius isolated originally from a patient with acute necrotizing ulcerative gingivitis binds and degrades human fibrinogen (M.S. Lantz, L.M. Switalski, K.S. Kornman, and M. Hook, J. Bacteriol. 163:623-628, 1985). We report that strains of Bacteroides gingivalis, an organism implicated in the etiology of several forms of periodontitis, also bind and degrade fibrinogen. The binding is rapid, reversible, saturable, and specific. The number of fibrinogen-binding sites per cell varies from 500 to 1,500 in different batches of bacteria, and the dissociation constant for the complex is on the order of 10(-8) M. B. gingivalis possesses cell-associated fibrinogenolytic activity that is activated by dithiothreitol and blocked by thiol protease inhibitors. Interaction with fibrinogen may mediate colonization and establishment of these organisms in the periodontal microbiota. PMID- 3096887 TI - Interaction of complement with serum-sensitive and serum-resistant strains of Pseudomonas aeruginosa. AB - The interaction of complement with the following two strains of Pseudomonas aeruginosa was examined: 144M, a mucoid, serum-sensitive strain bearing short lipopolysaccharide O chains, and 144M-SR, a mucoid, serum-resistant strain bearing long lipopolysaccharide O chains isolated by repeated passage of 144M in increasing concentrations of pooled normal human serum (PNHS). While significant killing of 144M occurred in 5 to 40% PNHS, no killing of 144M-SR was observed. Both strains activated complement, especially 144M-SR which consumed 88.7, 96.4, and 100% of the available complement 3 (C3), C5, and C9, respectively, in 10% PNHS during a 60-min incubation at 37 degrees C. Although it activated more C3 than did 144M (54.9% consumption), 144M-SR bound only half as much C3 as 144M. Similarly, although 144M-SR activated more C9 than did 144M (50.0% consumption in 60 min), there was considerably less C9 attached to 144M-SR (2,990 molecules of C9 per bacterium) than to 144M (13,700 molecules per bacterium) after 60 min of incubation. Furthermore, only 162 molecules of the C9 bound to 144M-SR remained bound after treatment with 0.1% trypsin, while 5,692 molecules of the C9 bound to 144M remained bound under similar conditions. These results show that the serum resistance of 144M-SR does not represent a failure to activate complement efficiently, but instead reflects failure of the assembled terminal complement complex C5b-9 to insert stably into the outer membrane of this strain. PMID- 3096888 TI - Human immune response to iron-repressible outer membrane proteins of Neisseria meningitidis. AB - Neisseria meningitidis grown under iron-limiting conditions in vitro expresses additional iron-repressible outer membrane proteins (FeRPs). To see which FeRPs were expressed and immunogenic in human infection, we examined purified membranes from four meningococcal disease isolates with Western blotting of patient sera. Convalescent serum from each patient contained immunoglobulin G (IgG) and IgM antibodies against the homologous 70-kilodalton (kDa) FeRP and IgG antibody to the homologous 94-kDa FeRPs. Three other immunoreactive FeRPs were identified in two or more strains. Neither acute-phase sera nor pooled normal human sera contained appreciable levels of these antibodies. Antigenic cross-reactivity among FeRPs was suggested by the observation that the convalescent sera of two patients contained IgG antibodies reactive with the 70- and 94-kDa FeRPs and IgM antibodies reactive with the 70-kDa FeRPs from all four strains. Additionally, rabbit antiserum against the 70-kDa FeRP from one of these disease isolates contained IgG and IgM antibodies that reacted in Western blots with the 70-kDa FeRPs in all four strains. These results demonstrate that meningococcal FeRPs are expressed and immunogenic in vivo and that certain of these proteins are immunologically cross-reactive. PMID- 3096889 TI - Eosinophil chemotactic lymphokine produced by egg-associated granulomas in murine schistosomiasis japonicum. AB - Eosinophil chemotactic factor (ECF) was detected in the culture supernatant of isolated intact egg granulomas from the livers of Schistosoma japonicum-infected mice. This factor had an apparent molecular weight of 15,000 by high-pressure liquid chromatography with an SW3000 column and bound to concanavalin A-Sepharose 4B. When cells obtained by enzymatic digestion of isolated granulomas were cultured under the presence of soluble egg antigen of S. japonicum or concanavalin A, ECF was also detected in the conditioned medium. The physicochemical nature of the ECF produced by concanavalin A-stimulated granuloma cells was similar to that produced by isolated intact granulomas. The ECF producing activity of the cells was abolished by pretreatment with anti-Thy-1.2 or anti-Lyt-1.2 monoclonal antibody and complement but not by anti-Lyt-2.2 antibody. Furthermore, nylon wool-passed, T-enriched granuloma cells required collaboration of syngeneic macrophages to produce ECF. These results suggest that Lyt-1-positive T cells in the granuloma could, in collaboration with macrophages, produce ECF and thereby attract eosinophils to this lesion. PMID- 3096890 TI - Influence of endotoxin-protein in immunoglobulin G isotype responses of mice to Brucella abortus lipopolysaccharide. AB - Brucella abortus endotoxin preparations, containing approximately 5 to 6% protein, induce strong immune and adjuvant immunoglobulin G (IgG) responses as compared with Escherichia coli endotoxin preparations, with equivalent amounts of protein, which induce responses in which IgM antibody predominates. Using an enzyme-linked immunoassay with isotype-specific conjugates, we found that antibody of all four subclasses of IgG were evoked during the course of the immune responses of C3H/HeAu mice to B. abortus endotoxin. Secondary responses of endotoxin-hyporesponsive C3H/HeJ mice were similar to those seen in C3H/HeAu mice, although lower levels of antibody were produced during their primary responses. The primary responses of BALB/c athymic mice consisted almost entirely of IgG3, and IgG1 appeared following a second injection. The effects of lipopolysaccharide (LPS)-associated protein on the immunogenic properties of B. abortus endotoxin were examined by comparing responses to endotoxin with those to a purified B. abortus LPS containing less than 1% protein. The endotoxin evoked strong primary and secondary responses in which antibody directed to LPS determinants consisted mainly of IgG3 and those to the protein determinants were largely IgG1 antibody. Primary and secondary responses to purified LPS consisted mainly of IgG3 antibody. The potential mechanism of the contribution of protein to the immunogenic properties of the endotoxin as well as possible immune mechanisms involved in these responses are discussed. PMID- 3096891 TI - Synthesis and secretion of interferon by murine fibroblasts in response to intracellular Listeria monocytogenes. AB - Listeria monocytogenes, a gram-positive facultative intracellular bacterium, was shown to be capable of infecting and proliferating in murine embryo fibroblasts. During exponential proliferation, the doubling time of the bacterium was determined to be 2.5 h intracellularly, compared with 25 min extracellularly. Progressive intracellular growth of listeriae ultimately resulted in the destruction of initially infected cells and the spread of infection to neighboring cells. Listeria infection induced fibroblasts to synthesize considerable quantities of an acid-stable interferon that proved to be antigenically indistinguishable from both polyinosinic-polycytidylic acid-induced and virus-induced interferon. PMID- 3096892 TI - Mycobacterium leprae-specific Lyt-2+ T lymphocytes with cytolytic activity. AB - Mice were immunized intradermally with 10(7) irradiated Mycobacterium leprae organisms, and draining lymph nodes were collected after 4 weeks. Lymph node cells were restimulated in vitro with soluble M. leprae antigen and accessory cells. The resulting T-cell line was propagated in vitro in the presence of M. leprae antigen, accessory cells, and interleukin-2-containing supernatants from concanavalin A-stimulated rat spleen cells. Long-term cultured T cells were Thy 1+ L3T4- Lyt-2+ as revealed by analysis with the fluorescence-activated cell sorter. From this line, T-cell clones with the same phenotype were established. The T-cell clone A4 failed to secret interleukin-2 after stimulation with antigen and accessory cells, and its growth depended on exogeneous interleukin-2. A4 T cells produced gamma interferon in an antigen-specific, H-2-restricted, and interleukin-2-dependent way. Importantly, this T-cell clone was capable of lysing bone marrow macrophages presenting M. leprae antigen. Other T-cell clones as well as native Lyt-2+ T cells from M. leprae-immunized mice were also capable of lysing bone marrow macrophages expressing M. leprae antigens. These findings suggest that specific Lyt-2+ T cells participate in the immune response to M. leprae. It is postulated that cytolysis of M. leprae-infected macrophages or Schwann cells contributes to protection against and pathogenesis of leprosy. PMID- 3096894 TI - Surface-exposed antigenic cleavage fragments of Neisseria gonorrhoeae proteins 1A and IB. AB - Whole bacteria, isolated outer membranes, and purified protein I (PI) from one transparent (O-) and two different opaque (O+) phenotype gonococcal strains (serogroups I, II, and III; PI serotypes 1, 5, and 9b) were each treated with tolylsulfonyl phenylalanyl chloromethyl ketone-trypsin, alpha-chymotrypsin, and proteinase K. Protein IA (PIA) of strain 7122 (O-, serotype 1, serogroup I) was resistant to proteolysis by tolysulfonyl phenylalanyl chloromethyl ketone-trypsin and alpha-chymotrypsin and only slightly affected by proteinase K, as long as it was associated with intact bacteria or isolated outer membranes. Purified PIA however was cleaved by these enzymes, resulting in two to five fragments. In contrast, all preparations of strains 5766 opaque phenotype (O+, serotype 7, serogroup II) and 1955 (O+, serotype 9b, serogroup III) were accessible to proteolysis, resulting in cleavage fragments of PIB compatible to those described previously by O. Barrera and J. Swanson (Infect. Immun. 44:565-568, 1984), M. S. Blake et al. (Infect. Immun. 33:212-222, 1981), and Blake (in G. K. Schoolnik, ed., The Pathogenic Neisseriae, 1985). Our data indicated that the purified PIB fraction was more accessible to proteases than the PIBs of whole bacteria or outer membranes. The fragmentation pattern of PIA cleavage products were quite different from PIB fragments, consistent with the different structure of these two groups of PI molecules. Time-dependent cleavage experiments with proteases, i.e., alpha-chymotrypsin, indicated that PIA was subsequently cleaved into smaller fragments. Highly reactive monoclonal antibodies, each specific for a surface-exposed epitope of PIA of strain 7122 or PIB of strains 5766 and 1955, as assessed by coagglutination, Western blot, and immunofluorescence, were reacted with PIA and PIB cleavage fragments in Western blot experiments. All cleavage fragments of the purified PIA and PIB preparations with molecular weights of greater than or equal to 14,200 showed immune reaction in Western blotting, whereas whole cell and outer membrane PIB fragments were less reactive with the specific monoclonal antibodies. PMID- 3096893 TI - Anti-L3T4 antibody treatment suppresses hepatic granuloma formation and abrogates antigen-induced interleukin-2 production in Schistosoma mansoni infection. AB - In murine schistosomiasis mansoni, granulomatous inflammation is an immune response that involves egg antigen presentation to T cells in the context of class II major histocompatibility complex determinants and subsequent inflammatory lymphokine production by delayed-hypersensitivity (TDH) lymphocytes. In the present study, monoclonal antibodies directed against L3T4, I-A, and Lyt-2 molecules were injected intraperitoneally into S. mansoni-infected mice to study the role of these membrane antigens in the process of granuloma formation. A dramatic suppression of the hepatic granuloma size and antigen-induced interleukin-2 (IL-2) production by spleen cells was seen in mice that received anti-L3T4 monoclonal antibody treatment. The total number of cells, especially the L3T4+ T cells, was greatly diminished in the spleens. Furthermore, histopathological study of the granulomas in stained liver sections demonstrated the paucity of eosinophils and macrophages, absence of epithelioid cells and multinucleated giant cells, and minimal collagen deposition within the lesions. Damaged hepatocytes were also seen surrounding these ill-formed granulomas. In contrast, anti-I-A monoclonal antibody treatment partially suppressed IL-2 production, although granuloma size and cellular composition remained the same. Mice that received anti-Lyt-2 monoclonal antibody did not show any changes in either IL-2 production or hepatic granulomatous inflammation. The data presented in this paper indicate a crucial role for L3T4 molecules present on a subset of class II major histocompatibility complex-restricted TDH cells in IL-2 production and the generation of the granulomatous response. PMID- 3096895 TI - Influence of mouse genotype on passive systemic anaphylaxis by immune complexes. AB - The influence of mouse genotype on passive systemic anaphylaxis (PSA) by immune complexes was studied. PSA was induced by using Brucella abortus endotoxin as the antigen and rabbit anti-Brucella endotoxin antisera. Experiments using syngeneic mice as well as mice congenic for H-2 showed that the H-2 haplotype influenced the sensitivity of mice to PSA. Among the H-2 haplotypes studied, H-2b was the most sensitive, followed by H-2k and H-2d. Experiments using passive transfer of serum as well as the complement inhibitors suramin and flufenamic acid indicated that variations in complement levels under control of H-2 may be responsible for the effects described. Cyproheptadine, a blocker of serotonin and histamine receptors, and imidazol-alpha-ketoglutarate, an inhibitor of thromboxane synthesis, inhibited PSA, indicating that platelet aggregation, possibly mediated by activated components of the complement cascade, is an important feature in the development of PSA reactions in this system. Differences between strains for protection by cyproheptadine and for the effect of complement inhibitors indicated a role of early components of the classical pathway in this model. PMID- 3096896 TI - Cross-reactions of lipopolysaccharides of Pseudomonas aeruginosa in antipneumococcal and other antisera. AB - Lipopolysaccharides of the seven Fisher immunotypes of Pseudomonas aeruginosa gave cross-precipitation in many antipneumococcal sera. The reaction of Pseudomonas type IV in type 25 antipneumococcal serum was immediate and heavy: 93 micrograms of antibody nitrogen per ml. Correlations are described, mainly between the structures of the O-chains of the immunotypes and their specificities as shown by the cross-reactions. PMID- 3096897 TI - Efficacy of a combined treatment with plasma exchange and cytostatics in macroglobulinemia. AB - Monthly plasma exchange (PE) sessions have been carried out in 3 patients with advanced Waldenstrom macroglobulinemia, in order to reduce electrophoretic M band under 2g/100 ml. When PE was combined to low doses of cytostatics (n = 18), 3 procedures per session were required to obtain a mean 57.4 +/- 12.3% IgM reduction, from 4.2 +/- 1.2 to 1.7 +/- 0.5 g/100 ml. A mean 61.5 +/- 13.1% IgM reduction, from 5.5 +/- 1.3 to 2.1 +/- 1 g/100 ml, was obtained in 64 procedures carried out as the only therapy in 12 sessions, with 5.3 procedures requirement per monthly session. IgM percent reduction 24 hours after PE was greater with combined treatment (45 +/- 9.7 vs. 28.9 +/- 15.4%; p = 0.001). The advantage of a combined treatment is therefore either a lowered PE requirement or a tapered maintenance cytostatic dosage. PMID- 3096898 TI - Enzyme-based hemoperfusion and blood treatment. AB - Enzyme-based artificial organs are being developed as metabolic assist devices. These are required when normal metabolism is impaired, or when the body is overloaded by undesired metabolites or toxins. The implementations of this approach for treating a genetic disease, and for metabolic support in liver failure are envisaged. The kinetic aspects and mass transfer characteristics of bioreactors for these systems are considered in detail. PMID- 3096899 TI - Prophylactic treatment of childhood asthma. AB - The prophylaxis of childhood asthma is discussed under the headings of prevention by the pregnant mother in avoiding hypersensitizing foods and the adherence to breast feeding, immunotherapy of the child and chemoprophylaxis by sodium cromoglycate or ketotifen fumarate. The results of a multicentre study of the latter drug are described. Ketotifen caused a reduction of symptoms and acute asthmatic episodes, and has the advantage of a twice daily oral dosage. PMID- 3096900 TI - Recovery of age-related decline of thymic endocrine activity and PHA response by lysin-arginine combination. AB - The frequent association of malnutrition, infectious diseases and aging has stressed the role played by some nutrients on the immune efficiency and by nutrient supplementation on the age-dependent immunological decline. In the present paper there are reported evidences that oral administration of two amino acids--lysine and arginine--recovers, in old Balb/c mice, the mitogen responsiveness, the expression of T-cell markers and the production of thymic serum factor (thymuline). The effect of the amino acids or of their combination, as present in a commercially available form (Neoiodarsolo), seems to consist mainly of the reactivation of the endocrine activity of the thymus. Similar reactivation is achieved also in old humans. These data suggest that the age dependent decline of thymic hormonal activity is not an intrinsic and irreversible event and that some nutritional intervention, such as amino acid treatment, likely through the stimulation of neuroendocrine network, may reactivate the endogenous production of thymic hormones. PMID- 3096901 TI - Selective effects of human cord serum on distinct events of the lectin-induced activation and proliferation of thymic T-cells. AB - The results of this study demonstrate that human cord serum, but not adult serum, contains a factor(s) which without being by itself mitogenic for unstimulated resting cells, enhances the PHA- and ConA-induced proliferation of rat thymocytes. Dissection of the effects of HCS on the distinct events involved during lectin-induced activation and growth of thymic T cells, revealed the basic mechanisms by which the stimulatory factor(s) exerts its action. HCS does not affect the IL-2-dependent proliferation of ConA-blasts derived from thymocytes. Furthermore, it does not act via macrophages but rather directly on thymic T cells by increasing their capacity to proliferate in response to the activating signals delivered by lectins in conjunction with IL1. Thus, HCS enhances the lectin-induced expression of IL2-receptors as evidenced by both increased responsiveness to IL2 and increased capacity to absorb IL2 of HCS-treated thymocytes. On the other side, HCS also enhances the lectin-induced production of IL2 by thymocytes. PMID- 3096903 TI - Significance of nosocomial infection rates in the era of DRGs. PMID- 3096902 TI - Schistosoma mansoni: the cutaneous response to cercarial challenge in naive guinea pigs and guinea pigs vaccinated with highly irradiated cercariae. PMID- 3096904 TI - Computed tomography of the orbit. PMID- 3096905 TI - Long-term care--an impending crisis. PMID- 3096906 TI - A study using an isotope probe comparing immunoassay with serology in detection of brucella abortus antibody. PMID- 3096907 TI - Serological and biochemical genetic markers in congenital cleft lip and cleft palate anomalies. AB - Serological and biochemical genetic markers in 76 patients with cleft lip with or without cleft palate [CL(P)] and 24 patients with isolated cleft palate (CP) were studied and compared with healthy control subjects. Blood group A phenotype and homozygous plasma haptoglobin (2-2) were found associated with CL(P). The findings suggest that the individuals possessing these markers are more likely to develop congenital CL(P). PMID- 3096908 TI - Neurofibromatosis in pregnancy. Four case reports and review of the literature. AB - Neurofibromatosis (Recklinghausen's disease) is an autosomal dominant disorder that affects multiple organ systems. The disease usually manifests itself during puberty although it occasionally occurs during infancy and childhood. Pregnancy seems to exacerbate the condition. Four cases of neurofibromatosis during pregnancy are presented. Three of the patients had uneventful pregnancies and deliveries, and the fourth had severe thrombocytopenia. This complication has not previously been reported in association with neurofibromatosis in pregnancy. By close supervision of pregnant patients with neurofibromatosis, most complications can be avoided. PMID- 3096909 TI - Cost analysis for case-mix complexity of a medical ward in a general city hospital in Israel. PMID- 3096910 TI - Noradrenergic mediation of adrenocortical responses following cortical stimulation in the rat. PMID- 3096911 TI - Treatment of intractable cluster. PMID- 3096912 TI - An inexpensive and multipurpose calibration phantom for in-vivo measurements of internal contaminants. PMID- 3096913 TI - Hemoglobin Linkoping [beta 36 (C2) Pro----Thr] in a large Finnish family from Astoria, Oregon, USA. AB - Eleven members of a large Finnish family from Astoria, Oregon were studied because of an erythrocytosis. No abnormality was detected by the usual hemoglobin electrophoretic tests, but an abnormal variant was separated by reverse phase HPLC. All of the affected individuals have an increased oxygen affinity with a P50 for whole blood at 37 degrees C averaging 18 torr. Fifty percent of their hemoglobin was found to have a threonyl residue in place of the normal prolyl residue at position 36 (C2) of the beta globin chain. This abnormality is identical to Hb Linkoping which was recently reported in a Finnish man living in Sweden. PMID- 3096915 TI - Aminomethyl coumarin acetic acid: a new fluorescent labelling agent for proteins. AB - A new fluorescent protein labelling agent, 7-amino-4-methyl coumarin-3-acetic acid (AMCA), emits in the blue region (440-460 nm) on activation with UV light (350 nm). The active reagent is the N-hydroxysuccinimide ester which reacts with lysine residues under mild conditions to form photostable amide links. The Stokes shift of 100 nm compared to 30 nm for Fluorescein isothiocyanate (FITC) allows easy filter discrimination of exciting and emitting radiation. The agent has been demonstrated in use for fluorohistochemical examination of human kidney glomeruli, using the sandwich technique and compared with the same procedure using FITC-labelled antibodies. The good quantum yield coupled with convenient emission lines in the mercury spectrum allows photographic exposure time of fluorescent labelled sections to be reduced to a quarter of that required for a corresponding FITC conjugate. AMCA-immunoglobulin conjugates were not susceptible to photobleaching and have a storage life at -20 degrees C of more than two years. PMID- 3096914 TI - Enzyme histochemistry of human melanomas and pigmented naevi with special reference to alpha-D-mannosidase activity. AB - A histochemical study of alpha-D-mannosidase revealed that normal human melanocytes (resting state, activated, lentigo simplex) exhibit either no or just detectable activity, as do melanocytes in the initial phase of lentigo maligna. Junctional, or occasionally zone A naevocytes displayed a very low enzyme activity. On the other hand, melanocytes in the initial stage of neoplastic transformation (dysplastic naevi, advanced stage of lentigo maligna) and also melanoma cells in disorders of low malignant potential (initial naevogenic melanoma, superficial spreading melanoma) displayed a high activity uniformly throughout the cell population. In the malignant forms (nodular melanoma, recurrences, metastases), the enzyme activity was remarkably heterogeneous, suggesting a breakdown of uniformity during malignant transformation. The significance of alpha-mannosidase activity induction in the course of melanocyte neoplastic transformation is not clear at present. The results of biochemical assays suggest that the lysosomal isoenzyme is mainly responsible. Other lysosomal enzymes, and dehydrogenases studied concomitantly, did not display any comparable phenomena of induction or similar behaviour. However, the results of a comparison of alpha-mannosidase with the melanocyte reference enzyme tyrosinase suggested activity patterns in the enzyme pair which may provide a better insight into the biochemical differentiation of human melanocytes in neoplastic disorders. The possible relationship of alpha-mannosidase to melanogenesis is also discussed. PMID- 3096917 TI - The body burden of chelatable lead, zinc and copper: a kinetic study in metal workers. PMID- 3096916 TI - Tissue-type plasminogen activator in rat adrenal medulla. AB - Rat adrenal glands were stained immunocytochemically using antibodies against plasminogen activators of the tissue-type (t-PA) and urokinase-type (u-PA). A subpopulation of the cells in the adrenal medulla showed intense cytoplasmic t-PA immunoreactivity, while no u-PA immunoreactivity was detected in any adrenal cells. Fluorescence microscopy of adjacent sections demonstrated that the cells stained for t-PA contained noradrenaline. Analysis with a histochemical fibrin slide technique demonstrated a plasminogen-dependent fibrinolysis in the adrenal medulla. SDS-PAGE of adrenal gland extracts followed by zymography established the molecular weight of this plasminogen activator to be similar to that of rat t PA. In addition SDS-PAGE followed by immunoblotting with anti-t-PA IgG of adrenal gland extracts revealed one band with an electrophoretic mobility indistinguishable from that found in the zymography. When tissue-sections and immunoblots were incubated with antibodies absorbed with highly purified t-PA no staining was found. In view of the previous finding of t-PA in growth hormone containing cells of the pituitary gland, these findings substantiate that t-PA can be found in the intact normal organism outside endothelial cells, and further point to t-PA having a function in endocrine cells. PMID- 3096918 TI - An in vitro and in vivo screening system for new hypoxic cell radiosensitizers using EMT6 cells. AB - An experimental tumor system consisting of single cells, spheroids, and solid tumors was developed using the EMT6/KU cell-line for evaluation of new hypoxic cell sensitizers. This paper describes the radiation dose-survival curves of the system and the effects of four sensitizers [misonidazole, Ro 03-8799, KB-11 (a sulfonyltetrazole derivative), and DNIE (a dinitroimidazole derivative)] in this system. Dose-survival curves of the spheroids varied significantly depending on the irradiation conditions, but it was found that the spheroids could model the solid tumors when they were irradiated in flat-bottomed flasks. These spheroids and solid tumors contained substantial fractions of hypoxic cells, and hence were suitable for testing hypoxic cell sensitizers. Misonidazole at a concentration of 1 mM or 1 mmol/kg showed a constant enhancement ratio (ER) of 1.55 in all of the systems. The ERs of the other three compounds for single cells, spheroids, and solid tumors were 2.1, 1.9, and 1.65, respectively, for Ro 03-8799 (1 mM or 1 mmol/kg); 2.6, 1.6, and 1.0, respectively, for KB-11 (0.5mM or 0.5 mmol/kg); 1.8, 1.2, and 1.1, respectively, for DNIE (0.5mM or 0.5 mmol/kg). These results indicated that the ER for spheroids is closer to the ER for solid tumors than is the ER for single cells in most cases. It was also suggested that an efficient sensitizer in vivo shows little or no difference between its ER for single cells and that for spheroids. PMID- 3096919 TI - Antimetastatic effect of biological response modifiers in the "double grafted tumor system". AB - The antimetastatic effect of biological response modifiers (BRM) in a new experimental mouse model was studied. Intratumoral administration of BRMs (PSK, OK-432, interferon alpha A/D) strongly inhibited the growth of Meth-A solid tumors in male BALB/c mice and led to a complete regression of tumors and resistance to reinoculated tumors. Subsequently, the antimetastatic effect of BRMs was examined in the "double grafted tumor system," in which mice first received simultaneous intradermal inoculations of Meth-A in the right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with BRMs in the right tumor on day 3. PSK and interferon (IFN) significantly inhibited the growth of the left (non-treated) tumor. This finding suggests that intratumoral BRM immunotherapy in one region has an effect on tumor growth in another region. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of BRMs and had rejected reinoculated tumors. One hour after intravenous injection of cyclophosphamide (2 mg/mouse), immunized spleen cells (2 X 10(7) cells/mouse) were injected into the Meth-A tumor on day 3. Adoptive transfers of PSK and IFN immunized spleen cells caused the complete regression of Meth-A tumors. These results suggest that the intratumoral administration of BRMs might induce cytotoxic cells in the left non-treated tumor of the "double grafted tumor system" and bring about the regression of metastatic tumors. PMID- 3096920 TI - Antitumor activity of new semisynthetic saframycin derivatives. AB - Saframycins Yd-1 and Y3, which have an amino functional group in the side chain, were recently obtained by a directed biosynthesis. Twenty-eight side chain modified chemical derivatives were prepared from these saframycins, and their in vitro and in vivo antitumor activities were studied. Among these new derivatives, three saframycins, namely, two N-acyl derivatives, pivaloyl- and n caproylsaframycin Y3, and one water-soluble type, saframycin Yd-1.HCl, were found to show marked antitumor activity against L1210 mouse leukemia cells. Further studies of these saframycin derivatives using B16-F10 melanoma and Lewis lung carcinoma indicated that all three saframycins are also active against B16-F10 melanoma; saframycin Yd-1.HCl showed the greatest prolongation of survival time. Marked inhibition of spontaneous metastasis of Lewis lung carcinoma was observed in mice treated with these new derivatives. Structure-activity relationships among these semisynthetic saframycins are discussed. PMID- 3096921 TI - Some contributions to science by the Radiation Effects Research Foundation (Formerly the Atomic Bomb Casualty Commission). PMID- 3096922 TI - Expression of epidermal growth factor receptor gene in cultured human lung cancer cells. AB - The expression and organization of epidermal growth factor (EGF) receptor gene in cultured human lung cancer cell lines (5 adenocarcinomas, 3 squamous cell carcinomas, 2 small cell carcinomas and 1 large cell carcinoma) have been studied. Two (PC-8 and PC-9) of the adenocarcinomas overproduced EGF receptor mRNA and protein, and exhibited gene amplification, the magnitude of which was comparable to that of A431 cells. Six cell lines (3 adenocarcinomas, 2 squamous cell carcinomas and 1 small cell carcinoma) expressed EGF receptor gene and its product to a significant level without gene amplification, and the other three cell lines were found to be negative as regards expression. PMID- 3096923 TI - Effects of physical restraint on leukemogenesis by Friend virus. AB - The effects of physical restraint on the development of Friend erythroleukemia in ddY mice were examined. Restraint was applied by immobilizing the mice in wire cages. In both sexes there was a reduction in the weight of the whole body, thymus and spleen, though the food intake was not reduced. The incidence of leukemia was reduced in the males, but not in the females, while the latent period was prolonged in both sexes. This sex dependency is characteristic of the stress response. PMID- 3096924 TI - Studies on 6 alpha-substituted penicillins. II. Synthesis and structure-activity relationships of 6 beta-(2-aryl-2-sulfoacetamido)-6 alpha-methoxy penicillanic acids. AB - The synthesis and antibacterial activity of 6 alpha-methoxysulbenicillin analogues (2) are described. Structure-activity studies of these derivatives bearing hydrophilic substituents in the phenyl ring led to the identification of disodium 6 beta-[D-2-(3,4-dihydroxyphenyl)-2-sulfoacetamido]-6 alpha methoxypenicillanate (2m) as a compound with potent activity against Pseudomonas aeruginosa including beta-lactamase producing strains. Additional substitution of 2m gave derivatives 2p, 2q, 2r, with a further improvement in activity against Gram-negative bacteria. PMID- 3096926 TI - Synthesis and antibacterial activity of a novel biphenyl-ureido penicillin. PMID- 3096925 TI - Structure-activity relationships of some 6 alpha-formamido penicillins. PMID- 3096927 TI - Negative control for the expression of streptomycin resistance gene from streptomycin-producing Streptomyces griseus. PMID- 3096928 TI - Use of carbon-13 in biosynthetic studies: origin of the malonyl coenzyme A incorporated into tetracycline by Streptomyces aureofaciens. AB - The proton noise decoupled 13C nuclear magnetic resonance spectrum of tetracycline hydrochloride prepared from Streptomyces aureofaciens cultures supplemented with [1-13C]acetate and [2-13C]acetate showed enrichment of nine alternating ring carbons. In addition, a small enrichment of the carboxamide carbon by [1-13C]acetate was observed. The labelling patterns clearly demonstrated the polyketide origin of the tetracyclic nucleus. The 13C nuclear magnetic resonance spectrum of tetracycline hydrochloride derived from [1,2 13C]acetate showed all 18 ring carbons as doublets with coupling constants appropriate for the incorporation of nine intact two-carbon precursors, confirming that head-to-tail condensation of C2 units had occurred. Absence of bond scission within the C2 units and a low level of uncoupled 13C in the carboxamide substituent indicated that when the organism is supplemented with acetate, malonyl coenzyme A used for tetracycline biosynthesis is formed by direct carboxylation of acetyl coenzyme A. PMID- 3096929 TI - Studies on pristinamycin synergism in Staphylococcus aureus. AB - Binding experiments were performed with both components of the pristinamycin complex (pristinamycin IA (PIA) and pristinamycin IIA (PIIA] using ribosomes from sensitive and resistant Staphylococcus aureus. Fluorescence polarization was used to measure PIA binding. The results obtained show a direct correlation between inhibition, synergy and the enhancement of the affinity of PIA for its receptor in the presence of PIIA. The uptake of PIA by intact cells seems to be directly correlated with affinity between PIA and ribosomes, a phenomenon which is probably shared with the macrolide antibiotics. PMID- 3096930 TI - Irreversible binding of pristinamycin IIA (streptogramin A) to ribosomes explains its "lasting damage" effect. AB - In vitro and in vivo studies are presented to test the hypothesis that the synergistic action of the pristinamycins is not due to a catalytic effect of pristinamycin IIA (PIIA) on the bacterial ribosome. We demonstrate that there is a proportionality between the quantity of PIIA bound on the ribosome and pristinamycin IA (PIA) retained by it. Moreover in vitro and in vivo experiments correlated to biological effects (growth and protein synthesis) demonstrate that pristinamycin IIA is tightly bound on 70S ribosome, which satisfactory explains the so called "lasting damage effect". PMID- 3096931 TI - Bactericidal activity of alkaline glutaraldehyde solution against a number of atypical mycobacterial species. AB - The mycobactericidal activity of 2% alkaline glutaraldehyde solution was determined using standardized suspensions of 10 species of atypical mycobacteria and compared with that for virulent Mycobacterium tuberculosis. Suspensions of M. avium, M. intracellulare and M. gordonae were more resistant to disinfection by the glutaraldehyde than were virulent tubercle bacilli while M. kansasii, M. scrofulaceum and M. szulgae were somewhat more susceptible. Mycobacterium marinum, M. smegmatis and M. fortuitum were highly sensitive to the disinfectant action of the alkaline glutaraldehyde solution. This variation in sensitivity shown by apparently closely related strains of mycobacteria to this disinfectant has important practical implications. PMID- 3096932 TI - Immunodiffusion analysis shows that Mycobacterium paratuberculosis and other mycobactin-dependent mycobacteria are variants of Mycobacterium avium. AB - Antigenic analysis by immunodiffusion has been applied to 74 strains of mycobactin-dependent mycobacteria. Thirty-eight strains were of Mycobacterium paratuberculosis from cases of Johne's disease of cattle or goats. The remaining cultures were obtained from a variety of animals and included the wood pigeon bacillus. Rabbit antisera were raised to some of the strains and these, together with antisera to M. avium and M. intracellulare, were used to examine sonicate preparations of all the cultures. All were found to be antigenically identical with M. avium and none were found to belong to M. intracellulare. A predominance of the cultures from Johne's disease belonged to the potential brunense subspecies of M. avium, and the remainder together with the majority of the other mycobactin-dependent strains belonged to the type subspecies. In view of these findings the separate species status of M. paratuberculosis is refuted and some difficulty remains in the nomenclature of strains giving rise to Johne's disease. PMID- 3096933 TI - Numerical taxonomy of Bacillus isolated from orally administered drugs. AB - Numerical taxonomy procedures were used to study 118 strains of Bacillus isolated from non-sterile drugs prepared for oral administration. Similarities between pairs of strains were calculated by the simple matching coefficient of Sokal and Michener (SSM). Each strain was tested for 60 unit characters and three clusters were defined. The strains in each cluster presented a similarity level of at least 60%. Cluster A comprised the strains identified as Bacillus cereus (SSM = 93.13%), cluster B contained three subgroups corresponding to the species B. pumilus, B. subtilis and B. licheniformis (SSM = 84.35%) and cluster C also included three subgroups that belonged to the species B. firmus, B. lentus and B. badius (SSM = 80.14%). The most discriminating tests were selected to differentiate the clusters from the subgroups. The feature with the highest discriminating power between clusters A and B was the lack of acid production from arabinose and mannitol. The Voges-Proskauer, methyl red tests and sensitivity to polymyxin B clearly distinguished cluster A from C. The Voges Proskauer test and acid production from arabinose were the best to differentiate between B and C. Bacillus pumilus and B. subtilis differed in starch hydrolysis and B. licheniformis in growing anaerobically. To discriminate B. firmus from B. lentus the most important tests were the acid production from glucose and sucrose; intermediate strains were found. Bacillus badius was differentiated from B. firmus by 10 tests, and from B. lentus by the production of urease. PMID- 3096934 TI - The use of a model system to compare the efficiency of ultrasound and agitation in the recovery of Bacillus subtilis spores from polymer surfaces. AB - The effectiveness of ultrasound and mechanical agitation for the recovery of Bacillus subtilis spores from pre-inoculated glass, polystyrene, polypropylene, polyethylene and polycarbonate surfaces was tested in the presence and absence of surfactant. Recovery from polymers was improved by the use of surfactant. Simple agitation, as frequently used in bioburden determination, is shown to be a poor method for the recovery of spores from hard surfaces. The use of ultrasound achieves recoveries over 90% only with glass, recoveries from polymers ranging from 40%-75%. Recoveries from polypropylene and polycarbonate showed poor reproducibilities. Agitation with Ballotini beads improved the reproducibility of recoveries from polymers and also in the majority of cases improved recovery levels. PMID- 3096935 TI - Regional release of cyclooxygenase products after radiation exposure of the rat. AB - The present study evaluated the regional release of cyclooxygenase products 4 h following 20 Gy gamma irradiation. Thoracic shielding reduced the radiation induced increase in immunoreactive thromboxane B2 (iTxB2) excretion to control levels while abdominal shielding partially attenuated the altered excretion of this cyclooxygenase product. To assess the role the kidneys play in the radiation induced increase in iTxB2 excretion, an in situ isolated perfused rat kidney model was developed. The excretion rate of iTxB2 from irradiated isolated perfused kidneys was not significantly different from sham-irradiated perfused kidneys. Radiation exposure did alter renal cyclooxygenase product release in that the excretion of immunoreactive prostaglandin E2 (iPG2) and immunoreactive 6 keto-PGF1 alpha was significantly increased (P less than 0.05) in irradiated isolated perfused kidneys. These data show that radiation-induced increases in iTxB2 excretion are primarily due to altered extrarenal synthesis and/or metabolism of this arachidonate metabolite. PMID- 3096936 TI - Effect of arterial PCO2 on 2-[1-14C]deoxy-D-glucose uptake by feline cerebral arteries. AB - The effect of high and low arterial CO2 on the glucose utilization of nine major cerebral arteries was studied in cats anesthetized with pentothal using the quantitative 2-[1-14C]deoxy-D-glucose autoradiographic technique. All nine cerebral arteries from animals subjected to an arterial partial pressure of CO2 (PCO2) of 20 Torr utilized significantly more (P less than 0.025) glucose than the group subjected to an arterial PCO2 of 60 Torr. Mean relative glucose utilization of the 20-Torr PCO2 group was 105 +/- 9.5 mumol X 100g-1 X min-1 (+/- SE, n = 18) as compared with 49 +/- 6 mumol X 100g-1 X min-1 (+/- SE, n = 26) for the 60-Torr PCO2 group. This study demonstrates that blood vessels can be studied in vivo using the 2-[1-14C]deoxy-D-glucose autoradiographic technique. It also demonstrates that a physiological stimulus like CO2 can produce measurable changes in glucose utilization of cerebral arteries in vivo. PMID- 3096937 TI - Cardiorespiratory responses to hypoxia in intact and bilaterally vagotomized pigeons. AB - Bilateral, cervical vagotomy in birds denervates, among other receptors, the carotid bodies. To test whether such neural section removes sensitivity to hypoxia, we measured respiratory, cardiovascular, and blood gas responses to hypoxia at 84-, 70-, and 49-Torr inspiratory O2 partial pressure (PIO2) in five pigeons with intact vagi and in five bilaterally, cervically vagotomized pigeons. Normoxic respiratory frequency (fresp) and expiratory flow rate (VE) were decreased after vagotomy. Intact pigeons showed large increases in VE in response to hypoxia, effected mostly by increases in fresp. VE also increased greatly in response to hypoxia in vagotomized pigeons, but increases were largely the result of tidal volume. O2 consumption, CO2 production, and respiratory exchange ratio increased slightly in all pigeons during hypoxia. Normoxic heart rate was greater after vagotomy; cardiac output increased in all pigeons in response to hypoxia, but stroke volume increased only in intact pigeons. During normoxia, arterial and mixed venous O2 partial pressure, O2 concentration, and pH were lower and arterial and mixed venous CO2 partial pressure was higher, after vagotomy. In all pigeons during hypoxia, arterial and mixed venous O2 and CO2 partial pressure and O2 concentration decreased and arterial and mixed venous pH increased; changes were roughly parallel in intact and vagotomized pigeons. The arteriovenous O2 concentration differences during normoxia and hypoxia were similar in all pigeons. We conclude that bilateral, cervical vagotomy in the pigeon causes hypoventilation and tachycardia during normoxia, but strong respiratory and cardiovascular responses to hypoxia are still present. PMID- 3096938 TI - Pulmonary mechanics during rapid mechanical ventilation in rabbits with saline lavaged lungs. AB - Infants with respiratory failure are frequently mechanically ventilated at rates exceeding 60 breaths/min. We analyzed the effect of ventilatory rates of 30, 60, and 90 breaths/min (inspiratory times of 0.6, 0.3, and 0.2 s, respectively) on the pressure-flow relationships of the lungs of anesthetized paralyzed rabbits after saline lavage. Tidal volume and functional residual capacity were maintained constant. We computed effective inspiratory and expiratory resistance and compliance of the lungs by dividing changes in transpulmonary pressure into resistive and elastic components with a multiple linear regression. We found that mean pulmonary resistance was lower at higher ventilatory rates, while pulmonary compliance was independent of ventilatory rate. The transpulmonary pressure developed by the ventilator during inspiration approximated a linear ramp. Gas flow became constant and the pressure-volume relationship linear during the last portion of inspiration. Even at a ventilatory rate of 90 breaths/min, 28-56% of the tidal volume was delivered with a constant inspiratory flow. Our findings are consistent with the model of Bates et al. (J. Appl. Physiol. 58: 1840-1848, 1985), wherein the distribution of gas flow within the lungs depends predominantly on resistive factors while inspiratory flow is increasing, and on elastic factors while inspiratory flow is constant. This dynamic behavior of the surfactant-depleted lungs suggests that, even with very short inspiratory times, distribution of gas flow within the lungs is in large part determined by elastic factors. Unless the inspiratory time is further shortened, gas flow may be directed to areas of increased resistance, resulting in hyperinflation and barotrauma. PMID- 3096939 TI - Analysis of postinspiratory activity of phrenic motoneurons with chemical and vagal reflexes. AB - We examined the effects of chemical and reflex drives on the postinspiratory inspiratory activity (PIIA) of phrenic motoneurons using a single-fiber technique. Action potentials from "single" fibers were recorded from the C5 phrenic root together with contralateral mass phrenic activity (also from C5) in anesthetized, paralyzed, and artificially ventilated cats with intact vagus and carotid sinus nerves. Nerve fibers were classified as "early" or "late" based on their onset of discharge in relation to mass phrenic activity during hyperoxic ventilation. Only the early fibers displayed PIIA but not the late fibers, even when their activity began earlier in inspiration with increased chemical drives. Isocapnic hypoxia increased, whereas hyperoxic hypercapnia shortened the duration of PIIA. Pulmonary stretch and "irritant" receptors inhibited PIIA. Hypercapnia and stimulation of peripheral chemoreceptors by lobeline excited both early and late units to the same extent, but hypoxic ventilation had a less marked excitatory effect on late fiber activity. Irritant receptor activation increased the activity of early more than late fibers. Hyperoxic hyperventilation eliminated late phrenic fiber activity, whereas early fibers became tonically active. Bilateral vagotomy abolished this sustained discharge in eight of nine early units, suggesting the importance of vagal afferents in producing tonic firing during hyperventilation. These results suggest that early and late phrenic fibers have different responses to chemical stimuli and to vagally mediated reflexes; late units do not discharge in postinspiratory period, whereas early fibers do; the PIIA is not affected in the same way by various chemical and vagal inputs; and early units that exhibit PIIA display tonic activity with hyperoxic hypocapnia. PMID- 3096940 TI - Pulmonary vascular responses to angiotensin II and captopril in conscious dogs. AB - Our objectives were to investigate the extent to which angiotensin II (ANG II) and converting-enzyme inhibition (CEI) exert a direct vasoactive influence on the pulmonary circulation of conscious dogs. Multipoint pulmonary vascular pressure cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava to reduce Q. The effects of ANG II infusion (60 ng X kg-1 X min-1, iv) and CEI with captopril (1 mg/kg plus 1 mg X kg-1 X h-1, iv) on pulmonary vascular P/Q plots were assessed first with the conscious dogs intact and again after combined administration of pharmacological antagonists to block sympathetic alpha- and beta-adrenergic, cholinergic, and arginine vasopressin receptors. In intact dogs, ANG II increased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure, PAP-PCWP) over the entire range of Q studied (60-120 ml X min-1 X kg-1). Conversely, CEI decreased (P less than 0.05) PAP-PCWP at each level of Q. After administration of the autonomic nervous system and arginine vasopressin receptor antagonists, ANG II again increased (P less than 0.01) and CEI decreased (P less than 0.01) PAP-PCWP over the entire range of Q studied. Thus exogenous administration of ANG II results in active, nonflow dependent constriction of the pulmonary circulation, and this effect is not dependent on the autonomic nervous system or increased circulating levels of arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096941 TI - Hemoglobin concentrations and blood gas tensions of free-diving Weddell seals. AB - Arterial blood gas tensions, pH, and hemoglobin concentrations were measured in four free-diving Weddell seals Leptonychotes weddelli. A microprocessor controlled sampling system enabled us to obtain 24 single and 31 serial aortic blood samples. The arterial O2 tension (PaO2) at rest [78 +/- 13 (SD) Torr] increased with diving compression to a maximum measured value of 232 Torr and then rapidly decreased to 25-35 Torr. The lowest diving PaO2 we measured was 18 Torr just before the seal surfaced from a 27-min dive. A consistent increase of arterial hemoglobin concentrations from 15.1 +/- 1.10 to 22.4 +/- 1.41 g/100 ml (dives less than 17 min) and to 25.4 +/- 0.79 g/100 ml (dives greater than 17 min) occurred during each dive. We suggest that an extension of the sympathetic outflow of the diving reflex possibly caused profound contraction of the Weddell seal's very large spleen (0.89% of body wt at autopsy), although we have no direct evidence. This contraction may have injected large quantities of red blood cells (2/3 of the total) into the seal's central circulation during diving and allowed arterial O2 content to remain constant for the first 15-18 min of long dives. The increase of arterial CO2 tensions during the dive and the compression increase of arterial N2 tensions were also moderated by injecting red blood cells sequestered at ambient pressure. After each dive circulating red blood cells are oxygenated and rapidly sequestered, possibly in the spleen during the first 15 min of recovery. PMID- 3096942 TI - Closed-circuit metabolic system with multiple applications. AB - A closed-circuit metabolic system has been designed and tested for multiple applications. Air pressure within a closed chamber is regulated electronically while allowing for respiratory gas exchange. Compared with a previously reported standard indirect calorimetry system, the new device had by virtue of longer duration of measurement improved precision (coefficient of variation 3% vs. 14%) during studies of O2 consumption both at room temperature and at 5 degrees C. In addition, a more physiological atmospheric environment is maintained. This system has also been utilized for simultaneously labeling groups of up to 20 weanling rats with 18O2 over a 2-day period and for exposure of rats to a hyperoxic (84% O2), normobaric environment for 4-day periods. Potential applications include maintenance of pressure (hypobaric through hyperbaric) and O2 (hypoxic through hyperoxic) controlled environments, exposure to toxic gases, study of diurnal variations in metabolic rate, measurement of metabolic expenditure with activity, and adaptation to other species including humans. PMID- 3096943 TI - Role of ornithine decarboxylase and polyamines in early postnatal lung growth. AB - We assessed the importance of ornithine decarboxylase (ODC) and polyamines in early postnatal lung growth. Lung-ODC activity in newborn rats rose rapidly after birth and was highest at 4-6 days of age. Lung putrescine and spermidine specific contents also peaked during this period, but spermine specific content remained relatively unchanged. The temporal pattern of these changes differed markedly from that in the heart, brain, and kidney where ODC activity is highest at birth then rapidly declines. The period of peak lung-ODC activity and polyamine specific content correlated with rapid increases in lung DNA content, protein content, and weight. The specific irreversible ODC inhibitor, alpha difluoromethylornithine, significantly reduced lung-ODC activity and putrescine and spermidine specific content; it also caused significant early reductions in lung DNA and protein content without simultaneously affecting body weight and appearance. Morphometrically, the lungs of alpha-difluoromethylornithine-treated rats had significantly fewer type 2 epithelial cells, interstitial cells, and capillary endothelial cells than the lungs of controls. We conclude that ODC and polyamines play an important role in postnatal lung growth and that alpha difluoromethylornithine can be used as a probe to disrupt lung growth. PMID- 3096944 TI - Effect of water immersion on cardiopulmonary physiology at high gravity (+Gz). AB - We compared the cardiopulmonary physiology of eight subjects exposed to 1, 2, and 3 Gz during immersion (35 degrees C) to the heart level with control dry rides. Immersion should almost cancel the effects of gravity on systemic circulation and should leave the lung alone to gravitational influence. During steady-state breathing we measured ventilation, O2 consumption (VO2), CO2 production, end tidal PCO2 (PACO2), and heart frequency (fH). Using CO2 rebreathing techniques, we measured cardiac output, functional residual capacity, equivalent lung tissue volume, and mixed venous O2 content, and we calculated arterial PCO2 (PaCO2). As Gz increased, ventilation, fH, and VO2 rose markedly, and PACO2 and PaCO2 decreased greatly in dry ride, but during immersion these variables changed very little in the same direction. Functional residual capacity was lower during immersion and decreased in both the dry and immersed states as Gz increased, probably reflecting closure effects. Cardiac output decreased as Gz increased in dry rides and was elevated and unaffected by Gz during immersion. We conclude that most of the changes we observed during acceleration are due to the effect on the systemic circulation, rather than to the effect on the lung itself. PMID- 3096945 TI - Pulmonary gas exchange in humans during normobaric hypoxic exercise. AB - Previous studies (J. Appl. Physiol. 58: 978-988 and 989-995, 1985) have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during heavy exercise at sea level and during hypobaric hypoxia in a chamber [fractional inspired O2 concentration (FIO2) = 0.21, minimum barometric pressure (PB) = 429 Torr, inspired O2 partial pressure (PIO2) = 80 Torr]. We used the multiple inert gas elimination technique to compare gas exchange during exercise under normobaric hypoxia (FIO2 = 0.11, PB = 760 Torr, PIO2 = 80 Torr) with earlier hypobaric measurements. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate (HR), minute ventilation, respiratory rate (RR), and blood temperature were recorded at rest and during steady-state exercise in 10 normal subjects in the following order: rest, air; rest, 11% O2; light exercise (75 W), 11% O2; intermediate exercise (150 W), 11% O2; heavy exercise (greater than 200 W), 11% O2; heavy exercise, 100% O2 and then air; and rest 20 minutes postexercise, air. VA/Q inequality increased significantly during hypoxic exercise [mean log standard deviation of perfusion (logSDQ) = 0.42 +/- 0.03 (rest) and 0.67 +/- 0.09 (at 2.3 l/min O2 consumption), P less than 0.01]. VA/Q inequality was improved by relief of hypoxia (logSDQ = 0.51 +/- 0.04 and 0.48 +/- 0.02 for 100% O2 and air breathing, respectively). Diffusion limitation for O2 was evident at all exercise levels while breathing 11% O2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096946 TI - Increased lung vascular permeability after arachidonic acid and hydrostatic challenge. AB - Arachidonic acid (AA) metabolites are known to be potent vasoactive substances in the pulmonary circulation, whereas their influence on lung vascular permeability is still uncertain. We investigated the effect of AA bolus injection on the capillary filtration coefficient (Kf,C) of isolated rabbit lungs, recirculatingly perfused with Krebs-Henseleit albumin (1%) buffer. Kf,C was measured using repetitive sudden venous pressure elevations (7.5 Torr) and time zero extrapolation of the slope of the weight gain curve. It ranged from 1.3 to 2.4 cm3 X s-1 X Torr-1 X g-1 X 10(-4) in control lungs. Pulmonary arterial injection of AA (100 microM; in presence of 20 microM indomethacin to suppress pulmonary arterial pressure rise) during an acute hydrostatic challenge, but not at zero venous pressure, caused a greater than 10-fold increase in Kf,C. Vascular compliance was not altered. Additional experiments, performed under zero-flow conditions to avoid any ambiguity in microvascular pressure, corroborated the severalfold increase in vascular permeability, detectable within 3 min after AA application during acute hydrostatic challenge. PMID- 3096947 TI - Increased vasoreactivity and chronic pulmonary hypertension following thoracic irradiation in sheep. AB - Six chronically catheterized sheep were exposed to 1,500-rad whole-lung irradiation and followed for a four-week period. Pulmonary arterial, left atrial and systemic arterial pressures, cardiac output, arterial blood gases, and pH were measured at base line and biweekly following radiation. Pulmonary vasoreactivity to 12% O2, 100% O2, and an analogue of prostaglandin H2 (PGH2-A) was also assessed. Five nonirradiated sheep served as controls. By the 2nd wk following irradiation, pulmonary vascular resistance had doubled. Final pulmonary arterial pressure was increased 50% over the base-line value (base line = 14 +/- 1 cm H2O; final 22 +/- 2; mean +/- SE; P less than 0.05). Arterial PO2 was decreased to approximately 70 Torr throughout the study. In addition, pulmonary vasoreactivity to PGH2-A, but not to breathing 12 or 100% O2, was significantly increased above base line in the irradiated animals (P less than 0.05). Morphometric techniques applied to the lungs in which the pulmonary arterial circulation was distended with barium gelatin mixture, showed extension of muscle into the distal intra-acinar arteries, and a reduction in both the external diameter and the number of barium-filled peripheral arteries in the irradiated animals. Thus thoracic irradiation results in functional and structural changes of chronic pulmonary hypertension and increased pulmonary vasoreactivity to PGH2 A. The structural changes in the peripheral pulmonary arterial bed may contribute to the increased pulmonary vascular reactivity following thoracic irradiation. PMID- 3096948 TI - Effects of mean airway pressure on gas transport during high-frequency ventilation in dogs. AB - In 10 anesthetized, paralyzed, supine dogs, arterial blood gases and CO2 production (VCO2) were measured after 10-min runs of high-frequency ventilation (HFV) at three levels of mean airway pressure (Paw) (0, 5, and 10 cmH2O). HFV was delivered at frequencies (f) of 3, 6, and 9 Hz with a ventilator that generated known tidal volumes (VT) independent of respiratory system impedance. At each f, VT was adjusted at Paw of 0 cmH2O to obtain a eucapnia. As Paw was increased to 5 and 10 cmH2O, arterial PCO2 (PaCO2) increased and arterial PO2 (PaO2) decreased monotonically and significantly. The effect of Paw on PaCO2 and PaO2 was the same at 3, 6, and 9 Hz. Alveolar ventilation (VA), calculated from VCO2 and PaCO2, significantly decreased by 22.7 +/- 2.6 and 40.1 +/- 2.6% after Paw was increased to 5 and 10 cmH2O, respectively. By taking into account the changes in anatomic dead space (VD) with lung volume, VA at different levels of Paw fits the gas transport relationship for HFV derived previously: VA = 0.13 (VT/VD)1.2 VTf (J. Appl. Physiol. 60: 1025-1030, 1986). We conclude that increasing Paw and lung volume significantly decreases gas transport during HFV and that this effect is due to the concomitant increase of the volume of conducting airways. PMID- 3096949 TI - Inspiratory-to-expiratory time ratio and alveolar ventilation during high frequency ventilation in dogs. AB - It has been suggested that the increase in inspiratory flow rate caused by a decrease in the inspiratory-to-expiratory time ratio (I:E) at a constant tidal volume (VT) could increase the efficiency of ventilation in high-frequency ventilation (HFV). To test this hypothesis, we studied the effect of changing I:E from 1:1 to 1:4 on steady-state alveolar ventilation (VA) at a given VT and frequency (f) and at a constant mean lung volume (VL). In nine anesthetized, paralyzed, supine dogs, HFV was performed at 3, 6, and 9 Hz with a ventilator that delivered constant inspiratory and expiratory flow rates. Mean airway pressure was adjusted so that VL was maintained at a level equivalent to that of resting FRC. At each f and one of the I:E chosen at random, VT was adjusted to obtain a eucapnic steady state [arterial pressure of CO2 (PaCO2) = 37 +/- 3 Torr]. After 10 min of each HFV, PaCO2, arterial pressure of O2 (PaO2), and CO2 production (VCO2) were measured, and I:E was changed before repeating the run with the same f and VT. VA was calculated from the ratio of VCO2 and PaCO2. We found that the change of I:E from 1:1 to 1:4 had no significant effects on PaCO2, PaO2, and VA at any of the frequencies studied. We conclude, therefore, that the mechanism or mechanisms responsible for gas transport during HFV must be insensitive to the changes in inspiratory and expiratory flow rates over the VT-f range covered in our experiments. PMID- 3096950 TI - Arterial blood gases and acid-base status of dogs during graded dynamic exercise. AB - The objective of this study was to determine whether arterial PCO2 (PaCO2) decreases or remains unchanged from resting levels during mild to moderate steady state exercise in the dog. To accomplish this, O2 consumption (VO2) arterial blood gases and acid-base status, arterial lactate concentration ([LA-]a), and rectal temperature (Tr) were measured in 27 chronically instrumented dogs at rest, during different levels of submaximal exercise, and during maximal exercise on a motor-driven treadmill. During mild exercise [35% of maximal O2 consumption (VO2 max)], PaCO2 decreased 5.3 +/- 0.4 Torr and resulted in a respiratory alkalosis (delta pHa = +0.029 +/- 0.005). Arterial PO2 (PaO2) increased 5.9 +/- 1.5 Torr and Tr increased 0.5 +/- 0.1 degree C. As the exercise levels progressed from mild to moderate exercise (64% of VO2 max) the magnitude of the hypocapnia and the resultant respiratory alkalosis remained unchanged as PaCO2 remained 5.9 +/- 0.7 Torr below and delta pHa remained 0.029 +/- 0.008 above resting values. When the exercise work rate was increased to elicit VO2 max (96 +/- 2 ml X kg-1 X min-1) the amount of hypocapnia again remained unchanged from submaximal exercise levels and PaCO2 remained 6.0 +/- 0.6 Torr below resting values; however, this response occurred despite continued increases in Tr (delta Tr = 1.7 +/- 0.1 degree C), significant increases in [LA-]a (delta [LA-]a = 2.5 +/- 0.4), and a resultant metabolic acidosis (delta pHa = -0.031 +/- 0.011). The dog, like other nonhuman vertebrates, responded to mild and moderate steady-state exercise with a significant hyperventilation and respiratory alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3096951 TI - Nonocclusive chronic vascular catheterization of conscious unrestrained baboons. AB - A surgical technique is described for chronic arterial and venous catheterization of unrestrained adult baboons. Vascular access was achieved through a small (5 cm) abdominal incision and an extraperitoneal approach to the iliac vessels, which minimizes postoperative morbidity, discomfort, and restriction of movement. The method permits secure but nonocclusive catheterization, confirmed by angiography. Catheters were removed without further surgery, leaving the baboons intact for reuse. Catheters placed in the distal common or proximal external iliac vessels were all patent when removed at 46-61 days. The results demonstrate arterial pressure, pulse rates, drug administration, blood sampling, and plasma volume measurement as examples of the technique's application in conscious unrestrained baboons. PMID- 3096952 TI - Cytomorphological lesions induced by chemotherapeutic agents in transitional cell carcinoma in vitro. AB - Transitional cell carcinoma from 20 patients and two human cell lines were maintained in short-term tissue culture. Each was studied ultrastructurally before and after incubation with cisplatinum, adriamycin, or mitomycin C. Sequential ultrastructural changes were noted and were found to be specific for each agent tested. Ultrastructural changes in the nucleoli were produced by exposure to cisplatinum or mitomycin C; alterations in the heterochromatin of the nuclei were characteristic of treatment with adriamycin. The changes in the nucleoli seen with cisplatinum have not been described previously and support an alkylating property as a mechanism of action. Intravesical chemotherapeutic agents are now commonly used in clinical treatments. The morphological changes produced by these agents are specific and may be seen in the clinical setting. PMID- 3096953 TI - Malignant transformation of NIH-3T3 and CV-1 cells by a helical mycoplasma, Spiroplasma mirum, strain SMCA. AB - A helical mycoplasma, Spiroplasma mirum strain SMCA, produced malignant transformation in mouse NIH 3T3 cells and monkey kidney CV-1 cells. The transformed cells exhibited morphological changes consistent with the transformed phenotype, grew in soft agar and produced tumors in athymic and BALB/c mice. Transmission electron microscopy revealed structures morphologically similar to mycoplasmas present in the cytoplasm of transformed but not untransformed 3T3 cells. The time of inoculation of S. mirum SMCA to 3T3 cells and the passage level of 3T3 cells affected transformation. PMID- 3096954 TI - Use of the Bacillus subtilis subtilisin signal peptide for efficient secretion of TEM beta-lactamase during growth. AB - We report the development of an efficient Bacillus subtilis secretory system, with the secreted product stably maintained in the medium for 100 h. The system is based on characterization of the subtilisin signal peptidase cleavage site and promoters, catabolite repression of sporulation, presence of a vegetative secreting mechanism, and availability of a protease-deficient strain. PMID- 3096955 TI - ATP-driven calcium transport in membrane vesicles of Streptococcus sanguis. AB - Calcium transport was investigated in membrane vesicles prepared from the oral bacterium Streptococcus sanguis. Procedures were devised for the preparation of membrane vesicles capable of accumulating 45Ca2+. Uptake was ATP dependent and did not require a proton motive force. Calcium transport in these vesicles was compared with 45Ca2+ accumulation in membrane vesicles from Streptococcus faecalis and Escherichia coli. The data support the existence of an ATP-driven calcium pump in S. sanguis similar to that in S. faecalis. This pump, which catalyzes uptake into membrane vesicles, would be responsible for extrusion of calcium from intact cells. PMID- 3096956 TI - Carboxypeptidase activity in human mycoplasmas. AB - Mycoplasma salivarium produced citrulline, ammonia, and ATP from N-benzoylglycyl L-arginine. The activity was inhibited by EDTA and was therefore concluded to be due to an arginine-specific carboxypeptidase. The activity was also found to exist in M. orale, M. buccale, M. faucium, and M. hominis. PMID- 3096957 TI - Cell surface antigens during submerged development of Myxococcus xanthus examined with monoclonal antibodies. AB - Eighteen monoclonal antibodies directed against cell surface antigens of Myxococcus xanthus were followed by enzyme-linked immunosorbent assay. Three of the monoclonal antibodies were specifically directed against antigens present only on cells undergoing fruiting body development. These cell surface antigens became detectable by the early preaggregation stage (2 to 4 h) of development and increased until early aggregation (9 to 10 h), after which the concentrations of two of the cell surface antigens remained constant and the concentration of the third decreased. The remaining 15 monoclonal antibodies recognized cell surface antigens that were shared by vegetative and developing cells. Based on their relative concentrations during development, these shared antigens can be grouped into three classes. In the first class antigen concentration remained constant, in the second it decreased, and in the third it increased. Western blots of cell surface antigens were probed with monoclonal antibodies. Five monoclonal antibodies reacted with material in distinct bands, five monoclonal antibodies reacted with multiple, diffuse bands, and eight monoclonal antibodies were not reactive in Western blots. PMID- 3096958 TI - Polysaccharide covalently linked to the peptidoglycan of the cyanobacterium Synechocystis sp. strain PCC6714. AB - A polysaccharide was found to be covalently linked to the peptidoglycan of the unicellular cyanobacterium Synechocystis sp. strain PCC6714 via phosphodiester bonds. It could be cleaved from the peptidoglycan-polysaccharide (PG-PS) complex by hydrofluoric acid (HF) treatment in the cold (48% HF, 0 degrees C, 48 h) yielding a pure, HF-insoluble peptidoglycan fraction and an HF-soluble polysaccharide fraction. The PG-PS complex was isolated from the Triton X-100 insoluble cell wall fraction by hot sodium dodecyl sulfate treatment and digestion with proteases. Digestion of the complex with N-acetylmuramidase released the glycopeptide-linked polysaccharide, which was further purified by dialysis and gel filtration on Sephadex G-50 and G-200. The polysaccharide consisted of glucosamine, mannosamine, galactosamine, mannose, and glucose and had a molecular weight of 25,000 to 30,000. Muramic acid-6-phosphate was identified as the binding site of the covalently linked, nonphosphorylated polysaccharide as revealed by chemical analysis of linkage fragments of the PG-PS complex. PMID- 3096959 TI - Linearization of donor DNA during plasmid transformation in Neisseria gonorrhoeae. AB - We examined the fate of plasmid DNA after uptake during transformation in Neisseria gonorrhoeae. An 11.5-kilobase plasmid, pFA10, was processed to linear double-stranded DNA during uptake by competent cells, but cleavage of pFA10 was not site specific. A minority of pFA10 entered as open circles. A 42-kilobase plasmid, pFA14, was degraded into small fragments during uptake; no intracellular circular forms of pFA14 were evident. Since pFA10 DNA linearized by a restriction enzyme was not further cut during uptake, the endonucleolytic activity associated with entry of plasmid DNA appeared to act preferentially on circular DNA. Although linear plasmid DNA was taken up into a DNase-resistant state as efficiently as circular DNA, linear plasmid DNA transformed much less efficiently than circular plasmid DNA. These data suggest that during entry transforming plasmid DNA often is processed to double-stranded linear molecules; transformants may arise when some molecules are repaired to form circles. Occasional molecules which enter as intact circles may also lead to transformants. PMID- 3096960 TI - Colonial heterogeneity of Thiobacillus versutus. AB - In acetate-limited chemostat cultures started with single-colony cultures of Thiobacillus versutus, a mutant appeared after approximately 85 volume changes. The inhomogeneity of the culture was detected by the development of two different types of colonies on agar plates. When a pure culture of the mutant was grown in a chemostat, parent colonies appeared after almost the same period of time. Electron micrographs of the mutant grown on butyrate showed the presence of fibrils surrounding the cells. The cells of the parent strain were bald when grown under the same conditions. The growth kinetics of the parent and the mutant were investigated in batch cultures with a variety of substrates and were found to be identical. Major differences between the two strains were observed during growth on mannitol; the mutant attained a lower yield and excreted large amounts of extracellular polysaccharides. PMID- 3096961 TI - Effect of L-amino acids on Mucor rouxii dimorphism. AB - Mucor rouxii organisms growing aerobically and exponentially on a well-defined minimal medium are able to differentiate as yeasts or as mycelia, depending on the amino acid as the nitrogen source. When certain amino acids were used as the nitrogen source, spores differentiated only as hyphae, whereas other amino acids gave rise to other morphological forms having different ratios of yeasts to hyphae. In both hyphal and yeast cultures, an aerobic metabolism was predominant, as shown by determining several metabolic parameters such as oxygen tension, glucose consumption, ethanol production, and CO2 release. A complete conversion of yeasts to hyphae was obtained by the appropriate change in the amino acid used as nitrogen source. By preparing spheroplasts from mycelial cultures and transferring them to media with amino acids that induce yeast formation, a 50% yield in the reverse transformation was achieved. A correlation between the change in pH of the medium and cell morphology was observed in different growth conditions. Decrease in the pH of the medium preceded the appearance of hyphae. Also, when the initial pH of the medium was increased, aspartate-containing cultures developed mainly as mycelia, instead of yeasts, with a corresponding decrease in the final pH. PMID- 3096962 TI - Characterization of a cloned Bacillus subtilis gene that inhibits sporulation in multiple copies. AB - We have isolated a 1.0-kilobase fragment of the Bacillus subtilis chromosome which, when present in high-copy-number plasmids, caused a sporulation-proficient strain to become phenotypically sporulation deficient. This is referred to as the sporulation inhibition (Sin) phenotype. This DNA fragment, in multicopy, also inhibited the production of extracellular protease activity, which normally appears at the beginning of stationary growth. The origin of the fragment was mapped between the dnaE and spo0A genes on the B. subtilis chromosome, and its complete DNA sequence has been determined. By analysis of various deletions and a spontaneous mutant the Sin function was localized to an open reading frame (ORF) predicted from the DNA sequence. Inactivation of this ORF in the chromosome did not affect the ability of cells to sporulate. However, the late-growth-associated production of proteases and alpha-amylase was elevated in these cells. The predicted amino acid sequence of the protein encoded by this ORF had a DNA binding domain, typically present in several regulatory proteins. We propose that the sin ORF encodes a regulatory protein that is involved in the transition from vegetative growth to sporulation. PMID- 3096963 TI - Diglycosyl diacylglycerol of Mycobacterium tuberculosis. AB - A diglycosyl diacylglycerol was isolated from Mycobacterium tuberculosis, and its structure was established by a combination of methylation analysis, 1H nuclear magnetic resonance, and fast atom bombardment-mass spectrometry. It is a 1,2 diacyl-[beta-D-glucopyranosyl(1"----6')-beta-D-glucopyranosyl(1'---- 3)]- sn glycerol and exists in at least five molecular species differing in fatty acyl substituents. The major constituent fatty acids were identified as iso- and anteisopentadecanoate, iso- and n-hexadecanoate, and iso- and anteisoheptadecanoate. Although glycosyl diacylglycerols are common membrane components of gram-positive bacteria, this report represents the first substantial evidence for the presence of a glycosyl diacylglycerol within a member of the Mycobacterium genus. Although the glycolipid is not a major component of M. tuberculosis, it reacts readily in enzyme-linked immunosorbent assay against rabbit antibodies raised against whole bacteria and thus may be useful for the serodiagnosis of tuberculosis. PMID- 3096964 TI - Induction of SOS functions by alkaline intracellular pH in Escherichia coli. AB - Alkalinization of intracellular pH (pHi) causes an increase in UV resistance in wild-type and pH-sensitive mutant (DZ3) cells of Escherichia coli. Utilizing cells transformed with a plasmid (pA7) which bears the uvrA promoter fused to galK galactokinase structural gene, it was shown that alkaline pHi leads to an increase in the specific activity of galactokinase. This effect was not displayed in a mutant bearing a recA-insensitive lexA gene, nor in cells harboring a plasmid (pA8) in which the galK is fused to a lexA-insensitive uvrA promoter. Hence, the effects of pHi on cells functions may involve the lexA product of the SOS system. PMID- 3096965 TI - Glucose represses formation of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine and isopenicillin N synthase but not penicillin acyltransferase in Penicillium chrysogenum. AB - The content of alpha-aminoadipyl-cysteinyl-valine, the first intermediate of the penicillin biosynthetic pathway, decreased when Penicillium chrysogenum was grown in a high concentration of glucose. Glucose repressed the incorporation of [14C]valine into alpha-aminoadipyl-cysteinyl-[14C]valine in vivo. The pool of alpha-aminoadipic acid increased sevenfold in control (lactose-grown) penicillin producing cultures, coinciding with the phase of rapid penicillin biosynthesis, but this increase was very small in glucose-grown cultures. Glucose stimulated homocitrate synthase and saccharopine dehydrogenase activities in vivo and increased the incorporation of lysine into proteins. These results suggest that glucose stimulates the flux through the lysine biosynthetic pathway, thus preventing alpha-aminoadipic acid accumulation. The repression of alpha aminoadipyl-cysteinyl-valine synthesis by glucose was not reversed by the addition of alpha-aminoadipic acid, cysteine, or valine. Glucose also repressed isopenicillin N synthase, which converts alpha-aminoadipyl-cysteinyl-valine into isopenicillin N, but did not affect penicillin acyltransferase, the last enzyme of the penicillin biosynthetic pathway. PMID- 3096966 TI - Integrable alpha-amylase plasmid for generating random transcriptional fusions in Bacillus subtilis. AB - An integrable plasmid, pOK4, which replicated independently in Escherichia coli was constructed for generating transcriptional fusions in vivo in Bacillus DNA. It did not replicate independently in Bacillus subtilis, but it could be made to integrate into the chromosome of B. subtilis if sequences homologous to chromosomal sequences were inserted into it. It had a selectable marker for chloramphenicol resistance and carried unique sites for EcoRI and SmaI just to the 5' side of a promoterless alpha-amylase gene from Bacillus licheniformis. When B. subtilis DNA fragments were ligated into one of these sites and the ligation mixture was used to transform an alpha-amylase-negative B. subtilis strain, chloramphenicol-resistant transformants could be isolated conveniently. Many of these were alpha-amylase positive, owing to the fusion of the plasmid amylase gene to chromosomal operons. In principle, because integration need not be mutagenic, it is possible to obtain fusions to any chromosomal operon. The site of each integration can be mapped, and the flanking sequences can be cloned into E. coli. The alpha-amylase gene can be used to detect regulated genes. We used it as an indicator to detect operons which are DNA-damage-inducible (din), and we identified insertions in both SP beta and PBSX prophages. PMID- 3096967 TI - Purification of extracellular lipase from Pseudomonas aeruginosa. AB - Lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) was excreted by Pseudomonas aeruginosa PAC1R during the late logarithmic growth phase. Characterization of cell-free culture supernatants by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the presence of significant amounts of lipopolysaccharide, part of which seemed to be tightly bound to lipase. After concentration of culture supernatants by ultrafiltration, lipase lipopolysaccharide complexes were dissociated by treatment with EDTA-Tris buffer and subsequent sonication in the presence of the zwitterionic detergent 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate. The solubilized lipase was purified by isoelectric focusing in an agarose gel containing the same detergent; the lipase activity appeared in a single peak corresponding to a distinct band in the silver-stained gel. The isoelectric point was 5.8. Analysis of purified lipase by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and scanning revealed an apparent molecular weight of 29,000 and a specific activity of 760 mu kat/mg of protein. Estimations based on these data showed that a single P. aeruginosa cell excreted about 200 molecules of lipase, each having a molecular activity of 2.2 X 10(4) per s. PMID- 3096968 TI - Heat shock proteins of vegetative and fruiting Myxococcus xanthus cells. AB - The heat shock response of Myxococcus xanthus was investigated and characterized. When shifted from 28 to 40 degrees C, log-phase cells rapidly ceased growth, exhibited a 50% reduction in CFU, and initiated the synthesis of heat shock proteins (HTPs). Heat-shocked log-phase M. xanthus cells labeled with [35S]methionine were found to produce 18 major HTPs. The HTPs, analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography, were characterized with regard to molecular mass, subcellular location (periplasm, membrane, or cytoplasm), and temperature required for expression. Most HTPs were expressed at 36 degrees C, the optimum growth temperature of M. xanthus. Cells preincubated at 36 degrees C for 1 h before being shifted to 40 degrees C demonstrated increased thermotolerance compared with cells shifted directly from 28 to 40 degrees C. The HTPs produced by heat-shocked starvation-induced fruiting cells and glycerol-induced sporulating cells were also analyzed and characterized. Thirteen HTPs were detected in fruiting cells shifted from 28 to 40 degrees C. Six of these HTPs were not seen in vegetative M. xanthus cells. Log phase cells induced to sporulate by the addition of glycerol produced 17 HTPs after being shifted to 40 degrees C. These HTPs were found to be a mixture of HTPs detected in heat-shocked log-phase cells and heat-shocked fruiting cells. PMID- 3096969 TI - Nucleotide sequence of the penicillinase repressor gene penI of Bacillus licheniformis and regulation of penP and penI by the repressor. AB - Bacillus licheniformis penicillinase genes, penP and penI, are coded on a 4.2 kilobase EcoRI fragment of pTTE21 (T. Imanaka, T. Tanaka, H. Tsunekawa, and S. Aiba, J. Bacteriol. 147:776-186, 1981). The EcoRI fragment was subcloned in a low copy-number plasmid pTB522 in Bacillus subtilis. B. subtilis carrying the recombinant plasmid pPTB60 (Tcr penP+ penI+) was chemically mutagenized. Of about 150,000 colonies, two penI(Ts) mutant plasmids, pPTB60D13 and pPTB60E24, were screened by the plate assay at 30 and 48 degrees C for penicillinase. By constructing recombinant plasmids between wild-type and mutant plasmids, the mutation points were shown to be located in a 1.7-kilobase EcoRI-PstI fragment. The EcoRI-PstI fragments of the wild-type plasmid and two mutant plasmids were sequenced. A large open reading frame, composed of 384 bases and 128 amino acid residues (molecular weight, 14,983), was found. Since the mutation points were located at different positions in the protein coding region (Ala to Val for pPTB60D13 and Pro to Leu for pPTB60E24), the coding region was concluded to be the penI gene. A Shine-Dalgarno sequence was found 7 bases upstream from the translation start site (ATG). A probable promoter sequence which is very similar to the consensus sequence was also found upstream of the penP promoter, but in the opposite direction. A consensus twofold symmetric sequence (AAAGTATTA CATATGTAAGNTTT) which might have been used as a repressor binding region was found downstream and in the midst of the penP promoter and also downstream of the penI promoter. The regulation of penP and penI by the repressor is discussed. PMID- 3096970 TI - Translational autoregulation of ermC 23S rRNA methyltransferase expression in Bacillus subtilis. AB - ermC specifies an rRNA methyltransferase that confers resistance to erythromycin. The expression of this determinant is induced by the addition of erythromycin. The induction mechanism has been shown to operate posttranscriptionally, and its mechanism has been elucidated. We now show that synthesis of the ermC gene product in Bacillus subtilis is also autoregulated by a mechanism operating on the level of translation. The synthesis of methyltransferase was shown to be gene dosage compensated by Western blot analysis. Several mutants were analyzed that specify altered ermC gene products and are deregulated. Analysis of mutants and of the wild-type strain by Northern blotting demonstrated that autoregulation is posttranscriptional. We suggest a translational repression model in which the ermC methyltransferase binds to its own mRNA, at a region that resembles the methylation target site on 23S rRNA. The overall control of ermC expression is discussed in light of these multiple regulatory mechanisms. PMID- 3096971 TI - Comparative action of glyphosate as a trigger of energy drain in eubacteria. AB - Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa, each possessing a 5-enolpyruvylshikimate 3-phosphate synthase that is sensitive to inhibition by glyphosate [N-(phosphonomethyl)glycine], provide a good cross-section of organisms exemplifying the biochemical diversity of the aromatic pathway targeted by this potent antimicrobial compound. The pattern of growth inhibition, the alteration in levels of aromatic-pathway enzymes, and the accumulation of early pathway metabolites after the addition of glyphosate were distinctive for each organism. Substantial intracellular shikimate-3-phosphate accumulated in response to glyphosate treatment in all three organisms. Both E. coli and P. aeruginosa, but not B. subtilis, accumulated near-millimolar levels of shikimate-3-phosphate in the culture medium. Intracellular backup of common-pathway precursors of shikimate-3-phosphate was substantial in B. subtilis, moderate in P. aeruginosa, and not detectable in E. coli. The full complement of aromatic amino acids prevented growth inhibition and metabolite accumulation in E. coli and P. aeruginosa where amino acid end products directly control early-pathway enzyme activity. In contrast, the initial prevention of growth inhibition in the presence of aromatic amino acids in B. subtilis was succeeded by progressively greater growth inhibition that correlated with rapid metabolite accumulation. In B. subtilis glyphosate can decrease prephenate concentrations sufficiently to uncouple the sequentially acting loops of feedback inhibition that ordinarily link end product excess to feedback inhibition of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase by prephenate. The consequential unrestrained entry is an energy-rich substrates into the aromatic pathway, even in the presence of aromatic amino acid end products, is an energy drain that potentially accounts for the inability of end products to fully reverse glyphosate inhibition in B. subtilis. Even in E. coli after glyphosate inhibition and metabolite accumulation were allowed to become fully established, a transient period where end products were capable of only partial reversal of growth inhibition occurred. The distinctive metabolism produced by dissimilation of different carbon sources also profound effects upon glyphosate sensitivity. PMID- 3096972 TI - Characterization of heat shock in Bacillus subtilis. AB - We characterized the general properties of the heat shock response in Bacillus subtilis W168, B. subtilis JH642, and an spo0A mutant by using pulse-labeling of bacterial proteins and one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The transfer of cells from 37 to 50 degrees C repressed synthesis of most cellular proteins and led to the induction of at least 26 distinct heat shock proteins after about 3 min. Ethanol (4% [vol/vol]) induced a similar set of proteins, but somewhat more slowly. Synthesis of the majority of heat shock proteins at 50 degrees C returned to a steady-state level 20 to 40 min after the shock. Although no B. subtilis heat shock protein has yet been extensively characterized, three of these proteins were found to be immunologically related to the Escherichia coli heat shock proteins Dnak, Lon, and GroEL. Synthesis of both sigma 28 and sigma 43 proteins was sharply reduced during heat shock. Although a spo0A amber mutation blocks transcription from promoters used by at least two minor B. subtilis sigma factors, it did not alter the kinetics or general properties of the heat shock response. PMID- 3096973 TI - Cloning, expression, and characterization of the Anabaena thioredoxin gene in Escherichia coli. AB - The gene encoding thioredoxin in Anabaena sp. strain PCC 7119 was cloned in Escherichia coli based on the strategy that similarity between the two thioredoxins would be reflected both in the gene sequence and in functional cross reactivity. DNA restriction fragments containing the Anabaena thioredoxin gene were identified by heterologous hybridization to the E. coli thioredoxin gene following Southern transfer, ligated with pUC13, and used to transform an E. coli strain lacking functional thioredoxin. Transformants that complemented the trxA mutation in E. coli were identified by increased colony size and confirmed by enzyme assay. Expression of the cloned Anabaena thioredoxin gene in E. coli was substantiated by subsequent purification and characterization of the algal protein from E. coli. The amino acid sequence derived from the DNA sequence of the Anabaena gene was identical to the known amino acid sequence of Anabaena thioredoxin. The E. coli strains which expressed Anabaena thioredoxin complemented the TrxA- phenotype in every respect except that they did not support bacteriophage T7 growth and had somewhat decreased ability to support bacteriophages M13 and f1. PMID- 3096974 TI - Cloning and expression in Escherichia coli of the gene for an Arthrobacter beta (1----3)-glucanase. AB - When inserted in the correct orientation at the BamHI site of plasmid YRp7, an 8.6-kilobase BamHI fragment of Arthrobacter sp. strain YCWD3 DNA gave Escherichia coli HB101 cells harboring the recombinant plasmid pBX20 the ability to lyse bakers' yeast cell walls or bakers' yeast glucan in agar medium. An extract of the transformed E. coli cells contained an endo-beta-(1----3)-glucanase with the same activity pattern as that of glucanase I produced by Arthrobacter sp. strain YCWD3. Although part of the glucanase activity was contributed by apparently defective molecules, two protein species were found which had high lytic activity on yeast cell walls and adsorbed to microcrystalline cellulose, and both had a single constituent polypeptide with a molecular weight of about 55,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In these properties the protein species were indistinguishable from those glucanase I protein species of Arthrobacter sp. strain YCWD3 which we believe are nearly the intact molecule. We conclude that the cloned fragment of Arthrobacter sp. strain YCWD3 DNA contains the structural gene for glucanase I. A recombinant plasmid obtained by subcloning a PstI fragment of pBX20 into pBR322 caused the transformed E. coli cells to produce apparently defective glucanase molecules only. This observation serves as additional supporting evidence for our conclusion. PMID- 3096975 TI - Isolation and nucleotide sequence analysis of the ferredoxin I gene from the cyanobacterium Anacystis nidulans R2. AB - Two mixed oligonucleotide probes derived from conserved regions of the Synechocystis sp. strain PCC 6714 ferredoxin amino acid sequence were utilized to isolate an Anacystis nidulans R2 clone containing the ferredoxin I gene. Nucleotide sequence analysis revealed a 297-base-pair (bp) open reading frame with a deduced amino acid sequence having high homology to other cyanobacterial ferredoxins. Assuming proteolytic cleavage of the initial methionine residue, the molecular weight of the mature A. nidulans R2 ferredoxin was 10,370. The initial methionine residue was preceded by a probable ribosome-binding site sequence, AGGA. Northern hybridization analysis with the cloned ferredoxin gene indicated an RNA transcript of approximately 450 bp. S1 nuclease mapping localized the transcription start site to a position 64 bases upstream from the initial methionine residue. The nucleotide sequence 14 to 8 bp preceding the transcription start site resembled a typical Escherichia coli promoter, but the sequence in the -35 region did not. Southern hybridization detected only a single copy of the ferredoxin sequence in the A. nidulans R2 genome. PMID- 3096977 TI - Oxygenation-linked changes in the ultraviolet absorption and circular dichroism spectra of spiny lobster hemocyanin. AB - As an approach to elucidate the mechanism of the protein structure change in the cooperative ligand binding, the UV difference and CD spectra of aromatic residues in Panulirus japonicus (spiny lobster) hemocyanin were examined. The native hemocyanin showed an O2-induced narrow-banded change in the absorption spectrum around 290 nm, which was not affected by pH in the range of 7.5 to 9.5. When the native hexameric protein was stripped of divalent cations with EDTA (at pH 7.5), the magnitude of the narrow-banded difference was reduced to about half, whereas it was almost completely abolished on dissociation into subunits (stripped at pH 9.5). The magnitude of the absorption change was found to be proportional to the degree of O2 saturation in the native and stripped hemocyanins. It was inferred that the spectral difference reflects a tertiary structure change directly linked to the oxygenation, though it depends greatly on the subunit association. Panulirus hemocyanin showed negative CD bands in the region of 260 to 300 nm, the intensities of which were considerably reduced by oxygenation and also by dissociation into subunits. PMID- 3096976 TI - Mutation plus amplification of a transducer gene disrupts general chemotactic behavior in Escherichia coli. AB - Transducers are transmembrane receptor proteins that generate intracellular signals on stimulation and participate in adaptation by appropriate changes in the level of methylation. The transducer mutation trg-21 conferred a Trg- phenotype and defective taxis to galactose and ribose but a normal response to other attractants when present in a single chromosomal copy. Amplification of trg 21 by a multicopy plasmid made host cells generally nonchemotactic. The dominant phenotype resulted from a strong counterclockwise rotational bias of flagellar motors in Che- cells. Apparently, the Trg21 transducer sends a continuous counterclockwise signal to flagella independent of tactic stimulation. It appears that the cell has a homeostatic capacity that is sufficient to compensate for the effect of mutant transducers produced from a single chromosomal copy of trg-21, but the capacity is exceeded in cells that have multiple copies of the gene. The Trg21 protein did not have a significant effect on methylesterase activity, indicating that the two global effects of a stimulated transducer, that is, on flagellar rotation and on modification enzymes, can occur independently. The mutant protein exhibited essentially normal turnover of methyl groups but had a drastic defect in deamidation which thus reduced the number of methyl-accepting sites. The trg-21 mutation substitutes a threonine for Ala-419. This alanine is a conserved residue in all sequenced transducers and is in a region of the carboxy terminal domain in which homology among the transducers is very high. The Trg21 phenotype implicates this conserved region in the generation of the excitatory signal which is directed at the flagella. PMID- 3096978 TI - Induction of alkaline phosphatase and its transport to cell surface in primary culture of rat hepatocytes: effect of the antimicrotubular agent colchicine. AB - We have examined the effect of colchicine on the induction of alkaline phosphatase and its transport to the cell surface in a primary culture of rat hepatocytes. When freshly isolated hepatocytes were subjected to primary culture, alkaline phosphatase activity increased linearly starting at 6 h and reached a maximum level (about 10 times the initial activity) at 24 h after seeding. Radioimmunoassay with 125I-(anti-alkaline phosphatase)-IgG confirmed that the increase in enzyme activity was due to the increased amount of enzyme protein. The presence of colchicine in the culture medium (10-50 microM) did not cause an additive effect on the enzyme induction, in contrast to the previous results obtained in in vivo experiments (Ikehara, Y. et al. (1978) J. Biochem. 84, 1335 1338; Oda, K. & Ikehara, Y. (1981) Biochim. Biophys. Acta 640, 398-408). However, translocation of the induced enzyme to the cell surface was inhibited by colchicine in a dose-dependent manner. These results suggest that the enzyme induction by colchicine observed in vivo might not be due to its direct effect on hepatocytes, and that microtubules are involved in intracellular transport of the newly synthesized membrane protein. PMID- 3096979 TI - Pulmonary microsomal cytochrome P-450 from 3-methylcholanthrene-treated hamsters: purification, characterization, and metabolism of benzo(a)pyrene. AB - A major form of pulmonary cytochrome P-450 (pulmonary P-450MC) was purified approximately 165-fold from lung microsomes of 3-methylcholanthrene (MC)-treated hamsters. The purified preparation contained 14.2 nmol of cytochrome P-450 (P 450) per mg protein and was essentially free from NADPH-cytochrome P-450 (cytochrome c)-reductase (NADPH-reductase) and epoxide hydrolase. Pulmonary P 450MC exhibits an absorption maximum at 446.5 nm in the difference spectrum of reduced hemoprotein-CO complex, and a low-spin state of ferric iron in the heme. By sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, the molecular weight of pulmonary P-450MC was estimated to be 56,000. In a reconstituted system, pulmonary P-450MC efficiently catalyzed benzo(a)pyrene (BP) hydroxylation, but showed low activities for 7-ethoxycoumarin O-deethylation and benzphetamine N-demethylation. In Ouchterlony double diffusion analysis, hamster pulmonary P-450MC reacted to the antibody prepared against rat hepatic P-450MC to form a faint precipitation line with a spur, indicating that the two P-450MCs have a common antigenic site but are not immunologically identical. When incubated with [14C]BP in a reconstituted system containing NADPH-reductase and epoxide hydrolase, hamster pulmonary P-450MC formed much higher amounts of BP diols, especially 7,8-diol, than were formed by rat pulmonary P-450MC. PMID- 3096980 TI - Structures of galactose-containing oligosaccharides of alpha-mannosidase from porcine kidney. AB - Oligosaccharides of a non-oligomannoside type were released from porcine alpha mannosidase by hydrazinolysis, and were fractionated into at least 15 homogeneous oligosaccharides. Most of them are oligosaccharides with galactose and N acetylglucosamine residues attached to a common core, alpha Man2 beta Man beta GlcNAc(+/- alpha-L-Fuc)beta GlcNAc. About 50% of the oligosaccharides contain one or two outer chains composed of one beta-linked N-acetylglucosamine and two beta linked galactose residues attached to the core portions, and the others seem to be metabolic intermediates. Based on the results of studies on the binding of alpha-mannosidase to RCA (Ricinus communis agglutinin) I-agarose and MBP (mannan binding protein)-Sepharose, which are specific for glycoproteins possessing N acetyllactosamine-type and oligomannoside-type (including oligomannosides with N acetylglucosamine at the reducing termini) oligosaccharides, respectively, about 85% of the enzyme molecules were found to have both types of oligosaccharides. Similarly, it was shown that of the several acid hydrolases present in the lysosomes purified from rat liver, only alpha-mannosidase has both types of oligosaccharides, and the greater parts of beta-glucuronidase, acid phosphatase and beta-N-acetylhexosaminidase seem to have only oligomannoside-type oligosaccharides. PMID- 3096981 TI - Modulation by phospholipids of the activity of monoamine oxidase purified from pig liver. AB - Monoamine oxidase was purified from pig liver mitochondria to homogeneity. The enzyme sample contained a large amount of phospholipids. Depletion of lipids from the enzyme sample resulted in a decrease in its activity, while activity was restored by the binding of the lipid-depleted enzyme to phosphatidylcholine, phosphatidylethanolamine, or mitochondrial lipids. Upon binding the lipid depleted enzyme to the mixture of phosphatidylcholine and phosphatidylethanolamine (molar ratio, 1 : 1), the enzymatic activity toward serotonin was elevated over that of the purified enzyme, but not toward benzylamine, suggesting a change in substrate specificity. Upon lipid depletion, inhibition by deprenyl became weaker, while that by clorgyline became stronger. This alteration was reversed by the binding to lipids. By the binding of the lipid-depleted enzyme to some lipids such as the mixture of phosphatidylcholine and phosphatidylethanolamine (molar ratio, 1 : 1), inhibition by clorgyline became even weaker than for the original enzyme sample. PMID- 3096982 TI - Cloning and nucleotide sequence of the aspartase gene of Pseudomonas fluorescens. AB - The aspartase gene (aspA) of Pseudomonas fluorescens was cloned and the nucleotide sequence of the 2,066-base-pair DNA fragment containing the aspA gene was determined. The amino acid sequence of the protein deduced from the nucleotide sequence was confirmed by N- and C-terminal sequence analysis of the purified enzyme protein. The deduced amino acid composition also fitted the previous amino acid analysis results well (Takagi et al. (1984) J. Biochem. 96, 545-552). These results indicate that aspartase of P. fluorescens consists of four identical subunits with a molecular weight of 50,859, composed of 472 amino acid residues. The coding sequence of the gene was preceded by a potential Shine Dalgarno sequence and by a few promoter-like structures. Following the stop codon there was a structure which is reminiscent of the Escherichia coli rho independent terminator. The G + C content of the coding sequence was found to be 62.3%. Inspection of the codon usage for the aspA gene revealed as high as 80.0% preference for G or C at the third codon position. The deduced amino acid sequence was 56.3% homologous with that of the enzyme of E. coli W (Takagi et al. (1985) Nucl. Acids Res. 13, 2063-2074). Cys-140 and Cys-430 of the E. coli enzyme, which had been assigned as functionally essential (Ida & Tokushige (1985) J. Biochem. 98, 793-797), were substituted by Ala-140 and Ala-431, respectively, in the P. fluorescens enzyme. PMID- 3096983 TI - Purification and properties of GM1 ganglioside beta-galactosidases from bovine brain. AB - Two GM1-beta-galactosidases, beta-galactosidases I, and II, have been highly purified from bovine brain by procedures including acetone and butanol treatments, and chromatographies on Con A-Sepharose, PATG-Sepharose, and Sephadex G-200. beta-Galactosidase I was purified 30,000-fold and beta-galactosidase II 19,000-fold. Both enzymes appeared to be homogeneous, as judged from the results of polyacrylamide disc gel electrophoresis. Enzyme I had a molecular weight of 600,000-700,000 and enzyme II one of 68,000, as determined on gel filtration. On sodium dodecyl sulfate polyacrylamide slab gel electrophoresis under denaturing conditions, enzyme II gave a single band with a molecular weight of 62,000, while enzyme I gave two minor bands with molecular weights of 32,000 and 20,000 in addition to the major band at 62,000. Both enzymes liberated the terminal galactose from GM1 ganglioside and lactosylceramide but not from galactosylceramide. Enzyme I showed a pH optimum of 4.0 and was heat stable, while enzyme II showed a pH optimum of 5.0 and lost 50% of its activity in 15 min at 45 degrees C. Enzyme I showed a pI of 4.2 and enzyme II one of 5.9. PMID- 3096984 TI - Substrate specificity of endo-beta-galactosidases from Flavobacterium keratolyticus and Escherichia freundii is different from that of Pseudomonas sp. AB - The substrate specificity of endo-beta-galactosidase of Pseudomonas sp. was found to differ from that of Flavobacterium keratolyticus or Escherichia freundii, based on the following experimental results. The endo-beta-galactosidases from these three bacteria released 6-O-sulfo-GlcNAc beta 1-3Gal as one of the major products from keratan sulfates from different sources. In addition to the sulfated disaccharide, Flavobacterium and Escherichia enzymes produced GlcNAc beta 1-3Gal, which is also an integral repeating unit of keratan sulfate, whereas the Pseudomonas enzyme did not release any non-sulfated disaccharide. Tetrasaccharides were prepared from the teleost skin keratan sulfate by digestion with Pseudomonas enzyme followed by gel filtration on Sephadex G-50 chromatography. A part of the tetrasaccharide fraction was hydrolyzed by Flavobacterium enzyme to produce 6-O-sulfo-GlcNAc beta 1-3Gal and GlcNAc beta 1 3Gal, whereas the fraction was completely resistant to retreatment with the Pseudomonas enzyme. Endo-beta-galactosidases from F. keratolyticus and E. freundii hydrolyzed the internal beta-1,4-galactosyl linkage of various neolacto type glycosphingolipids to produce glucosylceramides. However, these glycosphingolipids were completely resistant to the Pseudomonas enzyme. These findings clearly show that the sulfation on the N-acetylglucosamine adjacent to galactose in the lactosaminoglycans is essential for expression of the Pseudomonas enzyme, but not for that of the Flavobacterium or Escherichia enzyme. PMID- 3096985 TI - Identification of the binding site for plasma prekallikrein in human high molecular weight kininogen. A region from residues 185 to 224 of the kininogen light chain retains full binding activity. AB - We studied the ability of fragments of the light chain of human high molecular weight kininogen to bind to plasma prekallikrein. In a competitive fluorescence polarization assay, kallikrein-cleaved light chain (light chain-2; residues 49 255), a cyanogen bromide fragment (residues 185-242), and a tryptic peptide (T-7; residues 185-224) had binding affinities of approximately 20 nM, equivalent to the value for the intact light chain (residues 1-255) of high-molecular-weight kininogen. In contrast, fragments consisting of residues 49-184 and 243-255 showed no binding activity (Kd much greater than 1,000 nM). Direct titrations of fluorescein-labeled derivatives of light chain-2 and peptide T-7 with prekallikrein confirmed that T-7 retained full binding activity for prekallikrein (Kd = 12 +/- 2 nM for labeled light chain-2; Kd = 7 +/- 1 nM for labeled T-7). These results localize the binding site of high molecular weight kininogen for prekallikrein within a region of 40 amino acids (residues 185-224) that resides in the near carboxyl terminus of the light chain of kininogen. PMID- 3096986 TI - Stimulation of prostaglandin E2 synthesis in cloned osteoblastic cells of mouse (MC3T3-E1) by epidermal growth factor. AB - Prostaglandin (PG) E2, known as a bone-resorption factor, was released as a predominant arachidonate metabolite in the culture medium of an osteoblastic cell line cloned from mouse calvaria (MC3T3-E1). Epidermal growth factor (EGF) (10 ng/ml) prominently enhanced endogenous PGE2 synthesis, requiring the simultaneous presence of unidentified factor(s) contained in bovine serum. PGE2 synthesis increased after a lag phase for 1-2 h and reached a maximum level at about 3 h after EGF addition. EGF-stimulated PGE2 synthesis was almost completely blocked by 10 microM cycloheximide or 1 microM actinomycin D. Furthermore, when the cells were pretreated with EGF, the microsomes exhibited an increased activity of fatty acid cyclooxygenase (arachidonic acid----PGH2), whereas the activity of PGE synthase (PGH2----PGE2) remained unchanged. These results suggested an EGF mediated induction of cyclooxygenase. Following increased PGE2 synthesis, DNA synthesis increased and alkaline phosphatase activity decreased in a slower response to EGF. PGE2 (above 0.1 microM) added to the cells could replace EGF. However, such effects of EGF on the osteoblasts could not be attributed totally to an autocrine function of PGE2 produced by stimulation with EGF because these effects of EGF were not abolished by indomethacin, which blocked the PGE2 synthesis. PMID- 3096987 TI - Protein kinase C activation by cis-fatty acid in the absence of Ca2+ and phospholipids. AB - Protein kinase C has been shown to be a phospholipid/Ca2+-dependent enzyme activated by diacylglycerol (Nishizuka, Y. (1984) Nature 308, 693-697; Nishizuka, Y. (1984) Science 225, 1365-1370). We have reported that unsaturated fatty acids (oleic acid and arachidonic acid) can activate protein kinase C independently of Ca2+ and phospholipid (Murakami, K., and Routtenberg, A. (1985) FEBS Lett. 192, 189-193). This study shows that other cis-fatty acids such as linoleic acid also fully activate protein kinase C in the same manner. None of the saturated fatty acids (C:4 to C:18) nor the detergents (sodium dodecyl sulfate and Triton X-100) tested here were as effective as oleic acid. Unlike oleic acid, these detergents strongly inhibited protein kinase C activity induced by Ca2+/phosphatidylserine (PS) and diacylglycerol. Lowering the critical micelle concentration of oleic acid by increasing ionic strength also strongly inhibited oleic acid activation of protein kinase C activity. Dioleoylphosphatidylserine activated protein kinase C effectively (Ka = 7.2 microM). On the other hand, dimyristoylphosphatidylserine, which contains saturated fatty acids at both acyl positions, failed to activate protein kinase C even in the presence of Ca2+. These observations suggest that: protein kinase C activation by free fatty acid is specific to the cis-form and is not due to their detergent-like action, cis fatty acid activation is due to the direct interaction of protein kinase C with the monomeric form of cis-fatty acids and not with the micelles of fatty acids, and cis-fatty acids at acyl positions in PS are also important for Ca2+/PS activation of protein kinase C. PMID- 3096989 TI - The crystallographically determined structures of atypical strained disulfides engineered into subtilisin. AB - The geometries of two disulfide bridges genetically engineered into subtilisin have been characterized by x-ray crystallography to determine the structural and energetic constraints involved in introducing disulfide bonds into proteins. Both disulfide bridges (Cys-24-Cys-87 and Cys-22-Cys-87) exhibit atypical sets of dihedral angles compared to those for other reported disulfide structures in proteins. The geometric trends for naturally occurring disulfides in protein crystal structures are examined. Comparison of the disulfide-containing mutant protein structures with the wild-type structure shows that, in both cases, disulfide incorporation is accommodated by relatively minor changes in local main chain conformation. The Cys-22-Cys-87 disulfide has two high energy dihedral angles (X2 = 121 degrees, X2' = 143 degrees). Both disulfides produce short non bonded contacts with the main-chain. PMID- 3096988 TI - Receptor-mediated endocytosis of interleukin 2 in a human tumor T cell line. Degradation of interleukin 2 and evidence for the absence of recycling of interleukin receptors. AB - We have previously described a human tumor T cell line, IARC 301, which constitutively expresses biologically functional interleukin 2 (IL2) receptors. The fate of IL2 after binding to surface high affinity receptors was investigated. After a few minutes, IL2 is internalized at 37 degrees C and is subsequently degraded and released in the medium. The half-life for surface high affinity IL2 receptors, as measured in the presence of cycloheximide, is about 1 h and does not depend upon the presence of IL2. After trypsin digestion of cell surface high affinity receptors in the absence of protein biosynthesis, we could not detect any receptor reappearance on the cell membrane, whether IL2 was added or not. Taken together these results show that IL2 receptors are constantly internalized in these cells in the presence or absence of IL2 and that they do not recycle to the plasma membrane after receptor-mediated endocytosis. PMID- 3096990 TI - The involvement of carboxylate groups of putidaredoxin in the reaction with putidaredoxin reductase. AB - Modification of carboxyl groups on putidaredoxin with 1-ethyl-3-[3 dimethylaminopropyl]carbodiimide (EDC) resulted in loss of putidaredoxin reductase activity. The modification did not affect the visible absorption spectrum of putidaredoxin, indicating that the iron-sulfur center was not perturbed. In order to identify the carboxyl groups labeled by EDC, native and EDC-treated putidaredoxin were digested with a combination of trypsin and Staphylococcus aureus protease, and the resulting peptides were separated by high pressure liquid chromatography. The most heavily modified carboxyl groups were found to be those at residues 58, 65, 67, 72, and 77. These carboxyl groups are located in the same general region of the protein as those on adrenodoxin that have been shown to be involved in binding to both adrenodoxin reductase and cytochrome P-450scc. Chemical modification was also used to compare the role of lysine, arginine, and histidine residues on putidaredoxin and adrenodoxin. Modification of lysine and arginine residues had no effect on the reductase activity of either protein. The reductase activity of adrenodoxin was unaffected by labeling with 1 eq of diethyl pyrocarbonate/histidine residue, but labeling with a second equivalent completely abolished both activity and the iron-sulfur center spectrum. In contrast, modification of the 2 histidines in putidaredoxin with 1 eq each resulted in nearly complete loss of reductase activity. There was no significant activity for adrenodoxin in the putidaredoxin reductase assay or for putidaredoxin in the adrenodoxin reductase assay, demonstrating that, in spite of the structural similarity between the two proteins, they are not interchangeable functionally. PMID- 3096991 TI - Metabolism of platelet-activating factor by arachidonic acid-depleted rat polymorphonuclear leukocytes. AB - 1-O-[3H]Alkyl-2-acetyl-sn-glycero-3-phosphocholine ([3H]PAF) and 1-O-[3H]alkyl-2 lyso-sn-glycero-3-phosphocholine ([3H]lyso-PAF) when incubated with rat polymorphonuclear leukocytes (PMN) were rapidly metabolized to 1-O-[3H]alkyl-2 acyl-sn-glycero-3-phosphocholine ([3H]alkyl-acyl-GPC) containing long chain acyl groups in the sn-2 position. The specificity and the absolute requirements of arachidonate (20:4) for acylation into PAF and lyso-PAF were investigated by comparing the rate of [3H]PAF and [3H]lyso-PAF metabolism by control rat PMN with that by rat PMN depleted of 20:4. Comparable rates of metabolism of [3H]PAF and [3H]lyso-PAF by both control and 20:4-depleted PMN were observed at all the concentrations of PAF and lyso-PAF studied. The nature of the fatty acyl group incorporated into the sn-2 position of the [3H]alkyl-acyl-GPC formed was analyzed by argentation chromatography. Dienoic fatty acids were the major fatty acid incorporated into the alkyl-acyl-GPC by both control and 20:4-depleted PMN at all the incubation times studied. At 3 min of incubation with [3H]PAF and [3H]lyso PAF, control PMN had small but significant amounts of [3H]alkyl-acyl-GPC containing tetraenoic fatty acids, the concentration of which gradually increased as the incubation time progressed. On the other hand, under similar conditions, 20:4-depleted PMN had only trace amounts of the [3H]alkyl-acyl-GPC with tetraenoic fatty acid and the concentration of which remained at the low level throughout the incubation time. At 3 min of incubation, the 20:4-depleted PMN had small but significant amounts of [3H]alkyl-acyl-GPC with saturated fatty acids, the amount of which declined by 10 min and remained at that level as the incubation time progressed. While the concentration of [3H]alkyl-acyl-GPC with dienoic fatty acids in the 20:4-depleted cells gradually increased with the progress of incubation time, these molecular species of GPC in the control PMN remained more or less constant. In spite of a very high concentration (equivalent to that of 20:4 in control PMN) of eicosatrienoic acid (20:3 delta 5,8,11) in the 20:4-depleted PMN, no significant amounts of [3H]alkyl-acyl-GPC with trienoic fatty acid were formed by these cells. The rate of metabolism of [3H]PAF and [3H]lyso-PAF by the resident macrophages isolated from control and 20:4-depleted rats was similar.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3096992 TI - Reconstitution of ATP-dependent calcium transport from streptococci. AB - Membrane vesicles of three streptococcal strains (Streptococcus faecalis, Streptococcus lactis, and Streptococcus sanguis) were extracted with octyl-beta-D glucoside in the presence of Escherichia coli lipid and glycerol. For reconstitution, the detergent extract was mixed with bath-sonicated E. coli lipid, in the presence of octyl-beta-D-glucoside, and proteoliposomes were formed by a 25-fold dilution. ATP-dependent calcium accumulation by proteoliposomes was comparable to that found in parent vesicles. Recovery of this calcium transport activity was dependent on the inclusion of an osmolyte protein stabilant (glycerol, etc.) during solubilization. The properties of ATP-driven calcium transport were studied in the reconstituted system. In proteoliposomes, ATP linked calcium accumulation was not affected by the protonophore, carbonyl cyanide p-trifluoromethoxyphenylhydrazone, or by the ionophores, valinomycin and nigericin, in the presence of potassium, or by N,N'-dicyclohexylcarbodiimide, an inhibitor of the F0F1-ATPase. On the other hand, calcium transport was completely blocked by micromolar levels of orthovanadate; half-maximal inhibitions were observed at 0.4, 4, and 4 microM vanadate, for S. faecalis, S. lactis, and S. sanguis, respectively. This marked sensitivity to orthovanadate suggests operation of an E1E2-type ion-motive pump. These data demonstrate that, in a reconstituted system, calcium transport is not linked to an ATP-dependent proton circulation via the F0F1-ATPase, but rather is driven by a calcium-translocating ATPase. Thus, calcium extrusion from the cytosol of enteric, lactic acid, or oral streptococci is mediated by an ATP-linked process analogous to the ion-motive ATPases of eukaryotic membranes. PMID- 3096993 TI - Cloning and characterization of cDNA encoding 3-methylcholanthrene inducible rat mRNA for UDP-glucuronosyltransferase. AB - We have isolated cDNA clones of the mRNA for rat UDP-glucuronosyltransferase that catalyzes the glucuronidation of 4-nitrophenol, by using synthetic oligonucleotides as hybridization probes. The complete nucleotide sequence of the 1,927-base pairs cDNA insert has been determined. With untranslated sequences of 124 and 216 base pairs in the 5'- and 3'-terminal regions, respectively, the cDNA insert contained 1,587 base pairs that encode a complete primary structure of a putative precursor form of 4-nitrophenol UDP-glucuronosyltransferase with a calculated molecular weight of 60,114. The cDNA sequence also indicates the presence of 25 amino acids preceding the sequence determined by microsequence of the isolated protein. This extrapeptide, for the most part, consists of hydrophobic amino acids which are characteristic of the signal peptides as found for secretory proteins and most transmembrane proteins. Furthermore, the deduced amino acid sequence contains a putative halt transfer signal of a hydrophobic segment (residues 487-510), which is flanked on both sides by the peptide segments of highly charged amino acid residues (residues 463-486 and 511-529). These features are consistent with the properties of transmembrane proteins. Specific cDNA probes were used to analyze the induction of the enzyme in rat tissues by treatment with 3-methylcholanthrene. RNA blot analysis showed that 3 methylcholanthrene increased 10- to 15-fold the amount of hybridizable mRNA in liver. The livers and kidneys from 3-methylcholanthrene-treated rats were found to contain almost the same amount of hybridizable mRNA, although the basal level in the kidney was much higher than that of the liver, and the amounts in the lung were much lower than that of the liver and kidney. PMID- 3096994 TI - Location of long chain fatty acid-binding sites of bovine serum albumin by affinity labeling. AB - Affinity labeling with palmitic acid was used to identify long chain fatty acid binding sites of bovine serum albumin. [1-14C]Palmitic acid was activated by esterification with N-ethyl-5-phenyl-isoxazolium-3'-sulfonate (Woodward's Reagent K). The product was purified by chromatography and shown to compete with unesterified fatty acids for binding sites on bovine serum albumin. Activated [14C]palmitic acid coupled covalently to albumin producing [14C]palmitoyl albumins containing from 0.12 to a maximum of 6.9 mol of attached label per mol of albumin. The presence of the covalently attached affinity label depressed binding of other long chain fatty acids to albumin. Albumin carrying 1 eq. of [14C]palmitate was cleaved using cyanogen bromide, pepsin, and trypsin. Radioactive peptides were isolated by high pressure liquid chromatography. Three peptides accounted for greater than 90% of the label. Residues labeled with [14C]palmitate were identified as Lys-116, Lys-349 and Lys-473, and the relative distribution of label was 10, 45, and 45% respectively, consistent with the presence of two strong binding sites in the COOH-terminal half of albumin and a somewhat weaker site in the NH2-terminal half. PMID- 3096995 TI - Apolipoprotein B mediates the capacity of low density lipoprotein to suppress neutrophil stimulation by particulates. AB - Low density lipoprotein (LDL) inhibits phagocytosis of certain negatively charged particulates and also inhibits subsequent cellular secretory and oxidative responses to these particulates. In the present work, we have defined the structural features of LDL involved in this activity. Starch-heptane extraction depleted greater than 95% of neutral lipids but had little effect on the capacity of LDL to inhibit monosodium urate crystal- or polystyrene latex bead-induced neutrophil chemiluminescence (CL). Liposomes containing gamma-palmitoyl-beta oleoylphosphatidylcholine (PC) with unesterified cholesterol (PC:cholesterol = 2:1), PC and sphingomyelin (PC:sphingomyelin = 2.3:1), or PC alone lacked the capacity to inhibit urate-induced CL. However, incorporation of apoB-100 into liposomes via cholate dialysis rendered them nearly as inhibitory for urate induced neutrophil CL as LDL on a protein weight basis. Moreover, delipidated apoB-100, containing less than 3% residual phospholipid, inhibited neutrophil responses to urate crystals or latex beads (degranulation and superoxide anion release) in a stimulus-specific manner. Modifications of the lysine residues of apoB (e.g. acetylation) reduced both the capacity of LDL to inhibit urate crystal induced CL and to bind to urate crystals. The effects of apoB lysine residue modification were reversible, proportional to the extent of modification, and were not attributable to alteration of the net charge of apoB. Thus, the apoB-100 of LDL both mediates and shares the capacity of native LDL to inhibit certain neutrophil responses to particulates. PMID- 3096996 TI - Apolipoprotein A-IV. A determinant for binding and uptake of high density lipoproteins by rat hepatocytes. AB - To identify the role of a specific apoprotein other than apoE which might be responsible for the receptor-mediated uptake of high density lipoprotein (HDL) by rat hepatocytes, 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) was combined with rat apoE, apoA-I, or apoA-IV to form apoprotein-phospholipid complexes and the complexes were tested for their binding and uptake by primary rat hepatocytes. Apoprotein-POPC complexes were labeled with the specific fluorescent probe, 1,1-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine to monitor their uptake by cultured rat hepatocytes at 37 degrees C using digital fluorescence imaging microscopy or were labeled with 125I to study their binding to hepatocytes at 4 degrees C. POPC, either alone or with apoA-I, was not internalized by rat hepatocytes while complexes containing apoE or apoA-IV were taken up by the cells. Specific binding at 4 degrees C was demonstrated for apoE free HDL, apoA-IV X POPC, and apoE X POPC but not for apoA-I X POPC. The binding of apoE-free HDL was inhibited by apoA-IV X POPC, apoE-free HDL, and apoA-IV + apoA-I X POPC but not by apoA-I X POPC. Binding of apoA-IV X POPC was inhibited by apoE-free HDL, apoA-IV X POPC, and apoA-IV + apoA-I X POPC, but not by apoE X POPC or apoE-enriched HDL. These data indicate that apoA-IV is a ligand responsible for the rat HDL binding to primary rat hepatocytes and that apoA-IV binds to a receptor site distinct from apoE-dependent receptors such as the apoB,E or chylomicron-remnant receptor. PMID- 3096997 TI - Hemopexin is a developmentally regulated, acute-phase plasma protein in the chicken. AB - Identity has been established between chicken hemopexin and alpha 1-globulin "M," a plasma known for the hormone responsiveness of its synthesis in monolayer cultures of embryonic chicken hepatocytes (Grieninger, G., Plant, P. W., Liang, T. J., Kalb, R. G., Amrani, D., Mosesson, M. W., Hertzberg, K. M., and Pindyk, J. (1983) Ann. N. Y. Acad. Sci. 408, 469-489). Identification was based on immunological cross-reactivity, electrophoretic behavior on sodium dodecyl sulfate-polyacrylamide gels, heme-binding capacity, and pattern of cleavage by proteolytic enzymes. Electroimmunoassays were used to investigate plasma protein levels, particularly those of hemopexin, in the acute-phase response and embryonic development. Acute-phase plasma protein production, elicited by injection of chickens with turpentine, bore many similarities to the pattern of hepatocellular plasma protein synthesis produced in response to the addition of specific hormones in culture. The response of the stressed chickens included elevated levels of hemopexin and fibrinogen (5- and 2-fold, respectively) accompanied by a 50% drop in albumin. Hemopexin levels of developing chick embryos were measured for several days before and after hatching. Onset of hemopexin production occurred around the time of hatching, and was followed by a steep increase (more than 1000-fold over 4 days). Similarly, it was not until the 12th h of culture that hepatocytes isolated from both early and late stage chicken embryos began to produce hemopexin, although, from their initiation in culture, they secreted a number of other plasma proteins in quantity. After 12 h, hepatocellular output of hemopexin rapidly accelerated. This precocious induction ex vivo required no hormonal or macromolecular medium supplements. These observations indicate that the embryonic chicken hepatocyte culture system will provide a useful model for studying the regulation of hemopexin biosynthesis in hepatic development and the acute-phase response. PMID- 3096998 TI - Transcription initiation at the Escherichia coli galactose operon promoters in the absence of the normal -35 region sequences. AB - The gal operon regulatory region contains two overlapping promoters, P1 and P2, regulated by cyclic AMP and the cyclic AMP receptor protein (cAMP X CRP). Starting with a mutation that eliminated P1, the promoter that is usually dependent on cAMP X CRP, we constructed a series of deletions that substituted increasing amounts of DNA sequence from upstream of P2, the promoter that usually functions in the absence of cAMP X CRP. Expression from P2 in vivo was halved by deletions that replace the -35 region with unrelated sequences, showing that the 35 sequence participates in promoter function, but is not essential. In vitro studies show that replacement of the -35 sequence increases the time for open complex formation at P2, but does not alter the transcription start point. We examined the effects of the same deletions at the wild type gal promoter region: again, the deletion that replaces the -35 region halves expression in vivo. However, in this case, in the absence of cAMP X CRP, the deletion switches expression from the P2 promoter to P1, the promoter that is usually dependent on cAMP X CRP. Moreover, although the deletion also removes the specific cAMP X CRP binding site, this P1 activity is sharply inhibited in a crp+ background. We argue that this is due to a direct contact between CRP and RNA polymerase bound at the P1 Pribnow box, and we discuss the role of the -35 sequence at these and other promoters. PMID- 3096999 TI - beta-Amino acid transport across the renal brush-border membrane is coupled to both Na and Cl. AB - Sodium-dependent beta-alanine uptake into dog renal brush-border membrane vesicles was studied. Kinetic analysis indicated a single transport system, highly specific for beta-amino acids, with Km = 35 microM at 100 mM NaCl. Sodium dependent beta-alanine transport was markedly anion-dependent, being highest in the presence of chloride (Cl greater than Br greater than SCN greater than NO3 approximately I greater than F) and virtually nonexistent in the presence of gluconate and other nonphysiological chloride substitutes. In addition, it was observed that beta-alanine uptake could be driven against a concentration gradient by a chloride gradient. Similar results were found for sodium. Taken together, these observations provide strong evidence that beta-alanine transport across the renal brush-border membrane is coupled to both sodium and chloride. Studies of the dependence of beta-alanine flux on chloride and sodium concentrations indicated that one chloride ion and multiple sodium ions were involved in the beta-alanine transport event. beta-Alanine flux on chloride found to involve the net transfer of positive charge, consistent with these stoichiometric assignments. The hallucinogen harmaline inhibited beta-alanine uptake in a 1:1 fashion, presumably by acting at a single site on the transport molecule. The ability of harmaline to inhibit beta-alanine uptake was decreased when the chloride concentration was lowered but was unchanged when the sodium concentration was decreased. These results indicate that harmaline does not compete with sodium for a binding site on the carrier as has been suggested for other sodium-coupled transport systems, and that instead, chloride may be required for harmaline binding to the beta-alanine transporter. PMID- 3097000 TI - Control of mitochondrial content of adenine nucleotides by submicromolar calcium concentrations and its relationship to hormonal effects. AB - Rat liver mitochondria were incubated at 30 degrees C with 4 mM ATP in a medium similar in electrolyte composition to that of hepatic cytosol. Under these conditions, a net increase in mitochondrial adenine nucleotides was observed that was dependent on the concentration of free Ca2+ [( Ca2+]) in the incubation medium. At 0.2 microM [Ca2+] or less, there was no demonstrable uptake of adenine nucleotides; at 0.4 microM [Ca2+], or greater, net uptake occurred. The calcium dependent accumulation of nucleotides by mitochondria required Mg2+ in the incubation medium and was insensitive to carboxyatractyloside. The uptake of adenine nucleotides was enhanced by the addition of antimycin A or antimycin A together with oligomycin. Accumulation of nucleotides appeared to be associated with a small increase in mean mitochondrial volume, but the membrane potential was not affected. No uptake or loss of NAD-NADH by mitochondria was detected. Ruthenium red failed to inhibit the calcium-dependent uptake of adenine nucleotides by the mitochondria, indicating that stimulation of this process by Ca2+ does not involve transport of the cation into mitochondria by the Ca2+ uniporter. Because glucagon acts to elevate cytosolic [Ca2+] from approximately 0.2 microM to 0.6 microM, the same range affecting nucleotide uptake, it is proposed that the increase in mitochondrial adenine nucleotides that follows treatment with glucagon is mediated by the rise in cytosolic [Ca2+] produced by the hormone. This hypothesis was supported by the observation that epinephrine and A23187, agents that raise cytosolic [Ca2+], increased the content of mitochondrial adenine nucleotides in isolated hepatocytes. Furthermore, cells, incubated under calcium-depleting conditions, had a diminished response to glucagon. PMID- 3097001 TI - Human apolipoprotein A-I forms thermally stable complexes with anionic but not with zwitterionic phospholipids. AB - The mechanism of the association of human plasma apolipoprotein A-I (apo A-I) with the acidic phospholipids, dimyristoylphosphatidylglycerol (DMPG), egg yolk phosphatidylglycerol, and dioleoylphosphatidylserine as well as with the zwitterionic dimyristoylphosphatidylcholine (DMPC) has been studied using turbidimetry, circular dichroism, high-sensitivity differential scanning calorimetry, and electron microscopy. The association of apo A-I with multilamellar liposomes of acidic phospholipids is rapid over a broad temperature range at and above the temperature of the lipid gel to liquid crystalline transition, Tc. This is in contrast to zwitterionic phosphatidylcholine which recombines with apo A-I only over a narrow temperature range around Tc. The complex of apo A-I with DMPC denatures at elevated temperatures giving rise to a calorimetrically detectable transition. The temperature range and width of this transition is shown to be markedly dependent on the heating rate. This is again in contrast to apo A-I recombinants with DMPG which show no calorimetrically detectable thermal denaturation, at least in a temperature range up to 100 degrees C. Also circular dichroism data indicate high resistance of apo A-I to thermal unfolding in the presence of DMPG. It is concluded that the complexes of apo A-I with DMPC are thermodynamically stable only at temperatures near Tc, whereas above and below this temperature range the stability of these recombinants is determined by kinetic factors. In contrast, complexes of apo A-I with DMPG and other acidic phospholipids may be thermodynamically stable over a wide temperature range greater than or equal to Tc. In spite of these fundamental differences between zwitterionic and acidic phospholipids in their mode of association with apo A-I, the binding affinity and the morphology of the recombinants are similar. Both apo A-I X DMPC and apo A-I X DMPG complexes form lipoprotein particles having a discoidal shape. PMID- 3097002 TI - Crystallization of and preliminary X-ray data for bovine carbonic anhydrase III. AB - Crystals of bovine carbonic anhydrase III have been grown in a solution of polyethylene glycol. The crystals are monoclinic, space group P2(1), with the unit cell parameters a = 50.6 A, b = 44.7 A, c = 56.9 A, and beta = 90.3 degrees. The asymmetric unit contains 1 molecule. The diffraction pattern extends beyond 2.0-A resolution. PMID- 3097003 TI - Biosynthesis of bacterial glycogen. Primary structure of Escherichia coli ADP glucose:alpha-1,4-glucan, 4-glucosyltransferase as deduced from the nucleotide sequence of the glgA gene. AB - The nucleotide sequence of the glgA gene, coding for glycogen synthase (EC 2.4.1.21) was elucidated. It consists of 1431 base pairs specifying a protein of 477 amino acids. The deduced amino acid sequence was consistent with the amino acid analysis obtained with the pure protein as well as with the molecular weight as determined from sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The deduced amino acid sequence was also consistent with the amino-terminal acid sequence and amino acid sequence analysis of various peptides obtained from CNBr degradation of purified glycogen synthase. PMID- 3097004 TI - Tyrosinase isozyme heterogeneity in differentiating B16/C3 melanoma. AB - The B16/C3 murine melanoma is a pigmented tumor that is rich in the copper containing enzyme, tyrosinase. This enzyme, which converts tyrosine to melanin precursors, is largely associated with membrane fractions of cells and exists in a number of discrete isozymic forms ranging in molecular mass from 58,000 to 150,000 daltons and pI from 3.4 to 5.2. One of these isozymes (Mr = 58,000, pI 3.4) has been purified to homogeneity. The purified enzyme catalyzes the hydroxylation of L-tyrosine to L-dihydroxyphenylalanine (L-DOPA) and the conversion of L-DOPA to dopaquinone. Ascorbic acid, tetrahydrofolate, and dopamine can serve as cofactors in the hydroxylase reaction. The Michaelis constants for the purified enzyme were 7 X 10(-4) M for L-tyrosine and 6 X 10(-4) M for L-DOPA. The Vmax for L-DOPA was much greater than the Vmax for L-tyrosine indicating that tyrosine hydroxylation is rate-limiting in melanin precursor biosynthesis. Two putative copper chelators, phenylthiourea and diethyldithiocarbamide inhibited both the tyrosine hydroxylase and L-DOPA oxidase activities of the enzyme. Phenylthiourea was a noncompetitive inhibitor while diethyldithiocarbamide was a competitive inhibitor indicating that these agents act by different mechanisms. When digested with proteases and glycosidases, higher molecular weight forms of tyrosinase co-migrated with the purified enzyme in isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggesting that the isozyme was derived from larger precursors. Thus, post-translational processing of tyrosinase may underlie isozyme diversity and this may be important in the control of melanogenesis in this tumor model. PMID- 3097005 TI - Use of monoclonal antibodies to locate the chondroitin sulfate chain(s) in type IX collagen. AB - Recent results show that type IX collagen isolated from chicken cartilage is associated with one or perhaps two chondroitin sulfate chains. To locate the chondroitin sulfate chain(s) along the type IX collagen molecule, rotary shadowing was performed in the presence of monoclonal antibodies which recognize stubs of chondroitin sulfate generated after chondroitinase ABC digestion. Monoclonal antibodies 9-A-2 and 2-B-6 which recognize stubs of chondroitin 4 sulfate were found to bind specifically to the NC3 domain of type IX collagen, and this binding was dependent on prior digestion of the preparation with chondroitinase ABC. Monoclonal antibody 1-B-5, which recognizes unsulfated stubs of chondroitin sulfate, did not show any specific binding to type IX collagen either with or without chondroitinase ABC digestion. As a control, monoclonal antibody 2C2 was used, which in previous work was shown to bind specifically to an epitope located close to or at the NC2 domain. Binding of this antibody to NC2 was unaffected by chondroitinase ABC digestion, and no specific binding of the antibody to the NC3 domain was detected either before or after chondroitinase ABC digestion. PMID- 3097006 TI - Evidence that two covalent intermediates, phosphoryl and malonyl enzymes, are formed during malonyl-coenzyme A synthetase catalysis. AB - The isolation of malonyl-coenzyme A synthetase from Pseudomonas fluorescens grown on malonate has been reported recently (Kim, Y.S., and Bang, S.K. (1985) J. Biol.Chem. 260, 5098-5104). This enzyme is phosphorylated in the presence of ATP and Mg2+. The phosphoryl group appears on one subunit of the enzyme composed of two different subunits, and the phosphoryl enzyme is acid labile and base stable. The phosphoryl group on the enzyme is released by the incubation of the phosphoryl enzyme with malonate and malonyl enzyme is formed. The malonyl enzyme is acid labile and also relatively unstable under basic conditions. The malonyl group is found on the subunit of the enzyme which is phosphorylated. Malonyl-CoA is formed when malonyl enzyme reacts with coenzyme A. These results suggest that two convalent intermediates, phosphoryl and malonyl enzyme, are sequentially formed in the synthesis of malonyl-coenzyme A by malonyl-coenzyme A synthetase catalysis. PMID- 3097007 TI - Evidence for the interaction between the calcium indicator 1,2-bis(o aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and calcium-binding proteins. AB - Stopped-flow and static difference spectroscopy experiments have shown that the calcium indicator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) interacts with several different calcium-binding proteins (beta-trypsin, parvalbumin, and calmodulin) and with serum albumin under experimental conditions commonly used in biophysical studies. The interaction decreases at high ionic strength. EDTA competes with BAPTA in the interaction with the proteins. PMID- 3097008 TI - Lipoxin A. Stereochemistry and biosynthesis. AB - Lipoxin A (LXA) was prepared by incubation of either (15S)-15-hydroxy-5,8,11-cis 13-trans-eicosatetraenoic acid (15-HETE) or (15S)-15-hydroperoxy-5,8,11-cis-13 trans-eicosatetraenoic (15-HPETE) with human leukocytes stimulated by either the ionophore A23187 or the chemotactic peptide fMet-Leu-Phe. Comparison with four trihydroxyeicosatetraenoic acids prepared by total synthesis showed that biologically derived LXA is 5S,6R,15S)-5,6,15-trihydroxy-7,9,13-trans-11-cis eicosatetraenoic acid. Three isomers of LXA were also identified in extracts of leukocytes utilizing an improved isolation procedure. These were (5S,6S,15S) 5,6,15-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid (6S-LXA), (5S,6R,15S) 5,6,15-trihydroxy-7,9,11,13-trans-eicosatetraenoic acid (11-trans-LXA), and (5S,6S,15S)-5,6,15-trihydroxy-7,9,11,13-trans-eicosatetraenoic acid (6S-11-trans LXA). 18O2-labeling studies indicated that formation of LXA and its isomers occurred with incorporation of 18O at their C-5 but not C-6 positions. These results suggest that 15-hydroxy-5,6-epoxy-7,9,13-trans-11-cis-eicosatetraenoic acid or its equivalent may serve as one intermediate in the biosynthesis of LXA and 6S-LXA. When added to guinea pig lung strips LXA provoked contractions which were slow in onset and long lasting. In addition, dose response studies showed that biologically derived LXA and synthetic LXA were indistinguishable in this bioassay whereas synthetic 6S-LXA and biologically derived 6S-LXA did not share this activity. Taken together, these results suggest that activated leukocytes utilize exogenous 15-HETE to generate lipoxins which in turn can modulate cellular responses. PMID- 3097009 TI - Sulfation of porcine parathyroid secretory protein I. Detection of tyrosine sulfate. AB - Secretory Protein I (SP-I) is an acidic glycoprotein that is stored and co secreted with parathormone by parathyroid glands. It has been found to be chemically similar, if not identical, to chromogranin A of the adrenal medulla and to be present in most endocrine cells. In the present study, 35SO4 was shown to be incorporated into SP-I and several other proteins of porcine parathyroid tissue incubated in vitro. The predominant sulfated species secreted to the medium was SP-I. Up to 20% of the tyrosine residues in secreted SP-I were labeled with 35SO4. Both the cellular and secreted forms migrated on sodium dodecyl sulfate gels as a pair of proteins with apparent molecular weights of 82,000 and 78,000. The 82-kDa protein could be converted to the 78-kDa species by treatment with neuraminidase. Sulfate exists in SP-I as tyrosine sulfate based on the identification of this amino acid by thin layer electrophoresis following alkaline hydrolysis. Extracellular Ca2+ (3 mM) greatly suppressed the secretion of 35SO4-labeled SP-I without affecting the intracellular sulfation of the molecule or the secretion of a minor sulfated protein unrelated to SP-I. The ratio of incorporated 35SO4 to 3H-amino-acid was greater in secreted SP-I than in tissue SP-I, suggesting that much sulfation of this protein occurred during or just before secretion. PMID- 3097010 TI - Interactions of Bacillus subtilis RNA polymerase with subunits determining the specificity of initiation. Sigma and delta peptides can bind simultaneously to core. AB - The Bacillus subtilis RNA polymerase sigma 43 subunit and the phage SP82 encoded 28-kDa peptide are responsible for the binding of RNA polymerase to early and middle SP82 promoters, respectively. The delta peptide enhances the specificity of the interaction of B. subtilis RNA polymerase with these promoters. We have used sedimentation experiments to determine the effect of each of the three specificity factors, delta, sigma, and the 28-kDa peptide, on the binding of the other two factors to RNA polymerase core and the effect of NaCl on these binding equilibria. We show that sigma 43 and the 28-kDa peptide can each bind to RNA polymerase core at the same time as delta. Sigma 43 and the 28-kDa peptide have similar affinities to core at 0.1 M NaCl, but the 28-kDa peptide binds to core delta more strongly than sigma 43. The implications of these findings with respect to the replacement of sigma 43 by the 28-kDa peptide and the mechanism of promoter search by B. subtilis RNA polymerase are discussed. PMID- 3097012 TI - Anchimeric assistance in the intramolecular reaction of glucose-dehydrogenase polyethylene glycol NAD conjugate. AB - Polyethylene glycol-bound derivatives of NAD(P) (PEG-NAD(P)) are water-soluble macromolecular coenzymes used in continuous enzyme reactors. These NAD(P) derivatives have good coenzyme activity for many dehydrogenases, but some enzymes such as glucose dehydrogenase (EC 1.1.1.47) show very low activity with these derivatives (less than 0.1% of that for native NAD(P)). In this work, we prepared a covalently linked glucose-dehydrogenase-polyethylene glycol-NAD conjugate (GlcDH-PEG-NAD) and found that the conjugate shows a much higher reaction rate than that of the native enzyme plus PEG-NAD: the ratio of the reaction rates of GlcDH-PEG-NAD and the native enzyme plus PEG-NAD is calculated to be 10,000-fold at the concentrations of the enzyme subunit and NAD moiety of 0.31 and 0.65 microM, respectively; the rate of the conjugate is even higher than that of the native enzyme plus native NAD. This rate acceleration is due to the increase in the effective concentration of NAD moiety ("anchimeric assistance") and demonstrates the potential of covalent linking for improving the interaction between an enzyme and a coenzyme derivative. PMID- 3097011 TI - The role of formylmethanofuran: tetrahydromethanopterin formyltransferase in methanogenesis from carbon dioxide. AB - Formylmethanofuran: tetrahydromethanopterin formyltransferase was purified to electrophoretic homogeneity from cells of Methanobacterium thermoautotrophicum. The enzyme is a tetramer of similar or identical subunits (Mr = 41,000). The equilibrium favors transfer of the formyl group to tetrahydromethanopterin (H4MPT) at physiological pH. The product of formyl transfer by the purified enzyme was shown by a number of criteria to be 5-formyl-H4MPT, as opposed to 10 formyl-H4MPT or 5,10-methenyl-H4MPT. Reconstitution of a portion of the methanogenic C1 cycle was effected by combining purified formyltransferase, methenyl-H4MPT cyclohydrolase, formylmethanofuran, and H4MPT to give methenyl H4MPT. Additional reconstitution experiments established that the formyltransferase is an essential enzyme for the conversion of carbon dioxide to methane. In conjunction with previously published data (Donnelly, M.I., Escalante Semerena, J.C., Rinehart, K. L., Jr., and Wolfe, R.S. (1985) Arch. Biochem. Biophys. 242, 430-439), these data substantiate the role of 5-formyl-H4MPT as an intermediate of methanogenesis. PMID- 3097013 TI - Suppression of synthesis of pro-alpha 1(I) and production of altered pro-alpha 2(I) procollagen subunits in 4-nitroquinoline-1-oxide-transformed fibroblasts. AB - The collagen phenotype of a 4-nitroquinoline-1-oxide-transformed line of Syrian hamster embryo fibroblasts, NQT-SHE, was markedly altered from that of normal Syrian hamster embryo cells, which synthesized mainly type I procollagen [pro alpha 1(I)]2 pro-alpha 2(I). Total collagen synthesis in the transformant was reduced to about 30% of the control level primarily because synthesis of the pro alpha 1(I) subunit was completely suppressed. The major collagenous products synthesized consisted of two polypeptides, designated as N-33 and N-50, which could be completely separated by precipitation with ammonium sulfate at 33 and 50% saturation, respectively. N-33 migrated similarly to pro-alpha 2(I) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and N-50 migrated slightly more slowly. The collagenous regions of these chains were more sensitive to protease than the analogous region of procollagen I, but alpha-chains could be obtained by digestion for 2 h at 4 degrees C with high ratios of protein:pepsin. Staphylococcus V8 protease and cyanogen bromide peptide maps of N-33 alpha and N 50 alpha chains indicated that the chains were homologous with, but different than, alpha 2(I) chains and that they differed from each other. Considering their similarity to pro-alpha 2(I), it was surprising to find that the N-collagens were secreted to the same extent as was type I procollagen from Syrian hamster embryo cells and that there were no disulfide bonds between N-collagen chains. Intrachain disulfides were present. One possible explanation for the unusual collagen phenotype of NQT-SHE cells is that transformation induced one or more mutations in the pro-alpha 2(I) structural gene while suppression of synthesis of the pro-alpha 1(I) subunit may be due to a mutation in the regulatory region of its gene or in a general regulatory gene. PMID- 3097014 TI - A Drosophila heat shock locus with a rapidly diverging sequence but a conserved structure. AB - Cytological studies have shown that the heat shock loci 93D of Drosophila melanogaster and 2-48B of Drosophila hydei have several characteristics which suggest that they are homologous loci, yet sequence homology is barely detectable by cross-hybridization. Using cloned DNA sequences we have compared the two loci. Both loci produce transcripts of similar size and number. We have characterized the three predominant transcripts. In each species all three transcripts start at or about the same place within the unique portion of the gene. The longest transcript (approximately 9-10 kilobases) continues through several kilobases of short tandem repeats. The two shorter (1.9 and 1.2 kilobases) transcripts terminate 5' to the repeats. The repeat sequences are strongly conserved within a species but between species they have diverged both in length and in sequence. The longest homology is 9 nucleotides. The unique portions have also diverged significantly but do have some regions of conserved sequence. In both species the cytoplasmic transcript is spliced and polyadenylated but does not appear to contain a significant open reading frame. Thus, although the sequence of this locus has diverged significantly there are conserved features which suggest that the function of the locus is also conserved. PMID- 3097015 TI - Role of ascorbic acid in dopamine beta-hydroxylation. The endogenous enzyme cofactor and putative electron donor for cofactor regeneration. AB - The role(s) of ascorbic acid in dopamine beta-hydroxylation was studied in primary cultures of bovine adrenomedullary chromaffin cells and in isolated bovine adrenomedullary chromaffin vesicles. Dopamine beta-hydroxylase activity was assessed by measuring the rate of conversion of tyramine to octopamine. The ascorbic acid content of chromaffin cells declined with time in culture and the dopamine beta-hydroxylase activity of ascorbate-depleted cells was low. Ascorbate additions to ascorbate-depleted cells increased both the intracellular ascorbate concentrations and the rates of dopamine beta-hydroxylation. Ascorbate uptake into the cells was rapid; however, the onset of enhanced octopamine synthesis by added ascorbate was delayed by several hours and closely followed the time course for accumulation of the newly taken up ascorbate into the chromaffin vesicle. The amount of octopamine synthesized by the chromaffin cells exceeded the intracellular ascorbate content and ascorbate levels were maintained during dopamine beta-hydroxylation in the absence of external ascorbate. This suggests an efficient recycling of ascorbate. In contrast to intact cells, ascorbic acid was depleted during octopamine synthesis in isolated chromaffin vesicles. The molar ratio of octopamine formed to ascorbate depleted was close to unity. Thus, the recycling of intravesicular ascorbate depends on an extravesicular factor(s). The depletion of intravesicular ascorbate during dopamine beta-hydroxylation was prevented by the addition of nonpermeant extravesicular electron donors such as ascorbate or glucoascorbate. This suggests that intravesicular ascorbate is maintained in the reduced state by electron transport across the vesicle membrane. These results are compatible with the hypothesis that both intra- and extravesicular ascorbate participate in the regulation of dopamine beta hydroxylase. Intravesicular ascorbate is the cofactor for the enzyme. Cytosolic ascorbate is most likely the electron donor for the vesicle-membrane electron transport system which maintains the intravesicular cofactor concentration. PMID- 3097016 TI - Liver isozyme of rabbit glycogen synthase. Amino acid sequences surrounding phosphorylation sites recognized by cyclic AMP-dependent protein kinase. AB - Glycogen synthase, the rate-limiting enzyme in glycogen biosynthesis, has been postulated to exist as isozymes in rabbit liver and muscle (Camici, M., Ahmad, Z., DePaoli-Roach, A. A., and Roach, P. J. (1984) J. Biol. Chem. 259, 2466-2473). Both isozymes share a number of properties including multiple phosphorylation of the enzyme subunit. In the present study, we determined the amino acid sequences surrounding phosphorylation sites in the rabbit liver isozyme recognized by cyclic AMP-dependent protein kinase. Two dominant phosphopeptides (P-1 and P-2) were generated from tryptic digestion. Amino acid sequences of the purified peptides were determined by automated Edman degradation using a gas-phase sequenator. The locations of phosphorylated residues were identified by measuring 32Pi release during Edman degradation cycles. The NH2-terminal sequence of peptide P-1 is S-L-S(P)-V-T-S-L-G-G-L-P-Q-W-E-V-E-E-L-P-V-D-D-L-L-L-P-E-V. This sequence exhibits a strong homology to the site 2 region in the NH2 terminus of the muscle isozyme. The NH2-terminal sequence of peptide P-2 is M-Y-P-R-P-S(P) S(P)-V-P-P-S-P-L-G-S-Q-A. This sequence shows strong homology to the site 3 region in the COOH terminus of the muscle isozyme. However, some interesting sequence differences were revealed in this region. For example, substitution of serine for alanine at position 6 of peptide P-2 created a new phosphorylation site for cyclic AMP-dependent protein kinase. Phosphorylation of the proline/serine-rich site 3 region correlated with inactivation of the liver isozyme and suggests an important role for this segment of the molecule in the regulation of glycogen synthase. No phosphorylation sites corresponding to sites 1a and 1b of the muscle isozyme were detected. In addition, the results provide definitive chemical proof that glycogen synthase from rabbit liver and muscle are isozymes encoded by distinct messages. PMID- 3097017 TI - Sizes of Mn-binding sites in spinach thylakoids. AB - The sizes of the Mn-binding sites in spinach thylakoids were estimated by target size analysis, assaying the membrane-bound Mn that was resistant to EDTA washing after radiation inactivation. The inactivation curve showed well the inactivation of two independent Mn-binding sites of different sizes: about two-thirds of the Mn coordinated to a binding site of 65 kDa, and the rest bound to a much smaller site of only about 3 kDa. In the large site, there was about 1 g atom of Mn/110 mol of chlorophyll in spinach thylakoids, which was constant in normally grown plants, although the Mn level in the small site depended on culture conditions. Thylakoids that had been incubated with hydroxylamine or in 0.8 M Tris lost Mn exclusively from the large binding site. PMID- 3097018 TI - Oxidative inactivation of the enzyme rhodanese by reduced nicotinamide adenine dinucleotide. AB - The enzyme rhodanese (thiosulfate sulfurtransferase; EC 2.8.1.1) is inactivated with a half-time of approximately 3 min when incubated with 50 mM NADH. NAD+, however, has virtually no effect on the activity. Inactivation can be prevented by the inclusion of the substrate thiosulfate. The concentration of thiosulfate giving half-protection is 0.038 mM. In addition, NADH, but not NAD+, is a competitive inhibitor with respect to thiosulfate in the catalyzed reaction (Ki = 8.3 mM). Fluorescence studies are consistent with a time-dependent oxidation of NADH in the presence of rhodanese. The sulfur-free form of rhodanese is more rapidly inactivated than the sulfur-containing form. Spectrophotometric titrations show that inactivation is accompanied by the loss of two free SH groups per enzyme molecule. Inactivation is prevented by the exclusion of air and the inclusion of EDTA (1 mM), and the enzyme activity can be largely protected by incubation with superoxide dismutase or catalase. Rhodanese, inactivated with NADH, can be reactivated by incubation with the substrate thiosulfate (75 mM) for 48 h or more rapidly, but only partially, by incubating with 180 mM dithiothreitol. It is concluded that, in the presence of rhodanese, NADH can be oxidized by molecular oxygen and produce intermediates of oxygen reduction, such as superoxide and/or hydrogen peroxide, that can inactivate the enzyme with consequent formation of an intraprotein disulfide. In addition, NADH, but not NAD+, can reversibly bind to the active site region in competition with thiosulfate. These data are of interest in view of x-ray studies that show structural similarities between rhodanese and nucleotide binding proteins. PMID- 3097019 TI - Stereospecific induction of starfish oocyte maturation by (8R) hydroxyeicosatetraenoic acid. AB - Oocyte maturation (meiosis reinitiation) in starfish is induced by the natural hormone 1-methyladenine. This induction of meiotic divisions can be triggered also by four fatty acids: 5,8,11-20:3; 5,8,11,14-20:4 (arachidonic acid); 6,9,12,15-20:4; 5,8,11,14,17-20:5, all other fatty acids being completely inactive. This maturation triggered by eicosanoids occurs in the micromolar range and is facilitated by the presence of calcium. A variety of arachidonic acid derivatives (esters, epoxides, etc.) and metabolites (cyclooxygenase and lipoxygenase products) has been tested; the biological activity is restricted to 8-hydroxyeicosatetraenoic acid (8-HETE), other mono- and poly-HETEs being completely inactive. Maturation triggered by 8-HETE occurs around 10 nM and is insensitive to the presence of calcium. 8-HETE methyl ester and 8 hydroperoxyeicosatetraenoic acid are able to induce maturation at higher concentrations. Both (8S) and (8R) stereoisomers have been tested; the biological activity is strictly restricted to the (8R) isomer. 8-HETE triggers a complete maturation, i.e. maturation-promoting factor appearance, germinal vesicle breakdown, emission of the polar bodies, and formation of a female pronucleus. (8R)-HETE, but not (8S)-HETE, triggers the typical decrease in cyclic AMP concentration induced by 1-methyladenine and the burst of protein phosphorylation associated with maturation. Starfish oocytes oxidize exogenous arachidonic acid into 8-HETE and other HETEs. 8-HETE was identified, after high pressure liquid chromatography purification, by gas chromatography mass spectrometry. Furthermore, it was found that the starfish oocytes only produce the (8R)-HETE isomer. This highly stereospecific induction of oocyte maturation by (8R)-HETE suggests that this fatty acid, or a very closely related fatty acid, may play a role in the transduction of the 1-methyladenine message at the plasma membrane level. PMID- 3097020 TI - Thermodynamics of the binding of AMP to glycogen phosphorylase a. AB - The binding of AMP to rabbit muscle glycogen phosphorylase a (EC 2.4.1.1.) has been studied by equilibrium dialysis and isothermal microcalorimetry at pH 6.9 over a temperature range of 25 degrees C to 35 degrees C. Thermal titration experiments were carried out in various buffer systems. We have found by these methods that a certain number of protons are released when the protein binds to the ligand and are taken up by the buffer. The tetramer of phosphorylase a has been shown to have four equal and independent, non-cooperative binding sites for AMP at 25 degrees C, 30 degrees C, and 35 degrees C; these sites can be assigned to the so-called nucleotide or, activator, sites in the protein. The binding constants together with the changes in Gibbs energy, enthalpy, and entropy per site for the AMP binding were calculated at each temperature. A negative delta Cp value of -2.3 +/- 0.2 J K-1 (AMP bound)-1 was obtained for this binding process. The hydrophobic and vibrational contributions of the heat capacity and entropy changes have been resolved by the method described by Sturtevant (Sturtevant, J. M. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 2236-2240). From this analysis, it appears that the binding is, in all cases, enthalpy-driven, the two entropic contributions, hydrophobic and vibrational, having opposing effects. PMID- 3097021 TI - Purification and characterization of a novel low molecular weight form of single chain urokinase-type plasminogen activator. AB - A low Mr form (Mr 32,000) of single-chain urokinase-type plasminogen activator (scu-PA) was isolated from conditioned culture medium of a human lung adenocarcinoma cell line, CALU-3 (ATCC, HTB-55). The purified material (scu-PA 32k) consists of a single polypeptide chain and is immunologically similar to Mr 33,000 urokinase. Its NH2-terminal sequence is identical to that beginning at Leu 144 of Mr 54,000 urokinase. Whereas low Mr urokinase is derived from mature Mr 54,000 scu-PA by limited hydrolysis by plasmin first of the Lys-158-Ile-159 peptide bond and then of the Lys-136-Lys-137, scu-PA-32k is generated by specific hydrolysis of the Glu-143-Leu-144 peptide bond by an unidentified protease. scu PA-32k resembles its Mr 54,000 scu-PA counterpart by its very low activity on chromogenic substrates for urokinase, by plasminogen-dependent fibrinolytic activity on fibrin plates, and by the lack of specific binding to fibrin. It activates plasminogen directly with high affinity, Km = 0.9 microM, but low turnover number, kcat = 0.0028 s-1. It is converted to fully active two-chain urokinase by plasmin with Km = 12 microM and kcat = 0.3 s-1. Like Mr 54,000 scu PA, it causes significant lysis of a 125I-labeled fibrin clot in human plasma with relatively less fibrinogen breakdown as compared to urokinase. scu-PA-32k, which also has conserved fibrin specificity, represents a molecular variant which may be more suitable for large scale production as a fibrin-specific thrombolytic agent by recombinant DNA technology. PMID- 3097022 TI - Histopathologic evaluation following chronic implantation of chromium and steel based metal alloys in the rabbit central nervous system. AB - Histopathologic evaluation of three metal alloys for chronic implantation in the central nervous system (CNS) was undertaken in rabbits. Throughout the 8 month evaluation period the inflammatory response to the alloys was bland. Two of the alloys tested (chromium based MP35N, Trademark of the Standard Pressed Steel Company, and a stainless steel alloy, BG42 VacArc, Trademark of Latrobe Steel) appeared suitable as CNS implants. The third alloy (stainless steel 440C, Carpenter Steel Company) showed more corrosion than the other alloys, and may be less suitable for implantation. While E. cuniculi infection was found in four rabbits, the infection did not directly interfere with the assessment of the histologic changes directly due to the implants. Autoantibodies to a brain constituent were not observed. PMID- 3097023 TI - The prevention of heterotopic ossification in high-risk patients by low-dose radiation therapy after total hip arthroplasty. AB - A prospective study was done to evaluate the efficacy of treatment with 1,000 rads of radiation in the prevention of heterotopic ossification after total hip arthroplasty in patients who are at high risk. In a previous prospective study, patients who were at high risk for heterotopic ossification after total hip arthroplasty were identified and an effective regimen for its prevention was established. It was demonstrated that treatment with 2,000 rads of radiation that was initiated within four days after the total hip arthroplasty was highly effective in the prevention of heterotopic ossification and in the prevention of recurrence after resection of existing ossification. In the present study, 1,000 rads of radiation was administered in increments of 200 rads over a period of five to seven days and was as effective as treatment with 2,000 rads. The protocol of 1,000 rads is preferable because it reduces the risk of malignancy and the duration of hospitalization. PMID- 3097024 TI - DNA adducts of medicinal drugs: some selected examples. AB - A few selected medicinal drugs, diamminedichloroplatinum (II) compounds, mitomycin C, psoralens, and diethylstilbestrol are briefly reviewed with respect to the formation and biological significance of their DNA adducts. Different types of adducts, e.g., DNA intrastrand crosslinks, DNA interstrand crosslinks, or monoadducts appear to represent the critical DNA lesions of the different drugs, accounting for cytotoxicity and carcinogenicity. Thus, these examples serve to illustrate the complexity of DNA adduct formation and its biological sequelae. PMID- 3097025 TI - The difference in pharmacokinetics of mitomycin C, given either as a single agent or as a part of combination chemotherapy. AB - In a previous report it was suggested that the total body clearance of mitomycin C (MMC) was different after single agent treatment compared to combination chemotherapy. This suggestion was based on recalculations to one dose level. In the present study a fixed dose of 10 mg/m2 was used. Seven patients on single agent MMC and eight on combination chemotherapy were studied. Terminal half-life varied from 25 to 78 mm, volume of distribution from 7 to 73 l/m2, total body clearance from 11 to 56 l/h per m2, and area under the plasma concentration-time curve (AUC) from 177 to 933 micrograms/h per l. Total body clearance was significantly higher and AUC significantly lower in patients on combination chemotherapy. The cause of this difference was not investigated. PMID- 3097026 TI - In vitro transport of a fluorescent nuclear protein and exclusion of non-nuclear proteins. AB - An in vitro system was developed that provides a quick microscopic assay for nuclear transport. The assay uses an extract of Xenopus eggs, normal or synthetic nuclei, and a fluorescently labeled nuclear protein, nucleoplasmin. This in vitro system accurately mimics in vivo nuclear transport, both in exclusivity and in the amount of accumulation observed (up to 17-fold). Selective accumulation of fluorescent nucleoplasmin is observed microscopically within 30 min with rat liver nuclei, Xenopus embryonic nuclei, regrown Xenopus sperm nuclei, or nuclei reconstituted in vitro from bacteriophage lambda DNA. This transport requires the signal domain of nucleoplasmin. Furthermore, the ability of nuclei to accumulate nucleoplasmin directly correlates with their ability to exclude the fluorescent non-nuclear proteins, FITC-immunoglobulin and phycoerythrin. An active transport model would predict that nuclear transport be temperature- and energy-dependent and that inhibition of transport by either low temperature or energy depletion would be reversible. Both predictions were confirmed in our system. Nucleoplasmin accumulation increases with temperature, while the protein is completely excluded at 0 degrees C. The effects of low temperature are reversible. As found for 125I labeled nucleoplasmin (Newmeyer, D. D., J. M. Lucocq, T. R. Burglin, and E. M. De Robertis, 1986, EMBO (Eur. Mol. Biol. Organ.) J., 5:501-510), transport of fluorescent nucleoplasmin is inhibited by ATP depletion. This effect is reversed by later ATP addition. Under ATP-depleted conditions non-nuclear proteins continue to be excluded. These results argue for a direct role of ATP in transport rather than for a simple role in preserving envelope integrity. In a first step towards defining the minimum requirements for a transport medium, egg extracts were depleted of membrane vesicles. Membrane-depleted extracts neither support transport nor maintain the integrity of the nuclear envelope. PMID- 3097027 TI - Calcium ionophore A23187 as a regulator of gene expression in mammalian cells. AB - The calcium ionophore A23187 can reversibly induce the expression of two glucose regulated genes, p3C5 and p4A3. This induction requires a continuous presence of the ionophore for over 2 h. Although extracellular Ca2+ is important for the optimal effect of A23187, it is not necessary for the induction, since a similar response with a lower magnitude can be triggered in cells cultured in low Ca2+ medium buffered with EGTA. Both the basal and induced levels of p3C5 and p4A3 transcripts can be modulated by the calmodulin antagonist W-7, indicating the involvement of Ca2+/calmodulin-associated pathways. In addition, the sensitivity of the A23187 induction to cycloheximide suggests that the induction process is dependent on de novo protein synthesis. PMID- 3097028 TI - Formation of a functional ribosome-membrane junction during translocation requires the participation of a GTP-binding protein. AB - The requirement for ribonucleotides and ribonucleotide hydrolysis was examined at several distinct points during translocation of a secretory protein across the endoplasmic reticulum. We monitored binding of in vitro-assembled polysomes to microsomal membranes after removal of ATP and GTP. Ribonucleotides were not required for the initial low salt-insensitive attachment of the ribosome to the membrane. However, without ribonucleotides the nascent secretory chains were sensitive to protease digestion and were readily extracted from the membrane with either EDTA or 0.5 M KOAc. In contrast, nascent chains resisted extraction with either EDTA or 0.5 M KOAc and were insensitive to protease digestion after addition of GTP or nonhydrolyzable GTP analogues. Translocation of the nascent secretory polypeptide was detected only when ribosome binding was conducted in the presence of GTP. Thus, translocation-competent binding of the ribosome to the membrane requires the participation of a novel GTP-binding protein in addition to the signal recognition particle and the signal recognition particle receptor. The second event we examined was translocation and processing of a truncated secretory polypeptide. Membrane-bound polysomes bearing an 86-residue nascent chain were generated by translation of a truncated preprolactin mRNA. Ribonucleotide-independent translocation of the polypeptide was detected by cleavage of the 30-residue signal sequence after puromycin termination. Nascent chain transport, per se, is apparently dependent upon neither ribonucleotide hydrolysis nor continued elongation of the polypeptide once a functional ribosome membrane junction has been established. PMID- 3097030 TI - Identification of the chick neural retina cell surface N acetylgalactosaminyltransferase using monoclonal antibodies. AB - Intact embryonic chick neural retina cells have at their surface an N acetylgalactosaminyltransferase which catalyzes the incorporation of N acetylgalactosamine from UDP-N-acetylgalactosamine into endogenous macromolecular acceptors. The enzyme along with its endogenous acceptors can be isolated as a particulate complex following treatment of membrane-enriched fractions with Triton X-100. In this paper we report on two separate fusions generating monoclonal antibodies: one using as immunogen the particulate complex and the second using as immunogen a soluble N-acetylgalactosaminyltransferase found in tissue-culture-conditioned medium which lacks endogenous acceptor activity. Antibodies from both fusions recognize an antigen which is tightly associated with the particulate transferase/acceptor complex and a soluble antigen having N acetylgalactosaminyltransferase activity toward exogenously added acceptors. The antibodies recognize a component of ca Mr 220,000, which shows N acetylgalactosaminyltransferase activity after SDS-gel electrophoresis and transfer to nitrocellulose. This component comigrates on two-dimensional gel electrophoresis with an iodinatable cell surface component whose presence at the cell surface correlates with endogenous transferase activity. We conclude that the antibodies recognize the transferase enzyme itself. Immunohistochemical analysis shows that the enzyme is initially localized throughout the embryonic neural retina in a pattern indicative of a cell surface disposition but becomes restricted to the outer plexiform layer and to outer segments in the adult. PMID- 3097029 TI - Protein p38: an integral membrane protein specific for small vesicles of neurons and neuroendocrine cells. AB - An intrinsic membrane protein of brain synaptic vesicles with Mr 38,000 (p38, synaptophysin) has recently been partially characterized (Jahn, R., W. Schiebler, C. Ouimet, and P. Greengard, 1985, Proc. Natl. Acad. Sci. USA, 83:4137-4141; Wiedenmann, B., and W. W. Franke, 1985, Cell, 41:1017-1028). We have now studied the presence of p38 in a variety of tissues by light and electron microscopy immunocytochemistry and by immunochemistry. Our results indicate that, within the nervous system, p38, like the neuron-specific phosphoprotein synapsin I, is present in virtually all nerve terminals and is selectively associated with small synaptic vesicles (SSVs). No p38 was detectable on large dense-core vesicles (LDCVs). p38 and synapsin I were found to be present in similar concentrations throughout the brain. Outside the nervous system, p38 was found in a variety of neuroendocrine cells, but not in any other cell type. In neuroendocrine cells p38 was localized on a pleiomorphic population of small, smooth-surfaced vesicles, which were interspersed among secretory granules and concentrated in the Golgi area, but not on the secretory granules themselves. Immunoblot analysis of endocrine tissues and cell lines revealed a band with a mobility slightly different from that of neuronal p38. This difference was attributable to a difference in glycosylation. The finding that p38, like synapsin I, is a component of SSVs of virtually all neurons, but not of LDCVs, supports the idea that SSVs and LDCVs are organelles of two distinct pathways for regulated neuronal secretion. In addition, our results indicate the presence in a variety of neuroendocrine cells of an endomembrane system, which is related to SSVs of neurons but is distinct from secretory granules. PMID- 3097031 TI - Structure and function of human tissue-type plasminogen activator (t-PA). AB - Full-length tissue-type plasminogen activator (t-PA) cDNA served to construct deletion mutants within the N-terminal "heavy" (H)-chain of the t-PA molecule. The H-chain cDNA consists of an array of structural domains homologous to domains present on other plasma proteins ("finger," "epidermal growth factor," "kringles"). These structural domains have been located on an exon or a set of exons. The endpoints of the deletions nearly coincide with exon-intron junctions of the chromosomal t-PA gene. Recombinant t-PA deletion mutant proteins were obtained after transient expression in mouse Ltk- cells, transfected with SV40 pBR322-derived t-PA cDNA plasmids. It is demonstrated that the serine protease moiety of t-PA and its substrate specificity for plasminogen is entirely contained within the C-terminal "light" (L)-chain of the protein. The presence of cDNA, encoding the t-PA signal peptide preceding the remaining portion of t-PA, suffices to achieve secretion of (mutant) t-PA into the medium. The stimulatory effect of fibrin on the plasminogen activator activity of t-PA was shown to be mediated by the kringle K2 domain and, to a lesser extent, by the finger domain. The other domains on the H-chain, kringle K1, and the epidermal growth-factor like domain, do not contribute to this property of t-PA. These findings correlate well with the fibrin-binding properties of the rt-PA deletion-mutant proteins, indicating that stimulation of the activity is based on aligning of the substrate plasminogen and its enzyme t-PA on the fibrin matrix. The primary target for endothelial plasminogen activator inhibitor (PAI) is located within the L-chain of t-PA. Deleting specific segments of t-PA H-chain cDNA and subsequent transient expression in mouse Ltk- cells of t-PA deletion-mutant proteins did not affect the formation of a stable complex between mutant t-PA and PAI. PMID- 3097032 TI - Clinical prediction rules in practice. PMID- 3097033 TI - Paul Broca: adventurer in the recesses of the mind. PMID- 3097034 TI - A young woman with swollen arm, dyspnea. PMID- 3097035 TI - The patient with chronic undiagnosed abdominal pain. PMID- 3097036 TI - Persistent fever and arthralgia in adults. PMID- 3097038 TI - Dementia in the elderly identifying reversibility. PMID- 3097037 TI - Hyponatremia: pathogenesis and management. PMID- 3097039 TI - Ventricular arrhythmias: to treat or not to treat? PMID- 3097040 TI - Managing the pain of herpes zoster. PMID- 3097041 TI - Liver abnormalities and persistent pain in limbs. PMID- 3097042 TI - Selective preconcentration of polynuclear aromatic hydrocarbons and polychlorinated biphenyls by in situ metal hydroxide precipitation. AB - An investigation of selective concentration of analytes from aqueous samples by in situ magnesium hydroxide precipitation, as described by Faltusz, has yielded the following results: the method is selective for polycyclic aromatic hydrocarbons and polychlorinated biphenyls of higher molecular weight: it discriminates strongly against acidic molecules, and other neutral and basic molecules are only partially recovered; a variety of metal hydroxides could evidently be used in this method, but magnesium appears to have practical advantages over some of the others; the reproducibility of analyses on pure water samples is acceptable (ca.20% relative standard deviation), but the results from natural samples show lower recovery and wider variability; a preliminary test, in which this method was used to discriminate against major amounts of interfering solutes, shows promise that this technique might have unique advantages in certain situations. PMID- 3097043 TI - Clean-up and separation of chlorobiphenyl isomers after synthesis by Cadogan coupling using preparative high-performance liquid chromatography. PMID- 3097044 TI - Thin-layer chromatography of isosorbide dinitrate, nitroglycerin and their degradation products. PMID- 3097045 TI - Estimation of mesna and dimesna in plasma and urine by high-performance liquid chromatography with electrochemical detection. PMID- 3097046 TI - Fluorimetric determination of fluvoxamine or clovoxamine in human plasma after thin-layer chromatographic or high-performance liquid chromatographic separation. PMID- 3097048 TI - Strategies for monitoring the cost and quality of care. PMID- 3097047 TI - Determination of platelet-megakaryocyte regeneration time in painters occupationally exposed to organic solvents. AB - An improved method for the determination of the regeneration time of human platelets is presented. The platelet-megakaryocyte regeneration times of painters exposed to organic solvents (n = 5; age range 23-48 years) were compared with a reference group (n = 5; age range 23-46 years) not occupationally exposed to solvents. After purification and extraction of the samples, they were analysed by high-performance liquid chromatography. The results showed that the painters have a shorter regeneration time (range 4.4-5.2 days) than the reference group (range 5.2-6.9 days) and indicate that solvent exposure may be associated with an increase in platelet turnover in man. PMID- 3097049 TI - Fetal heart monitor strip documentation: examining cost and benefit. PMID- 3097050 TI - Cost containment ideas in the long-term care setting. PMID- 3097051 TI - An integrative approach to quality assurance. PMID- 3097053 TI - Blockade of the spontaneous midcycle gonadotropin surge in monkeys by RU 486: a progesterone antagonist or agonist? AB - Preovulatory ovarian secretion of progesterone (P4), several hours before the onset of the typical midcycle gonadotropin surge, occurs in humans and monkeys. We investigated the potentially obligatory role of preovulatory P4 secretion in stimulating the midcycle LH surge by administering a potent P4 antagonist, RU 486(17 beta-hydroxy-11 beta-[4-dimethylaminophenyl-1]17 alpha-[prop-1-ynyl]estra 4,9-dien-3-one), to sexually mature, normally ovulatory cynomolgus monkeys on days 10-12 of the menstrual cycle (n = 18). Monkeys were randomized to receive RU 486 alone (5 mg/day, im; group I); RU 486 plus dexamethasone (1 mg/day, im; group II); dexamethasone alone (group III); or vehicle (ethanol; 0.5 ml; group IV). Before drug treatment, the follicular phases were quite similar among groups. The administration of RU 486 blocked (delayed) the expected gonadotropin surge, despite rising estrogen concentrations (greater than 250 pg/ml). The expected LH surge was delayed by RU 486 (n = 5) or RU 486 with dexamethasone (n = 3) until 36 +/- 7 (+/- SEM) and 27 +/- 8 days in groups I and II, respectively. In contrast, groups III (n = 3) and IV (n = 5) had timely midcycle surges after the administration of dexamethasone or vehicle alone (4 +/- 2 and 6 +/- 2 days, respectively). The intermenstrual interval was lengthened by RU 486 administration in both group I and II animals (61 +/- 6 and 54 +/- 6 days) compared to controls (30 +/- 2; P less than 0.0001). In summary, RU 486 effectively blocked imminent midcycle gonadotropin surges, delayed subsequent folliculogenesis, and significantly extended the menstrual cycle length. If RU 486 acted as a pure P4 antagonist, then P4 is necessary for timely midcycle gonadotropin surges to occur. However, recent evidence showing agonistic properties of RU 486 (in the virtual absence of P4) at both endometrial and pituitary levels may favor a P4-like (agonistic) blockade of the estrogen-induced FSH/LH surges by RU 486. PMID- 3097052 TI - Sex steroid, gonadotropin, cortisol, and prolactin levels in healthy, massively obese women: correlation with abdominal fat cell size and effect of weight reduction. AB - To examine hormonal status in obese, gynecologically normal women we studied 25 regularly menstruating, massively obese (mean weight, 120 kg) women participating in a weight reduction program and 25 age-matched normal weight (mean weight, 60 kg) women. Serum 17 beta-estradiol (E2), estrone (E1), androstenedione (A), dehydroepiandrosterone sulfate, testosterone, LH, FSH, PRL, and cortisol concentrations were measured during the follicular phase of the menstrual cycle. Waist to hip ratio and abdominal fat cell size were measured at the beginning of the study. The serum levels of E2 (P less than 0.04) as well as those of A, SHBG, and LH (P less than 0.002) were lower in the obese group. Consequently, the testosterone to SHBG ratio and the E1 to A ratio were higher and the LH to FSH ratio was lower in this group. Waist to hip ratio did not correlate with the levels of circulating hormones or SHBG, but an inverse correlation was found between abdominal fat cell size and A as well as the LH to FSH ratio in the nonhirsute women of the obese group. Subsequent to moderate weight reduction (13.2 kg), serum A and E1 levels (P less than 0.01) increased, and serum cortisol levels decreased (P less than 0.001). Thus, massive obesity is associated with abnormalities in hormonal balance in gynecologically symptomless women, there being an association between E1, E2, A, LH, cortisol, and relative weight and/or abdominal fat cell size. PMID- 3097054 TI - Treatment of endometriosis in monkeys: effectiveness of continuous infusion of a gonadotropin-releasing hormone agonist compared to treatment with a progestational steroid. AB - The use of a GnRH agonist or a progestational steroid (levonorgestrel) for the treatment of endometriosis in monkeys was compared. Four monkeys with spontaneous endometriosis were treated for 6 months with a continuous infusion of a GnRH agonist (25 micrograms/day). Five animals with surgically induced endometriosis were treated with the same agonist for 3 months. An additional group of five monkeys with surgically induced endometriosis was treated orally with levonorgestrel (1 mg/kg X day), while a final group of four monkeys served as untreated controls. During agonist treatment, the four monkeys with spontaneous endometriosis gained body weight and had a greater than 80% decline in cyst size (representing a decline in secretory activity). Monkeys with surgically induced endometriosis had almost total resolution of endometrial lesions during agonist treatment, which was maintained throughout a 4-month posttreatment period. After initial stimulation at the onset of the GnRH agonist infusion, serum LH, FSH, estradiol, and progesterone levels decreased to near the levels of detection, where they remained until treatment was terminated. In comparison, levonorgestrel reduced endometrial lesion size, but the monkeys did not resume normal cycles as early as those treated with the agonist. Levonorgestrel-treated monkeys had normal serum LH and FSH levels, but low serum estradiol and progesterone levels. The results of this study indicate that either continuous infusion of a GnRH agonist or administration of levonorgestrel is effective for treating endometriosis in monkeys. The hormonal data suggest that the GnRH agonist acts at the level of the hypothalamus and pituitary, whereas levonorgestrel acts at the ovarian level. PMID- 3097055 TI - Ovulation induction with human menopausal gonadotropin compared to human urinary follicle-stimulating hormone results in a significant shift in follicular fluid androgen levels without discernible differences in granulosa-luteal cell function. AB - Follicular fluid estradiol, progesterone, testosterone, and androstenedione levels were compared in 2 groups of spontaneously ovulatory women undergoing ovulation induction with human menopausal gonadotropin (hMG; which contains equal amounts of LH and FSH) or human urinary FSH (huFSH). The results were correlated with the ratios of embryo cleavage and pregnancy. Although significantly more FSH [1268 +/- 38 (+/- SEM) vs. 953 +/- 38 IU; P less than 0.05] was required for equivalent hyperstimulation in hMG compared to huFSH cycles, the number of oocytes retrieved and fertilized and the number of embryos transferred were similar for the 2 ovulation induction protocols. Forty-two follicles from 21 women stimulated with hMG and 38 follicles from 15 women stimulated with huFSH were examined and found to be representative of the total cohort of aspirated follicles. Follicular fluid estradiol and progesterone levels were similar, but hMG-stimulated follicles contained significantly more testosterone [7.83 +/- 0.52 (+/- SEM) vs. 6.30 +/- 0.42 ng/ml; P less than 0.03] and less androstenedione (24.4 +/- 3.6 vs. 37.8 +/- 5.0 ng/ml; P less than 0.03) than did huFSH-stimulated follicles. Embryonic cleavage rates were similar for all fertilized oocytes from both hMG- and huFSH-stimulated cycles, although pregnancy rates were significantly higher in huFSH cycles (40% vs. 9.5%; P less than 0.05). In addition, aromatase activity, progesterone production, and [125I]hCG-binding activity were compared in granulosa-luteal cells isolated from some of these women. Cells from 21 follicles from 9 women stimulated with hMG and 24 follicles from 9 women stimulated with huFSH were studied. There were no significant differences in aromatase activity, progesterone production, or [125I]hCG binding. Thus, the presence or absence of exogenous LH during ovulation induction with FSH has little direct effect on granulosaluteal cell function. However, the presence of LH during ovulation induction with FSH does appear to alter thecal androgen metabolism, resulting in higher testosterone and lower androstenedione levels in follicular fluid. Such a shift in androgen milieu may impair oocyte development and successful implantation. PMID- 3097056 TI - Acromegaly and pheochromocytoma: a multiple endocrine syndrome caused by a plurihormonal adrenal medullary tumor. AB - A 42-yr-old man with congestive heart failure and diabetes mellitus was found to have acromegaly and a pheochromocytoma. Serum GH-releasing hormone (GHRH) levels were elevated (2.34 ng/dl; normal, less than 0.02 ng/dl), suggesting that the acromegaly was caused by ectopic secretion of GHRH. Postmortem examination revealed that the right adrenal gland contained a pheochromocytoma in which GHRH was demonstrated by immunohistochemical studies. Gel permeation chromatography combined with the use of two GHRH antisera showed that GHRH-(1-44)-NH2 was a predominant form of the hormone. When the RNA from the tumor was extracted and analyzed by Northern gel blotting, two mRNA species were identified, with transcripts corresponding to 1600 and 780 base pairs. The pituitary gland was enlarged, but no distinct adenoma was found. Diffuse and nodular hyperplasia of somatotrophs in some areas resembling adenoma was identified on histological examination. These findings indicate that GH excess accompanied by somatotroph hyperplasia and acromegaly were secondary to a pheochromocytoma which secreted not only catecholamines but also GHRH. PMID- 3097057 TI - Reduced affinity for thyroxine in two of three structural thyroxine-binding prealbumin variants associated with familial amyloidotic polyneuropathy. AB - T4-binding prealbumin (TBPA), a protein synthesized by the liver, circulates as a tetramer and transports 15-20% of T4. We studied 3 variants of the TBPA monomer recently identified in serum and amyloid fibrils of patients affected by familial amyloidotic polyneuropathy (FAP). They represent single amino acid substitutions at positions 30 (type I), 60 (Appalachian), and 84 (type II). Tests of thyroid function and the apparent association constant (Ka) of T4 binding to TBPA were measured in whole serum from 14 carriers of FAP identified clinically, by amino acid sequence analysis, or by DNA restriction fragment analysis. Significant reduction of Ka was found in subjects with FAP types I and II, but not in subjects with the Appalachian type. Mean (+/- SD) values of 0.24 +/- 0.08 X 10(7) M-1 for type I and 0.26 +/- 0.10 X 10(7) M-1 for type II were significantly (P less than 0.0001) lower than those for normal relatives (1.39 +/- 0.30 X 10(7) M 1) or unrelated normal subjects (1.41 +/- 0.18 X 10(7) M-1). The mean Ka value for the five subjects with FAP of the Appalachian type was slightly but not significantly reduced (1.08 +/- 0.11 X 10(7) M-1). There was no overlap of individual Ka values of subjects with types I and II TBPA with those of subjects from all other groups. Abnormalities of thyroid function included slight but significant reductions of the mean total serum T4 concentration in the subjects with type II FAP and the mean serum total T3 concentration in those with type I FAP. Four subjects with FAP (two type II and two of the Appalachian type) had biochemical evidence of hypothyroidism. The three subjects with total serum T3 levels below the limit of normal had amyloid cardiomyopathy. These results indicate that TBPAs from subjects with FAP types I and II have relatively lower affinity for T4. Although none of the substituted amino acids in these variant TBPAs contribute directly to the surface of the putative T4-binding site, the side chains of amino acids 30 and 84, but not 60, interact with internal residues of the beta-structure which forms the presumed binding site, in agreement with our results of Ka measurements. The high incidence of hypothyroidism is due to the probably fortuitous occurrence of Hashimoto's thyroiditis as well as to partial destruction of the thyroid gland by amyloid deposits. PMID- 3097058 TI - Influence of testosterone therapy on clinical and immunological features of autoimmune diseases associated with Klinefelter's syndrome. AB - To examine the role of sex steroid hormones in the development of autoimmune diseases, we studied five patients with Klinefelter's syndrome associated with autoimmune disease, three of whom had Sjogren's syndrome (SS) and two of whom had systemic lupus erythematosus (SLE). Serum testosterone (T) and LH levels, antinuclear antibodies (ANA) and rheumatoid factor (RF) titers, erythrocyte sedimentation rate (ESR), hemolytic complement (CH50) levels, and peripheral T lymphocyte subsets (OKT3+, OKT4+, and OKT8+) were measured before treatment, after 60 days of placebo treatment, and after 60 days of oral T undecanoate (TU) treatment. Before treatment and after placebo, with respect to normal men, the patients had lower serum T and higher LH levels, lower percentages and absolute values of OKT3+ (total T lymphocytes) and OKT8+ (suppressor/cytotoxic T lymphocytes) cells, and, consequently, an increased OKT4/OKT8 ratio. Hemolytic complement (CH50) in serum was below normal in the two patients with SLE, while it was normal in the patients with SS. The ESR was above normal in all patients, and all had high titers of ANA and RF. After TU therapy, serum T levels increased and LH levels decreased, but not to normal. OKT3+ and OKT8+ cells and the OKT4/OKT8 ratio became normal, and RF and ANA titers decreased. The CH50 level did not change in the SS patients, while it increased to normal in the two patients with SLE. The ESR decreased in all patients during therapy. Furthermore, after TU therapy, both the SS and SLE patients had a clinical remission of their autoimmune disease. Our results indicate a therapeutic effect of T on autoimmune diseases in patients with hypogonadism and Klinefelter's syndrome. PMID- 3097059 TI - Effect of oral glucose administration on plasma growth hormone-releasing hormone (GHRH)-like immunoreactivity levels in normal subjects and patients with idiopathic GH deficiency: evidence that GHRH is released not only from the hypothalamus but also from extrahypothalamic tissue. AB - Using a specific and sensitive RIA for GH-releasing hormone (GHRH), we examined the effect of oral administration of 75 g glucose on peripheral plasma GHRH-like immunoreactivity (GHRH-LI) in normal subjects (n = 12) and patients with idiopathic GH deficiency (IGHD) (n = 6). The normal subjects had two peaks of plasma GHRH-LI after oral glucose administration. The initial peak GHRH-LI levels occurred 30-150 min after glucose ingestion and corresponded to an increase in blood glucose. The increment in plasma GHRH-LI levels 30 min after glucose ingestion [7.4 +/- 2.4 (+/- SEM) pg/ml] was significantly higher (P less than 0.05) than that during a control study. Second peaks in plasma GHRH-LI occurred 3.5-6 h after glucose ingestion, and the mean increment 5 h after glucose ingestion was 9.4 +/- 2.4 pg/ml. This second rise of plasma GHRH-LI coincided with a significant increase in plasma GH after reactive hypoglycemia. This second GHRH-LI peak and the rise of plasma GH after hypoglycemia were absent in patients with IGHD, whereas the first peak of plasma GHRH-LI appeared shortly after glucose ingestion in these patients as well as in normal subjects. In addition, hypoglycemia produced by iv injection of regular insulin (0.1 U/kg) was not accompanied by increases in plasma GHRH-LI and GH levels in patients with IGHD, whereas insulin-induced hypoglycemia resulted in significant elevations of both plasma GHRH-LI and GH levels in normal subjects. These findings suggest that peripheral plasma GHRH-LI is derived from the hypothalamus as well as from an extrahypothalamic source(s); extrahypothalamic GHRH is released shortly after glucose ingestion; and secretion of GHRH from the hypothalamus is stimulated by hypoglycemia. PMID- 3097060 TI - Impaired monocyte-to-macrophage maturation in patients with lymphadenopathy syndrome. AB - The in vitro maturation of monocytes from patients with lymphadenopathy syndrome (LAS) was studied by means of enzymatic activity performed during a 7-day incubation period. Monocytes from LAS patients, healthy homosexuals, and healthy heterosexuals were assayed for beta-galactosidase and beta-N acetylglucosaminidase activity on days 3, 5, and 7 of culture. The LAS monocytes had significantly lower (P less than 0.01) absolute levels of both enzymes compared with controls or healthy homosexual subjects. All three groups showed a linear increase in enzyme activity over time. There was no statistical difference between the slopes of the curves of enzyme activity vs time for the three groups, indicating that the rate of increase in enzyme activity was similar for the groups. These results suggest that monocyte-to-macrophage maturation is impaired in LAS. LAS monocytes are initially less mature than those of healthy homosexuals or heterosexuals but retain their capacity to mature during incubation in vitro. PMID- 3097061 TI - Abnormality of Leu 2+7+ cells in acquired immune deficiency syndrome (AIDS), AIDS related complex, and asymptomatic homosexuals. AB - Peripheral blood mononuclear cells from patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC), asymptomatic homosexuals, and healthy heterosexuals were analyzed for the proportions and numbers of Leu 7+ cells and double-labeled Leu 2+7+ cells and for the natural killer functions. A significant increase in the proportions and numbers of Leu 7+ cells was observed in patients with AIDS and ARC and in asymptomatic homosexuals compared to healthy heterosexual men. The proportions of Leu 2+7+ cells were significantly increased in AIDS, ARC, and asymptomatic homosexuals, whereas the numbers were increased in asymptomatic homosexuals and ARC but not in AIDS compared to heterosexual controls. A significant increase in the number of Leu 2+7+ cells was observed in AIDS with Kaposi's sarcoma but not in AIDS with opportunistic infections. The natural killer function was significantly depressed in patients with AIDS and ARC and in asymptomatic homosexuals. These data suggest that the quantitative abnormalities of Leu 2+7+ cells appear early during the evolution of immunologic changes in HTLV III/LAV infection. PMID- 3097062 TI - Improved, computer-generated system for pyocin typing of Pseudomonas aeruginosa. AB - We applied numerical clustering algorithms to the selection of a new indicator strain set for the pyocin typing of Pseudomonas aeruginosa. The new indicator set is composed of selected indicator strains from the sets described in 1966 by Gillies and Govan (J. Pathol. Bacteriol. 91:339-345) and in 1974 by Jones, Zakanycz, Thomas, and Farmer (Appl. Microbiol. 27:400-406) and is designated the G-F set. This indicator set consists of 14 indicator strains which typed 99.5% of 114 test cultures, has a high degree of discrimination (10 patterns encompass 50% of the test strains), and provides 62.3% reproducibility of the same typing pattern in duplicate tests done on different days. The G-F set of indicator strains provides slightly higher percentages of typable cultures than either of the other two sets, has greater discriminatory capability, and is more reproducible than they are. We recommend that the G-F set of indicator strains be used instead of the two other sets for pyocin typing of P. aeruginosa. We also tested a recently described overlay procedure for pyocin testing of P. aeruginosa and found it to be superior to previous methods in that it is easier to perform, it provides answers in only 24 h instead of 48 h, and it can be used to type mucoid strains (which previous techniques could not readily do). Thus, the application of numerical clustering algorithms and use of a revised typing procedure have produced an improved system for pyocin typing of P. aeruginosa. Similar procedures may be applicable to other typing systems. PMID- 3097063 TI - Identification of a new group of Chlamydia psittaci strains called TWAR. AB - A new group of Chlamydia psittaci strains has been identified. They are called TWAR after the laboratory designation of the first two isolates. Twelve strains were isolated from pharyngeal swabs of different persons with acute respiratory disease in Seattle, Wash., during 1983 to 1986. One strain was obtained from the eye of a child during the trachoma vaccine study in Taiwan in 1965. Nine strains were characterized in this study. TWAR organisms formed intracytoplasmic inclusions in HeLa cells which were morphologically typical of C. psittaci and iodine stain negative (contained no glycogen). Immunological analysis with various chlamydia-specific monoclonal antibodies revealed that TWAR strains belong to the genus Chlamydia, are distinct from C. trachomatis, and are serologically unique among C. psittaci. All TWAR strains so far isolated appear identical serologically. TWAR organisms grew poorly in egg and cell cultures and demonstrated low virulence to mice by intracerebral, intranasal, and intravenous inoculation. Available data suggest that the TWAR strain is a primary human pathogen. PMID- 3097064 TI - Antimicrobial activity of cefmetazole (CS-1170) and recommendations for susceptibility testing by disk diffusion, dilution, and anaerobic methods. AB - Cefmetazole, formerly CS-1170, was found to have antimicrobial activity slightly superior to that of cefoxitin but a clinically usable antimicrobial spectrum that should be considered identical to that of cefoxitin. Disk diffusion and dilution test methods with cefmetazole correlated highly (r, greater than or equal to 0.95) with cefoxitin results. The recommended 30-micrograms cefmetazole disk interpretive breakpoints for susceptibility and resistance were greater than or equal to 18 mm (MIC, less than or equal to 8.0 micrograms/ml) and less than or equal to 14 mm (MIC, greater than or equal to 32 micrograms/ml), respectively. Cefmetazole and cefoxitin should be considered to be in the same antimicrobial spectrum class, requiring separate testing for other cephalosporins such as cephalothin, cefamandole, cefuroxime, and cefotetan. Recommended interpretive criteria performed well for fastidious organisms (Haemophilus influenzae, Neisseria meningitidis, and Branhamella catarrhalis) and for broth microdilution tests with anaerobes. Cefmetazole and cefoxitin broth disk elution tests for anaerobic bacteria produced higher rates of false susceptibility results. PMID- 3097065 TI - Comparative tests for detection of plague antigen and antibody in experimentally infected wild rodents. AB - The enzyme-linked immunosorbent assay (ELISA) was compared with other standard tests for detection of plague (Yersinia pestis) antibody and antigen in multimammate mice (Mastomys coucha and M. natalensis) which were experimentally infected and then killed at daily intervals postinoculation. For detection of antibody in sera from M. natalensis, the immunoglobulin G (IgG) ELISA was equivalent in sensitivity to passive hemagglutination and more sensitive than the IgM ELISA and complement fixation. Antibody was first detected on postinfection day 6 by all four tests, but IgM ELISA titers had declined to undetectable levels after 8 weeks. For detection of fraction 1 Y. pestis antigen in rodent organs, the ELISA was less sensitive than fluorescent antibody but more sensitive than complement fixation or immunodiffusion. Plague fraction 1 antigen was detected in 16 of 34 bacteremic sera from M. coucha and M. natalensis. The threshold sensitivity of the ELISA was approximately 10(5) Y. pestis per ml. PMID- 3097066 TI - Effect of holding temperature on isolation of Neisseria gonorrhoeae. AB - The effect of holding temperature on the recovery of Neisseria gonorrhoeae was studied. From 300 specimens tested, Thayer-Martin medium plates inoculated and incubated in the presence of CO2 at 35, 22, and 4 degrees C for 24 h before incubation at 35 degrees C yielded 100, 96, and 95% of all isolates ultimately recovered from 82 positive specimens. Although there was a decrease in the quantity of organisms recovered, initial incubation of specimens under refrigeration or at room temperature yielded greater than or equal to 95% of the positive specimens. PMID- 3097067 TI - Comparative evaluation of New York City and modified Thayer-Martin media for isolation of Neisseria gonorrhoeae. AB - Commercially manufactured New York City (NYC) medium and modified Thayer-Martin (MTM) medium were compared for their ability to isolate Neisseria gonorrhoeae from clinical specimens. Twenty-seven public health laboratories throughout California evaluated 4,802 specimens collected from patients attending either sexually transmitted disease or family planning clinics. Total of 726 and 737 N. gonorrhoeae isolates were recovered from NYC and MTM medium, respectively. Although less contamination was noted on NYC medium, MTM medium was equivalent to commercially prepared NYC medium for the isolation of N. gonorrhoeae from clinical specimens. PMID- 3097069 TI - Susceptibility testing of slowly growing mycobacteria by a microdilution MIC method with 7H9 broth. AB - Based on previous success with rapidly growing mycobacteria, a microdilution MIC system was devised for slowly growing mycobacterial species using 7H9 broth. Test drugs included isoniazid, rifampin, ethambutol, streptomycin, clofazamine, and sulfamethoxazole. Sixty isolates of four mycobacterial species, including Mycobacterium tuberculosis, from patients who had never received drug therapy were evaluated in the system, as well as 25 drug-resistant isolates and 11 control strains. MICs were read when good macroscopic control growth was evident, a period which varied with each species. Most species exhibited a narrow range of MICs with easily discernible growth endpoints. The aminoglycosides, ethambutol, clofazamine, and sulfamethoxazole were the only drugs with activity against all species at clinically achievable levels in serum. Correlation between susceptibilities by the proportion method in agar with single drug concentrations and the broth method were excellent for M. tuberculosis, M. kansasii, and M. marinum for isoniazid, rifampin, and ethambutol. Isolates of the M. avium complex were much more susceptible in broth than in agar for rifampin, ethambutol, and streptomycin. Given the successful transition of most microbiology laboratories to MIC plates for other bacterial species, this method would allow for testing of multiple drugs at multiple concentrations and has good potential for evaluation of drug combinations and drug-resistant isolates. PMID- 3097068 TI - Antibody response in group B meningococcal disease determined by enzyme-linked immunosorbent assay with serotype 15 outer membrane antigen. AB - To elucidate pathogenic aspects and serodiagnostic possibilities for meningococcal disease, we investigated levels of specific antimeningococcal immunoglobulin G (IgG), IgA, and IgM in serum by using an enzyme-linked immunosorbent assay with outer membrane antigen prepared from a Neisseria meningitidis B:15:P1.16 strain. Serum samples were drawn on hospital admission as well as during convalescence from patients suspected of purulent meningitis or meningococcal septicemia, and single samples were drawn from population controls. A total of 637 samples were examined blindly. On admission, the average antimeningococcal immunoglobulin levels were about the same in the meningococcal disease patients as in the population controls. Septicemic patients, however, had significantly lower values. During one week the mean specific immunoglobulin levels in meningococcal-disease patients increased 6 times for IgG, 14 times for IgA, and 5 times for IgM. Children younger than 1 year showed a modest and more slowly developing antibody response. There were no statistically significant differences in average antibody responses among patients infected with meningococci of different serotypes. At 100% specificity, the increase in IgG, IgA, and IgM yielded diagnostic sensitivities for meningococcal disease of 84, 52, and 66%, respectively. One of seven serum pairs from the patient control group with unknown etiology was positive for meningococcal disease in this assay. The patients with meningococcal disease originally diagnosed only by clinical signs and symptoms showed a slightly lower rate of seroconversion than the patients in whom the diagnosis was supported by test results showing a systemic Neisseria meningitidis isolate. PMID- 3097070 TI - Aeration selects for mucoid phenotype of Pseudomonas aeruginosa. AB - A mucoid strain of Pseudomonas aeruginosa isolated from a patient with cystic fibrosis and its nonmucoid revertant were grown in a chemically defined alginate promoting medium under batch and continuous culture conditions. Selection for the mucoid and nonmucoid phenotype was accomplished by varying the levels of air available to the culture. The addition of air at a rate of 0.5 liters/min to the nonmucoid revertant growing under batch or continuous culture conditions resulted in a greater than 50% decrease in viability over a 10-h incubation period. In contrast, aeration of the mucoid culture maintained a totally mucoid population and there was no decrease in viability over a 55-h incubation. Aeration of a mixed population of the mucoid and nonmucoid phenotype (1:1) resulted in selection for the mucoid phenotype within the first 20 h of cocultivation. The correlation between the mucoid phenotype and alginic acid was demonstrated by the production of 580 micrograms of uronic acid per mg (dry weight) of cells by the mucoid phenotype and less than 1 microgram of uronic acid per mg (dry weight) of cells by the nonmucoid revertant. These results suggest that nonmucoid revertants may have an unusual sensitivity to aeration, which may indicate a mechanism for natural selection of the mucoid phenotype in vivo. PMID- 3097071 TI - The mechanism of inhibition of experimental allergic encephalomyelitis in the rat by monoclonal antibody against CD4. AB - Lewis rats with actively induced or passively transferred experimental allergic encephalomyelitis (EAE) were treated with a monoclonal antibody (MAb) which binds to the CD4 antigen of rat helper/inducer T cells. Actively immunized animals treated at the first onset of clinical signs experienced only a mild form of the disease and rapidly recovered while the majority of those treated prophylactically never showed clinical signs of EAE. Passively transferred EAE was also completely inhibited with anti-CD4 MAb. In treated animals which exhibited only mild clinical signs of EAE, spinal cord and cerebellar leukocyte infiltrates were quite similar to those in untreated rats but where anti-CD4 MAb treatment completely prevented clinical EAE, histological signs were minimal or absent. Like Lewis rats which have recovered naturally from EAE, those treated with anti-CD4 MAb were both resistant to a secondary challenge with myelin basic protein and harboured potential encephalitogenic cells which were capable of transferring disease to recipient rats. Disease in these recipients was, however, of much greater severity than that experienced by animals receiving cells from naturally recovered (untreated) donors. These data demonstrate that administration of anti-CD4 MAb to rats can prevent EAE by a mechanism which does not ablate the encephalitogenic CD4+ cells or prevent the development of resistance to EAE but which may inhibit the disease by preventing the function of already activated effector cells. PMID- 3097072 TI - Treatment of clinical experimental allergic encephalomyelitis in the rat with monoclonal antibodies. AB - An anti-CD4 monoclonal antibody of the IgG2a subclass, OX35, and an anti-I-A monoclonal antibody (IgG1) were used in vivo to treat experimental allergic encephalomyelitis in the Lewis rat. The anti-CD4 antibody was as effective in shortening the duration of the disease as the previously reported use of W3/25 (Brostoff and Mason, J. Neuroimmunol., 10 (1984) 331-340). It did not appear necessary for the antibody treatment to remove the CD4+ cells from the circulation in order to show an effect on the clinical course of the disease. The anti-I-A antibody did not have any noticeable effect in this disease model. PMID- 3097073 TI - Kappa-chain gene rearrangement in an apparent T-lineage lymphoma. AB - We describe a 10-yr-old boy with T-lineage non-Hodgkin's lymphoma. He had a mediastinal mass, swollen supraclavicular lymph nodes, and pleural effusion. A supraclavicular lymph node biopsy under light microscopy showed a malignant lymphoma of diffuse lymphoblastic type. Most of the cells taken from the malignant pleural effusion expressed T cell-associated antigens such as Leu-1 and OKT 8. To confirm these antigens as T-lineage lymphoma, we examined genomic DNA from malignant cells obtained from the pleural effusion. As was expected, T cell receptor beta-chain gene rearrangements were demonstrated. However, when the immunoglobulin gene organization was analyzed, we detected rearrangements in both the heavy- and kappa-chain genes. To our knowledge, this is the first case in which kappa-chain gene rearrangement was detected in apparent T-lineage cells. These findings provide important information relating to determination of the cellular lineage of lymphoid malignancy. PMID- 3097074 TI - Renal bicarbonate reabsorption in the rat. I. Effects of hypokalemia and carbonic anhydrase. AB - Free-flow micropuncture studies were carried out on superficial rat proximal and distal tubules to assess the participation of different nephron segments in bicarbonate transport. Particular emphasis was placed on the role of the distal tubule, and micro-calorimetric methods used to quantitate bicarbonate reabsorption. Experiments were carried out in control conditions, during dietary potassium withdrawal, and after acute intravenous infusions of carbonic anhydrase. We observed highly significant net bicarbonate reabsorption in normal acid-base conditions as evidenced by the maintenance of significant bicarbonate concentration gradients in the presence of vigorous fluid absorption. Distal bicarbonate reabsorption persisted in hypokalemic alkalosis and even steeper transepithelial concentration gradients of bicarbonate were maintained. Enhancement of net bicarbonate reabsorption followed the acute intravenous administration of carbonic anhydrase but was limited to the nephron segments between the late proximal and early distal tubule. The latter observation is consistent with a disequilibrium pH along the proximal straight tubule (S3 segment), the thick ascending limb of Henle, and/or the early distal tubule. PMID- 3097075 TI - Distal tubule bicarbonate accumulation in vivo. Effect of flow and transtubular bicarbonate gradients. AB - We have performed microperfusion studies on distal tubules of normal and alkalotic rats in an attempt to demonstrate in vivo bicarbonate secretion. All perfusion solutions were free of phosphate and other nonbicarbonate buffers. In both normal and alkalotic rats, distal perfusions elicited significant tCO2 entry only at high flow (24 nl/min). Even when perfusate tCO2 concentration closely matched plasma tCO2 concentration (30 mM tCO2), significant tCO2 entry again occurred at high flow. This was associated with a rise of the perfusate tCO2 concentration, which indicated net entry of tCO2 against a concentration gradient. In this "symmetrical" perfusion situation, acetazolamide blockade prevented tCO2 entry. Accordingly: distal tubule tCO2 entry is demonstrable in both alkalotic and normal rats at high flow rates; increasing perfusate tCO2 concentration can suppress tCO2 entry; and entry can occur in the absence of a gradient and this effect can be blocked by acetazolamide. PMID- 3097078 TI - Determination of in vivo concentration-time profiles of chlorhexidine and noxythiolin bladder irrigations. AB - The in vivo concentration-time profiles of chlorhexidine and noxythiolin bladder irrigations were determined by utilizing high-performance liquid chromatography techniques following a once daily irrigation. A total of 14 chlorhexidine irrigations established a mean concentration of 0.006% w/v, 2-3 h post irrigation. A total of 12 noxythiolin irrigations established a mean concentration of 0.266% w/v, 2-3 h post irrigation, which correlated to a mean formaldehyde concentration of 0.0119% w/v at 2-3 h, as estimated from N methylthiourea. For both solutions the minimum inhibitory concentration was exceeded for up to 5 h post irrigation, which is sufficient contact time to establish a total kill, thus indicating the possibility that a once daily irrigation may be appropriate in asymptomatic bacteriuria which utilizes either chlorhexidine or noxythiolin. PMID- 3097077 TI - Effect of protein ingestion on urinary dopamine excretion. Evidence for the functional importance of renal decarboxylation of circulating 3,4 dihydroxyphenylalanine in man. AB - Since dietary protein increases urinary dopamine (DA) excretion in animals, this study was undertaken to assess the role of DA production in the acute changes in renal function following protein ingestion in man. Excretion of DA, sodium, potassium, water, solute, and creatinine were measured in six normal men in 30 min intervals over 5 h after oral ingestion of protein and/or carbidopa, an inhibitor of DA formation from 3,4-dihydroxyphenylalanine (DOPA). Overall, protein increased urinary DA 50% (P = 0.031) while carbidopa reduced it 70% (P less than 0.0001), although suppression of DA excretion by carbidopa was not uniform over the 5 h of observation. Carbidopa doubled the level of DOPA in venous plasma and greatly magnified the DOPA response to protein. Inhibition of decarboxylase activity reduced excretion of sodium, potassium, solute and water after protein ingestion. These results indicate that extraneuronal DOPA decarboxylation in kidney contributes to acute protein-induced changes in renal function in man and suggest a general role for the decarboxylation of circulating DOPA in the expression of dopaminergic effects on the kidney in vivo. PMID- 3097076 TI - cDNA cloning of human plasminogen activator-inhibitor from endothelial cells. AB - Full-length cDNA for plasminogen activator inhibitor (PAI-1) was isolated from a human umbilical vein endothelial cell (HUVEC) lambda gt11 cDNA library. Three overlapping clones were identified by immunologic screening of 10(6) recombinant phage using a rabbit anti-human fibrosarcoma PAI-1 antiserum. The fusion proteins encoded by these three clones also react strongly with a monoclonal mouse anti human fibrosarcoma PAI-1 antibody. By nucleotide sequence analysis, PAI-1 cDNA encodes a protein containing 402 amino acids with a predicted, nonglycosylated molecular mass of 45 kD. Identity of this material as authentic PAI-1 was confirmed by the presence of high level homology with the primary amino acid sequence of an internal peptide prepared from purified rat hepatoma PAI-1. The predicted amino acid sequence also reveals extensive homology with other members of the serine protease inhibitor gene family. Cultured HUVECs contain two PAI-1 mRNA species, both encoded by a single gene, differing by 1 kb in the 3' untranslated region. The PAI-1 gene is located on human chromosome 7. PMID- 3097079 TI - Homology of cryptic plasmid of Neisseria gonorrhoeae with plasmids from Neisseria meningitidis and Neisseria lactamica. AB - DNA probe hybridisation was used to examine the relation between the cryptic plasmid from Neisseria gonorrhoeae and plasmids carried by pharyngeal isolates of Neisseria meningitidis and Neisseria lactamica. The complete gonococcal cryptic plasmid and HinfI derived digestion fragments subcloned into Escherichia coli were used to probe Southern blots of plasmid extracts. Homology was found to a plasmid of approximate molecular weight 4.5 kilobase pairs (Kb) but not to plasmids of less than 3.2 Kb or 6.5 Kb. Eleven of 16 strains of N meningitidis and two of six strains of N lactamica carried plasmids that showed strong hybridisation with the 4.2 Kb gonococcal plasmid. Hybridisation of plasmids from non-gonococcal species of neisseria with the gonococcal cryptic plasmid indicates that caution should be taken when using the cryptic plasmid as a diagnostic probe for gonorrhoea. PMID- 3097080 TI - Development of enzyme linked immunosorbent assay (ELISA) to detect antibodies to Pseudomonas aeruginosa cell surface antigens in sera of patients with cystic fibrosis. AB - An enzyme linked immunosorbent assay (ELISA) to measure free serum IgG antibodies to Pseudomonas aeruginosa in patients with cystic fibrosis was developed. Seven strains of P aeruginosa cells, treated with glutaraldehyde and representing the most commonly isolated serotypes in our cystic fibrosis unit, were used. The specificity of the test was confirmed by the absence of cross reacting antibodies to other Gram negative bacteria. The results showed differences in the titres of antibodies at different stages of P aeruginosa infection. Because of its reproducibility, specificity, and sensitivity these preliminary results suggest that this test may be of value in monitoring the progress of P aeruginosa infection in patients with cystic fibrosis. PMID- 3097081 TI - Assessment of new radioimmunoassay kit for determining urinary albumin at low concentrations: comparison with radial immunodiffusion. AB - The assay characteristics of a new radioimmunoassay kit for determining urinary albumin at low concentrations were studied. The sensitivity for urinary albumin was 2 mg/l, the analytical range 2 to 40 mg/l, and interassay coefficient of variation less than 12%. In a method comparison study entailing diabetic urine samples covering an albumin concentration of 2 to 150 mg/l the kit compared adequately with radial immunodiffusion (mean difference between methods = 2 mg/l; residual standard deviation = 4.6 mg/l), absolute variation between methods increasing with the concentration. The kit required much less skill than radial immunodiffusion but its capital and running cost were higher. PMID- 3097082 TI - Effect of substrate on indirect immunofluorescence tests for intercellular and basement membrane zone antibodies. AB - The effect of substrate on the result of indirect immunofluorescence tests for intercellular and basement membrane zone antibodies was examined by testing concurrently 288 human sera on the three substrates used most commonly for this test, that is, monkey and guinea pig esophagus and normal human skin. Seventy five sera had intercellular antibodies and 56 had basement membrane zone antibodies. The substrate influenced the results of 41% of assays for intercellular and 56% of those for basement membrane zone antibodies. Thirty-one percent of intercellular and 38% of basement membrane zone antibodies failed to react to one or more than one substrate, leading to false-negative reactions. In an additional 10% to 12% of sera, the titer of the reaction was influenced by the substrate. These results indicate that the substrate used has a major impact on the result of indirect immunofluorescence tests for antibodies to skin. The best overall single substrate was monkey esophagus, but optimal results were obtained when both monkey and guinea pig esophagus were used. PMID- 3097084 TI - Developing the nurse preceptor. PMID- 3097083 TI - Opening of blood-ocular barrier demonstrated by contrast-enhanced MR imaging. AB - Opening of the blood-ocular barrier following infusion of hyperosmolar agents into the internal carotid artery has been demonstrated by gadolinium enhanced magnetic resonance (MR) imaging. In five rhesus monkeys the disruption of the barrier was shown as increased signal intensity within the aqueous and vitreous humors. These findings suggest a potential use of contrast-enhanced MR imaging for detecting and evaluating the ocular microangiopathy of diabetic and hypertensive retinopathy and other diseases. PMID- 3097085 TI - Gerontology programming: a consortium approach in a rural area. PMID- 3097086 TI - Self-directed learning for the RN in a baccalaureate program. PMID- 3097087 TI - Motivational orientations of Kansas nurses participating in continuing education in a mandatory state for relicensure. PMID- 3097088 TI - The planning, implementation and evaluation of a certificate program in nursing management. PMID- 3097089 TI - Computer ease. Guidelines for selecting software. PMID- 3097090 TI - Teaching tips. Case history. PMID- 3097091 TI - Administrative angles. Developing the press release. PMID- 3097092 TI - Antimutagenic properties of lactic acid-cultured milk on chemical and fecal mutagens. AB - The antimutagenic properties of milk cultured with Lactobacillus bulgaricus and Streptococcus thermophilus were examined using streptomycin-dependent strains of Salmonella in an in vitro assay system. The mutagens utilized for testing included 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide, 4-nitroquinoline-N-oxide, and fecal mutagenic extracts from cats, monkeys, dogs, and other mammals. Both types of cultured milk exhibited antimutagenic activity on all mutagens used. Antimutagenic activities of the cultured milks with 2-(2-furyl)-3-(5-nitro-2 furyl) acrylamide and 4-nitroquinoline-N-oxide increased with incubation time but were thermolabile beyond 55 degrees C for 10 min. PMID- 3097093 TI - Use of ultraviolet energy to degrade aflatoxin M1 in raw or heated milk with and without added peroxide. AB - Raw whole milk was artificially contaminated to contain 1 ppb aflatoxin M1. A thin layer of milk (.1 cm) was irradiated with ultraviolet energy. In the first experiment, milk was held at 90 degrees C for 10 min, cooled to 20 degrees C, and irradiated for 30 min. Amount of aflatoxin M1 decreased equally (56.2 vs. 53.9%) in raw or preheated milk, suggesting no involvement of milk enzymes in degrading aflatoxin M1 by ultraviolet energy. Data obtained when raw milk containing aflatoxin M1 was exposed to ultraviolet energy for 15 to 60 min suggest first order kinetics for the degradation reaction. In another experiment, milk was held at 5, 25, or 65 degrees C while it was being irradiated. Aflatoxin M1 was degraded at all temperatures. Amount of toxin decreased nonlinearly when temperature at which milk was held was increased. Presence in milk of benzoyl peroxide at .002% did not change the extent to which aflatoxin M1 was degraded by irradiation. Amount of toxin, however, decreased by 89.1% in milk containing .05% H2O2 as compared with 60.7% for H2O2-free milk when both were exposed to ultraviolet irradiation for 20 min at 25 degrees C. PMID- 3097094 TI - Metronidazole concentrations in human plasma, saliva, and gingival crevice fluid after a single dose. AB - Metronidazole concentrations were estimated in four human volunteers after a single dose of 750 mg taken orally. Samples of blood, saliva, and gingival crevice fluid were collected before intake and during the following 24 hours. The concentrations of metronidazole in plasma and saliva were measured by high performance liquid chromatography (HPLC). The concentrations in gingival fluid were estimated by a capillary agar-diffusion assay. The results of the metronidazole measurements as obtained by both methods were significantly correlated. The peak concentrations of metronidazole in plasma and saliva were in the same range, 8.7-13.8 micrograms/mL, and similar concentrations were found in the gingival fluid samples. It is concluded that metronidazole taken orally has similar pharmacokinetics in both saliva and plasma, and that a single oral dose of 750 mg metronidazole leads to a concentration of the drug in the gingival crevice fluid that exceeds the minimal inhibitory concentration for most anaerobic oral micro-organisms. PMID- 3097095 TI - Interleukin-1 modulates T6 expression on a putative intra-epithelial Langerhans cell precursor population. AB - T6 is an antigen which is a highly specific marker for Langerhans cells. Previous studies have demonstrated that Interleukin-1 (IL-1) and an IL-1 inhibitor (ILS) modulate T6 expression (T6E) in explant culture. The present study examined the effects of IL-1 and ILS on T6E in dispersed gingival epithelial cell (EC) cultures. EC were obtained by trypsinization of gingival fragments obtained during periodontal surgery. T6E by EC was demonstrated using OKT6 monoclonal antibody in an immuno-peroxidase technique. In both unseparated and T6-depleted EC, IL-1 (0.5 U/mL) stimulated T6E, and this effect was abrogated by ILS (1:30). ILS alone depressed T6E in unseparated EC cultures. All effects were consistent between four- and 24-hour culture periods, and no treatment affected EC viability, thus excluding cell proliferation or necrosis as a vector for the action of IL-1 and ILS. These results indicate that a population of epithelial cells exists which is induced to express T6 under the influence of IL-1. IL-1 and ILS act in combination to regulate T6E on these precursor cells and on DR(-) Langerhans cells in gingival epithelium. PMID- 3097096 TI - National health expenditures. PMID- 3097097 TI - [Kelthane degradation in the soil by a P. aeruginosa BS827 strain containing plasmid pBS3]. PMID- 3097098 TI - [Derivatives of methylene diphosphonic acid as tumorotropic agents. The quantitative aspects]. PMID- 3097099 TI - Coronary thrombolysis with recombinant tissue-type plasminogen activator: patency rate and regional wall motion after 3 months. AB - In a double-blind, placebo-controlled, randomized trial the long-term (+/- 3 months) effects of intravenous administration of recombinant tissue-type plasminogen activator (rt-PA) versus placebo were compared in relation to left ventricular function, coronary patency rate and antigenicity in 28 patients with a first myocardial infarction. Patency rate of the infarct-related coronary artery at the end of the rt-PA/placebo infusion and after 3 months of medical treatment (including oral anticoagulant agents) was 86 and 71%, respectively, in the rt-PA group, and 21 and 58%, respectively, in the placebo group. Regional wall motion of the infarct-related area was quantitated with digital subtraction angiography. Intrapatient comparisons revealed significant improvement in regional wall motion after 3 months in both the rt-PA and placebo groups. The improvement in the rt-PA group was not significantly greater than that in the placebo group. Thirteen patients (10 with rt-PA and 3 with placebo) with persistent patency (both early and late) of the infarct-related coronary artery showed a significant improvement of both global and regional left ventricular function, while 8 patients (2 with rt-PA and 6 with placebo) with persistent occlusion showed no changes. Antibodies against rt-PA were not detected in serum 2 weeks after the infusion, which is indicative of the lack of antigenicity of rt PA and allows for its repeated administration. PMID- 3097100 TI - Pharmacology of thrombolytic drugs. AB - Streptokinase and urokinase have proved to be useful in a limited number of clinical conditions. Mainly because of the risk and unpredictability of bleeding with this first generation of thrombolytic agents, thrombolysis has not been ingrained in medical practice. In the interim, more fibrin-specific thrombolytic agents have been developed such as acylated streptokinase-human plasminogen complex, tissue-type plasminogen activator (t-PA) and single chain urokinase-type plasminogen activator (scu-PA or pro-urokinase). Only the latter two drugs do not induce major systemic fibrinogenolysis at thrombolytic effective doses. These two agents, obtained by recombinant techniques, as well as acylated streptokinase plasminogen complex are available for clinical investigations. The first results of systemic administration of recombinant tissue-type plasminogen activation (t PA) in patients with acute myocardial infarction were published and are promising. Continued experimentation with t-PA and pro-urokinase in evolving myocardial infarction and other thrombotic disorders is essential to better delineate their therapeutic index. PMID- 3097101 TI - Metabolic effects of dietary versus parenteral fructose. AB - Fructose has been considered as an alternative sweetener to sucrose because it results in less glycemia when given to normal subjects or to those with mild noninsulin-dependent diabetes mellitus. Oral fructose also results in efficient glycogen synthesis. However, multiple hepatotoxic effects have been reported following parenteral fructose administration. We have examined the effects of large oral fructose and glucose loads (4 g/kg) and of graded intravenous fructose doses (50-500 mg/kg) on hepatic metabolism and glycogen synthesis in normal, fasted rats. Fructose was absorbed more slowly than glucose when given by gavage (59% vs 91% absorbed in 120 min). Oral fructose administration resulted in greater liver and muscle glycogen synthesis, despite smaller increases in plasma glucose and insulin concentrations, than was found after oral glucose administration. Increases in percent glycogen synthase I (active form) occurred after both oral fructose and glucose loads (67% vs 115% increase). There was no evidence of hepatotoxicity even after a very large oral fructose load. When small (less than or equal to 125 mg/kg) iv doses of fructose were given, the portal vein fructose concentration remained less than or equal to that found after oral fructose administration (1.1 mM). The percent synthase I increased up to threefold, and there was no evidence of hepatotoxicity. Larger iv doses resulted in a fall in percent synthase I, an increase in percent phosphorylase a, and inorganic phosphate and nucleotide depletion. We conclude that the slow absorption of an oral fructose load prevents hepatotoxic effects and permits efficient glycogen synthesis. PMID- 3097102 TI - Diminished phospholipid incorporation of essential fatty acids in peripheral blood leucocytes from patients with Crohn's disease: correlation with zinc depletion. AB - Peripheral blood leucocytes from patients with Crohn's disease have been shown to have lower zinc content than those from a normal population. Since zinc influences essential fatty acid metabolism, incorporation of 14C-linoleic and 3H arachidonic acids was studied in peripheral blood leucocytes from controls and patients with Crohn's disease. The zinc content of the leucocytes was also measured. After incubation for 2 h, content of 3H-arachidonic acid, but not 14C linoleic acid, was greater in Crohn's disease leucocytes than in controls. In the Crohn's disease leucocytes, incorporation of both labelled fatty acids into the phosphatidylcholine fraction was significantly lower than in controls, whereas the amount of both fatty acids remaining in the leucocytes as free fatty acids was increased by 70%. In Crohn's disease, leucocyte zinc level was positively associated with the percentage of 3H-arachidonic acid incorporation into phosphatidylcholine. We conclude that peripheral blood leucocytes from patients with Crohn's disease have abnormal essential fatty acid metabolism and that 3H arachidonic acid incorporation into the phosphatidylcholine fraction of leucocyte lipids in Crohn's disease varies as the zinc content of the leucocytes. PMID- 3097103 TI - Optimized calcium/phosphorus solubility in a parenteral nutrition solution containing dicarboxylic amino acids and cysteine. AB - The solubility of calcium and phosphorus was studied in neonatal parenteral nutrition solutions containing dicarboxylic amino acids and cysteine. Experimental amino acid solutions containing aspartic acid, glutamic acid, and cysteine in concentrations from 0.5% to 2.0% were studied with dextrose concentrations of 5-20% plus standard electrolyte, vitamin, and trace element additives. Solutions were held at room temperature for 24 hr prior to incubation in a 37 degrees C water bath for 30 min. The pH of each solution was determined. Precipitation was detected by light scattering on a Cobas Bio centrifugal analyzer. An absorbance greater than 0.015 at 600 nm was considered evidence of precipitation. The pH of test solutions ranged between 5.7 and 6.4. Increasing amino acid concentration produced an improvement in calcium/phosphate solubility. Change in dextrose concentration had a lesser effect. Solutions of 10% dextrose with 2% amino acids contained 40 mEq/liter calcium and 17 mmol/liter phosphorus without precipitation. Administered at 150 ml/kg/day, such a solution would provide 120 mg/kg body weight/day calcium and 80 mg/kg/day phosphorus, approximately the daily in utero accretion rates during the last trimester. This is not readily achieved in comparable solutions of previous amino acid formulations. PMID- 3097104 TI - Determination of metabolically active B12 and inactive B12 analog titers in human blood using several microbial reagents and a radiodilution assay. AB - Metabolically active B12 analogs and inactive B12 analogs were measured in plasma, red blood cells (RBC), and pooled pernicious anemia serum. B12 values by Lactobacillus leichmannii, Escherichia coli, Euglena gracilis, and radioisotope dilution method (RIDA) as assays for total B12 (active analogs + inactive analogs) were compared to Ochromonas malhamensis values as index of only metabolically active B12. B12 values above those with O malhamensis distinguished inactive analogs from active B12. Inactive analogs contribute 85, 97, 135, and 163% above active B12 activity in normal plasma when E gracilis, L leichmannii, RIDA, and E coli, respectively, were used for B12 analysis. RIDA B12 determinations for active B12 in plasma showed that 44% of the B12 measured was still due to inactive analogs when compared to O malhamensis B12 activity. Inactive B12 analogs contributed 21, 151, and 224% above O malhamensis active B12 in RBC when E gracilis, L leichmannii, and E coli, respectively, were used. PMID- 3097105 TI - Dietary protein effects on cholesterol and lipoprotein concentrations: a review. AB - Different dietary proteins exert different effects on plasma cholesterol concentrations. Animal studies have shown that animal proteins, most notably casein, increase plasma total cholesterol concentrations compared with vegetable proteins, such as soy. Soy protein has been shown to be hypocholesterolemic in rats, swine, primates, and rabbits. Epidemiologic studies have disclosed that vegetarians have lower mean plasma cholesterol concentrations than populations consuming diets of mixed proteins, but it is unclear whether this effect results specifically from the animal or vegetable nature of the protein. In human clinical experiments, substituting soy protein for mixed protein reduces plasma total cholesterol concentration in hypercholesterolemic subjects, but it causes only a small, nonsignificant change in persons with normal plasma cholesterol concentrations. The mechanism responsible for the effects of different proteins on plasma cholesterol concentrations has not been established. One hypothesis suggests that animal proteins, which have a greater content of phosphorylated amino acids than vegetable proteins, interfere with bile acid reabsorption. Another hypothesis suggests that the amino acid content of the protein affects cholesterol absorption, tissue storage, synthesis, and excretion. The dietary protein may also alter cholesterol metabolism by affecting plasma hormone concentrations, either postprandially or over weeks to months. Among the hormones thought to be affected by dietary protein source are insulin, glucagon, and thyroid hormones. Gastrointestinal hormones, such as gastrointestinal inhibitory polypeptide, may also be affected by dietary protein. PMID- 3097106 TI - Effect of a high-dextrose diet on sucrase and lactase activity in jejunum of obese mice (C57BL/6J obob). AB - The activities of intestinal disaccharidases are known to be responsive to changes in the dietary intake of carbohydrates in the adult rat. Little is known, however, regarding the activities of these enzymes in obese subjects and how they are affected by differing carbohydrate intakes. To evaluate the effect of carbohydrate intake on the activity of intestinal disaccharidases in obesity, we used the genetically obese mouse C57BL/6J obob as an experimental model. Representing an example of early-onset obesity and mature-onset diabetes, this animal is characteristically hyperinsulinemic and hyperglycemic. Groups of obese mice and lean littermates were fed for 7 weeks equal amounts of either high dextrose or low-dextrose isoenergetic diets. Sucrase, maltase, and lactase activities were measured on intestinal homogenates from the proximal and middle portions of the jejunoileum (upper and lower jejunum). Results were expressed as activity per tissue protein as well as total activity. Obese mice were found to have consistently greater total activity of both sucrase and maltase than their lean littermates, mostly as a result of increased intestinal size. Total lactase activity, however, was similar in the upper jejunum in both obese and lean mice, largely related to a decreased specific activity in obese mice. All mice fed the high-dextrose diet had significantly increased total activity of all disaccharidases studied when compared to the low-dextrose-fed animals, except for the lactase activity in the lower jejunum, where no differences were found in either group. Increases in activity related to high carbohydrate intake were a result of increases in specific activity. PMID- 3097107 TI - Immunologic and biochemical properties of the major mouse urinary allergen (Mus m 1). AB - Rabbit antiserum to the mouse major urinary protein identified a single antigen that was also found in mouse serum and pelt extract. The skin test reactivity of mouse-pelt extract and mouse urine in two mouse-allergic subjects was significantly reduced after immunoabsorption with the gamma globulin fraction of this antiserum. The antigen defined by this antiserum was designated mouse allergen 1 (MA1). An immunoelectrophoretic procedure was set up to measure its concentration. MA1 had a molecular weight of approximately 19,000 on Sephadex gel filtration and 18,000 to 21,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Isoelectric focusing identified at least four bands with antigenic activity; the major band had an isoelectric point of 3.9. Significant antigenic and allergenic activity of MA1 was retained on reduction and digestion with papain and pepsin. Heating at 90 degrees C for periods up to 180 minutes resulted in a progressive loss, but not abolition, of activity. Serum and urine derived from male mice contained approximately fourfold more MA1 than samples derived from female mice. Urine contained at least 100-fold more MA1 than serum. Of the tissue extracts studied, liver extract had the highest amount of MA1. The immunochemical properties of MA1, its tissue distribution, and sex differences in its concentration provide strong evidence that MA1 is identical to the previously described mouse major urinary protein. PMID- 3097108 TI - Placebo-controlled double-blind food challenge in asthma. AB - To determine the prevalence of food allergy as a cause of exacerbation of asthma, we studied 300 consecutive patients with asthma (7 months to 80 years of age) who attended a respiratory clinic. Each patient was screened for possible food allergy by means of a questionnaire and by skin prick tests with the six food allergens most common in our area. Patients with either a suggestive history and/or a positive prick test and/or RAST underwent double-blind food challenge with lyophilized food in capsules or food mixed in a broth to disguise its taste. Pulmonary function tests and symptoms were followed for 8 hours after each challenge. Of the 300 patients screened, only 25 had either a history or skin prick tests or RAST responses suggestive of food allergy. Twenty patients had interpretable food challenges. In these 20 patients, food challenge caused asthma in six and caused other symptoms (atopic dermatitis and gastrointestinal symptoms) in five. On rechallenge after pretreatment with disodium cromoglycate (300 mg 30 minutes before the food challenge), the asthmatic response was blocked in four of five subjects. The patients with asthma with food allergy were generally young, had a current or past history of atopic dermatitis, and high total serum IgE levels. Our findings confirm that food allergy can elicit asthma, but its incidence is low, even in the population attending a specialty clinic. Food elimination diets should not be prescribed for all patients reporting an adverse reaction to foods or having a positive skin prick test and/or RAST with food allergens. In patients with asthma caused by food allergy, disodium cromoglycate may be used to complement elimination diets. PMID- 3097109 TI - The treatment of mild to severe chronic idiopathic urticaria with astemizole: double-blind and open trials. AB - Astemizole is a new H1 histamine-receptor antagonist that has a long elimination half-life and high H1-receptor affinity. This double-blind study evaluated the safety and efficacy of astemizole in the treatment of chronic idiopathic urticaria (more than or equal to 3 months). Seventeen male and 34 female adult patients with chronic idiopathic urticaria entered the 2-month study. After a 48- to 72-hour washout, half the subjects were prerandomized to receive astemizole (10 mg), and the other half received placebo. Placebo-treated patients who were unable to complete the full 8 weeks because of uncontrolled chronic urticaria symptoms were entered into a 2-month open astemizole trial. Treatment with astemizole, as measured at the end point of each patient's treatment and compared to placebo, resulted in significant improvement of pruritus, erythema, number of wheals, frequency of urticarial attacks, and control of urticaria (p less than or equal to 0.03). The overall response to astemizole was significantly better than for placebo, according to both the investigator's and the patient's global evaluations (p less than 0.01) and as indicated by dropouts caused by treatment failure with placebo (p = 0.005). Six of 26 (24%) of the placebo-treated patients in the double-blind study had good to excellent results on the basis of global assessments. Thirteen of 16 patients with placebo-treatment failures who received astemizole in the open trial improved significantly from baseline symptoms of pruritus, erythema, and number of wheals (p less than or equal to 0.05). No significant side effects were reported except mild sedation in three astemizole treated subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097110 TI - Enzyme profile and immunochemical characterization of Aspergillus fumigatus antigens. AB - We have compared the immunochemical characteristics of culture-filtrate antigens (Ag) from Aspergillus fumigatus extracted in our laboratory with commercially available Ags. A total of 20 different preparations were studied for protein and carbohydrate content, presence of endotoxins, mycotoxins, and hemolytic toxins. These extracts were analyzed by two-dimensional electrophoresis for protein components. The immunogenicity of the preparations was determined by rocket electrophoresis with rabbit anti-A. fumigatus sera and by agar gel diffusion with sera from patients with allergic bronchopulmonary aspergillosis, aspergilloma, and normal control subjects. In order to have dependable immunologic results, the Ags must be sufficiently pure and reproducible. Until such time as pure and standardized Ags are available, the crude Ags used should be characterized to the extent that adequate reproducibility between preparations can be ascertained. The enzyme profile of the Ag preparations provides a fair indication of the quality of antigenic components, and together with other immunochemical parameters, it will be of use in determining the suitability of the extracts in immunodiagnosis. Immunochemical results demonstrate that commercial Ags contain less proteins and carbohydrates and fewer enzymes than the homemade antigens. In addition, fewer patients demonstrated specific precipitins against commercial Ags than with homemade Ags. This study once again confirms the need for pure standardized Ags for studying the immunologic response in patients with Aspergillus-induced diseases. Until such preparations are readily available, partially purified or crude Ags with known immunochemical properties and enzyme profile may be the choice for immunodiagnosis. PMID- 3097111 TI - Advances in nutrition care of children with neoplastic diseases: a review of treatment, research, and application. AB - Within the last decade, significant advances have been made both in treating children with cancer and in providing proper nutrition support. Oncologic treatment and nutrition research and their application to the nutrition care of children with cancer are reviewed. Quality nutrition care is now possible because of an improved understanding of (a) the prevalence and significance of protein energy malnutrition (PEM) in high-risk groups, (b) the staging and assessment of nutritional status, and (c) the efficacy and limitations of nutrition support options. Nutrition staging, assessment, and support should be integrated into treatment protocols for children with neoplastic diseases. Common risk factors for the development of PEM have been identified from serial monitoring of newly diagnosed children with a variety of tumors. Certain tumor types and their treatment can be classified within either low or high nutritional risk groups. A comprehensive nutrition program (intense nutrition counseling, favorite nutritious foods) is preferred for low nutritional risk groups but is ineffective in preventing or reversing PEM in high-risk groups. For high-risk patients, central parenteral nutrition (CPN) is the method of choice as a relatively short term but important support measure that allows children to withstand long intervals of intense treatment during periods of growth and development. Current data suggest that bone marrow suppression may be attenuated and treatment tolerance improved with the use of CPN in selected children with advanced cancer (e.g., acute nonlymphocytic leukemia or advanced neuroblastoma). PMID- 3097112 TI - Microcalorimetric measurements on tissue cells attached to microcarriers in stirred suspension. AB - Vero cells growing on microcarriers in stirred suspension were observed calorimetrically using a vessel designed for use with the LKB 'BioActivity Monitor'. Rates of formation of carbon dioxide and lactate were followed in parallel. The results showed that the power and rate of lactate formation could be correlated to both cell number and amount of protein, while the rate of carbon dioxide formation was slightly better correlated to cell number. The power per cell was 27.4 +/- 2.1 pW. Only 33% of this power could be accounted for by the formation of lactate and carbon dioxide. PMID- 3097113 TI - Role of renal nerve activity, plasma catecholamines and plasma vasopressin in cardiovascular responses to intracisternal neurotoxins in the rabbit. AB - We have examined the acute (0-3 h) effect of intracisternally administered 5,7 dihydroxytryptamine (DHT) and 6-hydroxydopamine (6-OHDA) on blood pressure, heart rate, renal nerve activity, plasma adrenaline, plasma noradrenaline and plasma vasopressin in conscious rabbits. The increase in blood pressure seen following 5,7-DHT treatment was associated with increases in adrenaline and vasopressin levels and renal nerve activity throughout the response. The increase in blood pressure which followed 6-OHDA administration was associated with an increase in renal nerve activity alone. These findings indicate that the rise in blood pressure elicited by these drugs involves an increase in sympathetic nerve activity. The absence of a rise in vasopressin levels during the response to 6 OHDA suggests that the rise in blood pressure seen in these animals is due entirely to a bulbospinal sympathoexcitatory pathway. PMID- 3097114 TI - Effects of intravenous TRH on growth hormone and cortisol serum levels in children and adolescents with insulin dependent diabetes mellitus. AB - The effects of an iv thyrotropin releasing hormone (TRH) bolus on serum growth hormone (GH) and cortisol levels were evaluated in 59 children and adolescents with insulin dependent diabetes mellitus (IDDM) and in 24 healthy, age-matched control subjects. In the IDDM group GH baseline levels sharply rose within 30 min after TRH and successively normalized. On the contrary, TRH injection failed to affect GH serum concentrations in the control group. The GH increase after TRH in IDDM patients was positively correlated to age, but unrelated to other variables, such as sex, pubertal stage, duration of disease, glycemia, glycosylated hemoglobin, thyrotropin and T4 concentrations. Twenty-one out of 59 diabetics and only 1/24 controls exhibited a paradoxical GH response to TRH, arbitrarily defined as a precocious increase (within 30 min), of more than 100% with respect to the baseline value, associated with a GH peak greater than 10 ng/ml. Eighteen IDDM patients underwent a second TRH test 12 to 24 months later and substantially exhibited the same GH pattern documented the first time. The mechanism responsible for such anomalous GH responsiveness to TRH in IDDM is unclear. However, it cannot be attributed to a nonspecific stress reaction, as proven by the lack of a concomitant increase of cortisol serum levels in the same subjects. PMID- 3097115 TI - Derangement of pituitary gonadotropin release with different GnRH pulsatile patterns in chronic intravenous or subcutaneous delivery. AB - The efficacy of iv and sc chronic GnRH administration with different pulsatile patterns (15 micrograms every 90 min and 7.8 micrograms every 90 min with minor intermediate pulses of 2.3 micrograms every 22.2 min) by means of portable pumps were evaluated in a patient with primary hypothalamic amenorrhea. Observations of the amplitude and duration of the induced serum gonadotropin concentrations, of follicular growth (via ultrasound), and of ovarian steroids were made. Iv delivery of GnRH, 15 micrograms every 90 min, induced a normal menstrual cycle. Dividing this dose, as described above, giving it iv and sc, resulted in inappropriate gonadotropin secretion (overstimulation and desensitization, respectively) and arrest of follicular development. Sc delivery of 15 micrograms GnRH every 90 min resulted in an insufficient LH stimulation. PMID- 3097116 TI - [Bacteriostatic effect of lidocaine hydrochloride on measuring of alkaline phosphatase activity from Bacillus megaterium KM]. PMID- 3097117 TI - Schistosomiasis in an American medical investigator. AB - A 42-year-old American male researcher contracted schistosomiasis from environmental sources in the course of his observations on human behavior in Upper Egypt. After a long asymptomatic period, he developed various symptoms and Schistosoma haematobium was found in a urine examination. After treatment with Metrifonate, urine examination became negative. However, abdominal pain persisted and most diagnostic tests were negative. Colonoscopic examination and biopsy of the mucosa revealed schistosomiasis. Treatment with Praziquantel was thoroughly effective in clearing the persistent Schistosoma haematobium infection. It is necessary to maintain a high index of suspicion in cases of potential schistosomiasis. The availability of nontoxic treatment is discussed. PMID- 3097118 TI - Calmodulin in Paramecium tetraurelia: localization from the in vivo to the ultrastructural level. AB - Monospecific polyclonal antibodies against Paramecium tetraurelia calmodulin were prepared and labeled for calmodulin localization on different levels of resolution: by microinjection into living cells; with isolated cell surface complexes (cortices); on the ultrastructural level, using Lowicryl sections of non-permeabilized cells (with colloidal gold-protein A labeling of antibodies bound); or using permeabilized and gently fixed cells for incubation with peroxidase- or microperoxidase-tagged antibodies. Sites selectively labeled above cytoplasmic background largely coincided, irrespective of the method used, although sensitivity, resolution, and liability to redistribution of antigen were quite different. (The methodological diversification applied allowed for their mutual control.) Nonspecific binding can be largely excluded, since all these methods gave negative results with pre-immune sera. We reached the following conclusions on sites with selective calmodulin binding (above cytoplasmic background level) in P. tetraurelia cells. A pool of calmodulin co-localized with F-actin, not only in the cortex (including fibrous materials around ciliary basal bodies) but also around food vacuoles (phagosomes) and, to a lesser degree, around the buccal cavity. Trichocyst docking sites on the cell membrane, and coated pits also displayed calmodulin labeling, thus indicating the potential involvement of calmodulin in exo-endocytosis processes. Calmodulin was also enriched on membranes of compartments with presumable ion (possibly Ca2+) transport capacity, such as trichocysts and the osmoregulatory system. Not selectively labeled were nuclei, mitochondria, and some small lysosomal organelles (as identified in vivo by rhodamine 123 or acridine orange fluorescence, respectively). PMID- 3097119 TI - Immunohistochemical localization and characterization of a protein from the basolateral membrane of rat small intestine epithelium using monoclonal antibody GZ-1. AB - The proteins of the basolateral membrane (BLM) of small intestine epithelial cell in rat have been less precisely described than those of the microvillus membrane (MVM). To identify BLM-specific proteins, Balb/c mice were immunized with isolated intestinal epithelial cells and monoclonal antibodies (MAb) to their cell membrane, produced with the hybridoma technique. One of the MAb so obtained (GZ-1), a class 1 IgG, is specifically directed to a surface membrane protein of intestinal epithelium (GZ-1-Ag). The MAb served to characterize the protein as follows. Light microscopic immunohistochemical FITC labeling and, still more clearly, electron microscopic labeling with colloidal gold on Lowicryl sections of small intestinal tissue, show that the GZ-1-Ag occurs only in BLM of the absorptive cell and the goblet cell. It is not present in the MVM, the tight junction area, and probably in the desmosomal sections of the membrane. The crypt cells are more markedly labeled with GZ-1 than are the villus cells; the villus cells are also more clearly labeled from the duodenum to the ileum. Gross analysis of the position of the gold marker on the BLM indicates that GZ-1-Ag is probably integrated into the lipid bilayer. With immunoblotting (with HRP as marker), a single band of MW 42,000 D can be identified as the corresponding GZ-1 Ag from the protein band pattern obtained with SDS-PAGE from BLM isolated in the presence of protease inhibitors (PI). In BLM fractions isolated without protease inhibition, a band of MW 30,000 D can be labeled with GZ-1. These results are interpreted as follows: GZ-1-Ag is a protein of MW 42,000 D. On isolation of the BLM without PI, a piece of this protein is broken off by proteolysis. The larger piece of the molecule (30,000 D) is not accessible to the proteolytic enzyme owing to its localization in the BLM, and therefore remains intact (and recognizable by the Ab). The preferred position of the gold marker on the BLM is in agreement with this explanation. PMID- 3097120 TI - Ultrastructural localization of laminin in rat sensory ganglia. AB - We adapted immunocytochemical methods for localization of laminin to examine its disposition in neural tissue at the ultrastructural level. In dorsal root ganglia, laminin was found in basal laminae of the satellite and Schwann cells ensheathing neuronal perikarya and nerve fibers, respectively, and around blood vessels. Within the basal lamina, the immunostain was found in the lamina lucida and lamina densa. Occasional immunostained coated pits were identified in satellite and Schwann cells, but virtually no intracellular label was seen even in freeze-thawed/detergent-permeabilized specimens. In the perineurium, only the basal lamina of the inward-facing surface of the inner-most cell layer was usually stained. PMID- 3097122 TI - Administration of F(ab')2 fragments of monoclonal antibody to L3T4 inhibits humoral immunity in mice without depleting L3T4+ cells. AB - Treatment of mice with monoclonal antibody (MAb) to L3T4 blocks the humoral immune response to antigens administered when L3T4+ cells are depleted. To determine whether depletion of target cells is required to suppress immunity, we examined the effect of treatment with F(ab')2 fragments of anti-L3T4 on the response of BALB/c mice to immunization with bovine serum albumin (BSA) in complete Freund's adjuvant. Treatment with F(ab')2 fragments of anti-L3T4 every 2 days (1 mg i.p.) beginning at the time of immunization significantly inhibited production of anti-BSA antibodies without depleting target cells. A single injection of anti-L3T4 fragments at the time of immunization also significantly inhibited production of anti-BSA antibodies, but was not as effective as repeated administration of the MAb fragments (75% inhibition compared with 98% inhibition; p less than 0.05). Moreover, one injection of anti-L3T4 fragments stimulated a host immune response to the rat MAb, whereas sustained therapy with the anti-L3T4 fragments blocked this response. Surprisingly, low doses (less than or equal to 10 micrograms/mouse) of intact rat MAb to L3T4 also stimulated a host immune response to the MAb but, as previously reported, higher doses of intact MAb to L3T4 did not. These findings establish that depletion of L3T4+ cells is not required to suppress immunity with MAb to L3T4. They also indicate that the ability of rat MAb to L3T4 to block the immune response to itself is dose dependent. Because the L3T4 antigen in mice is homologous to the CD4 antigen in humans, our findings have implications regarding the potential use of MAb to CD4 in humans. PMID- 3097121 TI - Non-neonatal meningitis due to less common bacterial pathogens, the Netherlands, 1975-83. AB - In the Netherlands, case histories of 160 patients aged more than 1 month, with meningitis due to bacteria other than Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae were reviewed in order to look for associations between the bacteriological data and the course of disease. The incidence of such cases was about 0.8/100,000/year. Escherichia coli and Listeria monocytogenes each accounted for about 15% of the cases. The case-fatality rate was 18.8% (Gram-negative bacteria, 25%; Gram-positives, 15%) and sequelae occurred in 13.3% of the surviving patients (14 and 13% Gram-negative and Gram positive, respectively). Hearing loss was the most prevalent sequela (5.0%). Predisposing factors were present in 70% of patients (69 and 71% respectively), especially in meningitis due to enteric Gram-negative bacteria (except for salmonella) and due to staphylococci. Surveillance is important because the incidence of meningitis due to these micro-organisms is likely to increase and because the problems in antibiotic treatment have not yet been solved. PMID- 3097123 TI - Requirement for three distinct lymphokines for the induction of cytotoxic T lymphocytes from thymocytes. AB - The induction of cytotoxic T lymphocytes (CTL) from CTL precursors requires a combination of antigen and lymphokine signals. To investigate lymphokine requirements for CTL generation, we used an assay in which helper T cell and accessory cell-depleted spleen cells or whole thymocytes were cultured with lectin (Con A) and lymphokines. This culture was followed by assessment of lectin dependent cytolysis. High concentrations of recombinant interleukin 2 (R-IL 2) (100 U/ml) alone were not sufficient for lectin-mediated CTL induction from thymocytes, whereas 20 to 100 U/ml of R-IL 2 alone could induce a significant lectin-mediated CTL response from accessory cell-depleted spleen cells. Using thymocytes as responders, we found purified or recombinant interferon-gamma (IFN gamma) did not cause cytolytic activity either in the absence of or in the presence of R-IL 2. However, supernatant from Con A-stimulated rat spleen cells (rat Con A SN) in combination with R-IL 2 could induce cytolytic activity, suggesting that several factors are required for CTL induction. Con A SN was fractionated by gel filtration and the fractions were tested for ability to induce CTL. In the presence of a low level of R-IL 2 (5 U/ml), fractions with a Mr of approximately 31,000 could induce CTL, and this activity was referred to as CTL differentiation factor (CDF). The peak fractions containing CDF activity did not have detectable IL 1, IL 2, IFN-gamma, or CSF activity. However, by add-back experiments and the use of blocking antibodies, a monoclonal antibody against the IL 2 receptor or antibodies against murine IFN-gamma, we demonstrated that CTL induction from mature thymocytes (L3T4-, Lyt-2+) requires CDF activity in addition to IL 2 and IFN-gamma. PMID- 3097124 TI - Mitogenic effect of PMA + IL 2 on subpopulations of corticoresistant thymocytes. AB - The proliferative response of subpopulations of corticoresistant thymocytes (CRT) to phorbol-12-myristate-13-acetate (PMA) + interleukin 2 (IL 2) was investigated. Thymocyte subpopulations were selected by the indirect "panning" technique, and their purity was checked by cytofluorometry. Microcultures were set up with an optimal concentration of PMA, EL4 supernatant, or pure IL 2 obtained by recombinant DNA technology (r-IL 2) in the presence or in the absence of accessory splenic adherent cells (SAC). Under these conditions, only the Lyt-2+ CRT proliferated, and this response was IL 2-dose-dependent and was increased by accessory cells. When the calcium ionophore A23187 was added to the cultures, the proliferation of L3T4+ CRT was greatly increased. These results were confirmed by cultures at limiting dilution of positively selected Lyt-2+ and L3T4+ subpopulations of CRT at optimal concentrations of PMA, r-IL 2, A23187, and accessory cells. These results are consistent with the idea that two signals are necessary to activate L3T4+ CRT, whereas only IL 2 is necessary for PMA-induced proliferation of Lyt-2+ CRT. Finally, unlike the case of lectin-induced proliferation of Lyt-2+ and L3T4+ CRT, the presence of accessory cells or cell cell contact is important for optimal response to PMA + IL 2. PMID- 3097125 TI - Interferon-gamma suppresses B cell stimulation factor (BSF-1) induction of class II MHC determinants on B cells. AB - The data presented in this manuscript extend our previous observations that recombinant interferon-gamma (reIFN-gamma) can suppress anti-immunoglobulin (anti Ig)-stimulated B cell proliferation, and demonstrate that reIFN-gamma can also suppress B cell stimulation factor type 1 (BSF-1)-stimulated increases in expression of MHC class II molecules (Ia) on B cells. This suppression is most effective when relatively low concentrations of BSF-1 are employed, but is still very substantial even when optimal concentrations of BSF-1 were used. This suppression is also observed when size-separated small B cells which are devoid of detectable macrophages or NK cells are cultured with BSF-1 and reIFN-gamma, thus suggesting that IFN-gamma-mediated inhibition is a consequence of a direct effect on the B cells. Incubation of B cells with reIFN-gamma for 24 hr before their culture with BSF-1 did not prevent BSF-1-stimulated increases in sIa. This finding supports the contention that the effect of IFN-gamma is not mediated via the stimulation of "suppressor" influences in these cell cultures. The inhibition of B cell activation by IFN-gamma occurs within the first 3 hr after the onset of culture, as demonstrated by the inability of antibody to IFN-gamma to totally reverse the IFN-gamma-mediated suppressive effects on B cell proliferation if it is added later than 3 hr after the onset of culture. These results suggest a role for IFN-gamma in down-regulating the ability of B cells to function as antigen presenting cells in non-cognate T cell-dependent responses. PMID- 3097126 TI - Recombinant human interferon-gamma inhibits formation of human osteoclast-like cells. AB - Interferon-gamma (IFN-gamma) inhibits osteoclastic bone resorption in vitro, but the mechanism responsible for this inhibition is unknown. We have used a long term human marrow culture system that forms multinucleated cells (MNC) with osteoclast characteristics to test the effect of recombinant human IFN-gamma on MNC formation. The addition of 1,25-dihydroxy-vitamin D3 (1,25D3) at 10(-8) M to these cultures significantly increased both MNC formation and the number of nuclei per MNC. IFN-gamma at 100 U/ml strongly inhibited both of these effects of 1,25D3 in this system. IFN-gamma significantly inhibited MNC formation at very low concentrations (4 U/ml), with 10 U/ml inhibiting 1,25D3-stimulated MNC formation by 50%. In contrast, 100 U/ml of IFN-gamma were required to inhibit the growth of granulocyte-macrophage colony-forming cells, the probable progenitor for MNC, by 50%. Treatment of cultures with IFN-gamma for only the first or last week of culture significantly inhibited MNC formation stimulated by 1,25D3. Autoradiographic studies with [3H]thymidine showed that IFN-gamma did not inhibit proliferation of precursors for MNC. Additionally, IFN-gamma inhibited MNC formation stimulated by parathyroid hormone or interleukin 1. These results suggest that IFN-gamma inhibits MNC formation, and that IFN-gamma inhibits bone resorption in part by inhibiting osteoclast formation. PMID- 3097127 TI - Characterization of an anti-idiotypic T cell hybridoma involved in the regulation of the immune response to the P815 mastocytoma. AB - We report the isolation and characterization of a T cell hybridoma (A29) which secretes a factor that exhibits anti-idiotypic and immune-modulating characteristics. The A29 cell line is thought to represent the hybrid analog of the Ts2 suppressor cell population in the cascade regulating the immune response to the P815 tumor in DBA/2 mice. The putative TsF2 molecule is reactive with the monoclonal antibody B16G, shown previously by us to bind a public specificity of T suppressor factors (TsF). A29 TsF also exhibits specific binding to a TsF1 secreted by another T cell hybridoma, A10, which shows specificity for antigen from the P815 tumor (this has been described previously). A29 itself does not exhibit binding to P815 antigens. Affinity-purified material from A29 appears to share characteristics with A10 molecules in that the predominant material has an apparent m.w. of 70,000. Studies with calcium flux of A29 cells showed that they respond significantly and specifically on exposure to A10 TsF stimulus. We showed further that affinity-purified A29 TsF molecules can specifically suppress the in vitro generation of syngeneic CTL to the P815 tumor, and that panning of DBA/2 splenocytes over A29-TsF-coated plates renders cell populations capable of generating a higher in vitro CTL response to P815 than appropriately treated controls. PMID- 3097128 TI - Distinct signals are required for proliferation and lymphokine gene expression in murine T cell clones. AB - Experiments were performed to assess the capacity of lectin (Con A), ionomycin, phorbol ester (PMA), and recombinant IL 2 to mediate proliferation as well as the expression of cell surface IL 2 receptors, two lymphokine genes, IL 2 and IFN gamma, and the c-myc proto-oncogene in cloned T cell populations. Stimulation of T cell clones with recombinant IL 2 resulted in proliferation and sustained expression of the c-myc cellular proto-oncogene, but did not induce the expression of mRNA for the lymphokines IFN-gamma and IL 2. In contrast, stimulation of cloned T cells with lectin alone induced significant IFN-gamma and IL 2 mRNA expression, up-regulation of the number of cell surface IL 2 receptors, and transient c-myc expression. Ionomycin alone was not a sufficient signal for lymphokine mRNA induction. The phorbol ester PMA alone induced neither proliferation nor lymphokine gene expression but potentiated lectin and ionomycin mediated signals. We also performed experiments to examine whether the T cell response to extracellular stimuli was a function of the activation state of the cell. Reexposure of 48-hr antigen-activated cloned cells to identical stimuli revealed several differences. Low but significant levels of IFN-gamma mRNA were now also reinduced in activated clones cells in response to IL 2 or PMA alone. Activated cells were refractory to reinduction of IL 2 mRNA by any stimulus, which may reflect a physiologic mechanism to limit clonal expansion after antigenic stimulation. This could be partially reversed by restimulation with lectin in the presence of cycloheximide, suggesting a role for a labile protein repressor in the down-regulation of IL 2 mRNA expression. PMA alone induced an IL 2-independent proliferative response. We demonstrate that distinct signals are required for lymphokine gene expression vs cellular proliferation in cloned T lymphocyte populations, and that the capacity of extracellular stimuli to reinduce expression of lymphokine genes or to mediate cell proliferation is altered by prior activation. PMID- 3097129 TI - Molecular limitations on variable-gene junctional diversity. PMID- 3097130 TI - Early events in lymphocyte activation as defined by three new monoclonal antibodies. AB - Three new lymphocyte activation antigens are described whose kinetics of appearance place them very early in the activation pathway. The 78,000 dalton early antigen (Ea) 1 is present at low levels on resting lymphocytes, and its expression is enhanced twofold to threefold within 3 hr of stimulation. Ea2, a nondisulfide-bonded 86,000 and 73,000 dalton heterodimer, is first detectable 3 hr after activation and peaks by 9 hr. Its presence on all but a few cell lines, plus the variable association with a lower m.w. (28,000) structure, suggest that it may serve as a receptor for a growth factor. Neither Ea1 nor Ea2 are restricted to lymphocytes. The 31,000 dalton Ea3 antigen is induced only by PHA but not by other means of activation, and may pre-exist within the cell. The Ea3 antibody blocks PHA-induced but not OKT3-induced mitogenesis, suggesting differences in the pathways of activation by these two stimuli. These reagents, and OKT3, were used to define the cyclosporine A (CSA)-sensitive stage of lymphocyte activation. CSA blocks at a point before the biosynthesis of Ea1 and after that of T3/T cell receptor loss from the cell surface, at a point close to Ea2 biosynthesis. PMID- 3097131 TI - Regulation of human T lymphocyte mitogenesis by antibodies to CD3. AB - The inhibitory and mitogenic effects of anti-CD3 antibodies (anti-CD3) were examined in cultures of human peripheral blood T cells. Resting T cells required the presence of accessory cells (AC) or phorbol myristate acetate (PMA) to be stimulated by soluble anti-CD3 (OKT3 and 64.1). Anti-CD3 was unable to induce activation of AC-depleted T cells as determined by IL 2 receptor expression, IL 2 production, cell cycle analysis, or detectable DNA synthesis. Although T cell responses to PHA also required AC, far fewer were necessary to generate responses. Anti-CD3 inhibited PHA-stimulated T cell IL 2 production, IL 2 receptor expression and proliferation in partially AC-depleted cultures. Moreover, anti-CD3 was able to inhibit PHA responses when added to culture as late as 24 to 42 hr after the initiation of a 96-hr incubation. Increasing concentrations of PHA reduced the inhibitory effect of anti-CD3 on PHA-stimulated T cell proliferation, whereas IL 2 production remained suppressed. Anti-CD3 linked to Sepharose beads effectively inhibited PHA-stimulated T cell DNA synthesis, indicating that internalization of the CD3 molecule was not required for inhibition of PHA responses. Although inhibition of IL 2 production was a major effect of anti-CD3 in PHA-stimulated cultures, it was not the only apparent inhibitory effect because the addition of exogenous IL 2 could not prevent inhibition completely. Intact AC but not IL 1 also reduced anti-CD3-mediated inhibition of PHA responsiveness, whereas the addition of both IL 2 and AC largely prevented inhibition. Thus, anti-CD3 in the absence of adequate AC signals exerted a number of distinct inhibitory effects on mitogen-induced T cell activation. These results suggest that the CD3 molecular complex may play a role in regulating T cell responsiveness after engagement of the T cell receptor by a number of mechanisms, some of which involve inhibition of IL 2 production. PMID- 3097132 TI - Small bowel mucosa from celiac patients generates 15-hydroxyeicosatetraenoic acid (15-HETE) after in vitro challenge with gluten. AB - Celiac disease (gluten-sensitive enteropathy [GSE]) is a disorder characterized by small intestinal mucosal injury caused by dietary exposure to wheat gluten and similar proteins. There is evidence that the mucosal injury is immunologically mediated and there is an inflammatory infiltrate present in the mucosa. It is postulated that release of lipid-derived inflammatory mediators may be involved in the pathogenesis of the mucosal injury. Jejunal mucosal biopsy samples from patients with GSE and from a group of patients who were subsequently shown to have normal jejunal mucosa were incubated with tritiated arachidonate and a peptic/tryptic digest of either gluten or casein. Generation of lipid-derived inflammatory mediators was measured by beta-scintillation counting after separation of metabolites by reverse-phase high performance liquid chromatography with two different buffer systems. The predominant arachidonic acid metabolite generated was 15-hydroxyeicosatetraenoic acid (15-HETE). Mucosa from newly diagnosed GSE patients on a normal diet generated more 15-HETE than either control patients or GSE patients maintained on a gluten-free diet. In addition, gluten acted as a specific stimulus to 15-HETE production by mucosa from the GSE patients on a normal diet. 15-HETE has a number of biologic effects that could contribute to the mucosal changes seen in GSE, and the specific release of 15 HETE by gluten suggests involvement in the pathogenesis of the disorder. PMID- 3097133 TI - Interleukin 2 induction of interferon-gamma mRNA synthesis. AB - Interleukin 2 (IL 2) induces specific mRNA synthesis and secretion of an important immunoregulatory molecule, interferon-gamma (IFN-gamma). We have observed that treatment of an IL 2 independent murine T cell line, BUD-27, with IL 2, calcium ionophore A23187, or agents that activate phospholipid/Ca2+ dependent protein kinase C results in increased IFN-gamma mRNA transcription and release of anti-viral activity. These same agents each induced the subcellular redistribution of protein kinase C from cytosol to plasma membrane in both the BUD-27 cell line and its IL 2-dependent parent, CT6. Ionophore concentrations greater than 1 micron exhibited the most significant induction of IFN-gamma mRNA, which also correlated with the dose of ionophore, inducing translocation of protein kinase C. This correlation between increased mRNA levels and protein kinase C translocation suggests that a calcium-dependent event is involved in induction of IFN-gamma mRNA synthesis. Furthermore, the magnitude of the translocation of protein kinase C from cytosol to plasma membrane corresponded to the physiologic IL 2 dose-response for IFN-gamma secretion. The data suggest that the activation of protein kinase C and/or coordinate elevation of intracellular calcium may provide at least one mechanism of signal transduction for the regulation of IFN-gamma gene transcription. PMID- 3097134 TI - Human interferon-gamma acts as a B cell growth factor in the anti-IgM antibody co stimulatory assay but has no direct B cell differentiation activity. AB - In this study it is illustrated that recombinant human interferon-gamma (IFN gamma) acts as a B cell growth factor (BCGF) in the anti-IgM antibody co stimulatory assay. A monoclonal antibody that specifically inhibits the biological activities of IFN-gamma blocks its BCGF activity supporting the specificity of the IFN-gamma effect. Various IFN-gamma obtained from different sources displayed the same BCGF activity. Nonactivated B lymphocytes do not proliferate in response to IFN-gamma. IFN-gamma acts directly on B cells because highly purified B cells obtained after standard purification procedures coupled to cell sorting could still proliferate in response to IFN-gamma. Blood B lymphocytes were found to be more sensitive to the BCGF activity of IFN-gamma than B cells obtained from spleens or tonsils. The IFN-gamma-induced proliferation of B cells was short lasting when compared with that of recombinant IL 2 or BCGF containing T cell clone supernatants. B cells preactivated with either Staphylococcus aureus strain Cowan I (SAC) or optimal concentrations of anti-IgM antibodies coupled to beads did not proliferate in response to IFN gamma, whereas they proliferated in response to IL 2 or T cell clone supernatants. IFN-gamma did not stimulate nor inhibit the proliferative response of human B lymphocytes stimulated with optimal concentrations of anti-IgM antibodies or SAC. Additionally none of the different IFN-gamma tested had B cell differentiation factor activity in the standard SAC assay. These results indicate that IFN-gamma sensitizes B cells to suboptimal mitogenic concentrations of anti IgM antibody. PMID- 3097135 TI - Identification of monoclonal antibodies specific for the T cell receptor complex by Fc receptor-mediated CTL lysis. AB - Monoclonal antibodies (mAb) directed at the T cell receptor complex (TcR) on cloned T cells have generally been identified by their ability to inhibit the clone's antigen-specific function. Because such inhibition is highly dependent on antibody concentration and affinity, detection of anti-clonotypic antibodies to murine alloreactive T cells has been very difficult. In this report, an alternative method is described on the basis of the ability of antibodies specific for the TcR complex to activate T cells in an antigen-independent manner. The assay is based upon the observation that soluble antibodies to human T3 promote lysis of irrelevant, Fc receptor-positive targets by a human CTL line. By using this approach, an anti-TcR mAb has been identified among a panel of murine mAb generated against an alloreactive CTL clone. Induction of lysis by soluble anti-TcR mAb has been shown to require both the expression of Fc receptors on the target cell and conjugate formation between the effector and the target cell. This assay provides a screening procedure that is much more sensitive than inhibition of function, and it preferentially detects antibodies specific for cell surface molecules involved in T cell activation. PMID- 3097137 TI - The presence of antibody in mice chronically infected with Schistosoma mansoni which blocks in vitro killing of schistosomula. AB - We have previously reported that IgM monoclonal antibodies (mAb) that recognize surface carbohydrate determinants shared between schistosomula, cercariae, and miracidia block antibody/complement dependent killing of schistosomula in vitro. Binding assays that make use of one of the IgM mAb labeled with 125I demonstrated that serum from chronically infected mice (CMS) contained high levels of competing antibody, whereas serum from mice vaccinated with irradiated cercariae (VMS) contained little antibody of this specificity. Absorption of CMS with cercariae that removed antibodies to schistosomulum surface carbohydrate determinants increased its ability to kill schistosomula in vitro; absorption of VMS with cercariae failed to alter the lethal activity of the serum. Furthermore, fractionation of CMS by protein A Sepharose chromatography demonstrated that the IgG fraction had an increased lethal activity compared with unfractionated serum; this result was not seen with VMS. Finally, the IgM fraction of CMS was shown to block in vitro killing of the IgG fractions of both CMS and VMS. These data suggest that the blocking activities observed with the IgM mAb are contained within the serum of chronically infected mice but not in the serum of mice vaccinated with irradiated cercariae. PMID- 3097136 TI - The functional significance of the regulation of macrophage Ia expression by endogenous arachidonate metabolites in vitro. AB - We have examined the physiological effects of both exogenously and endogenously produced arachidonic acid metabolites on the expression of class II histocompatibility molecules in murine macrophages. This report shows that both a stable PGI2 analog and PGE2 are effective at suppressing lymphokine-stimulated Ia expression in vitro, whereas indomethacin and ibuprofen potentiate Ia expression, a stable TxA2 analog, TxB2, a thromboxane synthetase inhibitor, and LTC4 were ineffective on lymphokine-induced Ia expression in vitro, the suppression of Ia expression by PGI2 and PGE2 can be partially overcome by increasing the dose of lymphokine, a lymphokine supernatant capable of inducing Ia expression has no effect on the macrophage arachidonate enzyme activities, and the modulation of arachidonate metabolism during macrophage activation occurs differently in vitro than in vivo. PMID- 3097138 TI - Defective vaccine-induced resistance to Schistosoma mansoni in P strain mice. III. Specificity of the associated defect in cell-mediated immunity. AB - In contrast to many other strains, inbred P strain mice fail to develop significant levels of resistance to challenge Schistosoma mansoni infection as a result of prior vaccination with radiation-attenuated cercariae. In this study, the relationship between defects in resistance and development of cell-mediated immune reactivity was examined. Although splenocytes from immunized P mice demonstrated deficiencies in production of macrophage-activating lymphokine(s) in response to either antigenic or mitogenic stimulation, other aspects of T lymphocyte responsiveness including blastogenesis, production of interleukin 2, interleukin 3 and macrophage chemotactic factor, as well as helper cell function for secondary plaque-forming cell response to a T-dependent antigen and allospecific cytolytic T cell reactivity, appeared to be comparable with those of C57BL/6 mice, a strain that is protected by vaccination against S. mansoni. FACS comparison revealed no significant deficits in percentages of Thy-1+, Lyt-1+, or L3T4+ splenocytes in vaccinated P mice. The P-associated defect in production of macrophage-activating factor appeared to be at the level of the T cell rather than the antigen-presenting cell, because macrophages from P mice could reconstitute the lymphokine-producing capacity of T-enriched splenocytes from immunized, resistant (C57BL/6 X P) F1 or B10.P mice, whereas the converse was not true. These results indicate that vaccinated P mice have a selective defect in T cell function for production of macrophage-activating lymphokine, which is manifested as a failure to produce activated larvicidal macrophages at the site of specific antigen challenge in vivo and may be associated with the failure of this strain to become resistant to S. mansoni. PMID- 3097139 TI - Variable regions of antibodies to synthetic polypeptides. II. Analysis of variable region genes encoding antibodies specific for (T,G)-A--L. AB - Monoclonal antibodies specific for the synthetic polypeptide antigen (T,G)-A--L have been produced in two strains of mice, C57BL/10 and C3H.SW. The genes encoding the variable (V) regions of these antibodies have been studied by using the DNA hybridization technique of Southern, as well as by gene cloning and sequencing. Hybridization of DNA from 14 different cell lines with a kappa-chain probe revealed that the different cell lines used one of two different gene rearrangements to encode the recombined V region gene. There was a perfect correlation between light chain rearrangement, idiotype expression, and fine specificity. Hybridization analyses of the heavy chain revealed a more complex pattern. Seven hybridomas had the rearranged heavy chain V region genes on a 4.4 kb EcoRI restriction fragment. Others were found on restriction fragments that differed in length by several hundred base pairs. The recombined heavy chain V region genes were cloned from three different hybridoma cell lines secreting anti (T,G)-A--L antibodies, all of which express the same idiotype and fine specificity pattern. Restriction mapping and sequencing indicate that all three utilize the same V gene, identified as the 186-2 germline gene. However, different D and J genes are used to encode each of the antibodies. In contrast to the results seen in other antigen systems, heavy chain D and J genes do not have a major influence on idiotype expression and fine specificity of antibodies to the synthetic polypeptide (T,G)-A--L. PMID- 3097140 TI - Human monoclonal anti-T cell antibody from a patient with juvenile rheumatoid arthritis. AB - Antibody JRAI is a human monoclonal IgM antibody derived from a patient with juvenile rheumatoid arthritis that is cytotoxic to a subpopulation of normal T lymphocytes. JRAI recognizes approximately 80% of normal peripheral blood T cells, 90% of CD4+ cells, and 75% of CD8+ cells, as determined by complement mediated cytotoxicity. Within the CD8+ population, JRAI preferentially spares OKM1+ and Leu-11+ cells. These CD8+ cells retain suppressor-effector potential and show enriched natural killer cell activity. Within the CD4+ population, JRAI preferentially kills cells within the Leu-8+ subset, which contains suppressor inducer cells, and spares the Leu-8- subset, which contains the helpers for immunoglobulin synthesis. JRAI appears to recognize a previously undefined human lymphocyte surface molecule expressed differentially on phenotypically and functionally distinct subsets of human T cells. PMID- 3097141 TI - 2'Deoxycoformycin and deoxyadenosine affect IL 2 production and IL 2 receptor expression of human T cells. AB - Congenital deficiency of the enzyme adenosine deaminase (ADA) leads to severe combined immunodeficiency. 2'Deoxycoformycin (dCF), a tightly binding inhibitor of ADA, can induce the metabolic state of ADA deficiency. In vivo, the drug causes specific impairment of lymphocyte function and shows strong immunosuppressive properties. However, to decide whether inhibition of the enzyme ADA offers an attractive approach for immunosuppressive therapy, more information is needed about the immunologic mechanisms affected. In human T cells, we investigated the effect of dCF and deoxyadenosine (AdR) on cell activation, interleukin 2 (IL 2) production, and IL 2 receptor induction after allogeneic and lectin-induced stimulation. After allogeneic stimulation, dCF and AdR affected several events in T cellular immune response. Early events in T cell activation showed to be most sensitive to the drugs. Primary MLC was completely inhibited by concentrations as low as 1 microM dCF and 1 microM AdR. The addition of human recombinant IL 2 (rIL 2) could not abrogate the inhibitory effect of the drugs. Apart from activation of T cells, the drugs interfered with proliferation of activated T cells. Two events in activated T cells were affected: IL 2 production and IL 2 receptor expression. In secondary MLC, IL 2 production was markedly reduced in the presence of 9 microM dCF and 60 microM AdR. These concentrations appeared also to affect IL 2 receptor expression in 12-day primary MLC cells stimulated with rIL 2. Lectin stimulation was also affected by the drugs. In phytohemagglutinin (PHA)-stimulated cultures, 9 microM dCF and 60 microM AdR resulted in inhibition of proliferation and IL 2 receptor expression, whereas IL 2 production was normal. It is concluded that dCF and AdR interfere with several events in T cellular immune response such as cell activation, IL 2 production, and IL 2 receptor expression. According to these results, inhibition of the enzyme ADA seems an attractive approach to immunosuppressive therapy. PMID- 3097142 TI - Interleukin 2 responses of lpr and normal L3T4-/Lyt-2- T cells induced by TPA plus A23187. AB - The major population of cells that accumulate abnormally in MRL/Mp-lpr/lpr lymphoid tissue is Thy-1+, L3T4-, and Lyt-2-. To clarify the functional potential of these cells, we examined their proliferation, interleukin 2 (IL 2) receptor expression, and IL 2 secretion by using as stimulants the combination of 12-O tetradecanoylphorbol-2-acetate and A23187 (a calcium ionophore). Although the lpr T cells were capable of responding to these stimulants, the nature of the response and of the concentrations of ligand required differed sharply from the responses of normal adult T cells, and of adult L3T4-Lyt-2- thymocytes. There was a strong similarity but not identity when responses of 16 day fetal thymocytes were compared with those of lpr L3T4-Lyt-2- cells. The unusual functional properties of the lpr cells, such as high A23187 dose requirement for maximal proliferation, low percentage of IL 2 receptor-expressing cells, and low levels of IL 2 secretion, suggested that these cells are arrested at a stage of development similar to that of 16-day fetal thymocytes and before adult L3T4-/Lyt 2- thymocytes. PMID- 3097144 TI - Interleukin 2 receptors are expressed by alveolar macrophages during pulmonary sarcoidosis and are inducible by lymphokine treatment of normal human lung macrophages, blood monocytes, and monocyte cell lines. AB - Expression of receptors for IL 2 was believed initially to be restricted to T cells after their activation by IL 1 and antigen. However, recently IL 2 receptors (IL 2R) were demonstrated on activated B cells by using an anti-IL 2R monoclonal antibody (anti-Tac). In this study, we examined the capacity of cultured human alveolar macrophages, blood monocytes, and myelomonocytic (HL-60) or monoblast (U937) cell lines to bind three different anti-IL 2R monoclonal antibodies before or after stimulation with the monocyte-activating agents IFN gamma, LPS, phorbol ester, or lymphokine-containing conditioned medium. For each of the four cell populations examined, resting unstimulated cells bound little or no anti-IL 2R antibody, as shown independently by quantitative cell binding assay and by immunoperoxidase labeling. By contrast, incubation with recombinant IFN gamma, conditioned medium, or to a lesser extent, native or recombinant IL 2 itself, resulted in a significant enhancement of anti-IL 2 receptor monoclonal antibody binding by all four populations, whereas LPS, PMA, or IL 1 had no effect. In addition, membrane binding of anti-Tac antibody, similar to that seen after stimulation of normal lung macrophages with IFN-gamma, was detected by using macrophages obtained by bronchoalveolar lavage of five patients with active pulmonary sarcoidosis. These findings are consistent with the expression of a functional IL 2R on activated cells of the monocyte lineage, since anti-Tac binding to IFN-gamma-treated HL-60 cells was inhibited by addition of excess IL 2; specific binding of anti-IL 2 monoclonal antibodies was detected in the presence of exogenous IL 2; and a 50 to 55 kD molecule was immunoprecipitated from both activated lung macrophages and T lymphoblasts by using anti-Tac antibody. We conclude that human mononuclear phagocytes can be induced by lymphokines to express IL 2R, and that such IL 2R+ macrophages can be detected in vivo during inflammation. PMID- 3097143 TI - Identification of IL 2R+ T cells and macrophages within rejecting rat cardiac allografts, and comparison of the effects of treatment with anti-IL 2R monoclonal antibody or cyclosporin. AB - Monoclonal antibodies to lymphokine-induced activation antigens of lymphocytes and macrophages were used to analyze the intragraft events occurring during acute rejection of rat heterotopic cardiac allografts. The cells present during untreated rejection were then compared with those present in situ after immunosuppression with the mouse anti-rat IL 2 receptor (anti-IL 2R) monoclonal antibody ART-18 or cyclosporin (CsA). Untreated rats rejected their grafts within 7 days, whereas rats receiving 10 days of i.v. ART-18 antibody therapy showed graft prolongation to more than 21 days, and rats receiving CsA for 7 days maintained their grafts indefinitely. Untreated rejection was associated with an influx of T (W3/13+) cells and macrophages (ED-1+, ED-2+). Activated mononuclear cells (IL 2R+) were identified within rejecting grafts from day 2, and their numbers peaked on days 4 to 6 when 15 to 20% of infiltrating leukocytes were IL 2R+. Double labeling studies of IL 2R+ cells present at day 6 showed surprisingly that both T cells and macrophages expressed IL 2R. In particular, although 55.8 +/- 6.9% (mean +/- SD) of IL 2R+ cells expressed the pan-T cell antigen 3/13, a similar proportion of IL 2R+ cells (49.8 +/- 8.2%) expressed the macrophage antigen ED-2. Conversely, both T cells and macrophage populations showed heterogeneity in their expression of IL 2R, because 39.2 +/- 12.2% of T cells and 31.0 +/- 13.4% of macrophages were IL 2R+. In addition, inflammatory macrophages at day 6 expressed the A1-3 antigen. Expression of this antigen by macrophages has previously been linked with development of macrophage procoagulant activity, and in this model intragraft inflammatory macrophages were closely associated with widespread deposits of fibrin. By comparison with untreated animals, rats treated with either ART-18 or CsA both lacked detectable IL 2R+ cells during the first 14 days post-transplantation (post-Tx), and showed significantly less cellular infiltration. However, although grafts of CsA-treated animals continued to remain IL 2R- and failed to stain with the macrophage activation marker A1-3, ART-18-treated rats showed increasing infiltration by both IL 2R+ mononuclear cells and A1-3+ macrophages, as well as increasing perivascular and interstitial fibrin deposition, prior to rejection by day 22. These studies document the presence of small number of activated intragraft T cells and macrophages during rat cardiac rejection, and show how CsA, and to a lesser extent anti-IL 2R therapy, inhibit this in situ activation and prolong graft survival. (ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3097145 TI - Soluble interleukin 2 receptors are released by long term-cultured insulin specific T cells transiently after contact with antigen. AB - An enzyme-linked immunosorbent assay was used to quantitate soluble interleukin 2 receptors (IL 2R) released by antigen-dependent, insulin-specific murine T cells into the culture supernatant, as well as cell-associated IL 2R present in cell lysates. IL 2R were released solely after T cell activation by antigen. The release of IL 2R was transient, reaching optimal levels within 72 hr after antigen challenge and gradually declining to background levels thereafter, when the cells were subcultured in IL 2-enriched medium. The decrease in the amount of IL 2R released during culture in IL 2-containing medium paralleled the decrement in cellular IL 2R detected in cell lysates, in cell surface-expressed IL 2R as determined by cytofluorometry, as well as in high-affinity IL 2R. In contrast, IL 2R were constitutively released by an IL 2-dependent T cell clone. Soluble IL 2R might exert an immunoregulatory function by competing with cellular IL 2R for IL 2 binding. PMID- 3097146 TI - Spontaneous production of a suppressor factor by a human macrophage-like cell line U937. II. Suppression of antigen- and mitogen-induced blastogenesis, IL 2 production and IL 2 receptor expression in T lymphocytes. AB - U937, a human macrophage-like cell line, spontaneously produces a factor which inhibited blastogenic responses of human blood T lymphocytes stimulated with tuberculin-purified protein derivative (PPD) or phytohemagglutinin (PHA). We investigated the mechanism of suppressor action of the U937 factor. The U937 suppressor factor inhibited interleukin 2 (IL 2) production by human blood T lymphocytes stimulated with PPD or PHA. IL 1 did not overcome the inhibitory action of the U937 factor on PPD-induced IL 2 production by human blood T lymphocytes. The U937 factor also inhibited the production of IL 2 by a human leukemic cell line, JURKAT, stimulated with PHA. The U937 suppressor factor interfered with the expression of Tac antigen (IL 2 receptor) on PPD- or PHA stimulated blood T lymphocytes. The inhibitory activity of the U937 factor on Tac expression was not affected by the addition of IL 2 or a crude lymphokine containing T cell supernatant. Tac expression was more sensitive than IL 2 production to inhibition by U937-conditioned medium. The U937 suppressor factor was precipitable by 33 to 67% saturated ammonium sulfate and was inactivated at pH 2 or pH 11. Sephacryl S-200 Gel filtration analysis of U937 culture supernatants revealed that the inhibitory activities for blastogenesis, IL 2 production, and Tac expression co-purified in fractions with an apparent m.w. between 67,000 and 130,000. These data indicate that U937 spontaneously produces a macromolecular suppressive factor with major locus of action on the production of IL 2 and the expression of the IL 2 receptor. PMID- 3097147 TI - Prolactin-dependent mitogenesis in Nb 2 node lymphoma cells: effects of immunosuppressive cyclopeptides. AB - Prolactin (PRL)-stimulated ornithine decarboxylase (ODC) activity and subsequent proliferation are inhibited by the cyclopeptides cyclosporine (CsA) and didemnin B (DB) in Nb 2 node lymphoma cells. Similar concentrations of these agents also inhibit 125I-PRL binding, suggesting that their inhibitory effects on these PRL dependent physiologic responses are mediated at least in part at the level of PRL receptor interactions. The phorbol ester TPA stimulated ODC activity and [3H]thymidine incorporation to 54% and 31% that of a near-optimal mitogenic concentration of PRL (10 ng/ml), suggesting that mitogenesis in these cells is coupled to some degree to the activation of protein kinase C (PKC). The calcium ionophore A23187 increased ODC activity only slightly and actually decreased [3H]thymidine incorporation to a value below the "cells only" controls. The addition of TPA plus A23187 did not further enhance the effects of TPA to elevate ODC activity and [3H]thymidine incorporation. However, A23187 significantly elevated PRL-stimulated ODC activity with a subsequent inhibition of [3H]thymidine incorporation, suggesting a block of entry into S phase. Both cyclopeptides decreased the elevation of ODC activity in G1 phase of cell cycle in response to PRL, suggestive of a site of action for these agents in early G1, a conclusion compatible with their ability to inhibit PRL binding to these cells. Addition of CsA or DB 2 hr after PRL had no effect on PRL-stimulated ODC activity detectable at 6 hr, but addition of either as late as 6 hr still affected the extent of mitogenesis. This is in line with the requirement for PRL to be present in the culture medium for a minimum of 3 to 6 hr to invoke a maximal effect on mitogenesis. Addition of either cyclopeptide after the cells were in S phase had no effect on the extent of [3H]thymidine incorporation. An inhibitor of the cyclooxygenase pathway (indomethacin) enhanced both PRL-stimulated ODC activity and proliferation, whereas inhibition of the lipoxygenase pathway by NDGA attenuated only proliferation, suggesting that in Nb 2 cells, products of the lipoxygenase pathway may contribute to the mechanism of PRL-stimulated mitogenesis. Because Nb 2 lymphoma cells were derived from estrogenized rats, estrogen was tested as a mitogen. By itself it was not mitogenic, but in conjunction with PRL, estradiol-17 beta elevated the ODC response and inhibited proliferation. Inhibitors of PKC known to have minimal effects on RNA synthesis, quercetin and gossypol, totally inhibited both the elevations of ODC activity and [3H]thymidine incorporation in response to PRL in Nb 2 lymphoma cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3097148 TI - The kinetics of emergence and loss of mediator T lymphocytes acquired in response to infection with Mycobacterium tuberculosis. AB - Mice infected i.v. with the virulent Erdman strain of Mycobacterium tuberculosis exhibited three distinct phases of infection within the spleen. These consisted of a primary phase, characterized by the progressive growth of the organism; a secondary phase, in which the viable organism was progressively eliminated; and a tertiary phase, characterized by a chronic or slowly recrudescing disease state. Passive transfer experiments, in which T cell-enriched spleen cells from immune donors were infused into T cell-deficient recipients and were measured for their capacity to adoptively protect these mice from challenge with M. tuberculosis, provided evidence that at least three separate populations of protective T cells were acquired in response to the infection within the time frame of the experiments. These populations of T cells could be distinguished in that they differed in their expression of the L3T4 and Lyt-2 cell surface molecules, in terms of their kinetic profiles of emergence and loss, and (c) in terms of their susceptibility to cyclophosphamide. The results may suggest that different populations of protective T cells can be generated at different times during the infection as various classes of antigens (for example, metabolic or structural antigens) become available for presentation by host macrophages. It is hypothesized, furthermore, that the kinetics of emergence and loss of these various populations may reflect switching in the mode of immunity being expressed, particularly during the chronic phase of the infection, from that of a state of active immunity to one of immunologic memory. PMID- 3097149 TI - Novel V genes encode virtually identical variable regions of six murine monoclonal anti-bromelain-treated red blood cell autoantibodies. AB - The variable (V) region sequences of six immunoglobulin M (IgM, kappa) monoclonal autoantibodies that recognize bromelinized isologous red blood cells, obtained by fusions of peritoneal cells from NZB or CBA/J nonimmunized mice with BALB/c myeloma cells, were determined by direct mRNA sequencing. The V regions of the light chains (VL) are almost identical with one another, as are the V regions of the heavy chains (VH), which, however, differ by six linked-base substitutions, depending on the strain of mice producing the autoantibodies. Such variations may reflect allelic differences. The VH segments determined have no obvious correspondence to any VH genes identified so far. They may belong to the small VH group 4, where 73% homology, at the most, can be calculated at the protein level for codons 1 to 94. Alternatively, the VH regions may be members of a new group of VH sequences not previously found. The V kappa regions appear closely homologous to members of the V kappa-9 subgroup of myeloma proteins of unknown antigen-binding specificity. The joining segments, J kappa and JH, used by the autoantibodies investigated, originate from the J kappa 2 and JH1 germ-line gene segments, respectively. The nine base-long diversity segments, D, derive from one member of the germ-line D gene SP2 family. PMID- 3097150 TI - Antigen-presenting T cells. II. Clonal responses of alloreactive and virus specific self-restricted human cytotoxic T cell responses stimulated by T lymphoblasts. AB - The capacity of various stimulator cell types to present alloantigens or viral antigens to resting human CD8+ cytotoxic lymphocyte precursors (CLP) was analyzed in a limiting dilution culture system. Cell sorter-separated T lymphoblasts of both CD4+ and CD8+ phenotypes but not resting T cells were found to efficiently stimulate the clonal development of allogeneic CD8+ CLP. Thus, 5000 CD4+ T lymphoblasts activated as many (one out of 200 to one out of 300) allogeneic CLP as 50,000 peripheral blood mononuclear stimulator cells. This potent stimulator activity was found in CD4+ and CD8+ T lymphoblasts activated by mitogen, anti-T3 monoclonal antibody, or mixed leukocyte reactions. Cytotoxic T cells generated in this system were highly specific for HLA class I antigens. Furthermore, T lymphoblasts infected with mumps virus efficiently induced development of autologous CLP into CTL clones that were virus specific and self-HLA restricted, as shown by split-well analysis. The possible in vivo significance of antigen presenting T lymphoblasts is discussed. PMID- 3097151 TI - Amplification of human B cell activation by a monoclonal antibody to the B cell specific antigen CD22, Bp 130/140. AB - The B cell-specific antigen CD22 is a 130/140-Kd complex and is unique among human B cell antigens, since its surface expression is restricted to a subpopulation of Ig+ B cells. Here the function of the CD22 antigen was evaluated by using the mAb HD6, directed against one of the epitopes on the molecule. The HD6 antibody was constimulatory with anti-Ig in inducing small, dense tonsillar cells to proliferate; however, the antibody by itself was devoid of stimulatory activity. Anti-CD22 antibody also induced more anti-Ig-treated B cells to leave G0 and enter the G1 phase of the cell cycle. It also was constimulatory with low m.w. BCGF and with an antibody to a 50-Kd polypeptide, Bp50, which mediates a BCGF-like activity. Results of kinetic experiments and analysis of different B cell fractions suggested that anti-CD22 acts during an early phase of B cell activation, probably by amplifying the anti-Ig signal. F(ab')2 fragments of anti CD22 HD6 were as effective as the whole antibody in inducing augmentation of B cell proliferation, showing that the Fc portion of the molecule was not required for the activity. The results of these experiments, together with the intriguing distribution of the Bp 130/140 antigen in B cell ontogeny, suggest that this molecule plays an important role in the process that leads to B cell activation and proliferation. PMID- 3097152 TI - An enzyme immunoassay for osteocalcin. AB - A sensitive and specific enzyme immunoassay for bovine osteocalcin was developed with the use of enzyme-labeled antigen. Bovine osteocalcin was conjugated with beta-D-galactosidase for use in the immunoassay. The minimum amount of osteocalcin detectable by this method was 5-10 pg/assay. The enzyme immunoassay could detect immunoreactive osteocalcin levels in normal human sera, giving a value of 6.58 +/- 0.72 ng/ml (mean +/- SE of 16 human subjects). The correlation coefficient between the levels measured by this method and radioimmunoassay was 0.94. PMID- 3097153 TI - Stimulation of resting normal human peripheral blood mononuclear cells by fetal calf sera. Activation to an interleukin-2 responsive state. AB - Normal adult human peripheral blood mononuclear cells which are negative for interleukin-2 (IL-2) receptors as assessed by flow cytofluorometry, acquire IL-2 receptors and IL-2 responsiveness after culture in media supplemented with fetal calf sera. Thus, in the absence of any known external stimuli, fetal calf sera used to supplement culture media can induce the transformation of resting (G0) peripheral blood mononuclear cells to an activated (G1) state. The activated (G1) cells are able to progress through the rest of the cell cycle (S, G2, M) in the presence of IL-2. As a result, studies of human peripheral blood mononuclear cells in fetal calf serum-supplemented culture media should be interpreted with appropriate caution. PMID- 3097154 TI - Production of monoclonal antibodies against human growth hormone releasing hormone and their use in an enzyme-linked immunosorbent assay (ELISA) AB - Two murine monoclonal antibodies (mAbs) specific for human growth hormone releasing hormone (GHRH-44-NH2) were produced from a fusion of spleen cells from a BALB/c mouse immunized with GHRH-conjugated BSA with SP 2/0 myeloma cells. The antibodies were of the IgG1 kappa, and IgG2b-kappa isotypes. The binding of both antibodies to GHRH-coated plates was inhibited by a 30-44 amino acid fragment but not by a 1-26 fragment. Thus, both antibodies are directed against the carboxy terminus of the peptide. Furthermore, both antibodies bind to the same epitope on the 30-44 amino acid portion since they cross-inhibit each other's binding to intact GHRH. Using these mAbs, a direct binding GHRH enzyme-linked immunosorbent assay (ELISA) was developed which had a least detectable dose of 30 pg. The availability of these antibodies and their use in ELISA methodology permits consistent and specific detection of GHRH in a non-isotope assay. They should prove of value in screening acromegalic patients for ectopic sources of GHRH secretion and in studies of ontogenic analysis of GHRH production. PMID- 3097155 TI - 'Key paper' for covalent binding of proteins and its uses. AB - A simple method for covalent coupling of proteins to filter paper modified with quinone groups is described. This paper, termed 'Key paper' is flexible, stable on storage and does not require any activation before use. Proteins bound to Key paper can be detected by enzyme immunoassay, radioimmunoassay or Coomassie blue staining. Bound enzymes retain their enzymatic activity. Nucleic acids do not bind and do not interfere with the activity of the bound proteins. Because of its mechanical and chemical properties Key paper is a good matrix for electroblotting and for direct in situ analysis of proteins. PMID- 3097156 TI - An ELISA for IgM titer of human serum. AB - An ELISA for the measurement of serum immunoglobulins (Ig) of specific isotype is described which is reproducible, more sensitive than currently used methods and simple to perform. Data are presented to support the need to include a reference serum of known Ig content on the same plate as the specimen sera in order to compensate for plate-to-plate variability due to ambient conditions. This method should prove useful for monitoring changes in levels of specific Ig classes in the progression of diseases with immune system involvement or during a therapeutic regimen. PMID- 3097157 TI - A comparison of two fluorescence-activated cell sorters, the FACSIV (laser) and the FACSTm (mercury lamp), as research analyzers for the quantification of T and B cell subsets in human peripheral blood. AB - T cell subset determinations were performed on 146 peripheral blood samples from healthy volunteers, and on 112 samples from immune deficient patients using two fluorescence-activated cell sorters (the FACSIV laser, and the FACSTm mercury lamp analyzer). The procedures necessary for the use and calibration of the FACSTm analyzer are discussed, and detailed. Using the FACSTm analyzer, counts were made of T and B cell subsets in 28 patients with multiple infections, 9 patients suffering from the acquired immune deficiency syndrome (AIDS) and 16 patients with a primary immunodeficiency disease. These results were compared with data obtained from 47 healthy volunteers, as control references. Results from the two instruments proved closely comparable, both qualitatively and quantitatively. PMID- 3097158 TI - A quantitative in vitro assay of polymorphonuclear leukocyte migration through human amnion membrane utilizing 111in-oxine. AB - A modified amnion chemotaxis assay is described for measurement of polymorphonuclear leukocyte(s) (PMNL) migration (random and directed) into a viable membrane. The primary modifications are the use of 111In-oxine-labelled PMNL and replacement of the nitrocellulose 'trap' filter with a type I collagen sponge. The modifications resulted in four important benefits: the quantification of PMNL migration was simplified; reader subjectivity was eliminated; the information gained of the migration process was enhanced; and the assay time was decreased. The amnion chemotaxis assay with the modifications reported should provide the means of evaluating several aspects of the inflammatory response of PMNL. PMID- 3097159 TI - A quantitative study of the effect of terfenadine on cutaneous erythema induced by UVB and UVC radiation. AB - Terfenadine, given in sufficient dose to cause maximum H1 receptor blockade, had no effect on the intensity of UVB or UVC erythema measured with a reflectance instrument at 4, 8, and 24 h after irradiation. Histamine, acting on the H1 receptor, is not a significant mediator of UVB or UVC erythema. PMID- 3097160 TI - Reactogenicity and immunogenicity of a quadrivalent combined meningococcal polysaccharide vaccine in children. PMID- 3097161 TI - Ceftazidime resistance in Pseudomonas aeruginosa: transduction by a wild-type phage. PMID- 3097163 TI - [Aneurysm of a diverticulum of the ductus arteriosus in an adult: a case report]. AB - An aenurysm of a diverticulum of the ductus arteriosus in a 33-year-old man was presented. The chest radiography revealed a mass obscurring the aortic window above the hilus of the left lung. His blood pressure was 130/70 mmHg, and there was no difference in pressures between the upper and lower or between the right and left extremities. A CT scan of the chest showed 30 X 34 mm angioma adjacent to the descending aorta and pulmonary artery. Aortography and contrast radiography of the right ventricle revealed a cystic pedunculated aneurysm at the superior portion of the descending aorta. The base of the left pulmonary artery was slightly displaced. There was no communication between the aorta and pulmonary artery, nor was any significant difference in pressure between the ascending and descending aorta. This case was diagnosed as an aneurysm of the diverticulum of the ductus arteriosus, and then it was resected. The abnormality was confirmed by the localization of the aneurysm and histopathologic findings, but the presence of the ligamentum arteriosum was not confirmed. This is the 23rd case of the aneurysm of the diverticulum of the ductus arteriosus in adults, and the first case in Japan in which the diagnosis was made in a living patient, followed by successful surgery. PMID- 3097162 TI - Acidification of phagosomes in murine macrophages: blockage by Nocardia asteroides. AB - Most strains of Nocardia asteroides are susceptible to the detrimental effects of pH 5 when grown in buffered brain-heart infusion broth. Preventing phagosomal acidification may be a mechanism by which this organism survives the microbicidal activity of macrophages. Fluorescein isothiocyanate was conjugated to the surface of Nocardia and Saccharomyces to form pH-sensitive fluorescent probes. The fluorescent emission, and thus the pH, of this probe was quantitated within individual phagosomes by using a computerized cytospectrophotometer. When either live or dead cells of virulent N. asteroides strain GUH-2 were ingested, the phagosomal pH remained above pH 7 for 2 hr. A nonpathogenic soil isolate, N. asteroides strain 19247, only partially blocked acidification. In contrast, when Saccharomyces was used as a control for normal response, the pH decreased to approximately pH 5. Therefore, virulent N. asteroides blocks phagosomal acidification. Because killed Nocardia act in the same manner, this inhibition of acidification appears to be associated with cellular components. This capacity to prevent phagosomal acidification may be prerequisite to the survival of intracellular pathogens. PMID- 3097164 TI - [Effects of nitroglycerin on left ventricular geometry and compliance in man]. AB - The effects of nitroglycerin (NTG) on relaxation characteristics of the infarcted and non-infarcted myocardium were investigated by calculating a segment length on the epicardium of the left ventricle for 16 patients with old myocardial infarction. The spatial segment length was measured between two points which were identified as a junction of ramifying branches of the left coronary arteries using biplane coronary cineangiography. Regional myocardial stiffness was expressed as delta P/delta L, where delta P was an increment of left ventricular (LV) diastolic pressure from the lowest LV diastolic pressure to the pressure at the maximal segment length, and delta L was the difference of two segment lengths corresponding to those pressures. Myocardial stiffness decreased from 0.0402 +/- 0.0293 mmHg/mm to 0.0212 +/- 0.0157 with intracoronary NTG (p less than 0.01) and from 0.0220 +/- 0.0090 to 0.0136 +/- 0.0124 with sublingual NTG (p less than 0.001) in the non-infarcted portions. However, it was unchanged with both intracoronary and sublingual NTG in the infarcted portions. NTG may cause venous pooling and may decrease diastolic wall tension of the left ventricle as its indirect effect on the non-infarcted myocardium. Also, the non-infarcted myocardium may be influenced by dilatation of the epicardial coronary artery. Muscle stiffness of the infarcted myocardium was unchanged, probably due to the rigidity of myocardial fibrosis. It was concluded that in myocardial infarction diastolic distensibility of the non-infarcted portion can be improved by NTG both through indirect and direct effects. PMID- 3097165 TI - On a piroplasm of the genus Dactylosoma Labbe, 1894 (Dactylosomatidae: Piroplasmorida) in Bufo dhufarensis from Saudi Arabia. PMID- 3097166 TI - Evaluation of praziquantel efficiency in the treatment of schistosomiasis. PMID- 3097167 TI - The host-parasite response to Schistosoma mansoni infection in experimental animals. PMID- 3097168 TI - Correlation between circumoval precipitin test and intensity of infection in intestinal schistosomiasis. PMID- 3097169 TI - Study of leukocyturia and bacteriuria among patients with urinary bilharziasis. PMID- 3097170 TI - Comparative studies on indirect haemagglutination test and enzyme linked immunosorbent assay for diagnosis of schistosomiasis. PMID- 3097171 TI - Chemical control of some protozoan ectoparasites on young stages of the grass carp, Ctenopharyngodon idella val. PMID- 3097172 TI - Treatment of ascites by continuous ultrafiltration and reinfusion of protein concentrate. PMID- 3097173 TI - Studies on the effect of Amoscanate on the immature stages of S. mansoni and S. haematobium worms in hamsters. PMID- 3097174 TI - Long-term results of augmentation of the atrophic mandible. AB - This is a report on the long term results of Visor-Sandwich Osteotomy. From 1979 until now, more than 60 patients with extreme atrophy of the mandible were operated on. All patients underwent bone transplantation from the iliac crest, and, about half a year later, mouth-floor and vestibuloplasties with skin grafting were done. 29 patients were selected who had been operated on by the same oral surgeon. The purpose of this investigation was: a. to investigate the number of sensitivity disturbances in the mental nerve area; b. to get an impression of the overall results; and c. to determine the rate of resorption of the mandible after osteotomy, bone grafting and vestibuloplasty, which were carried out 1.5 to 5 years previously. PMID- 3097175 TI - Compression osteosynthesis in mandibular fractures. AB - A study of the results of 26 cases of mandibular fracture treated by dynamic compression osteosynthesis by means of compression plates is presented. The advantages and disadvantages and complications of this technique are discussed. PMID- 3097176 TI - Lingua fissurata. A clinical, stereomicroscopic and histopathological study. AB - The purpose of this study was to describe clinical, stereomicroscopic and light microscopic findings for fissured tongue in 17 patients and compare them with 17 normal controls. Clinical symptoms were found in 13 of 17 patients who complained of scoreness of the tongue. Usually the symptoms lasted more than 3 years. In 15 cases, fissures involved the entire tongue, while in 2 cases, only the edges of the tongue were affected. In all patients, papillae of varying sizes were found in the area of fissures. The papillae were easily noted using stereomicroscopy on fixed-tissue specimens, but could also be seen with the naked eye during careful clinical examinations. Light microscopic studies indicated that the number of inflammatory cells was far greater in the mucosa of fissured tongues than in normal tongues, and this inflammation was not confined only to the fissures. The rete pegs of the epithelium were longer in fissured tongues than in normal tongues, 800 (+/- 79) micron and 620 (+/- 69) micron, respectively, (p less than 0.001). The lamina propria was also thicker in fissured tongues than in normal tongues, 390 (+/- 74) micron and 170 (+/- 61) micron, respectively, (p less than 0.001). In normal tongues, keratohyaline granules were observed in the filiform papillae around the area of hairs but these granules were absent in fissured tongues. PMID- 3097177 TI - Aneurysmal bone cyst of the jaws. Review of the literature and report of 2 cases. AB - Strictly speaking, the aneurysmal bone cyst is not a true cyst. It is a lesion characterized by replacement of bone by fibro-osseous tissue containing blood filled cavernous spaces. It is usually treated by surgical curettage, and access within the jaws may sometimes be difficult. We reviewed the world literature and found 63 cases of aneurysmal bone cysts involving the face, 22 reported in the maxilla, and 63 in the mandible. One was found in the zygomatic arch. Of the patients reported, 88% were younger than 30 years old; there was an equal sex distribution. Included in this report, are two cases of our own, one involving the maxilla and one the mandible. PMID- 3097178 TI - Intravenous or rectal diazepam for outpatient sedation in minor oral surgery. AB - In a randomized cross-over study on sedation in outpatient oral surgery, intravenous and rectal administration of diazepam were compared. The mean dose for intravenous diazepam was 0.22 mg X kg-1 (range 0.15-0.38) and for rectal diazepam 0.58 mg X kg-1 (range 0.50-0.71). The determining factors for the patients' preference for sedation method, apprehension, effect produced by the sedative, recovery from sedation and the postoperative course were studied. The patients preferred the session in which they experienced stronger effect, regardless of the route of administration. Patient preference for sedation method did not differ when optimal dose regimens were used, and a preset dose of 10 mg rectal diazepam did not produce the desired effect. Apprehension was significantly higher prior to and during the first operation than the second operation, and all patients recovered from sedation within 2 1/2 hours after the administration. PMID- 3097179 TI - A holistic approach to stylalgia. AB - A follow-up study was performed on 20 patients surgically treated because of stylalgia (Eagle's Syndrome). The aim of the study was to investigate why somatic treatment was often ineffective; furthermore, if there was a psychosomatic background to the complaints. The results of a psychiatric interview in which 11 patients took part clearly showed that most of them were suffering primarily from a psychiatric disorder. The question of stylalgia only as a form of atypical facial pain is discussed. PMID- 3097180 TI - Chondromyxoid fibroma. AB - A brief review of the literature concerning chondromyxoid fibroma is presented. 7 previous cases and the present case of the tumor in the jaws are described. Parallels to the extra oral lesions are drawn and in the light of previously published data, distinctive diagnostic features are discussed. The importance of close cooperation between the surgeon, the radiologist and the pathologist is stressed to avoid a misdiagnosis and radical treatment of the malignant counterpart of a rare benign tumor. PMID- 3097182 TI - The incidence of impacted wisdom teeth in a Saudi community. AB - The wisdom tooth is the last permanent tooth to erupt into the oral cavity. Its eruption, however, can be impeded and the tooth may become impacted. The incidence of such a condition may be influenced by local as well as racial factors. In this article, an attempt was made to establish the incidence of impacted wisdom teeth in a small sample of the Saudi population. PMID- 3097181 TI - Incidence of cleft lip and cleft palate in 39,696 Japanese babies born during 1983. AB - To estimate the incidence of cleft lip and/or cleft palate among the Japanese, 39,696 Japanese babies born during the period from January 1, 1983 to December 31, 1983, were investigated. It was found that 65 babies (0.163%) had these abnormalities, and that the ratio of the birth of such babies was approximately one per 611 in the population. Of the 65 affected babies, 41.3% presented cleft lip (CL), 46.0% cleft lip and palate (CL/P), and 12.7% cleft palate (CP). These results suggest that the incidence of CL/P in the Japanese is higher than that observed among other races. PMID- 3097183 TI - Nasopalatine duct cyst. AB - A retrospective and follow-up study of 35 cases of nasopalatine cysts was performed. The retrospective part of the investigation comprised clinical, radiological and histological observations including pre-, intra- and post operative findings. The follow-up included clinical and radiological observations. The results indicated that most cysts are found during routine clinical and radiological examination. Subjective and objective clinical symptoms were reported in 50% and 59% of the cases, respectively, the most common being swelling and pain. It was not possible to confirm any specific etiological factor. In 97% of the cases, maximum cyst diameter varied between 1.0-2.5 cm and 84% appeared round or ovoid. Histological examination revealed a high frequency of cuboidal and/or columnar epithelial lining, 2-3 cell layers thick, in combination with an adjacent zone of hyalinized capsular tissue with low-grade inflammation. Radiologically these cases exhibited a well-defined cortical border. In the follow-up study, 84% of the patients exhibited complete clinical healing with no objective or subjective symptoms. Complete bone regeneration was seen radiologically within 3 years in 82% of the cases examined. The results of the present study were compared to those obtained in previous reports. PMID- 3097184 TI - Pedicled "flap" from a tongue flap. AB - A pedicled musculo-mucocutaneous "flap" derived from an original tongue flap is used as one of the layers for the double-layered closure of a recurring oro-nasal fistula. The other layer used for the closure, namely the nasal "flap" layer, originates from the adjacent palatal mucoperiosteum. The oral pedicled "flap" layer and the nasal "flap" layer form the final double-layered flap. This technique gives satisfactory closure of the persistent oro-nasal fistula. PMID- 3097185 TI - A novel and non-invasive method for the removal of salivary gland stones. AB - A non-invasive method for salivary gland stone disintegration by shock waves is proposed. An in vitro experiment, in which a large sialolith was subjected to shock waves produced by a Dornier lithotriptor, demonstrated the complete destruction of the stone. The advantages of the method and the need for modification of the existing equipment is discussed. PMID- 3097186 TI - The Shaw Scalpel: thermal control of surgical bleeding. AB - Hemostasis during surgical procedures has always been a primary concern in patient treatment. The Shaw Scalpel represents a significant development in the surgeon's armementarium to control hemorrhage in soft tissue surgery. It offers immediate hemostasis, improved visibility, and reduced blood loss. Surgery can be performed using a single instrument for simultaneous cutting and sealing of vessels without passing any electrical current through the patient's body. Tissue healing rates are similar to cold steel and significantly better than with electrosurgical techniques. PMID- 3097187 TI - Computer-aided diagnosis of odontogenic lesions. AB - 4 cysts and 8 tumors of odontogenic origin have been described for the computer in terms of the prevalence of the associated clinical and radiological findings. Symptom prevalence as given in the literature and modified by our own experience was stated quantitatively as incidence ratios so that Bayes' formula could be used to calculate the probability of each disorder for each set of patient data. The model was applied to 48 cases whose lesions were identified by histopathology following surgery. In all cases, the actual lesion was listed in the computer produced differential diagnosis, in 94% of the cases the lesion headed the list, and in 75% a probability of 0.85 or greater was achieved. The model can thus be applied to patients awaiting surgery to obtain a reliable differential diagnosis for guiding the medical staff in the proper management of the patient. PMID- 3097188 TI - Inflammatory cells and bacteria in pericoronal exudates from acute pericoronitis. AB - The present work is one in a series of studies carried out to verify the relationship between bacteria and gingival tissues in pericoronitis. Exudates from 6 cases of acute pericoronitis were examined by light and electron microscopy, including ultrathin sections and negative staining. While bacterial phagocytosis was prevalent in all the exudates studied, spirochetes, which were the predominant microorganisms, were not observed being phagocytized by PMNs or macrophages. The presence of spirochetes in pericoronitis as compared with acute necrotizing ulcerative gingivitis is discussed. PMID- 3097189 TI - Intralesional T lymphocyte phenotypes and HLA-DR expression in Melkersson Rosenthal syndrome. AB - An immunohistochemical double-staining technique was used to characterize the infiltrating mononuclear lymphocytes in frozen sections from 3 patients with Melkersson-Rosenthal syndrome. The in situ expression of HLA-DR antigens on different cell types was also investigated. The majority of mononuclear cells could be classified as T-lymphocytes because of their Leu 4 antigen expression. Most of the T-lymphocytes were confined to the helper/inducer lymphocyte subset since they reacted with Leu 3a antibodies. However, big infiltrates of suppressor/cytotoxic lymphocytes with the Leu 2a phenotype were noted in some specimens. These cells were situated between the ducts of the salivary glands. Virtually all mononuclear infiltrating cells carried HLA-DR antigens. HLA-DR expressing keratinocytes were found in the biopsy from one patient. The present study indicates that a local immune response may be important in the pathogenesis of the oro-facial lesions in Melkersson-Rosenthal syndrome. PMID- 3097190 TI - Experimental mandibular Staphylococcus aureus osteomyelitis; antibody response and treatment with dicloxacillin. AB - Staphylococcus aureus mandibular osteomyelitis was produced in 20 rabbits by injection of a sclerosing agent and 1 X 10(9) colony-forming units of Staphylococcus aureus V8 into the medullary cavity of the mandible. After 2 weeks all rabbits developed infections. 10 of the rabbits were then treated with dicloxacillin (22.5 mg/kg body weight) every 12 h for 7 days and 10 were left untreated. The animals were sacrificed after 8 weeks and histopathological examination was performed. An enzyme-linked immunosorbent assay (ELISA) was used to measure IgG response against staphylococcal teichoic acid and alpha-toxin during the observation period. In the treated group, there was a decrease in clinical symptoms after the treatment period, while in the untreated group, progression of the infection was a common finding. At the end of the treatment period, Staphylococcus aureus V8 could not be recovered from aspirates obtained from animals in the treatment group, while in the non-treatment group, Staphylococcus aureus V8 could be recovered from abscesses in 6 rabbits. Both in the treated group and in the untreated group, the rabbits showed increasing IgG titers against teichoic acid and alpha-toxin during the first 2-3 weeks. No significant differences in antibody response patterns were noted between the treated and untreated groups and no clear correlation between the immunological response and the severity of the disease was observed. PMID- 3097191 TI - Partial glossectomy for macroglossia in an elderly acromegalic. A case report. AB - A case is presented where the enlargement of the tongue due to acromegaly failed to respond to bromocriptine therapy, resulting in marked dysarthria. A partial glossectomy technique for tongue reduction is described, and the surgical and anaesthetic problems associated with acromegaly are discussed. PMID- 3097192 TI - Adenomatoid odontogenic tumor mimicking a globulo-maxillary cyst. AB - A case of an adenomatoid odontogenic tumor (AOT) simulating a globulo-maxillary cyst is described. Clinical, radiographic and microscopic findings as well as the differential diagnosis are discussed. The present case brings the number of AOT cases without any relationship to an impacted tooth to 23; the number of cases resembling a globulo-maxillary cyst to 6. PMID- 3097193 TI - Calcifying odontogenic cyst. AB - The literature pertinent to calcifying odontogenic cysts is reviewed, and an additional case is described. Relevant clinical, radiological and histological features, as well as methods of treatment are considered, and an unusual method of treatment with good results is described in detail. PMID- 3097194 TI - Malignant melanoma of a parotid lymph gland. An unusual case. AB - A case of malignant melanoma in an intra-parotid lymph gland treated by excision is reported. The patient remains disease-free 9 years after surgical treatment, and no primary lesion has been found. PMID- 3097195 TI - Thyroid papillary carcinoma presenting as jaw and parotid gland metastases. AB - A slowly progressing colloidal goiter of 20 years standing was excised in a 67 year old woman. Two years later, a metastatic tumor inducing facial swelling was diagnosed radiologically in the left parotid gland and left ascending mandibular ramus. The incisional biopsy confirmed papillary carcinoma of thyroid origin. The patient refused treatment. Six months later, she returned to the clinic and presented with advanced destructive changes of the involved structures. This rare case of unrestricted malignant growth may shed light upon the sequence and mode of metastatic invasion. PMID- 3097196 TI - [The effect of cefixime (CFIX) on intestinal bacterial flora]. PMID- 3097197 TI - [Prevalence of Campylobacter jejuni complement fixing antibody in healthy people]. PMID- 3097198 TI - [M. genitalium; studies on biological characteristics and pathogenicity in the experimental animal respiratory tract]. PMID- 3097199 TI - [Trends in childhood bacterial meningitis in Japan (1979-1984). (Part 1). On the causative organisms]. PMID- 3097200 TI - [Staphylococcal bacteremia. 2. Review of 93 cases with Staphylococcus aureus bacteremia of the aged]. PMID- 3097201 TI - [Intestinal microflora of patients with antibiotic-associated hemorrhagic colitis associated with Klebsiella oxytoca and Clostridium difficile enterotoxin]. PMID- 3097203 TI - [A case of Salmonella prostatitis in a renal transplant patient]. PMID- 3097202 TI - [Pharmacological study of Candida polysaccharide on the cardiovascular system of non-immunized and immunized rats]. PMID- 3097204 TI - [A case of septicemia caused by Alcaligenes dentrificans subspecies xylosoxidans and a review of the literature]. PMID- 3097206 TI - [Experimental urinary tract infection in mice to evaluate the pathogenicity of Escherichia coli]. PMID- 3097205 TI - [Long-term observation on the immunogenicity of hepatitis B vaccine in infants and adults]. PMID- 3097208 TI - [Bile acid composition and bacteria in biliary tract infections]. PMID- 3097207 TI - [A foodborne outbreak of streptococcal sore throat occurring in Tokyo, 1983]. PMID- 3097209 TI - [A saved case of Vibrio vulnificus infection with shock, DIC and necrotizing fasciitis]. PMID- 3097210 TI - [A case of Mycoplasma pneumonia, complicated by autoimmune cold agglutinin hemolytic anemia]. PMID- 3097211 TI - [Black water fever associated with quinine-MP therapy of a malaria patient]. PMID- 3097212 TI - [Sternocostoclavicular hyperostosis: a report of nineteen cases with special reference to its etiology and treatment]. AB - Nineteen patients with sternocostoclavicular hyperostosis were reviewed retrospectively. Of particular interest were their responses to antibiotics and prostaglandin inhibitors. The prostaglandin inhibitors relieved the pain within four weeks in 16 of 18 patients. In most cases, however, the inhibitors gradually became less effective. Oral antibiotics were more effective than the inhibitors in relieving the pain in 8 of 10 patients who were given antibiotics. Pustulosis palmaris et plantaris, commonly associated with sternocostoclavicular hyperostosis, diminished after antibiotic therapy as did the chest pain in most cases. The similarities between age and sex distribution, and the responses to antibiotics of the patients with sternocostoclavicular hyperostosis and those with pustulosis suggest that these disorders have a common etiology, and that the pustulosis may represent "bacterid reaction", and the hyperostosis may also be a manifestation of a systemic reaction to a focal infection. PMID- 3097213 TI - [Clinical study of combination chemotherapy with cisplatin (CDDP), continuously infused 5-fluorouracil (5-Fu) and mitomycin C (MMC) (PFM therapy)]. PMID- 3097214 TI - [Experimental study of esophageal cancer--effect of alcohol, vitamin C, prostaglandin E2 and tegafur on carcinogenesis by N-methyl-N-amylnitrosamine and the development of esophageal carcinoma]. PMID- 3097215 TI - [A study on the application of combined treatment of Nd-YAG laser irradiation and radiotherapy in unresectable advanced lung cancer]. PMID- 3097216 TI - [Primary macroglobulinemia associated with bone destruction]. PMID- 3097217 TI - [An autopsy case of IgD-myeloma with an initial clinical manifestation of nephrotic syndrome]. PMID- 3097218 TI - [Two cases of women with Fabry's disease detected by electrocardiographic abnormalities]. PMID- 3097219 TI - Growth of mouse embryos in bicarbonate media buffered by carbon dioxide, hepes, or phosphate. AB - The purpose of this study was to determine if mouse embryos could be grown successfully in a culture medium devoid of the carbon dioxide phase (CO2). Mouse embryos fertilized in vivo were collected and cultured in Hepes medium with and without bicarbonate (HCO3-) and a phosphate medium with and without HCO3-. In these experiments no CO2 gas phase was used. Further embryos were cultured in Whittingham's modified Tyrode's (T6) medium with a CO2 gas phase and served as controls. The degree of embryonic development was noted. Surviving blastocysts were transferred to the uteri of pseudopregnant mice and delivery at term was allowed to occur. There was no significant difference in the degree of embryonic development in those embryos cultured in T6 or Hepes medium (+ HCO3-) or in the number of live offspring obtained when these blastocysts were placed within the mouse uterus. Although embryonic development apparently proceeded successfully in the phosphate (+ HCO3-) medium, none of these blastocysts survived when transferred to mouse uteri. No embryonic growth occurred in either the Hepes or phosphate media which were devoid of HCO3-. It appears that a Hepes medium containing HCO3-, which uses no CO2 gas phase, is as effective as T6 medium, which uses a gas phase, in supporting in vitro mouse embryonic growth. PMID- 3097220 TI - Superovulation of mice with human menopausal gonadotropin or pure follicle stimulating hormone in combination with human chorionic gonadotropin and the effects of oocyte aging on in vitro fertilization. AB - The response of female mice of F1 hybrids (CBA x C57/BL) to superovulatory doses of human menopausal gonadotropin (hMG) or pure follicle-stimulating hormone (FSH) in combination with human chorionic gonadotropin (hCG) was studied. Furthermore, the effect of oocyte aging in vivo on the subsequent rate of fertilization in vitro was also investigated. The oocytes were collected at 12, 18, and 24 hr after hCG injection and in vitro fertilization (IVF) was carried out in T6 medium. A higher proportion of animals responded to hMG stimulation (32/70) compared to pure FSH (15/66). Furthermore, hMG gave a higher oocyte recovery (454/32) than pure FSH (77/15). Fertilization rates of 57.8, 51.5, and 53.5% were obtained for the 12-, 18-, and 24-hr groups, respectively, after correction for parthenogenetic division of oocytes in the controls. No significant differences in fertilization rates were observed among the three time intervals used in recovering oocytes. However, as the degeneration and parthenogenetic division increased with the delay in collection of oocytes, 12 hr post-hCG injection was the best time to collect oocytes to obtain optimum results in in vitro fertilization. PMID- 3097221 TI - The assessment of gas exchange by automated analysis of O2 and CO2 alveolar to arterial differences. AB - A computer program to measure breath by breath alveolar pressure (PA) and alveolar to arterial difference (AaD) for O2 and CO2, by a mass-spectrometer has been implemented. The program allows the determination of alveolar gas by different methods: 1. Bohr's equation (BE); 2. ideal alveolar air equation for O2 (IDO2); 3. end-tidal (ET); 4. by the Rahn's definition of 'mean alveolar gas', i.e., alveolar pressures are defined when instantaneous respiratory exchange ratio (IRQ) equals mean respiratory exchange ratio (MRQ). This automated technique has been used in 16 patients with chronic obstructive lung disease (COLD) and 15 patients with pulmonary embolism (APE). In both groups of patients it was always possible to find in each breath the point where IRQ = MRQ and therefore to measure AaD by RD. IDO2 was significantly lower than PAO2 by the other methods. Also ET values of O2 and CO2 were significantly different from RD and BE in both groups of patients, however the difference was consistently higher in COLD patients. The different shape of the expirograms (steeper expirograms in COLD) is responsible for this different result. RD and BE AaD characterize gas exchange more precisely than ET, because the contribution of high VA/Q units is also evaluated. This is particularly important in COLD patients. Consideration on dead space measurements are also reported both for COLD and APE patients. In conclusion this automated technique provides the assessment of gas exchange for the use in clinical respiratory physiology and for the monitoring of gas-exchange in critically ill patients. PMID- 3097222 TI - In vitro formation of activators for prostaglandin synthesis by neutrophils and macrophages from humans and guinea pigs. AB - Prostaglandin H synthase, the primary enzyme in the pathway to the prostaglandins, requires the continued presence of a hydroperoxide activator for its enzyme activity. Phagocytic leukocytes from either humans or guinea pigs produced activator hydroperoxides in quantities sufficient to enhance prostaglandin synthesis in cells. Compounds that stimulated the oxidative burst (e.g., phorbol myristate acetate, opsonized zymosan, and N-formyl-L-methionyl-L leucyl-L-phenylalanine) enhanced the overall production of the activators. Accumulation of activator(s) was promoted by exogenous Fe+3 (2 mumol/L), adenosine diphosphate (10 mumol/L), and unsaturated fatty acids (1 to 30 mumol/L) and was completely inhibited by glutathione peroxidase (0.5 U/ml). Catalase (500 U/ml) decreased the amount of activator by 70% when added during the incubation but by only 40% when added after the incubation. Thus, the activator appeared to be partly H2O2 and partly a lipid hydroperoxide. The addition of H2O2 in quantities similar to those produced by phagocytes increased prostaglandin formation by twofold in incubations with U937 cells and carbon 14-labeled arachidonic acid (2 mumol/L). These results indicate a new role for the oxygen metabolites from leukocytes in providing an intercellular signal that can stimulate prostaglandin synthesis. PMID- 3097223 TI - Low-dose enteric-coated aspirin: a practical approach to continuous-release low dose aspirin and presystemic acetylation of human platelet cyclooxygenase. AB - Using a granular enteric-coated aspirin (ECA) preparation, we achieved continuous release of low-dose aspirin and associated inhibition of platelet reactivity. The lowest once-daily dose that produced greater than 90% inhibition of serum thromboxane (TX) A2 after 7 days was 80 mg. The time course of inhibition after the first dose indicated a gradual release of aspirin over a period of 8 hours. We subsequently fractionated this 80 mg dose into three times daily doses of 27 mg that were administered to nine healthy men for 7 days. This regimen resulted in 96% inhibition of serum TXA2 generation (P less than 0.001), inhibition of in vitro platelet aggregation (P less than 0.05), prolongation of the bleeding time by 75% (P less than 0.01), and a threefold increase in inhibition of platelet aggregation by prostacyclin (P less than 0.01) compared with pre-ECA values. In contrast to our previous study using daily 80 mg doses of ECA, after the 27 mg three times daily regimen we found a significant increase in circulating platelet cyclooxygenase activity 24 hours after the final dose (P less than 0.05). This immediate recovery indicates active megakaryocyte cyclooxygenase and suggests that acetylation of platelet cyclooxygenase was restricted to the presystemic circulation. We conclude that long-term dosing with 27 mg ECA three times daily results in profound inhibition of platelet TXA2 production, and diminished in vitro and in vivo platelet reactivity. This regimen provides a practical approach to achieving continuous release of low-dose aspirin and possible presystemic acetylation of platelet cyclooxygenase. PMID- 3097224 TI - Biochemical analysis and biological activities of immunoaffinity purified natural murine gamma interferon (MuIFN-gamma). AB - A rapid one-step procedure for the purification of natural murine gamma interferon (MuIFN-gamma) by immunoaffinity chromatography has been developed. Crude MuIFN-gamma was passed through a column containing immobilized anti-MuIFN gamma monoclonal antibody, and the column was washed with high salt and detergent. Active MuIFN-gamma was subsequently eluted with ammonium thiocyanate/glycerol (yields of 20-40%). Analysis of the immunopurified interferon by sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions revealed biologically active bands of about 19.5, and 14 kd. Under nonreducing conditions, three active bands at 35, 19.5, and 14 kd could be seen. Gel filtration of the immunopurified MuIFN-gamma under reducing or nonreducing conditions showed a single major peak of antiviral activity corresponding to a molecular weight of 43 kd. The protein eluted from each band from the SDS-gel, in addition to possessing antiviral activity, was shown to activate macrophages in three assays: macrophage tumoricidal activity, hydrogen peroxide secretion, and expression of la antigen on the surface of exudate macrophages. PMID- 3097225 TI - Comparison of five short-term assays that measure nonspecific cytotoxicity mediated to tumor cells by activated macrophages. AB - Five different short term assays (less than 48 h) used to measure macrophage mediated, nonspecific cytotoxicity were compared under similar conditions in the same laboratory using the same reagents. The purpose was to determine the extent to which results were comparable. Three of the assays were dependent on the release of a radioisotope to measure cytotoxicity, one was dependent on cell counting, and the last was dependent on flow cytometric quantification of remaining viable tumor target cells after they had been exposed to macrophages. The variables examined were the following: three different populations of macrophages; four different kinds of target cells; two types of radioisotopes; and two different agents that trigger the expression of cytolytic activity by primed macrophages. Recombinant gamma interferon was used as the priming agent in all the experiments. There was unexpectedly good agreement between the results of the various assays. No differences were found among the different macrophage populations, the isotopes or the triggering agents. Perhaps the most important finding was that differences in target cell susceptibility to killing by activated macrophages, which were apparent in assays of less than 24 h duration, disappeared when the same kinds of targets were compared in assays of greater than 40 h duration. The results of this study are an important first step toward standardizing the way in which macrophage-mediated, nonspecific cytotoxicity is measured in short-term assays, laboratory to laboratory. PMID- 3097226 TI - Arachidonic acid mobilization among phospholipids in murine mastocytoma P-815 cells: role of ether-linked phospholipids. AB - The ethanolamine-containing glycerophospholipids, choline-containing glycerophospholipids, and phosphatidylinositol fractions are major sources of arachidonic acid in murine mastocytoma P-815 cloned cells. The choline-linked fraction contained high arachidonic acid contents in 1-O-alkyl-2-acyl- (18%) and 1,2-diacyl-sn-glycero-3-phosphocholine (11%), with smaller amounts in 1-O-alk-1' enyl-2-acyl species, whereas the arachidonic acid content of the ethanolamine linked fraction was high in 1-O-alk-1'-enyl-2-acyl (26%) and 1,2-diacyl species (15%) and low in 1-O-alkyl-2-acyl species. The uptake and transfer of [3H]arachidonic acid into the 1,2-diacyl and ether classes of choline-containing glycerophospholipids and ethanolamine-containing glycerophospholipids in mastocytoma cells were examined. There was very rapid incorporation of radioactive arachidonic acid into mastocytoma cells that leveled off after 30 min. By labeling cells with [3H]arachidonic acid for 7.5 min, the radioactivity was recovered in the choline-containing glycerophospholipids (43%), phosphatidylinositol (32%), and ethanolamine-containing glycerophospholipids (20%) with little in other phospholipids, neutral lipid, or free fatty acid fractions. Upon reincubation of the mastocytoma cells in the radiolabel-free medium, the [3H]arachidonate radioactivity was gradually lost from the choline containing glycerophospholipids fraction and, concomitantly, increased in ethanolamine-containing glycerophospholipids. At the zero time of reincubation, most of the radioactivity was recovered in the 1,2-diacyl species of both choline containing glycerophospholipids and ethanolamine-containing glycerophospholipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097227 TI - Metabolism of essential fatty acids by human epidermal enzyme preparations: evidence of chain elongation. AB - The present studies were undertaken in order to delineate the source of human epidermal arachidonic acid, 20:4(n-6). Epidermal microsomal preparations from normal (N) and diseased epidermis (clinically uninvolved (PU) and involved psoriatic (PI) epidermis) were incubated in vitro with either [14C]18:2(n-6), [14C]20:3(n-6) or [14C]malonyl CoA to determine the activities of the delta 6, delta 5 desaturases and elongate, respectively. Experiments were performed in parallel with rat liver microsomal preparations where enzyme activities are well documented. Data derived from the enzymatic assays were compared to fatty acid composition data derived from epidermal total lipids. The enzymatic conversion rates were determined after methylation and separation of the 14C-labeled fatty acid methyl esters by argentation thin-layer chromatography and reverse phase high-performance liquid chromatography. Our data demonstrated: that N, PU, and PI epidermis were all capable of elongating 18:3(n-6) into 14C-labeled 20:3(n-6) via the addition of [14C]malonyl CoA, and this activity was markedly elevated (fivefold) in PI preparations; that N, PU, and PI epidermal preparations lacked the capacity to desaturate 18:2(n-6) and 20:3(n-6); and striking alterations in the individual fatty acids (as weight percent) in the total fatty acids of the PI epidermal extracts when compared to the PU and N extracts. These findings indicate that epidermal arachidonic acid is not biosynthesized locally from tissue linoleic acid and must, therefore, depend on contribution from another endogenous source. PMID- 3097228 TI - Nascent high density lipoproteins from liver perfusates of orotic acid-fed rats. AB - Uniformly fatty livers from orotic acid-fed rats secreted almost no very low density lipoproteins (VLDL) but normal amounts of nascent high density lipoproteins (HDL) accumulated in perfusates. When lecithin:cholesterol acyltransferase (LCAT) was inhibited, nascent HDL were uniformly discoidal and lacked cholesteryl esters. Lipid and apoprotein compositions of nascent HDL from normal and fatty livers were similar whether LCAT was inhibited or not. Apolipoprotein B-100 was not detected in perfusates of uniformly fatty livers, but small amounts of apolipoprotein B-48 were present in HDL2 fractions. Nascent lipoproteins were not seen in Golgi compartments, but lipid-rich particles were clearly evident in endoplasmic reticulum cisternae adjacent to the cis face of the Golgi complex, suggesting that orotic acid blocks VLDL secretion by preventing translocation of nascent particles from the endoplasmic reticulum to the cis Golgi compartment. The accumulation of normal amounts of discoidal HDL in liver perfusates despite virtual absence of triglyceride-rich lipoproteins in Golgi secretory compartments, the space of Disse, and the perfusate is inconsistent with the concept that nascent HDL are exclusively a product of surface remnants cast off during lipolysis of chylomicrons and VLDL. PMID- 3097229 TI - Blood-pleural fluid glucose and pleural fluid pH, pCO2 relationship. A report of 80 cases of heterogeneous population with the study after intravenous glucose. PMID- 3097230 TI - Demonstration of thyrotrophin beta-subunit messenger RNA in rat pituitary cells in primary culture--evidence for regulation by thyrotrophin-releasing hormone and forskolin. AB - We have reported previously the effect of thyroid status in vivo on pituitary cytoplasmic concentrations of messenger RNA (mRNA) encoding the thyrotrophin (TSH) beta-subunit (Franklyn, Lynam, Docherty et al, 1985). Studies in vitro of the regulation of TSH beta gene transcription have been confined to thyrotrophic tumour cells. We now report the demonstration of TSH beta-subunit mRNA in non tumorous rat pituitary cells in primary culture. Treatment of cells with thyrotrophin-releasing hormone (TRH) and with forskolin resulted in a marked increase in cellular concentration of TSH beta-mRNA. These results suggest that TRH exerts a direct effect on the pretranslational events involved in TSH synthesis and further that the adenylate cyclase system may be involved in the regulation of synthesis. We have thus described a novel system for the study of TSH beta-subunit gene expression in normal rat pituitary cells in vitro. PMID- 3097231 TI - Suppression of ovine plasma FSH by bovine follicular fluid: neutralization by plasma from ewes immunized against an inhibin-enriched preparation from bovine follicular fluid. AB - Adult Merino ewes were immunized against an inhibin-enriched preparation (bFFI) obtained by affinity chromatography of bovine follicular fluid (bFF). Plasma was obtained in early luteal phase from these ewes and from control ewes immunized against bovine serum albumin. Ten months after ovariectomy the plasma concentration of FSH, but not LH, in control ewes was decreased by four s.c. injections of 8 ml bFFI (17,500 units inhibin/injection). There was no decrease in plasma concentrations of FSH or LH in immunized ewes with the same dose of bFFI. In a second study with long-term ovariectomized ewes, four injections of 20 ml plasma from the immunized ewes significantly reduced the decrease in FSH concentration caused by four injections of steroid-free bFF (2500 units inhibin/injection) in comparison with similar ewes injected with plasma from control ewes. These results show that the plasma of ewes immunized against bFFI contains substances, presumably antibodies, which neutralize the FSH-suppressive effects of bFF and bFFI in ovariectomized ewes. PMID- 3097232 TI - Inhibin increases in the ovaries of female rats approaching first ovulation: relationships with follicle growth and serum FSH concentrations. AB - In order to relate various prepubertal events in a group of 95 late prepubertal female rats, the following data were obtained during the last 10 days before the day of first ovulation: amounts of ovarian inhibin-like activity (ILA) in some animals (n = 47); size and numbers of healthy (antral) follicles with a volume greater than or equal to 100 X 10(5) microns3 (or diameter greater than or equal to 260 microns) present per ovary in their litter-mates (n = 48); serum FSH concentrations in both groups. Rats were unilaterally ovariectomized to obtain an ovary for either estimation of ILA content or for histological procedures and counting of follicles. At the time of unilateral ovariectomy they were bled to obtain serum for estimation of FSH concentrations. Rats were kept until the day after the day of first ovulation to determine the time-interval between the day of unilateral ovariectomy and first ovulation. They were studied between 10 and 1 days (days -10 to -1, maturational age) before first ovulation. In addition, adult cyclic rats were bilaterally ovariectomized on different days of the oestrous cycle for estimation of ovarian ILA content. The amount of ovarian ILA was estimated in steroid-free ovarian cytosols using an in-vitro bioassay system with dispersed anterior pituitary cells and subsequent measurement of FSH and LH in the spent medium. The amount of ovarian ILA was about 83 units/ovary from days -10 to -5, and subsequently increased (P less than 0.005) to reach a maximum on day -1, the day of pro-oestrus (213 units/ovary).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097233 TI - Induction of ovulation during anoestrus in two breeds of sheep with multiple injections of LH alone or in combination with FSH. AB - The gonadotrophic requirements for the induction of ovulation and formation of a viable corpus luteum in two breeds of seasonally anoestrous sheep of differing fecundity was investigated. Welsh Mountain (n = 20) and Damline ewes (n = 19) were given LH or FSH either alone or in combination. Luteinizing hormone was injected i.v. at an increasing frequency for 72 h (one injection every 3 h for 24 h, one every 2 h for 24 h, and one every hour for 24 h) and FSH was injected in an identical manner for the first 36 h of treatment. Exogenous LH alone and in combination with FSH induced a preovulatory LH surge in all 19 ewes and ovulation in 18 out of 19 ewes of both breeds. However exogenous FSH alone was ineffective. The incidence of normal corpus luteum function in ewes induced to ovulate was low and not related to treatment, timing or magnitude of the LH/FSH surge. It is concluded that in both breeds studied it is the infrequency of LH pulses which limits the development of preovulatory follicles during seasonal anoestrus, that the requirement for FSH remains unknown, and that the induction of inadequate corpora lutea during seasonal anoestrus reflects either defects in hormonal priming of the preovulatory follicle and/or inappropriate luteotrophic support after ovulation. PMID- 3097234 TI - Effects of constant infusion of gonadotrophin-releasing hormone in ovariectomized ewes with hypothalamo-pituitary disconnection: further evidence for differential control of LH and FSH secretion and the lack of a priming effect. AB - Experiments were conducted in ovariectomized ewes after hypothalamo-pituitary disconnection (HPD) to examine LH and FSH secretion during constant infusion of gonadotrophin-releasing hormone (GnRH) or physiological saline and to determine whether or not a constant GnRH background enhances or diminishes pituitary responsiveness to GnRH pulses. Whereas pulsatile GnRH infusions maintained LH and FSH secretion, constant infusions (125 or 250 ng/h) led to the complete cessation of LH secretion and reduced FSH secretion. The rate of decline of plasma FSH concentrations was significantly (P less than 0.01) greater in animals receiving 250 ng GnRH/h than in saline-treated animals, whereas that in animals receiving 125 ng/h was not significantly different. When GnRH pulses were administered during constant GnRH infusion, the plasma LH pulse amplitudes were similar to those seen without the GnRH background. These data show that, in ovariectomized HPD ewes FSH secretion does not require GnRH pulses and may merely reflect ongoing FSH synthesis and a constant low background of GnRH does not affect pituitary responsiveness to GnRH pulses. PMID- 3097235 TI - Evidence of gonadal steroid-independent changes in activity of the central LH releasing hormone pulse generator in developing bull calves. AB - To ascertain whether temporal changes in activity of the hypothalamo-pituitary axis in prepubertal bulls may occur independently of shifts in sensitivity to steroid feedback, the acute post-castration rise in serum gonadotrophins was monitored in bull calves castrated at monthly intervals from 4 to 9 months of age. Since a major feature of the gonadotrophin profiles of developing bulls is a change in LH pulse frequency early in life, pulsatile LH secretion after castration was used as an index of activity of the central LH-releasing hormone (LHRH) pulse generator. Relative to the day of castration (day 0) bull calves (n = 4) were bled at 20-min intervals for 8 h on day -3 and at 10-min intervals for 4 h on days 3, 5 and 7. During the first week after castration, 4-month-old bulls showed a higher (P less than 0.05) frequency of LH pulses compared with bulls at 8 and 9 months (1.13, 0.88 and 0.75 pulses/h respectively; pooled S.E.M. = 0.13). Mean LH levels before castration were higher (P less than 0.05) in 4-month-old bulls than in bulls at 7, 8 and 9 months (0.92, 0.37, 0.31, 0.38 micrograms/l respectively; pooled S.E.M. = 0.12). After castration mean LH levels did not differ with age. Mean FSH levels did not differ among age groups either before or after castration. Increased serum LH levels in 4-month-old bulls confirmed the transient rise in LH secretion that occurs at this time in developing bull calves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097236 TI - Effects of an LH-releasing hormone antagonist on the secretion of LH, FSH, prolactin and ovarian steroids at different stages of the luteal phase in the stumptailed macaque (Macaca arctoides). AB - The role of the pituitary gonadotrophins in controlling luteal function in the stumptailed macaque has been investigated by examining profiles of serum concentrations of LH, FSH, progesterone and oestradiol in daily blood samples from 13 monkeys during the menstrual cycle, and in blood samples taken at hourly intervals between 09.00 and 21.00 h on different days of the luteal phase in 13 cycles. The effects of acute withdrawal of gonadotrophins was investigated by administering a single injection of 300 micrograms LHRH antagonist/kg body weight at different stages of the luteal phase during 28 cycles. Although there were high basal values and marked fluctuations of bioactive LH during the first 4 days after the LH peak, progesterone profiles showed no corresponding short-term changes, there being a slow and steady rise in progesterone concentrations during the sampling periods. After day 5, basal LH secretion decreased, but high amplitude LH pulses were identified which were associated with episodes of progesterone secretion. Administration of the LHRH antagonist caused a suppression of bioactive LH and progesterone concentrations at all stages of the luteal phase, although some basal secretion of progesterone was maintained through the 24-h period of effective antagonist gonadotroph blockade. Luteal function recovered apparently normally in all monkeys treated in the early-mid luteal phase. Serum concentrations of FSH and oestradiol fluctuated comparatively less during the 12-h sampling periods, and the antagonist had less suppressive effects on the concentrations of these hormones. The LHRH antagonist had no apparent effect on prolactin release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097237 TI - The Ro/SSA autoantigen as an immunogen. Some anti-Ro/SSA antibody binds IgG. AB - The rheumatic disease autoantigen, Ro/SSA, was immunogenic to a rabbit host. The heteroimmune rabbit serum bound the Ro/SSA particle in immunoblots and in an ELISA. Both the rabbit anti-Ro/SSA and a human prototype anti-Ro/SSA serum also bound IgG; and moreover, IgG inhibited both rabbit and human anti-Ro/SSA activity. Anti-IgG activity of the rabbit and human anti-Ro/SSA sera bound Ro/SSA by Western blot and solid-phase assays. In addition, purified Ro/SSA inhibited the anti-IgG activity of the anti-Ro/SSA sera from rabbit and man. Affinity purification of the IgG- and Ro/SSA-binding fractions of the rabbit anti-Ro/SSA demonstrated that both the anti-Ro/SSA and anti-IgG activities were concentrated in these fractions. These data show that Ro/SSA and IgG share epitopes that are bound by anti-Ro/SSA antibody. Inhibition experiments suggest that this antibody is found in most human anti-Ro/SSA autoimmune sera and that the epitope(s) are found in the F(ab')2 fragment of IgG. PMID- 3097238 TI - Isolation and preliminary biochemical characterization of the gonococcal H.8 antigen. AB - We have presented a method for the extraction and isolation of the gonococcal H.8 antigen. There was no evidence of contamination by other gonococcal proteins, phospholipids, or LPS. The purified H.8 antigen was subjected to preliminary analysis and appeared to be a proteolipid consisting of both protein and lipid components. The amino acid composition was unusual; the peptide portion of the antigen was an alanine and proline-rich molecule that lacked aromatic and sulfur containing amino acids. The overall amino acid composition is hydrophobic. A lipid constituent was also identified; it was made up of at least two lipid components, which were unique to the H.8 molecule. The chemical nature of the association of the protein and lipid is presently unknown, but it is clearly a tenacious one. PMID- 3097241 TI - Neopterin and interferon gamma serum levels in patients with heart and kidney transplants. AB - The main problem in the follow-up of patients receiving organ allografts is the early differential diagnosis of rejection episodes and infections. Serum levels of interferon gamma, a marker of T-lymphocyte activity, were determined with an immunoradiometric assay, specific for biologically active interferon gamma and sufficiently sensitive (20 U/l) for the determination of circulating interferon gamma. Neopterin, a pteridine released from stimulated macrophages, was determined by radioimmunoassay. Both rejection crises and infections are accompanied by distinct increases of serum neopterin (median values 124 and 128 nmol/l; N = 98). Interferon gamma levels are elevated for a short period one or two days earlier, the maximal values during infections (median 430 U/l, range 120 1220 U/l, N = 25) being higher than those during rejection episodes (median 120 U/l, range less than 20-330 U/l, N = 73). Each rise of interferon gamma was followed by an increase of neopterin, but not every neopterin increase was preceded by a interferon gamma peak. Neither of these parameters showed an increase during deterioration of kidney function due to cyclosporin toxicity. The determination of interferon gamma, a lymphokine involved in the activation of alloreactivity, reflecting T-cell stimulation, and the measurement of neopterin, a secretory product of activated macrophages, allows the simple, quick and reliable monitoring of the immune status of transplant recipients. PMID- 3097239 TI - Identification and characterization of a pore-forming protein of human peripheral blood natural killer cells. AB - We show here that human peripheral blood NK cells contain a pore-forming protein (PFP) with an Mr of 70,000-72,000 that assembles structural lesions (with an average internal diameter of 150-170 A) and forms functional channels. The PFP was isolated by affinity chromatography from human NK cells, using a specific anti-C9 antiserum as the immunoadsorbent. The NK cells were isolated from PBL by positive or negative selection by indirect rosetting using a panel of monoclonal antibodies directed against different NK and T cell surface antigens. PFP was identified in NK cells freshly isolated and isolated from cultured PBL, both stimulated with interleukin 2, but not in NK cell-depleted lymphocytes. In planar bilayers, the channels formed by the NK cell-derived PFP are highly voltage resistant, with most channels persisting in the open state once they have inserted into the bilayer. The unit conductances of these channels range 0.3-1 nS in 0.1 M NaCl. The channels show poor selectivity for monovalent and divalent ions. The PFP is also released from human NK cells stimulated with the calcium ionophore A23187, suggesting that this protein, like the one produced by murine CTL lines, may be similarly secreted during cell-mediated killing. Its identification in primary human NK cell cultures indicates that this protein may play an active role in NK cell-mediated killing. PMID- 3097240 TI - Gamma interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, interleukin 1, and urokinase genes, which are controlled by short-lived repressors. AB - Exposure of mouse resident and thioglycollate-elicited peritoneal macrophages to IFN-gamma leads to a marked increase in the TNF-alpha (tumor necrosis factor/cachectin), IL-1 and u-PA (urokinase-type plasminogen activator) mRNA levels. Nuclear run-on experiments show that IFN-gamma acts by enhancing the transcription of these three genes. Transcription of these three genes is also rapidly and transiently induced by cycloheximide, an inhibitor of protein synthesis, indicating that they are under the control of short-lived repressors. PMID- 3097242 TI - Immunoturbidimetric measurement of transferrin. AB - This paper describes the development of an automated immunoturbidimetric assay for transferrin on a centrifugal analyser. Regression analysis of transferrin values measured immunoturbidimetrically demonstrates good agreement with data obtained by radial immunodiffusion (y = 0.997 + 0.024 g/l, r = 0.980, n = 50). The assay has a detection limit of 1.0 g/l and working range of approximately 1.0 to 6.0 g/l of transferrin. Day-to-day coefficient of variation is less than 3.5%. Immunoturbidimetric transferrin (g/l) and total iron binding capacity values (mumol/l) were compared using an established total iron binding capacity method (y = 0.050 X - 0.030 g/l, r = 0.967, n = 50). Minimal interference was found for lipaemic, haemolysed or icteric samples. Transferrin reference values with a mean of 3.05 g/l and 95% limits from 2.45 to 3.65 g/l were derived using serum from 300 apparently healthy subjects (150 males, 150 females). We conclude that the proposed transferrin method is more reliable and easier to perform than presently available total iron binding capacity methods. PMID- 3097243 TI - Comparison of tests for streptococcal pharyngitis. AB - Rapid streptococcal antigen detection tests are now an alternative to throat cultures for diagnosing group A streptococcal pharyngitis. By applying existing knowledge to 1,000 theoretical patients, this study compares the diagnostic accuracy, costs, and benefits of "gold standard" throat cultures, less specific office cultures, and rapid streptococcal tests. With the new rapid tests, appropriate treatment for streptococcal pharyngitis can be started promptly without waiting for a culture result. Benefit-cost analysis of existing data shows that rapid tests have the potential to be more efficient than throat cultures in minimizing medical costs and time lost because of illness. These conclusions remained true over widely ranging assumptions about streptococcal prevalence, carrier rate, rheumatic fever attack rate, test cost, and test accuracy. PMID- 3097244 TI - Population frequencies of carbonic anhydrase II (CA II), esterase D (EsD), and glyoxalase I (GLO) in the Metropolitan Birmingham, Alabama area. AB - Both black and white populations from Birmingham, Alabama were analyzed for the frequencies of carbonic anhydrase II (CA II), glyoxalase I (GLO) and esterase D (EsD) isoenzymes. The results compared favorably with published frequencies of these genetic markers in other populations. PMID- 3097245 TI - Electrophysiological study of Drosophila rhodopsin mutants. AB - Electrophysiological investigations were carried out on several independently isolated mutants of the ninaE gene, which encodes opsin in R1-6 photoreceptors, and a mutant of the ninaD gene, which is probably important in the formation of the rhodopsin chromophore. In these mutants, the rhodopsin content in R1-6 photoreceptors is reduced by 10(2)-10(6)-fold. Light-induced bumps recorded from even the most severely affected mutants are physiologically normal. Moreover, a detailed noise analysis shows that photoreceptor responses of both a ninaE mutant and a ninaD mutant follow the adapting bump model. Since any extensive rhodopsin rhodopsin interactions are not likely in these mutants, the above results suggest that such interactions are not needed for the generation and adaptation of light induced bumps. Mutant bumps are strikingly larger in amplitude than wild-type bumps. This difference is observed both in ninaD and ninaE mutants, which suggests that it is due to severe depletion of rhodopsin content, rather than to any specific alterations in the opsin protein. Lowering or buffering the intracellular calcium concentration by EGTA injection mimics the effects of the mutations on the bump amplitude, but, unlike the mutations, it also affects the latency and kinetics of light responses. PMID- 3097247 TI - Human interferon alpha and gamma production by lymphocytes during the generation of influenza virus-specific cytotoxic T lymphocytes. AB - We analysed the production of interferons (IFN)-alpha and -gamma during the generation of human influenza-virus specific cytotoxic T lymphocyte (CTL) responses using monoclonal antibodies in a specific radioimmunoassay. The results showed that the peripheral blood mononuclear cells (PBM) of all donors tested produced IFN-gamma and had influenza A virus-specific CTL activity after stimulation. The amount of IFN-gamma produced and the level of CTL activity were significantly correlated. The PBM of some donors also produced IFN-alpha. The level of IFN-gamma produced was low during the first few days and increased subsequently, but IFN-alpha, when it was detected, was produced on day 1. The kinetics of the increase in IFN-gamma correlated with the increase in CTL activity. We also observed an increased percentage of cells bearing interleukin-2 receptors, which may have been a response to the production of IFN-gamma. The T cells active in lysing influenza A virus-infected target cells and in producing IFN-gamma were determined after separating effector cells with monoclonal antibodies. The CTL effector cells were mainly in the T8+ subset, but IFN-gamma producing cells were found in both T4+ and T8+ subsets. These results suggest that influenza virus-specific T8+ CTL produce IFN-gamma in response to virus, and that T4+ cells which are not CTL effectors also produce IFN-gamma after restimulation with influenza A virus-infected cells. PMID- 3097246 TI - Light-dependent binding of G-protein to outer segment membranes of toad photoreceptors. AB - Light-dependent changes in the binding of G-protein were analyzed in outer segment disk membranes obtained from photoreceptors of the toad (Bufo marinus) retina. Isolated, intact retinas, incubated in oxygenated Ringer's solution at 23 +/- 1 degree C, were subjected to various conditions of illumination and then incubated in darkness for specified periods. The retinas were then chilled (0-4 degrees C) and the receptor outer segments (ROS) were isolated. Binding of the alpha- and beta-subunits of G-protein to the ROS membranes was analyzed by quantitating G alpha and G beta extracted from the membranes with hypotonic medium lacking GTP vs. hypotonic medium containing GTP (H and HG extracts, respectively). For retinas illuminated and then immediately chilled for analysis, the extent of G binding (relative abundance of G alpha, beta in the HG extract) increased with the extent of bleaching of the visual pigment. Near-maximal binding was observed after bleaches of greater than or equal to 30%. With an increasing period of incubation in darkness after approximately 70% bleaching, the extent of binding declined gradually to low levels characteristic of unbleached retinas. The period required for half-completion of the decline was approximately 10(3) s. A gradual decline in G binding, from a rapidly developing peak value, was also observed with an increasing period of exposure to intense light. Viewed in the context of previous electrophysiological data, our results indicate that sustained bleaching desensitization of the rods does not depend upon a persisting state of "tight binding" (immobilization) of G-protein by bleached visual pigment. PMID- 3097248 TI - 5-HT agonist induced analgesia modulated by central but not peripheral noradrenaline depletion in rats. AB - The antinociceptive effect elicited by the 5-hydroxytryptamine (5-HT) agonist 5 methoxy-N,N-dimethyltryptamine (5-MeODMT) was reversed or blocked in animals which had previously sustained severe spinal noradrenaline (NA) depletion via either systemic N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4), neonatal 6-hydroxydopamine (neon. 6-OHDA), or intrathecal 6-OHDA treatment. Biochemical analysis of the lumbar spinal cord samples confirmed severe central NA depletions. Animals were tested with nondamaging heat pain (tail-flick test, hot-plate test) and electric footshock titration to determine the amount of antinociception or nociception. Peripheral NA depletion following intravenous (i.v.) 6-OHDA injection to adult rats had no effect on the antinociception induced by 5-MeODMT, but did cause severe NA depletions in the left heart atrium. These results suggest a modulatory effect of central and not peripheral noradrenergic system upon 5-HT agonist induced analgesia, and also give evidence that this effect is spinally mediated. PMID- 3097249 TI - Possible melatonin involvement in the hypotensive effect of MAO inhibitors. AB - Effect of selective inhibitors of MAO-A and B isoenzymes on pineal melatonin (and related indoles), arterial blood pressure and brain MAO-A and B activities has been evaluated in intact, pinealectomized and sham-operated rats. Selective inhibition of MAO-A but not MAO-B activity stimulated pineal melatonin synthesis and decreased arterial blood pressure in intact and sham-operated animals. Pinealectomy attenuated the hypotensive effect of MAO-A inhibition. The possible melatonin contribution to both antidepressive and hypotensive effects of MAO inhibitors is discussed. PMID- 3097250 TI - Effects of afternoon injections of O-acetyl-5-methoxytryptophol, melatonin or 5 methoxytryptophol in female Syrian hamsters. AB - Female Syrian hamsters were maintained in a 14:10 light: dark photoperiod (lights on 6 a.m.) and injected each afternoon between 4 p.m. and 6 p.m. with diluent or with 25 micrograms melatonin, O-acetyl-5-methoxytryptophol (aML) or 5 methoxytryptophol (ML). After 7 or 12 weeks of treatment, only the melatonin treated hamsters were acyclic. Gross inspection of their ovaries revealed that they were smooth, brown, and devoid of corpora lutea and large follicles. Progesterone levels of the acyclic animals were midway between the high levels observed during estrus and postestrus and the low levels observed on cycle days 2 and 3. Additionally, the melatonin-treated hamsters had significantly reduced uterine weights and pituitary and plasma levels of prolactin. Hamsters treated with aML had significantly lower pituitary prolactin and plasma and pituitary levels of LH only at the 7 week timepoint. ML-treated hamsters had lower pituitary prolactin levels also at 7 weeks. The endocrine changes wrought by injections of aML and ML, however, were insufficient to ultimately affect vaginal cyclicity. In conclusion, it would appear that at the dose used and the time administered melatonin is the more active of the indoles tested in the female hamster, at least in terms of alterations in reproductive physiology. PMID- 3097251 TI - Enhancement of estradiol-induced DNA synthesis in the anterior pituitary gland by the peripheral-type benzodiazepine receptor ligand Ro 5-4864. AB - The effects of peripheral (Ro 5-4864) and central-type (Ro 15-1788) benzodiazepine receptor ligands on estrogen-induced DNA synthesis in the rat anterior pituitary gland was investigated. As expected, a single injection of estradiol (250 micrograms per rat) significantly increased the uptake of 3H thymidine by anterior pituitary cells. Additional treatment with Ro 5-4864 potentiated the effects of estradiol on pituitary DNA synthesis. Under the same experimental conditions, no effect of Ro 15-1788 and sodium valproate, a GABA transaminase inhibitor, was detected. These findings indicate the involvement of peripheral-type benzodiazepine receptors in the control of anterior pituitary cell proliferation. PMID- 3097252 TI - Inhibitory effects of the pineal hormone melatonin and underfeeding during the promotional phase of 7,12-dimethylbenzanthracene-(DMBA)-induced mammary tumorigenesis. AB - The effects of melatonin (Mel) and/or underfeeding (30% food restriction) on 7,12 dimethylbenzanthracene (DMBA)-induced mammary tumorigenesis were examined in female Sprague-Dawley rats fed a semipurified diet. During the promotional phase of tumorigenesis, the animals began receiving either daily afternoon Mel (250 micrograms) or saline vehicle injections s.c. for 15 weeks. As compared with fed animals, underfed rats had a lower tumor incidence, tumor number and size while the latency to onset and regression of tumors was increased. Melatonin in fed rats moderately suppressed tumor incidence and number. However, the combination of Mel treatment and underfeeding caused the most marked inhibition of tumorigenesis as compared with either treatment alone. These results indicate that Mel administration and/or underfeeding during the promotional phase inhibit DMBA-induced mammary tumorigenesis perhaps via neuroendocrine and/or peripheral endocrine mechanisms. PMID- 3097253 TI - The effect of different photoperiods on the methylating capacity of the pineal gland of adult, male golden hamsters, with special reference to 5-methoxyindoles. AB - Testes weight, plasma FSH and LH concentration and pineal methylating capacity were compared in hamsters housed under either long (LD14:10) or short (LD8:16) photoperiods. Hamsters housed for 14 weeks under short photoperiod showed gonadal atrophy, which was complete after 6 weeks. Also plasma FSH and LH concentration showed a marked decline after transfer to short photoperiod. However, after 14 weeks the concentration of FSH and LH as well as testes weight increased again. Under both photoperiods day/night rhythms in plasma FSH and LH concentration were measured. Under both light regimes the concentrations did not show significant differences. Under long as well as short photoperiods in the pineal gland of animals no significant differences were found in the daily synthesis of various MI tested. Only the synthesis of ML was significantly higher in the pineal of hamsters housed under short photoperiod. The function of this higher synthesis of ML remains unknown. Although the maxima of the rhythm for the various MI found under different LD regimes did not differ in magnitude or duration, their location in respect to the onset of darkness was different. It is suggested that this specific location is of more physiological importance than the quantity or duration of synthesis, concentration or release of MI. At the moment the day/night rhythms were determined there were indications that recrudescence of the testes had already started. It is suggested that this recrudescence is responsible for the fact that no differences in the synthesis of MI were found comparing the influence of both photoperiods. After 14 weeks of exposure to short photoperiod, aML synthesis was, in contrast to the synthesis of the other MI, (not significantly) higher under LD8:16. Moreover, opposite results for aMT and aML synthesis during darkness were found. It is suggested that the ratio of synthesis of these compounds is of physiological significance. PMID- 3097254 TI - (-)Deprenyl in perspective: prophylaxis for Parkinson's disease? AB - Idiopathic Parkinson's disease may derive from the action of an environmental 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-like compound. Monoamine oxidase (MAO) B converts MPTP to an actual neurotoxin, 1-methyl-4 phenylpyridinium (MPP+) whilst prior administration of an MAO B inhibitor, ( )deprenyl, prevents the conversion. There is preliminary evidence that this drug can interrupt the pathological process in Parkinson's disease and prolong life expectancy. Thus, markers should be sought to identify the premorbid parkinsonian condition, prior to long-term (-)deprenyl treatment. Possibly approaches are by monitoring putative overactivity of the dopamine degrading enzymes, phenolsulphotransferase and MAO B, narrowing the field down further by PET-scan after administering a positron-emitting dopa analogue, 6-18F-labelled dopa. PMID- 3097255 TI - Pharmacological approaches to Parkinson's disease in the different phases of evolution. AB - The pharmacological approaches to Parkinson's disease in the different phases of evolution (initial or slight, complete and complicated) are discussed. The modality of confronting the therapeutic approach according to the different evolutive phases makes it possible to personalize the therapy, in an attempt to obtain the optimal clinical effect with minimum side effects. Various drugs available and future perspectives are considered. PMID- 3097256 TI - Effect of (-)deprenyl in long-term treatment of Parkinson's disease. A 10-years experience. AB - The effect of (-)deprenyl as additive to a Madopar treatment of parkinsonian patients has been investigated in a retrospective study over the past ten years. 941 patients have been evaluated. Addition of (-)deprenyl to the standard Madopar treatment resulted in an improvement of the disability, in a prolongation of life expectancy, in a reduction of side effects caused by Madopar and a leveling down of the fluctuations in the clinical improvement. In addition the time from the onset of Parkinson's disease to significantly longer in the group of patients which were treated with Madopar and (-)deprenyl in combination. PMID- 3097257 TI - The role of MAO-b inhibitors in the treatment of Parkinson's disease. AB - The classical treatment of Parkinson's disease (PD) using L-dopa plus a peripheral decarboxylase inhibitor (DI) often leads after 3-5 years to the onset of the so-called long-term L-dopa syndrome (LTS). LTS could depend on the chronic overload of L-dopa + ID and could be due to a consequent "receptor disease" and derangement of the neuronal functionality mainly in regard to the enzymatic chains, storage mechanisms and hyperactivity of the monoamine oxidase type B (MAO B). Deprenyl is a selective MAO-B inhibitor thought to be able to slow down the catabolism of dopamine and therefore to allow a decrease of the therapeutic regimen of L-dopa while in the meantime to obtain a more stable plasma and tissue levels and a constant therapeutic response. 76 parkinsonian patients were studied. Their L-dopa regimen was halved and 10 days after (-)deprenyl was added. After the decrease of L-dopa therapy a worsening of symptomatology was observed as expected. The association with (-)deprenyl was able to reverse this trend and when the inhibition of MAOB was really effective patients showed an improvement of symptoms even when compared to baseline values. No relevant side effects were observed and no patients dropped out. PMID- 3097258 TI - (-)Deprenyl in Parkinson's disease: a two-year study in the different evolutive stages. AB - Seventy-nine patients with idiopathic Parkinson's disease in various phases of evolution of the clinical picture were studied. All the patients, already under treatment with L-dopa + PDI, were treated with (-)deprenyl at the dose of 10 mg/day orally in two daily administrations. The mean follow-up was 8.7 months (range, 1-29). Overall, 47.6% of the patients improved, 27.4% showed a marked improvement, 38.1% showed evident modifications, and 27.4% worsened. Sixteen patients were excluded from the study for various reasons. In 53.2% of the cases it was possible to reduce the daily L-dopa dose by a mean of 30%. Overall, ( )deprenyl was effective in the treatment of our parkinsonian patients in the various conditions evaluated, and thus constitutes a new therapeutic strategy for Parkinson's disease. PMID- 3097259 TI - (-)Deprenyl in the treatment of decompensated Parkinson's disease. AB - Two main forms of declining motor performance are evident in Parkinson's disease: response fluctuations and "loss of benefit", i.e., the progression of the disease without "on-off" symptoms. (-)Deprenyl has a favourable beneficial effect in reducing the mild forms of response fluctuations. The addition of (-)deprenyl in such patients to the continuing substitution therapy prevents the development of more severe "on-off" manifestations. In severely disabled patients with irregular response swings or permanent akinesia the use of (-)deprenyl as an adjuvant drug cannot modify anymore the course of the disease. PMID- 3097260 TI - Primate-rodent 3H-MPTP binding differences, and biotransformation of MPTP to a reactive intermediate in vitro. AB - Specific binding of 3H-MPTP to brain homogenates is displaced predominantly by MAO-A inhibitor clorgyline in rat, and by MAO-B inhibitor deprenyl in monkey. A covalently bound metabolite is formed by MAO-B in vitro from MPTP, through a reaction almost completely inhibited by physiological concentrations of glutathione and significantly reduced by other sulfhydryl containing compounds. The difference in binding site pharmacological properties may account for the relative resistance of rat to the neurotoxic effect produced by MPTP in primates. The glutathione-prevented metabolic conversion to a reactive intermediate may be important for the mechanism of MPTP neurotoxicity and relevant to idiopathic Parkinson's disease. PMID- 3097261 TI - Hydrogen peroxide enhances the activity of monoamine oxidase type-B but not of type-A: a pilot study. AB - The effect of hydrogen peroxide on monoamine oxidase (MAO) activity has been determined in homogenates of human brain areas taken postmortem. It could be shown that hydrogen peroxide enhances significantly the activity of MAO-B after short-term incubation (2 min), while no changes have been noted after long-term preincubation (60 min) indicating reversibility of this effect. MAO-A activity was not changed or decreased after preincubation with hydrogen peroxide. Freezing and thawing procedures did not change hydrogen peroxide stimulation of MAO in the caudate nucleus, while MAO-A activity dose dependently decreased. Inhibition of hydrogen peroxide stimulated MAO-B activity in human cortex by (-)deprenyl was found to be of similar potency compared to hydrogen peroxide free estimations. Glutathione, ascorbic acid and mannitol did not block MAO stimulation by hydrogen peroxide, while sodium azide led to a complete inhibition of hydrogen peroxide derived MAO activitation. Interorgan comparison showed increase of MAO-B activity in crude mitochondrial fractions of rat liver after preincubation with hydrogen peroxide, while with rat heart a reduction of MAO activity was detectable. As a conclusion these data indicate a possible role of hydrogen peroxide in the age dependent increase of MAO-B in platelets and brain. Furthermore, increase of cytotoxic hydrogen peroxide via combined L-dopa therapy cannot be excluded to be of importance in the appearance of adverse reactions after long-term treatment with high doses. To reduce hydrogen peroxide production due to MAO activity, a combined treatment of L-dopa plus a selective MAO inhibitor and eventually additional administration of radical scavengers (ascorbic acid, vitamin E etc.) seems to be indicated. PMID- 3097262 TI - The pharmacology of (-)deprenyl. AB - (-)Deprenyl (Selegilinum hydrochloricum, Jumex, Eldepryl) developed in the early sixties as a new spectrum, potent, irreversible MAO blocker (Knoll et al., 1965) was introduced as the first selective inhibitor of B-type MAO (Knoll and Magyar, 1972). In striking contrast to MAO inhibitors which strongly potentiate the pressor effect of tyramine, (-)deprenyl was described to inhibit the tyramine induced release of noradrenaline in vascular smooth muscle (Knoll et al., 1968). The peculiar pharmacological spectrum of (-)deprenyl allowed its use as an adjuvant to the levodopa therapy of Parkinson's disease (for review see Birkmayer and Riederer, 1985). Levodopa therapy revolutionized the medication of Parkinson's disease, but severe side-effects forced the search for adjuvants with a levodopa-sparing effect. Peripheral decarboxylase inhibitors are now efficiently used for this purpose. It was reasonable to expect further potentiation and prolongation of the effect of levodopa in parkinsonians with concurrent administration of MAO inhibitors. A number of irreversible inhibitors of this type were tested in combination with levodopa, and potentiation of the antiakinetic effect of the latter was demonstrated; however, the supervention of distressing side-effect (greatly increased involuntary movements, hypertensive reactions, toxic delirium) terminated any further work along this line. There was a concensus that to give MAO inhibitors concurrently with levodopa was contra indicated. This conclusion was called in question, however, by the development of deprenyl. (-)Deprenyl is a safe MAO inhibitor which can be given concurrently with levodopa and a peripheral decarboxylase inhibitor for the long run without the supervention of any distressing side-effects. For details regarding the pharmacology of (-)deprenyl we refer a number of reviews (Knoll 1976, 1978, 1980, 1982, 1983, 1986). The aim of this paper is to give a brief survey of the most important experimental data which demonstrate that (-)deprenyl facilitates dopaminergic tone in the brain in a peculiar manner and gives a satisfactory explanation for the observation that long-term (-)deprenyl treatment prolongs the life span of parkinsonian patients significantly (Birkmayer et al., 1985). PMID- 3097263 TI - Pharmacology of MAO B inhibitors: mode of action of (-)deprenyl in Parkinson's disease. AB - The selective monoamine oxidase (MAO) type B inhibitor has proven to be a useful adjunct to L-dopa therapy of Parkinson's disease. Although not all features of its anti-Parkinson action is known, studies on brains obtained at autopsy from patients on (-)deprenyl show that the selective inhibition of MAO B with a concomitant increase of dopamine, but not of serotonin, in the basal ganglia may be responsible for its mode of action. The increased life expectancy noted in Parkinsonian patients on long term (-)deprenyl therapy (9 years) is another unexpected feature of the drug (Birkmayer et al., 1985). This exciting data, if confirmed in other long term clinical trials, may herald a new approach for the treatment of this degenerative disease, since more recent studies indicate that Parkinson's disease may eventually turn out to be a neurotoxic event (see Snyder and D'Amato, 1986, for review). Thus selective MAO type B inhibitors could represent a unique class of drug, having both therapeutic and preventive actions in one. PMID- 3097264 TI - Biosynthesis of antibiotics of the virginiamycin family, 5. The conversion of phenylalanine to phenylglycine in the biosynthesis of virginiamycin S1. AB - Conversion of L-phenylalanine to L-phenylglycine in the biosynthesis of virginiamycin S1 (1) can, in principle, take place with intramolecular nitrogen transfer or with intermolecular nitrogen transfer. A labeling experiment with DL [3-13C, 15N]phenylalanine showed that the resulting L-phenylglycine contained no labeled nitrogen, indicating that the rearrangement proceeds via an intermolecular pathway. PMID- 3097265 TI - Effects of phenolic constituents from the mulberry tree on arachidonate metabolism in rat platelets. AB - The effects of various phenolic compounds isolated from the rootbark of the mulberry tree on rat platelet cyclooxygenase and lipoxygenase products formed from (1-14C)arachiodonic acid were studied. Kuwanons G and H, sanggenon C, and mulberrofuran Q at concentrations of 10(-3) to 10(-4)M inhibited the formation of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and thromboxane B2 (cyclooxygenase products); however, they increased the formation of 12-hydroxy-5,8,10,14 eicosatetraenoic acid (12-HETE) (a lipoxygenase product). Sanggenon D and mulberrofuran J at concentration of 10(-3)M inhibited the formation of HHT, thromboxane B2, and 12-HETE. Mulberrofuran G at a concentration of 10(-3)M inhibited the formation of HHT, thromboxane B2, and 12-HETE, while at 10(-5)M, it inhibited the formation of 12-HETE without affecting the formations of HHT and thromboxane B2. Kuwanon M and mulberroside A did not affect arachidonate metabolism in rat platelets. PMID- 3097266 TI - Spectral analysis of the CSF pulse wave at different locations in the craniospinal axis. AB - The frequency spectrum and the amplitude transfer function from arterial pulse pressure to the CSF pulse wave were estimated in the lateral ventricle, cisterna magna and lumbar subarachnoid space of anaesthetised ventilated cats under various conditions: (a) normal status, (b) inhalation of 5% CO2 and (c) saline infusion into the CSF space (0.045 ml/min). The CSF pulse waveforms in the lateral ventricle and cisterna magna were almost identical in all conditions. Inhalation of CO2 and saline infusion increased the values of the amplitude transfer function from blood pressure to the CSF pulse wave in the lateral ventricle and cisterna magna to a similar extent. The CSF pulse in the lumbar sac was remarkably damped under both normal conditions and during CO2 inhalation, but the damping was diminished by saline infusion. During the saline infusion, the spinal canal appeared to function as a low-pass filter to the conduction of the CSF pulse. PMID- 3097267 TI - Hypotensive effect of long-term oral calcium supplementation in elderly patients with essential hypertension. AB - Calcium gluconate (22.4 g/day; 2 g/day as Ca) was administered orally for 8 weeks to eight hospitalized elderly patients with essential hypertension in order to confirm the hypotensive effect of oral calcium supplementation and to clarify its hypotensive mechanism by analyzing changes in hormonal factors. After 2 weeks of calcium supplementation, both systolic and diastolic pressures decreased significantly and remained decreased for the duration of the study. An elevation of plasma PGE2 correlated with blood pressure reduction was observed at 2 weeks. Plasma norepinephrine decreased significantly from 4 weeks. Plasma parathyroid hormone decreased significantly from 4 weeks, and 1,25-dihydroxyvitamin D (1,25 [OH]2D) decreased significantly at 8 weeks. The reduction of plasma 1,25-(OH)2D correlated with blood pressure decrease at 8 weeks. The present study indicates that the mechanism of its hypotensive effect is multifactorial and may be different during different phases of calcium supplementation. The suppression of plasma 1,25-(OH)2D following reduction of parathyroid hormone may be involved in the hypotensive effect in the chronic phase of calcium supplementation. Enhancement of PGE2 production in the early phase and suppression of sympathetic nervous activity in the chronic phase may also be factors in blood pressure reduction. PMID- 3097268 TI - Dedicated monitoring of anesthetic and respiratory gases by Raman scattering. AB - The monitoring of respiratory and anesthetic gases in the operating room is important for patient safety. This study measured the accuracy and response time of a multiple-gas monitoring instrument that uses Raman light scattering. Measurements of oxygen, carbon dioxide, nitrogen, nitrous oxide, halothane, enflurane, and isoflurane concentrations were compared with a gas mixer standard and with measurements made with an infrared anesthetic agent analyzer. Correlation coefficients were all greater than 0.999, and probable errors were less than 0.43 vol% for the gases and less than 0.03 vol% for the volatile anesthetics. Response time was 67 ms with a sample flow rate of 150 ml/min. There was some signal overlap between nitrogen and nitrous oxide and between the volatile anesthetic agents. Such overlap can be compensated for by linear matrix analysis. The Raman instrument promises a monitoring capability equivalent to the mass spectrometer and should prove attractive for the monitoring of respiratory and anesthetic gases in the operating room. PMID- 3097269 TI - Continuous monitoring of mixed venous oxygen saturation in septic shock. AB - Fiberoptic pulmonary artery catheters provide a practical method for continuously measuring the amount of oxygen in mixed venous blood. To characterize the usefulness of mixed venous oxygen saturation in managing patients with sepsis, we performed serial hemodynamic measurements on 20 patients with documented septic shock. There was a highly significant positive correlation between increases or decreases of 5% or more in mixed venous oxygen saturation and corresponding changes in oxygen delivery (r = 0.95) and oxygen consumption (r = 0.96). Mixed venous oxygen saturation less than 65% was clinically unacceptable in patients with sepsis and was associated with a poor prognosis. In this study, measurement of mixed venous oxygen saturation was a valuable predictor of survival in patients with septic shock and provided a means of continuously monitoring the status of tissue oxygenation. PMID- 3097270 TI - Do we monitor enough? We monitor too much. AB - Not only may we monitor too much, we also may monitor improperly. By so doing we divert attention from the patient and the anesthetic and thereby often decrease the quality of care. Furthermore, the teaching of residents can be impeded by an overemphasis on monitoring, resulting in a wrong sense of values. The cost of monitoring is high, not only in financial terms, but also in terms of the time devoted to machines, electrodes, and sensors, and in terms of complications such as shearing, infections, vasospasm, hematomas, and even fatal hemorrhage. Not all monitoring is bad, however. Oxygen, temperature, blood pressure, and the electrocardiogram should be monitored, but we must avoid a lavish concept that monitoring will solve all our problems and eliminate the need for proper personal attention. Most important, we must avoid the notion that more monitoring is categorically better. PMID- 3097271 TI - A simple automatic record of oxygenation and ventilation with a pulse oximeter and a carbon dioxide monitor. AB - Many cases have come to medicolegal attention in which a healthy patient undergoing a routine, elective operation has had an unexpected cardiac arrest attributed to hypoxia or hypercarbia. A simple, objective, automatic, inexpensive record of the adequacy of oxygenation and ventilation was obtained by using the Nellcor N-100 pulse oximeter, the Puritan-Bennett/Datex carbon dioxide monitor, and the Nellcor N-9000 recorder in combination. The required interface is described, and a sample record is presented. A second interface allows the recorder to work with the Puritan-Bennett anesthesia and brain activity monitor (ABM-1). Oxygen saturation can also be displayed on the video screen of the anesthesia and brain activity monitor. PMID- 3097272 TI - Coding of the spatial period of gratings rolled across the receptive fields of somatosensory cortical neurons in awake monkeys. AB - In order to measure the texture coding capabilities of motion-, direction-, and orientation-sensitive neurons in SI cortex, we rolled wheels with surface milled gratings across their receptive fields. Gratings of spatial periods 0.8-9.6 mm were presented in pseudorandom order; each was tested 5-20 times in the distal, proximal, radial, and ulnar directions. Thirty eight cortical neurons were studied with three to eight different gratings in order to determine the effect of spatial period on neuronal firing rates. While all 38 cells had their firing rates modulated by motion of the gratings, only 11 neurons were able to distinguish changes in its spatial period. These cells had small receptive fields located on the hand. Most motion-sensitive neurons showed little effect of spatial period on firing rates and had relatively flat frequency response curves. One showed decreased firing to spatial periods over the range 0.8-6.4 mm; three others increased their firing rates over the range 0.8-3.2 mm, followed by a decline in activity to larger spatial periods. Direction- and orientation sensitive neurons showed only minor changes in firing rates as a function of spatial period. Sixteen cells showed flat frequency response functions, three showed increased firing rates, and four decreased firing rates as spatial period of the grating increased. Direction and orientation preferences were maintained over the range 0.8-9.6 mm for all 23 neurons tested. Although four cells showed a drop in direction index (DI) as the spatial period was increased, none showed a loss of direction sensitivity, as DI was greater than 35 for all gratings tested. Two neurons showed increased firing to motion in the last-preferred direction and two others decreased firing in the best direction. The remaining 19 neurons showed parallel effects of texture in all directions. Some motion-sensitive neurons showed weak direction preferences when tested with fine gratings; these preferences disappeared with coarser gratings, due to increased responsiveness to motion in the least-preferred direction. These data demonstrate that movement sensitive neurons do not require continuous trajectories across the skin but instead sequential activation of points aligned in a specific path. Cortical neurons appear capable of integrating information from points separated by up to 9 mm, as long as they are presented in the appropriate temporal sequence. Firing rates of direction- and orientation-sensitive neurons are more profoundly modified by changes in the direction of motion across the skin, and the temporal order of stimulation, than by alterations in the spatial characteristics of the moving stimulus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3097273 TI - Tactile detection of a dot on a smooth surface: peripheral neural events. AB - The capacities of humans to detect the presence of a single raised dot of 550 micron diameter on a smooth plate and to judge the magnitude of evoked sensation were determined for dots of different heights, stroked at different velocities across the passive fingerpad. Evoked responses to the same stimuli were recorded from single, slowly adapting (SA), rapidly adapting (RA), and Pacinian (PC) mechanoreceptive peripheral nerve fibers innervating the fingerpad of anesthetized macaque monkeys. When the stroke velocity was 10 mm/s, dot height detection thresholds, as determined from measurements of detection sensitivity were between 1 and 3 microns for all human observers. From fiber recordings in monkeys, the RAs had dot height thresholds of 2-4 microns, i.e., within the range of human detection thresholds. The dot height thresholds were 8 microns or greater for SAs and 21 micron or greater for PCs. In contrast, force thresholds for punctate von Frey filaments did not differ for RAs and SAs and were lowest for PCs. The magnitude of sensation evoked in human increased with increases in dot height above threshold. Similarly, the number of nerve impulses evoked in monkey RAs increased with dot height as did the widths of RA receptive fields. Neither changes in stroke velocity from 10 to 40 mm/s nor changes in vertical force applied by the dot plate to the skin altered sensory magnitude evoked by a 15-microns high dot or the number of impulses evoked in RAs. However, a decrease in stroke velocity from 10 to 1.5 mm/s elevated sensory detection thresholds and, for the 15-microns high dot, decreased sensory magnitude, the number of impulses in RAs, and the widths of RA receptive fields. It was hypothesized that the mechanical event responsible for activating the RA was the lateral deformation of elevated regions of skin. In support of this, the number of impulses evoked in RAs by a dot was greater when the dot was stroked across, as opposed to along, the papillary ridges. Also, under certain stimulus conditions, a correspondence was observed between the occurrence of each action potential in an RA and the passage of the leading edge of the dot across the peak of a papillary ridge. It is concluded that the responses of RAs alone account for the sensory capacity to detect a dot of minimal height on a smooth surface with the fingerpad.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3097275 TI - Treatment of experimental focal cerebral ischemia with mannitol. Assessment by intracellular brain pH, cortical blood flow, and electroencephalography. AB - Intracellular brain pH, cortical blood flow (CBF), and electrocorticograms were recorded in regions of severe and moderate ischemia in 10 control rabbits and 10 rabbits given mannitol, 1 gm/kg, after occlusion of a major branch of the middle cerebral artery. Pooling the data from all 20 animals, preocclusion CBF was 46.4 +/- 3.6 ml/100 gm/min and intracellular brain pH was 7.01 +/- 0.04 (means +/- standard error of the means). Although mannitol administration mildly improved CBF in regions of severe ischemia, this increase was not sufficient to prevent metabolic deterioration as assessed by brain pH. However, in regions of moderate ischemia, CBF improved significantly with mannitol and the gradual decline in brain pH observed in control animals was prevented. For example, in the treated moderate ischemia sites 4-hour postocclusion CBF and pH values were 31.8 ml/100 gm/min and 6.89 +/- 0.09, respectively, as compared to control values of 14.3 ml/100 gm/min and 6.75 +/- 0.06. These results suggest that mannitol may be of benefit in stabilizing regions of moderate, but not severe, ischemia after vessel occlusion. PMID- 3097274 TI - Receptive field properties and latencies of cells in the lateral geniculate nucleus of the North American opossum (Didelphis virginiana). AB - Relay cells in the lateral geniculate nucleus (LGN) of the North American opossum were classified as types 1, 2, and 3 on the basis of their receptive field properties and afferent latencies to optic nerve (ON) and optic chiasm (OX) stimulation and antidromic latencies to stimulation of cortex. Type 1 and type 3 cells gave transient responses and type 2 cells gave sustained responses to appropriate standing contrast in the receptive field center. The differences in response pattern were quantified with a phasic-tonic index (PTI); the PTI values for type 2 cells (PTI less than 63) did not overlap those for type 1 cells (PTI greater than 68) or type 3 cells (PTI greater than 80). With a homogeneous field (1.3 cd/m2), the maintained discharge rates (spikes/s) of type 3 cells (less than 1-11) were significantly lower than those of type 1 cells (3-23) and of type 2 cells (1-22). For all type 2 cells tested with a counterphased sine-wave grating, a null position of the grating was found and the cells were classified as linear. The type 1 and type 3 cells tested were nonlinear (i.e., exhibited excitatory doubling and did not have a null grating position). The maximum velocity of movement that reliably elicited responses (cut-off velocity) was low for type 3 cells (mean = 29.1 degrees/s) and relatively high for type 1 cells (mean = 70.3 degrees/s). Cut-off velocities for type 2 cells (mean = 61.2 degrees/s) were slightly lower than for type 1 cells. Type 1 cells had relatively short afferent (ON and OX) latencies, fast afferent conduction velocities, and short antidromic (cortex) latencies; type 2 cells had intermediate afferent and antidromic latencies and intermediate afferent conduction velocities; and type 3 cells had relatively long afferent and antidromic latencies and slow afferent conduction velocities. The receptive field center diameters were similar for type 1 (4.2 25.5 degrees; mean = 11.4 degrees) and type 3 cells (2.8-23.7 degrees; mean = 11.0 degrees), whereas the receptive field centers for type 2 cells (2.9-15.1 degrees; mean = 6.9 degrees) were significantly smaller. The majority of type 1 (66.7%) and type 3 cells (63.3%) had on-center receptive fields, whereas the proportion of on-center fields was even greater for type 2 cells (83.0%). Only a few of the cells encountered in the opossum LGN (6%) had on-off receptive fields, and a portion of these could not be shown to be relay cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3097276 TI - Desmoplastic supratentorial neuroepithelial tumors of infancy with divergent differentiation potential ("desmoplastic infantile gangliogliomas"). Report on 11 cases of a distinctive embryonal tumor with favorable prognosis. AB - Eleven cases of supratentorial neuroepithelial tumor presenting in infancy are reported. The tumors were characterized by their voluminous size, their intense desmoplasia, and the frequent presence of divergent astrocytic and ganglionic differentiation as demonstrated by special neurohistological and immunohisto- and immunocytochemical techniques. All the tumors presented in subjects below the age of 18 months, usually within the first 4 months of life. They most often involved the frontal and parietal regions and were composed predominantly of a dense desmoplastic tissue superficially resembling a moderately cellular fibroma. The fibroblastic elements were admixed with variable numbers of pleomorphic neuroepithelial cells. Divergent astrocytic and neuronal differentiation was demonstrable in nine of the 11 tumors. All showed astrocytic differentiation. The study of one example by electron microscopy, immunocytochemistry, and tissue culture disclosed that the astrocytic tumor cells were partly invested by a pericytoplasmic basal lamina. Successful total or near-total surgical resection has been followed by a favorable postoperative course extending in some cases over many years of tumor-free survival. The name "desmoplastic infantile ganglioglioma" is proposed for this apparently distinct clinicopathological entity, whose massive size is indicative of a pre- or perinatal origin. Its identification can be achieved by careful histological analysis and is of obvious prognostic significance. PMID- 3097277 TI - Role of thallium-201 total-body scintigraphy in follow-up of thyroid carcinoma. AB - To evaluate the reliability of total-body scintigraphy using [201Tl]chloride in postoperative follow-up of thyroid carcinoma, this procedure was performed in 326 patients after total thyroidectomy for thyroid carcinoma. The results were compared with those of 131I scintigraphy and thyroglobulin assays. 201Tl total body scintigraphy was found to have the greatest sensitivity (94%), whereas 131I scintigraphy had the highest specificity (99%). It is shown that 201Tl total-body scintigraphy is a useful procedure in follow-up of thyroid cancer, however, the combination of parameters provides the greatest reliability. In medullary thyroid carcinoma, which is usually 131I negative, 201Tl total-body scintigraphy can be of great value for the localization of metastases which are indicated by elevated serum levels of calcitonin and carcinoembryonic antigen. PMID- 3097278 TI - High yield synthesis of 6-[18F]fluoro-L-dopa by regioselective fluorination of protected L-dopa with [18F]acetylhypofluorite. AB - Regioselective fluorination of a completely protected phosgene derivative of 3,4 dihydroxy-phenyl-L-alanine (5-(benzyl-3',4'-carbonate)-oxazolidine-2,5-dione) with gaseous 18F-labeled acetylhypofluorite and [18F]F2 in acetonitrile is described. Fluorination with [18F]acetylhypofluorite yields 6-[18F]fluoro-L-dopa with 95% radiochemical purity; fluorination of the same substrate with [18F]F2 yields a mixture of all three structural isomers in a ratio of 70:16:14 for 6-, 5 , and 2-fluoro compounds. Radiochemical yield, relative to [18F] acetylhypofluorite, measured at the end of the synthesis, is (21 +/- 4)% (N = 8). The synthesis requires approximately 40 min (50 min if HPLC was done) and yields the final radiopharmaceutical in a two-step procedure. The specific activity of the final product was approximately 763 mCi/mmol at the end of a 40-min synthesis when 30-min irradiation was used. PMID- 3097279 TI - Seven-year follow-up of workers exposed to 1,2-dibromo-3-chloropropane. AB - A follow-up report was done of workers exposed to 1,2-dibromo-3-chloropropane (DBCP) 7 years after termination of exposure. A 1977 study of male pesticide workers exposed to DBCP in a California agricultural chemical plant identified many who were azoospermic or oligospermic. Sperm concentration and serum follicle stimulating hormone (FSH) levels in 44 of these workers were reassessed 5 to 8 years after exposure was terminated in 1977. Two of the eight originally azoospermic workers produced sperm during the follow-up, although only one had normal sperm counts. No increase in sperm production could be detected in men who had low sperm counts in 1977, and elevated serum FSH levels did not drop in oligospermic or azoospermic men. These results suggest that permanent destruction of germinal epithelium occurs in most DBCP-sterile persons. PMID- 3097280 TI - Assessment of clinical, metabolic, dietary, and occupational correlations with serum polychlorinated biphenyl levels among employees at an electrical capacitor manufacturing plant. AB - In order to assess the extent of polychlorinated biphenyl (PCB) exposure and potential health effects, a clinical-epidemiologic survey was initiated among 205 workers at a capacitor manufacturing plant. The geometric mean serum PCB level for workers was 18.2 ppb (SD 2.88), with a range of 0 to 424 ppb. Multiple regression analysis found duration of employment, cumulative occupational exposure, cumulative fish consumption, and cholesterol level to be significant predictors of log serum PCB levels. Of these predictors, duration of employment and cumulative occupational exposure were the strongest contributors to the regression model, indicating the dual importance of opportunity for dermal contact and respiratory exposure level in contributing to workers' serum PCB levels. PMID- 3097281 TI - Arachidonic acid-induced brain ischaemia: different severity between stroke resistant spontaneously hypertensive rats and Wistar-Kyoto rats. AB - A thrombo-embolic stroke model was produced by the internal carotid artery (ICA) infusion of arachidonic acid (AA). The differences in responses to AA ICA infusion were investigated in stroke-resistant spontaneously hypertensive rats (SHRSR) and Wistar-Kyoto (WKY) rats. The SHRSR showed a higher mortality, more severe brain oedema and brain metabolic impairment, more prominent elevation of TXB2 and 6-keto-PGF1 alpha. Electron microscopic observation revealed more severe endothelial damage, mitochondrial swelling and perivascular oedema and earlier thrombus formation in SHRSR than in WKY rats. PMID- 3097282 TI - Increased non-collagen protein synthesis in the posterior cerebral artery in spontaneously hypertensive rats. AB - When 3H-proline was administered to spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, its incorporation into non-collagen protein of the posterior cerebral artery or the mesenteric artery was greater in SHR than WKY. Young SHR were treated with either clonidine or 6-hydroxydopamine (6-OHDA). Administration of clonidine decreased the rate of incorporation of 3H-proline into the non collagen protein of these arteries concomitantly with a reduction of blood pressure in each rat strain. Administration of 6-OHDA slightly decreased the incorporation of the proline into the non-collagen protein of the SHR posterior cerebral artery, but failed to reduce blood pressure in each rat strain. Ultrastructural pictures of the posterior cerebral arteries of the SHR showed numerous adrenergic ganglion cells. Thus, neural factors, especially in the cerebral arteries, may regulate vascular protein synthesis and may be important for the initiation of hypertension in SHR. PMID- 3097283 TI - PCBs--an epidemic of concern. PMID- 3097284 TI - Effects of retinyl palmitate on DMBA tumorgenesis in the rat submandibular salivary gland. PMID- 3097285 TI - Effects of mechanical and osmotic pressure on the rate of glycosaminoglycan synthesis in the human adult femoral head cartilage: an in vitro study. AB - We studied the effects of mechanical and osmotic compression on sulphate incorporation into glycosaminoglycans of human femoral head cartilage. We found that both mechanical and osmotic compression produce the same lowering of sulphate uptake relative to uncompressed controls. It appears that this effect is not associated with changes in solute transport or changes in solute concentration in the matrix, but is due, in part at least, to an increased osmotic pressure acting on the chondrocytes. A second mechanism of action might be involved directly through the increased proteoglycan concentration in the pericellular environment, resulting from a reduction in the water content. We also found that glycosaminoglycan synthesis returned to its control level when the conditions prevailing in the matrix, in the absence of pressure or added solute, were restored. PMID- 3097286 TI - Joint reaction to polyethylene implantation: a method for inducing osteoarthritic change and osteophyte formation in the rabbit knee joint. AB - Joint lesions were induced by implantation of a rigid piece of polyethylene sutured under the patella and quadriceps tendon of the rabbit's right knee. Compared to the left sham-operated knee, follow-up studies revealed progressive changes that consisted of early and transient synovial hyperemia and proliferation and late osteoarthritis. By day 7 after surgery, soft synovial-like tissue proliferated around the implant and the articular margins of the femoral trochlea indicating primitive "osteophytic" protuberances (synoviophytes). By day 15 after surgery, the synoviophytes had acquired a more solid consistency and were composed mostly of fibrocartilage covered by a fibro-cellular synovial lining (chondrophytes). By that time, this tissue was invaded with vascular channels; signs of ossification were already present in the deepest layer adjacent to bone. Between the 2nd and 12th weeks, this fibro-cartilaginous tissue, except for the surface fibrous or fibrocartilaginous layer, was progressively replaced by immature bone (osteophyte). Secondary bone remodeling started soon after the first lamellae of immature bone were deposited. Complete integration of the osteophyte into the distal femur occurred during the 2nd and 3rd month. PMID- 3097287 TI - The effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) on fetal mice during pregnancy--with emphasis on implantation and fetal weight. PMID- 3097288 TI - [Oxygen tension in the stria vascularis of the guinea pig cochlea under various conditions]. PMID- 3097290 TI - The pattern of early neuronal differentiation in Drosophila melanogaster. AB - Based on the staining of Drosophila embryos with neuron-specific monoclonal antibodies we describe the differentiation of the earliest neurons in the central nervous system. The metameric array undergoes a number of changes during development that distinguish several morphological units: metameres, neuromeres and ganglia. Neural landmarks in the CNS and the periphery are identified on the bases of their developmental history, axonal projection and segment specificity. A time sequence of differentiation starting in the posterior gnathal and anterior thoracic anlage has been found. PMID- 3097289 TI - Germ-line transformation involving DNA from the period locus in Drosophila melanogaster: overlapping genomic fragments that restore circadian and ultradian rhythmicity to per0 and per- mutants. AB - P-element-mediated transformations involving DNA fragments from the period (per) clock gene of Drosophila melanogaster have shown that several subsegments of the locus restore rhythmicity to per0 or per- mutants. Such fragments overlap in a genomic region complementary to one transcript, a 4.5-kb RNA which is probably the per message, in that it is necessary and (in terms of expression from this X chromosomal locus) sufficient for the fly's circadian rhythms. It is also at least necessary for the high-frequency oscillations normally produced by courting males as they vibrate their wings. The entirety of the 4.5-kb transcript is not necessary for rather strong rhythmicity; nor does it seem to be sufficient, in transformants, for wild-type behavioral phenotypes. A 0.9-kb RNA, homologous to genomic region immediately adjacent to the source of the 4.5-kb species, oscillates in its abundance over the course of a day; but coverage of this transcript source in several transformants carrying a per0 mutation--which eliminates the 0.9-kb RNA's oscillation--does not restore rhythmicity. All of the independently isolated arrhythmic mutations tested were covered by the same array of overlapping per+-derived DNA fragments, implying that the only portion of the locus which has mutated to arrhythmicity is complementary to the 4.5-kb transcript. PMID- 3097291 TI - Role of the optic lobes in the regulation of the locomotor activity rhythm of Drosophila melanogaster: behavioral analysis of neural mutants. AB - The locomotor activity patterns of the Drosophila melanogaster brain mutants optomotor blind (omb), lobula plateless (lop), minibrain (mnb), small optic lobes (sol), sine oculis (so), and the double mutants mnb;so and sol;so, all of which show reductions in the optic lobes, were investigated and compared with those of the wild-type. In none of the mutants was the number of arrhythmic flies significantly higher than in the wild-type, indicating that the optic lobes are not the sole site of a pacemaker controlling the locomotor activity rhythm. However, these mutations greatly influence the stability of the circadian system, in that the number of flies simultaneously showing two or more circadian components increased as the optic lobe defects became more severe. In flies with the strongest reduction of the optic lobes, two free-running circadian components were found almost exclusively. This suggests a two-oscillator control of the locomotor activity. Eyeless mutants also expressing a neural mutation were entrained by light:dark (LD) cycles, but their activity pattern in LD was changed compared to the wild-type and the eyeless mutant so. PMID- 3097292 TI - Gonadotropin-independent isosexual precocity in a boy with tuberous sclerosis: effect of ketoconazole. PMID- 3097294 TI - Immunoglobulins inside Schistosoma japonicum eggs from the livers of mice. AB - Using fluorescent antibody techniques, immunoglobulins (Ig's), mainly IgG class, were detected inside Schistosoma japonicum eggs lodged in mouse liver. Ig's were observed as a focal pattern between the miracidium and the eggshell during early infection (5-7 wk), particularly in lightly infected mice (20 cercariae). With advancement of time of infection (8-18 wk), a diffuse pattern of staining over the miracidial body developed and became predominant. The diffuse pattern of staining could be observed in the eggs taken from heavily infected mice (50 cercariae), during early stage. Eggs showing the focal pattern in a restricted area appeared to be morphologically intact, whereas eggs showing the diffuse pattern exhibited some types of eggshell destruction. We conclude that the focal pattern reflects disintegration of eggs in the initial stage and the diffuse pattern in the advanced stage. This spatial relationship between Ig's and eggs is discussed in relation to destruction of eggs. PMID- 3097293 TI - Enhanced lipid utilization in infants receiving oral L-carnitine during long-term parenteral nutrition. AB - Fourteen infants requiring long-term total parenteral nutrition but able to tolerate small quantities of enteral feedings were randomized into carnitine treatment and placebo control groups. All infants had received nutritional support devoid of carnitine. Plasma carnitine levels and observed plasma lipid indices were not different before supplementation. Under standardized, steady state conditions, 0.5 g/kg fat emulsion (intralipid) was administered intravenously over 2 hours both before and after infants received 7 days of continuous nasogastric or gastric tube L-carnitine (50 mumol/kg/day) or placebo. Plasma triglyceride, free fatty acid, acetoacetate, beta-hydroxybutyrate, and carnitine concentrations were observed at 0 (start of lipid infusion), 2, and 4 hours for pre- and post-treatment periods, and in addition at 6 and 8 hours after carnitine supplementation. Infants receiving carnitine had significantly greater beta-hydroxybutyrate plasma concentrations (P less than 0.05) and carnitine (P less than 0.001) at 0, 2, 4, 6, and 8 hours, and greater plasma acetoacetate concentrations (P less than 0.05) at 2, 4, 6, and 8 hours, compared with controls. Twenty-four-hour urinary carnitine excretion was very low for both groups before supplementation; after supplementation, excretion was higher (P less than 0.05) in the carnitine group. No significant differences were found between groups for plasma triglyceride or free fatty acid concentrations at any observation period. This study demonstrated enhanced fatty acid oxidation, as evidenced by increased ketogenesis, with L-carnitine supplementation in infants receiving long-term total parenteral nutrition. PMID- 3097295 TI - Serum factors from infected baboons inhibit oviposition and cause unpairing of Schistosoma mansoni in vitro. AB - A reliable in vitro fecundity assay for Schistosoma mansoni was established. The main features that reduced variability in in vitro oviposition were pre-selection and randomization of worm pairs producing moderate numbers of eggs in initial 2 day culture, and short pre-incubation in serumless medium prior to addition of test sera to the cultures. In 4 of 6 total experiments testing the effects of serum from chronically infected baboons, significant (P less than or equal to 0.025) fecundity reduction ranging from 29 to 82% was found. Chronically infected baboon serum also caused consistently higher unpairing than normal serum. These results demonstrate the existence of serum factors which inhibit egg production and maintenance of the paired status of Schistosoma mansoni in vitro. PMID- 3097296 TI - Pseudallescheriasis in northern Britain. AB - Five cases of Pseudallescheria boydii infection are reported from the northern part of the United Kingdom. None of the patients had travelled abroad. Three cases of otitis in which P. boydii was associated with bacterial infections were diagnosed within a 6-month period. A lady who had diabetes mellitus presented with a pulmonary fungus ball in a pre-existent cavity caused by a previous bacterial infection. After minor trauma at the site of an old skin graft, a farmer's wife developed an ulcer on the dorsum of the right ankle. Precipitating antibodies were demonstrated except in two of the cases of ear infection. The management of the individual cases is discussed. PMID- 3097297 TI - Effect of co-administration of interferon inducer, polyriboinosinic acid polyribocytidylic acid, with SKF 525-A on hepatic drug metabolizing enzymes of rats. AB - The protective effect of SKF 525-A on the suppression of cytochrome P-450 content and monooxygenase activities by treatment with CoCl2 and polyriboinosinic acid polyribocytidylic acid [poly(I.C] was compared as a part of studies of suppression of drug metabolizing enzymes by interferon inducers. Induction of heme oxygenase activity by CoCl2 and poly (I.C) was not altered by simultaneous treatment with SKF 525-A. Depression of cytochrome P-450 content and benzphetamine N-demethylase activity by treatment with CoCl2 was prevented by co treatment with SKF 525-A. This effect was explained by the prevention of release of heme from cytochrome P-450 by forming metabolic intermediate complexes with metabolites of SKF 525-A. On the other hand, poly(I.C) significantly suppressed P 450 content and benzphetamine N-demethylase and benzo [a] pyrene hydroxylase activities, even under simultaneous treatment with SKF 525-A. This inhibition by poly (I.C) was accompanied by weak staining of proteins corresponding to cytochrome P-450 in SDS gel electrophoresis. In addition, the activity of non heme enzyme, 4-hydroxybiphenyl glucuronyltransferase, was suppressed by treatment with poly (I.C) but not by CoCl2-treatment. These findings strongly suggested that, unlike CoCl2, poly (I.C) suppressed cytochrome P-450 content and monooxygenase activities due to decreased synthesis or increased degradation of the apoprotein of cytochrome P-450 with slight contribution of the induced heme oxygenase. PMID- 3097298 TI - [Effect of 2-ethyl-2-ene-1-al and analogous compounds on the growth and ultrastructure of fungi]. AB - Analogs of the natural substance (E)-hex-2-en-1-al which occurs naturally in green plants and is known to have microbiocidal properties were synthesized and studied with respect to their antifungal properties. Saturated and unsaturated aldehydes, alcohols, carbon acids and enolacetate were tested against various fungi by applying these compounds either over the gaseous phase or in suspension. The following ranking was observed on the basis of fungicidal activity: enolacetate of 2-ethylhex-2-enoic acid greater than 2-ethylhex-2-en-1-al greater than 2-ethylhex-2-en-1-al greater than 2-ethylhex-2-en-1-ol. Saturated analogs showed the same order of activity as the unsaturated ones, however, they were less efficient. The effects on the ultrastructural changes were analyzed in Mucor mucedo exposed to concentrations of the analogs that inhibited growth. Main effects were observed on mitochondrial and nuclear membranes. The kind of destruction caused by enolacetate of 2-ethylhex-2-en-1-al differed from the other substances tested. Aspects of the mode of action are discussed. PMID- 3097299 TI - Reactivity of enprostil stereoisomers in soft elastic gelatin capsules. AB - Enprostil (methyl 7-[(1R*,2R*,3R*)-3-hydroxy-2-[(E)-(3R*)-3-hydroxy-4-phenoxy-1 butenyl]- 5-oxocyclopentyl]-4,5-heptadienoate), a gastric acid secretion inhibitor and potent anti-ulcer drug, is formulated as a propylene carbonate solution which is filled into soft elastic gelatin capsules. The drug molecule features two unresolved asymmetric carbon atoms, and synthesis yields an equimolar mixture of four different optical isomers (two diastereomeric pairs of enantiomers). The objective of this study was to establish the degree to which enprostil does or does not degrade stereoselectively in the soft elastic gelatin capsule formulation. Accordingly, we developed an HPLC method capable of resolving enprostil diastereoisomers and applied the method to determining reaction rates of enprostil in soft elastic gelatin capsules maintained at 40 degrees C. The study included three soft elastic gelatin capsule lots: the first two contained an equimolar mixture of all four enprostil enantiomers; and the third contained an equimolar mixture of two individual diastereoisomers of known optical purity. Comparing enprostil degradation rates in the three capsule lots showed that reactivity ratios in all cases were (within the limits of experimental uncertainty) equal to unity. This observation conclusively excludes the possibility of significant enantioselectivity for enprostil degradation in the soft elastic gelatin capsule formulation. We also report kinetic equations for the general case of relating stereospecific reactivity ratios to drug product shelf life when drug concentrations are monitored with nonstereoselective analytical techniques. PMID- 3097300 TI - [Immunoregulative effects of carnosine and beta-alanine]. AB - Physiological factors involved in immunity and tissue repair with regulate homeostasis, a physiological function of the connective tissue, are as yet unidentified. We earlier detected the granulation-promoting action of carnosine, and reported on the acceleration of tissue repair in experimental as well as clinical studies. In that study, immunoregulatory effects of carnosine and beta alanine were examined by the plaque-forming cell (PFC) count and delayed hypersensitivity reaction (DHR). The PFC value increased in mice pretreated with these agents. In these mice, PFC reaction to 2 X 10(7) SRBC was enhanced but that to 1 X 10(9) SRBC was suppressed. The agents also suppressed excess immunoreaction in immature mice but increased weakened immunoreaction in aged animals. Furthermore, the agents had the optimal doses for the enhancement of both PFC reaction to 1 X 10(8) SRBC and DHR to 1% picryl chloride. They also induced recovery of immunofunction suppressed by the administration of MMC. Carnosine and beta-alanine exerts immunoregulatory effects by activating both T and B cells. Our observations indicated that the agents not only promote tissue repair but also help maintain homeostasis and accelerate spontaneous healing. PMID- 3097301 TI - [Immunoregulative effects of homocarnosine and gamma-aminobuthyric acid]. AB - The effects of homocarnosine and GABA on antibody production (PFC reaction) and cellular immunity (delayed hypersensitivity reaction, DHR) were examined in vivo. In mice treated with these agents, PFC reaction to 2 X 10(7) SRBC was enhanced but that to 1 X 10(9) SRBC was suppressed; moreover, immunoreaction was reduced in immature mice (2-2.5 weeks old) but was increased in aged mice (30 weeks old or above). These agents had optimal doses on the PFC reaction in mice given 1 X 10(8) SRBC and DHR, and induced recovery of immunofunction suppressed by the administration of MMC. PMID- 3097302 TI - re Successful conservative management of chylothorax following cardiomyotomy. PMID- 3097303 TI - Prenatal detection and prevention of neural tube defects in South Wales. PMID- 3097304 TI - A perspective of mental handicap. PMID- 3097306 TI - Adverse drugs reactions in geriatric patients in the United States. PMID- 3097305 TI - Zinc and the fetus. PMID- 3097307 TI - An introductory assessment of homeopathy. PMID- 3097309 TI - Health knowledge in Ja'afaru L.E.A. Primary. PMID- 3097308 TI - Community health care in Kenya: what next? PMID- 3097310 TI - Pesticide usage and poisoning in Nigeria. PMID- 3097311 TI - Hidden corners of ethnic medical history. PMID- 3097312 TI - Arterial blood gas composition, consciousness and death in rabbits. AB - Conscious rabbits were exposed to environments with low oxygen and/or high carbon dioxide. The electroencephalogram and arterial blood pressure were recorded. Arterial blood samples were taken sequentially. Rabbits became 'unconscious' at an arterial blood PO2 of 25 +/- 1 mm Hg and PCO2 of 99 +/- 27 mm Hg, when simultaneously the environmental oxygen was decreased and carbon dioxide increased. Brain death occurred at a PO2 of 23 +/- 1 mm Hg and PCO2 of 113 +/- 32 mm Hg. Cerebral perfusion was still adequate. In rabbits, the margin between 'unconsciousness' and 'death' is narrow so far as PO2 is concerned. If these results apply generally, animals culled with muscle relaxants may perceive stress involved until shortly before death. PMID- 3097313 TI - Observations on the pathology of experimental encephalitozoonosis in dogs. AB - Experimental transmission of canine encephalitozoonosis was effected by oral dosing of urine obtained from naturally diseased animals. Per os, intraperitoneal and intravenous routes were used to induce infection with tissue culture-grown Encephalitozoon spores which were initially isolated from the kidney of a dog with terminal disease. The infection was confirmed by a rise in the indirect immunofluorescent antibody titres, the lesions found in infected dogs and isolation of the parasite in tissue culture from an infected and immunosuppressed dog. The experimentally induced disease was invariably subclinical but the histopathological changes were similar although milder than those found in fatal natural disease. The kidney appears to be the target organ and chronic interstitial nephritis develops regularly. PMID- 3097314 TI - Pulmonary function in the horse during anaesthesia: a review. AB - The effect of abnormal body position on cardiovascular and pulmonary function in the awake and anaesthetised horse is reviewed. Parameters such as pulmonary shunt, lung volumes, blood gases and alveolar-arterial oxygen partial pressure differences are discussed. Withholding food for 24 hours and mechanical ventilation may be used to improve blood gas values associated with abnormal recumbency during anaesthesia. During prolonged recovery, horses should be encouraged to adopt sternal recumbency. PMID- 3097316 TI - 9,11-Epoxy-9-homo-14-oxaprosta-5-enoic acid derivatives. Novel inhibitors of fatty acid cyclooxygenase. AB - A novel bicyclic prostaglandin analogue, [1R-[l alpha,2 beta (5Z),3 beta,4 alpha]]-7-[3-[(hexyloxy)methyl]- 7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (1), and cogeners were found to be potent inhibitors of fatty acid cyclooxygenase. Compound 1 was the only stereoisomer out of eight possible structures that was active. Ether 1 was 20 times more potent than indomethacin (IND) in inhibiting arachidonic acid (AA) induced aggregation of human platelet rich plasma. Compound 1 was also more potent than IND in several in vivo assays, AA-induced sudden death in the conscious mouse (2 times) and AA-induced bronchoconstriction in the anesthetized guinea pig (16-45 times). PMID- 3097315 TI - Comparative antiaggregatory activity in human platelets of a benzopyranone aci reductone, clofibric acid, and a 2,3-dihydrobenzofuran analogue. AB - A synthetic method for the preparation of aci-reductone 6-chloro-3,4-dihydroxy-2H 1-benzopyran-2-one (3) from 5-chlorosalicylate is presented. In human platelets, the benzopyranone derivative 3, clofibric acid (1), and the 2,3-dihydrobenzofuran analogue 4 inhibited aggregation and serotonin secretory responses to adenosine diphosphate (ADP) with a rank order of potency 3 greater than or equal to 4 greater than 1. Only analogues 3 and 4 consistently blocked the aggregatory responses (greater than 50%) to arachidonic acid (AA) and U46619, a thromboxane A2 agonist. Further, the rank order of inhibitory potency against U46619-induced serotonin secretion was 4 greater than 3 greater than 1. Benzopyranone 3 is of interest since it was the most potent inhibitor of thrombin-induced [3H]AA release (3 much greater than 4 = 1) and more potent than 1 or 4 for the blockade of the ADP- or AA-mediated pathway of platelet aggregation. PMID- 3097317 TI - Antiinflammatory and aldose reductase inhibitory activity of some tricyclic arylacetic acids. AB - A number of dibenztropone, dibenzsuberone, dibenzoxepin, and dibenzthiepin acetic acids were synthesized and tested for antiinflammatory/analgesic activity and also for their ability to inhibit rabbit lens aldose reductase (AR). It was found that the structural requirements for antiinflammatory/analgesic activity, believed to be mediated by inhibition of cyclooxygenase, were much more stringent than were those for AR inhibition. For example, the introduction of a hydroxyl group into positions 1, 4, 6, 7, or 8 on dibenzsuberone-2-acetic acid (1a) had relatively little effect on AR inhibition, but caused wide variations in antiinflammatory/analgesic activity. PMID- 3097318 TI - Synthesis and biological evaluation of irreversible inhibitors of aldose reductase. AB - 5-Isothiocyanatoalrestatin (1b) and 5-azidoalrestatin (1c) were prepared synthetically and examined as potential affinity and photoaffinity inhibitors of rat lens aldose reductase. Both compound 1b and 1c under appropriate conditions at 10(-4) M produced a 70% irreversible inactivation of aldose reductase within 1 min. The enzyme could, in part, be protected by preincubation with sorbinil 2, a known potent inhibitor of aldose reductase. PMID- 3097319 TI - A theoretical study of the binding of polychlorinated biphenyls (PCBs), dibenzodioxins, and dibenzofuran to human plasma prealbumin. AB - Binding energies to human plasma prealbumin using the energy minimization program AMBER are found for a series of polychlorinated biphenyls, dibenzodioxins, and dibenzofuran. Corrections for solvation free energies of the chlorinated analogues lead to estimates of the differential free energies of complex formation. These are compared in a number of cases to known experimental log (KPCB/Kref) values. The theory correctly separates strong, intermediate, and nonbinders. On the basis of calculations, 2,3,7,8-tetrachlorodibenzodioxin and 2,3,7,8-tetrachlorodibenzofuran are predicted to be strong binders, 3,3',5,5' tetrachlorodiphenoquinone is predicted to be a weak binder, and octachlorodibenzodioxin is predicted to not bind at all. This theoretical model for prealbumin interactions may be of use in estimating the toxic potential of PCBs and related halogenated aromatic hydrocarbons of environmental importance. PMID- 3097320 TI - Visualization of biological specimens by cryoHVEM. AB - This article describes the operation and the characteristics of cryoHVEM imaging of biological specimens using a top-entry cryostage. The procedure for inserting frozen specimens into the microscope column is also presented. Whole mounts were observed under optimal imaging conditions by combining: fixation by fast freezing for structure preservation without exposure to chemicals, observation in the hydrated (frozen) state or in the dried state without exposure to the atmosphere after the initial fixation by freezing, and ultrastructural visualization with the key imaging factors of resolution, penetration and beam-induced damage at their best by high-voltage electron microscopy. PMID- 3097321 TI - Sequence conservation around the 5' ends of the larval serum protein 1 genes of Drosophila melanogaster. AB - We have determined the nucleotide sequence at the 5' ends of the genes for the alpha, beta and gamma polypeptides of larval serum protein 1 (LSP1) of Drosophila melanogaster. In their upstream regions, the three genes share homology around the TATA boxes. There is also a homologous region of about 20 nucleotides at positions 200, 216 and 377 upstream from the alpha, beta and gamma genes, respectively. Another 18-nucleotide homology occurs between a sequence 111 nucleotides upstream from the alpha gene and 130 nucleotides upstream of the beta gene. This contains a seven-nucleotide match with a sequence 180 nucleotides upstream from the gamma gene. The sequences corresponding to the 5' non translated regions of the RNA show two regions of strong homology: one being within the first 20 nucleotides at the very 5' end of the RNA, and the other being between nucleotides 27 and 52 of the three transcripts. The first AUG codon to precede a long open reading frame is found at nucleotides 89, 86 and 83 downstream from the 5' end of the alpha, beta and gamma RNAs, respectively. An extremely conserved nucleotide sequence with an exact homology of 66 nucleotides between the alpha and beta genes, and sharing 27 nucleotides with the gamma gene, is contained within this long open reading frame in the first exon. Conceptual translation of the long open reading frame shows that the hydrophobic nature of the first 20 amino acids of the three polypeptides has been conserved whereas the exact sequence has not. This suggests that the N termini contain signal sequences required for secretion of the protein into the haemolymph. The three genes have intervening sequences ranging from 65 to 68 nucleotides in length at comparable locations close to the 5' end of the genes. PMID- 3097322 TI - Expression of the prokaryotic gene for chloramphenicol acetyl transferase in Drosophila under the control of larval serum protein 1 gene promoters. AB - We have linked the protein coding region of the prokaryotic gene for chloramphenicol acetyl transferase (CAT) to the promoter region of the Drosophila genes for larval serum protein 1 (LSP1). These regions consist of 1.65 X 10(3) and 2.25 X 10(3) base long DNA segments upstream from the LSP1 alpha and beta genes, respectively. The hybrid genes have been inserted into a P-element transformation vector and the constructs introduced into cultured Drosophila Kc cells by calcium phosphate-mediated transfection, or into the germ-lines of flies by P-element-mediated transformation. CAT expression occurs in approximately 1% of the cultured cells following transfection and the accumulation of protein is maximal three to four days after transfection; and it is dependent upon the presence of the LSP1 sequences. We have also obtained several lines of transformed flies that carry the LSP1-CAT genes in their germ-line. The onset of synthesis of functional chloramphenicol acetyl transferase in these organisms occurs in the late third larval instar, rising to a maximum at puparium formation. We continue to detect CAT until the first few hours of adulthood. Assays of CAT activity in the homogenates of dissected tissues indicated that the genes are only expressed in the fat body, as are the endogenous LSP1 genes. We have confirmed this tissue-specific localization of CAT in indirect immunofluorescence using an anti-CAT monoclonal antibody. Northern blots indicate that CAT transcripts are found only in the fat body but their abundance is an order of magnitude lower than endogenous LSP1 transcripts. Primer extension experiments show that transcription of the hybrid genes is initiated at the same nucleotide as the endogenous LSP1 genes. Taken together these data indicate that the 1.65 X 10(3) and 2.25 X 10(3) base segments of DNA upstream from the LSP1 alpha and LSP1 beta genes contain cis-acting regulatory elements necessary for correct tissue and temporal specificity of LSP1 gene expression. PMID- 3097324 TI - Crystallization and preliminary data of Indian buffalo erythrocyte carbonic anhydrase. AB - The most abundant anhydrase isoenzyme from the erythrocyte of Indian buffalo has been purified using affinity gel and DEAE-cellulose ion-exchange columns and single crystals suitable for X-ray diffraction studies have been obtained. The unit cell dimensions are a = 46.8 A, b = 104.5 A, c = 60.4 A, beta = 91.2 degrees and the space group is P2(1), with two molecules per asymmetric unit. PMID- 3097323 TI - Structure of the Eip28/29 gene, an ecdysone-inducible gene from Drosophila. AB - The EIPs 28 and 29 are a family of polypeptides identified originally by their ecdysone inducibility in Drosophila cell lines. At least two family members, 28III and 29III, appear to be primary translation products. Here we describe a unique Eip28/29 gene that must encode both primary products. The Eip28/29 gene is unique because the cloned genomic DNA hybridizes to both EIP 28 and 29 messenger RNAs under stringent conditions, but does not anneal detectably to other genomic sequences even under mild conditions. Furthermore the diverse products of this gene are not alleles because flies homozygous for the chromosomal region (71CD) containing the Eip28/29 gene produce mRNAs that translate to yield all the EIPs 28 and 29. We report here the sequence of a 2855-nucleotide region encompassing the Eip28/29 gene. By comparisons with complementary DNA sequences and by nuclease protection experiments we have derived a complete structure for the Eip28/29 transcription unit. The primary transcript is 2146 nucleotides long and is processed by the removal of three introns to yield the predominant mature transcript in tissue culture cells (979 nucleotides). This transcript probably corresponds to the 28III mRNA. Neither the start of the transcription unit nor the structure of the predominant transcript is affected by the hormone ecdysone. The genomic sequence reveals a series of heptanucleotide and octanucleotide repeats of unknown function that fall at about 50-nucleotide intervals within the first 150 nucleotides upstream from the transcription unit. In addition this sequence, when combined with previously published data, suggests that the consensus cap site sequence in Drosophila may be extended to include 13 nucleotides centered on the heptanucleotide core previously recognized by Snyder et al. (1982). PMID- 3097325 TI - The Saccharomyces cerevisiae ADE5,7 protein is homologous to overlapping Drosophila melanogaster Gart polypeptides. AB - The Drosophila melanogaster Gart locus encodes two polypeptides specified by overlapping alternative transcripts. One transcript encodes only glycinamide ribotide synthetase (GARSase) on a 45,000 Mr polypeptide, while the other encodes GARSase aminoimidazole ribotide synthetase (AIRSase), and glycinamide ribotide transformylase (GARTase) on a 145,000 Mr polypeptide. In Saccharomyces cerevisiae, glycinamide ribotide synthetase and aminoimidazole ribotide synthetase are encoded at the ADE5,7 locus. Here I report the cloning, sequencing, and determination of the transcriptional organization of the yeast ADE5,7 gene. There is sufficient homology to align the predicted 802 amino acid ADE5,7 polypeptide with its Drosophila counterpart. These results, together with the sequence of the S. cerevisiae ADE8 gene encoding glycinamide ribotide transformylase, show that the entire Drosophila large polypeptide can be accounted for by the three enzymatic activities. A novel finding is that successive Drosophila domains are each homologous to the aminoimidazole ribotide synthetase portion of the yeast ADE5,7 gene, such that regions of homology with yeast aminoimidazole ribotide synthetase alternate from one of the Drosophila repeats to the other. Such a relationship suggests that the two Drosophila aminoimidazole ribotide synthetase domains together participate in catalysis. This model is consistent with a 20-year-old explanation of complex interallelic complementation such as that characterizing the gene segment encoding yeast aminoimidazole ribotide synthetase. PMID- 3097326 TI - Organization and evolution of variable region genes of the human immunoglobulin heavy chain. AB - We have isolated 23 different cosmid clones of the heavy-chain variable region genes (VH) of human immunoglobulin. These clones encompass about 1000 X 10(3) base-pairs of DNA containing 61 VH genes. Characterization of the 23 clones by Southern blot hybridization showed that VH genes belonging to different families were physically linked in many regions. Cluster 71, which was analyzed in detail, comprised seven VH segments arranged in the same orientation with different intervals. This clone contained internal homology regions, each carrying two VH segments of different families. Comparison of the nucleotide sequences of VH segments within each family showed that profiles of accumulation of mutations in framework (FR) and complementarity-determining (CDR) regions were different. CDR had more mutations at amino-acid-substituting positions than at silent positions, whereas FR had the reverse distribution of mutations. Five out of seven VH segments of this cluster were pseudogenes containing various mutations. VH pseudogenes were classified into two distinct groups; one with a few replacement mutations (conserved pseudogenes), and the other with rather extensive mutations (diverged pseudogenes). The possibility that conserved pseudogenes serve as a reservoir of VH segments is discussed. PMID- 3097327 TI - Phosphocholine binding immunoglobulin Fab McPC603. An X-ray diffraction study at 2.7 A. AB - The crystal structure of the Fab of McPC603, a phosphocholine-binding mouse myeloma protein, has been refined at 2.7 A resolution by a combination of restrained least-squares refinement and molecular modeling. The overall structure remains as previously reported, with an elbow bend angle between the variable and constant modules of 133 degrees. Some adjustments have been made in the structure of the loops as a result of the refinement. The hypervariable loops are all visible in the electron density map with the exception of three residues in the first hypervariable loop of the light chain. A sulfate ion occupies the site of binding of the phosphate moiety of phosphocholine. PMID- 3097329 TI - Electromechanical effects of A23187 on guinea-pig ventricular muscle: a dual action of A23187. AB - The effects of A23187 on electromechanical activity of guinea-pig papillary muscles were examined by microelectrode techniques. A23187 (10(-6) M) caused a marked positive inotropic effect (868% of control) on preparations driven at 0.2 Hz. This inotropic effect was accompanied by a significant prolongation of the action potential duration at an early repolarization phase (APD 10), but not at a late repolarization phase (APD 30 and APD 80). Other parameters of action potential were unaffected. In the presence of nifedipine (10(-6) M), Ca2+ channel blocker, A23187 still increased the contractile force (495% of control) but had no effect on APD 10. On the other hand, APD 30 and APD 80 were significantly shortened. In the presence of ryanodine (2 X 10(-6) M), an inhibitor of internal Ca2+ release, A23187 was also able to cause the positive inotropic effect (389% of control). This inotropic effect was accompanied by a prolonged APD 10. These electrical and mechanical effects of A23187 were completely blocked by the combined treatment with nifedipine and ryanodine, suggesting that A23187 has a dual action. In papillary muscles depolarized by 26 mM [K+]0, A23187 augmented the slow action potential. In voltage clamp experiments using a single sucrose gap method, A23187 caused a marked increase in the slow inward current and the outward current. The effects of A23187 were not antagonized by a beta adrenoceptor and a histamine (H2) receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097328 TI - Micrococcal nuclease as a DNA structural probe: its recognition sequences, their genomic distribution and correlation with DNA structure determinants. AB - We have analyzed micrococcal nuclease (MNase) DNA cleavage patterns at the sequence level by examining 2.3 X 10(3) base-pairs of data derived from the Drosophila melanogaster 44D larval cuticle locus. Within this region, MNase preferentially cleaved 140 sites. Clusters of these sites appear to generate the preferential MNase eukaryotic DNA cleavage sites seen on agarose gels at roughly 100 to 300 base-pair intervals. These clusters of preferential cleavage sites rarely occur within gene coding regions. The analysis revealed that duplex DNA sequences preferentially cleaved by MNase are generally determined by a single strand sequence: d(A-T)n, where n greater than or equal to 1, flanked by a 5' dC or dG. Cleavage of the other strand is generally staggered 5' by several nucleotides and occurs even if such sequences are absent on that strand. An empirical predictive DNA cleavage model derived from a statistical analysis of the sequence level data was applied to seven eukaryotic gene loci of known sequence. The predicted patterns were in good general agreement with the previously observed eukaryotic gene/spacer cleavage pattern. Statistical analysis also revealed that sites of predicted preferential DNA cleavage occur less frequently in protein coding regions than for randomized sequences of the same length and nucleotide content. Comparison of the MNase cleavage patterns to the sequence-dependent pattern of binding energies between duplex DNA strands indicates that MNase preferentially cleaves sequences with low helix stability. PMID- 3097330 TI - Enhanced prostaglandin synthesis due to phospholipid breakdown in ischemic reperfused myocardium. Control of its production by a phospholipase inhibitor or free radical scavengers. AB - The effects of the inhibition of phospholipid degradation and superoxide radical generation on prostaglandin synthesis associated with myocardial ischemia and reperfusion were studied in the isolated, in-situ pig heart model subjected to 60 mins of regional ischemia and a further 60 mins of hypothermic potassium cardioplegic arrest, followed by 60 mins of reperfusion. Myocardial biopsies were taken from the ischemic and non-ischemic regions of the myocardium for measurement of phospholipids, and samples of the perfusate were drawn for estimation of the end-products of arachidonic acid metabolism, 6-keto prostaglandin-F1 alpha and thromboxane B2. A significant amount of 6-keto prostaglandin F1 alpha and thromboxane B2 appeared during reperfusion, corresponding with the loss of membrane phospholipids in control animals. Mepacrine, a phospholipase inhibitor, protected the depletion of membrane phospholipids and inhibited the products of arachidonate metabolism. Superoxide dismutase (SOD) and catalase, on the other hand, enhanced the formation of 6-keto prostaglandin F1 alpha and thromboxane B2. The effects of both mepacrine and the free radical scavengers were pronounced during the reperfusion phase when the most significant depletion in membrane phospholipids occurred. These results suggest that the arachidonate cascade is activated during reperfusion of ischemic myocardium as a consequence of phospholipid breakdown, and this activation can be attenuated by inhibiting phospholipases or enhanced by scavenging oxygen-free radicals generated during reperfusion. PMID- 3097331 TI - Metabolic recovery following temporary regional myocardial ischemia in the rat. AB - The restoration of the cardiac ATP content after an ischemic insult takes a long period of time. Ribose, via stimulation of adenine nucleotide biosynthesis, accelerated the replenishment of the adenine nucleotide pool in the heart, in the kidney, however, it had no effect. In the myocardium, the ribose-mediated restoration of the adenine nucleotide content was dependent on the duration of the previous ischemic period and was not influenced by the beta-receptor blocker atenolol. PMID- 3097332 TI - Carbon dioxide laser myomectomy. AB - A technique for carbon dioxide (CO(2)) laser myomectomy was used in 32 patients from 1981 to 1984; this technique prevents adhesions and blood loss. To assess the effectiveness of this technique, blood loss in the 32 patients was compared with a group of 10 patients who underwent conventional myomectomy. The initial findings indicated that the CO(2) laser is a propitious surgical instrument for myomectomy and that its use yields less blood loss. PMID- 3097333 TI - Cost effectiveness of the antibiotic removal device for processing blood cultures. AB - The antimicrobial removal device (ARD) blood culture system has been reported to increase the sensitivity of isolation of pathogenic microorganisms in bacteremic patients who are already on antibiotics. To determine the usefulness of this system to the clinician for the diagnosis of bacteremia and to determine the additional cost incurred by the use of the system, the microbiological results at two hospitals over a period of two years were compared. A total of 25,124 standard blood cultures (SBC) were performed with a positive culture rate of 10.7 percent. Of the 858 specimens processed by ARD alone, 68 (7.9 percent) were positive. There were a total of 2,657 specimens from 910 patients that were processed simultaneously using both systems. Both ARD and SBC were negative in 2,249 specimens, and 290 blood cultures from 107 patients grew the same organism using both systems. Thirty-one specimens from 12 patients grew pathogenic bacteria from ARD bottles; in each the SBC culture was negative. However, in 21 patients (44 specimens) bacteremia was detected only in SBC with negative cultures from ARD bottles.Thus, in the vast majority of the cases, SBC alone was sufficient to detect bacteremia, even in the patient with recent or concomitant antibiotic therapy. The total processing cost was calculated for the cases in which SBC and ARD were performed simultaneously and was found to be $6,588 for SBC and $15,005 for ARD. The comparative cost per bacteremic patient detected by the two methods was $46.40 for SBC and $555.75 for ARD. PMID- 3097334 TI - The surface charge of Trypanosoma cruzi: analysis using cell electrophoresis, lectins and ultrastructural cytochemistry. AB - The surface charge of epimastigote and trypomastigote forms of Trypanosoma cruzi was analysed by three approaches: a) visualization by electron microscopy of the binding of cationic particles (cationized ferritin at pH 7.2 and colloidal iron hydroxyde at pH 1.8) to the parasite's surface, b) visualization of the binding of fluorescein-labeled lectins (PNA and LPA) to the parasite's surface, and c) by cell electrophoresis. In all cases control, trypsin and neuraminidase-treated cells were analysed. The results obtained indicate that sialic acid residues located on the parasite's surface are responsible for the binding of cationic particles to it and the major component responsible for the net negative surface charge presented by T. cruzi. Phosphate groups, associated to phospholipids, also contribute to the negative surface charge. The effect of previous incubation of the parasites in the presence of lectins (ConA, WGA, PNA, RCA and LPA) on their surface charge was also analysed by cell electrophoresis. PMID- 3097335 TI - Portal fibrosis: intrahepatic portal vein pathology in chronic human schistosomiasis mansoni. AB - Thirty five cases of severe late chronic human schistosomiasis were studied. The attention was given to the portal vascular lesions. Four stages from isolated endothelial involvement to entire portal vein wall disorganization were observed. Ultrastructural evidence of smooth muscle cell dedifferentiation is noted with loss of well defined limits between periportal connective tissue and venous vascular wall. The synergistic action of hypertension, subendothelial transudation of serum and proliferation of vascular connective tissue cell lines, are considered to explain the self perpetuating character of portal fibrosis in chronic human schistosomiasis. PMID- 3097336 TI - Purified scrapie prions resist inactivation by UV irradiation. AB - The development of effective purification protocols has permitted evaluation of the resistance of isolated scrapie prions to inactivation by UV irradiation at 254 nm. Prions were irradiated on ice with doses of UV light ranging up to 120,000 J/m2. UV dosimetry experiments, performed with Saccharomyces cerevisiae plasmid DNA or eucaryotic cells, indicated that under these experimental conditions an incident UV dose of 10 J/m2 formed 2 thymine dimers per 5.1 X 10(6) daltons of eucaryotic cell DNA. The D37 values for scrapie prions ranged from 17,000 to 22,000 J/m2; D37 values were also determined for virus, viroid, and enzyme controls. The number of pyrimidine dimers formed was correlated with the D37 values obtained for irradiated prions and target nucleic acids. The D37 value for bacteriophage M13, 6.5 J/m2, occurred at a dose that would form 0.56 dimers per target genome; the D37 for potato spindle tuber viroid, 4,800 J/m2, occurred at a dose that would form about 24 dimers per target viroid. The D37 value for an EcoRI restriction site, a target of 12 bases, occurred at a dose that would correspond to the formation of 0.89 thymine dimers per target site. The D37 value for prions occurred at a dose that would form 1 dimer in every 4 bases of single stranded target nucleic acid. If the putative scrapie nucleic acid were double stranded and readily repairable after UV damage, then the prion D37 value could reflect a nucleic acid molecule of 30 to 45 base pairs. While the D37 value for prions fell within the range of pure protein targets, our experiments cannot eliminate the possibility that a prion contains a small, highly protected nucleic acid molecule. PMID- 3097337 TI - Disseminated sporotrichosis in a patient with HIV infection after treatment for acquired factor VIII inhibitor. PMID- 3097338 TI - Surreptitious insulin administration in adolescents with insulin-dependent diabetes mellitus. AB - Six adolescents, 12 to 15 years old, with insulin-dependent diabetes mellitus were discovered to be secretively taking extra insulin, not with the intent of improving metabolic control. Large discrepancies between reported and observed insulin requirements were noted. Psychosocial problems antedated the discovery of surreptitious insulin administration in all. Psychological testing and psychiatric evaluation revealed a variety of psychiatric conditions; depression was common. In two patients surreptitious insulin administration was believed to represent suicidal behavior. In others, it appeared to represent symptom substitution when use of other health-threatening behaviors such as recurrent ketoacidosis was made increasingly difficult through appropriate intervention. Surreptitious insulin administration may be one symptom of serious underlying psychiatric dysfunction in adolescents with insulin-dependent diabetes. PMID- 3097339 TI - The comparative cost-effectiveness of statistical decision rules and experienced physicians in pharyngitis management. AB - We examined whether probability-based decisions for streptococcal pharyngitis, using probabilities derived from predictive models along with Tompkins' decision rules, could be more cost-effective than the actual decisions of ten physicians. We retrospectively calculated the probability of a positive throat culture ("disease") for each of 310 patients using four different models based on discriminant analysis (1), a branching algorithm (2), and logistic regression (3 and 4). "Projected decisions" were based on these probabilities and Tompkins' rules. We calculated direct medical and indirect costs per correct action taken (diseased patient-treated or nondiseased patient-not-treated). Two models' projected decisions were more cost-effective than the physicians'. Model 1 primarily would have reduced treatment costs (leaving no diseased patient untreated); model 4 primarily would have reduced throat culture costs (with 15% projected undertreatment). While using statistical decision rules may be cost effective in this setting, their adoption should be consistent with physician and patient priorities. PMID- 3097340 TI - Acute pancreatic inflammation. PMID- 3097341 TI - Rheumatic fever and carditis at the National Institute of Cardio-Vascular Diseases--a follow up study. PMID- 3097342 TI - Serum uric acid in ischemic heart disease. PMID- 3097343 TI - Abnormal hemoglobins 11-Hb (Karachi), an alpha chain abnormality at position 5 Ala----Pro. PMID- 3097344 TI - Incidence of endrin residues in cucumber and its effects on the biological system of rats. PMID- 3097346 TI - Some problems of medical education. PMID- 3097345 TI - Kala-azar in Multan (a case report). PMID- 3097347 TI - A comparison of health and socioeconomic indicators in the townships of Orangi and Karimabad. PMID- 3097348 TI - Dental health of pre-school children in Peshawar in relation to their dietary and oral hygiene habits. PMID- 3097349 TI - Visceral leishmaniasis in children. A new focus in Azad Kashmir. PMID- 3097350 TI - Meningism, pericarditis/myocarditis--unrecognized manifestations of acute porphyria. PMID- 3097351 TI - [Psychological effects of PaCO2 during general anesthesia in elderly patients]. PMID- 3097352 TI - [Efficacy of plasma exchange using cryo removed plasma]. PMID- 3097353 TI - [A case of tsutsugamushi disease with isolation of Rickettsia from peripheral blood and tsutsugamushi disease in Japan]. PMID- 3097355 TI - [The effects of propranolol or nitroglycerin on azygos blood flow in patients with portal hypertension]. PMID- 3097354 TI - [Changes in serum protein in cancer]. PMID- 3097356 TI - [Effect of intratumor mitomycin-C injection on growth of homologously implanted pancreatic cancer in Syrian golden hamster]. PMID- 3097357 TI - [Transcapillary exchange of substances and its measurement]. PMID- 3097358 TI - Transmission of non-A, non-B hepatitis agent to chimpanzees from patients of epidemic hepatitis. AB - Two chimpanzees were inoculated intravenously with acute-phase sera obtained from two patients with epidemic hepatitis. They developed histopathologically confirmed hepatitis. Electron microscopic examination of the liver showed peculiar cytoplasmic tubular structures in the hepatocytes. These ultrastructural findings were similar to those described for the livers of chimpanzees inoculated with the F strain of non-A, non-B hepatitis agent derived from a posttransfusion hepatitis case. The chimpanzee that had recovered from hepatitis caused by the F strain of non-A, non-B hepatitis agent was re-challenged with the serum from one of the patients. The chimpanzee developed neither clinical signs nor histological changes of hepatitis. These results suggested that non-A, non-B hepatitis agent was involved not only in post-transfusion hepatitis but also in epidemic hepatitis. PMID- 3097359 TI - Suppression of lymphocyte responsiveness during acute Rickettsia tsutsugamushi infection in mice. AB - Lymphocytes from Inbred Balb/cyJ mice infected subcutaneously with 10(3) MLD50 of Rickettsia tsutsugamushi Karp strain were unresponsive to rickettsial antigens and phytohemagglutinin in the lymphocyte transformation assay between 11 and 28 days post-infection. There was, however, no correlation between this suppressed responsiveness to rickettsial antigens and the immune capacity to resist a normally lethal ip challenge with the Karp strain. Fourteen days after infection, these mice survived a potentially lethal Karp challenge. Naive recipients of day 14 post-infection mouse splenic lymphocytes also were partially protected against ip challenge. Karp strain-specific anti-rickettsial antibody reached a peak geometric mean titer of 260 during the period of apparent cellular unresponsiveness. However, day 14 post infection mice showed a fourfold decrease of antibody response to a T-dependent antigen, which suggests the presence of T dependent antibody suppression in these mice. PMID- 3097361 TI - [Nursing of patients with deglutition disorders: assistance in parenteral feeding and transition to independent oral feeding]. PMID- 3097360 TI - Segregation of Rh 1(D) and Rh 25(LW) antigens of human Rh blood groups from the Triton-treated fetal erythrocyte membranes. PMID- 3097362 TI - [Nursing of patients with deglutition disorders: prevention of complication- respiratory and nutritional care]. PMID- 3097363 TI - Effects of aldose reductase inhibitor, CT-112, on sugar alcohol accumulation in corneal epithelium of galactose-fed rats. AB - A study was made of inhibitory effects of an aldose reductase inhibitor, CT-112 (5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione) ophthalmic solution, on the accumulation of sugar alcohol (dulcitol) in the corneal epithelium of rats fed on a 50% galactose diet. The effects were correlated with the concentrations of the drug solution. The rats were divided into 6 groups. One group was fed on a regular laboratory chow and was untreated. The other 5 groups were fed on a 50% galactose diet, and 0.1, 0.25, 0.5 or 1.0% CT-112 ophthalmic solution or its vehicle was instilled in both eyes 4 times a day in each of the 5 treated groups. After 2 weeks, the corneal epithelium was scraped off in all rats and its dulcitol content was determined by gas chromatography. CT-112 ophthalmic solution was found to inhibit the accumulation of dulcitol in a dose-dependent manner, except for the 1.0% solution which had an activity comparable to the 0.25% solution. PMID- 3097364 TI - Krypton and argon laser photocoagulation effects in subretinal hemorrhage. AB - Previous studies suggested that krypton laser photocoagulation was more effective in the treatment of macular diseases than argon laser. Furthermore, it could perform photocoagulation more effectively in some lesions with subretinal hemorrhage, because the krypton laser beam was poorly absorbed by hemoglobin. In the present experiment, hemorrhagic retinal detachment was produced in monkey eyes with Q-switched Nd-YAG laser, and 4 weeks later photocoagulation was performed with krypton and argon lasers to compare the differences in the effects of these two lasers. When the subretinal hemorrhage and a heavy coagulation effect was produced in the detached retina, but no coagulation effects were observed in the choroid. Krypton laser beam could go through the hemorrhage and certain coagulation effects were observed in the choroid and the detached retina. It is suggested that krypton laser photocoagulation is more effective in the lesions behind subretinal hemorrhages than photocoagulation with argon laser. PMID- 3097365 TI - Augmented ventilatory activities after airway anaesthesia in humans. AB - The effect of airway anaesthesia by nebulization of 4% lidocaine was studied in 14 healthy human subjects. After airway anaesthesia, a small but significant increase in forced vital capacity and a decrease in expiratory peak flow rate were observed in the pulmonary function test. Blood gas analysis revealed the appreciable depression in arterial oxygen tension. This change was accompanied by the increased alveolar/arterial oxygen tension difference (p less than 0.01) and increased oxygen uptake (p less than 0.01). Resting respiratory rate increased. Although minute ventilation was not changed, mouth occlusion pressure (P0.2) was significantly elevated. Hypercapnic ventilatory responses were augmented, both in terms of VE/PETCO2 and P0.2/PETCO2 slopes. The load compensation ratio, expressed as P0.2 loaded/P0.2 unloaded at rest, was reduced. These results suggested that preferential blockade of vagally mediated pulmonary stretch receptors by airway anaesthesia rather than the irritant receptors may have resulted in augmentation in ventilatory activities. PMID- 3097366 TI - A sporadic case of benign myoclonus epilepsy of adult onset: its clinical aspects and electroencephalographic, polygraphic study. AB - A sporadic case of myoclonus epilepsy of adult onset with a benign course is presented. Its clinical implications were discussed symptomatologically and nosologically. EEG findings consisted of the slowing of basic activity, characteristic polyspike and wave discharges or other paroxysmal patterns and photomyoclonic response (PMR). The PMR was well evoked by flashes of 6-21 Hz and of yellow or red color. Clinical similarities of this case to those of hereditary myoclonus epilepsy without progressive dementia and cerebellar ataxia, and pathognomonic characteristics of electrophysiological findings indicated that the myoclonic epilepsy syndrome might share basic properties, which are state dependent, but independent of underlying neuropathology or heredity. During sleep, paroxysmal discharges with spike(s) significantly decreased in slow-wave sleep and almost recovered in REM sleep. This finding suggests that the brain stem may be responsible for the epileptogeneity in this case. PMID- 3097367 TI - Treatment of amyotrophic lateral sclerosis with thyrotropin-releasing hormone (TRH). AB - Despite the efforts of many workers, the cause and therapy has not been clarified. We carried out the therapeutic trial of thyrotropin releasing hormone (TRH) for amyotrophic lateral sclerosis (ALS) from January, 1979 to January, 1983. There were 16 subjects. The patients were given a low dose (0.5-2 mg) of TRH intravenously or intramusculary. Mild to moderate improvement was found in 9 (56%) of 16 patients. TRH has been reported to have the activating effects on the pyramidal tract, brainstem motor nuclei, and motoneuron in the spinal cord as a neurotransmitter or neuromodulator. We thought such action of TRH to be useful to the therapy of ALS. PMID- 3097368 TI - Isolation of Hammondia hammondi in Japan. PMID- 3097370 TI - Interleukin 2 induced cytotoxicity on renal cell carcinoma. 2. Synergistic effects of interleukin 2 and interferon gamma. PMID- 3097369 TI - Interleukin 2 induced cytotoxicity on renal cell carcinoma. 1. In vitro enhancement of natural killer cell activity. PMID- 3097371 TI - [Comparative efficacy of the long-term use of long-acting nitroglycerin (sustak) and molsidomine after myocardial infarct complicated by heart failure]. AB - Clinical and hemodynamic efficiency of long-term treatment with sustak and molsidomin was assessed in 56 patients following myocardial infarction complicated by circulatory insufficiency within 9 months after discharge from hospital. In spite of the same mechanism of action, long-term treatment with these drugs produces different clinical and hemodynamic effects. The efficiency of prolonged and continuous sustak treatment is shown to decline after 3 months, as reflected in weaker antianginal and hemodynamic effects of the drug. Molsidomin, on the contrary, retains its positive clinical and hemodynamic effects throughout 9 months of use. The long-term use of the peripheral vasodilator molsidomin effectively prevents heart failure in myocardial infarction survivors. PMID- 3097372 TI - Serotonin and the renal blood supply: role of prostaglandins and the 5HT-2 receptor. AB - Serotonin (5HT) has been reported to increase, to decrease, or not to change renal blood flow. We postulated that prostaglandin release in response to 5HT acted as a confusing variable, and tested the hypothesis by comparing infusions of serotonin and angiotensin into one renal artery of 14 anesthetized dogs before and after indomethacin administration. Renal blood flow (Q, by EM flow-meter) responses to 5HT were routinely biphasic, an initial sharp decrease followed by a gradual increase which stabilized well above baseline at three to six minutes. Indomethacin, 1 to 2 mg/kg, did not alter the acute Q decrement induced by 5HT but abolished the increase in Q at three to six minutes (P less than 0.001). Instead, sustained vasoconstriction became apparent. Ketanserin reversed the sustained vasoconstrictor effect of 5HT in indomethacin-treated dogs, leading to striking, serotonin-induced vasodilatation. The latter vasodilatation in turn was inhibited by methysergide. Four independent elements, two promoting vasoconstriction and two vasodilatation, are suggested. One vasodilator response is abolished by prostaglandin synthetase inhibition and the other by methysergide, a complex 5HT receptor blocker. The sustained vasoconstrictor response is blocked by ketanserin, suggesting an action on the 5HT-2 receptor. The initial, transient vasoconstrictor response is resistant to the blockers employed. These complex interactions may account for the variability in reported responses of the renal blood supply to serotonin. PMID- 3097373 TI - Amphotericin B and amphotericin B methylester: effect on brush border membrane permeability. AB - In order to explain the nephrotoxicity of polyene antibiotics such as Amphotericin B (AM), an effect on the tubule membrane permeability has been postulated. However, studies on the action of AM have been complicated by the use of sodium deoxycholate (DOC), a membrane dissociating detergent as a solvent. Recently, a derivative, the methylester aspartate salt of Amphotericin B (AME) has been synthesized, which is highly water soluble in the absence of organic solvents. We have tested the action of AM, DOC, and AME on the sodium permeability of brush border (BBM) vesicles isolated from rat kidney cortex. It was found that both AM and AME increased the 22Na uptake as measured by a rapid filtration technique. However, a large fraction of the AM action was due to the effect of DOC on the BBM sodium permeability. We also investigated the time- and dose-dependent action of AME on 22Na and 3H-D-mannitol efflux from BBM vesicles. After 15 sec of exposure, efflux from 22Na-preloaded vesicles was unchanged in the presence of 1 microgram AME/mg protein compared to control vesicles. With 10, 50, and 100 micrograms AME/mg protein, the efflux increased 16, 25, and 35% respectively; 260 micrograms AME/mg protein did not elicit a further increment in the 22Na efflux. In the same membrane vesicles 3H-D-mannitol efflux did not change. After preincubation of the membranes for 60 min with different concentrations of AME, the 15 sec 22Na efflux increased 26% in the presence of 1 microgram/mg protein AME with no change in the 3H-D-mannitol efflux.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097374 TI - Reversibility of urinary tract abnormalities due to Schistosoma haematobium infection. AB - In view of the controversial results regarding reversibility of urinary tract lesions due to Schistosoma haematobium infection, 103 patients in the People's Republic of Congo were followed up one year after treatment with Praziquantel (40 mg/kg body wt) by means of ultrasonography. The study group consisted mainly of children. Before therapy a total of 113 lesions were detected in the lower urinary tract. These consisted of bladder wall enlargements (N = 53), enlargements of the bladder wall in combination with singular (N = 16) or multiple polyps (N = 30), vesical calcifications (N = 10), and cases with cystitis cystica (N = 4). One year after therapy, a drastic reduction of ova output was observed, and only eight pathological abnormalities of the lower urinary tract were still detectable. Vesical calcifications persisted in four out of ten cases. Urinary tract obstructions of different degrees (N = 42) showed a comparably marked reversibility. It was concluded that, in children, the resolution of bladder lesions induced by urinary schistosomiasis resulted in reversibility of urinary tract obstructions one year after treatment with Praziquantel. PMID- 3097375 TI - Polyunsaturated fatty acids increase fibrinolytic activity of human isolated glomeruli. AB - The release of plasminogen activators (PA) from human isolated glomeruli has been studied by a sensitive radioenzymatic assay using 125I-fibrin coated tubes and plasminogen. The glomerular fibrinolytic activity (GFA) was detectable after 15 minutes of incubation. Then it increased with time, the glomerular protein concentration, and with the plasminogen concentration (P less than 0.001 for all). CaCl2 (1 mM) increased the GFA (9.7 +/- 0.9 versus 4.9 +/- 0.4 micrograms fibrin/mg/30 min, P less than 0.05). The GFA was also enhanced when pH increased. Arachidonic acid (AA, 1 to 20 micrograms/ml) increased the GFA in a saturable manner. Inhibitors of cyclooxygenase (aspirin) or of lipoxygenase (nordihydroguaiaretic acid) did not modify the basal and AA-stimulated GFA. Other polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), eicosatrienoic acid (ETA), eicosatetraynoic acid (ETYA), or dihomo-gamma-linoleic acid (DHL), also stimulated the GFA whereas linoleic acid and oleic acid did not. Polyunsaturated fatty acids also stimulated the fibrinolytic activity of glomerular supernatants. Specific antibodies to t-PA, and to a lesser extent to u PA, decreased this fibrinolytic activity whether or not AA was added. Furthermore, AA and EPA were found to increase the activity of purified u-PA and t-PA. We conclude that human glomeruli release both t-PA and u-PA, and that this release is increased by calcium and alkaline pH. The polyunsaturated fatty acids enhanced the GFA, mainly by a stimulatory effect of PA activity rather than an increased release of PA from glomerular cells. PMID- 3097376 TI - Interferon (IFN)-gamma production by T cell subsets after vaccination with live mumps vaccine. PMID- 3097377 TI - Induction of gamma interferon by mumps virus in lymphocytes from children inoculated with live mumps virus vaccine. PMID- 3097378 TI - [Clinico-economic effectiveness of surgical and therapeutic treatment methods in patients with duodenal ulcer]. PMID- 3097379 TI - [Methods and results of surgical treatment of diverticula of the duodenum]. PMID- 3097380 TI - [Biological valves in biliary tract surgery]. PMID- 3097381 TI - [Urogenital tuberculosis--incidence and clinical laboratory characteristics]. PMID- 3097382 TI - [Intraocular ossification in clinically unsuspected malignant melanoma of the uvea and in phthisis bulbi]. AB - Phthisical eyes of 2 patients revealed clinically unsuspected, partially necrotic and partially vital malignant melanomas of the uvea and extensive intraocular ossification. Both eyes had had recurrent intraocular inflammatory episodes for years before they were enucleated because of pain. Intraocular ossification does not rule out the presence of clinically unsuspected malignant melanoma of the uvea. PMID- 3097383 TI - Human corticotropin-releasing factor (hCRF) is a potent respiratory analeptic. Physiological and clinical aspects. AB - During intravenous corticotropin-releasing factor stimulation tests we observed a deepening of the tidal volume in 35 patients. To investigate this presumed respiratory stimulation we measured respiratory parameters in 12 healthy male volunteers in a single-blind placebo-controlled trial. The intravenous 60-s infusion of 100 micrograms of human corticotropin-releasing factor induced a very potent respiratory stimulation in every subject: respiratory minute volume (mean +/- S.D.) increased by 81% from 6.319 +/- 0.577 to 11.464 +/- 1.264 liters per min (P less than 0.001), whereas there was only a slight rise in the mean respiratory rate from 12.4 +/- 3.0 to 14.7 +/- 2.7 breaths per min (P less than 0.001). Mean tidal volume increased from 531 +/- 105 to 809 +/- 175 ml (P less than 0.001). Mean end-tidal partial pressure of carbon dioxide decreased (P less than 0.001) from 40.3 +/- 1.2 to 33.4 +/- 1.2 mmHg, whereas mean end-tidal partial pressure of oxygen increased (P less than 0.001) from 93.2 +/- 5.4 to 113.5 +/- 5.4 mmHg. After 10 to 20 min both end-tidal carbon dioxide and oxygen partial pressures returned to the baseline values. The placebo had no measurable effects. We conclude that human corticotropin-releasing factor is a potent respiratory stimulant. With 100 micrograms the resting respiratory minute volume increases by 81%. These data point to the possible importance of the corticotropin-releasing factor as a useful adjunct in the management of patients with alveolar hypoventilation. PMID- 3097384 TI - [Mechanism of action of combined administration of glibenclamide and insulin in type II diabetics with secondary failure of oral treatment]. AB - In a double-blind placebo-controlled cross-over study eight type II diabetics (three men, five women), of whom six were at the point of late failure to oral treatment, were given an insulin infusion of 22 U human insulin/patient for 45 min (approximately 7 microU/kg X min); 30 min before infusion either glibenclamide (1 tablet Euglucon N) or placebo was administered. Glucose in venous blood, C-peptide, insulin, and glibenclamide concentrations in the blood plasma were simultaneously determined over a period of 210 min. The monitoring of glucose was handled using a Biostator. The insulin level reached a mean maximum of 400 to 500 microU/ml and was in a behavior of 100 microU/ml for 60 min. The areas under the concentration-time curves (AUCs) were practically identical in the two regimes. The blood glucose fell (in mean) from 260 mg/dl to 135 mg/dl and at the end of the experiment was in the range of 155 mg/dl. The glibenclamide concentrations reached maximal concentrations of 185 ng/ml 90 min after administration. The C-peptide concentrations fell in the placebo phase by more than 40%. In contrast, in the glibenclamide period there was at first a slight rise and later a slight marginal fall (initial, 2.0 ng/ml vs 1.9 ng/ml; 60 min, 1.3 ng/ml vs 1.8 ng/ml; 180 min, 1.2 ng/ml vs 1.8 ng/ml). Values after 90, 120, and 180 min were statistically different. The AUCs (0-180 min) were different (329 ng X min/ml vs 251 ng X min/ml). The inhibition of insulin secretion (measured by C-peptide) caused by exogenous insulin administration is largely abolished by glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097385 TI - [Charting for dollars]. PMID- 3097386 TI - [Experimental research on the process of decomposition of a CO2-CO-H2O-H2-N2 gas mixture in an electrolytic cell with a solid electrolyte]. AB - The experimental investigation was carried out in an electrolytic cell having the form of a short tube and containing a solid electrolyte of the following composition 0.9 ZrO2-0.1 Y2O3. The concentration of the gaseous mixtures investigated [H/C]00 varied in the range 0.22 to 18.0. The cathode polarization of the cell with platinum electrodes was measured as a function of the composition of the gaseous mixture [H/C]00 and oxygen content [O/C + H]0 at the temperatures 800, 900 and 1000 degrees C. The measurements demonstrated that the cell cathode polarization decreased as the water concentration in the starting mixture increased. The dependence of the cell cathode polarization on the oxygen content had minima in a specific range of the values [O/C + H]0. The minimal narrowed and shifted towards lower rations of [O/C + H]0. Simultaneously, the cell cathode polarization decreased as the water content in the starting gaseous mixture increased (ratio of [H/C]00). PMID- 3097387 TI - [Changes in the care of children in pediatric hospitals and their effect on the pediatric nurse's understanding of her role and task]. PMID- 3097388 TI - [Introducing: Action committee Hospitalized Children]. PMID- 3097389 TI - [Considerations on nursing categories in pediatric nursing. Results of multiple action shots]. PMID- 3097390 TI - [The situation in pediatric hospitals and departments following the new hospital financing legislation]. PMID- 3097391 TI - [The psychological care of children as emergency outpatients. Report from Switzerland]. PMID- 3097392 TI - [Care of children before, during and after an endoscopic intervention]. PMID- 3097393 TI - [Children and their illnesses. Service as a development aide in Togo/Western Africa]. PMID- 3097394 TI - [Male and female health nurses, the role of nursing is expanding!]. PMID- 3097395 TI - [Fundamentals and development of tube feeding]. PMID- 3097396 TI - [For and against industrially and home-prepared food for tube feeding]. PMID- 3097397 TI - [Advantages and disadvantages of tube feeding as opposed to parenteral feeding]. PMID- 3097398 TI - [Errors and complications in enteral tube feeding]. PMID- 3097399 TI - [Mechanical aids and technics in enteral tube feeding]. PMID- 3097400 TI - [Catheter jejunostomy]. PMID- 3097401 TI - [Which parameters have to be determined for the control of enteral tube feeding]. PMID- 3097402 TI - [Enteral tube feeding in intensive care]. PMID- 3097403 TI - [Enteral feeding in pediatrics]. PMID- 3097404 TI - [Formulated diets in internal oncology]. PMID- 3097405 TI - [Enteral tube feeding in internal medicine]. PMID- 3097407 TI - [Possibilities with enteral tube feeding in surgery]. PMID- 3097406 TI - [Enteral tube feeding in dental surgery]. PMID- 3097408 TI - [Oral long-term tube feeding]. PMID- 3097409 TI - [Ambulatory enteral tube feeding]. PMID- 3097410 TI - Clinical aspects of congenital adrenal hyperplasia: early diagnosis and prognosis. AB - The neonatal presentation of congenital adrenal hyperplasia is either virilization of females or salt loss in both sexes. Early diagnosis is based on the rapid measurement of plasma 17 alpha-hydroxyprogesterone. Milder forms of congenital adrenal hyperplasia can present later in life with abnormalities of somatic or sexual development. The majority of cases of congenital adrenal hyperplasia are clinically diagnosable in the first 2-3 weeks of life: the need for screening for the remaining missed cases and the late onset types remains to be established. PMID- 3097411 TI - Biochemical aspects of congenital adrenal hyperplasia. AB - The assay of 17 alpha-hydroxyprogesterone in blood spots on filter paper forms the basis of neonatal screening programmes to detect congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The blood concentrations of this hormone in the neonate varies with gestation age (term v preterm), age after birth, time of day and illness. Broad reference ranges for blood spot 17 alpha hydroxyprogesterone concentrations are therefore quoted for healthy term infants and these ranges are not appropriate for the interpretation of values in preterm and sick newborns. There is a risk of a false-negative or of a false-positive diagnosis. Many of the above difficulties may result from variations in assay performance due to changes in the pattern of steroids produced by the adrenal gland which in turn relate to morphological changes in the adrenal cortex at this age. The purpose of this presentation is to define the complex steroid milieu of the newborn human and briefly to review the factors which determine the function of the adrenal gland, since these influence the extent to which an assay for this steroid needs to be evaluated before application to neonatal screening for CAH. The data to be presented derive from the capillary column gas chromatographic analysis (GC) of steroids in urine since this provides the best method to display the overall steroid production of the organism. The GC method has itself been refined so that CAH can now be reliably diagnosed using this method, but the information from this work will also be judged for its relevance to the problems encountered in the neonatal screening for CAH by blood spot analysis. PMID- 3097412 TI - Review of CAH screening programmes and the Scottish experience. PMID- 3097413 TI - Neonatal screening programme for congenital adrenal hyperplasia in a homogeneous Caucasian population. PMID- 3097414 TI - Neonatal screening for congenital adrenal hyperplasia: a pilot study in France. PMID- 3097415 TI - Congenital adrenal hyperplasia in Birmingham: a retrospective analysis (1958 1985). PMID- 3097416 TI - Prevalence of adrenal 21-hydroxylase deficiency in neonates born in the West Midlands: a retrospective study. PMID- 3097417 TI - Human biochemical genetics of enzyme proteins in the new age of molecular genetics. AB - Advances in protein biochemistry and immunology have had a major impact on the biochemical and genetical analysis of human proteins and have had applications in the analysis of the primary defects in metabolic disorders, as well as in cDNA cloning. The development and expansion of somatic cell genetic techniques has complemented conventional population and family study genetic methods. A large number of mammalian proteins undergo complex processing to achieve the synthesis of the biologically active protein. Much of this processing is under genetic control. Elucidation of these complexities requires a combination of biochemical, immunological and genetical approaches to determine the nature of the events involved. PMID- 3097419 TI - Molecular basis of alpha 1-antitrypsin deficiency and its potential therapy by gene transfer. AB - The gene for alpha 1-antitrypsin, a serum anti-protease, has been cloned and sequenced. The underlying mutation in the PiZ allele has been identified as a G to A conversion giving rise to the substitution of glu by lys at position 342. Preparation of specific probes has allowed prenatal diagnosis. Recombinant retroviruses containing the normal human alpha 1-antitrypsin gene have been constructed and used to infect NIH3T3 cells. Analysis of DNA, RNA and protein indicate that successful incorporation of the alpha 1-antitrypsin was achieved and that the gene was capable of being expressed. The feasibility of genetic replacement therapy has been demonstrated and further experiments justified. PMID- 3097420 TI - Direct alteration of a gene in the human genome. AB - Direct alteration of a gene in the human genome requires an understanding of the role of the gene in metabolism. A gene may need to be introduced into a specific tissue or alternatively it may be possible to use accessible tissue such as bone marrow. The level of gene expression required also needs to be known as does the position in the genome into which the gene is to be inserted. Insertion of DNA needs to be of high efficiency and accuracy. Various methods are available including virus, the use of inert adjuvant, microinjection and electroporation. The procedure with the most potential for accuracy is the use of specially designed plasmids. The example of the use of such a plasmid in achieving target modification of the beta-globin gene is given. The method has high accuracy but low efficiency. PMID- 3097418 TI - Human DNA repair defects. AB - A number of human genetic diseases have come to be described as being defective in DNA repair. The minimum criterion on which this assignment is based is hypersensitivity to the clastogenic or lethal action of specific DNA damaging agents. In one disease, xeroderma pigmentosum, the molecular evidence for a defect in DNA repair is unequivocal. This condition then acts as a model for dissecting others. For the other diseases the formal evidence for defects in repair is less secure or even lacking. The evidence for repair in each disease is assembled together with any methods that have been used to support the differential diagnosis or for prenatal diagnosis. Attempts to clone human DNA repair genes are in hand and may provide the necessary evidence to decide if all the putative DNA repair defective diseases are genuine. Neoplastic disease and neurological degeneration together with immune defects are frequent clinical features linking this set of diseases, suggesting that effective DNA repair may be important in many aspects of human health. PMID- 3097421 TI - Blood-brain barrier breakdown by cold injury. Polyamine signals mediate acute stimulation of endocytosis, vesicular transport, and microvillus formation in rat cerebral capillaries. AB - Polyamines have been previously implicated in the mediation of blood-brain barrier breakdown induced by cryogenic injury (H Koenig, AD Goldstone, CY Lu, Biochem Biophys Res Commun 116:1039, 1983). We studied acute (less than 5 minute) changes in capillary ultrastructure, microvascular permeability, and the levels of polyamines and their rate regulating synthetic enzyme ornithine decarboxylase (ODC) in rat cerebral cortex after focal cold injury. Microvascular permeability was measured by relative transport of intravenously administered fluorescein. Capillary ultrastructure was studied by quantitative stereology and morphometry after intravenous administration of horseradish peroxidase. Focal cold injury induced a 2.5-, 3.8-, 1.7-, and 1.4-fold increase in the levels of ODC, putrescine, spermidine and spermine, and a 46-fold increase in fluorescein uptake in perilesional cortex. Few capillaries in control cortex contained endocytic pits or horseradish peroxidase-positive vesicles, whereas most capillaries near lesions showed these structures. Cryoinjury induced a 5-fold increase in the relative volume of microvilli and horseradish peroxidase vesicles, a 2.3-fold increase in area of luminal endocytic pits, and a 6.3-fold increase in area of abluminal exocytic pits. The ODC inhibitor alpha-difluoromethylornithine blocked the cryoinjury-induced changes in ODC, polyamines, fluorescein uptake, and capillary ultrastructure. Putrescine negated the effect of alpha difluoromethylornithine or capillary ultrastructure, and was previously shown to nullify the alpha-difluoromethylornithine effects on polyamines and fluorescein permeability (cited above). These data link rapid changes in ODC and polyamines to blood-brain barrier breakdown, and suggest that the abnormal permeability is associated with an acute, polyamine-mediated stimulation of microvillus formation, endocytosis, and vesicular transport in capillary endothelium. PMID- 3097422 TI - Partial splenectomy with the CO2 laser: an alternative technique. AB - Because total splenectomy has been shown to affect immunocompetence in children, partial splenectomy is advocated as an alternative to total splenectomy in traumatic injury as well as in treatment of benign cysts. Present techniques include elaborate hemostatic techniques and extensive suture repair which has led to the development of massive abdominal adhesions. We have investigated CO2 laser sealing of splenic wounds to obviate the need for extensive repair and to minimize intraabdominal reaction. Five dogs underwent partial splenectomy with a scalpel. Hemostasis was obtained with CO2 laser coagulation; a defocused laser beam at 8 W (power density 30-50 W/cm2). After 3 weeks, the laser sealed splenic tissue was amputated and, on this occasion, hemostasis was obtained using a standard suture technique of Teflon pledget-bolstered chromic sutures. Three weeks later the dogs were explored and the sutured splenic tissue was removed. Gross findings on the first exploration demonstrated no signs of hemorrhage and minimal adhesions of the laser sealed spleens. In contrast, exploration after suture repair revealed dense adhesions containing the spleen, omentum, mesentery, and small and large bowel. Microscopic examination of the laser sealed spleen showed a zone of injury only 2-3-mm thick. Excellent hemostasis of the cut surface of the spleen can be accomplished using the CO2 laser. In addition, the minimal depth of injury and the absence of foreign material in the peritoneal cavity make this an attractive alternative to conventional methods. PMID- 3097423 TI - Calcium-retarding agent (T6) for porcine valves. PMID- 3097424 TI - Pulmonary aspergilloma. Results of surgical treatment. AB - Between 1953 and 1984, 53 patients (40 male and 13 female) underwent thoracotomy for treatment of pulmonary aspergilloma. The median age was 58 years (range 4 to 86 years). Either underlying lung disease or immunologic risk factors were present in 49 patients (92%). Twenty-one patients (31%) had simple aspergilloma and 32 (47%) had complex aspergilloma. The most common indication for operation was an indeterminate mass, hemoptysis, or severe cough. Lobectomy, wedge excision, and pneumonectomy were the most frequent operations. Complications occurred in 78% of patients with complex aspergilloma and in 33% of patients with simple aspergilloma (p = 0.002). Operative mortality was 5% (one death) in patients with simple aspergilloma and 34% (11 deaths) in patients with complex aspergilloma (p = 0.01). Cause of death was respiratory failure in four patients, underlying pulmonary disease in three, aspergillosis in two, and other conditions in three. At follow-up, 84% of operative survivors with simple aspergilloma were alive and well compared with 43% of those with complex aspergilloma. Although operative mortality in patients with complex aspergilloma was high, 67% of the survivors had a good long-term result in terms of absence of symptoms, but they frequently died of underlying disease. In contrast, operation in patients with simple aspergilloma was done with low risk, and approximately 90% of survivors had a good late result. Late appearance of contralateral disease did occur and argues for rigorous postoperative surveillance. PMID- 3097425 TI - Cytokines in radioprotection. Comparison of the radioprotective effects of IL-1 to IL-2, GM-CSF and IFN gamma. AB - Immunomodulatory agents are radioprotective when administered to animals prior to irradiation. The mechanisms for this radioprotection have as yet not been determined, but may involve endogenously released cytokines. We have recently demonstrated that murine IL-1 is radioprotective in mice (Neta et al. J. Immunol., 136, 2483, 1986). In this study we have further explored this effect and investigated whether the radioprotective effect of IL-1 is mediated by other cytokines. Optimal radioprotection with IL-1 was obtained with administration 20 hr prior to irradiation and was greatly reduced with administration 45 or 4 hr before or 1 hr after irradiation with 950 cGy, an LD100/30 dose. The dose reduction factor (DRF) measured by LD50/30 was 1.25 for C57B1/6 mice. The presence of a lag period in IL-1 induced radioprotection suggests that the effect of IL-1 may be indirect. The hypothesis that IL-1 may act by inducing the release of other cytokines was tested in part by two approaches: Assays for circulating IFN and CSF. High titers of CSF were present at 3 and 6 hrs and declined at 24 hrs after administration of 0.1 microgram of IL-1, a dose radioprotective in mice. Assays for IFN in the same sera were negative. Direct administration of recombinant IFN-gamma, GM-CSF, or IL-2 prior to LD100/30 irradiation. Using a wide range of doses of these cytokines delivered 20 or 3 hr prior to irradiation, no significant radioprotective effect was observed. PMID- 3097426 TI - The regulation of human interferon-gamma production by interleukins 1 and 2. PMID- 3097427 TI - Antimicrobial and antitumor assays for the measurement of non-IFN-gamma human MAF. PMID- 3097428 TI - Interleukin 2 binding capacity of human mononuclear leukocytes. AB - Interleukin 2 (IL-2) receptors which are expressed in T-lymphocytes after antigenic or mitogenic stimulation have been measured with either 3H- or 125J labelled IL-2 or with receptor antibodies (e.g. anti-Tac). We have developed a new method which allows the determination of endogenously bound IL-2, or of the IL-2 binding capacity, respectively. The method utilizes incubation of target cells with human natural highly purified IL-2. Total bound IL-2 is determined by a conventional 3H-thymidine incorporation assay. An additional step, differential dissociation, eliminates low affinity bound IL-2 so that the remaining high affinity bound IL-2 can be determined. In PHA stimulated mononuclear cells we have found that high affinity binding sites appear after one day at high concentration and disappear gradually after more than ten days of culture. Low affinity binding sites appeared first on day 2, but showed then similar kinetics. IL-2 binding capacity closely correlated with the ability of the cells to respond to exogenous highly purified human IL-2. Our results demonstrate that in vitro in healthy blood donors the expression of IL-2 binding sites is necessary to render the cells responsive to IL-2 and to induce polyclonal expansion. Pharmacological doses of hydrocortisone abolishes both, IL-2 binding and IL-2 response. PMID- 3097429 TI - Induction of lymphokine synthesis in peripheral blood mononuclear cells with phorbol ester and calcium ionophore allows precise measurement of individual variations in capacity to produce IL 2. AB - Absolute capacity for IL2 production by human peripheral blood mononuclear cells (PBMC) was studied using 12-O-tetradecanoylphorbol 13-acetate (TPA) and calcium ionophore A23187, which act synergistically, to induce lymphokine synthesis. Culture parameters were optimized for the TPA/A23187 stimulation such that maximal IL2 titers were produced with a high degree of reproducibility. Thus, using a synthetic medium, TPA/A23187 at 20/50ng/ml respectively, and a cell concentration of 2.5 X 10(6)/ml, IL2 titers in the cultures increased linearly over a period of 96h, reaching values at least 15-fold higher than with lectin stimulation. This allowed for determinations of IL2 synthetic capacity in individual blood samples. Large fluctuations in normal IL2 production (range 1775 10654 BRMP U/ml at 48h) were observed among 23 normal persons. A statistically significant lower IL2 productive capacity was observed in the age group above 40 as compared to those under 40. The lower rates of IL2 synthesis in a group of patients with Hodgkin's disease was seen only among those who had undergone immunosuppressive therapy; newly diagnosed cases fell within the normal range. PMID- 3097430 TI - Functional adaptations of the bronchial circulation. PMID- 3097431 TI - Acute effects of oleic acid-induced lung injury in baboons. PMID- 3097432 TI - Bronchoconstriction and apnea induced by cigarette smoke: nicotine dose dependence. PMID- 3097433 TI - [Resistance of Neisseria gonorrhoeae to antibiotics]. PMID- 3097434 TI - [Splenectomy: the first step in the treatment of pure erythrocytic aplasia?]. PMID- 3097435 TI - [Technical aids for a better quality of life in prolonged parenteral nutrition]. PMID- 3097436 TI - Nonflammable endotracheal device for CO2 laser ablation of benign laryngeal and proximal tracheal tumors. AB - A Holinger aspirating tube may be utilized as a nonflammable endotracheal device during CO2 laser ablation of benign laryngeal and proximal tracheal tumors. Adequate jet ventilation may be performed through this small diameter (3.0 mm), metallic device while providing an unobstructed view of the surgical lesion. This technique was well-accepted by surgeons during the clinical trials. Because the 3.0 mm outside diameter was significantly smaller than the smallest flexible, uncuffed metal endotracheal tube currently available (6.9 mm), the rigid structure facilitated atraumatic insertion past the surgical lesion. Both the use of this device and the required anesthetic technique are described in three CO2 laser ablative procedures. The authors consider that this device increases safety during this potentially hazardous procedure by eliminating the flammable polyvinyl chloride endotracheal tube and cottonoid packings most frequently used during this procedure. PMID- 3097437 TI - Determination of plasma [18F]-6-fluorodopa during positron emission tomography: elimination and metabolism in carbidopa treated subjects. AB - An investigation of the metabolism of [18F]-6-fluorodopa (FDOPA) given to carbidopa treated subjects for scanning by positron emission tomography (PET) has been carried out by analysis of plasma. Reverse phase ion pair HPLC and alumina extraction were employed to fractionate and identify the [18F]-labelled compounds of plasma over a two hour period. During this time, the plasma levels of both total 18F and FDOPA decreased as a bi-exponential function of time. The rates of 18F, but not FDOPA, elimination were observed to decrease with age. In addition to FDOPA, only one other major peak of radioactivity was resolved by HPLC. Identification of this compound as the O-methylated derivative of FDOPA (MeFDOPA) is based on its shared HPLC elution time with in vitro synthesized O-[methyl-14C] FDOPA. The ratio of the concentration of MeFDOPA to FDOPA (MeFDOPA/FDOPA) in plasma increased linearly with time, and the slope of this linear relationship decreased with the age of the individual. PMID- 3097438 TI - [Clinical study of low-flow anesthesia with isoflurane. II. Respiratory effects of isoflurane in low-flow anesthesia and interaction of isoflurane and muscle relaxants]. PMID- 3097439 TI - Comparison of the cardiac effects of naloxone administration after fentanyl and halothane anesthesia. PMID- 3097441 TI - Chorionic villi sampling. PMID- 3097440 TI - Ethics and patient teaching. PMID- 3097442 TI - Principles of documentation. PMID- 3097444 TI - Back to the theories: another way to view mothers of prematures. PMID- 3097443 TI - Pregnant women with systemic lupus erythematosus. PMID- 3097445 TI - Care of postpartum adolescents. PMID- 3097446 TI - AIDS: the implications for home care. PMID- 3097448 TI - An innovative documentation tool. PMID- 3097447 TI - Ribavirin for treatment of RSV infection. PMID- 3097449 TI - Selecting measurement instruments. PMID- 3097450 TI - [Neutron therapy of head and neck tumors]. AB - The results of therapy of 55 head and neck tumor patients using fast neutrons of the Y-120 cyclotron of the Research Institute of Nuclear Physics, Tomsk Polytechnical Institute, were analyzed. For design of courses of neutron and combined neutron-photon therapy formulas of DMF calculation were used in cases of homogeneous and arrhythmic dose fractionation. The authors presented some data on methods of therapy with fast neutrons, dose fractionation schedules, a focal dose value, and time of treatment. Complete tumor regression was noted in 50-54% of cases using fast neutrons alone or in combination with photon radiation. A high sensitivity to neutron radiation of nonepidermoid carcinomas as compared to epidermoid cancer types was established with relation to tumor morphological structure. PMID- 3097451 TI - [Use of an immunoelectrophoretic apparatus for rapid diagnosis]. AB - Some experimental results obtained by using newly designed sets for express diagnosis are presented. The operation of sets is based on the counterimmunoelectro-osmophoretic method. PMID- 3097452 TI - Lactic acid output of cat gastrocnemius-plantaris during repetitive twitch contractions. AB - Because fatigable, white (FF) muscle fibers have been reported to have a greater glycolytic capacity and a lower oxidative capacity than fatigue-resistant, red (FR and SR) muscle fibers, it is generally supposed that FF muscle fibers produce and therefore release more lactic acid into the blood during contractions than FR and SR muscle fibers. To test this supposition, the net lactic acid output, L, and O2 uptake, VO2, were measured for the cat gastrocnemius-plantaris muscle during repetitive isometric contractions. The results obtained from this low metabolic capacity (FF, FR and SR muscles) were compared to results obtained previously in the high metabolic capacity (FR and SR muscles) of the same muscle group in the dog during similar contractions. Preliminary studies established that 1 twitch X 2 s-1 provided a similar VO2 pattern during the contractions of cat muscle as 4 twitches X s-1 produced in the dog muscle. The decline in VO2 over a 30-min period of contractions was 12 to 18%, as developed tension declined with fatigue. Thus, the contractions of the cat muscles were matched with the dog muscles in terms of the relative aerobic capacity and development of fatigue. During the 1 twitch X 2 s-1 twitches, the VO2 reached 24.4 +/- 1.41 (SE) microliter X g-1 X min-1 at 10 min of contractions. The VO2 declined to 21.3 +/- 2.3 microliter X g-1 X min-1 by 30 min. The VO2 and tension developed changed parallel to each other. The net L reached 0.21 +/- 0.06 mumol X g-1 X min-1 at 10 min and fell to 0.13 +/- 0.05 mumol X g-1 X min by 30 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097453 TI - Acute effects of marihuana smoking on maximal exercise performance. AB - To evaluate the effects of marihuana smoking on exercise performance, 12 healthy young subjects did progressive exercise testing on an ergocycle to exhaustion under two conditions: non-smoking (control) and 10 min after smoking a marihuana cigarette (containing 1.7% of delta-9-tetra-hydro-cannabinol) of 7 mg X kg-1 body weight. Heart rate, arterial blood pressure, minute ventilation (VE), breathing rate (fb), oxygen uptake (VO2), and carbon dioxide output (VCO2) were measured before, during, and for 4 min after the exercise. Tidal volume was calculated from VE X fb-1. The exercise duration was also measured. Forced expiratory volume (FEV1) was measured: before smoking (rest); before exercise (10 min after smoking); and after exercise. Carboxyhemoglobin levels were measured before and 10 min after smoking in four subjects. Marihuana smoking reduced exercise duration (16.1 +/- 4.0 to 15.1 +/- 3.3 min, P less than 0.05). At peak exercise performance, there were no differences in VO2, VCO2, heart rate, and VE between the two experimental conditions. Marihuana induced tachycardia at preexercise (94.3 +/- 13.3 beats X min-1 to 119.0 +/- 18.0, P less than 0.01) that was sustained up to 80% of maximum effort and during the recovery period. After marihuana, VE, VO2 and VCO2 were increased above control from 50% of maximum effort to the end of the test. Marihuana induced a bronchodilation (FEV1 from 4.28 +/- 1.00 to 4.43 +/- 1.031, P less than 0.0) that was still present after exercise. Exercise induced a bronchodilation in the control condition but not in the marihuana smoking condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097454 TI - Necrobiotic xanthogranuloma with paraproteinemia. A review of 22 cases. AB - Cutaneous biopsy specimens from 22 patients showed the distinctive histopathologic pattern of necrobiotic xanthogranuloma within the dermis or subcutaneous tissue (or both). Twenty of the 22 patients had 1 or more serum protein abnormalities, consisting of an IgG monoclonal protein in 16, multiple myeloma in 3, cryoglobulinemia in 3, and an abnormal serum protein electrophoresis in 1. Cutaneous lesions were seen as discrete, slowly developing red nodules and plaques with a xanthomatized hue and a predilection for the face (periorbital region in particular), trunk, and extremities. Ulceration was a notable finding in 10 patients. Histologically, the dermis and lobules of subcutaneous tissue were involved with a granulomatous infiltrate containing bands of hyaline necrobiosis and bizarre foreign body, as well as Touton giant cells. Cholesterol clefts, lymphoid nodules with or without germinal centers, and foci of plasma cells were variable but significant features. Leukocyte monoclonal antibody studies in 6 patients demonstrated helper T cells within the granulomas. Electron microscopy in 3 cases showed lipid vacuoles in macrophages in the dermis and dendritic cells in the epidermis, and study confirmed this entity as a non-X histiocytosis. Pertinent laboratory findings, in addition to the serum protein abnormalities, included elevation of the erythrocyte sedimentation rate, leukopenia with absolute neutropenia, and decreased serum complement levels, as well as decreased levels of C1-esterase inhibitor in some patients. Thirteen of the 22 patients have survived, the mean duration being 9.5 years after the onset of cutaneous disease. While given to only a few patients in the current series, low-dose chemotherapy seems to induce a favorable response in both the cutaneous and the hematologic disease. PMID- 3097455 TI - The interaction of 2 diseases: diabetes mellitus and cystic fibrosis. AB - We have reviewed the hospital records of 24 patients with cystic fibrosis associated diabetes, and 2 groups of CF patients (1 with normal and the other with abnormal oral glucose tolerance tests) who did not develop symptomatic fasting hyperglycemia, to define the clinical characteristics of the diabetes and to study its effects on the progression of the pulmonary disease, changes in sputum organisms, and mortality. Although maximum blood glucoses ranged from 322 to 1160 mg/dl with a median of 579 mg/dl, only 1 of 24 diabetic patients developed ketoacidosis. This patient developed diabetes 12 years prior to the diagnosis of CF and may have had type 1 diabetes. In contrast, hypoglycemia was frequent and 4 patients were hospitalized with serious neurologic manifestations. Two patients were found to have diabetic retinopathy, 1 with macular edema required laser photocoagulation to improve vision, and the other had multiple microaneurysms. CF-associated diabetes did not influence the deterioration of clinical scores, chest x-ray scores, pulmonary function tests, the number of hospital admissions, the type of organisms found in the sputum, or mortality rates. The development of diabetes in our CF patients was not related to the severity of pulmonary dysfunction, clinical, or chest x-ray scores. Thus, although the development of diabetes is an additional encumbrance upon the already therapeutically burdened existence of a CF patient, it does not appear to affect the course of the disease. Despite the demonstration of diabetic retinopathy in this study, most patients with CF-associated diabetes still do not live long enough to develop microvascular complications from the diabetes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097456 TI - Quantitating genetic and nongenetic factors that determine plasma sex steroid variation in normal male twins. AB - We have observed that familial factors have a decided influence on the plasma content of sex steroids in men both in the general population and in men of families with prostatic cancer. The contribution of genetic and nongenetic familial factors on the variation of plasma sex steroid content and action has now been investigated in 75 pairs of normal male monozygotic (MZ) twins and 88 pairs of dizygotic (DZ) twins. Zygosity was determined by measuring ten blood proteins and enzymes. The mean plasma values for testosterone (T), dihydrotestosterone (DHT), estradiol (E2), estrone (E1), and 3 alpha androstanediol glucuronide (3 alpha-diol G), free T, LH, FSH, SHBG, age, and degree of adiposity were all similar between the groups of twins. Familial factors (P less than 0.01) accounted for 50% or more of the variation in plasma hormone levels in MZ twins (3 alpha-diol G, 84%; T/DHT, 70%; T, 63%; E1, 63%; free T, 61%; E2, 57%; DHT, 56%; LH, 55%; and FSH, 54%) except for SHBG, which was 30%. The familial influence was greater in MZ twins than in DZ twins for all measurements except for SHBG. The heritability of the variation of hormone levels in plasma was determined from the equation: 2[rMZ(intraclass correlation) - rDZ]. Genes regulate 25% to 76% of the total variation of plasma content of the hormones except for DHT (12%) and SHBG (less than 1%). Genetic regulation of tissue DHT formation was suggested by observing a 48% genetic effect on the plasma content of 3 alpha-diol G.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097457 TI - Unchanged nonshivering thermogenic capacity of dystrophic mice. AB - The rate of oxygen consumption measured at 32.5 degrees C of lightly anesthetized 129/ReJ dy/dy mice was greater than that of dy/+ or +/+ control mice. However, the norepinephrine-stimulated rates of oxygen consumption of dystrophic and normal mice were similar. Brown adipose tissue cellularity (DNA content) of dystrophic mice was unchanged, and the tissue protein and succinate dehydrogenase contents were slightly reduced. The mitochondrial concentration of the uncoupling protein, thermogenin, and purine nucleotide binding to mitochondria isolated from brown fat of normal or dystrophic mice, were similar. These results indicate that the nonshivering thermogenic capacity of dystrophic mice is not significantly altered. PMID- 3097458 TI - Steroid and gonadotropin levels in women during the peri-menopausal years. AB - We obtained blood samples from 88 women 45-58 yr old who were having cyclic menses every 1-2 mth (37 women, 133 samples) or were amenorrheic for greater than 3 mth (51 women, 310 samples). Samples were obtained at intervals of 3-4 mth and analyzed for estrogens, androgens and gonadotropins using radioimmunoassay techniques. There was a gradual decline in the concentrations of estrone (E1), estradiol (E2), estrone sulfate (E1SO4) and progesterone (P) as the time from the last menses increased. A relatively stable concentration was reached in 12 mth for E1, E2, and E1SO4 and in 2 mth for P. The concentrations of testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate remained relatively constant as the time from the last menses increased. There was no apparent difference in the mean values of any of these hormones for any time interval from the last menses. The concentrations of both luteinizing hormone (LH) and follicle stimulating (FSH) were noted to increase initially but they appeared to become stable after 12 mth for FSH and after only 6 mth for LH. Using only the measurements made on the initial blood samples obtained in all patients, we found significant correlations between FSH concentrations and the concentrations of E1, E2 and E1SO4 for women who were less than 3 mth from a menses as well as those whose last menses had occurred 3 or more mth previously. The correlations were generally not significant for LH in either groups of women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097459 TI - Amino acid requirements of Eikenella corrodens. AB - The amino acid requirements of asaccharolytic Eikenella corrodens strains were investigated and a minimal amino acid medium was developed. Single amino acid deletions performed in a chemically defined medium indicated that these strains required arginine, cysteine, histidine, lysine, and proline, and partially required tyrosine. These six amino acids plus aspartic acid, glutamic acid, and glycine supported growth of E. corrodens in a medium containing only inorganic salts and vitamins. PMID- 3097460 TI - Utilization of pyrimidines and pyrimidine analogues by fluorescent pseudomonads. AB - The fluorescent pseudomonads Pseudomonas aeruginosa, Pseudomonas aureofaciens and Pseudomonas putida were examined for their ability to utilize pyrimidines and pyrimidine analogues. Both P. aeruginosa and P. aureofaciens grew upon dihydrouracil, dihydrothymine, uridine and cytidine as either a sole nitrogen or carbon source while uracil, thymine and cytosine served only as sole nitrogen sources for both pseudomonads. The only difference between the observed growth of P. aeruginosa and P. aureofaciens on pyrimidines was that deoxycytidine sustained the growth of P. aeruginosa as a nitrogen source. With respect to P. putida, uracil, cytosine and cytidine were found to be nitrogen sources while dihydrothymine, uridine and cytidine served as carbon sources. The fluorescent pseudomonads investigated had fourteen nutritional characteristics which were determined in common for the pyrimidines screened. All the fluorescent pseudomonads were sensitive to a low concentration of 5-fluorouracil. Inhibition by 5-fluorouridine of P. aureofaciens growth was observed at a low concentration while a high concentration of this analogue was required to halt P. putida growth. Neither P. aureofaciens nor P. putida could grow in the presence of a high concentration of 5-fluorocytosine. Only P. aureofaciens growth was noted to be inhibited by a high concentration of 6-azauracil. PMID- 3097461 TI - Microcalorimetric studies on the effects of media and environmental conditions on the growth of bacteria. AB - A study has been made of the effects of media and oxygen tension on the power time (p-t) traces exhibited by cells of Klebsiella aerogenes, Staphylococcus aureus and Pseudomonas aeruginosa. The p-t traces were more complex in shape when the cells were grown in rich nutrient medium than when grown in chemically defined glucose-limited medium. There was less waste heat and more biomass was produced during growth in nutrient broth. The oxygen tension had a profound effect on the shape of the p-t traces, and two strains of S. aureus, which differed in antibiotic susceptibility, exhibited different traces at the same oxygen tension. The thermal yield of the resistant strain was less than that of the sensitive strain. The choice of medium and the level of aeration, rather than the organism, determined the shape of the p-t trace. This has serious consequences for the proposed use of microcalorimetry as a rapid method for bacterial identification. PMID- 3097462 TI - Conjugal transfer of beta-lactamase-producing plasmids of Neisseria gonorrhoeae to Neisseria meningitidis. AB - Twenty clinical isolates of beta-lactamase-producing Neisseria gonorrhoeae from Japanese sources were studied to define their ability to serve as donors for their plasmids in conjugation with Neisseria meningitidis. These twenty strains of N. gonorrhoeae harbored the 4.5-megadalton (Mdal) beta-lactamase-producing plasmids and the 24.5-Mdal conjugative plasmids. We found that only three of twenty N. gonorrhoeae strains showed a detectable conjugation frequency (greater than 10(-5)) with N. meningitidis as the recipient although all strains were capable of mobilizing beta-lactamase-producing plasmids to N. gonorrhoeae and to Escherichia coli. The 4.5-Mdal beta-lactamase-producing plasmid was maintained in N. meningitidis, but the large 24.5-Mdal conjugative plasmid has not been found in N. meningitidis transconjugants. PMID- 3097463 TI - Automated noninvasive determination of mixed venous pCO2. AB - The determination of mixed venous pCO2 is desirable for assessing the metabolic and respiratory status of a patient. A totally automated, laboratory computer controlled noninvasive system has been developed to determine mixed venous pCO2 by an equilibrium rebreathing method or by an exponential compartmental analysis for cases in which equilibrium is not achieved. A gas mixture is charged to a 2 liter anesthesia bag contained in a thermostatically controlled chamber used to maintain the temperature at 37 degrees C. This feature improves upon past rebreathing methods and eliminates water vapor as a variable in gas composition measurement. This bag is connected to a rebreathing circuit controlled by a minicomputer. The subject breathes from a mouthpiece attached to a two-way valve and rebreathes the gas mixture for a period of 30 seconds. Inspirate and expirate hoses are placed in the rebreathing bag to ensure a more uniform gas distribution than is generally found in rebreathing systems. Exchange of CO2 takes place between lungs and rebreathing bag, and the concentration of CO2 is continuously monitored by a mass spectrometer. After a period of time, the concentration of CO2 in the rebreathing bag, the alveoli, and the mixed venous blood come into equilibrium, demonstrated by a plateau on the record of CO2 concentration vs. time. Compartmental analysis predicts the mixed venous pCO2 even if an equilibrium is not established. This feature is a significant benefit of this new method, eliminating problems associated with establishing an equilibrium, such as gas mixture volume adjustment, recirculation, and poor ventilation. The predicted value agrees with the equilibrium valve for cases in which equilibrium is reached.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097464 TI - A quantitative assessment of portal film contrast as a function of beam energy. AB - Portal film contrast on a specially designed test phantom has been studied as a function of photon beam energy and object-to-film distance. The results provide important insights into the physical processes responsible for image contrast. In particular, theoretical calculations of Compton scatter reactions in the phantom can be used to predict visual film contrast. Good agreement between theory and experiment can be achieved by evaluating the double differential Compton cross sections [d sigma (E,theta)/dE d theta] in the test object without resorting to variable parameters or artificial normalization. These calculations demonstrate the importance of low-energy photons, object-to-film distance, and object size on portal film contrast. PMID- 3097465 TI - The neutron dose and energy spectrum outside a 20-MV accelerator treatment room. AB - A maze design is discussed for a Therac 20 linear accelerator (manufactured by Atomic Energy of Canada, Ltd.) which reduces the flux of neutrons at the door to permissible levels in controlled areas. The L-shaped design allows for a relatively light door at the end of the maze, consisting of 5.08-cm (2-in.) borated polyethylene and 2-mm lead. A comparison is made between the neutron dose equivalent (DE) calculated by various methods and the DE measured with a variety of portable neutron survey meters. In addition, the neutron energy spectrum outside the maze at 1 m from the door, measured with a polyethylene multisphere LiI system, is reported. PMID- 3097466 TI - Clarification of the AAPM Task Group 21 protocol. AB - In light of recent questions and comments from the physics community, a review is made of the AAPM protocol for high-energy x-ray and electron beam dosimetry. PMID- 3097467 TI - Comments on "Photonuclear activation ratios in fluorine compounds; an index of bremsstrahlung quality". PMID- 3097468 TI - [Possibilities, problems and limits of the conservative acute therapy and long term prevention of gastroduodenal ulcer disease]. PMID- 3097469 TI - [Molsidomine in rest and exercise conditions in coronary heart disease. Acute and long-term effects]. PMID- 3097470 TI - [Diverticulum excision and myotomy in the treatment of Zenker diverticulum]. PMID- 3097471 TI - [Clinicopathologic conference. Upper abdominal pain, postprandial vomiting and weight loss in a 50-year-old male: manifestation of an intraduodenal diverticulum]. PMID- 3097473 TI - [Internal medicine experiences with complete parenteral nutrition via the peripheral veins]. PMID- 3097472 TI - [Medium-chain triglycerides as a component of parenteral nutrition]. PMID- 3097474 TI - [Late symptoms following long-term artificial respiration in patients of an internal medicine intensive care unit. Catamnestic study after 1 to 3 years]. PMID- 3097475 TI - [Primary idiopathic intestinal pseudo-obstruction]. PMID- 3097476 TI - [New developments in ulcer therapy: famotidine, omeprazole misoprostol]. PMID- 3097477 TI - [Incidence of unrecognized, manifest and latent hyperthyroidism in an internal medicine patient sample]. PMID- 3097478 TI - [Hypertrophic cardiomyopathy in a patient with von Recklinghausen neurofibromatosis]. PMID- 3097479 TI - [Ground rules in parenteral nutrition]. PMID- 3097480 TI - [Long-term oxygen therapy in chronic obstructive disorders of ventilation]. PMID- 3097481 TI - Hemodilution and autotransfusion in pediatric cardiac surgery. AB - Better understanding and advances in the management of neonates undergoing cardiac surgery have increased their survival. Twenty neonates were studied to evaluate the technique of acute hemodilution in open cardiac surgery. They were premedicated by rectal barbiturate, anesthetized and monitored for all vital signs and blood chemistry. Patients operated upon with hemodilution suffered less respiratory acidosis during bypass. They showed marked drop in pH which was rapidly corrected in the postoperative period. No significant change in blood pressure from the expected was observed. These neonates (with hemodilution) had more tendency to fluid retention, which is not of appreciable clinical significance. The technique of acute hemodilution in neonates undergoing open cardiac surgery with extracorporeal circulation proved to be successful. PMID- 3097482 TI - [The dental and oral picture in a rare case of Morquio's syndrome]. PMID- 3097483 TI - Tube feeding: is it ever necessary? PMID- 3097484 TI - NIOSH recommendations for occupational safety and health standards. September 1986. PMID- 3097485 TI - Premature mortality in the United States: public health issues in the use of years of potential life lost. PMID- 3097486 TI - Smoking and health: a national status report. PMID- 3097487 TI - Premature mortality from diabetes mellitus--use of sentinel health event surveillance to assess causes. PMID- 3097488 TI - Staphylococcal food poisoning from turkey at a country club buffet--New Mexico. PMID- 3097489 TI - Influenza activity in civilian and military populations and key points for use of influenza vaccines. PMID- 3097490 TI - Turtle-associated salmonellosis--Ohio. PMID- 3097491 TI - Smoking prevalence and cessation in selected states, 1981-1983 and 1985--the Behavioral Risk Factor Surveys. PMID- 3097492 TI - Workplace smoking survey--New York City. PMID- 3097493 TI - Tularemia--New Jersey. PMID- 3097494 TI - Multiply resistant shigellosis in a day-care center--Texas. PMID- 3097495 TI - 1986 Surgeon General's report: the health consequences of involuntary smoking. PMID- 3097497 TI - Dengue hemorrhagic fever--Puerto Rico. PMID- 3097496 TI - Rubella and congenital rubella syndrome--New York City. PMID- 3097498 TI - Update: influenza activity--United States, worldwide. PMID- 3097499 TI - Mechanism of zone-specific hepatic steatosis caused by valproate: inhibition of ketogenesis in periportal regions of the liver lobule. AB - Microvacuolar steatosis in periportal regions of the liver lobule was produced by injection of fasted rats with a single dose of valproate (500 mg/kg, subcutaneously). In livers perfused in the absence of exogenous fatty acids, ketone body (acetoacetate + beta-hydroxybutyrate) production was decreased by valproate (500 microM) maximally by 67%. Concomitantly, NADH fluorescence detected from the liver surface declined about 30% with a time course similar to that of the inhibition of ketogenesis. Valproate had little effect on oxygen uptake but caused an elevation of the steady state level of catalase-H2O2 corresponding to an increase in H2O2 production of about 6 mumol/g/hr. In addition, valproate decreased the rate of oxidized glutathione release into bile by 45% but had little effect on bile flow. In the presence of oleate (250 microM), valproate inhibited ketone body production by 46% and decreased NADH fluorescence by 39%. Rates of ketogenesis in periportal and pericentral regions of the liver lobule were calculated from changes in NADH fluorescence detected with micro-light guides during infusion of valproate in the presence and absence of fatty acids. In the absence of valproate, endogenous ketogenesis was about 35 mumol/g/hr in both regions of the liver lobule. In the presence of oleate, however, rates were significantly higher in pericentral regions (89 +/- 2 mumol/g/hr) than in periportal areas (71 +/- 3 mumol/g/hr). In the presence of added oleate, valproate decreased rates of ketogenesis to 34 +/- 4 mumol/g/hr in periportal regions and 51 +/- 3 mumol/g/hr in pericentral areas. We conclude, therefore, that fat accumulates in periportal areas because valproate depresses ketogenesis to a greater extent in hepatocytes localized around the portal triad. PMID- 3097500 TI - Isolation and purification of rat liver morphine UDP-glucuronosyltransferase. AB - A UDP-glucuronosyltransferase (UDPGT) isoenzyme capable of morphine glucuronidation has been purified to apparent homogeneity and partially characterized from hepatic microsomes of female Wistar rats which have low 3 alpha-hydroxysteroid UDPGT. A rapid and sensitive assay was developed to quantify morphine glucuronide formation using 14C-UDP-glucuronic acid and reverse phase C 18 minicolumns whereby radioactive glucuronides were differentially eluted from 14C-UDP-glucuronic acid. Trisacryl-DEAE and chromatofocusing chromatographic procedures were employed to separate and purify morphine UDPGT in the presence of exogenous phosphatidylcholine. The addition of phospholipid was necessary to stabilize UDPGT activities throughout the purification procedures. Morphine UDPGT was isolated to apparent homogeneity and displayed a pl of 7.9 upon chromatofocusing. A monomeric molecular weight of 56,000 was obtained. The purified enzyme reacted with morphine but not with 4-hydroxybiphenyl, p nitrophenol, testosterone, androsterone, estrone, bilirubin, 4-aminobiphenyl, or alpha-naphthylamine. The MgCl2 requirement for maximal expression of morphine glucuronidation was higher for the purified enzyme than for solubilized and intact microsomes. Codeine competitively inhibits morphine glucuronidation with an apparent Ki of 1.1 mM with the purified morphine UDPGT. 4-Hydroxybiphenyl UDPGT was separated from morphine UDPGT using a chromatofocusing procedure for Emulgen 911-solubilized microsomes. An apparent pl value of 5.5 was obtained for this protein. Based on this work we conclude that morphine and 4-hydroxybiphenyl can react with separate UDPGT isoforms. PMID- 3097501 TI - Cell-type-specific synthesis of murine immunoglobulin mu RNA from an adenovirus vector. AB - The mouse immunoglobulin heavy-chain mu constant region gene was cloned into the early region 1B of an adenovirus type 5 vector to allow reproducible kinetics of expression of the mu gene in the presence of continuous host protein synthesis after infection by the recombinant. The immunoglobulin-adenovirus recombinant is helper independent in infecting human fibroblastic and B- and T-cell lines and expresses mu in a cell-type-specific manner. By Northern blot analysis, correctly polyadenylated and spliced E1B-mu S and E1B-mu m mRNAs are found to be equally abundant at steady state in fibroblasts. In contrast, and appropriately, only E1B mu S mRNAs accumulate in a lambda light-chain-secreting myeloma cell line. Analysis of nascent transcripts pulse labeled in isolated nuclei demonstrates equimolar polymerase loading throughout the mu region in all cell types infected by mu-Ad. Thus, correct polyadenylation and splicing of E1B-mu S and E1B-mu m in fibroblasts does not require transcription termination in the region separating the mu S and mu m polyadenylation sites. Furthermore, differential expression of mu transcripts in the background of myeloma cells is regulated at the level of RNA processing and does not require the presence of the immunoglobulin heavy chain enhancer or promoter element. PMID- 3097502 TI - Sequences involved in temperature and ecdysterone-induced transcription are located in separate regions of a Drosophila melanogaster heat shock gene. AB - The transcriptional regulation of the Drosophila melanogaster hsp27 (also called hsp28) gene was studied by introducing altered genes into the germ line by P element-mediated transformation. DNA sequences upstream of the gene were defined with respect to their effect on steroid hormone-induced and heat-induced transcription. These two types of control were found to be separable; the sequences responsible for 80% of heat-induced expression were located more than 1.1 kilobases upstream of the RNA initiation site, while the sequences responsible for the majority of ecdysterone induction were positioned downstream of the site at -227 base pairs. We have determined the DNA sequence of the intergenic region separating hsp23 and hsp27 and have located putative heat shock and ecdysterone consensus sequences. Our results indicate that the heat shock promoter of the hsp27 gene is organized quite differently from that of hsp70. PMID- 3097503 TI - A specific DNA sequence controls termination of transcription in the gastrin gene. AB - We located and characterized a downstream transcriptional regulatory element in the human gastrin gene by transferring the gastrin gene 3' fragment, from which the polyadenylation signal sequence was deleted, into the shuttle vector pSCAT10 at a site located immediately downstream from the chloramphenicol acetyltransferase (CAT) gene and upstream from the simian virus 40 polyadenylation region. Study of CAT RNA derived from the hybrid plasmids, indicated regulation of transcription on the gastrin gene fragment. Analysis of deletion mutants generated from the 5' region of the fragment by CAT assay and by S1 nuclease mapping of mRNAs indicated the possible involvement of an oligothymidylate-rich sequence in transcription regulation. Mapping of gastrin gene RNA 3' ends to the 5' side proximal to the oligothymidylate-rich sequence clearly demonstrated that this sequence is a transcriptional terminator element. This unique sequence, interspersed with one or two adenines, which also functions in an orientation-dependent manner, is located 192 nucleotides downstream from the gastrin gene polyadenylation site, and serves as a transcriptional termination signal. PMID- 3097505 TI - Oncogene-induced transformation of a rat embryo fibroblast cell line is enhanced by tumor promoters. AB - Rat embryo fibroblast cell line 6 was transfected with plasmid pT24, which contains the activated human bladder c-Ha-ras oncogene, and the cells were grown continuously in the absence or presence of the tumor promoters 12-O-tetradecanoyl phorbol-13-acetate (TPA) or teleocidin. The presence of TPA or teleocidin led to a 6- to 14-fold increase in the number of morphologically transformed foci. No transformed foci were seen when rat 6 cells were transfected with the normal c-Ha ras oncogene in the absence or presence of TPA, or in cells simply treated with TPA or teleocidin. Enhancement of pT24-induced foci was seen even when the addition of TPA was delayed until day 16. In transfection studies with the drug resistance genes gpt and neo, TPA and teleocidin did not increase the number of Gpt+ or Neo+ colonies. When rat 6 cells were cotransfected with pT24 and neo genes and grown in the absence or presence of TPA, the presence of TPA did not increase the yield of Neo+ colonies but caused a fivefold increase in the number of Neo+ colonies that displayed a transformed morphology. Southern blot analyses of DNAs obtained from these clones indicated that TPA treatment did not influence the extent of integration of either the pT24 or neo gene. DNA samples from all of the morphologically transformed cells displayed a characteristic 2-kilobase SacI fragment homologous to pT24 DNA and expressed relatively high levels of the corresponding mRNA. Our findings indicate that in this system tumor promoters do not simply enhanced the process of DNA transfection per se. Thus, this model system may be useful for analyzing synergistic interactions between tumor promoters and activated oncogenes during multistage carcinogenesis. It may also serve as a simple screening test for detecting new tumor promoters. PMID- 3097504 TI - Large changes in intracellular pH and calcium observed during heat shock are not responsible for the induction of heat shock proteins in Drosophila melanogaster. AB - Heat shock caused significant changes in intracellular pH (pHi) and intracellular free calcium concentration [( Ca2+]i) which occurred rapidly after temperature elevation. pHi fell from a resting level value at 25 degrees C of 7.38 +/- 0.02 (mean +/- standard error of the mean, n = 15) to 6.91 +/- 0.11 (n = 7) at 35 degrees C. The resting level value of [Ca2+]i in single Drosophila melanogaster larval salivary gland cells was 198 +/- 31 nM (n = 4). It increased approximately 10-fold, to 1,870 +/- 770 nM (n = 4), during a heat shock. When salivary glands were incubated in calcium-free, ethylene glycol-bis(beta-aminoethyl ether) N,N',N'-tetraacetic acid (EGTA)-buffered medium, the resting level value of [Ca2+]i was reduced to 80 +/- 7 nM (n = 3), and heat shock resulted in a fourfold increase in [Ca2+]i to 353 +/- 90 nM (n = 3). The intracellular free-ion concentrations of Na+, K+, Cl-, and Mg2+ were 9.6 +/- 0.8, 101.9 +/- 1.7, 36 +/- 1.5, and 2.4 +/- 0.2 mM, respectively, and remained essentially unchanged during a heat shock. Procedures were devised to mimic or block the effects of heat shock on pHi and [Ca2+]i and to assess their role in the induction of heat shock proteins. We report here that the changes in [Ca2+]i and pHi which occur during heat shock are not sufficient, nor are they required, for a complete induction of the heat shock response. PMID- 3097506 TI - Two Drosophila melanogaster tropomyosin genes: structural and functional aspects. AB - We compared the structure and function of the two Drosophila melanogaster tropomyosin genes. The most striking structural aspect was their size disparity. Codons 1 through 257 of gene 2 occupied 833 nucleotides and contained only one intron, whereas the corresponding region of gene 1 occupied 17.5 kilobases and was interrupted by eight introns. The intron-exon arrangement of gene 1 reflected evolutionary expansion of tropomyosin via 42- and 49-residue duplications, which are probably actin-binding domains. Functionally, gene 1 was considerably more complex than gene 2; it was active in both muscle and nonmuscle cell lineages, had at least five variable exons, and specified a minimum of five developmentally regulated isoforms. Two of these isoforms, which accumulated only in flight muscles, were unprecedented fusion proteins in which the tropomyosin sequence was joined to a carboxy-terminal proline-rich domain. PMID- 3097507 TI - Sequence requirement for expression of the Drosophila melanogaster heat shock protein hsp22 gene during heat shock and normal development. AB - A 14-base-pair sequence element present in almost all Drosophila melanogaster heat shock genes has been implicated in the heat inducibility of transcription. The D. melanogaster gene encoding the smallest heat shock protein, hsp22, contains within its 5' flanking sequences three such repeats, two close to the transcription start site and a distally located third one 101 base pairs further upstream. Deletion analyses reveal that the 5' flanking sequences required for full expression of the hsp22 gene extend beyond the distal repeat. Deletion of the furthest upstream repeat results in a five to sixfold reduction of gene expression. The small heat shock genes are transiently expressed in the late third instar larval and early pupal stages without external stimulation. A deletion of 5' flanking sequences to position -194, which includes two nucleotides of the distal heat shock element, has no effect on the developmental expression, whereas removal of an additional 18 nucleotides, including 12 nucleotides of the distal heat shock element, severely reduces developmental expression. PMID- 3097508 TI - Regulation of synthesis and turnover of an interferon-inducible mRNA. AB - Regulation of synthesis and turnover of an interferon (IFN)-inducible mRNA, mRNA 561, in HeLa monolayer cells was studied. Cytoplasmic levels of this mRNA were estimated by hybridization analyses with a cDNA clone that we have isolated as a probe. IFN-alpha A induced a high level of this mRNA in a transient fashion, whereas no induction was observed in response to IFN-gamma. Surprisingly little mRNA 561 was induced in cells treated simultaneously with IFN-alpha A and an inhibitor of protein synthesis, suggesting that in addition to IFN-alpha A, an interferon-inducible protein was needed for induction of this mRNA. Apparently this putative protein could be induced by IFN-gamma as well. Thus, although little mRNA 561 was synthesized in cells treated either with IFN-gamma alone or with IFN-alpha A and cycloheximide, a large quantity of this mRNA was induced in cells which had been pretreated with IFN-gamma and then treated with IFN-alpha A and cycloheximide. Once mRNA 561 was induced by IFN-alpha A, it turned over rapidly. This rapid turnover could be blocked by actinomycin D or cycloheximide indicating that another IFN-inducible protein may mediate this process. PMID- 3097509 TI - The Drosophila melanogaster actin 5C gene uses two transcription initiation sites and three polyadenylation sites to express multiple mRNA species. AB - At least six mRNAs are made from the Drosophila melanogaster act5C gene. We investigated the structures of these RNAs in detail and determined that they are heterogeneous at both their 5' and 3' ends. At the 5' end there were two nonhomologous leader exons which were alternately spliced to the remainder of the gene. These leader exons mapped to 1.7 and 0.7 kilobases, respectively, upstream of a common splice acceptor site which was eight base pairs 5' to the translation initiator AUG. Exon 1 is 147 bases in length, while exon 2 is 111 bases. A consensus TATA sequence was found roughly 30 base pairs upstream from exon 1, but none was found in the analogous position upstream of exon 2. The transcript length diversity arose principally from the use of three polyadenylation sites. This gave rise to RNA molecules with 3'-untranslated regions of roughly 375, 655, and 945 base pairs. With two start sites and three termination sites, this gene has the potential to produce six different transcripts. All six possible transcripts were present in whole fly mRNA. Transcripts containing the two different leader exons were found in roughly the same relative quantities through development. In contrast, the various 3' ends were differentially represented through development. PMID- 3097511 TI - Posttranscriptional control of human gamma interferon gene expression in transfected mouse fibroblasts. AB - Human gamma interferon genomic DNA was introduced into NIH 3T3 fibroblasts by calcium phosphate precipitation and was not expressed in these cells at the cytoplasmic mRNA or protein level. Treatment of the transfected cells with cycloheximide (1 microgram/ml) induced the accumulation of cytoplasmic gamma interferon mRNA and biologically active human gamma interferon. Analysis of the nuclear enriched RNA from untreated cells indicated that human gamma interferon mRNA was present, suggesting that cycloheximide may act by inhibiting a specific nuclease or may enhance the processing or transport of the RNA from the nucleus to the cytoplasm. PMID- 3097510 TI - Tissue localization of Drosophila melanogaster ras transcripts during development. AB - Three ras homologs have been identified in Drosophila melanogaster. Here we describe the tissue distribution of their transcripts as analyzed by in situ hybridization. The RNAs of the three genes show a similar distribution at every developmental stage examined. In embryos, the transcripts are uniformly distributed. In larvae, ras transcripts are restricted to dividing cells (e.g., imaginal disks, gonads, and brain). At the adult stage, several tissues contain ras transcripts. The strongest hybridization signals are localized to the adult ovaries and to the cortex of the brain and ganglia, which at this stage are comprised of differentiated, nondividing cells. The tissue distribution of ras transcripts in D. melanogaster suggests that the ras proteins have multiple roles during development which may be related to both the proliferative and differentiated states of the tissues. PMID- 3097512 TI - Short repeated elements in the upstream regulatory region of the SUC2 gene of Saccharomyces cerevisiae. AB - Expression of secreted invertase from the SUC2 gene is regulated by carbon catabolite repression. Previously, an upstream regulatory region that is required for derepression of secreted invertase was identified and shown to confer glucose repressible expression to the heterologous promoter of a LEU2-lacZ fusion. In this paper we show that tandem copies of a 32-base pair (bp) sequence from the upstream regulatory region activate expression of the same LEU2-lacZ fusion. The level of expression increased with the number of copies of the element, but was independent of their orientation; the expression from constructions containing four copies of the sequence was only twofold lower than that when the entire SUC2 upstream regulatory region was present. This activation was not significantly glucose repressible. The 32-bp sequence includes a 7-bp motif with the consensus sequence (A/C)(A/G)GAAAT that is repeated at five sites within the upstream regulatory region. Genetic evidence supporting the functional significance of this repeated motif was obtained by pseudoreversion of a SUC2 deletion mutant lacking part of the upstream region, including two copies of the 7-bp element. In three of five pseudorevertants, the mutations that restored high-level SUC2 expression altered one of the remaining copies of the 7-bp element. PMID- 3097513 TI - Activation of the cellular src gene by transducing retrovirus. AB - Newly isolated strains of avian sarcoma virus, S1 and S2, were shown to have the transduced cellular src gene as their viral transforming gene (Yamagishi et al., Virology 137:266-275, 1984). In this work, the S1 and S2 genomes were molecularly cloned, and the junction sequences between the viral genomes and the c-src genes and the complete nucleotide sequences of the v-src genes transduced in these viruses were determined. Data on the junction sequences suggested that 5' recombination had occurred between the 5'-noncoding region of c-src and the 5' region of the gag sequence encoding p19 in both viruses and that 3' recombination had occurred in the last coding exon of c-src with either the middle portion of the env sequence encoding gp85 for S1 or the 3' portion of pol coding for reverse transcriptase for S2. Comparison of the amino acid sequences of the S1 and S2 src products deduced from the nucleotide sequences (pp62S1-src and pp62S2-src with that of c-src protein (pp60c-src) indicated that in pp62S1-src the 8 carboxy terminal amino acid residues of the total of 533 in pp60c-src are replaced by 43 residues translated from the env sequence at the wrong frame. In pp62S2-src, on the other hand, the 14 carboxy-terminal amino acids of pp60c-src are replaced by the 38 carboxy-terminal residues of reverse transcriptase. The mechanism of c-src transduction and the structural changes necessary for pp60c-src activation are discussed. PMID- 3097514 TI - Features of the pp60v-src carboxyl terminus that are required for transformation. AB - Analysis of the biological and biochemical activities of pp60recombinant-src proteins encoded by 12 carboxyl-terminal mutants showed that a wide family of alternate src carboxyl termini permit complete transforming and kinase activities. src proteins having carboxyl termini which are up to 10 amino acids longer than that of pp60c-src (17 amino acids longer than that of pp60v-src) still permit transformation. Transformation-positive mutations preserve leucine 516, a residue which is highly conserved in protein-tyrosine kinase sequences; removal causes in vivo protein instability. Successive deletion mutants show that this residue is at the boundary of a region required for kinase activity. pp60src which is truncated just outside this point still transforms cells and binds both pp50 and pp90 cellular proteins. PMID- 3097515 TI - The ubiquitous potential Z-forming sequence of eucaryotes, (dT-dG)n . (dC-dA)n, is not detectable in the genomes of eubacteria, archaebacteria, or mitochondria. AB - The potential Z-forming sequence (dT-dG)n . (dC-dA)n is an abundant, interspersed repeat element that is ubiquitous in eucaryotic nuclear genomes. We report that in contrast to eucaryotic nuclear DNA, the genomes of eubacteria, archaebacteria, and mitochondria lack this sequence, since even a single tract of greater than or equal to 14 base pairs in length is not detectable through either hybridization or sequence analysis. Interestingly, the phylogenetic distribution of the (dT dG)n . (dC-dA)n repeat exhibits a striking parallel to that of (dT-dC)n . (dG dA)n, but not to other homocopolymeric sequences such as (dC-dG)n . (dC-dG)n or (dT-dA)n . (dT-dA)n. PMID- 3097516 TI - Transcriptional control of glucoamylase synthesis in vegetatively growing and sporulating Saccharomyces species. AB - Three unlinked, homologous genes, STA1, STA2, and STA3, encode the extracellular glycosylated glucoamylase isozymes I, II, and III, respectively, in Saccharomyces species. S. cerevisiae, which is sta0 (absence of functional STA genes in haploids), does carry a glucoamylase gene, delta sta, expressed only during sporulation (W. J. Colonna and P. T. Magee, J. Bacteriol. 134:844-853, 1978; I. Yamashita and S. Fukui, Mol. Cell. Biol. 5:3069-3073, 1985). In this study we examined some of the physiological and genetic factors that affect glucoamylase expression. It was found that STA2 strains grown in synthetic medium produce glucoamylase only in the presence of either Maltrin M365 (a mixture of maltooligosaccharides) or starch. Maximal levels of glucoamylase activity were found in cells grown in rich medium supplemented with glycerol plus ethanol, starch, or Maltrin. When various sugars served as carbon sources they all supported glucoamylase synthesis, although at reduced levels. In any given growth medium glucoamylase isozyme II synthesis was modulated by functionality of the mitochondria. Synthesis of glucoamylase is continuous throughout the growth phases, with maximal secretion taking place in the early stationary phase. In the various regimens, the differences in enzyme accumulation are accounted for by differences in the levels of glucoamylase mRNA. Both glucoamylase mRNA and enzyme activity were drastically and coordinately inhibited in MATa/MAT alpha diploids and by the presence of the regulatory gene STA10. Both effects were partially overcome when the STA2 gene was present on a multicopy plasmid. The STA2 mRNA and glucoamylase were coinduced in sporulating STA2/STA2 diploids. A smaller, coinduced RNA species was also detected by Northern blotting with a STA2 probe. The same mRNA species was detected in sporulating sta0 diploids and is likely to encode the sporulation-specific glucoamylase. PMID- 3097517 TI - Sequence of the notch locus of Drosophila melanogaster: relationship of the encoded protein to mammalian clotting and growth factors. AB - The Notch locus is essential for proper differentiation of the ectoderm in Drosophila melanogaster. Notch corresponds to a 37-kilobase transcription unit that codes for a major 10.4-kilobase polyadenylated RNA. The DNA sequence of this transcription unit is presented, except for portions of the two largest intervening sequences. DNA sequences also were obtained from three Notch cDNA clones, allowing the 5' and 3' ends of the gene to be mapped, and the structures and locations of nine RNA coding regions to be determined. The major Notch transcript encodes a protein of 2,703 amino acids. The protein is probably associated with cell surfaces and carries an extracellular domain composed of 36 cysteine-rich repeating units, each of about 38 amino acids. The gene appears to have evolved by repeated tandem duplications of the DNA coding for the 38-amino acid-long protein segments, followed by insertion of intervening sequences. These repeating protein segments are quite homologous to portions of mammalian clotting factors IX and X and to the product of the Caenorhabditis elegans developmental gene lin-12. They are also similar to mammalian growth hormones, typified by epidermal growth factor. PMID- 3097519 TI - Contribution of the VK4 light chain to antibody specificity for lysozyme and beta (1,6)D-galactan. AB - The VL amino acid sequence of an anti-lysozyme hybridoma protein, HyHEL-5, was determined. HyHEL-5 expresses a V region of the VK4 family and JK1. The VK4 family also includes light chains from galactan binding antibodies, although sequence comparisons suggest that a different member of this family is used to encode HyHEL-5. The HyHEL-5 light chain has a deletion of residue 96, such that L3 is one residue shorter than the majority of murine L3. Chain recombination experiments, employing H and L chains from different anti-galactan and anti lysozyme binding antibodies, were performed to examine the contribution of the H and L chain in dictating specificity for either galactan or the lysozyme epitope recognized by HyHEL-5. The results indicate that, although the ability to bind galactan vs lysozyme is absolutely heavy-chain dependent, having the appropriate heavy chain is not sufficient for specific high affinity binding. Both the L chains from HyHEL-5 and J539 (a galactan-binding myeloma protein) were capable of supporting binding to galactan in combination with the J539 H chain, but affinity for galactan is less with the HyHEL-5 L chain. Only VK4 L chains supported binding of the HyHEL-5 heavy chain to the HyHEL-5 epitope, although binding with the J539 L chain was low affinity and relatively nonspecific. PMID- 3097518 TI - rasH mutants deficient in GTP binding. AB - Single amino acid substitutions were introduced into a region of the rasH protein (residues 116, 117, and 119) homologous to a variety of diverse GTP-binding proteins. Each of the mutant p21 proteins displayed a significant reduction (10- to 5,000-fold) in GTP binding affinity. Activated rasH proteins deficient in GTP binding were unaltered in their ability to morphologically transform NIH 3T3 cells. PMID- 3097520 TI - High level stable expression of human interleukin-2 receptors in mouse cells generates only low affinity interleukin-2 binding sites. AB - A bovine papilloma virus-derived vector was used to direct the high level expression in mouse C127 cells of three different cDNAs encoding the human interleukin-2 receptor. These were: the previously described cDNA clone isolated from the T-cell lymphoma, HUT-102; a cDNA clone isolated from mitogen-activated, normal peripheral blood T cells; and an altered version of the HUT-102 receptor in which Ser247, believed to be the site of protein kinase C-mediated phosphorylation, has been changed to an Ala residue. Fluorescence-activated cell sorting using a monoclonal antibody directed against the human IL-2 receptor was used to derive stable lines of C127 cells expressing from 2-6 X 10(6) IL-2 binding sites per cell. However, all of these receptors bound IL-2 with low affinity. PMID- 3097521 TI - Antibody Fab assembly: the interface residues between CH1 and CL. AB - The effective assembly of an antibody molecule requires the proper association of the light and heavy chains, namely the tight, canonical association of VH with VL, and of CH1 with CL. In this paper the interaction of CH1 is examined by looking at the degree of conservation of residues in the interface between CH1 and CL, where CH1 can belong to any of the heavy chain classes, and CL can be either lambda or kappa. The three-dimensional structures of four antibody Fabs have been examined to see which are the significant interacting residues and to see whether they also correspond to the conserved residues in the different classes. It was found that there are a few hydrophobic residues buried in the interface which make numerous contacts with residues of the other chain and which remain invariant, or else are highly conserved. Around the periphery of the interface there are numerous interacting residues that have appreciable variability. Within the interface there is a cavity, the function of which may be to permit some changes in the central interface residues while still preserving the same relative orientation of CH1 and CL. PMID- 3097522 TI - [Disorders of bone metabolism in premature infants]. AB - Extremely low birth weight infants are particularly prone to rickets (osteopenia) due to their rapid growth and to deficient intake of calcium and phosphate. In some premature infants suffering from phosphate depletion hypercalcemia syndrome may precede bone demineralisation. Additionally, the adverse effects of calciprivic drugs (phenytoin, phenobarbital, glucocorticoids, furosemide, heparin) contributing to the development of neonatal rickets are discussed. Phosphorus depleted or heparin treated experimental animals develop impairment of mineralisation as manifested by rickets or osteomalacia. Some clinical cases of neonatal rickets are reported and a dosage schedule for parenteral infusion of minerals is given. PMID- 3097523 TI - [Development of the electroencephalogram and the significance of neonatal convulsions in premature infants]. AB - The anatomic maturation of the brain of preterm babies of 28-36 weeks of gestational age is characterized by an increase in continuity by a differentiation in behavior states in the EEG pattern. The EEG results are essential in the diagnosis of seizures in preterm babies. For the prognosis of these seizures the etiology and the gestational age also have to be taken into consideration. An amelioration of the prognosis of neonatal seizures is possible by adequate therapy. PMID- 3097524 TI - [Hemolytic uremic syndrome following juvenile lupus erythematodes disseminatus]. AB - A 12.5 year old girl was admitted to hospital with the typical signs of hemolytic uremic syndrome, and systemic lupus erythematodes as well. On the basis of clinical, blood chemistry, and histological findings we assumed an hemolysis induced form of hemolytic-uremic syndrome as the most likely pathogenic mechanism. The child also suffered from congenital IgA-deficiency and produced an inhibitor against coagulation factor VIII. Congenital IgA-deficiency, systemic lupus erythematodes, inhibitor-induced hemophilia and hemolytic uremic syndrome are suggested to form a pathogenic sequence. PMID- 3097525 TI - [Design of a recombinant plasmid allowing the selection of an optimal promotor for the human interferon alpha2 gene]. PMID- 3097526 TI - [Immunoelectrophoretic identification of the molecular heterogeneity of meningococcal serogroup polysaccharides]. PMID- 3097528 TI - [Rapid method for analyzing the plasmid DNA of Bacillus cereus]. PMID- 3097527 TI - [Expression of the artificial gene for human leukocyte interferon alpha 2 cloned in phage M13MP8]. PMID- 3097529 TI - [Genetic determinants of resistance to streptomycin and sulfanilamides in Pseudomonas aeruginosa and enterobacteria]. PMID- 3097530 TI - Kinetic determination of enzymatic activity and modification of the metabolic activation system in the SOS chromotest. AB - The "SOS Chromotest" has recently been introduced by P. Quillardet et al. (1982; Quillardet and Hofnung, 1985), who use strain PQ37 of Escherichia coli K12 to test for genotoxicity. We have modified the procedure in order to optimize the determination of beta-galactosidase and alkaline phosphatase activities, and, where possible, to allow measurements to be made automatically. Kinetic determination is quicker, more sensitive and avoids interference by coloured compounds. Modification of the metabolic activation system increases the sensitivity of the test for progenotoxicity. PMID- 3097531 TI - Qualitative differences between replicative and repair synthesis of DNA in normal and transformed mouse cells as measured by precursor discrimination. AB - Inhibitors of DNA polymerase alpha such as aphidicolin (APC) or 1-beta-D arabinofuranosyl-cytosine (araC) cause DNA-strand breaks to accumulate after UV irradiation, at sites where repair resynthesis is inhibited. Transformed cells accumulate fewer such breaks than normal cells do; this may be due to differences in the extent, or the nature, of excision-repair synthesis in transformed and in normal cells. We have looked for differences in the nature of repair synthesis, comparing the labelling of DNA by deoxycytidine (dC) and araC through UV-induced repair in normal and transformed mouse cells. We have made parallel determinations of precursor discrimination in replicative synthesis, and find that normal cells discriminate better against araC in replicative synthesis than do transformed cells. But repair synthesis discriminates against araC less than normal replicative synthesis does, to a similar extent in both cell types. Thus, there are qualitative differences between the DNA polymerases engaged in UV excision repair and replication in normal and transformed mouse cells; but there is no evidence for a predominantly araC-insensitive repair synthesis in transformed cells, such as might account for the difference in break accumulation. PMID- 3097532 TI - Indication for weak mutagenicity of the organophosphorus insecticide dimethoate in Drosophila melanogaster. AB - The organophosphorus insecticide dimethoate was tested for induction of genetic damage in male germ cells of Drosophila melanogaster. Sex-linked recessive lethals, sex-chromosome loss and non-disjunction induction were studied following different routes of administration: adult feeding, injection and larval feeding. Our results show that, after injection, dimethoate induces a slight but significant increase in the frequency of point mutations. PMID- 3097533 TI - Endogenous promutagen activation in the yeast Saccharomyces cerevisiae: factors influencing aflatoxin B1 mutagenicity. AB - The formation of convertants, revertants and other types of mitotic segregants was induced in Saccharomyces cerevisiae D7 upon incubation with aflatoxin B1 (AFB1). The most distinct effects were observed for gene conversion to tryptophan prototrophy. The fact that different cytochrome P-450 inhibitors (ellipticine, penconazole and propiconazole as yeast-specific P-450 inhibitors) abolished the AFB1-induced mutagenicity indicates that activation of the promutagen AFB1 depends on the cytochrome P-450-catalyzed electron-transfer reactions. This hypothesis is further supported by the observation that the cytochrome P-450 content of yeast cells harvested at different phases during growth is directly correlated with their sensitivity for AFB1-induced tryptophan conversion. PMID- 3097535 TI - Physical assessment of the neonate. PMID- 3097534 TI - In vitro micronucleus method with erythropoietin-differentiated erythrocytes. AB - A new in vitro micronucleus method has been developed for the detection of chromosomal damage in mouse bone-marrow erythrocytes which are differentiated with erythropoietin (EPO). After the hemolysis of bone-marrow erythrocytes, newly formed polychromatic erythrocytes (PCEs) were observed in cultures incubated in the presence of EPO. Using the erythroid differentiation technique, increased frequencies of micronuclei were detected in PCEs after treatment with mitomycin C. In addition, the in vitro micronucleus method was found to be more sensitive than the in vitro chromosomal aberration test on Chinese hamster cells. The results show that the in vitro micronucleus method using EPO-differentiated erythrocytes is a highly sensitive and useful system for the detection of mutagens. PMID- 3097536 TI - Postpartum follow-up: a nursing practice guide. PMID- 3097537 TI - Basic research: does a need exist in nursing today? PMID- 3097538 TI - GTP-binding proteins associated with serotonin-activated adenylate cyclase in Fasciola hepatica. AB - The liver fluke Fasciola hepatica has serotonin (5-hydroxytryptamine) receptors that function through a transmembrane signalling system requiring GTP which activates adenylate cyclase (ATP pyrophosphate-lyase (cyclising), EC 4.6.1.1). Non-hydrolysable GTP analogs and NaF activate adenylate cyclase in membrane particles of these organisms. The nature of GTP-binding proteins in these membranes was studied using bacterial toxins and photoaffinity labelling. Treatment of membrane particles from flukes with cholera toxin increased basal adenylate cyclase activity, but markedly decreased activation by serotonin, non hydrolysable GTP analogs, and NaF. [32P]ADP-ribosylation by cholera toxin or photoaffinity labelling with [32P]-8-N3GTP identified a 53 kDa protein and a 45 kDa protein which appeared to be similar to the forms of the alpha-subunit of the GTP-binding protein associated with adenylate cyclase in mammals. Treatment of membrane particles by pertussis toxin did not significantly change basal adenylate cyclase activity and did not change the stimulation of cyclase by activators. A 43 kDa protein which was [32P]ADP-ribosylated by either cholera or pertussis toxin, depending on the conditions used, and photoaffinity labelled by [32P]-8-N3GTP may be part of the transmembrane signalling system in the liver flukes. PMID- 3097540 TI - Gonadotropin-releasing hormone: role of pulsatile secretion in the regulation of reproduction. PMID- 3097539 TI - Sequence and expression of a major egg antigen from Schistosoma mansoni. Homologies to heat shock proteins and alpha-crystallins. AB - One of the major proteins of eggs and miracidia (p40) of Schistosoma mansoni has an apparent molecular weight of 40,000 and elicits a strong immune response in over 90% of patients. The antigen consists of a family of at least four near identical proteins, probably encoded by a multi-gene family, and expression of the p40 polypeptides is differentially regulated around the parasite's life cycle. We have isolated and sequenced cDNA clones encoding two variants of the antigen and expressed one p40 clone in Escherichia coli. The fusion protein elicits antibodies which immunoprecipitate p40 and recognise antigens of identical sizes in S. haematobium and S. bovis. The open reading frame encoding this antigen specifies a protein which shares a block of sequence homology with alpha-crystallins and Drosophila small heat shock proteins. PMID- 3097542 TI - Eye findings in bilateral acoustic (central) neurofibromatosis: association with presenile lens opacities and cataracts but absence of Lisch nodules. PMID- 3097541 TI - Tetracycline-resistant Neisseria. PMID- 3097543 TI - Exogenous reinfection with tuberculosis in a shelter for the homeless. AB - We investigated an outbreak of tuberculosis in a large shelter for the homeless to assess the role of exogenous reinfection as opposed to reactivation of endogenous infection as the cause of secondary tuberculosis in this population. Exogenous reinfection is considered relatively unimportant in the United States and other developed countries. Of 49 shelter-related cases, 22 had cultures resistant to both isoniazid and streptomycin and of the same phage type, indicating recent transmission originating with a single index patient. The probable index patient had a 10-year history of isoniazid and streptomycin resistance--an uncommon pattern at the shelter during the three years preceding the outbreak. In 4 of the 22 cases, the patient had previously had documented tuberculosis infection or disease. These reinfected patients had extensive lung cavitation and numerous acid-fast bacilli on sputum smears--features associated with contagiousness. In contrast, patients with tuberculosis for the first time (primary tuberculosis) are usually less contagious. We conclude that exogenous reinfection may have been an important factor leading to highly contagious secondary cases and an acceleration of the usual pattern of tuberculosis transmission in this highly susceptible population. PMID- 3097544 TI - Treatment of chronic non-A,non-B hepatitis with recombinant human alpha interferon. A preliminary report. AB - We treated 10 patients who had chronic non-A,non-B hepatitis with recombinant human alpha interferon in varying doses (0.5 to 5 million units) daily, every other day, or three times weekly for up to 12 months. In 8 of the 10 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. In two of these patients, the interferon therapy was stopped after four months, and in both cases, a prompt return of aminotransferase activities to pretreatment values occurred. Prolonged treatment was associated with a sustained improvement in aminotransferase levels; in three cases, biopsy specimens obtained after one year of therapy showed marked improvement in hepatic histology, even though low doses of alpha interferon had been used. These preliminary findings, although not adequately controlled, suggest that long-term, low-dose alpha interferon therapy may be effective in controlling the disease activity in some patients with chronic non-A,non-B hepatitis. A prospective controlled trial is now needed to assess the role of interferon therapy in this disease. PMID- 3097545 TI - Lactose intolerance associated with Intal capsules. PMID- 3097546 TI - Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitation. PMID- 3097547 TI - Gastrostomy-tube jaundice. PMID- 3097548 TI - Cost-effectiveness of short-term tests for carcinogenicity. AB - Most chemicals to which we are exposed are not properly tested for carcinogenicity. The latest methods of in vitro testing provide a way of screening with sufficient accuracy to remedy this situation. PMID- 3097549 TI - Molecular evolution. Deciphering divergent codes. PMID- 3097551 TI - Technology: Genentech buys out partnerships. PMID- 3097550 TI - The t(8; 14) chromosomal translocation occurring in B-cell malignancies results from mistakes in V-D-J joining. AB - The reciprocal chromosome translocation, t(8;14), involving the heavy chain locus on chromosome 14 and the c-myc oncogene on chromosome 8 is a characteristic of the B-cell malignancies Burkitt's lymphoma and acute lymphoblastic leukaemia (ALL). We have cloned and sequenced the t(8; 14) breakpoints of an African Burkitt's lymphoma cell line, P3HR-1, and a pre-B cell ALL cell line, 380. In each case the region of chromosome 8 involved has recombined with a JH region on chromosome 14. The two sites of breakage on chromosome 8 lie within 70 base pairs (bp) of one another. At each joining site, sequences homologous to the signal sequences thought to be recognized by the V-D-J recombinase were identified, as were N regions. In B-cell chronic lymphocytic leukaemias (B-CLL) carrying the t(11; 14) chromosome translocation and in follicular lymphomas carrying the t(14; 18) translocation, the V-D-J recombinase is implicated in the mechanism of chromosomal translocations. We speculate that the same enzymatic mechanism is responsible for the t(8; 14) translocations in African Burkitt's lymphoma and pre B cell ALL. PMID- 3097552 TI - Migration and hominid bipedalism. PMID- 3097553 TI - Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots. AB - Haemophilia A is a common disorder of blood coagulation caused by a deficiency of factor VIII. It is inherited as an X-linked recessive trait, and one-third of all cases are thought to result from de novo mutations. The clinical severity of haemophilia A varies markedly among different families and a subset of the patients with severe disease develop antibodies against factor VIII, called inhibitors. Because of this heterogeneity, it is likely that many different molecular lesions result in haemophilia A. Indeed, of the nine mutations described to date, all appear to be unique changes. However in this study of 83 patients with haemophilia A we have identified two different point mutations, one in exon 18 and one in exon 22, that have recurred independently in unrelated families. Each mutation produces a nonsense codon by a change of CG to TG, and each occurred de novo on the X-chromosome donated by the maternal grandfather. These observations strongly support the view that CpG dinucleotides are mutation hotspots. PMID- 3097555 TI - BSF-2 is not just a differentiation factor. PMID- 3097554 TI - A protein on Plasmodium falciparum-infected erythrocytes functions as a transferrin receptor. AB - Several observations suggest that iron is essential for the development of malaria parasites but there is evidence that the parasites in erythrocytes do not obtain iron from haemoglobin. The total haemin level in parasitized erythrocytes does not vary during parasite development, indicating that the iron-containing moiety of haemoglobin is not detectably metabolized. Although parasite proteases can degrade the protein part of haemoglobin in red cells, no parasite enzymes that degrade haemin have been identified. In mammalian cells, haemin is degraded to carbon monoxide and bilirubin by the enzyme haeme oxygenase. This enzyme has not been found in malaria parasites. In fact haemin has been found to be toxic to parasite carbohydrate metabolism. Thus, iron apparently cannot be liberated from haemin and instead is sequestered in infected red cells as haemozoin, the characteristic pigment associated with malarial infection. If iron bound to transferrin is the source of ferric ions for malaria parasites within mature erythrocytes, then the parasite must synthesize its own transferrin receptor and localize it on the surface of the infected cell, because the receptors for transferrin are lost during erythrocyte maturation. Our results here suggest that Plasmodium falciparum synthesizes its own transferrin receptors enabling it to take up iron from transferrin by receptor-mediated endocytosis. PMID- 3097556 TI - A 40,000 year-old human occupation site at Huon Peninsula, Papua New Guinea. AB - The geographical position of the island of New Guinea suggests that it may have been an early staging post in the Pleistocene settlement of Australia from the Indonesia-Indochina region. Previous data have not supported this, as archaeological sites 35,000 to 40,000 years old occur in southern Australia, whereas the earliest previously known in Papua New Guinea is 26,000 years old. We now report evidence that the north coast of Papua New Guinea was occupied at least 40,000 years ago. Sahuland, which is the greater land area of Australia and New Guinea plus their connecting continental shelf exposed as land when Pleistocene sea levels were lower than now, was occupied by humans in several widely separated areas at that time. A distinctive 'waisted axe' culture appears to have existed in New Guinea and probably in Australia in the Late Pleistocene, but antecedents are not yet known from east and southeast Asia. There is evidence for hafting of these tools at a date which is earlier than known elsewhere in the world. PMID- 3097558 TI - The future of health care. PMID- 3097557 TI - The significance of the relative effects of loop diuretics and anti-brain edema agents on the Na+,K+,Cl- cotransport system and the Cl-/NaCO3- anion exchanger. AB - 3-Amino-5-sulfamoylbenzoic acids and several series of (aryloxy)alkanoic acids were evaluated for their inhibitory effects on two human erythrocyte ion transport systems--the Na+,K+ cotransport system and the DIDS-sensitive anion carrier. Several classic loop diuretics, including the (aryloxy)alkanoic acid ethacrynic acid and several 3-amino-5-sulfamoylbenzoic acids, like bumetanide and furosemide, displayed relatively strong inhibitory activity versus the cotransport system with relatively weaker action versus the anion carrier. Furthermore, diuretic potency correlated with cotransport inhibitory potency. Another class of (aryloxy)alkanoic acids, namely the [(2,3-dihydro-1H-inden-5 yl)oxy]acetic acids, such as indacrinone and MK-473, which exhibit less potent loop diuretic activity, were less potent cotransport inhibitors and more effective inhibitors of the anion carrier. Still other (aryloxy)alkanoic acids, with little saliuretic activity, namely a sub-class of [(2,3-dihydro-1H-inden-5 yl)oxy]alkanoic acids and a series of [(2,3,9,9a-tetrahydro-1H-fluoren-7 yl)oxy]acetic acids displayed little or no inhibitory action on the cotransport system but enhanced inhibitory action on the anion carrier. Most interestingly, the relative anion carrier inhibitory potency correlated well with the relative inhibitory activity of each compound on bicarbonate-stimulated cell swelling in cat cerebrocortical slices. PMID- 3097559 TI - Center-specific variations of thyroid hormone serum levels in hemodialysis patients. AB - Thyroid hormone (free and total thyroxine, total 3,5,3'- and 3,3'5' triiodothyronine, thyroxine-binding globulin, thyrotropin) serum concentrations were measured in 107 uremic patients of 4 hemodialysis centers, in order to study the prevalence of hypothyroidism in hemodialysis patients. In accordance with the clinical impression there was no laboratory evidence of thyroid dysfunction. In spite of the fact that all patients had the expected low-T3 syndrome, there were highly significant differences between the mean thyroid hormone concentrations of the 4 different centers. The center with the highest thyroid hormone levels (all normal except for borderline low 3,5,3'-triiodothyronine) also had the lowest urea levels, indicating the relatively best metabolic control. One center had significantly lower hormone levels than the other 3 centers (all hormones except free thyroxine were below normal) with urea levels that did not differ significantly from one of these centers. A retrospective analysis of patients and of the techniques of dialysis of 3 centers excluded factors like heparin or the length of time on dialysis to be the reason for the low values of this center. Finally, only the significantly higher proportion of unsuccessfully transplanted patients and some technical differences (lack of water treatment, regenerated cellulose as dialyser membrane, and low magnesium content in the dialysate) unique for this center remained as possible factors that may speculatively explain the observed low thyroid hormone values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097561 TI - Evidence that opioid peptides and dopamine participate in the suckling-induced release of prolactin in the ewe. AB - A pharmacological approach was used to study the involvement of opioid peptides and dopamine in mediating the suckling-induced release of prolactin in the lactating ewe (10-20 days post partum). To promote reliable and predictable suckling activity lambs were fitted with elasticated masks to prevent sucking for 4.5 h. After a 1-hour control period of frequent blood sampling, ewes were treated (i.v. injections every 5 min) for a further 75 min with either saline vehicle, an opioid antagonist (naloxone; 4.17 mg/5 min), a dopamine antagonist (metoclopramide; 1.25 mg/5 min), a mixture of naloxone + metoclopramide or a dopamine agonist (apomorphine; 6.6 mg/5 min). Blood was withdrawn at 5-min intervals for determination of plasma prolactin and luteinizing hormone (LH) by radioimmunoassay. Plasma LH concentrations (less than or equal to 1 microgram/l) were not significantly affected by any of the drug treatments and there was no evidence for an acute fall in LH associated with suckling- or TRH-induced increases in prolactin secretion. Naloxone significantly (p less than 0.05) reduced the mean incremental change in prolactin concentration (delta PRL) in response to suckling (+7 +/- 18 micrograms/ml) compared with saline-infused controls (+79 +/- 26 micrograms/ml), an effect which was completely reversed by combined treatment with naloxone and metoclopramide (+146 +/- 56 micrograms/ml). Metoclopramide alone raised basal prolactin levels by 46% (p less than 0.01) but did not affect delta PRL in response to suckling (+115 +/- 52 micrograms/ml). Neither naloxone, metoclopramide nor a combination of the two drugs affected the subsequent prolactin to TRH (10 micrograms). Apomorphine, however, completely abolished both the suckling- and TRH-induced release of prolactin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097562 TI - Origin of septal thyrotropin-releasing hormone in the rat. AB - Through the combined demonstration of retrograde transport of horseradish peroxidase (HRP) and immunocytochemical staining of thyrotropin-releasing hormone (TRH), the TRH neurons that project to the lateral septum were identified. Following the injection of HRP into the lateral septum, retrogradely labelled neurons were detected in the bed nucleus of stria terminalis (BNST), the ventral pallidum, the anterior commissural nucleus, the lateral preoptic nucleus and the perifornical region. Some neurons in the BNST and the perifornical region were found to contain both TRH and HRP. In contrast, no TRH-containing neurons were labelled with HRP in the paraventricular nucleus, the putative thyrotropic area. These data suggest that TRH neurons projecting to the lateral septum were different from those which send fibers to the median eminence. PMID- 3097560 TI - Ca-controlled, reversible structural transition in myelin. AB - When excised goldfish spinal cord is kept in physiological saline at room temperature, the myelin multilayers swell. As studied by X-ray diffraction, the original repeating distance of 150 A (AS myelin) swells to 177 A (AL myelin); no intermediate distances are seen. At least 70% of the myelin can undergo this gradual conversion. Omitting glucose from the saline, or substituting 2-deoxy-D glucose for the glucose, or adding NaCN to the saline all promote conversion. Cooling retards the rate but does not prevent conversion. Omitting Ca does prevent conversion, however, and substituting Mg, Sr, or Ba for Ca also does so. Moreover, agents that increase the rate of conversion in Ca-containing saline by up to 5 fold (NaCN, colchicine, A23187) fail to convert myelin in Ca-free saline. We then converted AL myelin back to AS by withdrawing Ca. After converting in NaCN-containing saline, up to 3/4 of the AL myelin recompacts in Ca-free saline; however, none of the myelin recompacts if NaCN is present in the Ca-free saline. Little or no recompaction occurs after conversion in saline without NaCN. Based on our results, we suggest that the oligodendrocytes may maintain AS myelin in vivo by pumping Ca out of the myelin sheath. The myelin in a human PNS nerve has been induced to undergo a similar cycle of swelling and recompaction. PMID- 3097563 TI - Ontogeny of growth hormone-releasing factor in the rat hypothalamus. AB - Using immunohistochemical techniques, we have studied the ontogenetic development of growth hormone-releasing factor (GRF) immunoreactive structures in the rat hypothalamus. Frozen sections of rat hypothalami were stained by the avidin biotin complex (ABC) method using a specific antiserum against rat GRF. Immunoreactive GRF nerve terminals but not perikarya were first detected in rat fetuses on the 20th day of gestation in the external layer of the median eminence (ME). An increased number of immunoreactive nerve terminals in the ME were observed at 1 and 2 days of age. In addition, perikarya containing immunoreactive GRF-like material were observed in the arcuate nucleus (ARC). Rats at 5 days of age showed a further increase in GRF immunoreactive terminals, which now were also present in the internal layer of the ME. In 10- and 20-day-old rats immunoreactive nerve terminals were only moderately increased in the ME. GRF immunoreactive perikarya were observed in the ARC and also in proximity to the ventromedial nucleus. Moreover, GRF containing fibers were seen projecting from the ARC to the ME. Colchicine treatment of postnatal rats reduced immunostaining of the nerve animals in the ME, but did not affect that of the perikarya. These results are consistent with the view that the neural control of growth hormone secretion develops in the rat during late gestation and continues to mature during the early postnatal period. PMID- 3097564 TI - Further evidence that thyrotropin-releasing hormone participate in the regulation of growth hormone secretion in the rat. AB - Effects of thyrotropin-releasing hormone (TRH) on growth hormone (GH) secretion were investigated in vivo (on intact or mediobasal hypothalamic lesioned rats tested under either anesthesia or free moving conditions) as well as in vitro (in incubation or perifusion systems of anterior pituitary tissue). The peptide induced a rapid, dose-dependent increase of plasma GH levels in free moving animals bearing an extensive lesion of the mediobasal hypothalamus including the median eminence. Under comparable conditions, TRH was ineffective in intact animals. After chloral hydrate anesthesia a GH response to TRH was recorded in both groups, but lesioned rats exhibited a better responsiveness to all doses tested. In vitro TRH increased GH release from incubated or perifused pituitaries sampled from both intact and lesioned rats in a transient and concentration dependent manner. A similar effect was obtained with the (3 Me His2) analogue of TRH. These findings indicate that TRH can affect GH secretion at the pituitary level under specific experimental conditions and support the hypothesis that either peripheral hormones or other, still unidentified hypothalamic neurohormones may modulate this effect. PMID- 3097566 TI - Cerebrospinal fluid pulse pressure and the pulsatile variation in cerebral blood volume: an experimental study in dogs. AB - The cerebrospinal fluid pulse pressure (CSFPP) has found application as a measure of intracranial elastance. However, CSFPP is also dependent on the magnitude of the pulsatile variation in cerebral blood volume (delta Vb). The purpose of the present study was to assess the effect on delta Vb of changes in systemic arterial pressure (SAP) and arterial carbon dioxide tension (PaCO2) as well as elevation of intracranial pressure (ICP). Therefore, delta Vb was computed from the electromagnetically measured flow profile in the vertebral artery of the dog on the assumption of a nonpulsatile cerebral venous outflow. During arterial hypotension, delta Vb was increased due to a shift of flow from diastole to systole, whereas mean flow was not affected. The reverse phenomenon was observed when SAP was raised. Changes in PaCO2 had little effect on pulsatile blood flow. The changes in total blood flow that occurred were evenly distributed over the cardiac cycle. Consequently, delta Vb was not significantly affected, although CSFPP was considerably changed. When ICP was raised, a breakpoint pressure was observed above which cerebral blood flow (CBF) decreased and CSFPP and delta Vb increased. This contradiction was explained by the finding of a decrease in diastolic flow, causing the fall in CBF, whereas systolic flow relative to mean flow was increased, resulting in an increased delta Vb. The underlying mechanisms of the pulsatile flow changes are extensively discussed. It is argued that the arterial inflow profile is largely determined by the compliance of the inflow section of the cerebral vascular bed. Vascular compliance is significantly altered by changes in SAP and ICP because they affect the transmural pressure of the vessels, whereas this is not the case during changes in PaCO2. PMID- 3097565 TI - Interaction between estradiol and a nonsteroidal factor in porcine follicular fluid in regulating LH pulse amplitude between the mornings of diestrus 2 and proestrus in the rat. AB - The object of this study was to examine the effect of porcine follicular fluid (PFF) alone or in combination with estradiol (E2) on pulsatile LH release during the interval between the mornings of diestrus 2 (D2) and proestrus in the rat. Steroids were removed from PFF by charcoal extraction. Preliminary studies indicated that 1 ml PFF given intraperitoneally suppressed FSH secretion for up to 15 h, with an onset of action between 3 and 4 h and maximal suppression between 6 and 9 h. In subsequent experiments, six groups of animals were bled continuously for 3 h between 07.30 and 10.30 h at a rate of 50 microliter whole blood/5 min: group 1 was bled on D2; group 2 was sham ovariectomized on D2 (08.30 09.30 h), immediately implanted with an empty capsule, given saline at 12.00 and 24.00 h, and bled on proestrous AM; groups 3-6 were ovariectomized on D2, implanted with an empty or E2 capsule, given 1 ml saline or PFF at 12.00 and 24.00 h, and bled 24 h following ovariectomy (OVX). Between D2 and proestrus plasma E2 levels increased, and there was no change in any parameter of pulsatile LH release. However, OVX on D2 reduced plasma E2 levels and increased mean blood LH levels above proestrous values due to increases in LH pulse amplitude and frequency. Restoration of physiological proestrous levels of E2 reduced the increase in mean blood LH levels, by lowering pulse frequency to proestrous values and by greatly reducing pulse amplitude. However, LH pulse amplitude and mean blood LH levels were still higher than values on proestrus. PFF alone produced no alteration in any parameter of pulsatile LH release compared with saline-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097567 TI - Therapeutic efficacy of multiagent chemotherapy with drug delivery enhancement by blood-brain barrier modification in glioblastoma. AB - Reversible osmotic blood-brain barrier (BBB) modification was used in 38 patients with glioblastoma to enhance the delivery of chemotherapeutic agents. The patients ranged in age from 14 to 70 years (mean, 43), and all had prior surgery and radiation; 5 had also received systemic chemotherapy. Karnofsky Performance Status (KPS) scores ranged from 60 to 100% (mean, 79) on admission to the treatment program. Barrier modification was achieved by intracarotid or intravertebral artery infusion of mannitol, and a chemotherapy regimen of methotrexate, cytoxan, and procarbazine was given in conjunction with barrier modification. The 38 glioblastoma patients were compared to two control groups of patients with glioblastoma; these encompassed 14 patients treated with surgery and radiation and 8 treated with surgery, radiation, and systemic chemotherapy. Survival analysis using the Cox Proportional Hazards Regression Model (corrected for age, sex, presence or absence of necrosis, and functional status) showed that patients receiving chemotherapy with BBB modification had a statistically significant (P = 0.0006) longer expected survival (17.5 months) than the control groups (12.8 and 11.4 months, respectively). Presently 16 patients of the barrier enhanced treatment group are alive at 5 to 42 months from diagnosis (median, 20) with KPS scores ranging from 40 to 90% (median, 65). The neurological complications seen included a stroke-like syndrome in 3 patients (1 with decreased motor movement in the hand, 1 with marked hemiparesis, and 1 with hemiplegia), transient exacerbation of preexisting neurological deficits lasting 2 to 3 days, and a 15% incidence of seizures during or within 24 hours of the BBB modification. In 2 of the 38 patients, radiographic documentation of central nervous system tumor regression concurrent with the development of new tumor nodule(s) in portions of the brain distant from the region of osmotic BBB opening was seen. These studies indicate that chemotherapeutic drug delivery to tumors (as well as surrounding brain) can be augmented by osmotic BBB modification and that such therapy can result in a prolongation of survival. PMID- 3097568 TI - Cruciate paralysis. PMID- 3097569 TI - Technique of experimental aneurysm formation in the rat common carotid artery using the milliwatt carbon dioxide laser and the adventitia patch model. AB - Aneurysms were induced in the rat common carotid artery by using the milliwatt carbon dioxide laser to weld an adventitia patch over a hole. This technique proved to be effective and reliable as demonstrated by the 100% incidence of aneurysm formation at the patch site in 28 rats killed 1 week or later after the procedure. It is suggested that this technique may be used to produce intracranial aneurysms in experimental animals due to the minimal vessel manipulation required. PMID- 3097570 TI - Neuropeptide therapies in chronic schizophrenia: TRH and vasopressin administration. AB - Twenty-three chronic undifferentiated schizophrenics, 13 women and 10 men, aged 37-64 years with 15-to 40-year histories of the disease were given either thyrotropin-releasing hormone (TRH) (10 subjects) or DDAVP (13 subjects) with the aim to improve the negative symptoms of the disease and memory. TRH (600 micrograms i.v.) and DDAVP (4 micrograms i.m.) were administered every other day for 30 days. Negative symptoms were monitored by the Andreasen rating scale and by the Honingfeld NOSIE rating scale, memory by the Folstein 'Mini mental State' rating scale and by the Luria-Nebraska rating scale before therapy and then at days 15, 16, 30 and 31 of treatment. Both therapies significantly improved negative symptoms. Memory was significantly improved in all the patients treated with TRH and in 9 of the 13 patients treated with DDAVP, who presented less severe cognitive impairments. A peripheral mechanism of action of DDAVP was excluded by the observation that plasma electrolytes and osmolality, blood pressure, ECG patterns, 24-hour urine volume and specific gravity, basal plasma cortisol and growth hormone levels and weight of the patients were unchanged during therapy. TRH treatment induced a transient borderline hyperthyroidism at day 15 and a progressive decrease of the thyrotropin response to TRH stimulation. A common mechanism of action of the two peptides on the central noradrenergic system is suggested. PMID- 3097571 TI - Aids. Case for diagnosis. PMID- 3097573 TI - Microbiologic assessment of drinking water potability during brigade operations. PMID- 3097572 TI - Malacoplakia of the colon. PMID- 3097574 TI - Non-adaptability to basic training and the Millon Clinical Multiaxial Inventory. PMID- 3097575 TI - A unique training opportunity: medical care as a joint venture between a health services command community hospital and a forces command evacuation hospital. PMID- 3097577 TI - Utilization of psychiatric consultation with an elderly medically ill inpatient population in a VA hospital. PMID- 3097576 TI - Integration of military unit and civilian hospital during mass casualty situation: experience during the 1982 Lebanon War. PMID- 3097578 TI - The diagnosis and treatment of psychiatric disorders in medically ill patients. PMID- 3097579 TI - The mandibular staple bone plate: long term evaluation of 40 cases. PMID- 3097581 TI - Magnetic resonance scan of an encephalomalacic brain lesion due to concussive shrapnel wound. PMID- 3097580 TI - Hourglass gallbladder: an update. PMID- 3097582 TI - Traumatic diaphragmatic rupture: a five year experience at William Beaumont Army Medical Center. PMID- 3097583 TI - Carotid endarterectomies at Walter Reed Army Medical Center: morbidity and mortality, 1982-1983. PMID- 3097584 TI - Periappendicitis: possible surgical pitfall. PMID- 3097585 TI - Case for diagnosis. Nasal cavity hemangiopericytoma. PMID- 3097586 TI - Seizure disorder warning. PMID- 3097587 TI - [Initial approach to the injured patient]. PMID- 3097588 TI - [Gastric diverticuli. A statistical contribution]. PMID- 3097589 TI - Demonstration of monoamine oxidase type B in serotonergic and type A in noradrenergic neurons in the cat dorsal pontine tegmentum by an improved histochemical technique. AB - Application of a diaminobenzidine-coupled peroxidation method to monoamine oxidase (MAO) histochemistry demonstrates a detailed morphology of MAO-containing perikarya, dendrites, axons and fibers in the dorsal pontine tegmentum of the cat, sectioned with a vibratome. Further, utilization of specific inhibitors, deprenyl and clorgyline, also provides evidence that serotonergic neurons contain exclusively MAO-B and catecholaminergic ones contain MAO-A. PMID- 3097590 TI - Thyrotropin-releasing hormone (TRH) degradation in NIH:N mouse cerebral cortex and spinal cord. AB - Thyrotropin-releasing hormone (TRH) metabolism in NIH:N mouse cerebral cortex and spinal cord was studied with high pressure liquid chromatography. Degradation of added TRH was significantly (P less than 0.001) slower in the spinal cord (2.19 +/- 0.46%/min) than in the cerebral cortex (7.54 +/- 0.31%/min). Bacitracin, a non-competitive inhibitor of TRH deamidase, inhibited TRH degradation by 61.3 +/- 3.7% in the spinal cord but only by 35.9 +/- 1.0% in the cerebral cortex (P less than 0.001). Catabolism of TRH in the mouse spinal cord proceeds at a slower rate and predominantly via the TRH deamidase pathway. PMID- 3097591 TI - Polyamines as intermediates in developmental neurotoxic events. PMID- 3097592 TI - Methotrexate, folate and the brain. PMID- 3097593 TI - Valproate-induced accumulation of gamma-aminobutyric acid after chronic exposure to inorganic lead. PMID- 3097594 TI - Effects of feeding in burn injury. PMID- 3097595 TI - Combined EFA deficiency in a patient on long-term TPN. PMID- 3097596 TI - Feeding the flame. PMID- 3097597 TI - Acrofacial dysostosis of Nager and ocular abnormalities. AB - Acrofacial dysostosis of Nager is a little known hereditary syndrome in which the findings of mandibulofacial dysostosis are associated with defects of the limbs. The present case showed other abnormalities including the Stilling-Turk-Duane syndrome, conductive deafness and ptosis of the transverse colon. PMID- 3097598 TI - Aniridia, atypical iris defects, optic pit and the morning glory disc anomaly in a family. AB - A two-month-old girl with aniridia was found to have an optic pit in one eye and the morning glory disc anomaly in the other eye. The patient's mother had corectopia and atypical iris defects. The findings are described and the embryology of the various abnormalities briefly reviewed. This is the first report of such an association of findings in a family with aniridia. Failure of normal neuroectodermal development may play a role in the development of optic pits and the morning glory disc anomaly. PMID- 3097599 TI - Re: Seckel's syndrome with pseudopolycoria. PMID- 3097600 TI - IRRC approves long-term care regulations. PMID- 3097601 TI - Acquired resistance of black mollies Poecilia latipinna to infection by Ichthyophthirius multifiliis. AB - Changes in the response of black mollies Poecilia latipinna to infection with Ichthyophthirius multifiliis subsequent to single I. multifiliis infections were examined experimentally. Incomplete resistance to infection was established, the degree of which did not depend on the intensity of the initial infection. Resistance was maintained for longer periods, however, by those fish with higher initial levels of infection. Previous experience of infection by their hosts had a significant, though small, effect on the time for which trophozoites remained on the fish. The influence of these results on the population dynamics of the Ichthyophthirius-fish interaction is examined with the aid of simple mathematical models. PMID- 3097602 TI - Linked metabolism of L-serine and L-alanine by Moniliformis moniliformis (Acanthocephala) in vitro. AB - Experiments to investigate the linked metabolism of L-serine and L-alanine by Moniliformis moniliformis in vitro were carried out by incubating adult worms aerobically for 3 h at 37 degrees C in Tyrode's solution containing L-[U 14C]alanine and other amino acids. When present in the medium alone, alanine was totally removed by the worms and metabolized almost entirely to ethanol and a compound identified as carbon dioxide. When present in the medium with serine and no other amino acids, alanine was largely metabolized as before but additional alanine, believed to originate from serine, was excreted. The same results were obtained with serine and 16 other amino acids in the incubation medium. PMID- 3097603 TI - [Maxillo-facial trauma in sports]. PMID- 3097604 TI - [Occlusion according to the Tweed school]. PMID- 3097605 TI - [Reconstruction with a dentin adhesive using the original fracture fragment]. PMID- 3097606 TI - [Current possibilities and limits in periodontal diagnosis]. PMID- 3097607 TI - [Disinfection of the dental office in relation to environment and furnishings]. PMID- 3097608 TI - [Prevention in the dental office: disinfection and sterilization of instruments]. PMID- 3097609 TI - [Ultrastructure of leukoplastic lesions: tonofilaments]. PMID- 3097610 TI - [Clinico-statistical study of apical periodontopathy]. PMID- 3097611 TI - [The curve of Spee in Tweed's occlusion]. PMID- 3097612 TI - [The use of a simple functional regulator in interceptive orthodontic therapy]. PMID- 3097613 TI - [Anchorage preparation in edgewise technic according to the Tweed school]. PMID- 3097614 TI - [The Jarabak method of growth prediction. Diagnostic considerations and therapeutic implications]. PMID- 3097615 TI - [Synthesis of epidemiological data on carcinoma of the mouth]. PMID- 3097616 TI - Identification of interference affecting the gas-liquid chromatography analysis of valproic acid in quality control material. AB - The matrix used to prepare control material for the Chemical Pathology Quality Assurance Programme Group of the Royal College of Pathologists of Australasia/Australian Association of Clinical Biochemists (RCPA/AACB) was investigated to identify a contaminant affecting the gas-liquid chromatography (GLC) analysis of valproic acid (VPA). The contaminant, not present in patients' sera, eluted with the octanoic acid internal standard in our GLC procedure. The compound was identified as octanoic acid. The source of this contamination could not be determined. The presence of endogenous octanoic acid in the RCPA/AACB quality control material precluded the use of octanoic acid as an internal standard. PMID- 3097617 TI - Ontogenic development of gastrointestinal motility: IV. Duodenal contractions in preterm infants. AB - Duodenal motility was studied by intraluminal manometry in 27 healthy infants of 26 to 42 weeks, gestational age. The frequency of contractions, the number of contractions per burst, and the intraluminal peak pressure during contractions all increased during a narrow postconceptual period, 29 to 32 weeks, regardless of length of gestation before birth. Antenatal beta-methasone administration to the mothers of 11 additional infants of 26 to 32 weeks gestational age was associated with increased duodenal contraction rate, number of contractions per burst, and intraluminal peak pressure compared with infants of similar gestational age whose mothers did not receive beta-methasone. The maturational effect of beta-methasone on duodenal motility was most pronounced in infants whose gestational age at birth was 26 to 29 weeks. Seven infants of 31 weeks' or longer gestational duration who had a CNS abnormality or insult had fasting duodenal contraction rates that were less than one half of the rate for normal infants of similar gestational age. These observations suggest that neonatal duodenal motility undergoes marked maturational changes between 29 and 32 weeks after conception and that these changes may be inducible before 29 weeks by corticosteroid administration. An intact CNS appears to be required for full expression of the maturational changes. PMID- 3097618 TI - Familial partial peripheral and pituitary resistance to thyroid hormone: a frequently missed diagnosis? AB - The diagnosis of partial peripheral and pituitary resistance to thyroid hormone was ultimately made in two boys, 7 and 9 years of age, and a 10-year-old girl who had goiters and hyperthyroxinemia. The boys were treated with propythiouracil and/or thyroidectomy or iodine 131 for suspected thyrotoxicosis but had poorly suppressible serum thyroid-stimulating hormone (TSH) post treatment in spite of the usual L-thyroxine replacement. The girl had increasing goiter size while receiving propylthiouracil, 100 mg every eight hours. These findings led to reevaluation of thyroid hormone dynamics in these children and their families. Twelve additional family members, 3 to 38 years of age, compatible with an autosomal dominant inheritance, were also found to have peripheral and pituitary resistance to thyroid hormone. All affected individuals had elevated serum thyroxine and triiodothyronine levels, normal to slightly elevated triiodothyronine resin uptakes, and a nonsuppressed serum TSH. The five individuals who were given thyrotropin-releasing hormone showed exaggerated TSH responses, which normalized on L-thyroxine therapy. Misdiagnosis in six of 15 family members led to significant morbidity (hypothyroidism, delayed growth, and therapy risk). A nonsuppressed serum TSH in a patient with suspected thyrotoxicosis should lead to suspicion of this disorder. Appropriate management for this condition includes L-thyroxine therapy to decrease goiter size and normalize TSH responses to thyrotropin-releasing hormone. PMID- 3097619 TI - Effect of exogenous dopamine on the hypercapnic ventilatory response in cats during normoxia. AB - The effects of exogenous dopamine on the normoxic hypercapnic ventilatory response were assessed in nine chloralose-urethane anesthetized cats using the technique of dynamic end-tidal forcing. The ventilatory responses to step changes in end-tidal PCO2 (PETCO2) were measured before (control), during and after intravenous infusion of dopamine (420 micrograms X kg-1 X h-1). Each response was separated into a slow central and a fast peripheral chemoreflex loop by fitting two exponential functions to the measured ventilation. Both loops were described by a CO2 sensitivity, time constant, time delay and a single off-set B (extrapolated PETCO2 of the steady-state response curve at zero ventilation). Dopamine infusion only caused a significant increase of B (mean 0.3 kPa, P less than 0.0001) compared to control; the other model parameters were not significantly affected. After dopamine infusion B returned to significantly lower values (mean 0.2 kPa, P = 0.006) than in control. In two additional cats the dopamine administered to the blood which was artificially perfusing the brainstem, did not affect ventilation. We conclude that in normoxic cats the effect of exogenous dopamine on the ventilatory response to CO2 is due to a CO2 independent inhibition of the ventilatory drive which originates outside the brainstem. PMID- 3097620 TI - Deletion polymorphism 5' to the human apolipoprotein AI (apo AI) gene. PMID- 3097621 TI - [Preliminary evaluation of post-radiation changes in patients with breast cancer after postoperative electron beam radiotherapy]. PMID- 3097622 TI - Rehabilitation and long-term management of the spinal cord injured adult. AB - Rehabilitation and long-term care of the spinal cord injured adult must be oriented toward prevention, be patient and family centered, and transcend all geographic settings. The nurse is a key coordinator and provider of care, as well as a facilitator of patient adaptation. The nurse involved in the care of the spinal cord injured adult must be knowledgeable in the rehabilitation and long term care considerations essential to the reintegration and well-being of this population. PMID- 3097623 TI - [GM 1 gangliosidosis. Description of a clinical case]. PMID- 3097625 TI - Emergency department management of children with acute isoniazid poisoning. AB - We suggest that the following therapeutic regimen be followed in cases of isoniazid poisoning in children. In cases of intractable seizure activity in a child which remains unexplained, consider isoniazid poisoning. Give pyridoxine as an intravenous bolus to all children in whom isoniazid toxicity is suspected, who exhibit seizure activity and are known to have been exposed to isoniazid, or who have a history of ingesting one gram or more of isoniazid. It should be given on a gram-for-gram basis, and the clinician need not await serum isoniazid levels before administering pyridoxine. It can be safely given at a rate of five grams per three minutes in a 50 ml volume. In fact, serum isoniazid determinations are not available in many emergency departments and have not been shown to correlate closely with symptomatology. When available, serum isoniazid levels at best are subject to variability owing to sampling procedures (serum protein must be removed within two hours of sampling). The result is that serum isoniazid levels play only a minor role in the emergency department management of isoniazid poisoning. To potentiate the antidotal effects of pyridoxine, diazepam (0.1 mg/kg) may be given intravenously, preferably at a second intravenous site. Because the lactic acidosis seen after seizures resolves spontaneously, and because metabolic alkalosis may result following excess lactate loading, administration of bicarbonate is usually not necessary, and may be harmful in some cases. After pyridoxine treatment, syrup of ipecac may be given to empty the stomach.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097624 TI - [Care of the newborn infant with respiratory distress syndrome using continuous negative pressure. 5 years' experience]. AB - Continuous Negative Pressure (CNP) was utilized as sole form of respiratory assistance in the treatment of 40 newborn infants with Respiratory Distress Syndrome (RDS). The average duration of CNP therapy was less than 7 days in all cases. 38 of these infants survived without sequelae (95%); an infant developed severe bronchopulmonary dysplasia (2.5%); another infant died from intracranial hemorrhage (2.5%). CNP appears to be an effective respiratory support in the treatment of neonatal RDS, when used early in spontaneously breathing infants weighing greater than 1500 grams. PMID- 3097626 TI - Early prognostic indicators in acute meningococcemia: implications for management. AB - Three pediatric patients presenting with fever and petechiae with unexpected rapid development of shock are reported. Clinical and laboratory parameters which may identify patients at risk for rapid deterioration are presented. The pathophysiology of meningococcal disease is discussed with emphasis on the possible implications in management. Patients identified at increased risk should be monitored closely; cardiovascular decompensation should be treated aggressively with fluids, pressors, and steroids in an attempt to reverse this process. PMID- 3097627 TI - [Antibacterial activity of beta-lactamase inhibitors and selected beta-lactam antibiotics]. PMID- 3097629 TI - [Clinical aspects of a single established isolation of mycobacteria]. PMID- 3097628 TI - Involvement of prostate in the regulation of serum levels of FSH, LH, and prolactin in male rats. AB - Circulatory levels of LH and FSH were measured in serum of male rats (28, 35, 42, 63, 70, 77, and 207 days of age) 7 days following sham operation, castration (C), prostatectomy (P), and castration + prostatectomy (C + P). In C + P rats that were 49, 63, 70, 77, and 207 days of age, the plasma FSH was significantly elevated as compared to the C group. Administration of aqueous prostatic extract restored the circulatory FSH level in C + P animals to that observed in C animals, whereas in C animals FSH levels were suppressed, indicating inhibinlike activity. In rats 49 and 77 days of age, circulatory LH levels were significantly suppressed in C + P animals as compared to the C group. Both castration and prostatectomy alone suppressed circulatory prolactin levels. Administration of prostatic extract to castrated animals restored the prolactin levels to that of the sham-operated control animals. Results of the present study suggest a role of the prostate in feedback regulation of FSH and prolactin. PMID- 3097630 TI - [Clinical significance of finding mycobacterial L forms in patients with destructive pulmonary tuberculosis]. PMID- 3097631 TI - [Diagnostic significance of isolating Mycobacterium tuberculosis L forms in patients at the sanatorium stage of treatment]. PMID- 3097632 TI - [Effect of rifampicin on the L transformation of a mycobacterial population in patients with destructive pulmonary tuberculosis]. PMID- 3097633 TI - [Cultivation of Mycobacterium tuberculosis and opportunistic mycobacteria on a medium with N-alkanes]. PMID- 3097634 TI - [Changes in the biological properties of Mycobacterium tuberculosis as affected by x-ray radiation]. PMID- 3097635 TI - [Epidemiologic and diagnostic significance of isolating bacteria from persons at risk for tuberculosis]. PMID- 3097636 TI - [Current concepts of the ultrastructure and function of the cell wall in Mycobacterium tuberculosis]. PMID- 3097637 TI - A GTP-binding protein of Escherichia coli has homology to yeast RAS proteins. AB - The DNA sequence of a gene (era) located immediately downstream of the gene (rnc) encoding ribonuclease III of Escherichia coli was determined and found to encode a protein of 316 amino acid residues. The amino acid sequence of this protein, Era, has significant similarity to the yeast RAS proteins. Overexpression of the Era protein was achieved and GTP cross-linking experiments demonstrated that the protein was indeed capable of binding GTP, as are the yeast and mammalian ras gene products. These data indicate that ras-related sequences occur not only in eukaryotes but also in prokaryotes. PMID- 3097638 TI - Regulated production of mu m and mu s mRNA requires linkage of the poly(A) addition sites and is dependent on the length of the mu s-mu m intron. AB - mRNAs encoding the membrane-associated (mu m) and secreted (mu s) forms of mu heavy chain are derived from transcripts of the same immunoglobulin gene by differential RNA processing. To help elucidate the mechanism that regulates the production of these two mu mRNAs during the course of B-lymphoid maturation, we produced a series of specifically modified mu-chain genes and studied their expression when transfected into cells representing either early or late developmental stages. We have established that proper regulation depends on linkage of the mu s and mu m poly(A) addition sites and the length of the mu s-mu m intron. Deletion of an 800 to 900-nucleotide segment from the central region of this intron abolishes regulation; replacement of this segment with miscellaneous DNA sequences restores it. From these results we propose a model in which regulation is principally achieved by competition between cleavage/polyadenylylation of the mu s site and splicing of the C mu 4 and mu m exons. PMID- 3097639 TI - Molecular cloning and chromosomal localization of human 4-beta galactosyltransferase. AB - A cDNA clone to human 4-beta-galactosyltransferase (EC 2.4.1.38) was isolated from a human liver lambda gt11 expression library by using a monospecific polyclonal antiserum to affinity-purified bovine enzyme. The authenticity of this cDNA clone has been demonstrated by several criteria. Under conditions of chronic treatment with the beta-adrenergic receptor agonist isoproterenol, rat parotid glands show an approximately 10-fold increase in 4-beta-galactosyltransferase activity. The increased enzyme activity was reflected in dot-blot analysis of control and isoproterenol-treated rat parotid RNA by using the human cDNA as probe. Hybrid-selection and in vitro translation identified a protein product with a molecular mass of 47 kDa that was immunoprecipitated with the bovine antiserum. The full-length human cDNA clone was then isolated and the DNA sequence for the NH2-terminal portion of the protein was deduced. Comparison of the NH2-terminal protein sequence from the bovine protein with that of the human cDNA clone confirmed its identity. In addition, the human cDNA clone was used to localize the gene for 4-beta-galactosyltransferase to human chromosome 4 by Southern analysis of a somatic cell hybrid panel. PMID- 3097641 TI - Rates of nucleotide substitution in Drosophila mitochondrial DNA and nuclear DNA are similar. AB - While the majority of DNA in eukaryotes is in the nucleus, a small but functionally significant amount is found in organelles such as chloroplasts and mitochondria. A recent, rather remarkable, finding has been that in vertebrates the DNA in the mitochondria (mtDNA) is evolving 5-10 times faster than the DNA in the nucleus. No similar studies have been done with invertebrates. Using the technique of DNA X DNA hybridization, we have measured the degree of nucleotide substitution between Drosophila melanogaster and Drosophila yakuba for both single-copy nuclear DNA (scnDNA) and mtDNA. The change in melting temperature is the same in both types of DNA hybrids. Thus we conclude that mtDNA and scnDNA are evolving at similar rates in these Drosophila. Considerable DNA sequence data are available for the mtDNAs studied, allowing us to estimate that a 1 degree C change in melting temperature corresponds to a 1.5-2% base-pair mismatch. PMID- 3097640 TI - Molecular basis for two different affinity states of the interleukin 2 receptor: affinity conversion model. AB - Two affinity species of the interleukin 2 (IL-2) receptor are different states of a single receptor molecule. We assumed that a binary complex between the IL-2 receptor and another lymphocyte-specific protein would constitute the high affinity receptor. To test this assumption, we counted the numbers of IL-2 receptors with high and low affinity in a murine T-cell line CT/hR-1 that expresses not only murine but also human receptors by cDNA transfection. We found that human high-affinity receptors disappeared when the murine high-affinity receptors were already occupied by the ligand. The results were incompatible with a fixed number of human and murine receptors with high affinity in CT/hR-1 cells. We suggest that the high-affinity state of the IL-2 receptor is a ternary complex of IL-2, the IL-2 receptor, and a postulated "converter" protein, which is fewer in number than the receptors. The converter would be unable to form a complex with the IL-2 receptor unless IL-2 was already bound to it. The ligand binding to the receptor would cause a conformational change in the receptor, increasing its affinity to the converter. Ternary complex formation would, in turn, change the apparent affinity of the receptor to the ligand from low to high by reduction of the dissociation constant. PMID- 3097642 TI - Interferon-gamma regulates an antigen specific for endothelial cells involved in lymphocyte traffic. AB - One of the most striking examples of localized vascular differentiation is exhibited by specialized lymphoid organ venules that mediate the extravasation of circulating lymphocytes from the blood. These vessels are characterized by cuboidal or "high" endothelial cell morphology and are unique in their functional capacity to interact with migrating lymphocytes, regulating both the rate and specificity of lymphocyte traffic through particular regions of the body. We describe here a monoclonal antibody, MECA-325, that defines an endothelial cell differentiation antigen selectively expressed on high endothelium in the mouse. Thus an antigen defining a specific functional subset of endothelial cells has been found. Furthermore, we demonstrate that the MECA-325 antigen can be induced in mouse lung or bone marrow-derived endothelial cell lines in vitro by interferon-gamma but not by interferon-beta, interleukin-1, or endothelial cell mitogens. The results define a unique marker associated with differentiated endothelial cells mediating lymphocyte traffic from the blood, and they provide evidence that the specialized phenotype of these high endothelial cells may be induced and controlled by local factors associated with immune activity. PMID- 3097643 TI - Structural differences in a single gene encoding the V kappa Ser group of light chains explain the existence of two mouse light-chain genetic markers. AB - Two phenotypic markers of mouse immunoglobulin kappa light chains, the IB-peptide marker and the Ef1a isoelectric focusing marker, are expressed by the C58/J, AKR/J, RF/J, and PL/J strains (called expressor strains) but not by BALB/c and most inbred strains. Expression is linked to the kappa light-chain locus and the Lyt-2/Lyt-3 genes on chromosome 6. Light chains bearing these markers belong to a group of variable region kappa chain (V kappa) regions called V kappa Ser, which has a serine amino terminus and a framework 1 region not observed to date among BALB/c light chains. Southern hybridization of genomic DNA with a V kappa Ser specific cDNA probe has demonstrated a single strongly hybridizing DNA fragment in all strains of mice tested. Characteristic restriction enzyme polymorphisms define the V kappa Ser alleles of expressor (Igk-VSera) and nonexpressor (Igk VSerb) strains. In the present study, the unrearranged V kappa Ser gene and its flanking regions from an expressor (C.C58) and nonexpressor (BALB/c) strain have been cloned and their nucleotide sequences determined. The C.C58 V kappa Ser gene isolated (the Igk-VSera allele) was shown to code for the two phenotypic markers described. While the nucleotide sequence of the BALB/c coding region (the Igk VSerb allele) shows 97% identity with the C.C58 gene, single nucleotide substitutions lead to structural changes in the encoded protein which render it IB-negative and Ef1a-negative. These differences alone can explain the failure of strains containing the BALB/c allele to express these kappa-chain phenotypic markers. Also, the BALB/c gene contains a single substitution in a conserved octamer sequence approximately equal to 100 nucleotides upstream of the coding region, which could affect its expression. Finally, the C.C58 allele contains a BAM5/R repetitive DNA element approximately equal to 1200 nucleotides upstream of the coding regions that is not present in BALB/c. This element gives rise to the EcoRI and BamHI restriction enzyme polymorphisms, which distinguish the Igk-VSera and Igk-VSerb alleles. PMID- 3097645 TI - Isolation of CD1 genes: a family of major histocompatibility complex-related differentiation antigens. AB - CD1 differentiation antigens are defined by a group of monoclonal antibodies that characterize immature human thymocytes. A cloned cDNA has been used to identify CD1 genes in a human genomic library. Five CD1 genes have been isolated, and Southern blot analysis suggests that these represent all the cross-hybridizing human CD1 genes. They share a highly conserved exon, which is homologous to the beta 2-microglobulin-binding domain (alpha 3) of major histocompatibility complex (MHC) class I antigens. In this domain, amino acid sequences are 71-88% homologous. However, the homology between CD1 and MHC class I alpha 3 domains is only 21%. This is the same degree of homology as between either of them and the class II beta 2 domain, which does not bind beta 2-microglobulin. The evolutionary implications of these results are discussed. PMID- 3097644 TI - Regulation of a transfected human class II major histocompatibility complex gene in human fibroblasts. AB - To investigate the cis-acting DNA elements that are involved in regulation of class II major histocompatibility complex genes, including gamma-interferon (gamma-IFN) induction, 5' flanking DNA deletions of a DQ beta "minigene" were analyzed in stable transfected cell lines. At least four elements 5' to the gene were found to be involved in DQ beta regulation. Deletion of sequences from -2500 to -159 base pairs (bp) resulted in increased transcription, suggesting that negative regulatory elements resided in the deleted region. These clones were all capable of responding to gamma-IFN. Further deletion of sequences from -159 to 128 bp resulted in constitutive high level transcription and the inability of these constructions to respond to gamma-IFN. A deletion to -107 bp resulted in a decrease in the basal level of expression that was restored by removal of the 5' DNA sequence to -82 bp, suggesting the presence of a second negative element. Finally, deletion to -64 bp caused a marked decrease in expression, suggesting the loss of an element necessary for high levels of transcription. The gamma-IFN control and the transcription control elements contain the conserved upstream sequences found in all class II genes, suggesting a role for these sequences. PMID- 3097646 TI - Specific human cytotoxic T cells recognize B-cell lines persistently infected with respiratory syncytial virus. AB - The T-lymphocyte response to respiratory syncytial (RS) virus has been invoked to explain the bronchiolitis and pneumonia caused by RS virus in human infants. However, T cells also appear to play a role in protection against RS virus infection. Although RS virus-specific human lymphocytes have been demonstrated, neither the phenotype nor the function of the lymphocytes was characterized. We describe here the induction of anti-RS virus cytotoxic T lymphocytes, in both bulk culture and restimulated cell lines, from human peripheral blood. Infection of Epstein-Barr virus-transformed human B-cell lines with RS virus in vitro readily caused a persistent infection; these cells continued to synthesize RS viral proteins and secrete infectious RS virus 4 months after infection. The persistently infected cells were used both to restimulate cytotoxic-T-cell precursors and as targets for RS virus-specific cytotoxic T cells. PMID- 3097647 TI - Pathological regulation of arachidonic acid release in cystic fibrosis: the putative basic defect. AB - The regulation of arachidonic acid release from membrane phospholipids was investigated in lymphocytes from patients with cystic fibrosis as well as control patients. No effect of either dexamethasone or fetal calf serum was seen on arachidonic acid release from cystic fibrosis lymphocytes, in contrast to control lymphocytes. In the latter cells, arachidonic acid release was inhibited by dexamethasone, fetal calf serum, or both. There were no differences in glucocorticoid receptor in lymphocytes from the two groups with regard to Kd and number of binding sites per cell. Furthermore, dexamethasone inhibited the incorporation of thymidine into lymphocytes from either group, indicating a normal functional glucocorticoid receptor. The defective regulation of arachidonic acid, resulting in an increased turnover, can explain many of the findings in cystic fibrosis, and we hypothesize that it is the basic defect causing the disease. The defect occurs at a level after the glucocorticoid receptor, which is functionally normal, and involves either the glucocorticoid dependent phospholipase-inhibitory protein lipomodulin (lipocortin) or phospholipase A2. PMID- 3097648 TI - Interleukin 2 mediates the inhibition of oligodendrocyte progenitor cell proliferation in vitro. AB - In the immune system, T-lymphocyte proliferation depends on interleukin 2 [IL-2 (T-cell growth factor)] interaction with specific receptors. In this study we show that IL-2 can specifically inhibit the proliferation of neonatal rat oligodendrocyte progenitor cells cultured in a serumless, chemically defined medium (oligodendrocyte-defined medium; ODM). IL-2 inhibited both [3H]thymidine incorporation and increase in cell number. Specificity was shown by precipitating IL-2 activity with anti-IL-2 antiserum. Furthermore, growth inhibition depended on the expression of Tac (an anti-IL-2 receptor monoclonal antibody)-positive receptors (IL-2 receptor). When cells were cultured in the presence of IL-2, both Tac-positive staining and growth inhibition were no longer expressed. The addition of interleukin 1 had no effect on [3H]thymidine incorporation or changes in cell number. However, when IL-1 was subsequently added together with IL-2, Tac expression and IL-2-mediated inhibition of cell proliferation was induced. This inhibitory effect was not due to a sensitive subpopulation because greater than 90% of the culture was Tac positive. Taken together, these data show that IL-2 can specifically inhibit oligodendrocyte proliferation and acts via Tac-positive receptors. PMID- 3097651 TI - Chemically-induced mammary gland tumors in rats: modulation by dietary fat. PMID- 3097649 TI - Octapeptides deduced from the neuropeptide receptor-like pattern of antigen T4 in brain potently inhibit human immunodeficiency virus receptor binding and T-cell infectivity. AB - The differentiation antigen T4, present on the helper/inducer subset of T lymphocytes, is thought to serve as the receptor for the human immunodeficiency virus (HIV). We find that a 60-kDa protein, immunoprecipitable by monoclonal antibody (mAb) OKT4, is present on membranes from human brain as well as human T cells. Furthermore, the radioiodinated HIV envelope glycoprotein [125I-labeled gp120 (125I-gp120)] can be specifically covalently affixed to a molecule present on rat, monkey, and human brain membranes to yield a complex that is indistinguishable from that formed on human T cells. T4 antigen has been studied on unfixed squirrel monkey, rat, and human brain sections by autoradiography using the mAb OKT4. A highly conserved neuroanatomical pattern has been demonstrated, suggesting an analogous organization in these three mammalian brains. Furthermore, the localization of 125I-gp120 receptor binding appears similar to that of T4 and is highly reminiscent of patterns for many previously characterized neuropeptide receptors. A computer-assisted analysis of gp120 suggested that a previously unremarkable octapeptide sequence within the gp120 protein, which we have synthesized and termed "peptide T," may play an important role in HIV attachment. Thus, peptide T and three rationally designed peptide analogs, each with a systematic amino acid substitution, potently inhibit specific 125I-gp120 binding to brain membranes. Additionally, when tested in a viral infectivity assay, these peptides show the same rank order and similar absolute potency to block HIV infection of human T cells. Thus, peptide T may provide a useful pharmacological or immunological basis for the control and treatment of AIDS. PMID- 3097650 TI - Modulation of gamma-aminobutyric acid-mediated inhibitory synaptic currents in dissociated cortical cell cultures. AB - Inhibitory gamma-aminobutyric acid-mediated synaptic currents were studied in dissociated primary cultures of neonatal rat cortex with the whole-cell patch clamp technique. Immunocytochemical staining of the cultures showed the presence of a large number of glutamic acid decarboxylase-containing neurons, and electrical stimulation of randomly selected neurons produced in many cases chloride-mediated and bicuculline-sensitive inhibitory synaptic currents in postsynaptic cells. The amplitude and decay time of the inhibitory synaptic currents were increased by flunitrazepam and decreased by the beta-carboline derivative methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, two high affinity ligands for the allosteric regulatory sites of gamma-aminobutyric acid receptors. The imidazobenzodiazepine Ro 15-1788, another high-affinity ligand of the gamma-aminobutyric acid receptor regulatory sites that has negligible intrinsic activity, blocked the action of flunitrazepam and beta-carboline. However, Ro 15-1788 also increased the decay rate of the inhibitory synaptic currents. This might suggest that an endogenous ligand for the benzodiazepine beta-carboline binding site is operative in gamma-aminobutyric acid-mediated synaptic transmission. PMID- 3097652 TI - Relevance of trans fatty acids and fish oil in animal tumorigenesis studies. PMID- 3097653 TI - Oil gavage test-compound administration effects in NTP carcinogenesis-toxicity testing. AB - Consulting toxicologists began in 1982 to question the use and potential involvement of oil gavage test-compound administration in unexpected NTP carcinogenesis responses. Investigations have focused on corn oil gavage alternatives, vehicle type and volume, alteration of MTD, teratogenic effects, disposition of test compounds, and target tissues. Micoencapsulation will require considerable development research to make it a suitable alternative. Vehicle type and volume appear to have different effects on the apparent MTD, teratogenicity and disposition of very similar compounds. Only two tissue effects have been observed in the NTP oil gavage bioassay data. First, there is a sporadic and weak association with exocrine pancreatic acinar cell proliferative lesions; these lesions are highly correlated with overweight male Fischer 344/N rats. Second, leukemia is reduced about 50 percent in the male Fischer 344/N rats; this is a strong association which results in an 8-10 percent increase in survival. The protective effect of corn oil gavage is remarkable and there is no significant enhancement of tumor development. Corn oil gavage under the conditions of the NTP carcinogenesis bioassay does contribute to overnutrition and undesirable increased body weight, especially in male Fischer 344/N rats. The NTP and NCTR research programs include research plans to address critical oil gavage, diet composition feeding regimen, exercise and hormonal status questions. Results of these studies will point the way to improving long-term carcinogenesis and toxicity testing. PMID- 3097654 TI - Fat-protein interaction, defined 2-generation studies. AB - Mammary tumor burden, in rats fed either normal or high fat diets related positively to the level of protein in the diet. This relationship existed with either a direct (NMU) or indirect carcinogen (DMBA). Significant differences in body growth, sexual maturation, morphologic structures in the mammary duct, and hormone activities during the estrous cycle probably contributed to lower tumor burden in the low protein-normal fat (LP-NF) group. Animals fed a high protein normal fat (HP-NF) diet throughout their entire life have, with the exception of early sexual maturation, no distinctive characteristics compared to the control group. Inspite of these physical and physiologic similarities, increased dietary protein enhanced the effect of administered carcinogens. Animals fed a high protein-high fat (HP-HF) diet were compared to rats fed a normal protein-high fat (NP-HF) diet. Increased dietary protein further enhanced the effect of the high fat diet resulting in an increased carcinogen-induced tumor burden. These studies indicate that the design of the animal model, i.e. age of initiation of a test diet, appears to have a significant bearing on mammary tumor development. The biologic mechanisms which respond to diet modifications and which may influence breast tumor growth have not been thoroughly elaborated and require additional study. PMID- 3097655 TI - The biochemical epidemiology of prostatic carcinoma. PMID- 3097656 TI - Cholesterol conundrums: the relationship between dietary and serum cholesterol in colon cancer. PMID- 3097657 TI - Role of acute caloric-restriction in murine tumorigenesis. PMID- 3097658 TI - Metabolic activation of carcinogens. PMID- 3097659 TI - Eicosanoids and cancer. PMID- 3097660 TI - Fatty acid-induced modifications of mouse mammary epithelium as studied in an organ and cell culture system. AB - The results obtained from the experiments described in this article may be summarized as follows: Mammary glands from adult mice of various strains can be maintained in a chemically defined medium for at least 23 days. The mammary epithelium in this in vitro system responds to selected steroid and polypeptide hormones in a manner similar to that observed in the explant cultures of immature mice. The incidence of spontaneous or carcinogen-induced lactogenic hormone independent, putative preneoplastic MAL has a strong correlation with the age of mouse and the risk of developing mammary cancer. Selected fatty acids that are known to modulate mammary tumor incidence are also able to alter MAL incidence in mammary gland organ cultures from a high cancer incidence strain of mouse. Nontransformed mammary epithelial cells in culture respond to the potent mammary carcinogen DMBA by exhibiting increased proliferation and specific mutation that renders the cells resistant to cytotoxic TG. Selected fatty acids modulate DMBA induced changes, at least in part, by modulating the process of metabolic cooperation between normal and mutant phenotypes. The present in vitro assays could be valuable to evaluate the direct effects of agents that initiate, promote and/or inhibit neoplastic transformation in mammary epithelium. PMID- 3097662 TI - Clinical trials of low fat diets and breast cancer prevention. PMID- 3097661 TI - Changing patterns in the dairy industry. PMID- 3097663 TI - Efficacy of different modalities of LHRH agonist (buserelin) administration on the inhibition of the pituitary-ovarian axis for the treatment of endometriosis. PMID- 3097664 TI - A preliminary report on the comparative use of buserelin (Hoe 766) and danazol in the treatment of endometriosis: the University of Southern California experience. PMID- 3097666 TI - The effect of LHRH agonist therapy in the treatment of endometriosis (Dutch experience). PMID- 3097665 TI - Effect of LH-RH agonist therapy in the treatment of endometriosis (German experience). PMID- 3097667 TI - Clinical study on finding optimal dose of a potent LHRH agonist (buserelin) for the treatment of endometriosis--multicenter trial in Japan. PMID- 3097668 TI - The effect of LHRH agonist therapy in the treatment of endometriosis (English experience). AB - The preliminary findings of a comparative study of buserelin and danazol in the treatment of endometriosis are presented. Eighty patients with laparoscopically proven symptomatic endometriosis have been allocated at random to open treatment with intra-nasal buserelin or oral danazol. Forty-five patients have been assessed after completion of seven months treatment. Changes in endometriotic lesions have been examined by second laparoscopy and scored according to a modification of the criteria of the American Fertility Society (AFS). Both treatments were associated with reductions in modified AFS scores reflecting partial resolution of the condition. Adverse effects were reported with the use of both drugs, but appeared to be more extensive during therapy with danazol. Further evaluation and post treatment follow up are required. PMID- 3097669 TI - Uterine leiomyoma: treatment with LHRH agonist. PMID- 3097670 TI - Uterine leiomyoma and LHRH agonist treatment. A preliminary report. PMID- 3097671 TI - LHRH agonist and contraception. PMID- 3097672 TI - Understanding the polycystic ovary syndrome. PMID- 3097673 TI - The effects of buserelin on the hormonal states in PCOD. PMID- 3097674 TI - The additional use of buserelin in HMG-HCG ovulation induction in PCO: a double blind controlled study. PMID- 3097676 TI - Hormonal management of cycle disturbances. PMID- 3097675 TI - Induction of ovulation in polycystic ovarian disease. PMID- 3097678 TI - Effects of chlordiazepoxide and sodium valproate in two tests of spatial behaviour. AB - The effects of chlordiazepoxide (CDP) and sodium valproate (VPA) were studied in rats trained to asymptotic performance on two tests of spatial behaviour, the 8 arm radial maze and the 8-choice arena. The task in the 8-arm maze was to locate a single food pellet at the end of each arm. Both CDP and VPA caused an increase in errors, an increase in performance time, and the utilization of a non-spatial response strategy. The task in the 8-choice arena was to locate a single water bottle from an octagonal array of eight otherwise empty bottles. For one group the goal bottle remained in the same place from trial to trial; for a second group the position of the goal bottle was cued by a black card over the nozzle; for the third group the goal bottle was uncued and moved randomly from trial to trial. VPA had no effect on performance, but CDP impaired performance in all three groups. These patterns of effects suggest that VPA may specifically disrupt working memory, but that the impairment of spatial performance by CDP probably results from a non-specific perceptual or attentional deficit. PMID- 3097677 TI - Hypothalamic control of gonadotropin secretion in the human menstrual cycle. PMID- 3097679 TI - Effects of phenobarbital in combination with phenytoin or valproic acid on the delayed-matching-to-sample performance of pigeons. AB - The present study examined the effects of phenobarbital (5, 10, 20, and 40 mg/kg), phenytoin (2.5, 5, 7.5, and 15 mg/kg), and valproic acid (40, 60, 80, and 120 mg/kg), and those of phenobarbital (10 and 20 mg/kg) in combination with phenytoin (2.5, 5, and 7.5 mg/kg) or valproic acid (40, 60, and 80 mg/kg), on the delayed-matching-to-sample performance of pigeons. In general, high doses of each individual drug reduced accuracy. Drug combinations also reduced accuracy relative to control values. Reductions in accuracy produced by drug combinations were very similar in magnitude to those predicted by a response-addition model of drug interaction. PMID- 3097680 TI - Differential effects of alpha-methyl-p-tyrosine and 6-hydroxydopamine on pentylenetetrazol seizures in mice. AB - An intraperitoneal injection of the tyrosine hydroxylase inhibitor, alpha-methyl p-tyrosine, did not alter the incidence of seizures induced by pentylenetetrazol, but increased the severity and duration of the tonic and clonic phases which resulted in death of some animals. By contrast, pentylenetetrazol seizures' characteristics were significantly changed in response to the intraperitoneal administration of the norepinephrine antagonist, 6-hydroxydopamine, by abolishing the tonic and clonic phases of the seizure. Moreover, alpha-methyl-p-tyrosine slightly attenuated the protective effect of 6-hydroxydopamine against pentylenetetrazol-induced seizures. Neurochemically, alpha-methyl-p-tyrosine significantly lowered the brain contents of both norepinephrine and dopamine while 6-hydroxydopamine caused no changes in the brain contents of these amines. PMID- 3097681 TI - [Monitoring of medication in optimalization of preoral theophylline in long-term care]. AB - A narrow therapeutic index, considerable interpatients variability of clearance and biotransformation, rapid alterations of pharmacokinetics point out theophylline to a problem-drug. An effective long-term treatment with this drug is only possible with retard-preparations. For a certain therapy a drug monitoring-controlling the theophylline-concentration in the serum--is necessary, in what extend and under which conditions is discussed in detail. PMID- 3097682 TI - Action spectra in ultraviolet wavelengths (150-250 nm) for inactivation and mutagenesis of Bacillus subtilis spores obtained with synchrotron radiation. PMID- 3097683 TI - Behavioral effects after ibotenic acid, 6-OHDA and electrolytic lesions in the central amygdala nucleus of the rat. AB - Selective lesions of central amygdaloid neurons with ibotenic acid and electrolytic destruction of the nucleus both led to marked increases in open field activity and activity during passive avoidance conditioning. However, electrolytic lesions of both neurons and fibers resulted in the most pronounced passive avoidance impairments and it is suggested that this lesion effect should be attributed to a combined destruction of intrinsic neurons and neurons located outside the central amygdala nucleus. The 6-OHDA lesions resulted in no significant changes in the behavioral parameters under investigation or in plasma corticosterone levels. The lack of reduced corticosterone levels in any of the lesioned groups do not indicate that general fear arousal is critically dependent on intact central amygdala neurons in the rat. The behavioral data are, however, still compatible with a hypothesis of a temporary reduction in fear arousal during the initial phase of the passive avoidance conditioning. PMID- 3097684 TI - Choices by rats between water and solutions of GABA or other amino acids. AB - Responses differed widely when rats were offered choices between water and solutions of GABA, its isomers alpha-aminobutyric acid (AABA) and alpha aminoisobutyric acid (AIB), or of another 4-carbon amino acid, threonine. They preferred solutions of threonine and AABA starting at concentrations of about 30 mM; preference for threonine declined when its concentration was 330 mM or above. Rats never preferred GABA or AIB, but instead avoided these amino acids when concentrations were approximately 100 mM or above. Control rats showed strong preferences for drinking from a given location. Limited studies with humans showed variations in the concentrations at which they could detect GABA; the mean was about 0.06 mM, a concentration far below that at which rats began to avoid this amino acid. The ability of dietary GABA to depress food intake of rats (as shown in earlier studies) does not seem related to a uniquely high sensitivity to its gustatory qualities. PMID- 3097685 TI - Anorexia after adrenalectomy in gold thioglucose-treated obese mice: role of adipose tissue mass. AB - We have previously shown that following adrenalectomy, gold thioglucose (GTG) treated hyperphagic obese mice exhibit anorexia, weight loss and a pronounced hypoglycemia which leads ultimately to their death. In the present study, we sought to determine whether the increased adipose tissue mass which is characteristic of GTG-treated obese mice exerted a role in the onset and development of anorexia after adrenalectomy. Accordingly, the effects of adrenalectomy on food intake, weight gain, plasma glucose and corticosterone levels were investigated in normal untreated controls, GTG-treated hyperphagic obese mice and GTG-treated non obese mice. The GTG-treated non obese mice were prepared by restricting their daily intake of chow (pair-feeding) to that consumed by normal untreated mice. After adrenalectomy, all mice were allowed free access to food. As expected, all GTG-treated hyperphagic obese mice exhibited anorexia and weight loss following adrenalectomy. In contrast, about half (52%) of the GTG-treated non obese mice exhibited anorexia and weight loss after adrenalectomy. The response of the GTG-treated non obese adrenalectomized mice was not due to differences in adrenal insufficiency since all adrenalectomized mice had blood levels of corticosterone of less than 0.5 microgram%. These findings indicate that whereas the increased adipose tissue mass of the GTG-treated obese mice appears to be associated with an increased incidence of anorexia following adrenalectomy, increased adipose tissue mass alone does not appear to be essential for the occurrence of anorexia. PMID- 3097687 TI - [Patients requiring permanent care]. PMID- 3097686 TI - Adrenalectomy induced anorexia in gold thioglucose-treated obese mice: metabolic and hormonal changes. AB - Adrenalectomy of gold thioglucose (GTG)-treated hyperphagic obese mice had been shown by us earlier to result in anorexia, weight loss, hypoglycemia and subsequent death of all mice. More recent studies suggest that adipose tissue mass may not be the critical determinant of anorexia since a large proportion of GTG-treated non obese (pair-fed to curb obesity) mice when challenged with adrenalectomy also developed anorexia. The aim of the present studies was to determine whether the changes in circulating metabolites, namely, glucose, free fatty acids and hormones, including insulin, glucagon and ACTH, which accompany adrenalectomy, might provide a clue to the causative agent for the onset of anorexia in GTG obese and non obese mice. Accordingly, plasma levels of glucose, free fatty acids, insulin, glucagon and ACTH were measured in GTG-treated obese, non obese and in normal untreated mice following adrenalectomy or a sham operation. Preoperatively, plasma insulin levels were significantly elevated in GTG obese mice whereas plasma glucose, free fatty acids and glucagon levels were not appreciably different than those of untreated controls. Upon adrenalectomy and onset of anorexia, GTG obese mice exhibited a progressive decline in blood glucose and insulin levels; plasma free fatty acids increased precipitously but only after the first day. Plasma glucagon levels declined immediately following adrenalectomy, however, by the 6th day postoperatively they were significantly elevated above the sham operated obese and untreated controls. Prior to adrenalectomy, the pair-fed GTG non obese mice exhibited blood glucose and insulin levels well below the levels of untreated controls and GTG obese mice whereas plasma free fatty acids and glucagon levels were markedly elevated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097688 TI - [Critical thoughts on the terms "Mycobacterium tuberculosis", "Mycobacterium bovis" and "Mycobacterium avium" in Bergey's Manual of Determinative Bacteriology, 8th edition, 1975, Williams-Wilkins Company, Baltimore]. PMID- 3097689 TI - [Primary resistance in the area of the District of Split]. PMID- 3097690 TI - [Late rehabilitation of psychiatric patients]. AB - The results of a catamnestic study concerning patients of a psychiatric rehabilitation unit are reported. The patients were either longterm inpatients (mean duration of stay 8.5 years) or those, who had been transferred from the acute unit for lack of therapeutic progress and thus were probable to become longterm patients. Half the patients of the first and two third of the patients of the second group could be dismissed, living alone, with their families or in home accommodations. In a very few cases occupational rehabilitation could be achieved. Predictors of good outcome were higher age of the patient at first admission to a psychiatric hospital, longer duration of occupational practise, preserved contact to the family and pecuniary security warranted by a disablement pension. Further improvements of in- and outpatient psychiatric care are discussed. PMID- 3097691 TI - Prolongation of the antidepressant response to partial sleep deprivation by lithium. AB - Depressed patients given a loading dose of lithium on the first of 2 successive days of partial sleep deprivation (PSD), and kept at maintenance levels thereafter, showed significantly greater prolongation of the antidepressant effects of PSD than patients treated with PSD and placebo, even though the acute elevation in mood derived from PSD was as great on placebo as on lithium. Depression was assessed 3 days after PSD with an augmented version of the Hamilton Rating Scale for Depression. Patients on lithium alone, without PSD, did not have the acute elevation in mood seen in the two PSD groups and had significantly less improvement in depression than those who received PSD with lithium. PMID- 3097692 TI - The TRH test during dopamine receptor blockade in depressed patients. AB - In an evaluation of the possible role of dopamine on TRH test results, 21 depressed patients were given TRH before and after one week of treatment with a low dose of haloperidol. Haloperidol significantly increased serum prolactin (both basal and after TRH) and cortisol levels, decreased body temperature, and had no effect on serum TSH, growth hormone, or thyroid hormone levels. Five of six patients with initial TSH blunting were retested with TRH; in four patients the TSH response remained blunted. These data render it unlikely that dopamine exerts a major inhibitory input on TSH secretion in depression. PMID- 3097693 TI - L-tryptophan administered to chronic sleep-onset insomniacs: late-appearing reduction of sleep latency. AB - The effects of 3 g L-tryptophan on sleep, performance, arousal threshold, and brain electrical activity during sleep were assessed in 20 male, chronic sleep onset insomniacs (mean age 20.3 +/- 2.4 years). Following a sleep laboratory screening night, all subjects received placebo for 3 consecutive nights (single blind), ten subjects received L-tryptophan, and ten received placebo for 6 nights (double-blind). All subjects received placebo on 2 withdrawal nights (single blind). There was no effect of L-tryptophan on sleep latency during the first 3 nights of administration. On nights 4-6 of administration, sleep latency was significantly reduced. Unlike benzodiazepine hypnotics, L-tryptophan did not alter sleep stages, impair performance, elevate arousal threshold, or alter brain electrical activity during sleep. PMID- 3097694 TI - Brain sites involved in the mediation of the behavioral effects of intraventricularly administered (-)-nicotine. AB - Fifteen hooded rats were trained to lever press for food under a fixed ratio (FR) 32 schedule. When lever pressing stabilized all rats were implanted with two cannulae, one in the lateral ventricle (LV) and the second in one of the following brain structures: dorsal hippocampus (DH), locus ceruleus (LC), lateral hypothalamus (LH), reticular formation (RF), or the vestibular nucleus (VN). All rats when infused with 5.0 micrograms (-)-nicotine (LV) showed an increased latency to complete the first ratio. Infusions of (-)-nicotine (0.25 microgram) into specific brain sites showed that qualitatively and quantitatively similar effects on FR performance could be produced when nicotine was infused into the VN. When lidocaine (5.0 micrograms) was applied to the RF the latency to complete the first ratio following 5.0 micrograms (-)-nicotine infusion into the LV was decreased by 55%. Lidocaine infused into the VN completely blocked the effect of LV (-)-nicotine. Neither lidocaine nor (-)-nicotine had any effect on responding when applied to the other brain structures. The results suggest that a primary site of central action of (-)-nicotine is the VN and that inhibition of the RF will attenuate the behavioral effects of LV infusions of (-)-nicotine. PMID- 3097695 TI - Potentiation of morphine analgesia by d-amphetamine. AB - Rats were trained to escape from aversive electrical brain stimulation delivered to the mesencephalic reticular formation (MRF). The threshold for this escape behavior was determined by a modification of the classic psychophysical method of limits. Escape thresholds were determined after the administration of morphine alone, d-amphetamine alone, and the combination of d-amphetamine and an ineffective dose of morphine. Morphine alone caused a dose-dependent raising of the escape threshold (1.0-16.0 mg/kg IP) while d-amphetamine alone (0.06-2.0 mg/kg IP) had no effect or caused a slight lowering of threshold. For each animal, a dose of morphine that produced no change in escape threshold was then selected to be administered concomitantly with various doses of d-amphetamine. The co-administration of morphine and d-amphetamine resulted in a significant, dose-dependent increase in the escape threshold, which was not seen with d amphetamine alone and was as great or greater in magnitude than the increase seen with the highest dose of morphine tested. The results of this study clearly demonstrate that opiate analgesia is potentiated by concomitant d-amphetamine administration. The mechanisms involved in this potentiation warrant further investigation for the clinical management of pain. PMID- 3097696 TI - Emotional hyperthermia in spontaneously hypertensive rats. AB - Basal body temperature of spontaneously hypertensive rats (SHR) was found to be significantly elevated compared to normotensive Wistar Kyoto rats (WKR). The hypothermic response to low doses of the alpha 2-receptor agonist clonidine was significantly smaller in SHR compared to WKR. In contrast, the thermoregulatory response of SHR to a non-noxious stressor was heightened. We propose that the elevated basal temperature observed in SHR is not due to an impaired thermolysis but the result of a noradrenaline-mediated hyperreactivity to environmental stress, e.g. handling of the animals during the temperature measurement procedure. PMID- 3097697 TI - The effects of FG 7142 and RO 15-1788 on the release of punished responding produced by chlordiazepoxide and ethanol in the rat. AB - Previous results in our laboratory have shown that both chlordiazepoxide and ethanol will release punished responding in a rat operant conflict test using incremental shock. In the present study, a benzodiazepine antagonist and a benzodiazepine inverse agonist were used to explore the neurochemical basis for this behavioral action. N-methyl-beta-carboline-3-carboxamide (FG 7142) at high doses (20 and 40 mg/kg) produced suppression of both punished and unpunished responding, and reversed the release of punished responding produced by both chlordiazepoxide and ethanol, but only at doses that produced an effect on its own. FG 7142 thus acted to oppose the actions of both ethanol and benzodiazepines but in an additive, not interactive, manner. In contrast, RO 15-1788 produced no changes when injected by itself in doses as high as 12 mg/kg and reversed chlordiazepoxide-induced but not ethanol-induced release of punished responding. RO 15-1788 also reversed the decrease in punished responding produced by FG 7142. Results suggest that ethanol does not interact directly with the benzodiazepine binding sites on the GABA/benzodiazepine ionophore complex to produce its anxiolytic action. PMID- 3097698 TI - Temperature dependence of ethanol depression in rats. AB - The relationship between ambient temperature, body temperature, and brain sensitivity to ethanol was investigated in rats. Drug naive male Long Evans rats were injected IP with a hypnotic dose of ethanol (2.75 g/kg, 20% w/v). Immediately after injection, separate groups were exposed to one of five ambient temperatures from 12 to 34 degrees C. Ambient temperature significantly affected wake-up rectal temperature, sleep-time, and wake-up brain ethanol concentration. Sleep-times in individual rats increased 387% (from 24.0 min at 12 degrees C to 116.8 min at 34 degrees C) and wake-up brain ethanol concentrations decreased 79% (from 3.6 mg/g at 12 degrees C to 2.3 mg/g at 34 degrees C) as body temperatures increased from 35 to 41 degrees C. In addition, wake-up rectal temperatures were significantly, positively correlated with sleep-times (r = 0.32, P less than 0.05) and significantly, negatively correlated with wake-up brain ethanol concentrations (r = -0.49, P less than 0.01), further suggesting that brain sensitivity to ethanol increases as body temperature increases. These results are consistent with previous findings in mice, fit membrane perturbation theories of anesthesia, and indicate that temperature dependence of ethanol sensitivity is a general phenomenon extending across species. In conjunction with previous findings, the results also suggest that body temperature during intoxication may participate in mediating species differences in ethanol sensitivity. PMID- 3097699 TI - Discriminative stimulus properties of the serotonin agonist MK 212. AB - In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8 OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1 (m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT1/5-HT2 antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT2 antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT1/5-HT2 but not by selective 5-HT2, antagonists suggests the possibility that 5-HT1 receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212. PMID- 3097700 TI - Influence of p-chloroamphetamine and methysergide on the escape deficits provoked by inescapable shock. AB - The effects of serotonergic manipulations on the escape interference engendered by exposure to inescapable shock were assessed. Consistent with the view that the behavioral interference was related to reductions of serotonin (5-HT), treatment with the 5-HT receptor blocker methysergide mimicked the effects of inescapable shock in that it increased escape latencies. Conversely, acute treatment with a moderate dose of the 5-HT releasing agent p-chloroamphetamine (PCA) effectively antagonized the escape interference ordinarily provoked by inescapable shock. The effects of PCA were behaviorally distinguishable from the previously observed effects of catecholamine stimulants. Whereas catecholamine stimulants applied prior to either inescapable shock or escape testing eliminated the interference, PCA antagonized the behavioral disruption only if it was administered before testing. It is suggested that catecholamine alterations may be fundamental in the provocation of the interference, whereas 5-HT variations may contribute to the expression of the behavioral disturbance. PMID- 3097701 TI - Methylphenidate and memory: dissociated effects in hyperactive children. AB - Fourteen children with Attention Deficit Disorder with Hyperactivity (ADD + H) were administered the psychostimulant methylphenidate in a double-blind, placebo controlled, crossover study. Subjects were evaluated on a well-validated measure of verbal memory and learning with an experimental design comprised of four conditions: placebo and active drug at three doses. Positive memory effects were found in the drug conditions. Significant dose-response relationships were found, indicating enhanced learning from placebo to low to medium to high dose. However, there was a differential drug effect on the memory task; methylphenidate selectively enhanced storage and retrieval mechanisms without affecting immediate acquisition. PMID- 3097702 TI - Agonist and antagonist effects of prototype opiate drugs in fentanyl dose-dose discrimination. AB - The experiments characterized the effects of fentanyl, morphine, naloxone, cyclazocine, nalorphine, ketocyclazocine and N-allylnormetazocine in rats that were trained to discriminate 0.04 mg/kg from 0.02 mg/kg fentanyl (dose-dose discrimination). The data are compared to results obtained previously in rats discriminating 0.04 mg/kg fentanyl from saline (drug-saline discrimination). In the dose-dose discrimination fentanyl and morphine produced responding appropriate to 0.04 mg/kg fentanyl at doses which were 3.0- and 1.6-fold higher, respectively, than in drug-saline discrimination. Naloxone antagonized the stimulus effects of 0.04 mg/kg fentanyl at 9.8-fold lower doses than in drug saline discrimination. The dose-effect curves of fentanyl and naloxone in rats discriminating 0.04 mg/kg from 0.02 mg/kg fentanyl, were steeper than in rats discriminating 0.04 mg/kg fentanyl from saline. While cyclazocine, nalorphine and N-allylnormetazocine acted as mixed and partial agonists/antagonists in drug saline discrimination, those compounds acted as pure and complete antagonists of 0.04 mg/kg fentanyl in dose-dose discrimination. The rank order of compounds in antagonizing the stimulus effects of 0.04 mg/kg fentanyl in dose-dose discrimination was naloxone greater than N-allylnormetazocine greater than cyclazocine greater than nalorphine. It is suggested that a greater magnitude of opiate activity is required for producing generalization with the same 0.04 mg/kg dose of fentanyl in dose-dose as compared with drug-saline discrimination. Dose dose discrimination may afford a more accurate method of the discriminative stimulus properties of drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097703 TI - Specific disruption of spatial behaviour in rats by central muscarinic receptor blockade. AB - Three groups of rats were required to locate a single water bottle from an octagonal array of eight otherwise empty bottles. For one group (place navigation) the goal bottle remained in the same place from trial to trial; for a second group (cue navigation) the position of the goal bottle was cued by a black card over the nozzle; for the third group the goal bottle was uncued and moved randomly from trial to trial. Place and cue groups improved more than controls on all measures of performance. Scopolamine (0.2 mg/kg) substantially impaired performance in the place group, but had no effect on either of the other groups; the peripherally acting anticholinergic drug meth-scopolamine (0.2 mg/kg) had no effect in any group. In a second experiment, using food rewards, scopolamine caused a dose-dependent impairment of place navigation at doses from 0.025 to 0.4 mg/kg; 0.4 mg/kg also impaired cue navigation, but at this dose behaviour was visibly abnormal. In both experiments, scopolamine primarily affected speed of performance rather than accuracy. Olfactory cues were shown not to contribute to performance in either group. The results implicate central cholinergic transmission in the processing of visuo-spatial information. PMID- 3097704 TI - Lithium effects on adjunctive alcohol consumption in rats. AB - Rats receiving chronic administration of lithium chloride (20 mEq/l) in their drinking water were tested for acquisition of adjunctive alcohol (10% v/v) consumption. Contrary to expectations, subjects receiving lithium acquired the adjunctive drinking more rapidly, and under less optimal conditions, than did control subjects. The high death rate in subjects receiving lithium while undergoing a concurrent alcohol withdrawal suggests that particular caution must be observed when lithium is used in the treatment of alcoholics. PMID- 3097705 TI - The effects of (+)-amphetamine and apomorphine on responding for a conditioned reinforcer. AB - Two psychomotor stimulants, (+)-amphetamine and apomorphine, were examined for effects on associative learning and responding for a conditioned reinforcer. The experimental phases included: preexposure to an operant test chamber with two levers, each of which produced a neutral stimulus when pressed; pairings of one stimulus with food; and a subsequent test of lever pressing for the two stimuli. Groups of food deprived rats (n = 8-12) were given IP injections of one stimulant prior to each pairing or testing session. Given during pairings, (+)-amphetamine produced a dose-related attenuation of responding for the conditioned stimulus in the test; doses of 0.5, 1.0 and 2.0, but not 0.25 or 4.0 mg/kg, given during the test enhanced responding, as did 0.5 mg/kg given in both phases. Apomorphine did not significantly alter responding during testing when administered in either the pairing (0 0.75 mg/kg) or test (0.5 1.0 mg/kg) phase. The results suggest that the modulation of conditioned reinforcement by psychomotor stimulants may occur through a presynaptic influence. Furthermore, the results with (+)-amphetamine suggest that this drug differentially affects the learning of an association between a conditioned and unconditioned stimulus versus the acquisition of responding for that conditioned stimulus. PMID- 3097706 TI - The effects of haloperidol on amphetamine- and methylphenidate-induced conditioned place preferences and locomotor activity. AB - Place preferences induced by the indirect dopamine (DA) receptor agonists amphetamine (AMP) and methylphenidate (MPD) were investigated using an unbiased compartment procedure. In this procedure, prior to drug conditioning, rats did not exhibit preferences for either of the two compartments in a shuttle box. Both stimulants produced place preferences. Repeated testing of the MPD conditioned animals revealed an extinction-like decrease in preferences, suggesting that place preferences produced by MPD result from conditioning of MPD's reinforcing properties to environmental cues. During conditioning, the DA receptor antagonist haloperidol was administered prior to drug (S+) treatments, or prior to both drug and vehicle (S-) treatments. Haloperidol pretreatment blocked place preferences induced by AMP but not by MPD. In contrast, haloperidol blocked locomotor activity stimulated by either AMP or MPD. These results suggest that the reinforcing properties of MPD and AMP may be mediated by different mechanisms, while the locomotor stimulant effects of the two drugs have common neural substrates. PMID- 3097707 TI - Apomorphine response plasticity in lesioned rats: supersensitivity dependency and lack of drug- or non-drug-associated environmental cuing. AB - Low doses of apomorphine can induce biphasic, contralateral circling behaviour in rats having unilateral, 6-hydroxydopamine lesions of the substantia nigra. The present studies examined the extent to which this is linked to the supersensitive state, the possible contribution of apomorphine's actions in the intact striatum, and the extent to which response differentiation might be linked to drug- or non drug-associated environmental cuing. In the first instance, weekly administration of 0.4 mg/kg SC apomorphine to "normosensitive" rats having electrolytic ablation of one caudate failed to result in biphasic circling, whereas clear biphasic responses developed in supersensitive, 6-hydroxydopamine lesioned animals receiving 0.05 mg/kg SC apomorphine at weekly intervals. In the second instance, 6-hydroxydopamine-lesioned animals exhibiting biphasic responses after three exposures to apomorphine continued to do so after additional electrolytic ablation of the contralateral caudate, indicating a primary role for apomorphine's interaction within the denervated striatum. In studying the possible role of drug- or non-drug-associated environmental cuing effects it was found that repeated exposure of 6-hydroxydopamine-lesioned rats to 0.05 mg/kg SC apomorphine at 2-h intervals failed to elicit biphasic responses, although these were evident when the same animals were tested 1 and 2 weeks later. However, studies combining weekly exposure to the test cages with saline or apomorphine administration failed to reveal a role of drug- or nondrug-associated environmental cuing in response differentiation. The latter findings are supported by those from supplementary studies employing opaque contact lenses, in which lesioned animals continued to respond biphasically to apomorphine when deprived of visual input.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097709 TI - The opiate antagonist naloxone does not arouse man from natural delta sleep. AB - To see if the opiate receptor/endorphin system plays a part in the regulation of natural sleep in humans the effects of the opiate antagonist naloxone on delta sleep were examined. The sleep behaviour of each of six healthy male volunteers aged 20-32 years was monitored by continuous recordings of EEG, EOG, EMG, heart rate and respiratory rate for 3 nights. The sleep stages were evaluated according to Rechtschaffen and Kales. Naloxone (0.03 mg/kg body wt.) or saline as placebo was administered intravenously in a double-blind randomized order during the spontaneously occurring delta sleep, the effects being observed on sleep behaviour and recorded variables. Naloxone never elicited arousal, either in the EEG or in the subjects' behaviour. The only effect noted was an increase in the mean latency of the first REM sleep stage. Naloxone does not arouse humans from natural delta sleep. It seems unlikely therefore, that endorphins play a role in the regulation of delta sleep in humans unless there are opiate receptor subtypes involved for which naloxone has a low affinity in man. PMID- 3097708 TI - Effects of fixed-ratio length on the development of tolerance to decreased responding by l-nantradol. AB - Key pecking of pigeons was maintained under either a 100-response or a 300 response fixed-ratio schedule of food presentation, and animals received 0.03 mg/kg/day l-nantradol prior to experimental sessions. Tolerance developed for initial rate decreases under fixed ratio 100 in 10-12 sessions, but tolerance did not develop under fixed ratio 300 for up to 30 sessions. When the fixed ratio was changed from 300 back to 100, tolerance developed in three to four sessions, and when the fixed ratio was changed from 100 back to 300, tolerance diminished in two to three sessions. The importance of fixed-ratio parameter for the observation of tolerance extends the generality of the influence of reinforcement processes on tolerance. PMID- 3097710 TI - Fluphenazine activity and antipsychotic response. AB - Plasma fluphenazine levels and plasma total neuroleptic activity (as quantitated by the neuroleptic receptor binding assay) were related to therapeutic response in 15 DSM-III schizophrenic patients who received a predetermined, fixed dose of fluphenazine for 14 days. Mean neuroleptic activity of the plasma was 84% greater than can be accounted for by the parent fluphenazine alone, and varied widely between patients. A sigmoidal relationship between total neuroleptic activity of plasma and response was found, with a continued plateau of response at higher total neuroleptic levels. Furthermore, the RBA data suggested (P less than 0.002) that two populations of drug-responsive schizophrenics exist which may be discriminated by the total D2 binding activity of plasma required for response. PMID- 3097711 TI - Reversal of scopolamine-induced amnesia by phosphatidylserine in rats. AB - Scopolamine (2 mg/kg IP) and propranolol (55 mg/kg IP), given before a single learning trial, reduce retention of a passive avoidance response in rats. Phosphatidylserine, 30-60 mg/kg IP, antagonizes the amnesic effect of scopolamine but not that of propranolol. The retention of the passive avoidance response is not affected by phosphatidylserine given alone. The results indicate that this phospholipid selectively counteracts the action of scopolamine on passive avoidance acquisition, probably via a cholinergic mechanism. PMID- 3097712 TI - Prediction of cortisol response to dexamethasone from age and basal cortisol in normal volunteers: a negative study. AB - The dexamethasone suppression test (1 mg at 23 h and 4 P.M. blood collection) was performed in 22 normal subjects. In contrast to a previous study using 0.5 mg dexamethasone and a 8-9 A.M. post-dexamethasone blood sample, age and basal cortisol level did not significantly predict postdexamethasone cortisol levels. PMID- 3097713 TI - RO 15-1788 does not influence postpartum aggression in lactating female rats. AB - Recently, Hansen et al. (1985) suggested behavioural similarities between lactating rats and non-maternal rats treated with benzodiazepines (BDZ), indicating that lactation may be associated with an increased activity state at the GABA/BDZ receptor complex similar to BDZ treatment. A logical prediction of this hypothesis is that BDZ antagonists should decrease typical maternal behaviours involved, such as aggression. We tested this hypothesis by measuring the behavioural effects of the BDZ antagonist RO 15-1788 (1.25-10 mg/kg IP) on aggressive behaviour of lactating female rats confronted with male intruders. We could not support the hypothesis; no consistent behavioural effects of RO 15-1788 on aggression were found. The implications of this finding for the proposed hypothesis are discussed. PMID- 3097714 TI - The tail suspension test: ethical considerations. PMID- 3097715 TI - Pharmacokinetics of the antidepressant drug viloxazine in normal subjects and in epileptic patients receiving chronic anticonvulsant treatment. AB - In order to evaluate the influence of chronic antiepileptic drug treatment on the kinetics of the antidepressant viloxazine (VLX), six drug-free control subjects and six epileptic patients treated with one or two anticonvulsants (phenobarbital, carbamazepine or phenytoin) were given a single oral dose of VLX (200 mg). On a separate occasion, the patients were also given 200 mg VLX by IV infusion. Plasma VLX levels were determined by GLC. Following oral dosing, VLX was rapidly absorbed from the gastrointestinal tract (peak levels at 0.5-4 h); plasma level profiles showed a considerable interindividual variability but did not differ significantly between patients and controls. Terminal half-lives were 4.3 +/- 1.5 h in the patients and 4.3 +/- 1.8 h in the controls. Clearance and volume of distribution calculated after IV dosing in the patients were 124 +/- 11 ml h-1 kg-1 and 0.73 +/- 0.28 l/kg, respectively. The absolute oral availability was 85 +/- 14%. At variance with findings reported for other antidepressants, VLX kinetics do not appear to be significantly altered by concurrent treatment with enzyme-inducing antiepileptic drugs. PMID- 3097716 TI - Behavioral and physiological effects associated with changes in muscarinic receptors following administration of an irreversible cholinergic agonist (BM 123). AB - Previous work in our laboratory has shown that the aziridinium ion of BM 123 (N [4(2-chloroethylmethylamino)-2-butynyl]-2 pyrrolidone) is a potent and selective muscarinic agonist and binds irreversibly to muscarinic receptors (mAChR). The present series of experiments was designed to study the effects of BM 123 on behavioral and physiological variables known to be sensitive to manipulations of the cholinergic neurotransmitter system. BM 123 was injected into the tail vein of Sprague-Dawley rats, reducing mAChR to approximately 10% of normal as judged by [3H](-)QNB binding. Oxotremorine was injected IV for purposes of comparison. Behavioral and physiological variables were measured daily for 26 days. Physiological variables (e.g., tremor, chromodacryorrhea, salivation, and temperature) showed effects in less than 5 min after injection and returned to their pretreatment baselines within minutes. Nociceptive thresholds, dependent on sensory-perceptual processes, showed peak changes of approximately +230% and returned to normal within hours. Motoric responses, i.e., drinking and general activity, recovered in 3-4 days. Learned responses and those requiring temporal discrimination took 8-11 days to recover and were the only responses paralleling the return of the mAChRs to their normal levels. Changes elicited by oxotremorine recovered more rapidly than those elicited by BM 123. The results suggest that the different variables measured are dependent on different densities of functional receptors. Implications for a theoretical model are discussed. PMID- 3097717 TI - HPLC with electrochemical detection to measure chlorpromazine, thioridazine and metabolites in human brain. AB - Thirteen phenothiazine compounds were separated chromatographically using high performance liquid chromatography with coulometric electrochemical detection. These could be extracted from brain tissue using direct homogenization in tetrahydrofuran followed by one centrifugation, evaporation of supernatant and reconstitution in water. Fluphenazine was used as the internal standard. The absolute lower limit of detection was approximately 50 pg/mg wet tissue, and recovery rates for most standards added to brain homogenates were greater than 85%. Chromatograms from patients receiving chlorpromazine (600 mg) and thioridazine (600 mg) are shown and endogenous brain levels quantified. The results are discussed with respect to their relevance in schizophrenic research. PMID- 3097718 TI - Inhibition of the shake response in rats by adenosine and 2-chloroadenosine. AB - Shaking movements, similar to those made by a dog when wet, were elicited in rats by immersion in ice-water, injections of icilin, a chemical that produces sensations of cold, and naloxone-precipitated morphine withdrawal. Adenosine and 2-chloroadenosine produced dose-dependent inhibition of shaking to ice-water and icilin. The 2-chloroadenosine effect was mediated centrally because the ICV dose required to produce inhibition was not effective when given IP. Caffeine antagonized the inhibitory effects of adenosine and 2-chloroadenosine. 2 Chloroadenosine suppressed morphine-abstinence shaking as well as the body weight loss that normally accompanies withdrawal. PMID- 3097719 TI - Conditional hyperthermia in response to atropine associated with a hypothermic drug. AB - In a set of experiments designed to examine learned associations between drug states, atropine sulfate (10 mg/kg) elicited a conditional hyperthermia in rats following ten treatment sessions in which the drug was paired with either chlorpromazine hydrochloride (10 mg/kg) or ethanol (2.3 g/kg), both hypothermia inducing agents. Atropine methyl nitrate, a quaternary analogue with similar peripheral effects but little central action, was ineffective as a cue in this situation. These experiments demonstrated that a sequential pairing of drug states can yield a change in an organism's response to the cue drug (the first drug in the sequence). PMID- 3097720 TI - Interaction of carbamazepine and other drugs with adenosine (A1 and A2) receptors. AB - The tricyclic anticonvulsant carbamazepine (CBZ) is effective in pain and affective disorder, but the mechanism of action for this drug has not been defined. Recently it was reported that CBZ had interaction with adenosine receptor, which is related to the inhibition of release of neurotransmitter. In the present study, we investigated the in vitro effects of CBZ and other drugs upon adenosine receptor binding using 3H-L-phenylisopropyladenosine (A1) and 3H-N ethylcarboxamidoadenosine (A2). The following results were obtained: CBZ and its derivative oxcarbazepine inhibit 3H-PIA binding at therapeutic plasma level (20 30 microM) more than they inhibit 3H-NECA binding; Theophylline and caffeine, methylxanthines, which are adenosine antagonists, inhibit both bindings; Other anticonvulsants such as phenobarbital, phenytoin and valproate and still other psychotropic drugs such as diazepam, imipramine and chlorpromazine have little or no effect on both bindings. These findings suggest that anticonvulsive and sedative effects of CBZ and its derivatives appear due to action on adenosine receptors (A1 and partially A2) at the therapeutic level and methylxanthines have stimulant and convulsant effects due to occupation on both A1 and A2 adenosine receptors. PMID- 3097721 TI - Effects of adrenaline on the acquisition and maintenance of ethanol preference in a taste conditioning paradigm. AB - The effects of subcutaneous adrenaline administration on preference for ethanol (2.5% solution) have been investigated, using a two-bottle choice situation. Administration of the amine (50 micrograms/kg) immediately after the conditioning session significantly attenuated ethanol preference. Adrenaline treatment (10, 50 or 100 micrograms/kg) prior to the first retention test induced a significant reduction in ethanol preference. When the amine was injected prior to conditioning only the dose of 100 micrograms/kg reduced later ethanol preference. Our results indicate that systemically administered adrenaline impairs the acquisition of preference to a weak ethanol solution. It is suggested that this effect of the amine may be linked to interference with consolidation of memory and retrieval processes. PMID- 3097722 TI - Drug discrimination procedures: differential characteristics of the drug A vs drug B and the drug A vs drug B vs no drug cases. AB - Two groups of pigeons with a history of two choice operant drug discrimination tasks (3.0 mg/kg morphine versus 5.6 mg/kg cocaine, and 3.0 mg/kg morphine versus 3.0 mg/kg cocaine, respectively; Swedberg and Jarbe 1985) were subjected to three choice tasks in which responses on a third manipulandum were reinforced in the no drug condition. Training drugs generalization gradients in both groups were similar to those normally obtained in two choice drug versus no drug tasks. The salience differences between the training stimuli within the groups observed in the previous two choice task did not differentially affect the three choice discrimination gradients. Tests with novel drugs after the introduction of the no drug condition yielded increased responding to the no drug condition with the exception of the dopamine agonist apomorphine. Results are discussed in terms of a discrimination learning model specifying principles of relative discriminative stimulus control in various discrimination cases. PMID- 3097723 TI - New approaches to postmarketing surveillance. AB - As part of a large-scale ongoing project exploring new pharmacy-based methods of postmarketing surveillance, we are comparing a patient-initiated monitoring system to a staff-initiated approach. Here we report data only from staff initiated, computer-directed telephone interviews with 231 outpatients approximately 2 weeks after they had been prescribed a target drug chosen from two markedly different pharmacological classes for which adverse drug reactions (ADRs) are well-documented. Our results indicate that spontaneous patient reports of "new or unusual symptoms" obtained from a standardized staff-initiated telephone interview can be quite reliable, leading to accurate detection of known tricyclic antidepressant and antibiotic ADRs. PMID- 3097724 TI - Dopamine agonist-induced stereotypic grooming and self-mutilation following striatal dopamine depletion. AB - Rats with bilateral 6-OHDA-induced striatal lesions exhibit altered apomorphine induced behavior compared to the typical response seen in intact rats. This response is characterized by stereotypic grooming behavior which is transformed to compulsive and intense biting at higher doses. Other agonists, pergolide, bromocriptine, N-n-propylnorapomorphine and L-dopa/carbidopa, caused the same response. Direct intrastriatal infusion of apomorphine after 6-OHDA-induced lesions of the striata also produced this response, while similar SKF 38393 infusion caused more licking than biting, directed at the abdomen instead of the forepaws. The dopamine receptor antagonists haloperidol, SCH 23390 and sulpiride effectively blocked apomorphine-induced behaviors in dopamine-depleted animals. This altered behavior was not observed in rats with dopamine depletion in nucleus accumbens (NAS), nor did additional NAS lesions in rats with existing striatal lesions affect the behavior. Further, high doses of apomorphine (up to 60 mg/kg) failed to induce stereotypic grooming in unlesioned rats. We therefore propose that altered apomorphine-induced behavior is a unique consequence of striatal dopamine depletion and not just an intense form of normal stereotypic activity. PMID- 3097725 TI - Effects of physostigmine on memory test performance in normal volunteers. AB - The effects of an intravenous infusion of physostigmine (0.94 mg infused over 60 min) on performance in memory tests were studied in 12 young subjects. Drug effects were modest and are discussed in relation to results of physostigmine studies in Alzheimer patients. PMID- 3097726 TI - The cardiovascular effects of nicotine during stress. AB - The acute cardiovascular effects of smoking during stress may be greater than those of smoking or stress alone, a finding which could have implications for determining which smokers may be at particular risk for coronary heart disease (CHD). Methodological problems inherent in using tobacco smoking to deliver nicotine (believed responsible for smoking's cardiovascular effects) prevent clear examination of the cardiovascular effects of inhaled nicotine. This study compared the cardiovascular increases due to a video game stress task plus 1.0 mg nicotine with those of stress or nicotine alone using an aerosol method of presenting nicotine in measured doses. Twelve young male smokers each participated in four conditions on 4 separate days: stress + nicotine, stress + placebo (stress alone), rest + nicotine (nicotine alone), and rest + placebo. The effects of stress and nicotine were additive for heart rate but less than additive for systolic and diastolic blood pressure. These results indicate that the combined effects of stress and nicotine may be relevant to understanding the prevalence of CHD among smokers. They also suggest that the effects of each on cardiovascular activity may be different, as the effects are independent for heart rate but overlap for blood pressure. PMID- 3097727 TI - Modification of visual orientation illusions by drugs which influence dopamine and GABA neurones: differential effects on simultaneous and successive illusions. AB - The effects of haloperidol, nomifensine and lorazepam on the visual tilt illusion were studied in normal volunteers. Haloperidol and nomifensine produced no significant changes in the illusion, although in previous work they had been found to reduce and enhance, respectively, a closely related illusion, the tilt aftereffect. By contrast, lorazepam produced a dose-related increment in the size of the tilt illusion, but had no effect on the tilt aftereffect. The results are discussed in relation to proposed mechanisms which may underlie the two kinds of illusion. The differential effects of individual drugs on the two illusions may reflect their differing actions on two processes: lateral inhibition and adaptation in visual channels. PMID- 3097728 TI - Platelets and biogenic amines. 2. Indications for a discrete low affinity uptake mechanism shared by norepinephrine and 5-hydroxytryptamine in human platelets. AB - The uptake of norepinephrine (NE) by human platelets at 10(-9)-5 X 10(-4) M of labelled amine concentration was investigated. At physiological concentrations of NE the uptake was unsaturable and could not be inhibited by imipramine or ouabain. At NE concentrations between 25 and 485 microM the uptake also comprised a saturable component that could be completely blocked by imipramine and partly by ouabain. The saturable uptake of NE had an apparent Km of 273 +/- 50 microM and a Vmax of 0.19 +/- 0.05 pmole/10(6) platelets/min. The affinity of NE (IC50) for the 5-HT transporting carrier was 2.3 mM, 8.4 times higher than the apparent Km for saturable NE uptake. The affinity of 5-HT (IC50) for the NE-transporting carrier was 5.8 microM, 5.8 times higher than the apparent Km for saturable 5-HT transport. Imipramine and norzimeldin were equipotent inhibitors of saturable NE uptake, the potency being of the same degree as that for saturable 5-HT uptake. The tertiary amine amitriptyline was 6 times more effective in inhibiting saturable NE uptake than its demethylated product nortriptyline. Nortriptyline and its hydroxylated E- and Z-isomers had a stronger inhibitory effect on saturable NE uptake than on uptake of 5-HT. The results suggest that human platelets possess two separate amine-transporting carriers, both having their highest affinity for 5-HT. The one with the lowest affinity for 5-HT can also accept NE as a substrate. The human platelet does not possess a high-affinity uptake system for NE comparable to that in adrenergic tissue. PMID- 3097729 TI - 6-Hydroxydopamine lesions of the nucleus accumbens, but not of the caudate nucleus, attenuate enhanced responding with reward-related stimuli produced by intra-accumbens d-amphetamine. AB - Intra-accumbens d-amphetamine enhances responding for reward-related stimuli (conditioned reinforcers, CRs), whereas intra-caudate d-amphetamine has only weak and variable effects (Taylor and Robbins 1984). The present experiment further examined the involvement of the nucleus accumbens and the role of dopamine (DA) in this effect. Thirsty rats were trained to associate a flash of a light and movement of a dipper (CR) with water. After implantation of permanent guide cannulae aimed at the nucleus accumbens, they were assigned to one of four groups, receiving either bilateral 6-OHDA (4 mg/ml free base in 2 microliters 0.1% ascorbic acid/0.9% saline) or sham (vehicle) infusions into the nucleus accumbens or the caudate nucleus. In the test phase, two novel levers were available. Responding on one lever (CR lever) produced the light and dipper stimuli without water presentation, whereas responding on the other (NCR lever) had no effect. All four groups received four counterbalanced intra-accumbens infusions of d-amphetamine (3, 10, 20 micrograms/2 microliters) or vehicle. On the 5th test day, subjects were pretreated subcutaneously with apomorphine (0.1 mg/kg). Intra-accumbens d-amphetamine in both sham-lesioned groups produced a dose-dependent increase in responding on the CR lever, but no significant change on the NCR lever. No selective increases in responding on either lever were found in animals with 6-OHDA-induced depletion of DA (greater than 80%) in the nucleus accumbens following intra-accumbens d-amphetamine; however, in subjects with DA depletion of the posterior caudate nucleus (greater than 80%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097731 TI - Potentiation of disruptive effects of dextromethorphan by naloxone on fixed interval performance in rats. AB - A centrally acting antitussive agent dextromethorphan (DM) was tested to determine its possible interaction with naloxone in rats responding under a fixed interval schedule of positive reinforcement. A sugar sweetened milk reward was used as a positive reinforcer. Under the same experimental conditions the effects of morphine alone and in combination with naloxone were also determined. Low dose DM (10 mg/kg) produced a slight increase, while higher doses (20-40 mg/kg) produced dose-dependent decreases in response rate. Morphine (0.3, 1.0 and 3.0 mg/kg) produced dose-dependent decreases in response rate. When doses of naloxone (0.1-1.0 mg/kg) were administered after the injection of DM the rate-decreasing effects of DM were potentiated even after the rate-increasing dose of naloxone (0.1 mg/kg) was used. When a dose of naloxone (0.1 mg/kg) was administered after the injection of morphine the rate-decreasing effects of morphine were markedly antagonized, i.e., the morphine dose-response curve was shifted to the right. The observed potentiation of DM disruption by naloxone on fixed-interval performance in rats is consistent with findings showing that naloxone potentiates the disruptive behavioral effects of a number of drugs that are psychotomimetic in man. PMID- 3097730 TI - The effect of lithium on 5-HT-mediated neuroendocrine responses and platelet 5-HT receptors. AB - The effect of lithium on serotonin (5-HT)-mediated responses in the brain was assessed by measuring changes in the prolactin (PRL) and growth hormone (GH) responses to L-tryptophan (LTP) in eight normal subjects. On the 4th day of lithium treatment the PRL responses were significantly enhanced, and this enhancement was still apparent after 20 days' treatment. In contrast, GH responses to LTP were not altered. Lithium had no effect on platelet 5-HT content, platelet imipramine binding and platelet 5-HT receptor binding. The ability of lithium to enhance some aspects of brain 5-HT function may be important in its mode of action in manic-depressive illness and may be particularly relevant to its potentiation of the antidepressant effect of tricyclic antidepressants. PMID- 3097733 TI - Why do some antidepressants promote suicide? PMID- 3097732 TI - Behavioral effects of adenosine analogs in squirrel monkeys: relation to adenosine A2 receptors. AB - The behavioral effects of seven metabolically stable analogs of adenosine were studied in squirrel monkeys responding under a fixed-interval (FI) schedule of stimulus-shock termination. All drugs produced dose-related decreases in response rate, but differed in potency by up to three orders of magnitude. The 5' carboxamide and 2-chlorine substituted analogs were more potent than the N6 substituted analogs. The potencies of the adenosine analogs in decreasing schedule-controlled behavior correlate well with their reported affinities for adenosine A2, but not A1, recognition sites as determined by displacement of bound ligands or modulation of adenylate cyclase activity. The results suggest that the behavioral effects of adenosine analogs in squirrel monkeys are linked to their actions at adenosine A2 receptors. PMID- 3097734 TI - Studies on schistosomiasis in the Niger Delta: prevalence of Schistosoma haematobium among inhabitants of Ahoada District. PMID- 3097735 TI - The 1985 health promotion and disease prevention survey. AB - The National Center for Health Statistics, in collaboration with the Office of the Assistant Secretary for Health and other Federal Agencies, developed a questionnaire on health promotion and disease prevention for the 1985 National Health Interview Survey. The answers to the questionnaire, obtained from a probability sample of the civilian noninstitutionalized population of the United States, provide trend and baseline data to track progress toward the 1990 national health objectives. The questions concerned topics related to the objectives in the following areas: general health (including nutrition), injury control, high blood pressure, stress, exercise, smoking, alcohol use, oral health, occupational safety and health, and maternal health. Data from that survey have been used by Public Health Service authors to prepare a series of 11 articles. Five are presented in this issue of Public Health Reports; the remaining six will be published in the January-February 1987 issue of Public Health Reports. This paper, which introduces the series, provides a description of the objectives of the study, the survey methods employed, and the availability of public use data tapes. PMID- 3097736 TI - Health habits of U.S. adults, 1985: the "Alameda 7" revisited. AB - Seven health habits, commonly referred to as the "Alameda 7," were shown to be associated with physical health status and mortality in a pioneer longitudinal study initiated in 1965 in Alameda County, CA. These habits are having never smoked, drinking less than five drinks at one sitting, sleeping 7-8 hours a night, exercising, maintaining desirable weight for height, avoiding snacks, and eating breakfast regularly. The Alameda study focused attention on the importance of everyday practices for the maintenance of good health and, ultimately, for longer life. This report presents selected findings on the prevalence of the seven Alameda practices (defined slightly differently in some cases) among the general U.S. population aged 18 years and older, by sex, according to age, education, income, and race. In general, men are more likely than women to smoke, drink, and exercise. Younger people are more likely than older people to skip breakfast, snack, and drink, and younger women are more likely than older women to smoke. Education, income, and racial differences were found for most health practices. Of all subgroups discussed, blacks, particularly black women, are the most likely to have lifestyles that would be considered unhealthy using the Alameda criteria. Overall, the data reported suggest that although large numbers of U.S. adults have healthy habits, many do not, particularly persons in socially and economically disadvantaged groups. PMID- 3097737 TI - Tracking 1990 objectives for injury prevention with 1985 NHIS findings. AB - The Health Promotion and Disease Prevention Survey, a component of the 1985 National Health Interview Survey (NHIS), contained a set of questions on injury control and child safety and health. The data collected from the responses were used to evaluate progress toward achieving three of the 1990 objectives for the nation related to injury prevention. Those three objectives concerned the proportions of households with a properly placed and functioning smoke detector (63.2 percent, as shown by the survey), parents who can identify appropriate measures to address the risks to their children of motor vehicle injuries, burns, and poisonings (39.1 percent), and primary health providers who advise their patients about the importance of using safety belts and child restraint devices in cars (47.0 percent). Further, information was gathered on the proportion of adults using seatbelts all or most of the time (35.5 percent) and the proportion of those who knew the range of hot water temperatures (120 degrees to 130 degrees F.) above which scald injuries can occur (21.3 percent). In general, the data demonstrated a direct relationship of injury prevention awareness to education and income. In the future it will be important to demonstrate that increasing injury awareness has a measurable, beneficial impact on injury mortality and morbidity rates. PMID- 3097738 TI - Status of the 1990 physical fitness and exercise objectives--evidence from NHIS 1985. AB - The 1985 National Health Interview Survey (NHIS) Health Promotion and Disease Prevention Questionnaire provides information regarding the status of 4 of the 11 physical fitness and exercise objectives for 1990. A specially developed scoring algorithm was used to determine the percentage of persons participating in appropriate physical activity (that is, "exercise which involves large muscle groups in dynamic movement for periods of 20 minutes or longer, 3 or more days per week, and which is performed at an intensity of 60 percent or greater of an individual's cardiorespiratory capacity" and three other categories: regular activity, but not appropriate physical activity; irregular activity; and those who were sedentary. Results revealed that the young and persons of relatively high socioeconomic status are more likely to perform appropriate physical activity in their leisure time. When rigid criteria were used, only 5.1 percent of those surveyed knew the appropriate duration, frequency, and intensity of physical activity needed to strengthen the heart and lungs. It was not possible to determine if exercise prevalence has increased in recent years; however, it will be possible to detect trends in the future when this survey is repeated in 1990. PMID- 3097739 TI - Drinking levels, knowledge, and associated characteristics, 1985 NHIS findings. AB - Several questions in the 1985 Health Promotion and Disease Prevention Questionnaire, which was part of the 1985 National Health Interview Survey, addressed respondents' consumption of alcohol. Sociodemographic characteristics, knowledge of health risks related to heavy drinking, health practices, and the prevalence of certain health conditions were examined in relation to drinking levels. Although cause-effect relationships should not be inferred from the associations, the findings suggest some provocative areas for prevention and research. Heavier drinkers were more commonly found among men than women. Level of drinking was associated positively with years of education and family income, but was inversely related to age. Compared with light drinkers, heavier drinkers were much more likely to drive after they had had too much to drink. While more than 90 percent of the population knew that heavier drinking increases the risk of 'liver cirrhosis, less than half knew about the increased risk of throat cancer and cancer of the mouth. Most respondents aged 18-44 years (80 percent or more) knew that heavy drinking increases the chance of adverse pregnancy outcomes, and more women than men (62 versus 49 percent) had heard of fetal alcohol syndrome (FAS). However, 70 percent or more of those who had heard of FAS described the syndrome as a newborn addicted to alcohol rather than a child born with certain birth defects. Heavier drinkers of both sexes were less likely than others to be nonsmokers, and moderate drinkers were more likely than others to exercise or play sports regularly. Moderate drinkers also tended to have lower lifetime prevalence rates than others for hypertension and heart trouble. PMID- 3097740 TI - Hypertension knowledge, attitudes, and behavior: 1985 NHIS findings. AB - Data from the Health Promotion/Disease Prevention Supplement to the 1985 National Health Interview Survey provide an indication of progress made toward achieving the 1990 objectives for the nation. Survey results showed remarkably high levels of knowledge concerning the increased risks associated with uncontrolled high blood pressure. Nine of 10 adults in the United States knew that high blood pressure increases the risk of heart disease, and 3 of 4 knew that high blood pressure is the most significant risk factor for stroke. The majority of both the general public and the subgroup of the population identified as hypertensives reported knowing the results of their last blood pressure measurement; and, most importantly, almost two-thirds of the identified hypertensives reported that their pressures were under control at last measurement. Data examining professional advice, given and acted upon to achieve blood pressure goals, show that almost two-thirds of the hypertensives currently report taking antihypertensive medication. Results also suggest a degree of willingness by both professionals and hypertensives to attempt nondrug approaches to controlling pressures. The large majority of hypertensives who were advised by a health professional to cut down on sodium, lose weight, and exercise reported they were following this advice. These findings will be used to further refine high blood pressure education strategies and advance the progress toward meeting the 1990 hypertension objectives. PMID- 3097741 TI - Prenatal participation in WIC related to Medicaid costs for Missouri newborns: 1982 update. AB - This study replicates a 1980 evaluation of WIC prenatal participation in Missouri by using a file of 9,086 Missouri Medicaid records matched with the corresponding birth records. This file was divided into a WIC group containing 3,261 records and a non-WIC group of 5,825 records. The 1982 results generally confirm the 1980 results, with the 1982 findings showing slightly improved pregnancy outcomes for WIC participants and slightly reduced benefit-to-cost ratios compared with the 1980 findings. In 1982, WIC participation was found to be associated with an increase in mean birth weight of 31 grams and reductions in low birth weight rates (statistically significant) and in neonatal death rates (not statistically significant). The reduction in each rate was 23 percent. WIC participation was also associated with a reduction in Medicaid costs for newborns reported within 45 days of birth amounting to $76 per participant. For every dollar spent on WIC, about 49 cents in Medicaid costs were apparently saved. However, wide 95 percent confidence intervals ($.07, $.90) make it difficult to determine precisely what impact WIC has on Federal and State budget outlays. PMID- 3097742 TI - Training faculty in Bangladesh to use a microcomputer for public health: followup report. AB - In 1984 the Western Consortium for the Health Professions, Inc., under contract to the United Nations Fund for Population Activities (UNFPA), began a project to assist Bangladesh's National Institute for Preventive and Social Medicine (NIPSOM) in establishing a microcomputing capability. The project's goal was to enable NIPSOM to become self-sufficient in the analysis by microcomputer of health, population, and family planning data; program evaluation; and policy activities. Lack of a local microcomputer infrastructure demanded that a local team of experts be developed to run the system described in a previous report. Five NIPSOM faculty members--three of whom had taken the workshop held when the system was first installed--were assigned to a computer committee, which was responsible for the computer's well-being. Six months after the microcomputer system was installed, a second 2-week workshop was given. The consortium's consultant facilitated the development of a basic microcomputer course, which was taught by four members of the computer committee to an additional eight NIPSOM faculty members. Emphasis was placed on developing local self-reliance and the need to overcome obstacles imposed by the lack of local hardware and software support systems. A strategy is proposed for the successful introduction of microcomputers in developing countries. PMID- 3097743 TI - Public health and food safety: a historical association. AB - Since the initial passage in 1906 of the first Pure Food and Drug Act and the Meat Inspection Act, public health, as measured by mortality trends, has greatly improved. These acts have been amended several times, and other laws dealing with safety of foods and drinks have been enacted. Food- and beverage-transmitted infectious diseases that were so devastating after the Civil War have been controlled. Nutritional deficiencies such as pellagra are almost nonexistent. Mass episodes of poisoning of food by chemical contaminants that have plagued some other countries have not occurred in the United States. Other factors such as refrigeration and improved transportation have helped, but it is probable that food safety regulatory activities have contributed to the saving of the 1.8 million Americans who would die each year if the public health advances since 1900 had not been made. Effective use of information was a key factor in the improvement in public health. Now, as then, effective information systems are needed. PMID- 3097744 TI - Community injury control programs of the Indian Health Service: an early assessment. AB - In response to the high rates of injury morbidity and mortality among Native Americans, the Indian Health Service initiated community injury control programs in 1982 mainly aimed at educating the populations served. Substantial declines in hospitalization rates per population for falls, motor vehicle injuries, and assaults were observed through 1984. Regression analyses of changes in hospitalization rates for particular types of injury in relation to rates of persons served in 54 service units suggests some favorable effect of certain activities and possible adverse effect of a few. Increased targeting of effort based on detailed surveillance of serious injuries is planned. PMID- 3097745 TI - Urban AHECs: a comparison with rural AHECs. AB - The first generation of projects in the Federal Area Health Education Center (AHEC) Program was funded in 1972. Those AHEC projects, located in predominantly rural areas, focused on problems that resulted from the geographic maldistribution of health professionals, especially primary care physicians. Education programs for health professionals, students, and practitioners were used to influence the geographic distribution of health professionals and to improve access to and quality of health care for underserved populations. In 1976, the Congress redrafted the law authorizing the expenditure of funds for AHECs and emphasized that improving access to health care in urban underserved areas also was to be addressed by the program. During the early years of urban AHEC development, it was not clear which lessons learned from rural AHEC experiences could be applied to urban communities and what would be the best focus for AHEC activities in the complex urban environment. Some said that urban areas were so different from rural areas--in economic, racial, and cultural terms and in the subtlety of barriers to health care--as to make the rural AHEC experience largely irrelevant. Others maintained that basic AHEC principles could be applied, regardless of setting, with changes only in tactics to address the problems of the urban inner city. Now that 18 of the total 53 AHECs nationally are urban, and a decade of experience in developing them has been accumulated, it is appropriate to compare the types of educational interventions supported by AHECs in urban and rural environments and the relative priorities of such programs. In this report we examine the experiences of the California AHEC System, which includes 17 urban and rural centers and the 9 medical schools with which they are affiliated. Although the AHEC Program concept was found to be equally applicable to both urban and rural settings, significant differences in implementation were noted. Those differences were evidenced both by relative budgets,such as the large expenditures for undergraduate medical education in urban areas and for nursing in rural areas, and by subtler differences in the types of programs developed within budget categories PMID- 3097746 TI - Use of health care by chronically ill children in rural Florida. AB - Factors that influence ambulatory care (visits to physicians and emergency rooms) and use of hospitals were investigated in a population of chronically ill, rural, low-income children. Rates of use for this population--a stratified random sample of 672 Medicaid-eligible children under age 17 years who lived in a 24-county area of northern Florida--were similar to those in a national study of chronically ill children. Further, the rates were shown to increase significantly as limitations to activity increased. Younger children and white children were also shown to have significantly higher use rates than older children and black children. Despite these associations, and those related to primary diagnoses, none of the analyses were able to explain much of the variation in the use of health care resources. The findings were similar to those of other studies; thus, the identification of the relatively small numbers of children who consume relatively large amounts of health care remains elusive. PMID- 3097747 TI - Smoking behavior among student nurses: a survey. AB - The study describes the smoking habits of student nurses and determines the correlates of smoking initiation, continuation, and cessation. The sample included 1,163 students attending 10 nursing schools in Buffalo, NY. Data were gathered by means of a self-administered questionnaire. Approximately 30 percent of the students were current smokers, 25 percent were exsmokers, and 45 percent had never smoked. More than half of the smokers (57 percent) expressed the desire to quit, and 81 percent had tried to do so in the past. Major reasons for trying to quit were to protect future health, save money, self-discipline, and pressure from significant others. Most (90 percent) of the students who had tried to quit had attempted to do so on their own and all at once. Knowledge of the health consequences of smoking was not significantly related to smoking behavior. These data suggest the need for health educators to promote personal health practices among their students that are congruent with the goals of the nursing profession of health promotion and disease prevention. PMID- 3097748 TI - The effect of hyperinsulinaemia on glucose utilization and oxidation and on oxygen consumption in the fetal lamb. AB - In order to measure the effect of hyperinsulinaemia on fetal glucose metabolism and oxygen consumption, we applied the glucose-clamp technique to experiments in fifteen late-gestation, unstressed, chronically catheterized fetal lambs. In a control period, and immediately thereafter following 2 h of hyperinsulinaemia, we measured fetal glucose utilization and oxidation rates (radioactive tracer methodology) and net fetal uptake rates of exogenous glucose and oxygen uptake rates (Fick principle). During the period of hyperinsulinaemia, fetal glucose concentration was maintained at the average control period value by a variable rate of glucose infusion into the fetus in response to serial 10 min measurements of fetal arterial blood glucose concentration. Hyperinsulinaemia in the fetus (12.12 +/- 1.92 ng X ml-1 (mean +/- S.E.M.) arterial plasma) resulted in a 13% increase in net fetal oxygen uptake rate (0.310 +/- 0.011 to 0.349 +/- 0.012 mmol. min-1 X kg-1), a 106% increase of fetal glucose uptake rate (4.54 +/- 0.43 to 9.35 +/- 0.50 mg X min-1 X kg-1) and an 83% increase of fetal glucose utilization rate (4.94 +/- 0.43 to 9.05 +/- 0.83 mg X min-1 X kg-1). Fetal glucose uptake and utilization rates were not different from each other during the control and the hyperinsulinaemia periods. The fraction of glucose that was oxidized (0.58 +/- 0.05, control; 0.54 +/- 0.05, hyperinsulinaemia) did not change significantly; thus the glucose oxidation rate, the rate of entry of glucose into non-oxidative pathways, and the amount of oxygen used for glucose oxidation all increased in proportion to glucose utilization. These results suggest that insulin promotes the entry of glucose into fetal tissues, thereby increasing fetal glucose utilization and oxidation rates and substituting glucose oxidation for that of other substrates. The insulin-enhanced glucose utilization rate also increases slightly fetal metabolic rate. PMID- 3097749 TI - Effects of scavengers of reactive oxygen and radical species on cell survival following photodynamic treatment in vitro: comparison to ionizing radiation. AB - The effects of various scavengers of reactive oxygen and/or radical species on cell survival in vitro of EMT6 and CHO cells following photodynamic therapy (PDT) or gamma irradiation were compared. None of the agents used exhibited major direct cytotoxicity. Likewise, none interfered with cellular porphyrin uptake, and none except tryptophan altered singlet oxygen production during porphyrin illumination. The radioprotector cysteamine (MEA) was equally effective in reducing cell damage in both modalities. In part, this protection seems to have been induced by oxygen consumption in the system due to MEA autoxidation under formation of H2O2. The addition of catalase, which prevents H2O2 buildup, reduced the effect of MEA to the same extent in both treatments. Whether the remaining protection was due to MEA's radical-reducing action or some remaining oxygen limitation is unclear. The protective action of MEA was not mediated by a doubling of cellular glutathione levels, since addition of buthionine sulfoximine, which prevented glutathione increase, did not diminish the observed MEA protection. The hydroxyl radical scavenger mannitol also afforded protection in both kinds of treatment, but it was approximately twice as effective in gamma irradiation as in PDT. This is consistent with the predominant role of OH radicals in ionizing radiation damage and their presumed minor involvement in PDT damage. Superoxide dismutase, a scavenger of O2, acted as a radiation protector but was not significantly effective in PDT. Catalase, which scavenges H2O2, was ineffective in both modalities. Tryptophan, an efficient singlet oxygen scavenger, reduced cell death through PDT by several orders of magnitude while being totally ineffective in gamma irradiation. These data reaffirm the predominant role of 1O2 in the photodynamic cell killing but also indicate some involvement of free radical species. PMID- 3097751 TI - Reappraisal of the role of radiation therapy in the management of Hodgkin's lymphoma with large intrathoracic masses. AB - Patients diagnosed as having Hodgkin's lymphoma with large intrathoracic masses are nowadays generally treated with a combination of chemotherapy and radiation therapy. This approach is usually indicated for more advanced stages and for cases with extranodal extension and presentation. However, the same policy is often implemented even in patients with early stage disease whenever they present with voluminous mediastinal and/or hilar masses. Especially in young persons, this approach to treatment has life-long lasting repercussions on both their general health and social fulfillment. In this article, an alternative approach is suggested. It consists of protracted, high-dose radiation therapy to the large tumor masses using the shrinking field technique and with a dose in the range of 50 to 60 Gy delivered over an approximately 3-month period. This proposition is based on the author's clinical experience and is documented in the article. PMID- 3097750 TI - Ionizing radiation promotes protozoan reproduction. AB - This experiment was performed to determine whether ionizing radiation is essential for maximum growth rate in a ciliated protozoan. When extraneous ionizing radiation was reduced to 0.15 mrad/day, the reproduction rate of Tetrahymena pyriformis was significantly less (P less than 0.01) than it was at near ambient levels, 0.5 or 1.8 mrad/day. Significantly higher growth rates (P less than 0.01) were obtained when chronic radiation was increased. The data suggest that ionizing radiation is essential for optimum reproduction rate in this organism. PMID- 3097752 TI - Use of CO2 to move structures as an aid to percutaneous procedures. AB - By injecting small amounts of CO2 through a needle, one can move bowel or bladder from the intended path of instruments during interventional procedures. The technique worked well in six of seven cases in the pelvis and retroperitoneum; it was not effective in the mediastinum or midabdomen (n = 6). PMID- 3097755 TI - Rehabilitation of the coronary patient: status 1986. PMID- 3097753 TI - Double-contrast barium enema study: simple conversion to CO2. AB - The use of CO2 instead of room air for double-contrast barium enema (DCBE) studies has been shown to decrease discomfort after the study. An inexpensive system assembled from materials currently used to perform pneumocolon examinations is described, which simplifies conversion to CO2 use for the DCBE study. No changes in currently used pneumocolon techniques are necessary with the use of CO2. PMID- 3097754 TI - Metabolites of antiarrhythmic drugs: are they clinically important? PMID- 3097756 TI - Nutrition, immune response, and outcome. AB - The immune system plays a key role in the body's ability to fight infection and reduce the risk of developing tumors, autoimmune and degenerative disease. Nutritional deficiencies and excesses influence various components of the immune system. Early studies investigating the association between nutrition and immunity focused on generalized protein-energy malnutrition, particularly in children in developing countries. The extent of immunological impairment depends not only on the severity of malnutrition but on the presence of infection and on the age of onset of nutritional deprivation, among other factors. In industrialized nations, immune function has been shown to be compromised in many malnourished hospitalized patients, small-for-gestational age infants, and the elderly. Obesity also may adversely influence immune function. Imbalances of single nutrients are relatively uncommon in humans, and investigations of protein and amino acids and specific vitamins, minerals, and trace elements generally are carried out in experimental animals. Deficiencies of protein and some amino acids, as well as vitamins A, E, B6 and folate, are associated with reduced immunocompetence. In contrast, excessive intake of fat, in particular polyunsaturated fatty acids (e.g. linoleic and arachidonic acids), iron, and vitamin E are immunosuppressive. Trace elements modulate immune responses through their critical role in enzyme activity. Both deficiency and excess of trace elements have been recognized. Although dietary requirements of most of these elements are met by a balanced diet, there are certain population groups and specific disease states which are likely to be associated with deficiency of one or more of these essential elements. The role of trace elements in maintenance of immune function and their causal role in secondary immunodeficiency is increasingly being recognized. There is growing research concerning the role of zinc, copper, selenium, and other elements in immunity and the mechanisms that underlie such roles. The problem of interaction of trace elements and immunity is a complex one because of the frequently associated other nutritional deficiencies, the presence of clinical or subclinical infections which in themselves have a significant effect on immunity, and finally the altered metabolism due to the underlying disease. There are many practical applications of our recently acquired knowledge regarding nutritional regulation of immunity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3097757 TI - The stress response to surgical trauma: from physiological basis to therapeutic implications. AB - The response to surgical injury is mediated through the hypothalamus and is characterised by the release of catecholamines, glucocorticoids, growth hormone and glucagon; the suppression of insulin secretion and changes in other endocrine systems. These hormonal responses trigger a cascade of metabolic adjustments leading to catabolism and substrate mobilization in the postoperative period. There is evidence that a severe and prolonged catabolic reaction to injury may be associated with an increased morbidity and mortality in high-risk adult patients. This article reviews the historical background of investigation in this field, together with recent advances in the understanding of the complex metabolic phenomena following surgery. These changes are discussed with particular reference to therapeutic manipulation of the stress response using anaesthetic, hormonal or nutrition regimens. It is concluded that further research in this field may provide major clinical benefits in the management of critically ill patients undergoing surgical stress. PMID- 3097758 TI - [Phylogeny and evolution of immunoglobulins]. PMID- 3097759 TI - Biphasic response of intimal prostacyclin production during the development of experimental atherosclerosis. AB - Feeding a cholesterol rich diet (0.3%) to rabbits for up to 10 weeks resulted in morphological changes of the vascular wall. Microscopic evaluation of the aorta revealed a lipid infiltration and an intimal thickening containing foam cells, which both became more pronounced as the cholesterol feeding was more prolonged. The intimal prostacyclin production showed a transient increase after 2 weeks, but was significantly decreased after 6 weeks of diet and remained at this low level during the rest of the experiment. No significant changes in formation of thromboxane B2 by the platelets could be observed, whereas the production of 12 HETE was enhanced. PMID- 3097760 TI - Platelet aggregation and thromboxane release induced by arachidonic acid, collagen, ADP and platelet-activating factor following low dose acetylsalicylic acid in man. AB - The present study was undertaken in order to characterize the dose-dependent nature of acetylsalicylic acid (ASA) on platelet aggregation and plasma thromboxane B2 (TXB2) release in healthy volunteers. Volunteers received either 25, 50, 100 or 500 mg daily for five consecutive days. At the end of the five day period, all dosages of ASA were capable of completely suppressing TXB2 production and arachidonic acid-induced platelet aggregation. At that time, the second phase of ADP-induced aggregation was also blocked. However, while the inhibition following 500 mg ASA was complete after 24 hours, total inhibition with 100, 50 and 25 mg was attained only after two, three and four days, respectively, indicating the cumulative effect of ASA on platelets. Aggregation induced by collagen was also inhibited dose-dependently- yet slower and at no time complete. ASA had no inhibitory effect on aggregation by platelet-activating factor (PAF). It is concluded that a daily dose of 50 mg ASA would suffice in blocking platelet TXA2 production and aggregation induced by most physiological agents. PMID- 3097761 TI - Relationship between cellular calcium and prostaglandin synthesis in cultured vascular smooth muscle cells. AB - We have investigated the effects of extracellular and intracellular Ca deficits and of pharmacologic agents thought to inhibit Ca influx or intracellular Ca mobilization on vasopressin-evoked changes of cytosolic Ca2+ levels and PG synthesis in cultured rat mesenteric arterial vascular smooth muscle cells. Vasopressin rapidly increased cytosolic Ca2+ as well as PG synthesis. The increase of cytosolic Ca2+ and the rate of PG synthesis were both maximal within the first minute of incubation. An extracellular Ca deficit of short duration partially inhibited both vasopressin-evoked PG synthesis and the increase of cytosolic Ca2+ by 40 to 60%. Two procedures which deplete cells of some of their intracellular Ca, namely a 30 min incubation in EGTA-supplemented, Ca-lacking media, or a 1 min incubation with ionophore A23187 in Ca-deficient media, decreased PG synthesis by 65% to 100%. The addition of extracellular Ca to Ca depleted cells restored the ability of vasopressin to stimulate PG synthesis. Two Ca channel antagonists, nifedipine or cinnarizine, had no effect on either vasopressin-evoked PG synthesis or increased cytosolic Ca2+, whereas TMB-8 (10 microM), a putative inhibitor of intracellular Ca mobilization, decreased PG synthesis by 75% by inhibiting acylhydrolase as well as cyclo-oxygenase activities, but had no effect on basal or vasopressin-evoked increase of cytosolic Ca2+, documenting that its inhibitory effect was not a consequence of decreased cytosolic Ca2+. These results demonstrate that decreased cellular Ca levels are associated with decreased cytosolic Ca2+ levels and PG synthesis, and support the hypothesis of a link between, on the one hand, cellular Ca and/or cytosolic Ca2+ and on the other hand, PG synthesis. PMID- 3097762 TI - Why are nursing diagnoses necessary? PMID- 3097763 TI - Radiation therapy of ovarian carcinoma: presentation of a six-field technique. AB - A new technique for radiotherapy in ovarian carcinoma is presented. The aim was to deliver a homogeneous radiation dose to the entire abdominal cavity. The whole abdomen, except for 20% of the upper compartment, received a homogeneous dose of 40 Gy, while 2/3 of the kidneys and the posterior part of the liver received a dose ranging from 40 to 20 Gy. No clinically significant impairment of liver function was seen during follow-up. PMID- 3097764 TI - [Leakage neutrons and X-rays in a therapeutic microtron facility]. AB - Measurements of dose equivalent rate distribution in a medical microtron facility were done for neutrons and X-rays originated from 14 MV or 8 MV X-ray irradiation by the microtron. Measured data are described with empirical formulas for convenience of quantitative reconstruction of the data. A formula consisting of a simple power function agrees well with measured data except for thermal neutrons, and is understood to describe the dose rate separating into the scattered and unscattered components in the case of the point source. The thermal neutron distribution in the maze is described with another formula of an exponential function. A discrepancy was observed between the X-ray distribution in the maze from 14 MV X-ray irradiation and that from 8 MV irradiation. This is estimated to be caused by a contribution of capture gamma-rays increasingly emitted in the case of 14 MV X-ray irradiation. PMID- 3097765 TI - [Acute pancreatitis associated with the use of sodium valproate]. PMID- 3097766 TI - [Basal pressure of the lower esophageal sphincter in Chagas' disease: megaesophagus and indeterminate form]. PMID- 3097767 TI - [Endocarditis caused by Candida albicans in a non-addicted person without previous cardiopathy]. PMID- 3097768 TI - [Enteral nutrition as preparation for high-risk surgery]. PMID- 3097769 TI - Measuring the oxygen cost of breathing in normal adults and patients with cystic fibrosis. AB - It has been suggested that the oxygen consumption of the respiratory muscles (VO2 resp) may play a role in limiting exercise performance in both healthy subjects and those with chronic airflow limitation (CAL). In order to measure VO2 resp reproducibly at both rest and on exercise, ventilation (VE) and total oxygen consumption (VO2) in 3 normal subjects and in 3 patients with cystic fibrosis were measured while breathing air and again when VE was stimulated by the addition of CO2 to the inspired gas. Since external work was the same it was assumed that any changes in VO2 would be due to the increase in VO2 resp during stimulated breathing allowing for the calculation of VO2 resp. The oxygen cost of breathing was higher in the patients with the increasing ventilation of exercise. These values were reproducible on repetitive measurements. It is concluded that the method employed is applicable in normal subjects and in patients with CAL, and that the O2 cost of breathing is higher in patients with CAL. The O2 cost of breathing increases as VE increases but even during exercise the VO2 resp is only a small fraction of the total VO2 and is unlikely to be a determining factor limiting exercise performance in either normal subjects or those with CAL. PMID- 3097770 TI - Phrenic nerve responses to hypoxia and CO2 in decerebrate dogs. AB - Phrenic responses to isocapnic hypoxia and hypercapnia were studied using paralyzed vagotomized dogs (either decerebrate or chloralose-anesthetized). The hypoxia-induced increase in phrenic minute activity (PMA) was significantly greater in anesthetized dogs when compared with the response observed in decerebrate dogs. Phrenic responses to hypercapnia were also significantly different in the two groups of dogs. Increases in phrenic amplitude (AMP) and frequency (FREQ) were observed in anesthetized dogs, whereas decerebrate dogs responded to CO2 without a change in FREQ. Spontaneously breathing dogs (either decerebrate or anesthetized) were used for studying the effects of vagotomy on the integrated phrenic neurogram. Changes in phrenic pattern in response to vagotomy were qualitatively similar in anesthetized and decerebrate dogs. However, in decerebrate dogs, AMP was disproportionately increased relative to the decrease in FREQ such that PMA increased following vagal transection. Conversely, in anesthetized dogs, the increase in AMP and decrease in FREQ in response to vagotomy were proportional; PMA remained unchanged. These results suggest that mesencephalic decerebration disrupts neuronal circuits which participate in the chemical control of breathing. In addition, suprapontine structures may be involved in coupling FREQ and AMP (tidal volume) so that PMA (ventilation) is stabilized. Finally, these studies provide evidence for a vagally-independent frequency controller in dogs which is sensitive to hypoxia and hypercapnia, but appears to be highly dependent upon suprapontine structures. PMID- 3097771 TI - Load compensation during positive pressure breathing in anesthetized man. AB - To investigate the mechanisms by which human subjects prevent or compensate for the change in respiratory muscle length imposed by applying continuous positive pressure to the airways, six men were studied under general anesthesia with methoxyflurane at the end of a minor surgical procedure (rhinoplasty). Ventilatory and occlusion pressure response to carbon dioxide was measured by a rebreathing technique with no bias pressure, or with 16 cm H2O positive pressure produced by adding weights to a spirometer bell. Static pressure-volume curves of the respiratory system were obtained while the subjects were paralyzed with succinyl choline. In contrast to awake subjects described in other studies, the anesthetized patients did not activate expiratory muscles to combat the rise in end-expiratory level caused by pressure, and showed little evidence of enhanced activation of inspiratory muscles that in the conscious state compensates for the disadvantage of their shorter length. A change in the shape of the occlusion pressure wave, however, suggested that positive pressure had some effect on the neural discharge to inspiratory muscles. The mechanisms by which the respiratory system defends itself against a pressure load that tends to change end-expiratory level are sensitive to anesthesia and may require consciousness. PMID- 3097772 TI - Intracellular pH regulation during prolonged hypoxia in rats. AB - Conscious rats maintained for three weeks at PB 370-380 Torr were studied in a chamber where PIO2 was maintained at 68-70 Torr at ambient barometric pressure (740-750 Torr). Controls were pair-fed rats maintained at ambient barometric pressure and studied at ambient PIO2 for 4 h. Steady-state intracellular pH (pHi) of left and right ventricle, and of tibialis anterior, quadriceps and diaphragm was determined from the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO). Apparent non-bicarbonate buffer value (beta app) was calculated as the ratio of the change in HCO3- concentration to the change in pH elicited by the increase in PCO2. beta app of plasma, tibialis anterior, quadriceps and diaphragm was approximately 2, 3, 6 and 12 times higher, respectively, in hypoxic than in normoxic rats. Neither left nor right ventricular beta app was significantly changed by prolonged hypoxia. In the hypoxic animals, bilateral nephrectomy abolished the increase in beta app of plasma, tibialis anterior and quadriceps, and moderated the increase in beta app of diaphragm. No significant effect of nephrectomy was observed in beta app of either left or right ventricle. The results indicate that in the skeletal muscles studied under conditions of an acid load in the form of increased PCO2, intracellular pH is better regulated in hypoxic than in normoxic rats. The effects of nephrectomy suggest that this is due, at least in part, to a more effective renal compensation in hypoxic than in normoxic rats. Prolonged hypoxia, on the other hand, does not affect the cell pH regulation of right or left ventricle. PMID- 3097773 TI - Renal compensation of hypercapnia in prolonged hypoxia. AB - We previously showed that rats made hypoxic for three weeks were able to regulate their plasma pH better than normoxic rats during acute hypercapnia. This improved pH regulation was abolished by nephrectomy, suggesting that it was due, at least in part, to a more effective renal compensation of hypercapnia in hypoxic rats. To test this possibility renal acid excretion was measured in conscious rats that had been kept at PB 370-380 Torr for three weeks. The rats were studied in a chamber where PIO2 was kept at 68-70 Torr at ambient PB (740-750 Torr). Controls were pair-fed normoxic rats. After a 2 h control period, inspired PCO2 was increased for 4 h. The apparent non-bicarbonate buffer value of arterial blood plasma was twice as high in the hypoxic than in the normoxic rats. Renal excretion of ammonium increased to a similar extent during hypercapnia in both normoxic and hypoxic rats. Titratable acid excretion of normoxic rats did not change significantly during hypercapnia. In the hypoxic rats, on the other hand, total excretion of titratable acid in the 2 h control period was 90.9 +/- 16.4 mumol/rat; and increased to 150.0 +/- 13.4 mumol/rat in the first 2 h and to 232.9 +/- 26.0 mumol/rat in the last 2 h of hypercapnia. In spite of this large increase in acid excretion, urine pH of hypoxic rats did not change significantly, indicating a higher buffer value of the urine of hypoxic rats. These results confirm our previous observations and support the idea that the improved pH regulation of hypoxic rats is due in part to a more effective renal compensation of hypercapnia. PMID- 3097774 TI - Hyperoxic ventilatory responses of high altitude acclimatized cats. AB - We have examined the effect of steady-state hyperoxia on the ventilation of sea level (SL) cats and cats acclimatized to simulated high altitude (HA) at 5500 m for three weeks. Three groups of cats were studied. In group I, the ventilatory responses to 10%, 21% and 100% O2 were studied at SL, and after acclimatization to HA, the ventilatory responses to 10% and 100% O2 were measured. In group II the ventilatory responses and femoral artery and superior sagittal sinus blood gases were measured in two sets of cats, one at SL and one at HA, during exposure to the gases outlined in group I. In group III, we examined the effect of chronic vagotomy on the ventilatory responses to the gas mixtures outlined in group I. Breathing 100% O2 at SL had no significant effect on ventilation, tidal volume, respiratory frequency, or cerebral blood flow (inferred from the cerebral veno arterial CO2 difference). Ventilation was constant in the HA acclimatized cats while breathing 10% and 100% O2, but the ventilatory pattern changed dramatically during hyperoxia: respiratory frequency increased and tidal volume fell. Breathing 100% O2 was associated with changes in CBF, and venous PCO2 that might be expected to stimulate ventilation, but the change in ventilatory pattern suggests to us that hyperoxic disinhibition of central respiratory processes (which were modified by HA acclimatization) is the mechanism whereby ventilation is sustained during hyperoxia at HA. After vagotomy at HA, ventilation remained constant while breathing 100% O2, but the changes in respiratory pattern were no longer apparent. Therefore, vagal afferents seems to have a role in determining the pattern, but not necessarily the absolute level, of ventilation during hyperoxia. Cats vagotomized at SL prior to HA exposure did not show any evidence of HA ventilatory acclimatization; thus, the vagi may also play a heretofore unrecognized role in the process of acclimatization. PMID- 3097775 TI - Ventilatory responses to hypoxia nullify hypoxic tracheal constriction in awake dogs. AB - Three awake dogs with chronic tracheostomies were used to study the effects of hypoxia (12% O2) on tracheal smooth muscle tone. Pressure changes within a water filled cuff in an isolated portion of the cervical trachea reflected changes in tracheal tone. During spontaneous ventilation, hypoxia produced hyperventilation, but no significant change in tracheal tone. If hypocapnia was prevented with inspired CO2 during hypoxia, one of three dogs increased tracheal tone, and all dogs increased ventilation beyond that measured with hypoxia alone. When the awake dogs were ventilated mechanically to prevent changes in ventilation, hypoxia always increased tracheal tone. We made independent changes in ventilation and CO2 similar to the spontaneous responses to hypoxia to test these effects on tracheal tone. When the dogs were ventilated mechanically first with 2% CO2, and then with no CO2, the resulting drop in end-tidal CO2 always decreased tone. When the tidal volume on the ventilator was increased under hyperoxic, isocapnic conditions, tracheal tone always decreased. We conclude that the normal ventilatory response to hypoxia opposes the bronchoconstrictor effect of hypoxia, resulting in no net change in tracheal smooth muscle tone. PMID- 3097776 TI - Sensitivity of avian intrapulmonary chemoreceptors to venous CO2 load. AB - To investigate the response of individual intrapulmonary chemoreceptors (IPC) to venous CO2 loads approximating moderate muscular exercise, we recorded vagal discharge from 33 IPC arising from the left lungs of 9 anesthetized, unidirectionally ventilated Pekin ducks. Each IPC was studied during control conditions (PECO2 = 29.0 +/- 0.8 Torr, PVCO2 = 30.2 +/- 0.6 Torr) and during venous CO2 load (PECO2 = 29.5 +/- 0.7 Torr, PVCO2 = 51.5 +/- 1.4 Torr). Venous loading was produced by increasing the percentage of CO2 in the gas ventilating the right lung from 0 to 9-25% CO2. The flow of 1% CO2 through the left lung was adjusted to keep the left lung PECO2 constant. During venous loading, discharge frequencies indicated that the PCO2 at the receptive sites fell, on the average, 1.6 +/- 0.8 Torr. PMID- 3097777 TI - [Levels of secretory IgA in the saliva of healthy children in Mexico City]. PMID- 3097778 TI - [Genetic heterogenicity study in Fanconi's anemia by the addition of plasma]. PMID- 3097779 TI - [Deep venous thrombosis in a patient with brucellosis and a probable lupoid inhibitor. Report of a case]. PMID- 3097780 TI - [The organization of thalamic connections]. AB - Connections ascending to the thalamus. Contrary to classical opinion, all thalamic nuclei receive extrathalamic afferents. Segregation or convergence within a topographically defined nucleus represent two modalities of thalamic afferents. In addition, certain topographically organized thalamic afferents possess "privileged" or primary "targets" in the thalamic nucleus while others possess supplementary "targets" in other thalamic nuclei (see cerebellar, pallidal and spinothalamic projections). Ascending connections from several brain stem structures can converge on the same nucleus or diverge to several thalamic nuclei. Thalamic connections with the telencephalon. Methods for determining axonal transport have demonstrated that all thalamic nuclei, with the exception of the reticular nucleus and the ventral part of the lateral geniculate body, project towards the cerebral cortex. Four nuclear complexes can be recognized in the cat as a function of the different modalities of localization, concentration and lamination of the projections towards the cortex and the central grey nuclei. In general, the thalamocortical connections have reciprocal ipsilateral corticothalamic projections originating in the infragranular layers of the cerebral cortex. The reticular nucleus and the ventral part of the lateral geniculate body, which is not projected to the cerebral cortex, are exceptions. Each cortical area receives a "privileged" connection from a thalamic nucleus and a supplementary connection- from one or several other thalamic nuclei. The "privileged" connections usually pass to the fourth and third layers of the neocortex, and sometimes also to the first layer. In contrast, the supplementary connections pass to different superficial or deep cortical layers. Each nucleus is formed of subunits which possess different hodologic and topographic characteristics as a function of the nucleus considered. Convergence or divergence of thalamocortical and corticothalamic projections on the different thalamic nuclei, as well as the laminar distribution of efferents in the cerebral cortex, are related strictly to the hodologic organization of different cellular subunits constituting the nuclei. Concentration or diffusion of thalamic projections on cerebral cortex is related more to the single or multiple projection of cell populations belonging to a thalamic nucleus than to widespread collateralization of thalamocortical axons. PMID- 3097782 TI - [The thalamus: motor functions]. AB - Thalamic nuclei constitute the diencephalic relay system between different afferent systems and the telencephalon. The "motor" thalamus links cerebellar and pallidal afferents with the motor and pre-motor cortical regions. Separation of pallido-thalamo-cortical and cerebello-thalamo-cortical pathways is relatively complete: afferents of pallidal origin are relayed by thalamic nuclei VA, VLo and VLm and are projected onto prefrontal and supplementary motor areas whereas afferents of cerebellar origin are relayed in the VL and VPLo and then projected onto motor areas 4.6 and parietal areas 5 and 7. This report is concerned mainly with the analysis of the motor thalamus as a relay system for afferents of cerebellar origin. The anatomofunctional organization of the cerebello-thalamo cortical tract possesses a topographic arrangement and also wide convergences and appears able to participate in the realization, through the motor cortex, of motor synergies and of co-ordinating postures and movements. The cerebello cortical tract apparently plays a different role during learning of a movement and executing an automatized movement. For the latter, it is involved in their onset and in their completion. Its contribution to fine control of temporal parameters of motor commands or control of peripheral afferent messages is not decisive. During learning of a movement the cerebello-cortical tract plays a predominant role. According to Ito, the cerebellum is involved in the process of automatization of a movement, organized initially entirely by the cortex and then becoming progressively subcortical. Plasticity of cerebellar microcircuits could be the basis for these automatization processes expressed through the cerebello thalamo-cortical tract. PMID- 3097781 TI - Specific somatic sensory relays in the mammalian diencephalon. AB - There are five major domains within the diencephalon that receive input from ascending somatic sensory pathways serving the limbs, trunk and viscera. These domains include the ventroposterolateral nucleus (VPL), the posterior group complex (PO), the zona incerta (ZI), the intralaminar complex and the thalamic reticular nucleus. Of these five domains, VPL is commonly considered a "specific" somatic "relay". The reasons for this view are that VPL receives dense, synaptically secure and precisely organized input from the equally precisely organized dorsal column nuclei (DCN), that most of VPL's neurons have small, unimodal cutaneous receptive fields which reflect their input from DCN, and that these neurons project this information in a precise way to the somatic sensory cortex. Several lines of evidence suggest that this rather simple view of VPL be modified. First, not only does VPL receive complex patterns of partially converging input from other ascending somatic pathways besides the DCN, but the pattern of its input from DCN appears to be more complex than once thought. Second, such input convergence and complex connective patterns also occur within PO and ZI (although the characteristics of the patterns differ between the three domains). Third, the response properties of neurons within VPL differ in its different parts and are not necessarily precise mirrors of the response properties of neurons within DCN. Fourth, although the responses of neurons in PO on the whole differ from those in VPL, there are some similarities. The same conclusion may prove true for neurons in the DCN-recipient portion of ZI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097783 TI - [Place of the thalamus in the network of interconnections between the association and limbic cortices in the monkey]. AB - Anatomophysiological criteria underlying the definition of associative cortex as well as limbic cortex include some imprecise data. The original notion of "cortical association spheres" (Flechsig) with no connections with the thalamus has rightly been abandoned, and that of the macroscopic "large limbic lobe" (Broca) fails to stand up to histologic or hodologic findings. However, the concept of cortical areas implicated specifically in multiple sensorial integration, sensory-motor coupling and control of behavior lasts due to necessity. In the monkey, the posterior parietal cortex of area 7 (PG area), the cortex of the upper slope of the superior temporal sulcus (STS) and the prefrontal cortex anterior to the sulcus arcuatus exchange direct corticocortical connections, receive afferents from sensory cortex and are not connected to specific thalamic relays. The term "associative" in its widest sense applies more particularly therefore to these cortical areas organized in networks. On the internal surface of the hemisphere, the cingular gyrus, retrosplenial cortex and parahippocampic gyrus (TF and TH areas) which occupy the major part of the limbic lobe, participate in the formation of this network and exchange direct cortico cortical connections with the associative cortex defined above. The use of anterograde (labelled aminoacids) and retrograde (peroxidases) markers and of fluorescent dyes, allowing double retrograde labelling, demonstrates that the median pulvinar nucleus is connected with the knots of the associative cortical network. This thalamic nucleus, of a relatively increased size from phylogenetic evolution, is therefore excluded from the classification opposing specific and diffuse projection nuclei. In contrast to the thalamic reticular nucleus, which lacks cortical projections, and to the nuclei of the internal medullary band, which have the striatum as main target, the median pulvinar is a thalamic structure connected directly and specifically with each of the cortical areas, lesions of which result in negligence behavior. PMID- 3097784 TI - [Memory disorders in lesions of the thalamus in man]. AB - Isolated memory disorders occur after bilateral involvement of thalamus. Anterograde amnesia is not complete; retrograde amnesia is always severe. Four groups of thalamic nuclei may be affected: anterior nuclei; midline nuclei, medialis dorsalis nuclei; intralaminar nuclei. A pathophysiologic interpretation is proposed. Three kinds of memory processes may be involved: consolidating process that leads to the formation of memory traces (anterior nuclei, midline nuclei); retrieving process that leads to the activation of memory traces (intralaminar nuclei); temporal organizing process that regards ancient et recent memory traces (medialis dorsalis nuclei). PMID- 3097785 TI - [Use of carbon dioxide gas to treat osteoarthrosis deformans]. PMID- 3097786 TI - Clinical manifestations and therapy of Lactobacillus endocarditis: report of a case and review of the literature. AB - A case of Lactobacillus casei endocarditis that occurred on a Carpentier-Edwards porcine valve is reported. A review of the literature, which yielded 23 other reports of endocarditis due to this organism, suggests that Lactobacillus is a rare cause of endocarditis. Typically, it occurs in a patient with preexisting structural heart disease (20 of 24 [83%]) and often with some form of recent dental infection or manipulation (18 of 24 [75%]). Six (25%) of 24 patients died of this infection; however, only one (5%) of 19 who were treated with adequate antimicrobial therapy died. The response to antimicrobial therapy was better in the more recent cases. Of those 18 patients who completed a full course of therapy, seven (39%) experienced a relapse; five of these were cured of their infection with a second course of antimicrobial therapy, which usually included higher doses of intravenous penicillin. Our case represents the second reported case that required surgical intervention for cure. Embolic phenomena occurred in 10 (42%) of 24 cases. Various combinations of antibiotics have been successful in achieving cure; however, at present, high-dose penicillin (greater than 25 million units/day) in combination with an aminoglycoside for a period of six weeks appears to be the optimum therapy. PMID- 3097787 TI - [Activity of combinations of antibacterial agents on Pseudomonas aeruginosa strains]. PMID- 3097788 TI - The specificity of human autoantibodies to IgG: the development of methodology for measuring the specificity of antiglobulin isotypes in rheumatoid and normal sera. AB - A simple enzyme-linked immunosorbent assay (ELISA) inhibition test was devised to determine the separate specificities for rabbit IgG, Fc, and Fab fragments of IgM, IgG, and IgA antiglobulins in sera obtained from rheumatoid and normal individuals. Results of this test showed that most of the anti-rabbit IgG activity present in the three immunoglobulin (Ig) isotype preparations from a rheumatoid serum was specific for the Fc portion of whole IgG. Some anti-Fab activity was detectable in all three Ig isotypes examined, but this had much less avidity and/or specificity than the anti-Fc activity. In contrast, normal antiglobulins of M and G classes were mostly specific for the Fab region of rabbit Ig, although a small but measurable amount of Fc-specific antiglobulin was present and was of high relative avidity. The low normal serum IgA anti-IgG activity detected was essentially nonspecific. We conclude that normal antiglobulins differ from "rheumatoid factors" in their specificity and that this may relate to different roles in health and disease. PMID- 3097790 TI - Cryoglobulins and infectious diseases. AB - The relationship between infectious diseases due to various pathogenetic factors and cryoglobulin production mechanisms has been investigated. Cryoglobulins have been evidenced in infections caused by very heterogeneous pathogens, i.e. leptospirosis, psittacosis, Mediterranean tick typhus, brucellosis, gram-negative bacterial septicemias, in which they had never been previously reported. In type A hepatitis a high cryoglobulin prevalence (91%) has been confirmed during the acute phase, with a rapid decrease both in prevalence and concentration in the subsequent stages of the disease. Cryoglobulins were all of type III and were mainly represented by IgM; anti-HAV-IgM antibodies have been evidenced in all but one cryoprecipitates. In non-A, non-B hepatitis a lower cryoglobulin prevalence (44.7%) was shown during the acute phase and the same fast decrease has been noted in the subsequent stages. Cryoglobulins were all of type III and in some cases polyclonal IgG was the only Ig class present in cryoprecipitates. The cryoglobulin prevalence in the acute phase of HBsAg-positive hepatitis amounted to 73.4%; all the cryoprecipitates were of type III. No correlation between the presence of cryoglobulins and HBeAg positivity or between cryoglobulins and delta agent infections was found. In all the cases studied the presence of cryoglobulins was related to the persistence of liver damage. Cryoglobulins were not found in HBsAg chronic carriers, while they have been evidenced, by a preliminary study, in 41.6% of HTLV-III antibody-positive subjects complaining of a persistent generalized lymphadenopathy without clinical or laboratory signs of liver impairment. No HTLV-III antibodies were found by ELISA method in the type III cryoprecipitates. PMID- 3097789 TI - Cryoglobulins and pyroglobulins: an overview. AB - Cryoglobulins are serum proteins with heterogeneous etiopathogenetic and immunochemical properties. What they have in common is temperature-dependent insolubility, in that at temperatures below 37 degrees C (often around 4 degrees C) they precipitate, and then redissolve at 37 degrees C. When the etiopathogenesis of the cryoglobulinemia is unknown, which is true for many patients, the condition is called idiopathic or essential cryoglobulinemia, whereas it is termed secondary whenever it appears to be associated with one of several diseases. Cryoglobulinemia has indeed been found in patients with lymphoproliferative and autoimmune disorders, liver diseases, infectious (viral, bacterial, fungal and parasitic) diseases, and so on. Cryoglobulins are usually classified according to their immunochemical properties as single-type monoclonal, mixtures of a monoclonal Ig with non-immunoglobulin material (DNA, lipoprotein, complement), mixed with one monoclonal Ig or mixed polyclonal, in which constitutive Ig fractions are polyclonal. As compared with normal Ig, cryoimmunoglobulins have sometimes been found to exhibit a peculiar amino acid structure of their heavy chains, less often of their light chains as well, and to have a lower carbohydrate content. Such structural abnormalities may contribute to their loss of solubility at low temperatures, possibly associated to the steric changes induced by the low temperature, causing the precipitate to form. The most common clinical features of cryoglobulins are correlated with vasculitis in the various organs and sometimes with increased viscosity of the plasma. Signs and symptoms include purpura, ulcers of the extremities, arthralgia, proteinuria, hepatic damage, abdominal pain, congestive heart failure, mental confusion, oligo anuria, hemorrhagic diathesis, and coma. Pyroglobulins are also serum proteins with temperature-dependent insolubility. However, although they precipitate out of serum heated at 56 degrees C for half an hour, they do not resolubilize when the serum is returned to 37 degrees C. Pyroglobulins have been mainly found in patients with lymphoproliferative diseases (especially Waldenstrom's macroglobulinemia, with or without cryoglobulinemia), systemic lupus erythematosus, and neoplasia. So far, only single monoclonal IgG, IgM or IgA pyroglobulins have been described. Since they precipitate only at 56 degrees C, pyroglobulins do not cause clinical symptoms and they are usually discovered by chance. PMID- 3097791 TI - [Vocabulary for the records]. PMID- 3097792 TI - [Programming and updating the National Health Service]. PMID- 3097793 TI - [Educational needs and organization of updating courses]. PMID- 3097794 TI - [How to organize the initiative for modernization on the level of a department or service]. PMID- 3097795 TI - [A course on hospital infections]. PMID- 3097796 TI - [Continuing training of nursing personnel: analysis of educational needs]. PMID- 3097797 TI - [Retraining and learning processes]. PMID- 3097798 TI - [Vademecum for personnel updating. What to choose, how, and for whom]. PMID- 3097800 TI - False epidemiological results from the bulk transport of dried filter papers in urinary schistosomiasis. AB - In field studies in Schistosoma haematobium endemic areas, dried filters must be transported in bulk to central laboratories, either for primary screening and counting, or for quality control of field workers. We examined filters before and after bulk transport, from three populations, of high, medium and low prevalence rate. A total of 312 filters were examined before and after transport; 28.6% of all eggs on filters were lost during transport. Negative filters became positive during transport, and hence false prevalence rates resulted from after transport studies. Egg loss did not seem to be related to initial egg density. The operational results of these findings could be serious, in terms of distribution of treatment and evaluation of results and costs. PMID- 3097799 TI - Studies on the mechanisms by which tumor promoters stimulate the growth of primary neonatal rat hepatocytes. AB - A single exposure to a low concentration (10(-10) mol/L) of several tumor promoters, namely 12-O-tetradecanoylphorbol-13-acetate (TPA), phenobarbital (PB), nafenopin, saccharin, teleocidin, benzoyl peroxide, butylated hydroxytoluene (BHT), dichlorodiphenyltrichloroethane (DDT), lindane, clofibrate, and melittin significantly stimulated DNA synthesis of neonatal rat hepatocytes in 4-day-old primary cultures. These cultures were kept in low-calcium (0.01 mmol/L) HiWoBa2000 synthetic medium, thereby evoking a neoplastic phenotype in otherwise normal (i.e., non-initiated) cells. The simultaneous addition of a single dose of alpha-tocopherol (10(-4) mol/L) or selenous acid (10(-5) mol/L), just as that of exogenous superoxide dismutase (SOD) (4), together with each of the above agents fully suppressed the stimulation of hepatocytic DNA synthesis by the xenobiotics. Hence, these findings strengthen the view that superoxide anions (or some other oxidizing compounds) act as the common mediators of the mitogenic effects of various tumor promoters in hepatocytes. Inhibition kinetics studies, in which TPA in a single dose (10(-10) mol/L) was used as the paradigmatic compound together with several kinds of inhibitors of its activity showed that the early mitogenic effects of TPA, i.e., the commitment of quiescent (G0) hepatocytes and the reentry into active cycling of hepatocytes spontaneously poised at the G1/S boundary, required oxidizing compounds, arachidonate metabolism derivatives, and plasmalemmal calcium-binding sites and transmembrane calcium fluxes. Instead, a later TPAs effect, the flow into DNA synthesis of hepatocytes previously committed to cycle, was shown to be controlled by retinoid-modulable activities, by some product(s) of the lipoxygenase pathway, and again by plasmalemmal calcium binding sites and transmembrane calcium fluxes. Such results reveal that in the neonatal rat hepatocyte the ability to answer to a single mitogenic stimulus and the metabolic pathways by which this answer is enacted depend upon the mitotic cycle setting of the hepatocytes at the moment of the experimental treatment. PMID- 3097801 TI - Leukemia: when white cells run wild. PMID- 3097802 TI - How to make a feeding tube go down easily. PMID- 3097803 TI - [Residue levels of polychlorinated biphenyls in edible fish livers]. PMID- 3097804 TI - [Behavior of the blood forms of Trypanosoma cruzi obtained from mice used as biological filters, in culture and in triatomide]. PMID- 3097805 TI - [Comparative study of the behavior of infection in mice, through subcutaneous and intraperitoneal inoculation, using 2 strains of Trypanosoma cruzi]. PMID- 3097806 TI - Co-expression of surface immunoglobulin and T3 on hairy cells. AB - Whereas it is generally believed that most cases of hairy cell leukaemia (HCL) represent B cell neoplasms, it is reported here that 4 of 14 cases of HCL not only express monotypic surface immunoglobulin (SIg) but also react with the T cell-specific monoclonal antibody (Mab) UCHT1 by indirect immunofluorescence or immunoperoxidase staining. Although both UCHT1 and OKT3 recognize the T3 molecule, which is expressed in all normal T cells, UCHT1+ hairy cells (HCs) were consistently OKT3-. Spurious reactivity of UCHT1 antibodies with SIg+ HCs was excluded by showing that lymphocytes sensitized with an irrelevant mouse Mab did not stain with second layer antibodies and lymphocytes sensitized with second layer antibodies alone were always completely unreactive. Moreover, in 1 case the determinants demonstrable by both UCHT1 and anti-Ig were strongly re-expressed after capping and shedding, i.e. appeared to be endogenous. It is concluded that HCs with a hybrid T-B surface phenotype are more common than hitherto reported, that HCs may express T3 molecules as well as SIg but that determinants recognized by OKT3 may be cryptic or buried in the HC membrane. PMID- 3097808 TI - Thrombocytopenia and pseudothrombocytopenia: a clinical and laboratory problem. AB - During a 4-month period, the patients with thrombocytopenia (N = 14) at a haematological outpatient clinic were subjected to a special laboratory investigation. Evidence of pseudothrombocytopenia was found in 5 of the patients. 1 patient with a giant platelet syndrome associated with deficient platelet function was also found. It is concluded that pseudothrombocytopenia and various thrombocytopathies provide a significant confounding factor in the management of patients with alleged thrombocytopenia. It is therefore suggested that the initial diagnostic work-up of alleged thrombocytopenia patients should include an assessment of platelet morphology in addition to an overall haemostatic test (bleeding time) and platelet function tests. PMID- 3097807 TI - The effect of alpha and gamma-interferon on proliferation and production of IgE and beta 2-microglobulin in the human myeloma cell line U-266 and in an alpha interferon resistant U-266 subline. AB - An IFN-resistant subline (U-266r alpha) was established from the IFN-alpha sensitive myeloma cell line U-266 by subculturing U-266 cells with increasing doses of INF-alpha. The U-266r alpha secreted IgE at a higher rate than the U-266 (7.2 X 10(-13) g/c/8 h as compared to 3.3 X 10(-13) g/c/8 h). The 2 cell lines were found to be equally high producers of beta 2m (9.2 and 9.6 X 10(-13) g/c/8 h). The U-266 produced 2.9 times less IgE and 5 times more beta 2m compared to the initial production rates at establishment. INF-alpha and recombinant IFN alpha 2 (rIFN-alpha 2) inhibited proliferation and concomitantly decreased the rate of IgE and beta 2m secretion in U-266 but not in U-266 IFNr alpha, which in contrast was slightly stimulated by IFN-alpha with respect to growth, IgE and beta 2m secretion. In addition, IFN-alpha at a concentration of 100 U/ml was shown to decrease the IgE and beta 2m production without exerting more than minimal cytotoxicity on U-266 cells. No antiproliferative effect was found for IFN-gamma or recombinant IFN-gamma (rIFN-gamma) on either of the 2 cell lines. IFN-gamma and rIFN-gamma were, however, found to stimulate the production of beta 2m. Our results show that the U-266 and the derived IFN-alpha-resistant subline can be used as models for studying some of the biological effects of IFN-alpha and -gamma in vitro. The clinical implications of these in vitro results, in particular the usefulness of serum determinations of immunoglobulin and beta 2m concentrations for monitoring the tumor cell mass, are discussed. PMID- 3097809 TI - Partial response of meningeal myeloma to craniospinal radiotherapy. AB - Concomitant occurrence of meningeal involvement and thoracic plasmacytoma was observed in a patient with IgA lambda myeloma. Cerebrospinal fluid analysis revealed IgA-lambda paraprotein and pathological plasma cells. CT scan of the chest and lumbar myelogram excluded spinal cord compression. The patient partially responded to craniospinal irradiation but succumbed to rapidly progressive myeloma 20 weeks following diagnosis of meningeal involvement. PMID- 3097810 TI - Flow cytometric analysis of lymphocyte subsets in the bronchoalveolar lavage fluid and peripheral blood of healthy volunteers. AB - The lymphocyte subsets in the bronchoalveolar lavage fluid (BALF) and the peripheral blood of 25 healthy volunteers were examined by analysis with a fluorescence-activated cell sorter. Comparison of the lymphocyte subsets in the BALF with those of the peripheral blood revealed much higher values for the ratios of each Leu 3a+ (CD4), Leu 3+8-, and Leu 2+15- cells, while the ratios of Leu 1+ (CD5), Leu 2a+ (CD8), Leu 7+, Leu 8+, Leu 10+, Leu 11a+ (CD16), Leu 12+, and Leu 2+15+ cells were low in the BALF. The above results indicate that the lymphocyte subsets in the BALF from healthy individuals are mainly composed of cells with surface phenotypes of helper T cells and cytotoxic T cells with virtual absence of cells carrying suppressor T and NK cell phenotypes, and with low B cell ratio. Therefore, it is assumed that the local immune mechanism of the lung is different from that of the peripheral blood. PMID- 3097811 TI - Serum and plasma fibronectin binds to complement reacted immune complexes primarily via Clq. AB - The binding of fibronectin to human Clq, C3b, and complement-reacted immune complexes (IC) was investigated by enzyme-linked immunosorbent assays. Microplates were coated with BSA followed by incubation with rabbit-anti-BSA IgG or F(ab')2 fragments of rabbit anti-BSA. Incubation of the solid phase with serum at 37 degrees C caused attachment of Clq and C3b. Addition of EDTA to the serum inhibited the binding of C3b, but not Clq, whereas substitution of the anti-BSA IgG on the solid phase with the F(ab')2 fragments abrogated the Clq, but not the C3b binding. Fibronectin binding was observed after incubation of the solid-phase IC with serum or plasma at conditions where Clq was also bound, whereas only minor amounts of fibronectin bound to the solid phase IC via C3b. Purified fibronectin showed a dose-dependent binding to solid-phase IC pretreated with Clq or fibronectin-depleted serum, confirming that the binding of fibronectin to IC largely occurred via Clq. Significantly smaller amounts of fibronectin were bound to solid-phase IC incubated with plasma instead of serum, despite the higher fibronectin concentration in plasma. This difference was found not to be due to a fibrinogen-fibronectin interaction in plasma. Binding of fibronectin to preformed fluid phase IC incubated with serum was demonstrated by SDS-PAGE analysis of PEG precipitated IC. PMID- 3097812 TI - Lymphocyte activation and induction of interferon gamma in human leucocyte cultures by the mitogen in Mycoplasma arthritidis supernatant (MAS). AB - This report succinctly summarizes a number of experiments in which human leucocytes were activated by the mitogen in the supernatant of cultured Mycoplasma arthritidis (MAS). Lymphocytes from a large number of donors were found to be reactive when the two parameters of lymphoproliferation and of production of gamma interferon were analysed. Lymphocytes of cord blood origin were also reactive in lymphoproliferation. Their interferon production was low, but this has been established previously for mitogens in general. During the course of the studies, different batches of MAS were tested, including most recently a purified preparation. All of these were active. Removal of accessory cells adherent to nylon wool column abolished MAS reactivity, whereas it has little effect on lymphoproliferation induced by phytohaemagglutinin (PHA). MAS reactivity was also strongly reduced when monoclonal anti-HLA-DR antibodies were added to the leucocyte cultures. PMID- 3097813 TI - Some effects of treatment with ethinyl oestradiol with or without polyoestradiol phosphate in patients with prostatic carcinoma. AB - Eleven patients with prostatic carcinoma were treated with ethinyl oestradiol (Etivex) 50 micrograms three times daily with and 10 patients without 80 mg polyoestradiol phosphate (Estradurin) monthly. Both forms of treatment produced a significant decrease in the serum testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) and a significant increase in the testosterone oestradiol-binding globuline (TeBg). Serum prolactin was significantly higher at 1, 3 and 6 months after treatment, in all patients studied, but the concentrations found at 12 and 18 months did not differ from those before treatment. One out of 10 patients treated with ethinyl oestradiol had congestive heart failure. Five out of 11 patients treated with ethinyl oestradiol polyoestradiol phosphate had cardiovascular or liver complications. Three of the 5 had thromboembolic complications. It is concluded that ethinyl oestradiol given in combination with polyoestradiol phosphate, was not superior in decreasing serum testosterone when compared to ethinyl oestradiol given alone. Furthermore, the oestrogens used, elevated prolactin only, during the first 6 months of treatment. There were fewer complications using ethinyl oestradiol alone than when using ethinyl oestradiol combined with polyoestradiol phosphate. PMID- 3097814 TI - [Food allergies. III. Therapy: elimination diet, symptomatic drug prophylaxis and specific hyposensitization]. AB - The treatment of food allergies is logically based on strict elimination of causative allergens. While it is easy to eliminate food which is infrequently consumed, it is more difficult to manage an allergy involving regularly consumed foods, especially where patients have to eat away from home for professional reasons. The creation of elimination diets for milk, eggs, and mould and yeast allergies is discussed. In raw food and vegetable allergy the act of cooking is often sufficient to denature the allergen as it is unstable to heat. Follow-up investigations show that some 50% of children achieve cure spontaneously by strict elimination diet, especially in regard to milk allergy. In our own 173 (mainly adult) patients with food allergy, some 2/3 reported after 3-5 years that a strict elimination diet had to be followed, since otherwise prompt relapse of allergic symptoms was noted. About 1/3 of patients, mainly with milk, cheese or egg allergy, can hope for spontaneous desensitization by appropriate diet. This is demonstrated by a case history with disappearance of IgE antibodies. Should this fail to occur, oral desensitization with milk or egg-white extracts offers an effective therapy. The practice of hyposensitization with foodstuffs is illustrated by examples and tabulation of immunologic parameters. In raw food or vegetable allergy, which is often associated with birch or mugwort pollinosis, improvement or even complete cure can be expected in about 1/3 of cases by systematic desensitization of pollinosis. On the other hand, the therapy and prognosis of food allergy involving extreme and polyvalent sensitivities, especially to spices, or with multifactorially induced symptoms, is more problematic. In these cases a strict elimination diet should be followed by continuous prophylactic/symptomatic treatment with antianaphylactic substances such as cromoglicinic acid (Nalcrom) - especially in gastrointestinal food allergies - or with ketotifen (Zaditen) or oxatomide (Tinset) in hematogenically released shock fragments. Patients with severe anaphylactic reactions after meals should, by analogy with patients with hymenoptera allergy, carry an emergency kit containing an adrenaline spray (Medihaler-Epi), a soluble corticosteroid (e.g. Betnesol) and anthistaminic drugs (e.g. Tavegyl, Teldane). PMID- 3097815 TI - [Syncope in a 16-year-old young man during a football match]. AB - A case is reported of a previously healthy 16-year-old boy who developed a rapid atrial fibrillation following a minor thoracic impact. This tachyarrhythmia resistant to several drugs responded immediately to administration of flecainide. The restoration of sinus rhythm led to diagnosis of type A Wolff-Parkinson-White syndrome. PMID- 3097816 TI - [Food allergies. III. Therapy: elimination diet, symptomatic medical prevention and specific hyposensitization]. PMID- 3097817 TI - [A new test for evaluating the von Willebrand factor: collagen-induced agglutination of fixed thrombocytes]. AB - In primary hemostasis von Willebrand factor (vWf) promotes the adhesion of platelets to subendothelial structures of the damaged blood vessel. A new test is described which measures the collagen binding affinity of vWf. Activities of vWf in plasmas of 51 patients were measured with either collagen (ColCof) or ristocetin (RCof). Regression-analysis showed a good correlation of both activities (r = 0.924). In a second group of 21 patients with a variant of von Willebrand's disease, ColCof activity was generally higher than RCof activity. PMID- 3097818 TI - [Binding of the von Willebrand factor to solid surfaces: effect of shear strength]. AB - Platelet adhesion onto subendothelium of a damaged blood vessel depends upon the presence of von Willebrand factor (vWf) only at high flow shear rate. Our results showed enhanced adsorption of vWf onto stainless steel and latex surfaces under conditions of high shear stress, thus suggesting that in the rapidly flowing blood the extremely long vWf molecules are stretched, thus accelerating their binding to a given surface. PMID- 3097819 TI - [Detection of blood coagulation inhibitors using a modified Lossing-Kasper test]. AB - Inhibitors, particularly against factor VIII or IX, are generally determined by the Bethesda method, which is time-consuming and of moderate sensitivity. Since the residual factor VIII/IX activity in a mixture of patient's and normal plasma is only measured after incubation, it provides no information on the kinetics of inactivation. Whereas a protracted inhibitory activity is observed in haemophiliacs after replacement therapy (isoantibodies) as well as in acquired haemophilia (autoantibodies), immediate inhibition is characteristic of antibodies directed against phospholipids. For clinical and therapeutic reasons it would be necessary to discriminate between these two kinds of inhibitor. Our modification of the Lossing & Kasper screening test eliminates these disadvantages: it is highly sensitive (patient's and normal plasma are mixed at a 4:1 ratio), easy to perform (aPTT system), and comparison of the tests with plasmas mixed before and after incubation makes it possible to distinguish between fast and slow inhibitors. The highly reproducible test is performed as follows: 0.4 ml of patient's plasma is added to tube 1 (T1), 0.4 ml of normal pooled plasma to tube 2 (T2) and a mixture of 4 parts patient's and 1 part normal plasma to tube 3(T3). After incubation (2 hrs, 37 degrees C) patient's and normal plasmas incubated separately are mixed at a 4:1 ratio (T1+2). aPTTs are performed with T1+2 and T3, using a chloroform brain extract diluted 1:400 and supplemented with kaolin 2 mg per ml of diluted chloroform brain extract. In the absence of an inhibitor aPTTs are in the region of 70 sec.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097821 TI - A new look at an old fossil face. PMID- 3097820 TI - [EDTA-dependent pseudo-thrombopenia]. AB - Pseudothrombocytopenia, a term used to define a spuriously low platelet count produced by automatic cell counters, is most often due to platelet clumping induced by EDTA. In a period of two years we have observed 8 patients with a mean platelet count of 46,000/mm3 in the presence of EDTA. When samples of capillary blood (without EDTA) were tested, the mean platelet count was 202,000/mm3. A further patient had platelet adherence to neutrophils with normal platelet counts. This rare finding can also lead to pseudothrombocytopenia. In the event of unexpected thrombocytopenia a smear from EDTA-blood samples reveals the presence of platelet clumping or adherence to neutrophils. Counts of capillary blood samples reveal the true platelet number. PMID- 3097822 TI - The hypogonadal mouse: reproductive functions restored by gene therapy. AB - The hypogonadal (hpg) mouse lacks a complete gonadotropin-releasing hormone (GnRH) gene and consequently cannot reproduce. Introduction of an intact GnRH gene into the genome of these mutant mice resulted in complete reversal of the hypogonadal phenotype. Transgenic hpg/hpg homozygotes of both sexes were capable of mating and producing offspring. Pituitary and serum concentrations of luteinizing hormone, follicle-stimulating hormone, and prolactin were restored to those of normal animals. Immunocytochemistry and in situ hybridization showed that GnRH expression was restored in the appropriate hypothalamic neurons of the transgenic hpg animals, an indication of neural-specific expression of the introduced gene. PMID- 3097823 TI - Tumor necrosis factor reduces c-myc expression and cooperates with interferon gamma in HeLa cells. AB - The suppression of the c-myc nuclear oncogene is associated with growth arrest and may therefore be directly controlled by naturally occurring growth inhibitors. The effect of tumor necrosis factor (TNF) and of interferon-gamma (IFN-gamma) on c-myc expression was investigated in HeLa cells, which respond to these cytokines by a specific arrest in the G0/G1 phase of the cell cycle. Northern blot and nuclear transcription analyses indicated that each cytokine reduced within 1 to 3 hours the c-myc messenger RNA levels as a result of transcriptional inhibition. Adding the two cytokines together at saturating levels resulted in enhanced inhibition of c-myc transcription and of the c-myc messenger RNA steady-state levels. While the reduction of c-myc messenger RNA by IFN-gamma was dependent on new protein synthesis, the inhibitory effect of TNF on c-myc messenger RNA was direct and was not abrogated by cycloheximide. The differential effect of the protein synthesis inhibitor and the cooperative inhibitory effects of the two cytokines when added together suggest that IFN gamma and TNF reduce c-myc transcription through different molecular mechanisms. PMID- 3097824 TI - Role of phycoerythrin in marine picoplankton Synechococcus spp. PMID- 3097825 TI - Thyroid hormone induction of an autocrine growth factor secreted by pituitary tumor cells. AB - Thyroid hormones stimulate the rate of cell division by poorly understood mechanisms. The possibility that thyroid hormones increase cell growth by stimulating secretion of a growth factor was investigated. Thyroid hormones are nearly an absolute requirement for the division of GH4C1 rat pituitary tumor cells plated at low density. Conditioned media from cells grown with or without L triiodothyronine (T3) were treated with an ion exchange resin to remove T3 and were tested for ability to stimulate the division of GH4C1 cells. Conditioned medium from T3-treated cells was as active as thyroid hormone at promoting GH4C1 cell growth but did not elicit other thyroid hormone responses, induction of growth hormone, and down-regulation of thyrotropin-releasing hormone receptors, as effectively as T3 did. A substance or substances associated with T3-induced growth stimulatory activity migrated at high molecular weight at neutral pH and was different from known growth-promoting hormones induced by T3. The results demonstrate that thyroid hormones stimulate the division of GH4C1 pituitary cells by stimulating the secretion of an autocrine growth factor. PMID- 3097827 TI - Thrombin stimulates arachidonate metabolism in murine tumor cells. PMID- 3097826 TI - Modulation of smooth muscle responses by serine proteases and related enzymes. AB - Standard isolated smooth muscle tissue preparations were used to screen the musculotropic actions of serine proteases and other substances that are generated during hemostatic activation. Sera obtained from human, rabbit, and guinea pigs produced a dose-dependent contraction of these isolated tissue preparations. These sera also augmented the actions of epinephrine and other agonists on different tissue preparations. Both contractile and relaxant actions of proteases were observed with various serine proteases and their complexes. Thrombins (alpha, beta, and gamma) produced varying degrees of contractile actions of rabbit aortic strips; however, Factor Xa produced a marked relaxation of this preparation. Trypsin and kallikrein did not produce any action on the aortic strip and thrombin, however, produced contraction of the guinea pig ileum. Protease complexes produced varying musculotropic actions on the isolated tissue preparations, which may be related to their composition. The musculotropic actions of serum and thrombin were not blocked by conventional pharmacologic antagonists. However, protease inhibitors, such as hirudin, D-Phe-Pro-Arginal, and other derivatives, produced varying effects of the musculotropic actions of serum and thrombins. These results indicate that thrombin and related proteases generated during the activation of the hemostatic system are capable of producing direct musculotropic actions of various smooth muscles. Various serine proteases and serine protease complexes were found to produce strong hemodynamic effects in a rabbit model for the study of blood plasma. The smooth muscle modulant actions of serine proteases should be taken into account to clarify the vascular pathologic changes in relation to spasmogenic and spasmolytic syndromes observed during hemostasis disorders. PMID- 3097828 TI - The mucopolysaccharidoses and related conditions. PMID- 3097830 TI - [Enteral feeding]. PMID- 3097829 TI - [Pyrimidine nucleotide biosynthesis and 5-fluorouracil metabolism in DMBA-induced tongue carcinoma]. PMID- 3097831 TI - Symposium: Bioethical issues in organ transplantation. PMID- 3097832 TI - Detection of surface antigen in Rickettsia tsutsugamushi infected mouse reticuloendothelial cells. AB - Antibody produced by immunizing CBA/CaJ mice with RE cells from C57B1/6J mice infected 14 days earlier with R. tsutsugamushi Gilliam strain bound readily to Gilliam strain non-cell associated rickettsiae and less readily to the periphery of infected RE cells. Conversely, antibody produced by immunizing with RE cells infected 21 days earlier did not bind to Gilliam rickettsiae but bound to the surface of RE cells from mice infected 21 days earlier. This binding was not related to alloantibodies because these were absorbed prior to testing. The demonstration of rickettsial antibody staining of infected cell associated antigen(s) in this assay system provides a new method for the detection of R. tsutsugamushi infection. PMID- 3097833 TI - Detection of humoral immune response to Gnathostoma spinigerum in mice. AB - The humoral immune response to early third stage larvae (EL3) and advanced third stage larvae (AL3) of Gnathostoma spinigerum infection was studied in mice by Ouchterlony gel diffusion technique. The antibodies was detected at week 3 in mice infected with EL3 and remained up to week 10 after infection. Highest positive sample of sera were demonstrated at week 4 to week 7. Similar results were obtained from AL3 infected sera except the antibodies was found and disappeared earlier (week 2 to week 6). G. spinigerum larvae recovery from mice in both groups showed that the number of advanced third stage larvae located in muscle correlated to the peak of positive sera. No cross reaction was observed on positive sera of G. spinigerum and antigens of A. cantonensis, P. siamensis, T. spiralis, O. viverrini and A. ceylanicum. Cross reaction was shown on the G. spinigerum antigen against rat sera with angiostrongyliasis and bandicoot sera with paragonimiasis. PMID- 3097834 TI - Schistosoma japonicum-like infection in Phichit province, northern Thailand: a case report. AB - A case of human schistosomiasis from Phichit Province is presented. Schistosome eggs were found in the ileo-caecal mass of a 44-year old woman, native of Sak Lek, Muang District. Histologic pictures revealed an early acute granulomatous lesion which consisted of predominantly eosinophils without multinucleated giant cells and fibrotic change suggesting a recent infection. On the basis of the shape and microscopic appearance of the eggs, they are smaller than those described previously for Schistosoma japonicum, probably those of S. mekongi, a related species. This is the third histologic-confirmed case of schistosomiasis in this locality. Addendum: At the time of the manuscript preparation, another case of schistosomiasis was diagnosed. A 55-year old man who lives entirely in the very close adjacent village to the present case was admitted to the Ramathibodi Hospital, Bangkok with chronic hepatosplenomegaly in January 1986. Amyloidosis was suspected and rectal biopsy revealed schistosome eggs, some contained miracidia with varying degrees of degeneration, some were empty and/or fragmented shells and were surrounded with fibrotic changes and chronic cellular infiltration (Fig. 5). They were identical to those of Schistosoma japonicum. Several fecal examinations, miracidium hatching and COPT yielded negative results. This finding showed significantly that all schistosomiasis cases reported from this locality, except the second one, were in the old age group of 40 and above. Further epidemiologic investigation is in progress to delineate this locality as a potential endemic area for this infection. PMID- 3097835 TI - Extensive simultaneous multisegment laminectomy for myelopathy due to the ossification of the posterior longitudinal ligament in the cervical region. AB - Extensive simultaneous multisegment laminectomy (ESML) for treatment of ossification of the posterior longitudinal ligament (OPLL) in the cervical region is a technique which cuts the laminae on the median line and on the pedicles with an air drill, and then, the right and left halves of laminae are lifted simultaneously. This technique provides a protection to the spinal cord that swells instantaneously after decompression. A total of 155 cases were followed up for more than 1 year. According to the Japanese Orthopedic Association's evaluation criteria, 127 cases (81.9%) showed some improvement; specifically, 57 cases (36.8%) were rated excellent; 28 (18.1%), good; 42 (27.1%), fair; 11 (7.1%), unchanged; and 17 (11.0%) had poor results. PMID- 3097836 TI - Experimental study on chemonucleolysis. With special reference to the change of intradiscal pressure. AB - The purpose of this study is to investigate mechanical change in the intervertebral disc after chemonucleolysis. Thirteen monkeys were used. After transperitoneal approach to the lumbar spine, 400 units of Discase was injected into each disc. The animals were killed 1 day; 1, 2, 3, 4, 6, and 12 weeks; and 1 year after chymopapain injection. Compression load was applied to the segment composed of a disc and adjacent vertebral bodies. Intradiscal pressure was measured simultaneously. A linear relationship was noticed between compression load and intradiscal pressure. In chymopapain-injected discs, the pre-existing pressure decreased or disappeared, and the increase of pressure for a given load was lower than that of the control. Our biomechanical study suggested that the decrease of intradiscal pressure as a possible mechanism of symptom relief in chemonucleolysis. PMID- 3097837 TI - The human galactosyltransferase gene is on chromosome 9 at band p13. AB - The structural gene for galactosyltransferase (glycoprotein 4-B galactosyltransferase, EC 2.4.1.38) was localized to human chromosome 9 band p13 by chromosome in situ hybridization using a cloned bovine galactosyltransferase cDNA probe. This chromosomal location is at the same position to which galactose 1-phosphate uridyltransferase, an enzyme which provides the nucleotide sugar substrate (UDP-galactose) for galactosyltransferase, has been mapped. PMID- 3097839 TI - Avoidance of jejunostomy. A reliable method of naso-enteral tube placement after oesophageal surgery. AB - Nutritional maintenance after oesophageal surgery and during treatment of oesophageal disease is given high priority. A method of naso-enteral feeding tube placement suitable for these patient groups was evolved and studied prospectively. A standard nasogastric tube is used as a conduit for a guide-wire over which a soft, small-bone naso-enteral tube is threaded into position. Thirty patients underwent placement of such tubes postoperatively or during treatment of oesophageal disease. Placement and feeding was successful in all. Six patients developed controllable diarrhoea. PMID- 3097838 TI - [Long-term comparative studies on gold, D-penicillamine, and NSAIDs for the treatment of early rheumatoid arthritis. 1. Evaluation of one year's treatment]. PMID- 3097840 TI - Assessment of nutritional status in the oncologic patient. AB - The term malnutrition is a continuum that progresses from only a disequilibrium of intake in relation to needs, to gross structural and functional changes. Furthermore, these changes may be mutually exclusive. How then do we define malnutrition? Strictly, malnutrition starts, as we have shown, when the patient fails to eat enough to meet needs and progresses through a series of functional changes that precede any changes in body composition. These functional changes are related to the duration of reduced intake and its severity. Finally, body wasting occurs, and biochemical indices become abnormal. To base the definition of malnutrition on any one of these changes is inappropriate. Thus, a patient's nutritional status should be defined by the following criteria: nutrient intake in relation to needs; associated changes in organ function; associated changes in body composition; and associated changes in biochemistry. Only by recognizing the different facets of malnutrition can we define its various manifestations in relation to our clinical objectives. In attempting to achieve this goal, we have found muscle function tests a most useful and objective investigational tool. PMID- 3097841 TI - Patterns of fuel utilization during parenteral nutrition. AB - Utilization of fuel in clinical conditions has become an important area of interest to the clinician. Injury and sepsis cause predictable changes in the metabolism of fuel, favoring a shift toward the oxidation of fat. Similar considerations apply to the tumor-bearing host. PMID- 3097842 TI - Nutritional support of the cancer patient: delivery systems and formulations. AB - Safe, efficacious nutritional support of cancer patients requires a complete assessment to determine each patient's fluid, protein, energy, and micronutrient requirements. The authors review the growing variety of enteral and parenteral formulas and access routes available to provide an individualized nutrient prescription, emphasizing new techniques, their specific indications, and complications. PMID- 3097843 TI - Psychological aspects of nutrition and cancer. AB - Cancer and the various treatments employed to combat this disease have an impact on food intake that is psychologic in nature. These psychologic consequences include behavioral responses such as learned food aversions, changes in food preferences, and anticipatory nausea and vomiting. In a second cluster of psychologic consequences are the emotional responses of anxiety and depression. A third type of psychologic consequence is perceptual in nature and is most commonly represented by changes in palatability of foods. A fourth psychologic aspect of food intake and cancer includes attitudinal responses, wherein social, religious, cultural, and other values related to food may change as a consequence of the disease. Studies are needed in this area. Approaches to nutritional care that address the psychologic impact of cancer are described. As a means of maintaining adequate nutritional status, artificial feeding routes may create psychologic problems. In general, cancer and its treatment can exert a negative impact on quality of life. Finally, the ethics of feeding are discussed in terms of care giving versus alimentation. PMID- 3097844 TI - Perioperative nutritional support in the cancer patient. AB - Cancer patients in whom elective surgical intervention is planned are frequently malnourished. Moreover, the tumor itself may be responsible for additionally altering metabolism in the host, although the mechanisms by which this occurs are not clear. All preoperative cancer patients should be carefully surveyed for indices of malnutrition. Patients with a history of inadequate oral protein and calorie intake, an unintentional weight loss of greater than 10 pounds, or a serum albumin level of less than 3.5 gm per dl should undergo a thorough nutritional assessment, including anthropometric measurements, 24-hour urinary urea nitrogen and creatinine measurements, and recall skin antigen testing. Surgical risk may be predicted by using indices that are sensitive and specific in assessing preoperative parameters of malnutrition. Adequate nutritional support for 7 to 10 days prior to surgery should be provided to all patients falling into the high-risk category and has been shown to significantly reduce the rate of postoperative complications and death in this group. Generally, a serum albumin of less than 3 gm per dl, a recent unintentional weight loss of greater than 10 to 15 per cent of normal body weight, and/or skin test anergy should be considered to designate high risk. In the formulation of a nutritional plan, estimates of daily energy requirements are essential and can be made by use of the Harris-Benedict equation, metabolic cart measurements, and perhaps 24-hour urinary creatinine values. Generally, 30 to 45 kcal per kg of body weight with 1.2 to 1.5 gm of protein per kg of body weight daily, regardless of the route of delivery, will provide adequate nutritional support. Patients should be fed by the enteral route if possible. Although oral intake is preferable, many malnourished cancer patients will be unable to achieve necessary protein and calorie requirements in this manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3097845 TI - Influence of nutritional status on the resumption of adequate food intake in patients recovering from colorectal cancer operations. AB - The influence of nutritional status on the resumption of adequate food intake in 101 patients recovering from colorectal cancer operation was examined. Two thirds of these patients were well-nourished; the others were malnourished. Malnutrition criteria were serum albumin of less than 3.5 gm per dl plus any two of the following four factors: recent weight loss greater than 10 per cent or weight for height, mid-arm circumference, and triceps skinfold thickness lower than the tenth percentile. Over half of the well-nourished patients were eating 60 per cent or greater of their caloric requirements by the tenth postoperative day, whereas only one quarter of the malnourished patients had attained this intake. the morbidity and mortality in 33 malnourished patients was 52 and 12 per cent, respectively, compared with 31 and 6 per cent (p less than 0.01) in 68 nourished patients. The duration of postoperative functional starvation in malnourished patients without complications increased to an average of 22 days following a complication and was further prolonged after a complication. Age or operative procedure (curative or palliative) did not influence complication rate. Our data suggest that postoperative nutritional support as either TPN or enteral feeding using an elemental diet is indicated in malnourished patients and in well nourished patients immediately following a complication requiring therapeutic intervention. PMID- 3097846 TI - Value of nutritional support in adult cancer patients. AB - Both the presence of cancer and oncologic therapy cause metabolic alterations that may decrease the ability of the host to maintain anabolism. Nutritional support, properly administered, will replenish lean body mass, visceral proteins, and immunocompetence in human beings and experimental animals with small to modest tumor burdens. To date, stimulation of tumor growth by intravenous hyperalimentation in malnourished patients has not been documented scientifically. The exact role of intravenous hyperalimentation, in combination with chemotherapy or radiation therapy, is controversial, whereas the role of nutritional support for the malnourished surgical patient is more firmly established. PMID- 3097847 TI - Nutritional support of children with neoplastic diseases. AB - There are numerous factors promoting the development of PEM in the child with cancer. Some of these factors are related to the tumor, many to the treatment itself, and some to failure of recognition of PEM. Not all children with cancer are at great risk for the development of PEM. These patients must be monitored and supported with comprehensive enteral programs. Children who have developed or are at risk for PEM must be identified and supported with CPN or PPN plus CEN during early intensive periods of treatment and during the later phases of abdominal radiotherapy, operative resection of tumor, or relapse. The decision to institute CPN must be based not only on the child's current nutritional status but also on the nature of the therapy he or she is soon to receive and the likelihood that he or she will be able to maintain an adequate intake during that therapy. Realistic goals must be set for nutritional support. The value of nutritional intervention lies in its ability to correct or prevent the development of adverse effects related to PEM. This support is hoped to contribute to improved tolerance of therapy, increased energy to complete normal day-to-day activities, and an improved sense of well-being for the child. If these goals have been accomplished, then the nutritional therapy has been successful. PMID- 3097848 TI - The allograft response. AB - The allograft response is a response by host T lymphocytes reacting to transplantation antigens that are carried on allogeneic lymphoreticuler cells. In vivo this response usually leads to graft rejection. It is possible to circumvent this response by the elimination of the lymphoreticular cells from the grafts prior to transplantation. The paradox of the strong response to transplantation antigen on lymphoreticular cells and the weak response to the same antigen on graft parenchymal cells can be explained by the signaling requirements for T lymphocyte activation. PMID- 3097849 TI - Diagnosis-related groups and the salvagable trauma patient in the intensive care unit. AB - We reviewed 59 patients with trauma treated in the surgical intensive care unit (SICU) in 1983 comparing hospital charges with payments calculated from diagnosis related groups (DRG). There were 37 male and 22 female patients with a mean age of 38.3 years. The mechanism of injury was blunt trauma in 42 and penetrating injury in 17 patients. The mean injury severity score (ISS) was 30.7 +/- 13.8 (mean plus or minus standard deviation). The duration of SICU care was 5.4 +/- 6.1 days. Over-all, 18 patients died. For the entire group, payment based upon a DRG system would have resulted in an over-all loss of $1,468,094.00 or $24,883.00 dollars per patient. Calculated DRG payments would have accounted for only 32.3 per cent of the total hospital charges. Calculated losses for 41 survivors would have been $1,098,431.00 dollars. Length of stay had a significant relationship to the calculated DRG payment (r = 0.69, p less than 0.001) but account for only 48 per cent of the variance. DRG only accounted for 26 per cent of the variance in charges despite a statistically significant relationship (r = 0.51, p less than 0.001). No statistically significant relationship was found between ISS and hospital charge by linear regression (r = 0.20, p greater than 0.01) or between ISS and DRG payment (r = 0.14, p less than 0.4). DRG as presently formulated would only pay one-third of total hospital charges for patients with trauma requiring SICU care. Present DRG payment schedules reflect neither the elements of care currently expended nor the modifiers necessary to adjust for acuity and severity. The ISS score would not be a useful modifier to correct DRG payment in this high cost group. PMID- 3097850 TI - Anatomic bases of the surgical division of Kent bundles in the posterior septal area of the heart. AB - The first part of this paper deals with the general anatomy of the postero-septal area of the heart, with particular emphasis on the relationships between the mitral and tricuspid anuli and the right fibrous trigone, between the conducting system and the interatrial septum, and between the right atrium and the posterior superior process of the left ventricle. In the second part, we describe the operative procedure that has been developed for dividing right and left posteroseptal Kent bundles. The key to this technique is the opening of the right atrium along the tricuspid anulus down to the orifice of the coronary ostium; this offers an excellent exposure on the posterior aspect of the septal area, and allows dissection of the sulcus fat pad from the muscular portion of the interventricular septum and the adjacent posterior superior process of the left ventricle down to the level of the mitral anulus. This planned dissection increases the likelihood of interrupting the anomalous pathways without injury to the normal conducting system which remains encompassed within the interatrial septum and the right fibrous trigone. PMID- 3097851 TI - The nerve branches to the external anal sphincter: the macroscopic supply and microscopic structure. AB - The study was performed using 45 pelvic half section specimens (41 fetal ones and four adults). The macroscopic dissection followed the nerve branches from their spinal roots up to the external anal sphincter. Three nerve branches were found: the anterior ramus arising from the external perineal nerve, the inferior rectal nerve and an independent posterior branch. The anterior and the inferior rectal nerve branches always emerged from the pudendal plexus. The posterior branch arising either from S4 or from the inferior rectal nerve was only found in (31%) of our cases. Five anatomical distributions are described, percentages of every type notified. The fibre content of these nerve bundle branches was evaluated through histological sections using Heidenhain's azan stain and Luxol fast blue. The branches consisted of 2,896 to 2,137 fibres, 20% of them being unmyelinated and 80% containing various myelinated fibres. The nomenclature of these nerve branches has to be debated. The terms of anterior, middle and posterior anal nerves seem more suitable. PMID- 3097852 TI - Morphologic and functional anatomy of the subclavian veins. AB - 50 jugulo-subclavian venous junctions were removed to study the endovenous structures of the subclavian vein and of this junction. The diameter of the subclavian vein is always less than that of the internal jugular vein. Valvules were constantly found, whereas endovenous structures such as those found in the ilio-caval junctions were very rare. In view of these findings, these structures may be regarded as of embryologic origin. PMID- 3097854 TI - Spleno-gonadal fusion: anatomic and angiographic study of a case. AB - The authors report a case of spleno-gonadal fusion in which the advantage of an angiographic study permitted, for the first time, an analysis of the vascularization of this malformation. The embryologic study explains the malformations associated with the continuous type of spleno-gonadal fusion. PMID- 3097853 TI - Ultrasonographic anatomy and diagnosis of fetal uropathies affecting the upper urinary tract. II. Nonobstructive uropathies. AB - The authors describe the ultrasonographic anatomy and semiology of allowing detection of the main types of fetal non-obstructive uropathies. The results of the author's personal experience in this domain are compared to data from the literature. Differential features of the uropathies are given and the limitations and practical significance of prenatal and postnatal ultrasonography are discussed. PMID- 3097855 TI - An urgent reform: French anatomic terminology. PMID- 3097856 TI - The anatomical basis for retrorenal extensions of pancreatic effusions: the role of the renal fasciae. AB - Retrorenal extension of pancreatic inflammatory processes are considered to involve invasion of the posterior pararenal space. Analysis of computed tomographic (CT) images demonstrates preservation of posterior pararenal fat in most patients, implicating some other mechanism. We have examined the anatomical basis for these retrorenal extensions in static and functional studies of 12 cadavers using CT imaging, dissection and histological techniques. We observed that the posterior renal fascia was thicker than the anterior, that it could be easily separated into two layers by manual dissection and injections of liquid latex, that the inner (anterior) layer of the posterior fascia was continuous with the anterior fascia and the outer layer continuous with the lateroconal fascia. The point at which the two layers of the posterior fascia separated laterally and the medial extent of the posterior fascia varied considerably in CT scans of 100 patients. These data are interpreted to mean that pancreatic effusions extend posterior to the kidney by separating the two layers of the posterior renal fascia. PMID- 3097857 TI - A contribution to the study of the facial artery, its branches and anastomoses; application to the anatomic vascular bases of facial flaps. AB - The authors present the results of dissection of 40 facial arteries and their collaterals. The study of the collaterals is specifically for the cervical portion of this artery and especially for the three segments of its facial portion. The artery and its collaterals are extremely variable as regards its mode of termination. 4 types of artery are presented: labial, angular, nasal and abortive. The global description of the vascularization of the face and the principal anastomoses leads on to a study of the facial flaps and the plastic surgery of the face. PMID- 3097858 TI - [Does radiosterilization of the vagina occur through therapeutic radiation dosages?]. AB - The endogenous genital flora is a major source of infections of the female genital tract, especially in patients with cervical or endometrial cancer. Until recently the "radiosterilisation of the vagina", respectively a prophylactic and/or therapeutic effect of irradiation (external high voltage as well as intracavitary-radium) concerning infections was postulated in the literature. This theory was disproved in a prospective clinical and bacteriological study covering 48 patients with advanced cervical cancer undergoing primary intracavitary radium-irradiation and 38 patients with inoperable endometrical cancer, undergoing primary Iridium-192-afterloading. Following intracavitary radium for cervical cancer some typical nosocomial pathogens like Streptococcus faecalis, Enterobacter, Klebsiella, Proteus and Pseudomonas were isolated significantly more frequently than before treatment. Likewise, the mean number of aerobic bacterial species increased significantly after irradiation. Also primary Ir-192 (afterloading) irradiation did not alter the frequency of isolation of the resident flora in endometrial cancer patients. Therefore, "radiosterilisation" of the vagina as result of radiotherapy does not exist. PMID- 3097859 TI - Simple, accurate, safe, and cost-effective percutaneous transperineal template technique for permanent 125iodine interstitial brachytherapy of prostate cancer. AB - We present the technique, intraoperative and postoperative complications of percutaneous transperineal template permanent 125iodine interstitial brachytherapy of prostate cancer. The percutaneous transperineal template permanent iodine interstitial brachytherapy under "C-arm" fluoroscopic guidance is a simple, easily-learned, accurate and rapid procedure which can be performed without subjecting the patient to celiotomy. We have treated 58 patients by the transperineal percutaneous permanent interstitial brachytherapy. 33 of 58 patients also had a staging celiotomy just prior to the brachytherapy. In the group of 22 patients undergoing brachytherapy without celiotomy and without adjuvant external-beam pelvic radiotherapy, there were no major complications. Blood transfusions were not required by any patients who underwent percutaneous transperineal permanent iodine interstitial brachytherapy without celiotomy. PMID- 3097860 TI - Neural regulation of heterotopic islets of Langerhans. AB - The possibility of vagal reinnervation to intrasplenic islet grafts was examined by measuring portal insulin response to electric stimulation of the dorsal vagus nerve in autografted dogs. Grafted islets responded appropriately to an exogenous cholinergic agent given intravenously. However, no insulin secretory response could be observed in grafted dogs after vagal stimulation, which markedly increased portal insulin levels in control dogs. Therefore, intrasplenic islets are not under direct vagal control. At the basal state, normal oscillatory release of insulin was observed in the animals with grafts, suggesting that the mechanism of rhythmic basal insulin release is intrinsic to the islet of Langerhans with no regulatory input from the vagus nerve or any element of pancreatic structure. PMID- 3097862 TI - [Erythromyelosis in the outcome of partial red cell aplasia]. AB - The authors describe two women with a history of partial red-cell aplasia of the bone marrow without any remissions for 2 and 3 years, followed by the development of erythromyelosis. The latter lasted from 1 to 2 years, the total illness duration being 4 to 5 years. All the attempts to achieve remissions with the use of splenectomy, mono- and polychemotherapy with a purpose of immunosuppression ended in failure. Partial red-cell aplasia is viewed as preleukemia. PMID- 3097861 TI - [Correction of neutropenia with lithium carbonate during the radiation treatment of lymphogranulomatosis patients]. AB - The purpose of the investigation was to study the effect of lithium carbonate on the time-course of changes in neutrophil leukocytes of the peripheral blood. Sixty-nine patients afflicted with Hodgkin's disease were entered into the study. Greater preservation of the content of neutrophil leukocytes was attained with the use of lithium carbonate coupled with radiation therapy. At the same time administration of lithium carbonate in the interval between the stages of anticancer treatment brought about an increase in the neutrophil count. PMID- 3097863 TI - Effect of verapamil and sodium cromoglycate on leukotriene D4 induced bronchoconstriction in patients with asthma. AB - Leukotriene D4 (LTD4) may be an important mediator in asthma. The effect of verapamil and sodium cromoglycate on LTD4 induced bronchoconstriction has been examined in seven patients with asthma. The bronchoconstrictor response to increasing concentrations of inhaled LTD4 (0.0032-50 micrograms/ml) was assessed by measuring changes in FEV1, specific airways conductance, and flow rate at 30% of vital capacity (V30(p)). Results were expressed as the provocation concentration (PC) producing a 10% fall in FEV1 (PC10FEV1), a 35% fall in specific airways conductance (PC35SGaw), and a 30% fall in flow at 30% of vital capacity (PC30 V30(p)). Neither verapamil nor cromoglycate inhibited LTD4 induced bronchoconstriction in asthmatic subjects. These results suggest that in asthmatic patients LTD4 induced bronchoconstriction is not mediated via verapamil or cromoglycate sensitive mechanisms. PMID- 3097864 TI - Conformity of bacterial growth in sputum and contamination free endobronchial samples in patients with cystic fibrosis. AB - The use of sputum cultures to guide the antimicrobial treatment of patients with cystic fibrosis has been questioned. Bacterial growth and antibiotic susceptibility patterns of 33 culture pairs from sputum and contamination free endobronchial swabs from 14 patients with cystic fibrosis were compared. As expected, Pseudomonas aeruginosa of the mucoid and non-mucoid type, Staphylococcus aureus, and Haemophilus influenzae were the organisms most frequently found. Absolute or good agreement was found in 73% of the culture pairs. The accuracy of the sputum cultures improved with the duration of antimicrobial treatment. The extra information gained from the endobronchial culture did not change the antimicrobial strategy from that based on the sputum culture alone. It is concluded that sputum cultures provide accurate information about the bacterial colonisation of the lower respiratory tract in patients with cystic fibrosis and therefore can be trusted both at onset of treatment and during the entire treatment period. PMID- 3097865 TI - Comparative trial of two non-sedative H1 antihistamines, terfenadine and astemizole, for hay fever. PMID- 3097867 TI - Severe factor VIII deficiency in a chromosomally normal female. PMID- 3097866 TI - Rapid diagnosis of sputum negative miliary tuberculosis using the flexible fibreoptic bronchoscope. AB - Acid fast bacilli are seldom identified by direct staining of sputum smears in patients with miliary tuberculosis, so that delays in diagnosis are common. We report 41 patients with miliary tuberculosis who had negative sputum smears and who underwent bronchoscopy, bronchial brushing, and transbronchial biopsy. In two patients the procedure was repeated. A definitive diagnosis was obtained from bronchoscopy in 34 patients (83%). Bronchial brushings yielded Mycobacterium tuberculosis in 24 of 42 bronchoscopies (57%), 13 from direct smear and a further 11 from culture only. Transbronchial biopsies were diagnostic in 30 of 41 procedures (73%), 28 from histological appearances, one from direct smear of the biopsy specimen, and another exclusively from culture. A rapid diagnosis was established in most patients (27/34), either by direct smear of brushings or biopsy specimens only (5), by histological examination only (14), or by both direct smear of brushings and biopsy specimens only (5), by histological examination only (14), or by both direct smear of brushings and histological examination (8). The diagnosis was confirmed later in a further seven patients by culture of brushings or specimens; in five of these non-caseating granulomas were initially found by histological examination. Fibreoptic bronchoscopy is a valuable technique for rapidly establishing the diagnosis of miliary tuberculosis. PMID- 3097868 TI - Inhibition of the effects of thrombin on guinea pig platelets by the diacylglycerol lipase inhibitor RHC 80267. AB - Phospholipase C (PLC) and diacylglycerol lipase (DGL) activities were found in guinea pig platelet microsome preparations. No phospholipase A2 (PLA2) activity was detected. RHC 80267 (1,6-di (0-(carbamoyl) cyclohexanone oxime)hexane) inhibited DGL activity (IC50 = 4 uM) from guinea pig platelet microsomes but had no effect on PLC. RHC 80267 inhibited platelet aggregation (IC50 = 11 uM), release of arachidonic acid (AA), its metabolites, and ATP (IC50 = 4.5 uM) when guinea pig platelets were challenged with a low concentration of thrombin. We propose that PLC-DGL is an important enzymatic pathway for the release of AA in guinea pig platelets. PMID- 3097869 TI - Fibronectin decreases pulmonary vascular permeability under baseline conditions and after administration of arachidonic acid in rabbit lungs. AB - In blood- and plasma-free perfused isolated rabbit lungs, the influence of albumin and soluble fibronectin on vascular permeability was investigated. The lungs were perfused with Krebs Henseleit buffer containing no protein (KHB), containing 1 g/100 ml bovine albumin (KHAB) or containing albumin together with 100 micrograms/ml soluble fibronectin. The absence or presence of albumin had no influence on the perfusion pressure, the vascular compliance and the capillary filtration coefficient (CFC), determined by zero time extrapolation of the slope of weight gain which was induced by a sudden venous pressure elevation. Fibronectin caused a slight increase in pulmonary artery pressure, a slight decrease in vascular compliance and an approximately 50% reduction of CFC. In a second set of experiments, KHAB-perfused lungs were stimulated by the administration of 100 microM arachidonic acid (AA) during the second hydrostatic challenge within a sequence of three venous pressure elevations. In the presence of indomethacin, which blocks any significant increase in pulmonary vascular pressure after AA application, this procedure caused an immediate gain in lung weight due to increased pulmonary vascular permeability, with greater than 10 fold increased CFC values subsequent to the AA application. In the presence of 100 micrograms/ml fibronectin, this AA-induced increase in CFC was mitigated to less than 20% of the controls without the glycoprotein, with correspondingly severalfold reduced lung weight gain. In conclusion, the present study provides evidence for a direct influence of circulating soluble fibronectin on lung microvascular integrity and fluid balance under baseline conditions and after stimulation of the pulmonary AA cascade. PMID- 3097870 TI - The inactivation of one- and two-chain forms of tissue plasminogen activator by a series of peptidyl chloromethyl ketones. AB - The inhibition of one- and two-chain forms of tissue-type plasminogen activator by a series of peptide derivatives of arginine chloromethyl ketone was studied. Both forms of the enzyme were inhibited by such reagents at varying rates, dependent on the peptide sequence of the inhibitor. The order of relative effectiveness of the inhibitors was the same for both one- and two-chain tissue plasminogen activator. However, an approximately ten to twenty-fold higher concentration of reagent was required with the one-chain activator to produce similar rates of inactivation. It appears that the specificity of the active sites of the one and two chain forms of tissue plasminogen activator are very similar. It is suggested that the differences in enzymatic properties of the two forms are due mainly to effects on binding (Ki) rather than on the rate of alkylation and inhibition (k2). PMID- 3097872 TI - A comparative study of the efficacy and specificity of tissue plasminogen activator and pro-urokinase: demonstration of synergism and of different thresholds of non-selectivity. AB - Clot lysis and non-specific plasminogen activation in human plasma by tissue tissue plasminogen activator (t-PA) and/or pro-urokinase (pro-UK) were studied. The fibrinolytic activity of pro-UK was expressed as latent units, i.e. measured after activation with plasmin on a fibrin plate against the reference standard. The t-PA unitage was assigned on a weight basis of a similar equivalence of 100,000 IU/mg. To simplify comparison, both activators were expressed in IU (1 IU = approximately 10 ng). At low concentration (1-50 IU/ml), t-PA induced more effective and more linear clot lysis, whereas pro-UK induced lysis was preceded by a lag phase. The two activators were equivalently effective at higher concentrations and saturated at the same lysis rate. Clots made from platelet rich plasma or whole blood were more responsive to lysis by pro-UK but not t-PA than corresponding platelet poor clots. At very low concentrations (2.5-5 IU/ml) of t-PA combined with moderate concentrations (25-50 IU/ml) of pro-UK, a synergistic effect on clot lysis, which was fibrin-specific, was observed. Plasminogen and fibrinogen and the appearance of plasmin-inhibitor complexes in plasma were measured after incubation with either activator with and without a clot present. Non-specific plasminogen activation occurred above a certain concentration of either activator but was found at lower concentrations of t-PA than pro-UK. In the absence of a clot, plasmin generation occurred with t-PA at about 30% of the concentration at which pro-UK induced a corresponding effect. It is concluded that there are important differences in the fibrinolytic and clot selective properties of t-PA and pro-UK, and that some of these properties may be complementary resulting in a fibrin specific, synergistic fibrinolytic effect. PMID- 3097871 TI - Membrane fluidity and thromboxane synthesis in platelets from patients with severe atherosclerosis. AB - Platelets play an important role in the development of atherosclerosis. The arachidonic acid, whose oxygenated metabolites are potent regulators of the platelet-vessel wall interactions, is released from membrane phospholipids by the phospholipase (s) system (s). These membrane-linked phenomena are strongly modulated by the membrane physical properties. The present study was carried out to investigate the relationship between membrane fluidity and arachidonic acid metabolism in platelets from atherosclerotic patients. Twenty-one patients with peripheral vascular disease and twelve controls were studied. Platelets from patients showed an increase in membrane fluidity and enhanced thrombin-stimulated thromboxane synthesis. No alterations were found, however, in total phospholipid fatty acid composition. A significant decrease in the cholesterol/phospholipid ratio could account for the alterations in the membrane physical properties described in the platelets from patients. PMID- 3097873 TI - [Insulin and insulin treatment]. PMID- 3097874 TI - Mercuric chloride-, gold sodium thiomalate-, and D-penicillamine-induced antinuclear antibodies in mice. AB - Inducibility of antinuclear antibodies (ANA) by mercuric chloride (HgCl2) was studied in various strains of mice. High response to the treatment was observed in strains A.SW (H-2s), A.CA (H-2f), A.TH (H-2t2), B10.S (H-2s), DBA/1J (H-2q), and P/J (H-2p); strains A.BY (H-2b), B10.M (H-2f), and C3H/HeSnJ (H-2k) showed a low response, while strains A/WySn (H-2a), A/J (H-2a), A.TL (H-2tl), BALB/cJ (H 2d), C57BL/10SnJ (H-2b), B10.A (H-2a), and PL/J (H-2u) did not produce any detectable ANA. Thus, the H-2a haplotype determines resistance to the treatment regardless of the genetic background; the H-2s determines susceptibility, while the H-2b and H-2f are intermediate haplotypes whose effect depends on the interaction with the background genes. Our results with intra-H-2 recombinant strains indicate that the I region of the H-2 complex is the major genetic factor controlling this response. The function of the I region is to control cellular cooperation in the immune response that finally results in production of antibodies specific for a particular antigen. Therefore, we postulated that the I region controls the antibody response to a nuclear antigen released as a result of HgCl2 toxicity in mice. A genetic study of an A.SW X C57BL/10 cross confirmed this observation, showing that resistance to ANA induction by HgCl2 in this strain combination is determined by interaction of a semidominant H-2-linked gene and one or more unlinked genes. The two drugs tested, gold sodium thiomalate and D-penicillamine, also induced ANA in A.SW mice, while other strains tested resisted this treatment. PMID- 3097875 TI - Induced aflatoxicosis in rabbits: blood coagulation defects. AB - The effect of acute and subchronic experimental aflatoxicosis on blood clotting activity and platelets was evaluated. Male New Zealand White rabbits (weighing 2.4-3.2 kg each) were used. In Experiment 1, 19 rabbits were given orally 0.05 mg of aflatoxin B1 (AFB1)/kg of body weight daily from Day 0 through Day 23. Blood samples were collected before dosing and on Days 2, 5, 9, 12, 16, 19, and 23 of the experimental period. In Experiment 2, 40 rabbits were given a single dose of 0.4 mg of AFB1/kg of body weight. Blood samples were collected before dosing and at 12, 24, 36, and 48 hr after dosing. When compared to baseline and control animal values, one-stage prothrombin times and activated partial thromboplastin times of aflatoxin-dosed rabbits were lengthened, and there was a statistically significant decrease in fibrinogen, Factor IX, VIII, and V activities. Platelet counts were significantly increased in subacutely exposed rabbits, and platelet size was decreased in single high-dose treated groups. Factor deficiencies were attributed to a combination of decreased factor synthesis from hepatic insufficiency and consumptive coagulopathy or primary fibrinolysis. PMID- 3097877 TI - Changes in liver polyamines due to aflatoxin B1. AB - Changes in liver polyamines of rats and mice of both sexes injected with aflatoxin B1 (AFB1) were determined. AFB1 significantly enhanced liver polyamines of both susceptible and resistant animals, viz. rats and mice, respectively. Sex appears to have little influence on AFB1-mediated stimulation of liver polyamine levels. AFB1 significantly reduced liver polyamine in growing rats reflecting the inhibitory effect of this carcinogen on induced polyamine synthesis. PMID- 3097876 TI - Effects of low subchronic doses of methoxychlor on the rat hypothalamic-pituitary reproductive axis. AB - The pesticide methoxychlor (MXC) is known to possess a weak estrogenic action and has been found to have a number of toxic effects on the rodent reproductive system, primarily at the gonadal level. The purpose of this study was to explore the influence of MXC on the pituitary and hypothalamic components of the male reproductive system at dose levels that were without detectable testicular effects. At 21 days, male Long-Evans rats were gavaged daily with 25 or 50 mg/kg MXC in corn oil. Controls received vehicle only. After 8 weeks of dosing, no significant changes were seen in serum LH, FSH, or prolactin, nor in the pituitary concentrations of LH or FSH. Pituitary prolactin was elevated for both doses, and pituitary fragments perifused in vitro released more prolactin than did controls. The concentration of gonadotropin-releasing hormone (GnRH) was higher in the mediobasal hypothalamus, but only for the 50-mg/kg group. At this dose, there was a corresponding increase in the KCl-stimulated release of GnRH. The data suggest that previously reported reproductive effects of MXC may be mediated, at least in part, through an elevation in prolactin concentration and release, which in turn is able to influence hypothalamic levels of GnRH. This prolactinemic effect may well represent an early component of the adverse action of MXC on the reproductive system. PMID- 3097878 TI - Embryotoxicity and teratogenicity of lithium carbonate in Wistar rat. AB - Lithium carbonate was administered orally to pregnant Wistar rats from day 6-15 of gestation at doses of 50 and 100 mg/kg. Evidence of embryotoxic and teratogenic potential of lithium carbonate was noticed at the dose of 100 mg/kg. Reduction in number and weight of the litter, increase in the number of resorptions, wavy ribs, short and deformed bones of the limbs, or an increased incidence of incomplete ossification of sternebrae and wide bone separation in the skull were the important findings suggesting the nature and extent of embryotoxicity and teratogenicity of lithium carbonate in Wistar rats. PMID- 3097879 TI - Scanning electron microscopy of heart muscle freeze-dried from dimethylsulfoxide for simultaneous demonstration of cell morphology and microvascular function. AB - Scanning electron microscopy was used to examine cryofracture surfaces of ventricular myocardium from glutaraldehyde fixed rat and rabbit hearts subjected to intravascular injection of polymerizing acrylic resin. This allowed simultaneous observation of morphological features of cardiac muscle cells and the functional state of their associated small blood vessels. Because the resin injected to identify capillaries accessible to flow might be soluble in commonly used tissue dehydrating agents, alternative preparation methods using the cryoprotectants dimethylsulfoxide (DMSO) and glycerol were investigated. Provided a high performance backscattered electron detector and simple environmental cell were used to abolish specimen charging and circumvent potential instrument contamination, immersion in 2.82 M DMSO for 12 hr prior to cryofracture and freeze-drying gave the best results. The SEM appearance of specimens dehydrated in this way differed little from that of specimens prepared by ethanol dehydration and freeze-drying or by acetone dehydration and critical-point drying. Tissue shrinkage was 26.5 +/- 9.4%, comparable to that found after standard methods using solvent dehydration and critical-point drying. PMID- 3097880 TI - A rapid method for detection of tyrosinase activity in electrophoresis. AB - This rapid and sensitive method for localizing tyrosinase in polyacrylamide slab gels is based on the condensation of Bestthorn's hydrazone (3 methyl-2 benzothiazolinone hydrazone hydrochloride) with the quinone obtained by enzymatic oxidation of phenol. Both monophenolase and diphenolase activities are localized by this method. PMID- 3097881 TI - Immunofluorescent staining of leptospires in pepsin treated histologic sections. AB - A standard immunofluorescent method was modified for the staining of leptospires in formalin fixed, paraffin embedded tissues. Routine histologic sections were deparaffinized and treated with pepsin prior to staining. Pepsin treatment greatly enhanced subsequent staining of leptospires in naturally infected bovine and porcine tissues as well as in artificially infected tissues. Leptospires in naturally infected bovine tissues were usually undetectable in untreated sections but clearly visible in stained pepsin-treated sections. Naturally infected porcine kidney usually contained high levels of leptospiral antigen which could be stained without prior pepsin treatment. However, pepsin treatment of porcine tissues greatly increased the amount of leptospiral antigen detectable and made individual leptospires more conspicuous. The staining method could employ a single antiserum for the staining of leptospires from 13 serogroups. Also, leptospires could be stained in tissues stored in formalin for more than 14 months and in 26-year-old paraffin embedded tissues. PMID- 3097882 TI - [Perfect and load-resistant adapted composite resins for the lateral teeth--a new filling technic]. PMID- 3097883 TI - [Nitrous oxide analgesia in dental practice. Introduction to light nitrous oxide sedation]. PMID- 3097884 TI - [Endosseous oral implantology. Present and future]. PMID- 3097885 TI - Ocular ossification. A case report and review of the literature. AB - The right eye of a 15-year-old boy was removed and found to contain grossly disorganised intraocular tissues, with bone formation. The literature relating to this finding is reviewed. Trauma of an unspecified and undisclosed nature is proposed as the most probable cause. The mechanism by which such trauma might lead to the formation of bone is discussed. PMID- 3097886 TI - Small intestinal permeability in normal Sudanese subjects: evidence of tropical enteropathy. AB - Small intestinal permeability to mannitol and lactulose was studied in healthy English and apparently healthy Sudanese subjects to determine whether any differences were apparent. Permeability was assessed by measuring urinary recovery of the test substances after oral ingestion. The mean excretion of lactulose was significantly higher and the mean excretion of mannitol was significantly lower in the Sudanese than in the English subjects. Lactulose to mannitol excretion ratios were significantly higher in the Sudanese. These data demonstrate abnormal intestinal permeability in the Sudanese subjects and indicate the presence of an asymptomatic enteropathy. PMID- 3097887 TI - alpha-Difluoromethylornithine induces protective immunity in mice inoculated with Plasmodium berghei sporozoites. AB - Mice inoculated weekly with Plasmodium berghei sporozoites while under treatment with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, developed protective immunity against subsequent challenge with this parasite. The percentage of mice protected was similar whether DFMO alone (55%) or DFMO + chloroquine (65%) was used. With chloroquine alone, only 12% of mice were protected. This protection was long-lasting (at least six months). The immunity protected against sporozoites but not against erythrocytic form inoculation. It is suggested that this protection is induced by antigens released from exoerythrocytic schizonts whose further development is inhibited by DFMO. PMID- 3097888 TI - The recognition of Schistosoma mansoni surface antigens by antibodies from patients infected with S. mansoni and S. haematobium. AB - Polypeptide surface antigens of Schistosoma mansoni recognized by schistosomiasis patients have been identified and their strain and species specificity investigated. Antibodies from individuals infected with S. mansoni were used in immunoprecipitation assays of 125I-labelled schistosomulum surface antigens. All individuals surveyed from St. Lucia strongly precipitated antigens of approximately Mr 38,000 to 32,000 and 20,000. These antigens were shown by two dimensional gel electrophoresis to be the same as those recognized by experimentally immunized mice. Although individuals showed a highly heterogeneous response against total polypeptide antigens synthesized in vitro by cell-free translation of adult S. mansoni mRNA, all individuals recognized the same surface antigens. Immunoprecipitation with sera from patients infected with S. mansoni in many different parts of Africa resulted in generally the same antigens being precipitated, although a very high molecular weight antigen(s), not strongly recognized by the St. Lucian sera was also precipitated by most of the African patient sera. One serum from Ghana precipitated the high molecular weight antigen but not the low molecular weight antigens, raising the possibility of the existence of S. mansoni strain(s) exhibiting some diversity in surface antigens. The surface of S. mansoni schistosomula was found to bind strongly antibodies from individuals infected with S. haematobium, demonstrating that most surface antigens are cross-reactive. Immunoprecipitation demonstrated, however, that of the polypeptide surface antigens only the very high molecular weight antigen was recognized by anti-S. haematobium antibodies and that the 38,000 to 32,000 and 20,000 Mr antigens were species-specific. Immunoprecipitation of the polypeptide antigens derived from purified adult surface membranes demonstrated recognition of the same 32,000, 25,000 and 20,000 Mr antigens recognized by chronically infected mice. Again these antigens were found to be species-specific. PMID- 3097889 TI - Immune precipitation and immunoblotting for the detection of Trypanosoma cruzi antigens. AB - The efficiency of immunoprecipitation and immunoblotting for detecting Trypanosoma cruzi antigens using rabbit and mouse antisera has been examined. Comparison of the starting material for each technique showed that the extraction methods resulted in a similar range of polypeptides when assessed by apparent Mr. Reaction with either hyperimmune rabbit sera or a sequential series of sera from infected mice, showed a significant disparity in the range of antigens revealed by each technique. Epitopes on polypeptides greater than 50 kDa were poorly preserved by immunoblotting compared to immunoprecipitation; however, below this threshold both techniques were equally efficient. Under the conditions of assay, it is probable that immunoprecipitation allows effective detection of both sequence and conformational determinants, whereas immunoblotting favours the detection of sequence determinants alone. PMID- 3097890 TI - Bloody diarrhoea after praziquantel therapy. PMID- 3097891 TI - Opportunistic strongyloidiasis in renal transplant recipients. AB - Eight patients with severe strongyloidiasis complicating renal transplantation are reported. Twenty-one additional cases from the English-language literature are reviewed. In this setting, systemic strongyloidiasis is an often baffling illness involving multiple organ systems that is frequently complicated by serious bacterial infection. Bacteremia, meningitis, urinary tract infection, and pneumonia resulting from enteric organisms are common. In order to make the diagnosis, larvae must be sought by direct microscopy of stool, upper intestinal fluid, sputum, urine, or biopsy specimens. Treatment with oral thiabendazole in prolonged or repeated courses is recommended. Effective parenteral therapy is not available. Following treatment, previously parasitized patients must be tested at regular intervals to detect therapeutic failure or reinfection. Screening of patients awaiting renal transplantation for chronic intestinal strongyloidiasis is suggested. Improvement of the observed 52% mortality will depend upon heightened awareness by physicians caring for renal transplant candidates, and upon improved therapeutic regimens. PMID- 3097892 TI - Cryopreservation of mouse pancreatic islets. Effects of fast cooling on islet B cell function and on the outcome of islet transplantation. AB - In most previous studies of cryopreserved isolated pancreatic islets, a slow cooling rate has been employed. We recently observed that faster cooling (5 degrees C/min) resulted in better functional islet preservation than cooling at 0.5 degrees C/min. We found that a culture period after the collagenase isolation of the islets, but prior to freezing, is crucial for the preservation of the islet B cell function. In the present investigation the function of isolated mouse pancreatic islets cooled in Hanks' solution supplemented with 2 M dimethylsulphoxide was compared with that of nonfrozen, cultured islets prepared from the same donors. The islets were cultured in RPMI 1640 + 10% calf serum for 3 days before freezing, and for 3 days after rapid thawing at 37 degrees C. Islets were cooled at rates of 5, 15, or 25 degrees C/min to 70 degrees C and then plunged into liquid nitrogen. All three groups of cryopreserved islets responded with insulin secretion when challenged with high glucose concentrations in batch-type incubations. In further experiments it was found that glucose stimulated (pro)insulin biosynthesis in islets frozen at 25 degrees C/min was the same as that in the controls. Similar observations were made with respect to glucose-stimulated insulin release in perifusion experiments. However, a 30% reduction in insulin content was observed in the rapidly frozen islets. There was no difference in the replicatory capacity of the islets cells in vitro, as determined by an autoradiographic technique, between control islets and islets cooled at 5 degrees C or 25 degrees C/min. Intrasplenic implantation of 600-800 cryopreserved syngeneic islets into alloxan-diabetic mice led to complete or partial normalization of the hyperglycemia in seven of nine mice. When splenectomy was performed in five animals the serum glucose concentrations increased promptly. We conclude that relatively rapid cooling rates may be useful for cryopreservation of isolated pancreatic islets. PMID- 3097893 TI - Comparison of the immunosuppressive effects of cyclosporine, lipid-soluble anesthetics, and calmodulin antagonists. Response to exogenous interleukin 2. AB - The purpose of these investigations was to compare the immunosuppressive mechanism of cyclosporine (CsA) with those of lipid-soluble local anesthetics and calmodulin antagonists. Chlorpromazine (CPZ) and pentobarbital (PB) both inhibit lymphocyte activation by attenuating sodium and potassium ion potentials. CPZ and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) can also block calcium dependent activation processes by inhibition of calmodulin and protein kinase C. All four compounds were found to suppress human and murine lymphoproliferation to both alloantigen or mitogen in a dose-dependent and saturable manner. Exogenous interleukin-2 (IL-2) restored mitogenic responsiveness to cultures suppressed using W-7 and CsA, but not to lymphocytes suppressed with either CPZ or PB. Cytofluorographic analysis revealed that the degree of suppression in drug treated lymphocytes was significantly correlated with the surface expression of receptors for transferrin and interleukin-2. Inhibition of IL-2 activation by PB was demonstrated to result from a blockade of the mitogenic growth factor signal using the IL-2-dependent cell line HT-2. Thus, the mechanism of action of cyclosporine can be differentiated from those of anesthetic immunosuppressants at the level of responsiveness to interleukin-2. The data support the hypothesis that cyclosporine may be an antagonist of calmodulin that selectively blocks early events in T lymphocyte activation leading to IL-2 synthesis, but does not inhibit the expression or function of the IL-2 receptor. PMID- 3097894 TI - International symposium on complications of diabetes--current status of prevention and treatment. The Hague, The Netherlands, March 2-5, 1986. PMID- 3097895 TI - Pharmacokinetics of cyclosporine in toxicological studies. AB - Pharmacokinetic studies performed in toxicological studies indicate that CsA is well absorbed in rats and dogs with absolute bioavailability in the range of 10% to 30% when administered by gavage (olive oil). Exceptions are the guinea pig, the rabbit and marmoset with low bioavailability (less than 5%). CsA is also absorbed in rats when given mixed in the feed. Vehicles may have marked effects on the absolute bioavailability. The correlation between areas under the plasma concentration time curves (AUC) and dose levels is linear in most species up to a dose of 50 mg/kg/d. CsA steady state plasma levels are generally 2 to 3 times higher than after single administration. Measures to reduce CsA nephrotoxicity must consider possible changes of oral bioavailability and immunosuppressive activity as shown for dmPGE2. Drug interactions may be predicted in animal experiments. PMID- 3097896 TI - [Cytochemical and electron microscopic research on the peripheral blood leukocytes and skin fibroblasts in mucopolysaccharidoses]. AB - Cytochemical studies of the peripheral blood leucocytes in patients suffering from mucopolysaccharidoses (MPS) have revealed metachromatic granules in the cell cytoplasm. Electron microscopy of these cells has shown multiple cytoplasmic vacuoles. It is supposed that metachromatic granules in blood leucocytes of patients with MPS observed in the photo-optical studies correspond to the vacuoles found under electron microscope. The obtained data have shown that peripheral blood leucocytes and skin fibroblasts have the common ultrastructure in MPS patients. The data of electron histochemical studies testify to that the vacuoles of skin fibroblasts are filled with glycosaminoglycans. PMID- 3097897 TI - [Genetic frequencies of the ABO and rhesus blood groups in the Tunisian population]. PMID- 3097898 TI - [Conization of the cervix with a CO2 laser]. PMID- 3097899 TI - [The medullary compression syndrome caused by bacterial spondylitis]. PMID- 3097901 TI - Histopathology of BCG and thiotepa treated bladders. AB - In an effort to characterize the pathophysiological differences between the modes of action of BCG and thiotepa in the treatment of superficial bladder cancer, normal female rats received weekly intravesical instillations of both agents. The animals were sacrificed and their bladders were examined pathologically to determine if there were histological differences between the cellular infiltrates found in the BCG and thiotepa treated bladders. Mononuclear cells, particularly T cells, predominated in the BCG treated bladders whereas polymorphonucleated cells predominated in the thiotepa treated bladders suggesting that there may be an immune aspect to the former therapy. The presence of T-cells following BCG therapy suggest a T-cell mediated immune response. PMID- 3097900 TI - Verapamil enhanced in vitro chemosensitivity of a murine bladder carcinoma, FCB. AB - The in vitro enhancement of chemotherapeutic efficacy by verapamil, a calcium antagonist, was assessed using FCB, a transplantable murine transitional cell carcinoma. Exponentially growing FCB cells were partially resistant to treatment with both thiotepa (10(-4) M) and Adriamycin (10(-5) M), however, there was a significant reduction in cell growth when either agent was administered in combination with verapamil (10(-5) M); the effect was evident over a wide range of drug concentrations (10(-4) - 10(-9) M). There was also a pronounced inhibition of DNA precursor incorporation when verapamil was used in combination with either agent. Fluorometric analysis of Adriamycin uptake indicated that verapamil caused an increase in the intracellular concentration of the agent. The data presented are consistent with the postulate that verapamil enhances chemotherapeutic efficacy by altering cellular permeability to the cytotoxic agents. Our study indicates that the use of verapamil in combination with cytotoxic agents for intravesical chemotherapy of bladder tumors may prove to be beneficial in human patients. PMID- 3097902 TI - Effect of renacidin on suture material. AB - Renacidin solution is used sometimes to irrigate renal units with retained calculi after definitive stone surgery. The effects of this solution on the integrity of suture material utilized to close kidneys have not been determined previously. In an attempt to define the best suture material to use when postoperative renacidin irrigation is contemplated, we studied the effects of this solution on a variety of sutures commonly used in genitourinary surgery. PMID- 3097903 TI - Phase I trial of alpha-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG) in patients with advanced prostatic cancer. AB - Both alpha-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG) inhibit sequential enzymatic reactions in the pathway of polyamine biosynthesis. Since polyamines may be important factors in proliferation of cancer cells and DFMO combined with MGBG has shown synergistic cytotoxicity in an experimental prostatic tumor, we evaluated these agents in phase I clinical trial involving 5 patients with advanced, hormone-resistant prostatic cancer. Toxic reaction to combined DFMO and MGBG was dose-related and included nausea, fatigue, and diarrhea especially with the higher doses of MGBG. No therapeutic responses of significance were seen, but toxicity precluded adequate evaluation. Future Phase II studies of combined DFMO and MGBG should employ low, nontoxic doses of MGBG combined with evaluation of polyamine levels and inhibition of polyamine enzymatic activity to minimize toxicity. PMID- 3097904 TI - Ultrastructural microbiology of infected urinary stone. AB - Scanning and transmission electron microscopy of an antibiotic-treated infected urinary stone demonstrates a thick bacterial biofilm adhering to the surface of the stone. Cultures of the crushed calculi indicated the viability of the bacteria. Exopolysaccharide secreted by the bacteria develops a matrix or glycocalyx that appears to protect the biofilm-forming sessile bacteria from antibiotics. PMID- 3097905 TI - [Use of the CO2 laser and an accessory instrument in surgery of the major duodenal papilla]. PMID- 3097906 TI - Nature and classification of viruses affecting small animals. AB - The classification of animal viruses is predicated upon the various parameters discussed herein and the molecular biology of viruses. Although many of the parameters used for classification purposes have little obvious relation to the disease the veterinarian observes, it is necessary to utilize this information collectively to understand viral classification and its relationship to disease pathogenesis, treatment, diagnosis, and prevention because all these are predicted on the classification of animal viruses (Table 2). PMID- 3097907 TI - Persistent viral infection. The carrier state. AB - A persistent viral infection is one in which the virus in a replicating or non replicating form persists in the host beyond the normal recovery and elimination period for that particular viral infection. The clinical significance and mechanisms of persistence, when known, are discussed for the important viral infections of dogs and cats. Particular emphasis is given to feline viral rhinotracheitis, feline calicivirus, canine distemper, and feline leukemia. PMID- 3097908 TI - [Similarity in the incidence of mastitis in the daughters of related bulls]. AB - The overall prevalence of mastitis in the cow population, selected with respect to sire relatedness, was 12%. As positive for mastitis the cows with positive bacteriological findings in milk were considered. In order to objectify the evaluation by regarding the lactation number achieved, the index of morbidity In was introduced (In = number of positive findings/lactation achieved). Using this index, the groups of halfsisters--daughters of bulls and their sons--were compared and within-group variances were calculated. Differences in In between the groups of unrelated bulls were highly significant (P less than 0.01). In the progeny of sons of the same bull no significant differences were found. This indicates the role of genotype in the susceptibility to mastitis. Mean In value was 0.04 and 0.05 for the progeny of Czech Pied and Friesian breed, resp. No marked differences were observed between the groups of daughters of related bulls. The portion of Staphylococcus infections in the total number of positive findings was higher in the progeny of Friesian bulls (26.3 and 19.8% for the first and the second generation, resp.) than in the progeny of Czech Pied bulls (16.2 and 16.5% for the first and the second generation, resp.). PMID- 3097909 TI - [Genetic markers in the blood and their relation to metabolic parameters in dairy cows]. AB - A relationship between the genetic markers of blood (blood groups, serum polymorphic proteins) and the clinico-chemical parameters was studied in the dairy cows of the Slovak Pied breed. Antigens belonging to systems A, B, C, F, S, R, T, Z and the polymorphic traits genetically controlled from loci Tf, Cp, Am and Hb were identified in all the animals subjected to testing. The values of the parameters of acid-base balance and concentration of 13 metabolic components were repeatedly determined in the experimental period. The results of the F-test indicated that there were no significant differences in the values of any of the tested parameters between the phenotypes of the A, J, Am, Tf and Cp systems. Of the 21 parameters tested, statistically significant differences were found in 11 parameters between some alleles of the C, FV, T, Z and Hb systems. PMID- 3097910 TI - [Urinary delta-aminolevulinic acid levels in dairy cows during lead loading from feed rations under normal conditions of rearing in the Western Slovakia Region]. AB - The concentration of delta-amino levulinic acid (ALA) was determined in the urine of clinically healthy cows of 14 herds in the West-Slovakian region. The content of lead was determined at the same time in the components of feed rations. The ALA concentration values were converted to values per uniform specific weight of urine and per gram of secreted creatinine to match literary sources where the ALA concentration is given in these two quantities. The approximate intake of lead by the animal bodies in milligrams per head/day and per kg of live weight was calculated from lead content in feed rations. The average ALA concentration in the urine of dairy cows was 42.7 +/- 20.2 mu mol per 1 of urine (36.8 +/- 18.7 mu mol per g of creatinine), the average lead intake from feed being 0.157 mg per kg of live weight. The ALA concentrations in urine refer to animals given normal feeds with no lead contamination and as such can be considered as physiological values. Statistically significant correlations were recorded between ALA concentrations per litre of urine at the uniform specific weight of 1030 g per litre and the values converted per gram of secreted creatinine (r = 0.789). The upper biological tolerance limit of ALA concentration in urine (105.0 mu mol per litre) was determined by mathematico-statistical methods. Values above this limit could be indicative of an increased lead stress of the cows' bodies. PMID- 3097911 TI - [Biochemical, hematologic, immunologic and cytogenetic study of papillary dermatitis in fattened pigs]. AB - Examinations were performed of 31 fattened pigs suffering from papular dermatitis (PD) and 33 fattened pigs without dermal changes (C) coming from the D. large pig fattening farm and the production breeding herd of pigs. The weight of the pigs was from 95 to 105 kg. Both farms are sited in a mining area (intensive lignite extraction). The PD pigs, compared with the controls (C), had less total protein, cholesterol and calcium in their blood serum and increased concentrations of thyroxine (T4), non-esterified fatty acids (NEFA), vitamins A and E, inorganic phosphorus and potassium, and the higher alanine aminotransferase (ALT) activity. The PD pigs also had an increased leucocyte count in blood. In their peripheral lymphocytes the PD pigs had a significantly higher number of aberrant cells, 3.9 times higher number of chromosome breaks, slightly increased rate of sister chromatid exchanges, but half the number of chromosome exchanges of the C pigs. No differences between PD pigs and the controls were recorded in the response of the T-lymphocytes of peripheral blood to non-specific phytohaemagglutinin stimulation; neither were there any substantial differences in the concentration of serum immunoglobulins of the IgG, IgM and IgA classes. The PD and C pigs of both herds (the D. and M. farms) had low concentrations of all three serum immunoglobulins. The higher occurrence of PD in the D. herd, compared with the M. farm, is associated with a greater reduction of serum immunoglobulins (IgM by 38%, IgA by 25%, IgG by 15%). PMID- 3097912 TI - [Estradiol-17beta in the blood of boars with disorders of sexual potency]. AB - The levels of oestradiol-17 beta (E2) in the blood plasma were evaluated in 15 boars exhibiting signs of sexual potency disorders and in 20 boars with no such disorders before and after i. v. administration of chorion gonadotropin (HCG). No significant difference (P greater than 0.05) was found in the E2 levels in the blood plasma of the boars of the two groups before HCG administration. Two hours after the i. v. injection of 500 I. U. of HCG, an insignificant increase in the basal levels of E2 was recorded, reaching on the average 28.9% in the boars with potency disorders and 38.8% in those with no potency changes. Neither were there any significant differences in the E2 levels determined after HCG treatment between the boars with and without sexual potency disorders. It is inferred from the results that deviations in E2 concentration in the blood obviously do not contribute significantly to disorders in the sexual potency of boars. PMID- 3097913 TI - [Microscopic fungi in chicken feed mixtures, their toxigenicity and toxicity for the chick embryo]. AB - Contamination with microscopic fungi was studied in broiler complete feed mixtures in 1983-1984. The contamination levels ranged from 10(1) to 10(5) of fungus units per gram of feed (mostly around 10(3) units per gram). Sixty species of microscopic fungi of sixteen genera were isolated from the feeds. The genera Aspergillus and Penicillium occurred most frequently (97% of samples), followed by Mucor (93%), Cladosporium (79%), Rhizopus (52%) and Fusarium (41%). Of the 64 isolates of ten species of microscopic fungi, 42 (66%) were toxicogenic, and out of 49 such strains, 27 (55%) were toxic. PMID- 3097914 TI - [Testing the protective effectiveness of vaccines against infection with Pseudomonas aeruginosa in mink (Lutreola vison)]. AB - Infections by Pseudomonas aeruginosa have caused losses on mink farms in recent years, particularly with a clinical manifestation of haemorrhagic pneumonia. This paper includes the first results of the practical use of the Czechoslovak soluble monovaccine of polyvalent action in the treatment of mink infected by Pseudomonas aeruginosa. The action of the vaccine is based on the protective effect of Original Endotoxin Protein (OEP), antigen common to all species of the genus Pseudomonas. After due testing, the vaccine was given to mink. Doses of 50, 200 and 500 micrograms, and in another series 50 and 200 micrograms of the vaccine were tested in subcutaneous administration at 0.2 ml volume in a 7-day interval. No adverse side-effects and reactions were observed in the animals. A protective action was demonstrated, resulting in a higher number of reared mink in comparison with the control groups. After vaccination, titres ranging from 2 to 160 were determined by the indirect haemagglutination method and from 320 to 164,000 by the RIA method. In 1984 the vaccine was used for practical treatment on a mink farm with the stock exposed to Pseudomonas aeruginosa infection (5551 mink were treated). In the vaccinated group losses amounted to 3.1% whereas in the control group the mortality level was above 17%. Vaccination was demonstrated to have a favourable effect and the vaccine was then preventively used on the same farm in the subsequent year; the treatment of 29,350 mink had the required protective effect. PMID- 3097915 TI - Evaluation of purified Theileria annulata sporozoite antigen from the tick Hyalomma anatolicum anatolicum. AB - Rabbits immunized with purified sporozoites from Hyalomma anatolicum anatolicum produced antibody to Theileria annulata specific antigens as measured by the indirect fluorescent antibody test. Nonspecific fluorescence which compounded the interpretation of the test was observed. Incorporation of Eriochrome black and Evans blue as a counterstain in the diluent buffer for the conjugate significantly reduced the background fluorescence. PMID- 3097916 TI - Detection of antigenic fractions from Brucella abortus S45/20 which bind to non agglutinating antibodies using electroblotting and enzyme-linked antibody probes. AB - Outer membrane antigens which bind to non-agglutinating antibodies (NAAb) elicited by smooth (S19) and rough (S45/20) Brucella abortus strains, were extracted from S45/20 by stirring in cold 2.5% NaCl and then analyzed by SDS PAGE, electroblotting and enzyme-linked antibody test. Eight bands were observed in the gel stained with Coomassie blue. Seven antigenic fractions were transferred to nitrocellulose by blotting. A 27-kd band was recognized by bovine anti-S45/20 non-agglutinating serum and not by purified NAAb against surface antigens. Bands 10 kd and 14.3 kd bound to bovine anti-S45/20 NAAb from calves immunized with either S19 or S45/20. A 12.0-kd band was recognized by the serum and NAAb from calves immunized with S45/20 but not by those injected with S19. There are thus antigenic fractions shared by S19 and S45/20 which bind in vitro to NAAb. PMID- 3097918 TI - [Concerns and methods for the recuperation of preschool children with psychomotor deficits]. PMID- 3097917 TI - Role of milk immunoglobulins in the Brucella milk ring test. AB - Milk immunoglobulins were extracted from the stained cream layer of positive milk ring tests from experimentally inoculated or naturally infected cows. IgA was always found, associated with IgM in most cases (15/17) and with IgG in a smaller number of cases (11/17). An additional incubation at 20 degrees C for 18 h gave clearer positive and negative results and a lower limit of detection than that of the usual milk ring test. PMID- 3097920 TI - [Culture and health interrelationship--the primary prevention of viral hepatitis]. PMID- 3097919 TI - [Medico-familial, social educational and health aspects of the single-parent family]. PMID- 3097921 TI - [Plea for Romanian education in the history of medicine]. PMID- 3097922 TI - [Early detection of cancer of the cervix uteri]. PMID- 3097923 TI - [Use of the venous reserve in the newborn infant]. PMID- 3097924 TI - [Monitoring of the child in a coma]. PMID- 3097925 TI - [Role of medical personnel in the dispensary care of premature children]. PMID- 3097926 TI - [Role of paramedical personnel in preparing preschool children for schooling]. PMID- 3097927 TI - [Actions to prevent tuberculosis morbidity in the university center of Cluj Napoca (1970-1984)]. PMID- 3097928 TI - [Role of hygienic measures in the dental care for pupils with incipient periodontopathies]. PMID- 3097929 TI - [Biorhythm in the educational practice of health personnel]. PMID- 3097930 TI - [Management of the diabetic coma in children]. PMID- 3097931 TI - [Nursing of the comatose child with organophosphorus substance poisoning]. PMID- 3097932 TI - [Double-contrast cystographic technic]. PMID- 3097933 TI - [The research implications of health education in the dynamic health culture of miners and the role of paramedical personnel]. PMID- 3097934 TI - [Role of paramedical personnel in the kinetotherapy for the recuperation of posttraumatic lesions of the extremities]. PMID- 3097935 TI - [Coma due to poisoning with chemical substances. The clinical characteristics and nursing]. PMID- 3097936 TI - [Recuperation from the sequelae of hand injuries in a department for children with motor deficiencies]. PMID- 3097937 TI - [Our experience in the prevention and treatment of pressure sores]. PMID- 3097938 TI - [Role of paramedical personnel in the psychoaffective development of preschool children (0-3 years) in the nursery]. PMID- 3097939 TI - [Role of the paramedical personnel of an obstetrics and gynecology department in preventing abortion]. PMID- 3097940 TI - [The role of nurseries in ensuring the continuity of nursing care and the harmonious development of the child]. PMID- 3097941 TI - [The contribution of paramedical personnel to the activities in the recuperation of acute myocardial infarct patients]. PMID- 3097943 TI - [The effect of the activities in modern industry on body posture during work time]. PMID- 3097942 TI - [Neuromotor recuperation of the psychomotor-handicapped institutionalized child]. PMID- 3097944 TI - [Implications of health education research in preventing chronic disease and the role of paramedical personnel]. PMID- 3097945 TI - [Music in the service of medicine--past, present and future. III. The tarantella and other musical remedies in the Middle Ages]. PMID- 3097946 TI - [The nurse in the year 2000]. PMID- 3097947 TI - Investigation into the origin of mouse liver sinusoidal cells. AB - The possibility that liver sinusoidal cells are derived from the bone-marrow was investigated in chimeric mice. H2k-positive bone-marrow cells from F1 (B10.BR X B10.D2) hybrid mice were transplanted into irradiated H2k-negative parental mice (B10.D2), and the liver examined immunohistochemically for the presence of H2k positive cells, with the help of an anti-H2k monoclonal antibody. With the passage of time (from the fifth week onwards), increasing numbers of transplanted bone-marrow cells enter the liver sinusoids, undergo alteration in their shape, and remain there, probably replacing sinusoidal lining cells. DNA-synthesising cells in the sinusoids were observed, suggesting, in addition, local cell proliferation. The replacement of sinusoidal cells from bone-marrow was greatly accelerated after liver damage had been induced by sublethal doses of endotoxin (LPS), and proliferation was also enhanced after treatment with LPS. These results strongly suggest that the bone-marrow participates in the replacement of liver sinusoidal cells. PMID- 3097948 TI - Alloxan-induced diabetes in the mouse: time course of pancreatic B-cell destruction as reflected in an increased islet vascular permeability. AB - The extent to which injections of the pancreatic B-cytotoxin alloxan in C57BL/Ks mice induced an increase in islet vascular permeability, and the time course of this increase, were studied. The vascular permeability was monitored by administration of the dye Monastral blue B, which is entrapped in leaky blood vessels with intact basement membranes. The islets were visualized by a freeze thawing technique which allows identification of stained islets. Not until four hours after the alloxan injections was there an increase in islet uptake of Monastral blue B when compared with saline-treated control animals. Thereafter the islet staining increased further. The process was accompanied by gradual development of hyperglycaemia and a reduction of number of the islets identified in the pancreatic preparations. It is concluded that alloxan causes an increase in islet vascular permeability, which appears to become manifest at a later stage than the cytotoxic B-cell degeneration. PMID- 3097949 TI - Reactivity of a monoclonal antibody recognizing an estrogen receptor regulated glycoprotein in relation to lectin histochemistry in breast cancer. AB - We have raised monoclonal antibodies against human milk fat globule membrane antigens and previously shown that one of them, called III D 5, recognises a glycoprotein associated with estrogen receptor activity of breast cancer. In immunoblotting it was shown that the molecule in human milk exclusively stained with III D 5 also binds peanut agglutinin (PNA) and Ricinus communis. In this study we correlate the staining of III D 5 and binding of lectins to tissue sections fixed in formalin and embedded in paraffin. Similar reactions were seen only with III D 5 and PNA. Our results suggest that III D 5 and PNA detect overlapping antigenic epitopes in mammary carcinoma. This is in keeping with previous results that PNA or III D 5 reactivity is correlated with estrogen receptor status of breast cancer. PMID- 3097950 TI - Ultrastructure, renin status, contractile and electrophysiological properties of the afferent glomerular arteriole in the rat hydronephrotic kidney. AB - Histological, ultrastructural, immunohistochemical, intravital microscopic and electrophysiological techniques have been applied to study experimental hydronephrosis in rats in order to assess its value as a preparation for the investigation of renal microcirculation and of the electrophysiological properties of the renin-containing juxtaglomerular (JG) cells of the afferent glomerular arteriole. As hydronephrosis develops, the kidney parenchyma becomes progressively thinner owing to tubular atrophy. Twelve weeks after ureteral ligature, this process results in a transparent tissue sheet of about 150-200 microns in thickness. In this preparation, the renal arterial tree as well as the glomeruli can be easily visualized for intravital microscopic studies, e.g. the determination of kidney vessel diameters, or the identification of JG cells for penetration with an intracellular microelectrode. In contrast to the tubular atrophy, the vascular system is well preserved, and the JG cells and the sympathetic axon terminals are ultrastructurally intact. This is also true for the glomeruli, except for a certain confluence of the podocyte foot processes and a thickening of the basal laminae. Renin immunostaining and kidney renin content in the hydronephrotic organ correspond to those in control kidneys. In addition, there are no differences in the plasma renin levels of hydronephrotic and control rats. Intravital microscopic observations reveal that the renal vascular tree reacts in a typical, concentration dependent manner to the vasoconstrictor agent angiotensin II, mainly at the level of the resistance vessels. Electrophysiological recordings from juxtaglomerular granulated cells show a high membrane potential (-60 mV), and spontaneous depolarizing junction potentials, owing to random transmitter release from the nerve terminals. Angiotensin II, an inhibitor of renin release, depolarizes JG cells reversibly. Hence, we may infer that the hydronephrotic rat kidney is a suitable model for in vivo studies of the renal microcirculation as well as for in vitro investigations of the electrophysiological properties of the media cells of the afferent glomerular arteriole. PMID- 3097951 TI - Experimental staphylococcal endocarditis and aortitis. Morphology of the initial colonization. AB - The initial colonization, by Staphylococcus aureus, of the catheter damaged aortic valve and aorta of the rabbit, was examined by light and electron microscopy at 15 min, 3 h and 24 h post inoculation (PI). At 15 min PI, the majority of bacteria (80%) were located on the lateral surfaces of the thrombic vegetations while 20% were attached directly to the connective tissue of the aortic valve and aorta in areas where the endothelial lining was disrupted. By 3 h the bacteria on the thrombic vegetations were covered by fibrin. At this time, the bacteria both within the vegetations and on the surface of the vasculature were undergoing multiplication to form small groups. The precipitation of thrombus around the bacteria attached to the surface of the aorta to form microscopic infected vegetations had occurred by 24 h PI. The colonizing bacteria did not elicit any phagocytic response. The colonization of the cardiovasculature by Staph. aureus did not necessarily require pre-existing vegetations. PMID- 3097952 TI - Lung deformation and macrophage displacement in smoke-exposed and normal mice (Mus musculus) following different fixation procedures. AB - Lung deformation (shrinkage or inflation) and displacement of pulmonary parenchymal macrophages were evaluated after immersion fixation, intratracheal instillation of fixative and lung lavage followed by intratracheal fixative instillation in cigarette smoke-exposed, sham-treated and control pallid male mice. Lung volume displacement and lung section and alveolar area analysis revealed that degree of deformation was uniform in lungs from all treatment groups fixed by immersion but not by instillation of fixative and fixative instillation following lavage. In situ pulmonary parenchymal macrophage number per lung section area of fixative-instilled lungs and lavaged lungs followed by fixative instillation was significantly greater than in those following immersion fixation in all corresponding treatment groups. A paucity of macrophages was noted in airways of fixative-instilled and lavaged followed by instillation of fixative lungs. Pulmonary macrophages were uniformly distributed throughout lung parenchyma following immersion fixation, while in fixative-instilled and lavaged prior to instillation of fixative lungs these cells tended to be concentrated in alveoli near terminal bronchioles. Lavage procedures removed an unknown portion of lung macrophages and appeared to ineffectively sample the pulmonary parenchymal macrophage population. Intratracheal instillation of fixative with or without prior lavage apparently alters the distribution of pulmonary macrophages by displacing airway phagocytes into the alveoli. Data reported suggest that fractional estimates of in situ lung parenchymal macrophage population can be obtained by counting the number of these cells per area of tissue from lungs fixed by immersion. PMID- 3097954 TI - Frequency and diagnostic value of the virus-like filamentous intranuclear inclusions in giant cell tumor of bone, not associated with Paget's disease. A study of 43 cases. AB - This paper deals with the paramyxovirus-like intranuclear inclusions observed in giant cells tumours of bone (GCTB). Twenty-one (49%) of 43 cases of GCTB (1977 1985), either fresh and/or cultured, show these ultrastructural inclusions. Fifty samples of various bone lesions in which giant cell lesions occurred, including aneurysmal cysts, hyperparathyroidism, osteoblastoma, human and rat osteopetrosis, GCT of tendon sheaths, and non skeletal granuloma were used as controls. These, together with 20 samples of normal bone (osteoclasts) did not contain intranuclear or intracytoplasmic viral inclusions. PMID- 3097953 TI - Quantitative analysis of T6-positive Langerhans cells in human skin cancers. AB - Epidermal Langerhans cells (LC) are required for antigen-presentation and for stimulating antigen-specific T cell activation. Similar functions may be important in the immune response to malignant skin tumours. Monoclonal anti-T6 antibody was used to examine LC population in basal and squamous cell carcinomas. Positive control labeling was performed with monoclonal anti-HLA-DR antibody. The number of T6-positive LC per mm2 of section was significantly decreased (p less than 0.01) in the tumour group in comparison with a sex and age-matched control group. The number of sun-exposed and covered regions was taken into consideration in each respective group. Within the tumours, LC were found more frequently in the tumour periphery and in most differentiated tumour areas (horn pearls) than in the rest of the tumour mass. T6-positive LC were rarely found in the dermis. Moreover, LC exhibited morphological changes in specimens from tumours. Staining with anti-HLA-DR antibody revealed less numerous positive cells within tumour nests than labeling with OKT6. A relationship between T6-positive LC quantities and extent of HLA-DR-positive infiltrates around tumours could not be established. These results suggest that immunological surveillance of neoantigen bearing tumour cells may be impaired in skin cancer. A reason for the reduced LC number may be an altered microenvironment in tumour tissue. PMID- 3097955 TI - Zonal aganglionosis. An enzyme and immunohistochemical study of two cases. AB - The existence of zonal aganglionosis, a rare variant of Hirschsprung's disease, is often questioned. An extensive enzyme and immunohistochemical study was performed on gut specimens of two patients presenting with bilious vomiting and abdominal distension to find evidence of the existence of double zonal aganglionosis and to characterize the abnormalities of the enteric nervous system. The hypotheses concerning the pathogenesis of this neurogenic disorder are reviewed. The results of our study confirm the existence of zonal aganglionosis. The clinical presentation may be similar to classical Hirschsprung's disease. PMID- 3097956 TI - Fatal epithelioid haemangioendothelioma presenting in the lung and liver. AB - Three patients with epithelioid haemangioendothelioma (EHE) are described. Two patients presented with pulmonary infiltrates and one with a hepatic tumour. All had a metastatic disease ending fatally, and all were autopsied. The diagnosis was confirmed either by immunohistological or ultrastructural analysis. All three tumours were cytokeratin-negative and vimentin-positive, while only two contained cells reacting with the antibody of factor VIII-related antigen. Electron microscopy of the third tumour revealed features indicating endothelial differentiation. A short literature review is also presented demonstrating that the outlook of EHE is worse than previously thought. PMID- 3097957 TI - Modulation of in vivo and in vitro transcription of bacteriophage phi 29 early genes. AB - The majority of early transcripts of the phi 29 bacteriophage are produced throughout the lytic cycle but the levels of a class of transcripts from the right end of the phi 29 genome are significantly reduced late in the infection. We have isolated a phage early protein which selectively interferes with the initiation in vitro of transcription from promoters at the right end of the phi 29 genome. The amino acid sequence of the purified inhibitory protein correlates to the sequence predicted from the phi 29 gene 6 reading frame. In addition the inhibitory protein was not detectable in cells infected with phage mutated in gene 6 and the decrease in transcription did not occur in vivo when nonpermissive cells were infected with phi 29(sus6). The results indicate that the gene 6 protein modulates transcription from the right side of the phi 29 genome. PMID- 3097958 TI - Signals in the phi 29 DNA-terminal protein template for the initiation of phage phi 29 DNA replication. AB - The protein-free terminal fragments HindIII B and L, from the left and right ends of phi 29 DNA, respectively, but not internal fragments of similar size, were active as templates in the formation of the p3-dAMP initiation complex in an in vitro system containing purified phi 29 terminal protein p3 and DNA polymerase p2, although the activity was lower than that obtained with the phi 29 DNA-p3 complex. These results indicate the existence of specific sequences at the ends of phi 29 DNA that allow the initiation of phi 29 DNA replication. The template activity of the protein-free terminal fragments was size dependent. The protein free single strands of the HindIII L fragment were much less active than the corresponding double-stranded fragment. Terminal protein-DNA complexes of phages PZA and phi 15, with a terminal protein closely related to the phi 29 protein p3, were more active as templates in the initiation reaction with the purified phi 29 proteins than the corresponding protein-free DNAs, as it happens in the case of phi 29. However, the terminal protein-DNA complexes of phages Nf, B103, and GA-1, with a terminal protein less related or unrelated to the phi 29 protein p3, were essentially inactive and became active after removal of the parental terminal protein. These results strongly suggest that the parental terminal protein is the major signal in the template for the initiation of phi 29 DNA replication. PMID- 3097959 TI - Hormonal regulation in in vitro fertilization. PMID- 3097960 TI - [Recurrence of esophageal cancer 9 years after radiotherapy with bremsstrahlung from a 25-MeV betatron]. PMID- 3097961 TI - [Adjuvant therapy of breast cancer patients]. AB - The paper discusses the state of the art in adjuvant treatment of breast cancer patients. The protocol of the randomized controlled study of the effectiveness of adjuvant chemohormonotherapy conducted at the Petrov Institute since January, 1985 is presented. It is suggested that all oncological institutions concerned should take part in a cooperative investigation to be carried out along the guidelines outlined in the protocol. PMID- 3097962 TI - The Medicare prospective payment system. Technical adjustments and the role of ProPAC. PMID- 3097963 TI - [Protective effect of nifedipine on histamine-induced bronchial spasm in patients responding and not responding to Intal treatment]. PMID- 3097964 TI - [Therapeutic strategies and tactics in parkinsonism]. AB - The main medication is Madopar and Sinemet; various additives are able to reduce the Dopa dose in order to avoid various side effects. Additives: Deprenil (Jumex), Amantadin derivatives) Symmetrell, PK Merz, Hofkomant). Furthermore Dopamin agonists (Umprel, Dopergin). Delpral for dyskinesias. Driving antidepressive in the morning (Noveril, Dixeran, Tofranil). In the evening tranquillizing antidepressive like Tryptizol, Saroten, Sinequan, Ludiomil, Tolvon. Anticholinergica for Salivation, L-Tryptophan in hot environment. PMID- 3097965 TI - [Medicamentous strategy for improving the quality of life in the senescence]. AB - The striatum, in which the nigrostriatal dopaminergic neurons terminate, contains the highest amount of dopamine DA) in the brain. DA, released in the striatum, plays the rate limiting role in the control of motor functions by continuously inhibiting the release of acetylcholine (ACh) from the cholinergic interneurons of the caudate nucleus. DA content of the human caudate nucleus decreases by 13% per decade over the age of 45. Parkinson's disease seems to be a kind of selective, highly accelerated 'premature aging' of the nigrostriatal dopaminergic system, and the DA content of this neuron system shrinks within a short time to less than 10% of the normal level in the premorbid state. Clinical symptoms occur when the striatum loses more than 70% of its DA content. The chemical lesioning of the nigrostriatal dopaminergic neuron in the rat by 6-OH-dopamine (6-OHDA) leads to an increase of cholinergic activity in the striatum. The striatum taken from a rat pretreated with 6-OH dopamine is a useful experimental model for the rapid screening of compounds with potential therapeutic benefit in Parkinson's disease. A more specific neurotoxin than 6-OHDA is 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) which kills the cells in the substantia nigra with high specificity and induces rapidly parkinsonian-like condition in men and monkeys. ( )Deprenyl, the selective inhibitor of B-type MAO protects the striatum from the neurotoxic effects of 6-OHDA and MPTP. The amount of ACh released from the striatum of the rat increases from 372.8 +/- 31.4 to 746.5 +/- 44.0 pmol/g/min in 6-OHDA treated rats, it remains normal (371.1 +/- 34.7) if (-)deprenyl is given 30 minutes before 6-OHDA administration, hut is further increased (956.3 +/- 79.3 pmol/g/min), if clorgyline os injected 30 minutes before 6-OHDA. (-)Deprenyl prevents in a similar manner the neurotoxicity of MPTP in monkeys, whereas clorgyline, the selective inhibitor of MAO-A, is ineffective. The most important effect of deprenyl in the brain is the sensitization of dopaminergic neurons to physiological and pharmacological influences without eliciting an acute increase in dopaminergic activity. The effect of deprenyl is due, on the one hand, to the inhibition of MAO-B and, on the other hand, to inhibition of the uptake of dopamine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3097966 TI - Resistance of vectors and reservoirs of disease to pesticides. Tenth report of the WHO Expert Committee on Vector Biology and Control. PMID- 3097967 TI - Joint FAO/WHO expert committee on brucellosis. PMID- 3097968 TI - Genetic and biochemical control of grain protein synthesis in normal and high lysine cereals. PMID- 3097969 TI - [Bacteriological diagnosis within the scope of tuberculosis control]. PMID- 3097970 TI - [Effect of glucagon on intestinal microcirculation]. AB - Examinations in rats were carried out for investigating the glucagon effect on the bowel microcirculation. After intramuscular injection of glucagon an increase of the pO2, a decrease of the pCO2, and a consistent pH value were observed in the mesenteric vein. The results showed that by means of glucagon arteriovenous shunts of the bowel mucosa were opened. This leads to the exclusion of the capillary network in the villi. PMID- 3097971 TI - [Diverticula and aneurysms of the right ventricle: classification, clinical aspects and therapy]. PMID- 3097972 TI - [Improvement in the method of treating scabies with benzyl benzoate]. PMID- 3097973 TI - [Diagnosis by culturing Ureaplasma urealyticum and gonococcus in patients with urogenital pathology]. PMID- 3097974 TI - [Computed tomographic assessment of stenoses of the cervical spinal canal]. PMID- 3097975 TI - [Morphologic and functional changes in the shoulder region following acromioclavicular separation]. PMID- 3097976 TI - [Use of the Ilizarov apparatus in severe injuries of the extremities]. PMID- 3097977 TI - [Percutaneous drill wire osteosynthesis of fractures of the proximal humerus]. PMID- 3097978 TI - [Behavior of osteosynthesis screws in the interval between implantation and explantation]. PMID- 3097980 TI - [Pro and con MAST--the state of the art 1985]. PMID- 3097979 TI - [Multiple injuries in burn patients]. PMID- 3097981 TI - [Results of surgery of acromioclavicular luxations (Tossy III)]. PMID- 3097982 TI - [Fat embolism and diaphyseal fracture of the femur--prospective study]. PMID- 3097983 TI - [The Injury Severity Score and outcome in accident victims requiring intensive care]. PMID- 3097984 TI - [Staphylococcus albus, a present-day pathogen in traumatology/orthopedics]. PMID- 3097985 TI - [Medical, social and economic aspects of 2-wheeled vehicle accidents]. PMID- 3097986 TI - [Long-term results of surgery of acromioclavicular luxations using Bosworth's technic]. PMID- 3097988 TI - Biochemical properties of fibrinogen binding protein (clumping factor) of the staphylococcal cell surface. AB - The staphylococcal fibrinogen binding protein of a strain of coagulase-negative Staphylococcus aureus was purified 229 fold in terms of the haemagglutination unit compared to the starting material by affinity chromatography on fibrinogen Sepharose. By polyacrylamide gel electrophoresis in both reduced and unreduced gels, the protein showed one major band and minor bands with relative molecular masses of 62,000, 61,000, and 59,000, respectively. The isoelectric point was between 10.2 and 10.8 determined by isoelectric focusing in polyacrylamide gel. By the agar diffusion test one band was obtained against anti-whole cell rabbit serum. Amino acid analysis of fibrinogen binding protein showed glycine, glutamic acid, lysine, alanine, aspartic acid, and arginine as the major components. Protein A or teichoic acid extracted from the homologous strain did not show fibrinogen binding activity assayed by haemagglutination and anti-fibrinogen binding activity of anti-whole cell Fab. The amount of the fibrinogen binding protein to absorb the activity of anti-whole cell Fab was decreased to 1/60 of that of the starting material. Sheep red blood cells coated with the fibrinogen binding protein agglutinated in 0.001% (w/v) fibrinogen solution. PMID- 3097987 TI - Metal analogues of mycobactin and exochelin fail to act as effective antimycobacterial agents. AB - Mycobactins and exochelins from mycobacteria formed complexes with many heavy metals in the absence of iron. Although many of these complexes affected the growth of M. tuberculosis and M. avium in laboratory culture medium and in serum the complexes were not stable enough in the presence of iron, which displaced the metal ion, to be of value as specific antimycobacterial agents. PMID- 3097989 TI - Action of colistin (polymyxin E) on the lytic cycle of the mycobacteriophage D29 in Mycobacterium tuberculosis. AB - The antibiotic colistin (polymyxin E) inhibited the lytic cycle of the mycobacteriophage D29 in the tubercle bacilli, but not the D29 adsorption. The protein and nucleic acid synthesis in D29-infected bacteria were not affected significantly. The inhibitory activity was reversed by washing off the antibiotic, and by addition of Ca++, but not in media made iso-osmotic by addition of NaCl or sucrose. Transmission electron microscopy revealed an asymmetric to symmetric transition in the staining profile of the cytoplasmic membrane. Though no mature phage particles were ever observed in colistin treated, D29-infected tubercle bacilli, loosely arranged aggregates resembling phage proheads were occasionally found. Judging from the above data, it was concluded that colistin inhibited D29 lytic cycle by causing molecular displacements in the inner leaflet of the cytoplasmic membrane, and consequently, the binding sites for D29 structural proteins were not available. PMID- 3097990 TI - [Virulence of Listeria welshimeri]. AB - The species L. welshimeri consists of non-pathogenic bacteria. 16 different strains which were characterized biochemically were unable to multiply within adult NMRI mice after injection of a high dose of about 10(7) bacteria. Even macrophage depleted animals, which were obtained by treatment with highmolecular dextran sulfate, could eliminate L. welshimeri. 5 day old baby mice were resistant against L. welshimeri. L. innocua was as avirulent as L. welshimeri, whereas L. monocytogenes was virulent, since these bacteria multiplied in adult animals, killed macrophage depleted adult mice as well as baby mice after injection of low doses. PMID- 3097991 TI - Further histochemical aspects of the development of the fetal porcine epidermis. PMID- 3097992 TI - Clinical findings in experimental lesions of the bovine spinal cord and dorsal rootlets. PMID- 3097993 TI - [Protein content and protein fractions in the synovia and serum of cattle with healthy joints and cattle with aseptic or infected arthritis]. PMID- 3097994 TI - [Cause of nutrition-induced muscular dystrophy in suckling lambs in Turkey]. PMID- 3097995 TI - [Measurement of mucociliary clearance in dogs and rabbits in vivo]. PMID- 3097996 TI - Rectovaginal constriction in Jersey cattle. VII. Anatomical characterization of the constriction rings in the anal and vestibular canals. PMID- 3097997 TI - [Videomicrography--a possibility for the objective determination of the motility of bull sperm]. PMID- 3097998 TI - Aerobic and anaerobic metabolism of the musculus extensor carpi radialis and the musculus flexor digitorum superficialis in calves with arthrogryposis multiplex congenita (AMC) of both forelimbs. PMID- 3097999 TI - Xylose absorption in adult sheep and associated kinetics. PMID- 3098001 TI - Demonstration of persistent viral haemorrhagic septicaemia (VHS) virus in rainbow trout after experimental waterborne infection. PMID- 3098000 TI - [O-serovars and antibiotic sensitivities in strains of Pseudomonas aeruginosa of human and animal origin]. PMID- 3098002 TI - [Formation of microvesicles in meningococcal cells during batch cultivation]. AB - Both surface and intracytoplasmic vesiculae have been shown to appear in meningococcal cells, strains 132, 125, and 133 belonging, respectively, to serogroups A, B, and C, in the process of batch cultivation. The surface microvesiculae are formed from the outer membrane of the cell wall during the whole process of batch cultivation. The intracytoplasmic membrane structures are formed in the process of cell autolysis. As revealed in this investigation, the strains under study, irrespective of their serogroup, are characterized by similar mechanisms of the formation of microvesiculae. The surface microvesiculae have been found to fall into three main types: monolamellar, multilamellar, and large spheroid bodies. The presence of specific functional features in each type of surface microvesiculae is suggested, as these microvesiculae, besides having their characteristic ultrastructure, differ in their contents. The attenuated culture of meningococcal strain 133, whose cells are notable among other strains under study for their more active (quantitatively) formation of microvesiculae, has been shown to have the highest toxicity for rabbits. PMID- 3098003 TI - [Characteristics of the functional antigens of Neisseria meningitidis group B]. AB - The work deals with the characterization of the functional antigens of N. meningitidis, group B. Analysis of the total extract of N. meningitidis strain B16B6 with the use of sera obtained from patients with meningococcal infection, nasopharyngitis, salmonellosis, as well as from meningococcus carriers and healthy donors, by immune blotting techniques and the affinity isolation of the functional antigens indicate that protein antigen with a molecular weight of 13 15 kd is the main common antigen inducing the formation of antibodies in patients with meningococcal infection. PMID- 3098004 TI - [Determination of protein A I staphylococcus aureus strains isolated from monkeys]. AB - Protein A content in Staphylococcus aureus isolated from 6 species of monkeys at the Sukhumi Monkey Nursery has been studied. Protein A has been detected in 73% of the studied strains. One strain isolated from a rhesus macaque has been found to release high amounts of protein A into the environment. PMID- 3098005 TI - [Isolation and characteristics of a specific polysaccharide of group-B meningococci]. AB - The optimum conditions for the isolation and purification of the specific polysaccharide of group B meningococci have been developed. The advantages of the use of synthetic culture media for growing the initial bacterial culture have been demonstrated. The purified polysaccharides have been found to contain about 70% of sialic acid and less than 1% of protein and nucleic acid admixtures. The molecular parameters of group B polysaccharide depended on the growth phase of the bacterial culture. The most valuable culture was obtained at the exponential phase of growth. High serological activity and specificity of the polysaccharide in the passive hemagglutination test recommend it for studies on the development of diagnostic and prophylactic preparations. PMID- 3098006 TI - [Characteristics of blastolysin preparations in their ability to inhibit hemagglutination caused by bacteria of the genus Lactobacillus]. AB - Anabol and blastolysin preparations obtained from L. bulgaricus may contain surface structural components of the initial strain with adhesion activity; of these, one is similar in specificity to L. casei adhesin and the other, to L. plantarum adhesin. The antigenic activity of anabol and blastolysin, evaluated in the immunodiffusion test, does not correlate with their capacity for binding the receptors of susceptible bacterial cells, determined in the Lactobacillus-induced hemagglutination inhibition test. PMID- 3098007 TI - [Immunologic properties of purified and complex preparations of group-B meningococcal polysaccharide]. AB - The complex preparations of group B meningococcal polysaccharide have been found to be capable of inducing primary immune response in mice, while purified group B polysaccharide has proved to be immunologically inert. As revealed in this investigation, the intravenous injection to mice of the optimum doses of the complex preparation of group B polysaccharide leads to the increased number of specific B-antibody-forming cells in their spleens and to a rise in B-antibody titers in their sera; besides, the time course of the process has been studied. Both preparations have been found capable of forming the immunological memory in mice if booster immunization is made with the complex preparation of group B polysaccharide. The immunological inertness of purified group B polysaccharide is attributed, supposedly, to the action of some specific suppressor mechanism. Considering the pronounced antigenic activity of the complex preparation of group B polysaccharide and the insignificant admixture of endotoxin in this preparation, the suitability of its future use as vaccine for the prophylaxis of meningitis caused by group B meningococcus is indicated and the tentative immunization schedules are discussed. PMID- 3098008 TI - [Diagnostic test system for detecting the meningococcal antigen by erythro immunoadsorption]. AB - The authors have developed a test-system for detection of group A meningococcal polysaccharide, based on the sandwich erythro-immunoadsorption ultra microtechnique with the use of the Terasaki plates as a solid-phase carrier. The system, equivalent to ELISA in its high sensitivity and specificity, is more rapid and less expensive, permitting the detection of 1 mg/ml of the antigen in 20 microliter of the tested liquid within an hour. The results of the study of CSF samples from 28 patients with meningococcal infection were in good correlation with the ELISA results. The new test-system is recommended for practical use as a routine technique for the specific diagnosis of meningococcal meningitis and for the control of the effectiveness of the treatment. PMID- 3098009 TI - [Dynamics of the contamination of mice during the treatment of burn sepsis due to Pseudomonas aeruginosa using tobramycin alone or combined with active and passive immunization]. AB - An experimental study was made with a view to finding out the possible bacteriological advantages of the combined use of tobramycin (Tb) and P. aeruginosa corpuscular polyvalent vaccine (PaCPV) or P. aeruginosa hyperimmune plasma (PaHIP) in burn sepsis caused by P. aeruginosa. The use of the median therapeutic dose of Tb (2.5 mg/kg body weight per day), alone or in combination with immunopreparations, ensured the survival rate of the animals equal to 100%. The contamination of the body with P. aeruginosa after treatment with Tb and PaHIP or PaCPV was lower than after the administration of Tb alone, this phenomenon becoming manifest starting from day 5 of observation in the first case and from day 10 in the second case. The combined use of Tb and immunopreparations (PaCPV or PaHIP) in acute P. aeruginosa infection proved to be more effective than treatment with Tb alone. PMID- 3098010 TI - Comparison of heterogeneous nuclear ribonucleoprotein particles of the developing rat liver. AB - hnRNP monoparticles were isolated from livers of newborn (1 day), 7, 10, 11, 14, 21, 28 days old and adult rats, and their sedimentation properties, buoyant densities and protein composition were compared. There were observable differences neither in sedimentation nor in buoyant density among the particles isolated from livers of rats of different ages. The hnRNP particles derived from every stage of ages sedimented in the 30-50S zone of sucrose gradient with a peak at about 38S. Glutaraldehyde fixed particles in CsCl gradients banded at 1.36 g/cm3 which corresponds to about 80% of protein in the particles. Urea/sodium dodecyl sulfate/polyacrylamide gel electrophoresis of hnRNP proteins demonstrated 19 polypeptides in the 35,000-140,000 Mr range. Three main polypeptides in hnRNP of every group of animals could be observed with apparent Mr of 39,000, 43,000 and 46,000. In the minor components only quantitative differences could be seen in the different age groups with the exception of a 35,000-Mr polypeptide which appeared on the 11th day after the birth. PMID- 3098011 TI - The effect of alpha-difluoromethylornithine on ornithine decarboxylase activity in compensatory growth of mouse lung. AB - After removing the left upper lobe, the remaining lung of mice undergoes compensatory growth. Increased ornithine decarboxylase activity is characteristic of the process. The effect of alpha-difluoromethylornithine was studied on the ornithine decarboxylase (E.C.4.1.1.17.) activity and on the lung growth in mice after lobectomy. Although a single injection of alpha-difluoromethylornithine inhibited ornithine decarboxylase activity, the compensatory growth of lung still occurred in spite of continuous alpha-difluoromethylornithine treatment. This suggests that polyamines, indispensable for compensatory growth, may be supplied by other sources. PMID- 3098012 TI - Possibilities of biological energy production. AB - From the numerous possibilities of biological solar energy transduction the production of hydrogen was selected in our laboratory. There are two forms of H2 production: from biomass with enzymes (formate-hydrogen lyase and hydrogenase enzymes) and the exploitation of some living systems or their analogs to evolve H2 from water upon solar irradiation. To approach the first problem, a bacterial strain and a hydrogenase (H2ase) enzyme of good parameters were isolated. The system composed produced H2 from biomass with an energetic efficiency of 10-12 per cent. Dealing with the second task, by changing some environmental factors we succeeded to increase by a factor of 15 the quantity of H2 produced by Anabeana cylindrica from water in light. It is clear from these studies that further research is needed to understand better the mechanism and regulation of biological H2 production. The aim of this research is to utilize it as an economically feasible and environmentally harmless energy source. PMID- 3098013 TI - Changes in insulin receptor functions of the erythrocyte by treatment of non insulin-dependent diabetes mellitus (NIDDM) patients with glibenclamide and diet control. AB - The insulin binding of erythrocytes from: (i) fifteen age-matched normal subjects, (ii) ten untreated NIDDM patients and (iii) fifteen treated (glibenclamide + hypocaloric diet) NIDDM patients (all males) has been studied. A significant decrease in specific insulin binding was observed in group (ii) which improved in cases controlled after treatment (group iii). Scatchard analysis of the results suggested that changes in insulin binding were due to alteration in the number of insulin receptors on erythrocytes. The number of insulin receptors/cell was 471 in normals, 160 in diabetics and 282 in treated diabetic subjects. No significant change in the binding affinity was observed in the three groups (1.0 X 10(8), 1.2 X 10(8) and 1.1 X 10(8) M-1 in normal subjects, untreated diabetics and treated diabetics, respectively). PMID- 3098014 TI - Failure of GnRH analogue to inhibit serum concentrations of testosterone and 17 alpha-hydroxyprogesterone in hCG-substituted hypogonadotropic hypogonadism. AB - Gonadotropin-releasing hormone analogues (GnRH-A) induce inhibition of testicular function and reduction of serum testosterone (T) in man, but the mechanism involved is still debatable. To elucidate it we studied six patients with hypogonadotropic hypogonadism (HH) in chronic substitution with hCG for correction of androgen deficiency symptoms, and evaluated the effect of addition of GnRH-A to the hCG therapy on plasma levels of T and 17 alpha hydroxyprogesterone (17 OHP). All patients were treated with 1000 U of hCG in every 3rd day for 24 weeks. After 8 weeks of this regimen, GnRH-A, Buserelin (D Ser-TBU-EA-LHRH), 200 micrograms per day sc, was added and given for 8 weeks. After cessation of analogue administration patients were followed for 8 further weeks. The levels of the two steroids did not differ markedly in the pre- and post-GnRH-A period. GnRH-A given for two months did not lower T or 17 OHP levels as in eugonadal men after similar treatment. The median T concentrations during GnRH-A tended to be increased, with plasma values higher (P less than 0.025) than the peak values observed during hCG alone. Since administration of Buserelin did not inhibit hCG-sustained steroid levels in these HH patients, it is conceivable that GnRH-A may have lacked a direct inhibitory gonadal effect in such experimental conditions. PMID- 3098016 TI - Decreased serum thyroglobulin levels in the late stage of pregnancy. AB - Serum thyroglobulin levels were serially measured in 25 normal pregnant women to evaluate thyroidal activity during normal pregnancy. Measurements included serum T3, T4, free T4, TBG, and TSH. Tg and FT4 levels were found to be decreased in the third trimester when compared with those of the first trimester and with those of normal non-pregnant individuals (P less than 0.01). TSH levels were higher than normal in pregnant women at all stages of pregnancy, with a significant rise at the third trimester. These findings suggest the presence of a subclinical hypothyroid state in the late stage of normal pregnancy. PMID- 3098015 TI - Similar isoelectric profiles of FSH from gonadotroph cell adenomas and non adenomatous pituitaries. AB - Heterogeneity of intact FSH in human pituitary tissue was evaluated by the column isoelectric focusing technique, chromatofocusing. FSH was examined from three autopsy pituitaries, one piece of apparently normal pituitary obtained at surgery, three purified FSH preparation, and four gonadotroph cell adenomas. FSH from all of these sources was found to exist in multiple isoelectric forms. FSH from the gonadotroph cell adenomas exhibited chromatofocusing profiles that were similar, both in the range of pI's and the relative proportions of the FSH isohormones, to those of the non-adenomatous pituitaries. We conclude that gonadotroph cell adenomas produce a population of FSH that is qualitatively normal although quantitatively excessive. PMID- 3098017 TI - Testosterone stimulates pituitary and serum FSH in GnRH antagonist-suppressed rats. AB - Thirty days of continuous treatment of adult male rats with 35 micrograms/day of the potent GnRH antagonist, (N-Ac-D-Nal (2)1, D-pCl-Phe2, D-Trp3, D-hArg (Et2)6, D-Ala10)-GnRH (RS-68439) reduced serum FSH to values below the limit of detection of the assay. Testosterone supplementation in the form of subcutaneous testosterone-filled silastic capsule implants present during an additional 30 days of GnRH antagonist administration restored serum FSH to values comparable to those observed after vehicle treatment. Pituitary FSH content, which was substantially reduced after GnRH antagonist treatment, was completely restored after concurrent testosterone supplementation. These results show that, under conditions of GnRH receptor blockade, testosterone is capable of stimulating pituitary and serum FSH in adult male rats. PMID- 3098018 TI - Gonadotropin responses to low dose pulsatile administration of GnRH in a case of anosmia with hypogonadotropic hypogonadism associated with gonadal dysgenesis 47 XXY. AB - A 25 year old man presented hypogonadotropic hypogonadism with complete anosmia (Kallman's syndrome). His chromosomic type was 47 XXY (Klinefelter's syndrome). Clinical findings were: height 183 cm, weight 62 kg, increased length of lower limbs, P2-A2 pilosity and micropenis. Only a left testis was present (1.5-1.5 cm). Bone age was 15. Testicular biopsy showed that the signs were more related to the gonadotropic deficit than to the gonadal dysgenesis; tubular hyalinization was not observed. Plasma levels of testosterone and oestradiol were very low. Plasma gonadotropin levels were below normal ranges and did not respond to an infusion test of GnRH. GnRH was administered iv every 90 min for 3 weeks by an auto syringe infusion pump and induced a pulsatile response of FSH and LH. Plasma levels of testosterone and oestradiol were unaffected. It may be concluded that the results of pulsatile injection of GnRH confirmed in this patient a unique association of Kallmann's syndrome with complete 47 XXY Klinefelter's syndrome. PMID- 3098019 TI - Changes in blood glucose, liver glycogen, ketone bodies and plasma insulin in suckling rats treated with a single high cortisol dose one day after birth. AB - Rats treated with cortisol, 0.5 mg one day after birth, show a decrease in body and organ weight and a decrease in pituitary TSH and GH when compared to controls together with a lack of response of TSH to TRH. These alterations have been previously found in animals treated with large doses of thyroxine, neo-T4 syndrome, in both populations a brain underdevelopment has been observed. Plasma insulin in cortisol-treated animals was higher (P less than 0.01) than in the controls at 8 and 12 days of life and lower at 22 days (P less than 0.001). Plasma ketone bodies were increased significantly at 8 but not at 12 and 22 days of life in the cortisol treated animals. Liver glycogen was higher than in controls at 2, 4, 6 days of life and lower at 8, 12 and 22 days. Blood glucose was higher than in controls at 2, 4 days and lower at 6, 8, 12 and 22 days of life. The timing of metabolic events is important for the adaptation and development of the post-natal animal. The perturbances in carbohydrate metabolism in suckling rats were also previously found in neo-T4 rats during the period when the brain growth spurt and energy need are the greatest; but in the rats treated with cortisol the timing of the alterations was different. This different timing of the metabolic perturbances could correlate with a different maturation in cerebral tissue found in histological studies in the two populations. PMID- 3098021 TI - Diagnostic value of immunological leukemia phenotyping. AB - The diagnostic value of immunological leukemia phenotyping using a panel of reagents in immunofluorescence assays was assessed in 309 consecutive patients. The cells from 307 patients could be clearly phenotyped and assigned to one of the subgroups with a definite immunophenotype. Each phenotype was characterized by a distinct marker profile. A simplified classification scheme based on surface antigen expression is presented. A combination of complementary reagents ('first panel') was used for the first-line screening. The application of selected reagents from the 'second panel' allowed for further subtyping and confirmation of the primary diagnosis. The contribution of different key reagents to the identification of distinct immunophenotypes is discussed. Multiple marker analysis, i.e. the combination of information from several disciplines, is a necessary and very useful tool in the routine investigation of patients with hematopoietic malignancies. PMID- 3098020 TI - Gamete intrafallopian transfer (GIFT): use of minilaparotomy and an individualized regimen of induction of follicular development. AB - The performance of the gamete intrafallopian transfer (GIFT) technique, utilizing an individualized regimen of follicular induction and minilaparotomy in 45 patients with infertility of varying etiologies is reported. The induction regimen consisted of the administration of clomiphene citrate, 100 mg, from day 3 to day 7, and 150 IU FSH/LH (human menopausal gonadotropin [hMG]) from day 6 on. Human chorionic gonadotropin (hCG; 10,000 IU) was administered when at least two follicles measured 16 mm or more in diameter and when serum estradiol (E2) measurement revealed levels of 350 pg/ml per each main follicle. Up to two oocytes and 100,000 motile sperm were transferred to the fallopian tubes via the fimbria, using a catheter. Of the 45 cases, 13 became pregnant by clinical criteria (29 per cent). Of these 13 pregnancies, nine continued to term (69 per cent), three miscarried spontaneously (12 per cent) and one was an ectopic (7 per cent). Of the nine pregnancies that continued to term, five (55 per cent) were twins. Details of the GIFT procedure as well the preliminary non-human primate research studies that led to the development of the GIFT technique are discussed. It is concluded that GIFT is an excellent alternative to in vitro fertilization and embryo transfer (IVF; ET) in all cases of infertility that failed to conceive using conventional forms of therapy and in which the female partner presents at least one normal fallopian tube. PMID- 3098022 TI - CD-15 antigen detected by the VIM-D5 monoclonal antibody for prediction of ability to achieve complete remission in acute nonlymphocytic leukemia. AB - The prognostic value of cell differentiation antigens detected with the monoclonal antibodies of VI series was studied in 242 cases of acute nonlymphoblastic leukemia (ANLL) treated in 7 cooperating centers. A significantly higher complete remission rate was observed in patients with a higher expression of CD-15 antigen detected by VIM-D5 antibody than in those with lower values. These significant differences were proved when comparing subgroups with VIM-D5 positivity of blastic cells less than 15 and much greater than 15% (p less than 0.01) as well as in the subgroups with values less than 50% (median value) and greater than or equal to 50% (p less than 0.02). Our studies suggest the VIM-D5 positivity of ANLL cells to be favourable prognostic factor predicting the ability to achieve complete remission. Further studies are needed to establish whether the expression of the VIM-D5-defined antigen may serve as a prognostic factor related to survival. PMID- 3098023 TI - Prognostic significance of in vitro marrow culture growth pattern in untreated acute nonlymphocytic leukemia. AB - The growth pattern of marrow cells in agar culture was studied in 90 adult patients with acute nonlymphocytic leukemia (ANLL) at diagnosis. We classified the abnormal growth patterns into 4 groups, A: no growth, B: decreased growth, C: excessive microcluster formation and D: excessive cluster growth with more than 20 colonies. There was a good correlation between growth pattern and FAB subtype. A predominance of group A growth was observed in M1, while group B growth was found in 50% of patients with M2 and M5. No relationships between the growth patterns and other clinical parameters were detected. Sixty-six patients were evaluable for treatment outcome. The growth pattern significantly correlated with complete remission rate. The remission rates were 52, 87, 80, and 25% for patients with group A, B, C and D growth, respectively. Analyses of remission duration and survival curves showed significant differences among the different growth patterns. Patients with D growth experienced a shorter remission duration and a lower survival rate than other groups. These results indicate that the in vitro culture growth pattern in untreated ANLL is of prognostic significance in predicting the response to therapy. PMID- 3098024 TI - Composite lymphoma (Hodgkin's and non-Hodgkin's) of the spleen in a previously untreated patient. AB - Clinicopathologic features of a patient presenting with Hodgkin's disease and histiocytic lymphoma in the spleen are presented. To our knowledge, this is the third case report of such an association. Incidence, clinicopathologic features and histogenetic concepts of composite lymphoma are discussed. PMID- 3098025 TI - Erythrocyte enzymes in polycythemia vera: a comparison to erythrocyte enzyme activities of patients with iron deficiency anemia. AB - Fifteen cytoplasmic erythrocyte enzyme activities were determined in patients with polycythemia vera (PV), iron deficiency anemia (IDA), and a group of healthy volunteers. Among the PV patients, the erythrocyte enzyme activities were compared between 2 groups: patients treated solely with phlebotomy and patients treated with phlebotomy, Myleran (busulfan) and/or radioactive phosphorus 32P. Significant reduction in glutathione reductase activity was found in the PV group of patients. This activity was normalized by the addition of flavin adenine dinucleotide. In contrast to previous reports, no other enzyme activity was found to be significantly reduced. The activities of the enzymes known to be age dependent were significantly elevated in all the groups tested except for phosphofructokinase and 3-phosphoglycerate mutase. The former was not elevated in any of the groups studied, while the latter was elevated only in the group of patients treated with Myleran and/or 32P. It was concluded that glutathione reductase (GR) deficiency is the only acquired enzyme deficiency in our group of PV patients and that radiation and chemotherapy did not induce further reduction in the activities of any of the enzymes tested. The possible involvement of GR deficiency in the etiology of the red cell life span shortening was discussed. PMID- 3098026 TI - Effect of intestinal flora modulation by oral polymyxin treatment on hemopoietic stem cell kinetics in mice. AB - After oral treatment with polymyxin for only 1 day, fecal aerobic gram-negative bacteria were found completely suppressed in C3H/Law mice. Complete suppression of aerobic gram-negative bacteria was accompanied by a reduction of the fecal endotoxin concentration from 100 to 10 micrograms endotoxin per gram of feces as measured with the Limulus amebocyte lysate assay. Oral administration of polymyxin affected hemopoietic stem cell kinetics at different stages. The kinetic behavior of hemopoietic stem cells was determined as the in vivo sensitivity to the S phase specific cytostatic drug hydroxyurea. The hydroxyurea kill of bone marrow spleen colony-forming cells diminished not significantly (p less than 0.10) from 14 to 4% after 2 days of polymyxin treatment. Already after 1 day of treatment the hydroxyurea kill of bone marrow progenitor cells forming granulocyte-macrophage colonies in vitro decreased from 29 to 7% (p less than 0.05). It took 8 days of treatment before the hydroxyurea kill of splenic granulocyte-macrophage colonies was found reduced from 53 to 14% (p less than 0.001). The decreased susceptibility of hemopoietic stem cells to hydroxyurea during polymyxin treatment appears to argue for a role of intestinal aerobic gram negative bacteria in the regulation of hemopoiesis, probably mediated by endotoxin. PMID- 3098027 TI - The use of insulin-enriched culture medium and human-human hybridoma formation: a preliminary study. AB - Human lymphoblastoid cell line WI-L2-729-HFZ was fused with human lymph-node lymphocytes in one fusion and with human spleen cells in another fusion to generate human-human hybridomas. In both, increasing doses of insulin were added to the HAT medium immediately after the PEG-mediated cell fusion (10(-1)-10(-5) IU/ml) and the number of clones formed was determined 3 weeks later. 10(-3) IU/ml of insulin resulted in a 2- to 5-fold increase in the number of clones generated compared to the control plates. In view of the known difficulties in generating high-yield human-human hybridoma fusions, it is suggested that the use of insulin supplemented HAT medium may provide a more efficient way in obtaining such clones. PMID- 3098029 TI - Missing Y chromosome in 2 patients with chronic myelocytic leukemia. AB - 2 cases of chronic myelocytic leukemia (CML) without Y chromosome are reported. One is a 45-year-old man with Philadelphia-positive CML, and the other a 74-year old patient with Philadelphia-negative CML. Cytogenetic analysis of bone marrow and peripheral blood cultures with and without PHA stimulation was carried out. The Philadelphia-positive patient died after 15 months, whereas in the case of the Philadelphia-negative patient, the survival time of 27 months exceeded the median survival time usually reported for Philadelphia-negative CML patients, thus indicating a prognostic relevance of the missing Y chromosome. PMID- 3098028 TI - Red cell pits appear preferentially in old cells after splenectomy. AB - The percentage of erythrocytes with pits in the peripheral blood after splenectomy was followed in 4 patients. The pit counts started to increase soon after surgery and were above 20% on the 20th postsplenectomy day. The results demonstrate that the majority of pits developed in circulating erythrocytes. Two other patients with autoimmune hemolytic anemia who had failed to respond to splenectomy presented an increase of pit counts from 5.5-13% to 29.8-47.4%, accompanying an increase of erythrocyte life-span during corticosteroid treatment. The data indicate that pits are formed preferentially in older erythrocytes. PMID- 3098030 TI - Aspergillus vegetative endocarditis complicated with schizocytic hemolytic anemia in a patient with acute lymphocytic leukemia. AB - Aspergillus vegetative endocarditis developing in a patient with acute lymphocytic leukemia during the phase of hematological remission has led to a fatal outcome, complicated with severe hemolytic anemia with red cell fragmentation. Systemic aspergillosis may involve heart valves with underlying disorders, but seldom affects intact valves even in severely compromised hosts. Among such rare cases so far reported, only 2 cases have been documented in acute leukemia, despite a huge prevalence of pulmonary and systemic aspergillosis in hematological malignancies. Our present case is essentially the same as in the preceding two cases in that endocarditis occurred during the hematological remission. These clinical, observations may suggest that every leukemic patient suffering from aspergillosis is susceptible to the valvular complication after, rather than during, the period of severe myelosuppression, because platelets play an important role in the formation of thrombotic lesions. PMID- 3098031 TI - Reappraisal of high-dose desferrioxamine therapy. PMID- 3098032 TI - Reactivity of monoclonal antibodies LAU-A1 and anti-Y 29/55 in T and B cell malignancies of children: correlation with immunological markers and clinical data. AB - The monoclonal anti-pan-T cell antibody LAU-A1 stained neoplastic T cells arrested at different levels of maturation from all 21 children with T cell malignancies examined. Particularly in 7 patients with immature T cell neoplasia staining for LAU-A1 facilitated the recognition of a T cell origin of the malignant cells. Only 40% of these immature T cell malignancies were associated with an anterior mediastinal mass. A subdivision of T cell neoplasia into 4 differentiation-related subgroups did not permit to make predictions regarding the patients' survival. Despite the rather uniform clinical presentation the immunological phenotypes of tumor cells in 14 children with B cell non-Hodgkin's lymphoma (B NHL) were heterogeneous. Tumor cells lacked surface immunoglobulins (2 patients), expressed IgM only (7 patients), IgM and IgD (3 patients) or IgM, IgD and IgA (2 patients). Regardless of surface immunoglobulin expression anti-Y 29/55 stained practically all recognizable tumor cells of all B NHL examined. No correlation was found between the number of heavy-chain isotypes expressed on tumor cells and the survival of the patients. The only long-term survivors were 3 children transplanted with autologous bone marrow which had been purged in vitro with anti-Y 29/55 and complement. PMID- 3098033 TI - End-tidal CO2 monitoring during anesthesia. PMID- 3098034 TI - Pulmonary perfusion in HFV: a potential hazard? AB - Capnograms recorded during HFV do not indicate ETCO2 but the washout difference (WOD). A method by which the ETCO2 can be accurately measured during HFV using a special device and a low flow sidestream capnograph is described. The importance of continuous, instantaneous ETCO2 monitoring is stressed. Capnograms recorded by this method were found to exhibit regular, periodical falls in WOD as soon as the heart rate (HR) approached the ventilator rate (VR) or its second or third harmonic. Simultaneous rises in PAP, RVP and CVP were noted. Using an oscillator model and two frequencies representing the HR and VR, innumerable patterns could be produced resulting from the interference of one frequency with the other. Different combinations of frequencies produced, when expressed in terms related to alveolar capillary flow, zero or near-zero zones which varied in duration from extremely prolonged to minimal or entirely absent. Analysis of the capnographic phenomena previously observed, by means of the patterns produced by the oscillator model, enabled such disturbances to be interpreted and avoided, clinically, by adjustment of the relative HR/VR. The advantages of capnographic monitoring in the prevention of such sequelae during HFV is emphasised. PMID- 3098035 TI - Alfentanil infusion for abdominal surgery. AB - Twelve patients undergoing abdominal surgery were studied. Alfentanil was used as the sole anesthetic agent in these patients via a predetermined infusion regime. In 7 cases this was sufficient but in five cases the infusion had to be supplemented. Induction was with alfentanil 100 micrograms/kg over 2 minutes, then 10 micrograms/kg/min for 10 minutes followed by 2 micrograms/kg/min for 50 minutes. After one hour the infusion rate was varied between 1-3 micrograms/kg/min. Vecuronium 0.1 mg/kg with increments of 0.025-0.075 mg/kg was used for neuromuscular blockade in nine patients, the other three patients received identical doses of pancuronium. There was no statistically significant change in blood pressure and heart rate after induction or in response to intubation and both were well maintained throughout surgery. PMID- 3098037 TI - Effects of ethylhydroxydiphosphonate (EHDP) on heterotopic ossification. AB - The effect of EHDP medication was studied in 25 patients in whom heterotopic ossifications around the hip (19 cases) and elsewhere were resected. EHDP seemed to have a favorable effect on prevention of reossification and on function, particularly when ectopic ossifications were resected after total hip replacement. In all the patients, EHDP administration postponed mineralization of osteoid. PMID- 3098036 TI - Failure of thyrotropin releasing hormone to reverse fentanyl-flunitrazepam anesthesia in man. AB - The effect of thyrotropin releasing hormone (TRH) on modified neuroleptanesthesia with fentanyl-flunitrazepam was investigated in an open pilot study of 15 neurosurgical patients. Before and 15, 30, and 60 minutes after extubation and subsequent administration of 400 micrograms TRH, the following parameters were evaluated: PaO2, PaCO2, vigilance, and pain sensation. Although no TRH-related impairment of postoperative analgesia was observed, respiratory depression and impaired vigilance were not significantly reversed. These findings contradict a number of experimental studies using animal models which indicated that TRH, due to its centrally mediated ergotropic activity, antagonizes the narcotic effect of various CNS depressants and anesthetics. PMID- 3098038 TI - [Heterotopic ossification in hip arthroplasties]. PMID- 3098040 TI - Scanning electron microscopy of the sarcocysts of six species of Sarcocystis from reindeer (Rangifer tarandus tarandus). AB - Sarcocysts belonging to six species of Sarcocystis were isolated from the musculature of reindeer and examined by scanning electron microscopy (SEM) to reveal their surface morphology. Sarcocysts of S. grueneri had thin, strip-like surface processes, cysts of S. rangi had long hair-like processes, and cysts of S. tarandivulpes had short, knob-like processes interconnected by microfolds. Cysts of S. hardangeri had prominent, slanting linguiform processes, whereas the cysts of both S. tarandi and S. rangiferi had upright finger-like surface projections. The processes of S. rangiferi were thicker and longer than those of S. tarandi. SEM of the cysts of these species corroborated and supplemented previous descriptions of their surface morphology, which were based on transmission electron microscopy. PMID- 3098039 TI - Osteochondral fractures of the knee and the ankle joint. Clinical experiences using fibrin sealant. PMID- 3098041 TI - Effect of culture medium and carbon dioxide concentration on growth of anaerobic bacteria and medium pH. AB - Two Danish agars, Danish Blood Agar (D.B.A.) and Anaerobic Agar (A.A.), were evaluated for their ability to support growth of 47 clinically isolated anaerobic strains in 5 different CO2-concentrations ranging from 0-10% CO2. CO2 and the use of an enriched medium (A.A.) are essential for satisfactory recovery of anaerobes. No gain could be seen when raising the CO2-concentration above 5%. The surface pH of the agars was measured both on non-inoculated and inoculated plates at room temperature and anaerobic incubation in the 5 different CO2 concentrations at 37 degrees C. Temperature change from room temperature to 37 degrees C resulted in a pH decrease of 0.1 units. There was a CO2-mediated decrease in pH (approximately 0.05 units/pr. CO2%) on non-inoculated media. On inoculated plates there was a minor additional fall in pH, which increased with time of incubation, but first became significant when the plates were incubated for more than 24 h. The use of 5% CO2 and A.A. is recommended for antimicrobial susceptibility studies on solid media. PMID- 3098042 TI - Effect of fibroblast interferon and recombinant gamma interferon on zymosan induced nitroblue tetrazolium reduction in mouse peritoneal macrophages. AB - Mouse peritoneal macrophages (MPM) were cultivated with a fibroblast interferon (IFN) preparation or recombinant gamma-IFN (rIFN-alpha) for 1, 24 or 48 h. The zymosan-induced reduction of nitroblue tetrazolium (NBT) in these MPM was then measured. Fibroblast IFN enhanced the NBT reducing capacity of MPM when the incubation period was 1 h. When the incubation period was extended to 48 h, a suppressed NBT reduction by fibroblast IFN treated MPM was recorded. The influence of rIFN-alpha on MPM with regard to NBT reduction was minor. Only when the MPM were treated with a moderate dose of rIFN-alpha (10 U/ml) for 48 h was an enhanced NBT reduction recorded. PMID- 3098043 TI - Population analysis of susceptibility to ciprofloxacin and nalidixic acid in Staphylococcus, Pseudomonas aeruginosa, and Enterobacteriaceae. AB - Susceptibility to ciprofloxacin (Cfl) and nalidixic acid (Nal) was tested in vitro by means of the population analysis technique against six strains of Staphylococcus, one strain of Pseudomonas aeruginosa, and seven strains from five genera of Enterobacteriaceae. All strains of Staphylococcus were uniformly resistant to Nal as was the Pseudomonas aeruginosa strain, all bacteria being resistant to 250- less than 500 micrograms/ml. The Enterobacteriaceae were heterogeneous as regards susceptibility to Nal. With some strains minority populations of highly-resistant bacteria could be detected with frequencies of about 10(-6.3). The MIC for Cfl for the staphylococci varied between 0.25 and 0.50 microgram/ml. There were no differences in MIC of penicillinase-producing and penicillin-susceptible strains, either in Staphylococcus aureus or in Staphylococcus epidermidis. The MIC for Cfl in the enterobacteria varied between 0.004 and 0.03 microgram/ml. The MIC for Cfl in the Pseudomonas aeruginosa was 0.25 microgram/ml. MIC for Cfl increased in all strains when the parental strains were compared to bacteria selected from the plates with the highest concentration permitting growth, indicating heterogeneity against Cfl. But while the MIC of the selected enterobacteria were lower than one fourth of the level obtainable in serum, the MIC of the selected staphylococci and Pseudomonas aeruginosa were either exceeding the level obtainable in serum or were only a little lower than this level. While Cfl thus seems to be a promising antimicrobial agent in the treatment of infections caused by enterobacteria, the suitability for infections caused by staphylococci and Pseudomonas aeruginosa should be further explored. PMID- 3098044 TI - Non-invasive techniques used to monitor peripheral circulatory changes induced by nitroglycerin. AB - The antianginal effect of nitroglycerin is mainly mediated by its pronounced effects on peripheral vessels. These include an increased venous distensibility as well as a dilating effect on large arteries, a decreased arterial stiffness and an increased muscular and skin blood flow. These changes have been used to monitor and to assess the effects of various nitroglycerin preparations in numerous studies. The most frequently used techniques to demonstrate peripheral effects of nitroglycerin are summarized. PMID- 3098045 TI - Tolerance development during transdermal administration of nitroglycerin in angina pectoris. AB - Nitroglycerin delivered by transdermal patch technology has been used in angina pectoris patients as well as in heart failure. In angina pectoris patients the plasma concentrations are low over the 24 hours. Effects can be found especially during the first 12 hours after application of the drug even during steady state conditions. The effect of the drug wanes after 24 hours and some studies suggest reduced effect when the patches have been applied for seven to 14 days. The attenuated effects have been claimed to be due to tolerance. Tolerance is, however, never absolute and in other studies this phenomenon is not shown. Furthermore, rebound phenomena may develop when nitroglycerin therapy is withdrawn. The optimal doses and schemes for nitroglycerin administration thus remain to be clarified. PMID- 3098046 TI - Tolerance to organic nitroesters in experimental animals. An assessment of in vitro and in vivo investigations. AB - This paper will present a short survey of the literature dealing with nitrate tolerance in experimental animals. Tolerance towards organic nitroesters has been experimentally established in animal models both in vivo and in vitro. However the dose of drug used to provoke tolerance has invariably been very high, which makes it difficult to apply experiences from animal experiments to the clinical setting. Several different hypothesis has been put forward in order to explain the mechanism of tolerance. Today, most evidence seem to point towards an altered metabolism of cGMP as a possible cause of tolerance. Cyclic GMP is the second messenger suggested to mediate the vasodilatory effect of organic nitroesters. The proposed role of critical tissue sulfhydryl groups in mediating the smooth muscle relaxant effect of nitroglycerin (NTG) have made experiments concerning reversal and prevention of tolerance to center on the use of various sulfhydryl reactive compounds. The results of these experiments are as yet ambiguous. Several studies show the existence of cross tolerance between NTG and various other vasodilatory organic nitroesters. In contrast no cross tolerance between NTG and chemically unrelated vasodilator drugs has been observed. The endogenous vasodilators acetylcholine and atrial natriuretic factor are known to induce cGMP increases. In view of this, their effect on NTG-tolerant bovine mesenteric arteries was investigated. However no cross-tolerance appears to exist under in vitro conditions. PMID- 3098047 TI - The use of invasive techniques to study circulatory effects of nitrates. AB - The hemodynamic effects of NTG are easily studied with the use of invasive techniques. This article presents and discusses the most commonly used parameters obtained from cardiac catheterization and angiography to describe the effects of nitrates on the central circulation and the left ventricular function. PMID- 3098048 TI - Evaluation of effects of nitroglycerin therapy by echocardiography. AB - Echocardiography (Echo) is a convenient method in diagnosing and in quantification of cardiac abnormalities, although dependent on registration quality. M-mode and two-dimensional Echo give adequate information regarding heart dimensions and cavity volume but only indirect information of pressures. M mode Echo gives an ideal opportunity to study left ventricular wall motion as an expression of systolic and diastolic function. Both inter and intra patient comparisons will be possible to perform. Improved wall function after intake of nitroglycerin and other nitrate preparations, has been reported in Echo studies both in resting state and in induced acute myocardial ischemia during exercise in man or in acute coronary occlusion in dogs. PMID- 3098049 TI - Cardiovascular effects of nitroglycerin as evaluated by radioisotope methods. AB - Radioactive methods have successfully been used to elucidate the cardiovascular effects of nitroglycerin for decades. Xenon-clearance and the single probe technique were originally used to measure changes in myocardial flow caused by sublingual nitroglycerin. Later, similar studies were performed using the Anger camera permitting observations on regional myocardial flow. Microsphere techniques contributed to a better understanding of myocardial distribution of capillary flow. Modern methods in nuclear cardiology such as myocardial scintigraphy and gated blood pool scanning have shown their usefulness in demonstrating the cardiovascular effect of nitroglycerin on cardiac performance. The potential use of these non-invasive methods to study nitroglycerin effects is discussed. PMID- 3098050 TI - Nitroglycerin and arterial compliance. AB - The primary effect of nitrates on the circulatory system is a relaxation of capacitance vessels on the venous and arterial side, while dilatation of resistance vessels (arterioles) is a secondary phenomenon, or occurs only at higher doses. Relaxation of arteries may augment flow in conditions where these vessels offer an increased resistance due to e.g. spasm. Relaxation of capacitance arteries explains in part the lower systolic blood pressure after nitroglycerin. Improved "Windkessel" function may augment diastolic arterial pressure and thus improve coronary perfusion. Some methods for measuring arterial compliance are described. It is suggested that more simple measurements of arterial pulsations may be used for studying nitroglycerin tolerance. PMID- 3098052 TI - Metabolic effects of long-term arterialization of portal blood. AB - In nine splenectomized male dogs a splenic artery, -splenic vein shunt was made. Before splenectomy and 3, 6 and 18 months after arterialization of portal blood, different metabolic and endocrine parameters were estimated. Long-term arterialization of portal blood was followed by only insignificant increase of portal vein pressure but a significant drop of pCO2 and increase of pO2 in portal blood was recorded. Simultaneously, a significant decrease of the erythrocyte count, hematocrit value, serum cholesterol and uric acid levels, and a shortening of the T1/2 of insulin and glucagon were found. In contrast, long-term arterialization of portal blood was followed by a significant increase of serum triglycerides, alpha2-globulins, plasma renin activity, cortisol, gastrin and 25 hydroxyvitamin D, and by slight carbohydrate intolerance. No morphological abnormalities in the liver and kidney tissue were found. Data presented in this paper suggest usefulness of a splenic artery-splenic vein shunt in the treatment of some metabolic disorders and of the failing hepatocytes. PMID- 3098051 TI - Inhibition of lipid oxidation by serum and albumin. AB - The influence of serum and albumin on enzymatic and non-enzymatic lipid oxidation was investigated. Intensity of oxidation was measured as the amount of oxygen consumed by the sample and by quantitation of malonaldehyde formed during breakdown of lipid peroxides. Non-enzymatic lipid oxidation was stimulated by ascorbic acid or ferrous ions and enzymatic by NADPH-dependent oxidase, 15 lipoxygenase and 12-lipoxygenase. Albumin inhibits lipid oxidation only when pure fatty acid (arachidonic or linoleic) is the substrate for this oxidation. Serum was a stronger inhibitor than an equivalent amount of albumin and it also inhibited oxidation of a mixture of lipids from liver microsomes. It is concluded that serum contains two antioxidant factors: albumin which binds fatty acids and probably another factor which is a true antioxidant. PMID- 3098053 TI - Histochemical localization of carbonic anhydrase in the pig's exocrine pancreas. AB - Carbonic anhydrase is essential for the pancreatic secretion of NaHCO3. To localize the distribution of carbonic anhydrase in the exocrine gland and, hence, identify the potential cellular source of secreted NaHCO3, histochemical staining of carbonic anhydrase was carried out on pancreatic biopsies obtained from six pigs at both supramaximal intravenous secretin stimulation and at secretory rest. Tissue staining, using Hansson's technique, revealed a strong staining both in membranes and cytoplasm in the duct cells and a weaker cytoplasmic staining in the acinar cells. Staining reaction was abolished by 10(-5) mol l-1 acetazolamide. Duct cells, accordingly, seem to be responsible for NaHCO3 secretion, while acinar cells appear unlikely to contribute substantially to NaHCO3 secretion. PMID- 3098054 TI - [Studies of pyrazine derivatives. XX. Synthesis and tuberculostatic activity of 3 pyrazinol-1,2,4-oxadiazole derivatives]. PMID- 3098055 TI - Evaluation of community services. AB - Implementation and expansion of community-based psychiatric services was followed by a wide range of positive and negative effects. Differences seem due to scale and speed of implementation, to proper coordination with closing down mental hospitals, but also to differences in goals and expectations as well as methods applied to reach them. An analysis of empirical evaluation studies reveals a series of conceptual and methodological difficulties. Operational research has been limited so far by the scarcity of controlled studies and especially of multicenter coordinated research. The same is true for evaluation using external criteria, for instance evaluation of utilization data, of unintentional side effects etc. The preventive effects of community psychiatry are practically not evaluated on the levels of primary and secondary prevention. On the other hand, important studies have been made on the transfer of care from mental hospitals to alternative care, especially in nursing and boarding homes; its results reveal an important deficit of adequate care for those who have been deinstitutionalized but without profiting from the community mental health movement. The conclusions concern the reorientation of goals for community psychiatry, the priorities of care in times of limited resources, and the specifications for evaluative research in the future. PMID- 3098056 TI - Norrie-Warburg syndrome. PMID- 3098057 TI - Neuronal and glial pathologies: morphology and physiology of human and monkey epileptic foci. PMID- 3098059 TI - The hyperexcited brain: glutamic acid release and failure of inhibition. PMID- 3098058 TI - Subcortical projections from the amygdaloid complex. PMID- 3098060 TI - Organization and expression of gonadotropin genes. AB - We have examined the question of how hormones regulate the biosynthesis of gonadotropins. In particular we have studied the effects of gonadal sex steroid hormones on the regulation of LH subunit gene expression to determine whether they may occur at the pre-translational level. Success in the molecular cloning of cDNAs in genes encoding the subunits of LH has allowed such studies. It is now known that the subunit genes are located in separate genes on separate chromosomes in man and mouse. These genes must be coordinately expressed in a tissue-specific fashion in gonadotropes to yield subunit mRNAs which are ultimately translated to form the protein backbones of the subunits. It is clear that the gonadal sex steroid hormones in both castration and castration replacement experimental paradigms negatively regulate the subunit mRNAs in vivo in a rapid and effective manner. Also, it is interesting to note that alpha subunit RNA is regulated to a lesser extent than the LH beta. This observation is reminiscent of those previously observed in the studies of the biosynthesis of TSH in which the subunit mRNA is less well controlled than the TSH beta mRNA. These studies were performed initially using thyrotropic tumor which lacked confounding gonadotropes. However, studies have also been performed in the pituitary gland of the hypothyroid mouse with similar results. Hence, it appears that the alpha subunit gene is also under regulation by hormones but to a lesser extent than the LH beta. These findings provide hope that future studies will allow us to understand further the molecular mechanisms involved in the regulation of these genes by various hormonal influences. PMID- 3098062 TI - [Clinical experience in surgical implantation]. PMID- 3098061 TI - Arachidonic acid metabolism by the 5-lipoxygenase pathway, and the effects of alternative dietary fatty acids. PMID- 3098063 TI - [Treatment of prostatic cancer with an LH-RH analog]. AB - LH-RH analog (Buserelin) was administered in 10 cases of untreated prostatic cancer in our hospitals. All 10 cases had stage D2 disease. Five cases were of moderately differentiated carcinoma and 5 cases were of poorly differentiated carcinoma. The levels of luteinizing hormone and follicle stimulating hormone in blood plasma tended in decrease four weeks after treatment except for one case. The levels of testosterone in blood plasma reached the castrated level four weeks after administration except for the above one case. In adjacent effect by National Prostatic Cancer Project Criteria, the LH-RH proved to be effective in 6 of the 10 cases. The flush of face appeared in two cases, but it disappeared spontaneously. One case had a slight temporal macrohematuria one week after treatment. PMID- 3098064 TI - Cranial MR in spinal cord MS: diagnosing patients with isolated spinal cord symptoms. AB - MR brain scans, spinal fluid electrophoresis, and evoked responses were obtained in 10 adult patients with isolated spinal cord symptoms diagnosed as possible multiple sclerosis (MS) according to the McAlpine criteria. Typical lesions of MS were found on T2-weighted MR images in six patients. Spinal fluid abnormalities were found in four. Visual-evoked responses or brainstem auditory-evoked responses were abnormal in three. MR in conjunction with spinal fluid analysis supported the diagnosis of MS in eight of 10 patients. Evoked responses appeared less sensitive than MR in identifying subclinical lesions in this population. PMID- 3098066 TI - MR imaging in progressive multifocal leukoencephalopathy. AB - The MR imaging appearance of progressive multifocal leukoencephalopathy is described in four cases that were confirmed by brain biopsy. Characteristic aspects are long T1 and long T2 lesions limited to white matter. At first the lesions are round or oval, then confluent and large. There is no mass effect. The involvement is most often asymmetric and distant from the periventricular region. The differential diagnosis includes other diseases affecting white matter: demyelination, infarction, infection, and tumors. PMID- 3098065 TI - Time-dependent changes in image contrast in brain tumors after gadolinium-DTPA. AB - Time-dependent changes in the contrast enhancement of tumor tissue, tumor necrosis, perifocal edema, and normal brain tissue after IV injection of 0.1 mmol gadolinium-DTPA/kg body weight were studied with spin-echo technique (SE 800/35) in 15 patients with intracranial tumors. Using a region of interest technique, we determined the signal-intensity values of these tissues before and at fixed times up to 68.5 min after administration of the contrast agent. In tumor tissue, the 8.5 min postinjection (p.i.) scan showed a significant increase in signal intensity. The signal intensity of the tumor tissue remained significantly higher than precontrast levels throughout the entire period of observation, decreasing only slightly toward the end of the examination (48.5 and 68.5 min p.i.). Central tumor necrosis exhibited a delayed uptake of the contrast agent, with a maximum signal intensity between 48.5 and 68.5 min p.i. In perifocal edema and normal brain tissue, slight increases in signal intensity after injection of gadolinium DTPA were measured (statistically significant in the case of edema). This effect, however, was not visually detectable. The present study shows that after one injection, scans with excellent tumor visualization can be obtained between 8.5 and 38.5 min p.i. and with diagnostically valid enhancement at least up to 68.5 min p.i. PMID- 3098067 TI - Cardiac-gated local coil MR imaging of the carotid neck bifurcation. PMID- 3098068 TI - MR and CT investigation of cerebrovascular disease in sickle cell patients. AB - Stroke is a common complication of sickle cell disease. Using MR and CT, we studied 10 patients with sickle cell disease and a history of stroke and compared these findings with those of 10 sickle cell patients without stroke. The purpose was to determine if MR could visualize the large vessel vasculopathy previously seen on angiography and to estimate the incidence of asymptomatic abnormalities in the nonstroke group. MR consistently demonstrated the major intracranial arteries and showed three cases with occlusion and three with stenosis of either the internal carotid or middle cerebral arteries. Infarctions were better delineated on MR but were also seen on CT. Seven cases with and two without stroke had high-signal white matter lesions on MR. Further research using cranial MR to develop noninvasive means of identifying sickle cell patients at risk for stroke is warranted. PMID- 3098069 TI - Percutaneous laser catheter recanalization of carotid arteries in seven cadavers and one patient. PMID- 3098070 TI - A prospective comparison of duplex sonography vs angiography of the vertebral arteries. AB - A prospective blind comparison was completed between duplex sonography and angiography of the vertebral arteries. Thirty-two vertebral arteries were studied for direction of flow, degree of origin plaque or stenosis, Doppler characteristics, and vessel size. The vertebral arteries were reliably identified by imaging their course from the subclavian artery into the transverse foramina and by identifying a Doppler signal similar in waveform to the internal carotid artery. With Doppler, a 90% accuracy was obtained for direction of blood flow. Nonvisualization of origins was primarily due to vessel depth and/or tortuosity. In 12 vessel origins that were well seen with both techniques, angiography and sonography agreed in two-thirds of the cases. In four cases, origin plaque was underestimated with duplex imaging. Interestingly, no Doppler frequency or velocity elevation was identified distal to significant stenoses. One false positive diagnosis of occlusion occurred with sonography, in which a 99% origin stenosis resulted in no detectable Doppler signal. By comparing sonography with angiography, sonography was shown to be 80% accurate in determining vertebral artery size. Our preliminary results indicate that duplex scanning is a reasonably accurate screening technique for size, patency, and direction of blood flow in the vertebral arteries. Duplex evaluation of the vertebral artery origin was limited by vessel depth, tortuosity, and calcifications. PMID- 3098071 TI - Ventricular septa in the neonatal age group: diagnosis and considerations of etiology. AB - Twenty-four patients with ventricular septa are discussed. Seventeen patients had septa acquired during the neonatal period and seven exhibited septations at birth (cogenital septa). Among the acquired septa, there were true intraventricular septa and septa that originated outside the ventricles but later became part of the ventricular system (pseudosepta). Pseudosepta originate in necrotic, cavitating periventricular white matter that, in temporal sequence, becomes ventricularized. Serial use of cranial sonography provided important information about the pathologic mechanisms that govern the development of septa. Intraventricular hemorrhage and infection are the major causes of true intraventricular septa, while periventricular leukomalacia serves as primary cause of pseudosepta. Sonography is the diagnostic method of choice. Septa are associated with a high incidence (62%) of shunt failure. PMID- 3098072 TI - Focal necrosis of the white matter (periventricular leukomalacia): sonographic, pathologic, and electroencephalographic features. AB - Eleven preterm infants (gestational ages 27-35 weeks) with echogenic paraventricular white matter identified shortly after birth were studied with serial echoencephalograms to fully delineate the sonographic findings characterizing the pathologic stages of white-matter necrosis. Echoencephalograms were compared with autopsy findings and CT scans. Cerebral function was assessed by electroencephalograms and later by neurodevelopmental evaluations. Echogenic areas were observed in the paraventricular white matter in the acute stage. Microscopically, the echogenic white matter consisted of vascular congestion and petechial hemorrhages, but not always with foci of necrosis. Anechoic areas, which characterized the chronic stage, corresponded to cavitary lesions, and these generally appeared within 2 weeks of birth. However, six infants had anechoic lesions by day 4, suggesting that the onset of white-matter damage was antenatal. CT showed mildly decreased attenuation when paraventricular echogenic areas alone or in association with small anechoic areas were observed. Markedly decreased attenuation on CT scans corresponded to large anechoic areas. Resolution of the sonographic and CT findings did not indicate normalization of the white matter since all surviving infants were neurologically abnormal at 1 year. Electroencephalograms with central (rolandic) positive sharp waves were associated with echogenic white matter alone or with evolving anechoic areas. All patients with positive sharp waves on electroencephalograms had large anechoic areas in later studies. Early and serial echoencephalograms are necessary to evaluate white-matter necrosis in preterm infants. When echogenic white matter is identified, electroencephalography can suggest the presence of white-matter necrosis. PMID- 3098073 TI - Pineal cysts: MR imaging. AB - MR brain scans of 672 consecutive patients were examined prospectively to determine the incidence of high-signal pineal glands on T2-weighted images. The scans were obtained on either a 0.15-T or 0.5-T unit. This finding was present in 29 patients, none of whom had hydrocephalus or symptoms of a pineal mass. A CT scan was available in 17 of these cases and none of these demonstrated a solid pineal mass. Because of the frequency of this observation (4.3%) and the absence of associated findings, it was concluded that benign pineal cysts are the most likely explanation for this high signal. It is important for the radiologist to consider benign cysts in the differential diagnosis of a bright pineal gland on T2-weighted MR images. PMID- 3098074 TI - Demonstration of a symptomatic intraventricular cyst using direct intraventricular metrizamide instillation. PMID- 3098075 TI - Cervicomedullary hematoma: diagnosis by MR. PMID- 3098076 TI - Posterior fossa chronic subdural hematoma in the neonate. PMID- 3098077 TI - MR imaging, CT scan, and clinical examination in multiple sclerosis. PMID- 3098078 TI - Importance of sagittally reformatted images in CT evaluation of spondylolisthesis. PMID- 3098079 TI - Anterior cervical meningoceles in neurofibromatosis. PMID- 3098080 TI - The behavior of Pantopaque on MR: in vivo and in vitro analysis. AB - MR imaging is considered by many to be the procedure of choice in imaging the spinal cord; yet we encountered an important pitfall of this procedure in the form of a patient with retained intraspinal Pantopaque. The results of this case are presented as well as those obtained in another patient with retained Pantopaque. Also described is the behavior of this contrast material when using in vitro imaging data obtained from a CSF/Pantopaque phantom. When T1-weighted imaging sequences are used, Pantopaque gives a high signal and CSF gives a low signal. With long repetition time, (e.g., 4000 ms), the CSF signal is high and the Pantopaque signal is not. With repetition time around 1000 to 2000, both may be isointense. The implications of these findings are discussed. PMID- 3098081 TI - Transdermal nitroglycerin. PMID- 3098082 TI - Are there unnecessary delays in the development of new cardiac drugs in the United States? PMID- 3098083 TI - Net protein anabolism with hypocaloric parenteral nutrition in obese stressed patients. AB - Thirteen obese patients requiring parenteral nutrition for postoperative complications were studied prospectively to evaluate the efficacy of hypocaloric, high-protein parenteral feeding. Nonprotein caloric intake averaged 881 kcal/d or 51.5% of the patients' measured resting energy expenditure. Protein intake averaged 2.13 +/- 0.59 g/kg IBW. Serum albumin and TIBC increased significantly (2.8 +/- 0.5 g/dL to 3.2 +/- 0.4 g/dL, p less than 0.01, and 196 +/- 39 micrograms/dL to 248 +/- 49 micrograms/dL, p less than 0.05, respectively), and subjects lost weight (120.0 +/- 60.0 kg to 109.7 +/- 32.5 kg, p less than 0.05). Nitrogen balance studies in eight subjects suggested nitrogen equilibrium or positive balance can be achieved (+2.4 +/- 1.9 g/d). All patients exhibited complete tissue healing of wounds and abscess cavities and closure of fistulae. In obese, protein-depleted surgical patients net protein anabolism and clinical efficacy can be achieved with hypocaloric, high-protein feeding. Abundant endogenous fat stores provide obligatory energy. PMID- 3098084 TI - Nutritional assessment and skeletal muscle function. AB - The validity of skeletal muscle function as a functional measure of nutritional state was determined by stimulating the ulnar nerve at the wrist and measuring the force of isometric contractions of the adductor pollicis muscle. Nutritional state was evaluated by measuring body composition, by multiple-isotope dilution, in 21 malnourished and 44 normally nourished patients. No significant correlation between body composition and muscle function was found. In eight normally nourished volunteers, muscle function was determined before, after 24 and 48 h of complete starvation, and 6, 24, and 48 h following resumption of normal diet. Muscle function became abnormal after 24 h of starvation and deteriorated further after 48 h. Six hours following a single normal meal, muscle function returned to normal. Experimental data indicate that the response of the adductor pollicis muscle to ulnar nerve stimulation is not an accurate measure of nutritional state. PMID- 3098085 TI - Vitamin B-6 nutriture and plasma diamine oxidase activity in pregnant Hispanic teenagers. AB - Vitamin B-6 status was assessed by measuring erythrocyte glutamic-pyruvic transaminase (EGPT) indices in 122 pregnant Hispanic teenagers. Seventeen percent were vitamin B-6 deficient (EGPT indices greater than 1.25) at the initial interview (first or second trimester). A daily supplement of 5 mg vitamin B-6, beginning at initial interview, did not reduce prevalence of vitamin B-6 deficiency at final interview (third trimester). No association was found between EGPT indices greater than 1.25 and the outcome of pregnancy. The activity of diamine oxidase (DAO), a vitamin B-6-dependent enzyme produced by the placental decidua, was measured in maternal plasma. At initial and final interviews, plasma DAO activity was increased by in vitro addition of pyridoxal-5'-phosphate. The activity in early pregnancy was positively associated with dietary vitamin B-6 intake and was lower in teenagers with EGPT indices greater than 1.25 at the final interview. Findings suggest that plasma-DAO activity is influenced by vitamin B-6 status. PMID- 3098086 TI - Physical aspects of radiation treatment. Some past and present developments with implications for the future. AB - Some aspects of the development and initial use of high energy photons and electrons are discussed, including the initial roles of Kerst and Quastler. Analytical developments in brachytherapy are also described. Relative to orthovoltages, the availability of high energy photons and electrons have provided the opportunity for concentration of ionizing energy anywhere in the body. Computer methods became necessary to handle the number of computations required in treatment planning, and the development of computerized treatment planning over the past 3 decades is sketched, with emphasis on current multidimensional planning. Both anatomical detail and dose distributions are now displayed in any arbitrary plane with radiation beams incident at any angle. The physical advantages of high energy photons are assessed, as well as increasing limitations with increasing energy, leading to determination of optimum photon energy ranges relative to lesion sites. A recent advance in the analysis of interstitial implants is discussed, which provides a basis for quantitative evaluation of implant systems and their application to specific cases. Further anticipated developments of these current advances are summarized. PMID- 3098087 TI - Facial morphology and obstructive sleep apnea. AB - In a sample of 25 adult male subjects with moderate to severe obstructive sleep apnea, the interaction among craniofacial, airway, tongue, and hyoid variables was quantified by means of a canonical correlation analysis. One lateral cephalometric radiograph with the teeth in occlusion was obtained for each subject together with overnight polysomnographic measurements before the initiation of therapy. A principal component analysis reduced the data base and one significant canonical correlation (r1 = 0.994) was identified for the 22 variables. Sleep apnea subjects showed a posteriorly positioned maxilla and mandible, a steep occlusal plane, overerupted maxillary and mandibular teeth, proclined incisors, a steep mandibular plane, a large gonial angle, high upper and lower facial heights, and an anterior open bite in association with a long tongue and a posteriorly placed pharyngeal wall. A multivariate statistical analysis extracted clinically significant associations among craniofacial, tongue, and airway variables. Subjects with sleep apnea demonstrated several alterations in craniofacial form that may reduce the upper airway dimensions and subsequently impair upper airway stability. PMID- 3098088 TI - The future of pediatrics. PMID- 3098089 TI - Surreptitious insulin administration. PMID- 3098090 TI - Immunohistochemical studies on structural changes of the hepatic lobules in chronic liver diseases. AB - Liver biopsy specimens were examined immunohistochemically to clarify structural changes of the hepatic lobules in chronic liver diseases. In normal liver carbohydrate antigen 19-9 was located in the biliary ductular epithelium, whereas factor VIII-related antigen was observed in the endothelium of portal veins, hepatic arteries, and central veins. This antigen was not detected in the sinusoidal endothelium. In contrasts, monoclonal antibody OKM5 was reactive with the sinusoidal endothelium but was unreactive with the endothelium of the portal blood vessels or central veins. In chronic active hepatitis and liver cirrhosis, both carbohydrate antigen 19-9 positive biliary ductular cells and factor VIII related antigen positive endothelial cells were not only observed in the enlarged portal area but also extended into the parenchyma. They were occasionally accompanied by fibers. These findings suggest that fibrosis, ductular epithelial, and blood vascular proliferation in the portal space and their invasion into the parenchyma might gradually cause structural changes of the hepatic lobules in chronic liver disease. PMID- 3098091 TI - The effect of underreporting on the apparent incidence and epidemiology of acute viral hepatitis. AB - To determine if passively reported cases of acute viral hepatitis are representative of the affected population, an active surveillance system was set up that identified all persons in Pierce County, Washington, who had been diagnosed by a physician as having acute viral hepatitis in the period March 1 through August 31, 1984. In this county, this was part of an ongoing epidemiologic study of viral hepatitis that had previously included some stimulation of reporting. The active surveillance system covered all primary sources of medical care, including all private physicians who were most likely to see persons with hepatitis. Secondary sources, those that did not provide direct medical care but might be aware of new cases, were also surveyed. The results of active surveillance showed that passive reporting was about 65% complete in Pierce County. No change occurred in the number of hepatitis A cases reported, but hepatitis B cases increased by 50%, and non-A, non-B hepatitis cases increased by 138%. Most of the increase was a result of enhanced reporting from private physicians. The two risk groups most affected by underreporting were homosexual men with hepatitis B and blood transfusion recipients with non-A, non B hepatitis. During active surveillance, the proportion of persons with hepatitis B who reported homosexual activity was 52% compared with 20% from passive surveillance. Transfusion recipients represented 24% of the non-A, non-B hepatitis reported from active surveillance compared with 9% reported from passive surveillance. Although Pierce County may not be representative of all counties in the United States, persons responsible for public health prevention programs should recognize that data acquired through passive surveillance may not accurately reflect the magnitude of the risk for specific populations or the amount of disease that can be prevented. PMID- 3098092 TI - Hepatitis B vaccination of 113 hemophiliacs: lower antibody response in anti LAV/HTLV-III-positive patients. AB - One-hundred thirteen adults and children with hemophilia or other congenital bleeding disorders were vaccinated against the hepatitis B virus. Each patient was given three subcutaneous injections of the vaccine at monthly intervals and then a fourth booster dose 14 months after the first. The vaccine was highly immunogenic, since 111 of 113 patients (98%) produced anti-HBs (10 mIU/ml or more). After the first three vaccine doses and after the booster dose, ten anti LAV/HTLV-III-positive hemophiliacs produced anti-HBs but had a lower average titer than anti-LAV/HTLV-III-negative hemophiliacs. Of the 23 patients treated with concentrates in the 15 month postvaccination period only, none acquired HBV infection. Of the 50 patients treated with concentrates also in the 6 month prevaccination period, one developed hepatitis B. In summary, the vaccine was highly immunogenic in both children and adults with hemophilia; anti-LAV/HTLV-III positive patients responded to the vaccine, but the average anti-HBs response was lower; no case of hepatitis B occurred in patients treated with concentrates only in the postvaccination period. PMID- 3098093 TI - Pure red cell aplasia: response to therapy with anti-thymocyte globulin. AB - Pure red cell aplasia (PRCA) results from the failure of erythrocyte differentiation and may respond to immunosuppressive therapies. We have treated nine patients with PRCA refractory to steroids and/or cyclophosphamide with anti thymocyte globulin (ATG). Six patients had normal numbers of erythroid bursts (from erythroid burst-forming units) or erythroid colonies (from erythroid colony forming units) detectable in vitro, and all responded to therapy with ATG. In vitro studies suggested T-cell inhibition of erythropoiesis in four of these six patients and humorally mediated erythroid suppression in one. In three individuals, virtually no erythroid progenitors were detected in marrow culture. None of these patients responded to ATG. Myelofibrosis, 5q- chromosomal abnormality, or the subsequent development of thrombocytopenia in these individuals suggested that PRCA resulted from an intrinsic stem cell disorder. Our studies demonstrate that ATG is effective therapy for PRCA, and it may be especially useful in children or other patients in whom alkylating agents are not appropriate. We also confirm that erythroid growth in marrow culture predicts those patients who will respond to ATG or other immunosuppressive therapies. PMID- 3098094 TI - Efficacy of danazol in pure red cell aplasia. AB - Twenty-one unselected patients with refractory chronic anemias of various etiologies were treated with danazol, a synthetic attenuated androgen. All had previously failed treatment with hematinics, androgens, corticosteroids, high dose intravenous immunoglobulin, antithymocyte globulin, cytotoxic immunosuppressive agents, and/or plasmapheresis. Three patients with pure red cell aplasia and one with aplastic anemia responded. No responses were observed in 11 patients with myelodysplastic syndromes, two patients with myelofibrosis, and two with paroxysmal nocturnal hemoglobinuria. Remission in pure red cell aplasia was maintained with danazol alone in one patient and required combined low-dose prednisone in two. Objective responses occurred in 2 to 3 weeks and therapy generally was well tolerated. To date, one patient with pure red cell aplasia remains in complete remission at 9 months on low-dose danazol alone. We conclude that danazol alone or combined with prednisone may induce and maintain remission in severe refractory pure red cell aplasia and possibly other chronic cytopenias characterized by immunologic marrow suppression. Further trials of danazol in treating these disorders are indicated. PMID- 3098095 TI - Lead nephropathy. AB - In the past, lead poisoning was recognized when classical symptoms of acute intoxication were present and the blood lead was elevated. The EDTA test is presently the most reliable method for detecting excessive lead stores. We used the EDTA lead-mobilization test to demonstrate excessive past lead absorption as a cause of renal disease in lead workers and in both gouty and hypertensive patients with renal failure. These studies show that lead nephropathy occurs in the absence of acute intoxication and that occult poisoning often goes unrecognized because of inappropriate diagnostic criteria. PMID- 3098097 TI - Short-term mortality and cancer incidence in capacitor manufacturing workers exposed to polychlorinated biphenyls (PCBs). AB - A cohort study of 142 male Swedish capacitor manufacturing workers was performed. PCB had been used as a dielectricum in power capacitors between 1960 and 1978. Mortality was investigated for the period 1965 to 1982 and cancer incidence from 1965 to 1980. Twenty-one deaths and seven cancers were observed, which was in agreement with the anticipated numbers calculated from national statistics. One person had developed two rare tumors, a slow growing mesenchymal tumor (desmoid) and a malignant lymphoma. The results cannot rule out the possibility of a carcinogenic risk from PCB exposure because of the small size of the cohort and relatively brief follow-up period, but they do not indicate any excess mortality or cancer incidence in this factory so far. PMID- 3098096 TI - Evidence that autoimmunity in man is a Mendelian dominant trait. AB - Family studies of autoimmune diseases are consistent with multifactorial etiology. However, familial occurrence of the autoimmune trait as defined by the presence of autoimmune disease and/or high titer autoantibody supports the hypothesis that autoimmunity is inherited as an autosomal dominant trait. Based on genetic analysis of 18 autoimmune kindreds, the population frequency of this primary autoimmune gene is approximately .10 with penetrance estimates of 92% in females and 49% in males. The estimated high penetrance of the autoimmune gene in females suggests that the interacting genetic and/or environmental factors must be numerous or ubiquitous. Sex, age, and specific major histocompatibility complex (MHC) antigens are among the genetic and physiological factors known to influence autoimmunity. A genetic model is proposed that takes these factors into account. Inherent in the hypothesis of a primary autoimmune gene is that it is epistatic to other, secondary, genes that influence the autoimmune phenotype. The genetic model further postulates that the secondary genes, including those of the MHC, confer specificity to the phenotype. The effects of the secondary genes can be modulated by gonadal steroids and, over time, may be abrogated by environmental challenges, such as viral infections. PMID- 3098098 TI - Recent developments in organizing and financing health-care services. AB - Recent developments in the organization and financing of health-care services are described. All recent developments reflect an effort by both private and public payers to restrict use of health-care services, as well as to control price. Private use-review programs, such as second-surgical-opinion services and case management services, are increasingly being used. The number of hospital admissions and length of patient stay continue to decline, but, because of increasing complexity of care, the cost of pharmaceutical services has not decreased proportionately. Points relating to health-care financing in the federal reconciliation budget effective May 1, 1986, are reviewed, as are other new federal regulations affecting the structure of services and terms of reimbursement under the Medicare and Medicaid programs. For Medicare, these include new scope objectives for professional review organizations, decreased return-on-equity payments to for-profit hospitals for outpatient services and to skilled nursing facilities, and elimination of waiver-of-liability presumptions for hospitals. Also, physicians must now identify specific services provided during each inpatient hospital visit. Most developments related to home health care services pertain to limiting the cost of durable medical equipment. Alternative types of health care based on capitation funding, such as health maintenance organizations, competitive medical plans, and preferred provider organizations, will continue to grow in both the public and private sectors, and the use of private use-review programs for controlling costs is expected to accelerate in the next year. PMID- 3098099 TI - Causes of windowing-induced dysmorphogenesis (neural tube defects and early amnion deficit spectrum) in chicken embryos. AB - Previous reports suggest that windowing the shells of chicken eggs during the first day of incubation frequently results in dysmorphogenesis of the central nervous system. We report here data that further delineate the neural tube defects associated with this animal model. In addition, we describe another birth defect syndrome associated with windowing: the early amnion deficit spectrum (EADS). Several components of the egg are altered structurally by windowing: the shell, outer and inner shell membranes, yolk, and air space at the blunt end of the egg. A new air space is formed over the embryo as the original one at the blunt end is obliterated. A series of studies (pH, oxygen and carbon dioxide tensions, relative humidity, temperature, and deformation of the yolk documented with magnetic resonance imaging) examining individual steps of the windowing procedure and additional techniques that stimulate windowing suggest that mechanical stress causes isolated neural tube defects and dehydration causes amnion defects. These amnion defects are associated with other embryonic abnormalities suggestive of deformations consistent with EADS. PMID- 3098100 TI - Pulmonary hypertension and interstitial fibrosis in von Recklinghausen neurofibromatosis. AB - Neurofibromatosis von Recklinghausen (NFvR) has been reported to be associated with diffuse interstitial pulmonary fibrosis. We describe a patient with NFvR presenting in middle age with dyspnea and cyanosis. Chest radiographs showed right ventricular enlargement, dilated proximal pulmonary arteries, and bilaterally increased interstitial markings. Cardiac catheterization showed moderately severe pulmonary hypertension and no evidence of congenital heart defect. The interstitial fibrosis associated with NFvR can result in symptomatic pulmonary hypertension. PMID- 3098101 TI - Congenital lid ptosis associated with neurofibromatosis. PMID- 3098102 TI - Human chorionic gonadotropin reduces aromatizable androgens and aromatase activity in women stimulated by clomiphene citrate and human menopausal gonadotropin. AB - Periovulatory steroidal dynamics in women undergoing ovulation induction with clomiphene citrate and human menopausal gonadotropin were studied in 31 women with tubal blockage. Serum estradiol levels were significantly reduced 36 hours after human chorionic gonadotropin administration (from 1792 +/- 162 to 926 +/- 132 pg/ml, p less than 0.001). Peripheral levels of testosterone and androstenedione did not change during this periovulatory time. Progesterone and 17 alpha-hydroxyprogesterone, as anticipated, significantly increased with an early rise noted within the first 8 hours of human chorionic gonadotropin administration (p less than 0.001). A significant reduction of the ratios of the steroidal pairs 17 alpha-hydroxyprogesterone-progesterone (17 alpha-hydroxylase) and androstenedione-17 alpha-hydroxyprogesterone (17,20-desmolase) was observed after human chorionic gonadotropin injection (p less than 0.001). Aromatase activity appeared to be inhibited because of a significant reduction in the estradiol/testosterone ratio 34 to 36 hours after human chorionic gonadotropin administration. Thus human chorionic gonadotropin, which triggers ovulation in women treated by clomiphene citrate-human menopausal gonadotropin, appears to partially reduce aromatizable substrate as well as inhibit aromatase activity. PMID- 3098103 TI - Effects of thyrotropin-releasing hormone in the fetal lamb. AB - Thyrotropin-releasing hormone causes neurobehavioral arousal and stimulates breathing in adult, newborn, and preterm experimental animals. Its effects on behavioral state, breathing, blood pressure, and heart rate were studied in the chronically instrumented late term fetal lamb. Fetal intravenous administration of thyrotropin-releasing hormone resulted in behavioral arousal with electrocortical desynchronization, increased body and eye movements, rapid and deep breathing movements, and a transient bradycardia followed by prolonged tachycardia, associated with an increase in both systolic and diastolic blood pressure. The effects were similar following intracisternal administration of thyrotropin-releasing hormone. The effects of thyrotropin-releasing hormone on behavior, but not breathing, was abolished in the presence of muscarinic blockade. Thyrotropin-releasing hormone may play a role in the modulation of central regulation of cardiovascular, respiratory, and behavioral activity in the fetus. PMID- 3098105 TI - Acute modulation of the hypothalamic-pituitary axis by intravenous testosterone in normal women. AB - Intravenous testosterone was infused for 6 hours in 23 ovulatory women, divided into five groups according to dose, to assess the effects of testosterone on gonadotropin secretion. Serum testosterone increased from 0.24 +/- 0.08 to steady state levels of 1.63 +/- 0.18 ng/ml in the lowest-dose group (1) and to 42.1 +/- 3.3 ng/ml in the highest-dose group (4). In another group (5), patients were pretreated with testolactone, which prevented the estradiol rise associated with testosterone infusion. All groups except group 1 exhibited significant reductions in the delta maximum responses of luteinizing hormone to gonadotropin-releasing hormone during testosterone infusion compared with pretreatment levels (p less than 0.01). This was also evident for the testolactone group (5). There were no observed changes in serum follicle-stimulating hormone. Luteinizing hormone pulse frequency was decreased (p less than 0.05) with testosterone concentrations of 27.2 +/- 0.77 and 42.1 +/- 3.3 ng/ml (groups 3 and 4), but only in the highest group (4) was there a decrease in pulse amplitude (p less than 0.05). No luteinizing hormone pulse changes were observed with lower concentrations of testosterone. Plasma immunoreactive gonadotropin-releasing hormone levels remained undetectable or low in some of the groups sampled. These data suggest that short-term infusions of testosterone inhibit hypothalamic-pituitary function of normal women when high doses are used, and this effect may be independent of aromatization to estrogen. PMID- 3098104 TI - Porcine follicular fluid protein(s) inhibit rat ovary granulosa cell steroidogenesis. AB - We examined the effect of an isolated fraction of follicular fluid, termed follicle regulatory protein, on the production of estrogen, progesterone, and 20 alpha-dihydroprogesterone by cultured rat ovarian granulosa cells. We found a stepwise decrease in estrogen production with an increasing concentration of follicle regulatory protein (9 to 300 micrograms/ml) when the cells were stimulated by 6.25 ng/ml of ovine follicle-stimulating hormone, but the addition of a saturating dose of ovine follicle-stimulating hormone (50 ng/ml) prevented the inhibitory effect of follicle regulatory protein on estrogen production. Follicle regulatory protein inhibited progesterone production at both low and saturating levels of ovine follicle-stimulating hormone. We examined whether cholesterol substrate in the form of high-density lipoprotein or low-density lipoprotein could overcome the follicle regulatory protein inhibition of progesterone and 20 alpha-dihydroprogesterone production stimulated by follicle stimulating hormone. At all concentrations of high-density and low-density lipoprotein, 75 micrograms/ml of follicle regulatory protein inhibited progesterone production by 80% to 90%. In the case of 20 alpha dihydroprogesterone, the presence of high-density and low-density lipoprotein accentuated the inhibitory effect of follicle regulatory protein. These results demonstrate that the effects of follicle regulatory protein on ovarian steroidogenesis depend on: the concentration of gonadotropin, the concentration of follicle regulatory protein, and the availability of cholesterol substrate. PMID- 3098106 TI - The effect of fetal urine on arachidonic acid metabolism in human amnion cells in monolayer culture. AB - Human amnion cells in primary monolayer culture were used as a model system to evaluate the regulation of arachidonic acid metabolism and prostaglandin E2 production in amnion. Amnion cells were incubated with carbon 14-labeled arachidonic acid, and after various times the distribution of radiolabeled arachidonic acid in the lipids of these cells were determined. After incubation for 72 hours, 91% of the total radiolabeled arachidonic acid incorporated into cellular lipids was present in glycerophospholipids, and 9% was present in neutral lipids. The formation of [14C]prostaglandin E2 from [14C]arachidonic acid was maximal after 8 hours. In these studies the effect of human fetal urine on arachidonic acid metabolism in these cells was investigated (the production of prostaglandin E2 by amnion cells is increased by treatment with fetal urine). In cells incubated with [14C]arachidonic acid in the incubation medium, treatment with fetal urine for 4 hours caused a threefold to fourfold increase in [14C]prostaglandin E2 production, yet there were no detectable differences in the content of [14C]arachidonic acid in specific glycerophospholipids or neutral lipids of the cells after such treatment. In other studies, amnion cells were preincubated for 72 hours with [14C]arachidonic acid, and thereafter the cells were treated with fetal urine for 24 hours. With fetal urine treatment the amount of [14C]arachidonic acid in triacylglycerols decreased significantly compared with that in nontreated cells, but the formation of [14C]prostaglandin E2 was not increased. Thus we suggest that in response to fetal urine, prostaglandin E2 is formed from arachidonic acid that is released from a highly specific, stimulus sensitive lipid pool or else from arachidonic acid that is derived from extracellular sources. PMID- 3098107 TI - Aldose reductase in the diabetic eye. XLIII Edward Jackson memorial lecture. AB - In diabetic cataracts aldose reductase initiates the cataractous process by converting glucose to sorbitol. The ensuing osmotic change, caused by sorbitol accumulation, adversely affects the lens permeability barrier so that the distribution within the lens of electrolytes, amino acids, and myo-inositol becomes grossly altered. These changes affect lens viability resulting in opacification. That aldose reductase triggers the process is shown by the fact that several structurally unrelated aldose reductase inhibitors prevent cataracts from occurring. Aldose reductase is also implicated in diabetic retinopathy and keratopathy. Aldose reductase functions in the retinal capillary pericytes, the cells first affected in microvascular abnormalities in diabetes. Additionally, retinal capillary basement membrane thickening can be prevented by aldose reductase inhibitors. Clinical trials are underway to determine the efficacy and safety of aldose reductase inhibitors in treatment of diabetic retinopathy. PMID- 3098109 TI - Ionomycin acts as an ionophore to release TRH-regulated Ca2+ stores from GH4C1 cells. AB - In the GH4C1 strain of rat pituitary cells, ionomycin, a divalent cation ionophore, induces a rapid and transient spike in cytosolic free Ca2+ concentrations [( Ca2+]i) similar to that induced by the Ca2+-mobilizing hormone thyrotropin-releasing hormone (TRH). To test directly the hypothesis that ionomycin causes the spike in [Ca2+]i by altering cellular Ca2+ stores, we have measured ionomycin-induced changes in 45Ca2+ fluxes and have compared these to previously characterized changes induced by TRH. Ionomycin (half-maximal concentration = 30 nM) rapidly (within 1 min) induced a release into the medium of 50-60% of cell-associated 45Ca2+, paralleling the spike in [Ca2+]i. The ionomycin-induced 45Ca2+ efflux was greater than with TRH, and TRH did not induce further 45Ca2+ efflux in the presence of ionomycin. Ionomycin pretreatment blocked induction of the spike in [Ca2+]i elicited by TRH but did not alter basal or TRH-induced enhancement of inositol phosphate levels. These results provide evidence that the spike in [Ca2+]i induced by ionomycin or TRH is produced largely by release of Ca2+ into the cytosol from the same intracellular pool, followed by rapid extrusion of the released Ca2+ into the extracellular space. However, unlike TRH, ionomycin appears to release cellular Ca2+ directly, acting as an ionophore, without the generation of known second messengers. PMID- 3098108 TI - Isolation of microtubule coils from platelets after exposure to aggregating agents. AB - The discoid shape of human blood platelets is supported by a circumferential microtubule (MT) organized in many loops or coils. A recent study reported from the authors' laboratory demonstrated that significant numbers of MT rings could be isolated from resting platelets by simultaneous exposure to detergent and a small amount of fixative. This method has been used in the present investigation to determine the number of MT coils obtained from platelets after activation by ADP, thrombin, and the calcium ionophore, A23187. Concentrations of the agonists that caused shape change and internal transformation in parallel samples did not influence the frequency of MT rings present in activated samples after treatment with fixative and detergent. As many or more MT coils were present 5, 15, 30, 60, 90, and 120 seconds after addition of an agonist as from the control. Statistical analysis revealed no significant difference between the number of isolated coils from controls and activated platelets at any time during early activation. Immunofluorescence microscopic examination of platelets stained with a monoclonal antibody to tubulin at intervals of 5, 15, 30, 60, 90, and 120 seconds after activation on glass surfaces confirmed the suggestion that platelet MTs are resistant to disassembly during the early response to stimulation. PMID- 3098110 TI - Determinants of Ca2+-dependent stress maintenance in skinned swine carotid media. AB - Ca2+-dependent stress maintenance without proportional myosin light chain (MLC) phosphorylation was demonstrated in the detergent-skinned swine carotid media when [Ca2+] was reduced from high to intermediate concentrations (Chatterjee, M., and R. A. Murphy. Science Wash. DC 221: 464-466, 1983). In this study of the same preparation, we examined the influence of the initial [Ca2+] and MLC phosphorylation levels on the formation of a stress maintaining state (the "latch" state). Fibers were contracted with 0.82, 1.3, 2.1, or 7.2 microM Ca2+ and then exposed to a lower [Ca2+] to determine the magnitude and Ca2+ sensitivity of stress maintenance. MLC phosphorylation levels were measured in all strips. The magnitude of the stress that rapidly developed was dependent on the initial activating [Ca2+]. The Ca2+ sensitivity of stress maintenance appeared to be independent of the initial levels of stress and MLC phosphorylation. However, the magnitude of the maintained stress was dependent on the initial levels of Ca2+. Only two values for half-maximal responses were evinced in all Ca2+-dependent stress curves: 1.4 X 10(-6) M Ca2+ for rapid stress development and 3.1 X 10(-7) M for stress maintenance. Cumulative [Ca2+]-response curves were shown to result in a decreased maximal stress response and an increase in the apparent Km compared with curves determined by responses to single [Ca2+] exposures. This was associated with a time- and stress-related deterioration of the preparation. The latter was not prevented by exogenous calmodulin or leupeptin (an effective inhibitor of an endogenous Ca2+-dependent protease shown to disrupt the cellular cytoskeleton).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098111 TI - Renal effects of angiotensin II: modulation by calcium and cyclooxygenase products. AB - Modulation of angiotensin II effects on renal function by extracellular calcium levels and cyclooxygenase products was evaluated using the isolated perfused rat kidney. Kidneys from normal male Sprague-Dawley rats were perfused at constant pressure. After base-line assessment of function, angiotensin II was administered as a bolus and constant infusion; group 1 with normal ionized calcium and 1.2 ng/min angiotensin II, group 2 with normal ionized calcium and 0.6 ng/min angiotensin II, group 3 with low ionized calcium and 1.2 ng/min angiotensin II, and group 4 with indomethacin, low ionized calcium, and 1.2 ng/min angiotensin II. Angiotensin II caused a marked fall in inulin clearance (CIn) in groups 1 and 2. With low ionized calcium (group 3), angiotensin II increased resistance to the same degree as in group 2, but in contrast to group 2, CIn was unchanged. Kidneys perfused with indomethacin (group 4) had marked angiotensin II-induced declines in CIn that rapidly returned to base line despite persistently elevated resistance. Thus the results demonstrated that both calcium and cyclooxygenase products may directly modulate the effects of angiotensin II on renal function. These effects involve more than modulation of angiotensin II-induced vasoconstriction. PMID- 3098112 TI - Pulmonary vascular pressure-flow relationship in canine oleic acid pulmonary edema. AB - We tested the hypothesis that the increased impedance to flow in canine oleic acid (OA) lung injury is predominantly due to an increase in effective downstream pressure (EDP), obtained by extrapolating to zero flow the linear portion of the pulmonary artery pressure (PAP)/flow (Q) relationship. PAP-Q coordinates were obtained in eight anesthetized, O2-ventilated dogs by varying Q through systemic arteriovenous fistulae. PAP-Q lines were obtained before and approximately 5 h after injection of OA. A second group of six dogs served as a time control (TC) group. There was a linear relationship between PAP and Q in both experimental and control groups (mean r value 0.948). The presence of pulmonary edema in the OA group caused the EDP to almost double, from 7 to 12 mmHg (P less than 0.01). In contrast, EDP remained constant in TCs. Incremental vascular conductance (IVC), slope of the PAP/Q line, decreased (P less than 0.05) a similar amount in both groups. The above findings are consistent with the modeling of the pulmonary circulation according to a Starling resistor in that large amounts of edema changed EDP but not incremental conductance. PMID- 3098113 TI - Disruption of the blood-brain barrier in cerebrum and brain stem during acute hypertension. AB - The purpose of this study was to examine hemodynamic mechanisms of protection of the blood-brain barrier in the brain stem during acute hypertension. We used a new method to examine the microcirculation of the brain stem. Intravital fluorescent microscopy and fluorescein-labeled dextran were used to evaluate disruption of the blood-brain barrier during acute hypertension in rats. During control conditions, pressure (servo null) in arterioles (60 microns in diameter) was 50 +/- 2% (mean +/- SE) of systemic arterial pressure in the cerebrum and 67 +/- 1% of systemic arterial pressure in the brain stem (P less than 0.05 vs. cerebrum). In the cerebrum, pial venous pressure increased from 7 +/- 1 to 25 +/- 2 mmHg during acute hypertension, and there was marked disruption of the blood brain barrier in venules (26 +/- 2 leaky sites). In contrast, in the brain stem, pial venous pressure increased from 4 +/- 1 to only 8 +/- 1 mmHg (P less than 0.05 vs. cerebrum), and there was minimal disruption of the blood-brain barrier in venules (1.5 +/- 0.6 leaky sites, P less than 0.05 vs. cerebrum). During acute hypertension, increases in blood flow (microspheres) were less in brain stem than in cerebrum. The findings suggest distribution of vascular resistance differs in the brain stem and cerebrum under control conditions, whereas large arteries account for a greater fraction of resistance in cerebrum; pial venous pressure increases less in brain stem than cerebrum during acute hypertension, so that the blood-brain barrier is protected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098114 TI - Aminophylline and interstitial adenosine during sustained exercise hyperemia. AB - We tested the hypothesis that an increase in interstitial fluid (ISF) adenosine concentration contributes to vasodilation of high oxidative skeletal muscle during sustained free-flow exercise. Canine calf muscles were stimulated at 3 Hz for 10 min before and after the infusion of the adenosine receptor antagonist aminophylline (10 mg/kg). The vasodilation that occurred during aminophylline infusion was allowed to decay before the postaminophylline exercise period was begun. This dose of aminophylline shifted the response to infused adenosine 20 fold during rest and reduced the response to a standard dose by 90% during exercise. Aminophylline had no significant effect on blood flow or on O2 consumption at rest or during exercise. Adenosine release (venous minus arterial plasma concentration times plasma flow) increased during 3-Hz exercise both before and after aminophylline infusion, but venous plasma adenosine concentration did not increase in either case. We developed a mathematical model of adenosine movement between ISF and plasma to help us judge whether to use adenosine release or venous concentration as an index of ISF adenosine and decided that venous concentration should be used. We conclude that aminophylline has no effect on sustained 3-Hz exercise hyperemia because under these conditions ISF adenosine concentration does not increase. PMID- 3098115 TI - Role of vasopressin in the cardiovascular response to hypoxia in the conscious rat. AB - Previous experiments have demonstrated that hypoxia stimulates the release of arginine vasopressin in conscious animals including the rat. The present study was designed to test whether AVP may exert a vasoconstrictor influence during hypoxia at varying levels of CO2. Systemic hemodynamics were assessed in conscious rats for 30 min under hypocapnic hypoxic, isocapnic hypoxic, hypercapnic hypoxic, and room air conditions. Progressive effects on heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were observed with varying CO2 under hypoxic conditions. Hypocapnic hypoxia [arterial PO2 (PaO2) = 32 Torr; arterial PCO2 (PaCO2) = 22 Torr] caused HR and CO to rise and TPR to fall. Isocapnic hypoxia (PaO2 = 36 Torr; PaCO2 = 35 Torr) was associated with no significant changes in HR and CO or TPR, whereas hypercapnic hypoxia (PaO2 = 35 Torr; PaCO2 = 51 Torr) caused HR and CO to fall and TPR to rise. Room air time control experiments were associated with no change in measured hemodynamic variables. To determine the possible role of circulating AVP on these cardiovascular responses, additional experiments were performed where the specific V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP (10 micrograms/kg iv) was administered at the midpoint of hypoxic exposure. Antagonist administration had no effect on hypocapnic hypoxic animals or animals breathing room air; however, blood pressure and TPR were significantly reduced by d(CH2)5Tyr(Me)AVP in both isocapnic and hypercapnic hypoxic animals. The heart rate response to hypoxia at the various CO2 levels was unaffected; however, cardiac output and stroke volume were increased after V1-antagonism in the isocapnic and hypercapnic hypoxic animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098116 TI - Interdependency of local capillary density, blood flow, and metabolism in rat brains. AB - Previous investigations have established a strong correlation between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU). In the present study the relationship between density of perfused brain capillaries and LCBF or LCGU was investigated in conscious and anesthetized rats. Perfused capillaries were stained by labeling the plasma with the gamma globulin-coupled fluorochromes, fluorescein isothiocyanate (FITC) and lissamine-rhodamine B 200 (RB 200). The density of perfused capillaries was determined in 12 different brain structures by fluorescence microscopy of embedded brain sections following coronal sectioning in a cryostat. Significant differences were found among brain structures investigated; the lowest density of perfused capillaries was found in the white matter (e.g., corpus callosum 162 fragments/mm2), whereas the highest values were determined in the structures of the auditory system (e.g., inferior colliculus 810 fragments/mm2). LCBF and LCGU were measured in two separate groups of rats using standard autoradiographic methods. In all three experimental groups, the same structures were identified and measured with a high degree of accuracy and local resolution. Density of perfused capillaries correlated well with LCBF (r = 0.93) and even better with LCGU (r = 0.97). In addition to the relationship between LCGU and LCBF established by earlier studies, these data show the intimate interrelationship between LCGU, density of perfused capillaries, and LCBF. PMID- 3098117 TI - Olfactory bulbectomy prevents anti-gonadal effect of exogenous melatonin in male hamsters. AB - When male Golden hamsters are maintained on short days (less than 12.5 h of light/day) the testes gradually regress. This testicular regression is due to an inhibitory effect of pineal gland melatonin on gonadotropin secretion. A previous report from the author's laboratory has indicated that olfactory bulbectomy (BX) will prevent the testicular regression associated with short photoperiod. The present study examined whether BX would also prevent the testicular regression associated with exogenous melatonin (MEL) injections. Male Golden hamsters were BX or sham (SH) BX at 23-28 days of age and were maintained on 14:10 light-dark cycle. Six weeks following surgery, one half of each surgical group began receiving injections of melatonin (15 micrograms sc), whereas the other half was injected with vehicle at 1600 daily. The testes size of the SH group injected with MEL progressively decreased, whereas the testes of all other groups remained large. These results indicate that BX prevents the testicular regression associated with short photoperiod by interfering with the antigonadotropic effect of melatonin. PMID- 3098118 TI - Comparison of clonidine and lithium in the treatment of mania. AB - The authors compared the antimanic effects of clonidine with lithium carbonate in a double-blind crossover design with 24 volunteers. Lithium was observed to be more effective than clonidine. Some patients reported experiencing hypotension (N=8) and depression (N=7) while taking clonidine. PMID- 3098119 TI - Diagnosis-related groups and exempt psychiatric units. PMID- 3098120 TI - Infantile (desmoid type) fibromatosis with extensive ossification. AB - Solitary congenital or infantile (desmoid-type) fibromatosis is a benign, but potentially locally aggressive lesion that is best treated by wide local excision. It has been confused with congenital fibrosarcoma and other soft-tissue malignant tumors. To our knowledge, ossification has not been reported previously in this lesion. A case of ossifying solitary congenital fibromatosis is presented with a discussion of its differential diagnosis and histologic distinction from other soft-tissue lesions, including soft-tissue and parosteal osteosarcoma. PMID- 3098121 TI - Inhibition of polyamine biosynthesis by alpha-difluoromethylornithine in African trypanosomes and Pneumocystis carinii as a basis of chemotherapy: biochemical and clinical aspects. AB - The symposium provided dramatic evidence of the value of the use of polyamine inhibition via alpha-difluoromethylornithine (DFMO, eflornithine) for advances in chemotherapy of Trypanosoma brucei gambiense sleeping sickness and Pneumocystis carinii pneumonia in acquired immune deficiency syndrome (AIDS) and also for further understanding the metabolic importance of the ubiquitous polyamines in these organisms. PMID- 3098122 TI - The radiographic evaluation of appendiceal calcification due to schistosomiasis. AB - In a 6-month period, 25 appendices with histological involvement by schistosomiasis were radiographed. Eleven showed varying degrees of radiographically detectable calcification having a spotty, linear, or amorphous pattern affecting either a short segment or the whole appendix. Four of these appendices had a mixed pattern and one also had nodular calcification in the mesoappendix. In only 1 patient was the appendiceal calcification visible on preoperative abdominal radiographs. In 5 asymptomatic patients, not submitted to surgery, appendiceal calcification was detected during radiologic evaluation of urinary schistosomiasis. PMID- 3098123 TI - Urinary tract lesions due to Schistosoma haematobium infection assessed by ultrasonography in a community based study in Niger. AB - The comparative prevalences of urinary tract lesions in 2 villages where urinary schistosomiasis was endemic and in a control village free from infection were assessed by ultrasonography. Of the 822 residents greater than 4 years of age in the first village (Seberi) where the prevalence of infection was 57%, 279 were examined by ultrasonography. The prevalence of bladder lesions was 71% in those 5 14 years of age, 57% among adult men, and 24% among women in this endemic village, compared to 10%, 16%, and 6%, respectively, in the control village. Renal lesions were infrequent among adults and there was no significant difference in the rates between Seberi and the control village. Among children, moderate hydronephrosis was absent in the control village, but was observed in 19% of the boys 5-14 years of age and 2% of the girls 5-14 years of age in Seberi. Sixty schoolchildren of the second endemic village with urinary egg counts greater than or equal to 100 eggs/10 ml of urine were examined by ultrasonography. The overall prevalence and the severity of bladder lesions in the 2 endemic villages were significantly related to the urinary egg count. PMID- 3098124 TI - Migration of Schistosoma mansoni in normal and passively immunized laboratory rats. AB - Normal and passively immunized Fischer rats were infected with 75Se selenomethionine-labeled cercariae of Schistosoma mansoni. Migration of the parasites from skin to lungs to liver was monitored by autoradiographic analyses of these sites. Labeled parasites migrated from skin to lungs with high efficiency in normal and immune rats; disappearance of labeled parasites from the lungs was slower in immune rats. Labeled parasites accumulated in the liver, reaching maximal values by 11 days post-infection in both groups and remaining constant through day 21. Half the number of labeled parasites were detected in the liver of immune rats. The total number of labeled parasites detected in the skin, lungs, and liver was constant through day 5, then declined to about 60% of this value by day 11 in both groups. Over the next 10 days, the rate of decline decreased significantly in normal rats but did not change in immune rats. By day 21 post-infection, nearly 50% fewer labeled parasites were detectable in immune rats. We conclude that a subpopulation of parasites in the lungs is the target of protective antibody in the serum used for passive immunization. Target parasites, retained longer in the lungs, were probably prevented from migrating successfully to the liver. Another parasite subpopulation migrated to the liver with normal kinetics. Lung schistosomula isolated from normal and passively immunized rats were transferred by intravenous injection into recipient rats and their continued migration from lungs to liver compared. No differences in portal perfusion worm yields were detected in normal recipients; equally reduced yields were detected in passively immunized recipients. We conclude that the effects of antibodies during week 1 post-infection were insignificant or reversible. PMID- 3098125 TI - Liver fibroblast proliferation in murine schistosomiasis. AB - Liver fibrosis in schistosomiasis is associated with prominent accumulations of fibroblasts. Primary cell cultures were prepared from the fibrotic livers of Schistosoma mansoni-infected mice, and cells with the appearance of fibroblasts by light microscopy were isolated from these cultures. Proliferation of these cells was examined in coculture experiments with syngeneic inflammatory cells. T cell-enriched mononuclear cells from spleens of S. mansoni-infected or normal mice, and Kupffer cell/macrophages from fibrotic liver all stimulated the proliferation of liver fibroblasts, as measured by 3H-thymidine uptake. Primary cultures of mouse skin fibroblasts showed similar responses to coculture, but an established fibroblast line, 3T3, was unresponsive. Cell-free supernatant medium from coculture experiments did not affect fibroblast proliferation, perhaps because of the requirement for serum in the culture medium. Liver fibroblasts derived from this disease model may be especially suitable for study of the interaction between tissue inflammation and fibrosis. PMID- 3098126 TI - Detection of high molecular weight eosinophil chemotactic factor in murine schistosomiasis sera. AB - Eosinophil chemotactic activity in sera from mice undergoing an acute stage of schistosomiasis japonica and mansoni was examined. Eosinophilotactic activity in the serum was dependent on the dose and time of infection. Eosinophilotactic activity in sera from S. japonicum-infected mice was higher than that from S. mansoni-infected mice when they were compared at the comparable dose and time of infection. After gel chromatography on Sephadex G-200, eosinophilotactic activity in sera from mice infected with 30 cercariae of S. japonicum for 5 weeks was detected in the high molecular weight component. On the other hand, when sera from mice infected with 30 cercariae of S. japonicum for 8 weeks was chromatographed through Sephadex G-200 columns, eosinophilotactic activity was segregated into high (greater than 455,000) and low (less than 13,000) molecular weight components. High molecular weight ECF in sera from mice infected with 30 cercariae of S. japonicum for 8 weeks had high affinity to Con A, and was stable to heating or pronase digestion, but was sensitive to periodate oxidation, indicating its polysaccharide or glycoprotein nature. This high molecular weight ECF could be adsorbed by, and eluted from immunoaffinity beads coated with rabbit IgG anti-S. japonicum adult worm antibody. Thus, at least some part of circulating high molecular weight ECF would be derived from adult parasites. PMID- 3098127 TI - Identification of a genus-specific Schistosoma mansoni soluble egg antigen reactive with the serum of infected patients. AB - The ability of serum samples obtained from humans with schistosomiasis mansoni to recognize Schistosoma mansoni soluble egg antigens (SmSEA) was assessed by the enzyme-linked immunotransfer blot (EITB) method. The sera from 15 infected patients before and 2 years after treatment with oxamniquine (n = 30) recognized bands ranging in molecular weight from 9 to 200 Kd. A 31 Kd component of SmSEA was recognized by all infection sera, but not by normal human serum. The sera from 2 humans infected with S. haematobium and 2 with S. japonicum also recognized the 31 Kd band present in SmSEA, whereas those from 2 humans infected with Fasciola hepatica did not. The 31 Kd antigen was isolated by electrophoresing SmSEA through a 15% SDS-acrylamide gel, followed by excision and electroelution of the 31 Kd band. The purified 31 Kd was used in conjunction with ELISA at a concentration of 1 microgram/ml to confirm the apparent genus specificity of this protein. Thus, the sera of patients infected with S. mansoni, S. haematobium, or S. japonicum were clearly reactive in ELISA, whereas normal human serum or sera from patients with F. hepatica were negative. In conclusion, the 31 Kd protein appears to be a good candidate for developing a screening assay for the immunodiagnosis of schistosomiasis. PMID- 3098128 TI - Intraarterial chemotherapy and hyperthermia for pain control in patients with recurrent rectal cancer. AB - For the majority of patients with unresectable recurrence of rectal cancer, persistent pain is the most distressing problem. This brief study describes a method to control pain in 10 patients with unresectable rectal cancer confined to the pelvis after standard therapy failed. All of the patients had percutaneous placement of infusion catheters in both internal iliac arteries. A continuous intraarterial infusion of 800 mg/m2 of 5-fluorouracil per day was given for 7 days and 10 mg/m2 of mitomycin C was administered as a bolus injection on the seventh day only. Four patients also received whole body hyperthermia by way of a Erbotherm 434 mHz microwave generator on the second and fifth days of infusion. Relief of pain occurred in three of the six patients who received intraarterial chemotherapy only. All four patients who also received hyperthermia achieved prolonged pain relief when it was added. We have concluded that intraarterial chemotherapy may be beneficial in patients with uncontrolled pelvic pain due to recurrent rectal cancer. The addition of hyperthermia may augment the benefit. PMID- 3098129 TI - Topical sodium cromoglycate in atopic dermatitis. A disappointing but informative trial. AB - Forty children with atopic eczema requiring topical steroids entered a double blind group comparative study over 12 weeks and were randomized to either 4% sodium cromoglycate (SCG) in an oil-in-water cream or matching placebo cream. The eczema was evaluated on area charts for 20 parts of the body at five clinic visits. In addition, the families kept diaries on symptoms and treatment. After 3 weeks there were small but statistically significant decreases in severity scores recorded at the clinical visits in the SCG group compared with small increases in the placebo group. However, there were no statistically significant differences in the diary card data during the first 3 weeks of treatment or in any other period, nor were significant differences found in any efficacy data collected during the other 9 weeks of the trial. There were no marked differences in treatment opinions, unusual symptoms, skin infections, use of topical steroids or drugs, or acceptability data between the groups. Staphylococcus aureus was found once or twice in cultures from eczema lesions in 31 of 40 children with no marked group difference. The trial showed that there is great need for improved information, family support and topical as well as general treatment in childhood atopic eczema, but topical SCG did not relieve the patients' eczema. PMID- 3098130 TI - Inhibition of leukotriene (SRS-A)-mediated acute lung anaphylaxis by azelastine in guinea pigs. AB - Azelastine hydrochloride, chemically known as 1(2H)-phthalazinone, 4-[(4 chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepine-4-yl)-, monohydrochloride, is a novel, orally effective, long-acting, antiallergic/antiasthmatic agent. The ability of azelastine and selected antiallergic drugs to inhibit SRS-A (leukotriene)-mediated acute lung anaphylaxis in guinea pigs (Konzett-Rossler method) was investigated. Azelastine and ketotifen were administered p.o. 2 and 24 h before antigen challenge; disodium cromoglycate (DSCG) was administered i.v. immediately before antigen challenge. The oral dose of azelastine required to inhibit leukotriene-mediated allergic bronchospasm by 50% (ID50: mg/kg) was 0.063 at 2 h and 0.120 at 24 h. Ketotifen at a dose of 0.05 to 10 mg/kg at 2 and 24 h, p.o., as well as DSCG at a dosage of 0.3 to 10 mg/kg at 0 min, i.v., produced weak, inconsistent and nondose-related antianaphylactic effects. Azelastine is an orally effective and long-acting inhibitor of in vivo synthesis and/or release of leukotrienes. PMID- 3098131 TI - Ro 15-1788 for postoperative recovery. A randomised clinical trial in patients undergoing minor surgical procedures under midazolam anaesthesia. AB - In a double-blind randomised study, 100 women who underwent induced abortion under midazolam anaesthesia were given the benzodiazepine antagonist Ro 15-1788 or placebo after termination of anaesthesia. Recovery was assessed by means of a modified Steward coma scale. Following incremental doses of Ro 15-1788, 56% of the patients were fully awake within 3 minutes and 92% after 5 minutes, which was significant compared to the placebo group. The median duration of amnesia was 91 minutes after Ro 15-1788 compared to 121 minutes in the placebo group (p less than 0.001). The median dose of Ro 15-1788 was 0.4 mg. A slight positive correlation between total dose of Ro 15-1788 and total amount of midazolam was found. Nausea and/or vomiting were found to be more frequent in the Ro 15-1788 group, but otherwise we found no differences between groups with regard to either side effects or cardiorespiratory function. Ro 15-1788 is evidently an effective antagonist to the sedation induced by midazolam. PMID- 3098132 TI - Topical nitroglycerin. A safeguard against pressor responses to tracheal intubation. AB - In order to attenuate the pressor response to intubation of the trachea we have studied the effects of 2% nitroglycerin ointment rubbed on the forehead approximately 12 minutes prior to intubation. A double blind, randomized design was used in 56 consecutive patients. Of these, 30 patients received the ointment while 26 patients formed the control group. The maximum rise in the systolic arterial pressure was significantly lower (p less than 0.001) in the group (7.66 mmHg, 6.2%) as compared to the control group (25.7 mmHg, 20.2%). The rise in arterial pressure persisted for up to 4 minutes in the control group, but lasted for only one minute in the nitroglycerine group. The pulse rate, however, increased in both groups to an equal extent. We have found the application of 2% nitroglycerine ointment to be a safe, inexpensive, comfortable and effective means of attenuating the pressor response to intubation of the trachea. PMID- 3098133 TI - The effects on gas exchange of a large mediastinal tumour. AB - A 14-year-old boy with a mediastinal tumour large enough to cause dyspnoea at rest was anaesthetised for a biopsy. The tumour was believed to compress the tracheal bifurcation. After tracheal intubation, the expiratory breath sounds were heard to be intermittent. The expiratory flow pattern showed irregularities synchronous with the electrocardiogram. With constant flow inflation, the inspiratory pressure profile was suggestive of mechanical obstruction with a resistance which decreased during inspiration. The airway deadspace was greatly reduced, suggesting that the obstruction was near the tracheal tube opening and that there was pooling of carbon dioxide behind this obstruction. The alveolar deadspace fraction was increased and the shape of the carbon dioxide single breath test suggested severe airway obstruction. These findings can be explained on the basis of large airway obstruction, partly intermittent because of the heart's movement, and also reduced lung volume and uneven gas distribution caused by the tumour and pleural fluid. PMID- 3098134 TI - Alfentanil in an anaesthetic technique for penetrating eye injuries. AB - Alfentanil in three doses (10, 20 and 30 micrograms/kg) was added to an anaesthetic technique suitable for penetrating eye injuries. All three doses proved effective in abolishing the marked present response to tracheal intubation which occurs with this technique, but at least 20 micrograms/kg was needed to obtund the heart rate response significantly and to facilitate early intubation. Transient hypotension and bradycardia occurred in some patients who received the highest dose of alfentanil. The incidence of postoperative sequelae was small in all groups. Thus, the optimal dose of alfentanil in an anaesthetic technique for penetrating eye injuries appears to be 20 micrograms/kg. PMID- 3098135 TI - Liquid chromatographic determination of amino acids after gas-phase hydrolysis and derivatization with (dimethylamino)azobenzenesulfonyl chloride. PMID- 3098136 TI - Large-scale separation of lipids from organochlorine pesticides and polychlorinated biphenyls using a polymeric high-performance liquid chromatographic column. PMID- 3098137 TI - Epidural morphine in children: pharmacokinetics and CO2 sensitivity. AB - The effects of epidural morphine (50 micrograms X kg-1) after abdominal and urologic surgery were studied in 20 children ranging in age from 2 to 15 yr and weighing between 9 and 54 kg. The onset and the duration of analgesia were 30 +/- 12 min and 19.5 +/- 8 h, respectively (mean +/- SD). Side effects were pruritus (4/20), nausea and vomiting (8/20), and urinary retention (4/14). No apnea was observed. Ventilation control was studied in seven children. No significant change in resting respiratory variables occurred after both surgery and epidural morphine injection. However, the slope of the ventilatory response to CO2 was significantly (P less than 0.05) decreased after surgery but before morphine, as compared with its preoperative control value (0.84 +/- 0.44 versus 1.51 +/- 0.72 l X min-1 X mmHg-1), and remained low for 22 h after epidural morphine (0.90 +/- 0.57 l X min-1 X mmHg-1). Sixty minutes after morphine injection, the plasma morphine concentration was always less than 12 ng X ml-1 in the seven children studied. Pharmacokinetic parameters were similar to those observed after epidural injection of morphine in adults, except for a shorter terminal half-life (73.8 +/ 41.6 min) attributed to a greater total body clearance of morphine in the children (28.3 +/- 3.4 ml X min-1 X kg-1). It is concluded that epidural morphine provides effective and prolonged analgesia in children after abdominal and urologic surgery and that it is associated with prolonged respiratory depression that requires close monitoring for at least 24 h. PMID- 3098138 TI - Cerebral metabolism and EEG during combination of hypocapnia and isoflurane induced hypotension in dogs. AB - Isoflurane (ISF)-induced hypotension causes equal reductions of cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) so that no disturbance of cerebral energy stores or metabolites occurs. While hypocapnia during ISF-induced hypotension causes a further reduction of CBF, the effects on cerebral energy stores and metabolites produced by combining hypocapnia with ISF induced hypotension are not known. This study examined the effect of hypocapnia (PaCO2 = 20 mmHg) on CMRO2, the electroencephalogram (EEG), and levels of adenine nucleotides, phosphocreatine, lactate, pyruvate, and glucose in brain tissue in 12 dogs during ISF-induced hypotension. All dogs were examined at: normocapnia with normotension; hypocapnia with normotension; hypocapnia combined with ISF induced hypotension to cerebral perfusion pressures of 60, 50, and 40 mmHg; and restoration of normocapnia with normotension. In six dogs CMRO2 was determined, and the EEG was evaluated using compressed spectral analysis. In the other six dogs brain tissue metabolites were determined. Hypocapnia combined with ISF induced hypotension (all levels) caused a decrease of the power of the beta-2 spectra, an increase of the power of the alpha and beta-1 spectra, but no change in total power of the EEG. There was no change in cerebral energy stores or brain tissue metabolites. CMRO2 was reduced by approximately 27%. Thirty minutes after restoration of normocapnia with normotension, cerebral metabolites remained unchanged and CMRO2, and the power of the alpha, beta-1, and beta-2 spectra of the EEG returned to control values. These results suggest no adverse effect on cerebral metabolism or function during hypocapnia combined with ISF-induced hypotension. PMID- 3098140 TI - Influence of sublingual nitroglycerin on the digital circulation of man. AB - By means of the digital rheoplethysmographic (RPG) method, the effect of sublingually administered nitroglycerin (NTG), 1/200 gr (0.3 mg), on the digital circulation was studied in 17 normal subjects and 5 patients with ischemic heart disease and angina pectoris. NTG produced dilatation of all digital vessels, reflected especially by increases in total digital volume. NTG produced marked changes in the dicrotic notch of the pulse wave, noted also in inflow volume curves but not in outflow volume curves. The dicrotic notch was displaced later on the descending limb of the digital pulse wave and became deeper and more prominent after NTG. It is suggested that NTG produces disproportionate dilatation of the arterial system, having its greatest effect on arteries near the heart, including the coronaries and great vessels branching off the aorta, and on left intraventricular cavity pressure. This greater regional vasodilatation of vessels near the heart could delay closure of the aortic valve, producing a delayed and prominent dicrotic notch of the pulse wave. PMID- 3098139 TI - Cardiorespiratory effects and kinetics of intrathecally injected D-Ala2-D-Leu5 enkephalin and morphine in unanesthetized dogs. AB - In unanesthetized dogs prepared with chronic tracheostomies and chronically implanted intrathecal (IT) catheters having openings in the cisterna magna and lumbar region, lumbar IT injection of D-Ala2-D-Leu5-enkephalin (DADL, 1-10 mg) and morphine (3-30 mg) produced a dose-dependent depression of the slope of the CO2 response function (minute expired volume [VE] vs. end-tidal [ET] CO2) as investigated by a modified Read rebreathing technique. The maximum depression occurred less than 3 h after IT injection of either agent and lasted as long as 12 h. The depression was totally reversed by naloxone (0.4 mg/kg, iv). Naloxone alone had no effect on ventilatory function. After 10 mg DADL, there was no significant change in heart rate (HR), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), cardiac output (CO), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), or PaO2 during the 3 h postinjection. In contrast, PaCO2 was significantly elevated and pH significantly decreased (P less than 0.05). Naloxone administration after high-dose IT DADL resulted in a doubling of MABP, MPBP, CO, and SVR that lasted approximately 20 min. In concurrently measured cisternal cerebrospinal fluid (CSF) levels, both morphine and DADL displayed peak levels by 30-60 min. The lumbar CSF clearance curves for both agents were fitted with a two-compartment intravenous bolus model. The t 1/2 alpha was 13.8 +/- 3.6 min for DADL and 9.4 +/- 1.6 min for morphine (mean +/- SE). The t 1/2 beta was 101.3 +/- 17.7 min for DADL and 116.7 +/- 27.9 min for morphine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098141 TI - Double-blind crossover trial with oral sodium cromoglycate in children with atopic dermatitis due to food allergy. AB - Thirty-one children with atopic dermatitis, aged 6 months to 10 years, were selected for this trial. All had historical, clinical, and laboratory evidences that allergy to food was the cause of exacerbations of eczema. Either oral sodium cromoglycate (SCG) or a matching placebo was administered orally for 8 weeks, followed by the alternative treatment for a further 8-week period. During the first 4 weeks of each treatment period, patients remained on an exclusion diet. During the second 4 weeks, the offending food(s) was reintroduced into the diet. The severity of the eczema and the changes in severity as a result of diet or challenge were measured both by the clinician (using body diagrams) and by parents (using a daily diary card). Analysis of the clinician's scoring and the patient's diary card scores demonstrated a statistically significant difference in favour of SCG, especially in the group where the placebo preceded the active treatment. Sodium cromoglycate does seem to reduce the exacerbations of atopic dermatitis caused by food allergens. PMID- 3098142 TI - [M monoclonal macroglobulinemia induced in BALB/C mice. Effect on blood cholesterol and its significance]. AB - BALB/C mice have been inoculated with a monoclonal IgM secreting hybridoma and have developed an hypocholesterolemia strongly dependent of the hypermacroglobulinemia M obtained (P less than 0.001). Cholesterolegram shows cholesterol is carried on the monoclonal IgM fraction. This result has been established in comparison with a lot of mice treated with the same no secreting hybridoma and a lot of untreated-mice, in these cases cholesterolemia is not modified. The whole aminoacids sequence of this IgM being nearly achieved, it is thinked of check the hypocholesterolemic activity of several parts of this immunoglobulin. PMID- 3098143 TI - Experimentally induced Brucella abortus infection in pregnant goats. AB - Pregnant goats in midgestation (7 to 16 weeks) were conjunctivally exposed to Brucella abortus strain 2308 to evaluate their applicability as an animal model for bovine brucellosis. Brucellae were isolated from uterine fluid and/or placental specimens of 10 of 12 does at parturition. Six of the 10 infected does delivered dead fetuses and 1 of the 10 delivered live, premature twins. Dead fetuses typically contained brucellae in multiple tissues, whereas brucellae generally were not isolated at birth from live kids. After parturition, B abortus was excreted in the milk and uterine fluids of the infected does. At necropsy (6 weeks after parturition), organisms in the doe were primarily in the uterus and in the lymph nodes that drained the mammary glands, uterus, and head. Brucella abortus was most often isolated from the cranial lymph nodes of neonates that had remained with their dam for 6 weeks after parturition. Serum anti-Brucella antibody concentrations were determined by use of standard tube agglutination, mercaptoethanol agglutination, Rivanol plate tests, card tests, complement fixation, hemolysis-in-gel tests, and an enzyme-linked immunosorbent assay. Serologic responses were detected 2 to 3 weeks after exposure and remained detectable until parturition. Antibody titers increased after parturition in does shedding B abortus at parturition. Anti-Brucella antibody was not detected in neonates before colostrum intake. The neonate's postcolostral titers were similar to those in the dam at the time of parturition. Milk anti-Brucella antibody was detected in milk (milk ring test) from infected and noninfected mammary glands.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098144 TI - Thoracoabdominal motion in response to treadmill and cycle exercise. AB - The present study was designed to assess differences in compartmental contributions to ventilation between cycle pedaling and treadmill walking. Eight subjects performed submaximal cycle (CE) and treadmill (TM) exercise. The mean maximal work loads were not significantly different between the 2 modes of exercise. Ventilation (VE), oxygen uptake (VO2), and respiratory inductance plethysmography (RIP) were measured continuously during both modes of exercise. During both TM and CE, VE measured by RIP was found to correlate significantly with VE measured by pneumotachometer. Although the ventilation/work load relationship for CE exceeded that for TM in all subjects, when changes in rib cage (RC) and abdominal (ABD) tidal volume responses were expressed relative to changes in VE, no significant differences were found between TM and CE (RC, p greater than 0.05; ABD, p greater than 0.05). When these changes in tidal volume were expressed relative to changes in work load and independent of ventilation, there were no significant differences between separate compartmental responses during TM or CE (RC, p greater than 0.05; ABD, p greater than 0.05). We conclude that while absolute degrees of ventilation at a given work load differ between cycling and walking, the postural and ventilatory differences between these forms of exercise do not appear to induce differences in the relative contributions of the rib cage or the abdomen to tidal breathing. PMID- 3098145 TI - The effect of exercise on pulmonary gas exchange in patients with severe chronic obstructive pulmonary disease. AB - The effect of low level, steady-state exercise on pulmonary gas exchange was studied in 7 patients with severe chronic obstructive pulmonary disease and pulmonary hypertension. Exercise led to a significant fall in the arterial PO2 from 76 +/- 10 to 63 +/- 8 mm Hg, a rise in the arterial PCO2 from 56 +/- 6 to 62 +/- 8 mm Hg, and a fall in the mixed venous PO2 from 38 +/- 2 to 32 +/- 2 mm Hg. There was, however, no significant change in the degree of ventilation-perfusion inequality as quantified by the multiple inert gas technique and no evidence that impaired O2 diffusion was playing a role in the increased hypoxemia. We conclude that the worsening hypoxemia with exercise in patients with severe COPD is due to an inadequate ventilatory response (leading to a rise in arterial PCO2) and the impact of a decreased mixed venous PO2 on the end-capillary PO2 of low VA/Q lung units and shunt. PMID- 3098146 TI - Endotoxin-induced changes in pulmonary hemodynamics and respiratory mechanics. Role of lipoxygenase and cyclooxygenase products. AB - We investigated the role of leukotrienes and cyclooxygenase products in endotoxin induced pulmonary vascular and airway changes. In 11 conscious sheep, measurements of pulmonary vascular resistance (PVR), lung resistance (RL), arterial PO2, leukocyte count (WBC), and plasma thromboxane B2 (TxB2), 6-keto PgF1 alpha and PgF2 alpha were obtained, before and at predetermined intervals after a 10-min infusion of E. coli endotoxin (0.3 microgram/kg). On a separate occasion, 5 sheep received an infusion of the leukotriene end-organ receptor antagonist FPL-57231 (0.7 to 1 mg/kg/min), before and for as long as 4 h after endotoxin infusion; and 6 sheep received a single injection of the cyclooxygenase inhibitor indomethacin (2 mg/kg) 1 h before endotoxin infusion. Endotoxin caused a biphasic response with an increase in mean PVR and RL to 441 and 353% of baseline, respectively, during the early phase (0 to 1 hr), and lesser increases to 168 and 195% of baseline during the late phase (1.5 to 4 h). These changes were associated with mild hypoxemia, marked leukopenia, and marked increases in plasma TxB2, 6-keto-PgF1 alpha and PgF2 alpha. The FPL-57231 completely blocked the endotoxin-induced changes in PVR, RL, and PaO2 during both phases without preventing the increases in TxB2; however, it partly attenuated the increases in 6-keto-PgF1 alpha and enhanced the generation of PgF2 alpha. Indomethacin, which blocked the endotoxin-induced increases in TxB2, 6-keto-PgF1 alpha, PgF2 alpha, and RL, only partly blocked the increase in PVR during the early phase, followed by an exaggerated increase of PVR during the late phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098147 TI - Effects of endotoxin and tannin isolated from cotton bracts on the airway epithelium. AB - The effects of increasing concentrations of tannin isolated from cotton bracts and endotoxin prepared from Enterobacter agglomerans on the electrophysiologic and ion transport properties of the canine tracheal epithelium mounted in Ussing chambers were examined. Results were compared with those obtained using cotton bracts extract (CBE). Tannin concentrations in the isolated tannin and in the cotton bracts were analyzed spectrophotometrically. When added to the mucosal bathing solution, tannin produced a significant decrease in transepithelial potential difference and short-circuit current (lsc) with a maximal response at 25 microliter. The decrease in lsc was accounted for entirely by a decrease in net chloride secretion. The effects were reversible and specific for the mucosal bathing solution. In contrast to CBE, tannin had no effect on mannitol flux, suggesting no effect on the paracellular pathway. Endotoxin at a concentration of 10 micrograms/ml had no effect on the electrophysiologic properties of the canine trachea. We conclude that tannin in CBE is responsible for the decrease in lsc observed with aqueous extracts of CBE but is not responsible for the changes in the paracellular pathway. We also conclude that endotoxin alone has no effect on the airway epithelium. PMID- 3098148 TI - Enzyme-linked immunosorbent assay using Mycobacterium tuberculosis antigen 5 for the diagnosis of pulmonary tuberculosis in China. AB - Measurement of serum IgG antibody to Mycobacterium tuberculosis antigen 5 by enzyme-linked immunosorbent assay was evaluated as a serodiagnostic test for pulmonary tuberculosis in China. The test was 89% sensitive and 94 to 100% specific with high accuracies of prediction. Among 82 tuberculous patients, antibody titer was related to the extent of pulmonary disease. Among control subjects, false positive tests were encountered among 5 of 52 persons with other pulmonary disease and not among 30 healthy subjects. The characteristics of this test compare favorably with those reported for sputum smear examination. PMID- 3098149 TI - [Typhoid and paratyphoid fevers in childhood. Apropos of 210 cases]. AB - The authors reviewed 210 children with typhoid and paratyphoid fevers; 191 were infected with S. typhi, 13 with S. paratyphi A and 6 with S. paratyphi B. The proportion was higher in school children. Fever, headache, tongue furred, stupor, and hepatomegaly were the most important clinical findings. Salmonella was cultured from the blood of 42% patients, the Widal reaction was negative only in one case, and faeces culture was positive in 25%. All patients received chloramphenicol. PMID- 3098150 TI - Psoriasis, gamma-interferon, and the acquired immunodeficiency syndrome. PMID- 3098151 TI - High-dose busulfan and myoclonic epilepsy. PMID- 3098152 TI - A high-potency, single-donor cryoprecipitate of known factor VIII content dispensed in vials. AB - Current factor VIII products expose recipients to many donors and hence to a high risk of acquiring blood-borne infections. Plasma-exchange donation of cryoprecipitate can reduce donor exposure by repeatedly obtaining large yields of factor VIII from individual donors. In this study, donor factor VIII levels were stimulated with desmopressin before donation. Mean yield per donation increased from 1399 +/- 425 IU in controls to 3818 +/- 1350 IU in stimulated donations (p less than 0.001), and mean factor VIII concentration in the cryoprecipitate increased from 8.2 +/- 3 IU/mL to 24 +/- 12 IU/mL (p less than 0.001). A new packaging system dispenses assayed aliquots of stimulated cryoprecipitate in plastic vials. The direct cost of production for this material is $.065 per unit. The cryoprecipitate is hemostatically active and convenient to use, and the aggregate yields from sequential donations by stimulated persons are high enough to allow long-term, single-donor support of many adults with hemophilia. PMID- 3098153 TI - HLA-D/DR expression on epithelial cells: the finger on the trigger? AB - The findings we have described here show a clear association between epithelial HLA-D/DR expression and autoimmunity. Furthermore, the ability of class II+ thyrocytes to present both exogenous antigens and autoantigens indicates an active role for these HLA-D/DR molecules in autoimmune pathogenesis. IFN-gamma is capable of inducing HLA-D/DR expression by thyroid epithelium, but a number of observations suggest the involvement of other inducers as well. Overall, we conclude that epithelial class II expression very probably plays a key role in the propagation and also in possibly the initiation of autoimmune attack. This is in accord with the proposal of a more general relationship between inappropriate or excessive class II expression and pathogenesis. PMID- 3098154 TI - Therapy of autoimmune diseases with antibody to immune response gene products or to T-cell surface markers. PMID- 3098155 TI - Carbon dioxide laser resection of superficial oral carcinoma: indications, technique, and results. AB - A retrospective medical record review was done of 51 consecutive patients with 56 biopsy-proven squamous cell carcinomas of the oral cavity and oropharynx treated for cure by one of the authors (H.H.D.) using the carbon dioxide laser via microdirect pharyngoscopy. All 51 patients were followed for at least 3 years unless they died, and 27 were followed for 5 years. The tumors treated were superficial, accessible lesions without bone involvement or clinically apparent metastases. Eighteen patients had had irradiation or surgery at the same site, so were having salvage CO2 laser surgery. Indications and technique are discussed. Local recurrence and disease control rates were comparable to those of conventional local surgical excision at 3 and 5 years. Complication rate was low. Carbon dioxide laser resection with microscopic control is, we propose, an excellent modality for transoral excision of carefully selected lesions, and it offers increased precision, better visualization, minimal bleeding, and decreased postoperative morbidity compared to other surgical techniques. PMID- 3098156 TI - Lymphangiomas of the larynx in infants and children. A survey of pediatric lymphangioma. AB - Lymphangiomas are uncommon benign congenital lymphatic tumors of childhood. They are found in all parts of the body structure, but rarely occur in the larynx. This paper reviews charts of 160 patients with cystic hygroma (lymphangiomata) of whom ten had extensive involvement of the larynx. A benign but nevertheless challenging tumor, its treatment demands the patience and skill of the surgeon. The lesion is more common in the white patient, and 40% appear in the newborn. Fifty percent present by the end of the first year of life, and 75% by the end of the second. The onset is uncommon in the older child and a rare occurrence in the adult. The treatment of lymphangiomata is surgical excision, and is more difficult when in the larynx. Laser surgery has been most helpful when the lesion is in the laryngeal complex. Considering the extreme difficulties which lymphangioma present to the child and to the physician, the ultimate results of all forms of conservative surgical therapy can be rewarding. Excessive or radical surgery will not necessarily guarantee complete elimination of disease and may be harmful. PMID- 3098157 TI - Serum thyroid hormones and thyroid hormone binding proteins in patients with completed stroke. AB - Thirty euthyroid patients hospitalized for completed stroke had serum thyroxine, triiodothyronine, thyroxine-binding globulin and thyroxine-binding prealbumin levels significantly decreased (p less than 0.01 to p less than 0.001) compared with 70 age- and sex-matched healthy controls. Admission serum thyroxine levels gave the best correlation with mortality (T4 less than 65 nmol/l = 100% mortality; 65-77 nmol/l = 38%; 78-90 nmol/l = 9%; greater than 90 nmol/l = 0%). In general, during hospitalization a progressive decrease in serum concentrations of these parameters was observed in the 11 patients who subsequently died, while there was a progressive increase in the 19 survivors. However, the most sensitive index of clinical recovery appeared to be prealbumin, since a decrease in prealbumin levels was observed in all subjects who died, and an increase in prealbumin was found in all survivors. PMID- 3098158 TI - Genetic transmission of myoclonus epilepsy with ragged red fibers. PMID- 3098159 TI - [Synthesis and study of the properties of (3S-trans)-3-amino-4-methylmonobactamic acid]. AB - The process for production of (3S-trans)-3-amino-4-methylmonobactamic acid (3 AMMA) was studied. It included transformation of L-threonine into amide, protection and activation of the functional groups, cyclization of the resulting beta-mesyloxyacylsulfomate into azetidinone followed by removal of the protecting group. For estimation of the completeness of the process separate stages and their optimization chromatography and spectroscopy were used. Stability, optical activity and chromatographic mobility of 3-AMMA under various conditions were studied. It was shown that solutions of 3-AMMA were rather stable in weak acid and neutral media and degraded at pH greater than 9.0. Control of this process was provided by circular dichroism. PMID- 3098160 TI - [Screening of human and animal tissue cell cultures as potential producers of plasminogen activator]. AB - Twenty six normal cell cultures and 19 tumor cell cultures were subjected to screening for plasminogen activator (PA), a fibrinolytic enzyme. It was shown that the enzyme production depended on the nature, origin, type and species of the tissue culture. The primary cultures of the human and calf embryonic kidney cells, permanent cell lines and tumor cells possessed high PA activity. The suspension cell lines did not produce the PA. PMID- 3098161 TI - [Treatment of an infection due to the intraperitoneal inoculation of mice with Pseudomonas aeruginosa with tobramycin and hyperimmune Pseudomonas aeruginosa plasma used per se and in combination]. AB - Schemes for treating infections caused by intraperitoneal administration of P. aeruginosa to mice were tested. The animals were treated with tobramycin and hyperimmune pyocyanic plasma (HPP) used per se or in combination. In a dose of 5 mg/kg body weight tobramycin protected 72.9 per cent of the animals from death. HPP with a titer of the antipyocyanic antibodies of 1:320-1:160 had a stable 100 per cent protective effect on the infected animals. However, no complete elimination of P. aeruginosa from the host was observed. The combined use of tobramycin and HPP LD50 protected 97.23 per cent of the mice from lethal infection, the drugs being titrated for their separate use. The combined administration of tobramycin and HPP in treatment of mice with acute infection due to P. aeruginosa was more efficient than their use alone. PMID- 3098162 TI - Effect of clavulanic acid on the activity of ticarcillin against Pseudomonas aeruginosa. AB - We studied the ability of clavulanic acid (CA) to induce beta-lactamase in Pseudomonas aeruginosa isolates and what effect this might have on the susceptibilities to beta-lactam agents. We first used a disk approximation method to test 4 laboratory and 16 clinical P. aeruginosa isolates against antipseudomonal beta-lactam agents for truncation by CA and found this to be very common. All antimicrobial compounds except imipenem demonstrated truncation in the vicinity of CA. We also evaluated the extent to which chromosomal beta lactamase is induced by CA and found this to occur to some degree in most isolates and to be dependent on the concentration of CA. Finally, we performed time kill curves on these isolates to compare bacterial growth in ticarcillin alone with growth in ticarcillin-CA (the CA at 2 or 4 micrograms/ml). We found that CA at this concentration has neither an antagonistic nor a synergistic antibacterial effect in combination with ticarcillin. PMID- 3098163 TI - In vitro activity of difloxacin hydrochloride (A-56619), A-56620, and cefixime (CL 284,635; FK 027) against selected genital pathogens. AB - Management of sexually transmitted diseases is facilitated by having antimicrobial agents with activity against all of the major genital pathogens. Newer quinolones show promise of being active against Neisseria gonorrhoeae and Chlamydia trachomatis. Two quinolones, difloxacin (A-56619) and A-56620, and an oral cephalosporin, cefixime (CL 284,635; FK 027), were evaluated in vitro. All three were highly active against 400 isolates of N. gonorrhoeae, including penicillinase-producing N. gonorrhoeae, N. gonorrhoeae with chromosomally mediated resistance, and isolates with penicillin MICs of less than 1 microgram/ml. Susceptibilities to one antimicrobial agent were usually strongly correlated with susceptibilities to the other antimicrobial agents evaluated, but isolates with increasing resistance to beta-lactams were least likely to show increasing resistance to quinolones. Difloxacin and, to a lesser extent, A-56620 were active against all 10 strains of C. trachomatis, and both had moderate activity against over 200 strains of Gardnerella vaginalis. Based on in vitro activity, difloxacin and A-56620 merit in vivo assessment for management of both C. trachomatis and N. gonorrhoeae infections, and cefixime shows considerable promise for treatment of N. gonorrhoeae infections. PMID- 3098164 TI - The apparent oxidation of NADH by whole cells of the methylotrophic bacterium Methylophilus methylotrophus. A cautionary tale. AB - Previous reports that whole cells of Methylophilus methylotrophus oxidase exogenous NADH have been investigated. Essentially identical rates of oxygen consumption were observed following the addition of methanol or NADH to whole cells. Both activities were inhibited by EDTA and hydroxylamine, but not by HQNO, and exhibited similar pH optima. Analyses of the reaction stoichiometry with NADH as substrate showed that the expected amount of oxygen was consumed, but also revealed acidification (instead of alkalinisation) and no oxidation of NADH. Further studies showed that commercial NADH is contaminated with ethanol which is oxidised to acetic acid by the low specificity methanol oxidase system present in this organism. The oxidation of exogenous NADH by whole cells of M. methylotrophus reported previously is therefore spurious. PMID- 3098165 TI - Relationship of formate to growth and methanogenesis by Methanococcus thermolithotrophicus. AB - Methanococcus thermolithotrophicus is a methanogenic archaebacterium that can use either H2 or formate as its source of electrons for reduction of CO2 to methane. Growth and suspended-whole-cell experiments show that H2 plus CO2 methanogenesis was constitutive, while formate methanogenesis required adaptation time; selenium was necessary for formate utilization. Cells grown on formate had 20 to 100 times higher methanogenesis rates on formate than cells grown on H2-CO2 and transferred into formate medium. Enzyme assays with crude extracts and with F420 or methyl viologen as the electron acceptor revealed that hydrogenase was constitutive, while formate dehydrogenase was regulated. Cells grown on formate had 10 to 70 times higher formate dehydrogenase activity than cells grown on H2-CO2 with Se present in the medium; when no Se was added to H2-CO2 cultures, even lower activities were observed. Adaptation to and growth on formate were pH dependent, with an optimal pH for both about one pH unit above that optimal for H2-CO2 (pH 5.8 to 6.5). When cells were grown on H2-CO2 in the presence of formate, formate (greater than or equal to 50 mM) inhibited both growth and methanogenesis at pH 5.8 to 6.2, but not at pH greater than 6.6. Both acetate and propionate produced similar inhibition. Formate inhibition was also observed in Methanospirillum hungatei. PMID- 3098166 TI - Toxicity of paraquat to microorganisms. AB - The biochemical response of the microorganisms Lipomyces starkeyi (Lod & Rij), Escherichia coli K-12 W3110, Bacillus subtilis 168 (Marburg) and Pseudomonas sp. strain TTO1 to the presence of growth-inhibitory concentrations of paraquat was studied. Paraquat was added to each culture at a concentration previously determined to reduce the culture growth rate by up to 50%. The changes in activity of a number of enzymes previously shown to be associated with the defense of the mammalian system against the action of paraquat were studied. While the response of E. coli was in agreement with that found in other studies of this microorganism and supports a commonly accepted mechanism for paraquat toxicity, the results obtained with L. starkeyi, B. subtilis, and Pseudomonas sp. strain TTO1 suggest that other mechanisms exist for protection against the toxicity of paraquat. PMID- 3098167 TI - Color mutants of Aspergillus flavus and Aspergillus parasiticus in a study of preharvest invasion of peanuts. AB - A comparison of the invasion of flowers, aerial pegs, and kernels by wild-type and mutant strains of Aspergillus flavus or A. parasiticus along with aflatoxin analyses of kernels from different drought treatments have supported the hypothesis that preharvest contamination with aflatoxin originates mainly from the soil. Evidence in support of soil invasion as opposed to aerial invasion was the following. A greater percentage of invasion of kernels rather than flower or aerial pegs by either wild-type A. flavus or mutants. Significant invasion by an A. parasiticus color mutant occurred only in peanuts from soil supplemented with the mutant, whereas adjacent plants in close proximity but in untreated soil were only invaded by wild-type A. flavus or A. parasiticus. Aflatoxin data from drought-stressed, visibly undamaged peanut kernels showed that samples from soil not supplemented with a mutant strain contained a preponderance of aflatoxin B's (from wild-type A. flavus) whereas adjacent samples from mutant-supplemented soil contained a preponderance of B's plus G's (from wild-type and mutant A. parasiticus). Preliminary data from two air samplings showed an absence of propagules of A. flavus or A. parasiticus in air around the experimental facility. PMID- 3098168 TI - Multiple antibiotics produced by Pseudomonas fluorescens HV37a and their differential regulation by glucose. AB - Pseudomonas fluorescens HV37a inhibited growth of the fungus Pythium ultimum on potato dextrose agar (PDA). An antibiotic activity produced under these conditions was fractionated and partially characterized. Extracts prepared from the PDA on which HV37a was grown revealed a single peak of antibiotic activity on thin-layer chromatograms. Similar extracts were prepared from mutants of HV37a. Their analysis indicated that the antibiotic observed in thin-layer chromatograms was responsible for fungal inhibition observed on PDA. The production of the PDA antibiotic required the presence of glucose, whereas two other antibiotic activities were produced only on potato agar without added glucose. Two mutants (denoted AfuIa and AfuIb) previously characterized as deficient in fungal inhibition on PDA showed altered regulation of the production of all three antibiotics in response to glucose. These mutants were also deficient in glucose dehydrogenase. Mutants isolated as deficient in glucose dehydrogenase were also deficient in fungal inhibition and were grouped into two classes on the basis of complementation analysis with an AfuI cosmid. Glucose regulation of antibiotic biosynthesis therefore involves at least two components and requires glucose dehydrogenase. PMID- 3098169 TI - DNA hybridization probe for the Pseudomonas fluorescens group. AB - Plasmid pHF360 was constructed from cloned rRNA genes (rDNA) of Pseudomonas aeruginosa and used as hybridization probe for the Pseudomonas fluorescens group. The probe was tested by dot and in situ colony hybridizations to chromosomal DNAs from a wide variety of organisms. pHF360 DNA hybridized exclusively to chromosomal DNAs from bacteria representing the P. fluorescens group and separated them clearly from all other bacteria tested in the present study. Determination of the nucleotide sequence of the cloned DNA showed that it is a fragment from a 23S rRNA gene of P. aeruginosa. It was compared with the published 23S RNA sequence from Escherichia coli. PMID- 3098170 TI - Heat resistance of bacterial spores correlated with protoplast dehydration, mineralization, and thermal adaptation. AB - Twenty-eight types of lysozyme-sensitive spores among seven Bacillus species representative of thermophiles, mesophiles, and psychrophiles were obtained spanning a 3,000-fold range in moist-heat resistance. The resistance within species was altered by demineralization of the native spores to protonated spores and remineralization of the protonated spores to calcified spores and by thermal adaptation at maximum, optimum, and minimum sporulation temperatures. Protoplast wet densities, and thereby protoplast water contents, were obtained by buoyant density sedimentation in Nycodenz gradients (Nyegaard and Co., Oslo, Norway). Increases in mineralization and thermal adaptation caused reductions in protoplast water content between limits of ca. 57 and 28% (wet weight basis), and thereby correlated with increases in sporal heat resistance. Above and below these limits, however, increases in mineralization and thermal adaptation correlated with increases in sporal resistance independently of unchanged protoplast water contents. All three factors evidently contributed to and were necessary for heat resistance of the spores, but dehydration predominated. PMID- 3098171 TI - Nature and reactivity of staphylococcal enterotoxin A monoclonal antibodies. AB - Monoclonal antibodies from four clones (C5, C3, B2II, and B2I) directed against staphylococcal enterotoxin A were tested by the indirect enzyme-linked immunosorbent assay and double-gel immunodiffusion (micro-Ouchterlony) assay for the nature of heavy and light chain types. The reactivities of monoclonal antibodies were also tested by indirect enzyme-linked immunosorbent assay with various levels of purified staphylococcal enterotoxin A and various levels (dilutions) of monoclonal antibodies and saturation analysis-competitive indirect enzyme-linked immunosorbent assay. The heavy-chain isotype of monoclonal antibodies was found to be an unspecified subclass of immunoglobulin G1, and the light chain was the kappa type. Monoclonal antibodies from all of the clones exhibited high reactivity and nearly the same affinity to staphylococcal enterotoxin A in saturation analysis-competitive enzyme-linked immunosorbent assay. Purified immunoglobulin G from B2I yielded very high absorbance (1.2) at 405 nm with 1 ng of staphylococcal enterotoxin A as the coating antigen in the enzyme-linked immunosorbent assay. Monoclonal antibodies from B2I also neutralized the biological activity of staphylococcal enterotoxin A when tested by the kitten bioassay. PMID- 3098172 TI - Thermal resistance of intracellular Listeria monocytogenes cells suspended in raw bovine milk. AB - The thermal resistance of Listeria monocytogenes associated with a milk-borne outbreak of listeriosis was determined in parallel experiments by using freely suspended bacteria and bacteria internalized by phagocytes. The latter inoculum was generated by an in vitro phagocytosis reaction with immune-antigen-elicited murine peritoneal phagocytes. The heat suspension medium was raw whole bovine milk. Both suspensions were heated at temperatures ranging from 52.2 to 71.7 degrees C for various periods of time. Mean D values for each temperature and condition of heated suspension revealed no significant differences. The extrapolated D71.7 degrees C (161 degrees F) value for bacteria internalized by phagocytes was 1.9 s. Combined tube and slug-flow heat exchanger results yielded an estimated D71.7 degrees C value of 1.6 s for freely suspended bacteria. The intracellular position did not protect L. monocytogenes from thermal inactivation. PMID- 3098174 TI - Cadmium-mediated inhibition of testicular heme oxygenase activity: the role of NADPH-cytochrome c (P-450) reductase. AB - The concerted activity of two microsomal enzymes, heme oxygenase and NADPH cytochrome c (P-450) reductase, is required for isomer-specific oxidation of heme molecule; heme oxygenase is commonly believed to be rate limiting in this activity. In this report, we provide evidence strongly suggesting the rate limiting role of the reductase in oxidation of heme molecule in rat testis. In the testis and the liver of rats treated with Cd (20 mumol/kg, sc, 24 h) heme oxygenase activity, assessed by the formation of bilirubin, was decreased by 50% and increased by 7-fold, respectively. In these animals, the reductase activity was decreased by nearly 75% in the testis, but remained unchanged in the liver. Similarly, the reductase activity in the liver was not altered when heme oxygenase activity was increased by 20-fold in response to bromobenzene treatment. Addition of purified testicular reductase preparation (purified over 4000-fold), or hepatic reductase, to the testicular microsomes of Cd-treated rats obliterated the Cd-mediated inhibition of heme oxygenase activity. The chromatographic separation of heme oxygenase and the reductase of the testicular microsomal fractions revealed that the reductase activity was markedly decreased (75%) while the heme oxygenase activity, when assessed in the presence of exogenous reductase, was not affected by in vivo Cd treatment. In vitro, the membrane-bound reductase preparation obtained from the testis was more sensitive to the inhibitory effect of Cd than the liver preparation. However, the purified reductase preparations from the testis and the liver exhibited a similar degree of sensitivity to Cd. Based on the molar ratio of heme oxygenase to the reductase in the microsomal membranes of the liver and the testis it appeared that the testicular heme oxygenase, which is predominantly HO-2 isoform, interacts with the reductase less effectively than HO-1; in the induced liver, heme oxygenase is predominantly the HO-1 isoform. It is suggested that due to the low abundance of NADPH-cytochrome c (P-450) reductase and the apparently lower affinity of the enzyme for HO-2, the reductase exerts a regulatory action on heme oxygenase activity in the testis. PMID- 3098173 TI - Mechanism of the glycine cleavage reaction: retention of C-2 hydrogens of glycine on the intermediate attached to H-protein and evidence for the inability of serine hydroxymethyltransferase to catalyze the glycine decarboxylation. AB - Glycine is converted to carbon dioxide and an intermediate attached to a lipoic acid group on H-protein in the P-protein-catalyzed partial reaction of the glycine cleavage reaction [K. Fujiwara and Y. Motokawa (1983) J. Biol. Chem. 258, 8156-8162]. The results presented in this paper indicate that the decarboxylation is not accompanied by the removal of a C-2 hydrogen atom of glycine and instead both C-2 hydrogens are transferred with the alpha carbon atom to the intermediate formed during the decarboxylation of glycine. The purified chicken liver cytosolic and mitochondrial serine hydroxymethyltransferase preparations could not catalyze the decarboxylation of glycine in the presence of either lipoic acid or H-protein. The decarboxylation activity of the serine hydroxymethyltransferase preparation purified from bovine liver by the method similar to that of L. R. Zieske and L. Davis [(1983) J. Biol. Chem. 258, 10355-10359] was completely inhibited by the antibody to P-protein, while the antibody had no effect on the activity of the phenylserine cleavage. Conversely, D-serine inhibited the activity of phenylserine cleavage but the activity of the decarboxylation of glycine was not affected by D-serine. Finally, the two activities were separated by the chromatography on hydroxylapatite. The results clearly demonstrate that serine hydroxymethyltransferase per se cannot catalyze the decarboxylation of glycine. PMID- 3098175 TI - Digitoxin metabolism by liver microsomal cytochrome P-450 and UDP glucuronosyltransferase and its role in the protection of rats from digitoxin toxicity by pregnenolone-16 alpha-carbonitrile. AB - The aim of the present study was to investigate whether the mechanism by which pregnenolone-16 alpha-carbonitrile (PCN) protects rats from digitoxin toxicity was dependent on the induction of liver microsomal cytochrome P-450p and/or the UDP-glucuronosyltransferase active toward digitoxigenin monodigitoxoside (UDP-GT dt1). Evidence is presented that suggests troleandomycin is a selective inhibitor of cytochrome P-450p in vivo, based on the pattern of inhibition observed when zoxazolamine paralysis time and hexobarbital sleeping time were measured in rats treated with different cytochrome P-450 inducers. A single dose of troleandomycin completely reversed the ability of PCN to protect rats from digitoxin toxicity, establishing the importance of cytochrome P-450p induction in the protective effect of PCN. The postpubertal decline in constitutive cytochrome P-450p levels in female but not male rats was paralleled by a female-specific, age-dependent decline in the rate of digitoxin sugar cleavage (i.e., digitoxosyl oxidation of digitoxin to 15'-dehydrodigitoxin and digitoxosyl cleavage to digitoxigenin bisdigitoxoside). This resulted in a marked sex difference in the rate of digitoxin sugar cleavage catalyzed by liver microsomes from mature rats (male/female approximately 6). However, no sex difference in digitoxin toxicity was observed in either immature or mature rats. In contrast to cytochrome P-450p, liver microsomal UDP-GT-dt1 activity increased dramatically with age in both male and female rats (mature/immature approximately 10). However, no age differences in digitoxin toxicity were observed in rats of either sex. The results indicate that cytochrome P-450p and UDP-GT-dt1 can be independently regulated in rat liver and that large changes in the constitutive levels of these microsomal enzymes have no effect on digitoxin toxicity. This suggests that the induction of cytochrome P-450p and UDP-GT-dt1 does not fully account for the mechanism by which PCN protects rats from digitoxin toxicity. PMID- 3098176 TI - Inhibition of CA V decreases glucose synthesis from pyruvate. AB - The carbonic anhydrase inhibitor acetazolamide reduces citrulline synthesis by intact guinea pig liver mitochondria and also inhibits mitochondrial carbonic anhydrase (CA V) and the more lipophilic carbonic anhydrase inhibitor ethoxzolamide reduces urea synthesis by intact guinea pig hepatocytes in parallel with its inhibition of total hepatocytic carbonic anhydrase activity. Intact hepatocytes from 48-h starved male guinea pig livers were incubated at 37 degrees C in Krebs-Henseleit with 95% O2/5% CO2 at pH 7.1 with 5 mM pyruvate, 5 mM lactate, 3 mM ornithine, 10 mM NH4Cl, 1 mM oleate; with these inclusions both urea and glucose synthesis start with HCO3- -requiring enzymes, carbamyl phosphate synthetase I and pyruvate carboxylase, respectively. Urea and glucose synthesis were inhibited in parallel by increasing concentrations of ethoxzolamide, estimated Ki for each approximately 0.1 mM. In other experiments hepatocytes were incubated at 37 degrees C in Krebs-Henseleit with 95% O2/5% CO2 at pH 7.1 with 10 mM glutamine, 1 mM oleate; with these inclusions glucose synthesis no longer starts with a HCO3- -requiring enzyme. Urea synthesis was inhibited by ethoxzolamide with an estimated Ki of 0.1 mM, but glucose synthesis was unaffected. Intact mitochondria were prepared from 48-h starved male guinea pig livers. Pyruvate carboxylase activity of intact mitochondria was determined in isotonic KCl-Hepes buffer, pH 7.4, 25 degrees C, with 7.5 mM pyruvate, 3 mM ATP, and 10 mM NaHCO3. Inclusion of ethoxzolamide resulted in reduction in the rate of pyruvate carboxylation in intact mitochondria, but not in disrupted mitochondria. It is concluded that carbonic anhydrase is functionally important for gluconeogenesis in the male guinea pig liver when there is a requirement for bicarbonate as substrate. PMID- 3098177 TI - r-Galactonolactone in experimental galactosemic animals. AB - An accumulation of galactose-1,4-lactone, an oxidation product of galactose, was observed in various tissues of galactosemic guinea pigs fed a 40% galactose diet for 6 weeks. In addition, an accumulation of the two galactose metabolites varied among organs. The highest content of the lactone was observed in the liver and the content of the lactone exceeded that of the reduced counterpart. The lens gave the highest galactitol content. In the serum the level of the lactone was very low. A trace amount of the lactone was detected in the kidney while it was mostly excreted into urine within 54 h upon withdrawal of the diet. On the other hand, in the animals kept on a high galactose diet for only 2 days, urinary lactone rapidly decreased. These observations indicated that a high galactose level in the circulation was associated with the production of the lactone in various tissues and that the accumulated lactone was released into the circulation very slowly and then excreted into the urine. Suppression of galactitol production by administration of an aldose reductase inhibitor resulted in the accumulation of the lactone in the lens, the testis, and the muscle, as well as in the circulation. The lactone thus produced was excreted exclusively into the urine. This observation indicates a close relationship between the oxidative and reductive metabolisms of galactose at a toxic level. PMID- 3098179 TI - Cationic form of beta-galactosidase in the germinating seeds of Vigna sinensis (Linn) Savi. AB - The cationic form of beta-galactosidase (EC 3.2.1.23) from the germinating seeds of Vigna sinensis has been separated from its other isoforms by DEAE-cellulose (DE-52) column chromatography and further purified by gel filtration and affinity chromatography. Polyacrylamide gel electrophoresis of the purified enzyme imparted a single protein band. The molecular mass of the enzyme as determined by Sephadex G-150 gel filtration is 58,800 Da. The optimum temperature and the optimum pH are 60 degrees C and 4.5, respectively. Most of the metal ions tested were inhibitory to the enzyme activity. The enzyme has Km for p-nitrophenyl beta D-galactoside and o-nitrophenyl beta-D-galactoside of 0.56 and 2.0 mM, respectively. The Ki values of galactose and lactose are 2.4 and 70.0 mM, respectively. The energy of activation of PNPG for the enzyme is 10.3 kcal/mol. PMID- 3098178 TI - Tunicamycin inhibits proteoglycan synthesis in rat ovarian granulosa cells in culture. AB - The effects of tunicamycin, an inhibitor of N-linked oligosaccharide biosynthesis, on the synthesis and turnover of proteoglycans were investigated in rat ovarian granulosa cell cultures. The synthesis of proteoglycans was inhibited (40% of the control at 1.6 micrograms/ml tunicamycin) disproportionately to that of general protein synthesis measured by [3H]serine incorporation (80% of control). Proteoglycans synthesized in the presence of tunicamycin lacked N linked oligosaccharides but contained apparently normal O-linked oligosaccharides. The dermatan sulfate and heparan sulfate chains of the proteoglycans had the same hydrodynamic size as control when analyzed by Sepharose 6B chromatography. However, the disulfated disaccharide content of the dermatan sulfate chains was reduced by tunicamycin in a dose-dependent manner, implying that the N-linked oligosaccharides may be involved in the function of a sulfotransferase which is responsible for sulfation of the iduronic acid residues. When [35S]sulfate and [3H]glucosamine were used as labeling precursors, the ratio of 35S/3H in chondroitin 4-sulfate was reduced to approximately 50% of the control by tunicamycin, indicating that the drug reduced the supply of endogenous sugar to the UDP-N-acetylhexosamine pool. Neither transport of proteoglycans from Golgi to the cell surface nor their turnover from the cell surface (release into the medium, or internalization and subsequent intracellular degradation) was affected by the drug. Addition of mannose 6-phosphate to the culture medium did not alter the proteoglycan turnover. When granulosa cells were treated with cycloheximide, completion of proteoglycan diminished with a t1/2 of approximately 12 min, indicating the time required for depleting the core protein precursor pool. The glycosaminoglycan synthesizing capacity measured by the addition of p-nitrophenyl-beta-xyloside, however, lasted longer (t1/2 of approximately 40 min). Tunicamycin decreased the core protein precursor pool size in parallel to decreased proteoglycan synthesis, both of which were significantly greater than the inhibition of general protein synthesis. This suggests two possibilities: tunicamycin specifically inhibited the synthesis of proteoglycan core protein, or more likely a proportion of the synthesized core protein precursor (approximately 50%) did not become accessible for post-translational modifications, and was possibly routed for premature degradation. PMID- 3098180 TI - [Activation of oncogenes by chemical modification with carcinogens]. AB - This article reviews the chemical modification of DNA (mainly proto-Ha-ras sequence) which causes mutation and induction of transforming activity. An initial chemical event caused by chemical carcinogens is modification of DNA with metabolically activated carcinogens. The chemical modification of DNA is thought to result in activation of oncogenes by mutation or reconstruction. The activated transforming oncogenes (mainly of the ras family, by point mutation) have been found in tumors induced by diverse carcinogens in vivo (reviewed briefly). Recently, results establishing that chemical modification of proto-oncogenes with carcinogens, such as benz (a) pyrene, acetylaminofluorene, Glu-P-1, 4NQO, and aflatoxin B1, induces transforming activity of the gene when transfected into NIH3T3 cells have been reported. The mechanism of activation of proto-Ha-ras by chemical modification has been investigated by RFLP (restriction fragment length polymorphism) assay and/or Southern blot analysis using synthetic oligonucleotides. Point mutations at codon 12 or 61 have been found. The correlation between the established chemistry of chemical modification of DNA with diverse carcinogens and activation of proto-oncogenes is discussed. PMID- 3098181 TI - [The active structure of tumor promoters]. AB - Diterpene esters containing 12-0-tetradecanoylphorbol-13-acetate (TPA) and the alkaloid teleocidins are structurally unrelated natural products that exhibit similar potent skin tumor-promoting activity. These promoters are classified as TPA-type promoters because they bind equally to the phorbol ester receptor. TPA can be considered as an amphiphilic compound, with a hydrophilic domain spanning the C-3 to C-20 region of the molecule and a lipophilic domain consisting of the acyl substituents on C-12 and C-13. Teleocidins can also be considered as amphiphilic compounds, with the hydrophilic domain spanning the C-11 to C-14 region of the molecule and the lipophilic domain consisting of the alkyl substituents on C-6, C-7 and C-12. Teleocidins exist in two conformational states, the TWIST form and the SOFA form, in solution. From the ratio of the two conformations in solution, the free-energy difference between them was calculated to be 0-1.5 kcal/mol. Therefore a possible role of one of the two conformations should be considered in the modeling of receptor mapping. Computer modeling of the SOFA form of teleocidins and TPA showed a marked similarity with regards to the hydrogen bonding sites of the hydrophilic substituents. In this case, good superposition of the lipophilic regions of both types of compounds was obtained. PMID- 3098182 TI - [Experimental study of UFT in prostatic carcinoma (DU-145) in nude mice]. AB - We evaluated the anticancer effect of UFT, which is composed of 1-(2 tetrahydrofuryl)-5-fluorouracil (Tegafur) and uracil in a molar ratio of 1:4, for prostatic carcinoma (DU-145) in nude mice, and the effect of 5-fluorouracil (5 FU) in vitro. Tumor growth of DU-145 in nude mice was inhibited in the group administered UFT (20 mg/kg), but was not in the Tegafur (100 mg/kg) group in comparison with the control group. The concentration of 5-FU in the tumor reached higher levels in the group administered UFT in comparison with the Tegafur group. Also, DU-145 cells were inhibited by about 70% in 4 gamma concentration of 5-FU compared with the control. These data suggest the clinical usefulness of UFT for prostatic carcinoma. PMID- 3098183 TI - [In vitro enhancement of cytotoxicity of human peripheral blood lymphocytes with recombinant interleukin 2 and an interferon mixture (alpha + beta + gamma) against human colon carcinoma cell line SW1116]. AB - The cytocidal effect of human peripheral blood lymphocytes (PBL's) enhanced by human recombinant interleukin 2 (IL-2) on human colon carcinoma cell line SW1116 was examined in vitro in the presence of plasma from patients with recurrence of colorectal carcinoma. In addition, human recombinant interferons alpha, beta, and gamma were combined to enhance this cytotoxicity of PBL's. Cytotoxicity of PBL's was enhanced by IL-2. Patients' plasma blocked the cytotoxicity of PBL's. Serially added IL-2 was able to maintain the enhanced cytotoxicity of PBL's in the presence of patients' plasma. The mixture of interferons (alpha + beta + gamma, or beta + gamma) directly killed target cells more efficiently than with single use of each interferon or other combinations of interferons. These mixtures of interferons (alpha + beta + gamma, or beta + gamma) also activated cytotoxicity of PBL's. The cytotoxicity of IL-2-activated PBL's was further enhanced by intermittent addition of the interferon mixture. PMID- 3098184 TI - [A case of relapsed gastric cancer treated successfully by chemotherapy--lung metastasis and relapsed cancer in the hepatic portal system]. AB - A case of relapsed gastric cancer postoperatively presenting obstructive jaundice due to metastases in the hepatic portal and periaortic lymph nodes and multiple lung metastases was given OK-432 continuously i.m. and UFT p.o., and then generally given cisplatin and massive doses of carboquone i.a. intermittently into the peritoneal cavity. The chemotherapy led to complete remission of the obstructive jaundice and disappearance of the metastases in the lungs and lymph nodes. PMID- 3098185 TI - Growth and childhood asthma. AB - Height and weight were measured every six months in a long term prospective study of 66 children with chronic perennial asthma for a mean 13.1 years. There was no evidence of growth retardation on entry into the study. Growth developed along normal lines in all 66 children until about 10 years, and in 35 of these children growth continued along normal lines throughout the whole period of follow up. Thirty children showed the physiological decelerating growth velocity pattern seen in children with delay in the onset of puberty, and one child had an early menarche. The tendency for delay in the onset of puberty was significant for both boys and girls and was noted to be independent of severity of asthma. Once puberty finally began in these children, complete catch up growth resulted in the attainment of the predicted adult height. Long term prophylactic inhalation of beclomethasone dipropionate in 26 children in a dosage up to 600 mcg/day before puberty and 400 mcg/day during puberty was shown not to affect growth. It is concluded that asthma had no direct influence on growth in height but was associated with delay in the onset of puberty. The pre-adolescent physiological deceleration of growth velocity that occurs in these children gives the impression of growth retardation. PMID- 3098186 TI - Serum antibodies to Pseudomonas aeruginosa in cystic fibrosis. AB - Serum IgG antibodies to Pseudomonas aeruginosa cell surface antigens were determined by enzyme linked immunosorbent assay. Titres in patients without cystic fibrosis were low (140-235). Those in patients with cystic fibrosis who were chronically infected by P. aeruginosa were very high (1100-20,500), while patients who grew the organism intermittently had lower titres (160-4400). Longitudinal studies showed that raised titres were observed at a very early stage of infection. High titres were associated with a poor clinical state, while low titres were associated with a better clinical state in both chronic and intermittently infected patients with cystic fibrosis. These results suggest that this test is a specific and sensitive measure of the severity and progress of the different stages of pulmonary infection by P. aeruginosa in patients with cystic fibrosis. PMID- 3098187 TI - Percutaneous insertion of central venous feeding catheters. PMID- 3098188 TI - Studies on the environmental fate of carbaryl as a function of pH. PMID- 3098189 TI - A congener analysis of polychlorinated biphenyls accumulating in rat pups after perinatal exposure. PMID- 3098190 TI - Transfer and distribution of accumulated (14C)polychlorinated biphenyls from maternal to fetal and suckling rats. PMID- 3098191 TI - LC50 test results in polychlorinated biphenyl-fed mink: age, season, and diet comparisons. PMID- 3098193 TI - Demonstration of antiglobulin activity in the synovial membrane of patients with rheumatoid arthritis and ankylosing spondylitis after pepsin treatment: real or artefact? AB - The results of immunofluorescence studies in nine cases of rheumatoid arthritis and nine cases of ankylosing spondylitis are presented. Antiglobulin activity was sought with fluorescein labelled, heat aggregated human IgG and rabbit immunoglobulin (indirect immunofluorescence). A similar degree of increased staining for rheumatoid factor activity was seen after pepsin digestion in all cases of rheumatoid arthritis and three of the ankylosing spondylitic cases. This staining for rheumatoid factor could also be shown in control tissue after pepsin digestion, suggesting that the enhanced staining was an artefact. PMID- 3098192 TI - Antinuclear antibodies in the relatives and spouses of patients with systemic sclerosis. AB - The families of 65 patients with systemic sclerosis were examined clinically and serum samples from each subject were tested for antinuclear antibodies (ANA) by immunofluorescence on HEp2 cells and for precipitating antibodies to soluble cellular antigens including Scl-70. Of 217 blood relatives, 58 (27%) had ANA (42 speckled, 13 nucleolar, one centromere, two homogeneous); 22 (10%) had precipitins, one anti-Scl-70, one anti-PM-Scl, one anti-nRNP, two anti-Ro(SSA), the remainder unidentified). Family members tended to share ANA patterns. Of 38 spouses, nine (24%) had ANA (all speckled) and two showed unidentified precipitins. This compares with an incidence of ANA and precipitins in a control population of 8% and 1% respectively. Antibodies were more common in female than male relatives (particularly in mothers and sisters of probands). Twenty one of the 58 family members with ANA had clinical features of connective tissue disease; the remainder were asymptomatic. The presence of genetic factors influencing autoimmunity is suggested by the incidence of autoantibodies in first degree relatives. Similar observations in spouses, however, indicate that environmental factors may also have a role in these immune abnormalities. PMID- 3098194 TI - Early and late changes in sulphydryl group and copper protein concentrations and activities during drug treatment with aurothiomalate and auranofin. AB - Superoxide dismutase activity (SOD), plasma and lysate thiol concentrations (PSH and LSH), and caeruloplasmin oxidase activity (CP) reflect the underlying reduction-oxidation imbalance associated with rheumatoid arthritis (RA), and are believed to be involved in the protection of the cell against free radical activity. The early and late changes in these parameters have been observed and compared with standard clinical and biochemical assessments of disease activity in 90 patients with active RA, randomly assigned to receive either sodium aurothiomalate, auranofin, or auranofin placebo. An index based on clinical criteria was used to identify patients as responders or non-responders after 24 weeks of therapy. In the first six weeks of treatment a change in SOD activity and LSH concentration in a direction away from controls was followed by a return towards control levels in responders only. This suggests that in RA evidence of clinical improvement induced by gold drugs is preceded by an initial biochemical response in an inflammatory direction. The extracellular parameters PSH and CP did not show the same early response, but PSH levels in responders showed a slower change towards normal values, though at no time were values obtained that might suggest a complete remission. Thus the intracellular parameters appear to reflect an early effect of the drugs on cells which may possibly be of use in predicting the outcome of therapy, whereas the extracellular parameters provide confirmatory evidence for an eventual improvement. PMID- 3098195 TI - Growth of monosodium urate monohydrate crystals: effect of cartilage and synovial fluid components on in vitro growth rates. AB - The effects of cartilage and synovial fluid components such as proteoglycans, chondroitin sulphate, hyaluronic acid, phospholipids, and albumin on the growth kinetics of monosodium urate monohydrate (MSUM) crystals were investigated. MSUM seed crystals were added to supersaturated sodium urate solutions, and the rate of decrease in the concentration of growth medium was used as a measure of the growth rate. A second order dependence of growth rate on supersaturation was found, and growth rate constants were determined with an integrated form of the growth equation. The additives, hyaluronic acid, proteoglycan monomer and aggregate, and phosphatidylserine, had no significant effect on the growth rate constant. Chondroitin sulphate and phosphatidylcholine increased the growth rate constant, possibly by promoting further nucleation in the growth medium. Albumin significantly inhibited MSUM crystallisation. The possible implications of these findings on in vivo MSUM crystallisation are discussed. PMID- 3098196 TI - Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. IV. Increased numbers and activation of Facb-R+ cells after immunisation of healthy individuals. AB - Mononuclear cells expressing Fc gamma receptors that form Facb rosettes are increased in the peripheral blood of patients with rheumatoid arthritis compared with controls. Healthy individuals with a positive skin response to tuberculin showed a marked increase in numbers of circulating Facb-R+ cells three days after challenge, returning to baseline after seven days. No response was observed in subjects showing a negative skin test. A similar increase in Facb-R+ cell numbers was measured after intramuscular injection of another specific antigen, tetanus toxoid. In addition to this enhancement of Facb-R+ cell numbers, evidence has been obtained that these cells are in an activated state postimmunisation as judged by acquisition of low density and increased expression of class II MHC antigens. Apparently identical changes in Facb-R+ cell numbers and activation may be induced in vitro either by culturing sensitised mononuclear cells with specific antigen for three days or by an overnight incubation of normal cells with gamma-interferon (gamma-IFN). By analogy, therefore, the increased numbers of Facb-R+ cells in patients with rheumatoid arthritis are probably induced by gamma-interferon generated as part of an antigen driven immune response. In this context it is interesting that patients with Felty's syndrome, in whom neutropenia increases susceptibility to infections leading to the possibility of further stimulation of the immune system by micro-organisms, have particularly high levels of circulating Facb-R+ cells. PMID- 3098197 TI - Thermic effect and substrate oxidation in response to intravenous nutrition in cancer patients who lose weight. AB - This study examined oxidative metabolism and thermogenesis in the acute response to controlled intravenous nutrition in seven cancer patients who lost weight. Six weight-losing and malnourished patients without cancer served as controls. Indirect calorimetry was used and measurements of arterial concentrations of various substrates, metabolic end products, and insulin were performed. Resting energy expenditure (REE) was measured after an overnight fast. The resting energy need was calculated for each patient according to REE. The nutrition program consisted of glucose and lipids (Intralipid KabiVitrum AB, Stockholm, Sweden) each as 50% of nonprotein calories and amino acids (6.9 mg N/kcal). These substrates were infused simultaneously at rates equivalent to one, two, and three times REE, over periods of 6.5 hours on 3 consecutive days after a 12-hour fast. Arterial substrate levels and energy expenditure were measured between 6 and 6.5 hours after the start of the infusion. The cancer patients had well-recognized metabolic changes in the fasted state, such as elevated plasma levels of glycerol, triglycerides, free fatty acids, and lactate, and higher energy expenditure than predicted. The cancer patients responded to strictly defined substrate challenge in a similar way as the malnourished patients without cancer. Whole body oxidative capacity and the proportion of infused glucose and lipids that were oxidized at different levels of infusion rates were not decreased in cancer patients compared with control patients. Similar arterial substrate concentrations among the groups during infusions argues for a maintained plasma clearance of the substrate in the cancer patients. This study supports the suggestion that cachectic cancer patients can generate and conserve energy normally in response to intravenous nutrition. This refers to cancer patients with a history of weight loss up to 15% of their normal body weight. Therefore, weight loss due to altered tumor-host metabolism in cancer patients is of quantitative importance in the fasted state rather than in the fed state. PMID- 3098198 TI - Glucose, fatty acid, and urea kinetics in patients with severe pancreatitis. The response to substrate infusion and total parenteral nutrition. AB - Rates of glucose turnover and oxidation in normal volunteers (N = 16) and in severely ill patients with pancreatitis (N = 9) were isotopically determined. Glucose turnover was determined using primed constant infusions of either 6-3H glucose or 6-d2-glucose, and glucose oxidation with either U-14C-glucose or U-13C glucose after appropriate priming of the bicarbonate pool. Urea kinetics were determined using primed constant infusions of either (15N2)-urea or U-14C-urea, whereas free fatty acid (FFA) kinetics were determined by the constant infusion of 1,2-13C palmitate. Basal rates of glucose production and plasma glucose clearance were significantly higher in the patients than in the volunteers. During glucose infusion (4 mg/kg/min) endogenous glucose production was virtually totally suppressed in the volunteers (94 +/- 4%). There was significantly less suppression in the patients, however (44 +/- 1%). In addition, the percentage of available glucose oxidized (i.e., percentage of uptake oxidized) was significantly less in the patients than in the volunteers. The basal rate of urea production was significantly higher in the patients; however, in both patients and volunteers, glucose infusion resulted in a significant decrease. The rate of FFA turnover was similar in the patients and volunteers, and the patients and volunteers were equally sensitive to the suppressive effects of glucose infusion. When the patients were studied during total parenteral nutrition (TPN), there was no further suppression of endogenous glucose turnover than that seen during 2 hours of glucose infusion, and the mean rate of urea turnover measured during TPN (7.0 +/- 1.9 mumol/kg/min) was also not significantly different than the value determined during glucose infusion (8.9 +/- 1.8 mumol/kg/min). It was concluded from these studies that patients with pancreatitis are metabolically similar to septic patients, have an impairment in their ability to oxidize infused glucose when compared with normal volunteers, have an elevated rate of net protein catabolism, and have FFA kinetics similar to those seen in normal humans. PMID- 3098199 TI - Determinants of cardiac failure after coronary bypass surgery within 30 days of acute myocardial infarction. AB - Timing of coronary artery bypass grafting after acute myocardial infarction (MI) is controversial, especially if myocardial function is depressed. Early coronary artery bypass grafting may result in reperfusion injury causing cardiac failure. Delay, however, may risk a second ischemic event. This study was performed to determine if four preoperative factors--time after MI, ejection fraction, ischemia (need for intravenous administration of nitroglycerin), and failure (need for inotropic support)--independently predict postoperative cardiac failure. Postoperative failure was defined as the need for inotropic support or intraaortic balloon pumping. The study group consisted of 145 patients who underwent isolated coronary artery bypass grafting between January, 1980, and July, 1985, within 4 weeks of an acute MI. Postoperatively 38 patients (26%) had cardiac failure. Five patients, all of whom had postoperative cardiac failure, died. Univariate and stepwise logistic regression analyses showed preoperative failure (p = .0001), ejection fraction less than 45% (p = .002), and preoperative ischemia (p = .02) were predictors of postoperative cardiac failure. Time after MI was not found to be an independent predictor (p = .96). We conclude that if ischemia or threatening coronary anatomy is present early after MI and clinical improvement is not occurring, operative intervention should be strongly considered at that time, as it does not appear that delay itself reduces the risk of cardiac failure and may risk a second ischemic event. PMID- 3098200 TI - Testicular function in adult rats treated with the alkylating agent chlorambucil. AB - The effects of multiple treatments with the alkylating agent chlorambucil on testicular function in the adult Wistar rat were evaluated. Weekly treatment with doses of 2.5, 5, or 10 mg/kg produced no effect either on spermatogenesis or Leydig cell function. In contrast, doses of 8 or 10 mg/kg administered twice weekly induced damage to both spermatogenesis and probably the Leydig cells. A dose-dependent decrease in spermatogonial stem-cell survival was observed with these two regimens, as assessed by counts of repopulating tubule cross sections. Although serum testosterone remained unchanged, possible Leydig cell damage was indicated by an approximate twofold increase in serum LH following treatment with either 8 or 10 mg/kg of chlorambucil twice weekly. The present results demonstrate that multiple treatments with cytotoxic drugs can be used to model the testicular damage observed in man. PMID- 3098201 TI - Alginate biosynthesis by Pseudomonas aeruginosa: effect of arsenite and other metabolic inhibitors. AB - Biosynthesis of alginic acid in presence of metabolic inhibitors by resting cells of mucoid Pseudomonas aeruginosa was studied. Among the inhibitors tested, arsenite exhibited very interesting results, while the others showed no remarkable effect. Firstly, arsenite stopped alginate production from all the substrates during initial hours of incubation; secondly, degradation of newly synthesized alginates to smaller molecular weight fragments took place if it was added after a few hours of incubation with the substrate; and thirdly, uncontrolled synthesis of alginate started after several hours of inhibition. Presence of arsenite was needed for the initial inhibitory phase of alginate synthesis; but once the cells were capable of synthesizing alginate after initial hours of inhibition, arsenite may be omitted from the medium. PMID- 3098202 TI - [Lafora disease. Morphopathologic analysis of its hypothetical relation to amylopectinosis apropos of the study of 3 cases]. PMID- 3098203 TI - [Topical and systemic antimicrobial agents in the treatment of gingivitis and chronic periodontitis]. PMID- 3098204 TI - [Morphology of root anomalies]. PMID- 3098205 TI - [Anatomical location of oral cancer. Epidemiological study of a sample of 782 cases of epidermoid carcinoma]. PMID- 3098206 TI - Critical evaluation of the ADCC test. AB - The activity of monocytes in the ADCC test against human red blood cells sensitized with anti-Rh antibodies is unquestionable, however, a participation of lymphocytes in this reaction is still controversial. The aim of this paper was to test the cytotoxic activity of monocytes and lymphocytes isolated from human peripheral blood against erythrocytes coated with anti-C + D antibodies of Rh system. Due to some individual changes in the activity of mononuclears observed in the ADCC test, it was of interest to test how this activity changes with time, in individual healthy subjects. Both types of mononuclears were observed to damage the sensitized non-treated as well as papain-treated red cells. The cytotoxic activity of these cells, however, showed substantial deviation in the same person. PMID- 3098207 TI - Polar solvents in the chemoprevention of dimethylbenzanthracene-induced rat mammary cancer. AB - Differentiating agents have been used experimentally and clinically as an adjuvant in the treatment of cancer, but their role in chemoprevention is limited. We used 5% dimethylsulfoxide (DMSO), 1% and 4% methylsulfonylmethane (MSM), 0.3% N-methylformamide (NMF), and retinol acetate (RA) in the chemoprevention of rat mammary breast cancer. One hundred fifty 42-day-old Sprague-Dawley rats were randomized into six groups (control, RA, DMSO, 1% MSM, NMF, and 4% MSM) and received chemopreventive agents along with standard rat chow ad libitum. Eight days later, 15 mg of 7,12-dimethylbenzanthracene was given by oral gastric intubation. The animals were examined weekly for tumor incidence and size (biplanar analysis). Animals were followed up for 240 to 300 days. Tumor incidence was not statistically affected. Time to appearance (latency period) of both tumors and cancers were prolonged by NMF, DMSO, and 4% MSM. Doubling times of all cancers produced were prolonged by DMSO and RA. No group exhibited toxic reactions or significant weight loss. Polar solvents and differentiating agents, specifically NMF, DMSO, and 4% MSM, were effective in the chemoprevention of dimethylbenzanthracene-induced mammary cancers. PMID- 3098208 TI - Weight gain, feed conversion efficiency and plasma free lysine as response criteria in evaluating supplements of lysine plus threonine and lysine plus tryptophan to deficient diets for rats. AB - Two experiments were conducted on growing male SPF-rats to compare weight gain, feed conversion efficiency and plasma free lysine concentration as response criteria in evaluating adequacy of lysine plus threonine and lysine plus tryptophan supplements to the deficient diets. Two basal semisynthetic diets were prepared limiting in lysine and threonine (Expt. 1) and lysine and tryptophan (Expt. 2). The addition of graded supplements to the basal diets of L-lysine X HCl alone (0.2; 0.4; 0.6; 0.8 and 1.0% of diet) induced imbalance of amino acids resulting in low level of daily weight gain and feed conversion efficiency. Plasma free lysine concentration started to grow linearly from the first supplement of L-lysine X HCl. If rats were fed the diets containing identical supplements of L-lysine X HCl in combination with two supplements of L-threonine (0.2 and 0.4% of diet, Expt. 1) or L-tryptophan (0.05 and 0.1% of diet, Expt. 2), plasma free lysine started to increase before supplements of amino acids were adequate to support maximum weight gain and feed conversion efficiency. this difference in response seems to be caused by different feeding regiment during the growth period of the experiments (ad libitum) and training period prior to blood sampling (feeding twice daily). PMID- 3098210 TI - [Incidence of diverticular disease of the large bowel in non-chagasic and chagasic individuals with and without megacolon]. AB - To study the frequency of association between two common colonic disease in our midst, chagasic megacolon and diverticular disease, we reviewed the barium enemas of 243 patients aged more than 35 years. Diverticula were detected in 22 (21.6%) of the 102 non-chagasic individuals, in 10 (35.7%) of 20 chagasics without megacolon, and in 14 (12.4%) of the 113 chagasics with megacolon. There was a statistically significant difference between the two chagasic groups, but not between each one of them and the non-chagasic group. The incidence of diverticula in the sigmoid colon of the non-chagasic group was significantly higher than in the sigmoid colon of the other two groups studied. Among the patients with association of megacolon and diverticular disease, the diverticula were always located in the nondilated portions of the large bowel. It is suggested that totally unfavorable conditions for the genesis and/or maintenance of diverticula exist in the dilated colon of chagasic patients. PMID- 3098209 TI - Studies on the macromolecular components of the bovine aortic and venous tissue. AB - The glycosaminoglycans (GAG), glycoproteins and collagen in bovine aorta and venous tissue have been studied. The concentration of hyaluronic acid and dermatan sulphate was significantly more in the venous tissue while chondroitin sulphates were higher in the aorta. Sequential extraction with phosphate buffered saline (PBS) collagenase, hyaluronidase and urea was also carried out with the two tissues. The GAG extractable by PBS and collagenase digestion were more in the aorta. The total aortic glycoproteins had significantly lower hexose and higher sialic acid. The PBS extractable glycoproteins of the venous tissue had more hexose and fucose. The glycoproteins released by collagenase digestion of the venous tissue had lower sialic acid and higher fucose, while glycoprotein released by hyaluronidase digestion had lower sialic acid and higher hexose and fucose. Urea extractable glycoproteins had lower fucose and sialic acid in the venous tissue. Venous tissue had higher total collagen and acid and salt soluble collagen while insoluble collagen was more in the aorta. The total GAG in the venous tissue had greater anticoagulant activity while the aortic GAG bound significantly more serum lipoproteins. PMID- 3098211 TI - Gastric emptying in children. IV. Studies on kwashiorkor and on marasmic kwashiorkor. AB - Gastric emptying of 20 ml/kg body weight of 5% glucose was assessed by the double sample test meal in 22 malnourished hospitalized children divided into two groups according to the form of malnutrition presented: kwashiorkor (n = 11) or marasmic kwashiorkor (n = 11). Gastric emptying tests were carried out within 72 hours of admission and 30 days later when nutritional status was in net recovery. The control group consisted of seven healthy children who were submitted to a single test. The volumes remaining in the stomach of the children in the kwashiorkor group after the initial test did not differ significantly from those obtained after the second test, when recovery of nutritional status had started. In marasmic kwashiorkor children, intragastric liquid volumes 30 minutes after the test meal were significantly higher in newly-admitted children than in controls, but the differences disappeared after recovery had started. We conclude that kwashiorkor children have no detectable abnormalities of the gastric emptying of a liquid meal, whereas marasmic kwashiorkor malnourished children have delayed gastric emptying but the abnormality is reversible after recovery of nutritional status. PMID- 3098213 TI - Changes in prolactin in peripheral plasma during lactation in the brushtail possum Trichosurus vulpecula. AB - A heterologous double-antibody radioimmunoassay has been validated for prolactin in plasma and pituitary preparations of T. vulpecula. Serial dilutions of crude pituitary homogenates and plasmas from several marsupials and purified prolactin from the tammar, Macropus eugenii, showed parallel dose response curves. In both male and female possums plasma prolactin concentrations increased in response to a single intravenous injection of thyrotrophin releasing hormone. Plasma prolactin concentrations were measured in six lactating females (June-November) and in four non-lactating females (July-October). In the following year prolactin levels were also measured in 11 possums with young less than 50 days old and in 24 possums with young aged between 100 and 145 days. In early lactation prolactin concentrations were low (less than 8 ng/ml) but increased to high levels (greater than 30 ng/ml) by 120 days and remained high until about 160 days of lactation. Thereafter concentrations declined although the young continued to take milk from the mother for a further 30-50 days. The changes in plasma prolactin concentrations throughout lactation are very similar to those described for the tammar, and this unusual pattern appears to be common to marsupials. Non lactating possums showed no consistent changes in plasma prolactin concentrations between July and October. PMID- 3098214 TI - Epidermal cell populations and antigen expression in cultures of human neonatal epidermis. AB - The persistence of Langerhans cells, melanocytes and ABH red cell antigens in human epidermal cell cultures derived from neonatal foreskin explants has been investigated. Langerhans cells were recognised via the detection of ATPase activity and by immunohistochemical staining for T6 and HLA-DR antigens. Melanocytes were detected by the dihydroxyphenylalanine (DOPA) technique; whilst the presence of red cell antigens was confirmed by immunohistochemical tests using monoclonal anti-A, anti-B, and anti-H antibodies. Langerhans cells were not detected in the cultured epidermis, and few melanocytes were found more than 0.2 mm from the periphery of the explants. However, both Langerhans cells and melanocytes were found to persist for up to 4 weeks in the explants themselves. Red cell antigens, consistent with the blood group of the donor infant, were consistently detected on the surface of the differentiating keratinocytes throughout their in vitro lifespan. The significance of these findings is discussed. PMID- 3098212 TI - [Levels of contaminant zinc in solutions routinely used in rehydration and/or parenteral feeding]. AB - With the objective to evaluate the zinc needs of children submitted to rehydration and/or parenteral nutrition, the content of contaminating zinc was determined in intravenous solutions utilized at University Hospital of Ribeirao Preto, SP, Brazil. Zinc was measured in 40 bottles containing deionized water and submitted to the routine treatment for industrialization of serum for parenteral use, according to the standards of the University Hospital of Ribeirao Preto, Industrial Pharmacy. The effect of the sealing material employed (polished red stopper and unpolished black stopper) was observed, as well as time of contact between the solutions and rubber stoppers and latex slides, and the method of bottle conditioning (vertical or horizontal position) which permits contact of the solutions with the rubber stoppers. The gluco-saline solutions prepared in our Hospital and stored in glass bottles with unpolished black rubber stoppers and latex slide showed substantial zinc levels (1,220 to 4,860 micrograms/ml, n = 30). The same solutions kept in glass vials or plastic bottles were zinc free. The highest zinc levels were observed in the amino acid solutions placed in sealed bottles with unpolished black rubber stoppers (11,690 to 24,310 micrograms/ml, n = 20). It is important to be aware of these contaminating zinc levels to provide proper treatment involving this micronutrient. PMID- 3098215 TI - Resistance of 129/J mice to Schistosoma mansoni infection. AB - Mice of the strain 129/J bred at this Institute (WEHI 129/J) were exposed once or repeatedly to cercariae of Schistosoma mansoni and worm burdens determined. In keeping with reports of S. japonicum infection in these mice, a high level of resistance was recorded. Radio-labelled extracted antigens of S. mansoni adult worms were reacted with sera from exposed 129/J mice and infected BALB/c mice. Immunoprecipitated antigens preferentially recognized by antibodies in 129/J mice include proteins of Mr 99,000 and 21,000. Whether responses to these antigens are a cause or a consequence of resistance remains to be established. PMID- 3098216 TI - Inhibition of breathing movements in fetal life: relevance to the sudden infant death syndrome. AB - Fetal breathing movements are discontinuous and are inhibited by neural mechanisms associated with the development of non-rapid eye movement sleep. Sudden reduction of arterial PO2 also reduces the incidence of breathing movements in the fetus. Recent work which is directed towards identifying the control pathways and neurotransmitters involved in these effects is discussed. The possibility that breathing may also be inhibited in certain situations after birth is addressed, particularly in relation to the ability of hypoxaemia to produce behavioural arousal in the normal newborn infant, but not in fetal life. PMID- 3098218 TI - [Parenteral nutrition with special reference to the fat supply. Symposium. Stockholm, 13-14 October 1984]. PMID- 3098217 TI - [Energy metabolism in surgical patients]. PMID- 3098219 TI - [Evaluation of the efficiency of parenteral nutrition]. PMID- 3098220 TI - [Peculiarities of carbohydrates and lipids in parenteral nutrition of severely ill patients]. PMID- 3098221 TI - [Compatibility with fat emulsions]. PMID- 3098222 TI - [Future developments in parenteral nutrition]. PMID- 3098223 TI - [Organization of a parenteral nutrition program for post-stress metabolism with reference to existing metabolic changes]. PMID- 3098224 TI - [Is there an optimal calorie-nitrogen relationship?]. PMID- 3098225 TI - [Metabolic disorders in patients with severe craniocerebral traumas]. PMID- 3098226 TI - [Metabolic peculiarities and clinical sequelae in nutrition of cancer patients]. PMID- 3098227 TI - [When is parenteral carnitine administration indicated?]. PMID- 3098228 TI - Response to exercise of patients with severe chronic heart failure. PMID- 3098229 TI - A carnitine/acylcarnitine translocase assay applicable to biopsied muscle specimens without requiring mitochondrial isolation. AB - A simple method for assaying the mitochondrial carnitine/acylcarnitine translocase of muscles that needs only few milligrams of fresh tissue is described. The procedure involves monitoring of the sulphobetaine (an inhibitor of the translocase)-sensitive acetylation of sub-saturating concentrations of carnitine in the medium, linked to the oxidation of [2-14C]pyruvate in the presence of malonate. Conditions affecting the reliability of the outlined procedure and the ancillary information to be collected, namely the activities of pyruvate oxidase system and carnitine acetyltransferase, for detecting possible deficiency of the translocase are described, together with data on the translocase activity in human skeletal muscle, in rat red and white skeletal muscles and in rat heart. The concepts outlined should allow development of assays of other mitochondrial transporters that also would require neither isolation of mitochondria nor availability of a large quantity of tissue, both of which are otherwise needed at present. PMID- 3098230 TI - Steady-state kinetic analysis of soluble methane mono-oxygenase from Methylococcus capsulatus (Bath). AB - A steady-state kinetic analysis of purified soluble methane mono-oxygenase of Methylococcus capsulatus (Bath) was performed. The enzyme was found to follow a concerted-substitution mechanism. Methane binds to the enzyme followed by NADH, which reacts to yield reduced enzyme and NAD+. The reduced enzyme-methane complex binds O2 to give a second ternary complex, which breaks down to release water and methanol. In this way the enzyme can control the supply of electrons to the active site to coincide with the arrival of methane. Product-inhibition studies (with propylene as substrate) supported the reaction mechanism proposed. Ki values for NAD+ and propylene oxide are reported. The Km for NADH varied from 25 microM to 300 microM, depending on the nature of the hydrocarbon substrate, and thus supports the proposed reaction sequence. With methane as substrate the Km values for methane, NADH and O2 were shown to be 3 microM, 55.8 microM and 16.8 microM respectively. With propylene as substrate the Km values for propylene, NADH and O2 were 0.94 microM, 25.2 microM and 12.7-15.9 microM respectively. Methane mono-oxygenase was shown to be well adapted to the oxidation of methane compared with other straight-chain alkanes. PMID- 3098231 TI - Inositol phospholipid arachidonic acid metabolism in GH3 pituitary cells. AB - Inositol phospholipids in cultured GH3 cells, a prolactin secreting, thyrotropin releasing hormone (TRH) sensitive rat pituitary cell line, exhibit a preferential selectivity for incorporating arachidonic acid. Fatty acid composition data show that all inositol phospholipids are enriched in stearic and arachidonic acids to a much greater degree than other cellular phospholipids. Incubation of GH3 cells with radioactive stearate, oleate, arachidonate, eicosapentaenoate or docosahexaenoate also showed that much more stearate and arachidonate were incorporated into inositol phospholipids. In short term incubations with tracer amounts of radioactive arachidonate, incorporation was initially into phosphatidylinositol (PtdIns), with phosphatidylinositol 4-phosphate (PtdIns4P), and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] being labelled at later times. During longer incubations, all of the inositol phospholipids reach equilibrium at about 10 h, and the resulting specific activities of the three fractions were similar. These findings suggest that arachidonate is incorporated initially into PtdIns and that PtdIns is then phosphorylated. There was no release of either arachidonate or eicosanoid products when GH3 cells were incubated with TRH. However, TRH stimulation of 32P-labelled GH3 cells resulted in rapid breakdown of PtdIns(4,5)P2 and PtdIns4P, with concomitant increases in [32P]phosphatidic acid and [32P]PtdIns. When the [32P]PtdIns was further analysed by argentation chromatography to separate PtdIns molecular species, it was found that tetraenoic (stearate/arachidonate) species accounted for 80% of the stimulated labelling. The selectivity for arachidonate incorporation into inositol phospholipids coupled with turnover of the arachidonate-containing molecular species suggests that inositol phospholipids containing arachidonic acid or the diacylglycerol resulting therefrom may play a vital cellular role in GH3 cells. This role may involve the operation of the PtdIns cycle itself rather than a stimulated release of arachidonate for eicosanoid formation. PMID- 3098232 TI - Arachidonic acid turnover in response to lipopolysaccharide and opsonized zymosan in human monocyte-derived macrophages. AB - Macrophages are an important source of the lipid mediators, arachidonic acid metabolites and platelet-activating factor (PAF), produced during inflammation. Studies were undertaken to identify the phospholipid substrates that can serve as a source of arachidonic acid in human monocyte-derived macrophages exposed to the inflammatory stimuli bacterial lipopolysaccharide (LPS) and opsonized zymosan (OpZ). Since PAF is derived from 1-alkyl-2-acyl-glycerophosphocholine, it was of interest to determine if this phospholipid precursor could also serve as a source of arachidonic acid. The day-5 macrophages incorporated 38% of the available [3H]arachidonic acid into lipid by 4 h, 54% of which was in phospholipid [phosphatidylcholine (PC) greater than phosphatidylethanolamine (PE) greater than phosphatidylinositol (PI)]. The proportion of label incorporated into ether linked PC and PE increased with time. After prelabelling with [3H]arachidonic acid, the effect of stimuli on the redistribution of label within phospholipids was followed. Without stimulus there was a loss of label from PC, PI and phosphatidic acid by 3 h, but an increase of label in PE. The [3H]arachidonic acid that was lost from PC in the absence of stimulus was derived solely from the 1-acyl-linked species of PC, whereas an increase in label occurred in the 1-alkyl linked species of PC. By contrast, LPS stimulation resulted in a preferential, dose-dependent loss of label from PC and PI, which was maximal between 1 and 3 h after adding the LPS. In addition, LPS induced a 35% decrease in the molar quantity of PI in the macrophages but had no effect on the quantity of PC, PE or phosphatidylserine. Stimulation with OpZ also resulted in a loss of label, mainly from PC and PI. Of the total label lost from PC in response to LPS or OpZ, approx. 50% was derived from the 1-alkyl-linked species. The results suggest that phospholipase C- and phospholipase A2-mediated mechanisms for arachidonic acid release are activated in human macrophages exposed to the inflammatory stimuli LPS and OpZ. In addition, 1-alkyl-linked PC can serve as a source of arachidonic acid and as a precursor for PAF production in the stimulated macrophages. PMID- 3098234 TI - Complete amino acid sequence of cyanobacterial gas-vesicle protein indicates a 70 residue molecule that corresponds in size to the crystallographic unit cell. AB - Gas vesicles of cyanobacteria are formed by a protein called 'gas-vesicle protein' (GVP). The complete amino acid sequence has been determined of GVP from Anabaena flos-aquae. It is 70 residues long and has an Mr of 7388. This corresponds to the size of the repeating unit cell demonstrated by X-ray crystallography of intact gas vesicles. Details of the sequence are related to the secondary beta-sheet structure of the protein and its contrasting hydrophilic and hydrophobic surfaces. Extensive amino acid sequences have also been determined for GVPs from two other cyanobacteria, species of Calothrix and Microcystis; they are highly homologous with that of Anabaena GVP. Electrophoretic analysis indicates that GVPs of different cyanobacteria form a variety of stable oligomers. PMID- 3098233 TI - Monoclonal antibodies to the guanine-nucleotide binding proteins of adenylate cyclase. AB - Monoclonal antibodies (Mabs) to the stimulatory (Ns) and inhibitory (Ni) guanine nucleotide regulatory proteins associated with adenylate cyclase have been developed. Two Mabs (2A3 and 5G12), which are of the IgG2b subclass, recognize the beta-subunits (beta) of Ns, Ni and transducin. Iodinated beta can be immunoprecipitated by either Mab coupled to Affi-Gel 10 and this can be decreased by prior incubation of the Mabs with excess unlabelled beta. The Mabs stabilize the activated state of Ns while decreasing the rate of deactivation of activated Ns in the presence of beta. PMID- 3098235 TI - Reconstitution of surfactant activity by using the 6 kDa apoprotein associated with pulmonary surfactant. AB - Lipid extracts of bovine pulmonary surfactant containing the 6 kDa apoprotein, but lacking the 35 kDa apoprotein, can mimic the essential characteristics of pulmonary surfactant on a pulsating-bubble surfactometer. Reconstituted surfactant can be produced by combining silicic acid fractions containing 6 kDa apoprotein and phosphatidylglycerol with phosphatidylcholine. Treatment of the protein-containing fraction with proteolytic enzymes abolishes its efficacy. These results indicate that the presence of the 6 kDa apoprotein can account for some of the essential physical and biological characteristics of pulmonary surfactant. Immunodiffusion studies indicate that, contrary to earlier suggestions, the 6 kDa apoprotein is not structurally related to the major surfactant apoprotein that has a molecular mass of 35 kDa. PMID- 3098236 TI - Cystine transport in purified rat liver lysosomes. AB - Amino acid efflux from highly purified rat liver lysosomes exposed to the methyl ester derivatives of leucine, methionine, tyrosine and cystine was examined. The lysosomal efflux of leucine, methionine and tyrosine was unaffected by the presence of MgATP, whereas cystine efflux was stimulated by MgATP. Exposure of lysosomes to 2 mM-MgATP resulted in lysosomal acidification and a 0.5 pH unit increase in the lysosomal pH gradient through the action of a proton-pumping ATPase. Cystine efflux was also stimulated when the lysosomal proton gradient was increased through changes in buffer pH. Decreasing the lysosomal proton gradient with ionophores resulted in diminished cystine efflux. Bivalent cations had no effect on the lysosomal efflux of leucine, methionine and tyrosine. However, cystine efflux was stimulated by the presence of bivalent cations even when the lysosomal proton gradient was minimized. Cation-stimulated cystine efflux was inhibited by the presence of the calcium ionophore A23187, which altered the lysosomal membrane potential. Cystine efflux from lysosomes appears to be uniquely dependent on pH gradients and cation concentrations. PMID- 3098237 TI - The W and L allelic forms of phenylalanine hydroxylase in the rat differ by a threonine to isoleucine substitution. AB - High performance liquid chromatography maps of tryptic and chymotryptic peptides from the W and L forms of rat phenylalanine hydroxylase differed by one peptide. Sequencing of the variant tryptic peptides showed a substitution of threonine in the W form by isoleucine in the L form and this same difference was confirmed in the chymotryptic peptides. This allelic substitution would result from a nucleotide change of ACA to ATA at amino acid position 371 of the full phenylalanine hydroxylase sequence. Altered sodium dodecyl sulphate binding is postulated to explain the change in mobility of the proteins observed on sodium dodecyl sulphate/polyacrylamide gels. PMID- 3098238 TI - Vitamin K antagonism of coumarin anticoagulation. A dehydrogenase pathway in rat liver is responsible for the antagonistic effect. AB - In the liver, it appears that there are two different pathways for vitamin K reduction. One pathway is irreversibly inhibited by coumarin anticoagulant drugs. The other pathway has been shown in the present study to be composed of enzymes that are not effected by physiological 'in vivo' concentrations of these drugs. This pathway appears to be responsible for the antidotal effect of vitamin K in overcoming coumarin poisoning. In rat liver the pathway has been shown to be composed of DT-diaphorase (EC.1.6.99.2) and a microsomal dehydrogenase(s). The activity of the microsomal dehydrogenase(s) was 3.6-fold higher with NADH than with NADPH present in the test system. It appears that this enzyme is the physiologically important enzyme in the pathway. In contrast with DT-diaphorase, this enzyme(s) is shown to be tightly associated with the mirosomal membrane. The enzyme(s) is not identical with either of the quinone-reducing enzymes cytochrome P-450 reductase or cytochrome-b5 reductase. Our data thus postulate the existence of an as-yet-unidentified microsomal dehydrogenase that appears to have an important function in the pathway. PMID- 3098239 TI - Oligosaccharides obtained from a blood-group-Sd(a+) Tamm-Horsfall glycoprotein. An n.m.r. study. AB - Treatment of Tamm-Horsfall urinary glycoprotein with Bacteroides fragilis endo beta-galactosidase over a range of enzyme concentrations, pH and temperature resulted in the release of a small but constant proportion of the terminal sugars, which indicates the presence in the glycoprotein of relatively few enzyme susceptible -GlcNAc beta 1-3Gal beta 1-4GlcNAc- units. Three oligosaccharides were isolated from the enzyme digest and characterized as Gal beta 1-4GlcNAc beta 1-3Gal, NeuAc alpha 2-3Gal beta 1-4 GlcNAc beta 1-3Gal and GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta 1-4GlcNAc beta 1-3Gal by methylation analysis and exo glycosidase digestion. The alditols of these oligosaccharides and related structures were examined by 500 MHz 1H-n.m.r. spectroscopy aided by spin-spin decoupling and two-dimensional correlated spectroscopy. An almost complete assignment of proton shifts was possible, and significant differences between the signals of some of the protons in the blood-group-Sda-active oligosaccharide III and literature values for the corresponding signals in the structurally related Cad-blood-group determinant are noted. PMID- 3098242 TI - T-cell differentiation antigens: proteins, genes and function. PMID- 3098240 TI - Complete structure of the hydrophilic domain in the porcine NADPH-cytochrome P 450 reductase. AB - The 622-residue amino acid sequence of the hydrophilic domain in the porcine NADPH-cytochrome P-450 reductase (EC 1.6.2.4) is reported. The structural data required to complete the sequences published previously [Vogel, Kaiser, Witt & Lumper (1985) Biol. Chem. Hoppe-Seyler 366, 577-587] and to establish the primary structure of the porcine hydrophilic domain have been obtained by sequencing proteolytic subfragments derived from CNBr fragments and by characterizing the overlapping S-[14C]methylmethionine-containing peptides isolated from tryptic digests of the [14C]methyl-labelled hydrophilic domain. The hydrophilic domain displays 91.8% positional identity with that of the corresponding domain in the rat NADPH-cytochrome P-450 reductase. The region Val528-Ser678 in the NADPH cytochrome P-450 reductase shows a significant homology to the sequence Ile165 Tyr314 in the spinach ferredoxin-NADP+ oxidoreductase. A model for the secondary structure of the hydrophilic domain has been derived by computer-assisted analysis of the amino acid sequence. Cys472 and Cys566 are protected against chemical modification in the NADP+ complex of the NADPH-cytochrome P-450 reductase. PMID- 3098241 TI - Comparative studies on the energetics of platelet responses induced by different agonists. AB - The correlation between energy consumption and platelet responses induced by collagen, A23187 and ADP was investigated and compared with the energetics of thrombin-stimulated platelets established in earlier work. Aggregation, measured as single-platelet disappearance, and secretion correlated quantitatively with the increment but not with the total consumption of energy, suggesting that the former reflects the energy cost of these responses. The cost of complete aggregation was 2-3 mumol of ATP equivalents/10(11) platelets with collagen, ADP and thrombin as the stimulus. The cost of complete dense-granule secretion was 0.5-0.8 mumol of ATP equivalents/10(11) platelets with all agonists tested. The cost of combined secretion of alpha-granule and acid hydrolase granule contents was 5-7 mumol of ATP equivalents/10(11) platelets with thrombin and collagen. However, in the presence of A23187 much more energy was consumed during aggregation and secretion. Also ADP triggered more energy consumption during secretion than was seen with the other inducers. The effect of inhibitors of aggregation and secretion was investigated in thrombin-stimulated platelets. Raising the cellular cyclic AMP content sharply decreased the increment in energy consumption as well as aggregation and secretion. The cytoskeleton-disrupting agents cytochalasin B and colchicine left the increment in energy consumption intact, but decreased the basal consumption seen in unstimulated platelets. This was accompanied by normal (cytochalasin B) or diminished (colchicine) aggregation and secretion. Apart from the latter exception, all inhibitors decreased secretion and incremental energy consumption in parallel, thereby preserving the energy-versus-secretion relationship established in earlier work. In contrast, aggregation and energy consumption varied independently, suggesting that the coupling with energy consumption is much weaker for this response. PMID- 3098243 TI - Gamma interferon and calcitriol formation by human macrophages. PMID- 3098244 TI - Archaebacteria: the road to the universal ancestor. PMID- 3098245 TI - Kinetic investigations into the interactions of aprophen with cholinesterases and a carboxylesterase. AB - Acetylcholinesterases, butyrylcholinesterases, and carboxylesterases appear to form kinetically a homologous enzyme series with respect to many substrates and inhibitors. The present paper evaluates the interaction of aprophen with acetylcholinesterases, butyrylcholinesterases, and carboxylesterases with respect to protecting the enzyme from organophosphate and carbamate inhibition, accelerating pralidoxime iodide (2-PAM) regeneration of the diisopropylphospho enzyme, and comparing the inhibition and regeneration kinetics of a soluble mammalian acetylcholinesterase with that of bovine erythrocyte acetylcholinesterase. The irreversible inhibition kinetics of diisopropyl fluorophosphate (DFP) and eserine inhibition of fetal bovine serum acetylcholinesterase were typical of other acetylcholinesterases as indicated by the bimolecular inhibition rate constants, ki, of 7.7 +/- 1.3 X 10(4) M-1 min-1 and 2.9 +/- 1.7 X 10(6) M-1 min-1, respectively. Similarly, the bimolecular regeneration rate constant, kr, for 2-PAM regeneration of the diisopropylphospho acetylcholinesterase was 14.7 M-1 min-1. The bimolecular rate constants, ki and kr, were not statistically perturbed when the reaction was monitored in the presence of aprophen with the fetal bovine serum acetylcholinesterase. Human serum butyrylcholinesterase was partially protected from DFP inhibition by aprophen with no detectable change in the bimolecular inhibition rate constant, ki. The regeneration of the diisopropylphospho-butyrylcholinesterase by 2-PAM was accelerated in the presence of aprophen by a factor of 2.7 over that of 2-PAM alone (8.4 +/- 2.2 M-1 min-1 to 23.1 +/- 2.6 M-1 min-1 respectively). Neither the inhibition (DFP) nor the regeneration (2-PAM) kinetics observed for the carboxylesterase was perturbed by the presence of aprophen. PMID- 3098246 TI - Adenosine analog metabolism in Giardia lamblia. Implications for chemotherapy. AB - Certain adenosine analogs can inhibit the growth of Giardia lamblia. This biological action correlates with the ability of the organism to phosphorylate the nucleoside directly to the nucleotide. Four of these, 8-azaadenosine, 1 deazaadenosine, 7-deazaadenosine, and 9-deazaadenosine, were very effective. The respective bases of the first three were ineffective. The base of 9 deazaadenosine was not tested as this C-nucleoside is non-cleavable. Metabolic studies using radioactive 7- and 9-deazaadenosine showed that these compounds were phosphorylated by the organism. Enzymatic assay confirmed the presence of nucleoside phosphotransferase activity; no nucleoside kinase activity was found. Preliminary characterization of this phosphotransferase suggests that it has different substrate and phosphate donor specificities than the mammalian enzyme and, therefore, may be a potential site for chemotherapeutic attack. PMID- 3098247 TI - Changes in biliary secretion and lactate metabolism induced by diethyl maleate in rabbits. AB - Diethyl maleate is a compound which binds with glutathione by means of a glutathione S-transferase and is excreted into bile leading to a rapid depletion of hepatic glutathione. In the rabbit, the activity of the enzyme is fairly low and we were thus prompted to study the possible effects of diethyl maleate on biliary secretion and metabolic status in this species. The administration of diethyl maleate induced a transient choleresis followed by cholestasis. The choleresis coursed with increases in the biliary output of sodium and unaccounted anions, whereas those of chloride, bicarbonate and bile acids were unaffected. Our data seem to confirm that choleresis is due to the osmotic activity of diethyl maleate compounds excreted into bile, as has been reported in rats and dogs. The cholestasis observed coursed with falls in the outputs of sodium, chloride and bicarbonate though that of bile acids remained constant. Following diethyl maleate administration, a metabolic acidosis appeared with progressive increases of blood lactate concentration. In bile the concentration of this anion closely followed that of plasma. The cholestasis is attributed to a lowered biliary secretion of bicarbonate probably secondary to the metabolic alteration. The hepatic values of cytoplasmatic and mitochondrial NADH/NAD ratios and of adenine nucleotide concentrations suggest that the increase in blood lactate results rather from a fall in its hepatic utilization that from an increase in its production. PMID- 3098248 TI - Inhibition of prostacyclin synthesis in cultured bovine aortic endothelial cells by vitamin K1. AB - Prostacyclin (PGI2), a potent vasodilator and inhibitor of platelet aggregation, is the predominant metabolite of arachidonic acid (AA) in endothelial cells derived from large blood vessels. Vitamin K1 (1-100 microM) inhibited the release of PGI2 and prostaglandin E2 (PGE2) by bovine aortic endothelial cells in culture, as measured by radioimmunoassay of 6-keto-prostaglandin F1 alpha (6-keto PGE1 alpha) and PGE2. The conversion of exogenous AA to PGI2 was not affected by vitamin K1 as measured by radioimmunoassay and high performance liquid chromatography of radiolabeled AA metabolites. Similarly, vitamin K1 did not affect the conversion of prostaglandin H2 (PGH2) by in vitro enzyme systems. However, vitamin K1 inhibited the calcium ionophore A23187-induced release of [3H]AA from membrane phospholipids of bovine aortic endothelial cells. Inhibition of [3H]AA release from other cells of vascular origin was also observed after exposure to vitamin K1, but this effect was not observed in cells of non-vascular origin, including platelets. Therefore, vitamin K1 modulates the release of AA in vascular cells and thus inhibits the capacity of blood vessels to synthesize PGI2. PMID- 3098250 TI - Participation of microsomal electron transport systems in nicotine metabolism by livers of guinea pigs. PMID- 3098249 TI - Effect of acetylsalicylic acid on gastric mucin viscosity, permeability to hydrogen ion, and susceptibility to pepsin. AB - The effect of acetylsalicylic acid (aspirin) on peptic degradation of gastric mucin, its viscosity and the ability to retard the diffusion of hydrogen ion was investigated. The results of peptic degradation indicated that, in the absence of the drug, the rate of proteolysis was proportional to mucin concentration up to 400 micrograms and remained constant with time for up to 1 hr. Introduction of aspirin led to an enhancement in the rate of proteolysis. The apparent Km value of pepsin toward mucus glycoprotein was 8.7 X 10(-7) M in the absence of the drug and 6.9 X 10(-7) M in its presence. Viscosity measurements showed a drop in mucin viscosity following preincubation with aspirin. This decrease was concentration dependent and at a 4.0 X 10(-5) M concentration of the drug reached a value of 75%. Permeability studies revealed that preincubation with 2.0 X 10(-5) M aspirin increased the permeability of mucin to hydrogen ion by 10%, while an 18% increase was obtained with 4.0 X 10(-5) M aspirin. The results suggest that aspirin weakens the integrity of the gastric mucus layer by promoting its peptic degradation, decreasing viscosity, and reducing the ability to resist hydrogen ion penetration. PMID- 3098251 TI - Stimulatory effect of calmodulin antagonists on phospholipid base-exchange reactions in rabbit platelet membranes. AB - The properties of Ca2+-dependent incorporation of [3H]serine, [3H]ethanolamine and [3H]choline into the corresponding phospholipids mediated by base-exchange enzymes in rabbit platelet membranes were studied in the presence or absence of the calmodulin antagonists chlorpromazine, trifluoperazine and N-(6-aminohexyl)-5 chloro-1-naphthalenesulfonamide (W-7), all of which markedly activate three base exchange reactions. The base-exchange activities were dependent on Ca2+ both in the presence and absence of the drugs. Other metal ions tested did not stimulate the base-exchange reactions, even in the presence of the drugs. Apparent Km values for serine, ethanolamine and choline were not affected significantly by the concentration of Ca2+, with or without the drugs. [3H]Serine incorporation into phospholipid was competitively inhibited by ethanolamine and choline, [3H]choline incorporation was competitively inhibited by serine and ethanolamine, whereas [3H]ethanolamine incorporation was competitively inhibited by serine and noncompetitively by choline. These competitive and noncompetitive relations between each base were also not affected by the drugs. The amount of 45Ca2+ binding to platelet membranes was decreased by the drugs dose dependently. A weaker calmodulin antagonist, N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), only slightly stimulated the base-exchange reactions, but did clearly inhibit 45Ca2+ binding to the membranes, in the same manner as that of the other calmodulin antagonists used. The concentration of chlorpromazine, trifluoperazine, W-7 and W-5, required to produce half-maximal inhibition of Ca2+ binding, was approximately 30 microM. These results suggest that the calmodulin antagonists used activate the base-exchange reactions only in the presence of Ca2+ without changing the affinity of each free base to base-exchange enzymes. The activation of the base-exchange reactions was not due to the increase in free Ca2+ caused by the drug-induced inhibition of Ca2+ binding to platelet membranes. PMID- 3098252 TI - Synthetic seleno-organic compound with glutathione peroxidase-like activity in the chick. AB - The glutathione peroxidase activity catalyzed by the seleno-organic anti inflammatory drug Ebselen (registered under the trademark of the Natterman Corp. Cologne, FRG) [PZ51, 2-phenyl-1,2-benzisoselenazol-3(2H)on], as measured by NADPH oxidation, was inhibited in vitro by the selenium-dependent glutathione peroxidase (SeGSHpx) inhibitors aurothioglucose and D-(-)penicillamine HCl. Vitamin E- and selenium-deficient chicks were given 0, 80 or 320 ppm PZ51 in diets devoid of vitamin E and supplemented with low levels of sodium selenite (0.04 ppm selenium added to the basal diet containing ca. 0.015 ppm selenium) when a small number of chicks (ca. 13%) had exudative diathesis (ED). By 24 hr, the high PZ51 dose (320 ppm) delayed the onset of ED compared to untreated controls. Similarly, vitamin E-deficient chicks fed diets containing 0, 80, 160, 320, 640 or 1280 ppm PZ51 and supplemented with 0.04 ppm selenium showed ED in inverse proportion to log PZ51 dose. Plasma and liver post-mitochondrial supernatant samples from these chicks also exhibited log-linear relationships between dietary PZ51 level and selenium content or SeGSHpx-like activity. The amount of SeGSHpx-like activity for chicks given PZ51 above that determined for untreated chicks was extractable into ethanol, indicating that those PZ51 associated increases were not due to protein-bound selenium or SeGSHpx. This suggests that selenium from PZ51 was not available to support synthesis of SeGSHpx. Dietary PZ51 (1280 ppm) or selenium (0.1 ppm) alone or in combination decreased the acute lethalities of nitrofurantoin or paraquat in vitamin E adequate chicks. The results indicate that SeGSHpx-like activity in selenium deficient chicks is increased by oral administration of PZ51, which appears to mimic the true enzyme by affording protection against clinical signs of selenium deficiency (i.e. ED) and pro-oxidant drug lethality. PMID- 3098253 TI - Synergistic interactions between piracetam and dihydroergocristine in some animal models of cerebral hypoxia and ischaemia. AB - In pharmacological screening tests for activity against the cerebral insults of hypoxia and ischaemia induced by MgCl2 or decapitation in mice, the combination of piracetam and dihydroergocristine has been shown to produce synergistic effects in prolonging the survival time. This was not the case in the model of histiocytic anoxia induced by KCN. Using an optimal combination of piracetam and dihydroergocristine (533:1, Diemil) significant increases in cerebral resistance to hypercapnic anoxia and reductions in the duration of the ensuing electrical silence on the electrocorticogram have been demonstrated in the rat. The same combination was also effective in antagonizing the memory ablating effects of anoxia in rats subjected to electric footshocks during a standard passive avoidance response. The absence of clear effects on gross cerebral blood flow and metabolism, together with considerations of the known pharmacological properties of the two components of the combination and the effects of standard drugs in the models used, lead to the conclusion that the explanation of the observed synergism probably lies in complimentary actions at the level of the cerebral neurones and is independent of simple vasodilation. PMID- 3098254 TI - Potentiation of clobazam's anticonvulsant activity by etifoxine, a non benzodiazepine tranquilizer, in mice. Comparison studies with sodium valproate. AB - The interaction of two tranquilizers, the 1,5-benzodiazepine clobazam (CBZ, Frisium) and the non-benzodiazepine etifoxin (Hoe-36,801) hydrochloride (EFX, 6 chloro-2-ethylamino-4-methyl-4-phenyl-4H-3,1-benzoxazine HCl) was investigated for anticonvulsant activity in mice. Corresponding experiments were performed with the antiepileptic drug sodium valproate (VPA). Tonic-clonic (maximal) seizures were induced by maximal electroshock (MES; 12 mA, 200 ms) and clonic (threshold) seizures by pentetrazol (PTZ; 85 mg/kg s.c.). The addition of an anticonvulsant threshold dose of EFX (50 mg/kg p.o.) led to an increase of CBZ's potency against both MES- and PTZ-seizures by 410 or 450%, respectively. Under the same conditions, EFX enhanced the potency of VPA only by 20 or 80% and a threshold dose of VPA (100 mg/kg p.o.) enhanced the potency of CBZ by 110 or 0%, respectively. It is concluded that this potentiation of CBZ's anticonvulsant activity by EFX may be beneficially used in epileptic patients either to increase CBZ's antiepileptic effects or to reduce CBZ's therapeutic doses in order to prevent or delay the development of resistance. PMID- 3098255 TI - Prevention of the acetylsalicylic acid-induced changes of the gastric potential difference by the new synthetic prostaglandin E1 analogue rioprostil. AB - The protective effect of 50 and 100 micrograms of the synthetic prostaglandin E1 analogue rioprostil (2-decarboxy-2-hydroxymethyl-15-deoxy-16RS-hydroxy-16-methyl PGE1) against the 0.5 and 1 g acetylsalicylic acid (ASA)-induced changes of gastric potential difference (PD) was compared to that of placebo in a double blind cross-over study in 8 volunteers. Rioprostil 50 and 100 micrograms reduced significantly (p = 0.45) the intensity (area under baseline) of the 0.5 g ASA induced PD changes. Both doses reduced highly significantly (p = 0.003) the time taken for PD to return to baseline value (15.1 min with 50 micrograms and 17.2 min with 100 micrograms rioprostil vs 43.5 min with placebo). Both doses of rioprostil also reduced significantly (p = 0.04) the PD maximal drop induced by 1 g ASA and reduced highly significantly (p = 0.006) the time taken for PD to return to baseline value (18.9 min with 50 micrograms and 16.8 min with 100 micrograms rioprostil vs 64.6 min with placebo). This study shows that rioprostil protects the stomach against the ASA-induced alterations of the gastric mucosa even when it is given at the same time as ASA and in doses which have only a small antisecretory effect. PMID- 3098256 TI - A calculator program for determining indices of neonatal respiratory distress syndrome severity. AB - The potential for treating and preventing neonatal respiratory distress syndrome (RDS) with exogenous surfactant has created renewed interest in quantitative measures and derived scores that can be used to assess disease severity. Many different indices of RDS severity have been suggested. They are useful as outcome measures in clinical trials and may assist in the early identification of infants at risk for severe complications. In this article, a program for the Hewlett Packard 41CV programmable calculator is presented that calculates indices of RDS severity based on ventilator settings and arterial blood gas values. PMID- 3098257 TI - Medium-chain triglycerides in neonatal nutrition. Absence of inhibition of lipogenesis and of laxative effect. AB - Eighteen neonates ranging in birthweight from 820 to 1570 gm and in gestational age from 29 to 35 weeks were assigned alternately and blindly to feedings with formulas containing 14 or 50% of their fat as medium-chain triglycerides (MCT). Mean daily intakes of formula and mean daily weight gains were similar in neonates in the two groups. Consistency of stools and mean weekly increments in skinfold thickness were not affected by the MCT content of the formula. This suggests that under ordinary clinical conditions, medium-chain triglycerides exert no laxative effect nor affect adversely the deposition of subcutaneous fat in very low-birthweight neonates. PMID- 3098258 TI - Development of a radioimmunoassay for the immunodiagnosis of schistosomiasis mansoni. PMID- 3098259 TI - Effect of paraventricular nucleus lesions on body weight, food intake and insulin levels. AB - Lesions of the paraventricular nucleus of the hypothalamus (PVN) produce obesity and hyperphagia. However, the underlying mechanism is unknown. The connections of the PVN with brainstem centers for autonomic control suggest that a change in autonomic function could mediate the PVN obesity syndrome. We examined this hypothesis in a series of 3 experiments, searching specifically for changes in insulin secretion. Rats with PVN lesions were hyperphagic and hyperinsulinemic, when obese. However, hyperinsulinemia could not be detected prior to the onset of obesity or following weight reduction. Subdiaphragmatic vagotomy reversed the PVN obesity and lowered insulin levels below those of sham-vagotomized rats. Since noradrenergic innervation of the hypothalamus is implicated in feeding, hypothalamic norepinephrine (NE) was depleted by injection of 6-hydroxydopamine into the central tegmental tract, posterior to the hypothalamus. The effects of NE depletion was compared with those of PVN lesions. Loss of hypothalamic NE resulted in hyperphagia with no increase in body weight and no change in insulin. Histological analyses indicated that the posterior PVN was the most effective lesion focus for producing disturbances in body weight and food intake. Although the results of these experiments implicate the autonomic nervous system in PVN obesity, basal hyperinsulinemia does not appear to be a primary feature of the syndrome. PMID- 3098260 TI - Structure and function of L-lactate dehydrogenases from thermophilic and mesophilic bacteria, IV. The primary structure of the mesophilic lactate dehydrogenase from Bacillus subtilis. AB - The complete amino-acid sequence of lactate dehydrogenase from the mesophilic Bacillus subtilis (B. X1) was determined. Approximately 70% of the sequence was obtained by sequence analysis of intact protein (N-terminal sequence) and of four CNBr fragments (CNBr3, CNBr4, CNBr5 and CNBr6). Sequences overlapping the CNBr fragments were determined from polypeptide fragments obtained by cleavage using o iodosobenzoic acid (cleavage at Trp) or clostripain (cleavage at Arg). The C terminal amino-acid residue (Asn) was detected by carboxypeptidase Y-degradation. Lactate dehydrogenase from B. subtilis shows a 69% sequence homology to that from the thermophilic strain B. stearothermophilus, and a 34% sequence homology to those from higher organism. The homology of these enzymes is particularly high at the active site regions (the coenzyme and substrate binding sites). The relatively high sequence conservation of the lactate dehydrogenases from B. subtilis and B. stearothermophilus (and from other bacilli) allows a structural comparison of this temperature variants. PMID- 3098262 TI - [Effects of carbaryl on growth and morphogenesis of the chick embryo]. PMID- 3098261 TI - Endotoxin-induced TxB2 release by polymorphonuclears and macrophages. PMID- 3098263 TI - Alterations of Aplysia feeding behavior following acute carbamate intoxication. PMID- 3098264 TI - [Diagnosis of pyruvate dehydrogenase complex deficiency in biopsied muscles and cultured skin fibroblasts]. PMID- 3098265 TI - [The effect of hyperoxemia on cerebral blood flow in normal humans]. AB - The aim of this study was to evaluate the effect of various degrees of hyperoxemia on cerebral blood flow (CBF), including the hyperbaric oxygenation (HBO) environment. Study subjects were 28 healthy volunteers (17 males and 9 females) from 26 to 60 (average: 42 +/- 11) years old. CBF measurements were done by 19 mCi 133Xe intravenous injection method using rCBF analyzer BI-1400 (Valmet). Two-compartmental analysis was used for the calculation of Fast, Slow Flow and initial slope index (ISI). The three CBF study series included: Rest (before HBO 1 ATA.air)-1 ATA.O2-2 ATA.O2 series in 8 cases; Rest-1 ATA.O2 50% N2 50%-1.5 ATA.O2 series in 10 cases; and Rest-2.5 ATA.O2-after HBO (1 ATA.air) series in 8 cases. CBF measurements commenced 5 to 10 minutes after fixing a mask for oxygen inhalation. Arterial blood gas analyses using IL-813 (IL) and blood pressure measurements were done immediately after CBF measurements. CBF changes evaluated by ISI, estimating resting flow as 100% (PaO2: 93 +/- 8 mmHg), were 91% at 1 ATA.O2 50% (PaO2: 201 +/- 50 mmHg), 79% at 1 ATA.O2 (PaO2: 432 +/- 44 mmHg), 77% at 1.5 ATA.O2 (PaO2: 693 +/-79 mmHg) and 71% at 2 ATA.O2 (PaO2: 838 +/- 95 mmHg). CBF gradually decreased to the level shown for 2 ATA.O2, but CBF showed a tendency to increase somewhat at 2.5 ATA.O2 (81%, PaO2: 1103 +/- 111 mmHg). CBF decreases were statistically significant at 1 ATA.O2, 1.5 ATA.O2, 2 ATA.O2 and also 2.5 ATA.O2 compared with Rest (P less than 0.05). Arterial blood gas analyses clearly showed the stepwise increase in PaO2 to the level of 2.5 ATA.O2 (P less than 0.01). Changes in PaCO2 and blood pressure were slight and not significant statistically in each series. Since the data showed no significant change in the PaCO2 level in each series, it was concluded that the CBF decrease was due to vasoconstriction caused by the elevated PaO2. The mechanism of cerebral vasoconstriction caused by hyperoxemia is not yet clearly understood, but the direct vasoconstrictive effect of oxygen, neurogenic control and the metabolic effect of an elevated cerebral tissue oxygen level may contribute to the CBF decrease. CBF decrease during elevated PaO2 may be a protective physiological response to maintain normal brain metabolism and function against the excessive oxygen supply. Disturbance of this regulatory mechanism may result in oxygen poisoning of the central nervous system.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3098266 TI - Congenital heart disease in adults and adolescents. PMID- 3098267 TI - Interaction between thiopentone and sodium valproate. An in vitro and in vivo study. AB - The effect of sodium valproate on the binding of thiopentone to serum protein was studied in vitro. In the absence of valproate the unbound fraction of thiopentone was 15.2 +/- 0.64%, but with concentrations of valproic acid in excess of the therapeutic range, it increased to 22.42 +/- 1.65%. Scatchard plots for thiopentone in the absence and presence of valproate were investigated also. The barbiturate was bound by one group of binding sites with the association constant, Ka = 2.81 X 10(3) litre mol-1 and the number of binding sites (n) = 2.3. There was a marked decrease in this association constant in the presence of valproic acid (Ka = 1.82 X 10(3) litre mol-1), but without significant change in the number of binding sites (n = 2.13). Additionally, the effect of administration of sodium valproate i.v. on thiopentone anaesthesia was examined in rabbits. The recovery time from thiopentone was markedly longer in the presence of the anticonvulsant drug (17.0 min v. 37.1 min). PMID- 3098268 TI - Carbon dioxide clearance during high frequency jet ventilation. Effect of deadspace in a lung model. AB - The effects of the volume and length of deadspace on the clearance of carbon dioxide from a lung model have been investigated during high frequency jet ventilation (HFJV) at 1, 3 and 5 Hz. At 1 Hz, increasing the volume of the deadspace without changing the length caused a reduction in the clearance of carbon dioxide. At 5 Hz, an increase in the length of deadspace decreased carbon dioxide clearance, whilst an increase in volume had no effect. Since the delivered tidal volume was less than the volume of the morphological deadspace at this frequency, the elimination of carbon dioxide must have been accomplished by mechanisms which are not considered important at normal tidal volumes and frequencies. Furthermore, the clearance of carbon dioxide at 5 Hz was very inefficient compared with that at 1 Hz. It is concluded that, during HFJV, carbon dioxide is cleared most efficiently when the frequency is low enough for the delivered tidal volume to be greater than the volume of the morphological deadspace. PMID- 3098269 TI - Efferent phrenic nerve activity during induced changes in arterial pressure. AB - Efferent activity in the phrenic nerve was recorded during induced hypotension and hypertension in anaesthetized, paralysed, artificially ventilated dogs. Changes in arterial pressure were induced with infusions of sodium nitroprusside, noradrenaline and angiotensin II, after which ventilation was adjusted to return the PaCO2 near to control values. The PaO2 was maintained above chemoreceptor threshold throughout. When a steady state was achieved quantitative measurements of phrenic nerve activity were made. In six dogs an increase in mean arterial pressure from 114 to 167 mm Hg caused a mean reduction of phrenic nerve activity of 28%. In six dogs a decrease in mean arterial pressure from 128 to 82 mm Hg caused an increase in phrenic nerve activity of 22%. This shows that the reduction in arterial pressure induced by vasodilator drugs causes a major sustained stimulus to respiration, while increase in arterial pressure causes marked respiratory depression. PMID- 3098271 TI - Melatonin and cortisol increase after fluvoxamine. PMID- 3098270 TI - Does the benzodiazepine antagonist Ro 15-1788 antagonize the action of ethanol? AB - Ethanol aggravates benzodiazepine-induced central nervous depression by pharmacokinetic and/or pharmacodynamic interactions and Ro 15-1788 reverses promptly the hypnotic effects of benzodiazepines. We therefore studied the acute effects of Ro 15-1788 on the ethanol-induced sedation in six healthy male subjects. Subsequently to an oral loading dose (0.54 g ethanol kg-1) ethanol was infused for 4 h (0.15 g ethanol kg-1 h-1) and steady state blood levels between 0.9 to 1.2 g l-1 were reached within 2 h. At steady state and during the elimination phase of ethanol an intravenous bolus of 0.5 mg Ro 15-1788 or placebo was administered in a randomized, double-blind crossover fashion. The marked sedative effects of ethanol as assessed by visual analogue scales (2 to 6 fold increase in the sedation index), and choice reaction time (25 to 40% prolongation) were not affected by Ro 15-1788. However, the pharmaco-EEG indicated that Ro 15-1788 seems to reverse transiently the ethanol-induced changes in total alpha, delta, and slow alpha bands. There was no pharmacokinetic interaction between both agents since elimination of Ro 15-1788 (t1/2 = 1.2 +/- 0.7 h) and of ethanol (0.17 +/- 0.02 g l-1 h-1) were in good agreement with control values. Thus, it could be concluded that Ro 15-1788 might affect for a short while the action of ethanol by interfering with the benzodiazepine receptors. PMID- 3098272 TI - Effects of recombinant interferon-gamma and chemotherapy with isoniazid and rifampicin on infections of mouse peritoneal macrophages with Listeria monocytogenes and Mycobacterium microti in vitro. AB - The effect of recombinant murine interferon-gamma (IFN-gamma) on the growth of Listeria monocytogenes for 4 h and Mycobacterium microti for up to 3 days in monolayers of peritoneal macrophages from BALB/c mice was examined by serial viable counts of cell-associated bacteria. Macrophages pretreated with 10 u IFN gamma per ml were bacteriostatic and with 100 u or 1000 u per ml were bactericidal against L. monocytogenes. Addition of IFN-gamma 3 days before infection caused monolayers to be bactericidal against M. microti mainly during the first 15 min after infection. This was just evident with 10 u IFN-gamma per ml and greater with 100 u or 1000 u per ml. If IFN-gamma was added when phagocytosis of M. microti was complete, about 2 h after infection, its action was only bacteriostatic, the viable counts remaining stationary while those of unexposed monolayers increased. IFN-gamma 100 u per ml added before infection did not alter the bactericidal activity of rifampicin 10 mg/l, nor did it alter the killing curves for isoniazid 1 mg/l or for rifampicin 10 mg/l if added after completion of phagocytosis. PMID- 3098273 TI - Danazol fails to increase factor VIII or IX levels in a double-blind crossover study of patients with haemophilia A and B. AB - Twenty-one patients, 14 with haemophilia A and seven with haemophilia B, completed a double-blind crossover study to evaluate the effects of danazol on factor VIII and factor IX levels. Clotting and immunoradiometric assays were used to measure factor levels at baseline, 2 weeks and 8 weeks on both danazol and placebo. Fibrinogen, plasminogen and activated partial thromboplastin time were measured on all patients during placebo and danazol treatment. Although plasminogen levels rose significantly (P less than 0.01) and fibrinogen decreased (P less than 0.01), factor VIII and IX levels did not change. While on danazol, three patients had increased bleeding and shortened euglobulin lysis times compared to their baseline levels. We conclude that danazol does not raise factor VIII or IX levels and increases bleeding in some patients. PMID- 3098274 TI - Binding of thrombin-activated human factor VIII to platelets. AB - To study association of platelets with factor VIII, the purified protein was 125I labelled with Bolton-Hunter reagent to a specific activity of 243,000-360,000 cpm/U. Autoradiographs of SDS polyacrylamide gels revealed polypeptides of VIII at Mr about 240 kDa, 90 kDa and intermediate values, as well as some radioactive contaminants, but the light chain (Mr 78/76) seen with silver stain was not labelled. After 2.5-5-fold activation with thrombin, the higher radioactive Mr band disappeared, the band at 90 kDa became more intense, and a band appeared at about 45 kDa. The radioactivity associated with platelets, studied in the presence of haemophilic BaSO4-treated plasma, was maximal after 6-8 min and increased 3-15-fold on activation with thrombin. With activated VIII, autoradiographs of platelet pellets showed only VIIIa but results are expressed as units of unactivated VIII bound. At 0.3-0-0.7 U/ml, 10(8) platelets bound 0.0008-0.004 U VIIIa. The amount bound was not affected by the ratio of unlabelled VIII to VIII labelled in the presence of a 50-fold molar excess of unlabelled Bolton-Hunter reagent. Binding increased to 1.5 U VIIIa/10(8) platelets (about 13,600 molecules per platelet) at 140 U/ml, with no evidence of saturation. Binding was not affected by monoclonal antibodies to platelet glycoproteins IIb/IIIa or Ib, quenching the thrombin before adding platelets, or aggregating the platelets with A23187 in the presence of thrombin. Qualitatively, binding of labelled VIIIa and factor Va studied by others are similar. Binding of 125I-VIIIa to aggregated and unaggregated platelets was normal in patient M.S. whose platelets were shown by others to be deficient in their ability to bind radiolabelled factor Xa and generate coagulant activity. This difference. and the fact that platelet coagulant activity is increased by platelet activation and/or aggregation, suggest that binding of Va or VIIIa alone does not determine the assembly of active proteolytic complexes on the platelet surface. PMID- 3098275 TI - The significance of anti-c alloimmunization in pregnancy. AB - In an 8-year period, 177 of 280,000 pregnancies were complicated by maternal anti c alloimmunization. Although there was one neonatal death associated with anti-c haemolytic disease of the newborn, only two infants were severely anaemic at birth. A total of 11 babies required exchange transfusion, but nine of these developed hyperbilirubinaemia alone. The remaining c positive infants were either unaffected or only mildly affected by erythroblastosis fetalis. A strategy for management of these pregnancies is outlined, and proposed methods of prevention and serological control are discussed. PMID- 3098276 TI - Ketoacidosis in pregnancy: an unusual presentation of diabetes mellitus. Case reports. PMID- 3098277 TI - Comparison of K-Sol and M-K medium for cornea storage: results of penetrating keratoplasty in rabbits. AB - Five pairs of rabbit corneas were stored for two weeks at 4 degrees C, one of each pair in K-Sol medium, and one in McCarey-/Kaufman (M-K) medium. After transplantation all penetrating keratoplasty grafts became clear and thin. Endothelial cell loss was significantly less in the K-Sol stored corneas. Another five pairs of corneas were stored for two weeks in K-Sol or three days in M-K medium. After penetrating keratoplasty there were no significant differences in clarity, thickness, or endothelial cell loss. The results indicate that K-Sol provides satisfactory medium-term corneal storage compared with short-term storage in M-K medium at refrigerator temperatures. PMID- 3098278 TI - Diverticulum of the lacrimal sac associated with rhinosporidiosis. AB - A rare case of diverticulum of the lacrimal sac associated with rhinosporidiosis is reported. The clinical presentation and possible pathogenesis are discussed. PMID- 3098279 TI - Gonococcal conjunctivitis. PMID- 3098280 TI - An RNA polymerase mutant with reduced accuracy of chain elongation. AB - A new Escherichia coli RNA polymerase mutant was isolated which exhibited reduced accuracy of chain elongation in vivo and in vitro. The novel isolation procedure consisted of simultaneous selection for rifampicin resistance and screening for increased leakiness of an early, strongly polar nonsense mutation of lacZ, one of a special class of mutations whose leakiness reflects mainly transcriptional rather than translational errors. The spontaneous mutant thus isolated displayed a 3-4-fold increase in the leakiness of two different lacZ mutations of this class. Transduction analysis indicated that a single mutation, mapping in or very near the rpoB gene for the beta subunit of RNA polymerase, conferred both rifampicin resistance and increased nonsense leakiness. In an in vitro fidelity assay, homogeneous RNA polymerases from the mutant and parent strains exhibited error rates of 1/0.90 X 10(5) and 1/2.0 X 10(5), respectively, for the poly[d(A T)] X poly[d(A-T)]-directed misincorporation of noncomplementary GMP. These error rates were verified by product analyses which further revealed that GMP was misincorporated in place of AMP in the synthesis of poly[r(A-U)]. The error rate of wild-type K12 RNA polymerase from a different source was 1/2.0 X 10(5), while that of a hybrid RNA polymerase, containing mutant core enzyme and wild-type sigma subunit, was 1/0.64 X 10(5). These error rates confirmed the selection of a transcriptional accuracy mutant. The error frequencies observed are much lower than those reported in other in vitro assays. The safeguards used to avoid artifactually enhanced misincorporation, and to thereby quantitate lower error rates, are discussed. PMID- 3098281 TI - Peptide models of electrostatic interactions in proteins: NMR studies on two beta turn tetrapeptides containing Asp-His and Asp-Lys salt bridges. AB - Two model peptides Boc-Asp-Pro-Aib-X-NHMe [X = His (1) and X = Lys (2)] were synthesized to simulate intramolecular electrostatic interactions between ionizable side chains. Conformational analysis by 270-MHz 1H NMR in (CD3)2SO reveals that the backbone secondary structures of these two peptides are stabilized by two strong intramolecular hydrogen bonds, involving the consecutive carboxy-terminal NH groups. 1H NMR chemical shifts were measured in 1, 2, and a protected derivative, Boc-Asp(OBzl)-Pro-Aib-His-NHMe (3). These shifts were also measured for the model compounds Ac-Lys-NHMe, Boc-Asp-NHMe, and Boc-His-NHMe in their different states of ionization. An analysis of the chemical shifts of the ionization-sensitive reporter resonances suggests the formation of a strong intramolecular salt bridge in the lysyl peptide 2 and a bridge of moderate strength in the histidyl peptide 1. A comparison of the temperature dependence of chemical shifts in peptides 1-3 suggests that intramolecular salt bridge formation results in diminished backbone flexibility. The results establish that proximity effects confer far greater stability to intramolecular ion pair interactions vis-a-vis their intermolecular counterparts. The salt bridge interaction in peptide 1 displays a remarkable sensitivity to the dielectric constant of the solvent medium. The results suggest that these peptides are good simulators of the role of salt bridges in the structural dynamics of proteins. PMID- 3098282 TI - Isolation and characterization of a lectin from the cortical granules of Xenopus laevis eggs. AB - A cortical granule lectin was isolated from eggs of the South African clawed toad Xenopus laevis. The lectin was released from the cortical granules by activation of dejellied eggs with the Ca2+ ionophore A23187. The lectin was purified by affinity chromatography with its natural ligand, the egg jelly coat, chemically coupled to a Sepharose matrix. The purified lectin was homogeneous by the criteria of isoelectric focusing (pI = 4.6), immunodiffusion, and immunoelectrophoresis but existed in two different molecular weight isomers as determined by sedimentation velocity ultracentrifugation and disc gel electrophoresis. Molecular weights of the isomers were determined by ultracentrifugation, disc gel electrophoresis, and gel filtration and found to be 539,000 and 655,000. Chemically, the lectin was a metalloglycoprotein, composed of 84.0% protein, 15.8% carbohydrate, and 0.19% calcium. No unusual types or amounts of amino acids were present. The carbohydrate moiety was composed of fucose, mannose, galactose, glucosamine, galactosamine, and sialic acid. The monosaccharide specificity of the lectin was investigated with the sugar inhibition of the precipitin reaction in gels. The lectin was specific for D galactosyl sugars with the configuration at carbon atoms 2-4 of primary importance. PMID- 3098283 TI - Pyruvate dehydrogenase and 3-fluoropyruvate: chemical competence of 2 acetylthiamin pyrophosphate as an acetyl group donor to dihydrolipoamide. AB - The pyruvate dehydrogenase component (E1) of the pyruvate dehydrogenase complex catalyzes the decomposition of 3-fluoropyruvate to CO2, fluoride anion, and acetate. Acetylthiamin pyrophosphate (acetyl-TPP) is an intermediate in this reaction. Incubation of the pyruvate dehydrogenase complex with 3-fluoro[1,2 14C]pyruvate, TPP, coenzyme A (CoASH), and either NADH or pyruvate as reducing systems leads to the formation of [14C]acetyl-CoA. In this reaction the acetyl group of acetyl-TPP is partitioned by transfer to both CoASH (87 +/- 2%) and water (13 +/- 2%). When the E1 component is incubated with 3-fluoro[1,2 14C]pyruvate, TPP, and dihydrolipoamide, [14C]acetyldihydrolipoamide is produced. The formation of [14C]acetyldihydrolipoamide was examined as a function of dihydrolipoamide concentration (0.25-16 mM). A plot of the extent of acetyl group partitioning to dihydrolipoamide as a function of 1/[dihydrolipoamide] showed 95 +/- 2% acetyl group transfer to dihydrolipoamide when dihydrolipoamide concentration was extrapolated to infinity. It is concluded that acetyl-TPP is chemically competent as an intermediate for the pyruvate dehydrogenase complex catalyzed oxidative decarboxylation of pyruvate. PMID- 3098284 TI - Protein dynamics of glycogen phosphorylase. AB - The glycogen phosphorylase molecule absorbs the ultraviolet energy of a nitrogen laser to form an excited state of the cofactor. The decay rate of this state has a lifetime of 6.7 microseconds, and its sensitivity to bound substrates presents a new perspective of the mechanism. A careful analysis of the decay curve for native enzyme and cofactor analogues showed that the lifetime depends on the conformation of protein groups at the active site and how the residues change with bound substrate. The reactive ternary complexes obtained from either direction of the reaction yielded the same lifetime, indicating a change in the active-site conformation to a common configuration for the cofactor and substrate phosphate. This configuration indicates an increase in the cofactor 5'-PO4 pKa and a possible proton shuttle. The pyridoxal 5'-pyrophosphate reconstituted enzyme showed no conformational change alone or in the presence of oligosaccharide. This result does not support an electrophilic attack by the 5' PO4 phosphorus. PMID- 3098285 TI - Spectroscopic and equilibrium properties of the indoleamine 2,3-dioxygenase tryptophan-O2 ternary complex and of analogous enzyme derivatives. Tryptophan binding to ferrous enzyme adducts with dioxygen, nitric oxide, and carbon monoxide. AB - The dioxygen adduct of the heme protein indoleamine 2,3-dioxygenase has been generated at -30 degrees C in mixed solvents, and spectroscopic and equilibrium studies of its L-tryptophan (substrate) binding properties have been carried out for the first time. Comparative studies have also been performed with the NO and CO adducts of the ferrous enzyme. Under the conditions employed (-30 degrees C), both autoxidation and turnover (L-tryptophan + O2----formylkynurenine) of the ternary complex are effectively suppressed. Structural identification of the ternary complex is based on the 1:1 molar stoichiometry for the substrate oxygenated enzyme adduct formation (Kd approximately 10(-4) M), the time dependent linear product formation (turnover) at -20 degrees C, and the quantitative conversion of the complex to the ferrous CO derivative by bubbling with CO. Binding of L-tryptophan to the oxygenated enzyme leads to decreases in the intensities of its major absorption bands (lambda max 415, 541, 576 nm) and to a blue shift of its Soret peak. Interestingly, among the ferrous enzyme derivatives examined, only the substrate-bound oxygenated enzyme exhibits solvent dependent Soret absorption peak positions, e.g., lambda max 411.5 and 413.5 nm in 65% (v/v) aqueous glycerol and ethylene glycol, respectively. In addition, indole binds to the oxygenated enzyme, causing a red shift of its Soret peak in these solvents only in the presence of substrate (411.5----414 nm and 413.5----414.5 nm, respectively), while similar effects of indole are independent of tryptophan for the other ferrous enzyme derivatives.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098286 TI - hsp108,,,,,, a novel heat shock inducible protein of chicken. AB - cDNA clones encoding a protein that copurifies with the progesterone receptor B subunit but does not bind progesterone have been described [Kulomaa, M. S., Weigel, N. L., Kleinsek, D. A., Beattie, W. G., Conneely, O. M., March, C., Zarucki-Schulz, T., Schrader, W. T., & O'Malley, B. W. (1986) Biochemistry (preceding paper in this issue)]. A full-length sequence for these clones was derived and was found to encode a protein that is structurally unrelated to the progesterone receptor but that contains significant homologies to the previously described heat shock proteins hsp90 of yeast and hsp83a of Drosophila melanogaster. In this paper it is shown that this protein is indeed a heat shock protein. Though the apparent molecular weight of the protein is 108,000 on sodium dodecyl sulfate-polyacrylamide gels, the molecular weight of the polypeptide backbone is 92,000. The steady-state level of gene transcripts as well as the level of protein is inducible by heat shock, but the gene is constitutively expressed in a number of tissues. A previously undescribed heat shock protein of molecular weight 78,000 in these preparations is also reported. PMID- 3098287 TI - Inactivation of plasminogen activator inhibitor by oxidants. AB - The rapidly acting plasminogen activator inhibitor (PAI) purified from cultured bovine aortic endothelial cells (BAEs) was inactivated during iodination with chloramine T and other oxidizing iodination systems. Inactivation was observed in the absence of iodine, suggesting that the loss of activity resulted from the oxidizing conditions employed. In an attempt to further study the nature of this inactivation, the PAI was treated with chloramine T under conditions that specifically oxidize methionine and cysteine residues. Both PAI inhibitory activity and the ability of the PAI to form complexes with tissue-type PA were decreased in a dose-dependent manner by such treatment. The PAI was more sensitive to oxidative inactivation than urokinase, elastase, and alpha 1 protease inhibitor. Incubation of the chloramine T inactivated PAI with methionine sulfoxide peptide reductase in the presence of dithiothreitol (DTT) restored more than 90% of the PAI activity. The reductase is a DTT-dependent enzyme that specifically converts methionine sulfoxide to methionine. Little activity was restored by either the reductase or DTT alone. These results indicate that the oxidation of at least one critical methionine residue is responsible for the loss of PAI activity upon iodination. In this respect, the BAE PAI resembles alpha 1-protease inhibitor, a well-characterized elastase inhibitor that also is inactivated by oxidants. Both inhibitors are members of the serine protease inhibitor superfamily (Serpins), and both have a methionine residue in their reactive center. PMID- 3098288 TI - Streptococcal phosphoenolpyruvate-sugar phosphotransferase system: amino acid sequence and site of ATP-dependent phosphorylation of HPr. AB - The amino acid sequence of histidine-containing protein (HPr) from Streptococcus faecalis has been determined by direct Edman degradation of intact HPr and by amino acid sequence analysis of tryptic peptides, V8 proteolytic peptides, thermolytic peptides, and cyanogen bromide cleavage products. HPr from S. faecalis was found to contain 89 amino acid residues, corresponding to a molecular weight of 9438. The amino acid sequence of HPr from S. faecalis shows extended homology to the primary structure of HPr proteins from other bacteria. Besides the phosphoenolpyruvate-dependent phosphorylation of a histidyl residue in HPr, catalyzed by enzyme I of the bacterial phosphotransferase system, HPr was also found to be phosphorylated at a seryl residue in an ATP-dependent protein kinase catalyzed reaction [Deutscher, J., & Saier, M. H., Jr. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 6790-6794]. The site of ATP-dependent phosphorylation in HPr of S. faecalis has now been determined. [32P]P-Ser-HPr was digested with three different proteases, and in each case, a single labeled peptide was isolated. Following digestion with subtilisin, we obtained a peptide with the sequence -(P)Ser-Ile-Met-. Using chymotrypsin, we isolated a peptide with the sequence -Ser-Val-Asn-Leu-Lys-(P)Ser-Ile-Met-Gly-Val-Met-. The longest labeled peptide was obtained with V8 staphylococcal protease. According to amino acid analysis, this peptide contained 36 out of the 89 amino acid residues of HPr. The following sequence of 12 amino acid residues of the V8 peptide was determined: Tyr-Lys-Gly-Lys-Ser-Val-Asn-Leu-Lys-(P)Ser-Ile-Met-.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098289 TI - Conformational analysis of thymidylate synthase from amino acid sequence and circular dichroism. AB - Circular dichroism studies were carried out in the vacuum ultraviolet region for thymidylate synthase from Lactobacillus casei and its ligand complexes. The CD spectrum was analyzed for secondary structure by our method and the variable selection method, and both gave similar results. Our method predicts 33% alpha helix, 25% (23% antiparallel and 2% parallel) beta-sheet, 20% turns, and 16% other structure. The secondary structure of this protein was also predicted from the amino acid sequence by four different methods. Though there is a variation in the prediction among these methods, the prediction of 32% alpha-helix and 23% beta-sheet by combining the four methods is in excellent agreement with our CD results. Further, the location of the predicted regions of alpha-helices and beta strands along the sequence and the CD characteristics strongly suggest that this protein belongs to an alpha + beta structural class. Binding of the inhibitor FdUMP or the cofactor 5,10-methylenetetrahydrofolate did not change the CD spectrum. However, when both ligands were present, there was a significant change in the CD spectrum and the maximum changes occurred when the concentration of FdUMP was 1 mol/mol of enzyme. The addition of FdUMP and cofactor causes, respectively, a 5% and 6% decrease in beta-sheet and beta-turns and about an 8% increase in "other" structure. PMID- 3098290 TI - Characterization of the phosphoserine of pepsinogen using 31P nuclear magnetic resonance: corroboration of X-ray crystallographic results. AB - The endogenous phosphoserine residue in porcine pepsinogen has been titrated with use of phosphorus-31 nuclear magnetic resonance (31P NMR). It has an observed pKa2 of 6.7 and a narrow line width (congruent to 10 Hz). The phosphate can be readily removed by an acid phosphatase from potato; however, it is resistant to hydrolysis by several alkaline phosphatases. The X-ray crystal structure of porcine pepsinogen at 1.8-A resolution [James, M. N. G., & Sielecki, A. (1986) Nature (London) 319, 33-38] shows a rather weak and diffuse region of electron density in the vicinity of the phosphorylated serine residue. This suggests considerable dynamic mobility or conformational disorder of the phosphate. In order to define more fully this behavior, the NMR data have been used to corroborate these crystallographic results. All these physical data are consistent with a highly mobile phosphoserine residue on the surface of the zymogen and freely exposed to solvent. In addition, certain properties of this phosphoserine moiety on pepsinogen are similar to those of one of the phosphorylated residues of ovalbumin. The possible significance of this is discussed. PMID- 3098291 TI - Assessment of binding of L-cystine and L-lysine by rat renal brush-border membranes. AB - Cystine and lysine bind to isolated rat renal brush-border vesicles. Three methods to determine the extent of amino acid binding to the membranes have been compared, one relying on the osmotic reactivity of the vesicle, a second by trichloroacetic acid precipitation of membrane-bound material and a third by initial rate analysis. For cystine, all methods yield comparable results at early time points, indicating the trichloroacetic acid method is a simple and valuable tool for binding estimation under initial-rate or near initial-rate conditions. For lysine, initial rate analysis and osmotic perturbation are the methods of choice since lysine co-precipitates with trichloroacetic acid. PMID- 3098292 TI - The maturational breakdown of mitochondria in reticulocytes. PMID- 3098293 TI - DNA methyltransferase polypeptides in mouse and human cells. AB - DNA methyltransferase was isolated as a single polypeptide of 190 kDa from mouse P815 mastocytoma cells by immunoaffinity chromatography. This polypeptide seems to be highly susceptible to proteolytic degradation resulting in additional polypeptides in the size range of 150 to 190 kDa. A polypeptide of 190 kDa was immunoprecipitated by monoclonal anti-DNA methyltransferase antibodies from extracts of two different human cell lines, Raji and K562. The 190 kDa polypeptide was synthesized in rapidly proliferating cells and, albeit at a much lower rate, also in cells grown to saturating density. DNA methyltransferase polypeptides smaller than 190 kDa were synthesized neither in log phase nor in stationary phase cells. PMID- 3098294 TI - Properties of two unusual, and fluorescent, substrates of purine-nucleoside phosphorylase: 7-methylguanosine and 7-methylinosine. AB - The properties of two unusual substrates of calf spleen purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1), 7-methylguanosine and 7-methylinosine, are described. The corresponding bases, 7 methylguanine and 7-methylhypoxanthine, are neither substrates in the reverse, synthetic reaction, nor inhibitors of the phosphorolysis reaction. Both nucleosides exhibit fluorescence, which disappears on cleavage of the glycosidic bond, providing a new convenient procedure for continuous fluorimetric assay of enzymatic activity. For 7-methylguanosine at neutral pH and 25 degrees C, Vmax = 3.3 mumol/min per unit enzyme and Km = 14.7 microM, so that Vmax/Km = 22 X 10( 2)/min per unit as compared to 8 X 10(-2) for the commonly used substrate inosine. The permissible initial substrate concentration range is 5-100 microM. Enzyme activity may also be monitored spectrophotometrically. For 7 methylinosine, Vmax/Km is much lower, 2.4 X 10(-2), but its 10-fold higher fluorescence partially compensates for this, and permits the use of initial substrate concentrations in the range 1-500 microM. At neutral pH both substrates are mixtures of cationic and zwitterionic forms. Measurements of pH-dependence of kinetic constants indicated that the cationic forms are the preferred substrates, whereas the monoanion of inosine appears to be almost as good a substrate as the neutral form. With 7-methylguanosine as substrate, and monitoring of activity fluorimetrically and spectrophotometrically, inhibition constants were measured for several known inhibitors, and the results compared with those obtained with inosine as substrate, and with results reported for the enzyme from other sources. PMID- 3098295 TI - The mobility of concanavalin A receptors and surface immunoglobulins on rat hepatocyte plasma membranes. AB - Lateral mobilities of lectin receptors and surface immunoglobulins were measured in plasma membranes of hepatocytes prepared by smearing small pieces of rat liver tissue and then using the fluorescence recovery after photobleaching (FRAP) technique. Smears were treated with various doses of fluorescein isothiocyanate (FITC) conjugated concanavalin A (ConA), succinylated ConA (SConA), wheat germ agglutinin (WGA), and soybean agglutinin (SBA), as well as with rabbit anti-rat IgG (RARa/IgG) and goat anti-rat IgM(Fc) (GARa/IgM(Fc] antisera. 10 micrograms/ml ConA and SConA concentrations and a 55 X dilution of the GARa/IgM(Fc) antiserum were found to be suitable for measuring the lateral mobilities dependent on age. Diffusion constant and mobile fractions of receptor complexes were measured in different age groups of female Fisher rats (from 1 to 26 month-old). The FRAP measurements revealed that at least two major receptor sites can be distinguished in cell membranes of compact tissue (similar to the cultured and isolated cells), forming a mobile and an immobile fraction. The mobile fractions of both the lectin receptors and the surface immunoglobulins tended to decrease with age, while the age differences of the diffusion constants were not statistically significant. The observed alterations could be due to the covalent crosslinking of the mobile receptors to immobile patches and/or to the retardation of free diffusion by the cytoskeleton, dependent on age. PMID- 3098296 TI - Functional differentiation of amphiphilic helices of the apolipoproteins by hydrophobic moment analysis. AB - The amphiphilic character of different plasma apolipoproteins was investigated by a combination of established hydrophobicity analysis methods. These methods proved to be powerful in the detection of amphiphilic phospholipid-binding domains. Within this class of lipid-binding domains, lecithin-cholesterol acyltransferase activating and non-activating helices could be differentiated by calculating hydrophobic moments at different angles. We conclude that the hydrophobic characteristics of the different helices determined the mode of lipid binding and the substrate properties of these phospholipid-protein complexes for the lecithin-cholesterol acyltransferase reaction. PMID- 3098297 TI - Metabolic activities in human skin fibroblasts preloaded with labeled GM2 ganglioside. AB - Confluent cultures of human skin fibroblasts were maintained for 10 days with sphingosine labeled [3H]GM2. Labeled medium was then replaced with normal medium and the cells maintained for 42 days with weekly medium changes. Cells were harvested at regular intervals and cells, medium, and trypsin digest supernatant analyzed for [3H]GM2 and its metabolic products. The ganglioside can be membrane associated and removed by trypsin, or membrane incorporated and trypsin insensitive. The membrane incorporated material is apparently transported to the lysosomes slowly by membrane flow, where 80% of the cellular GM2 can be metabolized by day 42. [3H]GM2 as well as its metabolic products in control cells is continuously released into the medium, during which it can also become associated with the cell surface membrane. There is no detectable metabolism of the [3H]GM2 in GM2 gangliosidosis cell lines over the extended post-labeling period, indicating that there is no residual enzyme activity in these cells. Undegraded GM2 is continuously released into the medium and remains associated with the cell surface membrane as well. PMID- 3098298 TI - Incorporation of arachidonic acid into 1-acyl-2-lyso-sn-glycero-3-phosphocholine of the human neutrophil. AB - In this study, the initial incorporation of arachidonic acid into human neutrophils has been examined. Neutrophils pulse labeled for 5 min with [3H]arachidonic acid rapidly incorporated this fatty acid into 1,2 diacylglycerophosphocholine. However, when neutrophils were pulse labeled with [3H]arachidonic acid for 5 min, washed, and allowed to incubate for an additional 120 min, the relative amount of [3H]arachidonic acid increased in alkylacylglycerophosphocholine molecular species. Similar, when neutrophils were pulse labeled, washed, and allowed to incubate in the presence of 30 microM unlabeled arachidonic acid for 120 min, [3H]arachidonic acid was also remodeled into alkylacylglycerophosphocholine. These results implied that the initial incorporation of [3H]arachidonic acid proceeded via a free fatty acid intermediate into 1,2-diacyl-GPC, while the subsequent remodeling of arachidonate containing glycerophospholipids did not. This initial incorporation was further investigated in a number of cell-free systems. Disrupted neutrophils incubated with [14C]arachidonoyl-CoA incorporated [14C]arachidonic acid into 1,2-diacyl-GPC containing 16:0, 18:0, and 18:1 at their sn-1 position in a pattern similar to that seen when whole neutrophils were incubated with arachidonic acid for 5 min. A small percentage of [14C]arachidonate from [14C]arachidonoyl-CoA was incorporated into 1-alkyl-2-acyl-GPC. The enzymatic activity responsible was found predominately in the membrane fraction of the broken cell preparation. This selectivity of the CoA-dependent acyltransferase for 1-acyl-linked glycerophosphocholine was further examined by adding [14C]arachidonoyl-CoA and various 1-radyl-2-lyso-GPC to neutrophil membrane preparations. These studies provide evidence that the initial incorporation of arachidonic acid into sn glycero-3-phosphocholine takes place by an arachidonoyl-CoA: lysophosphatidylcholine acyltransferase(s) which is selective for the 1-acyl-2 lyso-GPC. PMID- 3098299 TI - Synthesis of purines in human lymphoblast cells deficient in methylthioadenosine phosphorylase activity. AB - Two human lymphoblastic cell lines, deficient in methylthioadenosine phosphorylase (MTAP) activity, were found to have increased rates of de novo purine synthesis. These MTAP- cell lines were K562, an undifferentiated leukemic line and CCRF-CEM, a leukemic line of T-cell origin. Another T-cell line, CCRF HSB-2 was found to be deficient in activity. However, this line did not demonstrate elevated rates of purine synthesis. Purine metabolism in the above cell cultures was compared with MTAP+ human B-cell lines and two human T-cell lines (MOLT-3 and MOLT-4). In all the MTAP+ cell lines, the rate of de novo purine synthesis was inhibited by the presence of methylthioadenosine in the assay medium (10 microM concentration produced more than 90% inhibition). However, purine synthesis in the MTAP- cells was resistant to inhibition by methylthioadenosine. Adenine in the assay medium inhibited de novo purine synthesis in MTAP+ and MTAP- cells to a similar degree. This inhibition was dose dependent and was elicited by concentrations similar to those of methylthioadenosine. Growth of the cell lines in culture was not affected by either methylthioadenosine or adenine at the concentrations which produced inhibition of purine synthesis. These results suggest that purine synthesis in MTAP+ cells is inhibited by adenine formed from the phosphorolytic cleavage of methylthioadenosine by methylthioadenosine phosphorylase. PMID- 3098300 TI - Interleukin-1-like factor (mononuclear cell factor) modulates proteoglycan synthesis in cultured human synovial cells. AB - Cultured human synovial cells treated with an interleukin-1-like mononuclear cell factor incorporated more 35S in proteoglycans than control cultures, but the radioactivity distribution between medium and cell layer was not modified. Proteoglycans were synthesized essentially in monomeric form and the mononuclear cell factor increased the molecular weight of these monomers. The [3H]hexosamine/[14C]serine ratio in purified proteoglycans on the one hand, and the study of [35S]glycosaminoglycan molecular weight, on the other hand, indicated that this increase is not modulated through enhanced synthesis of core protein but by an increase in the glycosaminoglycan chain length. After enzyme hydrolysis, dermatan sulfate (62% of the total glycosaminoglycans) and chondroitin 4/6-sulfate (30%) were found to be the major glycosaminoglycans synthesized by cultured synovial cells, and the existence of 8% heparan sulfate was evidenced by nitrous acid treatment. In the presence of the mononuclear cell factor, the dermatan sulfate synthesis was decreased (47%), with a concomitant increase of chondroitin sulfate synthesis (45%). PMID- 3098301 TI - An investigation of fibrin-platelet adhesive interactions by microfluorimetry. AB - Interactions between human blood platelets and fibrin have been visualized by light microscopy, and quantitative details of the extent, rate and specificity of fibrin-platelet binding obtained by microfluorimetry. Adhesion of fluorescein labelled fibrin to activated platelets yielded brightly fluorescent fibrin platelet aggregates, which emitted light at an intensity 4-7-fold greater than that due to nonspecific association of fluorescein-fibrin with unstimulated fixed cells. The intensity of fluorescent light emitted from fibrin-platelet aggregates increased as a function of time, reaching a plateau after about 1 h under physiological buffer and temperature conditions. Two monoclonal antibodies directed against the glycoprotein IIb-IIIa complex, which have been shown to inhibit the binding of fibrinogen and soluble fibrin oligomers to ADP-stimulated platelets, were employed to further probe the specificity of this adhesive interaction. In contrast to the results with the soluble ligands, one of these antibodies (HP1-1D) was capable of fully inhibiting the attachment of fluorescent fibrin to ADP-activated cells while the other (AP-2) was much less effective. PMID- 3098302 TI - The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations. AB - We have studied the activation of human blood platelets by the inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin. The effect of thapsigargin was compared with other common agonists (calcium ionophore A23187, phorbol ester TPA and thrombin). Platelet aggregation, serotonin release, raised cytoplasmic free calcium level and phosphorylation of platelet proteins was examined in platelet-rich plasma and washed platelet suspension. In contrast to A23187 and thrombin, the platelet activation induced by thapsigargin developed slowly, with maximal response obtained after 2-3 min. Both the thapsigargin- and the A23187 induced serotonin releases were synergistically increased by TPA. Studies of the phosphorylation of platelet proteins revealed that thapsigargin and A23187 equally well induced a selective phosphorylation of two proteins with apparent molecular masses of 20 kDa and 47 kDa. These proteins, which are substrates of myosin light-chain kinase and protein kinase C respectively, are known to be involved in platelet activation. The thapsigargin-induced platelet aggregation and serotonin release was completely inhibited by class I (nimodipine), class II (verapamil) and class III (diltiazem) calcium-channel blockers. The inhibitory activity of nimodipine was abolished by the corresponding 1,4-dihydropyridine calcium-channel agonist, BAY K 8644. These results shows that the thapsigargin induced platelet activation is mediated by an increase in the cytoplasmic free calcium level, presumably obtained by stimulation of the passive calcium transport through specific channels. These thapsigargin-sensitive channels should predominantly be located in the membranes of intracellular calcium stores rather than in the plasma membrane, because removal of extracellular calcium by EGTA had only an insignificant effect on the thapsigargin-induced rise in cytoplasmic free calcium level. PMID- 3098303 TI - The phosphatidyl choline exchange properties in the cytosol of Aspergillus niger. AB - The presence of a PC-binding activity in the cytosol of Aspergillus niger van Tieghem has been established by measuring the reversible exchange of labeled DPC between an adsorbent (celite) and the cytosol. We have shown that this exchange is dependent upon the temperature and the ionic strength and it varies linearly with the protein concentration. This PC-binding activity is able to discriminate between DPC and some other phospholipids. PMID- 3098304 TI - Fatty acids and carbohydrate-containing lipids in four Micrococcaceae strains. AB - Fatty acid composition and lipidic carbohydrate to lipidic phosphorus molar ratio of yellow pigmented micrococci are compared to red pigmented ones and may be summarized by three indexes. These bacteria show wide differences in their fatty acid composition: three strains possess saturated branched chain fatty acids and one has unsaturated straight chain ones. A significant increase in 'anteiso/iso indexes' is observed between pink (M. roseus) and yellow colored bacteria (M. lysodeikticus, S. lutea). There is no significant difference (P greater than 0.05) between the 'unsaturation indexes' of the red pigmented parental D. radiodurans strain and its colorless mutant. Radioresistant strains exhibit a higher 'carbohydrate/phosphorus index' than other strains. There seems to be a relationship between a high carbohydrate-containing lipid content and a high resistance to physical and chemical agents, in particular to radiations. These differences observed in the lipid composition have implications in taxonomy and in establishing an evolutionary scheme. PMID- 3098305 TI - The shikimate pathway. V. Fluorine-containing analogues of 3-deoxy-D-arabino hept 2-ulosonate-7-phosphate (DAHP). AB - (3R) and (3S) 3-deoxy-3-fluoro-7-phospho-D-arabino hept-2-ulosonic acids (3R and 3S-3F-DAHP) the 3-fluoro analogues of DAHP were synthesized from the corresponding 2-deoxy-2-fluoro hexose-6-phosphates. 3R- and 3S-3F-DAHP were tested as substrates for 3-dehydroquinate synthetase from E. coli. Determination of kinetic parameters showed that their apparent Km and Vm were in the same order of magnitude for these two compounds. Further conversion of 3R- and 3S-3F-DAHP into (6R) and (6S) 6-fluoro dehydroshikimate and (6R) and (6S) 6-fluoro shikimate, respectively, was investigated and results are discussed. PMID- 3098306 TI - Purification and characterization of bolaffinine, a toxic protein from Boletus affinis Peck (Boletaceae). AB - A toxic protein of Mr 22,000, called bolaffinine, has been purified from the mushroom, Boletus affinis Peck (Boletaceae), with a 0.65% yield using a procedure involving four steps: ammonium sulfate precipitation, two chromatographies on ion exchange columns and gel filtration on Sephadex G-75. It is thermolabile and can be inactivated by organic solvents. Its isoelectric point lies between pH 9 and 10. It contains 234 amino acids, no free SH groups and one disulfide bridge as evidenced by reactions with 5-5'-dithiobis-nitrobenzoate (DTNB) and 2 mercaptoethanol. When injected into mice, it provokes the death of animals within 16-24 h. The 24 h LD50 is 61 mg/kg of body weight. Bolaffinine inhibits protein synthesis in hepatoma tissue culture and in a rabbit reticulocyte lysate. PMID- 3098307 TI - Purification and characterization of a toxin inhibiting protein synthesis from Croton mongue, a Madagascar Euphorbiaceae. AB - Monguine, a thermostable toxic protein was extracted from the seeds of Croton mongue (Euphorbiaceae) and purified by ion-exchange chromatography on DEAE cellulose and gel filtration on Sephadex G-25 and G-15. Polyacrylamide gel electrophoresis of purified monguine in the presence of sodium dodecyl sulfate and after treatment with 2-mercaptoethanol showed one band corresponding to a molecular weight of 9000. The same molecular weight was determined by analytical centrifugation. Amino acid analysis revealed a high content in both aspartic and glutamic acids (or the corresponding amides). The LD50 (24 h) is 12 mg/kg of mouse body weight. Monguine inhibits protein synthesis in hepatoma tissue culture cells and globin synthesis in a rabbit reticulocyte lysate. PMID- 3098309 TI - Studies on the kinetics of immobilized enzyme using a recycling enzyme reactor system. AB - A method of measuring kinetic parameters of immobilized enzyme with a recycling enzyme reactor system is described. By analyzing the plot of the dimensionless variable Ln(1-X)/X versus the time needed for a unit conversion, t/X, the mechanism of enzymatic reaction can be recognized and then its basic parameters can be evaluated. On the basis of the experimental data measured by P.R. Coulet et al., it has been proposed that the successive degradation of maltodextrins by the collagen membrane-bound amyloglucosidase was a product glucose inhibition reaction and their corresponding constants have been found with this method. PMID- 3098308 TI - Accumulation of dinucleoside polyphosphates in Saccharomyces cerevisiae under stress conditions. High levels are associated with cell death. AB - Adenosine tetraphosphonucleosides (Ap4X) were measured in Saccharomyces cerevisiae by a coupled phosphodiesterase-luciferase assay. After exposure of the cells to cadmium or to hyperthermic treatment (46 degrees C) a marked increase of the cellular pool from 0.08 microM (base level) to 4 microM or higher was observed. The accumulation of Ap4X to high levels is associated with irreversible processes leading to cell death. PMID- 3098311 TI - Lithium decreases 5-HT1 receptors but increases 5-HT-sensitive adenylate cyclase activity in rat hippocampus. AB - The effect of lithium (Li) treatment on serotonin1 (5-HT1) receptors and 5-HT sensitive adenylate cyclase (ACase) activity in rat hippocampus was studied. [3H]5-HT binding to 5-HT1 receptors was decreased after either subacute (5 days) or chronic (3 weeks) treatment. In contrast, 5-HT-stimulated [3H]cyclic adenosine monophosphate ([3H]cAMP) formation was unchanged after 5 days of Li treatment, but was increased after 3 weeks of treatment. There was no difference in the inhibitory effects of guanosine triphosphate (GTP) on [3H]5-HT binding between the subacute Li and control groups. In addition, [3H]cAMP formation induced by GTP was not changed in the subacute group, whereas chronic treatment decreased it. These results suggested that chronic Li treatment caused the facilitation of 5-HT-sensitive ACase activity in spite of a decrease in the density of 5-HT1 receptors in the hippocampus. The enhancement of the coupling between receptor and ACase seemed not to be involved in these Li effects. PMID- 3098310 TI - Intracellular pH control in Dictyostelium discoideum: a 31P-NMR analysis. AB - Phosphorus metabolites and intracellular pH have been examined in the slime mold Dictyostelium discoideum by non-destructive 31P-NMR measurements. In a spectrum from a suspension of aerobic amoebae, the major peaks are inorganic phosphate, nucleotide di- and triphosphates. In the corresponding perchloric acid extract, resonances originating from purine and pyrimidine nucleotides are resolved. Adenine nucleotides are the most abundant components, but the other nucleotides are present in significant amounts. In a spectrum from intact spores in a dormant state, only inorganic phosphate and polyphosphates are detected and nucleotides are no longer present in large amounts. Of particular importance is the ability to observe separately in aerobic amoebae the resonance of inorganic phosphate localized in two different cell compartments: the cytosol and the mitochondria. The cytosolic pH and mitochondrial pH have been measured as 6.7 and 7.7, respectively, on the basis of intracellular inorganic phosphate chemical shifts. They are essentially unaffected over a large range of external pH and they are not modified transiently or permanently during the initiation of the developmental program of the organism. A weak acid, such as propionate, which modifies the progression of differentiation by favoring prestalk cells, perturbs intracellular pH gradients by selectively decreasing mitochondrial pH without any effect on cytosolic pH. PMID- 3098312 TI - Effect of postnatal treatment with a gonadotropin-releasing hormone antagonist on sexual maturation of male rats. AB - The role of postnatal pituitary-testicular activity in sexual maturation at puberty was studied in male rats. Rats were injected twice daily with a potent gonadotropin-releasing hormone antagonist (N-Ac-4-Cl-D-Phe1, 4-Cl-D-Phe2, D-Trp3, D-Phe6, D-Ala10-NH2-GnRH) (GnRH-Ant.), 2 mg/kg, on Days 1-15 of life, and killed on Day 48, 56 or 90 of life. The treatment delayed the onset of puberty (monitored by balano-preputial separation) by 8 days (from the age of 48 to 56 days). The weights of testes, seminal vesicles and ventral prostates were reduced by 50-60% on days 48 and 56 of life, but only the testis weights remained suppressed by Day 90. Levels of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH), but not those of prolactin (Prl), were elevated 2-to-4 fold in the treated animals at the three ages studied. Serum and testicular testosterone (T) and the receptors for LH and Prl were suppressed in the peripubertal animals (48 and 56 days), but serum T was elevated and the receptor levels were normal in the 90-day group. The testicular FSH receptors were 50% suppressed at all ages studied. Only minor changes were observed in testicular histology when studied at 48 and 56 days. The 85-day-old animals treated with GnRH-Ant. were infertile when mated with females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098313 TI - Effects of food restriction and restoration on gonadotropin and growth hormone secretion in immature male rats. AB - This experiment concerned the changing patterns in secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and growth hormone (GH) under conditions of food restriction and subsequent catch-up growth. Weanling male rats were given either restricted (4 g food/day) or unrestricted access to food until 60 days of age. At this age, food-restricted rats weighed only 25% as much as rats fed ad libitum. Food restriction resulted in a dramatic decrease in the frequency of LH and GH pulses, and in the amplitude of GH pulses. It also slightly but significantly decreased mean blood levels of FSH (which was not secreted in a pulsatile manner in 60-day-old controls fed ad libitum). When restricted rats were given unrestricted access to food, frequency of LH and GH pulses and mean levels of FSH increased significantly and simultaneously within 2 days in half of the animals. Only an additional 8-10% of their body weight decrement was recovered at this time. After 10 days of food restoration, when restricted rats still weighed 50% less than controls, their secretory patterns of all three hormones were not significantly different from those of controls. Thus, recovery of gonadotropin and GH secretion was relatively rapid. Except for the quantitatively lesser impact of food restriction on FSH secretion, there was no evidence of any priorities in the secretion of the three hormones. Under conditions of rapid catch-up growth, the secretory patterns of LH, FSH, and GH appeared to develop simultaneously. PMID- 3098314 TI - Development of the polycystic ovarian condition (PCO) in the estradiol valerate treated rat. AB - A wide range of experimental manipulations results in an anovulatory polycystic ovarian (PCO) condition in the rat. Although PCO has been studied in a number of these models, research has centered on the condition after it is well established rather than as it develops. Consequently, it is still not clear exactly what follicular cysts are or how and why they form. Therefore, we studied the development of PCO in rats treated with estradiol-valerate (EV). In this model, definitive cysts were present 8-9 wk after a single injection of EV. Animals were killed at 5, 11, 16, 21, 28 and 56 days after EV treatment. Serum was assayed for luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Ovaries were weighed and prepared for histologic examination. The ovaries were serially sectioned such that the number and size distribution of normal and atretic follicles could be assessed quantitatively. Oviducts were examined for the presence of ova. Immediately after EV treatment, ovulatory cycles ceased; by 16 20 days posttreatment, all animals exhibited persistent vaginal cornification. Basal concentrations of serum LH and FSH fell to a nadir at 11 days posttreatment, after which both gonadotropins exhibited a trend toward recovery. Within the first 28 days after treatment, ovarian weights declined significantly as did the total number of healthy follicles. Atretic follicles of all sizes were particularly numerous at 16 days. By 28 days, the decline in the number of healthy follicles reached a plateau. Numerous atretic, large secondary follicles were particularly prominent on the background of the decreasing number of normal follicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098315 TI - Inactivation of follicle-stimulating hormone by a factor in a bovine serum albumin preparation. AB - Bovine serum albumin (BSA) preparations are commonly employed as "carrier" or "protective" proteins in the solutions used to dissolve gonadotropin preparations. The present report describes a BSA preparation that was found to contain a factor that inactivated follicle-stimulating hormone (FSH). Four different BSA preparations (designated BSA1, BSA2a, BSA2b, BSA3) were studied. The FSH preparation (NIH-FSH-S16) was dissolved in 0.15 M NaCl, containing the various BSA preparations. The FSH solutions were injected subcutaneously, twice daily, for 5 days into hypophysectomized immature female rats bearing estrogen capsules. Twenty-four hours after the last injection, the rats were decapitated, and the ovaries were removed, trimmed and weighed. The FSH preparation produced ovarian weight gain when BSA1, BSA2b, or BSA3 was used, but not when BSA2a was used in the vehicle. In animals injected with the FSH dissolved in BSA1 vehicle and injected at a separate site with BSA2a solution, the FSH preparation was fully active, which indicates that contact of the BSA2a preparation with FSH was required for the inactivating factor to be operant. Indeed, after incubation in BSA2a solution, the radiolabeled FSH preparation exhibited a slight decrease in apparent molecular size when chromatographed on a Sephadex G-100 column. This result suggests that the BSA2a preparation contained a factor that may have inhibited FSH by degrading it. PMID- 3098316 TI - Control of cytoplasmic calcium with photolabile tetracarboxylate 2 nitrobenzhydrol chelators. AB - This paper introduces nitr-2, a new Ca2+ chelator designed to release Ca2+ upon illumination with near UV (300-400 nm) light. Before illumination nitr-2 has Ca2+ dissociation constants of 160 and 630 nM in 0.1 and 0.3 M ionic strength respectively; after photoconversion to a nitrosobenzophenone the values shift to 7 and 18 microM, high enough to liberate substantial amounts of Ca2+ under intracellular conditions. The speed of release is limited by a dark reaction with rate constant 5 s-1. Aplysia central neurons injected with nitr-2 and exposed to UV light exhibit two separate Ca2+-dependent membrane currents: one carried by potassium ions and one a nonspecific cation current. A quantitative estimate of the spatial distribution of intracellular [Ca2+] changes in large cells filled with a high concentration of nitr-2 and exposed to an intense UV flash is offered. PMID- 3098317 TI - In vitro immune interferon induction during tumor evolution. AB - In a syngeneic C3H mammary adenocarcinoma model we studied gamma-interferon (gamma IFN) production during tumor evolution. The IFN production was induced by soluble tumor extracts on spleen cell cultures from tumor-bearing mice. A low level of IFN production was found in culture supernatants from small tumor bearing mice (tumor diameter less than 10 mm, 12-15 days of tumor evolution). In advanced stages of tumor growth (diameter more than 15 mm, 20 days or more of tumor evolution), this ability was lost. PMID- 3098318 TI - CNS-side effects induced by Ifosfamide-Mesna in children with osteosarcomas. AB - The authors have had the opportunity to see two cases of CNS side effects of Ifosfamide-Mesna association in children. Data in the medical literature about this subject remains poor. Only a few observations are available. In the referred cases, CNS side effects (lethargy, apathy and mutism) appeared a few hours after the second day of treatment and were spontaneously reversible in a few days. After reviewing possible mechanisms of this toxicity the authors pointed out the necessity to keep this type of side effects of Ifosfamide-Mesna association in mind, and to avoid it in susceptible patients. PMID- 3098320 TI - Characterization of a monoclonal antibody having selective reactivity with normal and neoplastic plasma cells. AB - A myeloma cell-reactive monoclonal antibody (MoAb), MM4, was generated from BALB/c mice immunized with alternate injections of cells from two human multiple myeloma (MM) cell lines. Screening by the enzyme-linked immunosorbent assay (ELISA) technique showed that MM4 reacted with human MM cell lines (7 of 7 positive), as well as bone marrow aspirates from MM patients (4 of 4 cases positive). MM4 did not react with marrow aspirates from control patients (3 cases), or with peripheral blood mononuclear (PBM) cells from normal subjects, lymphocytic (12 cases) and myelogenous (8 cases) leukemia patients. In addition, MM4 was negative with polymorphonuclear leukocytes and RBCs from normal donors. By means of the immunoperoxidase technique, the MM4-reactive antigen was detected in paraffin-embedded, Zenker formalin-fixed bone marrow biopsies of MM (12 of 12 cases positive), Waldenstrom's macroglobulinemia (2 of 2 cases positive), asymptomatic plasma cell dyscrasia (4 of 4 cases positive), and certain lymphomas (2 of 5 cases positive). Marrow biopsies from lymphocytic (5 cases) and myelogenous (5 cases) leukemias were uniformly negative. The MM4-reactive antigen also was expressed on plasma cells generated from pokeweed mitogen (PWM) stimulated normal PBM cultures. The pattern of reactivity of MM4 with lymphocytes of B origin was similar to that of the plasma cell MoAb PCA-1. Competitive binding studies showed, however, that these two MoAbs recognized distinct antigenic determinants. These observations suggest that MM4 may be useful for the study of human plasma cell dyscrasias. PMID- 3098319 TI - Cloning and characterization of platelet factor 4 cDNA derived from a human erythroleukemic cell line. AB - We report the isolation of a platelet factor 4 (PF4) cDNA clone from a lambda gt11 expression cDNA library which was derived from a human erythroleukemic (HEL) cell line. The sequence of the DNA insert includes the 3'-untranslated region, the entire amino acid coding region for the mature PF4 protein, and a 5' region containing coding information for an additional 18 amino acids. In addition, supplemental genomic DNA sequencing shows that the full-length leader sequence is 30 amino acids long plus an initial methionine and codes for a hydrophobic signal like sequence which is probably involved in transmembrane transport. A single species mRNA of approximately 800 nucleotides was detected on blots of HEL cell poly(A) + RNA using a labeled PF4 cDNA probe. The human PF4 leader sequence shares some DNA, but no amino acid, homology with the 15 amino acids at the N terminus of mature bovine PF4, suggesting rapid divergence in this region of PF4 between these two species. Sequence comparison of the coding regions of mature PF4 and gamma IP-10, a protein induced in a variety of cells following treatment with gamma-interferon, shows a corrected divergence of 76%. The divergence of a common ancestor protein into PF4 and gamma IP-10 may have accompanied the development of sophisticated immune and coagulation systems in vertebrates. The availability of cDNA and genomic DNA information for these genes in other species will be useful in studying the evolution of the coagulation and immune systems. PMID- 3098321 TI - In vitro regulation of human hematopoiesis by natural killer cells: analysis at a clonal level. AB - We studied the effects of a series of well-characterized clones of human natural killer (NK) cells on the proliferation of highly purified normal marrow hematopoietic progenitor cells. Individual NK clones suppressed granulocyte, monocyte, erythroid, or mixed colony formation in a heterogeneous but clonally stable manner. Inhibition of colony growth required a period of close cell contact between NK cell and progenitor cell with maximum inhibition occurring after 8 to 18 hours of preincubation time. The mechanism of killing was at least partially humoral, however, as cell-free supernatants generated by NK clones "activated" by contact with a target cell also inhibited progenitor cell growth. One of the possible humoral mediators was identified as gamma-interferon by studies with specific neutralizing monoclonal antibodies. These results show that clonal NK lines can be further activated by coming in contact with hematopoietic progenitor cells, resulting in substantial inhibition of colony formation in vitro. PMID- 3098322 TI - Human acute unclassified leukemia with a unique t(4;17) chromosomal translocation expresses T lymphoid and myeloid surface antigens after in vitro culture. AB - Bilineage differentiation along both the T lymphoid and the myeloid lineage while in in vivo diffusion chamber (DC) and in vitro suspension culture was observed in a case of acute unclassified leukemia (null-AL) and t(4;17). Prior to culture, the blast cells were TdT and la positive but did not express any lineage-specific antigenic markers. Furthermore, the immunoglobulin heavy chain and T cell receptor beta-chain genes were in germline configuration. Cytogenetically, all metaphases had the unique translocation t(4;17) (q25;q23) prior to and after culture, supporting the leukemic origin of the cells. During both DC culture and suspension culture with and without tetradecanoyl-phorbol-acetate (TPA), a substantial increase in the absolute and relative number of cells expressing both myeloid and T lymphoid antigenic markers occurred. Double-fluorescence analysis demonstrated the expression of antigenic markers of both lineages on the same population of cells, and electron microscopy revealed the induction of myeloperoxidase after both DC and suspension culture. Immunoglobulin heavy chain and T cell receptor beta-chain genes remained in germline configuration after treatment with TPA, when analyzed with JH and CT beta probes, respectively. These findings indicate that this case represents a null-AL with dual-lineage capabilities, which has probably arisen from the malignant transformation of a bipotential stem cell of lymphoid and myeloid progeny. PMID- 3098324 TI - Amantadine potentiates T lymphocyte killing by an anti-pan-T cell (CD5) ricin A chain immunotoxin. AB - The studies described in this report demonstrate that 1-adamantanamine hydrochloride (amantadine) is a potent enhancer of the cytotoxic activity of the anti-pan-T lymphocyte (CD5) T101 monoclonal antibody conjugated to purified ricin A-chain (T101-immunotoxin; T101-IT). We also demonstrate that T101-IT in the presence of amantadine does not induce immunotoxin-mediated cytotoxicity in nontarget cells such as human marrow hematopoietic progenitor cells. These results provide further knowledge for the improvement of ex vivo purification of human bone marrow from normal or leukemic T cells prior to allogeneic or autologous stem cell transplantation, respectively. Furthermore, since amantadine has long been employed safely in human therapy, its use in conjunction with immunotoxins might be exploited in vivo. PMID- 3098323 TI - Erythroid marrow function in anemic patients. AB - Erythropoietic activity is known to be closely associated with marrow iron uptake. A modification of the standard measure of plasma iron turnover has been developed in which erythron transferrin uptake (ETU) rather than iron uptake has been calculated. The ETU has the advantage of providing a parameter of erythroid marrow activity independent of change produced by plasma iron and transferrin saturation. Measurements in 80 patients with anemia were compared to the normal value of 60 +/- 12 mumol/L whole blood/d. The mean ETU for ten patients with severe aplastic anemia and for six patients with pure red-cell aplasia were 12 +/ 8 and 12 +/- 11 mumol/L whole blood/d, respectively. In ten transfusion dependent patients with renal failure under dialysis therapy, the mean value was 35 +/- 11, while ten other dialyzed patients who were transfusion independent had a mean ETU of 73 +/- 21 mumol/L whole blood/d. Sixteen patients with hemolytic anemia had an average ETU of 400 +/- 130, while 28 patients with ineffective erythropoiesis had a mean value of 474 +/- 147 mumol/L whole blood/d. While patients with hypoproliferative anemia showed no relation between the severity of anemia and ETU, those with hyperproliferative erythroid marrow showed increasing values as the anemia became more severe. Sequential measurements in patients with aplastic anemia under treatment and in thalassemic patients under transfusion therapy showed the value of this measurement in monitoring the effects of treatment on erythroid marrow activity. It is concluded that the measurement of ETU provides a more direct ferrokinetic evaluation of erythroid activity in anemic states. PMID- 3098325 TI - Marrow purging in autologous bone marrow transplantation for T-lineage acute lymphoblastic leukemia: efficacy of ex vivo treatment with immunotoxins and 4 hydroperoxycyclophosphamide against fresh leukemic marrow progenitor cells. AB - A lymphoblast progenitor cell assay was used to evaluate the antileukemic efficacy of marrow-purging protocols that employed intact ricin immunotoxins (IT) and 4-hydroperoxycyclophosphamide (4-HC) against clonogenic primary T-lineage marrow blasts freshly obtained from 12 T-lineage acute lymphoblastic leukemia (ALL) patients. Residual T-lineage blast colonies were observed after treatment with 1 micrograms/mL T101 (anti-CD5)-Ricin (R) + G3.7 (anti-CD7)-R in eight of 12 cases and after 100 micrograms/mL 4-HC in six of nine cases. By comparison, a combination of IT and 4-HC proved very effective against T-lineage leukemic progenitor cells, and no residual blast colonies were observed in any of the eight cases studied. We conclude that future trials should consider combined treatment protocols such as IT + 4-HC for more effective purging of autologous marrow grafts. PMID- 3098327 TI - Induction of NK activity in large granular lymphocyte leukemia: activation with anti-CD3 monoclonal antibody and interleukin 2. AB - Large granular lymphocyte (LGL) leukemia is a rare disease characterized by clonal expansion of LGL associated with chronic neutropenia, multiple auto antibodies, and occasionally polyarthritis. We studied cell surface antigen expression and functional activity of leukemic LGL from ten such patients. Using two-color flow cytometric analysis, we found that leukemic LGL from all ten patients expressed the CD3 and HNK-1 markers, while cells from only four patients expressed IgG Fc receptors (FcR). The LGL leukemic cells had little or no NK activity (defined as MHC-nonrestricted cytotoxicity against K562 target cells); however, NK activity could be induced in leukemic LGL by in vitro treatment with as little as 0.05 microgram/mL of anti-CD3 monoclonal antibody. Cell sorting experiments demonstrated that NK activity was induced in CD3+ leukemic LGL (either CD3+, HNK-1+ or CD3+, FcR+) with anti-CD3 monoclonal antibody but not in normal CD3+, FcR- T cells. Treatment with purified interleukin 2 (IL 2) also caused direct activation of some CD3+ leukemic LGL. Despite induction with anti CD3 MAb or IL 2, activated leukemic LGL did not proliferate or express high density IL 2 receptors detectable by cell sorter analysis. Treatment with alpha interferon had minimal effect on NK activity of LGL leukemic cells. These results suggest that leukemic LGL may provide a useful model for examining the signals required for LGL maturation and activation. PMID- 3098326 TI - Platelet aggregation in whole blood from patients with Glanzmann's thrombasthenia. AB - We examined platelet aggregation in platelet-rich plasma (PRP) and in whole blood from two patients with Glanzmann's thrombasthenia. In PRP, aggregation was measured by monitoring the changes in light absorbance that occurred in response to aggregating agents; to measure platelet aggregation in whole blood, we used a platelet counting technique. In PRP, the patients' platelets showed defective aggregation in response to ADP, adrenaline, arachidonic acid (AA), and collagen, but normal agglutination occurred in response to ristocetin. In whole blood, however, platelet aggregation in response to the aggregating agents appeared to be either very similar to that which occurred in blood from normal subjects or only slightly reduced. There was a reduced response to all concentrations of ADP and to low concentrations of collagen but a normal response to all concentrations of adrenaline, AA, and higher concentrations of collagen. Conversely, there seemed to be an increased agglutination response to ristocetin. The abnormality in our two patients with Glanzmann's thrombasthenia probably lies in the inability of their platelets to form large, macroscopic aggregates rather than in platelet aggregation per se. PMID- 3098328 TI - Immunoglobulin and T cell receptor gene rearrangements in human lymphoma and leukemia. AB - DNA samples from blood leukocytes or tumor biopsies of 45 patients with phenotypic B or T cell neoplasms were analyzed for rearrangements of the immunoglobulin (Ig) or T cell receptor (TCR) genes by Southern blot hybridization analysis. Rearrangements of the Ig heavy chain joining region genes (JH) were present in DNA from each of 28 B cell lymphomas and leukemias; 14 of 21 of these tumors also had rearrangements of the Ig kappa light chain joining (JK) or deleting element (KDel) genes. Conversely, 16 of 17 T cell lymphomas and leukemias had rearranged TCR beta chain genes. One B cell and one T cell tumor had rearrangements of both Ig and TCR genes. There was a strong correlation between the rearrangements of specific genes and the immunophenotype of the tumor: JH rearrangement without TCR beta chain rearrangement occurred only in B cell tumors; TCR beta chain rearrangement with or without JH rearrangement occurred only in T cell tumors, with one exception; and JK and KDel rearrangements were found only in B cell tumors. Thus, rearrangements of the Ig heavy and light chain genes and the TCR beta chain genes were found to be highly sensitive markers of monoclonal human lymphomas and lymphoid leukemias, with the type of gene rearrangements well correlated with the cell lineage of these neoplasms. PMID- 3098329 TI - Evidence favoring lineage fidelity in acute nonlymphocytic leukemia: absence of immunoglobulin gene rearrangements in FAB types M4 and M5. AB - The concept of lineage fidelity in acute leukemia has recently been challenged by the finding of rearrangements of the immunoglobulin heavy chain genes in a leukemic cell line and in a small number of sporadic cases of acute nonlymphocytic leukemia with a monocytic phenotype. We therefore screened leukemic blood or bone marrow samples of 33 adult patients with acute nonlymphocytic leukemia of FAB types M4 (23 patients) and M5 (10 patients); 28 were obtained at diagnosis and 5 at relapse. All cases were well characterized pathologically and histochemically. Cytogenetic analysis performed in each case demonstrated karyotypes that were representative of those generally seen in these types of leukemia, with a clonal abnormality present in all except 9 of 32 patients who were successfully studied. DNA prepared from each sample was digested with the restriction enzyme BamH1 and analyzed by Southern blot hybridization to probes for the JH region of the immunoglobulin heavy chain. All 33 cases had DNA retained in the germline configuration with no evidence of rearrangement. This finding supports the concept of lineage fidelity, and suggests that true interlineage infidelity, myeloid to lymphoid, is a rare occurrence in adult acute nonlymphocytic leukemia. PMID- 3098330 TI - Polychlorinated biphenyl residues in some marine organisms from the Baie des Anglais (Baie-Comeau, Quebec, Saint-Lawrence estuary). PMID- 3098331 TI - Purification of PCB contaminated water by chitosan: a biological test of efficiency using the common barbel, Barbus barbus. PMID- 3098333 TI - Making NMR cost-effective. PMID- 3098332 TI - [Cryptophthalmia. Discussion of a familial case]. PMID- 3098335 TI - Panic attacks. PMID- 3098334 TI - Comparison of the nutritional state of new and long-term patients in a psychogeriatric unit. AB - Nutritional deficiencies have been implicated in the pathophysiology of various mental disorders. Life in institutions has been associated with development of nutritional deficiencies, the elderly being most at risk especially those with senile dementia. In this study nutritional status, particularly vitamin and essential mineral status was assessed in a group of 64 new admissions to a psychogeriatric unit and 49 long-term patients. The results indicated that psychogeriatric patients were at risk of experiencing nutritional deficiencies and those with senile dementia were likely to have more abnormalities than those with functional illnesses. Those patients in long-term care would appear to have a better nutritional state than those on admission. PMID- 3098336 TI - Supplementary feeds following femoral neck fracture. PMID- 3098337 TI - The health of travellers. PMID- 3098338 TI - Markers for insulin dependent diabetes: towards early detection. PMID- 3098340 TI - Effects of breast conservation on psychological morbidity associated with diagnosis and treatment of early breast cancer. AB - Psychiatric morbidity was assessed in 101 women treated for early breast cancer (T0,1,2,N0,1,M0). Patients had expressed no strong preference for treatment, so were randomised to either mastectomy or breast conservation. The incidence of anxiety states or depressive illness, or both, among women who underwent mastectomy was high (33%) and comparable with that found in other studies. Slightly more of the patients who underwent a lumpectomy followed by radiotherapy had affective disorders, 38% having an anxiety state, depressive illness, or both. These findings question the view that mutilating treatment is predominantly responsible for the measurable psychiatric morbidity reported previously. Counselling services should be provided for all women treated for breast cancer, not just those who undergo mastectomy. PMID- 3098339 TI - Increased concentration of circulating calcitonin gene related peptide during normal human pregnancy. AB - Calcitonin gene related peptide is an extremely potent vasoactive peptide that causes profound vasodilatation in man. Its distribution in perivascular nerves suggests that one of its functions may be the regulation of peripheral vascular tone. Pregnancy is a physiological condition in which there are major haemodynamic changes. An increase in plasma volume of about 40% necessitates changes in peripheral vascular tone. In a cross sectional study plasma concentrations of immunoreactive calcitonin gene related peptide were measured throughout normal pregnancy and at five to seven days post partum. Calcitonin gene related peptide concentrations were significantly increased throughout pregnancy but fell after delivery. Calcitonin gene related peptide may participate in the physiological regulation of vasomotor tone in man. PMID- 3098341 TI - Dose dependent response of symptoms, pituitary, and bone to transdermal oestrogen in postmenopausal women. AB - The effect of the plasma oestradiol concentration on climacteric symptoms, gonadotrophin release, and bone resorption was studied in three groups of postmenopausal women given 0.025 mg, 0.05 mg, or 0.1 mg transdermal oestradiol daily. There was a dose related reduction in symptoms, plasma follicle stimulating hormone concentration, and urinary calcium and hydroxyproline excretion. The relation of the response to plasma oestradiol values was similar for each variable with an initial large reduction and little change in response to increases in the plasma oestradiol concentration above 150 pmol/l (41 pg/ml). Hormone replacement therapy producing an effect equivalent to higher oestradiol concentrations is likely to increase the risk of side effects without conferring any additional benefit. PMID- 3098342 TI - Asthma mortality: comparison between New Zealand and England. AB - Causes for the high mortality from asthma in New Zealand were investigated by comparing deaths from asthma in caucasian subjects aged 15-64 in New Zealand with those from asthma in the same age group in two regions in England. There were no significant differences in the accuracy of death certification. The verified asthma mortality in New Zealand (4.2/100,000) was over twice that in England. Many characteristics of patients and management, including poor compliance with treatment and deficiencies in long term and emergency care, were qualitatively similar in the two countries. New Zealand had an apparently higher rate of non preventable deaths from asthma, suggesting a greater severity of asthma in New Zealand. In both countries, however, most deaths were associated with poor assessment, underestimation of severity and inappropriate treatment (over reliance on bronchodilators and underuse of systemic corticosteroids), and delays in obtaining help. A greater frequency of some of these deficiencies in management remains a possible additional explanation for part of the excess mortality in New Zealand. PMID- 3098343 TI - Finger clubbing in the Zollinger-Ellison syndrome. PMID- 3098344 TI - Neuropsychiatric complications related to use of prazosin in patients with renal failure. PMID- 3098345 TI - Epidural methadone for preoperative analgesia in patients with proximal femoral fractures. PMID- 3098346 TI - Thirty one years of herpes zoster in a rural practice. AB - The principal finding in this study of 151 cases of herpes zoster in a rural practice was the predominance of patients who had a lesion on the right side. This supports the proposition that the site of occurrence may be determined by repeated trauma. The decline in the frequency of attacks in older men was significant. Studying these cases and published reports has elucidated some of the problems of the occurrence and distribution of herpes zoster in the body, which still await definition. Others may be encouraged to carry these studies further. PMID- 3098347 TI - What is a good GP? PMID- 3098348 TI - Vaginal discharge. PMID- 3098350 TI - Time to scrap creatinine clearance? PMID- 3098349 TI - Efficacy of phototherapy in non-haemolytic hyperbilirubinaemia. AB - Clinical experience of phototherapy for non-haemolytic hyperbilirubinaemia in 3999 infants in Kandang Kerbau Hospital, Singapore, is documented. Phototherapy was most effective in extremely preterm infants with very low birth weight (gestation less than or equal to 32 weeks, birth weight less than or equal to 1500 g) and least effective in full term infants with very low birth weight (gestation greater than or equal to 37 weeks, birth weight less than or equal to 1500 g) and large preterm infants (gestation less than 37 weeks, birth weight greater than 2270 g). Overall, phototherapy was effective in almost all the infants, with a failure rate of only 2.00/1000 infants. No characteristic features common to all the failures could be detected. The bilirubin rebound was usually mild; repeat phototherapy was required in only 30 infants (7.50/1000), with the response to the second exposure comparable to that to the first. No infant required a third exposure. All the infants tolerated phototherapy well, none developing any illness that could be attributed to the treatment. This clinical experience shows that phototherapy for the treatment of nonhaemolytic hyperbilirubinaemia is effective and safe. PMID- 3098351 TI - Neurological and neurosurgical approaches in the management of malignant brain tumours. PMID- 3098352 TI - Why women are not receiving anti-Rh prophylaxis. PMID- 3098353 TI - One man's burden. PMID- 3098354 TI - Enhanced survival of rat neonatal cerebral cortical neurons at subatmospheric oxygen tensions in vitro. AB - In vitro tissue culture experiments are routinely performed at atmospheric oxygen tension (21%), although most cells experience lower oxygen tensions in vivo. The optimal oxygen tension for the survival of neurons and synthesis of neurofilament (NF) was determined using dissociated neonatal rat cerebral cortex and monoclonal antibodies to the 68 kDa and 200 kDa subunits of NF. Maximum production of each subunit determined by Enzyme-Linked Immunosorbant Assay occurred at 9% O2. Neuronal survival determined by immunohistochemistry was also maximal at 9% O2. CNS neurons are highly sensitive to oxygen tension and grow best at levels approximating capillary rather than atmospheric pO2. PMID- 3098355 TI - Calcium and protein kinase C inhibit biosynthesis of Aplysia egg-laying hormone. AB - Previous studies on the biosynthesis of the peptide egg-laying hormone (ELH) of Aplysia have suggested that the increase in cAMP levels associated with the initiation of a bag cell discharge stimulated ELH synthesis, whereas the calcium influx associated with the discharge inhibits it. This report provides additional documentation of the inhibitory role of calcium. Inhibition by the calcium ionophore A23187 was shown to be dependent on the presence of extracellular calcium. A23187 inhibited ELH synthesis and exposure to 0 Ca2+/2 mM EGTA medium stimulated it in bag cell somata surgically deprived of their sites of synaptic input. The tumor-promoting phorbol ester, TPA, inhibited ELH biosynthesis in a calcium-dependent fashion, whereas the non-tumor-promoting 4 alpha-phorbol did not. These results are consistent with the hypothesis that calcium entry during bag cell discharge may inhibit ELH synthesis via activation of protein kinase C, thus counteracting the stimulation by cAMP early in the discharge. Such a mechanism could precisely regulate the production of ELH molecules to replace those lost by secretion. PMID- 3098356 TI - A treatment program for failure to thrive: a cost/effectiveness analysis. AB - Failure to thrive (FTT) is a frequent cause for the admission of infants to the hospital. Such hospitalizations are often lengthy and expensive, and usually do not contribute to an understanding of the etiology of FTT. Generally, organic causes of FTT can be ruled out by a thorough history and physical examination. In this study two groups were examined: 17 infants who were admitted to foster medical placement homes (MPH), private homes with specially trained parents; and a comparison group of 18 infants who were treated in a more traditional way with diagnostic hospitalization. The groups were similar in all regards prior to admission. All infants were less than a year of age. Family disruption was a prominent feature in both groups, but socio-demographic analysis showed them to be similar in all areas studied. The comparison group gained an average of 276 grams in the hospital over 8.6 days. The MPH group gained 362 grams in the hospital over 8.7 days, with an additional 1270 grams in the medical placement home over 31.1 days. Five children were admitted to the medical placement home without hospitalization. After correcting for an expected weight gain of 15 grams per day (normal growth), the comparison group showed a catch-up growth of 16 gms/day, while the MPH group gained 29 gms/day in excess of expectation, almost twice the comparison group. A 100-gram weight gain cost +308 in the MPH program and +1,635 in the traditional approach. This five-fold difference was felt to be a significant deterrent to the continuing approach of admitting children to the hospital for for the workup of FTT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098357 TI - [Determination of kinetic constants in the general case of cooperative type or Michaelis enzymes inhibited by their substrate: theoretic analysis]. AB - For an enzyme (E) susceptible to substrate (S) inhibition, (S) can bind on one hand to (E) and on the other hand to (ES), leading to the dead-end complexes (SE) and (SES). In the general case where the (E)/(S) interaction obeys the Hill equation, the theoretical maximum velocity VM can be estimated when n not equal to 1, from the determination of velocities v beta at substrate concentrations S beta = Sm beta where Sm is the value corresponding to the actual maximum velocity vm. The Hill coefficient (n) as well as the constants KS, KSE and KSES corresponding to the respective dissociations of the complexes (ES), (SE) and (SES) are then determined from the equation: Ln (v/(VM-v] = nLnS-LnKS(1 + Sn/KSE + S2n/KS KSES) and its two asymptotes. PMID- 3098358 TI - [Casein-like immunoreactivity in the male rat]. AB - A substance presenting a beta-casein-like immunoreactivity (beta-cas-LI) was found in male serum and tissues. This beta-cas-LI was measured by a specific radioimmunoassay using a purified beta-casein and an anti beta-casein kindly supplied by L. M. Houdebine. Serial dilutions of serum or tissues samples showed a good parallelism to the standard curve. In male rat, beta-cas-Li was found in all sera and in some tissues = mammary gland, prostate and testis which contained respectively 6,200, 408 and 38 ng per organ. beta-cas-LI value in the serum was regulatable. Hypophysectomy and long-term castration strongly reduced basal levels. Insertion of testosterone silastic capsules (25 mg/capsule) was able to restore control values, while estradiol (E2) (4 mg/kg E2 valerianate) to castrated or intact rats increased serum beta-cas-LI above basal values. In conclusion, these results showed, for the first time, the presence in male rat serum and tissues of a beta-casein immunoreactive-like substance. Moreover, this beta-cas-LI seemed to be under pituitary and gonad regulation. PMID- 3098359 TI - [Clinical use of echocardiographic Doppler color flow mapping]. PMID- 3098360 TI - [Diagnosis of left-to-right shunts in congenital heart diseases by echocardiographic Doppler color flow mapping]. PMID- 3098361 TI - [Relation between serum lipid levels and nutrient intake in healthy urban and rural inhabitants of Shanghai]. PMID- 3098363 TI - [Is hypercholesterolemia related to serum zinc and copper concentrations?]. PMID- 3098362 TI - [Permeability changes in the myocardial cell membrane in dilated cardiomyopathy. Observations with electron tracers]. PMID- 3098364 TI - [Chromosome aberration rates and heritable susceptibility to esophageal cancer]. PMID- 3098365 TI - [Pisum sativum lectin receptor in normal epithelial and squamous cancer cells of the human esophagus]. PMID- 3098366 TI - [Linkage between HLA and the susceptibility gene of psoriasis]. PMID- 3098367 TI - [Differentiation of radiation injuries in postradiation recurrence of nasopharyngeal cancer]. PMID- 3098369 TI - [Changes in renal volume and function in the aged]. PMID- 3098368 TI - [Effect of testosterone propionate on jejunal and ileal zinc absorption in rats]. PMID- 3098370 TI - [Auditory brain stem response of people in their senium and presenium]. PMID- 3098371 TI - [Hypocholesterolemia and cancer]. PMID- 3098372 TI - [Intrahepatic viral DNA in 98 patients with viral hepatitis B]. PMID- 3098373 TI - [Oral administration of branched-chain amino acids in the treatment of hepatic disease]. PMID- 3098374 TI - [Reference values of serum apolipoprotein A-I and B]. PMID- 3098375 TI - [Preventive effect of rubber-seed oil on atherosclerosis in the rhesus monkey]. PMID- 3098376 TI - [Role of lidocaine in protecting central neurons from ischemic or anoxic damage]. PMID- 3098377 TI - [Synthesis of human proinsulin and its clinical significance]. PMID- 3098378 TI - [Social inequalities in the health field]. PMID- 3098379 TI - [The role of health expenditures by head of household: long-term view and current developments]. PMID- 3098381 TI - Health care financing's federal heritage. PMID- 3098380 TI - The Davis nursing model for long term care. PMID- 3098382 TI - Nursing models for long term care. PMID- 3098383 TI - The tension between work and growth: a cellular concern. PMID- 3098384 TI - Longitudinal study of bone loss in the second metacarpal. AB - This longitudinal study was undertaken to ascertain the rate of bone loss and to identify aging, cohort and/or time effects on bone loss in male participants of the Baltimore Longitudinal Study of Aging. Hand-wrist radiographs were obtained from 1958-1981 and were evaluated for total width, medullary width, and length of the second metacarpal. Data were analyzed using an age-time matrix with 8-year intervals for three epochs and nine age groups. The bone measurements were analyzed in three perspectives (cross-sectional, longitudinal and time-series). The results demonstrate that there is both a cross-sectional and longitudinal loss of cortical bone with age in the second metacarpal. Furthermore, the results show that males lose approximately 14% of their cortical bone, at a rate of about 2% per decade, over the adult lifespan. The majority of this loss occurs between the ages of 45 and 69 and is due primarily to aging and is not an artifact of cohort differences or secular change. PMID- 3098385 TI - Serum bone gla protein (BGP) and other markers of bone mineral metabolism in postmenopausal osteoporosis. AB - Bone gla protein, the vitamin K-dependent protein synthesized by osteoblasts and measured in blood by radioimmunoassay, has been used as an index of the rate of bone turnover. The relationship of bone gla protein with other markers of bone mineral metabolism was determined in 31 untreated postmenopausal women with the osteoporotic syndrome. In addition to serum osteocalcin (BGP) we measured parathyroid hormone (PTH) (carboxyl and mid-molecule fragments), 25(OH)D, alkaline phosphatase, estradiol (E2), estrone (E1), dietary calcium intake, 24 hour urinary calcium excretion, and bone mineral density by CT scan of the lumbar vertebrae. Significant osteopenia was present on CT in untreated postmenopausal osteoporotic women (bone density in 18 out of 31 was below the critical value of 60 mg/cm3). Serum BGP correlated positively with CT scan (r + 0.647, P less than 0.001). CT and age were negatively correlated (r - 0.661, P less than 0.001) while CT and E2 showed a positive correlation (r + 0.554, P less than 0.01). Unexpectedly, BGP and age revealed a significant negative correlation (r - 0.421, P less than 0.05). These findings suggest a state of low bone turnover in this group with untreated postmenopausal osteoporosis. PMID- 3098386 TI - Metabolism of osteocalcin. AB - After intravenous injection, labeled bovine osteocalcin was rapidly removed from rat plasma and taken up mainly by kidney, liver, and bone. The rate of disappearance was slowed by nephrectomy but not as much by ureteric ligation, suggesting renal destruction of osteocalcin rather than renal excretion. Both liver and kidney tissue rapidly degraded osteocalcin, both in vivo and in vitro. The enzyme activity was found in microsomal, mitochondrial, and supernatant fractions. EDTA was the most potent inhibitor, suggesting that metalloenzymes are involved. Comparison of three methods of analysis--trichloroacetic acid precipitation, gel filtration on Sephadex G-50, and SDS polyacrylamide gel electrophoresis--showed that the last gave a much faster rate of degradation of osteocalcin and suggests that osteocalcin and/or fragments bind to larger proteins in the tissue homogenates. PMID- 3098387 TI - Chemotaxis of muscle-derived mesenchymal cells to bone-inductive proteins of rat. AB - In this investigation we examined the chemotaxis of muscle-derived mesenchymal cells from neonatal rats to partially purified extracts of demineralized bone matrix with osteoinductive properties. Using the modified Boyden chamber assay and muscle-derived mesenchymal cells obtained from neonatal Long-Evans rats, we tested the chemotactic properties of the 4 M guanidine-HCl extract from demineralized rat bone matrix and fractions thereof that were derived from sequential Sepharose CL-6B, TSK-3000 and HPLC-C18 chromatography. We have identified that those fractions exhibiting chemotactic properties were also osteoinductive. Therefore, demineralized bone matrix serves as its own soluble signal and insoluble substratum in the inductive process leading to endochondral bone formation in vivo. PMID- 3098388 TI - The origin of osteoclasts: an immunohistochemical study on macrophages and osteoclasts in embryonic rat bone. AB - The origin of osteoclasts was studied in embryonic rat bone primordia using a set of monoclonal antibodies (ED1, ED2, and ED3) that exclusively recognize monocytes and macrophage. ED1 recognizes monocytes and macrophages. Mononuclear phagocytes which were ED1 positive were found in the perichondrium/periosteum of developing bone. These cells started to infiltrate the primordia when the cartilage became hypertrophic. During bone formation, multinucleated ED1-positive cells with the morphological characteristics of osteoclasts were found in the developing bone marrow cavity and against the bone collar. The present findings support the notion that osteoclasts arise by fusion of mononuclear phagocytes derived from blood monocytes. PMID- 3098389 TI - Osteoporosis and mandibular bone resorption in the Sprague Dawley rat. AB - Mandibular bone resorption in normal and osteoporotic rats was measured using standard scintillation techniques for tritiated tetracycline (H3-TC). Thirty-four Sprague-Dawley rats were labeled with H3-TC at 4-9 weeks of age. Ten animals were then sacrificed for baseline radioactivity levels, while 12 experimental animals were given a high protein, low calcium diet, and 12 control animals were given a normal calcium diet. Osteoporotic and normal diets were instituted for 90 days. The results show a significant reduction in the quantity of bone in the experimental group (P less than .05) as compared to the control group. In addition, serum samples collected were found to contain significantly elevated (P less than .01) alkaline phosphatase level in the experimental group when compared to the control group. PMID- 3098390 TI - A new culture method assuring the three-dimensional development of the mouse embryonic molar tooth in vitro. AB - Mandibular first molars from 17-day-old mouse embryos were cultivated in vitro for 10 days using a new organ culture method. This method consisted of using a small glass dish and an agar chamber to slowly float the molars to the gas-medium interface where they were maintained by the surface tension of the medium. The molars developed three-dimensionally through the use of this method. Five cusps with refractile dental matrix were recognized from the occlusal side. It was easy to determine antero-posterior and bucco-lingual orientation of the molars. Thick sections of the bucco-lingual plane showed the normal cytodifferentiation of ameloblasts and odontoblasts. The thick enamel layer was formed to the extent of the fissure region between cusps. Furthermore, a great quantity of stippled material accumulated between the enamel and the ameloblasts. The stippled material displayed a meshlike fibrilar structure, and at the mineralization front, it seemed that the fibrils of stippled material adjacent to the enamel had been transformed into needlelike enamel crystals. In addition, bundles of the fibrils similar to enamel crystals were found in the stippled material. As the floatation method resulted in the three-dimensional development of the molars and the development of the enamel without the presence of histological disturbances, it was considered superior to other culture methods for the facilitation of orientation and the development of cusps. PMID- 3098391 TI - Calcium homeostasis. III: The bone membrane potential and mineral dissolution. AB - Active ionic transport through the bone membrane appears to be involved in the regulation of calcium level in the bloodstream. This transport process can be monitored by the transmembrane electrical potential difference, which increases in the presence of parathyroid hormone. The present work is an evaluation of the constraints placed on the system by the solubility limit of the mineral phase. A thermodynamic analysis demonstrates that control of mineral dissolution can only occur when the transported species is one of the mineral phase constituents. A combination of previous experimental results with the present development limits the possible active transport mechanism responsible for the adjustment of mineral dissolution/deposition to: an outward-directed pump for hydroxyl ion, an outward directed pump for phosphate ion, or an inward-directed pump for hydrogen ion. PMID- 3098392 TI - Equatorial diffraction spacing as a function of water content in fully mineralized cow bone determined by neutron diffraction. AB - Variation of the equatorial diffraction spacing of soft type I collagen tissues with water content using X-rays has been known for many years. Recently, a generalized model for collagen molecule packing within fibrils was deduced from this information for different collagenous tissues. It is now known that the eq. diff. sp. of mineralized tissues can be less than for soft tissues and is inversely dependent on the wet density. A determination of the eq. dif. sp. dependence on water content using neutron diffraction of fully mineralized cow bone was undertaken for comparison. Specimens with various partial water content between 0 and 100% were tested. Data show collagen molecules pack more closely together as water content decreases, just as for soft tissues. PMID- 3098394 TI - Myocardial oxygen supply during hypocapnia and hypercapnia in the dog. AB - It has been postulated that a coronary vasoconstriction during hypocapnia might be opposed by a compensating coronary vasodilatation due to impaired myocardial oxygen supply. The present study was performed first to examine whether a maximal decline in coronary sinus (CS) oxygen content was reached during hypocapnia. During hypercapnia a myocardial "over perfusion" has been demonstrated. The second purpose of the present study was to examine whether a myocardial "over perfusion" is essential to maintain a sufficient myocardial tissue oxygen supply during hypercapnia. Closed-chest dogs were anesthetized with pentobarbital and hypocapnia was induced by hyperventilation. Nitrogen gas and carbon dioxide could both be added to the inspiratory gas to create arterial hypoxemia (arterial SO2 65%) and hypercapnia, respectively. Arterial hypoxemia during hypocapnia increased myocardial blood flow (MBF) by 50%, while CS SO2 decreased significantly. The decrease in CS SO2 demonstrates a reserve capacity of myocardial oxygen extraction during hypocapnia, thereby ruling out any major coronary vasoconstriction during hypocapnia. Hypercapnia during normoxemia increased MBF, myocardial oxygen delivery, and CS SO2 substantially, but this was not observed when hypercapnia was created during arterial hypoxemia. From the present results we conclude that hypocapnia does not cause any major coronary vasoconstriction, while hypercapnia results in a myocardial "over perfusion," which is a luxury perfusion not essential to maintain sufficient myocardial oxygen supply during hypercapnia. PMID- 3098393 TI - Pharmacological characterization of airway smooth muscle responses to antigen in ascaris-sensitive dogs. AB - The dog model of ascaris airway sensitivity was chosen because of its frequency and its immunologic similarity to the human atopic asthmatic state. We studied the mediators of the antigen-induced airway response in vitro and the alterations in the in vivo and in vitro responsiveness to spasmogens evoked by antigen challenge. A myogenic basis of altered reactivity was suggested by the following: tetrodotoxin-insensitive spontaneous active tone; phasic contractions of airway smooth muscle; and responsiveness to leukotrienes C4 and D4. The pharmacologic characteristics of the antigen-induced airway smooth muscle contraction in vitro were similar to those induced by arachidonic acid and the leukotrienes only in some respects but were clearly different from those induced by compound 48/80. This suggested a predominant role for arachidonate lipoxygenase products. Histamine appeared to play a minor role in the antigen response. Comparisons were made between antigen-induced responses of actively and passively sensitized airways tissues. In the latter, histamine release appeared to contribute to the initial antigen-induced contraction and, unlike in actively sensitized airways, the responses were easily desensitized to repeated challenge. Alterations of airway responsiveness were demonstrated in vivo to acetylcholine and 5-HT following antigen challenge of highly ascaris-sensitive dogs. In vitro studies of passively sensitized muscle showed selectively enhanced response to 5-HT following antigen challenge. These studies support the presence of altered myogenic properties of airway smooth muscle and nonspecific increased airway responsiveness in this animal model. PMID- 3098395 TI - Maintenance of tone, role of arachidonate metabolites, and effects of sensitization in guinea pig trachea. AB - A study was made of the mechanisms underlying production of resting active tension in guinea pig tracheal smooth muscle and the changes with active sensitization to ovalbumin. The same types of tissues were also analyzed as to their responses to arachidonate. Responses for each tissue were expressed in relation to a scale between zero active tension and maximum active tension in response to carbachol. A variety of selective and nonselective inhibitors of cyclooxygenase or 5-lipoxygenase were shown to affect active tension in a manner consistent with the conclusion that a cyclooxygenase product, probably prostaglandin F(PGF2 alpha) and not thromboxanes was chiefly responsible. The inhibition of active tension produced by cyclooxygenase inhibition was shown to be related to the initial active tension, such that tissues with greater resting active tension had greater reductions in tone. No differences of major importance were found as to the mechanisms underlying tone production in control and sensitized tissues. The tension changes in response to exogenous arachidonate were also found to be dependent on the initial level of active tension; when this was low, tension increased, when it was high, tension decreased or did not change. Effects of inhibitors on these responses were again consistent with the conclusion that primarily excitant prostaglandins, not thromboxanes, were produced. Some suggestive evidence for production of excitatory and inhibitory nonprostaglandin metabolites was obtained. No difference of major importance between control and sensitized tissues was observed in the magnitude or underlying mechanism of production of active tension. PMID- 3098396 TI - Characterization and partial purification of a broad spectrum antibiotic AS-48 produced by Streptococcus faecalis. AB - Streptococcus faecalis S-48 produces a broad spectrum antibiotic, active against Gram-positive and Gram-negative bacteria. This substance is produced in solid and liquid media and also in a defined basal medium. It is sensitive to protease, pronase, or trypsin, heating at 70 degrees C, and alkaline pH, but resistant to treatment with lipase, lysozyme, alkaline phosphatase, DNAase, RNAase, acidic or neutral pHs, and also lower temperatures (60 degrees C). Several organic solvents cause precipitation, but not inactivation. This antibiotic has been partially purified by gel filtration and further ion-exchange chromatography. Its molecular weight has been estimated close to 2000. The biological activity of this antagonistic substance against the selected indicator strains, Streptococcus faecalis S-47 and Escherichia coli U-9, is bactericidal. The characterization of this substance, initially classified as a bacteriocin, indicates that it is an antibiotic of peptidic nature. The significance of antibiotic occurrence in group D of the genus Streptococcus is also discussed. PMID- 3098397 TI - Growth and thermal inactivation of Listeria monocytogenes in cabbage and cabbage juice. AB - Studies were done to determine the interacting effects of pH, NaCl, temperature, and time on growth, survival, and death of two strains of Listeria monocytogenes. Viable population of the organism steadily declined in heat-sterilized cabbage stored at 5 degrees C for 42 days. In contrast, the organism grew on raw cabbage during the first 25 days of a 64-day storage period at 5 degrees C. Growth was observed in heat-sterilized unclarified cabbage juice containing less than or equal to 5% NaCl and tryptic phosphate broth containing less than or equal to 10% NaCl. Rates of thermal inactivation increased as pH of clarified cabbage juice heating medium was decreased from 5.6 to 4.0. At 58 degrees C (pH 5.6), 4 X 10(6) cells/mL were reduced to undetectable levels within 10 min. Thermal inactivation rates in clarified cabbage juice (pH 5.6) were not significantly influenced by the presence of up to 2% NaCl; however, heat-stressed cells had increased sensitivity to NaCl in tryptic soy agar recovery medium. Cold enrichment of heat stressed cells at 5 degrees C for 21 days enhanced resuscitation. Results indicate that L. monocytogenes can proliferate on refrigerated (5 degrees C) raw cabbage which, in turn, may represent a hazard to health of the consumer. Heat pasteurization treatments normally given to cabbage juice or sauerkraut would be expected to kill any L. monocytogenes cells which may be present. PMID- 3098398 TI - Melanogenesis in murine B16 cells exposed to Aeromonas hydrophila cytotoxic enterotoxin. AB - Specific markers (growth, melanogenesis) of B16 murine melanoma cells in culture were used as indicators of toxin production by Aeromonas hydrophila. Cytotonic enterotoxinlike activity (inhibited growth, raised tyrosinase activity, and melanin accumulation) occurred at cytotoxic end points of purified beta-hemolysin and several culture filtrates. Antihemolysin rabbit serum inhibited this activity. A hemolysin-neutralized culture filtrate concentrate (10X) failed to elevate tyrosinase relative to untreated and cholera toxin treated controls. Similar dilution profiles using Chinese hamster ovary cells showed limited cell extension only at cytotoxic end points with antihemolysin inhibiting this activity. Cytotoxicity of Chinese hamster ovary cells and B16 cells was proportional to hemolytic activity, with B16 cells showing about 100-fold greater sensitivity on a per cell basis. Cell culture cytotoxicity attributed to beta hemolysin correlated with reactivity in rabbit ileal loop assays. The ADP-ribosyl transferase activity of concentrated (10X) A. hydrophila culture filtrates and fractions thereof was negative. Apparently sublethal doses of A. hydrophila beta hemolysin can nonspecifically stimulate cyclic adenosine monophosphate mediated events in melanoma and Chinese hamster ovary cell assays, producing lower activities than cholera toxin with shorter lag times. PMID- 3098399 TI - Biosynthetic studies on N-acetylmannosaminuronic acid containing teichuronic acid in Bacillus megaterium. AB - The particulate enzymes obtained from four strains of Bacillus megaterium AHU 1240, AHU 1373, AHU 1375, and T catalyzed the synthesis of a polysaccharide and glycolipids from UDP-N-acetylmannosaminuronic acid, UDP-N-acetylglucosamine, and UDP-glucose. Chemical studies involving Smith degradation, acid hydrolysis, and N acetylation revealed that the polysaccharide product has a backbone made up of trisaccharide repeating units comprising glucose, N-acetylmannosaminuronic acid, and N-acetylglucosamine and that the main oligosaccharide moieties of the glycolipids were identical with N-acetylmannosaminuronosyl-N-acetylglucosamine and glucosyl-N-acetylmannosaminuronosyl-N-acetylglucosamine. Incubation of the disaccharide-linked lipid with each particulate enzyme in the presence of UDP glucose produced the trisaccharide-linked lipid and a polysaccharide. It is therefore suggested that in this polysaccharide-synthesizing system the repeating unit is formed on a carrier lipid from appropriate nucleotide derivatives first and the polymerization of the units then occurs to synthesize the backbone while the growing chain remains in pyrophosphate linkage to the carrier lipid presumed to be undecaprenol. PMID- 3098400 TI - Safety and efficacy of long-term treatment with inhaled beclomethasone dipropionate in steroid-dependent asthma. AB - An open long-term trial of inhaled beclomethasone dipropionate was carried out in 32 asthmatic patients chronically dependent on systemic corticosteroids. Our objectives were to study the efficacy and safety of beclomethasone and to determine the proportion of patients in whom systemic steroids could be replaced by the new drug. All subjects had a clear history and physical findings of asthma as well as significant improvement in respiratory function after inhalation of salbutamol. Patients were followed for 4 to 8 years. Compared with a baseline period, patients receiving beclomethasone had reduced symptoms and needed less bronchodilator therapy, but their pulmonary function was unchanged. Bronchial biopsy specimens from seven patients who had been taking beclomethasone for as long as 8 years did not differ histologically from specimens from five asthmatic patients who had never taken the drug. Nine patients were able to stop taking systemic corticosteroids within 9 months, eight required them occasionally, and in eight the requirement was substantially reduced; the requirement did not change appreciably in the remaining seven. Inhaled beclomethasone is a safe and effective drug for chronic administration to asthmatic patients, and in 78% of our subjects the need for systemic steroids was substantially reduced or eliminated. PMID- 3098402 TI - Democratic socialism confronts psychiatry. PMID- 3098401 TI - Factor VIII concentrate for hemophilia: comparison of two heat-treated products. AB - In a controlled trial of heat-treated factor VIII concentrate from Cutter Laboratories and from Connaught Laboratories Limited, 25 patients with hemophilia received Cutter factor VIII and 24 patients with hemophilia received Connaught factor VIII. The mean increase in factor VIII level was similar for the two products (1.88% and 1.98% per unit/kg of body weight respectively [p greater than 0.1], or 89% and 95% respectively of the expected increase [p greater than 0.1]). In-vivo survival (the duration of factor VIII in the circulation) was compared after seven infusions of each product. The mean half-disappearance times were 10.7 and 9.1 hours respectively (p = 0.1), and the mean biologic half-lives were 11.6 and 9.9 hours respectively (p = 0.04); the clinical significance of the latter difference is dubious. Both products could be reconstituted satisfactorily from the dried state. Two subjects experienced relatively minor side effects following infusion of one lot of Cutter factor VIII. Individual responses to both products showed considerable variation. Therefore, when it is critical to attain predetermined levels of factor VIII, such as before and after surgery, factor VIII assays should be performed to check the patient's response. PMID- 3098403 TI - Lithium addition in treatment-resistant depression. PMID- 3098404 TI - Plasma hormones in parous, nulliparous and postmenopausal Japanese women. AB - Mechanisms associated with protection against breast cancer in parous women with an early pregnancy are unknown. Elevated or deficient steroid hormone levels or dysfunctional release of prolactin have been postulated. Since these effects have not been reported in low-risk Japanese women, we have compared the hormone levels in age-weight-risk factor matched premenopausal nulliparous and parous Japanese women with established menstrual regularity. Higher luteal phase plasma levels of estradiol and estrone occurred in parous versus nulliparous women, while plasma prolactin and androgen levels were unaltered. It is suggested that the higher estrogen and lower LH levels, as in short versus long menstrual cycles, results from failure of the opioid GnRH. LH axis to return to pre-pregnancy levels. PMID- 3098405 TI - Phosphoproteins recognized by an H-2-linked immune response gene and their association with cell proliferation. AB - An H-2-associated immune response gene which maps to the I-A subregion of the H-2 complex governs the ability of H-2 congenic mice to mount an antibody response to five phosphoproteins with molecular weights of 33,000, 29,000, 23,000, 17,000, and 16,000 when inoculated with BW5147, a spontaneous AKR T-cell leukemic cell line. The phosphoproteins are present in all tumor cell lines tested, including those of murine and human origins. The phosphoproteins are associated with the proliferative state of the cell as studied in many systems including growth stimulation of normal lymphoid cells with mitogens, interleukin 2 dependency for growth of a cloned T-cell line, cessation of proliferation by serum starvation of Swiss 3T3 fibroblasts, retention of the proliferative capacity of SV40 transformed 3T3 fibroblasts, and the differentiation and inhibition of proliferation of human promyelocytic leukemic cells. Phosphoproteins with molecular weights of 33,000, 29,000, 23,000, 17,000, and 16,000 are therefore not specific to a particular inducible cellular pathway but are associated with cell proliferation in general. PMID- 3098406 TI - Prevention of dacarbazine damage of human neoplastic cell DNA by aphidicolin. AB - Treatment of human neoplastic cells with dacarbazine both inhibits DNA synthesis and induces damage in the DNA. Lysis of cells in dilute alkali and subsequent electrophoretic analysis of the isolated DNA show that the DNA of treated cells includes a high molecular weight component and a population of 2-10-kilobase single-stranded DNA fragments while untreated cells contain only high molecular weight DNA. When DNA is pulse-labeled at the beginning of the dacarbazine treatment high amounts of small DNA fragments are seen but no labeled high molecular weight DNA. Moreover the DNA fragments are not formed in cells which are treated with aphidicolin before the addition of dacarbazine. Aphidicolin is a specific inhibitor of DNA polymerase alpha, the enzyme responsible for the replicative synthesis of DNA. We conclude that dacarbazine damages DNA only in cells which are synthesizing new DNA. PMID- 3098407 TI - In vitro transformation of mouse mammary epithelial cells grown serum-free inside collagen gels. AB - Mammary epithelial cells from 4-month-old virgin BALB/c mice were cultured inside collagen gels in the following serum-free media: Dulbecco's modified Eagle's medium:Hams's F-12 (1:1) supplemented with: insulin (10 micrograms/ml), bovine serum albumin (5 mg/ml), and epidermal growth factor (5 ng/ml); insulin, bovine serum albumin, progesterone (0.05 microgram/ml), and prolactin (1 microgram/ml); insulin, bovine serum albumin, progesterone, prolactin, and linoleic acid (10 micrograms/ml). Cells proliferated in all these media. The cells were treated with 0.01 micrograms/ml of 7,12-dimethylbenz(a)anthracene or 100 micrograms/ml of N-nitroso-N-methylurea on day 3 of culture and, subsequently, at 1-week intervals for 3-6 weeks. Tetradecanoylphorbol acetate (0.1 micrograms/ml) was added to selected cultures. The cultures were maintained for up to 9 weeks; the cells were then removed from the collagen gels, placed in monolayer culture for 2 days, and removed from monolayer culture, and 5 X 10(5) cells were transplanted to each of the gland-free mammary fat pads of 3-week-old female mice. Approximately 10 weeks after transplantation, the transplanted mammary fat pads were examined for outgrowths. Cells that were not treated with carcinogen and cultured for up to 9 weeks in different serum-free media and transplanted to the gland-free mammary fat pad produced only ductal outgrowths similar in morphology to the ducts of the virgin host's mammary glands. Six treatments with 7,12-dimethylbenz(a)anthracene, of cells grown in the presence of epidermal growth factor, induced 31% spindle cell tumors, 17% ductal hyperplasias, and 5% lobuloalveolar hyperplasias. Cells that were grown in epidermal growth factor and treated three times with N-nitroso N-methylurea produced 23% ductal hyperplasias and 17% lobuloalveolar hyperplasias. Cells grown in the presence of progesterone and prolactin and treated three times with 7,12-dimethylbenz(a)anthracene produced up to 23% lobuloalveolar hyperplasias and 12% ductal hyperplasias. Three treatments with N nitroso-N-methylurea of cells grown in progesterone- and prolactin-containing media produced a maximum of 50% lobuloalveolar hyperplasias and 33% ductal hyperplasias. The lobuloalveolar hyperplasias have the characteristics of the precancerous hyperplastic alveolar nodules found in mouse mammary tumorigenesis. The in vitro carcinogen-induced lobuloalveolar hyperplasias were transplantable, maintained their lobuloalveolar morphology in virgin hosts, and produced carcinomas. PMID- 3098408 TI - Glucocorticoid modulation of plasminogen activators and of one of their inhibitors in the human mammary carcinoma cell line MDA-MB-231. AB - In cultures of the human mammary carcinoma-derived cell line MDA-MB-231, plasminogen activator (PA) activity was reduced substantially following treatment with the glucocorticoid dexamethasone. These cells produced urokinase-type PA (u PA) and tissue-type PA (t-PA), and both enzymes were decreased in dexamethasone treated cultures. The drop in u-PA activity was associated with a decrease in the synthesis of single-chain pro-u-PA and in the concentration of u-PA messenger RNA; however, the decrease in u-PA activity was more extensive than could be accounted for by inhibition of enzyme synthesis only, suggesting that postsynthetic events were also involved. The comparatively small dexamethasone induced decrease in t-PA activity was not associated with a change in the concentration of t-PA messenger RNA. Hence, the two PA genes are differentially regulated by the same hormone. MDA-MB-231 cells also produced a PA-specific inhibitor related to that produced by bovine aortic endothelial cells (PAI-1). This inhibitor was present in two forms: one functionally active, and the other which required activation by sodium dodecyl sulfate; both forms were increased in cultures exposed to dexamethasone. Thus, glucocorticoid-induced inhibition of PA activity in these cells results from a decrease in u-PA synthesis and a concomitant increase in the production of a PA inhibitor. PMID- 3098409 TI - Increase in pO2 and radiosensitivity of tumors by Fluosol-DA (20%) and carbogen. AB - The potential usefulness of i.v. injection of perfluorochemicals and breathing carbogen (95% O2 and 5% CO2) to improve the radiation-induced control of tumors was investigated. When C3H mice, bearing RIF-1 tumors in the legs, were given i.v. injections of Fluosol-DA (20%) at 12 ml/kg, and allowed to breathe carbogen for 1 h before and during a single dose of X-irradiation, the curability of tumors increased by a dose modification factor of 1.47 +/- 0.03 (SE). Such a treatment also increased the radiation-induced skin damage by a factor of 1.15 +/ 0.12, resulting in a therapeutic gain of 1.28 +/- 0.04. Measurement of intratumor pO2 by oxygen microelectrodes demonstrated small increases in pO2 when the animals breathed carbogen, and marked increases in pO2 when Fluosol-DA (20%) was injected into the animals and the animals breathed carbogen. It was concluded that i.v. injection of Fluosol-DA (20%) followed by carbogen breathing significantly improved the oxygen supply to hypoxic cells in the RIF-1 tumors and thus increased the control of tumors by radiation. PMID- 3098410 TI - Inhibition of hamster melanoma growth by estrogen. AB - A malignant hamster melanoma cell line HM-1 derived from the heterogenous malignant hamster melanoma MM1 contains a specific, high affinity binding protein for estrogens. Partial purification of the binding protein with ammonium sulfate (40% saturation) increased mean binding content (3.1 +/- 1.2 (SD) fmol/mg protein) 15-fold without any change in affinity (10(10) M-1). The binding protein sedimented at 8-9S on 10-30% low salt sucrose gradients and 9-10S in the presence of 20 mM molybdate ion. Addition of 0.4 M KCl shifted the 8S peak to 4S. Binding was specific, saturable, and indicative of a single class of high affinity sites over a concentration range of 0.01-10.0 nM [3H]estradiol. Estradiol produced a dose related inhibition of HM-1 growth in vitro without altering the growth of an additional line (HM-2) which did not bind estrogen. The antiestrogen tamoxifen (10(-7) M) also significantly inhibited HM-1 melanoma growth in vitro, which was reversed by the addition of estradiol (10(-9) M). HM-1 xenografts grew faster in female BALB/c-nu/nu mice than male mice while there was no sex difference in HM-2 growth. Pharmacological doses of estradiol and the antiestrogen nafoxidine significantly inhibited HM-1 growth without altering tumor incidence or latency. Our observations suggest that HM-1 cell lines bind estrogens specifically and with high affinity and that hamster melanoma cells positive for this binding protein respond to estrogen. PMID- 3098411 TI - Effects of combined treatments with selenium, glutathione, and vitamin E on glutathione peroxidase activity, ornithine decarboxylase induction, and complete and multistage carcinogenesis in mouse skin. AB - Several structurally different tumor promoters altered to various degrees both glutathione (GSH) peroxidase (EC 1.11.1.9) and ornithine decarboxylase (ODC, L ornithine carboxy-lyase, EC 4.1.1.17) activities in mouse epidermis in vivo. At 5 h after their application to the skin, the complete tumor promoter 12-O tetradecanoylphorbol-13-acetate (TPA) and the stage 2 promoter mezerein were the most potent in inhibiting GSH peroxidase activity and inducing ODC activity. In comparison, the effects of anthralin, phorbol-12,13-didecanoate, benzoyl peroxide, H2O2, and phorbol-12,13-dibenzoate were much smaller, whereas the nontumor promoter phorbol, the hyperplastic agent ethyl phenylpropiolate, and the stage 1 promoter 4-O-methyl TPA did not alter GSH peroxidase and ODC activities. Various treatments including i.p. injections of 40 micrograms of Na2SeO3 and 100 mumol of GSH and/or topical applications of 40 mumol of D-alpha-tocopherol (vitamin E) 20 or 15 min, respectively, before tumor promoter treatment inhibited in an additive manner the effects of either TPA or mezerein on both GSH peroxidase activity and ODC induction. Moreover, these Na2SeO3, GSH, and/or vitamin E treatments inhibited in the same additive manner the tumor-promoting activity of TPA in the initiation-promotion protocol. However, when tested in the 2-stage promotion protocol with 4 doses of TPA followed by twice weekly applications of mezerein, Na2SeO3 plus vitamin E and GSH plus vitamin E treatments inhibited remarkably the tumor-promoting activity of mezerein but were ineffective in the first stage of promotion. The sequence and magnitude for the effects of 7,12-dimethylbenz[alpha]anthracene (DMBA) on GSH peroxidase and ODC activities were very different from those of the tumor promoters. In contrast with their antitumor-promoting activity, the treatments with Na2SeO3 plus vitamin E and GSH plus vitamin E failed to inhibit the carcinogenicity of a single large dose of DMBA and even enhanced the induction of skin tumors by repeated applications of subcarcinogenic doses of DMBA. These results suggest that the promoting component of DMBA carcinogenesis may be different from that of TPA. Moreover, the anticarcinogenicity of Na2SeO3, GSH, and vitamin E may be linked to their ability to facilitate or enhance the activity of the natural GSH-dependent antioxidant protective system of the epidermal cells during the later stages of skin tumor promotion. PMID- 3098412 TI - Effect of drug exposure duration and sequencing on hyperthermic potentiation of mitomycin-C and cisplatin. AB - The effects of drug exposure duration and of heat and drug sequencing on hyperthermic potentiation of mitomycin-C (MMC) and cisplatin (DDP) were studied. Heating for 1 h at 42 degrees C was combined with drug exposure times of 1, 2, 4, or 8 h. For both DDP and MMC, hyperthermic potentiation was greatest when heating was done during drug exposure. Dose enhancement ratios for both drugs at 1% survival were highest with the shortest drug exposure times and decreased as the drug exposure time increased from 1 to 8 h. For DDP, the dose enhancement ratio decreased from 1.9 with a 1-h drug exposure to 1.2 with an 8-h drug exposure. For MMC, the dose enhancement ratio decreased from 1.8 to 1.5 as the drug exposure duration was increased from 1 to 8 h. Our results suggest that thermochemotherapy in vivo is likely to be most effective with rapid infusions of DDP or MMC. PMID- 3098413 TI - Approaches to defining the mechanism of enhancement by Fluosol-DA 20% with carbogen of melphalan antitumor activity. AB - Fluosol-DA with carbogen (95% oxygen and 5% carbon dioxide) breathing can increase the efficacy of melphalan. Addition of Fluosol-DA to treatment with melphalan leads to a greater increase in tumor growth delay under conditions of air breathing and carbogen breathing than does the fat emulsion Intralipid. The ability of melphalan to kill tumor cells increased with dose over the range of drug examined. At the lower doses of drug there is some increase in tumor cell killing seen with the addition of carbogen breathing or Fluosol-DA and air breathing; however, at the highest dose of the drug this difference disappeared. Throughout the melphalan dosage range examined there is approximately 1 log greater tumor cell kill observed with the addition of Fluosol-DA and carbogen breathing compared to the drug treatment alone. There was no significant difference in the survival of bone marrow cells under any of the treatment conditions. Fluosol-DA itself with air or carbogen breathing produced no detectable cross-links in DNA from tumors treated in vivo. The cross-linking factors for melphalan with air or carbogen breathing and for melphalan plus Fluosol-DA and air breathing were similar; when carbogen breathing was added to the treatment combination, the cross-linking factor increased almost 3-fold. When melphalan was dissolved in Fluosol-DA, the melphalan moved quickly into the lipophilic perfluorochemical particles so that after 1 h 60% of the drug was in the perfluorochemical layer. At 24 h, 85-90% of the melphalan was sequestered in the perfluorochemical particles. The pharmacokinetics of [14C]melphalan alone, [14C]melphalan plus Fluosol-DA, and [14C]melphalan prepared in Fluosol-DA were studied in several tissues of FSaIIC fibrosarcoma-bearing mice. In general, the tissue absorption and distribution t1/2s for melphalan were shortened in the presence of Fluosol-DA (except for kidneys). Shifting the t1/2s for absorption and distribution to shorter times produces a much sharper and earlier peak in the drug exposure of the tumor. Fluosol-DA provides a relatively nontoxic means of increasing oxygen delivery to tumors and a therapeutically meaningful way of improving melphalan antitumor activity. PMID- 3098414 TI - Antitumor activity of some bacterial proteases: eradication of solid tumors in mice by intratumor injection. AB - A protease isolated from the culture filtrate of a Gram-negative bacteria, Serratia marcescens kums 3958, showed very potent antitumor activity when injected into Meth-A or RL male 1 tumors in BALB/c mice at 30 micrograms per tumor or more. This and certain other proteases, which are resistant to many protease inhibitors in plasma, appear to be new candidate drugs for regional treatment of solid tumors. PMID- 3098416 TI - Identification of 5-S-cysteinyldopa by high performance liquid chromatography in biopsies from patients with dysplastic melanocytic nevi. AB - The appearance of 5-[(L)-S-cysteinyl]dopa, a major product in pheomelanogenesis was examined in affected and nonaffected skins from 20 patients with clinical signs of dysplastic melanocytic nevi. Analysis by high performance liquid chromatography and electrochemical detection showed that 20 of the 35 lesions had a pathological formation of 5-[(L)-S-cysteinyl]dopa (0.04-28.86 ng/micrograms acid soluble protein). 5-[(L)-S-cysteinyl]dopa was not detected in any of the normal uninvolved skin samples analyzed. PMID- 3098415 TI - Endocrine effects of adjuvant chemotherapy and long-term tamoxifen administration on node-positive patients with breast cancer. AB - Ovarian and pituitary hormones were determined in pre- and postmenopausal breast cancer patients before and at intervals during adjuvant chemotherapy or chemotherapy plus tamoxifen (TAM). Chemotherapy did not affect gonadotrophin levels in postmenopausal patients; however, inclusion of TAM in the regimen produced a partial (approximately 50%) reduction in circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone. Gonadotrophin levels remained reduced as long as TAM therapy continued, at which time they rose to postmenopausal values. Chemotherapy (6-12 months) caused ovarian failure in premenopausal patients with decreases in estrogen (estrone plus estradiol) and rises in gonadotrophin levels to postmenopausal levels. Inclusion of TAM in the regimen caused an initial 3-fold rise in peak circulating estrogen levels before ovarian failure (6-9 months of therapy). Some younger patients (approximately 40 years of age) who had a short course (4 months) of chemotherapy plus TAM followed by continuous TAM therapy alone resumed ovulatory menstrual cycles. Estrogen, progesterone, and follicle-stimulating hormone levels were increased compared with control subjects. Those patients who experienced ovarian failure with adjuvant chemotherapy plus TAM only had a partial rise in gonadotrophins compared with patients receiving chemotherapy alone. TAM maintained the levels of gonadotrophins for as long as therapy was administered, at which time they rose to postmenopausal levels. Although TAM exhibited estrogen-like effects on gonadotrophins there was no estrogen-like increase in circulating prolactin levels in either pre- or postmenopausal patients. One patient experienced an estrogen receptor-positive recurrence during long-term tamoxifen therapy. Serum levels of tamoxifen and metabolites declined in the year prior to the recurrence and this was associated with a rise in gonadotrophins. This indicated noncompliance by the patient. Compliance can be monitored either directly with serum levels of TAM or by serial gonadotrophin determinations. We suggest that the optimal antitumor activity of TAM will be achieved in a low estrogen environment with continuous high levels of the drug in the serum. We recommend that patients undergoing long-term TAM therapy be monitored for complete ovarian failure and drug compliance. PMID- 3098417 TI - Phase I study of i.v. administered recombinant gamma interferon in cancer patients. AB - We report a phase I study of the biological effects, tolerance, and pharmacokinetics of 6- and 24-hour iv infusions of recombinant interferon-gamma (rIFN-gamma) in cancer patients. Twenty-one patients received the 6-hour iv infusion regimen at doses ranging from 0.016 to 0.65 mg/m2/day. Forty-one patients received the 24-hour iv infusion regimen at doses ranging from 0.01 to 0.05 mg/m2/day. Fever and flu-like symptoms were the most common side effects and were seen at all dose levels. The maximum tolerated dose was 0.16 mg/m2 for the 6 hour regimen and 0.01 mg/m2/day for the 24-hour regimen. A dose-dependent granulocytopenia was observed at doses greater than or equal to 0.05 mg/m2/day. A marked increase in beta2 microglobulin occurred by Day 5 of treatment in almost all patients, regardless of the dose level. Consistent serum levels of rIFN-gamma were achieved only at doses of 0.325 mg/m2/day of the 6-hour infusion. The mean serum concentrations at this dose ranged from 18 to 83 units/ml as measured by bioassay (0.64-2.4 ng/ml by enzyme-linked immunoassay). Antibody against rIFN gamma did not develop in any patient. During the short period of evaluation of this study, one patient with renal cell carcinoma achieved a partial response, and three patients with renal cell (two) and lung carcinoma (one), respectively, achieved minor responses. This study will form the framework for phase II efficacy trials of iv rIFN-gamma. PMID- 3098419 TI - Improvement in cardiac ectopy during gamma interferon infusion: a case report. PMID- 3098418 TI - Effect of cimetidine and ranitidine on the metabolism and toxicity of hexamethylmelamine. AB - In a rat model, doses of 20-120 mg/kg of cimetidine prolonged in a dose-related manner the half-life of hexamethylmelamine by 29%-80%, while doses of 1-25 mg/kg of ranitidine did not. Administration of 120 mg/kg of cimetidine with a single 350-mg/kg dose of hexamethylmelamine increased toxicity from LD30 to LD75 (P = 0.005). When combined with 25 mg/kg of ranitidine, a statistically insignificant (P = 0.16) 15% increase in hexamethylmelamine toxicity was noted. These studies indicate that cimetidine but not ranitidine increases the toxicity of hexamethylmelamine through inhibition of microsomal metabolism. PMID- 3098420 TI - The effect of carbon dioxide laser irradiation on cranial bone healing. An experimental study. AB - An experimental study on the effects of carbon dioxide laser irradiation osteotomy of the calvarium of 4-week old rabbits was compared with tht of an osteotomy performed with a high speed drill. Histological studies of calvarium cross sections were performed at 2, 4 and 6 weeks following the osteotomies. As early as 2 weeks following high speed drill osteotomy connective tissue bridged the bone edges. By 4 weeks this bridge was thickened and endowed with numerous vessels. At 6 weeks numerous osteoblasts lined the bone edge and connective tissue bridge. Following laser osteotomy the carbonized edges interrupted the connective tissue from bridging the bone edges at 2, 4 and 6 weeks. By 6 weeks following the laser osteotomy connective tissue had grown past the carbonized residue and the healing process proceeded with osteoblast proliferation from points beyond the carbonized residue. The significance of these findings in reference to the reossification process following osteotomies for craniosynostosis and craniofacial surgery, is discussed. PMID- 3098421 TI - Monomer sequence and acetylation pattern in some bacterial alginates. AB - The sequential structures and acetylation patterns of alginates from several strains of Azotobacter vinelandii and Pseudomonas species, including P. aeruginosa, P. putida, P. fluorescens, and P. mendocina, have been studied by 1H n.m.r. spectroscopy. O-Acetyl groups were exclusively associated with the D mannuronic acid residues and the degree of acetylation varied in the range 4-57%, depending upon the proportion of this acid in the polymer. 1H-N.m.r. spectroscopy of a naturally occurring and an artificially acetylated D-mannuronan made it possible to determine the degrees of acetylation at O-2, O-3, and O-2,3. The most conspicuous difference between alginates from A. vinelandii and the four Pseudomonas species was the complete absence of consecutive L-guluronic acid residues in the latter. PMID- 3098422 TI - Synthesis of p-nitrophenyl beta-D-galactofuranoside. A convenient substrate for beta-galactofuranosidase. PMID- 3098423 TI - Release of inorganic sulfate ion under mild alkaline conditions from sulfated, unsaturated disaccharides obtained from chondroitin sulfates by chondroitinase digestion. PMID- 3098424 TI - [Electrophysiologic effects of intravenous and oral encainide in patients with Wolff-Parkinson-White syndrome and paroxysmal atrial fibrillation]. PMID- 3098425 TI - Gastric effects of a prostaglandin E1-derivate (rioprostil) on acid, alkaline, and mucus secretion. AB - In a double-blind crossover study, the gastric effects of a single oral dose of rioprostil (150 and 300 micrograms) or placebo were compared in basal conditions and during a 120-minute pentagastrin infusion. A slight decrease in basal acid output and a nonsignificant rise in basal bicarbonate secretion were observed with the 300-micrograms dose. Pentagastrin-stimulated acid secretion was reduced by the prostaglandin derivate, especially with the 300-micrograms dose. Compared with placebo, 300 micrograms of rioprostil significantly stimulated basal mucoprotein secretion and bicarbonate and mucus output during pentagastrin infusion. The results suggest that 300 micrograms of rioprostil exerts both a moderate antisecretory activity and a strengthening effect on the gastric mucus bicarbonate barrier. PMID- 3098426 TI - In vitro activity of piperacillin, ticarcillin, mezlocillin, ticarcillin clavulanic acid, aztreonam, ceftazidime, azlocillin, cefoperazone, and thienamycin against Pseudomonas aeruginosa. AB - The in vitro susceptibility of 103 well-characterized strains of Pseudomonas aeruginosa to nine antimicrobial agents was assessed by means of the Kirby-Bauer disk diffusion assay and the microtiter minimal inhibitory concentration assay. The antimicrobials, from the most to the least active against P aeruginosa, were thienamycin greater than ceftazidime greater than piperacillin greater than azlocillin greater than cefoperazone greater than aztreonam greater than ticarcillin greater than ticarcillin-clavulanic acid greater than mezlocillin. The resistance patterns of the antimicrobial agents suggest that P aeruginosa resistant to a penicillin, cephalosporin, or aztreonam may be susceptible to thienamycin. PMID- 3098427 TI - Comparison of two transdermal nitroglycerin systems. AB - In a study conducted by office-based cardiologists at eight sites, 115 patients using transdermal nitroglycerin for treatment of angina pectoris participated in a four-week comparison of two transdermal nitroglycerin patches: Transderm-Nitro (TDN) and Nitro-Dur II (ND II). Patients wore two patches, one of each brand, each with half their normal prescribed daily dose of 10 mg (release rate per 24 hours) to compare patch adherence properties, patient preference, and local side effects. More ND II than TDN patches fell off (5% versus 0.1%), and fewer TDN than ND II patches became loose (1.7% versus 8.4%); 98.2% of the TDN and 86.7% of the ND II patches adhered totally. Significantly more patients expressed a preference for TDN over ND II in four of eight assessment variables, including the choice of their next prescription. The frequency of problems at the site of patch application was similar with both patches. PMID- 3098428 TI - Cimetidine and parenteral nutrition in the ICU patient. AB - Cimetidine is often prescribed for hospitalized patients requiring intravenous nutritional support (ie, total parenteral nutrition). When administered parenterally, the drug may prevent excessive fluid and electrolyte loss in patients with short-bowel syndrome, particularly after resection. It may also help prevent anastomotic ulcers in patients following partial gastrectomy. In patients with hypersecretory disease or high-volume ostomy drainage, cimetidine is clinically useful in moderating secretions, thus reducing fluid and electrolyte loss. Cimetidine can prevent, and perhaps treat, metabolic alkalosis associated with significant losses of nasogastric aspirate. Intravenous administration of the drug to patients requiring nasogastric suction often eliminates the need for addition of hydrochloric acid to their parenteral nutrition admixtures. Cimetidine has been found to be physically compatible and chemically stable in crystalline amino acid/dextrose solutions and in crystalline amino acid/dextrose/lipid admixtures. As cimetidine is widely used in patients receiving total parenteral nutrition, it has become acceptable practice to deliver the drug via parenteral nutrition admixtures. Admixing the drug may be of particular advantage for patients with limited vascular access or for those who are fluid restricted. Cimetidine when given by continuous infusion may be more effective and require less drug per day than if administered via intermittent injection. Moreover, administration of cimetidine by continuous infusion to hyperalimentation patients has been documented to save the institution more than $22,000 a year in materials and labor costs. PMID- 3098429 TI - Morphological aspects of experimental dentinal caries in rats. PMID- 3098430 TI - Haematological cell proliferation and differentiation responses to perturbations of polyamine biosynthesis. AB - Combined administration of methylglyoxal-bis-guanylhydrazone (MGBG) (25 mg/kg) with difluoromethylornithine (DFMO), or MGBG alone at a higher dose (50 mg/kg), to mice resulted in a decreased white cell count (WBC) in the peripheral blood while DFMO or MGBG alone at a lower dose (25 mg/kg) had no effect. As expected, DFMO alone increased the number of colony forming units spleen (CFU-s), colony forming units diffusion chamber granulocyte (CFU-dg) and colony forming units culture (CFU-c) in the bone marrow. MGBG treatment led to an increase in CFU-dg alone. Combined treatment seemingly had no effect on marrow stem cells. Total tibial and differential counts were not affected by any of the treatments. Cell proliferation in diffusion chamber cultures, as judged by CFU-dg colony formation, was impaired by MGBG alone or in combination with DFMO, at dose levels which had no effect or increased the precursor cell number in the bone marrow. This effect was partially reversed with either putrescine or spermidine. Determination of intracellular polyamine concentrations, demonstrated decreased putrescine and spermidine levels after DFMO administration. As expected, MGBG treatment resulted in decreased spermidine and spermine levels, concomitant with an increase in putrescine. In mice which received both agents, rather than only MGBG, after 3 days higher intracellular polyamine concentrations were observed. After 11 days, however, there was no significant difference between the two groups. PMID- 3098431 TI - Ultrastructure of capitate projections in the optic neuropil of Diptera. AB - Photoreceptor axons in the first optic neuropil of the dipteran flies Musca domestica and Drosophila melanogaster was examined with electron microscopy. The objective was to determine ultrastructure, persistence and glial source of the capitate projections found within these neurons. Capitate projections are simple or compound processes of epithelial glial cells which profusely insert into form fitting folds of axon terminals of the peripheral retinular cells (R1-6) in the synaptic plexus portion of the first optic neuropil. These neuro-glial junctions may be simple indentations, have a head with a single stalk, or possess a single, circular stalk from which 3 or 4 bulbous (glial) heads are elaborated. Using serial thick sections of Drosophila neuropil for HVEM we were able to observe that the stalks connecting nearly all capitate projections led directly to a glial cell. Thus no disembodied heads were found suspended in axoplasm. Capitate projections appeared to be persistent structures, present in young as well as senescent adults. No evolution of form was found; thus 3 distinct expressions of these glial processes (without transitional forms) are present. From freeze fracture replicas and serial HVEM sections it was determined that there were approximately 3 capitate projections per micron 2 in Drosophila and Musca, respectively. About 800 capitate projections exist per Musca axon terminal or about 5 times the number of chemical synapses. Cp's were slightly larger in Drosophila than in Musca, although the Musca retinular axon has twice the diameter and length of that of the fruit fly. The evidence was reviewed in light of the likely supportive function of capitate projections on the R1-6 terminals. PMID- 3098432 TI - Platelets and prostaglandins. PMID- 3098433 TI - Naproxen (Naprosyn). Pharmacokinetics: therapeutical relevance and tolerance profile. PMID- 3098434 TI - Pharmacokinetics of naproxen sodium. AB - Naproxen sodium is a drug characterized by rapid and complete absorption after oral administration, highly protein-bound distribution, relatively simple metabolism, and renal excretion. Its pharmacokinetics are little affected by food, by dosage levels (within wide limits), or by mild renal impairment. The main mechanism of naproxen sodium action, inhibition of prostaglandin synthesis, makes the drug effective in combating pain and inflammation, while its relatively long half-life permits a two times daily dosing. The drug is well tolerated by most patients. PMID- 3098435 TI - The role of the kappa enhancer and its binding factor NF-kappa B in the developmental regulation of kappa gene transcription. AB - We report here on a comparison of plasmacytoma cell lines that differ markedly in their ability to express kappa immunoglobulin genes introduced by transfection, but nevertheless express their endogenous kappa genes at comparable levels. The cell line that fails to express exogenous kappa genes is nonpermissive for kappa enhancer function, apparently because it lacks a specific kappa enhancer-binding nuclear factor (NF-kappa B). We show that this same nuclear factor is also lacking in pre-B cells and that treatment of these cells with bacterial lipopolysaccharide induces the appearance of NF-kappa B in nuclear extracts and concomitantly activates the kappa enhancer. These findings indicate that factor NF-kappa B controls kappa enhancer activity, and that this activity is only transiently required during B cell maturation. PMID- 3098436 TI - Functional domains of Pseudomonas exotoxin identified by deletion analysis of the gene expressed in E. coli. AB - Pseudomonas exotoxin A is a single chain toxin with three structural domains that inhibits protein synthesis in eukaryotic cells by catalyzing ADP ribosylation of elongation factor 2. To study the function of these domains, we deleted different portions of the PE structural gene and expressed these constructs in E. coli using an inducible T7 promoter. These studies indicate that structural domain Ia is required for cell recognition, that structural domain II is required to translocate the toxin across a cellular membrane, and that structural domain III and a portion of domain Ib are required for ADP ribosylation activity. Toxin lacking domain Ia is about 100-fold less toxic to mice than intact PE and should be a useful molecule for the construction of immunotoxins. PMID- 3098437 TI - Structure of the human and murine R-ras genes, novel genes closely related to ras proto-oncogenes. AB - The human R-ras gene was isolated by low-stringency hybridization with a v-H-ras probe. The predicted 218 amino acid R-ras protein has an amino-terminal extension of 26 residues compared with H-ras p21, and shows 55% amino acid identity; conserved domains include the p21 GTP-binding site and the carboxy-terminal membrane localization sequence. R-ras has at least six exons, with the position of the first intron conserved relative to the Drosophila ras64B and Dictyostelium ras genes; there is no similarity in the exon-intron structure of the R-ras gene and of the mammalian H-, K-, and N-ras proto-oncogenes. Cloned mouse R-ras cDNAs exhibit 88% nucleotide and 94.5% predicted amino acid identity to human R-ras. Human R-ras was localized to chromosome 19, a site different from ras p21 genes. Mouse R-ras is syntenic with c-H-ras on chromosome 7. PMID- 3098438 TI - Immunochemical subfractionation of a microsomal fraction of rat liver with antibody-coated Staphylococcus aureus cells. AB - The procedure for immunochemical adsorption of vesicles with specific antigen on their outer surfaces was improved. When microsomal vesicles were mixed with Staphylococcus aureus cells coated with the antibody against NADPH-cytochrome c reductase, more than 90% of the enzyme activity was adsorbed on the cell, whereas, only about 10% of the activity was adsorbed on cells coated with the same amount of anti-ovalbumin antibody. NADH-cytochrome c reductase and aldehyde dehydrogenase activities were adsorbed on the cell to the same extent as was NADPH-cytochrome c reductase activity. Under this condition, there was no adsorption of the activities of the marker enzymes of lysosomes and Golgi apparatus, whereas large amounts of the activities of the plasma membrane enzymes were adsorbed. The specific activity of NADPH-cytochrome c reductase in the adsorbed vesicles from the microsomal fractions increased considerably. In contrast, marker enzymes of the Golgi or of the plasma membranes could be enriched in unadsorbed vesicles from the Golgi fractions. PMID- 3098439 TI - [The final picture of wound healing in CO2 laser scalpel surgery]. AB - The terminal reparative phase was studied in wounds caused by carbon dioxide laser on rat skin, auricle, striated muscle, liver and spleen. Comparative histology was especially concerned with resorptive granulomas around carbonized tissue remnants. Presence of carbonized residua was connected with a more extensive fibrosis and seemed to lengthen the healing process. PMID- 3098440 TI - Susceptibility of enterococci. I. Inhibitory and bactericidal activity of several chemoantibiotics against Streptococcus faecalis and Streptococcus faecium. AB - The authors present a microbiological study of 100 strains of Enterococcus (70 strains of Streptococcus faecalis and 30 strains of Streptococcus faecium) tested for susceptibility to the following antibiotics, amoxicillin, ampicillin + flucloxacillin, piperacillin, rifampicin, vancomycin, netilmicin, ofloxacin, and norfloxacin. The assessment of minimum inhibitory and minimum bactericidal concentrations of these substances indicates that all have good inhibitory activity except netilmicin, which is active at higher concentrations; with rifampicin and vancomycin showing very poor bactericidal activity. The bactericidal activity of penicillins was hard to assess because of tolerance and paradoxical effect phenomena. The quinolones showed good inhibitory and bactericidal activity. PMID- 3098442 TI - Synthesis of a new amino acid-antibiotic, oxetin and its three stereoisomers. PMID- 3098441 TI - Susceptibility of enterococci. II. Inhibitory and bactericidal activity of drugs in combination against Streptococcus faecalis and Streptococcus faecium. AB - The microbiological utility of antibiotic combinations against Streptococcus faecalis and Streptococcus faecium strains was studied. The drugs used were netilmicin + amoxicillin (20 strains); netilmicin + piperacillin (20 strains); netilmicin- + vancomycin (20 strains); netilmicin + rifampicin (20 strains). Netilmicin used in combination with the penicillins was advantageous against Streptococcus faecalis, but not uniformly against Streptococcus faecium. The combinations of netilmicin with vancomycin or rifampicin were no more effective than the single drugs in most cases, although the response varied for the different strains of the two species. PMID- 3098443 TI - The synthesis and antitumor activities of tropolone and 8-hydroxyquinoline derivatives. PMID- 3098444 TI - Superior efficacy of trimelamol to hexamethylmelamine in human ovarian cancer xenografts. AB - A series of eight human ovarian cancer lines grown in nude mice were used to compare the activity of hexamethylmelamine (HMM) and N2,N4,N6-trihydroxy methyl N2,N4,N6-trimethylmelamine (trimelamol). The tumor lines differed in histological subtype and growth rate. The drugs were administered i.p. at the maximum tolerated dose at alternate days. Differences in volume of treated and control tumors were endpoints of the study. The tumor lines varied widely in sensitivity to HMM and in four lines a T/C% below 25% was achieved. Trimelamol appeared to be more active than HMM and achieved a T/C below 25% in seven tumor lines. Thus far, the drug has demonstrated significant activity in a phase I trial in ovarian cancer patients. Comparative clinical studies of HMM vs trimelamol have not yet been performed. PMID- 3098445 TI - The first clinical use of depot buserelin for advanced prostatic carcinoma. AB - The agonist analogues of the gonadotrophin-releasing hormone now provide an alternate medical treatment of prostatic cancer. For effect repeated administration is required, either by five or six times daily intranasal or once daily subcutaneous treatment. There is an obvious disadvantage to such regimens in elderly patients who may have difficulty complying with therapy. In order to circumvent these difficulties, sustained release formulations of the agonist analogues have been synthesized. We report the first clinical use of a long acting formulation of D-Ser (TBU)6-LHRH Ethylamide (buserelin) using a novel polymer material. Twelve symptomatic patients with previously untreated carcinoma of the prostate were treated with depot buserelin, administered once monthly. In all patients, depot buserelin suppressed serum testosterone into the range seen in castrate men at a rate equivalent to that provided by five times daily intranasal therapy. No significant increase in serum testosterone, luteinizing hormone or follicle-stimulating hormone concentrations occurred during the period of follow-up. Long-acting formulations of buserelin offer an advance in the management of prostatic cancer with agonist analogues of the gonadotrophin releasing hormone. PMID- 3098446 TI - [Experimental observation on the latex agglutination test in the detection of anti-schistosome antibody]. PMID- 3098447 TI - The economics of heart transplantation. PMID- 3098449 TI - Stimulation of IgE sensitized human alveolar macrophages by anti-IgE is unaffected by sodium cromoglycate. AB - Sodium cromoglycate is an effective prophylactic in the treatment of asthma. However, its mechanism of action is still uncertain. The release of thromboxane B2 and N-acetyl-beta-D-glucosaminidase activity was measured from human alveolar macrophages sensitized with human myeloma IgE. Cells were challenged with rabbit affinity purified anti-IgE (no activity against IgG) in the absence or presence of sodium cromoglycate (10(-4)-10(-8)M). There was no change in the release of either thromboxane B2 or N-acetyl-beta-D-glucosaminidase in the presence of sodium cromoglycate at these concentrations. PMID- 3098448 TI - Bacterial adherence to contact lenses. PMID- 3098450 TI - Gastrointestinal permeability in children with cow's milk allergy: effect of milk challenge and sodium cromoglycate as assessed with polyethyleneglycols (PEG 400 and PEG 1000). AB - Sixteen children with immediate-type cow's milk allergy were challenged with increasing amounts of cow's milk. Gastrointestinal permeability was investigated before and after challenge by the 6-hr urinary recovery of a mixture of different sized polyethyleneglycols (PEG 400 and PEG 1000). The results were related to clinical symptoms in the individual patients. The majority of the children displayed changed permeability characteristics after the challenge, both with respect to the maximum uptake of a small test molecule (usually 370 dalton PEG) and/or a large molecule (1074 dalton PEG), and to size-dependent exclusion of probe molecules. When corrected for the dose of milk taken, the children showing the most severe immediate-type symptoms also displayed the greatest alteration of permeability. Treatment with sodium cromoglycate (SCG) before the challenge diminished the effect on the uptake of probe molecules, usually decreased the severity of elicited symptoms, allowing about a ten-fold increase in the milk dose. Cow's milk challenge in healthy children caused only minor permeability changes, whereas challenge in the sensitized subjects significantly changed (increased or decreased) the recovery of a large test molecule. The difference between healthy and allergic subjects was most obvious when correcting for dose of milk ingested. We conclude that oral challenge with cow's milk in allergic subjects affects the mucosal barrier, and peroral treatment with SCG moderates immediate hypersensitivity reactions with respect to both tolerated antigen dose and intestinal permeability properties. PMID- 3098451 TI - Mitochondrial aspartate aminotransferase linked to immunoglobulin G of the kappa lambda type: report of a case. AB - Macromolecular aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase EC 2.6.1.1, AST) was found in the serum of a patient with benign hypertension. The serum total AST and mitochondrial AST (mAST) activities were proportionately higher. The abnormal AST was found to be a macromolecular complex composed of mAST and immunoglobulin G of the kappa-lambda type. The dissociated IgG from the complex was shown to combine with human and rat mAST, but not with cytosolic AST of both species. Molecular mass of the macromolecular AST was estimated to be 360,000 Da. These results indicate that the complex may consist of one IgG molecule associated with two mAST molecules. By the method of papain digestion the binding site of immunoglobulin in the complex appeared to be located in the Fab portion of the IgG molecule. This finding strongly suggests that the AST-immunoglobulin complex is a specific antigen-antibody complex. PMID- 3098452 TI - A practical approach to light chain typing in monoclonal gammopathy. PMID- 3098453 TI - 3,5-Diiodotyrosine and thyronine in the urine of patients with chronic renal disease. AB - Urinary 3,5-diiodotyrosine (DIT) and thyronine (T0) excretion was investigated in 18 patients with chronic renal disease. In accord with previous findings serum T4 and thyroid hormone binding proteins measured in 17 patients were in the low or normal range. Urinary albumin excretion was elevated in all 18 and T4 binding prealbumin (TBPA) in 15 of the 18. Urinary T0 excretion measured in 12 patients was also significantly lower than normal (mean +/- SD 4.4 +/- 2.6 vs 15.8 +/- 5.8 nmol/24 h renal vs normal 2 P less than 0.001). In contrast urinary DIT excretion was significantly elevated in renal patients compared with normal subjects (2.0 +/- 1.5 vs 0.75 +/- 0.41 nmol/24 h, respectively). Possible sources of the increased DIT are discussed. PMID- 3098454 TI - Interactions of oestradiol benzoate and promegestone upon basal and TRH-induced prolactin secretion in postmenopausal women. AB - The interactions of ovarian steroids with PRL secretion in women are still controversial. Ten healthy postmenopausal women, on no medication, received during the first period of 2 months later in a cross-over design study, i.m. injections of 0.625 mg of oestradiol benzoate (EB) alone for 10 d or in combination with 750 micrograms/d of a pure progestin promegestone for 10 d. A TRH (200 micrograms i.v.) stimulation test was performed before the start and at the completion of each treatment period. Basal plasma gonadotrophins, PRL and oestradiol were measured every day by radioimmunoassay. The EB-induced rise in oestradiol levels was similar during the two periods. In response to EB treatment serum PRL levels increased from 6.1 +/- 0.9 ng/ml to 22.9 +/- 3.4 ng/ml. With the addition of promegestone, the increase in PRL, from 6.7 +/- 1.3 ng/ml to 13.8 +/- 2.5 ng/ml, was significantly diminished (P less than 0.001). The PRL release induced by TRH was significantly greater with EB treatment than was the response with the combined treatment (P less than 0.05, Wilcoxon test to compare the areas under the curves). These data suggest that in postmenopausal women oestrogens act as stimulators of PRL release and promegestone is able to partially counteract the stimulatory effect of oestradiol benzoate upon basal and TRH-stimulated PRL secretion. PMID- 3098455 TI - Does testosterone affect the normal menstrual cycle? AB - In order to throw further light on the role of androgens in the aetiology of the polycystic ovary syndrome (PCO) we have examined the effect of artificially increasing serum testosterone levels on menstrual function in a group of ovulating women. Six women were studied who had either severe premenstrual syndrome or loss of libido for which they were treated with 100 mg testosterone by s.c. implantation. All had regular menstrual cycles. For 1 month before implantation serum LH, FSH, oestradiol (E2), progesterone and testosterone were measured three times per week. All women showed normal cyclical variation of LH, FSH, E2 and progesterone. Following implantation, three times weekly blood samples were taken during the first and third cycles. No patient had any disturbance of menstrual pattern. All continued to show cyclical changes of LH, FSH, E2 and progesterone. Serum E2 and progesterone were lower but not significantly so in the luteal phase of the treated cycles. This was despite a mean serum testosterone which rose from 1.3 to 7.1 nmol/l at the end of the third week following implantation and to 4.1 nmol/l at the end of the third month. Sex hormone binding globulin levels fell as expected by 18.5% during the first cycle. The lack of significant effect of a markedly elevated serum testosterone level on cyclical hormone changes is indirect evidence that in PCO the primary cause of the menstrual disturbance is not excessive production of ovarian or adrenal testosterone. PMID- 3098456 TI - Hypothalamic hypopituitarism following cranial irradiation for nasopharyngeal carcinoma. AB - Eight patients, one male and seven females, with no pre-existing hypothalamic pituitary disease, who developed symptoms of hypopituitarism following cranial irradiation for nasopharyngeal carcinoma were studied 5 years or more after radiotherapy. All were GH deficient. Four of the patients with no GH response during insulin tolerance tests (ITT) showed increased GH in response to synthetic human growth hormone releasing factor (GRF-44). Four patients had impaired cortisol responses to ITT, and gradual but diminished cortisol responses to ovine corticotrophin releasing factor (CRF-41). There was no significant difference between mean peak increments in response to ITT and those in response to CRF-41. TSH responses to TRH were delayed in five and absent in two patients; four of these had low free T4 index. Prolactin was raised in all seven women and increased further in response to TRH. Two patients had impaired gonadotrophin responses to LHRH. None of the patients had clinical or biochemical evidence of diabetes insipidus. These data suggest that post-irradiation hypopituitarism in these patients results from radiation damage to the hypothalamus leading to varying degrees of deficiency of the hypothalamic releasing or inhibitory factors. PMID- 3098457 TI - The long-term effects of megavoltage radiotherapy as sole or combined therapy for large prolactinomas: studies with high definition computerized tomography. AB - The long-term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6-22 years (mean 13 years). Galactorrhoea was abolished in four of the five females with this symptom, but menstrual disturbance persisted in five of six patients. Sexual function was normal without sex hormone replacement in only one of the eight males after treatment. Neurological deficits were abolished or improved by treatment in all 9 patients with this presentation. Serum prolactin levels declined after treatment (P less than 0.001) and fell to within the normal range off bromocriptine therapy in six of the 14 patients at a mean of 9 years (range 5-17 years) after radiotherapy. All patients had anterior pituitary deficiency of some degree at reassessment, and 13 required replacement treatment. Serial skull radiographs revealed remineralization of the fossa floor in five patients and a decrease in fossa size in three. All five patients who did not also have surgery had evidence of tumour shrinkage without bromocriptine treatment (on CT scan or metrizamide cisternography). Fourth generation CT scans on completion of the study revealed a decrease in tumour mass in all patients, with varying degrees of empty sella in 13 and a cystic intrasellar tumour in the remaining one. Residual tumour was demonstrated in 10 patients, three of whom had normal serum prolactin levels, while one patient without visible tumour had persistent hyperprolactinaemia. Radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume. PMID- 3098458 TI - Growth hormone responses to GRF 1-29 in patients with primary hypothyroidism before and during replacement therapy with thyroxine. AB - It is well known that hypothyroidism is frequently associated with impaired GH responses to different stimuli. In the present study we have evaluated GH responses to GH-releasing factor (GRF) in patients with primary hypothyroidism before and during T4 replacement therapy. Fourteen patients (age range 26-60 years) underwent two GRF tests (1 microgram/kg) before and during replacement therapy (150 micrograms/d). Administration of T4 increased peak GH responses to GRF in 9 patients and in the group as a whole (mean +/- SEM, 17.0 +/- 2.8 vs 32.6 +/- 5.7 mU/l, P less than 0.02). When the data are analysed by means of area under the curve (AUC), the GH response to GRF was increased by T4 in 10 patients and in the group as a whole (mean +/- SEM, 51.7 +/- 14.3 vs 101.5 +/- 28.1, P less than 0.02). These data indicate that thyroid hormone replacement therapy enhances the responsiveness of the somatotroph to GRF 1-29 in patients with primary hypothyroidism. PMID- 3098459 TI - Nocturnal pulsatile growth hormone releasing hormone treatment in growth hormone deficiency. AB - We have treated five GH-deficient prepubertal children (4 M, 1 F) with GH releasing hormone 1-40 (GHRH1-40) in two dosage regimens over 9 months. Profiles of serum GH concentrations were obtained over 24 hours before treatment and nocturnal profiles were obtained serially throughout the study. GHRH was administered subcutaneously at night for four pulses using 1 microgram/kg/pulse in the first 3 months and 2 micrograms/kg/pulse for a further 6 months. All subjects demonstrated pituitary responsiveness to i.v. GHRH before treatment and at 3 and 6 months. GH secretion was induced in a pulsatile fashion in response to subcutaneous GHRH in three children from the first night of treatment. A self priming effect to successive GHRH pulses was evident and the response augmented with time and with the higher dose regimen. The growth velocity of these three children increased from a mean of 3.7 cm/year (range 3.7-3.8) before treatment to 5.5 cm/year (range 4.1-7.2) over the first 3 months and to 7.2 cm/year (range 4.8 9.2) over the following 6 months. In one subject entrainment of GH secretion to GHRH did not occur until the higher dose regimen and this was associated with a modest increase in growth velocity. One subject did not respond to treatment. Pulsatile administration of GHRH1-40 is effective in inducing GH secretion and promoting growth acceleration in some children with idiopathic GH deficiency. The optimal dose and mode of administration of GHRH have yet to be established. PMID- 3098460 TI - Alterations in the hypothalamic-pituitary-thyroid axis after prolonged residence in Antarctica. AB - The human population which lives and works in polar environments has been increasing steadily over the last 15 years. Very little is known about how these residents adjust to their environment. Cold adaptation in man is a poorly understood phenomenon. Euthermic mammals maintain body temperature during cold exposure via non-shivering thermogenesis, a process which is hormonally mediated. We studied prospectively the response of the hypothalamic-pituitary-thyroid axis in 17 euthyroid men before, during and after assignment to duty in the Antarctic. Serum total and free T4 levels fell slightly but not significantly after very prolonged Antarctic residence. Serum total and free T3 decreased significantly from basal levels of 170 +/- 3 ng/dl and 388 +/- 19 pg/dl to 155 +/- 5 ng/dl and 319 +/- 14 pg/dl respectively after Antarctic duty. Serum T3 levels increased after 42 weeks of polar living, the end of the observation period, but the change did not attain statistical significance. The integrated TSH response to TRH administration increased by 50% to 734 +/- 58 microIU.min/ml over warm climate basal response levels of 456 +/- 33 microIU.min/ml by the end of the study. The daily circadian rhythm of serum cortisol was maintained throughout the study period. The alterations in thyroid hormones which we describe, are apparently related to the chronic cold exposure which our subjects experienced in this polar environment. PMID- 3098461 TI - Effect of the anti-thyroid drug methimazole on interleukin-1 and interleukin-2 levels in vitro. AB - There is now good evidence that anti-thyroid drugs such as methimazole have immunomodulatory effects which may be important in the treatment of patients with Graves' disease, but the immunological mechanisms by which these agents act are not clear. This study has examined the effect of methimazole on four important soluble mediators of the immune response, interleukin-1 (IL-1), interleukin-2 (IL 2), gamma-interferon (gamma-IFN) and B-cell differentiation factor (BCDF). When peripheral blood mononuclear cells from normal subjects were stimulated with mitogens (phytohaemagglutinin, concanavalin A or pokeweed mitogen) in the presence of 10-100 mumol/l methimazole, there was an increase in IL-2 activity in the culture supernatants. This effect was apparent between 24 and 60 h: enhanced proliferation of T-cells was also seen in methimazole-supplemented cultures. There was no effect of the drug on IL-2 receptor expression or on IL-1 and gamma IFN production. BCDF was increased by methimazole in one of three experiments with pokeweed mitogen but not in three experiments with concanavalin A. These results suggest that the enhancement of mitogen-stimulated T-cell proliferation in vitro with methimazole is due to an increase in the IL-2 available to the T cells in these cultures. Thus the in-vivo immunological effects of these drugs are likely to be complex since they may have at least two, possibly related, actions on the intrathyroidal lymphoid infiltrate, namely inhibiting oxygen radical generation and increasing IL-2 levels. PMID- 3098462 TI - The effect of oxandrolone on the growth hormone response to growth hormone releasing hormone in children with constitutional growth delay. AB - The effect of treatment with oxandrolone, an anabolic steroid, on GH response to GH-releasing hormone (GHRH) has been evaluated in children with constitutional growth delay. Five subjects, four males and one female, aged 11.0-17.1 years were given oxandrolone 0.1 mg/kg p.o. daily for 2 months, and underwent acute administration of GHRH (GRF 1-40, 1 microgram/kg i.v.) before and after withdrawal of oxandrolone therapy. GHRH administration induced a much greater GH response, evaluated either as a peak plasma GH levels or plasma GH integrated area, after than it did before oxandrolone treatment. These findings indicate that in children with constitutional growth delay oxandrolone increases the sensitivity of somatotrophs to exogenous GHRH and, likely, to the endogenously released neurohormone. PMID- 3098463 TI - Tall stature: a clinical, endocrinological and radiological study. AB - We have studied GH secretory dynamics in 38 (25 F, 13 M) children referred for investigation and treatment of tall stature (Height SD score (SDS) greater than 1.8). Five children had elevated basal GH levels (mean 20.4 mU/l) and a further four had abnormal GH responses to exogenous TRH. Two other children had paradoxical GH responses to oral glucose loading. Although one of these was receiving high dose testosterone to limit final height. All these children were pubertal and did not show concordance between peak GH concentration observed after insulin-induced hypoglycaemia and during stage IV sleep. Twenty-four hour GH profiles revealed increased GH pulse amplitude and area under the pulse during puberty. Morning GH secretion was also regularly observed and it is possible that the paradoxical responses seen by us and reported by others reflect this increased physiological secretion. Pituitary radiology revealed morphological abnormalities suggestive of microadenomata in 17 patients but these were all in late puberty and these changes may be related more to the effects of sex hormones than to somatotroph pathology. 'Abnormal' endocrinology and radiology are seen in tall children in puberty and must be interpreted with caution. PMID- 3098464 TI - Transient hypogonadotrophic hypogonadism after head trauma: effects on steroid precursors and correlation with sympathetic nervous system activity. AB - Transient hypogonadotrophic hypogonadism commonly occurs after major medical insults. Because data on testosterone precursors are sparse and because little is known about the aetiology of these changes, we studied the interactions of traumatic brain injury with gonadal steroidogenesis and with sympathetic nervous system activation. Patients were divided into two groups based upon the severity of neurological dysfunction using the Glasgow Coma Score (GCS); Group 1 less than 8, Group 2 greater than or equal to 8. Group 1 was further divided into those patients treated (Group 1b) and those not treated with dexamethasone (Group 1a). Plasma levels of testosterone, androstenedione, 17-hydroxyprogesterone, DHEA sulphate, cortisol, LH, FSH, and the catecholamines noradrenaline (NE), adrenaline (EPI) and dopamine were measured in 31 acutely brain injured men, aged 18-95, shortly after their accident and 4 days later. In all patients, NE and EPI were elevated on admission (NE: 841 +/- 105 (SEM) pg/ml; EPI: 191 +/- 32 pg/ml and there were highly significant inverse correlations between admission NE (r = 0.52, P less than 0.003) and EPI (r = 0.44, P less than 0.02) levels and day 4 testosterone concentrations. Testosterone fell 53% (P less than 0.001) in 13 Group 1a men, but only 25% (P = NS) in the less severely injured. Similar reductions occurred in cortisol and the steroid precursors. However, only testosterone, 17-hydroxyprogesterone, and DHEA sulphate levels were significantly lower than normal on day 4. LH and FSH levels were also significantly reduced from elevated admission levels. In the eight men treated with dexamethasone (8-40 mg/ml) (Group 1b), the decrease in testosterone, LH and FSH concentrations were similar to those present in Group 1a. Thus, severe traumatic brain injury leads to hypogonadotrophic hypogonadism which affects testosterone and its precursors. The magnitude of the hormonal dysfunction is dependent upon the severity of the neurological insult. Finally, the decrease in testosterone is significantly correlated with admission catecholamine levels, which may suggest a role for the sympathetic nervous system (SNS) in mediating this response in men. PMID- 3098465 TI - The assessment of diminished testicular function in boys of pubertal age. AB - Nine boys with anorchia and 9 individuals with diminished testicular function were followed between ages 10 and 18 with serial determinations of urine gonadotrophins and serum testosterone. Ten hCG stimulation tests were performed in eight of these patients. Adult levels of LH (greater than 500 mIU/h) and low measurements of serum testosterone (less than 54 ng/dl) confirmed the anorchic state. Boys with diminished testicular reserve exhibited urinary gonadotrophin changes similar to peripubertal anorchic patients but testosterone levels increased progressively with age (90-715 ng/dl). FSH attained adult castrate levels (greater than 1700 mIU/h) by age 13 in these boys and served to distinguish them from normal controls. The longitudinal assessment of basal hormone levels can separate anorchia from diminished testicular reserve in boys of pubertal age and testing with hCG is not required for evaluation. PMID- 3098466 TI - First trimester diagnosis of Pompe's disease (glycogenosis type II) with normal outcome: assay of acid alpha-glucosidase in chorionic villous biopsy using antibodies. AB - Prenatal diagnosis of glycogenosis type II was performed by direct assay of acid alpha-glucosidase (EC 3.2.1.20) in chorionic villous biopsy obtained by transcervical cannula aspiration from a pregnancy at risk in the 10th week of gestation. The exact value of the enzyme activity estimated by the use of antibody preparations for purified human liver acid alpha-glucosidase was in the heterozygous range, and so the homozygous enzyme deficiency could be excluded. The subsequent analysis of cells cultured from amniocentesis sampling in the 18th week of gestation resulted in a similar outcome. The study with antibodies showed that in 23 control chorionic villi obtained during gestational ages between 7-13 weeks, 1-15% of the total alpha-glucosidase activity at pH 4.0 were due to renal or neutral enzyme. This indicates that it may be important to employ antibodies for prenatal diagnosis using chorionic villous sampling. A healthy and unaffected boy was born. The biochemical values obtained from an umbilical blood specimen were in accordance with the results of the prenatal diagnosis. PMID- 3098467 TI - The arylsulphatases of chorionic villi: potential problems in the first-trimester diagnosis of metachromatic leucodystrophy and Maroteaux-Lamy disease. AB - Three pregnancies at risk for late infantile metachromatic leucodystrophy have been monitored using chorionic villus biopsies. In the first of these a false negative diagnosis was made following assay of arylsulphatase A in villi. Subsequent studies have shown that this error was probably due to interference from another sulphatase in the villi, although the possibility that maternal contamination was also partly responsible could not be excluded. For reliable prenatal diagnosis of metachromatic leucodystrophy using chorionic villi it is advisable that studies with the nitrocatechol substrate are carried out on fractionated homogenates, or that the natural substrate is used. Problems may also occur when chorionic villi are used for assay of arylsulphatase B for first trimester diagnosis of Maroteaux-Lamy disease. PMID- 3098468 TI - Circulating monoclonal IgM lambda cryoglobulin with collagen type I affinity in vasculitis. AB - A previously fit 66-years-old male primarily presented symptoms compatible with Henock-Schonlein's purpura, from which he seemingly recovered. Shortly hereafter he relapsed with an IgM lambda essential monoclonal cryoglobulinemia type I, presenting a systemic, necrotizing vasculitis, with low titer of circulating immune complexes and complement consumption. Glucocorticoid treatment and plasmapheresis did not prevent an ultimately lethal course. An indirect immunoperoxidase technique showed that the cryo-IgM bound to the interstitial connective tissue corresponding to the localization of collagen type I. In addition it bound to affinity purified human procollagen type I. These results indicate, that the IgM lambda of the proband was an autoantibody with collagen type I specificity. PMID- 3098469 TI - Idiotypes and autoimmunity. PMID- 3098470 TI - Regulation of the in vitro monoclonal immunoglobulin production in cultures of peripheral blood mononuclear cells and bone marrow cells from myeloma patients mediated by T cell dependent mitogens. AB - In vitro monoclonal immunoglobulin (mIg) production of cultured tumour cells- prepared from the bone marrow (BM) or from the peripheral blood (PB) of 40 multiple myeloma (MM) patients, 16 patients with monoclonal gammopathy of undetermined significance and two patients with M. Waldenstrom--was measured with an enzyme-linked immunosorbent assay (ELISA) using anti-idiotype and anti-class specific antisera. After in vitro stimulation with pokeweed mitogen (PWM) or OKT3 antibody, mIg production was regularly suppressed in BM cell cultures, whereas enhanced, unaltered or suppressed production was observed in PB cell cultures. These observations show that the expanded clone in MM can still be regulated in vitro. Separation experiments demonstrated the involvement of T cells in this in vitro system. The results could be explained by the hypothesis that activated T cells can suppress mature cells of B cell differentiation, as found in BM of the patients, but stimulate earlier B cells from the peripheral blood towards differentiation into Ig secreting cells. PMID- 3098471 TI - Differential expression and regulation of MHC products in the endocrine and exocrine cells of the human pancreas. AB - Inappropriate expression of HLA Class II (D/DR) molecules has been detected in the target cells of most autoimmune diseases including Type I (insulin-dependent) diabetes. The possibility that this phenomenon is due to the action of lymphocytes or some of their products has been investigated by analysing in vitro the modulation of HLA products in Beta cells. Monolayer cultures from 25 human pancreatic glands were supplemented with alpha-interferon (IFN), beta-IFN or gamma-IFN, interleukin 2 (IL-2) and supernatants from activated lymphocytes. In addition, lectins and a variety of other hormones, biological products and chemicals were tested. Major histocompatibility complex (MHC) expression was assessed by double immunofluorescence technique using monoclonal antibodies to non-polymorphic determinants of Class I and Class II molecules and the pancreatic cells were identified by antibodies to islet hormones and other cytoplasmic antigens. gamma-IFN and lectins produced a parallel enhancement of HLA-A,B,C expression in islet, exocrine/ductal cells and fibroblasts. HLA-D/DR was inducible in all pancreatic cell types, except endocrine islet cells which did not produce Class II molecules in response to any of the stimuli including supernatants from activated lymphocytes. Exocrine/ductal cells from glands of patients with chronic pancreatitis spontaneously expressed Class II products, but islet cells were devoid of any detectable D/DR. These data are consistent with recent observations which have indicated that in the 'diabetic' pancreas inappropriate Class II expression in the Beta cells occurs independently of the presence of lymphocytes infiltrating the islets, and make it necessary to postulate that other factors are responsible for the Class II induction in Beta cells in human Type I diabetes. PMID- 3098472 TI - Interleukin 2 enhances natural killing of varicella-zoster virus-infected targets. AB - Preincubation of peripheral blood non-adherent mononuclear cells with purified or recombinant interleukin 2 (IL-2) significantly enhanced natural killer (NK) activity against uninfected and varicella-zoster virus (VZV)-infected targets, while antibody-dependent cellular cytotoxicity (ADCC) against VZV-infected targets was not increased. Preincubation of effector cells with IL-2 had no effect on conjugate formation, but lysis of both targets was increased in single cell assays. IL-2-enhanced NK against VZV-infected targets was independent of gamma-interferon (gamma-IFN) production. PMID- 3098473 TI - The specificity of serum and local antibodies in female gonorrhoea. AB - Immunoblotting has been used to compare the specificity of serum and local IgG and IgA antibodies in 13 women with gonorrhoea and in 13 controls. The technique allowed the simultaneous detection of antibodies to the major outer membrane proteins I, II, and III, pili and lipopolysaccharide; antibodies to another antigen which is probably a 'carbohydrate' were also detected. Serum and local IgG and IgA were found to be produced to several antigens during gonococcal infections, although the quantity of antibody was greater in serum. There was little change in the specificity of serum antibodies whereas the local response to LPS and pili increased over the two week study period. Serum antibody to LPS was more often IgG than IgA. Sera contained antibodies to 'carbohydrate', pili and lipopolysaccharide (LPS) whilst the local response was largely to the latter two antigens. Antibody to the outer membrane proteins was rarely detected. Control sera, but not vaginal washings, contained IgG and IgA to the major antigens but the staining of the immunoblots was less intense than those from patient's sera suggesting quantitative differences. PMID- 3098474 TI - Detection and quantification of circulating antigen in schistosomiasis by a monoclonal antibody. I. Specificity analysis of a monoclonal antibody with immunodiagnostic capacity. AB - Monoclonal antibodies were obtained after immunization of mice with Schistosoma mansoni excretory/secretory antigen, previously shown to contain the circulating cathodic (M) antigen. Among these, the 40:B1 monoclonal antibody proved to be specific for the schistosome genus and to detect only adult worm-derived antigens as shown both by immunoprecipitation and with a two-site immunoradiometric assay using the monoclonal as both the solid-phase and the labelled antibody. The two site immunoradiometric assay allows a sensitive measurement (detection limit: 5 ng) of circulating schistosome antigen in blood and in urine from patients with schistosomiasis. The amount of circulating schistosome M antigen is correlated with schistosome egg excretion in stool. PMID- 3098475 TI - Detection and quantification of circulating antigen in schistosomiasis by monoclonal antibody. II. The quantification of circulating antigens in human schistosomiasis mansoni and haematobium: relationship to intensity of infection and disease status. AB - Circulating cathodic and circulating anodic antigens were quantified in sera of patients infected with S. mansoni, S. haematobium or both parasites. A monoclonal antibody and a polyclonal antiserum were applied in precipitation and solid phase immunosorbent techniques using radio- and enzyme-labelled antibody as a tracer to detect the cathodic and anodic antigen respectively. The results show that circulating cathodic antigen can frequently be detected in an immunoprecipitation or an immunoradiometric assay in serum of infected patients. The serum concentration of this antigen was found to be significantly correlated to the number of S. mansoni worms and to be higher in patients with the hepatosplenic form of the disease than in those without such complications. Examining paired serum samples before and after specific treatment the determination of this antigen by monoclonal antibody reliably indicated efficacy of chemotherapy in patients having received different forms of treatment. PMID- 3098476 TI - Protection against experimental Schistosoma mansoni schistosomiasis achieved by immunization with schistosomula released products antigens (SRP-A): role of IgE antibodies. AB - Schistosomula-released products (SRP-A) have been shown to induce preferentially a significant IgE response against Schistosoma mansoni schistosomula when injected into rats, in the absence of adjuvant. The present work provides additional evidence of the in vivo relevance of the anti-SRP-A target antigens. Two strains of rat (Brown Norway and Fischer) were immunized with SRP-A and infected percutaneously. A significant level of protection (up to 83% reduction in worm burden) was observed. Passive transfer experiments carried out with anti SRP-A or IgE-depleted anti-SRP-A sera suggested the preponderant role of antibodies and particularly of IgE in the protective immunity developed by Fischer rats. Platelets and macrophages recovered from such immunized rats had surface IgE as demonstrated by immunofluorescence analysis with FITC anti-IgE, and have been shown to be directly cytotoxic for schistosomula. The chemiluminescence observed when the macrophages were incubated with anti-IgE suggested the presence of IgE on the surface of these cells. PMID- 3098477 TI - Glucocorticoid enhances gamma interferon effects on human monocyte antigen expression and ADCC. AB - The expression of HLA-DR antigen by highly enriched human monocytes cultured in serum free medium was found to be markedly elevated by human recombinant gamma interferon (IFN-gamma). This effect was maximal after 48 h in culture with 300 mu/ml IFN-gamma. Class I MHC antigen also increased with IFN-gamma treatment. By contrast, binding of a myeloid-specific monoclonal antibody, AML-2-23, was dramatically decreased by IFN-gamma. The augmentation of MHC antigens was not ablated by an immunosuppressive concentration (2 X 10(-7) M) of the glucocorticoid dexamethasone (DEX). In fact, both the enhancement of Class I and Class II MHC antigen expression and the suppression of AML-2-23 antigen by IFN gamma were often more profound in the presence of DEX. IFN-gamma treatment also resulted in elevated monocyte effector function, as measured by antibody dependent cellular cytotoxicity (ADCC). This functional activation was not inhibited by DEX. On the contrary, DEX slightly augmented IFN-gamma effects on ADCC. This contrasts with other reports that glucocorticoids inhibit monocyte responsiveness to lymphokines, and suggests that the interplay between lymphokines and the glucocorticoid hormones may be more complex than previously thought. PMID- 3098478 TI - A longitudinal study of gamma-interferon production by peripheral blood mononuclear cells from breast- and bottle-fed infants. AB - Production of gamma-interferon (gamma-IFN) in vitro by peripheral blood mononuclear cells (PBMC) from 15 breast-fed and 15 bottle-fed infants has been studied from birth to 9 months of age and compared with production by adult cells. Using a Terasaki plate microculture system with serum-free medium, PBMC were stimulated with staphylococcal enterotoxin A (SEA) and gamma-IFN production was assessed by an immunoradiometric assay. Cord blood mononuclear cells (CBMC) and PBMC from all infants secreted large quantities of gamma-IFN. The levels secreted did not change significantly with age over the 9 months of the study, nor did they differ from the levels secreted by adult cells. Cells from the bottle-fed infants secreted slightly more gamma-IFN than cells from breast-fed infants, but this difference was not significant. These results indicate that the potential for PBMC to secrete gamma-IFN in vitro is fully developed at birth in full-term infants and cannot therefore be further influenced by subsequent breast or bottle-feeding. In addition, the greater susceptibility of infants than adults to certain bacterial and viral infections cannot be attributed to a deficiency in the potential of infant cells to secrete gamma-IFN in vitro. PMID- 3098479 TI - Dipyridamol inhibits activation of human T lymphocytes in vitro. AB - The effect of dipyridamol on T-lymphocyte activation was investigated. The drug did not have an irreversible toxic effect on T lymphocytes. Dipyridamol inhibited both PHA- and mumps-stimulated proliferation and the proliferative response in mixed lymphocyte cultures. The drug inhibited PHA-stimulated proliferation independent of the time when it was added during the culture period. The PHA stimulated expression of interleukin-2 (IL-2) receptors and IL-2 production (at least for low concentrations) was not inhibited. Dipyridamol inhibited IL-2 dependent growth of T cell lines. The drug caused no inhibition when present only during antigenic pulsing. PMID- 3098480 TI - Characterization of immunoglobulin A kappa autoantibodies to human lactate dehydrogenase isoenzyme-3. AB - We have purified with a cumulative recovery of 48% from the serum of a patient the immunoglobulin A kappa subunit of the lactate dehydrogenase-immunoglobulin A kappa (LD-IgA kappa) complex. It appears that the pI range of the complex is 5.4 5.8. The Ig part of the complex showed a monoclonal character, and the complex exhibited a 1:2 molar ratio of the Ig to the LD isoenzyme. From reconstitution experiments by two different methods we concluded that LD-3 is essential for restoring the original complex. Additional studies showed a recombination of the IgA kappa with both autologous and homologous LD-3, and a binding of LD-3 at the Fab region of the Ig. The estimated value of the affinity constant (Keq) was 2.1 X 10(9) liters/mol. Analysis of the specific LD-3-binding IgA kappa concentrations in the sera of five cases revealed a broad range of the individual immune response. Our first quantitative data on the lymphocyte subpopulations revealed a significantly increased OKT4/OKT8 ratio due to a reduction in the absolute number of T suppressor cells. PMID- 3098481 TI - Arachidonic acid metabolism is altered in sarcoid alveolar macrophages. AB - Macrophages produce various arachidonic acid (AA) metabolites which may either enhance or suppress inflammatory processes. We investigated AA metabolite production by alveolar macrophages (AMs) from 11 patients with pulmonary sarcoidosis and 9 normal volunteers. We assessed the production of both cyclooxygenase products (prostaglandin (PG) E2, thromboxane B2 (TXB2), PGF2 alpha, and 6-keto-PGF1 alpha) and lipoxygenase products (leukotrienes (LT) and hydroxyeicosatetraenoic acids (HETEs] in AM cultures. We found that sarcoid AMs produced less PGE2, TXB2, 6-keto-PGF1 alpha, and HETEs in both the unstimulated and the calcium ionophore-stimulated states compared with normal AMs. Sarcoid AMs also produced less PGF2 alpha and LTs in the unstimulated state after 1 hr of incubation, but following calcium ionophore stimulation, these differences did not achieve statistical significance. We conclude that sarcoid AMs have a reduced capacity to produce AA metabolites compared with that of normal AMs. PMID- 3098482 TI - Association of lupus anticoagulant with antibody against phosphatidylserine. AB - Lupus anticoagulant (LAC) is an antiphospholipid autoantibody identified by prolongation of in vitro phospholipid-dependent coagulation tests. Its presence is associated with thromboembolic disease and recurrent pregnancy loss in patients with or without clinical autoimmune disease. The purpose of this study was to identify the specific phospholipid(s) against which LAC is directed. The sera of 15 patients with LAC and of 41 LAC-negative controls were evaluated. Specific phospholipids were used to inhibit IgG binding in a partial thromboplastin ELISA, and serologic reactivity was measured with ELISAs which used specific phospholipids in the solid phase. Both phosphatidylserine and cardiolipin significantly inhibited IgG binding in the partial thromboplastin ELISA (76 and 75%, respectively); however, the serum of one patient who was strongly positive for LAC in coagulation assays was not inhibited by cardiolipin. In the specific phospholipid ELISAs, LAC-positive sera contained IgG (15 of 15 sera) and frequently IgM (9 of 15 sera; 60%) to phosphatidylserine. Most LAC positive sera also contained IgG antibodies against other phospholipids: cardiolipin (10 of 11 sera; 91%), phosphatidylcholine (1 of 15 sera; 7%), phosphatidylethanolamine (12 of 15 sera; 80%), phosphatidylglycerol (12 of 15 sera; 80%), and phosphatidylinositol (10 of 15 sera; 67%). None of the LAC negative controls had measurable IgG against any of these phospholipids. We conclude that LAC-positive sera contain antibody specificities against multiple phospholipids; however, anticoagulant activity is always associated with the presence of antibodies against phosphatidylserine. PMID- 3098483 TI - Factor VIII complex in progressive systemic sclerosis. AB - Factor VIII complex and its related activities (Coagulant, Antigen and Ristocetin Cofactor) have been investigated in 23 patients with Progressive Systemic Sclerosis (PSS) divided into two groups: acrosclerosis and diffuse sclerosis. All Factor VIII-related activities were higher in PSS patients than in normal subjects. No difference in F. VIII-related Antigen (F. VIIIR:Ag), F. VIII-related Ristocetin Cofactor (F. VIIIR:Co) and F. VIII Coagulant activity (F. VIII:C) was found comparing the patient groups. F. VIII:C was increased significantly less than F. VIIIR:Ag and F. VIIIR:Co in both patient groups. Some hypotheses about the pathogenesis of this increase are discussed. PMID- 3098484 TI - The acute phase response in scleroderma. Differing responses to intravenous PGE1. AB - A defective acute phase response of scleroderma patients following intravenous PGE1 infusion has been reported. Serum C-reactive protein levels in scleroderma patients before and after a seventy-two hour infusion of either PGE1 or placebo were measured in the present study. The mean baseline serum CRP level in scleroderma patients was significantly greater than in normal controls (12 +/- 9.0 mcg/ml vs 1.4 +/- 1.7 mcg/ml) (p less than 0.001). Before the intravenous infusion, the PGE1-treated and placebo-treated groups had mean serum CRP concentrations of 14 +/- 9 and 10 +/- 9 mcg/ml, respectively. After the three-day infusion, these values were 109 +/- 75 and 11 +/- 10 mcg/ml (p less than 0.01). Scleroderma patients appeared to have two types of response to PGE1. Three patients had large increases (mean = 167 +/- 32 mcg/ml) and three had smaller increases (mean = 22 +/- 17) (p less than 0.005). The patients with greater increases had disease of shorter duration and greater cutaneous involvement. Overall, the acute phase response appears to be intact in scleroderma patients, but may differ in degree. PMID- 3098485 TI - Gold pneumonitis. A case report with electronmicroscopy and electron probe analysis. AB - A case of classical RA developed severe interstitial pulmonary disease and respiratory failure while on chrysotherapy. A high concentration of gold was found in lung tissue. Electron microscopic and electron probe examinations confirmed the presence of gold in the interstitial and intra-alveolar macrophages. The clinical course and possible pathogenic mechanism were discussed. PMID- 3098487 TI - [Adult type galactosialidosis--alcohol and myoclonus]. PMID- 3098486 TI - Total parenteral nutrition in mice bearing a metastatic carcinoma: tumor growth, metastasis and immunologic parameters. AB - The role of dietary manipulation of tumor growth, metastasis and immunologic parameters was studied in mice bearing Lewis lung carcinoma. Fourteen days following subcutaneous tumor implant, groups with tumor and their non-tumor bearing counterparts were assigned to one of the following feeding protocols: total parenteral nutrition (TPN), per oral (PO) intake of the parenteral diet, an oral casein diet (CAS), or electrolyte infusion plus the casein diet (ELECT). Intakes of energy and nitrogen were similar among all groups. Mice were killed 12 days later and peritoneal macrophages were tested for phagocytic activity. Tumor growth and metastasis were decreased from both infusion regimens with minimal loss of body weight as compared with casein fed mice. PO mice also showed lower tumor weight but metastasis was as great as in the casein group. Non-tumor bearing infused mice showed depressed thymic weight, but thymic weight was not further reduced in tumor-bearing infused mice. PO feeding afforded no such protection in the presence of the carcinoma. Splenomegaly was observed in tumor bearing mice on all regimens, but mice maintained on the parenteral diet demonstrated the largest proportion of macrophages containing nuclear debris. Analysis of free macrophages indicated no effect of diet regimen on non-immune phagocytic activity in both tumor-free and tumor-bearing mice. Possible alteration of splenic macrophage intracellular digestive capacity or phagocytic activity was suggested as a result of TPN. PMID- 3098488 TI - Experience with gliomas in patients presenting with a chronic seizure disorder. PMID- 3098489 TI - An evaluation of the in utero neurosurgical treatment of ventriculomegaly. AB - Clinical results for in utero treatment of ventriculomegaly are not impressive; results may improve, however, with new techniques and more experience. Nonetheless, even in the best of hands, it is not always possible to identify associated and sometimes fatal congenital abnormalities on high resolution obstetric ultrasonograms, and not enough is known of the natural history of CNS congenital disease, in particular of ventriculomegaly, to select the appropriate fetus for in utero treatment. Results of animal studies are encouraging, but more work is needed to define the pathophysiology, knowledge of which might allow selection of the appropriate fetus and treatment modality. PMID- 3098490 TI - Unique pattern of interleukin 2 receptor expression by lymphocytes in response to anti-Leu 4 monoclonal antibody: relationship to monocyte accessory cell function. AB - The relationship of early interleukin 2 receptor (IL2R) expression to subsequent DNA synthesis by mitogen-stimulated human mononuclear cells (MC) was studied. For serial dilutions of a given mitogen, the percentage of lymphocytes expressing IL2R after 1 day of culture was plotted vs 3H-thymidine incorporation on day 3, and the IL2R value associated with a proliferative response of 50,000 counts per minute (IL2R-50K) determined. A mean IL2R-50K value of 7 characterized PHA, Con A, and OKT3 responses, while a higher mean value of 29 characterized anti-Leu 4(L4) responses. As tested in OKT3 and L4 systems, the addition of exogenous IL2 did not alter IL2R-50K values. Because both OKT3 and L4 recognize the lymphocyte CD3 antigen but react with different monocyte Fc receptors, the role of monocytes in producing elevated L4 IL2R-50K values was explored. MC from healthy L4 nonresponders (NR), induced to proliferate with L4 in the presence of responder (R) monocytes, also yielded an elevated mean IL2R-50K value of 31. In contrast, direct stimulation of R-MC, NR-MC, or NR-MC plus R monocytes by L4-coated sepharose beads produced lower mean IL2R-50K values of 12 or 13. Two-color cytofluorescence studies measuring IL2R and transferrin receptor (TR) on day 2 of culture revealed that most of the increase in IL2R+ cells in response to L4 was attributable to IL2R+TR-cells. These findings suggest that crosslinking of lymphocyte-bound soluble L4 by R monocytes leads to a uniquely elevated pattern of IL2R expression involving a disproportionate increase in the level of IL2R+TR cells. PMID- 3098491 TI - The contribution of molecular biology in the diagnosis of human lymphomas. AB - The relationship between T cell receptor (TCR) beta and gene immunoglobulin heavy chain locus was investigated in 25 cases of unselected human lymphomas as well as in normal and non-neoplastic lymphoid tissues. Hybridizing our blots with Jurkat 2, a clone specific for the beta chain gene of TCR, did not demonstrate extra bands in non-neoplastic tissues composed of 50-95% T-cells. On the contrary, rearranged bands were detected in six out of six cases of T-cell lymphomas. No TCR beta gene rearrangements were detected in 11 B-cell lymphomas, which in turn presented modification of the immunoglobulin heavy chain gene germline configuration. Our results suggest that TCR beta chain gene rearrangements are a good marker for human T-cell neoplasias in humans and complement the analysis with immunoglobulin genes probes. Eighth samples were devoid of any rearrangements: this group comprises cases of Hodgkin's disease T-lymphoblastic lymphomas in clinical remission and malignancies of unknown origin, as discussed in the text. We conclude that the analysis using DNA probes specific for TCR beta and IgH genes can be of aid to the pathologist in the diagnosis and classification of human lymphomas. PMID- 3098492 TI - The value of non-staging skeletal scintigraphy in breast cancer. AB - A series of 315 patients with histologically proven breast cancer had skeletal scintigraphy performed for defined reasons other than initial staging. Of these, 173 (55%) were found to be abnormal. The yield of abnormalities was highest (83%) in patients with bone pain or tenderness and radiographic evidence of metastases: 38% in those with bone pain or tenderness alone, 37% in asymptomatic patients with local or regional recurrence and 54% in those with non-bony metastases. The overall actuarial survival over a maximum follow-up of 9 years was significantly worse for those with abnormal scintigraphy. Non-staging skeletal scintigraphy is useful in detecting asymptomatic bone metastases at the time of local or regional recurrence or in the presence of non-bony metastases. PMID- 3098493 TI - Is there an optimal dose and formulation of aspirin to prevent arterial thrombo embolism in man? PMID- 3098494 TI - [Oral disodium cromoglycate: alternative therapy of ulcerative rectocolitis]. PMID- 3098495 TI - Adenylic nucleotides and energy charge during the embryonic development of Bufo arenarum. AB - The contents of ATP, ADP and AMP were determined by HPLC and adenylic energy charge (AEC) was estimated during different stages of the embryonic development of Bufo arenarum up to the tailbud stage. All the developmental stages studied showed a high ATP content (about 1.04-1.48 nmol/emb.). The concentration of ADP was low (0.025-0.041 nmol/emb.) but rose slightly at the neural tube stage. AMP was undetectable before the tailbud stage. AEC values were almost constant (about 0.987-0.992) throughout the period studied. Only a fall at the tailbud stage could be detected which can be related to this more advanced cellular differentiation stage. PMID- 3098496 TI - Distribution of ventilation and perfusion: a teaching model. AB - Models can be used as teaching tools to study complex phenomena. This model uses simplifications of blood gas subroutines to provide fast execution of the effect of the distribution of ventilation and blood flow in the lung on arterial blood gases. Assumptions are made that introduce only small errors but that avoid the use of iterations which would slow down execution. The use of Turbo-Pascal as the programming language allows for not only speed in development and execution but also portability to a variety of computers including CP/M systems and IBM-PCs. PMID- 3098497 TI - DRG's, myths and facts. PMID- 3098498 TI - Recovery of fertility after use of the levonorgestrel 20 mcg/d or Copper T 380 Ag intrauterine device. AB - Following use of either the Levonorgestrel 20 mcg/day or the TCu 380 Ag IUD in a randomized comparative study, 110 women stopped contracepting to have planned pregnancies. Pregnancy rates and recovery of fertility have been assessed. Age at acceptance, duration of use, parity and intervals between last pregnancy and IUD insertion or removal were similar for both groups. Life table pregnancy rates at one year were higher than 90 per cent for both device groups; but because some women quickly changed their minds or had been at risk of pregnancy only a short time before the analysis date, only 60.9 percent had actually become pregnant. Median time to planned pregnancy was 3 months for the TCu 380 Ag group and 4 months for the Levonorgestrel 20 group. Neither duration of use nor age at insertion or age at termination affected the pregnancy rates significantly. PMID- 3098500 TI - Small-pool high-yield factor VIII production. AB - Hemophilia care depends on several factors for the production of purified FVIII: plasma procurement, plasma logistics, production method, and efficacy. The latter two are restrictive factors, both for the supply and the safety of FVIII preparations. Conventional production methodology unavoidably recovers only 10 to 20% of usable protein, therefore requiring large pools of source plasma. Related to pool size is the transmission of diseases, which poses unnecessary risks for patients. The development of new technologies to better recover FVIII allows reduction of the pool size: crush-thaw, controlled pore-glass chromatography, and heparin double-cold precipitation techniques. This review will reflect on current production methods, pool size concept, small-pool approaches in FVIII production, and future developments. PMID- 3098501 TI - Carbon dioxide production during mechanical ventilation. AB - Because of large stores of CO2 in different body tissues, metabolic change cannot be detected by measuring gas exchange until the CO2 stores have adapted to the new situation. Similarly, changes in the CO2 stores not due to metabolic alterations, may lead to error in gas exchange measurements. We studied CO2 production (VCO2) and oxygen consumption (VO2) in mechanically ventilated ICU patients, where CO2 stores were altered by: a) changing minute ventilation by 15%, b) reducing body temperature, and c) changing the level of sedation. Expired gases went through a mixing chamber and were analyzed continuously by a mass spectrometer. Signals from this instrument, together with gas-volume signals from the ventilator, were fed to a computer for calculation of VO2 and VCO2. Twenty to 120 min were required to reach a stable level, depending on the patient's size and circulatory response. Similar results were obtained by computer simulation using a five-compartment model of CO2 stores. These experiments indicate that measuring VO2 (for calculation of metabolic respiratory quotient [RQ]) in ventilated patients should occur after the patients maintain a 60-min period of stable body temperature and awareness. Ventilatory variables should not be changed substantially during the 90-min period before gas sampling. Cardiac output and muscle blood flow should not have changed 2 to 3 h before measuring RQ. If muscle blood flow is low, the stable periods for body temperature and ventilatory variables should be increased. PMID- 3098499 TI - Effect of oral contraceptive on liver function tests of women with schistosomiasis in the Philippines. AB - A prospective study was undertaken to determine the effect on liver function tests of a combined oral contraceptive containing norethisterone 1 mg and mestranol 0.05 mg, in women with schistosomiasis japonica in Leyte, Philippines. Women who volunteered and met the standard criteria for oral contraception, with and without infection, were followed for six months of pill intake. Concurrently, non-pill users, both infected and uninfected, were similarly followed. Baseline and six-month liver function tests were compared. Of the 466 subjects admitted in the study, 383 completed six months, and 83 discontinued. At the start of the study, there were no significant differences among the four groups in liver function tests except that the infected women had a higher total protein and alkaline phosphatase, and lower alanine aminotransferase levels. After six months, the only statistically significant finding was a lesser decrease in total protein among the infected pill users compared to the uninfected pill users. This finding was not clinically significant since there was no associated clinical complications; there were fewer number of subjects with abnormal values at the sixth month; and the mean values of this variable remained within normal limits. Our findings show that the use of low dose progestin and estrogen oral contraceptive in the presence of mild schistosomiasis japonica infection does not appear to have adverse effect on liver function tests of young women after six months of contraceptive use. PMID- 3098502 TI - Eye infections caused by respiratory pathogens in mechanically ventilated patients. PMID- 3098503 TI - The central metabolic pathways of Escherichia coli: relationship between flux and control at a branch point, efficiency of conversion to biomass, and excretion of acetate. PMID- 3098504 TI - Lymphokine regulation of murine IgE production. PMID- 3098505 TI - Molecular genetics of human B-cell neoplasia. PMID- 3098506 TI - Expression of c-myc and c-fos during phorbol ester induced differentiation of B type chronic lymphocytic leukemia cells. PMID- 3098507 TI - Experience in surgical treatment of intracranial aneurysms. Report of 520 patients. PMID- 3098508 TI - Cellular elements in giant cell tumor of bone. Feulgen-DNA quantitation, 3H-TdR incorporation and ultrastructure observation. PMID- 3098509 TI - Relationship between breast parenchymal pattern and breast cancer incidence. PMID- 3098511 TI - Schistosomiasis control in hilly regions of Fujian Province. PMID- 3098510 TI - Studies on leishmaniasis in China. Historical background, epidemiology, clinical aspects, legislature and control program. PMID- 3098512 TI - Radix Tripterygium Wilfordii Hook F in rheumatoid arthritis, ankylosing spondylitis and juvenile rheumatoid arthritis. PMID- 3098513 TI - T lymphocyte subpopulations in chronic renal failure. PMID- 3098514 TI - Treatment of experimental respiratory distress syndrome with dexamethasone, scopolamine and anisodamine in dogs. PMID- 3098515 TI - Gray scale ultrasonic manifestations of breast tumor. An analysis of 71 cases. PMID- 3098517 TI - Combined horizontal and vertical retraction syndrome. A case report. PMID- 3098516 TI - Neurotropin immunostimulating action on immunocompetent cells. PMID- 3098518 TI - Reevaluation of treatment of brain abscess by puncture. PMID- 3098519 TI - Breast cancer in Beijing. PMID- 3098520 TI - [Treatment of membranous cataract with YAG laser]. PMID- 3098521 TI - [Energy dispersive X-ray analysis of senile cataract]. PMID- 3098522 TI - [Scanning electron microscopy of normal and senile cataractous lenses]. PMID- 3098523 TI - [Lensectomy and vitrectomy. Analysis of 320 cases]. PMID- 3098524 TI - [Fibrovascular proliferation at the pars plana incision after vitreous surgery]. PMID- 3098525 TI - [Long-term follow-up studies on the modes of surgical treatment of congenital cataract]. PMID- 3098526 TI - [Diabetic ocular lesions and hypomagnesemia]. PMID- 3098527 TI - [Clinico-pathological analysis of optic nerve gliomas]. PMID- 3098528 TI - [Immunological analysis of 104 cases of endogenous uveitis]. PMID- 3098529 TI - [Telescope magnifiers for distant vision]. PMID- 3098530 TI - [Evaluation of trachoma treatment by the cytological examination of scrapings]. PMID- 3098531 TI - [Lenses of experimental dogs exposed to nuclear explosion]. PMID- 3098532 TI - [Blindness survey in Hunan Province, China]. PMID- 3098533 TI - [Clinical significance of the assay of factor VIII--related antigen in 60 cases of chronic cor pulmonale]. PMID- 3098535 TI - An interview with Dr. Ron Jordan. PMID- 3098534 TI - Chronic recurrent pancreatitis secondary to a submucosal ampullary tumor in a patient with neurofibromatosis. AB - We report a 45-year-old nonalcoholic patient with Von Recklinghausen's disease and chronic recurrent pancreatitis. On endoscopy, a benign-appearing submucosal tumor surrounded the papilla of Vater. Cannulation of the pancreatic duct showed a dilated ductal system with subsequent delayed drainage. Endoscopic manometry revealed elevated sphincter of Oddi pressures. Endoscopic sphincterotomy resulted in immediate normal drainage of the pancreatic duct and in subsequent clinical improvement. PMID- 3098536 TI - Dental hygiene--the vital issues. PMID- 3098537 TI - Dentistry--under legal attack. PMID- 3098538 TI - Computers--most asked questions. PMID- 3098539 TI - Communication--your way with words. PMID- 3098540 TI - Disposition of chloramphenicol in young rhesus monkeys with protein-energy malnutrition. AB - The disposition of chloramphenicol was studied in young rhesus monkeys at three levels of nutrition: control, protein-energy deficiency, and following nutritional rehabilitation. During the malnutrition phase, the plasma elimination half-life was prolonged and the plasma clearance was reduced. Simultaneously there was a decrease in the activity of chloramphenicol-specific UDP-glucuronyl transferase. These changes were reversible following nutritional rehabilitation. PMID- 3098541 TI - Mupirocin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. AB - Mupirocin (pseudomonic acid A) is a novel topical antibacterial agent which inhibits bacterial protein and RNA synthesis. It has excellent in vitro activity against staphylococci and most streptococci, but has less activity against other Gram-positive and most Gram-negative bacteria. Its rapid systemic metabolism means it will only be used topically which, combined with its novel chemical structure, should make cross-resistance less likely to occur than with other currently available topical antibacterial agents. Mupirocin 2% ointment administered 2 or 3 times daily has shown excellent efficacy in both primary and secondary superficial skin infections, usually with at least 80% of patients being clinically cured or markedly improved, and over 90% eradication of the bacterial pathogen involved. Efficacy in impetigo and, to a somewhat lesser extent, infected wounds has been particularly convincingly demonstrated, while in other secondary skin infections the clinical response seen with mupirocin was often similar to the high success rate of vehicle alone. Limited evidence suggests that mupirocin may be as effective as chlortetracycline, fusidic acid, neomycin and other antibacterial agents, but more controlled, comparative studies are needed. The evidence of efficacy against nasal carriage of Staphylococcus aureus, including methicillin-resistant forms, is encouraging and currently work is being undertaken to improve the acceptability of the vehicle for this use. Side effects are limited to local reactions (in less than 3% of patients) and are no more frequent than observed with the vehicle alone. Thus, mupirocin appears to be a useful addition to the agents available for the treatment of superficial primary skin infections, such as impetigo, although its precise place in therapy remains to be established. PMID- 3098542 TI - The polyol pathway in retinal microangiopathy. AB - Two structurally unrelated aldose reductase inhibitors (sorbinil and tolrestat) were used for assessing the possible role of aldose reductase in the thickening of retinal capillary basement membranes of rats. Rats were fed either a normal diet, a 50% galactose diet, or a 50% galactose diet with the addition of an aldose reductase inhibitor. Micrographs of capillaries in the outer plexiform layer of the retina were analysed. This showed that the basement membrane thickening and the ultrastructural changes in the retinal capillaries that were induced by the galactose diet were inhibited by the addition of an aldose reductase inhibitor. Thickening of the basement membrane may be related to other tissue lesions in diabetic retinopathy. Therefore, its prevention might have a favourable influence on other aspects of this retinopathy. PMID- 3098543 TI - Aldose reductase inhibitors in clinical practice. Preliminary studies on diabetic neuropathy and retinopathy. AB - Extensive animal data now exist to indicate potential benefit of sorbinil in the treatment of the major complications of diabetes mellitus. A clinical programme has been constructed to explore this therapeutic potential and encouraging evidence of drug effect has already been observed in patients with neuropathy and retinopathy. Two small preliminary studies in patients with painful neuropathy have shown that clinically significant reduction of pain was more frequently achieved with sorbinil than with placebo. A 6-month study of patients with retinopathy, using vitreous fluorophotometry as the criterion of retinal damage, showed significant (p = 0.03) benefit for the sorbinil group compared with the placebo group. Drug evaluation in these areas is complex and difficult but it is anticipated that the accumulation of additional data will further substantiate the efficacy suggested by these early findings. The only clinically important adverse effect of sorbinil is the hypersensitivity reaction. This usually occurs during the initial weeks of therapy and is similar to that seen with phenytoin. The long term use of sorbinil is without significant adverse effects. PMID- 3098545 TI - Organochlorine residues in River Po sediment: testing the equilibrium condition with fish. AB - Organochlorine residues have been determined in sediment samples collected in the River Po, during 1980-1982 at five sampling stations. Significant higher levels have been observed in a deposition area after the confluence of a very polluted tributary. No significant differences could be observed with respect to the sampling period. Residue concentrations in sediment were correlated with the organic matter content. By using soil partition coefficients and bioconcentration factors in fish, pesticide and PCB concentrations in fish have been calculated from sediment values and compared with measured values from a previous investigation. Tentatively a quality criterion for PCB in sediment is proposed. PMID- 3098544 TI - Aldose reductase inhibitors and late complications of diabetes. AB - Neuropathy and retinopathy are two potentially serious late complications of diabetes. There is accumulating evidence that the development of these conditions is closely related to increased activity of the polyol pathway, which occurs in certain tissues as a consequence of long term hyperglycaemia. Symptomatic diabetic neuropathy may appear as one of many forms and is frequently accompanied by pain. Diabetic retinopathy is a progressive degeneration of the retina that represents one of the major causes of blindness in the developed world. A good prognosis for either of these conditions is believed to rely on early diagnosis and optimisation of glycaemic control as they become less reversible with progression of cellular damage. A new approach to the treatment of these and other late complications of diabetes may be offered by recently developed drugs, such as sorbinil, that inhibit the enzyme aldose reductase. In various animal models of late complications of diabetes sorbinil and other aldose reductase inhibitors have been shown to reverse some of the biochemical and physiological changes believed to underlie these complications. These include prevention or reversal of the accumulation of sorbitol and depletion of myo-inositol in nerve, lens and renal glomeruli. Sorbinil also counteracts the slowing of nerve conduction velocities, reverses the structural changes of Sipple stages I and II cataracts and prevents proteinuria in diabetic rats. Orally administered sorbinil is absorbed rapidly and reaches steady state plasma concentrations after 6 to 10 days' administration. Its elimination half-life is long (38-52 hours) and much greater than that of another aldose reductase inhibitor, tolrestat (10-12 hours). Within the dose range 50-250 mg about one-third of administered sorbinil appears in the urine as unchanged drug. In the small number of clinical studies of diabetic patients with neuropathies sorbinil has demonstrated limited therapeutic effects. There is now a requirement for studies of its prophylactic use and its therapeutic use in patients with diabetic neuropathy in the early stages of development. PMID- 3098546 TI - Relationships of quantitative structure-activity to comparative toxicity of selected phenols in the Pimephales promelas and Tetrahymena pyriformis test systems. AB - The relative toxic response of 27 selected phenols in the 96-hr acute flowthrough Pimephales promelas (fathead minnow) and the 48- to 60-hr chronic static Tetrahymena pyriformis (ciliate protozoan) test systems was evaluated. Log Kow dependent linear regression analyses revealed that the data from each test system consisted of two linear equations. The less toxic chemicals form a relationship which models polar narcosis; these chemicals are slightly more active than the baseline toxicity of nonionic narcotic chemicals. The more toxic chemicals form a relationship which models uncoupling of oxidative phosphorylation. Regression analysis of fathead minnow toxicity (log LC50 (mol/liter] vs Tetrahymena toxicity (log BR (mmol/liter] showed good correlation between the two systems. An exception appears to be 4-nitrophenol, which is more active in the Tetrahymena system than in the fathead minnow and lies outside the 95% confidence interval. Reanalysis following deletion of 4-nitrophenol results in the equation log LC50 = -0.9192 (log BR) -3.5035; n = 26, r2 = 0.887. PMID- 3098547 TI - Reevaluation of immunoreactive gonadotropin-releasing hormone (GnRH) levels in general circulation in women: changes in levels and episodic patterns before, during and after gonadotropin surges. AB - In order to reevaluate the earlier varying data regarding circulatory gonadotropin-releasing hormone (GnRH), we assayed extracted GnRH from the plasma frequently collected at mid-cycle in 11 women. For the analysis of episodic GnRH patterns and basal levels, blood samples were obtained at 6 h intervals for 72 h and at 15 min intervals for 2 h every 12 h throughout the experimental period. All blood samples were assayed for GnRH and selected samples for LH, FSH, estradiol and progesterone. For GnRH assay, 5 or 6 ml of blood was mixed with 60 mg of ethylenediaminetetraacetic acid, disodium salt, and 3 mg of phenylmethylsulfonyl floride immediately after blood collection. These enzyme inhibitors prevented the destruction of GnRH in the blood at room temperature for at least 4 h. Plasma GnRH was extracted through several steps including florisil absorption, acidic extraction and washing with organic solvent. Nonspecific immunoreactivity in the plasma was markedly decreased through this extraction process. Our assay values (approximate range, 0.1-2.0 pg/ml) of plasma GnRH in normal women corresponded to the low range of those obtained by others who used the alcohol extraction method. The basal levels of GnRH did not change significantly throughout 3 different periods, i.e., before, during and after the LH surges, and fluctuated between a small range of 0.11 and 1.44 pg/ml. Although the peak levels of GnRH observed in its episodic patterns did not change between the periods before and during the LH surges, they decreased significantly after the LH surge compared with those seen during the LH surges (0.93 +/- 0.07 vs 1.17 +/- 0.09 pg/ml, p less than 0.05). The present data demonstrate that immunoreactive GnRH in the extracted peripheral plasma does not change significantly in its mean, basal and peak levels during the periovulatory period except for a minor but significant decrease in the peak levels shortly after an LH surge. PMID- 3098548 TI - Modulation of testicular receptors for LH, FSH and prolactin by the administration of ovine prolactin in mature rat. AB - To elucidate the role of prolactin on testicular function, we treated mature rats with ovine prolactin (oPRL) and investigated the dose and time-dependent changes in testicular LH, FSH and prolactin receptors as well as in serum gonadotropin and steroid levels. Twelve week-old rats were injected sc with a single dose of various amounts of oPRL (0.2, 1 and 5 IU) and killed on the first, second and third days after the treatment. Testicular LH receptor decreased to 59% of the control level as a function of time while prolactin receptor increased to 244% maximally of the control level on the second day. In contrast, FSH receptor changed in a different fashion. Smaller amounts of oPRL (0.2 and 1 IU) raised the receptor level to 193% of the control level on the first day whereas a larger amount (5 IU) did not change the receptor, which tended to remain in a low level throughout the experimental period. The serum FSH level significantly increased in every group on the second day, then returned to the control range by the third day. On the other hand, the serum testosterone level changed in a characteristic manner, decreased significantly in every group on the first day though not in a dose-dependent fashion, returned to normal on the second day and significantly increased in the 0.2 IU group on the third day (p less than 0.01). Similarly, the serum estradiol level decreased in the oPRL-treated groups on the first day and was restored on the second day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098549 TI - Evaluation of GnRH administration on the prolactin response to thyrotrophin releasing hormone in normal women. AB - To determine whether GnRH modifies prolactin (PRL) secretion in response to thyrotrophin-releasing hormone (TRH) in normal women, a group of eleven normal women, 23 to 40 years of age, was studied in the mid-follicular phase of the menstrual cycle. The PRL response to TRH was evaluated in serum under control conditions and after GnRH infusion. GnRH administration augmented basal PRL release and amplified TRH-induced PRL release. These results suggest that GnRH may be involved in PRL release, partly by increasing the sensitivity of the lactotrophs to TRH. PMID- 3098550 TI - Response of growth hormone release to human growth hormone-releasing factor and its analogs in the bovine. AB - Responses of growth hormone (GH) release to synthetic human growth hormone releasing factor (hGRF)-44-NH2 analogs were determined, and the GH-releasing potency based on dose per kg of body weight (bw) was compared with that of hGRF 44-NH2 in female dairy calves. Four- and 12-month-old calves were injected intravenously with 0.25 microgram of hGRF-44-NH2 or its analogs per kg of bw. Blood samples were collected before, and during 180 min after each injection, and plasma GH concentrations were measured by radioimmunoassay. Areas under the GH response curves for 180 min after injection of hGRF-44-NH2 and its analogs were used as an index of the GH-releasing potency of each peptide. The GH-releasing potency of hGRF(1-26)-NH2 was significantly lower than that of hGRF-44-NH2 (P less than 0.05). On the other hand, hGRF(1-29)-NH2 possessed similar potency to hGRF-44-NH2. [D-Tyr1]-hGRF-44-NH2 showed prolonged GH-releasing activity, though its potency was similar to that of hGRF-44-NH2. Also, [D-Ala2]-hGRF(1-29)-NH2 exhibited prolonged GH-releasing activity, and its potency was 2.5 (P less than 0.05) and twice (P less than 0.05) as great as that of hGRF-44-NH2 and hGRF(1-29) NH2, respectively. These results demonstrate that the N-terminal 29 amino acid residues of hGRF possess the activity site required for full GH release in vivo, and [D-Ala2]-hGRF(1-29)-NH2 has longer and greater activity, on a dose basis, than hGRF-44-NH2 in the calves. PMID- 3098551 TI - Sleep studies in benign epilepsy of childhood with rolandic spikes. I. Sleep pathology. AB - Polygraphic all-night sleep records of 11 children with typical benign epilepsy of childhood with rolandic spikes (BERS) and those of eight nonepileptic controls were investigated with regard to sleep pathology. Basic properties of sleep organization and electromorphology were preserved in both groups. Seventeen quantitative sleep parameters were measured. Except for more waking in the BERS group, no sleep parameter showed significant differences between the BERS and the control group, but differences existed in comparison to normative values. We interpret our results as showing that in BERS epileptic neuronal malfunctioning does not affect sleep organization in a characteristic manner. The lack of detrimental interactions between epileptic neuronal behavior and pathological sleep alterations may be an additional cause of the benign course of BERS. PMID- 3098552 TI - Sleep studies in benign epilepsy of childhood with rolandic spikes. II. Analysis of discharge frequency and its relation to sleep dynamics. AB - Polygraphic all-night sleep recordings of 11 children with benign epilepsy of childhood with rolandic spikes (BERS) were investigated from the viewpoint of spike distribution. Spike/min ratios were calculated with regard to different sleep stages and waking, identical stages of the consecutive cycles, and stages 1 2 taking place on the descending versus the ascending slopes of sleep cycles. Maximum spike/min ratios were related to slow sleep stages, especially delta sleep, and in general to the first cycle. Stages 1-2 on the descending (DESC) slopes of consecutive cycles showed a decrease in spike density during the night, as opposed to the increasing rate of activation of the same stages on the ascending (ASC) slopes. Based on our results, we suggest that the actual drive of spiking as well as seizures in BERS is the functional overweight of sleep inducing mechanisms. PMID- 3098554 TI - Epilepsy and verbosity. AB - Stories were elicited from 29 epileptic patients with generalized, simple partial, and complex partial seizures with bilateral, right, or left foci, and from 32 persons in two control groups. Four older epileptic patients with long histories of left complex partial seizures were verbose. Their stories involved trivial and subjective details, consistent with circumstantiality and suggesting the substrate for a hallucinatory syndrome. PMID- 3098553 TI - Response of multiple seizure types to corpus callosum section. AB - Twenty-four patients (16 men, 8 women) underwent corpus callosum section specifically for improvement of control of atonic or tonic seizures that resulted in falls and injuries. All patients suffered from multiple seizure types, including complex partial (CP) and tonic-clonic (TC) seizures, in addition to the tonic or atonic episodes. Preoperative seizure frequency was quantified for all types for 1 year immediately before surgery and for the most recent year since the procedure; average monthly counts were obtained for each seizure type. The period of follow-up since surgery averaged 43 months (range, 23-79 months). Statistically significant improvements were documented, not only for the atonic/tonic seizures (p less than 0.0001) for all patients, but also for TC seizures (17 patients; p less than 0.001) and CP seizures (20 patients; p less than 0.02). Six patients experienced an exacerbation of CP seizures postoperatively, and three developed new simple partial (SP) seizures. In all of the CP group and all three of the SP group, ictal video and EEG features suggested that the new seizures were an aborted expression of the previously generalized seizures. From these data, we conclude that callosotomy is an effective treatment for tonic, atonic, and TC seizures intractable to anticonvulsant medications. Three patients became seizure free. The procedure may also be useful for certain specific subgroups of CP epilepsy, but further studies are required before expanding callosotomy to intractable CP seizures not amenable to focal resection. PMID- 3098555 TI - Carbamazepine versus phenobarbital for partial onset seizures in children. AB - Thirty-nine children were treated with either phenobarbital (PB) or carbamazepine (CBZ) for newly diagnosed partial onset seizures. Drug selection was randomized in 33 subjects. Parents and the psychologist evaluating the child were blind to drug identity. Psychometric and behavioral evaluations were done at intake and at 6- and 12-month follow-ups. There were no significant differences between drugs in effect on behavior or cognitive function. CBZ caused more systemic problems. There was a trend toward better seizure control with CBZ, but this was not statistically significant. Although individual children in each group had changes in behavior or cognitive status, neither group changed significantly, in either acute or chronic follow-up. PMID- 3098556 TI - Zonisamide (CI-912) and cognition: results from preliminary study. AB - Nine patients with refractory partial seizures were evaluated in a pilot study of a new anticonvulsant compound, zonisamide (1,2-benzisoxazole-3 methanesulfonamide; CI-912). Cognitive functioning was evaluated prior to treatment with zonisamide and repeated after 12 and 24 weeks of treatment with zonisamide. At minimum steady-state plasma concentrations greater than 30 micrograms/ml, zonisamide appeared to affect specific cognitive functions such as acquisition and consolidation of new information. Previously learned material, such as vocabulary, and psychomotor performance were not affected. Verbal learning was affected, while visual-perceptual learning was unimpaired. These cognitive effects were observed in the absence of the usual clinical signs and symptoms of toxicity. A linear relationship was found between impairment of cognitive abilities and the minimum plasma concentration (r = -0.73; p less than 0.05). Findings also suggest the development of tolerance to the adverse cognitive effects. PMID- 3098557 TI - Pharmacokinetic interactions of progabide with other antiepileptic drugs. AB - The influence of progabide, a new antiepileptic drug, on the pharmacokinetic profiles of phenobarbital, phenytoin, carbamazepine, and valproic acid was evaluated in four separate studies, each including six young healthy volunteers. The pharmacokinetic parameters of the associated antiepileptic drugs were measured before and after repeated administration of progabide (600 mg t.i.d.) for 15 days. A significant reduction of the total body clearance of both phenytoin and phenobarbital and a higher Cmax value of carbamazepine epoxide and phenobarbital were observed. No modifications were noticed for the kinetic profiles of carbamazepine and valproic acid. These modifications may be of clinical relevance and suggest that, as a general rule, when progabide is added to an established treatment with phenobarbital or phenytoin or carbamazepine, an adjustment of previous posology may be necessary. PMID- 3098558 TI - On the association of the HLA system with epilepsy in children. AB - HLA typing was done in 51 unrelated children with epilepsy of unknown origin. The frequency of the antigens of the loci A, B, C, and DR were compared with control groups as follows: (1,085 for the loci A and B, and 200 for C and DR). Statistically significant increased frequency of HLA-DR5 (X2 = 13.08, p less than 0.001) in the patients was demonstrated. Association between HLA-DR5 with different type of seizures was not found in this study. PMID- 3098559 TI - Expression of a family of psbA genes encoding a photosystem II polypeptide in the cyanobacterium Anacystis nidulans R2. AB - The genome of the cyanobacterium Anacystis nidulans R2 contains three genes (psbA) for the QB protein of photosystem II. This protein is essential for oxygenic photosynthetic electron tansport, and is the target for several herbicides which act by binding directly to the photosynthetic apparatus. Transcripts from the three Anacystis psbA genes are present in wild-type cells at different steady-state levels. The nucleotide sequences of two of the genes, psbAII and psbAIII, predict a protein having the same amino acid sequence which differs from that of the psbAI gene by 25 (out of 360) residues. Inactivation of each of the psbA genes in the Anacystis chromosome, singly or in pairs, shows that each of the genes is capable of producing sufficient functional QB protein to support normal photoautotrophic growth. PMID- 3098560 TI - Evolution of biosynthetic pathways: a common ancestor for threonine synthase, threonine dehydratase and D-serine dehydratase. AB - The Bacillus subtilis genes encoding threonine synthase (thrC) and homoserine kinase (thrB) have been cloned via complementation of Escherichia coli thr mutants. Determination of their nucleotide sequences indicates that the thrC stop codon overlaps the thrB start codon; this genetic organization suggests that the two genes belong to the same operon, as in E. coli. However, the gene order is thrC-thrB in B. subtilis whereas it is thrB-thrC in the thr operon of E. coli. This inversion of the thrC and thrB genes between E. coli and B. subtilis is indicative of a possible independent construction of the thr operon in these two organisms. In other respects, comparison of the predicted amino acid sequences of the B. subtilis and E. coli threonine synthases with that of Saccharomyces cerevisiae threonine dehydratase and that of E. coli D-serine dehydratase revealed extensive homologies between these pyridoxal phosphate-dependent enzymes. This sequence homology, which correlates with similarities in the catalytic mechanisms of these enzymes, indicates that these proteins, catalyzing different reactions in different metabolic pathways, may have evolved from a common ancestor. PMID- 3098561 TI - Primary structure of the chromosomal protein HMb from the archaebacteria Methanosarcina barkeri. AB - The amino acid sequence of the protein HMb, a protein of 93 residues (Mr 10757) which represents the major acid-soluble component of the Methanosarcina barkeri nucleoprotein complex, has been established from automated sequence analysis of the protein and from structural data provided by peptides derived from cleavage of the protein at aspartic acid, arginine and methionine residues. The protein HMb is mainly characterized by a high amount of charged residues (15% of acidic residues and 26.8% of basic residues) which are distributed all along the polypeptide chain. The amino acid sequence of the protein HMb is not homologous to any eubacterial, archaebacterial or eukaryotic chromosomal proteins known up to now. PMID- 3098562 TI - Involvement of cis and trans Golgi apparatus elements in the intracellular sorting and targeting of acid hydrolases to lysosomes. AB - To delineate the traffic route through the Golgi apparatus followed by newly synthesized lysosomal enzymes, we subfractionated the Golgi apparatus of rat liver by preparative free-flow electrophoresis into cisternae fractions of increasing content of trans face markers and decreasing contents of markers for the cis face. NADPase was used to mark median cisternae. Beta-Hexosaminidase, the high mannose oligosaccharide processing enzyme, alpha-mannosidase II, the two enzymes involved in the biosynthesis of the phosphomannosyl recognition marker, and the phosphomannosyl receptor itself decreased in specific activity or amount from cis to trans. Additionally, these activities were observed in a fraction consisting predominantly of cisternae, vesicles and tubules derived from trans most Golgi apparatus elements. These results, along with preliminary pulse labeling kinetic data for the phosphomannosyl receptor, suggest that lysosomal enzymes enter the Golgi apparatus at the cis face, are phosphorylated, and appear in trans face vesicles by a route whereby the phosphomannosyl receptor bypasses at least some median and/or trans Golgi apparatus cisternae. PMID- 3098563 TI - Dose-response scrutiny of coronary vasodilation after intracoronary verapamil in man. A quantitative cineangiographic study. AB - The effect of various doses of intracoronary verapamil on the diameter of angiographically normal left coronary artery segments was investigated in 22 patients with and without coronary atherosclerosis by quantitative angiography. Very low doses (50 micrograms) were given in 3 patients; doses of 250 micrograms, 350 micrograms and 500 micrograms were administered in 7, 6 and 13 patients, respectively. A single dose was administered in 15 patients, while two increasing doses of verapamil were tested in 7. The effect of verapamil was compared in each patient with that of nitroglycerin (NG; 0.6 mg), administered sublingually in all as the last step of the study. An additional group of 8 patients served as the control. These patients received 4 intracoronary injections of contrast medium without drugs and a fifth injection following 0.6 mg of sublingual NG. In the control group no significant changes in coronary artery diameter were observed following the four control injections of contrast medium, while a 18 +/- 9% increase in vascular diameter was observed following NG. When verapamil was injected a dose-dependent vasodilation was observed, which began to be significant with doses higher than 250 micrograms. Mean percent variations of coronary artery diameter relative to control were -0.2 +/- 3.6%, 4.6 +/- 5.5%, 11.4 +/- 7.5% and 19.9 +/- 10.7%, in response to verapamil doses of 50, 250, 350 and 500 micrograms, respectively. Subsequent nitroglycerin induced a 21.5 +/- 10.7% mean percent coronary artery dilation (NS vs verapamil 500 micrograms and vs NG in the control group). Thus, verapamil induced a dose-dependent coronary vasodilation which at a dose of 500 micrograms was comparable to that induced by NG. Both with verapamil and NG the smallest vessels exhibited the greatest vasodilation. It is concluded that at the doses used in this study, injection of verapamil into the left coronary artery is safe and markedly decreases tone in the large coronary arteries. This finding supports the use of verapamil in clinical conditions in which the role of coronary vasoconstriction is proven or thought to be relevant. PMID- 3098564 TI - Left ventricular end-systolic pressure volume relations in healthy young men. AB - The purpose of the present study was to establish the relationship of left ventricular end-systolic volume vs. mean systemic pressure in variously afterloaded beats in a group of healthy, young, men (n = 6, age 24 +/- 0.9 years). The relationship was expressed by the slope (Emax) of the line connecting pressure-volume co-ordinates and its extrapolated intercept (Vd) of the volume axis. The slope was calculated by linear regression of mean systemic arterial pressure (mean SAP, measured by catheter in the radial artery) vs. end-systolic left ventricular volume (ESV, estimated from cross-sectional, 4-chamber echocardiographic images). Recordings were obtained at resting, reduced (nitroglycerin infusion), and elevated (metaoxedrin infusion) blood pressure. Individual Emax values ranged from 1.05 to 2.01 mmHg ml-1; Vd was consistently found to be negative, ranging from -4.7 to -54.8 ml. All individual relations were statistically significant (P less than 0.05 to P less than 0.001). Group values were Emax = 1.27 +/- 0.25 (SE) mmHg ml-1, Vd = -43.3 +/- 7.5 (SE) ml, and Emax indexed for body surface area, Emax ind = 2.54 +/- 0.49 (SE) mmHg ml-1 m-2. We further examined the validity of proposed optimal relations among Emax, heart rate (HR) and systemic resistance (Rs): Emax/HR = Rs, and among ejection fraction (EF), EDV and Vd: EF = 0.5 (1 - EDV/Vd). For the group Emax/HR = 0.023 +/- 0.003 and Rs = 0.016 +/- 0.004 (mmHg ml-1 min-1), i.e., a deviation from equivalence of 30% (P less than 0.001). EF (= 0.72 +/- 0.02) deviated by 18% (P less than 0.001) from its proposed optimum (0.5 (1 - Vd/EDV) = 0.61 +/- 0.06). PMID- 3098565 TI - Kinetics of indium-oxine labelled red cells in haemolytic anaemias. AB - Indium-labelling of red cells is hampered by its high elution rate and short physical half-life. From a study of 23 pathological cases, it is demonstrated that the simultaneous study of 111In- and 51Cr-labelled red cells could only be useful in haemolytic anaemias in which the mechanisms (corpuscular or extra corpuscular) of the cell destruction is in question. PMID- 3098566 TI - A comparative distribution study of 111In-labeled DTPA and TTHA monoclonal antibody conjugates in a choriocarcinoma xenograft model. AB - Conjugates of the chelating agents DTPA and TTHA with a monoclonal anti-HCG were prepared. The tissue distribution of the 111In-labeled conjugates and also 111In citrate was studied in mice bearing human choriocarcinoma xenografts. The antibody conjugates both gave high liver and spleen radionuclide accumulation. Elevated femur levels were observed for the TTHA conjugate and 111In-citrate. Generally the DTPA conjugate showed the highest tumor/tissue ratios, although its tumor/blood ratio was lower than the other two materials. The results infer that the DTPA conjugate has the greatest utility as an imaging agent but that it would require a background subtraction technique. PMID- 3098567 TI - Increased chromosomal breakage in epileptic children after long-term treatment. AB - To investigate the mutagenic effects of antiepileptic drugs (AED), 39 epileptic children treated by long-term monotherapy (10 cases with Pb, 11 with Cbz, 9 with Vpa, 8 with Pht) have been studied. The long-term administration was monitored by measurement of AED serum concentrations by gaschromatography. Metaphase chromosome observations were performed using short time culture of peripheral blood lymphocytes and 100 mitoses from each proband were analyzed. A significant increase of CA in the group of patients with Pb (0.23), Cbz (0.19), Vpa (0.25), Pht (0.18) as compared with those of nine epileptic children without treatment (0.08) has been found. Because unrepaired damage of DNA may act as a possible carcinogenic potential, the shortest possible duration of AED treatment is recommended. PMID- 3098568 TI - [Arachidonic acid metabolism following aneurysm rupture]. AB - Imbalance between the two arachidonic acid metabolites, prostacyclin (PGI2) and thromboxane A2 (TXA2), is thought to be at least in part responsible for the development of cerebral vasospasm following aneurysm rupture. In 12 patients with subarachnoid hemorrhage the pre- and postoperative serum and CSF levels of PGI2 and TXA2 were measured as a function of their stable hydrolysis products, 6-Keto PGF1 alpha (PGI2) and thromboxane B2 (TXA2), with a highly specific radioimmunoassay. Serum levels of both metabolites were elevated in half of the patients, but no correlation to the clinical course could be found. However, TXB2 concentration in the CSF was significantly increased preoperatively with close correlation to the amount of intracisternal blood, as detected by CT scan. Furthermore, it could be demonstrated that the postoperative course of the TXB2 concentrations in the CSF reflects the clinical course in such a way that a characteristic secondary rise of TXB2, concentration postoperatively is closely related to the occurrence of cerebral vasospasm and clinical deterioration. The conclusion is drawn that measurement of arachidonic acid metabolites in the CSF may provide important information concerning the pathophysiological events following subarachnoid hemorrhage, especially with regard to incipient cerebral vasospasm. PMID- 3098569 TI - Mortality in rats on long-term parenteral nutrition. AB - The long-term effect of total parenteral nutrition (TPN) was studied in rats. A failure to thrive developed and all animals died within 40 days of TPN. Autopsy invariably demonstrated the increased weight and volume of the liver and spleen. Multiple fat emboli were found in the lungs of all animals, and multiple epithelioid cell granulomas in the liver of all and in the spleen of most animals. Chronical low grade infection could not be demonstrated. Microorganisms were not found in blood or tissue specimens and endotoxin could not be demonstrated in plasma samples. PMID- 3098570 TI - Evidence of the involvement of dopamine in the analgesic effect of nefopam. AB - The involvement of brain monoamines in the mechanism of action of nefopam, a new analgesic, was investigated in rats. The study was designed to evaluate the effect of various means of impairing monoaminergic transmission on nefopam analgesia as measured with the hot plate method. Pretreatment with reserpine (2 mg/kg) significantly reduced the antinociceptive action of nefopam (40 mg/kg), indicating that the interaction of this drug with the monoaminergic systems is important for its effects. A role for serotonin (5-HT) or norepinephrine (NE) was ruled out by the fact that selective depletion of 5-HT (using 5,7 dihydroxytryptamine) or NE (using DSP-4 or FLA-63) did not affect nefopam analgesia. A significant reduction of the effect of nefopam was found in rats pretreated with 6-hydroxydopamine (6-OHDA). Also 6-OHDA plus desipramine, which selectively depleted brain DA, markedly reduced the antinociceptive effect of nefopam. The data strongly suggest that a critical dopaminergic synapse is involved in the mechanism by which nefopam inhibits nociceptive responses in rats. PMID- 3098571 TI - Stereospecific regulation of [3H]inositol monophosphate accumulation by calcium channel drugs from all three main chemical classes. AB - Depolarization of [3H]inositol-prelabelled rat cortical slices through the elevation of extracellular K+ levels leads to increased accumulation of [3H]inositol phosphates. In the presence of 18 mM K+, Ca2+ channel activators selectively stimulated the formation of [3H]inositol monophosphate ([3H]IP1) whereas Ca2+ channel blockers were inhibitory. Blockade of the Na+ channel by 1 microM tetrodotoxin had no effect but chelation of extracellular Ca2+ abolished the response. The enantiomers of the benzoxadiazol 1,4-dihydropyridine 202-791 showed opposite stereospecific regulation of [3H]IP1 formation: (+)-(S)-202-791 stimulated (252%; ED50: 88 nM), whereas (-)-(R)-202-791 inhibited (65% inhibition, ED50: 602 nM). The (-) enantiomer of Bay K 8644 was a potent [3H]IP1 stimulator (258%; ED50: 82 nM). While (+)-Bay K 8644 was inactive in the presence of 18 mM K+, it completely inhibited the (-)-Bay K 8644-induced stimulation with a Ki of 103 nM. Representatives of the other two main classes of Ca2+ channel blockers (phenylalkylamines and benzothiazepines) inhibited K+ depolarization induced and (-)-Bay K 8644 enhanced [3H]IP1 formation in a dose-dependent, stereospecific manner. The results show that Ca2+ channel blockers are efficient modulators of depolarization-induced and Ca2+ channel activator-induced [3H]inositol monophosphate formation in brain, and demonstrate the functional coupling of three distinct drug receptor sites on neuronal Ca2+ channels. PMID- 3098572 TI - The synthesis of eicosanoids induced by anaphylaxis in guinea-pig isolated lungs perfused via the trachea. AB - We have monitored the release of prostanoids and leukotrienes from isolated lungs taken from previously sensitized guinea-pigs perfused either via the pulmonary artery or via the trachea. The eicosanoids were monitored by direct radioimmunoassay and further identified by bioassay and radioimmunoassay following separation by RP-HPLC. When ovalbumin is delivered via the trachea it releases more cyclo-oxygenase products (3-fold) and lipoxygenase products (10 fold) than when delivered via the pulmonary circulation. Indomethacin enhanced leukotriene release whereas BW755C did not affect the release of leukotrienes induced by ovalbumin. These results suggest that perfusing the lungs via the trachea might be relevant for the study of anaphylaxis and other conditions in which the pathophysiological development is determined by cells closer to the alveolar surface in the lung. PMID- 3098573 TI - Evidence for serotonin-S2 receptor involvement in analgesia in humans. AB - The possible analgesic activity of ritanserin (a new very selective and potent serotonin-S2 antagonist) was studied (double-blind) in humans. A significant increase in nociceptive flexion reflex threshold and subjective pain threshold was observed after five days of treatment, while treatment with placebo did not induce any change. The effects of ritanserin were not reversed by either naloxone or saline (double-blind) administration. Our data suggest a possible role of serotonin-S2 receptors in analgesia. PMID- 3098574 TI - Interference of phorbolesters with endothelium-dependent vascular smooth muscle relaxation. AB - Histamine-induced endothelium-dependent relaxation (EDR) in the pulmonary artery was inhibited in a concentration-dependent manner by the phorbolester phorbol 12,13-dibutyrate (PDBu) (IC50: 70 nM) whereas EDR occurring in response to ionophore A 23187 was not affected by PDBu. The phorbolester 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), which does not activate protein kinase C (PKC), was without effect on receptor- or ionophore-induced EDR. The observed inhibition of signal transduction by PKC activation is suggested to reflect phosphorylation of the GTP binding protein Ni. PMID- 3098575 TI - Basic proteins in the human aortic intima: nonequilibrium two-dimensional electrophoretic analysis of tissue extracts. AB - The protein composition of atheroma-free human thoracic intima was compared with that containing fatty streaks or fibro-fatty lesions utilizing two-dimensional gel electrophoresis (2-DE) and silver staining. Intimal proteins extracted with 9 M urea were separated by nonequilibrium pH gradient electrophoresis (NEPHGE) followed by polyacrylamide gel electrophoresis (PAGE) in the second dimension. NEPHGE-PAGE of proteins extracted from atheroma-free intima revealed several major proteins: actin, tropomyosin-like proteins, proteins with relative molecular weight (Mr) of 250,000 (P250), two proteins with Mr about 15,000 (P15a, P15b), and many medium proteins such as a myosin heavy chain, two myosin light chains, and proteins P47, P44, P32, P27, P20a, P20b, P19a, P19b. Several additional proteins were observed in intimas with fatty streaks and fibro-fatty lesions. Most of them, such as albumin, transferrin, Apo A-I, alpha 1 antitrypsin, fibrinogen beta-chain, IgG, appear to originate from plasma. Differences in protein composition of intima with fibro-fatty streaks compared with adjacent lesion-free intima varied from case to case and need further study. NEPHGE-PAGE in combination with isoelectric focusing (ISO)-PAGE revealed more intimal proteins in atheroma-free and diseased aortas than either method alone, proteins which might be quantitated, isolated for binding studies, and further evaluated for their potential role in atherogenesis. PMID- 3098576 TI - Preliminary studies on bacteriophage typing of Mycobacterium tuberculosis strains isolated in Salamanca (Spain). AB - A phage typing of 202 strains of Mycobacterium tuberculosis isolated in Central and Northwest Spain was carried out. The commonest phage type was A (64%) and within this type A (45%). This was followed in frequency by phage type B (26%) and in last place type I (10%). No relationship was observed between the phage type and the geographical or anatomical origin of the strains. PMID- 3098577 TI - Prevalence of protease and elastase production by clinical isolates of Pseudomonas aeruginosa in relation to aeruginocine typing patterns. AB - Sixty six consecutive P. aeruginosa isolates from heterogeneous clinical specimens were subjected to aeruginocine (pyocine) typing and assayed for in vitro protease and elastase production by a simple and reproducible qualitative test. The 45.4% of the clinical isolates were found to be both protease and elastase (P + E +) producers; 40.9% were only protease producers (P + E -) and 13.6% were non producers (P - E -). Aeruginocine code 7777 strains were found to be predominant among P + E + and P + E - types, as 48.2% and 51.7% isolates belonged to the types, respectively, suggesting thereby the virulence of this aeruginocine type in P. aeruginosa infections and the possible association of protease and elastase production with aeruginocine production. PMID- 3098578 TI - Plasmid profile of penicillinase-producing Neisseria gonorrhoeae in Greece. AB - Four plasmid patterns were detected in thirteen strains of beta-lactamase producing Neisseria gonorrhoeae isolated in Greece. Nine strains harbored the 4.5 Mdal penicillin-resistance plasmid with or without a 24.5 Mdal conjugative plasmid, two strains carried the 3.2 Mdal penicillin-resistance plasmid and two strains the new combination of the 3.2 Mdal penicillin-resistance plasmid and the conjugative plasmid (24.5 Mdal). Conjugal transfer experiments between Neisseria gonorrhoeae and E. coli revealed that beta-lactamase activity was acquired by recipient E. coli. The 4.5 and 3.2 Mdal penicillin-resistance plasmids were detected in the transconjugants by agarose gel electrophoresis, but co-transfer of the conjugative plasmid did not occur. The auxotypes and plasmid profiles were also compared. PMID- 3098579 TI - Lipid peroxidation in regenerating rat liver. AB - Rats entrained to a strictly regulated lighting and feeding schedule have been subjected to partial hepatectomy or a sham operation. In the partially hepatectomised animals the period of liver regeneration is characterised by regular bursts of thymidine kinase activity. Liver microsomes from rats, at times corresponding to maximum thymidine kinase activity, have much reduced rates of lipid peroxidation compared to control preparations: this is due in part to increased levels of lipid-soluble antioxidant at times of maximal DNA synthesis. This temporal relationship between thymidine kinase and lipid peroxidation is consistent with the view that lipid peroxidation is decreased prior to cell division. PMID- 3098580 TI - Cyclooxygenase-catalyzed formation of 9-hydroxylinoleic acid by guinea pig alveolar macrophages under non-stimulated conditions. AB - Data are presented on the formation of a linoleic acid oxygenation product under basal conditions by guinea pig alveolar macrophages (AM). Under non-stimulated conditions 20 X 10(6) AM released about 1 nmol 9-hydroxylinoleic acid (9-HODE) during a 15 min incubation. Furthermore, AM released more than 2 nmol 12-hydroxy 5,8,10-heptadecatrienoic acid (HHT), a byproduct of the formation of thromboxane A2. 9-HODE and HHT were the most prominent products formed under the incubation conditions used. These products were formed via a cyclooxygenase-catalyzed reaction, since their formation was inhibited by 1 microM indomethacin. Thus, under basal conditions AM possess substantial cyclooxygenase activity. The biological significance of 9-HODE and related substances is discussed. PMID- 3098581 TI - Origins of stereospecificity in DNA damage by anti-benzo[a]pyrene diol-epoxides. A molecular modelling study. AB - A general computational procedure for the modelling of intercalated DNA-ligand complexes has been developed, and is used here to model intercalated complexes of the (+)-anti and (-)-anti enantiomers of benzo[a]pyrene diol-epoxide (BPDE) with cytosine-3',5'-guanosine double-stranded DNA sequences (dCpG). Results are presented indicating differences between the behaviours of the two enantiomers which have implications for the understanding of the stereospecificity of DNA strand breakage by benzo[a]pyrene diol-epoxides. PMID- 3098582 TI - Amino acid sequence determination of guanyl-specific ribonuclease Sa from Streptomyces aureofaciens. AB - Using automated Edman degradation of two nonfractionated peptide mixtures of tryptic and staphylococcal protease digests of the protein, the complete amino acid sequence of the guanyl-specific ribonuclease Sa from Streptomyces aureofaciens was established. Ribonuclease Sa contains 96 amino acid residues (Mr 10,566). A 50% sequence homology of ribonuclease Sa to the guanyl-specific ribonuclease St from S. erythreus was found. PMID- 3098583 TI - A unique nucleoprotein structure associated with the Drosophila melanogaster 18 28 S rDNA nontranscribed spacer. AB - We have detected unique nucleoprotein particles specific for the 18-28 S rDNA nontranscribed spacer of Drosophila melanogaster. The particles migrate between di- and trinucleosomes on nucleoprotein gels, and are between mono- and dinucleosomal in DNA length. These migration properties suggest that the nontranscribed spacer particles could have a protein component larger than a histone core. The variant nucleoprotein structures map primarily within the nontranscribed spacer 235 base pair internal subrepeat, which is AT-rich and possesses a 50 base pair sequence homologous to the RNA polymerase I binding site. PMID- 3098584 TI - Endocrine changes in the late-follicular and postovulatory intervals as determinants of the in vitro fertilization pregnancy rate. AB - This investigation examines the hormone pattern in in vitro fertilization (IVF) cycles from the time of human chorionic gonadotropin (hCG) administration through embryo transfer to ascertain whether the absolute levels or secretory patterns of the major reproductive hormones affect the IVF pregnancy rate. Thirty-one women who underwent IVF treatment were enrolled in the study. All patients received clomiphene citrate/human menopausal gonadotropin for ovulation induction. Significant elevations in serum estradiol (E2) levels in the pregnant group were found throughout the cycle interval studied. After hCG administration the serum hCG levels were not different between the groups. Significant elevations in serum progesterone (P) concentrations were found in the pregnant group from the day after laparoscopy through embryo transfer. Embryos obtained from the pregnant group appeared to be different in that the mean number of blastomeres per embryo transferred was significantly greater. Therefore for achievement of an IVF pregnancy the optimal hormone pattern employing combination ovulation induction in the ovulation to transfer interval is a relatively high E2 level in ovulation followed by a high P level at transfer and into the luteal phase. These elevated hormone levels do not depend on the response to exogenous hCG. PMID- 3098585 TI - The effects of inducing a follicular phase gonadotropin secretory pattern in normal women during the luteal phase. AB - It has been hypothesized that the slowing of the luteinizing hormone (LH) pulse frequency in the luteal phase may be necessary for the demise of the corpus luteum, the intercycle rise in baseline follicle-stimulating hormone (FSH), or ovarian follicular development in the subsequent cycle. For assessment of the physiologic role of the luteal phase LH pulse pattern, this pattern was converted to a follicular pattern in six normal women who used exogenous gonadotropin releasing hormone administered with a portable pump (dose 50 to 100 ng/kg subcutaneously every 90 minutes beginning in the early luteal [n = 3] and midluteal [n = 3] cycle phases). There was no significant difference between the treated and the subsequent cycle for luteal progesterone production [186.3 versus 159.0 (ng/ml) day], preovulatory follicular size (23.1 versus 22.5 mm), estradiol levels, luteal phase length (15.6 versus 14.3 days), and daily gonadotropin concentrations including the intercycle FSH rise (160.5 versus 139.1 ng/ml). A follicular phase gonadotropin pulse pattern (increased frequency, decreased amplitude) in the luteal phase had no discernible effects on the corpus luteum or on follicular development in the subsequent cycle. PMID- 3098586 TI - Follicular growth in relation to serum hormonal patterns in adolescent compared with adult menstrual cycles. AB - The purpose of this study was to clarify the endocrine regulation of the adolescent menstrual cycle, especially the relationships between ovarian follicular development, luteal phase progesterone secretion, and function of the hypothalamic-pituitary unit. One menstrual cycle of each of 17 women who were 15 and 16 years of age and 12 women who were 25 to 35 years of age was characterized by ultrasonography and hormone measurements. In both groups there was a close correlation between follicle size and serum estradiol concentrations. In the adolescents, follicle development was slower, and an eventual ovulation took place from a smaller follicle than in the older group. The immediate preovulatory follicle size correlated with the maximal serum progesterone concentration during the luteal phase. Late follicular development in adolescents may be related to the slow increase of serum follicle-stimulating hormone concentrations early in the cycle. PMID- 3098588 TI - Brophy: just another right to die case? PMID- 3098587 TI - Tissue plasminogen activator: a new advancement in fibrinolytic therapy. PMID- 3098589 TI - Insulin administration in diabetic ketoacidosis. PMID- 3098590 TI - [Comparative studies between excretion of 5-S-cysteinyldopa and indole melanogens in urine]. PMID- 3098591 TI - Neurofibromatosis in a scar. PMID- 3098592 TI - Parenteral nutrition and infusion technology. PMID- 3098593 TI - Immunological relationship between the hydrophobic fraction of proteose-peptone and the milk fat globule membrane of bovine milk. AB - The antigenic relationship between the milk fat globule membrane (MFGM) and the hydrophobic fraction of proteose-peptone (HFPP) was demonstrated, using a mono specific anti-HFPP antibody. PMID- 3098594 TI - Inhibition of cell migration in sea urchin embryos by beta-D-xyloside. AB - This investigation examines the effect of exogenous xylosides on primary mesenchyme cell behavior in Strongylocentrotus purpuratus embryos. In confirmation of studies in some other species the addition of 2 mM p-nitrophenyl beta-D-xylopyranoside blocks the migration but not the initial ingression of primary mesenchyme cells. The blastocoel matrix of treated embryos appears deficient in a 15- to 30-nm-diameter granular component that is observed extensively on the basal lamina and on filopodia of migrating primary mesenchyme cells in untreated embryos. Other blastocoel components appear unaffected by ultrastructural criteria. The incorporation of 35SO4(2-) per embryo into ethanol precipitates of isolated blastocoel matrices was reduced significantly after xyloside treatment but the distribution of 35SO4(2-) after polyacrylamide gel electrophoresis or the glycosaminoglycan composition was unaffected. Chromatography on Sepharose CL-2B demonstrates a reduction in size of sulfated components of the blastocoel. While over 60% of the 35S-labeled material from the blastocoel of normal mesenchyme blastulae is voided from a Sepharose CL-2B column run in a dissociative solvent, only 10% from xyloside treated embryos is voided. Instead, there is a large included peak with Kav of 0.33. This material is acid soluble but cetylpyridinium chloride precipitable. It apparently consists largely of free glycosaminoglycan chains. Based on analysis of chondroitinase ABC digestion products this material consists of 41% chondroitin-6-sulfate and 58% dermatan sulfate. These results are consistent with a role in cell migration for intact chondroitin sulfate/dermatan sulfate proteoglycans in the sea urchin blastocoel matrix. PMID- 3098595 TI - Mutations affecting dosage compensation in Drosophila melanogaster: effects in the germline. AB - Dosage compensation is the process by which the total amount of gene products of X-linked genes is equalized in females (2X;2A) and males (X;2A). The achievement of dosage compensation takes place at the transcriptional level. Mutations have been isolated that impair the dosage compensation process. These mutations are the male-specific lethals msl-1, msl-2, and mle, which have been analyzed in the somatic tissues. Our aim was to know whether these mutations affect the germline. For this purpose, pole cells homozygous for the male-specific lethal mutations were transplanted into wild-type host embryos, and we checked whether the mutant pole cells were capable of forming functional sperm. The results are as follows: the msl-1 and msl-2 genes are not needed in the germline, while the mle gene seems to be required for normal spermatogenesis. PMID- 3098596 TI - Maternal expression of genes that regulate the bithorax complex of Drosophila melanogaster. AB - A relatively large number of genes have been described that are required for the normal spatial expression of the genes of the bithorax complex. Most of these regulators appear to act negatively and are required to prevent indiscriminate expression of bithorax complex (BX-C) functions. In this report we examine five negative BX-C regulators to determine whether these are maternally expressed in germ-line derived cells. The genes studied include Additional sex combs (Asx), Polycomblike (Pcl), Sex comb extra (Sce), Sex comb on midleg (Scm), and lethal(4)29 [l(4)29]. The maternal germ-line dependent expression of each of these genes is assessed by comparison of zygotes from mothers whose functional germ cells carry no wild-type alleles to zygotes from mothers whose germ cells contain one wild-type allele. Because mutant alleles of each of the genes studied are recessive lethals, mosaic females with homozygous or hemizygous mutant germ lines were produced by pole cell transplantation. The results demonstrate that all of the negative regulators tested are expressed in the maternal germ line and all play important roles in the regulation of BX-C activities during embryogenesis. The absence of maternally supplied products from all of the genes studied except l(4)29 can be largely or completely compensated for by the activity in the zygote of a paternally contributed wild-type allele. It is argued that, with the exception of l(4)29, the genes studied in this report are qualitatively similar in function to the previously described BX-C regulators Pc, esc, and sxc. The available evidence indicates that genes within this group have functions that are not restricted to the regulation of genes that control segmental identity. PMID- 3098597 TI - Periodic changes in the rigidity of activated anuran eggs depend on germinal vesicle materials. AB - The eggs of Xenopus laevis and Bufo bufo japonicus matured in vitro by progesterone were denuded and activated by electrical shock or pricking, and their diameters were determined periodically until the postactivation time equivalent to the 8- to 16-cell stage. Normally matured eggs showed a quick rounding-up and flattening immediately after activation (activation response), followed by a periodic flattening and rounding-up (postactivation response) corresponding to the intervals of early cleavage cycles. When denuded eggs that were induced to mature after removal of the germinal vesicle (GV) were activated, they showed a normal activation response, but retained the rounded-up state without exhibiting the periodic postactivation changes. Injection of GV materials back into enucleated Bufo oocytes and determination of the postactivation flattening 120 min after activation revealed that the extent of flattening correlated well with the amount of GV materials injected, provided injection was made before the first polar body was emitted. Thus, postactivation flattening, but not activation flattening, is an active property of eggs established under the influence of the GV and is linked to the periodical changes of rigidity during early cleavage cycles. PMID- 3098598 TI - The spatial distribution of a blastoderm stage-specific mRNA from the serendipity locus of Drosophila melanogaster. AB - The spatial distribution of a blastoderm stage-specific mRNA was examined by hybridization in situ to tissue sections of early embryos of Drosophila melanogaster. The mRNA examined, the C mRNA, is coded for by the molecularly complex locus, serendipity (sry). The C mRNA was found to be expressed in embryos in all nuclei and cells except pole cells, during the syncytial and cellular blastoderm stages and its transcription correlates well with the formation of the cellular blastoderm. PMID- 3098599 TI - Blastoderm-specific and read-through transcription of the sry alpha gene transformed into the Drosophila genome. AB - The serendipity (sry) locus contains three tightly clustered genes: beta, alpha, and delta. The alpha gene lies between beta and delta and is expressed predominantly at the blastoderm stage of embryogenesis. Additional features of this locus include read-through transcription and the fact that the predicted beta and delta polypeptides show remarkable homology to the Xenopus RNA polymerase III transcription factor TFIIIA. To identify cis-acting elements controlling the expression of the alpha and beta transcripts, we created transformed lines containing modified versions of these genes. In lines containing derivatives of both the alpha and beta genes, the expected modified mRNAs are transcribed. An alpha gene variant containing only 798 bp of upstream DNA is also transcribed, and at the proper time; thus blastoderm-specific alpha gene transcription is independent of expression of the adjacent upstream beta gene. Analysis of transformed lines confirmed the beta-alpha read-through transcription, which was eliminated by the insertion of a different polyadenylation site within the coding region of the beta gene. We conclude that the transcription of the beta and alpha genes is independently regulated. PMID- 3098600 TI - Developmental consequences of mutations in the 84B alpha-tubulin gene of Drosophila melanogaster. AB - Developmental effects of six mutations in the gene encoding the majority of alpha tubulin in all tissues at all stages of Drosophila melanogaster development have been examined. All six alleles produce at least partially stable alpha 84B protein. In genetic assays, two of these alleles approximate the null condition. The other four alleles appear to form a graded series of hypomorphs. The two most severe alleles produce a semidominant maternal-effect polyphasic lethality, plus a predominantly larval recessive zygotic lethality. Clonal analysis of one of these alleles suggests it is a cell lethal. Worsening of the lethal phenotype (negative complementation) occurs in most interallelic heterozygotes involving these two mutations. As hemizygotes, the other four alleles are predominantly larval/pupal lethals. Partial complementation is achieved by most interallelic heterozygotes involving these four alleles. Phenotypic defects associated with the six tubulin mutation include disrupted embryos, pseudopupae, pharate adults with defects in various cuticular pattern elements, pharate adults with retarded head development, adults with leg tremors and extremely short life spans, and viable but sterile adults with bristle defects. PMID- 3098601 TI - Distribution of S-phase cells during the regeneration of Drosophila imaginal wing discs. AB - We investigated the distribution of S-phase cells during regeneration of the imaginal wing disc of Drosophila melanogaster following excision of 30 degrees, 90 degrees, and 150 degrees sectors of tissue. The fragments were cultured in adult abdomens for 1-5 days, labeled in vitro with tritiated thymidine, serially sectioned, and subjected to autoradiography. There was negligible thymidine incorporation in unoperated controls and in the undamaged parts of the operated discs, indicating that DNA synthesis in undamaged tissue is terminated during the first day of the culture period. Almost all of the fragments from which tissue had been removed, as well as controls which were simply cut without the removal of any tissue, showed a cluster of labeled cells (blastema) even after only 1 day of culture. The blastemas in control discs were short-lived, with over 50% of these discs showing no blastema by the third day in culture. Blastemas in discs from which sectors were removed were more persistent; the time at which 50% of the fragments no longer showed a blastema was 4 days for the -30 degrees fragments, 5 days for the -90 degrees fragments, and greater than 5 days for the 150 degrees fragments. The average blastema size, measured as number of labeled cells, was directly related to the amount of tissue removed, and in most cases did not change significantly during the culture period. Both wound edges incorporated tritiated thymidine initially and the S-phase cells remained tightly clustered throughout regeneration; maximum blastema width varied from about 8 to 25 cell diameters. The results are consistent with the idea that regenerative cell proliferation is stimulated and maintained by positional information discontinuities, and terminated when these discontinuities are resolved by the addition of an appropriate number of new cells. PMID- 3098602 TI - Region-specific defects in l(1)giant embryos of Drosophila melanogaster. AB - Lack of zygotic expression of the l(1)giant locus (l(1)gt;3A1), produces embryos with defects in abdominal A5, 6, and 7 and within the head. Scanning electron microscopy at the time of segment formation reveals two regions of defects in the segmentation pattern: anteriorly the labial lobe and thoracic segments T1 and T2 are fused; posteriorly, abdominal segments A5-7 are disrupted. The mature embryo shows incomplete head involution and defects within A5-7; fusion of T1 and T2 is no longer observed. Localized cell death within neural and mesodermal tissues is observed at 7 hr of development; later ventral ganglia, A5-7, are missing. Double mutant analyses of l(1)gt with maternal effect lethal mutations and mutations that generate homeotic, segment number, gap, or segment polarity phenotypes indicate that normal activity of l(1)gt is required for differentiation of two embryonic domains: one corresponding to labial, T1 and T2 segments, and the second corresponding to abdominal segments 5, 6, and 7. PMID- 3098603 TI - Evidence for the role of a guanine nucleotide-binding regulatory protein in the zona pellucida-induced mouse sperm acrosome reaction. AB - Recently, it has been demonstrated that mouse sperm contain a protein with properties similar to the inhibitory guanine nucleotide-binding regulatory protein, Gi (Kopf, G. S., Woolkalis, M. J., and Gerton, G. L. 1986. J. Biol. Chem. 261, 7327-7331). Since sperm-zona pellucida interaction represents a specialized form of intercellular communication and signal transduction we examined the role of the mouse sperm Gi-like protein in the zona pellucida induced acrosome reaction using mechanically isolated, structurally intact zonae pellucidae. Sperm capacitated for 90 min in the presence of increasing concentrations of islet-activating protein (IAP) bind to the zona pellucida to a similar extent as control sperm incubated in the absence of this toxin. The zona pellucida-induced acrosome reaction, however, is inhibited in a concentration dependent manner by IAP, with half-maximal effects at 0.1-1.0 ng/ml IAP. IAP does not affect the ability of the sperm to become capacitated, but inhibits the cells from progressing into an intermediate stage prior to the completion of the acrosome reaction. When sperm are capacitated in the presence of 100 microM guanosine-5'-O-(3-thiotriphosphate) for 60 min prior to the addition of IAP during the final 30 min, the IAP-induced inhibition of the zona pellucida-induced acrosome reaction is abolished; capacitation in the presence of 100 microM guanosine-5'-O-(2-thiodiphosphate) does not abolish the inhibitory effects of IAP. The target of the IAP effect on intact sperm appears to be at the level of the Gi-like protein since IAP-catalyzed 32P-ADP-ribosylation of the Mr = 41,000 substrate in detergent extracts of sperm is reduced when intact sperm are preincubated with IAP during capacitation. These data suggest that the mouse sperm Gi-like protein plays an intermediary role in the zona pellucida-induced acrosome reaction. PMID- 3098604 TI - Sequences expressed sex-specifically in Drosophila melanogaster adults. AB - To obtain probes for sex-specific gene regulation during development in D. melanogaster, sequences expressed sex-specifically in adult flies were isolated by differential cDNA hybridization screens of a genomic library. Ten clones define new sex-specifically expressed genes. The remaining three isolates correspond to previously cloned genes encoding female-specific yolk proteins and chorion proteins. The pattern of expression of these genes in sex determination mutants and in germlineless flies, as well as their tissue specificities, permitted us to distinguish transcripts whose expression is dependent on correct sexual development of the soma or the germline. One of the female transcripts is expressed in nurse cells and oocytes. Five of the male-specific sequences are expressed in the testis during spermatogenesis: the remaining one is expressed in the soma. Experiments using a temperature-sensitive allele of tra-2 show that the presence of this male-specific transcript, found only in the adult paragonia, is not affected by temperature shift of X/X; tra-2ts2 adults. This is in contrast to yolk protein genes, which require tra-2 function in the adult for their expression in the female fat body. PMID- 3098605 TI - Single-radial-immunodiffusion potency tests of inactivated influenza vaccines for use in man and animals. AB - Single-radial-immunodiffusion (SRD) provides a sensitive and reproducible in vitro assay for haemagglutinin (HA) concentration in inactivated influenza vaccines. The use of SRD for human influenza vaccine standardization and application for equine and avian influenza vaccines is discussed. In clinical trials, vaccine HA concentration measured by SRD has been shown to be directly related to antibody responses and to protection against challenge. The use of SRD may considerably reduce the usage of animals for potency testing of veterinary influenza vaccines. PMID- 3098606 TI - Use of the single radial immunodiffusion test as a replacement for the NIH mouse potency test for rabies vaccine. AB - The method currently recommended by the World Health Organization (WHO) for the potency assay of rabies vaccine is the NIH mouse potency test, a highly variable test requiring large numbers of animals. The Single Radial Immunodiffusion (SRID) test, an in vitro test, has been used successfully for the quantitation of hemagglutinin in inactivated influenza vaccine and is being evaluated for its utility as an assay for the rabies virus glycoprotein, considered to be the major protective antigen, of rabies vaccine. Potency values calculated using the SRID test were compared with those calculated using the NIH test for rabies vaccines produced in cell culture. The within-test variability was significantly lower with the SRID test but the potency values were generally higher than those from the NIH test. Vaccines which assay below the minimum acceptable potency value (2.5 International Units/ml) in the NIH test generally gave values above that level in the SRID test. The implications of these results on rabies vaccine control testing are discussed. PMID- 3098607 TI - Single radial immunodiffusion assays for the standardization of the antigenic content of rabies vaccines. AB - The method currently recommended for the assay of rabies vaccine potency is a mouse protection test, the NIH test. It is widely accepted that the estimates of potency obtained in such tests are imprecise. We have applied the single radial immunodiffusion (SRD) technique to the assay of the glycoprotein antigen, the major protective antigen of the rabies virion. In this paper we have summarized the results of an international collaborative study, in which SRD was shown to give reproducible estimates of glycoprotein content. In addition the use of SRD in assessing the stability of rabies vaccines is discussed. PMID- 3098608 TI - Myofibrillar protein breakdown in skeletal muscle is diminished in rats with chronic streptozocin-induced diabetes. AB - Previous reports have suggested that insulin may not regulate the breakdown of myofibrillar proteins in skeletal muscle. To further test the role of insulin, insulinopenia was produced by treating rats with streptozocin. After treatment, protein breakdown in skeletal muscle was evaluated with the isolated perfused rat hindquarter preparation. After the inhibition of protein synthesis with cycloheximide, total and myofibrillar protein breakdown were assessed by measuring the release of tyrosine and 3-methylhistidine, respectively, in the perfused hindquarters of diabetic and age-matched control rats. Streptozocin induced (65 mg/kg) diabetes (3- to 28-day duration) resulted in hyperglycemia, hypoinsulinemia, hyperphagia, increased plasma lipid levels, arrested body and muscle growth, and increased urea and 3-methylhistidine excretion. Despite this, protein breakdown in skeletal muscle diminished. The release of 3-methylhistidine by the perfused hindquarters of diabetic rats decreased, whereas the release of tyrosine remained unchanged, suggesting that the breakdown of myofibrillar proteins was affected specifically. 3-Methylhistidine (unbound) levels in skeletal muscle of unperfused diabetic rats as well as in skin decreased, whereas they increased twofold in the gastrointestinal tract. More severe diabetes (125 mg/kg streptozocin), which resulted in ketoacidosis, augmented protein breakdown in muscle; however, this response was due to a marked fall in food consumption (it was also evident when control rats were pair fed). These data reinforce previous conclusions that insulin does not play a major role in the regulation of myofibrillar protein breakdown in skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098609 TI - Oral protein hydrolysate causes liver glycogen depletion in fasted rats pretreated with glucose. AB - Studies in rats indicated that the major physiologic stimulus for synthesis of liver glycogen is a rise in the portal glucose concentration after ingestion of a meal. Conversely, glycogen degradation in the liver is stimulated by a rise in portal glucagon concentration. In humans, ingestion of carbohydrate lowers the concentration of circulating glucagon, whereas protein stimulates an increase in peripheral glucagon concentration. Little is known about the effects of these nutrients on glucagon concentrations in the rat. Therefore, we studied the effects of oral protein administration to 24-h-fasted rats pretreated with glucose for 2 h to test the effect of two potent but potentially opposite signals for glycogen metabolism. An increase in liver glycogen concentration was observed in fasted rats given oral glucose, as expected. Removal of glucose by the liver could not account for the glycogen synthesized, indicating that most glycogen formed was derived from gluconeogenesis. In addition, the apparent intracellular and extracellular glucose concentrations were not in equilibrium. A small amount of glucose may have been taken up against a concentration gradient. The portal glucagon was not significantly decreased. Oral protein administration to the rats pretreated with glucose resulted in a rapid and dramatic decrease in liver glycogen concentration. This was associated with an increase in the portal glucagon concentration, no change in insulin concentration, a slight increase in liver cAMP concentration, an increase in the active form of phosphorylase, and a decrease in the active form of synthase. Glycogenolysis could account for the glucose released into the circulation from the liver after protein administration. PMID- 3098610 TI - Interaction of cooling rate, warming rate, and extent of permeation of cryoprotectant in determining survival of isolated rat islets of Langerhans during cryopreservation. AB - Cryopreservation of islets of Langerhans offers a number of important benefits for attempts to cure diabetes by transplantation. In the published literature, a variety of cooling rates, ranging from 0.25 to 75 degrees C/min, in conjunction with warming rates of 4-200 degrees C/min have been proposed to give optimal preservation of islets. In view of the general importance of rates of temperature change in determining survival and because of the possibility of modulating tissue immunogenicity by freezing and thawing, we have studied the interaction of cooling rate and warming rate for isolated rat islets that had been either fully or partially equilibrated with 2 M dimethyl sulfoxide (DMSO). Batches of islets were stored at -196 degrees C after cooling at 0.3, 3.0, 10, 30, 60, 150, or greater than 1000 degrees C/min and then warmed at either 10 or 50 degrees C/min. Survival was assessed by measuring the secretion of insulin during static incubation in alternating nonstimulatory and stimulatory media. Cooling rates extending over three orders of magnitude proved not to be a major determinant of survival when the islets were equilibrated with 2 M DMSO: greater than 50% survival was achieved at all cooling rates studied when the warming rate was at 50 degrees C/min. Peak survival (83%) was attained at a cooling rate of 0.3 degrees C/min, but only slightly lower recoveries were obtained at 60 and greater than 1000 degrees C/min. However, in islets only partially equilibrated with cryoprotectants, functional recovery was highly dependent on the cooling and warming rates, with peak survivals after slow cooling and rapid warming. Full permeation of the tissue with cryoprotectant offered maximal recovery of function. PMID- 3098611 TI - Long-term care in Canada: a complex and intricate system. PMID- 3098612 TI - Long-term care administrators: meeting their educational needs. PMID- 3098613 TI - Examining professionals' perceptions of long-term patients in acute care. PMID- 3098615 TI - Nontraumatic rhabdomyolysis during diabetic ketoacidosis. PMID- 3098614 TI - The renal subcapsular site offers better growth conditions for transplanted mouse pancreatic islet cells than the liver or spleen. AB - In order to investigate the importance of the transplantation site for the replication of grafted islet cells, we implanted syngeneic mouse pancreatic islets intrasplenically, intraportally and subcapsularly in the kidney. Fourteen days later the alloxan-diabetic mice were killed after an injection of tritiated thymidine, and the graft-bearing organs fixed and processed for autoradiography. The highest labelling indices were recorded for subcapsularly grafted islets, followed by intraportal and intrasplenic islets in that order. In separate experiments some islet-containing kidney sections were immune stained for insulin before the autoradiographic process. The labelling index of the insulin-positive cells was as high as in the entire islet cell population of the sections from the same mice stained with haematoxylin only. This indicates that the B cells of the islets replicate as often as the other islet cell types. The present data also suggest that the renal subcapsular space offers better growth conditions for transplanted islet cells than the liver or spleen. PMID- 3098616 TI - Changes in the distribution of vinculin during preimplantation mouse development. AB - It has been proposed that vinculin is a microfilament bundle-membrane linking cytoskeletal protein. We used double-fluorescence microscopy to study the distribution of vinculin and F-actin in mouse oocytes and preimplantation embryos. In oocytes and in the cells of cleavage- and blastocyst-stage embryos, vinculin exhibited a diffuse cytoplasmic distribution and was concentrated in a submembranous layer. The presence of vinculin in oocytes was confirmed by immunoblotting. In oocytes, a distinct concentration of actin was observed above the second metaphase spindle. During the 8-cell stage, compacting blastomeres exhibited partial polarization of cortical vinculin and actin toward their outward-facing surfaces. In precompaction-stage blastomeres, the submembranous layer of vinculin contained a ring-like concentration in the most peripheral region of each intercellular contact area. During later development, the amount of vinculin localized in the areas of intercellular contacts became modified. In embryos ranging from the compacted 8-cell stage to the mid-morula stage, the vinculin-specific fluorescence was only intense in some intercellular contacts, being indistinct in most contact areas. In late morulae, the flattened outer cells increasingly exhibited concentration of vinculin in contact areas. In contrast, actin-specific fluorescence was clearly evident in most intercellular contacts throughout the morula stage. At the early blastocyst stage, all contacts of the trophectoderm (TE) cells again regularly exhibited concentration of both components. At the late blastocyst stage, the staining pattern changed once again: the contact-associated concentration of vinculin-specific fluorescence was not observed in polar TE cells, while remaining clear in mural TE cells. In blastocyst outgrowths, TE cells displayed typical vinculin plaques at the peripheries of the cells. The continuous changes in the distribution of vinculin and actin suggest that these components are involved in the control of cellular relationships during early development. Immunoelectron microscopy and experiments using cytochalasin were performed in an attempt to relate the distribution of vinculin to the ultrastructural features of embryo cells. PMID- 3098617 TI - Purine phosphoribosyltransferase (EC 2.4.2.7 and 2.4.2.8) and purine de novo synthesis activity in rat testicular tissue at different stages of development, and their correlation with the circulating levels of gonadotrophins and testosterone, and with structural changes. AB - The overall activity of the purine de novo synthesis pathway and the activities of purine phosphoribosyltransferase in the rat testis were measured at different ages and were correlated with histological observations. Similar studies of the concentration of circulating gonadotrophins and testosterone were performed. The purine phosphoribosyltransferase activities were between two and three orders of magnitude greater than purine de novo synthesis. The peak activity of the purine de novo synthesis pathway coincided with the first appearance of meiosis in the spermatocytes immediately before the luteinising hormone (LH) level rose to its peak. The highest activity of the hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8) - catalysed purine salvage pathway coincided with the first appearance of mature spermatozoa in the tubules just after the occurrence of peak levels of follicle-stimulating hormone (FSH). These findings are linked to the development of testicular atrophy in cases of severe HPRT deficiency in man. PMID- 3098618 TI - [Extreme reversible insulin resistance caused by deficiency of divalent cations during parenteral nutrition in Crohn's disease]. PMID- 3098619 TI - Limited usefulness of carbon dioxide as a contrast agent for cholangiography. AB - Carbon dioxide (CO2) was unsuccessfully used as a biliary contrast agent in 9 of 10 patients undergoing percutaneous transhepatic cholangiography prior to biliary drainage. The technique involved hand injection of 10-20 cc CO2 through the Chiba needle in an attempt to fill preferentially the anterior biliary radicals. Although CO2 remains a useful agent in many instances, particularly for percutaneous nephrostomy, its usefulness in the biliary tract is severely limited. PMID- 3098620 TI - Evidence for H+ secretion by the in vivo canine gallbladder. AB - In humans and most other species, a decline in pH of gallbladder contents occurs during the concentration of bile. Recent in vitro studies in rabbit, guinea pig, and Necturus gallbladders have strongly suggested mucosal H+ secretion during sodium reabsorption, presumably representing a Na+/H+ exchange. The present in vivo studies are the first attempt to determine whether H+ secretion by the gallbladder can be demonstrated in the living animal. Gallbladder bile was obtained from 27 anesthetized dogs after 12-24-h fasts; 12 samples of common duct bile were also obtained in 3 dogs during variable taurocholate infusion. In common duct bile, observed ranges were as follows: pH, 7.37-7.85; CO2 partial pressure (PCO2), 21-32 mmHg; total CO2 concentration ([TCO2]), 16.4-41.4 mM; total bile salt concentration ([TBS]), 16-93 mM; and [Na], 153-192 mM. In gallbladder bile, respective ranges were as follows: pH, 5.72-7.29; PCO2, 36-101 mmHg; [TCO2], 1.21-15.5 mM; [TBS], 150-305 mM; and [Na], 199-266 mM. In all samples [Na] was linearly related to [TBS]. Carbon dioxide partial pressure increased from a mean of 27.3 mmHg in common duct bile to greater than 100 mmHg in gallbladder bile at [TBS] = 180 mM, then declined to approximately 36 mmHg as [TBS] increased to greater than 300 mM. Peak PCO2 occurred at pH approximately 6.4-6.6, then declined as pH decreased to approximately 5.7. Bile to plasma PCO2 ratios increased from a mean of 1.08 in common duct samples to greater than 2.0 in gallbladder samples at pH approximately 6.3, then declined to approximately 1.0 in fully concentrated bile. If the high PCO2 values in bile were solely due to tissue CO2 production, a sustained increase in PCO2 throughout Na+ reabsorption might be expected. The results strongly suggest H+ secretion (HCO3- neutralization), as peak PCO2 occurred when [TBS] was only about 180 mM, long before sodium absorption was complete. It is hypothesized that H+ secretion may have important favorable effects on calcium lithogenicity, reducing the likelihood of the formation of CaCO3- containing gallstones. PMID- 3098621 TI - [Comparative scanning and transmission electron microscopy studies of the ependyma of the central canal in the spinal cord of primates. I. Electron optical image of the ependyma in the central canal of the spinal cord of the callithrix monkey (Callithrix jacchus, Linne 1758)]. AB - The ependyma lining the central canal of the spinal cord of adult males and females monkey, Callithrix jacchus, was examined by scanning and transmission electron microscopy. The cross section of the lumen of the central canal are round, oval, or triangular. Light and dark ependymal cells, depending on the density of the cytoplasm, were found. The light ependymal cells are fewer than the dark cells. The ependyma cytoplasm contained numerous mitochondria, filamentous structures, one or more well-developed Golgi-complexes, vesicles of the smooth endoplasmic reticulum, ribosomes, lysosomes, multivesicular bodies, profiles of the rough endoplasmic reticulum, large osmophilic bodies, and microtubules. The nuclei of the ependyma cells usually have a simple, regular round or oval shape. They occupy a relatively large portion of the cell volume and lie in the central or mediobasal position. Some of the nuclei show deep invaginations into the karyoplasm. Most of the mitochondria occupy mainly the supranuclear portion of the apical cytoplasm. There are of the crista-typ. Ribosomes occur free in the cytoplasm, but some attached to the profiles of the rough endoplasmic reticulum or being arranged as polysomes. The filamentous structures are generally prominent cytoplasmic components and are distributed at the apical, lateral, or basal region of the ependymocytes. They are grouped into bundles and arranged in parallel arrays. Some of these bundles reach the plasmamembrane at the free lumina of the central canal, others take contact to the filamentous structures of the zonulae adherentes of the junctional complex below the free surface. The granular endoplasmic reticulum shows specializations. There profiles surrounding granular substances and widely distributed granulations in connection with the nuclear envelope. The functional significance of the deposition of these granulations is still unknown. The luminal surface of the ependymocytes bears many microvilli and cilia. The cilia are regularly arranged in cranio-caudal direction. Each cilium has the typical (9 + 2) subfibres. The intercellular space at the surface of the ependymal layer shows a single zonula adherens or zonulae adherentes in the row. Tight junctions and gap junctions were not found in the material examined. Cell processes of liquor contacting neurons between adjacent ependyma cells, protruding into the lumen of the central canal, could be observed. The termination of these neurons contains accumulations of mitochondria in the central part, large amounts of vesicles, and small dense bodies. They have short microvilli and some stereocilia at the free surface.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3098622 TI - [Effect of lithium carbonate on the experimental post-radiation recovery of the blood system]. PMID- 3098623 TI - Studies of normal and position-affected expression of rosy region genes in Drosophila melanogaster. AB - Transformant complementation, intragenic deletions and Northern blot analyses provide unambiguous localization of the l(3)S12 gene immediately proximal to the 5' end of the rosy locus. We have characterized an array of transformants with respect to l(3)S12 and rosy expression. The l(3)S12 gene is exceedingly sensitive to euchromatic site-specific position effects. Unlike the rosy locus, l(3)S12 is insensitive to heterochromatic position effect in rearrangements, as well as in a transformant located in heterochromatin. Cotransformants for both l(3)S12 and rosy elicit no apparent pattern of concordance with respect to euchromatic site specific position effects. Heterochromatic-euchromatic rearrangements are examined with respect to position effects on expression of the rosy region genes l(3)12, rosy, snake and piccolo, as well as suppressor effects. Clear distinction is seen between euchromatic and heterochromatic effects. PMID- 3098624 TI - Magnification of the ribosomal genes in female Drosophila melanogaster. AB - The genetically induced increase in the number of 18S + 28S ribosomal genes known as magnification has been reported to occur in male Drosophila but has not previously been observed in females. We now report that bobbed magnified (bbm) is recovered in progeny of female Drosophila carrying three different X bobbed (Xbb) chromosomes and the helper XYbb chromosome, which is a derivative of the Ybb- chromosome. Using different combinations of bb or bb+ X and Y chromosomes, we show that magnification in females requires both a deficiency in ribosomal genes and the presence of a Y chromosome: X/X females that are rDNA-deficient but do not carry a Y chromosome do not produce bbm; similarly, X/X/Y females that carry a Y chromosome but are not rDNA-deficient do not produce bbm. Bobbed magnified is only recovered from rDNA-deficient X/XY, X/X/Y or XX/Y females. We have also found that females carrying a ring Xbb chromosome together with the XYbb- chromosome do not produce bbm, indicating that ring X chromosomes are inhibited to magnify in females as in males. We postulate that the requirement for a Y chromosome is due to sequences on the Y chromosome that regulate or encode factor(s) required for magnification, or alternatively, affect pairing of the ribosomal genes.--These studies demonstrate that magnification is not limited to males but also occurs in females. Magnification in females is induced by rDNA deficient conditions and the presence of a Y chromosome, and probably occurs by a mechanism similar to that in males. PMID- 3098625 TI - The genetic factors altered in homozygous abo stocks of Drosophila melanogaster. AB - Females homozygous for the maternal-effect mutation abo (2-44.0) produce a large fraction of eggs which arrest during embryogenesis. Increasing doses of defined heterochromatic regions inherited by offspring of abo mothers from their fathers function zygotically to bring about a partial rescue of the abo-induced embryonic lethality. Another property of the abo mutation is that the severity of the maternal effect decreases when an abo stock is maintained in homozygous condition for a number of generations. Here, we show that the factors which change in homozygous abo stocks to result in the decrease in maternally induced embryonic lethality, act zygotically, dominantly and additively. More importantly, we show that the X and second chromosomes, but not the Y and third chromosomes, derived from homozygous abo stocks are, when inherited from males, more effective in promoting zygotic rescue of the abo-induced lethality than are the equivalent chromosomes derived from an abo stock maintained in heterozygous condition. The chromosomal locations of the factors maintained in the homozygous condition. The chromosomal locations of the factors altered in homozygous stock, as well as their behavior, strongly suggest that the same heterochromatic elements that are responsible for rescuing embryos from the abo-induced maternal effect are altered in homozygous abo flies in such a way that the maternal effect itself is less severe. PMID- 3098626 TI - Gonadal dysgenesis determinants in a natural population of Drosophila melanogaster. AB - Three populations of Drosophila melanogaster from northern California were surveyed for the ability to produce and resist gonadal dysgenesis in the P-M system of hybrid dysgenesis. Males from all three populations produced low to moderate levels of gonadal dysgenesis in crosses to Oregon-R M females. Most females had the P cytotype, but the M cytotype occurred occasionally. The three populations could not be statistically differentiated from one another, but were easily distinguished from populations from Australia and Wisconsin on the basis of gonadal dysgenesis potential. The California populations had higher levels of M cytotype than did the Wisconsin population. Thirteen X chromosomes and 11 pairs of autosomes were extracted from one of the California populations, using a modification of the standard balancer chromosome technique to suppress hybrid dysgenesis during extraction. All lines produced strongly skewed sterility distributions in crosses to M-strain females, and mean levels of sterility were less than 50%. There was evidence of nonadditive interactions between the autosomes. Most extraction lines had the P cytotype, but M and intermediate cytotypes were observed. Some of the intermediate cytotypes were stable over time. Lines were tested at two different times after extraction. Some lines evolved higher sterility potential as they were kept in the laboratory, even in the presence of P cytotype. The results point out a number of deficiencies in current genetic and population genetic models of hybrid dysgenesis and imply that gonadal dysgenesis is unlikely to be an important evolutionary force in this population. PMID- 3098627 TI - The relationship between the functional complexity and the molecular organization of the Antennapedia locus of Drosophila melanogaster. AB - The Antp locus is involved in the development of the thorax of the larval and adult Drosophila. The absence of Antp+ function during embryogenesis results in the larval mesothorax exhibiting characteristics of the prothorax and an ensuing lethality; the loss of Antp+ function in the development of the adult thorax causes specific portions of the leg, wing and humeral imaginal discs to develop abnormally. Every Antp mutation, however, does not cause all of these developmental defects. Certain mutant alleles disrupt humeral and wing disc development without affecting leg development, and they are not deficient for the wild-type function required during embryogenesis. Other Antp mutations result in abnormal legs, but do not alter dorsal thoracic development. Mutations of each type can complement to produce a normal adult fly, which suggests that there are at least two discrete functional units within the locus. This hypothesis is supported by the fact that each of the developmental defects arises from the alteration of a different physical region within the Antp DNA. These observations indicate that the complete developmental role of the Antp locus is defined by the spatial and temporal regulation of the expression of several individual functional units. PMID- 3098628 TI - Several galactosyltransferase activities are associated with mouse chromosome 17. AB - Indirect evidence suggests that some major histocompatibility complex (MHC) proteins are glycosyltransferases. No sequence or mapping information is available for transferases, although ganglioside variations in mice are linked to the H-2 complex on chromosome 17, and one galactosyltransferase activity on mouse sperm varies with T/t complex genotypes, also on chromosome 17. In the present experiments, diploid and trisomy 17 mouse embryos were assayed for four different galactosyltransferase activities. The same preparations were assayed for isocitrate dehydrogenase (Id-1, chromosome 1) and glyoxalase-1 (Glo-1, chromosome 17). Galactosyltransferase specific activities in trisomy 17 embryos are almost 1.5 times higher than in diploid embryos. The correlation between galactosyltransferase activities and chromosome 17 dosage indicates that the structural or regulatory gene for these enzymes are located on chromosome 17. PMID- 3098630 TI - [Mitomycin C-induced mutagenesis]. AB - The mutagenic effect of mitomycin C (MC) has been shown in the S phase of Crepic capillaris cells. The repair ability of MC-induced DNA lesions proves exceedingly high, due to post-replicative and excision repair processes. In the experiments with MC-pretreatment of Crepic capillaris cells, nonmutagenic concentration of 1 microgram/ml provides inducible repair system--"adaptive response", which considerably decreases the levels of mutagenesis induced by MC at concentrations of 10, 20 and 40 micrograms/ml. Under adaptive response, the action of methyltransferase is possible. PMID- 3098629 TI - [Formation of heat-sensitivity in the ontogenesis of a heat-resistant Drosophila strain and the relation between this property and the mutation process]. AB - In the experiments with a heat-resistant line of Drosophila melanogaster, it has been shown that organismal heat-resistance is formed during ontogenesis, prior to hatching, though it can be changed, in accordance with the temperature conditions after hatching (acclimation). Heat-resistance of germ cells is formed during the pupal stage; it depends on the development temperature and remains unchanged thereafter. The mutation rate (the frequency of dominant lethals) in oocytes depends on the development temperature and not on the temperature life conditions of imago. Therefore, it may be concluded that heat-resistance of germ cells as well as their reaction on extreme temperatures are autonomous, meaning their independence of this property in the organism. PMID- 3098631 TI - [Survival of Pseudomonas aeruginosa in the hospital environment]. PMID- 3098632 TI - Negative bias in estimates of the correlation between children's weight-for height and height-for-age. AB - Several analyses of cross-sectional anthropometric survey data have found weak correlations between children's weight-for-height and height-for-age. Random non sampling error in height measurement can produce a significant negative bias in estimates of their correlation. The size of this bias is quantified here using Monte Carlo simulation techniques. Even when two-thirds of height measurements are within two centimeters of their true value, the median estimate of the correlation is .095 below its true value for the sample. There may be differences in the etiology of protein energy malnutrition, as represented by stunting (low height-for-age) and wasting (low weight-for-height), but inferences based on cross-sectional data alone may be misleading, unless random measurement error is negligeable. PMID- 3098633 TI - Postnatal development of disaccharidase activities in jejunal fluid of preterm neonates. AB - Because human fetuses of 26-30 weeks gestation are known to have low levels of intestinal mucosal lactase activity, it has been assumed that live born preterm neonates of comparable gestational age are also lactase deficient. We have previously shown that disaccharidase activities in jejunal fluid in infants are highly significantly correlated with enzyme activities in the adjacent mucosa. We have now measured disaccharidase activities cross-sectionally and longitudinally in the jejunal fluid of a group of very preterm neonates of 26-29 weeks gestation who were fed with pasteurised human milk. Lactase activity was within the normal range for older infants and children within the first week of life. Sucrase: lactase ratios fell significantly in the second and third weeks of life, strongly suggesting a further increase in lactase activity. This increase was independent of postconceptional age. Preterm neonates are not as lactase deficient as previously believed, and this has implications in the search for optimal feeding regimes. PMID- 3098635 TI - Topics and controversies in enteral nutrition. Proceedings of the Seventh Nutricia International Symposium. PMID- 3098634 TI - Effect of binding of ionised calcium on the in vitro nucleation of cholesterol and calcium bilirubinate in human gall bladder bile. AB - Biliary calcium may be a nucleating agent in cholesterol cholelithiasis. A study was designed to determine the effect of binding of ionised calcium on in vitro nucleation time. Ultracentrifuged and microscopically clear gall bladder bile from cholesterol gall stone patients was divided into two aliquots. One aliquot served as control and ionised calcium was bound in the second aliquot by addition of EDTA. Nucleation time was observed for the two groups. Addition of EDTA had no effect on lipid composition of the biles. EDTA bound all ionised calcium. Calcium bilirubinate precipitated from all controls on day 1 but was absent in all samples with EDTA. Addition of EDTA had no effect on cholesterol crystal nucleation time; nucleation time was rapid in both the controls and samples with EDTA. Ionised calcium is essential for calcium bilirubinate precipitation but is not responsible for the rapid nucleation time of bile from cholesterol gall stone patients. PMID- 3098636 TI - Branched chain amino acids in liver disease: fact or fantasy? PMID- 3098637 TI - Future of enteral nutrition. AB - Although there has been agreement that enteral nutrition remains an excellent means of providing nutritional support to malnourished patients with normal or near normal gastrointestinal function, it is clear that areas of controversy do exist, and attention needs to be directed towards these in the future. PMID- 3098638 TI - Indications for nutritional support. AB - In this review different types of patients who usually require nutritional support are considered and recommendations made as to when nutritional support should be started, how long it should be continued, and which substrates should be preferentially used by which route. PMID- 3098639 TI - Some psychological and physiological aspects of enteral nutrition. AB - This review discusses three main topics: the first relates to the effects of underlying disease, malnutrition, and nutritional support on appetite; the second is concerned with the role of enteral feeding in short bowel syndrome; and the third deals with the clinical benefits of enteral nutrition. PMID- 3098640 TI - Diet formulation and choice of enteral diet. PMID- 3098641 TI - Enteral feeding: techniques of administration. PMID- 3098642 TI - Complications of enteral nutrition. AB - Complications may arise during enteral feeding that are usually related to the diameter and rigidity of the tube or the delivery, composition, and sterility of the feed uses. By using a soft, fine bore tube to deliver a sterile feed of known composition, by continuous infusion rather than as a bolus, most of these complications can be avoided. PMID- 3098643 TI - Bacterial contamination of enteral diets. AB - Enteral feeding solutions can be contaminated by bacterial micro-organisms already present in the ingredients, or introduced during preparation or transport, or in the hospital ward. During jejunostomy feeding without pump or filter, ascending bacterial invasion of the feeding bag is possible. In patients with lowered immune response contaminated feedings can cause serious septic clinical problems. The progressive loss of the nutritional value of the enteral feeding solution by bacterial contamination has to be considered for all patients. PMID- 3098644 TI - Role of dietitians in enteral feeding. AB - Awareness of the nutritional requirements of inpatients has been sadly neglected for many years. Students in British medical schools are taught little about clinical nutrition and the role of the dietitian. Dietitians, on the other hand, spend four years learning the science of nutrition and dietetics. In most hospitals in Britain dietitians are responsible for giving advice on a wide range of therapeutic diets, and only a minority specialize in one particular aspect of nutrition and dietetics. Recent changes and developments in nutritional support have offered an exciting and interesting challenge to dietitians, who with their well established background in nutrition, can play an important part in the nutritional care team. PMID- 3098646 TI - Enteral nutrition in inflammatory bowel disease. AB - To assess the effect of the addition of enteral tube feeding with polymeric diets to the standard treatment of acute attacks of inflammatory bowel disease a total of 43 patients admitted to hospital (23 with Crohn's disease and 20 with ulcerative colitis) were studied retrospectively. Total enteral nutrition was given to 26 as the sole nutritional supply and to 17 in conjunction with a normal ward diet, when appropriate, according to the severity of attack (control group). Nutritional state was assessed and classified in all patients at admission and at the end of the study, by measuring the triceps skinfold thickness, mid arm muscle circumference, and serum albumin concentration as representative of body fat, muscle protein, and visceral protein, respectively. At admission the three nutritional variables were not statistically different between the groups. There was a significantly positive effect on mid arm muscle circumference in patients on total enteral nutrition compared with the control group, but there was no effect on either triceps skinfold thickness or serum albumin concentration. The percentage of subjects requiring intravenous albumin infusion, however, was significantly less in the group fed enterally than in the control group. In addition, fewer patients in the group fed enterally required surgical treatment compared with the control group, despite the fact that one of the criteria for starting enteral nutritional support was the expectancy that surgery would be needed. Total enteral nutrition was well tolerated and no major side effects arose during its use in patients with acute exacerbations of inflammatory bowel disease. PMID- 3098645 TI - Role of nutrition in inflammatory bowel disease: an overview. AB - Although many patients with inflammatory bowel disease are malnourished, the role of nutritional support is still controversial. It is universally accepted that with adequate nutritional support patients will put on weight and that their biochemical functions may improve; the question nevertheless remains: does this help the patient get over his or her disease more quickly and, more importantly, does this affect morbidity and mortality? There are several ways of providing nutritional support and all need careful evaluation. PMID- 3098647 TI - Parenteral nutrition in inflammatory bowel disease. AB - Nutritional support, administered via the enteral or parenteral routes, has been widely introduced in the treatment of inflammatory bowel disease over the past decade. The precise place of total parenteral nutrition, however, as a sole or adjunct treatment of inflammatory bowel disease, has yet to be defined. PMID- 3098649 TI - Metabolic response to malnutrition: its relevance to enteral feeding. AB - Malnutrition results in a wide variety of metabolic responses, depending on circumstances, from reactions to pure deprivation of nutrients to include the added stress of injury and sepsis. Important differences of response exist between adults and children. Weight loss with changes in carbohydrate, fat, and protein metabolism are well documented. Disturbances of fluid and electrolyte balance are newer areas of interest as are changes in requirements for micronutrients such as trace metals. Many of these metabolic changes are under hormonal control. The intestinal tract shares in the response to malnutrition, and the consequent changes in mucosal function determine the ability of the intestine to handle enteral feeds. Such a route for nutritional support is important in protecting intestinal function not only in absorption but also in hormone production. Enteral feeding is increasingly having an important role in the interactions between acute diarrhoeal disease and malnutrition. PMID- 3098648 TI - Nutritional support: how much for how much? AB - Although malnutrition is associated with poor clinical outcome, it cannot be inferred that better nutrition will improve clinical outcome. Efficacy of a proposed regimen is best established by prospective, randomised, controlled trials. Cost effectiveness is only an issue if efficacy exists. Patients with long term temporary, or permanent, inadequate bowel syndrome are candidates for parenteral nutrition. Most of the prospective, randomised, controlled trials testing the value of nutritional support in other diseases, however, have failed to show that this treatment has a beneficial clinical effect. Areas where these trials have shown a possible clinical benefit include the perioperative care of patients with upper gastrointestinal cancer, elemental diet treatment of Crohn's disease, and branched chain amino acid infusions in hepatic encephalopathy. Even in these instances, it is not clear that such treatment will prove to be cost effective (compared with other currently available treatments). PMID- 3098650 TI - [Evaluation of therapeutic plasmapheresis]. PMID- 3098651 TI - [Ambulatory hysteroscopy]. PMID- 3098652 TI - [Acquired immunodeficiency in a patient with hemophilia]. PMID- 3098654 TI - [Pharmacological studies on ginger. IV. Effect of (6)-shogaol on the arachidonic cascade]. AB - (6)-Shogaol, a pungent component of ginger, which is contained in semi-dried ginger but is rarely found in fresh ginger inhibited carrageenin-induced swelling of hind paw in rats and arachidonic acid (AA)-induced platelet aggregation in rabbits. Moreover, (6)-shogaol prevented prostaglandin I2 (PGI2) release from the aorta of rats when tested as an inhibitor of platelet aggregation. These results suggest that (6)-shogaol may have an inhibitory action on the cyclo-oxygenases in both platelets and aorta. Examination of the effects of (6)-shogaol on cyclo oxygenases in rabbit platelets and microsome fractions of rat aorta indicated that (6)-shogaol inhibited cyclo-oxygenase activities of both tissues in a concentration-dependent manner. Furthermore, when we examined the effect of (6) shogaol on 5-lipoxygenase from RBL-1 cells, (6)-shogaol exhibited an inhibitory action on 5-lipoxygenase activity. Therefore, it seems that the inhibitory effects of (6)-shogaol on the carrageenin-induced paw edema, AA-induced platelet aggregation and PGI2 production of aorta may be caused by the inhibition of cyclo oxygenase activity. PMID- 3098655 TI - The adhesin structures involved in the adherence of group B streptococci to human vaginal cells. AB - The adherence of group B streptococci (GBS) of serotypes Ia, II and III to human vaginal cells was studied in vitro. The adherence was not dependent on the viability of bacteria; killing of GBS by UV irradiation or glutaraldehyde treatment did not inhibit the adherence. Killing of GBS by heating to 56 degrees C for 1 h led to a pronounced decrease of adherence, demonstrating the thermosensitivity of the GBS structures involved. The protein nature of these structures was proved by a significant reduction of adherence after pretreatment of GBS with trypsin or pepsin. Pretreatment of GBS with sialidase had no influence on the adherence. Such a pretreatment of vaginal cells caused an increase of adherence showing that the receptors on epithelial cells may be partly masked by sialic acid. PMID- 3098653 TI - [Pharmacological studies on proglumetacin maleate, a new non-steroidal anti inflammatory drug. (3) Damaging effects on the gastrointestinal tract]. AB - Damaging effects on the gastrointestinal tract of proglumetacin maleate (PGM), a new indomethacin (IND) derivative, were examined in comparison with those of IND. Gastric and small intestinal lesions were maximum 4 and 24 hr after a single oral administration of PGM, respectively. Ulcerogenic effects of PGM on the gastric mucosa were approximately 1/7 and 1/10 times as potent as those of IND on a molar ratio 4 hr after single oral dosing to fasting and feeding rats, respectively. PGM was also less active on the small intestinal mucosa 24 hr after single oral dosing. After repeated dosing for 7 days, ulcerogenic effects of PGM were about 1/3 and 1/2 times more potent than those of IND on the gastric and the small intestinal mucosa, respectively. The weak ulcerogenicity of PGM appears to be due to the fact that it has little direct action on the gastrointestinal mucosa. On the other hand, protective effects of PGM on diarrhea induced by arachidonic acid in mice were about 1/2 times as potent as those of IND in both 1 and 4 hr pretreatments. So PGM must have less inhibitory effects on prostaglandin biosynthesis in the intestine than IND. PGM is a safer drug than IND because it has less damaging effect on the gastrointestinal mucosa. Therefore, it may be much more useful for the treatment of chronic inflammatory disorders like rheumatoid arthritis. PMID- 3098656 TI - [Peripheral retinal dystrophy following administration of canthaxanthin?]. PMID- 3098657 TI - International health care spending. PMID- 3098658 TI - National medical care spending. PMID- 3098660 TI - Protecting the elderly against high health care costs. PMID- 3098659 TI - The challenge of 'real' competition in Medicare. PMID- 3098661 TI - Uncovering the high costs of teaching hospitals. PMID- 3098662 TI - High expectations versus limited resources. PMID- 3098663 TI - Monoamine oxidase in bovine thyroid tissue. AB - Two functional forms of monoamine oxidase (MAO) defined as MAO A and MAO B have been described in several tissues. In this study the characteristics of MAO present in a particulate subcellular fraction of bovine thyroid tissue were investigated. The selective inhibitors of MAO, clorgyline (A form) and deprenyl (B form) were used. The monoamines 5-hydroxytryptamine (5-HT) (preferred of the A form), tyramine (both forms) and beta-phenylethylamine (PEA) (B Form) were used as substrates. MAO activity towards 5-HT was markedly inhibited by clorgyline. Tyramine oxidation was very sensitive to clorgyline and the curve obtained was in accordance with the presence of a high proportion of the A form. MAO activity towards PEA was also markedly inhibited by clorgyline. Deprenyl was not able to induce modifications in the MAO activity except when it was used at very high concentrations. According to these results the bovine thyroid tissue contains predominantly the A form of MAO. In this tissue PEA was deaminated by the A form of the enzyme. PMID- 3098664 TI - Orthotopic liver transplantation for type I Crigler-Najjar syndrome. AB - A neurologically normal 3-year-old girl with Type I Crigler-Najjar syndrome was successfully treated with orthotopic liver transplantation. Preoperative serum bilirubin concentrations as high as 31 mg per dl were not diminished with phenobarbital or phototherapy. Bilirubin fractionation of duodenal bile prior to transplantation revealed 87.1% unconjugated bilirubin and 12.9% monoconjugates as determined by alkaline methanolysis-high-performance liquid chromatography. Postoperatively, the serum bilirubin concentration quickly fell to normal. Uridine diphosphate glucuronyl transferase activity in the recipient liver was not detectable. The gallbladder bile bilirubin concentration of 23.9 mg per dl was less than 15% of previously reported normal values. Since devastating kernicteric brain injury is the invariable outcome of Type I Crigler-Najjar syndrome, liver transplantation should be performed when phototherapy cannot maintain the serum bilirubin concentration at an unequivocally safe level. PMID- 3098666 TI - Characterization of the molecular forms of fibronectin in fulminant hepatic failure. AB - The plasma levels of the opsonic glycoprotein fibronectin are decreased in patients with fulminant hepatic failure, which may be an important factor in their impaired host-defense. Twenty-nine patients in fulminant hepatic failure were studied on admission, and the mean fibronectin level in Grade 0-2 encephalopathy was 82 micrograms per ml (range = 0 to 150) and in Grade 3-4 encephalopathy 61 micrograms per ml (range = 5 to 158) as compared to normal controls (268 micrograms per ml, range = 178 to 380, n = 62). No fibronectin degradation products could be detected in fulminant hepatic failure plasma by sodium dodecyl sulfate-gel electrophoresis on a polyacrylamide gradient (5 to 15%) followed by immunoblotting onto nitrocellulose with detection using a rabbit antihuman fibronectin antiserum visualized with a peroxidase conjugate. The plasma levels of the marker proteolytic enzyme cathepsin D were significantly elevated in fulminant hepatic failure (120 +/- 31 mU per ml per hr) as compared to the normal controls (18 +/- 2.1 mU per ml per hr, n = 10, p less than 0.01). Cross-immunoelectrophoresis of fulminant hepatic failure plasma for fibronectin on agarose plates gave an additional slower migrating peak in 15 of the 29 patients, as well as that of fibronectin, which corresponded to the fibronectin complex reported by other workers in leukemia. An intermediate gel containing antihuman fibrinogen demonstrated fibrinogen to be one component of this complex. Binding of other substances to fibronectin will reduce its apparent biological activity and may be the result of their lack of clearance by the damaged liver. PMID- 3098665 TI - Further studies by immunofluorescence of the monoclonal antibodies associated with experimental non-A, non-B hepatitis in chimpanzees and their relation to D hepatitis. AB - To further investigate the specificity of the monoclonal antibodies (48-1 and S 1) associated with non-A, non-B hepatitis, extensive immunofluorescence studies were performed on liver biopsy specimens from chimpanzees with experimental hepatitis A, B, non-A, non-B or delta, or from normal chimpanzees. Both 48-1 and S-1 antibodies reacted in the same manner with liver biopsy specimens from 47 of 50 (94%) chimpanzees with acute or chronic non-A, non-B hepatitis and 15 of 18 (83%) chimpanzees with type D hepatitis. Examinations of serial liver biopsy specimens revealed that the duration of expression of the antigen reacting with the antibodies in hepatocytes of chimpanzees infected with non-A, non-B viruses appeared to be longer than that of chimpanzees infected with the hepatitis delta virus. By thin-section electron microscopy, the presence of the microtubular aggregates, identical to those previously described for chimpanzees with non-A, non-B hepatitis and shown by immunoelectron microscopy to react with the antibodies, was noted in hepatocytes during the acute phase of hepatitis delta virus. The antibodies did not react with liver biopsy specimens from chimpanzees acutely or chronically infected with hepatitis B virus or hepatitis A virus, or from normal chimpanzees. The present results confirm our previous observations with the 48-1 and S-1 antibodies. Furthermore, the finding that these two antibodies were also associated with hepatitis D would support the possibility that non-A, non-B agents and the hepatitis delta-virus may have a similar nature or may elicit a similar host response. PMID- 3098668 TI - Data systems set to measure rehab effectiveness. PMID- 3098667 TI - Apolipoprotein AI and alcoholic liver disease. AB - A prospective study of apolipoprotein AI has been undertaken in 581 alcoholic patients and in 100 controls in order to describe the changes of apolipoprotein AI according to the different stages of the alcoholic liver disease, to correlate the changes to serum liver tests and to estimate its diagnosis and prognostic value. Results showed that apolipoprotein AI concentration is highly related to the degree of liver injury, reaching a maximum in patients with steatosis (229 +/ 90 mg per dl), beginning to decrease in patients with fibrosis (188 +/- 88 mg per dl) and reaching a minimum in patients with severe cirrhosis (91 +/- 46 mg per dl). Apolipoprotein AI had an independent and discriminative value for the diagnosis of fibrosis (p less than 0.001) vs. steatosis and for the diagnosis of cirrhotic vs. noncirrhotic fibrosis (p less than 0.001) or vs. acute alcoholic hepatitis without cirrhosis (p less than 0.001). Cirrhotic patients with apolipoprotein AI less than 100 mg per dl had a lower survival rate at 1 year (62 +/- 7%) than patients with greater value (80 +/- 6%; p less than 0.05), but this prognostic value disappeared in multivariate analysis when other known prognostic factors were taken into account. PMID- 3098669 TI - Will subacute care fall under PPS in 1987? PMID- 3098670 TI - Physician payment plan sparks nationwide uproar. PMID- 3098671 TI - DRG payments for RAPs slated in '87. PMID- 3098672 TI - Cell culture studies on neurofibromatosis (von Recklinghausen). V. Monosomy 22 and other chromosomal anomalies in cultures from peripheral neurofibromas. AB - Cell cultures grown from peripheral neurofibromas of three patients suffering from sporadic peripheral neurofibromatosis (NF) were analysed cytogenetically at early in vitro passages. The NF-cultures exhibited a 6.7-fold higher frequency of aneuploid mitoses, including pseudodiploids, than the control cultures derived from the skin of three healthy donors. The predominant numerical anomaly was monosomy 22. Several, as yet unidentified marker chromosomes occurred in the NF cultures, which also showed a much higher level of unstable chromosomal anomalies. The role of monosomy 22 in tumorigenesis of meningiomas and neurofibromas is discussed. PMID- 3098673 TI - Gene differentiation in four subcastes of Brahmins from Visakhapatnam, Andhra Pradesh. AB - Blood group (ABO, MN, Rh, CcDEe) polymorphisms are reported here for 4 strictly endogamous subcastes of Andhra Brahmins. The coefficient of gene differentiation calculated from the gene frequencies is 0.87% demonstrating that only a small fraction of the total gene diversity is attributable to the differences between subcastes. In spite of the strict endogamy for the past 10-14 centuries, 99.13% of gene differentiation exists within the subcastes. PMID- 3098674 TI - Bridging the research gap between acute and long-term care of older adults. PMID- 3098675 TI - Fluorescence labelling of biologically important molecules. PMID- 3098676 TI - Activation of macrophages to inhibit proliferation of Mycobacterium tuberculosis: comparison of the effects of recombinant gamma-interferon on human monocytes and murine peritoneal macrophages. AB - When cultured in 20% heat-inactivated human serum, human monocytes from seven donors were not on average significantly different from non-activated murine peritoneal cells (cultured simultaneously and in an identical manner) in their ability to inhibit BCG and, when calculated relative to growth of bacilli in the same medium without macrophages, to enhance the growth of Mycobacterium tuberculosis. Recombinant gamma-interferon caused marked inhibition of virulent M. tuberculosis by murine (BALB/c) peritoneal macrophages. This effect was seen, whether the cells were cultured in 10% fetal calf serum or in 20% heat inactivated normal human serum, with or without the addition of iron supplements. However, unlike murine cells, the addition of crude lymphokine or recombinant gamma-interferon to human monocytes caused only weak inhibition of M. tuberculosis, and in some instances, gamma-interferon caused enhancement of growth of the bacilli. Monocytes were only slightly more effective if precultured for 4-8 days before the addition of the activating stimulus. This relative failure to develop anti-mycobacterial mechanisms occurred in spite of the activation of the cells as shown by a massive increase in reduction of nitro-blue tetrazolium inducible by phorbol myristate acetate. PMID- 3098678 TI - The capacity of lymphokine production by peripheral blood lymphocytes from aged humans. AB - The functional capability to produce interleukin 2 (IL2) and interferon gamma (IFN gamma) by peripheral blood lymphocytes (PBL) from elderly humans was evaluated. Thirty-nine samples of PBL derived from donors aged from 56 to 79 yr were cultured with phytohaemagglutinin (PHA) as stimulus at 37 degrees C for 48 hours. The IL2 activity in the supernatants was measured by its ability to sustain the IL2-dependent CTLL growth. Cultures of elder human T cells produced low level of IL2 activity, that is on the average of 9.7 +/- 9.8 mu/ml, equivalent to 28.1% the IL2 activity in parallel cultures of PBL derived from young donors (34.2 +/- 8.3 mu/ml, assessed on the basis of 145 samples). In the elder humans, the IL2 production by PBL decreased progressively as the increase of the age of the donors. In contrast to the impairment of IL2 production, the amount of IFN gamma secretion by elder human T cells was almost at the same level as that by young human T cells. The average IFN gamma activity of 39 samples of elder PBL cultures and 128 samples of young PBL cultures was 2,961 +/- 736 mu/ml and 3133 +/- 950 mu/ml, respectively. There was no significantly positive correlation between the level of IL2 and IFN gamma when comparison was made based on each individual samples. This implies that it may exist an alternative way of IFN gamma production which does not require the induction by IL2, and the relatively high level of IFN gamma may not impose adverse effect on the IL2 production. PMID- 3098677 TI - Functional characterization of Con A-responsive Lyt2-positive mouse small intestinal intraepithelial lymphocytes. AB - The surface phenotypes of resting vs Con A-stimulated intraepithelial lymphocytes (IEL) from mouse small intestine were directly determined by immunofluorescence with double labelling. Both Thy 1.2+, Lyt 2+ and Thy 1.2+ Lyt 2- IEL underwent blastogenesis and expressed interleukin-2 (IL-2) receptors. The Lyt 2+ subsets of IEL (which represent 80% of the total cells) were isolated by panning and shown to proliferate in response to Con A and IL-2, although the frequency of responsive precursors was dramatically lower than that seen in the splenic Lyt 2+ T-cell population (1 in 500 vs 1 in 8, respectively). Con A-stimulated Lyt 2+ IEL produced lymphokines supporting the growth of the interleukin-3 (IL-3)-dependent cell line DA-1, and of the FDC-P2 cell line that proliferates in response to both IL-3 and GM-CSF. The results therefore support the possibility that Lyt 2+ IEL act as inducers of local cell-mediated immune reactions by producing haematopoietic lymphokines. PMID- 3098679 TI - Formation of a cyclic adenine adduct with a 4-nitroquinoline N-oxide metabolite model. AB - Pentacyclic adducts are obtained in the reaction of adenine derivatives with the diacetyl ester of 4-hydroxyamino quinoline oxide, the postulated metabolite of the potent carcinogen, 4-nitroquinoline N-oxide (4-NQO). PMID- 3098681 TI - Thrombin-induced calcium-independent degranulation of human neutrophils. AB - Thrombin, a highly specific coagulation factor, can rapidly trigger lysozyme release from human neutrophils without concomitant activation of the 5 lipoxygenase pathway. This activation was not dependent on the presence of extracellular calcium. Since thrombin also induces the release of hemostatic and inflammatory metabolites from platelets and mast cells, it is proposed that it plays a significant role in amplification of the inflammatory response. PMID- 3098680 TI - Protamine sulfate-induced enzyme secretion from rabbit neutrophils. AB - Protamine sulfate induces enzyme secretion from rabbit neutrophils. Enzyme secretion is mainly due to exocytosis but, depending on the experimental conditions, a small amount of cytolysis may occur. As compared with stimulation of neutrophil functions by other activators, protamine sulfate-induced enzyme release by exocytosis is a relatively slow process and is not accompanied by a marked activation of the metabolic burst. For optimal exocytosis, extracellular Ca2+ is required, but there is still some enzyme release in its absence, and other metal ions (Sr2+, Ba2+, Mg2+) can partly mimic the effect of Ca2+. Positive charges on protamine are of primary importance because the polyanion heparin completely inhibits protamine sulfate-induced enzyme release. Protamine linked to agarose beads is able to induce enzyme release; thus the induction of exocytosis is due to an interaction of the positive charges on protamine with the plasma membrane. Sialic acid residues on the membrane, however, seem not to play an important role in this process. PMID- 3098682 TI - Wolman's disease. PMID- 3098684 TI - Sialic acid of group B Neisseria meningitidis regulates alternative complement pathway activation. AB - The effect of meningococcal cell-associated sialic acid on activation of the human alternative complement pathway was examined by using a quantitative fluorescence immunoassay to assess alternative pathway-mediated C3 binding to a group B strain of Neisseria meningitidis from which graded amounts of sialic acid had been removed with neuraminidase. Using human serum absorbed with strain B16B6 (B:2a:L2,3) and chelated with 10 mM MgCl2 and 10 mM ethylene glycol-bis(beta aminoethyl ether)-N,N,N',N'-tetraacetic acid, we found an increase in the amount of C3 bound by enzymatically desialylated B16B6 organisms over the amount bound by fully sialylated organisms. This increase was proportional to the amount of sialic acid cleaved from the bacteria. Enhanced C3 binding was accompanied by an increase in factor B deposition. A sialic acid-deficient mutant of strain B16B6, designated 2T4-1, bound C3 via the alternative pathway at a level equivalent to that bound by wild-type meningococci from which 88% of the sialic acid had been removed. Strain B16B6 was resistant to the alternative pathway-mediated bactericidal activity of both absorbed and hypogammaglobulinemic human sera, whereas noncapsular variant 2T4-1 was sensitive to these sera. The addition of purified immune immunoglobulin M (IgM) and IgG significantly increased the alternative pathway-mediated killing of strain B16B6 organisms. IgM mediated increased bactericidal activity without an increase in C3 or factor B deposition. In contrast, the IgG-mediated killing was associated with increased binding of C3 and factor B to the organisms. Absorption studies showed that the IgM bound to the sialic acid capsule, whereas the IgG bound to noncapsular surface antigens. We conclude from these results that the group B meningococcal sialic acid capsule inhibits activation of the alternative pathway in the nonimmune host and that both IgM and IgG, although specific for different surface antigens, are capable of augmenting the alternative pathway-mediated killing of group B meningococci. PMID- 3098683 TI - Chemical characterization of binding properties of opacity-associated protein II from Neisseria gonorrhoeae. AB - Binding of an opacity-associated protein II (PIIop) from Neisseria gonorrhoeae to eucaryotic macromolecules was studied. HeLa cell extracts were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to nitrocellulose, and purified PIIop bound to approximately 50 distinct molecular species. The binding of PIIop to HeLa cell components was stable in high salt and nonionic detergent and was not inhibited by a variety of monosaccharides and polyionic substances. PIIop binding behavior was compared with that of two model carbohydrate-binding proteins, wheat germ agglutinin (WGA) and concanavalin A (ConA). Model glycoproteins (ovomucoid, fetuin, mucin, ovalbumin) inhibited binding by PIIop, WGA, and ConA to various degrees. HeLa cell glycopeptides, generated by pronase digestion of chloroform-methanol-extracted cells, were tested for their ability to inhibit binding by PIIop to Western blots of HeLa cell macromolecules. HeLa cell extracts inhibited PIIop binding before pronase treatment, but inhibitory activity was lost as a result of pronase digestion. Direct binding to defined glycosylated and nonglycosylated proteins revealed that ConA and WGA bound only glycoproteins, whereas PIIop bound to proteins lacking carbohydrate as well. PIIop binding to human and bovine serum albumins was of high affinity and required partial unfolding of albumin; native albumin was not bound by PIIop; however, both the denatured, reduced form of albumin and the compact, nonreduced form of carboxymethylated albumin were bound strongly by PIIop. Albumin-PIIop interaction did not involve covalent bond formation through sulfhydryl groups. The predominant binding interactions of PIIop found in this study were with protein rather than carbohydrate, and the chemical nature of the interactions is more complex than involvement of purely ionic or hydrophobic forces. PMID- 3098685 TI - Isolation of Coccidioides immitis F antigen by immunoaffinity chromatography with monospecific antiserum. AB - Detection of antibody to Coccidioides immitis F antigen is of proved value in the diagnosis of coccidioidomycosis. This antibody is demonstrable by use of an immunodiffusion assay with reference coccidioidin antigen and antiserum to C. immitis. Using a combination of lectin affinity and immunoaffinity chromatography, we isolated the F antigen from coccidioidin and prepared monospecific antibody to the purified antigen. The availability of these reagents will enable the development of a sensitive and specific assay for detecting serologic reactivity to this antigen. PMID- 3098687 TI - Characterization of protein I from serum-sensitive and serum-resistant transformants of Neisseria gonorrhoeae. AB - The protein IAs of serum-sensitive (FA635) and serum-resistant (FA638) transformants of Neisseria gonorrhoeae, which have identical pedigrees, have been shown to be different by the use of a monoclonal antibody and were also shown to be different by proteinase K cleavage and primary structural and surface peptide mapping. The difference in structure is within the surface-exposed region of the molecule. The only other difference observed between the two strains was a very slight difference in lipooligosaccharide silver staining in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These data suggest that protein I alone or in combination with lipooligosaccharide may significantly contribute to serum resistance. PMID- 3098686 TI - Rickettsia prowazekii requires host cell serine and glycine for growth. AB - The growth requirement of Rickettsia prowazekii for the amino acids serine and glycine was assessed in both wild-type cell lines and a mutant cell line. X irradiated L929 cells supported the growth of R. prowazekii when the cells were incubated in Eagle minimal essential medium supplemented with serum. In contrast, in this medium, X-irradiated Vero cells did not support the growth of rickettsiae unless cycloheximide, serine, or glycine was added. Other nonessential amino acids, additional glucose, and potential products of host cell metabolism of serine and glycine were nonstimulatory. The concentration of serine or glycine required to support rickettsial growth had no effect on the doubling time of uninfected, unirradiated Vero cells. A comparison of intracellular amino acid pools indicated that the serine and glycine concentrations in mock-infected Vero cells were approximately 31 and 14% of the respective concentrations in mock infected L929 cells. The pools of both amino acids in Vero cells increased markedly upon treatment of the cells with cycloheximide. Interconversion of serine and glycine catalyzed by serine hydroxymethyltransferase was detected in cell-free extracts of purified rickettsiae. However, this enzymatic activity did not permit rickettsial growth in a glycine-requiring clone (772-56d) of the Chinese hamster ovary cell CHO-K1 in the absence of glycine supplementation. These data indicate that R. prowazekii depends on the host cell for serine or glycine. PMID- 3098688 TI - Differential growth characteristics and immunogenicity of tight and coasting temperature-sensitive mutants of Pseudomonas aeruginosa. AB - Genetically attenuated vaccines capable of limited replication in the vaccinate may elicit stronger, longer-lasting immunity than that induced by component, killed whole-cell, or nonreplicating live vaccines. We have isolated and partially characterized temperature-sensitive Pseudomonas aeruginosa mutants of two different phenotypes: a tight mutant, which ceases all growth immediately after its transfer to 36 degrees C, and a coaster, which continues to replicate for five generations at 36 degrees C. The growth profiles of the two temperature sensitive phenotypes were compared both in vitro and in vivo; maintenance of the coasting phenotype in vivo was confirmed. The immunogenicity of the two phenotypes was compared in two models. In model 1, ICR mice were immunized intraperitoneally (i.p.) with graded doses of either mutant and challenged 3 weeks later i.p. with lethal doses of the wild-type strain. In model 2, DBA/2J mice were immunized intranasally with either mutant and subsequently challenged with an aerosolized inoculum of the wild-type strain, and lung clearance was measured over 4 h. In both models, the coaster demonstrated slightly higher immunogenic potential and, in addition, induced significantly higher levels of immunotype-specific serum immunoglobulin G after i.p. immunization. PMID- 3098689 TI - Surface markers of human lymphokine-activated killer cells and their precursors. Analysis at the population and clonal level. AB - Lymphokine-activated killer (LAK) activity was first analyzed on PBL populations fractionated on the basis of the expression of T11 or T3 antigen. LAK cell precursors were found to be present in both T11+ and T11- populations, but only in the T3- cell fraction. The generation of LAK activity in highly purified T3- populations of PBL was not accompanied by expression of T3 antigen during a 5-day culture period. LAK activity was next analyzed at the level of limiting dilution clonal microcultures. T11+T3- and T11+T3+ cells, cloned under optimal culture conditions, gave a frequency of proliferating cells of approximately 1 cell in 1.25 for T11+T3+ and 1 cell in 10 for T11+T3- cells. Clones were screened for their ability to lyse fresh ovarian carcinoma cells and K562 target cells. The majority of LAK clones were derived from the T11+T3- cells; moreover, most of the clones derived from these cells displayed LAK activity. Clones displaying LAK activity lysed a panel of fresh or cultured tumor target cells, but failed to lyse PHA-activated lymphoblasts. Surface marker analysis indicated that all the clones had maintained the original T11/T3 phenotype. Whereas 2 T3+ selected LAK clones expressed the T8+T4- phenotype, only 1 out of 9 T3- clones was T8+T4-, all the others lacking both T4 and T8 antigens. PMID- 3098690 TI - Establishment and characterization of three new malignant lymphoid cell lines. AB - We have established 3 new EBV-negative cell lines, designated Sc-1, Ri-1 and Ci 1, from patients with B-cell lymphoma/leukemia. We characterized them by cytogenetics and by study of surface membrane antigens with a panel of monoclonal antibodies (MAbs), surface and cytoplasmic immunoglobulin (Ig) expression and Ig heavy- and light-chain genes. All 3 lines had a 14q+ abnormality. Ri-1 also had translocations involving chromosomes 2, 8 and 18. Ci-1 also had abnormalities involving chromosomes 2, 8 and 22 and its karyotype was 46, XX, t(2;8), t(14;22). The t(2;8) had the same breakpoints as those reported in some cases of Burkitt's lymphoma. We also studied a classical Ph1-positive cell line previously established by Pegoraro et al. (1983) and designated BV173. The phenotypes of these 4 lines based on Ig expression and marker studies correlated well with their respective genotypes. Our results are in keeping with the notion that leukaemic cell populations are clonal expansions of cells "frozen" at a particular stage in their differentiation. Specifically, BV173 cells are at an early stage of B-cell differentiation, Ri-1 and Ci-1 cells are at intermediate stages and Sc-1 cells are at a relatively late stage in the B-cell lineage. PMID- 3098692 TI - Thymosin fraction 5: effects on T cell functions in mice immunosuppressed by severe dietary protein deficiency. AB - The present studies were performed to determine the effects of severe protein deficiency and subsequent injection of thymosin fraction 5 (TF5) on T and B cell functions. BALB/c mice, 4 weeks old, were fed a normal protein (21%), a low protein (4%) or a protein free (0%) diet and then injected with TF5 or buffer (PBS). A significant increase was observed in the PHA (phytohemagglutinin) and LPS (lipopolysaccharide) induced mitogenesis with increasing age of the well nourished, PBS injected animals. The severely protein malnourished mice, PBS injected and the well nourished mice, injected with TF5 had smaller increases in both B and T cell mitogenesis with increasing age. TF5 injection of the malnourished mice increased PHA and LPS mitogenesis nearly to the levels of the well-nourished mice. The protein malnourished mice consistently had higher serum corticosteroid levels than controls. No changes in serum corticosteroids were observed with TF5 injection of controls, but there was a significant decrease in the corticosteroid levels of the severely malnourished with TF5 injection. Cytoxicity assays of T cell function, antibody dependent cellular cytoxicity and cytoxicity to mouse thymona tumor cells, in mice fed moderately protein deficient diets showed suppression compared to controls fed 20% protein. TF5 injection partially and temporarily increased these functions in the malnourished mice. PMID- 3098691 TI - Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children. AB - Following a brief outline of current knowledge concerning atherosclerosis and its treatment, the authors describe the results obtained by treating with pantethine (900-1200 mg daily for 3 to 6 months) a series of 7 children and 65 adults suffering from hypercholesterolemia alone or associated with hypertriglyceridemia (types IIa and IIb of Fredrickson's classification). Pantethine treatment produced significant reduction of the better known risk factors (total cholesterol, LDL-cholesterol, triglycerides, and apo-B) and a significant increase of HDL-cholesterol (signally HDL2) and apolipoprotein A-I. The authors conclude with a discussion of these results and of the possible role of pantethine in the treatment of hyperlipoproteinemia, in view of its perfect tolerability and demonstrated therapeutic effectiveness. PMID- 3098693 TI - Modification of the contractile activity of isolated atria by T4 lymphocytes from patients with Chagas' disease: effect of soluble factors. AB - The results of this study show that peripheral blood mononuclear leukocytes of patients with Chagas' disease (Ch-PBMC) respond to challenge with homologous as well as with heterologous heart antigens releasing active soluble factors capable of increasing the contractile tension and frequency of beating rat atria. The reaction was related to T. cruzi infection rather than to the presence of cardiomyopathy. Indirect evidence suggests that supernatants of Ch-PBMC activated with heart tissue homogenates involved the generation of arachidonic acid metabolites by the lipoxygenase system of rat atria. Active effector cells were present in Ch-PBMC that had been depleted of T8-lymphocytes by lysis with OKT8 and rabbit complement (C) and not in those depleted of T4-lymphocytes with OKT4 and C. Therefore, the positive inotropic and chronotropic effects of Ch-PBMC were due to the action of cells from the T4 subset. PMID- 3098694 TI - Plasma lipoprotein profile in relation to sex hormones in premenarcheal athletes. AB - Physical activity of an endurance nature is supposed to affect the lipoprotein profile in adults as well as in children. When examining this profile in premenarcheal athletes, regard has to be paid to an interfering effect of the rising sex hormone levels due to puberty. Therefore, the purpose of this study was to investigate the plasma lipoprotein levels of premenarcheal athletes in relation to their sex hormone profile. Thirty-six elite gymnasts, 21 recreational gymnasts, 27 girl swimmers, and 25 very little active control girls participated. Their age was about 12 years. The sex hormone profiles of all groups were similar. The swimmers had the lowest level of TC, LDL-C, and TG (P less than or equal to 0.05), and apo A-I was elevated in this group as compared with the others (P less than or equal to 0.05). HDL-C was highest in the recreational gymnasts (P less than or equal to 0.05). The elite group and the control group had similar lipoprotein profiles. After adjustment for T and E-2, no change in variance of the lipoproteins was found. A low correlation existed between apo A I, E-2, and T (P less than or equal to 0.05). Thus, in this pediatric population, the sex hormones did not play a significant role relative to the levels of plasma lipids or apo A-I. As the body composition correlated very weakly with TG, it is tentative to conclude that the variance found in the lipoprotein profile might be due to differences in physical activity. Moreover, genetic factors may have contributed to the variance. PMID- 3098695 TI - Differential radiosensitization of human tumour cells by 3-aminobenzamide and benzamide: inhibitors of poly(ADP-ribosylation). AB - The effect of 3-aminobenzamide (3AB) and benzamide (BZ) (inhibitors of poly(ADP ribose) synthetase) on radiosensitivity was investigated in normal human fibroblasts and three human cell lines established from tumours with varying degrees of clinical radiocurability. The human tumour cell lines selected were: Ewing's sarcoma, a bone tumour usually considered radiocurable with moderate radiation doses; lung adenocarcinoma, a tumour considered radiocurable with high doses of radiotherapy; and osteosarcoma, a very resistant tumour which is rarely controlled by standard doses of radiotherapy. Poly(ADP-ribose) synthetase inhibitors were added to cultures 2 h prior to irradiation and removed 24 h after. Inhibitors were used at doses producing little or no toxicity in cells. In the presence of these inhibitors, a differential radiosensitization was observed. Ewing's sarcoma cells and normal human fibroblasts were sensitized to an equal extent by either 8 mM 3AB or 4 mM BZ. However, no sensitization was observed at these concentrations in the lung adenocarcinoma cells or osteosarcoma cells. The degree of radiosensitization in vitro by 3AB and BZ correlates well with the clinical radiocurability of these tumours in vivo. PMID- 3098696 TI - Suppurative thrombophlebitis: correlation between pathogen and underlying disease. AB - We identified 29 episodes of suppurative thrombophlebitis in 27 patients admitted to a large general hospital between May 1980 and May 1984. In 25 patients, the intravenous cannulae had been in place for more than 3 days. Streptococcus faecalis, Pseudomonas aeruginosa or one of the Enterobacteriaceae were implicated in 14 patients. All these patients had recently undergone abdominal surgery or had a major intra-abdominal inflammatory process at the time they developed thrombophlebitis. The remaining 13 patients were infected with Staphylococcus aureus, other gram-positive cocci or Candida species. Only two of these had an active abdominal process at the time of their infection (chi 2 = 16.08, P less than 0.001). There is an apparent association between phlebitis caused by enteric organisms and active intra-abdominal pathology. There were two deaths related to delayed or deferred surgery. Suppurative thrombophlebitis is a lethal, preventable nosocomial infection that requires urgent surgical intervention. PMID- 3098697 TI - The enterococcus. PMID- 3098698 TI - [Hereditary coproporphyria with grand mal epilepsy, glucose-6-phosphate dehydrogenase deficiency and phenobarbital tolerance]. PMID- 3098699 TI - Serological cross-reactions between Rickettsia typhi, Proteus vulgaris OX19, and Legionella bozemanii in a series of febrile patients. AB - The sera of 19 patients with a febrile disease of undetermined etiology were positive in the indirect immunofluorescence assay (IFA) to Legionella bozemanii serogroup 1 (Lb) and Rickettsia typhi (Rt). To both antigens, high titers of IgG class and IgM-class antibodies were demonstrated. Several of the patients also had positive IFA and Weil-Felix reactions to Proteus vulgaris OX19 (PX 19). A sharp reduction of the serotiters to all three antigens was achieved by absorption of the sera with any one of the organisms. We demonstrated, by crossed immunoelectrophoresis with an Lb extract and a rabbit reference anti-Lb serum, that a heat-stable and trypsin-resistant antigen (antigen no. 1) reacted consistently with patients' sera that had been incorporated into an intermediate gel. Sera from five patients with high-titer IFA reactions to Rt, but no reaction to Lb, showed no interaction with antigen no. 1. PMID- 3098700 TI - Sucralfate protection against gastrointestinal damage: possible role of prostanoids. AB - The protective effect of sucralfate against gastric and intestinal mucosal damage was studied in rats. Sucralfate (125 mg) significantly reduced gastric mucosal lesion formation induced by s.c. administration of indomethacin (30 mg/kg) or intragastric administration of aspirin (100 mg/kg), HCl (0.6 N), NaOH (0.2 N) or sodium taurocholate (30 mM). Furthermore, when given in three doses of 125 mg each, sucralfate significantly decreased the development of small intestinal lesions induced by indomethacin in the re-fed rat. Gastric mucosal cyclooxygenase activity in sucralfate-treated rats expressed as prostaglandin E2 formation--388 +/- 140 (ng/g wet weight; mean +/- SE)--was significantly higher (P less than 0.01) than its activity in the control--264 +/- 62 (ng/g wet weight). Sucralfate also slightly, but significantly, decreased indomethacin-induced gastric mucosal cyclooxygenase inhibition. Intestinal mucosal cyclooxygenase activity was not affected by sucralfate. The results suggest that gastric and intestinal mucosal damage induced by various ulcerogens is significantly reduced by sucralfate. Sucralfate-induced stimulation of endogenous gastric mucosal prostanoid formation may in part explain its effective protective properties. PMID- 3098701 TI - Protection by mild irritants against indomethacin-induced gastric mucosal damage in the rat: role of prostaglandin synthesis. AB - "Mild irritants" have been shown to protect rat gastric mucosa from damage induced by noxious topical agents, supposedly by induction of mucosal prostaglandin (PG) biosynthesis. The protective effect of NaCl 5%, ethanol 20%, NaOH 0.075 N, HCl 0.35 N, salicylic acid 100 mg/kg and paracetamol 200 mg/kg was investigated in rats treated with an ulcerogenic dose (25 mg/kg) of indomethacin; mucosal PG synthesis was simultaneously determined. Significant protection was achieved only with NaCl 5%, salicylic acid and paracetamol. Salicylic acid and paracetamol significantly decreased acid secretion and enhanced PGE2 or 6-keto PGF1 alpha generation in control rats, while a small but significant change in the indomethacin-inhibited PG synthesis was observed after treatment with NaCl 5% or salicylic acid. We conclude that protection by "mild irritants" against indomethacin-induced mucosal damage may involve increased cytoprotective PG generation, as shown for paracetamol and salicylic acid, or partial blocking of indomethacin binding at the cyclooxygenase receptor site, as shown for NaCl 5% and salicylic acid. PMID- 3098702 TI - Prospective payment systems: steps to enhance quality, efficiency, and regionalization. AB - The prospective payment system has many benefits and risks for the hospital industry. A quality-enhancing bidding process can be used to redistribute any unfair windfall profits, and foster quality care, effectiveness, efficiency, and productivity. PMID- 3098703 TI - Tissue-type plasminogen activator: a new fibrinolytic agent. PMID- 3098704 TI - Chelating agents for the binding of metal ions to antibodies. AB - The development and applications of bifunctional chelating agents are reviewed, with emphasis on the preparation of radiolabeled monoclonal antibodies suitable for use in vivo. Major principles and practical aspects of the chemical procedures are outlined, and new results of interest for future work are described. PMID- 3098705 TI - A bifunctional ligand for Pd(II). AB - A bifunctional ligand, 6-(5-carboxyl pentyl)-5,7 dioxo-1,4,8, 11 tetraazaundecane, has been shown to produce a neutral, inert complex with Pd(II). The complex is formed in high yield and is stable over a wide pH range. It can be conjugated to proteins through the carboxylic acid side arm using a carbodiimide coupling reagent and may be useful for labeling antibodies or other large molecules. PMID- 3098706 TI - Monoclonal antibodies as reversible equilibrium carriers of radiopharmaceuticals. AB - We have prepared monoclonal antibodies (MoAbs) with the specific ability to bind metal chelates such as 111In benzyl EDTA. One, 10, 50 and 100 micrograms MoAb CHA255 Kb = 4 X 10E9 was complexed with 111In BLEDTA II, BLEDTA IV, and benzyl EDTA and injected i.v. in Balb/c mice with KHJJ tumor. The biological half-life by whole body counting was profoundly altered for all three compounds; from minutes to hours with 10 micrograms; to days with 100 micrograms. Tumor uptake increased 50 fold at 24 h with increasing MoAb but satisfactory tumor concentrations (3% per g) and tumor/blood ratios (1.8:1) were obtained with an amount equivalent to 7 mg for a human. Blood level and whole body activity were decreased 30-50% within 3 h or i.v. injection of a "flushing" dose of unlabeled indium benzyl EDTA, increasing tumor/blood ratios to 50:1. PMID- 3098707 TI - Congenital anterior urethral diverticulum associated with bilateral urinomas and dysplastic kidneys. AB - Congenital anterior urethral diverticulum (AUD) is a rare condition. We report a case of AUD associated with urinary ascites, bilateral urinomas and dysplastic kidneys. The diagnosis of urethral obstruction was established in utero by means of ultrasound. The right perirenal urinoma appeared "septated", and we believe that this is related to its hemorrhagic content. Improvement of the clinical condition and renal function was noted after decompression by bilateral cutaneous loop ureterostomy. PMID- 3098708 TI - [Cerebro-oculo-muscular syndrome]. AB - The case of a newborn with COMS is reported. The patient presented hydrocephalus, malformations of the eye and congenital myopathy. Typical pathological changes are interpreted as belonging to type II lissencephaly. Relationships to other similar but not identical syndromes are discussed. PMID- 3098710 TI - Comments on justifying the cost of treatment. PMID- 3098709 TI - Expression of differentiation antigens by hybrids of human lymphoblastoid cells. AB - In previous communications, we have described the expression of class I and class II histocompatibility antigens by hybrids of human B and T lymphoblastoid cell lines (B- and T-LCL). In all cases, such hybrids were found to resemble their B LCL parents, expressing high levels of class I and class II antigens encoded by both parent cell lines. In the current study, we have conducted a more extensive analysis of B-LCLxT-LCL hybrids with a panel of monoclonal antibodies recognizing a variety of B and T lymphocyte differentiation markers. Rather than exhibiting a B-LCL-dominant phenotype, most hybrids were found to express a majority of both T and B lymphocyte antigens expressed by their parent cell lines. Several hybrids of pairs of dissimilar T-LCL were also produced and analyzed. Again, a majority of parental antigens was expressed on the hybrids. However, eight of eight hybrids of the T-LCL CEM and HSB failed to express HNK-1, an antigen strongly expressed by HSB; and two hybrids of the T-LCL CEM and SKW3 expressed CD3, an antigen expressed by neither parent cell line. PMID- 3098711 TI - Trypanosoma cruzi infection in a dog from Oklahoma. AB - A dog with signs of weakness, labored breathing, and generalized edema was examined. It was heavily infested with fleas and had wounds resulting from a recent fight. Hematologic findings were not remarkable, except for parasites in the blood. The dog was treated for fleas and given antibiotics, but was euthanatized when it failed to respond. Blood and tissue specimens were found to contain Trypanosoma cruzi, and the serum contained antibodies to the organism. We believe this is the first confirmed case of T cruzi infection in dogs from Oklahoma. The public health implications of this finding are underscored by a report on the detection of T cruzi in raccoons in the same season and geographic area. PMID- 3098712 TI - Localization of the gene for glutathione S-transferase P on rat chromosome 1 at band q43. AB - An intron fragment of a rat glutathione S-transferase P (GST-P) genomic clone was used to assign the chromosomal localization of the GST-P gene. In situ hybridization analysis with the genomic DNA indicated that the GST-P gene was localized on band q43 of rat chromosome 1. PMID- 3098713 TI - Regional location of a novel yes-related proto-oncogene, syn, on human chromosome 6 at band q21. AB - A novel v-yes-related proto-oncogene, syn, was assigned to region q21 of human chromosome 6 by in situ molecular hybridization. The present regional mapping substantiated the previous assignment that was performed by analyses of human mouse somatic cell hybrids and filter blot hybridization. PMID- 3098714 TI - A single dominant susceptible gene determines spontaneous development of thymoma in BUF/Mna rat. AB - Rats of the BUF/Mna strain developed spontaneous epithelial thymomas morphologically indistinguishable from human homologues at virtually 100% incidence. Segregation of thymoma development among crosses between BUF/Mna and ACI/NMs, which has 0% thymoma incidence, indicated that thymoma susceptibility was determined principally by a single autosomal dominant gene Tbm-1 (thymoma in BUF/Mna rats). In these crosses, another autosomal dominant or semidominant gene(s) contributed by ACI/NMs parents moderately reduced the thymoma incidence. PMID- 3098715 TI - T cell receptor beta chain gene rearrangements in leukemias with immature T cell phenotype. AB - The arrangements of the T cell receptor (TCR) beta genes were studied in leukemias with immature T cell phenotype. Three cases of acute lymphocytic leukemia (ALL) and one case of chronic myelocytic leukemia in blastic crisis (CML BC), which expressed only Tp40 antigen of cluster of differentiation (CD) 7 without erythrocyte rosette receptor (E), did not show rearrangements of TCR beta chain genes. Two of 5 ALL cases which expressed an additional T cell antigen, T1 of CD5, showed rearrangements of TCR beta genes. Two cases of CML-BC expressing T1 and Tp40, however, had unrearranged TCR beta genes. The results altogether showed that a part of E- T1+ Tp40+ ALL cases is of T cell origin. PMID- 3098716 TI - Changes in the urine and scanning electron microscopically observed appearance of the rat bladder following treatment with tumor promoters. AB - Urine of rats treated with promoters of urinary bladder carcinogenesis was analyzed during weeks 8 to 24 of administration. The sodium salts of several chemicals, including ascorbic acid, erythorbic acid, acid saccharin and o phenylphenol increased the urinary pH and sodium ion concentration of the urine. In contrast, treatment with sodium hippurate did not cause elevation of urinary pH although it increased the sodium ion concentration in the urine. Butylated hydroxyanisole, butylated hydroxytoluene (BHT), and ethoxyquin did not affect the urinary pH or any electrolytes except for an increase of phosphorus in the urine of rats given BHT or ethoxyquin. Scanning electron microscopic examination showed that epithelial cells of the urinary bladder of rats given promoters of urinary bladder carcinogenesis had pleomorphic microvilli, short, uniform microvilli, and ropy or leafy microridges on their surfaces. Thus, for the class of promoters including the sodium salts of weak to moderate acids, the elevation of urinary pH and the increase of sodium ion concentration accompany the promoting activity, whereas these changes do not occur following administration of the antioxidant class of bladder tumor promoters. PMID- 3098717 TI - Sequential changes of the forestomach of F344 rats, Syrian golden hamsters, and B6C3F1 mice treated with butylated hydroxyanisole. AB - Butylated hydroxyanisole (BHA) was given to F344 rats, Syrian golden hamsters and B6C3F1 mice at 2 doses for up to 104 weeks. The two doses were 2.0% and 1.0% for rats and hamsters, and 1.0% and 0.5% for mice. Animals were sacrificed sequentially at 8-week intervals from week 8 to week 104, and the carcinogenic effects of BHA on the forestomach were examined histopathologically. Papillomas and carcinomas were found in rats, hamsters and mice. In rats, papillomas first appeared in week 8 in the group given the higher level of BHA and in week 56 in that given the lower level. The first carcinoma was observed in week 48 in rats given the high level, while no carcinoma was observed in rats given the lower level. In hamsters, papillomas appeared in week 8 in both BHA-treated groups, and in both groups, the incidence of papillomas was much higher than in BHA-treated rats. Squamous cell carcinomas were observed in 4 hamsters (10.0%) among those that survived more than 64 weeks on treatment with the higher level of BHA and in 4 (7.3%) among those treated with the lower level. In mice, papillomas were induced by BHA in both BHA-treated groups after more than 88 weeks. Although the incidence was not statistically significant, carcinoma was also seen in mice, suggesting that BHA may also be carcinogenic to mouse forestomach. PMID- 3098718 TI - Inhibitory effect of dibutyltin dichloride on pancreatic adenocarcinoma development by N-nitrosobis(2-oxopropyl)amine in the Syrian hamster. AB - The effects of a single intragastric application of dibutyltin dichloride (DT), at a dose of 30 mg/kg body weight, on N-nitrosobis(2-oxopropyl)amine (BOP) induced pancreatic carcinogenesis were studied in female Syrian golden hamsters. DT, which has been shown to selectively induce bile duct injury, was administered either 1 week before or after BOP initiation. BOP was injected subcutaneously once a week for 5 weeks at a dose of 10 mg/kg body weight. Controls were injected with BOP alone or given DT without carcinogen. Animals sacrificed at the end of the 25-week experimental period showed a significant inhibitory effect of DT on pancreatic carcinoma induction when DT was given before BOP treatment, although no such influence was evident with DT treatment following BOP exposure. These results indicate that the bile duct and more especially common bile-duct injury induced by DT may be relevant to the inhibition of the initiation stage of BOP induced pancreatic carcinoma development in Syrian hamsters. PMID- 3098719 TI - Histopathological changes in transplanted mouse mammary carcinoma following hyperthermia with or without radiation. AB - The histopathological effects of hyperthermia with or without radiation were investigated in a transplanted mouse mammary carcinoma. Since the histopathological changes following hyperthermia differed greatly between the center and periphery of a tumor, we analyzed the changes in each area separately according to a semi-quantitative method developed by us. Three days after hyperthermia at 44 degrees for 45 min, undamaged tumor cells were found mostly in the tumor periphery adjacent to normal tissues. This phenomenon was observed when the entire tumor could be heated almost homogeneously. When a tumor was treated by heat alone, the thermal damage disappeared 7 days after treatment. On the other hand, treatment with hyperthermia plus radiation caused pronounced damage in the tumor center and tumor periphery 7 and 14 days after treatment. These combination effects depended on the radiation dose. The present findings demonstrate that combination of high doses of irradiation and hyperthermia is very effective for potentiating the thermal damage in the tumor periphery. PMID- 3098720 TI - Effects of step-up and step-down heating on a transplantable murine tumor. AB - The effects of step-up (42----44 degrees sequence) and step-down (44----42 degrees sequence) heating were studied on a transplantable mammary adenocarcinoma of C3H/He mouse. Tumor-bearing legs were immersed in a water bath and the response to hyperthermia was evaluated in terms of the delay in tumor growth. Tumor growth was delayed greatly with increase in the duration of treatment with 44 degrees hyperthermia, whereas with 42 degrees hyperthermia of up to 180 min, tumor growth was delayed only slightly. The effects of step-up heating were similar to those of 44 degrees hyperthermia alone and the response was enhanced by a factor of 0.9-1.1 with the 60-min treatment at 42 degrees followed by treatment at 44 degrees. Thermal resistance developed when the preheating time at 42 degrees was longer than 30 min. On the other hand, the tumor response was markedly enhanced by step-down heating by a factor of 1.8-2.4 with the treatment at 44 degrees followed by 60-min treatment at 42 degrees. Since the enhancement factor for skin damage found previously was similar to that for the tumor, therapeutic gain cannot be expected by the use of these combined heat treatments. PMID- 3098721 TI - Radioimmunoscintigraphy of human gastric carcinoma xenografts with 125I-labeled monoclonal antibody. AB - A monoclonal antibody (GC 302) established in our laboratory, which was reactive with gastric carcinoma and other epithelial carcinoma but not with normal gastric mucosa or other malignant tumors of mesenchymal origin, was used to investigate the radioimmunolocalization of tumors. Various kinds of target cells (5 X 10(5)) were incubated with 125I-labeled GC 302, and radioactivity was determined with a gamma counter. It was shown that there was a 500- to 1,000-fold increase in counts for gastric carcinoma (NUGC-2, NUGC-4, MKN-28 and MKN-45) as compared to those of normal lymphocytes and about 100-fold increase as compared to melanoma or leukemia. These findings were consistent with those obtained from the study of immunohistochemistry using GC 302. An in vitro assay was also carried out using nude mice bearing gastric cancer and inoculated with 125I-labeled GC 302. There was a 2- to 3-fold increase in radioactivity in the tumor and a 4- to 5-fold increase as compared with the visceral organs. Although the tumor:blood ratio was relatively low, radioimmunoscintigraphy could be done successfully with the aid of computed radiography. We thus conclude that further testing of GC 302 is worthwhile to establish whether or not it is useful for radioimmunoscintigraphy of metastatic lesions of gastric cancer for possible clinical application. PMID- 3098722 TI - Human monoclonal antibody reactive to stomach cancer produced by mouse-human hybridoma technique. AB - Production of human monoclonal antibodies reactive to stomach cancer was attempted by the hybridoma technique using splenic lymphocytes from stomach cancer patients. The parental cells used were NS-1 mouse myeloma line and three human lines including RPMI-1788 6TGR, which was established in our laboratories. Ten mouse-human and two human-human (from the fusion with RPMI-1788 6TGR) hybridomas have been producing IgM antibody for over 18 months, and all the heterohybridomas yielded ascites when transplanted into nude mice. Four antibodies produced by the heterohybridomas were selected and analyzed. These 4 antibodies, 3F6, 4A10, 3H5 and 1F9, reacted predominantly to cytoplasmic antigens of stomach and other epithelial cancer lines. The reactivity against human tumors transplantable in nude mice showed that all antibodies but 3F6 were reactive with stomach and lung cancers. Smears prepared from normal and cancer tissues were also tested, and these 4 antibodies showed positive reactions not only to stomach cancer, but also to normal stomach and colon. The reactivity against fetal tissues demonstrated that 3H5 antibody was reactive with epithelium of the stomach, and 1F9 antibody was positive with epithelium of the respiratory tract and bile duct, but the other two were negative. Thus, the serological analysis showed that the antigens detected are not tumor-specific, but are differentiation antigens. Chromosome analysis of these 4 mouse-human hybridomas and another one, which seems to produce an antibody against keratin, showed that three retained human chromosome 14 on which immunoglobulin heavy chain (Ig H) gene is located, but two did not. Southern blot analysis, however, revealed that all 5 hybridomas had a human Ig H gene. PMID- 3098723 TI - Expression of H-2 antigens and inducibility of antitumor immune responses in various tumor cell clones established from methylcholanthrene-induced fibrosarcomas. AB - A large number of fibrosarcoma cell lines was established in vitro from a tumor mass induced freshly by inoculating 3-methylcholanthrene (MCA) subcutaneously (sc) into C3H/HeN mice, and more than five clones were isolated from each cell line by the limiting dilution technique. The present study investigated a) qualitative and quantitative comparison of the immunogenicity [tumor-associated transplantation antigen (TATA) activity] of different tumor clones and b) the relationship between such immunogenicity and the expression of H-2 class I antigens. When TATA were compared between different clones from the same tumor, these TATA were revealed to be cross-reactive to each other. On the other hand, the comparison of TATA between clones from different tumors demonstrated the existence of individually unique TATA in these clones. In addition to qualitative heterogeneity of TATA from different tumors, the magnitude of immunogenicity was also heterogeneous in the individual clones established. Whether or not such quantitative heterogeneity of immunogenic strength was related to the expression of H-2 (class I) antigens was examined by flow microfluorometry studies using anti-H-2k antibodies. The results demonstrated that there was no correlation between TATA activity capable of inducing in vivo tumor resistance and the expression of H-2 antigens. This contrasted with parallelism between the expression of H-2 antigens and inducibility of cytotoxic T lymphocytes (CTL) or lysability of tumor cell clones by CTL. These results are discussed in the context of the cellular mechanism of tumor cell eradication in vivo and the regulation of cell surface H-2 expression in vitro and in vivo. PMID- 3098725 TI - Influence of fetal calf serum on growth-inhibitory activity of human recombinant gamma-interferon (GI-3) in vitro. AB - The growth-inhibitory activity of human recombinant gamma-interferon (rIFN-gamma: GI-3) against 30 human cultured cell lines derived from leukemias and lymphoma (9 T-cell, 13 B-cell, 2 nonTnonB and 6 myeloid cell lines) was measured quantitatively by in vitro regrowth assay. Only three myelomonocytoid cell lines (HL-60, U937 and THP-1-0) were found to be sensitive, and HL-60 was the most sensitive. However, the sensitivity of HL-60 was found to be much influenced by both the batch and the concentration of fetal calf serum (FCS) used in the experiment. In the experiments using a certain FCS, GI-3 had a high antiproliferative activity against HL-60 at the optimal concentration (10(4) 10(5) U/ml), when assayed in medium containing 10% FCS. Both lower and higher concentrations of the interferon than 10(4)-10(5) U/ml resulted in decreased antiproliferative activity. When a high concentration (30%) of the FCS was employed in the assay, the antiproliferative activity of GI-3 was also much reduced. In the experiments using the other FCS, no antiproliferative activity of GI-3 against HL-60 was observed on assay in the medium containing 10% FCS, but significant antiproliferative activity was observed in the medium containing 30% FCS from the same source. Experiments using serum-free culture medium revealed that GI-3 itself had both a slight growth-inhibitory action at the optimal concentrations (at about 10(4) U/ml) and growth-enhancing activity at high (10(6) U/ml) concentration. The antiviral titer of GI-3 was stable during 72 hr of incubation in growth medium with or without cells. These findings suggest that there are cofactors in the serum which positively or negatively influence the growth-regulatory activity of GI-3 against HL-60 cells. PMID- 3098724 TI - Requirements of adherent cells for activating Lyt-1+2- T cells as well as for functioning as antitumor effectors activated by factor(s) from Lyt-1+2- T cells. AB - The mechanism by which tumor-specific Lyt-1+2- T cells exhibit their antitumor effect in collaboration with an adherent cell population was investigated with the use of a double diffusion chamber. The double diffusion chamber was prepared by separating the two chambers from each other by a Millipore membrane and implanted in the peritoneal cavity of C3H/He mice. When one chamber contained normal C3H/He spleen cells plus syngeneic viable MH134 hepatoma cells and the other contained normal C3H/He spleen cells plus syngeneic viable X5563 plasmacytoma cells, tumor cells in both chambers continued to proliferate. In contrast, the injection of spleen cells immunized to the MH134 tumor into one (the first) chamber containing MH134 tumor cells not only resulted in the growth inhibition of MH134 tumor cells, but also exhibited an appreciable inhibitory effect on the growth of X5563 tumor cells admixed with normal spleen cells in the other (second) chamber. The growth inhibition of X5563 tumor cells in the second chamber was mediated by Lyt-1+2- T cells specific for MH134 tumor cells admixed in the first chamber. Such tumor-specific Lyt-1+2- T cell function was dependent on the existence of adherent cells in the first chamber, and adherent cells in the second chamber were also required for the X5563 growth inhibition. In addition, when the second chamber containing adherent cells, instead of the connection to the first chamber, was provided with macrophage-activating factor (MAF), X5563 growth inhibition was also observed. These results indicate that adherent cells are required for activating tumor-specific Lyt-1+2- T cells and for functioning as nonspecific antitumor effector cells activated by factor(s) such as MAF from Lyt-1+2- T cells. PMID- 3098726 TI - Stimulation of pig growth performance by porcine growth hormone and growth hormone-releasing factor. AB - The current study was undertaken to determine the effects of human growth hormone releasing factor [hpGRF-(1-44)-NH2] on growth performance in pigs and whether this response was comparable to exogenous porcine growth hormone (pGH) treatment. Preliminary studies were conducted to determine if GRF increased plasma GH concentration after iv and im injection and the nature of the dose response. Growth hormone-releasing factor stimulated the release of pGH in a dose-dependent fashion, although the individual responses varied widely among pigs. The results from the im study were used to determine the dose of GRF to use for a 30-d growth trial. Thirty-six Yorkshire-Duroc barrows (initial wt 50 kg) were randomly allotted to one of three experimental groups (C = control, GRF and pGH). Pigs were treated daily with 30 micrograms of GRF/kg body weight by im injection in the neck. Pigs treated with pGH were also given 30 micrograms/kg body weight by im injection. Growth rate was increased 10% by pGH vs C pigs (P less than .05). Growth rate was not affected by GRF; however, hot and chilled carcass weights were increased 5% vs C pigs (P less than .05). On an absolute basis, adipose tissue mass was unaffected by pGH or GRF. Carcass lipid (percent of soft-tissue mass) was decreased 13% by GRF (P less than .05) and 18% by pGH (P less than .05). Muscle mass was significantly increased by pGH but not by GRF. There was a trend for feed efficiency to be improved by GRF; however, this was not different from control pigs. In contrast, pGH increased feed efficiency 19% vs control pigs (P less than .05). Chronic administration of GRF increased anterior pituitary weight but did not affect pituitary GH content or concentration. When blood was taken 3 h post-injection, both GRF- and pGH-treated pigs had lower blood-urea nitrogen concentrations. Serum glucose was significantly elevated by both GRF and pGH treatment. This was associated with an elevation in serum insulin. These results indicate that increasing the GH concentration in blood by either exogenous GH or GRF enhances growth performance. The effects of pGH were more marked than for GRF. Further studies are needed to determine the optimal dose of GRF to administer in growth trials and the appropriate pattern of GRF administration in order to determine whether GRF will enhance pig growth performance to the extent that exogenous pGH does. PMID- 3098727 TI - The role of ciliate protozoa in nutrition of the ruminant. AB - The effects of ciliate protozoa on the ruminal ecosystem, digestion in different parts of the gut, the nature of nutrients available for absorption and their effects upon the nutrition and productivity of their host are reviewed. Compared with fauna-free ruminants, the presence of ciliate protozoa results in a more stable ruminal fermentation, higher levels of ammonia, reduced numbers of bacteria, as well as changes in dry matter (%), liquid volume and turnover rate of ruminal contents. Associated with these differences in the rumen are higher ruminal and total tract digestion of organic matter and fiber in faunated animals. A reduction in net microbial synthesis and an increase in dietary protein degradation in the rumen results in the flow of protein to the small intestine being lower in faunated ruminants. The major nutritional effect of the ciliate protozoa is to change the ratio of protein to energy in the nutrients absorbed, with faunated animals having lower protein and higher energy availabilities compared with ciliate-free ruminants. Of the nutrients available for absorption, the ciliates have no consistent effect on the proportions of volatile fatty acids or amino acids. However, there is evidence that hydrogenation of lipids is increased, as is the supply of choline, and that the bioavailability of copper is reduced by the presence of ciliates. Defaunation of young growing ruminants that are fed high energy diets, containing low levels of ruminal nondegradable protein, results in increased growth rate and feed efficiency. It is unlikely, with the possible exception of wool growth, that there are other situations in which defaunation will be beneficial; and it is more likely to be detrimental to animal productivity. It remains to be determined whether manipulation of the types of ciliate protozoa in the rumen could improve animal performance. Information for this review was largely derived from comparisons of faunated and fauna-free animals. However, it is indicated that there are large differences in protozoa numbers and types between naturally faunated individuals in the same flock or herd, and that the effects of such variations on their host's nutrition are unknown. PMID- 3098728 TI - "Haemodialysis in lithium poisoning". PMID- 3098729 TI - Mutations that affect structure and assembly of light-harvesting proteins in the cyanobacterium Synechocystis sp. strain 6701. AB - The unicellular cyanobacterium Synechocystis sp. strain 6701 was mutagenized with UV irradiation and screened for pigment changes that indicated genetic lesions involving the light-harvesting proteins of the phycobilisome. A previous examination of the pigment mutant UV16 showed an assembly defect in the phycocyanin component of the phycobilisome. Mutagenesis of UV16 produced an additional double mutant, UV16-40, with decreased phycoerythrin content. Phycocyanin and phycoerythrin were isolated from UV16-40 and compared with normal biliproteins. The results suggested that the UV16 mutation affected the alpha subunit of phycocyanin, while the phycoerythrin beta subunit from UV16-40 had lost one of its three chromophores. Characterization of the unassembled phycobilisome components in these mutants suggests that these strains will be useful for probing in vivo the regulated expression and assembly of phycobilisomes. PMID- 3098730 TI - Genetic and morphological characterization of ftsB and nrdB mutants of Escherichia coli. AB - The ftsB gene of Escherichia coli is believed to be involved in cell division. In this report, we show that plasmids containing the nrdB gene could complement the ftsB mutation, suggesting that ftsB is an allele of nrdB. We compared changes in the cell shape of isogenic nrdA, nrdB, ftsB, and pbpB strains at permissive and restrictive temperatures. Although in rich medium all strains produced filaments at the restrictive temperature, in minimal medium only a 50 to 100% increase in mean cell mass occurred in the nrdA, nrdB, and ftsB strains. The typical pbpB cell division mutant also formed long filaments at low growth rates. Visualization of nucleoid structure by fluorescence microscopy demonstrated that nucleoid segregation was affected by nrdA, nrdB, and ftsB mutations at the restrictive temperature. Measurements of beta-galactosidase activity in lambda p(sfiA::lac) lysogenic nrdA, nrdB, and ftsB mutants in rich medium at the restrictive temperature showed that filamentation in the nrdA mutant was caused by sfiA (sulA) induction, while filamentation in nrdB and ftsB mutants was sfiA independent, suggesting an SOS-independent inhibition of cell division. PMID- 3098731 TI - Characterization of the motile hormogonia of Mastigocladus laminosus. AB - The cyanobacterium Mastigocladus laminosus produces motile hormogonia which move by gliding motility. These hormogonia were characterized in terms of their morphology, state of differentiation of the cells, optimal temperature for production and motility, minimal nutritional requirements to sustain motility, liberation of the hormogonium from its parental trichome, average surface velocity, and maximal concentration of agar through which the hormogonium may move. We found that an average hormogonium consisted of 13.6 cells of only the narrow-cell-type morphology. Gliding motility and the production of hormogonia were maximal at 45 degrees C. Agarose plus 0.20 mM Ca2+ was sufficient to sustain gliding motility. Hormogonia were liberated from the parental trichome by formation and lysis of a necridium. The average surface velocity of a hormogonium was 1.7 micron/s with a maximal velocity of 3 micron/s. Hormogonia were motile through 7% agar. Motile hormogonia leave a record of their passage in the form of easily visible tracks on the surface of solid media. Three types of tracks were observed: straight, sinusoidal, and circular. Normal, forward-directed motion involves screwlike rotation that describes a right-handed helix. However, observations are presented which suggest that rotational motion is not a prerequisite for gliding motility in this cyanobacterium. PMID- 3098732 TI - Characterization of the sacQ genes from Bacillus licheniformis and Bacillus subtilis. AB - The sacQ gene from Bacillus licheniformis was cloned and expressed in Bacillus subtilis. Deletion analysis shows that it encodes a 46-amino-acid polypeptide homologous to the B. subtilis sacQ gene product. The polypeptide, when it is overexpressed, activates the expression of a number of target genes in B. subtilis, all encoding secreted enzymes: alkaline protease, levansucrase, beta glucanase(s), xylanase, and alpha-amylase. The maximum stimulations measured for alkaline protease and levansucrase were by a factor of 70 and 50, respectively, when the sacQ gene from B. licheniformis was present on a multicopy plasmid in B. subtilis. The sacQ genes from B. subtilis and B. licheniformis, cloned in the same multicopy plasmid, were compared under the same conditions. The sacQ gene from B. licheniformis was more efficient than the sacQ gene from B. subtilis in producing the hypersecretion phenotype. The sacQ structural genes from B. subtilis and B. licheniformis were placed under the control of the same inducible promoter. Hypersecretion was specifically obtained under conditions of full induction of the promoter. The target site of levansucrase regulation by sacQ was identified as a 440-base-pair fragment located in the 5' noncoding region of sacB, suggesting transcriptional control. PMID- 3098733 TI - Purification and properties of saccharopine dehydrogenase (glutamate forming) in the Saccharomyces cerevisiae lysine biosynthetic pathway. AB - Saccharopine dehydrogenase (glutamate forming) of the biosynthetic pathway of lysine in Saccharomyces cerevisiae was purified 1,122-fold by using acid precipitation, ammonium sulfate precipitation, DEAE-Sepharose, gel filtration, and Reactive Red-120 agarose chromatography. The enzyme exhibited a native molecular size of 69,000 daltons by gel filtration and consisted of a single 50,000-dalton polypeptide based upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was readily denatured by exposures to temperatures exceeding 46 degrees C. The pH optimum for the reverse reaction was 9.5. The apparent Kms for L-saccharopine and NAD+ were 2.32 and 0.054 mM, respectively. The enzyme was inhibited by mercuric chloride but not by carbonyl or metal complexing agents. PMID- 3098734 TI - Characterization and mapping of the Bacillus subtilis prtR gene. AB - A gene from Bacillus natto encoding a 60-amino-acid peptide has been previously described that, when cloned on a high-copy plasmid in B. subtilis, enhances production of alkaline protease, neutral protease, and levansucrase. An identical gene was isolated from B. subtilis and caused a similar phenotype when placed on a high-copy plasmid. Genetic mapping localized this gene near metB, distant from other pleiotropic genes causing similar effects. Deletion of this gene from the B. subtilis chromosome had no obvious phenotypic effect. PMID- 3098735 TI - Construction and properties of an intracellular serine protease mutant of Bacillus subtilis. AB - An intracellular serine protease (ISP-1) mutant of Bacillus subtilis was created by introducing a frameshift into the coding region of the cloned gene. Intracellular protease activity in the mutant was very low, yet sporulation in both nutrient broth and minimal medium was normal. The rate of bulk protein turnover in the mutant was slightly slower than that in the wild-type strain. These results suggest that the gene for ISP-1 is not essential and that ISP-1 is not the major enzyme involved in protein turnover during sporulation. PMID- 3098736 TI - Inhibition by corrins of the ATP-dependent activation and CO2 reduction by the methylreductase system in Methanobacterium bryantii. AB - Corrins inhibited the ATP-dependent activation of the methylreductase system and the methyl coenzyme M-dependent reduction of CO2 in extracts of Methanobacterium bryantii resolved from low-molecular-weight factors. The concentrations of cobinamides and cobamides required for one-half of maximal inhibition of the ATP dependent activation were between 1 and 5 microM. Cobinamides were more inhibitory at lower concentrations than cobamides. Deoxyadenosylcobalamin was not inhibitory at concentrations up to 25 microM. The inhibition of CO2 reduction was competitive with respect to CO2. The concentration of methylcobalamin required for one-half of maximal inhibition was 5 microM. Other cobamides inhibited at similar concentrations, but diaquacobinamide inhibited at lower concentrations. With respect to their affinities and specificities for corrins, inhibition of both the ATP-dependent activation and CO2 reduction closely resembled the corrin dependent activation of the methylreductase described in similar extracts (W. B. Whitman and R. S. Wolfe, J. Bacteriol. 164:165-172, 1985). However, whether the multiple effects of corrins are due to action at a single site is unknown. PMID- 3098737 TI - Regulation of ligand-receptor dynamics by guanine nucleotides. Real-time analysis of interconverting states for the neutrophil formyl peptide receptor. AB - Intact neutrophils exhibit interconverting active and inactive receptor states with half-times for dissociation of 10 s and 2 min, respectively. We examined the effect of guanine nucleotides on ligand-receptor dynamics at 37 degrees C in neutrophils permeabilized with digitonin using continuous fluorometric measurements. The permeabilized cells exhibit a single class of slowly dissociating receptors with a half-time similar to the inactive state. The slowly dissociating state is lengthened in the presence of 10 mM by Mg2+ about two-fold but is relatively insensitive to substitutions of Na+ or K+. When guanine nucleotide is added the receptors dissociate uniformly with a half-time similar to the active state but are sensitive to the substitution of Na+ or K+ (K+ or K+/Mg2+ approximately 10 s; Na+ or Na+/Mg2+ approximately 4 s). When receptors in permeabilized cells are ADP-ribosylated with pertussis toxin the rapidly dissociating state is detected. In the presence of nonsaturating nucleotide or incomplete ribosylation, complex rates of ligand dissociation intermediate between the active and inactive forms are observed. Micromolar concentrations of Ca2+ block the effect of guanine nucleotide on the receptor. The relationships between ligand-receptor dynamics in intact neutrophils and interconverting states regulated by guanine nucleotides and ions in permeabilized cells are discussed. PMID- 3098738 TI - Channeling of extramitochondrial ornithine to matrix ornithine transcarbamylase. AB - In the presence of citrulline synthesis, we made the following observations. External ornithine is channeled between its transporter and ornithine transcarbamylase; mitochondria preloaded with cold ornithine, then incubated with [3H]ornithine, produced citrulline of the same specific radioactivity as that of external ornithine, while matrix ornithine remained essentially unlabeled. The channeling of ornithine suggests that some soluble enzymes are organized within the mitochondrial matrix. The rate of ornithine transport can be greater than 80 nmol/min/mg. At rates of carbamyl phosphate synthesis of 10-50 nmol/min/mg, the rate of citrulline synthesis is controlled by external ornithine in the range 0.03-0.2 mM; at greater than or equal to 0.2 mM ornithine, transport is not limiting for citrulline synthesis. At external ornithine concentrations less than or equal to 1 mM, i.e. within the physiological range, this amino acid is undetectable in the matrix. Given the rates of citrulline and urea synthesis which occur in vivo and the concentrations of ornithine present in the liver, our findings indicate that ornithine may contribute to the physiological regulation of urea synthesis. Preliminary reports of parts of this work have been published (Raijman, L., Cheung, C-W., and Cohen, N. S. (1984) Fed. Proc. 43, 1831; Cohen, N. S., Cheung, C-W., and Raijman, L. (1986) Fed. Proc. 45, 2677). PMID- 3098739 TI - Glycogenolytic, noninsulin-like effects of vanadate on rat hepatocyte glycogen synthase and phosphorylase. AB - Vanadate inactivated rat hepatocyte glycogen synthase and activated glycogen phosphorylase in a dose- and time-dependent manner. These effects were observed in hepatocytes from both fasted as well as fed rats. When rat hepatocytes were preincubated with [32P]phosphate and then with vanadate, and the 32P-labeled glycogen synthase was specifically immunoprecipitated, it was observed that vanadate stimulated the phosphorylation of the 88,000-dalton subunit of glycogen synthase. All of the phosphate was located in the same two CNBr fragments of the enzyme which are phosphorylated by glucagon and other glycogenolytic hormones. In cells incubated in a calcium-depleted medium, vanadate was still able to inactivate glycogen synthase but its effects on phosphorylase were essentially lost. These results demonstrate that, in the hepatocyte, vanadate exerts opposite effects than in the adipocyte and skeletal muscle, where vanadate has an insulin like action. PMID- 3098740 TI - Temporal aspects of O-glycosylation and cell surface expression of ascites sialoglycoprotein-1, the major cell surface sialomucin of 13762 mammary ascites tumor cells. AB - We have investigated the biosynthesis and cell surface expression of the major cell surface sialomucin (ascites sialoglycoprotein-1 (ASGP-1] of 13762 rat mammary ascites tumor cells by pulse or pulse-chase metabolic labeling combined with precipitation with peanut agglutinin and alkaline borohydride elimination or proteolytic fragmentation. The minimum time for initial glycosylation was estimated from the time required for the protein to acquire the ability to bind to peanut agglutinin to be less than 5 min. Moreover, when cells were labeled with threonine for 5 min and the ASGP-1 isolated by peanut agglutinin precipitation, 3% of the labeled threonine could be converted to 2-aminobutyric acid by alkaline borohydride elimination of the carbohydrate, indicating that at least 3% of the threonines of ASGP-1 are O-glycosylated within 5 min of polypeptide synthesis. The minimum time between the final glycosylation reactions in the cell and appearance of ASGP-1 at the cell surface was determined by trypsinizing galactose- or glucosamine-labeled cells at timed intervals after labeling to occur within 5-10 min of labeling. Both labeled glucosamine and galactosamine appeared in ASGP-1 fragments within 5 min, but the amount of labeled galactosamine was less than the amount of labeled glucosamine until after 20 min, when the 1:1 equilibrium ratio was reached. The half-time for appearance of glucosamine-labeled ASGP-1 at the cell surface was found to be greater than 4 h. The minimum time required from synthesis of the ASGP-1 polypeptide to appearance at the cell surface was determined by leucine labeling and proteolysis to be 70-80 min. These combined studies suggest a continuum of O-linked oligosaccharide initiation events extending over most of the period of ASGP-1 biosynthesis and transit from the endoplasmic reticulum to the cell surface. PMID- 3098741 TI - Induction of the hepatic mixed-function oxidase system by synthetic glucocorticoids. Transcriptional and post-transcriptional regulation. AB - Quantitative evaluation of transcriptional rates in isolated nuclei and intranuclear and cytoplasmic mRNA levels demonstrates that the catatoxic steroids pregnenolone-16 alpha-carbonitrile (PCN) and dexamethasone modulate microsomal drug metabolizing enzymes both positively and negatively at the transcriptional level. Additionally, a strong post-transcriptional influence, believed to be message stabilization, was found to be exerted by dexamethasone. Both NADPH cytochrome P-450b-homologous mRNA are induced 7- and 12-fold, respectively, presumably through message stabilization. Under these conditions, however, the oxidoreductase content of the cell is only marginally increased while the cytochrome P-450b level is actually decreased by 40% within three days after a single injection of dexamethasone. In contrast, genes coding for cytochromes P 450PCN show a definite increase in transcription following administration of either pre gnenolone-16 alpha-carbonitrile or dexamethasone, whereas transcription of the epoxide hydrolase gene is markedly reduced by administration of these compounds. PMID- 3098742 TI - Tau protein function in living cells. AB - Tau protein from mammalian brain promotes microtubule polymerization in vitro and is induced during nerve cell differentiation. However, the effects of tau or any other microtubule-associated protein on tubulin assembly within cells are presently unknown. We have tested tau protein activity in vivo by microinjection into a cell type that has no endogenous tau protein. Immunofluorescence shows that tau protein microinjected into fibroblast cells associates specifically with microtubules. The injected tau protein increases tubulin polymerization and stabilizes microtubules against depolymerization. This increased polymerization does not, however, cause major changes in cell morphology or microtubule arrangement. Thus, tau protein acts in vivo primarily to induce tubulin assembly and stabilize microtubules, activities that may be necessary, but not sufficient, for neuronal morphogenesis. PMID- 3098744 TI - Nuclear antigens follow different pathways into daughter nuclei during mitosis in early Drosophila embryos. AB - In the early embryonic development of Drosophila melanogaster, there is a series of 13 rapid and highly synchronous nuclear divisions. We have used a collection of monoclonal antibodies to follow the re-distribution of nuclear antigens into daughter nuclei at this developmental stage by indirect immunofluorescence microscopy. The antigens fall into several categories in terms of the pathways that are followed at mitosis. At one extreme is a group of antigens that remains continuously associated with the DNA throughout all the mitotic phases. At the other extreme, another group of antigens is excluded from the nucleus at prophase, and does not associate with the nucleus again until late telophase. One antigen, which becomes incorporated into the nucleolus at cellularization after the thirteenth division, becomes associated with the chromosomes during mitosis, but not until anaphase. Several different antibodies stain a diamond-shaped compartment that develops over the spindle at anaphase. The distribution of antigens within this spindle compartment shows some variation: one antigen appears to be present at higher concentrations in the central region of the spindle; others appear in three quite distinct areas corresponding to the positions of the new daughter nuclei and the old parental nucleus. Yet another antibody gives uniform staining of the spindle compartment. This antibody also recognizes a protein present in centrosomes. PMID- 3098743 TI - Micromanipulated bivalents can trigger mini-spindle formation in Drosophila melanogaster spermatocyte cytoplasm. AB - Single (individual) bivalents in cultured Drosophila melanogaster primary spermatocytes were detached from the spindle with a micromanipulation needle and placed in the cytoplasm. Such bivalents are prevented from rejoining the spindle by a natural membrane barrier that surrounds the spindle, but they quickly orient as if on a spindle of their own and the half-bivalents separate in anaphase. Serial section electron microscopy shows that a mini-spindle forms around the cytoplasmic bivalent, i.e., the microtubule density in the vicinity of the bivalent is much greater than in other cytoplasmic regions. This microtubule population cannot be accounted for solely by kinetochore nucleation and/or capture of microtubules. Furthermore, the mini-spindles frequently form at odd angles to the main spindle, so that at least one pole has no relationship to the poles of the main spindle. We conclude that a bivalent, or factors that become associated with the bivalent as a result of the manipulation, can either stabilize microtubules or promote their assembly. The bivalent activates latent microtubule organizing centers, or alternatively, polar organizing material has been passively transported from the main spindle to the cytoplasm by the micromanipulation procedure. PMID- 3098745 TI - Chemokinetic behaviour of insect haemocytes in vitro. AB - Time-lapse microphotography was used to film the locomotory behaviour of cockroach haemocytes in vitro, and the cell tracks were analysed for speed and persistence; the percentage mobilization and the diffusion rate of the population were calculated. Haemocytes are either fast locomotor or spread moving cells, or non-motile spread or rounded cells; the first three types are plasmatocytes and their behaviour is interchangeable. Approximately 20% of the cells are motile under control conditions and there is no correlation between orthokinesis and klinokinesis. If activated haemocyte lysate supernatant (HLS), a source of components of the prophenoloxidase enzyme sequence, is added to the cell monolayer, up to 80% of the cells switch to fast locomotor behaviour, rounding up and moving faster and for longer in straight lines. Neither heat-inactivated HLS nor zymosan supernatant, used to activate HLS, had any effect. If the chemokinins present in activated HLS are also released in vivo on haemocyte activation or during cuticular wounding, then they and the induced changes in haemocyte adhesion could contribute to haemocyte recruitment to sites of infection. PMID- 3098747 TI - Disabling dyspnea of sudden onset. PMID- 3098746 TI - Effect of preischemia cyclooxygenase inhibition by zomepirac sodium on reflow, cerebral autoregulation, and EEG recovery in the cat after global ischemia. AB - Zomepirac sodium (ZS) (5 mg/kg i.v.) was used to evaluate the effects of preischemia cyclooxygenase inhibition on CBF (as assessed by 133Xe clearance), CBF-PaCO2 responsiveness, and electrophysiologic (EEG) parameters before and after a 15-min period of complete global ischemia produced by four-vessel occlusion and mild hypotension. During the 15-min period of ischemia, CBF was essentially zero. Following reflow all groups displayed an initial hyperemia as compared with control (92 +/- 11 vs. 141-146 ml/100 g/min). Saline-treated animals during reflow displayed a delayed hypoperfusion (26 +/- 3 ml/100 g/min), which showed no improvement during the 2-h reflow period prior to death. In contrast, ZS-treated animals during reflow displayed significantly higher flows during the hypoperfusion phase (72 +/- 9 ml/100 g/min). The CBF-PaCO2 response displayed an approximately sevenfold reduction in slope at 2 h after reflow in saline-treated animals. This decrease in PaCO2 reactivity was not observed in the ZS-pretreated animals. With regard to EEG, all animals showed a total flattening during the 15 min of ischemia. In saline-treated animals only one of seven showed any sign of even marginal recovery. In ZS-treated animals EEG activity showed prominent recovery in seven of seven. Brainstem auditory evoked potentials were monitored and showed prominent recovery of amplitude and latency in ZS but not saline-treated animals during reflow. PMID- 3098748 TI - Pneumonia complicated by bacteremia: therapeutic options. PMID- 3098749 TI - AIDS: medical ethics grand rounds. PMID- 3098750 TI - Segmental mastectomy incision options. PMID- 3098751 TI - Xylocaine treatment for acute herpes zoster. PMID- 3098752 TI - Ascites, cirrhosis, and congestive heart failure. PMID- 3098753 TI - 'Sugar in urine' in routine test of healthy teenage boy. PMID- 3098754 TI - Uses of acupuncture for pain relief. PMID- 3098755 TI - An autopsy of the clinical reasoning process. PMID- 3098756 TI - Irregular tachycardia and cardiovascular collapse. PMID- 3098757 TI - Falls and hip fracture in the elderly. PMID- 3098758 TI - Management of localized prostate cancer. PMID- 3098759 TI - Hypercoagulable states and venous thrombosis. AB - Many factors predispose patients to thromboembolic disease. A young person presenting with idiopathic deep venous thrombosis may never have its etiology elucidated, despite exhaustive testing. On the other hand, hypercoagulability is no mystery in an obese, bedridden, postoperative patient with a malignancy. Invasive or noninvasive testing should be performed in all suspicious cases. Patients with positive results should be treated promptly; those with negative findings should not be subjected to anticoagulation. The length of anticoagulation depends on the length of time the patient remains at risk of thrombosis and may vary from months to a lifetime. Patients over 40 should receive prophylactic minidose heparin for abdominal and thoracic surgery. Patients undergoing hip surgery require some form of anticoagulation--be it heparin, warfarin, aspirin, or dihydroergotamine-heparin. Because of lower morbidity and superior long-term efficacy, transvenous devices are favored over surgical techniques for inferior vena caval interruption. PMID- 3098760 TI - Acute and chronic liver disease in a young homosexual man. PMID- 3098761 TI - HLA genes and predisposition to rheumatic diseases. PMID- 3098762 TI - Influenza and its complications. Recognition and prevention. PMID- 3098763 TI - The physiology of articular stress: osteoarthrosis. PMID- 3098764 TI - Echocardiography in ventricular and valvular disease. II. PMID- 3098765 TI - Etiologies and management of potassium deficiency. PMID- 3098766 TI - Alzheimer's disease: an age-old problem. PMID- 3098767 TI - Leaving no stone unturned. PMID- 3098768 TI - Calcium antagonists and the kidney. PMID- 3098769 TI - Gas chromatographic separation of 2,3,7,8-tetrachlorodibenzo-p-dioxin from polychlorinated biphenyls and tetrachlorodibenzo-p-dioxin isomers using a polymeric liquid crystal capillary column. PMID- 3098770 TI - Luteal responses to gonadotropin-releasing hormone during the luteal phase: relation to the age of corpus luteum. AB - The pituitary and luteal responsiveness of GnRH were studied in 20 normal women at different stages of the luteal phase (LP). Blood samples were collected every 15 min for 180 min before and 120 min after the iv injection of 25 micrograms GnRH. The studies were performed in the early LP (ELP; days 2-3 of LP; n = 5), mid-LP (MLP: days 4-8 of LP; n = 11), late LP (LLP; days 9-12 of LP; n = 13), and premenstrual phase (PMP; days 13-14 of LP; n = 3). Plasma LH, FSH, progesterone (P), and estradiol (E) levels were assayed by RIA. The data were analyzed as integrated secretory area before (ISAb) and after GnRH stimulation (ISAs) and in terms of their percent increase with respect to the basal value. In all studies, GnRH elicited increases in plasma LH and FSH (P less than 0.001). On the other hand, in the ELP, GnRH did not alter steroid ISAs compared to their ISAb, while significant increases in plasma P and E levels were found in the MLP (P, P less than 0.01; E, P less than 0.02) and LLP (P and E, P less than 0.01). In the PMP, two women had no increase in steroid secretion; in the remainder of the subjects, both P and E ISAs markedly increased. This different pattern was not related to basal steroid levels. All women who had a blunted steroid response in the ELP or PMP had a normal secretory response of both P and E when studied at the other LP stages of the same cycle. Furthermore, there was a positive linear correlation between plasma P and E for the ISAb and ISAs values, while the secretory patterns of gonadotropins and steroids were not related to each other. In conclusion, the corpus luteum is able to respond to GnRH to GnRH at a well identified period of the LP. This pattern indicates variable dependence of the corpus luteum on the functional activity of the hypothalamic-pituitary axis. PMID- 3098772 TI - Human corticotropin-releasing hormone in man: dose-response of minute ventilation and end-tidal partial pressures of carbon dioxide and oxygen. AB - The respiratory stimulant properties of iv injections of 33, 67, and 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) were studied in 12 normal men in a single blind, placebo-controlled trial. All doses of hCRH induced a respiratory stimulation in every subject, and the stimulation was dose dependent. The onset of respiratory stimulation occurred within 15-30 sec after hCRH infusion was started. Initially, there was an increase in tidal volume (VT), followed by an increase in respiratory rate. The maximum minute ventilation (VE) occurred 60-120 sec after starting the injection. The 33-micrograms hCRH dose induced a 35% increase in VE from 6.3 +/- 0.6 (+/- SD) to 9.7 +/- 1.3 liters/min (P less than 0.001) due to a marked increase in VT from 531 +/- 105 to 688 +/- 142 ml (P less than 0.001) and only a slight increase in the respiratory rate from 12.4 +/- 3.0 to 14.3 +/- 3.1 breaths/min (P less than 0.001); heart rate was not altered at this dose. The 100-micrograms hCRH dose increased the VE by 81% to 11.5 +/- 1.5 liters/min, mainly due to an increase in VT. VE was elevated for 5.8, 7.2, or 8.3 min after the end of injection of the three hCRH doses. Increases in VE markedly lowered the end-tidal partial pressure of carbon dioxide (P(ET)CO2; nearly identical with the arterial PCO2 in normal subjects). hCRH (33 micrograms) lowered P(ET)CO2 from 40.3 +/- 1.2 to 37.2 +/- 1.9 mm Hg (P less than 0.001), and 100 micrograms hCRH lowered P(ET)CO2 to 33.4 +/- 1.2 mm Hg. End-tidal partial pressure of oxygen, i.e. the most sensitive parameter for the duration of action of respiratory stimulation, was elevated for 8.5, 10.2, and 14 min after injection of 33, 67, or 100 micrograms hCRH. Sixty-seven micrograms of hCRH was the lowest effective dose for an increase in the heart rate (from 66.4 to 79.0 beats/min; P less than 0.001), and 100 micrograms hCRH markedly increased the heart rate by 20% to a peak value of 83.5 beats/min. Heart rate increased within 90 sec and returned to the control value after 5-10 min. These data suggest that hCRH is a rapidly acting, dose-dependent, and potent respiratory stimulant. Since this hyperventilatory effect of hCRH occurred in every subject after all doses tested, respiratory stimulation may represent specific biological activity of CRH rather than a side-effect. PMID- 3098771 TI - The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: clinical and laboratory correlations. AB - Several lines of evidence indicate that hypothalamic-pituitary-gonadal activity varies among men with idiopathic hypogonadotropic hypogonadism (IHH). To test the hypothesis that a spectrum of abnormalities of GnRH secretion underlies the syndrome of IHH, we characterized the patterns of GnRH-induced gonadotropin secretion during periods of frequent sampling in 50 consecutive men with IHH and contrasted them with those in 20 normal men. The largest group of IHH patients (n = 42) had no detectable LH or FSH pulsations and could be categorized into 2 subsets according to the presence or absence of evidence of spontaneous puberty. The most severely affected subset (n = 32), who recalled no history of puberty, had testes with a mean volume of 3.3 +/- 0.5 (+/- SEM) ml, with a prepubertal appearance on biopsy, and often were anosmic (n = 17). The second subset of apulsatile IHH men (n = 10) had histories of partial or complete spontaneous sexual development with subsequent isolated loss of sexual function, testes with a mean volume of 13.3 +/- 1.9 ml (P less than 0.01 compared to the first subset), a pubertal or adult appearance of the testes on biopsy, and an intact sense of smell. In a second group of IHH patients (n = 3), LH was secreted predominantly in a nighttime pattern similar to that of normal children during early puberty. These men were aged 18-24 yr, had a mean testicular volume of 10.5 +/- 2.3 ml, pubertal changes on testicular biopsy, and an intact sense of smell. A third group of IHH men (n = 4) had LH pulses of abnormally low amplitude. Only one patient in this group had a history of spontaneous sexual development. The mean testicular volume of these patients was 5.6 +/- 1.9 ml, and the testes appeared prepubertal (n = 3) or pubertal (n = 1) on biopsy. In addition to these groups, another patient had apparent LH pulsations and nearly normal amplitude, but the LH was bioinactive and appeared to consist chiefly of alpha-subunit. Testing of other anterior pituitary hormone functions did not distinguish IHH men from normal men. However, those IHH patients with some evidence of endogenous GnRH secretion had higher basal and stimulated serum PRL levels than IHH men without such evidence (P less than 0.05), suggesting an influence of GnRH on PRL secretion. PMID- 3098773 TI - Acromegaly due to a growth hormone-releasing hormone-secreting bronchial carcinoid tumor: further information on the abnormal responsiveness of the somatotroph cells and their recovery after successful treatment. AB - We studied GH secretion in a patient with acromegaly and a bronchial carcinoid tumor before and again after surgical removal of this tumor. Before removal of the carcinoid tumor, plasma GH increased slightly after glucose loading (OGTT) and markedly after TRH (650%) and insulin (440%) treatment. Plasma GH did not change after GH-releasing hormone (GHRH), LHRH, or L-dopa administration. Somatostatin (SRIH) infusion lowered plasma GH. No change in plasma immunoreactive GHRH (IR-GHRH) occurred after TRH, glucose, insulin, or SRIH administration. Two weeks after removal of the carcinoid tumor, TRH induced GH secretion (250%) when the IR-GHRH level was undetectable and somatomedin-C was within normal limits. Fifteen weeks after surgery, the patient had normal GH secretion. IN CONCLUSION: no pattern of GH secretion is diagnostic of acromegaly due to ectopic GHRH secretion, but the lack of GH response to exogenous GHRH and a large response during hypoglycemia may be features of this condition. When acromegaly and abnormal GH responsiveness are induced by a GHRH-secreting tumor, the increases in plasma GH after TRH, glucose, and insulin administration are not mediated by GHRH. After removal of the GHRH-secreting tumor, persistent paradoxical GH response to TRH does not require abnormally high IR-GHRH levels and does not preclude complete recovery. PMID- 3098774 TI - Isolated prolactin deficiency in a woman with puerperal alactogenesis. AB - Idiopathic PRL deficiency was detected in a parturient woman with otherwise normal pituitary function. This PRL disorder first became manifest postpartum when she had no milk production, and oral metoclopramide failed to raise her serum PRL levels. Her second pregnancy occurred spontaneously after 3 yr of attempts to conceive. During the pregnancy, her serum PRL concentration was very low, varying from 4.5-7.8 ng/ml, and the puerperium was again characterized by alactogenesis. During normal menstrual cycles and after iv GnRH, TRH, metoclopramide, and insulin tolerance tests, serum PRL was only rarely detectable by RIA, at very low concentrations. Bioassay results confirmed the PRL deficiency. The results confirm that PRL is necessary for puerperal lactation and suggest that it is needed for normal ovarian function. The present data also suggest that the maternal pituitary is the main source of serum PRL during pregnancy, and the decidua has only a minor contribution in this respect. PMID- 3098775 TI - Gonadotropin and thyrotropin alpha- and beta-subunit gene expression in normal and neoplastic tissues characterized using specific messenger ribonucleic acid hybridization probes. AB - The glycoprotein hormones consist of a common alpha-subunit and distinct, but structurally related, beta-subunits which confer biological specificity. To study glycoprotein hormone gene expression, we prepared specific oligonucleotides complementary to nonhomologous regions of the alpha-subunit and each of the beta subunit mRNAs encoding human LH, CG, TSH, and FSH. beta-Subunit mRNAs were expressed at relatively low levels in normal pituitary tissue, but were found in greater amounts in pituitary gonadotroph and thyrotroph adenomas. The lengths of the glycoprotein hormone alpha- and beta-subunit mRNAs in normal and neoplastic pituitary tissue were indistinguishable. Expression of different members of the closely related LH beta/CG beta gene family were examined in normal and neoplastic pituitary and placenta using short oligonucleotides complementary to nonhomologous regions of the genes. Although CG beta mRNA was found previously in a pituitary adenoma, none was detected in normal pituitary tissue. In placenta, there was abundant expression of the CG beta gene, but no expression of the LH beta gene, consistent with the acquisition of tissue-specific regulatory sequences in the recently evolved upstream promoter recognition site of the CG beta gene. Primer extension analysis of CG beta mRNA indicated that the same CG beta gene promoter site was used in both normal placenta and JEG-3 choriocarcinoma cells. Of the two CG beta genes that have been reported to be functional, CG beta gene 5 was preferentially expressed in both normal placenta and the neoplastic JEG-3 cell line. CG beta gene 3 expression accounted for only about 5% of the total CG beta mRNA. The previously uncharacterized human TSH beta and FSH beta mRNAs were studied in normal and neoplastic pituitary tissue. At least two species of FSH beta mRNA were found on Northern blots. Oligonucleotide primed extension of pituitary mRNA demonstrated that FSH beta mRNA heterogeneity resulted from transcription from distinct promoter sites, encoding 5' untranslated tracts of 48 and 83 bases. These studies demonstrate that specific oligonucleotide probes distinguish expression of the structurally related glycoprotein hormone beta-subunit mRNAs, allowing analyses of tissue-specific gene expression under different physiological conditions as well as in normal and neoplastic tissues. PMID- 3098776 TI - Hyperthyroxinemia due to the coexistence of two raised affinity thyroxine-binding proteins (albumin and prealbumin) in one family. AB - The T4-binding proteins of a euthyroid subject with persistent hyperthyroxinemia (T4, greater than 20 micrograms/dl) were present in normal concentrations. Abnormal transport of both T4 and rT3 was demonstrated by reverse flow paper electrophoresis; excess T4 was bound to albumin and prealbumin, while increased binding of rT3 was confined to prealbumin. The three T4-binding proteins in the serum of the subject were isolated by affinity chromatography and characterized. Equilibrium dialysis experiments demonstrated a 20-fold increase in affinity of the albumin for T4 (Ka, 5.1 X 10(6) M-1) and a 4-fold increase in affinity of prealbumin for T4 (Ka, 3.0 X 10(8) M-1); T4-binding globulin affinity was normal. Nine other members of the family were also studied. Two sisters of the propositus have both the abnormal albumin and the variant prealbumin, while a brother has normal T4-binding proteins. The mother has the abnormal albumin alone. The father, his sister, and one of his three brothers have the variant prealbumin only. Despite the presence of the variant prealbumin in some of the paternal relatives of the propositus, their total iodothyronine concentrations were within the normal ranges; the condition may, therefore, often go undetected. The characteristics of the albumin found in the affected members of this kindred are those we have defined for familial dysalbuminemic hyperthyroxinemia type I, which is inherited as an autosomal dominant trait. The pattern of inheritance of the variant prealbumin is also consistent with a dominant mode with strong penetrance. The presence of two separately inherited abnormal T4 transport proteins in the same family suggests that both conditions may be more common than has been thought. PMID- 3098777 TI - Antibody response to teichoic acid and peptidoglycan in Staphylococcus aureus osteomyelitis. AB - An enzyme-linked immunosorbent assay was used to evaluate the immunoglobulin G (IgG) response to Staphylococcus aureus crude teichoic acid (TA) and peptidoglycan (PG) in both rabbits and patients with osteomyelitis. In rabbits with experimental S. aureus osteomyelitis, elevated levels of IgG to TA were present in 13/18 (72%) of the serum samples obtained at 4 and 10 weeks postinfection. In contrast, only 5/18 (28%) of these sera were found to be positive for antibodies to PG. Of a total of 39 patients with confirmed S. aureus osteomyelitis (11 acute, 28 chronic), IgG to TA was elevated in 17 (44%), whereas antibodies to PG were found to be increased in only 1 (3%). Cross-reacting antibodies to S. aureus TA were detected in only 1/18 (6%) of the patients with osteomyelitis caused by organisms other than S. aureus. These studies indicate that IgG to TA is more prevalent than IgG to PG in patients with staphylococcal osteomyelitis. Although these results are encouraging, a larger number of patients is required for an adequate evaluation of the TA enzyme-linked immunosorbent assay for the diagnosis and management of suspected S. aureus osteomyelitis. PMID- 3098778 TI - Antigenuria in infants with acute and congenital Chagas' disease. AB - Detection and partial characterization of Trypanosoma cruzi soluble antigens (SAg) in urine, as well as demonstration of parasite circulating antigens (CAg) in serum from pediatric patients with acute (10 patients) and congenital (10 patients) Chagas' disease, are reported. Classical techniques for parasite detection and antibody serology were also conducted in both groups. Samples collected before the onset of parasiticidal drug treatment were tested by an enzyme-linked immunosorbent assay for SAg and CAg demonstration. The control population consisted of 6 children with acute toxoplasmosis, 6 with cutaneous leishmaniasis, and 20 healthy individuals. Patients with acute cases were 100% positive for both SAg and CAg, whereas patients with congenital disease were 80% CAg positive and 100% SAg positive. Controls yielded negative results in all cases. Partial characterization of SAg from two patients with acute disease was performed by iodination, affinity chromatography, immunoprecipitation, and two dimensional gel electrophoresis. Two different antigenic glycoproteins (80 kilodaltons, pI 6 to 6.5 and 55 kilodaltons, pI 6.5 to 7) were identified by these methods. Traditional serology and classical parasitologic tests failed, each in a different way, to provide an accurate diagnosis in the total of our patients. The enzyme-linked immunosorbent assay for SAg detection proved to be the most effective procedure for achieving early and precise proof of infection in acute and congenital cases of Chagas' disease. PMID- 3098779 TI - Quality control limits for microdilution susceptibility tests with norfloxacin. AB - A multilaboratory study was designed to define quality control limits for microdilution susceptibility tests with norfloxacin. The following limits were proposed: for Escherichia coli ATCC 25922, 0.03 to 0.125 micrograms/ml; for Pseudomonas aeruginosa ATCC 27853, 1.0 to 4.0 micrograms/ml; for Staphylococcus aureus ATCC 29213, 0.5 to 2.0 micrograms/ml; and for Streptococcus faecalis ATCC 29212, 2.0 to 8.0 micrograms/ml. The latter represents a change in the previously recommended control limits. PMID- 3098781 TI - Ectopic bone formation in children and adolescents with head injuries: its management. AB - During an 11-year prospective study at Kennedy Memorial Hospital for Children (Brighton, MA), ectopic bone formation occurred in 22 of 145 children and adolescents admitted in coma following head injury. Subsequent deformities and limitation of motion were an impediment to rehabilitation in 15 of these patients, who recovered from the coma. Several bone excision procedures, either alone or in conjunction with other physical and/or pharmacological modes of treatment, were followed by recurrence of ectopic bone until salicylates were used. The latter eliminated or minimized recurrence of ectopic bone. The study suggests a useful role for salicylates not only in preventing recurrence, but also in minimizing the occurrence of ectopic bone formation in these patients. PMID- 3098780 TI - Production, characterization, and species specificity of five monoclonal antibodies to Mycobacterium tuberculosis. AB - The production and characterization of five monoclonal antibodies to Mycobacterium tuberculosis are described. Specificity of the monoclonal antibodies was tested against other mycobacterial species by an enzyme-linked immunosorbent assay and immunoblots. HGT 3a, an immunoglobulin M (IgM) antibody, recognizes a molecule of 38,000 molecular weight present only in the tuberculosis complex of M. tuberculosis and Mycobacterium bovis BCG. HGT 6, an IgG1 antibody, recognized two molecules with molecular weights of 43,000 and 45,000 and showed limited cross-reactivity. Three other antibodies, HGT 1, HGT 2, and HGT 4, all belonging to the IgG1 type, recognized multiple bands and showed broad reactivity among all mycobacterial antigens tested, Escherichia coli and Nocardia asteroides. PMID- 3098782 TI - Exaggerated atrial arachidonate metabolism in rabbit left ventricular myocardial infarction. AB - Isolated perfused rabbit hearts that have previously been subjected to in vivo left ventricular myocardial infarction respond to N-formylmethionyl-leucyl phenylalanine (fMLP) or bradykinin (BK) administration with the synthesis of large quantities of eicosanoids. To anatomically localize these synthetic responses we studied the effects of fMLP and BK on eicosanoid synthesis in isolated atria and isolated perfused ventricles from normal and infarcted (4 d in vivo) rabbit hearts. These studies revealed that enhanced agonist-stimulated eicosanoid synthesis occurs largely in the right atria of infarcted hearts, a site distant from the zone of injury. Studies of exogenous arachidonate metabolism in microsomes prepared from various regions of the heart showed that while prostaglandin synthetic capacity is preferentially localized to the right atrium, right atria from normal and infarcted hearts have similar thromboxane and PGE2 synthetic capacity. These results demonstrate that enhanced agonist stimulated eicosanoid synthesis following rabbit left ventricular myocardial infarction occurs largely in the right atrium, and that this effect is independent of the activity of prostaglandin synthetic enzymes. PMID- 3098783 TI - Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro. AB - Pseudomonas aeruginosa culture filtrates varied in their ability to slow human ciliary beat frequency (7-71%). This activity did not correlate with known virulence factors. However, a close correlation (r = 0.97) existed between ciliary slowing and pigment content. In a prolonged culture, the increase in activity correlated (r = 0.94) with pigment accumulation. Gel filtration of lyophilized filtrate yielded a single peak of activity corresponding to the pigment fraction. Pyocyanin extracted from an active strain, and 1 hydroxyphenazine were purified by high performance liquid chromatography, and characterized by ultraviolet absorbance spectra and mass spectrometry. Both slowed cilia in a dose-dependent manner, and were synthesized and shown to be indistinguishable from the biological compounds. Pyocyanin caused gradual onset of slowing and ultimate widespread ciliostasis with epithelial disruption. 1 hydroxyphenazine caused rapid onset of ciliary slowing associated with dyskinesia and ciliostasis. Pyocyanin assayed within filtrates accounted for a significant proportion of the bioactivity present. PMID- 3098784 TI - Enhancement of natural killer function through activation of the T11 E rosette receptor. AB - Natural killer (NK) cells, which represent a small fraction of normal peripheral blood mononuclear cells, were purified by immunofluorescent cell sorting of NKH1+ cells. cytotoxicity of NKH1+ cells could be enhanced through activation by monoclonal antibodies (anti-T11(2) and anti-T11(3)) specific for epitopes of the sheep erythrocyte receptor or by recombinant interleukin-2 (rIL-2). After 18 h, incubation with both anti-T11(2/3) and rIL-2 resulted in similar levels of enhanced cytotoxicity against NK-resistant as well as NK-sensitive targets. Before and after induction, cytotoxicity was found predominantly within the NKH1+ population. These results suggest that several distinct mechanisms may be capable of enhancing NK activity and that the cells responsible for lymphokine-activated killing are likely to be the same population capable of spontaneous or natural killing before activation in vitro. PMID- 3098786 TI - A composite three-dimensional echocardiographic technique for left ventricular volume estimation in children: comparison with angiography and established echographic methods. AB - A composite three-dimensional (3D) echographic left ventricular (LV) reconstruction to measure LV volumes was evaluated in 26 children. Four apical views, to minimize assumptions about LV shape, were used to obtain a "wire-cage" model of the LV in 3D. Numerical integration was used to make estimates of both end-diastolic and end-systolic volumes. Volume estimates obtained with echographic techniques and those obtained with the angiographic biplane method were compared. The echographic volume estimates were systematically smaller (p less than 0.005), and a consistent trend, though not significant, was observed indicating that this systematic error is less for the 3D method. One-way analysis of variance confirmed significant global geometric fluctuations. Hence, 3D reconstruction can be performed in a clinical setting, and the enhanced graphic representation of global LV geometry may contribute to improved patient management. PMID- 3098785 TI - Regulation of sodium absorption by canine tracheal epithelium. AB - To regulate the quantity of respiratory tract fluid, the airway epithelium either secretes chloride, Cl-, or reabsorbs sodium, Na+. Many secretagogues inhibit Na+ absorption, but the decrease may result from a fall in the electrochemical gradient for Na+ absorption. We examined regulation of Na+ absorption independent of Cl- secretion, by bathing canine tracheal epithelium in Cl--free, gluconate Ringers solution. Prostaglandin E2, 2-chloroadenosine, and isoproterenol increased short-circuit current (Isc) and the rate of Na+ absorption. In contrast, indomethacin, which inhibits endogenous prostaglandin production, decreased Isc. These agents regulate cellular levels of cAMP; direct addition of 8-Br-cAMP also acutely increased Isc. We examined chronic regulation of Na+ absorption in cell monolayers grown on permeable supports in serum-free media. Exposure to aldosterone for two days increased baseline Isc by 50% and the amiloride-inhibitable current by 55%. These data indicate that Na+ absorption is both acutely and chronically regulated in the airway epithelium. PMID- 3098788 TI - Biparietal diameter and menstrual age in the black population attending Edendale Hospital. AB - The relationship between fetal biparietal diameter measured by echography and menstrual age for blacks was studied. Predicted values and their confidence limits are presented in tables and graphs. The biparietal diameter was significantly smaller from 28 weeks than American and European studies, demonstrating that a composite graph was not applicable to the Zulus. The echographic results were checked at term by external cephalometry. Occipitofrontal circumference and birth weights for newborns were found similar to other studies. The smaller BPD in late pregnancy could be explained by the head's shape. The new charts are valuable in assessing fetal growth in African blacks. PMID- 3098787 TI - Ultrasound evaluation of uncomplicated and complicated acute viral hepatitis. AB - Seven hundred ninety-one consecutive patients with acute viral hepatitis, 17 of whom had liver failure, and 97 healthy volunteers were examined by ultrasound. No specific patterns were found in either the uncomplicated or the complicated forms. Only 19 subjects showed a typical "bright liver" pattern, which is correlated with significant vacuolar hepatocellular degeneration. The increased brightness and clear visualization of portal vein radicle walls, previously described in this disease, were detected in only 32.2% of the hepatitis patients but were also seen in 30.9% of the normal controls. PMID- 3098789 TI - Utility and limitations of splanchnic venous ultrasonography in diagnosis of portal hypertension. AB - The splanchnic venous system was examined by real-time ultrasonography in 46 patients with cirrhosis and documented portal hypertension and in 32 healthy subjects. Patients with portal hypertension had increased diameter of the splanchnic (portal, splenic, and superior mesenteric) veins (76% of patients), attenuation of the normal inspiratory increase in vein size (59%), and demonstrable portasystemic collateral vessels (umbilical or coronary veins or spontaneous splenorenal shunt) (44%). Splanchnic venous dimensions were significantly increased and changed less with respiration in patients with demonstrable portasystemic collaterals as compared to patients without these vessels. Portal pressure correlated only mildly with portal vein diameter (r = 0.30, p less than 0.05). Ultrasound abnormalities are present in a majority of patients with intrahepatic portal hypertension. However, because increased venous diameter and attenuated change in diameter with respiration are less frequent in patients lacking demonstrable portasystemic collaterals, the sensitivity of the test is least in those patients in whom its specificity is also limited. PMID- 3098790 TI - Left lobe of the liver mimicking perisplenic collections. AB - Three patients were scanned in whom the sonographic diagnoses of perisplenic fluid collections were made. Computed tomography scanning demonstrated that the appearances were not caused by perisplenic pathology but by lateral extent of normal left lobe of the liver. Methods to avoid this potential sonographic pitfall are suggested. PMID- 3098791 TI - Antenatal sonographic diagnosis of congenital clubfoot: a possible indication for amniocentesis. AB - Eighteen cases of congenital clubfoot were diagnosed sonographically between 16 and 38 weeks. The method of diagnosis, associated anomalies, karyotypes, and obstetric outcomes are described. Fifteen of the 18 fetuses had other major congenital anomalies, and of these, four had abnormal karyotypes. Only three had uncomplicated clubfoot as the only abnormality. Because of the significant incidence of abnormal karyotypes in our series, confirmed in other reported cases, identification of a clubfoot on prenatal sonography may be considered an indication for amniocentesis, particularly when other anomalies are present. PMID- 3098792 TI - Echocardiographic follow-up in Marfan's syndrome: mitral, tricuspid, and aortic valve prolapse with calcification of patent foramen ovale. PMID- 3098793 TI - Real-time ultrasound diagnosis of internal jugular vein thrombosis. PMID- 3098794 TI - Prenatal diagnosis of reversible cardiac hypoplasia associated with congenital diaphragmatic hernia: implications for postnatal management. PMID- 3098795 TI - Fatal diphenylhydantoin-induced hepatic necrosis: sonographic-pathologic correlation. PMID- 3098796 TI - Dermoid tumor and cystadenoma arising in the same ovary. PMID- 3098797 TI - Carotid artery aneurysm diagnosed by duplex scanning. PMID- 3098798 TI - Combined perineal-abdominal sonography in the evaluation of vaginal atresia. PMID- 3098799 TI - Newborn with hydrometrocolpos and ambiguous genitalia: clinical significance. PMID- 3098800 TI - New technique for myocardial contrast echocardiography in the experimental canine model using a special cannula for selective left main coronary artery cannulation. PMID- 3098802 TI - Novel method for detecting micro-organisms in blood cultures. AB - A method for detecting the growth of micro-organisms in blood culture by a visual signal is described. The system utilises a single blood culture medium that has been specifically formulated to support growth of aerobic, anaerobic, and microaerophilic micro-organisms. The system is based on the principle that when micro-organisms grow in the medium in a sealed bottle their metabolic products create positive pressure. This positive pressure displaces the infected blood and broth into an upper chamber, which acts as a visual signal of microbial activity. All the test micro-organisms, when inoculated at less than 20 colony forming units into simulated human blood cultures, gave a positive signal. PMID- 3098801 TI - In vitro stimulation of plasminogen activator release from vein walls by adrenaline. AB - The effect of adrenaline on plasminogen activator release was studied in vitro in human vein biopsy specimens, in which the fibrinolytic activity was determined according to the fibrin slide technique. The tissue slides were covered with a thin fibrin film containing 10(-9) and 10(-7) M adrenaline and exposed for 30 to 60 minutes. In both concentrations highly significant (p less than 0.001) enhancement of fibrinolytic activity was shown, and the enhancement of fibrinolysis was most pronounced during the first 30 minutes of exposure. Stimulation of fibrinolysis was maximal after exposure to the physiological concentration of 10(-9) M, while no further increase was seen using the pharmacological concentration. These results show that adrenaline has a stimulant effect on tissue fibrinolysis in vitro, and this effect may account for the direct stimulation of fibrinolysis by adrenaline in vivo. PMID- 3098803 TI - Economic perspectives on diagnosis and treatment planning in periodontology. AB - Economic factors in diagnosis and treatment planning in periodontology may be considered from several points of view. A first perspective is that of government responsibility. Because of the explosion in health care expenditure in the last decade, public funding of dental care programmes may become static or even reduced. Most governments try to curb the ever growing public health expenditure. Consequently, terms like effectiveness, efficiency and accountability are now becoming common words also in relation to periodontal health care. Moreover, private insurance companies, which have entered this area, may be individual patient who, explicitly or implicitly, would like to consider the services individual patient, who explicitly or implicitly, would like to consider the services rendered in periodontal therapy and prevention as cost-effective. Features of supply of and demand for care on an individual basis should also be considered. Finally, the periodontist or general practitioner has to consider economic factors. In professional life, there should be a balance between good working conditions providing satisfactory care, and the demands and priorities of individual patients and the community at large. PMID- 3098804 TI - Clinical uses of an enzyme-containing dentifrice. AB - Previous studies have shown that the inclusion of certain enzymes in mouthrinses and dentifrices will reduce plaque and gingivitis scores. The enzymes that are most effective clinically have, as their active ingredients, amyloglucosidase and glucose oxidase. These produce hydrogen peroxide from dietary fermentable carbohydrates which in turn converts thiocyanate to hypothiocyanite in the presence of salivary lactoperoxidase. The resultant hypothiocyanite acts as a bacterial inhibitor by interfering with cell metabolism; thus, there is a reduction in plaque accumulation and therefore in gingival inflammation. Pilot studies have compared over a short period the action of the trial dentifrice with enzymes and fluoride at 1100 ppm, using as controls the paste without enzymes but with fluoride and a commercial fluoride paste. There was an expected reduction in all scores with all products due to the mechanical removal of plaque, but a significantly greater reduction in gingivitis was noted in the paste with enzymes. This study is of longer duration with many more subjects. Baseline data include plaque and gingival indices and Periotron readings for crevicular fluid. The trial is of a double-blind non-crossover study design using a split-mouth technique. One side of the mouth is given a prophylaxis and the subject given one of the 3 test pastes to use. Readings were repeated every 2 weeks for 3 months. The results show a significant reduction in gingivitis scores in the enzyme containing dentifrice group. PMID- 3098805 TI - Cyclosporine serum concentrations soon after heart or heart-lung transplantation. AB - The accumulation of cyclosporine was evaluated in 11 patients following either heart or heart-lung transplantation. Blood samples were drawn frequently for the first few postoperative days, and the plasma was analyzed by both radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC). The levels determined by RIA were higher than those assessed by HPLC, and it is hypothesized that the difference is due to antibody reactive metabolites of cyclosporine, which are measured by the RIA procedure. We did not find any consistent trends in the accumulation of these metabolites. Analysis of early clinical data did not suggest any relationship between levels of cyclosporine or its metabolites and clinical outcome. PMID- 3098806 TI - Accumulation and washout kinetics of valproic acid and its active metabolites. AB - There is growing evidence that the metabolites of valproic acid (VPA) may be pharmacologically active and could contribute to both the therapeutic and toxic effects of the drug. The accumulation and washout kinetics of VPA and its oxidative metabolites were, therefore, examined in five healthy volunteers. Valproic acid (250-mg capsules) was administered bid for 15 days. Blood samples were obtained periodically during the 15 days of drug administration and for seven days following termination of treatment. Urine was also collected over the final dosing interval. Steady-state serum concentrations of VPA were achieved within three to four days of treatment. The accumulation of all metabolites in serum lagged behind that of the parent compound, with the mono-desaturated metabolites accumulating more slowly than the hydroxylated species. Furthermore, the apparent washout half-life of each metabolite was longer than the elimination half-life of VPA. In general, the unsaturated metabolites were eliminated more slowly than the hydroxylated metabolites. The serum and urinary metabolite profiles of VPA observed in the healthy volunteers were comparable with those reported for epileptic patients. The differences in the disposition kinetics of VPA and of its potentially active metabolites may explain the previously observed dissociation between the pharmacokinetics and pharmacodynamics of the drug in epileptic patients. PMID- 3098807 TI - Neurotoxic action of kainic acid in the isolated toad and goldfish retina: I. Description of effects. AB - The neurotoxic action of kainic acid (KA) was investigated by histological methods in the isolated retina of toads and goldfish. Particular attention was paid to the earliest and most sensitive response to KA in the outer plexiform layer (OPL). KA caused vacuolization of proximal and distal segments of horizontal cell dendrites in the OPL as well as perikaryal vacuolization and/or chromatin clumping in selected classes of neurons in the inner nuclear layer. Further, KA caused vacuolization and swelling in the inner plexiform layer. These effects were very similar in the retinae of goldfish and toad. The extent of vacuolization in the OPL was graded with KA concentration and with length of incubation. For 15-minute incubations, half-maximal vacuolization was found at 10 20 microM KA. At 25 microM KA, OPL vacuolization was evident within 1-2 minutes of application of KA. In goldfish, but not in toad, rod-connecting dendrites were less sensitive to KA than cone-connecting dendrites. PMID- 3098808 TI - Neurotoxic action of kainic acid in the isolated toad and goldfish retina: II. Mechanism of action. AB - The specificity and mechanism of the neurotoxic action of kainic acid (KA) was investigated by histological methods in the isolated retina of toads and goldfish. Particular attention was paid to the earliest and most sensitive response to KA in the outer plexiform layer (OPL). Of 21 compounds tested as potential mimics of KA neurotoxicity in the OPL, only the enantiomers of glutamate and aspartate mimicked KA, inducing a low-level neurotoxic effect at concentrations 5,000-10,000-fold higher than concentrations of KA giving comparable effects. Further, of 22 compounds tested as potential blockers of KA neurotoxicity in the OPL, only D-gamma-glutamylglycine, D,L-alpha-amino pimelic acid, sodium pentobarbital, D,L-alpha-amino adipic acid, L-glutamate, and L aspartate blocked KA neurotoxicity (IC50 values of 0.1, 0.3, 0.3, 2, 5, and 15 mM, respectively). In ionic substitution experiments, KA-induced vacuolization was found to require sodium and chloride ions but not calcium ions in the extracellular medium. These findings support the hypothesis that KA combines with specific receptors in the membrane of susceptible neurons in the retinal OPL, leading to prolonged opening of membrane channels permeable to sodium and potassium ions. An accompanying equilibrating chloride influx may result in intracellular ion excess, leading to osmotic swelling and vacuolization. The membrane receptors involved in mediating the action of KA in the OPL are likely to be a class of postsynaptic or extrasynaptic glutamate receptor. PMID- 3098809 TI - Day-night variations in blood and intracellular pH in a lizard, Dipsosaurus dorsalis. AB - Blood pH, PCO2 and PO2 of Dipsosaurus dorsalis were measured during the day and at night. Lizards at constant body temperature (25, 37 degrees C) and lizards experiencing diurnal changes in body temperature similar to those in nature were studied. In lizards at constant body temperatures, blood pH was about 0.1 unit less and blood PCO2 was 4-7 Torr higher at night compared to day. Similar patterns were seen in lizards on natural thermal cycles. Intracellular pH (pHi) of skeletal muscle, esophagus and liver was about 0.2 units lower at night than day but myocardial pHi was unchanged. Reduction in breathing frequency, and thus a relative hypercapnia from hypoventilation was consistent with the nocturnal acidification of the blood and intracellular compartments. Nocturnal acidification (CO2 retention) corresponds to periods of minimum metabolism. The possible impacts of diurnal shifts in hydrogen ion concentration on energy metabolism and metabolic regulation are discussed. PMID- 3098810 TI - "Don't forget to brush your teeth!" (Dr. Alfred Civilion Fones). PMID- 3098811 TI - New therapy for temporomandibular joint syndrome and associated pain problems. PMID- 3098812 TI - Influence of mastitis on growth of starter organisms used for the manufacture of fermented milks. AB - The effect of milk containing increased somatic cells on the starter organisms Streptococcus thermophilus, Lactobacillus bulgaricus and L. acidophilus was examined. Increased somatic cell count resulted in stimulation of Str. thermophilus owing to increased proteolysis, but inhibition of L. acidophilus as a consequence of increased phagocytic activity of the polymorphonuclear leucocytes PMID- 3098813 TI - Genetic polymorphism of bovine chymosin. PMID- 3098814 TI - Diabetic ketoacidosis-induced hyperkalemia. Prevalence and possible origin. AB - We report the biochemical data of 22 hospital admissions because of untreated diabetic ketoacidosis. Fifty percent of admitted patients showed an initial serum potassium between 4.6 and 6.0 mEq/l whereas severe hyperkalemia (value greater than 6.1 mEq/l) occurred in 32%. Initial potassium levels show a slight negative correlation with pH but a stronger correlation (p less than 0.001) was found between the initial serum potassium and glucose values. We suggest that hyperglycemia due to insulinopenia must be one of the factors in the pathogenesis of this hyperkalemia. PMID- 3098815 TI - Hypophosphatemia and acute respiratory failure in a diabetic patient. AB - A previously healthy 48-year-old male developed diabetic ketoacidosis and severe hypophosphatemia. Within a few hours, acute respiratory insufficiency developed with a marked discrepancy between the pulmonary pathology and the very poor oxygenation seen. We argue that this was due to the effect of hypophosphatemia on respiratory muscle- and heart function and P50, leading to impaired oxygen delivery. PMID- 3098816 TI - Comparative effects of intracoronary vasodilators on restoring coronary perfusion during flow-reducing coronary stenosis in the dog. AB - The effects of intracoronary injection of nitroglycerin, adenosine, nifedipine and prostacyclin on restoring coronary perfusion during flow-reducing partial coronary obstruction in anesthetized dogs were studied. Coronary obstruction was obtained by inflation of an intraluminal balloon to decrease coronary blood flow and rate of rise in left ventricular pressure (dP/dt) by approximately 30 to 40 and 10%, respectively. Nitroglycerin (0.01 to 10 micrograms/kg per min) increased coronary blood flow and distal coronary pressure and decreased stenosis resistance associated with improved left ventricular dP/dt depending on its dose. In contrast, adenosine (0.3 to 1.0 micrograms/kg per min) decreased coronary blood flow and distal coronary pressure and intensified stenosis resistance associated with depression of left ventricular dP/dt. Nifedipine and prostacyclin caused divergent effects on the coronary circulation related to each dose. Nifedipine (0.01 and 0.1 micrograms/kg per min) and prostacyclin (0.01 micrograms/kg per min) increased coronary blood flow and distal coronary pressure and reduced stenosis resistance. Nifedipine (1.0 micrograms/kg per min) and prostacyclin (0.3 micrograms/kg per min) did not increase coronary blood flow, but reduced distal coronary pressure and intensified stenosis resistance. Thus, the vasodilators produced different effects on restoration of coronary perfusion during pliable severe coronary stenosis. Nitroglycerin and lower doses of nifedipine and prostacyclin improved coronary perfusion due to selective or preferential dilation of large coronary arteries. Adenosine and higher doses of nifedipine and prostacyclin had deleterious effects on the coronary circulation due to potent arteriolar vasodilation. PMID- 3098818 TI - Recurrent premenstrual decline in serum lithium concentration: clinical correlates and treatment implications. PMID- 3098817 TI - Influence of left ventricular dysfunction on flecainide therapy. AB - Seventy-six patients with ventricular tachyarrhythmias (40 sustained and 36 nonsustained) were treated with oral flecainide. Radionuclide left ventricular ejection fraction was 30% or less in 33 patients and greater than 30% in 43 patients. Before flecainide, compensated heart failure was present in 23 patients (ejection fraction less than or equal to 30% in 15 and greater than 30% in 8). Flecainide mean dose was 150 mg twice daily and mean plasma concentration was 720 ng/ml. New or worsened congestive heart failure occurred in seven patients on flecainide therapy, all with an ejection fraction of less than 30%; six had a previous history of compensated heart failure and of these, three died. Ejection fraction was the only independent variable that significantly influenced efficacy and tolerance of flecainide. After 1 year of therapy, efficacy and tolerance was 58% (25 of 43) in patients with an ejection fraction greater than 30% and 12% (4 of 33) in patients with an ejection fraction of 30% or less (p less than 0.001). Thus, congestive heart failure can occur during flecainide therapy, particularly in patients with a previous history of congestive heart failure and ejection fraction of less than 30%, and may particularly limit therapy in these patients. Clinical efficacy and tolerance were significantly lower in patients with an ejection fraction of less than 30%. PMID- 3098819 TI - Provision of clinical nutrition services by diagnosis-related groups (DRGs) and major diagnostic categories (MDCs). PMID- 3098820 TI - Tube feeding utilization: a quality of care review. PMID- 3098821 TI - Nutritional status and dietary intake in institutionalized patients with Alzheimer's disease and multiinfarct dementia. AB - Nutritional status, dietary intake, weight change, and mortality were studied in a sample of severely demented, institutionalized patients. Dietary intake was registered during five days in two periods, five weeks apart. A weighing method was used. Nutritional status was assessed by anthropometric measurements (weight for height index, triceps skinfold thickness, arm muscle circumference) and determination of circulating proteins (albumin, transferrin, and prealbumin). Energy and/or protein malnutrition was found in 50% of the patients. The mean dietary intake was sufficient according to energy (2059 kcal/day), proteins, vitamins, and minerals. A comparison of patients with or without malnutrition showed no differences in dietary intake, diagnoses, age, length of hospital stay, or duration of illness. However, malnourished patients had had four times as many infectious periods treated by antibiotics as patients with no malnutrition. Thirty-nine of 44 patients lost weight during their hospital stay. There was no correlation between loss of weight, length of hospital stay, or duration of illness. PMID- 3098823 TI - [Female karyotype and male phenotype: XX men. Apropos of 2 cases]. AB - Males with a female karyotype are of special interest because they bear potential information on male determining factors leading to a masculine development in spite of a normal female chromosome constitution. We present 2 XX males, the clinical features correspond closely to many of those described in De La Chapelle's series of 46,XX males: reduced body height, infertility with small testicles, marked seminiferous tubular atrophy and azoospermia, slightly decreased testosterone level in serum and increased FSH and LH levels. Four main classes of theories concerning the etiology of XX males are presented, while mosaicism appears very unlikely in most cases, autosomal gene mutation, deletion or inactivation of X-chromosomal genes, X-Y interchange remain possible. The etiology of XX maleness may well be heterogeneous. PMID- 3098822 TI - Increased serum thyroglobulin concentrations and impaired thyrotropin response to thyrotropin-releasing hormone in euthyroid subjects with endemic goiter in Sicily: their relation to goiter size and nodularity. AB - Serum thyroglobulin (Tg), T4, T3, FT4, FT3, TSH concentrations and TSH response to iv TRH (delta TSH) were measured in 56 consecutive patients with (multi) nodular goiter from a severely iodine-deficient endemic goiter area in Northeastern Sicily and in 11 non goitrous euthyroid individuals living in the same area. Serum Tg concentrations were sharply increased in goitrous subjects (453 +/- 476 ng/ml) and related to thyroid size and the presence of nodules (chi 2 = 43.5, p less than 0.0005). Serum TSH levels measured in goitrous patients (2.1 +/- 0.9 microU/ml) were significantly lower than those measured in nongoitrous iodine deficient subjects (3.1 +/- 0.9 microU/ml, p less than 0.001) and decreased with increasing goiter size and nodularity (chi 2 = 27.3, p less than 0.05). A similar pattern was shown by the analysis of the delta TSH (chi 2 = 43.1, p less than 0.0005). These results suggest that at least a part of the largest and multinodular goiters become autonomously functioning with duration and growing in size. In 13 goitrous patients with absent or impaired response to TRH, a significant direct relation was apparent between log-Tg and goiter size and nodularity (r = 0.64) with an inverse relationship between serum FT3 and delta TSH (r = 0.73). A computed program analysis based on the combination of different independent variables (x) including age, thyroid size and nodularity, serum TSH, log-Tg and FT3, indicated the existence of a significant negative relationship between these variables and the TSH response to TRH (r = 0.75, p = 0).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098824 TI - [Sheehan's syndrome followed by spontaneous pregnancy. Apropos of 2 cases]. AB - There are few reports of spontaneous pregnancies in patients with Sheehan's syndrome. We describe two cases which exhibited adrenal and thyroid insufficiency but not amenorrhea, return of the menstrual periods being at the expected time after delivery. Endocrinologic studies confirmed thyrotropin and corticotropin insufficiency. Clinical evidence of preserved gonadotropin secretion was supported by the response of LH and FSH to acute administration of synthetic LHRH and by the fact that thyroid and corticoid hormonal replacement resulted in a spontaneous pregnancy with successful outcome. PMID- 3098825 TI - [Stimulation of ovulation by pure FSH for in vitro fertilization. Study of the route of administration]. AB - Pulsatile injection of FSH to stimulate ovulation for in vitro fertilization was undertaken in order to compare the intramuscular route with the pulsatile subcutaneous route in two groups of 6 patients each selected at random. The patients were selected in such a way as to reduce as far as possible the parameters that would make it difficult to interpret the results. Both from the point of view of the numbers of patients who responded to stimulation of ovulation as well as the numbers of pregnancies that were obtained, the intramuscular route seems to be preferable. PMID- 3098826 TI - Genioglossus and alae nasi activity in fetal sheep. AB - The functional development of two upper airway dilating muscles, the alae nasi and the genioglossus, has been studied in fetal sheep in utero from 112-140 days gestation. Before electrocortical differentiation phasic activity was present in both muscles for long periods, mostly when breathing movements were present. After 120 days gestation phasic genioglossal and alae nasi activity occurred only during periods of low voltage electrocortical activity. During high voltage episodes there was no phasic activity and tonic activity was not sustained. Although present during periods of breathing movements genioglossus activity was rarely synchronous with the diaphragm. The alae nasi showed both respiratory and non-respiratory related activity. Hypoxia abolished both alae nasi and genioglossus activity but whereas alae nasi rapidly developed an inspiratory rhythm during 5% CO2 administration this was not the case with the genioglossus and inspiratory activity was not always seen in the genioglossus even during 10% CO2 administration. It is concluded that there are fundamental differences between the control of genioglossus and alae nasi activity in the fetal sheep. The alae nasi behaves as an inspiratory muscle responding to hypoxia and hypercapnia as would be expected but the genioglossus shows no inspiratory activity during normal unstimulated fetal breathing. Thus the neural mechanisms for activation of inspiratory activity appear to be present late in gestation. However it is possible for the genioglossus to develop an inspiratory rhythm under conditions of much increased respiratory drive. PMID- 3098827 TI - Case mix reimbursement for nursing homes. AB - Nursing home care is growing in importance as the population ages and as Medicare's prospective payment system encourages earlier discharges from acute care settings to nursing homes. Nursing home reimbursement policy is primarily a Medicaid issue, since Medicaid pays for about half the nation's nursing home care. The research reviewed in this article suggests a strong association between case mix and cost, and a weaker but still positive association between quality and cost. The research also implies that traditional nursing home reimbursement methodologies may impede access and may lower quality for Medicaid (and Medicare) recipients. To offset these problems, several states have recently begun to incorporate case mix directly into the reimbursement process. These systems deserve careful policy consideration. PMID- 3098828 TI - Hard choices: targeting long-term care to the "at risk" aged. AB - Recent expansion of Medicaid coverage to home- and community-based long-term care moves that payment program away from its traditional institutional bias. But tension over the appropriate role of home care and fears of budget-busting have caused the current administration to set goals for the states that may be impossible to achieve. PMID- 3098829 TI - Optimization of culture conditions for the maintenance of Onchocerca gutturosa adult worms in vitro. AB - A series of experiments examined the effects of various media, serum supplements, gas phases and the incorporation of mammalian cell feeder layers on the survival of Onchocerca gutturosa adult worms in vitro. The survival of male worms was poor in all media tested that were not supplemented with inactivated foetal calf serum (IFCS), with improved but variable survival in media supplemented with 10-30% IFCS. Using a cell-free system in an atmosphere of 5% CO2 in air, good results were obtained in medium NCTC 135 + 10% IFCS (median survival time 39 days, range 25-41). Marginally better survival was obtained with the same medium in an atmosphere of 95% N2/5% CO2 (median 45 days, range 25-56) and with a 1:1 mixture of media NCTC 135 and IMDM + 10% IFCS (median 38 days, range 38-51). Survival was enhanced in culture systems which incorporated bovine kidney (MDBK) cells, bovine trachea (EBTR) cells and monkey kidney (LLCMK2) cells. Exceptionally long survival was obtained using medium MEM + 10% IFCS + LLCMK2 cells under a gas phase of 5% CO2 in air, in which male worms survived from approximately 6 to over 7 months. Under similar conditions, female worms were also maintained for periods of up to 6 months and 5 out of 18 specimens released microfilariae into the culture system. The long-term culture described in this study will be useful for basic biochemical, chemotherapeutic and immunological studies in vitro. PMID- 3098830 TI - Electron microscopic cytochemical localization of adenylate cyclase in amphibian urinary bladder epithelium: effects of antidiuretic hormone. AB - A cytochemical technique for electron microscopic localization of adenylate cyclase was used to identify this enzyme in quiescent and hormone-stimulated toad urinary bladder epithelium. In the absence of vasopressin (antidiuretic hormone), adenylate cyclase was detected along the outer surface of the basolateral plasma membranes of granular cells, mitochondria-rich cells, and basal cells, the major cell types comprising the hormone-sensitive urinary epithelium. In the presence of antidiuretic hormone, the basolateral precipitates were markedly increased. The latter was true for both tissues incubated in the presence of an osmotic gradient and those stimulated in the absence of such a gradient. A significant mucosal reaction was never seen. Such data indicate that the hormone receptors for vasopressin are located along the basolateral membranes of all epithelial cells comprising the mucosal hormone-sensitive epithelium. All cells of the epithelium also demonstrate a vasopressin-sensitive adenylate cyclase. We discuss possible mechanisms that attempt to integrate the cytochemical data into an overall scheme for the physiological action of this hormone on amphibian urinary bladder. PMID- 3098832 TI - Improved preservation of glycogen in unfixed cyanobacteria embedded at -82 degrees C in nanoplast. AB - A technique is presented for embedding unfixed cells at -82 degrees C in Nanoplast, a water-soluble melamine resin. By use of this procedure, improved ultrastructural preservation is demonstrated in cyanobacteria. Sections treated in this way are suitable for histochemical techniques such as Thiery's silver staining method for glycogen. PMID- 3098831 TI - Chromogranin in bronchopulmonary neuroendocrine cells. Immunocytochemical detection in human, monkey, and pig respiratory mucosa. AB - Immunoreactive chromogranin A was demonstrated by immunocytochemistry in the cytoplasm of neuroendocrine cells (NEC) and neuroepithelial bodies (NEB) in human, monkey, and pig respiratory mucosa. Three different antisera (one monoclonal and one polyclonal to human chromogranin A, and one polyclonal to bovine chromogranin A) were applied in this study. Chromogranin immunopositivity varied in extent and intensity according to the antiserum applied and the tissue investigated. The monoclonal antibody revealed the strongest immunoreaction. Good correlation between chromogranin immunoreactivity and Grimelius silver staining was observed by comparing adjacent sections, although more cells seemed to reveal chromogranin immunoreactivity than argyrophylia. Chromogranin appears to be a useful histological marker for APUD cells in the respiratory mucosa of several species. PMID- 3098833 TI - Detection of plasma cell immunoglobulins in tissue sections optimally fixed for ultrastructural immunocytochemistry. AB - We describe the ultrastructural localization of plasma cell immunoglobulins in vibratome sections of popliteal lymph nodes. Fixation with glutaraldehyde paraformaldehyde gave better tissue and antigen preservation than paraformaldehyde or periodic acid lysine-paraformaldehyde; biotinylated Fab fragments of sheep anti-mouse IgG-streptavidin-biotinylated horseradish peroxidase (HRP) or Fab-HRP conjugates gave similar results. With both immunoreagents, excellent tissue preservation and antigen detection was observed in the first layer of cells sectioned with the vibratome. Conjugates of anti mouse IgG with HRP did not show any staining. Peroxidase stain was observed in the nuclear envelope, cisternae of the rough endoplasmic reticulum, and the Golgi apparatus complex. In the Golgi apparatus, staining was seen consistently in cisternae of the cis face and in adjacent vesicles; the trans cisternae showed weak or no stain, and adjacent vesicles, "coated" vesicles, and granules were not stained. This study shows that high quality of tissue preservation and antigen detection, by both light and ultrastructural immunocytochemistry, is feasible in tissue fixed with glutaraldehyde-paraformaldehyde followed by vibratome sectioning and immunostaining with Fab-biotin-streptavidin-biotin-HRP, or Fab HRP. PMID- 3098834 TI - Endogenous peroxidase activity in human cutaneous and adenoidal mast cells. AB - We have studied peroxidase activity in human cutaneous and adenoidal mast cells using different methods, in order to determine the optimal technical conditions for its demonstration. In 1.25% glutaraldehyde-fixed cells, no peroxidase activity was seen. On the contrary, in tannic acid-aldehyde-fixed cells or in unfixed cells peroxidase activity was revealed independently of the DAB concentration or the incubation time in DAB medium. The reaction product was localized in perinuclear cisternae and endoplasmic reticulum. Granules were always unreactive with all techniques employed. Golgi apparatus was generally negative and only occasional cells exhibited one or two positive peripheral cisternae. This activity appears sensitive to fixation by glutaraldehyde and is inhibited by 3-amino-1,2,4-triazole (AMT) and by lack of H2O2 or DAB in the incubation medium, but not by potassium cyanide, sodium azide, or sodium pyruvate, at the concentrations used. The peroxidase activity described in this report is an endogenous peroxidase and is not related to uptake of exogenous peroxidase by mast cells. It can therefore be considered as an ultracytochemical marker of human mast cells. PMID- 3098835 TI - Histomorphometric identification of carbonic anhydrase in fetal rat bone embedded in glycolmethacrylate. AB - Carbonic anhydrase was identified in bone-resorbing cells present in sections of fetal rat femur embedded in glycolmethacrylate. Using a slight modification of the Hansson's histochemical method, we demonstrated that most chondroclasts (91.8 95.4%) and osteoclasts (95.1-96.3%) display a positive histochemical reaction for carbonic anhydrase. This staining was consistently inhibited in the presence of very low concentrations (10(-6), 10(-7) M) of the specific inhibitor acetazolamide. The number of chondroclasts reacting for carbonic anhydrase was identical to the number of acid phosphatase-stained chondroclasts determined on adjacent sections. A large majority of osteoclasts (96.3%) stained for carbonic anhydrase and for acid phosphatase (97.2%), with more osteoclasts reacting for the latter enzyme than the former (76.8 +/- 8.5 (SD) vs 85.3 +/- 9.2 cells/mm2 of endosteal bone; p less than 0.01). The observation that acetazolamide at a concentration as low as 10(-7) M inhibited Hansson's reaction, together with our histomorphometric results, validates the use of histochemical staining for carbonic anhydrase to evaluate activity of bone-resorbing cells identified in plastic-embedded fetal bone tissue. PMID- 3098836 TI - Enzyme immunoassay using BCG in serodiagnosis of pulmonary tuberculosis. AB - Amounts of Mycobacterium tuberculosis antibodies were determined in sera from patients with either active or inactive tuberculosis and in healthy subjects by an immunoenzymatic assay in which whole BCG cells attached covalently to polystyrene disks were used as antigen. Statistically significant differences (P less than 0.005) were found both between the active and inactive tuberculosis groups and between the active group and healthy controls. No significant differences were found between the inactive group and controls. Since this procedure is efficient (91%) and can be used in areas which lack laboratory equipment, it appears promising for individual serodiagnosis and for epidemiological surveys. PMID- 3098837 TI - Platelets in human essential hypertension: in vitro hyperreactivity to thrombin. AB - Platelet reactivity of normotensive and essential hypertensive subjects was examined in vitro. We determined the release of [3H]-serotonin induced by thrombin from washed platelets in the presence of calcium (10(-3) mol/l) or with EGTA (calcium free medium). The release was significantly higher from platelets of hypertensive subjects when compared with those of normotensive subjects. This difference was only found in the presence of external calcium. The present data suggest an intrinsic functional hyperreactivity of platelets from essential hypertensive patients, which may be linked to an alteration in calcium (Ca2+) handling. PMID- 3098838 TI - Thymocyte binding to human thymic epithelial cells is inhibited by monoclonal antibodies to CD-2 and LFA-3 antigens. AB - With the use of cultured human thymic epithelial (TE) cells, we have previously shown that thymocytes bind to TE cells in suspension in a rosette-forming assay. To identify cell surface molecules involved in human TE-thymocyte rosette formation, we assayed a large panel of monoclonal antibodies for their ability to inhibit rosette formation. We found anti-CD-2 (LFA-2, T11), and anti-LFA-3 antibodies all inhibited binding of TE cells to thymocytes. By using indirect immunofluorescence assays, we determined that cultured TE cells were 90% LFA-3 positive and CD-2 negative, whereas thymocytes were 10% LFA-3 positive and 98% CD 2 positive. Pretreatment of TE cells with anti-LFA-3 but not anti-LFA-2 inhibited TE-thymocyte binding. In contrast, pretreatment of thymocytes with anti-CD-2 but not anti-LFA-3 antibodies inhibited TE-thymocyte binding. Thus TE cell-thymocyte binding is blocked by antibodies to the CD-2 (T11) antigen on thymocytes and by an antibody to the LFA-3 antigen on TE cells. Because the CD-2 antigen has been implicated in T cell activation, these data suggest that a natural ligand for T cell activation via the CD-2 molecule is present on human thymic epithelial cells. PMID- 3098839 TI - Expression of asialo GM1 on a subset of adult murine thymocytes: histological localization and demonstration that the asialo GM1-positive subset contains both the functionally mature and the proliferating thymocyte subpopulations. AB - A small population (10 to 14%) of adult murine thymocytes expresses the glycolipid asialo GM1 (aGM1). Flow cytometric analysis of the aGM1+ cells present in thymus demonstrates the expression of a mature or medullary phenotype by 50% of the aGM1+ cells. Analysis of cytotoxic T lymphocyte precursor activity, proliferative capacity, and IL 2 production displayed by aGM1+ and aGM1- thymocyte fractions isolated by cell sorting indicates that these functional compartments of the thymus are contained within the aGM1+ subset. The aGM1+ population also contains virtually all mitotically active thymocytes, as measured by incorporation of bromodeoxyuridine. The immature IL 2 receptor-bearing thymoblasts are also included in the aGM1+ population. Immunohistochemical labeling of thymic tissue sections reveals that the majority of aGM1+ cells are located in the medulla. Clusters of aGM1+ cells are found scattered throughout the cortical and subcapsular areas. The aGM1+ population therefore contains the functionally mature thymocytes as well as some immature thymocytes, particularly those that are mitotically active. It is suggested that the aGM1+ subset of thymocytes represents those cells that are mature or actively maturing. This hypothesis is discussed in the context of current concepts of intrathymic T cell differentiation pathways. PMID- 3098840 TI - Dissection of defective antigen presentation by interferon-gamma-treated fibroblasts. AB - The capacity of interferon-gamma (IFN-gamma)-treated HLA-DR expressing human dermal fibroblasts (FB) to function as antigen-presenting cells (APC) was examined. FB were cultured with 250 U/ml IFN-gamma for 4 days to induce HLA-DR expression. Peripheral blood monocytes (M phi), FB, or IFN-gamma-treated FB from the same donor were then cultured overnight with or without the recall antigen streptokinase streptodornase (SKSD), and their capacity to stimulate autologous T4 cell DNA synthesis was examined. SKSD-bearing M phi stimulated T4 cell proliferation, whereas antigen-bearing HLA-DR (+) FB did not. Even after fixation with paraformaldehyde to eliminate metabolic activity, SKSD-bearing M phi, but not FB, were able to function as APC. However, when HLA-DR (-) endothelial cell (EC) or autologous or HLA-D-mismatched M phi were added to the cultures, antigen pulsed IFN-gamma-treated FB and M phi were comparably effective stimulators of autologous T4 cell DNA synthesis. Antigen recognition by the T4 cell was restricted by the class II major histocompatibility complex (MHC)-encoded gene products expressed by the IFN-gamma-treated FB and was unrelated to the class I or II MHC-encoded gene products expressed by the additional cell type. EC promoted T4 cell DNA synthesis induced by antigen-bearing IFN-gamma-treated FB was inhibited by 60.3, a monoclonal antibody directed at an epitope common to LFA 1, CR3, and the p150,95 molecule. Inhibition caused by 60.3 was completely reversed by the addition of IL 2 to the cultures. Antigen presentation by IFN gamma-treated FB was also enhanced somewhat by IL 1, IL 2, or monoclonal antibody directed at Tp44 (9.3). However, each of these additions alone promoted T cell proliferation less effectively than EC and resulted in responses that were smaller than those triggered by antigen-bearing M phi. The data suggest that IFN gamma-treated FB take up and process antigen effectively, but lack an accessory cell property necessary for antigen-induced T4 cell IL 2 production and proliferation. PMID- 3098841 TI - The effects of phorbol ester on alloantigen presentation. AB - B cells and Ia+ thyroid cells fail to stimulate alloreactive T cells in a primary mixed leukocyte reaction (MLR) and fail to activate some allo-class II (I-A) reactive T cell hybridomas. We now demonstrate that B cells can specifically stimulate a primary MLR in combination with the phorbol ester, PMA, but not with interleukin 1 (IL 1) or calcium ionophore. The primary MLR induced with B cells plus PMA can be blocked by either monoclonal anti-I-A or anti-L3T4 antibodies. In contrast, thyroid cells that can be induced to express Ia antigens after incubation with interferon-gamma fail to stimulate a primary MLR even in the presence of PMA or IL 1. We confirmed these observations by using the alloreactive T cell hybridoma, HTB-9.3, which does not react to stimulator B cells. In the presence of PMA, however, this I-Ab-specific hybridoma line was able to respond to relevant but not to control stimulator B cells. Furthermore, the response of HTB-9.3 to B cells plus PMA was also blocked by anti-I-A or anti L3T4 antibody. In contrast to B cells, Ia+ thyroid cells could not activate HTB 9.3 even in the presence of PMA or IL 1. The data indicate that for primary class II restricted allo-responses, B cells provide signals that can be complemented with the phorbol ester PMA, whereas Ia+ thyroid cells do not, suggesting the existence of additional requirements for T cell activation. PMID- 3098842 TI - Glucocorticoid receptors and corticosensitivity of human thymocytes at discrete stages of intrathymic differentiation. AB - Human thymus is composed of several discrete compartments. Stage III thymocytes, located mainly in the medulla, stain brightly with anti-T3 monoclonal antibody; stage II thymocytes, located in the cortex, are T3- but react with T6 antibodies. The earliest identifiable intrathymic cell (stage I) expresses the sheep erythrocyte glycoprotein T11 but not T6 or T3 antigens. Within the thymus a phenotypically heterogeneous pool of proliferating lymphoblasts is present. This capacity to proliferate without in vitro activation is mainly attributable to thymocytes unable to respond to mitogens and expressing the cortical T6 marker. Both T3+ and T3-T6- cells respond to mitogen. However, in order to exhibit maximal proliferative responses, T3+ but not T3-T6- thymocytes require the addition of exogenous IL 2. Thymocyte subsets at distinct stages of intrathymic differentiation were then analyzed for glucocorticoid (GC) receptor content by using a whole cell assay with 3H-triamcinolone acetonide as tracer. The least mature T3-T6- thymocyte subset contained the highest levels of GC receptors . T3+ thymocytes exhibited a receptor content higher than that found in T6+ cells and similar to that reported for peripheral blood lymphocytes. Apart from the number, the GC receptor sites in all thymocyte subsets were similar in their affinities, kinetic characteristics, specificity for steroids, and ability to undergo translocation from cytoplasm to nucleus, and they behave in all these respects like binding sites of GC receptors in lymphoid and other cells. Independently of both phenotype and GC receptor content, all in vivo activated thymocytes (i.e., spontaneously proliferating cells) were similarly sensitive to the steroid inhibitory action in vitro. Both in the presence and in the absence of exogenous IL 1 or IL 2, the PHA-induced mitogenesis of T3-T6- cells was less inhibited by GC than that of T3+ thymocytes. Exogenous IL 1 and IL 2 were equally effective in removing, although not completely, the GC inhibition on T3-T6- proliferative responses to PHA. Relative to T3+ cell mitogenesis, only exogenous IL 2 was able to antagonize the steroid inhibitory action. The capacity observed in vitro of GC to differentially affect the proliferative potential or the cell viability of thymocytes belonging to functionally distinct subsets suggests that these hormones could regulate the intrathymic maturative pathways. Finally, although at present the physiologic relevance of the highest expression of GC receptors in intrathymic precursor cells remains unclear, the receptor density may be considered a marker of differentiation for the T lymphoid lineage. PMID- 3098843 TI - Abrogation of bone marrow allograft resistance in mice by increased total body irradiation correlates with eradication of host clonable T cells and alloreactive cytotoxic precursors. AB - Host-vs-graft activity presents a major obstacle for transplantation of T cell depleted bone marrow in HLA-mismatched patients. In a primate model, conditioned exactly like leukemia patients, it was shown that residual host clonable T cells, as well as alloreactive cytotoxic precursors, were present in peripheral blood and spleen after completion of cytoreduction. We have now extended this study in a mouse model for allogeneic bone marrow transplantation. C3H/HeJ mice were treated by 9 Gy total body irradiation (TBI), and 24 hr later their spleen cells were cultured in the presence of T cell growth factor and phytohemagglutinin according to the limit dilution procedure. After 7 days of culture the average frequency of clonable cells was 2.5 X 10(-3) compared with 37 X 10(-3) in the spleens of normal mice. The T cell derivation of the growing cells was ascertained by complement-mediated cytotoxicity with anti-Thy-1 as well as with anti-Lyt-2 and anti-Ly-3T4. In parallel, we found that the initial engraftment rate of bone marrow allograft in mice given 9 Gy TBI was lower than that found in recipients of syngeneic marrow. The initial engraftment rate was measured by the number of colony-forming units in the spleen and by splenic uptake of 125IUdR. A slight increase in TBI from 9 Gy to 11 Gy markedly reduced the difference in the number of spleen colony-forming units or the IUdR uptake between recipients of allogeneic and syngeneic bone marrow. This increase in TBI also coincided with eradication of detectable clonable T cells. Moreover, in mice transplanted with T cell-depleted bone marrow after 9 Gy TBI, we also demonstrate that cytotoxicity against donor-type target cells is present in the spleen 10 to 14 days posttransplantation, whereas in mice treated by 11 Gy TBI such alloreactivity could not be detected. These results suggest that resistance to T cell-depleted allogeneic bone marrow in irradiated mice closely correlates with the frequencies of residual host clonable T cells detectable by conventional immunologic assays. PMID- 3098844 TI - In vivo expression and regulation of murine IL 2 receptors after antigen sensitization. AB - We have studied the in vivo regulation and expression of the murine IL 2 receptor after antigen sensitization. High and low affinity receptor expression has been studied by flow cytometry analysis and radiolabeled IL 2 binding. Both anti-IL 2 receptor antibody and unlabeled IL 2 inhibited the radiolabeled IL 2 binding. The kinetics of expression of the IL 2 receptor closely correspond to the proliferative response, as assessed by IUdR radioisotope uptake. The expression of IL 2 receptors correlated with the proliferative response profile of the murine strains surveyed during a study of responses to picryl chloride. Neither immune compromised 4-mo-old MRL/lpr mice nor athymic nude mice generated significant antigen-specific proliferative responses or IL 2 receptor expression after antigen sensitization. Mice rendered specifically unresponsive to antigen displayed reduced proliferative responses to the tolerizing antigen, as well as reduced numbers of IL 2 receptor-positive cells. Finally, the treatment of mice with immunosuppressive drugs reduced both the proliferative responses as well as the number of IL 2 receptor-positive cells. However, at the cellular level, the drugs produced different effects on IL 2 receptor expression. PMID- 3098845 TI - Interleukin 2 regulates the expression of IL 2 receptors on interleukin 3 dependent bone marrow-derived cell lines. AB - Two IL 3-dependent bone marrow-derived cell lines, FD.C/1 and 32Dcl-23, have been converted to IL 2-dependent growth states. In the case of the FD.C/1 cell line, a small subpopulation of cells converted to IL 2 growth dependence, whereas for the 32Dcl-23 cell line, most cells readily converted to IL 2 growth dependence. IL 2 receptor expression was followed in FD.C/1 and 32Dcl-23 cells in both IL 3-and IL 2-dependent growth states, by analyzing transcription of IL 2 receptor-specific RNA and the subsequent expression of cell surface receptors. The exposure of IL 3 dependent cell lines to IL 2 resulted in rapid increases in the transcription of IL 2 receptor-specific RNA and receptor expression. The addition of IL 3 to IL 2 dependent cell lines did not alter the expression of the IL 2 receptor. When IL 2 was removed from the culture medium of these cells, the presence of IL 3 maintained a higher level of IL 2 receptor expression than was observed in the absence of lymphokines. PMID- 3098846 TI - In vivo and in vitro activation of alveolar macrophages by recombinant interferon gamma. AB - In vivo administration of recombinant interferon-gamma (rIFN-gamma) was previously shown to result in activation of the microbicidal activities of peritoneal macrophages (PM phi). Because macrophages at different anatomical sites vary in their functional capacities, we considered it of interest to determine whether administration of murine rIFN-gamma, either in vitro or in vivo, can enhance the microbicidal activity of resident alveolar macrophages (AM phi) and to compare the effects of rIFN-gamma on AM phi and PM phi. After incubation in vitro with rIFN-gamma, the antimicrobial activities of both murine AM phi and PM phi were enhanced, as assessed by their ability to inhibit replication of the intracellular parasite, Toxoplasma gondii. This effect was dose dependent for AM phi over a range of 0.1 to 1 U/ml and for PM phi over a range of 0.5 to 1000 U/ml. In this assay, the minimum dosage required for in vitro activation of AM phi was one-half that required for activation of PM phi, suggesting a greater sensitivity of AM phi to the in vitro activity of rIFN gamma. Macrophages from both anatomical sites were also activated when rIFN-gamma was administered in vivo. This effect was dose dependent over a range of 10(3) to 10(5) U/mouse. Freshly harvested AM phi and PM phi from mice injected 24 hr earlier with 10(4) U rIFN-gamma by either the i.v. or i.p. routes markedly inhibited intracellular multiplication of Toxoplasma. In contrast, AM phi and PM phi from control mice permitted fourfold to ninefold increases in numbers of intracellular Toxoplasma. The anti-toxoplasma activity of AM phi and PM phi gradually diminished over a period of 3 days when assayed at successive 24 hr periods after a single i.v. injection of rIFN-gamma. At 3 days after injection, a substantial loss of anti-toxoplasma activity was observed with PM phi as compared with controls; residual anti-toxoplasma activity was still demonstrable in AM phi at 3 days. These results demonstrate that in vitro as well as in vivo treatment with rIFN-gamma confers on AM phi an enhanced antimicrobial activity. These findings provide a rationale for evaluating rIFN-gamma in the treatment of pulmonary infections, especially those due to opportunistic pathogens against which AM phi play a major role in host defense. PMID- 3098848 TI - Role of membrane potential in the response of human T lymphocytes to phytohemagglutinin. AB - We have analyzed the role of membrane potential on T cell activation and cell proliferation. Depolarization of T lymphocytes, by increasing the extracellular concentration of K+ during a 1-hr exposure to PHA, results in a marked inhibition of cell proliferation. In parallel, depolarization of T cells prevented the normal increase in [Ca2+]i seen after PHA binding. In depolarized cells, PHA failed to induce IL 2 secretion, but, in contrast, IL 2 receptor expression was triggered normally and the cells were subsequently responsive to exogenous IL 2. Increasing [Ca2+]i in depolarized cells with the ionophore ionomycin, or bypassing the requirement for an increase in [Ca2+]i with TPA, restored the PHA induced proliferative response in depolarized cells. These data confirm that a membrane potential-sensitive step, namely, Ca2+ influx and the resulting change in [Ca2+]i, is triggered by PHA. The inhibitory effects of depolarization are mediated through the impairment of IL 2 secretion, but not IL 2 receptor expression. T cell proliferation can therefore be regulated by altering membrane potential, which in turn modulates the extent of the change in [Ca2+]i. This study suggests a role for transmembrane potential in the regulation of the T cell proliferative response. PMID- 3098847 TI - Human monocyte or recombinant interleukin 1's are specific for the secretion of a metalloproteinase from chondrocytes. AB - Macrophage products induce production of proteases that contribute to cartilage degradation in various joint diseases. In these studies we stimulated rabbit chondrocytes with various cytokines in vitro in order to determine which were responsible for changes in the release of prostaglandin, plasminogen activator, and a metalloproteinase. The metalloproteinase assayed in these studies is a latent enzyme whose activity can rapidly be measured with fluorogenic casein. Conditioned media from stimulated human peripheral blood mononuclear cells; purified human monocyte IL 1, pI 7,6, and 5; and recombinant human IL 1, beta or alpha forms, all changed the secretory pattern of rabbit articular chondrocytes in a similar manner: production and secretion of a latent metalloproteinase(s) and prostaglandin E were stimulated in a concentration-dependent fashion, whereas the activity of plasminogen activator was strongly reduced. Antibodies against human monocyte IL 1 blocked the active principle in various mononuclear cell conditioned media, suggesting that uncharacterized factors present in these supernatants do not affect the metalloproteinase response. When added to confluent chondrocytes, phorbol myristate acetate, concanavalin A, IL 2, lipopolysaccharide, indomethacin, and prostaglandin E2, which interfere with lymphocyte proliferation assays for IL 1, failed to influence chondrocyte metalloproteinase secretion. Recombinant human IFN-alpha or IFN-gamma in the presence or absence of IL 1 had no effect on rabbit chondrocytes, whereas recombinant human tumor necrosis factor decreased plasminogen activator but had no effect on prostaglandin or metalloproteinase production. These results support the concept that IL 1 specifically induces chondrocytes to produce metalloproteinases, and hence may play an important role in destructive joint diseases. PMID- 3098849 TI - Arachidonic acid metabolism in guinea pig Langerhans cells: studies on cyclooxygenase and lipoxygenase pathways. AB - Epidermal Langerhans cells are macrophage-like la+ leukocytes that are critically involved in cutaneous immune reactions. Because macrophages exert their immunoregulatory activity in part by generation of oxygenated arachidonic acid metabolites, we systematically studied arachidonic acid transformations by purified guinea pig Langerhans cells and compared them with mixed epidermal cells and Langerhans cell-depleted keratinocytes. Products formed from arachidonic acid by cell homogenates were measured after thin-layer or reverse-phase high-pressure liquid chromatographic separation. In addition, leukotriene B4 and C4 formation was assessed in supernatants of Ca ionophore A23187-challenged intact cells by radioimmunoassay. Mixed epidermal cells converted arachidonic acid predominantly via cyclooxygenase and 12-lipoxygenase pathways. The main products were prostaglandin D2 (PGD2) and 12-hydroxyeicosatetraenoic acid (12-Hete), although significant amounts of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha were formed as well. PGD2 synthesis was dependent on the presence of reduced glutathione. The product spectrum formed by Langerhans cell-depleted keratinocytes was virtually indistinguishable from mixed epidermal cells. In contrast, Langerhans cells showed a markedly different metabolism of arachidonic acid. They exhibited an exceedingly high PGD2-generating capacity, whereas only minor amounts of 12-HETE and very low amounts of other prostaglandins were synthesized. The PGD2/12-HETE ratio was 1.22 for mixed epidermal cells and 4.37 for Langerhans cells. Leukotriene production from exogenous or endogenous arachidonic acid could not be demonstrated by either radioenzymatic or radioimmunologic detection methods. We conclude that guinea pig Langerhans cells transform arachidonic acid predominantly to PGD2, which might mediate significant immunoregulatory, inflammatory, and antitumoral activity in the skin. PMID- 3098850 TI - Changes in gene expression induced by a phorbol diester: expression of IL 2 receptor, T3, and T cell antigen receptor. AB - Phorbol esters cause an apparent differentiation of human T leukemic cell lines. It was shown previously that TPA induces the expression of the interleukin 2 (IL 2) receptor and the T3 complex on some T cell lines, including CCRF-CEM. We demonstrate that expression of the IL 2 receptor correlated with an induction of the 3.5 and 1.5 kb IL 2 receptor mRNA. In addition, the TPA-induced expression of the T3 polypeptides was found to be accompanied by induction of a putative T cell antigen receptor heterodimer on CEM cells. This was demonstrated by the co precipitation of the T cell receptor with T3 from digitonin-solubilized cells. The cells expressed high levels of T3 delta- and T cell receptor beta-chain mRNA in the absence of TPA. The effect of TPA was to cause a rapid accumulation of T cell receptor alpha-chain mRNA. This suggested that the alpha-chain gene was rearranged before TPA induction and that expression of the T cell receptor/T3 complex on the cell surface was regulated by the level of alpha-chain expression. It was also shown that cloned sublines of CEM cells which expressed different T cell antigen phenotypes differed in their response to TPA. PMID- 3098851 TI - Tumor necrosis factor is an important mediator of tumor cell killing by human monocytes. AB - The mechanism of human peripheral blood monocyte-mediated cytotoxicity for tumor cells was investigated, using the A673 human rhabdomyosarcoma and HT-29 human colon adenocarcinoma lines as target cells. A673 cells were shown to be susceptible to the cytotoxic action of purified recombinant human tumor necrosis factor (TNF). A673 cells were also highly sensitive to the cytotoxic action of peripheral blood monocytes. Clones of A673 cells sensitive and resistant to TNF were isolated and characterized for their sensitivity to monocyte killing. A good correlation was found between the sensitivity of these clones to the cytotoxicity of TNF and their susceptibility to killing by monocytes. A TNF-specific neutralizing monoclonal antibody (MAb) reduced monocyte killing of parental A673 cells and of a TNF-sensitive clone of A673 cells. Inhibition of monocyte killing by this MAb was particularly pronounced at a low effector to target cell ratio. HT-29 cells were relatively resistant to the cytotoxic action of recombinant TNF and to monocyte killing. Treatment of HT-29 cells with recombinant human IFN gamma increased their susceptibility to both TNF cytotoxicity and monocyte killing. In addition, MAb to TNF inhibited monocyte killing in HT-29 cells sensitized by incubation with IFN-gamma. Our data show that TNF is an important mediator of the cytotoxicity of human monocytes for tumor cells and that IFN gamma can increase monocyte cytotoxicity by sensitizing target cells to the lytic action of TNF. PMID- 3098852 TI - The cytoplasmic expression of CD3 antigens in normal and malignant cells of the T lymphoid lineage. AB - Anti-CD3 (T3) Ab reacting with different proportions of thymocytes (anti-CD3a: UCHT1, anti-CD3b: T10B9, and anti-CD3c: OKT3) were tested for cytoplasmic (cCD3) and membrane (mCD3) expression in the bone marrow, thymus, and blood in man and selected primates. The expression of cCD3a and cCD3c in the perinuclear and Golgi area of large, BrdU-incorporating, strongly TdT+ thymic blasts probably represents one of the earliest signs of T cell commitment, because these blast cells are CD1-, CD4-, CD8-, and mCD3-. The cCD3+, TdT+ cells are normally restricted to the thymus and are absent among the TdT+ cells of bone marrow. The anti-CD3b Ab used, T10B9, co-caps and co-modulates with the other anti-CD3 Ab and is a T cell-specific reagent at a membrane level but does not bind to perinuclear cCD3. Instead, this reagent cross-reacts with a filamentous cytoplasmic network in non-T cells in man and in primates S. oedipus and M. rhesus despite their T cell negativity for mCD3. The characteristics of all T-ALL cases studied: cCD3+, CD7+ along with nuclear TdT+ suggest lineage fidelity to early thymic blasts. As a marked contrast, cCD3 is absent in common ALL and in AML, including cases that concomitantly express CD7 and myeloid antigens. Thus, the cCD3, TdT combination provides a very sensitive assay for residual T-ALL blasts outside the normal thymus. PMID- 3098853 TI - A competitive enzyme immunoassay of human beta 2-microglobulin based on separation by filtration. AB - A competitive enzyme immunoassay has been developed for the determination of beta 2-microglobulin in undiluted human serum. In the assay a beta 2-microglobulin beta-galactosidase conjugate competes with beta 2-microglobulin from the sample for the binding to anti-beta 2-microglobulin antibodies bound to small size agarose particles (micro-Sepharose) via a double antibody. The conjugate is made by providing beta 2-microglobulin with 'reactive disulphide structures.' This is achieved by the heterobifunctional reagent SPDP and the subsequent linkage of the formed derivative to beta-galactosidase by a thioldisulphide exchange reaction. This procedure gives conjugates with high immunoreactivity and enzyme activity. The assay is fast and simple. The reagents are incubated together for 60 min in the wells of a Millititer plate and separation is performed by filtration. Bound enzyme-labelled beta 2-microglobulin is measured by incubation with substrate for 15 min. Both incubations are performed at room temperature without agitation. Due to the high capacity of the micro-Sepharose no sample predilution is needed. The use of the Millititer filtration system gives a rapid and efficient separation and the advantages of access to equipment for dispensing and reading adapted to the microtitre format. PMID- 3098854 TI - Characterization and diagnostic application of a lipopolysaccharide core oligosaccharide-protein conjugate. AB - Shigella sonnei phase II core oligosaccharide (OSPhII) was linked covalently with protein (bovine serum albumin or tetanus toxoid) to obtain a conjugate (OSPhII protein) of good immunogenicity in rabbits. Anti-OSPhII-protein conjugate sera contained high levels of immunoglobulin G antibodies against the complete core region of Sh. sonnei lipopolysaccharide. The antigenic relationships between lipopolysaccharides of R1, R3 and R4 core types using anti-OSPhII-protein sera were studied. These antisera may be used for the rapid determination of core types in unknown enterobacterial strains. PMID- 3098855 TI - Human kappa light chain subgroup analysis with synthetic peptide-induced antisera. AB - All human kappa light chains belong to one of four subgroups, classified according to their amino acid sequences or by reactivity with adsorbed heteroantisera. The structural basis for the subgroup distinction by antisera is unknown. Therefore, to create anti-kappa subgroup antibodies with predefined specificity, we immunized rabbits with synthetic peptides which correspond to sequences within the first framework region of prototype kappa I, II, III, and IV light chains. The peptide-induced antisera recognized primary sequence-dependent kappa subgroup determinants. They correctly predicted the amino acid sequence in the first framework region of two kappa light chains. By Western immunoblotting and enzyme-linked immunoassay the antisera also identified previously typed, monoclonal light chains of different subgroups with complete specificity. These reagents, define a site of kappa subgroup distinction and represent a potent tool for the characterization of light chain heterogeneity. PMID- 3098857 TI - Atypical presentation of meningococcal meningitis. AB - We describe a case of meningococcal meningitis which presented as low-grade aseptic meningitis in an immunocompetent adult. Neisseria meningitidis Group B was isolated from cerebrospinal fluid in small numbers on two occasions 5 days apart, while blood cultures remained negative. PMID- 3098856 TI - Neonatal listeriosis due to cross-infection in an obstetric theatre. AB - Two cases of neonatal listeriosis following Caesarean section are reported. Evidence is presented which suggests that cross-infection took place in the obstetric operating theatre. The first case shows the features of early-onset disease while the second illustrates the late-onset pattern. Listeria monocytogenes was isolated also from the mother of the first baby. The two neonatal disease patterns are discussed. PMID- 3098858 TI - Primary meningococcal polyarthritis. AB - We report a case of primary meningococcal polyarthritis simulating bacteraemic gonococcal infection. The clinical similarity between extragenital gonococcal and meningococcal infections is well illustrated. If the clinical features of meningococcal and gonococcal infections are usually different, they may sometimes be indistinguishable. Both gonococcal pharyngitis and meningococcal urethritis have been recorded. The onset of acute polyarthritis, fever and skin lesions is typical of gonococcal infection but these clinical features may also indicate infection due to Neisseria meningitidis. In the case we report, the correct diagnosis of meningococcal arthritis was established only after N. meningitidis group C had been identified in synovial fluid from the knee. PMID- 3098859 TI - Serodiagnosis of Streptococcus faecalis endocarditis. PMID- 3098860 TI - Immunohistochemical localization of urokinase- and tissue-type plasminogen activators in psoriatic skin. AB - Biopsies of involved and uninvolved skin from psoriatic patients and of normal skin were stained immunocytochemically with monoclonal antibodies against urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activator using a multilayer peroxidase technique. Epidermis from psoriatic lesions showed focal staining for u-PA in and between the basal keratinocytes in the suprapapillary epidermal areas, while t-PA was found in the superficial keratinizing cells, including both stratum spinosum and the parakeratotic layer. No staining of keratinocytes was observed in uninvolved and normal skin. The specificity of the staining was supported by the finding that 3 different monoclonal antibodies and polyclonal antibodies against each of the plasminogen activators gave identical staining, while monoclonal antibodies of irrelevant specificity gave no staining. The present findings suggest abnormalities in the regulation of both types of plasminogen activators in psoriatic epidermis. PMID- 3098861 TI - Galactomannan antigenemia and antigenuria in aspergillosis: studies in patients and experimentally infected rabbits. AB - Purified galactomannan (GM) from Aspergillus fumigatus was used in both a radioimmunoassay and an enzyme-linked immunoassay for antigen detection. Results of the two tests seemed interchangeable. By one or both assays, GM was detected in serum from four of 12 rabbits lethally infected with A. fumigatus in concentrations ranging from 108 to 356 ng/ml. Serum antigen was detected in only two of 12 patients with invasive aspergillosis. Results of assay for GM in urine were far more encouraging. Urinary GM was detectable throughout the course of lethal aspergillosis in all 16 rabbits, in concentrations of 24-1,900 ng/ml. Urine from seven of 13 patients with invasive aspergillosis had GM concentrations of 1-83 ng/ml. Antigen excretion roughly paralleled extent of disease. PMID- 3098863 TI - Disseminated gonococcal infection caused by penicillinase-producing organisms in patients with unusual joint involvement. PMID- 3098862 TI - Characterization and use of a DNA probe as an epidemiological marker for Pseudomonas aeruginosa. AB - We used DNA restriction fragments, derived from the exotoxin A gene and surrounding sequences, as an epidemiological marker for Pseudomonas aeruginosa. Using these DNA fragments as probes in Southern blot hybridizations and/or total genomic digestions, we were able to distinguish greater than 100 different strains of P. aeruginosa. The stability of the marker in vitro was established by using well-characterized strains, which were stored under different conditions and subjected to chemical mutagenesis. The stability of the marker within a given strain in vivo was established during experimental infection in the chronic rat lung model of pseudomonas pneumonia. P. aeruginosa serially cultured from individual patients with cystic fibrosis were examined by using this marker. Isolates that varied in colonial morphology, serotype, and biotype were identical when analyzed by Southern blot hybridization using the fragment as a probe. Indistinguishable isolates (by serotyping, biotyping, and antibiograms) cultured from two unrelated patients were easily distinguished by using Southern blot analysis. PMID- 3098864 TI - An attenuated aroA Salmonella typhimurium vaccine elicits humoral and cellular immunity to cloned beta-galactosidase in mice. AB - beta-Galactosidase (GZ) is an intracellular protein that is frequently used to express cloned antigens as fusion proteins in Escherichia coli. Salmonella typhimurium strain SL3261, an attenuated aroA vaccine strain, was used as a carrier for the plasmid pXY411, which directs the expression of GZ in salmonellae (which do not normally produce this protein). The resulting strain- SL3261(pXY411)--expressed GZ as an intracellular antigen. The plasmid was stable in vitro and in vivo and did not significantly alter the behavior of strain SL3261 in mice. Animals intravenously vaccinated with this construct developed circulating antibodies to GZ, as measured by ELISA, and delayed hypersensitivity to the antigen injected in the footpad. These results indicate that attenuated salmonellae may be expected to elicit both humoral and cellular responses to intracellular cloned antigens. PMID- 3098866 TI - [Serological diagnosis of anti-Pseudomonas, anti-Klebsiella and anti-E. coli antibody by ELISA]. PMID- 3098865 TI - Biochemical studies on Mycobacterium leprae. AB - Very little information is available on the basic biology of Mycobacterium leprae. It is not known why the organism fails to grow in bacteriological media or in cell cultures and why it has an unusual predilection for certain tissues in the human host where cells derived from the neural crest occur (e.g. skin, peripheral nerves adrenal medulla). Biochemical studies have revealed that M. Leprae contains an unusual form of the enzyme diphenoloxidase which has not been detected in other mycobacteria. The presence of a specific glutamic acid decarboxylase in the organism has been demonstrated. Although a few enzymes of glycolysis and tricarboxylic acid cycle have been investigated, nothing characteristic of the bacterium has been discovered, and how M. leprae derives energy for its survival and proliferation still remains obscure. PMID- 3098867 TI - [Catalase-negative Citrobacter freundii isolated from the urinary tract]. PMID- 3098868 TI - [Review of clinical course of 51 fungemia]. PMID- 3098869 TI - [Whole blood chemiluminescence response and virulence of various organisms in systemic infection]. PMID- 3098870 TI - [Studies on Chlamydia trachomatis as the cause of respiratory infections. I. Prevalence of serum antibodies to Chlamydia trachomatis in healthy adults and patients with respiratory infections]. PMID- 3098871 TI - [Comparative study of cefuzonam (CZON) with cefmenoxime in chronic respiratory tract infections by the double-blind method]. PMID- 3098872 TI - [Comparative study of cefuzonam (CZON) with cefotiam in bacterial pneumonia and pulmonary suppuration]. PMID- 3098873 TI - [Abscess of Bartholin's gland caused by Neisseria mucosa]. PMID- 3098874 TI - Intracellular distribution of 73,000 and 72,000 dalton heat shock proteins in HeLa cells. AB - Intracellular localization of 73,000 and 72,000 dalton heat shock proteins (HSP73/72) in HeLa cells that were heat shocked or treated with chemical stressors was investigated using indirect immunofluorescent staining. The antiserum used specifically recognized the HSP73/72 in HeLa cells, and HSPs were increased by heating cells at 42 degrees C for 2 or 4 h and by prior treatment with chemical stressors (sodium arsenite, cadmium chloride, 8-hydroxyquinoline and ethanol). There was diffuse cytoplasmic staining at 37 degrees C, whereas nucleoli were stained brightly when cells were heated at 42 degrees C for 2 h. This rapid accumulation of HSP73/72 in the nucleoli was not inhibited by cycloheximide (50 micrograms/ml). Translocation of HSPs to the nucleoli was specific for heat because no translocation was induced by treatment with chemical stressors. When the cells were returned to 37 degrees C after heating, the HSPs in their nucleoli disappeared rapidly and diffuse cytoplasmic staining was present after 6-9 h. Our results suggest that the transient accumulation of HSP73/72 in HeLa cell nucleoli that is induced by heat shock is not correlated with the development of thermotolerance obtained in other cell systems. PMID- 3098875 TI - [EDTA-dependent pseudothrombocytopenia]. PMID- 3098876 TI - [Inhibitory effects of 1-hydroxethane-1, 1-bisphosphonate (HEBP) and hexametaphosphate on early calculus formation]. PMID- 3098877 TI - [A case of distal type of renal tubular acidosis associated with chrysotherapy]. PMID- 3098878 TI - [A case of IgD myeloma with meningeal and testicular involvement]. PMID- 3098879 TI - On-line expiratory CO2 monitoring. AB - The single breath test for carbon dioxide (SBT-CO2) is the plot of expired FCO2 or CO2% against expired volume. It can be monitored during anaesthesia and in the intensive care unit with modest additions to generally available equipment. This paper describes some aspects of a computer program for presenting SBT-CO2 during controlled ventilation, in particular, the corrections to the primary data necessary for scientific accuracy. Examples are given of how the use of SBT-CO2 has increased our understanding of factors which influence the arterial-end-tidal PCO2 difference (PaCO2-PE,CO2). PaCO2-PE, CO2 is, in a given individual, usually dependent on tidal volume and frequency. Changes in lung volume and manoeuvres such as opening the pleura also affect gas exchange. Monitoring CO2 elimination gives a measure of metabolic rate if ventilation and pulmonary perfusion are maintained. This facilitates ventilatory therapy in situations where CO2 production is greatly increased, e.g. sepsis and tetanus. On the other hand, if metabolism and ventilation are unchanged, a reduction in CO2 elimination implies reduced pulmonary perfusion. This can be seen during increased right-left shunting, such as in surgery in patients with congenital heart disease. PMID- 3098880 TI - Association of cholesterol concentrations in low-density lipoprotein, high density lipoprotein, and high-density lipoprotein subfractions, and of apolipoproteins AI and AII, with coronary stenosis and left ventricular function. AB - We examined the association of cholesterol levels in serum lipoprotein fractions, as well as of serum apolipoprotein-AI (apo-AI) and apo-AII levels, with coronary artery stenosis (CAS) and left ventricle function in a group of 43 patients with angina pectoris (33 men and 10 women) subjected to angiography. Cholesterol level in VLDL, LDL, HDL2, and HDL3 fractions was determined after separation of these fractions by density gradient ultracentrifugation. HDL-cholesterol is the sum of cholesterol in HDL2 and HDL3. Cineangiography yielded scores for CAS and for left ventricle ejection fraction (LVEF). On univariate regression CAS was correlated weakly with LDL-cholesterol (positive) and with HDL3-cholesterol and HDL cholesterol (negative), and more strongly with LDL-cholesterol/HDL-cholesterol (positive), but not with HDL2-cholesterol. LVEF was correlated positively with HDL3-cholesterol, HDL-cholesterol, apo-AI, and apo-AII. Of other "risk factors," none was correlated with CAS, and a history of previous myocardial infarction (PMI) was the only one significantly correlated with LVEF. CAS itself was also correlated negatively with LVEF. In multiple regression analysis with two or three independent variables, the relation of HDL(3)-cholesterol with CAS remained significant when other risk factors were taken into account. LVEF remained related positively with HDL(3)-cholesterol, apo-AI, or apo-AII, when either of them was tested in combination with other risk factors; of these only PMI made a significant independent contribution. Conclusions for this patient group (with low HDL-cholesterol): HDL3-cholesterol, and not HDL2-cholesterol, is informative for CAS; HDL(3)-cholesterol, apo-AI, or apo-AII, as well as CAS and PMI, are associated with LVEF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098881 TI - Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by cultured human endothelial cells: modulation by thrombin, endotoxin, and histamine. AB - Primary cultures of pooled endothelial cells obtained from four to six human umbilical cord veins were grown to confluency in M 199 cell culture medium containing 20% human serum. The secretion of tissue-type plasminogen activator antigen (t-PA Ag) and fast-acting plasminogen activator inhibitor activity (PA-I activity) was measured in the conditioned medium after incubation of confluent cultures with serum-free medium for 24 hours (1.5 ml/25 cm2 cell surface). The baseline production of t-PA Ag was 2.7 +/- 1.4 ng/ml (mean +/- SD) and of PA-I activity 36 +/- 18 IU/ml. Stimulation with thrombin resulted in a dose-dependent and time-dependent increase of the secretion of both components. At 1 NIH U thrombin per milliliter, a fourfold increase of t-PA Ag and a twofold increase of PA-I activity were observed. This effect was dependent on a free active site in thrombin and specific protein synthesis (inhibited by cycloheximide and dactinomycin) but unrelated to prostacyclin synthesis (no effect of aspirin or indomethacin). No free t-PA activity could be demonstrated on fibrin plates in conditioned medium from either stimulated or nonstimulated endothelial cell cultures. Endotoxin stimulation resulted in a specific secretion of PA-I activity but not of t-PA Ag, whereas histamine stimulation at concentrations of 0.1 to 1 mumol/L caused a specific secretion of t-PA Ag but not of PA-I. These findings indicate that the secretion of t-PA Ag and PA-I activity are not necessarily coupled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098882 TI - Proper hyperventilation technique for neuroanesthesia in Thai patients. PMID- 3098883 TI - Effects of tocainide on Purkinje fibers from normal and infarcted ventricular tissues. AB - The left anterior descending coronary artery was occluded in anesthetized dogs. Dogs were sacrificed after 24 hours and the experimental preparations, which included both normal and infarcted tissues, were dissected from the left ventricles. Effects of tocainide in concentrations of 15-40 mg/l on action potentials of Purkinje fibers from normal and infarcted zones were studied using conventional microelectrode techniques. In the normal zone cells, tocainide superfusion produced a significant decrease in maximum diastolic potential, action potential amplitude, action potential duration to 50% and 90% repolarization and the rate of phase O depolarization, and no significant change in effective and functional refractory periods. In the infarct zone cells, it produced a significant decrease in action potential amplitude and the rate of phase O depolarization, a significant increase in effective and functional refractory periods, and no significant changes in the other parameters. The unequal actions of tocainide resulted in selective depression of maximum diastolic potential and action potential duration to 50% repolarization in the normal cells only, reducing the disparity in these parameters between normal and infarcted tissues. Tocainide increased the refractoriness (ratio of effective refractory period to action potential duration) in both cell types but this change was greater in the infarct zone. This decreased disparity of membrane potential and repolarization combined with increased refractoriness may help to block the arrhythmias observed in infarcted preparations following closely coupled stimuli. PMID- 3098884 TI - Melanocyte-stimulating hormone and the regulation of tyrosinase activity in hair follicular melanocytes of the mouse. AB - Skin tyrosinase activity increases during hair growth in C3H-HeAvy mice and reaches higher levels in young (30- to 35-day-old) mice when the hair follicular melanocytes synthesize the black pigment, eumelanin, than in older (6-month-old) mice when they produce the golden yellow pigment, phaeomelanin. To examine the regulation of the melanocytes at these different stages we have compared the effect of alpha-MSH and other agents that act, through cyclic AMP-dependent mechanisms, on skin tyrosinase activity in both young and old mice during hair growth, initiated by plucking. Daily administration of alpha-MSH, isoprenaline or theophylline increased coat darkness, and skin tyrosinase activity in the younger mice 7-9 days after plucking, but they were ineffective in the older mice. Similarly alpha-MSH, 8-bromo-cyclic AMP or theophylline increased tyrosinase activity in skin explants from the younger mice incubated for up to 24 h but had no effect in explants from older mice. Cyclic GMP had no effect on tyrosinase activity in skin explants from both young and old mice. It is suggested that whereas cyclic AMP-dependent mechanisms may operate to regulate tyrosinase activity in the hair follicular melanocytes of younger mice that produce eumelanin these systems may not operate in the older mice when these melanocytes synthesize phaeomelanin. Phaeomelanin synthesis, unlike that of eumelanin, may not depend upon tyrosinase and its regulation by cyclic AMP and this could explain the low levels of this enzyme in the skin and its failure to respond to alpha-MSH and other activators of the cyclic AMP system during periods of phaeomelanin production. PMID- 3098885 TI - Dopaminergic inhibition of tyrosinase activity in hair follicular melanocytes of the mouse. AB - Bromocriptine, a dopamine agonist that blocks the secretion of MSH, inhibits melanogenesis in the hair follicular melanocytes of pubertal C3H-HeAvy mice. However, since this effect cannot be explained by a reduction in circulating alpha-MSH, we have examined the possibility that dopaminergic mechanisms may have a direct inhibitory effect on these melanocytes. Bromocriptine decreased tyrosinase activity in skin explants from 30- to 35-day-old mice that were growing dark hair. This decrease in tyrosinase activity was blocked by dopamine receptor antagonists, haloperidol or spiperone. The specific D2 agonist LY 171555 also inhibited tyrosinase activity in the skin explants in a dose-related manner and the effect was blocked by sulpiride, a D2-receptor antagonist. Neither bromocriptine nor LY 171555 had any effect on tyrosinase activity in skin explants taken from adult mice that were growing yellow hair. The D1-receptor agonist SKF 38393 had no effect on tyrosinase activity in skin explants from either group of mice. The present results support the idea that dopamine D2 receptor agonists have a direct inhibitory effect upon tyrosinase activity of hair follicular melanocytes of the C3H-HeAvy mouse. However, this effect was confined to periods of dark hair growth when the melanocytes produce eumelanin. The D2 agonists were ineffective in reducing tyrosinase activity during adult life when the melanocytes produce predominantly phaeomelanin. This suggests that different control mechanisms may operate in the hair follicular melanocytes during periods of eumelanin and phaeomelanin synthesis. PMID- 3098886 TI - Reproductive hormone secretion and spermatogenic function in thyroidectomized rams receiving graded doses of exogenous thyroxine. AB - This study aimed to obtain a better understanding of the relationship between circulating thyroxine (T4) concentrations and reproductive endocrine function in the ram. Mature Merino rams were thyroidectomized and supplemented with 0, 30, 100 and 300% of normal T4 for 10 weeks. Thyroidectomy had no apparent effect on spermatogenic function but interfered with sperm maturation, the latter being returned to normal by 30% T4 replacement. Circulating testosterone levels were reduced by thyroidectomy and restored to control levels by 30% T4; when T4 levels were supranormal (300%), circulating testosterone levels were again reduced. The lowered circulating testosterone levels in thyroidectomized rams occurred as a result of suppressed testosterone secretion from the testis, observed under basal conditions and also following LH-releasing hormone (LHRH) and human chorionic gonadotrophin injection. In thyroidectomized rams, sex hormone binding globulin (SHBG) levels were depressed without changes in testosterone clearance rate (TCR), while in rams with supranormal T4 levels, TCR was increased without changes in SHBG levels. Subnormal levels of T4 also restored to normal the reduced LH pulse frequency in thyroidectomized rams. Reduced LH pulse frequency, together with diminished LH release following LHRH injection in thyroidectomized rams, suggested effects of T4 at the hypothalamo-pituitary axis. The present study demonstrates that complete lack of thyroid hormones suppresses normal reproductive endocrine function in the ram, but that this can be restored to normal by 30% T4 replacement. The results support the theory that T4 plays a permissive rather than a regulatory role in reproductive function in males. PMID- 3098887 TI - Sexual dimorphism in immunoneutralization of bioactivity of rat and ovine inhibin. AB - Inhibin was partially purified from bovine follicular fluid using chromatography on immobilized Procion Red 3B and anion-exchange chromatography. Ovariectomized Texel ewes were immunized against the inhibin-containing fraction from the Procion Red 3B column and the immune response was subsequently boosted with similar fractions or with the preparation obtained from the anion-exchange column. The potencies of the resulting antisera were evaluated in an in-vitro bioassay system for estimating inhibin activity, using dispersed rat pituitary cells. The antisera were found to inhibit the bioactivity of inhibin preparations from ovarian follicular fluid of bovine, porcine, ovine or human origin, as well as inhibin activity in ovine testicular lymph and rete testis fluid, in culture media from rat granulosa and rat Sertoli cells and in homogenates of rat ovaries and testes. These results indicate that the inhibin molecules from several species contain a common bioactive moiety. The results also showed that the antiserum was more effective in neutralizing inhibin activity from ovarian than from testicular sources in both sheep and rat, indicating a sex-related difference in the inhibin molecules within a species. PMID- 3098888 TI - The roles of inhibin and gonadotrophin-releasing hormone in the control of gonadotrophin secretion in the ewe. AB - The respective roles and relative importance of ovarian inhibition and hypothalamic stimulation in the differential control of the secretion of FSH and LH were studied in the ewe. In the first experiment two groups of ten intact ewes were injected i.v. twice daily with 9 ml charcoal-extracted bovine follicular fluid (bFF), a preparation rich in inhibin (3.65 ku./ml), throughout the luteal phase of the oestrous cycle. Compared with the control ewes, this treatment significantly reduced pituitary and plasma FSH concentrations and increased the frequency and amplitude of the LH pulses, but did not affect pituitary LH concentrations. In a second experiment, five control and five bFF-treated ewes from experiment 1 were ovariectomized and the injection regime was altered to 2.5 ml s.c. every 8 h. This treatment was maintained for 21 days. In control ewes, plasma FSH concentrations rose significantly within 12 h and continued to rise for 3-4 days. Treatment with bFF abolished this increase and maintained plasma FSH concentrations below those observed in intact ewes. The rise in mean plasma LH concentrations evoked by ovariectomy was also partially inhibited in the bFF treated ewes. The response to the gonadotrophin-releasing hormone (GnRH) agonist buserelin (5 micrograms i.v.) was measured 6, 12 and 18 days after ovariectomy. In control ewes the agonist consistently evoked large surges of both hormones but in bFF-treated ewes the FSH response was completely blocked and the initial phase of the LH response (the first 'pool') was greatly reduced. In experiment 3, six ewes were ovariectomized and passively immunized against GnRH 3 days after oestrus. The increase in plasma LH which normally follows ovariectomy was completely abolished and mean concentrations remained very low and did not change over the following 14 days. In contrast, mean FSH concentrations rose significantly within 12 h of ovariectomy and continued to rise until the third day, after which they fell gradually. Treating three of the ewes with bFF (2.5 ml s.c. every 8 h) 8 days after ovariectomy and immunization further reduced the FSH concentrations. When the ewes were injected repeatedly (200 ng i.v., hourly for 5 h) with [D-penicillamine-(But)6]-GnRH(1-9)nonapeptide-ethylamide, a synthetic GnRH analogue which does not bind to the antiserum, there was a rapid rise in the secretion of LH in both control and bFF-treated animals but, as with the responses to buserelin, the initial response was significantly lower in bFF treated than in control ewes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3098889 TI - Developmental changes in gonadotrophins and testicular gonadotrophin receptors in the pig, from neonatal to adult life. AB - Changes in the concentrations of LH and FSH testicular receptors have been studied in the pig, from neonatal to adult life, and correlated with blood LH, FSH and testosterone concentrations. Quantification of gonadotrophin receptors was performed in equilibrium binding studies, using homologous systems. The presence of high-affinity binding sites for LH and FSH (association constant (Ka): LH approximately 20 litres/nmol; FSH approximately 10 litres/nmol) was demonstrated in the testes of all animals studied. The apparent affinity of LH and FSH receptors did not change significantly with age. During the first weeks of life, there was a transient rise in LH receptor content, reaching a maximum of 8.7 +/- 2.2 (mean +/- S.E.M.) pmol/g testis at 24 days of age. This was correlated with a peak in testosterone secretion and reflects the second wave of interstitial cell proliferation in the pig. A second increase in the number of LH receptors occurred after 12 weeks of age and corresponds to pubertal maturation and final differentiation of adult Leydig cells. During this period, circulating concentrations of testosterone markedly increased without any significant variation in LH blood levels, suggesting a change in testicular sensitivity to LH in the maturing pig. A continuous increase in FSH receptor content was observed from the neonatal to the adult pig. This increase occurred in two phases. During the first 2 months of life, the increase in the number of FSH receptors exceeded that of testis growth rate and resulted in an increase in FSH receptor concentrations which reached a peak at 12.1 +/- 1.8 pmol/g testis, at week 9.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098890 TI - Serotonin induces gonadotrophin release through stimulation of LH-releasing hormone release from the median eminence. AB - The effects of serotonin (5-HT) on the release of gonadotrophins and LH-releasing hormone (LHRH) were examined in an in-vitro perifusion system using median eminences and/or anterior pituitaries obtained from male or pro-oestrous female rats. Animals were killed by decapitation between 12.00 and 13.00 h. A serial double-chamber perifusion system was employed. Three types of experiments were performed. In the first, median eminences were placed in the first chamber and one anterior pituitary in the second chamber. In the second group, only the anterior pituitary was perifused. In the third group, only five median eminences were perifused. In the first and second experiments, LH, FSH and prolactin were determined in the perifusion efflux by radio-immunoassay (RIA). In the third experiment, LHRH was determined by RIA. Addition of 5-HT (final concentrations 0.06, 0.6 and 6.0 mumol/l) into the first chamber containing the median eminences stimulated the release of LH and FSH from the pituitary, but did not affect the levels of prolactin in the effluent in the same experiment (pro-oestrous rats). The stimulatory effect of 5-HT was blocked by the addition of cyproheptadine (l mumol/l) in the perifusion fluid. The introduction of 5-HT (0.6 mumol/l) into the tube connecting the first and second chambers did not modify the release of LH, nor did 5-HT added to the pituitaries perifused alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098891 TI - Changes in FSH and the pulsatile secretion of LH during treatment of ewes with bovine follicular fluid throughout the luteal phase of the oestrous cycle. AB - Treatment of Damline ewes with twice-daily i.v. injections of bovine follicular fluid during the luteal phase for 10 or 2 days before prostaglandin-induced luteolysis resulted in a delay in the onset of oestrous behaviour and a marginal increase in ovulation rate. During the treatment cycle, blood samples were withdrawn at 15-min intervals for 25 h from 08.00 h on days 1, 6 and 10 (day 0 = oestrus). At all three stages of the luteal phase, plasma FSH concentrations were suppressed relative to controls 3 h after the 09.00 h injection of follicular fluid and remained low until 06.00 h on the following day. In the 10-day treatment group LH pulse amplitude was significantly greater than that of controls on days 6 and 10. Pulse frequency remained high throughout treatment and was significantly higher relative to controls on day 10 despite normal progesterone levels. The results suggest that the higher pulsatile LH secretion during the luteal phase is due to reduced negative feedback effects of oestradiol occurring as a result of the follicular fluid-induced reduction in FSH. PMID- 3098892 TI - The MRC OX-44 antigen marks a functionally relevant subset among rat thymocytes. AB - A monoclonal antibody called MRC OX-44 is described that labels all myeloid cells and peripheral lymphoid cells but only 12% of thymocytes. The OX-44+ thymic cells include most if not all cells found in the medulla but only a small fraction of the cortical cells. Together with CD4 and CD8 antigens, seven subsets of thymic cell were defined and it was notable that most CD4- CD8- cells were OX-44+ whereas almost all CD4+ CD8+ cells were OX-44-. In functional tests, the OX-44+ cells accounted for all proliferation by thymocytes when stimulated by allogeneic spleen cells or concanavalin A plus growth factors and OX-44- cells were completely negative in these assays. Also, in tests for thymopoiesis after intra thymic injection of cells, all activity was OX-44+. It seems possible that the OX 44+ set may include all functionally relevant cells in the rat thymus. PMID- 3098893 TI - B cell stimulatory factor 1 (interleukin 4) is a potent costimulant for normal resting T lymphocytes. AB - Resting T cells proliferate in response to B cell stimulatory factor 1 (BSF-1; interleukin 4) plus phorbol myristate acetate (PMA). This response is obtained with highly purified T cells and is density independent, suggesting that accessory cells are not required. Both L3T4+ and Lyt-2+ T cells respond to BSF-1 plus PMA. Although BSF-1 alone does not cause T cell proliferation, it maintains the viability of small, dense T cells, indicating that it acts on resting T cells. Furthermore, BSF-1 is required early in the proliferative response of resting T cells to BSF-1 plus PMA, further supporting the concept that it acts on G0 or early G1 cells. However, BSF-1 is also needed late in the first round of division of T cells stimulated with BSF-1 plus PMA. Removing BSF-1 at 24 h of stimulation prevents entry into S phase. These results indicate that BSF-1 is involved in both the induction of competence and in the progression phases of T cell division. PMID- 3098894 TI - Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. AB - A cell line established from a patient with acute lymphoblastic leukemia was found to express IL-2 binding sites with a novel, intermediate affinity compared with the characteristic high-affinity IL-2-receptors and low-affinity IL-2 binding sites described previously. Clones were isolated from this cell line that displayed solely this new IL-2-binding protein, and were found to be unreactive with anti-Tac, the mAb that competes with IL-2 for binding. Moreover, these same cloned cells did not express mRNA detectable by hybridization with radiolabeled cDNA encoding the Tac protein. In contrast, the original cell line and similar clones expressed low levels of Tac mRNA and cell surface Tac antigen, both of which could be augmented by exposure to medium conditioned by adult T leukemia cell lines. Particularly noteworthy, induction of Tac antigen expression was paralleled by an increase in the number of high-affinity IL-2-R detectable. Since the expression of the Tac antigen protein by itself makes only for low-affinity IL-2 binding, these data prompted a reevaluation of the structural composition of high-affinity IL-2-R. Analysis of the IL-2-binding proteins expressed by leukemic cell lines lacking high-affinity receptors revealed only a single protein, larger than the Tac antigen protein (Mr = 75,000 vs. 55,000). In contrast, clones induced to express high-affinity receptors had clearly both of these IL-2-binding proteins. Moreover, when IL-2 binding to normal T cells was performed under conditions that favored the proportion of high-affinity receptors occupied, two distinct proteins identical to those already identified on the leukemic cells could be crosslinked covalently to radiolabeled IL-2. The interpretations derived from these varied, assembled data, point to two IL-2-binding proteins, both of which are required for high-affinity IL-2 binding. PMID- 3098896 TI - The cellular basis of the calcium dependence of GnRH-stimulated gonadotropin release from frog, Rana pipiens, pituitaries. AB - An in vitro superfusion system was used in an attempt to identify the cellular systems involved in the Ca2+ dependence of gonadotropin-releasing hormone (GnRH) actions in the frog, Rana pipiens. Superfusion with 5 microM A23187 (a calcium ionophore) or phorbol myristate acetate (an analog of diacylglycerides) caused marked increases in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Exclusion of Ca2+ from the medium prevented the stimulatory effects of PMA. The potent stimulator of adenylate cyclase, forskolin, caused only slight stimulation of LH and FSH secretion, which was also prevented by removal of Ca2+. The cytoskeletal disruptive agents colchicine, nocodazole, and cytochalasin B, and the calmodulin inhibitors, trifluoperazine and pimozide, had no significant effects on the action of GnRH. Overall, these results indicate that the major mechanisms of Ca2+ involvement in the response to GnRH by the frog pituitary are similar to that of mammals, with the possible exceptions of lesser roles for calmodulin and the cytoskeleton in the frog. The study suggests that polyphosphatidyl-inositol-diacylglyceride metabolism may be critical in understanding the mechanism of GnRH action in frogs. PMID- 3098895 TI - Human rheumatoid factor crossidiotypes. II. Primary structure-dependent crossreactive idiotype, PSL2-CRI, present on Wa monoclonal rheumatoid factors is present on Bla and other IgM kappa monoclonal autoantibodies. AB - The amino acid sequence of the L-CDR2 (complementarity-determining region) of Bla mRF (monoclonal rheumatoid factor) is identical to that of the Wa mRFs. The PSL2 CRI (crossreactive idiotype), as determined by anti-PSL2, which has been shown to be present on all Wa mRFs, is also present on the Bla mRF and other monoclonal autoantibodies. PSL2-CRI is, therefore, not unique to Wa mRFs and may be present on most IgM kappa monoclonal autoantibodies. Whether PSL2-CRI is a crossidiotype (XId) that is selectively present on autoantibodies or represents an allotypic marker for a V kappa III gene is undetermined. PMID- 3098898 TI - [Monoclonal macroglobulinemia with osteolytic lesions--a case report]. PMID- 3098897 TI - Prediction and detection of ovulation: a comparison of direct and indirect methods. PMID- 3098899 TI - Construction of a novel gene bank of Bacillus subtilis using a low copy number vector in Escherichia coli. AB - Low copy number vector plasmid pCT571 was constructed to clone Bacillus subtilis genomic fragments in Escherichia coli. pCT571 confers KmR, TcR and CmR in E. coli and CmR in B. subtilis. It has unique restriction sites within the KmR and TcR markers to allow screening for recombinant plasmids by insertional inactivation of these genes. It contains the pSC101 replicon and replicates normally at six to eight copies per chromosome equivalent in E. coli. It also contains oriVRK2, which when supplied with the product of the trfA gene of RK2 in trans, allows pCT571 to replicate at 35-40 copies per chromosome equivalent. A B. subtilis gene bank was created by cloning partially Sau3A-digested and size-fractionated fragments of B. subtilis chromosomal DNA into the BamHI site of pCT571. DNA from 1097 KmR TcS transformants was extracted and analysed electrophoretically as supercoiled DNA and after digesting with EcoRI or EcoRI and SalI. Approximately 1000 hybrid plasmids were found with reasonably sized B. subtilis fragments. The mean size of the inserts in pCT571 is 8 kb, ranging from 4 to 20 kb in different plasmids. The gene bank covers most of the B. subtilis chromosome, as demonstrated by the results of screening the gene bank for selectable nutritional markers in E. coli and B. subtilis. Hybrid plasmids which complement E. coli mutants for arg, his, lys, met, pdx, pyr and thr markers were identified from the gene bank. In B. subtilis the presence of argC, cysA, dal, hisA, ilvA, leuA, lys, metB, metC, phe, purA, purB, thr and trpC was established by transformation experiments. The effects of copy number on cloning and long-term maintenance in the bacterial strains were also investigated. At high copy number some hybrid plasmids cannot be maintained at all, while others show an increased rate of structural deletions and rearrangements. PMID- 3098900 TI - Isolation and characterization of a clone of the spoVE locus of Bacillus subtilis. AB - The Bacillus subtilis spoVE locus was isolated from a lambda clone bank and a 4.7 kbp EcoRV fragment subcloned into the shuttle vector pHV33. The resulting plasmid complemented chromosomal spoVE mutations. Its structure was stable in recE4 strains, but plasmid and chromosomal rearrangements occurred in rec+ strains. New spoVE mutations were obtained by mutagenesis of the plasmid; all the mutations tested mapped within three adjacent HindIII fragments of total length 1140 bp. PMID- 3098901 TI - Nucleotide sequence of the Bacillus subtilis developmental gene spoVE. AB - We have determined the nucleotide sequence of a 1159 bp DNA fragment containing the spoVE locus of Bacillus subtilis. The locus contained a single open reading frame of 293 codons. On the basis of the predicted amino acid sequence, the product of the spoVE gene is believed to be a protein with an Mr of 31,539. The amino-terminal portion of the spoVE gene was used to construct a translational fusion with the lacZ' gene. The hybrid spoVE-lacZ' gene was shown to be expressed in Escherichia coli and, therefore, it seems reasonable to conclude that the proposed open reading frame for the spoVE gene does indeed function in vivo. PMID- 3098902 TI - Enzyme-linked immunosorbent assay (ELISA) as a means of taxonomic analysis of Streptomyces and related organisms. AB - Fourteen Streptomyces strains from various numerical taxonomic classes and representatives of three other genera of actinomycetes were studied using an indirect enzyme-linked immunosorbent assay (IND-ELISA) to determine their serological relationships. The IND-ELISA results agreed with those from previous numerical taxonomic analyses and Ouchterlony double-diffusion studies. The IND ELISA method is quicker, more quantitative and less subjective than Ouchterlony assays and thus should be useful in Streptomyces taxonomy. The results indicated that Frankia sp. CpI1 was related to Streptomyces. PMID- 3098903 TI - Use of penicillin-binding proteins for the identification of enterococci. AB - The results of 20 physiological and fermentation tests and examination of the penicillin-binding proteins (PBPs) of 85 enterococcal strains demonstrated that the genus Enterococcus could be divided into at least nine distinct species: E. faecalis, E. faecium, E. durans, E. hirae, E. avium, E. gallinarum, E. casseliflavus, E. malodoratus and E. mundtii. Each species had a specific pattern of at least five PBPs, with molecular masses in the range of about 40-130 kDa. The pattern of PBPs may be useful for identification purposes, since some strains with unusual fermentation characteristics were assigned to species by this technique. PMID- 3098904 TI - Characterization of extracellular metallo- and serine-proteases of Aeromonas hydrophila strain B51. AB - The extracellular proteases of Aeromonas hydrophila B51 were stable on heating (56 degrees C) and on storage at 4 degrees C or -20 degrees C. Inhibitor studies showed that 72% of the total activity was inhibited by EDTA (a metalloprotease inhibitor) and 26% was inhibited by phenylmethanesulphonyl fluoride (a serine protease inhibitor). Analytical isoelectric focussing revealed the presence of 33 proteins in the crude extracellular products. Using a casein overlay technique three separate zones of proteolytic activity were detected: a zone with pI 6.5 6.8, formed of two closely focussed bands (possibly isomers of the same protease) and completely inhibited by EDTA; a single band with pI 7.0, which was inhibited by EDTA; and a diffuse zone with pI 8.3-8.5, which was only partially inhibited by EDTA. It is concluded that the serine protease activity focussed in this latter zone. These results indicate the presence of at least four, and possibly five proteases. Our results differ substantially from those reported by other workers using different isolates and it is suggested that significant differences in the character of extracellular products and extracellular proteases exist between different isolates of A. hydrophila. PMID- 3098905 TI - Genetic transformation of rifampicin resistance in Lactobacillus acidophilus. AB - Lactobacillus acidophilus strain 100-33, originally isolated from swine faeces, was transformed to rifampicin resistance with DNA from spontaneous rifampicin resistant mutants derived from it. Cells of the recipient strain were treated with lysozyme and mutanolysin, mixed with donor DNA and polyethylene glycol and grown on a regeneration medium overnight. After 48 h incubation, the numbers of rifampicin-resistant cells in the populations of regenerated cells were estimated from numbers of colonies. Efficiency of the lysozyme/mutanolysin treatment (the ratio of the number of osmotically fragile cells after the enzyme treatment to the initial cell number) was about 99%. The regeneration frequency of the enzyme treated cells varied from 5 to 67%. The transformation frequency varied from about 0.2 X 10(-8) to 8.0 X 10(-8) transformants per regenerated cell per microgram DNA. To our knowledge, this method for genetic transformation is the first to be reported for a Lactobacillus strain. PMID- 3098906 TI - A comparative study of acquired amidase activity in Pseudomonas species. AB - Pseudomonas putida PP3 carrying dehalogenases I and II and Pseudomonas aeruginosa PAU3 carrying dehalogenase I coded for by plasmid pUU2 were able to grow on 2 monochloropropionic acid (2MCPA). Neither strain utilized 2-chloropropionamide (2CPA) as a carbon or nitrogen source for growth. Mutations in both strains to 2Cpa+ phenotypes (designated P. putida PPW3 and P. aeruginosa PAU5, respectively) involved the expression of an acquired 2CPA-amidase activity. The amidase followed by dehalogenase reactions in these strains constituted a novel metabolic pathway for growth on 2CPA. P. putida PPW3 synthesized a constitutive amidase of molecular mass 59 kDa consisting of two identical subunits of 29 kDa. For those amides tested this acquired enzyme was most active against chlorinated aliphatic amides, although substrate affinities (Km) and maximum rates of activity (Vmax) were poor. P. aeruginosa PAU5 acquired a 2Cpa+ phenotype by overproducing the A amidase normally used by this species to hydrolyse aliphatic amides. The A amidase had only slight activity towards 2CPA. However, with constitutive synthesis the mutant grew on the chlorinated substrates. Chloroacetamide (CAA) was a toxic substrate analogue for these Pseudomonas strains. A strain resistant to CAA was isolated from P. aeruginosa PAU5 when exposed to 1-10 mM-CAA. This mutant, P. aeruginosa PAU6, synthesized an inducible A-amidase. CAA-resistance depended upon the simultaneous expression of CAA-inducible amidase and dehalogenase activities. PMID- 3098907 TI - beta-Galactosidase and alkaline phosphatase do not become extracellular when fused to the amino-terminal part of colicin N. AB - A series of plasmids encoding hybrid proteins comprising various lengths of the NH2-terminal region of colicin N coupled to almost complete beta-galactosidase or alkaline phosphatase polypeptides was constructed by transposon mutagenesis of ColN plasmid derivatives. Synthesis of the hybrid proteins, like that of colicin N itself, was regulated by the SOS response. Large quantities of the hybrid proteins accumulated in the cytoplasm (beta-galactosidase) or particulate fractions (alkaline phosphatase). When the gene fusions were expressed in cells that were producing colicin E2 and expressing the ColE2 lysis gene, only very low levels of the hybrid proteins were found in the medium. The results suggest that the amino-terminal part of colicin N does not contain sufficient biochemical information to promote the release of the hybrid proteins into the medium. PMID- 3098908 TI - A detailed study of gerJ mutants of Bacillus subtilis. AB - A total of nine gerJ mutants have now been isolated in Bacillus subtilis. All are defective in their spore germination properties, being blocked at an intermediate (phase grey) stage. The dormant spores are sensitive to heating at 90 degrees C and two of the mutants (generated by transposon insertion) produce spores sensitive at 80 degrees C. The spores of these two more extreme mutants had a visibly defective cortex when studied by electron microscopy, as did some of the other mutants. During sporulation, the acquisition of spore resistance properties and the appearance of the sporulation-specific penicillin-binding protein PBP5* were delayed. A strain probably carrying a lacZ fusion to the gerJ promoter demonstrated increased expression between t2 and t4. We propose that the gerJ locus is involved in the control of one or more sporulation-specific genes. PMID- 3098909 TI - Molecular cloning and nucleotide sequence of the alkaline cellulase gene from the alkalophilic Bacillus sp. strain 1139. AB - The cellulase gene from the alkalophilic Bacillus sp. strain 1139 was cloned in Escherichia coli using pBR322. Plasmid pFK1 was isolated from transformants producing cellulase, and the cloned cellulase gene was found to be in a 4 X 6 kb HindIII fragment. The cellulase gene was subcloned in a functional state on a 2 X 9 kb DNA fragment and its nucleotide sequence was determined. The coding sequence showed an open reading frame encoding 800 amino acids. The pFK1-encoded cellulase had the same enzymic properties as the extracellular cellulase produced by the alkalophilic Bacillus sp. strain 1139, but its Mr was slightly higher. PMID- 3098910 TI - Relaxation motions induced in Bacillus subtilis macrofibres by cleavage of peptidoglycan. AB - Bacillus subtilis macrofibres exposed to lysozyme underwent characteristic rotations, termed relaxation motions, in which their twist changed. Intact macrofibres and macrofibre fragments devoid of loop ends responded in the same way. Macrofibre strains for which the helix hand is temperature-dependent and also those of fixed-hand (both left and right) underwent initial relaxation motions towards the right-hand end of the twist spectrum, the only exception being those in which the initial twist state was at or near the right-hand maximum. Often when the initial relaxation motions were completed immediately before structure breakdown the macrofibres underwent one or a few rotations in the opposite direction (towards the left-hand end of the twist spectrum). Crude autolysin extract obtained from wild-type B. subtilis also caused macrofibre relaxation motions at pH 5.6 but at pH 8.0 macrofibre breakdown occurred as a result of septal cleavage. This resulted in the release of helically shaped individual cellular filaments. These findings suggest that strain in the cell wall associated with helical shape was dependent on the integrity of the glycan backbone rather than peptide cross-bridges. In contrast, cleavage of peptide cross-bridges apparently was instrumental in the cell separation process. Left- and right-hand macrofibres, when exposed to lysozyme, exhibited different rates of relaxation, breakdown of fibre structure and protoplast formation. Similarly, the rate of macrofibre breakdown during the lag between temperature shift and inversion reflected the replacement of septal wall material by that of a new conformation corresponding to the new helix hand.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098911 TI - O-acetylation of peptidoglycan in Neisseria gonorrhoeae. Investigation of lipid linked intermediates and glycan chains newly incorporated into the cell wall. AB - Radioactive labelling of the amino sugars in gonococcal peptidoglycan was followed by treatment with Chalaropsis muramidase and TLC separation of the products. Even after very brief periods of labelling (0.5 min) the peptidoglycan was already cross-linked to some 80% of the final value and little change occurred within 2 min. The remaining cross-linking was achieved only over a period of about one generation time. Streptomycete endopeptidase was used to show the extent to which new chains were cross-linked to old. Even at the earliest times many cross-linked units contained new material in both moieties and by 3 min there was little distinction in relative labelling, indicating that in Neisseria gonorrhoeae most newly synthesized glycan chains are cross-linked to other new chains rather than to pre-existing peptidoglycan. A model is proposed in which newly polymerized monomer units are predestined either towards dimer formation with other new chains, which are then rapidly O-acetylated and not further cross-linked, or towards the formation of trimers and higher oligomers, the latter being a slower process. Although significant O-acetylation of peptidoglycan was detectable even at the earliest times, efforts to detect O acetylated lipid intermediates were unsuccessful. The chief lipid intermediate found was apparently the disaccharide-peptide unit linked to undecaprenol. PMID- 3098912 TI - Agrobacterium Ti and Ri plasmids specify enzymic lactonization of mannopine to agropine. AB - A novel enzymic activity, responsible for the conversion of mannopine to agropine by lactonization, has been identified in Agrobacterium strains. This activity is encoded by octopine-type and agropine-type Ti or Ri plasmids, and is inducible by mannopine and agropine. In crude extracts it is stable for long periods and can be used for preparative synthesis of agropine from mannopine. The physiological role of this activity is not understood. However, it is probably involved in degradation of opines of the agropine family since it is always associated with agropine utilization in wild-type strains. PMID- 3098913 TI - Pyrimidine dimer excision repair of DNA in Bacteroides fragilis wild-type and mitomycin C-sensitive/UV-sensitive mutants. AB - An enzyme preparation purified from Micrococcus luteus was shown to be specific for UV-induced pyrimidine dimers and was suitable for the detection of DNA excision repair systems. The wild-type Bacteroides fragilis Bf-2 strain and a mitomycin C-sensitive mutant (MTC25) had constitutive dimer excision systems which functioned efficiently under anaerobic and aerobic conditions. A UV sensitive mutant (UVS9) had markedly reduced levels of the constitutive dimer excision systems under anaerobic and aerobic conditions. Since liquid holding recovery under aerobic conditions was inhibited by chloramphenicol whereas the final level of excision repair in B. fragilis Bf-2 was not affected, it is concluded that pyrimidine dimer removal is not the process responsible for increased physiological aerobic liquid holding recovery. PMID- 3098914 TI - Investigation of the regulation of the Escherichia coli btuB gene using operon fusions. AB - Operon fusions were isolated between Mu dX (lac CmR ApR) and btuB, the gene encoding the multivalent vitamin B12 outer membrane receptor. Using these fusions, vitamin B12-mediated repression of btuB in Escherichia coli was demonstrated. Mutations in metH, metE and ompR as well as exogenous methionine, membrane pertubants, high osmolar conditions and temperature had no major effect on the expression of the btuB gene. PMID- 3098916 TI - Adult-specific neurons in the nervous system of the moth, Manduca sexta: selective chemical ablation using hydroxyurea. AB - The segmental ganglia of adults of the moth, Manduca sexta, are constructed both from remodeled larval neurons and from adult-specific cells. The latter are produced by identified stem cells (neuroblasts) during larval life and then differentiate to form functional neurons during metamorphosis. The mitotic activity of the larval neuroblasts could be irreversibly blocked by the DNA synthesis inhibitor hydroxyurea (HU). Treatment on day 1 of the third larval stage resulted in 80-90% of the neuroblasts being blocked before they produced any progeny while leaving the functional larval neurons unaffected. Treated larvae finished growth, underwent metamorphosis, and produced an adult CNS that contained the normal set of remodeled larval neurons but lacked most of the new adult-specific cells. When HU treatment was delayed until the start of the fourth or fifth larval stage, the neuroblasts produced the early portions of their respective lineages before they were blocked. The immature neurons that were generated prior to treatment survived to contribute adult-specific neurons to the moth CNS, but the remainder of each lineage was missing. This technique therefore enables one to produce adult nervous systems containing the basic set of remodeled larval cells plus defined sets of adult-specific neurons. PMID- 3098915 TI - Fulminant hepatitis in asymptomatic hepatitis B surface antigen carriers in Greece. AB - Eleven male fulminant hepatitis (FH) patients (mean age: 47.7 +/- 16 years) positive for hepatitis B surface antigen (HBsAg) but negative for IgM antibody to hepatitis B core antigen (IgM anti-HBc) were admitted consecutively to the Athens Hospital for Infectious Diseases between May 1981 and November 1983. Because of the absence of IgM anti-HBc, determined by an enzyme immunoassay, these patients were considered to be HBsAg carriers with a superimposed acute hepatitis. Three of the 11 patients received immunosuppressive chemotherapy during the six months before the onset of the acute hepatitis. None of the patients was homosexual or a drug addict. Infection with hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis delta virus (HDV) was detected with serologic markers and/or molecular hybridization techniques. Fulminant hepatitis was attributed to spontaneous reactivation of chronic hepatitis B in four patients, chemotherapy-induced reactivation of chronic hepatitis B in three patients, HDV superinfection in one patient and possible superinfection by non-A, non-B agent(s), HDV, or HDV-like agents in three patients. Reactivation of chronic hepatitis B was an important cause of apparent acute hepatitis in heterosexual male HBsAg carriers from an area with a high prevalence of HBV infection. PMID- 3098917 TI - Cobalt blocks the decrease in MEPSP frequency on depolarization in calcium-free hypertonic media. AB - Media made hyperosmotic with sucrose increase the frequency of spontaneously released quanta of transmitter, or miniature excitatory postsynaptic potentials (MEPSPs). In calcium-free medium, depolarization with high potassium reduces the MEPSP frequency, presumably due to calcium efflux in the reversed gradient condition. This effect of depolarization is blocked by cobalt, supporting the above interpretation of the effects of hypertonicity and depolarization and suggesting that cobalt can block efflux as well as influx through calcium channels. PMID- 3098918 TI - myo-Inositol metabolism in 41A3 neuroblastoma cells: effects of high glucose and sorbitol levels. AB - Neuroblastoma cells were used to determine the effect of high carbohydrate and polyol levels on myo-inositol metabolism. The presence of elevated concentrations of glucose or sorbitol caused a significant decrease in both inositol accumulation and incorporation into phospholipid. These conditions, however, did not alter the accumulation of the other phospholipid head groups or the growth rate and water content of the cells. Two weeks of growth in either of the modified conditions was necessary to obtain a maximal effect on inositol incorporation. In contrast, growth in elevated concentrations of fructose, mannitol, or dulcitol had no effect on inositol metabolism. The reduced inositol accumulation and incorporation into lipids seen with glucose or sorbitol supplementation resulted in a decrease in the total phosphatidylinositol content of the cell without changing the levels of the other phospholipids. Kinetic analysis of cells grown in the presence of elevated glucose indicated that V'max for inositol uptake was significantly decreased with little change in the K'm. These data suggest that glucose decreases myo-inositol uptake in this system by noncompetitive inhibition. Cells grown in the presence of increased glucose also had elevated levels of intracellular sorbitol and decreased levels of myo inositol. These results suggest that the high levels of glucose and sorbitol which exist in poorly regulated diabetes may be at least partially responsible for diabetic neuropathy via a reduction in the cellular content of myo-inositol and phosphatidylinositol. This system may be a useful model to determine the effect of reduced inositol phospholipid levels on neural cell function. PMID- 3098919 TI - Biotin transport through the blood-brain barrier. AB - The unidirectional influx of biotin across cerebral capillaries, the anatomical locus of the blood-brain barrier, was measured with an in situ rat brain perfusion technique employing [3H]biotin. Biotin was transported across the blood brain barrier by a saturable system with a one-half saturation concentration of approximately 100 microM. The permeability-surface area products were 10(-4) s-1 with a biotin concentration of 0.02 microM in the perfusate. Probenecid, pantothenic acid, and nonanoic acid but not biocytin or biotin methylester (all 250 microM) inhibited biotin transfer through the blood-brain barrier. The isolated rabbit choroid plexus was unable to concentrate [3H]biotin from medium containing 1 nM [3H]biotin. These observations provide evidence that: biotin is transported through the blood-brain barrier by a saturable transport system that depends on a free carboxylic acid group, and the choroid plexus is probably not involved in the transfer of biotin between blood and cerebrospinal fluid. PMID- 3098920 TI - The metabolism of [18F]6-fluoro-L-3,4-dihydroxyphenylalanine in the hooded rat. AB - The metabolism of the positron-emitting compound [18F]6-fluoro-L-3,4 dihydroxyphenylalanine (*F-DOPA) was studied in carbidopa-pretreated male hooded rats. Thirty minutes following carbidopa administration (5 mg/kg i.p.), animals received *F-DOPA (500 micrograms/kg; specific activity, 175-230 Ci/mol) as an intrajugular bolus. Blood samples were taken at various times between 5 and 90 min, and the plasma was analyzed by HPLC with gamma counting of fractions. *F DOPA disappeared rapidly from plasma in concert with the formation of the 3-O methylated metabolite, Me-*F-DOPA. Animals were killed from 5 to 120 min after injection, and the brains were rapidly dissected. The disappearance of *F-DOPA from both vermis and striatal samples was rapid. Me-*F-DOPA, the sole metabolite observed in the vermis, was the major labeled material in the striatum at greater than or equal to 20 min after injection. Fluorodopamine was an important metabolite in the striatum, making up 25% of total radioactivity at early intervals. Striatal samples also contained fluoro-3,4-dihydroxyphenylacetic acid, which constituted approximately 10% of the total radioactivity, and traces of two radiolabeled compounds, tentatively identified as fluorohomovanillic acid and fluoro-3-methoxytyramine. PMID- 3098921 TI - Distribution of the two forms of monoamine oxidase within monoaminergic neurons of the guinea pig brain. AB - The relative distribution of type A and type B monoamine oxidase (MAO) inside and outside the monoaminergic synaptosomes in preparations from hypothalamus and striatum of the guinea pig was determined by incubation of synaptosomal preparations of these regions with low concentrations of [14C]5-hydroxytryptamine (5-HT), noradrenaline, and dopamine. The deamination within the monoaminergic synaptosomes was hindered by selective amine uptake inhibitors. In the absence of these inhibitors, both intra- and extraneuronal deamination was measured. The two forms of the enzyme were differentiated with the irreversible and selective MAO-A and MAO-B inhibitors clorgyline and selegiline (l-deprenyl), respectively. [14C]5 HT was deaminated greater than 90% by MAO-A both inside and outside the 5 hydroxytryptaminergic synaptosomes prepared from the guinea pig hypothalamus. The deamination of [14C]noradrenaline within the noradrenergic synaptosomes of the hypothalamic preparation was in the ratio 75:25% for MAO-A:MAO-B; the corresponding ratio outside these synaptosomes was 45:55%. The deamination of [14C]dopamine within dopaminergic synaptosomes in the striatal preparation was 65% type A:35% type B, whereas outside these synaptosomes the ratio was 35:65%. Because the relative amounts and the distribution of the two forms of MAO in the guinea pig brain seem to be similar to those previously detected for the human brain, the MAO in the guinea pig brain may be a good model for the MAO in the human brain. PMID- 3098922 TI - Phorbol ester enhancement of neurotransmitter release from rat brain synaptosomes. AB - Neurotransmitter release from rat brain synaptosomes was measured following pretreatment with various phorbol esters. Ca2+-dependent, evoked neurotransmitter release was increased by phorbol esters that were active in stimulating protein kinase C. Protein kinase C activation was demonstrated by increased incorporation of 32P into 87-kilodalton phosphoprotein, a specific substrate for that kinase. Inactive phorbol esters had no effect on neurotransmitter release or on the phosphorylation of 87-kilodalton phosphoprotein. The increased release was observed in either crude cortical synaptosomal fractions (P2) or purified cortical synaptosomal fractions. The enhancement was found for all neurotransmitters (norepinephrine, acetylcholine, gamma-aminobutyric acid, serotonin, dopamine, and aspartate), all brain regions (cerebral cortex, hippocampus, and corpus striatum), and all secretagogues (elevated extracellular K+ level, veratridine, or A23187) examined. It was also observed at all calcium concentrations present during stimulation of release. The phorbol ester enhancement of Ca2+-dependent release occurred whether or not calcium was present during pretreatment. These results indicate that stimulation of protein kinase C leads to an enhanced sensitivity of the stimulus-secretion coupling processes to calcium within the nerve terminal. The results support the possibility that presynaptic activation of protein kinase C modulates nerve terminal neurotransmitter release in the CNS. PMID- 3098923 TI - A comparative study of progabide, valproate, and placebo as add-on therapy in patients with refractory epilepsy. AB - A three way single blind cross-over comparison of progabide, valproate and placebo, as adjunctive therapy, was undertaken in 64 patients with therapy resistant partial and generalised seizures. The study was not completed because of the incidence of elevated hepatic enzymes on progabide. Analysis of efficacy showed progabide to be inferior to valproate against all seizure types, particularly against tonic-clonic seizures. Valproate was superior to placebo against all seizure types, partial and tonic-clonic seizures. Progabide did not differ significantly from placebo in any instance. In addition progabide caused elevation of hepatic enzymes which was symptomatic in one case, and was associated with an interaction with phenytoin which resulted in symptoms of intoxication in some cases. PMID- 3098924 TI - Intracranial calcified deposits in neurofibromatosis. AB - Three patients with the central type of neurofibromatosis, who on CT showed multiple subependymal calcified deposits, are presented. The literature on intracranial non-tumourous calcifications in neurofibromatosis is briefly reviewed. On the basis of our findings and the literature, it is proposed that such intracranial calcified deposits may be part of the neurofibromatosis syndrome and are caused by calcium deposits in glial proliferations, analogous to the calcified deposits seen in tuberous sclerosis. PMID- 3098925 TI - Action of thyrotropin-releasing hormone (TRH) on the occurrence of fibrillation potentials and miniature end-plate potentials (MEPPs). An experimental study. AB - The effect of TRH on fibrillation potentials and MEPPs were studied to determine the sites of action of TRH on muscle weakness. Intravenous administration of 10( 4) U thyroid-stimulating hormone (TSH) did not change the fibrillation-frequency of the denervated muscles of rats, but subsequent intravenous administration of 1 mg TRH did. Drip application of 0.6 mg TRH directly onto the denuded denervated muscles of rats did not cause an increase in fibrillation. Application of 1 mg TRH to the rat diaphragm increased the frequency of MEPPs. Both the increase in frequency of fibrillation potentials and the increase in frequency of MEPPs by application of TRH suggest that TRH influences nerve terminals, and that TRH seems suitable for treatment of muscle weakness in patients with ALS. PMID- 3098926 TI - Alzheimer's disease: Tau proteins, the promoting factors of microtubule assembly, are major components of paired helical filaments. AB - A rabbit antiserum was raised against paired helical filaments (PHF). This antiserum stains specifically neurofibrillary tangles (NFT) at the light microscopic level and PHF at the electron-microscopic level in sections of Alzheimer neocortex and hippocampus. We studied the nature of the antigens recognized by this antiserum by immunocytochemistry, immunoblots and immunoadsorption. These approaches showed that the anti-PHF specifically labels a set of low molecular weight 65-50 kDa microtubule-associated proteins, named Tau proteins, which are promoting factors of microtubule assembly. Furthermore, antisera against Tau proteins stained NFT. It is concluded that neurofibrillary tangles are very likely composed of aggregated Tau proteins. This process might be due to an abnormal Tau protein synthesis or to an unknown lesion of certain pyramidal neurons leading to an aggregation of Tau proteins. PMID- 3098927 TI - Concentrations of thyrotropin-releasing hormone in the brain of patients with amyotrophic lateral sclerosis. AB - Concentrations of thyrotropin-releasing hormone (TRH) were measured by a specific radioimmunoassay in the brain of 11 patients with amyotrophic lateral sclerosis (ALS) and 6 controls (myocardial infarction, gastric cancer, multiple myeloma, cerebrovascular disease, amyloid neuropathy). TRH was found in all parts of the dissected brain tissues (pedunculus cerebri, corpus callosum, capsula interna, motor area) in patients with ALS and controls. The TRH concentrations in the brain of patients with ALS were significantly lower in the pedunculus cerebri, compared with controls, and tended to decrease in the motor area and corpus callosum, but not significantly. Changes in TRH concentrations did not always correlate with pathohistological changes. These findings suggest that TRH is widely distributed in the human brain and decreases in some part of the ALS brain. PMID- 3098928 TI - Induction of 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells by gamma interferon. AB - Activity of the interferon-induced enzyme 2',5'-oligoadenylate (2-5A) synthetase was measured in peripheral blood mononuclear cells (PBMC) of 32 cancer patients treated with recombinant human gamma-interferon (rHGIF). Pretreatment activities varied widely but remained constant for each individual. The minimum dose of rHGIF that consistently stimulated activity was 12 MU/m2, although in some patients as little as 0.004 MU/m2 was stimulatory. Enzyme activity in responding patients increased threefold at 24 h after the initial infusion and remained elevated nearly twofold at 72 h independent of dose. This increase is less than that observed after infusions of alpha-interferon and parallels results observed in vitro. Pretreatment enzyme activity did not correlate with response. Twenty minute infusions of a fixed dose were as effective as four- and 24-h infusions in raising enzyme levels. The level of activity achieved after the initial infusion could not be sustained with twice-weekly infusions. We conclude that rHGIF does induce 2-5A synthetase activity in PBMC but not to the levels induced by alpha interferon. The observation that brief infusions of low doses can be maximally stimulatory in vivo suggests that the response of PBMC in vivo is being confounded by factors yet to be determined. Furthermore, it appears that the capacity of PBMC to maximally respond to rHGIF in vivo, with increases in enzyme activity, is transient. PMID- 3098929 TI - The mild hypertension dilemma: results of the British MRC trial. PMID- 3098930 TI - Perturbed pattern of catecholamine-containing neurons in mutant Drosophila deficient in the enzyme dopa decarboxylase. AB - We have initiated a study of catecholamine-containing neurons in Drosophila melanogaster because of the potential, with this organism, to perturb catecholamine metabolism using genetic tools. The major objectives of this study were (1) to define the pattern of catecholamine-containing neurons and (2) to determine the effect of the absence of dopa decarboxylase (DDC) enzyme activity on the catecholamine-containing neurons. We chose to analyze the catecholamine containing neurons in the ventral ganglion of the larval CNS. To define the catecholamine-containing neurons, CNSs were dissected and reacted with glyoxylic acid. The catecholamine histofluorescence (CF) neuronal pattern (normal-CF neurons) in the wild-type ventral ganglion is stereotypic. In the mutant ventral ganglia, in the absence of DDC enzyme activity, most normal-CF neurons still exhibit CF, probably indicating the presence of accumulated L-dopa. Interestingly, in the mutant CNSs, additional novel neuronal subsets also exhibit CF. Analysis of CNSs from early developmental stages revealed that the novel-CF neurons become fluorogenic earlier than the normal-CF neurons in the mutant CNS. To determine whether neuronal subsets, in addition to the normal-CF, neurons are able to sequester catecholamines, CNSs from wild-type larvae were incubated in exogenous catecholamine (L-dopa or dopamine). Incubations in L-dopa or dopamine revealed normally nonfluorogenic neurons that are able to take up the amine and become fluorogenic. Among the neurons able to sequester L-dopa or dopamine are subsets that are similar to the novel-CF neurons in the mutant CNS. This similarity is best characterized by a major novel-CF neuronal cluster in the subesophageal-thoracic region. These results suggest that in the absence of DDC activity, subsets of normally nonfluorogenic neurons capable of sequestering L dopa or dopamine accumulate the fluorogenic catecholamine. Hypotheses that might explain the mode of accumulation of the catecholamine within the novel-CF neurons are considered. PMID- 3098932 TI - Intra-arterial chemotherapy by cisplatin and cytarabine after temporary disruption of the blood-brain barrier for the treatment of malignant gliomas in adults. PMID- 3098931 TI - Biochemical and physical analyses of newly synthesized muscarinic acetylcholine receptors in cultured embryonic chicken cardiac cells. AB - Exposure of cultured embryonic chicken cardiac cells to the muscarinic agonist carbachol results in a 70-80% decrease in the number of muscarinic acetylcholine receptors (mAChR) expressed on the surface of the cells. Removal of the agonist results in a gradual increase in mAChR number because of the accumulation of newly synthesized receptors, reaching the control level in 14 hr. Measurements of increases in K+ permeability elicited by carbachol show that even after the complete recovery of receptor number, the sensitivity to agonist is reduced. The EC50 for carbachol is 13-fold higher in cells that have been exposed to carbachol and allowed to recover for 18 hr than in control cells, but is not significantly different from the EC50 for control cells 24 hr after agonist removal. The sensitivity of the mAChR-mediated inhibition of adenylate cyclase is also decreased at 18 hr, and recovers by 24 hr. These increases in sensitivity of mAChR-mediated responses are not blocked by administration of cycloheximide, and thus do not require de novo protein synthesis. The number of surface mAChR available for ligand binding can be reduced by 85-100% by treatment with the affinity-alkylating antagonist propylbenzilylcholine mustard. Newly synthesized mAChR that appear following affinity alkylation are also poorly coupled to mAChR mediated increases in K+ permeability, indicating that decreased physiological sensitivity is not due to a nonspecific effect of long-term agonist exposure on general cellular function, but reflects, rather, an intrinsic property of newly synthesized mAChR. The decrease in sensitivity of the mAChR-mediated responses is due neither to a lack of expression of mAChR on the surface nor to reduced agonist affinity of the mAChR. Cells exhibiting decreased responsiveness contain GTP-binding proteins, which function normally in the inhibition of adenylate cyclase and appear to be identical to pertussis toxin substrates from control cells using gel electrophoresis; therefore, the decreased sensitivity does not appear to be the result of an alteration in coupling proteins. These cells also contain mAChR that do not differ from those in control cells either by molecular weight or isoelectric point. Thus, the diminished sensitivity observed in cells containing newly synthesized receptors is either caused by a small change in mAChR not detected by these electrophoretic techniques or by a change in an as yet-undefined component of mAChR transduction system in the heart. PMID- 3098933 TI - Mechanism of ionophoric transport of indium-111 cations through a lipid bilayer membrane. AB - The use of mobile ionophores to facilitate the transport of 111In through a lipid bilayer membrane has broad applications in liposome technology and cell labeling. However, the mechanism of such ionophore-mediated transport of 111In through a lipid bilayer membrane is not completely clear. The present report describes the correlations of the behaviors of ionophoric loading of 111In into liposomes with the lipophilicity and the indium-binding affinity of three ionophores, namely, 8 hydroxyquinoline, acetylacetone, and tropolone. Our results suggest that the mechanism of the ionophoric transport of 111In through a lipid bilayer membrane involves the rapid exchange of 111In cations among the ionophores in both the aqueous solution and the lipid bilayer. Furthermore, the effectiveness of an ionophore in facilitating the transport of 111In from the external aqueous compartment to the entrapped nitrilotriacetic acid depends not only on the lipophilicity of the [111In]ionophore complex, but also on the lipophilicity of the free ionophore itself and the competition of 111In between nitrilotriacetic acid inside the inner aqueous compartment of the liposome and the ionophore imbedded in the lipid bilayer membrane of the liposome. PMID- 3098934 TI - Alteration in lipoprotein composition with intravenous compared to intragastric fat-free feeding in the rat. AB - Rats were fed continuously for 7 d with fat-free total parenteral nutrition solutions delivered intravenously (IV) or intragastrically (IG) to determine changes in plasma lipoprotein composition due to elimination of intestinal nutrient absorption. IV feeding resulted in significantly lower plasma levels of apoA-I and A-IV, which are synthesized by the intestine, and in a 40% reduction in the weight of intestinal mucosa. Higher apoE levels in plasma, a greater proportion of apoE-enriched HDL1 particles and proportionately more HDL cholesterol were observed in IV- than in IG-fed animals. IV feeding also resulted in lower apoC-II levels in the HDL fraction. These differences in plasma apolipoprotein and HDL composition suggest alterations in lipoprotein metabolism with IV compared to IG feeding in the rat. PMID- 3098935 TI - Effect of beta-carotene and canthaxanthin on the immune responses of the rat. AB - Male Wistar Kyoto rats were fed diets containing either 2 g/kg (0.2%) beta carotene, canthaxanthin or basal diet for up to 66 wk. Plasma and tissues were analyzed for vitamin A, vitamin E, beta-carotene or canthaxanthin levels. In vitro immune responses of splenocytes to T- and B-lymphocyte mitogens were determined. T- and B-lymphocyte responses were consistently enhanced in the groups fed beta-carotene or canthaxanthin. Since canthaxanthin cannot be converted to vitamin A, the immunoenhancement seen in these experiments is attributed to a carotenoid effect. PMID- 3098936 TI - Ascorbic acid requirement for the induction of microsomal drug-metabolizing enzymes in a rat mutant unable to synthesize ascorbic acid. AB - We investigated the requirement of ascorbic acid for the induction by polychlorinated biphenyls (PCB) of hepatic drug-metabolizing enzymes in ODS-od/od rat (OD rat) which is a rat mutant unable to synthesize ascorbic acid. ODS- +/+ rats (+/+ rat), which can synthesize ascorbic acid, were used as controls. In OD rats, the dietary requirement of ascorbic acid to maintain normal growth and prevent any signs of scurvy is about 300 mg of ascorbic acid per kilogram diet. In this study, dietary levels of ascorbic acid tested were 0, 50, 300, 1000 and 3000 mg ascorbic acid per kilogram diet with or without 200 mg of PCB per kilogram diet. Feeding PCB did not affect growth in rats of either genotype. When statistical analysis was done within groups fed diets without PCB, ascorbic acid deficiency caused significant decreases in body weight gain, hepatic activities of drug-metabolizing enzymes and level of hepatic cytochrome P-450. When OD rats were fed a diet without PCB, the supplementation of about 300 mg ascorbic per kilogram diet was sufficient to maintain normal activities of hepatic aminopyrine N-demethylase, aniline hydroxylase, cytochrome c reductase and reduction of cytochrome P-450 and a normal level of hepatic cytochrome P-450. However, when OD rats were fed a diet supplemented with 200 mg PCB per kilogram of diet, significantly higher activities of hepatic aminopyrine N-demethylase and aniline hydroxylase and significantly higher level of hepatic cytochrome P-450 were observed in OD rats fed a diet supplemented with 1000 mg or 3000 mg ascorbic acid per kilogram of diet than in rats fed a diet supplemented with 300 mg of ascorbic acid. It is concluded that the dietary requirement of ascorbic acid is increased severalfold by the administration of xenobiotics, such as PCB, for the maximum induction of hepatic drug metabolism. PMID- 3098937 TI - Effects of dietary protein, fat and energy intake during an initiation phase study of 7,12-dimethylbenz[a]anthracene-induced breast cancer in rats. AB - A factorial experiment was conducted to examine the effects of dietary protein (8, 16, 32% of energy from casein) and dietary fat (12, 24, 48% of energy from corn oil) on the initiation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast carcinogenesis in rats. Forty weanling female Sprague-Dawley rats were assigned to each of nine diets fed ad libitum. After 4 wk each rat received DMBA (20 mg/kg) via gastric intubation. For an additional 22 wk after carcinogen administration all rats consumed a diet containing 16% of dietary energy from protein and 24% from fat. Dietary fat, protein and ad libitum energy consumption exhibited statistically significant effects on final tumor prevalence, but interactive effects were not found. At necropsy, rats fed corn oil at 12, 24 and 48% of energy prior to DMBA administration showed tumor prevalences of 58, 58 and 85% with 116, 153 and 231 total tumors, respectively. The data indicate a significant nonlinear effect of dietary fat. Corresponding numbers for rats fed casein at 8, 16 and 32% of energy prior to DMBA were prevalences of 79, 65 and 59%, with total tumor counts of 194, 144 and 162. Higher dietary protein during the initiation phase was associated with a significant reduction in tumor prevalence, which was most striking between 8 and 16% of energy from protein. In addition, results of multiple logistic regression showed that tumorigenesis was increased with greater ad libitum energy intake. The odds of a tumor at necropsy were multiplied by 1.19 for each kilocalorie increase in ad libitum energy intake averaged over the post-DMBA phase of the experiment. An additional six weanling rats fed each diet for 4 wk were killed for assay of hepatic carcinogen metabolizing enzymes at the time corresponding to DMBA administration in the initiation experiment. Both protein and fat showed independent effects on the activity of several enzymes. However, enzyme activity did not suggest a unifying mechanism whereby these nutrients influence DMBA-induced mammary carcinogenesis. PMID- 3098938 TI - Effects of undernutrition during suckling on phosphoryl-serine levels in brain nuclear proteins of adult rats. AB - The effect of undernutrition during suckling on neurochemical and behavioral parameters were investigated in adult rats. Young rats were undernourished by suckling their lactating mothers fed an 8% (by wt) protein diet. Mothers of normal rats were fed a 20% protein diet. After weaning (d 21), normal and undernourished rats were fed a 20% protein diet until 90-120 d of age, when the rats were subjected to a short shuttle avoidance session and/or killed for neurochemical analyses. During shuttle avoidance sessions, footshock escape and footshock avoidance responses were analyzed simultaneously using 0.2- or 0.8-mA footshock intensity. In addition, the effect of undernutrition during suckling on phosphoryl-serine (P-Ser) level in brain nuclear proteins and the response of this level to a shuttle avoidance session were studied. We observed that undernutrition during suckling had no effect on footshock avoidance responses and decreased the latencies of footshock escape responses using 0.2-mA footshock intensity. Undernutrition decreased the basal level of P-Ser in brain nuclear proteins and abolished the decrease of this level observed in a shuttle avoidance session in normal rats using 0.2- or 0.8-mA footshock intensity. PMID- 3098939 TI - Potentiation of carcinogenesis by dietary fat: is it caused by high energy consumption or is it an effect of fat itself? PMID- 3098940 TI - Cost-effective choice of antimicrobial therapy for serious infections. AB - The authors evaluated the financial and health implications of treatment choices for three serious classes of infection: hospital-acquired pneumonia, intra abdominal infection, and sepsis of unknown origin. Data were obtained from a systematic review of clinical literature and published data bases, by written questionnaire from a panel of infectious disease authorities, and from actual costs at a tertiary-care hospital. For pneumonia and sepsis, the third-generation cephalosporin evaluated (ceftizoxime) was found to be less expensive than other regimens, when costs of dose preparation and administration, monitoring, and toxicity were added to drug acquisition costs. The lowest-cost regimen for intra abdominal infection was metronidazole plus gentamicin. Modest differences in efficacy would easily outweigh differences in toxicity, however, and could justify the use of more expensive regimens (e.g., mezlocillin plus gentamicin for hospital-acquired pneumonia, and cefoxitin plus gentamicin for intra-abdominal infection). If all regimens are assumed to be equally efficacious, then the third generation cephalosporin was both lowest in cost and, owing to its low toxicity, greatest in net health benefit. PMID- 3098942 TI - Use of capnography and transcutaneous oxygen monitoring during outpatient general anesthesia for oral surgery. AB - The combination of the capnograph (respired CO2 monitor) and the transcutaneous oxygen monitor was evaluated as a non-invasive system for monitoring of respiratory function in 10 ASA class I patients undergoing ultralight general anesthesia for removal of third molars. Capnography proved to be a sensitive and accurate method for detecting apnea and airway obstruction using the continuous display of the CO2 waveform. All episodes of apnea or obstruction were immediately detected as the respired CO2 level fell to zero baseline. The end tidal CO2 (PetCO2) obtained via nasal prong sampling was not significantly different from the PaCO2. PetCO2 values served as useful indicators of hypoventilation. During steady-state conditions of respiration, transcutaneous oxygen tensions (PtcO2) correlated well with simultaneously measured PaO2 (r = 0.93). However, during any period when oxygenation was rapidly changing (step increase in FIO2, step decrease in FIO2, or apnea) the PtcO2 lagged behind changes in PaO2 even after a five-minute equilibration period, thereby not accurately reflecting the true state of oxygenation. Consequently, the transcutaneous oxygen monitor does not appear to be optimal as a respiratory monitor in the setting of ultralight general anesthesia where rapid, critical changes in oxygenation must be detected without delay. PMID- 3098941 TI - Venous thromboembolism: epidemiology, diagnosis, prevention. PMID- 3098943 TI - The effect of chronic inflammation on gingival connective tissue proteoglycans and hyaluronic acid. AB - Proteoglycans have been isolated and analysed from extracts of normal and chronically inflamed human gingiva in order to determine the effects of chronic inflammation on these important soft connective tissue extracellular macromolecules. The uronic acid content of glycosaminoglycans isolated by papain digestion of normal and inflamed gingiva did not differ significantly. Likewise, electrophoretic analysis revealed that the content of hyaluronic acid, heparan sulfate, dermatan sulfate and chondroitin sulfate was similar. The sulfated glycosaminoglycans from both sources eluted from a Sepharose C1-6B column with a Kav of 0.45 (approximate Mr 25,000). However, hyaluronic acid from normal gingiva was predominantly of a large size eluting in the void volume of a Sepharose. CL 6B column, while that isolated form inflamed tissue was mostly a small molecular weight species which eluted in the included volume of a Sepharose CL-6B column. Using dissociative conditions, intact proteoglycans could be more readily extracted from inflamed tissues (90% of the total tissue uronic acid) than from normal tissues where only 80% of the total tissue uronic acid was extractable. Even though DEAE-Sephacel ion-exchange chromatography revealed no differences in charge between normal and inflamed gingival proteoglycans, Sepharose CL-4B chromatography revealed more molecular size polydispersity in samples from inflamed tissue than from normal tissue. Taken together, these results indicate that while hyaluronic acid is depolymerized in inflamed tissue, no evidence of sulfated glycosaminoglycan degradation was found. Therefore, the most likely cause for disruption to the molecular integrity of the proteoglycans is via proteolytic alteration to the proteoglycan core protein. PMID- 3098944 TI - Epithelial mitotic activity during the induction of palatal candidosis in the Wistar rat. AB - Palatal candidosis was produced in 15 Wistar rats by fitting them with an acrylic appliance that covered the palatal mucosa and simultaneously inoculating this site with Candida albicans 3091 (serotype A). A further 15 rats were fitted with the appliance only. Five animals in each group were killed at 1, 2 and 4 weeks, 4 X 5 h after being injected with vinblastine sulphate, as were 5 normal control animals at the start of the experiment. Palatal mucosa was dissected free, fixed, sectioned and stained prior to counting the number of arrested mitotic figures in the basal epithelial layer and measuring the mean thickness of epithelium. The results were expressed as the number of mitotic figures per 1000 basal cells, per unit length of basement membrane and per square millimetre of epithelial surface. After an initial reduction in thickness, the palatal epithelium in both experimental groups became thicker than that of normal control animals, more markedly so in the animals infected with Candida albicans. Similar patterns of mitotic activity were found regardless of the reference unit used as a basis for the calculations. An initial decrease in both experimental groups was followed by a sharp and significant rise, again being more marked in the animals infected with Candida albicans. PMID- 3098945 TI - A comparison of oral rinse and imprint sampling techniques for the detection of yeast, coliform and Staphylococcus aureus carriage in the oral cavity. AB - The sensitivity of the impression culture, the neat rinse culture (NRC) and the concentrated rinse culture (CRC) methods in detecting the oral carriage of yeasts, coliforms and Staphylococcus aureus was estimated in 75 individuals. The recovery of organisms from the imprint cultures of the tongue and the CRC was similar and there was highly significant positive correlation between the two techniques. The CRC was simple to perform, equally sensitive and superior in quantifying yeast, coliform and S. aureus carriage than the imprint culture technique. Hence, it is suggested that the CRC technique be preferentially employed in future investigations to obtain comparable data from different centres. PMID- 3098946 TI - Reversible valproate fulminant hepatic failure. AB - Valproate fulminant hepatotoxicity, usually fatal, is believed to be idiosyncratic and metabolic without an immunologic basis. There are no previous reports of a hypersensitivity reaction among numerous cases of fatal valproate fulminant hepatitis. Little is known about the electron microscopical features of valproate hepatitis. We report a case of reversible fulminant hepatitis attributable to valproate with clinical and histological characteristics of a hypersensitivity reaction. Electron microscopical findings included microvesicular steatosis with normal-appearing mitochondria. PMID- 3098947 TI - Long-term home parenteral nutrition in pediatrics: ten years of experience in 102 patients. AB - One hundred two pediatric patients received all or part of their nutritional needs parenterally at home during the past decade. All received total parenteral nutrition (TPN) at night during an 8- to 12-h infusion. Patients with short bowel syndrome (33%), inflammatory bowel disease (23%), chronic intractable diarrhea (15%), chronic idiopathic intestinal pseudo-obstruction syndrome (10%), and malignancy (10%) made up the largest groups. The mean duration of parenteral support was 735 days (range, 90-3650 days); the mean number of catheters per patient was 2.1 (range, 1-8). Twenty-one patients continue to receive full or partial home TPN: four for more than 10 years and seven for more than 5 years. Fifty-one no longer require it and have had healing of mucosa or bowel adaptation. Complications related to administration of fluid and electrolytes were quite rare. Biotin deficiency was recognized once. Thirty-one have died, but only 13 deaths were related to TPN. Sepsis in nine and liver failure in two were the most common causes of death in the TPN-related group. Three of 21 still on home TPN have graduated either from high school or college. All but one of the school age children attend regular school; one attends a school for the medically disabled, another attends a school for the mentally gifted. PMID- 3098948 TI - Comparison of serum fibronectin, prealbumin, and albumin concentrations during nutritional repletion in protein-calorie malnourished infants. AB - Anthropometric measurements and serum fibronectin, prealbumin, and albumin concentrations were determined on admission and during the hospitalization of 20 noninfected infants with protein-calorie malnutrition. Serum fibronectin concentrations were significantly decreased on admission but increased to greater than normal serum values in 2 weeks. During this same interval, serum prealbumin values rose from significantly decreased to normal levels. Serum albumin concentrations and anthropometric measurements were not significantly elevated above admission levels until the fourth week of nutritional support. Serum fibronectin and prealbumin concentrations may serve as indices of the short-term efficacy of nutritional support in noninfected infants with protein-calorie malnutrition. PMID- 3098949 TI - Home parenteral nutrition in chronic intestinal diseases: its effect on growth and development. AB - Nine children and adolescents with chronic intestinal diseases and growth failure were treated with home parenteral nutrition (HPN) for 7-63 months. All patients improved their growth velocities on HPN, with an average height gain of 9 cm. The mean growth velocity in six patients with Crohn's disease increased more than fivefold (from 0.67 +/- 0.4 cm/year to 3.8 +/- 1.09 cm/year), and they gained a mean of 11.4 +/- 3.4 kg/year. The three patients without Crohn's disease [intestinal pseudo-obstruction (two), severe short bowel (one)] increased growth velocity from an average of 2.9 +/- 1.1 cm to 6.1 +/- 1.34 cm/year and gained a mean of 10 +/- 2.84 kg/year. Patients without Crohn's disease grew faster on HPN than age comparable patients with Crohn's disease. Also, the two patients with Crohn's disease who were younger and had their disease for a shorter period (less than 3 years) grew better than older patients with Crohn's disease who had their disease for a mean of 8 +/- 1.3 years. All patients improved clinically, and three with Crohn's disease achieved complete remission. Five of the nine patients had psychosocial adjustment problems while on HPN. In conclusion, HPN is a relatively safe and effective means to stimulate growth in children and adolescents who cannot meet nutritional needs by the enteral route. PMID- 3098950 TI - Parenteral nutrition for infants: effect of high versus low calcium and phosphorus content. AB - Calcium (Ca) and phosphorus (P) homeostasis were determined in 18 infants (birth weight, 2,810 +/- 135 g; gestational age, 37.4 +/- 0.5 weeks; mean +/- SEM) who received high or low Ca and P content (Ca, P) parenteral nutrition (PN) with a fixed, low dose of vitamin D (25 IU/dl). Nine infants were randomized into low (standard) Ca, P (20 mg Ca and 15.5 mg P/dl) and nine into high Ca, P (60-80 mg Ca and 46.5-62 mg P/dl) PN, and then were studied for up to 6 weeks. The high Ca, P group had stable serum 1,25 dihydroxyvitamin D [1,25(OH)2D], which consistently remained within the normal range (less than 116 pg/ml). Tubular reabsorption of phosphorus (TRP) also was stable and remained consistently less than 90%. The low Ca, P group had elevated and higher 1,25(OH)2D (p = 0.03) than the high Ca, P group. The mean serum 1,25(OH)2D concentration rose from 32 to 112, 115, and 133 pg/ml over a period of 6 weeks. TRP also was higher (p = 0.02) and remained consistently greater than 90%. There were no significant differences between groups in serum parathyroid hormone, calcitonin, Ca, Mg, P, alkaline phosphatase, vitamin D binding protein, and 25 hydroxyvitamin D concentrations; urine Ca/creatinine and Mg/creatinine ratios, and fractional excretion of sodium (Na). Thus, a "high" Ca (60 mg/dl) and P (46.5 mg/dl) content in PN solutions can result in stable serum 1,25(OH)2D and TRP, presumably reflecting minimal stress to Ca and P homeostatic mechanisms without further increase in urinary Ca excretion. PMID- 3098951 TI - Long-term complications in a premature infant with tracheoesophageal fistula. AB - This is a report of the short- and long-term complications in a premature infant with tracheoesophageal fistula, including those related to central venous alimentation, seizures, chylothorax, bronchopulmonary dysplasia, dental erosions, gastroesophageal reflux, pulmonary problems, and gall stones. It offers analyses of possible alternate methods and treatments, which may have provided a better course. PMID- 3098952 TI - Evaluation of anticancer drugs by lymphocyte electrophoresis. AB - The spleen cells in tumor-bearing and normal mice treated with Krestin (PSK), mitomycin C (MMC) or adriamycin (ADM) were analyzed by cell electrophoresis and flow microcytometry. In normal mice, the splenocyte electrophoretic mobility histogram was observed as a bimodal pattern, and low and high mobility cells (LMC and HMC) corresponded with B and T cells, respectively. In sarcoma-180-bearing mice, an intermediate mobility peak (IMC) appeared between the low and high peaks. Although every anticancer drug depressed the IMC when the tumor was cured, MMC reduced the absolute number of splenic Ig+ and Thy-1+ cells, and ADM injured Ig+ cells in normal as well as in tumor-bearing mice. PSK, however, depressed splenomegaly by tumor-burden in spite of a slight increase in splenocytes of normal mice. In a previous paper, it was reported that the thymocyte mobility histogram was restored to a normal pattern by treatment with PSK in tumor bearers, while it was made more abnormal by treatment with MMC because of injury to cortical thymocytes. From these results, it may be considered that an anticancer drug which restored the splenocyte mobility histogram to a normal pattern without damages to thymocytes is preferable for cancer therapy. PMID- 3098953 TI - Effect of mitomycin C on the activation of adenylate cyclase in rat ascites hepatoma AH130 cells. AB - Isoproterenol (IPN)-stimulated activity of adenylate cyclase was enhanced in a dose-dependent manner by exposure of AH130 cells to mitomycin C (MMC). The enhancement was also observed in prostaglandin E1-, guanine nucleotide analog-, NaF-, cholera toxin- and forskolin-stimulated activities of the enzyme but not in manganese-stimulated activity. In addition, even when the cells pretreated with islet-activating protein were exposed to MMC, IPN-stimulated activity of adenylate cyclase was enhanced. Anaerobic exposure of AH130 cells to MMC somewhat inhibited IPN-stimulated activity of adenylate cyclase in contrast with aerobic exposure. Exposure of cells to adriamycin also caused enhancement of IPN stimulated activity of adenylate cyclase but exposure to nitrogen mustard inhibited the enzyme stimulation by IPN. The enhancing effect of MMC was lost by the combined treatment with alpha-tocopherol. From these results, it was shown that MMC modulated the activity of adenylate cyclase, probably through alterations in membrane structure. PMID- 3098954 TI - An in vitro model for the exposure of lung alveolar epithelial cells to toxic gases. AB - An in vitro model of lung alveolar tissue was developed by growing rat lung epithelial cells of Type II origin on hydrated collagen gels and subsequently maintaining the cultures at an air/liquid interface. The cultures provide a system to expose lung cells directly to toxic aerosols, fumes and gases. Nitrogen dioxide (NO2) was used to test the responsiveness of the cultures to toxic gases. Exposure to NO2 resulted in cytotoxicity and morphological alterations similar to those found in vivo, but at lower doses. Cell viability was analyzed by trypan blue dye exclusion, clonal survival and 3H-lysine incorporation. Dose-response relationships were determined at NO2 concentrations from 0-6.0 ppm (one hr exposure, room temperature) using cell viability assays. Decreased cell viability also resulted from increasing the time of exposure to 6 ppm of NO2 for up to one hr. This lung cell test system provides a rapid and economical system for the short-term toxicological testing of toxic gases, fumes, and aerosols. PMID- 3098956 TI - Computerized model for evaluating the kinetics of in vitro release of valpromide from controlled-release tablets under nonsink conditions. AB - A general mathematical model was developed to describe a dissolution system for tablets that have undergone attrition and maintained their geometric shape as concentration changed, i.e., starting with sink and ending with nonsink conditions. A computer program, designed for the microcomputer, was used to test the goodness of fit of the experimental data to the theoretical data by the chi 2 test. This program is more significant than a previous published program that relates to the more specific kinetic analysis of multidispersed powders undergoing dissolution under sink conditions. Concentration data obtained after dissolution tests of valpromide (2-propylvaleramide) controlled-release tablets performed under changing concentration conditions were checked in the two computerized models, which showed a better fit to the general model. PMID- 3098955 TI - Percutaneous absorption of 7, 10 14C-benzo[a]pyrene and 7, 12 14C dimethylbenz[a]anthracene in mice. AB - The percutaneous penetration, tissue distribution and excretion of 14C-labeled benzo[a]pyrene (BP) and dimethylbenz[a]anthracene (DMBA) were studied in mice. Both BP and DMBA rapidly penetrated the skin and were excreted more in the feces than in the urine. The proportion of BP and DMBA absorbed was less with increasing applied dose due to apparent saturation of the uptake process. Uptake from the dorsal skin of the nose was similar to uptake from the dorsal nuchal skin. PMID- 3098957 TI - Biodegradable microspheres. IV: Factors affecting the distribution and degradation of polyacryl starch microparticles. AB - Polyacryl starch microparticles have been suggested as lysosomotropic drug carriers. In this paper we report the study of the distribution and elimination of polyacryl starch microparticles after intravenous administration in mice. The half-life of the particles in the circulation is short (less than 5 min) and they are efficiently taken up by the reticuloendothelial (RES) system, mainly in the liver (50-90%). The stability of the particles, as studied both in vitro (with serum and lysosome preparations) and in vivo (via the elimination from the liver), depends on two factors, the amount of initiator of the polymerization process (N,N,N',N'-tetramethylethylenediamine, TEMED) and the degree of derivatization of the starch. TEMED, used for the polymerization of the acryl groups forming the hydrocarbon chains, determines the number and the length of the cross-links between the starch molecules. The results indicate that large amounts of TEMED induce the formation of particles with many and short cross links, which are easily degraded and dissolved in serum and more rapidly eliminated from the liver. The stability in serum can be improved by coadministration of soluble starch. Prolonged treatment of the starch with acrylic acid glycidyl ester leads to a high degree of derivatization and, consequently, to less degradable particles remaining in the lysosomes of the RES. The extent of biodegradation of the polyacryl starch particles could be anticipated from in vitro degradation of the monomers (acryloylated starch) with amyloglucosidase. PMID- 3098958 TI - Multidimensional column-switching liquid chromatographic method for dissolution testing of enprostil soft elastic gelatin capsules. AB - Enprostil (methyl 7-[(1 R,2R,3R)-3-hydroxy-2-[(E)-(3R)-3-hydroxy-4- phenoxy-1 butenyl]-5-oxocyclopentyl]-4,5-heptadienoate), an E-type prostaglandin exhibiting anti-ulcer activity, is formulated as a propylene carbonate solution filled into soft elastic gelatin (SEG) capsules. Enprostil SEG capsules were maintained for timed intervals at 50 degrees C, 30 degrees C, and room temperature, and the quantity of drug released upon complete capsule dissolution was determined as a function of storage condition. The dissolution test adhered to USP XXI guidelines (paddle method) and used a multidimensional HPLC technique to provide a sensitive and selective enprostil assay. Parallel HPLC assays determined the enprostil concentration in the propylene carbonate fill that was physically expressed from initially manufactured and from aged capsules. This corrected for any enprostil loss via chemical degradation on storage. The study included six different aged samples (six replicates each), and for all six samples, the enprostil recovered from dissolved capsules averaged 104 +/- 1.4% of the enprostil physically expressed from the capsules. Similarly, the enprostil recovered from dissolved, aged capsules averaged 103 +/- 5% of the enprostil physically expressed from capsules at the initial time point. These findings exclude the possibility that interactions with the SEG capsule wall reduce drug availability during storage under normal conditions. The multidimensional HPLC technique should generally extend to analysis of other noncationic drugs formulated into soft gelatin capsules. PMID- 3098959 TI - Alcohol effects on luteinizing hormone-releasing hormone stimulated luteinizing hormone and follicle-stimulating hormone in ovariectomized female rhesus monkeys. AB - The effects of acute alcohol administration on anterior pituitary function were studied in five ovariectomized female rhesus monkeys. Integrated plasma samples were collected for 80 min before and 120 min after nasogastric intubation of alcohol (2.5 or 3.5 g/kg) or isocaloric sucrose control solution. Then synthetic luteinizing hormone-releasing hormone (LHRH; 100 micrograms/i.v.) was administered and plasma samples were collected for an additional 180 min. After sucrose control administration, LHRH stimulated a significant increase in luteinizing hormone (LH) within 30 min (P less than .001) and follicle stimulating hormone (FSH) within 60 min (P less than .01). After alcohol administration, LHRH stimulated LH and FSH also increased significantly (P less than .01) when blood alcohol levels averaged 242 (+/- 26) and 296 (+/- 20) mg/dl. Moreover, there was an alcohol dose-dependent increase in LHRH-stimulated LH (P less than .01, .001) in comparison to control conditions, even though prealcohol and presucrose LH levels were equivalent. LHRH-stimulated FSH was also higher after 3.5 g/kg of alcohol than after 2.5 g/kg of alcohol and sucrose control administration (P less than .001) but base-line FSH levels before 3.5 g/kg of alcohol were also higher than control (P less than .05) or 2.5 g/kg of alcohol (P less than .001). An alcohol related enhancement of LHRH-stimulated LH without concomitant suppression of FSH in ovariectomized females contrasts with data reported previously in normally cycling females studied under identical conditions. The absence of ovarian steroid and/or ovarian peptide negative feedback in ovariectomized females may have permitted the synergistic effect of alcohol and LHRH on LH. PMID- 3098960 TI - Cardiac output is an apparent determinant of nitroglycerin pharmacokinetics in rats. AB - The steady-state pharmacokinetics of nitroglycerin (NTG) were investigated in 11 rats after sequential infusions of either NTG alone (10 micrograms/kg/min) or NTG plus vasopressin (the latter at 5.5 mU/kg/min). Arterial and venous plasma concentrations of NTG in the femoral bed were obtained at 41 and 45 min during each infusion phase. Cardiac output was estimated twice in each animal using 85Sr and 141Ce microspheres. NTG systemic clearance in arterial plasma was found to be strongly correlated with cardiac output (r = 0.784, n = 22, P less than .001). Because NTG distribution between red blood cells and plasma was independent of concentration (up to 150 ng/ml in plasma) and hematocrit (25-48%), the systemic clearance of NTG in arterial blood could be estimated as about 3/4 of cardiac output. Vasopressin co-infusion decreased both the cardiac output and the arterial NTG plasma clearance, but it also increased the arteriovenous extraction of NTG. Thus, vasopressin had not net effect on the venous plasma clearance, of NTG. In animals with NTG infusions alone, cardiac output also significantly correlated with NTG venous plasma clearance (P less than .01) and arteriovenous extraction (P less than .05). These data indicate that, in the absence of vasopressin, NTG pharmacokinetics are dependent on the cardiac output, thus providing an example wherein the systemic clearance of a drug was shown to be related to systemic blood flow. These results support the concept that the vasculature acts as a clearing organ for organic nitrates, and they also provide a hemodynamic explanation for the high variability in NTG plasma concentrations observed under presumed steady-state conditions. PMID- 3098961 TI - Pharmacologic characterization of acute chlordiazepoxide dependence in the rat. AB - A single intoxicating dose of chlordiazepoxide HCl (p.o.) in the rat can induce quantifiable manifestations of physical dependence. Dependence was revealed by antagonist precipitation (Ro 15-1788, CGS-8216) as well as spontaneous emergence of neurobehavioral signs of withdrawal observed by multiple raters blind to treatments. Ro 15-1788 was 45% more effective than CGS-8216 in both reversing chlordiazepoxide intoxication and expressing withdrawal signs. The severity of Ro 15-1788-precipitated withdrawal varied with chlordiazepoxide dose, Ro 15-1788 dose and the agonist-antagonist dose interval. Maximal precipitated dependence was evoked 3 days after chlordiazepoxide HCl (450 mg/kg) by Ro 15-1788 (25 mg/kg i.p.). The precipitated syndrome consisted of tail erection, reduced motor activity, high step, curled claw, arched back, muscle hypertonus and piloerection. Ro 15-1788-precipitated dependence emerged between 28 and 52 hr, peaked at 76 hr and disappeared by 124 hr. Spontaneous withdrawal had emerged from 100 to 124 hr and then faded gradually. The neurobehavioral expression of central nervous system depression and its reversal were necessary but not sufficient conditions for the induction and expression of acute chlordiazepoxide dependence. These results suggest caution in reviving acute benzodiazepine overdosed patients to avoid iatrogenic withdrawal analogous to naloxone for opiates. PMID- 3098962 TI - Lead, zinc and copper decorporation during calcium disodium ethylenediamine tetraacetate treatment of lead-poisoned children. AB - Asymptomatic Pb poisoning of children remains a serious public health problem in the United States. Ca disodium EDTA is often used therapeutically to reduce the body burden of Pb. Although this chelating agent promotes increased urinary excretion of Pb and lowers blood Pb concentration, it is a nonspecific metal chelator and it promotes a substantial increase in the urinary loss of the essential metal, Zn. In the work described here, the pattern and extent of changes in blood Pb and plasma Zn and Cu concentrations and of the urinary loss of these metals have been characterized in Pb-poisoned children receiving 5-day courses of 1000 mg of Ca disodium EDTA per m2 of surface area per day, given i.m. Both blood Pb and plasma Zn concentrations were reduced rapidly during treatment; plasma Cu concentration was unaffected. At 60 hr after the cessation of Ca disodium EDTA treatment, plasma Zn concentration rebounded rapidly to its pretreatment value but blood Pb concentration remained at about 60% of its pretreatment value. Treatment with Ca disodium EDTA produced an approximate 21 fold increase in the daily rate of urinary loss of Pb and about a 17-fold increase in the daily rate of Zn loss in urine. There was no increase in urinary loss of Cu above the endogenous level. The chelatable body burden of Pb was estimated by two related methods. Statistically significant correlations were found between chelatable Pb burdens estimated by either method and blood Pb concentrations before Ca disodium EDTA treatment. In contrast, no correlation was found between plasma Zn concentration and the urinary loss of Zn during chelation therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3098963 TI - A phorbol ester has dual actions on the mechanical response in the rabbit mesenteric and porcine coronary arteries. AB - To clarify the role of protein kinase C in the mechanical response, the effects of 12-o-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, were investigated on intact and skinned smooth muscle preparations of the rabbit mesenteric artery. TPA (0.1 microM) showed dual actions (initial enhancement followed by inhibition during long exposure) on the K+-induced contraction. The enhancement was marked in the presence of 39 mM-K+ but inhibition was the predominant effect in the presence of 128 mM-K+. Addition of 2.6 mM-Ca2+ to a Ca2+-free solution containing 2 mM-EGTA following application of A23187 (1 microM), produced contraction. TPA showed the same dual actions on this Ca2+ induced contraction. In chemically skinned muscles, TPA increased the amplitude of Ca2+-induced contractions evoked by low concentrations of Ca2+ (0.1-0.3 microM), but reduced those evoked by high concentrations of Ca2+ (1-10 microM). Both actions of TPA were facilitated in the presence of phosphatidylserine (PS). TPA with PS had no effect on the Ca2+-independent contraction evoked in relaxing solution containing 10 mM-EGTA and 4 mM-Mg ATP following application of adenosine 5-o-3-thiotriphosphate (ATP gamma S) and 0.3 microM-Ca2+. The amount of Ca2+ stored in cells estimated from the amplitude of the caffeine-induced contraction was not modified by application of TPA with PS in skinned or intact muscle tissues. The effects of TPA were investigated on the Ca2+ transient measured from the intensity of fluorescence of quin-2 in dispersed cell suspensions prepared from the porcine coronary artery. TPA had no effect on the Ca2+ transient in high K+ but enhanced the amplitude of the contraction. Amplitudes of the tonic response evoked by 39 mM-K+ in intact muscle tissues and the contraction induced by 0.3 microM-Ca2+ in skinned muscle were much the same. TPA with PS enhanced the amplitudes of both contractions to the same extent. From the above results, we concluded that TPA shows dual actions on the contractile machinery and may act on the regulatory systems of contractile proteins. Both excitatory and inhibitory actions of TPA depended on the concentration of Ca2+. However, the physiological action of protein kinase C as estimated from the action of TPA seems to be related to an excitatory action on the contractile machinery. PMID- 3098964 TI - Inorganic phosphate regulates the contraction-relaxation cycle in skinned muscles of the rabbit mesenteric artery. AB - The effects were investigated of inorganic phosphate (Pi) on the Ca2+-dependent and Ca2+-independent contractions evoked in chemically skinned smooth muscles of the rabbit mesenteric artery. The relation between the concentration of Ca2+ and tension showed a sigmoidal curve in the range of pCa 7-5.5. Pi (over 1 mM) inhibited the Ca2+-induced contraction, shifted the pCa-tension curve to the right and increased the Hill number from 2 to 3. Calmodulin did not change the Hill number and attenuated the inhibitory action of Pi as estimated from the shift of the curve, but this agent did not modify the increased Hill number in the presence of Pi. Pi consistently inhibited the Ca2+-independent contractions provoked by application of trypsin-treated myosin light chain kinase, of MgATP following adenosine-5'-o-(3-thiotriphosphate) (ATP gamma S) and Ca2+, and of a solution containing high Mg2+. These inhibitory actions of Pi were inversely proportional to the amplitude of the contraction. When Pi was applied simultaneously with ATP gamma S and Ca2+, there was no change in the amplitude of Ca2+-independent contractions provoked by the application of MgATP. The amplitude of the rigor contraction evoked by ATP-free solution was less than 7% of that of the 10 microM-Ca2+-induced contraction. When ATP was removed from the solution during the Ca2+ contraction, the rigor contraction was also generated. Pi did not inhibit either type of contraction. With a decrease in the concentration of Ca2+ from 10 microM to below 1 nM, the tissue relaxed at a slower rate than the rate of rise of the Ca2+-induced contraction. The slow relaxation was not modified by a change in the concentration of EGTA or addition of 1 microM-calmodulin. Pi reduced, and high Mg2+ prolonged the time required for the relaxation. This action of Pi was not prevented in the presence of calmodulin or of high Mg2+. The rates of rise and fall of the Ca2+-induced contraction depended on the concentration of MgATP, and Pi consistently inhibited the Ca2+-induced contraction in the presence of any given concentration of MgATP. We conclude that Pi may accelerate the detachment of cross-bridges between the contractile proteins. Thus, the amplitude of Ca2+-induced contraction is slightly inhibited and the relaxation is markedly facilitated. However, the site of action of Pi may differ from that of MgATP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3098965 TI - Thyroid hormone effects on lactase expression by rat enterocytes. AB - Thyroxine (T4) and triiodothyronine (T3) injected into adult rats causes first an increase and then a decrease in lactase activity measured subsequently in intestinal homogenates of rat jejunum. These changes are not associated with any alteration in intestinal structure or enterocyte migration rate. Quantitative cytochemistry shows T4 stimulation and inhibition of lactase activity to take place in upper villus and crypt cells respectively (O- and C-enterocytes). T3 injected into thyroidectomized rats produces identical stimulatory effects on lactase development to T4 injected into control animals. Radioactive T3 is distributed in all cell types following intraperitoneal injection into thyroidectomized rats. Highest amounts of recovered T3 are found in C- rather than O- enterocytes. Quantitative autoradiography shows intracellular T3 to be located in nuclear and cytoplasmic compartments following intraperitoneal injection. Simultaneous injection of non-radioactive hormone displaces 50-75% of radioactive T3. These results are discussed in relation to what is already known concerning the ability of thyroid hormones to affect intestinal development. The future need to study the physiological effects of T3 at the cellular level in the intestine is also emphasized. PMID- 3098966 TI - Patterns of breathing in response to alternating patterns of alveolar carbon dioxide pressures in man. AB - The time profile of alveolar PCO2 within the respiratory cycle has been forced to follow contrasting patterns in alternate breaths, in two different ways. Within breath changes (w.b.c., with a CO2-rich inspirate supplied early or late in alternate inspirations) involved minimal alternation of end-tidal PCO2. Between breath changes (b.b.c., with whole inspirates of CO2-free or CO2-rich gas) involved large swings of end-tidal PCO2. As previously reported (Metias, Cunningham, Howson, Petersen & Wolff, 1981), both patterns of forcing were associated with alternation of ventilation, but only when hypoxia was present. The patterns of the alternating reflex responses in 118 runs on four human subjects in steady hypoxia are described in terms of alternation of inspiratory and expiratory tidal volume, time and mean flow. These patterns often disappeared, or changed unpredictably in mid-run. The inspiratory pattern of reflex alternation depended in part on the type of forcing, but alternation of inspiratory tidal volume was usually observed with both types. No single pattern of expiratory alternation emerged as predominant. The pattern of reflex expiratory alternation was surprisingly independent of the pattern of inspiratory alternation: indeed, in w.b.c., but not in b.b.c., alternation of mean expiratory flow and of mean inspiratory flow were mutually exclusive. It is concluded that in man, as in cats and dogs, the arterial chemoreceptor pathway has access to various parts of the respiratory pattern generator, the exact response depending to some extent on the timing within the respiratory cycle. In particular, expiratory variables may be influenced directly through the arterial chemoreceptor pathway, i.e. without any supposedly mediating inspiratory alternation being demonstrable. The results are discussed briefly in relation to some current views on the organization of respiratory control. PMID- 3098967 TI - Plasma expansion does not precipitate the fall in plasma vasopressin in humans drinking isotonic fluids. AB - In a group of healthy humans, plasma vasopressin (AVP) levels fell on drinking either Tyrode or mannitol solutions isosmotic with plasma. Both the timing and magnitude of the fall were appropriate to account for the transient diuresis which followed the drinking. Although plasma expansion follows drinking Tyrode solution it occurred too late to account for the fall in plasma AVP. It was also too small to inhibit AVP secretion. Even though plasma volume tended to contract on drinking isosmotic mannitol solution a fall in plasma AVP and a diuresis occurred, similar to those found after drinking Tyrode solution. These findings appear to eliminate plasma volume expansion as the stimulus for the fall in plasma AVP and the associated diuresis on drinking isotonic fluids. In a further group of human subjects, bypassing the oropharynx by intragastric infusion resulted in a slower onset of diuresis after a water load. We suggest that receptors, as yet undefined, in the upper gastrointestinal tract contribute to the early stages of a water diuresis and account for the apparently inappropriate transient diuresis which follows the drinking of isotonic fluids. PMID- 3098968 TI - The pattern of sympathetic neurone activity during expiration in the cat. AB - The properties of sympathetic preganglionic neurone activity during expiration were studied in pentobarbitone-anaesthetized (n = 26) and in non-anaesthetized, mid-collicular decerebrate (n = 5), paralysed, artificially ventilated cats in which the electrical activity of the phrenic nerve and of the cervical sympathetic trunk was recorded. In control conditions (end-tidal PCO2 between 35 and 40 mmHg, zero end-expiratory pressure) sympathetic activity during expiration was either steady at a low level (n = 11) or showed a modest progressive increase from a low level in early expiration (n = 17). Very infrequently (n = 3), it showed a transient increase during the second half of expiration. Artificial ventilation with positive end-expiratory pressures in the range from 2.1 +/- 0.4 (mean +/- S.D.) to 6.7 +/- 0.6 cmH2O caused, in cats with intact vagus nerves, an increase in sympathetic neurone activity during the second half of expiration. Within this range of pressures, the magnitude of the increase was related to the magnitude of the positive end-expiratory pressure. This effect reversed at higher positive end-expiratory pressures. Pressures in excess of 10.2 +/- 1.8 cmH2O caused inhibition of sympathetic activity. The sympatho-excitatory effect of positive end-expiratory pressure disappeared after bilateral cervical vagotomy. With intact vagus nerves, it also disappeared at levels of systemic hypocapnia (end-tidal PCO2 less than or equal to 15 mmHg) which abolished phrenic nerve activity. In hypocapnia, artificial ventilation with peak tracheal pressures greater than 7.2 +/- 1.1 cmH2O caused inhibition of sympathetic activity, while ventilation with lower end-expiratory pressures had no effect on sympathetic activity. It may be concluded that the sympatho-excitatory effect of positive end expiratory pressure is mediated by vagal afferents and requires a certain level of brain-stem respiratory neurone activity. Sympatho-excitation during expiration was also observed, in normocapnic conditions, during short-duration static lung inflation with tracheal pressures in the range from 2.5 +/- 0.3 to 7.0 +/- 0.8 cmH2O as well as during artificial ventilation with zero end-expiratory pressure when lung inflation occurred in expiration. These responses were abolished by bilateral cervical vagotomy and during systemic hypocapnia. Sympatho-excitation during expiration was also observed when systemic hypercapnia was produced in vagotomized cats by artificial ventilation with gas mixtures containing 5 or 10% CO2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3098969 TI - In vitro cultivation of the vascular phase of Sarcocystis capracanis and Sarcocystis tenella. AB - Sporozoites of Sarcocystis capracanis and S. tenella (Apicomplexa) penetrated all four cell types tested (bovine monocytes, BM; bovine pulmonary artery endothelial cells, CPA; Madin-Darby bovine kidney; and ovine monocytes). Sporozoites of S. tenella developed to meronts in BM and CPA; those of S. capracanis developed to meronts in BM only. Both species of Sarcocystis developed to large first generation meronts followed by small meronts. At 40 to 50 days after inoculation (DAI) of sporozoites, considerably more merozoites of S. tenella were harvested from CPA (24.9 X 10(6) merozoites/75-cm2 flask; n = 4) than from BM (1.9 X 10(6) merozoites/75-cm2 flask; n = 4). Merozoites of S. capracanis were most numerous in BM at 88 to 100 DAI during which time 2.1 X 10(6) merozoites/75-cm2 flask (n = 4) were harvested. PMID- 3098970 TI - Cytolytic activity of Naegleria fowleri cell-free extract. AB - The cytotoxic activity of a cell-free extract of Naegleria fowleri amebae on B103 rat nerve cells in culture was investigated. The cell-free extract was prepared by subjecting lysed amebae to centrifugation at 100,000 g for 1 h, precipitation of the supernatant fluid with 30-60% saturated ammonium sulfate, and desalting by group exclusion chromatography utilizing Sephadex G-25. The supernatant fluid recovered from this procedure was termed the soluble fraction. The Naegleria cytotoxic activity present in the soluble fraction was assayed by 51Cr released from labeled B103 cells. The Naegleria soluble fraction, when added to nerve cells, elicited blebs on the B103 target cell surface within 5 min after exposure to the fraction. Later, holes were observed in the B103 cell plasma membrane. These alterations were never observed on untreated B103 cells. Phospholipase A, phospholipase C, and protease activities were associated with the desalted ammonium sulfate-precipitable cytotoxic activity of N. fowleri cell-free lysate. The cytotoxic activity was impaired by ethylenediamine-tetraacetate (EDTA), phospholipase A inhibitor (Rosenthal's reagent), heating at 50 degrees C for 15 min, or incubation at pH 10 for 60 min. Repeated freeze-thawing and inhibitors of proteolytic enzymes had no effect on the cytotoxic activity. Small amounts of ethanol (5% v/v) enhanced cytotoxic activity of the fraction. Phospholipases A and C, as well as other as yet unidentified cytolytic factors may be responsible for producing 51Cr release from target cells by the soluble fraction of N. fowleri extracts. PMID- 3098972 TI - Trends in enteral nutrition in the surgical patient. PMID- 3098971 TI - Effects of DL-alpha-difluoromethylornithine on Leishmania donovani promastigotes. AB - Alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, has been demonstrated to be an effective agent against a variety of parasitic protozoa but not against Leishmania spp. In this report, we show that Leishmania donovani promastigotes in continuous culture are sensitive to the growth inhibitory and cytotoxic effects of DFMO. Incubation of the promastigotes with DFMO obliterates intracellular putrescine pools and depletes spermidine concentrations, which correlates with the onset of growth inhibition. The effects of DFMO on the growth and the intracellular polyamine pools can be reversed completely by the addition of 10 microM putrescine to the culture medium. These results suggest that the treatment of leishmaniasis may be amenable to chemotherapeutic manipulation by DFMO. PMID- 3098973 TI - [Imaging of ureteral and pelvic diverticuli. Apropos of 49 cases]. AB - A review of 49 cases of rare ureteral and pelvic diverticula enables certain clinical and radiologic conclusions to be drawn. Lesions were bifid ureters with blind branches (20 cases), single (8 cases) or multiple (10 cases) diverticula of ureter and pelvic diverticula (11 cases). As previously reported, ureteral diverticula produced few clinical signs whereas these were marked in pyelic lesions. Multiple diverticula are particularly difficult to detect, but diagnosis is the rule from radiologic appearances and is generally confirmed by results of therapy. Their pathogenesis is poorly understood, however, mainly due to lack of histologic data, but recent studies by Cochran suggest they are a particular from of ureteritis. The only debatable point is the frequent association of multiple diverticula with bladder tumor, described by Cochran and confirmed by the authors and unlikely to be the result of chance. Further studies are necessary to provide clarification. PMID- 3098974 TI - CO2 laser laparoscopy for endometriosis associated with infertility. AB - Medical, surgical and combined therapy have been used in the treatment of infertility associated with endometriosis. The CO2 laser offers the advantage of precise excisional surgery at the initial laparoscopy and potentially avoids further surgery and medication. In 115 women in whom initial or follow-up laparoscopy revealed the presence of endometriosis, the CO2 laser was used to excise or ablate the endometriotic lesions. Fifty-five (48%) of the patients became pregnant, with 12-44 months of follow-up. These 55 patients have had 61 pregnancies. Forty-two (69%) were term, 7 (11%) are ongoing, 11 (28%) aborted, and 1 (2%) was ectopic. Twenty-three (68%) of 34 patients with endometriosis as the only infertility factor had 28 pregnancies. Thirty-two (40%) of the 81 patients with endometriosis associated with other infertility factors produced 33 pregnancies. PMID- 3098976 TI - Two new species of Leptotrombidium (Acari: Actinedida: Trombiculidae), probable vectors of scrub typhus in Thailand. PMID- 3098975 TI - Evaluation of kidney function in dogs suffering from canine encephalitozoonosis by standard clinical pathological and radiopharmaceutical techniques. AB - Canine encephalitozoonosis can be responsible for a severe renal disease in dogs which may develop into progressive, irreversible kidney failure. Three pure-bred Boxer littermates with confirmed encephalitozoonosis were subjected to sequential clinical pathological tests and renal biopsies. The endogenous serum creatinine and urea levels showed an initial temporary reduction but later increased steadily. The phenolsulphonphthalein retention test confirmed this end-stage renal disease. Initial hyper-gamma globulinaemia showed a rapid decline. Urinalysis was an indicator of chronic renal disease and the kidney biopsies confirmed progressive irreversible kidney lesions. Evaluation of sequential tests are advocated for the setting of a prognosis. The radiopharmaceutical techniques employed proved to be sensitive indicators of renal dysfunction and a means of evaluating the function of the left and right kidney separately. PMID- 3098977 TI - Effect of measles-virus infection and interferon treatment on invasiveness of Shigella flexneri in HEp2-cell cultures. AB - The influence of measles-virus infection on the invasiveness of Shigella flexneri in HEp2-cell cultures was studied. Bacterial invasiveness was significantly enhanced in cell cultures incubated with virus before bacterial inoculation. This effect was a function of time after introduction of virus to the cell cultures and of the concentration of virus. The increase in bacterial invasiveness was observed before production of infectious virus particles and before a cytopathic effect was evident. A similar enhancement of invasiveness was demonstrated when cell cultures were pretreated with UV-inactivated measles virus. Pretreatment of cells with interferon did not influence invasiveness, although it reduced the effect of measles-virus infection. PMID- 3098978 TI - The evaluation of a phage-typing system for Listeria monocytogenes for use in epidemiological studies. AB - A typing system for strains of Listeria monocytogenes based on the lytic properties of 28 phages has been evaluated with a set of strains isolated in the UK and tested in a blind trial. The system was highly reproducible and discriminatory, and 64% of all the strains tested could be typed. PMID- 3098979 TI - Aspects of the epidemiology of human Listeria monocytogenes infections in Britain 1967-1984; the use of serotyping and phage typing. AB - Strains of Listeria monocytogenes from 475 cases of human listeriosis collected during 1967-1984, belonged to one of three serogroups (1/2, 3 or 4). They were phage typed with a set of 28 phages to investigate three aspects of the epidemiology of listeriosis. Three patients each had two episodes of listeriosis, 3 months to 2 years apart, with strains of the same serogroup and indistinguishable by phage typing. Ten episodes of possible cross-infection between pairs of neonates in the same hospital occurred; the first baby was ill at or within 1 day of birth, and the second baby became ill 8-12 days after contact with the first. In each pair the L. monocytogenes strains were of the same serogroup and indistinguishable by phage typing. In three clusters of cases there may have been a common source of infection. L. monocytogenes strains from 10 of 11 cases of listeriosis in the Carlisle area in Jul.-Dec. 1981 were of the same serogroup; nine strains were non-phage-typable. The second cluster involved four adults treated at one hospital and the third a pair of neonates who were ill shortly after birth. In each cluster, strains were of the same serogroup, and were indistinguishable by phage typing. These last two clusters occurred during a short period when an unusually high proportion of strains from all cases of human listeriosis in Britain were indistinguishable by phage typing from the cluster strains, suggesting the possibility of common source infection. PMID- 3098980 TI - A new and simple method for preparation of thin aminoplastic standards for x-ray microanalysis. PMID- 3098981 TI - Larval salivary gland secretion proteins in Drosophila structural analysis of the Sgs-5 gene. AB - The structure of the Drosophila melanogaster salivary gland secretion gene Sgs-5 has been determined by DNA sequence analysis of cloned genomic DNA. This developmentally and tissue-specific gene is a member of the third instar intermolt gene set and is under control of the insect molting hormone ecdysterone. RNA protection experiments show that the RNA coding region of Sgs-5 contains 769 nucleotides and is divided into three exons by two small introns. The protein-coding region appears to begin after a short untranslated RNA leader (33 nucleotides) and to result in a protein of 163 amino acids. The first 18 amino acids give the amino-terminal end the highly hydrophobic nature characteristic of a signal peptide. PMID- 3098982 TI - Genes and loops in 320,000 base-pairs of the Drosophila melanogaster chromosome. AB - We have mapped the DNA sequences bound to the nuclear scaffold along 320,000 base pairs of a genetically well-defined region of the Drosophila chromosome. We have found that the domains delimited by the scaffold attachment regions are heterogeneous in size (ranging from 26,000 to 112,000 base-pairs in this interval), and that the attachment sites are within unique sequences as judged by blot hybridization. We also found that looped domains contain up to five, or even eight, unrelated genes including, in some cases, more than one transcribed gene. The loop organization unravelled here in cultured cells does not correspond to the banding pattern seen in salivary gland polytene chromosomes. PMID- 3098983 TI - Preliminary X-ray crystallographic study of methanol dehydrogenase from Methylophilus methylotrophus. AB - Single crystals of methanol dehydrogenase from Methylophilus methylotrophus have been prepared by the macroseeding method. The crystals belong to the monoclinic space group C2, and have unit cell parameters a = 125.62 A, b = 63.83 A, c = 83.99 A, and beta = 93.24 degrees. There is one 62,000 Mr monomer in the asymmetric unit. The crystals diffract to beyond 2.0 A resolution. PMID- 3098984 TI - Crystallization and crystallographic data for new forms of thymidylate synthase from Lactobacillus casei. AB - Several new crystal forms of thymidylate synthase (5,10 methlenetetrahydrofolate:dUMP C-methyltransferase; EC 2.1.1.45) were obtained by controlled pH change. In the crystals the dimeric molecule has a 2-fold symmetry axis coinciding with crystallographic symmetry. The crystals scatter to at least 2.7 A resolution in the synchrotron X-ray beam and appear to be suitable for high resolution X-ray diffraction analysis. The crystals were successfully derivatized and preliminary results are reported for the covalent inhibitory ternary complex of thymidylate synthase, 5-fluoro-2'-deoxyuridylate and 5,10 methylenetetrahydrofolate. PMID- 3098985 TI - Activity of a phage-modified RNA polymerase at hybrid promoters. Effects of substituting thymine for hydroxymethyluracil in a phage SP01 middle promoter. AB - Transcription of bacteriophage SP01 middle promoters is specifically initiated by a complex of the Bacillus subtilis host's RNA polymerase core (E) with the SP01 gene 28 transcription-regulating protein, gp28. Normal SP01 DNA contains hydroxymethyluracil (hmUra) in place of thymine and E . gp28 preferentially transcribes hmUra-containing DNA. Hybrid DNA molecules containing an SP01 middle promoter, PM25 . 1, have been constructed in which one DNA strand contains T and the other hmUra. The major feature of these reciprocal hybrid promoters is that one has, predominantly, T substituted for hmUra in the central -35 recognition sequence in the transcribed strand, while the other has, predominantly, T substituted for hmUra in the -10 recognition sequence in the non-transcribed strand. Binding by the E . gp28 RNA polymerase and transcription of these hybrid promoters and of the normal, all-hmUra, promoter have been compared. Both hybrid promoters are weaker than the normal PM25 . 1 promoter, but the hybrid promoter with T substituted in the -10 sequence is the weakest of the set. The DNase I footprint of the normal PM25 . 1 promoter shows temperature-dependent protection of a relatively long stretch of DNA downstream from the transcriptional start site, correlating with a thermal transition of transcriptional activity of promoter complexes. The stronger of the hybrid promoters also undergoes this transition, but the weaker does not. We discuss these findings in terms of protein-DNA interactions determining specificity for a modified nucleotide at this promoter. PMID- 3098986 TI - Defining the lower limits of blood-brain barrier permeability: factors affecting the magnitude and interpretation of permeability-area products. AB - Experimental alteration in the restricted permeability of the blood-brain barrier to polar, blood-borne molecules is often quantitated in the rat with use of 14C sucrose or 3H-mannitol delivered as a test substance into the circulation. The underlying principle is to relate the quantity of saccharide that has permeated into brain parenchyma, after an arbitrary time period, to some index of the circulating tracer level. This study indicates that to correct the radioactivity level in the brain tissue for intravascular tracer, it is an erroneous practice to estimate the latter as the product of tissue blood volume and the tracer concentration measured in a systematic blood sample. Dissected brain tissue was found to have a lower hematocrit and thereby larger plasma/tracer compartment per unit blood volume than femoral arterial blood. It is further shown that, although commercially supplied stocks of 14C-sucrose or 3H-mannitol may contain only small quantities of radioactive impurities, their inclusion in injectates and preferential uptake into brain may cause significant overestimation of permeability to the parent tracer. It is also confirmed that magnitude of permeability-area (PA) products for permeation of purified sucrose or mannitol into brain varies inversely with the length of time allotted for tracer circulation in the bloodstream. This finding is at variance with the assumptions of a two-compartment (plasma/brain) diffusion model underlying such measurements and supports a recently published model for blood-to-brain transfer based on multiple uptake compartments in brain parenchyma. The factors compromising PA measurement identified in this study may partly underlie variations in PA values published from several laboratories that had been attributed to genetic differences in laboratory rats. PMID- 3098987 TI - Effect of a diet rich in branched chain amino acids on severely burned guinea pigs. AB - This study was performed to investigate the effects of dietary supplementation with branched-chain amino acids (BCAA) for postburn nutritional management. Seventy-one burned guinea pigs (30% TBSA) with previously placed catheter gastrostomies were divided into six groups. The first, second, and third groups received 10%, 20%, and 30%, respectively, of total calories as whey protein. The other three groups received BCAA supplementation to increase BCAA to 50% of total amino acids, compared to 21.5% BCAA content in whey protein. Groups I and IV received isonitrogenous intake, as did groups II and V, and III and VI, respectively. After an initial 3-day adaptation period, all animals in all groups received continuous isocaloric (175 kcal/kg/day) intragastric tube feeding until postburn day (PBD) 14. At PBD 14, although BCAA-supplemented groups showed very high plasma levels of BCAA (IV: 169%; V: 306%; VI: 770% of normal), no BCAA group showed evidence of any beneficial effect in various nutritional parameters when compared with the corresponding whey protein group with isonitrogenous intake. Cumulative nitrogen balance and mortality during 14 days were significantly worse in BCAA groups IV and VI than in control groups I and III, respectively. It is concluded that BCAA supplementation to enteral diets has no beneficial effect for postburn nutritional management following severe burn injury. It is further suggested that when nitrogen intake is too low or very high, BCAA supplementation may have an adverse effect. PMID- 3098988 TI - Circumstantial epidemiology of Schistosoma mansoni in the West-Nile district of Uganda: results of a cross-sectional study in the Rhino Camp area. AB - A cross-sectional survey of Schistosoma mansoni was undertaken at the Rhino Camp of the West-Nile district of Uganda to establish baseline data for subsequent studies intended to compare this area (a low transmission area) with Pakwach area (high transmission). An overall prevalence of 37% of S. mansoni infection was demonstrated. There was no statistically significant difference in prevalence between males and females. Six per cent of all cases were heavily infected (400 eggs g-1 of faeces). There was no statistically significant difference in prevalence between those with pit-latrines and those with no conventional method of excreta disposal. PMID- 3098989 TI - Predictive value of specific signs and symptoms for the diagnosis of acute Chagas' disease in children. PMID- 3098990 TI - Long-term suppression of luteinizing hormone, follicle-stimulating hormone and testosterone by daily administration of leuprolide. AB - The chronic effect of long-term injections of leuprolide on the hypothalamic, pituitary and gonadal axes have been studied in men with advanced prostatic cancer. The possibility of transient acute changes in luteinizing hormone, follicle-stimulating hormone and testosterone after each daily injection was studied in 31 patients treated for more than 1 year. No evidence of escape from daily 1.0 mg. doses was noted. No pituitary responsiveness was observed at any time point examined. Thus, daily administration of 1.0 mg. leuprolide acetate subcutaneously produces durable, complete suppression of gonadotropins and testosterone for prolonged periods. PMID- 3098991 TI - A cost-effectiveness analysis of prophylaxis against deep-vein thrombosis in major orthopedic surgery. AB - A number of methods of prophylaxis can reduce the likelihood of postoperative deep-vein thrombosis in patients undergoing major orthopedic surgery. Using techniques of decision analysis, we examine the cost-effectiveness of several of these--warfarin sodium, low-dose subcutaneous heparin sodium, graduated compression stockings, intermittent pneumatic compression, heparin plus dihydroergotamine mesylate, and heparin plus stockings--compared with clinical diagnosis and treatment only. Our results show that 153 deaths per 10 000 patients occur when no prophylaxis is used; with most prophylaxis, this number is at least halved, and the most effective methods may reduce the number of deaths by three fourths. In addition, all of the prophylaxis considered are cost saving: average costs of care (including prophylaxis costs) are reduced by +19.40 to +181.60 per patient. Prophylaxis against deep-vein thrombosis in major orthopedic surgery therefore saves both lives and health care dollars. PMID- 3098992 TI - Decrease in plasma high-density lipoprotein cholesterol levels at puberty in boys with delayed adolescence. Correlation with plasma testosterone levels. AB - A three-phase study tested the hypothesis that the decrease in the high-density lipoprotein cholesterol (HDL-C) level observed in boys at puberty is related to an increase in the plasma testosterone concentration. In phase I, 57 boys aged 10 to 17 years were categorized into four pubertal stages based on clinical parameters and plasma testosterone levels. These four groups showed increasing plasma testosterone values and decreasing HDL-C levels. In phase II, 14 boys with delayed adolescence were treated with testosterone enanthate (100, 200, and 200 mg/mo, respectively, for three months). Plasma testosterone levels during therapy were in the adult male range. Levels of HDL-C decreased by a mean of 7.4 mg/dL (0.20 mmol/L) and 13.7 mg/dL (0.35 mmol/L), respectively, after the first two doses. In phase III, 13 boys with delayed adolescence demonstrated increasing plasma testosterone levels and decreasing HDL-C levels (-12.0 mg/dL [-0.30 mmol/L]) during spontaneous puberty. Levels of HDL-C and apolipoprotein A-1 were correlated during induced and spontaneous puberty. Testosterone should be considered a significant determinant (not necessarily directly causal) of plasma HDL-C levels during pubertal development. PMID- 3098993 TI - End-tidal carbon dioxide monitoring during cardiopulmonary resuscitation. AB - The end-tidal carbon dioxide (CO2) concentration has been found to correlate with cardiac output during and after cardiopulmonary resuscitation (CPR) in animal models. We monitored end-tidal CO2 values continuously during cardiac resuscitation in 23 humans while ventilation was held constant with a computer controlled CPR Thumper. This report focuses on ten of the 23 patients who experienced return of spontaneous circulation (ROSC) during monitoring. There was no significant difference in the end-tidal CO2 value of patients without ROSC (1.8% +/- 0.9%) and the end-tidal CO2 value of patients before ROSC in patients who had ROSC (1.7% +/- 0.6%). The end-tidal CO2 concentration increased immediately in all patients who had ROSC, from 1.7% +/- 0.6% to 4.6% +/- 1.4%, then gradually returned to a new baseline (3.1% +/- 0.9%). Change in the end tidal CO2 value was often the first clinical indicator that ROSC had occurred. Our findings suggest that end-tidal CO2 monitoring may provide clinically useful information that can be used to guide therapy during CPR. PMID- 3098994 TI - Cardiogenic shock due to antihistamine overdose. Reversal with intra-aortic balloon counterpulsation. PMID- 3098995 TI - Report on the 1986 A.S.P.E.N. Research Workshop on selenium in clinical nutrition. AB - Selenium in human nutrition was the theme of the 1986 Research Workshop of the American Society for Parenteral and Enteral Nutrition. At the workshop, evidence for the nutritional essentiality of selenium to humans was reviewed, and it was concluded that Keshan disease, the cardiomyopathy of children and young women described in China, is now firmly linked to selenium deficiency, although other factors may be involved. Selenium metabolism and techniques for assessing selenium status also received attention at the workshop. A measurement of blood selenium levels was accepted, in general, as a valid technique for assessing selenium status in individuals with relatively constant selenium intakes. Clinical practitioners at the workshop reported that some of their total parenteral nutrition patients not receiving selenium presented biochemical evidence of selenium deficiency, but no characteristic clinical syndrome due to selenium deficiency has yet been observed in such patients. The workshop attendees acknowledged the need for an official guideline for selenium use in total parenteral nutrition, but were unable to develop a consensus regarding such a guideline. However, the workshop agreed that any guideline established in the future should specify the type of patients to be supplemented, the dose of selenium to be administered, and the selenium compound to be used. Until that time, the physician supervising the therapy must assume responsibility both for determining the need for selenium supplementation, and for the administration of the supplemental selenium. PMID- 3098996 TI - Impaired wound healing in surgical patients with varying degrees of malnutrition. AB - The relationship between nutritional state and wound healing was examined in 66 adult surgical patients. Wound-healing response was assessed by measuring the collagen content (hydroxyproline) of fine tubes of Gore-tex inserted subcutaneously along standardized needle track arm wounds. After a period of 7 days, the tubes were removed and it was found that there was a higher hydroxyproline content in the tubing of 36 normally nourished patients than there was in the tubing of 21 patients with mild protein energy malnutrition (p less than 0.01) and 9 patients with moderate to severe protein energy malnutrition (p less than 0.01). There was no difference in the wound-healing response between the two latter groups of patients who had significantly different degrees of malnutrition. The results suggest that a definite abnormality in the wound healing response exists in malnourished surgical patients, but it occurs earlier in the course of the illness than previously supposed. PMID- 3098997 TI - Effects of resistive exercise on skeletal muscle in marrow transplant recipients receiving total parenteral nutrition. AB - Skeletal muscle protein loss occurs during marrow transplantation despite total parenteral nutrition. To determine if muscle atrophy could be minimized with exercise therapy, 30 patients undergoing marrow transplantation for acute leukemia completed a prospective randomized trial to receive: (1) no therapy (controls), (2) physical therapy thrice weekly (PT3), or (3) physical therapy five times weekly (PT5). Patients were studied through 35 days posttransplant. Muscle protein status and turnover was assessed by weekly nitrogen balance, and creatinine and 3-methylhistidine excretion. Results favored a muscle protein sparing effect of exercise, as a significant decrease in creatinine excretion in controls only suggested muscle protein loss associated with inactivity. Changes in arm muscle area correlated with energy, but not protein intake. Large individual variation, inadequate nutritional support and differences in admission arm muscle area may have clouded these results. PMID- 3098998 TI - The effect of protein malnutrition and nutritional support on the mechanical properties of fracture healing in the injured rat. AB - We investigated the effect of different nutritional regimens on fracture healing in the injured rat model. Four groups, each consisting of 12 male rats (307 +/- 16 g), were subjected to anesthesia, laparotomy (injury), and tibial osteotomy with internal fixation. Group I received 23% protein, group II received 23% protein and high caloric feed, group III received 5% protein, and group IV received 38% protein. After 8 weeks, calluses were x-rayed and the tibia was removed, fixed in a special block of methyl-metacrylate, and tested at tension up to failure in a mechanical testing apparatus. The distraction force at failure was measured, and callus stiffness and energy absorbed to failure were calculated. The low protein diet resulted in significantly lower tensile strength and stiffness of calluses compared to the other three dietary regimens, this despite adequate caloric intake. In addition, the low protein diet resulted in a callus with "rubbery" mechanical properties compared to the "rigid" calluses of the other three groups. The high protein diet did not result in any significant improvement in fracture healing. These results gain clinical significance in the face of a high incidence of protein calorie malnutrition in injured orthopedic surgery patients. PMID- 3098999 TI - Endoscopic, radiographic, and clinical response to prolonged bowel rest and home parenteral nutrition in Crohn's disease. AB - Total parenteral nutrition is widely used as a therapeutic measure in patients with severe, active Crohn's disease unresponsive to conventional medical management. We have reviewed our experience with 10 patients with nonfistulous Crohn's disease treated by home parenteral nutrition (HPN) and bowel rest (nothing-by-mouth) assessing the nutritional, radiologic, endoscopic, and clinical responses. After a mean of 4.1 months of treatment, all patients had a marked improvement in nutritional status and resolution of gastrointestinal symptoms; 90% reduced their corticosteroid dose. Eight of nine patients had endoscopic and/or radiographic evidence of mucosal healing. Although 60% of patients were able to avoid surgery and tolerate refeeding, all six patients continue to require steroids to control symptoms. Our study suggests that HPN and bowel rest is a useful therapeutic approach to selected patients with active Crohn's disease, which permits a reduction in corticosteroid dosage and partial healing of mucosal lesions in most. Further studies are required to determine which patients should receive HPN and its optimal duration. PMID- 3099000 TI - Postoperative parenteral nutrition with high supply of branched-chain amino acids: effects on nitrogen balance and liver protein synthesis. AB - Branched-chain amino acids (BCAA) stimulate muscle and liver protein synthesis in vitro. The significance of this action in catabolic conditions in vivo remains controversial. The effects of a high supply of BCAA in total parenteral nutrition (TPN) on nitrogen balance and liver protein synthesis were studied in a postoperative rat model. After standard operative trauma TPN was commenced with one of two isocaloric programs (I: 20.1% BCAA and II: 50% BCAA) and continued for 48 hr. The relative rate of liver protein synthesis, measured after TPN in vitro by perfusion with 14C-leucine, was similar in both groups (I: 53.4 +/- 17.3 and II: 49.0 +/- 27.3 arbitrary units of synthesis rate, mean +/- SD). The cumulative nitrogen balance was positive with both regimens and was not improved by the high supply of BCAA (I: 2.02 +/- 0.81 and II: 1.87 +/- 0.63 gN/kg/48 hr mean +/- SD). We conclude that after moderate surgical trauma TPN with a high supply of BCAA offers no advantage over conventional TPN. PMID- 3099001 TI - Protein synthesis in skeletal muscle in relation to nitrogen balance after abdominal surgery: the effect of total parenteral nutrition. AB - Protein synthesis in skeletal muscle was studied in patients after elective abdominal surgery, using the concentration and size distribution of ribosomes. The patients were given either an electrolyte solution or total parenteral nutrition postoperatively. The analyses were performed on muscle biopsy specimens taken prior to surgery and on days 1 and 3 following surgery. The percentage content of polyribosomes, total ribosome concentration and the polyribosome concentrations per milligram of tissue DNA were determined. Elective abdominal surgery caused a significant decrease (p less than 0.05) in the three variables. Total parenteral nutrition did not prevent the decrease. The negative nitrogen balance was significantly improved by total parenteral nutrition, but it did not reach equilibrium. The results show that total parenteral nutrition given postoperatively did not maintain protein synthesis activity in skeletal muscle. The improvement in nitrogen balance suggests that amino acids are utilized by tissues other than skeletal muscle. PMID- 3099002 TI - Effect of enteral formula infusion rate, osmolality, and chemical composition upon clinical tolerance and carbohydrate absorption in normal subjects. AB - It is a common clinical practice to initiate enteral hyperalimentation using low flow rates or diluted formula. These adjustments are made in an effort to minimize patient intolerance. Using complex and elemental enteral formulas, we investigated whether various flow rates or osmolalities effected clinical intolerance or carbohydrate malabsorption in 20 healthy volunteers. Our infusion rates ranged between 50 and 150 kcal/hr and the osmolalities ranged between 325 and 690 mOsm/Kg of water. Even at the maximal flow rate and osmolality, our results show that both types of enteral formulas were well tolerated as assessed by the frequency of abdominal pain, bloating, passage of rectal gas and stooling. No carbohydrate malabsorption was detected as measured by breath hydrogen. In well nourished subjects, our findings do not support the common clinical practice of initiating alimentation with low flow rates or diluted formula. PMID- 3099003 TI - Aluminum in parenteral nutrition solution--sources and possible alternatives. AB - The extent of aluminum (Al) contamination in parenteral nutrition (PN) solutions for infants is not known. Aluminum was measured in 136 samples from various commercially available components that are used with PN. Results showed Al content varied widely among different components. The same chemical may have a different Al content depending on the manufacturer. However, Al contents were similar among lots from the same manufacturer for the same chemical. Aluminum contamination was arbitrarily classified as high (greater than 500 micrograms Al/liter), intermediate (51-500 micrograms Al/liter) or low (less than or equal to 50 micrograms Al/liter). The high group included most calcium and phosphorus containing salts, 1 multivitamin preparation, folic acid, ascorbic acid and concentrated (25%) albumin. The intermediate group included sodium lactate, potassium phosphates, zinc and chromium chloride, multitrace metal preparation, and 5% plasma protein. The low group included amino acids, sterile water and dextrose water, chloride salts of sodium, potassium, calcium, copper and chromium, sodium phosphates, magnesium sulphate, zinc sulphate, vitamin B12, vitamin K1, 1 multivitamin preparation, soybean oil emulsion and heparinized (2 U/ml) saline. PN solutions made from high Al components may contain up to 300 micrograms Al/liter. Calcium gluconate contributed greater than 80% of the total Al load from PN. Lowering of Al content in calcium gluconate in addition to use of specific low Al components offers the opportunity to significantly lower the Al concentration of the final PN solution and theoretically may achieve an Al content as low as 12 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099004 TI - Effects of infused intralipids on neutrophil chemotaxis during total parenteral nutrition. AB - A number of previous studies have suggested that the fat emulsion, Intralipid, might compromise human host defenses, due mainly to impairment of neutrophil functions. The aim of this study was to evaluate the effects of Intralipid on neutrophil chemotaxis in cancer patients receiving total parenteral nutrition including 500 ml of 20% Intralipid over 6 hours (83 ml/hr). No impairment of neutrophil chemotaxis was found during or after lipid infusion. Further investigations are necessary to determine whether, in routine clinical practice, intralipids are responsible for impairment of other neutrophil functions and whether side treatments have a protective effect for neutrophil functions. PMID- 3099005 TI - Influence of parenteral nutrition on phospholipid metabolism in posttraumatic rat lungs. AB - In the current investigation, we studied two groups of rats--one group supplied exogenous phospholipid precursors (carbohydrate plus fat emulsion group) and the other given only calories (carbohydrate group)--to evaluate the effects on surfactant composition by normocaloric alimentation, using a hypovolemic traumatic shock model. The total phospholipid (PHL) contents of lung tissue were similar in both groups. However, we found differences in the dipalmitoylphosphatidylcholine fraction (DPPC--the most important component of surfactant material) in both lung tissue and lavage fluid. With lipid emulsion, there was an increased fraction of saturated lecithins (mainly DPPC) both in lung tissue and lavage fluid, similar to former studies with hypocaloric alimentation. In this model, those findings suggest that the PHL pattern does not depend on the quantity of caloric supply, but, rather, on the infusion composition. The enhanced DPPC content is further reflected in improved surfactant status: lipid in parenteral nutrition (PN) may exert a direct salutary effect on lung mechanics. PMID- 3099006 TI - Alteration of lipoprotein profile during total parenteral nutrition with intralipid 10%. AB - Eight patients were studied for lipoprotein profiles over a period of 3-7 weeks. Four patients received total parenteral nutrition (TPN), including 1000 ml/day of Intralipid 10%. Three patients received fat-free TPN, and one patient was tube fed 1000 ml/day of Intralipid 10% enterally. Fat-free TPN lowered plasma lipid, especially low density lipoprotein (LDL) and high density lipoproteins (HDL). On the other hand, intravenous administration of Intralipid 10% caused a marked increase of LDL, together with increases of phospholipid and cholesterol, especially free cholesterol. Triglyceride, VLDL, and HDL remained within the normal range in this group. Enteral administration of the same amount of Intralipid 10% did not cause a rise of LDL. Lipid composition of the increased LDL approximated that of lipoprotein X with the intravenous Intralipid 10%. From these findings, we suggest that phospholipids in Intralipid 10% formed abnormal LDL as the result of mobilization of cholesterol from extravascular tissues, when administered intravenously. PMID- 3099007 TI - Impaired fat utilization in parenterally fed low-birth-weight infants suffering from sepsis. AB - Lipid infusion in low-birth-weight infants suffering from sepsis is still controversial. Consequently, we investigated the fat tolerance in six low-birth weight infants with sepsis and 15 low-birth-weight infants without sepsis. For measurement of fat clearance, we assayed the serum concentrations of triglycerides enzymatically, and of the free fatty acids by colorimetric micromethod. The fatty acid oxidation was analyzed with the [13C]triolein breath test by means of ratio-mass spectrometry. The infants were maintained on continuous parenteral nutrition with various amounts of soybean oil emulsion (1 g, 2 g, and 3 g fat/kg body weight per day). Comparing the lipid infusion of 1 and 2 g fat/kg body weight per day between the two groups, we found triglyceride and free fatty acid values in both groups to be in the normal range. At a dose of 3 g of fat/kg body weight per day, septic low-birth-weight infants showed a significantly higher concentration of triglycerides (2.02 +/- 0.46 mmol/liter) and of free fatty acids (2.06 +/- 0.45 mmol/liter) than the nonseptic low-birth weight infants (triglycerides: 1.09 +/- 0.43 mmol/liter; free fatty acids: 1.05 +/- 0.41 mmol/liter). The low-birth-weight infants with sepsis showed a reduced fat oxidation rate of 16.0 +/- 1.5% in contrast to that of the low-birth-weight infants without sepsis, whose rate was 38.4 +/- 1.8%. Accordingly, we apply dosages not exceeding 2 g of fat/kg body weight per day to septic low-birth weight infants. PMID- 3099008 TI - Plasma phospholipid fatty acids and urinary excretion of prostaglandins PGE1 and PGE2 in infants during total parenteral nutrition, with continuous or sequential administration of fat emulsion. AB - During total parenteral nutrition, using an identical supply of fat emulsion (350 mg/kg/24 hr) to correct essential fatty acid deficiency in children, the efficacy of two methods of administration was studied: continuous over 24 hr, or discontinuous 3 hr/day. At the beginning of the study, all the infants (1-4 months old) had proven essential fatty acid deficiency. After at least 1 month of one of the two nutritional protocols (continuous or discontinuous), plasma phospholipid fatty acid composition and PGE1 and PGE2 urinary excretion were measured. The results obtained indicate better utilization of the fat emulsion when it is administered almost every day, in continuous infusion over 24 hr (1 g/kg/24 hr of Intralipid 20%). PMID- 3099009 TI - Nutritional support team vs nonteam management of enteral nutritional support in a Veterans Administration Medical Center teaching hospital. AB - One hundred one patients receiving enteral nutritional support (ENS) by tube feeding during a 5-month period were prospectively studied. Fifty patients were managed by a nutritional support team (T) and 51 patients were managed by the nonteam approach (NT). Demographics, primary diagnosis, chronic diseases, medical service, calculated basal energy expenditure (BEE), duration of ENS, and final patient disposition were recorded. Enteral formula, formula modifications, results of laboratory tests and calories delivered were obtained daily. Results of nitrogen balance studies were obtained when available and each patient was monitored for pulmonary, mechanical, gastrointestinal, and metabolic abnormalities. No significant difference was found between the team and nonteam managed groups in regard to total feeding days, mean feeding days per patient, total laboratory tests, laboratory tests per patient or laboratory tests per day. Significantly more team patients attained 1.2 times BEE (T = 47, NT = 38, p less than 0.05) for a significantly greater period of time (T = 398 days, NT = 281 days, p less than 0.05). Significantly more team patients achieved a measured positive nitrogen balance than nonteam patients (T = 42, NT = 1, p less than 0.05). Formula modifications to correct nutritional or metabolic aberrations were made in 15 (30%) team patients and five (9.8%) nonteam patients (p less than 0.05). The number of individual abnormalities (pulmonary, mechanical, gastrointestinal, and metabolic), as well as total abnormalities occurring in the team-managed group, was significantly lower than in the nonteam managed group (160 vs 695, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099010 TI - Association of parenteral nutrition catheter sepsis with urinary tract infections. AB - The infection rate (IR) of central venous catheters (CVCs) used for parenteral nutrition (PN) was prospectively evaluated over a 12-month period, with emphasis on the relationship between CVC sepsis and preexisting sites of infection. Sepsis was presumed if the CVC tip or blood culture was positive, or if defervescence followed CVC removal. Four hundred seventy-three CVCs were placed for PN for a total of 5,422 patient days, with a mean length of stay of 11.5 days. Twenty two CVCs led to sepsis for an IR of 4.65% or 4.06 infections per 1000 patient days. Twenty of the 22 septic CVCs were in patients with other sites of infection. The IR was 12.0% (20/166) when other sites of infection were present and 0.65% (2/307) in the absence of a second site. The mean length of stay was 13.2 days for CVCs with other sites of infection and 10.3 days for CVCs with no other site of infection. Fifty nine percent of septic CVCs had secondary sites of infection that included urinary tract infections (UTI). Of all septic CVCs, 22.7% had no site of infection other than UTI. The presence of UTI appears to present a high risk of CVC sepsis. Appropriate identification and treatment of UTI prior to CVC insertion is recommended. PMID- 3099011 TI - Total parenteral nutrition catheter sepsis: impact of the team approach. AB - For a period of 32 months from the inception of the Parenteral and Enteral Nutrition (PEN) Team at the University of Michigan, the infection rate (IR) related to central venous catheters (CVCs) for total parenteral nutrition (TPN) was prospectively evaluated. Six hundred twenty-two catheters were placed in 377 patients for a total of 9,200 patient days. The length of CVC stay ranged from 2 to 108 days with a mean of 14.5. CVC longevity was longer on units where certification of nurses by the PEN team was mandatory (mean 20.4 days, IR 3.5%) vs comparable units which utilized informal instruction (mean 14.4 days, IR 3.5%). Twenty-two catheters led to patient sepsis for a rate of 3.5%, or 2.39 CVC related infections per 1000 patient days. The preteam infection rate was 24.0%, as determined by a 6-month prospective study. Infection rates for CVCs used for TPN only and those used for parenteral nutrition (PN) plus blood products, antibiotics, and CVP measurements were identical, 3.5%. The team approach can effectively increase PN catheter longevity and reduce infection rates. Conservative cost accounting of best and worst case scenarios determined a range of $3,700 to $8,900 per episode of catheter sepsis. PMID- 3099012 TI - A model for the prediction of osmolalities of modular formulas. AB - A model is proposed for evaluation of osmolality of multicomponent formulas composed of modular ingredients. Nonlinear curve-fitting techniques applied to empirical data result in prediction of the osmolality of ingredients for any concentration desired. Osmolality of a multicomponent formula can be obtained by adding osmolalities of ingredients. Data handling is made possible by the use of simple microcomputer programs. The model is tested with products available for construction of amino acid-restricted diets. PMID- 3099013 TI - Total nutrient admixture: a review. AB - The TNA system of nutritional support has become very popular and offers some unique advantages over the traditional method of administering TPN to hospitalized and home patients. However, these advantages as outlined in this review, must be carefully weighed against potential disadvantages before the TNA system is employed as a nutritional support modality. It should also be noted that the stability of TNA systems is not well established since many stability studies do not provide specific information regarding formulations tested. In addition, many studies do not utilize methods to determine the entire spectrum of particle size and distribution. Droplet size in TNA systems attain a diameter several times larger than the 0.2 to 0.4 micron of manufacturer's lipid emulsions and naturally occurring chylomicrons. Although the administration of the TNA system has not been associated with any acute toxicity, the long-term consequences of infusing droplets larger than 0.4 micron is not definitely known. In addition, the biological implications of using the TNA system need to be elucidated. Subtle differences in the properties of the lipid emulsion can affect the way it is metabolized by the body. Wretlind has mentioned that two apparently similar soybean oil emulsions, Intralipid, and Lipofundin are handled differently by the body. Minor differences in the phospholipid layer of the droplets were postulated as a cause. Certainly the nature of the emulsifying layer of phospholipid on TNA system droplets is modified and therefore may be metabolized differently. The recent report of enhanced growth of microorganisms in TNA systems is also worrisome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099014 TI - Use of an intercostal vein for central venous access in home parenteral nutrition: a case report. AB - A key factor in the success of a home parenteral nutrition program is prolonged and safe access to the central venous system. There are some patients, however, in whom the cephalic, external jugular, internal jugular, subclavian, and saphenous veins cannot be used. In these patients, cannulation of an intercostal vein can be useful for central venous access. Such a patient was recently presented to our medical care facility with bilateral subclavian vein thrombosis, left external iliac vein thrombosis, and superior vena cava obstruction above the level of the azygous vein. A Broviac catheter was successfully introduced via a right intercostal vein cutdown with the catheter tip lying in the azygous arch. This is the first known description in an adult patient in the use of an intercostal vein to gain access into the central venous system. PMID- 3099015 TI - Mild peripheral neuropathy but biochemical chromium sufficiency during 16 months of "chromium-free" total parenteral nutrition. AB - A 6-yr, 4-month-old boy was started on total parenteral nutrition (TPN) because of chronic diarrhea. The TPN regimen (3 liter/day) initially included supplemented Cr (3 micrograms/day) in addition to standard components (including FreAmine III). At age 8 yr, 8 months, the serum Cr level was elevated: 3.7 ng/ml (normal 0.03-0.85). A repeat level at the same time by another commercial laboratory was also high (7.0). Cr supplementation was stopped. At age 10 yr, he was noted to have mild peripheral neuropathy although glucose tolerance was excellent (alpha-linolenic acid was undetectable in the plasma). Cr status was reevaluated in a research lab. The serum level was 1.4 ng/ml (normal 0.05-0.4). The urine chromium excretion was 1.27 micrograms/day (normal 0.22). The TPN regimen (unsupplemented with Cr) provided 4 micrograms/day. Normal Cr intake is about 60 micrograms/day with 0.4% absorption (net 0.24 microgram/day). We conclude that Cr contamination of standard PN fluid may prevent biochemical evidence of low Cr status. In addition, alpha-linolenic acid-free parenteral nutrition for 46 months was not associated with clinically significant neurological dysfunction. PMID- 3099018 TI - Are hospitals the only place for clinical training of undergraduates? PMID- 3099016 TI - Successful pregnancy outcome using total parenteral nutrition from the first trimester of pregnancy. AB - A 27-yr-old gravida 3, para 2 was supported from the 8th week of pregnancy by intermittent daily total parenteral nutrition (TPN) following the loss of her small bowel. Nutrient intake was adjusted by monitoring nitrogen balance and the rate of increase in fetal cranial enlargement. Maternal calcium balance proved difficult to maintain, since massive urinary Ca+2 losses occurred during infusion of nutrients (576 +/- 2 mg/12 hr on TPN compared to 47 +/- 12 mg/12 hr off). This increase in urine Ca+2 was due to depressed Ca+2 reabsorption by the kidney (87.1 +/- .7 vs 98.1 +/- .3%) and increased filtered load (4623 +/- 241 mg/12 hr vs 2591 +/- 329). Initially calcium balance was -180 mg/day. Nitrogen balance assessed by total stool and urine nitrogen was 1.1 g/24 hr, which was judged to be suboptimal. Deficits were corrected by increasing nitrogen intake, lengthening the duration of infusion and the oral administration of elemental calcium during periods off infusion. A normal fetus was delivered vaginally without complications at 351/2 weeks. This patient demonstrates that normal fetal growth and development as well as appropriate maternal weight gain and nitrogen balance can be maintained throughout pregnancy, including the first trimester, by intermittent daily TPN. PMID- 3099017 TI - Rabbit care unit for intravenous feeding and metabolic studies. AB - A simple rabbit care unit for peripheral intravenous feeding and metabolic studies was developed. The unit consists of six aluminum boxes with a common cover. Inverted T-shaped mobile supports hanging from the upper horizontal part of a frame hold the infusion lines. The side walls of the box prevent the rabbit from turning around, but other movements are possible. After initial training with 21 surgically treated animals, there was only one early anesthetic death among the subsequent 21 rabbits (4.8%). There was one late death (4.8%), and one animal was slightly, and two animals clearly, deteriorated. The ear vein cannula had to be changed in one-third of the animals not more than 3 days from the outset. Problems associated with the infusion systems or urinary bladder catheterization were minor. The results showed that it is practical to infuse rabbits via a peripheral intravenous route in a semi-restraining metabolic unit. The cases of late death and deterioration can be explained in part by the stress of experimental conditions with starvation and surgery, rather than by the effect of the metabolic unit alone. With previous experience in treating rabbits, we find the period required to learn this technique is short. PMID- 3099019 TI - Isonymy and inbreeding in the population of Jhelum (Punjab). PMID- 3099020 TI - Congenital abnormalities of genital tract--vaginal defects. PMID- 3099021 TI - Congenital abnormalities of genital tract--uterine malformation. PMID- 3099022 TI - Effect of oral and injectable contraceptives on low density and high density lipoproteins. PMID- 3099023 TI - Squamous cell carcinoma of nasal septum. PMID- 3099024 TI - Perspectives of economics in medicine. PMID- 3099025 TI - Long-term management of patients with cardiac valve prostheses. AB - Marked improvements have been achieved in the results of valve replacement due to recent developments in cardiac valve prostheses, surgical procedures, myocardial protection methods, and supportive techniques. Since 1974, the aortic valve has been replaced with mechanical valves and the mitral valve with biological valves at our institution. During a cumulative follow-up of 1024 patient-years after 306 valve replacements (126 AVR, 148 MVR and 32 AVR + MVR), the 10-year survival rates were 88% for AVR, 72.6% for MVR and 77.5% for AVR + MVR. The cardiac function of 90% of the survivors was evaluated as Class I or II according to NYHA Functional Classification. As for valve-related postoperative complications, thromboembolism was observed in 2.3%/pt-yr, hemorrhage in 0.5%/pt-yr, prosthetic valve endocarditis in 1.3%/pt-yr, perivalvular regurgitation in 1.3%/pt-yr and valve malfunction in 1.1%/pt-yr. Of the causes of late deaths, 62.5% were related to valve complications. Re-replacement of the prosthesis was necessary in 17 patients due to valve-related complications, and early death occurred in 1 (5.9%) of these 17. While cardiac valve replacement contributes to improvements in the quality of the patients' long-term postoperative life, currently employed artificial valves are still not ideal with regard to their materials and design, and re-replacement may become necessary in the late postoperative period. Therefore, in addition to selection of the appropriate valve prosthesis for different disorders and optimal prevention of valve-related complications, early diagnosis by non-invasive techniques and early treatment of these complications if they have occurred are of particular importance for the long-term management of patients following cardiac valve replacement. PMID- 3099027 TI - [Effects of halothane, trimetaphan and nifedipine on hepatic blood flow in cats during upper abdominal surgery]. PMID- 3099028 TI - [A clinical bacteriological efficacy study on a fosfomycin otic solution]. AB - Fosfomycin (FOM) otic solution was administered to 587 patients with suppurative otitis media infections including 190 patients in the dose-establishment test, 126 patients in the open clinical trial and 271 patients in the double blind test. Various bacteria were detected in the 549 cases in which bacteriological investigation was possible. Main bacteria detected from the above cases were S. aureus (261 strains, 47.5%), P. aeruginosa (93 strains, 16.9%), coagulase negative Staphylococci (CNS) (89 strains, 16.2%), Providencia spp. (35 strains, 6.4%) and Proteus spp. (28 strains, 5.1%). Twenty-seven strains of anaerobic bacteria (4.9%) were also detected. The MIC of FOM, and the reference drug, chloramphenicol (CP), fradiomycin (FRM), cefmenoxime (CMX) and cephalexin (CEX), were determined up to a concentration of 800 micrograms/ml with inoculum sizes of 10(6) and 10(8) CFU/ml. About 30% of S. aureus was multi-drug resistant, including methicillin and cephems, but FOM showed excellent antibacterial activity against it. The FOM had superior antibacterial activity against P. aeruginosa to CP, FRM and CMX, and was also active against other bacteria. The antibacterial activity of FOM was inferior to other drugs against CNS, Enterobacter spp., P. putida and P. cepacia. The detection rate of these bacteria, however, was low and since their role as causative organisms is not well defined, the inferior activity of FOM has no effect on the bacteriological evaluation of FOM. Since the concentration in the tympanic cavity about 1 hour after the administration of 3% FOM solution was estimated to be 2,000 to 3,000 micrograms/ml, it could be presumed that bacteria inhibited by 800 micrograms/ml of FOM at an inoculum size of 10(8) CFU/ml would be eradicable. The low ototoxicity of FOM is likely due to its characteristic as an inhibitor of bacterial cell wall synthesis. From these results, 3% FOM otic solution may be considered as a remarkably useful topical preparation for the treatment of suppurative otitis media. PMID- 3099026 TI - Long-term management of bradyarrhythmias following open heart surgery: surgical A V block and sick sinus syndrome after surgery for secundum atrial septal defects treated with permanent cardiac pacing. AB - Postoperative clinical findings from 25 patients with surgical A-V block and 12 with SSS following surgery for ASD who received permanent pacemakers were analyzed in order to consider the long-term management of postoperative bradyarrhythmias. Surgical A-V block: Episodes of Adams-Stokes were observed in 11/25 patients before pacemaker implantation, and in 6 of these (55%) the onset of episodes occurred more than a year after open heart surgery. Of 8 cases for which ECG's during Adams-Stokes were available, 2 had bifascicular or trifascicular block which progressed to complete A-V block below the His bundle. The 6 others (75%) had ventricular tachycardia or ventricular flutter fibrillation during Adams-Stokes. 2 of these had blocks above the His bundle. 4/25 had improvement of complete A-V block within a month. Following pacemaker implantation, 3 died of heart failure and 3 of sudden death. 5 year survival was 70%. Therefore, surgical A-V block requires careful long-term management, and the presence of ventricular tachyarrhythmias as well as the location of block are important predictors of patient risk. SSS after surgery for ASD: 10/12 patients had Adams-Stokes, of which 6 (60%) had initial onset over 5 years after surgery, and 9 had paroxysmal atrial flutter and fibrillation which coincided with the onset of Adams-Stokes. 3 of 7 patients (42%) for whom preoperative ECG's were available had sinus bradycardia. Thus, SSS after ASD surgery may be preceded by preoperative deterioration of sinus node function and succeeded by late onset of Adams-Stokes, necessitating pre- and postoperative assessment of sinus node function. The presence of atrial tachyarrhythmias also serves as an important indicator of the severity of SSS after ASD surgery. The onset of Adams-Stokes varied by patient over a wide range of time, emphasizing the need for careful long-term follow-up. Clinical symptoms and prognosis were affected by tachyarrhythmias as well as the severity of the bradycardia. Therefore, the presence of ventricular/atrial tachyarrhythmias is an important factor in the long-term management of postoperative bradyarrhythmias. PMID- 3099029 TI - [Cefsulodin concentration in exudates from drainage of patients with acute peritonitis following intravenous administration]. AB - Cefsulodin (CFS), a new antipseudomonal cephalosporin, shows a potent antibacterial activity against Pseudomonas aeruginosa and some Gram-positive bacteria, whereas it shows low activity against many Gram-negative rods. Against clinical isolates of P. aeruginosa, CFS was about 10 times more active than sulbenicillin and carbenicillin, and had a similar activity to gentamicin and dibekacin. The CFS was administered by an intravenous bolus injection at a dose of 1 g to each of 14 patients operated for acute peritonitis with drainage or radical mastectomy with drainage to treat breast cancer. These cases included 3 of localized peritonitis due to perforative appendicitis, 3 of diffuse peritonitis due to perforative duodenal ulcer, 2 of panperitonitis due to intestinal obstruction and perforative sigmoid colon cancer, 4 of subacute cholangitis, localized peritonitis T-tube choledochal drainage due to choledocholithiasis, and 2 of breast cancer. Materials from drain exudate were taken at intervals with sterilized paper discs and CFS concentrations were determined by the paper disc bioassay method with P. aeruginosa NCTC 10490 as the test organism. Serum concentrations of CFS just after injection reached 135.4 +/- 66.1 micrograms/ml, and they were 2.7 +/- 1.5 micrograms/ml at 6 hours after injection. Concentrations in purulent exudates of patients with acute peritonitis increased quickly after intravenous bolus injections, and reached maximum levels relatively early after injection in cases 2 to 3 days after operation. In cases 10 to 13 days after operation, CFS levels were comparatively low and reached to peak levels at 4 to 5 hours after injection. Levels of CFS in purulent exudate tended to increase in proportion to the severity of symptoms, as did CFS levels in appendix wall. Pseudomonas spp. were not isolated in this study, but MICs of CFS were mostly around 1.56 to 3.13 micrograms/ml when clinically isolated Pseudomonas spp. were present at 10(6) cells/ml. Levels of CFS in infected exudate were higher than the above MIC values against Pseudomonas spp. Therefore, CFS were a useful drug for the chemotherapy against pseudomonal infections. PMID- 3099030 TI - [Ultrastructural study of rat mammary tumors and human breast cancer cells following treatment with tamoxifen]. AB - In order to predict the efficacy of hormonal therapy for breast cancer patients, early ultrastructural changes of rat mammary tumors and human breast cancer cells have been studied following treatment with tamoxifen. Following the treatment, complex nuclear bodies (CNB) were increased, and ring-shaped nucleoli were observed in both the rat mammary tumors and the human breast cancer cells. In the tamoxifen-treated human beast cancer patients, CNB increased, as estrogen receptor concentration rose. Shrunken nucleli and intranuclear rodlet were observed only in the tamoxifen-treated human cancer patients. PMID- 3099031 TI - [Thymidylate synthase inhibition in malignant tumors after oral administration of UFT]. AB - Surgical resection of solid tumors was undertaken five to six hours after the oral administration of UFT (300-500 mg/body) in five patients, who were (then) assayed for 5-fluorodeoxyuridylate (FdUMP), total dTMP synthase (TS) and non FdUMP-bound, free enzyme. Three patients had gastric cancer, and two had mammary cancer. Control solid tumors were obtained without, the drug in eight patients. Six patients had gastric cancer. Eight had mammary cancer. Total TS averaged 2.04 p mol/g in the malignant tissues. TS inhibition averaged 40.1% to 57.1% in gastric cancer and 17.1% to 52.7% in mammary cancer. These data suggest that TS inhibition after oral administration of 5FU derivatives may be usefully studied for biochemical parameters of mechanisms of drug resistance. PMID- 3099032 TI - [von Recklinghausen's disease associated with pheochromocytoma--an autopsy case report and review of 24 cases in the Japanese literature]. AB - A 56-year-old woman was admitted because of vomiting and right hypochondralgia. Since she was 25 years old, she had been sick with neurofibromatosis. Systemic neurofibromatosis with cafe-au-lait spots, blood hypertension and tenderness on the right hypochondrium were found. Ultrasonic examination revealed a right adrenal mass. Levels of serum catecholamines were elevated. She developed ileus and died of shock from the release of adrenal catecholamines. Postmortem examination showed right adrenal pheochromocytoma. The tumor measured 11.5 X 8 cm and weighed 25 gm. Von Recklinghausen's disease associated with pheochromocytoma is very rare, and only 24 cases have been reported in Japan. We present our case here with a review of the literature. PMID- 3099034 TI - [Analysis of antigens against anti-platelet antibody detected in patients with EDTA-dependent pseudothrombocytopenia]. PMID- 3099033 TI - [Huge Virchow's metastasis in gastric cancer made resectable by hyperthermochemoradiotherapy]. AB - A 75-year-old woman who had undergone gastrectomy for gastric cancer at the age of 61 developed a huge left supraclavicular tumor (15 X 10 X 10 cm) suspected of being Virchow's node. She was treated with hyperthermochemoradiotherapy (HCT therapy). After 10 sessions of radiofrequency hyperthermia by a Thermotron RF8, irradiation with 52.8 Gy of 60Co and injection of 8 mg of MMC, the tumor mass decreased by 77% on CT. The histologically resected specimen revealed coagulation necrosis in almost all areas. This case, which was considered HCR-therapy effective, was estimated as Grade 3 according to The General Rules for the Gastric Cancer Study (The 11th edition.) PMID- 3099035 TI - [Chemical components of pathogens and the mechanism of their virulence: Pseudomonas aeruginosa vaccine]. PMID- 3099037 TI - [Ossification of the thyrohyoid ligament--a case report]. PMID- 3099036 TI - [Immunochemical analysis of two M components (IgG-kappa, IgM-kappa) in a patient with malignant melanoma]. PMID- 3099038 TI - Effects of ethanol on the blood gas and acid-base state in hypoxic rats. PMID- 3099039 TI - A radioimmunoassay using 125I-protein A for the determination of red cell RH1 (Rh0, D) antigen. PMID- 3099040 TI - [Diary of a woman physician suffering from cancer. 12. Struggle with intestinal obstruction]. PMID- 3099041 TI - Cytoprotective action of mast cell stabilizers against ethanol-induced gastric lesions in rats. AB - We examined the effects of FPL-52694 and disodium cromoglycate (DSCG), mast cell stabilizers, on HCl X ethanol-induced gastric lesions in rats and investigated the factors involved in their protection. Oral (p.o.) administration of 1 ml of HCl X ethanol (60% in 150 mM HCl) induced linear hemorrhagic lesions in the gastric mucosa within 1 hr. FPL-52694 (1-30 mg/kg), given both p.o. and intraperitoneally (i.p.), prevented these lesions in a dose-related manner. DSCG (3-30 mg/kg) also dose-dependently reduced the formation of these lesions when this agent was given i.p. The protective effects of these drugs on HCl X ethanol induced lesions were significantly attenuated by pretreatment with indomethacin (5 mg/kg, s.c.). Both gastric acid secretion and transmucosal potential difference were significantly reduced by topical application of FPL-52694 (greater than 10 mg/kg), but were not affected by i.p. administration of FPL 52694 and DSCG. On the other hand, gastric motor activity measured as intraluminal pressure recordings was significantly inhibited for 2 hr by both FPL 52694 (p.o. and i.p.) and DSCG (i.p.), and these effects were also significantly antagonized with prior administration of indomethacin. A significant relationship was found between the effects of these two drugs on the lesion index and the motility index (r: 0.9214, P less than 0.01), but not other factors. These results suggest that mast cell stabilizers such as FPL-52694 and DSCG protect the gastric mucosa against HCl X ethanol through a systemic action, probably mediated with endogenous prostaglandins. Although the mechanism of cytoprotection remains unknown, this property may be related to their inhibitory effects on gastric motor activity. PMID- 3099043 TI - The inhibitory effects of calmodulin antagonists on the endothelium-dependent relaxation in rabbit aorta. AB - Effects of trifluoperazine (TFP, 10(-5) M), trifluoperazine sulfoxide (TFP-SO, 10(-5) M), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7-, 10(-4) M), N (6-aminohexyl)-1-naphthalenesulfonamide (W-5, 10(-4) M) and verapamil (10(-5) M) on the endothelium-dependent relaxation of the contractions induced in the isolated rabbit aorta were studied. Carbachol (10(-6) - 10(-6) M) and A23187 (10( 8) M) relaxed the contraction due to norepinephrine (10(-6) M and histamine (10( 5) M) in the aorta with endothelium. TFP and W-7 completely inhibited the relaxation induced by carbachol and A23187. In contrast, TFP-SO and W-5, which have lower affinity to calmodulin, had little or no effect on either the carbachol- or A23187-induced relaxation. An organic calcium antagonist, verapamil, did not change the relaxation induced by carbachol or A23187. W-7 did not modify the relaxing effect of sodium nitroprusside (10(-8) - 10(-6) M) which is not mediated by endothelium. These results suggest that either formation or release of endothelium-derived relaxing factor involves the process mediated by calmodulin in the rabbit aorta. PMID- 3099042 TI - Enhanced chemosensitivity of cells from malignant effusions under condition of exposure to high temperature. AB - Utilizing a clonogenic assay, the effects of hyperthermia and selected chemotherapeutic drugs on growth of cells from malignant effusions were studied. Fourteen of 25 samples obtained from 25 patients with various carcinomas formed at least 30 colonies per plate. Exposure of the cells to heat at 42 degrees C for 1 hr before the plating slightly inhibited the colony growth. The drugs, adriamycin (AM) and mitomycin C (MMC), were tested at 3 different concentrations. When the cells were treated with these two drugs for 1 hr at 42 degrees C, the percent of surviving colonies was significantly decreased, as compared to findings at 37 degrees C, in both groups, at 3 different concentrations. The combination of drugs and hyperthermia appeared to function synergistically in one third of such cases. These results suggest that cells from malignant effusions in patients with various carcinomas were more sensitive to AM or MMC, under condition of a higher temperature (42 degrees C). PMID- 3099044 TI - [Noradrenaline denervation supersensitivity of the urethra in female mongrel dogs]. PMID- 3099045 TI - [A case of renovascular hypertension associated with neurofibromatosis]. PMID- 3099046 TI - Synergistic antiproliferative effect of human recombinant interferons and retinoic acid in cultured breast cancer cells. AB - A combination of retinoic acid (RA) and human recombinant DNA-derived interferon gamma (Hu-IFN-gamma) was tested with respect to the growth inhibitory action on several human mammary carcinoma cell lines (ZR-75.1, 734-B, MCF-7, and BT-20), a human lung carcinoma cell line (CCL-185), and a human laryngeal carcinoma cell line (HEP-2). The mammary carcinoma cell lines were all sensitive to Hu-IFN gamma, and 2 of them (ZR-75.1 and 734-B) were also affected by RA. The combination of both substances led to a pronounced synergistic amplification of growth inhibition in ZR-75.1 and 734-B cells. RA also increased the antiproliferative activity of Hu-IFN-gamma in the RA-resistant BT-20 cells and to a less pronounced degree in MCF-7 cells. In contrast to these findings, no synergistic effects were observed between Hu-IFN-gamma and RA in CCL-185 and HEP 2 cells. Human recombinant DNA-derived interferon-alpha 2 amplified the action of RA only in BT-20 cells, but it did not act synergistically with RA in the other cell lines tested. PMID- 3099047 TI - Relationship between anaphase aberrations and carcinogenicity in the trout embryo microinjection assay. AB - An increased incidence of anaphase aberrations was observed in the tissues of rainbow trout embryos (Salmo gairdneri) within 96 hours of exposure to mitomycin [(MM) CAS: 50-07-7; 50 and 100 ng/embryo] and aflatoxin B1 [(AFB1) CAS: 1162-65 8; 13 and 25 ng/embryo] with the use of the trout embryo microinjection assay. High numbers of anaphase aberrations in embryos exposed to MM were associated with low mitotic indices, cell pyknosis, and high embryo mortalities. When the anaphase aberration data for embryos exposed to AFB1 were compared to previously reported carcinogenesis data from the microinjection assay, the incidence of anaphase aberrations in embryos did not show the same quantitative variations as the incidence of hepatic carcinomas in adult trout. While anaphase aberrations may be an indicator of the clastogenic effects of chemicals on fish embryos, it is unlikely that these aberrations can be used as an early indicator of a carcinogenic response in the trout embryo assay. PMID- 3099048 TI - Inhibition of intestinal carcinogenesis in rats: effect of difluoromethylornithine with piroxicam or fish oil. AB - An inhibitor of ornithine decarboxylase, difluoromethylornithine (DFMO), and two inhibitors of prostaglandin biosynthesis, piroxicam and menhaden fish oil, were examined for their effect on intestinal tumorigenesis in male Sprague-Dawley rats fed a 5% fat semisynthetic diet. Each agent was given individually in one of two doses as follows: DFMO, 0.05% and 0.1% in the drinking water; piroxicam, 65 mg/kg diet and 130 mg/kg diet; and menhaden fish oil, 1.25% and 2.50% of the diet. Additional animal groups were given combinations of the lower dose of DFMO and the lower dose of either piroxicam or fish oil. Intestinal tumors were induced by sc injections of azoxymethane (AOM; CAS: 25843-45-2) at 8 mg/kg (body wt) weekly for 8 weeks. Test diets were started 1 week prior to the first dose of AOM, and the rats were sacrificed 26 weeks later. Rats that received either dose of DFMO or the high dose of piroxicam developed significantly fewer intestinal tumors compared to controls. The low dose of piroxicam and the fish oil given at either dose level had no effect. The combination of the low dose of DFMO and the low dose of piroxicam reduced tumor formation more than either dose of DFMO alone, whereas the low dose of DFMO and fish oil together was no more effective than either dose of DFMO alone. These results show that a combination of a small amount of DFMO and piroxicam, each acting through a different mechanism, exerts an additive inhibitory effect on intestinal tumor formation in rats. PMID- 3099049 TI - Gamma interferon priming of mouse and human macrophages for induction of tumor necrosis factor production by bacterial lipopolysaccharide. AB - Priming of macrophages from both murine and human sources by recombinant immune interferons from Escherichia coli (r-IFN-gamma s) and activation by lipopolysaccharide (LPS) resulted in the production of tumor necrosis factor (TNF). r-IFN-gamma alone did not induce TNF production by macrophages; for this to occur, the second signal provided by small amounts (nanograms) of LPS was required. The small amounts of LPS alone were insufficient to activate the macrophages for TNF production. Priming by r-IFN-gamma was not necessary when larger amounts of LPS were employed, although an enhancement of yield resulted. Priming could also be demonstrated in vivo. Inoculation of r-IFN-gamma into mice resulted in increased yields of TNF following LPS challenge 12 hours later. PMID- 3099050 TI - Tumorigenesis in athymic nude mouse skin by chemical carcinogens and ultraviolet light. AB - A variety of established skin tumorigenesis protocols were tested for efficacy on athymic nu/nu mice (BALB/c background) and compared on euthymic nu/+ counterparts. Chemical carcinogens and UV light were applied to the ears of 10 mice of each sex and genotype for each group. Treatments were: 0.5 mg 7,12 dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6] to each ear; 0.125 mg DMBA to each ear, followed by 0.1 microgram 12-O-tetradecanoylphorbol-13-acetate [(TPA) CAS: 16561-29-8] twice weekly for 56 weeks; 0.2 mg N-nitroso-N-methylurea [(NMU) CAS: 684-93-5; 1% in acetone, 20 microliter] to each ear; 0.1 mg NMU to each ear weekly for 30 weeks; 0.2 mg NMU to each ear, followed by TPA twice weekly for 56 weeks; two ip doses of N-nitroso-N-ethylurea [(NEU) CAS: 759-73-9; 25 mg/kg each], followed by TPA twice weekly topically for 56 weeks; and exposure to sunlamps (250- to 400-nm emission) two or three times per week for 20 weeks, for a total dose of 3.7 X 10(5) J/m2. The chemical treatments caused mainly squamous papillomas and carcinomas, sebaceous adenomas and adenocarcinomas, and basal cell tumors, which appeared both on the skin of the ears and elsewhere. UV light caused squamous tumors, basal cell tumors, and sarcomas. Ear skin of the nu/nu mice developed significantly more squamous tumors than those of nu/+ mice after DMBA-TPA, NMU-TPA, NEU-TPA, repeated NMU, or UV light. Similar results were obtained for the skin of the heads and bodies. Even a single dose of NMU caused a few tumors on the nude, but not the euthymic, mice. A single dose of DMBA caused primarily sebaceous adenomas, distributed at random over the entire bodies. These results show that, contrary to previous reports, nude mice are sensitive to skin tumorigenesis, more so than euthymic nu/+ mice similarly exposed to diverse types of carcinogen and treatment protocols. PMID- 3099052 TI - [Long term care in the U.S.A.--nursing homes]. PMID- 3099051 TI - Prevention by vitamin E of experimental oral carcinogenesis. AB - In the standard model for hamster buccal pouch, using a 0.5% solution of 7,12 dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6], it was shown that vitamin E (alpha-tocopherol) inhibited carcinogenesis. With a less potent carcinogen (0.1% DMBA), vitamin E was shown to prevent tumor development. Eighty (total) male and female Syrian hamsters (Mesocricetus auratus) were divided into 4 equal groups. After 28 weeks, animals in group 2 that had left buccal pouches painted with 0.1% DMBA (in heavy mineral oil) three times/week and that had been given 10 mg DL alpha-tocopherol on alternate days (i.e., two times/wk) showed no tumors there. However, the pouches of group 1 animals that had been similarly painted with DMBA but that had received no vitamin E demonstrated grossly and microscopically the presence of epidermoid carcinomas. PMID- 3099053 TI - [Immunological changes after massive blood transfusion (review of the literature)]. PMID- 3099054 TI - [Effect of nitroglycerin on intraocular pressure]. PMID- 3099055 TI - [Functional service--challenge for nursing. Historical development/description]. PMID- 3099056 TI - [Old age, ethical and medical limits for diagnostic and therapeutic interventions]. PMID- 3099057 TI - [Special methods in the nursing of elderly patients in endoscopy during outpatient treatment]. PMID- 3099058 TI - [Nursing in the intensive care unit]. PMID- 3099059 TI - [Intensive and psychological care for severely injured accident victims]. PMID- 3099060 TI - [Medical appliance legislation--effect on manufacturer and user]. PMID- 3099061 TI - [Methods of organisation of occupational safety and accident prevention]. PMID- 3099062 TI - [Team work: the cooperation between physician and nursing personnel in the field of anesthesia]. PMID- 3099063 TI - [Development of enteral diets]. PMID- 3099064 TI - Colonization resistance against Pseudomonas aeruginosa in gnotobiotic mice. AB - Gnotobiotic (GB) mice were colonized with various groups of intestinal bacteria to determine which members of the indigenous flora would exert colonization resistance against Pseudomonas aeruginosa. P. aeruginosa was cultured from the faeces at levels of 10(3)-10(4) cells/g in GB mice inoculated with either the combination of bacteroides and clostridia obtained from conventional (CV) mice or the combination of bacteroides, lactobacilli and clostridia obtained from limited flora mice. The combination of lactobacilli and clostridia from CV mice also did not eliminate P. aeruginosa from GB mice. However, P. aeruginosa was not detected in the faeces of GB mice by 14 days after inoculation with the combination of bacteroides, lactobacilli and clostridia obtained from CV mice. Thus, a complex indigenous flora consisting of bacteroides, lactobacilli and certain clostridia obtained from CV mice but not clostridia obtained from limited flora mice is required to exert complete colonization resistance against P. aeruginosa in GB mice. PMID- 3099065 TI - 3-Hydroxy-3-methylglutaryl-coenzyme a lyase deficiency: a review. AB - Children with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMG-CoA-LD; McKusick 24645), have inherited two areas of metabolic weakness. Firstly, they are unable to metabolize fully the carbon skeleton of leucine, and secondly, they cannot make ketone bodies in response to prolonged fasting. In the first year of life infants with HMG-CoA-LD run a high risk of developing severe hypoglycaemia which can lead to death if prompt intervention does not occur. The metabolic crisis develops when the infant is first introduced to dietary protein soon after birth, or later, when a reduced intake of glucose, often during a viral infection, results in a drain on the infant's circulating glucose levels. However, where diets are adequately adjusted to limit protein and fat intake, the metabolic handicaps of individuals with HMG-CoA-LD are not exposed and they are virtually symptomless. As children with HMG-CoA-LD grow older the incidence of hypoglycaemic attacks diminishes and they usually develop normally. This article reviews literature on cases of HMG-CoA-LD and interprets data on altered metabolism in these children. PMID- 3099066 TI - Galactosylcerebrosidase activity in tissues of twitcher mice with and without bone marrow transplantation. AB - Galactosylcerebrosidase activity was measured and compared in brain, liver, tongue and bone marrow of twitcher (twi/twi) mice, an animal model of human Krabbe's disease, and in normal heterozygotes (twi/+). There was a reduction in enzyme activity in all tissues in twi/twi mice, but the magnitude of the reduction varied, being greatest in the bone marrow (3% of the heterozygote activity). Twitcher mice were transplanted with normal bone marrow cells at birth without prior irradiation, and just over half had a significant increase in their bone marrow enzyme activity, but not in other tissues. The fourfold increase in the enzyme activity was not associated with any improvement in the clinical picture or prolongation of lifespan. PMID- 3099067 TI - Tetrahydrobiopterin non-responsiveness in dihydropteridine reductase deficiency is associated with the presence of mutant protein. AB - Correlation of the response to a load of tetrahydrobiopterin (BH4) in dihydropterin reductase (DHPR) deficient patients to the type of mutation in these patients has led to the conclusion that 4 patients without mutant DHPR molecules in their cells respond to the BH4 load, whereas 3 patients with mutant DHPR in their cells do not respond. Intravenous injection of BH4 in 1 of the cases not responding to BH4 again showed no response. PMID- 3099068 TI - Treatment of chronic congenital lactic acidosis by oral administration of dichloroacetate. AB - Sodium dichloroacetate (DCA) was administered orally at a dose of 50 mg per kg body weight twice or three times per day to a newborn infant with lactic acidosis of unknown cause (patient 1) and to a 15-year-old boy with mitochondrial encephalomyopathy associated with lactic acidosis (patient 2). In patient 1, during treatment with DCA, DCA accumulated in the blood judging from the findings that the urinary excretion of DCA increased cumulatively and the blood lactate level rapidly decreased to the normal range. In patient 2, the blood DCA level gradually increased during treatment to a concentration of 250 micrograms ml-1 and the blood lactate level decreased and was maintained within the normal range. DCA was detected in the brain (25 micrograms g tissue-1) and the liver, kidney and muscle (33.8, 33.8 and 26.3 micrograms g tissue-1, respectively) obtained at autopsy of patient 1, and in the cerebrospinal fluid of patient 2 at a concentration of 125 micrograms ml-1 when the blood concentration was 250 micrograms ml-1. The lactate levels in the cerebrospinal fluid decreased from 7 and 4 mmol l-1 to 2.4 and 2.6 mmol l-1 in patients 1 and 2, respectively. Thus DCA may be useful in clinical treatment of chronic congenital lactic acidosis because it seems to cross the blood-brain barrier. However, it must be given at non-toxic doses, determined by monitoring the concentrations of lactate and DCA in the blood, because orally administered DCA tends to accumulate in tissues. PMID- 3099070 TI - Neuropathological and clinical correlations in Hurler disease. AB - We report studies on two patients (1 and 2) with Hurler disease. They both had all of the non-neurological features of Hurler disease to a similar and extreme degree and similar signs of brain damage on computed tomography. However, intellectual function was unusually well-preserved in patient 1, but seriously and typically impaired in patient 2. The reason for this discrepancy has been investigated by reference to the neuropathological findings, the results of alpha L-iduronidase assays using different substrates and comparisons to other cases (patients 3 and 4). We suggest that patient 1 is an unusual variant of the disease who may have had a very low residual alpha-L-iduronidase activity in neuronal cells only, and that this could not be demonstrated by either enzyme assays on whole brain using the 4-methylumbelliferyliduronide substrate (Crow et al., 1983) or in studies on fibroblast lysates using a radioactive disaccharide substrate. PMID- 3099069 TI - Kinetic abnormalities of carbamyl phosphate synthetase-I in a case of congenital hyperammonaemia. AB - A sensitive direct colourimetric method has been employed to measure kinetic parameters and pH dependence of carbamyl phosphate synthetase-I, in a liver sample from a 2 1/2-month-old girl, who died from complications of a late developing congenital hyperammonaemia. The residual activity of carbamyl phosphate synthetase-I was 25%, whereas other urea cycle enzymes were within normal range. Apparent Km for ammonium ion (0.73 mmol/L) was significantly increased (normal range 0.24-0.51). Km for bicarbonate ion was normal, while Km for NAG showed a slight variation from normal. The pH dependence curve of the patient's enzyme was flat, as compared to two controls showing pH optima at 7.8. Radial immunodiffusion (Mancini) of the abnormal enzyme against human enzyme antiserum gave a cross-reacting material of 10-20%. The methodological approach presented can be used to characterize abnormal enzymes in cases of partial deficiency with only 100-200 mg of liver tissue. PMID- 3099071 TI - Lysosomal protein degradation in experimental hyperphenylalaninaemia. AB - The influence of alpha-methylphenylalanine-induced hyperphenylalaninaemia (HYP) on the lysosomal protein degradation system in brain and liver of suckling rats was investigated. In both tissues cathepsin D and L activities, measured at 5, 10 and 15 days post partum (p.p.), exhibited no differences between experimental and control animals. N-Acetyl-beta-D-glucosaminidase (NAGase) activity in brain, measured at 10 and 15 days p.p., was not affected by HYP either. The release of valine and lysine from liver and brain homogenates respectively, serving as a measure for the lysosomal content of degradable proteins, was not influenced by HYP. Lysosomal integrity during incubation of homogenate was monitored by the recovery of NAGase activity in the cytosolic supernatant, and by the relative NAGase activity in total homogenates in the absence of the lysosome disrupting detergent Triton X-100. In conclusion, experimental HYP appears unlikely to influence the lysosomal protein degradation system in brain and liver of suckling rats. PMID- 3099072 TI - An individual with high plasma lysosomal enzymes. PMID- 3099073 TI - Biotinidase deficiency: metabolites in CSF. PMID- 3099074 TI - Pubertal maturation and classical phenylketonuria. PMID- 3099075 TI - 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency. PMID- 3099077 TI - Biosynthesis of peroxisomal beta-oxidation enzymes in infants with Zellweger syndrome. PMID- 3099076 TI - Molecular basis of ornithine transcarbamylase deficiency in spf and spf-ash mutant mice. PMID- 3099078 TI - Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome and NADH-CoQ reductase deficiency. PMID- 3099079 TI - Bone marrow transplantation in Niemann-Pick mice. PMID- 3099080 TI - Molecular cloning of cDNAs for argininosuccinate lyase and arginase of rat liver. PMID- 3099081 TI - A new type of hyperlysinaemia due to a transport defect of lysine into mitochondria. PMID- 3099083 TI - Pathogenesis of Sarcocystis falcatula in the budgerigar. I. Early pulmonary schizogony. AB - Sarcocystis falcatula is a protozoan parasite which obligatorily alternates its definitive host, the opossum (Didelphis virginiana), and a uniquely wide range of avian intermediate hosts. The disease produced by this coccidian parasite in intermediate hosts was studied in the budgerigar bird (Melopsittacus undulatus). The ultrastructure of pulmonary sporozoites, meronts and merozoites of this Sarcocystis species is described. Early schizogony occurs progressively in pulmonary capillary and in venular and venous endothelial cells. PMID- 3099082 TI - Double immunoenzyme staining method for analysis of tissue and blood lymphocyte subsets with monoclonal antibodies. AB - Double immunoenzymatic method for sequential staining with two different monoclonal murine antibodies and two different enzymes was shown to be useful in defining hematopoietic cell subpopulations in human tissues and blood. The method allows for the identification, localization, and enumeration in the same section of distinct cell populations. Air-dried smears of cell mixtures can be stained. The optimal sequence of enzymes/substrates was: horseradish peroxidase/3-amino-9 ethylcarbazole followed by the alkaline phosphatase-anti-alkaline phosphatase complex/naphthol AS-MX phosphate. Red-and blue-colored reaction products are easy to view in a light microscope. Combinations of two different mouse monoclonal antibodies or of a mouse monoclonal antibody and polyclonal antiserum made in rabbits or goats can be sequentially applied to the same section or smear thus facilitating a definition of the distribution of two cell populations reactive with these antibodies. The relative distribution patterns in tissues of cells bearing distinctive antigens are important in studies of cellular differentiation and of human pathogenetic processes including neoplasia and transplant rejection. PMID- 3099084 TI - Pathogenesis of Sarcocystis falcatula in the budgerigar. II. Pulmonary pathology. AB - Sarcocystis falcatula is a protozoan parasite which obligatorily alternates its definitive host, the opossum (Didelphis virginiana), and a uniquely wide range of avian intermediate hosts. The disease produced by this coccidian parasite in intermediate hosts was studied in the budgerigar bird (Melopsittacus undulatus). Early schizogony occurs in pulmonary endothelial cells, resulting in endothelial cell hypertrophy, capillary obstruction preceding endothelial lysis, acute endophlebitis, and chronic periphlebitis. These impede outflow of the pulmonary vascular system resulting in interstitial, subpneumocytic, and then air-space edema. The edema is associated with retraction and degeneration of squamous pneumocytic processes, loss of the myelinoid "surfactant" covering over the pneumocytes, and atelectasis of the respiratory labyrinth. Epithelial repair is effected by migration of granular pneumocytes (normally confined to the parabronchi and their atria) down the infundibula and into the respiratory labyrinth. This pattern of injury and repair is comparable to diffuse alveolar damage (acute interstitital pneumonitis) of mammals despite the markedly different structure of the avian lung. The implications of this peculiar tissue tropism are discussed. PMID- 3099085 TI - Asymptotic and dimensionless analysis of the response of living tissue to surgical pulsed CO2 lasers. AB - The mathematical model of the interaction between the radiation of pulsed CO2 lasers and tissue was revisited. Asymptotic calculations were employed to determine upper and lower bounds for the evaporated volume and crater depth. Dimensionless time variables for conduction, beam attenuation by tissue vapors and for damage were introduced. Optimal exposure parameters were identified through a dimensionless analysis. PMID- 3099086 TI - The effects of Mg2+ ions or EDTA on nuclear integrity and apparent subcellular distribution of unoccupied oestrogen receptors in breast cancer cells. AB - Homogenisation and fractionation of cells in the presence of Mg2+ or EDTA resulted in unoccupied oestrogen receptor being recovered in the particulate fraction. Nuclei were partially purified by pelleting at 100,000 g through 41% and 44% (w/w) sucrose (in buffer containing Mg2+ or EDTA), plasma membranes being collected from the top of the 41% barrier. In Mg2+-prepared fractions, both 5' nucleotidase and unoccupied receptor were distributed between plasma membrane, partially-pure nuclei and mitochondrial/microsomal pellets. Lactate dehydrogenase was not a significant contaminant of particulate fractions. In EDTA fractions, the majority of binding activity was in the partially-pure nuclei (which were extensively disrupted) and mitochondrial/microsomal pellets. Little or no binding was found in the EDTA-prepared plasma membranes which were amorphous in appearance. Mg2+-prepared nuclei, freed of membranous contamination by pelleting through 1.8 M sucrose, were intact by electron microscopy but had no 5' nucleotidase or unoccupied receptor. These data suggest that recovery of receptor in partially-pure nuclei during fractionation is not caused by trapping of cytosolic protein but rather by redistributed nuclear receptor having become bound to adhering plasma membrane fragments during homogenisation. Implications for the study of cell-free systems are discussed. PMID- 3099088 TI - A model describing the kinetics of mating in Drosophila. AB - The kinetics of mating in species of Drosophila that copulate for periods of time greater than the duration of experimental observation can be described precisely by an equation that combines second order reaction kinetics with the exponential decay of a lag factor. The two rate constants for this kinetic system were estimated from mating data using a wild-type D. simulans strain, a wild-type D. melanogaster strain, and vestigial mutant D. melanogaster males with wild-type females. The results confirm the applicability of second order kinetics, and demonstrate the usefulness of the model in comparisons of mating rates among strains of flies. In most cases, the model explains more than 95% of the variance in the data, and in addition sheds light on the mechanics of the process of mating. PMID- 3099087 TI - Sequence homologies of glucose-dehydrogenases of Bacillus megaterium and Bacillus subtilis. AB - The sequence homologies of the glucose dehydrogenase subunits of B. megaterium and B. subtilis are compared. From the known B. megaterium aminoacid sequence and the base sequence of the cloned B. subtilis structural gene we predict the B. megaterium structural glucose dehydrogenase gene. Assuming the minimal mutational changes to convert one gene into the other 23 transitions, 30 transversions, 1 inversion, 3 insertion-deletions, but no frameshifts are postulated necessary to interconvert the structural genes. The homology of both enzyme subunits of 85% reflects the close evolutionary distance between B. subtilis and B. megaterium. PMID- 3099089 TI - Circadian rhythms in Drosophila melanogaster: analysis of period as a function of gene dosage at the per (period) locus. AB - Mutations at the per (period) locus of Drosophila melanogaster affect the period of its circadian rhythms. An analysis of published data on strains having duplications and deletions of the per locus indicates that the period is a logarithmic function of the level of the per gene product. The analysis also indicates that period is relatively insensitive to the level of that gene product; a presumed 300% increase in the gene product level produces only a 4.6% decrease in the period. The period of a strain transformed with per+ DNA conforms to the same logarithmic relationship if the level of mRNA in the transformant, which is one-tenth that in the wild type, is considered equivalent to a gene dosage one-tenth the wild type dose of 2, or 0.2. The periods of strains having various doses of mutant per alleles which shorten (pers) or lengthen (per1) the period can be fitted to the same logarithmic function. The analysis may provide an explanation for the partial dominance of pers over per+ and the dominance of per+ over per1, since it suggests that the per1 gene product is nearly inactive while the pers gene product is more than 34 times as active as the wild type product. Analysis of periods of strains heterozygous at the per locus suggests that the per gene product may be a multimeric protein. Three possible roles for the per gene product in circadian rhythmicity are discussed, including a role in synchronizing rhythm-producing cells. PMID- 3099091 TI - Influence of Epilobium extracts on prostaglandin biosynthesis and carrageenin induced oedema of the rat paw. AB - Epilobium species have been used as remedies in folk-medicine for the treatment of pathophysiological processes of the prostata. In this paper the influence of extracts of Herba Epilobii angustifolii L. and Herba Epilobii parviflori Schreb. on prostaglandin biosynthesis and the carrageenin rat paw oedema is described. Aqueous extracts of Herba E. angustifolii reduced the release of prostaglandins I2, E2 and D2 (in the perfused rabbit ear) approximately 5 times more effectively than did similar extracts of Herba E. parviflori. Methanolic extracts were inactive. The aqueous extract of E. angustifolium strongly reduced the carrageenin-induced rat paw oedema whereas that of E. parviflorum was inactive. The chemical nature of the active compound(s) is as yet unknown but flavonoids and sitosterol derivatives can be excluded. PMID- 3099092 TI - Heart and unilateral lung transplantation in the dog. PMID- 3099090 TI - Scrapie, ribosomal proteins and biological information. AB - Consideration of the autocatalytic synthesis of ribosomal proteins leads to a criterion for the infectivity of a foreign proteinaceous species in terms of the biochemical rate constants governing the propagation of errors during the translation of genetic information in a model system. Evidence pertaining to the suggestion that scrapie and its analogues are caused by proteinaceous infectious agents (prions) which replicate by invading the translation process and altering ribosomal specificity is examined. It is found that anomalous aetiological features of scrapie infection are explained by the model. An analysis suggesting that the possibility of prion replication undermines the basis of current molecular biological theory is provided and it is concluded that the exclusive identification of biological information with nucleic acid sequences is unjustified. PMID- 3099093 TI - Lymphocyte populations and TAC-antigen in diffuse B-cell lymphomas. AB - Immune cell populations in 8 diffuse histology B-cell lymphomas were analysed in frozen tissue sections by indirect immunofluorescence to gain insight into their possible modulating influence in these tumors. Use of monoclonal antibodies to identify cellular and extracellular antigens combined with nuclear counterstaining allowed precise quantitation, localization and comparison of T- and B-lymphocyte populations. T lymphocytes clustered in non-random fashion. Areas of high T-lymphocyte density manifested higher T4:T8 ratios than locales with fewer T lymphocytes (p less than 0.05). Few cells had surface antigens (Leu 7, 73.1, OKM1) associated with natural killing. Cells strongly reactive with anti TAC (Interleukin-2 receptor, associated with T-lymphocyte activation) were also T11 reactive and were usually helper (Leu 3) phenotype. In addition, B-lineage lymphoma cells in some tissues reacted with anti-TAC. The pattern of tumor cell reactivity with anti-TAC correlated with Rappaport histologic classification. These findings suggest that non-malignant T lymphocytes modulate B-lymphoma cell growth in situ, and that in some lymphomas the T-cell product IL-2 may be an important local growth factor. PMID- 3099094 TI - T-cell acute lymphoblastic leukemia in Israel: clinical and laboratory features. AB - T-cell acute lymphoblastic leukemia (ALL) comprises a third of the cases of childhood ALL in Israel. This high proportion of T-ALL is most probably due to a deficiency in pre-B/common ALL. The T-ALL patients had significantly worse 4-yr survival compared to standard risk or non-T high risk patients. In view of these special epidemiologic and clinical features a study of the immunophenotype of all consecutive cases of T-ALL and T-non Hodgkin's lymphoma (NHL) observed in our medical center was performed. Twenty-eight ALL and 3 NHL patients were studied and their cells characterized using a panel of monoclonal antibodies, TdT reactivity and E-rosette formation. Assays of the activities of adenosine deaminase (ADA) and purine nucleoside phosphorylase (NP) were also performed. Based on the surface antigen expression, the tumor cells could be classified into one of the three known developmental stages of T cells. It was found that the immunophenotype of the T-ALL cases in Israel was similar to that observed in other countries. Considerable heterogeneity of surface antigen expression was found and in a number of cases the phenotype analysis was not easily reconciled with models of T-cell ontogeny. The activities of ADA and NP were correlated with the developmental stage, as defined by the surface antigenic expression. Contrary to observations on normal T-cells, where ADA activity decreases and NP activity increases as T-cells mature and differentiate, this was not found in the malignant T cells. These findings as well as the existence of atypical immunophenotypes suggest that the leukemic T cell has an abnormal gene expression. PMID- 3099095 TI - Potentiation of hydroxyurea cytotoxicity in human chronic myeloid leukemia cells by iron-chelating agent. AB - The effect of hydroxyurea (HU) was studied in 15 cases of human chronic myeloid leukemia cells (CML) in combination with iron-chelating agent, 2,2-bipyridine (bipyridine). The extent of (3H)thymidine incorporation in CML cells in vitro was taken as an index for the measurement of cytotoxicity. In the present study, we observed a potentiation in HU cytotoxicity by hydrophobic iron-chelator bipyridine (p less than 0.001) resulting in complete DNA biosynthesis inhibition. Both HU and bipyridine were used at a relatively non-toxic concentrations of 10( 4) M and 10 micrograms/ml, respectively. This inhibition was found to be partially reversible and a partial protective action by iron is also demonstrated. The various other metal chelators failed to sensitise CML cells to HU cytotoxicity. Implications with respect to the efficacy in cancer treatment is discussed. PMID- 3099096 TI - Rearrangement of immunoglobulin heavy chain genes and T3 expression in the absence of rearrangement of T-cell receptor beta-chain gene in a patient with T cell malignant lymphoma. AB - We describe the rearrangement of immunoglobulin genes and T3 expression in the absence of rearrangement of T-cell receptor beta-chain genes in a patient with T cell malignant lymphoma. He had a mediastinal mass and his lymphoma cells expressed T-cell antigens (OKT3+, OKT9+, and OKT10+). When we examined genomic DNA from the lymphoma cells, we detected the rearrangement of immunoglobulin heavy chain genes with a germ-line configuration of light chain genes and no rearrangement of T-cell receptor beta-chain gene. These results indicated that the rearrangement of immunoglobulin genes could occur in T-cell malignant lymphoma, and that T3 antigen could be expressed prior to the rearrangement of T cell receptor beta-chain genes under certain circumstances. PMID- 3099097 TI - The c-abl, bcr and C lambda genes are amplified in a cell line but not in the uncultured cells from a patient with chronic myelogenous leukemia. AB - Structural alterations of the oncogenes in human tumors are reported to result from a variety of mechanisms: point mutations, chromosomal translocations and gene amplifications. In over 90% of the cases of chronic myelogenous leukemia (CML), the c-abl oncogene is translocated from chromosome 9 to chromosome 22, and forms in part the Philadelphia (Ph1) chromosome. We have molecularly analysed a double Ph1-positive (Ph1+) cell line, KBM-5 that was established from a patient with CML in the blast-transformed phase (CML-BP). We report that the c-abl, bcr, and C lambda genes are amplified approximately eight-fold in the cell line but not in the fresh uncultured cells from which KBM-5 was derived. PMID- 3099098 TI - Retinoic acid promotes phorbol ester-initiated macrophage differentiation in HL 60 leukemia cells without disappearance of protein kinase C. AB - The ability of retinoic acid (RA) to promote 12-O-tetradecanoyl-phorbol-13 acetate (TPA)-initiated macrophage differentiation was examined in human promyelocytic leukemia cell line HL-60. One-hour exposure to 10 nM TPA and subsequent exposure for 48 h to 1 microM RA following removal of TPA rapidly induced the macrophage phenotype in 65% of the cells. This effect was comparable to continuous exposure for 48 h to TPA alone, but contrasted with the absence of macrophage-like cells after RA treatment alone or the induction of 10% of the cell population to a macrophage phenotype after 1-h exposure to TPA. The effect of TPA + RA was accompanied by increased cell adherence and increased nonspecific esterase activity but not by a change in the reduction of nitroblue tetrazolium. Protein kinase C (PK-C) activity was increased 35-40% in cells treated for 1 h with TPA alone or after subsequent exposure to RA. Cells treated for 48 h with RA exhibited a 2-fold increase in PK-C activity while cells exposed to TPA for 48 h lost all PK-C activity. The changes in PK-C activity in TPA + RA-treated cells were accompanied by Ca2+/phospholipid(PL)-dependent phosphorylation in vitro of pp38 which is characteristic of treatment with RA alone, as well as the Ca2+/PL independent phosphorylation in vitro of pp82 and pp130 (vinculin) which is prevalent in cells treated continuously with TPA alone and is absent in RA treated cells. These results indicate that the macrophage phenotype induced by TPA + RA is similar to that produced by continuous exposure to TPA alone with respect to their in vitro phosphoprotein patterns, cytochemical markers, cell adherence and morphology, but that the disappearance of PK-C is not an obligatory characteristic of these cells. PMID- 3099100 TI - [Zinc in the seminal plasma in infertile men]. AB - Zinc, acid phosphatase and fructose in seminal fluid as well as FSH and LH in serum were determined in 223 men who were examined because of conjugal infertility. The concentrations of zinc, fructose and acid phosphatase in the seminal fluid of patients with normozoospermia (zinc 2.02 nmol/L; fructose 12.65 nmol/L; acid phosphatase 534063.49 U/L, oligozoospermia (zinc 2.09 nmol/L; fructose 12.79 nmol/L; acid phosphatase 553390.24 U/L) and azoospermia (zinc 2.10 nmol/L; fructose 12.56 nmol/L; acid phosphatase 599137.93 U/L) do not differ essentially. The average concentrations of zinc and acid phosphatase in the seminal fluid of patients with azoospermia and high concentrations of FSH and LH were significantly larger (zinc 2.58 nmol/L; acid phosphatase 683500.0 U/L) than those in patients with azoospermia and normal concentrations of FSH and LH (zinc 1.61 nmol/L; acid phosphatase 508750.0 U/L). In patients with normal gonadotropin levels, extremely low fructose concentrations in seminal plasma and congenital aplasia of seminal ducts, the concentrations of zinc in seminal plasma were enormously high. PMID- 3099099 TI - T-cell involvement in benign phase chronic myelogenous leukemia. AB - T cells from the peripheral blood of patients with chronic myeloid leukemia (CML) were cultured with phytohemagglutinin and T-cell growth factor (TCGF) in agar culture. These T-cell colonies were pooled and expanded further in liquid culture with TCGF and then simultaneously analysed for the E-rosette receptor with the monoclonal antibody OKT11 and for the presence of the Philadelphia (Ph1) chromosome. OKT11 analysis showed these populations to be composed 99.5% or more of T cells. In four of the seven patients the T-cell suspension showed 7/50 (14%), 3/36 (8%), 2/34 (6%), and 4/44 (9%) Ph1 metaphases. Furthermore, Ph1 metaphases were demonstrated in T-cell cultures in two patients when bone marrow metaphases simultaneously showed 90 and 100% Ph1 negative metaphases secondary to human leukocyte interferon therapy or combination chemotherapy. A minority of T cells in benign phase CML have the Ph1 abnormality despite reduced number of Ph1 metaphases in bone marrow from therapy. PMID- 3099101 TI - Long term care: legislation on abuse, neglect and exploitation of the elderly. PMID- 3099102 TI - Interleukin 2 receptors and responsiveness to recombinant human interleukin 2 in patients with systemic lupus erythematosus. AB - Defects in interleukin 2 (IL2) responsiveness may contribute to immunologic abnormalities in systemic lupus erythematosus (SLE). We studied the acquisition of IL2 receptors and responsiveness to recombinant human IL2 (rIL2) in the peripheral blood mononuclear cells (PBM) of patients with SLE and matched control subjects. Peak rIL2-induced proliferation was significantly decreased (mean reduction of 58%) in 5 of the 10 patients with SLE. Five of six patients with SLE studied for phytohemagglutinin-induced IL2 receptors had acquisition of IL2 receptors comparable to that of the control subjects. Some patients with SLE have a defect in rIL2-induced proliferation of their "resting" PBM that seems unrelated to a concomitant defect in phytohemagglutinin-induced IL2 receptor acquisition. This finding suggests that the defect in rIL2-induced proliferation may be due to either an abnormality in postreceptor signaling or an impairment in induction of high-affinity IL2 receptors. PMID- 3099103 TI - Focal cerebral ischemia: pathophysiologic mechanisms and rationale for future avenues of treatment. AB - Although approximately 500,000 patients suffer from a stroke each year in the United States, treatment of these patients to date has consisted primarily of prevention, supportive measures, and rehabilitation. The modification of experimental cerebral infarction by new pharmacologic agents, along with encouraging results from the restoration of blood flow to areas of focal ischemia in both laboratory and clinical trials, suggests that a more aggressive approach might be considered in selected patients with acute stroke. PMID- 3099104 TI - Mechanisms of age-related decline in antigen-specific T cell proliferative response: IL-2 receptor expression and recombinant IL-2 induced proliferative response of purified Tac-positive T cells. AB - Proliferative response of T cells from aged persons was significantly reduced to a specific antigen tuberculin-active peptide (TAP) determined by [3H]TdR uptake and FCM in comparison to that from the young. Cytokinetic analysis for the proliferative response to TAP showed that, in the aged, the clonal size or the number of the first generation responding cells to TAP was not significantly reduced but the ability to repeat replication was more profoundly affected. Neither the delayed entry into the cell replication nor prolongation of the cell cycle time could explain these results. Similar results have been reported on the proliferative response of T cells to mitogen: PHA (Phytohemagglutinin). Expression of Tac-antigen on T cells determined by anti-Tac antibody binding with FACS after stimulation with either TAP or PHA was found to be reduced significantly in the aged. Both the numbers of high and low affinity IL-2 receptors determined by radiolabelled IL-2 binding assay were also reduced in the aged, but the degree of reduction in number of high affinity ones was more pronounced than that in low affinity ones. Tac-positive T cells were isolated with the use of anti-Tac rosette methods and stimulated with recombinant IL-2 (r IL-2). Their proliferative response was significantly lower in the aged than that in the young at any concentration of r-IL-2 examined. The number of the first generation responding cells to r-IL-2 in purified Tac-positive T cells from the aged was 82% of that from the young whereas the proliferative response by aged T cells was 39% of that by young ones when the cells were allowed to repeat replication for 3 days. The mechanisms of these multifactorial defects in proliferation of T cells from aged persons were discussed. PMID- 3099105 TI - The financial burden of medical care expenses for children. AB - Data from the 1980 National Medical Care Utilization and Expenditure Survey are used to assess whether financial burdens incurred in obtaining medical services for children are distributed equitably among families with different incomes. When measured in absolute terms, out-of-pocket charges appear to increase in a progressive fashion with family income. However, when out-of-pocket charges are measured relative to ability to pay, a regressive pattern is demonstrated. Within the poverty population, children with continuous Medicaid coverage have much lower out-of-pocket costs than other children. Extension of Medicaid coverage to additional children below poverty is suggested as one approach toward reducing current inequities. PMID- 3099106 TI - Case-mix differences between hospital-based and freestanding skilled nursing facilities. A review of the evidence. AB - Many health care services are available in both hospital and freestanding settings. Hospital-based providers are usually much more expensive than freestanding providers. According to Medicare data, costs in hospital-based skilled nursing facilities (SNFs) are twice those of freestanding facilities. While critics charge that this is the result of inefficiency, hospitals counter that higher costs are caused by treatment of sicker patients and provision of higher-quality care. This paper analyzes the research on the case-mix differences between hospital-based and freestanding SNFs. On the basis of this analysis, it appears that hospital-based facilities tend to serve more severely ill patients (i.e., have a more difficult case mix) than do freestanding facilities. Case-mix differences, however, appear to explain less than half of the cost differential between the two types of facilities. PMID- 3099107 TI - [Physiopathologic considerations on light-chain deposition disease]. PMID- 3099108 TI - [Nephropathy caused by deposition of monoclonal light chains. Presentation of 4 cases]. PMID- 3099109 TI - [Modulation of the expression of histocompatibility antigens in thyroid follicular cells and in the beta cells of the pancreas: implications in the pathogenesis of thyroid autoimmune diseases and type 1 diabetes mellitus]. PMID- 3099110 TI - [Prevalence of monoclonal gammapathy in the La Cabrera Province]. PMID- 3099111 TI - Influence of pertussis toxin on the effects of guanine nucleotide on adenylate cyclase in rat striatal membranes. AB - The influence of pertussis toxin on the effects of guanine nucleotide on adenylate cyclase activity were investigated in rat striatal membranes. GTP promoted and inhibited the activity at 1 and 100 microM, respectively. The inhibitory effects of GTP were abolished by pretreatment of the membranes with pertussis toxin. GppNHp (guanyl-5'-y1-beta,gamma-imidodiphosphate) exerted only stimulatory effects and pertussis toxin did not affect the effects of GppNHp. GDP at 10 and 100 microM caused significant inhibition which was completely suppressed by pertussis toxin. It is suggested that guanine nucleotide regulates the affinity of as in stimulatory GTP-binding regulatory protein to either beta gamma or catalytic units of adenylate cyclase in a flip-flop manner. Inhibitory GTP-binding regulatory protein seems to play a regulatory role in inhibiting alpha s activity supplying the beta gamma heterodimer. PMID- 3099112 TI - Ascorbic acid enhances the release of luteinizing hormone-releasing hormone from the mediobasal hypothalamus in vitro. AB - Ascorbic acid is frequently used in in vitro studies of neurotransmitter-evoked release of luteinizing hormone-releasing hormone (LHRH) from hypothalamic fragments. Although it is assumed that ascorbate merely prevents the oxidative degradation of catecholamines, we have discovered that ascorbic acid itself produces significant increases in the release of LHRH. Our studies showed that ascorbic acid, at concentrations below 1 mM, produced a dose-dependent release of LHRH from incubated rat mediobasal hypothalamus (MBH). The magnitude of the ascorbate-induced release was in the range of 100-200% above controls; significant amounts of LHRH were released only if the MBH were incubated with ascorbate for time periods longer than 30 minutes. We also found that ascorbate induced increases in LHRH were equivalent to those produced by another LHRH secretagogue, naloxone, and that the combined effects of the two substances were additive in nature. Although the mechanisms underlying this effect are not fully understood, nonspecific chemical reduction is probably not a factor since sodium metabisulfite did not induce the release of LHRH. It seems probable that ascorbate may enhance the activity of endogenous norepinephrine in the MBH and, thereby, lead to increased release of LHRH. PMID- 3099113 TI - Evidence for thyrotropin-releasing hormone (TRH) biosynthesis in rat prostate. AB - TRH occurs in very high concentration in rat prostate. A species specific protein with repetitive -Gln-His-Pro-Gly- sequences, which are flanked on the N- and C terminus by paired basic residues, has been shown to be the source of TRH in frog skin and rat hypothalamus. Following cleavage by trypsin-like enzymes, the peptide fragments with N-terminal Gln spontaneously cyclize to pGlu while Gly within the C-terminally extended peptides serves as the -NH2 donor for the alpha amidation of the proline residue. Because this last step in the biosynthesis of TRH is rate limiting for pGlu-His-Pro-Gly, we have combined several chromatographic and radioimmunoassay techniques to identify this TRH precursor in rat prostate. PMID- 3099114 TI - Transfer of arachidonate from phosphatidylcholine to phosphatidylethanolamine and triacylglycerol in guinea pig alveolar macrophages. AB - Guinea pig alveolar macrophages were labeled by incubation with either arachidonate or linoleate. Arachidonate labeled phosphatidylcholine (PC), phosphatidylethanolamine (PE) and triglycerides (TG) equally well, with each lipid containing about 30% of total cellular radioactivity. In comparison to arachidonate, linoleate was recovered significantly less in PE (7%) and more in TG (47%). To investigate whether redistributions of acyl chains among lipid classes took place, the macrophages were incubated with 1-acyl-2-[1 14C]arachidonoyl PC or 1-acyl-2-[1-14C]linoleoyl PC. After harvesting, the cells incubated with 1-acyl-2-[1-14C]linoleoyl PC contained 86% of the recovered cellular radioactivity in PC, with only small amounts of label being transferred to PE and TG (3 and 6%, respectively). More extensive redistributions were observed with arachidonate-labeled PC. In this case, only 60% of cellular radioactivity was still associated with PC, while 22 and 12%, respectively, had been transferred to PE and TG. Arachidonate transfer from PC to PE was unaffected by an excess of free arachidonate which inhibited this transfer to TG for over 90%, indicating that different mechanisms or arachidonoyl CoA pools were involved in the transfer of arachidonate from PC to PE and TG. Cells prelabeled with 1 acyl-2-[1-14C]arachidonoyl PC released 14C-label into the medium upon further incubation. This release was slightly stimulated by zymosan and threefold higher in the presence of the Ca2+-ionophore A23187. Labeling of macrophages with intact phospholipid molecules appears to be a suitable method for studying acyl chain redistribution and release reactions. PMID- 3099115 TI - Regulation of liver cell ganglioside composition by extracellular fluid viscosity. AB - The viscosity of plasma and extracellular fluid has been shown to be a regulator of lipoprotein production both in cultured hepatocytes and in vivo. The possibility that this extracellular effect on cell function involves modulation of cell surface membrane components was examined. In the present work, we studied the effect of medium viscosity on liver cell gangliosides known to be involved in various membrane functions and to be located predominantly at the cell surface membrane. Cultivation of isolated hepatocytes as primary cultures markedly reduced the ganglioside content, but this reduction process was attenuated by increasing the viscosity of the culture medium. Elevation of extracellular fluid viscosity inhibited the degradation of the cell gangliosides and secretion of lysosomal enzymes involved in ganglioside degradation. The cellular activity of these enzymes as well as the activity of enzymes involved in ganglioside synthesis, CMP-NANA:GM1 sialyltransferase, CMP-NANAP:GM3 sialyltransferase and UDP-galactose:GD2 galactosyltransferase, were not affected by modulation of the extracellular medium viscosity. It is proposed that the modulation of cell ganglioside content by extracellular fluid viscosity is due to an effect on enzymes involved in ganglioside catabolism. PMID- 3099117 TI - [Arterial blood gas analysis during a rapid sequence induction procedure]. PMID- 3099116 TI - Glucosylceramide and the level of the glucosidase-stimulating proteins. AB - The concentration of beta-glucosidase-stimulating proteins (called cohydrolase here) was measured in mouse liver and brain by immunoassay. Factors that might influence the levels of cohydrolase were examined. Injecting mice with an inactivator of glucosidase (conduritol B epoxide) rapidly produced elevations in liver glucosylceramide (the enzyme's substrate) and in liver and brain cohydrolase. Injection of glucosylceramide emulsified with Myrj 52 produced the same two effects in liver but not in brain. The increases in cohydrolase level induced by the enzyme inhibitor persisted in both organs for at least seven days, reaching 61-70% above the normal level. Injection of emulsified galactocerebroside, sphingomyelin and mixed glucosphingolipids but not of ceramide also produced rises in cohydrolase level. An increase in cohydrolase level resulted from injection of phenylhydrazine, which produces hemolysis and consequently an increased workload for the glucosidase of liver. When the enzyme inhibitor and/or larger amounts of glucosylceramide emulsion were injected (750 mg/kg body weight), increases in liver weight of 13 to 37% appeared within one day. The increased weight was characterized by increases in the weights of protein, total lipid and DNA and a very high increase in glucosylceramide level. These procedures have produced a rapidly developing model version of Gaucher disease in mice. Injected glucocerebroside also induced an elevated level of glucosidase activity. PMID- 3099118 TI - [Prognostication of individual radiation sensitivity of animals, based on the use of a mathematical method of object classification]. AB - A statistical method of object classification based on the use of linear discriminant analysis, was employed to solve the problem of prediction of the outcome of acute radiation disease. In experiments on 23 monkeys irradiated at a dose of 5.3 Gy 14 animals had survived and 9 perished. The initial state and early response (in 5 h) to gamma-beam radiation were assessed. The total number of the analyzed parameters was 16. According to the experimental results an integral index--discriminator--was computed for each object. Values for the survivors ranged within 136.1-151.3, and for 9 more radiosensitive animals the values of discriminators turned out to be higher (151.9-168.7). The procedure of prognosis was the following. 23 monkeys were randomly divided into 2 groups (using the table of random numbers). The 1st group (a study sample) included 13 animals, of them 8 survived and 5 perished. The 2nd group (a control predictor sample) included 10 animals, of them 6 survived and 4 perished by the end of the experiment. The authors described 3 variants of a random selection of the animals both for the 1st and 2nd groups. The results of prognosis were compared with the experimental results. Erroneous prognosis for each variant was 10, 0 and 20%, respectively. PMID- 3099119 TI - [Endocrine status in the prognostication of individual radiation sensitivity]. AB - Experiments on rats dogs and monkeys demonstrated a high prognostic value of the direct adrenocortical activity index--the level of glucocorticoids in the blood (the accuracy of prognosis was 80-85%). The employment of overall comprehensive evaluation of the endocrine status for a number of indices to predict individual radiosensitivity was shown to hold promise. PMID- 3099120 TI - [Diagnosis and prevention of diabetes mellitus]. PMID- 3099121 TI - [Morbidity of schistosomiasis in Brazil. IV--Course in treated patients and their controls]. AB - A comparative study on the evolutive morbidity of schistosomiasis mansoni in treated and non-treated patients in an endemic area was carried-out with evaluation of the treatment after one and six years. In the first year after treatment there was both an improvement in the clinical conditions and a dramatic reduction in the number of S. mansoni eggs eliminated by the treated patients in relation to the controls. However, after six years of observations, although the number of S. mansoni eggs eliminated by the treated patients was still less than in the control group, it was nearly the same number as before treatment. In both treated and non-treated groups there was an increase in the severity of the clinical forms of schistosomiasis, with a certain tendency of greater severity in the control group. Therefore the authors recommend that the specific treatment of the population in endemic area should be done at intervals of two to three years, and that the treatment should be associated to the environmental sanitation, water supply and the education of the population. PMID- 3099122 TI - [Experimental behavior of samples of Schistosoma mansoni in relation to clinical forms of schistosomiasis. I--Study in mice]. AB - Twenty isolates of Schistosoma mansoni were obtained from patients, all males 13 to 30 years old, autochtonous from the Village of Capitao Andrade, municipality of Itanhomi, state of Minas Gerais, where an evolutive study of Mansoni's schistosomiasis is being performed since 1973. The isolates came from six patients with schistosome-infections (type I), six with the hepato-intestinal form (type II), and eight with the hepatosplenic form (type III). Each isolate was inoculated in mice divided in three groups of 16, exposed to 25, 50 and 100 cercariae, respectively. Controls were 12 uninfected mice. After 90 days adult worms were recovered from the portal by perfusion, from four mice of each experimental groups. Mice dying at various intervals and half of the rest f mice in each group sacrificed on the 90th and the 180th days were studied according to the following parameters: weight of liver, spleen, lung and intestine; egg count in the small intestine (proximal and medial) and large intestine (distal). The average numbers of worms obtained by perfusion from groups I, II and III were 21.9%, 22% and 17.8% respectively. The average natural mortality rates of mice submitted to infection with 25, 50 and 100 cercariae were, respectively, 12.4%, 23.2% and 40.2% for group I, 4.7%, 19.5% and 22.2% for group II and 11.4%, 29.5% and 41.6% for group III, being therefore proportional to the inocula.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099124 TI - Metabolic efficacy of enteral feeding in malnourished cancer and noncancer patients. AB - Total parenteral nutrition and enteral nutrition are the two available methods for supplementary nutritional support of malnourished patients. Although supplemental alimentation is beneficial in malnourished patients, it is unclear whether malnourished cancer bearing patients are successfully replenished with similar nutritional support. We studied the efficacy of 2 weeks of enteral nutrition on intermediary glucose and protein metabolism in malnourished tumor bearing (TB) and non-tumor bearing (NTB) patients. Both TB and NTB patients showed equivalent suppression of endogenous glucose production (2.13 +/- 0.23 to 0.35 +/- 0.16 mg/kg/min and 2.35 +/- 0.18 to 0 mg/kg/min), suppression of alanine to glucose conversion (43.8 +/- 10.6% to 0.75 +/- 0.41% and 37.0 +/- 10.7% to 0.11 +/- 0.09%), attainment of positive nitrogen balance (-2.15 +/- 1.18 to 4.26 +/- 1.37 gN/d and -2.25 +/- 0.63 to 4.32 +/- 0.44 gN/d) and suppression of protein catabolism (2.39 +/- 0.13 to 1.10 +/- 0.27 gP/kg/d and 2.23 +/- 0.04 to 1.34 +/- 0.22 gP/kg/d). Following 2 weeks of enteral support, the TB patients differed from the NTB group with significantly elevated lactate levels (80 +/- 8 v 48 +/- 7 mg/L) and depressed plasma glycine levels (264 +/- 12 v 356 +/- 27 mumol/L plasma) and inability to replenish fat stores (triceps skin fold, 7.6 +/- 1.5 to 7.1 +/- 1.5 mm in TB v 5.9 +/- 0.7 to 8.0 +/- 1.2 mm in NTB). A significant reduction in whole body protein synthesis (2.08 +/- 0.19 to 1.84 +/- 0.18 gP/kg/d) in TB patients was obtained while NTB showed no significant change (1.86 +/- 1.3 to 1.91 +/- 0.26 gP/kg/d).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099123 TI - Increased gonadotropin responsiveness to gonadotropin-releasing hormone during fasting in normal subjects. AB - To investigate whether food deprivation affects hormone release from pituitary gonadotrophs, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses to intravenous (IV) administration of 50 micrograms gonadotropin releasing hormone (GnRH) were determined in 12 healthy subjects (six women and six men) after an overnight fast and after a fasting period of 56 hours. In the female participants, these GnRH tests were performed early in the follicular phase of the menstrual cycle. Blood glucose declined during the fast from 4.4 +/- 0.1 (mean +/- SEM) to 3.3 +/- 0.1 mmol/L (P less than .001). LH and FSH responsiveness to GnRH--as reflected by hormone incremental areas--increased from 1973 +/- 256 to 3267 +/- 450 (IU/L X min) for LH (P less than .001), and from 376 +/- 44 to 705 +/- 112 (IU/L X min) for FSH (P less than .01). When control studies were carried out in nonfasted subjects in exactly the same way as in the fasted participants, the gonadotropin responsiveness to GnRH did not change significantly between the tests. To explore possible mechanisms behind the increased gonadotropin responsiveness in fasted subjects, six of the above mentioned healthy women were given nine small oral doses of glucose (each dose 0.5 g/kg) during an additional 56-hour fast to prevent blood glucose from falling significantly during the period of food deprivation. This did not change the hormone response pattern at all, since both the LH and the FSH responses to GnRH increased significantly during the glucose-supplemented fasting period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099125 TI - Sequential alterations in glomerular prostaglandin and thromboxane synthesis in diabetic rats: relationship to the hyperfiltration of early diabetes. AB - The present study examined the role of enhanced production of prostaglandin (PG) E2 and 6-keto-PGF1a, the stable metabolite of PGI2, by glomeruli from streptozotocin diabetic rats in the mediation of hyperfiltration. Correlative measurements of insulin clearance (CIn) and glomerular production of PGE2, 6-keto PGF1a and thromboxane (TX) B2 (the stable metabolite of TXA2) were made at two time points, nine to 15 days and 25 to 28 days after streptozotocin. CIn was elevated by 40% to 50% in diabetic rats studied at nine to 15 or 25 to 28 days compared to values in age-matched controls. Basal production of PGE2, 6-keto PGF1a and TXA2 (as reflected by TXB2) and increases in response to A23187 were elevated in glomeruli from nine to 15-day diabetic rats compared to values in control glomeruli. Exogenous arachidonate abolished these differences. Treatment of nine-day diabetic rats with indomethacin (3 mg/kg/d) rapidly (within 24 hours) and reversibly suppressed CIn without altering CIn in control rats. Indomethacin had no effect on plasma glucose in control or diabetic rats. Treatment of nine to 15-day diabetic rats with insulin (10 U/kg/d by osmotic minipump) beginning 24 hours after streptozotocin lowered plasma glucose to values that were not significantly different from control and prevented the rise in CIn. Treatment of diabetic rats with insulin or incubation of glomeruli from untreated diabetic rats with insulin (0.3 mU/mL) for two hours in vitro reduced basal and A23187 induced increases in PGE2, 6-keto PGF1a, and TXB2 to values that were not different from those in control glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099128 TI - Serum IgG, IgM, and C3 levels in Schistosoma japonicum infected rabbits. AB - New Zealand white rabbits were infected with 250 or 500 Schistosoma japonicum cercariae of Philippine-Leyte strain. Following the initial pre-infection bleed, blood was collected 2, 4, 6, 8, 11, 14, 17, 20, 23, 26, 29, and 32 weeks post infection, and IgG, IgM, and C3 levels were assayed in the serum samples by single radial immunodiffusion. IgG and IgM achieved peak levels at 14 weeks post infection and began to decrease in concentration by 26 weeks. At 32 weeks, some of the infected rabbits exhibited significantly reduced IgG and IgM levels which approached the concentrations assayed in the control animals. The infected animals demonstrated significantly elevated C3 levels (p less than or equal to 0.001) during the 6th to 26th weeks post-infection, with the exception of the 20th week. PMID- 3099126 TI - Cloning in Escherichia coli of a Bacillus subtilis arginine repressor gene through its ability to confer structural stability on a fragment carrying genes of arginine biosynthesis. AB - The structural stability of a previously isolated recombinant plasmid pUL720 was examined. pUL720 contains an insert in pBR322 of 23.8 kbp comprising 4 EcoR1 fragments of sizes 12 kbp and 6 kbp, both of which are homologous to the B. subtilis genome, and 5 kbp and 0.8 kbp (of unknown origin). The 12 kbp fragment, which encodes the arginine biosynthesis genes argA-F-cpa, cannot be cloned in isolation in a high copy vector in E. coli but can be inserted into a low copy vector pGV1106 to generate pUL800. Deletion analysis of pUL720 indicated that the 5 kbp and 0.8 kbp fragments were not necessary to maintain plasmid stability. The 6 kbp fragment, when cloned into the EcoR1 site in pACYC184 to generate pUL2030, permitted the cloning in trans in pBR322 of the 12 kbp fragment or subclones containing the instability region. The minimum inhibitory concentration of kanamycin determined in the B. subtilis argC-neo transcriptional fusion pUL730 and expression of the argF gene product, ornithine carbamoyltransferase (OCTase), in pUL800 were reduced by approximately 3 and 2 fold respectively under conditions of arginine excess and in the presence of pUL2030. B. subtilis partial diploids were constructed by transforming parental and arginine hydroxamate resistant (Ahr) mutants with pUL2100, a plasmid generated by inserting the 6 kbp fragment into the integration vector pJH101. The 6 kbp fragment complemented and restored parental type levels of OCTase in ahrC mutants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099129 TI - Streptococcus mutans ribosomal preparations: purification and properties. AB - Ribosomal preparations were obtained from Streptococcus mutans. Sucrose density gradient analyses showed the ribosomes to be 70S and dissociated subunits to be 56S and 34S. The ribosomal preparation contained 57.4% RNA and 42.6% protein and gave an absorption maximum at 260 nm and a minimum at 235 nm and ribosomal particles were approximately 150-180 X 190-220 A as determined by electron microscopy. Immunodiffusion analysis of pooled antiserum raised by injecting the ribosomal preparation into rabbits disclosed precipitin lines with glucosyltransferase and lipoteichoic acid preparations from S. mutans. Gas chromatography showed rhamnose and glucose to be present in the ribosomal preparation indicating the presence of nonribosomal carbohydrate materials. The ribosomes were able to synthesize precipitable polypeptides when exogenous mRNA and tRNA were added and anti-ribosomal antibodies reduced this activity. Protease treatment rendered the ribosomal preparation less immunogenic in rats and less antigenic when the ribosomal preparation was used to coat erythrocytes for passive haemagglutination assays, while RNase treatment of the ribosomal preparation had no effect, suggesting that a protein(s) is the principal immunogenic moiety of the ribosomal antigen. Polyacrylamide gel electrophoresis of the ribosomal preparation revealed 27 protein bands of which five were found to react with hyperimmune rabbit antisera to the S. mutans ribosomal preparation by Western blot analysis. Washing the ribosomal preparation with 1 M NH4Cl did not remove any of the five immunogenic ribosomal protein antigens indicating that these were innate ribosomal proteins. PMID- 3099127 TI - The effect of spo0 mutations on the expression of spo0A- and spo0F-lacZ fusions. AB - We have constructed spo0A-lacZ and spo0F-lacZ fusions with a temperate phage vector and have investigated how spo0 gene products are involved in the expression of each of these genes. The expression of spo0A-lacZ and spo0F-lacZ was stimulated at about the time of cessation of vegetative growth in Spo+ cells. This stimulation of spo0A-lacZ was impaired by mutations in the spo0B, D, E, F or H genes but was not affected by mutations in the spo0J or K genes. Similar results were obtained with the spo0F-lacZ fusion. The effect of the spo0A mutation on spo0A-lacZ expression was characteristic: the spo0A-directed beta galactosidase activity found during vegetative growth was significantly enhanced in the spo0A mutant. This result suggests that spo0A gene expression is auto regulated being repressed by its own gene product. Another remarkable observation was the effect of the sof-1 mutation, which is known to be a spo0A allele; it suppressed the sporulation deficiency of spo0B, spo0D and spo0F mutants. The spo0A-lacZ stimulation, which is impaired by any one of these spo0 mutations, was restored by the additional sof-1 mutation. PMID- 3099130 TI - Resistance to metals by Pseudomonas aeruginosa clinical isolates. AB - The susceptibility of 326 clinical isolates of Pseudomonas aeruginosa to four metals was determined by agar dilution tests. Metal resistance was shown by 36% of the total isolates. The frequencies of resistance to individual ions were: mercuric, 31%; tellurite, 12%; arsenate, 10%; and chromate, 3%. The most frequent pattern was that of resistance to mercuric ions alone followed by mercury resistance associated with either tellurite, arsenate, or both. Resistance to more than one metal was found in 44% of metal-resistant isolates. The resistance to antibiotics was more frequent among metal-resistant isolates that in metal sensitive isolates. PMID- 3099131 TI - Induction of human interferon-gamma mRNA analyzed by cytoplasmic dot hybridization: effect of Con A, TPA, and A23187. AB - The cytoplasmic dot hybridization method was improved by eliminating non-specific false signals. The non-specific binding to a probe disappeared almost completely when the hybridized nitrocellulose sheet was treated with pronase. Using this improved method we demonstrated that reagents such as 12-O-tetradecanoylphorbol 13-acetate (TPA), concanavalin A (Con A) and a calcium ionophore (A23187) could induce the expression of IFN-gamma gene of a human T-lymphoblastoid cell line, TCL-Fuj 2M, where TPA functioned synergistically with Con A and A23187. However, when the cells were cultured with the ionophore for more than one day the amount of IFN-gamma mRNA was markedly reduced to a low level. PMID- 3099132 TI - Use of protein A in the serum-in-agar diffusion method in immune electron microscopy for detection of virus particles in cell culture. AB - A modified technique using protein A in the serum-in-agar (SIA) method for immune electron microscopy (IEM) was presented. Grids coated with staphylococcal protein A were floated on samples mounted on agar containing 2% antiserum and incubated at 37 C, for 60 min. After washing and staining, the grids were observed in an electron microscope. The effects of protein A on virus detection were evaluated using poliovirus and bovine rotavirus infected cell culture fluids. The results showed that the technique using protein A (PA-SIA) had at least 10-fold higher sensitivity for virus detection than the original SIA. The optimal concentration of protein A was 1 to 10 micrograms/ml for coating the grids to trap virus particles. The PA-SIA method was also compared with immunosorbent electron microscopy (ISEM). The former showed higher or at least the same sensitivity and some advantages in detecting antigen-antibody reaction than the latter method. These results indicate that our PA-SIA method may be superior to other IEM techniques presented previously for the detection and identification of viruses. PMID- 3099133 TI - Effect of mannitol and glucose on the distribution and trypsin susceptibility of protein A of Staphylococcus aureus. AB - The biological activity and morphological distribution of protein A on the cell surface were studied in a medium containing an excess of either mannitol or glucose, which suppressed protein A production of Staphylococcus aureus, Cowan I strain. Preculture of the organisms in the presence of a sugar suppressed the expression of protein A, resulting in a decrease in the number of cells bound with antiferritin rabbit IgG molecules, which specifically indicate protein A distribution. The distribution pattern of protein A on the cell surface changed with glucose but not with mannitol. The two-layered ferritin distribution on the organism grown in the control medium was altered into a heavily labeled, thick and rough layer with glucose, suggesting the induction of a conformational change in the polypeptide chain forming protein A. This was positively supported by the increase in trypsin susceptibility of protein A. PMID- 3099134 TI - Structural changes in the nucleoid of Bacillus subtilis at low temperature. AB - The external shape of the nucleoid of Bacillus subtilis strain w23 was examined with a new electron microscopic technique, the rapid freezing and substitution fixation method. The nucleoid of the log and stationary phase cells was recognized as an area devoid of ribosomes and widely dispersed in the cytoplasm, which was different from that observed in OsO4-fixed cells. If the bacteria were exposed to low temperatures (0 to 10 C), the nucleoid showed a highly concentrated shape in the middle of the cytoplasm. These structural changes were observed only when the bacteria were maintained in a high-salt buffer. The results are discussed in relation to the membrane fluidity at low temperature. PMID- 3099135 TI - Comparison of cytoplasmic membrane antigens of a wild type of Micrococcus luteus (lysodeikticus) and its autolysis-defective mutant by immunodiffusion. PMID- 3099136 TI - Teratogenic drugs in pregnancy. PMID- 3099137 TI - Lead intoxication in paint removal workers on the Sydney Harbour Bridge. AB - Lead intoxication is far more prevalent than is recognized by those persons who are exposed to lead fumes and dust in industry, as the early symptoms of intoxication are subtle and non-specific. The levels of lead in blood are a poor reflection of lead stores in the body and their potential toxicity, but are used frequently as the only test for screening of lead intoxication. Chelation of lead with calcium-EDTA is a more sensitive test to detect those persons who are at risk of toxicity. Industrial workers who are exposed regularly to lead must be screened on a periodic basis and a diagnosis of lead poisoning must be considered if substantial morbidity is to be avoided. We report six cases of men with significant lead intoxication who were employed on the Sydney Harbour Bridge, all of whom have benefited symptomatically from calcium-EDTA chelation therapy. PMID- 3099138 TI - Vitamin use in clinical medicine. PMID- 3099139 TI - Local percutaneous nitroglycerine therapy for "burning feet" syndrome. PMID- 3099140 TI - Lead intoxication in industry. PMID- 3099141 TI - Domiciliary oxygen: the cost-benefit dilemma. PMID- 3099142 TI - Domiciliary oxygen: rationalization of supply in the Hunter region from 1982 1986. AB - In October 1982, a clinic was planned at The Royal Newcastle Hospital to review the usage of domiciliary oxygen that was funded by the Provision of Aids for Disabled Persons scheme in the Hunter Region of New South Wales. Patient review included an assessment of the indications for domiciliary oxygen, education in the use of oxygen, the efficiency of delivery arrangements and the transfer from cylinders to concentrators as indicated. Between January and June 1983, 111 patients who were receiving oxygen at home were reviewed: 84 (76%) of these patients had chronic obstructive pulmonary disease; their two-year survival was 80% (95% confidence interval, 69%-87%) and five-year survival was 36% (95% confidence interval, 25%-46%). In 66 (59%) patients, review led to a reduction in the usage of domiciliary oxygen which was estimated to save $40,000 each year in the Hunter Region. In the year from 1985-1986 the decrease in the usage of oxygen at home represented an actual cost saving of $60,000 for the region ($470 per person) which translated into a saving of $95,000 ($740 per person) when inflation was taken into account. If our experience is projected nation-wide, the potential exists for a considerable cost saving by means of programmes to rationalize the use of domiciliary oxygen. PMID- 3099143 TI - Recent developments in nitrate therapy of ischaemic heart disease. PMID- 3099144 TI - Measurement of total-body oxygen, nitrogen, and carbon in vivo by photon activation analysis. AB - A method has been developed to measure total-body oxygen, nitrogen, and carbon in vivo using the x-ray beam of a 45-MV betatron and a whole-body counter. Following x-ray irradiation of living tissue, the positron emitting activation products 15O, 11C, and 13N are produced. The decay of these radionuclides has been measured in both phantoms and animals, and a computer curve-fitting algorithm used to resolve the decay curve into separate contributions from 15O, 11C, and 13N. The decay curve was corrected for interfering activity from 30P, 38K, and 34mCl, and in the case of live animals, also corrected for a substantial fraction of 11C lost through exhalation. Activation uniformity profiles have been measured for phantoms up to 30 cm in thickness. With a radiation dose of 20 cGy, total body O, N, and C were measured in dead rats with estimated accuracies of +/- 1.4%, +/- 4.5%, and +/- 1.5% [1 standard deviation (SD)], respectively. With a radiation dose of 40 cGy, total-body O, N, and C were measured in living rats with estimated accuracies of +/- 1.4%, +/- 6.9%, and +/- 1.5% (1 SD), respectively. It is anticipated that total-body O, N, and C similarly could be measured in human subjects with a radiation dose of 1-2 cGy and with accuracies comparable to those obtained in rats. Although most of the measurements were made using a beam energy of 45 MV, we have shown that useful results may be achievable with a beam energy as low as 25 MV. This accurate, convenient, and safe technique for total-body O, C, and N measurement should have applications in the study of nutritional status in health and disease, both in human subjects and in animals. PMID- 3099145 TI - A new description of the photon beam peak-depth profile as a function of field size. AB - The dose profile at peak depth in water is described as the product of an apparatus function and a source function. In principle, the source function is the circularly symmetric profile which would be measured at peak depth without any collimation. In practice, the peak-depth profile in the diagonal plane, measured for the largest collimator setting, is used for this purpose. The apparatus function represents the collimator acting upon the source function, and is referred to as the collimator function. The collimator function for any field size can be developed from the ratio of the peak-depth profile for a single medium-sized field and the source function. The method has been tested for a set of irregularly flattened 4-MV x-ray beams as well as for practically flat 15-MV x ray beams. The model requires as basic data only three peak-depth profiles: one in each principal plane of a medium-sized square field and the peak-depth profile in the diagonal plane for the largest field. It replaces the peak-depth transformation in the projective beam model. PMID- 3099146 TI - Determinations of Ngas and Prepl factors from commercially available parallel plate chambers: AAPM Task Group 21 protocol. AB - Using a Farmer chamber as a reference dosimeter, we have measured the Ngas (cavity-gas calibration factor) and Prepl (replacement correction factor) values for four parallel-plate chambers: a Holt chamber, a Capintec chamber, a Markus chamber, and an SHM chamber. Ngas determinations were done primarily using 60Co photons and nominal 18-MeV electrons for Ngas determinations. For Prepl determinations, we used nominal 18-, 15-, 12-, 9-, 6-, and 4-MeV electrons. PMID- 3099148 TI - [Endocrine function in anorexia nervosa occurring simultaneously in identical twins]. PMID- 3099147 TI - The MURCS association. Clinical, radiological, endocrinological and familial data in a 40-year old patient. PMID- 3099149 TI - Update: acquired immunodeficiency syndrome--United States. PMID- 3099150 TI - Salmonellosis at a resort hotel--Puerto Rico. PMID- 3099151 TI - Rabies prevention: supplementary statement on the preexposure use of human diploid cell rabies vaccine by the intradermal route. PMID- 3099152 TI - Multi-drug-resistant tuberculosis--North Carolina. PMID- 3099153 TI - Drinking and driving and binge drinking in selected states, 1982 and 1985--the Behavioral Risk Factor Surveys. PMID- 3099154 TI - Update on influenza activity in the United States, availability of influenza vaccines, and recommendations for the use of vaccines and amantadine. PMID- 3099155 TI - Compendium of animal rabies control, 1987. Prepared by: the National Association of State Public Health Veterinarians, Inc. PMID- 3099156 TI - Antibody response to A/Taiwan/86 (H1N1) virus in young adults receiving supplemental monovalent A/Taiwan/86 influenza vaccine following trivalent influenza vaccine. PMID- 3099157 TI - Infant mortality among black Americans. PMID- 3099158 TI - Increasing rate of Salmonella enteritidis infections in the Northeastern United States. PMID- 3099159 TI - Premature mortality in West Virginia, 1978-1982. PMID- 3099160 TI - Childbearing patterns among Puerto Rican Hispanics in New York City and Puerto Rico. PMID- 3099161 TI - Viral hepatitis--1984. PMID- 3099162 TI - [Study of metabolism in critically ill patients by indirect calorimetry]. AB - Indirect calorimetry was performed in 48 postsurgical critically ill patients including those with multiple organ failure. The patients were divided into two groups, organ failure group (OF group) and postsurgical control group (C group), according to the presence of postsurgical organ failure and severe infection. The following results were obtained. The ratio of energy expenditure to basal energy expenditure, reflecting a degree of hypermetabolism, was 1.44 +/- 0.38 in OF group and 1.26 +/- 0.23 in C group respectively. The change in respiratory quotient by caloric intake was greater in OF group than in C group, indicating that it is more important to maintain an adequate intake for the prevention of increased respiratory work and excess lipogenesis in OF group. When nitrogen intake as amino acids was sufficient (0.1-0.2 g/kg/day), nitrogen balance could be maintained around 0 by a caloric intake being equal to measured energy expenditure. A positive correlation was observed between arterial ketone body ratio reflecting energy charge in hepatocytes and respiratory quotient, indicating that in patients with impaired mitochondrial function in hepatocytes as shown by a decrease in ketone body ratio, glucose cannot be utilized effectively. These results let us conclude that calorimetry is indispensable in the management of critically ill patients and that adequate energy intake should be cautiously determined according to the calorimetry. PMID- 3099163 TI - [Clinical study of protein and amino acids metabolism in surgical infection- significance of administration of branched chain amino acids]. AB - Anastomotic leakage and fistula of alimentary tract are accompanied by peritonitis because of exudation of contents in the digestive canal. In order to inquire about metabolism of protein and amino acids in surgical infection, this study was performed by the method of a time related cross-over trial, comparing high branched chain amino acids (BCAA) solution with low BCAA solution. The following results were obtained. When metabolism is physiologically compensated in infection, it was suggested that there appeared to be gluconeogenesis, ureagenesis and a liver disturbance accompanied in the early phase of sepsis. Administration of BCAA leads to an inhibition of muscle protein break down and a promotion of visceral protein synthesis in the case of severe infection. Administration of BCAA enriched amino acids solution have an important therapeutic measure under severe stressed condition and a significant role in medicine. PMID- 3099164 TI - Transient inhibition of DNA synthesis results in increased dihydrofolate reductase synthesis and subsequent increased DNA content per cell. AB - We examined the role that blockage of cells in the cell cycle may play in the stimulation of gene amplification and enhancement of drug resistance. We found that several different inhibitors of DNA synthesis, which were each able to block cells at the G1-S-phase boundary, induced an enhanced cycloheximide-sensitive synthesis of an early S-phase cell cycle-regulated enzyme, dihydrofolate reductase, and of other proteins as well. This response was specific, in that blockage at the G2 phase did not result in overproduction of the enzyme. When the cells were released from drug inhibition, DNA synthesis resumed, resulting in a cycloheximide-sensitive elevation in DNA content per cell. We speculate that the excess DNA synthesis (which could contribute to events detectable later as gene amplification) is a consequence of the accumulation of S-phase-specific proteins in the affected cells, which may then secondarily influence the pattern of DNA replication. PMID- 3099165 TI - Product of Saccharomyces cerevisiae nuclear gene PET494 activates translation of a specific mitochondrial mRNA. AB - The product of Saccharomyces cerevisiae nuclear gene PET494 is known to be required for a posttranscriptional step in the accumulation of one mitochondrial gene product, subunit III of cytochrome c oxidase (coxIII). Here we show that the PET494 protein probably acts in mitochondria by demonstrating that both a PET494 beta-galactosidase fusion protein and unmodified PET494 are specifically associated with mitochondria. To define the PET494 site of action, we isolated mutations that suppress a pet494 deletion. These mutations were rearrangements of the mitochondrial gene oxi2 that encodes coxIII. The suppressor oxi2 genes had acquired the 5'-flanking sequences of other mitochondrial genes and gave rise to oxi2 transcripts carrying the 5'-untranslated leaders of their mRNAs. These results demonstrate that in wild-type cells PET494 specifically promotes coxIII translation, probably by interacting with the 5'-untranslated leader of the oxi2 mRNA. PMID- 3099166 TI - Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene. AB - Monoclonal antibodies were prepared against a fraction of nuclear proteins of Drosophila melanogaster identified as tightly binding to DNA. Four of these antibodies were directed against a 19-kilodalton nuclear protein; immunofluorescence staining of the polytene chromosomes localized the antigen to the alpha, beta, and intercalary heterochromatic regions. Screening of a lambda gt11 cDNA expression library with one of the monoclonal antibodies identified a recombinant DNA phage clone that produced a fusion protein immunologically similar to the heterochromatin-associated protein. Polyclonal sera directed against the bacterial lacZ fusion protein recognized the same nuclear protein on Western blots. A full-length cDNA clone was isolated from a lambda gt10 library, and its DNA sequence was obtained. Analysis of the open reading frame revealed an 18,101-dalton protein encoded by this cDNA. Two overlapping genomic DNA clones were isolated from a Charon 4 library of D. melanogaster with the cDNA clone, and a restriction map was obtained. In situ hybridization with these probes indicated that the gene maps to a single chromosome location at 29A on the 2L chromosome. This general strategy should be effective for cloning the genes and identifying the genetic loci of chromosomal proteins which cannot be readily assayed by other means. PMID- 3099167 TI - RNA polymerase II interacts with the promoter region of the noninduced hsp70 gene in Drosophila melanogaster cells. AB - By using a protein-DNA cross-linking method (D. S. Gilmour and J. T. Lis, Mol. Cell. Biol. 5:2009-2018, 1985), we examined the in vivo distribution of RNA polymerase II on the hsp70 heat shock gene in Drosophila melanogaster Schneider line 2 cells. In heat shock-induced cells, a high level of RNA polymerase II was detected on the entire gene, while in noninduced cells, the RNA polymerase II was confined to the 5' end of the hsp70 gene, predominantly between nucleotides -12 and +65 relative to the start of transcription. This association of RNA polymerase II was apparent whether the cross-linking was performed by a 10-min UV irradiation of chilled cells with mercury vapor lamps or by a 40-microsecond irradiation of cells with a high-energy xenon flash lamp. We hypothesize that RNA polymerase II has access to, and a high affinity for, the promoter region of this gene before induction, and this poised RNA polymerase II may be critical in the mechanism of transcription activation. PMID- 3099168 TI - Specific activation of the cellular Harvey-ras oncogene in dimethylbenzanthracene induced mouse mammary tumors. AB - Genomic DNAs from dimethylbenzanthracene-induced BALB/c mouse mammary tumors arising from the transplantable hyperplastic outgrowth (HPO) line designated DI/UCD transformed NIH 3T3 cells upon transfection. Transforming activity was attributed to the presence of activated Harvey ras-1 oncogenes containing an A--- T transversion at the middle adenosine nucleotide in codon 61. DNAs from untreated DI/UCD HPO cells and radiation-induced and spontaneous mammary tumors from the DI/UCD HPO line failed to transform NIH 3T3 cells. The results indicated that the mutation activation of Harvey ras-1 oncogenes was specific to dimethylbenzanthracene treatment in the mouse mammary tumor system. PMID- 3099169 TI - Isolation and oncogenic potential of a novel human src-like gene. AB - We have isolated cDNA molecules representing the complete coding sequence of a new human gene which is a member of the src family of oncogenes. Nucleotide sequence analysis revealed that this gene, termed slk, encoded a 537-residue protein which was 86% identical to the chicken proto-oncogene product, p60c-src, over a stretch of 191 amino acids at its carboxy terminus. In contrast, only 6% amino acid homology was observed within the amino-terminal 82 amino acid residues of these two proteins. It was possible to activate slk as a transforming gene by substituting approximately two-thirds of the slk coding sequence for an analogous region of the v-fgr onc gene present in Gardner-Rasheed feline sarcoma virus. The resulting hybrid protein molecule expressed in transformed cells demonstrated protein kinase activity with specificity for tyrosine residues. PMID- 3099170 TI - Delimiting regulatory sequences of the Drosophila melanogaster Ddc gene. AB - We delimited sequences necessary for in vivo expression of the Drosophila melanogaster dopa decarboxylase gene Ddc. The expression of in vitro-altered genes was assayed following germ line integration via P-element vectors. Sequences between -209 and -24 were necessary for normally regulated expression, although genes lacking these sequences could be expressed at 10 to 50% of wild type levels at specific developmental times. These genes showed components of normal developmental expression, which suggests that they retain some regulatory elements. All Ddc genes lacking the normal immediate 5'-flanking sequences were grossly deficient in larval central nervous system expression. Thus, this upstream region must contain at least one element necessary for this expression. A mutated Ddc gene without a normal TATA boxlike sequence used the normal RNA start points, indicating that this sequences is not required for start point specificity. PMID- 3099171 TI - Drosophila chorion gene amplification requires an upstream region regulating s18 transcription. AB - A cluster of Drosophila melanogaster chorion genes at locus 66D on the third chromosome amplifies 60-fold in the ovarian follicle cells prior to the onset of gene expression. A 3.8-kilobase (kb) region of the gene cluster can induce tissue specific amplification in transformants. Previous models postulated that amplification is activated in follicle cells by transcription of one of the two chorion genes (s15 and s18) located within the 3.8-kb essential region. In this study, we showed that neither s15 nor s18 chorion gene transcription was required for amplification. However, a 510-bp region upstream from s18 contained sequences essential for both amplification and s18 transcription. No other region within the 3.8-kb fragment was required for amplification. We propose that upstream transcription control elements rather than transcription per se are involved in controlling amplification during development. PMID- 3099172 TI - DNA binding is not sufficient for nuclear localization of regulatory proteins in Saccharomyces cerevisiae. AB - We showed by immunofluorescence that the procaryotic DNA-binding protein LexA and a chimeric protein that contains the DNA-binding portion of LexA (amino acids 1 to 87) and a large portion (amino acids 74 to 881) of the Saccharomyces cerevisiae positive regulatory GAL4 protein (GAL4 gene product) are not preferentially localized in the nucleus in S. cerevisiae. PMID- 3099173 TI - A DNA damage-responsive Drosophila melanogaster gene is also induced by heat shock. AB - A gene isolated by screening Drosophila melanogaster tissue culture cells for DNA damage regulation was also found to be regulated by heat shock. After UV irradiation or heat shock, induction is at the transcriptional level and results in the accumulation of a 1.0-kilobase polyadenylated transcript. The restriction map of the clone bears no resemblance to the known heat shock genes, which are shown to be uninduced by UV irradiation. PMID- 3099174 TI - Rh antigen immunoreactivity after histidine modification. AB - 125I-anti-D IgG and unlabeled blood group allo-antisera in combination with 125I protein A were employed in assessing antibody binding to red cells (RBC) treated with histidine reagents. The acylating reagent diethylpyrocarbonate (DEP), the alkylating reagent p-bromophenacyl bromide (pBPB) and the photosensitizer dye Rose Bengal (RB) were used under conditions that usually result in the selective modification of histidine in isolated proteins. Progressive apparent inactivation of the D antigen in ghost membranes occurred with increasing DEP concns, which was not demonstrably reversible by hydroxylamine since this reagent itself inactivated the D antigen. Exposure of red cells to 5 mM p BPB resulted in a 50% decrease in binding of 125I-anti-D IgG. Photo-oxidation of RBC in the presence of Rose Bengal apparently inactivated all the major Rh antigens as detected either by labeled anti-D IgG binding, IgG agglutinating serological reagents, or the binding of 125I-labeled protein A following the sensitization of cells with unlabeled antisera. Under conditions of RB treatment, where hemolysis was absent or minimal, 125I anti-D IgG binding decreased to 38-49% of the level seen in controls. Rose Bengal treatment of R1r RBC revealed varying inactivation of all the Rh antigens, i.e. D 15%, C 89%, c 73%, e 54% inactivated, whereas antibody binding activity of the Fya and Fyb antigens present in the same cell was unaffected. Previous reports as well as the pH profile of anti-D binding have implicated the participation of histidine in Rh antigen expression. Our results are consistent with histidine involvement in Rh activity. Whether Rh antigens have essential histidine(s) involved directly in epitope structure, or instead depend on a critical histidine(s) at the lipid-protein interface that modulates antigen expression remains to be determined. PMID- 3099175 TI - Evidence for the binding of human serum amyloid P component to Clq and Fab gamma. AB - In order to clarify the mechanism of interaction of serum amyloid P component (SAP) with complement, the interaction of SAP with C1q and with IgG was studied. It is known that SAP binds Sepharose in the presence of calcium. When purified 125I-C1q was incubated with SAP prior to Sepharose affinity chromatography, 125I C1q was retained. However, in the absence of SAP, the 125I-C1q was not retained. To further examine the interaction of SAP with C1q, isolated SAP was incubated at varying ratios with C1q in the presence of 1.5 mM Ca2+. These mixtures were subsequently examined via crossed immunoelectrophoresis against goat anti-SAP. A change in the electrophoretic behavior of SAP was observed in the presence of C1q. In other studies, it was observed that SAP might interact with the collagen like stem of C1q. In these latter studies, 125I-SAP was incubated with pepsin digests of C1q in a microtitre solid-phase binding assay. In addition, a microtitre solid-phase binding assay was utilized in order to investigate the possible binding of isolated 125I-SAP with IgG. Interestingly in the presence of Ca2+, human IgG and Fab gamma, but not Fc gamma, were found to bind 125I-SAP. PMID- 3099176 TI - Immunoglobulin heavy chain associated protein in multiple sclerosis cerebrospinal fluid. AB - Immunoglobulins G, A, and M (IgG, IgA and IgM) were isolated from multiple sclerosis (MS) cerebrospinal fluid (CSF) and sera by Protein A-Sepharose (PAS) affinity chromatography or using solid-phase immunoabsorbents. An isoelectric point heterogeneous protein with apparent mol. wt of 74,000-80,000 was seen consistently when CSF Igs were immunoaffinity purified but was never seen when PAS was used for Ig purification. Control experiments exclude the binding of this protein non-specifically either to Sepharose or to Igs or to other CSF proteins. Analysis of purified Igs under non-reducing conditions leads to some reduction in staining pattern indicating that a portion of the protein may be disulfide linked to itself or to other CSF proteins. Immunoblot analysis of CSF Igs separated on 2 DE gels is consistent with a portion of the total CSF Ig protein existing as "free" heavy (H)-chains. PAS requires dimeric Fc fragment of Ig for binding; the differences in 2-DE gels of PAS and immunoaffinity purified Igs may be due to interaction of the 74,000-80,000 protein with "free" H-chain, which nevertheless, still leaves this complex available for binding by anti-H chain antisera. It has been previously suggested that the cytotoxicity of "free" H-chains is abrogated in the absence of the complementary L-chains by H-chain binding proteins; the protein reported here has features similar to these proteins reported previously and may be involved in some way in regulating Ig production in the MS central nervous system. PMID- 3099177 TI - Interaction of bovine erythrocyte N-glycolylneuraminic acid-containing gangliosides and glycoproteins with a human Hanganutziu-Deicher serum. AB - A human Hanganutziu-Deicher (H-D) serum reacted with N-glycolylneuraminic acid (NeuGc)-containing gangliosides and glycoproteins isolated from bovine erythrocyte membranes. Three populations of H-D antibodies were identified in the human H-D serum. One population very likely recognized the NeuGc-Gal sequence; a second population appears to recognize additional sugars in the oligosaccharide sequence, e.g. NeuGc-Gal-GlcNAc; while a third population may also recognize polypeptide determinants in addition to the NeuGc-Gal-GlcNAc sequence. The H-D serum distinguished two high mol. wt glycoproteins (HMGP I and II) present in crude extracts of bovine erythrocyte membranes. These glycoproteins were separated by repetitive fractionation on Sephacryl S-1000 in the presence of urea and their composition determined. PMID- 3099178 TI - A pre-translational defect in a case of human mu heavy chain disease. AB - A patient (BW) was studied with Mu heavy chain disease (mu HCD) in whom a leukemic B-cell clone secreted a shortened monoclonal mu chain without associated light chain. The cells did, however, produce a normal-sized kappa light chain that was detected as urinary Bence-Jones protein. The cytoplasmic and secreted monomeric mu chain had an approximate mol. wt of 58,000. Radiochemical sequence analysis of the biosynthetically labelled mu chain revealed a protein that lacked the entire variable region. The sequence initiated at amino acid position 5 within the first constant region domain (CH1) of C mu. The primary in vitro translation product, the cytoplasmic and secreted proteins were all similarly truncated, thereby excluding extensive postsynthetic degradation. The mu RNA, that directed the synthesis of the truncated mu protein, was about 350 bp smaller than the normal mu RNA. Furthermore, by primer extension analysis it was possible to localize this deletion in the mu RNA to a region 5' of CH1. Thus, a defect at the level of Ig gene structure/assembly that deletes coding information or results in aberrant RNA processing must be responsible for the truncated mu HCD protein BW. PMID- 3099179 TI - Correlation of the character of intramolecular melting with digestibility by pepsin in precipitating and non-precipitating pig anti-Dnp antibodies. AB - Precipitating and non-precipitating pig anti-2,4-dinitrophenyl group (Dnp) antibodies were investigated by differential adiabatic scanning microcalorimetry in the pH range 3.7-4.5. The partial heat capacity functions obtained revealed a notable difference between the two antibody types when the analysis was done at pH 4.5 or 4.0. The transition observed at temps around 50 degrees C in a non precipitating antibody was absent in a precipitating antibody. Under analogous conditions, pH 4.5, the precipitating antibody was fully resistant to pepsin, while the non-precipitating antibody yielded appropriate F(ab')2 and pFc'fragments. At pH 3.7 no substantial difference in the partial heat capacity function could be observed between the two antibody types. Below pH 4.0 the precipitating antibody became susceptible to peptic cleavage and yielded fragments of the same general character as the non-precipitating antibody. This finding lends support to the view that the structural block in immunoglobulin G that melts first, i.e. at temps near 50 degrees C, is the CH2 domain or a part of it. PMID- 3099180 TI - Serologic variations in kappa light chains of various Mus species correlate with differences in gene structure. AB - Kappa light chains were investigated in sera of several groups of wild derived mouse strains by radioimmunological analysis using xenogeneic anti-mouse kappa light chain antibodies. Although the majority of strains tested expressed serologically indistinguishable kappa chains, several significant exceptions were observed. Anti-kappa chain reactivity was not detectable in normal sera of Mus caroli and Mus cervicolor species using specific antiserum. These strains express a variant of the kappa light chain. Some serologic variation was also observed in kappa chains from members of the subgenus Nannomys. Southern blot analyses using C kappa and J kappa probes indicated different patterns of hybridization in strains that were serologically distinguishable. Mus caroli and Mus cervicolor DNAs digested with the enzymes EcoRI or BamHI show variation from BALB/c and most other mouse strains tested in the size of the hybridizing fragments. This correlation between serologic and blotting analyses is no longer found in SJL and SPE strains, which show variation in BamHI cleavage but not at the serological level. The majority of laboratory and wild derived mice analyzed have the same pattern of hybridization. Taken together our results may also have implications for the phylogenetic classification of wild type mouse strains. PMID- 3099181 TI - Monoclonal IgM/A hybrid antibodies: artifacts due to anti-idiotype (T15) antibodies in commercial anti-alpha sera. AB - A mouse hybridoma antibody, with specificity for Trichinella spiralis, was found to react against both anti-mu and anti-alpha sera obtained from two to three commercial sources. It also had a unique electrophoretic mobility, bound to staphylococcal protein A, and was comprised of a single type of heavy chain (mu like) and light chain (kappa). However, Northern blot analysis of RNA extracted from the corresponding hybridoma cells revealed only mu but no alpha message. Subsequent studies on the protein, as well as on a similar "hybrid" antibody previously described, using antisera raised to the antibody but which had been absorbed against normal mu and alpha determinants, suggested an idiotype common to both antibodies: this was intuitively guessed, and later confirmed, to be the phosphorylcholine-specific T15 idiotype. It was further shown that anti-T15 antibodies prevailed in the commercial anti-alpha sera and these (rather than alpha-chain specific antibodies) were responsible for the cross-reactivities of the sera with the hybrid antibodies. PMID- 3099182 TI - Serotoninergic structures and onset of the circadian corticosterone rhythm. PMID- 3099183 TI - Gonadotropins and gonadal function in transsexualism and hypospadias. PMID- 3099184 TI - [Characteristics of expression of the tetracycline resistance gene from the plasmid pBR322 in Bacillus subtilis cells]. AB - The expression of Tc resistance gene derived from plasmid pBR322 has been studied in Bacillus subtilis cells where this alien gene is not usually expressed. Fragments of Bacillus subtilis chromosome were inserted into the Tc resistance gene promoter region of the hybrid plasmid pGG20 and the expression of this gene was registered. Plasmid pGG20 confers a constitutive mode of Tc resistance in Escherichia coli cells. In contrast, the inducibility of Tc resistance gene expression in Bacillus subtilis cells has been reported. Optimal concentration for the highest inducibility of Tc resistance by the antibiotic has been determined. PMID- 3099185 TI - Aflatoxin B1 activation to a plasmid mutagen by a chemical model of cytochrome P 450. AB - Aflatoxin B1 (AFB1) was oxidised by a chemical model of cytochrome P-450 and the products obtained analysed by reversed-phase hplc. The oxidation system employs a water-insoluble iron(III)porphyrin catalyst (tetraphenylporphinatoiron(III) chloride; FeTPPCl) and an oxygen donor, iodosylbenzene (PhIO). The two AFB1 products obtained from this reaction were derived by initial oxidation across the 8-9 double bond of AFB1 and subsequent breakdown of AFB1-8,9-epoxide, the compound postulated to be the ultimate carcinogenic and mutagenic derivative of AFB1. Oxidation of AFB1 by the porphyrin-catalysed system in the presence of calf thymus DNA, resulted in the formation of AFB1-DNA adducts identical to those formed in vivo and in vitro after liver mono-oxygenase activation. The chemical model system was therefore used on a microscale to react AFB1 with plasmid pHR1800, a plasmid containing the genes for beta-lactamase (amp-r) and galactokinase (galK). AFB1-modified plasmid DNA was then transformed into E. coli AB1886 (uvrA-) and the effects of the AFB1-DNA adducts on plasmid survival and the ability of pHR1800-transformed bacteria to metabolise galactose, were then studied. The results showed an AFB1 dose-dependent decrease in plasmid survival and increase in the mutation frequency of the galK gene only when the complete oxidation system was used to generate the reactive AFB1 metabolite. PMID- 3099186 TI - Uncoupling of the induction of mutations and sister-chromatid exchanges by the replication of 5-bromouracil-substituted DNA. AB - The REP mutagenesis protocol, which involves the replication of 5-bromouracil (BrUra)-substituted DNA in the presence of deoxyribonucleoside triphosphate (dNTP) pool imbalance, has been shown to induce both mutations and sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells. However, when a Syrian hamster melanoma-derived cell line, called 2E, which was selected for its ability to replace all of the thymine residues in DNA with BrUra, was subjected to the REP mutagenesis protocol, the correlation between the induction of mutations and SCEs was no longer observed. The 2E cells were found to be much more sensitive to the induction of mutations by REP mutagenesis than were the CHO cells. This increased sensitivity to REP mutagenesis was found to correlate with increased perturbations of the dNTP pools that have been shown to be involved in the mutagenic mechanism of this protocol. In contrast, when the induction of SCEs by the REP protocol was measured, it was found that although a baseline level of SCEs was detected in 2E cells, no significant induction of SCEs due to dNTP pool perturbation was observed. It was shown that high levels of SCEs were readily induced in 2E cells by other agents, e.g. mitomycin C. A model, which discusses the fate of mismatched bases thought to be generated by the REP mutagenesis protocol as the determining factor for the induction of mutations of SCEs, is proposed to explain the uncoupling of mutagenesis and SCE induction in 2E cells. PMID- 3099187 TI - Sister-chromatid exchanges induced by mitomycin C after exposure of human lymphocytes in G0 to a low dose of X-radiation. AB - Human peripheral blood lymphocytes from 20 donors were exposed in G0 to mitomycin C with and without prior acute irradiation with 0.01 Gy of 250 kVp X-rays. No evidence was found for the radiation having an hormetic effect on the level of sister-chromatid exchanges induced by mitomycin C. PMID- 3099188 TI - Positive correlation between the occurrence of chromosome breakage and the induction of point mutations associated with male recombination 31.1 MRF system of hybrid dysgenesis in Drosophila melanogaster. AB - One of the weak singed (snw) mutations, induced by the 31.1 MRF in the X chromosome of a laboratory strain, is highly unstable, often changing to either a strong expression (snst) or reverting to wild type (sn+). The present study shows that the X-chromosome carrying the (snw) mutation and the X-chromosome carrying one of the snst alleles derived from the snw mutation generate different frequencies of deletions associated with the w locus. Moreover, they produce different frequencies of mutations associated with the w locus in males after the reintroduction of the 31.1 MRF second chromosome. The occurrence of the deletions and the induction of the mutations are positively correlated and increase when flies are raised at a higher temperature. These data indicate that the induction of the w mutations follows the generation of chromosome breaks in the w locus. The break-points of the recovered deletions occurred in specific sites in the 3C subdivision. Furthermore both snw and snst X-chromosomes induce different frequencies of non-disjunction in females depending on the culture temperature and the genetic background. The present data also show that the 23.5 MRF second chromosome which exhibits specific differences in its activities from the 31.1 MRF is unable to induce w mutations. This fact supports our previous indications that the 31.1 MRF and the 23.5 MRF are not identical. PMID- 3099189 TI - Effects of H-2 complex and non-H-2 background on urethane-induced chromosomal aberrations in mice. AB - The incidence of in vivo urethane-induced chromosomal aberrations was examined in H-2 congenic strains of mice with B10 and A backgrounds. Chromosome analysis of bone-marrow cells could divide 7 lines of A.H-2 congenic strains into 2 groups: one with a higher frequency of chromosomal aberrations such as in A/Wy (haplotype H-2a), A/J (H-2a), A.AL (H-2al) and A.TL (H-2tl), and the other consisting of A.TH (H-2t2), A.CA (H-2f), A.BY (H-2b) and A.SW (H-2s). The same tendency was also observed in the spleen cells. Among B10.H-2 congenic mice, B10.A (H-2a), B10.BR (H-2k), B10.A(3R) (H-2i3), B10.A(5R) (H-2i5) and B10.S(9R) (H-2t4) exhibited significantly higher rates of induced chromosomal aberrations than those in B10 (H-2b), B10.S (H-2s), B10.A(2R) (H-2h2), B10.A(4R) (H-2h4) and B10.S(7R) (H-2t2). To determine the effect on non-H-2 genetic backgrounds on urethane-induced chromosomal aberrations, 4 pairs of strains which have the same H-2 haplotypes, such as in B10 vs. A.BY (H-2b), B10.A vs. A/Wy (H-2a), B10.S vs. A.SW (H-2s), and B10.S(7R) vs. A.TH (H-2t2), were compared. The strains with a B10 background exhibited significantly higher frequencies of deletions and lower frequencies of exchanges than the strains with an A background. These data suggested that at least two genes are involved in the regulation of urethane induced chromosomal aberrations in mice, one of which is mapped between the S and D regions in the H-2 complex, and another not belonging to H-2. PMID- 3099190 TI - Induction of SOS and adaptive responses by alkylating agents in Escherichia coli mutants deficient in 3-methyladenine-DNA glycosylase activities. AB - The induction of SOS and adaptive responses by alkylating agents was studied in Escherichia coli mutants tagA and alkA deficient in 3-methyladenine-DNA glycosylase activities. The SOS response was measured using an sfiA::lacZ operon fusion. The sfiA operon, in the double mutant tagA alkA, is induced at 5-50-fold lower concentrations of all tested methylating and ethylating compounds, as compared to the wild-type strain. In all cases, the tagA mutation, which inactivates the constitutive and specific 3-alkyladenine-DNA glycosylase I (TagI), sensitizes the strain to the SOS response. The sensitization effect of alkA mutation, which inactivates the inducible 3-alkyladenine-DNA glycosylase II (TagII), is observed under conditions which allow the induction of the adaptive response. We conclude that the persistence of 3-methyladenine and 3-ethyladenine residues in DNA most likely leads to the induction of the SOS functions. In contrast, the adaptive response, evaluated by O6-methylguanine-DNA methyltransferase activity in cell extracts, was not affected by either tagA or alkA mutations. The results suggest that the SOS and adaptive responses use different alkylation products as an inducing "signal". However, adaptation protein TagII inhibits the induction of the SOS response to some extent, due to its action at the level of signal production. Finally, we provide conditions to improve short-term bacterial tests for the detection of genotoxic alkylating agents. PMID- 3099191 TI - Mutations at the mei-41, mus(1)101, mus(1)103, mus(2)205 and mus(3)310 loci of Drosophila exhibit differential UDS responses with different DNA-damaging agents. AB - 5 mutagen-sensitive mutants of Drosophila melanogaster, reported to perform normal or only slightly reduced excision repair of UV damage, were examined by an unscheduled DNA synthesis (UDS) assay. This assay measures the ability of cultured primary cells, derived from each mutant, to perform the resynthesis step in the excision repair pathway, following damage to cellular DNA by direct-acting alkylating agents, UV or X-irradiation. 2 mutants, classified as completely or partially proficient for both excision and postreplication repair of UV damage, mus(1)103 and mus(2)205, were found to give positive UDS responses only for UV damage. These mutants exhibit no measurable UDS activity following DNA damage by several different alkylating agents and X-rays. 3 mutants, classified as having no defect in excision repair, but measurable defects in postreplication repair of UV damage, mei-41, mus(1)101, and mus(3)310 exhibit 3 different response patterns when tested with the battery of agents in the UDS assay. The mutant mei-41 exhibits a highly positive UDS response following damage by all agents, consistent with its prior classification as excision-repair-proficient, but postreplication-repair-deficient for UV damage. The mutant mus(1)101, however, exhibits a strong positive UDS response following only UV damage and appears to be blocked in the excision repair of damage produced by both alkylating agents and X-irradiation. Finally, mus(3)310 exhibits no UDS response to alkylation, X ray or UV damage. This is not consistent with its previous classification. Results obtained with the quantitative in vitro UDS assay are entirely consistent with the results from two separate in vivo measures of excision repair deficiency following DNA damage, larval hypersensitivity to killing and hypermutability in the sex-linked recessive lethal test. PMID- 3099192 TI - Synaptonemal complex damage as a measure of chemical mutagen effects on mammalian germ cells. AB - As heritable chromosome anomalies are implicated in a variety of human disabilities, their induction in germ cells by environmental chemicals is viewed as a threat to health (National Research Council, 1982; Hook, 1983). Synaptonemal complex (SC) analysis is a novel approach for the detection of germ-line chromosomal damage. This sensitive cytological procedure reveals induced structural damage and pairing abnormalities in SCs of meiotic prophase chromosomes, together with other germ-line toxic effects, in the testes of rodents treated with mitomycin C and cyclophosphamide. Our results demonstrate the effectiveness of SC analysis as a rapid and practical in vivo germ-line mutagen assay that lacks many of the short-comings of existing tests. PMID- 3099193 TI - A benzo[a]pyrene metabolite-DNA adduct occurring in the activating cell but not in exogenous DNA. AB - [3H]Benzo[a]pyrene (BP) and salmon sperm DNA were incubated with hepatocytes from 5,6-benzo-flavone-treated rats. The cellular DNA and the exogenously added DNA were separately isolated, hydrolyzed and chromatographed on a Sephadex LH-20 column. The extracellular DNA yielded 3 peaks of radioactivity in the chromatographic eluate. The cellular DNA contained an additional peak suggesting the formation of a DNA adduct from a metabolite that does not leave the cell. PMID- 3099194 TI - Measurement of micronuclei by cytokinesis-block method in cultured Chinese hamster cells: comparison with types and rates of chromosome aberrations. AB - The cytokinesis-block method of Fenech and Morley (1985) has been tested for the enumeration and characterization of micronuclei in exponentially growing Chinese hamster cells in culture. The consistent dose-response relations were obtained in cultures treated with mitomycin C, caffeine and colcemid. Comparison with the chromosome aberration frequencies indicated that approximately 30% of the acentric chromosomes are expressed as micronuclei in the mitomycin C and caffeine treated cells. The size distribution of the micronuclei suggested that the base line frequency of micronuclei is mainly a reflection of mitotic dysfunctions rather than chromosome structural aberrations. PMID- 3099195 TI - Menopause clinic offers counsel and care. PMID- 3099196 TI - National Awareness Week targets child passenger safety. PMID- 3099197 TI - Management of isoimmunized pregnancy. PMID- 3099198 TI - Long-term effect of a first pregnancy on the secretion of prolactin. AB - An early first pregnancy is known to protect against subsequent breast cancer. We speculated that this effect may be mediated by a long-term depression of prolactin secretion after pregnancy. We therefore measured basal and post stimulation serum levels of prolactin, luteinizing hormone (LH), and follicle stimulating hormone (FSH) in two groups--15 women 18 to 23 years of age and 9 women 29 to 40--before and after a first full-term pregnancy, and in 40 appropriate nulliparous controls. We observed no significant change in basal levels of serum LH or FSH or in the levels stimulated by gonadotropin-releasing hormone in any group. A significant decrease was seen, however, in basal and perphenazine-stimulated levels of prolactin after pregnancy in both the younger and older first-pregnancy groups but not in the controls. In a separate cross sectional study, we compared basal serum prolactin levels in 29 parous and 19 nulliparous women of similar age. The serum prolactin levels were significantly lower in the parous group but were not related to the number of pregnancies (one to three) or the time elapsed (12 to 150 months) since the last delivery. We conclude that a first pregnancy leads to a long-term decrease in serum prolactin secretion, lasting at least 12 to 13 years. PMID- 3099200 TI - Parenteral and enteral nutrition: update. PMID- 3099199 TI - Effect of cyclopiazonic acid on delayed hypersensitivity to Mycobacterium tuberculosis, complement activity, serum enzymes, and bilirubin in guinea pigs. AB - Cyclopiazonic acid (CPA) was given daily to groups of guinea pigs at doses of 0.00625, 0.0125, 0.025, 0.05, 0.1, 0.2, 0.4, 0.8, 1.6, and 1.95 mg/day for 30 days. All guinea pigs were sensitized and survivors were skin tested twenty-five days later with Mycobacterium tuberculosis. Mortalities occurred only in the two greatest dose groups. Signs of disease included anorexia, roughened hair coat, diarrhea and incoordination. The major histopathologic changes occurring in these two groups included hepatocellular vacuolar degeneration and necrosis of the gastric mucosa with infiltration of neutrophils in the deep gastric mucosa. CPA did not affect cutaneous hypersensitivity to M. tuberculosis, complement activity, serum glycocholic acid concentrations or weight gains. There were increases in aspartate aminotransferase, alanine aminotransferase, and sorbitol dehydrogenase concentrations in the serum of guinea pigs in the two greater dose groups, but no changes were found in serum concentrations of SAP. There was a slight increase in the serum bilirubin concentrations in the greater dose groups. PMID- 3099201 TI - The process of smoking relapse. PMID- 3099202 TI - Commitment to abstinence and relapse to tobacco, alcohol, and opiates. PMID- 3099204 TI - Relapse to use of heroin, cocaine, and other drugs in the first year after treatment. PMID- 3099203 TI - Explaining relapse to opiate addiction following successful completion of treatment. PMID- 3099206 TI - Clinical implications of relapse research. PMID- 3099205 TI - Smoking cessation and relapse among cardiac patients. PMID- 3099207 TI - Relapse and recovery: some directions for research and practice. PMID- 3099208 TI - The drug dependence syndrome concept as an organizing principle in the explanation and prediction of relapse. PMID- 3099209 TI - Acquisition, maintenance, cessation, and reacquisition: an overview and behavioral perspective of relapse to tobacco use. PMID- 3099210 TI - Relapse and recovery in substance abuse careers. PMID- 3099211 TI - Theories of relapse and recovery and their implications for drug abuse treatment. PMID- 3099212 TI - Multivariate description of alcoholism careers: a 10-year followup. PMID- 3099213 TI - Relapse and recovery among opioid addicts 12 years after treatment. PMID- 3099214 TI - Polymorphism of human Ia antigens generated by reciprocal intergenic exchange between two DR beta loci. AB - Class II molecules encoded by the human major histocompatibility complex (MHC) are involved in regulating T-cell response to antigens. The mechanisms for generating polymorphism in products of the MHC have been studied extensively for both the murine H-2 and the human HLA complex. Such studies indicate that point mutations plus selection have a major role in the generation of polymorphisms of class I and class II MHC genes. However, a non-reciprocal gene conversion mechanism has been proposed to explain several examples of clustered sequence variation in MHC genes. In all these examples, the proposed gene conversion event is unidirectional; that is, one of the two interacting genes acts as sequence donor and the other as sequence recipient. No examples of potential reciprocal genetic exchange (as occurs in the fungal system), in which the two interacting genes act as both donor and recipient of gene fragments, have been found in the MHC system or in other multigene families of higher organisms. We sequenced two different HLA-DR beta complementary DNAs from each of two different cells all expressing the same serologically defined determinant (DR2) but different T-cell recognized (Dw) specificities (Dw12 and MN2). Sequence comparisons of these four cDNA clones (and two DR beta amino-acid sequences from the DR2-Dw2 subtype) suggest that new coding sequences for DR beta molecules in the DR2 haplotypes are potentially generated by reciprocal intergenic exchange. PMID- 3099215 TI - Prospects for 1987. United States. Health spending still increasing but space science stalled. PMID- 3099217 TI - [Is long-term institutionalization in a general psychiatric hospital always a mistake?]. PMID- 3099216 TI - Blebbing, free Ca2+ and mitochondrial membrane potential preceding cell death in hepatocytes. AB - Cell surface 'blebbing' is an early consequence of hypoxic and toxic injury to cells. A rise in cytosolic free Ca2+ has been suggested as the stimulus for bleb formation and the final common pathway to irreversible cell injury. Here, using digitized low-light video microscopy, we examine blebbing, cytosolic free Ca2+, mitochondrial membrane potential and loss of cell viability in individual cultured hepatocytes. Unexpectedly, we found that after 'chemical hypoxia' with cyanide and iodoacetate, cytosolic free Ca2+ does not change during bleb formation or before loss of cellular viability. Cell death was precipitated by a sudden breakdown of the plasma membrane permeability barrier, possibly caused by rupture of a cell surface bleb. PMID- 3099218 TI - Clinical use of lithium in manic-depressive illness. PMID- 3099219 TI - Combination of bacteriostatic and bactericidal antibiotics in the treatment of acute salpingitis. PMID- 3099220 TI - Fibular lengthening to correct a malunited ankle fracture. PMID- 3099221 TI - von Recklinghausen's neurofibromatosis and primary hyperparathyroidism: a case report and literature review. PMID- 3099222 TI - Effect of various hypothalamic deafferentations injuring different parts of the GnRH pathway on ovulation, GnRH content of the median eminence, and plasma LH and FSH levels. AB - Various supra- and retrochiasmatic cuts injuring different parts of the septo preoptico-infundibular GnRH pathway were made in adult female rats, and their effects on ovulation, median eminence (ME) GnRH content and on plasma LH and FSH levels were studied. Extended retrochiasmatic frontal cut just behind the optic chiasm, or a frontal cut in front of the suprachiasmatic nucleus presumably interrupting the whole GnRH pathway blocked ovulation, led to persistent estrus with polyfollicular ovaries, and reduced the ME GnRH content to 10 and 32%, respectively, expressed in percentage of unoperated control value. Severance of the GnRH pathway on one side or partial interruption of the pathway on the two sides in the retrochiasmatic area did not interfere with ovulation, and the ME GnRH content was 50% or more of the control value. Disconnection of the GnRH fibers coming from the septum resulted in a more than 30% decrease in the GnRH content of the ME, but did not block ovulation. Two separate symmetrical lateral cuts in the suprachiasmatic area leaving intact the presently known GnRH pathway reduced the ME GnRH content to 40% of the intact value, but did not interfere with ovulation. Plasma LH and FSH levels of the animals with different knife cuts were considerably dissociated and there were no apparent correlations between brain interventions and the concentrations of these two hormones in the blood. Our previous findings together with the present data suggest that: half of the GnRH pathway, medial or lateral bundles of the pathway on the two sides are sufficient for ovulation and cyclic gonadotrophic function; persistent estrus develops if the ME GnRH content is below 40% of the control value, and about 60% of the ME GnRH originates outside the preoptic, supra- and retrochiasmatic region. Half of this 60% may come from the septum and the vertical part of the diagonal band of Broca, the other half from the region in front of the preoptic area. The remaining 40% presumably arises from the preoptic (7-10%), supra- (15 20%) and retrochiasmatic region (8-10%). PMID- 3099223 TI - Effects of the benzodiazepine antagonists RO 15-1788, CGS-8216 and PK-11195 on amygdaloid kindled seizures and the anticonvulsant efficacy of diazepam. AB - The anticonvulsant effectiveness of the benzodiazepine antagonists RO 15-1788, CGS-8216 and PK-11195 were evaluated against threshold and suprathreshold (400 microA) stimulation in fully amygdaloid-kindled rats. Pretreatment with either RO 15-1788 (3, 10 and 30 mg/kg), CGS-8216 (3, 10 and 30 mg/kg) or PK-11195 (10 and 60 mg/kg) failed in this study to modify consistently either the afterdischarge thresholds or elicited suprathreshold seizures or duration of afterdischarge. Using a double injection paradigm, the effectiveness of these three benzodiazepine antagonists to reverse the anti-convulsant and behavioral effects of diazepam were studied. When diazepam (3 mg/kg) was injected 15 min before or after a second injection of the vehicle control DMSO (0.25 ml/kg), a significant reduction in the duration of afterdischarge and seizure rank, elicited by a suprathreshold stimulation in amygdaloid-kindled rats, occurred. When either CGS 8216 (10 mg/kg) or RO 15-1788 (10 mg/kg) were given 15 min before diazepam (3 mg/kg) prior to stimulation, the anticonvulsant properties of diazepam were blocked. When RO 15-1788 (10 mg/kg) was given 15 min after diazepam, antagonism of the anticonvulsant effects on diazepam was shown. However, when either CGS 8216 (10 mg/kg) or PK-11195 (10 and 60 mg/kg) were given 15 min after diazepam (3 mg/kg), the anticonvulsant properties of diazepam were not blocked. The anticonvulsant effects of diazepam were reversed when CGS-8216 (10 mg/kg) was given 5 min after diazepam (3 mg/kg) or when a larger dose (30 mg/kg) was given at the same 15 min interval.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099224 TI - 5-Hydroxytryptamine M-receptor antagonism in the hypothalamus facilitates gastric emptying in the guinea-pig. AB - The injection of 5-hydroxytryptamine (5-HT) and 2-methyl-5-HT into the perifornical area of the hypothalamus of the guinea-pig reduced the emptying of barium sulphate spheroids from the stomach. In contrast, the injection of the 5 HT M-receptor antagonist ICS 205-930 into the same area of the hypothalamus enhanced gastric emptying and attenuated the inhibitory effect of 5-HT. Similar injections of methysergide and ritanserin were without effect. It is concluded that an endogenous hypothalamic 5-HT system may inhibit gastric emptying through a 5-HT M-receptor mechanism which may afford a site of action for 5-HT agonist and antagonist drugs to modify gastric emptying. PMID- 3099226 TI - Hospital stays by diagnosis related group for neurologic patients treated medically. AB - We analyzed differences in hospital stays by diagnosis related group for neurologic patients treated medically in Sacramento, CA, and Syracuse, NY, between 1981 and 1984. Differences between stays were highest for DRGs with large proportions of elderly discharges, especially those with cerebrovascular disorders. Length of stay variability was also higher for DRGs with large proportions of elderly. These results suggest that extended hospital stays for neurology patients result from approaches to patient management, rather than demographic patterns, availability of hospital or long-term care beds, or the extent of health maintenance organization activity. PMID- 3099227 TI - Antineural antibodies in the serum of patients with amyotrophic lateral sclerosis. AB - Sera from 12 patients with amyotrophic lateral sclerosis (ALS) and 18 controls were screened for antineural antibodies using immunoblotting. No consistent differences were detected between ALS patients and controls, although antibodies to 52,000- and 70,000-dalton proteins in mouse spinal cord were somewhat more common in ALS sera. Antibodies to a protein of approximately 150,000 to 200,000 daltons were also evident. The 70,000- and 52,000-dalton proteins were detected in brain, cerebellum, and liver as well as spinal cord. Immunohistochemistry suggested antibody activity was directed at least in part to neurofilaments. While the antibodies to the 52,000- and 70,000-dalton proteins were more common in ALS than control sera (p less than 0.02 and less than 0.05, respectively), it is not clear from this initial study that this difference is of clinical or etiologic significance. PMID- 3099225 TI - The systemic approach to the stability and plasticity of neurophysiological processes during adaptive brain activity. AB - The problem of the stability and adaptability of regulatory processes is considered, taking as a point of departure N. P. Bekhtereva's theory regarding stable pathological states, and inflexible and adaptable links in control systems. The need to introduce a probabilistic approach is emphasized. Generalizations are made on materials relating to the connectability of the separate components of the biorhythms of functional systems, and to the stability of their amplitude-frequency characteristics. The corpus of facts permitted the successful development in clinical practice of functional biocontrol and feedback. PMID- 3099228 TI - TRH and amyotrophic lateral sclerosis. PMID- 3099230 TI - [Total enteral nutrition in the critical patient requiring surgery]. PMID- 3099229 TI - [PaCO2 during mechanical ventilation with Bain circuit]. PMID- 3099231 TI - Taking the confusion out of multiple infusion: i.v. medications and TPN. PMID- 3099232 TI - Solitary diverticulum of the cecum. PMID- 3099234 TI - Skill month: an on-the-job project. PMID- 3099233 TI - Prospective payment begins for Medicare SNF care. PMID- 3099235 TI - Prognostic factors: cisplatin regimens for patients with ovarian cancer after failure of chemotherapy. AB - For 129 ovarian cancer patients failing prior chemotherapy, overall clinical response rates were: 21% with cisplatin, 36% with cisplatin plus doxorubicin, 52% with cyclophosphamide added to the two drugs, and 44% with hexamethylmelamine added to the three drugs. Median survival was six or seven months in each trial. Twenty-five percent of the patients survived nine months with cisplatin and 14 to 16 months with each of the three combinations. Characteristics associated with best rate of response included: performance status 1 (completely ambulatory), age greater than or equal to 50, residual tumor less than or equal to 5 cm, and two or less prior cytotoxic drugs. In multivariate analyses, performance status dominated, although age and possibly treatment (cisplatin versus others) were significant. With performance status removed from the model, all of the remaining factors became significant. Factors associated with best survival included: performance status 1, tumor size less than or equal to 5 cm, and complete or partial response. In a multivariate analysis for survival, performance status entered the model. In a series of analyses with performance status removed, tumor size or response entered the model. These findings provide reasons to study both treatment with cisplatin before disease progression reduces the number of favorable characteristics and systematic second attempts at debulking surgery. PMID- 3099236 TI - Prolactin secretion after surgery or bromocriptine treatment of prolactinoma. AB - In prolactinoma patients, the unresponsiveness of prolactin (PRL) to dynamic tests with thyrotropin-releasing hormone (TRH) or dopamine agonist or antagonist drugs suggests that the disease is caused by the failure of central dopaminergic inhibition. The absence of PRL secretory response to dopamine or TRH in prolactinoma patients also may be an effect of the disease. Twenty-six women diagnosed by dynamic tests and radiologic examination as having PRL-secreting adenoma were treated surgically (15) or with bromocriptine (11) and their condition was evaluated one to three years later by TRH, nomifensine, and domperidone tests. Basal PRL levels decreased after surgery and bromocriptine treatment. At the time of the follow-up study, PRL levels were elevated in six of the 15 surgically treated patients and in six of the 11 treated with bromocriptine. Thyrotropin-releasing hormone, nomifensine, and domperidone produced standard PRL responses in normoprolactinemic patients but not in hyperprolactinemic patients. These results indicate that the alteration of TRH or dopaminergic receptors in the regulation of PRL secretion in prolactinoma is related to the disease and disappears when the tumor is removed or treated successfully with bromocriptine. PMID- 3099237 TI - [Drug-resistant plasmids in clinically isolated Streptococcus faecalis]. PMID- 3099238 TI - Eagle's syndrome: a comparison of intraoral versus extraoral surgical approaches. AB - Eagle first described vague orofacial pain associated with styloid elongation in 1937. Since that time, many authors have described the various clinical symptoms, radiographic features, and treatment regiments seen with Eagle's syndrome. Two cases of Eagle's syndrome treated surgically are presented in this article. Both extraoral and intraoral approaches were separately used. These two surgical approaches are critically discussed in depth. The extraoral approach is advocated. In addition, diagnostic procedures and nonsurgical treatment alternatives are discussed. PMID- 3099239 TI - Histopathologic study of bone invasion by DMBA-induced carcinoma of the mouth in the hamster. AB - Carcinoma was induced in the floor of the mouth in the hamster, and the mechanism of bone invasion was studied microscopically. Conclusions are as follows: The periosteum is destroyed and, in general, the external surface of the cortical bone is resorbed through osteoclastic action. However, the periosteum at times resists the invasion of tumors. As the cortical bone is resorbed to some extent and tumor replaces the resorbed area, Volkmann and haversian canals begin to enlarge. Following enlargement of the canals, tumor invasion results in enlargement of the canals of the cortical bone far from the invaded area. In addition, tumors invade the periodontal space and resorb the inner surface of the alveolar bone. Tumors invade the bone marrow through the enlarged haversian canals or the periodontal space or by direct resorption of cortical bone, thus replacing the marrow spaces. PMID- 3099240 TI - Ethical issues in the care of patients with AIDS. PMID- 3099241 TI - Ethical issues in AIDS research. PMID- 3099243 TI - Training volunteers in home care for patients with AIDS. PMID- 3099242 TI - Ensuring quality hospice care for the person with AIDS. PMID- 3099244 TI - [Management of true precocious puberty with a delayed-action Gn-RH analog]. PMID- 3099245 TI - [Effect of antioxidants of the gutimine group on the course and outcome of the post-resuscitation process]. PMID- 3099246 TI - [Mechanism of the toxic effect of carbogen on the brain]. PMID- 3099247 TI - [Effect of cobalt on blood gas composition, 2,3-diphosphoglycerate level in the erythrocytes and the erythropoietin level in the blood serum]. PMID- 3099248 TI - Antibody to multiple mucoid strains of Pseudomonas aeruginosa in patients with cystic fibrosis, measured by an enzyme-linked immunosorbent assay. AB - The sera from 32 patients with cystic fibrosis who were chronically colonized with mucoid strains of Pseudomonas aeruginosa (MPA) were tested for anti-MPA antibodies. Using an enzyme-linked immunosorbent assay we measured IgA, IgG, and IgM antibody titers to three MPA strains, extracts of those strains, and seaweed derived sodium alginate, which is similar chemically to the exopolysaccharide of MPA. These titers were compared with identical tests performed on the sera of eight cystic fibrosis patients who never were colonized with MPA and 10 normal adults. The IgG titers were significantly higher in tests of sera from the colonized patients compared with the other two groups but the IgA and IgM titers were not significantly higher. In colonized patients antibody titers to the different antigens correlated with each other suggesting that the major antibody response was to common antigenic determinants. Using these titers as a data base, eight patients whose clinical status was unknown to the testers, had IgG-enzyme linked immunosorbent assay tests of their sera and the four colonized patients with cystic fibrosis were correctly identified. Three of them had substantial titers of antibody in the bronchoalveolar lavage fluid. PMID- 3099249 TI - Waste nitrogen excretion via amino acid acylation: benzoate and phenylacetate in lysinuric protein intolerance. AB - Benzoate and phenylacetate improve prognosis in inherited urea cycle enzyme deficiencies by increasing waste nitrogen excretion as amino acid acylation products. We studied metabolic changes caused by these substances and their pharmacokinetics in a biochemically different urea cycle disorder, lysinuric protein intolerance (LPI), under strictly standardized induction of hyperammonemia. Five patients with LPI received an intravenous infusion of 6.6 mmol/kg L-alanine alone and separately with 2.0 mmol/kg of benzoate or phenylacetate in 90 min. Blood for ammonia, serum urea and creatinine, plasma benzoate, hippurate, phenylacetate, phenylacetylglutamine, and amino acids was obtained at 0, 120, 180, and 270 min. Urine was collected in four consecutive 6-h periods. Alanine caused hyperammonemia: maximum increase 107, 28-411 microM (geometric mean, 95% confidence interval); ammonia increments were nearly identical after alanine + benzoate (60, 17-213 microM) and alanine + phenylacetate (79, 13-467 microM) (NS). Mean plasma benzoate was 6.0 mM when extrapolated to the end of alanine + benzoate infusions; phenylacetate was 4.9 mM at the end of alanine + phenylacetate. Transient toxicity (dizziness, nausea, vomiting) occurred in four patients at the end of combined infusions, and we suggest upper therapeutic plasma concentrations of 4.5 mM for benzoate and 3.5 mM for phenylacetate. Benzoate and phenylacetate then decreased following first order kinetics with t1/2S of 273 and 254 min, respectively. Maximal plasma hippurate (0.24, 0.14-0.40 mM) was lower than maximal phenylacetylglutamine (0.48, 0.22-1.06 mM, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099251 TI - The microvascular response of the neonatal mesentery to hypertonic feedings. AB - Using intravital microscopy we studied the responses of the jejunal and ileal mesenteric microcirculation to hypertonic meals in neonatal piglets. Test meals were infused through a cannulated segment of proximal jejunum. The intestinal segments were observed under conditions of controlled temperature and humidity, and the velocity of red blood cells through mesenteric arterioles was measured and blood flow calculated. Jejunal flow was not altered from baseline by saline or hypertonic mannitol infusion, while significant increases in flow were observed during hypertonic glucose infusion (3.8 X 10(-6) versus 10.7 X 10(-6) ml/s, p less than 0.01). Jejunal glucose infusion did not cause shunting from the ileal microcirculatory bed. We conclude that the infusion of hypertonic glucose causes an increase in jejunal blood flow, but does not result in a change in ileal flow. The increase in flow is a local phenomenon related to glucose absorption in neonatal piglets. PMID- 3099250 TI - Serum insulin-like growth factors I and II concentrations and growth hormone and insulin responses to arginine infusion in children with protein-energy malnutrition before and after nutritional rehabilitation. AB - Serum insulin, growth hormone (GH), insulin-like growth factors (IGFs) I and II, cortisol, and albumin concentrations were measured in 15 children with kwashiorkor, 15 with marasmic-kwashiorkor, and 21 with marasmus, before and in the survivors, after nutritional rehabilitation, as well as in 10 underweight and eight normal Egyptian children. We also evaluated arginine-induced insulin and GH secretion. IGF-I concentrations were reduced in the three severely malnourished groups (0.07 +/- 0.03, 0.05 +/- 0.03, and 0.09 +/- 0.09 U/ml, respectively) but returned to normal after refeeding. IGF-II concentrations were low in the kwashiorkor (175 +/- 79 ng/ml), marasmic-kwashiorkor (111 +/- 57 ng/ml), and marasmic children (128 +/- 70.9 ng/ml) and returned to normal after nutritional rehabilitation. Basal GH levels were high in the three severely malnourished groups (21.9, 28.8, and 16.6 ng/ml, respectively) and returned to normal after refeeding (8.1, 6.5, and 6.0 ng/ml, respectively). GH responses to arginine were depressed in the three malnourished groups and improved significantly in marasmic kwashiorkor and marasmic children after nutritional rehabilitation. Insulin responses to arginine were impaired in kwashiorkor, and marasmic-kwashiorkor children and improved significantly after refeeding. IGF-I levels correlated significantly with percent of expected weight (r = 0.52, p less than 0.001), percent of expected height (r = 0.42, p less than 0.001), and weight/(height)2 index (r = 0.34, p less than 0.01). IGF-I levels correlated positively with insulin levels (r = 0.421, p less than 0.001) and negatively with cortisol concentrations (r = -0.400, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099252 TI - Effect of epidermal growth factor and artificial feeding in suckling rats. AB - To evaluate the effects of epidermal growth factor (EGF) in dietary milk, a new method of delivering an artificial (EGF-deficient) formula was developed using 42 rat pups, 1-14 days of age. In a second study the effect of EGF was evaluated in suckling rats from 3-11 days of age: group 1, mother-fed; group 2, mother-fed plus daily injections of EGF (0.1 micrograms/g body weight); group 3, artificial milk fed with added EGF (62 ng/ml); and group 4, artificial milk fed without EGF. Each group consists of nine rats. In group 2 there was premature eye opening and tooth eruption and a significant reduction in body weight and weight of liver, kidney, thyroid, and thymus but an increase in length of the intestine and weights of stomach, pancreas, lung, and adrenal (p less than 0.04), when compared to group 1. Both groups 3 and 4 showed premature tooth eruption and eye opening, and their body weights and most organ weights were similar to group 2; exceptions were a smaller stomach, thyroid, thymus, lung, and adrenal, which were similar to those in group 1. In addition, intestinal length in groups 3 and 4 were similar to the mother-fed EGF-treated pups (group 2). There was no difference in intestinal length between the artificially fed pups, whether or not they received oral EGF. These findings demonstrate a new and effective technique of artificial feeding and suggest that the increase in intestinal length caused by injections of EGF (0.1 micrograms/g body weight) can also be induced by feeding an artificial milk with or without physiologic levels of EGF. PMID- 3099253 TI - Different patterns of C3 and C4 activation in the varied types of juvenile arthritis. AB - Quantitative assays for C3 and C4 activation were carried out simultaneously on blood from children with varied types of juvenile arthritis. Factor VIII-related antigen was also measured as an indicator of vascular damage. In active systemic juvenile arthritis, the C4d/C4 ratio was frequently elevated and was usually associated with elevated C3d/C3 ratios and elevated concentrations of factor VIII related antigen. Children with chronic polyarticular arthritis, no matter which forms of onset they had had, also had increased levels of the C4d/C4 ratio, C3d/C3 ratio, and factor VIII-related antigen, but these were less consistent and were not associated with each other. In contrast, in pauciarticular arthritis there was a uniquely isolated increase in the C3d/C3 ratio. This work implies that there are different mechanisms responsible for complement activation in the different types and at different stages of juvenile arthritis. PMID- 3099254 TI - The effect of chemical sympathectomy on catecholamine release at birth. AB - The precise source of circulating catecholamine (CA) at birth and their role in circulatory adaptation is unclear. In order to determine the contribution of increased postganglionic sympathetic nerve activity to the CA surge at birth, we induced complete sympathectomy in near term fetal lambs prior to delivery by giving 6-hydroxydopamine. Chronically catheterized fetal sheep received either 6 hydroxydopamine (n = 5) or control infusion (n = 6). Chemical sympathectomy was verified by tyramine infusion. Lambs were delivered at 142 +/- 1 days of gestation and serial plasma CA, heart rate, blood pressure, cardiac output, blood gases, blood glucose, and free fatty acids, were measured before and for 4 h after delivery. Myocardial beta-adrenergic receptors and tissue CA concentration were determined following sacrifice. Baseline circulating norepinephrine (NE) values were lower in sympathectomized animals (183 +/- 45 versus 373 +/- 125 pg/ml, p less than 0.05) and epinephrine values were slightly higher (118 +/- 89 versus 48 +/- 1 pg/ml, NS). There was only a 2-fold increase in NE after cord cutting in sympathectomized animals while control animals had a 4-fold increase (peak NE values 354 +/- 121 versus 1305 +/- 363 pg/ml respectively, p less than 0.001). Epinephrine increased significantly in both groups and there were no significant differences between sympathectomized and control animals. Heart rate and blood pressure rose abruptly in both groups after cord cutting and there were no significant differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099255 TI - The accuracy and precision of an open-circuit system to measure oxygen consumption and carbon dioxide production in neonates. AB - We measured the oxygen consumption, carbon dioxide production, and respiratory quotient during the combustion of a known mass of anhydrous ethanol and methanol to assess the accuracy of an open-circuit flow-through system. Continuous measurements were made of the mass of alcohol burned, the velocity of gas flow through the apparatus, and simultaneous measurements of the fractional concentration of oxygen, carbon dioxide and nitrogen of the inlet and outlet gas using paramagnetic oxygen analyzer, infrared carbon dioxide meter, and mass spectrometer. Standard respiratory and stoichiometric equations were used to calculate the oxygen consumption, carbon dioxide production and RQ for the mass of absolute alcohol combustion per unit time. In a series of 12 consecutive laboratory experiments (on 7 days), the measured values of gas exchange (similar to the rate of respiratory gas exchange by an infant of 1-4 kg) were in agreement within 5% of the true values for ethanol and methanol combustion, confirming the validity of the open-circuit method. The paramagnetic oxygen analyzer and the mass spectrometer gave similar oxygen consumption results and differed very little when the rate of absolute alcohol combustion was used to quantify the accuracy of the complete measurement system. A positive measurement error was observed for the carbon dioxide production results from both the IR meter and mass spectrometer, with the result that the respiratory quotient measurements were 3.4-4.7% higher than the true value. The mass spectrometer gave more precise oxygen consumption results, whereas smaller variance of carbon dioxide production measurements was observed using the infrared CO2 meter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099256 TI - Day-to-day energy expenditure variability in low birth weight neonates. AB - We estimated the metabolic rate of 13 low birth weight infants over a 9-day period, using indirect calorimetry in conjunction with serial measurements of oxygen consumption, carbon dioxide production, and total urinary nitrogen excretion. The mean percent error for oxygen consumption and carbon dioxide production measurements (determined by alcohol combustion experiments) assignable to the open-circuit system was 0.4 and 3.8%, respectively. Error in the total urinary nitrogen excretion measurement was less than 1% by the Kjeldahl technique. In the clinical setting, however, the range of deviation of measured oxygen consumption, carbon dioxide production and total urinary nitrogen excretion was +/- 12, 12, and 15% of the mean value respectively for an individual patient under standardized controlled conditions. The variability of metabolic rate between infants may be as much as 76%. Factors that had a small effect on metabolic rate were difficult to detect because of the variability inherent in the short-term measurement of metabolic rate. It was virtually impossible to control the sources of variation in the resting metabolism of low birth weight neonates over extended experimental periods. Day-to-day variations in resting energy expenditure may explain, in part, the widely different growth rates of premature infants receiving similar caloric intakes. PMID- 3099257 TI - Questions about early enteral feeding study. PMID- 3099258 TI - [Amino acid content of the blood in premature newborn infants on various feeding methods]. PMID- 3099259 TI - [Digestion of milk proteins in premature infants in the 1st month of life]. PMID- 3099260 TI - [Comparative evaluation of various methods of feeding premature infants]. PMID- 3099261 TI - Monkey in the middle: pre-Darwinian evolutionary thought and artistic creation. PMID- 3099263 TI - [Studies on radiation therapy of carcinoma of the skin]. PMID- 3099262 TI - 36Cl fluxes in dispersed rat submandibular acini: effects of Ca2+ omission and of the ionophore A23187. AB - Transmembrane fluxes of 36Cl were investigated in dispersed acini of the rat submandibular gland in Ca2+-containing and Ca2+-free media and also in the presence of the divalent cation ionophore A23187. In Ca2+-replete medium, a time dependent uptake of tracer resulted in a steady state 36Cl content of 8.5 +/- 0.3 nmol/mg protein in 3-5 min. This uptake was reduced 32% by 1 mM furosemide and 27% by 1 microM acetylcholine. In the presence of Ca2+, the ionophore (10(-5) M) reduced tracer uptake 36% and prevented further effects of either acetylcholine or furosemide. Both acetylcholine and A23187 caused a rapid net efflux of 36Cl from tracer-preloaded acini in Ca2+-containing medium (37% and 20%, respectively). When Ca2+ was omitted from the incubation medium, basal 36Cl uptake in the absence of added test substance was the same as in Ca2+-containing medium but was not affected by acetylcholine, while it was still reduced 29% by furosemide. Addition of acetylcholine to preloaded acini in Ca2+-free medium caused only a transient and unsustained 36Cl efflux but subsequent addition of Ca2+ produced a 36% reduction in tracer content. The ionophore caused a net 36Cl efflux in Ca2+-containing medium (24% decrease in 36Cl content) but had no effect in Ca2+-free medium. Subsequent addition of Ca2+ resulted in a 27% net efflux of tracer. The calmodulin inhibitor trifluoperazine caused a 14% increase in 36Cl uptake but did not cause 36Cl efflux from preloaded cells or modify acetylcholine induced efflux of tracer from these cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099265 TI - Journal of Infection Control Nursing. Scratching the surface. PMID- 3099264 TI - The effect of drugs on mitochondrial DNA synthesis can be tested in isolated synaptosomes. PMID- 3099266 TI - Cost-effective quality. PMID- 3099267 TI - Intravenous immunoglobulin for prevention of sepsis in preterm and low birth weight infants. AB - The effect of an intravenous polyvalent immunoglobulin preparation given prophylactically to prevent neonatal sepsis was tested in preterm and low birth weight infants. Infants matched for gestational age, sex and birth weight (+/- 250 g) were randomly allocated into 3 groups of 50 each, one group (Group C) being used as control. Group A received Intraglobulin (Biotest Pharma, West Germany), 120 mg/kg intravenously, within 2 to 4 hours of delivery; Group B received the same on days 1 and 8. The control group received no immunoglobulin. The frequency of infection and serum immunoglobulin concentrations were determined in each group. Infection rate in the control group was 16% (8 of 50) while in each of the treated groups it was 4% (2 of 50) (P less than 0.005). The immunoglobulin concentrations achieved in the treated group were significantly higher than the control group. No adverse effect of the therapy was noted during the study and at a 6-month follow-up. It is suggested that in nurseries where the infection rate is high, prophylactic intravenous polyvalent immunoglobulin therapy for the preterm and low birth weight infants may provide protection from infection. PMID- 3099268 TI - Comparison of oral cephalosporins with penicillin therapy for group A streptococcal pharyngitis. AB - The purpose of the study was to compare the efficacy of cefaclor with that of penicillin V potassium (penicillin) in patients with Group A streptococcal pharyngitis. One hundred four children with pharyngitis and serologically confirmed Group A streptococci were randomly treated with cefaclor or penicillin using a mean dosage of 20 mg/kg/day for 10 days. The difference in failure rates (14% for 51 cefaclor- and 30% for 53 penicillin V-treated patients) was statistically significant (P = 0.04). In four earlier similar studies I found that cephaloglycin, cephalexin (two studies) and cefatrizine were consistently but not significantly more effective than penicillin therapy. When the data from the five studies are combined the difference between the failure rates (11% for 263 oral cephalosporin- and 23% for 230 penicillin-treated patients) becomes highly significant (P less than 0.001). The 95% confidence interval for the odds for treatment failure are 2.4 times greater for patients receiving penicillin than for those receiving one of the oral cephalosporins. On the basis of these data I conclude that the oral cephalosporins appear to be more effective than penicillin for therapy of Group A streptococcal pharyngitis. PMID- 3099269 TI - Lack of effect of Lactobacillus on gastrointestinal bacterial colonization in premature infants. AB - Studies were carried out on premature infants in the neonatal intensive care unit to determine the effect of feeding of lactobacilli on colonization of the gastrointestinal tract by antibiotic-resistant gram-negative enteric organisms. Thirty premature infants were matched by birth weight and gestational age, randomized and fed double blind either lactobacilli-containing formula or non lactobacilli-containing formula within 72 hours of delivery. The two study groups were screened weekly by culture for stool lactobacilli, for gram-negative bacteria and for antibiotic resistance of these bacteria. Lactobacilli were cultured from the stools of 13 of 15 patients receiving lactobacilli and from 3 of 15 patients not receiving lactobacilli (P less than 0.001). Gram-negative enteric organisms were isolated during 40 of the 86 weeks (47%) of hospitalization for patients receiving lactobacilli and during 28 of 57 weeks (49%) for patients not receiving lactobacilli. There was no significant difference between the study groups in the number of resistant organisms or in the proportion of resistant organisms per gram-negative enteric isolates (4 of 40 vs. 0 of 28). These results suggest that facultative gram-negative enteric bacterial colonization, with either total or aminoglycoside-resistant strains, is not decreased by oral feedings of Lactobacillus acidophilus in premature infants. PMID- 3099271 TI - Use of polydioxanone absorbable monofilament sutures in orthopedic surgery. AB - The safety and efficacy of polydioxanone absorbable monofilament sutures was documented in 57 orthopedic surgery patients (32, dyed sutures; 25, undyed sutures), 55 of whom were followed for at least 42 days postoperatively. The other two patients were lost to follow up prior to 42 days. The final clinical outcome was excellent in all completed study subjects. No suture-related adverse effects were reported. Both dyed and undyed sutures were consistently better than surgical gut with respect to pliability, strength, ease of passage, ease of tying, fraying, knot security, and overall handling. Intraoperative visibility of dyed polydioxanone sutures was consistently superior to that of surgical gut. The visibility of undyed sutures was rated better than surgical gut in 16 cases, equal in 8, and worse in 1. Both the overall handling of the polydioxanone monofilament sutures and performance as it affected wound healing were significantly superior to those of surgical gut. PMID- 3099270 TI - Protein kinase C potentiates corticotropin releasing factor stimulated cyclic AMP in pituitary. AB - The hypophysiotrophic hormone corticotropin releasing factor (CRF) stimulates the anterior pituitary corticotroph to export stress hormones such as adrenocorticotrophic hormone (ACTH). In rat anterior pituitary cells, CRF-induced elevation of cyclic AMP was profoundly potentiated (by an order of magnitude) by stimulators of protein kinase C. This effect occurred within minutes, was concentration dependent, and exhibited the appropriate pharmacological specificity to attribute the effects to protein kinase C. Phorbol myristate acetate (PMA), phorbol dibutyrate (PDB) and teleocidin were active with appropriate EC50's, while 4-alpha-PMA was inactive. PMA and PDB were also ACTH secretagogues in their own right. We suggest that protein kinase C can modulate CRF receptor coupling to the adenylate cyclase holoenzyme in anterior pituitary cells. PMID- 3099272 TI - [Porous tarflen as a possible membrane material for membrane blood oxygenators. III. O2 and CO2 transport in the system modeling an artificial lung]. AB - Diffusional examinations of tarflen porous barriers of home make and porous teflon membranes of American make as well as selected nonporous membranes were performed in a system: O2--barrier--water + CO2, in order to evaluate the influence of aqueous phase on O2 and CO2 transport rate through barriers listed above. It was found that the effectiveness of O2 and CO2 exchange through the porous barriers in the examined system is controlled by O2 transport through the boundary water layer in contradistinction to the nonporous membranes. The effect of reduction of O2 and CO2 transport through the porous barriers, caused by the aqueous phase was noted. The higher the water pressure on a barrier the larger the effect is. Considerable water permeability of porous barriers as compared to that of nonporous membranes was stated. The results of the performed examinations indicate the usefulness of porous tarflen materials as a membrane material in membrane oxygenators of blood. PMID- 3099273 TI - Objective relief of vasospasm by glyceryl trinitrate in secondary Raynaud's phenomenon. AB - An objective response to topical glyceryl trinitrate was shown by digital plethysmography in a study of 17 patients with Raynaud's phenomenon. Improvement was significant (P less than 0.005) in those in whom the disease was secondary to an underlying connective tissue disorder. The response suggests that the effect of this drug is mediated locally. PMID- 3099274 TI - Pneumoperitoneum. PMID- 3099275 TI - Dysarthria and visual hallucinations due to flecainide toxicity. AB - A 65 year old man with recurrent ventricular tachyarrhythmias post myocardial infarction developed dysarthria and visual hallucinations due to flecainide toxicity. A readily available assay is required for estimating serum flecainide levels in patients with diminished renal or hepatic function or failed arrhythmia suppression. PMID- 3099276 TI - Evaluation of the efficacy of flecainide acetate in the treatment of ventricular premature contractions. PMID- 3099277 TI - Influence of virginiamycin on broilers fed four levels of energy. AB - An experiment was conducted with broiler chicks to determine the influence of Virginiamycin on chicks fed diets with four levels of energy. Addition of the Virginiamycin to the diet resulted in significantly improved body weight and feed efficiency at all levels of energy. The greatest improvement was obtained at the lowest level of energy. Addition of Virginiamycin to the diet decreased the energy required to produce a unit of body weight. PMID- 3099278 TI - Stimulation of ovine choriomammotrophin release, in vitro, by phospholipase C. AB - Phospholipid metabolites have previously been implicated in receptor-mediated stimulation of protein hormone secretion. As the factors which regulate the release of choriomammotrophin remain to be elucidated, we investigated the potential involvement of phospholipase C-induced phospholipid metabolism in the release of this placental hormone. Phospholipase C (PLC) caused a dose-dependent release of choriomammotrophin from ovine placenta, incubated in vitro. At a concentration of 0.2 units/ml (0.25 microgram protein/ml), PLC caused the release of choriomammotrophin from placental tissue to approximately double that observed in control incubations (7.08 +/- 0.4 micrograms/50 mg/h and 3.26 +/- 0.3 micrograms/50 mg/h, respectively). PLC treatment did not significantly alter plasma membrane permeability, as indicated by the release of lactate dehydrogenase and protein. PLC-stimulated release of oCM was completely abolished by incubation in calcium-free medium or by preincubation with the inorganic calcium-channel blocking agents cobalt chloride (4 mM) and lanthanum chloride (1 mM). The effects of PLC treatment on ovine choriomammotrophin (oCM) release were also inhibited by preincubation of placental tissue with inhibitors of arachidonic acid metabolism: ibuprofen (10(-5) M), naproxen (10(-4) M) or nordihydroguaiaretic acid (NDGA) 5 X 10(-6) M). These results suggest that the effects of PLC on the release of choriomammotrophin are mediated via metabolites of arachidonic acid. PMID- 3099279 TI - Evaluation of an Alaskan streptococcal control program: importance of the program's intensity and duration. AB - Prospective follow-up information from the throat culturing results of 1,653 Eskimo children in 12 Alaskan villages was used to evaluate the effect of duration and intensity of a streptococcal control program begun in 1971 while controlling for several other risk factors related to streptococcal colonization. Relative risks of colonization for each of the subsequent study years relative to the first year indicate that the risk of colonization decreased over the duration of the study by 42% in Year 2 to 55% in Year 4 (P less than 0.0001). Cost-cutting measures such as lengthening the time interval between routine throat cultures led to a 37% increase in the risk of colonization (P = 0.0002). A comparison of the number of cases of acute rheumatic fever during the 5-year period before the streptococcal control program with the number of cases during the 5-year program period showed that cases in villages with the program decreased from 11 to 0. In a similar group of comparison villages without the program, the number of cases decreased from 7 to 4. A benefit-cost study of the program indicates that benefit exceeds cost. These findings and the changes in the carriage of streptococcal organisms during the control program underscore the importance of such long-term programs with regularly scheduled culturing in high-risk populations of children. PMID- 3099280 TI - Cost analysis and time charge development via computer operating room statistics. PMID- 3099281 TI - Multisite phosphorylation of the alpha subunit of transducin by the insulin receptor kinase and protein kinase C. AB - The GDP-bound alpha subunit of transducin, but not the guanosine 5'-[gamma thio]triphosphate-bound one, undergoes phosphorylation on tyrosine residues by the insulin receptor kinase and on serine residues by protein kinase C. Holotransducin is poorly phosphorylated by the insulin receptor kinase and is not phosphorylated by protein kinase C. Neither holotransducin nor any of its subunits were phosphorylated by the cAMP-dependent protein kinase. That a given subunit of transducin undergoes multisite phosphorylation depending on the type of nucleotide bound to it or the nature of the kinase suggests that hormone dependent phosphorylation could provide a versatile mode for regulation of guanine nucleotide-binding protein (G protein) function. In particular, the findings that certain G proteins serve as substrates for both the insulin receptor kinase and protein kinase C implicate G proteins in playing a key role in mediating the action of insulin and ligands that act to activate protein kinase C. PMID- 3099282 TI - Identification of an activated c-Ki-ras oncogene in rat liver tumors induced by aflatoxin B1. AB - Weanling male Fischer rats were administered 40 intraperitoneal injections of aflatoxin B1 (25 micrograms per animal per day) over a 2-month period. This chronic dosing regimen resulted in the sequential formation of hyperplastic foci, preneoplastic nodules, and hepatocellular carcinomas in all of the animals treated. The presence of transforming DNA sequences was detected by formation of anchorage-independent foci after transfection of tumor-derived DNA in NIH 3T3 mouse fibroblasts. Transfection of genomic DNA isolated from individual tumors from eight animals resulted in specific transforming activities ranging from 0.05 to 0.2 foci per micrograms of DNA. Primary transfectant DNAs were analyzed by Southern blot hybridization with DNA probes homologous to c-Ha-ras, c-Ki-ras, and N-ras oncogenes. A highly amplified c-Ki-ras oncogene of rat origin was detected in transformants derived from tumors in two of the eight animals tested. There was no evidence to suggest the presence of c-Ha-ras or N-ras sequences in any of the transformants. Analysis of primary liver tumor DNA showed no Ki-ras DNA amplification when compared to control liver DNA samples. Increased levels of c Ki-ras p21 proteins were detected in 3T3 transformants containing activated rat c Ki-ras genes. The presence of c-Ki-ras sequences of rat origin capable of inducing transformed foci can be taken as evidence that the c-Ki-ras gene has been activated in the primary liver tumors. PMID- 3099283 TI - Alternative splicing generates two distinct Eip28/29 gene transcripts in Drosophila Kc cells. AB - The Drosophila Eip28/29 gene encodes two primary translation products, ecdysone inducible polypeptide (EIP) 28III and EIP 29III. When cells of the Kc cell line are treated with the steroid hormone ecdysone, the number of Eip28/29 transcripts and the synthesis of the various forms of EIP 28 and 29 increase rapidly. We have reported the sequence of the Eip28/29 gene and of its major transcript. Here we describe a minor or short-form transcript that is about 25% of the total Eip28/29 gene transcripts in both untreated and hormone-treated cells. This transcript is formed by the use of an alternative splice donor sequence 12 nucleotides upstream from the major donor site at the end of the second exon. Evidently the relative abundance of the two products is not hormonally regulated. The short form translation product should lack only an internal dibasic tetrapeptide. The long and short forms probably represent distinct mRNAs for EIP 28III and EIP 29III, respectively. PMID- 3099284 TI - New RNA polymerase sigma factor under spo0 control in Bacillus subtilis. AB - In Bacillus subtilis transcription of spoVG is activated within minutes after the initiation of sporulation. Mutations in several spo0 genes prevent the activation of spoVG transcription. We have found a sigma-like protein that is capable of directing core RNA polymerase to use the spoVG promoter in an in vitro run-off transcription assay. This sigma-like protein was not found to be associated with RNA polymerase in a spo0A or spo0B mutant but was present in a spo0H mutant. We suggest that one role of the spo0A gene product in transcription of spoVG is the modulation of RNA polymerase activity by this sigma-like protein. PMID- 3099285 TI - Nucleotide sequence, tissue-specific expression, and chromosome location of human carbonic anhydrase III: the human CAIII gene is located on the same chromosome as the closely linked CAI and CAII genes. AB - The carbonic anhydrases (CA) are a class of metalloenzymes that catalyze the reversible hydration of carbon dioxide. The genes for the carbonic anhydrase isozymes are members of a multigene family that are differentially expressed in a number of cell types. We have isolated a full-length representative of a CAIII mRNA transcript from an adult human muscle cDNA library, and we present the complete nucleotide sequence of this cDNA clone. RNA blots demonstrate that CAIII messages can be detected in a variety of cell types but that high-level expression is limited to human fetal and adult skeletal muscle and to rodent slow skeletal muscle and liver. In addition, we have used a panel of human-mouse cell hybrids to localize the human CAIII gene to chromosome 8. Previous reports have established the CAI and CAII isozyme genes to be closely linked on chromosome 8, and the assignment of the CAIII gene to the same chromosome raises the possibility that these genes may all be linked at a single complex locus. PMID- 3099286 TI - Mutational analysis of the immunoglobulin heavy chain promoter region. AB - Complete immunoglobulin heavy chain (IgH) genes (gamma and mu) containing the intronic IgH enhancer and mutations in the upstream promoter region were constructed in vitro and introduced into murine J558L myeloma cells by protoplast fusion. S1-nuclease mapping experiments demonstrated that IgH gene expression was extremely sensitive to mutation in an upstream region containing the octanucleotide sequence ATGCAAAT. Significant IgH mRNA levels were detected in RNA from cells transfected with IgH gene constructs in which all upstream sequences on the 5' proximal side of this element were deleted. Similar results were obtained using the precise inverse of the IgH octamer, which is found in the upstream promoter region of immunoglobulin light chain genes. Deletion of the IgH octamer, or point mutation of adenine to guanine at position 6, resulted in the loss of correctly initiated IgH mRNA. A DNA binding factor from J558L nuclear extracts was identified that appeared to recognize the octamer on the basis of differential binding to homologous restriction fragments containing the various mutations and that bound preferentially with octamer DNA fragments derived from functional relative to nonfunctional IgH constructs. Collectively, these data suggest that the octamer element contains residues that are critical to accurate immunoglobulin gene transcription and that may serve as part of a recognition locus for nuclear factors important to B-cell-specific immunoglobulin expression. PMID- 3099287 TI - Intracytoplasmic phosphorylation sites of Tac antigen (p55) are not essential for the conformation, function, and regulation of the human interleukin 2 receptor. AB - Tac antigen, the receptor for human interleukin 2 (IL-2), contains in its intracytoplasmic region a serine residue (Ser-247) that is seemingly the predominant site of protein kinase C-mediated phosphorylation. A number of studies on growth factor receptors have suggested the importance of phosphorylation in receptor structure, function, and regulation. In this study, we generated site-directed mutations in the Tac antigen cDNA to generate mutant receptors in which Ser-247 or Thr-250, a probable site of minor phosphorylation, was replaced with another amino acid that is not accessible to phosphorylation. Study of the expression of these mutant genes in a T-lymphoid cell line has provided no evidence as to the essential role of the above-mentioned residues in determining the degree of receptor affinity, its ability for signal transduction, and phorbol ester-mediated regulation of the receptor. Our results strongly suggest the existence of an IL-2 receptor "complex" in which the Tac antigen is associated with another molecule(s) that is involved in receptor structure, function, and regulation. PMID- 3099288 TI - Monocyte migration explains the changes in macrophage arachidonate metabolism during the immune response. AB - The profile of arachidonic acid metabolites in resident peritoneal macrophages is distinctly different from the profile of macrophages isolated after an acute bacterial infection. The latter produce decreased prostaglandins E2 and I2 and leukotriene C4 while conserving the synthesis of thromboxane A2. We show here that the initial changes in peritoneal macrophage arachidonate metabolism during the immune response appear to be the result of the large influx of blood monocytes, which have a characteristic metabolism distinct from resident macrophages. We demonstrate that the initial decrease in peritoneal macrophage arachidonate metabolism and the increase in macrophage numbers occur simultaneously after infection with Listeria monocytogenes. Also the macrophage arachidonate metabolism seen at the height of the peritoneal cellular influx is the same as that of purified blood monocytes. Both Listeria peritoneal macrophages and blood monocytes produce equal or greater quantities of thromboxane A2 relative to prostaglandins I2 and E2 or leukotriene C4 whereas resident cells produce 1/10 to 1/25 as much thromboxane A2 compared to the other products. Furthermore, the changes in peritoneal macrophage arachidonate metabolism in response to Listeria infection do not occur if the influx of blood monocytes is stopped by irradiating the mice prior to infection implying that the cellular influx is necessary to see the changes in arachidonate metabolism. Finally, activation of peritoneal macrophages, measured as an increase in Ia expression, occurs 36 hr after the influx of monocytes from the blood and the resultant shift in arachidonate metabolism during Listeria infection. PMID- 3099289 TI - Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex. AB - The interleukin 2 (IL-2) receptor system plays a key role in the T-cell immune response. Although IL-2 binding was reported to be restricted to the Tac peptide, we have identified an IL-2 binding peptide that does not react with anti-human IL 2 receptor monoclonal antibodies, including anti-Tac on MLA 144, a gibbon ape T cell line. The MLA 144 cell line expressed 6800 IL-2 binding sites per cell with a low (Kd = 14 nM) affinity for human recombinant IL-2. Using cross-linking methodology, we demonstrated that the IL-2 binding peptide on MLA 144 is larger (Mr 75,000) than the Tac peptide, which has a Mr of 55,000. An IL-2 binding peptide of similar size (Mr 75,000) was also identified in addition to the Tac peptide (Mr 54,000-57,000) on Hut 102, a human T-cell lymphotrophic virus I induced T-cell leukemia line, and phytohemagglutinin-activated normal human and gibbon ape lymphoblasts. Anti-Tac antibody did not block the binding of 125I labeled IL-2 to MLA 144 cells. However, this antibody abolished the binding of 125I-labeled IL-2 not only to the Tac peptide on Hut 102 cells and normal lymphoblasts but also to the Mr 75,000 IL-2 binding peptide, suggesting that this latter peptide is associated with the Tac peptide to form the high-affinity IL-2 receptor complex. PMID- 3099290 TI - Long-term modulation of Ca2+-stimulated autophosphorylation and subcellular distribution of the Ca2+/calmodulin-dependent protein kinase in the brain of Drosophila. AB - After prolonged visual adaptation of Drosophila, dramatic long-term changes of in vitro phosphorylation of a 50-kDa brain protein that is identical to the Ca2+/calmodulin-dependent protein kinase (EC 2.7.1.37) can be measured in isolated heads. By selective receptor cell desensitization in blue light, subcellular distribution of the 50-kDa kinase in fly brain is modified, and Ca2+ stimulated in vitro phosphorylation is increased. Concomitantly the 50-kDa kinase is translocated by in vitro phosphorylation from the membrane-cytoskeleton complex into the cytoplasm. After adaptation, association of the enzyme to the membrane shows long-term modification. In yellow light, which reverts receptor cell adaptation within seconds, the changes in kinase activity and distribution remain for about 2 hr, corresponding to the duration of behavioral modification induced by blue light. Reducing protein synthesis with cycloheximide inhibits the induction of behavioral modification as well as the prolonged modulation of the 50-kDa kinase by blue light. From our simple assay to measure biochemical changes induced in the intact organism by sensory stimulation, we propose that Ca2+/calmodulin-dependent kinase II is involved in long-term modulation of synaptic transmission. PMID- 3099291 TI - Homologous down-regulation of the insulin receptor is associated with increased receptor biosynthesis in cultured human lymphocytes (IM-9 line). AB - Cultured IM-9 lymphocytes were preincubated with 1 microM insulin, a condition resulting in a 56% reduction in cell surface insulin receptors. Cellular proteins were then metabolically labeled, and the radioactivity incorporated into the insulin proreceptor and receptor mature subunits was measured over a 4-hr chase period. As early as 30 min of chase, incorporation into the proreceptor was 28 +/ 6% higher in down-regulated cells than in control cells (mean +/- SEM, P less than 0.05). By 1 hr of chase, the difference reached 41 +/- 14% for the proreceptor and 84 +/- 28% for the alpha subunit (P less than 0.01); values returned to normal by 2 hr. At 4 hr of chase, labeling of the alpha subunit of down-regulated cells was diminished 36 +/- 9% below control (P less than 0.05). The increased biosynthetic rate of the proreceptor was more prominent when the chase medium contained 25 microM monensin, an inhibitor of processing of the proreceptor into mature subunits. Similar effects occurred whether [3H]mannose or [3H]lysine was used as biosynthetic marker. The effect was specific for the insulin receptor. These data demonstrate that insulin receptor homologous down regulation is associated with increased proreceptor biosynthesis and processing into mature subunits. This might represent a cellular mechanism compensating for insulin-induced receptor loss. PMID- 3099292 TI - Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer. AB - We describe a cell-lineage marking system applicable to the vertebrate nervous system. The basis of the technique is gene transfer using the retroviral vector system. We used Escherichia coli beta-galactosidase as a marker gene and demonstrate a high level of expression of this marker from the viral long terminal repeat promoter, with simultaneous expression of the Tn5 neo gene from the simian virus 40 early promoter. This expression has allowed us to detect individual infected cells histochemically. We applied this marking technique to the study of lineage relationships in the developing vertebrate nervous system, both in vivo and in culture. In the rat retina, we injected virus in vivo and histochemically identified clones of marked neural cells. In addition, we used this virus to infect cultures of rat cerebral cortex and have analyzed the clonal relationships of morphologically different neural cell types. The host range of the marking system extends to avian as well as mammalian species. Thus, this system should have broad applicability as a means of gene transfer and expression in the nervous system. PMID- 3099293 TI - Drastically increased expression of MYC and FOS protooncogenes during in vitro differentiation of chronic lymphocytic leukemia cells. AB - Chronic lymphocytic leukemia cells, representing a clonal population of resting B lymphocytes, were induced to differentiate into immunoglobulin-secreting lymphoblasts and plasmablasts by phorbol 12-myristate 13-acetate. The induction resulted in a rapid increase in the molar ratio of secreted/membrane-bound mu chain mRNA. Immunoglobulin secretion was preceded by a transition of the cells from the G0 to G1 phase of the cell cycle, as indicated by an increase in RNA and protein synthesis, and an overall increase in cellular RNA. The cells, however, became blocked in G1 and did not enter S phase. The expression of MYC and FOS was rapidly induced by the phorbol 12-myristate 13-acetate treatment. The induction of FOS preceded the shift in secreted/membrane-bound mu-chain mRNA molar ratio, while that of MYC occurred concomitantly with the shift, but prior to induction of total RNA synthesis and immunoglobulin secretion. MYC expression remained at a relatively high level during the whole differentiation process. It is thus concluded that a decline of MYC expression is not a prerequisite for differentiation of the chronic lymphocytic leukemia cells. This suggests that MYC expression may play a different role during differentiation of nonproliferating B cells than in the myelomonocytic cell lines HL-60 and U-937, where MYC expression has been reported to decrease during induced differentiation. The results also show that the expression of the MYC and FOS genes does not result in the transition of these cells into the S phase of the cell cycle. PMID- 3099294 TI - Evidence for high peptide alpha-amidating activity in the pancrease from neonatal rats. AB - A high peptidylglycine alpha-amidating mono-oxygenase (PAMase) activity has been measured in the pancreas of neonatal rats. A significant fraction of this activity is contained in the beta cells of the islets of Langerhans and is colocalized with thyrotropin-releasing hormone (TRH) and its precursor in secretory granules. The ontogenetic variation of PAMase activity in the pancrease parallels that of TRH concentrations, suggesting that this enzymatic activity is directly related to TRH biosynthesis. In addition, PAMase activity is able to generate TRH when incubated with less than Glu-His-Pro-Gly, a tetrapeptide present as a repetitive sequence in the TRH precursor. The perinatal evolution of the TRH precursor levels in the pancreas is similar to that of PAMase activity (unpublished results). Thus, the neonatal rat pancreas offers an endocrine model in which the levels of a neuropeptide precursor and an enzyme activity, involved in the posttranslational modification of this precursor, are similarly regulated. Our results suggest also that a fraction of PAMase activity may be produced outside of the beta cells and related to the biosynthesis of COOH-terminally amidated peptide(s) other than TRH. The ontogenetic changes in PAMase activity imply that the synthesis of this peptide(s) is high during the neonatal period, decreasing thereafter. PMID- 3099295 TI - Thymine-containing dimers as well as spore photoproducts are found in ultraviolet irradiated Bacillus subtilis spores that lack small acid-soluble proteins. AB - Dormant spores of a Bacillus subtilis mutant that lacks two major small, acid soluble spore proteins are very sensitive to UV irradiation, which in spores generates about half the amount of thymine-containing dimers formed by comparable irradiation of vegetative cells. Irradiation of mutant spores also produces spore photoproducts, but again only about one-half the amount formed in comparably irradiated wild-type spores. These findings suggest that the high UV sensitivity of the mutant spores is due to the production of pyrimidine dimers, which are not found in UV-irradiated wild-type spores, and that the high level of small, acid soluble proteins found in wild-type spores is directly involved in spore UV resistance by facilitating a conformational change in spore DNA, preventing pyrimidine dimer formation. PMID- 3099296 TI - Tumor necrosis factor inhibits MYC expression in HL-60 cells at the level of mRNA transcription. AB - Highly purified, recombinant human tumor necrosis factor type alpha (rTNF-alpha) exerts cytostatic activity on the human promyelocytic leukemic cell line HL-60. Between 4 and 10 hr after treatment with rTNF-alpha, HL-60 cells start to exhibit phagocytic activity, indicating the induction of a differentiation process, and show a marked decline in steady-state levels of MYC mRNA. In vitro transcription assays reveal that rTNF-alpha inhibits MYC gene expression at the level of transcription. rTNF-alpha has little or no effect on the half-life of MYC mRNA, indicating that the decreased MYC mRNA level is primarily due to reduced transcription, and the protein synthesis inhibitor cycloheximide does not prevent rTNF-alpha-mediated inhibition of MYC gene expression, suggesting that rTNF-alpha action is independent of de novo protein synthesis. In contrast to MYC, HLA-A, B, -C mRNA levels are slightly increased in rTNF-alpha-treated HL-60 cells. Recombinant interferon-gamma, which also enhances HLA gene transcription in HL-60 cells, fails to reduce MYC mRNA levels and lacks cytostatic activity. Attenuation of HL-60 cell proliferation occurs as a late response to treatment with rTNF alpha and thus may be secondary to both MYC inhibition and induction of cell differentiation. PMID- 3099297 TI - Induced mRNA stability in Bacillus subtilis. AB - We have investigated the induced stability of mRNA encoded by the ermC gene in Bacillus subtilis. Induction of ermC gene expression by erythromycin is known to occur at the translational level. We show that this induction is accompanied by an increase in ermC mRNA half-life from about 2 min to about 40 min. Induced stabilization of ermC mRNA occurs independently of induced translation. The regulatory sequences required for stability are promoter-proximal and can confer induced stability on large mRNAs having diverse 3' ends. Translation of the ermC leader peptide and ribosome-stalling in the leader peptide sequence are necessary for induced stabilization. PMID- 3099300 TI - Protein-energy malnutrition and risk of infection. PMID- 3099298 TI - Loss of platelet-derived growth factor-stimulated phospholipase activity in NIH 3T3 cells expressing the EJ-ras oncogene. AB - Data indicating that the 21-kDa protein (p21) Harvey-ras gene product shares sequence homology with guanine nucleotide-binding proteins (G proteins) has stimulated research on the influence(s) of p21 on G-protein-regulated systems in vertebrate cells. Our previous work demonstrated that NIH-3T3 mouse cells expressing high levels of the cellular ras oncogene isolated from the EJ human bladder carcinoma (EJ-ras) exhibited reduced hormone-stimulated adenylate cyclase activity. We now report that in these cells another enzyme system thought to be regulated by G proteins is inhibited, namely phospholipases A2 and C. NIH-3T3 cells incubated in plasma-derived serum release significant levels of prostaglandin E2 (PGE2) as determined by radioimmunoassay when exposed to platelet-derived growth factor (PDGF) at 2 units/ml; the levels of PGE2 released from EJ-ras-transfected cells are only 3% those of controls despite a similar basal (unstimulated) release from control and EJ-ras-transfected cells. The lack of PDGF-stimulated PGE2 release from EJ-ras-transfected cells is not due to a defect in the prostaglandin cyclooxygenase enzyme, since incubation of control cells and EJ-ras-transfected cells in 0.33, 3.3, or 33 microM arachidonate resulted in identical levels of PGE2 release. The lack of PDGF-stimulated PGE2 release from EJ-ras-transfected cells also does not result from the loss of functional PDGF receptors. EJ-ras-transformed cells bind 70% as much 125I-labeled PDGF as control cells and are stimulated to incorporate [3H]thymidine and to proliferate after exposure to PDGF. Moreover, this inhibition is not likely the result of a secondary cellular effect related to the transformed phenotype, since NIH-3T3 cells transformed by v-src released PGE2 at wild-type levels after exposure to PDGF. Determination of total water-soluble inositolphospholipids and changes in the specific activities of phosphatidylcholine in control and EJ-ras transfected cells demonstrated that PDGF-stimulated phospholipase C and A2 activities are inhibited in the EJ-ras-transfected cells. PMID- 3099299 TI - Correlations between development rates, enzyme activities, ribosomal DNA spacer length phenotypes, and adaptation in Drosophila melanogaster. AB - Selection for "fast" preadult development rate among the progeny of flies collected in a natural population of Drosophila melanogaster produced a line that developed more rapidly than a line selected for "slow" preadult development rate. Assays for enzyme activity levels showed that the activities of alpha glycerophosphate dehydrogenase, alcohol dehydrogenase, and malic enzyme were higher in the fast than in the slow line, but that the activity of superoxide dismutase was lower in the fast line. Differences in the frequencies of spacer length phenotypes of X chromosome-linked rRNA genes (rDNA), which developed between the lines during the selection process, are larger than can be explained on the basis of genetic drift alone. Long rDNA spacers had high frequency in the fast line; short spacers, in the slow line. We conclude that enzyme levels affected adaptation under the selective regimes imposed and that the different X linked rDNA spacer-length phenotypes are either adaptive in themselves or that they mark chromosomal segments carrying genes relevant to adaptation. PMID- 3099301 TI - Vitamin and essential trace element recommendations during intravenous nutrition: theory and practice. PMID- 3099302 TI - Update on dietary fat and cancer. PMID- 3099303 TI - Antagonism by thyrotropin-releasing hormone of brain temperature in response to pentobarbital in the rat: possible involvement of cholinergic mechanism. AB - The effects of thyrotropin-releasing hormone (TRH) on brain temperature in response to pentobarbital were examined in male rats. After intraperitoneal injection of pentobarbital sodium (55 mg/kg body wt), the rats were fixed stereotaxically and received intraventricular (ivt) injection of varying doses (0.03-30 nmol) of TRH and 17 nmol atropine. Following the injection of 3 nmol TRH, 100 nmol of carbocholine was administered in the same manner. A thermocouple microprobe was unilaterally placed in the midbrain reticular formation so that brain temperature was continuously monitored at room temperature. Brain temperature after pentobarbital injection progressively decreased. While ivt injection of saline did not affect this change in temperature, ivt administration of TRH produced a dose-dependent antagonism of the brain hypothermia induced by pentobarbital. Atropine injection also reversed the pentobarbital-induced decrease in brain temperature. Carbocholine injection led to a significant decrease in brain temperature in response to TRH administration. The present study indicates that brain TRH may play a pivotal role in brain thermoregulation and its mechanism may involve at least in part the central cholinergic pathway in the rat. PMID- 3099304 TI - Seasonal and photoperiod-induced changes in serum prolactin and pituitary responsiveness to thyrotropin-releasing hormone in the mare. AB - Experiments were conducted in the horse mare to study the effects of photoperiod and season on serum prolactin and pituitary responsiveness to thyrotropin releasing hormone (TRH). Increasing the photoperiod to 16 hr light:8 hr dark beginning in December (Experiment 1) and September (Experiment 2) increased serum prolactin, but the rate of increase was greater when the photoperiod treatment was initiated in September. In addition, TRH-induced prolactin secretion was found to be affected by season, in that pituitary secretion (net increase in prolactin and total prolactin secreted) was significantly greater in June compared with that of January (Experiment 3). These data suggest that in the mare, photoperiod plays an important role in controlling circulating levels of prolactin, but that in addition to photoperiod, other seasonally related factors, such as temperature, are involved in modulating the seasonal rhythm of serum prolactin. PMID- 3099305 TI - Effects of human carbonic anhydrase III (CA III) on synovial and muscle fibroblast glycosaminoglycan metabolism. AB - We investigated the ability of CA III, isolated from adult human skeletal muscle, to regulate cell growth and glycosaminoglycan (GAG) formation in connective tissue cells derived from various human tissues. Unlike muscle, dermal, and cartilage fibroblasts, synovial connective tissue cells were substantially activated by CA III and showed enhanced hyaluronic acid (HA) synthesis. Cell culture experiments showed that CA III induced a 2- to 11-fold increase in [14C]HA synthesis by human synovial fibroblasts (SF) in a dose-dependent manner (P less than 0.001); erythrocyte CA I and CA II were inactive. Exposure of SF and muscle fibroblasts to CA III also resulted in a 20-45% and 16-70% increased 35S incorporation into proteoglycans, respectively. When adult human skin and cartilage fibroblasts were studied in the presence of CA III, no differences in the level of DNA and GAG formation were noted. These latter cell types were clearly activated by a platelet (CTAP-III) growth factor. The potential physiological implications of these observations are discussed. PMID- 3099306 TI - Presence of acute phase changes in zinc, iron, and copper metabolism in turkey embryos. AB - Acute phase changes in trace mineral metabolism were examined in turkey embryos. An endotoxin injection resulted in increased concentrations of serum copper and liver zinc and decreased concentrations of serum zinc in embryos incubated either in ovo or ex ovo. Changes in zinc and copper metabolism occurred when endotoxin either was injected intramuscularly, into the amnionic fluid, or administered onto the chorioallantoic membrane. Unlike poults, embryos did not respond to an inflammatory challenge with decreased serum iron concentrations. Acute phase changes in embryo serum zinc and copper as well as liver zinc concentrations were similar to those in poults. Increased liver zinc concentrations were associated with increased zinc in metallothionein (MT). An injection of a crude interleukin 1 preparation into embryos resulted in similar increases in hepatic zinc and MT concentrations as an endotoxin injection, suggesting a role for this cytokine in mediating the acute phase changes in embryonic zinc metabolism. PMID- 3099307 TI - Biology of the T cell. PMID- 3099308 TI - Immunomodulation by ultraviolet irradiation. PMID- 3099309 TI - Treatment with anti-interleukin-2 receptor monoclonal antibody. PMID- 3099310 TI - Differential effects of diuretics on eicosanoid biosynthesis. AB - The selective influences of hydrochlorothiazide (HCT), furosemide (FUR), spironolactone (SPI) and indapamide (IND) on arachidonic acid (AA) metabolism were assessed in sheep seminal vesicle and in human platelet microsomes. All four compounds augmented the synthesis of prostaglandins (PGs) D2 (HCT,FUR), E2 (SPI) and I2 (FUR,IND), probably through facilitated reorientation of endoperoxide biotransformation. With the exception of HCT, the other drugs also suppressed the production of thromboxane A2 (IND greater than SPI greater than FUR); lipoxygenase formation of hydroxyeicosatetraenoic acid was also enhanced by SPI and IND. The antihypertensive efficacy of these diuretics could, in part, be related to their selective effects on AA metabolism which favor the net formation of depressor PGs. PMID- 3099311 TI - Increase in the formation of cyclooxygenase and lipoxygenase products in kidneys of adrenalectomized rats. AB - The effect of adrenalectomy on the formation of cyclooxygenase and lipoxygenase products from [1-14C]-arachidonic acid in rat kidneys after incubation with the Calcium-ionophore A23187 has been determined. The metabolites were isolated by HPLC. The main components formed are PGD2, PGE2, PGF2 alpha, LTB4, 5,12 di-HETE and 5-, 12- and 15-HETE. After adrenalectomy, an increase occurs in the formation of PG and LT, which is highest in that of PGD2 and 12-HETE. These effects are most probably related to a diminished formation or inactivation of lipocortin in adrenalectomized animals, a glucocorticosteroid induced peptide with phospholipase A2 inhibitory activity. PMID- 3099312 TI - The effects of cyclooxygenase inhibition on chemiluminescence and aggregation in sheep neutrophils. AB - Antiinflammatory actions of cyclooxygenase inhibitors may be related to inhibition of the synthesis and release of prostaglandins and thromboxane or to nonspecific actions of particular drugs. The role of cyclooxygenase products of arachidonic acid was studied in two leukocyte functions, free radical release and aggregation, after complement activation. Dose response curves were constructed after treatment with meclofenamate or ibuprofen. To differentiate between effects on free radical release from complement activated neutrophils and scavenging free radicals, additional experiments were made with a cell free system to generate free radicals. Both drugs inhibited complement initiated neutrophil chemiluminescence in a dose dependent manner. Meclofenamate acted primarily as a scavenger while ibuprofen inhibited free radical release. Neither drug had any inhibitory effects on complement induced leukocyte aggregation. PMID- 3099314 TI - Inhibition of eicosanoid formation by prazosin in the rabbit renal cortex. AB - The influence of the oral administration of prazosin (an alpha 1-adrenergic blocker) and propranolol (a beta-adrenergic blocker) on eicosanoid formation in renal cortices and papillae was evaluated in rabbits maintained on a high cholesterol diet. Rabbit renal microsomal fractions were incubated with radiolabeled arachidonic acid (AA) and glutathione (GSH) and the levels of metabolites were determined by thin layer chromatography (TLC), autoradiography and reverse phase-high performance liquid chromatography (RP-HPLC). Rabbits on a high cholesterol diet showed no significant differences in total eicosanoid production compared to rabbits on a normal diet. Prazosin was found to significantly inhibit the formation of all eicosanoids in the renal cortex. In contrast, propranolol had no such inhibitory effect in the renal cortex. Neither drug had a significant effect on eicosanoid formation in the renal papilla. While oral administration of prazosin effectively inhibited the formation of all eicosanoids in the cortex, the addition of prazosin in vitro at physiological concentrations showed no such effect. These findings may have reflected alpha receptor mediated event(s) which resulted in an alteration in eicosanoid formation in the kidney, suggesting an interaction between the sympathetic nervous system and the AA cascade. PMID- 3099313 TI - Specificity of PGE2 analogs interaction between food intake and antisecretory effect. AB - We evaluated the degree of acid suppression that occurred when enprostil, a dehydro-prostaglandin E2 (PGE2) methyl ester analog, was administered before (anti-cibum AC) or after a meal (post-cibum PC). A double-blind, randomized, single-dose, parallel-group design compared enprostil, 35 mcg, 25 min AC or 5 min PC, with placebo AC or PC in 30 healthy adults. Enprostil or placebo was administered at time 0 and a standard beef test meal was ingested at 25 min, followed 5 min later by enprostil or placebo. A second test meal was consumed at 210 min. Intragastric titration was performed from 30 to 390 min. Subjects receiving enprostil-AC or enprostil-PC secreted less (P less than 0.05) acid compared to placebo; however, the antisecretory effects of enprostil-AC or enprostil-PC were similar throughout the duration of study. Minor adverse reactions were present in 13/30 subjects and confined to those receiving enprostil. In contrast to the previously reported potentiation of trimoprostil, a trimethyl-desoxy-PGE2 analog, antisecretory activity by food, enprostil-PC did not result in more prominent or prolonged suppression of gastric acid secretion than enprostil-AC. There is an apparent specificity of different oral PGE2 analogs with regard to their antisecretory activity in the presence or absence of food. PMID- 3099315 TI - In vitro assessment of mononuclear leukocyte aggregation in response to sodium arachidonate and calcium ionophore A23187: comparison with polymorphonuclear leukocytes. AB - The effects of ionophore A23187 and sodium arachidonate (AASS) on mononuclear leukocyte (MNL) aggregation were evaluated and the results compared to those obtained with similarly challenged polymorphonuclear leukocytes (PMN). MNL aggregated in response to both ionophore A23187 (8-40 microM f.c.) and AASS (0.05 0.5 mM f.c.) and the response was comparable to that of similarly challenged PMN. The AASS induced aggregation of the two leukocyte subpopulations was inhibited by the presence of bovine serum albumin (BSA) in the incubation media and by calcium exogenously added. In contrast, this cation stimulated ionophore induced aggregation. When PMN and MNL aggregation was induced by AASS, a marked release of lactic dehydrogenase (LDH) was detected. The thromboxane-synthetase inhibitor UK 37248, inhibited both leukocyte aggregation and LDH release. When the response of leukocytes from male and female subjects was compared, in terms of aggregation, it appeared that the response of PMN from female volunteers was higher than that of PMN isolated from male donors, whereas no sex-related difference was detected when MNL aggregation was evaluated. PMID- 3099316 TI - Effects of leukotriene D4 and antagonists of arachidonic acid metabolism and calcium entry on guinea pig tracheal muscle responsiveness. AB - We studied the effects of antagonists of arachidonic acid metabolism and calcium entry on the responsiveness of airway smooth muscle to acetylcholine (ACh), potassium and norepinephrine. Responsiveness in vitro was assessed by measuring isometric contraction of guinea pig trachealis muscle upon chemical stimulation. We found that indomethacin potentiated the response of airway muscle to ACh and KCl, but not to norepinephrine. The indomethacin-induced potentiation observed was inhibited by both BW 755C and nifedipine. As occurred with indomethacin pretreatment, we also found that a noncontractile concentration of leukotriene D4 (LTD4) potentiated the responsiveness of tracheal muscle to both ACh and KCl. Our data suggest that indomethacin- and LTD4-potentiation of guinea pig airway muscle responsiveness to certain bronchoconstrictors may be mediated, at least in part, by enhanced extracellular Ca++ entry. PMID- 3099317 TI - Protection by two ginkgolides, BN-52020 and BN-52021, against guinea-pig lung anaphylaxis. AB - Interference between the ginkgolides BN-52020 and BN-52021 and the effects of PAF acether on the cardiovascular and pulmonary functions of guinea-pigs has been studied. BN-52020 (ED50 = 1.1 mg/kg i.v.) and BN-52021 (ED50 = 0.78 mg/kg i.v.) inhibit bronchospasm, hypotension and concomitant generation of TXA2-like activity induced by PAF-acether in anaesthetized guinea-pigs. This protecting activity is specific against PAF-acether since the two ginkgolides do not affect bronchoconstriction, hypotension and TXA2-like activity in the circulating blood due to Histamine, Acetylcholine and LTC4. BN-52021 reduces in a concentration dependent way the formation of TXB2 caused by PAF-acether in guinea-pig perfused lungs without interference with the effect of Histamine, LTC4 and Arachidonic acid on these tissues. Using actively sensitized (Ovalbumin) guinea-pigs BN-52020 (ED50 = 2.45 mg/kg i.v.) and BN-52021 (ED50 = 1.71 mg/kg i.v.) protect the animals from lethal immunological reaction suggesting that PAF-acether must play a role in the expression of anaphylactic bronchoconstriction and hypotension. The present results indicate that BN-52021 and in a lesser extent BN-52020, which are neither bronchodilators nor cyclooxygenase inhibitors, display a selective antagonistic activity against PAF-acether and may have potential therapeutical implication in asthma. PMID- 3099318 TI - Hormones of the hypothalamic-pituitary-thyroid axis: a psychoneuroendocrine perspective. AB - Although relationships between hormones of the hypothalamic-pituitary-thyroid (HPT) axis and behavior have been suspected for more than two centuries, there existed no framework within which they could be understood. It now appears that disturbances in the HPT-axis have more to do with affective state than with any other aspect of mentation, save possibly cognition. First, depression is the most frequently observed psychiatric symptom in patients suffering from hypothyroidism. Second, approximately 30% of euthyroid patients with major depression show a blunted, i.e., attenuated TSH response after TRH administration. Third, it is now well established that a small dose of thyroid hormone will accelerate the antidepressant effect of tricyclic antidepressants (TCA) in women, and convert TCA non-responders into responders in both sexes. Fourth, administration of TRH may induce an increased sense of well-being and relaxation in some patients and healthy volunteers. However, little is known about the pathophysiologic mechanism whereby evocative emotional factors express their effect on the HPT axis, or whereby thyroid gland alterations express their behavioral effects. Longitudinal, prospective studies of both patients with thyroid disease and patients with depression (through close collaboration between endocrinology and psychiatry) are most likely to separate cause and effect in most instances. PMID- 3099319 TI - Starvation and respiratory rhythmic behavior in groups of light-dark synchronized Sprague-Dawley rats. AB - Twenty adult male SPF Sprague-Dawley rats, grouped by 5 and synchronized by a light (L)-dark (D) 12:12 alternation, were deprived of food and water for 7 days; 20 other rats were taken as controls. Continuous measurement of emitted carbon dioxide (VCO2), which was taken as an index of respiratory and metabolic exchanges, shows that starvation significantly (p less than 0.001) decreases the amplitudes of the circadian VCO2 rhythms (by 42.5% during L and 35.6% during D) and also the L----D photic VCO2 responses (by 9.2%; p less than 0.05). Concerning ultradian rhythms of mean and great periods (40 min less than tau less than 24 hr), food and water suppression diminishes their amplitudes (by 58.4% in L and 32.4% in D) and changes their phases (by a 1.29 radian advance in L and a 0.68 radian delay in D). Rats recovered their prestarvation circadian and ultradian VCO2 rhythms 6-7 days after food and water had been given back to them. PMID- 3099320 TI - [Epileptic seizures in multiple sclerosis]. AB - Starting from informations in the literature, the authors deals with eight own cases, suffering from clinically certain multiple sclerosis and showing, as a further sign, epileptic seizures. Compared to the total of patients, these eight cases represent 1.78 p.c. of all patients treated for multiple sclerosis in this clinic. The features of seizures, frequency and dynamics of occurrence are referred to. The authors point out that it is necessary to differential between epileptic seizures and non-epileptic attacks, and they draw attention to the fact that here are difficulties with regard to differential diagnosis if epileptic seizure appears as a initial symptom of multiple sclerosis. PMID- 3099321 TI - [The assessment of disability in epileptic patients]. AB - Report is given concerning 16 epileptics in whom annuity could be suspended. Types of seizures did not differ from those analysed in a formerly study of further invalid epileptics. On the contrary, the beginning of treatment was very soon after manifestation of disease, and the treatment was in the hand of neuropsychiatrists with mostly good or very good attention. Improvement could be obtained mainly by decrease of seizure frequency of freedom from seizures, and after few years invalidity could be annulled. PMID- 3099322 TI - [Significance of the EEG for the prognosis of therapy in adult epileptic patients]. AB - The importance of EEG findings regarding prognosis of therapy and relapses of epilepsies is controversally discussed in the literature. On the basis of 495 patients being in attendance for many years there were some important indications for prognosis, for instance 59 percent of the patients with normal EEG at all times during the cours attained freedom from seizures for at least five years. The best possibilities for differentiation followed from EEG features during medication, especially from degree od disturbances of background activity. Only 13 percent of patients with more than slight disturbances in resting EEG remained seizure free for a long time. Also as a distinctly unfavourable sign proved the combination of generalized and focal epileptiform pattern. PMID- 3099323 TI - Maintenance phenelzine treatment of major depression: an interim report. PMID- 3099324 TI - Possible respiratory abnormalities in panic disorder. PMID- 3099325 TI - A cutaneous disorder (Darier's disease) evidently exacerbated by lithium carbonate. PMID- 3099326 TI - Mutation induction in spores of Bacillus subtilis by accelerated very heavy ions. AB - Mutation induction (resistance to sodium azide) in spores of Bacillus subtilis was investigated after irradiation with heavy ions from Neon to Uranium with specific particle energies between 0.17 and 18.6 MeV/u. A strong dependence of the mutation induction cross section on particle charge and energy was observed. From the results it was concluded that mutation induction in bacterial spores by very heavy ions is mainly caused by secondary electrons. PMID- 3099328 TI - The barium enema scout film: cost effectiveness and clinical efficacy. PMID- 3099327 TI - Relationship between heat sensitivity and polyamine levels after treatment with alpha-difluoromethylornithine (DFMO). AB - Alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, was used to study the effect of polyamine depletion on delayed heat sensitization in Chinese hamster ovary cells (CHO). The cells were treated with 1 or 10 mM DFMO for 8 or 48 h and then given a single heat treatment (43 degrees C, 90 min) at intervals up to 150 h after DFMO addition. Cellular survival, DNA polymerase activity, and polyamine levels were measured. Delayed heat sensitization for cell lethality began 50-55 h (about two cell divisions) after addition of 10 or 1 mM of DFMO for 8 or 48 h, respectively; i.e., cell survival of heated control cells was about 10(-1), but decreased to 10(-4)-10(-5) in heated DFMO-treated cells by 100 h. During this same interval, delayed heat sensitization also was observed for loss of DNA polymerase beta activity (from 20% in cells heated without DFMO treatment to 7% in heated DFMO-treated cells), but none was observed for DNA polymerase alpha activity. Delayed heat sensitization disappeared at 120-130 h after DFMO addition, with survival of heated DFMO-treated cells returning to that for heated control cells. The onset of delayed heat sensitization occurred 30-40 h after intracellular levels of putrescine and spermidine were depleted by more than 95%; however, spermine levels were not lowered, and in some cases even increased. Levels of putrescine and spermidine increased 5-10 h before delayed heat sensitization disappeared. While putrescine reached 25% of control, spermidine exceeded control levels during this time. Furthermore, delayed heat sensitization could be reversed by adding 10(-3) M putrescine or 5 X 10(-5) M spermidine 85-95 h after DFMO addition; in both cases spermidine increased 5-10 h before the decrease in heat sensitization. Finally, neither delayed heat sensitization nor depletion of spermidine was observed in nondividing plateau-phase cells treated with DFMO, although putrescine was depleted. These results lead to the hypothesis that DFMO induced heat sensitization which occurs after inhibition of the synthesis of putrescine is secondary to the depletion of spermidine in some critical compartment of the cell or to a biochemical alteration. This depletion or biochemical alteration apparently occurs as the cells divide about two times after the intracellular levels of soluble spermidine have been depleted. PMID- 3099329 TI - [Self-nonself discrimination]. PMID- 3099330 TI - Gastric mucosal binding studies with enprostil: a potent anti-ulcer prostaglandin. AB - The potent antiulcer prostaglandin enprostil binds with high affinity to porcine gastric mucosal tissues. This binding is saturable, dissociable and displaceable by compounds with similar structures. Various characteristics of binding such as pH optimum and displacement potencies suggest that enprostil binds to mucosal PGE2 sites. Structure-activity and gastric mucosal binding relationships were also examined. PMID- 3099331 TI - Effects of superovulation, arachidonic acid or endometrium on release of prostaglandins and synthesis of proteins by bovine trophoblast. AB - This study was conducted in vitro to examine factors that may regulate prostaglandin release by bovine trophoblast and endometrial slices. Trophoblastic tissues and endometrial slices were recovered from superovulating and normally ovulating cattle on day 16 or 20 of pregnancy and incubated for 24 h. Release of PGF2 alpha and 13,14-dihydro-15-keto-PGF2 alpha (PGFM), and incorporation of [14C]-leucine into proteins were quantified and expressed per microgram DNA, which gives a measure of cellular activity. Activity of trophoblastic tissue for synthesizing protein was decreased (P less than .05) and for releasing PGFM was increased (P less than .05) on day 20 compared to day 16 of pregnancy. Neither superovulation nor day of pregnancy altered trophoblastic activity for releasing PGF2 alpha. Superovulation increased (P less than .05) endometrial release of PGF2 alpha. Endometrial release of PGF2 alpha was less (P less than .05) on day 20 than on day 16 of pregnancy. When arachidonic acid (0, 100, 200 or 400 micrograms) was added at the start of incubation, trophoblastic release of PGF2 alpha changed (P less than .05) quadratically with dose of arachidonic acid. When arachidonic acid was added 8 h after the start of incubation, trophoblastic release of PGF2 alpha increased linearly (P less than .01) with dose of arachidonic acid. Adding arachidonic acid to incubation medium did not affect trophoblastic or endometrial protein synthesis. Endometrial slices suppressed (P less than .05) trophoblastic protein synthesis and release of PGF2 alpha. Apparently, endometrium can modulate trophoblastic release of prostaglandins and synthesis of proteins in vitro, and trophoblastic tissue from superovulated cattle 16 or 20 days pregnant can be used to study trophoblastic synthesis of prostaglandins and proteins. PMID- 3099332 TI - Separation and quantification of prostaglandins E1 and E2 as their panacyl derivatives using reverse phase high pressure liquid chromatography. AB - Separation and quantification of prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2) were achieved using reverse phase high performance liquid chromatography (HPLC). Panacyl bromide (p-(9-anthroyloxy)phenacyl bromide) (PAB) derivatives of PGE2 and PGE1 were prepared. Reverse phase HPLC using a linear gradient of 56% to 80% acetonitrile in water containing 0.10% acetic acid gave baseline resolution of the two derivatives. A 3 um diameter particle, C18 column provided good resolution and reproducible recoveries. Human synovial tissue cells were incubated with the precursor fatty acids for PGE1 or PGE2 and stimulated with a crude Interleukin 1 (IL-1) preparation. Cells grown in the presence of dihomogammalinolenic acid (DGLA), the precursor for PGE1, made significantly more PGE1 than cells grown in control medium or in the presence of arachidonic acid, precursor for PGE2. PGE2 synthesis was reduced when DGLA was added to cells (resting or IL-1-stimulated). PMID- 3099333 TI - Cycloheximide reduces PGD2 or delta 12-PGJ2 cytotoxicity on NCG cells. AB - To study the precise mechanism of cytotoxic activity of PGD2 or delta 12-PGJ2 (a biologically active metabolite of PGD2), we examined the effect of various compounds on PGD2 or delta 12-PGJ2 cytotoxicity, using a human neuroblastoma cell line (NCG). Cycloheximide (CHM) specifically protected PGD2 cytotoxicity on NCG cells. When delta 12-PGJ2 was tested, CHM exhibited a similar rescue effect. Puromycin, mitomycin C, and alpha-amanitin did not affect PGD2 or delta 12-PGJ2 cytotoxicity. Emetine showed a variable and no consistent rescue effect CHM may have been active at the primary site where PGD2 or delta 12-PGJ2 exerts its cytotoxicity. This is the first report indicating that CHM reduces the cytotoxicity induced by PGD2 or delta 12-PGJ2. PMID- 3099334 TI - Antagonism by ETYA of the effects of leukotrienes on ileum and lung parenchymal strips independent of effects on arachidonic acid metabolism. AB - 5,8,11,14-Eicosatetraynoic acid (ETYA), a compound which inhibits both the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism, antagonized the contraction of segments of guinea-pig ileal longitudinal muscle produced by SRS-A (IC50 = 2.73 microM). This activity was unaffected by pretreatment of the tissues with 10 microM indomethacin. Phenidone, another mixed cyclooxygenase-lipoxygenase inhibitor, was inactive. FPL-55712, an SRS-A antagonist, was a very potent inhibitor (IC50 = 0.011 microM). BW755C and NDGA nonselectively inhibited the contractions of the guinea-pig ileal longitudinal muscle induced by SRS-A or histamine. ETYA antagonized the contraction of the guinea-pig ileal strip produced by 6 nM synthetic LTC4 (IC50 = 9.3 microM). FPL 55712 demonstrated an IC50 of 0.3 microM in a similar series of experiments. ETYA, 1, 3 or 10 microM did not inhibit the contractions elicited by 0.5 microM of histamine. This was not a tissue-selective effect since 100 microM ETYA antagonized the LTC4-induced contraction of the guinea-pig lung parenchymal strip preparation. These data demonstrate that ETYA antagonized the contractile effect of the leukotrienes on tissues from the gastrointestinal tract and lung. Furthermore, the inability of indomethacin or phenidone to inhibit the contractile response suggests that antagonism by ETYA may occur by a mechanism independent of cyclooxygenase and lipoxygenase enzymes. PMID- 3099335 TI - Effects of prostaglandins and arachidonic acid on baboon cerebral and mesenteric arteries. AB - Effects of prostaglandins (PGs) E1, E2, F2 alpha and I2 in a wide range of concentration were examined in mesenteric and cerebral arteries isolated from mature baboons. PGs E1, E2 and F2 alpha at low concentrations (10(-10) to 10(-7) M) elicited relaxation in helically cut strips of cerebral arteries precontracted with phenylephrine. In contrast, the PGs did not cause relaxation in the mesenteric artery. PGI2 (10(-9) to 10(-6) M) produced marked relaxation in both arteries. The EC25 for PGI2 in the mesenteric artery was significantly lower than that in the cerebral artery. During baseline conditions, cerebral arteries contracted in response to high concentrations (greater than 10(-7) M) of PGs E1, E2 and F2 alpha. In mesenteric arteries, a large contraction was induced by PGs F2 alpha and E2 but not by PGE1. Arachidonic acid (10(-6) M) produced an aspirin inhibitable relaxation in both arteries to a similar extent, so that the vasodilator PG(s) formed in the two different arterial walls appear to exert a similar relaxant action. Thus, the baboon mesenteric artery was more sensitive to PGI2 for the relaxant effect than was the cerebral artery, while PGs F2 alpha, E1 and E2 caused only a contraction in the mesenteric artery but both relaxation and contraction in the cerebral artery. PMID- 3099336 TI - Modulation of the 5-lipoxygenase activity of MC-9 mast cells: activation by hydroperoxides. AB - In order to identify regulatory steps in leukotriene synthesis, the biochemical characteristics of a 5-lipoxygenase activity in the 100,000 xg supernatant from sonicates of cells of an IL-3 dependent murine mast cell clone, MC-9 were determined. Principal products from exogenous 14C-arachidonic acid were identified as leukotriene B4, diastereomeric 5,12-dihydroxy-eicosatetraenoic acids (5,12 diHETEs) 5-hydroperoxy and hydroxyeicosatetraenoic acids (5-HPETE and 5-HETE) as well as a novel metabolite 5-oxo-6,8,11,14-eicosatetraenoic acid (5 oxo-ETE). The crude lipoxygenase activity had a pH optimum of 6.9 and was highly dependent upon added Ca++. The effective Ca++ concentration for 50 per cent activation (EC50) was 3 microM. Activity was also stimulated by ATP (EC50 = 160 microM). The cytosolic 5-lipoxygenase activity exhibited a biphasic concentration dependence for arachidonic acid with maximum product formation occurring at 35 microM (ca. 20 nmole/mg/4 min). The lipoxygenase activity exhibited apparent lag phase kinetics which were more pronounced at low protein concentrations (0.3 mg/ml). In addition, the lag phase was greatly accentuated by the addition of a hydroperoxide scavenging system consisting of glutathione (1 mM) plus glutathione peroxidase (0.4 unit/ml). In contrast, addition of any of several hydroperoxides, i.e. 5-,8-,9- or 15-HPETE (EC50 ca. 1 microM), but not the corresponding alcohols (5-HETE and 15-HETE), shortened the lag phase. These results show that the 5 lipoxygenase requires hydroperoxide for activation and that cellular level of hydroperoxides may be an important factor regulating leukotriene synthesis. PMID- 3099337 TI - [New possibilities of detecting Neisseria gonorrhoeae using the GONOZYME test]. PMID- 3099338 TI - Nursing workforce planning: it can be done, but is it? PMID- 3099339 TI - Aspirin and Reye's syndrome. PMID- 3099340 TI - Wage injustice: the past or present. PMID- 3099342 TI - The use of computed radiography for the determination of the impurities in 68Ga EDTA by paper chromatography. PMID- 3099341 TI - High-activity intraluminal 192iridium endocurietherapy for treatment of esophageal cancer. AB - Intraluminal endocurietherapy (ECT) with high-activity 192Iridium administered via catheter following megavoltage external-beam radiotherapy, allows delivery of 8,000-10,000 rad to the target volume without exceeding the normal tissue radiation tolerances of surrounding vital structures. The endocurietherapy does not require surgery, general or local anesthesia. The technique is accurate, cost effective, and allows safe delivery of higher radiation doses than could be tolerated by multiple-field external-beam megavoltage radiotherapy techniques alone. In a pilot Phase-1 toxicity study of six patients treated with minimum tumor doses of 8,000 rad, the majority of patients developed benign esophageal stricture 2-6 months following ECT which was managed by dilatation or gastrostomy. No patients developed esophageal perforation. Local tumor control was excellent, but a high proportion of patients developed distant metastatic disease. PMID- 3099343 TI - [The use of indomethacin in the prevention of peri-articular ossification in the surgical treatment of congenital hip dislocation in children]. AB - The authors have used indomethacin (30 mg per day for 4 weeks) in the post operative treatment of children who have had a surgical procedure for congenital dislocation of the hip--either an isolated Colonna procedure or associated with femoral shortening. It was concluded that indomethacin is effective in preventing or diminishing the incidence of post-operative para-articular bone formation. No secondary defects were noted. PMID- 3099345 TI - [Production of prostacyclin and endothelium-derived relaxing factor from endothelial cells]. PMID- 3099344 TI - [IgM myeloma. Report of 2 cases]. PMID- 3099347 TI - [Echocardiographic diagnosis of infectious endocarditis complicating parenteral feeding]. PMID- 3099346 TI - [A 67-year-old male with systemic disease, skin disease and polyadenopathies]. PMID- 3099348 TI - [Proteolytic susceptibility of alpha-amylase of the pancreas of swine deprived of its structural calcium]. AB - Hog pancreas alpha-amylase (alpha-1-4-glucan-glucan hydrolase, E.C. 3.2.1.1) lost its structural calcium by action of EDTA at 20 degrees C. Enzymatic activity experimented a decrease whereas a big increase in proteolytic susceptibility to bovine pancreas trypsin (E.C. 3.4.4.4) was shown. Native alpha-amylase had an activity of 2,730 mg maltose/min X mg enzyme and a Km of 0.222% amylose, the activity of calcium depleted amylase being of 1,640 mg maltose/min X mg enzyme and Km 0.571% amylose. Simple methods for evaluating proteolytic susceptibility of alpha-amylase micro-amounts against trypsin action, and for the measurement of alpha-amylase activity in polyacrylamide rod gels were also described. PMID- 3099349 TI - The mutagenicity of aflatoxin Q1 to Salmonella typhimurium TA 100 with or without rat or human liver microsomal preparations. AB - An investigation of the mutagenicity of aflatoxin Q1 in the Salmonella mutagenicity test is reported. This mammalian metabolite of aflatoxin B1 was marginally mutagenic to strain TA 98 when either rat or human liver microsomes were present in the test. However, it was mutagenic to TA 100 with the same liver activation sources in the assay. Moreover, it was mutagenic to TA 100 in the absence of liver microsomes. This Q1 mutagenesis, presumably a direct acting base substitution effect, was nearly equal to the liver activated mutagenesis. It was also greater in this respect than aflatoxin B1 or aflatoxicol. PMID- 3099350 TI - Humoral immune response to acetaldehyde adducts in alcoholic patients. AB - Sera of alcoholic patients were found to contain antibodies to acetaldehyde adducts as determined by immunodiffusion. Differences in antibody levels were determined by hemagglutination with acetaldehyde adduct-conjugated red blood cells. Anti-acetaldehyde adduct immunoglobulin titers in 21 healthy, non-drinking individuals ranged from 10-80, whereas 25 of 34 alcoholics had titers of 160 or above (P less than 0.001). Rabbit-polyclonal and mouse-monoclonal antibodies against acetaldehyde adducts did not agglutinate red blood cells of alcoholic patients, indicating that no detectable acetaldehyde-altered epitopes are present on erythrocyte membranes. These results suggest that acetaldehyde-induced immunogenic determinants can initiate a humoral immune response which may differentiate alcoholics from non-alcoholics. PMID- 3099351 TI - Regulation of in vitro human leukocyte interferon production: effect of prostaglandin synthetase and phosphodiesterase inhibition. AB - A great variability exists in the in vitro capability of peripheral blood leukocytes (PBL) of apparently healthy adults to produce IFN-alpha. In this report, we have studied the effects of prostaglandins, indomethacin and pentoxifylline upon IFN-alpha production by the PBL of normal healthy donors. The donors were divided into two groups: "normal producers" - donors that consistently produced greater than 2,000 ref. units IFN-alpha per 10(7) PBL and "low producers" - donors that consistently produced less than 2,000 ref. units IFN-alpha per 10(7) PBL. Addition of exogenous PGE1 or PGE2 into interferon production media significantly inhibited IFN-alpha yield by the PBL of both normal and low producers. The inhibition was dose dependent. A significant rise in the IFN-alpha yield was seen when PBL of "low producers" were exposed individually to either pentoxifylline or indomethacin. However, no increase in titer of IFN-alpha was seen when PBL of "normal producers" were exposed to either of these two agents during interferon production periods. With regard to PBL of "low producers", the enhancement of IFN-alpha yield was further potentiated when both indomethacin and pentoxifylline were utilized concurrently at their optimal concentrations. These results suggest that enhancement of IFN-alpha production by PBL of apparently healthy adults who are low producers may be possible and may have preventive value. PMID- 3099352 TI - Comparative study of conventional scalpel and CO2-laser in experimental tumor surgery. AB - The study hereby submitted has been designed to show whether there are any differences between using a conventional knife or a CO2-laser when excising and grafting tumors in animal experiments. The animals were C57B1/6 mice, the tumor was the Lewis lung carcinoma. Eight days after tumor inoculation into the s.c. layer of the back, 213 mice were treated by tumor excision either with a conventional knife or a CO2-laser. Eighty-six excised tumors were cut, and the tumor surface was swabbed into the s.c. layer on the nape of 86 tumor-free mice. Survival times of the laser-operated animals were insignificantly longer. However, small tumors showed markedly longer survival times. The interval without recurrence was longer for all tumor sizes when the laser was used (P less than 0.005). The laser method yielded lower growth rates when the tumor surface was swabbed into tumor-free mice (P less than 0.0001). Histological and cytologic tests of the laser-excised and- swabbed specimen demonstrated a high rate of cell destruction. Therefore, the CO2-laser seems to have some significance in cases where the incision is made close to the tumor or where tumor surfaces may be lesioned. PMID- 3099353 TI - Clinicopathologic features in two cases of multiple myeloma. AB - Multiple myeloma is a serious and fatal condition with various ocular manifestations. In two of these cases, pathologic findings included opaque ciliary body cysts, a ciliochoroidal effusion, retinal microaneurysms and hemorrhages, and detachment of both the sensory retina and the retinal pigment epithelium. In one case, a recanalized thrombus within a retrolaminar vein and direct continuity of a superonasal retinal detachment with a large pars plana cyst was observed. The proteinaceous material in the anterior chamber, ciliary body cysts, choroid and ciliary body, subretinal, and subretinal pigment epithelial areas was identified as immunoprotein using an immunoperoxidase technique. PMID- 3099354 TI - [Effect of nitroglycerin on coronary artery dilatation and hemodynamics: comparison among sublingual, intravenous, and intra-coronary administration]. PMID- 3099355 TI - [2 cases of nodoventricular Mahaim fiber]. PMID- 3099356 TI - Effects of PCO2, pH and extracellular calcium on contraction of airway smooth muscle from rats. AB - The effect of changes in PCO2 on airway smooth muscle was studied in acetylcholine-induced contractions of isolated rat trachea. Elevation of superfusate PCO2 from control PCO2, 38 mm Hg (pH 7.49), to 168 mm Hg (pH 6.74) decreased tension to 68% of control tension; reduction of PCO2 to 19 mm Hg (pH 7.84) increased tension to 104%. Similar effects on tension occurred when pH was altered by varying superfusate bicarbonate concentration at constant PCO2. Modification of the response to changes in PCO2 by varying extracellular calcium (Ca2+) concentration and also by verapamil indicated that changes in PCO2 and pH may alter Ca2+ uptake by the smooth muscle. Calcium uptake was measured by 45Ca2+ and the lanthanum method. At control pH 7.49, net Ca2+ uptake was 5.34 mmol Ca2+/kg trachea 60 min after the onset of contraction; this decreased to 4.26 at pH 6.88, and increased to 6.58 at pH 7.85. The results suggest that the mechanism whereby changes in PCO2 affect airway smooth muscle contraction is a pH-dependent alteration of Ca2+ uptake. PMID- 3099357 TI - [Inhibitory effect of sodium thiomalate on the extracellular release of lysosomal enzymes in rats with adjuvant arthritis]. PMID- 3099358 TI - [Inhibitors of factor VIII in non-hemophilic patients. Biological and therapeutic aspects. Apropos of 3 cases]. AB - A coagulation inhibitor of the anti-factor VIII: C type was detected in three non haemophilic male patients aged 75, 70 and 52 respectively. In all three patients antibody titres were low (less than 12.5 Bethesda units initially, less than 20 units subsequently), and a low but detectable level of factor VIII: C persisted (7 to 12 p. 100 in two patients who had severe haemorrhages and 2.100 in the third one). The 3 inhibitors inactivated factor VIII: C with a complex, type II kinetics (Biggs et al.). Strong doses of anti-haemophilic A fractions were biologically effective in one patient but could not stop severe bleeding. Activated plasma fractions were used successfully on several occasions. Once, moderate and repeated doses of anti-haemophilic A fractions resulted in satisfactory correction of factor VIII: C level, and a minor surgical operation could be performed. An immunosuppressive treatment was administered for 3 weeks to one patient and for 3 months to the other two patients. In all three cases the inhibitor disappeared after 5 to 8 months. In non-haemophilic patients with factor VII: C inhibitor the treatment of haemorrhagic episodes must take into account the severity of bleeding, then the usually complex kinetics of the inhibitor; thus it cannot be a direct copy of the treatment used in haemophiliacs with type I inhibitors. PMID- 3099359 TI - [Structural and histochemical changes in the neuron-astrocyte complex in human and experimental focal epilepsy]. PMID- 3099360 TI - [A case from practice (68)]. PMID- 3099361 TI - [Peripheral and spinal mechanisms of nociception]. AB - Due to the combination of multidisciplinary studies, the last fifteen years have seen a major step forward in our knowledge of nociception. At the peripheral level the role of A delta and C polymodal cutaneous nociceptors is relatively well demonstrated in animal as well as in man. The activation of these nociceptors probably results from both direct effects of the stimulus and indirect effects, mediated by the release of various chemicals. The specific roles of articular, muscular and visceral fine afferent fibers in nociception, is less well understood. Cutaneous A delta and/or C fibers terminate mainly in the superficial zones (laminae I and II outer) of the dorsal horn. The nature of the transmitter (s) released by nociceptive afferents is still unknown. Substance P has long been a candidate but the multiplicity of peptides revealed by immunohistochemical techniques and their coexistence on occasions in the same dorsal root ganglion cells question a unequivocal role of substance P. At the level of the dorsal horn of the spinal cord, nociceptive specific and nociceptive non-specific units have been described in laminae I, II, IV to VI. It is generally held that nociceptive specific neurons are mainly found in the superficial laminae which also contains nociceptive non specific cells. Convergence of cutaneous, muscular and visceral inputs on these neurons is indicative of a role of both cell types in referred pain where consideration must also be given to the possibility of dichotomizing afferent fibers serving cutaneous and visceral territories. The involvement of contralateral ascending pathways (spinothalamic and spinoreticular tracts) in the transmission of nociceptive messages toward supraspinal structures is well established while the role of ipsilateral ascending systems (spino-cervical and dorsal columns post synaptic fibers) is still questioned. Both segmental and descending modulating controls are exerted at the spinal level. At segmental levels, the inhibitory action of large diameter cutaneous fibers is now well established. The action of fine fibers seems also to be inhibitory. Descending influences are exerted from the periaqueductal gray matter and the ventromedial medulla (mainly the nucleus raphe magnus). They are sustained by serotoninergic and noradrenergic mechanisms and they involve to a lesser extent the endogenous opioids. The physiological function of these descending systems is still sharply discussed. PMID- 3099362 TI - Bone and joint infections in intravenous drug abusers. AB - An analysis of data on 45 intravenous drug abusers treated for skeletal infection in 1982-1983 is presented. Eighty percent of patients were younger than 40 years old. None had any serious underlying illnesses. Septic arthritis was noted in 33 patients, osteomyelitis in seven, and both in five. Bone or joint infection involved the extremities in 78% of patients. The knee joint (left, 11 patients; right, four) was most commonly affected, and the left groin was the most frequent site of drug injections, a finding that suggests a relationship between the sites of injection and infection. Fever was absent in 16 (36%) of 45 patients. The predominant pathogens isolated were methicillin-resistant Staphylococcus aureus and groups A and G streptococci. Pseudomonas aeruginosa was much less common (11% of patients). Treatment included bed rest, intravenous antibiotics, and arthrocentesis when needed. Surgery was required in only seven (16%) of 45 patients. The immediate prognosis for intravenous drug abusers with skeletal infection was excellent. Attempts to obtain follow-up information from most patients, however, were unsuccessful. PMID- 3099363 TI - Endogenous aspergillus endophthalmitis. AB - A 27-year-old man with a history of intravenous-narcotic abuse presented with signs and symptoms suggesting fungal endophthalmitis. He underwent core vitrectomy with intravitreal injection of amphotericin B. Aspergillus flavus grew from cultures of the vitreous aspirate. There was no evidence of extraocular infection, and the patient was treated postoperatively with subconjunctival amphotericin B and oral flucytosine. Unlike previously reported cases of endogenous aspergillus endophthalmitis in drug abusers, the patient described here recovered normal visual acuity. PMID- 3099364 TI - Brain abscess due to Listeria monocytogenes: case report and literature review. AB - Listeria monocytogenes is an uncommon cause of brain abscess. Of a total of 14 cases of L. monocytogenes brain abscess (one described for the first time and 13 reported previously in the English-language literature), seven (50%) occurred in patients with leukemia and recipients of renal transplants; four (29%) of the cases occurred in previously healthy individuals. Common clinical findings were similar to those in brain abscess due to other causes and included fever (57%), headache (57%), and focal neurologic signs (64%). Distinctive, however, was the unusually high frequency of associated meningitis and bacteremia; blood cultures were positive in all eight cases in which they were performed. Eight (57%) of the 14 patients died. L. monocytogenes should be included in the differential diagnosis of brain abscess in patients with leukemia and in renal transplant recipients. Listerial brain abscess is highly unlikely when blood culture results are negative. PMID- 3099365 TI - [Intestinal activity of disaccharidases in schistosomiasis mansoni. Study of the course in mice with various degrees of infestation]. PMID- 3099366 TI - Antigen characterization of vector-borne and cultured metacyclic trypomastigotes of Trypanosoma cruzi. PMID- 3099367 TI - Destruction of lymphocytes by a non-viral fraction of HTLV III positive patients' plasma. PMID- 3099368 TI - Are we ready for the challenge in long-term care. PMID- 3099370 TI - Why some patients suffer a zinc deficiency. PMID- 3099369 TI - If you're asked to pull out a feeding tube. PMID- 3099371 TI - Will i.v. feeding endanger your patient? PMID- 3099372 TI - [Fabry's disease. Rare etiology of a long-term inflammatory syndrome. Apropos of a case]. AB - A man aged 54 years presented multiple symptoms (acroparesthesia, familial deafness, cardiomyopathy, diarrhea, adenopathy with infiltration of frothy macrophages, pancytopenia with a dense marrow, chronic meningitis, renal failure) associated with intermittent fever, with feverish attacks and a temperature of 40 degrees C, and with a severe biologic febrile syndrome. Fabry's disease was diagnosed only after 3 years of fruitless explorations. The reasons for this delay are analysed and it is suggested than Fabry's disease be added to the list of conditions responsible for fever or for a persistent inflammatory syndrome. PMID- 3099373 TI - Nuclear thyroxine binding in human mononuclear blood cells. PMID- 3099374 TI - Comparative aspects of mammalian spermiogenesis. AB - The testes of some different orders of eutherian mammals were examined by conventional electron microscopy with respect to their pattern of spermiogenesis. In addition, some of the testes were studied by cytochemical methods for demonstration of certain nuclear proteins and of glycoproteins in the acrosome and the plasma membrane of spermatids. It was found that although the basic pattern of spermiogenesis was similar in all species studied, there were pronounced dissimilarities in the final shape of the spermatids. Differences were also observed in the timing of the differentiation of several organelles. The head of late spermatids and spermatozoa of Primates, Carnivora and Perissodactyla was cone-shaped, whereas in Artiodactyla and Lagomorpha it was flattened or paddle-shaped, and in Rodentia hook-shaped. The size and shape of the acrosome varied considerably between the orders, as did the length of the middle piece. PMID- 3099375 TI - Correlative scanning electron microscopy in the study of human gastric mucosa. AB - We studied two aspects of the human gastric mucosa: the surface morphology of mucous cells, as viewed by scanning electron microscopy (SEM); the glycosidic components of intracellular mucins, characterized by means of lectins. The latter were conjugated with fluorescein isothiocyanate and with colloidal gold-silver for the visualization of the reaction products in light microscopy (LM) and in SEM (backscattered mode) respectively. The surface morphology of mucous cells appears to be correlated to the secretory state. In gastric ulcers we found a prevalence of non-secreting cells. A decrease in glycosidic receptors for fucose binding lectin and galactose-(1-3)-N-acetyl-galactosamine-binding lectin was also observed. This suggests the presence of an impaired mucus secretion which may play a role in the pathogenesis of gastric ulcer. Spiral bacteria, supposed to be aetiologically related to peptic ulcer and gastritis, were easily detected by SEM. Intestinal metaplasia defined "complete" in LM showed surface morphology and glycosidic components different from those of true intestinal mucosa. This implies the necessity of taking into account also these parameters when classifying this lesion. The same applies to polyps. Our data indicate that correlative SEM may contribute further information on the pathogenesis and pathology of gastric diseases. PMID- 3099377 TI - Sequential scanning electron microscopic analyses of normal and spontaneously occurring abnormal ocular development in C57B1/6J mice. AB - Embryos of C57B1/6J mice were examined grossly, and by light and scanning electron microscopy on days 8 through 19 of gestation. Adult eyes were examined by slit lamp biomicroscopy and light microscopy. A spontaneous incidence of eye malformations including microphthalmia, microphakia, corneal opacity and anterior segment dysgenesis was observed at a rate of 13.2% in the adults and 10.8% in the day 14 embryos. Scanning electron microscopy demonstrates the complex series of coordinated changes in shape and tissue interrelationships observed in normal ocular development. Possible routes of abnormal ocular morphogenesis beginning as early as the time of optic vesicle formation are discussed. PMID- 3099376 TI - The morphologic categorization of cell death induced by mild hyperthermia and comparison with death induced by ionizing radiation and cytotoxic drugs. AB - This paper presents a summary of the morphological categorization of cell death, results of two in vivo studies on the cell death induced by mild hyperthermia in rat small intestine and mouse mastocytoma, and a comparison of the cell death induced by hyperthermia, radiation and cytotoxic drugs. Two distinct forms of cell death, apoptosis and necrosis, can be recognized on morphologic grounds. Apoptosis appears to be a process of active cellular self-destruction to which a biologically meaningful role can usually be attributed, whereas necrosis is a passive degenerative phenomenon that results from irreversible cellular injury. Light and transmission electron microscopic studies showed that lower body hyperthermia (43 degrees C for 30 min) induced only apoptosis of intestinal epithelial cells, and of lymphocytes, plasma cells, and eosinophils. In the mastocytoma, hyperthermia (43 degrees C for 15 min) produced widespread tumor necrosis and also enhanced apoptosis of tumor cells. Ionizing radiation and cytotoxic drugs are also known to induce apoptosis in a variety of tissues. It is attractive to speculate that DNA damage by each agent is the common event which triggers the same process of active cellular self-destruction that characteristically effects selective cell deletion in normal tissue homeostasis. PMID- 3099378 TI - A hypothesis for the selection of available repertoires: T-cell network early in the intrathymic differentiation. PMID- 3099379 TI - Polyclonal lymphocyte responses to murine Trypanosoma cruzi infection. I. Quantitation of both T- and B-cell responses. AB - Lymphoid activity was studied in spleen and lymph node cells from Trypanosoma cruzi-infected mice. Blast transformation in each lymphocyte class was assessed by dual parameter analysis for size and surface markers by both FACS and conventional immunofluorescence, while proliferative activity was measured by tritiated thymidine uptake, autoradiography, and analysis of DNA content in single cells. Acute infection results in rapid blast transformation and proliferative activity of all three lymphocyte classes (Ig+, L3T4+, and Lyt 2+). At 2 weeks of infection most cells in these organs are enlarged and more than half are dividing. By 2 and 6 months after infection (chronic phase of resistant strains), large numbers of activated B lymphocytes and, to a lesser extent, of Lyt 2+ T cells are still detected. Similar results were obtained in C57BL/6 (resistant) and C3H/HeJ (susceptible) mouse strains. The implications of this massive polyclonal lymphocyte response to the parasite for the physiopathology of acute and chronic infection are discussed. PMID- 3099381 TI - The role of calcium in stimulation of activated T lymphocytes with interleukin 2. AB - In a study of the role of Ca++ in the stimulation of activated T lymphocytes with interleukin 2 (IL-2) it was found that IL-2-induced proliferation can occur independently of extracellular calcium. Further, there was no correlation between triggering of DNA synthesis and an increase in free cytoplasmic calcium. However, IL-2 induced an increased uptake of 45Ca++ from the extracellular medium. Since there is no increase in free cytoplasmic calcium, it must be assumed that this is caused by an increase in membrane-associated calcium. Further, the calcium channel-blocking agent, verapamil, and TMB-8, a putative inhibitor of mobilization of calcium from intracellular pools, both exerted a dose-dependent inhibition of IL-2-induced DNA synthesis in activated T lymphocytes. We conclude that calcium is not a second messenger in activated T lymphocytes stimulated by IL-2, but our results indicate that calcium may play a role at membrane level. PMID- 3099380 TI - Polyclonal lymphocyte responses to murine Trypanosoma cruzi infection. II. Cytotoxic T lymphocytes. AB - Intraperitoneal infection of young adult C57BL/6 males with 10(5) blood or cloned culture forms of Trypanosoma cruzi (CL strain) induced the appearance in spleen, blood, and lymph nodes of cytotoxic effector cells detectable in a lectin dependent 51Cr-release assay. The effector cells were conventional cytotoxic T lymphocytes (CTL), since they were Thy 1+ and Lyt 2+, and the lysis of tumour target cells was strictly dependent on the presence of lectin. CTL activity is already detectable in spleen 2 days after infection, reaches a peak at 2 weeks, and returns to normal levels during the chronic phase (1 month onwards). Increased levels of CTL activity were also detected in lymph nodes with similar kinetics, even in animals that were splenectomized prior to infection. In contrast to spleen, significant levels of CTL activity persisted in lymph nodes in the chronic phases. This functional variable correlates with the appearance of high numbers of large Lyt 2+ lymphocytes in the same organs (50 to 100-fold higher than in control, uninfected mice). Very similar responses are detected in a T. cruzi sensitive mouse strain (C3H/HeJ). It appears, therefore, that T. cruzi infection results in a large polyclonal activation of Lyt 2+ lymphocytes, some of which differentiate to effector, cytolytic functions. PMID- 3099382 TI - Inhibition of renal prostaglandin synthesis in man: methodological and clinical implications. AB - Integrity of renal prostaglandin synthesis is necessary to maintain renal cortical and medullary function in patients with kidney, heart and liver disease. A comparison of the biochemical effects of various non-steroidal anti inflammatory drugs (NSAIDs) necessitates that renal prostaglandin synthesis, as reflected by urinary immunoreactive prostaglandin excretion, be assessed with proper attention to problems created by seminal fluid contamination, inadequate chromatographic separation of samples, and largely unknown cross reactivities of systemic eicosanoid metabolites with antibodies raised against primary prostaglandins. Most, but not all, clinical studies support the observation that conventional doses of sulindac, administered orally, do not inhibit renal prostaglandin synthesis or alter renal function. Caution is in order, however, about the use of any NSAID, including sulindac at conventional dosage, in patients with severe liver disease as the plasma levels of sulindac sulfide are increased and prolonged compared to patients with normal hepatic function. Furosemide-induced natriuresis is probably not prostaglandin-mediated, in contrast to increased in renal blood flow and renin release. Some NSAIDs can attenuate the efficacy of antihypertensive therapy. Inasmuch as sulindac does inhibit systemic vascular prostacyclin production, its lack of hypertensive effect vis-a-vis other NSAIDs argues in favor of the importance of intrarenal prostaglandin-dependent mechanisms in mediating the hemodynamic effects of non selective cyclooxygenase inhibitors. PMID- 3099384 TI - [Mechanisms of exercise hyperpnea]. PMID- 3099383 TI - [Pulsatile long-term gonadotropin-releasing hormone (GnRH) therapy in the male: natural induction of puberty in a 20-year-old boy]. AB - Successful induction of puberty by means of a pulsatile long-term therapy with GnRH--the variant closest to nature--can be performed on an outpatient basis without changing habits and lifestyle, as was demonstrated clinically and biochemically in a 20-year-old previously untreated boy with hypothalamic hypogonadism of unknown etiology. Unusual in this patient's course was the slow- and modest--increase in plasma FSH levels. Evidence that puberty did not occur spontaneously but was in fact due to treatment was gained from gonadotropin profiling by night and day before and after therapy withdrawal. PMID- 3099385 TI - [Neurogenetics of the ACh system in Drosophila melanogaster]. PMID- 3099386 TI - Diabetic ketoalkalosis: a complex mixed acid-base disorder. AB - A mixed acid-base disturbance in a long-standing insulin dependent diabetic resulting in a combination of hyperglycaemic ketosis with an alkalosis is reported, in which an analysis of the biochemical mechanisms involved helped to clarify the clinical problem. PMID- 3099387 TI - Cloned gene of Rickettsia rickettsii surface antigen: candidate vaccine for Rocky Mountain spotted fever. AB - Two major protective antigens of Rickettsia rickettsii have been previously described. In this study, we cloned the gene encoding one of these antigens into Escherichia coli and tested the effectiveness of the recombinant-made product as a vaccine for Rocky Mountain spotted fever. A clone bank of R strain R. rickettsii DNA was made in E. coli K-12 by using the plasmid vector pBR322. Transformants were screened for their ability to make rickettsial antigens by reactivity with rabbit antibodies to R. rickettsii. One of the transformants, EM24(pGAM21), made a product reactive with two monoclonal antibodies that recognize a 155-kilodalton protein of R. rickettsii. One of the monoclonal antibodies was a member of a class of antibodies that react to heat-sensitive epitopes and protect mice injected with a potentially lethal dose of viable R. rickettsii. The cloned product contained this protective heat-sensitive epitope. In order to obtain enhanced expression, the gene was subcloned downstream of the lactose promoter on the plasmid vector pUC8. A sonic lysate of E. coli harboring the pUC8 subclone was used successfully as a vaccine to protect mice injected with a lethal dose of the viable R. rickettsii. PMID- 3099388 TI - In vivo activation of CD4+ cells in AIDS. PMID- 3099389 TI - Atomic structure of thymidylate synthase: target for rational drug design. AB - The atomic structure of thymidylate synthase from Lactobacillus casei was determined at 3 angstrom resolution. The native enzyme is a dimer of identical subunits. The dimer interface is formed by an unusual association between five stranded beta sheets present in each monomer. Comparison of known sequences with the Lactobacillus casei structure suggests that they all have a common core structure around which loops are inserted or deleted in different sequences. Residues from both subunits contribute to each active site. Two arginine side chains can contribute to binding phosphate on the substrate. The side chains of several conserved amino acids can account for other determinants of substrate binding. PMID- 3099390 TI - In situ detection of beta-galactosidase in lenses of transgenic mice with a gamma crystallin/lacZ gene. AB - Transgenic mice carrying the gamma 2-crystallin promoter fused to the coding region of the bacterial lacZ gene were generated. The offspring of three founder mice expressed high levels of the enzyme solely in the central nuclear fiber cells of the lens as measured by an in situ assay for the detection of beta galactosidase activity. These results suggest that gamma 2-crystallin sequences between -759 to +45 contain essential information required for appropriate tissue specific and temporal regulation of the mouse gamma 2-crystallin gene. In a broader context, this study also demonstrates the utility of beta-galactosidase hybrid gene constructs for monitoring the activity of gene regulatory elements in transgenic mice. PMID- 3099392 TI - Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET. AB - The regional distributions of monoamine oxidase (MAO) types A and B have been identified in human brain in vivo with intravenously injected 11C-labeled suicide enzyme inactivators, clorgyline and L-deprenyl, and positron emission tomography. The rapid brain uptake and retention of radioactivity for both 11C tracers indicated irreversible trapping. The anatomical distribution of 11C paralleled the distribution of MAO A and MAO B in human brain in autopsy material. The corpus striatum, thalamus, and brainstem contained high MAO activity. The magnitudes of uptake of both [11C]clorgyline and L-[11C]deprenyl were markedly reduced in one subject treated with the antidepressant MAO inhibitor phenelzine. A comparison of the brain uptake and retention of the 11C-labeled inactive (D-) and active (L-) enantiomers of deprenyl showed rapid clearance of the inactive enantiomer and retention of the active enantiomer within MAO B-rich brain structures, in agreement with the known stereoselectivity of MAO B for L deprenyl. Prior treatment with unlabeled L-deprenyl prevented retention of L [11C]deprenyl. Thus, suicide enzyme inactivators labeled with positron emitters can be used to quantitate the distribution and kinetic characteristics of MAO in human brain structures. PMID- 3099391 TI - The cytoskeletal protein vinculin contains transformation-sensitive, covalently bound lipid. AB - Vinculin, which is associated with the cytoskeleton of many cells, has been suggested as a possible linker between microfilament bundles and the plasma membrane. Here it will be shown that fatty acid is covalently attached to vinculin in vivo. Furthermore, in chicken embryo fibroblasts infected with a temperature-sensitive mutant of Rous sarcoma virus, tsNY68, the acylation of vinculin at the permissive temperature was less than one-third that at the nonpermissive temperature. Thus, the covalent binding of lipid to vinculin is a transformation-sensitive event. The covalent modification of vinculin by lipids could be directly or indirectly involved in its reversible association with membranes. This modification may also provide a mechanism to alter the organization of vinculin within cells and thereby play a regulatory role in anchoring or stabilizing microfilament bundles at plasma membranes. PMID- 3099393 TI - High-dose megestrol acetate therapy of ovarian carcinoma: a phase II study by the Northern California Oncology Group. AB - The activity of high-dose megestrol acetate was studied in 47 patients with epithelial ovarian cancers after failure of initial chemotherapy. The dose of megestrol acetate was 800 mg/d orally (PO) for 4 weeks and then 400 mg/d until tumor progression. Patients generally had far-advanced disease. Prior therapy included cisplatin, doxorubicin, and cyclophosphamide (PAC) or other cisplatin containing regimens in 37, other combinations in eight, and single agents in only two patients. Seventeen patients (36%) developed intestinal obstructions within the first 2 months on study. Tumor histology was serous in 37, endometrioid in six, and clear-cell in two. Two thirds of the tumors were histologic grade 3, and the others were grade 2. Complete remission was obtained in one patient, with time to progression of 4 months. There were three partial remissions, with times to progression of 4, 5, and 18 months. The overall response rate (complete and partial) was 8%. Three additional patients had minor remissions (3, 5, and 8 months), and five had stable disease, for 3, 4, 5, 6, and 9 months. There was no correlation of response with grade, histologic type, or site of disease, but responding patients had a longer survival from diagnosis to protocol entry and from protocol failure to death than did nonresponding patients. The major side effect of megestrol acetate was increased appetite, which caused one patient to withdraw from the study, and resulted in a 10- to 20-kg weight gain in five patients. Plasma levels of megestrol acetate averaged 600 ng/mL in the first month of therapy and decreased to approximately 400 ng/mL at 8 and 12 weeks, after the drug dosage had been reduced. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were markedly lower during megestrol therapy compared with pretreatment values. Megestrol acetate at 1 microgram/mL in vitro inhibited soft agar colony formation from one of 17 specimens of ovarian carcinomas. We conclude that megestrol acetate in high doses has modest, but definite, palliative effects in some patients with advanced ovarian carcinoma in whom chemotherapy has failed. A controlled trial of megestrol plus combination chemotherapy as first-line treatment of advanced ovarian carcinoma should be considered. PMID- 3099394 TI - [CO2 and BP sensitive units in the ventral medulla of rabbits]. PMID- 3099396 TI - [Daonil and Hemi-Daonil]. PMID- 3099395 TI - Preventive dentistry in a health centre: effectiveness and cost. AB - The clinical and economic effects of a programme of preventive dentistry for children in an inner-city health centre are compared with those for traditional restorative care. Reductions in the rate of dental caries are estimated to be 70% for children aged 4-6 after 4 years in the programme (dmft) and 85% for children aged between 7 and 10 years after 4 years (DMFT). The cost-effectiveness analysis on which the economic appraisal is based identifies the issue of differences in the quality of output as critical to choices between the two treatment regimes. The preventive programme was primarily intended for pre-school children; for this younger group, assumptions about the quality of the preventive outcome would have to value it at between 0.8 and 1.2 times the quality of the restorative outcome in order to make up the difference in cost between the two regimes. For 7-10 year olds, the 4-year analysis showed the preventive programme to be more costly than restorative care largely because of low rates of incremental change at these ages. These rates were partly influenced by the design of the study and partly by the eruption status of the permanent dentition across this age-group. There is a need for further study of measures of dental outcome which combine aspects of both the quality and length of life of teeth. PMID- 3099397 TI - [Zarontin]. PMID- 3099398 TI - Cervical cancer. AB - This conference concerns economic, psychosocial, preventive, and medical aspects of the care of an indigent, unemployed, 22-year-old mother of three who died of an invasive, large cell, nonkeratinizing cervical cancer 35 months after her last Pap smear, 19 months after the onset of vaginal discharge, 12 months after consulting a physician, 10 months after an exploratory laparotomy, nine months after initiation of radiation therapy, five months after performance of a colostomy, four months after initiation of chemotherapy, and three months after treatment of small bowel obstruction with hyperalimentation and resection. We discuss the cost effectiveness of preventive programs. PMID- 3099399 TI - [Incidence of ABO and rhesus system antigens in patients with urolithiasis]. PMID- 3099400 TI - The conventional versus the new radiological contrast media. Cost-benefit analysis and medicolegal implications. AB - New iodinated radiological contrast media, which are safer but much more expensive than the conventional ones, have been introduced. Since the financial implications are considerable a compromise between cost and safety is inevitable. It is therefore recommended that, at present, the conventional media be used routinely and the new media be reserved for potentially painful examinations and for patients at higher risk. Should a question of wrongfulness or negligence concerning the use of contrast media be considered by our courts, they will undoubtedly be influenced by what is considered 'common practice' and 'accepted practice' within a medical specialty and that may be co-determined by socio economic considerations. PMID- 3099401 TI - [Perspectives in the clinical application of pancreas transplantation in the diabetic]. AB - Until June 1983 a total of 280 human pancreatic transplantations had been performed world-wide. Until July 1983, 57 were functioning (22%), 11% for more than 12 months. During the past 5 years a steady increase in the number of segmental transplants has been observed. In most cases simultaneous transplantation of pancreas and kidney was performed (144 cases), in 65 cases the pancreas was transplanted metachronously after kidney grafting, and in 64 cases pancreatic transplantation was performed alone. Currently, segmental or whole pancreatic transplantation is the favoured procedure. Islet transplantation has been disappointing because of the difficulty in procuring sufficient numbers of islets from an adult pancreas followed by immunological destruction of the transplanted islets. Most pancreas grafts have been procured from cadavers, but the favoured segmental technique allows living related donors to be used. After rejection the graft does not always have to be removed and exogenous insulin administration may be resumed, either permanently or until re-transplantation can be accomplished. Life-long immunosuppression is needed after transplantation and currently pancreatic allograft survival rates for cyclosporin (CSA) and azathioprine-treated patients have been similar. The longest survival of a living diabetic recipient with a functioning pancreas is 5 1/2 years. Some authors have recently claimed improvement and stabilization of impaired nerve conduction and diabetic retinopathy after pancreatic transplantation. PMID- 3099402 TI - Legislation affecting nursing practice. PMID- 3099403 TI - Hyperosmolar glucose prevents stress ulceration in the rat restraint model despite inhibition of endogenous prostaglandins. AB - Stress ulceration continues to be a problem in critically ill surgical patients and occasionally occurs even when prophylaxis is attempted with standard agents. Tube feedings protect against ulceration in clinical settings. Many tube feeding formulas and intragastric 25 per cent glucose alone prevent gastric lesions in the rat restraint model. Endogenous cytoprotective prostaglandin release is stimulated by the application of hyperosmolar sugar solutions to the gastric mucosa. To determine whether all or part of the protection afforded by 25 per cent glucose is mediated through stimulation of endogenous prostaglandins, hyperosmolar glucose was tested in restrained rats with and without concurrent cyclo-oxygenase blockade. Intragastric hyperosmolar glucose protected against gross and microscopic gastric lesions, raised the blood glucose level and elevated the gastric mucosal pH. Although cyclo-oxygenase blockade alone worsened the lesions produced by restraint, blocking cyclo-oxygenase in the rats given 25 per cent glucose did not lessen the protective effect of hyperosmolar sugar. We conclude that endogenous prostaglandins are useful in gastric mucosal defense but are not necessary for the protection afforded by 25 per cent glucose. It is likely that providing glucose directly to the stressed gastric mucosa enhances several aspects of gastric mucosal defense. PMID- 3099404 TI - Old anatomy books. PMID- 3099405 TI - Anatomical basis for a technique of ulnar nerve transposition. AB - There are five major anatomical locations where the ulnar nerve may be compressed near the elbow. Multiple sites of compression are often noted clinically; in other cases, the site of compression is difficult to identify. Clinical experience and results of a series of 20 anatomical dissections suggest that local decompression or subcutaneous transfer may be performed without necessarily exposing all five locations, posing a risk of incomplete decompression. Submuscular transfer of the ulnar nerve decompresses all five locations simultaneously and thus theoretically may be more reliable. The potentially superior results predicted by this anatomical investigation have been confirmed in a clinical case review. Submuscular transposition of the ulnar nerve is reliable and safe, not only in the primary treatment of ulnar neuropathy at the elbow but also in revision of previous operations. PMID- 3099406 TI - Anatomical bases of patellar tendon grafts used in anterior cruciate ligament reconstruction. AB - In 24 fresh specimens the blood-supply of the infrapatellar fat-pad was investigated by injection. In some of the specimens, Clancy's pedicled patellar tendon graft for anterior cruciate ligament reconstruction had been performed before injection. The fat-pad is supplied by vessels forming a plexus supplying the tendon. In the tendon grafts injected after Clancy's procedure, no vessels were found penetrating the patellar tendon at its patellar and tibial attachments. Filled vessels were found by histologic methods and the Spalteholz technique. PMID- 3099407 TI - Anatomical bases of the study of the constraints to which the cervical spine is subject in the sagittal plane. A study of the center of gravity of the head. AB - The authors have determined the position of the center of gravity of six isolated formolized heads by the suspension method, based on the work of the Bordeaux anthropologist, Beauvieux; in his opinion, the nasion-opisthion line (root of nose to posterior edge of the foramen magnum) characterizes the horizontality of the head, irrespective of species. The center of gravity is situated at the middle of the nasion-inion line (root of nose to external occipital protuberance), behind the sella turcica, above and slightly in front of the external auditory meatus. In profile, the axis of gravity falls on leaving the center of gravity and passes in front of the cervical spine, which remains in balance thanks to a fulcrum lever whose two arms are equal when the gaze is directed 30 degrees downwards in relation to the horizontal. This is the true reference position for the cervical spine in the sagittal plane. PMID- 3099408 TI - Comparison of the structure of human intervertebral discs in the cervical, thoracic and lumbar regions of the spine. AB - Posterior and anterior heights, cross-sectional area and shape were measured for all the intervertebral discs in four spines from elderly human cadavers. Disc height was a minimum at the T4-5 level; thoracic discs were less wedge-shaped than those in the cervical and lumbar regions. Cross-sectional area increased from the cranial to caudal extremity; at the L5-S1 level the nucleus pulposus occupied a high proportion of this area. Cervical discs tended to have an elliptical cross-sectional shape, thoracic discs were more circular and lumbar discs tended to have an elliptical cross-section which was flattened or re entrant posteriorly. This shape distribution was quantified by defining a shape index which had a maximum value of 1 for a circular cross-section. Orientations of the reinforcing fibres in the outer lamellae of the anterior annulus fibrosus were measured from 27 discs by X-ray diffraction. For these measurements, C3-4, T7-8 and L2-3 were chosen as representative of cervical, thoracic and lumbar discs. The fibre tilt, with respect to the axis of the spine, was significantly less in the cervical discs (at 65 degrees) than in the thoracic and lumbar discs (about 70 degrees). These findings are interpreted in relation to differing functional requirements and possible mechanisms of failure in the cervical, thoracic and lumbar regions of the spine in the light of current knowledge on the biomechanics of the intervertebral disc. PMID- 3099409 TI - An anatomical study of the palmar cutaneous branch of the median nerve. AB - We present an anatomical study of the palmar cutaneous branch of the median nerve emphasizing its frequency, origin, perforation point at the transverse carpal ligament, point of emergence in the palm, width, length, divisions and innervation territory. For this purpose, fifty cadaver hands were dissected under a stereomicroscope and/or magnifying glass. The origin of the palmar cutaneous branch (PCB) was on the average 4.56 cm proximal to conventionally named "zero point" on the most distal transverse volar wrist crease. Perforation of the aponeurosis occurred on average 0.79 cm from the mentioned point and its emergence in the palm at 0.76 cm. The nerve had an average length of 5.24 cm. PCB's divisions in the palm resulted in a medial branch in 42%, a lateral branch in 92% and an intermediate branch in 100% of the hands studied. In six specimens PCB presented a deep branch which was directed toward the thenar eminence or made communication with the superficial branch of the palmar digital nerve or still penetrated between the first or second metacarpal. In 4% of the cases there was a communicating branch between the superficial branch of the radial nerve and the PCB. These anatomical results should be considered in the evaluation of the best surgical techniques for decompression of the median nerve in the carpal tunnel. PMID- 3099410 TI - Preliminary note on biometric data relating to the human coraco-acromial arch. AB - A biometric study based on 20 human scapulae made it possible to specify the variations in the gap of the coraco-acromial arch in relation to its depth and height. A graphic representation in rectangular coordinates, then in spatial representation in relation to the three planes of reference, leads to the following findings: the bony variations in the arch occur essentially: at the coracoid apophysis, and two types of arch can be distinguished depending on the predominance of bony or of ligamentous components. PMID- 3099412 TI - Cholesterol lowering with total parenteral nutrition (TPN) PMID- 3099411 TI - An experimental study of traction on the cervical spinal nerves. AB - The authors present a study of experimental traction on 48 cervical spinal nerves obtained from fresh cadavers. 16 avulsions of the roots were produced, always after rupture of the dura mater. The different stages of traction and rupture are described, as well as the different specimens after rupture. Ways of protecting the spinal nerves against avulsion are discussed. PMID- 3099413 TI - [Patient classification is a guideline for personnel requirements. Interview by Karin Dorum and Soren Palsbo]. PMID- 3099414 TI - [Correlation coefficients of the basic indicators of cardiohemodynamics, blood gas levels and acid-base status in influenza]. AB - The main parameters of the cardiohemodynamics, blood gas composition and acid base balance were studied in 82 patients with uncomplicated influenza and in 124 patients with influenza aggravated by acute pneumonia. The disorders revealed were essentially dependent on the disease gravity and complications. To evaluate quantitatively the relationship between the respiratory and cardiovascular systems, use was made of the correlation ratios for all the pair parameters under study. The pulmonary artery pressure was highly dependent on the level of the diastolic systemic pressure in grave uncomplicated influenza (r = -0.932) and on the heart rate (r = +0.861) in influenza aggravated by pneumonia. These findings enabled the derivation of appropriate regression equations, which are simple and can thus be widely used in practice to measure the pressure in the pulmonary circulation and to correct pulmonary hypertension. The making up of the correlation schemes permitted evaluating the tendencies in the changes of the most important parameters of the cardiohemodynamics and homeostasis and forming a judgement about tension of the compensatory processes in the body during grave influenza and influenza complicated by acute pneumonia. PMID- 3099415 TI - [Food poisoning in patients with diabetes mellitus]. AB - The clinical picture of food toxoinfections in patients with diabetes mellitus is characterized by a more severe and protracted course. On the other hand, food toxoinfections promote diabetes mellitus decompensation and the development of diabetic ketoacidosis. Since diabetes mellitus and food toxoinfections have a number of symptoms in common the authors suggest the diagnostic working schedule. Grave and medium-grave food toxoinfections in patients with diabetes mellitus mandate refusing the intake of oral antidiabetic drugs and long-acting insulins. It is recommended that insulin may be administered in divided doses. PMID- 3099416 TI - [Ketoacidotic conditions in patients with diabetes mellitus (problems of classification and therapeutic tactics)]. AB - The paper is concerned with the characteristics of ketoacidotic conditions in patients with diabetes mellitus. The results of the clinical observation over 434 patients suffering from diabetes mellitus associated with diabetic ketoacidotic conditions of different gravity are analyzed. The causes that promoted the development of such complications and the clinico-biochemical characteristics of the patients are presented. Based on the analysis of the patients' condition, the laboratory and clinical findings the authors stress the necessity of differentiating between diabetic ketosis and ketoacidosis. The treatment measures are discussed in terms of the complications. It is indicated that in the treatment of ketoacidosis use can be made of splenin. The mechanisms of the beneficial effect of the drug on diabetic ketoacidosis are under discussion. It is also emphasized that diabetic ketoacidosis may develop in patients with any type and gravity of diabetes mellitus. Diabetic ketosis and ketoacidosis are regarded as different stages of the same disease. In case of the late and erroneous therapy any ketosis may transform to ketoacidosis. PMID- 3099417 TI - Teratogenesis of calcium valproate in rabbits. AB - The calcium salt of valproic acid (Valontin) has been proposed for use in the treatment of absence, myoclonic, and tonic clonic seizures of the primarily generalized type. The present study was conducted to determine the teratogenic potential of calcium valproate in rabbits. Groups of 20 Dutch-belted rabbits were given oral doses of 50, 150, or 350 mg/kg on days 6-18 of gestation. A reference group was given 350 mg/kg sodium valproate and control groups were untreated or given vehicle alone. Animals were observed daily and body weights were recorded on gestation days 0, 6, 13, 18, and 30. Litter and fetal parameters were evaluated following uterotomies on day 30. No drug-related clinical signs or deaths occurred. Postimplantation loss and the incidence of malformed vertebrae and ribs, rudimentary or absent pollices, and extra vertebrae and ribs were increased at 350 mg/kg with both calcium and sodium salts of valproic acid. At the 150-mg/kg dose level, calcium valproate markedly increased the incidence of supernumerary ribs. No teratogenic or embryotoxic effects were seen with calcium valproate at 50 mg/kg. These data indicate that the sodium and calcium salts of valproic acid exhibit teratogenic potential in rabbits. PMID- 3099418 TI - Risk, cost-effectiveness and profit: problems in cardiovascular research and practice. PMID- 3099419 TI - Inhibitory effects of three new synthetic compounds on human platelet aggregation. AB - Three compounds of the AQ series (benzothienyl-aminoethyl ketone derivatives), i.e. 3178 (benzothienyl-2 N,N-diallyl amino ethyl cetone), 1994 (alpha benzothienyl-beta-N-morpholino ethyl cetone), and 1989 (benzothienyl-2-beta-N,N dimethyl amino ethyl cetone) were tested against aggregations triggered by adenosine 5'-diphosphate (ADP), arachidonic acid (AA), paf-acether, thrombin or collagen under different experimental conditions. None of them exhibited a specific inhibitory effect on washed platelets prepared so as to render them specifically sensitive either to ADP, AA or paf-acether. Thus for compound 3178 AQ, the most potent of the three, IC50 values were 2.9 +/- 0.6, 2.9 +/- 1.0 and 4.3 +/- 0.9 uM (means +/- 1 SD of 4 experiments) against ADP, AA or paf-acether respectively. Aggregations triggered by subthreshold concentrations of thrombin were also inhibited by compound 3178 AQ (50 uM) even after washing, showing the persistence of the inhibitory effect. Inhibition was surmountable since addition of a 10 fold greater concentration of thrombin than the subthreshold one induced a full aggregation. When tested on platelet-rich plasma (PRP) higher concentrations of the inhibitors than those used on washed platelets were needed in order to counteract ADP, AA or paf-acether effects. Collagen-induced aggregation was also inhibited by the AQ compounds when tested either in PRP or in whole blood although, in the latter case, high concentrations of the antagonists had to be used. These data show that compounds of the AQ series bear a wide spectrum of activity which makes them potential anti-thrombotic agents. PMID- 3099420 TI - Inhibition of platelet aggregation by novel triphenylethylene analogs. AB - The present study has evaluated the effect of some newly synthesized triphenylethylene (TPE) analogs on platelet arachidonic acid metabolism and function. All compounds tested inhibited arachidonic acid induced platelet aggregation and several were superior to aspirin in their relative potency. Introduction of a carboxyl function into the alpha-ring, which should enhance binding according to proposed structural models for cyclooxygenase inhibitors, was not found to be beneficial. Increased structural rigidity, which resulted from covalent linkage of two aromatic rings in this series, did not eliminate anti-aggregatory properties. PMID- 3099421 TI - Release of both urokinase and tissue plasminogen activator from veins in vitro. AB - Specimens of human veins were incubated in culture media, in which the concentrations of urokinase (UK) and tissue plasminogen activator (t-PA) were determined by radioimmunoassay and immunoradiometric assay. Both UK and t-PA were released to the media, in which the concentration of plasminogen activators was correlated to the weight of the specimens. The release of t-PA was maximal on the first day, after which it rapidly decreased, and t-PA was not demonstrable after the third day of incubation. By contrast, UK was continuously liberated to the media during the study period of 5 days. The present results indicate that both UK and t-PA are present in the vein wall and probably released by different cells. PMID- 3099422 TI - Poly-lysines as modifiers of one- and two-chain tissue-type plasminogen activator activity. AB - Poly-L-lysine and certain mixed polymers of L-lysine and other amino acids modify the activity of one- and two-chain tissue-type plasminogen activator (t-PA) towards its substrates. In particular the rate of plasminogen activation in the presence of optimal poly-L-lysine concentrations, is increased by approximately 100-fold. In contrast, activity towards a small synthetic substrate is inhibited by 85%. These effects are observed with both the one- and two-chain forms of t PA. The use of poly-L-lysines in a coupled assay system optimised for t-PA and plasmin activities allows the reproducible assay of t-PA at the 10(-12) to 10( 13) molar level. PMID- 3099423 TI - The influence of glutathione and other thiols on human platelet aggregation. AB - The platelet membrane contains sulfhydryl groups which are essential for normal platelet function. Reduced glutathione (GSH) and other thiols such as cysteine and 6-mercaptopurine were found to inhibit human platelet aggregation induced by adenosine diphosphate (ADP), collagen and arachidonic acid. The inhibition of ADP induced aggregation by GSH (IC50 = 0.61 +/- 0.05 mM) was greater than that by cysteine (IC50 = 13 +/- 1 mM) or 6-mercaptopurine (IC50 = 5.4 +/- 0.2 mM). Two other thiols, dithiothreitol and beta-mercaptoethanol were found to cause platelet aggregation instead of inhibition. The interaction of GSH with the ADP receptor was noncompetitive in nature. PMID- 3099425 TI - Assay of factor VIII concentrates: comparison of the chromogenic and two-stage clotting assays. PMID- 3099424 TI - Effect of cobra venom phospholipase A2 on platelet aggregation in comparison with those produced by arachidonic acid and lysophophatidylcholine. AB - Cobra venom phospholipase A2 induced a biphasic effect on washed rabbit platelets. The first phase was a reversible aggregation which was dependent on stirring and extracellular calcium. The aggregation and thromboxane B2 formation were inhibited by indomethacin, mepacrine, tetracaine and imipramine, while PGE1 and sodium nitroprusside inhibited only the aggregation, but not the thromboxane B2 formation. The second phase was an inhibitory effect on platelet aggregation induced by arachidonic acid, PAF, ADP or collagen but not that by thrombin or ionophore A23187. The longer the incubation time of cobra venom phospholipase A2 with platelets, the more the inhibitory effect. The aggregating and anti aggregating effects could be overcome by bovine serum albumin. Lysophosphatidylcholine (Lyso-PC) and arachidonic acid showed synergistic inhibition in platelet aggregation. Lyso-PC decreased thromboxane B2 formation in platelets formed by collagen. The inhibitory effect of Lyso-PC on platelet aggregation was more marked at lower calcium concentrations. It is concluded that the aggregating effect of exogenous addition of venom phospholipase A2 is due to thromboxane formation and the antiplatelet effect is similar to those produced by arachidonic acid and lysophosphatidylcholine. PMID- 3099427 TI - Toxicity of calcium ionophore A23187 in monolayers of hypoxic hepatocytes. AB - Increased cytoplasmic calcium has been implicated in hepatic necrosis induced by cytochrome P-450-mediated halocarbon metabolism; hepatic necrosis is exacerbated hypoxia. It is known that addition of the calcium ionophore A23187 to a cell can mimic the metabolic causes of increased cytoplasmic calcium. In the present experiments, confluent monolayers of rat hepatocytes were exposed to A23187 (0.5 50 microM) under conditions of normoxia and 18-fold during a 4-h incubation at 0.5% (5 microM) O2 compared with 20% (212 microM) O2. The ED50 values of A23187 were 0.92, 1.84, 10.98, and 16.81 microM at 0.5, 1, 2, and 20% O2, respectively. The results demonstrate that small reductions in the oxygen concentrations normally encountered by pericentral hepatocytes (i.e., below 28 microM) may severely decrease the ability of these already compromised hepatocytes to manage perturbations in calcium homeostasis. PMID- 3099426 TI - Evidence for a free-radical-dependent metabolism of 7,12 dimethylbenz(a)anthracene in rat testis. AB - Polycyclic aromatic hydrocarbons, e.g., 7,12-dimethylbenz(a)anthracene (DMBA), cause various toxic effects in rat testis. To clarify the mechanism of action of DMBA in adult rat testis microsomes and mitochondria from this organ were investigated in vitro with respect to their capacity to metabolize DMBA. Qualitatively, both preparations showed DMBA-hydroxylase activities which were influenced by cytochrome P-450 inhibitors, chelators, and free-radical scavengers, suggesting that the DMBA metabolism was accounted for by different metabolic pathways in these organelles. Metabolism of DMBA was also accompanied by a pronounced covalent binding to both microsomal and mitochondrial protein, catalyzed primarily by a free-radical mechanism involving free or loosely bound iron which may involve superoxide anion shown to be generated by testis mitochondria. With microsomes covalent binding was markedly enhanced by added horseradish peroxidase but not by hydrogen peroxide whereas the mitochondrial binding was affected neither by added horseradish peroxidase nor by hydrogen peroxide. Antibodies raised against cytochrome P-450 c from rat liver inhibited the microsomal DMBA-hydroxylase but not the mitochondrial DMBA metabolism. It is concluded that the microsomal DMBA conversion and covalent binding are due to a mixture of cytochrome P-450 and free-radical-dependent metabolic pathways whereas the corresponding mitochondrial reaction is due mainly to a free-radical dependent pathway. However, the data do not allow for a conclusion as to the quantitative importance of these pathways. It is proposed that both pathways may be important in DMBA-dependent testis toxicity but also in polycyclic aromatic hydrocarbon-dependent testis toxicity in general. PMID- 3099429 TI - Mechanism of anestrus in rats treated with an antihypertensive agent, losulazine hydrochloride. AB - The mechanism of anestrus in rats treated with losulazine, a peripheral sympatholytic antihypertensive agent, was investigated by determining its effect on hypothalamic catecholamines and serum sex hormones and by evaluating the influence of bromocriptine on the reproductive functions of rats treated with losulazine. Groups of six female Upjohn Sprague-Dawley rats were treated orally with 10 mg/kg/day of losulazine and/or 18.75 mg/kg/day of bromocriptine for 15 or 27 days. Six rats were treated with losulazine plus 6.25 mg/kg/day of bromocriptine for 16 days followed by losulazine alone for 11 days. Rats treated with losulazine only were depleted of hypothalamic catecholamines, were hyperprolactinemic, and had interrupted estrous cycles and attenuated vaginal mucosa. Treatment with bromocriptine, a dopamine receptor agonist, resulted in suppression of serum prolactin and normal estrous cycles. Rats reverted back to hyperprolactinemia and anestrus shortly after bromocriptine withdrawal. These results suggest that hyperprolactinemia mediated through hypothalamic dopamine depletion is the mechanism of anestrus in rats treated with losulazine. PMID- 3099428 TI - Influence of serum cholesterol and albumin on partitioning of PCB congeners between human serum and adipose tissue. AB - The influence of serum lipids and proteins on partitioning of individual polychlorinated biphenyl (PCB) congener peaks between human serum and adipose tissue lipid was assessed using regression analysis. Subjects were 55 repair workers who were either currently or previously exposed, and 56 comparison workers without occupational exposure to PCBs. Seven congeners (2,4,5,4'-tetra CB, 2,3,5,2',3',6'-hexa CB, 2,3,4,2',3',6'-hexa CB, 2,3,4,2',4',5'-hexa CB, 3,4,5,3',4'-penta CB, 2,3,4,5,2',3',4'-hepta CB, and 2,3,4,5,2',3',4',5'-octa CB) which had been quantified in both serum and adipose tissue in at least one-third of the total study population were selected for evaluation. Initially the crude correlations between the serum PCB and certain candidate variables were assessed; more than one congener was correlated with serum cholesterol, albumin, triglycerides, low-density lipoproteins, very low-density lipoproteins, age, body fat content, and average servings of fish per day. Stepwise regression of log serum congener concentration on log adipose congener concentration and these variables was performed. Only cholesterol, albumin, and average servings of fish per day were significant for at least one congener peak. Congeners behaved in two groups, depending on their order of chromatographic elution. For 2,4,5,4'-tetra CB, 2,3,5,2',3',6'-hexa CB, and 2,3,4,2',3',6'-hexa CB, log serum concentration was not significantly correlated with log adipose congener concentration, and there was no consistent pattern for significant candidate variables. For congeners 2,3,4,2',4',5'-hexa CB, 3,4,5,3',4'-penta CB, 2,3,4,5,2',3',4'-hepta CB, and 2,3,4,5,2',3',4',5'-octa CB, log serum congener concentration was consistently significantly correlated with log adipose congener concentration and serum cholesterol positively, and with serum albumin negatively. For these four congeners the explanations of variation (R2) in serum congener concentration using adipose congener concentration alone were 3, 23, 20, and 30%, respectively, and after adding cholesterol and albumin were 13, 56, 43, and 46%. Thus we conclude that serum cholesterol and albumin can influence the distribution or partition of PCBs between serum and adipose tissue. PMID- 3099430 TI - The 3-methylcholanthrene-mimetic effect of 4,4'-dichlorobiphenyl-treatment on phenacetin-induced hepatic glutathione depletion and liver microsomal phenacetin O-deethylation in rats. AB - Both 4,4'-dichlorobiphenyl (4,4'-DCB) and 3-methylcholanthrene (3-MC) caused a substantial increase of phenacetin-induced hepatic glutathione (GSH) depletion, whereas phenobarbital (PB) had no effect, suggesting that 4,4'-DCB possesses cytochrome P-448 inducing activity. The O-deethylation of phenacetin by liver microsomes from control and PB- and 4,4'-DCB-treated rats showed biphasic Michaelis-Menten kinetics, in contrast to the monophasic course after pretreatment with 3-MC. Hepatic phenacetin levels indicated that in vivo interaction with only a high affinity site is involved in the O-deethylation of phenacetin. 4,4'-DCB and 3-MC caused marked increases in intrinsic clearance and extraction ratio of phenacetin, whereas control values were obtained after PB treatment. Because of an absence of a spectral change at low phenacetin concentrations, it could not be demonstrated whether the observed differences in metabolism should be ascribed to a change in binding of phenacetin to cytochrome P-450. The results of this study indicate that after pretreatment with various enzyme inducers the phenacetin-induced hepatic GSH depletion strongly correlates with microsomal phenacetin O-deethylation. Further, these findings suggest a discrepancy between 4,4'-DCB and PB in cytochrome P-450 inducing activity, as 4,4'-DCB mimics 3-MC in the induction of phenacetin O-deethylase. The difference between 4,4'-DCB and PB is discussed in relation to the multiplicity and induction of cytochrome P-450 isoenzymes. PMID- 3099431 TI - Mutagenic evaluation of tolbutamide and glybenclamide on the bone marrow cells of mice. AB - Mutagenicity of tolbutamide (TB) and glybenclamide (GL) was evaluated in vivo by the micronucleus test (MNT) in mice. Various doses of either TB or GL, as suspension in 1% gum-acacia, were orally administered to the animals, twice, at an interval of 24 h. 6 h after the second treatment, bone-marrow smears were prepared, stained and examined for the occurrence of micronucleated erythrocytes. Animals receiving the vehicle only, served as control. TB only at two higher dose levels induced significant increase in the percentage of micronucleated erythrocytes over that of the control, but GL failed to do so. PMID- 3099432 TI - [Inhibition of dental plaque by pepsin]. PMID- 3099433 TI - Ocular hypotony. AB - In hypotony, where the intraocular pressure is lower than the episcleral venous pressure, aqueous humour outflow must be via unconventional channels, such as uveoscleral outflow pathways. The level of intraocular pressure will be determined by the rate of aqueous humour production and the facility of unconventional outflow. The facility of unconventional outflow has been shown to be increased in eyes with experimentally-induced hypotony from cyclodialysis, ciliochoroidal detachment, iridocyclitis, or retinal detachment. Aqueous humour production is reduced in eyes with hypotony during the acute phase following cyclodialysis, and in eyes with iridocyclitis or rhegmatogenous retinal detachment. Chronic cyclodialysis or ciliochoroidal detachment does not lead to reduced aqueous humour production, if unassociated with iridocyclitis. Detachment of the ciliary body in hypotony is often associated with, but does not appear to cause, reduced aqueous humour formation. Apart from treatment of the specific cause of hypotony, reduction of the accompanying inflammatory response is essential for normalisation of aqueous dynamics and intraocular pressure. PMID- 3099434 TI - Partial protection of baboons against Schistosoma mansoni using radiation attenuated cryopreserved schistosomula. AB - Three groups of five baboons were vaccinated in Kenya using three doses of 10,000 viable cryopreserved schistosomula attenuated with either 10, 20 or 60 krad 60Co irradiation prepared in England. Animals were vaccinated at four-week intervals, challenged after a further six weeks with 2,000 cercariae and perfused at 10 weeks after challenge. High antibody titres to schistosomula mediating in vitro cytoadherence with P 388D1 macrophage-like cells were demonstrated in all vaccinated animals but not in controls. Significant titres to soluble egg antigen (SEA) were also demonstrated by ELISA in the 10 and 20 krad vaccinated groups following the first vaccination. The subsequent vaccinations and the challenge boosted this response considerably. Mean anti-SEA titres were only elevated above background in the 60-krad group six weeks after the third vaccination and in the challenge controls six weeks after challenge. Peripheral eosinophil counts were slightly reduced and neutrophil counts slightly elevated before challenge while eosinophil and erythrocyte counts were elevated and neutrophil counts depressed after challenge. PCV values were erratic in all groups. Eggs appeared in the faeces from six weeks after challenge and excretion rates were higher in all three vaccinated groups than in the challenge controls by necropsy 10 weeks after challenge. Body-weights were depressed in all groups after challenge but subsequently rose in the 10 and 20 krad groups. The 60 krad and challenge control groups lost 12.4% and 7.9% of body-weight respectively after challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099436 TI - An evaluation of the ELISA for schistosomiasis in a hospital population. AB - In order to evaluate the ELISA for schistosomiasis under the conditions of clinical practice, 1576 hospital patients were tested using a crude soluble Schistosoma mansoni egg antigen. Test sensitivity in detection of S. mansoni was found to be 96.2% and in S. haematobium 92.3%. The predictive value of positive results was high, reaching 88% at antibody levels three or more times the screening level. The test was considered by clinicians to be valuable for diagnosis and patient management, though it did not distinguish active from recently treated infections. Of 37 apparently false positive schistosome ELISA results only seven could be attributed to other helminth infections. Another nine patients had hepatitis. It is suggested that the antigens and antibodies of the two diseases are mutually cross-reactive, since reports have suggested a high increase of HBsAg patients with schistosomiasis. PMID- 3099435 TI - Ajmaline-induced electrocardiographic changes in chronic Trypanosoma cruzi infected rats. AB - In the present study, the ajmaline test was applied to T. cruzi-infected rats and evaluated for the ability to reveal ECG disturbances. The test consists of intravenous injection of ajmaline (2 mg/kg body-weight) under ether anaesthesia, and continuous ECG monitoring (right precordial lead: V1 or V2, 100 mm/sec paper speed). The animals used for the test (n = 30) had been experimentally infected with the Colombia strain of T. cruzi (1,000 parasites/g body-weight, newly weaned rats) one year before the experiments. Control non-infected rats (n = 21) were similarly maintained and treated. The ECGs were analysed under baseline conditions, i.e., before ajmaline, and 15, 30, 60 and 180 seconds after completion of ajmaline injection through the dorsal vein of the penis. The following parameters were studied: heart rate, PR interval, QRS and Qat duration. Morphological changes of the QRS complex and ST-T segment were also recorded. Under baseline conditions, the two groups had comparable values for all parameters, except for the PR interval, which was significantly increased in infected rats. No changes in wave rhythm or morphology were detected under baseline conditions. The PR and QaT intervals and QRS duration were significantly longer in both groups after ajmaline injection, at all periods studied. When the two groups were compared for relative variations, consistently and significantly higher alterations (p less than 0.05) were observed in the T. cruzi-infected group, except for the QaT interval at 180 seconds. However, the severe rhythm and ventricular conduction disturbances detected in 30% of the infected rats represented clear-cut discriminative alterations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099437 TI - Trypanosoma cruzi: zymodemes associated with acute and chronic Chagas' disease in central Brazil. AB - The clinical characteristics of acute and chronic Chagas' disease in central Brazil are described (29 acute cases and 111 chronic cases). The geographical distribution of Trypanosoma cruzi zymodemes in this region was mapped. Zymodeme (Z) 1 was identified in 12 acute cases, Z2 in 13 and repeated xenodiagnosis gave the same zymodeme identification. The clinical pictures of the Z1 and Z2 acute phases were similar. Resistance to benznidazole treatment occurred after either Z1 or Z2 acute infections. Only 14 positive xenodiagnosis were obtained from the 111 chronic phase patients examined. For 12 of these 14 patients the zymodeme was identified. All 12 carried Z2, 10 of whom had mega involvement. There were several possible explanations for the failure to detect T. cruzi Z1 in chronic Chagas' disease with mega syndromes: suggestions were made for follow-up investigations. PMID- 3099438 TI - Triatoma spinolai in Chile: a new host for Hepatozoon triatomae. PMID- 3099439 TI - Nytrel filters not re-usable. PMID- 3099440 TI - Immunohistologic analysis of human renal allograft dysfunction. AB - The value of percutaneous core needle biopsy in the immunohistological evaluation of renal allograft dysfunction was studied in 72 consecutive biopsies performed in 42 patients. The phenotypes of infiltrating cells mediating graft destruction were identified with monoclonal antibodies and immunoperoxidase staining techniques. Light microscopy, electron microscopy, and immunofluorescence staining were performed in all biopsies. Biopsies were divided into groups depending on their classification on the basis of standard histologic criteria, i.e., acute tubular necrosis (ATN), acute interstitial rejection, acute vascular rejection, chronic rejection and renal disease in native kidneys (RDNK) of nontransplant patients. Immunohistologic analysis of graft biopsies showed a significant increase in Leu 1 (pan-T cells), (P less than 0.001), Leu 2 (cytotoxic/suppressor cells) (P less than 0.001), and Leu 3 cells (P less than .05) in acute interstitial rejection. The expression of DR antigen was significantly increased in both acute (P less than .025) and chronic (P less than .05) rejection, when compared with the findings in ATN biopsies. Leu M1 (monocytes/activated T cells) and Leu 10 (B cells/macrophages) were significantly increased (P less than 0.05 and P less than .005, respectively) in acute interstitial rejection only. The helper/suppressor ratio of infiltrating cells showed no significant change in any clinopathologic category. There was no correlation between the cell populations infiltrating the graft and those monitored in the peripheral blood. Allograft mononuclear cell infiltrates in cyclosporine (CsA) vs. azathioprine-treated patients revealed significantly fewer Leu 2 (P less than .05) and Leu M1 (P less than .05) cell populations in CsA patients during acute rejection. In 32 of these 72 biopsies (44.4%), the biopsy results provided a direct contraindication to the use of steroids, by allowing differentiation between allograft rejection and other causes of graft dysfunction. A total of 38% of the biopsies yielded a histological diagnosis that contradicted the clinical pre-biopsy diagnosis. All allografts showing evidence of severe small vessel disease and/or antibody-mediated rejection eventually were lost. These data highlight the usefulness of needle biopsy material as a guide to the study of intragraft immune events and to clinical management of recipients. PMID- 3099441 TI - The protective effect of calcium inhibitors and of captopril on the renal microcirculation during reperfusion. AB - Reperfusion injury is increasingly recognized as a key factor in the development of posttransplant acute tubular necrosis. Previous studies have shown that addition of the calmodulin inhibitor trifluoperazine (TFP) to Collins' flush solution protected the cortical microcirculatory integrity and dramatically improved renal viability after transplantation. The present report describes the protective effect(s) of TFP in the course of reperfusion injury. Twenty mongrel dogs underwent bilateral nephrectomy; in each instance, the left kidney was flushed immediately with 250 ml of cold Collins' solution, and the right kidney was flushed with the same solution containing TFP, 5 mg/L. After 48 and 72 hr of preservation, each kidney was connected through silastic shunts to the femoral vessels of another dog. The mean renal blood flow (RBF) immediately after reperfusion was 2.2 ml/g/min and 1.7 ml/g/min in the left and right kidneys, respectively, and was similar to mean RBF measurements prior to nephrectomy. After 15 min of reperfusion, there was a sharp decrease in mean RBF in the Collins' flushed kidneys, which persisted after 60 min of reperfusion (0.37 ml/g/min). In contrast, there was only a mild decrease in mean RBF in the TFP flushed kidneys (1.27 ml/g/min). A partial explanation for the favorable effect of TFP may be related to the inability of the ischemic cell to handle the increased calcium load associated with reperfusion (calcium paradox). In a test of this possibility, 0.5 mg/kg of verapamil, a calcium channel blocker, was infused during reperfusion. No beneficial effects of this drug were noted in either Collins' or TFP-flushed kidneys (n = 10). However, when 1.25 mg/kg of captopril, an angiotensin-converting enzyme inhibitor, was infused at the time of reperfusion, a dramatic amelioration of the reperfusion injury occurred in the Collins' flushed kidneys (1.2 ml/g/min) (n = 10). Taken together, these data suggest that the damage to cold-preserved kidneys flushed with Collins' solution alone may occur at the time of actual reperfusion. Such reperfusion damage is ameliorated by TFP and captopril. The known relationship between calcium and the effect of angiotensin on the vascular smooth muscle cell may explain in part the protective role of calcium inhibitors placed in preserved kidneys prior to reperfusion. PMID- 3099442 TI - A randomized clinical trial comparing OKT3 and steroids for treatment of hepatic allograft rejection. AB - A multiinstitutional randomized trial was undertaken comparing OKT3 with steroids for treatment of hepatic allograft rejection. All patients received baseline immunosuppression with Cyclosporine (CsA) and steroids. At the time of biopsy confirmed rejection, up to 2 intravenous boluses (250-1000 mg) of methylprednisolone were initially administered. Twenty-eight patients who failed to respond were then randomly assigned to OKT3 or continued steroid therapy. Rescue therapy with the opposite treatment arm was added after 6 days if the primarily allocated protocol failed. Three of 13 patients assigned to the steroid group responded promptly, and continue with good function 7-12 months later. OKT3 rescue was required in 10 patients who failed to improve despite receiving up to 6 g of methylprednisolone (mean: 3.3 g/patient). One patient died of sepsis and hepatic failure. Rejection was reversed in 9 OKT3-rescue patients, 7 of whom are well 1-17 months later. In the OKT3 group, improved allograft function was observed within 72 hr in 11 of 15 patients. Two patients with inadequate response were successfully rescued with steroids; 1 patient underwent retransplantation; and 1 patient developed a biliary fistula that eventually resulted in sepsis and death. In summary, 23 of 28 hepatic recipients (82%) are alive with the original allograft 1-17 (mean 7.8) months after treatment for acute rejection. Another patient is alive 14 months following retransplantation. Eighteen (78%) of the survivors required OKT3 as initial (11) or rescue (7) therapy, whereas only 5 were successfully managed with steroids. OKT3 is superior to steroids for reversing liver allograft rejection and has greatly reduced the need for retransplantation even in recipients selected on the basis of having failed initial steroid therapy. PMID- 3099443 TI - [Isolation of the proteolytic complex from industrial waste waters from streptomycin production]. AB - Dynamics of industrial biosynthesis of polyenzymic Streptomyces griseus system proteases and changes in their activities are studied in the process of streptomycin production. The method to isolate protease preparations is developed with optimization of production cycles of the stabilization, vacuum concentration, ballast protein salting-out and lyophilization stages. The preparation is low toxic, retains 98% of the proteolytic activity at the temperature of 60 degrees C, 30 and 80%--under the effect of EDTA and urea, the activity maximum is at pH 7.0-8.0. The production technique of the preparation is estimated for its economic efficiency. PMID- 3099444 TI - [Health and automobile driving. Preliminary cost-benefit study]. PMID- 3099445 TI - Effects of a potent LHRH-agonist on the pituitary gonadal axis with and without testosterone substitution. AB - In this study we investigated the effect of low and high dosages of a potent LHRH agonist on the pituitary-gonadal axis with special consideration to the effect on the tubular compartment of the testis. Included were 3 treatment groups: the probands in Group I were treated with 3 X 50 micrograms HOE 766/week intranasally for 5 months; in Group II with 3 X 100 micrograms HOE 766 intranasally/day for 6 months and in Group III with 3 X 200 micrograms HOE 766 intranasally plus 5 mg fluoxymesterone orally/day for 5 months. With the low dose (Group I) no changes in the seminal parameters measured could be observed whereas LH and FSH levels increased in plasma, testosterone showed no change compared to pretreatment values. When high dosages/day of a potent LHRH agonist were administered without androgen replacement (Group II) pronounced decrease of LH and FSH took place, the testosterone plasma levels approached the female range. Spermatogenesis was arrested. The agonist plus androgen replacement (Group III) counteracted the suppression of spermatogenesis. PMID- 3099447 TI - HCG and HMG treatment of male infertility with pituitary problems. AB - A case is presented of a twenty-nine-year-old acromegalic man with sexual problems and fertility disturbance due to pituitary adenoma, who successfully fathered. Various endocrinologic studies, skill x-ray film, and computerized tomography (CT) scan revealed a pituitary adenoma. Testicular biopsy specimen also supported that the cause of sexual problems and fertility disturbance was secondary in origin. One month after transsphenoidal pituitary adenectomy, administration of human chorionic gonadotropin and human menopausal gonadotropin was started. His potency was improved immediately after start of the treatment, and his wife became pregnant five months later. PMID- 3099448 TI - [Reasons for relaparotomies following operations on the biliary tract in nontumorous lesions]. AB - According to the authors' data the incidence of relaparotomies after 1500 operations for non-tumor diseases of bile ducts was 2.5%. Causes of relaparotomies at early and late terms of the postoperative period were different. The dependence of results of the treatment on the amount of relaparotomies and the presence of such complications as jaundice, cholangitis and pancreatitis has been established. In such complications and increased amount of relaparotomies lethality was considerably higher. General lethality after relaparotomies was 49%. Complex of prophylactic and curative measures of the complications resulting in relaparotomies has been developed. PMID- 3099446 TI - Post-ischemic renal function after kidney protection with the HTK-solution of Bretschneider. AB - The cardioplegic solution HTK of Bretschneider was used for canine kidney protection. The kidneys were perfused with this solution for 6-10 min prior to the induction of ischemia. The kidneys were left in-situ for 60, 90, 120 and 135 min ischemia time at a temperature of 25-34 degrees C (n = 13). As a control group we used unilateral nephrectomized dogs (n = 9). After unilateral nephrectomy an elevated plasma creatinine in comparison to preoperative values was observed. After 60 and 90 min under HTK-protection the postoperative plasma creatinine was not elevated compared to the control group. After 120 min of ischemia creatinine level was slightly increased to an average of 2.1 mg% on the first and second postoperative day. These experiments indicate the protective effect of the cardioplegic solution for canine kidney preservation in situ. PMID- 3099449 TI - [Choice of the surgical intervention method in peptic ulcer combined with diverticula of the stomach and duodenum]. AB - Diverticula of the stomach and duodenum were revealed in 21 (2.3%) of the examined patients with ulcer disease. Resection with radical interventions on the diverticulum were fulfilled in 8 patients, with by-passed duodenum in 7 patients, with selective proximal vagotomy associated with invagination of the diverticulum in 6 patients, among them 1 patient with a subpyloric Y-shaped bypass of the duodenum. There were no lethal outcomes. PMID- 3099450 TI - Evaluation of the microtitre spin agglutination assay in the diagnosis of bovine brucellosis. PMID- 3099451 TI - Experimental microcyst sarcocystis infection in lambs: serology and immunohistochemistry. AB - Density gradient centrifugation using a performed self generated gradient of colloidal silica enabled the isolation of microscopic sheep sarcocystis cystozoites, free from heart muscle contamination. The efficiency of separation of cystozoites from residual heart muscle after digestion in pepsin and hydrochloric acid was 63 to 92 per cent. Antigens from cystozoites were used on enzyme-linked immunosorbent assays (ELISA) of plasma from six coccidia-free lambs infected once orally with 70,000 microcystic sheep sarcocystis sporocysts and for raising antisera in rabbits. Use of an anti-sheep IgM conjugate in the ELISA showed that anti-sarcocystis IgM production was transitory, appearing five to 10 days after infection, peaking in concentration at 42 days and following the peak of the acute phase of infection (32 and 33 days) in the lambs. In contrast, total anti-sarcocystis immunoglobulins, detected by ELISA, increased from five to 21 days after infection and continued to increase until the lambs were killed (the last at 81 days) and was more useful in diagnosing chronic infection. No cross reactions between microcystic sheep sarcocystis and Toxoplasma gondii or Eimeria species of sheep were observed. A peroxidase anti-peroxidase test, using rabbit anti-sarcocystis sera, detected second generation meronts and sarcocysts in fixed tissues from infected lambs making it useful for the diagnosis of acute or chronic disease post mortem. PMID- 3099452 TI - [Complicated diverticulum of the stomach]. PMID- 3099453 TI - Production and characterization of monoclonal antibodies raised against BoLA class I antigens. AB - Monoclonal antibodies (MoAbs) reacting with bovine leukocyte membrane antigens have been prepared by fusion of mouse myeloma cells (SP2/0.Ag.14) and spleen cells of mice immunized with various cell types. Three of these MoAbs detected membrane components showing the typical structure of class I MHC molecules; indeed, immunoprecipitation studies revealed that these components were proteins composed of two subunits of 44,000 and 12,000 daltons apparent molecular weight. The density of these antigens in the cells of various leukocyte lineages was determined by solid phase radioimmunoassay, immunogold staining and cytofluorometry. Their expression seemed similar to that of class I molecules in other species, namely heavy on the mononuclear blood cells and weaker on the neutrophils and platelets. The eosinophils appeared more positive than the neutrophils, while the erythrocytes were negative. Cross-inhibition and sequential immunoprecipitation experiments demonstrated that these MoAbs recognised different epitopes either on a single molecule or on cross-reacting molecules. One antibody appeared to be raised against the monomorphic bovine beta 2-microglobulin, while the two other antibodies detected the heavy chain of polymorphic class I-like products. The authors propose that the BoLA class I polymorphism should be studied by determination of the fixation ratio of the monomorphic anti-beta 2M versus the polymorphic anticlass I antibodies amongst the animals. PMID- 3099454 TI - A morphometrical analysis of dysplasia in small adenomas of the large intestine. AB - In a morphometrical study of 40 colorectal adenomas less than 10 mm in diameter and of 10 specimens of normal mucosa, it was found that nuclear size, perimeter and shape-factor of the epithelial cells were significantly different in neoplastic when compared with normal tissues. The same was found for the volume fraction of stroma, gland spaces, goblet and non-goblet epithelium, for the gland diameter, nuclear stratification height and stratification index, but not for the epithelial height nor the total volume fraction of the epithelium. In a multivariate analysis, stratification index and nuclear size of the epithelial cells contributed most significantly to determination of the histological grade of dysplasia in adenomas. By the combination of these two morphometric variables 75% of all adenomas could be correctly allocated to the grade of dysplasia. PMID- 3099455 TI - Immunocytochemical study of human lymphoid tissues with monoclonal antibodies against S-100 protein subunits. AB - The present study concerns the immunocytochemical localization of S-100 protein alpha and beta subunits in the cells of human lymphoreticular tissue and their related tumours. The alpha subunit is mainly localized in dendritic cells, most likely the dendritic reticulum cells (DRCs) located within the germinal centers, while the beta subunit is mainly localized in the interdigitating reticulum cells (IRCs) in the paracortical area and in Histiocytosis "X" cells. No immunoreactivity for either subunit was found in the majority of normal lymphocytes, macrophages, malignant lymphoma cells, or xanthoma cells. The DRCs and IRCs are generally considered to show different distribution in the lymphoid tissues and demonstrate some difference in their immunocytochemical and enzyme histochemical features. It is suggested that S-100 subunits can be used as useful markers for these two types of dendritic cells and investigation of these subunits may provide more information for the study of human lymphoreticular system. PMID- 3099456 TI - Analysis of viral antigens in giant cells of measles pneumonia by immunoperoxidase method. AB - The localization of measles virus proteins was analyzed by immunoperoxidase method using both monospecific and monoclonal antibodies. In Vero cells infected with the Edmonston or EB-L strain, the former being a laboratory strain and the latter a fresh isolate from a measles patient, nucleocapsid protein was located in the nuclei, and matrix protein, phosphoprotein, haemagglutinin and fusion protein were located in the cytoplasm. In the lung tissues of eight cases with measles giant cell pneumonia, the similar findings were obtained. The presence of haemagglutinin on the surface of giant cells at the luminal side was also noticed. Histopathologically, measles giant cells had nuclear and cytoplasmic eosinophilic inclusion bodies with some differences in appearance. The significance of localization of viral proteins is discussed in comparison with histopathological findings in measles giant cells. PMID- 3099457 TI - Light and electron microscopic demonstration of neuropeptide Y-like immunoreactive nerves in human cardiac muscle. AB - Neuropeptide Y (NPY)-like immunoreactive nerves were demonstrated in human cardiac muscle. The atrial specimens were obtained from open-heart surgery. The PAP method was applied for immunocytochemistry for light and electron microscopy. A dense, extensive network of NPY-like immunoreactive nerve fibres was seen between cardiac muscle cells and around blood vessels. In electron microscope PAP precipitates were localized in large dense-cored vesicles of 80-120 nm in size in separate nerve terminals or in the terminals situated in the nerve bundles. Close contacts were observed between NPY nerves and muscle cells and blood vessels. The possible functional role of NPY innervation in the human heart is discussed. PMID- 3099458 TI - Dimensional changes of proximal tubules and cortical capillaries in chronic obstructive renal disease. A light microscopic morphometric analysis. AB - The study was carried out to determine the proximal tubular length, surface area and length of peritubular capillaries and the nephron numbers in kidneys with chronic nephropathy and varying increase in the cortical interstitial volume. Kidneys of pigs with varying chronic obstructive nephropathy were used for the experiments. Two subgroups of ureter-obstructed kidneys were defined arbitrarily according to the volume of cortical interstitium. One subgroup (I) comprised kidneys with a volume fraction of cortical interstitium less than 30% (mean 17.2%; mean of controls 9.7%). The other subgroup (II) consisted of kidneys with severe chronic nephropathy and with a volume fraction of interstitium more than 30% (mean 44.5%). Proximal tubular length and length and surface area of peritubular capillaries were assessed by conventional morphometric techniques on 1 micron thick sections of plastic embedded material. Nephron numbers were determined by a stereological method for counting glomeruli. The results demonstrated that proximal tubular length and capillary dimensions were significantly reduced in subgroup II, whereas no significant changes were observed in subgroup I. The mean number of glomeruli was not significantly different from control values in any of the subgroups. The results are in line with observations from previous quantitative analyses of proximal tubular cross sections indicating that proximal tubular dimensions become reduced mainly at advanced stages of chronic nephropathy. The results also indicate that shortening of individual tubules rather than loss of entire nephrons is responsible for the observed reduction in total length of proximal tubules. Finally, the present observations suggest that reduced dimensions of the cortical capillary network may have pathogenetic significance for ongoing proximal tubular atrophy in chronic renal disease. PMID- 3099459 TI - Monoclonal antibodies recognizing lipid-laden cells and extracellular regions with lipid-deposits in atherosclerotic aorta. AB - Monoclonal antibodies against lipid-laden cells and against extracellular regions of lipid-deposits in atherosclerotic aorta were prepared. Mice were immunized with a delipidated homogenate of atherosclerotic aorta of Watanabe-heritable hyperlipidemic rabbits. Hybridomas were obtained by fusion and cultured in hypoxanthine, aminopterin and thymidine selection medium. Specific antibodies were selected by indirect immunohistochemical staining of frozen sections of atherosclerotic aorta. Nine clones that produced antibodies that stained the atherosclerotic intima exclusively were selected and cloned by limiting dilution. Finally two clones (FCR1a/201F, FCR1b/904B) producing antibodies specific to lipid-laden cells and one clone (EMR1a/212D) producing an antibody specific to regions with lipid deposits in the extracellular matrix were established. These monoclonal antibodies may help in understanding how lipids accumulate in atherosclerosis. PMID- 3099460 TI - Buschke-Loewenstein tumour. A histologic and ultrastructural study of six cases. AB - Results on the light- and electron microscopic studies of six cases of Buschke Loewenstein tumour are presented. The role of chronic irritation is emphasized in the aetiology of the tumour. Fistulas and abscesses arising in the tumour are dangerous as they give rise to chronic sepsis. In two perianal tumours, in situ or invasive carcinoma developed. Electron microscopy revealed varying degrees of differentiation of keratinocytes. As a result of the defective desmosomes, the tumour cell underwent segregation, with widened intercellular spaces containing oedema, erythrocytes and leucocytes. This phenomenon is probably responsible for frequent bleeding and fistula formation. The investigations disclosed that the Buschke-Loewenstein tumour is a special form of squamous carcinoma and therefore, radical surgical excision must be attempted even in case of a benign histological picture. PMID- 3099461 TI - Heterogeneity in a colonic carcinoid tumor. AB - This report describes a colonic carcinoid tumor in which three, and possibly four, distinct cell types are distinguishable on the basis of their ultrastructure and granule morphology. These cell types closely resemble the normal endocrine cells of the large bowel, both in appearances and in relative frequency. The mixed composition of this tumor may have arisen either by parallel differentiation of distinct cell types, or by sequential maturation of one cell type. PMID- 3099462 TI - Mixed hyperplastic and neoplastic polyp of the colon. An immunohistological study. AB - A small colonic polyp which was composed of equal parts of hyperplastic and adenomatous tissue sharing a common basement membrane, displayed a paradoxical distribution of immunohistological markers: In contrast with the neoplastic component, the hyperplastic tissue lacked signs of functional maturity (IgA, secretory component) and displayed markers associated with carcinoma (carcinoembryonic antigen, peanut-agglutinin binding). PMID- 3099464 TI - The sinusoids in cirrhosis. A morphometric study. AB - The volume fraction of the sinusoids (Vv), the sinusoidal surface:total volume ratio (Sv), and the sinusoidal length:total volume ratio (Lv) were evaluated morphometrically in twelve biopsy specimens with cirrhosis and in eleven control specimens. The Sv, which is directly related to the radius of the sinusoids, was significantly (0.01 greater than P greater than 0.001) greater in the cirrhotic group than in the controls. In contrast, the Lv, which is directly related to the length of the sinusoids, and the Vv did not vary significantly in the same groups. These data support the concept that changes of the sinusoids do not contribute to portal hypertension in cirrhosis. PMID- 3099463 TI - Evidence of vascular differentiation in anaplastic tumours of the thyroid--an immunohistological study. AB - Sixteen cases of anaplastic carcinoma (ACA) and 4 cases of malignant haemangioendothelioma (HAE) of the thyroid were studied by light microscopy and immunohistochemistry. Seven cases of ACA and 3 cases of HAE were characterized by coexpression of immunohistological features of epithelial and vascular endothelial cells. Expression of vimentin was common to all tumours investigated. The present study provides evidence that ACA and HAE are partially closely related tumours showing alternating differentiation. This speaks in favour of a common neoplastic cell with the potential for epithelial and vascular endothelial differentiation. PMID- 3099466 TI - Serotonin in tubular adenomas, adenocarcinomas and endocrine tumours of the stomach. An immunohistochemical study. AB - Serotonin was examined immunohistochemically in seven tubular adenomas, 194 adenocarcinomas and 41 endocrine cell tumours of the stomach. In tubular adenomas, serotonin-containing cells showing argentaffinity were present in the lower portion of the adenomatous glands and were considered to be an expression of intestinal character. Scattered serotonin-containing tumour cells were found in 60 (30.9%) of 194 adenocarcinomas regardless of their histological type. Cell fusions between carcinoma and enterochromaffin (EC) cells might be a possible mechanism for the occurrence of serotonin-containing cells within the tumour. In 17 (54.8%) of 31 endocrine cell carcinomas, serotonin-containing tumour cells were observed in a variable degree in contrast to the absence of these cells in classical carcinoid. Moreover, diffuse serotonin reactivity was found in four cases of scirrhous endocrine cell carcinoma. The histogenesis and the occurrence of serotonin-containing cells in each type of gastric tumour is also discussed. PMID- 3099465 TI - Studies on fine structure and location of lipids in quick-freeze replicas of atherosclerotic aorta of WHHL rabbits. AB - The fine structure of intracellular and extracellular lipids in the atherosclerotic aorta of Watanabe-heritable hyperlipidemic (WHHL) rabbits was demonstrated by a quick-freeze etching technique. Many lipid droplets, with and without a membrane, were observed in the foam cells. Membrane-free droplets were observed as onion-like structure with a concentric lamellar structure surrounded by 10 nm filaments. Droplets surrounded by a limited membrane probably correspond to lipid-laden lysosomes. In the extracellular connective tissue space, marked accumulation of lipids with a vesicular structure was seen among collagen fibers. The appearance of these lipids was similar to that of lipids in lysosomes of foam cells. PMID- 3099467 TI - [Current problems in the epidemiology and prevention of viral hepatitis non-A, non-B (a review of the literature)]. PMID- 3099468 TI - [Role of Pseudomonas aeruginosa in the etiology of infectious complications in cancer patients]. AB - The occurrence of Pseudomonas aeruginosa in various pathologic materials and feces from patients with different cancer was compared. The rate of Pseudomonas aeruginosa-associated postoperative complications versus the frequency of intraoperative detection of the organism was studied. The sensitivity of Pseudomonas aeruginosa to antibacterial drugs was assessed. Serotypes of 480 strains isolated from patients and environment were identified. It was inferred that exogenous contamination from the external environment accounts for the majority of cases of Pseudomonas aeruginosa-associated complications. PMID- 3099469 TI - [Effect of the type of nutrition and aflatoxin B1 on the structure of chromosomes]. AB - Deficiency of the essential nutrients lysine, methionine, threonine and vitamins A, E, C significantly increases the mutagenic environment of somatic cells in growing Wag rats. Aflatoxin B1 produces a pronounced mutagenic effect on the cellular genetic apparatus; this effect is substantially modified due to the nutrition character: it is either intensified or inhibited. The results obtained suggest that the nutritional factors can de used for prevention and elimination of aflatoxin B1-induced mutations. PMID- 3099471 TI - Screening of factor VIII:C levels in blood donors. AB - A new chromogenic peptide substrate method, modified for assay with semi-micro tubes, Cobas Bio centrifugal analyser and microplates, was used for screening of F VIII:C in blood donors. The precision of the assays is high and the costs are reasonable. The assay with microplates is especially suitable for selection of donors for a plasma programme and for quality control in blood banks. PMID- 3099470 TI - Opsonic and complement-dependent bactericidal activities of various immunoglobulin preparations for intravenous use. AB - Some effector functions of various immunoglobulin (IgG) preparations have been compared. Tests for opsonic activity were performed in vitro with human peripheral blood leukocytes and in vivo with mice. The augmentation effects on luminol-dependent chemiluminescence were investigated with human leukocytes. The complement-dependent bactericidal activities were tested with Escherichia coli. Five IgG preparations: pH 4-treated preparation (IG-100), polyethyleneglycol treated preparation (PEG-G), sulfonated preparation (S-G), pepsin-treated preparation (Pep-G) and a preparation for intramuscular use (GGN) were studied. The results were as follows: (1) IG-100 and PEG-G exhibited strong activities in all test systems; (2) GGN showed a strong opsonic activity; (3) S-G showed relatively weak activities in all test systems, but the revertant S-G preparation exhibited somewhat stronger activities in all systems, and (4) Pep-G showed weak or no activity in all systems. These results suggest that the IgG molecules in IG 100 and PEG-G preparations have satisfactory effector functions. On the other hand, IgG molecules in S-G and Pep-G preparation may have significant deficiencies in their biological functions. PMID- 3099472 TI - Lymphocyte killer activity in individuals sensitized against antigen-D assessed by direct ADCC lysis of O,Rh-positive erythrocytes. AB - Lymphocytes from individuals sensitized against the Rh-D antigen were found to lyse O,Rh-positive erythrocytes. The controls consisted of individuals non sensitized against D antigen. The lytic effect in the absence of additional in vitro added specific antibody was very high in sensitized individuals, but low in the control group. Lytic effect decreased after treating the lymphocytes of sensitized donors with trypsin, but it remained unchanged in the control group. These results suggest that the sensitized donors possessed lymphocytes with specific antibodies in vivo. This phenomenon could prove a valuable diagnostic tool in recognizing responder and non-responder donors in the early phase of immunization. PMID- 3099474 TI - Rhesus Du incompatibility in a newborn without hemolytic disease: a possible role for the mononuclear phagocyte system in the benign clinical course. PMID- 3099473 TI - Reduced survival of isotope-labelled Rh(D)-negative donor red cells in a patient with anti-LWab. AB - The serum of an 85-year-old Caucasian male with no history of blood transfusion contained an IgG3 antibody with anti-LWab specificity. The antibody failed to react with dithiothreitol-treated red cells, and there was a marked reduction in titre of the antibody with pronase-treated cells, findings consistent with an antibody having this specificity. High association values were obtained in a mononuclear phagocyte assay when LW-positive red cells, sensitised in vitro with the patient's serum antibody, were incubated with peripheral blood monocytes from the patient. In vivo red cell survival studies demonstrated that 99mTc-labelled rhesus-negative (rr), LW-positive red cells had 53% survival at 1 h. The IgG subclass of the antibody, mononuclear phagocyte assay results and in vivo survival studies predicted a significant reduction in the posttransfusion survival of therapeutic volumes of rhesus-negative (rr), LW-positive red cells. PMID- 3099475 TI - [Evaluation of the results of a direct solid-phase immunoenzyme method for determining antigens]. AB - Aspects of an objective analysis of the results of solid-phase enzyme-immunoassay (SPEIA) for identification of antigens (a direct version) were considered on the model of the virus of hemorrhagic fever with renal syndrome. Using a statistical method, certain parameters of 11 types of polystyrene and polyvinylchloride microplates (solid carrier) of different manufacturers were studied from the point of view of their suitability for obtaining reproducible SPEIA results. Statistical methods for the evaluation of EIA data are proposed to increase the effectiveness of the use of this test and making it quite an objective one. PMID- 3099476 TI - [Biological and physicochemical properties of Corynebacterium diphtheriae B (Freeman) phages phi 984 and phi 9]. AB - A scheme for preparative isolation of corynephages and their DNA is described. Study of host specificity, toxigenicity, and of cytotoxic effect induced by the phages BF, phi 9, and phi 984 has shown that phage BF has tox- phenotype, and phages phi 9 and phi 984, tox+ phenotype. These phages differ in host specificity and plaque morphology. Electron-microscopic examination of virions showed similarity of phages BF and phi 984 structures, whereas phage phi 9 was markedly different in the size of its head and tail. PMID- 3099478 TI - Regulatory mechanisms for nursing training and practice: meeting primary health care needs. Report of a WHO Study Group. PMID- 3099479 TI - Epidemiology and control of African trypanosomiasis. Report of a WHO Expert Committee. PMID- 3099477 TI - [Antiviral and immunostimulating effect of maleic anhydride copolymers in experimental neuroviral infections]. AB - The virus-inhibiting and immunostimulating activity of Soviet preparations, maleic anhydride copolymers, was demonstrated in alpha-, flavi-, and bunyavirus infections. Positive results were obtained in subcutaneous and intraperitoneal inoculations of the preparations used in prophylactic and therapeutic prophylactic schedules. Stimulation of vaccination immunity was observed after combined use of copolymers and the vaccine against Eastern equine encephalomyelitis. PMID- 3099480 TI - [Modification of plasma blood coagulation factor activity by physical stress]. AB - The influence of physical stress (bicycle ergometer and track) on 13 parameters of the plasmatic coagulation system was investigated in trained and untrained test persons. Shortenings of the coagulation times as well as distinct increases of the activity or concentration were observed in the partial thromboplastin time (PTT), the factor VIII activity (VIII:C) and the factor VIII-associated antigen (VIIIR:Ag). The results are discussed with regard to their causes and their clinical importance. PMID- 3099481 TI - Effects of nitrates in various vascular sections and regions. AB - Recently there has been much progress towards defining the action of nitrates, and related compounds, at a biochemical level. However, in vivo, differences in the effects of nitroglycerin (GTN) between specific sections of the vascular tree and various regions of the circulation are still not well understood. The actions of nitrates as they relate to the alleviation of myocardial ischemia are briefly reviewed. Then, an attempt is made to analyze separately the nitrodilator influences in the large and medium sized arteries, the venous system and the arterioles, in vivo. When pitfalls such as nonselectivity of indexes of drug action and secondary compensatory regulatory influences are considered, a surprising responsiveness of the resistance vessels to GTN is unmasked, revealing a remarkable uniformity in the profile of GTN action within different sections of the vascular tree. Nitrate effects in these vascular sections are then compared among several important regions of the circulation (i.e. mesenteric, skeletal muscle, brain etc.), and similarities or differences in action are noted. Finally the concepts presented here are related to some areas of controversy regarding nitrate action, in an attempt to form a basis for a better understanding of the sometimes confusing nitrate literature. PMID- 3099482 TI - [Transdermal nitroglycerin in the treatment of pulmonary hypertension]. AB - In 10 patients with pulmonary hypertension, glycerol trinitrate in patch form (DEPONIT 10) effected a statistically significant drop in pulmonary artery pressure, pulmonary capillary pressure and right atrial pressure within 24 hours following drug application. This pressure reduction was also recorded after 4 weeks of continuous therapy. The reduction of pulmonary artery pressure and pulmonary vascular resistance is not only a consequence of improved pre- and afterload, but also of a decrease in respiratory tract resistance and a direct influence on arteriolar constriction in the pulmonary vascular bed. Beneficial effects upon pulmonary haemodynamics were also recorded several months later. PMID- 3099483 TI - Relationship between pharmacokinetics and pharmacodynamics of organic nitrates. AB - The pharmacological effect of drugs can usually be described as a dose- or concentration-response relationship. With respect to organic nitrates there are many confounding factors which can modify or even mask the existence of such a relationship. The antianginal effect of these drugs is the result of hemodynamic changes caused by their action on different parts of the vascular system. These effects are thought to have different concentration-response relationships and to participate to a different degree in the antianginal efficacy. Counterregulatory mechanisms and development of tolerance may further modify these concentration response relationships. The formation of active metabolites makes it necessary to consider each drug species separately with respect to the time course and magnitude of effect. Evidence also exists that for glycerol trinitrate the time course of drug concentration at the site of action may be different from that in the plasma. Furthermore, not only the actual plasma concentration but also its rate of change may determine the magnitude of effect. This can cause the efficacy to depend also on the route of administration. Therefore, it is not surprising that for organic nitrates large intersubject differences exist in the plasma concentration-response relationship and that it is difficult to define a therapeutic plasma concentration range. PMID- 3099484 TI - Nitrosothiol and nitrate tolerance. AB - Our studies on Sprague-Dawley rats showed that, in aortic tissues, nitrate tolerance is accompanied by reduced production of the 1,2-glyceryl dinitrate metabolite. This reduced vascular metabolism is consistent with the view that intracellular metabolic processes occur prior to vasodilation. The individual roles of the denitrated metabolites in nitrate tolerance are still unclear. S nitroso N-acetyl penicillamine retains its vasodilating properties toward blood vessels which have been made tolerant toward nitroglycerin. This finding is consistent with the Ignarro Nitrosothiol Hypothesis for nitrate action. Further studies are being conducted in our laboratory to determine whether nitrosothiols are indeed non-tolerance producing "nitrates" and whether they possess suitable pharmaceutical and toxicological properties for them to become therapeutic agents themselves. PMID- 3099485 TI - Acute effects of nitrates on left ventricular performance and energetics. AB - Left ventricular myocardial performance and efficiency were analyzed on the basis of two new energetic parameters in patients with coronary heart disease. The myocardial energy consumed during one cardiac cycle is related on the one hand to the work performed (E1) and on the other to the stress-time integral (E2). E1 was obtained by analysis of the pressure-volume integral divided by the left ventricular muscle mass. E2 was obtained as follows: The stress-time integral was analyzed from pressure-volume data and wall thickness using an ellipsoidal calculation model. In order to transfer the stress-time integral into energy units, the value is multiplied by a constant factor which was obtained experimentally in myothermal studies. In patients with coronary heart disease, a single dose of nitroglycerin (1.6 mg s.l.) reduced the total energy sigma (E1 + E2) from 6.1 mcal/g to 4.7 mcal/g (n = 10; P less than 0.01). The efficiency of myocardial contraction (E1/sigma (E1 + E2] was not changed significantly. These data explain quantitatively the beneficial effect of preload and afterload reduction due to nitroglycerin. PMID- 3099486 TI - [Dose-response relationship of nitrate therapy of angina pectoris]. AB - The treatment of 15 patients with coronary heart disease and exertion-related angina pectoris with isosorbide dinitrate (ISDN) tablets in 4 doses (6 X 5 mg, 6 X 20 mg, 6 X 40 mg, 6 X 80 mg) in a randomized sequence for 1 week each resulted in a dose-related improvement of ischemia (ST-segment depression during stress testing) as compared to placebo: 5 mg (30 mg/day): 24% (p less than 0.05); 20 mg (120 mg/day): 40% (p less than 0.05); 40 mg (240 mg/day): 60% (p less than 0.01); 80 mg (480 mg/day): 74% (p less than 0.01). Continuation of treatment for another 4 weeks with 480 mg/day led to a slight decrease in antianginal activity, with a 55% improvement of ST-depression. The frequency of angina pectoris was also lowered in a dose-related manner. For nitroglycerin in oral sustained release form (matrix system) a dose-related antianginal efficacy could be demonstrated in 12 patients enrolled in a double-blind cross-over trial: 2.6 mg (single dose): 23% (n.s.); 6.5 mg: 38% (p less than 0.01); 10 mg: 55% (p less than 0.001); 20 mg: 74% (p less than 0.0001). The duration of action of 20 mg was 4 hours. Transdermal nitroglycerin also proved to be effective in a dose related fashion. In 12 patients undergoing 1-week treatment periods with 5 cm2, 10 cm2 and 20 cm2 patches ST-depression was favourably influenced by 15% (n.s.), 22% (p less than 0.05) and 46% (p less than 0.001) 3 hours after administration. No antiischemic efficacy was demonstrable 24 hours after medication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099488 TI - [Hemodynamic effect and duration of action of Deponit 10 in patients with congestive heart insufficiency]. AB - The haemodynamic effect of transdermal nitroglycerin treatment with Deponit 10 was investigated in 10 patients with chronic cardiac failure due to coronary artery disease (8 patients) or congestive cardiomyopathy (2 patients). The patients had elevated mean pulmonary artery (PA) and pulmonary capillary wedge pressures (PC) at rest (32.1 +/- 5.9 and 24.1 +/- 6.6 mm Hg). Heart rate (87 +/- 10), arterial blood pressure (133 +/- 20/77 +/- 8 mm Hg) and cardiac index (3.73 +/- 0.85 l/min/m2) were in the normal range. During treatment with Deponit 10 mean PA and PC pressures decreased significantly (p less than 0.01) to 25.5 +/- 6.3 and 18.1 +/- 6.4 mm Hg, respectively. The effect was seen within 1 hour after application of the transdermal therapeutic system and reached its nadir after 2 hours. PA and PC pressures remained significantly below control for 12-16 hours. Heart rate, arterial blood pressure and cardiac index were not changed. After removal of the patch 4 patients showed a rebound haemodynamic deterioration. Their mean PA pressure rose by more than 4 mm Hg above the respective control values. These patients had the highest control PA pressures of the group studied (37.5 +/- 2.4 mm Hg). Thus, transdermal nitroglycerin treatment with Deponit 10 reduces cardiac preload in patients with congestive heart failure for 12-16 hours, whereas cardiac afterload remains unaffected. After removal of the patch a rebound phenomenon can occur especially in patients with severe cardiac failure. PMID- 3099487 TI - [PLacebo-controlled double blind study of the anti-ischemic efficacy of transdermal depot nitrate]. AB - Twelve patients with stable angina pectoris were studied in a randomized double blind cross-over placebo-controlled manner utilizing exercise testing and measurement of ST-segment depression before, 2, 6 and 24 hours after application of a transdermal system delivering 5 mg or 10 mg nitroglycerin per day. All testings were performed at a constant work load and exercise time. Significant improvement of ST-segment depression was only seen at 2 hours (5 mg: -45%, 10 mg: -55%) and 6 hours (5 mg: -16%, 10 mg: -31%) but not at 24 hours. The lack of efficacy at 24 hours appears to be due to tolerance. PMID- 3099489 TI - Acute and chronic efficacy of low-dose nitroglycerin patches in stable angina pectoris. AB - In a single-blind placebo controlled study, acute and chronic efficacy of low dose nitroglycerin patches (NTG 5 mg/day) was studied in 24 patients with stable angina pectoris. NTG patch effects were evaluated by means of the multistage treadmill exercise test. During the acute study one exercise test was carried out after the wash-out period, after placebo patch (5 hours after application) and NTG patch (5, 16, 20 and 24 hours after application), so that a 3 day wash-out period had preceded each exercise test. Afterwards, chronic NTG patch therapy was continued for three months. At the end of this period exercise tests were carried out, in three day intervals of therapy, 5, 16, 20 and 24 hours after therapy. Then, a 7 day placebo patch period was continued with one exercise test at the end, 5 hours after application. Statistical analysis was carried out by multivariate analysis of difference. Systolic and diastolic blood pressure at rest fell significantly only in the acute 5 hour measurement, with no change in the other periods. The NTG patch augmented significantly mainly all heart rate values during exercise test, with no change in resting values. Placebo, acute and chronic exercise tests did not show any significant difference. They showed a slight but significant placebo influence on the exercise test compared to the wash-out period, improving maximum walking time and time to the onset of angina pectoris but with worsening of maximum ST-depression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099490 TI - Effects of short- and long-term treatment with transdermally and orally administered nitroglycerin (a double-blind crossover study). AB - The efficacy of a once daily transdermally applied nitroglycerin system and of sustained release nitroglycerin capsules was assessed by ergometer stress testing in 12 patients with stable angina pectoris in a double-blind crossover study. In the morning the patients received transdermally applied nitroglycerin (TDS) which delivered 5.0 mg nitroglycerin in 24 hours together with a placebo capsule, respectively 1 nitroglycerin (NTR) capsule of 2.5 mg together with a plaster placebo. In the evening the first treatment group received 2 placebo capsules, and the second group 1 NTR capsule and 1 placebo capsule. Each period lasted 14 days. The patients performed a pre-medication ergometer stress test and repeated the test on the first and 14th day of each treatment period, 1 and 24 hours after medication. At the end of the second period all patients continued in an open study with TDS once a day for a further three months. Minor degrees of ST-segment depression, and in fewer patients, were observed at comparable workloads in the treatment tests compared with the pre-medication tests. The improvement after TDS on the first and last day of each period, 1 and 24 hours after medication, was significant and more marked than with NTR. The latter did not reach significance. Furthermore, increase of work capacity and elevation of angina threshold was greater with TDS than with NTR. Similar results were found at the end of the open study after 3 months' treatment with TDS. No development of tolerance was observed. PMID- 3099491 TI - Effects of mitomycin C in the central nervous system in newborn mice with special reference to neutral crest cells. PMID- 3099492 TI - Babesia bovis: vaccination trial with a dominant immunodiffusion antigen in splenectomised calves. AB - The dominant immunodiffusion antigen of Babesia bovis was prepared from the lysate of infected erythrocytes by cation exchange chromatography, gel filtration and preparative native acrylamide electrophoresis. It was seemingly free of other babesial antigens and tested as a vaccine. In vaccinated calves, compared to controls, there was a delay in parasitaemia and at times a statistically significant difference in parasite numbers. However, the vaccinates showed little difference in pathophysiological parameters or survival rates from the controls. It was concluded that serodominance cannot necessarily be correlated with protection. PMID- 3099493 TI - In vitro susceptibility of different mammalian lymphocytes to sporozoites of Theileria annulata. PMID- 3099494 TI - Migration of two Egyptian strains of Schistosoma mansoni in hamsters. PMID- 3099495 TI - [After years in nursing Mona has found "her home"]. PMID- 3099496 TI - [Promotion should entice nurses to long-term care]. PMID- 3099497 TI - Baculovirus transcription in the presence of inhibitors and in nonpermissive Drosophila cells. AB - Regulation of transcription within four well-defined regions of the DNA genome of the baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV) was studied in a permissive lepidopteran cell line. Spodoptera frugiperda IPLB-SF-21 and a nonpermissive dipteran cell line, Drosophila melanogaster DL-1. Cycloheximide, an inhibitor of protein synthesis, was used to identify immediate early transcripts and aphidicolin, an effective inhibitor of DNA replication, was used to distinguish early and late transcripts in S. frugiperda cells. Immediate early transcripts were identified in the HindIII-K (85 to 87.5%), the HindIII I/EcoRI-F (I/F from 35 to 37%) and the HindIII-P/EcoRI-P (p10 from 88.5 to 89.5%) regions of the genome. Late RNAs, defined by their sensitivity to aphidicolin as well as cycloheximide, overlapped the immediate early RNAs. Specific viral transcripts were synthesized in nonpermissive D. melanogaster cells infected with AcNPV but late viral transcripts were not observed. PMID- 3099499 TI - Immunomodifying activity of some amphiphilic compounds from pathogenic Pseudomonas aeruginosa strains. AB - Molecules of polysaccharide, lipopolysaccharide, and peptidoglycane from Pseudomonas aeruginosa were assayed as immunogens and immunomodifiers. The kinetics of humoral responses, phagocytic activity, splenic index variations, and immunomodulating ability of these molecules were studied. Their protective and immunomodifying effects were compared to those similarly produced by heat-killed bacteria suspensions. The influence of the nature and doses of these molecules as well as the intervals between their administration and the SRBC immunization were also studied. Results showed that higher IgM and IgG levels were produced by lower doses of lipopolysaccharide and peptidoglycane, respectively. Using these amphiphilic molecules at doses of 160 micrograms/mouse, a variable immunodepressive activity was observed. This dose-dependent effect which particularly altered the IgM synthesis, was also observed in phagocytic responses. The exopolysaccharide showed to be the most immunodepressive molecule, and this activity appeared to be dependent of dose and time of administration. PMID- 3099501 TI - [Methodology and application of defaunation in the growing ruminant]. PMID- 3099500 TI - Utilization of gluconate by Aspergillus niger. II. Enzymes of degradation pathways and main end products. AB - Aspergillus niger was grown from conidia on a medium with glucose as the source of carbon and potassium nitrate in non-limiting concentration as the source of nitrogen. After the exhaustion of glucose gluconate was added, this compound representing the almost only carbon source in the culture fluid at this time. Gluconate was used rapidly by the preformed mycelium, the main end-products of its metabolization being mycelial substance (including protein), CO2, and oxalate. In cell-free extracts from gluconate utilizing mycelia 8 enzymes of the Embden-Meyerhof (EM) pathway, 5 enzymes of the tricarboxylic acid (TCA) cycle, and an oxalate forming enzyme, oxaloacetate hydrolase (EC 3.7.1.1) were identified. The addition of fluoroacetate together with gluconate resulted in the accumulation of citrate, and in the inhibition of mycelial growth and of accumulation of oxalate. It is concluded that the EM pathway and the TCA cycle are involved in the formation of mycelial substance, CO2 and oxalate from gluconate. There is good correspondence between the rates of gluconate utilization and of oxalate accumulation which were observed immediately after the addition of gluconate and the in vitro activities of gluconokinase and oxaloacetate hydrolase, respectively, at this time. PMID- 3099498 TI - [Effect of drugs of the nootropic class on rat behavior after deprivation of the paradoxical stage of sleep]. AB - Pharmacological analysis was used for studying the influence of 24-hour deprivation of paradoxical sleep by Jouvet method on retention of conditioned reaction of passive avoidance in rats. Psychotropic substances of different action were used for the analysis: nootropes as anti-amnestic--pyracetam (400 mg/kg), kleregil (100 mg/kg), centrofenoxin (50 mg/kg) and watersoluble salt of 3 oxypiridin derivative (3-OP) (50 mg/kg) and tranquilizer of bensodiazepine series phenazepam (1 mg/kg) as antistress and antiphobic. It was established that 24 hour deprivation disturbed the elaborated reaction but did not change the rate of emotionality and orienting-investigating behaviour of rats in the open field. Nootropes effectively restored the conditioned passive avoidance reaction while phenazepam had no effect. This allows to suggest that Jouvet method of paradoxical sleep deprivation elicits amnesia and its cause is not only stress but deficit of paradoxical sleep. PMID- 3099502 TI - [Characterization of renal 25-hydroxycholecalciferol-1-hydroxylase in swine]. PMID- 3099503 TI - Effects of feeding ergot-contaminated grain to pregnant and nursing sows. PMID- 3099504 TI - [Orthopedic and microstructural studies of the hoof of fattening pigs in different types of stalls]. PMID- 3099505 TI - Chromatin behaviour in germinal vesicles of growing and fully grown pig oocytes. PMID- 3099506 TI - Effect of fasting on digestion of white clover leaflets by rumen microorganisms and possible implications in cattle bloat. PMID- 3099507 TI - Green coloration of superficial cervical lymph nodes in dogs tattooed in the ear. PMID- 3099508 TI - Study of some ionary parameters in horse serum and urine during halothane anaesthesia with xylazine premedication. PMID- 3099509 TI - Is the "environmental" component of the phenotypic variability in inbred mice influenced by the cytoplasm of the egg? PMID- 3099510 TI - [Morphological and functional aspects of placental maturing mechanisms in the cow. 1. Light microscopic findings]. PMID- 3099512 TI - Light-microscopic investigations on the retinae of dogs carrying the Merle factor. PMID- 3099511 TI - [Effect of long-lasting exertion of warm-blooded horses on membrane lipid synthesis in lymphocyte cultures]. PMID- 3099513 TI - Effect of dietary selenium on the prevention of exudative diathesis in chicks, with special reference to selenium transfer via eggs. PMID- 3099514 TI - Changes in circulating levels of iodothyronines, cortisol and endogenous thiocyanate in sheep during emotional stress caused by isolation of the animals from the flock. PMID- 3099515 TI - [Measurement of pharmacological and toxicological effects on the tracheal mucociliary clearance. Experiences with a new in vitro method]. PMID- 3099516 TI - Transperitoneal migration of spermatozoa in heifers. PMID- 3099517 TI - [Attenuation of the agent of avian infectious anemia (CAA) by serial passage in cell cultures]. PMID- 3099518 TI - [Development of a polyvalent erythrocyte diagnostic agent based on the antigens of Pseudomonas aeruginosa slime]. AB - The study has revealed the fundamental possibility, and established the concrete conditions of obtaining standard erythrocyte polyvalent diagnosticum for the detection of antibodies to the antigens of P. aeruginosa, belonging to 5 types most frequently occurring in clinical practice, in the passive hemagglutination test. The data on high type- and species-specificity of the new erythrocyte diagnosticum have been obtained, which indicates that slime antigens have been correctly chosen as sensitins and confirms the necessity of using the polyvalent preparation. Preliminary data on the clinical trial of the erythrocyte diagnosticum show the expediency of its use for the control of specific immune response in donors in the process of obtaining anti-P. aeruginosa hyperimmune plasma, as well as the possibility of using this method for the serological diagnosis of P. aeruginosa infection. The diagnostic preparation has been found to retain its activity for 10 months (the term of observation). PMID- 3099519 TI - [Epidemiological surveillance of meningococcal infection and the prediction of the development of an epidemic process]. AB - The signs necessary for the prognostication of the development of the epidemic process have been formulated on the basis of the epidemiological analysis of materials obtained in the process of trials of the system for the surveillance of meningococcal infection with the use of previously established characteristics. The data on the prevalence of meningococcal infection among different age groups and on the seasonal distribution of the infection as well as on the serogroups of meningococci isolated from patients, have been shown to be of importance for prognostication. PMID- 3099520 TI - [Current aspects of the short-term prognosis of meningococcal infection morbidity for the sake of epidemiological surveillance]. AB - The short-term prognosis of the epidemic situation requires the establishment of the system of constant surveillance, which takes into account the data on morbidity rates for several years, both total and in various age groups, the data on the morbidity level and its changes, induced by meningococci of the epidemic group, in the IV quarter of the year, the data on the level of carriership among the indicator groups of the population in this period, as well as the data on changes in antibody titers in the sera of donor blood samples taken in summer and in December. PMID- 3099521 TI - The effect of chronic alcohol ingestion on the contractile proteins of the rat heart. AB - With increasing duration of alcohol consumption the amounts of total myofibrillar proteins in CFY rats decreased slightly, but significantly (from 63.3 +/- 5.7 mg X g wet muscle weight to 54.9 +/- 5.9 mg X g-1 after 12 weeks on alcohol). Similar slight changes could be observed in the case of sarcoplasmic proteins. No significant changes were observed in the composition of the myofibrillar proteins. The densitiometrically calculated percentage ratios of myosin/actin, myosin light chains (LC1/LC2) and troponin components remained the same in the alcoholic animals. The same distribution of native myosin isoenzymes was found in the ventricles of the alcoholic animals as in the controls. We found no electrophoretically detectable evidence that a change in the composition of the myofibrillar proteins is responsible for the decreased contractility of the rat heart following chronic alcohol ingestion. PMID- 3099522 TI - Dye-ligand affinity chromatography of RNA polymerase II. AB - The binding of wheat germ RNA polymerase II to five different dye-ligand chromatography gels (Matrex gels, Amicon Corp.) was tested. A quantitative binding of the enzyme to four of the gels, namely Dyematrex gels Blue A, Blue B, Red A and Green A was observed. Only the Orange A gel column failed to bind the enzyme strongly. Nearly 100% of the activity could be recovered from the Green A column by elution with high salt concentration and high pH. Under these conditions only a part of the activity was eluted from the other three columns since the enzyme bound tightly. Enzyme activity could be removed from the columns by elution with nucleotide substrates, but the yield from the Blue A, Blue B and Red A columns was still low (7 to 42%). The Green A Matrex gel appeared to be useful for the purification and analysis of RNA polymerase. PMID- 3099523 TI - Enzymatic determination of isocitrate by amperometric monitoring of the rate of oxygen consumption. AB - A coupled enzymatic method elaborated for NAD+-dependent dehydrogenases has been adapted for NADP+-dependent isocitrate dehydrogenase, in combination with amperometric measurements. The isocitrate dehydrogenase activity dependent linearly on the isocitrate concentration in the range 0-2 X 10(-4) M. Application of this method affords a sensitive estimation of isocitrate even in turbid liquids such as fermentation broths. PMID- 3099524 TI - Metabolism of non-enzymic glycosylated low density lipoprotein by mini pig aortic endothelial cells. AB - [U-14C]-glucose was incorporated non-enzymatically into the protein moiety of human low density lipoprotein. The incorporation was time and glucose concentration dependent. Investigated mini pig aortic endothelial cells showed that the glycosylated low density lipoprotein was bound, internalized and degraded significantly less than that of the native one measured with [125-I]-low density lipoprotein. PMID- 3099525 TI - Investigation on the binding of tryptophan enantiomers to human serum albumin. AB - The binding of radiolabelled tryptophan enantiomers to human serum albumin was investigated by ultrafiltration and by the microparticle technique. L-Trp was found to exhibit a high degree of secondary binding. D-Trp showed increased degree of binding when the HSA concentration was decreased. Stereoselective binding has also been detected in stereoselectively labelled racemic mixtures. Both L- and D-Trp were found to compete for the primary binding site with specific benzodiazepine markers. All the experiments indicate that stereoselectivity of binding is much lower than generally believed. PMID- 3099526 TI - The role of the unit of mass in the allometric equation relating body size and metabolic rate. PMID- 3099527 TI - Investigation of hydration of macromolecules. III. Study of polyethylene glycol homologues by microwave measurements. AB - The microwave conductivity and permittivity of various homologues of polyethylene glycol (PEG), as well as those of dioxane, all dissolved in either water or electrolyte solutions containing 0.01 M MnSO4, were measured over the frequency range of 1.5 to 4.2 GHz, at a temperature of 30 degrees C. The conductivity was also determined at the frequency of 20 kHz, at the same temperature. We found that: The wavelength of the dielectric relaxation of water increased with the increase of the concentration of nonelectrolytes. The orientation polarization of PEG molecules with a degree of polymerization of n less than or equal to 12.5 can be detected over the microwave range studied. In solution of PEG macromolecules at a degree of polymerization n greater than 12.5 the microviscosity and the wavelength of dielectric relaxation of water significantly increase because of the cooperative action of regularly ordered hydrophilic groups. The ionic conductivity is inversely proportional to the microviscosity of the water. There is a constant conductivity over the microwave range studied, presumably due to the orientational polarization of water molecules interacting with the macromolecules (relaxation frequency f congruent to 0.25 to 0.5 GHz). The effect of PEG of a high polimerization degree on the structure of water is similar to the effect of a decreasing temperature. PMID- 3099528 TI - Cytochemical localization of adenylate cyclase activity in heart tissue with cerium. AB - Adenylate cyclase (AC) activity showed a doses depending inactivation of the basal activity and of the sodium fluoride stimulation by cerium in homogenates of unfixed and fixed guinea pig hearts. The isoproterenol and guanine nucleotide stimulation was not more than two times of the basal activity in glutaraldehyde prefixed heart homogenates in the presence of 2 mmol/l CeCl3. The inactivation of the AC (activity) by cerium was less than in the presence of lead. Test tube experiments showed no differences in the precipitation of imidodiphosphate in comparison with inorganic phosphate. The substrate AMP-PNP was not spontaneously hydrolysed by 2 mmol/l CeCl3. Ultrastructural analysis of cytochemical incubation of glutaraldehyde-fixed slices and small pieces of guinea pig heart tissue showed fine-amorphous precipitations of reaction products localized along the plasma membrane of the sarcolemma, the nexuses of the intercalated discs and the T tubule membranes. No precipitates were found neither on the junctional nor on other SR membranes. Nonspecific coarse and clumped precipitates have been detected in the intercellular space on components of the basal membranes. It was not able to demonstrate cytochemically stimulation of AC by hormones or by sodium fluoride. The localization of the basal AC activity in heart tissue seems to be better with cerium as capture agent than with lead. However, differences in the localization of the AC activity in heart tissue were not observed. PMID- 3099529 TI - Proctolin immunoreactive neurons in the human brain stem. AB - Using the peroxidase-antiperoxidase (PAP) technique it could be established that a variety of nerve cells of human Pons and Medulla oblongata contain proctolin like material. These neurons belong to the Nuc. olivaris caudalis, Nuc. originis n. hypoglossi, Nuc. raphes dorsalis and the Nuc. ambiguus. Furthermore, proctolin immunoreactive peptide was found to be contained in certain fiber systems (Lemniscus medialis and fiber tracts near the Raphe). PMID- 3099530 TI - Studies on internalization and intracellular localization of membrane DNA in mouse peritoneal macrophages, by means of lactoferrin-gold complex. AB - It is an experimental fact that lactoferrin binds to DNA. In the present study, a lactoferrin-gold complex was first bound by the cell surface, then became internalized (inside coated or smooth vesicles). Intracellularly the complex appeared in tube-like or vesicle-like structures, which approximated the nucleus, and some vesicles even showed indications of association with the external nuclear membrane. Neither membrane binding, nor internization of the lactoferrin gold complex had taken place in cells pretreated with DNase. PMID- 3099532 TI - Electron microscopical localization of non-specific cholinesterase activity in three principal parts of cat Pacinian corpuscles. AB - Non-specific cholinesterase (nCHE) activity was demonstrated histochemically on electron microscope level in 3 parts of Pacinian corpuscles from the cat mesenterium. The reaction product was abundant on the plasmic membrane of the inner core lamellae. Schwann cells of a myelinated portion of a sensory axon in Pacinian corpuscles were devoid of positive reaction to nCHE activity. These results are in agreement with those obtained in other sensory nerve endings. Therefore, the cells investing the terminal portion of an unmyelinated sensory axon are considered to be specialized Schwann cells. Furthermore, the amount of end product was lower on the specialized Schwann cells around ultraterminal than terminal portion of a sensory axon. A significantly higher nCHE activity confined to the inner core around the terminal portion of a sensory axon suggests the participation of this enzyme in the maintenance of ionic milieu in periaxonal microenvironment. PMID- 3099531 TI - [Intermediate filaments in cells of hyaline cartilage]. AB - After different fixation procedures great numbers of bundles of intermediate cytofilaments, 10 nm in thickness, could be detected in electron micrographs of chondrocytes from Processus xiphoideus of the rat, from the articular cartilage of the rabbit and from chondrocyte cultures from the articular cartilage of the rabbit. By means of the indirect immunofluorescence technique with monoclonal antibodies they could be clearly defined as vimentin. PMID- 3099533 TI - Light microscopical localization of acid and alkaline phosphatase activity by lanthanum-lead-(La-Pb)-methods. AB - This paper reports on the application of lanthanum cations instead of cerium ions as captures to detect acid and alkaline phosphatase activity in the rat kidney and small intestine. The basis of the proposed histochemical reactions is a three step procedure in analogy to the earlier published cerium-based techniques: the lanthanum phosphate was converted into lead phosphate and finally into the brown coloured lead sulfide [lanthanum-lead-(La-Pb)-reaction]. The results reveal that the La-Pb-reactions are more sensitive in comparison to the Ce-Pb-reactions. Methodological experiments involving lanthanide specific blocking reactions are discussed. Lanthanum cations are recommended as a useful tool in histochemical capture techniques of phosphatases. PMID- 3099534 TI - [Age dependent changes in the collagen content of the human oviduct]. AB - On the basis of present investigations, namely on account of the hydroxyproline determinations and the biomathematical analysis of data, the ageing of the human Fallopian tube with regard to its collagen content can be characterized as follows: Collagen concentration of the oviduct increases slightly and almost linearly up to the 5th decade of woman life. In the 2nd half of the fifth decade, i.e. already in the premenopausal years, this increase is accelerated, then changing into a yet almost linear but stronger rise of the collagen content. PMID- 3099535 TI - [Cell proliferation and glial fibrillary acidic protein in brain tumors]. AB - The results of histoautoradiographic and immunohistochemical studies of biopsy specimens of 15 brain tumours are reported. The specimens were labeled with 3H thymidine using an in vitro technique. Meningiomas, oligodendrogliomas and well differentiated astrocytomas showed a median S-phase fraction of about 1%. In contrast, the labeling indices of 4 from 7 anaplastic astrocytomas were higher (2.1, 3.0, 3.5, 11.4). With increasing degree of malignancy the proliferative heterogeneity of the tumours increases. In every glioma varying amounts of glial fibrillary acidic protein (GFAP) were detected immunohistochemically (PAP technique). In 3 high-grade gliomas (2 glioblastomas, 1 anaplastic astrocytoma) an inverse relation of the investigated parameters (high S-phase fraction, low GFAP expression) was found. An exact prediction on biological behaviour of an individual tumour by GFAP detection immunohistochemically is not possible, because a high GFAP content can be detected also in some malignant tumours. However, the 3H-thymidine labeling indices of viable parts of the tumours, probably reflecting the growth fraction seem to be clinically important parameters, especially in respect to the prognosis. PMID- 3099536 TI - [Thyroid reactions in Wistar rats during the circadian rhythm after ganglionectomy at normal temperature and under cold exposure with regard to the influence of the epiphysis cerebri]. AB - Serum thyroxin (T4), serum TSH, and pituitary TSH were measured by radioimmunoassay (RIA) and serum cholesterol by Liebermann-Burchard reaction in rats 4 times a day (light-dark cycle: 14 L: 10 D) after gangliectomy (bilateral extirpation of the Ganglia cervicalia superiora) at cold and normal temperature conditions. 80 male Wistar rats were divided into 4 groups: sham-operated group, 24 degrees C (297 K); sham-operated group, 10 degrees C (283 K); gangliectomy, 24 degrees C (297 K), and gangliectomy, 10 degrees C (283 K). We have sacrificed the rats 30 d after operations at the following day-times: middle light, middle darkness, 1 h after light "on" and 1 h after light "off" (they were exposed to cold 72 h before killing). It was found that gangliectomy significantly depressed blood level of thyroxin. On the other hand, it enhanced the serum cholesterol and TSH levels as well as the pituitary TSH content. Exposure to cold increased thyroxin, serum TSH and pituitary TSH. The cholesterol level, however, was significantly decreased. Gangliectomy causes a reduction of the cold-induced stimulation of thyroxin (significant), serum TSH, and pituitary TSH content (significant). The cholesterol (in relation to the cold-exposure alone) was significantly increased under these conditions. We have found similar results in another long-time experiment (90 d exposure) after gangliectomy as well as after pinealectomy. There also appears a lowered thyroxin and an increased cholesterol level (in dependency on the seasons). Gangliectomy induced a decrease of the pineal weight and a compensatory thyroid growth. Exposure to cold induced an increase of pituitary and pineal weights. Gangliectomy provokes a reduction of the cold-induced augmentation of the pineal weight. The results indicate that gangliectomy diminishes the total levels of circulating T4 in the presence of an intact pineal gland and reduces the cold-induced increase of T4 in long-time experiments (30 and 90 d post operationem). Both gangliectomy and cold condition led to an enhancement of serum TSH and pituitary TSH content. The exposure to cold was found to have a more severe influence. In the present study, we also have discussed the sympathetic denervation effect of the gangliectomy in relation to the thyroid and pineal gland. Due to certain contradictory data in the literature, we have also discussed the TRH-5-hydroxytryptamine (respectively melatonin) antagonism, though we were not able to determine whether peripheral and/or central mechanisms play the more important role in their regulation. PMID- 3099537 TI - [Model-free biomathematical analysis and description of correlations]. AB - Modelfree methods for nonparametric estimation of unknown continuous functions from measured values and their advantages as against fitting of analytical expressions are discussed. The main features are stated especially of the empirical regression and of the local adjusted polynomial approximation. These topics and problems of application of the procedures are illustrated by 3 examples coming from chronobiological, neuromorphometrical, and histochemical examinations. PMID- 3099538 TI - [Malignant otitis externa]. AB - Malignant external otitis is a progressive Pseudomonas infection starting in the external auditory canal. It tends to occur in the elderly diabetic patient and to invade cartilage, bone, nerves and adjacent soft tissues. Aggressive medical management and surgical debridement is curative in most cases as it appears in the case reported in the following communication. PMID- 3099539 TI - Expression of IgD on B cell malignancy. An immunopathological study of 50 cases. AB - Expression of IgD was studied immunopathologically on 50 cases of B cell lymphomas (B MLs), together with various B cell markers including IgM, kappa and lambda chains, B1, B2, (OK)B2, (OB)B7, (OK)T10, NUB1, Leu 1, Leu 14, and PCA. IgD was demonstrated on 19 cases heavily and on 8 weakly. It associated well with expression of two antigens, B2 (C3d receptor molecule) and Leu1 (pan-T antigen), besides IgM, while, B2 was closely related in expression on B MLs to (OK)B2, (OK)B7, and NUB1. lambda chain was dominant on IgD heavily-stained cases. Histopathologically, IgD positive MLs were distributed in various types. All of diffuse intermediate type were shown to be IgD positive (4/4, 3 heavily). As cases of this type were shown to express most of other B cell antigens present on non-tumorous primary follicle B cells or mantle zone B cells, this type of MLs is speculated to be a neoplastic counterpart of such non-tumorous B cells. Eight out of 18 cases of diffuse large cell type were IgD heavily positive, suggesting some unusual mechanisms in IgD expression on these neoplastic large cells, as non tumorous B cells lose most of their surface IgD soon after blastoid transformation. Other types of MLs were discussed with special emphasis on expression of IgD. PMID- 3099541 TI - IgM myeloma--its distinction from Waldenstrom's macroglobulinemia. AB - An autopsy case of multiple myeloma (MM) with marked elevation of serum IgM as an M-component, diagnosed as IgM myeloma, was described. Clinically, multiple bone lesions were found but neither lymphadenopathy, hepatosplenomegaly nor tumor mass formation in the gastrointestinal tract. Pathologically, the tumor cells proliferating in the bone lesions were mainly comprised of myeloma cells closely resembling mature plasma cells, though they contained immature cells as a minor cell population. At autopsy, slight infiltration of myeloma cells was confirmed in the lymph nodes, spleen and both kidneys, which is considered to be a terminal phenomenon that occurred in the clinical course of the case. From these findings, it appears reasonable that, though a monoclonal increase of serum IgM was found, this case differs from Waldenstrom's macroglobulinemia (WM) both clinically and pathologically and is rather situated within the category of MM. The occurrence of such a case is extremely rare, only 28 cases being reported in the literature, including 13 autopsy cases. The existence of IgM myeloma in the category of MM should be emphasized as a disorder distinct from WM. PMID- 3099540 TI - Mucormycosis in diabetic ketoacidosis. Role of unbound iron binding capacity of transferrin. AB - Increased susceptibility to Rhizopus oryzae in diabetes was investigated using mice in which diabetic ketoacidosis was experimentally induced. All of the diabetic mice which had developed ketoacidosis died within four days after inoculation of R. oryzae and their serum UIBCs (Unbound iron binding capacity) were significantly lower than those of the normal control mice. This study suggested that the decreased serum UIBC produced by diabetic ketoacidosis enhances the growth of R. oryzae in vivo. PMID- 3099542 TI - Vasomotor responses of isolated human coronary arteries to magnesium, nitroglycerin and verapamil: a comparison with coronary arteries from cat and rat. AB - The vasomotor responses in vitro to magnesium, nitroglycerin and verapamil were investigated in human coronary arteries. In order to examine possible species differences in reactivity to these agents, experiments were performed also on cat and rat coronary arteries. Potassium (124 mM) regularly produced stable contractions suitable for experiments with dilator agents. The order of potency for eliciting relaxation was the same in all three species; verapamil greater than nitroglycerin greater than magnesium. Maximum relaxation induced by nitroglycerin or magnesium was significantly lower in arteries from cat as compared to that obtained in coronary artery segments from man and rat. Spontaneous rhytmic activity was often present in human coronary arteries but never in arterial segments from cat or rat. The rhytmic activity was frequently enhanced by the addition of prostaglandin F2 alpha (3 microM) to the tissue bath, on the other hand the rhythmic activity was depressed, or even abolished, by potassium (124 mM), magnesium (1.2-13.2 mM), nitroglycerin (2.2 X 10(-5) M) or verapamil (10(-8)-10(-7) M). The magnitude of the vasomotor response of feline coronary arteries to nitroglycerin or verapamil was dependent on the extracellular concentration of magnesium; in the presence of a high concentration of magnesium (4.4 mM) the dilator effect of nitroglycerin was enhanced while that of verapamil was slightly depressed. The dilator activity of the two agents was not changed by incubation of the vessel segments in a magnesium-free medium as compared to that obtained in the standard (1.2 mM Mg) buffer solution. PMID- 3099543 TI - Phthalate esters: effects of orally administered dibutylphthalate on cytochrome P 450 mediated metabolism in rat liver and lung. AB - Dibutylphthalate (DBP) was administered to male Sprague Dawley rats in oral doses of 0.01, 0.1 and 1.0 mmol/kg for five days. The lower dose was considered relevant to human intake. Additional groups were given a recovery period of four weeks without DBP. DBP significantly increased the liver microsomal concentration of cytochrome P-450 (48%) at the lowest dose and NADPH-cytochrome-c-reductase activity (28-29%), at the two lower doses. The liver microsomal metabolism of n hexane increased to about the same extent at all dosage levels. The main increase was found in the formation of the preneurotoxic metabolite 2-hexanol. The induction of cytochrome P-450 and NADPH-cytochrome-c-reductase in liver microsomes did not return to normal after the period of recovery, whereas the metabolism of n-hexane normalized during the same period of time, indicating that the majority of the induced forms of cytochrome P-450 were not related to n hexane metabolism. No major changes were observed in the liver microsomal metabolism of B(a)P. The only effect found in cytochrome P-450 related metabolism in lung microsomes was a decrease of the B(a)P metabolism, especially in the formation of the 9,10- and 4,5-diol metabolites at lower dosage levels. It is suggested that DBP and its hydrolyzed products formed in the intestine after oral administration exert the same effect on some specific forms of cytochrome P-450 in liver and lung. It is concluded that DBP is a moderate to weak inducer of several minor forms of liver microsomal cytochrome P-450 enzymes in doses which may be relevant to human oral intake. PMID- 3099544 TI - Acute phase reactants in the initial phase of giant cell arteritis. AB - The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen and haptoglobin were followed weekly during the initial phase of corticosteroid treatment in 18 patients with 19 episodes of giant cell arteritis (GCA). Fibrinogen and CRP decreased most rapidly, with normal values in 67% of the patients after two weeks of treatment. After two weeks 56% of the patients had normal ESR values and 76% after five weeks. Haptoglobin normalised most slowly, no patient having a normal value after one week, 29% after two weeks and 75% after six weeks. For routine clinical use, we found the ESR alone sufficient for monitoring the initial steroid treatment. PMID- 3099545 TI - Waldenstrom's macroglobulinemia in monozygotic twins. AB - This paper reports a unique familial occurrence of Waldenstrom's macroglobulinemia (WM) in monozygotic twins. The determination of twin monozygosity has been performed by electrophoretic and immunological typing of genetic systems (erythrocyte blood groups, leucocyte antigens and serum protein polymorphism). The two monoclonal IgM differ one from the other by their light chain type and their idiotypic determinants. Although a genetic predisposition to WM exists in these twins, the gene recombination leading to idiotypic specificity and light chain assortment occurs independently of the monoclonal malignant involvement. PMID- 3099546 TI - Relation between the contact time and venous and alveolar PCO2 at rest. PMID- 3099547 TI - The influence of moderate hypothermia on cerebral cortex tissue oxygen tension. AB - The validity of mechanisms balancing oxygen transport and consumption in hypothermia are difficult to analyse because almost any parameter of the transport system is temperature dependent. Two types of experiments have been performed in the rat cerebral cortex to elucidate this problem: PO2 microelectrode study: 32-37 degrees C body temperature, spontaneous respiration. Measurements within the upper tissue layer of 200-500/microgram thickness (N = 15). PO2 surface electrode study: 26-37 degrees C body temperature, artificial respiration. Investigation of the arachnoidal and pial area (N = 46). Mean tissue PO2 (+/- SD) of neo- and archeocortex declined slightly from 27.8 +/- 14.4 mm Hg at 37 degrees C to 25.5 +/- 15.5 mm Hg at 32 degrees C (p less than 0.05, n = 15). Surface PO2 (sPO2) (+/- SD) in response to hypothermia showed a small decrease from 18.1 +/- 4.5 mm Hg (n = 186) at 37 degrees C to 14.7 +/- 4.3 mm Hg (n = 41) at 26 degrees C (p less than 0.05, N = 46). Despite different initial PO2 values at normothermia both groups of experiments are characterized by the same relatively small hypothermia induced PO2 decrease. Oxygen transport and consumption might be balanced under hypothermia and tissue hypoxia does not exist in the temperature range between 26 degrees and 37 degrees C. PMID- 3099548 TI - A role of prostaglandin I2 in hypoxia-induced increase in coronary flow in the perfused rat heart. PMID- 3099549 TI - In line monitoring of carbon dioxide via a gas permeable window. PMID- 3099550 TI - Genetic high density lipoprotein deficiency states and atherosclerosis. PMID- 3099551 TI - Apoprotein A-I and lecithin: cholesterol acyltransferase in a patient with Tangier disease. PMID- 3099552 TI - Clinical syndrome and lipid metabolism in hereditary deficiency of apolipoproteins A-I and C-III, variant 1. PMID- 3099553 TI - Cholesterol efflux: mechanism and regulation. PMID- 3099554 TI - Mucopolysaccharidoses. AB - The MPSs are a heterogeneous group of disorders caused by the deficiency of one of ten lysosomal enzymes and the resultant accumulation of glycosaminoglycans in tissues and organs. The phenotypic variations of each disorder are continuing to be expanded, while the biochemical explanation of these variations needs to be defined. Mucopolysaccharidoses should not be diagnosed solely on clinical grounds, since laboratory confirmation by specific enzyme assay in now available. Prenatal diagnosis is possible for MPSs by amniocentesis. Chorionic villus sampling offers the possibility of first trimester diagnosis. Carrier detection in Hunter's syndrome is not routinely performed, but new procedures may make this needed service more available. No definitive treatment is available. Bone marrow transplantation appears to improve the somatic disease, but correction of the central nervous system disorder may not be possible. The successful development of gene-therapy may in the future provide a means of treatment in MPSs. The management of MPSs can be improved by a better understanding of the natural history of the somatic and central nervous system deterioration in the different disorders. Systematic evaluation and appropriate treatment can lead to an improved quality of life. PMID- 3099555 TI - Platelet activating factor and asthma. PMID- 3099557 TI - The effect of anti-rheumatic drugs on factors from porcine synovium inducing chondrocyte mediated cartilage degradation. AB - A selection of NSAID's and diphosphonates were studied in a tissue culture model of cartilage degradation utilising porcine synovium and bovine nasal cartilage. All the NSAID's significantly reduced cartilage degradation when incorporated into the synovial culture medium. Lesser reductions were recorded when preformed chondrocyte stimulating factors were used and NSAID's added at the cartilage assay stage. These findings suggested that the principle site of action of NSAID's is upon the production of chondrocyte stimulating factors. None of the NSAID's tested affected inherent cartilage degradation. Diphosphonates had the opposite effects, they increased inherent cartilage degradation but had no effect on chondrocyte mediated cartilage degradation. The relationship of these results to previous known effects of NSAID's and diphosphonates upon cartilage is discussed. In addition, correlations between chondrocyte stimulating factors, catabolin and interleukin 1 are made. PMID- 3099556 TI - Unique properties of auranofin as a potential anti-rheumatic drug. AB - Gold salts, auranofin (AF), aurothiomalate (ATM) and aurothioglucose (ATG) displayed immunosuppressive action in a series of in vitro assays which mimic the cell-cell interactions thought to occur in rheumatoid arthritis. The gold salts inhibited phytohaemagglutinin (PHA)-induced thymidine incorporation and gamma-IF production by peripheral blood mononuclear cells, as well as IL-2-induced proliferation of PHA-blasts. The separate addition of IL-2 and gamma-IF partly reversed the anti-proliferative effects of ATM and ATG; however, the addition of IL-1 had no effect. ATM and ATG inhibited PHA-stimulated IL-1 production by mononuclear cells but not spontaneous or LPS-induced IL-1 production by adherent monocytes. It was concluded that ATM and ATG inhibited lymphocyte function and lymphocyte-amplification of macrophage function. The anti-proliferative effects of AF were partly reversed by IL-2 but not by gamma-IF or IL-1. AF inhibited PHA stimulated IL-1 production by mononuclear cells as well as spontaneous and LPS induced production by adherent cells. It appeared that AF inhibited lymphocyte and macrophage function directly. AF also displayed potential anti-inflammatory activity in that it inhibited PGE2 and collagenase production by proteolytically dispersed rheumatoid synovial cells. PMID- 3099558 TI - Vitamin E and vitamin C inhibit arachidonate-induced aggregation of human peripheral blood leukocytes in vitro. AB - Arachidonate induces aggregation of human polymorphonuclear (PMN) and mononuclear (MNL) blood leukocytes. This is mediated by the lipoxygenase pathway, as it is prevented by lipoxygenase inhibitors and can also be induced by leukotriene B4 (LTB4). Vitamin E and vitamin C have profound effects on the functional state of leukocytes, some of which may involve the lipoxygenase pathway. This study shows that both vitamins inhibit arachidonate-induced aggregation of PMN and MNL, in a concentration-dependent way. BW-755, previously shown to inhibit arachidonate induced PMN and NML aggregation, was found to potentiate the inhibitory activity of both vitamins. When LTB4 was used as an aggregating agent, vitamin E markedly inhibited PMN and MNL aggregation, whereas vitamin C was ineffective. The prevention of PMN and MNL aggregation by vitamin E might account, at least partially, for the reported beneficial effects of vitamin E supplementation in some experimental syndromes characterized by leukocyte activation. PMID- 3099559 TI - Immunosuppressive actions of prostaglandins and the possible increase in chronic inflammation after cyclo-oxygenase inhibitors. AB - A method is described to examine the activity of potential antirheumatic drugs on the release and activity of lymphokines and interleukins in vitro, using human peripheral blood mononuclear cells and synovial cells. The enhancement of lymphocyte-mediated effects brought about by non-steroid anti-inflammatory drugs has been shown to be the result of inhibition of a prostaglandin negative feedback mechanism. Since the underlying features of rheumatoid arthritis and related diseases are almost certainly brought about by mononuclear cell activation, their enhancement by non-steroid anti-inflammatory drugs might well have serious clinical implications. The possibility is discussed that aspirin like drugs, administered in large doses to patients suffering slight joint pain, might well exacerbate, perpetuate or even initiate a chronic arthritic condition. We suggest that, as soon as the disease has been diagnosed, patients should be treated with a disease-modifying drug and, if necessary, an analgesic which does not inhibit cyclo-oxygenase. PMID- 3099561 TI - Transient giant inverted T waves during flecainide intoxication. PMID- 3099560 TI - Newer antiarrhythmic drugs in children. AB - Our experience with the use of five new antiarrhythmic drugs for treating life threatening arrhythmias in children will be briefly reviewed. Prevention of recurrent episodes of atrial flutter with digoxin and local anesthetic antiarrhythmic drugs often is only moderately successful, benefiting 65% of patients. Amiodarone is particularly useful for those patients who cannot be controlled on this regimen. We caution that the heart rate be monitored carefully when therapy with amiodarone is initiated in patients likely to have sick sinus syndrome. We have found mexiletine useful for controlling significant ventricular arrhythmias in patients with congenital heart disease. Likewise, 79% (11 of 14) of patients with ventricular tachycardia treated with amiodarone were well controlled. However, the range of disease categories (congenital heart disease, myocarditis, cardiomyopathy) in which amiodarone is effective is much broader than for mexiletine. Although other investigators have used amiodarone successfully for controlling supraventricular tachycardia in the Wolff-Parkinson White syndrome or secondary to concealed accessory AV connections, we recommend surgical ablation. Propafenone has significantly improved our ability to control postoperative JET. Although JET is self-limited in duration and spontaneously remits, it frequently produces life-threatening hemodynamic compromise in the postoperative setting. Propafenone slows the ventricular rate into a range in which AV sequential pacing may be instituted. Generally, after 24 to 72 hours, the patient may be quickly weaned from propafenone. Chronic incessant supraventricular tachycardia (SVT) is frequently associated with a dilated cardiomyopathy. The two most common mechanisms of incessant SVT are PJRT and AET. We have found encainide and ethmozine extremely effective in suppressing tachycardia episodes in PJRT and AET, respectively. Medical therapy has been associated with few side effects. PMID- 3099562 TI - Effects of flecainide on the cellular electrophysiology of neonatal and adult cardiac fibers. AB - The acute cellular electrophysiologic actions of flecainide acetate on isolated neonatal and adult canine ventricular myocardium and Purkinje fibers were evaluated with standard microelectrode techniques. Flecainide, 0.1 to 10.0 micrograms/ml, produced concentration-dependent decreases in action potential amplitude, overshoot, and phase O Vmax of adult ventricular myocardium and Purkinje fibers. The greatest effects were on Vmax. Neonatal action potential characteristics were affected to a lesser degree by flecainide. Flecainide had disparate effects on myocardial and Purkinje fiber repolarization and refractoriness. In adult ventricular myocardium, action potential duration (APD) and effective refractory period (ERP) increased progressively with drug concentration. APD and ERP were increased to a lesser degree in neonatal myocardium. In adult Purkinje fibers, APD decreased progressively with increasing flecainide concentrations. ERP decreased at 0.1 and 1.0 microgram/ml, but returned to control values at 10.0 micrograms/ml. APD and ERP of neonatal Purkinje fibers responded to a lesser degree. At faster stimulation frequencies (2 to 4 Hz), flecainide produced significant frequency-dependent decreases in Vmax in adult Purkinje fibers. Such use-dependency was not evident in neonatal fibers. These data indicate a significantly lower sensitivity of immature cardiac tissues to the electrophysiologic effects of flecainide. PMID- 3099563 TI - Capsules for transplanted islet cells. PMID- 3099564 TI - A double-blind randomized study comparing different dose regimens of H2-receptor antagonists on 24-hour gastric secretion in normal subjects and duodenal ulcer patients. AB - Duodenal ulcer therapy with H2 antagonists initially aimed to control acid secretion throughout the 24-h period, but recently nighttime suppression has been advocated. The effect of single nighttime regimens of cimetidine 400 mg BID, cimetidine 800 mg HS, ranitidine 150 mg HS, and placebo on 24-h intragastric acidity, nocturnal acid output, and pepsin secretion were studied in four healthy volunteers and four patients with healed duodenal ulcer. A nonrandomized dose of cimetidine 1200 mg HS was also studied. For all four treatments, daytime (0730 2230 h) intragastric acidity was reduced by 4-30% in the normals and by 10-44% in the duodenal ulcer patients (NS), while 24-h intragastric acidity was reduced by 44-46% and 40-64%, respectively (p less than 0.05). Reduction in nocturnal acid output was 82-96% in normals and 91-99% in duodenal ulcer, respectively. Pepsin concentration was unaffected by treatment but pepsin concentration was significantly (p less than 0.05) lower in patients than in normals. Mean 24-h gastric acid secretion was reduced by a single nighttime treatment with an H2 receptor antagonist, while nocturnal acid secretion was virtually abolished. H2 antagonists given only at night deserve further clinical evaluation to determine the minimal effective dose and optimal duration of suppression to achieve ulcer healing. PMID- 3099566 TI - Avoiding medication errors with transdermal nitroglycerin products. PMID- 3099565 TI - Normal pregnancy in a patient with a postpartum factor VIII inhibitor. AB - A patient who had developed a VIII:C IgG-Kappa antibody after her first delivery became pregnant for a second time. At that time the titer of the inhibitor had increased fourfold, remaining at high levels throughout the rest of the pregnancy. The neonate exhibited an inhibitor with characteristics identical to that of the mother which could not be detected 3 months after birth. No hemorrhagic complications in either of the subjects were observed. PMID- 3099568 TI - Diabetic ketoacidosis presenting with a normal anion gap. PMID- 3099567 TI - Primary sclerosing cholangitis in the presence of a lupus anticoagulant. AB - Lupus anticoagulant, an immunoglobulin that prolongs the partial thromboplastin time, has been associated with thrombotic events, including deep venous thrombosis, pulmonary emboli, and Budd-Chiari syndrome. In this report, primary sclerosing cholangitis was diagnosed in a man with a 10-year history of multiple thrombotic events related to a circulating lupus anticoagulant. Progressive jaundice and pruritus developed, and sclerosing cholangitis was confirmed by direct cholangiography. Sclerosing cholangitis is the second hepatobiliary disease reported in association with a lupus anticoagulant. PMID- 3099569 TI - Is carbaryl as safe as its reputation? PMID- 3099570 TI - Anion gap-bicarbonate relation in diabetic ketoacidosis. AB - The relation between the serum anion gap and the serum total carbon dioxide concentration was studied in 100 admissions of patients with diabetic ketoacidosis and 43 normal control subjects. In 20 admissions of patients with diabetic ketoacidosis (Group 1), the patients had no other conditions or medications known to alter acid-base or electrolyte homeostasis, whereas in 80 admissions of patients with diabetic ketoacidosis (Group 2), the patients had at least one of these factors. Analysis of the change in total carbon dioxide compared with the change in anion gap in Group 1 and control subjects revealed the following relation: change in total carbon dioxide = 0.74 + 1.00 X change in anion gap, in meq/liter (r = 0.886, p less than 10(-7]. The 95 percent prediction interval for detecting mixed acid-base disorders with this equation was +/- 8 meq/liter. Analysis of all admissions of patients with diabetic ketoacidosis and control subjects combined showed that the anion gap increased 0.24 meq/liter per mg/dl increase in blood urea nitrogen (with total carbon dioxide constant). Because the highest blood urea nitrogen level in Group 1 and control subjects was 22 mg/dl, the change in total carbon dioxide-change in anion gap regression is generally not valid for blood urea nitrogen levels higher than 22 mg/dl. Thus, both the wide prediction interval and volume depletion (as reflected by blood urea nitrogen level) impair the usefulness of the anion gap as a screen for mixed acid-base disorders in patients with diabetic ketoacidosis. PMID- 3099571 TI - Enhancement of granulopoiesis by lithium carbonate in a patient with hairy cell leukemia. AB - A 73-year-old patient with hairy cell leukemia and profound granulocytopenia both before and after splenectomy was treated with lithium carbonate. With serum lithium level maintained in the therapeutic range, granulocyte count steadily increased from a level below 200/mm3 to 800/mm3 over a two-week period. This trend reversed upon withdrawal of lithium. A second hematologic response occurred when the drug was reintroduced. The data support the contention that lithium carbonate may effectively stimulate granulopoiesis on a long-term basis, and this pharmacologic approach may be a useful adjunct to the management of hairy cell leukemia. PMID- 3099572 TI - The effect of IFN-gamma and alpha on Con-A stimulated T-cell proliferation: role of monocytes. AB - Interferon gamma (IFN-gamma) and alpha (IFN-alpha) have been shown to influence T cell proliferation in several systems. Since both species of IFN affect monocyte (Mo) functions, it is conceivable that these effects are mediated through Mo. In the present study, the effect of IFN-gamma and alpha on concanavalin A (Con A) driven T-cell proliferation was investigated under suboptimal culture conditions. T-cell proliferation was augmented by IFN-gamma. The stimulatory effect of IFN gamma was Mo mediated and required the pretreatment of Mo with IFN-gamma prior to co-culture with T-cells. Addition of IFN-gamma during co-culture or pretreatment of T-cells with IFN-gamma was ineffective in achieving augmentation. IFN-gamma induced enhanced T-cell proliferation was not due to increased interleukin-I (IL I) production by Mo pretreated with IFN-gamma, because addition of IL-I to control Mo-T-cells co-culture failed to increase T-cell proliferation. In contrast, IFN-alpha suppressed T-cell proliferation. The inhibitory effect of IFN alpha was not mediated through Mo and could be achieved by preincubating the T cells with IFN-alpha. These results demonstrate opposing effects of the two species of IFN on Con A-driven T-cell proliferation. In addition, Mo play an obligatory role in IFN-gamma induced stimulation, whereas Mo-IFN-alpha interaction is not required for IFN-alpha mediated suppression of T-cell proliferation. PMID- 3099573 TI - Acute myelocytic leukemia in a patient treated with hexamethylmelamine. AB - This case report describes a 76-year-old white woman who was found to have ovarian cancer and underwent chemotherapy with hexamethylmelamine. After 34 months of therapy, she developed an acute myelocytic leukemia. Although commonly reported as a side effect of alkylating agents, this is believed to be the first reported case of an acute nonlymphocytic leukemia associated with hexamethylmelamine use. PMID- 3099574 TI - Isolated and syndromic cryptophthalmos. AB - The association between cryptophthalmos and multiple congenital malformations has been well documented over the last century. Numerous authors have described cases as the cryptophthalmos syndrome, but recently reports of cases without cryptophthalmos have led several authors to use the eponymic designation Fraser syndrome. We have seen seven cases of cryptophthalmos syndrome, including three sib pairs. All presented with cryptophthalmos and bilateral renal agenesis in addition to other characteristic associated malformations. A literature review showed 124 cases in which 27 demonstrated isolated cryptophthalmos, while 97 showed a pattern of multiple congenital malformations. We selected four major and eight minor criteria which enabled us to classify 86 of those cases as having cryptophthalmos syndrome with 11 remaining unclassified. Cryptophthalmos demonstrates equal sex distribution, occurrence in sibs, consanguinity in families with more than one affected child, and lack of vertical transmission- strongly suggesting autosomal recessive inheritance. Isolated cryptophthalmos or cryptophthalmos sequence was sporadic in 16 cases and familial in 11. The familial cases occurred in three families and demonstrated vertical transmission. The pathogenesis of this syndrome is unknown. There are similarities to animal models of maternal vitamin A deprivation and defects in programmed cell death. Cryptophthalmos syndrome should be considered in the differential diagnosis of cases with multiple congenital malformations, especially when they are associated with renal agenesis, even in the absence of cryptophthalmos. PMID- 3099575 TI - Do total nutritional admixtures benefit your patients? PMID- 3099576 TI - Fetal blood group determination in first-trimester pregnancy for the management of severe immunization. AB - The presence or absence of Rho (D) and Kell antigens on fetal red blood cells was determined in the first trimester of pregnancy on erythrocytes obtained by chorionic villi sampling with the use of mixed agglutination and solid phase microimmunofluorescence techniques. Pregnancies in one Kell-sensitized woman and seven severely RH-sensitized women with a poor obstetric history and a partner heterozygous for the offending antigen were examined. A conclusive diagnosis could be made in seven of the eight cases studied. PMID- 3099577 TI - Routine hepatitis screening in adolescent pregnancies: is it cost effective? AB - In most obstetric centers routine serum screening for hepatitis B is not part of standard prenatal care. This study was designed to determine whether hepatitis B screening is cost effective for routine prenatal testing. In a prenatal population of 585 adolescents the cost-benefit ratio of hepatitis B screening was compared with that of routine syphilis screening. Eight positive results were detected, with a cost of $1755 per positive case. This compared favorably with the frequency and cost of detection of syphilis in the same population. Routine hepatitis B screening is recommended for consideration in similar prenatal populations. PMID- 3099578 TI - Academia--an endangered species. PMID- 3099579 TI - Bacillus cereus panophthalmitis manifesting as an orbital cellulitis. PMID- 3099580 TI - Grand mal seizure during argon laser panretinal photocoagulation. PMID- 3099581 TI - Bacteria associated with obstructive pulmonary disease elaborate extracellular products that stimulate mucin secretion by explants of guinea pig airways. AB - Certain cell-free filtrates from broth cultures of Pseudomonas aeruginosa, Hemophilus influenzae and Streptococcus pneumoniae stimulate secretion of glycoconjugates by explants of guinea pig trachea. The stimulatory effect is not related to toxicity or damage to the respiratory mucosa, as well as could be determined by ultrastructural examination of the explants after exposure. Bacteria isolated from patients with a history of chronic obstructive lung disease (P aeruginosa from cystic fibrosis, H influenzae, and S pneumoniae from chronic bronchitis) do not demonstrate increased frequency of positive strains or greater stimulation of secretion than organisms isolated from other individuals. At least three stimulatory substances are found in cell-free filtrates of P aeruginosa. They appear to be proteins of molecular weight 60,000-100,000 as determined by gel filtration. Within the crude filtrate, they are relatively stable to heat, proteolysis, and storage at 4 C and in liquid nitrogen. The stimulatory activity is not lost upon subculture of the bacteria. When isolated from the filtrate by column chromatography, they become labile to heat and trypsin. Isolated active fractions show proteolytic activity coinciding with mucin-stimulating capacity, suggesting a relationship with Pseudomonas proteases. Stimulatory substances released by S pneumoniae and H influenzae appear to be different from those elaborated by Pseudomonas. They are extremely labile to heat and storage, and the capacity to stimulate secretion is lost on subculture. Preliminary gel filtration indicates the S pneumoniae stimulatory substance(s) is in a molecular weight range of 100,000-300,000 daltons, while that of H influenzae is between 50,000 and 200,000. The results suggest bacteria which chronically infect or colonize respiratory airways of individuals suffering from obstructive lung disease can elaborate extracellular product(s) capable of stimulating secretion of mucin. Thus, the bacteria themselves may contribute to local manifestations and, ultimately, to the pathogenesis of obstructive disease. PMID- 3099582 TI - Dental metric assessment of the omo fossils: implications for the phylogenetic position of Australopithecus africanus. AB - The discovery of Australopithecus afarensis has led to new interpretations of hominid phylogeny, some of which reject A. africanus as an ancestor of Homo. Analysis of buccolingual tooth crown dimensions in australopithecines and Homo species by Johanson and White (Science 202:321-330, 1979) revealed that the South African gracile australopithecines are intermediate in size between Laetoli/hadar hominids and South African robust hominids. Homo, on the other hand, displays dimensions similar to those of A. afarensis and smaller than those of other australopithecines. These authors conclude, therefore, that A. africanus is derived in the direction of A. robustus and is not an ancestor of the Homo clade. However, there is a considerable time gap (ca. 800,000 years) between the Laetoli/Hadar specimens and the earliest Homo specimens; "gracile" hominids from Omo fit into this chronological gap and are from the same geographic area. Because the early specimens at Omo have been designated A. afarensis and the later specimens classified as Homo habilis, Omo offers a unique opportunity to test hypotheses concerning hominid evolution, especially regarding the phylogenetic status of A. africanus. Comparisons of mean cheek teeth breadths disclosed the significant (P less than or equal to 0.05) differences between the Omo sample and the Laetoli/Hadar fossils (P4, M2, and M3), the Homo fossils (P3, P4, M1, M2, and M1), and A. africanus (M3). Of the several possible interpretations of these data, it appears that the high degree of similarity between the Omo sample and the South African gracile australopithecine material warrants considering the two as geographical variants of A. africanus. The geographic, chronologic, and metric attributes of the Omo sample argue for its lineal affinity with A. afarensis and Homo. In conclusion, a consideration of hominid postcanine dental metrics provides no basis for removing A. africanus from the ancestry of the Homo lineage. PMID- 3099583 TI - Morphometrics of the anterior dentition in strepsirhine primates. AB - Size variations in the anterior dentition were analyzed for 26 species of strepsirhine primates. The upper and lower incisor rows of strepsirhines, like those of anthropoid primates, scale isometrically with body size. Within the order Primates, strepsirhines exhibit the smallest incisors relative to body size, followed in increasing size by tarsiers, platyrrhines, and catarrhines. If the lateral teeth of the indriid toothcomb are interpreted as incisors and not canines, correlations between mandibular tooth size variables and body weight are maximized. The upper incisors of strepsirhines are extremely small and frequently widely separated, most likely to minimize occlusion with the toothcomb. Species deviations for assorted size variables of the anterior dentition generally fail to reflect functional variations in the use of the anterior teeth; some of the variables, however, do reflect taxonomic differences within the Strepsirhini. Although toothcomb size variations among extant strepsirhines are more readily interpreted in terms of gum feeding and bark scraping than they are in terms of grooming, anterior dental morphology as a whole is more easily explained by a grooming hypothesis when existing models of toothcomb origins are considered. PMID- 3099585 TI - Television and health education: stay tuned. PMID- 3099584 TI - Gene frequencies and admixture estimates in a Mexico City population. AB - Five hundred and ten students of the Universidad Nacional Autonoma de Mexico were tested to determine the distribution of ABO, MN, Rr-Hr blood groups, and serum haptoglobin, albumin, and Factor Bf types. Based on the results we found that the proportion of Indian and White genes are of 56.16 and 43.84%, respectively in the dihybrid model and 2.93, 56.22, and 40.85% for Blacks, Indians, and Whites in the trihybrid one. The present study reveals a higher proportion of Indian genes in the Mexico City population than estimated in previous publications. Reasons why the present results apply to a much larger group of Mexico City mestizos than the previous ones are given. PMID- 3099586 TI - The cost-effectiveness of three smoking cessation programs. AB - This study analyzed the cost-effectiveness and distribution of costs by program stage of three smoking cessation programs: a smoking cessation class; an incentive-based quit smoking contest; and a self-help quit smoking kit. The self help program had the lowest total cost, lowest per cent quit rate, lowest time requirement for participants, and was the most cost-effective. The most effective program, the smoking cessation class, required the most time from participants, had the highest total cost, and was the least cost-effective. The smoking contest was in-between the other two programs in total costs, per cent quit rate, and cost-effectiveness; it required the same time commitment from participants as the self-help program. These findings are interpreted within the context of community based intervention in which the argument is made that cost-effectiveness is only one of several factors that should determine the selection of smoking cessation programs. PMID- 3099587 TI - Treatment of ankle sprains in young athletes. AB - To study the incidence of fibulocollateral ligament ankle sprains in the young male athlete, a survey of 84 varsity basketball players was done. Seventy percent of the players had a history of an ankle sprain. Eighty percent of those with a positive history had multiple sprains. Most of the injuries were mild, but in 32% of the injuries, the athlete missed more than 2 weeks of play. No medical attention was sought in 55% of the cases. About 50% of the athletes with a sprain had residual symptoms from their injuries; 15% of the injured athletes felt that their residual symptoms compromised their playing performance. This article emphasizes the potential seriousness of the ankle sprain in the young athlete and presents a recommended method of management, including assessment of severity, treatment, and rehabilitation. PMID- 3099589 TI - Intralabyrinthine osteogenesis in Cogan's syndrome. AB - Temporal bones from a 64-year-old man who had Cogan's syndrome were examined by light microscopy. Although tissues of the middle ear appeared unremarkable, extensive ectopic bone formation was observed bilaterally in the inner ear membranous labyrinth. Such osteogenesis completely obliterated the cochlear compartments apically. Only the scala tympani compartment of the basal cochlear turn remained patent. Ectopic bone tissue was observed also in the vestibular semicircular canals. Marked degeneration of eighth nerve fibers and associated ganglion cells also was observed. To our knowledge, this report represents only the fourth temporal bone findings of Cogan's syndrome and demonstrates a more advanced pathologic state of inner ear pathology than those reported previously. PMID- 3099591 TI - Factor VIII concentrate-responsive thrombocytopenia, hemolytic anemia, and nephropathy. Evidence that factor VIII:von Willebrand factor is involved in its pathogenesis. AB - A 4-year-old Japanese girl had a congenital disorder that was characterized by recurrent thrombocytopenia, hemolytic anemia, hematuria, and proteinuria, which were repeatedly improved by the infusion of factor VIII concentrate. She developed the similar symptoms within 1 h after 1-desamino-8-D-arginine vasopressin (DDAVP) administration. Coagulation studies 30 and 60 min after DDAVP infusion showed a disappearance of large factor VIII:von Willebrand factor (VIII:vWF) multimers, which was the same abnormality that was observed at acute episodes. There were no significant changes in the plasma levels of 6-keto prostaglandin F1 alpha and thromboxane B2 before and after DDAVP infusion. These results provide further support that VIII:vWF is directly involved in the pathogenesis of this congenital disorder. PMID- 3099590 TI - The role of the central monoaminergic system and rapid eye movement sleep in development. AB - Transmission of information in the brain is of a chemical nature. Neurotransmitters are present at very early stages of brain development, having trophic effects on maturation of target neurons as well as mediating the behavioral repertoire of the immature brain. Many centrally acting psychoactive drugs which are commonly used (also during pregnancy) for treatment of depression, asthma, hypertension, epilepsy, parkinsonism, hyperkinetism and other neurological and psychiatric disorders act directly on brain neurotransmitters (in particular monoamines) and behavioral states. Disturbances observed later in life in animals and man, as a result of early interference with brain neurotransmitters, using these drugs, are not gross physical malformations but are in fact subtle behavioral and neurological symptoms such as hyperactivity, emotional lability, attentional distractability and sleep disturbances, similar to symptoms observed in the minimal brain dysfunction syndrome. PMID- 3099592 TI - Micro anion exchange chromatography of carbohydrate-deficient transferrin in serum in relation to alcohol consumption (Swedish Patent 8400587-5). AB - A new simplified and rapid method for detection and quantitation of "carbohydrate deficient transferrin" in serum is described. The method is based on isocratic anion exchange chromatography of isotransferrins in disposable microcolumns followed by a double antibody transferrin radioimmune assay. This technique, which separates all transferrin components isoelectric above pH 5.65, showed a very good reproducibility and accuracy with a coefficient of variation between 5 and 9%. 77 alcoholic patients could be clearly separated from 80 healthy "normal consumers" and 33 total abstainers with a specificity of 100% and a sensitivity of 91%. The values were significantly correlated to the amount of alcohol consumed during the latest month, and declined in abstaining alcoholics with a mean biological half-life of 17 days. Elevated levels occasionally appeared in healthy individuals after daily consumption of 60 g of ethanol during a 10-day period. In a sample of 187 patients with nonalcohol-related conditions only 2% false-positive values were found. This method is suggested as a potential tool for detecting and monitoring alcohol abuse. PMID- 3099588 TI - Early total parenteral nutrition in acute pancreatitis: lack of beneficial effects. AB - To determine the effect of early aggressive parenteral support in pancreatitis, 54 patients with acute pancreatitis were randomized to receive either conventional therapy (control group) or conventional therapy plus the institution of total parenteral nutrition within 24 hours. The two groups were similar demographically. The total parenteral nutrition group had a significantly higher rate of catheter-related sepsis than did an additional group of contemporaneous patients without pancreatitis who received total parental nutrition (10.5 percent and 1.47 percent, respectively; p less than 0.01). There was no advantage to the use of early total parenteral nutrition; that is, there was no difference in the number of days to oral intake, total hospital stay, or number of complications of pancreatitis. Patients with zero or one Ranson's criterion on admission were more likely to be eating by the seventh hospital day than were those with two or more Ranson's criteria (80 percent and 54 percent, respectively; p less than 0.05). The early institution of total parenteral nutrition in patients with acute pancreatitis did not appear to improve the outcome. Its use should be limited to prolonged periods of no oral intake or treatment of a specific complication, such as a pseudocyst. PMID- 3099593 TI - [High frequency jet ventilation as a form of artificial respiration in thoracic and abdominal surgery. Clinical experiences]. AB - A total of 66 patients undergoing thoracic and abdominal surgery were ventilated with high-frequency jet ventilation (HFJV), using frequencies of 100 cycles/min (n = 33), 150 cycles/min (n = 21), and 200 cycles/min (n = 12). Inspiratory time was 30% and FIO2 0.4 (abdominal) and 0.5 (thoracic) respectively. Normocarbia required minute-volumes of 215.0 +/- 47.4 ml/kg (100 cycles/min), 256.0 +/- 39.2 ml/kg (150 cycles/min), and 298.0 +/- 41.0 ml/kg (200 cycles/min) respectively. With HFJV paO2-values were significantly below those under conventional ventilation (118.5 mmHg versus 153.2 mmHg; 137.5 mmHg versus 165.5 mmHg; 136.4 mmHg versus 156.7 mmHg). Heart rate, arterial blood pressure, and central venous pressure showed no differences. With HFJV 8 patients revealed paO2-values below 80 mmHg, 3 patients had to be returned to conventional ventilation because of severe hypoxia. HFJV is considered of no advantage over conventional ventilation and may cause prodigious hypoxia in patients with pulmonary dysfunction. Therefore, HFJV cannot be recommended in thoracic and abdominal surgery. PMID- 3099594 TI - [Use of the double-lumen tracheostomy tube (Tracheopart) in bronchial stump insufficiency in long-term artificial respiration. Case report]. AB - In long-term artificial respiration an insufficiency of the bronchial stump after pneumectomy must be considered as a result of the positive pressure respiration. Respirator treatment can be continued by means of a twin-lumen tracheostomy tube, the bronchial fistula being relieved of the stress while offering it an opportunity to close spontaneously. Good experience collected with the practical use of this method points to its suitability in prophylaxis as well. PMID- 3099595 TI - [Heat stroke. Therapeutic considerations in a case]. AB - Heat stroke is an acute life-threatening disease requiring therapy immediate to cope with the severe pathophysiologic disturbances. Rapid lowering of the high core temperature seems to be the most important therapeutic measure. Besides methods of physical cooling, Dantrolene should also be used in this hyperthermic state. By consequent lowering of the body temperature it will be possible to stabilise circulation and minimise disease-related injuries of different organs. PMID- 3099596 TI - A solid-phase assay for the phosphorylation of proteins blotted on nitrocellulose membrane filters. AB - A new procedure for the phosphorylation and assay of phosphoproteins is described. Proteins are solubilized from tissue samples, separated by polyacrylamide gel electrophoresis, transferred onto nitrocellulose membrane filters, and the blotted polypeptides are phosphorylated with the catalytic subunit of cyclic AMP (adenosine 3':5'-monophosphate)-dependent protein kinase. The method was developed for the assay of dephosphosynapsin I, but it has also proven suitable for the phosphorylation of other proteins. The patterns of phosphorylation of tissue samples phosphorylated using the new method are similar to those obtained using the conventional test tube assay. Once phosphorylated, the adsorbed proteins can be digested with proteases and subjected to phosphopeptide mapping. The phosphorylated blotted proteins can also be analyzed by overlay techniques for the immunological detection of polypeptides. PMID- 3099598 TI - [Indications for determination of acrosin]. AB - Assessment of acrosin activity for evaluation of acrosomal functions and the fertilizing capacity of spermatozoa is a suitable method within the diagnostic workup of male sterility in selected cases. Indications for determination of acrosin activity are cases with teratozoospermia and polyzoospermia. In addition, demonstration of sufficient amounts of acrosin activity in idiopathic sterility or in cases with an unknown male sterility factor and before in vitro fertilization may exclude severe disturbances of the sperm acrosome. PMID- 3099597 TI - Meningeal cells influence cerebellar development over a critical period. AB - We have investigated the influence of meningeal cells on the development of the cerebellum by destroying these cells with 6-hydroxydopamine in hamsters of different ages. The ensuing foliation and lamination disruption in the cerebellar vermis is attributed to a disintegration of the cerebellar surface and a disorganization of the glial scaffold of the cerebellar cortex due to a loss of meningeal-glial interaction in stabilizing the extracellular matrix at the glia limitans superficialis (v. Knebel Doeberitz et al. 1986, Neuroscience 17:409 426). The severity of these cerebellar defects is correlated with the ontogenetic stage at which meningeal cells are destroyed, being greatest after treatment at postnatal day 1 and decreasing thereafter until day 5 and beyond, when no abnormalities occur, although all meningeal cells are destroyed throughout. The absence of cerebellar defects after destruction of meningeal cells at day 5 or later is associated firstly with the end of the period of branching morphogenesis of the cerebellum when all folial primordia are established, and, secondly, with the maturation of the glia limitans superficialis. These findings indicate that meningeal cells stabilize the cerebellar surface and glial scaffold over a critical period that ends, when the pattern of cerebellar foliation is established, and when the glia limitans superficialis has reached a mature state. Beyond this stage glial end-feet alone are sufficient to maintain the epithelial integrity of the cerebellum. PMID- 3099599 TI - Pharmacokinetics of alfentanil in chronic renal failure. AB - The pharmacokinetics of alfentanil were studied during general anesthesia in nine patients with renal failure and in ten patients with normal renal function. All patients received 0.05 mg/kg alfentanil as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 8 hr, using a specific radioimmunoassay technique. Protein binding was measured by equilibrium dialysis. Elimination half-life and plasma clearance were similar in both groups. The volume of distribution at steady state was greater (P less than 0.02) in patients with renal failure (405 +/- 86 ml/kg) than in patients with normal renal function (281 +/- 97 ml/kg). Patients with renal failure had a higher (P less than 0.01) alfentanil plasma free fraction (0.19 +/- 0.06) than patients with normal renal function (0.11 +/- 0.03). When kinetic parameters were corrected for protein binding, the unbound volume of distribution and the free drug clearance were unchanged in patients with renal failure. These results suggest that the modification of alfentanil free fraction in renal failure does not induce any change in elimination but may influence the distribution of alfentanil. PMID- 3099600 TI - Comparative maternal, fetal, and neonatal effects of chloroprocaine with and without epinephrine for epidural anesthesia in obstetrics. AB - The effects of epidural chloroprocaine with and without 1:200,000 epinephrine during labor and delivery on uterine activity, progress of labor, fetal heart rate, maternal blood pressure, newborn Apgar scores, neonatal acid-base status, and the Neurologic and Adaptive Capacity Scoring System (NACS) were compared in 28 parturients. Patients in group I (n = 14) received 2% chloroprocaine with 1:200,000 epinephrine and patients in group II (n = 14) received 2% plain chloroprocaine. Addition of epinephrine to chloroprocaine had no significant effects on uterine activity, duration of first or second stages of labor, or fetal heart parameters. Apgar scores, neonatal acid-base status, and the NACS were equally good in the two groups. Duration of analgesia was significantly longer in group I than in group II patients (76 +/- 3.8 vs 42.9 +/- 1 min, P less than 0.001). We conclude that addition of epinephrine to chloroprocaine during epidural anesthesia in the normal parturient has no adverse effects on mother, fetus, neonate, or the progress of labor and that it significantly prolongs the duration of anesthesia. PMID- 3099603 TI - A comparison of alfentanil pharmacokinetics in children and adults. AB - The pharmacokinetics of alfentanil have been studied in eight children aged between 4 and 8 yr and five adults during general anesthesia. All patients were given 20 micrograms/kg alfentanil as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 6 h by radioimmunoassay. Plasma protein binding was measured by equilibrium dialysis using tritiated alfentanil. The optimal pharmacokinetic model for alfentanil was an open two-compartment model. Total apparent volume of distribution (Vdss) was 457 +/- 160 ml/kg in adults and 163 +/- 110 ml/kg in children (P less than 0.01). When recalculated by surface area Vdss was still decreased in children (P less than 0.01). Plasma clearance (Cl) was similar in the two groups. Terminal elimination half-life was significantly shorter in children (40 +/- 9 min) than in adults (97 +/- 22 min; P less than 0.01). The shorter elimination half-life could be due to the smaller total apparent volume of distribution in children. Plasma protein binding was comparable between children and adults and could not explain the smaller volume of distribution in children. It is suggested that the smaller volume of distribution of alfentanil in children is a result of the decreased percentage of fat tissue in children. PMID- 3099605 TI - Extracts from Sarcocystis gigantea macrocysts are mitogenic for human blood lymphocytes. AB - Extracts were prepared from macrocysts of Sarcocystis gigantea, an animal parasite, by sonication and high speed centrifugation. Mononuclear cells were obtained from the blood of 14 adults and 5 newborns and used for transformation assays. Addition of Sarcocystis extracts (equivalent to 400 micrograms protein/ml) to these cells increased the lymphocyte proliferation approximately 71 fold over the background. The control with Pokeweed mitogen (5 micrograms/ml) gave a stimulation index of 58. There was no difference in the response to the Sarcocystis extract between the lymphocytes of adults and those of newborns. This findings show that the effect of the extract is mitogenic and not due an anamnestic reaction. PMID- 3099602 TI - Dependence of lidocaine potency on pH and PCO2. AB - Lidocaine solutions with different concentrations of CO2, NaOH, and HCl in two buffering systems were applied to frog sciatic nerves. The peak of the compound action potential (APc) and the firing threshold for single axons were measured. The amount of lidocaine required at steady state to double the firing threshold of single fibers or to reduce the peak of the APc by 40% was used as the index of potency. Acidification with CO2 increased potency (less lidocaine was needed to achieve either criterion), whereas acidification with HCl diminished potency, as compared with alkaline conditions. These results were true whether or not the perineurium was present. Frequency-dependent block (Bf) increased in acid conditions produced by CO2, whereas Bf was less under acid conditions produced with HCl (P less than 0.02). The experiments indicate that CO2 potentiates conduction block with lidocaine either by a direct effect on the membrane or by its indirect action on intracellular pH, but not from effects on the extracellular pH. PMID- 3099604 TI - Population pharmacokinetics of alfentanil: the average dose-plasma concentration relationship and interindividual variability in patients. AB - The population pharmacokinetic parameters describing the plasma concentration versus time profile of alfentanil in patients undergoing general anesthesia were determined from 614 plasma concentration measurements collected in four previously reported studies with a total of 45 patients. A nonlinear regression analysis evaluating the effect of six concomitant variables revealed a significant influence of body weight on the volume of the central compartment (Vc), and a decrease with age of total body clearance (CL) and of redistribution rate from the deep compartment (k31). A small but significant effect of sex on the Vc was also observed. The duration of anesthesia and the concomitant administration of inhalational anesthetics had no effect on alfentanil pharmacokinetic parameters. The mean CL and Vc for alfentanil in a 70-kg male, aged less than 40 yr, were estimated as 0.356 l/min and 7.77 l, respectively. After correction for age, body weight, and sex, the remaining interindividual variability of alfentanil kinetics (expressed as coefficient of variation) was 48% for CL and 33% for Vc. These population pharmacokinetic parameter estimates should increase the accuracy of predicting concentration-time profiles for intravenous alfentanil infusions. A computer program is presented that allows prediction of the alfentanil plasma concentration and the 68% interval limits of the prediction from the study data analysis. PMID- 3099606 TI - [Acute ischemia of the extremities: apropos of a case of ergotamine tartrate poisoning]. PMID- 3099608 TI - Epidemiology: expanding applications. PMID- 3099609 TI - Scrubby Bear can make an impact on your community. PMID- 3099607 TI - Microbial growth in clinically used enteral delivery systems. AB - Potential contamination of enteral formulas has led to the development of policies limiting formula hangtimes. However, enteral administration bags can easily become contaminated during formula refilling. We prospectively studied enteral formula contamination when the hangtime of a prefilled 1000 ml pouch was compared with the standard 4-hour hangtime of a refilled enteral administration bag. Samples of formula collected from different locations along the enteral delivery system were cultured during 57 days of enteral hyperalimentation in 19 patients. The overall enteral formula contamination rate was 61%, where the greatest microbial growth occurred in reconstituted enteral formulas. The presence of microbial growth did not differ between canned formulas administered according to a 4-hour hangtime and the prefilled pouch. Greatest growth in all cases was at the distal tubing hub, where contamination during system manipulation or from the patient probably occurred. Use of prefilled enteral administration bags may delay formula contamination in the administration reservoir. A change in equipment design that would decrease the need to manipulate feeding sets or feeding tube connections should be further investigated. PMID- 3099610 TI - Non-IgE antibody mediated mechanisms in food allergy. AB - Food sensitivity or intolerance is not necessarily based on the Type I allergic reaction. Non-IgE antibody reactions, complement-dependent reactions, enzyme deficiencies such as lactase and non-immunologic histamine release (such as with some sea foods) have been described. Even the detection of specific antibodies on their own does not necessarily indicate that a given symptom is due to that antibody. Food allergy nevertheless exists. It is important that those observers fortunate enough to see many cases document their observations carefully and eventually publish them for the education of their less fortunate colleagues. Is food allergy more common in infants and young children? What happens as they grow older? How often is atopic eczema due to food allergy? Why are some foods more likely to be implicated than others? Does a negative RAST result eliminate the diagnosis or a positive one confirm it? Until the answers to these and other questions are known, the mainstay of diagnosis will be the history, and that of treatment will be the elimination diet. PMID- 3099601 TI - Glucose metabolism during liver transplantation in dogs. AB - Arterial and hepatic venous blood levels of glucose were studied in 12 dogs during orthotopic liver transplantation performed under ketamine anesthesia without exogenous glucose administration. During the early part of surgery, arterial blood glucose levels were stable: 161 +/- 12 mg/dl (mean +/- SEM) after laparotomy and 183 +/- 16 mg/dl 5 min before the anhepatic stage. During the anhepatic stage, arterial blood glucose levels decreased progressively to 135 +/- 9 and 88 +/- 8 mg/dl, 5 min in the anhepatic stage and 5 min before reperfusion of the graft liver, respectively (P less than 0.05). Reperfusion of the graft liver resulted in an increase in arterial glucose levels to 206 +/- 17 and 240 +/ 24 mg/dl, 5 and 30 min after reperfusion, respectively (P less than 0.05). Hepatic venous blood glucose levels increased after reperfusion (405 +/- 37 and 346 +/- 41 mg/dl, 5 and 30 min after reperfusion, respectively) and were significantly higher than in arterial blood (P less than 0.05). Arterial plasma insulin, measured in five animals, did not change significantly during the procedure, whereas plasma glucagon levels, stable during the preanhepatic and anhepatic stages, increased steadily after reperfusion of the graft liver, from 66.1 +/- 14.2 to 108.4 +/- 38.1 pg/ml (P less than 0.05). This study shows that in dogs with ketamine anesthesia mild hypoglycemia occurs during the anhepatic stage of liver transplantation without exogenous glucose administration followed by hyperglycemia on reperfusion of the graft liver, possibly secondary to the release of glucose from the donor liver. PMID- 3099611 TI - Group comparative trial of cromolyn sodium and terfenadine in the treatment of seasonal allergic rhinitis. AB - Cromolyn sodium nasal spray for 6 weeks together with terfenadine for 1 week were compared with administration of terfenadine alone for 6 weeks. During the first week, significantly greater relief of nasal symptoms was achieved with the combination. Overall the results indicated that cromolyn sodium tended to be more beneficial than terfenadine. PMID- 3099612 TI - Evidence of paratuberculosis in Ohio's white-tailed deer, as determined by an enzyme-linked immunosorbent assay. AB - An enzyme-linked immunosorbent assay (ELISA) was developed and used to detect antibodies to Mycobacterium paratuberculosis in serum samples obtained in December of 1983 from 954 hunter-killed white-tailed deer (Odocoileus virginianus) in 13 Ohio counties. Positive or negative status was determined by calculating a signal-to-noise ratio, a ratio between the optical density of the test serum and negative reference sera; a ratio of greater than or equal to 3.0 was considered positive. Twenty-four samples (2.5%) were found to be assay positive, using this method. A statistically significant difference among age groups was found, with those less than or equal to 6 months of age having a lower proportion of positives. Differences by sex were not observed. To determine the validity of the ELISA in deer, serum samples from 46 fallow (Dama dama) and axis deer (Axis axis) harvested from a known infected population were tested by ELISA and agar-gel immunodiffusion. The agar-gel immunodiffusion test showed evidence of exposure of the deer to M paratuberculosis or a related antigen. The ELISA closely approximated the prevalence of paratuberculosis infection as previously determined by fecal culture in this population. As a result of these tests, it was concluded that free-ranging Ohio deer have been infected with M paratuberculosis or exposed to a closely related antigen. PMID- 3099614 TI - Antibody-mediated suppression of erythropoiesis in dogs with red blood cell aplasia. AB - Eight dogs with acquired RBC aplasia were studied. Unfractionated sera and serum immunoglobulin G fractions were examined for the presence of erythroid progenitor cell inhibitors. A serum immunoglobulin G inhibitor directed against precursors of erythroid colony-forming units was detected in 3 of 5 dogs that were direct Coombs' test-negative and in 1 of 3 dogs that were direct Coombs' test-positive. Sera from these dogs were treated with binary ethyleneimine to inactivate any viruses present. The inhibitory effects of the treated serum on erythroid colony forming units was not ameliorated. PMID- 3099613 TI - Comparison of the susceptibility of Brucella abortus isolates obtained before and after cows were treated with oxytetracycline and streptomycin. AB - Eight isolates of Brucella abortus were obtained from cows before and after they were treated with oxytetracycline and streptomycin. The susceptibility to these antibiotics was determined by broth-dilution minimal inhibitory and minimal lethal concentrations. Differences were not found in the minimal lethal concentrations of oxytetracycline or streptomycin in isolates obtained from cows before and after they were treated. This indicates that treatment failures in the cows were not the result of development of resistance to the antibiotics by B abortus. PMID- 3099615 TI - The effect of maternal CO2 breathing on lung development of fetuses in the rabbit. Morphologic and morphometric studies. AB - We have examined male fetuses from rabbits exposed from Day 21 to Day 28 of gestation to 8% CO2 for 8 h each day. Fetuses of CO2-exposed mothers weighed less and had lungs that weighed less but when expressed per unit body weight were unchanged. Distended lung volumes were greatly increased in the CO2 group. Light microscope morphometry showed more mature lungs with increased volume proportion of air spaces, decreased air-space wall, and decreased nonparenchyma in CO2 exposed animals. Individual air-spaces were larger, gas exchanging surface area was increased, air-space walls were thinner, and higher ratios of mature to immature crests were found. Electron microscope morphometry showed decreased glycogen in alveolar Type II cells and increased volume proportion of lamellar bodies in the CO2 group. Type II cells were more cuboidal. We interpret these changes to represent increased tissue and cellular maturation in fetuses whose mothers breathed CO2. We speculate that the changes were brought about by increased fetal respiration, which may cause increased stretch and distention of the lung. Alternative mechanisms are discussed. PMID- 3099616 TI - Time course of change in ventilatory response to CO2 with long-term CPAP therapy for obstructive sleep apnea. AB - Nineteen subjects with the obstructive sleep apnea syndrome (10 with daytime arterial CO2 tension 44 mm Hg or higher) were treated with long-term nocturnal continuous positive airway pressure. The ventilatory response to CO2 (Read's method) was measured in triplicate prior to treatment and after 1, 2, 3, 7, and 14 or more nights of therapy. Seven subjects were tested on at least 4 occasions. For each test, slope of the response line and position of the response line (ventilation at a PCO2 of 60 mm Hg) were calculated. The subjects with initial high daytime CO2 showed no change in slope of response with treatment but showed a progressive increase in ventilation at any given degree of PCO2. Ventilation at a PCO2 of 60 mm Hg increased from a mean of 20.0 +/- 1.3 SEM L/min by 8.0 +/- 2.5 SEM L/min after 2 nights of therapy (p less than 0.05, two-way analysis of variance), and by 16.2 +/- 1.9 L/min after 2 wk or more (p less than 0.01). On average, there was no significant change in either slope or position of response in the subjects with initially normal daytime PCO2. We conclude that airway obstruction in sleep (in obstructive sleep apnea syndrome) leads in some subjects to respiratory failure in the daytime, with a left shift in the ventilatory response to CO2, and that this changes is usually reversible during the next several days. PMID- 3099618 TI - Complications of biliary surgery. AB - Procedures on the gallbladder and extrahepatic biliary tract were the most frequently performed operations in a series of 1500 consecutive abdominal operations done in community hospitals. The operative mortality rate for elective cholecystectomy was 0.3 per cent. The complication rate was 21.4 per cent for cholecystectomy. Patients requiring emergency cholecystectomy had significantly more urinary tract and intra-abdominal problems than those patients who underwent surgery electively. Operative cholangiography was performed during 20.3 per cent of the elective cholecystectomies. There were no biliary tract complications among the cholecystectomy patients who had cholangiography. When this study was not performed, 1.5 per cent of the patients had postoperative bile duct problems. Older surgeons (greater than 60 years of age) and high volume surgeons (greater than 300 cases/year) were significantly less likely to employ cholangiography. The mortality rate for elective common duct exploration was 4.4 per cent, with a complication rate of 60 per cent. There was a 13.3 per cent incidence of retained stones after choledochotomy, though this problem was readily managed by percutaneous extraction through the T-tube tract. Complex biliary tract procedures were performed electively without mortality, though the complication rate for these procedures was 35.3 per cent. Two-thirds of the patients undergoing complex biliary tract operations on an emergency basis died. Board certified general surgeons had the same mortality and complication rates for cholecystectomy as well as common bile duct exploration. Noncertified surgeons had significantly more intraabdominal complications after complex biliary tract procedures compared to their board certified colleagues. PMID- 3099617 TI - Recombinant gamma, alpha, and beta interferon regulation of human lung fibroblast proliferation. AB - To further understand the processes controlling tissue fibrosis, we characterized the effect of recombinant gamma, alpha A, alpha D, and beta interferons on the proliferation of slowly and rapidly proliferating normal human lung fibroblasts. In addition, we investigated the role of fibroblast prostaglandin production in mediating the effects that were noted. Gamma interferon was capable of bidirectional modulation of fibroblast growth since it stimulated the proliferation of quiescent cells and inhibited the proliferation of rapidly proliferating cells. In contrast, alpha A, alpha D, and beta interferons did not stimulate the proliferation of quiescent cells, but did inhibit the proliferation of rapidly proliferating cells. Gamma, alpha A, alpha D, and beta did not stimulate E series prostaglandin production by rapidly proliferating fibroblasts, and blocking fibroblast prostaglandin production did not reverse the inhibition of fibroblast growth caused by these interferons. Thus, gamma interferon can stimulate or inhibit, whereas alpha A, alpha D, and beta interferons only inhibit the growth of normal human lung fibroblasts. In addition, the inhibition of fibroblast growth caused by all 4 interferons appears to be independent of fibroblast prostaglandin production. PMID- 3099619 TI - Diverticular disease of the cecum and ascending colon. A review of 881 cases. AB - A total of 881 cases of diverticula of cecum and the ascending colon were reviewed, including 30 new cases at the authors' institution. The average patient age was 43.6 years. The preoperative diagnosis was correct in only 7 per cent of the cases. Appendicitis accounted for 68 per cent of the preoperative diagnoses. Even at the time of surgery, the diagnosis was correct in only 58.7 per cent. Carcinoma was incorrectly diagnosed in 37.2 per cent. Operative procedures varied markedly. Diverticulectomy was performed in 28.2 per cent of the cases, 3.6 per cent had invagination of the diverticula, and 37.6 per cent had right hemicolectomy. The overall mortality rate was 2.5 per cent. The authors advocate local resection of the diverticulum, when possible, and a right hemicolectomy or segmental resection when the diagnosis is in doubt or when local resection or invagination will jeopardize the ileocecal valve or the blood supply to the intestine. PMID- 3099620 TI - Feeding jejunostomy (versus gastrostomy) passes the test of time. AB - The authors previously reported a higher incidence of early postoperative complications after feeding gastrostomy compared to jejunostomy, prompting the recommendation of jejunostomy for chronic enteral feeding. Long-term follow-up has since been obtained on these 31 patients and an additional 25 patients undergoing surgical feeding procedures. The 26 feeding gastrostomies were 16 Stamm, eight permanent mucosal-lined, and two Witzel. The 30 feeding jejunostomies consisted of 19 Roux-en-Y, nine Stamm, and two Witzel. Patients with gastrostomy have had a mean follow-up of 100 days. Adverse events have occurred in 15/26 (58%), including 9 patients with pulmonary aspiration (35%), two of which were fatal. Twenty-three additional patients have died of underlying diseases. All 11 patients with tube jejunostomy died of underlying diseases within 4 months of surgery. The complication rate was 36%, including pulmonary aspiration in both patients with Witzel jejunostomy. The 19 patients with Roux-en Y jejunostomy have had mean follow-up of 169 days. Complications have occurred in 9 patients (47%); 16/19 patients (mean age 55 years) have died of underlying disease. The mean age of the patients still alive is 35 years. Feeding jejunostomy has a lower incidence of complications, especially pulmonary aspiration, than gastrostomy. Stamm jejunostomy should be used for enteral feeding in older patients and in patients with short life expectancy. In younger patients requiring lifelong enteral feeding, Roux-en-Y jejunostomy should be used. PMID- 3099621 TI - Epidemic non-A, non-B hepatitis in patients from Pakistan. AB - Epidemic non-A, non-B hepatitis was diagnosed in three young Pakistani men during a 10-month period at the Los Angeles County-University of Southern California Medical Center. All three patients had recently visited or lived in Karachi, Pakistan. None had serologic markers of hepatitis B virus infection or IgM antibody (acute-phase) to hepatitis A virus. A liver biopsy from one patient showed marked cholestasis and cholangiolar transformation of hepatocytes, a pattern previously described in patients with epidemic non-A, non-B hepatitis. Immune electron microscopy of a stool specimen obtained from this patient 10 days after the onset of symptoms showed virus-like particles, 27 nm in diameter, that were specifically aggregated by antibody contained in acute-phase sera from the three Pakistani patients, from patients with non-A, non-B hepatitis in Burma and Nepal, and from an experimentally infected marmoset. Recognition of three separate cases of probable epidemic-type non-A, non-B hepatitis in patients at one institution during such a short time suggests that Pakistan is endemic for this infection and that the disease may be more commonly spread to the United States than is now presumed. PMID- 3099622 TI - Transdermal nitroglycerin and nitrate tolerance. PMID- 3099623 TI - Contribution to the study of nigrostriatal dopaminergic neuron activity using electrochemical detection of dopamine release in the striatum of freely moving animals. PMID- 3099624 TI - Granulocyte precursor cell studies in Schistosoma mansoni patients with eosinophilia. AB - Eosinophilia is a common clinical presentation in patients with helminthic infections. A study was designed to determine the mechanism(s) for selective or preferential differentiation of precursor cells into mature eosinophils (eos). Thus, experiments were performed to delineate the frequency of colony forming units of eos (CFU-eos) in the peripheral blood of Egyptian patients with active Schistosoma mansoni infection with eosinophilia and normal healthy individuals. The number of CFU-eos among the nonadherent mononuclear cell population was assessed in a double layer soft agar culture with autologous unfractionated mononuclear cells serving as a source of colony stimulating factor(s). Following 14 days of incubation, discrete colonies were distinguished morphologically as eosinophilic, neutrophilic, or mixed. Results indicated a two-fold increase in the total number of colonies per 10(6) cultured nonadherent cells in patients with S. mansoni infection when compared to the number of colonies obtained with adult normal volunteers (57 +/- 10 vs. 24 +/- 4; P less than 0.025). However, the frequency of CFU-eos and CFU-neut was similar in patients and normal individuals (66 +/- 3 vs. 59 +/- 8 percent CFU-eos; 30 +/- 4 vs. 35 +/- 6 percent CFU-neut). These data suggest that: eosinophils may differentiate from progenitor cells at other anatomical sites; there may be an increase in the half life of mature eosinophils in patients; there is no strict correlation between the frequency of progenitor cells and the number of differentiating mature cells of this lineage at least as measured by this in vitro assay; and the in vitro assay may not quantitatively reflect the in vivo differentiating capacity of progenitor cells. PMID- 3099625 TI - Mechanism of factor VIII inactivation by human antibodies. IV. Antibody binding prevents factor VIII proteolysis by thrombin. AB - Factor VIII activation by thrombin is the result of a proteolytic cleavage of the procoagulant component. These studies examine the effect of human antibody on this activation step in a solid phase immunoadsorbent assay system. Radiolabeled factor VIII antibody: factor VIII protein immune complexes were bound to agarose beads by mouse monoclonal antifactor VIII R:Ag antibody. The incubation of these bound labeled immune complexes with high ionic strength buffers (1 M NaCl, 0.24 M CaCl2), or with acidic buffers (0.01 M glycine-0.1 M NaCl, pH 3.0 or 3.5), or with trypsin (1, 5, and 20 mg per ml) dissociated 14 to 62 percent of the bound radiolabel. Thrombin at a concentration of 0.05 U per ml, however, only dissociated 2.9 percent of the label, an amount not significantly different than borate buffered saline control. It is concluded that inactivation of factor VIII is the result of human antibody inhibition of thrombin-induced proteolysis of factor VIII procoagulant protein. PMID- 3099626 TI - [Influence of gonadotropins on inhibin secretion]. AB - Inhibin is produced by Sertoli cells in the male and by granulosa cells in the female. Follicular-stimulating hormone acts directly to stimulate production whereas luteinizing hormone exerts an indirect effect by stimulating production of androgens which themselves activate synthesis and release of inhibin. Prolactin has no effect on inhibin. These interpretations, derived from numerous in vivo and in vitro studies, explain why inhibin is not secreted in the hypophysectomized animal. Interruption of spermatogenesis by ligature of deferens canals, by experimental cryptorchidism in the rat, and in human primary azoospermias, provokes a reduction in production of inhibin and an increased secretion of FSH. The second must be the consequence of the first. Restoration of normal spermatogenesis results in normal production of inhibin. Biochemical mechanisms linking spermatogenesis and inhibin production are still unknown. PMID- 3099627 TI - Detoxifying activities in alveolar macrophages of rats treated with acetylcysteine, diethyl maleate and/or aroclor. AB - Single or sequential treatment of rats with the thiol N-acetyl-L-cysteine (NAC), the glutathione depletor diethyl maleate (DEM) and the enzyme inducer Aroclor 1254 (AR) produced several significant variations on metabolic activities of pulmonary alveolar macrophages (PAM). Specifically, all three compounds elicited an increase in some oxidoreductase activities, including the two dehydrogenases involved in the hexose monophosphate shunt (G6PD and 6PGD) and NADH- or NADPH dependent diaphorases. Diaphorase activities were especially increased by sequential treatments with AR and DEM or with DEM and NAC. Both NAC and AR also stimulated other detoxifying mechanisms, such as those related to GSH S transferase activity and to the NADPH-dependent reduction of hexavalent chromium. Therefore, all the monitored parameters were significantly enhanced not only by the enzyme inducer, but also by the thiol, demonstrating its protective role in the biotransformation of mutagenic/carcinogenic compounds. PMID- 3099628 TI - Sensitivity to anthracyclines in P388/dx leukaemia cells. AB - It has been demonstrated previously that neoplastic cells with reduced oxygen consumption are more sensitive to doxorubicin8. We have examined the relationship between doxorubicin sensitivity and oxygen consumption of P388 murine leukaemia cell line (P388) and of a doxorubicin resistant subline (P388/dx). Oxygen utilization by P388/dx cells was higher than that found in the sensitive line. A variety of calcium antagonists, including channel blockers and intracellular antagonists (verapamil, trifluoperazine, dantrolene, TMB-8, nitrendipine) or membrane acting drugs (lucensomycin), enhanced the cytotoxic activity of doxorubicin in P388 and markedly in P388/dx subline. This action was accompanied by a reduction of oxygen consumption more pronounced in the resistant cells. These findings emphasize the correlation between oxygen uptake, instead of calcium dependent processes, and doxorubicin responsiveness. The calcium ionophores A 23187 failed to alter doxorubicin activity in P388 and P388/dx leukaemia. PMID- 3099629 TI - Metabolism of N-nitrosodimethylamine and N-nitrosomethylbenzylamine in domestic fowls: DNA alkylation and potential target sites for carcinogenicity. AB - The metabolism and reaction with DNA of N-nitrosodimethylamine (NDMA) and N nitrosomethylbenzylamine (NMBzA) were investigated in chickens. These nitrosamines have been identified in a typical diet consumed in northern Chinese provinces with a high incidence of oesophageal cancer in both, humans and domestic fowls. Following i.m. or oral administration of the 14C-methyl labeled nitroso compounds (16.5 mumol/kg) less than 10% of the total radioactivity was exhaled as 14CO2 within 24 hr. DNA alkylation in chicken tissues was generally low, with highest values in liver (approximately 30 mumol N7-methylguanine/mol guanine) and kidney. In the gastrointestinal tract, concentrations of methylpurines were close to the limit of detection. After oral administration of NMBzA the reaction with DNA was more extensive, in particular in the diverticulum (crop), where N7-methylguanine and 0(6)-methylguanine amounted to 32 and 3.5 mumol/mol guanine, respectively. These values are more than 10-fold lower than those produced by a similar dose in rats, i.e. a species in which NMBzA induces a high incidence of oesophageal carcinomas. The low capacity of the chicken mucosa to bioactivate NDMA and NMBzA argues against these nitrosamines as agents responsible for oesophageal cancer in high risk areas. PMID- 3099630 TI - Selective delivery of high levels of mitomycin C to peritoneal carcinomatosis using a new dosage form. AB - Selective delivery of a high level of Mitomycin C (MMC) in intraperitoneal disseminated lesions was studied using a new dosage form of MMC, called MMC-CH. Intracavitary MMC-CH delivered a much higher level of MMC selectively to intraperitoneal tissues, with a much lower level of MMC in the whole body, in comparison with MMC solution. The index [MMC level in the intraperitoneal organs]: [MMC level in blood] was much higher and increased with time in the MMC CH group, but not in the MMC solution group. PMID- 3099632 TI - Evolutionary idealism: a philosophical foundation for holistic nursing theory. AB - The philosophical tradition of evolutionary idealism is explored as an appropriate metaphysical foundation for holistic nursing science. Some implications of this tradition for theory development, testing, and practice are identified. It is suggested that evolutionary idealism can form an appropriate philosophical foundation for nursing theory development. PMID- 3099633 TI - A case study of theory development: moral behavior in nursing. AB - The theoretical considerations, operationalization of the constructs, and measurement issues of an ongoing program of research designed to explain ethical practice in nursing are presented. They illustrate the constant give and take among research, the empirical world, and theory building. This case study depicts the iterative and complex process of developing constructs and relationships, based on research findings, that explain moral behavior in nursing practice. PMID- 3099634 TI - Intergenerational caregiving: adult caregivers and their aging parents. AB - Theory-generating methodologies can be used to add to our knowledge in areas that are already well researched in addition to areas that have not been extensively studied. The study presented here demonstrates how the grounded-theory method was used to generate a new theory of intergenerational caregiving. Analysis revealed five conceptually distinct, overlapping categories of caregiving. Only one of these includes what is generally considered to be caregiving, that is, hands-on caregiving behaviors or tasks. The other four types are not observable behaviors but are processes crucial to intergenerational caregiving and to an understanding of the experience of intergenerational caregiving. PMID- 3099631 TI - Neuronal and glial proteins in medulloblastomas. II. Heterotransplantation of human medulloblastoma. AB - Seven resected medulloblastomas were inoculated into hereditary athymic (nude) and asplenic athymic (Lasat) mice. From these, only one transplantable tumor line was obtained, in nude mice. We studied the transplanted medulloblastoma immunohistochemically and by electron microscope. In addition, using enzyme immunoassay, the gamma-enolase contents of the transplanted medulloblastomas were measured and the results were compared with those of transplanted glioblastomas. Neurofilament proteins (NF68Kd, NF160Kd) and gamma-enolase positive cells were maintained in the successful transplants of medulloblastomas, but the GFAP positive cells were lost. Under the electron microscope, a few cells with ten nanometer intermediate filaments and microtubules were observed in the transplanted tumor. The medulloblastoma possesses some of the neuronal characteristics which are maintained in the transplants in nude mice. PMID- 3099635 TI - Toward a theory of helpfulness for the elderly bereaved: an invitation to a new life. AB - The purpose of this study was to generate a theory of helpfulness for the elderly bereaved. The theory is grounded in data from responses of 30 participants concerning the advice they would give others who have lost a spouse and how others were helpful to them. Participants responded during six interviews following death of their spouses. A content analysis of responses was the basis of a dialectical theory of helpfulness: An Invitation to a New Life. PMID- 3099638 TI - Components of courage in chronically ill adolescents: a phenomenological study. AB - Although courage is an important variable when clients successfully deal with hospitalization and illness, the concept is contradictory and ill-defined in nursing and other literature. The phenomenological approach and research method has been suggested as one means of concept clarification and theory development. Using the phenomenological approach, this study asked: What is the essential structure of the lived experience of courage in chronically ill adolescents? Nine chronically ill adolescents participated in an open-ended, audiotape-recorded interview, describing their subjective experiences of courage. The descriptions were analyzed phenomenologically. Significant statements were extracted, meanings formulated, and themes identified. Thirty-one theme clusters in nine categories emerged from which an essential structure of courage in chronically ill adolescents was derived. PMID- 3099637 TI - Identity of self as infertile: an example of theory-generating research. AB - This article presents results of a study using grounded-theory methodology to explore the meaning of infertility to those persons experiencing it. Thirty-two persons were interviewed, including 15 married couples and two married women whose husbands were either unable or unwilling to participate in the study. Forty five semistructured interviews were conducted, as each person was interviewed separately and 13 couples were interviewed conjointly. Through the ongoing process of data collection and analysis, a substantive grounded theory was generated, with a core concept being that as persons experience unwanted infertility they take on a central identity of themselves as infertile. The process of taking on and managing this identity is described. PMID- 3099636 TI - Relapse among ex-smokers: an example of theory derivation. AB - Theory derivation, the use of analogous concepts from other disciplines to derive theory about a particular phenomenon, has been described as an effective strategy for building nursing theory, especially where existing theory bases are limited. This article provides a detailed, step-by-step description of how the theory derivation process was used to develop a theory of smoking relapse from an analogous theory of recovery after alcohol abuse. Empirical testing revealed partial support for the derived theory. Advantages and limitations of theory derivation as a strategy for constructing nursing theory are described. PMID- 3099639 TI - Genetic analysis and penicillin-binding protein alterations in Neisseria gonorrhoeae with chromosomally mediated resistance. AB - Eight recent isolates of Neisseria gonorrhoeae with high-level non-beta-lactamase mediated penicillin resistance were investigated. The penicillin-binding proteins of these strains were found to have reduced affinity for radiolabeled penicillin. Testing for known resistance genes showed that these were present in the resistant isolates. Genetic transformation was used to construct strains with increasing levels of antibiotic resistance. Modification of the transformation protocol made it possible to isolate transformants at the highest (penicillin resistant DNA donor) level of resistance. These transformants unexpectedly yielded two distinct penicillin-binding protein patterns when tested. PMID- 3099640 TI - High-level tetracycline resistance in Neisseria gonorrhoeae is result of acquisition of streptococcal tetM determinant. AB - Recently, strains of Neisseria gonorrhoeae have been isolated which are highly resistant to tetracycline (MICs of 16 to 64 micrograms/ml). This resistance was due to the acquisition of the resistance determinant tetM, a transposon-borne determinant initially found in the genus Streptococcus and more recently in Mycoplasma hominis, Ureaplasma urealyticum, and Gardnerella vaginalis. In N. gonorrhoeae, the tetM determinant was located on a 25.2-megadalton plasmid. This plasmid arose from the insertion of tetM into the 24.5-megadalton gonococcal conjugative plasmid. The tetM determinant could be transferred to suitable recipient strains of N. gonorrhoeae by both genetic transformation and conjugation. PMID- 3099642 TI - Golgi-specific localization of transglycosylases engaged in glycoprotein biosynthesis in suspension-cultured cells of sycamore (Acer pseudoplatanus L.). AB - Golgi complex and endoplasmic reticulum (ER) were isolated from suspension cultured cells of sycamore (Acer pseudoplatanus L.) by stepwise sucrose density gradient centrifugation using protoplasts as starting material. The purity of the two organelle fractions isolated was assessed by measuring marker enzyme activities. Localization of glycolipid and glycoprotein glycosyltransferase activities in the isolated Golgi and ER fractions was examined; three glycosyltransferases, i.e., galactosyltransferase, fucosyltransferase, and xylosyltransferase, proved to be almost exclusively confined to the Golgi, whereas the ER fractions contained glycolipid glycosyltransferase. The Golgi complex was further subfractionated on a discontinuous sucrose density gradient into two components, migrating at densities of 1.118 and 1.127 g/cm3. The two fractions differed in their compositional polypeptide bands discernible from Na dodecylsulfate gel electrophoresis. Galactosyltransferase distributed nearly equally between the two protein peaks and xylosyltransferase activities using the endogenous acceptor also appeared to be localized in the two subcompartments. By contrast, fucosyltransferase, engaged in the terminal stage of glycosylation, banded in the lower density fractions. Golgi-specific alpha-mannosidase, which is presumably engaged in the sugar trimming of Asn-N-linked glycoprotein carbohydrate core, was enriched fourfold in specific activity in the fractions of the higher density. The overall experimental results indicate that the cotranslational glycosylation of Asn-N-linked glycoproteins, e.g., polyphenol oxidase (laccase), takes place in the ER, while subsequent post-translational processing of the oligosaccharide moiety proceeds successively in the two physically separable compartments of the Golgi complex. PMID- 3099641 TI - Penetration of aztreonam into cerebrospinal fluid and brain of noninfected rabbits and rabbits with experimental meningitis caused by Pseudomonas aeruginosa. AB - This study examined the penetration of aztreonam into the cerebrospinal fluid (CSF) and brain in noninfected rabbits and rabbits with experimental meningitis caused by Pseudomonas aeruginosa. Animals received either 600 or 1,200 mg of aztreonam administered intravenously over 6 h. Aztreonam did not readily enter the CSF in the absence of meningitis. In noninfected animals, mean concentrations in the CSF ranged from 1.1 to 3.0 micrograms/ml with the 600-mg dose and from 2.3 to 4.7 micrograms/ml with the 1,200-mg dose. In contrast, mean concentrations of aztreonam in the CSF were significantly higher (P less than 0.01) at each sampling time in rabbits with experimental meningitis caused by P. aeruginosa. They ranged from 10.2 to 14.6 micrograms/ml with the 600-mg dose and from 29 to 40 micrograms/ml with the 1,200-mg dose. Although concentrations in the brain measured at 6 h tended to be higher in infected rabbits, this difference was not statistically significant. Aztreonam therapy produced a substantial decline in CSF bacterium counts over 6 h: mean CSF counts decreased 2.4 log10 CFU/ml in the 600-mg dose group and 3.0 log10 CFU/ml in the 1,200-mg dose group. The results of this study suggest that aztreonam may be useful in the therapy of meningitis caused by P. aeruginosa. PMID- 3099643 TI - 6-Epicastanospermine, a novel indolizidine alkaloid that inhibits alpha glucosidase. AB - A second indolizidine alkaloid, epimeric with castanospermine, has been isolated from seeds of the Australian tree Castanospermum australe. The structure was established as 6-epicastanospermine by proton and carbon-13 nuclear magnetic resonance spectroscopy and mass spectrometry. 6-Epicastanospermine was found to be a potent inhibitor of amyloglucosidase, (an exo-1,4-alpha-glucosidase), a weak inhibitor of beta-galactosidase, and not to inhibit beta-glucosidase and alpha mannosidase. These results indicate that glycosidase inhibitory activity cannot be predicted by comparison of the structure and stereochemistry with the appropriate sugars, since 6-epicastanospermine is an analog of mannose and not of glucose. The inhibition of amyloglucosidase was found to be competitive and to be more effective at higher pH values. Castanospermine and 6-epicastanospermine differed in their effect upon the mung bean processing enzymes, glucosidase I and II, in that the former is a potent inhibitor whereas the latter is a very poor inhibitor. Subtle alterations in stereochemistry of these alkaloids can therefore produce significant changes in their biological activity. PMID- 3099644 TI - A comparison of the cytosolic and mitochondrial forms of asparagine/glyoxylate aminotransferase. AB - Asparagine aminotransferase activity was measured in a variety of mouse tissues. The liver had the highest activity--nearly 20 times more than any of the other tissues tested. Hepatic asparagine aminotransferase was found to consist of cytosolic and mitochondrial forms. The mitochondrial form was found to be the predominant form in mouse tissue. Gel filtration chromatography indicated that the mouse enzyme forms have comparable molecular weights of approximately 70,000. While the substrate specificities of the two forms are very different, asparagine was the preferred amino donor for both forms. The relative contribution to the total activity of the hepatic enzyme forms varies with the animal source. Mouse had the highest level of enzyme activity of all animals tested. Ratios of the two enzyme forms also varied greatly not only with the animal source but also with the substrate used and the isolation conditions. PMID- 3099645 TI - Kinetic properties and characteristics of mouse liver mitochondrial asparagine aminotransferase. AB - Mouse liver asparagine aminotransferase has been found to be a mixture of enzyme forms having a cytosolic component and a mitochondrial component. The molecular weight of the mitochondrial enzyme is 70,800. The mitochondrial asparagine aminotransferase is strongly inhibited by aminooxyacetate. It is less affected by D-cycloserine but a small amount of inhibition is observed. Cysteine strongly inhibits the enzyme as do several sulfhydryl modifying reagents. The activities of the cytosolic and mitochondrial aminotransferases have been separated, and the kinetic properties of the mitochondrial form determined. The mouse liver mitochondrial asparagine aminotransferase is fairly specific for asparagine, utilizing very few amino acids as alternate amino donors and none to a great extent. The keto acid specificity is very broad, but glyoxylate is one of the most active amino group acceptors. The kinetic properties of the mitochondrial enzyme are also reported here and the data indicate strong substrate and product inhibition. Abortive complex formation may account for the deviation of the double reciprocal plots from the expected pattern. PMID- 3099646 TI - Stereospecificity of sodium borohydride reduction of pig kidney dopa decarboxylase. AB - Sodium boro[3H]hydride reduction of pig kidney 3,4 dihydroxyphenylalanine decarboxylase followed by complete hydrolysis of the enzyme produced epsilon [3H]pyridoxyllysine. Degradation of this material to 4'-[3H]pyridoxamine and stereochemical analysis with apoaspartate aminotransferase showed that the re side at C-4' of the coenzyme is exposed to solvent. In order to determine the face exposed to the solvent in the external Schiff's base, attempts to trap reaction intermediates were made by reduction with sodium boro [3H]hydride of the holoenzyme in the presence of various substrates or substrate analogs. In all cases, covalently bound radioactive material was found which was identified as epsilon-N-pyridoxyllysine. These results suggest that the internal Schiff's base is in mobile equilibrium with the external Schiff's base and that sodium borohydride reduction displaces this equilibrium, resulting in complete reduction of the internal Schiff's base. PMID- 3099647 TI - [Combination chemotherapy with mitomycin C, adriamycin and cisplatin (MAP) in advanced adenocarcinoma of the lung: clinical effect and renal toxicity]. AB - Fourteen patients with advanced adenocarcinoma of the lung were treated with a combination chemotherapy of mitomycin C, adriamycin and cisplatin (MAP). The overall response rate was 43% with 6 partial responses. The median duration of response was 5.5 months. The median survival for responders was 17 months, versus 9 months for non-responders. Toxicity included nausea and/or vomiting, alopecia, myelosuppression and renal toxicity. The serial measurement of renal tubular function was found to be useful in detecting renal damage caused by cisplatin containing chemotherapy. PMID- 3099648 TI - [In vivo chemosensitivity test for UFT and FT-207. I--Subrenal capsule assay]. AB - A chemosensitivity test for UFT and FT-207, which are used in long-term administration clinically, was investigated for prediction of clinical response. Five transplantation-established human tumor xenograft systems were examined using subrenal capsule assay. Both anticancer agents showed antiproliferative effects according to the total administered dose. Two of 5 tumors were determined to be sensitive to UFT using microscopic measurements following intragastric administration of 1/2 of the LD50 value, while they were shown to be resistant to 5-FU. In these two cases, prolongation of life span by long-term administration of UFT was shown clinically. All these experiments could be performed on condition that the loss of body weight in mice was less than 20%. These results suggest that in the 4-day subrenal capsule assay, clinical responses to long-term administration of UFT or FT-207 are predictable using intragastric high-dose administration which does not induce more than 20% body weight loss in experimental mice. PMID- 3099649 TI - [Effects of intravenous feeding on adjuvant chemotherapy--an experimental study on the distribution of 5-FU after injection of tegafur (1)]. AB - Forty-eight male Donryu rats inoculated with Sato lung cancer were used to experimentally determine the effects of intravenous feeding on the concentrations of the chemotherapeutic agents FT-207 and 5-FU in the blood, as well as in the liver and tumorigenic tissue. Following FT-207 administration, the blood, tumor and liver tissue levels were lower than in the IVH group (oral administration). The liver 5-FU concentration, at 0.10 +/- 0.02 microgram/g, was significantly higher in the intravenous feeding group than in the p.o. group (0.05 +/- 0.01 micrograms/g). The 5-FU blood concentration rose quickly, reaching 0.051 +/- 0.013 micrograms/ml and 0.035 +/- 0.004 micrograms/ml at 9 and 12 hours, respectively, following treatment. This was significantly higher than in the p.o. group, which showed corresponding levels of 0.031 +/- 0.004 microgram/ml and 0.022 +/- 0.002 microgram/ml, respectively. The increase in the 5-FU level within the tumor was markedly high in the IVH group compared to the p.o. group, and it peaked at 9 hours following administration. The concentration in the IVH group was thus higher than in the p.o. group at any given time. At 24 hours after treatment, the IVH group level was 0.35 +/- 0.09 microgram/g, against 0.27 +/- 0.05 microgram/g in the p.o. group. The blood concentration of 5-FU following intravenous feeding maintained a high value for a long time, and the 5-FU tumor concentration also remained at a high level. The intravenous route was therefore considered to be advantageous for antitumor chemotherapy. PMID- 3099650 TI - [Evaluation of rIFN-gamma in the treatment of lymphoma and melanoma of the skin by systemic and intralesional administration]. AB - This study evaluated the clinical effect of rIFN-gamma for the treatment of lymphoma and melanoma of the skin by systemic intravenous and intralesional administration. By intravenous drip infusion, one of two cases of mycosis fungoides (stage IV) showed CR of skin lesions by administration of a total of 160 X 10(6) units, 4 or 8 X 10(6) units, every other day for 3 months. The remaining case was, however, in a state of PD. Intralesional administration of rIFN-gamma to six cases of cutaneous lymphoma, including three cases of mycosis fungoides, two cases of cutaneous T cell lymphoma, and one case of adult T cell lymphoma, resulted in three cases of CR, two cases of MR and one case of PD. In contrast, four cases of malignant melanoma, two of which received systemic administration and two intralesional administration, did not show any obvious clinical response, one showing PR and the other three PD. Histopathological examination of skin lesions before and after administration of rIFN-gamma indicated that the cutaneous lymphoma lesions were initially infiltrated by lymphocytes and macrophages, and that later on, they were free from tumor cells. Our study indicates that rIFN-gamma appears to provide a new modality for the treatment of cutaneous lymphoma by systemic and intralesional administration. PMID- 3099652 TI - [Enhancement of antitumor effect induced by ischemia in intraarterial chemotherapy (experimental study)]. PMID- 3099651 TI - [Evaluation of immunochemotherapy in patients with primary liver cancer. Osaka Research Society for Liver, Gallbladder and Pancreas]. AB - The effectiveness of BRM (biological response modifier) for primary liver cancer was investigated in a prospective randomized and well controlled study. The protocol consisted of 3 groups: 1) Tegafur oral administration only, 2) OK-432 i.v. plus Tegafur, and 3) PSK oral application plus Tegafur. One hundred seventy two Japanese patients were entered. The results revealed that BRM addition was more effective than Tegafur therapy alone with regard to tumor regression and the results of clinical examinations, but that there was no difference in subjective symptoms between the use of BRM and the other regimes. As to prognosis, patients given PSK survived longer than those given Tegafur alone, but OK-432 group had the same survival rate as the other two groups as a whole. The relationship among the three groups with regard to survival time, was similar to that of their respective total efficacies. Between the three groups, there was a significant difference in the incidence of adverse effects. The difference was sustained with the occurrence of fever symptoms as a result of OK-432 stimulation, with and BRM therapy decreased the gastro-intestinal side effects in comparison with the control group. PMID- 3099653 TI - [Effect of intravesical instillation of the antitumor chemotherapeutic agents mitomycin C and cytosine arabinoside on rat bladder carcinogenesis initiated by N butyl-N-(4-hydroxybutyl) nitrosamine]. AB - The effects of intravesical instillation of cytosine arabinoside (CA), mitomycin C (MMC) and combination of CA and MMC were examined in rats pretreated with N butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Rats were given initial treatment with BBN for 4 weeks followed by intravesical instillation of drugs once a week for 12 weeks. The total observation period was 36 weeks. Instillation of MMC markedly increased the development of bladder tumors, although CA did not. Moreover, tumor incidence in the combination group was less than that with MMC only. The results indicate that the intravesical instillation of MMC promotes 2 stage bladder carcinogenesis, whereas CA does not. Moreover, it is suggested that CA inhibits the promoting effect of MMC. PMID- 3099654 TI - Limitations of carbon dioxide lasers for treatment of port-wine stains. PMID- 3099655 TI - The case for use of the carbon dioxide laser in the treatment of port-wine stains. PMID- 3099658 TI - [Chemoprophylaxis with intravesical thiotepa in non-infiltrating bladder tumors]. PMID- 3099660 TI - Resumption of Schistosoma haematobium transmission after drought and subsequent flood. PMID- 3099659 TI - Screening methods for urinary schistosomiasis in an endemic area (the Kraboa/Coaltar district of Ghana). PMID- 3099657 TI - [A very large bladder diverticulum. Emergency echographic diagnosis]. PMID- 3099656 TI - [Urinary bilharziasis. Report of a new case]. PMID- 3099662 TI - Heart-lung transplantation: current status. PMID- 3099661 TI - Measurement of peak blood levels of oltipraz in patients infected with S. mansoni: correlation with the drug's antischistosomal action. PMID- 3099663 TI - Heart-lung transplantation: lessons learned and future hopes. AB - Since March, 1982, 33 patients have undergone cardiopulmonary transplantation. Nineteen were discharged from the hospital following the operation, and 16 continue to do well. Eight patients have survived 1 year, 5 patients 2 years, and 1 patient 3 years. Often survival has been influenced most by the selection of candidates, as no patient who had undergone a previous sternotomy survived (3 of 3). All 7 early (between 30 and 72 days) and 3 late (145 to 466 days) deaths were related to infection. Methods for ex vivo preservation of the heart-lung bloc have included storage at 4 degrees C, cardiopulmonary bypass and profound hypothermia, and autoperfusion of the heart-lung bloc. The last technique is original and currently is preferred for distant procurement. Because dehiscence of the tracheal anastomosis has occurred in 3 patients, a sutured line is now encircled with a wrap of omentum. Isolated rejection of the lung is frequent in the first three weeks following operation and has been controlled with methylprednisolone. Late survivors have shown a mild restrictive lung disorder that has not progressed between 6 and 24 months. Bronchoalveolar lavage has been useful for diagnosing infection and providing insight into the immunobiology of the transplanted lung. Although mortality and morbidity have been high, the experiences gained through this series will likely result in an improved outlook for future recipients. PMID- 3099665 TI - [Serodiagnosis of bilharziasis by indirect ELISA reaction]. PMID- 3099664 TI - Age and sex related differences in some rat renal NADPH-consuming detoxification enzymes. AB - Age- and sex-associated changes in some renal drug-metabolizing enzyme activities (NADPH-cytochrome c reductase, the glutathione peroxidase-glutathione reductase system, and thioredoxin reductase) were investigated using male and female Wistar rats (ages ranging from -4 days to 24 months). During aging the activities of NADPH-cytochrome c reductase and thioredoxin reductase showed a marked decrease (approximately 50% in both enzymes compared to adult stage). Glutathione reductase activity presented similar values in adulthood and aging, and glutathione peroxidase activity showed an increase with age (30% compared with the adult values). A marked sex difference was observed in young rats for glutathione peroxidase and thioredoxin reductase activities. However, during aging this difference disappears for glutathione peroxidase activity, but it remains for thioredoxin reductase activity (the specific activity in male old rats was approximately two-fold that obtained from female old rats). The variations in these enzymatic activities may be important when determining the changes in susceptibility of the kidneys to toxic chemicals with aging. PMID- 3099668 TI - Effects of natamycin and potassium sorbate on growth and aflatoxin production in olives. AB - Aspergillus flavus NRRL 6555 was inoculated onto whole olives and olive paste samples containing variable amounts of either natamycin or potassium sorbate and incubated at 15 degrees, 25 degrees, and 35 degrees C for 7, 14 and 21 days for whole olives and at 15 degrees and 25 degrees C for 8 and 16 days for olive pastes. The initiation time of growth was parallel to the concentrations of either preservatives applied. However, at 15 degrees C, natamycin at 160 and 320 micrograms/g (ppm) completely inhibited the growth of mold on whole olives for 21 days and olive paste for 7 and 15 days, respectively. All levels of potassium sorbate inhibited mold growth at 15 degrees C, but at 25 degrees C, 6000 micrograms/g (ppm) only, delayed growth for 15 days. The extent of growth at the end of the incubation periods was parallel to the temperatures of incubation. The analyses for aflatoxin B1 production in all samples at all levels of preservatives and control were negative. PMID- 3099666 TI - [Sero-epidemiological study of intestinal bilharziasis in Ampefy (Lake Itasy, Madagascar)]. PMID- 3099667 TI - [Serodiagnosis of bilharziasis caused by Schistosoma mansoni using the ELISA technic in Madagascar]. PMID- 3099669 TI - The influence of oral hypoglycaemic sulfonyl ureas on prostacyclin release by the rat thoracic aorta. AB - The influence of some oral hypoglycaemic sulfonyl ureas on PGI2 release by the rat thoracic aorta in vitro was examined using reversed phase HPLC. The column (Micro Pack MCH-10) (30 cm X 4 mm) was eluted using the solvent mixture:acetonitrile:glacial acetic acid:water (23:0.1:76.9v/v/v). Preincubation of the aortae with the sulfonyl ureas (15 microM) enhanced PGI2 release. The control release (measured as 6-oxo-PGF1 alpha) was 1.15 +/- 0.1 ng/mg wet weight. This was significantly increased to 2.30 +/- 0.20, 2.50 +/- 0.30, 2.90 +/- 0.25, 2.10 +/- 0.20 and 2.40 +/- 0.30 ng/mg by glibenclamide, gliclazide, acetohexamide, glibornuride and chlorpropamide, respectively (P less than 0.01, n = 6). Mepacrine (0.5 mM) abolished both basal and stimulated release. Thus, the enhanced PGI2 release may probably involve activation of the enzyme phospholipase A2. None of the compounds affected ADP-induced rat platelet aggregation even when the platelets were preincubated for 10 min at a concentration of 100-180 microM. The enhanced release of PGI2 may help to delay the development and progression of retinopathy, nephropathy, hypertension and thrombosis in diabetic patients prone to these diseases. Furthermore, the enhanced PGI2 release may partly underly some of the previously observed and poorly explained findings following the administration of some sulfonyl ureas into mammals. PMID- 3099673 TI - [Multicenter clinical trials: a pressing need for the development of new therapeutics]. PMID- 3099670 TI - Role of calcium in prolactin analgesia. AB - The effect of calcium chloride and nifedipine on prolactin-(PRL) induced analgesia was studied by chemical assay and compared with other analgesics like morphine, thyrotrophin-releasing hormone (TRH) and clonidine. Nifedipine potentiated the analgesic effect of PRL similar to morphine while that of clonidine and TRH remained unaltered. Further, calcium chloride administration antagonized the analgesic effect of PRL and of morphine. These data suggest that PRL, similar to morphine, may alter calcium movements across the membrane to produce analgesia. PMID- 3099671 TI - Reversal by L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a L-norepinephrine precursor of reserpine- or tetrabenazine-induced hypothermia. AB - The effects of L-threo-DOPS on the hypothermia and the decrease of brain norepinephrine (NE) concentration in the mouse pretreated with reserpine or tetrabenazine were studied. Reserpine (5 mg/kg, i.p.) or tetrabenazine (40 mg/kg, i.p.) produced a significant decrease in body temperature. The i.p. injection of L-threo-DOPS (100, 200 and 400 mg/kg) reversed these hypothermia in a dose dependent manner. These hypothermia were also antagonized by the i.c. injection of NE (5 micrograms/mouse). Both reserpine and tetrabenazine markedly decreased the brain content of NE, and L-threo-DOPS (400 mg/kg, i.p.) recovered it. These results suggested that L-threo-DOPS would reverse the reserpine- or tetrabenazine induced hypothermia at least in part by the formation of NE in the central nervous system. PMID- 3099672 TI - Role of the sympatho-adrenal system in the reflex tachycardia produced by hydralazine in the anesthetized rat. AB - The role of the sympatho-adrenal system in the production of tachycardia accompanying the hypotensive response to hydralazine was studied in urethane anesthetized rats subjected to previous bilateral adrenal demedullation or to pretreatment with 6-hydroxydopamine and compared with intact control animals. The prolonged hypotension induced by the vasodilator was not affected by these maneuvers, but the slowly developing tachycardia was reversed to bradycardia, which in the demedullated group was followed after 60 min by a moderate increase in heart rate. In the chemically sympathectomized rats, the cardiac depressant response was completely blocked by pretreatment with atropine. In additional experiments, previous administration of methylatropine enhanced hydralazine tachycardia, but atropine partially inhibited this response and changed its time course to mirror that of the hypotension. These results indicate that in urethane anesthetized rats, hydralazine tachycardia is mediated by sympatho-adrenal activation and that it is accompanied by a simultaneous heart rate-lowering parasympathetic discharge normally masked by the predominant tachycardia. They further suggest that the tachycardia is facilitated by a muscarinic mechanism which modulates central sympathetic influences on cardiovascular function. PMID- 3099674 TI - [Importance of magnetic resonance imaging in myocardial infarct]. AB - Imagery by magnetic resonance (IMR) represents a new modality of medical imagery based on the interaction between the magnetic fields produced by radio-frequency waves and living substance. IMR finds an interesting application in the study of different stages of myocardial infarction. In 30 cases of myocardial infarction IMR was compared with thallium tomoscintigraphy and echocardiography. In the acute stage, myomalacia appears in IMR as a superbrilliant zone, and in the chronic stage parietal thinning and dyskinesias are apparent. Intraventricular thromboses, but also hemostasis in aneurysmatic or akinetic sites are visualised as a high-intensity signal within these areas. IMR represents therefore a new means of evaluation of size and evolution of the necrosis. This procedure provides also functional informations about the contraction and flow anomalies. PMID- 3099676 TI - [Study of segmental ventricular contraction by the analysis of the radius of curvature]. AB - We have developed a procedure for segmental contraction analysis in the left ventricle based on the study of the radius of local curvature. This method has the advantage of non-necessitating the determination of basal reference values. The problem of optimal homogenisation of the raw date was resolved by developing a method based on a mobile average of 5 points by introducing a ponderation by second derivations. This method allows to describe various types of possible segmental contraction in ischemic cardiopathies and obstructive cardiomyopathies. Among the possible anomalies, inversion of the curvature radius has a particular importance (Laplace's law). If localized, it produces an increase in the parietal constraint with a possible extension of the ischemic process. If more extended, a pressure instability (CMO) ensues, independently of the parietal constraint developed. PMID- 3099677 TI - [Determining factors of the repetitive bursts in ventricular tachycardia]. AB - 24-h ECG recordings were studied in 60 patients suffering from salvos of repetitive ventricular tachycardia (VT), in order to determine the parameters affecting the repetitive response in ventricular arrhythmias. The tracings were analysed with the use of ATREC II system allowing the systematic study of 15 RR intervals and the heart rate in the 3 min preceding each type of event. The mean number of events taken into account per patient and per 24h of recording amounted to 673 +/- 521 for isolated ventricular extrasystoles, to 568 +/- 461 for paired ventricular extrasystoles and 435 +/- 810 for bursts of VT. The whole group was divided into two groups according to the absence (A) or presence (B) of associated cardiopathy. Group A included 30 patients with a mean age of 42 +/- 17 years, group B included 30 patients with a mean age of 42 +/- 17 years, group B included 30 patients with a mean age of 57.4 +/- 12 years. Three major factors responsible for the repetitive activity could be disclosed: The heart rate preceding isolated ventricular extrasystoles was lower than that preceding the salvos of VT (p less than 0.01) the duration of which increased in a linear way with the sinus rate; Duration of the cycle preceding the last sinus beat before the bursts (long duration in 77% in group A and in 57% in group B). In 60% of cases in group A and 40% in group B the coupling interval was all the more long as the response was repetitive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099675 TI - [Surgery of acquired heart valve diseases in France: developments in a 10-year period. A multicentric study]. AB - A multicenter study compares the surgery of acquired valvular diseases in France in 1974 and 1984. This study concerns etiology, surgical procedures and postoperative results within 3 months after operation. 2718 observations issued from 20 medical and surgical centers are divided in 2 groups: the first includes 856 patients who underwent surgical operation in 1974, the other group with 1862 patients was operated on in 1984. Significant differences may be observed. The mean age is higher in 1984 (55 vs. 47 years); the rheumatismal etiology decreases from 50.2% in 1974 to 35.1% in 1984; the degenerative and dystrophic causes increase from 13.8% in 1974 to 32.9% in 1984; while the monovalvular mitral lesion is more frequent (42%) than the aortic one (32.7%) in 1974, the proportion is reversed in 1984 where 47% aortic and 34.5% mitral lesions are found; the number of surgical treatments of mitral stenoses in 1984 is half of those in 1974, but the number of surgically treated aortic stenoses and mitral regurgitations is double of those in 1974; the preoperative examination includes left-side heart catheterization in 81.1% and coronary angiography in 64% of surgically treated patients en 1984, the respective percentages en 1974 being 57.8% and 16.1%. In 1974, 27.6% of patients are in a preoperative functional stage I or II, in contrast to 42.8% in 1984. Mitral commissurotomy represents 29.3% of mitral surgery in 1974 (25.6% of them with closed operation), the respective percentage in 1984 being only 10.5% (2.5% of them with closed heart operation).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099678 TI - [Evaluation of new pericardial bioprostheses by pulsed and continuous Doppler ultrasound ]. AB - The authors have studied by pulsed and continuous Doppler ultrasonography 108 pericardial prostheses in a good functional state implanted for less than five years to patients without any clinical and echographic signs of heart failure. The pulsed Doppler ultrasonography allowed to exclude the possible dysfunction of the prostheses; continuous Doppler ultrasonography allowed the measurement of the maximal transprosthetic velocities and to deduce the corresponding maximal and middle gradients by means of simplified Bernouilli's equation. Using three types of bioprostheses (Carpentier-Edwards, Ionescu and Mitroflow) the following problems were investigated: Normal ranges of maximal transprosthetic velocity and gradients. At the aortic level the maximal velocity ranges from 1.60 to 2.83 +/- 14 m/s and the maximal gradients from 10 for size 27-29 to 32 +/- 3.3 mmHg for size 19. At the mitral level the maximal velocity ranges from 0.80 to 2 m/s and the mean gradients from 1 for size 33 to 7 mmHg for size 25. The mean half-life of decrease is 100 +/- 28 ms. Thus all aortic bioprostheses appear to be stenosing, which is not the case for the mitral ones, size 31 and 33. Factors governing the maximal transprosthetic velocity and the gradients: these determining factors are the size, the type and the age of the bioprosthesis (r = 0.59 for the correlation between maximal velocity and size, r = 0.53 between size and mean aortic gradient). The accessory factors are the age and the functional condition of the myocardium. All these factors have to be considered and neutralized for allowing a valid comparison of various types of prostheses. Comparison of the three pericardial prostheses studied: in patients without signs of myocardial dysfunction of prosthetic origin and with comparable basal conditions, comparison of maximal velocity and of the gradient points to a significant superiority of the Mitroflow at the aortic level and of the Ionescu and Mitroflow at the mitral level. It should be noted in the end that the great similarity of the results obtained in the present study by Doppler ultrasonography with the previously reported hemodynamic data confirms the important role of the Doppler method in the evaluation of valvular bioprostheses. PMID- 3099679 TI - [Potential course of lesions of the ascending aorta in dystrophic aortic insufficiency]. AB - Dystrophic aortic insufficiencies represent at present time an important etiology of operated on pure and voluminous aortic regurgitations (n = 95, i.e. 28.1% of cases followed by our working team). The valvular dysplasic lesions by which they are characterized were associated in 2 out of 3 cases with parietal lesions of the ascending aorta: annulo-ectasic disease (n = 42) or important non-aneurysmal dilatation of the ascending aorta (n = 20). However, these valvular dysplasias may also appear isolated in an aorta morphologically normal at peroperative examination (n = 33). Among the 42 patients suffering from, annulo-ectasic disease (group 1) the type of surgical correction varied with the period of operation. Valvular replacement isolated (n = 3, group 1 a) or associated with aortic supracoronary surgery (n = 17, group 1b) were the procedures before 1978. Since then, 22 patients (group 1c) had a total replacement of the ascending aorta were subjected to valvular interventions (19 replacements, 1 valvuloplasty). When performed, parietal biopsy of the aorta showed in 11 out of 15 cases signs of cystic medio-necrosis. After a delay of 53 +/- 40 months, 11 out of 20 patients of group 1a and 1b died, 5 of them from the evolution of lesions at the ascending aorta (3 ruptures and 2 dissections); one patient was reoperated 12 years after the placing of a supracoronary tube, because of the development of a voluminous aneurysm of the sinuses of Valvalva which initially were only simply dilated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099680 TI - [Anti-Coxsackie antibodies and congestive cardiomyopathies]. AB - During a 4-years period 122 patients admitted to the cardiologic hospital in Lille presented a significative positivity of serological reaction against Coxsackievirus B. Among these patients 19 suffered from acute pericarditis, 4 from cardiac arrhythmias, 3 from Bornholm syndrome and 14 from apparently primary congestive cardiomyopathy. In most of these 14 patients representing 18.4% of congestive cardiomyopathies investigated at the same time, hemodynamic studies and heart scanning with radioactive gallium were performed. 7 of these patients had a chronic (group A) and 7 an acute evolution (group B). In group A the scans were negative 4 times out of 5, whereas in group B they were positive in 5 out of 5 examinations. The control group including 3247 patients coming from the Institut Pasteur exhibited serological positivity in 4.6% of cases. Comparison of this group with that of cardiomyopathies shows a significant difference (p less than 0.001). The authors draw the attention to the frequency of positive serodiagnosis in congestive cardiomyopathy and stress the importance of gallium scintiscanning. PMID- 3099681 TI - [Intraoperative evaluation of mitral valve reconstruction using two-dimensional contrast echocardiography]. AB - 20 patients who underwent reconstructive surgery for mitral regurgitation were peroperatively investigated by contrasted bidimensional echocardiography using intraventricular injection of 20 ml of physiologic saline. Before the valvuloplasty, the peroperative quantitation of mitral leakage was in all cases closely correlated with the data obtained preoperatively. After the mitral reparation, three groups of patients could be observed: group I (12 cases): absent or minimal regurgitation (0-+); group II (5 cases): moderate mitral regurgitation (++); group III (3 cases): marked regurgitation ( - +) necessitating an immediate ECC. In two cases it was possible to improve successfully the valvular function, in the third case valvular replacement was necessary. The correlation between the data of peroperative contrasted echography at one hand and the clinical examination and the postoperative paraclinical investigations on the other hand was excellent in all cases. Thus the contrasted bidimensional peroperative echocardiography represents a reliable method for predicting the immediate results of mitral reconstructive surgery. PMID- 3099682 TI - [Effects of nifedipine on carotid blood flow and baroreflex response in essential arterial hypertension. Preliminary results]. AB - The objective of this prospective study was to evaluate the effect of nifedipine administered at usual daily doses of 30 to 40 mg on the carotid flow in arterial hypertension. The study included 15 patients (8 men and 7 women), 50 to 79 (mean 59.5) years old suffering from long-standing, fixed essential hypertension becoming instable under central antihypertensive drug therapy. For calculating the carotid blood flow, vascular echotomography combined with Doppler ultrasonography and spectral analysis (Duplex probe) determining the vascular section and flow velocity were used. Arterial pressure using a mercury tonometer, flow velocity, common carotid artery diameter, carotid blood flow, Pourcelot's index, parietal tension and heart rate were measured before treatment and at the 8th day of nifedipine administration. It could be shown that the drug produced a significantly (p less than 0.001) increased carotid blood flow, in spite of a marked (p less than 0.001) decrease in systolic (p less than 0.001) and diastolic (p less than 0.005) blood pressure. The increase in carotid blood flow was directly related to the increase in flow velocity (p less than 0.001) and in the diameter of common carotid artery (p less than 0.01) and was associated with a significant decrease in the Pourcelot's index. Analysis of two groups of patients isolated from the total group according to the elevation of carotid blood flow, showed that the degree of hypotensive effect of nifedipine is negatively correlated with the baroreflex response determined by the variation of parietal tension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099683 TI - [Major tricuspid insufficiency and absence of systolic valvular coaptation. Echocardiographic study. Apropos of 6 cases]. AB - In a retrospective series of 960 cases of tricuspid regurgitation studied by two dimensional echocardiography 6 patients presented a systolic defect of valvular coaptation. The origin of this defect varied: one case was due to carcinoid, two to rheumatic cardiopathy, two to papyraceous right ventricle and one to sclerodermia associated with pulmonary arterial hypertension. The mechanism of the lacking coaptation varies according to the etiology: valvular retraction in carcinoid cardiopathy, right-ventricle dilatation, dilatation of the tricuspid ring and altered kinetics of the right ventricle in the other cases. Changed contractility of the right ventricle is the only element allowing to distinguish tricuspid regurgitation with and without a coaptation defect. Clinically this abnormality always points to an advanced stage of severe tricuspid regurgitation. PMID- 3099684 TI - [Injectable and oral propafenone in nodal reentry and pathways of ventricular preexcitation]. AB - Propafenone, an antiarrhythmic drug of IC type, was applied to 10 patients with supraventricular tachycardia (SVT) produced by intranodal reentry (group I) and in 14 patients with reentry by an accessory atrioventricular (AV) pathway (group II), 10 of them suffering from orthodromic SVT. Propafenone given intravenously depresses or blocks the antegrade or retrograde conduction in the AV node and in the accessory AV pathway. The same effect is observed with orally given propafenone: 66% of antegrade blocking and 54% of retrograde blocking of the accessory conduction pathway. Intravenously given propafenone reduces within 2 to 3 min by antegrade or retrograde blocking 70% of SVT produced by intranodal reentry and by 85% of SVT produced by reentry by the accessory pathway. After injection it becomes impossible to induce intranodal SVT in 60% of cases and SVT by the accessory pathway reentry in 28% of cases. With oral treatment (600 mg/day) reinduction of intranodal SVT becomes impossible in 66% of cases and of SVT produced by reentry by the accessory pathway in 42% of cases. Long-term oral administration (17 +/- 3.7 months) of the same dose prevents 88% of SVT produced by internodal reentry and 80% of spontaneous SVT produced by reentry by the accessory pathway. Cardiologic tolerance is satisfactory: one case of atrioventricular and intraventricular dysrhythmia is observed. The same holds true for general tolerance: in 2 cases drug administration is discontinued and 11 patients present neurologic and digestive troubles improving after lowering the dosage or increasing the fractionation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099685 TI - [Aneurysm of the sinistro-anterior sinus of Valsalva causing coronary insufficiency. Apropos of a case]. AB - The aneurysm of the sinistro-anterior sinus of Valsalva (ASASV) can very rarely be disclosed by symptoms of coronary insufficiency. The authors report the case of a 73 old man suffering from unstable angina pectoris, in whom the diagnosis of ASASV was evoked by two-dimensional echocardiography and confirmed by aortography. Coronary angiography revealed an external compression of IVA by the ASASV and allowed to exclude the presence of associated autonomous coronaropathy. The interest of this observation lies in the fact that the preoperative diagnosis was made after the two-dimensional echocardiography allowing the evaluation of the importance and volume of the ASASV. Aortography and coronary angiography are indispensable procedures in the presence of chest pain suspect of coronary insufficiency. These investigations will guide the surgical treatment which should always associate a closure of the aneurysmal neck, an aortic valvular replacement and a bypass of the compressed coronary artery. PMID- 3099686 TI - [Bilateral coronary-pulmonary fistula and tritruncal stenotic coronary atheroma. Apropos of a new case with review of the literature]. AB - In a 62 years old patient suffering from stenocardia and paroxysms of atrial fibrillation, coronary angiography disclosed two coronary-pulmonary fistulas associated with a tritruncal stenotic coronary atheroma. During the operation consisting of a double aortocoronary shunt and closing the anomalous pulmonary ostium, a control coronary angiography confirmed the shunt permeability and showed the absence of opacifications at the passage of the fistulas. In the immediate postoperative period the recurrence of paroxysmal atrial fibrillation was no longer accompanied by stenocardia which did not reappear one year after operation. This observation illustrates the fact that coronary-pulmonary fistulas may aggravate a fortuitously associated coronary insufficiency. PMID- 3099688 TI - [Arrhythmogenic effects of anti-arrhythmia agents]. PMID- 3099687 TI - [Delayed clinical course of right ventricular infarction. Importance of changed diastolic function]. AB - This observation illustrates once more the possibility of a delayed appearance of clinical manifestations of the infarction of the right ventricle. Morphological analysis during the catheterization provides a means for a detailed presentation of the adiastolic syndrome, stressing the importance of diastolic function of the right ventricle, especially the role of pericardium. The role of pericardial compliance seems to be brought into play by the acute dilatation of the right ventricle during its necrosis consecutive to the thrombosis of the right coronary artery at its genu superius. PMID- 3099689 TI - [Use of structured lights in the evaluation of thoracic deformity bound with cardiac activity. Study of apical impulse using Moire technics]. AB - Chest deformation due to cardiac activity can be studied with the use of techniques based on Moire principle. The shadow technique allows to obtain well contrasted fringes, whereas the technique of projected Moire allows an easier taking of camera pictures. The fringes in this case, although less contrasted, allow to recognize level differences of the order of 0.17 mm with a network of 20 traits/mm in the present configuration of our material. The best criteria of registration have been set up after the study of 10 young subjects. In the presented case topographic measurements allowed a quantitative evaluation of the apical impulse. The telesystolic image after treatment allowed a tridimensional reconstruction of chest deformation. PMID- 3099690 TI - [Seminars on arterial hypertension. Paris, 20-21 December 1985. Arterial Hypertension Section of the French Society of Cardiology]. PMID- 3099691 TI - [Course of renal function in malignant hypertension. Effect of treatment. Study of 30 cases followed for 5 to 18 years]. AB - Renal insufficiency is the most frequent complication of malignant hypertension (MHT). The initiation of effective hypotensive treatment is generally followed by a rapid improvement of renal functions, but the long-term evolution has been only rarely studied. A group of 30 patients was retrospectively selected on the following criteria: Malignant hypertension: mean DBP 138 +/- 20 mmHg, hypertensive retinopathy stage III-IV; Early renal insufficiency: mean Inulin clearance (CIN) 66 +/- 26 ml/min, mean PAH clearance (CPAH) 364 +/- 161 ml/min; Clinical and functional follow-up ranging from 5 to 18 years. Among these patients, two groups were defined according to the quality of BP control: good or fair responders (GR) with a DBP always less than 110 mmHg, poor responders (PR) with a DBP occasionally greater than or equal to 110 mmHg. The results show in the two groups an improvement of CIN at 3 years, followed by a stabilization then a decrease after the 6th year. However the early improvement is significantly lower in PR. Despite similar initial values (GR = 54.7 +/- 31.3; PR = 51.4 +/- 13.2), CIN remains always lower in PR (at 9 years = GR 72.4 +/- 30.6; PR 56.0 +/- 19.8). During the first 3 years, CPAH increases in GR, whereas it decreases in PR, resulting in significantly different values at 3 years. At 9 years, CPAH remains improved in GR (329.1 +/- 109.3 vs 281.7 +/- 173.8 initially) but decreased in PR (256.0 +/- 166.9 vs 307.3 +/- 119.5 initially). The parallel improvement of CIN and CPAH in GR confirms a favorable effect of BP control on early vascular lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099692 TI - [Primary microvascular lesions of the kidney or pre-hypertensive nephroangiosclerosis. 25 cases]. AB - Isolated non inflammatory lesions of renal microarteries (eventually with mild thickening of tubular basement membranes, but with negative immunofluorescent glomerular studies) were observed in 25 patients (22 males) in whom renal biopsy have been performed for proteinuria (P). Selection criteria were: pathological lesions by definition; absence of hypertension (HT) in clinical and at the time of biopsy; minimum follow up of 4 years after the first statement of the proteinuria (4 to 29 years; mean 14 years). Three groups have been isolated: 1. 3 patients have had an acute glomerulonephritis followed by disappearance of proteinuria. It reappears 1 to 5 years later. HT was discovered 2, 8 and 11 years after the proteinuria. Renal failure occurred 1 and 3 years after HT. 2. 14 patients had hereditary or acquired vascular risk factors (obesity, smoking, ethylism). In 7, HT occurred 3 to 15 years after P. In 2, renal failure occurred 4 to 8 years later. 3. 8 patients had no vascular risk factor; in 3 of them Ht developed 7, 13 and 20 years after the first statement. A positive immunofluorescence with IgM or C3 on renal arterioles had been found in only 3 of the 10 patients who in group 2 and 3 became hypertensive. A proteinuria may precede the occurrence of HT without being induced by glomerulonephritis. Group 2 and 3 suggest that these renal lesions of arterial sclerosis precede and may be a factor of HT. Indeed, this entity may be considered as a prehypertensive condition. PMID- 3099694 TI - [Essential thrombocythemia and hypertension as a result of stenosis of the renal artery]. AB - Primary thrombocythemia may cause vascular thrombosis; it has been rarely involved in coronary atherosclerosis with myocardial infarction. We report three cases of renal arteries atherosclerosis occurring in association with primary thrombocythemia. These cases are three young women (20, 40 and 42 years old) with severe hypertension secondary to atherosclerosis with stenosis of renal arteries, one or both sided, and in association in one case with diffuse arterial stenosis. Systematic investigation revealed thrombocytosis with latent myeloproliferative syndrome of megacaryocytic colony. Thrombocytosis was previously present as attested by a blood count one year before (in one case) and by long-term peripheral vasomotor troubles, electively improved by aspirin (in two cases). In none of these three cases, vascular risk factors, nor hereditary vascular diseases were present. So we assume that platelets high levels are responsible for this early atherosclerosis, in keeping with the well-know role of platelets in atherosclerosis pathogenesis. Platelets investigations must be done in case of renovascular hypertension, occurring without any classical vascular risk factors. PMID- 3099695 TI - [Psychological factors and blood pressure in children. Various results using Zazzo's Bestiary Test]. AB - The purpose of the study was to investigate the relationships between psychological characteristics and blood pressure. Through animal metaphor R. Zazzo's Bestiary test indicates the child's basic psychological position and his way of coping with his personal conflicts. The test was administered to 766 children between the ages of 4-10 years. The links between diastolic and systolic blood pressure values, and the children's responses to the test were established by several discriminant analyses. A correspondence-analysis threw light on the psychological meaning of these relationships by indicating in hypertensive children a tendency towards perceiving human relationships as aggressive, especially between males and females. PMID- 3099693 TI - [Microalbuminuria in diabetics with moderate hypertension]. AB - The relation between hypertension and diabetic nephropathy is complex. Nephropathy is probably involved in the elevated blood pressure found in diabetic patients. In maturity onset diabetes, patients may also have hypertension which is associated with obesity or essential hypertension. It has been suggested that in both types of diabetes, hypertension enhances the development of diabetic nephropathy. Moreover, an aggressive antihypertensive treatment seems able to reduce rate of decline in kidney function in insulin-dependent diabetic patients with patent nephropathy. In this work, creatinine clearance and microalbuminuria in 20 diabetic patients (mostly with maturity-onset-diabetes) with known moderate and effectively treated hypertension were therefore measured and the results were compared with those for 18 normotensive diabetic patients and 22 controls. Duration of diabetes was from one to 26 years (mean: 11 years) and duration of hypertension was from one to 35 years (mean: 10 years). Patients and controls had normal serum creatinine and proteinuria below 0.1 g/l. Microalbuminuria was measured by immunonephelometric assay using specific antiserum (sensitivity = 1.5 mg/l; intra and interassay coefficients: 6.5% and 8% respectively). The highest value was observed in hypertensive diabetic patients with retinopathy (group 1). But hypertensive patients without retinopathy (group 2) and normotensive patients also had significantly increased microalbuminuria. In group 1, microalbuminuria was significantly higher than in group 2. The creatinine clearance was reduced in groups 1 and 2 versus normotensive diabetics, but hypertensive patients were older.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099697 TI - [Urinary excretion of kallikrein and sensitivity of blood pressure to acute sodium loading in healthy subjects]. AB - Acute extracellular volume expansion (VE) by isotonic saline is associated with variable change in mean arterial pressure (MAP) in normotensive subjects (NT). Following VE by 1,800 ml isotonic saline in 3 h, two patterns of MAP response were observed in NT: either an increase by more than 10% (SS: sodium or VE sensitive, n = 12) or no change (NSS: non-sodium or VE sensitive, n = 14). We assessed in all subjects the response to VE of glomerular filtration rate (GFR), urinary sodium (UNaV) and kallikrein (UKalV) excretion rate, plasma renin activity (PRA) and aldosterone concentration (PAC). Family history of blood pressure was not different between the groups. In response to VE, MAP increased (88 +/- 3 to 102 +/- 4 mmHg) in group SS and did not change in group NSS (83 +/- 3 to 85 +/- 3 mmHg). Whilst UNaV measured during the hour prior to VE was similar in both groups, the total amount of sodium excreted during VE was higher in group SS than in group NSS (52 +/- 9 vs 32 +/- 3 mmol/3 h, p less than 0.05). Control GFR as well as changes in GFR associated with VE were similar in both groups. A similar decrease in PRA and PAC was observed in both groups and pre-VE values were identical. UKalV was lower in SS than NSS subjects during the pre-VE control jour (0.42 +/- 0.09 vs 0.74 nKat/h; p less than 0.05) and during VE (1.14 +/- 0.16 vs 2.5 vs 0.47 nKat/3 h; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099696 TI - [Testing an expert system for hypertension]. AB - An Expert System (ES) has been connected to a database management system for the management and follow-up of hypertensive patients. The patient data base, called Artemis, contains approximately 18,000 medical records. About 90% of the initial informations used by the ES is contained in the medical records of the Artemis data base. The knowledge base consists of 870 rules. A first group of rules allows the description of knowledge structures (hierachies, graphs and mutual exclusions). The second group consists of production rules which describe the dynamic reasoning of the expert. The inference engine uses a combination of forward and backward chaining. The ES produce diagnostic hypotheses (possible causes of hypertension) and therapeutic suggestions before and after requiring additional information (patient supplementary interrogation, biological or radiological investigations). The evaluation of the diagnostic performance of the ES was made on 40 confirmed cases of secondary hypertension (SH) and 40 cases of essential hypertension (EH). The initial initial diagnosis, just after the forward chaining step, was correct in 17 cases of SH and 32 cases of EH. The final diagnosis proposed after several steps of forward and backward chaining was correct in 37 cases (92%) of SH and 36 (90%) of EH. Averages of 5 (EH) and 8 (SH) questions were formulated by the ES to reach the final diagnosis. The integration of the ES to the database is expected to facilitate the validation of the knowledge base and to enhance its overall acceptability. Whether or not such an integration will be useful and accepted as a complementary tool by physicians remains however an open question. PMID- 3099698 TI - [Reduction of urinary kallikrein in hypertensive diabetics]. AB - Renal Kallikrein, an enzyme of the distal tubule acting through kinin liberation, may participate to the control of renal circulation and blood pressure. To study if an impairment of its secretion may exist in diabetics, a cross-sectional study was carried out on 40 non-hypertensive and 29 hypertensive diabetics, compared to 30-age related controls. Urinary Kallikrein Activity (UKA) was measured by its kininogenase activity with and without trypsin preincubation. Compared to UKA in controls (86 +/- 9 micrograms lysyl-bradykinin [LBK] produced per minute of incubation), UKA was significantly reduced either in non-hypertensive diabetics (59 +/- 8 micrograms LBK. min.-1; p less than 0.05) and in hypertensive diabetics (26 +/- 6 micrograms LBK. min.-1; p less than 0.001). The ratio of total/active urinary kallikrein was similar in diabetics and in controls. The decline of UKA in diabetics was related to the duration of their disease (r = -0.38; p less than 0.05) and to their stage of retinopathy (r = -0.46; p less than 0.001). UKA values were proportional to creatinine clearance in diabetics (r = 0.58; p less than 0.001). The lowest UKA values were found in patients with a high urinary excretion of albumin (above 500 mg/day): 8 +/- 2 micrograms LBK. min-1 (p less than 0.001) and beta-2-microglobulin (above 382 micrograms/day): 12 +/- 4 micrograms LBK. min-1 (p less than 0.001). These findings support that an impaired secretion of renal kallikrein in diabetics can be related to the duration of diabetes and to the severity of microangiopathy. PMID- 3099699 TI - [Plasma catecholamines, free and conjugated, in the hemodialyzed chronic renal failure patient]. AB - Free, sulfo and glucuro-conjugated catecholamines (dopamine, noradrenaline and adrenaline) were measured to study their metabolism in 35 non-selected patients with chronic renal failure, and under hemodialysis for various periods of time. Our data demonstrate a statistically significant increase of free dopamine, and free noradrenaline concentration in these patients, while that of free adrenaline was not different from controls. However a careful scrutiny of 35 individual data suggests that sub-groups of patients with either high normal or low plasma free noradrenaline concentration could exist; this likely heterogeneity could be a good explanation for conflicting conclusions provided by previous reports. Suspecting that conjugated catecholamines might be altered in these patients, plasma sulfo and glucuro-conjugated amines were measured. We have found a predictable and highly significant increase of sulfo-conjugated catecholamines; glucuroconjugated dopamine and noradrenaline were unchanged, while glucuroconjugated adrenaline was significantly increased. The physiological meaning, if any, of these new observations on conjugated catecholamines cannot be assessed at the moment. PMID- 3099700 TI - [Hypotensive effect of a human anti-renin monoclonal antibody (4G1D8) in the sodium-depleted alert marmoset]. AB - A dose-response relationship was involved after an intravenous bolus of a human antirenin monoclonal antibody (4G1D8), in sodium depleted marmosets. The sodium depletion (furosemide: 30 mg/kg/d for 2 days) was used to potentiate the contribution of the renin-angiotensin system in the blood pressure (BP) control. To record BP and inject the antibody, 2 catheters were implanted the day before the experiment. The plasma renin activity (PRA) was measured by the RIA of angiotensin I after an incubation of plasmas for 1 hour at pH 7.4. The sodium depletion induced a dramatic increase of PRA (63.68 +/- 20.03 ng/ml/h of angiotensin I compared to 2.96 +/- 1.03; p less than or equal to 0.01; n = 13). The basal BP was 102.6 +/- 2.4 mmHg (n = 17). The maximal fall in BP was noted at about 30 min for the three groups of animals treated by 4G1D8; it was -7.5 +/- 4.3 mmHg at the dose of 0.01 mg/kg (n = 4), -21.3 +/- 3.8 mmHg (p less than or equal to 0.01) at 0.10 mg/kg (n = 4), and -27.5 +/- 1.4 mmHg (p = 0.10) at 0.24 mg/kg (n = 4). At the 0.10 and 0.24 mg/kg doses, the hypotension was lasting (greater than 3 h). PRA was strongly inhibited and HR was little modified. A dose response relationship with a human antirenin monoclonal antibody, 4G1D8, provides a very interesting pharmacological model for a comparative study of renin inhibitors. PMID- 3099701 TI - [Normalization of active urinary kallikrein excretion by young spontaneously hypertensive rats by chronic inhibition of conversion enzyme]. AB - This study was designed to investigate the decreased urinary kallikrein excretion (Ukall.V) in Okamoto-Aoki spontaneously hypertensive rats (SHR) and the effect of long-term converting enzyme inhibition. From ages 4 to 7 weeks, Ukall.V was determined (amidolytic assay: nanokatals/wk) in 4 groups of 6 male rats housed into individual metabolic cages and fed a normal sodium diet: SHR and normotensive Wistar-Kyoto rats (WKY); SHR-C and WKY-C which were given captopril: 30 mg/kg BW every 12 hours by gavage. Ukall.V was each time lower in SHR than in age-matched WKY, even at 4 wks of age (54.6 +/- 9.1 vs 108.5 +/- 16.1 nkat/wk; p less than .01) when systolic blood pressure (s.BP) was already higher. In SHR-C, s.BP was identical or slightly lower to that in WKY. Ukall.V was still lower at wk 4 when captopril was first administered (60.9 +/- 8.4 nkat/wk; p less than .01), but identical to that in WKY at each subsequent age (105.7 +/- 25.9 vs 114.1 +/- 5.6 nkat/wk at wk 5; 219.8 +/- 44.5 vs 253.4 +/- 22.4 nkat/wk at wk 7). Excretion of active kallikrein was highly correlated to s.BP in WKY (r = .87), SHR (r = 0.91) and SHR-C (r = 0.95). The slope of the regression line relating Ukall.V with s.BP was significantly less in SHR than WKY (1.33 +/- 0.35 vs 3.36 +/- 0.84 nkat/wk/mmHg; p less than .01); the slope in SHR-C (3.35 +/- 0.77 nkat/wk/mmHg) was significantly steeper than in SHR (p less than .01) and identical to that in WKY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099702 TI - [Urinary excretion of thromboxane B2 in the genetically hypertensive rat of the Lyons strain]. AB - In order to assess the pathophysiological role of the renal Thromboxane (Tx)A2 in genetic hypertension, the urinary excretion of its stable metabolite: the TxB2 was followed in groups of 12 hypertensive (LH), normotensive (LN) and low blood pressure (LL) female rats of the Lyon strains at the ages of 5, 9, 21 and 32 weeks. In the 3 strains studied, the urinary TxB2 excretion markedly decreased between 5 and 9 weeks of age and did change thereafter. In addition, 5 and 9 weeks old rats exhibited an increased urinary TxB2 output compared to LN and LL controls. Since TxA2 is a potent vasoconstrictor, it seems likely to hypothesize that the early increase observed in the renal TxA2 biosynthesis could be one of the primary events occurring during the development of hypertension in this rat model. PMID- 3099703 TI - [Dietary magnesium and mineralocorticoid DOCA-salt hypertension in the rat. Effect on the metabolism of sodium and magnesium]. AB - The effects of a diet enriched in magnesium were studied in mineralocorticoid DOCA-salt hypertensive rats from 6 to 15 weeks old, during the development of hypertension. A standard normomagnesic diet with 0.21% Mg and 0.24% Na, equilibrated in minerals and vitamins is used as a control diet. The high magnesium diet is the same standard diet enriched in magnesium with a content of 0.75% Mg. That in magnesium enriched diet lessens the level of blood pressure. This effect appears within 2 weeks and is long lasting. Increase of urinary sodium is observed but without any modification of sodium balance. Sodium plasma is not changed. Plasma, urinary and balance of magnesium are increased. These results establish that in mineralocorticoid DOCA-salt hypertension, a high magnesium diet decreases hypertension. The observed metabolic variations may perhaps explain the protective effect of this in magnesium enriched diet. PMID- 3099706 TI - [Predictability of post-captopril acute renal failure in hypertension with renal artery stenosis of a single kidney or bilateral stenosis]. AB - Use of converting-enzyme inhibitors in patients with hypertension and bilateral renal artery stenosis or renal artery stenosis in a single kidney may be complicated by acute renal failure (ARF). The aim of this work was to find a simple test to predict this accident. PAH clearance (CPAH), Inuline clearance (CIn) and Glomerular Filtration Fraction (GFF) were measured before and three hours after a single oral dose of Captopril (50 mg) in 7 hypertensive patients (sodium intake = 6 g/24 h). All these patients presented significant stenosis (greater than 60%) of the artery of a transplanted kidney (5), of a single kidney (1) or a bilateral renal artery stenosis (1). During the following three days, 50 mg captopril was given twice a day. ARF with creatinine serum level higher than 300 mumoles/l was seen in 4 patients (Group II); in 3 patients (Group I) creatinine serum level didn't change. Values measured before the single dose of captopril and variations after three hours are reported in the table: (Table: see text). Before captopril, in Group II CPAH and CIn are lower and GFF is higher, but these is not significant difference between the two groups. After Captopril CIn and GFF are significantly decreased in Group II (29.1 and 36.6% vs 7.8 and 10%). These results allow two conclusions: 1) Basal values of Glomerular Filtration Rate plasma flow and filtration fraction are not predictive parameters for acute renal failure after captopril therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099707 TI - [Hypertension and stenosis of the graft artery: effects of conversion enzyme inhibition]. AB - The use of angiotensin converting enzyme inhibitors may lead to reversible renal insufficiency in transplant patients with transplant renal artery stenosis (TRAS). We assessed acute effects of captopril (50 mg, p. os) in 7 cadaver kidney recipients (mean age: 35.6 +/- 4 yrs) with TRAS, 9 to 46 mo after transplantation. All patients were treated by prednisolone and azathioprine. After captopril administration, mean arterial pressure decreased from 127 +/- 6 to 119 +/- 7 mmHg, effective renal plasma flow from 152 +/- 19 to 118 +/- 19 ml/min/1.73 m2, glomerular filtration rate from 59 +/- 8 to 39 +/- 10 ml/min/1.73 m2 and filtration fraction from 0.39 +/- 0.02 to 0.32 +/- 0.07. Among the 7 patients, 2 developed immediate and transient anuria; 4 presented a net decrease of GFR, only one had stable GFR. This patient was chronically treated by captopril; as BP was not controlled, furosemide (40 mg p. os) was added. Serum creatinine increased from 180 to 250 mumol/l. Percutaneous angioplasty was done without decrease in BP; however, treatment by captopril and furosemide could be reinstitued without deterioration in renal function. We conclude that: acute renal failure in kidney graft recipients with TRAS is frequent, but not mandatory; sodium depletion induced by diuretics enhances the fall in GFR; acute effect of captopril must be assessed in patients with TRAS before the use of this product as long term antihypertensive treatment. PMID- 3099710 TI - [Ambulatory recording of blood pressure. Study of the reproducibility of findings in 25 subjects]. AB - The reproducibility of a novel ambulatory blood pressure (B.P.) monitoring was tested, for clinical trial in hypertension. The spacelabs apparatus is based on standard auscultatory and oscillometric blood pressure measurements. Ten normotensive patients and 15 hypertensive patients were investigated as follows: their blood pressure was monitored twice over a 24 hr period at an interval of 30 and 15 days respectively. The monitoring data were expressed as the mean of the average blood pressure over day-time (7 hr-22 hr) and 24 hr as well as 24 hr. B.P. profiles (means of 4 measurements per hour). The statistical analysis of the two subpopulations of patients showed a satisfaction reproducibility of both the 24 hr B.P. curves (normotensive patients: PAS: r = 0.94; PAD: r = 0.92; Hypertensive patients PAS: r = 0.82; PAD: r = 0.64 p less than 0.001). and blood pressure levels (normotensive patients: J1: 113 +/- 10/70 +/- 6 mmHg; J30: 110 +/ 10/68 +/- 6 mmHg. Hypertensive patients: J1: 150 +/- 10/98 +/- 9 mmHg; J15: 155 +/- 15/96 +/- 8 mmHg). In contrast, analyzing each patient individually exhibited a correct reproducibility of the B.P. levels but the 24 hr--profiles of either the diastolic or systolic blood pressure could not be correlated with sufficient reliability (normotensive patients: 7 times out of 10 for PAS, and 4 times out of 10 for PAD; hypertensive patients: 5 times out of 15 for PAS, and 3 times out of 15 for PAD). In addition, the patient activity, should be carefully controlled during ambulatory blood pressure measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099711 TI - [Reduced sensitivity to noradrenaline and electric stimulation of the caudal artery of the aged rat]. AB - Whilst arterial noradrenaline (NOR) content decreases with age (Waterson, et al. 1974; Neubauer and Christensen, 1978; Embree, et al., 1981), changes in vasoconstriction induced by NOR are equivocal (Tuttle, 1966; Cohen and Berkowitz, 1976; Scott and Reid, 1982; Duckles, et al., 1985). We have investigated changes in responsiveness to NOR in the NOR-rich rat tail artery. Two cm segments of the proximal tail artery from male Ivanos rats of 6/7, 16/17 or 30/31 months were perfused/superfused with Krebs bicarbonate (4 ml/min). Changes in perfusion pressure (mmHg) were determined after (1) electrical stimulation (1 to 30 Hz, 0.3 msec, 15 sec at supramaximal voltage, ES) followed by (2) perfusion with exogenous NOR (1 nM to 10 microM for 2 min at each concentration). Responses to ES were abolished by pretreatment with reserpine (2.5 mg/kg, i.p. at - 18 h) or perfusion with phentolamine (4 microM). They were produced therefore, by liberation of endogenous NOR. Arterial NOR content was determined by HPLC-EC following perchloric acid digestion (0.1 N). RESULTS: (Table: see text). Asterisks refer to t-test with 6/7 months age group (p less than 0.05, p less than 0.01 and p less than 0.001]. There were no differences in basal perfusion pressure before stimulation or in plateaux responses to maximal concentrations of NOR. In conclusion our results show a decrease in arterial NOR and in sensitivity to both endogenous and exogenous NOR with age. PMID- 3099705 TI - [Normalization of renin secretion by neuropeptide Y in adrenalectomized rats with glucocorticoid-induced hypertension]. AB - In the periphery, neuropeptide Y is present in the circulation, in the adrenal medulla as well as at the level of nerve endings and of the juxtaglomerular apparatus. The aim of the present study was to assess the effect of this neuropeptide on renin secretion. Normotensive rats were biadrenalectomized or sham-operated and made hypertensive with methylprednisolone acetate (20 mg/kg s.c. once weekly). Deoxycorticosterone pivalate (10 mg/kg s.c. once weekly) was also given to prevent mineralocorticoid deficiency. Two weeks after that initial surgery 12 adrenalectomized rats and 8 sham-operated rats were infused for 30 min with neuropeptide Y (0.1 microgram/min) whereas 8 adrenalectomized rats and 9 sham-operated rats received in similar conditions the vehicle of neuropeptide Y (10 microliters/min). At that time, the rats were conscious and there was no significant difference in blood pressure and heart rate between the 4 groups of rats. At the end of the experiment, adrenalectomized rats exhibited a markedly stimulated renin-angiotensin system. Neuropeptide Y made it possible to normalize plasma renin activity in these rats, thus suggesting that neuropeptide Y plays an important role in regulating renin secretion. PMID- 3099704 TI - [Canrenone: an effective antihypertensive in an experimental model of hypertension in which the active transport of sodium is diminished]. AB - Recent studies in essential hypertensive patients and rats with genetic hypertension strongly suggested that the development of primary hypertension results from a transient and chronic "cascade" of events; I) excess Na+ intake, II) secretion of natriuretic factors, III) abnormal cell Na+ homeostasis in the vascular wall, due to the presence of inherited and induced abnormalities in different Na+ transport system and IV) increase in cytosolic free Ca2+ content and sympathetic drive. In vitro studies have previously shown that canrenone, an antihypertensive antialdosterone drug, behaves like a partial agonist at the digitalis-receptor site of the Na+, K+-pump. In particular, it has been shown that canrenone counterbalances the increases in internal Na+ and cytosolic free Ca2+ contents induced by ouabain in cultured smooth muscle cells. We thus investigated the effect of canrenone administration in a model of experimental hypertension with increased endogenous "ouabain-like" factors (rats with reduced renal mass under excess Na+ intake: RRM-salt rats). Results presented here confirm that RRM-salt rats exhibit: volume expansion, strongly decreased plasma renin activity, increased endogenous "ouabain-like" factors and (IV) decreased Na+, K+-pump activity and increased Na+ content in erythrocytes. In addition, we found that canrenone is antihypertensive in this model and this is associated with a tendency to normalize volume expansion, plasma levels of endogenous "ouabain-like" factors, Na+, K+-pump activity and Na+ content in erythrocytes. In conclusion, our results suggest that administration of canrenone to RRM-salt rats may induce a lowering of blood pressure by antagonism with endogenous "ouabain like" factors at the vascular wall. PMID- 3099717 TI - [The Lyons Hypertension Control Program (1972-1978). Community analysis]. AB - A Community Control Program of Hypertension was undertaken in Lyon, as part of a WHO program. It dealed with two occupational, Study (S) and Reference (R), communities, each amounting to about 12,500 subjects. Its goal was to improve the level of treatment of hypertension in S, by stimulating the usual health care system without modifying it. It began in 1972 by a baseline total survey of both communities. Its aim was to check that the percentage of treated hypertensive subjects (HT) was the same in S and R (respectively 10.9% and 11.7%, n.s.), and to detect all HT's (subject being given an antihypertensive drug treatment, and/or BP greater than or equal to 160 and/or 94, or greater than or equal to 150 and/or 90 before age 30). The S intervention involved: detection of "new HT's" during the whole program; information of HT's, and referral to the treating physician of their choice, who was informed about the aim of the program and received later periodic information about hypertension management; periodic follow-up reconvocations. A leaflet including advices for C-V prevention was distributed to the whole S community in 1976. Evaluation was performed by a terminal total survey of both communities, from 1977 to 6/1978 (examination rates: 94.4 and 91.6% in S and R). The evaluation involved two analysis of 1977 data. -Cohort analysis (reported before): the percentage of treated HT's in the cohorts of 1972 HT's, still present in the community and hypertensive, was higher in S (63.0) than in R (46.1) (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099715 TI - [Sports and blood pressure: association in a population of wage-earners]. AB - In a cross-sectional epidemiological survey, we examined the association between the practice of sports and blood pressure (BP). The study included 3,388 male employees (representing 90.1% of the target population) who were questioned about their habitual sports activity, in terms of average duration per week and intensity. The proportion of subjects who stated to engage in sports activity decreased with age, from 50.9% in the age class 20-29 years to 16.4% in the age class 50-59 years. We found a negative relationship between both systolic and diastolic BP and the weekly duration of sports activity. However this association increased with age and reached the statistical significance only in the age classes 40-49 years and 50-59 years (p less than 0.01 and p less than 0.001, respectively). Similar results were obtained when intensity of sports was used instead of duration. In order to test the independence of the observed association, the duration of sports activity (hours/week) was included as an independent variable in a multiple linear regression analysis, along with the following potential confounders: age, Quetelet index, alcohol consumption, cigarette smoking, heart rate, and level of education. In this analysis the sports-BP relationship was considerably attenuated or entirely disappeared. It remained statistically significant only in the age class 50-59 (p less than 0.01 for systolic BP an p less than 0.05 for diastolic BP). Our results support those of others showing a modest beneficial effect of leisure time physical exercise on BP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099713 TI - [Effects of aldosterone and vasopressin on transmembrane efflux of sodium from the arterial wall]. AB - We have previously shown that, injected s.c. to adrenalectomized Sprague-Dawley rats (SD.ADx), aldosterone has a mineralocorticoid specific effect on transmembrane movements of 22Na from arterial smooth muscle. These effects appear to be partly due to the action of an humoral factor. Indeed, in vitro, the late increase in passive 22Na efflux is not observed (Moura and Worcel, 1984). In rats perfused with a specific antagonists of the pressor effect of vasopressin (Vp), the in vivo administration of aldosterone induced a kinetic action similar to that observed after in vitro exposure to the mineralocorticoid. These results suggested that Vp may be the humoral factor (Moura, Angeli and Worcel, 1985). In adrenalectomized homozygous Brattleboro rats (DI.ADx), aldosterone (10(-8)M) increases ouabain independent 22Na efflux (DI.AX: 0.073 +/- 0.002 min-1(n = 15); DI.ADx + Aldo: 0.096 +/- 0.002 min-1(n = 12)p less than 0.01) and ouabain dependent 22Na efflux (DI.ADx: 0.031 +/- 0.001 min-1; DI.ADx + Aldo: 0.037 +/- 0.002 min-1 p less than 0.01). Vp also increases ouabain sensitive and insensitive 22Na effluxes and potentiates the effects of aldosterone on passive Na+ transferts (DI.ADx + Aldo + Vp: 0.015 +/- 0.003 min-1 (n = 16) p less than 0.01). In conclusion, these results suggest that Vp may be involved in the effects of aldosterone on 22Na effluxes. Furthermore Vp potentiates the effects of aldosterone on passive 22Na effluxes. But it is not yet possible to ascertain if Vp action is additive or permissive. PMID- 3099709 TI - [Comparison of ambulatory blood pressure determinations using the Remler and Spacelabs devices]. AB - Ambulatory blood pressure recorded with the Spacelabs was compared with both Remler recordings and office blood pressures in 11 normotensive and 13 hypertensive volunteers. Analysis of 324 simultaneous measurements with Remler and Spacelabs showed very high correlation for systolic and for diastolic blood pressure. For systolic blood pressure, measurements with Spacelabs recorder were lower than those with the Remler recorder by a mean of 3.6 +/- 6.5 mmHg, principally in hypertensive subjects. Spacelabs measurements were also lower than Remler measurements for diastolic blood pressure by a mean of 5.3 +/- 6.6 mmHg principally in normotensive subjects. The averages of blood pressure variability (standard deviation as index) recorded by each device were identical. Mean systolic and diastolic blood pressure differed by more than 10 and 5 mmHg respectively between the two devices in 11 and 83% of the subjects. These individual discrepancies were unpredictable. Comparison of Spacelabs records with office blood pressure measured with a standard mercury manometer showed discrepancies of more than 10 mmHg for systolic blood pressure and more than 5 mmHg for diastolic blood pressure in 46 and 42% of the 24 subjects, respectively. These discrepancies could be due, in part, to different methods of blood pressure measurements. These data demonstrate that the Spacelabs apparatus provides records for a group, reasonably close to those obtained with the Remler over a wide range of blood pressure. For the management of hypertension, the advantages- as compared to physician's measurements--of ambulatory blood pressures recorded with indirect methods,need to be weighed, taking into consideration the difference between the ambulatory record and the office blood pressure measured with the same device. PMID- 3099718 TI - [Acebutolol and cerebral blood flow of the moderately hypertensive aged subject]. AB - In 17 moderate hypertensive patients (mean age = 67 +/- 8.8) the effects of a chronic oral administration of the beta blocking agent acebutolol on regional cerebral blood flow (rCBF) was studied using the non invasive 133 Xenon inhalation technique. The results was compared to the rCBF obtained in an age matched normal control group. Our study shows that during long term therapy low doses of acebutolol (200 mg/daily) the rCBF is unaffected by a decrease (20 mmHg) of the mean arterial blood pressure. The relative hypofrontality of the elderly hypertensive patients leads to be corrected by acebutolol. PMID- 3099714 TI - [Non-invasive study of the role of carotid distension in the baroreflex response to the arteriolar vasodilator cadralazine in essential hypertension]. AB - Using pulsed Doppler methods, hemodynamics of the common carotid and the brachial arteries were measured in 10 patients with essential hypertension. After vasodilatation due to Cadralazine, a Dihydralazine-like substance, mean arterial pressure significantly decreased and heart rate increased. Change in PRA was significantly and positively correlated with the change in heart rate. In the brachial artery circulation, diameter and vascular resistance decreased while blood flow velocity and volumic blood flow did not increase significantly. In the common carotid artery circulation, diameter, mean blood flow did not change. However, vascular resistance and tangential tension decreased slightly. The increase in heart rate was strongly and negatively correlated (r = 0.82 p less than 0.01) with the change in the carotid artery tangential tension (measured as the product between mean arterial pressure and arterial radius) while no comparable correlation was observed with the change in blood pressure or arterial radius alone. The study suggested that in essential hypertensives, modifications in the carotid artery tangential tension secondary to arteriolar vasodilatation contribute actively to the baroreflex response. PMID- 3099708 TI - [Can ambulatory blood pressure be assessed using 9 self-measurements?]. AB - This study compares the blood pressure (BP) levels, the variability and the circadian BP variation recorded in ambulatory (AM) and self measurement (SM) conditions. The BP is recorded every 15 min on the day time with an automatic device (Space-labs) in a population of 16 normotensive patients; the same day, each patient performs with an half automatic device (SEB) 9 self measurements between 8 am and 8 pm. The SM method provides significantly lower mean values: 3.9 mmHg and -3.1 mmHg for the Systolic and the Diastolic blood pressure (SBP and DBP) than the AM. The heart rate (HR) also is lower in SM than in AM (-6.5 cy/min). The BP variability is lower for the SBP and the HR in SM. The correlation between AM and SM hours means is poor. This study shows that the self measurement method provides a lower BP level and variability than the full ambulatory method and the hourly means variation are not assessed. PMID- 3099719 TI - [Comparison of MIBG scintigraphy and computerized tomography in the localization of pheochromocytomas]. AB - Ninety-nine patients suspected of having pheochromocytoma were studied with MIBG scintigraphy and in 92 of them were studied with computed tomography. In 49 patients, the diagnosis was ruled out, in 3 patients it remained doubtful, and in 47 patients it was confirmed. Two patients had epinephrine--and/or norepinephrine -non-secreting tumors and 45 had secreting pheochromocytomas. In these latter patients, there were 4 scintigraphic false-negatives, all intra-adrenal, and 4 computed tomography false-negatives, 3 extra-adrenal and 1 intra-adrenal. For about 80% of the patients and/or the tumor sites, both methods were thus in agreement. They were complementary in the remaining 20%. The advantage of scintigraphy is to screen the whole body with high specificity and to locate extra-adrenal sites or metastases of pheochromocytoma with better accuracy than computed tomography. The limits of scintigraphy are the possibility of false negatives in around 10% of patients whereas computed tomography visualizes more than 95% of intra-adrenal tumors. PMID- 3099716 TI - [Alcohol consumption and treatment of hypertension. Results of an occupational medicine survey]. AB - The results of a cross-sectional study were analysed in order to assess the therapeutic control of hypertension in relation to alcohol consumption. 6,665 subjects, employed in small and medium-sized companies of the Paris region were examined in a cross sectionnal study. Among the 1,008 hypertensive subjects, awareness of hypertension decreased with increasing alcohol consumption, from 72% among the 304 non-drinkers to 59% among the 201 heavy drinkers (six glasses/day and more) (p less than 0.05). Similarly, the percentage of subjects under current antihypertensive medication on the day of examination was lower in heavy drinkers, 19%, than among tetotalers, 42% (p less than 0.001). An antihypertensive treatment had been prescribed to 510 subjects. Among them, compliance, as stated by the interview, decreased with increasing alcohol consumption, from 70% to 34% (p less than 0.001). Using a logistic regression, the adjusted relative risk of non-compliance among heavy drinkers (6 glasses/day or more) was found to be 1.9. Among the 344 subjects under antihypertensive treatment on the day of examination, systolic and diastolic blood pressure were higher among heavy drinkers, 167/102 mmHg, than among teetotallers, 154/95 mmHg (p less than 0.01 both). The relative hypertension awareness, treatment and control status was thus poorer among, moderate and heavy drinkers than among the light and non-drinkers (table I). (Table: see text). The importance of the problem of alcoholism is thus emphasized, in both the fields of hypertension prevalence and control. PMID- 3099724 TI - Effectiveness of treatment of children with hypogammaglobulinemia: comparison of fresh plasma and intravenous immunoglobulin preparation. AB - Eight children aged 2 to 16 years who were diagnosed as having primary humoral immunodeficiency were treated with fresh plasma substitution, during the first 2 years. Subsequently these children and 5 other children with primary humoral immunodeficiency (ID) were treated during the next 10 months with intravenous preparation of IgG. Eight children received doses of 500 mg/kg body weight (group A), while five children received doses of 150 mg/kg (group B) at monthly intervals. After five months of this therapy the average increase of IgG concentration was in group A--395 mg/dl, while in group B--100 mg/dl, the difference being statistically significant. Substitution therapy with intravenous IgG was more effective than therapy with fresh plasma and caused appreciable clinical improvement. Only in one out of 130 cases of intravenous injections mild post-transfusion reaction was observed. PMID- 3099721 TI - [Continuous enteral nutrition in the treatment of infants with "travelers' diarrhea" and severe malnutrition]. AB - A prospective study of children aged 2-22 mos with traveller's diarrhea and severe malnutrition (weight loss greater than or equal to 10%; mean 17.8%) treated with a standardized progressive semi-elemental drip feeding (Alfare and Dextrine-maltose) after rehydration was undertaken. In 18 children, this therapy was successful and duration of the hospital stay was 15.7 days. In 6 other children, relapse was treated with the same protocol with success and duration of the hospital stay was 29 days. Total parenteral nutrition was unnecessary. Evolution of serum prealbumin and anthropometric parameters was good. PMID- 3099728 TI - Presidential address. Alas in Wonderland! PMID- 3099726 TI - Malignant mesotheliomas with osseous and cartilaginous differentiation. AB - This report describes ten examples of diffuse pleural tumors felt to represent malignant mesotheliomas with osseous and cartilaginous differentiation. Typically, the patients involved were elderly whites who presented with chest pain, bloody pleural effusions, and diffuse and nodular pleural disease on chest roentgenograms. An asbestos-exposure history was indicated in six of the ten patients. Seven cases were malignant fibrous mesotheliomas, and three were biphasic mesotheliomas. Results of immunoperoxidase studies for cytoplasmic keratin were positive in three of six cases of malignant fibrous mesothelioma. PMID- 3099722 TI - [Facial dysmorphism related to valproic acid ingestion during pregnancy]. AB - The authors report a case of cranio-facial changes in a neonate who had been exposed to Valproate. Clinical picture consisted of hypoplastic fronto-orbital edges and microstomia. These abnormalities are compared with the series reported in the literature. PMID- 3099725 TI - Sheep serum complement sensitisation of sheep erythrocyte-rabbit antibody complexes for haemolysis by guinea-pig complement plus EDTA or Mg2+-EGTA. AB - Sheep erythrocyte (E)-rabbit antibody (A) complexes incubated with sheep serum diluted up to 1:5120 or 1:20480 and washed can be haemolysed by guinea-pig (g-p) serum (complement, C) containing EDTA or Mg2+-EGTA respectively as haemolytic finishing reagents. Sheep E carrying a high dose of rabbit A were necessary for this reaction, particularly with g-p C-EDTA. G-p serum (stored by freezing) was active as a haemolytic finishing reagent with both EDTA and Mg2+-EGTA. Reconstituted freeze-dried g-p serum (also stored by freezing) was haemolytically active with Mg2+-EGTA only. G-p serum preserved by Richardson's method did not function as a finishing reagent with EDTA or Mg2+-EGTA. A non-haemolytic prozone occurred with sheep E-rabbit A treated with dilutions of sheep serum or body fluid up to 1:160, particularly when g-p C (frozen)-EDTA was used as the finishing reagent. Sheep E-rabbit A were sensitized by serum, foetal lamb serum, pericardiac-, synovial- or ovarian follicle-fluids colostrum or milk for haemolysis by g-p C (frozen)-EDTA or -Mg2+-EGTA. With the C3 inhibitors cobra venom factor or salicylaldoxime, serum sensitisation of sheep E-rabbit A for haemolysis by g-p C (frozen)-EDTA or -Mg2+-EGTA was not blocked. Sensitisation by serum heated at 50 degrees C for 30 min (partial inactivation of C2) was incomplete. Inhibitors of C1 (antrypol, chelators of Ca2+ or heating serum at 56 degrees C for 30 min) partially or fully blocked sensitisation for haemolysis by both g-p C (frozen)-EDTA or -Mg2+-EGTA. These results show that at a minimum, components C1, C4 and C2 are present and functionally active in serum and some body fluids of sheep. PMID- 3099712 TI - [Effect of inhibition of angiotensin converting enzyme on hypertension following kidney transplantation]. AB - The activation of the renin angiotensin system is thought to be an important factor contributing to hypertension following kidney transplantation (TX). We studied 21 hypertensive renal transplant recipients, without evidence of acute graft rejection or transplant artery stenosis, 6 to 60 months post-TX. The acute responses of mean arterial pressure (MAP) and renal hemodynamics (ERPF: effective renal plasma flow, 131I-Hippuran clearance) and function (GFR: glomerular filtration rate, creatinine clearance; UNaV: urinary sodium excretion rate) to converting enzyme inhibition (CEI) by captopril were assessed. CEI induced a decrease in MAP (118 +/- 2 to 110 +/- 2 mmHg), renal resistance (RR: 0.27 +/- 0.02 to 0.21 +/- 0.01) and filtration fraction (FF: 0.31 +/- 0.02 to 0.23 +/- 0.01). ERPF (307 +/- 24 to 333 +/- 18 ml/min/1.73 m2) and GFR (88 +/- 5 to 78 +/- 5 ml/min/1.73 m2) were not significantly changed. UNaV increased by 53 +/- 24 mumol/min. Changes in MAP (r = -0.66), ERPF (r = 0.74) and FF (r = -0.88) were significantly correlated with the log of control plasma renin activity (PRA). In 10 patients with an increase of ERPF (range: + 30 to + 70%) and no change in GFR, the activated renin system could originate from the recipient's own kidneys. In the remaining 11 patients, CEI was associated with no increase in ERPF (change: + 2 to - 27%) and a fall in GFR, a response suggesting a possible intrarenal vascular damage. These results indicate that RAS participates in the regulation of systemic and renal vascular tone, with a possible predominant effect on efferent glomerular arteriole. PMID- 3099729 TI - Electron microscopical visualization of presumptive bacterial conjugation channel. Preliminary note. PMID- 3099731 TI - [15N transamination in the administration of various tracer substances. 1. Whole body studies in rats]. AB - 4 groups of 3 growing Wistar rats each were orally given either 15N methionine, 15N lysine, 15N glycine or 15N ammonia sulphate over 10 days. By means of measuring 15N, the 15N accumulation in the amino acids (AA) of the body protein, statements were to be made on the transamination of the individual 15N substances and thus their suitability as tracer substances for studies of N metabolism. None of the tested 15N AA achieved a proportionate labelling of all AA of the body protein. The AA used as tracer in each case showed the highest 15N labelling of all AA in the body. Of the amino 15N detected in the animal body, ca. 19% were found in Met after a 15N Met application, ca. 88% in Lys after a 15N Lys application and ca. 50% in Gly after a 15N Gly application. After the application of 15N ammonia sulphate ca. 42% of the body amino 15N are apportioned to the essential and ca. 58% to the non-essential AA. Thus this substance produces a more proportional labelling of the essential and non-essential AA of the body protein than 15N Gly. The following quotas of the 15N amounts applied were found in the AA of the animal bodies: tracer substance lysine 52%, glycine 32%, ammonia sulphate 24%, methionine 21%. After summing up the amino acid 15N amounts in the animal body, eliminating in each case the tracer AA and taking into account the molecular weight of the AA, there was a good agreement of the intensity of the accumulation of 15N in the individual AA, irrespective of the applied tracer substance: arginine, glutamic acid, cysteine and aspartic acid highest, threonine, phenylalanine and lysine lowest accumulation. PMID- 3099732 TI - Efficiency of food utilization by pregnant and lactating sows. 2. The influence of isocaloric diets with different protein levels on pregnancy and lactation. AB - The efficiency of utilization of feed energy as digestible, metabolizable and net energy is similar in pregnant and lactating sows irrespective of the stage of these physiological conditions. This efficiency with the value of about 71% resembles the one found in the growing and fattening pigs, which enables us to use, for this category of animals, the same system offered evaluation and of the energy requirements based on fat nutritive units. The maintenance energy requirement expressed in ME varies from 467 kJ/kg 0.75 in pregnant sows to 512 kJ/kg 0.75 in lactating sows, for the suckling piglets having intermediary value of 498 kJ/kg 0.75. The efficiency of utilization of diets protein for maintenance and for synthesis is also similar for these categories of pigs, varying from 71% in lactating sows to 75-76% in pregnant sows. In suckling piglets we had recorded an efficiency of DCP utilization which varies parabolically with size of the ingesta and therefore with that of weight gain. The DCP maintenance requirement expressed in g N dig./kg 0.75 varies within narrow limits between 0.345 g N in suckling piglets 0.380 g N in pregnant sows; In lactating sows we have detected an intermediary value of 0.355 g N. Based on these experimental data and also using recent experimental results obtained by Schiemann and Beyer (1984) regarding the energy and N content of the foetuses, of the organs of reproductions and of milk, we could calculate the energy and protein requirements. These requirements when compared with the values used in our country show us higher values of energy in pregnant and lactating sows and lower values of protein for the same categories, including the piglets, where we have also found lower values for the energy too. PMID- 3099720 TI - Biosynthesis regulation of the beta-glucosidase produced by a yeast strain transformed by genetic engineering. AB - The biosynthesis of the beta-glucosidase enzyme was studied in a transformed yeast obtained by cloning in Saccharomyces cerevisiae the structural gene coding for beta-glucosidase in Kluyveromyces fragilis. The enzyme biosynthesis was found to be non-adaptative, and repressed by glucose. These features are similar to those observed in K. fragilis. beta-Glucosidase activity in the transformed yeast was much higher than in K. fragilis. We attempted to ferment cellobiose with the transformed yeast: practically no cellobiose was consumed, growth and ethanol production were negligible. Warburg experiments showed that cellobiose fermentation did not occur when the respiratory chain was not functioning. PMID- 3099733 TI - [The role of arachidonic acid metabolites on bronchial hyperresponsiveness to acetylcholine in asthmatic patients]. PMID- 3099723 TI - [Chylous ascites in infants]. AB - In a one month-old boy apparently idiopathic chylous ascites recovered with enteral feedings of an elementary diet excluding long-chain triglycerides. The authors emphasize the usual idiopathic character of chylous ascites in very young infants; the little interest of invasive investigations at such an age when data suggesting etiology are lacking; the interest of a trial of a non-invasive medical treatment, such as the one reported. PMID- 3099735 TI - [Cerebrovascular disorders in Uberlandia: II. Epidemiology and clinic medicine]. AB - We have studied prospectively 157 patients with stroke admitted at University Hospital and Hospital Santa Genoveva in Uberlandia, Brazil at the point of view of clinics and epidemiology. Incidence was 0.8/1000 peoples/year and early letality of stroke victims was 40%, only 30% had returned to work. Complete infarct account for 36.3% of the cases and was predominant in white man among stroke population. Hypertension (in 55% of the cases), Chagas' disease (26.1%), transient isquemic attack (22.7%) and hypercolesterolemia were the main risk factors for stroke in this region. PMID- 3099739 TI - Cholecystitis and bronchopneumonia associated with Pseudomonas aeruginosa in a koala. PMID- 3099740 TI - Application of an enzyme-linked immunosorbent assay in the final stages of a bovine brucellosis eradication program. AB - Bovine field serums from the Australian brucellosis eradication program were used to compare 2 enzyme linked immunosorbent assays (ELISA) with the complement fixation test (CFT) and Rose Bengal test (RBT). One ELISA used an anti-bovine IgG horseradish peroxidase conjugate (ELISA 1) and the other a monoclonal anti-bovine Ig alkaline phosphatase conjugate (ELISA 2). When compared with the CFT, the ELISA 2 like the ELISA 1 lacked specificity in B. abortus vaccinated herds but the ELISA 2 was more specific than the ELISA 1 in previously infected herds and equally as specific as the ELISA 1 in nonvaccinated Brucella free herds. In this study the ELISA 2 proved more sensitive than the CFT, RBT and ELISA 1 particularly in herds where B. abortus biotype 2 was present. The value of using the ELISA 2 in conjunction with the CFT in an eradication program is discussed. PMID- 3099727 TI - Biclonal gammopathy (IgG kappa and IgG lambda) in a patient with non-Hodgkin's lymphoma. PMID- 3099738 TI - 'No statistically significant difference'. So what? PMID- 3099741 TI - The prevalence and intensity of Sarcocystis spp infections in sheep. AB - A total of 864 sheep sold for slaughter throughout South Australia were examined for infections with Sarcocystis spp using macroscopic, microscopic and immunoserological methods of detection. Macroscopic cysts were found in 6.7% of the sheep ranging in intensity from 1 to 64 cysts per carcase. Morphometric studies detected 2 types of macroscopic cysts which differed in their size and cyst wall morphology. Large ovoid cysts with thick primary cyst walls were identified as S. gigantea (syn. S. ovifelis) whereas small slender cysts with thin cyst walls were identified as S. medusiformis. The prevalence of each species was 4.5% and 3.1% respectively. In comparison, microscopic cysts were detected in 93.2% of the sheep and stereological calculations of the intensities of infection ranged from 20 to 32,700 cysts per unit volume of muscle. Two types of microscopic cysts were also identified by differences in their cyst wall morphology. Cysts with smooth thin walls were detected in 88.1% of the sheep whereas cysts with radially-striated thick walls were found in 74.7%. Although these 2 types appeared to conform to the original descriptions of S. tenella and S. ovicanis respectively, both were classified as S. tenella (syn. S. ovicanis) pending further taxonomic studies. Specific antibody was detected in 93.7% of the sheep by the complement fixation test and in 96.9% by the indirect fluorescent antibody test (IFAT). A positive correlation was also found between the prevalence of IFAT antibody and the prevalence of infections by microscopic cysts. PMID- 3099742 TI - Effects of hypoxia and hyperoxia on ventilatory kinetics during recovery from exercise. AB - The purpose of this investigation was to determine the effects of breathing hyperoxic and hypoxic gas mixtures on ventilatory kinetics in the transition from submaximal exercise to rest. Eight male subjects performed three separate single blind exercise tests at 80% of their ventilatory threshold. Inspired oxygen concentration was varied in each experimental condition: test one (55% O2 -45% N2), test two (14% O2 -76% N2), and test three (21% O2 -79% N2). Ventilation, heart rate, and gas exchange were measured every 15 s for 6 min of exercise and during 9 min of recovery from exercise. Data analysis revealed no significant (p less than 0.05) differences in the kinetics of heart rate, oxygen uptake, expired volume of carbon dioxide, or ventilation among treatments during the transition from exercise to rest. Given the belief that hyperoxia attentuates the carotid bodies and hypoxia augments carotid body chemosensitivity, these findings suggest that the carotid bodies are not important regulators of VE kinetics during recovery from exercise. PMID- 3099730 TI - Comparison of quantitative microbiology and histopathology in divided burn-wound biopsy specimens. AB - We examined the association between quantitative microbiologic results and histopathologic findings in divided biopsy specimens from 200 burned patients. Microbiologic counts were determined as log10 colony-forming units per gram of disrupted tissue. Histopathologic results were scored on a scale of 1 to 6, values of 4 or greater indicating microbial invasion of viable tissue. Agreement of 96.1% was found between negative cultures, arbitrarily identified as those with fewer than 5 logs/g, and histologic absence of invasive infection. In sharp contrast, however, histologic invasion occurred in only 36% of specimens with positive cultures. Though low tissue counts are essentially synonymous with negative histologic findings, quantitative microbiology is not a diagnostic substitute for histologic examination, since high tissue counts quite commonly do not indicate invasion. The principal value of quantitative burn-wound biopsies is the demonstration of predominant burn-wound flora. PMID- 3099743 TI - Prevalence of penicillinase-producing Neisseria gonorrheae in Korea. AB - An almost two-fold increase in the monthly reported case rate for sexually transmitted disease (STD) in U.S. military members assigned in the Republic of Korea in April 1981 prompted an epidemiologic assessment of that population. Inasmuch as previously nonexistent treatment failures for Neisseria gonorrheae were also being reported, a demographic slice of 253 symptomatic military members was surveyed in June and July, 1981, for gonorrhea prevalence and the proportion of this that could be attributed to penicillinase-producing Neisseria gonorrheae (PPNG). Using standard and accepted methods, the gonorrhea prevalence rate in symptomatic military members was found to be 100% while the proportion that could be attributed to PPNG was 43%. In order to compare this to the contact population of local prostitutes, 116 asymptomatic women who presented to local STD clinics for routine, often legally-mandated examinations, were surveyed. The expected lower gonorrhea prevalence rate was 13.9% but the proportion attributed to PPNG was 27.6%. This data was similar to the sudden increase in PPNG experienced by U.S. military forces at Subic Bay in the Philippines in 1979 and reflected the slow but steady migration of this resistance throughout Asia. The long-accepted norm for gonorrhea treatment using penicillin was changed to spectinomycin in the U.S. military population and was being considered for implementation by the Korean official health community. Further organism resistance can be expected, and close monitoring is taking place. PMID- 3099737 TI - Extended-wear lenses, biofilm, and bacterial adhesion. AB - While medical scientific knowledge pertaining to bacterial adhesion to biomaterials has become a rapidly growing field in most areas of medicine, its significance in ophthalmic infections has not been emphasized. Corneal bacterial ulceration in patients wearing extended-wear contact lenses has become a problem of epidemic proportions. The designation of the contact lens itself as a suitable substratum for bacterial colonization and as a source of subsequent inoculum to compromised epithelial cells are important factors in the pathophysiology of corneal ulcer formation. We demonstrate polysaccharide- (biofilm-)mediated adhesion to two ophthalmic pathogens (Pseudomonas aeruginosa and Staphylococcus epidermidis) to the surface of a typical extended-wear contact lens in vitro using cytochemistry and scanning and transmission electron microscopic techniques. This interaction between the biomaterial and bacterial organisms, which represents a favorable self-protective environment for propagation and inoculation, is a previously overlooked area of importance in the mechanism of corneal ulceration associated with hydrophilic (soft) contact lenses. PMID- 3099744 TI - sn-Glycerol-3-phosphate oxidase and alcohol tolerance in Drosophila melanogaster larvae. AB - The role of sn-glycerol-3-phosphate oxidase (GPO; EC 1.1.99.5) in the variation of ethanol tolerance in Drosophila melanogaster was assessed in isofemale lines derived from individuals collected at the Chateau Tahbilk Winery and Wandin North Orchard of Victoria, Australia. When fed an undefined medium (semolina-treacle) with 6% ethanol (v/v), larvae of lines with high GPO activities survived better than did larvae of lines with low GPO activities. Although GPO was induced to higher activity levels by dietary ethanol in larvae of all the test lines, GPO activity was greater in lines representing the area outside the wine cellar. This implied that the cellar environment selected against individuals with high levels of GPO. These data do not explain the established difference in tolerance between cellar and outside populations. The GPO activities of lines were not dependent upon the activities of the lipogenic enzyme, glycerol-3-phosphate dehydrogenase; the major ethanol-degrading enzyme, alcohol dehydrogenase; or the citric acid cycle enzyme, fumarase. Thus, GPO activity is an important component of the metabolic mechanism of ethanol tolerance in larvae, but the mode of action of GPO has not been defined. PMID- 3099745 TI - The effect of temperature on biochemical and molecular properties of Drosophila alcohol dehydrogenase. AB - The gene products of the two major alleles of alcohol dehydrogenase (ADH-F and ADH-S) have been subjected to kinetic and biochemical analyses over a range of temperatures. Although temperature was found to have a significant effect on both kinetic and biochemical properties of Drosophila ADH, no significant differential effect was observed between the major ADH allozymes. The results are discussed within the context of the selective maintenance of Adh polymorphism in natural populations. PMID- 3099734 TI - [Peripheral polyneuropathy induced by benzonidazole in the treatment of Chagas' disease]. AB - Neurophysiological examination before and after the administration of benzonidazole, has shown peripheral polyneuropathy induced by this drug in most of the patients treated for chronic Chagas' disease. The polyneuropathy was mostly axonal and it was dose dependent being more severe in patients who had denervation of skeletal muscles before receiving the drug. PMID- 3099746 TI - The partial characterization of alcohol dehydrogenase null alleles from natural populations of Drosophila melanogaster. AB - Twenty-three alcohol dehydrogenase (ADH) putative null alleles extracted from four Tasmanian (Australia) populations of Drosophila melanogaster produce no ADH activity and are unable to form active heterodimers with either AdhF or AdhS. Twelve of these nulls were tested by enzyme-linked immunosorbent assay (ELISA) and did not produce any ADH cross-reacting material (CRM). The null homozygotes had similar, but slightly lower, mortalities on ethanol-supplemented media compared to an artificially induced null allele. Heterozygotes between the null alleles and standard AdhF and AdhS alleles had intermediate ADH activity and CRM levels. PMID- 3099749 TI - Competition of glycerol with other oxidizable substrates in rat brain. AB - The rate of conversion of [1,3-14C]glycerol into 14CO2 was measured in the presence and absence of unlabelled alternative substrates in whole homogenates from the brains of young (4-6 and 18-20 days old) and adult rats. Unlabelled glucose decreased 14CO2 production from [1,3-14C]glycerol by about 40% at all ages studied. Unlabelled 3-hydroxybutyrate significantly decreased the 14CO2 production from both low (0.2 mM) and high (2.0 mM) concentrations of glycerol in 4-6- and 18-20-day-old rat pups. However, the addition of 3-hydroxybutyrate had no effect on the rate of 14CO2 production from 2.0 mM-glycerol in adult rats, suggesting that the interaction of 3-hydroxybutyrate with glycerol in adult rat brain is complex and may be related to the biphasic kinetics previously reported for glycerol oxidation. Unlabelled glutamine decreased the production of 14CO2 by brain homogenates from 18-20-day-old and adult rats, but not in 4-6-day-old rat pups. In the converse situation, the addition of unlabelled glycerol to whole brain homogenates had little effect on the rate of 14CO2 production from [6 14C]glucose, 3-hydroxy[3-14C]butyrate and [U-14C]glutamine, although some significant differences were noted. Collectively these results suggest that glycerol and these other substrates may be metabolized in separate subcellular compartments in brain such that the products of glucose, 3-hydroxybutyrate and glutamine metabolism can dilute the oxidation of glycerol, but the converse cannot occur. The data also demonstrate that there are complex age-related changes in the interaction of glycerol with 3-hydroxybutyrate and glutamine. The fact that glycerol oxidation was only partially suppressed by the addition of 1-5 mM-glucose, -3-hydroxybutyrate or -glutamine could also suggest that glycerol may be selectively utilized as an energy substrate in some discrete brain region. PMID- 3099748 TI - Increased mouse epidermal ornithine decarboxylase activity by the tumour promoter 12-O-tetradecanoylphorbol 13-acetate involves increased amounts of both enzyme protein and messenger RNA. AB - Evidence was sought that the tumour promoter 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced mouse epidermal ornithine decarboxylase (ODC, EC 4.1.1.17) activity involves both increased ODC mRNA and ODC protein. Application of 10 nmol of TPA to mouse skin led to a dramatic increase in soluble epidermal ODC activity which paralleled an increase in amount of enzymically active ODC protein as determined by gel electrophoresis of immunoprecipitated difluoromethyl[3H]ornithine-bound ODC. Application of TPA to mouse skin also resulted in an increase in ODC mRNA measured by dot-blot analysis using a radiolabelled cDNA probe. ODC mRNA induction preceded the increase in ODC activity by TPA. TPA-increased ODC mRNA displayed a single major band of 2.1 kilobases in size identified by the Northern blotting procedure. PMID- 3099736 TI - Immunohistochemical localization of carbonic anhydrase in submandibular salivary glands of mice and hamsters treated with phenylephrine, testosterone or duct ligation. AB - Using the peroxidase antiperoxidase (PAP) technique, the submandibular glands (SMG) from normal mice showed positive carbonic anhydrase (CA) staining in both striated duct (SD) and granular convoluted tubule (GCT) cells, which varied from moderate to strong. In normal hamsters, the GCT showed strong focal staining. Phenylephrine in mice and hamsters resulted in a decrease in CA in GCT cells; staining was much reduced in the GCT segments of the mouse. One hour after a phenylephrine injection into testosterone-treated mice, there was no change in the staining intensity of GCT cells but an increase in cell size. Only a slight decrease in immunostaining occurred in mouse and hamster SD cells. CA staining in duct-ligated glands of mice decreased within 3 days but regenerated duct-like structures at later stages showed moderate staining. PMID- 3099747 TI - Mechanism of hepatic glycogen synthase inactivation induced by Ca2+-mobilizing hormones. Studies using phospholipase C and phorbol myristate acetate. AB - Incubation of hepatocytes with the protein kinase C activator and tumour promoter 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) produced a time- and concentration-dependent inactivation of glycogen synthase, but no change in phosphorylase. The same rate and extent of inactivation occurred in hepatocytes depleted of Ca2+ by treatment with the Ca2+ chelator EGTA. When hepatocytes were treated with the Ca2+-mobilizing hormone vasopressin (10 nM), the rate of glycogen synthase inactivation was similar to that observed with PMA (1 microM). Depletion of intracellular Ca2+ stores with EGTA abolished the ability of vasopressin to mobilize Ca2+ and activate phosphorylase without abolishing its ability to inactivate glycogen synthase and increase 1,2-diacylglycerol (DAG), the endogenous activator of protein kinase C. Protein kinase C, either in membranes or after partial purification, was shown to be activated in vitro by PMA in the presence of very low concentrations of Ca2+. Exogenous phospholipase C from Clostridium perfringens, at low concentrations, inactivated glycogen synthase and increased DAG without affecting cell Ca2+ or phosphorylase. It is proposed that the inactivation of glycogen synthase elicited by the Ca2+ mobilizing hormones is due, at least in part, to generation of DAG and activation of protein kinase C. PMID- 3099750 TI - Biosynthesis of complement C1 inhibitor by Hep G2 cells. Reactivity of different glycosylated forms of the inhibitor with C1s. AB - The biosynthesis of C1 Inh (C1 inhibitor) was studied in a human hepatoma cell line (Hep G2) by metabolic labelling, immunoprecipitation with anti-(C1 Inh) serum, analysis on SDS/polyacrylamide gel slabs and fluorography. Two forms of C1 Inh are secreted by Hep G2: a minor form of Mr 90,000 and a major form of Mr approximately 100,000. The latter form is also found in small amounts intracellularly in co-existence with an 80,000-Mr form. Accumulation of the 80,000-Mr C1 Inh is favoured when the cells are labelled at 23 degrees C instead of 37 degrees C or when they are treated with monensin. In the presence of tunicamycin, a compound that blocks the formation of N-asparagine-linked oligosaccharide chains, a decrease in Mr of both secreted and intracellular major forms is observed, indicating that secreted and intracellular C1 Inh contain N linked oligosaccharide units. The 100,000 Mr secreted C1 Inh is sensitive to endoglycosidase F but resistant to endoglycosidase H, and it incorporates [3H]galactose, [3H]glucosamine and [3H]galactosamine, indicating the presence of both N-linked oligosaccharides of the complex type and O-linked oligosaccharides. The intracellular C1 Inh contains N-linked oligosaccharide units of the high mannose type as demonstrated by endoglycosidase H-sensitivity. The functional activity of C1 Inh during its biosynthesis was tested by studying its reactivity towards C1s. Both secreted and intracellular C1 Inh form covalent-like complexes with purified plasma C1s. The underglycosylated C1 Inh secreted in presence of tunicamycin is still reactive with purified C1s. These results clearly show that sugars are not essential for this inhibitory activity of C1 Inh. PMID- 3099752 TI - Characterization of a high-Mr plasma-membrane-bound protein and assessment of its role as a constituent of hyaluronate synthase complex. AB - A high-Mr phosphoprotein (Mr 442,000) was purified from Nonidet-P-40-solubilized plasma membranes of cultured human skin fibroblasts. The protein comprised one 200,000-Mr subunit consisting of 116,000- and 84,000-Mr polypeptides and two identical 121,000-Mr subunits each consisting of 66,000- and 55,000-Mr polypeptides. The 200,000-Mr subunit and its polypeptides contained phosphotyrosine residues and were also [32P]phosphorylated at these residues from [gamma-32P]ATP in vitro by an intrinsic tyrosine kinase activity of the protein molecule in response to the presence of hyaluronate precursors, UDP-glucuronic acid and UDP-N-acetylglucosamine. The 121,000-Mr subunits and their polypeptides contained phosphoserine residues that could not be [32P]phosphorylated during autophosphorylation of the protein in vitro. The protein molecules separated from exponential- and stationary-growth-phase cells were identical in their quaternary structure, but appeared to exist in different proportions with respect to the state of phosphorylation of their 121,000-Mr subunits during different growth phases of the cell. Phosphorylation of polypeptides appeared to predispose in favour of their UDP-glucuronic acid- and UDP-N-acetylglucosamine-binding activities. The phosphorylated 116,000- and 84,000-Mr polypeptides of 200,000-Mr subunits possessed a single binding site for UDP-glucuronic acid and UDP-N acetylglucosamine respectively. The phosphorylated 200,000-Mr subunit could also cleave the UDP moiety from UDP-glucuronic acid and UDP-N-acetylglucosamine precursors. The phosphorylated 121,000-Mr subunit possessed two binding sites with equal affinity towards UDP-glucuronic acid and UDP-N-acetylglucosamine but did not possess UDP-moiety-cleavage activity. The phosphorylation of 200,000-Mr subunit by an intrinsic kinase activity of the protein molecule appeared to elicit its oligosaccharide-synthesizing activity, whereas phosphorylation of 121,000-Mr subunits, presumably carried out in vivo, abolished this activity of the protein molecule. The oligosaccharides synthesized by the protein were about Mr 5000 and about 12 disaccharide units in length. Neither nucleotide sugars nor glycosyl residues nor newly synthesized oligosaccharides were bound covalently to the protein molecule. The UDP moiety of nucleotide sugar precursors did not constitute a link between protein molecule and oligosaccharide during its synthesis. Although isolated 442,000-Mr protein did not synthesize high-Mr hyaluronate in vitro, this protein molecule can be considered as a constituent of membrane-bound hyaluronate synthase complex because of its observed properties. PMID- 3099754 TI - The purification and characterization of glucokinase from the thermophile Bacillus stearothermophilus. AB - Homogeneous glucokinase (EC 2.7.1.2) from the thermophile Bacillus stearothermophilus was isolated on the large scale by using four major steps: precipitation of extraneous material at pH 5.5, ion-exchange chromatography on DEAE-Sepharose, pseudo-affinity chromatography on Procion Brown H-3R-Sepharose 4B and gel filtration on Ultrogel AcA 34. The purified enzyme had a specific activity of about 330 units/mg of protein and was shown to exist as a dimer of subunit Mr 33,000. Kinetic parameters for the enzyme were determined with a variety of substrates. The glucokinase was highly specific for alpha-D-glucose, and the only other sugar substrate utilized was N-acetyl-alpha-D-glucosamine. The enzyme shows Michaelis-Menten kinetics, with a Km value of 150 microM for alpha-D glucose. The glucokinase was maximally active at pH 9.0. PMID- 3099753 TI - A lectin-binding glycoprotein of Mr 135,000 associated with basal keratinocytes in pig epidermis. AB - Pig epidermis separated by 1 M-CaCl2 treatment was homogenized and separated into three fractions by filtration through nylon mesh and high-speed centrifugation. Lectin-binding glycoproteins were isolated from urea/deoxycholate/mercaptoethanol extracts of the residue fraction that resisted filtration, from deoxycholate extracts of the particulate material in the filtrate and from the soluble fraction. Concanavalin A, Ricinus communis (castor bean) agglutinin 1, peanut (Arachis hypogaea) agglutinin and Ulex europaeus (gorse) agglutinin-binding glycoproteins in the three epidermal fractions were analysed by SDS/polyacrylamide-gel electrophoresis. A major neuraminidase-sensitive glycoprotein component of the particulate fraction of Mr 135,000 was strongly bound by concanavalin A and Ricinus communis agglutinin 1, but only weakly by peanut and Ulex europaeus agglutinins. This glycoprotein was not detected in the residue or soluble fractions of the epidermis, indicating that it had only a limited distribution within the tissue. The 135,000-Mr glycoprotein was one of two major glycoprotein antigens in the particulate fraction. Rabbits immunized with total particulate glycoproteins produced antibodies directed mainly against 135,000- and 110,000-Mr components. Monospecific antibodies were obtained from guinea pigs immunized with the 135,000-Mr glycoprotein band excised from polyacrylamide gels. Indirect immunofluorescence with the use of affinity purified antibodies showed that the 135,000-Mr glycoprotein was present at the surface of cells in the basal layer of the epidermis as well as at that of other stratified epithelia. It was not present on differentiating cells in the suprabasal layers of the epithelium, suggesting an important role in the attachment or proliferative functions of basal cells in stratified epithelia. Metabolic labelling studies with skin explants cultured in the presence of D [3H]glucosamine showed that this basal-cell glycoprotein was synthesized by cultured tissue. The major D-[3H]glucosamine-labelled glycoprotein component in the residue and particulate fractions of cultured epidermis had an Mr of 135,000, was immunoprecipitated by rabbit antisera raised against particulate epidermal glycoproteins and was bound by concanavalin A. The labelling of this glycoprotein with D-[3H]glucosamine was sensitive to tunicamycin, indicating that the basal cell glycoprotein contained N-glycosidically linked oligosaccharides. PMID- 3099751 TI - Analysis of cell-growth-phase-related variations in hyaluronate synthase activity of isolated plasma-membrane fractions of cultured human skin fibroblasts. AB - Hyaluronate synthase activity is localized exclusively in plasma-membrane fractions of cultured human skin fibroblasts. The enzyme activity of plasma membranes prepared from exponential-growth-phase cells was about 6.5 times that of stationary-growth-phase cells. Hyaluronate synthase from exponential-growth phase cells exhibited lower Km and higher Vmax. values for both UDP-N acetylglucosamine and UDP-glucuronic acid and higher rate of elongation of hyaluronate chains compared with the enzyme from stationary-growth-phase cells. Hyaluronate synthase exhibited an extremely short half-life, 2.2 h and 3.8 h respectively when cells were treated with cycloheximide and actinomycin D. The cell-growth-phase-dependent variations in hyaluronate synthase activity appear to be due to its high turnover rate as well as due to some post-translational modification of the enzyme protein as cells progress from early exponential to stationary growth phase. The isolated plasma membranes contained a protein (Mr approx. 450,000) that was selectively autophosphorylated from [gamma-32P]ATP in vitro in the presence of hyaluronate precursors in the reaction mixture and that also exhibited some hyaluronate-synthesis-related properties. The 32P-labelled protein isolated from plasma membranes of exponentially growing cells expressed an efficient UDP-[14C]glucuronic acid- and UDP-N-acetyl[3H]glucosamine-binding activity and was able to synthesize oligosaccharides (Mr 5000) of [14C]glucuronic acid and N-acetyl[3H]glucosamine residues. The corresponding protein of stationary-growth-phase cells, which expressed much higher nucleotide-sugar precursor-binding activity, appeared to have lost its oligosaccharide synthesizing activity. PMID- 3099757 TI - Structure-function relationships in the free insulin monomer. AB - The chemical properties of the functional groups of insulin were determined at a concentration (0.5 microM) where the predominant species of insulin is the free (unassociated) monomeric unit. The glycine N-terminus and the four tyrosine phenolic groups had the same properties as in the associated forms of insulin. On the other hand the lysine epsilon-amino group and the two histidine imidazole groups had substantially altered properties. Some alteration in the properties of the phenylalanine N-terminus was also observed. The reactivity-pH profile for the imidazole groups showed a second ionization with a pKa of 10.1 in addition to an ionization with a pKa of 6.8. On the basis of the X-ray-crystallographic structure of hexameric insulin the observed changes can be accounted for by disruption of monomer-monomer or dimer-dimer interactions in the associated states of insulin. It is concluded that the conformation of the monomeric unit of insulin is essentially the same in its free and associated states in solution. PMID- 3099756 TI - Hydrolysis of a naturally occurring beta-glucoside by a broad-specificity beta glucosidase from liver. AB - We have isolated from guinea-pig liver a broad-specificity beta-glucosidase of unknown function that utilizes as its substrate non-physiological aryl glycosides (e.g. 4-methylumbelliferyl beta-D-glucopyranoside, p-nitrophenyl beta-D glucopyranoside). The present paper documents that this enzyme can be inhibited by various naturally occurring glycosides, including L-picein, dhurrin and glucocheirolin. In addition, L-picein, which acts as a competitive inhibitor of the broad-specificity beta-glucosidase (Ki 0.65 mM), is also a substrate for this enzyme (Km 0.63 mM; Vmax. 277,000 units/mg). Heat-denaturation, kinetic competition studies, chromatographic properties and pH optima all argue strongly that the broad-specificity beta-glucosidase is responsible for the hydrolysis of both the non-physiological aryl glycosides and L-picein. This paper demonstrates that beta-glucosidase can catalyse the hydrolysis of a natural glycoside, and may provide a key to understanding the function of this enigmatic enzyme. A possible role in the metabolism of xenobiotic compounds is discussed. PMID- 3099758 TI - The activation of protein degradation in muscle by Ca2+ or muscle injury does not involve a lysosomal mechanism. AB - By use of different inhibitors, we distinguished three proteolytic processes in rat skeletal muscle. When soleus muscles maintained under tension were exposed to the calcium ionophore A23187 or were incubated under no tension in the presence of Ca2+, net protein breakdown increased by 50-80%. Although leupeptin and E-64 inhibit this acceleration of protein breakdown almost completely, other agents that prevent lysosomal function, such as methylamine or leucine methyl ester, did not inhibit this effect. A similar increase in net proteolysis occurred in muscle fibres injured by cutting, and this response was also inhibited by leupeptin, but not by methylamine. In contrast, all these inhibitors markedly decreased the 2 fold increase in protein breakdown induced by incubating muscles without insulin and leucine, isoleucine and valine. In addition, the low rate of proteolysis seen in muscles under passive tension in complete medium was not affected by any of these inhibitors. Thus the basal degradative process in muscle does not involve lysosomes or thiol proteinases, and muscle can enhance protein breakdown by two mechanisms: lack of insulin and nutrients enhances a lysosomal process in muscle, as in other cells, whereas Ca2+ and muscle injury activate a distinct pathway involving cytosolic thiol proteinase(s). PMID- 3099755 TI - Increase of adenylate cyclase catalytic-unit activity by dexamethasone in rat osteoblast-like cells. AB - Glucocorticoids are known to increase the cyclic AMP response to parathyroid hormone (PTH) in cultured bone organs or bone cells. Using the osteoblast-like cell line ROS 17/2.8, which possesses receptors for both PTH and glucocorticoids, we investigated which component of the complex hormone receptor-guanine nucleotide regulatory unit--adenylate cyclase was affected by dexamethasone treatment. In response to PTH, isoproterenol or forskolin, a compound that is supposed to act directly on the catalytic unit, cyclic AMP production by intact cells and adenylate cyclase activity in purified plasma membrane were markedly increased by dexamethasone. Whereas NaF, guanosine 5'-[beta gamma imido]triphosphate and Mn/ stimulated adenylate cyclase activity were similarly enhanced in membranes isolated from glucocorticoid-treated cells, the activity of the stimulatory guanine nucleotide regulatory unit, as assessed by reconstitution into membranes from the CYC- clone, which is genetically devoid of this component, was not altered. Thus in osteoblast-like cells dexamethasone appears to increase cyclic AMP synthesis by influencing the catalytic unit. Moreover, since it has been reported that glucocorticoids may produce changes in cell calcium metabolism, we evaluated cytoplasmic free Ca2+ concentration ([Ca2+]i) and intracellular Ca2+ stores mobilizable by the bivalent-cationophore ionomycin, by using the intracellular fluorescent indicator Quin-2. The results indicated that dexamethasone treatment did not influence [Ca2+]i but markedly decreased ionomycin-releasable Ca2+ stores. PMID- 3099759 TI - The use of inhibitors to identify early events during Bacillus megaterium KM spore germination. AB - The germination response of spores of Bacillus megaterium KM, as measured by loss of A600, is more than 95% inhibited by 1 mM-HgCl2. Two Hg2+-sensitive sites (referred to as 'sites I and II') have been identified during germination. Site I represents a pre-commitment event and can be protected from HgCl2 by 50 mM-D alanine, whereas site II represents a post-commitment event and is not D-alanine protectable. At 1 mM-HgCl2, 25% of the spore population becomes committed to germinate, but an A600 loss of less than 5% occurs. In this system, loss of heat resistance was associated with commitment, whereas selective cortex hydrolysis, release of pyridine-2,6-dicarboxylic acid, Zn2+ and soluble peptidoglycan, as well as loss of refractility, were identified as post-commitment events. The commitment event was reversibly inhibited by several proteinase inhibitors and a membrane bulking agent. A model of spore germination based on these results is presented. PMID- 3099760 TI - A simple two-step purification of protease nexin. AB - This paper describes a simple purification procedure for protease nexin, a serine proteinase inhibitor secreted by cultured human fibroblasts that regulates proteinase activity at and near the cell surface. The first step in the procedure takes advantage of the high-affinity binding of protease nexin to dextran sulphate-Sepharose. This step eliminates the need for prior concentration of the serum-free fibroblast-conditioned medium, since protease nexin binds to the resin in the presence of physiological saline. The use of dextran sulphate also provides an affinity resin with considerably less variability than the heparin based resins previously used. Final purification to homogeneity involves a combination of DEAE-Sepharose in-line with dextran sulphate-Sepharose to simultaneously purify and concentrate the protein. Purified protease nexin is shown by Ouchterlony analysis and peptide mapping to be immunologically and structurally distinct from antithrombin III and heparin cofactor II, two plasma proteinase inhibitors with similar properties. PMID- 3099764 TI - Study of the hydrolysis and ionization constants of Schiff base from pyridoxal 5' phosphate and n-hexylamine in partially aqueous solvents. An application to phosphorylase b. AB - Formation and hydrolysis rate constants as well as equilibrium constants of the Schiff base derived from pyridoxal 5'-phosphate and n-hexylamine were determined between pH 3.5 and 7.5 in ethanol/water mixtures (3:17, v/v, and 49:1, v/v). The results indicate that solvent polarity scarcely alters the values of these constants but that they are dependent on the pH. Spectrophotometric titration of this Schiff base was also carried out. We found that a pKa value of 6.1, attributed in high-polarity media to protonation of the pyridine nitrogen atom, is independent of solvent polarity, whereas the pKa of the monoprotonated form of the imine falls from 12.5 in ethanol/water (3:17) to 11.3 in ethanol/water (49:1). Fitting of the experimental results for the hydrolysis to a theoretical model indicates the existence of a group with a pKa value of 6.1 that is crucial in the variation of kinetic constant of hydrolysis with pH. Studies of the reactivity of the coenzyme (pyridoxal 5'-phosphate) of glycogen phosphorylase b with hydroxylamine show that this reaction only occurs when the pH value of solution is below 6.5 and the hydrolysis of imine bond has started. We propose that the decrease in activity of phosphorylase b when the pH value is less than 6.2 must be caused by the cleavage of enzyme-coenzyme binding and that this may be related with protonation of the pyridine nitrogen atom of pyridoxal 5' phosphate. PMID- 3099761 TI - Evidence for the existence of an Ns-type regulatory protein in Trypanosoma cruzi membranes. AB - The existence of a GTP-binding protein of the Ns type in Trypanosoma cruzi was explored. Epimastigote membranes were labelled by cholera toxin in the presence of [adenine-14C]NAD+. After SDS/polyacrylamide-gel electrophoresis of extracted membrane proteins, a single labelled polypeptide band of apparent Mr approx. 45,000 was detected. Epimastigote cells were treated with N-ethylmaleimide and electrofused to lymphoma S49 cells lacking the Ns protein. Evidence indicates that in such electrofusion-generated cell hybrids a heterologous adenylate cyclase system was reconstituted with the Ns protein provided by T. cruzi epimastigotes. PMID- 3099762 TI - Accumulation of N1-acetylspermidine in heart and spleen of isoprenaline-treated rats. AB - N1-Acetylspermidine is not detectable in rat heart, but its content greatly increases after a single injection of isoprenaline (10 mg/kg), reaching a concentration of about 10 nmol/g of tissue 4 h after the treatment. Part of the accumulated N1-acetylspermidine was split to putrescine. Isoprenaline also caused an increase of N1-acetylspermidine in the spleen, where its concentration increased 3.5-fold 6 h after the catecholamine. The accumulation of N1 acetylspermidine was dependent on the dose of isoprenaline in both the heart and the spleen, and was strongly inhibited by beta-antagonists and inhibitors of protein synthesis. PMID- 3099763 TI - Thrombin, unlike vasopressin, appears to stimulate two distinct guanine nucleotide regulatory proteins in human platelets. AB - The thrombin-stimulated GTPase activity of human platelets was additive with respect to the GTPase stimulation effected by prostaglandin E1, but not with that stimulated by adrenaline, vasopressin and platelet-activating factor (PAF). Treatment of platelet membranes with pertussis toxin partially inhibited the thrombin-stimulated GTPase, but had no effect on the vasopressin-stimulated GTPase activity, whereas cholera toxin treatment had no effect on either of these stimulated GTPase activities. Thrombin, adrenaline and PAF, but not vasopressin, inhibited the adenylate cyclase activity of isolated plasma membranes through the action of Ni only, this being inhibited by pertussis toxin. It is suggested that thrombin exerts effects through both the inhibitory guanine nucleotide regulatory protein Ni and through the putative guanine nucleotide regulatory protein, Np, involved in regulating receptor-stimulated inositol phospholipid metabolism. However, vasopressin appears to exert its effects solely through the putative Np. PMID- 3099766 TI - Polyamines and HeLa-cell DNA replication. AB - HeLa cells were synchronized for S-phase DNA synthesis by the double thymidine block procedure. A comparison was made of the polyamine content and S-phase DNA synthesis in cells from control cultures and cultures to which an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine, was added to the synchronization medium. Control cells showed a peak of synchronous DNA synthesis at 3 h and a maximum concentration of polyamines at 6-9 h after release of the second thymidine block. Cells from cultures containing the inhibitor were severely inhibited in the synthesis of DNA and contained no putrescine and only traces of spermidine while the spermine content was lowered by as much as 80%. Supplementation of cultures containing alpha-difluoromethylornithine with a polyamine, at the time of release of the second thymidine block, replenished the intracellular pool of the administered polyamine and partially restored S-phase DNA synthesis, with a lag of 3-6 h. Almost complete restoration of DNA synthesis in cells depleted of polyamines was achieved by the addition of a polyamine to cultures at least 10 h before release of the second thymidine block. The lag in initiation of synchronous S-phase DNA synthesis was eliminated in these cells. It is concluded that reversal by polyamines of the deficiency in S-phase DNA synthesis, in polyamine-depleted HeLa cells, is a time-dependent process indicative of the necessity for the replenishment of replication factors or their organization into an active replication complex. PMID- 3099765 TI - Regulation of arachidonic acid metabolism by cytochrome P-450 in rabbit kidney. AB - Renal microsomal cytochrome P-450-dependent arachidonic acid metabolism was correlated with the level of cytochrome P-450 in the rabbit kidney. Cobalt, an inducer of haem oxygenase, reduced cytochrome P-450 in both the cortex and medulla in association with a 2-fold decrease in aryl-hydrocarbon hydroxylase, an index of cytochrome P-450 activity, and a similar decrease in the formation of cytochrome P-450-dependent arachidonic acid metabolites by renal microsomes (microsomal fractions). Formation of the latter was absolutely dependent on NADPH addition and was prevented by SKF-525A, an inhibitor of cytochrome P-450 dependent enzymes. Arachidonate metabolites of cortical microsomes were identified by g.c.-m.s. as 20- and 19-hydroxyeicosatetraenoic acid, 11,12 epoxyeicosatrienoic acid and 11,12-dihydroxyeicosatrienoic acid. The profile of arachidonic acid metabolites was the same for the medullary microsomes. Induction of cytochrome P-450 by 3-methylcholanthrene and beta-naphthoflavone increased cytochrome P-450 content and aryl-hydrocarbon hydroxylase activity by 2-fold in the cortex and medulla, and this correlated with a 2-fold increase in arachidonic acid metabolites via the cytochrome P-450 pathway. These changes can also be demonstrated in cells isolated from the medullary segment of the thick ascending limb of the loop of Henle, which previously have been shown to metabolize arachidonic acid specifically via the cytochrome P-450-dependent pathway. The specific activity for the formation of arachidonic acid metabolites by this pathway is higher in the kidney than in the liver, the highest activity being in the outer medulla, namely 7.9 microgram as against 2.5 micrograms of arachidonic acid transformed/30 min per nmol of cytochrome P-450 for microsomes obtained from outer medulla and liver respectively. These findings are consistent with high levels of cytochrome P-450 isoenzyme(s), specific for arachidonic acid metabolism, primarily localized in the outer medulla. PMID- 3099767 TI - Substrate specificity and characterization of rat liver p-nitrophenol, 3 alpha hydroxysteroid and 17 beta-hydroxysteroid UDP-glucuronosyltransferases. AB - Purified preparations of rat liver 17-hydroxysteroid, 3-hydroxyandrogen and p nitrophenol (3-methylcholanthrene-inducible) UDP-glucuronosyltransferases were further characterized as to their substrate specificities, phospholipid dependency and physical properties. The two steroid UDP-glucuronosyltransferases were shown to exhibit strict stereospecificity with respect to the conjugation of steroids and bile acids. These enzymes have been renamed 17 beta-hydroxysteroid and 3 alpha-hydroxysteroid UDP-glucuronosyltransferase to reflect this specificity for important endogenous substrates. An endogenous substrate has not yet been identified for the p-nitrophenol (3-methylcholanthrene-inducible) UDP glucuronosyltransferase. The steroid UDP-glucuronosyltransferase activities were dependent on phospholipid for maximal catalytic activity. Complete delipidation rendered the UDP-glucuronosyltransferases inactive, and enzymic activity was not restored when phospholipid was added to the reaction mixture. After partial delipidation, phosphatidylcholine was the most efficient phospholipid for restoration of enzymic activity. Partial delipidation also altered the kinetic parameters of the 3 alpha-hydroxysteroid UDP-glucuronosyltransferase. The three purified UDP-glucuronosyltransferases are separate and distinct proteins, with different amino acid compositions and peptide maps generated by limited proteolysis with Staphylococcus aureus V8 proteinase. Some similarity was observed between the amino acid composition and limited proteolytic maps of the steroid UDP-glucuronosyltransferases, suggesting they are more closely related to each other than to the p-nitrophenol UDP-glucuronosyltransferase. PMID- 3099769 TI - The human growth hormone receptor of cultured human lymphocytes. Structural characteristics and glycosylation properties. AB - The structural characteristics and glycoprotein nature of the human growth hormone (hGH) receptor in cultured lymphocytes (IM-9 cell line) were studied with the use of a bifunctional reagent (disuccinimidyl suberate) to couple 125I-hGH covalently to intact cells. After cross-linking, the hormone-receptor complexes were analysed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. A single band of Mr 140,000 was identified under reducing conditions. The labelling of this band was blocked by unlabelled hGH but not by insulin, ovine prolactin, bovine or ovine growth hormones. The Mr 140,000 band was immunoprecipitated by either anti-hGH antibody or by a monoclonal antibody against rat liver growth hormone receptor. In the absence of reductant two major bands of Mr 270,000 and 140,000 were found. On two-dimensional gel electrophoresis, with the first dimension in the absence of reductant and the second in its presence, the Mr 270,000 complex generated the Mr 140,000 band. The nature of the oligosaccharide chains of the receptor was studied by treatment with different glycosidases. The electrophoretic mobility of the Mr 140,000 receptor complex was markedly increased after digestion with endoglycosidase F but showed no or little change after digestion with endoglycosidase H. The Mr 140,000 band was also sensitive to neuraminidase treatment. In addition the 125I-hGH-receptor complex was adsorbed by immobilized wheat germ agglutinin and to a smaller extent by immobilized concanavalin A, lentil lectin, ricin I and ricin II. In conclusion, taking into account that hGH is a Mr 22,000 polypeptide, the binding subunit of the GH receptor in human IM-9 lymphocytes has an Mr of approx. 120,000. The native receptor may exist as a homodimer of the binding subunit formed by disulphide bonds. Furthermore, the GH receptor subunit contains asparagine N-linked type of oligosaccharide chains. Most, if not all, of these chains are of the complex type and appear to be sialylated whereas no high-mannose type chains are detectable in the mature form of the receptor. PMID- 3099770 TI - Characterization of lysosomes and lysosomal enzymes from Chediak-Higashi-syndrome cultured fibroblasts. AB - Chediak-Higashi-syndrome cultured skin fibroblasts were used to study the possible involvement of lysosomal enzymes and lysosomal dysfunction in this disorder. Our evidence indicated that Chediak-Higashi fibroblasts displayed a significant decrease in the specific activity of the acidic alpha-D-mannosidase (pH 4.2) compared with normal controls. Additional studies revealed a small, but significant, decrease in the rate of degradation of 125I-labelled beta-D glucosidase that had been endocytosed into Chediak-Higashi cells. PMID- 3099768 TI - Effect of hepatocyte-stimulating factor and glucocorticoids on plasma fibronectin levels. AB - We evaluated the effects of hepatocyte-stimulating factor (HSF) and a glucocorticoid (dexamethasone) on changes in the levels, in vivo and in vitro, of plasma fibronectin (Fn), a glycoprotein that is synthesized and secreted by hepatocytes. In turpentine-treated chickens, plasma levels of Fn, which peaked at 48 h (whereas fibrinogen levels were maximum at 72 h) rose 200-250% over basal levels, whereas albumin levels decreased by 20-40%. Corticosterone levels in serum samples taken between 5 and 48 h after injection revealed a 124% increase in hormone levels at 24 h in turpentine-treated chickens. We also showed that circulating HSF levels were maximal 8 to 12 h after injection and that HSF activity, as assessed by molecular-exclusion chromatography, was eluted in the 30 45 kDa range. Addition of either serum-derived HSF or dexamethasone (2 nM) to chick hepatocyte cultures resulted in a 130-150% increase in secreted Fn as well as in fibrinogen. When HSF and dexamethasone were added together, a 360-489% increase in the secreted levels of both proteins was found. Chicken mononuclear phagocytic cells treated with lipopolysaccharide secreted an HSF activity that was eluted in two peaks, a minor peak at approximately 70 kDa and a major peak in the 25-40 kDa range. Addition of mononuclear-cell-derived HSF resulted in a greater increase in Fn levels than did the addition of serum HSF. These findings indicate that Fn, like fibrinogen, is an acute-phase protein, the production of which, at least in chickens, is stimulated by HSF and glucocorticoids in an additive manner. PMID- 3099771 TI - Clearance of the heavy and light polypeptide chains of human tissue-type plasminogen activator in rats. AB - In order to assess which part of the tissue-type plasminogen activator (t-PA) molecule should be (genetically) modified to obtain more-slowly-clearing mutants, two-chain t-PA and its isolated heavy and light chains were radiolabelled and injected into rats. The vast majority of t-PA and the heavy chain disappeared from the blood circulation with half-lives of 2.3 and 1.0 min respectively. The clearance of the light chain was biphasic, owing to complex-formation with plasma proteinase inhibitors. The disappearance of di-isopropylphospho-light chain, which has a blocked active site, was nearly monophasic, with a half-life of 5.7 min. Organ distribution studies showed that hepatic clearance constituted the major pathway in all cases. These results strongly suggest that t-PA is recognized by the liver primarily through the heavy chain. PMID- 3099772 TI - Rapid purification of tissue inhibitor of metalloproteinases from human plasma and identification as a gamma-serum protein. AB - A rapid method is described for the purification of human tissue inhibitor of metalloproteinases (TIMP) from plasma which involves immuno-affinity chromatography and gel filtration. The purified plasma inhibitor is immunologically identical with the TIMP previously purified from human amniotic fluid, human synovial fluid and human fibroblast culture medium. It is proposed that this inhibitor is identical with the plasma inhibitor previously named 'B1 anticollagenase', although the plasma inhibitor was shown to migrate as a gamma serum component. PMID- 3099773 TI - Ionophore A23187 induces a refractory state in thrombin-activated release of inositol phosphates. AB - The phosphatidylinositol cycle has been proposed to be involved in the regulation of platelet functionality through the control of cytoplasmic Ca2+ levels. However, the requirements of phospholipase C for Ca2+ has not yet been elucidated in intact platelets. The primary purpose of the present study was to investigate the Ca2+ requirements of this enzyme in platelets from miniature swine by taking advantage of the permeabilizing properties of the ionophore A23187. Our results strongly suggest that the treatment of platelets with A23187 induces a refractory state in thrombin-stimulated release of inositol phosphates while 5 hydroxytryptamine (serotonin)-secretory capacity in response to thrombin remained constant. This refractory state seems to be dependent on some cytochalasin inhibitable cytoskeletal phenomena. PMID- 3099776 TI - Age-related augmentation of phosphorylase b kinase in hepatic tissue from the glycogen-storage-disease (gsd/gsd) rat. AB - The effects of food deprivation on body weight, liver weight, hepatic glycogen content, glycogenolytic enzymes and blood metabolites were compared in young and old phosphorylase b kinase-deficient (gsd/gsd) rats. Although the concentration of glycogen in liver from 9-week-old female gsd/gsd rats (730 mumol of glucose equivalents/g wet wt.) was increased by 7-8% during starvation, total hepatic glycogen was decreased by 12% after 24 h without food. In 12-month-old male gsd/gsd rats the concentration of liver glycogen (585 mumol of glucose equiv./g wet wt.) was decreased by 16% and total hepatic glycogen by nearly 40% after food deprivation for 24 h. Phosphorylase b kinase and phosphorylase a were present at approx. 10% of the control activities in 9-week-old gsd/gsd rats, but both enzyme activities were increased more than 3-fold in 12-month-old affected rodents. It is concluded that the age-related ability to mobilize hepatic glycogen appears to result from the augmentation of phosphorylase b kinase during maturation of the gsd/gsd rat. PMID- 3099775 TI - Effects of vasopressin and La3+ on plasma-membrane Ca2+ inflow and Ca2+ disposition in isolated hepatocytes. Evidence that vasopressin inhibits Ca2+ disposition. AB - Vasopressin caused a 40% inhibition of 45Ca uptake after the addition of 0.1 mM 45Ca2+ to Ca2+-deprived hepatocytes. At 1.3 mM-45Ca2+, vasopressin and ionophore A23187 each caused a 10% inhibition of 45Ca2+ uptake, whereas La3+ increased the rate of 45Ca2+ uptake by Ca2+-deprived cells. Under steady-state conditions at 1.3 mM extracellular Ca2+ (Ca2+o), vasopressin and La3+ each increased the rate of 45Ca2+ exchange. The concentrations of vasopressin that gave half-maximal stimulation of 45Ca2+ exchange and glycogen phosphorylase activity were similar. At 0.1 mM-Ca2+o, La3+ increased, but vasopressin did not alter, the rate of 45Ca2+ exchange. The results of experiments performed with EGTA or A23187 or by subcellular fractionation indicate that the Ca2+ taken up by hepatocytes in the presence of La3+ is located within the cell. The addition of 1.3 mM-Ca2+o to Ca2+ deprived cells caused increases of approx. 50% in the concentration of free Ca2+ in the cytoplasm [( Ca2+]i) and in glycogen phosphorylase activity. Much larger increases in these parameters were observed in the presence of vasopressin or ionophore A23187. In contrast with vasopressin, La3+ did not cause a detectable increase in glycogen phosphorylase activity or in [Ca2+]i. It is concluded that an increase in plasma membrane Ca2+ inflow does not by itself increase [Ca2+]i, and hence that the ability of vasopressin to maintain increased [Ca2+]i over a period of time is dependent on inhibition of the intracellular removal of Ca2+. PMID- 3099774 TI - Ca2+ and Zn2+-binding properties of nitrated S-100b protein from bovine brain. AB - The single tyrosine residue in S-100b protein was nitrated by treatment with tetranitromethane in 0.1 M-Tris/HCl buffer, pH 8.0, containing 2 mM-EDTA. The nitrated protein did not differ significantly in secondary structure from its native unmodified counterpart, as revealed by far-u.v. c.d. measurements. The effect of Ca2+ on the modified protein was different from that on the native protein, e.g. addition of Ca2+ resulted in a loss of helical content from 55 to 47% with the native protein whereas Ca2+ had no significant effect on the gross conformation of the nitrated derivative. Near-u.v. c.d. studies also indicated a very minimal effect on the tyrosine residue and this was also reflected in the u.v.-absorption difference spectrum. Polyacrylamide-gel electrophoresis in the absence of SDS showed the nitrated S-100b to move faster in the presence of EDTA compared with the calcium-bound state, suggesting that the modified protein does bind Ca2+ although it does not undergo a major conformational change in response to Ca2+ addition. In contradistinction, Zn2+ binding was not influenced by nitration, as demonstrated by aromatic c.d. and u.v.-difference spectroscopy. It is clear from this study that the single tyrosine residue in S-100b is critical to sense the Ca2+-induced conformational changes in the protein. PMID- 3099777 TI - Temporal patterns of protein phosphorylation after angiotensin II, A23187 and/or 12-O-tetradecanoylphorbol 13-acetate in adrenal glomerulosa cells. AB - The temporal patterns of protein phosphorylation in the adrenal glomerulosa cell were analysed by two-dimensional electrophoresis after stimulation with 10 nM angiotensin II or various agents [10 nM-12-O-tetradecanoylphorbol 13-acetate (TPA), 50 nM-A23187, 1 microM-nitrendipine], administered singly or in combination. These patterns were compared with the temporal patterns of aldosterone secretion induced by the same agonists and antagonists. After 1 and 30 min of stimulation with angiotensin II, different patterns of protein phosphorylation were observed. A comparison of these patterns reveals that: the phosphorylation of only one protein was persistently enhanced during the continuous incubation with angiotensin II; the phosphorylation of five proteins was transiently enhanced (at 1 min but not 30 min); and the phosphorylation of three proteins did not occur at 1 min but was seen at 30 min. Addition of the phorbol ester TPA alone, which at 30 min is without effect in enhancing aldosterone production, has no effect on protein phosphorylation. The combined addition of TPA and the Ca2+ ionophore, A23187, which, like angiotensin II, evokes a sustained increase in aldosterone production, reproduced the temporal patterns of protein phosphorylation seen after angiotensin II action. Manipulations (A23187 alone, angiotensin II plus nitrendipine) which evoke only a transient rise in aldosterone production rate induce a transient rise in cellular protein phosphorylation. The 1 min patterns of phosphorylation seen after A23187 or combined angiotensin II and nitrendipine (a Ca2+ channel antagonist) are similar to those observed after 1 min of angiotensin II stimulation. These results suggest that, when angiotensin II acts, the initial cellular response is mediated by a different mechanism than that responsible for the sustained response. PMID- 3099779 TI - Evidence for conservation of dietary lipid in the rat during lactation and the immediate period after removal of the litter. Decreased oxidation of oral [1 14C]triolein. AB - Production of 14CO2 from an oral load of [1-14C]triolein was greatly decreased (70%) in lactating rats or immediately after (24-48 h) removal of the litter, compared with virgin rats. This decreased oxidation of dietary lipid was accompanied by accumulation of 14C-labelled lipid in lactating mammary gland or adipose tissue (after litter removal). No difference in 14CO2 production between lactating and virgin rats was observed when [1-14C]octanoate was administered. It is concluded that a major factor in this conservation of dietary triacylglycerol is the relative activity of lipoprotein lipase in the tissues. PMID- 3099781 TI - Glycosylation inhibitors block the expression of LAV/HTLV-III (HIV) glycoproteins. AB - The glycosylation inhibitors 2-deoxy-D-glucose (2-dGlc) and, to a lesser extent, beta-hydroxynorvaline blocked the formation of syncytia in HIV (LAV/HTLV-III) infected cells. Using monospecific polyclonal antibodies against recombinant envelope proteins gp110 and gp41 or monoclonal antibodies against env gp110, we could demonstrate a marked reduction in the immunoreactivity of these antigens in HIV-infected cells exposed to the glycosylation inhibitors. There was concomitant accumulation of core proteins p15 and p24, as shown by a solid phase radio immunoassay, and a decreased oligosaccharide synthesis of env proteins, as monitored by the incorporation of [6-3H]GlcNAc. The reverse transcriptase was not affected by the compounds. Glycosylation inhibitors may be considered for the chemotherapy of AIDS or AIDS-related complex, or chemoprophylaxis of HIV-positive individuals. PMID- 3099778 TI - The reversible Ca2+-induced permeabilization of rat liver mitochondria. AB - Rat liver mitochondria became permeabilized to sucrose according to an apparent first-order process after accumulating 35 nmol of Ca2+/mg of protein in the presence of 2.5 mM-Pi, but not in its absence. A fraction (24-32%) of the internal space remains sucrose-inaccessible. The rate constant for permeabilization to sucrose decreases slightly when the pH is decreased from 7.5 to 6.5, whereas the rate of inner-membrane potential (delta psi) dissipation is markedly increased, which indicates that H+ permeation precedes sucrose permeation. Permeabilization does not release mitochondrial proteins. [14C]Sucrose appears to enter permeabilized mitochondria instantaneously. Chelation of Ca2+ with EGTA restores delta psi and entraps sucrose in the matrix space. With 20 mM-sucrose at the instant of resealing, about 21 nmol of sucrose/mg of protein becomes entrapped. The amount of sucrose entrapped is proportional to the degree of permeabilization. Entrapped sucrose is not removed by dilution of the mitochondrial suspension. Resealed mitochondria washed three times retain about 74% of the entrapped sucrose. In the presence of Ruthenium Red and Ca2+ buffers permeabilized mitochondria reseal only partially with free [Ca2+] greater than 3 microM. [14C]Sucrose enters partially resealed mitochondria continuously with time, despite maintenance of delta psi, in accordance with continued interconversion of permeable and impermeable forms. Kinetic analyses of [14C]sucrose entry indicate two Ca2+-sensitive reactions in permeabilization. This conclusion is supported by the biphasic time courses of resealing and repolarization of permeabilized mitochondria and the acute dependence of the rapid repolarization on the free [Ca2+]. A hypothetical model of permeabilization and resealing is suggested and the potential of the procedure for matrix entrapment of substances is discussed. PMID- 3099780 TI - Purification of human procollagen type III N-proteinase from placenta and preparation of antiserum. AB - Procollagen type III N-proteinase, of Mr about 70,000, was detected in human placental tissue and purified from this source more than 5800-fold. It was found to be a glycoprotein, which was bound to both concanavalin A-Ultrogel and heparin Sepharose affinity columns. Binding to a type III pN-collagen-Sepharose affinity column was used as the final step in purification. The purified enzyme accepted only native type III procollagen or [14C]carboxymethylated type III pN-collagen as its substrate; type I, type II and type IV procollagen and heat-denatured type III pN-collagen were not cleaved by the enzyme. Antibodies against this purified enzyme protein raised in rabbits demonstrated a high inhibitory effect on the enzyme activity. Immunoblotting of the denatured protein and immunoelectrophoresis of the native enzyme showed only one major antigenic component, again with an Mr of about 70,000. The antibodies cross-reacted with the enzyme preparation from foetal-calf aorta smooth-muscle cells. PMID- 3099782 TI - Phospholipase C-diglyceride lipase is a major pathway for arachidonic acid release in macrophages. AB - Macrophages are a rich source of arachidonic acid oxygenated metabolites and play a remarkable role in a number of physiopathological situations. The synthesis and secretion of arachidonic acid metabolites are triggered at the cytoplasmic membrane level. The present study was outlined to further investigate the cellular mechanisms controlling arachidonic acid release in macrophages. The results presented here strongly suggest that the amount of arachidonic acid released in macrophages in response to phagocytic challenge could be accounted for by a phospholipase C-diglyceride lipase system being unnecessary the presence of phospholipase A2 whose activity, on the other hand, was found vanishingly small in macrophage homogenates. PMID- 3099785 TI - Induction of cytochrome P-450 in Streptomyces griseus by soybean flour. AB - Soybean flour and the isoflavonoid genistein, were found to induce cytochrome P 450 in Streptomyces griseus. The chromophore was found in the 105,000xg supernatant and gave a reduced CO-difference spectrum with an absorption maximum of 448 nm. Almost 70% of the P-450 could be precipitated at 35-45% ammonium sulfate saturation. SDS-gel electrophoresis revealed the presence of a 45,000 dalton polypeptide in extracts induced by either soybean or genistein. S. griseus generated the free isoflavonoids genistein and daidzein when grown on soybean flour medium. PMID- 3099783 TI - Different concentrations of pertussis toxin have opposite effects on agonist induced PGE2 formation in mesangial cells. AB - Pertussis toxin may inactivate N proteins linked to phospholipase C. We examined the effect of pretreatment with pertussis toxin at different concentrations and times on agonist-induced PGE2 synthesis in mesangial cells. Two to four hours with 10-50 ng/ml of pertussis toxin inhibited the response to angiotensin and platelet activating factor, but with a different sensitivity. This was associated with decreased [14C]arachidonic acid release in prelabeled cells. The response to A23187 was unaltered. At high concentrations (1 to 5 micrograms/ml) pertussis toxin increased basal PGE2 and the response to all agonists. Pertussis toxin pretreatment resulted in a dose-dependent ribosylation of a 40 kDa protein band. Thus, responses to different agonists have different sensitivity to pertussis toxin inhibition, which at high concentrations may even have opposite effects. PMID- 3099784 TI - Identification of UDP-galactose: lactose (lactosylceramide) alpha-4 and beta-3 galactosyltransferases in human kidney. AB - Two galactosyltransferases were identified in human kidney microsomes which both transfer galactose from UDP Gal to lactose as well as to lactosylceramide. Using a solubilized and a partially purified enzyme preparation sufficient product could be obtained for detailed structural analysis. The trisaccharide products were isolated by gel permeation chromatography and separated by preparative high performance thin layer chromatography. The anomeric configuration of the transferred galactose was determined by specific glycosidase digestion and the linkage was identified by methylation and gas-liquid-chromatography. The glycolipid products were not separated but analyzed directly, before and after alpha or beta galactosidase digestion, by methylation, hydrolysis and thin layer chromatography. Into both acceptor substrates galactose was incorporated in alpha 1-4 (30%) and beta 1-3 (70%) linkages. The alpha 1-4 galactosyltransferase is responsible for the synthesis of the Pk antigen Gal alpha 1-4 Gal beta 1-4 Glc ceramide in human kidney. The beta 1-3 galactosyltransferase has not previously been identified. PMID- 3099786 TI - HSP 26 and 27 are phosphorylated in response to heat shock and ecdysterone in Drosophila melanogaster cells. AB - Protein phosphorylation has been studied in Drosophila melanogaster 8.9 K cells following heat shock. By in vivo double labelling with [35S]-methionine and [32P] orthophosphate, we observed that two proteins are newly phosphorylated among the 26,000-27,000 dalton heat-shock proteins group. These two proteins are also phosphorylated after ecdysterone treatment, albeit at a lower level. That this phosphorylation event is induced by two different treatments, i.e. ecdysterone, a key steroid hormone of development, and heat-shock, a cellular stress suggests a possible common pathway for those two events and an important function for the phosphorylated heat-shock proteins. PMID- 3099787 TI - Cloning of a Drosophila cDNA encoding a polypeptide similar to the human insulin receptor precursor. AB - A Drosophila cDNA clone was obtained using the human insulin receptor cDNA sequence as a probe. The 3586 bp nucleotide sequence predicted a single polypeptide of 1095 amino acid residues which showed considerable homology (35.2%) with the human insulin receptor precursor. Although the cDNA was incomplete at its 5'-terminal region, it encodes a transmembrane glycoprotein as a single precursor of a two subunit molecule having a structural architecture similar to that of the human insulin receptor precursor. The presumptive beta subunit carries a well conserved Tyr kinase domain which showed 63.5% homology with that of human insulin receptor; however the protein of the alpha subunit is only weakly conserved (25%). PMID- 3099790 TI - Modulation of rat polymorphonuclear leukocyte 5-lipoxygenase activity by 5-HPETE and NADH-dependent flavin inhibition. AB - The effect of nicotinamide and flavin coenzymes on the 5-lipoxygenase activity has been determined in cell-free extracts from rat polymorphonuclear leukocytes. 5-lipoxygenase was assayed in the presence of 5-hydroperoxyeicosatetraenoic acid (5-HPETE), which caused a 3 to 4-fold stimulation in the maximal conversion of radiolabeled arachidonic acid to 5-hydroxyeicosatetraenoic acid (5-HETE) and 5,12 dihydroxyeicosatetraenoic acid (5,12-di-HETE). Addition of FMN or FAD to the assay mixture had little effect on the 5-lipoxygenase activity and caused inhibition only at high concentrations (IC50 greater than 100 microM). NADH markedly potentiated the inhibition of lipoxygenase by flavins with a 100-fold decrease in the FMN concentration required to inhibit the enzyme (IC50 approximately equal to 2 microM). Similar effects were observed for FAD although this flavin derivative was slightly less potent than FMN (IC50 congruent to 10 microM). NADH could be substituted by NADPH but not by NAD or NADP, indicating that the inhibition was not due to the production of the oxidized forms of these co-factors. These results show that the 5-lipoxygenase activity is stimulated by 5-HPETE and inhibited by flavin-dependent redox transformations. PMID- 3099788 TI - Phorbol ester causes short term and transient accumulation of pteridines in T cells and in cell lines. AB - Upon exposure to 12-O-tetradecanoylphorbol 13-acetate, interleukin 2 receptor+ T cells transiently accumulate neopterin and biopterin as was determined by HPLC after iodine oxidation of acidic cell extracts. Pteridines peak at maximally 20 fold levels after 10-20 min and return to initial levels during the following 30 40 min. Resting human peripheral blood mononuclear cells do not react within this short period. TPA elicits similar neopterin and biopterin accumulation kinetics in cell lines such as HL-60, Reh, Jurkat JMN, HeLa and 293, whereby HL-60 and Reh release substantial amounts of these transiently formed pteridines into the medium. PMID- 3099789 TI - Characterization of two heme oxygenase isoforms in rat spleen: comparison with the hematin-induced and constitutive isoforms of the liver. AB - Two isoforms of heme oxygenase, designated as HO-1 and HO-2, were identified in rat spleen. The most abundant form was HO-1, wherein a relative ratio of about 5:1 of HO-1 to HO-2 was detected. The splenic HO-1 and HO-2 were immunochemically similar to the purified isoforms obtained from the liver and the testis. Moreover, the elution properties of splenic HO-1 as well as those of the constitutive liver HO-1 and the hematin-induced liver HO-1 on a DEAE-sephacel column were similar. However, the splenic HO-1 activity could not be induced by hematin. It is suggested that in the spleen heme oxygenase activity is maintained in the induced state as the result of constant exposure to hemoglobin released in the course of disruption of senescent erythrocytes. PMID- 3099792 TI - In vitro translation of mushroom tyrosinase. AB - Mushroom tyrosinase was purified and antibodies prepared against the holo enzyme and a protein of 26,000 daltons. Both antibodies recognized the large subunit of the enzyme but only one recognized the 26,000 dalton protein. Poly A+ mRNA was isolated from mushrooms, translated in vitro, and a 41,000 dalton protein immunoprecipitated from the translation mix with either antibody. This 41,000 dalton protein presumably corresponds to the large subunit of the holoenzyme. Antibodies against the holoenzyme also immunoprecipitated another translation product with a molecular weight of 15,000 daltons corresponding to the small subunit of the holoenzyme. These results suggest that each subunit may be coded for by different genes and undergo posttranslational processing. PMID- 3099791 TI - Carbamylcholine, TRH, PGF2 alpha and fluoride enhance free intracellular Ca++ and Ca++ translocation in dog thyroid cells. AB - Effects on Ca++ translocation and [Ca++]i were studied in dog thyroid cell monolayers using both 45Ca++ efflux and the indicator quin-2. Carbamylcholine, a non hydrolysable analog of acetylcholine, through muscarinic receptors, and to a lesser extent TRH and PGF2 alpha increased both these parameters. [Ca++]i increased by 171, 100 and 75% respectively over a basal level of 66 +/- 17 nM (mean +/- SD). The response to carbamylcholine was biphasic. A transient increase in [Ca++]i was followed by a more sustained phase where the [Ca++]i was slightly higher than the basal level. Only the first phase was insensitive to extracellular Ca++ depletion. This phase is probably due to a release of Ca++ from an intracellular store. NaF also induced a sustained rise in [Ca++]i dependent on extracellular Ca++ and affected 45Ca++ efflux. Our data provide direct evidence of an implication of intracellular Ca++ in the response of dog thyroid cells to all these agents. PMID- 3099793 TI - Self assembly of microtubule associated protein tau into filaments resembling those found in Alzheimer disease. AB - Microtubule associated protein tau factor self-assembles into filamentous structures resembling the paired helical filaments found in Alzheimer disease. Tau polymerization requires of a previous modification; conversion of glutamine into glutamic acid by deamination. PMID- 3099794 TI - Inactivation of skeletal glycogen synthetase by diethylpyrocarbonate. AB - Glycogen synthetase from skeletal muscle is rapidly inactivated by DEPC. In the presence of the substrate UDPG only 50% of the enzyme activity is lost. The concomitant addition of both UDPG and the allosteric activator glucose-6 phosphate almost completely prevents the inactivation by DEPC. Since glucose-6 phosphate alone does not prevent the inactivation by DEPC, it is concluded that it is effective through a potentiation of the effects of UDPG, possibly through a conformational change of the enzyme. PMID- 3099795 TI - Genes encoding threonine tRNAs with the anticodon CGU from Escherichia coli and Pseudomonas aeruginosa. AB - Homologous genes for threonine tRNAs with the anticodon CGU have been identified in the region of the proBA operon of Escherichia coli and downstream from the fimbrial subunit gene of Pseudomonas aeruginosa. tRNAs with the anticodon CGU have not previously been identified from either of these bacterial species. Sequence analyses have shown that these genes are similar to other bacterial tRNA genes, and that the predicted structure conforms to the standard cloverleaf model, including retention of all invariant and semi-invariant bases. Analysis of upstream sequences suggests that these genes have associated promoters and are probably expressed in vivo. PMID- 3099796 TI - Characterization and immunochemistry of pyruvate dehydrogenase complex of Ascaris muscle. AB - Pyruvate dehydrogenase complex and lipoamide dehydrogenase were purified from muscle of Ascaris lumbricoides var. suum which contains relatively a large amount of the complex. Molecular weights of three constituent enzymes of Ascaris pyruvate dehydrogenase complex were as follows; alpha- and beta-subunits of pyruvate dehydrogenase were 42,000 and 37,000, respectively, lipoate acetyltransferase was 76,000 and lipoamide dehydrogenase was 56,000. Furthermore, two unknown polypeptides having molecular weight of 46,000 and 41,000 were detected. Anti-Ascaris lipoamide dehydrogenase antibody precipitated three constituent enzymes and two unknown polypeptides, suggesting that lipoamide dehydrogenase not only binds tightly to complex, but also two unknown polypeptides bind tightly to complex. PMID- 3099797 TI - Action of Mn2+ and vanadium compounds on hormone and forskolin induced stimulation of juvenile rat ovarian adenylate cyclase. AB - The effect of forskolin on the hormonal (LH, FSH) activation and on the stimulation provided by other effectors (Gpp(NH)p,NaF) of the juvenile rat ovarian adenylate cyclase was investigated. Forskolin exhibited a synergistic action with LH, FSH and Gpp(NH)p but not with NaF. Addition of Ca2+ was inhibitory over a concentration range from 10(-5) to 10(-2) M whereas EGTA enhanced the response at 5.10(-5) M and inhibited it at higher concentration. The cAMP production was increased by addition of Mn2+ at low concentration (up to 5 mM) but markedly decreased at higher concentration (30 mM). FSH induced cAMP production was completely abolished at 30 mM Mn2+. The effect of vanadyl ion was very similar to that of Mn2+ Vanadate anion on the contrary was without effect on FSH stimulation. PMID- 3099798 TI - Effects of AGEPC on the intracellular levels of ions in Tetrahymena pyriformis. AB - 1-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine(Platelet Activating Factor) is a very potent stimulator of Ca2+ influx into the cells of Tetrahymena pyriformis; increases the levels of bound and free intracellular Ca2+ and this effect is time and dose-dependent. Also AGEPC enhances the Na+ influx into the cells, while has no effect on the intracellular levels of K+ and on the packed cell volume. The effects of AGEPC on intracellular Ca2+ and Na+ are completely inhibited by verapamil which also inhibits the Ca2+ influx observed in the control, but has not any effect on the Na+ uptake observed in the control. These results provide evidence that the effect of AGEPC on Na+ influx, depends on its effect on free intracellular Ca2+. The non acetylated derivative of AGEPC, lyso-GEPC has no effect on all the studied parameters. PMID- 3099799 TI - On the mode of action of phlorizin as an antimalarial agent in in vitro cultures of Plasmodium falciparum. AB - Phlorizin (phloretin-2-beta-glucoside) is a drug which effectively inhibits intraerythrocytic malaria growth in in vitro cultures of Plasmodium falciparum IC50 = 16 +/- 7 microM). Work with synchronously grown cultures indicates that susceptibility to phlorizin is apparent at the trophozoite stage and onward, and that 2-8 hours exposure to the drug causes an irreversible arrest of parasite growth. The drug has also been found to inhibit pores which are induced by the parasite in the host cell membrane (IC50 = 17 +/- 2 microM) and which are apparently essential for intraerythrocytic growth. The effect on the pores is apparent soon after exposure of the cells to the drug and can be reversed, although extensive washing and incubation in culture conditions are required to achieve it. The results of this study indicate that the putative site of action of phlorizin on the pores is on the cytoplasmic surface of the host cell membrane. The drug which normally cannot permeate uninfected red cells, gains access to the cytoplasm via the pores, appearing in the host cell membrane. Those become eventually the target of phlorizin itself. The proposed mechanism of action of phlorizin on malarial growth invokes blockade of the pores, although additional effects of the drug on intraerythrocytic parasites cannot be ruled out. PMID- 3099800 TI - HLA-DR antigens in gold-induced neutropenia. AB - We studied the clinical courses of 9 patients who developed acute gold-induced neutropenia with marrow aplasia. Eight of these carried HLA-DR4, compared with only 2 of 9 who had mild, chronic, isolated neutropenia (P less than 0.05). Only 1 of 9 patients with myelotoxicity carried HLA-DR3. We conclude that these groups are immunogenetically distinct, and that HLA-DR3 is not a significant risk factor for severe gold-induced neutropenia. PMID- 3099801 TI - Sjogren-like syndrome in kappa chain deficiency. PMID- 3099802 TI - Cytotoxic effect of serum on fibroblasts in one case of normolipidemic plane xanthoma and myeloma IgG lambda. AB - Serum was examined for a cytotoxic effect on cultured human fibroblasts, using 8 normal controls and 4 patients. Three of the patients had secondary lipidoses associated with monoclonal gammapathies of IgA kappa, IgG kappa and IgG lambda types. The fourth had systemic lupus erythematosus (SLE) with hyperlipidemia. Only serum containing the monoclonal IgG lambda was found to be cytotoxic. This circulating IgG lambda was strongly bound to HDL and behaved like an antilipoprotein antibody. The circulating immune complexes may be the serum factor responsible for the cytotoxicity and the cutaneous plane xanthomas, thus giving another example of 'antibody-dependent' cellular cytotoxicity previously described for endothelial cells in other diseases. PMID- 3099806 TI - Perinephric and subhepatic abscesses associated with renal subcapsular islet cell transplantation. PMID- 3099803 TI - Metabolism of apolipoprotein C-I in normolipoproteinemic human subjects. AB - Labeling of apolipoprotein C-I by the Bolton and Hunter reagent allowed a study of the kinetics of this peptide in normolipidemic human volunteers. After its intravenous injection the appearance of radioactivity of the labeled apoprotein was followed in plasma, lipoprotein fractions, and urine for 15 days. Apolipoprotein C-I was quickly associated with HDL and to a smaller extent with VLDL in in vitro and in vivo incubation. Kinetic parameters of apolipoprotein C-I were compared with those of apo A-I. Fractional catabolic rates are respectively 0.422 +/- 0.044 vs 0.240 +/- 0.003 pools/day, residence times through the whole system 3.24 +/- 0.27 vs 6.31 +/- 0.27 days and production rates 1.79 +/- 0.18 vs 13.2 +/- 2.1 mg/kg X day. Two explanations for these differences are proposed. PMID- 3099804 TI - Is the ratio of apo B/apo A-I an early predictor of coronary atherosclerosis? AB - It is unknown which lipoprotein in childhood is the best predictor of atherosclerosis later on in life. We measured serum triglycerides, total cholesterol, its subfractions (LDL, HDL, HDL2, HDL3) and apoproteins (A-I, A-II, B) in two groups of children. They were offspring of fathers who had severe coronary atherosclerosis or no coronary sclerosis, as determined by coronary angiography. Fasting blood lipids were measured in 49 children of fathers with severe sclerosis, and in 37 children of fathers without sclerosis. Sons of fathers with severe coronary atherosclerosis had higher levels of apo B and of the ratio apo B/apo A-I than sons of fathers free of atherosclerosis. No differences in lipid levels in daughters were observed. These observations suggest that apolipoproteins play a part in early atherogenesis. They further indicate that it may be possible to detect children who have a high probability of developing severe coronary atherosclerosis later in life. PMID- 3099805 TI - Schistosomiasis in the Dominican Republic. Detection of antibodies by radioimmunoassay. PMID- 3099807 TI - [Development of equipment for artificial respiration of infants and children. 2. The "Baby Ventilator I" long-term respirator for infants and children]. PMID- 3099809 TI - [Effect of dalargin on morphologic and functional indices in experimental myocardial infarct]. PMID- 3099811 TI - Effects of benzydamine and other non-steroidal anti-inflammatory drugs on platelet aggregation induced by: arachidonic acid, ADP and collagen. PMID- 3099808 TI - [Dinitrosorbilong--a new Soviet anti-angina preparation. Its comparative pharmacodynamic, pharmacokinetic and clinical study]. AB - The efficacy of dinitrosorbilong (DNL)--a new long-acting isosorbid dinitrate (IDN) preparation applied to the gum--was evaluated in 72 coronary patients with stable angina of effort. Repeated treadmill tests revealed antianginal effect of DNL exceeding 8 hours. The degree and duration of DNL action significantly surpassed those of conventional oral IDN tablets and of some other long-acting IDN preparations. The results of pharmacokinetic studies show that DNL bioavailability is 491 +/- 240% as compared to conventional oral IDN tablets. Regular 7-day DNL administration resulted in a significant decrease in the frequency of anginal attacks and in the daily consumption of nitroglycerin tablets as compared not only to the control period but also to the period of conventional IDN tablet therapy. PMID- 3099810 TI - [Epilepsy induced by penicillin in rabbits: comparative study of the anticonvulsant effects of diazepam and chlordesmethyldiazepam]. PMID- 3099814 TI - Immunochemical studies on phosphoglycerate kinase deficiency. AB - Antisera to normal erythrocyte and skeletal muscle PGK, raised in rabbits, were shown to cross-react with extracts from normal tissues and with extracts from a subject with PGK deficiency. Radial immunodiffusion, using the antisera raised against normal human PGK, was used to determine the amount of cross-reacting PGK protein present in extracts of several tissues from an affected subject. For all tissues tested, activity was only a small percentage of the PGK protein concentration. In particular, evidence for normal levels of protein in erythrocytes and myocardium was obtained. The results indicate that the deficiency is due to a structural mutation of the enzyme. PMID- 3099815 TI - Enzyme and drug delivery systems. PMID- 3099813 TI - The effects of pH, buffers, and fatty acid concentration on the incorporation of radioactive arachidonate into endogenous neuronal nuclear lipids. AB - Using neuronal nuclei (N1) isolated from cerebral cortices of 15-day-old rabbits the incorporation of [3H]arachidonate into N1 lipids was followed in vitro. Arachidonate was principally incorporated into triacylglycerol and phosphatidylinositol. When low concentrations (32 mM) of Tris-HC1 (pH 7.4) were used, rates of total arachidonate incorporation were small and phosphatidylinositol received the bulk (greater than 84%) of the arachidonate. When the concentration of Tris-HC1 (pH 7.4) or, in certain cases, the concentration of arachidonate was increased, there was a rise in total arachidonate incorporation into N1, with an increasing proportion of radioactivity entering triacylglycerol until it was the predominantly labelled lipid. Using other buffers (phosphate, imidazole, HEPES, pH 7.4), the shift from phosphatidylinositol to triacylglycerol as principal labelled lipid, with buffer concentration, was not as marked as with Tris-HC1 (pH 7.4). When the buffer concentration was maintained at 107 mM and the pH was lowered to 6.5, the three amine-containing buffers showed a sizeable decline in arachidonate incorporation into N1 lipids and a corresponding decrease in triacylglycerol labelling. The proportion of the total radioactivity in N1 phosphatidylinositol rose as the pH declined. Of the buffers used, Tris-HC1 showed the greatest changes over the pH range. Based upon pK values for the amine buffers, it is suggested that an increased proportion of the protonated amine may be inhibitory to arachidonate incorporation in N1. Studies of acyl-CoA synthetase in N1 indicated this enzyme as the site of the inhibition. PMID- 3099812 TI - Arachidonic acid metabolites during nasal challenge. AB - In order to assess the role of arachidonic acid metabolites in the early reaction to antigen, we challenged six allergic individuals with and without premedication with aspirin and recorded their clinical response, as indicated by number of sneezes, and measured the levels of inflammatory mediators. The early reaction to antigen was associated with increases in the levels of histamine, N-alpha-tosyl-L arginine methyl esterase (TAME-esterase) activity, prostaglandin (PG) D2, leukotriene C4, PGE, and thromboxane. Aspirin significantly inhibited the increases in the cyclooxygenase metabolites PGE, PGD2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane but did not affect the amount of sneezing or the levels of histamine, TAME-esterase activity, or leukotrienes. The pattern of the metabolites and their response to pretreatment with aspirin parallel the response of purified human lung mast cells, supporting the notion that the early phase of allergic rhinitis is a mast cell-dominated event. PMID- 3099818 TI - Glyceryl trinitrate absorption: chewing versus sublingual administration. PMID- 3099817 TI - The acute inflammatory response to myocardial infarction: imaging with indium-111 labelled autologous neutrophils. AB - The uptake of indium-111 labelled neutrophils was examined in 30 patients with acute myocardial infarction by planar imaging and single photon emission computed tomography. The time from venepuncture to reinjection of the autologous labelled neutrophils was less than 2.5 hours and imaging was carried out 24 hours later. Twenty three patients had a positive uptake of neutrophils in the myocardium and imaging was improved by single photon emission computed tomography. There was a significant difference between the intervals from the onset of chest pain to injection of labelled neutrophils between patients with positive and negative images; early reinjection was more likely to produce a positive image. Indeed, all nine patients reinjected within 18 hours of the onset of symptoms had positive images. The results suggest that the stimulus for activation and migration of neutrophils is transient; this is an important factor if neutrophil release products play a role in cell damage after coronary occlusion. PMID- 3099819 TI - Variations in exposure to mitomycin C in an in vitro colony-forming assay. AB - The effect of mitomycin C on two human ovarian cancer cell lines was measured during several exposure times and concentrations using the Human Tumour Colony forming Assay (HTCA). Changes in exposure time and concentration resulted in considerable differences in tumour cell survival. It is concluded that several exposure times and concentrations are necessary for in vitro sensitivity testing. We suggest alternative criteria derived from pharmacokinetic data in patients instead of one-tenth of the peak plasma level which is the usual practice. PMID- 3099820 TI - Epidemiological investigations on neuroblastomas in Denmark 1943-1980. AB - During the period 1943-1980 a significant increase in the incidence of neuroblastoma was seen in Denmark. The incidence increased from a level corresponding to that in Finland to a level corresponding to that in the USA, and the increase appears to be continuing. The increase relates to children aged under 5 years, and is most pronounced in infants under 1 year. The incidence in the first year of life has, however, not yet reached the level of the USA. The increase in incidence is most likely a result of improved diagnosis, changes in the social composition of the population, and an increase in environmental carcinogens of importance in the induction of neuroblastomas. The incidence is lower in children of self-employed parents, and higher in infants of mothers aged under 20 or over 34 years. Aside from lower socio-economic circumstances for mothers under 20 years, no specific risk factors were revealed in this study. The observations of a family in which the mother has ganglioneuroma and both daughters have developed neuroblastoma, of a child who suffered from both neuroblastoma and neurofibromatosis von Recklinghausen, and of a significantly higher frequency of infants with signs of multicentric tumours in the offspring of mothers aged under 20 and over 34 years of age, is consistent with the two-hit theory of Knudson et al. (1972). PMID- 3099821 TI - Metabolic induction of experimental ulcerative colitis by inhibition of fatty acid oxidation. AB - There is some evidence that failure of fatty acid or beta-oxidation in the epithelium of the colonic mucosa is associated with the development of ulcerative colitis. We tested the hypothesis that inhibition of fatty acid oxidation in the colonic mucosa of the rat reproduces the histological, clinical and biochemical lesions of acute ulcerative colitis of man. A specific inhibitor of beta oxidation, sodium 2-bromo-octanoate, was instilled rectally for 5 days or exposed to isolated colonic epithelial cells which were subsequently tested for their ability to beta-oxidize n-butyrate. Weight loss, bloody diarrhoea and histological lesions occurred with 2-bromo-octanoate treated rats but not control animals. Ketogenesis and 14CO2 production was inhibited by 2-bromo-octanoate. Of 12 animals mucosal ulceration developed in six out of eight surviving animals and in all four animals that died. Ulceration, mucus cell depletion, vessel dilatation and increases of inflammatory cells were the most prominent histological changes. Present observations indicate that inhibition of beta oxidation produces acute colitis and suggests that inhibition of beta-oxidation is primary rather than secondary in the genesis of ulcerative colitis. A search for agents producing such biochemical lesions in man should be undertaken. PMID- 3099816 TI - 'Fissure sealants: Report of the Joint BDA/DHSS Working Party. PMID- 3099823 TI - Inhibition of growth of Listeria monocytogenes in vitro, by immunologically activated mouse resident macrophages. AB - Resident peritoneal macrophages, spleen macrophages and Kupffer cells isolated from normal CBA mice were treated with supernatants from spleen cells of normal or immunized mice, and cultured in the presence of heat-killed Listeria monocytogenes. The capacity of the macrophages, infected in vitro, to control the growth of Listeria was tested. In macrophages treated with supernatant from normal spleen cells, the organisms multiplied extensively during 24 h but in those treated with supernatant from immune spleen cells, growth was greatly inhibited. Macrophages isolated from mice irradiated with 8-9.5 Gy and treated with immune spleen cell supernatant, were as efficient or even more than those from unirradiated mice. The use of multispot slides proved to be a convenient and economical means of culturing and examining cells. PMID- 3099824 TI - Formation of granulomas in liver of silica-treated rats. AB - Hepatic silicosis was induced in rats by an intravenous injection of saline suspended silica, 40 mg/kg of body weight. Changes in the liver were examined by biochemical, histological and histochemical methods. Infiltration of the liver parenchyma by polymorphonuclear leucocytes was observed only on the first day after silica treatment. Formation of silicotic nodules began on the first day by clustering of liver macrophages. A 22% increase in liver weight and a 67% increase in total liver DNA reflected accumulation of cells in the liver by day 28 after silica injection. Local cell division contributed to this increase. Almost all cells in the nodules contained carbon when the rats had been given ink before silica. Macrophages showed high activity of lysosomal esterases on the first few days after silica treatment; the activity disappeared later. Large granulomas containing hundreds of cells including lymphocytes were seen 226 days after treatment. Hydroxyproline content per gram of liver tissue increased by 35% and 58% by day 80 and 162, respectively. Connective tissue formed capsules around the nodules and grew to their inside. Activities of lysosomal enzymes, beta-D galactosidase and acid proteases, in serum were increased by 20% and 300%, respectively, 35 days after treatment. Neither malondialdehyde concentration nor superoxide dismutase activity was elevated in silicotic liver. PMID- 3099825 TI - Nicotine alters fibronectin and factor VIII/vWF in human vascular endothelial cells. AB - Primary cultured human endothelial cells derived from umbilical cord vein were exposed during the growth of the culture to medium containing nicotine at various concentrations (0.5-200 micrograms/ml). Patterns of cellular fibronectin and factor VIII/vWF were compared to control by immunofluorescence technique. The levels of glycoproteins released in the culture medium were quantified by ELISA method. Treated cells showed an important decrease in fibronectin content with fragmentation of the fibronectin pericellular filaments, whereas the levels of secreted fibronectin were reduced in a dose-dependent manner. This reduction of fibronectin availability was correlated with an elongation of cell shape as revealed with phase contrast microscopy. By immunofluorescence, factor VIII/vWF cytoplasmic granules appeared drastically reduced whereas the secretion of the protein was significantly increased. As shown by electron microscopy, there was a concomitant reduction in the number and size of Weibel-Palade bodies. These studies indicate that nicotine modifies fibronectin and factor VIII/vWF distributions but in different ways. PMID- 3099822 TI - Enhanced thermal stability of lysosomal beta-D-galactosidase in parenchymal cells of tumour bearing mice. AB - The thermal stability of the enzyme beta-D-galactosidase varies among different organs in normal C57Bl/6 mice, and increases in the same organs in mice with Lewis Lung carcinoma. Thermal stability of this enzyme is also increased by treatment of the mice with cell-free extracts of tumour cells or with inflammatory compounds such as carrageenan or orosomucoid. After desialylation, orosomucoid more effectively increases the heat stability of the enzyme. By contrast talc, which has no galactosyl groups, is without effect on the stability of the enzyme in vivo. Macrophages of tumour bearing mice release into the culture medium a more heat resistant enzyme than macrophages from control mice. In both cases the heat resistance of the secreted enzyme is higher when fetal calf serum is present in the culture medium. Bovine serum does not modify the thermal stability of beta-D-galactosidase in this system. Incubation of lysosomal fractions of various organs with the synthetic beta-D-galactosidase substrate, p nitrophenyl-galactopyranoside, also strongly increases the heat resistance of the enzyme. The results suggest that one factor influencing the heat resistance of this enzyme may be complex formation between the enzyme and its substrates, an example of substrate protection of the enzyme. This may not be the only factor involved in enzyme stabilization in vivo. PMID- 3099827 TI - The incidence, clonal origin and secretory nature of serum paraproteins in chronic lymphocytic leukaemia. AB - Immuno-isoelectric focusing (IIEF) showed a 61% incidence of serum paraproteinaemia in 56 patients with chronic lymphocytic leukaemia (CLL). A strong correlation between the serum paraprotein heavy chain isotypes and those of the cytoplasmic heavy chain immunoglobulins was observed with no discrepancy noted in light chain expression. Density gradient ultracentrifugation analysis of selected sera containing monoclonal IgM showed that the IgM paraproteins were mostly 19S, secretory IgM but one patient was found to have both 19S and 8S monoclonal IgM. When the cellular origin of the IgM and IgD paraproteins found in one patient was investigated, both paraproteins were found to share the same idiotype and originate from the neoplastic clone. These findings confirm the view that there is an incomplete maturation block in chronic lymphocytic leukaemia and that in vivo secretion of paraproteins by the neoplastic cells is a relatively common occurrence. PMID- 3099828 TI - Clinical significance of positive platelet immunofluorescence test in thrombocytopenia. AB - The sensitivity and specificity of the platelet immunofluorescence test for the diagnosis of idiopathic thrombocytopenia (ITP) was studied in a series of 255 patients. Patients' platelets were tested directly. Diethyl-ether eluates of these platelets and patients' sera were tested indirectly with normal donor platelets. When all three tests were considered, positive results were obtained for 92.0% of the ITP patients with a platelet count of less than 150 X 10(9)/l and for 98.4% of the patients with a count of less than 100 X 10(9)/l. However, for many patients rather weak test results were obtained, with a score of 1/2-1 in 59.8% of the patients. Most patients (94.1%) with a positive direct test had a positive indirect test on the eluate. Thus, platelet-bound antibodies but not platelet-bound immune complexes were present in most, if not all, patients. Positive immunofluorescence tests were obtained for many patients with a diagnosis other than ITP. This resulted in a low specificity of the test for the diagnosis of ITP, evidently because autoimmune thrombocytopenia occurred together with many other diseases and also because antibodies against platelet cryptantigens (expressed by the action of EDTA or by platelet fixation) were present in many patients. PMID- 3099829 TI - Natural killer like cells in non-Hodgkin lymphomas. PMID- 3099826 TI - ABO and Rhesus phenotyping of fetal erythrocytes in the first trimester of pregnancy. AB - Determination of fetal red blood cell antigens in early pregnancy can be important in cases with a history of severe haemolytic disease of the newborn. From chorionic villus biopsies (CVB) between the 8th and 12th week of gestation a small number of fetal red blood cells was obtained, inevitably highly contaminated with maternal blood cells. Two techniques were used to demonstrate the minor (fetal) cell population with a blood group antigen differing from the major (maternal) cell population: a solid-phase microfluorescence technique (introduced in this paper) which was compared with the mixed agglutination technique. In series of artificial mixtures of erythrocytes it was shown that with the microfluorescence technique the ABO and Rhesus phenotypes of minor cell populations could be determined at a ratio of 1 in 4000 erythrocytes of the major population, making this technique 4 times as sensitive as the mixed agglutination technique. We further investigated the reliability of the microfluorescence technique to demonstrate antagonistic fetal blood groups in the first trimester of pregnancy. Of 18 women undergoing CVB prior to therapeutic abortion, blood group antagonism (ABO and Rhesus systems) was demonstrate in all 11 cases in which it was present. Therefore, it seems that CVB can be reliably used for the prenatal diagnosis of (recurrent) blood group antagonism. PMID- 3099830 TI - Topography of the high-affinity lysine binding site of plasminogen as defined with a specific antibody probe. AB - An antibody population that reacted with the high-affinity lysine binding site of human plasminogen was elicited by immunizing rabbits with an elastase degradation product containing kringles 1-3 (EDP I). This antibody was immunopurified by affinity chromatography on plasminogen-Sepharose and elution with 0.2 M 6 aminohexanoic acid. The eluted antibodies bound [125I]EDP I, [125I]Glu plasminogen, and [125I]Lys-plasminogen in radioimmunoassays, and binding of each ligand was at least 99% inhibited by 0.2 M 6-aminohexanoic acid. The concentrations for 50% inhibition of [125I]EDP I binding by tranexamic acid, 6 aminohexanoic acid, and lysine were 2.6, 46, and 1730 microM, respectively. Similar values were obtained with plasminogen and suggested that an unoccupied high-affinity lysine binding site was required for antibody recognition. The antiserum reacted exclusively with plasminogen derivatives containing the EDP I region (EDP I, Glu-plasminogen, Lys-plasminogen, and the plasmin heavy chain) and did not react with those lacking an EDP I region [miniplasminogen, the plasmin light chain or EDP II (kringle 4)] or with tissue plasminogen activator or prothrombin, which also contain kringles. By immunoblotting analyses, a chymotryptic degradation product of Mr 20,000 was derived from EDP I that retained reactivity with the antibody. The high-affinity lysine binding site was equally available to the antibody probe in Glu- and Lys-plasminogen and also appeared to be unoccupied in the plasmin-alpha 2-antiplasmin complex. alpha 2 Antiplasmin inhibited the binding of radiolabeled EDP I, Glu-plasminogen, or Lys plasminogen by the antiserum, suggesting that the recognized site is involved in the noncovalent interaction of the inhibitor with plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099831 TI - Changes in the coordination geometry of the active-site metal during catalysis of benzylpenicillin hydrolysis by Bacillus cereus beta-lactamase II. AB - Rapid-scanning stopped-flow spectroscopy (425-700 nm) has been used to study spectral changes in cobalt(II)-substituted Bacillus cereus beta-lactamase II during the binding and hydrolysis of benzylpenicillin. The experiments were carried out in aqueous solution over a temperature range of 3-20 degrees C. Three metallointermediates have been characterized by their visible absorption spectra. Two of them have visible absorption spectra identical with the intermediates ES1 and ES2 previously observed at subzero temperatures in a mixed aqueous/organic solvent [Bicknell, R., & Waley, S.G. (1985) Biochemistry 24, 6876-6887]. In addition, the branched kinetic pathway observed with the zinc(II) and cobalt(II) beta-lactamase II at subzero temperatures has been shown to occur with the cobalt(II)-substituted enzyme in aqueous solution at above-zero temperatures; thus, at pH 6.0 and 3 degrees C, the rate and equilibrium constants are readily determined for the reaction scheme: (Formula: see text). A third transient intermediate (called ES*) was found to precede ES1 in the pre-steady-state time period. The identity of the intermediates formed in aqueous solution with those previously observed in the cryostudy confirms that the mechanism is not changed either by the presence of an organic cosolvent or by subzero temperatures. Further characterization of ES1 and the steady-state intermediate ES2 at subzero temperatures, where their lifetime may be extended for up to several hours, has involved circular and magnetic circular dichroic studies. The magnetic circular dichroic spectra identify changes in the coordination sphere of the active-site metal during catalysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099832 TI - Localization of the free radical on the flavin mononucleotide of the air-stable semiquinone state of NADPH-cytochrome P-450 reductase using 31P NMR spectroscopy. AB - Microsomal NADPH-cytochrome P-450 reductase is the only mammalian flavoprotein known to contain both FAD and FMN as prosthetic groups. The discovery of the air stable semiquinone [Masters, B. S. S., Kamin, H., Gibson, Q. H., & Williams, C. H., Jr. (1965) J. Biol. Chem. 240, 921-931] and its identification as a one electron-reduced state [Iyanagi, T., & Mason, H. S. (1973) Biochemistry 12, 2297 2308] have engendered a number of studies to elucidate its unique catalytic mechanism. In this paper, 31P NMR spectroscopy is utilized to probe the localization of the free radical in this air-stable semiquinone form and to ascertain the environments of the FAD and FMN prosthetic groups as affected by the paramagnetic ion Mn(II). Consistent with conclusions drawn from studies utilizing FMN-free reductase [Vermilion, J. L., & Coon, M. J. (1978) J. Biol. Chem. 253, 8812-8819], the free radical was shown to reside on the FMN moiety by the broadening of its characteristic resonance in the 31P NMR spectrum. In addition, the effect of the paramagnetic ion Mn(II) was determined on the four resonances attributable to FAD and FMN and the additional ones contributed by NADP+ resulting from the oxidation of the physiological reductant NADPH. The addition of Mn(II) had little effect on the line widths of the FMN and FAD signals but resulted in an increase in their intensities due to a decrease in T1 relaxation times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099839 TI - Amino acid specific ADP-ribosylation: specific NAD: arginine mono-ADP ribosyltransferases associated with turkey erythrocyte nuclei and plasma membranes. AB - Turkey erythrocytes contain NAD:arginine mono-ADP-ribosyltransferases which, like cholera toxin and Escherichia coli heat-labile enterotoxin, catalyze the transfer of ADP-ribose from NAD to proteins, to arginine and other low molecular weight guanidino compounds, and to water. Two such ADP-ribosyltransferases, A and B, have been purified from turkey erythrocyte cytosol. To characterize further the class of NAD:arginine ADP-ribosyltransferases, the particulate fraction was examined; 40% of erythrocyte transferase activity was localized to the nucleus and cell membrane. Transferase activity in a salt extract of a thoroughly washed particulate preparation was purified 36,000-fold by sequential chromatography on phenyl-Sepharose, (carboxymethyl) cellulose, concanavalin A-Sepharose, and NAD agarose. Subsequent DNA-agarose chromatography separated two activities, termed transferases C and A', which were localized to the membrane and nucleus, respectively. Transferase C, the membrane-associated enzyme, was distinguished from the cytosolic enzymes by a relative insensitivity to salt and histone; transferase C was stimulated 2-fold by 300 mM NaCl in contrast to a 20-fold stimulation of transferase A and a 50% inhibition of transferase B. Similarly, histones, which stimulate transferase A 20-fold, enhanced transferase C activity only 2-fold. Transferase A', the nuclear enzyme, was retained on DNA-agarose. It was similar to transferase A in salt and histone sensitivity. Gel permeation chromatography showed slight molecular mass differences among the group of enzymes: A, 24,300 daltons (Da); B, 32,700 Da; C, and A', 25,500 Da. The affinities of transferase C for NAD and agmatine were similar to those of the cytosolic transferases A and B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099834 TI - Site-specific photo-cross-linking studies on interactions between troponin and tropomyosin and between subunits of troponin. AB - We have used the sulfhydryl-specific heterobifunctional photo-cross-linker 4 maleimidobenzophenone (BP-Mal) to study the interactions of rabbit skeletal tropomyosin with troponin and of the troponin subunits with each other. We found that alpha,alpha-tropomyosin specifically labeled at Cys-190 with BP-Mal photo cross-links with all three subunits of troponin with decreasing cross-linking yields in the order of troponin T, troponin I, and troponin C. There was no apparent Ca2+ dependence in the cross-linking yields. In separate experiments, we found that troponin C labeled specifically at Cys-98 with BP-Mal photo-cross links to both troponin I and troponin T in the two binary complexes, as well as in the ternary complex. Again, no Ca2+-dependent changes in the cross-linking yields were detectable. These results are in general agreement with the picture that troponin I and troponin T are in close contact with troponin C near its Cys 98 and that all three troponin subunits are in the proximity of Cys-190 of tropomyosin. PMID- 3099838 TI - Fluorescence quenching studies of apolipoprotein A-I in solution and in lipid protein complexes: protein dynamics. AB - Fluorescence lifetime and intensity quenching studies of human plasma apolipoprotein A-I (apo A-I) in aqueous solution and in recombinant lipoprotein complexes with dimyristoylphosphatidylcholine (DMPC) indicate differences in conformational dynamics. In aqueous solution, the bimolecular quenching constants (k*) for lipid-free apo A-I fluorescence quenching by oxygen and acrylamide are 2.4 X 10(9) and 0.38 X 10(9) M-1 s-1, respectively. These values are independent of the oligomeric form of the protein. There is no correlation between the relatively small k* for apo A-I, which reflects rapid, low-amplitude protein fluctuations, and the labile conformational changes of apo A-I folding reactions, like denaturation, which occur on a slower time scale. In recombinant DMPC/apo A I complexes (100:1 molar ratio) the protein increases in amphiphilic alpha helical structure as it blankets the lipid matrix. The apparent k* for oxygen quenching of apo A-I fluorescence in the complex is large and increases in a temperature-dependent manner. We have introduced a two-compartment model, which discriminates the source of quencher molecules as aqueous or lipid, to describe oxygen quenching of DMPC/apo A-I fluorescence. The magnitude and temperature dependence of the apparent k* predominantly reflect the partitioning of oxygen between the two phases rather than being a probe of the lipid physical state. Calculations of the helical hydrophobic moment in apo A-I indicate that tryptophan residues 8 and 72 occur at the lipid-protein interface of amphiphilic alpha-helices, whereas the other two tryptophan residues (50, 108) lie on the nonpolar faces of amphiphilic helices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099837 TI - Complete amino acid sequence of NADPH-cytochrome P-450 reductase from porcine hepatic microsomes. AB - The complete amino acid sequence of porcine hepatic microsomal NADPH-cytochrome P 450 reductase has been determined by microsequence analysis on several sets of proteolytic fragments. Sequence studies were performed initially on a 20 kilodalton (kDa) fragment and then on 80-kDa fragment. The amino-terminal end of the mature protein was blocked with an acetyl group, followed by 676 amino acid residues. It has been revealed that the COOH-terminal 20-kDa fragment has been derived from original enzyme by cleavage at the Asn-Gly (residues 502-503) linkage by an unknown mechanism. An NADPH-protected cysteine residue is located at residue 565, near a region exhibiting high sequence homology with ferredoxin NADP+ reductase. The FMN and FAD binding regions are possibly located in the amino-terminal region and the middle part of the protein molecule, respectively, as suggested by Porter and Kasper [Porter, T. D., & Kasper, C. B. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 973-977]. When this sequence is compared with that of rat enzyme, 60 amino acid residues are substituted, probably due to species differences. However, total sequence homology between these enzymes is 90%. Hydropathy plot analysis reveals that two regions from residues 27-43 and from residues 523-544 exhibit a high degree of hydrophobicity, suggesting membrane binding or interaction with cytochrome P-450. PMID- 3099840 TI - The mode of anchoring and precursor forms of sucrase-isomaltase and maltase glucoamylase in chicken intestinal brush-border membrane. Phylogenetic implications. AB - Chicken intestinal sucrase-isomaltase and maltase-glucoamylase have been isolated in their intact form by detergent solubilization and characterized as to their subunit composition and mode of anchoring in the brush-border membrane. Both are heterodimeric enzyme complexes composed of two subunits each of approximately 140 and 130 kDa. Contrary to the mammalian sucrase-isomaltase, chicken isomaltase was identified as the smaller of the two subunits. As was shown by hydrophobic labeling, only one of the two subunits in each heterodimer is anchored in the bilayer, the smaller 130 kDa isomaltase subunit of the sucrase-isomaltase complex, and the larger 140 kDa subunit of the maltase-glucoamylase complex. Both preparations contain a high-molecular weight polypeptide of approximately 250 kDa which in the case of sucrase-isomaltase could be identified by peptide mapping as a single-chain precursor not (yet) proteolytically processed to the final heterodimer. These first data on the mode of membrane anchoring of non-mammalian glycosidases indicate that they are synthesized, inserted into the membrane, and processed in ways similar to the mammalian enzymes. The fundamental unity between avian and mammalian sucrase-isomaltases suggests that the partial gene duplication of an ancestral isomaltase gene and the subsequent mutation of one of the active sites resulting in pro-sucrase-isomaltase has occurred prior to the separation of mammals from reptiles, i.e. more than 300 million years ago. PMID- 3099835 TI - Ether phosphatidylcholines: comparison of miscibility with ester phosphatidylcholines and sphingomyelin, vesicle fusion, and association with apolipoprotein A-I. AB - Nonhydrolyzable matrices of ether-linked phosphatidylcholines (PCs) and sphingomyelin have been used to study the mechanism of action of lipolytic enzymes. Since ether PCs, sphingomyelin, and ester PCs vary in the number of hydrogen bond donors and acceptors in the carbonyl region of the bilayer, we have examined several physical properties of ether PCs and sphingomyelin in model systems to validate their suitability as nonhydrolyzable lipid matrices. The intermolecular interactions of ether PCs with ester PCs, sphingomyelin, and cholesterol were investigated by differential scanning calorimetry. Phase diagrams constructed from the temperature dependence of the gel to liquid crystalline phase transition of 1,2-O-dihexadecyl-sn-glycero-3-phosphocholine (DPPC-ether) and 1,2-O-ditetradecyl-sn-glycero-3-phosphocholine (DMPC-ether) with both 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn glycero-3-phosphocholine (DPPC) demonstrated complete lipid miscibility in the gel and liquid-crystalline phases. Additionally, phase diagrams of egg yolk sphingomyelin (EYSM) with DMPC or DMPC-ether and 1,2-distearoyl-sn-glycero-3 phosphocholine (DSPC) or 1,2-O-dioctadecyl-sn-glycero-3-phosphocholine (DSPC ether) demonstrated no major differences in miscibility of EYSM in ester and ether PCs. The effect of 10 mol % cholesterol on the thermal transitions of mixtures of ester and ether PCs also indicates little preference of cholesterol for either lipid. The fusion of small single bilayer vesicles of DMPC, DMPC ether, DPPC, and DPPC-ether to larger aggregates as determined by gel filtration indicated that the ester PC vesicles were somewhat more stable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099833 TI - Dissociation and in vitro reconstitution of bovine liver uridine diphosphoglucose dehydrogenase. The paired subunit nature of the enzyme. AB - Uridine diphosphoglucose dehydrogenase (EC 1.1.1.22: UDPglucose dehydrogenase) at pH 5.5-7.8 is a stable homohexamer of 305 +/- 7 kDa that does not undergo concentration-dependent dissociation at enzyme concentrations greater than 5 micrograms/mL. Chemical cross-linking of the native enzyme at varying glutaraldehyde concentrations yields dimers, tetramers, and hexamers; at greater than 2% (w/v) glutaraldehyde, plateau values of 21% monomers, 16% dimers, 5% tetramers, and 58% hexamers are obtained. Dissociation at acid pH (pH 2.3) or in 4-6 M guanidine hydrochloride leads to inactive monomers (Mr 52,000). Denaturation at increasing guanidine hydrochloride concentration reveals separable unfolding steps suggesting the typical domain structure of dehydrogenases holds for the present enzyme. At greater than 4 M guanidine hydrochloride complete randomization of the polypeptide chains is observed after 10-min denaturation. Reconstitution of the native hexamer after dissociation/denaturation has been monitored by reactivation and glutaraldehyde fixation. The kinetics may be described in terms of a sequential uni-bimolecular model, governed by rate-determining folding and association steps at the monomer level. Trimeric intermediates do not appear in significant amounts. Reactivation is found to parallel hexamer formation. Structural changes during reconstitution (monitored by circular dichroism) are characterized by complex kinetics, indicating the rapid formation of "structured monomers" (with most of the native secondary structure) followed by slow "reshuffling" prior to subunit association. The final product of reconstitution is indistinguishable from the initial native enzyme. PMID- 3099841 TI - Electrophysiology of L-lysine entry across the brush-border membrane of Necturus intestine. AB - Microelectrode measurements of apical membrane potentials (Va) in absorptive cells of isolated Necturus intestine showed that, in the presence or absence of external Na+, 10 mM lysine added to the mucosal medium caused rapid depolarization followed by slower repolarization of Va. In Na+-free media the effects of 10 mM lysine on Va were abolished by 10 mM leucine which alone had no effect on Va under these conditions. This indicates that uncoupled electrodiffusion of lysine plays little or no role in lysine entry across the brush-border membrane. When external Na+ was greater than 10 mM the maximum depolarization of Va (delta Va') induced by [Lys] ranging from 5 to 30 mM was a simple saturable function of [Lys]. In Na+-free media, the relationship between delta Va' and [Lys] was biphasic. At first, delta Va' increased with increasing [Lys] reaching a maximum at 10 mM lysine. When [Lys] was further increased, delta Va' declined progressively to reach zero or near zero values. A single transport pathway model is proposed to account for rheogenic lysine entry across the brush border membrane in the presence and absence of Na+. This postulates an amino acid transporter in the membrane with two binding sites. One is an amino acid site specific for the alpha-amino-alpha-carboxyl group. The other is a Na+ site. Neutral amino acids (e.g. leucine) compete with lysine for the amino acid site. The Na+ site has some affinity for the epsilon-amino group of lysine. When external Na+ is high the Na+ site is essentially 'saturated' with Na+ and formation of a mobile complex between an amino acid and the transporter depends in a saturable fashion on amino acid concentration. In Na+-free media or in media containing low [Na+]; at low external [Lys] the epsilon-amino group of a lysine molecule (simultaneously attached to the amino acid site) interacts with the Na+ site to form a mobile complex, as external [Lys] is increased, attachment of different lysine molecules to each site of an increasing number of transporters to form nontransported or poorly transported complexes results in substrate inhibition of the rheogenic lysine transport process. PMID- 3099846 TI - Estimates of the rate of ligation during excision repair of ultraviolet-damaged DNA in mammalian cells. AB - When ultraviolet-irradiated mammalian cells are incubated with inhibitors of repair DNA synthesis, incomplete repair sites--seen as DNA breaks--accumulate. If the inhibition is reversed, the breaks are joined. Thus the ligation step of excision repair can be investigated. With aphidicolin as inhibitor, ligation occurs at up to 15-times the rate of incision. 3-Aminobenzamide (which inhibits poly(ADPribose) synthesis) does not delay the rejoining of DNA breaks. PMID- 3099842 TI - Modulation of Na+-Ca2+ exchange and Ca2+ permeability in cardiac sarcolemmal vesicles by doxylstearic acids. AB - We examine the effects of 5-, 12- and 16-doxylstearic acids on the Na+-Ca2+ exchange and passive Ca2+ permeability of cardiac sarcolemmal vesicles. Stearic acid is a weak stimulator of Na+-Ca2+ exchange. A doxyl moiety potentiates stimulation with the order of increasing potency being 5-, 12- and then 16 doxylstearic acid. Stearic acid has little effect on vesicle Ca2+ permeability but again the doxylstearates are more effective. The sequence of potency is reversed, however, from that for increasing Na+-Ca2+ exchange. 5-Doxylstearic acid most markedly exchanges passive Ca2+ flux followed by the 12-, and then 16 doxylstearic acids. Methyl esters of the doxylstearates have no effect on either Na+-Ca2+ exchange or Ca2+ permeability. We model the results as follows. For a fatty acid to stimulate Na+-Ca2+ exchange activity, an anionic charge is required to interact with the exchanger protein at the membrane surface. Stimulation is potentiated by a perturbation (such as provided by a doxyl group) within the lipid bilayer. The perturbation is most effective at a location towards the center of the bilayer. To increase passive Ca2+ permeability an anionic charge is again essential. Disorder within the bilayer is also important, but now the most important site is near the membrane surface. Results of experiments with linolenic and gamma-linolenic acid and previous studies with other fatty acids also support this model. PMID- 3099836 TI - Properties of two forms of DNA polymerase delta from calf thymus. AB - Purified calf thymus DNA polymerases delta I and II each have an associated 3' to 5' exonuclease but otherwise resemble DNA polymerase alpha in size, biochemical kinetic parameters, and the presence of DNA primase [Crute, J. J., Wahl, A. F., & Bambara, R. A. (1986) Biochemistry 25, 26-36]. Here we demonstrate a functional association of polymerase and exonuclease with each delta form. Furthermore, we show that the exonuclease can be dissociated from DNA polymerase delta I but does not appear to be removable from DNA polymerase delta II. Polymerases delta I, delta II, and alpha are equally sensitive to the inhibitor aphidicolin, suggesting a similarity in active site structure. In comparison with DNA polymerase alpha and delta II, DNA polymerase delta I has intermediate sensitivity to 2-(p-n-butylanilino)-2'-deoxyadenosine 5'-triphosphate (BuAdATP) or N2-(p-n-butylphenyl)-2'-deoxyguanosine 5'-triphosphate (BuPdGTP). The activity of the DNA primase of the delta II enzyme is insensitive to BuAdATP whereas 1.0 microM of this inhibitor will decrease the activity of the DNA primase of the alpha and delta I enzymes approximately 50%. Two monoclonal antibodies that potently inhibit DNA polymerase alpha are only slightly inhibitory to DNA polymerase delta I and are ineffective at inhibiting DNA polymerase delta II. DNA polymerase delta II had been previously found to be nearly inactive on nuclease treated calf thymus DNA, relative to its activity on homopolymeric DNA. We find that addition of purified calf histone proteins or spermidine can greatly enhance synthesis by this enzyme on activated calf DNA. PMID- 3099844 TI - Calcium-induced changes in permeability of dioleoylphosphatidylcholine model membranes containing bovine heart cardiolipin. AB - At calcium concentrations up to about 4 mM a selective permeability increase of cardiolipin/dioleoylphosphatidylcholine (50:50, mol%) membranes for calcium and its chelator arsenazo III is observed. Under these conditions calcium does not occupy all the binding sites of cardiolipin at the membrane interface and no vesicle-vesicle interactions are found. Lowering of the cardiolipin content of the vesicles to 20 mol% extends the calcium concentration range in which a selective permeability for calcium and arsenazo III is appearing up to about 12 mM. We suggest that the observed selective permeability increase is caused by transient formation of inverted micellar structures in the membrane with cardiolipin as translocating membrane component for calcium and arsenazo III. At calcium concentrations of 4 mM and higher for 50 mol% cardiolipin-containing vesicles a general permeability increase is found together with calcium cardiolipin binding in a 1:1 stoichiometry, vesicles aggregation and, above 8 mM of calcium, vesicle fusion. The loss of barrier function of the membrane under these conditions is correlated with vesicle aggregation and may be explained by a transition from a bilayer into a hexagonal HII organization of the phospholipids. PMID- 3099843 TI - Consequences of the interaction of calcium with dioleoylphosphatidate-containing model membranes: calcium-membrane and membrane-membrane interactions. AB - Calcium binds to dioleoylphosphatidate/dioleoylphosphatidylcholine (DOPA/DOPC) (20:80, mol%) multilamellar vesicles in the presence of a calcium ionophore with stoichiometry of about 0.6 nmol calcium per nmol phosphatidate and an apparent dissociation constant of about 1.7 mM. Experiments on the behaviour of monomolecular films at an air/water interface show that calcium-phosphatidate binding results in a decrease in the area of the polar region of the phosphatidate molecule, probably caused by headgroup dehydration and partial charge neutralization. At calcium concentration higher than about 3 mM calcium neutralizes the negatively charged membrane surface of DOPA/DOPC (20:80, mol%) large unilamellar vesicles, and vesicle aggregation is observed. At 10 mM of calcium this results in a low level of vesicle fusion. These observed processes are not attended with calcium-induced phosphatidylcholine transbilayer movement in the membranes of DOPA/DOPC (20:80, mol%) large unilamellar vesicles. When these findings are compared with the results of a previous study on the permeability behaviour of large unilamellar vesicles of the same phospholipid composition under comparable conditions (Smaal, E.B., Mandersloot, J.G., De Kruijff, B. and De Gier, J. (1986) Biochim. Biophys. Acta 860, 99-108) the following conclusions can be drawn. At low millimolar calcium concentrations (less than 2.5 mM) calcium does not occupy all the binding sites of the membrane, no membrane-membrane interactions are observed and a selective translocation of calcium and calcium-chelating anions is appearing. The mechanism of this translocation may be explained by the formation of uncharged dehydrated complexes of calcium, phosphatidate and calcium chelator, which can pass the membrane via transient occurring non-bilayer structures. Between 3 and 10 mM of calcium an a selective permeability increase of the vesicular membrane is found, which is not a consequence of vesicle fusion but apparently of vesicle aggregation, possibly causing packing defects in the membrane. PMID- 3099845 TI - Effect of pH on the kinetics of Na+-dependent phosphate transport in rat renal brush-border membranes. AB - The kinetics of Na+-dependent phosphate uptake in rat renal brush-border membrane vesicles were studied under zero-trans conditions at 37 degrees C and the effect of pH on the kinetic parameters was determined. When the pH was lowered it turned out to be increasingly difficult to estimate initial rates of phosphate uptake due to an increase in aspecific binding of phosphate to the brush border membrane. When EDTA or beta-glycerophosphate was added to the uptake medium this aspecific binding was markedly reduced. At pH 6.8, initial rates of phosphate uptake were measured between 0.01 and 3.0 mM phosphate in the presence of 100 mM Na+. Kinetic analysis resulted in a non-linear Eadie-Hofstee plot, compatible with two modes of transport: one major low-affinity system (Km approximately equal to 1.3 mM), high-capacity system (Vmax approximately equal to 1.1 nmol/s per mg protein) and one minor high-affinity (Km approximately equal to 0.03 mM), low-capacity system (Vmax approximately equal to 0.04 nmol/s per mg protein). Na+ dependent phosphate uptake studied far from initial rate conditions i.e. at 15 s, frequently observed in the literature, led to a dramatic decrease in the Vmax of the low-affinity system. When both the extra- and intravesicular pH were increased from 6.2 to 8.5, the Km value of the low-affinity system increased, but when divalent phosphate is considered to be the sole substrate for the low affinity system then the Km value is no longer pH dependent. In contrast, the Km value of the high-affinity system was not influenced by pH but the Vmax decreased dramatically when the pH is lowered from 8.5 to 6.2. These results suggest that the low-affinity, high-capacity system transports divalent divalent phosphate only while the high-affinity, low-capacity system may transport univalent as well as divalent phosphate. Raising medium sodium concentration from 100 to 250 mM increased Na+-dependent phosphate uptake significantly but the pH dependence of the phosphate transport was not influenced. This observation makes it rather unlikely that pH changes only affect the Na+ site of the Na+-dependent phosphate transport system. PMID- 3099847 TI - Characterization of serum apolipoprotein patterns in rats during suckling and post-weaning periods. AB - Changes of serum apolipoprotein patterns during the suckling and post-weaning periods were studied in rats. Concentrations of apolipoprotein A-IV and the high molecular-weight form of apolipoprotein B were markedly high during the early suckling periods and decreased at weaning. Secretion of apolipoprotein A-IV into the mesenteric lymph in 2-week-old rats was as high as that in adult rats into which the high-fat diet was infused constantly. Apolipoprotein A-IV was found both in high-density lipoprotein and lipoprotein-free fractions, and the relative distribution in the latter decreased developmentally. The concentration of apolipoprotein A-I was low for 1 week after birth, after which it increased to the adult level. The apolipoprotein E level during the suckling and post-weaning periods was similar to or above that of adult rats. The newly formed apolipoprotein B in very-low-density lipoproteins secreted by the isolated liver and by the primary culture hepatocytes of suckling rats was predominantly a high molecular-weight form. Overnight fasting and early weaning caused a remarkable alteration of the serum apolipoprotein profile. It therefore appears that frequent ingestion of dam's milk as well as ontogenic development are relevant to the serum apolipoprotein patterns characteristic for suckling rats. PMID- 3099848 TI - In vitro effects of alpha-bromopalmitate on metabolism of essential fatty acids studied in isolated rat hepatocytes: sex differences. AB - alpha-Bromopalmitate was shown to have a far more pronounced effect on metabolism of labelled linoleic acid (18:2, n-6) and arachidonic acid (20:4, n-6) in isolated liver cells from female rats than in those from males. alpha Bromopalmitate decreased triacylglycerol synthesis with a concomitant accumulation of fatty acid in diacylglycerol, indicating that the acylation of diacylglycerol is affected by alpha-bromopalmitate. PMID- 3099851 TI - UDPgalactose:glucosylceramide beta 1----4-galactosyltransferase activity in human proximal tubular cells from normal and familial hypercholesterolemic homozygotes. AB - The activity of a galactosyltransferase (GalT-2) that catalyzes the transfer of galactose from uridinediphosphogalactose to glucosylceramide in cultured normal human proximal tubular (PT) cells was characterized with respect to substrate saturation and metal ion requirements. Using a membrane-bound enzyme source, optimum activity was obtained in the presence of 1.0 mM Mn2+/Mg2+ (1:1) and a detergent mixture, Triton X-100/Cutscum (1:2, v/v), 0.1 mg/ml. The apparent Km values for glucosylceramide and UDP[14C]galactose were 3 microM and 0.5 microM, respectively. The Vmax values for glucosylceramide and UDP[U-14C]galactose were 0.12 nmol/mg protein per 2 h and 173 nmol/mg protein per 2 h, respectively. The purified 14C-labelled product comigrated with authentic lactosylceramide (LacCer) on TLC and HPLC analysis. The presence of a terminal beta-[14C]galactosyl group in the enzymatic product was proved by its cleavage (79%) by beta-galactosidase. Following the development of optimal assay conditions in normal PT cells, GalT-2 activity was next measured in urinary PT cells from homozygous familial hypercholesterolemic (FH) patients previously shown to accumulate large amounts of lactosylceramide. Urinary PT cells from familial hypercholesterolemic homozygous patients contained 35% higher GalT-2 activity as compared to control cells. We speculate that elevated GalT-2 activity may contribute to the storage of LacCer in FH-PT cells. PMID- 3099849 TI - Pathways of arachidonic acid liberation in thrombin and calcium ionophore A23187 stimulated human endothelial cells: respective roles of phospholipids and triacylglycerol and evidence for diacylglycerol generation from phosphatidylcholine. AB - Cultured endothelial cells from human umbilical vein were incubated for 20 h at 37 degrees C in the presence of [U-14C]arachidonic acid. Around 60-70% of the radioactive fatty acid was incorporated into cell lipids and was predominantly found in phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and triacylglycerol (39%, 33%, 13% and 6.5% of total incorporated radioactivity, respectively). Stimulation of the cells with human thrombin (2 U/ml) or calcium ionophore A23187 (5 microM) promoted the release into supernatants of arachidonic acid, 6-ketoprostaglandin F1 alpha, prostaglandins E2 and F2 alpha, in decreasing order of importance. The amount of secreted material was 4-fold higher with A23187, compared to thrombin. Parallel to the liberation process, phosphatidylcholine underwent a rapid decrease of radioactivity with both agonists, suggesting the involvement of a Ca2+-dependent phospholipase A2. Phosphatidylethanolamine displayed a minor decrease with A23187, whereas some reacylation was observed at 10 min with thrombin. Phosphatidylinositol was non significantly affected in thrombin-stimulated cells, whereas A23187 promoted an early but minor decrease, followed by resynthesis. In contrast to A23187, thrombin was also able to promote a significant hydrolysis of triacylglycerol, which might thus be implicated in the process of arachidonate liberation. Finally, radioactive phosphatidic acid and diacylglycerol appeared in endothelial cells, in response to the two agonists. However, diacylglycerol formation did not parallel that of phosphatidic acid, especially with A23187. Determination of the 14C/3H ratio of the different lipids upon cell labelling with both [14C]arachidonic acid and [3H]palmitic acid revealed that diacylglycerol and phosphatidic acid are hardly derived from inositol-phospholipid breakdown by phospholipase C. Other possible pathways involving for instance phospholipase C splitting of phosphatidylcholine are discussed. PMID- 3099850 TI - The role of polyamine reutilization in depletion of cellular stores of polyamines in non-proliferating tissues. AB - It was known from previous work that specific inhibition of neither ornithine decarboxylase activity nor polyamine oxidase activity produces spermidine depletion by more than 20% in non-growing organs, which are in a steady state with regard to polyamine metabolism. Combined treatment with inactivators of both ornithine decarboxylase and polyamine oxidase for a prolonged time caused, however, a gradual decrease of spermidine levels in liver, kidney and brain of mice by 50% and more. The method is in accordance with the previously suggested role of polyamine interconversion. Inhibition of polyamine oxidase prevents the reutilization for de novo polyamine biosynthesis of putrescine and spermidine, which are formed by oxidative splitting of N1-acetylspermine and N1 acetylspermidine, respectively, and the ornithine decarboxylase inhibitor prevents the compensatory increase of putrescine from ornithine. The findings are further evidence for the physiological significance of polyamine reutilization. PMID- 3099856 TI - [Differentiated effects of pH, pCO2 and protein concentration on the level of ionized calcium in the blood plasma and a computational algorithm for its standardized value]. PMID- 3099854 TI - Attenuation of postnatal hypoxia in the premature newborn rat by maternal treatment with dexamethasone: its relationship with lung phospholipid content. AB - The effect of maternal treatment with dexamethasone on blood PO2, PCO2, pH and lactate concentrations and on lung phospholipid content in premature newborn rats during the early neonatal period was studied. The postnatal hypoxia shown by premature newborn rats was prevented by this treatment. Postnatal hypercapnia was longer in premature newborns showed significantly lower lung phospholipid concentrations than term-delivered newborn animals. Maternal treatment with dexamethasone increased lung phospholipid concentrations which reached values close to those found in term newborns. Our results suggest that maternal treatment with dexamethasone prevents postnatal hypoxia in the premature newborn rat by increasing the lung phospholipid content, which results in an enhancement of oxygen transfer through the alveolar membranes and the attenuation of hyperlactiacidemia. PMID- 3099855 TI - [Effect of adaptation to hypoxia on the resistance of rats to the epileptogenic action of penicillin]. AB - The influence of adaptation to moderate hypoxia on anticonvulsive resistance of low tolerant rats has been investigated. Focal epilepsy was induced by penicillin application to sensorimotor cortex of the rat brain. Adaptation to hypoxia has been shown to increase the resistance of rats to epileptogenic penicillin effect which is manifested in the prolongation of the latent period of epileptiform discharges and less frequent epileptic fits. The mechanisms of the resistance increase remains to be investigated. PMID- 3099853 TI - [Separation and analysis of immunochemical properties of multiple forms of cytochrome P-450 from the rat liver]. AB - Four cytochromes P-450 induced by phenobarbital (PB-1--PB-4) and two cytochromes P-450 induced by S-methylcholanthrene (MC-1, MC-2) were purified to electrophoretic homogeneity from rat liver microsomes. The purification procedure involved sequential chromatography on n-aminooctyl-Sepharose 4B, DEAE-Sephacel and hydroxylapatite columns. The spectral and immunochemical properties of the cytochromes P-450 were estimated. All, but MC-1, cytochromes P-450 were found to exist in a low spin state. Using the Ouchterlony double diffusion method, it was shown that all cytochromes P-450 under study can be divided into two groups, i. e., PB-1--PB-2 and PB-3--PB-4, sharing common antigenic determinants inside the groups. High performance liquid chromatography of PB-3 and MC-2 on anion exchangers yielded two additional peaks from the PB-induced major cytochrome P 450 PB-3 and three peaks from the MC-induced major cytochrome P-450 MC-2. The multiplicity of cytochrome P-450 forms is discussed. PMID- 3099852 TI - The preparation of deglycosylated ricin by recombination of glycosidase-treated A and B-chains: effects of deglycosylation on toxicity and in vivo distribution. AB - Deglycosylation of ricin may be necessary to prevent the entrapment of antibody ricin conjugates in vivo by cells of the reticuloendothelial system which have receptors that recognise the oligosaccharide side chains on the A- and B-chains of the toxin. Carbohydrate-deficient ricin was therefore prepared by recombining the A-chain, which had been treated with alpha-mannosidase, with the B-chain, which had been treated with endoglycosidase H or alpha-mannosidase or both. By recombining treated and untreated chains, a series of ricin preparations was made having different carbohydrate moieties. The removal of carbohydrate from the B chain did not affect the ability of the toxin to agglutinate erythrocytes, and alpha-mannosidase treatment of the A-chain did not affect its ability to inactivate ribosomes. The toxicity of ricin to cells in culture was only reduced in those preparations containing B-chain that had been treated with alpha mannosidase, when a 75% decrease in toxicity was observed. The toxicity of the combined ricin preparation to mice varied from double to half that of native ricin, depending on the chain(s) treated and the enzymes used. Removal of carbohydrate greatly reduced the hepatic clearance of the toxin and the levels of toxin in the blood were correspondingly higher. These results suggest that antibody-ricin conjugates prepared from deglycosylated ricin would be cleared more slowly by the liver, inflict less liver damage, and have greater opportunity to reach their target. PMID- 3099857 TI - [Mechanism of the action of amino acids on gastric secretion]. AB - The experiments on dogs using gastrin inhibitors (Milid, secretin) and the data of radioimmunoassay on gastrin blood levels have shown that gastrin is not involved into the activation of gastric glands after parenteral injection of amino acids. PMID- 3099859 TI - Plasminogen activator inhibitors. PMID- 3099860 TI - Formation and functioning of the factor IXa-VIII complex on the surface of endothelial cells. AB - The formation and functioning of the factor X activating complex on the surface of cultured human venous endothelial cells (HVEC) were investigated. To the HVEC monolayer human factors IXa, VIII, X, CaCl2, and S-2222 were added, and a gradually increasing activation of factor X was observed. The maximum activity of 88 nmol/L Xa/min was reached after a 12-minute lag phase. In the presence of thrombin-activated factor VIII (VIIIt) the same maximum activity developed in eight minutes, which suggests that VIIIt accelerates the formation of the IXa VIII complex but does not influence its factor X-activating potential. Anti-VIII IgG did not affect the activity of the full-fledged complex. When anti-VIII IgG was added to the reaction mixture before factor VIII or during the lag phase of the reaction, it induced a concentration-dependent decrease of factor X activation. These results indicate that endothelial cells provide a binding surface for the IXa-VIII complex and that in the HVEC-bound complex factor VIII is protected from the effect of a specific antibody. However, the relatively slow development of the maximum activity indicates that HVEC only partially satisfy the surface criteria for the optimal assembly of the IXa-VIII complex. PMID- 3099862 TI - Comparative thrombolytic properties of single-chain forms of urokinase-type plasminogen activator. AB - The specific thrombolytic properties of urokinase and three molecular forms of single-chain urokinase-type plasminogen activator (scu-PA) were compared in a human plasma milieu in vitro and in an experimental thrombosis model in rabbits. These scu-PA molecules included Mr 54,000 scu-PA from human urine (urinary scu PA), scu-PA from conditioned media of a human lung adenocarcinoma cell line (CALU 3,ATCC,HTB-55) (cellular scu-PA) and an Mr 32,000 proteolytic derivative of cellular scu-PA (scu-PA-32k). All four molecular forms induced significant lysis of a 125I-labeled human plasma clot immersed in citrated human plasma at concentrations between 50 and 200 IU/mL. None of the four showed absolute fibrin specificity, but at equivalent lytic dose the three single-chain forms appeared to cause less fibrinogen degradation and alpha 2-antiplasmin consumption than two chain urokinase. In addition, the fibrinolytic potential of the three single chain forms was largely maintained during pre-incubation in plasma for up to 48 hours whereas that of urokinase was completely inhibited. Intravenous (IV) infusion of cellular scu-PA or scu-PA-32k into rabbits with a 125I-labeled thrombus in the jugular vein caused significant dose-dependent lysis at concentrations ranging from 8,700 to 35,000 and from 9,000 to 36,000 IU/kg respectively. Clot lysis was accompanied by minor alpha 2-antiplasmin consumption or fibrinogen breakdown. In contrast, urokinase induced lysis at doses between 20,000 and 200,000 IU/kg, but at higher doses was associated with significant systemic activation of the fibrinolytic system. It is concluded that scu-PA obtained from CALU-3 cell cultures has identical thrombolytic properties to that obtained from urine. In addition, the scu-PA-32k proteolytic derivative has the same fibrin-specific thrombolytic properties as the intact molecule. Cellular scu PA and scu-PA-32k may therefore constitute more readily available alternatives for clot-selective thrombolytic therapy in man. PMID- 3099858 TI - [Characteristics of the B subunit of a thermolabile Escherichia coli enterotoxin produced by the A-B+ E. coli strain]. AB - The preparation and identification of B subunit of thermolabile enterotoxin produced by A-B+ gene-containing strain are described. The E. coli strain studied is shown to produce protein identical in its molecular properties and antigenic specificity to B subunit obtained from the whole thermolabile enterotoxin. Partial antigenic affinity between B subunits of thermolabile enterotoxin obtained from different sources and B subunit from cholera enterotoxin has been established in immunochemical studies. Electrophoretic and immunochemical analysis has confirmed the absence of A-subunit admixtures in B-subunit preparation obtained from /A-B+/E. coli strain. PMID- 3099863 TI - Gamma-interferon in aplastic anemia: inability to detect significant levels in sera or demonstrate hematopoietic suppressing activity. AB - A radioimmunoassay (RIA) was used to quantitate biologically active gamma interferon (INF-gamma) in sera and in supernatants of cultured mononuclear cells obtained from 50 patients with aplastic anemia. Only five of the 50 serum samples had INF-gamma levels above background (greater than 0 less than 0.5 units per mL). Detectable levels of spontaneous INF-gamma (0.3 to 868 U/mL) were found in 18 of the 50 mononuclear cell supernatants tested. The addition of patient sera or INF-gamma positive supernatants to cultures of normal hematopoietic colonies did not result in reduced colony growth. Flow cytofluorimetric analysis of mononuclear cells failed to establish a correlation between the presence of INF gamma in supernatants and the number of activated T cells or natural killer (NK) cells in the mononuclear cell population. However, a significant correlation did exist between the presence of monocytes and the production of INF-gamma. Contrary to previous reports, our data suggest that patients with aplastic anemia do not have high circulating levels of INF-gamma. Unstimulated mononuclear cells from some patients will produce significant levels of INF-gamma, but this does not result in decreased in vitro hematopoiesis. PMID- 3099861 TI - Combinations of recombinant human interferons and retinoic acid synergistically induce differentiation of the human promyelocytic leukemia cell line HL-60. AB - The human acute promyelocytic leukemia cell line HL-60 is induced to differentiate into morphologically and functionally mature monocytelike cells by incubation with a combination of 10 nmol/L retinoic acid (RA) and various concentrations of recombinant immune interferon (rIFN-gamma). These induced cells show marked increases in antibody-dependent cellular cytotoxicity (ADCC), antibody-coated erythrocyte (EA) rosettes, nonspecific esterase, and 5' nucleotidase activity. rIFN-gamma alone at concentrations of 10 to 1,000 U/mL has essentially no effect on morphological maturation, nitroblue tetrazolium reduction, and immunophagocytosis. However, rIFN-gamma at these concentrations increases EA rosetting in a concentration-dependent manner that is not affected by 10 nmol/L RA. At a concentration of 1,000 U/ml, rIFN-gamma induces moderate increases in nonspecific esterase, 5'-nucleotidase, and ADCC. These parameters are markedly increased by the addition of 10 nM RA, a concentration which alone has no effect on these markers. Based on units of antiviral activity, rIFN-gamma is tenfold more active than rIFN-alpha D in inducing EA rosettes and 40-fold more active in inducing nitroblue tetrazolium reduction and immunophagocytosis. These results, indicating that combinations of rIFN-gamma or rIFN-alpha and RA synergistically induce differentiation of HL-60, suggest that this combination may have clinical utility in the treatment of patients with certain leukemias. PMID- 3099864 TI - Characterization of the Ss sialoglycoprotein and its antigens in Rhnull erythrocytes. AB - The Ss sialoglycoprotein (glycophorin B) and its antigens in Rhnull erythrocytes, which lack the Rhesus blood group antigens, due to apparently silent (amorphic type) or independent suppressor (regulator type) genes, were investigated. The quantity of the molecule in amorphic and in regulator type red cell membranes was found to be decreased by about 60%-70%, as judged from sodium-dodecylsulfate polyacrylamide gel electrophoresis. The Ss glycoprotein content in the erythrocytes from heterozygotes (regulator type) was diminished to an extent of about 30%. Confirming and extending previous studies, the S, s, Ux, Uz and 'N' antigens were slightly weakened in Rhnull erythrocytes. The U and Duclos receptors were only slightly or not depressed in amorphic Rhnull cells, but almost absent from or not detectable in those of the regulator type. This demonstrates that an additional alteration, apart from the decreased Ss glycoprotein content of the membranes, accounts for the weakness of these receptors in regulator type cells. We propose the hypothesis that (a) protein(s) encoded by the Rhesus locus form(s) a complex with the Ss glycoprotein. Thus, it (they) might facilitate the incorporation of the Ss glycoprotein into the membrane and also contribute to the complete expression of the U and Duclos antigens in normal cells. PMID- 3099867 TI - Organochlorine levels in edible marine organisms from Kuwaiti coastal waters. PMID- 3099868 TI - Polychlorinated biphenyls in honey bees. PMID- 3099870 TI - Alveolar efficiency for CO2 in normal people and patients with chronic obstructive lung disease. AB - A simple test is described which measures the efficiency of the lungs in removing CO2. The test, initially described by Cumming et al. [5, 9], has been simplified to make it suitable for use in routine pulmonary function test laboratories. Results from 50 normal subjects are compared with values obtained from 20 patients with chronic airway obstruction. The alveolar efficiency for removing carbon dioxide was clearly impaired in this group of patients. The test is very easy to perform, even for patients with quite severe lung disease, and has the advantage of providing an indirect measure of arterial PCO2. PMID- 3099869 TI - Effect of a simulated 3,048 meter altitude on the single-breath transfer factor. AB - The single-breath transfer factor (TLCO) was measured in ten healthy subjects at sea level and at a simulated altitude of 3,048 m. Measurements were made at sea level using 21% oxygen and at altitude using both 21% and 31% oxygen in the test gas. At 3,048 m altitude (PB = 69.7 kPa), the mean TLCO increased 14% or about 2.3% per kPa (0.3% per mmHg) decrease in inspired oxygen pressure. Our data also suggests that altering the test gas oxygen concentration to account for the change in PAO2 due to altitude results in a TLCO equivalent to that obtained at sea level. PMID- 3099865 TI - The effect of pretreatment with thio-TEPA and cytosine arabinoside on megakaryocytopoiesis in rats given a sublethal dose of thio-TEPA. AB - The present study was performed on rats, mainly to examine the so-called priming effect on megakaryocytopoiesis. One group of animals received 2 or 4 mg thio-TEPA or 200 mg cytosine arabinoside/kg body weight (the pretreatment) 2.5 days or 8 days prior to a dose of 10 mg thio-TEPA/kg body weight (the challenge dose). Another group received a pretreatment dose of 1 mg melphalan/kg body weight 2.5 days prior to a challenge dose of 3 mg melphalan/kg body weight. The number of bone marrow megakaryocytes, blood platelet production, mean platelet volume, blood platelet counts, leucocyte and granulocyte counts were examined on days 2, 4, 7, 10, 13, 16 and 20 after the challenge dose. The gut mucosa (number of mucosal crypts in terminal jejunum) and survival were studied in animals receiving pretreatment 2.5 days prior to a challenge dose of about LD100 for thio TEPA and melphalan. No systematic differences were observed whether the animals received pretreatment prior to the challenge dose or not. Thus, no priming effect was observed. PMID- 3099866 TI - Phenotype of chronic lymphocytic leukemia (CLL) B-cells. B-CLL cells express the Leu-8 antigen. AB - In the present report we studied the phenotype of peripheral blood mononuclear cells (PBMC) from 25 patients with B-cell chronic lymphocytic leukemia (CLL). Cells from all the cases expressed monoclonal surface immunoglobulins (SmIg), formed rosettes with mouse erythrocytes (MRFC) and were positive with OKB 2 and OKIa monoclonal antibodies. In addition, CCB 1 monoclonal antibody was positive in 17 out of 20, Leu-1 in 18 out of 21 and Leu-8 in 23 out of 25 cases. Double labelling experiments confirmed that the Leu-8 antigen was co-expressed on Leu 1+, CCB2+, HLA-DR+ B-CLL cells. Thus, B-CLL cells generally express the SmIg+, MRFC+, Leu-1+, OKB2+, Leu-8+ phenotype. Since it is known that normal peripheral blood B cells may be divided into two subpopulations according to Leu-8 expression, our data indicate that B-CLL cells originate from the more immature Leu-8+ B-cell subset which will respond to anti-IgM, whereas it reacts poorly to pokeweed mitogen. PMID- 3099873 TI - The importance of collateral portal veins for resistance to schistosomiasis in mice. AB - Mice with portal hypertension and collateral circulation caused by partial portal vein ligation yielded fewer worms than intact or sham-operated controls when infected with 50 Schistosoma mansoni cercariae for 8 weeks. The collateral circulation probably diverted arriving immature worms back to the general circulation where they died as the result of being out of their natural habitat rather than from immune killing. The present data strongly support the concept that a leaky portal system is the main factor in resistance to reinfection in murine schistosomiasis. PMID- 3099872 TI - Agglutination of sheep erythrocytes by Corynebacterium diphtheriae. AB - The hemagglutinating activity of 26 strains of Corynebacterium diphtheriae isolated from the upper respiratory tract and from skin lesions was determined using both a macro and a micro-technique. Six of the 26 strains tested were unable to agglutinate sheep erythrocytes. Furthermore there was a considerable variation in the hemagglutinating activity of the positive strains. PMID- 3099871 TI - Effect of adrenoceptor blockers on the acinar enlargement induced by Chagas' disease in the rat submandibular glands. AB - Chagas' disease induces acinar enlargement in the submandibular salivary gland of rats inoculated with the Y strain of Trypanosoma cruzi at the age of 27-28 days and killed 18 days after inoculation (acute phase). Propranolol, a beta adrenoceptor blocker, prevents the acinar enlargement induced by T. cruzi infection. Phenoxybenzamine, an alpha-adrenoceptor blocker, enhances this enlargement. These results suggest that catecholamines are involved in the genesis of the acinar hypertrophy induced by Chagas' disease. PMID- 3099874 TI - Three years of collaboration on the standardization of Chagas' disease serodiagnosis in the Americas: an appraisal. PMID- 3099878 TI - The prudent use of diagnostic ultrasound. British Institute of Radiology presidential address 1986. AB - Progress in diagnostic ultrasound is driven by the development of new technology. The place of new techniques in diagnostic algorithms has to be determined jointly by radiologists and clinicians and appropriate arrangements have to be made for training. About 30 million pounds per year is currently spent on diagnostic ultrasound in the UK. Diagnostic ultrasound depends on the information obtained as a result of ultrasonic irradiation of the patient. Biological effects, some of which are undesirable, can be produced by ultrasound but there is no evidence that the exposures used in diagnosis carry any risk. In judging whether ultrasonic scanning is appropriate in any particular situation, it is necessary to consider benefits, costs and available resources. The costs include not only the costs of the test but also the cost of any hypothetical ultrasonic hazard and the cost of misdiagnosis. The most prudent use of ultrasound is that which maximises the benefit-total-cost ratio and although this cannot presently be quantified, some of the concepts involved can be understood in terms of the health increment and the health decrement, the latter apparently being equal to zero when the diagnosis is correctly made using contemporary equipment. This approach can be extended to introduce the idea of profit arising from the test. As an example, obstetric ultrasound is considered to be appropriate when there is a medical indication for it. Although routine scanning at 16 weeks of pregnancy has been shown to result in a very large profit, there is still conflicting guidance about its advisability on the grounds of safety and existing accounting systems may restrict access to the profit. In discussing the desirability of ultrasonic scanning, patients can be informed that there is no reason to believe that there are any risks related to ultrasonic exposure. The imminent availability of inexpensive ultrasonic scanners for the layman is a worrying prospect to which the medical profession should now try to develop a prudent response. PMID- 3099875 TI - Effect of low intravenous doses of TRH, acid-TRH and cyclo(His-Pro) on cerebral and peripheral blood flows. AB - Local cerebral and peripheral blood flow in conscious and anaesthetized rabbits were investigated with the microsphere method, before and after the i.v. administration of 25 or 50 micrograms kg-1 thyrotropin-releasing hormone (TRH). Before the experiment, the cervical sympathetic chain was sectioned on one side in order to evaluate the possible effect of the sympathetic nerves on cranial and extracranial blood flows. Blood flow was also determined in anaesthetized rabbits before and after the administration of the TRH metabolites cyclo(His-Pro) and acid-TRH and after subsequent administration of 50 micrograms kg-1 TRH. TRH caused an increase in mean arterial blood pressure (MAP) of about 1 to 2 kPa whereas cyclo(His-Pro) and acid-TRH had no effect on MAP. In the anaesthetized animal an increase in total cerebral blood flow (CBFtot), from 71 +/- 7 to 107 +/ 12 g min-1 100 g-1 (P less than 0.05) was observed on the sympathetic intact side after 25 micrograms kg-1 TRH and a further increase to 130 +/- 9 g min-1 100g-1 (P less than 0.01) after 50 micrograms kg-1 TRH. A similar effect was observed on the sympathotomized side. An effect on CBF in the conscious animal was not detected. The control CBFtot (104 +/- 8 g min-1 100g-1) was higher in these animals than in the anaesthetized animals (P less than 0.02). Neither cyclo(His-Pro) nor acid-TRH mimicked the effect of TRH on CBF. In several peripheral tissues, e.g. skin, pancreas and gastric mucosa, a reduction in blood flow was noted after the administration of TRH in both anaesthetized and conscious rabbits. It was concluded that TRH can induce cerebral vasodilatation in animals with a depressed CBF, whereas the vasoconstrictor effect of TRH in peripheral organs is not markedly affected by the state of consciousness. PMID- 3099877 TI - Changes in cardiovascular sensitivity of alloxan-treated diabetic rats to arachidonic acid. AB - Arachidonic acid (AA, 0.125-2.0 mg kg-1) administered intravenously to male Wistar rats produced a dose-dependent fall in diastolic blood pressure. However AA (0.125-1.0 mg kg-1) injected into the autoperfused hindquarters via the aorta produced a dose-dependent increase in perfusion pressure. Both these responses to AA were inhibited by indomethacin (5 mg kg-1). The thromboxane A2 receptor antagonist AH23848 (5 mg kg-1, i.v.) inhibited pressor responses to AA in the autoperfused hindquarters, but potentiated depressor responses to AA (0.125-0.5 mg kg-1) in the whole animal. Alloxan-treated diabetic rats (14 days after a single s.c. injection of alloxan, 175 mg kg-1) displayed reduced sensitivity to the depressor effects of AA (1-2 mg kg-1) in the whole animal, increased sensitivity to the pressor effects of AA (0.5-1.0 mg kg-1) in the perfused hindquarters, and reduced sensitivity to the pressor effects of the thromboxane A2 mimetic U46619 (0.5-8.0 micrograms kg-1, i.a.) in the perfused hindquarters. These results suggest that AA can be predominantly converted to either pressor or depressor metabolites depending on the vasculature. In the diabetic state the ratio of the metabolites formed appears to change favouring a major pressor metabolite, which is probably thromboxane A2. PMID- 3099879 TI - Long-term management of patients who have had urinary diversions into colon. AB - Thirty-four patients with urinary-colonic diversions have been followed up for 13 to 41 years (mean 20.3). The commonest long-term complication was hyperchloraemic acidosis (50%). The most serious was neoplasm at the anastomotic site: benign lesions occurred in three patients and carcinomas in two (15%). Staining for sialomucins in colonic biopsies adjacent to the anastomoses was positive in 17 of 19 patients. It has been suggested that this represents a pre-malignant change. Analysis of faecal flora in 17 diverted patients and 27 controls revealed a significant difference in the carriage rate and viable count of Peptostreptococcus species. This finding has not been reported previously and the species could have a role in the aetiology of the neoplasms. PMID- 3099876 TI - The mechanisms by which haemoglobin inhibits the relaxation of rabbit aorta induced by nitrovasodilators, nitric oxide, or bovine retractor penis inhibitory factor. AB - The mechanisms by which haemoglobin and methaemoglobin inhibit the vasodilator actions of glyceryl trinitrate, sodium azide, nitric oxide, and the bovine retractor penis inhibitory factor (IF) were studied on rabbit endothelium-denuded aortic rings. Methaemoglobin was less effective than haemoglobin against each vasodilator, it was more effective at inhibiting the relaxation to azide than that to glyceryl trinitrate. Glyceryl trinitrate was neither bound nor inactivated when passed through columns of haemoglobin-agarose or methaemoglobin agarose. Azide was reversibly bound but less by haemoglobin-agarose than by methaemoglobin-agarose. Inhibition of the vasodilator actions of glyceryl trinitrate is not attributable therefore to a direct interaction with the haemoproteins, although a small part of the inhibition of azide-induced relaxation by methaemoglobin is likely to be due to a direct interaction. Columns of haemoglobin-agarose were more effective than columns of methaemoglobin-agarose in removing nitric oxide from solution. The greater ability of haemoglobin, compared to methaemoglobin, to inhibit vasodilatation induced by nitrovasodilators may therefore reflect the greater ability of haemoglobin to bind nitric oxide which is the active principle of the nitrovasodilators. Neither the acid-activated nor the inactive forms of IF were bound or inactivated when passed through columns of methaemoglobin-agarose. Neither form of IF was retained on passage through columns of haemoglobin-agarose, but the resulting activity in the eluates was less than control, was unstable and, unlike the original activity, decayed rapidly on ice. The greater ability of haemoglobin, compared to methaemoglobin, to inhibit vasodilatation induced by IF might therefore reflect the greater ability of haemoglobin to interact with this vasodilator and inactivate it. PMID- 3099881 TI - Superficial bladder cancer: intravesical chemotherapy and tumour progression to muscle invasion or metastases. AB - Of 299 patients who presented with superficial bladder cancer (Ta, T1), 60 were treated by intravesical chemotherapy (Epodyl, methotrexate or mitomycin C). The rate of tumour progression to muscle invasion or metastases was identical for each intravesical regime. There was no evidence that mitomycin C promoted tumour progression. Carcinoma in situ in non-tumour-bearing urothelium was the most significant predictive factor for progression to muscle invasion or metastases. PMID- 3099880 TI - Comparison of long-term monitoring and standard cystometry in chronic retention of urine. AB - Twenty-eight men with chronic retention of urine were investigated by means of a standard medium fill cystometrogram and by long-term monitoring of bladder pressure whilst the bladder filled naturally. Effective cystometric capacity was greater in each patient during standard cystometry (297 +/- 180 ml) than during long-term monitoring (99 +/- 100 ml; P less than 0.002). The incidence of detrusor instability was also greater during long-term monitoring than during standard cystometry (P less than 0.01). During filling, the detrusor pressure increased significantly both in standard cystometry (27.9 +/- 22.8 cmH2O; P less than 0.002) and in long-term monitoring (4.9 +/- 6.5 cmH2O; P less than 0.002). The detrusor pressure rise during filling was significantly greater during the standard cystometrogram than during long-term monitoring (P less than 0.002). Even when the detrusor pressure rise was corrected to take account of the different cystometric capacities this difference persisted (P less than 0.05). High end filling pressures are common in men with chronic retention investigated by means of a standard cystometrogram but are not observed during long-term monitoring. Such high pressures are probably due to the unphysiological rates of filling and the large volumes of fluid instilled during standard cystometry. PMID- 3099882 TI - The fate of the human testes following unilateral torsion of the spermatic cord. AB - In an attempt to explain the oligozoospermia commonly observed after unilateral testicular torsion, 56 patients with acute torsion were investigated prospectively. Blood was taken pre-operatively for antibody studies and a contralateral testicular biopsy was performed at the time of orchiopexy. At review 3 to 6 months post-operatively, late testicular atrophy was assessed and repeat antibody studies were performed together with a hormone profile and seminal analysis. Although the duration of torsion showed a close correlation with the degree of testicular atrophy (P less than 0.001), no such association could be demonstrated between duration of torsion and subsequent sperm concentration. Twenty of 35 patients had histological evidence of a pre-existing partial maturation arrest in spermatogenesis. Fifteen of 19 with the abnormality were oligozoospermic, while all of those with normal testicular histology had a sperm concentration within the normal range. Anti-sperm antibody formation following torsion was minimal and antitestis antibodies were absent. Testes prone to torsion already show impaired spermatogenesis. PMID- 3099884 TI - Big babies. PMID- 3099883 TI - Testicular schistosomiasis. PMID- 3099886 TI - The decline in the teaching of legal medicine. PMID- 3099885 TI - Carcinoma in situ of the testis. PMID- 3099887 TI - Dialysis arthropathy: amyloid or iron? AB - The clinical, biochemical, radiological, and pathological features in five cases of dialysis arthropathy were analysed. All patients were receiving long term haemodialysis and had had multiple blood transfusions. The arthropathy affected both large and small joints, was predominantly bilateral, and in all cases was associated with the carpal tunnel syndrome. In some instances joint pain was exacerbated during dialysis. In four cases the serum ferritin concentration was raised. Radiological examination showed a few juxta-articular cysts and erosions but most affected joints looked normal. All synovial tissue examined showed amyloid, which stained immunohistochemically for beta 2 microglobulin. Large amounts of iron were present in synovial tissue from affected joints. It is suggested that the deposits of iron, rather than amyloid, in synovial tissue may be the cause of the arthropathy. Iron may be derived locally as a result of haemarthrosis or it may be a manifestation of systemic iron overload. PMID- 3099888 TI - Endoscopic correction of primary vesicoureteric reflux: results in 94 ureters. AB - Sixty one patients with primary vesicoureteric reflux were treated by endoscopic injection of Mentor Polytef paste. Seventy six of the 94 treated ureters showed complete disappearance of vesicoureteric reflux after one injection. Eight refluxing ureters required a second injection, one required a third, and one a fourth. Six ureters showed improvement in the grade of reflux after the first injection. Two ureters did not show any change in the grade of reflux after endoscopic injection. The amount of paste injected to correct reflux in the 94 ureters varied from 0.1 to 1.0 ml (mean 0.33 ml). Patients were followed up for three to 25 months (mean 13.4 months). Follow up micturating cystograms in the 94 ureters showed absence of reflux in 83. Eleven ureters showed recurrence of reflux. Recurrence of reflux was attributed to early technical difficulties and to insufficient amounts of polytef paste used in some cases. Follow up urograms did not show evidence of ureteric obstruction in the treated ureters. Endoscopic injection of polytef paste is a safe, simple, and effective procedure for primary vesicoureteric reflux and averts the need for open operation. PMID- 3099889 TI - Isolated hypomagnesaemia presenting as focal seizures in diabetes mellitus. PMID- 3099890 TI - Mercury hazards arising from the repair of sphygmomanometers. PMID- 3099891 TI - The peak flow whistle: a simple device for monitoring peak flow in children. PMID- 3099892 TI - What is a good GP? PMID- 3099895 TI - Observations on the management of mood in a neurological hospital. PMID- 3099893 TI - Eating disorders in general practice. AB - A total of 748 patients who attended four south London group practices were screened using the eating attitudes test; 1% of women had bulimia nervosa and a further 3% a partial syndrome eating disorder. Eating and weight control behaviour and psychiatric indicators for an eating disorder were analysed. Patients with bulimia nervosa and partial syndromes were remarkably similar. They were mainly women, from the middle to upper classes, in the normal weight range but having had considerable weight fluctuation in the past, more likely to have had a history of menstrual irregularity, often psychologically troubled, and tended to have more family psychopathology. PMID- 3099894 TI - Prescribing in pregnancy. General principles. PMID- 3099896 TI - Urinary frequency and urgency. PMID- 3099897 TI - Foodborne disease surveillance in England and Wales 1984. Communicable Disease Surveillance Centre. PMID- 3099898 TI - The pill and breast cancer: why the uncertainty? PMID- 3099899 TI - Prolonged pregnancy: the management debate. PMID- 3099900 TI - Blood cyclosporin concentrations and renal allograft dysfunction. PMID- 3099901 TI - Treating ovarian cancer. PMID- 3099903 TI - Where should low weight babies be born? PMID- 3099902 TI - Glimpses of the mechanisms of hypertension. PMID- 3099904 TI - Metabolic abnormalities in children of non-insulin dependent diabetics. PMID- 3099905 TI - Use of the general health questionnaire in clinical work. PMID- 3099906 TI - Typing of Staphylococcus aureus resistant to methicillin. PMID- 3099907 TI - Humoral response to wheat protein in patients with celiac disease and enteropathy associated T cell lymphoma. PMID- 3099908 TI - Use and misuse of digoxin assay service. PMID- 3099909 TI - Adenosine: an importance beyond ATP. PMID- 3099910 TI - Primary pulmonary hypertension. PMID- 3099911 TI - Long live health promotion. PMID- 3099914 TI - Association between liberalization of Scotland's liquor licensing laws and admissions for self poisoning in West Fife. AB - Data were collected prospectively on 2868 consecutive patients admitted for self poisoning between 1971 and 1982. Analysis showed a dramatic increase in the frequency of alcohol taken in association with self poisoning, in both sexes, after the liberalization of Scotland's liquor licensing laws. This increase, however, did not appear to affect the severity of overdoses or the outcome. Total admission rates for self poisoning increased with relaxation of the liquor licensing laws, and since overdoses associated with alcohol tend to occur at night these impose considerable strain on casualty departments and acute admitting units. PMID- 3099913 TI - Corticosteroids and bone mass in asthma: comparisons with rheumatoid arthritis and polymyalgia rheumatica. AB - Bone mass has previously been shown to be reduced at peripheral bone sites in patients with bronchial asthma receiving corticosteroids. To assess whether total bone mass is reduced in asthma total body calcium was measured by in vivo neutron activation analysis in patients receiving various treatments for asthma and compared with results from normal controls and patients with rheumatoid arthritis and polymyalgia rheumatica. Compared with controls total body calcium was reduced by 13.6% (p less than 0.001) in patients with asthma receiving daily oral corticosteroids but by only 9.0% (p less than 0.005) in a similar group of patients who had received oral calcium supplements at the start of their corticosteroid treatment. Total body calcium was also reduced in a group of patients receiving only inhaled corticosteroids (8.8%; p less than 0.001) but not significantly reduced in a small group of patients with asthma who had never received these drugs. When compared with controls a group of patients matched for age and for dose of corticosteroids given for rheumatoid arthritis had a similar reduction in total body calcium to the patients with asthma receiving daily oral treatment (17.7%; p less than 0.001), but no such reduction was shown in patients with polymyalgia rheumatica. These findings suggest that the risk of bone loss with low dose oral corticosteroids in similar in asthma and rheumatoid arthritis. Further work is required to assess the clinical relevance of small losses of bone associated with the use of inhaled corticosteroids. PMID- 3099912 TI - Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS. AB - Sequential serum samples from 13 homosexual men who seroconverted for antibodies to human immunodeficiency virus (HIV) were tested for HIV antigen. In one of these men, who developed the acquired immune deficiency syndrome (AIDS), HIV antigenaemia preceded the onset of AIDS by more than a year and persisted throughout the course of the disease. This antigenaemia was accompanied by the disappearance of IgG antibody reactivity to the major HIV core protein p24. In none of the 12 others, who all remained without serious disease, were serum concentrations of HIV antigen detected, except on one occasion in one man. All their serum samples showed strong IgG antibody reactivity to p24. Nine children who were infected with HIV in 1981 by plasma transfusion from a single donor were also followed up for HIV antigenaemia. HIV antigen was almost constantly present in the serum (26 of 28 samples) of five children who developed AIDS related complex or AIDS and less often in the serum (four of 10 samples) of four children who remained free of symptoms. The two children who developed AIDS showed a virtual absence of antibody reactivity to p24. These results indicate that increased HIV gene expression is a contributing factor to the development of AIDS and also provide evidence for a switch from latent to active HIV infection. PMID- 3099915 TI - Do travel brochures give adequate advice on avoiding illness? PMID- 3099916 TI - Widespread use of condoms and low prevalence of sexually transmitted diseases in Danish non-drug addict prostitutes. PMID- 3099917 TI - Red cell antibodies and autoimmune haemolysis after treatment with azapropazone. PMID- 3099919 TI - Pyrexia of unknown origin and colorectal carcinoma. PMID- 3099918 TI - Phaeochromocytoma in the elderly: a poorly recognised entity? PMID- 3099920 TI - Beta blocker treatment for angina with associated bradycardia. PMID- 3099922 TI - Chronic urological problems in neurological patients. PMID- 3099921 TI - Eye disease at a community health centre. AB - A pilot study of eye disease was carried out over three months in a general practice at a London community health centre. During the study 223 patients with eye symptoms attended, representing 2.7% of all medical consultations and giving an annual consultation rate for eye disease of 57 per 1000 of the practice population. One hundred and sixty nine of these patients were seen by an ophthalmologist who diagnosed 43 different presenting disorders; seasonal allergic conjunctivitis accounted for 21% of these cases and other disorders of the lids and conjunctiva for 28%. The general practitioner's diagnoses were compared with the ophthalmologist's diagnoses in 30 cases; the principal differences were for specialist areas of external disease, medical retinal disorders, and where ophthalmic symptoms were unrelated to ocular abnormality. A cost analysis showed that an ophthalmic service in a community health centre would be cost effective by reducing attendances at the hospital outpatient department. PMID- 3099924 TI - Product liability comes closer. PMID- 3099923 TI - Prescribing in pregnancy. Identifying abnormalities. PMID- 3099925 TI - Contraception. PMID- 3099926 TI - Bias in awarding research grants. PMID- 3099927 TI - Effect of aspirin on pruritus. PMID- 3099928 TI - Clinical and bronchoscopic diagnosis of suspected pneumonia related to AIDS. PMID- 3099929 TI - Does breathing other people's tobacco smoke cause lung cancer? PMID- 3099930 TI - Pelvic pain in women. PMID- 3099931 TI - Recurring meningitis: beware the normal looking ear. PMID- 3099932 TI - Differences between neurological and neurosurgical approaches in the management of malignant brain tumours. PMID- 3099933 TI - Non-invasive femoropopliteal assessment: is that angiogram really necessary? PMID- 3099934 TI - Study of "discharge communications" from hospital. PMID- 3099935 TI - Plasminogen activators in human colorectal neoplasia. PMID- 3099936 TI - Primary care in the inner cities. PMID- 3099937 TI - Immunohistochemistry in lymphoma diagnosis. PMID- 3099938 TI - Man bites dog. PMID- 3099939 TI - Acyclovir update. PMID- 3099940 TI - The debasing of medicine in the Soviet Union. PMID- 3099941 TI - Imaging thrombus with radiolabelled monoclonal antibody to platelets. AB - Indium-111-hydroxyquinoline labelled platelets, though useful in the detection of thrombus, have not gained widespread use owing to the time and technical skill required for their preparation. A study was therefore conducted evaluating a new method of imaging thrombus with platelets radiolabelled with a 111In labelled monoclonal antibody, P256, directed to the platelet surface glycoprotein complex IIb/IIIa. When the number of receptors occupied by P256 was less than 3% of the total available on the platelet surface platelet function, as assessed by platelet aggregometry, was undisturbed. P256 was radiolabelled with 111In using diethylenetriaminepenta-acetic acid, which achieved a specific activity of 185 MBq (5 mCi)/mg. No impairment of immunoreactivity was detected at this specific activity. Platelets were labelled with radiolabelled monoclonal antibody in vitro in two patients at a receptor occupancy of 6% and in vivo--that is, by direct intravenous injection of P256--in six patients at a receptor occupancy of 1%. In vivo recovery and biodistribution kinetics suggested that after in vitro labelling platelets were minimally activated. The 111In kinetics recorded after intravenous P256 suggested rapid and efficient radiolabelling of platelets and gave no indication of platelet activation. Of the six patients who received intravenous P256, three had documented thrombus, two of whom gave positive results on P256 platelet scintigraphy. The third subject had chronic deep venous thrombosis and was scintigraphically negative. Imaging thrombus using a radiolabelled monoclonal antibody directed to platelets appears to offer great potential as a simple, non-invasive approach to the diagnosis of thrombosis. PMID- 3099942 TI - Cough response to citric acid aerosol in occasional smokers. AB - Twenty two normal women volunteers underwent a standard cough provocation test by inhaling solutions of citric acid of progressively increasing concentration. Eight were non-smokers, eight moderate smokers, and six occasional smokers. All the non-smokers and moderate smokers coughed. Moderate smokers tended to cough more than non-smokers, but not significantly so. None of the occasional smokers coughed at all (p less than 0.001). Possibly the ability to smoke occasionally with enjoyment is a marker for a diminished cough reflex. PMID- 3099943 TI - Oral acyclovir in acute herpes zoster. AB - Oral acyclovir at a dose of 800 mg five times daily for seven days was compared with placebo in a randomised double blind trial conducted at three centres in the United Kingdom. The study group comprised 205 elderly immune competent patients suffering from herpes zoster who were entered within 72 hours of the onset of rash. Acyclovir significantly reduced the times to arrest of new lesion formation (p = 0.005), loss of vesicles (p less than 0.001), and full crusting (p = 0.02) in those patients entered within 48 hours of the onset of rash. In addition, there was a significant reduction in pain during treatment with acyclovir as compared with placebo (p = 0.008). Of the patients with severe pain on entry, 40% (10/25) of those treated with acyclovir had no or only mild pain at the end of treatment, whereas in the placebo group all had residual moderate or severe pain (p less than 0.001). No clinically important adverse effects of acyclovir were reported. Oral acyclovir may modify acute herpes zoster and reduce pain. PMID- 3099944 TI - Chemoprophylaxis with oral amoxycillin against bacterial endocarditis: when should second doses be administered after dentistry? AB - The adequacy of serum bactericidal activity after oral amoxycillin given as prophylaxis against infective endocarditis was studied using a double blind randomised protocol in healthy volunteers having dentistry. One hour before their procedure 38 patients received 3 g amoxycillin syrup and 12 received matching placebo. Venous blood samples were drawn before and one and nine hours after dosing and serum amoxycillin concentrations determined using a standard bioassay. Samples containing amoxycillin had inhibitory titres measured against two reference isolates of viridans streptococci known to have caused infective endocarditis. The susceptibility to amoxycillin of one strain was high and the other low, respective minimal bactericidal and inhibitory concentrations being 0.08 and 0.04 mumol/l (0.03 and 0.015 microgram/ml) and 2.74 and 1.37 mumol/l (1 and 0.5 microgram/ml). Amoxycillin was detected in only post-treatment samples of patients given the active drug. There were no significant correlations between one or nine hour drug concentrations and age or physical characteristics, nor was there any relation to preceding food consumption. Correlations between drug concentrations at one and nine hours were weak (r = 0.34; p less than 0.05), but between corresponding drug concentrations and serum inhibitory titres there were consistent correlations (r = 0.46-0.48; p less than 0.005). Against the low susceptibility reference isolate bactericidal amoxycillin concentrations were encountered in only 20 of the 38 nine hour samples (95% confidence limits 34% and 66%). When repeat doses of amoxycillin are indicated after dentistry they should be given about four hours later, not eight hours later as commonly practised. PMID- 3099945 TI - Role of vagal neuropathy in the hyponatraemia of alcoholic cirrhosis. AB - The hyponatraemia common in decompensated cirrhosis arises in part from secretion of antidiuretic hormone attributed to a decrease in effective blood volume. Baroreceptors send inhibitory impulses to the midbrain and hypothalamus through the vagus and glossopharyngeal nerves. Since vagal neuropathy often occurs in chronic alcoholism, this might theoretically contribute to the inappropriate secretion of antidiuretic hormone, which might in turn induce hyponatraemia. In a prospective study including 34 patients with cirrhosis a high incidence of vagal neuropathy was found in the alcoholics (64%) and a clear cut increase in the incidence of hyponatraemia in patients with evidence of vagal damage and ascites (seven of eight patients (88%); p = 0.02). Results of a retrospective study of 64 patients with cirrhosis and ascitic decompensation showed hyponatraemia in 17 (50%) of 34 alcoholics but in only four (13%) of 30 patients with non-alcoholic disease (p = 0.006). Vagal neuropathy in alcoholic cirrhosis may contribute to the low serum sodium concentrations commonly found in these patients. PMID- 3099946 TI - Effectiveness of intravenous acyclovir in immunocompetent patient with herpes zoster encephalitis. PMID- 3099947 TI - Resolution of diabetic cheiroarthropathy. PMID- 3099948 TI - Alveolitis and haemolytic anaemia induced by azapropazone. PMID- 3099949 TI - Endocarditis prophylaxis: do patients remember advice and know what to do? PMID- 3099950 TI - Prevention of menstrual migraine by percutaneous oestradiol. PMID- 3099951 TI - What is a good GP? PMID- 3099952 TI - Value of case discussion groups in vocational training. PMID- 3099953 TI - Patient load and medical staffing in adult dialysis units in the United Kingdom. AB - A survey of medical staffing in 50 adult dialysis units in the United Kingdom in 1986 showed a wide range of patient to staff ratios or staffing score ratios. The total patient load (patients receiving haemodialysis in hospital and at home and those receiving continuous ambulatory peritoneal dialysis) varied from 12 to 270 per unit. Patients receiving acute haemodialysis or who had received a transplant were not included. The unit staffing score, on a weighted scale based on experience, varied from 6.0 to 40.5. Previous surveys have all been regionally or nationally based so criteria for assessing the adequacy of staffing in single units do not exist. This survey attempts to provide a guideline by describing the range of medical staffing compared with patient load in single dialysis units. No unit considered itself to be overstaffed, and several considered themselves to be greatly understaffed. Individual dialysis units should plead their own case in the light of their own circumstances and up to date information provided in nationwide staffing surveys such as this one. PMID- 3099954 TI - The abnormal cervical smear. PMID- 3099955 TI - Focal migraine and pregnancy. PMID- 3099957 TI - Are consultants accountable? PMID- 3099958 TI - What is a good GP? PMID- 3099956 TI - An assessment of the preregistration year experience. AB - All 115 graduates qualifying at Liverpool University Medical School in one year were sent a questionnaire in the final week of their preregistration year to assess the experience they had gained. Of the 105 graduates (92%) who replied, 99 (94%) considered the supervision that they had received to be adequate, 89 (85%) received most of their teaching from other junior doctors, and only 47 believed that they had learnt a considerable amount from their consultant colleagues. Half of the doctors received little or no training in terminal care. Although 100 (95%) felt competent in dealing with various medical emergencies, cardiopulmonary resuscitation skills were less developed; only 71 (68%) were confident in using a defibrillator, and 37 (35%) considered themselves to be competent in dealing with cardiac arrhythmias. A fifth of the doctors found interviewing relatives stressful. Of the 105 doctors who replied, 77 (73%) thought that their preregistration experience had had little or no effect on their choice of career. PMID- 3099959 TI - Procedures for obtaining informed consent. PMID- 3099960 TI - Effects of breast conservation on psychological morbidity. PMID- 3099961 TI - Time to scrap creatinine clearance? PMID- 3099962 TI - Respiratory symptoms and bronchial reactivity. PMID- 3099963 TI - Confusion after admission to hospital in elderly patients using benzodiazepines. PMID- 3099964 TI - Whooping cough immunisation for children with cerebral irritation or damage in the neonatal period. PMID- 3099965 TI - Relapse of duodenal ulcer. PMID- 3099966 TI - Randomised trial of treatment of hypertension in elderly patients in primary care. PMID- 3099967 TI - Blood cyclosporin concentrations and renal allograft dysfunction. PMID- 3099968 TI - Assessment of non-mydriatic photography in detection of diabetic retinopathy. PMID- 3099969 TI - Opposition to divulging patient information. PMID- 3099970 TI - Cost of anaesthetic drugs and clinical budgeting. PMID- 3099971 TI - 6-Hydroxydopamine lesion of the ventral noradrenergic bundle blocks the effect of amphetamine on hippocampal acetylcholine. AB - Rats treated with amphetamine exhibited an increase in hippocampal acetylcholine turnover, as determined by a mass fragmentographic technique. However, administration of amphetamine to rats which had received stereotaxically placed bilateral injections of 6-hydroxydopamine in the ventral noradrenergic bundle 10 days previously did not increase hippocampal acetylcholine turnover. Because the ventral noradrenergic bundle projects to the septal area, it is suggested that amphetamine increases acetylcholine turnover in the hippocampus by an action on noradrenergic neurons in this pathway. PMID- 3099972 TI - Reduction of cerebellar norepinephrine alters climbing fiber enhancement of mossy fiber input to the Purkinje cell. AB - Extra-cellular simple and complex spike activity from 58 Purkinje cells were recorded in cats that previously received an intracisternal injection of 6-OHDA which depletes brain catecholamines. The severest catecholamine depletion was noted for cerebellar norepinephrine (21.1% of controls). Less depletion occurred in the brainstem and the visual cortex. Past studies have shown that in normal non-depleted cats, somatosensory stimuli (forepaw tap) evoke both complex and simple spike responses. On those trials where complex spike or climbing fiber responses are evoked, there is an enhancement or increase in responsiveness in the majority of excitatory and inhibitory simple spike responses. In the norepinephrine depleted animal, there is a significant decrease in this climbing fiber enhancement only for the excitatory response components. Furthermore, on those trials where no complex spikes are evoked, there is a significant decrease in the excitatory but not in the inhibitory response amplitude. A slight but non significant increase in Purkinje cell background firing rate is also observed in the depleted animals. Thus, depletion of norepinephrine is associated with a reduction of both response amplitude and climbing fiber induced enhancement of excitatory simple spike responses. The inhibitory responses in these same cells are unchanged when compared to those recorded in the normal non-depleted animals. PMID- 3099973 TI - Immunocytochemical evidence for stimulatory control by the ventral noradrenergic bundle of parvocellular neurons of the paraventricular nucleus secreting corticotropin releasing hormone and vasopressin in rats. AB - The regulation, by catecholaminergic innervation, of parvocellular neurons of the paraventricular nuclei (PVN) secreting corticotropin releasing hormone (CRH) and vasopressin (Vp) was studied by immunocytochemical visualization of both neurohormones in control rats and in rats given discrete injections of 6 hydroxydopamine in the ventral noradrenergic ascending bundle (VNAB). In both groups, the changes in immunostaining intensities observed in axon terminals of the external median eminence and in PVN perikarya 48 h after a blockade of axoplasmic transport by intraventricular injections of colchicine, served as an index for hormonal release and synthesis. In controls, this treatment induced a strong decrease in CRH and Vp immunoreactivity within the terminals, together with intense labeling of PVN perikarya containing CRH. By contrast, bilateral VNAB lesions strikingly inhibited both the colchicine-induced reduction of the CRH and Vp immunoreactivity in axons and the accumulation of CRH in the perikarya. Unilateral VNAB lesions induced similar alterations but these were restricted to the ipsilateral PVN and median eminence. Comparison of these immunocytochemical data with earlier physiological observations on the effects of VNAB lesions on ACTH secretion indicates that the catecholaminergic afferents to the PVN conveyed by the VNAB stimulate the release and the synthesis of CRH and Vp by parvocellular neurons projecting into the external median eminence. PMID- 3099974 TI - The effects of pyridinium salts, structurally related compounds of 1-methyl-4 phenylpyridinium ion (MPP+), on tyrosine hydroxylation in rat striatal tissue slices. AB - We had previously reported that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces Parkinson's disease in humans and animals, inhibited tyrosine hydroxylation, the rate-limiting step of dopamine synthesis, in striatal tissue slices after its conversion to 1-methyl-4-phenylpyridinium ion by monoamine oxidase. In this report, structurally related compounds of 1-methyl-4 phenylpyridinium ion (MPP+) were synthesized and tested for their ability to inhibit tyrosine hydroxylation in rat striatal tissue slices. The following pyridinium salts showed inhibitory effect on tyrosine hydroxylation: pyridinium salts that substituted the alkyl group for the methyl group of MPP+ (1-ethyl-, 1 propyl-, 1-isopropyl-4-phenylpyridinium ions); pyridinium salts that changed the position of the phenyl group (1-methyl-2-phenyl-, 1-methyl-3-phenylpyridinium ions); pyridinium salts that modified the phenyl ring at 4 position (1-methyl-4 tolylpyridinium ion, 1-methyl-4-(4'-methoxyphenyl)pyridinium ion); and N methylisoquinolinium ion. In contrast, pyridinium salts in which the phenyl group was replaced with hydrogen, methyl or methoxycarbonyl group, paraquat (1,1' dimethyl-4,4'-dipyridinium chloride, one of bipyridinium compounds and a widely used herbicide), and N-methylquinolinium ion, showed no inhibitory effect. Nomifensine, an inhibitor of dopamine uptake, prevented the inhibition caused by 1-methyl-2-phenylpyridinium ion. The result suggests that the effective pyridinium salts are taken up into dopaminergic neurons likewise MPP+ by the dopamine transport system and inhibit tyrosine hydroxylation in striatal tissue slices. N-methylisoquinolinium ion could be one of the candidates of endogenous or environmental factors that produce Parkinson's disease. PMID- 3099975 TI - Selective lesioning of forebrain noradrenaline neurons at birth abolishes the improved maze learning performance induced by rearing in complex environment. AB - The effect of selective destruction of forebrain noradrenaline (NA) neurons induced by 6-hydroxydopamine (6-OHDA) at Day 1 after birth on Hebb-Williams maze performance was investigated in adult rats housed after weaning in a complex environment (EC) or an isolated (IC) environment for 35 days. Saline treated control rats raised in the EC made fewer errors than those raised in the IC. This effect of EC was completely abolished in 6-OHDA treated rats; for these animals no improved performance due to the housing condition was obtained. Protection of the NA neurons against 6-OHDA neurotoxicity by pretreatment with desipramine (DMI) resulted in an effect of EC identical to that seen in saline-treated controls. Postweaning housing in the IC led to an increased locomotion as compared to housing in EC, but this effect was not affected by neonatal 6-OHDA and/or DMI treatment. Neurochemical analysis confirmed cortical NA and metabolite depletion as well as a good protection by the DMI pretreatment. The present results indicate that central NA neurons are involved critically in mediating mainly the cognitive components of behavioral alterations induced by EC. PMID- 3099976 TI - Long-term effects of dopamine-depleting brain lesions on spontaneous activity of type II striatal neurons: relation to behavioral recovery. AB - The long-term effects of dopamine (DA)-depleting brain lesions on behavior and spontaneous activity of Type II striatal neurons were measured in rats after intraventricular injection of the neurotoxin 6-hydroxydopamine (6-OHDA). Spontaneous firing rates were increased relative to control values when recorded 4-8 days or 4-6 weeks postlesion in animals displaying aphagia, adipsia and akinesia. In contrast, spontaneous activity was not increased when recorded 4-6 weeks after the lesion in animals that had recovered from behavioral deficits. Other animals that had recovered from the effects of an earlier 6-OHDA treatment were given either a second injection of 6-OHDA or a systemic injection of haloperidol, a DA receptor antagonist. In both groups, discharge rates were elevated relative to control levels in association with a reinstatement of behavioral deficits. These results demonstrate that behavioral recovery after large DA-depleting brain lesions is associated with a return of spontaneous activity of striatal neurons to normal levels, and suggest that both behavioral and electrophysiological measures are dependent on the functioning of residual elements of the DA system. PMID- 3099977 TI - Estrogen-dependent effects of norepinephrine on hypothalamic gonadotropin releasing hormone release in the rabbit. AB - In the rabbit, either coitus or intraventricular administration of norepinephrine (NE) induces gonadotropin release and ovulation. It is hypothesized that ovulation induced with these manipulations involves activation of neuronal pathways that include catecholaminergic and peptidergic neurons. The aim of this study was to examine if perfusion of NE directly through the mediobasal hypothalamus (MBH) stimulates gonadotropin-releasing hormone (GnRH) release from the MBH in ovariectomized (OVEX) and estradiol-treated OVEX does (OVEX/E2). All does were fitted with push-pull (PP) cannulae directed to the MBH and subsequently subjected to PP perfusion at a flow rate of 20 microliters/min for 6 h to measure hypothalamic GnRH release. Five OVEX/E2 and 7 OVEX does received NE that was added to the PP system (intrahypothalamic NE perfusion) at the rate of 2.5 micrograms/min for 2 h during 6 h of PP perfusion. In addition, 6 OVEX/E2 does were given intrahypothalamic perfusion of homovanillic acid (HVA), a metabolite of the adrenergic system, to serve as controls. All PP samples were collected on ice at 10-min intervals, and jugular vein blood samples were obtained at 20-min intervals. The GnRH, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured by specific radioimmunoassays. In OVEX/E2 does, intrahypothalamic perfusion of NE, but not HVA, stimulated a 10-fold increase in peak values of hypothalamic GnRH within 30 min, and a 3-fold increase in peak values of plasma LH within 40 min. Thereafter, both GnRH and LH levels returned to basal values by the end of the NE perfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3099978 TI - Mnemonic correlates of unit activity in the hippocampus. AB - The role of the hippocampus in memory processing was examined by recording single unit activity while rats performed two different types of memory tasks. The same apparatus was used for all tasks; it consisted of two goal boxes, side by side, on the end of a runway. One goal box was white, the other was black. Experiment I used a working memory, delayed match-to-sample (DMTS) task. A trial began with a sample phase in which the rat was forced to a goal box containing a reward. The rat was then placed at the beginning of the runway again for the choice phase and allowed to enter either of the two goal boxes. Entering the goal box with the same color as that entered during the sample phase was rewarded. Experiment II used a within-subjects, within-units, design to test rats in two reference memory tasks, a cue task and a spatial task. During the cue task, the rat was rewarded for choosing the same colored goal box on each trial regardless of its spatial location. During the spatial task, the rat was rewarded for choosing the goal box in a specific location on each trial regardless of its color. During all tasks, the location of the goal boxes was changed between trials in a pseudorandom, counterbalanced fashion so that each colored goal box was on the right for half of the trials and on the left for half of the trials. During performance of the DMTS task, activity of most units was correlated with a combination of factors such as color and location, or color and phase. For example, most units showing differential activity in one of the colored goal boxes fired more when that box was in a certain spatial location, or during either the sample or choice phase. During performance of the reference memory tasks, the activity of most units was not correlated with behavior. However, the rate for some units changed between the cue and spatial tasks. When unit activity was correlated with behavior, it was dependent on a combination of dimensions such as color and spatial location. These results demonstrate that units in the hippocampus respond to combinations of stimulus dimensions such as color and spatial location, and to the temporal context necessary to solve a working memory task. PMID- 3099980 TI - [Quantitative structure-activity relations of the lethal effects of 38 halogenated compounds against Lepomis macrochirus]. AB - Autocorrelation molecular descriptors have been used for the prediction of acute toxicity (96 hrs., LC 50) of 38 halogenated compounds on Lepomis macrochirus (Teleostei-Centrarchidae). A stepwise regression procedure shows that structural and physico-chemical properties govern the ecotoxicological behaviour of these molecules. PMID- 3099979 TI - [Preliminary results in favor of the existence of a major surface antigen, specific for Leishmania braziliensis braziliensis]. AB - The comparative surface antigen study of 10 bolivian strains and 1 brazilian reference strain from L. b. braziliensis sub-species shows an important homogeneity within this group. All the strains tested so far present similar antigenic patterns with a major antigen at 72 kD. On the contrary, the comparative analysis of surface antigens of L. b. braziliensis with those of L. b. guyanensis, L. b. panamensis, L. mexicana amazonensis and L. donovani chagasi shows a large antigenic heterogeneity between the Leishmania sub-species and species we studied. The 72 kD antigen was only detected on L. b. braziliensis surface. PMID- 3099981 TI - [Lipolytic effects of 3-(hydroxymethyl)-N-methylpiperidine (4-chlorophenoxy) acetate HCl]. AB - Adding 3-hydroxymethyl N-methyl piperidine (4-chlorophenoxy) acetate, A, at increasing doses in the incubation medium leads to an increase in glycerol release from white adipocytes or brown adipose tissue. This stimulation is dose dependent and optimal with 10(-6) M. PMID- 3099982 TI - [Disjunction between the daily duration of light and the plasma level of prolactin under hyperlong days in rams]. AB - Adult rams were submitted to an artificial light regime with increasing and decreasing daylengths between 6 and 20 hrs. over a period of 8 months. Blood samples occurred at different durations of daylengths for measuring plasma levels of prolactin. Levels were high for a daily duration of light of 14.20, 17 and 18.30 hrs. along the increasing light-phase and of 18.30 hrs. during the decreasing light-phase. On the other hand prolactin levels were low for short daylengths, but also for a daylength of 20 hrs. It clearly appears that hyperlong days (greater than 18 hrs.) do not stimulate (or do actively inhibit) the secretion of prolactin in ovines. PMID- 3099983 TI - [Discrimination of the mother tongue by newborn infants]. AB - 4-day-old infants from French-speaking families were examined for their ability to discriminate French from Russian sentences. The infants gave evidence of discrimination as well as preference for French. PMID- 3099984 TI - [An enigmatic gestation in Ctenodactylus vali (Rodentia)]. AB - A parturition occurred in a female isolated since a duration longer than a gestation period. The most consistent hypothesis was the existence of sperm stocked inside the female and used for fertilization without the need of subsequent mating. PMID- 3099985 TI - [Active immunization of male pigs against gonadoliberin: effect on the secretion of gonadotropic hormones and on 5 alpha-androst-16-ene-one levels in adipose tissue]. AB - 27 boars aged 100 days were allocated to 3 experimental groups. The control group was untreated. The 2 other groups were given injections of LHRH, bound to BSA, with either Freund complete adjuvant or alumina gel. 4 immunisations were achieved at weekly intervals and a fifth injection was performed after 4 weeks. In animals treated with alumina gel, no specific antibodies were obtained. In the other hand, all 9 boars treated with FCA exhibited significant titers of specific anti-LHRH antibodies. In these animals, the neutralisation of blood LHRH induced a significant decline in both LH and FSH concentrations. Consequently, fat androstenone levels dropped dramatically, down to low levels, similar to those observed in surgically castrated males. PMID- 3099986 TI - [Compensation of the effects of shifts of anatomic positions of the heart on electrical tracings]. AB - The heart can take different anatomical orientations in the chest of various subjects and even in the same subject. The corresponding changes in perspective can deeply affect the electrical tracings recorded by fixed standardized leads. One same electrogenesis takes many appearances, complicating the analysis. Anatomically intrinsic tracings can be obtained with O. H. Schmitt's Resolver from a usual X, Y, Z lead system. Its moving trihaedral X'', Y'', Z'', has to be brought onto the heart's axis and septum. Being directly related to the heart, these tracings become independent of the heart's anatomical position in the chest. They show the electrical to anatomical topographic relations. However, they have not been in favour because Clinicians could not relate them to their usual rules of interpretation. This Note describes how to obtain normalized tracings that can benefit from the usual criteria of interpretation, as if shifted hearts were seen in an intermediate position. A constant opposite intermediate shift is applied to the three, X'', Y'', Z'', intrinsic components to restore an arbitrary normalized position. The new X'', Y'', Z'', components follow the moving trihaedral brought on the individual anatomical position measured by X rays and echocardiography. A heart being naturally in an intermediate position gives tracings as if no Resolver was in action. Compensated (or normalized) ECG's or isopotential maps can be similarly computed. PMID- 3099987 TI - [Demonstration of mating behavior in the field in the European fallow deer (Dama d. dama)]. AB - Adult males of a fallow deer population aggregate in a seasonal permanent rutting assembly. According to its spatial and behavioural characteristics, it is concluded that this assembly is a lek. PMID- 3099988 TI - [Protective effect of tumor necrosis factor (TNF) obtained by genetic recombination against experimental bacterial or fungal infection]. AB - Recombinant human tumor necrosis factor (rHuTNF) enhanced nonspecific resistance of mice to various bacterial and fungal infections, indicating that the protective effect previously reported by us with serum TNF (sTNF) prepared in mice, could be attributed to this macrophage-derived factor. Comparative assays with both TNF preparations have shown that the protection against the infections challenges was largely correlated with antitumor activity. The protective effect of the rHuTNF preparation, expressed from a cDNA clone in Escherichia coli, was not due to contaminating endotoxin products. Since recombinant TNF and sTNF have no direct bactericidal or anti-fungal activity, the enhanced resistance to infections can be explained by the action of TNF on macrophages and polymorphonuclear cells. The experimental data support the interpretation that TNF has an important role in nonspecific immunity. PMID- 3099989 TI - [Radioautographic and quantitative study of insulin binding sites in the rat brain]. AB - In the present study, we describe the specificity and the autoradiographic distribution of insulin binding sites in the rat central nervous system (CNS) after in vitro incubation of brain sections with [125I]-14A insulin. Increasing concentrations of unlabeled insulin produced a dose-dependent inhibition of [125I]-insulin binding which represented 92 +/- 2% displacement with 3 X 10(-5) M, whatever the brain sections tested. Half-maximum inhibition with native insulin was obtained with 2.2 X 10(-9) M, with 10(-7) M proinsulin whereas glucagon had no effect. Under our experimental conditions, no degradation of [125I]-insulin was observed. Autoradiograms obtained by apposition of LKB 3H Ultrofilm showed a widespread distribution of [125I]-insulin in rat CNS. However, quantitative analysis of the autoradiograms with 10(-10) M of labeled insulin, showed a high number of [125I]-insulin binding sites in the choroid plexus, olfactory areas, in both cerebral and cerebellar cortices, the amygdaloid complex and in the septum. In the hippocampal formation, the dorsal dentate gyrus and various subfields of CA1, CA2 and CA3 were labeled. Moreover, arcuate, dorso- and ventromedial nuclei of the hypothalamus contained high concentrations of [125I] insulin whereas a low density was observed in the mesencephalon. The metabolic role of insulin in the CNS is supported by the large distribution of insulin binding sites in the rat brain. However, the presence of high affinity binding sites in selective areas involved in perception and integrative processes as well as in the regulation of both feeding behavior and neuroendocrine functions, suggests a neuromodulatory role of insulin in the brain. PMID- 3099990 TI - [Difference in the maturation of the three-domain vasopressin precursor in the guinea-pig and rat: identification of a neurophysin-copeptin fragment in the guinea pig]. AB - Vasopressin, MSEL-neurophysin and copeptin have been isolated from guinea pig and rat neurophypophyses and their amino acid sequences have been determined. Whereas in rat processing of the three-domain precursor is complete, in the guinea pig a 132-residue fragment including MSEL-neurophysin and copeptin linked by an arginine residue has been characterized. This incomplete maturation (20% of the precursor) could be due to a deletion of an acidic residue in guinea pig copeptin when compared with other mammalian copeptins. PMID- 3099992 TI - Cancer statistics, 1987. PMID- 3099991 TI - [Characterization of a factor produced by human alloreactive T lymphocyte clones, active on the eosinophils and precursors of erythroid strains]. AB - Alloreactive T-cell clones obtained from cells infiltrating a human rejected kidney graft were shown to produce upon specific antigenic stimulation with interleukin 2, a factor triggering the proliferation of an interleukin 3 dependent murine cell line. The lymphokine responsible for this activity was a monomeric glycoprotein (MW = 41,000) exhibiting on one hand chemotactic as well as activating properties on murine and human eosinophils respectively, and on the other hand a burst promoting activity. Its biochemical and biological features strongly suggest that this factor cannot be likened to any known human lymphokine. PMID- 3099993 TI - Cancer clusters. PMID- 3099994 TI - Multicenter evaluation of training of non-endoscopists in 30-cm flexible sigmoidoscopy. AB - An estimated 145,000 patients will be diagnosed with colorectal cancer in the United States in 1987. Although half of these cancers are potentially detectable by sigmoidoscopy, rigid sigmoidoscopy is not widely used for early detection, largely because of discomfort it causes patients. Flexible sigmoidoscopy has been shown to be more acceptable and more efficient in detecting cancers. In order for flexible sigmoidoscopy to be of more value in cancer control, however, primary care physicians must learn the technique and incorporate it into their complete physical examinations. This paper reports the results of a multicenter trial that evaluated the training required for non-endoscopists to learn how to use the 30 cm flexible sigmoidoscope. Instructions with plastic models, followed by an average of six supervised patient examinations, proved sufficient for them to learn the necessary skills. PMID- 3099995 TI - Abusing children by smoking. PMID- 3099996 TI - Using mammography for cancer control: an unrealized potential. PMID- 3099998 TI - Ethics and cancer. PMID- 3099997 TI - Prevention of cancer of the oral cavity and pharynx. AB - Multiple environmental factors and a multistage pathogenic mechanism appear to be involved in oropharyngeal carcinogenesis. Tobacco and alcohol are the most important risk factors, but other agents may also contribute to malignant transformation. Individual susceptibility to environmental carcinogens, although significant, is still incompletely understood. Based on our present-day knowledge of risk factors, prevention should be possible in about two thirds of all oropharyngeal cancers. It cannot be achieved, however, without both public and professional education. A rational approach to prevention of oropharyngeal cancer should start in school before habits are formed, continued throughout adolescence, and reinforced in adults. Reduction or elimination of risk factors is of prime importance. For those who cannot quit tobacco, a reduction of tar content in cigarettes, cigars, pipes, and chewing tobacco, and elimination of nitrosamines, especially from smokeless tobacco, might also help to reduce risks. Control of chronic alcoholism is more difficult, but diet supplementation, especially with proteins, vitamins, and trace metals, would decrease the promoter effect of alcohol. Control of occupational risks is of less significance. The clinician must have a state-of-the-art understanding of all known risk factors for the prevention, early detection, and control of oropharyngeal cancer. The history should review in detail exposure to tobacco, alcohol, actinic radiation, and other agents. Age of first exposure or onset of habit; duration (years); quantity of tobacco smoked, chewed, or snuffed; and its relationship with the anatomic site at risk should all be precisely recorded. Exposure to alcohol or any other risk factor should be evaluated in the same way. This review has emphasized the relationship between the various risk factors and the site prevalence of malignant lesions. Habits, customs, and cultures, as well as anatomic physiologic factors, all have a bearing on the actual target sites at which the carcinogen(s) and promotor(s) are brought in contact with the oral mucosa. Habits and customs vary widely, both geographically and among individuals. Dentists and physicians should be aware of these individual factors as they examine their patients. PMID- 3099999 TI - Osteoclasts, mononuclear phagocytes, and physiological bone resorption. PMID- 3100000 TI - Effect of 1 alpha-hydroxycholecalciferol on psoriasis vulgaris: a pilot study. AB - We carried out a clinical trial of 1 alpha-hydroxycholecalciferol [1 alpha(OH)D3] at a dose of 1.0 microgram a day on 7 patients with psoriasis vulgaris. These patients had been treated by topical applications of corticosteroids before this study without improvement, and during the clinical trial, treatment of topical corticosteroids was continued on 6 of the 7 patients. Four of 7 patients showed complete remission and marked improvement and 2 additional patients showed minimal improvement of their skin lesions during and after the treatment with 1 alpha(OH)D3. No adverse reactions were noted during the treatment period. The mechanism of the phenomenon we observed has yet to be elucidated. Controlled trials of large numbers of patients with psoriasis vulgaris treated with 1 alpha(OH)D3 are under way. PMID- 3100001 TI - Alkaline phosphatase as a marker of osteoinductive cells. AB - Epithelial cells with osteoinductive potential (KB and WISH cell lines, transitional epithelium of several species) are rich in alkaline phosphatase activity. In contrast, cells devoid of osteoinductive ability are low in this enzyme activity. However, there were no differences between the two classes of cells with respect to acid phosphatase activity. PMID- 3100002 TI - Inhibition of bone cell metabolism increases strontium-85 uptake. AB - Experiments have been performed on the canine tibia to investigate whether perturbation of the energy metabolism of bone cells can influence the short-term exchange of bone mineral. Simultaneous injection of three radioactive tracers, 125I-albumin, 85Sr, and 86Rb, into the tibial nutrient artery was followed immediately by measurement of the concentration of these tracers in the venous outflow from the bone for a period of 5 minutes. This procedure was performed before and after the injection of potassium cyanide into the bone. From the measured concentrations, extraction ratios for 85Sr and 86Rb with respect to 125I albumin were calculated. It was found that net extraction after 5 minutes of 85Sr was significantly increased. This result indicates that efflux of ions from exchangeable mineral is dependent to a significant extent on the metabolic activity of bone cells. PMID- 3100003 TI - Bone modeling during growth: dynamic strain equilibrium in the chick tibiotarsus. AB - Bone loading was quantified, using in vivo strain recordings, in the tibiotarsus of growing chicks at 4, 8, 12, and 17 weeks of age. The animals were exercised on a treadmill at 35% of their maximum running speed for 15 minutes/day. In vivo bone strains were recorded at six sites on the tibiotarsus. Percentages of the bone's length and a percentage of top running speed were used to define functionally equivalent sites on the bone, and a consistent exercise level over the period of growth was studied. The pattern of bone strain defined in terms of strain magnitude, sign, and orientation remained unchanged from 4-17 weeks of age, a period when bone mass and length increased 10-fold and threefold, respectively. Our findings support the hypothesis that bones model (and remodel) during growth to achieve and maintain a similar distribution of dynamic strains at functionally equivalent sites. Because strain magnitude and sign (tensile versus compressive) differed among recording sites, these data also suggest that cellular responses to strain-mediated stimuli differ from site to site within a bone. PMID- 3100004 TI - Vitamin D3 and avian bone in vitro: stimulation of calcium movement into Japanese quail calvaria. AB - Addition of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) to cultured neonatal mouse calvaria has consistently led to bone resorption as determined by an increase in medium calcium. No such effect on avian bone has been widely reported. We have tested the in vitro effects of 1,25(OH)2D3 on 48- and 96-hour cultures of calvaria removed from both sexes of Japanese quail at various ages. No effect of 1,25(OH)2D3 on net calcium movement was seen in cultures of calvaria removed from neonatal (5-day), 1-week, and 2-week-old quail. In cultures of calvaria from 6 week-old female quail, addition of 1,25(OH)2D3 resulted in a fall in medium total and ionic calcium concentrations after 48 and 96 hours of incubation, indicating an uptake of calcium by the bones. A maximal effect was seen at 1 X 10(-7) M 1,25(OH)2D3. Bones removed from male and female quail showed no difference in response between the sexes. Bones removed from 5-, 4-, and 3-week-old male and female quail exhibited a progressively decreasing response with decreasing age. After 6 weeks of age female birds begin to exhibit hypercalcemia associated with reproductive activity. Bones removed from 7- and 8-week-old female quail responded to 1,25(OH)2D3 in a similar fashion whether they were hypercalcemic (7 weeks, 20.3 mg/dl; 8 weeks, 31.7 mg/dl), or normocalcemic (10.1 mg/dl). This stimulatory effect of 1,25(OH)2D3 on calcium uptake by avian bone is in sharp contrast to the hormone's effect in cultures of perinatal mammalian bones, which consistently respond to 1,25(OH)2D3 by releasing calcium into the medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100006 TI - Effects of salmon calcitonin in postmenopausal osteoporosis: a controlled double blind study. PMID- 3100005 TI - Production of a monoclonal antibody to enamelins which does not cross-react with amelogenins. AB - Developing enamel matrix contains a complex mixture of proteins whose characterization is essential to an understanding of amelogenesis. It is not known whether each component is the product of an individual gene, or whether they are interrelated by physiologic or artifactual breakdown. To define these relationships, monoclonal antibodies were prepared to enamel proteins and we have previously reported the characterization of six antibodies to amelogenins which did not react with enamelins (Christner et al. (1985) Arch. Oral Biol. 30:849 854). We now report the isolation of antibody to enamelins which stains the enamel matrix but does not cross-react with amelogenins. These results suggest that amelogenins and enamelins are distinct classes of proteins. PMID- 3100007 TI - Diltiazem dose responses in sustained therapy for stable angina pectoris. AB - Fifteen patients with stable effort angina were treated for 2 weeks with each of diltiazem 120 mg, 240 mg, 360 mg or placebo in a double-blind crossover protocol. The frequency of angina was decreased from 7.2 +/- 1.1 (mean +/- S.D.) episodes per 2 weeks with placebo to 5.9 +/- 5.2 (N.S.), 4.1 +/- 1.1 (p less than 0.01) and 1.5 +/- 0.8 (p less than 0.005) with 120 mg, 240 mg and 360 mg diltiazem respectively. Similar decreases occurred in nitroglycerin consumption. Ten hours after the last dose of each treatment period, each patient was challenged with 120 mg diltiazem. Treadmill exercise testing was carried out at 0, 1, 2, 4 and 8 hours. Time to onset of angina and 0.1m V ST depression increased at 1 hour, was maximal at 2 and 4 hours, and remained elevated at 8 hours. Two weeks of sustained treatment with diltiazem did not alter the responses in treadmill performance to 120 mg diltiazem. Hemodynamic changes were consistent with decreased myocardial oxygen demand and increased myocardial oxygen supply by diltiazem. There was no significant attenuation of hemodynamic response with sustained therapy. Trough plasma levels of diltiazem at 10 hours following the last dose of sustained therapy varied in a dose-dependent manner. However, corresponding exercise tolerances were identical regardless of the plasma level. Peak drug levels at 4 hours following 120 mg aldo did not correlate with exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100008 TI - Surgical ligation of patent ductus arteriosus in a neonatal intensive care setting is safe and cost effective. AB - The physiological and biochemical status of two groups of neonates with patent ductus arteriosus (PDA) requiring surgical ligation were compared. One group (n = 14) had ductus ligation in the operating room (OR) and the other group (n = 14) had the same operation in an isolation room in the Neonatal Intensive Care Unit (NICU). The groups were closely matched in terms of gestational age and weight. Nursing time and disposable equipment savings were significantly different. We have confirmed that PDA ligation can be done safely in the NICU and is more cost efficient than ligation in the OR. PMID- 3100010 TI - Economic evaluation of health services: more than dollars saved. PMID- 3100009 TI - 6-Hydroxydopamine treatment enhances excitation of cultured cerebellar neurons by glutamate. AB - Explant cultures containing identifiable cerebellar cortical neurons and locus coeruleus neurons were treated with 500 microM 6-hydroxydopamine. At this concentration, locus coeruleus neurons were usually degenerated after 48 h, while the cerebellar cortical neurons had a normal appearance. Extracellular recording and iontophoresis of noradrenaline and glutamate were used to test for changes in electrical activity or neurotransmitter responsiveness of the cerebellar neurons. At 4-5 days following the toxin exposure, spontaneous spiking activity appeared similar to that in control cultures. Mean iontophoretic currents required to give noradrenaline-induced depressions of activity were somewhat lower for the toxin treated cultures than for controls but not significantly so. The mean currents for glutamate excitations, however, were markedly lower in the treated cultures. Noradrenaline potentiations of glutamate responses were observed in both treated and control cultures. The greatly increased sensitivity of cerebellar neurons to glutamate does not seem related to degeneration of granule cells in the treated cultures but might be explained by disruption of astrocytic uptake mechanisms for glutamate. PMID- 3100011 TI - Partial gonadotrophin deficiency is infrequent in infertile men. AB - Hormone values and semen analyses were studied in 1761 men referred for evaluation of infertility to determine the frequency of isolated deficiency of either FSH, LH, or partial deficiency of both gonadotrophins. There were 17 men (1%) with oligospermia and FSH values at the lower end of the normal range. Without treatment, four pregnancies occurred in this group. Of the remainder, one was treated with gonadotrophin replacement therapy with no improvement in sperm concentration or motility. One man had possible isolated LH deficiency, but was subsequently found to have normal LH and testosterone values. No case of partial gonadotrophin deficiency was found. It was concluded that isolated deficiency of either FSH, LH, or partial deficiency of both gonadotrophins must be extremely rare as a cause of infertility. PMID- 3100012 TI - Reversible pituitary ovarian suppression induced by an LHRH agonist in the treatment of endometriosis--comparison of two dose regimens. AB - Buserelin [D-Ser(TBU)6-des Gly NH2(10) LHRH ethylamide], an LHRH agonist, was administered intranasally at two dose levels, 200 micrograms t.d.s or 300 micrograms t.d.s., to 20 women with proven endometriosis, many with recurrent disease. Both dose schedules achieved significant suppression of circulating 17 beta-oestradiol levels often to within the postmenopausal range, the larger dose inducing significantly greater suppression (P less than 0.05). Serum FSH values were suppressed below baseline but serum LH remained at pretreatment levels or above, whilst on treatment. Complete resolution of endometriotic deposits was achieved in 68% of cases following 6 months treatment with dramatic and long standing relief of symptoms with no apparent dose difference. In all other subjects there was significant reduction in the extent of endometriotic deposits and improvement in American Fertility Society classification of disease stage. The most commonly occurring side effect was hot flushes; their intensity and frequency related to the degree of suppression of serum oestradiol and the dose of Buserelin administered. PMID- 3100013 TI - Short-term chemotherapy of poor-prognosis metastatic breast cancer with three non cross resistant chemotherapy regimens. A Southwest Oncology Group Study. AB - A Southwest Oncology Group pilot study was designed to evaluate a brief, 4.5 month induction course of chemotherapy with three presumably non-cross resistant regimens in poor-prognosis metastatic breast cancer. Sixty-three patients were treated with doxorubicin, cyclophosphamide, plus vincristine on day 1, methotrexate followed 30 minutes later by 5-fluorouracil (5-FU) on day 22, and mitomycin C plus 3 days of vinblastine on day 43. All three sequential regimens were repeated once and therapy was then discontinued in responding patients. The same chemotherapy was reinstituted at the time of relapse. The overall response rate to the induction chemotherapy was 35% and included only one complete response (2%). Median response duration was 9 months. Respondents were off all therapy for a median of 5 months (range, 1-12+ months) and were followed without evidence of progressive disease. Response to retreatment was 30% with no complete responses seen. Overall median survival from the data of diagnosis of metastatic disease was 24 months, with a median survival of 14 months from the date of initiation of therapy. Toxicity for this induction regimen was moderate with two treatment-related deaths secondary to myelosuppression. While the results of this pilot study fail to support the use of non-cross resistant regimens in breast cancer, short-term therapy appears to have no adverse effect on survival and resulted in significant periods during which no therapy was given, resulting in a reduction in overall toxicity. PMID- 3100014 TI - Chemotherapy for carcinomatous peritonitis and pleuritis with MMC-CH, mitomycin C adsorbed on activated carbon particles. Clinical trials. AB - A new drug dosage form comprising activated carbon particles adsorbing mitomycin C (MMC-CH) is designed to slowly release its components, and has affinity for the tumor surface and lymph nodes and a tendency to stay long in the local portion. The therapeutic index of MMC-CH in experimental carcinomatous peritonitis is 3.1 times as high as that of MMC-solution. In clinical experiments 81 patients with carcinomatous effusions were administered with MMC-CH (2.0-2.4 mg/kg in terms of MMC) in bolus intracavitarily. Fifty-one patients responded well to the MMC-CH therapy. Nineteen patients were alive for more than 6 months. The responders showed marked improvement in subjective symptoms, and 26 patients became dischargeable from hospital. Bone marrow suppression and peritoneal irritation were main adverse effects, but the symptoms were temporary and not so serious in spite of a high dose of MMC. PMID- 3100015 TI - Nasally administered buserelin inducing complete remission of lung metastases in male breast cancer. AB - A 60-year-old man with bilateral lung metastases from breast cancer was treated with the gonadotropin-releasing hormone analogue, buserelin, given as an intranasal spray. Androgen deprivation and complete remission of lung metastases were achieved with minimal side effects. Androgen deprivation by means of nasally administered buserelin offers an easy and efficient alternate approach in the treatment of metastatic male breast cancer. PMID- 3100016 TI - Malignant schwannoma in siblings with neurofibromatosis. AB - Three brothers with neurofibromatosis (NF) died of sarcoma. The proband tumor had malignant schwannoma. The histologic nature of the sarcoma in the other two brothers was not known, but it seemed likely to be similar to that of the proband. However, the sarcomatous lesions in these two siblings developed in the patients' right lower limbs which showed clinical and radiological evidence of anterior bowing of the tibia. Their mother and two other siblings have neurofibromatosis, but have not developed malignant tumors. The unaffected father died at age 61 of carcinoma of the common bile duct. An unaffected sister developed adenocarcinoma of both colon and lung. Although it is known that patients with NF are at a high risk of developing malignant sarcoma and second primary malignancies, it is not clear whether this association is genetically determined. The family we report has some of the features of a "cancer family" and suggests that sarcomatous transformation in patients with NF may be genetically influenced. This report raises the possibility that the presence of congenital malformation and exposure to irradiation may predispose patients with neurofibromatosis to develop malignant schwannoma. PMID- 3100017 TI - Neurofibromatosis in a man with a ring 22: in situ hybridization studies. AB - In situ hybridization with a c-sis probe was performed on peripheral lymphocytes of a man with neurofibromatosis and a ring 22 chromosome. Hybridization was observed on both the normal #22 and the ring 22, indicating that the patient is not constitutionally hemizygous for c-sis. The implications of a ring 22 constitution and the neurofibromatosis phenotype are discussed. PMID- 3100018 TI - Differential effects on the metabolism of dimethylnitrosamine and aflatoxin B1 by hepatic microsomes from senescent rats. AB - The ability of hepatic microsomes from senescent rats to metabolize the two potent hepatocarcinogens dimethylnitrosamine (DMN) and aflatoxin B1 (AFB1) was investigated. Seven and 24-month-old male Sprague-Dawley rats were used. Liver weights, and microsomal protein per gram tissue weight were higher, whereas cytochrome P-450 and cytochrome b5 were significantly lower in older rats. Glutathione S-transferases and NADPH cytochrome c reductase activities were dramatically reduced in senescent rats. There was no difference in the formation of formaldehyde from DMN in vitro (31 vs. 34 pmol/nmol P-450) between the young and old rats. In contrast, increased microsome mediated binding of AFB1 to DNA was observed in older rats (116 vs. 228 pmol/nmol P-450) suggesting the possibility of either quantitative or qualitative changes in P-450 species. Additionally the cytoplasmic GSH S-transferases from older rats affected lower inhibition of binding of AFB1 to DNA. These results indicated differential abilities in the hepatic microsomal metabolism of these two carcinogens which may cause differential effects of these carcinogens in senescent rats. PMID- 3100019 TI - Benzo(a)pyrene diol epoxide-I-DNA adduct formation in the epidermis and lung of SENCAR mice following topical application of crude coal tar. AB - The levels of benzo[a]pyrene diol epoxide-I-deoxyguanosine (BPDE-I-dG) adduct formation in epidermis and lung of SENCAR mice following the topical application of benzo[a]pyrene (BP) alone, crude coal tar (CCT) alone, and the two combined were determined in an enzyme linked immunosorbent (ELISA) assay using monoclonal antibodies. Topical application of two doses of BP (20 micrograms) at 72-h intervals, with sacrifice 24 h later resulted in the formation of 197 fmol and 205 fmol BPDE-I-dG adducts per mg DNA in epidermis and lung, respectively. Topical application of 0.5 ml CCT alone resulted in the formation of 278 fmol and 410 fmol BPDE-I-dG adducts per mg DNA in epidermis and lung, respectively. Simultaneous topical application of 20 micrograms BP and CCT (0.1-0.5 ml) resulted in substantially lower BPDE-I-dG adducts in the epidermis as well as in the lung. Our results suggest that CCT may contain inhibitors of carcinogen-DNA adduct formation and that topical application of CCT produces greater effects on DNA-adduct formation in lung than in epidermis. Thus the cancer-causing potency of the polycyclic aromatic hydrocarbons (PAHs) in CCT may be reduced by other anticarcinogenic constituents present in CCT and systemic absorption of carcinogenic PAHs in CCT applied to skin might have tumorigenic effects in other tissues. PMID- 3100020 TI - Sebaceous adenomas with associated epidermal hyperplasia and papilloma formation as a major type of tumor induced in mouse skin by high doses of carcinogens. AB - Application of a single high dose of 7,12-dimethylbenz[a]anthracene (DMBA, 1 mg) or N-nitrosomethylurea (NMU, 0.4 mg) to the ears of either athymic nu/nu or phenotypically normal nu/+ mice (BALB/c background) resulted in the appearance of cutaneous sebaceous adenomas as well as squamous cell tumors, both at the site of application and elsewhere. The incidence of sebaceous adenomas was 10-fold greater than that of squamous cell tumors after DMBA and 4-fold greater after NMU. A high proportion of these sebaceous tumors (69%) exhibited specifically associated hyperplasia of the overlying epidermis. In 57 cases, a squamous cell papilloma had developed from the hyperplastic epidermis. These findings introduce the sebaceous gland as a potentially interesting new model for studies of carcinogen-target cell interaction in mouse skin. PMID- 3100021 TI - Heat-sensitivity and the immune response of a methylcholanthrene-induced tumor. AB - Our results indicate that this methylcholanthrene (MCA)-induced tumor is immunogenic and that its heat-sensitivity is linked to the immune response of the host. Stimulation or reduction of the latter caused a corresponding change in the former. A therapeutic heat-dose failed to protect a majority of the treated mice against a second tumor challenge. PMID- 3100022 TI - Characterization of the indirect antitumor effect of gamma-interferon using ascites-associated macrophages in a human tumor clonogenic assay. AB - The indirect antitumor effects of recombinant gamma-interferon (IFN-gamma) were investigated using an in vitro tumor clonogenic assay modified to include ascites associated macrophages (AAM). Untreated AAM stimulated tumor colony growth; conversely, AAM treated with IFN-gamma at clinically achievable doses demonstrate a significant growth-inhibiting effect. The indirect antiproliferative activity was dependent on the density of AAM. Supernatants from IFN-gamma-pretreated AAM cultures derived from 11 different ovarian cancer patients significantly inhibited the colony growth of ovarian cancer cell line BG-1, as well as five of six other cell lines. Physicochemical characteristics of the supernatant indicated that a significant part of the antiproliferative activity is heat sensitive, destroyed by proteolytic enzymes, and is dependent on RNA and protein synthesis for production. Neutralizing antiserum against tumor necrosis factor significantly reduced the antiproliferative activity of the supernatants. Production of this factor by AAM was induced by exposure to 1000 units/ml of IFN gamma for 15 min, although activity in the supernatants was not detected until 8 h after exposure to IFN-gamma. Potency of the supernatants reached a peak 12 h after priming and ceased by 22 h. Production of antiproliferative activity was maintained over 5 days by intermittent treatment of AAM with IFN-gamma. Combinations of IFN-gamma and supernatant from IFN-gamma-treated AAM showed potentiated antiproliferative activity against BG-1 in an additive to synergistic manner. Antitumor effects of IFN-gamma may be dependent on tumor-associated macrophages and treatment scheduling. PMID- 3100023 TI - Effect of retinoic acid and phorbol-12-myristate-13-acetate on glycosyltransferase activities in normal and transformed cells. AB - Retinoic acid was found to increase the activity of cytidine monophosphosialic acid:lactosylceramide sialyltransferase activity in a nontransformed clonal hamster cell line, NIL 8, and a virally transformed clone, NIL 8-HSV. The potent tumor promoter phorbol-12-myristate-13-acetate (PMA) had no significant effect on sialyltransferase activity in NIL 8 cells but stimulated this activity almost 6 fold when added to NIL 8-HSV cells. There was a synergistically additive effect on sialyltransferase activity when PMA was added to NIL 8 cells in concert with retinoic acid. On the other hand neither PMA nor retinoic acid had an appreciable effect on two other glycosyltransferases measured, uridine diphospho-N acetylgalactosamine:globotriaosylceramide N-acetylgalactosaminyl-transferase and uridine diphosphogalactose:asialoagalactofetuin galactosyltransferase. Examination of sialyltransferase activity in a human epidermoid carcinoma cell line showed a large increase in enzyme activity in response to retinoic acid administration. Two nontransformed hamster cell lines had less basal sialyltransferase activity but also showed marked elevations after retinoic acid treatment. It is proposed that one of the molecular mechanisms underlying the biological effects of retinoic acid and PMA may be an increase in sialyltransferase activity. Possible regulatory mechanisms are discussed. PMID- 3100024 TI - Factors influencing the expression of endogenous retrovirus-related sequences in the liver of B6C3 mice. AB - The expression of RNA transcripts from three families of endogenous retrovirus related sequences was investigated during liver cell proliferation in B6C3 mice. Treatment with a single dose of the liver mitogen and promoter of mouse hepatocarcinogenesis 1, 4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), or with carbon tetrachloride (CCl4), induced liver cell proliferation at days 2 and 3 after treatment. Both of these treatments led to a marked increase in Moloney murine leukemia virus-related 6 kilobase RNAs, which were most abundant at day 1 after TCPOBOP treatment and at day 2 after CCl4. Intracisternal A particle related 6 kilobase RNAs were markedly increased at days 1 and 2 after TCPOBOP and at days 1, 2, and 3 after CCl4. VL30-related transcripts were slightly decreased after TCPOBOP, but they were markedly increased at days 1 and 2 following CCl4. The livers of 15-day-old untreated mice contained about a 3-fold higher level of Moloney murine leukemia virus-related RNAs than adult liver. Intracisternal A particle-related 6-kilobase transcripts were present at 3-fold higher abundance in 7-day-old than in 15-day-old or adult liver. RNAs homologous to VL30 were detected at about the same levels in infant as well as adult livers. Inhibition of protein synthesis by the administration of cycloheximide to adult mice caused a marked increase in the amount of Moloney murine leukemia virus-, intracisternal A particle-, and VL30-related RNAs in the livers of the treated mice, suggesting the existence of labile proteins that normally regulate the abundance of these transcripts. We postulate that the amounts of these putative regulatory proteins vary during both normal development and carcinogenesis and also in response to specific agents that induce liver cell proliferation. PMID- 3100025 TI - Combinations of mesna with cyclophosphamide or adriamycin in the treatment of mice with tumors. AB - Following therapeutic administration, cyclophosphamide and Adriamycin are biotransformed to reactive metabolites, some of which are responsible for undesirable systemic toxicities of these chemicals, whereas others are responsible for their chemotherapeutic effectiveness. Microsomal mixed function oxidases activate cyclophosphamide to produce phosphoramide mustard and acrolein, while cytochrome reductase and xanthine oxidase are capable of transforming Adriamycin and forming free radicals. These reactive metabolites produce unwanted toxic side effects; however, their action may be partially ameliorated by the concomitant administration of thiols. In this study we evaluated the therapeutic activity of combinations of mesna (2-mercaptoethanesulfonate) with cyclophosphamide or Adriamycin in mice with a variety of transplantable tumors (L1210 and P-388 leukemia, Lewis lung and colon 26 carcinoma, B16 melanoma, and M5076 sarcoma). In all cases the administration of mesna prior to cyclophosphamide or Adriamycin treatment did not reduce the antitumor effectiveness of these agents and in some instances (C57BL/6 mice with B16 melanoma or M5076 sarcoma) small improvements were observed. Therefore, the addition of thiols, to reduce effectively the buildup of toxic metabolites of cyclophosphamide or Adriamycin may result in the improved therapeutic effectiveness for these agents in the treatment of cancer. PMID- 3100026 TI - Sensitization of Chinese hamster ovary cells to heat shock by alpha difluoromethylornithine. AB - When exposed to alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, Chinese hamster ovary cells become increasingly sensitive to the cytotoxic effects of elevated temperatures (D.J.M. Fuller and E.W. Gerner, Cancer Res., 42:5046-5049, 1982). This sensitization becomes marked at times greater than 24 h after drug removal, and by 48 h, polyamine-depleted cells that have been exposed to 43 degrees C for 90 min have clonogenic survival values more than two orders of magnitude lower than control populations. Dose response studies demonstrate that, when measured 36 h after removal of the drug, hyperthermic cytotoxicity is maximally potentiated by exposure to DFMO for times as short as 2 to 4 h. A drug concentration of 1 mM for 8 h also elicits maximal response. An additional 8-h drug treatment 24 h after the first fails to further reduce survival in response to heat shock, suggesting the effects of the first exposure are persistent. Intracellular putrescine pools are depleted by the drug within 8 h, and spermidine levels continue to decline for up to 50 h. Consistent with these observations, ornithine decarboxylase (EC 4.1.1.17) activity is found to be reduced for up to 48 h after drug removal. The concomitant depression of spermidine is reflected in the elevation of S-adenosylmethionine decarboxylase (EC 4.1.1.50), which is substrate limited. Putrescine and spermidine show no sign of reaccumulation until approximately 4 days after DFMO exposure. Exposure to exogenous putrescine reversed the sensitization to heat shock induced by DFMO. This effect is quite specific for putrescine (1.4-diaminobutane) and is not replicated by other diamine homologues ranging from 1.3-diaminopropane to 1.8 diaminooctane. Polyamine-depleted cells express thermotolerance with kinetics similar to control cells although overall survival levels are lower. These results suggest that the mechanism of induction and expression of thermotolerance is independent of the role of acid-soluble polyamine pools in cellular responses to heat shock. PMID- 3100027 TI - Preservation of defined phenotypic traits in short-term cultured human breast carcinoma derived epithelial cells. AB - Interpretation of primary monolayer culture of organs and tissues with different epithelial cell types demands well-defined criteria for distinguishing between such cells. Epithelial components in breast carcinomas comprise, in addition to carcinoma epithelial cells (CEP), at least two epithelial cell types organized in mammary ductules of normal appearance as an inner layer of luminal epithelial cells (LEP) and an outer layer of basal or myoepithelial cells (MEP) resting on a basement membrane. In a previous study (Petersen and van Deurs, Cancer Res., 46: 2013-2020, 1986) we have defined a population of CEP in vivo and in vitro, appearing in about 50% of primary carcinomas, by a cytochemical reaction for reduced nicotinamide adenine dinucleotide phosphate neotetrazolium reductase. Carcinoma derived epithelial cells not showing this cytochemical reaction in culture were believed to originate from either carcinoma cells or from mammary ductules of normal or benign appearance. In the present study we show that carcinoma derived NADPH-NT reductase negative cell islets often exhibit phenotypic traits of apparently normal mammary ductules as defined in vivo. Moreover, it is shown that the reductase positive CEP, apart from the reductase reaction, has preserved several other features in culture distinguishing them from cells of apparently normal origin. Thus, whereas reductase positive CEP often consisted of only one cell type, as revealed by phase contrast microscopy, some reductase negative cell islets showed a distinct two-cell-type composition. One cell type exhibited cobblestone-like appearance and remained in the center of the islets whereas the other was more loosely arranged and rapidly left the central area by migration below the cobblestone-like cells to the periphery of the islets. Cobblestone-like cells and loosely arranged cells were found by immunocytochemistry to express elements of LEP and MEP phenotype, respectively. LEP phenotype was defined in vivo by expression of milk fat globule membrane antigen and cytokeratins, whereas MEP expressed basement membrane-associated type IV collagen. Computerized image analysis revealed mean population doubling times for cells with MEP phenotype of 1 day and for those with LEP phenotype of 2 days. Both cell types showed a diploid DNA pattern as revealed by fluorimetry. Reduced nicotinamide adenine dinucleotide phosphate neotetrazolium reductase positive CEP expressed milk fat globule membrane antigen and cytokeratins, thus resembling the reductase negative LEP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3100028 TI - Decarboxylated-S-adenosylmethionine excretion: a biochemical marker of ornithine decarboxylase inhibition by alpha-difluoromethylornithine. AB - In an attempt to define a biochemical marker of ornithine decarboxylase inhibition in humans, alpha-difluoromethylornithine hydrochloride (DFMO), an irreversible ornithine decarboxylase inhibitor, was infused i.v. in seven cancer patients over 10-day courses at doses of 10-90 g/day and 24-h urinary excretion of polyamines and decarboxylated-S-adenosylmethionine was determined before, during, and after treatment. DFMO produces marked increases in urinary decarboxylated-S-adenosylmethionine excretion, up to 84 times pretreatment values. This response appears to be time dependent, requiring several days to reach a maximum and lasting at least 4-5 days after stopping DFMO. In contrast, urinary excretion of the polyamines putrescine, cadaverine, spermidine, N1 monoacetylspermidine, N8-monoacetylspermidine, and spermine, were not consistently altered by DFMO. We conclude that urinary excretion of decarboxylated-S-adenosylmethionine represents a valid biochemical indicator of ornithine decarboxylase inhibition in humans, whereas urinary polyamines are of no value. PMID- 3100029 TI - Extraction of human organ-specific cancer neoantigens from cancer cells and plasma membranes with 1-butanol. AB - Immunoprotective tumor antigens of experimental tumors are selectively extracted by 1-butanol. Human organ-specific cancer neoantigens (OSNs) are tumor substances in cancer extracts to which patients with cancer of the same organ respond in the in vitro assay of leukocyte adherence inhibition. Here we determined whether OSNs as measured by leukocyte adherence inhibition assay are also selectively solubilized by 2.5% (v/v) 1-butanol. Butanol extracts of live tissue-cultured human cancer cells as well as extracts of primary breast cancer contained OSNs as determined by leukocyte reactivity in leukocyte adherence inhibition. With two phase butanol, OSN activity was recovered in the aqueous and not in the organic phase, indicating that OSN is not a lipoprotein. The butanol-soluble OSN, whether allogeneic or autologous, was recognized by the T4 subset of T-cells in association with Class II major histocompatibility complex antigens of monocytes. Autologous OSN was extracted from membrane preparations of autologous primary cancer. Butanol extracts contained the previously identified Mr 40,000 protein OSN. Butanol removed about 50% of the Mr 40,000 protein OSN from live cancer cell membranes. Probably because of residual OSN in the membrane fragments and the ability of OSN to reassociate with the membrane, the T8 subset of pure T-cells responded positively to autologous cancer extracts. Passage of the autologous extract through an anti-Class I major histocompatibility complex antigen affinity column but not through a control affinity column negated the activity of the extract with pure autologous T-cells. The results indicate that human OSNs share with immunoprotective tumor antigens of experimental tumors the unique physicochemical property of being selectively extracted by 2.5% butanol. PMID- 3100030 TI - Disialoganglioside GD2 on human neuroblastoma cells: target antigen for monoclonal antibody-mediated cytolysis and suppression of tumor growth. AB - A murine monoclonal antibody 14.18 specifically recognizes disialoganglioside GD2, the major ganglioside expressed on the surface of human neuroblastoma cells. This monoclonal antibody (Mab) is of immunoglobulin G3 isotype, has an affinity constant (KA) of 3.5 X 10(8) M-1, and reacts preferentially with tumor cells and fresh frozen tumor tissues of neuroectodermal origin in enzyme-linked immunosorbent assay and immunoperoxidase assays, respectively. Mab 14.18 effectively lyses a number of human neuroblastoma cell lines by two distinct mechanisms, i.e., antibody-dependent cellular cytotoxicity and complement dependent cytotoxicity. There is a good correlation between the average number of antibody-binding sites per neuroblastoma cell and the amount of cell lysis observed in complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. In addition, Mab 14.18 suppresses establishment as well as growth of progressively growing, established human neuroblastoma tumors in nude mice when injected 24 h and 9 days, respectively, after the initial s.c. inoculation of tumor cells. These data suggest that Mab 14.18 can mediate tumor cell killing in vivo and in vitro and may thereby prove useful for immunotherapy of human neuroblastoma. PMID- 3100031 TI - Antimetastatic activity of DL-alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, in mice. AB - Our earlier studies indicated a role for polyamines (namely, putrescine, spermidine, and spermine) not only in tumor growth but also in tumor metastases. We have observed that administration of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, resulted in significant inhibition of visually detectable pulmonary metastases in mice implanted with Lewis lung carcinoma. The objective of the present study is to investigate the effect of DFMO on other spontaneous and experimental metastatic models and also to determine which step(s) in the tumor metastatic cascade is sensitive to DFMO. The results presented in this study with malignant mouse B16 amelanotic melanoma (B16a) showed a dose-dependent effect of DFMO on the inhibition of both tumor growth and grossly detectable pulmonary metastases. DFMO, when administered as 0.5, 1, and 2% solution in drinking water, resulted in 0, 24.5, and 60% inhibition of tumor growth, respectively, whereas at the same doses an inhibition of 55, 83, and 96% of visible metastases was observed. At treatment levels of 1 and 2% DFMO, 30 and 65% of the animals were free of metastases. DFMO, at 0.5%, did not show any effect on tumor growth, while a significant 55% inhibition of visible pulmonary metastasis was observed, suggesting a specific role for polyamines in tumor metastasis. DFMO treatment also resulted in a significant reduction of putrescine and spermidine levels with a slight increase in spermine concentration in the tumor tissue. DFMO administration did not inhibit the experimental metastases induced as a result of i.v. injection of B16 melanoma (line F10) tumor and Lewis lung carcinoma cells into the tail vein. These results provide preliminary evidence to indicate that tumor cell polyamine depletion by DFMO might affect the first step in the metastatic cascade, intravasation (i.e., prevent the invasion of metastatic tumor cells into lymphatics or blood vessels), although the effect of DFMO on other steps in the metastatic cascade cannot be ruled out. PMID- 3100032 TI - Prostaglandin and thromboxane synthesis by M5076 ovarian reticulosarcoma during growth: effects of a thromboxane synthetase inhibitor. AB - The five stable metabolites [prostaglandin F2 alpha (PGF2 alpha), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6 ketoprostaglandin F1 alpha (6-keto-PGF1 alpha)] of arachidonic acid (AA) via the cyclooxygenase pathway were measured by high-resolution gas chromatography-mass spectrometry in M5076 ovarian reticulosarcoma (M5) homogenates at various times after tumor implantation (Days 15, 18, 21, and 24). Vegetating tumor showed an active AA overall metabolism, which significantly increased during tumor growth. Synthesis of selected products (TXB2, PGD2, and PGE2) increased markedly over time (up to 10.6, 3.5, and 0.9 micrograms/g, respectively). The overall metabolic profile was TXB2 much greater than PGD2 greater than PGF2 alpha greater than 6 keto-PGF1 alpha greater than PGE2 on Day 15 and TXB2 much greater than PGD2 much greater than PGF2 alpha greater than 6-keto-PGF1 alpha on Day 24. TXB2 was also by far the most abundant product of in vitro-cultured M5 cells. Chronic treatment of M5-bearing mice with dazmegrel (UK-38,485), a selective thromboxane synthetase inhibitor (100 mg/kg p.o. daily, from Day 7 to killing), resulted in incomplete TXB2 synthesis inhibition, AA metabolism diversion toward the other prostaglandins, and no effects of tumor growth and metastasis. More frequent dazmegrel treatment (100 mg/kg p.o. every 8 h from Day 1 to killing) resulted in complete TXB2 synthetase inhibition, AA metabolism diversion, and increased tumor growth and metastasis. These data do not support the hypothesis of thromboxane synthetase inhibitors reducing tumor growth. However, since TXB2 suppression was accompanied by the production of other products possibly interfering in tumor growth, no conclusions on the effective role of TXA2 in malignancy can be drawn. PMID- 3100033 TI - Paying for patient care in treatment research--who is responsible? PMID- 3100034 TI - Phase II trial of ifosfamide in children with malignant solid tumors. AB - Ifosfamide was given to 61 patients with malignant solid tumors diagnosed before the age of 21 years. In this phase II study, all patients received 1.6 g/m2/day X 5 iv over 15 minutes followed by mesna at a dose of 400 mg/m2 iv at 15 minutes and 4 and 6 hours after ifosfamide. Responses were observed in five of 15 patients with osteosarcoma, two of ten with neuroblastoma, two of six with Wilms' tumor, two of five with rhabdomyosarcoma, four of eight with other soft tissue sarcomas, one of one with retinoblastoma, one of two with germ cell tumors, one of one with B-cell lymphoma, and one of one with a primitive neuroectodermal tumor. Fifty-nine of 61 patients had received prior alkylating agent therapy which included cyclophosphamide, cisplatin, mechlorethamine, melphalan, or dacarbazine. Fourteen of 19 responses developed in patients whose tumors were resistant to treatment with cyclophosphamide. A patient with malignant Schwannoma who had received no prior chemotherapy developed a complete response which lasted 12 months. A patient with brain metastases of osteosarcoma has had complete response for greater than 2 years. Complete response was also observed in a patient with B-cell lymphoma. Toxicity consisted of mild to moderate nausea and vomiting, transient reversible myelosuppression, occasional elevation of serum BUN or creatinine, and transient neurotoxicity characterized by somnolence, confusion, weakness, tremor, hallucinations, or seizures. We conclude that ifosfamide is an important alkylating agent without apparent complete cross resistance with cyclophosphamide, and as such should be further investigated for determination of its activity in patients with pediatric neoplasms and considered for incorporation into phase II-III trials for certain tumors. PMID- 3100035 TI - Survey of the effect of adding Fluosol-DA 20%/O2 to treatment with various chemotherapeutic agents. AB - The tumor growth delays (TGDs) observed with a series of antineoplastic agents with or without Fluosol-DA and carbogen breathing (95% oxygen, 5% carbon dioxide) in the FSaIIC fibrosarcoma are shown. All but two of eleven alkylating agents examined showed some degree of positive effect by the addition of Fluosol-DA and carbogen breathing to drug treatment. The largest effects were seen with busulfan and procarbazine. Melphalan and the nitrosoureas, carmustine, lomustine, semustine, and chlorozotocin, gave increases in TGD ranging from 2- to 6-fold with the addition of Fluosol-DA and carbogen breathing. Modest increases were seen with cytoxan and dacarbazine. Cisplatin showed no additional TGD with Fluosol-DA and carbogen breathing, and mitomycin showed a negative effect. The addition of Fluosol-DA and carbogen breathing to bleomycin treatment increased the TGD produced by 5- to 6-fold compared to the drug alone. With vincristine and etoposide at three different doses, TGDs increased 2.4- to 3-fold in combination with Fluosol-DA and carbogen breathing. Increases of 1.3- to 1.4-fold in the TGD were observed with methotrexate and 5-fluorouracil with Fluosol-DA and carbogen breathing. Adding Fluosol-DA and carbogen breathing to treatment with several of the drugs examined resulted in significant enhancement of TGD and therefore may lead to an improved therapeutic outcome when added to certain currently used clinical regimens. PMID- 3100036 TI - Gonadal and sexual function in male patients with hairy cell leukemia: lack of adverse effects of recombinant alpha 2-interferon treatment. AB - Gonadal and sexual function was evaluated in 81 male patients with hairy cell leukemia (HCL). Forty-eight patients were receiving recombinant alpha 2b interferon (INF) therapy, and 33 patients were receiving no systemic therapy at the time of evaluation. Among 28 patients with stable HCL who were receiving no systemic therapy, elevated serum follicle-stimulating hormone (FSH) was observed in two patients, while serum luteinizing hormone (LH) was normal in all. Serum testosterone levels were below normal in seven of 28 patients on no systemic therapy. Hormone levels were followed prospectively for a median of 8 months in 11 patients receiving INF without prior chlorambucil therapy. FSH became elevated in only one of eight patients with normal pretreatment values, LH remained normal in all patients, and testosterone transiently fell in two of four patients with normal pretreatment values. In addition, 20 of 29 patients receiving INF who had normal FSH and LH levels when first examined continued to have normal levels during a median of 10 months of INF therapy. Patients receiving INF generally reported either no change or improvement in sexual function as therapy progressed. We conclude that most patients with stable HCL have normal testicular function and that INF therapy does not appear to produce significant gonadal toxicity. PMID- 3100037 TI - Phase II study of recombinant gamma-interferon in patients with advanced nonosseous sarcomas. PMID- 3100039 TI - Methodology and results of intravenous thrombolysis in acute myocardial infarction. AB - For the vast majority of patients with acute myocardial infarction, intravenous thrombolysis is at present the only therapeutic approach aimed at early reperfusion of the ischemic myocardium. Rapid recanalization of the infarct related coronary artery is achieved in at least 50-60% of the patients by short term high-dose infusions of streptokinase or urokinase with a low risk of bleeding. A substantial reduction of infarct size, however, can be expected in only a minority of patients, mostly in those who are treated very early. The effects of intravenous thrombolysis on early and late mortality from acute myocardial infarction are still equivocal; more conclusive data may be expected from ongoing randomized trials. PMID- 3100040 TI - Angiographic and radiologic comments on thrombolytic therapy in acute myocardial infarction. PMID- 3100038 TI - Streptokinase, urokinase, and tissue plasminogen activator: pharmacokinetics, relative advantages, and methods for maximizing rates and consistency of lysis. AB - Early reperfusion of occluded coronary arteries offers great promise as a method for minimizing myocardial damage after acute myocardial infarction. Such reperfusion is usually attempted via administration of fibrinolytic agents. Urokinase may hold marginal advantages over streptokinase, especially in patients with high preexisting titers of antistreptokinase antibodies. These minor differences, however, pale in comparison to important advantages demonstrated by the newly developed agent, tissue plasminogen activator (t-PA). The advantages of t-PA derive primarily from its property of binding to, and being activated by, fibrin. Consequently the generated plasmin is also fibrin-bound, the bound plasmin is protected from circulating antiplasmin and therefore more efficiently utilized, and circulating fibrinogen is spared. Preliminary clinical experience indicates that the frequency of favorable response after intravenous administration of t-PA is considerably greater than after SK. A major determinant of clinical benefit after reperfusion is the brevity of ischemia. Selective intracoronary infusion of fibrinolytic agent produces faster lysis than does intravenous infusion, and rate of lysis may be further accelerated by transcatheter disruption of clot and intrathrombic injections of highly concentrated urokinase or t-PA. Even maximally accelerated lysis, however, cannot fully compensate for the inherent delay imposed by catheterization. For that reason, prompt intravenous infusion of fibrinolytic agents, presumably t-PA, seems preferable to the intracoronary route. In the effort to initiate fibrinolytic therapy at the earliest feasible time after infarction, administration by paramedics, or even home administration after training, is a program worthy of exploration. PMID- 3100041 TI - Early diagnosis and medical treatment of the persistent ductus arteriosus in infants. AB - Diagnosis of an isolated patent ductus arteriosus (PDA) is usually straightforward. If at later age it is associated with pulmonary hypertension, however, the symptoms may be variable and more difficult to assess. In the age group primarily discussed here, pulmonary hypertension is frequently present, so diagnosis cannot be based on physical findings alone. Echocardiography and Doppler echocardiography are essential diagnostic procedures; however, cardiac catheterization and angiography may still be needed especially in cases with associated heart defects. At present, surgical closure of the PDA is the therapy of choice in infants. In preterm newborns, an attempt by medical treatment is indicated and often promising. Unfortunately, there are no interventional techniques available at present for duct closure in this age group, whereas in some centers catheter closure of a PDA is successfully employed in older children. PMID- 3100043 TI - An orderly approach: comments on the intravascular use of lasers. PMID- 3100042 TI - Transluminal closure of patent ductus arteriosus: long-term results of 208 cases treated without thoracotomy. AB - Patent ductus arteriosus was the first inborn cardiac defect ever eliminated by percutaneous transvascular therapy. The method, results, and complications of Ivalon plugging of the ductus in 208 patients between 5 and 62 years old and treated between 1967 and 1985 are described. Permanent closure was accomplished in 197 patients (94.7%). The following particular benefits are obtainable from the method: no need for thoracotomy; local anesthesia applicable to 65% of all cases; 30 mm average time of intervention; only moderate invasiveness to the patients; only 7 days of hospitalization; good cost-benefit ratio. PMID- 3100044 TI - Dopamine- and octopamine-sensitive adenylate cyclase in the brain of adult Culex pipiens mosquitoes. AB - The effects of dopamine and octopamine on adenylate cyclase activity were studied on the head homogenate of adult Culex pipiens mosquitoes in vitro. Both dopamine and octopamine were shown to increase the cyclic AMP content in the homogenate. The antagonist haloperidol blocked the production of cyclic AMP induced from dopamine but had no effect on the production of cyclic AMP induced by octopamine at the concentrations tested. The opiate agonist etorphine was ineffective at reducing cyclic AMP levels induced by either dopamine or octopamine at the concentrations tested. PMID- 3100045 TI - [Folliculogenesis and ovulation induction]. PMID- 3100046 TI - [Intravenous supplementation of amino acids]. PMID- 3100047 TI - [Use of the BMS-3 Radiometer blood gas analyzer for indirect calorimetry]. PMID- 3100048 TI - Diversity achieved by diverse mechanisms: gene conversion in developing B cells of the chicken. PMID- 3100049 TI - Somatic diversification of the chicken immunoglobulin light chain gene is limited to the rearranged variable gene segment. AB - Previous studies have shown that the chicken lambda immunoglobulin light chain gene undergoes a single rearrangement that results in functional VJ joining of the unique variable (V lambda 1) and joining (J lambda) coding regions. The immunologic repertoire of lambda genes is created through extensive sequence diversification within the rearranged locus during B cell development in the bursa of Fabricius. This sequence diversification was detected only at the rearranged V lambda 1 segment and not within the 5' leader sequence, the J lambda segment, or the unrearranged V lambda 1 segment. The selective diversification of the rearranged V lambda 1 segment was associated with unique DNAase I hypersensitive sites on the rearranged allele. While probes for V lambda 1 sequences detect multiple homologous V lambda segments, probes for both the 5' leader and J lambda segments fail to detect homologous sequences. Taken together, these results suggest that a highly selective process, possibly gene conversion, operates during B cell ontogeny to generate diversity within the lambda gene. PMID- 3100050 TI - A hyperconversion mechanism generates the chicken light chain preimmune repertoire. AB - The chicken immunoglobulin light chain repertoire has been shown to be entirely derived from a single V lambda 1-J rearranged combination. The complete coding information of the lambda locus was determined: it comprises 25 V-hybridizing elements, all of which are pseudogenes, clustered in both orientations within 19 kb of DNA, starting 2.4 kb upstream of the V lambda 1 gene. Sequences of somatically rearranged V lambda 1 genes from embryonic and posthatching bursal cells show that diversification of light chain sequences occurs during ontogeny by a segmental gene conversion mechanism which takes place at a frequency of 0.05 0.1 per cell generation between the pseudogene pool and the unique rearranged functional V gene. PMID- 3100051 TI - A molecular analysis of transformer, a gene in Drosophila melanogaster that controls female sexual differentiation. AB - The transformer (tra) gene regulates all aspects of somatic sexual differentiation in Drosophila melanogaster females and has no function in males. We have isolated the tra gene as part of a 200 kb chromosomal walk. The 25 kb region around tra contains four genetically identified complementation groups and at least six transcriptional units. Germ-line transformation experiments indicate that a fragment of 2 kb is sufficient to supply tra+ function. Mapping of cDNAs from tra and from the adjacent genes indicates that the tra+ transcription unit is 1.2 kb or less. This transcription unit gives rise to a 1.0 kb RNA that is female-specific and a 1.2 kb RNA that is present in both sexes. tra+ and the gene at the 3' side overlap slightly in the 3' ends of their RNA coding sequences. These results suggest that tra+ function is regulated at the level of production of the female-specific tra RNA. The fact that a tra transcript is found in males raises interesting possibilities for how tra expression is controlled. PMID- 3100052 TI - The Saccharomyces and Drosophila heat shock transcription factors are identical in size and DNA binding properties. AB - The heat shock transcription factor (HSTF) has been purified to apparent homogeneity from S. cerevisiae and D. melanogaster by sequence-specific DNA affinity chromatography. A synthetic oligonucleotide containing an hsp83-like heat shock element (HSE) was prepared and ligated into concatamers and covalently coupled to Sepharose. This DNA-affinity resin allowed the rapid isolation of a yeast and a Drosophila protein with the same apparent molecular weight (70 kd). The yeast HSTF will bind to both its own and the Drosophila HSEs. Similarly, the Drosophila HSTF will bind to both its own and the yeast HSEs. The yeast and Drosophila HSTFs were subjected to preparative SDS gel electrophoresis, and the 70 kd polypeptides were eluted, renatured, and observed to generate the identical footprint pattern as the native HSTFs. Affinity-purified Drosophila HSTF was further shown to stimulate specific HSE-dependent transcription from a Drosophila hsp70 gene in vitro. PMID- 3100053 TI - A novel mechanism of immunosuppression mediated by ethanol. AB - Ethanol in concentrations equivalent to levels achieved by the ingestion of moderate amounts of alcoholic beverages has been shown to inhibit human T lymphocyte proliferation after activation in vitro by mitogens, phorbol myristic acetate, or anti-CD3 monoclonal antibodies. As determined by probit analysis, this inhibition was monophasic, suggesting that ethanol affected a single limiting component of T-cell proliferation. In experiments designed to test the effect of ethanol on various aspects of proliferation, it was demonstrated that ethanol did not inhibit interleukin 2 (IL-2) production or the acquisition of IL 2 receptors. However, the capacity of exogenously supplied IL-2 to stimulate proliferation of T cells that had previously acquired IL-2 receptors was suppressed by ethanol in a dose-dependent manner, and this suppression was monophasic. Consequently, ethanol was able to inhibit T-lymphocyte proliferation when added several days after the initial stimulation. This mechanism appears to be unique among immunosuppressive agents thus far studied; cyclosporin A and corticosteroids inhibit IL-2 production and are required at the initiation of activation for maximal effect. Synergistic inhibition of T-cell proliferation was seen with ethanol plus cyclosporin A: the level of inhibition with 250 ng/ml cyclosporin A alone was equivalent to the level seen with 62 ng/ml cyclosporin A plus 5 mM (24 mg%) ethanol. PMID- 3100054 TI - Evaluation of ricin A-chain immunotoxins directed against human T cells. AB - We have synthesized four immunotoxins (ITs) by covalently coupling the A chain of ricin to murine monoclonal antibodies that recognize surface antigens on human T cells. Treatment of human peripheral blood lymphocytes with either 10.2-A, directed against the CD5 (Tp67) antigen, or 64.1-A, directed against the CD3 (Tp19) antigen, abolished protein synthesis in cells subsequently cultured with phytohemagglutinin (PHA). In contrast, two other ITs (9.6-A and 35.1-A), both directed against the CD2 (Tp50) antigen, had minimal effects on protein synthesis in PHA-stimulated cells. The binding of each IT to T cells was shown by immunofluorescence with fluorescein-conjugated goat anti-mouse immunoglobulin (FITC-GAMIg) and fluorescein-conjugated rabbit anti-ricin A-chain (FITC-RAR) antibodies. Activity of the ricin A chain in each IT was demonstrated by its ability to inhibit protein synthesis in a cell-free reticulocyte lysate assay. Ultrastructural immunoperoxidase analysis of IT internalization showed that ineffective and effective ITs were endocytosed at the same rate (50% of cells had labeled endosomes after 15 min). However, ineffective IT 35.1-A was more rapidly delivered to lysosomes (15-30 min) than effective ITs (10.2-A and 64.1-A) (greater than or equal to 30 min). The data support the hypothesis that there are several distinct pathways for internalization of ITs and that the ability of ricin A chain to reach and inactivate ribosomes may depend upon the specific membrane receptor involved in binding a given IT, its route of internalization, and the rate of entry of the IT into lysosomes. PMID- 3100055 TI - The regulation of gamma-interferon production by interleukins 1 and 2. AB - Purified interleukins 1 and 2 (IL-1 and IL-2) were used to investigate their role in the production of gamma-interferon (gamma-IFN). Macrophage depletion from human peripheral blood mononuclear leukocytes (PBML) inhibited gamma-IFN production. Addition of purified IL-1 partially restored IFN production of macrophage-depleted PBML induced by three T cell mitogens (phytohemagglutinin, PHA; concanavalin A, con A; and staphylococcal enterotoxin A, SEA), but had no effect on induction of IFN production by undepleted PBML. Therefore endogenous IL 1 production by macrophages is probably one of the mechanisms by which they act as accessory cells for IFN production by lymphocytes. A monoclonal antibody 9.6 which binds to the sheep erythrocyte (E) receptor found on human T cells inhibited IFN production. Addition of IL-2, but not IL-1, was found to reverse this inhibition. Prostaglandin E2, a macrophage product, inhibited gamma-IFN production induced by PHA, Con A, and OKT3 but usually not SEA. This inhibitory effect was reversible by the addition of IL-2 but not IL-1. In the absence of mitogen IL-1 alone rarely induced any IFN production, although some IFN was produced by PBML from a small minority of donors. Without mitogen IL-2 induced IFN production only at very high concentrations and the added presence of IL-1 did not enhance this induction. PMID- 3100056 TI - Mouse monoclonal antibodies against bromelain-treated mouse erythrocytes: reactivity with erythrocytes of various species of animals and idiotypes. AB - Spleen and peritoneal cells from unimmunized BALB/c mice were cultured in the presence of LPS for 24 hr and fused to produce hybridomas secreting antibodies against bromelain-treated mouse erythrocytes (BrMRBC). Three clones from spleen cells and eight clones from peritoneal cells were isolated and characterized further. All the monoclonal antibodies had IgMK isotype. Their reactivities against untreated and bromelain-treated erythrocytes from various species were assessed by hemolysis and indirect radioimmunoassay; all the clones had similar antigen specificities. On the isoelectric focussing patterns of light chains, they were separated into two groups, two and nine clones, and all the light chains in each group showed identical patterns. The two groups shared no common idiotope detectable by anti-idiotype antibodies prepared by immunization of rabbits with the monoclonal antibodies, but all the antibodies in each group shared common idiotopes. In each group, one antibody had a unique idiotope different from any other antibody, but eight antibodies in a group shared another identical idiotope. These findings suggest the restricted heterogeneity of anti BrMRBC antibodies in the mouse. PMID- 3100057 TI - Proliferation of human peripheral blood lymphocytes induced by recombinant human interleukin 2: contribution of large granular lymphocytes and T lymphocytes. AB - Recombinant human interleukin 2 (rH IL-2) in the presence or absence of additional stimuli, was found to be able to induce and support the proliferation of human peripheral blood lymphocytes (PBLs). These proliferative effects were observed at low doses (less than or equal to 10 U/ml) of interleukin 2 (IL-2) only when additional signals (antigen, mitogen) were provided. However, higher doses (greater than or equal to 100 U/ml) of rH IL-2 significantly stimulated the proliferation of PBL even in the absence of exogenous lectin, antigen, or allogeneic serum. The subpopulation of lymphocytes most responsive to these higher doses of rH IL-2 was the large granular lymphocyte (LGL), the morphologic homologue of natural killer activity. After the separation of human PBLs on discontinuous Percoll gradients, cells from fraction 2 (greater than 90% LGLs) responded in a dose-dependent manner to rH IL-2 alone, whereas cells from fraction 6 (greater than 90% T cells) were only slightly responsive to rH IL-2 alone. A portion of the proliferation of cells from fraction 2 was dependent on the expression of the TAC receptor, because the prior removal of TAC-positive cells significantly reduced IL-2-induced lymphocyte proliferation. These results demonstrate that human LGL that have not been exogenously stimulated can proliferate in direct response to IL-2, and suggest that LGL are the major cellular phenotype in the proliferative response that has been observed clinically. PMID- 3100058 TI - LPS-stimulated release of prostaglandin E and thromboxane B2 from the U937 cell line. AB - Human monocytes are known to metabolize arachidonic acid (AA) and to release prostaglandins upon stimulation. Previous data indicate that in vitro maturation and differentiation of monocytes result in alteration of this property with greatly diminished response to stimulators of release of prostaglandin E (PGE) and thromboxane B2 (TxB2) occurring after cells have been cultured. To further study the effects of differentiation on human monocyte AA metabolism, a model system was established based upon the human histiocytic cell line U937. Among tested stimulants, which included opsonized zymosan, complement fragment C3b, phorbol myristate acetate (PMA), calcium ionophore A23187, and concanavalin A, it was found that Escherichia coli lipopolysaccharide (LPS) was unique in that it stimulated increased release of TxB2 from U937 cells. The effect of the phorbol ester PMA, a compound commonly used to induce differentiation of U937, on the ability of U937 to respond to LPS was examined. Following 48 hr of treatment with PMA, U937 became capable of releasing both PGE and TxB2 in response to small doses of LPS. As previously observed for human monocytes, the release of PGE was delayed for several hours following stimulation and failed to reach maximal cumulative levels in culture until 24-48 hr following stimulation. In contrast to human monocytes, PMA-induced U937 were capable of maintaining their responsiveness to LPS for several days. Thus, the U937 cell line provides a useful model for study of the effects of differentiation of human mononuclear phagocytes on their ability to metabolize AA, and for the effects of LPS on histiocytic tumor cell prostaglandin release. PMID- 3100059 TI - Interleukin 2 induces interferon alpha/beta production in mouse bone marrow cells. AB - We have previously reported that mouse bone marrow (BM) cells stimulated with alloantigen produce cytotoxic effector T-cell activity and produce interferon (IFN-)alpha/beta. In this report we show evidence suggesting that interleukin 2 (IL-2) may play a role in this IFN-alpha/beta production by alloantigen stimulated BM cells. Alloantigen-induced IFN production by bone marrow cells was completely inhibited when cultures were supplemented with antisera to IL-2. Cell free supernatants obtained at 2 days from cultures containing C57BL/6 BM cells and irradiated DBA/2J spleen cells were also shown to contain low levels of IL-2 activity and induced significant IFN production in fresh BM cells. Different IL-2 preparations were tested for their ability to induce IFN-alpha/beta production in mouse BM cells. Mouse BM cells cultured with recombinant human IL-2 or highly purified mouse IL-2 produced high levels of IFN-alpha/beta activity after 2-3 days of culture with significant IFN activity being detected as early as 24 hr of culture. IL-2-induced IFN-alpha/beta production was partially resistant to irradiation. In contrast, irradiated (2000 rad) bone marrow cells failed to produce any IFN when cultured with alloantigen in the absence of IL-2. T-cell depleted BM cells or BM cells obtained from C57BL/10 nude mice produced high levels of IFN-alpha/beta following stimulation with IL-2. In addition, bone marrow cells depleted of Ia+, Qa 5+, or Asialo GM+1 cells produced IFN in response to IL-2. Thus, neither T cells nor NK cells are required for IL-2 induced IFN-alpha/beta production by BM cells. The action of IL-2 on bone marrow cells to induce IFN production was mediated by the classical IL-2 receptor, since monoclonal antibodies to the IL-2 receptor present on T cells blocked this response and since bone marrow cells depleted of IL-2 receptor-bearing cells failed to produce IFN when cultured with IL-2. These results suggest that non-T cells resident in the BM have receptors for IL-2 and can produce IFN-alpha/beta upon stimulation by IL-2. Since IFN has been shown to affect different aspects of hematopoiesis, the production of IFN by BM cells stimulated by IL-2 may be important in the control of hematopoiesis. In addition, IL-2-induced IFN production may play a role in graft-versus-host disease. PMID- 3100060 TI - Interleukin 1 and protein kinase C activator are dissimilar in their effects on Il-2 receptor expression and Il-2 secretion by T lymphocytes. AB - T lymphocytes respond to mitogenic stimulation by expressing the receptor for interleukin 2 (Il-2) and secreting Il-2; once the receptor is expressed, Il-2 induces these cells to proliferation. In the present report using mouse T lymphocytes, thymocytes, and the lymphoma cell line EL4, we studied receptor expression and Il-2 secretion as early parameters for T-lymphocyte activation in response to ionomycin, concanavalin A (Con A), 12-O-tetradecanoyl-phorbol 13 acetate (TPA), and interleukin 1 (Il-1). Il-1 is required for mitogenic response of lymphocyte preparations that are rigorously depleted of macrophages. On its own, Il-1 had very little effect on Il-2 secretion and Il-2 receptor expression by T lymphocytes. TPA strongly synergized with ionomycin both for Il-2 secretion and for Il-2 receptor expression whereas Il-1 did not. Il-1 required the simultaneous presence of ionomycin and TPA to have any demonstrable effect on T lymphocytes from spleen and on thymocytes. However, on EL4 cells which were also partially responsive to TPA alone, Il-1 showed strong synergy with TPA to induce Il-2 secretion and Il-2 receptor expression. The effect of Il-1 on EL4 cells was dose dependent where increasingly higher concentrations of Il-1 in the presence of a fixed concentration of TPA caused higher percentage of EL4 cells to become Il-2 receptor positive. The present results suggest that Il-1 does not cause its effect on T lymphocytes via the same mechanism of protein kinase C activation that has been proposed for TPA. PMID- 3100061 TI - Heterogeneity of B-cell growth factor receptor reactivity in healthy donors and in patients with chronic lymphatic leukemia: relationship to B-cell-derived lymphokines. AB - Twenty-five long-term B-cell lines were studied for B-BCGF activity. The cell lines were cultured in the presence or absence of the new tumor promoter teleocidin, and control and teleocidin-treated derived supernatants were cocultured with purified B cells obtained from healthy donors and patients with B chronic lymphatic leukemia (B-CLL), in the presence of anti-mu. In attempt to delineate the role of other B-cell lymphokines in promoting proliferation of activated B cells, the supernatants were also studied for interleukin 1 (IL-1), interleukin 2 (IL-2), and interferon gamma (IFN-gamma). The effect of B-cell derived lymphokines on the proliferation of activated B cells obtained from the 14 donors was heterogeneous, and three types of response were observed: In four healthy donors there was induction of B-cell proliferation by B-cell lymphokines derived from both control cells and teleocidin-treated cells. In cells obtained from the other five healthy donors there was induction of B-cell proliferation by B-cell lymphokines derived from teleocidin-treated cells. In the five B-CLL patients, B-cell proliferative response to B-cell lymphokines derived from both control cells and teleocidin-activated cells was absent. Comparison of B-BCGF reactivity to T-BCGF reactivity demonstrated that B-CLL B lymphocytes did not respond to either B-BCGF or T-BCGF, whereas normal B cells responded to T-BCGF and may proliferate upon stimulation with B-cell-derived IL-2 and/or B-BCGF. These results suggest heterogeneity of B-BCGF receptor reactivity in B lymphocytes derived from healthy donors, and lack of both B-BCGF and T-BCGF receptor reactivities in B lymphocytes derived from B-CLL patients; B-cell derived lymphokines influence normal B-cell response but not leukemic B cells; B BCGF optimal effect is in large part due to other B-cell lymphokines, especially B-cell-derived IL-2; the possible existence of various B-BCGFs. PMID- 3100063 TI - Is there an interleukin 2 inhibitor in human serum? AB - Normal mouse serum has been shown to contain an inhibitor of interleukin 2 (IL 2). Here we report that a molecule with similar activity cannot be found in normal human serum (NHS). Although NHS inhibited the IL-2-dependent proliferation of mouse CTLL cells, as expected of an IL-2 inhibitor, it also had inhibitory activity on IL-3-dependent cells and was cytolytic to IL-2-independent mouse cells as measured by a 51Cr release assay, indicating a nonspecific effect. In addition, NHS had no effect on the IL-2-dependent proliferation of human peripheral blood T-cell blasts. Fractionation of NHS by size exclusion HPLC failed to separate cytolytic activity from any putative true IL-2 inhibitor activity. The cytolytic component was not related to immunoglobulin since it had a molecular weight of 50,000 to 60,000 and was not bound by protein-A-Sepharose. However, its molecular weight, heat lability, and trypsin sensitivity suggest it to be a protein. PMID- 3100062 TI - Inhibitors of IL-2 production and IL-2 receptor expression in human leukemic T cell line, Jurkat. AB - 1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a protein kinase inhibitor, suppressed interleukin 2 (IL-2) production and IL-2 receptor (IL-2R) expression of the human leukemic T-cell line, Jurkat, induced by 12-O-tetradecanoyl-phorbol 13-acetate and phytohemagglutinin-P. This effect was significant at 5 microM H-7 without loss of cell viability. Such activity was not observed with N-(2 guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004), a potent inhibitor of cGMP- and cAMP-dependent kinases, and a weak inhibitor of Ca2+-phospholipid-dependent protein kinase (protein kinase C). These findings suggest that protein kinase C is more closely associated with IL-2 receptor expression and IL-2 production of T cells than cGMP- or cAMP-dependent kinases. In addition, N-(6-aminohexyl)-5 chloro-1-naphthalenesulfonamide (W-7), a calmodulin inhibitor, suppressed both IL 2 production and IL-2R expression. Cycrosporin A (Cy A), a potent immunosuppressive drug, markedly inhibited IL-2 production of Jurkat cells whereas it did not affect the IL-2R expression. Thus, the mechanism of action of Cy A appears to differ from that of the protein kinase inhibitor, H-7, and the calmodulin inhibitor, W-7. PMID- 3100064 TI - Murine thyroid follicular epithelial cells can be induced to express class II (Ia) gene products but fail to present antigen in vitro. AB - To determine whether thyroid follicular epithelial cells (TFEC) might be involved in the induction of autoimmune thyroiditis, they were tested for their potential to express Ia antigens, and for their ability to present antigen in vitro. Results showed that Ia antigens, absent on normal TFEC, could be readily induced with interferon gamma, as detected by immunofluorescence. Maximal expression of Ia antigens in over 50% of TFEC was observed after 4 days of culture in the presence of IFN-gamma, and was quantitatively comparable to spleen cells by cytofluorometric analysis. Moreover, primary TFEC in culture secreted thyroglobulin (tg) and interleukin 1. However, TFEC consistently failed to stimulate various populations of T cells. These included lymph node cells sensitized to tg, a T-cell clone specific for azo-benzene-arsonate tyrosine (ABA), and a hybridoma specific for beef insulin. Likewise, Ia-positive TFEC did not stimulate T-cell hybridomas restricted to the class II alloantigen I-Ab, while stimulating a hybridoma specific for the class I alloantigen Kb. T-cell unresponsiveness could not be explained by inhibitory activity of TFEC, released either into the culture supernatant or exerted by cell contact. The data indicate that Ia-positive TFEC failed to serve as class II-restricted antigen-presenting cells (APC) in vitro and thus argue against a primary role for these cells in the inductive phase of thyroiditis. PMID- 3100066 TI - Studies of the mechanism by which gangliosides inhibit the proliferative response of murine splenocytes to concanavalin A. AB - Gangliosides are known to inhibit the proliferative response of murine and human lymphocytes to antigens and mitogens in vitro. In this study the response of murine spleen cells to concanavalin A (Con A) was used as a model system. Analysis of the cellular events by flow cytometry revealed that during the first 24 hr of culture the effect of gangliosides on Con A-treated cells was minimal. At 48 hr, however, more of the ganglioside-treated cells were in G0/G1, the cells contained more RNA, and fewer cells were in S phase. These data indicate that gangliosides inhibit the transition of the cells from G0/G1 into the S phase of the cell cycle. Expression of the interleukin 2 (IL-2) receptor, as measured by the binding of a monoclonal antibody to the receptor, was not inhibited by the gangliosides. Binding of 125I-labeled recombinant IL-2 to cells cultured for 48 hr with Con A was inhibited by ganglioside GD1a but not by asialo GM1. Inhibition was much more effective if the gangliosides were preincubated with IL-2 before addition of cells, but no inhibition was observed if the cells were preincubated with gangliosides and the unbound gangliosides were washed out prior to addition of the IL-2. These data suggest that interference with the binding of IL-2 to the high-affinity IL-2 receptor of activated T lymphocytes plays an important role in the inhibition of Con A-induced proliferation. PMID- 3100065 TI - Ir gene-controlled response to haptenated hen ovomucoid: isotypic specificity and dominant nonresponsiveness. AB - We have examined the isotypic pattern of the response of mice to the Ir gene controlled antigen, dinitrophenyl-ovomucoid (DNP-OM). H-2 kappa mice are high responders (HR); (H-2b,d mice are low responders (LR). The isotype patterns of HR and LR strains differ both quantitatively and qualitatively. In the primary response to doses of 20-100 micrograms DNP-OM, HR strains produce IgM and IgG antibodies, whereas LR strains produce only IgM. Background genes modify the kinetics of the IgGl primary response in HR strains, but no background was found which allowed an IgG response in a LR strain. In secondary responses, priming with 0.2 microgram DNP-OM increases secondary responses in HR strains, and decreases them in LR strains. Control of this response maps to I-A, and is not altered by the bm 12 I-Ab mutation. The LR phenotype is dominant in (HR X LR)F1 mice. PMID- 3100067 TI - [Immunologic reactivity and arachidonic acid metabolism in patients with multiple sclerosis. Study of mononuclear leukocyte adherence inhibition]. PMID- 3100068 TI - [Changes in the voice in type II mucopolysaccharidosis]. PMID- 3100069 TI - Medicare reimbursement for CRNAs becomes reality. PMID- 3100070 TI - In vitro effects of Bacillus subtilis on the immune response. AB - The authors evaluated the in vitro effects of Bacillus subtilis on the following parameters of the immune response: mitogenic T cell proliferation (by PHA and OKT3) and mitogenic-induced lymphokine production (IL-2 and IFN-gamma). The spores of Bacillus subtilis did not influence the immune response, while its vegetative forms enhanced mitogenic-induced T cell proliferation. Both spores and vegetative forms did not modify lymphokine production. PMID- 3100071 TI - Effects of an adjunctive treatment with Bacillus subtilis for food allergy. AB - The authors evaluated the clinical efficacy of an adjunctive treatment with spores of Bacillus subtilis in 20 adult patients with urticaria-angioedema syndrome from food allergy. The patients treated with B. subtilis showed a significant reduction in frequency and severity of clinical features in respect to the patients who received no treatment. Bacillus subtilis spores may increase S-IgA synthesis or protect gastroenteric mucosa. PMID- 3100072 TI - [Use of an in-line filter for patients with long-term parenteral nutrition]. PMID- 3100073 TI - [Importance of proctological examination in tropical environment. Apropos of 1000 rectoscopies performed at the Hospital of Bamako]. AB - Analysing the results of 1,000 procto-sigmoidoscopies done in Bamako (Mali), the authors asses the major indications of this examination in Africa: rectal biopsy is quite efficient for the diagnosis of schistosomiasis; hemorroides and proctitis are frequent while tumors seem rare. PMID- 3100074 TI - [Neurofibromatosis, the eye and its adnexa. A synthesis]. PMID- 3100075 TI - [Locoregional anesthesia and peroperative ocular immobility]. PMID- 3100076 TI - [Factor VIII concentrates]. PMID- 3100077 TI - [Viral hepatitis: update]. PMID- 3100078 TI - Interleukin-2. PMID- 3100079 TI - The use of quantitative methods in planning national cancer control programmes. A WHO meeting. AB - There is a strong need to allocate in a rational and cost-effective way the available resources for cancer control in countries. Continuation of current priorities in resource allocation can only lead to unnecessarily high incidence, morbidity and mortality from cancer. Two cancer control models for cost effectiveness, which were developed by WHO to help Member States set priorities in national cancer control programmes, have been tested and found useful. This article discusses cost-effectiveness analysis and describes the two models and their application in countries. PMID- 3100080 TI - Pharmacokinetics and metabolism of hexamethylmelamine in mice after IP administration. AB - The pharmacokinetics of hexamethylmelamine (HMM) and its first metabolite (hydroxymethylpentamethylmelamine: HMPMM) following IP bolus dose of 200 mg/kg were studied in mice. The drug concentrations were determined by a sensitive reversed-phase HPLC assay. Thus, for the first time, HMM major hydroxylated and demethylated metabolite plasma levels canbedetermined at the same time. Pharmacokinetic data were analyzed by an original method using a nonlinear cost function minimized by a simplex algorithm. An important property of this computer program is that convergence is ensured in contrast to linear or nonlinear least square regression analysis, which leads to lack of convergence or to false convergence. Both HMM and HMPMM data fit a one-compartment open model. The parameters obtained indicate that the parent drug would probably be rapidly and completely transformed by the human body into HMPMM. PMID- 3100081 TI - Structure/activity relationships of polyfunctional diterpenes of the ingenane type. I. Tumor-promoting activity of homologous, aliphatic 3-esters of ingenol and of delta 7,8-isoingenol-3-tetradecanoate. AB - Eight skin irritant 3-esters with the homologous even number aliphatic acids (acetic to hexadecanoic acid) of the polyfunctional diterpene alcohol ingenol as well as the non-irritant 3-tetradecanoate of delta 7,8-isoingenol were tested for their initiation or (tumor)-promoting activity in the standardized semi quantitative initiation/promotion assay on the back skin of NMRI mice. In a corresponding protocol over 48 weeks without preceding initiation, i.e. as a tumorigen, the 3-hexadecanoate of ingenol (3-HI) proved to be practically inactive as compared to the strong response elicited as promoter. Dose/response relations were shown to be positive for both 3-HI and 3-O-tetradecanoylingenol (3 TI), as representative ingenol-3-esters. In assays for structure/activity relations of promoting activity, it turned out that the group of 3-acetate, 3 butyrate and 3-hexanoate of ingenol are very weak to weak promoters. The group of 3-octanoate to 3-HI proved to be strong promoters. Maximal activity was exhibited by 3-TI and it is proposed that this be considered the prototype of the 3-esters of the ingenane type. In semi-quantitative terms it is slightly less active as a skin tumor promoter than the tigliane type 12-O-tetradecanoylphorbol-13-acetate. At the same dose level as 3-TI, the 3-tetradecanoate of delta 7,8-isoingenol was inactive as a promoter. PMID- 3100082 TI - Localization of aflatoxin B1--nucleic acid adducts in mitochondria and nuclei. AB - The reaction of chemical carcinogens with cellular macromolecules, particularly DNA, is considered to be an important event during chemical carcinogenesis. Until recently, most studies have dealt primarily with nuclear DNA (nDNA). Mitochondrial DNA (mtDNA) is increasingly being investigated for its possible role during chemical carcinogenesis. Using monoclonal antibodies against aflatoxin B1 (AFB1)-modified guanosine and ultrastructural immunocytochemistry, we have localized the AFB1-guanosine adducts predominantly in mitochondria and nuclei. Morphometric analysis of the electron micrographs demonstrates that localization of the AFB1-guanosine adducts is several-fold greater in mitochondria than in the nuclei. However, biochemical analysis demonstrates that 77% of the covalent binding was detected in nucleic acids of the mitochondria relative to the nuclear fractions. In RNA-free preparations, the extent of covalent modification of mt circular DNA was less than 50% of that of nuclear DNA. Our results indicate that 67% of AFB1 binding to mitochondrial nucleic acids is associated primarily with mtRNA. PMID- 3100083 TI - Skin tumor promotion is associated with increased type V collagen content in the dermis. AB - Tumor promotion in mouse skin depends upon establishment of hyperproliferation as well as inflammation and involves disturbance of normal communication between dermis and epidermis. As the collagenous matrix of the dermis is known to play an important role in the maintenance of normal dermal-epidermal interactions, alterations of the dermal collagen types during tumor promotion with 12-O tetradecanoyl-phorbol-13-acetate (TPA) were investigated. In TPA-treated samples no difference between the relative content of type I and III collagen was observed, whereas the content of type V was significantly increased. When TPA treatment was discontinued before tumor development no increase of type V collagen was observed. Furthermore, treatment with the non-promoting mitogens 4-O methyl-TPA and Ca-ionophore A 23187 did not result in any alterations of the matrix composition. These data indicate that the increase of type V collagen content is part of the disturbed tissue interactions between dermis and epidermis that facilitate tumor development. PMID- 3100084 TI - Colony formation enhancement of rat tracheal and nasal epithelial cells by polyacetate, indole alkaloid, and phorbol ester tumor promoters. AB - The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), teleocidin and two polyacetate tumor promoters (aplysiatoxin and debromoaplysiatoxin) have been tested for their effect on colony forming efficiency (CFE) of rat tracheal and nasal turbinate epithelial cells. In rat tracheal epithelial (RTE) cells, all four compounds stimulated colony formation by up to 8-fold using picomolar concentrations of aplysiatoxin and teleocidin, whereas TPA and debromoaplysiatoxin were effective in the nanomolar range. In addition, teleocidin and the other promoters increased the number of cells in colonies by 3 to 5-fold resulting in larger colonies, most notably above concentrations that maximally stimulated CFE. In contrast, rat nasal epithelial cells were only marginally stimulated by these tumor promoters to form colonies. The results indicate that there is regional specificity in responses to tumor promoters and RTE cells can act as very sensitive biological indicators of the presence of these three classes of tumor promoters with diverse structure. PMID- 3100085 TI - Peroxisome proliferator-induced hepatocarcinogenesis: levels of activating and detoxifying enzymes in hepatocellular carcinomas induced by ciprofibrate. AB - It is generally held that altered areas, neoplastic nodules and hepatocellular carcinomas (HCC) induced by mutagenic chemical carcinogens are resistant to the effects of hepatotoxins. This characteristic is attributed to the marked decrease in activating (phase I) enzymes and a several-fold increase in detoxifying (phase II) enzymes. In previous studies, we have shown that hepatic neoplastic lesions induced by non-mutagenic peroxisome proliferators differed from mutagenic carcinogen-induced lesions by lacking gamma-glutamyl transpeptidase and the placental form of glutathione S-transferase. In this study we have examined ciprofibrate-induced HCC for phase I and phase II enzymes. These tumors showed a marked decrease in cytochrome P-450 (53%), cytochrome b5 (79%) and aryl hydrocarbon hydroxylase (55%) activities compared to normal livers. Interestingly, activities of phase II enzymes in these tumors, such as UDP glucuronyltransferases and sulfotransferases were decreased or remained the same as in the normal livers. In addition, the activity of epoxide hydrolase was also decreased markedly in all peroxisome proliferator-induced HCC. The decrease in the activity of various enzymes appears not to be due to the direct effect of ciprofibrate, since no inhibitory effect was observed after adding this compound in vitro. These findings further amplify the differences between the hepatic lesions induced by mutagenic hepatocarcinogens and non-mutagenic peroxisome proliferators suggesting a divergence in the mechanism by which peroxisome proliferators induce liver tumors. PMID- 3100086 TI - 7,12-Dimethylbenz[a]anthracene: refined structure, electron density distribution and endo-peroxide structure. AB - The crystal structure of 7,12-dimethylbenz[a]anthracene (DMBA) has been refined from new X-ray diffraction data collected at low temperature (180 K). This has allowed the location of the hydrogen atom positions not previously reported in earlier structure determinations and refinements; a more precise molecular geometry is therefore now presented. In addition, an analysis of the electron density in this carcinogenic molecule has been made by multipole refinement. These two types of studies give information on the amount of strain in the bay region and the distribution of electron density in the molecule. The molecule is highly distorted in the bay region as a result of steric overcrowding between hydrogen atoms (minimum H ... H 2.06 A) so that torsion angles of 18 degrees and 22 degrees occur in this area. The bonds in the bay region and to the two methyl groups appear to be electron-rich; however, while the K-region of DMBA has a high pi-bond density computed from interatomic distances, the multipole analysis does not indicate that it is highly electron-rich. The 7- and 12-positions (equivalent to the 9- and 10-positions of anthracene) are highly reactive and appear to show a deficiency of electron density. Molecular dioxygen can add across these positions to give a peroxy compound. The crystal structure of such an endo peroxide of DMBA has also been studied at 180 K although not to the high precision obtained for the parent compound. Some distortions are apparent in this molecule; in particular small CH3-C-O angles (101-104 degrees) are observed, indicative of some strain in the molecule. A computer graphics analysis of the diol epoxides of DMBA, generated from X-ray coordinates of DMBA and reported values for a diol epoxide of benzo[a]pyrene, show that steric overcrowding may affect the conformation of certain isomers of the diol epoxides. PMID- 3100088 TI - [Effect of pyquiton on some histochemical activities of schistosomules of Schistosoma japonicum in mice]. PMID- 3100087 TI - Induction of mammary cytochromes P-450: an essential first step in the metabolism of 7,12-dimethylbenz[a]anthracene by rat mammary epithelial cells. AB - Rat mammary epithelial cells (RMEC) in culture have been shown to activate polycyclic aromatic hydrocarbon (PAH) carcinogens. This study investigates the role of mammary cytochrome P-450 monooxygenases in these metabolic processes. Monooxygenation of 7,12-dimethylbenz[a]anthracene (DMBA) by RMEC in culture exhibited a 6-h lag period before reaching a constant rate. The mechanism for this time-dependent expression of DMBA monooxygenase activity was investigated in lysed cells, where both conjugation and in situ induction of P-450 are prevented. Although metabolism of DMBA by untreated RMEC lysates was undetectable (less than 1 pmol/mg cell protein/h), prior exposure of cultured cells to benz[a]anthracene (BA) induced DMBA metabolism, (approximately 100 pmol/mg cell protein/h). BA pretreatment also eliminated the lag period for metabolism of DMBA by cultured RMEC but did not prevent additional induction of DMBA monoxygenase activity by the substrate. The distribution of monooxygenated DMBA metabolites formed by BA induced cell lysates was clearly different from that obtained with purified P 450c, the predominant PAH-inducible isozyme in rat liver. For example, the carcinogen precursor DMBA 3,4-dihydrodiol, which is not formed by P-450c, was a clearly detectable product in RMEC. The low epoxide hydratase activity of BA induced lysate (approximately 400-fold lower compared to that in the liver) limited formation of all DMBA dihydrodiols. The formation of DMBA 3,4-dihydrodiol increased by 5-fold following addition of exogenous purified epoxide hydratase. The DMBA monooxygenase activity of BA-induced RMEC lysates was completely inhibited by alpha-naphthoflavone but was only partially inhibited (50%) by a polyclonal antibody raised against cytochrome P-450c. Anti P-450c completely inhibited formation of some of the metabolites, partially inhibited formation of others and notably stimulated formation of DMBA 3,4-dihydrodiol by 60%. A polyclonal antibody that recognized both rat hepatic P-450a and a group of P-450 isozymes related to P-450h, and which totally inhibited DMBA 3,4-dihydrodiol formation by rat liver microsomes, did not inhibit formation of any DMBA metabolite in RMEC, including DMBA 3,4-dihydrodiol. Western blot analyses of RMEC homogenates demonstrated that BA pretreatment induces P-450c, but not P-450a or any of the P-450h-related isozymes. We conclude that metabolism of DMBA by RMEC depends on induction of P-450c and at least one additional form of cytochrome P 450 which is immunochemically distinct from rat hepatic P-450a and P-450h related isozymes, but is sensitive to alpha-naphthoflavone. PMID- 3100090 TI - [Clinical analysis and treatment of 55 cases of intestinal sarcosporidiosis]. PMID- 3100089 TI - [Radiorenographic study in advanced schistosomiasis. A report of 37 cases]. PMID- 3100091 TI - [The application of biotin-avidin system in the diagnosis of schistosomiasis japonica]. PMID- 3100092 TI - High-affinity monoclonal antibodies specific for human prostatic acid phosphatase. AB - We produced two monoclonal hybridoma cell lines that secrete IgG immunoglobulins with high affinities (Kd = 7.3 to 8.0 X 10(-11) mol/L, Ka = 1.25 to 1.37 X 10(10) L/mol) for 125I-labeled human prostatic acid phosphatase (PAP), and that specifically bind this enzyme from human serum. The antibodies were produced in high titers in murine ascitic fluid (700 mg/L) and in cell-culture media (30 mg/L) and were further purified to homogeneity by affinity chromatography on PAP- and Protein A-Sepharose CL-4B. After purification they were shown to be homogeneous by liquid chromatography. Both of these monoclonal antibodies exhibit strict specificity for PAP as determined by radioimmunoassay and by immunofluorescence studies of human pancreas, kidney, prostate, and leukocytes. The antibodies react only with the native form of the enzyme, as shown by the slot-immunoblotting method. PMID- 3100093 TI - Plasma apolipoproteins in Tangier disease, as studied with two-dimensional electrophoresis. AB - Tangier disease is characterized by a deficiency of high-density lipoproteins and of their major protein constituent, apolipoprotein (apo) A-I. We used high resolution two-dimensional electrophoresis to examine the principal plasma apolipoproteins (A-I, A-II, A-IV, E, C-II, and C-III) of three persons with Tangier disease, one homozygous patient and his two heterozygous children, comparing the patterns with those for healthy subjects. Characteristic abnormalities were found in the distribution of the isoproteins of apo A-I, there being a normal concentration of pro apo A-I but dramatically decreased concentrations of the other apo A-I isoproteins. We also found hitherto undescribed polypeptide abnormalities in apo C-III: sialylated and nonsialylated forms of apo C-III appear as double spots having the same isoelectric points but different molecular masses. No other substantial difference was detected in the polypeptide distribution of the other plasma apolipoproteins. PMID- 3100094 TI - Rate nephelometry and radial immunodiffusion compared for measuring serum prealbumin. AB - We compared a rate-nephelometric method and a radial immunodiffusion (RID) assay for measurement of prealbumin (transthyretin) in 55 samples of serum from healthy children. The mean prealbumin concentration as measured by the Beckman Auto ICS nephelometer was 188 mg/L (range 128-350); the mean by RID was 221 mg/L (range 125-419). This difference was statistically significant by Student's t-test (p less than 0.05), but the correlation coefficient (r) was 0.95. To determine a reference interval for prealbumin in children by the Auto ICS method, we assayed samples from 93 healthy children between the ages of one day and 18 years (55 boys, 38 girls). The mean was 191 mg/L, the reference interval (mean +/- 2 SD) 109-273 mg/L. There was no significant difference in prealbumin concentrations between girls and boys (Student's t-test, p greater than 0.05). Evidently the Beckman Auto ICS method measures prealbumin in serum rapidly and accurately. PMID- 3100095 TI - Enzyme immunoassay of free triiodothyronine in serum. AB - In this new solid-phase antibody enzyme immunoassay for free triiodothyronine (FT3) in serum, beta-D-galactosidase conjugated to triiodothyronine is used. Results are uninfluenced by physiological concentrations of thyroxin-binding globulin or albumin. Results correlate well with those determined by equilibrium dialysis (r = 0.95). The mean CVs within and between assays were 6.1 and 9.5%, respectively. The measurable range of FT3 in serum is 0.7 to 26 ng/L; the normal reference interval is 1.9 to 8.9 ng/L. Concentrations of FT3 in serum of patients with hyperthyroidism were high; those of patients with hypothyroidism were within normal limits or low, and those of patients with congenitally decreased or increased TBG were within the normal range. In normal pregnant women, concentrations of FT3 as determined by radioimmunoassay correlated with those of albumin, declining as pregnancy progressed, but FT3 values determined by the proposed method or equilibrium dialysis were within the normal range and did not change during pregnancy. PMID- 3100096 TI - Underestimation of monoclonal proteins by serum protein electrophoresis on cellulose acetate. AB - Our study of 95 serum samples from 37 patients with monoclonal gammopathy revealed distorted irregular monoclonal (M) protein bands after serum protein electrophoresis (SPE) on cellulose acetate membrane. In 71 (75%) of the 95 sera, the M-protein was underestimated and the albumin concentration overestimated. Dilution of the serum sample before SPE eliminated the abnormality of the M protein bands. By SPE, the mean albumin concentration in these 71 undiluted sera was 45.8 (SD 7.4) g/L vs 37.9 (SD 5.8) g/L for the diluted sera; moreover, this was true of individual samples: measured albumin concentration in each diluted serum sample was always less than in the undiluted serum. As measured by the bromcresol green dye-binding method, the albumin concentration was 32.8 (SD 5.9) g/L. Similarly, the M-protein concentration in SPE was 49.5 (SD 12.3) g/L for the undiluted sera vs 61.8 (SD 15.1) g/L for the diluted sera, and the M-protein concentration in each diluted serum sample always exceeded that in the undiluted serum. Underestimation of M-protein limits the usefulness of M-protein measurement in evaluating the patient's response to therapy and for early detection of disease progression. SPE strips should be carefully inspected visually, and sera with M-protein band abnormalities should be diluted and re assayed if SPE is to quantify concentrations of M-protein and albumin accurately. PMID- 3100097 TI - Quantification of two different types of apolipoprotein A-I containing lipoprotein particles in plasma by enzyme-linked differential-antibody immunosorbent assay. AB - We describe a method for measuring apolipoprotein A-I (ApoA-I) associated and unassociated with apolipoprotein A-II (ApoA-II) in plasma. To directly determine associated ApoA-I, we coated microtiter plates with antibody to ApoA-II, blocked the nonspecific binding sites, and incubated the plate with plasma, immobilizing the lipoprotein particles containing both ApoA-II and ApoA-I. The unbound constituents of plasma were washed away, peroxidase-labeled antibody to ApoA-I was added, the plate rewashed, peroxidase substrate added, and the resulting color measured. ApoA-I unassociated with ApoA-II was evaluated by subtracting the concentration of associated ApoA-I from the total ApoA-I concentration. The method is specific, rapid, and precise. Within- and between-assay CVs were 5.6 and 9.8%, respectively. Analytical recovery of ApoA-I was 94%. The average normolipidemic concentration of ApoA-I associated with ApoA-II in 50 women was 790 mg/L; in 50 men, it was 788 mg/L. The corresponding values for unassociated ApoA-I were 644, 577 mg/L. Both lipoprotein forms of ApoA-I were detected in all major density classes, but were most abundant in high-density lipoproteins. The technique is applicable to measurement of any two apolipoproteins that occur in both associated and unassociated forms in plasma. PMID- 3100098 TI - Europium and samarium as labels in time-resolved immunofluorometric assay of follitropin. AB - This time-resolved immunofluorometric assay for human follitropin involves use of europium- or samarium-labeled monoclonal antibodies, with an average incorporation ratio of 3 mol of Eu3+ or Sm3+ per mole of antibody. These lanthanide ions are bound to the antibody molecules by means of the anhydride of diethylenetriaminepentaacetic acid. The solid-phase antibody is immobilized inside polystyrene tubes in which plasma samples were assayed in a one-step procedure. After incubation, the fluorescence intensity of Eu3+ or Sm3+ label is measured by time-resolved fluorometry, with a nitrogen laser as the pulsed excitation source. The sensitivity of the assay is largely better with Eu3+ than with Sm3+ because of the difference in their intrinsic luminescence properties. Results obtained with the proposed methods correlated well with those by an immunoradiometric method. PMID- 3100099 TI - On the albumin-dependence of measurements of free thyroxin. II. Patients with non thyroidal illness. AB - We studied the relation between thyroxin-binding proteins and free thyroxin (FT4) measurements by five radioimmunoassays (RIA) and an FT4 index (FT4I) in patients with non-thyroidal illness (NTI). The one-step FT4 RIAs and the FT4I frequently failed to identify the true FT4 status (as determined by equilibrium dialysis) of NTI patients. In these patients, falsely low FT4 results with one-step RIAs and FT4I were associated with decreasing total T3 and T4 concentrations, which, furthermore, paralleled decreasing serum albumin concentrations. All NTI patients with "low T3, low T4 syndrome" had subnormal albumin concentration. The two-step RIAs and equilibrium dialysis showed normal FT4 concentrations in most patients with NTI. However, sera from a subset of NTI patients with "low T3 syndrome" gave above-normal FT4 results with these methods. From their predictably poor performance in the presence of a subnormal albumin concentration, we conclude that the one-step FT4 RIAs and FT4I are inappropriate for testing the thyrometabolic status of NTI patients. PMID- 3100101 TI - Isolation and purification of placental type alkaline phosphatase from a seminoma. AB - An alkaline phosphatase (EC 3.1.3.1) of the placental type was isolated from a seminoma type of human testicular cancer tissue and was purified to homogeneity by sulfate-mediated chromatography on a column of Cibacron Blue Sepharose 4B. The purified enzyme had a specific activity of 40.6 kU per gram of protein and was obtained in a yield of 37%. The purification procedure used was simple and economical, and may be used to purify alkaline phosphatase isoenzymes from other cancer tissues. This is the first report of the purification of the enzyme in seminoma. Inhibition studies suggest that this enzyme is a Nagao variant rather than the Regan type reported in several cancer tissues. PMID- 3100100 TI - Simple spectrophotometric determination of urinary albumin by dye-binding with use of bromphenol blue. AB - This procedure for routine quantification of albumin in urine is based on the dye binding properties of albumin with bromphenol blue. The absorbance of 100 microL of urine mixed with 3 mL of color reagent is measured against blank reagent at 610 nm after 30 s. Results vary linearly with albumin concentration up to 6 g/L. The reaction is pH independent in the physiological range. It is not subject to substantial interference by uric acid, creatinine, calcium, sodium chloride, or bilirubin. The presence of globulins produces a small positive error. Within-run precision (CV) was 4.8, 1.5, and 0.9%, and day-to-day precision was 11.2, 2.0, and 1.9%, for samples containing albumin at about 0.1, 1.0, and 6.0 g/L, respectively. Results by a radial-immunodiffusion method (x) correlated well with those by the proposed method (y): r = 0.986; y = 0.98x + 0.096; n = 64. The method can also be used to detect globulins, such as Bence Jones protein, by measuring the ratio of the absorbance at 30 min to that at 30 s. PMID- 3100102 TI - False-positive results for ketone with the drug mesna and other free-sulfhydryl compounds. AB - All free-sulfhydryl compounds tested produced false-positive reactions in the Legal test for ketones. The color developed in the ketone pad of urine dipsticks [N-Multistix SG, Multistix 10 SG (Ames), and Chemstrip 9 (Boehringer-Mannheim)] was misinterpreted for ketone bodies, both by visual and automated reading. In contrast to the reaction with true ketones, a drop of glacial acetic acid added onto the ketone pad of dipsticks discharged the false-positive red color. A red violet also developed instantly with free -SH compounds in the Acetest tablet assay (Ames), but quickly faded. In general, the presence of acidic groups such as -COOH and -SO3H in the structure appeared to increase the nitroprusside reactivity of free -SH compounds, whereas the presence of a -NH2 group appeared to decrease it. Currently, false-positive ketone reactions ascribable to a free SH group are most likely to be seen for urine containing mesna. The false positive test for ketones caused by free -SH compounds can be recognized and ruled out by proper procedures. On the other hand, this chromogenic reaction with free thiols might be used for monitoring urinary excretion of mesna. PMID- 3100104 TI - Radioimmunoassay of apolipoprotein A-I in serum and EDTA plasma, and effects of freeze-thaw cycles. PMID- 3100103 TI - Value and limitations of a highly sensitive immunoradiometric assay for thyrotropin in the study of thyrotroph function. AB - Using a highly sensitive and specific immunoradiometric assay for thyrotropin, we studied thyrotroph function in 232 new patients referred to a thyroid clinic and in 13 patients after treatment for hyperthyroidism. Significant thyrotroph responsiveness to thyroliberin (thyrotropin-releasing hormone, TRH) was found in all patients with values for basal thyrotropin greater than 0.1 milli-int unit/L. In no overtly hyperthyroid patient was any increment in thyrotropin recorded at 20 min after thyroliberin administration. In seven patients, four subclinically hyperthyroid and three who had received treatment, increments in thyrotropin from undetectable basal values were recorded, consistent with incomplete thyrotroph suppression. By use of assays with even higher sensitivity, one may be able to distinguish these patients from overtly hyperthyroid patients. PMID- 3100105 TI - Apolipoprotein profile in healthy males and its relation to maximum aerobic capacity (MAC). AB - In order to document possible variations of apolipoproteins in relation to the maximum aerobic capacity, 36 healthy young males of different aerobic performance were examined and the serum concentrations of apolipoprotein A-I, A-II, B, C-II, C-III, E investigated. In contrast to all other lipoproteins, significant differences between the endurance-trained and control subjects could be found in the apo A-I concentrations only (1025 +/- 92 vs 1456 +/- 179 mg/l, p less than 0.001). In addition, the apolipoprotein A-II, B, C-II, C-III, E concentrations correlated neither with the maximum aerobic capacity values nor with the relative body weight of the subjects. PMID- 3100107 TI - Single radial immunodiffusion of serum apolipoproteins C-II, C-III and E- pretreatment of samples with surfactant. AB - An assay of apolipoproteins (Apo) C-II, C-III and E in human sera by single radial immunodiffusion (SRID) is described. The procedure involves pretreatment of the serum sample with surfactant to facilitate diffusion of very low density lipoproteins in agarose. This allowed measurement of apolipoproteins in lipidemic sera by SRID in agarose gel. The intraplate coefficient of variation was less than 2.5%, and the interplate coefficient of variation, less than 3.0%. Correlation with double-antibody radioimmunoassay produced the following coefficients of correlation: gamma = 0.9931 (n = 17) for Apo C-II, gamma = 0.9221 (n = 33) for Apo C-III, and gamma = 0.9340 (n = 17) for Apo E. PMID- 3100106 TI - Effect of fenoprofen on thyroid function tests. AB - We observed that a few patients taking the anti-inflammatory drug fenoprofen showed increases in total and free T3 serum levels without convincing evidence of an associated thyrotoxicosis. To confirm these findings, two volunteers were given fenoprofen for two weeks. Within this time total T3 levels almost doubled and free T3 levels increased threefold. Administration of fenoprofen did not have any measurable effect on T4 or TSH estimations. Cross-reactivities of fenoprofen and 4'-hydroxyfenoprofen were studied with antisera from various total and free T3 assays. Results show that the metabolite cross-reacts with the antisera from Amerlex total and free T3 assay kits. A lesser degree of interference was observed with the Corning total and free T3 assays. 4'-hydroxyfenoprofen had no effect on an 'in house' total T3 assay. Laboratories should therefore be aware of the possibility that their assay may be subject to interference by fenoprofen or its metabolites while clinicians should be aware of this interference in order that they may avoid unnecessary and harmful treatment. PMID- 3100108 TI - Membrane lipid peroxidation in erythrocytes of the newborn. AB - Fresh, untreated neonatal erythrocytes contained nearly two times the adult level of thiobarbituric acid-reactivity, an index of lipid peroxidation. In addition, both fluorescence and the phospholipid:MDA adduct were significantly increased in neonatal erythrocytes. This study suggests that neonatal erythrocytes undergo significant peroxidative membrane lipid damage in vivo. PMID- 3100109 TI - A novel alkaline phosphatase isozyme in human adipose tissue. AB - A novel alkaline phosphatase (AP) isozyme was found in human adipose tissue. Adipose tissue alkaline phosphatase differed in enzymatic properties from liver, placental and intestinal alkaline phosphatases. On electrophoresis it showed the same mobility as intestinal alkaline phosphatase, but after treatment with neuraminidase its mobility was decreased to the same as or slightly less than that of neuraminidase-treated liver alkaline phosphatase. Its inhibition by amino acids, inactivation by urea and activation by Mg2+ were almost the same to those of liver alkaline phosphatase. However, at 56 and 65 degrees C it was more stable than liver alkaline phosphatase. Alkaline phosphatase activity was demonstrated histochemically in adipose tissue with naphthol AS-MX phosphate as substrate. It was localized in the wall of blood capillaries, but not present in adipocytes. PMID- 3100111 TI - Hypothalamic function in women with secondary hypogonadism and unresponsive to clomiphene therapy. AB - Seven women with secondary hypogonadism who had been previously unresponsive to two 5-d courses of clomiphene citrate, were treated with clomiphene citrate 100 mg daily for 10 d. LH and FSH concentrations were measured in serum collected at 15-min intervals for 5 h before and on the 10th day of treatment and oestradiol was measured in the first two samples on each day. Four women responded with an increase in the amplitude of LH pulses and in mean LH values and in three there was a marked increase in serum oestradiol concentrations. Three women who showed no gonadotrophin response were subsequently unresponsive to pulsatile LHRH therapy. These preliminary data are consistent with the hypothesis that hypothalamic hypogonadotrophism may result from hypersensitivity of the hypothalamus to oestrogen negative feedback and that the hypothalamic potential for secretion of LHRH is unimpaired. Prolonged treatment with clomiphene may provide a simple test of hypothalamic function in women with normal pituitary function. PMID- 3100110 TI - Growth hormone pretreatment in man blocks the response to growth hormone releasing hormone; evidence for a direct effect of growth hormone. AB - The effect of pretreatment with biosynthetic methionyl human GH (hGH) on the GH response to GHRH has been studied in normal subjects. Eight volunteers were given either 4 IU hGH or placebo s.c. 12-hourly for 72 h before a GHRH test, or a single s.c. dose of 4 IU hGH 12 h before a GHRH test. Somatomedin-C (Sm-C) levels at the time of the GHRH tests were significantly elevated after treatment with hGH compared to placebo, and the GH response to GHRH was significantly attenuated. A further six subjects were given 2 IU hGH or placebo i.v., and i.v. GHRH 3 h later; there was no rise in Sm-C for the 5 h of the study after either treatment; nevertheless, the response to GHRH was completely abolished by pretreatment with hGH. These results demonstrate that GH can regulate its own secretion independently of changes in Sm-C levels, through a mechanism other than the inhibition of GHRH release. The attenuated response to GHRH in the presence of elevated Sm-C levels may be related to Sm-C, or be a more direct effect of the recently elevated GH levels. PMID- 3100112 TI - Iodide administration enhances thyrotrophin responsiveness to thyrotrophin releasing hormone during fasting: evidence for normal pituitary feedback regulation. AB - Short-term fasting in humans is associated with diminished delta TSH to TRH. The purposes of the present study were to reassess basal TSH levels and TRH responsiveness during fasting utilizing a sensitive radioimmunoassay (RIA: sensitivity 0.3 microU/ml; normal range 0.66-2.98 microU/ml) and to determine if normal feedback regulation is maintained during the fasting state. Eight control subjects (C) and six iodide-treated (I) subjects (262 mg/d) were studied in the fed state and on day 10 of fasting. T3, T4, and TSH were measured by RIA, and free T4 and free T3 by equilibrium dialysis. Basal serum TSH levels in the control group were 2.0 +/- 0.3 microU/ml (mean +/- SEM) in the fed state and increased to 14.7 +/- 3.5 microU/ml 20 min after TRH administration. The fasting basal TSH level of 1.6 +/- 0.3 microU/ml was significantly decreased (P less than 0.01) compared to control, as was the level of 8.8 +/- 2.3 microU/ml (P less than 0.01) obtained 20 min after TRH. In the iodide-treated group the basal TSH level was 1.4 +/- 0.2 microU/ml during feeding which increased (P less than 0.025) to 2.9 +/- 0.7 microU/ml during fasting; the TSH value 20 min after TRH was 12.6 +/- 2.5 microU/ml while feeding and 17.3 +/- 2.9 microU/ml while fasting. Free and total T3 decreased during fasting in both groups. Total T4 was unchanged between the fed and fasted periods in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100113 TI - Full expression of Hunter's disease in a female with an X-chromosome deletion leading to non-random inactivation. AB - A 2.5-year-old girl who presented with abdominal distension, hepatomegaly, coarse facies, hirsutism and contraction deformities was investigated for mucopolysaccharidoses. Urinary excretion showed increased total glycosaminoglycans (105 mg/mmol creatinine; normal for age 9-20 mg/mmol) with marked increases of dermatan and heparan sulphates. A number of lysosomal enzyme activities were measured on leucocytes, serum and cultured fibroblasts. Normal or high activities were found for alpha-iduronidase, N-acetylgalactosamine-6 sulphatase, beta-galactosidase, arylsulphatase B and beta-glucuronidase. However a marked deficiency of iduronate sulphate sulphatase activity was observed, consistent with a diagnosis of Hunter's disease. Activities were reduced to less than 2% of mean control values in the patient's leucocytes, serum and cultured fibroblasts. Normal activities were measured in samples from the father and younger sister but a partial deficiency (43% of control serum) was found in the mother. Chromosome studies on the patient revealed a partial deletion of the long arm of one X-chromosome, most probably of band Xq25, which was not inherited from either parent. Studies using BrdU indicated that the deleted X chromosome was consistently late replicating, and as a result the Hunter gene was fully expressed on the other X chromosome. PMID- 3100114 TI - Multiple sulphatase deficiency presenting at birth. AB - A new case of multiple sulphatase deficiency with onset at birth is described. The patient had many dysmorphic features and hydrocephalus, similar to one other case with early onset described in the literature. The new patient differed from the other case in having chondrocalcificans congenita, heart abnormalities and an abnormal fold of tissue present between the laryngeal inlet and the oesophagus. Excessive mucopolysacchariduria was present and there was profound deficiency of all sulphatases examined in plasma, leucocytes and cultured skin fibroblasts. PMID- 3100115 TI - Studies on the accessory requirement for T lymphocyte activation by concanavalin A. AB - In this study we have examined the interactions between accessory cells (AC) and T cells in response to Con A. Highly purified peripheral blood T cells and AC exposed to a variety of treatments were used. We found that untreated AC provided optimal help for T cell proliferation and this was not mediated by soluble factors since whole cells could not be replaced with supernatants from activated AC. Furthermore, cycloheximide-treated AC were able to supply the accessory signal although unable to elaborate soluble activation factors. To find out more about the accessory signal, we examined the ability of monocytes mildly fixed with glutaraldehyde to supply help. These cells were completely unable to perform as AC, although they were viable and had unaltered surface antigen expression. They could not secrete activation factors, but this alone could not explain their inability to supply help because this function was not restored with the addition of soluble activation factors. This indicated that AC-T cell contact was of prime importance to accessory function. To investigate the possibility that AC work by cross-linking structures on the lymphocyte surface, we attempted to substitute for the soluble Con A plus AC with Con A bound to the surface of erythrocytes. Comparable stimulation was observed, suggesting that the cross-linking of Con A bound structures on the lymphocyte surface generates the accessory signal. PMID- 3100116 TI - Effects of in-vivo administration of a monoclonal antibody specific for the interleukin-2 receptor on the acute graft-versus-host reaction in mice. AB - Parental strain T lymphocyte injected into F1 mice respond to allogeneic MHC antigens and so induce the symptoms of a graft-versus-host reaction (GVHR). We have measured the local GVHR by the popliteal lymph node assay, and showed the suppression of the local GVHR in mice by treatment with the monoclonal antibody (MoAb) AMT-13 which is specific against the interleukin 2 (IL-2) receptor on activated mouse lymphocytes. The inhibitory effect of the AMT-13 administration was comparable with the suppression of the local GVHR by treatment with L3T4, an MoAb directed against the T helper subset. The L3T4 administration caused a dramatic decrease in the proportion of the cells with the L3T4 phenotype in the circulation and a marginal reduction of these cells in the lymph nodes. In contrast, the AMT-13 treated mice showed no changes in the distribution of the T lymphocyte subsets besides those in the GVHR-stimulated lymph nodes. Obviously, only the small subset of antigen-activated IL-2 receptor-bearing lymphocytes was influenced by treatment with AMT-13. MoAb directed against antigens whose expression is restricted to activated lymphocytes, such as the IL-2 receptor, might become useful for a short term immunosuppression with limited side effects. PMID- 3100117 TI - Mitogenic response of human thymocytes: identification of functional Ca2+ dependent and independent signals. AB - In contrast to peripheral blood mononuclear cells (PBMC), human thymocytes do not exhibit a proliferative response to the T cell mitogens phytohaemagglutinin (PHA), concanavalin A (Con A), or Staphylococcal protein A (SPA). In thymocytes and PBMC, Con A and PHA induce increases in free cytosolic calcium concentrations [( Ca2+]i). Since both Con A and PHA induce similar increases in [Ca2+]i in thymocytes and PBMC, the absence of thymocyte proliferation was not due to an inability to induce an increase in [Ca2+]i. The lack of proliferative response was secondary to the failure of the mitogens to induce interleukin 2 (IL-2) production. Incubation of mitogen-treated thymocytes with phorbol esters reconstituted IL-2 production and the proliferative response indicating that the cells were indeed activated by the mitogens. Similarly, addition of exogenous recombinant IL-2 also induced mitogen-treated thymocytes to proliferate. This IL 2-dependent proliferation established that SPA, Con A, and PHA triggered the expression of biologically active IL-2 receptors. Since an increase in [Ca2+]i is a prerequisite, and possibly a trigger, for IL-2 production, the failure of PHA, Con A, or SPA to result in thymocyte proliferation may be due to an inability of thymocytes to respond to increases in [Ca2+]i with subsequent IL-2 production. PMID- 3100118 TI - Agglutination of intravenous lipid emulsion ('Intralipid') and plasma lipoproteins by C-reactive protein. AB - Isolated human C-reactive protein (CRP), or CRP in acute phase serum, produced in vitro agglutination ('creaming') of the intravenously administered lipid suspension 'Intralipid'. CRP also produced similar agglutination of isolated normal very low density lipoproteins (VLDL). Agglutination in both cases was calcium-dependent and inhibitable by phosphoryl choline. These findings have important implications for patients receiving intravenous lipid suspensions and may be relevant to the pathogenesis of the fat embolism syndrome following trauma. PMID- 3100119 TI - Detection of anti-histone activity in sera of patients with monoclonal gammopathies. AB - Sera from 249 patients with monoclonal gammopathies (85 multiple myeloma, 92 benign monoclonal gammopathies, 53 cryoglobulinemia, 19 Waldenstrom's macroglobulinemia) were examined for the presence of anti-histone activity. Thirty-four sera were found positive. In 12 of these cases the serum monoclonal immunoglobulins were purified and in all, the anti-histone activity appeared to reside in the monoclonal component. None of the patients had symptomatology of lupus despite high titers of anti-histone activity. This study demonstrates an anti-histone activity of monoclonal components of patients with monoclonal gammopathies. PMID- 3100120 TI - High-dose intravenous gammaglobulin for membranous nephropathy. PMID- 3100121 TI - Postpatellectomy extensive ossification of patellar tendon. A case report. AB - Ossification in the quadriceps mechanism after total patellectomy is a common finding. The relationship of knee symptoms and the extent of postpatellectomy ossifications is debatable. Reported is the case of a 74-year-old woman with extensive ossification in the patellar tendon following patellectomy and knee arthroplasty. The ossification was associated with only minimal discomfort. Functional results following patellectomy were not affected in patients previously observed by the authors. PMID- 3100122 TI - Differences between lactase deficient and non-lactase deficient women with spinal osteoporosis. AB - Both osteoporosis and lactase deficiency are seen commonly in the United States. Since the latter may lead to avoidance of calcium sources and may exacerbate the bone disease in populations at risk, we studied lactose tolerance and histomorphometrically analyzed undecalcified transiliac bone biopsies in a consecutive group of postmenopausal women with the osteoporotic spinal compression fracture syndrome. Oral lactose tolerance tests prior to the biopsy clearly separated two groups. Sixty-five percent had abnormal test results. The bone biopsies in the lactase deficient group showed more osteoid volume and osteoid seam widths on examined trabecular bone. Analysis of tetracycline-labeled bone revealed significant increases in both single, double, combined single and double tetracycline labels, and the percent osteoid labeled with tetracycline. There was no difference in the calcification rates. These findings indicate different mineralization activity in lactase deficient patients, possibly reflecting their lower dietary calcium intake. PMID- 3100123 TI - Effect of disodium etidronate (EHDP) on bone ingrowth in a porous material. AB - This study evaluated the effect of disodium etidronate (EHDP) on biomechanical and histologic characteristics of bone ingrowth in a porous material. EHDP was administered parenterally to six adult mongrel dogs at a dose of 2 mg/kg/day for eight weeks. Six additional dogs served as controls and were injected with saline. Porous titanium fiber composites were inserted into the proximal humeri and the left olecranons of all animals after the first four weeks of treatment. Upon completing a total of eight weeks of treatment, all animals were sacrificed and the bone-porous implant interfacial shear strength was determined by a pull out test to failure. Mean shear strength of fixation for the EHDP-treated group was reduced by 76% compared to the control group (p less than 0.001). Bone ingrowth was mineralized in all of the control specimens. Mineralization of tissue ingrowth was inhibited, however, in all specimens from EHDP-treated animals. These findings suggest that cementless skeletal fixation of porous coated implants by bone ingrowth may be delayed or prevented by the administration of EHDP. PMID- 3100124 TI - Hemorrhagic pancreatitis in a young child following valproic acid therapy. Clinical and ultrasonic assessment. AB - Hemorrhagic pancreatitis was diagnosed with portable realtime ultrasound in a critically ill 4-year-old child. The ultrasonic features were diffuse pancreatic enlargement, generally and focally increased pancreatic echogenicity, and ascites. Ultrasound was indispensable as a portable noninvasive imaging modality that allowed for rapid and accurate diagnosis. PMID- 3100125 TI - [Clinical study of a new nitroglycerin spray preparation in patients with exertion stable angina]. PMID- 3100126 TI - Antimicrobial activity of LY164846, a new oral cephalosporin, and recommendations for disk diffusion tests. AB - LY164846 is a new oral cephalosporin with a limited spectrum of antimicrobial activity that includes staphylococci (other than methicillin-resistant), streptococci (other than enterococci), Haemophilus influenzae (beta-lactamase negative and beta-lactamase-positive), Branhamella catarrhalis (beta-lactamase negative and beta-lactamase-positive), and Neisseria species (beta-lactamase negative and beta-lactamase-positive). The tentative recommendations for susceptibility breakpoints are less than or equal to 4 micrograms/ml and greater than or equal to 19 mm for susceptible, 8 micrograms/ml and 15-18 mm for intermediate, and greater than or equal to 16 micrograms/ml and less than or equal to 14 mm for resistant. PMID- 3100128 TI - Role of nutrition in immune system diseases. PMID- 3100127 TI - Ceftazidime and amikacin alone and in combination against Pseudomonas aeruginosa and Enterobacteriaceae. AB - The efficacy of ceftazidime alone and combined with amikacin was studied in a rabbit model simulating closed-space infections at locally neutropenic sites. Six strains of Pseudomonas aeruginosa, and six Enterobacteriaceae (two strains each of Klebsiella pneumoniae and Serratia marcescens and one strain each of Escherichia coli and Citrobacter freundii) in pooled rabbit serum were each inoculated into separate subcutaneous semipermeable chambers. Intramuscular antibiotic therapy was begun 4 hr later with ceftazidime (50 mg/kg) alone and combined with amikacin (15 mg/kg) for Enterobacteriaceae or ceftazidime (100 mg/kg) alone and combined with amikacin (15 mg/kg) for pseudomonads every 6 hr for 16 doses. Amikacin alone was ineffective for all 12 strains. Ceftazidime alone was successful (greater than or equal to 5.5 log10 colony forming units (CFU)/ml decrease from drug-free control) in eliminating five of six Enterobacteriaceae but was not successful against any of the pseudomonads. Ceftazidime plus amikacin was successful against the same five of six Enterobacteriaceae and five of six pseudomonads. The best in vitro tests for the prediction of in vivo outcome were high inoculum (greater than or equal to 7 log10 CFU/ml) susceptibility, checkerboard synergism testing, and conventional inoculum time-kill rates at concentrations of antimicrobials simulating extravascular levels obtained in vivo. PMID- 3100129 TI - Nutritional problems of institutionalized and free-living elderly. PMID- 3100130 TI - Effects of fiscal retrenchment on public mental health services for the chronic mentally ill. AB - In reviewing the public mental health services of 11 California counties during a period of fiscal retrenchment, we found several common trends: a greater focus on the severely mentally disabled; an increase in utilization of hospital-based care, residential treatment, day treatment, and case management services; and a decrease in the capacity of traditional outpatient services. Although the severely mentally disabled are receiving a higher priority for service, the findings imply that these service systems continue to inadequately address the need for long-term maintenance and supportive services to this population. PMID- 3100131 TI - Distinct fixation of defined amounts of complement by the Brucella abortus antigen and bovine antibodies under different incubation conditions in the CFT. AB - Different times and temperatures of the 1st phase incubation of the complement fixation test (CFT) were used. It was found that a similar decrease in complement (C') activity occurred after 2 h at 37 degrees C, after 8 h at 20 degrees C and after 18 h at 4 degrees C. Simultaneously, in the same periods a double increase in standard serum titre at 4 and 20 degrees C was noted in comparison with titre at 37 degrees C. This increase of sensitivity of the CFT at 4 and 20 degrees C appeared to be a simulating one and resulted from the different pattern of reaction in each temperature in the block titration of antigen. The positive reactions in the range from the lowest to the highest dilutions of antigen were appearing and increasing and then disappearing in sequence at 4, 20 and 37 degrees C, creating the typical C' fixation area for each temperature. Similar results were obtained in four different C' fixation techniques, most frequently used in diagnosis of animal brucellosis. On the basis of our own examination results and literature data the warm and short C' fixation (37 degrees C, 30 min) was chosen in the standard technique of the CFT used in routine diagnostic survey for animal brucellosis in Poland. PMID- 3100132 TI - Gonadal function in patients with acute and chronic renal failure. PMID- 3100133 TI - Thyroid function in renal failure. PMID- 3100134 TI - Endogenous plasminogen activator and venous flow: therapeutic implications. AB - This study is concerned with the changes in endogenous plasminogen activator (PA), in response to the augmentation of venous blood flow by external pneumatic compression (EPC). EPC was applied to the left leg in ten patients undergoing surgery under general anesthesia. Two-ml samples of venous blood were obtained from the left and right femoral veins and an arm vein at baseline (induction), and then at 30 and 60 min of compression. Ninety samples were analyzed in duplicate in a single blind technique, using an assay specific for PA activity. In the control right arm and leg, PA activity levels increased at 30 min (106% and 110% of baseline, respectively), and then declined to baseline levels by 60 min. These changes did not reach statistical significance. In the leg undergoing compression, however, PA activity decreased progressively, reaching 75% of baseline at 60 min (significant at both 30 [p less than .001] and 60 min [p less than .01] as compared to baseline). In vitro, PA activity varies directly with the concentration of fibrin. The progressive decline in activity in this study may, therefore, represent a decline in substrate (molecular fibrin), as a result of increased venous blood flow. Alterations in the activity of the endothelial cell, as observed, may lead to new approaches in the prophylaxis against thromboembolism. PMID- 3100135 TI - Nitroglycerin-induced decrease of carbon monoxide diffusion capacity in acute myocardial infarction reversed by elevating legs. AB - Hemodynamic and respiratory variables were measured in 18 supine patients with acute myocardial infarction uncomplicated by left ventricular failure. Measurements were done during a control period and then when pulmonary capillary bed filling was decreased by iv injection of 3 mg nitroglycerin (NTG) and finally when pulmonary capillary bed filling was increased by raising the patients' legs. Heart rate increased significantly (p less than .05) ventricular filling, and mean aortic pressures dropped significantly (p less than .001) after NTG injection. Heart rate and mean aortic pressure returned to control level and ventricular filling pressures increased significantly (p less than .001) after elevating patients' legs. Mean carbon monoxide diffusion capacity decreased significantly (p less than .01) from 9.8 +/- 3.4 to 8.5 +/- 2.9 ml/min X mm Hg after NTG injection and increased significantly (p less than .02) to 9.3 +/- 3.5 ml/min X mm Hg after elevating patients' legs. Pulmonary wedge pressure decreased significantly (p less than .001) from 15 +/- 5 to 8 +/- 4 mm Hg after NTG injection and increased significantly (p less than .001) to 10 +/- 4 mm Hg after elevating patients' legs. We conclude that NTG reduces pulmonary capillary filling and pulmonary diffusion by reducing the available pulmonary gas exchange surface. PMID- 3100136 TI - Indirect calorimetry in the mechanically ventilated patient. AB - We used indirect calorimetry to measure oxygen consumption (VO2) and carbon dioxide production in 29 mechanically ventilated patients. These data were compared to VO2 measured simultaneously by a standard thermodilution technique. A good correlation was demonstrated between the methods, but VO2 measured by indirect calorimetry was 15% higher than VO2 measured by thermodilution. PMID- 3100137 TI - Predictive value of the stomach wall pH for complications after cardiac operations: comparison with other monitoring. AB - The ability to predict impending complications after elective cardiac operations from measurements of BP, cardiac index, arterial pH, and urine output on the day of operation was compared with that of indirect measurement of stomach wall pH in 85 patients. We found that acidosis in the stomach wall was the most sensitive predictor for complications. The specificity of this predictive test increased exponentially as the duration and degree of intramural acidosis increased. Hypotension, acidosis, and oliguria, but not cardiac index, also predicted postsurgical problems. Stepwise logistic regression analysis of the data that showed postoperative complications were best predicted by the duration of hypotension, and the predictive ability was significantly improved when the duration of intramural acidosis was included. PMID- 3100139 TI - Arterial thrombosis causing cerebral edema in association with diabetic ketoacidosis. PMID- 3100138 TI - Hypercapnia during total parenteral nutrition with hypertonic dextrose. PMID- 3100140 TI - Response of pancreatic tumor to intraoperative radiotherapy: medical imaging and pathologic system approach. AB - For analyzing the local reaction of pancreatic carcinoma to electron intraoperative radiotherapy, successive computed tomography scanning for tumor volumetry was employed, together with surgical clip localization for tumor area using orthogonal x-rays. Soon after radiotherapy the tumor volume and clipped tumor region began to decrease. After a certain interval, computed tomography volumetry revealed that the irradiated tumor had started to increase in size again, whereas the clipped area had not. Autopsies demonstrated that the increase related chiefly to cancer regrowth outside the primary radiation field. PMID- 3100142 TI - Effects of storage and incubation conditions on human granulocyte phagocytic, bactericidal, and chemotactic functions. AB - This study was undertaken to determine the effects of different incubation conditions on human granulocyte (PMN) bactericidal, phagocytic, and chemotactic functions. Specifically, (1) how long may a patient's blood be held before assay and maintain original PMN function, and (2) how long may isolated PMNs be incubated for the purpose of exposure to various agents and still maintain original function? PMNs isolated following storage of whole heparinized blood at 4 degrees C for 24 and 48 hr phagocytized as well as fresh cells and their bactericidal activity was 96 and 85% of control values after 24 and 48 hr, respectively. Chemotaxis decreased to 62% of control after 24 hr. The bactericidal capacity of isolated PMNs stored at 4 degrees C for 24, 48, and 72 hr decreased to 85, 81, and 78% of controls, respectively. Phagocytosis after 24 hr storage was equal to controls. Chemotaxis was decreased to 59 and 34% of controls after 24 and 48 hr, respectively. Isolated PMNs incubated at 37 degrees C demonstrated impairment in phagocytic capacity after only 4 hr. PMID- 3100141 TI - Posterior longitudinal ligament ossification myelopathy and hypothyroidism. AB - Two elderly white women with a long history of hypothyroidism and myelopathy showed ossification in posterior longitudinal ligament at their cervical spine. Case histories are presented and the reported association of PLLO with other conditions discussed. PMID- 3100143 TI - Immunocytochemical localization of chondroitin sulfates in the interphotoreceptor matrix of the normal and dystrophic rat retina. AB - The interphotoreceptor matrix (IPM) is a mixture of proteoglycans and glycoproteins through which metabolites must pass in transit between the retinal pigment epithelium (RPE) and the photoreceptor cells. In order to localize various species of chondroitin sulfates in the IPM of the normal and dystrophic rat retina, we have used monoclonal antibodies directed against 6-sulfated chondroitin sulfate (6S), 4-sulfated chondroitin sulfate (4S) and unsulfated chondroitin (0S). Immunofluorescence and immuno-peroxidase methods were carried out on frozen and wax-embedded sections of rat eyes. In the normal rat retina, strong labeling with the 6S antibody was observed in the basal IS/OS zone and, to a lesser extent, in the photoreceptor interstices extending to the apical RPE surface. In the RCS retina, the IPM in the basal IS/OS zone and much of the outer segment debris zone were labeled intensely with 6S antibody, but no strong labeling was present at the apical RPE surface. The labeling pattern with 0S antibody was similar to that of the 6S antibody for both normal and RCS retinas. We failed to detect any 4S antibody labeling of the IPM in both the normal and RCS retinas using these methods. These results indicate that in the rat retina, the IPM contains 6-sulfated chondroitin sulfate and unsulfated chondroitin proteoglycans that are most concentrated in the basal IS/OS zone and, to a lesser degree, between the photoreceptor outer segments. Furthermore, it appears that the rat IPM contains little or no 4-sulfated chondroitin sulfate or dermatan sulfate proteoglycan. PMID- 3100144 TI - Thermochemical characterization of T-lymphoma cells under non-growing conditions. AB - Cultured T-lymphoma cells, CCRF-CEM, were studied under non-growing conditions by microcalorimetry. A new stirred reaction vessel, mainly designed for biological experiments, was used. The calorimetric results were interpreted by use of known enthalpy data and an assumed net reaction scheme. Of the thermal power measured, 75% could be accounted for by formation of lactate and bicarbonate from the glucose in the medium. It is suggested that the residual power comes from oxidation of intracellular material. PMID- 3100145 TI - Hemodynamic effects of intravenous isosorbide dinitrate and nitroglycerine in acute myocardial infarction and elevated pulmonary artery wedge pressure. AB - We compared in a randomized fashion the hemodynamic effects of intravenous (IV) isosorbide dinitrate (ISDN) and nitroglycerine (NTG) in 45 patients with acute myocardial infarction and elevated pulmonary artery wedge pressure (Paw). Titration of ISDN dose to lower Paw greater than or equal to 25 percent resulted in a fall of this parameter from 32 +/- 8 to 24 +/- 5 mm Hg and was associated with a fall in mean blood pressure (96 +/- 15 to 90 +/- 14 mm Hg, p less than 0.05), systemic vascular resistance (1715 +/- 572 to 1548 +/- 414 dynes X s X cm 5, (p less than 0.05), pulmonary vascular resistance (182 +/- 106 to 154 +/- 78 dynes X s X cm-5, p less than 0.05) and mean right atrial pressure (11 +/- 4 to 7 +/- 4 mm Hg, p less than 0.05). In addition, ISDN significantly (p less than 0.05) increased cardiac index from 2.37 +/- 0.54 to 2.54 +/- 0.59 L/min/m2, stroke volume index from 28 +/- 8 to 31 +/- 8 ml/m2, and stroke work index from 28 +/- 11 to 31 +/- 12 g X m/m2. The ISDN dose ranged from 50 to 533 micrograms/min (mean +/- SD 326 +/- 176 micrograms/min) and could not be predicted from baseline hemodynamic values. A comparison between the effect of ISDN and NTG in doses producing comparable reduction in Paw showed similar hemodynamic changes. It was concluded that IV ISDN in patients with elevated mean pulmonary artery wedge pressure due to acute myocardial infarction results in a decrease in right and left ventricular preload and afterload and improvement of cardiac output and cardiac work. The effective dose ranges from 50 to 533 micrograms/min and cannot be predicted from baseline hemodynamic values. In doses producing comparable reduction in Paw, ISDN and NTG had similar hemodynamic effects. PMID- 3100146 TI - Energy expenditure in patients with chronic obstructive pulmonary disease. AB - Energy expenditure was studied in ten patients with chronic obstructive pulmonary disease (COPD) and weight loss, and in five malnourished patients without clinical evidence of COPD (control group) prior to and after a two-week refeeding regimen. Patients received 5 percent dextrose solution (plus electrolytes) for 36 hours to establish standard baseline conditions and were then randomly assigned to either a carbohydrate-based (CB; 53 percent of calories) or fat-based (FB; 55 percent of calories) diet for the first week. The alternate diet was given the following week. Total calorie intake was set at 70 percent above the energy expenditure measured prior to institution of nutritional support. During energy repletion, energy expenditure was greater than predicted (116 percent) in patients with COPD and less than predicted (90 percent) in the control patients. Thermic effect of nutrients during administration of either regimen was significantly greater (p less than .05) in patients with COPD than in those without COPD during both diets. The difference between the two groups was enhanced during the CB regimen. These observations suggest that malnourished patients with COPD have an elevated resting energy expenditure, and an enhanced thermic response to nutrients as compared to malnourished patients without COPD. Increased diet-induced thermogenesis may contribute to weight loss in patients with COPD, in addition to factors previously described such as decreased caloric intake and increased resting energy expenditure. PMID- 3100147 TI - In vitro activity of SCH-34343, a new penam, and other antimicrobial agents against clinical isolates from cancer patients. AB - The in vitro activity of SCH-34343, a new penam antibiotic, was tested against gram-positive and gram-negative isolates from cancer patients, and compared to that of 7 other antimicrobial agents. SCH-34343 was extremely active against the Enterobacteriaceae with MIC90 ranging from 0.39 to 6.25 micrograms/ml for Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus spp. and Serratia marcescens. It was less active against Acinetobacter spp. (MIC90 6.25-12.5 micrograms/ml) and had poor activity against Pseudomonas aeruginosa. Among gram-positive isolates group A and G beta-hemolytic Streptococci were extremely susceptible to SCH-34343 (MIC90 0.025-0.05 micrograms/ml). Good activity against methicillin-susceptible coagulase-positive and coagulase-negative Staphylococci and Listeria monocytogenes, and moderate activity against Enterococci was also seen. PMID- 3100148 TI - HLA-A, B antigens and the relation between high myopia and high myopia with glaucoma. PMID- 3100149 TI - Experience in surgical management of drug-resistant pulmonary metastatic choriocarcinoma. PMID- 3100150 TI - Choledochoduodenal fistula: a rare complication of duodenal ulcer. PMID- 3100151 TI - Radiologically occult cancer of the peripheral region of the lung. PMID- 3100153 TI - The stomach cancer mortality rate in Beijing urban area (1974-1983). PMID- 3100152 TI - A strain of multiform Cryptococcus neoformans. PMID- 3100154 TI - Application of the enhancement technique of pseudocolor imaging in roentgenodiagnosis. PMID- 3100155 TI - Study on antimicrobial resistance and transferable resistance of Salmonella strains. PMID- 3100156 TI - In vitro cultivation of Schistosoma japonicum schistosomula. PMID- 3100157 TI - Amiodarone in the treatment and control of tachyarrhythmias. PMID- 3100158 TI - Marfan syndrome in Chinese. PMID- 3100159 TI - Low-dose ARA-C in acute leukemias. Analysis of 30 cases. PMID- 3100160 TI - Radiologic diagnosis of early small gastric carcinoma and microgastric carcinoma. PMID- 3100161 TI - Catecholamine levels in spinal cord injuries. PMID- 3100162 TI - Two additional morphological characteristics for differentiating adult Wuchereria bancrofti and Brugia malayi. PMID- 3100163 TI - Systematic monitoring program in high risk pregnancies. A report of 100 cases. PMID- 3100164 TI - Prolonged pathologic pregnant uterus torsion. Report of a case. PMID- 3100165 TI - A simple technique for correction of cubitus varus. PMID- 3100166 TI - Computer analysis of the microvascular vasomotion. PMID- 3100168 TI - A case of giant hairy nevus on the eyelid area complicated by primary orbital schwannoma. PMID- 3100167 TI - H.I. CHU: pioneer clinical investigator of vitamin D deficiency and osteomalacia in China. A scientific and personal tribute. PMID- 3100169 TI - A case of mycetoma caused by Scopulariopsis maduromycosis. PMID- 3100170 TI - Experience in the microsurgical treatment of intracranial arteriovenous malformations. PMID- 3100171 TI - Reiter's disease with psoriasiform skin lesions. Report of 2 cases and a new method of differentiation. PMID- 3100172 TI - A permanent lead introduction technic: subclavian venipuncture and insertion of ventricular and/or atrial leads. PMID- 3100173 TI - Infection of legionella pneumophila. Report of 5 cases. PMID- 3100174 TI - Transitional cell carcinoma of urethra after treatment of urinary bladder cancer. PMID- 3100175 TI - A familial infection of giardiasis. PMID- 3100176 TI - Tritium beta-ray and 60CO gamma-ray caused dominant lethal mutation in mice. PMID- 3100178 TI - Differentiation of three developmental stages of bancroftian and malayian filariae in mosquito vectors. PMID- 3100177 TI - Variability in 24-hour urine sodium excretion in Chinese adults. PMID- 3100179 TI - A case report of achondroplasia. PMID- 3100180 TI - Papillary adenocarcinoma of the broad ligament. Report of a case and review of literature. PMID- 3100181 TI - Remission of acute lymphoblastic leukemia of childhood following acute infectious disease. A case report. PMID- 3100182 TI - Recent progress in the control of schistosomiasis in China. PMID- 3100183 TI - Recent development in research on tongue inspection. PMID- 3100184 TI - Protective effects of pentagastrin against stress-induced gastric lesions in rats. PMID- 3100186 TI - The histologic features and histogenesis of malignant ovarian Brenner tumor. PMID- 3100185 TI - Evaluation of genotoxic effect of epichlorohydrin on mice by micronucleus test. PMID- 3100188 TI - Nonspecific thyroiditis. PMID- 3100187 TI - Efficacy of single oral doses of praziquantel in treatment of schistosoma japonicum infection. PMID- 3100189 TI - Radiologic analysis of 540 normal Chinese sella turcica. PMID- 3100190 TI - Social epidemiology of aging in the United States. PMID- 3100191 TI - Optimizing filtration conditions and exposure selection for CT dual energy scanning. PMID- 3100192 TI - A case of fulminant systemic lupus erythematosus complicated by severe aspergillar septicemia confirmed by pathologic findings. PMID- 3100193 TI - Electron microscopic observation of epithelia in normal human esophagus. PMID- 3100194 TI - Acute traumatic diaphragmatic hernia. A report of 8 cases. PMID- 3100195 TI - Pyogenic infection of intervertebral discs in adults. PMID- 3100196 TI - Benefit of neonatal screening for phenylketouria. A report of the first case treated in China. PMID- 3100197 TI - Catgut heterograft for myringoplasty. Experimental study and clinical use. PMID- 3100198 TI - Appendectomy and cancer. An epidemiological evaluation. PMID- 3100201 TI - Clinical and fluorescein angiographic study of malignant melanoma of the choroid. PMID- 3100199 TI - Chromosome analyses of 2,319 cases in genetic counseling clinic. PMID- 3100200 TI - Genetic rules of primary angle-closure glaucoma. PMID- 3100203 TI - Myasthenia gravis. Laboratory and clinical analysis of 120 cases. PMID- 3100202 TI - Recurrence of immature ovarian teratoma in liver and lung. PMID- 3100205 TI - CT classification of hypertensive intracerebral hemorrhage for prediction of prognosis and selection of treatment. PMID- 3100204 TI - Acute respiratory infections in Beijing children. Epidemiological studies at Dongguan Brigade. PMID- 3100206 TI - A strain of Legionella pneumophila isolated from a pneumonic patient. PMID- 3100207 TI - Familial osteomalacia. Report of two families with various unusual features. PMID- 3100208 TI - Clinical nomenclature of echinococcosis based on 20 selected cases. PMID- 3100209 TI - Convoluted springy hemostatic scalp clip and its application in craniotomy. PMID- 3100211 TI - A case report of recurrence of primary subcutaneous meningioma in upper limb. PMID- 3100210 TI - Some anatomical data related to the transnaso-sphenoidal resection of pituitary fossa tumors. PMID- 3100212 TI - Long-term results of surgical treatment in 3,675 cases of esophageal carcinoma. PMID- 3100213 TI - Clinical study of 60 coronary angiography cases. PMID- 3100214 TI - Extracorporeal shock wave lithotripsy in the treatment of patients with renal stones. Report of 50 patients. PMID- 3100216 TI - Free toe transfer for thumb and finger reconstruction in 200 cases. PMID- 3100215 TI - General situation and features of geriatric epidemiological study in China. PMID- 3100217 TI - Studies on tetrandrine calcium antagonistic action. PMID- 3100218 TI - Observation of orbital ocular vascular architecture using plastic casts. PMID- 3100219 TI - Study of serum lipids and lipoproteins of healthy subjects in Shanghai. PMID- 3100221 TI - Low vision care and the elderly. PMID- 3100220 TI - Microcirculation in chronic viral hepatitis: clinical observation and treatment with traditional Chinese medicine. PMID- 3100222 TI - A preliminary investigation of endemic iodine goiter on the inclined plain in front of the Tianshan Mountains in Kuitun-Usum area. PMID- 3100223 TI - Early vascular grafting to prevent upper extremity necrosis after electrical burns: indications for surgery. PMID- 3100224 TI - Ganglioneuroblastoma of the middle ear: report of a case. PMID- 3100225 TI - Preliminary study on lung flukes from the Philippines with especial reference of some new findings. PMID- 3100226 TI - Myocardial preservation in China: a brief review and analysis. PMID- 3100227 TI - Acute respiratory infections in childhood in Beijing: An etiological study of pneumonia and bronchiolitis. PMID- 3100229 TI - In vitro cultivation of schistosoma japonicum from cercariae to egg-producing adult worms. PMID- 3100228 TI - Follow-up study on 250 patients with extra-intracranial arterial bypass operation for ischemic stroke. PMID- 3100230 TI - Glycerol test in Meniere's disease diagnosis. PMID- 3100232 TI - Staging in the treatment of maxillary sinus carcinoma. PMID- 3100231 TI - Coronary artery spasm: an analysis of 4 cases. PMID- 3100233 TI - Prosthodontic management of temporomandibular joint dysfunction syndrome: report of cases. PMID- 3100234 TI - Long-term results of surgical treatment of esophageal and cardial carcinoma: a report of 449 cases. PMID- 3100235 TI - Familial myasthenia gravis: report of 7 cases in 3 families. PMID- 3100236 TI - Neurological complications of Sjogren's syndrome: a report of two cases. PMID- 3100237 TI - Holt-Oram syndrome. PMID- 3100238 TI - Further study of five-drug combined chemotherapy for advanced breast cancer. PMID- 3100239 TI - Propagation of epidemic hemorrhagic fever virus in Meriones unguiculatus. PMID- 3100240 TI - Histopathology of paracancerous nasopharyngeal carcinoma in situ. PMID- 3100241 TI - [Diagnostic study of urinary tract infection]. PMID- 3100242 TI - [Evaluation of serological exclusion methods in diagnosing non-A, non-B hepatitis]. PMID- 3100243 TI - [Clinical application of the measurement of serum phenytoin sodium (DPH) concentrations]. PMID- 3100244 TI - [Strains of epidemic hemorrhagic fever virus isolated from the lungs of C. russula and A. squamipes]. PMID- 3100245 TI - [Culture and ultrastructural studies of human retinal pigment epithelium]. PMID- 3100246 TI - [Blood supply of the human optic chiasma]. PMID- 3100247 TI - [Analysis of 45 cases of re-operated retinal detachment]. PMID- 3100248 TI - [Diagnostic value of fundus angiography by oral administration of fluoresceins]. PMID- 3100249 TI - [Fundus changes in 280 middle-aged NIDDM patients]. PMID- 3100250 TI - [Serous detachment of the retinal pigment epithelium. Long-term follow-up studies]. PMID- 3100251 TI - [Ocular findings in systemic lupus erythematosus]. PMID- 3100252 TI - [Analysis of ocular fundus changes in post-hemorrhagic anemic patients]. PMID- 3100253 TI - [High myopia and primary open-angle glaucoma]. PMID- 3100254 TI - [Comparison of intubation dacryocystography and quantitative lacrimal scintillography]. PMID- 3100255 TI - [Branching of the central retinal artery in the Chinese]. PMID- 3100256 TI - [Further study on the decontaminated pretreatment of Mycobacterium tuberculosis cultures]. PMID- 3100257 TI - Fluorescence properties of allophycocyanin and a crosslinked allophycocyanin trimer. AB - Data on the wavelength and temperature dependence of both time-resolved and steady state fluorescence emission are presented for allophycocyanin (AP) and for a crosslinked allophycocyanin trimer (XL-AP) (Ong LJ and Glazer AN: Physiol Veg 23:777-787, 1985). AP dissociates at high dilution and is not stable above 40 degrees C even at moderate protein concentration. In contrast, XL-AP does not dissociate even at very low protein concentrations and is completely stable up to 60 degrees C in the presence of 0.75 M NaK-phosphate, pH 7.0. The results show that XL-AP is superior to AP for use in conjugates that absorb and emit in the red region of the spectrum. The high stability of XL-AP at elevated temperatures at high phosphate concentrations suggests that this derivative may be useful in conjunction with nucleic acid probes. PMID- 3100258 TI - Diabetic autonomic neuropathy: present insights and future prospects. PMID- 3100259 TI - Computerized dentistry. PMID- 3100260 TI - Image makeover. PMID- 3100261 TI - Parenteral nutrition in diabetes mellitus. PMID- 3100262 TI - [Meningoencephalitis due to Brucella abortus infection]. AB - A 45-year-old woman developed meningoencephalitis owing to an infection with Brucella abortus. The probable source of infection was contaminated ewe's milk cheese. Treatment with cefotaxim and doxycycline led to regression of the clinical symptoms and serological findings. PMID- 3100263 TI - [Possibilities of early diagnosis of intracranial meningioma based on clinical symptoms]. AB - In a retrospective study, 56 patients with intracranial meningiomas were investigated. The diagnosis was verified by computer tomography with subsequent selective cerebral angiography in all cases. At the time of admission, 62.5% of the patients had functional losses affecting the cranial nerves, 44% functional losses involving the long nerve tracts and 23.2% had cerebellar symptoms. Nonspecific clinical symptoms found comprised headaches in 61% of the patients; these were already present almost three and a half years before the final diagnosis. There was a marked organic psychological disorder in 50% of the patients which had already been present retrospectively for an average of 10 months. Cerebral convulsive attacks were present in 27% of the patients with partial convulsions (mainly of the "temporal lobe type") which had already been present for an average of 40 months before diagnosis; in the general tonic-clonic convulsions, the diagnosis was already made an average of six weeks after the first attack. These data show that nonspecific symptoms such as headaches, organic psychological disorders and cerebral convulsions may be early indicators for the presence of an intracranial space occupation and should be investigated further without delay. PMID- 3100264 TI - [Percutaneous endoscopy-controlled gastrostomy]. PMID- 3100265 TI - A comparison of cefadroxil and penicillin V in the treatment of streptococcal pharyngitis in children. AB - The efficacy of cefadroxil, an orally administered broad spectrum cephalosporin, was compared with that of penicillin V in several studies comprising more than 550 children with group A beta-haemolytic streptococcal (GABHS) pharyngitis. Both drugs alleviated clinical signs and symptoms and eradicated GABHS from the upper respiratory tract within 18 to 24 hours of the initiation of therapy. Approximately 8% of the patients treated with either cefadroxil or penicillin V had strains of GABHS isolated from 1 of their follow-up throat cultures which were identical to the strains isolated from their initial throat cultures, and were considered bacteriological treatment failures. Compliance was greater than 90% with all of the regimens used, but was significantly better with cefadroxil given as a 30 mg/kg dose once daily than with penicillin V given 3 times daily. There were no serious adverse reactions with either drug. Thus, cefadroxil was shown to be well tolerated and as effective as the standard agent, oral penicillin V, in the treatment of GABHS pharyngitis in children. PMID- 3100266 TI - Growth and proportionality in early childhood. III. Differences between babies of low birthweight in well-nourished and malnourished populations. AB - The growth patterns from birth to 7 yr of four groups of children are compared. They comprise: small-for-gestational age children in a highly favoured community born to (A) short mothers, (B) mothers of average height for their population; Guatemalan children living in a community where mild to moderate protein-calorie malnutrition was endemic. Data on a sample of children whose birthweights covered the normal range for gestational age were used as reference standards. At all ages and for almost all measures they were significantly larger than children in the other three groups. No differences were found between the boys in groups A and B; but girls in group A were lighter and shorter from 18 mth onwards. The Guatemalans were shorter and had smaller heads than group A from 12 mth onwards; and the boys were also lighter. No differences were found between the Guatemalans and group A for chest circumference in either sex from 2 yr onwards. Deficits in size at 4 yr of the Guatemalans compared with the Reference Sample ranged from 8.8% for stature, 6.8% head circumference, 5.9% weight, down to 3.9% for chest circumference. The differences between the four groups may broadly be taken to represent those due to low birthweight for gestational age, lower genetic potential, postnatal malnutrition, and their cumulative effects. Our findings offer a new perspective on their varying contributions to growth in size and shape during early childhood. PMID- 3100267 TI - [Effect of the postnatal induction of persistent estrus on the realization of the transplacental action of DMBA in 1st- and 2d-generation rats]. AB - In rats of the first generation subjected to transplacental DMBA action with subsequent (at the age of 3 months) induction of persistent estrus, the incidence of tumours significantly increased, particularly, those of the nervous system and the mammary gland. Rats of the second generation with induced persistent estrus and not exposed to DMBA developed neoplasms of the nervous system and kidneys which were not observed in the intact control animals. This fact suggests persistence of DMBA transplacental carcinogenic effect in a series of generations. PMID- 3100268 TI - [Scanning electron microscopic method for studying the interaction of normal peritoneal macrophages with tumor cells]. AB - It is shown that the damage action of normal peritoneal macrophages of mice includes inhibition of the proliferating activity of the mastocytoma P-815 cells and their complete destruction accompanied by the breaks of their cytoplasmic membrane. Scanning electron microscopy was used to reveal two types of contacts between peritoneal macrophages and cells P-815; the loss of microvilli and the appearance of blebs on cell surface in the case of adsorption of P-815 cells on macrophages; the contact through long filopodia which are sent forth by macrophages in the case when contacting cells are at some distance from each other. PMID- 3100269 TI - [Determination of the individual sensitivity of human stomach cancer cells to fluoropyrimidines by the cytomorphological criteria of heterotransplants in diffusion chambers]. AB - An optimal morphologic complex of parameters for evaluation of individual sensitivity of heterotransplants to two anti-cancer drugs--5-fluorouracil and ftorafur has been developed on the basis of clinical and experimental material and using 76 gastric malignant tumours, 1320 heterotransplants in diffusion chambers (DC) in vivo which were implanted to 660 animal recipients. A simplified preclinical evaluation method of the individual sensitivity of the human gastric tumour to fluoropyrimidines is recommended based on dynamic level of mitotic activity in DC in vivo heterotransplants. PMID- 3100270 TI - [Principles and significance of genetically-induced variability of the normal human EEG]. AB - This review describes the following results of human genetic research on the "normal" human EEG: As shown by comprehensive studies on mono- and dizygotic twins, interindividual variability of the human EEG under "normal" conditions is largely genetically determined. This was mainly shown for the resting EEG, but holds true also for the sleeping EEG, the reaction to ethanol, and for visually and auditory evoked potentials. Some fairly common EEG variants have been described which follow simple Mendelian modes of inheritance. Hence, they must go back to correspondingly simply differences in certain genes and gene-determined proteins. These variants have been useful as model systems for a neurobiologically founded research strategy in behaviour genetics of man. Comparative studies using psychological, neurophysiological (visual and auditory evoked potentials) and biochemical methods revealed group difference especially between carriers of the low-voltage EEG, the EEG with monomorphic alpha-waves and an EEG variant containing, in addition to alpha-waves, numerous diffuse beta waves. Utilizing concepts from basic research in neurophysiology, they could be explained by corresponding differences in central information processing. Individual differences of EEG reaction are also observed after a controlled ethanol load. They have a genetic basis, too. An especially clearcut reaction of the EEG to alcohol can be seen in individuals with irregular alpha-activity of low amplitude in the resting EEG. Moreover, these persons appear to be especially susceptible for "learning" to become alcohol addicts. Individual variability in maturation during childhood and youth of brain structures responsible for EEG production are also under genetic control. This EEG maturation influences intellectual and psychic maturation. PMID- 3100271 TI - [Cutaneo-muscular reflexes of the human hand. I. Methodologic principles]. AB - Cutaneo-muscular reflexes of the human hand were investigated with special regard to methodological characteristics. The reflexes were elicited by electrical stimulation of either the volar side of the index finger or the median nerve at the wrist, they were in both cases recorded from the abductor pollicis brevis muscle. Independent from the stimulus site, the reflex pattern consisted of four inhibitory and excitatory components (I1-E1-I2-E2): an H reflex was recorded from exclusively with median nerve stimulation. With increasing stimulus efficiency (stimulus strength or duration), the components I1, I2, and E2 were enhanced whereas the presumably transcortically mediated E1 component was successively attenuated. Systematic variation of the stimulus interval, in contrast, induced attenuation of I2 and slight enhancement of I1 only at short intervals (750 ms). Comparison of the reflex responses on both sides revealed a distinct asymmetry particularly of the amplitudes and--less distinct--of the latencies. Asymmetries of the E1 component should therefore be interpreted as pathologic only cautiously. PMID- 3100272 TI - [Cortical SEP of early and intermediate latency following stimulation of the median and tibial nerves in disseminated encephalomyelitis--relation to findings in cerebral nuclear magnetic resonance tomography]. AB - Cortical somatosensory evoked potentials following median and tibial nerve stimulation were compared with the findings in nuclear magnetic resonance imaging in 23 patients with multiple sclerosis, 11 of whom presented with their first disease manifestation. Pathological SEP's were found in 55 percent of patients presenting with first manifestation and in 83 percent of those with a longer duration of illness. Except for one patient with spinal cord involvement only, in whom no cerebral lesions were seen, all patients showed periventricular lesions in NMR. Between 1 and 16 (4.7 +/- 3.5) non-periventricular isolated lesions were found per patient. Cortical SEP's are affected differently by lesions within the thalamocortical system: Plaques within the internal capsule may result in SEP changes as seen in other causes of damage to this region. However, lesions in this strategic area may also remain clinically and electrophysiologically silent. Nevertheless, the size of the lesion seen in NMR is not relevant, as observed in one case of an extensive plaque within the centrum semiovale. Correlations between the lesions near the parietal cortex or within the parietal white matter and SEP-component alterations of intermediate latency (N55, N75) remained insignificant. PMID- 3100273 TI - [Effect of contact lenses and visual acuity on the registration of saccadic eye movements using an infrared reflection method]. AB - In order to examine the influence of contact lenses and visual acuity on recordings of saccadic eye movements with the infrared reflection method, horizontal 20 and 30 degrees saccades were recorded with and without contact lenses in 16 subjects (32 eyes) usually wearing contact lenses. As far as the main parameters of the saccades (accuracy, peak velocity and duration) were concerned, the reliability of the measurements (recognizable through the mean values) was not essentially influenced by the contact lenses. The precision of the measurements (recognizable through the standard deviation) was with the contact lenses significantly but, for clinical use, not essentially worse. The velocity waveforms of the saccades, however, were considerably changed by contact lenses in some cases. This is why examinations, in which saccadic velocity waveforms are used for diagnosis, should be performed without contact lenses. Visual acuity had no measurable influence on the main parameters of the saccades. However, considerably more corrective saccades were observed with contact lenses than without. There were reasons to believe that not the contact lenses themselves, but better visual acuity was responsible for the larger number of corrective saccades. PMID- 3100274 TI - Testicular LH receptors and circulating hormone levels in three mouse models for inherited diseases (Tfm/y, lit/lit and hyt/hyt). AB - In mice with testicular feminization (Tfm/y), the concentration of LH receptors (LH-R) in the testes was greatly elevated, when compared to their normal controls (Ta/y). The administration of hCG caused, 24 hours later, a much greater decrease in the number of testicular LH-R in Tfm/y than in Ta/y mice. However, whereas in Ta/y mice, the decrease in LH-R was accompanied by a greater than 20 fold increase in plasma testosterone (T) levels, the same dose of hCG failed to alter plasma T levels in Tfm/y mice. Tfm/y mice were also characterized by significantly elevated circulating LH, FSH and PRL levels. Administration of hCG decreased testicular LH-R concentration in little (lit/lit) mice, whereas it had no effect in hypothyroid (hyt/hyt) and normal mice. Treatment with hCG elevated plasma T levels in all animals, but this increase was smaller in lit/lit than in Lit/- mice, while being greater in hyt/hyt than in Hyt/- mice. The present results suggest that the Tfm locus in the mouse is involved in the regulation of testicular LH-R. The only effect of GH deficiency on the parameters studied is on hCG-stimulated testicular steroidogenesis. The lack of negative autoregulation of LH-R by hCG in hyt/hyt mice may indicate a more active testicular LH-R metabolism, perhaps as a consequence of the chronic elevation of plasma TSH levels. PMID- 3100275 TI - Effect of exogenous hormones on estrogen and progesterone release from cultured rat granulosa cells from various stages of estrous cycle. AB - Progesterone and estrogen levels in the culture media of granulosa cells isolated from rat ovarian follicles in all stages of estrous cycle were estimated using RIA, with special regard to hormone levels in proestrus. In control cultures the peak of progesterone release occurred at 20.00 h in proestrus. The addition of LH and FSH to the culture medium resulted in a remarkable stimulation of progesterone release by cells isolated in estrus. The highest concentration of estrogens in control cultures was observed in granulosa cells isolated at 18.00 h in proestrus. Exogenous LH and FSH stimulated the release of estrogen from the cells isolated on the days of estrus, metestrus and diestrus. Cultured granulosa cells maintained similar pattern of progesterone and estrogen release as the whole follicles did in vitro and in vivo. PMID- 3100276 TI - Pre- and postnatal developmental changes in hypothalamic content of rat growth hormone-releasing factor. AB - The ontogenesis of hypothalamic GH-releasing factor (GRF) in pre- and postnatal rats was examined by means of a specific rat GRF RIA. Whereas GRF content was undetectable (less than 10 pg/hypothalamus) on day 17 of gestation, it increased to 30-65 pg/hypothalamus during days 18-20. During postnatal life, hypothalamic GRF content increased more rapidly during days 20-50 than during days 0-20 or 50 90. GRF content was 900-1300 pg/hypothalamus in 50- to 90-day-old rats, and there was no consistent sex difference during postnatal life. Hypothalamic somatostatin levels, as measured by RIA, showed a developmental pattern similar to that of rat GRF. GRF immunoreactivity in hypothalamic extracts from fetal as well as adult rats exhibited HPLC retention times identical to that of synthetic rat GRF. Administration of antirat GRF serum produced a significant decrease in plasma GH levels in fetal rats on day 21 of gestation and in newborn pups 4 h after birth. Passive immunization against GRF caused a more marked suppression of plasma GH (75-85%) 6-9 h after birth and on postnatal day 3. The results demonstrate that immunoreactive GRF is present in measurable levels in the hypothalami of fetal and newborn rats, is chemically indistinguishable from synthetic rat GRF, and exhibits biological effects as early as day 21 of fetal life. PMID- 3100277 TI - Evidence for functional communication between folliculo-stellate cells and hormone-secreting cells in perifused anterior pituitary cell aggregates. AB - Dispersed anterior pituitary cells from adult female rats were separated by gradient sedimentation at unit gravity. The small-sized cell population on top of the gradient consisted of 65.6 +/- (SE) 4.2% (n = 8) cells immunoreactive to antiserum against S-100 protein, a marker of folliculo-stellate (FS) cells in rat pituitary. The corresponding fraction derived from adult male or immature female rats were also enriched in S-100 positive cells but to a lower extent. Only small numbers of S-100 positive cells were found in medium- and large-sized cell populations. Coaggregating the S-100 cell-enriched populations from adult females with other pituitary cell populations resulted in a clear-cut inhibition of the GH response to rat GH-releasing factor and beta-adrenergic agents, of the PRL response to TRH and angiotensin II (AII) and the LH response to LHRH. The magnitude of inhibition increased with the number of FS cells put into the coaggregates. In perifused aggregates prepared from different gradient fractions from immature females, there was a negative correlation between the occurrence of FS cells and the magnitude of the PRL response to AII. The low responsiveness to AII in FS cell enriched aggregates was not abolished when these aggregates were redissociated into single cells. It is suggested that FS cells constitute an intercellular messenger system for local inhibitory control of pituitary hormone secretion which is not based on direct and intimate contact between the interacting cells. PMID- 3100278 TI - Luteinizing hormone release from chicken pituitary cells: synergism between calcium and protein kinase C and its inhibition by calmodulin antagonists. AB - Continuous stimulation of cultured chicken pituitary cells with a native chicken hypothalamic GnRH, Gln8-GnRH, caused LH release, followed by rapid desensitization. Continuous exposure to calcium ionophore A23187 also produced a short-lived LH response, followed by desensitization. In contrast, continuous stimulation with a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), caused prolonged release of LH, reaching maximum amplitude after 1 h and slowly decreasing thereafter. Cells desensitized to GnRH remained fully responsive to A23187 and TPA, indicating that GnRH-mediated desensitization occurs at a level before protein kinase C activation and calcium mobilization. Simultaneous addition of A23187 and TPA resulted in a synergistic response which was independent of the order of addition of the two compounds. Synergism was also demonstrated between depolarizing concentrations of potassium and TPA and between veratridine and TPA, indicating that calcium entering via voltage-dependent channels also synergizes with phorbol ester. Despite the prolonged action of TPA, rapid pulsatile changes in LH release could be induced in cells treated with TPA and veratridine by rapidly changing the extracellular calcium concentration. This suggest that protein kinase C could function as an amplifier of the calcium signal generated by GnRH. Synergism between calcium and TPA was blocked by trifluoperazine, chlorpromazine, and W-7 [N-(6-aminohexyl)5-chloro-1 napthalenesulfonamide] at concentrations that had no effect on LH release mediated by TPA alone. This suggests that synergism is mediated via calmodulin and not a direct effect of calcium on protein kinase C. PMID- 3100279 TI - Prolactin modulates the gonadotropin response to the negative feedback effect of testosterone in immature male rats. AB - The effects of hyperprolactinemia (hyperPRL) and hypoprolactinemia (hypoPRL) on pituitary gonadotropin secretion and the feedback sensitivity to testosterone (T) were evaluated in immature male rats. At 34 days of age, rats were divided into three groups: group 1, controls, injected with oil; group 2, treated with bromocriptine mesylate (CB-154; 250 micrograms in oil/rat X day); and group 3, subjected to the transplantation of one pituitary from an adult female rat under the kidney capsule and treated with oil. The treatments were continued for 14 days. On day 8, each of these groups were further divided into three subgroups: intact, castrated, and castrated plus T treated. T treatment consisted of injection of T propionate (TP; 50 micrograms in oil/rat) on alternate days starting immediately after castration. Blood samples were obtained by cardiac puncture throughout the study. Plasma PRL levels were significantly reduced by CB 154 treatment and significantly increased by the pituitary graft (P less than 0.001). In intact immature male rats, hyper- or hypoPRL did not affect plasma LH levels, whereas hyperPRL reduced (P less than 0.01) plasma FSH concentrations. The postcastration increase in circulating LH levels was significantly increased (P less than 0.001) in rats treated with CB-154 24 h after castration. Moreover, the suppressive effects of TP on plasma LH and FSH levels were significantly (P less than 0.05) attenuated in hypoPRL rats. In pituitary-grafted rats, effects of castration and TP replacement on plasma LH levels did not differ from those in control rats. These results demonstrate that subnormal levels of PRL reduce the sensitivity of the hypothalamic-pituitary system to feedback inhibition by T. In contrast to previous findings in the adult rats, acute hyperPRL in immature male rats did not affect the negative feedback action of T on gonadotropin secretion. PMID- 3100280 TI - Effects of 5-hydroxytryptamine, dopamine, and aromatic L-amino acids on growth hormone (GH)-releasing factor-stimulated GH release in rat anterior pituitaries. AB - The importance of monoaminergic mechanisms for the regulation of GH-releasing factor (GRF)-stimulated GH secretion was studied in perifused rat anterior pituitaries. Dopamine (greater than 1 microL) reduced GRF-stimulated GH release, but 5-hydroxytryptamine (5-HT; 1 mL) had no effect. The substrates for L-aromatic amino acid decarboxylase, L-5-hydroxy-tryptophan(L-5-HTP; 10 microM) L dihydroxyphenylalanine; (1 mM), D,L-o-tyrosine (2 mM), and D,L-m-tyrosine (2 mM), all reduced GRF-stimulated GH release. Inhibition of the L-aromatic amino acid decarboxylase by benserazide (0.1 mM), carbidopa (0.1 mM), or alpha monofluoromethyldopa (0.1 mM) did not reduce the effect of the decarboxylase substrates on GH secretion. The enzyme inhibitors had no influence on hormone secretion per se. The findings indicate that dopamine may inhibit GRF-induced GH release at the pituitary level and that the precursor amino acids inhibit GH secretion independently of the formation of the corresponding amines. PMID- 3100281 TI - Hypothalamic factors differentially affect the proportions of cells that secrete growth hormone or prolactin. AB - Hypothalmic factors have been shown to regulate acutely the synthesis and release of adenohypophyseal hormones, yet few studies have investigated the long term effects of these agents on adenohypophyseal cell types. In the present study, we assessed the chronic influence of selected hypothalamic factors on the relative proportions of GH- and PRL-secreting cells in pituitary cultures derived from 5 day-old rats. Primary cultures were established and incubated for 6 days in the presence or absence of 0.1-microM doses of GH-releasing factor, LHRH, CRF, TRH, or vasoactive intestinal polypeptide and then subjected to reverse hemolytic plaque assays for analysis of the percentages of cells that released GH or PRL. In cultures from males, GH-releasing factor and LHRH treatment caused an increase in the proportion of PRL secretors and a commensurate decrease in the GH population. CRF increased PRL cells without affecting the GH secretors, while TRH reduced the percentages of both cell types, and vasoactive intestinal polypeptide had no effect. Virtually identical results were obtained for cells isolated from females. These results demonstrate that hypothalamic factors have the capacity to induce differential effects on the proportions of GH- and PRL-secreting cells. Surprisingly, our findings also show that hypothalamic factors that do not normally influence the acute release of GH or PRL can exert a chronic effect on the proportion of cells that secrete these hormones. PMID- 3100282 TI - Effect of estrogen on the growth hormone (GH) secretory response to GH-releasing factor in the castrate adult female rat in vivo. AB - Five groups (n = 11) of 250-g female rats were oophorectomized and immediately thereafter received daily sc injections of estradiol benzoate (EB; 0.05, 0.5, 5.0, and 50.0 micrograms) or vehicle for 28 days. A sixth group underwent sham operation and received injections of vehicle. Somatomedin-C (SmC) concentrations were determined before EB administration. After 4 weeks of EB treatment, the GH response to human GH-releasing factor (1-44) (GRF; 5 micrograms/kg, iv) was determined under pentobarbital anesthesia in seven animals from each group. Serum PRL, LH, and estradiol and plasma SmC concentrations were also measured. The GH secretory response to GRF (delta GH) was greatest in castrated animals receiving vehicle (P less than 0.05) and was significantly blunted in animals receiving 5.0 and 50.0 micrograms EB (P less than 0.05) compared to that in sham-operated animals. A significant negative correlation was observed between delta GH and serum PRL concentrations (r = -0.53; P less than 0.0001). SmC concentrations after treatment were significantly lower in animals receiving 5.0 and 50.0 micrograms EB (P less than 0.01), than in sham-operated animals and were elevated compared to those in sham-operated controls in the group receiving the lowest dose of EB (0.05 microgram; P less than 0.01). Posttreatment SmC levels correlated positively with delta GH (r = 0.58; P less than 0.001) and negatively with serum estradiol concentrations (r = -0.47; P less than 0.01). Pituitary glands from the remaining animals in each group (n = 4) were weighed and assayed for GH, PRL, and LH content. Pituitary PRL content increased with increasing doses of EB replacement and correlated strongly (r = 0.82; P less than 0.0001) with pituitary weight. In the castrated adult female rat, high doses of estrogen inhibited the GH secretory response to GRF in vivo and decreased SmC concentrations. Low dose estrogen increased SmC concentrations, although the GH secretary response to GRF in this group was similar to that in sham-operated rats. The latter observation suggests that the rise in SmC levels associated with low dose estrogen may not be mediated through a change in GH secretion. PMID- 3100283 TI - Effect of hypophysectomy on hypothalamic growth hormone-releasing factor content and release in the rat. AB - The possible regulation of hypothalamic GH-releasing factor (GRF) by GH was studied in untreated and GH-treated hypophysectomized rats by measurement of rat hypothalamic GRF content and release in vitro with a specific GRF RIA. Two weeks after hypophysectomy, animals not receiving hormone replacement showed a marked reduction in hypothalamic GRF content (to 28% of sham-operated control values; P less than 0.001). Replacement therapy with T4, cortisone, and testosterone for 9 days did not correct the decrease in hypothalamic GRF content in hypophysectomized rats, though the addition of GH therapy partially restored GRF levels (to 55% of control values; P less than 0.001). GRF release from incubated mediobasal hypothalamic fragments of hypophysectomized rats was decreased both basally and in response to 30 mM K+. This defect was completely corrected by prior GH treatment. The results suggest an impairment of GRF synthesis and release in the presence of GH deficiency. PMID- 3100284 TI - Hormonal control of epidermal growth factor receptors by gonadotropins during granulosa cell differentiation. AB - The hormonal induction of epidermal growth factor (EGF) receptor formation was analyzed during the maturation of granulosa cells obtained from diethylstilbestrol-implanted immature rats. In the absence of FSH, EGF receptors (as measured by the binding of [125I]iodo-EGF to the intact cells) rose by 50% at 6 h of culture, but then declined to about 25-40% of their initial levels at 24 96 h of culture. Scatchard analyses demonstrated the presence of high affinity EGF-binding sites in both freshly prepared cells and after FSH treatment. FSH stimulated a dose-dependent increase in the EGF receptor content of granulosa cells during a 96-h culture period. Concentrations of FSH as low as 2.5-5 ng/ml elevated EGF receptor levels 2- to 3-fold compared to those in untreated control cells, and 30 ng/ml FSH caused a maximal 15-fold rise. FSH increased EGF receptor levels approximately 2-fold in the first 6 h of culture and by up to 7-fold at 96 h compared to levels in freshly prepared cells. FSH treatment did not change the binding affinity (Kd = 5-6 X 10(-11) M) of the EGF receptor, but increased the total number of EGF-binding sites. The stimulatory effects of FSH on EGF receptor expression were mimicked by other cAMP-inducing ligands, including 8-bromo-cAMP, forskolin, and choleragen. Ligands known to inhibit granulosa cell function, including GnRH agonists and the phorbol ester 12-O-tetradecanoyl-phorbol 13 acetate, reduced the stimulation of EGF receptors by FSH. However, only 12-O tetradecanoyl-phorbol 13-acetate suppressed the induction of EGF receptors by 8 bromo-cAMP. In granulosa cells cultured for 48 h with FSH, subsequent treatment with hCG for 24 h reduced EGF receptor content by 25%. Autoradiographic studies with [125I]iodo-EGF in ovarian thin sections demonstrated that EGF-binding sites were uniformly dispersed throughout the ovaries of diethylstilbestrol-implanted rats. Treatment with PMSG markedly increased EGF receptors in the outer walls of the growing follicles, while hCG treatment after PMSG caused a general decline in ovarian labeling. These results indicate that FSH maintains and increases the number of EGF receptors during granulosa cell differentiation, while LH/hCG reduces EGF-binding sites. Such changes in EGF receptors in the presence of endogenous growth factors may influence the number and selection of follicles destined for ovulation. PMID- 3100285 TI - Norepinephrine and thyrotropin stimulation of iodide efflux in FRTL-5 thyroid cells involves metabolites of arachidonic acid and is associated with the iodination of thyroglobulin. AB - Ca2+-dependent and TSH-, norepinephrine (NE)-, and A23187-induced iodide (I-) efflux from FRTL-5 rat thyroid cells is inhibited by quinacrine and trifluoroperazine, agents that inhibit phospholipase A2 activity. Furthermore, I- efflux can be stimulated by an activator of phospholipase A2 activity, melittin. Phospholipase A2 action releases arachidonic acid from phospholipids; arachidonic acid enhances I- efflux in FRTL-5 cells. Inhibitors of arachidonic acid metabolism via the lipoxygenase pathway, 5,8,11,14-eicosatetraynoic acid and nordihydroguaiaretic acid, and via the cytochrome P450-linked epoxygenase pathway, piperonyl butoxide and 2-diethylaminoethyl-2,2-diphenyl valerate, but not an inhibitor of the cyclooxygenase pathway, indomethacin, can inhibit TSH-, NE-, and A23187-induced I- efflux. TSH, NE, and arachidonic acid stimulation of I efflux in FRTL-5 cells is associated with increased iodination of thyroglobulin, which is blocked by 10 microM 5,8,11,14-eicosatetraynoic acid and 50 microM piperonyl butoxide. The data thus suggest that TSH- and NE-induced I- efflux from FRTL-5 thyroid cells involves lipoxygenase and/or epoxygenase metabolites of arachidonic acid, released from phospholipids upon Ca2+-dependent activation of phospholipase A2. Since this process is associated with the iodination of thyroglobulin, TSH- and NE-induced I- efflux in FRTL-5 cells may represent the transport of I- from the cell into the follicular lumen in vivo. PMID- 3100286 TI - Functional variations among prolactin cells from different pituitary regions. AB - Reverse hemolytic plaque assays were used to compare the responsiveness of cells from different pituitary regions to the modulatory effects of human pancreatic GH releasing factor (GRF), TRH, and dopamine (DA). Tissues from the peripheral rim (outer zone) and the central region (inner zone) of adenohypophyses from day 10 lactating rats were dispersed with trypsin, and the cells were placed into culture. On the following day, these cells were subjected to GH plaque assays (conducted in the presence or absence of GRF) and PRL plaque assays (performed with or without TRH and DA). Cells from both zones responded similarly to GRF with a rapid acceleration of GH plaque formation. However, the rate of PRL plaque formation in response to TRH and DA differed between cells from these regions. For outer zone cells, plaque development increased greatly with TRH treatment, but was only moderately affected by DA. Plaque formation from inner zone cells was influenced slightly by TRH, but markedly inhibited by DA. These results suggest that PRL, but not GH, cells from these pituitary regions are differentially responsive to at least two hypothalamic secretagogues. We then performed fixed sequential plaque assays to determine whether the proportions of cells that released PRL only (classical mammotropes) or those that released both GH and PRL (mammosomatotropes) also differed between the inner and outer zones. Using this approach, we found that the outer zone contained a much larger proportion of dual hormone secretors than did the inner zone. These results, when taken together with the responsiveness differences discussed above, raise the possibility that the release of PRL from mammotropes and mammosomatotropes is regulated differently and that the ratio of these two cell types may dictate, in part, the manner in which a specific region of the pituitary responds to hypothalamic input. PMID- 3100287 TI - Thyrotropin-releasing hormone and histidyl-proline diketopiperazine: stimulation of secretion from hypothalamic fragments in vitro by depolarizing agents. AB - The influence of depolarizing agents on the release of TRH and histidyl-proline diketopiperazine [C(HP)] from rat hypothalami was examined in vitro. Thin hypothalamic fragments from two separate animals were incubated in Krebs-Ringer bicarbonate media. Immunoreactive TRH and C(HP) released into medium were determined by specific RIAs. Potassium and ouabain, a Na+/K+-ATPase inhibitor, stimulated TRH and C(HP) secretion in a graded fashion, but the magnitudes of C(HP) secretory responses were less than those of TRH. The stimulation by KCl and ouabain was inhibited by the addition of verapamil, a Ca2+ channel blocker, or omission of Ca2+ from medium in the presence of EGTA. Veratridine, a Na+ channel activator, also stimulated TRH and C(HP) release from rat hypothalami, and this stimulation was completely blocked by tetrodotoxin, a Na+ channel blocker. The results of this study indicate that TRH and C(HP) release from rat hypothalami are stimulated by membrane depolarization in vitro and depend on Na+ and Ca2+ influx. PMID- 3100288 TI - Changes in testicular inhibin after a single episode of heating of rat testes. AB - Brief heating (43 C for 15 min) of the scrota of adult rats was used to induce reversible spermatogenic damage to the testes. In these animals the changes in testicular inhibin content and an index of inhibin production rate, measured after efferent duct ligation, were examined and correlated with serum gonadotropin levels. The effect of heating was not evident until after 1 week when testis weight, inhibin content, and inhibin production rate were significantly reduced and both serum FSH and LH were elevated. By 2 weeks, the maximal effects were observed, and, thereafter, all parameters gradually returned to control values (FSH: by 6 weeks; testis and epididymal weight, inhibin content, inhibin production rate, and seminiferous tubule fluid production: by 17 weeks). Throughout the study, serum testosterone levels showed no significant changes. Significant inverse correlations were found between serum FSH levels and inhibin content (r = -0.502, P less than 0.001) or inhibin production rate (r = 0.533, P less than 0.001), and these were taken as supportive evidence for the hypothesis that inhibin is involved in the feedback control of pituitary FSH secretion. Although serum LH levels were also negatively correlated to the corresponding inhibin content (r = -0.669, P less than 0.001) or inhibin production rate (r = -0.420, P less than 0.001), recent findings of Leydig cell dysfunction in these animals led us to relate the transient rise in LH to the altered state of Leydig cell function. PMID- 3100289 TI - Pulpal reactions to glutaraldehyde and paraformaldehyde pulpotomy dressings in monkey primary teeth. PMID- 3100290 TI - Bonding of enamel-dentin crown fractures with GLUMA and resin. PMID- 3100291 TI - Synopsis of the first International Conference on Antimutagenesis and Anticarcinogenesis: mechanisms. PMID- 3100292 TI - Modulation by thyroxine of the amount of lactase protein in the jejunum of adult rats. AB - Adult rats starved for 48 h received a daily injection of thyroxine over a 3-day period before they were killed. When compared to nourished animals, starvation provoked a 4- to 5-fold increase in immunoreactive lactase protein, which paralleled a similar stimulation of lactase activity in the brush border membranes of the proximal jejunum. Exogenous thyroxine completely inhibited the starvation-induced increase in immunoreactive lactase protein in both the intracellular and the brush border membranes. PMID- 3100293 TI - Induction of meningeal inflammation by diverse bacterial cell walls. PMID- 3100294 TI - Decreased sensitivity of Neisseria gonorrhoeae to quinolone compounds. PMID- 3100295 TI - The regulation of adenylate cyclase by guanine nucleotides in Dictyostelium discoideum membranes. AB - Extracellular cAMP induces the activation of adenylate cyclase in Dictyostelium discoideum cells. Conditions for both stimulation and inhibition of adenylate cyclase by guanine nucleotides in membranes are reported. Stimulation and inhibition were induced by GTP and non-hydrolysable guanosine triphosphates. GDP and non-hydrolysable guanosine diphosphates were antagonists. Stimulation was maximally twofold, required a cytosolic factor and was observed only at temperatures below 10 degrees C. An agonist of the cAMP-receptor-activated basal and GTP-stimulated adenylate cyclase 1.3-fold. Adenylate cyclase in mutant N7 could not be activated by cAMP in vivo; in vitro adenylate cyclase was activated by guanine nucleotides in the presence of the cytosolic factor of wild-type but of not mutant cells. Preincubation of membranes under phosphorylation conditions has been shown to alter the interaction between cAMP receptor and G protein [Van Haastert (1986) J. Biol. Chem. in the press]. These phosphorylation conditions converted stimulation to inhibition of adenylate cyclase by guanine nucleotides. Inhibition was maximally 30% and was not affected by the cytosolic factor involved in stimulation. In membranes obtained from cells that were treated with pertussis toxin, adenylate cyclase stimulation by guanine nucleotides was as in control cells, whereas inhibition by guanine nucleotides was lost. When cells were desensitized by exposure to cAMP agonists for 15 min, and adenylate cyclase was measured in isolated membranes, stimulation by guanine nucleotides was lost while inhibition was retained. These results suggest that Dictyostelium discoideum adenylate cyclase may be regulated by Gs-like and Gi-like activities, and that the action of Gs but not Gi is lost during desensitization in vivo and by phosphorylation conditions in vitro. PMID- 3100296 TI - Stimulation of arachidonic acid metabolism via phospholipase A2 by triethyl lead. AB - Human blood platelet aggregation and the formation of icosanoids were studied in response to triethyl lead chloride (Et3PbCl). Concentrations higher than 75 microM stimulate platelets to aggregate, whereas low concentrations (less than or equal to 20 microM) caused platelet hypersensitivity to aggregating agents such as collagen or arachidonic acid. Incubation of suspensions of washed platelets with Et3PbCl resulted in a stimulated liberation and subsequent metabolism of arachidonic acid. This response was dependent on the concentration of Et3PbCl and the incubation time. Using low concentrations of Et3PbCl and up to 3 h of incubation, the lipoxygenase product 12-hydroxy-5,8,10,14-icosatetraenoic acid was the major metabolite. Under normal conditions, however, stimulation of platelets with collagen, thrombin, or arachidonic acid leads to higher amounts of the cyclooxygenase products 12-hydroxy-5,8,10-heptadecatrienoic acid and thromboxane B2. The aggregation of human platelets induced by Et3PbCl was inhibited by three different drugs: acetylsalicylic acid, forskolin and quinacrine; but only quinacrine could prevent the liberation of arachidonic acid and the appearance of its metabolites. These specific effects of the inhibitors on Et3PbCl-stimulated platelets as well as the differences in the pattern of arachidonic acid metabolites and phosphatidic acid suggest a direct stimulatory action of Et3PbCl on platelet phospholipase A2. PMID- 3100297 TI - Transcranial Doppler CO2 test for the detection of hemodynamically critical carotid artery stenoses and occlusions. AB - Cerebral CO2-reactivity was tested by transcranial Doppler sonography (Doppler CO2 test) in 232 patients. Time averaged flow velocity in the middle cerebral artery at the 40 mm Hg blood pCO2 level was taken as a reference point, and the relative increase of flow in hypercapnia of 46.5 mm Hg pCO2 was defined as "Normalized Autoregulatory Response" (NAR). A total of 82 patients with no evidence of cerebrovascular disease gave "normal" values for NAR (23.2 +/- 5.2 SD). In 150 patients with 233 stenoses and occlusions of the internal carotid artery NAR was significantly decreased in higher-grade stenoses (P = 0.01 for 80% diameter reduction, P less than 10(-6) for 90% or more). In such stenoses, patients with NAR less than 14 had suffered more frequently (P less than 0.01) from ipsilateral transient ischemic attacks and/or stroke during the previous 6 months than patients with "normal" NAR. Preoperative NAR less than 14 always improved to "normal" values following carotid surgery, while preoperative NAR greater than 19 remained unchanged (60 cases). The transcranial Doppler CO2 test is thought to be a reliable noninvasive method to detect hemodynamically critical carotid stenoses and occlusions. This may be of interest in selecting patients for superficial temporal artery-middle cerebral artery bypass and carotid surgery. For practical use 4 categories of NAR are suggested. PMID- 3100298 TI - A study of the structural heterogeneity of low-density lipoproteins in two patients homozygous for familial hypercholesterolaemia, one of phenotype E2/2. AB - The structural heterogeneity of the low-density lipoproteins (d 1.019-1.063 g ml 1) in two female patients homozygous for familial hypercholesterolaemia, one of phenotype E2/2, has been evaluated using a new ultracentrifugal density gradient procedure. The mass distribution, chemical composition, particle size and heterogeneity, hydrated density and apolipoprotein content of 16 LDL subfractions were determined. By gradient gel electrophoresis, the lighter LDL subfractions (d 1.016-1.037 g ml-1) displayed a single particle species which progressively diminished in size from 24.8 to 22.0 nm with increase in density. By contrast, subfractions of higher density (d greater than 1.037 g ml-1) exhibited two LDL particle species of distinct size; one component decreased in size from 21.8 to 20.4 nm with increase in density, while the second maintained an essentially constant diameter (between 22.5 and 23.5 nm) across these LDL subfractions. Immunoblotting with anti-apo-B100 of LDL subspecies separated by gradient gel electrophoresis showed all particles to contain apo-B100. However, dot-blots and immunoblotting with a monoclonal antibody to lipoprotein (a) (Lp(a)) revealed that the LDL particle subspecies of greatest diameter (22.5-23.5 nm) present in the denser subfractions (d greater than 1.037 g ml-1) also contained the Lp(a) antigen. These findings, taken together with the high plasma Lp(a) levels (greater than 60 mg dl-1) in our patients, raise the possibility that Lp(a) may contribute in a significant manner to the atherogenic process in homozygous familial hypercholesterolaemia. PMID- 3100299 TI - Lymphocyte response to Klebsiella in ankylosing spondylitis. AB - The lymphocyte response of mononuclear cells (MNC) to Klebsiella (Klebs) was studied in ankylosing spondylitis (ASP) and, for comparison, in patients convalescing from Klebs infection and in HLA-B27+ and B27- healthy blood donors. When large doses of various Klebs cell envelope structures were used, MNC from all healthy blood donors were stimulated to produce LIF but not to synthesize significant amounts of DNA. In contrast, MNC from convalescent patients showed LIF synthesis (but no significant proliferation) even when small doses of the Klebs biostructures were used. This heightened LIF response to Klebs was long standing and could be demonstrated even after serum antibodies had vanished. Very similarly, MNC from ASP patients did not proliferate significantly, but could be activated to produce LIF even with small doses of Klebs. The heightened LIF response to Klebs in ASP appeared to be correlated with the clinical activity and/or duration of the disease. In contrast, there was no correlation between the presence of HLA-B27 in ASP patients or healthy controls and the LIF or proliferative response to Klebs. PMID- 3100300 TI - Trans- and paracellular calcium transport across the colonic mucosa after short- and long-term treatment with 1,25-dihydroxyvitamin D3. AB - The electrical parameters and the unidirectional fluxes of 45Ca and 3H-mannitol were measured in preparations of rat colon descendens freed from the muscularis externa and mounted in a modified Ussing-chamber. Two criteria were used to differentiate between changes in the trans- and the paracellular calcium transport after treatment with 1,25(OH)2D3: the fluxes of the simultaneously measured 3H-mannitol as a paracellular marker; the 45Ca fluxes in preparations with clamped potentials. After a short-time (6 h) pretreatment by s.c. administration of 1,25(OH)2D3 (250 ng kg-1) in normal rats the mucosa (m) to serosa (s) 45Ca flux under short circuit conditions increased about 65%, whereas the electrical parameters and the 3H-mannitol fluxes remained unchanged. In clamped epithelia the PD-independent m to s 45Ca flux was increased, whereas the PD-dependent flux remained unchanged. In contrast, after long-time (4 days) induction by 1,25(OH)2D3 the m to s 45Ca flux increased under short circuit conditions by about 100% and the m to s 3H-mannitol flux increased by 50%, PD and Isc decreased by more than 60%, whereas tissue resistance was the same, in clamped epithelia the calculated PD-independent, transcellular m to s 45Ca flux was 2.4 times and the PD-dependent, paracellular 45Ca-flux was 1.9 times higher than in controls, whereas the s to m 45Ca flux remained unchanged. On the basis of the relevant references the following conclusions were drawn: after short-time exposure to 1,25(OH)2D3 only the PD-dependent, transcellular m to s calcium transport is increased; this is probably due to a liponomic effect of 1,25(OH)2D3 at the brush border membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100301 TI - Fibronectin replacement in patients with fulminant hepatic failure. AB - Patients with fulminant hepatic failure have low levels of the plasma opsonizing protein fibronectin together with cardiovascular disturbances similar to those in septic shock where microembolization of capillary beds by particulate debris has been proposed to lead to multi-organ failure. Six patients with fulminant hepatic failure received a bolus injection of a concentrated fibronectin-rich preparation. The mean plasma immunoreactive fibronectin level increased from 53 +/- SE 12 micrograms ml-1 initially to 295 +/- 30 micrograms ml-1 (P less than 0.001) at 1 h after fibronectin administration. The in vitro plasma opsonic activity was also increased from 5.6 +/- 3.6% of control to 102 +/- 13% (P less than 0.005) at 1 h. No similar effect was observed with the clearance of microaggregated albumin, but as its clearance is probably not dependent on fibronectin it may reflect a different aspect of reticuloendothelial cell function. No significant changes were observed in cardiopulmonary function or oxygen utilization and it is possible this is because clearance of opsonized particles is limited by damage to Kupffer cells. PMID- 3100303 TI - Human biliary beta-glucuronidase: correlation of its activity with deconjugation of bilirubin in the bile. AB - Total and conjugated bilirubin contents of gall-bladder and hepatic biles before and after 24-h incubation at 37 degrees C and beta-glucuronidase activity of hepatic biles were determined in forty-eight patients divided equally into four groups: no stones or control (C), cholesterol stones (CS), black pigment stones (black PS), and brown pigment stones (brown PS). The percent conjugation of bilirubin is lower in gall-bladder biles and hepatic biles after incubation, particularly in black PS and brown PS, when compared with hepatic biles before incubation. Mean endogenous beta-glucuronidase activities at pH 5.2 were 12.0, 15.5, 44.5 and 147.7 nmol min-1 ml-1 for C, CS, black PS, and Brown PS, respectively, which correlated well with the degree of deconjugation of bilirubin in gall-bladder and hepatic biles and with the rate of deconjugation of hepatic bile incubated at 37 degrees C. Only four biles in brown PS exhibited bacterial enzyme activity. We concluded that though bacterial beta-glucuronidase might be responsible for deconjugation of bilirubin in some patients in brown PS, endogenous biliary beta-glucuronidase could play a key role in the pathogenesis of pigment cholelithiasis. PMID- 3100302 TI - Osteoporosis with hip fracture: changes in calcium regulating hormones. AB - It has been suggested that there are two distinct types of involutional osteoporosis in women. Loss of ovarian function causes spine and wrist fractures in middle-aged women whilst a decline in renal endocrine function and bone formation is responsible for fractures, especially of the hip, in elderly women. We have investigated calcium regulation in post-menopausal women with hip fractures in their seventh decade together with non-osteoporotic controls of similar age. The major findings were reduced secretion of calcitonin (P less than 0.01) and 1,25 dihydroxy-vitamin D (P less than 0.025) in the osteoporotics as compared with controls. No differences in plasma levels of calcium, parathyroid hormone and 25 hydroxyvitamin D were observed. Our results show some similarities with those reported in both proposed types of osteoporosis, suggesting considerable overlap between them. Secondary hyperparathyroidism does not appear to be a usual feature of osteoporotic women with hip fracture up to age 75 years. Our hormonal findings are more in keeping with marked oestrogen deficiency, suggesting that loss of ovarian function is a major determinant of the osteoporosis in these women. PMID- 3100304 TI - Effects of Legionella pneumophila sonicate on human neutrophil granulocyte and monocyte chemotaxis. AB - The interaction of L. pneumophila serogroup 1 sonic extract with human polymorphonuclear neutrophils and monocytes was studied in an in vitro chemotaxis assay. The sonicate showed heat-stable chemotactic activity towards neutrophils and monocytes. It also exhibited cytotoxicity for neutrophils but not for monocytes. Incubation and pretreatment with the sonicate at apparently non-toxic concentration resulted in inhibition of the chemotactic response of neutrophils to various chemoattractants while monocyte chemotaxis was unaffected. The inhibitory activity was reduced to one half by heat treatment of the sonicate. High endotoxic activity was demonstrated in both heated and non-heated extract. Only two antigens (nos 1 and 61) were identified in the sonicate exposed to 121 degrees C for 1 h. It is therefore suggested that the lipopolysaccharide (no. 61) of L. pneumophila could contribute to the chemotactic activity. The adverse effects exerted by L. pneumophila on neutrophils may be one of the mechanisms by which Legionella bacteria resist the normal phagocytic host defenses. PMID- 3100305 TI - Hepatic regeneration and metabolism after partial hepatectomy in normal rats: effects of insulin therapy. AB - The effect of insulin therapy on liver regeneration has been studied in normal fed rats 12, 24 and 48 h after partial hepatectomy. Dry weight of regenerating liver increased between 12 and 48 h after partial hepatectomy and was unaffected by insulin therapy. [6-3H] Thymidine uptake peaked at 24-h (24.7 +/- 2.4% of total liver cells) and insulin treatment had no additional effect. At 12-h after partial hepatectomy, hepatic [ATP] was decreased 15%, while [ADP] and [AMP] were increased 47% and 83% respectively compared with sham-operated animals. Partial hepatectomy also caused an increase in hepatic [triglyceride], a decrease in hepatic [glycogen] and an increase in the levels of glucose and several glycolytic intermediates. The hepatic redox ratios, [lactate]:[pyruvate] and [3 hydroxybutyrate]:[acetoacetate], were elevated. Insulin therapy had only minor effects on hepatic adenine nucleotide levels, intermediary metabolite concentrations or intrahepatic redox ratios after partial hepatectomy. These findings suggest a decreased hepatic intracellular energy state in regenerating liver; insulin therapy in normal rats does not influence this metabolic change nor the regenerative response. PMID- 3100306 TI - Hepatic regeneration and metabolism after partial hepatectomy in diabetic rats: effects of insulin therapy. AB - The effect of insulin deficiency on liver regeneration has been assessed in untreated v. insulin-treated streptozotocin (65 mg kg-1) diabetic rats, 12, 24 and 48 h after partial hepatectomy. Dry weight of regenerating liver increased from 12 to 48 h after partial hepatectomy and insulin treatment caused a further minor increase at 24 h. [6-3H]Thymidine uptake in untreated rats peaked at 24 h (12.5 +/- 3.4% of total cells labelled). Insulin therapy produced a delayed 168% rise in uptake at 48 h. Insulin deficiency alone in sham-operated animals caused a 33% decrease in hepatic [ATP], while [ADP] rose by 43% and [AMP] by 86% at 12 h. Partial hepatectomy produced only minor further abnormalities in untreated animals. Insulin therapy increased hepatic [ATP] and decreased [ADP] and [AMP] 12 h after partial hepatectomy, but [ATP] remained decreased (15%) and [ADP] and [AMP] increased (45% and 73% respectively) compared with insulin-treated sham operated controls. Metabolite changes observed after partial hepatectomy in untreated animals, including a decrease in hepatic [glycogen] and increases in [triglyceride] and the ratios of [lactate]:[pyruvate] and [3 hydroxybutyrate]:[acetoacetate], were partially reversed by insulin treatment. Insulin deficiency thus impairs regeneration after partial hepatectomy and magnifies the decline in hepatic intracellular energy state and the metabolite changes associated with liver regrowth. PMID- 3100307 TI - Combined treatment with cholestyramine and nicotinic acid in heterozygous familial hypercholesterolaemia: effects on biliary lipid composition. AB - In ten patients with heterozygous familial hypercholesterolaemia, combination therapy with cholestyramine and nicotinic acid was instituted for a minimum of 2 months. During therapy, plasma low-density lipoprotein levels were reduced by 32%, and low-density lipoprotein to high-density lipoprotein ratios by 40%. The cholesterol saturation of fasting gall-bladder bile was reduced by 33% during treatment. We conclude that long-term combination therapy with cholestyramine and nicotinic acid is practically feasible in heterozygous familial hypercholesterolaemia, normalizes plasma cholesterol and low-density lipoprotein levels in many patients, and does not result in unwanted side-effects on biliary lipids. It should therefore be considered as the therapy of choice in this condition. PMID- 3100308 TI - Simulation of the metabolism and enterohepatic circulation of endogenous chenodeoxycholic acid in man using a physiological pharmacokinetic model. AB - The metabolism and enterohepatic circulation of chenodeoxycholic acid (CDC), a major primary bile acid in man, has been stimulated using a multicompartmental physiological pharmacokinetic model which was previously reported and used to simulate the metabolism of cholic acid. The model features compartments and linear transfer coefficients. Compartments, which are defined as the pools of single chemical species in well defined anatomical volumes, are aggregated into nine 'spaces' based on anatomical and physiological considerations (liver, gall bladder, bile ducts, duodeno-jejunum, ileum, colon, portal blood, sinusoidal blood, and general circulation). Each space contains several compartments which correspond to the compounds present in that space, for example, the compound in question and its biotransformation products. For CDC (as for cholic acid in the previous simulation) each space contains three compartments corresponding to the unconjugated bile acid, its glycine amidate, and its taurine amidate. Transfer coefficients, which denote the fractional amount of the compartment's contents exiting per unit time, are categorized according to function: flow, for example gall-bladder contraction (which involves transfer of all substances contained in the space at the same fractional rate); biotransformation (which transfers the substrate from one compartment to another within the same space); or transport (which denotes movements between contiguous compartments, belonging to different spaces across a diffusion membrane or a cellular barrier). The model is made time dependent by incorporating meals which trigger gall-bladder emptying and modify intestinal flow. The transfer coefficients in the cholic acid model were modified for the CDC model since there is indirect evidence that CDC amidates (probably chenodeoxycholylglycine) are absorbed from the duodeno-jejunum and the first pass hepatic clearance of CDC species differs from that of cholyl species. The model was then used with all existing experimental data to simulate CDC metabolism in healthy humans over a 24-h period during which three meals were ingested. Satisfactory agreement was obtained between simulated and experimental data indicating that this model continues to be useful for describing the metabolism of bile acids and may also be of value for describing the metabolism of drugs whose metabolism is similar to that of bile acids. PMID- 3100309 TI - Ciclosporin and prednisone v. prednisone in treatment of Graves' ophthalmopathy: a controlled, randomized and prospective study. AB - Forty patients with Graves' ophthalmopathy stages III-V were divided into two groups in a random manner according to their year of birth. Group I received prednisone in decreasing dosage. Group II received prednisone at a comparable dosage and ciclosporin. Steroids were discontinued after 10 weeks in the two groups. In the patients of group II, ciclosporin was continued over 12 months. The therapeutic effect was assessed by an activity score based on subjective and objective symptoms (computerized tomography and sonography of the orbit, Hertel values, clinical findings). All signs of endocrine ophthalmopathy improved significantly in both groups (P less than 0.01 in group I; P less than 0.001 in group II). The improvement was significantly greater in group II (P less than 0.05) according to the predefined score. After corticosteroids were discontinued, inflammatory signs recurred in nine patients in group I and in one of group II. During the observation period of 12 months, relapses occurred in eight out of twenty patients in group I and in only one out of twenty in group II. Muscle thickness decreased in nine patients in group II, 6 months after beginning therapy. At this time, the results were not influenced in any of the twenty patients in group I. Microsomal antibodies decreased significantly (P less than 0.001) in the ciclosporin group, whereas no change was seen in the other group. Renal values rose within the normal range in group II. In this group, an infection with Klebsiella pneumoniae occurred in one patient after 4 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100310 TI - Pulmonary extraction of circulating noradrenaline in man. AB - Pulmonary plasma kinetics of endogenous noradrenaline (NA) and tritium labelled L noradrenaline (3H-NA) was studied in fifteen subjects during pulmonary arterial catheterization. Plasma NA concentration in femoral artery ranged from 0.5 to 8.2 nmol l-1, mean 2.3 nmol l-1, which was not significantly different from that of age-matched control subjects. The lungs extracted both endogenous NA and 3H-NA significantly, but no significant pulmonary extraction of endogenous adrenaline was found. The pulmonary arterial-systemic arterial extraction ratio of NA was mean 0.08 (n = 9) as compared to that of 3H-NA: mean 0.07 (n = 8, NS). Likewise mean pulmonary clearances of NA and 3H-NA were not significantly different (97 ml min-1 X M-2 v. 124 ml min-1 X M-2, NS). Estimated whole-body clearance of noradrenaline was mean 0.80 l min-1 X M-2 (n = 6) while the pulmonary clearance amounted to 19% of this value. The small, but significant, pulmonary extraction of circulating noradrenaline implies that whole-body clearance, as estimated from infusion rate and systemic arterial sampling, will be overestimated by approximately 7%. As pulmonary extraction of NA and 3H-NA was almost identical, the results indicate no significant pulmonary contribution to circulating noradrenaline. PMID- 3100311 TI - Gastrointestinal absorption of aluminium from single doses of aluminium containing antacids in man. AB - Ten subjects with normal renal function were given different single doses of aluminium containing antacids (1, 4, or 8 tablets). The antacid tablets (aluminium content 244 mg tablet-1) were chewed and swallowed either with water, with orange juice, or with citric acid solution. There was a marked increase in serum concentration of aluminium when the antacids was ingested with citric acid (P less than 0.001) or with orange juice (P less than 0.05). When antacids were taken with water, a slight, but significant increase in serum aluminium concentration was seen with 4, but not with 1 or with 8 tablets. Following all doses of antacid, a significant increase in 24 h urinary excretion of aluminium was seen. The estimated absorption of aluminium was 8 and 50 times higher when antacids were taken with orange juice or with citric acid, respectively, than when taken with water. Thus, measurable quantities of aluminium are absorbed from single oral doses of antacids. The absorption is substantially enhanced by concomitant ingestion of citric acid. PMID- 3100312 TI - Etidronate disodium for treating hypercalcaemia of malignancy: a double blind, placebo-controlled study. AB - The efficacy of intravenous etidronate disodium in controlling hypercalcaemia of malignancy was evaluated in a double blind, placebo-controlled study. Twenty patients with known malignant disease and hypercalcaemia were randomly assigned on a 2:1 basis to etidronate 7.5 mg kg-1 body weight or placebo for 3-5 days. All patients received 3000 ml saline and 40 mg furosemide per day. Eighteen patients completed the study. Eleven of twelve in the etidronate group reached normocalcaemia compared to two of six in the placebo group (P = 0.05). The etidronate group showed a greater decrease in serum calcium than the placebo group (P less than 0.02). The renal calcium excretion decreased significantly in the etidronate group, but not in the placebo group. A slight increase in serum creatinine was observed in the etidronate group compared to placebo on the first day of treatment. The difference however disappeared the following days. Intravenous etidronate treatment in combination with rehydration and furosemide constitutes a safe and efficient alternative in the treatment of hypercalcaemia of malignancy, although a first approach always should be rehydration. PMID- 3100313 TI - Pharmacokinetics of oral glycerol-1-nitrate. AB - The plasma kinetics and urinary excretion of glycerol-1-nitrate (G-1-N), a water soluble metabolite of glycerol trinitrate with anti-anginal potential, have been investigated in healthy human volunteers following oral doses of 10, 20 and 40 mg tablets and 20 mg as drops. In all volunteers G-1-N was rapidly absorbed. The mean concentration-time curves peaked 40 min after administration of tablets at 144 ng/ml (10 mg), 308 ng/ml (20 mg) and 573 ng/ml (40 mg). After the drops the peak of 324 ng/ml occurred at 1 h. The areas under the G-1-N concentration-time curve and the G-1-N peak heights were linear with dose. Tablets and drops can be regarded as bioequivalent with respect to area under the curve and elimination half-life. The bioavailability of the 20 mg tablet relative to the 20 mg drops was 98.6% in terms of area under the curve. The mean apparent half-life of G-1-N elimination from plasma was 2.69 +/- 0.67 h (n = 46). The mean residence time of G-1-N in the body was 4.65 h compared to 0.28 h for glycerol trinitrate after buccal administration. Female volunteers were found to have significantly lower areas under the curve than male volunteers. The difference was probably due to differences in body weight. Renal excretion does not play an important role in the elimination of oral G-1-N from the body. An overall average of 5.42% of the G 1-N dose was excreted in the urine; free drug accounted for 4.02% and conjugated drug for 1.40%. PMID- 3100314 TI - Correlations between in vitro dissolution, in vivo bioavailability and hypoglycaemic effect of oral glibenclamide. AB - A study has been carried out investigating four different marketed oral preparations of glibenclamide, correlating the effectiveness of the drug in these preparations in lowering plasma glucose concentrations with the in vitro dissolution of the drug, measured by the British Pharmacopoeal and Desaga methods, and the in vivo bioavailability, assessed in 12 healthy human volunteers. The two dissolution methods yielded different rank orders of ease of dissolution of the drug from the various preparations; the findings of neither dissolution method correlated adequately with the results of the in vivo bioavailability studies, which correctly predicted the abilities of the preparations to reduce plasma glucose concentrations. Relative to an oral glibenclamide solution the bioavailabilities of the drug from three tablet preparations were 0.69, 0.49 and 0.24. The mean elimination half-life of the drug was 1.5 h and assuming complete bioavailability of the drug from oral solution the mean systemic clearance was 0.095 l kg-1h-1, and the mean apparent volume of distribution was 0.20 l kg-1. It is concluded that it may be unsafe to use in vitro dissolution data as a basis for assessing the bioequivalences of different glibenclamide preparations intended for oral use. PMID- 3100315 TI - Excretion of gold into human breast milk. AB - After the administration of 70 mg and 50 mg aurothiomalate, respectively, to 2 patients with rheumatoid arthritis, significant amounts of gold appeared in breast milk. PMID- 3100316 TI - Genetic markers in the blood of three species of tamarins (Saguinus mystax, S. labiatus and S. oedipus). AB - Alkaline phosphatase (Alp), esterase-I (Es-I), esterase-II (Es-II), carbonic anhydrase (CA), cell esterase (cEs), esterase-D (Es-D), isocitrate dehydrogenase (ICD), malate dehydrogenase (MDH), 6-phosphogluconate dehydrogenase (PGD), tetrazolium oxidase (To), ceruloplasmin (Cp), Haptoglobin (Hp) and hemoglobin (Hb) in 58-75 samples of three species of tamarins (Saguinus mystax, S. labiatus and S. oedipus) were detected by means of horizontal starch gel electrophoresis. Two types (Es-I 1 and Es-I 2) for Es-I, four types (Es-II 1, Es-II 2, Es-II 3 and Es-II 2-3) for Es-II, three types (cEs 1, cEs 2 and cEs 1-2) for cEs, three types (PGD 1, PGD 2 and PGD 1-2) for PGD, two types (To 1 and To 2) for To, and three types (Hp 3, Hp 1-3 and Hp 2-3) for Hp were observed. However, Alp, CA, Es-D, ICD, MDH, Cp and Hb were monomorphic. In the S. mystax, no Es-II or PGD variants were observed. No Es-II variant was seen in the S. oedipus. Gene frequencies of cEs, PGD and Hb were biased in the three species. It is concluded that six polymorphic loci are useful as genetic markers for a species or individual. PMID- 3100317 TI - Turnover of sulfated glycosaminoglycans in fibroblasts derived from patients with Werner's syndrome. AB - Fibroblasts derived from patients with Werner's syndrome (WS) were incubated with radioactive sulfate to study the incorporation of 35S into glycosaminoglycans (GAGs). The accumulation of cell-associated 35S radioactivity in the GAGs of WS fibroblasts was consistently higher than parallel accumulation in normal human fibroblasts, but was substantially less than in fibroblasts derived from patients with Hurler's syndrome (HS). However, when fibroblasts were labeled with 35SO4(2 ), trypsinized to remove extracellular and pericellular radioactive GAGs, replated, and chased to follow the fate of the intracellular radioactivity, both WS and normal cells showed a rapid release of the intracellular 35S, while HS cells showed little or no loss of intracellular radioactivity. The radioactivity released from WS and normal cells was of low molecular weight (LMW), eluting from gel filtration columns at the same position as free sulfate. These results establish that WS cells degrade intracellular sulfated GAGs and argue against the hypothesis that a defect in GAG degradation pathways is the basis for the increased level of cell-associated GAGs. Other possible explanations for the increased cell-associated [35S]GAGs in WS cells as compared with normal cells were also considered: increased GAG sulfation; an increase in GAG chain length; an increased rate of GAG synthesis; and a decreased rate of shedding of cell surface proteoglycan into the medium. No difference between normal and WS fibroblasts in any of the above parameters was observed. These results strongly imply that the primary biochemical defect in WS fibroblasts does not involve sulfated GAG metabolism. PMID- 3100318 TI - Association of vinculin to the platelet cytoskeleton during thrombin-induced aggregation. AB - Vinculin is a protein generally believed to be involved in membrane-cytoskeleton interaction, and its presence in platelets has been verified earlier. Here we show that in resting bovine platelets, vinculin is not associated with the Triton insoluble cytoskeletal fraction but becomes incorporated into it during the thrombin-induced activation process. The incorporation starts around the same time as the release reaction and only after the shape change and the first phase of aggregation have taken place. Its time course parallels the cytoskeletal association of actin and certain other contractile proteins. Vinculin is a minor component of platelet cytoskeleton and only about 10% of the total platelet vinculin becomes incorporated into the Triton X-100 residue. PMID- 3100320 TI - Embryonic substantia nigra grafts innervate embryonic striatal co-grafts in preference to mature host striatum. AB - Embryonic substantia nigra grafts partially reinnervate the dopamine-denervated corpus striatum when implanted adjacent to that structure. This reinnervation is generally limited to a small portion of the denervated striatum and does not completely compensate for the behavioral effects of a 6-hydroxydopamine lesion of the substantia nigra. This limited reinnervation may be due to the fact that adult denervated striatum is not an ideal target for dopaminergic neurites. To test this hypothesis, embryonic striatum and embryonic substantia nigra were implanted together into the lateral ventricle of adult rats, adjacent to the denervated striatum. Five months after transplantation, fluorescence histochemistry showed that the embryonic striatal grafts were exclusively reinnervated with little or no reinnervation of the adult host striatum. When substantia nigra was implanted without embryonic striatal co-grafts, reinnervation of the host striatum was observed. We conclude that embryonic striatum is a better target tissue than adult denervated striatum for developing dopaminergic neurites and hypothesize that this difference may be due to the presence or the absence of specific trophic factors. PMID- 3100319 TI - Apolipoprotein E synthesis in neurofibrosarcoma and schwannoma cell cultures from two individuals with neurofibromatosis. AB - Apolipoprotein E is expressed in neurofibrosarcoma and Schwannoma cell cultures derived from two patients with different types of neurofibromatosis, but not in six cell cultures derived from the benign neurofibromatosis neurofibromas. In addition, a cell culture derived from a nonneurofibromatosis human malignant astrocytoma showed apolipoprotein E expression. Although all cells in either the neurofibrosarcoma or Schwannoma cultures appeared morphologically similar (suggesting homogeneity), apolipoprotein E was immunochemically detected in the perinuclear region of only half of the cells. Thus, production of apolipoprotein E in neurofibromatosis-associated neurofibroma tumors may be a marker for a specific subclass of transformed cells. The expression of apolipoprotein E in glial cell neoplasms is possibly related to an alteration in their lipid metabolism. PMID- 3100321 TI - Schistosoma mansoni: migration potential of normal and radiation attenuated parasites in naive guinea pigs. AB - Compressed tissue autoradiography using [75Se]selenomethionine labelled parasites has been used to investigate the migration potential of normal and radiation attenuated cercariae of Schistosoma mansoni in naive guinea pigs. By Day 14 after infection. 44% of normal parasites were detected as reduced silver foci in the liver; this value corresponded well with the number of liver parasites recovered by retrograde perfusion of the hepatic portal system on Day 42 (42% of the challenge). In contrast, cercariae subjected to 50 krad of gamma irradiation failed to migrate out of the skin. The migration capacity of 20 krad irradiated parasites was less severely affected in that about half of the challenge parasites reached the lungs, but virtually none moved to the liver. These data are discussed in relation to the kinetics of immunity induced in guinea pigs by infection or vaccination with normal or radiation attenuated parasites. PMID- 3100322 TI - Integrated epidemiological system for acute viral hepatitis in Italy (SEIEVA): description and preliminary results. AB - An integrated epidemiological system for the surveillance of acute viral hepatitis SEIEVA which linked notifications to available serology results and used a standard risk factor questionnaire is described. Results of over 1300 cases reported by 35 participating local health units (USL's) during the first 18 months of the programme are presented. Overall the annual reported incidence of acute viral hepatitis was 70 per 100,000. There were marked regional and age specific differences in the incidence of each type of viral hepatitis. The annual incidence per 100,000 of hepatitis A in southern children was 133 while in northern young adults the incidence of hepatitis B was 88 and hepatitis non-A non B was 43. The possible roles of shellfish consumption in the transmission of non A non-B hepatitis at all ages were highlighted. PMID- 3100323 TI - Medicaid expenditures for maternity and newborn care in America. AB - An Alan Guttmacher Institute (AGI) survey of the Medicaid programs in each state and the District of Columbia found that some 542,000 low-income women have a Medicaid-subsidized delivery each year--about 15 percent of all women who give birth. The proportion ranges from three percent in Alaska to 25 percent in Michigan. The federal and state governments spend almost $1.2 billion annually for maternity care (including prenatal, postpartum and newborn care); the average expenditure per patient is $2,200. Tennessee reports the highest expenditure per patient ($3,500) and Louisiana the lowest ($1,300). Only the highest payments under Medicaid are close to charges for maternity care in the open market, a fact that results in a significant disincentive for physicians and hospitals to accept Medicaid patients. The $1.2 billion spent for Medicaid-subsidized maternity care compares with an estimated $11.5 billion spent for such care nationwide. Thus, Medicaid pays for about 10 percent of the nation's maternity care bill, although Medicaid subsidizes deliveries for 15 percent of all women who give birth. The figures for maternity care do not include Medicaid expenditures for neonatal intensive care, which, for the 17 states reporting data, average about $11,800 per infant. Although only about six percent of all newborns whose deliveries are subsidized by Medicaid require neonatal intensive care, such care is so expensive that it adds about 30 percent to all Medicaid expenditures for maternity care. Increased Medicaid payments for maternity care, including prenatal care, could have a positive impact on health outcomes for low-income mothers and their babies, and could reduce the necessity for massive and expensive medical treatment for newborns. PMID- 3100324 TI - Public benefits and costs of government funding for abortion. AB - In state referenda to end public funding of abortions for poor women, one of the most successful tactics of abortion foes has been to charge that abortion funding increases the burden on taxpayers. A state-by-state analysis by The Alan Guttmacher Institute (AGI) shows that the opposite is the case. For every tax dollar spent to pay for abortions for poor women, about four dollars is saved in public medical and welfare expenditures. The savings are in public expenditures that otherwise would have to be incurred because of the babies that poor women would have borne. On the basis of earlier research, it was assumed that 20 percent of Medicaid-eligible women who could not obtain abortions would give birth. Public costs examined in the AGI analysis include Medicaid expenditures for prenatal care, delivery and postnatal care for the mother, and for newborn care, neonatal intensive care and pediatric care for the child for the first two years of life; as well as expenditures for Aid to Families with Dependent Children (AFDC), food stamps and the Special Supplemental Food Program for Women, Infants and Children (WIC) during those first two years. The benefit-to-cost ratio varies from about 9:1 in Massachusetts to 2:1 in Hawaii and Pennsylvania. The net savings for the nation as a whole over a two-year period if abortions were publicly funded in every state would total at least $339.6 million. PMID- 3100325 TI - Large scale, rapid purification of recombinant tissue-type plasminogen activator. AB - Recombinant tissue-type plasminogen activator (rt-PA) from cultures of a genetically manipulated Bowes melanoma cell line (TRBM6) was purified in batches of average volume 451 using an autoclavable, reusable, continuous chromatography system comprising zinc chelate-Sepharose CL4B and lysine-Sepharose CL4B. After eight successive purifications the rt-PA was ultrafiltered to yield a preparation containing 4.9 mg protein/ml and 2.7 X 10(6) IU/ml. Analysis by SDS polyacrylamide gel electrophoresis followed by staining with Coomassie brilliant blue R250 showed major protein bands at Mr = 63,000 and 65,000; most of the material was in the 1-chain form. The potential usefulness of a simple, rapid continuous chromatography system that can be operated under aseptic conditions is discussed. PMID- 3100326 TI - The formation of plasma membrane blebs in hepatocytes exposed to agents that increase cytosolic Ca2+ is mediated by the activation of a non-lysosomal proteolytic system. AB - Exposure of isolated hepatocytes to extracellular ATP, cystamine or ionophore A23187 was associated with an increase in cytosolic Ca2+ concentration, a stimulation of intracellular proteolysis, and the appearance of plasma membrane blebs which preceded the loss of cell viability. Both bleb formation and cell killing were prevented when inhibitors of Ca2+-activated neutral proteases, such as antipain or leupeptin, were included in the incubation medium, whereas inhibitors of lysosomal proteases had no effect. Thus, the activation of a Ca2+ dependent, non-lysosomal proteolytic system appears to be responsible for the plasma membrane blebbing and, ultimately, the cytotoxicity associated with treatment of hepatocytes with agents that disrupt intracellular Ca2+ homeostasis. PMID- 3100327 TI - A calorimetric study of Ca2+ binding by the parvalbumin of the toad (Bufo): distinguishable binding sites in the molecule. AB - Microcalorimetric titrations of the major isotype of parvalbumin (tPA) from toad (Bufo) skeletal muscle, with Ca2+ in the presence and absence of Mg2+ and with Mg2+ in the absence of Ca2+, have been carried out at 25 degrees C and pH 7.0. The results indicate that the two binding sites in each molecule are distinguishable from each other for both Ca2+ binding and Mg2+ binding. Such a characteristic is distinctly different from those of other parvalbumins. The enthalpy changes determined are distinctly different from those of bullfrog parvalbumins on Ca2+ or Mg2+ binding, but are similar to those on Mg2+-Ca2+ exchange. The results indicate that the reaction of Mg2+-Ca2+ exchange is driven almost entirely by the large favorable enthalpy change. PMID- 3100328 TI - Chemical synthesis and expression in E. coli of a human Val8-calcitonin gene by fusion to a synthetic human interferon-gamma gene. AB - A gene coding for human Val8-calcitonin (Val8-hCT) was synthesized by the solid phase phosphite approach and fused to a synthetic human immune interferon-gamma (IFN-gamma) gene. The IFN gene was previously shown to be expressed at a very high level in E. coli [(1986) Gene, in press] due to the control of a strong synthetic promoter and strong ribosome binding site. The cells harboring the fused gene produced 100-150 micrograms per l of bacterial suspension of immunoreactive calcitonin in the form of hybrid IFN-gamma-Val8-hCT protein consisting of 140 amino acids. The Val8-hCT can be released from this protein by CNBr treatment. PMID- 3100329 TI - Inositol phospholipids are probably not the source of arachidonic acid for eicosanoid synthesis in astrocytes. AB - In astrocyte-enriched cultures of the rat cerebral cortex the Ca2+ ionophore A23187 provoked the breakdown of inositol phospholipids, the liberation of arachidonic acid and the release of prostaglandins E2, F2 alpha, I2 and thromboxane A2. However, agonists for receptors also coupled to inositol phospholipid metabolism in these cells failed to produce an increase in the release of both arachidonic acid and eicosanoids. Results suggest that the A23187 stimulated release of arachidonic acid and eicosanoids is caused by a phospholipase A2-mediated attack on lipids other than the inositol phospholipids. Moreover, receptors linked to inositol lipid turnover are not involved in the control of eicosanoid release from astrocytes. PMID- 3100330 TI - Human Gi protein alpha-subunit: deduction of amino acid structure from a cloned cDNA. AB - The amino acid sequence of the alpha-subunit of Gi, the human adenylate cyclase inhibiting GTP-binding protein, has been deduced from the nucleotide sequence of a DNA clone complementary to Gi alpha mRNA from differentiated U937 cells. The cDNA encodes a polypeptide of 355 amino acids (Mr 40456). The amino acid sequence homology between human Gi alpha and rat, murine, and bovine Gi alpha is 98.6, 97.7 and 87.9% respectively. Differentiation of the U937 cells from monoblasts to monocyte-like cells resulted in a 3-fold increase in Gi alpha mRNA as well as a 3.6-fold increase in the 41 kDa pertussis toxin substrate presumed to be Gi alpha. Thus, increased levels of this G-protein are associated with monocyte differentiation and appear to be regulated transcriptionally. PMID- 3100331 TI - Direct evidence for the participation of pyruvate in N-hydroxylation of lysine. AB - The contribution of pyruvate to the formation of N6-acetyl-N6-hydroxylysine by a cell-free system of Aerobacter aerogenes 62-1 involved in the production of the dihydroxamate siderophore, aerobactin, has been assessed by a study of the influence of its analogs as well as of inhibitors of thiamine pyrophosphate dependent decarboxylation reactions. These studies have provided unequivocal evidence for pyruvate functioning not only as a source of reducing equivalents in the initial step of N-hydroxylation of lysine but also as a precursor of the acetyl moiety in the subsequent conversion of the N-hydroxy amino to its N6 acetyl derivative. PMID- 3100332 TI - Sequence identity between a lysine-containing peptide from Leuconostoc mesenteroides glucose-6-phosphate dehydrogenase and an active site peptide from human erythrocyte glucose-6-phosphate dehydrogenase. AB - Peptides recently isolated and sequenced from a bacterial (Leuconostoc mesenteroides) glucose-6-phosphate dehydrogenase are remarkably homologous to an active site region of the human erythrocyte enzyme, although the enzymes differ in their overall amino acid composition and kinetic properties. The computer program ALIGN, used to determine the best alignment between the two enzyme sequences, gives match-scores which are statistically highly significant. PMID- 3100333 TI - Clostridium botulinum type C produces a novel ADP-ribosyltransferase distinct from botulinum C2 toxin. AB - The culture medium of certain strains of Clostridium botulinum type C contains two separable ADP-ribosyltransferases. Besides the ADP-ribosylation of actin due to botulinum C2 I toxin, a second microbial enzyme causes the mono-ADP ribosylation of a eukaryotic protein with a molecular mass of about 20 kDa found in platelets, neuroblastoma X glioma hybrid cells, S49 lymphoma cells, chick embryo fibroblasts and sperm. The eukaryotic substrate is inactivated by heating and trypsin treatment. In contrast, the novel ADP-ribosyltransferase, which can be separated by DEAE-Sephadex chromatography, is largely resistant in the short term to trypsin digestion. PMID- 3100334 TI - The azurin gene from Pseudomonas aeruginosa codes for a pre-protein with a signal peptide. Cloning and sequencing of the azurin gene. AB - The azurin gene from Pseudomonas aeruginosa is located on a 1.3 kb long PstI DNA fragment. Its nucleotide sequence has been determined. It appears that the gene codes for a pre-protein with a 19 amino acid long signal sequence which possibly assists in the transport of the azurin over the periplasmic membrane. PMID- 3100335 TI - Induction of cyclo-oxygenase by interleukin-1 in rheumatoid synovial cells. AB - The ability of interleukin-1 (IL-1) to stimulate prostaglandin E2 (PGE2) production by human rheumatoid adherent synovial cells was found to be time dependent and sensitive to protein synthesis inhibitors. Cells incubated with exogenous arachidonic acid (10 microM) showed no increase in PGE2 production. However, with IL-1 (2.5 U/ml) and exogenous arachidonic acid there was a marked increase, with levels reaching twice that for cells incubated with IL-1 alone. Aspirin pre-treatment studies and the use of [acetyl-14C]aspirin showed that IL-1 increased PGE2 production through the induction of cyclo-oxygenase. PMID- 3100336 TI - Pertussis toxin inhibits the angiotensin II and serotonin-induced rise of free cytoplasmic calcium in cultured smooth muscle cells from rat aorta. AB - Angiotensin II, serotonin and K+-depolarization cause an increase in free cytoplasmic Ca2+ in cultured smooth muscle cells. The involvement of a guanine nucleotide-binding protein has been investigated by using pertussis toxin. When smooth muscle cells were pretreated with pertussis toxin angiotensin II and serotonin-induced rise of cytosolic Ca2+ was found to be significantly reduced whereas the Ca2+ influx mediated by K+-depolarization remained unchanged. These results suggest the participation of a guanine nucleotide-binding protein in the receptor-mediated rise of intracellular Ca2+. PMID- 3100337 TI - Catalytic activities of synthetic octadeoxyribonucleotides as coenzymes of poly(ADP-ribose) polymerase and the identification of a new enzyme inhibitory site. AB - The catalytic activity of highly purified poly(ADP-ribose) polymerase was determined at constant NAD+ concentration and varying concentrations of sDNA or synthetic octadeoxyribonucleotides of differing composition. The coenzymic activities of deoxyribonucleotides were compared in two ways: graphic presentation of the activation of poly(ADP-ribose) polymerase in the presence of a large concentration range of deoxyribonucleotides and by calculating kD values for the deoxyribonucleotides. As determined by method i, auto-mono-ADP ribosylation of the enzyme protein at 25 nM NAD+ was maximally activated at 1:1 octamer/enzyme molar ratios by the octadeoxyribonucleotide derived from the regulatory region of SV40 DNA (duplex C). At a 0.4:1 sDNA/enzyme ratio, sDNA was the most active coenzyme for mono-ADP-ribosylation. At 200 microM NAD+, resulting in polymer synthesis and with histones as secondary polymer acceptors, duplex C was the most active coenzyme, and the octamer containing the steroid hormone receptor binding consensus sequence of DNA was a close second, whereas sDNA exhibited an anomalous biphasic kinetics. sDNA was effective on mono-ADP ribosylation at a concentration 150-200 -times lower than on polymer formation. When comparison of deoxyribonucleotides was based on method ii (kD values), by far the most efficiently binding coenzyme for both mono and polymer synthesis was sDNA, followed by duplex C, with (dA-dT)8 exhibiting the weakest binding. The synthetic molecule 6-amino-1,2-benzopyrone (6-aminocoumarin) competitively inhibited the coenzymic function of synthetic octadeoxyribonucleotides at constant concentration of NAD+, identifying a new inhibitory site of poly(ADP ribose) polymerase. PMID- 3100338 TI - Pathways to chronic inflammation in rheumatoid synovitis. AB - Postcapillary venules resembling the high endothelial venules (HEVs) of lymphoid tissues have often been observed at sites of chronic inflammation. We have therefore postulated that such venules may be an important site of lymphocyte migration into rheumatoid synovial membrane and that inflammatory cell products may act on endothelial cells (ECs) to increase lymphocyte emigration. Electron microscopic examination of rheumatoid synovial membranes showed that a strong correlation existed between the proportion of lymphocytes in perivascular tissue and the height/base ratio of the ECs in those areas. In addition, binding experiments showed that peripheral blood mononuclear cells preferentially bound to ECs in sections of rheumatoid synovial membrane that had the morphological appearance of HEVs. In vitro binding experiments, in which lymphocyte adhesion to human umbilical vein EC monolayers was measured, showed that adhesion was enhanced by preincubation of the ECs with interferon-gamma or interleukin 1 (IL 1). The central role of IL 1 in increasing lymphocyte migration into the rheumatoid synovial membrane was also supported by the findings that IL 1 is chemotactic for lymphocytes, ECs can secrete IL 1, and IL 1 activity is readily detectable in synovial fluids of rheumatoid arthritis patients. PMID- 3100339 TI - Pathway to carrageenan-induced inflammation in the hind limb of the rat. AB - A sequential 43-step pathway scheme for the inflammatory response of the rat to interdermal injection of carrageenan (C) was devised. It consisted of a nonphagocytic inflammatory response (NPIR) followed by a phagocytic inflammatory response (PIR) in the dermis and an epidermal NPIR. The dermal NPIR comprised edema, hyperemia, and hyperalgesia followed by hypoalgesia. Antiserotonin agents inhibited the hypoalgesia and part of the edema. These findings and histological observations suggested that dermal mast cells were injured by C. The hyperalgesia and part of the edema were sensitive to arachidonate cyclooxygenase inhibitors (AACOIs). It is speculated that injured mast cells metabolize arachidonic acid and reactive intermediates, not prostaglandins, mediate the NPIR hyperalgesia and part of the edema. The dermal PIR consisted of mobilization of neutrophils, edema, hyperalgesia, mobilization of monocytes, and proliferation of fibroblasts and vascular tissue. Selective drug actions revealed that the edema, hyperalgesia, and monocyte mobilization of the PIR depended on the mobilization of neutrophils. After the mobilization of neutrophils, AACOIs reduced edema formation and hyperalgesia. Arachidonic acid metabolism by neutrophils is speculated to produce the mediators of phagocytic inflammatory (PI) edema and hyperalgesia. Monocyte function was associated with cessation of PI edema formation and phagocytosis of neutrophils and cellular debris. Interleukin 1 is speculated to mediate the adherence of neutrophils to injured dermal endothelium. The epidermal NPIR consisted of edema, hyperplasia, and hyperkeratosis. These parameters were not studied mechanistically. There was no evidence for histamine, bradykinin, platelets, clotting factors, or complement mediating any events in the pathway. PMID- 3100340 TI - Thromboxane A2 biosynthesis in human disease. AB - Thromboxane A2 (TxA2), the predominant cyclooxygenase product of human platelets, is a potent vasoconstrictor and platelet agonist. Although its biological properties are readily appreciable in vitro, it has been difficult to define its biological importance in vivo. To a large extent this reflected the problems associated with efforts to monitor biosynthesis of this eicosanoid and the lack of selective pharmacological probes that prevented the synthesis of TxA2 or antagonized its biological action in vivo. Recently the analysis of urinary metabolites of TxB2 has become simplified so that the methodology is readily applicable to clinical studies. This provides a noninvasive, time-integrated index of Tx biosynthesis. Although one cannot definitively establish a tissue of origin for metabolites measured in urine, indirect evidence suggests that urinary TxB2 derives primarily from the kidney whereas its dinor metabolite predominantly reflects platelet biosynthesis under physiological conditions. Although plasma concentrations of TxB2 are readily confounded by platelet activation ex vivo, the enzymatic metabolites formed from TxB2 have recently been identified and appear to bypass this problem. Combined analysis of long-lived (e.g., 11-dehydro-TxB2) and short-lived (e.g., 2,3-dinor-TxB2) metabolites in plasma promise to more accurately localize phasic increases in the biosynthesis of TxA2 and have been paralleled by the development of antagonists of the TxA2/prostaglandin endoperoxide receptor and their study of humans. The use of such specific probes in conditions characterized by abnormal biosynthesis of TxA2 promises to define the biological role of this mediator for humans. PMID- 3100341 TI - Eicosanoid production by the coronary microvascular endothelium. AB - Cultured rabbit coronary microvessel endothelial (RCME) cells have been used as an in vitro model to study the regulation of microvascular endothelial cell prostaglandin (PG) production by hormones, vasoactive drugs, and inflammatory mediators in an environment that can be tightly controlled and that is unaffected by interactions with other cell types, physical stimulation, or alterations in oxygenation. The most potent stimuli for RCME cell PG secretion were substances associated with inflammation, including histamine, interleukin 1, leukotriene D4, fMet-Leu-Phe, interferon-gamma, and exogenous phospholipases. Inhibition of calcium availability by lower [Ca2+]o or by treatment with calcium channel blockers reduced A23187-stimulated PG release but increased PG synthesis from exogenous arachidonic acid (AA). These observations suggest that Ca2+ may regulate several steps in the pathway leading to PG synthesis and release. Elevated intracellular [Ca2+] may, on the one hand, promote PG production by stimulating phospholipase A2 leading to AA release and, on the other hand, limit the magnitude of the response by increasing the rate of AA reacylation. Glucocorticoids reduce PG production by RCME cells via an action that requires new protein and mRNA synthesis and appears to involve the production of an endothelial cell-derived phospholipase inhibitory protein, or "endocortin." Thus, microvascular endothelial cells can both contribute to (by the release of PGs and possibly platelet-activating factor-acether) and limit (by the production of endocortins) the degree of a local inflammatory response in the heart. PMID- 3100342 TI - Endothelium, arachidonic acid, and coronary vascular tone. AB - Vasoactive mediators play an important role in the control of coronary vascular tone. Arachidonic acid (AA) metabolites and endothelium-derived vasoactive factors have been implicated in coronary vasoregulation. AA can be metabolized via three separate routes in blood vessels, mediated by cyclooxygenase, lipoxygenase, and cytochrome P-450-dependent monooxygenase enzymes. AA can evoke endothelium-dependent relaxations that are due in part to the formation of cytochrome P-450-dependent metabolites, inasmuch as drugs that modify cytochrome P-450 activity produce parallel changes in endothelium-dependent relaxations to AA. Moreover, some cytochrome P-450-derived metabolites formed biologically cause relaxations of isolated blood vessels. A cytochrome P-450-dependent pathway does not appear to contribute to endothelium-dependent relaxations induced by acetylcholine, which suggests that there may be a number of endothelium-derived relaxing factors (EDRFs). In addition, two endothelium-derived contractile factors have been described, including an unidentified cyclooxygenase metabolite of AA and a polypeptide isolated from cultured cells. As both prostaglandin I2 and acetylcholine-induced EDRF also inhibit platelet aggregation, endothelial injury and loss of these factors may predispose to vasospasm precipitated by release of platelet-derived mediators such as thromboxane A2 (TXA2) and 5 hydroxytryptamine. Unstable angina may be a clinical syndrome in which these events occur, which can be alleviated by inhibition of platelet activation and TXA2 formation with aspirin. Attenuation of endothelium-dependent relaxations can also occur without loss of endothelial cells. Neutrophil-endothelium interactions, precipitated by an ischemic episode, may initiate endothelial dysfunction and underlie the development of vasospasm in some conditions. Whether increased production of endothelium-derived contractile factors also occurs in vasospastic conditions remains to be determined. PMID- 3100343 TI - Antagonism by methysergide of neurogenic vasoconstriction in the dog forelimb. AB - In the flow-regulated dog forelimb, electrical stimulation of the efferent median nerve produced frequency-dependent increases in perfusion pressure. These vasoconstrictor effects were attenuated by a large dose of phentolamine, an alpha 1 and alpha 2 blocking drug. Administration of methysergide after phentolamine completely reversed the vasoconstrictor responses to vasodilation at most frequencies of stimulation. In the absence of phentolamine pretreatment, even a lower dose of methysergide reversed or caused biphasic responses (attenuated constriction followed by dilatation) during the nerve stimulation at the lower frequencies (0.5-4.0 Hz). This lower dose of methysergide completely abolished vascular effects of exogenous 5-hydroxytryptamine (5-HT) and potentiated those of norepinephrine; hence, the antagonism by methysergide of neurally mediated vasoconstriction is not caused by an action on alpha-adrenergic receptors. Unlike methysergide, selective 5-HT2 antagonists ketanserin and ritanserin have no modifying effect on exogenous 5-HT responses. These studies have provided pharmacological evidence that suggests that 5-HT may be the neurotransmitter mediating neurogenic vasoconstriction in the dog forelimb, and that this effect does not involve activation of 5-HT2 receptors. PMID- 3100344 TI - Applications of hormones in the metabolic regulation of growth and lactation in ruminants. AB - Exogenous natural and synthetic estrogenic and androgenic steroid hormones are used commercially to stimulate metabolic processes associated with increased rate and efficiency of body growth in ruminants. However, mechanisms of action of steroid hormone-induced effects on metabolism are relatively unknown. Application of peptide hormones to muscle growth, fat deposition, and lactation has lagged because of lack of sufficient quantities of the hormones. However, with recombinant DNA technology synthesis of large quantities of peptide hormones is now feasible. Most efforts have focused on growth hormone (GH), growth hormone releasing factor (GRF), and prolactin (PRL) effects on lactation. For example, administration of GH or GRF stimulates yields of milk, milk fat, protein, and lactose as much as 41% in cattle. The mechanism of GH action probably involves somatomedin C acting at extramammary sites and (or) directly at the mammary cell. PRL is lactogenic but has no significant effect on established lactation in cattle. Daily exposure of cattle to 16 h light and 8 h of darkness stimulates milk yield and body growth and reduces fat accretion in the carcass, but the hormonal signals responsible for these photoperiod-induced responses are unknown. Photoperiod manipulations are relatively easy to apply to ruminants, but development of suitable delivery systems for animals will greatly enhance application of peptide hormones to further studies of metabolism as well as commercial livestock production systems. PMID- 3100345 TI - Induction of DNA single-strand breaks and DNA synthesis inhibition in CHO and AWRF cells after exposure to sterigmatocystin and penicillic acid. AB - Sterigmatocystin is 12 times more toxic to transformed rat fibroblasts (AWRF) than to Chinese hamster ovary cells (CHO). In contrast, penicillic acid is twice more toxic to CHO cells than to AWRF cells. The ability of sterigmatocystin and penicillic acid to inhibit DNA synthesis correlated well with the differences in cytotoxicity of these mycotoxins in the cell lines used. Sterigmatocystin at a concentration of 10 micrograms/ml inhibited DNA synthesis in AWRF cells during a 3-h exposure to 60% of that found in controls, but did not inhibit DNA synthesis in CHO cells. Within the same time interval penicillic acid inhibited DNA synthesis in AWRF cells at concentrations higher than 5 micrograms/ml and in CHO cells at concentrations over 0.5 microgram/ml. Induction of DNA single-strand breaks (SSB) during a 3-h exposure to sterigmatocystin and penicillic acid was comparable in both cell types. The results suggest that sterigmatocystin is metabolized to reactive metabolites that are responsible for the toxicity and DNA synthesis inhibition at a more rapid rate in AWRF cells than in CHO cells. The observed ability to induce SSB indicates that penicillic acid is potentially carcinogenic. PMID- 3100346 TI - [Serum free thyroid hormones and response of TSH to TRH in nonthyroidal illnesses]. AB - The change in the levels of free thyroid hormones and the pathophysiology of the hypothalamo-pituitary-thyroid axis of patients with nonthyroidal illness (NTI) have not been clearly elucidated so far. Therefore, it was thought of interest to investigate this problem by determining free thyroid hormones and TSH in serum and the response of TSH to TRH in these patients. The subjects employed in this study were 71 cases with hemodialysis, 40 cases with diabetes mellitus, 24 cases with liver cirrhosis, 12 cases with various cancers, 10 cases with anorexia nervosa and 110 normal subjects as controls. The serum total protein, albumin, free T4, free T3, TSH and other parameters of thyroid function were determined, and the TRH test was performed on about 10 patients of each group. Serum TSH was not only determined by a conventional assay system, but with a highly sensitive method, and the data were compared with one another. It was found that the serum free T3 levels were significantly low in all the groups investigated, but the serum free T4 levels were significantly low only in the groups with hemodialysis, decompensated liver cirrhosis, cancers and anorexia nervosa. No significant lowering of serum free T4 was observed in the patients with diabetes mellitus, acute hepatitis and compensated liver cirrhosis. However, serum TSH levels tended to be higher in all the groups studied, though they were not significant. The response of TSH to TRH was low or delayed in about 20-50% of patients with hemodialysis, diabetes mellitus, liver cirrhosis, cancers and anorexia nervosa. It was observed that the serum rT3 concentration was significantly high in the patients with diabetes mellitus and anorexia nervosa but significantly low in the patients on hemodialysis. In the rest of the groups, there were found many cases who showed high levels of serum rT3 although they were not statistically significant. These results indicate that low concentrations of serum free T3 observed in the majority of the patients with severe NTI were, at least in part, due to the decrease in the peripheral conversion of T4 to T3 and the lowered sensitivity of the anterior pituitary to thyroid hormones and TRH. PMID- 3100347 TI - Theirs is to catch, but not consume. Small scale fishing communities in India. PMID- 3100349 TI - Fish and food aid. PMID- 3100348 TI - The prospects for fish for the malnourished. PMID- 3100350 TI - A nutritional approach to fisheries projects. PMID- 3100351 TI - Research for fisheries and the alleviation of malnutrition. PMID- 3100352 TI - Putting men back in the picture. Sexism in nutrition and extension programmes. PMID- 3100353 TI - Long-term oral acyclovir treatment prevents recurrent genital herpes. AB - Thirty-three patients with frequently recurring genital herpes completed a randomized double-blind, crossover trial with oral acyclovir 200 mg 4 times a day and placebo for periods of 12 weeks. Five patients (15%) had full recurrence during acyclovir treatment and 31 (94%) while receiving placebo. The median time to first recurrence was 20 days for placebo and more than 84 days for acyclovir. It was concluded that acyclovir was well tolerated and an effective treatment to suppress the disease in selected cases of severe and frequently recurring genital herpes. However, the relapses seem to occur with the same rate as before, when the suppressive acyclovir treatment is stopped. PMID- 3100354 TI - Ketoconazole treatment of 13 patients with chronic mucocutaneous candidiasis. A prospective 3-year trial. AB - Long-term results of initial ketoconazole treatment were evaluated in 13 patients with chronic mucocutaneous candidiasis followed up for 3 years. Six of them shared 11 endocrine or autoimmune disorders. All patients responded well to treatment but 1 dropped out owing to anxiety. Clinical and mycological clearing was achieved in 1-2 months for the mouth, 2 months for the skin, 3-4 months for paronychiae and 4-14 months for the nails. Bacterial infections persisted in 2 cases. After withdrawal of ketoconazole, 2 patients have remained in remission. Continuous therapy was required in 2 cases and the others were treated intermittently owing to recurrences of Candida stomatitis. Ketoconazole was well tolerated. An asymptomatic reversible increase of serum hepatic enzymes occurred in 1 case. Oral ketoconazole is the drug of choice for treatment of chronic mucocutaneous candidiasis but long-term observation is required. PMID- 3100355 TI - Evaluation of cefotetan in uncomplicated gonorrhea. AB - Cefotetan is a newly developed cephamycin especially resistant to bacterial beta lactamase. Therefore both its in vitro activity against Neisseria gonorrhoeae and its clinical efficacy in uncomplicated gonorrhea are investigated. The minimal inhibitory concentrations (MIC) lie in the range of 0.016-2 micrograms/ml, 90% of the strains being inhibited by 0.5 microgram/ml. Of 52 finally evaluable patients who were treated by a single intramuscular injection of 1 g, 48 (92.3%) were cured bacteriologically. Thus the present treatment protocol may prove useful in individual cases. It should, however, not be advocated for gonorrhea treatment in general. PMID- 3100356 TI - Neonatal advantage of epidural anesthesia in elective and emergency cesarean sections: a report of 531 cases. AB - In 147 elective and 384 non-elective cesarean sections, the need for neonatal respiratory assistance at birth was significantly greater for babies born under general anesthesia compared to epidural anesthesia, and the differences could not be explained by differences in pre-operative risk factors. For 114 babies on whom blood gas data were gathered prospectively, a greater proportion born under general anesthesia were acidemic and hypercarbic. Our results complement a growing body of retrospective and clinical data suggesting that epidural anesthesia is preferable to general in all but a few cesarean sections. Ideally, this suggestion should be tested in a randomized clinical trial. PMID- 3100357 TI - Treatment with a luteinising hormone-releasing hormone analogue (Buserelin) in danazol-resistant endometriosis patients. AB - Luteinising hormone-releasing hormone agonist (Buserelin) therapy administered for a period of 6 months in 4 patients with longstanding, severe, danazol resistant endometriosis, was found to be effective in reducing all complaints related to endometriosis. From 2 weeks on, nearly half of the E2 determinations were below the sensitivity level of the assay, while the other values were predominantly in the range of the early follicular phase. Side effects associated with the induced hypoestrogenemia were mild and well tolerated. After six months of follow-up without treatment, one patient who desired pregnancy conceived shortly after cessation of therapy and one patient showed lasting amelioration of her complaints. The symptoms relapsed in the other two, possibly due to inadequate dose and/or duration of treatment. PMID- 3100358 TI - Characterization and solubilization of membrane bound diacylglycerol lipases from bovine brain. AB - Bovine brain contains two diacylglycerol lipases. One is localized in purified microsomes and the other is found in the plasma membrane fraction. The microsomal enzyme is markedly stimulated by the non-ionic detergent, Triton X-100, and Ca2+, whereas the plasma membrane diacylglycerol lipase is strongly inhibited by Triton X-100 and Ca2+ has no effect on its enzymic activity. Both enzymes were solubilized using 0.25% Triton X-100. The solubilized enzymes followed Michaelis Menten kinetics. The apparent Km values for microsomal and plasma membrane enzymes are 30.5 and 12.0 microM respectively. Both lipases are strongly inhibited by RHC 80267, with Ki values for microsomal and plasma membrane diacylglycerol lipases of 70 and 43 microM, respectively. The retention of microsomal diacylglycerol lipase on a concanavalin A-Sepharose column and its elution by methyl alpha-D-mannoside indicates the glycoprotein nature of this enzyme. PMID- 3100359 TI - Calcium-, phospholipid-dependent protein kinase activity of cultured rat Sertoli cells and its modifications by vitamin A. AB - The activity of the calcium-, phospholipid-dependent protein kinase (PKc) was partially characterized in Sertoli cell cultures prepared from 20-day-old rats. The calcium dependency, the requirements for phosphatidylserine and diolein, as well as the Km for ATP and for the tumor promoter TPA, were determined in total cell extracts. The specific activity of PKc was almost 3-fold higher in the soluble than in the particulate fraction of Sertoli cells. Treatment of cultured Sertoli cells with retinol inhibited, within 1 h of treatment, both the soluble and the particulate fraction-associated PKc activity, with an IC50 of 0.1 microM. Partial inhibition of PKc activity was obtained treating Sertoli cell cultures with FSH, while testosterone was ineffective. However, both FSH and testosterone potentiated the inhibitory effect of retinol. Less differentiated Sertoli cells, obtained from 8-day-old rats, displayed higher PKc activity and a pattern of subcellular distribution of the enzyme opposite to that of Sertoli cells obtained from 20-day-old rats. These data suggest that the actual PKc activity of rat Sertoli cells be negatively regulated by retinol and, spontaneously, during the progression of Sertoli cell differentiation. PMID- 3100360 TI - Flow cytometry analysis of cells dispersed from the MtTF4 tumor whose growth is inhibited by estradiol treatment. AB - The aim of this work was to determine whether treatments of rats with estradiol (E) in conditions known to decrease the proliferation rate, the mitotic index and the thymidine incorporation into the DNA of the MtTF4 tumor act at a specific point in the cell cycle. Two weeks after grafting a piece of tumor under the kidney capsule, adult male Fischer rats were treated or not treated with E. Tumors were collected between 12 h and 11 days later. Cells were dispersed by collagenase-DNAse treatment and fixed with ethanol. DNA content, cell size, cell granularity and protein content were analyzed, alone or in combination with a flow cytometer. E treatments did not apparently modify the distribution of cells according to their DNA content whereas they did increase dramatically cell size, cell granularity and cell protein content. Simultaneous analysis of DNA content and light scattering or protein content allowed us to demonstrate that there was an increase of a population of large granular and protein-rich cells regardless of the phase of the division cycle considered. These effects are time-dependent, dose-dependent and hormone-specific. This work shows both the interest of flow cytometry to describe the consequences of E treatment at any phase of the cycle of cells dispersed from a solid tumor and the limits of this method in the conditions used to specify the E target points: at the present time, it cannot be decided whether E acts at one or several points of the cell cycle for inhibiting tumor growth. PMID- 3100361 TI - The effect of hypoxanthine on mouse oocyte growth and development in vitro: maintenance of meiotic arrest and gonadotropin-induced oocyte maturation. AB - The concentration of hypoxanthine in mouse follicular fluid has been estimated to be 2-4 mM, and although this concentration maintains meiotic arrest in fully grown mouse oocytes in vitro, oocyte maturation in vivo is not induced by a decrease in the concentration of this purine in follicular fluid (J. J. Eppig, P. F. Ward-Bailey, and D. L. Coleman, Biol. Reprod. 33, 1041-1049, 1985). In the present study, the effect of 2 mM hypoxanthine on oocyte growth and development in vitro was assessed and the ability of gonadotropins to stimulate oocyte maturation in the continued presence of hypoxanthine was determined. Oocyte granulosa cell complexes were isolated from 10- to 11-day-old mice and cultured in the presence or absence of 2 mM hypoxanthine. Oocytes from 10- to 11-day-old mice are in mid-growth phase and, without further development, are incompetent of undergoing meiotic maturation. During a 12-day culture period the granulosa cell enclosed oocytes approximately doubled in size and, regardless of the presence or absence of hypoxanthine, 50-70% developed competence to undergo germinal vesicle breakdown (GVBD). Hypoxanthine promoted the continued association of oocytes with their companion granulosa cells during the 12-day culture period, and therefore had a beneficial effect on oocyte development. Most of the oocytes that acquired GVBD competence in the absence of hypoxanthine underwent spontaneous GVBD. In contrast, 95% of the GVBD-competent oocytes were maintained in meiotic arrest by hypoxanthine. Following withdrawal of the hypoxanthine after the 12-day culture, 75% of the GVBD-competent oocytes underwent GVBD. These results show that hypoxanthine, and/or its metabolites, maintains meiotic arrest in oocytes that grow and acquire GVBD competence in vitro. Follicle-stimulating hormone (FSH), but not luteinizing hormone or human chorionic gonadotropin, induced oocyte GVBD in the continued presence of hypoxanthine. FSH stimulated oocyte maturation at a significantly (P less than 0.01) higher frequency than coculture of the granulosa cell-denuded oocytes with granulosa cells in the continued presence of hypoxanthine. FSH did not induce the maturation of denuded oocytes cocultured with granulosa cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3100362 TI - Formation and maturation of subneural apparatuses at neuromuscular junctions in postnatal rats: a scanning and transmission electron microscopical study. AB - We examined the morphodifferentiation of subneural apparatuses at neuromuscular junctions with scanning and transmission electron microscopy (SEM and TEM) in the sternothyroid muscle of postnatal rats. As evidenced with SEM, primitive synaptic troughs found at birth were smooth cup-like depressions 5-6 micron in diameter. At the 5th postnatal day, low sarcoplasmic ridges appeared in the depression which successively grew and upheaved to remodel the depression into anastomosed gutters during the next 10 days. Subneural apparatuses attained almost the adult form by the 30th day, though synaptic troughs were smaller in size and exhibited a less complex pattern. At birth, the depression contained a few mostly pit-like or elongated oval invaginations:incipient junctional folds. By the 15th day, junctional folds rapidly developed, resulting in about an 18-fold increase in number per endplate with the parallel differentiation of slit-like junctional folds of adult form. At the 30th day, junctional folds were mostly slit-like, though pits still coexisted in a small proportion. As a shape factor, we measured the ratio of the length of the folds to their maximum width (L/W); the folds with L/W less than 2 were defined as pits, those with 2 less than or equal to L/W less than 5 as short slits, and those with L/W greater than or equal to 5 as long slits. At birth, pits occupied about 67% of the total number of the folds per endplate, which decreased to about 14% at the 30th day. Concomitantly, long slits remarkably increased from about 3 to 38%. Short slits increased from about 30 to 50% during the first 10 days but remained almost unchanged thereafter. The maximum L/W ratio was 12 at the 15th day and exceeded 20 after the 30th day. These quantitative data and the finding that pits were often closely associated with each other and also with a slit in a serial fashion indicate that the adjacent pits may fuse to each other and to the preformed slits. With TEM, a few incipient junctional folds were found at the 5th day, which extended into the subneural sarcoplasm with a depth less than 0.4 micron. At the 15th day, junctional folds increased both in number and in the maximum depth of about 0.8 micron. There also occurred a number of basal lamina-containing vacuoles identical in many respects to the transversely sectioned profiles of incipient junctional folds.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3100363 TI - A development genetic analysis of the gene regulator of postbithorax in Drosophila melanogaster. AB - We report the characterization of loss-of-function alleles of the homoeotic mutation Regulator of postbithorax (Rg-pbx) in Drosophila melanogaster. Rg-pbx is a dominant gain-of-function mutation which shows a transformation of posterior haltere to wing in the adult cuticle. This mutant phenotype mimics that of the bithorax complex lesion postbithorax (pbx). Loss-of-function alleles described here are lethal in the embryonic stage and affect the pattern of segmentation of the embryo. Examination of the terminal phenotype of null and hypomorphic alleles of Rg-pbx has shown that inactivation of the Rg-pbx gene leads to loss of the thoracic segments and the adjacent labial segment of the Drosophila embryo. An effect of the mutations is also seen in the seventh and eighth abdominal segments of embryos. The loss-of-function phenotype is similar to that described for the segmentation mutant hunchback (hb). Complementation tests show that Rg-pbx and hb are allelic. Temperature shift experiments using a temperature-sensitive loss-of function allele show that the Rg-pbx gene product is required early in embryogenesis. We further report that the dominant Rg-pbx phenotype is sensitive to the gene dosage of another segmentation-controlling gene, fushi tarazu (ftz). Flies carrying a mutant copy of the ftz gene in trans to Rg-pbx show a dramatic enhancement of the penetrance of the homoeotic mutant phenotype. We were also able to demonstrate a suppression of the Rg-pbx phenotype by the addition of a duplication for the ftz+ gene to an Rg-pbx stock. Examination of the phenotype of ftz Rg-pbx- double-mutant embryos did not reveal a clear pattern of epistasis between the genes nor was absolute additivity of phenotype seen. A possible formal relationship between Rg-pbx, ftz, and the postbithorax (pbx) locus is proposed. PMID- 3100364 TI - Localization of zona pellucida binding sites on rabbit spermatozoa and induction of the acrosome reaction by solubilized zonae. AB - The binding of mammalian spermatozoa to the egg's extracellular coat, the zona pellucida, is a complex process which culminates in species-specific penetration of the sperm to the egg plasma membrane. To investigate where on the spermatozoon's surface the zona binding sites are located, whole rabbit zonae were labeled with FITC, heat solubilized and used to observe the surface binding patterns on live spermatozoa. Before the acrosome reaction the zona binding sites are located either over the entire head as well as the middle piece or alternatively in patches along the apical ridge of the head. After the acrosome reaction there is a 29% loss of fluorescence and the zona binding sites are present in the posterior aspect of the acrosomal region, the anterior postacrosomal region and the middle piece. These results demonstrate the presence of zona binding sites after the acrosome reaction which would account for the sperm's ability to remain bound to the zona after the acrosome reaction. Further, we report for the first time that solubilized rabbit zonae pellucidae will induce the acrosome reaction in in vitro capacitated rabbit sperm whereas solubilized pig zonae pellucidae will not. Since rabbit sperm bind pig zonae, the induction and specificity of the physiological acrosome reaction must reside in the affinity of the binding rather than the binding itself. PMID- 3100365 TI - Effect of glyburide on glycemic control, insulin requirement, and glucose metabolism in insulin-treated diabetic patients. AB - Glycemic control and glucose metabolism were examined in 5 patients with insulin dependent diabetes mellitus (IDDM) and 8 insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) patients before and after 2 mo of therapy with glyburide (20 mg/day). Glycemic control was assessed by daily insulin requirement, 24-h plasma glucose profile, glucosuria, and glycosylated hemoglobin. Insulin secretion was evaluated by glucagon stimulation of C-peptide secretion, and insulin sensitivity was determined by a two-step euglycemic insulin clamp (1 and 10 mU X kg-1. X min-1) performed with indirect calorimetry and [3-3H]glucose. In the IDDM patients, the addition of glyburide produced no change in daily insulin dose (54 +/- 8 vs. 53 +/- 7 U/day), mean 24-h glucose level (177 +/- 20 vs. 174 +/- 29 mg/dl), glucosuria (20 +/- 6 vs. 35 +/- 12 g/day) or glycosylated hemoglobin (10.1 +/- 1.0 vs. 9.5 +/- 0.7%). Furthermore, there was no improvement in basal hepatic glucose production (2.1 +/- 0.2 vs. 2.4 +/- 0.1 mg X kg-1 X min-1), suppression of hepatic glucose production by low- and high-dose insulin infusion, or in any measure of total, oxidative, or nonoxidative glucose metabolism in the basal state or during insulin infusion. C peptide levels were undetectable (less than 0.01 pmol/ml) in the basal state and after glucagon infusion and remained undetectable after glyburide therapy. In contrast to the IDDM patients, the insulin-treated NIDDM subjects exhibited significant reductions in daily insulin requirement (72 +/- 6 vs. 58 +/- 9 U/day), mean 24-h plasma glucose concentration (153 +/- 10 vs. 131 +/- 5 mg/dl), glucosuria (14 +/- 5 vs. 4 +/- 1 g/day), and glycosylated hemoglobin (10.3 +/- 0.7 vs. 8.0 +/- 0.4%) after glyburide treatment (all P less than or equal to .05). However, there was no change in basal hepatic glucose production (1.7 +/- 0.1 vs. 1.7 +/- 0.1 mg X kg-1 X min-1), suppression of hepatic glucose production by insulin, or insulin sensitivity during the two-step insulin-clamp study. Both basal (0.14 +/- 0.05 vs. 0.32 +/- 0.05 pmol/ml, P less than .05) and glucagon stimulated (0.24 +/- 0.07 vs. 0.44 +/- 0.09 pmol/ml) C-peptide levels rose after 2 mo of glyburide therapy and both were correlated with the decrease in insulin requirement (basal: r = .65, P = .08; glucagon stimulated: r = .93, P less than .001).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3100366 TI - Insulin response in individual tissues of control and gold thioglucose-obese mice in vivo with [1-14C]2-deoxyglucose. AB - The dose-response characteristics of several glucose-utilizing tissues (brain, heart, white adipose tissue, brown adipose tissue, and quadriceps muscle) to a single injection of insulin have been compared in control mice and mice made obese with a single injection of gold thioglucose (GTG). Tissue content of [1 14C]2-deoxyglucose 6-phosphate and blood disappearance rate of [1-14C]2 deoxyglucose (2-DG) were measured at nine different insulin doses and used to calculate rates of 2-DG uptake and phosphorylation in tissues from control and obese mice. The insulin sensitivity of tissues reflected in the ED50 of insulin response varied widely, and brown adipose tissue was the most insulin-sensitive tissue studied. In GTG-obese mice, heart, quadriceps, and brown adipose tissue were insulin resistant (demonstrated by increased ED50), whereas in white adipose tissue, 2-DG phosphorylation was more sensitive to insulin. Brain 2-DG phosphorylation was insulin independent in control and obese animals. The largest decrease in insulin sensitivity in GTG-obese mice was observed in brown adipose tissue. The loss of diet-induced thermogenesis in brown adipose tissue as a result of the hypothalamic lesion in GTG-obese mice could be a major cause of insulin resistance in brown adipose tissue. Because brown adipose tissue can make a major contribution to whole-body glucose utilization, insulin resistance in this tissue may have a significant effect on whole-animal glucose homeostasis in GTG-obese mice. PMID- 3100367 TI - No evidence for increased growth hormone responses to growth hormone-releasing hormone in patients with diabetic retinopathy. AB - Several studies report increased growth hormone (GH) responses to provocative stimuli in patients with diabetic retinopathy. We studied GH responses to 1 microgram/kg body wt human pancreatic GH-releasing hormone 1-44 (hpGHRH 1-44) in 33 patients with type I diabetes mellitus, 31 patients with type II diabetes mellitus, and 2 control groups (N = 11 and 8). Based on the results of fundoscopy and fluorescein angiography, the diabetic patients were subdivided into patients without diabetic retinopathy, patients with nonproliferative diabetic retinopathy, and patients with proliferative diabetic retinopathy. Growth hormone responses to hpGHRH 1-44 in diabetic patients with proliferative or nonproliferative retinopathy or without retinopathy were not significantly different regardless of the type of diabetes. Remarkably, GH responses to hpGHRH 1-44 in type I diabetic patients without retinopathy were significantly higher than the matched controls. Our data suggest that diabetic retinopathy in type I and in type II diabetes is not associated with increased GH responsiveness to hpGHRH 1-44, whereas in type I diabetes mellitus without diabetic retinopathy, a GH hyperresponsiveness to hpGHRH seems to occur. PMID- 3100369 TI - Evidence for existence of polyol pathway in cultured rat mesangial cells. AB - The accumulation of polyols has been previously found in renal glomeruli isolated from streptozocin-induced diabetic (STZ-D) rats, although the intraglomerular polyol pathway has not been exactly localized. Because we have previously observed mesangial cell dysfunction in STZ-D rats, we examined whether the polyol pathway exists in mesangial cells as a possible candidate of the cause of cellular dysfunction. The activities of two polyol pathway enzymes, aldose reductase and sorbitol dehydrogenase, were clearly detected in the crude homogenate of cultured mesangial cells at higher levels than those of whole glomeruli when DL-glyceraldehyde or D-fructose was used as substrate. When cells were incubated in medium containing 55 mM glucose or galactose, a large amount of sorbitol or galactitol was accumulated intracellularly. The accumulation of polyols was effectively blocked by an aldose reductase inhibitor, ICI 128436. These results suggest that the polyol pathway exists in mesangial cells of rat glomeruli and may play a role in the development of mesangial cell dysfunction found in STZ-D rats. PMID- 3100368 TI - Decreased uptake of glucose by human forearm during infusion of leucine, isoleucine, or threonine. AB - Competition between glucose and free fatty acids as metabolic fuels is supported by both in vitro and in vivo data, but whether amino acids can also compete with glucose as a source of energy in vivo remains to be established. To determine the effect of increased availability of an amino acid on whole-body glucose flux and glucose carbon uptake by the human forearm, five groups of overnight-fasted normal subjects were infused with either saline, leucine (at 0.5 or 1.0 mumol X kg-1 X min-1), isoleucine (0.5 mumol X kg-1 X min-1), or threonine (0.5 mumol X kg-1 X min-1). Plasma glucose concentrations and glucose flux decreased similarly in all groups. No significant changes in forearm output of leucine carbon, isoleucine carbon, or threonine were seen during saline infusion. In contrast, during leucine infusion there was a dose-dependent increase (r = .86, P less than .001) in leucine carbon uptake with increased arterial leucine and alpha ketoisocaproate concentrations. During infusions of isoleucine and threonine, increases (P less than .05) in isoleucine carbon uptake and threonine uptake, respectively, were observed. Glucose uptake by forearm tissues did not change during the saline infusion, but it decreased (P less than .05) in all four groups receiving an amino acid infusion. Changes in leucine carbon uptake were strongly correlated (r = -.76, P less than .001) with changes in glucose uptake. Therefore, amino acids affect glucose uptake in human forearm tissue and presumably compete as oxidative fuels. PMID- 3100370 TI - Effect of anti-Ia antibodies, culture, and cyclosporin on prolongation of canine islet allograft survival. AB - Evidence in rodents suggests that islet pretreatment to reduce islet immunogenicity will also require some form of immunosuppression of the recipient for islet allograft acceptance in highly reactive donor-recipient pairs. We attempted to ascertain whether outbred dogs would also require treatment of both donor islets and the recipient to prolong islet allograft survival. Untreated canine islets are uniformly rejected in 6-10 days in beagles. Tissue culture alone, at 37 degrees C for 7 days, or treatment of freshly prepared islets with anti-Ia monoclonal antibodies (MoAbs) (B1F6 + 7.2) did not prolong canine islet allograft survival. Treatment of culture-maintained canine islets with anti-Ia MoAbs plus complement resulted in prolongation of islet allograft survival for 188 and 368 days in two of seven pancreatectomized nonimmunosuppressed beagles. The administration of low doses of cyclosporin A (CsA) intramuscularly, to recipients of untreated canine islet allografts had no effect on graft survival. By contrast, six of nine CsA-treated recipients of islets that were also treated with anti-Ia MoAbs (B1F6 + 7.2) plus complement showed prolongation of graft survival. Euglycemia was sustained for 19, 34, 89, and 300 days after the CsA was discontinued (day 30) in four of these animals. Two animals had unstable grafts from the beginning that failed 23 and 29 days after transplantation. Our results indicate that simple maneuvers like short-term tissue culture at 37 degrees C and treatment of freshly isolated islets with anti-Ia MoAbs and complement are inadequate to prevent rejection in outbred pancreatectomized beagles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100371 TI - Allotransplantation of islet endocrine aggregates. AB - Dissociated pancreatic islets form endocrine aggregates from single-cell suspension by rotation culture. Islet cell aggregates, or neoislets, can provide endocrine reconstitution for diabetic rats and enjoy prolonged graft survival when neoislets are transplanted across a major histocompatibility barrier (Lewis to ACI). Long-term survival of grafted neoislets was obtained in 71% of recipients without any immunosuppression and in 100% of recipients with minimal immunosuppression. As predicted by cell-cell recognition in rotation-mediated aggregation, neoislets apparently exclude mesenchymal cells that bear la antigens. Therefore, reduced immunogenicity is accomplished. PMID- 3100373 TI - Personal and continuing medical care. PMID- 3100372 TI - Muscle enzyme activity and insulin sensitivity in type 1 (insulin-dependent) diabetes mellitus. AB - The mechanisms of insulin insensitivity in diabetes are poorly understood. We have therefore assessed the relationship between glucose disposal during a euglycaemic clamp, muscle glycogen formation, and the activities of insulin regulated enzymes within skeletal muscle in five Type 1 (insulin-dependent) diabetic patients, both on conventional injection therapy (HbA1 11.0 +/- 1.0 (SD) %) and after 6 weeks continuous subcutaneous insulin infusion (HbA1 7.6 +/- 1.4%, p less than 0.01). On both regimens, overnight euglycaemia before the clamp was maintained with an intravenous insulin infusion. The increase in clamp glucose requirements (insulin 0.1 U X kg-1 X h-1) between injection therapy and continuous subcutaneous insulin infusion was significant (6.2 +/- 0.9 (SE) to 7.0 +/- 0.9 mg X kg-1 X min-1, p less than 0.05), but small compared to differences between subjects. Glucose requirement remained lower than in control subjects (10.4 +/- 0.7 mg X kg-1 X min-1, p less than 0.05). The increase in muscle glycogen with the clamp was slightly higher on continuous subcutaneous insulin infusion (9.5 +/- 2.5 mg/g protein) than on injection therapy (8.5 +/- 2.4 mg/g, p less than 0.05), but less than in control subjects (17.9 +/- 2.1 mg/g, p less than 0.05). The expressed activity of glycogen synthase and pyruvate dehydrogenase increased significantly between fasting and the end of the clamps in the patients (p less than 0.001 and less than 0.005), but was not significantly different between the two treatment regimens. Expressed glycogen synthase activity at the end of the clamp was lower on both treatments than in control subjects (p less than 0.05). Both enzyme activities were, however, highly correlated with glucose requirement between patients, (r = 0.89-0.94, p less than 0.05-0.02), and glycogen synthase was similarly correlated in the control subjects (r = 0.84, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100374 TI - [Malignant ventricular tachyarrhythmias: guided therapy by serial electropharmacologic study]. PMID- 3100375 TI - [Association of autoimmune chronic active hepatitis and acquired erythroblastopenia cured by cyclophosphamide]. AB - To the best of our knowledge this is the reported first case of the successive occurrence in the same patient of chronic active hepatitis and acquired pure red cell aplasia, both probably of autoimmune origin. The diagnosis of autoimmune hepatitis was based on the presence of characteristic lesions at the examination of the liver biopsy specimen, high titer of anti-smooth muscle antibodies in the serum, and remission obtained by steroid therapy. Erythroid aplasia, which appeared during the course of this treatment, was revealed by a regenerative anemia (4.4 g Hb/100 ml) and proved by bone marrow aspiration and biopsy. In vitro bone marrow culture was normal, suggesting the in vivo presence of an inhibitor of erythroblastic differentiation. Red cell aplasia was cured by cyclophosphamide (100 mg/day during 56 days). No recurrence was noted until the death of the patient, which occurred one year later, due to hepatic cholangiocarcinoma. Action of cyclophosphamide on the pure red cell aplasia suggested the immune origin of this disease. The liver and the bone marrow erythroid lineage have probably been the successive targets of immunologic dyscrasia. PMID- 3100376 TI - Endoscopic removal of entrapped coins from an intraluminal duodenal diverticulum 20 years after ingestion. PMID- 3100377 TI - [Premature menopause]. AB - In 46 patients with the diagnosis of "premature menopause" menstrual history, clinical findings and hormonal quantitations were analysed. This clinical entity was evaluated with regard to a rapid verification of the diagnosis. The age of the investigated women with secondary failure to menstruate varied between 13 to 39 years (mean value 29 years). Menstrual history varied considerably. 20 women complained about menopausal symptoms. 5 women had adnexal operations before. Vaginal hormonal cytology, gestagen test and quantitation of the circulating oestradiol concentrations were of little value for establishing the diagnosis, since many of these women revealed premenopausal oestradiol levels. Quantitation of FSH is decisive for establishing the diagnosis. In women under the age of 40 with FSH values above 1000 ng LER 907/ml or above 40 mIU/ml premature ovarian failure can be assumed; however, in individual cases the "gonadotropin resistant ovary syndrome" must be differentiated. PMID- 3100378 TI - [Vulvar cancer in a 13-year-old girl]. AB - A case of squamous cell carcinoma of the vulva in a 13-year old girl is reported. The disease progressed inspite of radiotherapy and the patient died five months later. In the past 115 years only 35 malignomas of the vulva in children and adolescents have been reported, including our case. Most tumours were either of embryonic origin or sarcomas. PMID- 3100379 TI - [Prognosis of primary radiotherapy of cervix cancer in younger females]. AB - Between 1970 and 1979 202 women of 40 years of age or younger were treated for invasive cervical cancer at the 1st Department of Obstetrics and Gynaecology of the University of Vienna. 77 patients received primary irradiation therapy (radium and cobalt-60), 125 underwent surgery. These cases were compared with 1586 patients of all ages who received primary radiation therapy. Of the women under 40 receiving only radiation therapy, the survivors were divided into the following categories: stage I:84.6% of 13 cases stage II:69.2% of 13 cases stage III:35.1% of 37 cases stage IV: 0% of 14 cases. The survival rate for all age groups receiving primary radiation therapy was: stage I:76.0% of 225 cases stage II:52.9% of 429 cases stage III:42.9% of 801 cases stage IV:11.4% of 131 cases. There was no significant difference in the 5-year survival rate between the older and younger women. However, a more promising trend for the younger women receiving primary radiation therapy may be expected. The younger women were observed to have irreversible complications (fistulas) at a rate of 7.7%, whereas the rate of comparable patients receiving radiation therapy was 0.6%. The younger women having stage III and IV cancer were found to develop fistulas at a rate of 17.6%, while both groups together had a rate of only 3.2%. Hence, primary radiation therapy for younger women must be considered as involving a relatively high rate of complications. For younger women with stage I cancer the survival rate after radical surgery was 88.8% (98 cases), after radiation therapy 84.6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100380 TI - [Improved implantation rate following embryo transfer in an in vitro fertilization program]. AB - In spite of the efforts made in in-vitro fertilization and embryo transfer in recent years, little progress has so far been made with regard to the pregnancy rate. While embryo transfer rates of over 80% are now being attained, the pregnancy rate achieved with extracorporal fertilization in the majority of study groups is well under 20%. Between 1981 and May 1986, 1088 laparoscopies were performed in our study group with the aim of follicle puncture and subsequent in vitro fertilization and embryo transfer. A total of 171 pregnancies resulted from 832 embryo transfers. The pregnancy rate has been increased since 1981 to 21.2% at present (1986). Since April 1986 we have been using a modified embryo transfer procedure: in 25 patients embryo transfer has been accomplished under barbiturate anesthesia. Twelve of these patients have become pregnant, i.e., 48% of the embryo transfers. There are signs that this embryo transfer method will lead to a distinct improvement in the pregnancy rate. An attempt should be made to confirm these provisional results in a larger collective. PMID- 3100381 TI - [Principles of medical genetic consultation in hemophilia A]. PMID- 3100382 TI - [Discriminant analysis of the heterozygote carrier state for hemophilia A]. PMID- 3100383 TI - [Humoral immunity factors of donors immunized with rhesus system antigens and staphylococcal anatoxin]. PMID- 3100384 TI - Effects of mammalian gonadotropins (oFSH and oLH) on testicular development in the immature water snake, Nerodia sipedon. AB - Ovine FSH (oFSH) or ovine LH (oLH) was injected into immature male Nerodia sipedon and was assessed as to its effects on testicular development and steroid synthesis as indicated by the subsequent development of the renal sexual segment, a known secondary sexual character. FSH-injected animals had significantly larger testis mass, seminiferous tubule diameter, and epithelial height when compared to LH-injected and control groups. While FSH induced testicular development, LH induced lipid accumulation and hypertrophy of the mitochondria in the Leydig cell, indicative of androgen production. While both FSH and LH induced development of the renal sexual segment, LH stimulated the production of sexual granules prior to FSH, implying that androgens enter the circulation faster under LH treatment. PMID- 3100385 TI - In vitro study of frog (Rana ridibunda Pallas) neurointermediate lobe secretion by use of a simplified perifusion system. IV. Interaction between dopamine and thyrotropin-releasing hormone on alpha-melanocyte-stimulating hormone secretion. AB - The interaction between dopamine and TRH on alpha-melanocyte-stimulating hormone (MSH) release from the intermediate lobe of amphibian pituitary has been studied in vitro using the perifusion model. Dopamine (10(-10) to 10(-6) M) was responsible for a dose-related inhibition of alpha-MSH secretion. The inhibitory effect of dopamine (10(-8) and 3.16 X 10(-8) M) was completely abolished in the presence of haloperidol (10(-5) and 10(-6) M, respectively). It has been previously established that, in amphibians, TRH stimulated alpha-MSH release in vitro and that the action of TRH was not mediated via an inhibition of the release of endogenous dopamine (M. C. Tonon, P. Leroux, M. E. Stoeckel, S. Jegou, G. Pelletier, and H. Vaudry, 1986, Endocrinology 112, 133-141). In the present study we demonstrate that TRH (10(-7) M) reverses the inhibitory effect of dopamine (for concentrations ranging from 3.16 X 10(-8) to 10(-6) M) on alpha-MSH secretion and that the effects of TRH and dopamine are additive. Thus, these results indicate that the intracellular events associated with TRH-induced stimulation and dopamine-induced inhibition of alpha-MSH release are not linked together. PMID- 3100386 TI - Effects of two kinds of chicken luteinizing hormone-releasing hormone (LH-RH), mammalian LH-RH and its analogs on the release of LH and FSH in Japanese quail and chicken. AB - A newly isolated and characterized chicken luteinizing hormone-releasing hormone II (chicken LH-RH-II, Miyamoto et al., 1984) had luteinizing hormone (LH) and follicle-stimulating hormone (FSH) releasing activity in vitro and in vivo in Japanese quail: the activity was almost equal to chicken LH-RH-I and mammalian LH RH. These three LH-RHs induced the release of LH several times higher than that of FSH in vitro and also in vivo. No significant difference between chicken LH-RH I and LH-RH-II was observed in LH releasing activity in vitro using chicken pituitary gland in the same incubating condition as in quail. Another experiment indicated that no synergism existed between chicken LH-RH-I and -II and that there was neither LH nor FSH releasing activity in [D-Phe2, Pro3, D-Phe6]-LH-RH or in mesotocin. However, the same potency as in the chicken LH-RH-II was observed in [D-Ala6, des-Gly10]-LH-RH ethylamide, a superactive analog in mammals. The results indicate that an avian adenohypophysis differs from a mammalian adenohypophysis in its responsiveness to LH-RH suggesting that an avian LH-RH receptor may have a lower specificity in "recognition" of LH-RH molecules than a mammalian LH-RH receptor has. PMID- 3100387 TI - Plasma sex-steroid binding protein in a seasonally breeding reptile, Alligator mississippiensis. AB - The properties of a sex-steroid binding protein (SSBP) in the plasma of the American alligator, Alligator mississippiensis, were partially characterized. Alligator SSBP has a sedimentation coefficient of 4S in a 5-20% sucrose gradient. It binds to estradiol-17 beta (E2) and testosterone (T) with limited capacities and moderate affinities (association constant for [3H]E2 is 4.70 +/- 0.09 X 10(8) M-1 and for [3H]T is 1.05 +/- 0.07 X 10(8) M-1, mean +/- SEM of six determinations). Plasma SSBP level, as measured by plasma [3H]E2 binding capacity, varies from 30 to 140 nmol per liter plasma (nM) and was found to be dependent on the gender, sexual maturity, and reproductive state of the animal. Distinct annual fluctuations in plasma SSBP level were observed in female alligators. In adult females, plasma SSBP levels were high (122 +/- 6 nM) in the fall during the nonbreeding season and low (30-60 nM) in spring and early summer during the breeding season. A minimum (33 +/- 6 nM) was reached in mid-June coinciding with the time of oviposition and rapid decline in circulating estrogen levels. This decline in adult female plasma SSBP levels during the breeding season was not observed in immature females. On the contrary, plasma SSBP levels in immature females increased from 81 +/- 14 nM in April to 134 +/- 9 nM in June. Plasma SSBP levels in male alligators showed little changes throughout the entire breeding season; they remained within the range of 80-100 nM from March to June. We believe that seasonal fluctuations in plasma SSBP levels constitute part of the mechanism involved in the regulation of free steroid delivered to target organs in female alligators and that such a mechanism does not exist in male animals. PMID- 3100388 TI - Calcium participation in thyroid function in fowl (Gallus domesticus). AB - The effects of the calcium antagonists ethyleneglycol-bis-(beta-aminoethylether) N,N,N',N'-tetraace tic acid (EGTA), cobalt chloride (CoCl2), and magnesium chloride (MgCl2) on the concentrations of plasma thyroxine (T4) and triiodothyronine (T3) and on the basal and stimulated release of T4 from incubated thyroid glands have been determined in the domestic fowl. Plasma T4 levels were consistently reduced 2 hr after the administration of each calcium antagonist, although only EGTA and CoCl2 lowered the concentration of plasma total calcium. Concentrations of plasma T3 were increased following MgCl2 treatment but reduced after CoCl2 administration. The basal release of T4 by incubated thyroid glands was reduced following in vivo EGTA and CoCl2 treatment, but increased after MgCl2 injection. The addition of bovine thyroid stimulating hormone (TSH, 200 mU) to the incubation consistently stimulated in vitro T4 release, although the magnitude of the stimulation was increased following in vivo EGTA or CoCl2 treatment and reduced after MgCl2 administration. These results demonstrate the involvement of calcium dependent mechanisms in the control of T4 release in fowl. PMID- 3100389 TI - Sterility and hypermutability in the P-M system of hybrid dysgenesis in Drosophila melanogaster. AB - Inbred wild strains of Drosophila melanogaster derived from the central and eastern United States were used to make dysgenic hybrids in the P-M system. These strains possessed P elements and the P cytotype, the condition that represses P element transposition. Their hybrids were studied for the mutability of the P element insertion mutation, snw, and for the incidence of gonadal dysgenesis (GD) sterility. All the strains tested were able to induce hybrid dysgenesis by one or both of these assays; however, high levels of dysgenesis were rare. Sets of X chromosomes and autosomes from the inbred wild strains were more effective at inducing GD sterility than were sets of Y chromosomes and autosomes. In two separate analyses, GD sterility was positively correlated with snw mutability, suggesting a linear relationship. However, one strain appeared to induce too much GD sterility for its level of snw destabilization, indicating an uncoupling of these two manifestations of hybrid dysgenesis. PMID- 3100391 TI - [Inversion of the metE-oriC-rpsE chromosome segment in Escherichia coli K12]. AB - We have described recently a large inversion of the Escherichia coli chromosome (designated udpPf1), including region of the chromosomal replication region (oriC). The udpPf1 inversion was induced by Tn10 transposon (metE::Tn10). It results in increased expression of the uridine phosphorylase gene (udp) which is closely linked to the metE gene. The data of conjugational and transductional experiments presented in this report demonstrate that the udpPf1 inversion covers a chromosomal segment extending over 12 min of the E. coli genetic map and including the rpsE, crp and metE::Tn5 markers. The results are presented indicating that the increased uridine phosphorylase activity is due to fusion of the udp gene to a more strong promoter located, probably, in the operon for ribosomal proteins cluster, near 73 min on the E. coli chromosome. PMID- 3100390 TI - Rearrangement of genes located on homologous chromosomal segments in mouse and man: the location of genes for alpha- and beta-interferon, alpha-1 acid glycoprotein-1 and -2, and aminolevulinate dehydratase on mouse chromosome 4. AB - Gene mapping studies to determine the order of alpha- and beta-interferon (Ifa, Ifb), aminolevulinate dehydratase (Lv), and alpha-1 acid glycoprotein-1 and -2 (Orm-1, Orm-2) relative to each other and to the reference genes brown (b), B cell maturation factor responsiveness (Bmfr-1), and major urinary protein-1 (Mup 1) are reported. The most likely order was Mup-1--Lv--b--Orm-1, Orm-2--Ifa, Ifb- Bmfr-1. This order suggested that two chromosomal segments located on chromosome 4 in the mouse and chromosome 9 in man have been conserved since divergence of lineages leading to man and mouse; these segments are marked by soluble aconitase 1 (Aco-1) and galactose-1 phosphate uridyl transferase (Galt) and by Lv and Orm 1. This order also demonstrated that, although genes located on opposite arms of chromosome 9 in man remain syntenic in the mouse, gene order has not been conserved; Ifa and Ifb are not located in their expected locations near Aco-1 and Galt. The position of Ifa and Ifb between Orm-1 and Bmfr-1 could not be determined with certainty because of apparent heterogeneity in recombination frequencies between crosses involving conventional laboratory strains of mice and crosses involving interspecific matings between laboratory mice and Mus spretus. This result suggests that caution must be exercised when using M. spretus in linkage crosses. PMID- 3100392 TI - [Transfer of chromosomal genes and formation of R'-derivatives using PR4::D312cts15 plasmids in Pseudomonas aeruginosa cells]. AB - Several hybrid RP4 plasmids containing the genome of heat-inducible D3112cts15 phage integrated into 2 different sites of RP4 were selected. It was shown that the plasmids RP4::D3112cts15 mobilized the chromosome of Pseudomonas aeruginosa from many sites located in different chromosome regions. Chromosomal recombinants are, formed at frequencies of about 10(-4) per recipient cell. Analysis of coinheritance of unselected markers showed that the majority of recombinants inherited short donor chromosome fragments (about 5 min). R' plasmids can be easily selected by mating with a rec- recipient. For instance, the frequency of selection of R' plasmids containing argH+ locus was about 10(-5) per donor cell. Conjugative transfer of RP4::D3112cts15 into nonlysogenic strains PAO P. aeruginosa results in partial or complete loss of prophage from a hybrid plasmid. The RP4::D3112cts15 plasmids appear to have retained the broad host range of the original RP4 (they are maintained in P. putida and Escherichia coli). PMID- 3100393 TI - Nucleotide sequence of the sucrase gene of Bacillus subtilis. AB - The sucrase gene (sacA) and part of the sacP locus, which corresponds to a membrane component of the phosphotransferase system (PTS) of sucrose transport of Bacillus subtilis, were previously cloned on a 2.1-kb EcoRI DNA fragment. Genes sacA and sacP were localized on this DNA fragment and the nucleotide sequence of the 2.1-kb DNA fragment was determined. A 1440-bp open reading frame (480 codons) was identified coding for a deduced polypeptide of Mr54827, which corresponds to that of purified sucrase. The amino acid sequence shares homology with that of yeast invertase (SUC2 gene product). The sacA gene and the preceding sacP gene seem to belong to the same operon. PMID- 3100394 TI - A Bacillus subtilis dnaG mutant harbours a mutation in a gene homologous to the dnaN gene of Escherichia coli. AB - A dnaG mutation of Bacillus subtilis, dnaG5, was found to be linked closely to recF. We have reported previously that two putative dna genes, 'dnaA' and 'dnaN', highly homologous to Escherichia coli's dnaA and dnaN, respectively, were located adjacent to recF [Ogasawara et al., EMBO J., 4 (1985) 3345-3350]. Transformation by various fragments cloned from the 'dnaA'-recF region of the wild-type cell revealed that a 532-bp AluI fragment containing 5'-portion of the 'dnaN' gene could transform the dnaG5 mutation. The nucleotide (nt) sequence of the same fragment cloned from the mutant cell shows a single nt change in the ORF of 'dnaN' which in turn causes a single amino acid alteration from Gly to Arg. The 'dnaN' gene is now proven to be a dna gene, mutations in which result in instant arrest of chromosomal replication. PMID- 3100395 TI - A linear shuttle vector for yeast and the hypotrichous ciliate Stylonychia. AB - A linear plasmid was constructed in vitro using the telomeres of the rDNA of Tetrahymena pyriformis. These telomeres were added to a yeast circular vector containing an ARS sequence from Dictyostelium, the LEU2 gene of yeast and the neo gene from Escherichia coli Tn5 fused with a eukaryotic promoter. The resulting plasmid was used to transform yeast. During the replication of the linear plasmid in yeast it was spontaneously modified at the extremity by the addition of 300 bp of yeast telomeric sequence for each end. Total DNA prepared from yeast transformants was used to transform the hypotrichous ciliate Stylonychia lemnae. The same plasmid isolated from Stylonychia can again be replicated in yeast. PMID- 3100397 TI - Compassionate withholding of feeding: are physicians protected? PMID- 3100396 TI - Hyperproduction of an intracellular heterologous protein in a sacUh mutant of Bacillus subtilis. AB - The sacR regulatory region which controls inducible expression of sacB, the gene for extracellular levansucrase, was isolated on a 500-bp fragment of Bacillus subtilis chromosomal DNA. The region was separated into two components: a 325-bp fragment which carries a constitutive promoter and a 175-bp fragment which carries a stem-loop structure presumably involved in the induction process. The constitutive sacR promoter was used to drive expression of the plasmid-borne xylE gene, coding for intracellular catechol 2,3-dioxygenase (C23O), with its Pseudomonas ribosome-binding site, in otherwise isogenic sacU-, sacU+ and sacUh mutant strains of B. subtilis. Mutations at the sacU locus have been previously shown to affect multiple cell functions, particularly production of extracellular enzymes. The presence of the sacUh mutation allowed for hyperproduction of C23O to levels exceeding 25% of total cellular protein. This represents a 50- to 100 fold enhancement over levels observed in sacU- and sacU+ host cells. A 5- to 10 fold improvement of C23O production in sacUh cells was observed when the subtilisin (aprA) promoter was used in place of sacR. In contrast, a bacteriophage T5 synthetic promoter was found to be independent of host strain for high-level synthesis of C23O. Hyperproduction of an intracellular protein in sacUh cells suggests that enhancement of exoenzyme production, previously observed in these mutants, occurs prior to the secretion event. Therefore, hyperproduction is most likely due to elevated transcription or translation of specific nucleotide sequences. PMID- 3100398 TI - [Effect of therapeutic plasmapheresis on the blood coagulation process in pregnant women with serologic Rh incompatibility]. PMID- 3100400 TI - Speaking out on nasogastric feeding. PMID- 3100399 TI - Immunopathology of guinea pig autoimmune enterocolitis induced by alloimmunisation with an intestinal protein. AB - An enterocolitis has been induced in guinea pigs by alloimmunisation with a mucosal protein. A single dose of immunogen fails to provoke a synthesis of precipitant antibodies, but a high percentage of animals, injected with two or more doses, develop these antibodies. A specific cell mediated immune response was already detectable 30 days after a single dose of immunogen. At later periods and after multiple doses of immunogen positive results were still found, although in a lesser percentage of the animals. The pathology was characterised by the appearance of multiple mucosal ulcerations, congestion, oedema and localised haemorrhage. The target organs were mainly ileum and descending colon. At later periods a combination of mononuclear cell infiltration, fibrocytic proliferation and granuloma formation appeared together with the other lesions. When an intraluminal challenge was made 48 hours before death, a heavy mononuclear cell infiltration was present in the contact area. The lesions appeared to extend to areas which usually remained unaffected. The characteristic immunopathology of this autoimmune enterocolitis in guinea pigs possesses some of the features of human inflammatory bowel diseases and makes it a useful model for further studies. PMID- 3100401 TI - Courtship and copulation in Tarsius bancanus. AB - The reproductive behavior of 6 paired, captive Bornean tarsiers was studied over an 8-month period. Seven copulations were observed. Females signalled males by visual displays and olfactory cues from vulval rubbing. Males signalled females with courtship calls heard before matings. After a courtship lasting from 1 to 2 h, copulation occurred with the male thrusting 61-190 times for 60-90 s, ending in ejaculation. The female regulated timing of mating by rejection or avoidance of the male. Multiple matings were not observed, and mating occurred once or twice a night during each night of estrus. This copulatory pattern of infrequent matings of short duration and active female solicitation and regulation of copulating timing suggests a harem or monogamous system. PMID- 3100402 TI - No evidence of carcinogenicity of D-mannitol and propyl gallate in F344 rats or B6C3F1 mice. AB - Chronic toxicity and carcinogenicity studies were conducted on D-mannitol and propyl gallate in F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were maintained on diets containing either 0, 2.5 or 5.0% D-mannitol or 0, 0.6 or 1.2% propyl gallate for 103 wk. D-Mannitol had no effect on survival or mean body weight of rats and mice, and feed consumption was approximately the same in control and treated groups in each species. Gastric fundal gland dilation occurred at a higher incidence in treated female rats than in controls. A mild nephrosis characterized by focal vacuolization of the renal tubular epithelium was observed in an increased incidence in treated mice. No significant increase in tumour incidence was observed in any of the treated groups in comparison with the corresponding controls. Survival of rats and mice given propyl gallate was similar to that of the controls. Mean body weights were lower in chemically exposed animals, and more so for females. Male rats exposed to propyl gallate showed an increased incidence of hepatic cytoplasmic vacuolization and suppurative inflammation of the prostate gland. Tumours of the preputial gland, islet-cell tumours of the pancreas, and phaeochromocytoma of the adrenal gland occurred at a significantly (P less than 0.05) higher incidence in the low-dose male rats. Malignant lymphoma occurred with a positive trend in male mice (control 1/50, low dose 3/49 and high dose 8/50), and the incidence in the high dose group was significantly (P less than 0.05) higher than in the control group. However, since the incidence in the control group was much less than the historical control rate (36/398 or 9%) in this laboratory, this apparent increase was not considered to be related to propyl gallate administration. Under the conditions of these studies, neither D-mannitol nor propyl gallate was considered to be carcinogenic to F344 rats or B6C3F1 mice of either sex. PMID- 3100404 TI - Effects of single-dose and repeated-dose pretreatment with 2(3)-tert-butyl-4 hydroxyanisole (BHA) on the hepatobiliary disposition and covalent binding to DNA of aflatoxin B1 in the rat. AB - The effects of two distinctive BHA pretreatment regimens on the biliary excretion of aflatoxin B1 (AFB) metabolites and the covalent binding of AFB to hepatic DNA were studied in vivo in the rat. To differentiate between enzyme induction effects and direct antioxidant effects, BHA was given to rats for 9 days (500 mg/kg/day, sc) or as a single dose (500 mg/kg, po), and [3H]AFB was administered ip. Repeated treatment with BHA enhanced the biliary excretion of both the glutathione conjugate of AFB and the AFP1-glucuronide to 200% of control values, reduced the amount of AFB remaining in the liver to 53% of control and reduced the covalent binding of AFB to hepatic DNA to 16% of control. A single BHA treatment had no effect on the biliary excretion of AFB or the binding of AFB to hepatic macromolecules, even though high concentrations of BHA were present in the liver during the period of AFB metabolism. These results support the hypothesis that BHA inhibits AFB carcinogenesis via the induction of phase II biotransformation pathways such as glutathione S-transferase, which act to reduce the amount of AFB-epoxide available for binding to DNA. We found no evidence of a direct antioxidant effect of BHA in altering the hepatobiliary disposition of AFB. PMID- 3100406 TI - Hydroxychavicol: a new phenolic antimutagen from betel leaf. AB - The phenolic compounds eugenol and hydroxychavicol were separated from betel leaf extract using C18 phase bonded Hiflosil silica gel. The structures of the two compounds were confirmed by nuclear magnetic resonance data. Neither eugenol nor hydroxychavicol was mutagenic when tested in various strains of Salmonella typhimurium with or without metabolic activation. Both compounds exhibited dose dependent suppression of dimethylbenzanthracene-induced mutagenesis in S. typhimurium strain TA98 with metabolic activation. Hydroxychavicol was more potent than eugenol in this respect. PMID- 3100403 TI - Gastric and oesophageal carcinogenesis: models for the identification of risk and protective factors. AB - Male weanling rats of the Charles River Sprague-Dawley strain were exposed to N methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the water for 3 months at the concentration of 75 ml/litre. Other real or potential risk factors were administered, alone or in combination with MNNG. When MNNG was administered in combination with NaCl, bile acids, aspirin or BHA, forestomach tumours were enhanced. MNNG-induced tumours were inhibited by selenium or by difluoromethylornithine, an ornithine decarboxylase inhibitor. BHA alone caused forestomach tumours. When BHA was administered by dietary means or by gavage, alone or in combination with MNNG, the gavage method resulted in greater tumorigenesis than dietary exposure. This increase was associated with increased [3H]thymidine labelling of forestomach epithelium and increased hyperplasia. Oesophageal carcinogenesis induced by methylbenzylnitrosamine (MBN) was enhanced by zinc deficiency, alcohol and 13-cis-retinoic acid. Zinc deficiency also resulted in oesophageal tumours in rats exposed to the hepatocarcinogen dimethylnitrosamine. Riboflavin deficiency injured oral and oesophageal epithelium and increased sensitivity to MBN-induced oesophageal tumours. PMID- 3100407 TI - [Increasing active immunity in chronic recurring tonsillitis]. PMID- 3100405 TI - Disposition of sucrose octa-isobutyrate in rats, dogs and monkeys. AB - The disposition of 200 mg/kg of 14C-labelled sucrose octa-isobutyrate (14C-SOIB), a component of sucrose acetate isobutyrate (SAIB), a beverage emulsion stabilizer, was studied in rats, dogs and monkeys. After oral administration of 14C-SOIB to three rats, 3-15% of the dose was excreted as volatile products, 1-2% appeared in urine and 78-93% was recovered in faeces. In dogs, recoveries of radiolabel in CO2, urine and faeces were approximately 1%, less than 2% and 77 94%, respectively. Monkeys excreted the majority of the dose in faeces; less than 2% of the administered radioactivity was eliminated in either CO2 or urine. The biliary excretion of radiolabel from 14C-SOIB was negligible in rats and monkeys; however, in dogs, 3-10% of the dose was excreted into bile. It was demonstrated by chromatographic analyses of faeces that 14C-SOIB was more extensively hydrolysed in the gastro-intestinal tract of rats and dogs than in monkeys. The results indicate that after oral administration, rats and dogs absorb SOIB following hydrolysis of the sugar ester in the gut. The proportion of the dose that is absorbed by the rat is oxidized to CO2. In the dog, little of the absorbed product is oxidized; rather, it is circulated through an enterohepatic pathway. In contrast, in the monkey, SOIB is not detectably hydrolysed in the gut or absorbed. These findings show that there is a species difference in the disposition of SOIB; the most salient findings relate to a difference in the disposition of SOIB in the dog compared with the rat. PMID- 3100408 TI - [Clinical experiences with misoprostol]. PMID- 3100409 TI - [Experimental study on adequate composition of glucose, protein and fat in puppies with liver dysfunction during parenteral nutrition]. PMID- 3100410 TI - Virological significance of HBeAg subtypes (HBeAg/1 and HBeAg/2) in patients with type B hepatitis. AB - In order to establish the virological significance of HBeAg subtypes (HBeAg/1 and HBeAg/2) during hepatitis B virus infection, HBsAg, HBeAg and hepatitis B virus DNA in serum and HBcAg in liver were determined quantitatively in relation to the detection of HBeAg subtypes in agar gel diffusion. Thirty-eight chronic HBsAg carriers with HBeAg, including 16 non-specific reactive hepatitis, 8 chronic persistent hepatitis, 11 chronic active hepatitis and 3 liver cirrhosis, who were seen at Tohoku University Hospital from 1983 to 1985, were examined. Significantly larger amounts of HBsAg, HBeAg and hepatitis B virus DNA in serum and HBcAg in liver were found in patients positive for both HBeAg/1 and HBeAg/2 in serum than in those positive for only HBeAg/1 or negative for both subtypes. These results suggest that the presence of HBeAg/2 in serum may reflect the occurrence of active viral replication. When the detection pattern of HBeAg subtypes was examined during serial follow-up for at least 1 year, three groups of patients were classified with respect to the presence of HBeAg/2, i.e., Type I, consistently positive for HBeAg/2; Type II, consistently negative for HBeAg/2, and Type III, intermittently positive for HBeAg/2. More than 80% of Type I patients were histologically diagnosed having as nonspecific reactive hepatitis, while more than 80% of Type II and III patients had more progressive liver diseases such as chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis. These results suggest that the serial examination of HBeAg subtypes in serum may be important for more detailed evaluations of type B hepatitis. PMID- 3100411 TI - Staining for factor VIII related antigen and Ulex europaeus agglutinin I (UEA-I) in 230 tumours. An assessment of their specificity for angiosarcoma and Kaposi's sarcoma. AB - In this study we examined the staining reactivity of commercially available antisera to factor VIII related antigen (F VIII RAg) and Ulex europaeus agglutinin I (UEA-I) on sections from 230 formalin fixed paraffin embedded tumours. These included 196 sarcomas, 20 carcinomas and 14 angiomas. All angiomas showed positive staining for F VIII RAg; all carcinomas showed negative staining; the vasoformative areas of all angiosarcomas stained positively but only four of six angiosarcomas showed positive staining of their solid areas; of seven Kaposi's sarcomas, all showed positive staining of vessels and six showed positive staining of the spindle cell component. In the remaining 181 non vascular sarcomas there was a false positive result in four tumours (2.2%), three of which had a history of irradiation. Pre-radiotherapy biopsies of these three tumours stained negatively with anti-F VIII RAg. UEA-I was demonstrated in all the angiomas studied, in all angiosarcomas (including the solid components) and in well-formed vessels of all Kaposi's sarcomas, but only in the spindle cell component of 3/6. However, there was an unacceptably high rate of false positive staining amongst the carcinomas and non-vascular sarcomas. In conclusion, F VIII RAg is a specific but not a sensitive marker of angiosarcomas; UEA-I is a sensitive but not a specific marker of angiosarcomas. PMID- 3100413 TI - Assessing outcome. PMID- 3100414 TI - Ambulatory care payment system ready, waiting. PMID- 3100415 TI - Landmark U.S. health survey hits the field. PMID- 3100412 TI - A comparison of cytoplasmic immunoglobulins in retroperitoneal fibrosis and abdominal aortic aneurysms. AB - Retroperitoneal fibrosis is associated with Riedel's thyroiditis, in which an unexpectedly high proportion of the plasma cells have been reported to contain IgA and lambda light chains. It has been suggested that retroperitoneal fibrosis and the inflammation and fibrosis in thick-walled abdominal aortic aneurysms are caused by a hypersensitivity reaction to antigens leaked from aortic atheroma. We examined cases of retroperitoneal fibrosis and aortic aneurysms in order to quantify the types of heavy and light chains in the plasma cells. A mean of 44% of the plasma cells contained IgA and 52% contained lambda light chain. These results provide further evidence of the pathological relationship between retroperitoneal fibrosis and Riedel's thyroiditis. It is suggested that a cross reaction between antigens in mucosal surfaces and in the thyroid or retroperitoneum may be implicated, possibly involving vessel walls. Of the total plasma cells in the wall of the aortic aneurysms 24% contained IgA and 40% lambda, although there was a significant trend towards a higher proportion of IgA with increasing thickness of the wall. No definite support for a relationship between atheroma and retroperitoneal fibrosis is provided by this study. PMID- 3100416 TI - von Willebrand disease. AB - von Willebrand disease (vWD) is a bleeding disorder characterized by a complex hemostatic defect. Abnormal platelet function, usually reflected by a prolonged bleeding time, is the result of a quantitative or qualitative defect of von Willebrand factor (vWF). A secondary deficiency of factor VIII procoagulant protein (factor VIII) may occur leading to a coagulation defect as well. These two glycoprotein macromolecules circulate as a complex in plasma. This article will review current understanding of structures and functions of vWF factor and factor VIII as they relate to the pathogenesis, diagnosis, classification and therapy of vWD. PMID- 3100417 TI - Molecular pathology and immunology of factor VIII (hemophilia A and factor VIII inhibitors). AB - Factor VIII is a large procoagulant glycoprotein that circulates in plasma in a noncovalent complex with von Willebrand factor. It is essential for the efficient cleavage of coagulation factor X by factor IXa, and its absence causes a severe bleeding disorder. Plasma factor VIII is reduced from the normal range of approximately 100 to 200 ng/ml in patients with the hereditary coagulation defect, hemophilia A, as well as in patients who develop autoantibodies that inactivate factor VIII. The understanding of factor VIII structure has been enhanced by recent studies that have characterized the X chromosome gene responsible for its synthesis, and preliminary information is now available about specific genetic defects. The basis for antibody formation in approximately 15 per cent of repeatedly transfused hemophilic patients is less clear at this time, however, for these individuals appear to have a variety of genetic defects that are not characteristically different from the patients who do not develop inhibitors. Although the antibodies cause a serious problem for affected individuals, they have been very useful in characterizing normal factor VIII and nonfunctional factor VIII-like protein that is found in the plasmas of 10 per cent of patients with mild hemophilia. Moreover, they are very useful reagents that can be used for immunoassay of factor VIII that has been modified in ways that have destroyed its procoagulant function. PMID- 3100418 TI - Synergistic effect of aphidicolin and ethanol on the induction of common fragile sites. AB - The effect of ethanol on the frequency of aphidicolin-induced common fragile sites was studied using lymphocyte cultures from two normal women. Aphidicolin was added to the cultures at a final concentration of 0.2 microM and ethanol at 0.02%, 0.1%, 0.2%, 0.5%, and 1%, both during the last 26 h of culture. The frequency of common fragile sites increased from 296% in subject 1 and 201% in subject 2 with aphidicolin plus 0.02% ethanol, to 765% and 823%, respectively, with aphidicolin plus 1% ethanol. Ethanol alone added to cultures did not induce common fragile sites. The gaps and breaks induced by aphidicolin plus ethanol were highly nonrandom. Altogether, 35 common fragile sites were identified. The addition of 1% ethanol to aphidicolin increased both random and nonrandom gaps and breaks as compared with that of 0.02% ethanol. Dimethyl sulfoxide added to culture at final concentrations of 0.02% to 1% did not change the frequency of aphidicolin-induced fragile sites. The frequency of fluorodeoxyuridine-induced fragile sites was not affected by the addition of 0.02% to 1% ethanol. It was thus concluded that ethanol enhances the aphidicolin-induced fragile sites, possibly inhibiting the repair mechanism of gaps and breaks induced by aphidicolin. PMID- 3100419 TI - Blood lactate and ketone body concentrations in salicylate intoxication. AB - Blood concentrations of lactate, ketone bodies and non-esterified (free) fatty acids were measured in 45 adult patients on admission to the poisoning treatment centre, with salicylate and mixed salicylate-sedative/ethanol poisoning. Nine patients had blood lactate concentrations above 2 mmol/l and six patients had ketone-body concentrations greater than 1 mmol/l. Eight of the nine patients with hyperlactacidaemia had mixed salicylate/ethanol or sedative poisoning, whereas four of the six patients with hyperketonaemia had pure salicylate poisoning. No direct correlation was found between the presence of these metabolic disturbances and the severity of poisoning. Since only one patient was found with organic acid concentration in the blood exceeding 5 mmol/l, it is concluded that concomitant endogenous acidosis rarely contributes to the acid-base disturbance seen in salicylate poisoning in adults. PMID- 3100421 TI - Generation of a new monoclonal antibody and its application for determination and purification of biologically active human gamma-interferon. AB - Three monoclonal antibodies (MAbs) were raised against recombinant human gamma interferon (rHuIFN-gamma). They were specific for rHuIFN-gamma and recognized parts of the molecule other than both terminal regions. Among these MAbs, only KM48 has an ability to neutralize the antiviral activity of rHuIFN-gamma. Using KM48 in combination with polyclonal antibodies, we have developed a double sandwich enzyme immunoassay (ELISA). This ELISA preferentially detects the biologically active form of rHuIFN-gamma, because after treatment with 1 N HCl or 0.2% SDS, or at 95 degrees C, the reactivity in the ELISA and the biological activity determined by cytopathic effect (CPE) assay decrease in parallel. In addition, the ELISA recognizes both natural and rHuIFN-gamma with almost the same sensitivity. Therefore, the ELISA is useful for detecting the biologically active conformation of rHuIFN-gamma, and possibly may be useful in both industrial production and clinical studies. rHuIFN-gamma molecules bind specifically to the immunoaffinity column using the MAb KM48 as ligands. After elution with 7 M Urea/1 M NaCl, the rHuIFN-gamma can be renatured in phosphate-buffered saline with high recovery. Thus, the column provides simple one-step purification of biologically active rHuIFN-gamma. PMID- 3100420 TI - Differential susceptibility to modulation by recombinant immune interferon of HLA DR and -DQ antigens synthesized by melanoma COLO 38 cells. AB - Recombinant immune interferon (IFN-gamma) induced a dose-related increase in the synthesis and expression of HLA class II antigens by the cultured melanoma cells COLO 38. Although IFN-gamma-treated melanoma cells COLO 38 continue to express higher levels of HLA-DR antigens than of HLA-DQ antigens, the effect of IFN-gamma was more marked on HLA-DQ antigens than on HLA-DR antigens, as indicated by the dose and incubation time required to induce the changes and by the extent and duration of the increase. The effect of IFN-gamma on HLA class II antigens is significantly higher than that of leukocyte and fibroblast interferons. Analysis by one- and two-dimensional gel electrophoresis of antigens synthesized by melanoma cells COLO 38 in the presence of IFN-gamma did not detect any significant change in the structural profile of the subunits of HLA-DR and -DQ antigens. PMID- 3100422 TI - Modification of emerging repertoires by immunosuppression in immunodeficient mice results in autoimmunity. PMID- 3100423 TI - [Septic disease pictures in Salmonella infections]. AB - 3715 strains of salmonella have been isolated from various sources from 1976 to 1985. 26 of these isolates have been S. typhi and paratyphi B, 3689 isolates were nontyphoid strains. 7 isolates of S. typhi and S. paratyphi have been isolated from blood cultures. All persons infected with these strains have acquired these organisms in tropical and subtropical areas. In contrast, salmonella gastroenteritis is mainly confined to the intestinal tract. 21 isolates of nontyphoid salmonellae, however, have been isolated from blood cultures. The vast majority of these patients showed compromised host defense mechanisms. Newborn infants up to 3 months are considered particularly vulnerable for bloodstream invasion with nontyphoid salmonellae. Patients with chronic consuming disorders, solid tumors and haematologic malignancies, and the treatment of these ailments with immunosuppressive drugs and corticosteroids predisposes patients for extraintestinal spread of an enteric salmonella infection. Corticosteroid therapy seems to be particularly responsible for a fulminant course of the disease and poor outcome of the infection. PMID- 3100424 TI - [In vitro activity of ciprofloxacin and ofloxacin against Mycobacterium tuberculosis, M. avium, M. africanum, M. kansasii and BCG strains]. AB - The in vitro activity of ciprofloxacin and ofloxacin against 33 strains of mycobacteria was investigated in a comparative study. The resulting MIC values were compared with serum levels, measured in a cross-over study. Possible therapeutic application of these substances in mycobacterial infections are being discussed. We found the antimycobacterial activity of ciprofloxacin to be insufficient for its clinical application, whereas the corresponding MIC values for ofloxacin could be achieved in vivo. Further animal and clinical studies appear justified. PMID- 3100425 TI - [Imipenem resistance in Pseudomonas aeruginosa]. AB - Mutants of P. aeruginosa resistant to imipenem can be selected at high frequency in vitro. They remain susceptible to other beta-lactams. Strains resistant both against imipenem and other beta-lactams are, however, detectable in vitro and in vivo. Imipenem-resistant strains appeared in blood cultures and emergence of IMI resistance during therapy has been observed. The activity of other beta-lactams against P. aeruginosa is antagonized in the presence of IMI, because of beta lactamase induction by imipenem. In addition to the risk of emergence of IMI resistance of P. aeruginosa during therapy, there is an increasing incidence of IMI-resistant strains already existing prior to therapy. In the treatment of infections caused by P. aeruginosa combination therapy including a non-beta lactam antibiotic active against the pathogen is indicated. PMID- 3100426 TI - [Development of resistance in imipenem therapy in Pseudomonas aeruginosa]. AB - 8.4% of the isolated Pseudomonas aeruginosa strains were resistant against imipenem in this study. 3.7% of them became resistant as a result of the antibiotic therapy. In some patients on intensive care units, the resistance of Pseudomonas aeruginosa against imipenem emerged within a few days. In two of these cases a simultaneous loss of activity of the other pseudomonas-beta-lactams was observed. PMID- 3100427 TI - [Characterization of imipenem resistance in Pseudomonas aeruginosa: decreased phenotypic expression of outer membrane proteins D1 and D2]. AB - Imipenem-resistant variants can be selected from clinical Pseudomonas aeruginosa isolates in a frequency of 10(-8) to 10(-7) and 10(-5) in a single strain. In any case, there was no cross resistance between imipenem and other beta-lactams. In all IMI variants the induction potency of imipenem for the chromosomally-mediated Id beta-lactamase was markedly diminished as compared to the corresponding parent strains. Moreover, in all imipenem-resistant variants as well as in imipenem resistant clinical isolates phenotypic expression of either a 46,000 dalton or a 47,000 dalton outer membrane protein was marginal; these proteins could be identified as proteins D1 and D2. These findings suggest a penetration barrier responsible for imipenem-resistance in Pseudomonas aeruginosa. PMID- 3100428 TI - [Treatment of bronchopulmonary infections in patients during artificial respiration with imipenem/cilastatin]. AB - In an open prospective study the efficacy and tolerance of imipenem/cilastatin was investigated in 24 critically ill patients on mechanical ventilation with nosocomial respiratory tract infection. Nine patients had previously received antibiotic therapy which had failed. Imipenem was given in a dose of 1-3g/24 h over 5-37 (mean 11) days. Seven patients were additionally treated with aminoglycosides, one patient with erythromycin. Pseudomonas aeruginosa, Staphylococcus aureus, Hemophilus influenzae and Escherichia coli were the most frequently isolated pathogens from tracheobronchial secretions. 91% of the infections without and 77% with involvement of Pseudomonas aeruginosa were successfully treated. All of the gram-positive and 85% of the gram-negative pathogens (Pseudomonas not included) were eliminated in the course of therapy. By contrast, 64% of the isolates of Pseudomonas aeruginosa persisted; half of these became imipenem-resistant. Nine patients showed adverse reactions including one case of pseudomembranous colitis which were reversible. Imipenem/cilastatin proved highly effective and was relatively well tolerated; limitations in the efficacy were seen in cases of infection due to Pseudomonas aeruginosa. PMID- 3100429 TI - [Selection of resistant variants by broad spectrum beta-lactam antibiotics: to what extent is there cross resistance between imipenem and other beta-lactam antibiotics?]. AB - Resistant variants can be selected in the presence of most of the recently developed beta-lactam antibiotics thus resulting in cross resistance between penicillin-, cephalosporin- and monocyclic derivatives except for imipenem. Among the Enterobacteriaceae-resistant so-called beta-lactamase-overproducing variants can be selected in some species in the presence of various broad-spectrum beta lactams except for imipenem. However, imipenem-resistant variants can be selected from clinical Pseudomonas aeruginosa isolates in a frequency comparable to those obtained for other beta-lactams. Imipenem resistance in Pseudomonas aeruginosa is presently understood to be independent of either enzymatic degradation or an alteration of the penicillin-binding proteins; moreover, it has to be attributed to characteristic changes of the outer membrane proteins, thus explaining imipenem resistance due to impaired penetration. Consequently, resistance to imipenem in Pseudomonas aeruginosa has to be considered independent of resistance to other beta-lactams. PMID- 3100430 TI - Biological aspects of tumor necrosis factor. AB - Tumor necrosis factor (TNF) has been determined as an endogenous mediator for endotoxin-induced tumor necrosis. This macrophage product has been biochemically characterized and its protein structure defined by molecular cloning of the TNF gene. Experiments with antibodies to TNF demonstrated that TNF acts as an effector molecule of activated cytotoxic macrophages involved in tumor destruction. Purified TNF has been shown to exert direct necrotic activity against tumors in vivo. In addition, a number of similar effects in vivo and in vitro of TNF, endotoxin, and interleukin 1 (IL 1) have been observed. For example, in vivo the thermoregulatory activity of TNF is similar to IL 1. Since TNF was found to mediate other effects of endotoxin in modulating immune responses in addition to the tumor necrotic activity, it can be considered a true immunoregulator produced by macrophages after endotoxin stimulation. PMID- 3100431 TI - Multiple biological properties of recombinant human interleukin 1 (beta). PMID- 3100432 TI - Characterization of the human interleukin 2 receptor at the DNA, RNA, and protein level. PMID- 3100433 TI - Specific immunosuppressive therapy by monoclonal anti-IL 2 receptor antibody and its synergistic action with cyclosporin. AB - The effects of anti-IL 2R mab treatment on local GVHR and on heterotopic cardiac allograft survival in rats were investigated. Anti IL 2 mab inhibited specifically both GVHR as well as allograft rejection. IL 2R-targeted therapy was superior to that of anti-T helper/inducer cell treatment, as it did not affect T subset distribution and did not reduce the number of circulating T lymphocytes. This therapy when combined with a low subtherapeutic dose of CsA exerted a strongly synergistic effect. The results support the concept of IL 2R-targeted therapy in suppressing undesired immune reactions with limited side effects. PMID- 3100434 TI - Human interleukin 2: molecular biology, physiology and clinical possibilities. PMID- 3100435 TI - Results of clinical trials with the administration of interleukin 2 and adoptive immunotherapy with activated cells in patients with cancer. AB - The administration of transferred lymphokine-activated killer (LAK) cells in conjunction with the administration of recombinant interleukin 2 (IL 2) at high doses has led to objective remissions in 14/41 cancer patients. Sequential studies with both Jurkat-derived IL 2, recombinant IL 2 and activated cells were conducted in a total of sixty-seven patients with cancer which established the safety, toxicity and immunologic effects of these treatments prior to their successful combination in humans. This regimen was developed in pulmonary and hepatic metastases models in mice using a variety of transplantable tumors. More recently we have demonstrated both in mice and in patients with melanoma that very high doses of recombinant IL 2 (greater than 100,000 units/kg administered three times daily) can lead to objective regressions. The future development of these immunotherapies will include their evaluation in adjuvant settings as well as in combination with other conventional cancer treatments. PMID- 3100436 TI - Intralymphatic interleukin 2 treatment in patients with acquired immunodeficiency syndrome: preliminary experience in three cases. AB - Patients with opportunistic infections during the course of acquired immunodeficiency syndrome (AIDS) were analyzed for cellular immune functions and found to be severely immunocompromised. In particular, interleukin 2 (IL 2) production appeared to be defect not only qualitatively but also quantitatively. In some of these patients, exogenous IL 2 improved immune response in vitro. Intralymphatically administered highly purified natural IL 2 was given repeatedly (over a time period of ten days) to three of these patients. In two cases, such a treatment course was repeated later. Clinical response - at least in some patients - appeared to be of temporary benefit. Shortly after termination of IL 2 application in two patients an increase of lectin responsiveness as well as improved reactivity in skin testing was noted, encouraging further exploration of IL 2 as an immunostimulatory drug in AIDS patients. PMID- 3100437 TI - Dendritic cells and the initiation of contact sensitivity to fluorescein isothiocyanate. AB - Lymph node cells taken 24 hr after skin-painting mice with the contact sensitizer fluorescein isothiocyanate (FITC) induce delayed-type hypersensitivity in recipient mice. Skin-painting increased the number of dendritic cells (DC) in the draining lymph nodes without significantly changing the number of lymphocytes at 24 hr. The antigen was preferentially located on the DC. Raising the dose of FITC increased both the number of DC and the amount per cell. The addition of these DC to syngeneic lymph node cells at a ratio as low as 1:300 initiated proliferative responses in vitro. The level of proliferation was related to the amount of antigen on the DC. Mice given 50,000 of these fluorescent DC developed specific contact sensitivity reactions. DC exposed in vitro to FITC also acquired antigen and were able to initiate proliferative responses in vitro and to sensitize recipient mice. The DC may therefore be the prime cell involved in the induction of delayed-type hypersensitivity. PMID- 3100439 TI - Increased interleukin-2 receptor expression after mitogen stimulation on CD4- and CD8-positive lymphocytes and decreased interleukin-2 production in HTLV-III antibody-positive symptomatic individuals. AB - We investigated the expression of the interleukin-2 (IL-2) receptor on phytohaemagglutin-stimulated peripheral blood lymphocytes from homosexual men with persistent generalized lymphadenopathy, the prodrome of the acquired immune deficiency syndrome. The subjects were positive for antibody against human T-cell lymphotropic virus III. Using two-colour fluorescence flow cytometry, IL-2 receptor expression was determined on both the CD4- and CD8-positive lymphocyte subpopulations. After 48 hr of stimulation, expression of the IL-2 receptor on both T-cell subsets was significantly increased in lymphadenopathy patients as compared to values in heterosexual age-matched controls; this difference was less after 72 hr of stimulation. Results from two AIDS patients were within the normal range. IL-2 production was significantly reduced in both lymphadenopathy and AIDS patients as compared to values in heterosexual controls. We conclude that a defect in IL-2 production is associated with human T-cell lymphotropic virus III infection, but that the expression of the IL-2 receptor on T cells is not greatly affected. PMID- 3100438 TI - Polymorphism for RhT3, a CD3-like cell surface antigen, expressed on rhesus monkey T lymphocytes. AB - The target antigen of the FN18 monoclonal antibody, called RhT3, is probably the rhesus monkey homologue of the human CD3 antigen, expressed on mature T cells. RhT3 appears to be polymorphic, since FN18 was not reactive with T cells from all the screened animals. Thus, immunofluorescent staining of peripheral blood lymphocytes with FN18 antibody revealed either a positive or a negative phenotype for the target antigen. In a rhesus monkey population, nonreactivity for FN18 was observed in low frequency (2.7%). Expression and non-expression of RhT3 appeared to be constant characteristics. Non-expression was not associated with any demonstrable immunodeficiency. Further, there seemed to be no association between the presence of the FN18 target antigen and sex, age or expression of MHC class I antigens. Family studies indicated that the positive phenotype is expressed in the same fashion by animals presumably heterozygous or homozygous for the positive allele, the negative phenotype being expressed only on cells from animals homozygous for an assumed blank allele. Therefore, the positive phenotype is likely to be transmitted in an autosomal dominant mode. In the animals with the negative phenotype, normal T-cell numbers were present, as was demonstrated by B- and T-cell specific monoclonal antibodies. Cytoplasmic staining of cytospun lymphocyte preparations with FN18 revealed that polymorphism was present at the intracellular level. Cell proliferation tests, using PWM and Con A as mitogens, showed the presence of apparently functional RhT3 cell surface molecules in FN18 non-reactive animals. Polymorphism is therefore assumed to be at the epitope level. PMID- 3100440 TI - T-cell independent transfer of organized granuloma formation. AB - A direct role for delayed hypersensitivity in organized granuloma formation has been emphasized in the literature, but some clinical and experimental studies have suggested a more complicated relationship. In order to further evaluate T cell function in cutaneous granulomatous inflammation, hepatic granulomas isolated from athymic mice with schistosomiasis were grafted into the skin of athymic and euthymic mice. Granulomas developed in athymic mice, as seen previously after transplantation of euthymic hepatic granulomas, indicating that granulomas develop in the skin without T-cell function. However, the granulomas in athymic mice skin were smaller and lacked eosinophils and mast cells, whereas the athymic mouse granulomas grafted in euthymic mice skin were larger, better organized, and associated with tissue eosinophilia. These findings suggest that granuloma initiation itself is T-cell independent, but that T-cell participation enhances the granulomatous reaction. PMID- 3100441 TI - Study on the pre-haemolytic complex formed upon polyethylene glycol-induced activation of mouse complement. AB - The stability and nature of haemolytic activity generated in normal mouse serum upon precipitation with a critical amount of polyethylene glycol and incubation of the redissolved precipitate in the presence of 10 mM EDTA were investigated. The activity appeared to be stable at 0 degrees C which enabled further analysis. The haemolytic mixture was subfractionated by repeated differential polyethylene glycol precipitation yielding two preparations with little or no haemolytic activity by themselves, but which regained activity upon recombination. Material precipitating between 4 and 9% polyethylene glycol became haemolytic when combined with C5-deficient serum. The ultracentrifugation profile of this subfraction strongly suggested the presence of C56-complexes. PMID- 3100442 TI - Lymphocyte activation by the Fc region of immunoglobulins. AB - The Fc region of Ig is required for numerous biological effector functions which include: opsonization, anaphylaxis, C fixation, catabolism of the Ig molecule, FcR binding, and immune regulation. To this latter point, the cellular and subcellular events involved in immune regulation by IC and Fc fragments of Ig have been the focus of numerous investigations. Characterization of cyanogen bromide cleavage fragments from a human IgG1 myeloma protein indicates that one biologically-active site is found in residues 335-357 of the CH3 domain of the molecule. Synthesis of the biologically-active region resulted in a peptide, termed p23, which stimulates mouse and human B cells to secrete polyclonal Ig and activates AA metabolic pathways. In contrast to these findings, p23 is unable to induce B cell proliferation or IL-1 secretion from macrophages. Analysis of data obtained with overlapping peptides, based on p23, suggests that the minimal active sequence needed for B cell differentiation is leu-pro-pro-ser-arg (residues 351-355). In contrast, only p23 or p23 minus the carboxyterminal glu356 and glu357 were able to induce PGE release. Release of biologically-active peptides derived from the Fc region of Ig into the cellular microenvironment may form the nucleus of a nonspecific in vivo immunoregulatory network. The specificity of peptide regulatory activities could reside in their effectiveness at high concentrations in the cellular microenvironment. The interaction of Fc region peptides with receptors on B cells, T cells, and macrophages/monocytes could result in a dynamic control of immune reactivity. PMID- 3100443 TI - Small bowel function in mild to moderate protein-energy malnutrition. PMID- 3100444 TI - Congenital diverticulum and valve obstruction of anterior urethra. PMID- 3100445 TI - Supplementary nutrition programmes for mothers and children in Himachal Pradesh. PMID- 3100446 TI - [Experiences with L-carnitine in the post-stress phase]. AB - A prospective randomized double blind investigation was made in 24 multiple injured patients. All patients were treated with a combined parenteral-enteral nutrition during 7 days. A group of 11 patients received as a continuous infusion over 16 h 60 mg/kg BW carnitine daily. Beside carnitine and acetylcarnitine levels in plasma and urine the following parameters were determinated to evaluate the effect of carnitine: for the metabolism of fatty acids: triglycerides, free fatty acids (FFA), alpha-hydroxy-butyrate for the metabolism of carbohydrates: glucose, insulin and lactate in plasma. Finally for amino acid metabolism: urea, creatinine, cholinesterase and kolloid osmotic pressure in plasma as well as ureanitrogen and alpha-aminonitrogen excretion in urine. In the patients receiving carnitine especially acetyl-carnitine in plasma and acetyl-carnitine excretion in urine increased, proving that the administered carnitine can pass through the mitochondrial membrane. In these patients the plasma level of FFA was markedly lower than in the group without carnitine. Simultaneously the level of the alpha-hydroxybutyrate was elevated, equivalent to an increased oxydation of fatty acids. There was no difference between the two groups in the metabolism of carbohydrates. Administration of carnitine caused a slight increase of the production of urea (PU), catabolism could not be reduced. The excretion of alpha aminonitrogen in urine augmented after carnitine infusion. Carnitine is an AA itself and so the amount of excreted alpha-amino nitrogen will increase; additionally the reabsorption of AA in the proximal renal tubulus may be inhibited by carnitine. PMID- 3100447 TI - Differentiation and interaction of secretory immunoglobulin A and a calcium dependent parotid agglutinin for several bacterial strains. AB - Previous studies have suggested that both secretory immunoglobulin A (sIgA) and various nonimmunoglobulin salivary glycoproteins are capable of agglutinating a variety of bacteria. The present study was designed to compare the nature of the agglutinins for Streptococcus mutans and Salmonella typhimurium in parotid saliva and colostrum. S. mutans was aggregated by saliva and colostrum, whereas S. typhimurium was aggregated only by saliva as detected by a spectrophotometric method. The principal salivary agglutinin for both S. mutans and S. typhimurium was calcium dependent and could be desorbed in phosphate-buffered saline (pH 6.8). In contrast, the colostral agglutinin was calcium independent and not readily desorbed. The agglutinin activities of saliva and colostrum for S. mutans were additive, suggesting independent target sites on the bacterial surface. The agglutinin activity of colostrum was totally associated with sIgA as was suggested by blocking of the agglutinating activity with anti-alpha-chain serum and the absence of blocking with an antibody specific for salivary agglutinin. Interestingly, anti-alpha-chain serum removed all agglutinating activity from saliva, but not from the phosphate-buffered saline-desorbed agglutinin. Dialysis of parotid saliva against 0.1 M disodium EDTA eliminated the agglutinin blocking activity of anti-alpha-chain serum but not that of the antiagglutinin antibody. The ability of anti-alpha-chain serum to block agglutination of the EDTA-dialyzed saliva could be restored by the addition of calcium chloride, suggesting that sIgA and salivary agglutinin are associated through a calcium-mediated interaction. These results indicate that bacterial agglutinating activity of colostrum, as detected spectrophotometrically, is mediated by sIgA, and that of saliva is mainly dependent upon a calcium-dependent nonimmunoglobulin agglutinin. The agglutinating activities of sIgA and parotid agglutinin seem to be additive, and their calcium-dependent association may favor the enhancement of their respective activities. PMID- 3100448 TI - Induction of murine gamma interferon production by lipopolysaccharide and interleukin-2 in Propionibacterium acnes-induced peritoneal exudate cells. AB - Lipopolysaccharide (LPS) induces high levels of gamma interferon (IFN-gamma) in the circulation of mice pretreated with heat-killed Propionibacterium acnes. The following results were obtained in the present study. LPS, as well as interleukin 2 (IL-2), was also able to induce IFN-gamma in vitro in peritoneal exudate cells (PEC) from such mice. Splenocytes and lymph node cells from these mice or resident peritoneal cells from control mice produced trace or undetectable amount of IFN-gamma upon exposure to LPS. A synergistic effect on IFN-gamma induction was observed when LPS was added to a culture of PEC together with IL-2. Indomethacin augmented the induction of IFN-gamma by LPS or IL-2, and prostaglandin E2 reversed its effect. Deprivation of plastic-adherent or nylon wool-adherent cells abolished the induction by LPS or IL-2, whereas it did not affect that by concanavalin A. Culture supernatant of plastic-adherent cells incubated with LPS stimulated the nylon wool-nonadherent cells to produce IFN gamma in the presence of IL-2, but interleukin-1 or phorbol myristic acetate did not replace the LPS-stimulated supernatant. The ability of PEC to produce IFN gamma measured as a function of time after P. acnes injection increased in proportion to their natural killer (NK)-like activity against YAC-1 cells. Moreover, treatment of PEC with monoclonal anti-Thy-1 antibody or with anti asialo GM1 antiserum plus complement eliminated the production of IFN-gamma and the NK-like activity simultaneously, whereas treatment with monoclonal anti-Lyt-2 antibody plus complement did not. These results suggest that IL-2 and some unidentified factor released from plastic-adherent cells by LPS stimulation cooperatively induce IFN-gamma production in activated, Thy-1- and asialo GM1 positive NK-like cells appearing in inflammatory reactions and that prostaglandin E2 regulates IFN-gamma production in these cells. PMID- 3100450 TI - Eosinophil chemotactic lymphokine produced by spleen cells of Schistosoma japonicum-infected mice. AB - Eosinophil chemotactic factor (ECF) was detected in the cell-free supernatant of the culture of spleen cells obtained from Schistosoma japonicum-infected mice. ECF production by spleen cells was dependent on both the amount of soluble egg antigen (SEA) added and the number of cells in the culture. When sufficient amount of SEA was added to the culture, ECF production was detectable by 6 h after incubation, reached a plateau by 24 h and then rapidly decreased. ECF was produced by nonadherent, Thy 1.2-positive cells, indicating that it is a lymphokine. After Sephadex G-75 gel chromatography, estimated molecular weight of this ECF was 15,000-20,000 daltons. When eosinophils were preincubated with this ECF lymphokine, their chemotactic reactivity to S. japonicum egg-derived ECF was significantly enhanced, although this pretreatment caused neither the deactivation of chemotactic reactivity to homologous ECF nor the enhancement of the random migration of eosinophils. Thus, this ECF lymphokine seems to be important not only as a chemoattractant but also as an activator of eosinophilotaxis around deposited eggs in schistosomiasis japonica. PMID- 3100451 TI - Comparison of arachidonic acid metabolism in nasal polyps and eosinophils. AB - Nasal polyp tissue is characterized by its frequent infiltration by large numbers of eosinophils. We have studied the metabolism of 14C-labeled arachidonic acid by both nasal polyp tissue and by eosinophils. The major metabolite produced by both is 15-hydroxyeicosatetraenoic acid (HETE) with lesser amounts of 12-HETE. No cyclooxygenase pathway products were found. The 15-lipoxygenase activity of nasal polyps averages 30 times that of normal nasal mucosa or chronically inflamed sinus mucosa. Nasal polyps which contained significant numbers of eosinophils averaged 7 times the 15-lipoxygenase activity of nasal polyps without eosinophilia. Thus, eosinophils appear to be a major source of 15-lipoxygenase activity in nasal polyps. PMID- 3100449 TI - Mycobacterium leprae-burdened macrophages are refractory to activation by gamma interferon. AB - Mycobacterium leprae grows to enormous numbers in the nu/nu mouse footpad, producing granulomas resembling those of lepromatous leprosy in humans. Footpad granuloma cells gorged with M. leprae were established in primary cell culture to examine their functional capabilities. These cells were classified as macrophages by the following criteria: positive staining for nonspecific esterase, reduction of Nitro Blue Tetrazolium during phagocytosis of Candida albicans, possession of Fc receptors, and possession of Mac-1 antigen. Footpad macrophages also phagocytized and supported the intracellular growth of Toxoplasma gondii. However, unlike peritoneal macrophages, footpad macrophages could not be activated to kill or inhibit T. gondii by macrophage-activating factor produced by mitogen-stimulated spleen cells or by recombinant gamma interferon. Thus, although the lepromatous macrophages appeared to be normal in many of their functions, they were defective in response to macrophage-activating signals. PMID- 3100452 TI - Immunopathology of experimental Schistosoma mansoni: immunohistochemical localization of parasite antigens in the host tissue. AB - Schistosoma mansoni antigens play a crucial role in the induction of immunopathological processes and in modulating the host immune system. A polyclonal rabbit antiserum to an antigenic fraction of adult schistosoma worms was used to localize worm and egg antigens in tissue sections of infected mice. Most granuloma formations identified in paraffin sections of portal tracts and intestinal mucosa were vigorous with florid cellular composition, consisting of macrophages and epithelioid cells, surrounding a central nidus of S. mansoni egg. Schistosome pigments were demonstrated at the periphery of the granuloma, within sinusoidal Kupffer's cells and within macrophages of intestinal mucosa. Large amounts of schistosome antigen were found sequestered in the mesenteric lymph nodes and in the spleen. A strong reaction for locally synthesized IgG was found. These findings suggest that the schistosome antigen-antibody complex found in the host lymphoreticular system plays a major role in the immunopathological process. PMID- 3100453 TI - Clonal analysis of T lymphocytes infiltrating the thyroid gland in Hashimoto's thyroiditis. AB - T cells isolated from thyroid tissue and peripheral blood of 2 patients with Hashimoto's thyroiditis were studied by a high cloning efficiency microculture technique. Clonal efficiencies of 37 and 24% were obtained from thyroid-derived T cell cultures, while 40 and 90% efficiencies resulted from peripheral-blood derived cultures. A prevalence of T4-/T8+ T cell clones were found in thyroid infiltrates. The functional analysis of the clones demonstrated significantly higher proportions of clones with cytolytic activity in a lectin-dependent assay in thyroid-derived microcultures, as compared to peripheral blood-derived ones. The proportion of clones displaying natural-killer-like activity was increased in 1 patient only. Cytolytic activity was displayed not only by all T4-/T8+, but also by several T4+/T8- intrathyroid clones. Remarkable proportions of cytolytic clones were also able to release interleukin-2 upon phytohemagglutinin stimulation. Finally, the proportion of T cell clones able to release gamma interferon following mitogen stimulation was significantly higher in thyroid- vs. peripheral-blood-derived microcultures. These results provide further data about the possible pathogenetical role of both regulatory and effector T lymphocytes in human autoimmune thyroiditis. PMID- 3100454 TI - Ionophore-stimulated rat basophilic leukemia cells produce PAF-acether. AB - Ionophore (A23187) stimulated rat basophilic leukemia (RBL-1) cells produce a lipid mediator which caused rabbit platelets to aggregate and which by using platelet-activating factor (PAF)-acether antagonists and high-pressure liquid chromotography was shown to be PAF-acether. Thus RBL-1 cells represent a cell type suitable for studying the coordinated release of three mediators of anaphylaxis: histamine, leukotrienes C4/D4 (slow-reacting substances) and PAF acether. PMID- 3100456 TI - The fate of acrosomal staining during the acrosome reaction of human spermatozoa as revealed by a monoclonal antibody and PNA-lectin. AB - A monoclonal anti-human sperm antibody, raised against an acrosomal antigen and indicated to recognize in boar sperm the serine protease, acrosin, stained in human spermatozoa a 50 Kd antigen and several others in the region 24-34 Kd by immunoblotting. The 50 Kd band and the region of 30-34 Kd showed proteolytic activity by zymographic enzyme detection. The fate of the antigen was studied in the acrosome reaction induced by the calcium ionophore A23187. In control incubations 69.5 +/- 14.2% (mean +/- SD) of the spermatozoa had intact acrosomal staining according to indirect immunofluorescence using this antibody whereas in acrosome-reacted samples only 21.0 +/- 2.0% of the sperm were stained. Another marker for the acrosome, peanut agglutinin-lectin (PNA), was used to detect the acrosome with similar results. Acrosome reactions were verified by electron microscopy. The present results indicate that the corresponding antigen, evidently acrosin, and PNA-positive material are liberated during the acrosome reaction which suggests that they are not bound to the inner acrosomal membrane but are components of the acrosomal matrix. PMID- 3100455 TI - Testicular volume, semen profile and serum hormone levels in fertile Thai males. AB - The fertility profile of 307 Thai male volunteers whose wives were currently in early pregnancy was established by genital examination, semen analysis and serum hormone analysis. Ninety percent of the subjects had testicular volumes of 12-25 ml (mean 17.2 ml) which was found to relate to body weight, height and the ponderal index as well as to the sperm count. However, values for semen analysis were significantly below the recognised standard for Caucasian males. There was an inverse relationship between testicular volume and the serum concentration of FSH, LH and prolactin. It is suggested that a common protocol for male fertility assessment should be used to establish standard parameters for racially different male populations. PMID- 3100457 TI - Epidermal growth factor stimulates lactate production and inhibits aromatization in cultured Sertoli cells from immature rats. AB - The addition of epidermal growth factor (EGF) at nanomolar concentrations to cultures of Sertoli cells from 16-day-old rats induced more than a 2-fold stimulation of lactate production after 12 h of incubation. The effects of EGF, insulin and FSH on lactate production were very similar and the concentrations that produced half maximal stimulation were 11, 22 and 25 ng/ml or, in molar terms, 1.8, 3.5 and 0.6 nM for EGF, insulin and FSH, respectively. No synergistic or additive effects of these hormones on lactate production could be demonstrated. In contrast, EGF inhibited FSH-stimulated oestradiol synthesis by more than 50%. Insulin had no effect on FSH-stimulated aromatization. PMID- 3100458 TI - Stimulation of ornithine decarboxylase in the rat prostate by seminal plasma inhibin. AB - The effect of seminal plasma inhibin on ornithine decarboxylase activity (ODC) in the rat prostate was studied. A single bolus injection of seminal plasma inhibin caused a 3- to 4-fold increase in ODC activity within 2 h whereas testicular ODC was unchanged. The ODC response to seminal plasma inhibin was neutralized by specific antibodies generated against the inhibin preparation. Another peptide, thyroid releasing hormone has no effect on prostatic ODC activity, but it blocked the increase in enzyme activity induced by treatment with seminal plasma inhibin. PMID- 3100459 TI - Generation of activated killer cells in tumor-bearing hosts. AB - Activated killer (AK) cells were generated in spleen-cell cultures derived from tumor-bearing hosts (TS) whereas, under the same conditions, cultured normal spleen cells (NS) gave little cytotoxicity. The AK effectors were primarily Thy1+, AGM1- and Lyt2- and thus were neither classic cytotoxic T lymphocytes (CTL) nor classic NK cells. These AK cells selectively killed tumor targets of different etiologic origins and did not kill concanavalin-A-induced lymphoblasts. The broad target-cell reactivity of these AK cells was also confirmed by cold target-inhibition experiments. Generation of AK cell correlated with interleukin 2 (IL-2) production, and the levels of AK cells generation paralleled those of IL 2 production. Furthermore, the generation of AK cells was blocked by the anti-IL 2 receptor monoclonal antibody (MAb) (alpha IL-2R), indicating that IL-2 was involved, and thus these AK cells were lymphokine-activated killer (LAK) cells. We previously showed that the expression of AGM1 on LAK precursors disappeared when they differentiated into LAK effectors, indicating that the activated LAK cells lacked AGM1. When examining the serologic phenotype of the LAK precursors in tumor-bearing hosts, we found that they lacked AGM1, which suggested that these LAK precursors were in an "activated" state. These cells were still Thy1-, and were thus different from fully activated LAK effectors which were Thy1+ cells, indicating that the full differentiation of LAK cells in vivo was arrested in the tumor-bearing hosts. We also found that the presence of small amounts of X irradiated tumor cells prevented the generation of AK cells. These findings suggest that, in the tumor-bearing hosts, the presence of tumor cells triggers the activation of AK precursors; however, the same tumor cells may also be immunosuppressive, which prevents the full differentiation of AK precursors into AK effectors. PMID- 3100460 TI - Effects of DL-alpha-difluoromethylornithine on the growth and metastasis of B16 melanoma in vivo. AB - The effects of DL-alpha-difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, on the growth of experimental mouse B16-F10 melanoma cells were investigated. DFMO (3%) in drinking water was administered to B16-F10 melanoma-bearing mice. At 24 days, B16-F10 melanomas in DFMO-fed mice weighed 75% less than those in control mice (p less than 0.001). DFMO reduced putrescine and spermidine levels in B16-F10 melanoma by 98% and 84%, respectively, and prolonged the mean survival time from 25.9 +/- 1.2 to 35.7 +/- 2.2 days (p less than 0.001). The effects of DFMO on experimental metastasis were also investigated. DFMO treatment resulted in a significant decrease in pulmonary metastasis induced by i.v. injection of B16-F10 melanoma cells. PMID- 3100461 TI - The effectiveness of transcutaneous nitrate preparations for angina pectoris. PMID- 3100462 TI - Low ceiling respiratory depression by ciramadol. AB - Ciramadol, an agonist-antagonist analgesic of lesser milligram potency than morphine, given intravenously at 30 mg/70 kg produced respiratory depression equivalent to that observed with morphine 10 mg/70 kg. Respiratory depression was measured in terms of drug induced displacement of the carbon dioxide response curve of healthy volunteers. In contrast to the progressive respiratory depression by each 10 mg/70 kg increment of morphine, further doses of ciramadol up to 90 mg/70 kg failed to increase respiratory depression. The ceiling of respiratory depression by ciramadol was half the ceiling previously demonstrated for nalbuphine and dezocine. Ceiling respiratory depression may be a general characteristic of agonist-antagonist type analgesics in contrast to pure agonist analgesics. PMID- 3100463 TI - A placebo-controlled assessment of mequitazine and astemizole in tests of psychomotor ability. AB - This study was a single and repeated dose comparison of mequitazine 5 mg, astemizole 10 mg and placebo and their effects on CNS activity, psychomotor performance and subjective appraisals of alertness. Nine Caucasian female volunteers aged between 29 and 40 years, declared healthy following a medical examination and who showed sensitivity to antihistamine sedation, were admitted to the study. Subjects were allocated to treatment in a randomized block design by which each subject received single and repeat doses of mequitazine 5 mg, astemizole 10 mg and placebo under double-blind conditions. Objective assessments (choice reaction time, critical flicker fusion threshold, simulated car tracking task, Stroop test) and subjective assessments (sedation and sleep rating scales, adverse effects and event recording) were made. Assessments were performed on day 1 and day 8 at pre-dosing (0 h) and at 1.5, 3.5 and 5.5 h following drug administration. Choice reaction times were dissimilar 5.5 h post-drug administration, the mequitazine group having a reaction time comparable to baseline and faster than the astemizole and placebo treatment groups. However, none of the treatments produced any significant or consistent effects when assessed on objective and subjective measures of performance, critical flicker fusion threshold, sedation and sleep and there were no treatment differences in the nature and number of adverse effects reported. PMID- 3100464 TI - Effect of chronic ingestion of a prostaglandin E analogue on immunologic function in healthy elderly subjects. AB - The immunologic effects of an oral prostaglandin E1 (PGE1) analogue were tested in 25 individuals over age 65, compared to 25 individuals given placebo. Elderly subjects were chosen because previous in vitro studies had found an increased sensitivity to PGE of lymphocytes in older subjects. After 2 weeks of ingestion of PGE analogue or placebo, there was a small but statistically significant decrease in IgM-rheumatoid factor in the PGE analogue group compared to control and a significant decrease in the in vitro sensitivity of lymphocytes from the PGE analogue group to inhibition by PGE. There were no differences in total lymphocyte count, T cell or T cell subset count, delayed hypersensitivity skin test reactivity, serum immunoglobulins, or response to mitogens between the two groups. Administration of an oral PGE analogue to normal elderly individuals is not associated with any detrimental effects on immunologic function after 2 weeks. PMID- 3100465 TI - In vitro effect of lymphoblastoid alpha-interferon on subpopulations of effector cells mediating cytotoxicity for autologous hepatocytes in hepatitis B and non-A, non-B. AB - Controlled clinical trials are currently under way to assess the efficacy of interferon (IFN) in hepatitis B virus (HBV) infection. In the present study, T enriched and non-T-enriched lymphocytes from six patients with acute and six patients with chronic HBV infection were cocultured with autologous liver cells with and without alpha-IFN (lymphoblastoid) at a concentration of 1000 U/ml of culture medium, in an 18 h cytotoxicity assay. IFN produced a significant enhancement of non-T-cell cytotoxicity in patients with acute and chronic HBV infection, from 34.3 +/- 19.6% to 60.0 +/- 11.2%, P less than 0.03, and from 41.2 +/- 17.2% to 65.5 +/- 9.8%, P less than 0.01, respectively. In contrast, no significant effect was observed on T cell-mediated cytotoxicity in either group of patients. The in vitro effect of alpha-IFN was also evaluated in four patients who developed chronic non-A, non-B hepatitis following blood transfusion, but no significant stimulatory effect was noted on either T- or non-T cell cytotoxicity. Similarly, no significant increase was observed in control subjects. The significant enhancement of non-T cell cytotoxicity, but not of T-cell cytotoxicity, for autologous hepatocytes in HBV infection suggests that alpha-IFN produces a selective stimulatory effect on non-T cells. The absence of a similar effect in patients with chronic non-A, non-B hepatitis and control subjects suggests that HBV infection alters the susceptibility of hepatocytes to IFN stimulated non-T cell damage. PMID- 3100467 TI - Human growth hormone, cortisol, and acid-base balance changes after hyperventilation and breath-holding. AB - The purpose of this study was to investigate the effects of hyperventilation and breath-holding on hormonal activity and the acid-base balance in men. Three different experimental procedures were carried out with 11 trained subjects aged 24.5 years. In experiment I, all subjects performed hyperventilation for 3 min maintaining a paced ventilation of 47 l X min-1. In experiment II, they performed a threefold maximal voluntary breath-holding, separated by 1-min periods of normal breathing. Experiment III consisted of a combination of hyperventilation immediately followed by maximal voluntary breath-holding. Capillary blood samples were taken for determination of pO2, pCO2, and pH. Venous blood samples were drawn before and at the 5th and 30th min after the cessation of the applied procedure for RIA determination of human growth hormone (HGH) and cortisol. During the last 15 s of hyperventilation, pO2 increased to 89.4 +/- 16.2 mm Hg, pCO2 decreased to 19.6 +/- 1.6 mm Hg, and pH increased to 7.652 +/- 0.041. During the last 15 s of the third breath-holding, the results were pO2 = 58.0 +/- 5.1, pCO2 = 45.7 +/- 3.7, and pH = 7.367 +/- 0.053. In experiment III, the mean values were pO2 = 42.6 +/- 7.9 mmHg, pCO2 = 39.2 +/- 4.6 mmHg, and pH = 7.320 +/- 0.024. A significant hormonal response after the applied experimental procedures was found for HGH (1.5- to 5.56-fold increase) and cortisol (1.5- to 2.2-fold increase).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100466 TI - Unmodified performance in runners following anabolic steroid administration. AB - The effect of a low-dose treatment (10 mg/day) of stanozolol on the anaerobic threshold (AT) and on maximal velocity (Vmax) was studied in ten well-trained runners in a 6-week trial experiment. The serum levels of testosterone (T), interstitial cell-stimulating hormone (ICSH), and of follicle-stimulating hormone (FSH) were determined before, during, and after the steroid administration. No improvements of AT and Vmax were found. No improvement of the competition running times was observed during the experimental period. The ICSH and FSH serum concentrations did not change significantly, while a marked decrease of the T serum concentration was observed. It is concluded that a low-dose treatment of stanozolol, sufficient to depress the testicular function, does not improve athletic performance. PMID- 3100469 TI - Involvement of calcium and dipicolinic acid in the resistance of Bacillus cereus BIS-59 spores to u.v. and gamma radiations. AB - The role of dipicolinic acid (DPA) in determining the resistance of Bacillus cereus spores to u.v. and gamma radiation was investigated. B. cereus BIS-59 spores containing varying amounts of DPA were prepared by appropriate compositional adjustments in the secondary media. Compared with spores containing 6 per cent DPA (dry weight) those containing 0.8 per cent DPA were far more sensitive to u.v. radiation. Similar u.v. radiation sensitivity was also found in respect of a DPA-less mutant of B. cereus T 6A 1. Pre-treatment of DPA deficient spores (of wild type or mutant B. cereus) with DPA or the presence of DPA during irradiation resulted in increased resistance of these spores to u.v. radiation. In the range 0.2 to 1 per cent DPA content of spores of B. cereus BIS-59, a striking inverse relationship could be discerned between the DPA content and the number of spore photo-products (5-thymidyl, 5,6-dihydrothymine) formed in DNA and spore viability. The resistance of B. cereus spores to gamma radiation did not seem to be influenced by their DPA content. PMID- 3100470 TI - The negotiating machinery of the Danish Nurses Organization. AB - The author presents the successful negotiating machinery and the possibilities of the Danish Nurses Organization in the actual economic and political situation in Denmark. This paper was presented at the ICN SEW Resource Group meeting in Geneva. PMID- 3100468 TI - Sex hormones, lipids, lipoprotein cholesterols, and apolipoproteins in normal and obese subjects: atherogenic relationships. AB - Our aim in the current study of 20 normal controls, 28 overweight, and 26 severely overweight (obese) subjects was to assess interrelationships of obesity, endogenous estradiol (E2) and testosterone (T), and the E2/T ratio with major independent explanatory variables for coronary heart disease (CHD), including lipids, lipoproteins, and apolipoproteins. Most of the lipid and lipoprotein variables (total, high-, low-, and very-low-density lipoprotein cholesterols) as well as apolipoproteins A1, A2, and B did not vary significantly with the presence of obesity. With increasing relative ponderosity, there were, however, increasing levels of total triglycerides and VLDL triglyceride. Levels of FSH, LH, prolactin, and testosterone did not differ significantly with obesity. The obese subjects had the highest E2 and E2/T levels; overweight subjects had intermediate levels which were also significantly higher than in the controls. Using multiple regression analyses, in obese subjects increasing T was associated with increasing apo B, and increasing E2 was correlated with decreasing apo A1. Opposite relationships were found in the normal controls where increasing T and increasing Quetelet indices were associated with diminished apo B and increasing E2 was associated with increasing A1. Obesity's association with increased CHD risk may be mediated through increasing E2 and apo B and reducing apo A1. Since obese subjects have higher E2 levels and often have lower T, they are likely to have a pattern of endogenous sex hormones (higher E2, lower T, higher E2/T ratios) similar to those observed in young men with premature myocardial infarction. PMID- 3100471 TI - Biology and structure of scrapie prions. PMID- 3100472 TI - Human platelet-tumor cell interactions vary with the tumor cell lines. AB - Platelets may promote the development of metastasis, and tumor cells that aggregate platelets are believed to be more malignant. We studied three different human mammary carcinoma cell lines, which had different interactions with human platelet-rich plasma (PRP). The MCF-7 and the T47-D cell lines induced an adenosine diphosphate (ADP)-mediated platelet aggregation. The third cell line, MDA-MB 231 did not induce any platelet aggregation. On the contrary, this cell line inhibited ADP- and arachidonic acid-induced platelet aggregation. This inhibiting activity is mainly adenosine-mediated. The mechanism by which platelets may contribute to the dissemination of cancer could be related to platelet growth factors. MCF-7 and T47-D cell lines induced a release of platelet derived growth factor (PDGF). On the contrary, the MDA-MB 231 cell line did not induce any platelet release. The role of these platelet growth factors in tumor cell growth is discussed. PMID- 3100473 TI - Immunohistochemical localization for aldose reductase in diabetic lenses. AB - Sugar cataract formation has been demonstrated to result from lenticular sorbitol accumulation. In the lens, the activity of aldose reductase has been observed to increase with the onset of diabetes, while the activity of sorbitol dehydrogenase decreases. This shift in activities of these two Sorbitol Pathway enzymes favors the increased accumulation of sorbitol. Immunohistochemical studies with antibodies prepared against purified rat lens aldose reductase reveal a striking increase in immunoreactive positive staining for aldose reductase in lenses from diabetic rats. Two weeks after the onset of diabetes, increased immunohistochemical staining for aldose reductase appears beneath the epithelial region where water cleft formation occurs, and the intensity of this staining increases with the formation of vacuoles. By 6-8 weeks, the presence of large vacuoles and areas of liquifaction containing dense immunoreactive stain can be observed. Examination of human cataractous lenses with antibodies prepared against purified human placenta aldose reductase suggest similar increases in immunoreactive staining in the human diabetic lens. Cataractous lenses from diabetic patients revealed increased immunoreactive staining for aldose reductase, which was associated with the presence of vacuoles in both the anterior or posterior superficial cortical layers. Examination of similar vacuole containing regions from non-diabetic cataractous lenses revealed no increase in immunoreactive staining for aldose reductase. These results suggest that the enhanced activity of aldose reductase observed in diabetes is due to an increased amount of enzyme, rather than enzyme activation. PMID- 3100474 TI - Extracellular release of acid hydrolases from cultured retinal pigmented epithelium. AB - The intracellular and extracellular distribution of acid hydrolases in cultured retinal pigmented epithelium (RPE) was studied. Incubation of cultured RPE in medium containing 20 mM mannose-6-phosphate resulted in the extracellular release of approximately 15% of the cell-associated activity of several acid hydrolases. This represents an approximate 120% increase over control levels after 24 hr of culture with 20 mM mannose-6-phosphate. The extracellular release is not due to cell lysis, since no release of the cytoplasmic marker lactate dehydrogenase was seen. n-Acetyl-beta-glucosaminidase, alpha-mannosidase, and beta-glucuronidase were released into the extracellular medium, while acid phosphatase and beta glucosidase were not. The release was specific for mannose-6-phosphate, and was dose-dependent. Inhibition of protein synthesis by treatment of RPE cells with cycloheximide (100 micrograms/ml) inhibited extracellular acid hydrolase release. RPE cells exhibited n-Acetyl-beta-glucosaminidase bound to the cell surface via a mannose-6-phosphate sensitive receptor. These results demonstrate a specific extracellular release of acid hydrolases by RPE and the presence of at least one acid hydrolase on the RPE cell surface. This may represent a mechanism for control of cell surface and extracellular levels of these enzymes in RPE via the mannose-6-phosphate receptor. PMID- 3100475 TI - Plasmid-mediated tetracycline-resistant Neisseria gonorrhoeae. PMID- 3100476 TI - Calcium entry blocker: treatment in acute pain in cluster headache patients. AB - 15 chronic cluster headache patients in whom pain was induced by nitroglycerin received acute intravenous treatment with a calcium entry blocker. At the time of peak pain we noted a sudden decrease after the Verapamil injection. The mechanism by which the calcium entry blocker afforded relief is unlikely to have been vasodilatation in patients whose blood vessels had just been dilated by nitroglycerin. A more probable mechanism is blockade of the release of the pain inducing neurotransmitters. The vasodilatation phase is not a primary factor in the onset of pain. PMID- 3100477 TI - T-lymphocyte subsets modifications in multiple sclerosis: correlation with clinical disease activity. AB - Serial analyses of peripheral blood T-lymphocyte subsets were performed in 280 samples collected over a 27 months period from 14 multiple sclerosis patients. A significant decrease of T8+ cells was found in 47.1% (47/87) of blood samples collected within four weeks of onset of a relapse opposed to 2.1% (1/47) of samples collected during the four weeks before a relapse and to 3.4% (5/146) of those collected over four weeks after a relapse. Changes of T-cells subsets appear to correlate with disease activity, but normal findings observed before relapses suggest that the decrease of T8+ cells cannot be used as valid predictor of relapse. PMID- 3100478 TI - Towards a general model of health detriment cost evaluation. PMID- 3100479 TI - Home parenteral antibiotic therapy, Part I: An overview of program design. PMID- 3100480 TI - Home tube feedings: gastrointestinal complications. PMID- 3100481 TI - LFA-1 and other accessory molecules functioning in adhesions of T and B lymphocytes. AB - Adhesions of lymphocytes, among themselves or with other cell types, are necessary for most steps in immune responses including both induction and effector phases. Among adhesions of T cells involving specific immunological recognition, CTL-target adhesions have been the most studied. Although CTL mediated killing is highly specific (specific/nonspecific lytic activity 50 fold), CTL-target adhesion (conjugation) is less so. In the mouse, specificity of conjugation has typically been four to eightfold. Two recent studies with cloned human CTL found much less specificity of conjugation, from one-fold (no specificity) to 1.5-fold. Thus, with cloned human CTL, adhesion may occur promiscuously with any potential target; recognition following adhesion is necessary for lethal hit delivery. The fact that antibodies to the antigen receptor (Ti or CD3) inhibit killing without inhibiting CTL-target conjugation supports this view. The ability of lymphocytes to form nonspecific adhesions, plus the dependence of even the specific mouse adhesions on temperature, metabolic energy, magnesium, and an intact cytoskeleton suggest that the bulk of the strength of T lymphocyte adhesions are not simply the sum of the bonds between antigen receptors (Ti) and antigen. Lymphocytes evidently possess separate "adhesion strengthening" mechanisms. The similarities in the properties of CTL-target adhesions and antigen-independent homotypic B lymphocyte adhesions (Table 2) suggest that at least some of these mechanisms are widely used among cells of hematopoietic origin. MoAbs to most lymphocyte surface molecules, when bound to the living lymphocyte membrane, have no evident functional effects on lymphocyte function. However, a minority can either activate or inhibit lymphocyte functions. Such antibodies identify "leukocyte (or lymphocyte) function-associated antigens," or LFAs (not all of which happen to have "LFA" in their names, Table 1). Most of the inhibitory antibodies inhibit lymphocyte adhesions, and this appears to account for their inhibitory effects on functions such as killing or proliferation. The fact that the binding of antibodies to a particular membrane glycoprotein inhibits adhesion does not guarantee that the glycoprotein in question is a direct participant in adhesion (one of the "glue" molecules). However, there is scanty evidence in support of indirect "negative signals" that may be induced by such antibodies, and direct participation of most LFAs in adhesion seems likely.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3100482 TI - Radiotherapeutic computed tomography with scanned photon beams. AB - Radiotherapeutic computed tomography is a powerful technique to generate anatomical transversal tomograms of the patient in treatment position by using the therapy beam from the treatment unit. For this purpose the treatment unit has to be equipped with a detector array that can detect the beam transmitted through the patient and a computer that analyzes the data and performs the back projection. When the treatment unit uses scanned elementary photon beams, the only practical technique available for generating high quality high energy photon beams, the operation principle and, to some extent, the image quality is similar to that of a 3rd generation CT-scanner. The optimum choice of detection geometry and type of radiation detectors for radiotherapeutic computed tomography particularly at high photon energies are discussed indicating the merits of BGO (bismuthgermanate) or CWO (cadmiumtungstate) photodiod arrays. The first tomographic images of a thorax phantom at an acceleration potential of 50 MV using such detectors are presented. The image contrast is similar to that for 300 kV X rays mainly because the considerable influence of pair production at 50 MV. Line spread and modulation transfer functions are presented indicating a resolution of the order of two millimeters using a crystal thickness of 5 mm. The advantages with radiotherapeutic computed tomography, beside forming a new general communication channel between different diagnostic techniques, dose planning, and radiation delivery, are the elimination of position errors and the provision of exact attenuation data for dose planning. PMID- 3100484 TI - Sexually transmitted diseases in children. PMID- 3100483 TI - Chlamydia trachomatis detection in adolescents. A comparison of direct specimen and tissue culture methods. AB - We compared tissue cell culture isolation with the Microtrak fluorescent monoclonal antibody direct specimen test for detection of endocervical Chlamydia trachomatis in an inner-city population of sexually active Black and Hispanic adolescent girls. Of the 95 patients screened, C. trachomatis was identified in 26.3%. The sensitivity of the direct specimen test was 91.7%, and its specificity was 98.6%. The positive predictive value was 95.6%, and the negative predictive value was 97.2%. No significant difference was found between Blacks (28.6%) and Hispanics (24.1%) in the incidence of endocervical C. trachomatis, nor was the use of an oral contraceptive significantly associated with the diagnosis of C. trachomatis (p greater than 0.10). Neisseria gonorrhoeae was isolated in 8.4% of the patients. The direct specimen test appears to be an accurate and convenient method of screening sexually active adolescent girls for genital C. trachomatis. Further study is needed to determine if an oral contraceptive increases the risk of Chlamydia infection in adolescents. PMID- 3100485 TI - Reversal of the surface effects of chlorhexidine diacetate on cells of Providencia stuartii. AB - Chlorhexidine diacetate (CHA) increased the hydrophobicity of the cell surface of cells of three strains of Providencia stuartii. Removal of at least some of the CHA from the cells by washing them with an appropriate antidote partially reversed the hydrophobicity-increasing action of the biguanide. The effects of other treatments on cell surface hydrophobicity were examined with these strains and, for comparison, with two strains each of Escherichia coli and Pseudomonas aeruginosa: ethylenediamine tetraacetic acid affected all strains, although not to the same extent, whereas thermal injury (55 degrees C) produced marked changes only with the two E. coli strains. PMID- 3100486 TI - Growth of lipolytic psychrotrophic pseudomonads in raw and ultra-heat-treated milk. AB - The lipolytic floras of 36 raw milk samples showing lipolytic defects were dominated by pseudomonads. Representative lipolytic isolates were selected and tested for growth, lipase activity and lipolysis in ultra-heat-treated milk at temperatures ranging from 5 degrees to 30 degrees C. Pseudomonas fluorescens was the most frequently encountered species but Ps. fragi was found to cause more severe lipolytic defects in both single and mixed strain milk cultures. A representative strain of Ps. fragi multiplied faster in cold-stored milk than did three representative strains of Ps. fluorescens. The lipases produced by Ps. fragi strains were more heat-stable than those produced by Ps. fluorescens strains. PMID- 3100487 TI - Emergence of ceftriaxone-resistant strains of Pseudomonas aeruginosa in cystic fibrosis patients. AB - Cystic fibrosis patients with Pseudomonas aeruginosa chest infections were treated with ceftriaxone alone or ceftriaxone plus tobramycin. P. aeruginosa strains isolated before and after treatment were studied for changes in sensitivity to ceftriaxone. After therapy with either the single agent or the combination six strains from five patients were found to be resistant to ceftriaxone. No resistant strains were isolated before therapy. Resistance was mediated by excess production of Id beta-lactamase which in five of six strains was permanently derepressed. Bacterial resistance appearing during therapy reduces the value of this antibiotic in cystic fibrosis chest infections. PMID- 3100488 TI - The postantibiotic effect of imipenem. PMID- 3100489 TI - Epidemiology of resistance in Neisseria gonorrhoeae. AB - In the face of almost unique selective pressures many strains of gonococci have become increasingly resistant to antibiotics. Both chromosomal mutation and acquisition of plasmids are involved. However, whereas there have probably been multiple selections of many mutation events determining chromosomal resistance, evidence suggests that a very limited number of plasmid acquisitions has occurred, with subsequent spread within members of the species. PMID- 3100490 TI - Ciprofloxacin in the treatment of Pseudomonas infection in cystic fibrosis patients. AB - Ten patients with cystic fibrosis received 19 therapeutic courses of ciprofloxacin at a dose of 750 mg orally twice daily. The length of therapy ranged from two to five weeks except for one patient who was treated for six weeks. The mean peak serum concentration of ciprofloxacin was 3.41 mg/l and the mean trough level was 1.11 mg/l. For comparison nine patients were treated with the combination of azlocillin at a dose of 350 mg/kg/day in four divided doses and tobramycin at an initial dose of 9 mg/kg/day in three divided doses. All patients were infected with Pseudomonas aeruginosa except for one patient in whom P. cepacia grew in the sputum cultures; the MICs of ciprofloxacin ranged from 0.05 to 1.56 mg/l. The results obtained with these two therapeutic regimens were comparable. The patient treated for P. cepacia infection developed resistance to ciprofloxacin (MIC greater than 6.24 mg/l) during the course of treatment. Ciprofloxacin appears to be an alternative treatment to the use of an aminoglycoside and a penicillin in cystic fibrosis patients. PMID- 3100491 TI - Bactericidal activity of ciprofloxacin alone and in combination with azlocillin in an in-vitro capillary model. AB - An in-vitro pharmacokinetic model was used to study the bactericidal activity of ciprofloxacin, alone and in combination with azlocillin. Ciprofloxacin alone produced excellent bactericidal activity against highly susceptible strains of Escherichia coli and Klebsiella pneumoniae. Against a strain of Pseudomonas aeruginosa, ciprofloxacin in clinically achievable dosing schedules produced a rapid bactericidal effect, but bacterial regrowth occurred. Azlocillin in combination with ciprofloxacin produced a rapid bacterial kill and regrowth was prevented. Further consideration of the clinical role of this combination is warranted. PMID- 3100492 TI - Ciprofloxacin in experimental Pseudomonas aeruginosa meningitis in rabbits. AB - The potential of ciprofloxacin for the therapy of Pseudomonas aeruginosa meningitis was evaluated in an animal model by determining the penetration of the drug into CSF, its concentration-dependent killing characteristics in vivo, and its relative efficacy compared with ceftazidime and tobramycin. Meningitis was produced in 40 rabbits by intracisternal injection of 3 X 10(7) organisms. The drugs were administered intravenously over seven hours, and simultaneously serum and CSF samples were taken at 0, 1, 3, 5, and 7 h for determination of drug concentration and CSF bacterial counts. The percentage penetration of ciprofloxacin (18.4 +/- 12.3; mean +/- standard deviation) in infected rabbits was substantially increased over that found in uninfected rabbits (4.1 +/- 1.3). The rate of bacterial killing for animals treated with ceftazidime (100 mg/kg/h) and high doses of tobramycin (2.5 mg/kg/h) was -0.51 +/- 0.13 (log10 cfu/ml/h). This was similar to the rate of killing (-0.48 +/- 0.2) found when ciprofloxacin was infused at 5 mg/kg/h, a dose that produced a mean serum level of 6.7 +/- 4.6 mg/l, which corresponds to concentrations achievable in humans. As dosages were increased (15 and 30 mg/kg/h), the rate of bacterial killing also increased ( 0.70 +/- 0.1 and -0.89 +/- 0.4 respectively; r = 0.7407; P less than 0.01). The drugs shows promise in the treatment of pseudomonas meningitis. PMID- 3100494 TI - Hyperventilation, alkalosis, prostaglandins, and pulmonary circulation of the newborn. AB - This study was designed to determine whether the effects of hyperventilation on the pulmonary circulation of the newborn lamb were 1) due to mechanical factors or to respiratory alkalosis; and 2) mediated by prostaglandins. Six control lambs were studied during normal ventilation and during hyperventilation with, and without, decreased carbon dioxide (CO2). Five lambs were given indomethacin and studied similarly. In control lambs, hyperventilation with decreased CO2 decreased pulmonary arterial pressure from 26 +/- 2.2 to 18 +/- 1.0 (SE) Torr (P less than or equal to 0.005) and pulmonary vascular resistance from 0.099 +/- 0.035 to 0.070 +/- 0.011 Torr X kg-1 X min-1 (P less than or equal to 0.015). Hyperventilation with normal CO2 did not affect the pulmonary circulation. Hyperventilation with decreased CO2 increased pulmonary arterial concentrations of 6-ketoprostaglandin F1 alpha, a major metabolite of prostacyclin, in control lambs but not in the indomethacin-treated lambs. However, it affected the pulmonary circulation of the control- and indomethacin-treated lambs similarly. In conclusion, hyperventilation affected the pulmonary circulation by respiratory alkalosis not by mechanical factors and prostaglandins did not mediate its effects. PMID- 3100493 TI - The rib cage in normal and emphysematous subjects: a roentgenographic approach. AB - The configuration and motion of the bony rib cage were studied from lateral chest roentgenograms in 10 young normal subjects (YN), 12 elderly normal subjects, and 12 hyperinflated emphysematous patients [chronic obstructive pulmonary disease subjects (COPD), mean total lung capacity (TLC) 133% of predicted]. The acute angles formed by the fourth through seventh ribs with an axial reference plane were measured at residual volume, functional residual capacity, and TLC in both supine and standing positions and correlated with corresponding lung volumes. both rib angles (RA) and changes in RA with lung volume were greatest with the fourth rib and decreased progressively going down (caudad) the chest. At TLC the RA of upper ribs was significantly less in EN and significantly greater in COPD than in YN. RA's were greater supine than standing. When RA information was used together with autopsy data on the angles formed by intercostal muscles with adjacent ribs, intercostal muscle lengths in hyperinflation could be calculated. Computed intercostal muscle length data suggested that hyperinflation should not be associated with degrees of intercostal muscle shortening or overstretching, that would interfere seriously with tension generation. PMID- 3100495 TI - Effect of dopamine on transient ventilatory response to exercise. AB - The effect of exogenous dopamine on the development of exercise hyperpnea was studied. Using a bicycle ergometer, five subjects performed repetitive square wave work-load testing from unloaded pedaling to 80% of each subject's estimated anaerobic threshold. The breath-by-breath ventilation (VE), CO2 production (VCO2), and O2 consumption (VO2) responses were analyzed by curve fitting a first order exponential model. Comparisons were made between control experiments and experiments with a 3-micrograms X kg-1 X min-1 intravenous infusion of dopamine. Steady-state VE, VCO2 and VO2 were unchanged by the dopamine infusion, both during unloaded pedaling and at the heavier work load. The time constants for the increase in VE (tau VE) and VCO2 (tau CO2) were significantly (P less than 0.05) slowed (tau VE = 56.5 +/- 16.4 s for control, and tau VE = 76.4 +/- 26.6 s for dopamine; tau CO2 = 51.5 +/- 10.6 s for control, and tau CO2 = 64.8 +/- 17.4 s for dopamine) (mean +/- SD), but the time constant for VO2 (tau O2) was not significantly affected (tau O2 = 27.5 +/- 11.7 s for control, and tau O2 = 31.0 +/- 10.1 s for dopamine). We conclude that ablation of carotid body chemosensitivity with dopamine slows the transient ventilatory response to exercise while leaving the steady-state response unaffected. PMID- 3100496 TI - Regional pulmonary blood flow during 96 hours of hypoxia in conscious sheep. AB - The effects of acute hypoxia on regional pulmonary perfusion have been studied previously in anesthetized, artificially ventilated sheep (J. Appl. Physiol. 56: 338-342, 1984). That study indicated that a rise in pulmonary arterial pressure was associated with a shift of pulmonary blood flow toward dorsal (nondependent) areas of the lung. This study examined the relationship between the pulmonary arterial pressor response and regional pulmonary blood flow in five conscious, standing ewes during 96 h of normobaric hypoxia. The sheep were made hypoxic by N2 dilution in an environmental chamber [arterial O2 tension (PaO2) = 37-42 Torr, arterial CO2 tension (PaCO2) = 25-30 Torr]. Regional pulmonary blood flow was calculated by injecting 15-micron radiolabeled microspheres into the superior vena cava during normoxia and at 24-h intervals of hypoxia. Pulmonary arterial pressure increased from 12 Torr during normoxia to 19-22 Torr throughout hypoxia (alpha less than 0.049). Pulmonary blood flow, expressed as %QCO or ml X min-1 X g-1, did not shift among dorsal and ventral regions during hypoxia (alpha greater than 0.25); nor were there interlobar shifts of blood flow (alpha greater than 0.10). These data suggest that conscious, standing sheep do not demonstrate a shift in pulmonary blood flow during 96 h of normobaric hypoxia even though pulmonary arterial pressure rises 7-10 Torr. We question whether global hypoxic pulmonary vasoconstriction is, by itself, beneficial to the sheep. PMID- 3100498 TI - Constant-flow ventilation in pigs. AB - Constant-flow ventilation (CFV) is a ventilatory technique in which physiological blood gases can be maintained in dogs by a constant flow of fresh gas introduced via two catheters placed in the main-stem bronchi (J. Appl. Physiol. 53: 483-489, 1982). High-velocity gas exiting from the catheters can create uneven pressure differences in adjacent lung segments, and these pressure differences could lead to gas flow through collateral channels. To examine this hypothesis, we studied CFV in pigs, animals known to have a high resistance to collateral ventilation. In three pigs we examined steady-state gas exchange, and in six others we studied unsteady gas exchange at three flow rates (20, 35, and 50 l/min) and three catheter positions (0.5, 1.5, and 2.5 cm distal to the tracheal carina). During steady-state runs we were unable to attain normocapnia; the arterial CO2 partial pressure (PaCO2) was approximately 300 Torr at all flow rates and all catheter positions, compared with 20-50 Torr at similar flows and positions in dogs studied previously. The initial unsteady gas-exchange experiments indicated no consistent effect of catheter position or flow rate on the rate of rise of PaCO2. In three other pigs, the rates of rise of PaCO2 were compared with the rates observed with apneic oxygenation (AO). At the maximum flow and deepest position, the rate of rise of PaCO2 was lower during CFV than during AO. These data suggest that flow through collateral channels might be important in producing adequate gas transport during CFV; however, other factors such as airway morphometry and the effects of cardiogenic oscillations may explain the differences between the results in pigs and dogs. PMID- 3100497 TI - Ventilatory response during CO2 inhalation after airway anesthesia with lidocaine. AB - Airway anesthesia with inhaled aerosolized lidocaine has been associated with increases in minute ventilation (VE) and mean inspiratory flow rate (VT/TI) during CO2 inhalation. However, it is unclear whether these increases are local effects of the anesthesia or systemic effects of absorbed and circulating lidocaine. To evaluate this 20 normal subjects were treated on separate days with aerosolized lidocaine, intravenous lidocaine, aerosolized control solution, or intravenous control solution, and the effects of each treatment on VE and VT/TI were determined and compared during room-air breathing and inhalation of 5% CO2 95% O2. None of the treatments altered VE or VT/TI during room-air breathing. Aerosolized lidocaine produced small (5.9-6.0%) increases in VE and VT/TI during CO2 inhalation, but these effects were not present after intravenous lidocaine despite equivalent lidocaine blood levels. We concluded that the increases in VE and VT/TI after aerosolized lidocaine were local effects of airway anesthesia rather than systemic effects of absorbed and circulating lidocaine. PMID- 3100499 TI - Acid-base effects of altering plasma protein concentration in human blood in vitro. AB - We altered the concentration of plasma proteins in human blood in vitro by adding solutions with [Na+], [K+], and [Cl-] resembling those in normal blood plasma, either protein-free or with a high concentration of human albumin. After equilibrating the samples with a gas containing 5% CO2-12% O2-83% N2 at 37 degrees C, we measured pH, PCO2, and PO2; in separated plasma, we determined the concentrations of total plasma proteins and albumin and of the completely dissociated electrolytes (strong cations Na+, K+, Mg2+ and anions Cl-, citrate3 ). With PCO2 nearly constant (mean = 35.5 Torr; coefficient of variation = 0.02), lowering plasma protein concentration produced a metabolic alkalosis, whereas increasing plasma albumin concentration gave rise to a metabolic acidosis. These acid-base disturbances occurred independently of a minor variation in the balance between the sums of strong cations and anions. We quantified the dependence of several acid-base variables in plasma on albumin (or total protein) concentration. Normal plasma proteins are weak nonvolatile acids. Although their concentration is not regulated as part of acid-base homeostasis, hypoproteinemia and hyperalbuminemia per se produce alkalosis and acidosis, respectively. PMID- 3100500 TI - In vitro formation of fibrous septa by liver connective tissue cells. AB - Active fibrous septa are a common feature in liver fibrosis and cirrhosis. Their etiology and formation were studied using cultures of tissue fragments or cells included in collagen gels. Liver fragments obtained from patients with cirrhosis or severe schistosomal fibrosis were able to reorganize the gel and to form discrete, interconnecting fibrous septa composed of parallel arrays of collagen, subsequently colonized by migrating connective tissue cells. The same was obtained in cultures of fibrogranulomatous lesions isolated from schistosome infected mice livers. However, fragments of normal human and murine liver tissue did not show the capacity to form fibrous septa. Septa formation was also obtained in cultures of cell spheroids formed by liver connective tissue cells isolated from human fibrotic or cirrhotic liver tissues, but not with spheroids of normal skin fibroblasts or smooth muscle cells. This experimental model may represent the fibrous septa formation in vivo, depending on the activity of liver connective tissue cells. The ability of tissue fragments or cell spheroids to form septa in collagen gels might reflect the degree of fibrosis present in the liver tissue in vivo. PMID- 3100501 TI - Bioautographic method for evaluation of glycopeptide actaplanin in milk. AB - A bioautographic method is described that allows the identification and semiquantitation of residues of the glycopeptide antibiotic actaplanin in cow's milk at 0.01 ppm. The milk sample is precipitated with acetonitrile and the resultant pellet is extracted by a buffer. This extract is defatted, then chromatographed on an Amberlite resin column. Actaplanin is eluted with methanol HCl. Purified extract is then chromatographed on a cellulose thin layer, developed in a methanol-chloroform-ammonium hydroxide mixture. This thin layer chromatography increased the sensitivity of the determination by concentrating the actaplanin components in a single spot. The antibiotic was then detected by bioautography, using Bacillus subtilis as a test organism. Parameters influencing the diffusion of the antibiotic (namely, the nature and concentration of the agar agar), and the sensitivity of the test strain (namely, the nutritional value of the medium, and the addition of a synergistic inhibitor) have been optimized. PMID- 3100502 TI - Regulation of Bacillus subtilis macrofiber twist development by ions: effects of magnesium and ammonium. AB - The steady-state twist of Bacillus subtilis macrofibers produced by growth in complex medium was found to vary as a function of the magnesium and ammonium concentrations. Four categories of macrofiber-producing strains that differed in their response to temperature regulation of twist were studied. Macrofibers were cultured in the complex medium TB used in previous experiments and in two derivative media, T (consisting of Bacto Tryptose), in which most strains produced left-handed structures, and Be (consisting of Bacto Beef Extract), in which right-handed macrofibers arose. In nearly all cases, increasing concentrations of magnesium led to the production of macrofibers with greater right-handed twist. Some strains unable to form right-handed structures as a function of temperature could be made to do so by the addition of magnesium. Inversion from right- to left-handedness in strain FJ7 induced by temperature shift-up was blocked by the addition of magnesium. The presence of magnesium during a high-temperature pulse did not block the establishment of "memory," although it delayed the initiation of the transient inversion following return to low temperature. The twist state of macrofibers grown without a magnesium supplement was not instantaneously affected by the addition of magnesium. Such fibers were, however, protected from lysozyme attack and associated relaxation motions. Lysozyme degradation of purified cell walls (both intact and lacking teichoic acid) was also blocked by the addition of magnesium. Ammonium ions influenced macrofiber twist development towards the left-hand end of the twist spectrum. Macrofiber twist produced in mixtures of magnesium and ammonium was strain and medium dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100503 TI - Multiple species of Bacillus subtilis DNA alkyltransferase involved in the adaptive response to simple alkylating agents. AB - Three molecular species of methyl-accepting proteins exist in Bacillus subtilis cells, which collect methyl groups from methylated DNA. A 20-kilodalton (kDa) protein was constitutively present in the cells of the ada+ (proficient in adaptive response) strain as well as in those of six ada (deficient in adaptive response) mutant strains and was assigned to the O6-methylguanine:DNA methyltransferase. Another species of O6-methylguanine:DNA methyltransferase, which had a molecular size of 22 kDa, emerged after adaptive treatment of the ada+ but not any of the ada mutant cells. A 27-kDa methyl-accepting protein, which preferred methylated poly(dT) to methylated calf thymus DNA as a substrate, was assigned to the methylphosphotriester:DNA methyltransferase. It was produced, after adaptive treatment, in the cells of ada+, ada-3, ada-4, and ada-6 strains but not in the cells of ada-1, ada-2, or ada-5 strains. These results support and extend our proposition that ada mutants can be classified into two groups; one (the ada-4 group) is defective only in the inducible synthesis of O6 methylguanine:DNA methyltransferase (22-kDa protein), and the other (the ada-1 group) is deficient in the adaptive response in toto. The finding that inducible and constitutive methyltransferases reside in different molecular species of methyl-accepting proteins is intriguing compared with the regulatory mechanisms of the adaptive response to simple alkylating agents in other organisms. PMID- 3100504 TI - Cloning of the recA gene of Neisseria gonorrhoeae and construction of gonococcal recA mutants. AB - Interspecific complementation of an Escherichia coli recA mutant was used to identify recombinant plasmids within a genomic cosmid library derived from Neisseria gonorrhoeae that carry the gonococcal recA gene. These plasmids complement the E. coli recA mutation in both homologous recombination functions and resistance to DNA damaging agents. Subcloning, deletion mapping, and transposon Tn5 mutagenesis were used to localize the gonococcal gene responsible for suppression of the E. coli RecA- phenotype. Defined mutations in and near the cloned gonococcal recA gene were constructed in vitro and concurrently associated with a selectable genetic marker for N. gonorrhoeae and the mutated alleles were then reintroduced into the gonococcal chromosome by transformation-mediated marker rescue. This work resulted in the construction of two isogenic strains of N. gonorrhoeae, one of which expresses a reduced proficiency in homologous recombination activity and DNA repair function while the other displays an absolute deficiency in these capacities. These gonococcal mutants behaved similarly to recA mutants of other procaryotic species and displayed phenotypes consistent with the data obtained by heterospecific complementation in an E. coli recA host. The functional activities of the recA gene products of N. gonorrhoeae and E. coli appear to be highly conserved. PMID- 3100505 TI - In vivo regulation of histidine ammonia-lyase activity from Streptomyces griseus. AB - The enzyme histidine ammonia-lyase (histidase) is required for growth of Streptomyces griseus on L-histidine as the sole source of nitrogen. Histidase was induced by the inclusion of histidine in the medium, regardless of the presence of other carbon and nitrogen sources. Histidase activity was increased by a shift of culture incubation temperature from 30 to 37 degrees C. Conversely, upon induction of sporulation by either phosphate starvation or nutritional downshift, histidase underwent rapid inactivation. Nutrient replenishment fully reversed histidase inactivation while simultaneously permitting reinitiation of vegetative growth. In contrast to histidase inactivation during sporulation, histidase was activated after transition of a vegetatively growing culture to stationary phase. Although neither activation nor inactivation required de novo protein synthesis, inactivation appeared to involve a heat-labile protein. The results indicate that histidase activity is regulated in vivo by a process that responds to changes in the growth phase of the organism. PMID- 3100506 TI - Cell-density-dependent killing of Myxococcus xanthus by autocide AMV. AB - Autocide AMV of Myxococcus xanthus was purified and identified as phosphatidylethanolamine. Alkaline hydrolysis of AMV yielded a high proportion of mono- and diunsaturated fatty acids. The bactericidal activity of AMV on M. xanthus depended upon the density of target cells: the greater the cell density, the greater the killing by AMV. For example, at 2 U of AMV per ml, 0, 50, and 99% killing was measured with 2 X 10(4), 2 X 10(5), and 2 X 10(7) target cells per ml, respectively. The cell-density-dependent activity of AMV was also observed on solid medium. Studies with model lipid compounds suggest that the inhibitory activity of AMV is due to the fatty acid moiety, released from phosphatidylethanolamine by the concerted (enzymatic) activity of many cells. Mutants of M. xanthus selected for resistance to AMI (a mixture of fatty acids) were also resistant to AMV. The possible role of AMV in developmental lysis is discussed. PMID- 3100507 TI - Morphological and ultrastructural changes in vegetative cells and heterocysts of Anabaena variabilis grown with fructose. AB - The morphology and ultrastructure of Anabaena variabilis grown in medium with and without 40 mM fructose were compared. Vegetative cells and young heterocysts in fructose-supplemented medium were significantly larger, were filled with glycogen granules, and had fewer thylakoids. Developing heterocysts contained large numbers of glycogen granules well into mature stages, and envelope formation was precocious. As heterocysts enlarged in fructose medium, their shape became more broadly oblong compared with the more rectangular heterocysts in fructose-free medium. PMID- 3100508 TI - Purification and properties of 2,3-dihydroxybiphenyl dioxygenase from polychlorinated biphenyl-degrading Pseudomonas pseudoalcaligenes and Pseudomonas aeruginosa carrying the cloned bphC gene. AB - 2,3-Dihydroxybiphenyl dioxygenase, involved in biphenyl and polychlorinated biphenyl degradation, was purified from cell extracts of polychlorinated biphenyl degrading Pseudomonas pseudoalcaligenes KF707 and Pseudomonas aeruginosa PAO1161 carrying the cloned bphC gene (encoding 2,3-dihydroxybiphenyl dioxygenase). The purified enzyme contained ferrous iron as a prosthetic group. The specific activities decreased with the loss of ferrous iron from the enzyme, and the activity was restored by incubation with ferrous iron in the presence of cysteine. Addition of ferric iron caused the complete inactivation of the enzyme. The molecular weight was estimated to be 250,000. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed a single band with a molecular weight of 31,000, indicating that the enzyme consists of eight identical subunits. The enzyme was specific only for 2,3-dihydroxybiphenyl with a Km value of 87 microM. No significant activity was observed for 3,4-dihydroxybiphenyl, catechol, or 3 methyl- and 4-methylcatechol. The molecular weight, subunit structure, ferrous iron requirement, and NH2-terminal sequence (starting with serine up to 12 residues) were the same between the two enzymes obtained from KF707 and PAO1161 (bphC). PMID- 3100509 TI - Blunting of TSH response to TRH in chronic cocaine and phencyclidine abusers. AB - The TRH stimulation test was administered to 10 cocaine and 10 phencyclidine abusers as well as to 10 controls. No subjects had clinical evidence of depression. Significantly more blunting of the response of TSH to TRH was shown in cocaine and phencyclidine abusers compared with that seen in controls. No significant differences in blunting of response were seen between the cocaine and phencyclidine groups. PMID- 3100510 TI - Treatment of major affective disorder with fluvoxamine. AB - A placebo-controlled, double-blind study of 63 inpatients with major affective disorder was performed to compare the safety and efficacy of fluvoxamine and imipramine. Results indicate that fluvoxamine and imipramine are superior to placebo and demonstrate a trend toward superiority of fluvoxamine over imipramine. Fluvoxamine was generally well tolerated in most patients. PMID- 3100511 TI - Lithium-induced akathisia. PMID- 3100512 TI - Hardness changes and mineral loss in enamel during the intra oral cariogenicity test in the presence of 0.125% EHDP with or without 0.1% F-. AB - The effects of a high EHDP concentration (0.125%) were measured under Intra Oral Cariogenicity Test (ICT) conditions in the presence or absence of F- (0.1%). EHDP as well as EHDP supplemented with F- inhibited the softening of enamel slabs to a similar extent as measured by microhardness. Measurements of the calcium and phosphate levels as a function of depth showed that the addition of F- to the EHDP solution further decreased mineral loss in the deeper layers. The results suggest that the inhibition of demineralization of the enamel by EHDP and F- is due to inhibition of acid production by microorganisms. PMID- 3100513 TI - Synthesis of 7-mercaptoheptanoylthreonine phosphate and its activity in the methylcoenzyme M methylreductase system. AB - The structure of component B of the methylcoenzyme M methylreductase of Methanobacterium thermoautotrophicum was recently assigned as 7 mercaptoheptanoylthreonine phosphate (HS-HTP) (Noll, K. M., Rinehart, K. L., Jr., Tanner, R.S., and Wolfe, R.S. (1986) (Proc. Natl. Acad. Sci. U.S.A. 83, 4238 4242). We report here the chemical synthesis and biochemical activity of this compound. Thiourea and 7-bromoheptanoic acid were used to to synthesize 7,7' dithiodiheptanoic acid. This disulfide was then condensed with DL-threonine phosphate using N-hydroxysuccinimide and dicyclohexylcarbodiimide. The product was reduced with dithiothreitol to give HS-HTP. It could be oxidized in air in the presence of 2-mercaptoethanol to give the compound as it was isolated from cell extracts. The resulting product was identical to the authentic compound by 1H NMR spectroscopy, mass spectrometry, and coelution using high performance liquid chromatography. The synthetic compound is active in the in vitro methanogenic assay at concentrations comparable to the authentic compound. This confirms the structure of component B as HS-HTP and provides a means to synthesize quantities sufficient for studies of the methylreductase system. PMID- 3100514 TI - Structural characterization of the Mr = 55,000 antigen (ZP3) of porcine oocyte zona pellucida. Purification and characterization of alpha- and beta glycoproteins following digestion of lactosaminoglycan with endo-beta galactosidase. AB - The major macromolecular component of the porcine oocyte zona pellucida is a Mr = 55,000 antigen, termed ZP3, comprised of greater than 25 charge isomers. ZP3 was purified to apparent electrophoretic homogeneity from nonreduced, sodium dodecyl sulfate-treated porcine zonae pellucidae by chromatography on Sephacryl S-400 and hydroxylapatite resins. The carbohydrate moiety of purified ZP3 was comprised of a heterogeneous population of acidic lactosaminoglycans as evidenced by the saccharide composition and size distribution of glycopeptides produced by Pronase digestion of ZP3, as well as by the sensitivity of ZP3 to digestion with Escherichia freundii endo-beta-galactosidase. Endo-beta-galactosidase-digested ZP3 was resolved by gel electrophoresis into two components, termed alpha glycoprotein and beta-glycoprotein, with Mr values (nonreduced) of 46,000 and 42,000, respectively. Each was comprised of fewer and more neutral charge isomers than ZP3. Following purification by reverse phase high performance liquid chromatography, the alpha- and beta-glycoproteins of endo-beta-galactosidase digested ZP3 were distinguished on the basis of amino acid and carbohydrate compositions, amino-terminal sequence analyses and peptide mapping experiments, thus suggesting differences in the primary structures of their respective polypeptide moieties. Corresponding dissimilarities in the immunoreactivities of the alpha- and beta-glycoproteins toward polyclonal antisera raised against ZP3, alpha-glycoprotein, and beta-glycoprotein were revealed by competitive binding radioimmunoassays as well as by immunoblotting experiments. Collectively, the data were interpreted to indicate that the Mr = 55,000 antigen of porcine oocyte zona pellucida is in fact comprised of overlapping families of charge isomers corresponding to two structurally and immunologically distinct lactosaminoglycan containing glycoproteins. PMID- 3100515 TI - Rat liver NAD(P)H: quinone reductase nucleotide sequence analysis of a quinone reductase cDNA clone and prediction of the amino acid sequence of the corresponding protein. AB - We have determined the nucleotide sequence of a cDNA clone, pDTD55, complementary to rat liver quinone reductase mRNA (Williams, J.B., Lu, A.Y.H., Cameron, R.G., and Pickett, C.B. (1986) J. Biol. Chem. 261, 5524-5528). The cDNA clone contains an open reading frame of 759 nucleotides encoding a polypeptide comprised of 253 amino acids with a Mr = 28,564. To verify the predicted amino acid sequence of quinone reductase, we have been able to align the amino acid sequences of a cyanogen bromide digest of the purified enzyme to the sequence deduced from the cDNA clone. A comparison of the quinone reductase sequence with other known flavoenzymes did not reveal a significant degree of amino acid sequence homology. These data suggest that the quinone reductase gene has evolved independently from genes encoding other flavoenzymes. PMID- 3100516 TI - The presence of free G protein beta/gamma subunits in human neutrophils results in suppression of adenylate cyclase activity. AB - We have examined the adenylate cyclase of human neutrophil membranes and compared it to that of human platelet membranes. Stimulated activities were at least 20 fold lower in the neutrophil than in the human platelet. The inhibitory hormone epinephrine was able to attenuate markedly the adenylate cyclase activity of human platelets at micromolar concentrations, whereas little inhibition was observed in the human neutrophil at up to 100 microM concentrations. When we examined the ability of exogenous pure beta/gamma subunits to affect adenylate cyclase activity in both systems, we observed dose-dependent inhibition of stimulated adenylate cyclase activities in the platelet, whereas no inhibition of neutrophil adenylate cyclase could be detected. This difference did not appear to be due to differences in the degree of incorporation of beta/gamma into each membrane. The effects of G protein alpha subunits were also examined. In the platelet, unliganded G protein alpha produced an increase in adenylate cyclase activity of limited extent which saturated at relatively low levels of alpha subunit. In the neutrophil, the effect of unliganded G protein alpha did not appear to saturate and produced much larger relative increases in adenylate cyclase activity. Quantitation of the free beta/gamma activity in neutrophil extracts detected free beta/gamma activity even in the absence of G protein activators. We hypothesize the human neutrophil to be a system in which an excess of free beta/gamma subunits is present and which suppresses neutrophil adenylate cyclase activity. This excess of free beta/gamma minimizes any additional effect of exogenous beta/gamma, but can be reversed by addition of proteins which can bind beta/gamma subunits, e.g. G alpha subunits. PMID- 3100517 TI - Tissue factor (coagulation factor III) inhibition by apolipoprotein A-II. AB - Apolipoprotein A-II (apoA-II) has been shown to inhibit tissue factor participation in the activation of coagulation factor X by factor VIIa. The magnitude of inhibition was dependent on the concentration of the enzyme (factor VIIa) and substrate (factor X) present in the reaction. With factor VIIa at 0.86 nM, 0.41 microM apoA-II inhibited factor X activation as much as 50% at 200 nM factor X, with inhibition decreasing to 39% at 3 nM factor X. When factor X was held constant at 100 nM, 0.41 microM apoA-II inhibited its activation by 80% when factor VIIa was present at 26.7 pM, but the inhibition decreased to 47% when factor VIIa was increased to 1.75 nM. Kinetically, increasing apoA-II decreased the reaction Vmax. ApoA-II produced little effect on the apparent Km, but the apparent K1/2 for factor VIIa in the reaction increased as apoA-II concentration increased. In the presence of 0.75 pM bovine tissue factor, reconstituted with 4.31 microM phosphatidylserine-phosphatidylcholine (30:70, w/w) vesicles, and in the absence of apoA-II, the apparent Km was near 7 nM factor X when factor VIIa was present at 0.86 nM. Under the same conditions with factor X at 100 nM, the apparent K1/2 was near 56 pM factor VIIa. As apoA-II was added to 0.41 microM, the apparent K1/2 increased to about 200 pM factor VIIa. The aggregate results support a model in which apoA-II inhibits tissue factor potentiation of factor VIIa activity. Because the apparent K1/2 increases when apoA-II is added, the factor VIIa can apparently protect tissue factor from the effects of apoA-II. Thus, apoA-II appears to inhibit factor X activation by preventing the appropriate association of tissue factor with factor VIIa. PMID- 3100518 TI - The effect of activating ligands on the intrinsic fluorescence of guanine nucleotide-binding regulatory proteins. AB - The intensity of the tryptophan fluorescence of the alpha subunits of guanine nucleotide-binding regulatory proteins increases when they bind guanosine 5'-O-(3 thio)triphosphate (GTY gamma S). The kinetics of the fluorescence enhancement and of the measured binding of [35S]GTP gamma S are well correlated. The addition of Mg2+ to the nucleotide-bound proteins causes a further, rapid increase in the fluorescence intensity. Similar effects result from exposure of the proteins to F and Mg2+, and the required concentration of F- is reduced by the inclusion of Al3+. It is presumed that the more highly fluorescent state of the G protein alpha subunits represents their active conformation. PMID- 3100519 TI - Effects of Mg2+ and the beta gamma-subunit complex on the interactions of guanine nucleotides with G proteins. AB - Mg2+ interacts with the alpha subunits of guanine nucleotide-binding regulatory proteins (G proteins) in the presence of guanosine-5'-[gamma-thio]triphosphate (GTP-gamma S) to form a highly fluorescent complex from which nucleotide dissociates very slowly. The apparent Kd for interaction of G alpha X GTP gamma S with Mg2+ is approximately 5 nM, similar to the Km for G protein GTPase activity X G beta gamma increases the rate of dissociation of GTP gamma S from G alpha X GTP gamma S or G alpha X GTP gamma S X Mg2+ at low concentrations of Mg2+. When the concentration of Mg2+ exceeds 1 mM, G beta gamma dissociates from G beta gamma X G alpha X GTP gamma S X Mg2+. Compared with the dramatic effect of Mg2+ on binding of GTP gamma S to G alpha, the metal has relatively little effect on the binding of GDP. However, G beta gamma increases the affinity of G alpha for GDP by more than 100-fold. High concentrations of Mg2+ promote the dissociation of GDP from G beta gamma X G alpha X GDP, apparently without causing subunit dissociation. The steady-state rate of GTP hydrolysis is strictly correlated with the rate of dissociation of GDP from G alpha under all conditions examined. Thus, there are at least two sites for interaction of Mg2+ with G protein-nucleotide complexes. Furthermore, binding of G beta gamma and GTP gamma S to G alpha is negatively cooperative, while the binding interaction between G beta gamma and GDP is strongly positive. PMID- 3100520 TI - The influence of basic residues on the substrate specificity of protein kinase C. AB - The substrate specificity of protein kinase C has been examined using a series of synthetic peptide analogs of glycogen synthase, ribosomal protein S6, and the epidermal growth factor receptor. The glycogen synthase analog peptide Pro1-Leu Ser-Arg-Thr-Leu-Ser-Val-Ala-Ala10 was phosphorylated at Ser7 with a Km of 40.3 microM. Peptide phosphorylation was strongly dependent on Arg4. When lysine was substituted for Arg4 the Km was increased approximately 20-fold. Addition of basic residues on either the NH2-terminal or COOH-terminal side of the phosphorylation site of the glycogen synthase peptide improved the kinetics of peptide phosphorylation. The analog Pro-Leu-Ser-Arg-Thr-Leu-Ser-Val-Ala-Ala-Lys Lys was phosphorylated with a Km of 4.1 microM. Substitution of Ser7 with threonine increased the apparent Km to 151 microM. The truncated peptide Pro1-Leu Ser-Arg-Thr-Leu-Ser-Val8 was phosphorylated with similar kinetic constants to the parent peptide, however, deletion of Val8 increased the apparent Km to 761 microM. The ribosomal peptide S6-(229-239) was phosphorylated with a Km of approximately 0.5 microM predominantly on Ser236 and is one of the most potent synthetic peptide substrates reported for a protein kinase. The apparent Km for S6 peptide phosphorylation was increased by either deletion of the NH2-terminal 3 residues Ala229-Arg-231 or by substitution of Arg238 on the COOH-terminal side of the phosphorylation site with alanine. This analog peptide, [Ala238]S6-(229-239) was phosphorylated with an approximate 6-fold reduction in Vmax and a switch in the preferred site of phosphorylation from Ser236 to Ser235. These results support the concept that basic residues on both sides of the phosphorylation site can have an important influence on the kinetics of phosphorylation and site specificity of protein kinase C. PMID- 3100521 TI - Nearest neighbor analysis for brain synapsin I. Evidence from in vitro reassociation assays for association with membrane protein(s) and the Mr = 68,000 neurofilament subunit. AB - Synapsin I, a major neuron-specific substrate for cAMP-dependent and Ca2+/calmodulin-dependent protein kinases, associates in in vitro assays with brain integral membrane protein site(s) distinct from secretory vesicles and with the neurofilament Mr = 68,000 subunit. The membrane sites for synapsin involve protein(s) and are likely to have physiological relevance since the binding of 125I-labeled synapsin is abolished by digestion with chymotrypsin, is displaced by unlabeled synapsin, is of high affinity (KD = 10 nM), and has a capacity (42 pmol/mg membrane protein) that is comparable to the amount of synapsin in brain, optimal binding occurs at physiological pH (6.8-7.2) and salt concentrations (50 mM), and synapsin binding to membranes is inhibited by phosphorylation with Ca2+/calmodulin-dependent protein kinase. The brain membrane protein sites for synapsin are not due to synaptic vesicles, since synaptic vesicles do not sediment under the conditions of the binding assay. Association between synapsin and the Mr = 68,000 neurofilament subunit has also been demonstrated. The binding of synapsin with the neurofilament subunit is specific since this binding interaction is saturable, with a 1:1 stoichiometry, the binding involves only certain proteolytically derived domains of synapsin, and is therefore not a simple electrostatic interaction between the basic domains of synapsin and the acidic regions in the neurofilament subunit, and Ca2+/calmodulin-dependent phosphorylation of synapsin inhibits this interaction. Synapsin promotes cross linking of synaptic vesicles to brain membranes, and these complexes are reduced by phosphorylation of synapsin. This interconnecting function of synapsin may be a general characteristic of synapsin binding, with a membrane (synaptic vesicle or nonsecretory vesicle)-bound synapsin associating with microtubules, neurofilaments, or spectrin. PMID- 3100522 TI - Heavy riboflavin synthase of Bacillus subtilis. Primary structure of the beta subunit. AB - Heavy riboflavin synthase is a 1,000,000-Da protein catalyzing the last two reactions of riboflavin biosynthesis. The enzyme complex consists of 60 beta subunits (Mr = 16,200) and approximately three alpha subunits (Mr = 23,000). beta subunits were isolated and cleaved with cyanogen bromide. Fragments were isolated and further digested with trypsin and staphylococcal protease. Peptides were isolated by high performance liquid chromatography. Sequences were determined by automated liquid-phase Edman degradation. The complete sequence of the beta subunit (154 amino acids) was established by direct sequencing of the NH2 terminus, sequencing of overlapping peptides, and carboxypeptidase degradation of the COOH terminus. The sequence shows no detectable homologies to other proteins. A computer prediction of secondary structure elements indicates 34% alpha helix and 30% beta sheet. PMID- 3100523 TI - Amino acid sequence of a novel calmodulin from Paramecium tetraurelia that contains dimethyllysine in the first domain. AB - A class of Paramecium behavioral mutants called pantophobiacs have a deficiency in calcium-dependent potassium efflux, and this deficiency can be corrected by the microinjection of wild-type Paramecium calmodulin (Hinrichsen, R. D., Burgess Cassler, A., Soltvelt, B. C., Hennessey, T., and Kung, C. (1986) Science 232, 503 506). As a starting point in investigations of which features allow wild-type Paramecium calmodulin to fully restore this behavior while other calmodulins are inactive or poorly effective, we elucidated the amino acid sequence of the wild type calmodulin. We utilized an approach that combined Edman chemistry with mass spectrometry. This approach resulted in the identification of a new post translational modification in calmodulin: N epsilon,N epsilon-dimethyllysine at residue 13. This particular modification has not been described for calmodulins studied previously. The only other first-domain modification that has been described for any calmodulin is acetylation of the amino terminus (Watterson, D. M., Sharief, F., and Vanaman, T. C. (1980) J. Biol. Chem. 255, 962-975). These results along with analyses of pantophobiac calmodulin and calmodulin binding proteins will provide insight into calmodulin's role in a well-defined behavioral mutant. PMID- 3100524 TI - Amino-terminal processing of proteins by N-myristoylation. Substrate specificity of N-myristoyl transferase. AB - Using synthetic octapeptides, we examined the amino-terminal sequence requirements for substrate recognition by myristoyl-CoA:protein N-myristoyl transferase (NMT). NMT is absolutely specific for peptides with amino-terminal Gly residues. Peptides with Asn, Gln, Ser, Val, or Leu penultimate to the amino terminal Gly were substrates, whereas peptides with Asp, D-Asn, Phe, or Tyr at this position were not myristoylated. Peptides with aromatic residues at this position competitively inhibited myristoylation of substrates, introducing the possibility of developing specific in vivo inhibitors of NMT. Peptides having sequences which correspond to those of known N-myristoyl proteins, including p60src, appear to be recognized by a single enzyme, and yeast and murine NMT have identical substrate specificities. The catalytic selectivity of NMT for myristoyl transfer accounts for the remarkable acyl chain specificity of this enzyme. PMID- 3100525 TI - Equilibrium binding of derivatives of the carcinogen, benzo(a)pyrene, to DNA. Thermodynamic analysis. AB - The physical binding of polycyclic aromatic hydrocarbon derivatives which are ultimate carcinogens to DNA may play a role in the formation of covalent DNA adducts by these compounds or in the detoxification of the compounds via DNA catalyzed hydrolysis. Previous studies of DNA-binding interactions of derivatives of benzo(a)pyrene (BP) have been confined to low r values (r - ligands bound/base pair). We have now applied the Scatchard formalism (as modified to include neighbor exclusion) to the spectrophotometric determination of the binding of two derivatives of BP, trans - 9,10 - dihydroxydihydro - BP and 7r,8t - dihydroxy 9t,10t-oxy-7,8, 9,10-tetrahydro-BP, to double-stranded DNA at reasonably high r values. Exclusion parameters, binding constants, and thermodynamic parameters are all within the ranges found for other intercalants. Although these ligands are uncharged, the binding exhibits significant ionic strength dependence which can be rationalized (partially) by polyelectrolyte theory. Using the measured ionic strength dependence, a thermodynamic association constant, independent of ionic interactions, can be calculated which is very close to the calculated thermodynamic association constants for ethidium and proflavine. PMID- 3100526 TI - Implication of histidine at the active site of exo-beta-(1-3)-D-glucanase from Basidiomycete sp. QM 806. AB - The enzyme, exo-beta-(1-3)-D-glucanase, (EC 3.2.1-) obtained from a culture filtrate of Basidiomycete sp. QM 806, has been obtained in a highly purified form and preliminary investigations on its mechanism of action have been reported (Peterson, D. R., and Kirkwood, S. (1975) Carbohydr. Res. 41, 273-283). Studies reported in this paper, have provided strong evidence for the role of histidine in the catalytic site of this carbohydrase. Chemical modifications of the amino acid residues in the enzyme with diazotized 5-amino-1H-tetrazole or tetranitromethane caused irreversible loss of enzyme activity which varied according to the time of exposure to, or concentration of the inhibitor. Prior incubation of the enzyme with a substrate considerably reduced the extent of this inhibition. Amino acid analysis of the enzyme treated in these ways clearly indicated that the substrate protected histidine residues from chemical modification by the diazotized 5-amino-1H-tetrazole. Chemical modification of both histidine and tyrosine residues were effected by incubating the enzyme with the inhibitors described above. Although evidence is presented to suggest that tyrosine is not directly involved in the active site of the enzyme (the catalytic site or the binding site), the role of this residue in the maintenance of the enzyme conformation is discussed. Enzyme assays carried out either in aqueous or deuterated buffer systems provided further evidence which is consistent with the proposed enzyme mechanism. PMID- 3100527 TI - Regulation of basal and insulin-stimulated glycogen synthesis in cultured hepatocytes. Inverse relationship to glycogen content. AB - Cultured rat hepatocytes were used to characterize the relationship between cellular glycogen content and the basal rate, as well as response to insulin of glycogen synthesis. Depending on the concentration of medium glucose, glycogen depleted monolayers accumulated glycogen between 24 and 48 h of culture up to the fed in vivo level. Insulin at 100 nM stimulated glycogen deposition 20-fold at 1 mM and 1.5-fold at 50 mM glucose. The rate of further glycogen storage decreased with time and increasing glycogen content. In hepatocytes preincubated with 1-50 mM glucose during 24-48 h, short-term basal and insulin-dependent incorporation of 10 mM [14C]glucose into glycogen was inversely related to the actual cellular glycogen content. This was not due to different intracellular dilution of the label, since the specific radioactivity of UDP-glucose was similar in all groups. 125I-Insulin binding indicated that insulin receptors were also not involved in this phenomenon. An inverse relationship was also found between glycogen content and the stimulation of glycogen synthase I activity by insulin, whereas the basal activity of the enzyme was dissociated from the rate of incorporation of [14C]glucose. Basal net glycogen deposition at 10 mM glucose was also inversely related to cellular glycogen; however, no such relation was evident in the presence of insulin due to the overlapping inhibition of glycogenolysis. These studies suggest that the glycogen-mediated inhibition of the activation of glycogen synthase I is operative in the cultured hepatocyte and leads to an apparent inverse relationship between the actual glycogen content and basal as well as insulin-dependent glycogenesis. PMID- 3100528 TI - The enzymatic mechanism of glucuronidation catalyzed by two purified rat liver steroid UDP-glucuronosyltransferases. AB - A kinetic analysis of two homogeneous rat liver steroid (3 alpha-hydroxysteroid and 17 beta-hydroxysteroid) UDP-glucuronosyltransferases was conducted using bisubstrate kinetic analysis, product inhibition studies, and dead-end competitive inhibition studies. Double reciprocal plots of initial velocity versus substrate concentration, using bisubstrate kinetic analysis, gave a sequential mechanism. Product inhibition studies were compatible with either a rapid equilibrium, random-order kinetic mechanism or an ordered Theorell-Chance mechanism. Results of dead-end competitive inhibition studies excluded an ordered Theorell-Chance mechanism. The cumulative results are consistent with a rapid equilibrium random-order sequential kinetic mechanism for the glucuronidation of testosterone by purified 17 beta-hydroxysteroid UDP-glucuronosyltransferase and of androsterone by purified 3 alpha-hydroxysteroid UDP-glucuronosyltransferase. PMID- 3100529 TI - A nuclear specific glycoprotein representative of a unique pattern of glycosylation. AB - Whole rat liver nuclei were reacted with UDP-[14C]galactose in the presence of bovine beta(1----4) galactosyltransferase. The reaction mixture was electrophoresed on a reducing sodium dodecyl sulfate-polyacrylamide gel. Autoradiograms of the gel demonstrated a major labeled broad band migrating with an apparent molecular weight of 65,000-66,000. A number of other less prominently labeled bands were also present. The labeled 65,000-66,000 band when cut from the gel and subjected to alkaline reduction while in the gel matrix exclusively yielded a 14C-labeled disaccharide that co-migrated with a [14C]Gal-GlcNAcol standard in descending paper chromatography. Treatment of this disaccharide with beta-galactosidase (beta-D-galactoside galactohydrolase; EC 3.2.1.23) from Aspergillus niger removed all the [14C]galactose label. Treatment of the labeled 65,000-66,000 polypeptide with Endoglycosidase F, however, did not remove the [14C]galactose label. Western transfer blots of sodium dodecyl sulfate polyacrylamide gel electrophoresis gels performed with horseradish peroxidase labeled succinyl wheat germ agglutinin, a lectin specific for GlcNAc, on unlabeled nuclei revealed a dominant band at 63,000-64,000. Subjecting 14C labeled nuclei to this procedure resulted in a shift of the major horseradish peroxidase-labeled succinyl wheat germ agglutinin band to 65,000-66,000. The shifted band was coincident with the [14C]galactose band as visualized on an autoradiogram. A survey of other rat tissue nuclei revealed the same spectrum of [14C]galactose acceptor proteins with a dominant 65,000-66,000 galactose-labeled band. PMID- 3100530 TI - Phosphorylation of serine 833 in cytoplasmic domain of low density lipoprotein receptor by a high molecular weight enzyme resembling casein kinase II. AB - A soluble protein kinase that phosphorylates the last serine residue (Ser-833) in the cytoplasmic domain of the low density lipoprotein (LDL) receptor was purified about 1300-fold from the cytosol of bovine adrenal cortex. The LDL receptor kinase shared several properties with casein kinase II: use of either GTP or ATP; phosphorylation of a typical casein kinase II recognition sequence in the LDL receptor (a serine followed by a cluster of three negatively charged amino acids); and inhibition by heparin. The LDL receptor kinase differed from classic casein kinase II in the following respects: its apparent molecular weight on gel filtration was approximately 500,000 as opposed to the usual molecular weight of 130,000 for casein kinase II; its affinity for the LDL receptor (apparent Km approximately 5 nM) was much greater than its affinity for casein (approximately 10 microM); and its activity was inhibited by polylysine, an agent that stimulates casein kinase II. The physiologic role of this unusual kinase, if any, is unknown. PMID- 3100531 TI - Immunochemical and kinetic evidence for two different prostaglandin H prostaglandin E isomerases in sheep vesicular gland microsomes. AB - Splenic lymphocytes from mice immunized with a partially purified prostaglandin (PG) H-PGE isomerase from sheep vesicular glands were fused with SP2/0-Ag14 myeloma cells. Two spleen cell-myeloma hybrids (hei-7 and hei-26) were selected and cloned. The mouse antibodies secreted by the two hybrids, IgG1 (hei-7) and IgG1 (hei-26), caused immunoprecipitation of a maximum of 45 and 22%, respectively, of the solubilized PGH-PGE isomerase activity of sheep vesicular gland; immunoprecipitation of activity by the two antibodies was additive. The antigens reactive with IgG1 (hei-7) and IgG1 (hei-26) were identified as proteins with Mr = 17,500 and 180,000, respectively, by Western transfer blotting or sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoprecipitated 125I-labeled microsomes. The PGH-PGE isomerase activities precipitated by IgG1 (hei-7) and IgG1 (hei-26) exhibited different kinetic properties with respect to time course, Km for PGH2, and concentration dependence for GSH. No significant GSH-S-transferase activity was present in these immunoprecipitates. These data indicate that there are at least two different proteins in sheep vesicular gland microsomes capable of catalyzing GSH-dependent PGH-PGE isomerase reactions. IgG1 (hei-7), but not IgG1 (hei-26), caused coprecipitation of PGH synthase and PGH PGE isomerase activities when incubated with intact right-side-out vesicular gland microsomes. Thus, the epitope for IgG1 (hei-7) is located on the cytoplasmic surface of those microsomal spheres which contain PGH synthase. This latter finding suggests that the isomerase reactive with IgG1 (hei-7) is involved in PGE synthesis in sheep vesicular glands. PMID- 3100532 TI - The 1- and 2-electron oxidation of acetaminophen catalyzed by prostaglandin H synthase. AB - Purified and microsomal preparations of prostaglandin H synthase catalyzed the arachidonic acid-dependent polymerization of acetaminophen and, in the presence of GSH, catalyzed the formation of 3-(glutathion-S-yl)acetaminophen. The formation of these products was inhibited by indomethacin and by purging reaction mixtures with argon. When H2O2 replaced arachidonic acid, neither indomethacin nor argon purging inhibited product formation. These results suggest that the peroxidase activity of prostaglandin H synthase catalyzed the oxidation of acetaminophen. Addition of GSH to reaction mixtures decreased acetaminophen polymerization; however, 3-(glutathion-S-yl)acetaminophen formation was maximal with 40 microM GSH, and higher concentrations of GSH did not substantially alter its formation. In the presence of GSH, either ascorbic acid or NADPH decreased polymerization by greater than 97% while 3-(glutathion-S-yl)acetaminophen formation was still observed. These data suggest that polymers and conjugates were formed by two different pathways. Since polymerization of acetaminophen involves radical termination of N-acetyl-p-benzosemiquinone imine whereas 3 (glutathion-S-yl)acetaminophen is formed by conjugation of N-acetyl-p benzoquinone imine with GSH, the data suggest that prostaglandin H synthase catalyzed both the overall 1- and 2-electron oxidation of acetaminophen. PMID- 3100534 TI - The amino acid sequence of rhizopuspepsin, an aspartic proteinase from Rhizopus chinensis. AB - The complete amino acid sequence of rhizopuspepsin, an aspartic proteinase from the fungus Rhizopus chinensis was determined by conventional protein sequencing, using peptide fragments obtained mainly by several enzymatic cleavages of the reduced and carboxymethylated (RCm-) protein. The RCm-protein was first cleaved by trypsin, and the resulting peptides were purified and their amino acid sequences determined extensively. These tryptic peptides were aligned by the aid of overlapping peptides isolated from a tryptic and a chymotryptic digest of the citraconylated RCm-protein and the RCm-protein, respectively. The amino acid sequence thus deduced was further confirmed by isolation and sequence determination of peptides obtained by digestion of the RCm-protein with Staphylococcus aureus V8 protease. The location of the disulfide bonds was determined by isolation and analysis of cystine-containing peptides from a chymotryptic digest of intact rhizopuspepsin. These results showed that the protein is composed of a single polypeptide chain of 325 amino acid residues cross-linked by two disulfide bonds, and shows overall homology with other aspartic proteinases, including 36% identity with penicillopepsin and 38% identity with porcine pepsin. PMID- 3100533 TI - Induction of the fibrinogen receptor on human platelets by intracellular mediators. AB - We have used platelets permeabilized with saponin to examine the mechanism by which platelet activation causes the exposure of surface receptors for fibrinogen. Receptor exposure was detected using 125I-fibrinogen and 125I-PAC1, a monoclonal antibody specific for the activated form of the fibrinogen receptor. The potential mediators that were studied included guanyl-5'-yl imidodiphosphate (Gpp(NH)p) and guanosine 5'O-(thiotriphosphate) (GTP gamma S), which cause G protein-dependent phospholipase C activation in platelets; inositol 1,4,5 triphosphate (IP3), which causes Ca2+ release from the platelet dense tubular system; and diacylglycerol and phorbol ester, which activate protein kinase C. Each of these molecules caused fibrinogen and PAC1 binding. The effect of IP3 was mimicked by raising the cytosolic free Ca2+ concentration in the permeabilized platelets. However, IP3 and Ca2+-induced PAC1 binding were abolished by indomethacin or aspirin, which had no effect on PAC1 binding caused by Gpp(NH)p, phorbol ester, or diacylglycerol. This suggests that the response to IP3 and Ca2+ is due to the formation of metabolites of arachidonic acid. One such metabolite, TxA2, is believed to activate platelets by stimulating G protein-dependent phosphoinositide hydrolysis. Indeed, we found that the G protein inhibitor guanyl 5'-yl thiophosphate (GDP beta S) inhibited PAC1 binding caused by a thromboxane A2 analog (U46619), IP3, and Ca2+, but had no effect on diacylglycerol or phorbol ester-induced PAC1 binding. Thrombin-induced PAC1 binding and phosphoinositide hydrolysis were also inhibited by GDP beta S and by pertussis toxin. Increasing the thrombin concentration overcame the inhibition of PAC1 binding caused by GDP beta S but did not overcome the inhibition of phosphoinositide hydrolysis. These observations demonstrate that fibrinogen receptor exposure occurs by at least two routes. One of these, in response to agonists such as thrombin and U46619, is initiated by G protein-dependent phosphoinositide hydrolysis and involves the formation of IP3 and diacylglycerol. IP3 appears to act by stimulating Ca2+ dependent arachidonic acid metabolism which, in turn, triggers further phosphoinositide hydrolysis. Diacylglycerol acts by stimulating protein kinase C. A second route is activated by high concentrations of thrombin and is independent of phosphoinositide hydrolysis. PMID- 3100535 TI - Solid-state NMR studies of regulation of N-(phosphonomethyl)glycine and glycine metabolism in Pseudomonas sp. strain PG2982. AB - Lyophilized samples of Pseudomonas sp. PG2982 grown on 13C- and 15N-labeled glyphosate have been analyzed by single and double cross-polarization 13C NMR. Both the carbon and nitrogen metabolism of glyphosate are significantly influenced by the nitrogen source used for the growth of the organism. When ammonium sulfate is the source of nitrogen, the glycyl moiety of glyphosate is utilized intact for the biosynthesis of purines and proteins. But when the organism is grown on glycine as the source of nitrogen, the carbons and nitrogen of glyphosate are scrambled, consistent with incorporation into serine and pyruvate, and hence participation in general metabolism. When both ammonium and glycine are present in the growth medium, regulation of the metabolic fluxes along each of the two major pathways appears to be determined by the intracellular glycine concentration. PMID- 3100536 TI - A heparin-binding domain of human von Willebrand factor. Characterization and localization to a tryptic fragment extending from amino acid residue Val-449 to Lys-728. AB - We have recently shown that the domain of von Willebrand factor (vWF) which interacts with the platelet glycoprotein Ib (GPIb) is located in a 52/48-kDa tryptic fragment of the molecule which begins with amino acid residue Val-449. We have now established that the fragment extends to residue Lys-728 and demonstrate here that a high affinity heparin-binding domain of vWF also lies within this region and in close proximity to that for GPIb. We have used an assay employing heparin coupled to Sepharose CL-6B to show that 125I-vWF binds to heparin in a time-dependent, saturable, and reversible manner. Binding could be completely inhibited by the 52/48-kDa fragment, but was not affected by other tryptic fragments of 55, 41, 13, and 22 kDa. NH2-terminal sequencing of these fragments showed that they were derived from different parts of the molecule, as follows: 13 kDa, Gln290-Thr-Met-Val-Asp-Ser-Ser; 55 kDa, Asn730-Ser-Met-Val-Leu-Asp-Val Ala-Phe-Val-Leu-Glu; 41 kDa, Thr1352-Val-Gln-Arg-Pro-Gly-Gln-Thr-Cys-Gln-Pro-Ile Leu-Glu-Glu-Gl n-Cys-Leu-Val ; 22 kDa, Val1927-Thr-Gly-Cys-Pro-Pro. Direct binding of the purified 52/48-kDa fragment to heparin-Sepharose was also shown. Furthermore, crossed immunoelectrophoresis revealed complex formation between the purified 52/48-kDa fragment and free heparin. Twelve monoclonal antibodies to the 52/48-kDa fragment were evaluated for their ability to block binding of 125I-vWF to heparin. With the exception of one weak inhibitor of heparin binding, their relative efficacy in blocking heparin binding was similar to that for blocking ristocetin-induced binding to GPIb. However heparin failed to block ristocetin independent binding of the 52/48-kDa fragment to GPIb. It is therefore likely that the two binding domains are adjacent to one another, but are not precisely congruent. PMID- 3100538 TI - Scheuermann kyphosis. Follow-up of Milwaukee-brace treatment. AB - From 1960 through 1978, a total of 274 patients who had a diagnosis of Scheuermann kyphosis were treated with a Milwaukee brace at the Twin Cities Scoliosis Center. We analyzed the long-term results in 120 patients who had used the Milwaukee brace and had been followed for at least five years after the completion of treatment. The average age of the patients at the initiation of treatment was twelve years and five months, the average age at the completion of treatment was sixteen years and one month, and the average age at the last follow up examination was twenty-four years. Of the patients who wore the brace consistently, seventy-six showed improvement in the kyphosis between the initial evaluation and the evaluation at final follow-up, while twenty-four showed worsening and ten were unchanged. Seven of the twenty-four patients who were worse had had surgery before the review for this study. The indication for surgery was a kyphosis of more than 60 degrees that was increasing and was not controlled by the brace. Ten patients were inconsistent in their use of the brace. Two of the ten patients had improvement and eight had worsening of the kyphosis; three of the latter eight had a spinal fusion. This study showed that the Milwaukee brace is usually an effective method of treatment for patients who have Scheuermann kyphosis; however, four of fourteen patients who had an initial kyphosis of more than 74 degrees required a spinal fusion. PMID- 3100537 TI - Human insulin receptors mutated at the ATP-binding site lack protein tyrosine kinase activity and fail to mediate postreceptor effects of insulin. AB - Transfected Chinese hamster ovary cell lines were developed that expressed equivalent numbers of either normal human receptor or receptor that had alanine substituted for Lys-1018 in the ATP-binding domain of the beta subunit. The mutated receptor was processed into subunits and bound insulin but lacked protein tyrosine kinase activity. Five effects of insulin were assayed: deoxyglucose uptake, S6 kinase activity, endogenous protein-tyrosine phosphorylation, glycogen synthesis, and thymidine uptake. In each case, cells bearing normal human receptors were 10-100-fold more sensitive to insulin than the parental cells. Cells with the mutant receptor behaved like the parental cells with respect to S6 kinase activation, endogenous substrate phosphorylation, glycogen synthesis, and thymidine uptake, but their deoxyglucose uptake was significantly depressed and relatively insensitive to insulin. The analyses led to the following conclusions: substitution of alanine for lysine at amino acid 1018 inactivates the kinase activity of the receptor; a kinase-negative receptor can be properly processed and bind insulin; insulin-dependent deoxyglucose uptake, S6 kinase activation, endogenous substrate phosphorylation, glycogen synthesis, and thymidine incorporation into DNA are mediated by the normal but not by the kinase-deficient human receptor. PMID- 3100540 TI - Carbonic anhydrase cytochemistry in mitochondria-rich cells of salamander larvae gill epithelium as related to age and H+ and Na+ concentrations. AB - Carbonic anhydrase (CAH) was localized in the mitochondria-rich cells (MRC) of 1 week-old salamander larvae gill epithelium, in both MRC and pavement cells of 6 week-old larvae, and in regenerated stems of previously amputated gills. CAH activity of the MRC was measured quantitatively using a microscope densitometric technique. Changes in CAH activity per cell and changes in the numbers of CAH positive MRC were followed under different H+ and Na+ concentrations at the two age groups. CAH activity per cell increased with age, whereas the numbers of CAH positive MRC dropped. CAH activity per cell in the 1-week-old age group reached maximal values at pH 7.4 and stayed relatively high in the more alkaline media. Moderate increases of Na+ concentrations had small but significant effects on increasing CAH activity of gill MRC. When taking into consideration not only the changes in cellular activity but also the changes in the number of CAH-positive cells under the different acclimation media, an activity index (ICAH) was calculated. Thus, the ICAH in the 1-week-old was found to be dependent on the decline of ambient H+ concentrations (expressed as increasing pH), reaching maximal effect at pH 8.0. On the other hand, raising the Na+ concentrations of the acclimation media to 110 and 220 mOsm/liter caused a maximal inhibition of tissue CAH activity as expressed by ICAH. In conclusion, it is suggested that salamander larvae gill MRC take part in the adaptation of the larvae to changing H+ concentrations of their milieu rather than in their adaptation to changes in its osmolality. PMID- 3100539 TI - Elaboration of neutral proteoglycanase by growth-plate tissue cultures. AB - This report describes the properties of a neutral protease that was synthesized and secreted into medium by intact cartilaginous growth plate in tissue culture. Bovine cartilaginous growth plate was grown for seven days in tissue culture, during which time the chondrocytes remained viable and metabolically active as determined by quantitation of trypan-blue exclusion and incorporation of 3H cytidine. Protease activity, assayed by viscometry using proteoglycan monomer from cartilage as a substrate, was absent on day 1 but was present at high levels on days 2 through 5. The protease activity did not require activation and was highest at neutral and alkaline pH. Protease activity was abolished by twenty millimolar EDTA but was unaffected by pepstatin, iodoacetate, and soybean trypsin inhibitor. In contrast to the high levels of activity of neutral protease that were present in tissue cultures of the intact growth plate, no protease activity could be detected when chondrocytes from the cartilaginous growth plate were grown in cell culture, even after sonication of the cells or activation with aminophenyl mercuric acetate or trypsin. Since hypertrophic chondrocytes probably do not survive the disruption of tissue that is involved in establishing cell cultures, these observations suggest that neutral protease is probably released into the medium by the hypertrophic chondrocytes that are present in the cultures of cartilaginous growth-plate tissue. It appears that the organization of the growth plate in tissue culture, as well as the maturation of proliferating chondrocytes into hypertrophic chondrocytes in tissue culture, may be required for synthesis of the neutral protease and its extracellular secretion by hypertrophic chondrocytes. PMID- 3100541 TI - Fibrinolytic system of cultured endothelial cells: regulation by plasminogen activator inhibitor. AB - Cultured bovine aortic endothelial cells have a relatively complex fibrinolytic system that is responsive to both the physiological state of the cell itself and to a variety of agents added to the culture medium. The fibrinolytic activity of these cells results from the production of both urokinase-type and tissue-type plasminogen activators and is regulated by an inhibitor capable of neutralizing their activities. The properties of these fibrinolytic components will be reviewed, and their respective roles in initiating and regulating the fibrinolytic activity of the cells will be summarized. A cDNA coding for the inhibitor has been isolated, and its sequence will be compared to that of other serine proteinase inhibitors. PMID- 3100543 TI - Examination of blood-brain barrier permeability in dementia of the Alzheimer type with [68Ga]EDTA and positron emission tomography. AB - Positron emission tomography with [68Ga]ethylenediaminetetraacetic acid ([68Ga]EDTA) was used to examine the integrity of the blood-brain barrier (BBB) in five patients with dementia of the Alzheimer type and in five healthy age matched controls. Within a scanning time of 90 min, there was no evidence that measurable intravascular tracer entered the brain in either the dementia or the control group. An upper limit for the cerebrovascular permeability-surface area product of [68Ga]EDTA was estimated as 2 X 10(-6) s-1 in both groups. The results provide no evidence for breakdown of the BBB in patients with dementia of the Alzheimer type. PMID- 3100542 TI - Chemotactic peptide-induced exocytosis in neutrophils: granule fusion patterns depend on the source of messenger calcium. AB - Rabbit neutrophils, exposed either to partially purified human C5a or to formylmethionyl-leucyl-phenylalanine in the presence of 5 micrograms ml-1 cytochalasin B underwent a rapid, compound exocytosis. The pattern of granule fusion, as visualized in freeze-fracture replicas, differed depending on the source of messenger calcium. In the presence of extracellular calcium, a linearly directed pattern, consisting of finger-like invaginations converging at the cell centre, was prominent at 10-20 s after stimulation. After stimulation for 20-40 s, further fusion of granule membranes created extremely convoluted surfaces, some consisting of up to a dozen granule membranes connected by narrow pores or flat ribbons of membrane. In many cells the peripheral cytoplasm was constricted to form lobes or finger-like protrusions. Neutrophils stimulated in the absence of extracellular calcium exhibited granule fusion in the directed pattern, with only occasional involvement of the convoluted patterns seen when calcium is present. In contrast, neutrophils depleted of intracellular calcium before stimulation (and thereby forced to use extracellular calcium for triggering secretion) exhibited the convoluted pattern of granule fusion almost exclusively. These results suggest that the directed pattern of fusion is initiated by release of intracellular calcium or a calcium-independent pathway and that the non directed, convoluted pattern of fusion is initiated by entry of extracellular calcium. PMID- 3100544 TI - Pial artery pressure after one hour of global ischemia. AB - Pial artery pressure was measured in anesthetized control cats and in animals subjected to 1 h of global ischemia and 6 h of recirculation. Cerebral blood flow (CBF) was measured with the intraarterial 133Xe technique before and after ischemia, and lumped segmental resistances upstream and downstream to the pial artery were calculated. In the control brain, upstream resistance was 1.30 +/- 0.28 and downstream resistance 0.94 +/- 0.1 mm Hg ml-1 100 g min. During the postischemic hypoperfusion period, both resistances significantly increased, indicating that hypoperfusion constitutes a dysregulation of both large extracerebral and small intracerebral vessels. Hypercapnia induced an increase of CBF in the control brain and was accompanied by a fall in downstream resistance, demonstrating intracortical vasodilation. By contrast, hypercapnia did not provoke changes in either CBF or segmental resistances in the hypoperfusion period. In conclusion, during the postischemic hypoperfusion period, both extra- and intracortical resistances are increased and vascular reactivity to CO2 is abolished. PMID- 3100545 TI - Effect of selective lesions of medullary catecholamine nuclei on experimental cerebral vasospasm in the rat. AB - Intracisternal injection of blood in the rat induces an angiographically demonstrable, biphasic cerebral vasospasm of the vertebrobasilar system, with a maximal acute spasm at 10 min and a maximal late spasm at 2 days after the subarachnoid hemorrhage (SAH). Selective lesioning of the A1 nuclei in the medulla oblongata prior to the SAH prevents the development of the late spasm, but the acute spasm develops to the same extent as in sham-lesioned animals. Lesions of the medullary A2 nuclei not only prevent the development of both acute and late spasm, but give rise to a dilatation of the vertebrobasilar arteries at day 2 post-SAH. The study indicates that both the A1 and A2 nuclei participate in the development of vasospasm post-SAH. The contrasting patterns of spasm after A1 and A2 lesions suggest a different mechanism for acute and late spasm. PMID- 3100547 TI - [Autotransplantation of islets of Langerhans in the rat using a new method of isolating the islets]. AB - The limiting factor of efficacy of islet of Langerhan's grafting for the treatment of diabetes is the number of islets available, the majority of isolation techniques used being chemical and wasteful. Animal studies have shown that 3 or 4 pancreases must be used to obtain a sufficient number of islets to correct an induced diabetes. A simple, totally mechanical method of their isolation was developed allowing a sufficient number of islets to be collected from a single pancreas for effective therapy of diabetes induced by total pancreatectomy in the rat. The same method can be applied to humans. PMID- 3100546 TI - Regional cerebral and neural lobe blood flow during insulin-induced hypoglycemia in unanesthetized rats. AB - The effects of hypoglycemia on regional cerebral blood flow (rCBF) were studied in awake restrained rats. The rats were divided into three groups consisting of a normoglycemic control group that received only saline, a hypoglycemic group A, which was given insulin 30 min before flow was measured, and a hypoglycemic group B, which was given insulin 90 and 30 min before flow was measured. Regional CBF was measured using 14C-iodoantipyrine. Mean plasma glucose was 8.76 mumol/ml in the control group, 2.63 mumol/ml in hypoglycemic group A, and 1.51 mumol/ml in hypoglycemic group B. Plasma epinephrine and norepinephrine concentrations increased to approximately 375% and 160%, respectively, of control values in hypoglycemic groups A and B. In the hypoglycemic group A, rCBF significantly increased in three brain regions. In the hypoglycemic group B, rCBF increased significantly in all brain regions measured, with the exception of the neural lobe, in which it decreased. The increase in rCBF ranged from 38% in the hypothalamus to 138% in the thalamus. Neural lobe blood flow significantly decreased by 31%. The neural lobe was the only brain region studied that is not protected by a blood-brain barrier. It may be sensitive to changes in the concentration of vasoactive agents in blood, such as epinephrine and norepinephrine. PMID- 3100548 TI - [Acute pancreatitis caused by lithiasis in a dilated ampulla of Vater]. AB - Unusual features in a case of dilatation of ampulla of Vater were in the existence of biliary calculi in the diverticulum and lithiasis complicated by a revealing acute pancreatitis. Diagnosis was suggested from barium meal followed through images and confirmed by perioperative cholangiography. Surgical treatment of such cases is simple, allows recovery without sequelae and avoids risks of recurrence. PMID- 3100550 TI - A Greek sailor with a hepatic mass. PMID- 3100549 TI - Lactase deficiency. Diagnosis and management. PMID- 3100551 TI - Pulmonary rehabilitation for COPD patients. PMID- 3100552 TI - Pernicious anemia that 'disappeared'. PMID- 3100553 TI - Current strategies in operable breast cancer. PMID- 3100554 TI - What is failing in respiratory failure? PMID- 3100555 TI - Cryoanalgesia: freezing of peripheral nerves. PMID- 3100556 TI - Itching as a manifestation of noncutaneous disease. PMID- 3100557 TI - Mini-mental state exam in clinical practice. PMID- 3100558 TI - Serologic evaluation of viral hepatitis. PMID- 3100559 TI - Magnesium deficiency: causes and effects. PMID- 3100560 TI - The emergence of biologicals as cancer treatment: the good news and the bad. PMID- 3100561 TI - Obesity: an eclectic review. PMID- 3100562 TI - Heritable defects in connective tissue. PMID- 3100563 TI - Hemochromatosis: current concepts and management. PMID- 3100564 TI - Semmelweis: Lone Rager against puerperal fever. PMID- 3100565 TI - The antigen that was heard but not 'seen'. PMID- 3100566 TI - An impaired physician. PMID- 3100567 TI - Pain syndromes in musicians. PMID- 3100568 TI - A 30-year-old woman with 70 hospitalizations. PMID- 3100569 TI - Angina pectoris and a slow bigeminal rhythm. PMID- 3100571 TI - High-performance chromatographic method for the purification of tissue-type plasminogen activator. AB - High-performance affinity chromatography was performed on five ligand-bound columns in an attempt to purify tissue-type plasminogen activator (t-PA), which is a glycoprotein with a high affinity for fibrin and also has two Kringle structures and finger-domain in its molecule. The five columns were concanavalin A-5PW, p-aminobenzamidine-5PW, imidinodiacetic acid-5PW, boric acid-5PW and lysine-5PW. All five were able to rapidly separate t-PA from contaminating proteins, with high resolution and recovery. PMID- 3100570 TI - Identification and assay of phosphoserine and tyrosine-O-sulphate in fibrinopeptides by reversed-phase high-performance liquid chromatography. AB - A procedure utilizing reversed-phase high-performance liquid chromatography (HPLC) is described for the identification and quantitation of individual phosphorylated and sulphated fibrinopeptides present in fibrin clot supernatants. Fibrinopeptides from human, rabbit and canine fibrinogens, which have different structures and degrees of phosphorylation and sulphation, were used to demonstrate the applicability of these methods. The procedure relies on the increased peptide hydrophobicity following removal of highly charged phosphate or sulphate groups. Dephosphorylated or desulphated peptides are thus more strongly retained on the reversed-phase HPLC column and are eluted later than their corresponding phosphorylated or sulphated peptide counterparts. Dephosphorylation is achieved by treatment of fibrinopeptide-containing clot supernatants with alkaline phosphatase. Phosphorylated peptides are characterized by an increased retention time resulting from loss of phosphate, whereas non-phosphorylated peptides remain unaffected. Similarly, a prolongation of the peptide retention time resulting from desulphation by mild acid hydrolysis serves to verify sulphation of a peptide. PMID- 3100572 TI - High-performance liquid chromatographic, stability indicating assay for disodium EDTA in ophthalmic preparations. PMID- 3100573 TI - The effect of calcium on the aggregation of chicken gizzard thin filaments. AB - Electron microscopy demonstrates that thin filaments isolated from chicken gizzard smooth muscle in the absence of Ca2+ are aggregated into networks. In contrast, thin filaments isolated in the presence of Ca2+ are dissociated from each other. Electron microscopy also reveals that the respective state of aggregation in each type of preparation is reversible and dependent on Ca2+ concentration. Corresponding viscosity measurements indicate that network formation is associated with an increase in thin filament viscosity. We propose that thin filament aggregation in vivo may be responsible for the tension maintenance of smooth muscle during relaxation. PMID- 3100574 TI - Isolation of multiple normal and functionally defective forms of uridine diphosphate-glucuronosyltransferase from inbred Gunn rats. AB - Gunn rats are a mutant strain of Wistar rats that have unconjugated hyperbilirubinemia due to absence of hepatic uridine diphosphate glucuronosyltransferase (UDPGT; EC. 2.4.1.17) activity toward bilirubin. We isolated five UDPGT isoforms from solubilized microsomal fractions from liver of inbred Wistar (RHA) rats and congeneic Gunn rats. UDPGT isoform V (elution pH 7.5) from Wistar (RHA) rats is active toward bilirubin and 4' hydroxydimethylaminoazobenzene. The corresponding isoform from Gunn rat liver was enzymically inactive but exhibited normal elution pH and mobility on NaDodSO4/polyacrylamide gel electrophoresis (Mr 53,000), and was recognized by a UDPGT-specific antiserum. UDPGT isoform I (elution pH 8.7) from Wistar (RHA) and Gunn rats was active toward 4-nitrophenol. The isoform from Gunn rat liver had only 10% of normal UDPGT activity, however UDPGT activity increased to normal upon addition of 15 mM diethylnitrosamine in vitro. Isoforms II (elution pH 8.4), III (elution pH 8.0), and IV (elution pH 7.8) from Gunn rats had normal UDPGT activities, except that Isoform IV was inactive toward bilirubin. PMID- 3100576 TI - Bone marrow transplantation in canine mucopolysaccharidosis I. Effects within the central nervous system. AB - Five dogs with mucopolysaccharidosis I, a model of human Hurler/Scheie syndrome, were transplanted with marrow from phenotypically normal littermates at 5 mo of age. At 3 and 9 mo posttransplantation, biopsies of cerebral cortex, liver, and cerebrospinal fluid were obtained. The alpha-L-iduronidase levels in these tissues were 0.8-7.4, 26-45, and 6.3-14.9% of the paired donor tissues, respectively. Although iduronidase was present in relatively low levels in the recipients' brains and cerebrospinal fluid at both biopsy times, reduction in brain glycosaminoglycan (GAG) was comparable to that observed in liver. Ultrastructural studies of cells within the transplanted dogs' brains showed less lysosomal distension and storage product than in affected, nontransplanted, littermate controls. The most marked clearing of stored GAG was in cells surrounding blood vessels, but decreased lysosomal storage in neurons and glial cells was also observed. Urinary GAG excretion also decreased to near normal levels by 5 mo posttransplantation. PMID- 3100577 TI - Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I. AB - Recently, we described a patient with severe lactic acidosis due to congenital complex I (NADH-ubiquinone oxidoreductase) deficiency. We now report further enzymatic and immunological characterizations. Both NADH and ferricyanide titrations of complex I activity (measured as NADH-ferricyanide reductase) were distinctly altered in the mitochondria from the patient's tissues. In addition, antisera against complex I immunoprecipitated NADH-ferricyanide reductase from the control but not the patient's mitochondria. However, immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of complex I polypeptides demonstrated that the majority of the 25 polypeptides comprising complex I were present in the affected mitochondria. A more detailed analysis using subunit selective antisera against the main polypeptides of the iron protein fragments of complex I revealed a selective absence of the 75- and 13-kD polypeptides. These findings suggest that the underlying basis for this patient's disease was a congenital deficiency of at least two polypeptides comprising the iron-protein fragment of complex I, which resulted in the inability to correctly assemble a functional enzyme complex. PMID- 3100575 TI - Galactose ingestion increases vascular permeability and collagen solubility in normal male rats. AB - In view of the similarity of cataracts and neuropathy in galactose-fed and diabetic rats, the present experiments were undertaken to determine whether consumption of galactose-enriched diets (10, 25, or 50% by weight) also increases collagen crosslinking and permeation of vessels by 125I-albumin analogous to that observed in diabetic rats. The observations in these experiments: demonstrate that consumption of galactose-enriched diets for 3 wk selectively increases 125I albumin permeation of the same vascular beds affected in diabetic rats and by diabetic vascular disease in humans (i.e., the aorta and vessels in the eye, kidney, sciatic nerve, and new tissue formed in the diabetic milieu); demonstrate that the susceptibility of the vasculature to aldose reductase-linked injury (increased permeability) varies greatly in different tissues; indicate that collagen solubility (crosslinking) changes in galactose-fed rats differ sharply from those in diabetic rats; and provide new evidence that consumption of galactose-enriched diets induces a hypogonadal state in male rats. PMID- 3100578 TI - Apolipoproteins AI, AII, and CI stimulate placental lactogen release from human placental tissue. A novel action of high density lipoprotein apolipoproteins. AB - High density lipoproteins (HDL) stimulated a dose-dependent increase in the release of placental lactogen (hPL) from human placental explants. The stimulation was not prevented by delipidation of HDL but was completely blocked by tryptic digestion. Delipidated apolipoproteins (Apo) AI, AII, and CI also stimulated hPL release but other apolipoproteins were without effect. HDL and Apo CI had no effects on the release of luteinizing hormone and follicle-stimulating hormone from rat pituitary cells or the release of prolactin from human decidual cells. Because placental cells have specific HDL receptors and plasma HDL concentrations increase during pregnancy, these results strongly suggest a role for HDL in the regulation of hPL release during pregnancy possibly independent of their usual role in plasma lipid transport. PMID- 3100579 TI - Quantitative determination of human plasma apolipoprotein A-II by a non competitive enzyme-linked immunosorbent assay. AB - A noncompetitive enzyme-linked immunosorbent assay (ELISA) for apolipoprotein A II (ApoA-II) was developed. Microtiter plates were coated with affinity purified antibodies to ApoA-II. After incubation with human plasma, the amount of ApoA-II bound to the coated plate was determined with peroxidase-labeled antibodies to ApoA-II. When pure ApoA-II or delipidated reference plasma was used as standard, a single step delipidation was required in order to unmask some antigenic sites of ApoA-II. However, the underestimated ApoA-II values in untreated samples were shown to be corrected by using intact reference plasma as secondary standard. The average concentration of ApoA-II in normolipidemic plasma was 0.376 g/l. PMID- 3100580 TI - Cognitive mediation in the affective component of spontaneous panic attacks. AB - Single inhalations of a 50% carbon dioxide/50% oxygen gas mixture were administered to 16 subjects with spontaneous panic attacks and to 16 social phobics who did not experience such attacks. Half of each diagnostic category was randomly allocated to either a no explanation condition in which minimal instructions on expected outcome were provided, or an explanation condition in which all possible sensations were described and attributed to the effects of the gas. Subjects with panic attacks who were given no explanation reported a greater proportion of catastrophic cognitions, greater panic, and a greater similarity of the overall experience to a naturally-occurring panic attack than those with panic attacks who received a full explanation. In contrast, both groups of social phobics reported similar effects to each other, regardless of the explanation given. The results provide support for cognitive mediation in the "panic" component of spontaneous panic attacks. PMID- 3100581 TI - Immunoblot analysis of serological response to Pseudomonas aeruginosa septicaemia in man. AB - The occurrence of an outbreak of Pseudomonas aeruginosa septicaemias on an oncology ward permitted an analysis of antibody responses in patients who were all orally exposed to the same source of infection. Seven patients became septicaemic. Serial serum samples were immunoblotted against the homologous strain. Responses were compared with those of 16 other patients with septicaemias caused by other strains and 10 healthy controls. All 18 survivors produced increasing IgG or IgA antibody, or both, against a 35,000 dalton band, whereas these antibodies were usually absent or fell in titre in the five fatal cases. These antibodies were also lacking in sera taken just before a patient became septicaemic. This band had the electrophoretic characteristics of the outer membrane porin protein F. PMID- 3100582 TI - von Willebrand factor antigen levels in Kaposi's sarcoma. AB - Consistent elevations of plasma von Willebrand factor antigen were observed in otherwise healthy elderly patients with Kaposi's sarcoma. The elevations were predominantly of the endothelial cell--derived antigen, as opposed to the factor VIII procoagulant, with resultant elevations in the antigen/procoagulant ratios. Lesser elevations were seen in a group of age-matched control subjects who did not have Kaposi's sarcoma or intercurrent illness. The greater elevations in plasma von Willebrand factor antigen therefore appear to be the direct consequence of the presence of Kaposi's sarcoma cells. Our findings also suggest that there is a direct relationship between tumor load and degree of von Willebrand factor antigen elevation. PMID- 3100583 TI - Combined total body electron beam irradiation and chemotherapy for mycosis fungoides. AB - Since 1979 a protocol of total body electron beam therapy (3,600 rads; 6 MeV), followed by six monthly cycles of chemotherapy (doxorubicin, 30 mg/M2 given intravenously once monthly, and cyclophosphamide, 100 mg/M2 given orally each day for 14 days), has been used to treat fifty patients with mycosis fungoides (primarily Stages I and II). A group of twenty-four patients, treated by identical high-dose electron beam therapy alone, served as control subjects. Actuarial analysis by the Kaplan-Meier method and statistical analysis by the generalized Wilcoxon test of Gehan demonstrated a significant difference (p = 0.008) in the probability of Stages I and II patients' remaining in complete clinical remission when combination therapy was compared with high-dose electron beam therapy alone. No statistically significant difference was demonstrated in patients in Stages III and IV mycosis fungoides. Although 60% of patients were in "complete clinical remission," the longest follow-up being 75 months, all continued to show karyotypic abnormalities of circulating lymphocytes, and 70% had intermittently and abnormally elevated blood levels of Sezary cells. PMID- 3100584 TI - Electron microscopic and immunolabeling studies of the lesional and normal skin of patients with mycosis fungoides treated by total body electron beam irradiation. AB - Biopsy specimens were taken from lesional and normal skin of nine patients with mycosis fungoides before and after total body electron beam therapy. By electron microscopy, lesional skin had one and one-half to ten times as many epidermal Langerhans cells and indeterminate cells as did the normal skin. In successfully treated lesional skin 1 month after the end of electron beam therapy, the density of epidermal Langerhans cells and indeterminate cells had decreased markedly. In incompletely resolved lesions, Langerhans cells and indeterminate cells were still at pretreatment levels. Epidermal T6 and Ia antigens showed the same pattern of response. Epidermal cell suspensions from lesional and normal skin before and after electron beam therapy were assayed for epidermal thymocyte activating factor. The values of production of this factor did not correlate with the source of the epidermal cells, response to therapy, or the patient's disease course. Skin lesions resembling xerosis and parapsoriasis and histologically lacking the criteria for mycosis fungoides appeared during clinical remissions. These nonspecific skin lesions had densities of epidermal Langerhans cells, indeterminate cells, and T6-positive and Ia-positive cells comparable to levels found in pretreatment lesional skin. PMID- 3100585 TI - Benign lymphoplasia of the earlobes induced by gold earrings: immunohistologic study on the cellular infiltrates. AB - We report three patients with peculiar nodules of the earlobes that developed a few months after the wearing of pierced-type gold earrings. Biopsy specimens showed dense infiltration of lymphoid cells in the dermis and subcutaneous tissue associated with the formation of lymphoid follicles. The clinical and histologic pictures were similar to those of lymphocytoma cutis. Immunohistologically, the nodular lesions were characterized by the proliferation of T cells, mainly suppressor/cytotoxic T cells, and the presence of histiocytic cells displaying Leu-3a antigens on the surface. Patch tests of aqueous gold compound induced a strong skin reaction. A histologic study of the patch test reaction sites revealed a picture of ordinary allergic contact dermatitis showing that T cells, including both helper and suppressor T cells, invaded the spongiotic epidermis and the papillary dermis. Eosinophils and a few Langerhans cells were also present in the dermal infiltrates. These findings suggest that pierced-type gold earrings induced a long-term dermal response that resulted in producing benign lymphoplasia in the sensitized individuals. PMID- 3100586 TI - CT findings of laryngeal involvement in von Recklinghausen disease. AB - In two patients with laryngeal von Recklinghausen disease, CT demonstrated hypodense, well-defined, septated masses sparing the epiglottis, and with little enhancement after contrast medium injection. Additional cervical lesions, benign or occasionally malignant, may also be seen. PMID- 3100587 TI - CT findings in mediastinal extravasation of hyperalimentation fluid. AB - We report a patient with recurrent ovarian carcinoma who developed a mediastinal mass due to extravasated Intralipid hyperalimentation fluid secondary to catheter induced occlusion of the left innominate vein. PMID- 3100588 TI - Influence of milk ultrafiltration on bacteriophages of lactic acid bacteria. AB - Bacteriophages added to whole milk were partially concentrated during ultrafiltration. At 4:1 retentate, phage had concentrated 2.4:1. Thermal destruction at 54 degrees C followed first order kinetics up to 6% protein, whereafter it deviated. When allowed to grow in retentate in the presence of appropriate host, 3.5 generations of phage appeared after 12 h at 22 degrees C compared with four generations in skim milk. In the presence of phage, lactic acid bacteria population increased to only 10(7) cfu/ml compared with 3 X 10(9) in their absence. Retentate starter prepared in the presence of phage was as active as skim milk starter prepared in the presence of phage. PMID- 3100589 TI - A comparison of beta-galactosidase specific activities in strains of Streptococcus thermophilus. AB - Six Streptococcus thermophilus strains were examined for growth, acid production, and beta-galactosidase activity per milligram protein (specific activity), so that strain comparisons could be made. A wide range in activity was observed. Activity depended on growth time in M17 broth and, for most strains, continued to increase after cells had reached stationary phase. Maximum activity was at 16 h and ranged from 0 to 58 units/mg protein. Strain ST exhibited no beta galactosidase activity but had trace phospho-beta-galactosidase activity (.8 units/mg protein after 2 h of growth). Strains 3641 and TS2B exhibited slower growth rates and lower beta-galactosidase activities in milk as compared to M17 broth. Further, strain 3641 exhibited 10 times the activity of strain TS2B (2.86 vs. .24 units) after 4 h of growth in milk. PMID- 3100590 TI - Effect of various conditions on the formation of oligosaccharides in milk treated with beta-galactosidase. AB - Fresh pasteurized milk was inoculated with beta-galactosidase from two different microbial sources at three levels and analyzed for oligosaccharides by high performance liquid chromatography. Five oligosaccharides were observed in the course of hydrolysis. However, only two of these showed measurable increases in concentration. Rate of oligosaccharide formation during hydrolysis was influenced by source and amount of enzymes, reaction time, and temperature. Maximum concentrations of the two oligosaccharides occurred between .5 and 3 d at 7 degrees C and between 1 and 3 d at 1 degrees C, depending on the level of the enzyme used. The higher level of enzyme formed a higher concentration of oligosaccharides than the low level, except at 37 degrees C. After maximum concentration was reached, the two oligosaccharides decreased following hydrolysis, but rate of decrease was dependent upon time, temperature, and enzyme concentration. Hydrolysis of the oligosaccharide was faster at 7 degrees C and at the higher enzyme concentration. Maximum concentration of oligosaccharides was .374 g/100 g milk but was negligible after 7 d, except when the low level of enzyme was used. The total concentration of the oligosaccharides formed in enzyme treated milk was insignificant. PMID- 3100591 TI - Evaluation of dairy and food plant sanitizers against Salmonella typhimurium and Listeria monocytogenes. AB - Six commonly used dairy and food plant sanitizers were evaluated against Salmonella typhimurium and Listeria monocytogenes. Of these six, two were acid anionic sanitizers, one contained a quaternary ammonium compound, one was based on active iodine, and two contained active chlorine. Of the last two, one contained hypochlorite and the other contained active chlorine in organic form. The chlorine-based sanitizers were effective at 100 ppm of available chlorine against both these organisms. The sanitizer containing iodine was effective at 12.5 and 25 ppm titratable iodine against L. monocytogenes and S. typhimurium, respectively. The acid anionic sanitizers were effective at 200 ppm of active agent against both the bacteria, and the quaternary ammonium-based sanitizer was effective at 100 and 200 ppm of active compound against L. monocytogenes and S. typhimurium, respectively. The sanitizer containing iodine at 12.5 and 25 ppm of titratable iodine showed activity equivalent to 50 and 200 ppm of available chlorine, respectively, against L. monocytogenes and 100 and 200 ppm of available chlorine, respectively, against S. typhimurium. PMID- 3100592 TI - Effect of osmolality and glycosaminoglycans on motility, capacitation, acrosome reaction, and in vitro fertilizability of bovine ejaculated sperm. AB - Bovine ejaculated semen was placed in a modified Tyrode's medium with albumin, lactate, and pyruvate. The sperm were washed three times and subjected to nine treatment in a 3 X 3 factorial arrangement. Treatments consisted of osmolality (exposure to 380 mOsmol/kg medium for 5 min, exposure to 340 or 295 mOsmol/kg medium for the entire incubation period), and the presence or absence of glycosaminoglycans (100 micrograms/ml chondroitin sulfate A or 10 micrograms/ml heparin). Sperm were examined at 4.5 h, 8 to 9 h, and 24 to 25 h of incubation (37 degrees C, 5% CO2, and 95% air). Heparin caused head-to-head agglutination of sperm, raised the percent sperm without seminal antigens over the acrosome (capacitated) by 20% at 4.5 h, and doubled the percent of acrosome-reacted sperm. However, this stimulation did not improve in vitro fertilizability. Chondroitin sulfate A tended to maintain motility, but did not affect capacitation or the acrosome reaction, possibly due to glucose inhibition. Both high osmolality treatments tended to reduce motility, especially after 24 h of incubation when the 340 osmolality treatment reduced motility by 14% over the 295 treatment. No consistent effect on capacitation was observed. The 340 and 380 osmolality treatments induced 8.6 and 6.1% more acrosome reactions by 24 h than the 295 treatment. The 340 mOsmol/kg treatment yielded insignificantly higher in vitro fertilization rates, as evidenced by development of zygotes to the two-cell stage. Lack of statistical significance was due to high variation with in vitro fertilization rates. PMID- 3100594 TI - Cost effectiveness of prevaccination screening for hepatitis B antibody. AB - The cost effectiveness of screening for hepatitis B antibodies prior to instituting a vaccination program was investigated. Prevaccination screening tests for anti-HBs were performed on sera from 295 faculty and staff. Anti-HBs positive titers were found for 58 persons, and 43 (14.6 percent) of these had titers high enough to confer immunity. The cost of screening 295 persons was $1,666.64, or $5.65 per participant. By not vaccinating 43 persons, $4,498.23 was saved. A prevaccination screening would be most cost effective if only faculty with patient contact were screened. PMID- 3100593 TI - Dimensional stability of alginate impressions immersed in disinfecting solutions. AB - The stability of full-arch alginate impressions that had been immersed in one of two disinfecting solutions was assessed by measuring stone casts poured from the alginate impressions. Statistically significant dimensional changes occurred, when compared with master casts, but only by 1 mm or less, a clinically insignificant amount. PMID- 3100595 TI - CO2 laser treatment of cutaneous neurofibromas. AB - Cutaneous benign neurofibromas are the most common skin manifestation of Von Recklinghausen neurofibromatosis (NF). An autosomal dominant disorder, NF has extraordinary clinical variability and multisystem involvement; many patients develop hundreds of cutaneous neurofibromas in a lifetime. This problem can easily and rapidly be treated using the CO2 laser with results equal to or better than excision. The procedure is very helpful for patients with large numbers of small- or medium-sized cutaneous neurofibromas. PMID- 3100596 TI - Pouching and refeeding system for infant with dual bilateral ostomies. PMID- 3100597 TI - Multiple linear ulcers on the dorsum of the tongue in a patient with Waldenstrom's macroglobulinemia. AB - An unusual clinical presentation of an eosinophilic ulcer of the tongue has been described. This lesion is seen most often in the fourth to sixth decades of life and has been shown to have a strong predilection for males. The etiology is unknown although trauma has been implicated by several investigators. Because of the clinical resemblance of eosinophilic ulcer to carcinoma, biopsy examination is recommended. After the diagnosis is made, conservative management is most appropriate. PMID- 3100598 TI - Plasma tissue plasminogen activator inhibitor levels in coronary artery disease: correlation with age and serum triglyceride concentrations. AB - Increased levels of an endogenous inhibitor of tissue-plasminogen activator (t PA) have been thought to relate to the genesis of acute myocardial ischemia. To examine the role of the rapid inhibitor of t-PA, plasma samples were analyzed from 75 patients with chest pain syndrome undergoing coronary angiography (mean age 57 years), 24 patients with clinically documented coronary artery disease (unstable angina, positive exercise stress test or previous history of myocardial infarction; mean age 58 years) and 15 young normal subjects (mean age 26 years). Plasma t-PA inhibitor levels were similar in age-matched patients regardless of the absence or presence (and degree) of coronary artery disease. Plasma t-PA inhibitor levels correlated significantly with age (r - 0.46, p less than 0.005), suggesting an age-dependent decrease in fibrinolytic activity. Plasma t-PA inhibitor levels also correlated significantly with serum triglyceride levels (r 0.60, p less than 0.001), but not with coronary risk factors such as serum cholesterol, diabetes, hypertension, serum uric acid levels or body weight. Association of high levels of inhibitor of t-PA with hypertriglyceridemia may be of importance in the development of coronary thrombosis, especially in elderly patients. Nonetheless, this study does not suggest a pathogenic role of t-PA inhibitor in coronary atherosclerosis. PMID- 3100599 TI - Effect of flecainide acetate on prevention of electrical induction of ventricular tachycardia and occurrence of ischemic ventricular fibrillation during the early postmyocardial infarction period: evaluation in a conscious canine model of sudden death. AB - The antiarrhythmic and antifibrillatory effects of flecainide acetate during the early postinfarction period were evaluated in a conscious canine model of sudden cardiac death. Ventricular tachycardia remained inducible early after infarction in eight of nine dogs receiving an intravenous loading dose of flecainide (2.0 mg/kg body weight) and seven of eight dogs receiving saline vehicle. In both the drug and vehicle groups, there was no significant change in the ventricular refractory period or in the cycle length of the induced ventricular tachycardia. With a maintenance intravenous infusion of flecainide, 1.0 mg/kg per h for 4 hours, the subsequent occurrence of acute posterolateral ischemia resulted in the development of ventricular fibrillation and sudden death in seven of eight flecainide-treated and eight of eight vehicle-treated dogs. Seven additional postinfarction dogs with noninducible tachycardia during pretreatment programmed stimulation, and thereby considered to be at "low risk" for the development of ischemic ventricular fibrillation, were also given flecainide in an intravenous loading and maintenance dosing regimen. The subsequent occurrence of posterolateral ischemia resulted in the development of ventricular fibrillation in three of these seven dogs. These findings suggest that flecainide acetate may not possess pharmacologic properties useful in managing ventricular tachycardia or in preventing ischemic ventricular fibrillation in the presence of recent myocardial damage. PMID- 3100600 TI - Pharmacokinetic-hemodynamic studies of transdermal nitroglycerin in congestive heart failure. AB - Ten patients with chronic congestive heart failure were studied to assess the hemodynamic effects and bioavailability of a transdermal nitroglycerin delivery system. Nitrate sensitivity was defined by a prior 20 minute infusion of nitroglycerin, 21 micrograms/min. Five patients with a satisfactory hemodynamic response to intravenous nitroglycerin received two nitroglycerin patches of 10 cm2 each and five patients who did not achieve a satisfactory response to intravenous nitroglycerin (that is, greater than or equal to 25% reduction in left ventricular filling pressure) received larger doses of transdermal nitroglycerin. In the five nitrate-sensitive patients who received 20 cm2 of transdermal nitroglycerin, one study was terminated at 90 minutes, at which point there was no detectable hemodynamic response or arterial plasma nitroglycerin evident. Two patients had a minimal hemodynamic response and a peak plasma concentration of 1 ng/ml. A fourth patient had a short-lived hemodynamic response at 60 and 120 minutes and a plasma nitroglycerin concentration of 1 ng/ml at 60 minutes. A fifth patient had a hemodynamic response persisting for 24 hours and plasma concentrations between 0.6 and 1.1 ng/ml. The remaining five patients showed little or no hemodynamic response despite doses of transdermal nitroglycerin from 40 to 60 cm2. The highest plasma concentration achieved in these patients was 2 ng/ml and there was no relation between dose administered and plasma concentration achieved. In 4 of the 10 patients who subsequently received nitroglycerin ointment, there were a greater decrease in left- and right sided filling pressures and greater increase in plasma nitroglycerin concentrations (from 1.6 to 4.8 ng/ml) than those that occurred with transdermal nitroglycerin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100602 TI - Announcement of protocol change in thrombolysis in myocardial infarction trial. PMID- 3100601 TI - Second generation antiarrhythmic agents: have we reached antiarrhythmic Nirvana? PMID- 3100603 TI - Genentech experience with rt-PA (activase) PMID- 3100604 TI - Taking the next step: clinical research in the long-term care facility. PMID- 3100605 TI - Lithium-verapamil toxicity in the elderly. PMID- 3100606 TI - Platelet population profiles: significance of species variation and drug-induced changes. AB - Platelet counts are routinely assessed from whole blood samples and recent technical advances enable the total platelet counts to be complemented by additional information which fully profiles the platelet population. In this report the platelet count, mode and mean platelet volumes and platelet profile histograms are presented for eight mammalian species. Species and strain variation in platelet profiles and the degree of volume heterogeneity are presented, and a platelet profile is presented for the marmoset which is previously unreported. The significance of these parameters and their potential importance to the toxicologist are discussed in the light of an observation of a drug-induced alteration in a platelet population profile. PMID- 3100607 TI - [Alleviation of ocular complications of the hyperviscosity syndrome in Waldenstrom's macroglobulinemia using plasma exchange]. AB - Two patients presenting ocular complications of hyperviscosity syndrome in Waldenstrom's macroglobulinemia have been treated by plasmapheresis after inefficiency of immunosuppressive therapy. Plasma exchange seems an useful treatment as shown by clinic and angiographic improvement. In each case improvement of retinopathy was correlated with decrease of serum IgM level and blood viscosity measured by isotopic method. Fluorescein angiography, easily repeated, seems a very good method for following hyperviscosity syndrome in Waldenstrom's macroglobulinemia. PMID- 3100608 TI - [Synthetic absorbable PDS explant for the treatment of retinal detachment]. AB - The following article discusses the experimental and clinical reasons for using absorbable synthetic explants in retinal surgery. We have carried out experimental studies with absorbable synthetic explants bandmade from absorbable sewing threads: PG910, PGA and PDS; proving that these explants are well tolerated by the organism. Their reabsorption time is from 45 days using PG910, to 8 months using PDS; these periods are sufficient for proper anatomical healing of the retina to take place. We present 13 cases of extraction of Teflon explants after retinal detachment surgery; in none of these cases did re-detachment of the retina occur. Consequently, this induced us to introduce absorbable synthetic explants into retinal detachment surgery, using absorbable threads, having previously carried out an experimental study on rabbits. We present 10 cases of retinal detachment operated on with PDS from 95 cases operated on using absorbable synthetic explants; 100% anatomical healing of the retina was achieved. We consider this type of explant to be the ideal material for retinal detachment healing, due to the fact that its period reabsorption, being longer than those of the other explants, allows a longer indentation period. PMID- 3100609 TI - Recurrent upper gastrointestinal bleeding from a cavernous hemangioma in a duodenal diverticulum. PMID- 3100610 TI - A clinicoparasitological study of scabies. PMID- 3100611 TI - Comparison of direct-microscopy, culture and latex agglutination tests for the diagnosis of meningococcal meningitis. PMID- 3100612 TI - Ceftazidime, a broad spectrum cephalosporin with activity against Ps. aeruginosa. AB - Ceftazidime is one of the oximinoaminothiazolyl cephalosporins with resistance to most B-lactamases from gram-negative bacteria, and a very wide spectrum of activity including Ps. aeruginosa. MIC's of less than 0.1 mg/l are seen routinely against E. coli, K. pneumoniae, E. cloacae, Proteus spp. both indole positive and negative, Serratia sp., and Providence sp. The mean MIC against clinical isolates of Ps. aeruginosa is less than 2 mg/l. It is bactericidal at concentrations close to the MIC and its activity is unimpaired in the presence of serum. Ceftazidime is well distributed in the body, penetrating into all body fluids at concentrations excess of the MIC's of most pathogenic bacteria. It has a half life of about 1.5 hours, is excreted almost exclusively by the kidney and is not bound to serum proteins. More than 12,000 patients have now been treated with the antibiotic, with an overall success rate of more than 93%. PMID- 3100613 TI - Lymphotoxin: induction of terminal differentiation of the human myeloid leukemia cell lines HL-60 and THP-1. PMID- 3100614 TI - Growth inhibition of human T cells by antibodies recognizing the T cell antigen receptor complex. AB - Monoclonal antibodies that bind to the T cell MHC-antigen recognition complex (anti-T3 or anti-Ti) are known to either mimic ligand binding and activate T cells or block ligand binding, leading to an inhibition of T cell activation. In the present experiments, we demonstrate a direct inhibitory effect on the growth of human T cells by anti-T3 or anti-Ti antibodies. The proliferation of human peripheral blood T cells preactivated by exposure to PHA was inhibited in a specific manner by anti-T3. Colony formation in soft agar by REX cells, a leukemic cell line of early T cell phenotype, was completely inhibited by anti-T3 or anti-Ti antibodies, whereas isotype-matched antibodies to a variety of other T cell markers had no effect. Growth of REX cells in suspension culture was not affected by anti-T3 or anti-Ti. A cell line, T3.N1, was established from an agar colony of anti-T3-resistant REX cells. T3.N1 was phenotypically identical to REX except for failure to express any detectable T3 or Ti surface antigen. T3.N1 colony formation in soft agar was not inhibited by anti-T3 or anti-Ti. There was no rise in [Ca2+]i of T3.N1 cells after anti-T3 or anti-Ti exposure. These results indicate that in addition to the well-known positive regulatory effects of ligand binding to the T3/Ti complex, T3/Ti binding can also result in a down regulatory signal for human T cell growth. PMID- 3100615 TI - Immune interferon enhances functional properties of human granulocytes: role of Fc receptors and effect of lymphotoxin, tumor necrosis factor, and granulocyte macrophage colony-stimulating factor. AB - We report here a comparative study of the effects of several cytokines known to affect myeloid cell differentiation on functional properties of human mature granulocytes. We show that recombinant interferon-gamma (rIFN-gamma), recombinant granulocyte/macrophage-colony stimulating factor (rGM-CSF), recombinant tumor necrosis factor (rTNF), and lymphotoxin (LT) purified to homogeneity are potent stimulators of polymorphonuclear cells (PMN) activity. All cytokines enhance antibody-dependent cell-mediated cytotoxicity (Ab-CMC) mediated by human PMN; however, rGM-CSF, rTNF, and LT have an immediate and short-lived effect on the PMN, whereas the activation by rIFN-gamma requires several hours of induction but can be observed up to 24 to 48 hr of culture. Only the effect of rIFN-gamma is in part dependent on induction of a high-affinity FcR for monomeric IgG on PMN, as suggested by two-color sorting analysis, and on mechanisms that result in prolonged survival of PMN in a functionally active state to mediate oxidative burst, phagocytosis, and bactericidal activity. Greater enhancement of Ab-CMC is obtained by using rIFN-gamma in combination with the other cytokines. Our data indicate that cytokines previously defined on the basis of their cytotoxic effects mediate a wide spectrum of activities on mature myeloid cells and provide evidence for their possible role in vivo, alone or in combination with rIFN gamma, in modulating functional activities of cells responsible for non-adaptive systems of defense. PMID- 3100616 TI - The role of interleukin 2 in inducing Ig production in a pokeweed mitogen stimulated mononuclear cell system. AB - Cyclosporin A (CsA) has been found previously to block mitogen-stimulated T cell proliferation and production of discrete T cell-derived lymphokines such as interleukin 2 (IL 2) and interferon (IFN)-gamma. In addition, CsA blocks pokeweed mitogen (PWM)-driven T cell-dependent differentiation of B cells into immunoglobulin (Ig)-secreting cells. Recently, we reported that CsA (1 microgram/ml) inhibited PWM-induced T cell production of IL 2 and IFN-gamma, but supernatants retained B cell differentiation factor (BCDF)-like activity. The present study demonstrates the ability of CsA to suppress T cell functions in PWM driven Ig production in mononuclear cells (MNC), and the capacity of exogenous T cell lymphokines to reverse CsA-induced suppression. CsA profoundly suppressed PWM-driven PFC formation (greater than 95%). However, Ig production was substantially reconstituted by the addition of IL 2 at concentrations of 10 to 50 U/ml. In contrast, no effects were observed by the addition of IFN-gamma or BCGF. The kinetics of CsA inhibition of Ig production and IL 2 secretion were found to be closely related. In addition, to obtain effective reconstitution in the CsA treated PWM-MNC system it was necessary to add IL 2 at the initiation of culture. T cells themselves were also required for B cell differentiation in this system. However, surface Ig+ cells obtained by cell sorting after 3 days of culture could differentiate in the absence of T cells but only in response to IL 2, not in response to IFN-gamma or BCDF. Thus, in PWM-driven B cell differentiation T cells are necessary early in culture, whereas IL 2 is essential from the initial stage of B cell activation through the final stage of B cell differentiation. PMID- 3100617 TI - Expression of the human T cell receptor as defined by anti-isotypic antibodies. AB - Anti-isotypic reagents against the human T cell receptor (TcR) were made by immunizing rabbits with peptides which corresponded to sites within the constant region of the alpha- and beta-chains. These antibodies were shown to immunoprecipitate a heterodimer of 80,000 to 90,000 m.w. that could be reduced to chains of 44,000 to 50,000 and 37,000 to 40,000 m.w. In addition, an anti-peptide serum against CD3 delta-chain was made. The anti-alpha peptide serum reacted with all human TcR (from phytohemagglutinin-stimulated lymphocytes, cytotoxic T cell clones, and the T cell leukemias: HPB-ALL, Jurkat, JA3, and JM), and the anti beta peptide serum reacted with only human TcR of the C beta 2 isotype (from a cytotoxic T cell clone which had a C beta 2 transcript, HPB-ALL, and a proportion of phytohemagglutinin-stimulated lymphocytes, but not with Jurkat, JA3, and JM). A comparison of the detergents NP-40 and digitonin revealed that digitonin was more efficient at keeping the TcR/CD3 complex intact, but was less efficient at solubilizing the total amount of TcR or the total amount of CD3. With these reagents and the use of digitonin, it was shown that all of the alpha, beta, and CD3 moieties on the surface of a T cell leukemia HPB-ALL occur as a bound TcR/CD3 complex. The proportion of C beta 1 to C beta 2 isotype expressed on the surface of phytohemagglutinin-stimulated peripheral blood lymphocytes was 0.8, indicating approximately equal use of the two beta-chain isotypes. PMID- 3100618 TI - Multimeric C9 within C5b-9 is required for inner membrane damage to Escherichia coli J5 during complement killing. AB - We have shown recently that an average of three or more C9 molecules must bind to C5b-8 on Escherichia coli strain J5 to cause direct complement killing in the absence of serum lysozyme. We initially confirmed and extended this observation by showing that deposition of a large number of C5b-9 complexes bearing 1C9 per C5b-8 was not bactericidal for J5. To identify the target site for bactericidal C5b-9 deposition, we measured release of periplasmic and cytoplasmic markers of different size from J5 as the C9:C5b-8 ratio was changed, because the diameter of the C5b-9 channel is known to increase as the C9:C5b-8 ratio increases. To facilitate measurement of release of the periplasmic marker beta-lactamase (BLA), J5 was transformed for high level constitutive TEM-1 BLA production (J5-Amp). Multimeric C9 within C5b-9 (C9:C5b-8 greater than 3) was required to release BLA (m.w. 28,900) from J5-Amp regardless of whether cells bore 310, 560, or 890 C5b 9/organism. Curves of both BLA release and killing vs C9:C5b-8 ratio were sigmoidal and nearly superimposable. Release of the small cytoplasmic marker 86Rb, a potassium analog, also required a minimum C9:C5b-8 ratio of 3:1; specific 86Rb release did not occur in the absence of killing. Release of the large cytoplasmic marker beta-galactosidase (m.w. 505,000) did not occur even at the highest achievable C9:C5b-8 ratio of 11:1, despite greater than 99.9% killing, indicating that there was no dissolution of the peptidoglycan layer due to incomplete removal of serum lysozyme. Complement-mediated killing of J5 requires sufficient damage to the outer membrane or formation of a sufficiently large C5b 9 channel to release the large periplasmic marker BLA. The requirement of multimeric C9 for 86Rb release suggests that at low C9:C5b-8 ratios, either C5b-9 does not have access to the cytoplasmic space or that the J5 K+ transport systems are able to compensate for putative C5b-9 channels. PMID- 3100619 TI - Experimental cutaneous leishmaniasis. II. A possible role for prostaglandins in exacerbation of disease in Leishmania major-infected BALB/c mice. AB - Leishmania major infection in genetically susceptible BALB/c mice is associated with the development of chronic primary lesions as well as multiple metastatic lesions. Spleen cells from these mice were shown to have depressed in vitro responses to concanavalin A (Con A) that coincided with the development of indomethacin-sensitive suppressor cells. Depressed responses to Con A were noted as early as 1 wk after parasite inoculation and correlated with the increased production of prostaglandin E2 (PGE2) by spleen cells from infected mice. Mice induced by prior irradiation (550 rad) to heal infection did not develop indomethacin-reversible depression in responsiveness to Con A. Although macrophages appear to be the major source of PGE2 production, in vitro studies indicate that infection per se is not a sufficient stimulus to initiate prostaglandin (PG) synthesis, suggesting the involvement of other cell types. Mice treated in vivo with indomethacin exhibited significantly fewer metastatic lesions than control mice, suggesting that PG may play a role in the exacerbation of cutaneous disease in these animals. PMID- 3100620 TI - An analysis of T cell responsiveness in Indian kala-azar. AB - The inability of most untreated patients with Kala-azar to control their visceral infections with Leishmania donovani has been attributed to a defective cell mediated immune response to leishmanial antigens. We examined the in vitro response of T cells, including Leu-2+-depleted T cell populations, to determine whether unresponsiveness could be reversed. These studies on patients with visceral leishmaniasis in Bihar, north India, support previous observations regarding T cell unresponsiveness in patients with active disease: it is profound, it is specific, and it is reversible after successful chemotherapy. However, these studies also indicate that the specific unresponsiveness cannot be reversed by depletion of "suppressor" Leu-2+ T lymphocytes, nor by the addition of exogenously supplied human IL 2 to the cultures. One interpretation of these results is that in active cases of Kala-azar, there is an absence of Leishmania specific T cells in the periphery. The possibility that reactive cells can be found in situ cannot be excluded. The observation that 13 of 25 family members of active cases were able respond to L. donovani in vitro or by skin testing suggests that the frequency of infection within an endemic area in Bihar is very high, and that assays for T cell responsiveness are far better epidemiologic tools for the detection of asymptomatic infection than is ELISA. Identification of such an exposed, Kala-azar-resistant population will be required to study host factors which influence the development of disease in infected individuals. PMID- 3100621 TI - Two V kappa germ-line genes related to the GAT idiotypic network (Ab1 and Ab3/Ab1') account for the major subfamilies of the mouse V kappa-1 variability subgroup. AB - V kappa Ig germ-line genes have been isolated from recombinant clones prepared in separate libraries constructed from adult BALB/c liver DNA. Three different clones that strongly hybridized with a V kappa-GAT-specific probe were completely characterized and sequenced. All three genes exhibited common characteristic features in their sequences encompassing the 5' to the 3' noncoding region, with coding sections 95% homologous. A comparison with other V kappa genes shows that the size of the first intron is variability subgroup specific. Moreover, a direct correlation exists between the size of this intron and the entire length of the coding region. Nucleotide sequences of these genes were compared with V kappa chains expressed at the Ab1 and Ab1' levels of the GAT idiotypic network: Ag--- Ab1----Ab2----Ab3 (Ab1'). K1A5 and K5.1 genes account for V kappa chains in Ab1 and Ab1' hybridomas, respectively. The high conservation of Ab1' sequences in light chain was also recently reported for the heavy chains, suggesting that immunization with Ab2 (anti-idiotypic) antibodies preferentially stimulates the direct expression of germ-line genes. K5.1 and K1A5 genes belong to the V kappa-1 variability subgroup and encode, without any amino acid substitution, V kappa domain in myeloma TEPC 105 and MOPC 467, which are V kappa-1A and V kappa-1C subgroup prototypes, respectively. These genes are extensively used in different mouse strains and in a number of antibodies of discrete specificities, such as anti-GAT, anti-DNP, anti-flagellin, anti-phosphorylcholine, anti-digoxin, anti phenyloxazolone, and anti-DNA. PMID- 3100622 TI - Lipopolysaccharide-mediated macrophage activation: the role of calcium in the generation of tumoricidal activity. AB - As we have reported, calcium ionophore A23187 activates macrophages for tumor cell killing, and the activated macrophages produced a soluble cytotoxic factor (M phi-CF) that is similar, if not identical, to tumor necrosis factor. Based on these observations, we have investigated whether calcium is involved in the activation mediated by another potent macrophage activator, namely lipopolysaccharide (LPS). We first showed that A23187 caused uptake of extracellular calcium-45 by macrophage monolayers, whereas LPS did not. Because in this system rapid changes would not have been detected, several other approaches also have been used. We have examined the effect of depleting extracellular calcium by using medium containing no added calcium, supplemented with 1 mM EGTA. In no case did depletion result in decreased M phi-CF production by LPS-treated macrophages. Measurements using the fluorescent intracellular calcium indicator Quin 2 have also been performed. The calcium ionophore ionomycin caused a rapid change in the intracellular Quin 2 signal. LPS, even at a concentration in vast excess of that required to activate the macrophages, caused no change in the signal during a 2-hr period. If the macrophages were loaded with high doses of Quin 2 or another intracellular chelator, TMB-8, M phi CF production decreased and cytotoxic activity was impaired. These data indicate that one or more of the processes involved in M phi-CF production does require calcium, but that activation mediated by LPS occurs without the influx of extracellular calcium or redistribution of intracellular calcium. PMID- 3100623 TI - Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. AB - Tumor-infiltrating lymphocytes from six patients with metastatic malignant melanoma were expanded by culture in recombinant interleukin 2. Three of the preparations were highly cytotoxic against autologous fresh melanoma tumor cells, but not against autologous fresh normal cells or allogeneic fresh tumor targets. The other three were highly cytotoxic against autologous fresh melanoma tumor cells and also had a limited capacity to kill allogeneic fresh tumor targets. The tumor-associated specific killer cells could be expanded from threefold to 95,652 fold with maintenance of specific antitumor lysis. The expanded tumor infiltrating cells were Leu-4+ T cells, and in five of six patients the majority were Leu-3+. These studies demonstrate that the melanoma-bearing patient raises an immune response against autologous tumor and presents a method for the generation of human lymphocytes with antitumor reactivity that may be useful in the adoptive immunotherapy of tumors. PMID- 3100624 TI - Phenotypic identification of memory cytolytic T lymphocytes in a subset of Lyt-2+ cells. AB - Murine peripheral Lyt-2+ T cells could be subdivided according to surface expression of the Pgp-1 glycoprotein into major (71%) Pgp-1- and minor (29%) Pgp 1+ subsets. A striking correlation was observed between Pgp-1 expression and enrichment for antigen-specific memory cytolytic T lymphocyte precursors (CTLp). After immunization with the male minor transplantation antigen H-Y, virtually all the H-Y-specific CTLp were found in the minor Pgp-1+ subset of Lyt-2+ cells. In addition, after alloimmunization the frequency of allospecific CTLp resistant to inhibition by anti-Lyt-2 antibody was markedly enriched within the Pgp-1+ cells, suggesting an enrichment for CTLp bearing high avidity antigen receptors. Taken together, these data suggest that surface Pgp-1 expression is stably acquired at the time of primary antigenic stimulation by virgin T cells. As such, Pgp-1 represents an important marker for identifying a subset of Lyt-2+ T cells with the quantitative and qualitative properties of memory CTLp. PMID- 3100625 TI - Target cell recognition structures in LDCC and ODCC. AB - Cytotoxic T lymphocyte effector cells specific for a defined class I antigen can kill target cells displaying a wide range of different class I proteins in the presence of certain lectins and oxidizing agents. However, optimal lysis of the target cell (TC) still requires interaction of the CTL with the TC class I proteins. This raises the question of how the lectin or oxidizing agent alters the system in such a way that an "inappropriate" CTL-TC interaction takes place, in a class I-dependent manner. In this study we show that if papain-sensitive molecules are cleared from the TC surface and are allowed to regenerate in the presence of tunicamycin, the cells still serve as targets in direct, class I antigen-specific CTL killing, but not in LDCC or ODCC. Target cells treated in this way display N-linked carbohydrate-less class I proteins, and presumably other N-linked carbohydrate-less, papain-sensitive molecules as well. We present data showing that both types of molecules are important in nonspecific lytic reactions. PMID- 3100626 TI - The B cell is the initiating antigen-presenting cell in peripheral lymph nodes. AB - We have examined the role of B cells in antigen presentation in lymph nodes in several ways. We found that mice depleted of B lymphocytes via chronic injection of anti-mu-chain antibody do not mount peripheral lymph node T cell proliferative responses to normally immunogenic doses of antigen. Depletion of B cells by passage of immune lymph node cells over anti-immunoglobulin columns early after immunization depletes antigen-presenting function from draining lymph nodes, and this function can be restored by using B cells or splenic adherent cells to allow the remaining T cells to proliferate. Lymph node B cells present antigen very effectively to lines of antigen-specific T cells. However, unfractionated lymph node cells from anti-mu-treated mice present very poorly, if at all, whereas unfractionated spleen cells from the same mice do present antigen. This is in keeping with our previous finding that helper T cell function in the spleen is normal in B cell-deprived mice. Finally, when mice homozygous for the lymphoproliferative gene lpr are treated chronically with anti-mu-chain antibody, lymphadenopathy is greatly retarded, suggesting a role for B cells in the massive proliferation of T cells in this syndrome. From this analysis, it would appear that the initiating antigen-presenting cell in the lymph node is a B lymphocyte, and that B lymphocytes in lymph nodes may be distinct from those in the spleen. It is of interest that these results also suggest that the lymph node lacks an antigen-presenting cell that is found in the spleen, perhaps the dendritic cell. PMID- 3100627 TI - Human lymphokine-activated killer (LAK) cells: identification of two types of effector cells. AB - We analyzed the antigenic phenotype of lymphokine-activated killer (LAK) effector cells. Human blood lymphocytes were cultured for 3 days with 100 U/ml recombinant interleukin 2 (rIL 2), subpopulations isolated with monoclonal antibodies and a fluorescence-activated cell sorter (FACS) and assayed for cytotoxic activity against 51chromium labeled noncultured melanoma tumor cells. Initial experiments compared the LAK effector function of CD5+ T lymphocytes vs CD5- cells (predominantly CD16+ NK cells). The mean percent specific release at a 10:1 effector:target (E:T) ratio was 25% +/- 16 for CD5- cells, 10% +/- 6 for CD5+ cells, and 22% +/- 9 for unsorted cells. In contrast, when lymphocyte subpopulations were isolated before rIL 2 culture (LAK precursors), CD5- cells but not CD5+ cells developed LAK activity (28% +/- 12 vs 1% +/- 1, mean percent specific release, 10:1 E:T ratio), confirming our previous results showing that only CD16+ cells were LAK precursors. The discrepancy between LAK effector and precursor phenotypes suggested that LAK precursors acquired CD5 determinants during rIL 2 culture; however, double label immunofluorescence of rIL 2 cultured CD16+ cells showed that this was not the case. The data suggested that in the presence of other cell types, some T lymphocytes may develop LAK activity, but purified blood T lymphocytes do not develop LAK function when cultured with rIL 2 alone. We also analyzed LAK effector function in lymphocyte subpopulations defined by CD4 and CD8 antigens. The data showed that lymphocytes with a low density expression of CD8 and no expression of CD4 were enriched for LAK effector cells, whereas CD4+ and CD8- had less activity than unsorted cells. Lymphocytes with a high density expression of CD8 had activity similar to unsorted cells. We also assessed the contribution of Leu-7 (HNK-1) granular lymphocytes to LAK effector function. After culture with IL 2, lymphocytes were depleted of Leu-7+ cells by antibody and complement treatment and then were sorted into CD5+ and CD5 fractions. The cytotoxic activity of Leu-7-CD5+ cells was a mean 5% +/- 5 vs a mean 14% +/- 8 for the total CD5+ population (20:1 E:T ratio). The activity of Leu-7- CD5- was slightly less than the total CD5- fraction (21% +/- 9 vs 28% +/- 14, 10:1 E:T ratio). In conclusion, LAK effector function was highest in non-T cell (CD5- CD16+) populations and some activity was also present in T cell populations (CD5+ and predominantly Leu-7+). PMID- 3100628 TI - Arsonate-specific murine T cell clones. IV. Properties of I-E- and I-A-restricted clones. AB - The T cell antigen L-tyrosine-p-azobenzenearsonate is unique in being a simple determinant that can be presented in the context of both I-A and I-E. I-E restricted T cell clones derived from B10.A(5R) mice were found to fall into three groups: Type I clones recognized antigen only in the context of syngeneic apcs, Type II clones recognized antigen with the same highly specific major histocompatibility complex restriction but in addition proliferated in response to allogeneic stimuli; Type III clones were "degenerate" in their major histocompatibility complex-restricted recognition of antigen and proliferated when antigen-presenting cells bearing Eb beta Ek alpha (syngeneic), Ek beta Ek alpha, or Ed beta Ed alpha were used. These observations allow some conclusions to be drawn about sites on the I-E molecule that may be functionally significant in the presentation of this antigen. By using the B cell hybridoma LK35.2 as target cells, some of these T cell clones act as cytotoxic cells in the Class II restricted manner predicted from the results of proliferative assays. Class II restricted cytotoxicity can therefore be controlled by both I-A and I-E mouse Ir gene loci. PMID- 3100629 TI - Anti-T cell receptor antibodies fail to inhibit specific lysis by CTL clones but activate lytic activity for irrelevant targets. AB - In this report, we describe the functional effects of anti-T cell receptor antibodies on a panel of MHC-restricted, influenza virus-specific CTL clones. Approximately 25 to 30% of these clones are recognized by KJ16-133, an anti-T cell receptor monoclonal antibody presumably specific for products of the V beta 8 gene family, and an antibody with similar specificity, F23.1. In contrast to most previous reports, both KJ16-133 and F23.1, over a wide range of antibody concentrations, fail to inhibit the antigen-specific effector function of these CTL. Instead, the antibodies activate the CTL to kill without regard for the MHC haplotype of the target cells or the presence of the appropriate viral antigen. This anti-T cell receptor antibody-induced cytolysis by our clones does not appear to be mediated by Fc receptors on target cells. Nuclear destruction of target cells as a result of antibody-induced lysis suggests that it occurs via a mechanism similar to antigen-specific lysis by CTL. In addition, both soluble bivalent F23.1 and F23.1 coupled-Sepharose beads are able to induce the secretion of interferon-gamma from these CTL clones. PMID- 3100630 TI - Macrophage activation for antileishmanial defense by an apparently novel mechanism. AB - Activation of macrophages by lymphokines (including interferon-gamma; IFN-gamma) is presently considered to be a major host defense mechanism against a number of intracellular microorganisms. In a series of earlier studies that made use of mice undergoing spontaneous resolution of footpad infections with Leishmania major, we obtained evidence suggesting that a subpopulation of Leishmania sensitized lymph node T lymphocytes could activate antimicrobial effects in Leishmania-infected macrophages by an apparently lymphokine-independent mechanism. These effector lymphocytes are not cytotoxic to host cells, and their effects are antigen specific and genetically restricted. To more rigorously investigate this apparently novel mechanism of macrophage activation, we examined the effect of blocking lymphokine production with cyclosporin A (CSA) on the capacity of these effector lymphocytes to exert macrophage activating function. Although CSA blocked lymphokines that activate antileishmanial effects, it did not inhibit the antimicrobial capacity of the effector lymphocytes. We also confirmed that IFN-gamma is the major macrophage-activating lymphokine that induces antileishmanial effects; treatment of lymphokine-containing supernatants with anti-IFN-gamma antibody markedly reduced their antimicrobial effects. In contrast, treatment of effector lymphocytes with this antibody failed to reduce their macrophage-activating capacity. We conclude that there exists an apparently novel macrophage-activating mechanism for antimicrobial defense that is independent of soluble lymphokine mediators. PMID- 3100631 TI - T cell receptor-CD3 complex during early T cell differentiation. Analysis of immature T cell acute lymphoblastic leukemias (T-ALL) at DNA, RNA, and cell membrane level. AB - T cell acute lymphoblastic leukemias (T-ALL) can be regarded as the malignant counterparts of cells in various T cell differentiation stages. To study the expression of the human T cell receptor (TcR)-CD3 complex during the early stages of T cell differentiation, we have analyzed 22 T-ALL at the cell membrane level and the DNA level and 12 of them at the RNA level. According to their immunologic phenotype, the T-ALL could be divided into three main groups: 10 immature T-ALL (CD1-/CD3-), seven common thymocytic T-ALL (CD1+/CD3-or+), and five mature T-ALL (CD1-/CD3+). Among the 10 immature T-ALL three appeared to express the immunologic phenotype of the putative prothymocyte (TdT+/HLA-DR+/CD7+/CD2+/CD5 /CD1-/CD3-), whereas the other seven T-ALL appeared to be immature thymocytic (TdT+/HLA-DR-/CD7+/CD2+/CD5+/CD1-/CD3-). Transcripts of the CD3-delta and CD3 epsilon genes were present in all CD3- and CD3+ T-ALL tested, including prothymocytic T-ALL. However, prothymocytic T-ALL had germline TcR-beta genes and were not rearranged to the characterized TcR-gamma joining regions. The presence of CD3 transcripts and absence of TcR gene rearrangements in prothymocytic T-ALL supports their immature T cell character. Two immature thymocytic T-ALL also had germline TcR-gamma genes and one of them had germline TcR-beta genes. In all other T-ALL the TcR-gamma and TcR-beta genes were rearranged. The presumptive functional 1.3-kilobase TcR-beta transcripts were detected in the majority of T ALL with rearranged TcR-beta genes. Distinct levels of TcR-gamma transcripts appeared to be present only in some thymocytic T-ALL, i.e., some immature thymocytic T-ALL and common thymocytic T-ALL. TcR-alpha mRNA could only be detected in CD3+ mature T-ALL, but was absent in all CD3+ common thymocytic T-ALL tested. Our data indicate that CD3 gene transcription is one of the earliest events during T cell differentiation and already occurs in prothymocytes. The TcR gamma and TcR-beta genes rearrange early during thymocytic differentiation and can subsequently be transcribed. High levels of TcR-gamma gene transcription may only occur in a part of the T cells during thymic differentiation, while TcR-beta gene transcription continues during further differentiation. TcR-alpha gene transcription may be the final step in the production of the complete set of TcR and CD3 proteins, resulting in the expression of the TcR alpha beta-CD3 complex at the cell surface of mature T cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3100633 TI - Phenotypic and functional characterization of recombinant interleukin 2 (rIL 2) induced activated killer cells: analysis at the population and clonal levels. AB - In these studies we investigated the phenotypic and functional characteristics of human rIL 2-activated killer cells (LAK). By FACS sorting we separated PBL into Leu-11- and Leu-11+ cell fractions and cultured them for 4 days in 100 U/ml rIL 2. Under these culture conditions, cells of the Leu-11+ fraction acquired a stronger LAK activity against fresh autologous or allogeneic melanoma cells as compared with Leu-11- cells or unfractionated PBL. To better characterize the cells responsible for this cytolytic activity, we directly cloned Leu-11+ and Leu 11- FACS-sorted cells in the presence of 1% PHA, irradiated spleen feeder cells, and rIL 2. From 6 to 10% of the Leu-11+ cells and from 42 to 66% of the Leu-11- cells plated gave rise to clonal progenies that were tested simultaneously for cytolytic activity against fresh melanoma cells and NK-sensitive K562 target cells in a 4-hr 51Cr-release assay. Most of the Leu-11+ microcultures lysed fresh melanoma target cells (35 out of 38 and 26 out of 34 in two separate experiments), whereas only a few clones derived from the Leu-11- cell fraction had this capability (four out of 45 and one out of 41). All the clones lysing fresh melanoma cells also efficiently killed K562 target cells, whereas other clones lysing only K562 could be found among Leu-11+ and Leu-11- clones. Nine clones expressing LAK activity were tested for their reactivity against a panel of different tumor target cells. All clones were able to lyse a broad panel of target cells including NK-sensitive and NK-resistant cultured or noncultured human tumor target cells, as well as mouse tumor cell lines. Surface marker analysis of 14 clones displaying LAK activity, all derived from Leu-11+ cells, showed that they were all T3 (CD3)-, whereas 10 out of 14 expressed the T11 (CD2) antigen and only four were weakly stained by an anti-T8 (CD8) mAb. All 14 clones expressed the T40 (CD7) T cell marker and DR and LFA-1 antigens. Cytolysis inhibition experiments performed on a rIL 2-activated Leu-11+ population and on two LAK cell clones, both expressing T11 antigen, showed that anti-LFA-1 but not anti-T11 mAb could inhibit cytolysis of freshly derived tumor target cells. PMID- 3100632 TI - Germ-line affinity and germ-line variable-region genes in the B cell response. AB - The predominance of germ-line genes in IgM expression was evaluated from the nucleotide sequences of mRNA, derived from 10 hybridoma cell lines, coding for the VH and VL regions of anti-5-dimethylaminonaphthalene-1-sulfonyl (anti-Dns) IgM antibody. At least six germ-line VH gene segments distributed among four families are used in this response. Seven of the 10 independently rear-ranged VH genes were identified as germ line, with the other three possibly germ line. In all of them the D and JH portions retained the germ-line sequences of the D and JH segments from which they were derived. Maximum diversity was found in the D segments and the use of noncoded nucleotides at the VH-D and D-JH junctions. Of the eight cell lines expressing the lambda light chains, all were germ line and involved the three subtypes. Maximum affinity for the homologous ligand was found among the seven cell lines identified as expressing germ-line gene segments. Thus any somatic mutation among the remaining 3 cell lines did not provide enhanced affinity and the observed affinity of each cell line can be described as germ line affinity. It is further suggested that the anti-Dns selectivity of the IgM antibodies is associated primarily with the CDR3 regions. PMID- 3100634 TI - The third component of complement (C3) bound to tumor target cells enhances their sensitivity to killing by activated macrophages. AB - The third component of complement (C3) bound to P815 tumor cells enhanced their susceptibility to killing by Corynebacterium parvum-activated murine macrophages (M phi). Hemolytically active normal mouse serum and C5-deficient mouse serum were used to deposit complement (C) on P815 tumor cells, in the absence of exogenous antibody, by an alternative pathway mechanism. Cell-bound C3 was detected and was quantified by using a cellular enzyme-linked immunospecific assay. Activated M phi produced tumor cytolysis in a serum-free 16-hr 51Cr release assay. The lysis of C-treated tumor cells was increased over targets treated with sera containing 10 mM EDTA, heat-inactivated mouse sera, or medium. In addition, C alone did not cause specific 51Cr release. M phi elicited by casein or PBS did not lyse any of the tumor targets tested. The increase in lysis was dependent on the dilution of serum used, and was strongly correlated with the amount of C3 detected on the tumor cells. The enhanced lysis was abrogated by incubating C3-bearing tumor cells with F(ab')2 fragments of a goat anti-mouse C3 antibody. C treatment did not alter the kinetics of tumor cell lysis, nor did it enhance the binding of the targets to effector cells. These results suggest that C may regulate M phi-mediated killing of tumor cells by increasing the lytic efficiency of M phi that are in contact with target-bound C3. PMID- 3100635 TI - Immunochemical and functional analysis of HLA class II antigens induced by recombinant immune interferon on normal epidermal melanocytes. AB - The effect of recombinant immune interferon (IFN-gamma) on the expression and shedding of HLA antigens and of melanoma-associated antigens (MAA) by epidermal melanocytes was investigated by using serologic and immunochemical techniques. IFN-gamma enhances the expression and/or shedding of HLA class I antigens and of the cytoplasmic MAA defined by monoclonal antibody (MoAb) 465.12S and induces a slight reduction in the expression of the high m.w. melanoma-associated antigen (HMW-MAA). In agreement with the data in the literature, melanocytes incubated with IFN-gamma acquire HLA-DR, -DQ, and -DP antigens. Contrary to previous information in the literature, the effect is not restricted to HLA class II antigens, since IFN-gamma also induces the expression of the 96-kDa MAA recognized by MoAb CL203. The effect of IFN-gamma on HLA class II antigens and 96 kDa MAA is dose and time dependent and is specific, because recombinant leukocyte interferon affects the expression of neither type of antigen. In spite of the expression of HLA class II antigens, IFN-gamma-treated melanocytes do not acquire the ability to stimulate the proliferation of allogeneic lymphocytes. HLA-DR antigens are more susceptible to induction by IFN-gamma than HLA-DQ and -DP antigens, since the percentage of melanocytes acquiring HLA-DQ and -DP antigens is lower than that acquiring HLA-DR antigens. Furthermore, the dose of IFN-gamma is higher and the time of incubation is longer to induce HLA-DQ and -DP antigens than to induce HLA-DR antigens. The differential susceptibility of HLA-DR, -DQ, and -DP antigens as well as of melanocytes from various donors to the modulating effect of IFN-gamma may provide an explanation for the more frequent detection of HLA-DR than of HLA-DQ and -DP antigens in melanoma lesions and for the expression of HLA class II antigens by some, but not all, melanoma lesions. PMID- 3100636 TI - Lack of IL 2-dependent proliferation despite significant expression of high affinity IL 2 receptor on murine cytolytic T lymphocyte clones late after antigenic stimulation. AB - In this study, we examine the expression of IL 2 receptors on class I and class II MHC-restricted, influenza-specific murine T lymphocyte clones at early (day 3) and late (day 8 to day 12) times after antigenic stimulation. IL 2 receptor expression on the three clones examined increases to peak levels early and subsequently decays 10-fold to 50-fold during this time period, as evidenced by monoclonal anti-IL 2 receptor antibody binding. However, in IL 2 binding site studies these clones retain high levels of high-affinity IL 2 receptors (46 to 97% of day 3 levels) at the later time points, despite their inability to proliferate in response to IL 2 in the form of supernatant from Con A-stimulated rat splenocytes. Considerable clone to clone variation is seen in binding site affinity for IL 2, whereas no significant change in binding affinity for IL 2 is exhibited for a particular clone as a function of time after activation, suggesting little structural change in the IL 2 receptor with time. Contrary to this finding, Con A-stimulated murine splenocytes exhibit a sharp decay in IL 2 receptor expression reaching 25% of peak (day 3) levels by day 10 after stimulation by lectin, with a significant decrease in the average binding site affinity for IL 2 in the population. This change in affinity in the Con A stimulated population may, however, reflect a selection with time for lymphocytes with lower affinity for IL 2. To elucidate where the potential block may be that prevents these CTL clones from proliferating in an IL 2-dependent manner, the ability of the cells to internalize bound IL 2 at late times after activation is examined. All three clones late after activation are able to internalize bound IL 2 with efficiencies equivalent to that seen at day 3. Additionally, two of the three clones late after activation are able to upregulate expression of IL 2 receptors in response to picamolar concentrations of IL 2, indicating that the receptors on these clones are able to transmit a signal, although insufficient to induce proliferation of the cells. These observations strongly suggest that for the CTL clones examined, at late times after antigenic stimulation, engagement of IL 2 by the high-affinity receptor is not a sufficient signal to induce cells to transit through the cell cycle. PMID- 3100637 TI - A novel pathway of human T cell activation via a 103 kD T cell activation antigen. AB - A novel triggering signal for human proliferating and cytotoxic T lymphocytes defined by a 103 kD T cell-specific activation antigen (Tp103) is described. Tp103 is expressed on all proliferating normal T cells but is not present, or present only in low amounts, on resting peripheral blood T lymphocytes. Cross linking of T cell and Fc receptor-positive accessory or target cells by an antibody against Tp103 leads to activation of the T cell. The proliferative response is due to an autocrine IL 2-dependent mechanism and can be inhibited by antibodies against the IL 2 receptor or by Cyclosporin A. Resting Tp103-positive T cells also respond to anti-Tp103. Although Tp103 is not linked to the antigen receptor/T3 complex, triggering via Tp103 can be inhibited by modulation of the T3 molecule. Thus, Tp103 defines a new antigen-independent pathway of T cell activation that can be regulated via other T cell surface structures. PMID- 3100638 TI - Modulation of CD4 by antigenic activation. AB - Cell surface expression of CD4, an invariant membrane glycoprotein, is characteristic of the MHC class II-restricted T cell helper/inducer subset. Although the specificity and restriction patterns of T lymphocytes are determined by the T cell receptor for antigen, CD4 might represent an additional "interaction" molecule that is required to strengthen the interaction between T cells, antigen, and antigen-presenting cells. In this manuscript, we have shown that the cell surface expression of CD4 is correlated with activation of T cells. Data presented in this paper have demonstrated, for the first time, that antigenic stimulation of human T cell clones caused a decrease in the expression of the CD4 marker (as well as to the CD3 marker) to about 50% of the constitutive level. As previously demonstrated, PMA caused modulation of CD4 and CD3, which suggested that phosphorylation by protein kinase C played a crucial role in the regulation of the expression of both markers. The parallel down-regulation of CD3 and CD4 after antigen stimulation suggested that both markers might be members of a multimolecular complex mediating T cell activation. PMID- 3100639 TI - Evidence for negative regulation of T cell growth by low affinity interleukin 2 receptors. AB - Two experimental situations have been studied, and the results provide evidence for a negative regulatory role for the low affinity interleukin 2 receptor (LA-IL 2R). The IL 2-dependent T helper cell line L-14, deprived of IL 2, becomes quiescent and expresses comparable numbers of high affinity IL 2R (HA-IL 2R) and LA-IL 2R. After activation by recombinant IL 2, this cell line preferentially expresses LA-IL 2R. The IL 2 responsiveness of the L-14 cell line was found to vary according to the ratio of LA-IL 2R to HA-IL 2R: the relative predominance of the LA-IL 2R coincides with a hyporeactivity of cells to IL 2. In contrast, a predominance of HA-IL 2R is accompanied by an increase in cellular IL 2 reactivity. Treatment of three IL 2-dependent T cell lines (L-14, HT-2, and C30.1) with limited amounts of recombinant IL 2 and moderate concentrations of anti-IL 2R monoclonal antibodies stimulates T cell growth. This treatment was shown to selectively diminish the expression of membrane LA-IL 2R. The stimulation was attributed to the decrease of expression of LA-IL 2R. PMID- 3100641 TI - Species-specific variations in the molecular heterogeneity of the platelet activating factor. AB - The molecular heterogeneity of platelet-activating factor (PAF) synthesized by unstimulated and Ca2+ ionophore (A23187)-stimulated PMN from rat, mouse, and guinea pig and by rat basophilic leukemia (RBL) cells was investigated by gas chromatography-negative ion chemical ionization mass spectrometry. Several molecular species of PAF ranging from C14:0 to C19:0 were detected in all of the cells studied. PAF produced by each cell type exhibited a unique pattern of molecular species distribution. Although C16:0 was the major PAF molecular species of rat PMN and RBL cells representing 96% and 85% of the total PAF, respectively, PAF from mice PMN contained 81% of C16:0, 10% of C18:1, and 6% of C18:0. Alternatively, A23187-stimulated guinea pig PMN yielded PAF molecular species 35% in C16:0, 35% in C17:0, 8% in C18:1, and 3% in C18:0. Small but significant differences in the PAF molecular species distribution of resting and ionophore stimulated cells were also observed. In contrast to the PAF molecular species composition, the precursor 1-O-alkyl-2-acyl-glycero-3-phosphocholine of all the cell types was predominantly hexadecyl (C16:0) alkyl chain in the sn-1 position, representing 60 to 80% of the total 1-O-alkyl-2-acyl-glycero-3 phosphocholine. Thus, these results not only indicate a high degree of selectivity for utilization of precursor substrates for PAF biosynthesis, but also demonstrate that the selectivity is species specific. PMID- 3100640 TI - Diacylglycerol mass measurements in stimulated HL-60 phagocytes. AB - The mass of sn-1,2-diacylglycerol in crude lipid extracts from differentiated HL 60 phagocytes was measured by quantitative conversion of the diacylglycerol to [32P]-labeled phosphatidic acid catalyzed by E. coli diacylglycerol kinase. The chemotactic peptide N-formyl-Met-Leu-Phe caused a time- and concentration dependent increase in diacylglycerol that was maximal at 4 min. Diacylglycerol returned toward basal levels by 15 min. The basal level of diacylglycerol was 290 +/- 25 pmol/10(7) cells (n = 36). Maximally effective concentrations of N-formyl Met-Leu-Phe and N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys increased diacylglycerol to 176% +/- 16 of basal (n = 8) and 198% +/- 15 of basal (n = 4), respectively. t-Boc-Phe Leu-Phe-Leu-Phe, a competitive antagonist of formyl peptide receptor function, competitively inhibited the N-formyl-Met-Leu-Phe-induced diacylglycerol increase. Pretreatment of the cells with pertussis toxin abolished the stimulated rise in diacylglycerol, whereas depletion of extracellular Ca2+ markedly inhibited the increase. The Ca2+ ionophore A23187 stimulated a large (450% of basal) and persistent (greater than 30 min) increase in diacylglycerol. These data suggest that agents which raise intracellular Ca2+ levels in differentiated HL-60 cells produce a prolonged increase in cellular diacylglycerol which may activate protein kinase C. PMID- 3100642 TI - Fibroblast stimulation in schistosomiasis. VII. Egg granulomas secrete factors that stimulate collagen and fibronectin synthesis. AB - Tissue fibrosis in schistosomiasis is largely responsible for the important morbidity that results from infection with the trematode worms, Schistosoma. Neither the migrating larval forms (cercariae) nor the intravascular adult worms appear to incite pathological responses that are important in chronic schistosomiasis. On the other hand, eggs deposited in tissue incite chronic granulomatous inflammatory responses that are the hallmark of infection and precede the onset of adjacent tissue fibrosis. We previously reported that products of the egg granulomas can stimulate a number of relevant responses in fibroblast cultures that in vivo would be expected to promote tissue fibrosis. We report here that the granulomas secrete factors that in vitro can stimulate collagen and fibronectin synthesis in fibroblasts. We determined that activity stimulating collagen synthesis is congruent to 10 Kd (gel filtration) with a pI of congruent to 5.5 (isoelectric focusing); additional activity is also detected in some other fractions (congruent to Kd; pI approximately 7.0). In contrast, the activity stimulating fibronectin synthesis was congruent to 22 Kd with a pI of 5.5. Activity was also present in fractions of 50 Kd with pI of approximately 7.5. Fibroblasts grown in granuloma supernatant-containing medium contained greater steady-state levels of specific mRNA coding for type I procollagen and fibronectin compared with cells cultured in unsupplemented medium. These observations support the hypothesis that biologically active molecules secreted by granuloma cells are instrumental in the initiation of tissue fibrosis in schistosomiasis. PMID- 3100643 TI - Highly preferential VH-VL pairing in normal B cells results in antigen independent selection of the available repertoire. AB - The aim of this work was to analyze the probabilities of combined expression of the various polymorphic forms of two well-defined VH and VK segments. The availability of two monoclonal antibodies specific, respectively, for the VHT15 and VK21 D-E gene products allowed us to study, both in the selected and in the preimmune repertoire, the expression of VHT15-VK21 D-E pairs in several mouse strains. Our data establish, first, that even before antigen encounters B cells, clones utilize a highly biased repertoire of VH-VL combinations and, secondly, that the level of productive VH-VL pairing depends primarily on the "allelic" form of the relevant VH and VK genes. Furthermore, clonal analysis revealed that this asymmetry in Ig gene expression affects a large proportion of newly arising B cells. Together, these studies demand reconsideration of the current estimates of the available antibody repertoire size, and provide new insights for our understanding of the phenomenon of clonal dominance. PMID- 3100644 TI - Functional analogues of the VKOx1 gene in different strains of mice: evolutionary conservation but diversity based on V-J joining. AB - Monoclonal antibodies to the hapten phenyloxazolone were raised 7 days after immunization in mice of six strains (BALB/c, C57BL-Igha, DBA2, RF, A/J, and CE). Hybridomas were selected that produced 260 idiotype-positive antibodies, and their light chain mRNA were partially sequenced. (RF is an idiotype-negative strain, and sequencing was done without this selection.) All newly sequenced BALB/c, C57BL-Igha, DBA/2, A/J, or CE VK segments had a 100% nucleotide homology with the VKOx1 (H3) germline gene. This gene codes for one third of early BALB/c phenyloxazolone antibodies, and according to our results the same gene has a significant role in the early response of at least five strains of mice. Four RF hybridomas had identical nucleotide sequences, suggesting that they express a non mutated nucleotide sequence of a new VK germ-line gene (VKOx2). This gene codes for a CDR1 which is two amino acids longer than the CDR1 coded by the VKOx1 gene, but otherwise the two genes are related (94.5% sequence homology). All but one of the 16 kappa chains studied had the J5 segment; this segment had the same sequence in all six strains. One RF antibody had the J4 segment the nucleotide sequence of which differs from the BALB/c J4 segment in two places. Three of the kappa chains had an extra long CDR3. Long and "normal" kappa chains were probably coded by the same pair of germ-line genes (VKOx1 and J5, or VKOx2 and J5). The length heterogeneity was probably caused by a lack of precision in VK-JK joining. PMID- 3100645 TI - Comparison of different sandwich enzyme immunoassays for the quantitation of human apolipoproteins A-I and A-II. AB - Variants of a non-competitive enzyme immunoassay for human apolipoproteins A-I and A-II are described. The method developed is highly sensitive and highly specific. There is a good correlation between the reference technique (electroimmunoassay) and both apolipoprotein A-I and A-II assays (r=0.92). For the apolipoprotein A-I assay, seven simple treatments were studied. Two of these treatments (plasma plus Tween 20 and serum plus apo A-II) greatly increased the precision and the accuracy of the results. For the apo A-II measurement, no treatment of the samples is necessary, but plasma should be preferentially used rather than serum. PMID- 3100646 TI - Removal of endogenous peroxidase activity from cryostat sections for immunoperoxidase visualisation of monoclonal antibodies. AB - The interpretation of immunoperoxidase staining of frozen tissue sections can be severely limited by the presence of endogenous peroxidase enzymes in the tissue. Previously recommended methods of reducing this enzyme activity were examined, but were found to be unsatisfactory when applied to the small intestine. A method, which effectively eliminates this background staining but which does not interfere with the binding of monoclonal antibodies to various tissue components, is described. This method may prove useful in immunoperoxidase studies of other tissues in which high levels of endogenous peroxidase are present. PMID- 3100647 TI - A simple microassay for interleukin-2 activity. AB - A simple in vitro assay is described to quantitate human interleukin-2 (IL-2). It is based on the spontaneous' activation of human peripheral T cells in tissue culture and the subsequent expression of the IL-2 receptor. The results obtained with this assay agree with those of assays which utilise IL-2 dependent T cell clones. The method is highly sensitive, reproducible and easy to perform. PMID- 3100648 TI - Production and characterization of a rabbit antiserum to the mouse CD8 antigenic complex by immunization with a synthetic peptide. AB - A rabbit antiserum to the mouse CD8 antigen (Lyt-2/3) was obtained through the use of a synthetic peptide corresponding to the N-terminal segment of the 37 kDa subunit of the CD8 molecular complex. This anti-peptide antiserum detected specifically the membrane antigen from detergent extracts of surface-labeled mouse thymocytes. The efficiency of the immunoprecipitation increased significantly upon treatment of the cell lysates with 0.1% SDS at 100 degrees C before immunopurification. Finally both the 37 kDa and the 32 kDa polypeptides expressing the Lyt-2 antigen were revealed by immunoblotting. PMID- 3100649 TI - Improved detection of anti-Jo-1 antibody, a marker for myositis, using purified histidyl-tRNA synthetase. AB - The increased detection of anti-Jo-1 antibody afforded by the use of the purified antigen, histidyl-tRNA synthetase, in counterimmunoelectrophoresis is demonstrated. Using purified antigen, anti-Jo-1 antibody was detected in the sera of 16/33 (48.5%) patients with confirmed myositis and in 20/45 (44.5%) patients with confirmed or possible myositis. This rate is approximately double that obtained with commercial thymus extracts both in this study and seven others reported in the literature. The presence of antibody shows marked correlation with the activity of myositis at the time of serum sampling and with the presence of interstitial lung disease. Detection rates are similar in patients with polymyositis and dermatomyositis both with and without additional connective tissue diseases. PMID- 3100650 TI - A monoclonal antibody may show cross-reactivities in Ouchterlony assays but not in other assays. AB - A monoclonal antibody to human IgG was tested with myeloma proteins of the four IgG subclasses. When tested by immunofluorometric assay, enzyme-linked immunosorbent assay, hemagglutination and hemagglutination inhibition assays, the antibody reacted with IgG3 but not with the other three IgG subclasses. When tested by Ouchterlony assays in the presence of polyethylene glycol, the antibody formed lines with all four IgG proteins. The line with IgG3 was sharp and stable, but the lines with the other three IgG subclasses tended to blur with time and with the lower PEG concentrations. These findings show that Ouchterlony assays can reveal cross-reactions of a monoclonal antibody that can be missed by more sensitive assays. PMID- 3100651 TI - Re: Application of double immunohistologic staining with monoclonal antibodies in lymph node pathology. PMID- 3100652 TI - Modulation of arachidonic acid metabolism in a cultured newborn rat keratinocyte cell line. AB - Newborn rat keratinocytes, the NBR cell line, synthesized the cyclooxygenase metabolic products, prostaglandins E2 and F2 alpha, and the lipoxygenase metabolic product, hydroxyeicosatetraenoic acid. This metabolism was stimulated by incubation of the cells with the Ca++ ionophore, A23187; melittin; bradykinin; recombinant human f-met epidermal growth factor; the tumor promoter, 12-O tetradecanoylphorbol-13-acetate; and the synthetic analog of diacylglycerol, 1 oleoyl-2-acetyl glycerol. Production of the cyclooxygenase products was inhibited by the synthetic glucocorticoid, dexamethasone. The stimulation appeared to be modulated by deesterification of arachidonic acid from the cellular lipids, presumably by phospholipase A2. Increased intracellular levels of Ca++ and phosphorylating activities that result from polyphosphoinositol turnover as well as phosphorylating activities independent of phosphatidylinositol turnover appear to be regulating phospholipase A2 hydrolysis of phospholipids. PMID- 3100653 TI - Epidermal cell-derived lymphocyte differentiating factor (ELDIF) inhibits in vitro lymphoproliferative responses and interleukin 2 production. AB - We have examined the biologic characteristics and immunologic properties of epidermal cell-derived lymphocyte differentiating factor (ELDIF), a lymphocyte differentiating factor produced by cultured human keratinocytes. The ELDIF was semipurified by a gel filtration procedure. This factor, which is distinct from prostaglandins, epidermal cell-derived thymocyte activating factor (ETAF), and the well-known thymic hormones (thymulin, thymopoietin, and thymosin alpha 1) did not exhibit any interleukin (IL)-1, IL-2, or IL-3 activity. It strongly inhibited in vitro lymphoproliferative responses of normal mouse spleen cells to phytohemagglutinin, concanavalin A, and lipopolysaccharide. This dose-dependent phenomenon was associated with a suppression of IL-2 production rather than any toxic effect. It can be concluded that ELDIF, a product of human epidermal cells, which displays in vitro T-cell differentiation and regulatory activities, could be of major importance in vivo in the control of cutaneous inflammatory reactions. PMID- 3100654 TI - L-serine potentiates the mitogenic effects of growth factors on cultured human keratinocytes. AB - L-Serine increased the growth of passaged human foreskin keratinocytes in terms of DNA and protein per dish of cells, and potentiated the mitogenic effects of serum and epidermal growth factor, and also insulin, keratinocyte growth factor, and a bovine pituitary extract. The effects of serine were apparent with as little as 0.05 mM. The stimulatory effects of these various growth factors were additive, without synergism. Exposure to L-[3H]serine resulted in labeling of the phospholipids phosphatidyl (Ptd) serine, Ptd ethanolamine, sphingomyelin, and, to a slight extent, Ptd choline. The time course of labeling suggested synthesis of Ptd serine was initiated; Ptd serine was converted to Ptd ethanolamine; little methylation of Ptd ethanolamine to form Ptd choline took place. Separation of nonradioactive phospholipids and phosphorus assay of individual lipids showed that serine-supplemented cells had only slightly increased content of Ptd serine and Ptd ethanolamine. The significance of these for activation of protein kinase C is discussed. PMID- 3100655 TI - Glycosaminoglycan synthesis by proliferating and differentiated human keratinocytes in culture. AB - Glycosaminoglycan (GAG) synthesis and compartmentalization were studied in populations of human neonatal keratinocytes under conditions of proliferation and terminal differentiation in vitro. Following isotopic labeling with the precursors [3H]glucosamine and [35S]sulfate, GAGs were extracted from the keratinocytes into several operationally created compartments associated with the cells and extracellular matrix. Chondroitin sulfate and heparan sulfate accounted for the majority of the incorporated label in all preparations. Although total sulfated GAGs per culture increased from proliferative to differentiated conditions, GAG content normalized to the DNA content of the cultures demonstrated the reverse trend. This was particularly evident for the chondroitin sulfates, which declined 60-70% in the differentiated cultures. Furthermore, label incorporation into chondroitin and heparan sulfates revealed a relative compartmental shift to a trypsin-accessible site upon keratinocyte differentiation. An analysis of heparan sulfate structure by characterization of the oligosaccharide products resulting from low pH nitrous acid deaminative degradation provided evidence that the parent material from differentiated keratinocytes contains a larger region of N-sulfated glucosamine residues unassociated with ester sulfate groups. The correlation of variations in GAG content and compartmentalization with the growth condition of human keratinocytes constitutes evidence that this heterogeneous group of cell surface-associated carbohydrates is involved in some aspect of cell function associated with growth control or differentiation. Furthermore, the apparent differences in heparan sulfate primary structure indicate that there is structure-function specificity to this association. PMID- 3100657 TI - Clinical trials and statistical rigor--are the benefits necessarily worth the cost? PMID- 3100656 TI - Epidermal Langerhans cells--a target for HTLV-III/LAV infection. AB - Langerhans cells (LC) are bone marrow-derived, Ia+, CD1+, CD4+, ATPase+ dendritic antigen-presenting cells within the human epidermis. Since the CD4 molecule has been implicated as a receptor structure for HTLV-III/LAV (human T-cell leukemia virus/lymphadenopathy-associated virus), we asked whether LC from HTLV-III/LAV seropositive individuals display signs of HTLV-III/LAV infection. In skin biopsies from 7/40 HTLV-III/LAV-infected persons (1 asymptomatic carrier, 2 patients with acquired immunodeficiency syndrome (AIDS)-related complex and 4 patients with AIDS), LC were the only epidermal cells to react with a monoclonal antibody specific for the HTLV-III core protein p17. A varying percentage of p17+ LC were morphologically altered with blunt dendrites and poorly demarcated cellular contours. In one of these biopsies, the presence of LC-associated viral particles characteristic of HTLV-III/LAV as well as cytopathic changes in approximately one-third of the LC population were demonstrated by electron microscopy. These results strongly suggest that LC may harbor HTLV-III/LAV. The infection of LC with this retrovirus may have deleterious consequences for the immunologic functions of this cell system and may thus contribute to both the acquisition of immunodeficiency and the infectious and neoplastic complications of AIDS. PMID- 3100658 TI - Serological tests for blastomycosis: assessments during a large point-source outbreak in Wisconsin. AB - Enzyme immunoassay (EIA), immunodiffusion (ID), and complement fixation (CF) tests for antibody to the A antigen of Blastomyces dermatitidis were assessed in 47 patients in an epidemic of blastomycosis and in 89 control subjects with lower respiratory tract illness. Antibody was detected by EIA, ID, and CF in 77%, 28%, and 9% of the patients, respectively. EIA titers ranged from 1:8-1:512 (median titer, 1:128). Antibody detected by ID or CF was always detectable by EIA. Antibody was detected by EIA 13 days after illness onset, and the peak seroprevalence rate and geometric mean titer occurred 50-70 days after onset. Antifungal therapy produced a significant decline in antibody titer by approximately six months after onset. Seven (8%) control subjects had detectable antibody, six had EIA titers of 1:8, and one had a titer of 1:16. The specificities for EIA, ID, and CF were 92%, 100%, and 100%, respectively. The EIA provides a significant advance in serodiagnostic testing for blastomycosis and can be used in an outbreak setting as an epidemiological tool to identify acute B. dermatitidis infection; titers greater than or equal to 1:32 strongly support the diagnosis, whereas titers of 1:8 or 1:16 are suggestive. PMID- 3100659 TI - Association of meningococcal serotypes with the course of disease: serotypes 2a and 2b in the Netherlands, 1959-1981. AB - Case histories of 692 patients with meningococcal disease due to serogroup B, C, or W (W-135) were reviewed to study the association of the serotypes 2a and 2b with the course of disease. The case-fatality rate in group B disease was significantly associated with serotype 2b (B:2b) strains (P = 0.03). Age and year of admission did not account for this association. Septicemia was also found more frequently with B:2b than with other B serotypes, but neurological complications and sequelae were not. Neither C:2a nor W:2a was associated with a higher case fatality rate, with more cases of septicemia, or with more sequelae than were other C or W serotypes. We concluded that the 2b antigen, although not likely a causal factor, is a virulence marker among group B strains and that the protective effect of a vaccine containing this protein (among others) needs to be studied. PMID- 3100660 TI - Direct invasion of the central nervous system by Mycoplasma pneumoniae: a report of two cases. AB - We studied two patients with involvement of the central nervous system (CNS) associated with Mycoplasma pneumoniae. One patient had encephalitis and acute cerebellar ataxia, whereas the second had a mixed picture of encephalitic reaction superimposed on a disseminated malignancy of unknown origin. Specific IgM antibodies to M. pneumoniae were detected in the patients' sera but not in their cerebrospinal fluid. M. pneumoniae was repeatedly isolated by cultures from throat swabs and cerebrospinal fluid samples from both patients. Our patients add to previous reports suggesting that CNS involvement may result from direct invasion of the CNS by the pathogen. PMID- 3100662 TI - Increased specificity of serodiagnosis of Chagas' disease by detection of antibody to the 72- and 90-kilodalton glycoproteins of Trypanosoma cruzi. PMID- 3100661 TI - Dose response of experimental Pseudomonas endophthalmitis to ciprofloxacin, gentamicin, and imipenem: evidence for resistance to "late" treatment of infections. AB - Single intravitreal doses of ciprofloxacin, gentamicin, or imipenem were administered to rabbits with pseudomonas endophthalmitis for determination of the maximally effective dose. Treatment was given 24 hr ("early") or 48 hr ("late") after infection. With early treatment the dose-response relationship between the drug concentration and the diminution in bacterial counts in the vitreous humor was linear with all three drugs. By contrast, with late treatment the same vitreal concentrations had no significant effect on bacterial counts. The failure of late treatment was not due to an increased rate of clearance of drugs from the eyes and could not be reproduced with a similar bacterial inoculum in vitro. Bacteria cultured from treated eyes were fully sensitive when plated directly onto drug-containing agar. The poor bactericidal effect of late treatment may in part be related to transient phenotypic alterations in the bacteria in response to changes in the environment of infection such as hypoxia, low pH, and exhaustion of critical bacterial nutrients. PMID- 3100663 TI - In vitro activation of the antibacterial activity of human pulmonary macrophages by recombinant gamma interferon. PMID- 3100664 TI - Purification and further characterization of an anti-murine interferon-gamma monoclonal neutralizing antibody. AB - The R4-6A2 rat-mouse hybridoma, which secretes a rat IgG1 monoclonal antibody (MAb) capable of neutralizing murine interferon-gamma (MuIFN-gamma), was grown as ascites in athymic nude (nu/nu) mice. The neutralizing titers of ascitic fluids were 400 times higher than those of supernatants from R4-6A2 cultures. Moreover, the specific activities (MAb) neutralizing units/mg protein) of the ascitic fluids were much greater than those of R4-6A2 culture supernatants. Ascitic fluid MAb was purified by anion-exchange chromatography, with excellent recovery of applied neutralizing activity. The ability of the R4-6A2 anti-MuIFN-gamma MAb to neutralize several different activities of MuIFN-gamma was studied. The MAb neutralized the ability of MuIFN-gamma to inhibit the growth of cells (antiproliferative activity). The ability of MuIFN-gamma to render cells of a heterologous species (rat) resistant to viral replication was also neutralized by this MAb. The MAb-neutralizing titers for MuIFN-gamma antiviral activities, on both homologous (murine L929) and heterologous (rat fibroblast) cells, were inversely proportional to the antiviral activity titers on each cell type. PMID- 3100665 TI - Direct and cell-mediated effects of interferon-alpha and -gamma on cells chronically infected with HTLV-III. AB - The replication of the human T lymphotropic retrovirus HTLV-III in persistently infected cells is relatively insensitive to the direct antiviral action of human interferon-alpha or -gamma (IFN-alpha or -gamma), showing only a two- to threefold reduction of HTLV-III, even though the host cells are very sensitive to IFN, as shown by vesicular stomatitis virus (VSV)-yield reduction assay (4-5 log reduction of VSV). However, IFN anticellular activity is strongly enhanced in the presence of normal peripheral blood mononuclear cells, suggesting a cell-mediated effect of IFNs. PMID- 3100666 TI - Effects of interferons-alpha, -beta, and -gamma on human interleukin-2 production. AB - Interleukin-2 (IL-2) production was stimulated with staphylococcus enterotoxin A, heat-killed Staphylococcus aureus, or concanavalin A (ConA) in cultures of human peripheral blood mononuclear cells (PBMC). IL-2 was characterized by its effect on IL-2-dependent cytotoxic T lymphocytes (CTLL cells) and mouse thymocytes. Pretreatment of PBMC with greater than or equal to 100 IU/ml of human-alpha (HuIFN-alpha) or interferon-beta (HuIFN-beta), or with greater than or equal to 10 IU/ml HuIFN-gamma for 4 h enhanced the IL-2 production. The effects of 20-h IFN treatments were less pronounced or they exerted an inhibitory effect. Our results indicate that IFNs modulate IL-2 production, which in turn can mediate some of the immunomodulatory effects of IFNs. PMID- 3100667 TI - Regulatory effects on macrophages of human recombinant interferons-alpha. AB - The regulatory effects of human recombinant and hybrid interferons-alpha (IFN alpha) on macrophage-mediated tumoricidal activity were examined. Recombinant hybrid IFN-alpha-A/D suppressed the capacity of murine interferon-gamma (IFN gamma) to activate mouse peritoneal macrophages to a tumorilytic state, and blocked the killing of syngeneic syngeneic melanoma target cells by macrophages previously committed to the cytotoxic phenotype with a 4-h pretreatment with IFN gamma. This suppressive activity was limited to IFN-alpha-A/D, as IFN-alpha-A and IFN-alpha-D were not effective. In contrast, IFN-alpha-A, -D, and -A/D were all capable of activating human peripheral blood monocytes to lyse human tumor cells. When encapsulated in liposomes, only IFN-alpha-A/D maintained its monocyte activating efficacy. These findings suggest that the immunomodulatory effects of IFN-alpha subtypes and hybrid molecules are dependent on species of monocytes/macrophages, subtype, and nature of presentation to effector cells. PMID- 3100668 TI - Rigid internal fixation of mandibular fractures--an analysis of 45 patients treated according to the ASIF method. AB - A report is given of 45 patients with fractures of the mandible treated by the method of rigid internal fixation. In a majority of cases, there were either absolute or relative contraindications for an IMF. Most of the fractures plated were body fractures of the mandible, followed by angular, and symphysis fractures. In 4 cases, the fractures, caused by gunshots, were compound ones. In these, extensive soft tissue reconstructions were also performed. In a majority of the patients, good primary healing was observed, and the mean hospitalization time was only 4.4 days. The infection rate of 13% was, however, relatively high, and a few disturbances were seen with respect to motor and sensory function of the lower lip. Slight occlusal dysharmonies were registered in 23%, on an average of 22 weeks postoperatively, but these could be adjusted with a minimum of grinding. It was concluded that bone plating is a useful method in the treatment of several different types of mandibular fractures including the severe compound ones. The method can be especially recommended in cases in which an IMF is contraindicated or should be avoided. The possibilities for decreasing the frequency of postoperative infections are discussed. PMID- 3100669 TI - Periodontal healing after impacted lower third molar surgery. Precision and accuracy of radiographic assessment of intrabony defects. AB - The effect of periodontal tissues of impacted lower 3rd molar surgery has been investigated in a retrospective study comprising 215 cases, 2 years postoperatively. In order to evaluate the precision and accuracy of the radiographic assessment of intrabony defects on the distal surface of the lower 2nd molar using conventional free hand technique, a methodological study was performed on 25 patients. The error variance due to variability in the radiographic reproduction and examiner inconsistency was between 3 and 4% of the total variance. In order to evaluate the radiographic assessment of intrabony defects, intraoral radiographs were taken in the deepest part of the intrabony defect with and without a probe as an indicator. Comparing the 2 sets of radiographs, the deviation was 1 mm or less in 87.9% of the cases. The radiopaque marker enhanced the accuracy of assessment of intrabony defects to 96.7%. The study shows the intraoral freehand technique to be sufficiently reliable as regards radiographic reproduction of the mandibular molar area. It also demonstrates that the radiographic method describes the depth of postoperative intrabony defects on the distal surface of the lower 2nd molar more accurately than probing depth measurements alone. PMID- 3100670 TI - Reported symptoms, diseases, and medication of patients with orofacial discomfort complaints. AB - This paper is a part of a series of studies of 113 patients with orofacial and general complaints which they assumed were caused by metallic dental restorations and/or oral galvanic currents. An extensive case history was taken by means of a questionnaire and an interview. The results showed that the patients reported widely varying symptoms, both oral and general, such that the polysymptomatic character of the patients cannot be explained by a single etiologic factor. It is probable that many general factors, besides oral findings, alone or in combination, e.g. general health problems, side effects of medication, psycho social problems including stressful life events, and complications due to the chronicity of pain, may be associated with the oral and general complaints of these patients. PMID- 3100671 TI - Cysts of the nasopalatine duct. AB - Nasopalatine duct cysts in 70 patients were reexamined clinically and radiographically. 50 of them were also reexamined histopathologically. 20 specimens of normal duct tissue were likewise examined. More than half of the cysts showed clinical symptoms. The form on the radiograph was usually spherical or oval. Only 1 of 5 cysts was heart-shaped; 1 of 10 was unilateral. The mesiodistal width of the cysts ranged from 4-40 mm, with 75% from 6-12 mm. 3 of 4 showed pronounced radiolucency. Every 2nd cyst was completely surrounded by a thin radiopaque border. The histopathological investigation showed small cysts to be present in 1 of 4 clinically and radiographically normal nasopalatine ducts. More than 1 of 4 clinically and radiographically diagnosed cysts lacked histopathological characteristics of a cystic cavity. The type of epithelium in the cysts was independent of the vertical position in the duct. PMID- 3100672 TI - Changes in temporomandibular joint pain-dysfunction after surgical correction of dentofacial anomalies. AB - 20 patients with dentofacial anomalies were investigated with respect to signs and symptoms of temporomandibular joint pain-dysfunction, which was a common reason for requesting treatment. After surgical correction of the malocclusions, the patients were re-examined 1 week after removal of intermaxillary fixation (IMF), 6 months after surgery and, finally, after 1 to 2 1/2 years. Several of the patients complained of recurrent headaches before surgery and also reported several other subjective symptoms of temporomandibular joint pain-dysfunction. At final control, a statistically significant reduction in headache frequency, as well as for the anamnestic dysfunction index as a whole, was noted. An impairment of clinical signs of temporomandibular joint pain-dysfunction was noted 1 week after removal of IMF, but the situation then returned to that found preoperatively. At final control, a statistically significant reduction of the clinical dysfunction index used was noted. In line with other previous investigations, the patients were satisfied with the aesthetic result of the treatment. A statistically significant increase in number of occluding pairs of teeth was recorded postoperatively and the patients reported an improvement of chewing ability. It is concluded that surgical correction of dentofacial anomalies has a beneficial effect not only on aesthetic and dental occlusion but also upon signs and symptoms of temporomandibular joint pain-dysfunction. PMID- 3100673 TI - Arthroscopy of the temporomandibular joint. A clinical study. AB - Temporomandibular joint (TMJ) arthroscopy on 30 joints of 26 patients with different signs and symptoms of TMJ arthropathy was evaluated. Local anaesthesia was used and proved efficient. In 27 cases, the superior, and in 3 cases both, compartments were punctured. Successful examination was performed in 26 superior and 3 attempted inferior compartments. Functional impairment following arthroscopy was minor and rarely lasted more than one week. No postoperative bleeding, nerve damage, or infection was observed. Of the 2 systems tested, the rod-lens arthroscope showed superior optical quality. PMID- 3100674 TI - Presurgical planning for osseointegrated implants in the maxilla. A tomographic evaluation of available alveolar bone and morphological relations in the maxilla. AB - A clinical tomographic method of defining and demonstrating the hard and soft tissue morphology of those parts of the maxilla which are intended for osseointegrated implants is described. This preoperative examination is an useful aid in the choice and planning of the treatment as such, and in the decision concerning the calibre and position of the implants. Hence, it facilitates the surgical procedure. PMID- 3100675 TI - A single dose assessment of an ibuprofen/codeine combination in postoperative dental pain. AB - In a double-blind, single dose study of analgesic efficacy, 202 patients who had undergone lower 3rd molar extraction were divided into 5 groups to receive aspirin, placebo, ibuprofen, codeine, or an ibuprofen/codeine combination. Ibuprofen 200 mg (with or without codeine phosphate 15 mg) and aspirin 600 mg were significantly superior to either placebo or codeine phosphate 15 mg alone. Codeine phosphate at a dose of 15 mg was ineffective as an analgesic either alone or in combination. PMID- 3100676 TI - Mandibular versus inferior dental anaesthesia: clinical assessment of 3 different techniques. AB - Inferior dental anaesthesia via the direct intraoral approach, mandibular conduction anaesthesia via extraoral landmarks (Gow-Gates) and mandibular conduction anaesthesia via the tuberosity approach (Akinosi) were evaluated using onset and duration of anaesthesia, pain during injection, aspiration test, pinprick, depth and frequency of anaesthesia. 90 patients undergoing simple tooth extraction were randomly selected into 3 groups. They were given injections of 2 ml of 2% lidocaine with adrenaline (1:80,000). All techniques were mostly painless, none of them showing any special advantage in that sense. The differences in duration of anaesthesia among the applied techniques were insignificant. Positive aspirations were most frequently observed with the direct method of inferior dental anaesthesia, but this method gave the best result for the frequency of anaesthesia. After using the Gow-Gates method, the external branches of the buccal nerve were usually anaesthetized but the onset of anaesthesia was relatively slow. Mandibular conduction anaesthesia via the tuberosity approach did not show any particular advantage over the other 2 techniques in this investigation. A progress study is needed to determine more precisely the aspiration rate and frequency of anaesthesia for all the techniques. PMID- 3100677 TI - Foreign bodies of dental origin in the air and food passages. AB - 6 cases in which a reamer or a cast object was swallowed into the stomach or into the bronchus during dental treatment are described, with a review of the Japanese literature. The foreign bodies were removed by duodenotomy in one case, by endoscopic or bronchoscopic procedure in three cases; spontaneous evacuation in the stool occurred in two cases. The management of patients who swallowed a foreign body into the airway or into the alimentary canal is discussed. PMID- 3100678 TI - Teratogenesis of dexamethasone and preventive effect of vitamin B12. AB - Ddy mice which were treated with 0.32 mg of dexamethasone were used. Vitamin B12 was injected subcutaneously into the animals from the 10th day to the 13th day with a dosage of 0.1r, 1r, or 10r. The rate of incidence of cleft palate was decreased to 77.0% in the 0.1r group, 58.1% in the 1r group and 67.9% in the 10r group as compared to the control value of 88.5%. PMID- 3100679 TI - Accidental displacement of impacted maxillary third molars. AB - 3 cases of accidental displacement of maxillary impacted 3rd molars are presented. 2 were displaced into the maxillary sinus and 1 into the infratemporal fossa. The difficulties in locating these displaced teeth are described and demonstrated on a dry skull model. The mode of treatment is discussed. PMID- 3100680 TI - Diagnosis and treatment of the unicystic ameloblastoma. AB - Two cases of unicystic ameloblastoma are presented. The lesions were pain-free and expanded the mandible. They were removed by curettage. Recurrent lesions had similar clinical appearances and histological pictures compared to the original lesions. The unicystic ameloblastoma manifested itself as a cystic cavity without solid neoplastic features, which differs from the solid ameloblastoma with regard to the age of the patients and the rate of recurrence. The behavior of the unicystic ameloblastoma was similar to that of the primordial cyst. Despite the obvious risk of recurrence, conservative treatment with enucleation and curettage seemed to be justified in preference to mutilating radical surgery. PMID- 3100681 TI - Diffuse hyperplastic oncocytosis of the parotid gland. AB - This report concerns an extremely rare case of diffuse hyperplastic oncocytosis of the parotid gland occurring in a 60-year-old Japanese male. The clinical, macroscopical, and histopathological findings are presented and discussed. PMID- 3100682 TI - Large calculi of the submandibular salivary glands. AB - Salivary calculi occur in the submandibular and parotid glands, and their ducts, and occasionally reach a large size. However, little information is available on the composition of these giant stones. 2 cases are reported of unusually large calculi of the submandibular salivary glands. The glands were excised, and the results of chemical and infrared analysis of the calculi are presented. PMID- 3100683 TI - Malignant schwannoma of the mandible. AB - A case of malignant schwannoma occurring in the mandible of a 76-year-old Japanese woman is presented. Results of the gross examination are described as well as the surgical procedure. Details of the staining techniques for examination of the biopsy specimen are given. The histopathological findings are mentioned including those obtained from radiographic, microscopic, and electron microscopic examination. A discussion of the disease and of its difficulty of diagnosis follows. PMID- 3100684 TI - Combined curettage and cryosurgical treatment for the aggressive "giant cell lesion" of the mandible. AB - The treatment of an aggressive giant cell lesion of the mandible by combined curettage and cryosurgery is presented with a 5 year follow-up without recurrence. The difficulty in diagnosing and treating the more persistent central giant cell granulomas as compared to giant cell tumors of the jaws is discussed, and a more conservative first surgical approach is presented. PMID- 3100685 TI - Osteoma of the lateral pterygoid plate of the sphenoid bone. AB - A rare case is reported of an osteoma protruding into the pterygomandibular space from the lateral pterygoid plate of the sphenoid bone. The procedure of the diagnosis and treatment is described. In this case, computed tomography (CT) was the most useful in making a differential diagnosis. That the pulling force of the medial pterygoid muscle might be a causative agent in the growth of this osteoma is considered. PMID- 3100686 TI - Diagnostic and therapeutic problems of oral precancerous lesions. PMID- 3100687 TI - [Studies on bacteremias in cases with catheters placed for hemodialysis]. PMID- 3100688 TI - [Changes in serological responses against somatic O, heat-labile enterotoxin and colonization-factor antigen in patients with enterotoxigenic Escherichia coli infection]. PMID- 3100689 TI - [Outbreaks of food poisoning caused by enterotoxigenic Escherichia coli and detection of heat-labile enterotoxin in stools by an enzyme-linked immunosorbent assay]. PMID- 3100690 TI - [The analysis of background factors of pneumonia caused by opportunistic pathogens]. PMID- 3100691 TI - [The virulence of methicillin-resistant Staphylococcus aureus in mice]. PMID- 3100692 TI - [Evaluation of the in vitro activity of various antibiotics against Chlamydia trachomatis by indirect immunoperoxidase method]. PMID- 3100693 TI - [Clinical experience of 3 cases of toxic shock syndrome caused by methicillin cephem-resistant Staphylococcus aureus (MRSA)]. PMID- 3100694 TI - [A case of pneumonia associated with increased antibody titers to simultaneous Mycoplasma pneumoniae and Chlamydia psittaci]. PMID- 3100695 TI - [A case of acute myelogenous leukemia complicated with multiple liver abscesses caused by Candida albicans]. PMID- 3100696 TI - [Characterization of highly ampicillin-susceptible isolates of Pseudomonas aeruginosa]. PMID- 3100697 TI - [Rapid identification of bacteria in sputum and lung tissue in nosocomial pneumonia--fundamental study of indirect immunofluorescent staining by antibody to heat-killed antigens]. PMID- 3100698 TI - [Studies on tsutsugamushi disease in Gifu Prefecture. 3. Seasonal fluctuation in positive rates of Rickettsia tsutsugamushi in wild rodents and number of patients]. PMID- 3100699 TI - [Clinical evaluation of SMX/TMP in treatment of patients with malaria]. PMID- 3100700 TI - [Normal range of ADN-B (antideoxyribonuclease-B) titers in childhood--especially in children under 5 years old]. PMID- 3100701 TI - [Studies of experimental localized pneumonia associated with lung cancer]. PMID- 3100702 TI - [Comparative clinical study of T-2588 and cefaclor in chronic respiratory tract infections by a double-blind method]. PMID- 3100703 TI - [Comparative clinical study of T-2588 and bacampicillin in bacterial pneumonia by a double-blind method]. PMID- 3100704 TI - [Follicular development in pregnancy and the polycystic ovarian syndrome]. AB - In order to obtain some clues to the mechanism of follicular development, we studied sequential changes in circulatory hormone from spontaneous abortion up to the next ovulation in 11 women. In addition, morphological analysis of the follicles was performed in the ovarian tissue obtained from 4 pregnant women and another 4 women with polycystic ovarian syndrome (PCO). Blood was collected every 2-4 days and the serum samples were analyzed for HCG (LH), FSH, progesterone and estradiol by radioimmunoassay (RIA). Whole ovaries or the tissue obtained by ovarian wedge resection were sectioned serially at 2.5 micrometers. Every 13th slice was stained and examined under a light microscope. The present data were summarized as follows. A dominant follicle started to grow when LH.HCG levels declined to approximately 120 mIU l and FSH increased slightly. The largest nonatretic follicle seen in pregnancy or PCO was comparable with that seen in the late luteal phase of a normal cycle. The atretic rate of middle sized follicles (2.0 less than or equal to approximately less than 4.0 mm in diameter) was significantly higher in PCO than that seen in normal or pregnant women. These data indicate that the hormonal milieu of pregnancy or PCO does not interfere with the follicular development up to the stage of the largest nonatretic follicle seen in the late luteal phase of a normal cycle. This sized follicle grows to a dominant follicle within a short period under a minor stimulus by FSH. PMID- 3100705 TI - [Correlation of LH and prolactin pulses in normoprolactinemic women with ovulatory disturbances and variation of LH and FSH pulses and secreting capacity by administration of bromocriptine in the same cases]. AB - The difference between prolactin (PRL) basal levels on separate days in the 6 normoprolactinemic women--one case with an anovular cycle and 5 cases with 1 degree amenorrhea--among 14 normoprolactinemic women with ovulatory disturbances, showed significantly variation over 13 ng/ml within the normal range of the PRL basal level. PRL pulse frequencies of the same cases from 0900 h. to 1400 h. increased slightly compared with follicular phase. At the same time, the PRL pulse amplitudes were significantly higher than in the follicular phase but significantly lower than the PRL pulse amplitudes in hyperprolactinemic women. The net increase in PRL to TRH in the 6 cases was over 100 ng/ml. When the PRL net increase to TRH was over 100 ng/ml in normoprolactinemic women with ovulatory disturbances, the case is regarded as latent hyperprolactinemia. And 1 or 2 may be latent hyperprolactinemic syndrome. The LH/FSH basal level and delta LH/delta FSH to LH-RH before administration of bromocriptine increased in these cases compared with the follicular phase. During the administration of bromocriptine, the ratios decreased and approached the ratio in the follicular phase. The effect of clomid was improved by increased E2 in these cases. PMID- 3100706 TI - [Anterior pituitary hormone genes]. PMID- 3100707 TI - The value of the cervical score in monitoring ovulation induction for in vitro fertilization: a prospective double-blind study. AB - The present study was designed to determine the accuracy of the cervical score for the timing of human chorionic gonadotropin (hCG) administration in in vitro fertilization patients compared to the timing of hCG administration based upon estradiol and ultrasound measurements. Forty-two patients undergoing ovulation induction with human menopausal gonadotropin (hMG)/hCG for in vitro fertilization were studied. A total of 192 cervical scores was obtained together with plasma estradiol levels and pelvic sonography. hCG was given based on estradiol and ultrasound results without knowing the cervical score. An independent decision to give hCG was made based on the cervical score only following a mean of 2.5 days of a cervical score of 9-12 without the examiner's knowledge of estradiol and ultrasound results. This decision was theoretic and was not considered for the actual timing of hCG. In 16 (38%) of the cases this decision coincided with that based on estradiol and ultrasound. In 24 (57%) of the cases there was a 1-day gap. A direct correlation was found among the cervical score, the plasma estradiol concentration, and the mean diameter of the two leading follicles (P less than 0.001). The overall distribution of the cervical score grouped according to estradiol levels (less than 200, 201-400, and greater than 401 pg/ml) was significantly different (P less than 0.001). The proportion of "mature" cervical scores (score of 11-12) in the three different estradiol groups was 15.6, 34.5, and 68.0%, respectively. In conclusion, independent decisions to give hCG based on cervical score or estradiol and ultrasound were coincident +/- 1 day in 95% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100709 TI - Filterability of L-forms. AB - We investigated the recovery of L-forms through micropore filtration. The findings indicate that L-form recovery and viability are a function of filter size and preparation technique. Current methods in use for L-form isolation appear to give erroneously low results, underestimating the potential role of L forms in human disease. PMID- 3100708 TI - Evaluation of a mobile unit for indirect calorimetry during spontaneous ventilation. AB - The Mijnhardt Oxycon-4 (OX-4), designed for measurements of gas exchange during exercise using a mouth-piece, was adapted for use in recumbent patients by the introduction of a transparent canopy and a suction device. This system was evaluated in laboratory models and in patients. PMID- 3100711 TI - Prolonged secretion of prolactin in response to thyrotrophin-releasing hormone after hypothalamo-pituitary disconnection in the ewe. AB - Surgical disconnection of the ovine hypothalamus from the pituitary gland (hypothalamo-pituitary disconnection; HPD) has provided a useful experimental model for studying the control of gonadotrophin secretion. The objective of the present study was to define the characteristics of prolactin secretion using stimuli acting through the hypothalamus or directly on the pituitary gland in HPD ewes. Prolactin responses to either a stressful stimulus or the dopaminergic antagonists metoclopramide (20 mg i.v.) or chlorpromazine (50 mg i.v.) seen in intact animals (sham-HPD) were completely abolished by HPD. Injection of TRH (100 micrograms i.v.) caused an immediate release of prolactin in both groups of ewes. In the HPD ewes plasma prolactin concentrations remained raised for at least 3 h after TRH injection, whereas in sham-HPD ewes prolactin concentrations began to decline after 20 min. Administration of bromocriptine (1 mg i.v.) 10 min after TRH inhibited the prolonged response to TRH in HPD ewes. The results support the hypothesis that prolactin exerts a short-loop feedback effect on its own secretion at the hypothalamic level. PMID- 3100710 TI - Partial characterization of a mitomycin-C resistant T cell. AB - A cell resistant to concentrations of mitomycin-C associated with the inactivation of many in vitro immune responses is described. This cell is responsive to concanavalin A (Con A), poorly adherent to nylon wool, present in relatively greater numbers in lymph node than other lymphoid tissues, and is relatively radiosensitive. In part, the resistance of this T cell appears to relate to a reduced activity of a microsomal reductase responsible for converting mitomycin-C to its more active form. Discrepancies in reductase activity may represent a way to differentiate among subsets of lymphocytes. PMID- 3100712 TI - Characterization by high-performance liquid chromatography of circulating growth hormone-releasing factors in normal subjects. AB - Four forms of circulating immunoreactive human GH-releasing factor (ir-hGRF) have been identified in each of four normal subjects, with a mean increase in total ir hGRF of twofold over basal levels following a mixed meal. Plasma samples (200 ml) from each individual were subjected to large-scale Vycor extraction with initial purification by high-performance liquid chromatography on a reversed-phase C18 column, followed by analytical separation of the ir-hGRF components using a C3 wide-pore reversed-phase column, and subsequent radioimmunoassay of the fractions. The mean recovery of total ir-hGRF from the plasma (fasted and non fasted) was 76 +/- 16% (2 X S.E.M.). Analytical separation of the ir-hGRF revealed four components which co-eluted with synthetic hGRF-37, hGRF-40 and hGRF 44, and a peak eluting between hGRF-40 and -44 which may represent hGRF-42. The hGRF-40 was shown to be the predominant circulating molecular form in the fasted state in each subject, and in three out of four subjects following a mixed meal. The hGRF-44 showed the greatest percentage increase over basal in all four individuals. PMID- 3100713 TI - Gas exchange, storage and transport in voluntarily diving Xenopus laevis. AB - A closed, extracorporeal loop, containing oxygen and carbon dioxide electrodes, was developed in order to make continuous measurements of lung gas PO2 (PAO2) and PCO2 (PACO2) in undisturbed Xenopus laevis. Pulmonary R values (delta PACO2/delta PAO2) are about 0.8 during periods of lung ventilation in resting animals, but they fall very rapidly as a voluntary dive proceeds. In fact, the instantaneous R values for lung eventually fall to zero during a voluntary dive, since PAO2 continues to decline whilst PACO2 (after an initial increase) comes into a steady state as transcutaneous CO2 losses balance metabolic production. These relationships change during spontaneous underwater activity, aquatic hypercapnia or enforced diving, with significantly higher PACO2 levels being found at any PAO2 value than in resting animals. Emergence from such dives is marked by a considerable hyperventilation, leading to lung R values which are 2-3 times higher than those seen during lung ventilation of animals at rest. The lungs of Xenopus are therefore important in eliminating the CO2 stored during a period of breath-holding but not of major importance in forming part of that store themselves. The lungs of Xenopus are, however, important sources of stored oxygen during voluntary dives, the rate of use being clearly related to activity levels and dive durations. There could be sudden changes in the rate of PAO2 depletion during a dive, suggesting that factors additional to the metabolic rate of the cells may be important in determining the way in which the lung store is used. In a parallel series of experiments, O2 and CO2 partial pressures were determined in lung gas samples and in simultaneously drawn samples of blood from the femoral artery (systemic arterial) and left auricle (pulmonary venous) of animals making voluntary dives. These blood/gas data, together with results of previous experiments on Xenopus, have been used to develop an idealized model of O2 exchange, storage and transport during a 30-min voluntary dive. The volume of the O2 stores held in the lungs and various subdivisions of the circulation are shown in the model by plotting the PO2 of the store against its respective O2 capacitance. The model illustrates the overall importance of the lung as a source of oxygen during breath-holding and that early use of a large systemic venous O2 store may be an important basic function for cardiovascular adjustments seen in a dive. PMID- 3100714 TI - Blood gases and respiratory pattern in exercising fowl: comparison in normoxic and hypoxic conditions. AB - Clavicular air sac pressure, arterial blood gases and pH, and rectal temperature were measured in treadmill-exercised cockerels breathing air, 10% O2 in N2 or a mixture of 10% O2/3% CO2 in N2. Air sac pressures were used to estimate changes in the rate and the relative depth of breathing. In air-breathing conditions exercise took place at two intensities corresponding to treadmill speeds of 3.2 and 5.0 km h-1, respectively. Rectal temperature increased by 0.5 degrees C but there was no sign of thermal hyperventilation and arterial PCO2 remained constant. Increased ventilation was mainly brought about by changes in respiratory rate, with relatively small increases in depth. During exercise at 3.2 km h-1 inhalation of 10% O2 in N2 produced a 35% increase in ventilation and breathing became faster and shallower. Arterial PCO2 fell by 3-4 Torr, apparently as a result of lung hyperventilation. Addition of 3% CO2 to the hypoxic gas restored normal arterial PCO2 and reversed the trend to polypneic breathing. However, it failed to produce an exact matching of respiratory characteristics with those observed during isocapnic exercise hyperpnea. It is concluded that rapid, shallow breathing during hypocapnic hypoxia in running birds serves as a mechanism to minimize lung hyperventilation and CO2 washout. This reflex, which may stem from the intrapulmonary CO2 receptors, occurs in the face of a severe hypoxic challenge. Failure to match respiratory characteristics during isocapnic hypoxia and isocapnic exercise may be due to an inhibitory effect of the inhaled CO2 on these receptors. PMID- 3100715 TI - RecE-dependent lysogenic induction in the absence of repressor in Bacillus subtilis non-complementing diploids. AB - The RecE protein of Bacillus subtilis, known to be required for induction of the SOS response and of phi 105 prophage, was shown to be involved in mitomycin C induction of B. subtilis diploid lysogens carrying a silent phi 105 prophage in their unexpressed chromosome. These stable non-complementing diploid lysogens, formed by protoplast fusion and regeneration, did not synthesize repressor, so that the induction observed must have resulted from RecE-dependent activation of the prophage rather than from RecE-dependent inactivation of repressor. Mitomycin C treatment does not induce permanent expression of the silent chromosome, so the activation seems to be temporary, perhaps reflecting the action of an SOS function under RecE control. PMID- 3100716 TI - Effects of different methods of purification on aggregation of scrapie infectivity. AB - High levels of scrapie infectivity were found in detergent-insoluble residues of hamster brain purified by either repeated pelleting in 10% NaCl or by separation in Nycodenz gradients. Titres determined by the method of incubation interval assay were 100-fold higher than titres measured by endpoint dilution assay. The protein profiles and end-labelled RNA examined by one-dimensional polyacrylamide gel electrophoresis were not different from samples prepared from uninfected brain. Preparations produced by repeated pelleting were treated with RNase A and/or 7 M-urea with no loss of scrapie infectivity. However, the infectivity of samples prepared by gradient centrifugation in Nycodenz were reduced by 2 to 3 log10 LD50 by treatment with RNase A alone but not in combination with SDS. These results suggest that the scrapie agent may be aggregated by methods of purification employing pelleting in high concentrations of salt, or by adding polycations to disaggregated samples. PMID- 3100717 TI - Biological evidence that scrapie agent has an independent genome. AB - There are many distinct strains of scrapie agent, identified by their relative incubation periods and quantitative and qualitative neuropathological properties in inbred mice of particular genotypes. When serially passaged under specified conditions of mouse strain, route of infection and dose of infectivity these properties are stable. However, they may change in a predictable manner if the passage strategy is altered. The scrapie strain 87A shows what has previously been defined as Class III stability; it is stable when passaged at low dose in C57BL mice, but often suddenly changes its properties in the course of a single passage if high doses are used, always resulting in the same new strain. The latter, designated 7D, has shorter incubation periods and more extensive pathology than 87A, properties which are subsequently stable on serial passage even at high dose. This phenomenon has been seen repeatedly using scrapie isolates from six different natural cases in five different breeds of sheep. These isolates are closely similar in all their properties, showing them to be independent isolations of the 87A strain; there have been no isolations of 87A in which the phenomenon did not occur. On the other hand, none of the many other scrapie strains used in the same laboratory have shown this change. 87A brain samples consistently behave as if they contain 87A together with a smaller amount of 7D. This is so even after 87A has previously been passaged at high dilution, well beyond the limiting dilution for 7D, a procedure which would eliminate any minor agent strain originally present in the isolate. Therefore it is highly likely that the 7D in tissues of mice infected with 87A is generated de novo at each passage by mutational change from 87A during the incubation period. The established fact that many different strains exist and the considerable evidence that mutation can occur lead to the conclusion that scrapie agent has its own independently replicating genome. PMID- 3100718 TI - Inhibition of quisqualate-induced seizures by glutamic acid diethyl ester and anti-epileptic drugs. AB - Glutamic acid diethyl ester (GDEE) is a glutamate antagonist which acts preferentially at the quisqualate-sensitive receptor and has been shown to be an effective anticonvulsant in alcohol withdrawal and homocysteine-induced seizures but ineffective in other seizure models. To better characterize the role of the quisqualate-sensitive receptor in the generation of seizures, quisqualate was administered to mice by intracerebroventricular (ICV) route and immediate onset generalized seizures were observed. The anticonvulsant properties of GDEE and commonly used antiepileptic drugs (AEDs) were investigated with this seizure model. GDEE given by intraperitoneal blocked quisqualate-induced seizures dose dependently. Diphenyl-hydantoin (50 mg/kg IP), carbamazepine (50 mg/kg IP), diazepam (1; 4 mg/kg IP), phenobarbital (40; 80 mg/kg IP), and valproic acid (250; 340 mg/kg IP) were also administered prior to quisqualate-seizure induction. Only valproic acid blocked seizures at nonsedating doses. The GABA transaminase inhibitor aminooxyacetic acid (20 mg/kg IP) was ineffective, suggesting that here valproic acid is active at excitatory receptors rather than by potentiating GABA post-synaptic inhibition. These data are consistent with the hypothesis that the quisqualate-sensitive receptor is involved in some forms of clinically observed seizures, particularly those which are controlled by valproic acid. PMID- 3100719 TI - Gold-resistant bacteria: excretion of a cystine-rich protein by Pseudomonas cepacia induced by an antiarthritic drug. AB - P. cepacia bacteria adapted to growth in a chemically defined medium containing millimolar concentrations of Au(I) thiolates including the antiarthritic drug Au(I) thiomalate. The bacteria became very large, accumulated polyhydroxybutyrate and gold, and excreted a yellow protein ("thiorin"), which caused foaming of the culture medium. Thiorin was shown by 1H-NMR, amino acid analysis, and gel filtration chromatography to be of low molecular weight (ca. 9500) and to contain predominantly Cys (oxidized), Glx, and Gly. PMID- 3100720 TI - Hexacyanochromate ion as a paramagnetic anion probe for active sites of enzymes. AB - Hexacyanochromate ion, (Cr(CN)6)3-, was applied to ribonuclease T1 (RNase T1), which specifically cleaves RNA chains at guanylic acid residues. From kinetic studies, this anion was shown to bind to the active site of RNase T1 as a competitive inhibitor. Therefore, the line broadening effect of NMR resonances due to binding of (Cr(CN)6)3- was analyzed for the mapping of the active site of RNase T1. His-40 C2 proton resonance was significantly broadened, following His 92 C2 proton resonance upon binding of (Cr(CN)6)3-, while His-27 C2 proton resonance did not show any appreciable line broadening. Moreover, from the pH dependence of the line broadening effect, the binding of (Cr(CN)6)3- was shown to be controlled by the ionic state of Glu-58. Based on the present NMR results and x-ray crystal structure, the active site structure of RNase T1 is discussed. PMID- 3100722 TI - Distribution of alpha-(gamma-aminobutyryl)-hypusine. AB - The distribution of alpha-(gamma-aminobutyryl)-hypusine was examined in several organs of the rabbit and in the brain of the rat, rabbit, dog, ox, and monkey. The peptide occurred only in the brains, but appeared to be absent from dog brain. Concentrations were higher in the cerebral hemispheres than in other portions of the brain. No significant difference between white and gray matter was observed. PMID- 3100721 TI - Isolation and properties of the complex nonheme-iron-containing cytochrome b557 (bacterioferritin) from Pseudomonas aeruginosa. AB - A nonheme-iron-containing cytochrome b557, also known as bacterioferritin, was isolated from Pseudomonas aeruginosa. Gel electrophoresis showed that the protein subunits had a molecular weight of 18 kD and it is suggested that the intact molecule contained 24 subunits. The isolated protein contained 8.7% by weight Fe and 8% by weight phosphate. Most of the Fe was contained in the nonheme-iron core and could be readily removed by dialysis against 0.12 M thioglycollic acid. The resulting apobacterioferritin contained approximately one protoporphyrin IX group for every five subunits and, in addition, an unidentified fluorophor. The nonheme iron core was found to be amorphous with a mean core size of 60-65 A. PMID- 3100723 TI - Arachidonic acid oxidation by brain and placenta preparations from normal and placental insufficient fetal rabbit. AB - Cytosolic (100,000 g) fractions of fetal rabbit brain and placenta tissue convert [1-14C]arachidonic acid into several oxidation products identified with the lipoxygenase [12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE] and cyclooxygenase [prostaglandin E2 (PGE2)] pathways. Formation of 12-HETE and 15 HETE by fetal brain is time-dependent, reaching a plateau after 40 min and is linear with protein concentration. An apparent affinity constant of 0.06 mM and a Vmax of 0.1 mumol/h/g wet weight are presumably responsible for the excessive accumulation of 12-HETE and 15-HETE in comparison to PGE2 (Km = 0.5 mM). The latter is synthesized by the placenta particulate fraction but almost exclusively by the brain cytosol. Compared to brain, the activity of the placenta tissue is exceedingly higher and in addition to 12-HETE and 15-HETE there is a substantial formation of 12-L-hydroxyheptadecatrienic acid. Formation of 12-HETE and 15-HETE at 21 days is as effective as at 31 days gestation and is strongly inhibited by nordihydroguaiaretic acid (93%), BW755c (99%), and AA861 (84%) but not by indomethacin. Placenta and brain tissues of intrauterine growth retarded fetuses after ligation of placental blood vessels fail to convert arachidonic acid into other eicosanoids. Loss of enzymatic activity also observed in normal tissue after prolonged storage cannot be restored by the addition of several SH agents, ascorbate, or ferric iron. PMID- 3100724 TI - Phospholipid metabolism in mouse sciatic nerve in vivo. AB - To probe the activities of various pathways of lipid metabolism in peripheral nerve, six phospholipid-directed precursors were individually injected into the exposed sciatic nerves of adult mice, and their incorporation into phospholipids and proteins was studied over a 2-week period. Tritiated choline, inositol, ethanolamine, serine, and glycerol were mainly used in phospholipid synthesis; in contrast, methyl-labeled methionine was primarily incorporated into protein. Phosphatidylcholine was the main lipid formed from tritiated choline, glycerol, and methionine precursors. Phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol were the main lipids formed from serine, ethanolamine, and inositol, respectively. With time there was a shift in label among phospholipids, with higher proportions of choline appearing in sphingomyelin, glycerol in phosphatidylserine, ethanolamine in phosphatidylethanolamine (plasmalogen), and inositol in polyphosphoinositides, especially phosphatidylinositol 4,5 bisphosphate. We suggest that the delay in formation of these phospholipids, which are concentrated in peripheral nerve myelin, may, at least in part, be due to their formation at a site(s) distant from the sites where the bulk of Schwann cell lipids are made. We propose that separating the synthesis of these myelin destined lipids to near the Schwann cell's plasma membrane would facilitate their concentration in peripheral nerve myelin sheaths. At earlier labeling times, ethanolamine and glycerol were more actively incorporated into phosphatidylcholine and phosphatidylinositol, respectively, than later. The transient labeling of these phospholipids may reflect some unique role in peripheral nerve function. PMID- 3100725 TI - Phosphorylation and inactivation of brain glycogen synthase by a multifunctional calmodulin-dependent protein kinase. AB - Glycogen synthase was partially purified from canine brain to about 70% purity. The purified enzyme showed differences from the properties of the skeletal muscle enzyme with respect to molecular weights of the holoenzyme and subunit and phosphopeptide mapping. The multifunctional calmodulin-dependent protein kinase from the brain phosphorylated brain glycogen synthase with concomitant inactivation of the enzyme. Although about 1.3 mol of phosphate/mol subunit was maximally incorporated into glycogen synthase, 0.4 mol of phosphate/mol subunit was sufficient for the maximal inactivation of the enzyme. The results indicate that brain glycogen synthase is regulated in a calmodulin-dependent manner similarly to the skeletal muscle enzyme, but that the brain enzyme is different from the skeletal muscle enzyme. PMID- 3100726 TI - Delayed recovery of CO2 reactivity after one hour's complete ischaemia of cat brain. AB - The cerebrovascular CO2 reactivity was examined after 6 h, 1, 2, and 3 days and 1 year following 1 h complete brain ischaemia in the cat. After 6 h recirculation, the CO2 reactivity was completely suppressed although major EEG activity had recovered. After 2 days, CO2 reactivity began to reappear, but even after 1 year restitution was not complete. The prolonged (though partly reversible) attenuation of CO2 responsiveness suggests that ischaemia is followed by a long lasting state of haemodynamic imbalance, which may be responsible for the slow progress of post-ischaemic recovery processes. PMID- 3100727 TI - Phase II clinical trial of triazinate in combination with mitomycin C for patients with advanced gastric cancer. AB - Thirty-three patients with advanced measurable gastric cancer were treated with a combination of mitomycin C and triazinate. Twenty-nine of these patients had failed prior chemotherapy. Nine patients (27%) had an objective tumor response (median duration, 10 weeks). Median survival of all patients treated was 21 weeks. This study demonstrates that carefully selected patients with advanced gastric cancer who have failed a trial of chemotherapy, but are still ambulatory and maintaining adequate nutrition are appropriate subjects for studies of new treatment regimens. Based on the observed objective tumor response rate and median patient survival, further studies of these drugs in combination for the treatment of advanced gastric cancer are indicated. PMID- 3100729 TI - The effect of mediastinal irradiation on cardiac function of patients treated during childhood and adolescence for Hodgkin's disease. AB - To determine the frequency of cardiac dysfunction in patients treated during childhood or adolescence with mediastinal irradiation for Hodgkin's disease (HD), 28 patients underwent cardiac evaluation 19 to 182 months (median, 90 months) after the completion of radiation therapy. No patient had symptoms of cardiac disease. All were normotensive. All patients had a normal cardiothoracic ratio. There were no abnormalities of voltage or rhythm in the ECGs. The left ventricular end diastolic volume was increased in 19.2% of patients, none of whom had evidence of impaired left ventricular function. The left ventricular ejection fraction (LVEF) was increased in 15.3% of patients. No patient had a decreased LVEF. Pericardial thickening was demonstrated on echocardiograms from 12 of 28 patients (42.9%). Thickening was more frequent among those patients observed for 72 or more months (47.1%; eight of 17) than among those with shorter periods of follow-up (36.4%; four of 11). This study demonstrates that cardiac dysfunction is an infrequent sequela of mediastinal irradiation following treatment using an equally weighted, anterior-posterior technique. Longitudinal study of these patients will be necessary to determine the clinical significance and evolution of the occult pericardial thickening that was identified. PMID- 3100728 TI - Retroperitoneal fibrosis following treatment for Hodgkin's disease. AB - With improvement and refinement of therapy, the majority of Hodgkin's disease patients are alive and free of disease at 5 years. As these patients continue to be observed, a variety of late complications have been reported. We describe herein three patients who developed retroperitoneal fibrosis following definitive therapy for Hodgkin's disease. The incidence approaches that seen with methysergide. PMID- 3100730 TI - In vitro neuronal differentiation of Drosophila embryo cells. AB - Early gastrula-stage Drosophila embryo cells will differentiate in vitro to form several cell types, including neurons. We report here the morphological appearance of cultured embryo cells, the pattern of DNA synthesis, and the expression of neurotransmitter-metabolizing macromolecules. The cells initially exhibit no overt morphological differentiation, and all cells incorporate 3H thymidine following a 1 hr pulse-labeling period. As cells undergo morphological differentiation, fewer total cells as well as qualitatively different cell types incorporate label. By the time cells are 8 or 9 hr old, no myocytes or myotubes are labeled. In contrast, some neurons are labeled with a thymidine pulse as late as 18 hr. We have also stained cultured cells of various developmental ages with the insect neuron-specific antibody: anti-HRP. Some positive cells can be detected as early as 5 hr, when no overt morphological differentiation is apparent. As the cells differentiate, the staining is limited to the small, round neuronal type and its processes. These findings suggest that this neuron-specific cell marker is expressed very early in cultured gastrula-stage cells and may be used to identify neuronal precursor cells. We have studied the patterns of expression of several macromolecules involved in acetylcholine metabolism using these cultures. The appearance of choline acetyltransferase (ChAT), the biosynthetic enzyme for ACh production, is first detected in 5-hr-old cells. There is an initial phase of low-level expression, followed by a rapid rise in activity shortly after the differentiating neuron clusters make contact with one another. ChAT activity reaches a plateau in 36-48-hr-old cells. Acetylcholinesterase activity can be detected several hours before ChAT and also shows a period of low-level expression followed by a rapidly increasing phase, reaching a plateau at around 36-48 hr. 125I-alpha-bungarotoxin binding appears in cells about 4 hr old and rapidly approaches maximum levels by about 36 hr. The in vitro expression pattern for ChAT and AChE is similar to that seen in vivo. AChE activity has been localized histochemically to the neurons and their processes in vitro. The normal in vitro expression pattern for ChAT and AChE can be altered by adding various cholinergic drugs to the culture medium during cell differentiation. Medium conditioned by older cultures can also result in lower levels of ChAT and AChE expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100731 TI - Hyperosmotic blood-brain barrier disruption in brains of rats with an intracerebrally transplanted RG-C6 tumor. AB - To test the results of blood-brain barrier (BBB) disruption in the treatment of brain tumor, RG-C6 glioma was transplanted into the brains of rats. Intracarotid infusions of normal saline and hyperosmotic mannitol were then made, followed by intravenous injection of Evans blue dye plus albumin (EB, MW 68,000), horseradish peroxidase (HRP, MW 40,000), and 5-fluorouracil (5-FU, MW 130). Uptake of the drug and the consistency of drug levels in the normal brain and tumor varied widely among these three agents. Both EB and HRP penetrated the brain tumors but did not stain the normal brain tissues. After BBB opening, penetration of EB and HRP into the normal brain was drastically increased; however, the uptake of EB and HRP in the tumor was not increased. The concentration of 5-FU in the tumor was higher than that in the serum and, although it increased 1.5-fold after BBB opening, the increase was not statistically significant. Conversely, there was a progressive increase in concentrations of 5-FU in the tumor-free brain regions (p less than 0.05). These observations suggest that an intracarotid infusion of hyperosmotic mannitol may increase neurotoxicity because it allows greater delivery of anticancer drugs into the normal brain tissue than into the tumor tissues. PMID- 3100732 TI - Radiometric assay of bacterial growth: analysis of factors determining system performance and optimization of assay technique. AB - A quantitative technique for the measurement of 14CO2 released from a bacterial culture was evaluated. The technique uses liquid scintillation counting to record 14CO2 accumulation on a fluor-impregnated filter paper within a double-chambered scintillation vial that also houses the bacterial growth medium. We have successfully identified and corrected the major causes for a variably low detection efficiency, and also established the optimum mixture of reagents for the detection system. Incorporation of Triton X-100 into the scintillation fluid used for the detector reduced the variability between identical assays in a single batch from 50% to 5%, and, in conjunction with an increase in the scintillator concentration, raised the counting efficiency from 30% to 70-88%. The response of the improved detector is linear over a wide range of count-rates. Another significant modification was the interchange of growth and detector chambers. Overall, a 40-fold increase in count-rate during the exponential phase of bacterial growth was obtained by improving 14CO2 detection efficiency, increasing the rate of 14CO2 transfer from liquid to gas phases and enlarging the growth supporting capacity of the detector system. The minimum detection time for bacterial growth was shortened and the exponential phase of bacterial proliferation was lengthened by at least 2 hr. High counting efficiency, precision, and linearity make the improved detector a sensitive and reliable tool for radiometry of bacterial growth and metabolism. PMID- 3100733 TI - Effects of chelates and incubation media on platelet labeling with indium-111. AB - We studied the effects of various [111In]chelates and incubation media on labeling efficiency (LE) and in vivo survival of platelets. High LE of human and rabbit platelets in plasma were obtained with [111In]tropolone and [111In]mercaptopyridine-N-oxide. Indium-111 oxine in plasma resulted in a moderate LE and required a longer incubation time, while [111In]oxine sulfate had low LE and inconsistent labeling. High LE for all forms of [111In]chelates were achieved in labeling media free of plasma. However, in vivo platelet survival in rabbits was markedly reduced when platelets were labeled in the absence of plasma. PMID- 3100735 TI - Radiation absorbed dose from technetium-99m DTPA. AB - The whole-body retention of intravenously administered [99mTc]DTPA was measured by urine analysis and whole-body counting in eight normal subjects. On average, the elimination of [99mTc]DTPA was faster in these subjects than in 11 patients under study for hypertension whose whole-body retention data were used in MIRD Dose Estimate Report No. 12. The average residence time for [99mTc]DTPA in total body, less bladder contents, was only 65% of the MIRD value. However, despite this difference, the dosimetry is similar in both cases largely owing to the influence of radioactivity in bladder contents. Approximately 2-3% of the administered radioactivity was retained in the body for a time that was long relative to the physical half-life of 99mTc, and probably reflects a small amount of protein binding of the DTPA preparation. PMID- 3100734 TI - Radiation dose to upper airways from inhaled oxygen-15 carbon dioxide. AB - According to Powell et al., significant retention of 15O in the tracheal mucosa results in a radiation absorbed dose of 75 to 200 rad upon breathing of 15O-CO2 for one hour at 1 mCi/liter. Such a high dose would seriously compromise the 15O CO2 inhalation method for positron emission tomographic (PET) measurement of cerebral blood flow (CBF). In order to verify these results, we have assayed 15O activity in the tracheal region of three volunteers by PET during inhalation of 15O-CO2 and 15O-O2. Using methods similar to those of the above authors for estimating absorbed dose in the tracheal mucosa, we have obtained a value of 14 38 rad, which is more in keeping with 3-5 rad found by Bigler et al. from direct assay of mucus and saliva. We conclude that the 15O-CO2 inhalation method is a safe and practical means of measuring CBF by PET. PMID- 3100736 TI - Refining a classification system for fiscal and staffing management. AB - Believing that nurses must agree on a uniform system for defining nursing hours and on a method for determining costs, the author describes how an automated patient classification system was enhanced as a preliminary step to cost out nursing. Nursing administrators are encouraged to refine patient classification systems so that accurate data for fiscal and staffing management can be generated. PMID- 3100737 TI - Effects of a low carbohydrate isoenergetic diet on sleep behavior and pulmonary functions in healthy female adult humans. AB - To study the effects of a low carbohydrate, isoenergetic diet on pulmonary physiology and sleep behavior, we measured pulmonary functions and respiratory gas exchange and carried out ambulatory electroencephalographic studies after a week's intake of isoenergetic diet containing only 50 g carbohydrate per day in 6 healthy female adult humans in a free-living condition. Compared with their normal intake, during the week of low carbohydrate intake there was a rise in the level of fasting plasma 3-hydroxybutyrate from 0.12 +/- 0.07 (mean +/- SD) to 1.01 +/- 0.40 mmol/L(P less than 0.01, paired t-test); a fall in serum bicarbonate from 26.2 +/- 0.75 to 25.0 +/- 1.41 mmol/L (P less than 0.05) and in serum chloride from 107 +/- 1.3 to 105 +/- 1.8 mmol/L (P less than 0.05). Serum urea rose from 4.3 +/- 0.71 to 5.7 +/- 0.70 mmol/L (P less than 0.01), and serum uric acid from 0.34 +/- 0.08 to 0.39 +/- 0.10 mmol/L (P less than 0.05). Functional residual capacity was increased from 2.07 +/- 0.35 to 2.26 +/- 0.34 L (P less than 0.01). Respiratory gas exchange ratio fell from 0.81 +/- 0.05 to 0.75 +/- 0.04 (P less than 0.05) and partial pressure of expired carbon dioxide reduced from 22 +/- 3.3 to 21 +/- 3.1 mmHg (P less than 0.05). There was a reduction in endogenous carbon dioxide production and arterial carbon dioxide tension. An analysis of ambulatory electroencephalogram showed that REM latency increased from 66 +/- 8 to 111 +/- 38 min (P less than 0.05), with no significant changes in sleep time and stages. These studies show that a low carbohydrate isoenergetic diet is tolerable, influences sleep behavior, reduces carbon dioxide production and respiratory gas exchange ratio, and may be therapeutically useful in patients with hypercapnic respiratory failure. PMID- 3100738 TI - Effect of feeding peptic digest of soy protein isolate on rat serum cholesterol. AB - Growing rats were fed ad libitum soy protein isolate (SPI) or its peptic (SPI-P) or tryptic digest (SPI-T) for a month and their sera were examined for cholesterol and triglyceride levels and enzyme activities such as cholinesterase, glutamate-pyruvate transaminase (GPT) and alkaline phosphatase. The rats fed SPI P or SPI-T were inferior in growth to those fed SPI. Similarly, the serum glyceride level was lower in the SPI-P and SPI-T groups than in the SPI group. On the other hand, a significant difference was found in the serum cholesterol level between the SPI-P and SPI or SPI-T groups but not between the SPI and SPI-T groups. A similar tendency was observed for serum GPT and alkaline phosphatase activities, although there were no significant differences among dietary groups in small intestinal enzyme activities. As for the atherogenic index being a risk factor inducing atherosclerosis, the order of its value was SPI-P less than SPI less than SPI-T. PMID- 3100739 TI - Long-term mechanical ventilation in an acute care hospital: a positive approach. PMID- 3100740 TI - Pulpal responses to amalgam restorations in cavities with and without smear layer removal. AB - A conventional low copper amalgam was placed in cavities with and without smear layer removal and the amalgam restorations were covered with a resin overlay. The restored teeth were retrieved at 2, 28 and 56 days postoperatively in order to test for leakage and then pulpal reactions. More inflammation was seen in the teeth from which the smear layer had been removed. Abscesses were present in 6 teeth at 28 days but only one was associated with demonstrable bacteria. This study does not support smear layer removal before insertion of low copper amalgam restorations. PMID- 3100741 TI - Oral epithelial cell lipid synthesis in the presence of retinoic acid or nitrosonornicotine. AB - The current study examines the effects of N-nitrosonornicotine (NNN) and all trans-retinoic acid (RA) on the synthesis and composition of lipids of oral epithelial cells grown in culture. Cells were exposed to NNN, RA or methylene chloride (the vehicle for the NNN and RA) and the lipids labelled with [14C] acetate. Lipids were extracted from the cells, separated by paper chromatography, located by autoradiography, and acetate incorporation determined by liquid scintillation spectrometry. Cholesterol labelling was significantly decreased by the RA between 4 and 48 h when compared to the NNN-treated or control cells. After 48 h the incorporation levels in the presence of the two last compounds decreased. Free fatty acid labelling was also significantly less in cells exposed to RA, while labelling of triglycerides and phospholipids was increased. N nitrosonornicotine seemed to produce a decreased labelling of cholesterol after 96 h continuous exposure. The results of these studies suggest that retinoid rapidly elevates the cell content of lipid formed from the glycerolipid pathway and membrane mechanisms may be modulated by this effect. PMID- 3100742 TI - HLA-DR antigen detection in giant cell lesions. AB - Sixty-six giant cell lesions ranging from inflammatory to neoplastic were evaluated for HLA-DR antigens using formalin/paraffin tissue and a monoclonal antibody labelled by the avidin-biotin peroxidase. HLA-DR antigens were expressed in nearly all lesions, predominantly on round, macrophage-like cells. Granulomatous inflammatory lesions were generally more immunoreactive than non inflammatory lesions. Multinucleate giant cells were relatively unreactive in non inflammatory lesions as compared to inflammatory lesions. Determination of HLA-DR expression does not appear to be helpful in discriminating between the various giant cell lesions. PMID- 3100743 TI - Product identification of ameloblastomas: an immunohistochemical study. AB - Twenty-nine solid, plexiform and follicular ameloblastomas and control human developing teeth at different stages of maturation were formalin-fixed, paraffin embedded and sectioned for the study of laminin, fibronectin, and mannosyl, glucosyl, and galactosyl residues using the peroxidase antiperoxidase (PAP) and avidin-biotin peroxidase complex (ABC) staining methods, respectively. Monospecific antibodies to laminin and fibronectin and the affinity of the lectins for mannosyl, glucosyl, and galactosyl residues with RCA-I. Laminin is present during the stage of morphodifferentiation of normal tooth development within the basement membrane. Following cytodifferentiation and calcified matrix deposition, laminin is not detectable. Laminin is also found in the basement membrane of both follicular and plexiform ameloblastomas. In contrast, fibronectin is reactive only up to the stage of morphodifferentiation among the mesenchymal cells and at the epithelial-mesenchymal interface, and it becomes unreactive upon differentiation of odontoblasts and mesenchymal pulp tissue as well. Unlike laminin, fibronectin is unreactive in the basement membrane of plexiform follicular and ameloblastomas. PMID- 3100744 TI - Neurotropic melanoma of the lower lip. AB - The neurotropic melanoma is a rare and highly malignant variant of melanoma that possesses a biphasic neoplastic component. A lentigo maligna melanoma commonly precedes a downgrowth of spindle cells that exhibit fascicle formation and striking neurotropism. A strong predilection for occurrence on the lip has been indicated by published reports. Difficulties exist in the initial diagnosis of the tumor because of its biphasic growth pattern, while the biologic behavior of the tumor is that of multiple recurrences, perineural metastases with cranial neuropathies and intracranial disease, and regional and distant organ metastases. The clinical and histopathologic features of a neurotropic melanoma of the lip are shown, and a brief review of the histogenesis, treatment, and prognosis are presented. PMID- 3100745 TI - Evaluation of eugenol for mutagenicity by the mouse micronucleus test. AB - Mutagenicity of eugenol (2-methoxy-4-allylphenol) was evaluated by an in vivo eukaryotic assay in mice. A 50% lethal dose (LD50) for intraperitoneal (IP) delivery of eugenol was found to be 1109.6 mg/kg body weight (7.5% eugenol-in saline). Oral (PO) delivery via stainless-steel, esophageal cannulation was not lethal to 14,794 mg/kg body weight (100%) eugenol. Based upon recommended procedure, 80 and 25% LD50 doses were administered IP in 250 microliter volumes. Undiluted eugenol was administered PO in 100 microliter volumes. Delivery of eugenol by both regimes to male mice induced anaphase mutations in polychromatic erythrocytes as measured by the bone marrow micronucleus test. IP delivery of both doses induced the formation of micronuclei to significant levels (P less than 0.001) compared to saline controls. PO delivery of eugenol induced a much reduced frequency of micronuclei when compared to the IP route. However, a significant increase in micronuclei was evident when this test population was compared to its control group (P less than 0.003). These results suggest that eugenol presents some mutagenic capacity in eukaryotic hosts and should be evaluated for further toxicological effects. PMID- 3100746 TI - Granular cell reaction to surgical glove powder. AB - The histopathologic features characteristic of the inflammatory response associated with starch powder used as a lubricant for surgical gloves were investigated by implanting starch granules into 3 separate sites on the right side of 8 male Wistar rats. On the opposite side, a sham-operated site and sites implanted with talc were used as controls. Two rats were killed at 1, 2, 3 & 4 week intervals and tissue from the implanted sites was assessed for distinctive features. It was found that a consistent feature of the starch-implanted sites was the presence of large histiocytes containing prominent PAS-positive, diastase resistant inclusions. These cells were not found in the control sites and, thus, were considered characteristic of starch contamination in tissue, even in the absence of identifiable starch granules. A possible clinical case of reaction to starch, identified retrospectively, using these results is discussed. PMID- 3100747 TI - Crystalloids with calcareous deposition in the parotid gland: one of the possible causes of development of salivary calculi. AB - Aggregated crystalloids and calculi, up to 600 to 700 micron in diameter, found in the parotid gland tissue taken from a patient with chronic recurrent parotitis were examined histopathologically and microanalytically. In part of the periphery of calculi which had lamellated structure, layers of crystalloids in continuation with calculi were observed; and diffuse deposition of von Kossa-positive fine granules was seen in the innermost area of the crystalloid-layers. By electron probe x-ray microanalysis, phosphorus, sulphur and calcium were principally detected within the innermost area of the crystalloid-layers. The result of the present study lends support to the possibility that crystalloids have some relation to the development of salivary calculi in the human parotid gland. PMID- 3100748 TI - Expression of Class II transplantation antigens by epithelial cells in oral candidosis, oral lichen planus and gingivitis. AB - Biopsies from normal oral mucosa and oral mucosa affected by candidosis, lichen planus or gingivitis were compared with respect to the expression of two Class II transplantation antigens, HLA-DR and HLA-DQ, by epithelial cells and the relationship of these antigens to the distribution and frequency of T lymphocytes. Indirect immunohistochemistry with different mouse monoclonal antibodies was used on frozen and acetone-fixed sections. To evaluate the results, a score system based upon the expression of the Class II transplantation antigens by epithelial cells and the frequency of T-lymphocytes was used. In oral candidosis there was a marked expression of HLA-DR antigens throughout the epithelium. In addition, this type of epithelium was the only one that expressed HLA-DQ antigens. An intense intraepithelial infiltration of T-lymphocytes was observed. Oral lichen planus and gingivitis did, to a much lesser extent, cause the expression HLA-DR antigens by the epithelial cells. In both lesions, the number of T-lymphocytes within the epithelium did not exceed the number found in epithelium of normal mucosa. In these types of lesions, the subepithelial infiltrate varied in intensity but was mainly composed of T-lymphocytes reactive with anti-Leu 3a antibodies. The results of the present study imply that epithelial expression of the two different Class II antigens are related to the frequency of the T-lymphocytes and to the proximity of these cells to the epithelial cells. PMID- 3100749 TI - Interuniversity microscopic slide exchanges: a mechanism for peer review and continuing education in oral pathology. AB - One thousand seven hundred and three consecutive cases from a microscopic slide exchange with 10 institutions were evaluated for extent of agreement (or disagreement) defined as: A) complete agreement (85.8%). B) Disagreement- difference in diagnostic terminology, no significant pathologic or clinical implications (1.4%); C) disagreement--difference in diagnosis with pathologic significance only (7.7%); C1 disagreement--difference in diagnosis with pathologic significance only, radiographic interpretation necessary (1.1%); D) disagreement--major significance for prognosis and/or treatment (4.0%). Trends in disagreement were identified in the following tissue/location categories: mesenchymal lesions, minor salivary gland tumors, odontogenic tumors, fibro osseous lesions, and benign epithelial lesions. These are discussed in relation to the oral pathology literature. All disagreements with significance for prognosis and/or patient treatment were evaluated retrospectively in an attempt to resolve the disparities. The implications for peer review, continuing education, and teaching programs are addressed. PMID- 3100750 TI - Oral hairy leukoplakia: ultrastructural features. AB - Ten instances of a white plaque of the lateral tongue unique to homosexual males and referred to as oral hairy leukoplakia were analysed ultrastructurally. The surface epithelial layer exhibited extracellular, intracellular and intranuclear penetration by hyphae of Candida albicans, sometimes accompanied by coccobacilli in the extracellular space. The subcorneal epithelial layer included koilocytoid ballooned cells which had a paucity of cytoplasmic organelles and displayed condensation and emargination of the chromatin. Cells that exhibited these nuclear changes were found to be infected by a herpes-type virus which was visualized by electron microscopy in all ten cases. Clusters of nucleocapsids (86 110 nm in diameter) occurred in the nuclei and enveloped virions (111-175 nm in diameter) occurred in the cytoplasm and extracellular spaces. Virions showed budding from the nuclear envelope. Bundles of tubular structures (20 nm diameter) arranged in parallel occurred in the cytoplasm of some koilocytoid cells. There was no evidence by electron microscopy of the presence of papilloma virus within koilocytotic nuclei. PMID- 3100751 TI - Effect of diphosphonate on the prevention of X-radiation-induced inhibition of bone formation in rats. AB - A histologic and histometric study of the effect of EHDP (ethane-1-hydroxy-1,1 diphosphonate) on the alveolar wound healing of irradiated animals is presented. This drug was selected based on its osteosclerotic effect when applied at low doses. The three left mandibular molars of 80 male Wistar rats were extracted. The rats were grouped into 4 sets of 20 rats each. Group I received no further treatment; Group II received daily intraperitoneal injections of EHDP (7.5 mg/Kg of body weight during 10 days); Group III: 15 Gy of X-radiation were applied to the head; and Group IV were irradiated and injected with EHDP as were animals of Groups III and II. Half of the animals were killed after 14 days and the other half 30 days post-extraction. Sections were made at the level of the mesial socket of the first molar in a bucco-lingual orientation, on which histometric determinations of bone activity were made. The results showed the attenuation of the inhibitory effect of radiation on bone formation when the animals were treated with EHDP. PMID- 3100752 TI - Somatic gene therapy for human disease: background and prospects. Part II. PMID- 3100754 TI - Sanfilippo syndrome type D. PMID- 3100753 TI - Two cases of NADH-coenzyme Q reductase deficiency: relationship to MELAS syndrome. AB - Muscle biopsy specimens from two patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) were studied biochemically. 14CO2 production rates from (1-14C)pyruvate, (U-14C)malate, and (1 14C)2-ketoglutarate were all decreased in intact mitochondria in both patients. Rotenone-sensitive NADH cytochrome c reductase activities were decreased to 8% (patient 1) and 6% (patient 2) of control values; succinate cytochrome c reductase and cytochrome c oxidase values were within normal limits. These results indicate that both patients have a defect of NADH-CoQ reductase of the respiratory chain and that MELAS can be brought about by a defect of NADH-CoQ reductase. PMID- 3100755 TI - Microflora of the urethra in adolescent boys: relationships to sexual activity and nongonococcal urethritis. AB - Urethral cultures were obtained from 90 adolescent youth, 16 of whom denied previous sexual activity. Among the sexually active boys was a group of 32 with clinically significant pyuria, consistent with the diagnosis of urethritis, on a first-part urinalysis (FPU) specimen. To relate differences in urethral microflora to sexual activity, 42 sexually active patients with a negative FPU were compared with the never sexually active group. The profile of anaerobic, but not aerobic, bacteria isolated from the urethra was related to the presence or absence of previous sexual activity. Mycoplasma species and Ureaplasma urealyticum were isolated from sexually active patients only, and may be markers of sexual activity in adolescent boys. Of the 32 patients with FPU evidence of urethritis, 22 (69%) had cultures positive for Chlamydia trachomatis, and an additional three (9%) had cultures positive for Neisseria gonorrhoeae. The findings in sexually active patients with a positive FPU were otherwise similar to those of sexually active patients without evidence of urethritis. C. trachomatis appears to be the most important agent of urethritis among adolescent boys with a positive FPU. PMID- 3100757 TI - In vitro excystation and structure of Sarcocystis suicanis Erber, 1977, sporocysts. AB - Methods previously described for artificially excysting coccidia were applied to oocysts and sporocysts of Sarcocystis suicanis recovered from the intestinal mucosa of experimentally infected dogs. Observations with a scanning electron microscope showed that sporocysts consisted of 4 plates, each with a series of accessory veinations; plate margins joined at obtuse angles; plates separated at their margins and curled inward, allowing the sporozoites to escape. Transmission electron microscopy suggested that the sporocyst wall is ultrastructurally similar to that of other coccidia. PMID- 3100756 TI - In vitro cultivation of meronts of Sarcocystis cruzi. AB - Several established cell lines were tested for their ability to support in vitro development of meronts of Sarcocystis cruzi. Sporozoites penetrated bovine monocytes (BM), bovine pulmonary artery endothelial cells (CPA), Madin-Darby bovine kidney cells and mouse macrophages, but developed to meronts in BM and CPA only. Sporozoites developed to large meronts that contained approximately 180-350 merozoites, whereas merozoites formed small meronts with 50-100 merozoites. Mature large meronts were present at 18-86 days after inoculation (DAI) in BM and at 16-72 DAI in CPA. Small meronts were present at 23-115 and 23-91 DAI in BM and CPA. Considerably more merozoites developed in CPA than in BM. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that merozoites harvested at 36 and 48 DAI each had 1 unique protein as well as numerous common proteins. PMID- 3100758 TI - The fecundity of Schistosoma mansoni in chronic nonhuman primate infections and after transplantation into naive hosts. AB - Adult Schistosoma mansoni worms were transplanted from 8 nonhuman primates with chronic infections into 8 naive recipients, in an effort to test the hypothesis that worm fecundity reduction in chronic infections is the result of host immunity or some other host effect. Techniques for perfusing living donors without the added use of anti-schistosomal drugs and for reducing the likelihood of post-operative bacterial endotoxemia and septic shock are described. Fecundity values in terms of eggs per day per female worm were obtained for the worms in their original and in their new hosts and compared. In 3 experiments, perfusions were incomplete and the donors were saved, enabling direct comparisons of fecundity to be made in subpopulations of worms in both their original and new hosts, after equal life spans. In only 1 of the 8 transplantations was there a clear increase in fecundity after surgical introduction into a naive host. Therefore, these experiments fail to support the hypothesis that reduced fecundity of S. mansoni worms in permissive nonhuman primate hosts is a reversible result of host immunity or some other host-derived factor. Despite this negation, further evidence for reduced worm fecundity in older infections was obtained. In the absence of in vivo evidence for immune-mediated antifecundity, worm senescence is the most likely explanation for this finding, with irreversible immune damage to the worms being a less attractive alternative hypothesis. PMID- 3100759 TI - Fallisia parasites (Haemosporidia: Plasmodiidae) from the flying lizard, Draco maculatus (Agamidae) in Thailand. AB - Plasmodium (Fallisia) siamense n. sp. was described from the flying lizard Draco maculatus (Agamidae) collected near Bangkok, Thailand. Parasitic in thrombocytes, it produces 18-64 merozoites in schizonts that are larger than the usually oval gametocytes. Both gametocyte sexes showed a prominent nucleus, elongate in macrogametocytes and triangular in microgametocytes. This is the first Fallisia parasite described from a host outside the Neotropical Region, although presence of the genus in Australasia was reported 40 years ago, without formal taxonomic designation. PMID- 3100760 TI - Studies of the life cycle of Pterygodermatites nycticebi (Monnig, 1920) Quentin, 1969. PMID- 3100761 TI - Treatment of trypanosome-infected mice with exogenous interferon, interferon inducers, or antibody to interferon. PMID- 3100762 TI - Ossification of the Achilles tendon. PMID- 3100763 TI - Effects of adenosine on sympathetic vasoconstriction in dog gracilis muscle. AB - The effects of intra-arterial infusions of adenosine (ADO) on sympathetic vasconstrictor responses were studied in the gracilis nerve-muscle preparation of the dog under constant flow conditions. Sympathetic nerves to the muscle were activated at a frequency of 1 Hz for 2 min during infusions of ADO, 2 chloroadenosine, nitroglycerine or hydralazine. ADO concentrations of 1, 10 and 50 microM decreased perfusion pressure by 19, 42 and 57 mm Hg, respectively, from a control (saline infusion) perfusion pressure of 110 mm Hg. Sympathetic vasoconstrictor responses were attenuated only at 50 microM ADO. Sympathetic responses during 1 and 10 microM ADO infusion were the same as during infusion of 10 and 100 microM nitroglycerine, which produced the same degree of vasodilation as 1 and 10 microM ADO, respectively. Except for greater vasodilator potency, 2 chloroadenosine infusions produced effects similar to ADO. Infusion of hydralize produced concentration-dependent decreases in control perfusion pressure and sympathetic vasoconstrictor responses. These results indicate that intra-arterial administration of ADO or one of its stable analogs (2-chloroadenosine) does not cause inhibition of sympathetic vasoconstrictor responses except at concentrations that cause nearly maximal vasodilation. PMID- 3100764 TI - Chronic effects of an alpha-glucosidase inhibitor (Bay o 1248) on intestinal disaccharidase activity in normal and diabetic mice. AB - Bay o 1248 is a potent alpha-glycosidase inhibitor that reduces postprandial hyperglycemia when administered p.o. with sucrose or maltose. The compound binds to and competitively inhibits the alpha-disaccharidases and is also readily absorbed across the intestinal mucosa. To evaluate its effect on the activity of disaccharidases and on metabolic control, groups of obese diabetic mice (C57BLKsJ db/db) were given the drug for periods of 3, 7 and 84 days as a drug food mixture (5 or 10 mg/100 g of food). Nondiabetic mice of the same strain were dosed for 3 and 7 days. The drug did not influence body growth, food intake or fasting blood glucose. However, urine glucose excretion was significantly decreased at the higher dose in the diabetic mice. The drug had no effect on the protein content of jejunum (proximal and middle thirds) or ileum (distal third) of the small intestine. The activity of sucrase and maltase was significantly decreased in practically all segments of the small intestine in both diabetic and nondiabetic mice. These changes were evident after 3 days of drug administration. Lactase was not affected by the drug. The mechanism underlying these changes, although unclear, is of significant interest and deserves further investigation. PMID- 3100765 TI - Decreased fentanyl and alfentanil dose requirements with age. A simultaneous pharmacokinetic and pharmacodynamic evaluation. AB - The effect of increasing age on the dose of fentanyl or alfentanil required to produce the same electroencephalographic (EEG) stage was studied in adult male patients. The pharmacokinetic and pharmacodynamic components of each patient's dose-response relationship were evaluated simultaneously. Frequent arterial blood samples drawn during and after an infusion of fentanyl or alfentanil were assayed by radioimmunoassay and permitted determination of each patient's pharmacokinetic profile. The EEG was analyzed by power spectral analysis and a parameter (spectral edge frequency) chosen to quantitate the narcotic-induced EEG slowing. An inhibitory sigmoid Emax pharmacodynamic model related spectral edge frequency to narcotic serum concentrations. The dose requirement of fentanyl or alfentanil decreased significantly with increasing age (a 50% decrease from age 20 to 89). No age-related changes in the pharmacokinetic parameters were found. Brain sensitivity (as determined by EEG changes) did decrease significantly with age. Thus, the decreased dose requirement in the elderly had a pharmacodynamic explanation, using the EEG as a measure of narcotic drug effect. PMID- 3100766 TI - Mode of vasorelaxing action of 5-[3-[[2-(3,4-dimethoxyphenyl)-ethyl]amino]-1 oxopropyl]-2,3,4,5- tetrahydro-1,5-benzothiazepine fumarate (KT-362), a new intracellular calcium antagonist. AB - In rabbit aorta, pretreatment with KT-362 (KT; 10(-6) and 10(-5) M) inhibited contractile responses to norepinephrine (NE; 3 X 10(-9)-10(-5) M) and methoxamine (10(-7)-10(-4) M) but failed to affect responses to potassium (10-70 mM). KT (10( 5) M) partially inhibited Ca++-induced contractions in K+-depolarized aorta pre equilibrated in a Ca++-free medium. After incubation of tissues for 30 min in a Ca++-free medium containing EGTA (0.2 mM), residual responses to NE and methoxamine were inhibited by KT (10(-6)-10(-4) M) and nitroglycerin (10(-5) M), but not by nifedipine, verapamil or diltiazem (all 10(-5) M). The inhibitory action of a combined treatment with KT and nitroglycerin (both 10(-5) M) on the residual response to NE was also much greater than that of either agent alone. In a Ca++-free medium, the residual caffeine-induced contraction of rabbit iliac artery was inhibited by KT (10(-5)-10(-4) M) but not by nifedipine (10(-5) M). The inhibitory action of KT on the residual responses to methoxamine and caffeine in a Ca+-free medium was much greater than that of nitroglycerin. In a Ca++-free medium with low EGTA (0.01 mM), D600 (10(-5) M) and NE (3 X 10(-7) M), the addition of Ca++ (2 mM) resulted in a tonic contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100768 TI - Inhibitory effects of amphetamine on potassium-stimulated release of [3H]dopamine from striatal slices and synaptosomes. AB - Amphetamine, 10(-7) M or greater, evoked the release of [3H]dopamine ([3H]DA) and inhibited subsequent K+-evoked [3H]DA release from striatal synaptosomes superfused at a flow rate (1 ml/min) that prevented reuptake. Amphetamine inhibited the K+-evoked release of [3H]DA to a lesser extent in striatal slices or in synaptosomes superfused at a flow rate (0.35 ml/min) that allowed reuptake. The observed decrease in amphetamine inhibition of K+-evoked release was primarily due to amphetamine blocking [3H]DA reuptake. Interneuronal interactions may account for some of the inhibitory effects of amphetamine on K+-evoked release in the slice. Inhibition of K+-evoked release from either slices or synaptosomes was still evident when 10(-6) M amphetamine was removed from the superfusion buffer and the spontaneous release had returned to control levels. The presence of Ca++ during amphetamine exposure was required for subsequent inhibition of K+-evoked release in synaptosomes. Amphetamine in the presence of Ca++ did not affect the subsequent release of [3H]DA evoked by the Ca++ ionophore, A23187. Therefore, amphetamine inhibition of the K+-evoked release of [3H]DA cannot be explained by prior depletion of Ca++-releasable pools. Nifedipine, 1 microM, failed to block either the Ca++-dependent release of [3H]DA or the inhibition of K+-evoked release by amphetamine. However, 1 mM cobalt inhibited the Ca++-dependent release of [3H]DA by amphetamine and antagonized the inhibition of K+-evoked release after amphetamine exposure. This suggests that amphetamine may open voltage-dependent Ca++ channels sensitive to cobalt but not nifedipine. Amphetamine may desensitize these voltage-dependent Ca++ channels and inhibit their activation by K+ depolarization. PMID- 3100769 TI - In vitro evidence of an endothelial cell-dependent antiplatelet activity for isosorbide dinitrate, but not for its 2- and 5-mononitrate metabolites. AB - In an experimental model in which cultured endothelial cells (EC) and platelets were incubated with autologous plasma, we investigated the pharmacological modulations by isosorbide nitrates (ISN) [isosorbide dinitrate (ISDN) + 2 isosorbide mononitrate (2-ISMN) + 5-ISMN] of the EC-induced inhibition of platelet aggregation; and the associated changes in prostanoid profile of these mixed EC-platelet suspensions. ISDN antiplatelet activities were found to be magnified profoundly by EC, being dependent upon both ISDN concentration and EC number, e.g., 5.10(-5) M ISDN in the presence of 2.10(4) cells, fully arrested ADP-induced aggregation, whereas the same ISDN concentration induced 30% inhibition in control platelet activities. In contrast, there were no significant changes in 2- and 5-ISMN antiaggregating properties, whether incubated in the presence or absence of EC. Thromboxane B2 accumulated noticeably after aggregation, whereas 6-keto-prostaglandin (PG) F1 alpha and PGE2 accumulated poorly in the medium. In the presence of EC, thromboxane B2 accumulation fell in parallel to the extent of aggregation, whereas 6-keto-PGF2 alpha and PGE2 accumulated in the medium. Aspirin-treated, washed ECs still inhibited platelet aggregation. ISDN was the only ISN capable of inducing PG-accumulation profile changes. These results demonstrate the existence of an endothelium-dependent ISDN antiplatelet activity. Furthermore, this effect is specific to ISDN not being shown by its mononitrate metabolites. These results suggest that PG accumulation changes may be a consequence rather than a cause of the inhibition of platelet activity by (ISDN-stimulated) EC. PMID- 3100770 TI - SR 95191, a selective inhibitor of type A monoamine oxidase with dopaminergic properties. I. Psychopharmacological profile in rodents. AB - SR 95191 [3-(2-morpholino-ethyl-amino)-4-cyano-6-phenyl-pyridazine], a novel compound, has been shown in preliminary experiments to inhibit type A monoamine oxidase (MAO). This report describes the activities of SR 95191 in behavioral experiments in mice and rats and shows that SR 95191 has the profile of a selective type A MAO inhibitor (MAOI). Moreover, SR 95191 also possesses dopamine (DA) stimulant properties. The activities of SR 95191 were compared to those of the MAOIs moclobemide, clorgyline, pargyline and l-deprenyl, as well as to those of the antidepressant drugs imipramine, nomifensine and indalpine and to those of the DAergic drugs (+)-amphetamine and apomorphine. SR 95191 p.o. antagonized the effects of reserpine in mice and rats, decreased immobility in the mouse despair test, antagonized haloperidol-induced catalepsy in rats and potentiated 5 hydroxytryptophan in mice and rats with an overall potency which was half that of imipramine. SR 95191, like moclobemide, did not potentiate yohimbine-induced lethality and did not antagonize oxotremorine-induced tremor. Like selective type A MAOIs, SR 95191 potentiated 5-hydroxytryptophan-induced tremor without affecting beta-phenethylamine-induced stereotypies in mice. SR 95191 did not antagonize 3-hydroxy-4-methyl-alpha-phenylethylamine-induced hyperthermia. Like all DA stimulant drugs, SR 95191 induced stereotypies in rats, which were blocked by haloperidol and alpha-methylparatyrosine, and induced contralateral turning in mice with a unilateral striatal 6-hydroxydopamine lesion. Based on these results, it is postulated that SR 95191 has a unique profile of activity combining the properties of a selective type A MAO inhibitor and those of an atypical DAergic drug. PMID- 3100767 TI - 6-hydroxydopamine treatments enhance behavioral responses to intracerebral microinjection of D1- and D2-dopamine agonists into nucleus accumbens and striatum without changing dopamine antagonist binding. AB - Behavioral responses to D1 and D2-dopamine agonists are enhanced when these agonists are administered systemically to 6-hydroxydopamine (6-OHDA)-lesioned rats. In the present investigation, microinjection of SKF-38393, a D1-dopamine agonist, into the nucleus accumbens of adult rats lesioned as neonates with 6 OHDA produced a dose-related increase in locomotor activity that was enhanced markedly compared to control. LY-171555, a D2-agonist, elicited less locomotor activity than did SKF-38393 after microinjection into this site. Administration of SKF-38393 or LY-171555 into the nucleus accumbens did not increase locomotion in unlesioned rats at the doses administered to lesioned animals. In adult-6-OHDA lesioned rats, microinjection of SKF-38393 into the nucleus accumbens also increased locomotion more than did LY-171555. As described previously, systemic administration of SKF-38393 produced little locomotion in adult-6-OHDA-lesioned rats, whereas LY-171555 produced a markedly enhanced response. Administration of SKF-38393 or LY-171555 into the caudate nucleus of neonatally and adult-6-OHDA lesioned rats produced negligible locomotor activity, but did induce stereotypic behaviors similar to those observed after systemic treatment with these drugs. Stereotypic behaviors occurred to a greater degree in the 6-OHDA-lesioned rats than in unlesioned controls. A regional specificity for certain behaviors induced by dopamine agonist administration was observed. In spite of the enhanced behavioral responses of D1 and D2-dopamine agonists after microinjection into the brain of 6-OHDA-lesioned rats, binding of [3H]spiperone (D2-receptor antagonist ligand) and [3H]SCH 23390 (D1-receptor antagonist ligand) to tissue from striatum and nucleus accumbens was not altered significantly. In contrast to this lack of change in binding characteristics in 6-OHDA-lesioned rats, blockade of dopaminergic transmission with haloperidol treatment caused an elevation of [3H]spiperone binding sites in striatum without affecting affinity for the site. However, chronic haloperidol treatment did not alter significantly [3H]SCH 23390 binding to striatal membranes. These latter findings suggest that chronic dopamine receptor blockade need not produce the same adaptive mechanisms as destruction of dopamine-containing neurons. Thus, a change in receptor characteristics as measured by dopamine antagonist binding does not account for the behavioral supersensitivity observed after D1- and D2-dopamine agonist administration to neonatally or adult-6-OHDA-treated rats. PMID- 3100771 TI - SR 95191, a selective inhibitor of type A monoamine oxidase with dopaminergic properties. II. Biochemical characterization of monoamine oxidase inhibition. AB - SR 95191 [3-(2-morpholino-ethyl-amino)-4-cyano-6-phenylpyridazine] is a novel psychotropic drug which possesses the pharmacological properties of a selective, reversible type A monoamine oxidase inhibitor (MAOI). The MAOI activity of SR 95191 was examined in the rat brain, liver and duodenum and compared to that of clorgyline, harmaline, l-deprenyl, moclobemide and cimoxatone. In vitro, SR 95191 selectively inhibited MAO-A and was less potent than cimoxatone, clorgyline and harmaline, but was more potent than moclobemide. Ex vivo, SR 95191 also preferentially inhibited MAO-A in the brain and was 6 and 13 times less potent than cimoxatone and moclobemide, respectively. Like all MAO-A inhibitors, SR 95191 in vivo caused a dose-dependent increase in striatal 3-methoxytyramine, dopamine, serotonin and in hypothalamic norepinephrine contents. A concomitant decrease in deaminated metabolites was observed. SR 95191 inhibited peripheral MAO activity in liver and duodenum. In brain, liver and duodenum, MAO inhibition induced by SR 95191 was short-lasting. Repeated dosing for 14 days did not enhance MAO-A inhibition. Like all reversible MAOIs, SR 95191 antagonized the long-lasting MAO-A inhibition induced by clorgyline. Finally, SR 95191 did not affect monoamine uptake either in vitro or in vivo and did not interact in vitro with a variety of neurotransmitter or drug receptor sites. Based on these results it is postulated that SR 95191 is a selective and reversible type A MAOI of medium potency, which may be of therapeutic benefit in depressed patients. PMID- 3100772 TI - Acute and chronic effects of ethanol and its metabolites on vascular production of prostacyclin in rats. AB - The cutaneous vasodilation produced by ethanol is exaggerated when acetaldehyde levels are increased after aldehyde dehydrogenase inhibition, producing a flushing reaction, the mechanism of which is unknown. The authors investigated whether ethanol and its metabolites affect the vascular release of prostacyclin, a potent vasodilator, and whether such an effect might be modified by chronic alcohol consumption. Aortic rings from rats fed Chow ad libitum or pair-fed liquid diets containing either ethanol (36% of energy) or isocaloric carbohydrate for 4 to 5 weeks were incubated in Krebs-Ringer bicarbonate supplemented with saturating amounts of arachidonate (10-20 microM) in the presence of ethanol (10 100 mM), acetaldehyde (10-100 microM) or acetate (1.25-5 mM). Prostacyclin was measured by the radioimmunoassay of 6-keto-prostaglandin F1 alpha. Acetaldehyde produced a concentration-dependent stimulation of prostacyclin production both in alcohol-fed and control rats, whereas acetate did not. This effect was associated with increased conversion of arachidonate (either exogenous or released with A23187) and of prostaglandin endoperoxide H2 to prostacyclin. Ethanol did not affect prostacyclin release in control rats, but, in aortas from alcohol-fed animals, 50 mM ethanol did stimulate prostacyclin formation. These effects may contribute to the cardiovascular responses associated with high blood acetaldehyde levels in flushers and with high ethanol levels in alcoholics. In conclusion, acetaldehyde is a potent stimulant of vascular prostacyclin production. This effect is due, at least in part, to enhanced activity of prostacyclin synthase. Ethanol acquires such a stimulatory effect on prostacyclin formation after chronic alcohol consumption. PMID- 3100773 TI - Dissociation of myosin phosphorylation and active tension during muscarinic stimulation of tracheal smooth muscle. AB - The Ca dependence of contraction and myosin phosphorylation was investigated in canine tracheal smooth muscle stimulated with carbachol, K or serotonin. Previous studies of tracheal muscle showed carbachol concentration-response curves for contraction and myosin phosphorylation were superposable. In contrast, there was a striking difference in the Ca++ sensitivities of tension and myosin phosphorylation when Ca++ concentration-response curves were constructed in the presence of 10(-7) M carbachol. Significant phosphorylation (greater than 0.3 moles phosphate/mole 20,000 dalton myosin light chain) was observed in the absence of active tension. In the present study, carbachol (10(-7) and 10(-6) M) and serotonin (10(-5) M) also induced significant myosin phosphorylation in low Ca++ solutions (0-0.025 mM CaCl2) without proportional increases in tension. K+ depolarization in Ca++-free physiological salt solution (60 mM KCl, 10(-6) M atropine) yielded phosphorylation not significantly different from basal levels. All stimulants induced active stress after readmission of Ca. The Ca++ dependence curve for myosin phosphorylation in muscles stimulated with carbachol was shifted up and to the left of the force curve. Atropine (10(-6) M) significantly reduced phosphorylation induced by carbachol in Ca++-free solutions, as did 3 X 10(-6) M nifedipine and 10 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. Phorbol 12-myristate, 13-acetate or phorbol 12,13-dibutyrate did not increase basal phosphorylation or phosphorylation in low Ca++ solutions, suggesting that protein kinase C did not phosphorylate myosin in this case. Myosin phosphorylation under these conditions is not sufficient to support contraction, and is reduced by treatments that decrease Ca++ entry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100774 TI - Behavioral effects of the pyrazoloquinoline CGS 9896: agonist and antagonist actions in squirrel monkeys. AB - The behavioral effects of 2-p-chlorophenylpyrazolo[4,3-c]quinolin-3(5H)-one (CGS 9896) were compared with those of lorazepam and zopiclone in squirrel monkeys. Two groups of monkeys were trained to respond under a fixed-interval schedule of food presentation. In one group, responding was suppressed (punished) by superimposing a fixed-ratio schedule of response-produced shock. Dose-effect curves were determined for all three drugs by administering cumulative doses i.v. during timeout periods that preceded sequential components of the fixed-interval schedule. Low and intermediate doses of CGS 9896 (0.03-3.0 mg/kg), lorazepam (0.03-0.3 mg/kg) or zopiclone (0.1-1.0 mg/kg) produced dose-related increases in the rates of both suppressed and nonsuppressed responding. The maximal increases in response rates produced by CGS 9896 were usually less than those produced by either lorazepam or zopiclone. Pretreatment with the benzodiazepine antagonist Ro 15-1788 antagonized the increases in suppressed and nonsuppressed response rates produced normally by intermediate doses of CGS 9896, lorazepam or zopiclone, suggesting that the rate-increasing effects of the three drugs are mediated similarly. CGS 9896 was studied additionally for antagonist activity by administering selected doses before lorazepam or zopiclone. Pretreatment with a high dose of CGS 9896 (5.0 mg/kg) antagonized the rate-increasing effects of both lorazepam and zopiclone, suggesting that CGS 9896 has antagonist effects in addition to its agonist effects at benzodiazepine recognition sites. PMID- 3100775 TI - Comparison of the effects of two 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs, 1-methyl-4-(2-thienyl)-1,2,3,6-tetrahydropyridine and 1-methyl-4-(3 thienyl)-1,2,3,6-tetrahydropyridine, on monoamine oxidase in vitro and on dopamine in mouse brain. AB - 1-Methyl-4-(2-thienyl)-1,2,3,6-tetrahydropyridine (2-MTTP) and 1-methyl-4-(3 thienyl)-1,2,3,6-tetrahydropyridine were compared with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) with respect to their interactions with MAO (monoamine oxidase) in vitro and their ability to produce persistent depletion of striatal dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in mice. Both 2-MTTP and 1-methyl-4-(3-thienyl)-1,2,3,6-tetrahydropyridine were like MPTP in being potent, competitive inhibitors of MAO-A (MAO type A) and weak, noncompetitive inhibitors of MAO-B (MAO type B) in vitro. 2-MTTP resulted in persistent depletion of striatal dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid 1 week after the last of four daily injections to mice although 2-MTTP was less than one-fourth as potent as MPTP. The other isomer, 1-methyl-4 (3-thienyl)-1,2,3,6-tetrahydropyridine, failed to deplete dopamine or its metabolites in mouse striatum. Dopamine and its metabolites were also depleted in mouse nucleus accumbens by 2-MTTP and by MPTP; however, norepinephrine in frontal cortex was depleted by MPTP but not by 2-MTTP. The depletion of dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid by 2-MTTP was prevented by pretreatment with deprenyl, a selective inhibitor of MAO-B, or with EXP 561, a dopamine uptake inhibitor, just as the depletion by MPTP was prevented. Mouse brain MAO oxidized 2-MTTP in vitro less rapidly than it oxidized MPTP; deprenyl was a potent inhibitor of the oxidation of both substrates, suggesting that MAO-B oxidizes both 2-MTTP and MPTP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100776 TI - Effects of 6-hydroxydopamine on hemodynamic function in the pithed rat. AB - The effects of 6-hydroxydopamine (6-HDA) on hemodynamic function were assessed in pithed male Sprague-Dawley rats prepared for continuous measurement of cardiac output by electromagnetic flowmetry. One week after 6-HDA administration, 100 mg/kg s.c., blood pressure increments elicited by electrical stimulation of the lumbar sympathetic outflow (0.25-8.0 Hz) were reduced significantly (P less than .01), whereas heart rate responses were normal. The reduction in blood pressure responses was due to an attenuation of increases in both cardiac output (P less than .01) and total peripheral resistance (P less than .02). Cardiac output responses were reduced exclusively due to a fall in stroke volume inasmuch as heart rate increases were not altered by 6-HDA. Furthermore, the reduction in neurally mediated cardiac output increases by 6-HDA appeared to result from impaired sympathetic control of inotropic activity. This conclusion was supported by the observation that pretreatment with the beta adrenergic receptor antagonist, nadolol, markedly decreased cardiac output responses in control animals, but did not further attenuate cardiac output increases in 6-HDA-treated rats. However, after nadolol a substantial cardiac output response remained that was equivalent in 6-HDA-treated and control rats. This remaining response may be accounted for by venous constriction and because there was no difference in the cardiac output increases in the two groups after nadolol it appears that neural control of venoconstriction was not impaired by 6-HDA. Thus results of the present study indicate that at 1 week after 6-HDA treatment noradrenergic control of resistance vessels and cardiac inotropism are reduced significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100777 TI - Extracellular calcium dependence of contraction and endothelium-dependent relaxation varies along the length of the aorta and its branches. AB - Dependence of contraction and endothelium-dependent relaxation of segments of the rabbit aorta and the celiac, superior mesenteric and renal arteries on the presence of calcium in the physiological salt solution in which they were bathed have been studied in vitro. Arteries were tested before and 60 min after removal of Ca++ from the bath solution. Norepinephrine-induced contraction and acetylcholine and A23187-induced relaxation were calcium-dependent in the thoracic and upper abdominal aorta. Contractions were resistant to the effect of calcium removal in segments from the aorta below the origin of the renal artery and from the renal artery itself. The aorta between the superior mesenteric and the renal arteries was intermediate in its dependence. Relaxation of the aorta caudal to the origin of the celiac artery and the renal artery was also resistant. The insertion of an intact everted vessel into an artery whose intima had been inactivated by rubbing restored partially the relaxation to acetylcholine and A23187 in the presence of normal calcium. Vessels that did not relax to acetylcholine after Ca++ exclusion from the bathing solution relaxed when the renal artery was the donor. Donor arteries whose relaxation was sensitive to Ca++ removal did not increase the relaxation response of the renal artery after calcium removal. Diltiazem and D600 reduced the relaxation responses of acetylcholine in the thoracic aorta and enhanced those in the renal artery. It is concluded that there is a transition in the extracellular Ca++ dependence of contraction and endothelium-derived relaxation along the length of the abdominal aorta. Changes in the dependence of contraction occurred more gradually than relaxation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100778 TI - Effects of altered thyroid function on histamine levels and mast cell number in neonatal rat brain. AB - The effects of altered thyroid function on the levels of histamine, histidine decarboxylase activity and the number of mast cells were studied in the brain of 5-day-old rats. At this age both brain histamine levels and mast cells number are at a maximum. In addition the major portion of the amine is stored in mast cells and upon subcellular fractionation it sediments in the crude nuclear fraction (P1). Treatments with thyroid hormones or thyrotropic hormone up to 5 days of age leads to a decrease in the histamine levels and mast cells number in the brain, whereas administration of the antithyroid agent 6-n-propyl-2-thiouracil increases both parameters. All treatments affected only the histamine in the P1 fraction and failed to alter the levels of neuronal histamine which is located in the supernatant of P1 (S1). These facts suggest that in neonatal rat thyroid hormones could be involved in the regulation of the levels of brain histamine by regulating the number of brain mast cells. PMID- 3100779 TI - Functional and physical properties of chick atrial and ventricular GTP-binding proteins: relationship to muscarinic acetylcholine receptor-mediated responses. AB - Activation of muscarinic acetylcholine receptors in chick atria, but not ventricles, causes an increase in K+ permeability. Because of suggestions that this difference in muscarinic receptor-mediated physiological responses may be due to changes in the guanine nucleotide regulatory proteins (termed Go and Gi) associated with the receptor, we compared the functional and biochemical properties of these proteins in atria and ventricles from 8-day chick embryos. The affinity of agonist for the muscarinic receptor in either the absence or presence of guanine nucleotides was the same in membranes from atria and ventricles; similar concentrations of guanyl-5'-yl imidodiphosphate were required to regulate agonist binding in both tissues (EC50 of 2.7 X 10(-8) and 2.0 X 10( 8) M for atria and ventricles, respectively). Forskolin-stimulated adenylate cyclase activity in atria and ventricles was equally sensitive to inhibition by guanyl-5'-yl imidodiphosphate. In addition, the muscarinic agonist carbachol inhibited adenylate cyclase in ventricles with an IC50 similar to that observed in atria, although the magnitude of inhibition was slightly less in ventricles. The physical properties of the alpha subunits of the guanine nucleotide regulatory proteins were examined after covalent modification by islet activating protein. Two [32P]ADP-ribosylated polypeptides were detected by one dimensional gel electrophoresis, with molecular weights equal to those reported for Go and Gi from other tissues. Similar amounts of both proteins were found in atrial and ventricular membranes. Peptide mapping demonstrated that although the 39 and 42 kD proteins had nonidentical peptide maps, atrial and ventricular peptide maps were identical.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100780 TI - Diazepam-sensitive specific binding of phenytoin in rat brain. AB - [3H]Phenytoin binding to rat cortical membrane was significantly enhanced in the presence of diazepam. This binding is saturable, reversible and displacable by unlabelled phenytoin. Analyses of the binding data either by the Scatchard plot or by the displacement curve revealed a high and a low affinity sites with Kd values of 32 +/- 5 nM and 8.5 +/- 1.1 microM, respectively. Similar enhancement of [3H]phenytoin binding was observed when diazepam was replaced by Ro 5-4864 (4' chlorodiazepam) which is selective for the 'peripheral' type benzodiazepine binding sites. In contrast, neither the 'central' type receptor selective agonist clonazepam nor the antagonist Ro 15-1788 enhanced [3H]phenytoin binding. Therefore, it seems that these phenytoin binding sites in rat cerebral cortex are associated with a benzodiazepine site similar to the 'peripheral' type binding site for its selective affinity for Ro 5-4864. However, judging from the micromolar concentrations required for the enhancement of [3H]phenytoin binding, they appear unlikely to be the same 'peripheral' type binding sites as measured by [3H]Ro 5-4864 binding (Kd approx. 1 nM). The micromolar affinity benzodiazepine recognition sites are a possibility, if they indeed exist. PMID- 3100782 TI - Hexoprenaline tocolysis for intrapartum fetal distress and acidosis. AB - Hexoprenaline, a selective beta 2-sympathomimetic drug, was administered to 12 patients with severe distress in labor. The fetal distress was documented by fetal heart rate abnormalities in association with a fetal scalp blood pH of less than 7.20. The mean fetal scalp pH was 7.17 +/- 0.17 before treatment. A 7.5- to 10-micrograms intravenous bolus of hexoprenaline was followed by an intravenous infusion titrated to inhibit uterine contractions. According to protocol, all patients delivered by cesarean section approximately 40 minutes after the bolus injection. The mean cord blood pH was 7.31 +/- 0.06. No infant had a five-minute Apgar score of less than 8, and there were no significant maternal or fetal side effects. PMID- 3100781 TI - Reproductive effects of 6-chloromelatonin implants and/or injections in male and female Syrian hamsters (Mesocricetus auratus). AB - Adult female hamsters were injected each afternoon for 9 weeks with 2.5, 15 or 25 micrograms of melatonin or 6-chloromelatonin (CM). Each drug resulted in a significant dose-related depression in uterine, ovarian and anterior pituitary gland weights. Additionally, plasma and pituitary concentrations of prolactin fell with increasing dose of either indole whereas pituitary levels of LH and FSH were positively correlated with dose. There was no difference in effectiveness between the two drugs. Adult male hamsters treated for 10 weeks with daily afternoon injections of melatonin and a blank beeswax pellet had depressed testicular and accessory organ weights and plasma and pituitary concentrations of prolactin. Implantation of a 1 mg melatonin or CM beeswax pellet in hamsters concurrently receiving daily afternoon injections of melatonin prevented the organ weight and hormonal changes, except for plasma prolactin. Adult male hamsters treated for 10 weeks with daily afternoon injections of CM and a blank beeswax pellet had depressed reproductive organ weights and pituitary and plasma concentrations of prolactin; this depression in hormonal values and organ weights was totally prevented if the CM-injected hamsters were also bearing a beeswax melatonin pellet. In conclusion, 6-chloromelatonin is as effective as melatonin with regards to antigonadotrophic and counter-antigonadotrophic effects in male and female Syrian hamsters. PMID- 3100783 TI - Orthopaedic operations: variation in case-mix over a 10-year period. AB - The variation in case-mix of patients admitted for routine (non-emergency) orthopaedic surgery at a Staffordshire orthopaedic hospital over a 10-year period was studied, with the aid of the BUPA Schedule of Surgical Procedures. Over this period there was a 2% decrease in the total number of operations performed. There was a marked reduction in the number of 'minor' operations performed, and a marked increase in the number of 'major' and more complex operations performed. The overall workload, as judged by estimated surgeons' fees, rose by 43%. This study offers clear support to the claim that the complexity of orthopaedic operations performed has significantly increased over a ten-year period. PMID- 3100784 TI - The opening of R.S.H. (the Royal Society of Health) House on 13th February 1986 by Her Majesty the Queen. PMID- 3100785 TI - Does diet cure cancer? PMID- 3100786 TI - Law enforcement--policing and drug related crime in urban areas. PMID- 3100787 TI - Health education in cross-cultural settings. PMID- 3100788 TI - Profile of local authority pest officers. PMID- 3100789 TI - Health promotion--gimmick or necessity. PMID- 3100790 TI - Candidiasis in Nigerian students. PMID- 3100791 TI - Fluorides in the prevention of dental caries. PMID- 3100792 TI - Menstruation problems in Nigerian students and sex education. PMID- 3100793 TI - Causes of vaginal infections in Nigeria. PMID- 3100794 TI - Potential antiatherosclerotic agents. 5. An acyl-CoA:cholesterol O acyltransferase inhibitor with hypocholesterolemic activity. PMID- 3100795 TI - Synthesis and gastric antisecretory properties of alpha chain diene derivatives of misoprostol. AB - The synthesis and gastric antisecretory activity in dogs of seven alpha chain diene derivatives of misoprostol are described. The key intermediates in the preparation of these compounds were C-9 tert-butyldimethylsilyl enol ethers that were obtained by in situ silylation of cuprate enolates derived from alpha chain unsaturated cyclopentenones. Selenylation chemistry on these intermediates provided the C2-C3 trans dienes that, where possible, were also deconjugated to produce the corresponding C3-C4 dienes. The most interesting structure in this series is the C5-C6 cis, C3-C4 cis/trans (1:1) diene that could not be readily separated chromatographically into its individual geometric isomers. The gastric antisecretory activity of the mixture of isomers was approximately 3 times greater than that of misoprostol by intragastric administration. The separation of undesired diarrheogenic effects from antisecretory activity was significantly improved relative to misoprostol. PMID- 3100796 TI - Conformations of complexes between mitomycin and decanucleotides. 2. Application of the model to mitomycin C derivatives. Extension to covalent binding with adenine. AB - Molecular mechanics simulation of the interactions of important mitomycin C analogues monocovalently bound to DNA models are presented. These analogues included substituents such as p-hydroxyphenyl, 2-mercaptoethyl, and dimethylamidinium on N7 of mitomycin C and the DNA models consisted of d(GCGCGCGCGC)2 and d(GCGCATGCGC)2. The excellent fits and strong binding affinities of these highly potent analogues support the usefulness of the model. The binding of a mitomycin-related N-phenylpyrrole with a carbamoyloxy substituent to 06 of guanine was studied. Finally, a reactive mitomycin intermediate proposed by Moore was shown to interact with DNA in a way consistent with the formation of a covalent adduct. PMID- 3100797 TI - Folate analogues. 25. Synthesis and biological evaluation of N10-propargylfolic acid and its reduced derivatives. AB - N10-Propargylfolic acid (2), which is the closest pteridine analogue of the thymidylate synthase inhibitor N10-propargyl-5,8-dideazafolic acid (PDDF), was synthesized starting from diethyl [p-(N-propargylamino)benzoyl]-L-glutamate (5) and N-(3-bromo-2-oxopropyl)phthalimide (8). The 7,8-dihydro derivative of propargylfolic acid served as a synthetic substrate of Lactobacillus casei dihydrofolate reductase. Propargylfolic acid and its reduced derivatives were weak inhibitors of L. casei thymidylate synthase compared to PDDF. All derivatives of propargylfolate were active against the growth of Streptococcus faecium, but with the exception of 7,8-dihydropropargylfolic acid, all were inactive against L. casei. Although less potent than PDDF, marked inhibition of thymidylate synthase by 2 was observed in permeabilized L1210 cells. PMID- 3100798 TI - Synthesis and gastrointestinal pharmacology of a 3E,5Z diene analogue of misoprostol. AB - A stereospecific synthesis and the gastric antisecretory and diarrheal activity of a 3E,5Z diene analogue of misoprostol are described. The key intermediate in the synthesis was an alpha chain truncated acetylene that was obtained by a cuprate/enolate capture procedure on the corresponding cyclopentenone. Palladium catalyzed coupling of the acetylene with methyl 4-iodo-3(E)-butenoate provided the conjugated enyne. Although selective hydrogenation of the enyne with Lindlar catalyst failed, the desired 3E,5Z diene was obtained with P-2 nickel as catalyst. The diene was about 3 times more potent than misoprostol in inhibiting gastric acid secretion in dogs and also in producing diarrhea in rats. PMID- 3100799 TI - Differential effects of N-terminal modifications on the biological potencies of growth hormone releasing factor analogues with varying chain lengths. AB - The excellent retention of biological potencies observed with human growth hormone releasing factor analogues with chains 29-44 amino acid residues long is suddenly lost when further amino acid residues are removed from the C-terminus. For instance, 1-27 and 1-24 exhibited little biological activity (greater than 1%) in vivo and in vitro in the rat. Studies were made to determine whether this was due to conformational changes rather than simply the loss of amino acids needed for direct receptor interactions. These involved the introduction of mild conformational restraint in the N-terminal region by the introduction of D-amino acid residues previously shown to increase the potency of the 1-29 peptide. D-Ala in position 2, responsible for a 40- to 50-fold increase in activity in the 1-29 species, resulted in little increase in the potency of 1-27 or 1-24 sequences. However, N-terminal acetylation, responsible for a 12-fold increase in 1-29 in vivo potency, caused greater than 50-fold increase in 1-27 potency but had little effect on 1-24 potency. Likewise, D-Asn in position 8 was far more effective in increasing the potency of the 1-27 sequence compared to the 1-29 ([D-Asn8]-GRF(1 29)NH2, 220% vs. [D-Asn8, Leu27]-GRF(1-27)NH2, 53%; in vivo]. This differential effect was even more clear in vitro. The highest in vivo potency in the 1-27 series was achieved with [D-Asp3,D-Asn8,Leu27]-GRF(1-27)NH2 (200%); however, this analogue was still far less potent than its 1-29 counterpart (3800%). None of the D-amino acid substitution strategies were effective in increasing 1-22 peptide potencies to detectable levels. The results indicate that the effect of N terminal substitutions and resulting potencies of the GRFs is very much dependent on chain length, perhaps suggesting that C-terminal amino acids promote conformational effects at the N-terminus and/or vice versa. PMID- 3100800 TI - Polychlorinated biphenyls and related compound interactions with specific binding sites for thyroxine in rat liver nuclear extracts. AB - Thyroid hormone analogues, polychlorinated biphenyls (PCBs), and their derivatives were shown to bind specifically to thyroxine-specific binding sites in rat liver nuclear extracts. The structure-binding relationship for thyroxine binding prealbumin was qualitatively similar to that for the nuclear receptor. In general for both binding proteins, increased binding affinity was seen for the more linear and in some cases rectangular shaped (as opposed to the angular shaped thyroid hormones) chlorinated aromatic hydrocarbons with chlorine concentrated in lateral positions (3,3',5,5'-substitution on biphenyl nucleus). However two groups of compounds showed distinct quantitative differences. The relatively less polar and more lipophilic nonhydroxylated PCBs bound the nuclear receptor with significantly lower affinities while two compounds that are structurally related by the potential for equilibrium interconversion to a rigid planar structure bound with significantly higher affinities. This latter class of compounds represents soluble dioxin (TCDD) approximate isosteres and has an extended (polarizable) pi-system brought about by a planar structure (or conversion to the same) and lateral halogenation. These structure requirements are maximally expressed in 3,3',5,5'-tetrachlorodiphenoquinone (TCDQ), which shows a remarkably high affinity (Ka = 1.84 X 10(11) M-1) for the nuclear receptor. Thus, the nuclear receptor shows the expected structural specificity and sensitivity for possible involvement in the high toxicity of these classes of compounds. The physiological significance of these binding results is supported by the dose-dependent regulation (increase) of the thyroxine nuclear receptor number by dioxin, although the mechanism responsible for this increase is not clear. The nuclear binding component was further analyzed by sucrose density gradient centrifugation and was found to have a sedimentation coefficient of 4.3 S under high salt conditions. A crude estimate of the molecular weight (45,200) was obtained from a linear plot of standard globular protein fraction number (sedimentation coefficient) vs. log molecular weight. Although direct evidence is not provided, the thyroxine nuclear receptor may cooperate with a second receptor in binding the TCDQ type ligand or exists as a multimeric species with binding properties of both prealbumin and the dioxin (or Ah) receptor. PMID- 3100801 TI - Inhibition of aspartic proteinases by peptides containing lysine and ornithine side-chain analogues of statine. AB - The synthesis of two new analogues of statine are reported corresponding to analogues with the lysine side chain and the ornithine side chain. These analogues were designed on the basis of substrate specificity and molecular modeling of three-dimensional structures of the penicillopepsin: Iva-Val-Sta-OEt crystal structure. 4,8-Diamino-3-hydroxyoctanoic acid [LySta] and 4,7-diamino-3 hydroxyheptanoic acid [OrnSta] were synthesized respectively from Boc-Lys(Z)-al and Boc-Orn(Bzl,Z)-al by addition of lithio ethyl acetate to the aldehyde group. The [LySta] derivative was converted to the trichloroethoxycarbonyl derivative and separated into the corresponding 3S,4S and 3R,4R diastereomers. The [OrnSta] derivative was used as a mixture of 3-position diastereomers. These new amino acids were used to prepare the following inhibitors: Iva-Val-Val-[LySta]-OEt and Iva-Val-Val-[OrnSta]-OEt as well as the corresponding synthetic intermediates. Inhibition constants (Ki values) were measured for inhibition of porcine pepsin and penicillopepsin. Both compounds were potent inhibitors of penicillopepsin with Ki values 10-100 times smaller (2.1 and 1.1 nM, respectively) than the Ki of Iva-Val-Val-Sta-OEt (47 nM). In contrast both inhibitors are exceptionally weak inhibitors of porcine pepsin with Ki values greater than 1 microM. These results are correlated with the ability of the basic group in the new inhibitors to bind to aspartic acid-77 in penicillopepsin. PMID- 3100802 TI - 2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 7. Analysis of the effect of 3,5-dialkyl substituent size and shape on binding to four different dihydrofolate reductase enzymes. AB - A group of trimethoprim (TMP) analogues containing 3,5-dialkyl(or halo)-4-alkoxy, -hydroxy, or -amino substitution were analyzed in terms of their inhibitory activities against four dihydrofolate reductase (DHFR) isozymes. Although selectivities were lower than with TMP, the activities against vertebrate DHFR were usually at least 2 orders of magnitude less than against enzymes from microbial sources. However, the profiles of activity were remarkably similar for rat, Neisseria gonorrhoeae, and Plasmodium berghei enzymes in all three series, although somewhat different for Escherichia coli DHFR, leading to the conclusion that the hydrophobic pockets are similar for the first three isozymes. Optimal substitution was reached with 3,5-di-n-propyl or 3-ethyl-5-n-propyl groups. Branching of chains at the alpha-carbon, which resulted in increased substituent thickness, was detrimental to E. coli DHFR inhibition in particular. MR is an inadequate parameter for use in correlating such substituent effects. Conformational changes of the more bulky inhibitors can be invoked to explain some differences in inhibitory pattern. Although log P explains simple substituent effects with the vertebrate DHFRs very well, it is insufficient in the more complex cases described here, where shape is clearly involved as well. Solvent-accessible surface areas were measured for TMP in E. coli and chicken DHFRs, where the coordinates are now known. The environment is more hydrophobic in the latter case; this can also be postulated for rat DHFR, which has a very similar activity profile. As with the mammalian isozymes, N. gonorrhoeae DHFR contains an active site phenylalanine replacing Leu-28 of E. coli DHFR, thus creating a more hydrophobic pocket. A similar replacement may also occur in the P.berghei isozyme. Selectivity for bacterial DHFR is dependent on the nature of the 4-substituent, being low for polar 4-hydroxy compounds but high for polar 4 amino analogues, possibly as a result of solvation differences. With complex substituents, the environment of each atom in the active site must be taken into account to adequately explain structure-activity relationships. PMID- 3100803 TI - Synthetic and enzyme inhibition studies of pepstatin analogues containing hydroxyethylene and ketomethylene dipeptide isosteres. AB - Synthetic details for the preparation of a series of hydroxyethylene and ketomethylene dipeptide isosteres with control of stereochemistry at C(2) are described. Incorporation of the isosteres into peptide sequences derived from pepstatin afforded potent inhibitors of the aspartic protease porcine pepsin. When Leu-OH-Ala or Leu-OH-Phe was substituted for statine [3S,4S)-4-amino-3 hydroxy-6-methylheptanoic acid), inhibitors equipotent to the parent compound were obtained, whereas Leu-OH-Gly was a much less effective replacement for statine. A similar trend was evident in the corresponding ketones. The finding that structural features for good substrates do not closely parallel those for good inhibitors is discussed. PMID- 3100804 TI - Prostaglandin-H synthase inhibition by malonamides. Ring-opened analogues of phenylbutazone. AB - Recent reports of serious concern regarding the safe clinical use of phenylbutazone and its hydroxylated metabolite (oxyphenbutazone) as antiinflammatory agents have prompted the further investigation of ring-opened (malonamide) derivatives as potentially preferable therapeutic derivatives. Earlier reports have claimed reduced toxicity among similar derivatives. These studies reveal the relative degree of prostaglandin-H (PGH) synthase inhibitory activity among a series of malonamide derivatives. Contrary to observations in the pyrazolidinedione series, incorporation of a nonpolar butyl side chain in these malonamides was not beneficial but, rather, detrimental to enzyme inhibitory activity. Although none of the reported nonbutylated malonamides was as potent an inhibitor of this enzyme as phenylbutazone, they all showed some inhibitory activity. PGH synthase inhibitory activity was especially pronounced in the bis(p-hydroxy anilide) derivatives, even extending to succinamide and adipamide derivatives. Of some interest is the observation that all of these p hydroxy anilide derivatives were more potent inhibitors of this enzyme than acetaminophen. PMID- 3100806 TI - Phenotypic expression of natural killer cell associated membrane antigens and cytolytic function of peripheral blood cells from different aged humans. AB - The function and phenotypes of peripheral blood NK cells from different aged adults were examined using a 4 hr 51Cr release NK assay and laser flow cytometry utilizing the Leu-7 and Leu-11 monoclonal antibodies. It was found that there was no difference between aged and young adults in the expression of Leu-7+, Leu-11+, Leu-7-11+ or Leu-7+11+ cells. A significant decrease, however, was seen in both percent representation and absolute number of Leu-7+11- cells in older subjects. When examined by age and gender, women aged 17-59 yr had a significantly lower percent representation and absolute number of Leu-11+, Leu-7-11+ and Leu-7+11+ cells and baseline NK activity than did men of similar age. No differences were seen between men and women aged 60-84 yr. No differences were seen in the degree of augmentation by interleukin-2 of NK function in any group. Our data indicate that NK function is correlated with cells bearing the Leu-11 surface antigen and that the gender of the cell donor is a significant factor in the representation of NK cells and function in persons under 60 yr of age. Studies on age differences in NK number and function must therefore take into account the percent of women in the populations studied. PMID- 3100805 TI - Localisation of the gene for Emery-Dreifuss muscular dystrophy to the distal long arm of the X chromosome. AB - The linkage relationships of the gene for Emery-Dreifuss muscular dystrophy have been analysed in a large American kindred using DNA probes from different regions of the X chromosome. Close linkage was found with the locus for factor VIII, with no recombinants in 12 opportunities (maximum lod score 4.3), and with locus DXS15 (two recombinants in 17 opportunities, maximum lod score 2.9 at 0 = 10 cM). No linkage was found with probes pERT87 and 754, which are closely linked to Duchenne and Becker muscular dystrophies at Xp21. These results confirm a separate localisation on the distal part of the long arm at q27-28 for Emery Dreifuss muscular dystrophy and should provide the basis for prenatal diagnosis and improved carrier detection in this disorder if the linkage is confirmed to be close. PMID- 3100807 TI - Postnatal changes of IgG and IgM levels in squirrel monkeys (Saimiri sciureus). AB - Serum IgG and IgM levels were measured in domestically bred squirrel monkeys (Saimiri sciureus) ranging in age from 0 days to 42 months, as well as in adult squirrel monkeys from the wild estimated to be 60 months or older. The results indicated that the transplacental transfer of IgG occurs in the squirrel monkey but the transferability is lower in the squirrel monkey than in the cynomolgus monkey. Immune response in the squirrel monkey occurs just after birth, as shown by IgM production. PMID- 3100808 TI - Changes in circulating levels of immunoreactive follicle stimulating hormone, luteinizing hormone, and testosterone during sexual development in the rhesus monkey, Macaca mulatta. AB - Basal serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) and the responsiveness of these hormones to a challenge dose of luteinizing hormone releasing hormone (LHRH), were determined in juvenile, pubertal, and adult rhesus monkeys. The monkey gonadotrophins were analyzed using RIA reagents supplied by the World Health Organization (WHO) Special Programme of Human Reproduction. The FSH levels which were near the assay sensitivity in immature monkeys (2.4 +/- 0.8 ng/ml) showed a discernible increase in pubertal animals (6.4 +/- 1.8 ng/ml). Compared to other two age groups, the serum FSH concentration was markedly higher (16.1 +/- 1.8 ng/ml) in adults. Serum LH levels were below the detectable limits of the assay in juvenile monkeys but rose to 16.2 +/- 3.1 ng/ml in pubertal animals. When compared to pubertal animals, a two-fold increase in LH levels paralleled changes in serum LH during the three developmental stages. Response of serum gonadotrophins and T levels to a challenge dose of LHRH (2.5 micrograms; i.v.) was variable in the different age groups. The present data suggest: an asynchronous rise of FSH and LH during the pubertal period and a temporal correlation between the testicular size and FSH concentrations; the challenge dose of LHRH, which induces a significant rise in serum LH and T levels, fails to elicit an FSH response in all the three age groups; and the pubertal as compared to adult monkeys release significantly larger quantities of LH in response to exogenous LHRH. PMID- 3100809 TI - In vivo transcription of bacteriophage phi 29 DNA early and late promoter sequences. AB - The in vivo transcription initiation sites of eight putative phi 29 promoters have been accurately determined: seven of them correspond to early promoters, including the four main ones, and the other corresponds to the only late promoter found in vivo. Comparison of the phi 29 promoter sequences with the consensus sequence for the Bacillus subtilis sigma 43 RNA polymerase suggests that the sigma 43 enzyme is involved in the recognition of the viral early promoters, whereas the late promoter sequences share homology with the consensus sequence only at its -10 region. PMID- 3100810 TI - Regulation of a promoter that is utilized by minor forms of RNA polymerase holoenzyme in Bacillus subtilis. AB - The ctc gene of Bacillus subtilis is transcribed in vitro by the minor RNA polymerase holoenzyme forms, E sigma 37 and E sigma 32. To study the expression and regulation of ctc in vivo, we constructed operon and translational fusions of the ctc promoter region to the lacZ gene of Escherichia coli. Our results indicate that ctc is regulated at the transcriptional level, and that this RNA synthesis is maximally induced at the end of the exponential phase of growth under nutritional conditions which inhibit the activity of the tricarboxylic acid cycle. Analysis of in vitro-constructed deletion mutations extending into the ctc promoter region demonstrated that the region required for this regulation is no greater than 53 base-pairs in length. We also compared the expression of ctc to that of another B. subtilis gene, which is transcribed by E sigma 37 and E sigma 32 in vitro, the sporulation gene spoVG. Although the ctc and spoVG promoter regions are recognized by the same forms of RNA polymerase in vitro, our results show that they differ strikingly in the nutritional and genetic requirements for their expression in vivo. PMID- 3100812 TI - Globin evolution in the genus Xenopus: comparative analysis of cDNAs coding for adult globin polypeptides of Xenopus borealis and Xenopus tropicalis. AB - Globin mRNAs of Xenopus borealis and Xenopus tropicalis have been cloned and sequenced. The nucleotide and derived amino acid sequences were compared with each other and with already available data from Xenopus laevis. This analysis rendered clear evidence that the common ancestor of X. laevis and X. borealis, but not of X. tropicalis, had lost one amino acid of the beta-globins prior to a genome duplication event that preceded the segregation of the former two species. Replacement-site substitutions were used to calculate a rough time scale of genome duplication and species segregation. The results suggest an ancient separation between the X. laevis and the X. tropicalis groups occurring approximately 110-120 million years ago. Analysis of the amino acid chains demonstrated various alterations. However, some functional domains, like heme binding sites and alpha 1 beta 2 contact sites, were subject to a high degree of conservation, indicating the existence of functional constraints on them also in the genus Xenopus. PMID- 3100811 TI - The multiple origins of human Alu sequences. AB - I have analyzed a collection of published human Alu sequences. The compiled sequences show several unexpected features, including a uniform pattern of divergence from their consensus sequence, a mutual divergence that is not correlated with their age, and common features in the genomic DNA flanking the 5' ends of the elements. I suggest that the Alu family of sequences derives from a large pool of precursors and not from a single precursor similar to the family consensus sequence, and that new elements integrate into the genome selectively at oligo-A-rich sites. PMID- 3100813 TI - Codon usage in histone gene families of higher eukaryotes reflects functional rather than phylogenetic relationships. AB - The nucleic acid sequences coding for 23 H3 histone genes from a variety of species have been analyzed using a computer assisted alignment and analysis program. Although these histones are highly conserved within and between highly divergent species, they represent various classes of histones whose patterns of expression are distinctively regulated. Surprisingly, in dendrograms derived from these comparisons, H3 sequences cluster according to their modes of regulation rather than phylogenetically. These clusters are generated from highly distinctive patterns of codon usage within the functional gene classes. We suggest that one factor involved in specifying the differing codon usage patterns between functional classes is a difference in requirements for rapid translation of mRNA. In addition, the data presented here, together with structural and sequence information, suggest a heterodox evolutionary model in which genes related to the intron-bearing, basally expressed H3.3 vertebrate genes are the ancestors of the intronless H3.1 class of genes of higher eukaryotes. The H3.1 class must have arisen, therefore, following duplication of a primitive H3.3 gene, but prior to the plant-animal divergence. Implications of the data presented are discussed with regard to functional and evolutionary relationships. PMID- 3100814 TI - An evolvant of Escherichia coli that employs the L-fucose pathway also for growth on L-galactose and D-arabinose. AB - L-Galactose, D-arabinose, and L-fucose form six-membered rings with identical stereoconfigurations. However, only L-fucose can serve as the sole carbon and energy source of wild-type Escherichia coli K-12. A mutant that can grow on L galactose and D-arabinose was isolated by alternate selection on the two sugars. The L-fucose pathway became inducible by all three sugars. Transduction into the mutant of the wild-type fuc+ region containing both the regulatory and structural genes abolished the novel growth abilities on L-galactose and D-arabinose, whereas transduction into the mutant of a fuc deletion abolished the growth abilities on all three sugars. Introduction of the wild-type fucR+ (which encodes the activator protein for the fuc regulon) on a multicopy plasmid depressed the growth abilities of the mutant on L-galactose and D-arabinose, but not on L fucose. The results suggest that the effector specificity of the activator protein in the mutant was broadened. It is proposed that an adaptive response of an activator-controlled system is more likely than that of a repressor-controlled system to achieve fixation in a population, because the first variant to emerge in response to a novel metabolic demand has a good chance of having an altered specificity of regulation. Such a change entails little or no metabolic liability during the absence of the novel substrate. In contrast, the first variant of a negatively controlled system to emerge has an overwhelming chance of being the result of a random mutation that destroys repressor function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100815 TI - A method for the simultaneous alignment of three or more amino acid sequences. AB - We describe an algorithm for the concurrent comparison of three or more amino acid sequences. The basis of the approach is a progressive evaluation of selected segments from each sequence. Only a small subset of all possible segments from each sequence is compared, and a minimum of information is retained for the trace back of the alignment. As a result, this method has the advantage of being both rapid and minimally consumptive of computer memory when constructing an alignment. This being the case, there are no practical limits on the length of sequences that may be aligned. A computer program for the alignment of three sequences is described, and this method is compared with two three-sequence extensions of the Needleman and Wunsch variety, including a recently published approach. In addition, we have made simultaneous alignments of sets of four and five sequences with this selected-segment method. PMID- 3100817 TI - Influence of lipolysis on the mobilization of 2,4,5,2'4',5'-hexachlorobiphenyl from adipocytes in vitro. AB - Epididymal adipocytes, isolated from rats pretreated with [14C]-2,4,5,2',4',5' hexachlorobiphenyl (6-CB), were utilized to examine the relationship between the mobilization of lipid and 6-CB and to determine whether 6-CB was differentially associated with subcellular organelles over time as has been demonstrated for newly synthesized lipid. Lipolysis, induced by the presence of 8 X 10(-7) M isoproterenol (ISO) for 50 min, depleted approximately 1% of total cellular triacylglycerols (TG) regardless of time from treatment with 6-CB. The percentage of cellular 6-CB released from adipocytes to incubation buffer infranatants was not correlated with the magnitude of lipolysis produced over the 50-min incubation period; nor was the percentage of 6-CB released to the buffers correlated with the length of the incubation period, regardless of the presence of ISO. Although adipocytes responded similarly to lipolytic stimuli independent of time (days) since 6-CB treatment, significant decreases were found in the percentage of 6-CB released from adipocytes over time. The in vitro labeling of this newly synthesized TG in fat cells with [U-14C]glucose or [1-14C]palmitate demonstrated that TG was differentially distributed among adipocyte organelles. Newly synthesized TG was also the first to be mobilized under lipolytic stimulus. 6-CB was not released in a similar fashion, since radioactivity associated with the chemical levels of [14C]-6-CB and glucose-derived 14C in buffers were not correlated over time. 6-CB was found to redistribute to all available lipid pools during the subcellular fractionation procedure and thus did not resemble TG. However, it is possible that 6-CB may exist in equilibrium among organelle fractions and that it becomes sequestered within the nonsoluble lipid compartment with time, thus decreasing its appearance in the soluble buffer infranatants over the experimental time course. PMID- 3100816 TI - Coma and the etiology of violence, Part 1. AB - Coma and the etiology of violence are explored by the author through a review of the literature. Animal studies, post-traumatic psychic disorder studies, post traumatic anger and violence studies, tumor and lesion of the limbic system studies, temporal lobe epilepsy studies, and episodic dysfunction syndrome studies, minimal brain studies are reviewed in Part 1 of this article. Part 2, to be published in a later issue of the journal, will conclude the review with clinical surveys on violent individuals and studies on clinical treatment of violence.These studies reveal the etiologic significance of central nervous system dysfunction in the production of violent behavior. Because central nervous system factors are involved in some instances of violent behavior, physicians clearly have a role in the early identification of potentially violent subjects and in the intervention or treatment of individuals who have been violent toward others. Studies have consistently found that lower socioeconomic groups are more predisposed to brain injury from trauma, and several studies have indicated that this is true for segments of the black community. Therefore, investigations in the relationship between central nervous system injury and violence should be a major goal of the black community. Black physicians should assume a lead role in these inquiries and in the prevention and treatment of violence, specifically black-on-black murder. PMID- 3100818 TI - Freshly prepared rat hepatocytes used in screening the toxicity of blue-green algal blooms. AB - The acute toxicity of extracts of blue-green algae was tested in freshly prepared rat hepatocytes in suspension. The results were compared with the traditional in vivo mouse bioassay. Sixty samples of natural algal blooms from freshwater lakes in Norway, Sweden, and Finland and 14 samples cultured in the laboratory were tested. The mouse bioassay revealed hepatotoxins in a large number of the algae, while neurotoxins were not found. Acute hepatotoxicity in vitro was scored by measurement of leakage of the enzyme lactate dehydrogenase (LDH) from damaged cells and of morphological changes of the cells. The correlation coefficients between mouse toxicity and LDH, mouse toxicity and morphological cell damage, and between LDH and morphological cell damage were 0.812, 0.735, and 0.882, respectively. Consequently, the rat hepatocyte toxicity test seems to be well suited for screening blooms of blue-green algae for the presence of hepatotoxins. PMID- 3100819 TI - Effects of polychlorinated biphenyls on porphyrin synthesis and cytochrome P-450 dependent monooxygenases in small intestine and liver of Japanese quail. AB - The effects of acute exposure to polychlorinated biphenyls (PCBs) on porphyrin synthesis and cytochrome P-450-dependent monooxygenases in the small intestine and liver were studied in male Japanese quail. The birds were dosed orally with the PCB mixture, Aroclor 1242, or the individual PCB isomers, 2,4,2',4' tetrachlorobiphenyl (2-TCB) and 3,4,3',4'-tetrachlorobiphenyl (3-TCB), and were killed 48 h later. All the PCB compounds caused a significant increase in porphyrin content and delta-aminolevulinic acid synthetase (ALA-S) activity in the small intestine and liver. Increases in porphyrins were greater in the small intestine than in liver. However, a smaller increase in ALA-S activity occurred in the small intestine than in liver, suggesting that ALA-S induction is not a major mechanism for the increased porphyrin content of small intestine. All the test compounds significantly increased the cytochrome P-450 content of liver. In the small intestine, cytochrome P-450 content was increased by Aroclor 1242 and 2 TCB but not by 3-TCB. The activity of 7-ethoxyresorufin O-deethylase, however, was increased by all test compounds in both liver and small intestine. In contrast, there was a striking difference between small intestine and liver in the induction of 7-ethoxycoumarin O-deethylase (ECOD) activity by Aroclor 1242. In the liver, ECOD activity was unchanged or decreased, but in the small intestine, ECOD activity increased linearly with dose. No tissue difference in ECOD activity was observed after treatment with 2-TCB or 3-TCB. These findings suggest that acute exposure to a given PCB results in marked differences between small intestine and liver in porphyrin metabolism and in the induction of cytochrome P-450 isozymes and associated monooxygenases. PMID- 3100820 TI - A photographically monitored enhanced luminescence enzyme immunoassay for factor VIII related antigen. PMID- 3100821 TI - The effect of schistosomiasis on 24-hour energy expenditure. AB - Twenty-four hour energy expenditure assessment in relation to Schistosoma mansoni infection was carried out in 217 villagers, cleaners of irrigated canals and service personnel. Maximal aerobic power output and sub-maximal response to exercise in the laboratory were also measured. The servicemen were significantly (P less than 0.05) taller and heavier than villagers and canal cleaners. While servicemen and villagers had similar haemoglobin concentration, canal cleaners had significantly reduced (P less than 0.05) haemoglobin values compared to the other two groups. The 24 h energy expenditure was positively correlated with VO2max (r = +0.15, P less than 0.02, n = 215) and negatively correlated with quantitative egg excretion rate (r = -0.16, P less than 0.01, n = 217). Servicemen had the highest recorded values of the 24 h energy expenditure which differed significantly (P less than 0.05) from those of the heavily infected canal cleaners. No significant difference was recorded in 24 h energy expenditure between the lightly infected and non-infected villagers on one hand and servicemen on the other. The findings of this study clearly demonstrated the adverse effect of a high level of S. mansoni infection on the 24 h energy expenditure. PMID- 3100822 TI - Further observations on the use of gross haematuria as an indirect screening technique for the detection of Schistosoma haematobium infection in school children in Dar es Salaam, Tanzania. AB - The reliability of using visible haematuria as an indirect screening technique to detect Schistosoma haematobium was investigated in 418 school children from Dar es Salaam, Tanzania. The sensitivity of the test varied significantly with the time of urine collection and the portion of the micturition stream examined. Whereas sensitivity was 50% and accuracy 73% in the morning, in the afternoon sensitivity and accuracy had increased to 75% and 97% respectively if terminal urine samples were examined. It is concluded that visible haematuria is a sensitive, highly accurate and reliable indirect screening test for urinary schistosomiasis provided that the method of collection and examination of the urine samples is standardized. PMID- 3100823 TI - DDAVP-induced increases in coagulation factor VIII and von Willebrand factor in the plasma of conscious dogs. AB - Infusion of the vasopressin analogue DDAVP into five normal dogs at doses of 0.1 2.0 micrograms DDAVP per kg body weight induced dose-dependent increases in the plasma content of coagulation factor VIII and von Willebrand factor. Plasma concentrations of von Willebrand factor (determined antigenically as factor VIII related antigen and functionally as coagglutinin cofactor activity) and coagulation factor VIII were measured immediately before and at 10, 30, and 120 min after 10-min intravenous infusions of DDAVP. The greatest increases in coagulation factor VIII were produced with the 2.0 micrograms/kg dose. Ten minutes after infusion the mean increase in coagulation factor VIII was 32 units/dl (concentrations of all indices were reported relative to concentrations in a standard canine plasma pool, arbitrarily assigned a concentration of 100 units/dl) and this increase did not change significantly throughout the duration of the experiment. At 10 min post-infusion, the mean factor VIII-related antigen concentration increased 81 units/dl (dose = 2.0 micrograms/kg) and did not change significantly for the duration of the experiment. The maximum mean increase in coagglutinin cofactor activity, 141 units/dl, occurred 10 min after infusion (dose = 1.0 microgram/kg). Coagglutinin cofactor activity decreased significantly from peak activity by 120 min post-infusion. PMID- 3100824 TI - Cross reactivity of a monoclonal pan T-cell antibody (anti-Leu 4) with prostate epithelium. AB - Cross reactions between monoclonal T-cell antibodies and non-lymphoid tissues have rarely been reported. In this study 28 samples of prostatic tissue obtained at the time of autopsy or surgery, two samples of metastatic prostatic carcinoma and a series of other tumours were snap frozen and sections reacted with a series of monoclonal antibodies directed against the following antigens: Leu 1, Leu 4, T3, T8, T4, T11 and B4. Reactions were detected with an indirect immunofluorescent method. In 10 of 11 normal prostates, 15 of 15 with nodular hyperplasia and 3 of 4 prostatic adenocarcinomas a strong positive reaction occurred with anti-Leu 4. All other antibodies tested were negative. Other tumours tested, including primary carcinomas of lung (2), kidney (3), stomach (1), colon (1), pancreas (1), breast (2), urinary bladder (1), esophagus (1), larynx (1) and malignant melanoma (2), were negative with all antibodies. This is, to our knowledge, the first report of cross reactivity between a monoclonal pan T-cell antibody and epithelium. This cross reaction may be related to a shared antigen between T-cells and prostate epithelial cells or, more likely, it represents reactivity with a shared epitope. Knowledge of this reaction will prevent possible misinterpretations in the evaluation of undifferentiated neoplasms. PMID- 3100825 TI - Pharmacoarteriography in the evaluation of impotence. AB - Progress in diagnosis and therapy of impotence is handicapped by the absence of a validated and objective method for evaluating the vascular system; a gold standard for vasculogenic impotence is needed. Prior experience has indicated that conventional arteriography in unanesthetized patients is unreliable in evaluation of the penile arterial supply. We have improved our arteriographic methods by the routine application of selective pudendal injections, vasodilation pharmacoangiography with nitroglycerin and papaverine, and direct magnification. Experience in 37 impotent patients demonstrates marked improvement in the quality of visualization of distal vessels, and the frequent presence of functional vasoconstriction of medium and small arteries that can be distinguished from organic disease only with vasodilators. We believe these angiographic methods will improve the criteria against which other diagnostic and therapeutic methods can be objectively assessed. PMID- 3100826 TI - Fatal tricuspid valve obstruction due to a large infected thrombus attached to a Hickman catheter. PMID- 3100827 TI - Alanine aminotransferase and posttransfusion hepatitis. PMID- 3100828 TI - Patient compliance and the need to improve it. PMID- 3100829 TI - Evaluation of venom extracts from the cobra snakes (Naja naja) of three different weights and size groups. PMID- 3100830 TI - Diuretic action of garlic extract in anaesthetised normotensive dogs. PMID- 3100831 TI - A study of haemoglobin Barts in cord blood. PMID- 3100832 TI - Human brucellosis in Multan. PMID- 3100833 TI - [The renin-angiotensin, catecholamine system during controlled hypotension with sodium nitroprusside, trinitroglycerine and trimetaphan under balanced anesthesia]. PMID- 3100834 TI - [A comparison of two control methods for managing endtidal CO2 automatically under artificial ventilation]. PMID- 3100835 TI - [Arterial blood gas analysis during bronchography in small infants]. PMID- 3100837 TI - [Bacteriological and clinical study of ciprofloxacin in gonococcal urethritis]. AB - The purpose of this study was to determine the susceptibility of Neisseria gonorrhoeae to ciprofloxacin (CPFX). The MIC's of CPFX against 50 clinical isolates of N. gonorrhoeae was examined and they were between less than or equal to 0.003 microgram/ml and 0.006 microgram/ml including 8 beta-lactamase producing strains. The CPFX was administered orally to 3 groups of 10 cases with gonococcal urethritis, groups being determined by 3 dose levels: a group with 200 mg b.i.d. for 3 days (a total of 1,200 mg), another with 400 mg b.i.d. (a total of 800 mg) and the final group with single administration of 400 mg. The effect of CPFX in the 1,200 mg-administered group was excellent in 3 and good in 7. The effect of the drug in the 800 mg-administered group was excellent in 2 and good in 8. The effect in the 400 mg-administered group was all good. Therefore, the overall cure rate was 100% including 5 patients with beta-lactamase producing gonococcic infection. Side effects were not observed in the 30 cases. PMID- 3100836 TI - [Comparison of in vitro activities of first, second and third generation cephem antibiotics against various pathogens isolated from clinical material in 1985]. AB - In vitro susceptibilities of 2,133 strains of various pathogens isolated from clinical materials in 1985 to various cephem antibiotics were studied using the Showa disk diffusion test. The following antibiotics were evaluated: cephalexin (CEX), cephalothin (CET), cefazolin (CEZ), cefotiam (CTM), cefoxitin (CFX), cefmetazole (CMZ), cefotaxime (CTX), cefoperazone (CPZ), ceftizoxime (CZX), cefmenoxime (CMX), latamoxef (LMOX) and cefsulodin (CFS). S. aureus: Susceptible strains to CET, CEZ, CTM, CFX and CMZ with MICs less than 15 micrograms/ml accounted for 93, 73, 94, 80 and 96% of the strains tested respectively, while those susceptible to CTX, CPZ, CZX, CMX, LMOX and CFS accounted for 91, 65, 53, 96, 65 and 95%, respectively. Susceptible strains to CEX at MICs less than or equal to 20 micrograms/ml were 52%. Prevalence of bacterial resistance to CEX and CEZ, which have been used extensively, was greater than that to CET, CTM or CMZ, showing a bimodal distribution of MICs. The third generation cephems studied, in general, also showed bimodal distributions of MICs. S. epidermidis: Susceptible strains to CET, CEZ, CTM, CMZ, CTX, CPZ and CMX with MICs less than 15 micrograms/ml were more than 82% of the strains tested. S. pyogenes: All strains studied were susceptible to CET, CEZ, CTM, CFX, CMZ, CTX, CPZ, CZX and CMX at MICs less than or equal to 15 micrograms/ml. However, susceptible strains to either LMOX or CFS accounted for 95%, while those to CEX at MICs less than or equal to 20 micrograms/ml accounted for 95%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100838 TI - [A complement-mediated immune lysis test using liposomes for the detection of antibodies to Mycoplasma pneumoniae]. PMID- 3100839 TI - [Combined efficacy of polyamine antimetabolites and cis diamminedichloroplatinum]. AB - The combined antitumor effects of the polyamine antimetabolites, alpha-difluoro methylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), with CDDP were studied using human gastric cancer cells xenotransplanted into nude mice. DFMO (1000 mg/kg in two divided doses) and MGBG (50 mg/kg) were given IP for six consecutive days from the time when the xenotransplanted tumor weighted about 100 mg, and CDDP (3.0 mg/kg) was given IP every other day from the same time. Animals treated with DFMO plus MGBG with or without CDDP as well as with CDDP only displayed suppressed tumor growth, compared to untreated mice. In mice treated with these three drugs, however, tumor growth was rather rapid compared to those treated with CDDP only, although tumoral CDDP levels in animals given DFMO, MGBG and CDDP were higher than those given CDDP only. When DFMO, MGBG and CDDP or DFMO and MGBG were administered, tumoral spermidine and spermine levels decreased markedly. On the other hand, tumor DNA biosynthesis in the CDDP only group dropped markedly 24 hours after the termination of therapy. These results suggest that an alteration in the DNA structure caused by polyamine deficiency may prevent cross-link formation in DNA by CDDP. PMID- 3100840 TI - [Results of radiation therapy with the conformation technic in carcinoma of the uterine cervix]. AB - From 1967 to 1982, 696 previously untreated patients with stage I-III carcinoma of the uterine cervix were treated by radiotherapy alone with the conformation technique. This retrospective analysis was undertaken in an attempt to compare the therapeutic results between external irradiation alone (Group A) and external irradiation combined with intracavitary irradiation (Groups B and C). Local control rates of Groups B and C were 12% higher than that of Group A in stages I II and 25% higher in stage III. Using the two-axial arc technique combined with the conformation technique, the severity and frequency of late rectal and urinary complications were significantly decreased. According to these findings, it was concluded that the conformation technique can be used for whole pelvis irradiation combined with intracavitary irradiation in routine work. PMID- 3100841 TI - [Gastric diverticulum invaded by carcinoma]. AB - Diverticulum of the gastric body is uncommon and the coexistence of this lesion and gastric carcinoma much more. The authors report a case of diverticulum and carcinoma of the gastric body in a 66-year-old woman. The partially resected stomach exhibited a diverticulum, 3 X 3 X 2 cm in size, on the lesser curvature and a carcinoma of the depressed type on the posterior wall. The latter was IIc + III-like advanced carcinoma showing poor differentiation histologically and partly invading the diverticular wall, which had no muscular layer (i.e., pseudo diverticulum). As for pseudodiverticulum, carcinoma cells invading the submucosa will reach the serosa easily. It is important not to overlook carcinomas in or around the diverticulum. PMID- 3100842 TI - [Factor VIII inhibitor postpartum]. PMID- 3100843 TI - [A case of atypical hairy cell leukemia--hairy cells expressed Leu 1 antigen after treatment with TPA]. PMID- 3100845 TI - [Discrimination of false positive ST depression by HR-ST and anaerobic threshold ST relationships during the exercise test]. PMID- 3100844 TI - [Intraperitoneal bleeding due to postpartum factor VIII inhibitor]. PMID- 3100846 TI - [Enzyme-linked immunosorbent assay for the detection of anti-ENA antibodies]. PMID- 3100847 TI - Differences in tumor necrosis factor productive ability among rabbits. PMID- 3100848 TI - [Effect of daily intake of carbohydrate, protein and fat on serum levels of HDL cholesterol and apolipoproteins A-I and A-II]. PMID- 3100849 TI - Effects of a new anti-inflammatory imidazole derivative, fenflumizole, on platelet aggregation in the rabbit. AB - The antiplatelet effect of fenflumizole, compared with aspirin or ticlopidine, was examined in in vitro, ex vivo and in vivo situations of the rabbit. Unlike ticlopidine, fenflumizole and aspirin effectively inhibited in vitro the platelet aggregation elicited by arachidonate and collagen. The activity of fenflumizole was 350 times more potent than that of aspirin. Fenflumizole (0.3-3 mg/kg) given p.o. was 4.2 and 8.1 times more potent than aspirin in inhibiting arachidonate- and collagen-induced platelet aggregations, respectively. Ticlopidine (300 mg/kg, p.o.) resulted in only weak effects on the aggregations. Fenflumizole (3 mg/kg) as well as aspirin (10 mg/kg) given p.o., unlike ticlopidine (300 mg/kg), effectively prevented the arachidonate-induced sudden death. PMID- 3100850 TI - [Prophylactic intravesical instillation therapy with adriamycin (ADM) and mitomycin C (MMC) in patients with superficial bladder cancer]. PMID- 3100852 TI - Relative contribution of dietary protein level and aflatoxin B1 dose in generation of presumptive preneoplastic foci in rat liver. AB - Male weanling F344 rats were orally gavaged with aflatoxin B1 (AFB1) in daily doses of 200, 235, 270, 300, and 350 micrograms/kg/day for a total of 10 doses over a 12-day period, and then 1 week after the last dose they were fed diets of varying protein (casein) content to compare the contribution of AFB1 dose and dietary protein level on the development of presumptive preneoplastic gamma glutamyltransferase-positive (GGT+) foci in rat liver. All animals were fed the same 20% dietary casein level during the dosing period. One week after the end of the dosing period, one-half of the animals in each dose group were then continued on the 20% casein diet for the entire 12-week foci-development period; the remaining half in each dose group were fed lower levels of dietary casein during the foci-development period for the increasing AFB1 dose groups (20, 16, 12, 8, and 4% casein for the 235-, 250-, 270-, 300-, and 350-micrograms/kg/day groups, respectively). The AFB1 dose groups used were determined in a preliminary experiment. In this previous experiment, a clearly discernible threshold dose at about 100-150 micrograms AFB1/kg/day (below which no GGT+ foci were observed) and a steep slope between 150 and 400 micrograms/kg/day were produced. In the second experiment, while the expected positive slope of (AFB1) dose versus (GGT+ foci) response relationship was found for animals fed the 20% casein diet, the dose response for the animals fed the lower levels of casein was eliminated, providing evidence that nutrient intake during the postdosing foci development is more rate limiting toward the development of these preneoplastic lesions than is the carcinogen dose. PMID- 3100851 TI - Unscheduled DNA synthesis related to transformation grade of human urothelial cells. AB - Unscheduled DNA synthesis (UDS) was studied by quantitative autoradiography in human urothelial cells of three transformation grades (TGr I-III). Cells incubated in arginine-free medium supplemented with hydroxyurea showed dose dependent UDS after administration of agents injurious to DNA, while the scheduled synthesis of DNA was nearly totally suppressed. UDS was demonstrated after treatment with the ultimate carcinogen N-methyl-N-nitroso-N'-nitroguanidine (CAS: 70-25-7) or with the procarcinogen 4-nitroquinoline-1-oxide (4-NQO; CAS: 56 57-5). In cultures treated with benzo[a]pyrene (CAS: 50-32-8), which requires a different activation system than that for 4-NQO, UDS was less pronounced. In 9 cell lines the average rates of UDS were inversely related to TGr. Two cell lines showed a different pattern. PMID- 3100853 TI - [Comparison of in vitro antimycobacterial activities of ansamycin and rifampicin]. PMID- 3100854 TI - [Care of the elderly in U.S.A.: day care center. Long term care]. PMID- 3100855 TI - [Heart-lung transplant; coronary arteries spasm]. PMID- 3100856 TI - [Care of the elderly in U.S.A.: new efforts]. PMID- 3100857 TI - [Duration of total parenteral feeding in acute pancreatitis patients]. PMID- 3100858 TI - [Stabilizing surgery in sequelae of injuries of the ankle joint]. PMID- 3100859 TI - [Acyclovir versus trifluorothymidine in the therapy of stromal herpes keratitis]. AB - A randomized prospective double-blind trial with topical acyclovir (ACV) versus trifluorothymidine (TFT) was performed in the treatment of stromal keratitis. Resolution occurred in only one case (ACV). In all other cases the disease progressed, so that antiviral therapy was discontinued. PMID- 3100860 TI - [Aldose reductase inhibitor--a new way for preventing diabetic lens changes?]. AB - Increased blood sugar levels may influence the refractive power of the lens in juvenile diabetics, and can lead to the rare true diabetic cataract ("snow-storm cataract"). Surplus glucose induces accumulation of the sugar alcohol within the cells, thus generating disturbances of the osmotic balance and finally causing cataract. The enzyme aldose reductase catalyzes the formation of sorbitol. Experiments with animals have shown that aldose reductase inhibitors can prevent the formation of such opacities with streptozotocin-induced diabetes in rats. Numerous aldose reductase inhibitors are now known, but we still have insufficient knowledge to determine whether systemic or local administration is preferable. The mechanisms reported here are not relevant with respect to the frequent occurrence of senile cataract in older diabetics, which has often been described. PMID- 3100861 TI - [Cholestasis in total parenteral nutrition--a review]. AB - Intrahepatic cholestasis is a frequent, however unresolved complication of total parenteral nutrition in infancy. A frequency of 10-50% is reported. The concentration of serum bile acids seems to be a sensitive indicator for a beginning cholestasis. As typical histological alterations of the liver are considered: inflammatory portal reaction, fibrosis and proliferation of bile ducts. As important components of the obviously multifactorial etiology are considered: lacking oral alimentation, fetal bile acid synthetic pathways, amino acid toxicity, hypoalbuminemia, sepsis and substrate excess. PMID- 3100862 TI - [Neonatal spasms--a review of symptoms, etiology, therapy and prognosis]. AB - Seizures in the newborn are a distinctive sign of underlying disease. Different convulsive patterns are described. The most common neurologic syndrome consists of subtle seizures. The most important cause is ischemic encephalopathy. Hypocalcemia is the main metabolic disease. Hypoglycemia seems not to be of special relevance for pathogenesis of newborn seizures. Other episodic symptoms of non-epileptic origin should be considered in the differential diagnosis. It is critical to diagnose the cause and to treat it, since the prognosis depends on the underlying disturbance. Phenobarbital is the anticonvulsive drug of first choice. Duration of treatment is determinated of an preexisting brain damage. Newborns with normal neurological evaluation don't need any longer anticonvulsive treatment after cessation of seizures. The EEG is an important prognostic tool. PMID- 3100864 TI - [Retrograde cholecystocholangiopancreatography in emergency surgery of the biliary tract and pancreas]. PMID- 3100865 TI - [Individual characteristics of water-mineral metabolism during 120-day head-down tilt hypokinesia and the effectiveness of prophylactic measures]. AB - Sodium balance and circulating plasma, intracellular, extracellular and interstitial fluid volumes were measured in the test subjects exposed for 120 days to head-down tilt at -5 degrees. The large scatter of the above parameters was associated with individual variations and with the use of different countermeasures against demineralization (exercise and drugs-xydiphone and glucamak). The effect of the countermeasures was different both in qualitative and quantitative terms. It appears that the target of their action was different. The best prophylactic effect was seen when exercise and drugs were used in combination. These findings suggest that individual variations of fluid electrolyte metabolism during prolonged hypokinesia are related to the different capacity of tissues for water and electrolytes. PMID- 3100866 TI - [Reaction of the opioid system of sympathectomized rats to immobilization stress]. PMID- 3100863 TI - Long-term effects of nifedipine on carbohydrate and lipid metabolism in hypertensive hemodialyzed patients. AB - To evaluate long-term effects of nifedipine on carbohydrate and lipid metabolism, 15 hypertensive patients undergoing regular hemodialysis treatment were investigated before nifedipine therapy, after 3 and 9 weeks, and 2 weeks after stopping nifedipine therapy. Three weeks following the administration of nifedipine, both glucose and insulin concentrations decreased significantly from 102.1 +/- 2.6 to 94.9 +/- 2.2 mg/dl and from 19.9 +/- 2.9 to 13.9 +/- 1.7 microU/ml and also remained significantly lower after 9 weeks of nifedipine therapy. This effect was paralleled by a fall of noradrenaline and dopamine. Glucagon levels remained constant. Glucose tolerance tests performed during nifedipine medication and 2 weeks after stopping of nifedipine therapy did not differ significantly. An increase of pyruvate, citric acid cycle intermediates, and ketone bodies--but not of lactate--was registered during nifedipine medication. The observed effects were not completely abolished after the 2-week placebo phase. Our data indicate that nifedipine lowers serum glucose values despite decreased insulin and constant glucagon levels in hypertensive hemodialyzed patients. Considering additionally the behavior of catecholamines and organic acids, the effects could be explained by the improvement of peripheral glucose utilization. PMID- 3100867 TI - Medical practice and the HMO. PMID- 3100868 TI - Hypothermic cardiopulmonary bypass: a comparison between alpha and pH stat regulation in the dog. AB - The accepted normal pH of 7.40 may not be optimal at lower temperatures. This study evaluated the effect of maintaining pH in the accepted normal range at hypothermia (group 1, pH stat) or at normothermia (group 2, alpha stat) on organ blood flow and hemodynamics in dogs. The desired pH was achieved at all temperatures by adjusting pCO2. Hypothermia to 20 degrees C was induced by high flow bypass in both groups followed by 45 min of reduced flow before rewarming. In group 1 (n = 10), pH was 7.45 +/- 0.02 at 20 degrees C and in group 2 (n = 11) it was 7.64 +/- 0.01. A greater base excess developed by the end of the low flow period in pH stat animals (-9.4 +/- 1.1 vs -2.8 +/- 0.8, P less than .001) and resulted in continued acidosis after rewarming in the pH stat group compared to those in the alpha stat group (7.32 +/- 0.03 vs 7.38 +/- 0.01, P less than .02). Expressed as a percentage of baseline, regional blood flows after rewarming for group 1 were: brain 112 +/- 8%, renal cortex 48 +/- 8% (P less than 0.005, rewarm vs baseline), renal medulla 36 +/- 9% (P less than 0.005, rewarm vs baseline), epicardium 198 +/- 40% (P less than 0.05, rewarm vs baseline), endocardium 151 +/ 25%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100869 TI - Peptide-steroid interactions in brain regulation of pulsatile gonadotropin secretion. AB - Reproductive function is regulated by an intricate system of peptide, steroid and amine factors interacting within the brain, pituitary and gonads. At no point is the complexity of the reproductive system better exemplified than in the exquisite interplay of factors required to produce and modulate pulsatile gonadotropin secretion. By extension, analysis of the pulsatile secretory pattern of the gonadotropins, as a means of assessing the contribution of these various factors, can reveal interactions too subtle to be detected by the conventional examination of mean gonadotropin concentration. Analysis of the pulsatile secretory patterns of both LH and FSH reveals striking differences between the two gonadotropins in their response to inhibitory, gonadal peptide and steroid factors, suggesting divergent paths of brain-pituitary regulation. Further studies to clarify this disparity in regulation have demonstrated that neutralization of endogenous LHRH completely abolishes pulsatile LH secretion without affecting pulsatile FSH secretion, suggesting the existence of another, as of yet unknown, brain factor which regulates FSH secretion. The feedback signals provided by gonadal steroids can induce both inhibition and facilitation of LHRH and LH secretion. Neurons of the central opiatergic system exert a tonic inhibitory influence on the catecholaminergic neurons regulating LHRH secretion, and are believed to mediate the inhibitory actions of the gonadal steroids on the LHRH system. Withdrawal of the gonadal steroids has been reported to cause a rapid loss of the tonic inhibitory control of the opiate system on LHRH secretion as revealed by a lack of response to naloxone. Reassessment of this system by analyzing the pulsatile pattern of LH secretion, however, reveals that the loss of naloxone effect after gonadectomy occurs very gradually and that an effect can still be obtained up to 2 weeks after the removal of gonadal steroids. These studies provide excellent examples of the complex interplay observed just between selected factors regulating pulsatile gonadotropin secretion. The use of pulsatile gonadotropin analysis is a powerful model, not only for providing greater clarity of known regulatory interactions, but also for revealing new and more subtle levels of control in the brain-pituitary-axis. PMID- 3100870 TI - Tamoxifen and progesterone effects in target tissues during the perinatal period. AB - The biological effects of tamoxifen (TAM), progesterone (P), or a combination of TAM + P were investigated in the uterus and vagina of newborn guinea pigs after short (2 days) and long (12 days) treatments. In both tissues, tamoxifen provoked a significant trophic effect which is indicated by the increase in weight, protein and DNA content. In the uterus, progesterone also provoked an increase in weight, protein and DNA content, but much less than that provoked by tamoxifen. In contrast, in the vagina progesterone had no effect on the weight, protein and DNA content, but progesterone did not block the agonistic effect provoked by tamoxifen. The situation was different when progesterone receptor was concerned. Tamoxifen in both tissues (particularly in the vagina) stimulated the progesterone receptor very significantly. Progesterone blocked the number of specific binding sites of progesterone and the stimulatory effect provoked by tamoxifen. PMID- 3100871 TI - Advantages of the combination therapy in previously untreated and treated patients with advanced prostate cancer. AB - In order to achieve a more complete blockade of androgens of both testicular and adrenal origin at the start of treatment, we have administered the pure antiandrogen Flutamide in association with orchiectomy (13 patients) or the LHRH agonist [D-Trp6]LHRH ethylamide (118 patients) to previously untreated patients with clinical stage D2 prostate cancer. The mean duration of treatment was 491 days (102-1208 days). The response was assessed according to the criteria of the U.S. National Prostatic Cancer Project. A complete response has been observed in 30 patients (23%) while partial and stable responses have been achieved in 50 (38%0 and 45 (34%) patients, respectively. A positive objective response has thus been observed in 125 of 131 patients (95%). Serum PAP became normal before 6 months in all except 8 (6.1%) of patients. Quite remarkably, 23 of 48 patients treated for 2 years (47.9%) have achieved a complete response. Of the 20 deaths, 12 (9%) were due to prostate cancer, while 8 (6%) resulted from other causes. The probability of continuing a positive response after 2 years of treatment (according to Kaplan and Meier) is 60% while the probability of survival at the same time interval is 89%. This survival should be compared to values of approx 50% achieved with previous treatments limited to inhibition of testicular androgen secretion or action. The present data demonstrate that the combined blockade of androgens achieved with Flutamide and castration provides an objective response in approx 95% of patients, and markedly prolongs the period of remission while the death rate within the first 2 years is lower than that obtained with previous treatments. The important prolongation of survival is achieved with an excellent quality of life. Two-hundred and three patients have clinical stage D2 prostate cancer previously treated by orchiectomy, estrogens or LHRH agonists alone received, at the time of relapse, the same combination therapy. Patients already castrated received only Flutamide while, for those previously treated with DES, the estrogen was replaced by the LHRH agonist [D Trp6]LHRH ethylamide in association with Flutamide. Flutamide was given as additional medication to those already receiving an LHRH agonist alone. Complete, partial and stable objective responses assessed according to the criteria of the U.S. National Prostatic Cancer Project were obtained in 11 (5.4%), 17 (8.4%) and 38 (18.7%) patients, respectively, for a total objective response rate of 32.5%. Progression continued in 137 (67.5%) patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3100872 TI - The relative buffering power of cardioplegic solutions. AB - Those factors that prolong myocardial tolerance to global ischemia constitute an important prerequisite for effective cardioplegia. This study contrasts the relative buffering power of bicarbonate-based and tromethamine-based hyperkalemic crystalloid cardioplegic solution with histidine protein-type buffer (Bretschneider) solution. In addition, the solutions were compared with titration of whole blood and myocardial muscle homogenate. PMID- 3100873 TI - Respiratory failure and mechanical ventilation: pathophysiology and methods of promoting weaning. PMID- 3100874 TI - Variable response to inhaled salbutamol of different lung function parameters in healthy children. PMID- 3100875 TI - Structure and function of phosphatidylglycerol-deficient lung surfactant. PMID- 3100876 TI - Functional characteristics of human alveolar macrophages in lung cancer. PMID- 3100877 TI - Efficacy of beclomethasone nasal solution, flunisolide, and cromolyn in relieving symptoms of ragweed allergy. AB - Although three effective topical treatments for allergic rhinitis are available, little information to assist the clinician in choosing among them has been reported. Therefore, we conducted a randomized clinical trial to compare beclomethasone nasal solution, flunisolide, and cromolyn with placebo in 120 patients with hay fever during the ragweed season of 1984. We found that all three agents were superior to placebo (P less than 0.001) and that the glucocorticoids were more effective than cromolyn (P less than 0.001). Surprisingly, we also found that these intranasal treatments considerably reduced the symptoms of seasonal asthma. Further study of this therapeutic advantage is needed. PMID- 3100878 TI - Cost-effectiveness analysis of end-stage renal disease treatments. AB - The cost-effectiveness of various end-stage renal disease (ESRD) treatments was compared using two different cost measures. The first measure, gross social costs, excluded output gains due to treatment, whereas the second measure, net social costs, included output gains from both market and nonmarket activities. The cost-effectiveness criterion was the cost-per-life year gained or the implicit value of a year of life. The lower the cost-per-life year gained, the more cost-effective the treatment was. Four ERSD treatments were evaluated over 20 years. Home dialysis and transplantation were more cost-effective than in center dialysis, regardless of whether gross or net social costs were used. However, lower values were obtained in the case of net social costs reflecting a provision for output gains due to treatment. The use of net social costs also resulted in greater variations in costs-per-life year gained by age. Changes in survival probabilities affected the results for transplant patients and dialysis patients differently. PMID- 3100879 TI - Case mix of public patients in skilled nursing facilities in Connecticut. AB - The case mix of publicly funded residents in 73 skilled nursing facilities (SNFs) in two Connecticut counties was examined. Data collected in 1980-1981 for utilization review by a professional standards review organization were used for the analysis. The findings indicate that considerable variation exists in case mix across the SNFs. Medicaid per diem rates, which are based on historic costs, have a low and negative correlation with case mix. Case mix indices are significantly higher for rural facilities, with a for-profit type of ownership, and with less than 75% of the bed days devoted to Medicaid residents. PMID- 3100880 TI - Alcoholism treatment and potential health care cost saving. AB - In 1979, MEDICAL CARE published a supplement that summarized and evaluated existing research on changes in health care patterns associated with mental health, alcoholism, and drug abuse treatment. This paper, limited to alcoholism treatment, reviews research that has been completed since the 1979 supplement. Considerations of appropriate research methods are discussed, recent studies that have employed a variety of research approaches are reviewed and evaluated, overall findings are summarized, implications and conclusions that can be drawn about offset are discussed, and recommendations for future research are made. These studies have fewer methodologic limitations and utilize larger study groups and longer follow-up periods than did earlier studies. They confirm earlier findings that general health care utilization and costs drop after initiation of alcoholism treatment. PMID- 3100881 TI - Nursing home case mix. Patient classification by nursing resource use. AB - A model is presented for classifying nursing home patients according to nursing resource use. The model is derived from a study of 558 Medicaid nursing home patients in 12 facilities in Virginia. Data were obtained from self-reports of nursing staff for care delivered over a 52-hour period. The measure of care time was validated through concurrent work sampling. Project staff also assessed the patients' health and functional status using a standardized instrument. Using AID analysis patients were classified into six groups that were homogeneous in their use of nursing resources. Patients were initially categorized by presence or absence of conditions requiring specialized care (e.g., nutritional intake problems, quadriplegia, wounds or lesions, coma, and physical rehabilitation potential). For the specialized care category, two groups were formed by presence or absence of a catheter/ostomy. In the nonspecialized care category, four groups were formed by ADL impairment score and assistance required in eating/feeding. Mean resource use for the highest group was nearly four times that of the lowest group. The model accounted for 53% of the variance in nursing resource use. PMID- 3100882 TI - Antibody activity of monoclonal immunoglobulins in myeloma, macroglobulinemia and benign gammapathy. PMID- 3100883 TI - Interleukin-2 (IL-2) and its receptor. AB - The interleukin-2 (IL-2) receptor system which is responsible for T-cell cycle progression is a unique hormone-receptor system in that both the ligand and the receptor need to be induced. In the present article I will review the biological and molecular characteristics of IL-2 and its receptor, as well as the differential triggering and growth requirements that L3T4+ (T4+) helper and Lyt 2+ (T8+) cytotoxic/suppressor T-cells display to respond. The various mechanisms of regulation operating to restrain clonal IL-2-dependent expansion of normal T lymphocytes will be discussed. PMID- 3100886 TI - [Indications for thymectomy]. AB - An absolute indication for thymectomy exists in all cases with tumors of the thymus gland, however, preoperative differentiation between benign and malignant lesions is not always possible even with modern imaging methods. In extensive tumors of questionable operability preoperative transthoracic needle biopsy (guided by CAT-scan) is recommended. After establishing the histological diagnosis, preoperative radio- and/or chemotherapy can be considered. Certain immunological diseases are a relative indication for thymectomy. Its value is proven in myasthenia gravis, questionable however in ulcerative colitis and erythroblastopenia. Systemic lupus erythematosus is a contraindication. PMID- 3100884 TI - Interleukin-2 versus phorbol-ester-induced cellular events in normal T lymphocytes. AB - Activation of primary T-lymphocytes (T-cells) is dependent on interactions with the T3/T-cell antigen receptor complex which results in expression of cell surface receptors for the lymphocytotrophic growth factor interleukin-2 (IL-2). In the present communication we have compared the cellular responses to phorbol ester with IL-2-induced cellular responses. Thus, the effect of respective ligand on T-cell growth, the level of expression and composition of two distinct affinity classes of IL-2 receptors, and phosphorylation of an 80,000 mol. wt cellular substrate for the Ca2+-dependent, phospholipid-dependent protein kinase C (PK-C) was analysed. The results demonstrate that only the high affinity IL-2 receptor class is induced by phorbol esters and that both IL-2 and cell surface expression of its high affinity receptor is required for induction of low affinity IL-2 receptors. Moreover, IL-2 receptor signalling seems not to involve activation of PK-C and the results suggest that another intracellular pathway, distinct from the PK-C pathway which induces high affinity IL-2 receptors, is employed in the transmission of IL-2 growth promoting signals. PMID- 3100885 TI - Malignant B-cells have receptors for and respond to interleukin-2. AB - Interleukin-2 (IL-2) for a long time has been considered as a T-cell specific growth factor which acts through distinct surface receptors present on activated, but not on resting, T-lymphocytes. Recently it has been shown that activated murine and human B-cells also express IL-2 receptors and respond to IL-2 with an increase of DNA synthesis. Some human B-cell malignancies have been reported to react with anti-IL-2 receptor antibodies, but no response to IL-2 has been documented in these cases. Here, in five of 11 B-cell leukemia/lymphoma cases, we identified cells which not only express the IL-2 receptor, but also respond to IL 2 stimulation, as shown by a marked increase of 3H-thymidine incorporation and by differentiation of lymphoma cells. The IL-2-induced 3H-thymidine uptake was completely blocked by a monoclonal antibody to IL-2 receptor, which indicates that IL-2 acted directly through functional IL-2 receptors. PMID- 3100887 TI - [Pancreatitis: conservative therapy]. AB - The treatment of acute pancreatitis is primary conservative independent of the degree of severeness. The aim of our multimodal concept of therapy (stomach tube, catheterisation of urinary bladder, closed peritoneal dialysis, analgetics- peridural catheter-, substitution of volume-electrolytes, colloides, protein, plasma, blood-, antibiotics, heparin H2-receptor blocker, early artificial respiration, insulin, parenteral nutrition-glucose, amino acids, fat-, hemofiltration/-dialysis, percutaneous drainage of liquid formations) is to postpone or to avoid an operation. Only the erosion bleeding or a locally conditioned sepsis ask for an emergency operation. The lethality of the degrees II (n = 30) and III (n = 39) could be decreased to 20.3% in the last 7 years. The follow-up of 55 patients with severe pancreatitis was free of clinical symptoms in 80% with normal exocrine and endocrine function of pancreas. This confirms that the organ itself is mostly intact even in severe cases of pancreatitis, in hemorrhagic-necrotic pancreatitis. PMID- 3100888 TI - [Oto-acoustic emissions and their significance for inner ear research]. AB - In contrast to the formerly held opinion it is now clear that the spontaneous oto acoustic emissions (OAEs) are pure sinus tones. Frequency shifting (small oscillations and a drifting in one of the two directions) causes broadening of the image in Fourier's transformation, especially when being averaged. These spontaneous OAEs can be observed in ears with minimal disturbance--often not yet detectable by means of pure tone threshold. In such ears the synchronisation of the hair-cells is out of order and this leads to the spontaneous OAEs. With increasing sensitivity of the microphones OAEs can be found in more and more ears. A connection between spontaneous and evoked OAEs can be shown when calculating a FFT from the image of an evoked emission: the spectrum is similar to that of spontaneous OAEs from the same ear. TTS situations in spontaneous OAEs: the reduction of the ability of synchronisation cancels the emission, which will reappear after some time (shifted in frequency). To explain the frequency resolution in the cochlea an active filter has been postulated and the OAEs are claimed to be a reflection of the same; in fact, they are one of the proverbial keyholes through which we might gain a glimpse of what is taking place in the cochlea. PMID- 3100889 TI - Reduction of local tumor recurrence by excision with the CO2 laser. AB - This study was undertaken to determine the effect of CO2 laser surgery on the incidence of local recurrence following tumor resection. Thirty female Fisher 344 rats were implanted with R3230AC mammary carcinoma. All tumors were completely excised 18-21 days post-implantation. In 15 animals, the resection was done with a scalpel. Fifteen animals underwent laser excision with the Sharplan 733 CO2 laser (TEMoo, 125 mm handpiece, 25W continuous wave). Primary tumor size was 17.6 +/- 1.4 mm in the scalpel group and 21.2 +/- 6.3 mm in the laser group. Tumor recurred in 14/15 (93.4%) of the scalpel group and 5/15 (33.3%) of the laser group (p less than 0.001). The site of recurrence was incisional in 13/15 (86.7%) of the scalpel group and 3/15 (20%) of the laser group (p less than 0.001). Axillary metastases occurred in 2/15 (13.3%) in each group. The disease-free interval was 26 days in the laser group and 12 days in the scalpel group. The CO2 laser is an effective surgical adjunct to reduce local tumor seeding and recurrence. PMID- 3100890 TI - Use of the CO2 laser for malignant disease of the oral cavity. AB - The CO2 laser has provided the otolaryngologist/head and neck surgeon with a valuable addition in the diagnosis and treatment of malignant disease of the oral cavity. It is also helpful in the treatment of the premalignant clinical leukoplakias of the oral cavity. Carcinoma in situ has been diagnosed and treated successfully with the CO2 laser. The T1 carcinomas of the tongue, floor of mouth, and tonsil can be successfully managed with the CO2 laser. It also offers the patient a relatively painless method of debulking large obstructing tumors. Other advantages of the CO2 laser include hemostasis, precise visualization, and less edema and pain than the conventional techniques. PMID- 3100891 TI - Bactericidal effects of the neodymium:YAG laser: in vitro study. AB - The effects of laser energy on three bacterial strains, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were studied utilizing the neodymium:YAG laser. Cell suspensions of each strain were divided into four groups. In group I, suspensions from each strain were exposed to laser energy densities of 555-3,333 J/cm2. In groups II and III, two artificial dyes, congo red or methylene blue, were added to the suspensions prior to lasing. In group IVa, no laser energy was used, and group IVb was used to measure the bactericidal thermal effects of the laser. It was concluded that: Low dosages of laser energy exceeding 1,667 J/cm2 resulted in a 2 to 8 log decline in the number of viable bacterial colonies in vitro. Compared to the other two bacterial strains, P aeruginosa was the most sensitive to YAG laser irradiation. Addition of methylene blue, a dark-colored dye, enhanced the bactericidal effects of the YAG laser as indicated by the significantly reduced viability of P aeruginosa after irradiation with 2,222 J/cm2. PMID- 3100893 TI - The use of laser in rectal surgery. AB - Ten patients with rectal tumors were treated by surgical excision of the tumor using a CO2 laser Sharplan 733 CO2 laser, Laser Industries Ltd., Israel. The laser permitted sharp excision, evaporization, or fulguration of tissue. Good hemostasis was achieved. Anesthesia was unnecessary in cooperative, calm patients. There was no mortality or morbidity related to the procedure. In five patients with villous adenoma the tumor was resected with one recurrence as yet (followup 4-16 months). Five patients with inoperable carcinoma were treated for palliation with good results. Our preliminary results indicate that the CO2 laser can be a useful asset in rectal tumor surgery, especially in elderly, moribund patients and in the definite treatment of benign tumors of the rectum. PMID- 3100892 TI - Laser myocardial revascularization. AB - A significant number of patients with ischemic heart disease are not candidates for coronary artery bypass or percutaneous transluminal angioplasty and do not respond to medical management. This group includes those who have diffuse coronary artery disease, those with poor ventricular function, and those who have had poor results from previous surgery. Developing a method to directly revascularize the myocardium by creating channels through the ventricular wall has challenged many investigators. Early methods, including needle acupuncture, were successful in the acute phase, but long-term patency could not be achieved. Closure of the channels was due to fibrosis and scarring. Experiments in our laboratory demonstrated that myocardial channels, made with the CO2 laser, remained patent up to five years. Histopathologic examination of the channels showed minimal damage to the surrounding cells in the acute phase. Studies at intervals of two months to two years showed patent endothelialized channels, with no evidence of fibrosis. Channels created in the myocardium protected the ventricle against an ischemic event when the left anterior descending branch of the coronary artery was ligated. Clinical experience with direct myocardial revascularization by CO2 laser indicates it may be a viable method of treating those patients with ischemic heart disease who are not candidates for other forms of management. The treatment and early postoperative follow-up in one patient are described. PMID- 3100894 TI - CO2 laser in cancer surgery of the breast: a comparative clinical study. AB - Review of the literature reveals little to no data regarding the use of the CO2 laser as a surgical modality in the local treatment of breast cancer. This study was undertaken to determine if the CO2 laser is a surgical improvement over the scalpel, influencing patient care during the surgical and postsurgical period. In the author's series, a total of 209 procedures were performed. Within this group, 105 cases were performed with CO2 laser and 104 cases performed with the scalpel. Biopsies were always performed as a separate procedure prior to definitive surgery. This study was not designed to compare cure rates, the medical follow-up period being 1 year. The results of this study demonstrate a significant improvement in patients' postoperative care, surgical technique, and hospital cost-effectiveness. PMID- 3100895 TI - Milliwatt carbon dioxide laser and hepatic surgery in mice: surgical technique and pathology. AB - The milliwatt carbon dioxide laser was used to induce focal lesions and to perform wedge resections in the livers of 75 strain A mice. The procedures were feasible and well tolerated by the mice, with only one postoperative death in the wedge resection group in an early experiment. The hepatic lesions produced by the laser were characterized histologically by an inner area of vaporization, an intermediate area of coagulation necrosis, and an outer rim of cells with variable damage. The lesions healed by fibroblastic proliferation and scar formation with no hepatocytic contribution. The small vessel and bile ductule sealing effect of CO2 laser, together with the sound healing of laser-induced wounds, highlights the usefulness of this modality in liver surgery in general, and suggests its particular application in the treatment of liver trauma and a variety of hepatic focal lesions, neoplastic or otherwise. PMID- 3100896 TI - Inhibition of monoamine oxidase by 3,4-dihydroxyphenyl L-alanine and its analogues. AB - L-3,4-Dihydroxyphenylalanine (DOPA) was found to inhibit type A monoamine oxidase in human placental mitochondria. The inhibition proved to be noncompetitive with the substrate, kynuramine, and the inhibition was completely reversible. D-DOPA was found to inhibit monoamine oxidase in the same way, and the apparent Ki values of L- and D-DOPA were obtained to be 154 microM and 133 microM, respectively. L-alpha-Methyl-DOPA was found to inhibit the MAO activity competitively with the substrate, but studies with other analogues of DOPA revealed that the inhibition required an amino and a carboxyl group at alpha position. The substitution of a hydroxy group at 3 or 4 position of catechol ring with a methoxy group was found to abolish the inhibition of the MAO activity. In addition to type A MAO in human liver and placental mitochondria, type B MAO in liver mitochondria was inhibited by L-DOPA, but type B MAO was less sensitive to L-DOPA. These results were discussed in terms of its possible regulation of the level of biogenic amines in the brain. PMID- 3100897 TI - Effects of cyclosporine and alpha-difluoromethylornithine on the growth of mouse colon cancer in vitro. AB - The growth and survival of mouse (MC-26) colon carcinoma in vitro and in vivo are significantly reduced by inhibitors of polyamine biosynthesis. alpha Difluoromethylornithine (DFMO), is a specific and irreversible inhibitor of ornithine decarboxylase (ODC); the rate-limiting enzyme in polyamine biosynthesis. DFMO treatment inhibits the growth of MC-26 colon cancer cells and decreases MC-26 cell survival both in vitro and in vivo. In the present study, we examined the effects of cyclosporine (CsA) on growth, survival, and polyamine levels in MC-26 colon cancer in vitro. CsA had inhibitory effects on MC-26 colon cancer growth which were similar to DFMO; these effects were blocked by the addition of the polyamine, putrescine. The combination of CsA (8.3 X 10(-4) mM) and DFMO (0.5 mM or 1.0 mM) inhibited MC-26 cell survival to a greater extent than either agent alone. These results suggest that CsA given in combination with other agents which inhibit polyamine synthesis may be useful for the treatment of colon cancer. PMID- 3100898 TI - Thyrotropin-releasing hormone (TRH) acts centrally to stimulate gastric contractility in rats. AB - Changes in gastric contractility induced by intracisternal (ic) injection of thyrotropin-releasing hormone (TRH) or a stable TRH analog, RX77368 [p-Glu-His (3,3'-dimethyl)-Pro NH2] were investigated in 24 h fasted-conscious rats. Gastric contractility was monitored using chronically implanted extraluminal force transducers sutured to the corpus. Response elicited by a standard meal was used as a physiologic standard. Intracisternal injection of TRH (1 microgram) or RX77368 (100 ng), unlike saline, stimulated high amplitude gastric contractions. The stimulation of gastric contractions induced by ic RX77368 was dose dependent (3-100 ng), rapid in onset, long lasting and not mimicked by the intravenous route of administration. Atropine (0.1 mg/kg) partially antagonized and vagotomy totally blocked the RX77368 (100 ng, ic)-induced stimulation of gastric contractility. These results demonstrated that TRH or RX77368 acts within the brain to elicit potent contractions of the stomach; TRH action appears vagally mediated probably through cholinergic mechanism. PMID- 3100900 TI - The transition unit: the bridge between acute and long-term care. PMID- 3100899 TI - MPTP, MPP+ and mitochondrial function. AB - 1-Methyl-4-phenylpyridinium (MPP+), the putative toxic metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), inhibited NAD(H) linked mitochondrial oxidation at the level of Complex I of the electron transport system. MPTP and MPP+ inhibited aerobic glycolysis in mouse striatal slices, as measured by increased lactate production; MPTP-induced effects were prevented by inhibition of monoamine oxidase B activity. Several neurotoxic analogs of MPTP also form pyridinium metabolites via MAO; these MPP+ analogs were all inhibitors of NAD(H)-linked oxidation by isolated mitochondria. 2'-Methyl MPTP, a more potent neurotoxin in mice than MPTP, was also more potent than MPTP in inducing lactate accumulation in mouse brain striatal slices. Overall, the studies support the hypothesis that compromise of mitochondrial oxidative capacity is an important factor in the mechanisms underlying the toxicity of MPTP and similar compounds. PMID- 3100901 TI - Unusual opportunist mycobacteria. PMID- 3100902 TI - The workup of the asymptomatic patient with a positive fecal occult blood test. AB - Twenty-two protocols for working up an asymptomatic patient who has a positive fecal occult blood test were evaluated using existing information on the prevalences of cancers, adenomas and other conditions in such patients; the natural history of colorectal cancer; the effectiveness of screening tests; risks; and costs. The authors estimate the impacts of the 22 workup strategies on outcomes such as the chance of finding an existing cancer or adenoma, risks (bleeding and perforation), and financial costs of different strategies involving rigid sigmoidoscopy, flexible sigmoidoscopy, barium enema, and colonoscopy. Two protocols were particularly effective. The first involves performing a barium enema study and following it with colonoscopy; if colonoscopy is negative, the barium enema study should be repeated. The second is to perform colonoscopy and if it is negative, follow it with a barium enema study. PMID- 3100903 TI - [Radioimmunological and immunological follow-up of toxic goiter remission following radiotherapy and thyroidectomy]. AB - The paper is concerned with a multimodality approach to the assessment of clinical remission in 42 patients after radical therapy of toxic goiter. T4, T3, sigma TSH, delta TSH were determined in the thyrotropin releasing hormone stimulation test (TRH-test); some immunological indices (RFCc, RFCn, RFC1, a stimulation index [SI] LBTR, a migration index [MI] in the LMIT and serum immunoglobulins) were also investigated. The abnormal TRH-test was revealed in 2/3 of the patients (the hypo-TRH-test in 10 and the hyper-TRH-test in 11). A conclusion was made of the appropriateness of the multimodality approach to the assessment of toxic goiter remission after therapy. PMID- 3100904 TI - [Methodological aspects of bone marrow research using 111In-citrin]. AB - A study of 111In-citrin distribution and kinetics in the body of patients without hemopoietic disorder showed the accumulation (up to 20%) of the injected drug in the bone marrow. Organ fixation, elimination and other pharmacokinetic indices confirming 111In-citrin functional applicability for investigation of the red bone marrow were determined shortly after intravenous injection and in 24 h using a total body meter. These data formed the basis for the calculation of radiation exposures and the solution of methodological problems related to a radionuclide study of the bone marrow in cancer and leukemic patients. 111In concentration in the pelvic bones determined with the help of the total body meter, reflected the total red bone marrow functional activity and was in reverse correlation with a RP elimination value. Total body scintigraphy 24 h after the drug administration made it possible to visualize the bone marrow distribution in the body and to reveal signs of general or local disorders of bone marrow functional activity in leukemias or malignant tumors after combination therapy. PMID- 3100905 TI - [Comparison of immune response in patients with bilharziasis (S. mansoni) from Africa south of the Sahara and Antilles]. AB - Retrospective study has been conducted in the parasitic and tropical diseases department of the hospital Cochin, based on observations made between 1966 and 1985 on antibody rates in sera of 709 bilharziasis patients (S. mansoni). This study shows a great difference of immunologic reaction between the group of patients from French West Indies (458 patients) and the one of the group of patients from Africa South of Sahara (189 patients). Such an observation leads the authors to suppose a difference between strains of schistosomes from Black Africa and French West Indies. PMID- 3100906 TI - [Pulmonary bilharziasis caused by Schistosoma mansoni with impairment of general state]. AB - The authors report on one case of pulmonary bilharziosis at Schistosoma mansoni observed in a West-Indian female showing an impairing of her general condition with fever and dyspnea. Diagnosis was brought out by a pulmonary biopsy, after thoracotomy. Treatment by praziquantel was remarkably efficient. Scarcity of symptomatic cases and paucity of pulmonary radiological pictures are opposite of the frequency of pathological lesions in this parenchyma. The authors discuss the physiopathology of pulmonary bilharziosis in both their invading phase and state phase, as well as their frequency. They come to the conclusion that both parasitological examination of stools and biopsy of mucous membrane of rectum are simple, reliable and harmless implements of diagnosis. PMID- 3100907 TI - [New active drugs against the tuberculosis bacillus and other mycobacteria]. PMID- 3100908 TI - [Circulating antigens of Trypanosoma cruzi in patients with Chagas' disease in an endemic area]. PMID- 3100909 TI - Sex-related naloxone influence on growth hormone-releasing hormone-induced growth hormone secretion in normal subjects. AB - The effect of opiate-receptor antagonist naloxone on growth hormone (GH) release after growth hormone-releasing hormone (GHRH) 1-44 administration was investigated in ten normal men and 18 normal women during different phases of their menstrual cycle. Naloxone was infused at a rate of 1.6 mg/h in women and 1.6- and 3.2 mg/h in men, starting one hour before GHRH administration (50 micrograms iv as a bolus). On different day sessions, naloxone, GHRH, or saline were administered as controls. Naloxone infusion reduced the GHRH-induced GH release in normal women. The mean % inhibition of peak GH response was 83% during follicular phase, 46.5% during periovulatory phase, and 77.6% during luteal phase. On the contrary, in normal men, both doses of naloxone infusion were ineffective in blunting the GH response to GHRH. Our studies indicate that naloxone infusion was capable of inhibiting GH release induced by direct stimulation with GHRH in normal women, suggesting an opiate-antagonist action at the anterior pituitary level. The absence of such an effect in normal men strongly indicates a sex dependence of naloxone effects and suggests a role of the sexual steroid environment in opioid modulation of pituitary hormone secretion. PMID- 3100910 TI - The independent effects of dietary weight loss and aerobic training on high density lipoproteins and apolipoprotein A-I concentrations in obese men. AB - Several studies have demonstrated that high density lipoprotein cholesterol (HDL C) is increased after either dietary weight loss or aerobic exercise training, but it is unclear whether the effects of these two interventions are separate and independent, or just related to the amount of weight or fat lost. The effect of dietary weight loss or aerobic training on apolipoprotein A1 (Apo-A-I) has not been extensively studied. In the present study we evaluated the effects of either dietary weight loss or aerobic exercise training on lipoproteins and Apo A-I, and assessed whether they are related to changes in body composition. Twenty-six obese, otherwise healthy, untrained, nonsmoking, male subjects were weight stabilized for ten days, during which maximal aerobic capacity, body composition, and fat cell size were measured. At the end of this ten-day period lipoproteins and Apo A-I were measured. Subjects were then randomized into either a dietary weight loss (n = 12) or aerobic exercise group (n = 14). At the end of three months the groups were restabilized and restudied. Although both groups lost weight, the weight loss was greater in the diet group (-13.1 v -2.8 kg, P less than 0.001). Important differences in body composition were also detected after the two interventions with 25% of the total weight loss in the diet group coming from fat free mass. Significant decrements in triglyceride (-54 +/- 67 mg/dL, P less than 0.05), total cholesterol (-29 +/- 27 mg/dL, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100911 TI - Homocysteinemia: depressed plasma serine levels. AB - Plasma serine levels were found to be lower than normal (mean +/- SD, 91 +/- 18 mumol/L, n = 16) in homocystinuria patients with a deficiency of cystathionine B synthase on folate therapy, compared with healthy adults (121 +/- 25 mumol/L, n = 25, P less than 0.001). Of 13 other patients with elevated plasma total homocysteine, two patients with homocystinuria due to remethylation defects had normal serine levels, while 11 renal transplant recipients with mild elevations of serum creatinine had lower than normal serine levels (100 +/- 28 mumol/L, P less than .05). Treatment of both the pyridoxine responsive and nonresponsive cystathionine B-synthase-deficient patients with betaine, which lowered plasma homocysteine, also normalized plasma serine levels. In the two patients with remethylating defects however, betaine lowered plasma homocysteine levels without changing plasma serine levels. By contrast, treatment of the renal transplant patients with pyridoxine, folic acid, and vitamin B12 (cofactors required for homocysteine metabolism), caused falls in plasma homocysteine levels, with a concurrent decline in plasma serine levels. These findings may be explained in terms of the requirements for serine in homocysteine metabolism, both as a source of methyl carbon atoms in the methylation of homocysteine by N5 methyltetrahydrofolate and as a substrate in the cystathionine B-synthase reaction. During periods of elevated plasma total homocysteine in man, increased amounts of serine may be diverted to lowering plasma homocysteine. PMID- 3100912 TI - Transcriptional regulation of DNA damage responsive (DDR) genes in different rad mutant strains of Saccharomyces cerevisiae. AB - The roles of the RAD genes of Saccharomyces cerevisiae in the regulation of transcription of two DNA damage responsive (DDR) genes were investigated by examining the levels of the DDRA2 and DDR48 transcripts in different rad mutants after exposure to two different DNA damaging agents. Strains carrying mutations in either the RAD3, RAD6 or RAD52 genes were treated with increasing concentrations of 4-nitroquinoline-1-oxide (NQO) or N-methyl-N'-nitro-N nitrosoguanidine (MNNG) and the DDR transcript levels were determined by Northern hybridization analysis. Our results indicate that the RAD3 gene is required for DDRA2 transcript production following NQO or MNNG treatments. Strains carrying mutations in either the RAD6 or RAD52 genes show an increased level of DDRA2 transcript in undamaged cells. However, the rad6 and rad52 mutants show a normal dose-dependent increase in DDRA2 transcript levels after NQO or MNNG exposure. The DDR48 gene appears to be regulated differently from DDRA2 in that this gene is induced in rad3 cells after damaging treatment but transcript induction is severely reduced in both rad6 and rad52 mutant strains. Although the rad mutations influence the kinetics of transcript accumulation, these effects do not account for the altered dose responses of the DDRA2 and DDR48 genes. Our results also demonstrate that the regulation of DDRA2 and DDR48 transcript levels by heat shock treatment is affected less severely in the different rad strains, a result which suggests that the RAD genes play an indirect role in DDR gene control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100913 TI - Mutations in a new chromosomal gene of Escherichia coli K-12, pcnB, reduce plasmid copy number of pBR322 and its derivatives. AB - We describe mutants of Escherichia coli that decrease the plasmid copy number of pBR322 derivatives. One mutant was partially characterized genetically and its mutation, designated pcnB for plasmid copy number, was mapped to approximately 3 min on the E. coli chromosome. This locus is distinct from other genes whose products are known to affect plasmid replication or stable plasmid maintenance. The pcnB mutant strain should be useful for cloning genes into pBR322 that have aberrant or deleterious effects on the cell when present in high copy number. PMID- 3100914 TI - Appearance of uridine 5'-diphospho-N-acetylglucosamine-4-epimerase during sporulation of Bacillus megaterium. AB - In a biosynthetic study of the spore coat of Bacillus megaterium ATCC 12872 spore with galactosamine phosphate as a major component of the outer coat, high performance liquid chromatography (HPLC) and enzyme immunoassay were applied for the measurement of UDP-N-acetylglucosamine-4-epimerase [EC 5.1.3.7] activity and the enzyme protein concentration, respectively. The new HPLC system using an ion pair (or anion-exchange) column allowed us to determine successfully the enzyme activity and its application, proving that the specific activity of the enzyme in the cells increased at the later stage of sporulation. This increase in activity was parallel to the induction of enzyme protein synthesis, which was detected by sandwich enzyme immunoassay using antiserum to the purified enzyme. These results suggested that the regulation of this enzyme is at the genetic level and it plays an important role in the outer coat synthesis in the later sporulation stage of B. megaterium. PMID- 3100915 TI - Characterization of purified Shiga toxin from Shigella dysenteriae 1. AB - Shiga toxin was purified from the culture supernatant of Shigella dysenteriae 1 by ammonium sulfate fractionation, DEAE-cellulose column chromatography and repeated chromatofocusing column chromatography. About 1.6 mg of purified Shiga toxin was obtained from 15 liters of culture with a yield of about 27%. The molecular weight of purified Shiga toxin was estimated to be 62,000. The toxin consisted of A and B subunits with molecular weights of about 30,000 and 5,000 6,000, respectively. The isoelectric point of purified Shiga toxin was 7.0. Purified Shiga toxin showed the following biological activities: lethal toxicity to mice when injected intraperitoneally with an LD50 of 28 ng per mouse; cytotoxicity to Vero cells, killing about 50% of the cells at 1 pg and all of the cells at 10 pg; and fluid accumulation in rabbit ileal loops at a concentration of more than 1 microgram. PMID- 3100916 TI - A monoclonal antibody with broad reactivity to human interferon-alpha subtypes useful for purification of leukocyte-derived interferon. AB - A monoclonal antibody to human interferon-alpha, termed HT-1 antibody, with a broad reactivity to various subtypes of interferon-alpha was prepared. It bound and neutralized all of the four subtypes of E. coli-derived human recombinant interferon-alpha (alpha 1, alpha 2, alpha 4, and alpha 6) tested; it also neutralized human natural leukocyte interferon but only partially. Human interferon-beta and -gamma were not bound. The antibody conjugated to Sepharose beads retained over 90% of human leukocyte interferon induced by Sendai virus. The bound interferon was recovered by acid elution in good yields and in almost pure form (specific activity was about 2 X 10(8) international units/mg protein). The purified interferon showed, in SDS-polyacrylamide gel electrophoresis, an activity profile with major peaks in a mol. wt. range of 17,000-22,000, which completely agreed with the profile shown by polyclonal antibody-purified interferon. Such purified leukocyte interferon-alpha preparations containing most of the naturally occurring subtypes can be useful for clinical and other purposes. PMID- 3100917 TI - [T-PA and APSAC, new fibrinolytics]. PMID- 3100918 TI - Control of prostaglandin E2 synthesis in cultured rat inner medullary collecting tubule cells: the role of calcium. AB - We investigated the role of calcium in basal, ionophore- and hormone-stimulated prostaglandin E2 (PGE2) production by rat inner medullary collecting tubule cells. Basal PGE2 production is significantly decreased in the absence of calcium (4.49 +/- 0.79 vs. 19.99 +/- 3.47 pg/micrograms protein/h, p less than 0.001). No further increment is seen at 4 mM calcium. The ability of the calcium ionophore A23187 to stimulate PG production is proportional to the amount of calcium present in the extracellular space. Bradykinin is a potent stimulus to PG production even in the virtual absence of calcium while arginine vasopressin has only a modest effect. Neither bradykinin nor arginine vasopressin exhibit any further PG stimulation at 1 mM calcium; both bradykinin and arginine vasopressin increase PGE2 production significantly when calcium is increased to a supraphysiologic level. The data suggests an important role for intracellular rather than extracellular calcium in the control of PG production. Bradykinin but not vasopressin display significant calcium-independent stimulatory effects on PG synthesis. PMID- 3100920 TI - Physicians contemplate artificially administered nutrition and hydration. PMID- 3100919 TI - The corporate transformation of medicine in Minnesota: the rationing of health care--is it inevitable? PMID- 3100921 TI - Think zinc. PMID- 3100922 TI - Chloroquine-resistant Plasmodium falciparum malaria in West Africa. PMID- 3100923 TI - Trichinosis--Hawaii. PMID- 3100924 TI - Update: influenza activity--United States. PMID- 3100925 TI - Occupational asthma from inhaled egg protein--Iowa. PMID- 3100926 TI - Measles transmitted in a medical office building--New Mexico, 1986. PMID- 3100927 TI - Measles--Dade County, Florida. PMID- 3100929 TI - Changes in premature mortality--United States, 1984-1985. PMID- 3100928 TI - Rapidly progressive dementia in a patient who received a cadaveric dura mater graft. PMID- 3100930 TI - Influenza A(H1N1) associated with mild illness in a nursing home--Maine. PMID- 3100931 TI - Postservice mortality among Vietnam veterans. PMID- 3100932 TI - Toxic shock syndrome following influenza--Oregon; update on influenza activity- United States. PMID- 3100933 TI - Sex- and age-specific prevalence of heavier drinking in selected states in 1985- the Behavioral Risk Factor Surveys. PMID- 3100934 TI - Salmonellosis in a school system--Oklahoma. PMID- 3100935 TI - Tuberculosis in minorities--United States. PMID- 3100936 TI - Use of supplements containing high-dose vitamin A--New York State, 1983-1984. PMID- 3100937 TI - Youth suicide--United States, 1970-1980. PMID- 3100938 TI - PCB contamination of ceiling tiles in public buildings--New Jersey. PMID- 3100939 TI - Isolation and purification of two human liver UDP-glucuronosyltransferases. AB - Two UDP-glucuronosyltransferases (EC 2.4.1.17) were purified from human liver microsomes. Human liver microsomes were solubilized with Emulgen 911 and the UDP glucuronosyltransferases were separated and purified by chromatofocusing and UDP hexanolamine Sepharose 4B affinity chromatography. One isoenzyme eluted with an apparent pl of 7.4, displayed a subunit molecular weight of 53,000 after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and catalyzed the glucuronidation of p-nitrophenol, 4-methylumbelliferone, alpha-naphthylamine, and estriol, but not that of 4-aminobiphenyl. A second isoenzyme eluted with an apparent pl of 6.2, displayed a subunit molecular weight of 54,000 after SDS PAGE, and catalyzed the glucuronidation of p-nitrophenol, 4-methylumbelliferone, alpha-naphthylamine, and 4-aminobiphenyl, but not that of estriol. Neither of the purified human liver UDP-glucuronosyltransferases employed estrone, beta estradiol, testosterone, androsterone, or 5 alpha-androstane-3 alpha,17 beta-diol as substrate. These enzymes displayed apparent Km values in the same order of magnitude for a given substrate. In general, high concentrations of phosphatidylcholine were required for reconstitution of maximal glucuronidation activity. This report documents the existence of multiple UDP glucuronosyltransferases in human liver. PMID- 3100940 TI - Differential modification of striatal D1 dopamine receptors and effector moieties by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in vivo and in vitro. AB - Both in vivo and in vitro treatments with the irreversible protein-modifying reagent, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), were used to investigate rat striatal D1 dopamine receptor/effector interactions. Peripherally administered EEDQ markedly reduced D1 dopamine receptor binding and D1 dopamine receptor-stimulated adenylate cyclase in a dose-dependent manner. However, EEDQ administered in vivo did not result in functional modification of either the guanine nucleotide-regulatory protein (Ns) or the catalytic subunit of striatal adenylate cyclase as assessed via guanine nucleotide- or forskolin-stimulated cAMP production. Interestingly, the loss in D1 dopamine receptor binding did not correlate directly with observed reductions in dopamine-stimulated adenylate cyclase activity; 40% of D1 dopamine receptor binding was lost with no significant reduction in the Vmax of dopamine-stimulated adenylate cyclase activity. Conversely, the reduction by EEDQ of the adenylate cyclase activity stimulated by the partial agonist SKF38393 was reduced in parallel with EEDQ induced reductions in the D1 dopamine receptor Bmax. However, when SKF38393 stimulated adenylate cyclase activity was potentiated by forskolin, approximately 30% of receptors could be lost with no significant reduction in cAMP production, resembling the pattern observed utilizing the full agonist dopamine. In vivo pretreatment with the specific D1 antagonist, SCH23390, prevented reductions in dopamine-stimulated adenylate cyclase activity and D1 dopamine receptor binding, suggesting that EEDQ acts at the ligand recognition site of the receptor. Unlike in vivo treatment, in vitro EEDQ treatment resulted in dose-dependent decreases in catalytic subunit activity as assessed by forskolin-stimulated cAMP production, indicating that, in vitro, the adenylate cyclase catalytic subunit is vulnerable to EEDQ-induced modification. These data indicate that EEDQ is an effective tool for elucidating the mechanisms and biochemistry of D1 dopamine receptor/effector coupling. PMID- 3100941 TI - Clotrimazole induction of cytochrome P-450: dose-differentiated isozyme induction. AB - Treatment of male rats for 3 days with the N-substituted imidazole, clotrimazole, produced up to a 4-fold induction of hepatic microsomal cytochrome P-450. The monooxygenase activities induced varied with the dose administered. At low doses (less than 25 mg/kg), p-nitroanisole demethylase and aniline hydroxylase activities were induced. Only at higher doses were other monooxygenase activities (erythromycin and ethylmorphine demethylases and cytochrome P-450 metabolic intermediate complex formation from troleandomycin) induced. Microsomal UDP glucuronosyltransferase activity toward morphine was induced at low doses in a manner similar to that of p-nitroanisole demethylase. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of microsomes indicated that low doses of clotrimazole caused the intensification of a 48,000 molecular weight protein band, whereas at high doses, there was a marked intensification of an additional 50,500 molecular weight protein, the same molecular weight band as was intensified in phenobarbital- and dexamethasone-induced microsomes. The observations suggest a phenomenon of "dose-differentiated" isozyme induction for cytochrome P-450. PMID- 3100942 TI - Synergistic effect of retinoic acid and calcium ionophore A23187 on differentiation, c-myc expression, and membrane tyrosine kinase activity in human promyelocytic leukemia cell line HL-60. AB - The effect of the combination of retinoic acid (RA) and calcium ionophore A23187 on cellular differentiation was assessed in promyelocytic leukemia cell line HL 60. RA (10(-10)-2.5 X 10(-8) M) or A23187 (4 X 10(-7) M) alone produced 15-22% differentiated cells as assessed by nitroblue tetrazolium reduction. Exposure of cells for 48 hr to the combination of 4 X 10(-7) M A23187 and 10(-10)-2.5 X 10( 8) M RA resulted in 20-86% of the cells capable of reducing nitroblue tetrazolium, but with no measurable level of nonspecific esterase activity. The combination of A23187 and either dimethyl sulfoxide, 1,25-dihydroxyvitamin D3, or immune interferon failed to produce a synergistic effect on differentiation. Addition of either the calmodulin antagonists, N-(6-aminohexyl)-5 chloronaphthalenesulfonamide and trifluoperazine, or the protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, during treatment with A23187 and RA did not block differentiation. Membrane tyrosine kinase activity was measured in cells treated with A23187 and RA in a nondenaturing gel system using the exogenous substrate poly(Glu:Tyr). Membrane-bound tyrosine kinase activity was not present in untreated or RA-treated cells but was induced by A23187 treatment alone and was markedly increased in cells 48 hr after treatment with the combination of A23187 and RA. Significantly greater reduction in c-myc mRNA levels was also observed 24 hr after treatment with RA and A23187 in comparison to that observed with either agent alone. These results suggest that a Ca2+-mediated process sensitizes cells to the differentiating effect of RA and that this effect is associated with a significant reduction of c-myc expression and the induction of membrane tyrosine kinase activity in this cell line. PMID- 3100943 TI - Nuclear matrix proteins of Physarum polycephalum. AB - The proteins of nuclear matrix preparations from Physarum polycephalum were compared with analogous mammalian fractions by gel electrophoresis, DNA-binding studies and immunological tests. Polypeptides of 28 and 36 K dalton, which dominate in Physarum preparations, differed from calf thymus matrix proteins in that they were basic and showed low affinity to DNA. These polypeptides were present at about 1.2 mg per mg of nuclear DNA. Polypeptides of higher molecular weight occurred in the preparation at about 0.5 mg per mg of nuclear DNA. At least some of the latter proteins showed high affinity to DNA and cross-reacted with the antiserum against calf thymus matrix proteins. PMID- 3100944 TI - [Analysis of the frequency of allelic exclusion of immunoglobulin light chain genes and molecular characteristics of immunoglobulins secreted by hybridomas with expression of both allelic genes]. AB - The investigation of 750 B-lymphocyte hybridoma clones obtained by fusion of mouse myeloma and newborn heterozygous Igk-la/Igk-1b rat splenocytes has revealed that 9,8% of Ig kappa-chain genes are rearranged productively. Seventeen hybridomas secrete kappa-chains of both allelic variants. The analysis of IgM molecules of nine such clones demonstrated that in six cases only one L-chain allotype is present in IgM. Thus for the first time the high frequency of selective association of H and L chains was shown. Evidently this selectively may function as one of the allelic exclusion mechanisms at the Ig assembly stage. PMID- 3100945 TI - Metabolic activation of emodin in the reconstituted cytochrome P-450 system of the hepatic microsomes of rats. AB - Studies were undertaken to elucidate further the mechanism by which emodin, an anthraquinoid mycotoxin and constituent of rhubarb, was converted into a direct acting mutagen to Salmonella typhimurium TA1537 by the hepatic microsomes and the reconstituted cytochrome P-450 system. Emodin was activated into a mutagenic principle(s) in the reconstituted cytochrome P-450 system, and its mutagenicity was significantly higher with the fraction II (P-448 type) than the fraction I (P 450 type) derived from the hepatic microsomes of PCB-induced rats. Thin-layer chromatographic analysis revealed that the purified cytochrome II-a (maximal CO differential spectrum at 448.0 nm and high-spin form) activity converted emodin into 2-hydroxy-emodin, a direct-acting mutagen. PMID- 3100946 TI - Mutagens formed from butylated hydroxyanisole treated with nitrite under acidic conditions. AB - The reaction products from butylated hydroxyanisole treated with nitrite under acidic conditions were investigated for mutagenic activity in Salmonella typhimurium his reversion assay and for DNA-damaging activity using H17 Rec+ (wild) and M45 Rec- (recombinationless) of Bacillus subtilis. The chloroform extract of the reaction mixture showed 9 spots on thin-layer chromatography (TLC). Compounds from 2 spots on the TLC had high mutagenic activity in TA100 without S9 mix, with DNA-damaging activity. The 2 mutagens were then crystallized from the reaction mixture and identified to be 2-tert.-butyl-p-quinone (t-BQ) and the dimer of t-BQ; 3,3'-di-tert.-butyl-biphenyldiquinone-(2,5,2',5') (BBDQ), from their instrumental analysis. The mutagenic activities of t-BQ and BBDQ were determined by Ames test, and the induced mutation frequencies were about 1.9 X 10(-4) (t-BQ) and 8.3 X 10(-5) (BBDQ). PMID- 3100947 TI - The effect of agent treatment time on the induction of sister-chromatid exchanges in mouse bone marrow cells in vivo. AB - The effect of time of agent administration, via intraperitoneal injection, on the yield of SCEs in bone marrow cells of male B6C3F1 mice was determined for cyclophosphamide (CP), 7,12-dimethylbenz[a]anthracene (DMBA) and mitomycin C (MMC). Animals were treated with several doses of each carcinogen/mutagen at 3 different treatment times: -1, +1 and +8 h in relation to the onset of BrdUrd administration. The results of these studies indicate that the optimal treatment time for inducing a maximal SCE response is agent-specific. For CP, the slope of the SCE response was greatest at the +8 h treatment time while the maximal response for DMBA occurred at the -1 h treatment time. For MMC, the slope of the SCE response was independent of treatment time and of the method of bromodeoxyuridine administration (intravenous infusion vs. tablet implantation) but dependent on the laboratory conducting the study (Brookhaven National Laboratory vs. Oak Ridge Associated Universities). Based on the results of these studies, the +1 h acute treatment time is considered optimal for the in vivo cytogenetic evaluation of suspect chemicals for genotoxic activity when bone marrow is used as the target cell population. PMID- 3100948 TI - Comparison of metabolic activation of carcinogens in human, rat, and hamster hepatocytes. AB - The activities to activate and detoxify procarcinogens were compared in intact hepatocytes from humans, Sprague-Dawley rats and Syrian golden hamsters. Mutagenic metabolites that were released from the isolated hepatocytes were detected by mutation induction in co-cultivated Salmonella typhimurium TA98. Hepatocytes from the 3 animal species all activated aflatoxin B1 (AFB1), acetylaminofluorene (AAF) and aminofluorene (AF) and released active metabolites to induce mutation in the indicator S. typhimurium T98. Hamster hepatocytes were more effective than were human and rat hepatocytes to mediate mutation of Salmonella TA98 by AFB1, AAF and AF. Hepatocytes of human and rat failed to mediate mutation by 1-aminopyrene (1-AP). Indeed, at low concentration of 1-AP and 1-nitropyrene (1-NP), the presence of the hepatocytes decreased the number of TA98 revertants. Only at higher concentrations of 1-aminopyrene and 1-nitropyrene did hamster hepatocytes increase mutation frequencies of indicator cells over the control groups. It seems that hepatocytes, particularly human hepatocytes, are better able to absorb and detoxify 1-AP and 1-NP than to activate them. PMID- 3100949 TI - Possible eggshell protein gene from Schistosoma mansoni. AB - We have identified and sequenced a cDNA clone of a mRNA found only in mature female schistosomes. This mRNA is not detectably synthesized by female worms from single sex infections (unisexual females), by males or by the developing miracidia in the eggs. The clone hybridises to a highly abundant polyadenylated mRNA of approximately 1500 nucleotides. The nucleotide sequence of the clone predicts a polypeptide comprising two repetitive regions. A pentapeptide repeat with the consensus sequence Gly-Tyr-Asp-Lys-Tyr, and a region rich in histidine residues. Hybrid selected mRNA translated in vitro with [3H]tyrosine as labelled amino acid yields a polypeptide of 48 kDa (p48) that corresponds to the major [3H]tyrosine labelled translation product of female worm total mRNA. p48 does not label with [35S]methionine and is absent from the translation products of male and unisexual female mRNAs. The amino acid sequence of p48 has significant homologies to silk moth chorion proteins and we suggest that it is one of the major components of the schistosome eggshell probably accounting for the high level of [3H]tyrosine incorporation into the vitellaria of Schistosoma mansoni. The tyrosine content of the polypeptide suggests that it may play a role in phenol oxidase mediated cross-linking of the schistosome eggshell and in support of this we find that mushroom phenol oxidase will cause the specific cross linking of p48 in in vitro translation products. PMID- 3100950 TI - A Trypanosoma brucei mutant resistant to alpha-difluoromethylornithine. AB - Procyclic Trypanosoma brucei brucei strain 366D is susceptible to DL-alpha difluoromethylornithine (DFMO) with an in vitro ED50 value of 225 microM. A mutant of the procyclic strain resistant to 20 mM of DFMO was isolated by serial in vitro passages of the organisms in increasing concentrations of the drug. Drug resistance remains unchanged after at least ten serial passages in the absence of DFMO. The mutant contains the same level of ornithine decarboxylase activity as the wild-type procyclic, and the mutant enzyme exhibits a similar susceptibility toward DFMO as the wild type. Neither the rate of decarboxylation of ornithine, nor the membrane potential in the mutant cell is changed. The only observed change in the mutant is its significantly decreased uptake of DFMO which reaches a saturating level of 18 microM inside the cells; a concentration seven times below the Ki value of DFMO on T. brucei ornithine decarboxylase (130 microM). Apparently, the failure of DFMO uptake in the mutant strain has provided the basis of drug resistance. The results also raise the question on whether the uptake of DFMO by T. brucei is by passive diffusion or by transporter(s) mediation. DFMO does not compete with the uptake of ornithine, arginine or putrescine, and the reverse holds also true. However, the mutant strain cultivated under DFMO for several generations has a greatly enhanced uptake of ornithine and a moderately heightened uptake of putrescine. Both are reduced to the normal level upon further propagations of the mutant strain in the absence of DFMO. PMID- 3100951 TI - The political contest over health care resumes. PMID- 3100952 TI - Drug therapy: flecainide and tocainide. PMID- 3100953 TI - Therapeutic efficacy of oral charcoal in congenital erythropoietic porphyria. PMID- 3100955 TI - The relation of apolipoproteins A-I and B in children to myocardial infarction in parents. PMID- 3100954 TI - Immunity to malaria and naturally acquired antibodies to the circumsporozoite protein of Plasmodium falciparum. PMID- 3100956 TI - Biotechnology firm turning the corner? PMID- 3100958 TI - Divergent genetic codes. PMID- 3100957 TI - Recombinant interleukin-2 directly augments the cytotoxicity of human monocytes. AB - Interleukin-2 (IL-2), originally described as a growth factor required for sustained proliferation of T cells in vitro is a glycoprotein hormone of known structure which appears to be important for the generation of immune responses in vivo. As well as T lymphocytes, B lymphocytes and large granular lymphocytes with natural killer activity (NK cells) can also respond to IL-2. The action of IL-2 seemed to be limited specifically to lymphocytes, however, and the term 'T lymphocytotrophic hormone' was used. Here we provide evidence that human monocytes display a substantially increased cytotoxic activity as a direct and rapid response to human recombinant IL-2 but not to human recombinant glycosylated interferon-gamma (IFN-gamma) or lipopolysaccharide. Our results reveal a previously unknown function of IL-2 and suggest its possible involvement in monocyte-T cell interactions. PMID- 3100959 TI - Peptides containing the cell-attachment recognition signal Arg-Gly-Asp prevent gastrulation in Drosophila embryos. AB - It has recently been suggested that the Arg-Gly-Asp sequence (RGD) forms part of a widespread cell-extracellular matrix recognition system. Analysis of the cell binding sites of vertebrate fibronectin and other extracellular proteins that interact with cell surfaces implicate the same amino acid triplet. Peptides containing this sequence inhibit certain developmental events such as cell-matrix adhesion or cellular migration in vitro and in vivo. The RGD-sequence is also part of the cellular recognition site of the aggregation protein discoidin I in Dictyostelium suggesting that the RGD-recognition system could be universally used. In Drosophila, despite its advanced genetics, very little is known about the extracellular components that are involved in cell movements and morphogenesis. We report here that peptides containing the RGD-sequence prevent gastrulation of Drosophila embryos. The phenotypic effect is similar to that observed in the dorsal-group mutants: no ventral furrow is formed and the embryos lack dorsal-ventral polarity. The specificity of the inhibiting action suggests that the RGD-sequence may also be used by invertebrates to mediate cell attachment phenomena. PMID- 3100960 TI - Sequence similarity. PMID- 3100962 TI - Association of phosphorylation of the T3 antigen with immune activation of T lymphocytes. AB - In human T lymphocytes the antigen receptor (Ti) is associated non-covalently on the cell surface with the invariant T3 antigen which comprises 3 chains: two glycosylated polypeptides of relative molecular mass 26,000 (Mr 26K) and 21K (gamma and delta) and one non-N-glycosylated polypeptide of Mr 19K (epsilon). The proposed function of T3 is to transduce the activation signals delivered via the antigen receptor. Recently we have shown that phorbol esters, which stimulate protein kinase C, can induce phosphorylation of the gamma subunit of the T3 antigen. But the critical question is whether T3 phosphorylation occurs as a normal consequence of immune activation of T lymphocytes. In this respect, it has been shown that immune stimulation of murine T cells results in phosphorylation of Ti-associated polypeptides that may be the functional analogues of the human T3 antigen. We have therefore monitored T3 phosphorylation after exposure of human T cells to antigen or phytohaemagglutinin (PHA). The data show that both stimuli initiate phosphorylation of the gamma subunit of the T3 antigen which indicates that T3 phosphorylation is a physiological response to immune activation. PMID- 3100961 TI - Receptors for B-cell stimulatory factor-1 expressed on cells of haematopoietic lineage. AB - B-cell stimulatory factor-1 (BSF-1) is a T-cell product of relative molecular mass 20,000 (Mr, 20K) initially described as a cofactor required for DNA synthesis by resting mouse B cells stimulated with low concentrations of anti-IgM antibodies. It acts on resting B cells to enhance the expression of class II major histocompatibility complex (MHC) molecules, to prepare these cells to respond more promptly to subsequent stimuli, such as anti-IgM antibodies, and causes the secretion of IgG1 and IgE by B cells stimulated with lipopolysaccharide (LPS). BSF-1 has been shown to stimulate T cell lines, resting T cells and some mast cell lines. Recently, the designation interleukin-4 (IL-4) has been suggested for BSF-1. We report here the existence of high-affinity cell surface receptors specific for BSF-1 on both B and T lymphocytes, and on cells of several other haematopoietic lineages, including mast cell, macrophage and undifferentiated haematopoietic cell lines. Resting B and T lymphocytes express receptors, which increase in number upon activation of B cells with LPS or anti IgM, and of T cells with concanavalin A. Cross-linking of 125I-labelled-BSF-1 to its receptors creates a complex of Mr approximately 80,000. PMID- 3100963 TI - AIDS virus and scrapie protein genes. PMID- 3100964 TI - Stimulation of specific GTP binding and hydrolysis activities in lymphocyte membrane by interleukin-2. AB - Interleukin-2 (IL-2) is a polypeptide growth factor which stimulates the proliferation and differentiation of T lymphocytes. The receptor for IL-2 is expressed on activated T lymphocytes, cloned IL-2 dependent cells and several other cell types. Analysis of the primary structure and of immune-precipitated receptor suggests that this molecule has no intrinsic signal transduction function, unlike other growth factors. IL-2 interaction with a high affinity receptor has been shown, however, to activate the calcium/phospholipid-dependent protein kinase C (PK-C) presumably via phosphoinositide hydrolysis. Members of a family of closely related guanine nucleotide binding proteins (G proteins) regulate a diverse group of metabolic events. Two of them, Gs and Gi, stimulate and inhibit adenylate cyclase activity respectively, and other G proteins are involved in diverse signal transduction system. Another member, Go, has no known function and activation of phospholipase C has been attributed to the action of an unidentified G protein, Gp. Since it has been observed that IL-2 inhibits the catalytic activity of adenylate cyclase and that agents such as PGE2 which stimulate adenylate cyclase activity inhibit the lymphoproliferative response to IL-2, association of GTP binding proteins with IL-2 signal transduction was investigated. In this report we describe for the first time the participation of a GTP binding protein in the action of a polypeptide growth factor, interleukin 2. PMID- 3100966 TI - Clinical assessment centers: a cost-effective alternative for competency development. PMID- 3100967 TI - [Increasing antibiotic resistance in Neisseria gonorrhoeae]. PMID- 3100968 TI - [An unusual form of a frequently occurring venereal disease]. PMID- 3100965 TI - Dopamine-like activities of an aminopyridazine derivative, CM 30366: a behavioural study. AB - The behavioural effects of CM 30366, an aminopyridazine derivative, on dopamine mediated neurotransmissions, have been studied in mice and rats. CM 30366 induced stereotyped behaviour and antagonized haloperidol-induced catalepsy in rats, after parenteral and oral administration. In 6-hydroxy dopamine (6-OHDA)-lesioned mice, CM 30366 induced contralateral rotations and, when injected before 6-OHDA, protected mice against its neurotoxicity. CM 30366 also provoked contralateral rotations when injected directly into the mouse right striatum. After parenteral injection, CM 30366 slightly increased motility in mice, at least at low doses. The stereotypies and rotations (after intrastriatal injection) induced by CM 30366 were antagonized by haloperidol, alpha-methyl-p-tyrosine and reserpine. The effects of CM 30366 were compared to those of direct and indirect dopamine-like drugs. Bromocriptine induced a behavioural profile, which in most aspects, was qualitatively and quantitatively similar to that of CM 30366. Apomorphine was found slightly more potent than CM 30366, but in contrast to the latter, apomorphine-induced stereotypies were insensitive to alpha-methyl-p-tyrosine or reserpine. (+)-Amphetamine and nomifensine were less potent than CM 30366, and unlike CM 30366, induced ipsilateral rotations in 6-OHDA-lesioned mice. These results indicate that CM 30366 is a potent atypical dopamine-like drug of potential therapeutic usefulness. PMID- 3100969 TI - Haptoglobin type in connection with mean age at first breast cancer signs? AB - In breast cancer patients divided into groups according to haptoglobin (Hp) type (519 patients), blood group (ABO) (433 patients) or Rh factor (358 patients) the mean age at first disease manifestation was calculated. The results indicate that in Hp 1 bearers breast cancer appears at significantly lower age (49 years) as compared to Hp type 2-1 (53.3 years) or Hp 2 (53 years). In blood groups the mean age at first cancer signs raises from 48 years in the AB group to 53.1 years in the A group, only the difference between A and AB being significant. However, these preliminary results require confirmation in larger patient series. PMID- 3100970 TI - [Clinical significance of arachnoid cysts]. PMID- 3100971 TI - [Serum valproic acid concentrations in monotherapy with 1, 2 and multiple administrations per day]. PMID- 3100972 TI - [Sleep EEG without or with sleep deprivation in the provocation of epileptic activity in patients with generalized tonic-clonic seizures]. PMID- 3100973 TI - [Prospective randomized study of the effectiveness of clonazepam and diazepam in petit mal status]. PMID- 3100974 TI - Waldenstrom macroglobulinemia and nephrotic syndrome with minimal change lesion. AB - A case of Waldenstrom macroglobulinemia with nephrotic syndrome is reported. Kidney biopsy, revealing only foot process fusion and response to steroid therapy, fits minimal change disease. PMID- 3100975 TI - Prolactin-releasing action of a low dose of exogenous gonadotropin-releasing hormone throughout the human menstrual cycle. AB - Pharmacological doses of gonadotropin-releasing hormone (GnRH) are known to induce prolactin (PRL) release in different pathological states. The same effect can be observed in postmenopausal women and during the phases of menstrual cycle characterized by high estrogen levels. With the aim to evaluate whether nonpharmacological doses of GnRH are also able to induce PRL release, gonadotropin and PRL response to a low dose of GnRH (10 micrograms, i.v. bolus) was evaluated in 70 normal women during different phases of their menstrual cycle. A significant PRL increase was observed in 33% of subjects during the first days of the cycle (menstrual phase; days 1-3 from the beginning of menstrual bleeding: n = 6), in 24% of subjects during early follicular phase (days -10 to -8 from LH peak: n = 17); in 38% of subjects during midfollicular phase (days -6 to -4 from LH peak: n = 8); in 78% of subjects during preovulatory phase (days -2 to -1 from LH peak; n = 9); in 67% of subjects during postovulatory phase (days +1 to +2 from LH peak; n = 6) and in 42% of subjects during midluteal phase (days +5 to +8 from LH peak; n = 24). In brief, the increase of mean PRL levels after GnRH administration was only significant (p less than 0.05) during pre- and postovulatory phases. The percentage of patients who showed a PRL response during the different phases of menstrual cycle was significantly correlated to the mean maximal net increase of LH (r = 0.927; p less than 0.01) and to the mean maximal net increase of FSH (r = 0.926; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100976 TI - Specific release of a novel pituitary polypeptide, 7B2, from rat anterior pituitary cells in vitro by luteinizing hormone-releasing hormone. AB - We have recently purified a novel pituitary polypeptide, designated 7B2. Subsequently, we developed a sensitive and specific radioimmunoassay (RIA) for this novel polypeptide. Our aim in the present study was to investigate the release of 7B2 from rat pituitary induced by various hypothalamic factors [luteinizing hormone-releasing factor (LH-RH), corticotropin-releasing factor (CRF), and growth hormone-releasing factor (GRF)]. The anterior pituitaries were removed from rats and immediately dispersed enzymatically (a mixture of collagenase/dispase/deoxyribonuclease/chicken serum) and plated on collagen coated multiwell plates in culture medium containing 10% fetal bovine serum. After 2 days of attachment period, the medium was replaced with fresh medium every 24 h. The primary cell culture was incubated with various concentrations of LH-RH, CRF or GRF. Subsequently, the concentrations of IR-7B2, IR-LH, IR-FSH, and IR-ACTH released into the medium were quantified by specific RIA. LH-RH, at a concentration as low as 7.5 ng/ml (6 X 10(9) M: dose range 7.5-60 ng/ml) stimulated the release of IR-7B2, IR-LH, and IR-FSH, by 2- to 3-fold, 17- to 18 fold, and 3-fold, respectively, over basal levels. No significant increase of IR 7B2 was observed when stimulated by CRF or GRF at doses as high as 100 ng/ml. In addition, K+ (50 mM) stimulated the release of all the peptides measured. In conclusion, our studies suggest that the novel peptide 7B2 is under LH-RH control and indirectly confirm the immunohistochemical results of its cellular co localization in FSH and LH cells. PMID- 3100978 TI - Hypertelorism in neurofibromatosis. AB - In eight out of thirty-four patients with neurofibromatosis hypertelorism was seen. This hypertelorism was diagnosed by measuring the intercanthal distance and calculating the interpupillary distance from it. The high incidence of hypertelorism in our group of patients (24%) makes its direct association with neurofibromatosis feasible. Moreover, hypertelorism was found exclusively in neurofibromatosis patients with brain involvement (8 out 11) and therefore seems to herald a severe expression of Morbus Recklinghausen. The bones of the face and the base of the skull are mesenchymal structures of neural crest origin and skull dysplasias - e.g. hypertelorism - fit well into the neurocristopathy concept of neurofibromatosis. Its ease of clinical recognition and its presence at birth makes the hypertelorism an early diagnostic criterium. PMID- 3100977 TI - Short photoperiod depresses castration response in female LSH/SsLaK hamsters. AB - This study was designed to examine the effects of short photoperiod (SP) exposure on gonadotropin and PRL levels in the presence and absence of estrogen treatment in ovariectomized LSH/SsLak hamsters. In experiment I, regularly cycling hamsters maintained in long photoperiod (14L:10D) were ovariectomized and Silastic capsules containing 2.0-mm columns of estradiol benzoate (EB) implanted simultaneously into half of the animals. On the following day, half of the animals in each treatment group were transferred to SP (8L:16D). After 20 days of SP or long photoperiod (LP) exposure, all animals were sacrificed by decapitation and their sera and pituitaries saved for hormonal determinations. The experimental protocol in experiment II was similar, except that two groups in each photoperiod received estrogen treatments; one group received 2.0-mm implants of 17-beta-estradiol (E2), whereas a second group received 10.0-mm E2 implants. SP treatment effected a reduction in serum LH and FSH levels in the absence of steroid replacement treatment. EB treatment depressed serum gonadotropin levels in LP animals, but did not alter levels in SP hamsters. In experiment II, LP- and SP-treated animals showed similar responses to E2 treatment, although different responses were noted in the two dosage groups. Pituitary gonadotropin contents became progressively decreased with increasing steroid levels and in certain groups showed SP-induced reductions. Serum and pituitary PRL levels increased in response to steroid treatment, but were not affected by SP treatment. In summary, 20 days of SP treatment caused gonad-independent reductions in gonadotropin levels and appeared to reduce the steroid feedback sensitivity of the hypothalamo pituitary axis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3100979 TI - Iris hamartomata as diagnostic criterion in neurofibromatosis. AB - We have investigated a personal series of 90 patients with the ("classical") peripheral form of neurofibromatosis (NF) for iris hamartomata (IH). Of subjects aged 6 years or older, 97% had IH. IH were unilateral in 8 patients. IH were not found in 44 unaffected first degree relatives of patients with NF or in normal persons seen during the study period. We consider IH a reliable diagnostic criterion to be added to the list of diagnostic features. In childhood the incidence of IH exceeds that of cutaneous neurofibromas and axillary freckling. PMID- 3100980 TI - Hydrocephalus, lissencephaly, ocular abnormalities and congenital muscular dystrophy. A Warburg syndrome variant? AB - The authors report a family in whom three members suffered from congenital hydrocephalus and ocular abnormalities. One of these patients showed along with these symptoms congenital muscular dystrophy. In this child, autopsy disclosed severe cerebral malformations consisting of lissencephaly, arhinencephaly, stenosis of aqueduct, Dandy-Walker cyst and cerebellar micropolygyria. The mode of transmission, the eyes abnormalities and the neuropathological findings of this family resemble the clinical and pathological aspects of Warburg syndrome. However, the presence of congenital muscle dystrophy in one of these children suggests some links with Fukuyama's congenital muscular dystrophy and/or with so called brain-eye-muscle disease of Santavuori. These three syndromes are shortly discussed. The present case and few others reported in the literature obviously represent a severe and lethal form of a congenital disease involving brain, muscle and eyes. PMID- 3100982 TI - Neurofibromatosis presenting with aqueductal stenosis due to a tumor of the aqueduct: case report. AB - A 17-year-old boy with neurofibromatosis presented with delayed puberty and epileptic seizures of recent onset. A computed tomographic scan revealed aqueductal stenosis due to a tumor of the aqueduct. This tumor was found at autopsy to be a pilocytic astrocytoma. Aqueductal stenosis in neurofibromatosis is uncommon and has been considered to be a result of periaqueductal gliosis. This seems to be the first report of neurofibromatosis associated with a tumor of the aqueduct. PMID- 3100981 TI - Long-term anticonvulsant therapy and vitamin D metabolism in ambulatory pubertal children. AB - Parameters of calcium metabolism were thoroughly examined in 28 adolescents with long-term (over 6 years) anticonvulsant therapy (phenytoin, carbamazepine or combination) and in 10 normal controls in September and in March. The adolescents did not receive any vitamin D supplementation during the study. Serum calcium, inorganic phosphorus, parathyroid hormone and alkaline phosphatase levels in the anticonvulsant group did not differ from those of the control group. Serum 25(OH)D and 24,25(OH)2D levels were in all groups consistently higher in September than in March, but no seasonal variation was found in the 1,25(OH)2D levels in any group. The serum 25(OH)D levels in the phenytoin group in March were the lowest among the three groups treated with anticonvulsants, but the levels in the anticonvulsant groups did not differ significantly from each other or from the control group in the same season. The 24,25(OH)2D and 1,25(OH)2D levels in the anticonvulsant groups did not differ significantly from those of control group in September or in March. There was no correlation between anticonvulsant serum free fraction levels and vitamin D metabolites. The bone mineral content in the distal radius was not significantly decreased in the epileptic patients. In conclusion, the long-term anticonvulsant therapy did not induce the so-called "anticonvulsant rickets" in this ambulatory adolescent material. Our data do not indicate that anticonvulsant drugs alter significantly the vitamin D metabolism. Thus, routine vitamin D supplementation does not appear to be indicated in children on anticonvulsant therapy. PMID- 3100984 TI - AIDS policy development within the Department of Defense. PMID- 3100983 TI - Unilateral neglect: personal and extra-personal. AB - Ninety-seven right brain-damaged patients were given two tasks aimed at assessing unilateral neglect in personal and in extra-personal space. The frequency of the two aspects of neglect, as well as their patterns of association with each other and with more elementary neurological disorders are reported and discussed. The results suggest a non-unitary frame of spatial reference for unilateral neglect, which may tentatively be interpreted in terms of a personal vs extra-personal dichotomy. PMID- 3100986 TI - A prospective cost comparison between renal transplantation and chronic hemodialysis at Wilford Hall USAF Medical Center. PMID- 3100985 TI - Airsickness in B-52 crewmembers. PMID- 3100987 TI - The U.S. Army arthroscopic surgery experience. PMID- 3100988 TI - Tuberculin skin tests: atypical mycobacterial PPD-Battey skin test conversion following airborne training. PMID- 3100989 TI - A system for computer-assisted dental emergency diagnosis. PMID- 3100990 TI - Visual hallucinations in children with psychomotor seizures. PMID- 3100991 TI - The preliminary pollutant limit value concept. PMID- 3100992 TI - Exacerbations of Post-traumatic Stress Disorder symptomatology in Vietnam veterans. PMID- 3100993 TI - Collateralization to an occluded cervical internal carotid artery via branches from the ascending pharyngeal artery. PMID- 3100994 TI - Breast cyst aspiration cytology. PMID- 3100995 TI - Etiological and clinical characteristics of diarrhea in young adults, with special reference to shigella gastroenteritis. PMID- 3100996 TI - The use of desmopressin in adult enuresis. PMID- 3100998 TI - Case of diagnosis. Multiple atypical fibroxanthoma. PMID- 3100997 TI - Osteonecrosis of the distal pole of the carpal navicular following fracture. PMID- 3100999 TI - Post-traumatic epilepsy. PMID- 3101000 TI - Medicolegal ramifications of surgical practice. PMID- 3101001 TI - [Electrophysiologic and clinical study of tocainide, a new class IB drug]. PMID- 3101002 TI - [Evaluation of the parameters used in monitoring hypothyroid patients treated with L-thyroxine]. AB - Hormonal and clinical data on 38 tests performed in 7 hypothyroid patients given substitutive treatment with L-thyroxin were analysed. The aim of the survey was to assess the dependability of the various parameters used to estimate dose adequacy in substitutive treatment. Examination of individual cases revealed that overdoses of thyroxin increased T4 to above normal limits without increases in T3, FT3, FT4 or hypophyseal suppression. Chronological discrepancies between clinical data and normal parameters were also noted. However on the data as a whole significant correlations were noted between T4 and TSH (p less than 0.001), between T4 and delta-TSH (p less than 0.001), between T3 and TSH p less than 0.01), between FT3 and delta-TSH (p less than 0.01), between FT4 and delta-TSH (p less than 0.01). FT4 and delta-TSH were also significantly correlated (p less than 0.02) with the Billewicz clinical index of hypothyroidism. It is concluded that the clinical and hormonal data in treated hypothyroid cases have the same significance as in normal or untreated hypothyroid cases. However, it must be borne in mind that unusual relations between the various thyroid hormone fractions including TSH and the standardised clinical examination may arise while doses are being established. In this case the data cannot be automatically interpreted but merely carefully assessed in the light of experience. PMID- 3101003 TI - [Preliminary results of a study of the lymphocyte subpopulations in hemodialysis patients with non-A, non-B hepatitis]. PMID- 3101004 TI - The comparative in vitro activity of spiramycin and erythromycin against Norwegian bacterial isolates. AB - The in vitro activity of spiramycin and erythromycin has been determined by an agar diffusion method against relevant clinical isolates. Generally, erythromycin was more active than spiramycin on a weight-for-weight basis. Spiramycin showed only moderate activity against Haemophilus influenzae and Streptococcus pyogenes. Gonococci were sensitive in vitro to both agents. Many erythromycin-resistant staphylococci were sensitive to spiramycin. PMID- 3101005 TI - Detection of tracking errors by visual climbing fiber inputs to monkey cerebellar flocculus during pursuit eye movements. AB - The activity of cerebellar Purkinje cells was monitored in alert monkeys during visually guided smooth pursuit eye movements. The climbing fiber input evokes 'complex-spikes' which show increased firing during the contralateral phase of sinusoidal pursuit. 'Complex-spike triggered averaging' revealed that the increased firing is a visual response to the retina slip which results from inaccurate tracking. The complex-spikes in turn cause a transient reduction in the simple-spike pursuit command signal that emanates from the flocculus and this may contribute to the corrective eye movement. We postulate that the detection (and possibly the correction) of small errors in motor performance may be a general function of climbing fiber inputs to the cerebellum. PMID- 3101006 TI - Prospective payment and long-term care: linking payments to resource use. PMID- 3101007 TI - Forces guiding the future of nursing research. PMID- 3101008 TI - Rheumatology training enhances students' long-term care skills. PMID- 3101010 TI - Structure and function in circadian timing systems: evidence for multiple coupled circadian oscillators. AB - Considerable progress has been made in elucidating the mechanisms underlying the generation of circadian rhythmicity. This review describes several distinct lines of evidence which converge on the general hypothesis that circadian timing systems consist of multiple circadian oscillators, coordinated by both hierarchical and non-hierarchical coupling relationships. Such a view is supported by the complex phenomenology of circadian systems, as well as by physiological considerations. We have attempted wherever possible to integrate these two sources of evidence, in order to define the current "state of the art" in bridging the gap between structure and function in the analysis of circadian timing systems. While we concentrate mainly on the mammalian, and particularly the rodent, circadian system, we also incorporate comparative evidence obtained from a variety of vertebrate and invertebrate species. PMID- 3101009 TI - The effects of A23187 and phorbol ester on the phosphorylation of proteins in rat anterior pituitary cells. AB - The effects of A23187 and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the phosphorylation of proteins in normal rat anterior pituitary cells were compared. A23187 rapidly activated the phosphorylation of at least 5 proteins (45, 47, 53, 54 and 58 kDa), which reached the maximal level in 2-10 min, and decreased gradually thereafter. In contrast, TPA activated the phosphorylation of at least 6 proteins (45, 62, 64, 72, 76 and 82 kDa), which were mostly distinguished from those activated by A23187. TPA-induced response was elicited more slowly, reached a plateau after about 10 min, and was sustained thereafter. These results suggest that the protein phosphorylation stimulated by A23187 and TPA is conducted by different mechanisms. PMID- 3101011 TI - Utilisation of private hospital beds in Auckland for long term geriatric care. AB - A cross-sectional survey at 25 February 1985 was conducted to determine the utilisation of beds in Auckland's private hospitals. Fifty-three licensed private hospitals accepted patients under the geriatric hospital special assistance scheme (GHSAS). Eighty point eight percent of all patients were receiving public subsidies additional to the universal Department of Health benefit. Ninety-five percent of patients were aged 65 years or more and receiving long term care; of these nearly all had been assessed by a geriatrician and 81.5% were subsidised by the GHSAS. The actual proportion of elderly receiving long term hospital care in Auckland, at 23.3/1000 aged 65 years and over, corresponded closely to newly proposed national guidelines; a previously unrecognised use of private beds for psychogeriatric patients was demonstrated. PMID- 3101012 TI - Antibacterial activity of mupirocin (Bactroban) PMID- 3101013 TI - Cell labelling with indium-111: ten years on. PMID- 3101014 TI - Relationship of fetal hemoglobin and oxygen content to lactate concentration in Rh isoimmunized pregnancies. AB - Fetal blood samples were obtained fetoscopically from 32 Rh isoimmunized pregnancies at 18-32 weeks' gestation, and the hemoglobin concentration, plasma lactate concentration, and oxygen content were measured. When the hemoglobin concentration was more than 8 g/dL, the umbilical arterial and venous lactate concentrations were equal. Abnormal elevations of lactate were found in the umbilical artery at hemoglobin concentrations below 8 g/dL (oxygen content 2 mmol/L) and in the umbilical vein at hemoglobin concentrations below 4 g/dL (oxygen content 2 mmol/L); the arterial lactate values were higher than the venous. These results show that lactate is produced by the human fetus stressed by anemic hypoxia and suggest that compensatory cardiovascular mechanisms are unable to maintain adequate oxygenation to all tissues when the umbilical venous oxygen content falls below 2 mmol/L. PMID- 3101015 TI - A new postpartum syndrome associated with antiphospholipid antibodies. AB - Three women with antiphospholipid antibodies and a postpartum syndrome of pleuropulmonary disease, fever, and cardiac manifestations are presented. Each patient had either lupus anticoagulant or anticardiolipin antibodies or both, but did not have antinuclear antibodies or fulfill the criteria for the diagnosis of systemic lupus erythematosus. No infection or embolus was detected that could explain the pulmonary findings. All three patients had electrocardiographic abnormalities, and one patient developed a cardiomyopathy with extensive immunoglobulin G (IgG), IgM, IgA, and C3 deposition in the myocardium. In addition to the reported association between antiphospholipid antibodies and fetal loss, fetal growth retardation, and preeclampsia, we suggest that patients with antiphospholipid antibodies are at risk for a previously unreported and serious autoimmune postpartum syndrome. PMID- 3101017 TI - [Metastasizing primary duodenal cancer. Extended remission in a patient following chemotherapy]. AB - Extended, especially metastatic primary duodenal cancer is thought to be of extraordinary bad prognosis, and is hardly to be influenced by chemotherapy. In the meantime we were able to achieve a 20-month lasting remission in a patient with metastatic duodenal cancer treated with the FAM-regime. PMID- 3101016 TI - [Metergoline in hyperprolactinemic breast cancer: a phase II study]. AB - The prolactin release inhibiting action of the dopamine receptor agonist metergoline was investigated in 16 patients with metastatic breast cancer associated with hyperprolactinemia. At a daily dose of 12 mg p.o. for 30 days, the drug was highly effective in lowering prolactin levels (day 0: 1076 +/- 171, day 29: 249 +/- 46 mU/l) in these patients. Starting treatment with 4 mg/day, the side effects of the treatment were mild, including dizziness and nausea. PMID- 3101018 TI - [Effect of 2-cyanoethylurea, thymus extract and lithium carbonate on the leukocyte count in peripheral blood following whole body irradiation]. AB - In our investigations the qualification of the substances 2-cyanoethyl urea, thymus extract and lithium carbonate was tested for a potential reducing or shortening of the leukocyte-depression in rats after whole-body irradiation. Intravenous applications of 2-cyanoethyl urea and intramuscular injections of thymus extract showed no effect in Wistar rats not only in increase of leukocyte number of peripheral blood, but also in variation of leukocyte portion in differential blood-count. Leukocytes depression appearing in consequence of whole body irradiation was independent of cyanoethyl urea applications and of thymus extract, too. Lithium carbonate shows a significant increase of leukocytes in peripheral blood in dependence of dosage and frequency of applications. After whole-body irradiation with 7 Gy under lithium therapy, it was shown that on day 6 after irradiation leukocyte number was significantly higher than in controls. Radiogenic leukopenia phase was reduced significantly by lithium. PMID- 3101019 TI - Electron microscopy of impression-acquired conjunctival epithelial cells. AB - The authors describe a technique with which one can perform electron microscopy on conjunctival epithelial cells acquired by impression cytology. With adjacent excisional and impression biopsies of conjunctival epithelium in patients having mucopolysaccharidoses (MPS), typical fibrillo-granular inclusions are shown. This noninvasive procedure has potential for the study of subcellular, cellular, and intercellular morphology in diseases of the ocular surface. PMID- 3101020 TI - Electroretinographic findings in the mucopolysaccharidoses. AB - The degree of retinal involvement of 20 patients (ages 3-21) with mucopolysaccharidosis (MPS) types I, II, and III was assessed using electroretinography (ERG) under standardized conditions. ERG evidence of retinal dysfunction ranged from none to severe in MPS I and II, and from moderate to severe in MPS III. The ERG abnormalities were common to all three types of MPS, and showed the pattern seen in rod-cone degenerations, where the rod-mediated responses are more severely affected than the cone-mediated responses. The ophthalmoscopic signs were less striking than the electrophysiologic findings, and were usually restricted to mild changes of the retinal pigment epithelium. PMID- 3101021 TI - An alternative method of grading diabetic retinopathy. AB - The purpose of this report is to present a system for grading the severity of diabetic retinopathy that is a rapid, relatively inexpensive, and standardized alternative to the more detailed Early Treatment Diabetic Retinopathy Study (ETDRS) system; present data on its reproducibility; and compare it to the detailed ETDRS grading system. The alternative system was used to grade fundus photographs obtained during a large prevalence study, the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). The alternative method involved grading seven stereoscopic standard fields as a whole, and assigning a level of severity for the eye according to the greatest degree of retinopathy using a modified Airlie House Classification scheme. Using an eight-level classification system of increasing severity of retinopathy, there was 78.3% exact agreement between the alternative and ETDRS systems. A grader regraded all 503 disagreements, and was in exact agreement 49.3% of the time with the alternative system, 35.7% of the time with the detailed system, and 15.0% with neither the alternative or detailed systems. Interobserver agreement for the alternative system was 78.5%; intraobserver agreement over a 9 month to 1 year period was 90.0% for grader 1 and 84.0% for grader 2. The alternative system of grading, when used by experienced graders, is a reproducible method for objectively determining retinopathy status in epidemiologic studies. PMID- 3101023 TI - Responsibilities for quality assurance in prehospital care. PMID- 3101022 TI - Necrobiotic xanthogranuloma with paraproteinemia. Case report and a pathogenetic theory. AB - Necrobiotic xanthogranuloma with paraproteinemia is a clinical and histopathological entity characterized by xanthelasma-like lesions in the periorbital region and elsewhere, paraproteinemia, leukopenia, and an elevated erythrocyte sedimentation rate. Multiple myeloma has been reported as an accompanying feature in several cases. We examined a patient with necrobiotic xanthogranuloma and multiple myeloma in whom an IgG kappa monoclonal protein was identified in serum, urine, bone marrow, and bilateral periorbital lesions. We speculate that increased serum immunoglobulins complexed with lipid may be deposited in the skin, leading to a foreign body giant cell reaction and the subsequent characteristic histopathologic features of necrobiotic xanthogranuloma. PMID- 3101024 TI - The challenge of providing quality psychiatric services in a rural setting. AB - The development of a system of services that addresses the medical, psychiatric, and social needs of mentally ill persons may be particularly difficult in rural health areas because of environmental, sociocultural, and program issues different from those in urban settings. The quality of rural mental health care must be evaluated in light of these unique needs and resources. This article identifies and discusses problems in delivery of services, including environment, denial, confidentiality, costs, and human resources, and outlines responses to these problems seen as challenges rather than as barriers. PMID- 3101025 TI - Analyzing patient time in the emergency department. AB - Inefficiency in hospital emergency departments (EDs), reflected by unduly long patient visits, threatens patient care quality and hospital public relations. To assess its situation with regard to this problem, the University Medical Center at the Arizona Health Sciences Center (Tucson) analyzed ED visits according to time spent in triage, in the examination/treatment room, and awaiting discharge. Patient acuity, laboratory and radiology procedures, consultations, and arrangements for inpatient admission were taken into account. Findings led to corrective actions to increase efficiency and laid the groundwork for further studies. PMID- 3101027 TI - Hospital compliance with Joint Commission standards: findings from 1984 surveys. PMID- 3101026 TI - Quality assurance as part of program evaluation: guidelines for managers and clinical department heads. PMID- 3101028 TI - Collective self-evaluation in a surgical department. AB - Since 1978, the vascular and endocrine surgery section at the Henri Mondor University Hospital Center, near Paris, has regularly evaluated the quality of its work by process of collective self-evaluation--self-evaluation because no one from outside the section participates, and collective because everyone contributing to the results of surgery does participate. This article describes the collective self-evaluation process, including the goals, methods, and results of the various types of evaluation involved. It also discusses the impact of the process, barriers to optimal efficiency, and conditions for success. PMID- 3101029 TI - Evaluating improvements in multistaged health care: the risk-care-outcome cycle. AB - A new method of program evaluation was developed in Israel to assess the impact of improved care on the health of mothers and infants. Care before conception and during the prenatal, intrapartum, and postpartum periods form an interrelated sequence. The method, therefore, evaluates the interplay among risks, health care quality improvements, and outcomes within each stage of care, and measures the impact of improved outcomes on subsequent stages. The expansion or modification of pilot maternal and infant health efforts in 42 Israeli communities will be based on the results of this evaluative effort. The concepts employed in this assessment are applicable in many other situations that involve sequences of health services (eg, preoperative, operative, and postoperative care) where the success of each phase of care affects the risks of the succeeding stage. PMID- 3101030 TI - Genetic influence on the antibody response to antigens of Schistosoma mansoni in chronically infected mice. AB - Immunoprecipitations of in vitro translation products of mRNA from adult Schistosoma mansoni worms with sera from chronically infected mice of 12 inbred strains reveal a strain-dependent heterogeneity in the antibody responses to schistosome antigens. Of the strains tested the response to the 86K antigen was restricted to mice of haplotypes H-2d H-2k, and H-2a while the 14K antigen was only recognized by H-2k mice. Responses to other antigens revealed the influence of non-H-2 genes on the antibody response although no clear correlation was apparent between the antigens recognized and the non-H-2 genes of the strains. Both dominant and recessive responses towards individual antigens were seen in F1 animals. Some of these results support the cross tolerance model of Ir gene function. PMID- 3101031 TI - Schistosoma mansoni egg antigens: preparation of rabbit antisera with monospecific immunoprecipitating activity, and their use in antigen characterization. AB - A simple method for producing monospecific rabbit antisera, applied originally to the constituents of human serum (Goudie et al. 1966), has been adapted for use with Schistosoma mansoni egg antigens. Replicate isolated immunoprecipitin arcs resulting from the immunoelectrophoretic reaction between an egg antigen and a polyspecific antiserum were excised, washed extensively to remove non precipitated contaminants, homogenized, and emulsified with complete Freund's adjuvant. Rabbits were given weekly subcutaneous injections of the emulsion in multiple sites, and a monospecific precipitating antibody against the respective immunizing antigen generally resulted within 6 weeks of the commencement of immunization. Antisera raised in this manner against S. mansoni egg antigens omega 1, alpha 1 and kappa 5 have been used to characterize the antigen with respect to their stage- and species-specificity. After immunoabsorption to remove background activity, the sera could be used to detect unequivocally the respective antigens in crude egg homogenate that had been subjected to SDS-PAGE and electrotransfer to nitrocellulose paper. PMID- 3101032 TI - Spleen and lymph node cell populations, in vitro cell proliferation and interferon-gamma production during the primary immune response to Toxoplasma gondii. AB - An animal model for the study of transient lymphadenopathy-splenomegaly during toxoplasmosis is presented. Injection of CBA/J mice with the low virulent, cyst forming strain of Toxoplasma gondii (Pe strain) induces a three to four fold increase in weight and cellularity of spleen and lymph nodes with peak changes at 30-50 days after infection. The spleen displays marked haemopoiesis, a 30 fold increase in mononuclear phagocytes, and a two fold increase in Lyt2+ lymphocytes. Lymph nodes show a five fold increase in mononuclear phagocytes and a four and a half fold increase in Lyt2+ T cells. The increase in mononuclear phagocytes significantly alters T cell/macrophage ratios and this is associated with decreases in in vitro cell proliferation to mitogen and toxoplasma antigen. The relationship between alterations in cell balance of mononuclear phagocytes and T cell subsets and the expression of transient immune dysfunction can now be examined by modulating changes in these cell types. PMID- 3101033 TI - Specific suppression of delayed hypersensitivity expression to Trypanosoma cruzi in mice. AB - The absence of cutaneous delayed type hypersensitivity (DTH) expression was investigated in Trypanosoma cruzi infected mice. Neither spleen cells nor peritoneal exudate cells from infected mice transferred DTH to normal recipients in local or systemic adoptive transfer experiments. Expression of DTH in T. cruzi immunized mice was suppressed specifically by Thy-1 negative spleen cells from acutely and subacutely infected animals. Suppression was observed only upon systemic transfer, but not when infected mice spleen cells were added to DTH effector cells and transferred to normal recipients. These results suggest that cutaneous DTH expression in acutely infected mice, might be blocked by mechanisms other than those described for suppression of lymphocyte proliferation and of DTH induction to T. cruzi. PMID- 3101034 TI - [Streptococcus faecalis: sensitivity to quinolones, penicillins and aminoglycosides alone or in combination]. AB - Isolates of Streptococcus faecalis are moderately susceptible to quinolones, penicillins and aminoglycosides used alone. Penicillin-aminoglycosides synergism is not observed against aminoglycosides high-level resistant strains. The combination of an aminoglycoside plus a quinolone was synergistic against susceptible strains of S. faecalis but not against aminoglycosides high-level resistant strains. No antagonistic effect of quinolones plus aminoglycosides or plus penicillin was observed. PMID- 3101035 TI - Intensive care unit resources and costs. PMID- 3101036 TI - [Visual seizures and benign epilepsy in children with paroxysmal occipital discharges]. AB - The study of ocular symptoms during seizures and of electroencephalograms between seizures in 244 children affected by partial epilepsy has allowed the isolation of nine cases of benign epilepsy with occipital paroxysms. Ocular symptoms as well as other accompanying symptomatology are detailed. The diagnostic procedure should address secondary occipital epilepsy and migraine with ocular symptoms. PMID- 3101037 TI - [Thrombocytosis and reduced levels of factor VIII in rheumatoid purpura in children]. AB - Thirty three patients with Henoch-Schoenlein purpura were studied at various developmental stages of this disease: specially platelet counts and factors XIII and VIII. During the development phases: 40,6% of the patients have a slight but regressive thrombocytosis (greater than 400 G/l); and 75% a reduced factor XIII, well correlated with the severity of the clinical status (level as low as 60% can be considered as a "gravity threshold"), and corrected during the improvement of the disease. This reduced factor XIII is probably linked to the local inflammation in the vessels. Factor VIII studies (specially VIII A: Ag) were normal. PMID- 3101038 TI - Stability after freezing and thawing of solutions of mitomycin C in plastic minibags for intravesical use. AB - Solutions of 0.6 mg/ml mitomycin C (Mutamycin) in NaCl solution 0.9% in plastic minibags for intravesical use were stored at -20 degrees C and -30 degrees C and thawed by microwave radiation. Both unbuffered solutions and solutions buffered to approximately pH 7.5 were investigated. Concentrations were measured with HPLC. During freezing and storage at -20 degrees C sometimes crystallization of mitomycin C occurred. However, both buffered and unbuffered solutions could be frozen at -30 degrees C during at least four weeks and subsequently thawed without loss of content. Unbuffered mitomycin C solutions could be refrozen at 30 degrees C for another four weeks. Also buffered and unbuffered solutions of another brand of mitomycin C (Mitomycin-C Kyowa) could be frozen at -30 degrees C during four weeks without significant deterioration. PMID- 3101039 TI - Breakpoint distribution in variant Philadelphia translocations in chronic myeloid leukemia. AB - A statistical analysis of the 327 cases of variant Philadelphia chromosome so far reported in chronic myeloid leukemia was performed. The results showed 28 bands to be significantly rearranged; 11 bands are known to contain a fragile site; 12 are included in the smallest region of overlap of 14 proto-oncogenes. Also, 23 bands are known to be significantly involved in structural rearrangements in other malignancies. PMID- 3101041 TI - Total parenteral nutrition. PMID- 3101040 TI - The dynamics of chromatin carcinogen interactions in the human cell. AB - Human lung epithelioid cells were treated with Benzo (a) pyrene diol epoxide (anti) in order to establish the binding and removal of covalent adducts in chromosomal components. Isolating two different classes of mononucleosomes, it was found that their DNA contained different concentrations of B(a)PDE-DNA adducts, while in both these mononucleosomal preparations only histones H2A and H3 contained detectable amounts of the carcinogen. Further analysis showed that in the intact human cell the carcinogen-DNA adduct distribution is constantly changing as a function of differential accessibility and repair. These results emphasize the dynamics of chromatin-carcinogen modifications. PMID- 3101042 TI - Nursing assessment of symptoms associated with hyperviscosity syndrome. PMID- 3101043 TI - [Characteristics of patients--chronic carriers of Mycobacterium tuberculosis in Poland 1984]. PMID- 3101044 TI - [Retrocoronal radiography (bite-wing)]. PMID- 3101045 TI - [Periodontal maintenance therapy]. PMID- 3101046 TI - [Cements and impression materials (preparation and spatulation)]. PMID- 3101047 TI - [Operational procedures: significance and methods]. PMID- 3101048 TI - [Raynaud's disease]. PMID- 3101049 TI - [Not all sugar is harmful]. PMID- 3101051 TI - More on cardiac pacing. PMID- 3101050 TI - [Dental fluorosis: recent findings and historical review]. PMID- 3101052 TI - Digitalis for congestive heart disease in the elderly. A family practice view of the efficacy of long-term therapy. AB - The long-term efficacy of digoxin maintenance therapy must be determined individually for patients with normal sinus rhythm who have a history of congestive heart failure but no remaining signs or symptoms. Predictive factors for successful discontinuation of the agent in the elderly include normal mental status (including absence of depression), ability to adequately perform activities of daily living, general feelings of well-being, absence of multiple organic disease, absence of multiple drug use, and no evidence of existing congestive heart failure or atrial fibrillation. Our findings indicate that physicians and patients need to reexamine the concept that congestive heart failure is necessarily a chronic disease. Certainly, evidence exists that continuing digitalis therapy indefinitely is inappropriate and may be harmful. Further investigation may prove that congestive heart failure in the elderly, like pneumonia, is a common acute occurrence and in many cases not a chronic state for which patients are destined to receive medication indefinitely. We hope that the findings from our small sample will stimulate other investigators to question the indiscriminate long-term use of digitalis in the elderly. PMID- 3101053 TI - Male infertility. 3. Endocrine causes. AB - Endocrine causes of male infertility range from easily manageable disorders such as hypothyroidism to complex problems such as pituitary tumors. Proper management requires a thorough understanding of the hypothalamic-pituitary-testicular axis. Hormonal evaluation is performed only when the patient's history and results of physical examination indicate an endocrine problem. With proper identification and treatment, most of these problems can be successfully managed. PMID- 3101054 TI - Transient lupus anticoagulant and fansidar therapy. AB - A case of the Stevens-Johnson syndrome following Fansidar therapy is reported in which a marked feature was the presence of a circulating anticoagulant of the lupus inhibitor type. Treatment with steroids resulted in complete recovery and disappearance of the anticoagulant. PMID- 3101055 TI - Ultrastructural immunolabeling in the diagnosis of light-chain-related renal disease. AB - Renal tissue from eight patients with light-chain deposition disease (LCDD) was immunolabeled for electron microscopy by a postembedding indirect immunogold staining procedure, using anti-kappa and anti-lambda antibodies. This technique provided an exact immunomorphological method to confirm the presence of monotypical light chains in glomeruli, tubules, and vessels. In two cases, it served to prove monotypical light-chain deposition which was not clear upon examination of sections stained for kappa and lambda light chains at the light microscopic level, using PAP or immunofluorescence methods. Three cases of amyloid nephropathy, in which the amyloid deposits stained for monospecific light chains and were immunolabeled ultrastructurally, are also described. LCDD manifests with a variety of morphological patterns in the kidney and the pathological definition of this entity has been difficult. Ultrastructural immunolabeling is a useful method to supplement existing techniques in the diagnosis of LCDD and related conditions. One outstanding feature of the postembedding technique is the ability to examine fixed and preserved renal tissue for the presence of light chains on a retrospective basis. PMID- 3101056 TI - [Long-term oxygen therapy at home--technical aspects of oxygen production, administration and acceptance by patients with chronic respiratory insufficiency]. PMID- 3101057 TI - A simple purification of calmodulin by reversed phase chromatography with hydrophobic polymer 3520. AB - A new adsorption chromatography procedure for the purification of calmodulin from bovine brain was developed using polymeric adsorbent 3520. Calmodulin was first isolated by DEAE-Cellulose column chromatography and further purified to apparent homogeneity following elution with 50% ethanol from the adsorbent column. Polyacrylamide gel electrophoresis showed one band either in the presence of Ca2+ or EGTA. The polymeric adsorbent 3520 is a non-polar polymer lacking exchangeable groups. The selective adsorption of calmodulin is based on hydrophobic interaction within the matrix, and is Ca2+ independent. Neither high salt (0.5 M NaC1) nor EGTA (5 mM) was able to elute the CaM from the adsorption column whereas ethanol (50%) eluted it completely. This method is simple to use and it provides highly purified calmodulin with high yield. PMID- 3101058 TI - Affinity chromatography of beta-glucosidase and endo-beta-glucanase from Aspergillus niger on concanavalin A-Sepharose: implications for cellulase component purification and immobilization. AB - Affinity chromatography of a commercial preparation of beta-glucosidase from Aspergillus niger using concanavalin A-Sepharose (CAS) was employed as a means of purifying this glycoprotein. However, mannose (up to 1.08 M) was ineffective as an eluent of this enzyme from CAS, as were several other sugars and their derivatives, including 0.5 M glucose. Also, washing the CAS: beta-glucosidase complex with buffer at pH 3.5 in the absence of MnCl2 and CaCl2 (required to preserve the binding activity of concanavalin A below pH 5.0) did not result in elution of this enzyme. On the contrary, endoglucanase activity present in a crude cellulase complex (A. niger) which bound to CAS could be eluted by mannose (0.5-0.7 M) and was fractionated into at least two components. The CAS: beta glucosidase complex hydrolyzed cellobiose to glucose and possessed an activity of 2,158 units/g dry CAS. It could be used, therefore, for continuous cellobiose hydrolysis without leakage of enzyme from the support. PMID- 3101059 TI - [Effect of thermal treatment on the structure and biological properties of tuberculin]. AB - The effect of heat treatment used in the course of tuberculin production by Mycobacteria tuberculosis cells on the structure and biological activity of tuberculin was studied. Methods of preparative and analytical gel-filtration were used. The largest quantity of the biologically active component was obtained after 2-hour heat treatment of the mycobacteria culture. PMID- 3101060 TI - [Effect of the combined action of laser irradiation and an alternating magnetic field on the multiplication of Mycobacterium tuberculosis]. PMID- 3101061 TI - Reptiles as intermediate and/or final hosts of Sarcosporidia. AB - A revision of the parasitic protozoan genus Sarcocystis which has reptiles as intermediate and/or final hosts is given. Twelve species described as having reptiles as intermediate hosts are considered valid species of the genus Sarcocystis. Snakes have been shown experimentally to be the final hosts of ten other Sarcocystis species which have rodents as their intermediate hosts. One species, S. podarcicolubris, has poikilothermic intermediate and final hosts. Classification of a new Sarcocystis species based either on scantily described cysts or only on sporulated oocysts or sporocysts from feces is not sufficient and cannot be justified. A new species should be recognised only after experimental retransmission and/or because of unequivocal morphological characteristics of the sarcocyst. PMID- 3101062 TI - Experimental transmission of Sarcocystis muriviperae n. sp. to laboratory mice by sporocysts from the Palestinian viper (Vipera palaestinae): a light and electron microscope study. AB - Sporocysts collected from the feces of a Palestinian viper (Vipera palaestinae) were administered orally to species of various rodent genera such as Mus, Microtus, Mastomys, Meriones and Oryctolagus. Infections developed only in laboratory mice (Mus musculus). This investigation established the life cycle of Sarcocystis muriviperae in the laboratory. S. muriviperae is described as a new species, based on light and electron microscopic observations and repeated transmission studies. Naturally and experimentally infected Palestinian vipers both excreted structurally identical sporocysts measuring 9.6 micron (8.8-10.5 microns) by 12.2 microns (11.7-12.9 microns). Sporulation inside the snakes' intestine is completed between 14 and 19 days post-inoculation (p.i.). Rosette like schizogonic stages were found in the liver cells of laboratory mice 9-10 days after infection with sporulated sporocysts. Sarcocysts measured up to 1,000 microns in length on day 36 p.i. and were mainly filled with metrocytes. The septated sarcocysts found 136 or 165 days p.i. reached a length of 5-8 mm and a width of 150-400 microns. The primary sarcocyst wall formed cauliflower-like branched protrusions about 3.5 microns in length. PMID- 3101063 TI - In vitro cultivation of Herpetosoma trypanosomes in insect cell tissue culture media. AB - The cultivation of Herpetosoma trypanosomes in insect tissue culture media supplemented with foetal calf serum is described. Trypanosoma lewisi and T. musculi, which can be grown in blood agar media, were compared with four other species of Herpetosoma trypanosomes, T. microti, T. evotomys, T. grosi and T. nabiasi, in their growth in Schneider's Drosophila medium, Grace's, Mitsuhashi Maramorosch, RPMI 1640, TCM 199 and nutrient blood agar media. Schneider's Drosophila and Grace's media supplemented with 20% foetal calf serum proved the most suitable media for growth of all parasites except T. nabiasi from rabbits which was not successfully established. Primary cultures were passaged after approximately 3 weeks and were maintained to continuously produce metacyclic trypomastigotes which produced less virulent infections although they maintained their infectivity to their respective hosts. The growth patterns in culture and morphology of the parasites are described. PMID- 3101064 TI - Replacement of lysine residue 1030 in the putative ATP-binding region of the insulin receptor abolishes insulin- and antibody-stimulated glucose uptake and receptor kinase activity. AB - To test whether the tyrosine kinase activity of the insulin receptor is crucial for insulin action, we have constructed mutations of the human insulin receptor at Lys-1030, which is in the presumed ATP-binding region. By using oligonucleotide-directed mutagenesis, this lysine residue was replaced with either methionine, arginine, or alanine. Chinese hamster ovary cells were transfected by mutant cDNAs and the expressed insulin receptors were characterized. We show here that none of these mutants exhibited insulin activated autophosphorylation and kinase activity in vitro. They also do not mediate insulin- and antibody-stimulated uptake of 2-deoxyglucose. The tyrosine kinase activity is thus required for a key physiological response of insulin. PMID- 3101066 TI - Evaluation of the in vitro production of interferon gamma and other lymphokines in uremic patients. AB - It has been suggested that a deficient immune response can be responsible at least partially for the high risk of infections and neoplasia in uremic patients. Since interferon (IFN) is critical to the immune response, we have evaluated the in vitro production of IFN-gamma and other lymphokines by peripheral blood mononuclear cells (PBMC) drawn from patients with end-stage renal disease and appropriate controls. We have correlated production of lymphokines by these cells with proliferative response to different mitogens. It was found that the secretion of IFN-gamma in response to all three mitogens was elevated in these patients compared with the control group. This elevation was significant with both phytohemagglutin and staphylococcal enterotoxin A, but not with Con A. No significant difference was observed in production of lymphotoxins, IL-2, and leukocyte migration inhibition responses. In contrast the proliferative response appeared diminished in the PBMC of uremic patients. We concluded that defective lymphokine generation is not a major immunological problem in patients with end stage renal disease. Indeed, they appear to release excess amount of IFN-gamma which is known to be a macrophage-activating factor. It is suggested that high IFN-gamma activity could enhance the secretion of IL-1 or endogenous pyrogen and result in development of febrile reactions in dialysis patients. PMID- 3101065 TI - Recovery from anti-VIII:C (antihemophilic factor) autoimmune disease is dependent on generation of antiidiotypes against anti-VIII:C autoantibodies. AB - Plasma samples obtained from a patient 6 wk, 6 months, and 4 yr after recovery from anti-VIII:C (anti-hemophilic factor, where VIII:C = factor VIII procoagulant activity) autoimmune disease were found to contain antibodies that inhibited anti VIII:C activity in the patient's prerecovery plasma and in the plasma of two other patients with anti-VIII:C autoantibodies. F(ab')2 fragments from postrecovery IgG suppressed anti-VIII:C activity in F(ab')2 fragments from prerecovery IgG within a narrow range of molar ratios. Anti-VIII:C activity in F(ab')2 autoantibodies was also inhibited by F(ab')2 fragments from polyspecific therapeutic immunoglobulins prepared from a large pool of normal donors (IVIg). IgG from prerecovery plasma bound to F(ab')2 from postrecovery IgG and to F(ab')2 from IVIg, as assessed by ELISA. Affinity chromatography experiments demonstrated that F(ab')2 from postrecovery IgG preferentially bound anti-VIII:C antibodies among F(ab')2 fragments from prerecovery plasma containing anti-VIII:C autoantibodies. F(ab')2 from prerecovery plasma bound in higher amounts to postrecovery F(ab')2 than to IVIg. Insolubilized F(ab')2 fragments from postrecovery plasma also bound F(ab')2 fragments prepared from the plasma of another patient with anti-VIII:C autoimmune disease, although in lesser amounts than the patient's own prerecovery anti-VIII:C F(ab')2 antibodies. These observations suggest that human anti-VIII:C autoantibodies share idiotypic determinants and that spontaneous recovery from anti-VIII:C autoimmune disease occurs through idiotypic suppression of autoantibodies. In patients who recover from autoimmune disease and in patients in whom autoantibodies have been suppressed by infusions of IVIg, antiidiotypic antibodies, possibly by providing internal images of the antigen, may have shifted the immune system toward the steady-state equilibrium that prevents autoimmunity in normal individuals. PMID- 3101067 TI - Effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS) on catecholamine levels in plasma and cerebrospinal fluid (CSF) in anesthetized rats. AB - The effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS) on norepinephrine (NE) levels in plasma and CSF was examined in urethane-anesthetized rats. Intravenous injection of L-DOPS (0.5, 1, and 10 mg/100 g body wt) raised plasma NE levels in a dose-related manner whereas CSF NE levels were significantly increased only by the largest dose of L-DOPS. Intracerebroventricular injection of L-DOPS (50 and 250 micrograms/rat) dose-relatedly raised CSF NE levels whereas plasma NE levels were slightly increased by a larger dose of L-DOPS. These findings may indicate that L-DOPS stimulates central noradrenergic mechanisms in the rat although a large dose of L-DOPS is required for peripheral administration. PMID- 3101068 TI - Hormone secretion by euthyroid and hypothyroid rat ovaries during the early stages of hCG-induced ovarian cyst development. AB - This study was undertaken to examine ovarian steroid production during the early stages of hCG-induced ovarian cyst formation in the hypothyroid rat. Rats were placed into two groups with one group made hypothyroid by adding thiouracil to their diet. After 10 days, each group was divided into two subgroups with one subgroup receiving daily injections of hCG for 2 days and the other subgroup receiving saline. On the morning of Day 13, ovaries were removed and incubated for 2 hr. No significant difference in progesterone secretion was observed. However, ovaries from hypothyroid, hCG-treated rats secreted significantly more testosterone and estradiol than ovaries from vehicle-treated, hypothyroid rats and euthyroid, hCG-treated rats. In a second experiment, ovaries from euthyroid and hypothyroid rats treated with hCG were incubated in medium supplemented with 100 nM androstenedione and 0 or 100 ng FSH/ml. FSH failed to affect progesterone, testosterone, and estradiol secretions by ovaries from euthyroid, hCG-treated rats. In contrast, FSH significantly enhanced testosterone and estradiol secretion by ovaries from hypothyroid, hCG-treated rats. These results support the hypothesis that increased levels of testosterone and estradiol secretion have a central role in the induction of polycystic ovaries by hCG in the hypothyroid rat. PMID- 3101069 TI - Antibodies to saline extractable tissue antigen in sera of patients with renal diseases. AB - Multiple serum samples originating from 110 renal allograft recipients were examined against saline extract of normal human kidney by means of double diffusion gel precipitation. Eleven recipients were found to be positive; 99 of 106 sera from these patients were positive. Pretransplantation sera were available from 7 of these recipients and 6 patients were found "positive." The precipitation reaction was composed of one line. Identity reactions were formed between the lines produced by sera from all patients except 1. Sera of patients from end-stage renal disease produced similar reaction; however, only 3 of 234 sera from patients with nonrenal diseases precipitated the kidney extract. None of 154 normal sera were positive. Several positive sera also were positive in complement fixation tests with human kidney extract. Evidence was presented that the antibodies under study combined with a nonorgan-specific but species restricted tissue antigen. The hypothesis was advanced that these antibodies are autoantibodies formed in response to a sequestered antigen released as a result of tissue damage. Apparently, the antigen is released frequently in immunogenic form from injury to kidney but infrequently from injury to other organs. PMID- 3101070 TI - Overcoming mitomycin C resistance with semisynthetic derivatives. PMID- 3101071 TI - Two distinct events in lineage establishment of a biopotential hemopoietic cell line. AB - HL-60, a human myelomonocytic cell line can be induced to differentiate along either granulocyte or monocyte pathways and therefore is a good model to study lineage establishment. We have shown that there are two classes of reactions in the establishment of the granulocytic line distinguishable by their kinetics. The fast reaction occurs in hours and is induced by ouabain or A23187, agents which effect ions. The slow reactions occur at a constant rate over a period of 5 days and are induced by the surrogate inducers RA and D3 but also by the natural inducer GM-CSF. GM-CSF induces the enzyme markers which we use to characterize both granulocytes and monocytes in the same cell. If these markers are indeed unique to each of the lines this means that HL-60 has both gene programs initiated by GM-CSF and D3. Variant lines which do not respond to one or more of the inducers can be used to analyze this point since variants which are induced only to granulocytes or only to monocytes by GM-CSF have been isolated. PMID- 3101072 TI - The influence of a new prostaglandin E2 analogue (FCE 20700) on gastric acid and pepsin secretion in the dog. AB - The effects of FCE 20700, a new prostaglandin E2 analogue, on gastric acid and pepsin secretion stimulated by different secretagogues were studied in dogs. Intravenous FCE 20700 produced a significant inhibition of total acid output (TAO) induced by pentagastrin or histamine in gastric fistula (GF) dogs. This effect was short-lasting and mainly due to a reduction in the volume of gastric juice with little acid concentration change. TAO and pepsin output stimulated by 2-deoxy-D-glucose were similarly inhibited by intravenous FCE 20700. In dogs chronically fitted with both GF and Heidenhain pouch (HP), intragastric FCE 20700 significantly inhibited TAO stimulated by pentagastrin or histamine from HP, while acid secretion from GF was not significantly affected. It is concluded that FCE 20700 possesses a weak antisecretory activity in dogs. Consequently the antiulcer effects of this prostaglandin derivative seem to be largely independent from its influence on gastric acid and pepsin secretion. PMID- 3101073 TI - Exposure to amphetamine after substantia nigra lesion interferes with the process of behavioral recovery. AB - Recovery from unilateral substantia nigra lesion may be indicated by re-emergence of circling in the pre-lesion preferred direction. Following 6-OHDA-induced lesion of the dominant SN, we examined: (a) The effect of the delay from lesioning on amphetamine-induced rotation asymmetry, and (b) The effect of early post-lesion exposure to amphetamine on later rotation asymmetry. d-Amphetamine was initially injected either 7, 14, 21, or 30 days after lesioning. Transient circling in pre-lesion preferred direction (contralateral to lesioned side) was more frequently encountered on days 7 and 30 after lesioning, as compared to days 14 and 21. The contralateral rotation observed on day 7 is attributed to degeneration-induced DA release, whereas contralateral rotation noted on day 30 is believed to reflect the operation of post-lesion compensatory processes within the spared DA neurons. In response to subsequent amphetamine administration 30 days after lesioning, rats with previous exposure to the drug circled ipsilaterally, whereas most rats given amphetamine for the first time in that session rotated contralaterally to the lesion. These findings suggest that post lesion administration of amphetamine interferes with the process of recovery. PMID- 3101074 TI - Inhibitory action of hydralazine on catecholamine secretion from cultured bovine adrenal chromaffin cells. AB - Hydralazine caused a concentration-dependent inhibition of the secretion of catecholamines induced by carbamylcholine or high K+ from cultured bovine adrenal chromaffin cells, and also caused the significant inhibition of radioactive calcium uptake induced by carbamylcholine into the cells. However, hydralazine failed to inhibit the secretion of catecholamines evoked by the calcium ionophore, A23187. The inhibitory action of hydralazine on catecholamine secretion induced by carbamylcholine was not affected by increasing the concentration of calcium ion in the reaction mixture. These observations therefore seem to indicate that the inhibitory action of hydralazine is not due to either the blocking of receptors for carbamylcholine or the disruption of the secretory machinery, and suggest that the drug may cause the inhibition of catecholamine secretion through its blocking action on calcium influx into the cells. PMID- 3101075 TI - Metabolic response of polymorphonuclear leukocyte to arachidonic and linoleic acids. AB - Various stimuli act on polymorphonuclear leukocytes (PMN), activating membrane bound phospholipase A2 and C, and diglyceride lipase and then liberating unsaturated fatty acids (USFAs). These liberated USFAs are immediately metabolized through various metabolic pathways such as cyclooxygenase, lipoxygenase, phosphatidylinositol metabolism etc. It is possible that the metabolic intermediates of these pathways reveal various physiological actions. This work was undertaken to clarify whether stimuli on PMN depend on these USFAs themselves or on their oxidation products. The following results were obtained: 1. USFAs such as arachidonate and linoleate stimulate PMN, accelerating superoxide (O2) generation, depolarization of membrane potential and increase in [Ca2+]i. 2. Oxidation products of USFAs have no stimulative effect on PMN. The decrease in the stimulative effect of these USFAs following their oxidation is proportional to the quantitative decrease in non-oxidized linoleate. 3. USFAs accelerate membrane permeability of Ca2+, and their oxidation products enhance non-specific membrane permeability in proportion to the formation of monohydroxy compound. These results suggest that stimulative effects of USFAs on PMN do not depend on their oxidation products but on unoxidized fatty acids. Furthermore, among the oxidation products of the USFAs, monohydroxy compound acts as a strong perturber of membrane and accelerates membrane permeability. PMID- 3101076 TI - Dispersal of a plasmid-borne chloramphenicol resistance gene in streptococcal and enterococcal plasmids. AB - Plasmids coding for chloramphenicol resistance, five isolated from streptococci of groups A, B, and G, ten from enterococci (Enterococcus faecalis, Enterococcus faecium), and two from staphylococci, were tested for sequence homology with the chloramphenicol resistance gene of pIP501, a 30-kb plasmid originally isolated from a group B Streptococcus. The 6.3-kb HindIII fragment of pIP501, known to carry the chloramphenicol resistance gene, was cloned into pBR322. A 1.6-kb portion of the cloned fragment, which included most of the chloramphenicol resistance gene, was used as probe in DNA-DNA hybridization experiments. Sequence homology was detected between the probe and four of the streptococcal, seven of the enterococcal, and one of the staphylococcal plasmids. The absence of hybridization between this probe and one plasmid isolated from a group B Streptococcus, as well as three isolated from E. faecalis, indicated that there are at least two different plasmid-borne chloramphenicol resistance determinants in the streptococci and in the enterococci. PMID- 3101077 TI - [The classification of endogenous psychoses]. PMID- 3101078 TI - [The recessive inheritance of affective paraphrenia (the incidence in consanguineous marriages)]. PMID- 3101079 TI - [The classification of endogenous psychoses before Wernicke, Kleist and Leonhard]. PMID- 3101080 TI - [Can schizophrenias be clinically and etiologically separated?]. PMID- 3101081 TI - [Thoughts on the pathogenetic and phenomenologic separation of the endogenous psychosyndrome]. PMID- 3101082 TI - [Cycloid psychoses and their status within the scope of the classification of endogenous psychoses]. PMID- 3101083 TI - [Cycloid and schizoaffective psychoses in a study of schizophrenia in Bonn]. PMID- 3101084 TI - [Leonhard's affective paraphrenia from the viewpoint of the Vienna school]. PMID- 3101085 TI - An intrinsic way of multiclassification of endogenous psychoses. A follow-through investigation/Budapest 2000/based upon Leonhard's classification. PMID- 3101086 TI - The genetical basis of the Leonhardian classification of endogenous psychoses. PMID- 3101087 TI - [Value of "suture bones" in the diagnosis of minor brain damage in early childhood]. AB - In a sample of 278 children with normal intelligence and behaviour disorders the x-rays of the craniums were analysed especially on the aspect of suture bones. They were related to the clinical total diagnosis "Minimal Brain Damage". Statistically significant relations between the appearance of suture-bones and other cranium anomalies as well as between clinical total diagnosis "MBD" were to be found. So the results by D. Muller on the clinical value of suture-bones are supported. PMID- 3101088 TI - [Neurocutaneous syndrome with a ventricular tumor]. AB - It is reported on a 19 year-old female patient with a mild mental retardation and a neurocutaneous syndrome. A tumour of a lateral ventricle had caused a partial blockade of the Foramen of Monro without symptoms of brain pressure. The patient shows lesions on the skin corresponding to a neurofibromatosis. Neurologically there was a choreatic syndrome, which can occur in transitional forms from neurofibromatosis to tuberous sclerosis (TS) of the brain. Psychologically a psychorganic syndrome, typical for TS, with disturbances of affectivity and motive developed. There was no essential improvement of the neurological and psychical symptoms by surgical removal of the brain tumour nor were there changes in the EEG except for an acceleration of the basic rhythm. PMID- 3101089 TI - Problems to anticipate in treating difficult patients in a long-term psychiatric hospital. AB - In a previous report, the authors identified four dimensions of patient pathology associated with treatment difficulty: withdrawn psychoticism, character pathology, violence-agitation and suicidal-depressed behavior. In a subsequent study, they linked these dimensions to patterns of countertransference. The present research extends the two prior reports by examining the relations of the patient pathology dimensions to staff members' dissatisfaction with four areas of treatment: interpersonal approaches, structure and control, quality of teamwork, and medication. The major findings are: withdrawn psychoticism primarily relates to dissatisfaction with interpersonal treatment approaches; character pathology entails dissatisfaction with the level of structure and control; violence agitation poses particular problems for teamwork; and suicidal-depressed behavior is unrelated to dissatisfaction with any dimension of treatment. The authors propose that these various problems in treatment are, in part, mediated by patterns of countertransference which they described in the prior paper. These findings should help staff members to focus their attention on areas of treatment in which problems are bound to arise in work with different types of difficult patients. PMID- 3101090 TI - Symposium. Psychoanalytic phenomenology: the work of Stolorow and Atwood. I. Blowing metaclouds away. PMID- 3101091 TI - Symposium. Psychoanalytic phenomenology: the work of Stolorow and Atwood. II. Clinical theory and metapsychology: incompatible or complementary? PMID- 3101092 TI - Symposium. Psychoanalytic phenomenology: the work of Stolorow and Atwood. III. Psychoanalysis and phenomenology: a new synthesis. PMID- 3101093 TI - Symposium. Psychoanalytic phenomenology: the work of Stolorow and Atwood. IV. Reply to R. White, M. Basch and M. Nissim-Sabat. PMID- 3101094 TI - The ethical unconscious. PMID- 3101095 TI - Addressing the oedipal dilemma in Macbeth. AB - Macbeth has been viewed as a play about the oedipal crime of patricide. This paper elaborates on this approach by elucidating the oedipal and preoedipal themes in the roles played by women in the drama, particularly in Macbeth's relationships with Lady Macbeth and with the weird sisters. Differences between Macbeth and Macduff's responses to the oedipal dilemma are also defined. An understanding of these themes provides the context for understanding the underlying hostility toward women implicit throughout the play. PMID- 3101096 TI - Autodestruction and nonexistence: two distinct aspects of the death drive. AB - The concept of the death drive is more frequently employed by European than by American psychoanalysts, although it is not unanimously accepted even by the former. In recent years there have been attempts to disconnect the longstanding theoretical link between the drive and aggression, in keeping with the observations of various nondestructive components of the death drive. A hitherto unmentioned aspect of this drive is the yearning for nonexistence, a shadow-like counterpoise to life, expressed by two analysands. Both had childhood histories of life-threatening disease without sufficient compensatory maternal presence at the time. Both displayed massive dissociation from their own body and its vital functions, as well as from objects and their representations. The death drive could be viewed as a continuum with the autodestructive aspect, or the striving for death, at one end, and the component of nonbeing, or the yearning for nonexistence, at the other end. PMID- 3101097 TI - A personal myth--Yukio Mishima: the Samurai Narcissus. PMID- 3101098 TI - Antagonism of the behavioral effects of cocaine and d-amphetamine by prazosin. AB - Key pecking by pigeons was maintained under a 30-response fixed-ratio schedule of food delivery; lever pressing by squirrel monkeys was maintained under a 3-min fixed-interval schedule of food delivery. Administered alone, d-amphetamine (0.1 3.0 mg/kg), cocaine (1.0-3.0 mg/kg) and bupropion (1.0-30 mg/kg) either did not affect or decreased fixed-ratio responding of pigeons, whereas d-amphetamine (0.056-0.3 mg/kg) either increased or decreased (0.56 mg/kg) responding of monkeys maintained under the fixed-interval schedule. Prazosin, a selective centrally-active alpha 1 antagonist, produced a dose-dependent reversal of the rate-decreasing effects of d-amphetamine and cocaine but not of bupropion on fixed-ratio responding in pigeons. Prazosin also reversed both the rate increasing and rate-decreasing effects of d-amphetamine on fixed-interval responding of squirrel monkeys. In contrast, the non-selective alpha-antagonist phentolamine enhanced d-amphetamine-induced decreases in fixed-ratio responding. These findings suggest that the behavioral effects of d-amphetamine and cocaine are produced at least in part by activation of central alpha 1 receptors. Prazosin may be a useful tool for better understanding the mechanisms through which cocaine, amphetamine, and other abused stimulant drugs exert their potent behavioral effects. PMID- 3101099 TI - Negative reinforcing properties of naloxone in the non-dependent rhesus monkey: influence on reinforcing properties of codeine, tilidine, buprenorphine, and pentazocine. AB - Scheduled infusions of naloxone (1-100 micrograms/kg/inf.) and of buprenorphine (250 micrograms/kg/inf.) generated drug avoidance behavior in the non-dependent rhesus monkey under a continuous avoidance-escape paradigm. Pentazocine (1-100 micrograms/kg/inf.) codeine, (1-100 micrograms/kg/inf. and tilidine (1-250 micrograms/kg/inf.) were ineffective. Addition of varying doses of naloxone to scheduled infusions of codeine, tilidine, and pentazocine generated avoidance behavior not present with scheduled infusions of these opioids alone. The naloxone doses necessary for generation of avoidance behavior were low with the agonists codeine and tilidine, higher with the weak antagonist pentazocine, and highest with the strong antagonist buprenorphine. When monkeys were presented with the fixed tilidine-naloxone combination (100 + 8 parts) and pentazocine naloxone combination (100 + 1 part) and the buprenorphine-naloxone combination (100 + 66 parts) presently in clinical use only the tilidine-naloxone combination generated drug avoidance behavior to an appreciable extent. PMID- 3101100 TI - Aggression during morphine withdrawal: effects of method of withdrawal, fighting experience, and social role. AB - Offensive and defensive components of aggressive behavior were determined in resident and intruder mice. Withdrawal aggression was measured after the removal of a subcutaneous morphine pellet or after precipitation by naloxone in naive mice and after removal of a morphine pellet in mice with prior fighting experience. In naive mice, removal of a morphine pellet led to increases in attack bites and threats but naloxone-precipitated withdrawal led to decreases in these behaviors and to increases in defensive posturing, escape attempts and vocalizations. Prior fighting experience abolished the enhanced attack behaviors of resident mice following morphine pellet removal, but led to heightened defensive behavior in intruder mice. The behavior of intruder mice appeared more sensitive to naloxone administration than the behavior of resident mice; naloxone influenced not only intruder defensive behavior, but also other non-aggressive behaviors. The social role of the drug recipient and his prior history of aggressive behavior are important determinants of morphine and naloxone effects on aggression. PMID- 3101101 TI - Benactyzine increases alarm call rates in the squirrel monkey. AB - The effects of benactyzine (0.01-3.0 mg/kg) were examined on the frequency of alarm calls of squirrel monkeys in a laboratory setting. Under baseline conditions, few calls occurred, and neither saline nor a low dose (0.01 mg/kg) of benactyzine increased calling. Higher doses (0.03-3.0 mg/kg) of benactyzine significantly increased call rate (to 1-2 calls per s) in a dose-dependent manner. The rate-increasing effect of benactyzine on alarm calls appears to be related to a central antimuscarinic effect, as it could be partially blocked by 0.01 mg/kg physostigmine, completely blocked by 0.1 mg/kg physostigmine, but was not blocked at all by 0.1 mg/kg neostigmine. Neither of these cholinomimetics increased call rates when given alone. These findings show that benactyzine can increase alarm call rates in squirrel monkeys under defined laboratory conditions, and may serve as a useful pharmacological probe to study neurochemical mechanisms mediating the production of this type of vocalization. In the squirrel monkey, one such mechanism apparently involves a cholinergic substrate. PMID- 3101102 TI - Effects of smoking on haloperidol and reduced haloperidol plasma concentrations and haloperidol clearance. AB - Plasma concentrations of haloperidol and its reduced metabolite (reduced haloperidol) were investigated in cigarette smokers (N = 23) and nonsmokers (N = 27). Steady-state plasma concentrations were obtained 12 h post bedtime dose. Haloperidol and reduced haloperidol concentrations were determined by RIA. Reduced haloperidol was separated by selective succinylation and liquid chromatography. Patients were clinically assessed with the Clinical Global Impression Scale (CGIS). Smokers had significantly lower haloperidol and reduced haloperidol plasma concentrations than nonsmokers (P less than 0.01, P less than 0.05). Clearance of haloperidol was significantly greater in smokers compared to nonsmokers (P = 0.0052). CGIS assessments did not show significant differences between smokers and nonsmokers. Plasma concentrations should be carefully monitored when patients either start or stop smoking. PMID- 3101103 TI - Lack of circadian rhythm in plasma levels of 3,4-dihydroxyphenylethyleneglycol in healthy human subjects. AB - In order to investigate the possible existence of a circadian rhythm in plasma free and sulfate-conjugated 3,4-dihydroxyphenylethyleneglycol (DOPEG), the plasma levels of this metabolite (and for comparison, of melatonin and cortisol) were measured in seven healthy volunteers at 4-h intervals over a period of 24 h. Plasma concentrations of melatonin and cortisol showed distinct diurnal variations with acrophases at 2.5 h and 8.5 h, respectively. In contrast, plasma free DOPEG levels were relatively stable over the 24-h period studied. Sulfate conjugated and free + sulfate-conjugated DOPEG levels showed a slight, non significant increase in the early afternoon. These results indicate that in contrast to plasma 3-methoxy 4-hydroxyphenylethyleneglycol, plasma free and conjugated DOPEG levels do not exhibit a circadian rhythm. PMID- 3101104 TI - Response repetition in pigeons: pharmacological and behavioral specificity. AB - Using a reinforcement schedule that arranges random sequences of reinforcements over two response keys, low and high probabilities of repetition of non reinforced responses were generated in two groups of pigeons (n = 3 per group) by varying the probability of reinforcement for responding on the key to which reinforcement was assigned. Unlike rats, the pigeons did not show a tendency to repeat just-reinforced responses, but showed a strong position bias, that was reduced by additional feeding and extinction, but not by any of the drug treatments. Apomorphine increased response repetition, irrespective of the control probability of repetition; d-amphetamine increased low probabilities of repetition, but decreased high probabilities. Chlordiazepoxide and scopolamine selectively decreased high probabilities of repetition; phencyclidine and pentobarbital selectively increased low probabilities of repetition. Morphine, haloperidol, chlorpromazine, additional feeding, and extinction did not affect repetition of non-reinforced responses. Extinction increased perseveration, whereas drug effects on perseveration were not observed. Drug-induced changes of patterning of responses as exemplified herein by drug-induced alterations of repetitiveness may be relevant to the interpretation of drug effects upon performance brought about by other behavioral processes such as discrimination. PMID- 3101105 TI - Effects of vasopressin, des-glycinamide vasopressin and amphetamine on a combined passive and active avoidance task. AB - The effects of peripherally injected arginine vasopressin (AVP), its des glycinamide derivative (DGAVP), which has limited pressor activity, and d amphetamine (AMP) were studied on a combined passive and active avoidance task (Carew 1970). In this procedure, the rat experiences mild foot-shock in one of two distinctively coloured compartments, followed by drug treatment. On the next day, re-entry latency into either of the two compartments is measured (latency index), and the actual compartment chosen is noted (choice index). Both measures were affected by the intensity of the shock. A moderate dose of AVP (25 micrograms/kg) increased latencies, but only when a relatively low shock intensity was used; choice was not markedly affected. DGAVP did not significantly affect performance under any condition. AMP affected latency scores as well as choice behaviour at the lower shock level but, presumably due to "ceiling" effects, did not exert an effect in the high shock condition. The negative DGAVP findings suggest that the behavioural potency of peripherally injected AVP was due to pressor activity, rather than any direct action on cognitive mechanisms. Moreover, this indirect AVP effect on mnemonic performance was relatively weak, since only the latency, but not choice, measure was significantly affected. It is concluded that the Carew paradigm provides a more comprehensive assessment of behaviour than traditional passive or active avoidance procedures. PMID- 3101106 TI - Analysis of the role of drug-predictive environmental stimuli in tolerance to the hypothermic effects of the benzodiazepine midazolam. AB - The role of classical conditioning processes in the development of tolerance to the hypothermic effects of the short-acting benzodiazepine midazolam was studied in three experiments in rats. The experiments were all designed so that one set of environmental stimuli reliably predicted drug treatments whilst another set of stimuli predicted control (vehicle) treatment. According to the classical conditioning account of tolerance, the degree of tolerance observed should be greater in the presence of drug-predictive stimuli than in their absence, i.e. tolerance should show environmental (context) specificity. A preliminary study was conducted to determine the dose- and time-effect curves for midazolam-induced hypothermia. The results of this study provided essential background data for the design of all the subsequent tolerance studies. In the first tolerance study, it was found that virtually complete tolerance developed to the hypothermic effects of 4 mg/kg (IP) midazolam given on alternate days. However, the observed tolerance was clearly not environmentally specific. Since there is evidence that conditioned tolerance to some drug effects develops most readily if drugs are given at low doses with long inter-injection intervals, a second study was conducted with a lower (1.6 mg/kg IP) dose of midazolam, which was given every 5th day. Despite these procedural changes, the second study indicated that the observed tolerance again did not show context specificity, even though tolerance developed rapidly with the lower dose of a short acting drug which was given infrequently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101107 TI - The effects of smoking on electrocortical arousal in coronary prone (type A) and non-coronary prone (type B) subjects. AB - Twenty-nine Type A subjects, (greater than 75 percentile on the Jenkins Activity Survey) and 28 Type Bs (less than 25 percentile of the survey) were asked to smoke one cigarette (1.0 mg nicotine, 16 mg tar, 14 mg CO) using a standardized smoking procedure. Significant differences between baseline and smoking conditions were noted in the distribution of electrocortical activity for both groups. In addition, a shift from EEG low frequency high amplitude (alpha) events to high frequency low amplitude activity (beta) was noted for the As, while the Bs showed enhanced very low frequency high amplitude (theta) activity. A striking parallel was observed between the behavioral predisposition of the subject (A/B) and the possible function of the underlying neurological structure mediating the observed EEG changes. It is suggested that the electrocortical changes observed for the As during smoking are mediated by reticular (ARS I) arousal. Enhanced reticular activity may coincide with an increased rate of information processing, attention and vigilance. On the other hand, the electrocortical changes observed for the Type Bs may represent enhanced activity of the limbic system (ARS II) with could coincide with stimulation of the reward/pleasure centers. Smoking may produce a pattern of neurophysiological arousal which parallels the behavioral tempo of the individual. Possible differences in in vivo regulation of nicotine cholinergic binding sites are also discussed. PMID- 3101108 TI - Cigarette withdrawal symptoms in adolescent smokers. AB - One hundred and sixteen female adolescent smokers were asked about withdrawal symptoms experienced during past attempts to give up smoking for good. Sixty three percent reported difficulties during abstinence of the kind experienced by adult smokers. Daily smokers were more likely to report withdrawal effects than non-daily smokers (74% versus 47%, P less than 0.005). Reported experience of withdrawal symptoms was positively related to self-reports of cigarette consumption and depth of inhalation and nicotine intake as indexed by salivary cotinine concentrations. Reported occurrence of at least one withdrawal effect correlated positively with nicotine intake after controlling for behavioural variables. Our results indicate that teenage smokers are likely to suffer withdrawal symptoms when they try to give up. Behavioural factors and expectations based on observations of adults may have played a part in their experience of withdrawal, but it is also likely that pharmacological factors are implicated even at this early stage. PMID- 3101110 TI - The effect of training dose on discrimination of compound drug-exteroceptive stimuli. AB - Rats were trained to discriminate between two compound stimulus arrays that included exteroceptive (ES) and interoceptive (IS) stimulus components. The ES components were illumination and tactile cues, and the IS components were produced by d-amphetamine (A) or Na pentobarbital (P) treatment (drug versus drug discrimination). The relative ES-IS strength was then determined by testing with "mismatched" stimulus arrays consisting of combinations of ES and IS components that had not been presented simultaneously during training. Additional tests were done with ES only (no drug treatments). At training doses of 0.8 mg/kg A versus 10 mg/kg P, the ES were less salient than, but did share stimulus control with, the stronger IS components. In a second group, trained with lower doses (0.5 mg/kg A versus 4 mg/kg P), the ES were much more salient than the IS, although again, both types of stimuli did acquire some control. This dose-related sharing of stimulus control between ES and IS components is similar to relationships among components of compound arrays consisting entirely of ES, and thus further illustrates similarity between drug-produced and exteroceptive stimuli. PMID- 3101112 TI - Surgeon General's report on acquired immune deficiency syndrome. PMID- 3101111 TI - Retrograde memory enhancement by diazepam: its relation to anterograde amnesia, and some clinical implications. AB - The effect of diazepam on retention of an inhibitory avoidance task was investigated in mice. In Experiment 1, animals were trained in this task, and tested for retention 24 h later. The mice received, 20 min after training, an IP injection of either diazepam (2 mg/kg) or saline; half of the mice in each treatment group were exposed, 40 min after avoidance training (and 20 min after the injections) to a Y maze. Exposure to the Y maze disrupted retention of the avoidance task in the saline-treated animals, and enhanced it in the diazepam treated mice. Retention of habituation to the Y maze was impaired in the diazepam group. The effect can be explained by an interaction of the drug with the Y maze, by which exposure to the Y maze became facilitatory, instead of deleterious, to retention of the avoidance task. This may or may not be related to anterograde amnesia for the Y maze; and may be related to effects of diazepam seen in clinical practice. In Experiment 2, diazepam was given prior to, instead of after, inhibitory avoidance training; it caused anterograde amnesia for this task, which was not reversed by pre-test diazepam, and was therefore not due to state dependency. In conclusion, the effect of diazepam on inhibitory avoidance learning depends on the time at which the drug is given. A pretraining injection causes amnesia, whereas a post-training injection, while ineffective per se, may facilitate retention of the task when it is followed by exposure to a habituation procedure. PMID- 3101109 TI - Sex differences in muscarinic receptor binding after chronic ethanol administration in the rat. AB - Male and female rats were administered ethanol (5% v/v) in a liquid diet for 18 weeks. Pair-fed control animals were fed the same diet except that dextrose was substituted isocalorically for ethanol. Normal controls received a commercial laboratory chow for the same duration. Results showed that, in females, chronic ingestion of an ethanol liquid diet significantly increased the number of muscarinic receptor binding sites compared to both control groups. In contrast, for males, there was no significant difference in the mean number of binding sites among the treatment groups. Furthermore, the mean maximum number of binding sites for males and females varied across brain areas. Males had a significantly greater number of receptor binding sites than females in the striatum, while females had a greater number in the cortex. It was suggested that the geuder differences observed in the present study could be mediated by hormonal effects on central muscarinic functioning. PMID- 3101113 TI - More on the choking controversy. PMID- 3101114 TI - Response to Dr. Waldron's critique of smoking studies. PMID- 3101115 TI - Use of all age data may change results of Hansen's disease study. PMID- 3101116 TI - The prevention and control of chronic diseases: reducing unnecessary deaths and disability--a conference report. AB - Effective, yet underused, preventive measures exist to ameliorate such important public health problems as hypertension, coronary artery disease, and cervical cancer. The First National Conference on Chronic Disease Prevention and Control was convened in September 1986 by the Association of State and Territorial Health Officials and the Centers for Disease Control, Public Health Service, to disseminate information on successful chronic disease programs currently being implemented and to identify barriers to more wide-spread application of state-of the-art prevention technology. This report briefly summarizes the deliberations of conference working groups (composed primarily of State and Federal public health officials) that addressed these issues. Numerous suggestions for improved surveillance, applied research, and training related to chronic disease prevention and control were offered, as well as ideas on organizing and marketing chronic disease intervention programs. The conference clearly identified a pressing need for a coalition of public health agencies and interested professional and voluntary organizations, as well as a coherent national agenda to combat chronic diseases. PMID- 3101117 TI - Physicians' and patients' views of problems of compliance with diabetes regimens. AB - Thirty noninsulin-dependent diabetic patients and 30 residents in internal medicine at Cleveland Metropolitan General Hospital were surveyed regarding their perceptions of the difficulties of complying with diabetic regimens. Three main components of compliance were investigated (medication, diet, and urine testing), and each component was broken down into three separate tasks. Physicians and patients rated the components on a scale of 0 to 10. For each of the three components, physicians rated compliance tasks as more difficult than did the patients. In addition, statistically significant differences were found in the difficulty ratings given separate tasks within each component of compliance. Finally, a statistically significant interaction reflected differences in difficulty ratings of patients compared with those of physicians for the various tasks associated with dietary compliance. Results indicated that physicians and diabetic patients differ in their perceptions of compliance difficulties. It would appear that either physicians were overestimating the difficulty that diabetic patients experience with various tasks or that patients underestimated (or underreported) their difficulty. Possible sources of these differences and their implications for patient and physician education are discussed. PMID- 3101119 TI - National Center for Nursing Research is ready for action at NIH. PMID- 3101118 TI - Use of hospital-based ambulatory care in New York City's Health Manpower Shortage Areas. AB - The development of a comprehensive data base for hospital-based ambulatory care has made possible the accurate determination of each community's use of hospitals in New York City and permits a reliable estimation of all ambulatory care received by residents of Health Manpower Shortage Areas (HMSAs). In spite of the city's abundant supply of private practitioners and widespread Medicaid coverage, residents of HMSAs in New York City are heavily dependent on hospital-based ambulatory care. Contrary to commonly held notions, however, HMSA residents do not appear to overuse hospital-based ambulatory care. Rather, that use appears to be quite modest, given their poorer health status. PMID- 3101120 TI - Periodontal effects and dental caries associated with smokeless tobacco use. AB - The prevalence of smokeless tobacco use has been increasing in the United States with concomitant social, medical, legal, and regulatory ramifications. This paper examines the association between the use of smokeless tobacco and the occurrence of periodontal disease and dental caries. Existing literature consists primarily of case reports and cross-sectional studies among teenagers. The limited evidence suggests an association between smokeless tobacco use and gingival recession. There is insufficient evidence to support any associations between smokeless tobacco use and gingivitis, periodontitis, or dental caries. Methods to improve future epidemiologic research to examine possible associations between smokeless tobacco use and periodontal effects or dental caries are discussed. PMID- 3101121 TI - Occupational health and safety risks and potential health consequences perceived by U.S. workers, 1985. AB - Data from the Health Promotion and Disease Prevention Questionnaire, part of the 1985 National Health Interview Survey, were used to report workers' perceptions of occupational risk in their present jobs. This information will be used to monitor progress between 1985 and 1990 toward achieving broad goals in health promotion and disease prevention. The proportions of currently employed persons who perceived exposure to health-endangering substances, work conditions, or risks of injuries were reported for age, race, sex, and occupation groups. Occupational groups were further characterized by the proportion of men and women who reported specific exposures (such as exposure to chemicals or to loud noise) and specific health consequences of exposure (such as risk of developing cancer or hearing impairment). Greater proportions of men than women reported perceived risk from exposure to health-endangering substances, work conditions, and injuries in their present job. Also, a greater proportion of workers perceived risk of injury in their present job than other occupational risk categories. The greatest proportions of perceived exposure to occupational risk were reported by farm operators and managers, police and firefighters, and by workers in forestry and fishing occupations. Among workers reporting perceived exposures, chemicals, noise, and risk of injuries from vehicles were cited by the greatest proportion of workers, as were such health consequences as lung and respiratory problems and hearing impairment. Data from this study may be used to target employment groups for health promotion or education and to develop indepth studies of specific occupational groups to reduce or prevent risk at the worksite. PMID- 3101122 TI - Self-reported stress: findings from the 1985 National Health Interview Survey. AB - The National Health Interview Survey's 1985 Health Promotion and Disease Prevention Questionnaire included questions on the amount of stress experienced in the past 2 weeks, the effect of stress on health, thoughts about seeking help for personal or emotional problems, and actual help-seeking behaviors. This report examines responses to these questions and analyzes self-reported levels of stress by sex and other respondent characteristics. In 1985, an estimated 34 million people aged 18 years and older experienced "a lot" of stress in the 2 week period preceding the interview. Women were more likely than men to report a lot of stress (23 percent versus 18 percent), and respondents 65 years of age or older were more likely than younger respondents to report "almost no" stress. An estimated 21 million people (13 percent) believed that, over the past year, stress had "a lot" of effect on their health. Seventeen percent of the population considered seeking help in the past year for personal or emotional problems from family, friends, helping professionals, or self-help groups. Sixty-nine percent of those who thought about seeking help reported that they actually did seek help. In terms of health practices, men and women who reported higher levels of stress than others of their sex also were more likely to report that they rarely or never ate breakfast, slept 6 or fewer hours per night, were physically less active than their peers, or drank more alcoholic beverages than usual in the 2 weeks prior to the survey. PMID- 3101123 TI - Estimates of the direct and indirect costs of acquired immunodeficiency syndrome in the United States, 1985, 1986, and 1991. AB - This study presents three estimates--ranging from low to high--of the direct and indirect costs of the AIDS epidemic in the United States in 1985, 1986, and 1991, based on prevalence estimates provided by the Centers for Disease Control (CDC). According to what the authors consider their best estimates, personal medical care costs of AIDS in current dollars will rise from $630 million in 1985 to $1.1 billion in 1986 to $8.5 billion in 1991. Nonpersonal costs (for research, screening, education, and general support services) are estimated to rise from $319 million in 1985 to $542 million in 1986 to $2.3 billion in 1991. Indirect costs attributable to loss of productivity resulting from morbidity and premature mortality are estimated to rise from $3.9 billion in 1985 to $7.0 billion in 1986 to $55.6 billion in 1991. While estimated personal medical care costs of AIDS represent only 0.2 percent in 1985 and 0.3 percent in 1986 of estimated total personal health care expenditures for the U.S. population, they represent 1.4 percent of estimated personal health care expenditures in 1991. Similarly, while estimated indirect costs of AIDS represent 1.2 percent in 1985 and 2.1 percent in 1986 of the estimated indirect costs of all illness, they are estimated to rise to almost 12 percent in 1991. Estimates of personal medical care costs were based on data from various sources around the United States concerning average number of hospitalizations per year, average length of hospital stay, average charge per hospital day, and average outpatient charges of persons with AIDS. For estimating the indirect costs the human capital method was used, and it was assumed that average wages and labor force participation rates of persons with AIDS were the same as those for the general population by age and sex. PMID- 3101124 TI - 1985 NHIS findings on public knowledge and attitudes about oral diseases and preventive measures. AB - Two objectives for the nation for 1990 set goals related to the need for schoolchildren and adults to understand the causes of oral diseases and methods of prevention. Five questions related to these objectives were included in the 1985 National Health Interview Survey. Survey responses of adults ages 18 years and older indicated that while the public is generally aware of the importance of a number of factors in the prevention of tooth decay, only 18 percent had both heard of, and knew the purpose of, dental sealants. At the same time, the public fails to discriminate between effective disease preventive factors related to periodontal diseases as opposed to those related to dental decay. Knowledge of oral disease prevention modalities generally varies across educational, income, age, and racial categories. However, there appears to be little variation in knowledge by gender. Additional information from upcoming surveys may shed more light on the relationships between knowledge of oral diseases and their prevention and personal preventive practices. PMID- 3101125 TI - 1985 NHIS findings: nutrition knowledge and baseline data for the weight-loss objectives. AB - A nutrition objective for the nation is that, by 1990, 50 percent of the overweight population should have adopted weight regimens, balancing diet and physical activity. More than half of the overweight respondents in the 1985 National Health Interview Survey were trying to lose weight, and almost half of this group reported both increasing their physical activity and decreasing their intake of calories. Dietary restriction without exercise was the next most common weight-loss regimen, suggesting that educational efforts should emphasize the need to increase physical activity as part of appropriate weight-loss regimens. Attempts to lose weight were reported frequently among those of normal and lean weight as well as among those who were overweight, especially among women and the better educated. About one-fifth of already lean young women reported attempting weight loss, an indication that some inappropriate dieting is probably occurring, suggesting the need for caution in public health promotion of weight loss. Another 1990 objective is that 90 percent of adults should understand that eating fewer calories or increasing activity, or both, is essential to lose weight. More than 70 percent of adults in this survey were able to identify these as the two best ways to reduce weight, with greater proportions of the younger adults and the more highly educated being knowledgeable. The survey also provided data for an objective that targets some nutrition education and counseling as part of all routine health contacts with health professionals by 1990. Twenty-nine percent of all women and 22 percent of all men reported that eating proper foods was discussed sometimes or often in routine contacts. PMID- 3101126 TI - Toward the 1990 objectives for smoking: measuring the progress with 1985 NHIS data. AB - The Health Promotion and Disease Prevention component of the 1985 National Health Interview Survey allowed us to measure the progress made toward achieving the 1990 objectives for the nation concerning cigarette smoking. The first smoking related objective, namely, to reduce to below 25 percent the proportion of the U.S. population who smoke, has not been achieved. Today 31 percent of the population smoke. More than 85 percent are aware of the special risk of developing and worsening chronic obstructive lung disease, chronic bronchitis, and emphysema among smokers. More than 90 percent are aware that smoking is a major cause of lung cancer; however, awareness of the risk of laryngeal, esophageal, bladder, and other kinds of cancer from smoking is not so great. More than 85 percent are aware that cigarette smoking is one of the major risk factors for heart disease. In general, then, the 1990 objectives concerning the population's knowledge of the health consequences of cigarette smoking have been met. PMID- 3101127 TI - Perceptions of risks of smoking and heavy drinking during pregnancy: 1985 NHIS findings. AB - As part of the Health Promotion and Disease Prevention Questionnaire administered in the 1985 National Health Interview Survey, nearly 20,000 respondents ages 18 44 answered questions about their awareness of the risks of smoking and heavy drinking during pregnancy. In reference to smoking, interviewers asked about miscarriage, stillbirth, prematurity, and low birth weight; in reference to heavy drinking, they asked about miscarriage, mental retardation, low birth weight, and birth defects, as well as fetal alcohol syndrome. For each of these adverse outcomes, a majority of subjects acknowledged increased risk because of smoking or heavy drinking during pregnancy. The range was 66-80 percent of respondents for the four questions on smoking, with the perceived association to smoking strongest for low birth weight. Approximately 84 percent of respondents associated heavy drinking with increased risk for each of the suggested pregnancy outcomes. Smoking seemed to be perceived to pose a lesser risk to pregnancy than heavy drinking. This relative lack of awareness of the pregnancy risks of smoking was more apparent among respondents with less education and more pronounced among blacks than whites. Women were more likely than men to express some opinion on these pregnancy-related questions and were more cognizant than men of the risks. On this limited survey, Americans ages 18-44 were not very knowledgeable about fetal alcohol syndrome. Among the 55 percent who had heard of fetal alcohol syndrome, fewer than one in four correctly identified it as a set of birth defects when offered three possible definitions. It will be interesting to correlate responses to these "knowledge" questions with NHIS data still forthcoming on reported actual smoking and drinking behavior among women respondents who were recently pregnant. PMID- 3101129 TI - Minimizing drug misuse among elders: a proposal. AB - This proposal is aimed at reducing the risk of adverse drug interactions that may occur when over-the-counter (OTC) preparations are taken in conjunction with prescription drugs in an unsupervised regimen. Such polymedicating is practiced widely among the elderly. A pilot program would be implemented over 12 months at three drugstores of a major retail chain. A barcode-based computer system would be used to identify potential adverse drug interactions for elderly customers. All volunteers admitted to the study, controls and subjects, would agree to buy all their medications, prescriptions and OTC, at the participating pharmacies. In return, the volunteers would receive discounts of 25 percent on prescription and OTC drugs and 10 percent on vitamins. Study subjects (N = 375) would carry barcoded identification (BID) cards that would activate the computerized program to assess each purchase for compatibility with their other medications; controls (N = 375) would carry "dummy" BID cards that would prompt the computer to approve all drug purchases. A final comparison of the subjects with the controls, as well as with a sample of elderly residents selected randomly from the community, would determine whether such a computerized, commercially based drug use review system could reduce the potential for adverse interactions between OTC and prescription drugs among the elderly. PMID- 3101128 TI - A plan to prevent adolescent pregnancy and reduce infant mortality. AB - In Illinois, particularly in Chicago, the infant mortality rate is higher than that for the nation as a whole. Unless infant mortality in Illinois declines at a faster rate, the State will not meet the objective for reducing infant mortality specified by the Surgeon General of the Public Health Service. Low birth weight infants are at high risk of medical problems, if not death, and teenage mothers have an increased risk of bearing low birth weight infants. This paper presents a program aimed at the primary prevention of adolescent pregnancy. The three component, interactive program--sex education, adolescent clinic services, and community support and involvement--is proposed for preventing adolescent pregnancy which, in turn, will decrease the rate of births of low birth weight infants and, consequently, the rate of infant mortality in target areas of Illinois. Medical and college students will be trained to teach the sex education course and to serve as counselors. A clinic will provide primary care, contraceptive education, and access to contraceptives. The clinic staff will be a resource for the community as well as for the adolescents. In the target areas, church and community members will sponsor health fairs and discussions of adolescent pregnancy at church and at parent-teacher association meetings. The overlapping activities of the instructors, clinic personnel, and church and community members will give continuity and consistency to the prevention message directed to the adolescents. PMID- 3101130 TI - Smokeless Tobacco Reduction Program. AB - To reduce the incidence and prevalence of oral cancer, the Smokeless Tobacco Reduction Program will consist of a mass media campaign, public oral screening, and a week-long school health program for 350 students in the seventh, eighth, and ninth grades in Willows, Glenn County, CA. Mass media will include radio, television, newspapers, posters, and literature. The program will use resources of the public health department and junior high school; it will also depend on 8 teachers and 25 peer leaders, all trained in the program. Reducing the use of smokeless tobacco is the program's objective. If that goal is achieved, the program will reduce oral cancers in the target population by 75 percent within 10 years. The incidence of leukoplakia will be reduced by 50 percent within 3 years of the end of the program. By the end of the program, 90 percent of the target population will be able to identify warning signs of oral cancer and leukoplakia, and 85 percent of the students will no longer believe that use of smokeless tobacco is less harmful than smoking. As a result of the program, use of smokeless tobacco will not be viewed favorably by 80 percent of the target population; usage will be regarded as socially unacceptable. PMID- 3101131 TI - Filter elution analysis of the effect of alpha-difluoromethylornithine on X-ray induced DNA damage in 9L cells. AB - We used the filter elution technique to study DNA single- and double-strand scission under denaturing alkaline and nondenaturing conditions in X-irradiated 9L rat brain tumor cells. The amount of DNA damage determined by the alkaline elution assay was similar for different lysis conditions (sodium dodecyl sulfate and sarkosyl) and DNA fluorometric assays (Hoechst 33258 and 3,5-diaminobenzoic acid dyes). Therefore, results of the filter elution assay obtained with the various methods can be compared directly. Using these assays, we found that there was no significant change in the susceptibility to X-ray-induced DNA damage, measured either as single- or double-strand breaks, in 9L cells depleted of polyamines by treatment with alpha-difluoromethylornithine. Results obtained by filter elution are different from results obtained with viscoelastometry, which suggests that the two methods may resolve the effects of changes in DNA structure in different ways. PMID- 3101133 TI - Low level X-radiation effects on carcinogenesis by 7,12-dimethylbenz(a)anthracene in Syrian hamster cheek pouch epithelium: acute vs fractionated radiation dose studies. AB - Studies examined the effects of acute and fractionated low to moderate level X ray exposures on hamster cheek pouch carcinogenesis in vivo by 7,12 dimethylbenz(a)anthracene (DMBA). Animals were grouped by treatment as follows: acute doses of 0.85-3.40 Gy X rays; 17 once weekly doses of 0.01-0.20 Gy X rays (fractionated radiation); topical DMBA for 10 weeks; DMBA plus fractionated radiation starting together; DMBA plus acute radiation in Week 1 or 10 of DMBA treatments; and sham irradiation, DMBA vehicle, or anesthesia controls. After 44 weeks, hamsters were sacrificed, and their cheek pouches were excised, serially sectioned, and examined by light microscopy for histopathology. No histologic changes were observed in radiation-only hamsters. Carcinoma incidences in DMBA only groups ranged from 45 to 60%. Carcinoma incidences were greater in groups receiving DMBA plus fractionated radiation than in groups receiving either acute radiation + DMBA or DMBA alone. Carcinoma incidences in acute radiation plus DMBA groups were lower than those in DMBA-only groups. These results suggest complex interactions between radiation and DMBA, perhaps with radiogenic cell killing being a principal factor in acute radiation + DMBA groups, and reciprocal additive or synergistic effects of radiation and DMBA on cancer induction and manifestation in fractionated radiation + DMBA groups. PMID- 3101134 TI - Preirradiation of medium induces a subsequent stimulation or inhibition of growth according to the physiological state in Synechococcus lividus in culture. AB - The proliferation of Synechococcus lividus cells grown in preirradiated medium was compared with the proliferation of cells grown in a shielded or freshly prepared medium. Aging of medium in a shielded chamber resulted in a slight inhibiting effect on growth in every phase of the cell cycle which was used. Preirradiation of medium resulted in a stimulation of growth observed on Day 7 in cultures inoculated with cells selected in the deceleration phase and an inhibition of growth in cultures inoculated with exponentially growing cells. Addition of catalase (100 U X ml-1) counteracted the stimulating effect but did not modify the inhibiting effect induced by preirradiated medium. Results demonstrated the indirect effect of low doses of irradiation, implying the presence of hydrogen peroxide in radiostimulation and other radioproducts in the inhibitory effect. PMID- 3101132 TI - The effect of oxygen on the radiolysis of tyrosine in aqueous solutions. AB - The effect of oxygen on the radiolysis of tyrosine in aqueous solutions was investigated by using gamma and pulsed electron irradiation. Steady-state radiolysis was reexamined and extended to include the effect of pH and determination of hydrogen peroxide. The loss of tyrosine, G(-Tyr), during irradiation and yields of 3,4-dihydroxyphenylalanine, G(DOPA), and hydrogen peroxide, G(H2O2), are determined in the pH range from 1 to 9. In the whole pH range used G(-Tyr) equals G(DOPA), and a higher G(H2O2) than expected was observed. In slightly acid and neutral media, both G(-Tyr) and G(DOPA) equal the yield of hydroxyl radicals, GOH, formed in the radiolysis of water, while the excess of hydrogen peroxide equals 1/2 GOH. Hence it was concluded that all tyrosine OH-adducts react with oxygen yielding peroxy radicals. In acid and alkaline media all measured yields decrease. This is caused by formation of tyrosine phenoxyl radicals (TyrO), which react with superoxide anion (O2-) and hydroperoxy (HO2) radicals regenerating tyrosine. By using pulse radiolysis K(TyrO + O2) less than or equal to 2 X 10(5) mol-1 dm3 s-1 and k(TyrO + O2-) = (1.7 +/- 0.2) X 10(9) mol-1 dm3 s-1 were determined. On the basis of the results, a reaction mechanism is proposed. PMID- 3101135 TI - [Cerebral seizure following lumbar myelography with iopamidol]. AB - This is a report of a case of a serious side effect following lumbar radiculography with the water soluble contrast medium Iopamidol. The complication consisted of a generalized seizure after an episode of myoclonic jerking of the legs. This was the first complication in a series of 1070 lumbar and cervical myelograms with this medium. PMID- 3101137 TI - Sequential changes of skin conductance activity in rats after intraventricular administration of 6-hydroxydopamine. AB - Thirty two male Wistar strain rats were trained to have their skin conductance activity recorded through the soles of their hind limbs, and sequential changes of this activity after the intraventricular administration of 6-OHDA (200 micrograms) were studied. The intact rats showed SCR and its habituation to repeated auditory stimuli (500 Hz, 90 dB, 1 sec). The 6-OHDA treatment obliterated SCR and reduced the rate of spontaneous fluctuation in the early stage after the treatment. From the second day to one week after the treatment, with recovery of the spontaneous fluctuation rate, the SCR tended to reappear, and its habituation gradually slowed down. Two and three weeks after the treatment, the 6-OHDA rats usually showed habituation failure of SCR, but default of SCR was still observed at times. These findings suggest that denervation of the catecholaminergic fibers by intraventricular 6-OHDA is responsible for the obliteration of SCR, and denervation supersensitivity, which develops later, may be the cause of its habituation failure. The mechanisms underlying abnormal skin conductance activity of schizophrenia were discussed in line with the catecholamine hypothesis of this disease. PMID- 3101136 TI - Spinal and paraspinal neurofibromatosis: surface coil MR imaging at 1.5 T1. AB - Twelve patients with neurofibromatosis affecting the spine and paraspinal regions were examined with magnetic resonance (MR) imaging performed using a 1.5-T magnet, surface coils, and spin-echo pulse sequences. In all 11 patients with neurofibromas, these tumors had slightly greater signal intensity than muscle on T1-weighted images and markedly increased signal intensity on T2-weighted images. In seven patients central areas of decreased signal intensity within the neurofibromas were demonstrated on T2-weighted images. In one patient these central areas corresponded pathologically to relatively fibrous components of the tumors surrounded by myxoid matrix. Five patients had extensive plexiform neurofibromatosis, one had lateral meningoceles, one had a neurofibrosarcoma, three had extradural spinal cord compression, and two had cystic intramedullary tumors of the spinal cord. The ability to obtain high-resolution, multiplanar images in a noninvasive fashion makes surface coil MR imaging an ideal technique for evaluating neurofibromatosis involving the spinal cord, spinal canal, and paraspinal soft tissues. PMID- 3101138 TI - [The molecular genetics of hemophilia]. PMID- 3101139 TI - A technique for treatment of advanced carcinomas of the larynx and hypopharynx using low-megavoltage X-rays. AB - An isocentric three-field technique is described for irradiation of advanced lesions of the larynx and hypopharynx with low-megavoltage (less than or equal to 6 MV) X-rays. The technique has been designed to eliminate field junctures. Two anterior oblique fields and a single posterior field with central spinal cord block are used. With Ellis filters to compensate for tissue deficits, dose homogeneity is assured throughout the upper and lower neck; in particular, the dose at the anterior aspect of the spinal cord is seen to vary by less than 5%. Using this technique, it is possible to deliver 52 Gy to the primary tumor and regional nodes, while restricting the maximum spinal cord dose to 45 Gy. Computed dose distributions are presented and compared with point-dose thermoluminescent measurements made on a humanoid phantom. PMID- 3101140 TI - The results of a series of 963 patients with transitional cell carcinoma of the urinary bladder primarily treated by radical megavoltage X-ray therapy. AB - The results are reported of a large series of patients with transitional cell cancer of the bladder, treated in Edinburgh between 1971 and 1982. Analysis of pre-treatment characteristics for patients with transitional cell bladder cancer showed that tumour category was significantly associated with grade and tumour size. Complete local tumour regression at follow-up cystoscopy was achieved in 45.9% of patients who completed radical megavoltage X-ray therapy. Patients with grade 2 or 3 cancer, a solid cancer or a tumour of less than 8 cm in size had significantly improved complete regression rates. Lasting local tumour control after initial complete regression was better in patients with grade 3 cancer. Complete regression was associated with improved survival for all but patients with T1 cancer. The poorest (uncorrected) survival rates were seen in patients over 79 years of age, those with T4 cancer, an ulcerated cancer, a grade 3 cancer or a tumour of more than 7 cm in size. Metastases were more often seen in patients with grade 3 or T3/T4 cancer. Severe late radiation-related complications were seen in 14.8% of patients. PMID- 3101141 TI - Prognostic indices for bladder cancer: an analysis of patients with transitional cell carcinoma of the bladder primarily treated by radical megavoltage X-ray therapy. AB - A group of 889 patients who completed radical X-ray therapy for transitional cell carcinoma of the bladder during a 12 year period were analysed by a multivariate technique. The patient's age, tumour category, tumour size and haemoglobin level were shown to be independent prognostic covariates. A prognostic index was derived and four prognostic subgroups were identified. The prognostic index could divide patients within each T category into those with good, moderate, fair or poor prognosis. The 5 year actuarial survival rate for patients in the poor prognosis group was 5.8% compared to 69.8% for patients in the good prognosis group. Durable local tumour control after radical radiotherapy was also analysed by a multivariate technique. Tumour category, grade, haemoglobin and urea level were found to be significant covariates. A tumour control index was derived and two groups were identified corresponding to a high probability of lasting local control after radical radiotherapy (47.8% of patients) or a low probability of control (52.2%). PMID- 3101143 TI - Testing a classification instrument for the ambulatory care setting. AB - The purpose of this study was to evaluate the construct validity, generalizability, and interrater reliability of an instrument designed to measure the complexity of nursing care in the ambulatory care setting. The conceptual framework for the development of the classification instrument was adapted from a theory of organizations and is based upon knowledge technology. Previous research using the Delphi methodology delineated 44 activity categories for the classification instrument. These categories were organized under six literature based responsibility areas. The instrument was tested in seven areas of one hospital-based ambulatory care setting. A total of 641 valid patient ratings were used for the analysis. Results indicate the instrument has beginning construct validity and high interrater reliability with training. It is not generalizable across services unless the effect of clinic type on nursing care complexity is considered. PMID- 3101142 TI - Mitomycin C-induced hemolytic uremic syndrome. Six case reports and review of the literature on renal, pulmonary and cardiac side effects of the drug. AB - Six new cases of mitomycin C (MMC)-induced hemolytic uremic syndrome are reported and the literature on renal-, pulmonary- and cardiotoxicity of the drug is reviewed. The number of reports concerning these side effects is still increasing. The incidence of all three side effects will be below 10%, while there appears to be a dose-dependency, with toxicity mainly occurring at cumulative doses of 20-30 mg/m2 or more. Toxicity often develops very sudden and the mortality rate especially of HUS is very high despite supportive care. The pathogenesis of toxicity is still unknown, although for HUS there are indications for a role of circulating immune complexes. The pulmonary toxicity can often be treated by corticosteroids, while the left ventricular cardiac failure can be treated with diuretics. The possible role of oxygen radicals in the development of MMC side effects is mentioned. PMID- 3101144 TI - Sorption of low-level radwaste by Spirulina. AB - The feasibility of using spirulina as adsorbent for the treatment of low-level liquid radwaste is studied. The experimental results indicate that the sorption capacity of spirulina is good for the di- and trivalent metallic ions at pH 3-7, but rather poor for the mono-valent metallic ions and non-metallic ions. Some factors affecting metal ion uptake by spirulina such as the content of detergent, sodium ion in liquid radwaste and the stability of spirulina under gamma irradiation were also investigated. PMID- 3101145 TI - Bioconcentration potential of organic environmental chemicals in humans. AB - A list of environmental chemicals detectable in adipose tissue and/or milk of non occupationally exposed humans is presented. Besides their physiochemical properties (n-octanol/water partition coefficient and water solubility), their acceptable daily intake (ADI) values, production figures, fate in the environment, concentrations in human adipose tissue, and data from total diet studies from market basket investigations are given. Average bioconcentration factors (BCF) of polychlorinated biphenyls (PCBs), 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD), DDT, hexachlorobenzene (HCB), dieldrin, hexachlorocyclohexane isomers (alpha-HCH, beta-HCH, gamma-HCH, delta-HCH), pentachlorophenol (PCP), and 3,5-di-tert-butyl-4-hydroxytoluene (BHT) in human adipose tissue are calculated. The bioconcentration factors (wet wt basis) of these compounds are between 3 and 47 times higher in humans than in rats. The environmental chemicals are divided into three groups in respect to their bioconcentration factors in human adipose tissue: group I, high BCF (greater than 100); group II, medium BCF (10-100); and group III, low BCF (less than 10). The bioconcentration factors are useful for hazard assessment of chemicals to humans. PMID- 3101146 TI - Predictability of human carcinogenicity from animal studies. AB - The predictability of human carcinogenicity from animal studies is discussed. This theme includes both qualitative and quantitative aspects. Recent documentation on evidence for animal carcinogenicity is reviewed. Issues related to carcinogenic potency, high dose-low dose and interspecies extrapolations, as well as carcinogen exposure determination are debated. It is concluded that induction of tumors in well-performed carcinogenicity studies will give evidence of carcinogenic potential for humans. For extrapolation of test results from animals to humans, knowledge of the carcinogenic potency, the dose-response relationship, and the toxicokinetic behavior of the test chemical is essential. Further, comparative studies using newly developed methods to determine carcinogen exposure should be initiated in order to make high dose-low dose and interspecies extrapolations more meaningful. PMID- 3101147 TI - [Management of electron accelerators for radiotherapy. Data as of 31 December 1984]. AB - Several italian radiotherapeutic centers have supplied the data analysed, regarding problems connected with the management of electron accelerators in the years 1982-1983-1984. The data concern 27 out of the 35 accelerators settled in Italy. The average cost of purchase has proved to be of 940 M pounds with an expense of annual allowance of 94 M pounds. We have then analysed the incidences of the allowance of the purchase expenditure of the machine (23%), the allowance of the expenses for the construction of the bunker (22%), the expenses of maintenance of the machine (5%), the cost of the staff (48%) and the cost of the power supply (2%) on the management costs (about pounds 820.000 per each handled patient). The duration of the various phases of the machinery installment, from the purchase to the beginning of the treatment, the charge of work supported in the three considered years, the daily use of the machinery and the problems deriving from days of time out of services due to failures or to periodical maintenance have then been studied. The analysis of the average values of the parameters studied and of the range of their variability allows us to find out the sector in which it is possible, also at present, to intervene in order to ameliorate the employment of a linear accelerator, regarding the costs and the performance. PMID- 3101148 TI - [Axial correction of the limbs in children by the Ilizarov method (2 cases)]. PMID- 3101149 TI - [EEG mapping in partial epilepsy]. AB - Even if mathematic treatment of EEG signals by Fast Fourier Transformation (FFT) in cases of transient epileptic discharges is still controversial, this method has been applied to 21 cases of epileptic partial seizures. Examples are shown, and compared to CT-Scan data. In 17 cases, EEG mapping identified alterations of basic activities upon a definite area. In addition, a focal peak of maximal alterations displacing itself into the limits of the whole epileptogenic area is demonstrated; it is furthermore suggested that the power spectrum keeps, especially during seizures, a peculiar ("combing") morphology, possibly specific of epileptic diseases. PMID- 3101150 TI - [Contribution of sleep EEG to epileptology: evaluation of a year-long study]. AB - In order to confirm, or to deny, the diagnosis of epilepsy a sleep EEG recording as a supplement to the routine EEG investigation has been performed in 229 subjects in 1980 at Saint Paul Center. In 93% of the cases, spontaneous afternoon napping, and in 7% spontaneous nocturnal sleep was studied. Sleep EEG was analysed and correlated to the clinically suspected type of epilepsy. The occurrence of focal or generalized EEG abnormalities, clearly related to the type of epilepsy, confirmed anamnestic and clinical findings in 54% of the cases and gave a more accurate diagnosis in 20% of the cases. Sleep recordings were necessary for the diagnosis of the type of epilepsy in 2% of the cases. PMID- 3101152 TI - [EEG abnormalities of late-onset epilepsy]. AB - Interictal EEG abnormalities were evaluated in 111 epileptic patients in which the first seizure occurred after the age of 18 years. Standard day-time EEG tracings performed prior to and after antiepileptic treatment, and all-night recordings were investigated. Before treatment, waking EEG was normal in 54% of patients. The percentage of normal sleep EEG recordings was only 28.6%. Focal EEG abnormalities were found in 39% of day-time recordings and in 48.6% of sleep recordings, while the percentage of generalized epileptic discharges observed was respectively 7 and 22.8. When considering the category of epilepsy and the etiology, it appears that the primary and secondary generalization of epileptic discharges is reduced with age. PMID- 3101151 TI - [Analysis of the multi-unit activity of the cortex and subcortical structures during paroxysmal discharges and grand mal seizures in the photosensitive baboon]. AB - Cortical and subcortical multiunitary activities (MUA) and EEG were simultaneously recorded in baboons rendered photosensitive by a subconvulsant dose of DL-allylglycine. Intermittent light stimulation (ILS) trains induce in those animals fronto-rolandic (FR) paroxysmal discharges (PDs, constituted as spikes and waves) and grand mal seizures. During the induction of FR PDs by ILS trains, the visual structures (occipital cortex, colliculi superioris, pulvinar) show a significant MUA increase which is not related to the PD spike or wave but is correlated to the flashes. The first structure showing bursts of MUA that frequently precede the PD appearance is the FR cortex. When PDs appear, the bursts are related to the spikes of PDs and are followed by an inhibition during the slow wave. The pontine and mesencephalic reticular formations and the facial nuclei are activated in bursts after the FR PDs have reached a certain amplitude. The thalamic nuclei ventralis lateralis, centrum medianum and lateralis posterior are activated only later, when the FR PDs have reached an even greater amplitude. It is suggested that the activation of visual structures is necessary for FR PD appearance. The secondary pontine and mesencephalic activation could reinforce that of the FR cortex and then the thalamus, and could determine the myoclonus observed in unparalyzed animals. PMID- 3101153 TI - Effects of altering dead space volume on respiration and air sac gases in geese. AB - Dead space volume (VD) was altered in spontaneously breathing, anesthetized geese from values far above (about 115 ml) to those far below (about 3 ml) the normal VD (approximately 40 ml). Respiratory gases were measured in cranial (CrS) and caudal air sacs (CdS) and in blood. The major findings were as follows: Ventilation increased linearly with VD, by increases in tidal volume (VT) at constant breathing rate (fresp); effective parabronchial ventilation, (VT-VD) X fresp, remained constant and so did arterial blood gases. No changes occurred in CrS gas composition. CdS PCO2 declined with decreasing VD, and the respiratory exchange ratio increased, reaching values above unity at the lowest VD. The gas composition in CrS, and particularly its relation to end-expired gas composition, is in agreement with current models of the gas flow pattern in the avian lung. The PCO2 values in CdS are higher than expected by simple models, e.g. by dead space re-inhalation. Neopulmonic gas exchange and incomplete gas mixing are suggested to contribute significantly to the gas composition of CdS. PMID- 3101154 TI - Influence of breathing frequency and tidal volume on cardiac output. AB - The aim of our experiment was to investigate the influence of increasing either breathing frequency or tidal volume on cardiac output (Q), in normocapnia. We measured Q with a CO2 rebreathing method in 6 men and 6 women in the sitting and the supine position, imposing different breathing patterns: in one set of experiments tidal volume was kept constant at 1 L while breathing frequency was randomly changed between 20, 30 and 40 breaths/min; in another breathing frequency was kept constant at 30 breaths/min while tidal volume was randomly altered between 1, 1.5 and 2 L. Switching from open circuit breathing to rebreathing (for measurement of Q) required no change in breathing pattern. From the beginning, CO2 was added to the inspired gas to maintain end-tidal FCO2 at 0.054, so as to obtain steady state conditions throughout the measurements. Q rose significantly when tidal volume was increased (938 ml/L rise in tidal volume when sitting, and 743 ml/L when supine). Breathing frequency had an insignificant effect (213 ml/10 breaths frequency increase when sitting and 142 ml/10 breaths when supine). The greater influence of ventilation on Q when sitting than when supine is best explained by the fact that in the latter position venous return is already high. There are no demonstrable differences in this effect between males and females. PMID- 3101155 TI - Effects of volume and frequency of mechanical ventilation on respiratory activity in humans. AB - This study evaluated the interaction between respiratory chemical drive and non chemical factors related to the frequency and level of thoracic displacement during mechanical ventilation in shaping respiratory activity. Ten normal subjects were artificially hyperventilated with a positive-pressure mechanical respirator to a baseline end-tidal PCO2 of approximately 30 Torr. Thereafter, in separate trials, the end-tidal PCO2 was increased by (a) progressively raising the concentration of CO2 in the inspired gas (FICO2) while holding tidal volume (VT) and breathing frequency (f) constant, (b) lowering f while holding VT and FICO2 constant, and (c) lowering VT while maintaining a constant f and FICO2. Initially, as the PCO2 rose above baseline levels with increases in FICO2, there was no change in inspiratory muscle activity, as measured by the peak inspiratory airway pressure, until the PCO2 reached 40 Torr. This PCO2 threshold for a change in respiratory activity was significantly reduced when the tidal volume or frequency of mechanical ventilation was lowered. These results suggest that non chemical drives related to the frequency and level of thoracic displacement interact with chemical stimuli in shaping respiratory activity. PMID- 3101156 TI - [Gougerot-Sjogren syndrome and Waldenstrom's disease with pulmonary involvement and hypercalcemia]. PMID- 3101157 TI - Both the precursors and the effectors of human lymphokine-activated killer (LAK) cells may belong to T lymphocytes. AB - The present experiments were designed to perform a further investigation of the cell lineage of lymphokine-activated killer (LAK) cells. In the presence of adherent cells both T and not-T cells, separated on the basis of rosette formation with sheep erythrocytes (E rosettes), generated LAK activity after short-term culture in recombinant interleukin-2 in 5 different individuals tested. Since at the termination of the culture more than 98% of cells were T11 positive, it is evident that both LAK precursor and effector cells may belong to the T cell lineage. By applying a culture technique which allows the clonal expansion of virtually all T cells, we further selected and analyzed T cell clones with LAK activity. Under the culture conditions used, LAK clones represented approximately 4% of all proliferating clones. All had cytolytic activity against K562 target cells as well and also released large amounts of gamma-interferon following phytohemagglutinin stimulation. PMID- 3101159 TI - [New class I anti-arrhythmia agents]. PMID- 3101158 TI - Possible model of liver carcinogenesis using inhibitors of NAD+ ADP ribosyl transferase in rats. AB - The response of cellular NAD+ metabolism to DEN and/or ABA and the carcinogenesis of the liver initiated by DEN and ABA were studied in rats. The liver NAD+ level was depleted by an ip injection of 20 mg or 200 mg/kg body weight of DEN. ABA, administered ip at a dose of 600 mg/kg simultaneously with or 4 hours after DEN, prevented the depletion of NAD+ by DEN. These biochemical findings correlated with the changes of conspicuous intranuclear immunofluorescence of poly(ADP ribose), which were studied by immunohistochemistry. When initiated by 20 mg/kg body weight DEN and 600 mg/kg ABA and then processed to selection pressure, the liver was found to be capable of developing hepatocellular carcinomas with or without PB promotion. These results suggest that the inhibition of poly(ADP ribosylation) might lead to irreversible initiation of liver carcinogenesis by DEN in rats. PMID- 3101160 TI - [Duodenal ulcer diseases: physiopathological and therapeutic concepts: evolution, not revolution]. PMID- 3101161 TI - [Epidemiology and prevention of genital infections in women]. PMID- 3101162 TI - Rodilemid therapy in peripheral palsy: a clinical and electrophysiological study. PMID- 3101163 TI - [Incidence of typhoid-paratyphoid infections in Valencia in relation to the levels of drinking water purification and sanitation conditions]. PMID- 3101164 TI - [The neuropsychiatry service in current primary care: an investigation including critical results]. PMID- 3101165 TI - [Descriptive study of the demand for emergency services in a rural area. The Sierra de San Vicente health zone (Toledo)]. PMID- 3101167 TI - Small-intestinal and colonic changes after biliopancreatic bypass for morbid obesity. AB - Morphologic and functional adaptations of the functioning intestine were evaluated in 41 patients before and after biliopancreatic bypass for morbid obesity. This surgical procedure diverts pancreatobiliary secretions via the duodenum and the jejunum into the colon, the remaining small intestine being anastomosed to the stomach after antrectomy. In the proximal ileum there was an 80% increase of the height of villi; the specific activities of maltase, sucrase, and aminopeptidase in brush border membranes remained unaffected, and that of lactase tended to decrease. In the distal ileum villi heights increased only by 58%, and disaccharidase activities (except for maltase) were slightly enhanced. In the colon the mucosa displayed, in some patients, focal appearance of true villi, and brush border enzyme activities increased concomitantly. We conclude that biliopancreatic bypass induces an adaptation of all intestinal segments of the functioning intestine; this adaptation tends to compensate for the shortening of the gut continuity. PMID- 3101166 TI - Duodenal, prepyloric, and combined duodenal/prepyloric ulcer disease: three distinct entities of juxtapyloric ulcer disease? AB - One hundred and seven patients with long-standing and severe chronic juxtapyloric ulcer disease were classified in accordance with the location of the present ulcer and previous ulcers into 1) pure duodenal (DU), 2) pure prepyloric (PU), and 3) combined duodenal/prepyloric (DU/PU) or prepyloric/duodenal (PU/DU) ulcer disease. In a prospective follow-up study over a 3-year period after parietal cell vagotomy (n = 39) or during continuous treatment with cimetidine (n = 62) patients with DU had recurrent ulcers located exclusively to the duodenal bulb and patients with PU, exclusively to the prepyloric region. In patients with DU/PU and PU/DU recurrent ulcers occurred on either side of the pylorus. Basal acid and basal pepsin outputs were higher and bile acid in gastric juice was lower in patients with DU than in those with PU. There are a considerable number of patients who possess features of both duodenal and prepyloric ulcer disease. The clinical outcome of both continuous cimetidine treatment and vagotomy in these patients (DU/PU and PU/DU) was less satisfactory than in pure DU. All patients presenting with active DU should therefore be investigated for evidence of previous prepyloric ulceration. PMID- 3101168 TI - Nucleolus-associated J chains in myeloma cells. AB - Bone marrow aspirates from 10 patients with multiple myeloma (6 IgG myeloma, 3 IgA myeloma, 1 Bence Jones myeloma) were examined for nucleolus-associated localization of J chains. On light microscopy using the PAP method, almost all or a significant number of myeloma cells exhibited intranuclear spots stained with anti-J chains in 3 (IgG myeloma) out of the 8 cases positive for cytoplasmic J chains. In contrast, the nucleus of myeloma cells examined was constantly negative for anti-heavy and -light chains. Immunoelectron microscopically, J chain was identified as dicrete round electron-dense precipitates, corresponding to the whole nucleolus, and as sparsely distributed, small electron-dense deposits in the nucleus. In addition, some connections were found between nuclear and nucleolar electron-dense precipitates. Several possible explanations have been proposed to account for this localization of J chains. PMID- 3101169 TI - Clinical application of the chromogenic assay of factor VIII in haemophilia A, and different variants of von Willebrand's disease. AB - A chromogenic substrate kit for determination of factor VIII activity (COATEST Factor VIII) was compared to a one-stage clotting assay and the correlation was evaluated in different genetic variants of mild and moderate haemophilia A, in severe haemophilia A and in all known variants of von Willebrand's disease. In all these cases a high correlation between the two methods was obtained. A good correlation was also obtained after intranasal administration of DDAVP (1 desamino-8-D-arginine vasopressin) to patients with von Willebrand's disease. The chromogenic substrate method was performed using a microtray technique. PMID- 3101170 TI - Kinetic analysis of interleukin 2 (IL-2) production and expression of IL-2 receptors by uraemic and normal lymphocytes. AB - The in vitro immune response of lymphocytes from uraemic patients was studied by comparing the in vitro kinetics of interleukin 2 (IL-2) production, the mitogen induced proliferative response, and the expression of IL-2 receptors by T lymphocytes. The IL-2 production in 26 uraemic cell cultures decreased significantly after 48 h of stimulation with mitogen compared with that of 24 control cultures. The lymphocyte responses to phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) increased linearly with time, but the responses of the uraemic cell cultures were significantly lower than those of the control cultures. The relative numbers of cells double-stained for both Tac (IL-2 receptor)/HLA-DR or Tac/Leu 2 were significantly increased in the uraemic cultures as compared with the control cultures at 48 and 72 h. A similar, but not significant, trend was also demonstrated for uraemic cells positive for Tac/Leu 3. These findings were also seen in uraemic lymphocyte cultures supplemented with exogenous IL-2. Thus, the IL-2 production of uraemic lymphocytes seems to be exhausted more rapidly than that of normal lymphocytes, and there is no evidence that the poor proliferative response of uraemic lymphocytes is due to a decreased relative number of cells positive for IL-2 receptors. PMID- 3101171 TI - Monitoring fluid absorption during TURP by marking the irrigating solution with ethanol. AB - Ethanol has been evaluated as a marker of the irrigating fluid during TURP. In nine patients mannitol served as a reference substance (2% ethanol in 5% mannitol) and it could be verified that ethanol enters the body as a result of irrigating fluid absorption. Ethanol is instantly and easily demonstrated in the patient's expired breath with an Alcolmeter. In four healthy volunteers a 500 ml intravenous infusion of the irrigating fluid was given to imitate absorption. These experiments showed that very small amounts gave significant concentrations of ethanol in expired breath and that there was a distinct fall in expired ethanol as soon as the infusion was stopped. Thus marking the irrigating fluid with ethanol is a simple method which may be used to indicate absorption, to follow its course and to tell if preventive steps taken against further absorption are effective. PMID- 3101172 TI - Amino acid sequence of the variable region of an unusual lambda-type human Bence Jones protein (Lee). AB - The variable portion of a human lambda-type Bence Jones protein (Lee) has been prepared by limited tryptic digestion. Its amino acid sequence is determined from analysis of tryptic peptides, CNBr cleavage fragments prepared from the reduced aminoethylated protein. Peptides are aligned by homology to other lambda-type proteins. The Lee L-chain has an unusual extension of two amino acid residues (Val-Thr) at the N-terminus. An idiotypic antibody of Lee can react with two other lambda-type Bence Jones proteins, Meg (V lambda IV) and Cap (V lambda III). Application of the principle of Chou and Fasman to the sequence data indicates that two portions on the surface of the V-region have identical secondary structures similar to the portions of the Meg and Cap lambda-chains. This appears to relate to the idiotypic similarities of the three proteins. PMID- 3101173 TI - Levels of some organochlorine residues in blood of patients with arteriosclerotic disease. AB - This study aims to elucidate if any association exists between the development of arteriosclerotic disease and contamination of the internal human environment with certain organochlorine compounds (OCCs). For this purpose the levels of DDT isomers and their metabolites, and of lindane, dieldrin, heptachlor epoxide, and polychlorinated biphenyls (PCBs) were determined in blood serum of 11 patients suffering from slight to moderate (group A), and 24 patients with moderate to severe (group B), arteriosclerotic lesions. The control group consisted of 27 patients with no obvious manifestations of arteriosclerosis. The main findings of the study in comparison with the control group were: Mean OCC residue levels in blood were slightly higher in group A and markedly so in group B; The variability and the extent of departure from normality of distributions of organochlorine insecticides (OCIs) decreased, whereas those of PCBs increased, in arteriosclerotic patients (more markedly in group B); The degree of correlation between blood serum levels of various OCCs was elevated in group A and low in group B. It remains to be ascertained whether changes in the body burden of OCCs are primary, resulting from increased exposure to and absorption of these compounds which thus contribute to the development of arteriosclerosis, or are of secondary origin, due to inhibition of xenobiotic metabolism caused by interference of the arteriosclerotic process with the functions of drug metabolizing enzymes of liver microsomes. PMID- 3101174 TI - Chlorinated insecticides and PCBs in Asteroidea and Holothuroidea species from Rijeka Bay, Yugoslavia. AB - For an evaluation of the extent of pollution in Rijeka Bay, Yugoslavia by chlorinated hydrocarbons an investigation of levels in sediments and the most abundant benthic organisms (Asteroidea and Holothuroidea species) has been carried out. Samples were collected at several stations in October 1981. The concentrations of chlorinated insecticides and polychlorinated biphenyls (PCBs) in Asteroidea species were from 0.5 to 46.0 micrograms kg-1 for DDTtotal, and from 2.5 to 435 micrograms kg-1 (wet weight) for PCBs. For the PCBs in Holothuroidea species the values ranged from 4.4 to 37.2 micrograms kg-1 and for DDTtotal from 0.9 to 48.5 micrograms kg-1. The contamination of Asteroidea and Holothuroidea samples from Rijeka Bay with persistent chlorinated hydrocarbons was compared with other data for the same species from other parts of the world. Accumulation of chlorinated hydrocarbons by Asteroidea and Holothuroidea species from sediments of Rijeka Bay is discussed with respect to concentration factors (CF). The highest CF (70.0) (dry biota/dry sediment) was obtained for the intestines of Asteroidea species for PCBs and a value of only 2.6 was obtained for DDTtotal for the skin and muscle of Holothuroidea species. The relatively low bioaccumulation of PCBs and DDTs from sediments in the Rijeka Bay by the Asteroidea and Holothuroidea species is reassuring, because of the problem of dredging and ocean dumping of sediments polluted with persistent chlorinated hydrocarbons. PMID- 3101175 TI - Diurnal expression of transducin mRNA and translocation of transducin in rods of rat retina. AB - The messenger RNA (mRNA) that encodes alpha subunit of the guanosine triphosphate binding protein transducin (T alpha) and T alpha immunoreactivity were localized and measured in the rat retina during the light-dark cycle with in situ hybridization and immunohistochemistry. Both T alpha mRNA and T alpha immunoreactivity were observed only in photoreceptors. Within the photoreceptor T alpha mRNA was present primarily in the inner segments and to a lesser extent in the outer nuclear layer at all times during the day and night. However, the distribution of T alpha immunoreactivity varied profoundly with the light-dark cycle; during the day, T alpha immunoreactivity was highest in the inner segments, and at night the outer segments were more immunoreactive. The amounts of T alpha mRNA and T alpha immunoreactivity also depended on the light-dark cycle. Levels of T alpha mRNA were high immediately before and after lights on; levels were low for the rest of the light-dark cycle. During the day, T alpha immunoreactivity increased in the inner segments following the increase in T alpha mRNA. After the lights were turned off, T alpha immunoreactivity decreased in the inner segments and increased in the outer segments. Thus, it appears that T alpha is synthesized in the inner segments after a morning increase in T alpha mRNA. Newly synthesized T alpha remains in the inner segments until it is transported to the outer segments at night, where it may be involved in the increase in the sensitivity of photoreceptor rods at night. PMID- 3101176 TI - Lysosphingolipids inhibit protein kinase C: implications for the sphingolipidoses. AB - Lysosphingolipids potently and reversibly inhibited protein kinase C activity and binding of phorbol dibutyrate in vitro and in human platelets. As with activation of protein kinase C by phosphatidylserine and sn-1,2-diacylglycerol, inhibition was subject to surface dilution. Accordingly, inhibition in mixed micelle assays was dependent on the molar percentage of lysosphingolipids rather than the bulk concentration. Lysosphingolipids inhibited protein kinase C activity at molar percentages similar to those required for activation by phosphatidylserine and sn 1,2-diacylglycerol. Since lysosphingolipids accumulate in Krabbe's disease, Gaucher's disease, and other sphingolipidoses, the hypothesis that lysosphingolipid inhibition of protein kinase C represents the missing functional link between the accumulation of sphingolipids and the pathogenesis of these disorders appears to unify existing data. The accumulation of lysosphingolipids would cause progressive dysfunction of signal transduction mechanisms vital for neural transmission, differentiation, development, and proliferation and would eventually lead to cell death. PMID- 3101177 TI - Debate over emergence of human tooth pattern. PMID- 3101178 TI - Cytochrome P-450--catalyzed formation of delta 4-VPA, a toxic metabolite of valproic acid. AB - Liver damage induced by the antiepileptic drug valproic acid (VPA) is believed to be mediated by an unsaturated metabolite of the drug, delta 4-VPA. In studies of the biological origin of this hepatotoxic compound, it was found that liver microsomes from phenobarbital-treated rats catalyzed the desaturation of VPA to delta 4-VPA. Indirect evidence suggested that cytochrome P-450 was the responsible enzyme, a conclusion that was verified by studies with a purified and reconstituted form of the hemoprotein, which catalyzed the oxidation of VPA to 4- and 5-hydroxyvalproic acid and to delta 4-VPA. Desaturation of a nonactivated alkyl substituent represents a novel metabolic function of cytochrome P-450 and probably proceeds via the conversion of substrate to a transient free radical intermediate, which partitions between recombination (alcohol formation) and elimination (olefin production) pathways. These findings have broad implications with respect to the metabolic generation of olefins and may explain the increased hepatotoxic potential of VPA when it is administered in combination with potent enzyme-inducing anticonvulsants such as phenobarbital. PMID- 3101179 TI - [Changes in society and the rights of man]. PMID- 3101180 TI - [The rights of man--a serious and decisive pledge]. PMID- 3101181 TI - [The rights of man: new questions for health professionals]. PMID- 3101182 TI - [The rights of man--the action and compromise]. PMID- 3101183 TI - [The right to life and the quality of life]. PMID- 3101184 TI - [The right to give life]. PMID- 3101185 TI - [The family]. PMID- 3101186 TI - [The child and its rights]. PMID- 3101187 TI - [The right to health]. PMID- 3101188 TI - [Nursing personnel and their responsibility]. PMID- 3101190 TI - [The right to human contact from life till death]. PMID- 3101189 TI - [The rights of patients and the family]. PMID- 3101191 TI - [The offense to mental dignity, physical integrity and individual freedom...]. PMID- 3101193 TI - [The right to a professional education]. PMID- 3101192 TI - [The rights of health personnel]. PMID- 3101194 TI - [Conscientious objection]. PMID- 3101195 TI - [The right of association and the right to belong to a professional association]. PMID- 3101196 TI - [The rights to security in the exercise of a profession]. PMID- 3101197 TI - [The rights of health personnel]. PMID- 3101198 TI - [Employment conditions and the professional life of nursing personnel]. PMID- 3101199 TI - [Too old to dream? Nursing in Europe 1986]. PMID- 3101200 TI - [Synthesis and future prospects]. PMID- 3101201 TI - Respiratory insufficiency in adult-onset acid maltase deficiency. AB - Although the adult form of acid maltase deficiency is characterized by weakness of the limb girdle muscles, weakness of the respiratory muscles out of proportion to that of the limb muscles may make the diagnosis less obvious. We present four patients aged 35 to 57 with respiratory muscle weakness associated with signs of cor pulmonale and symptoms of alveolar hypoventilation. Each had symptoms of fatigue, hypersomnolence, morning headache, and orthopnea, the cause of which was misdiagnosed. The key to diagnosis was paradoxic abdominal motion on inspiration. This finding, consistent with diaphragmatic paralysis, led to neurologic evaluation, electromyographic examination, and muscle biopsy to confirm the diagnosis. The symptoms of alveolar hypoventilation were reversed with chronic nocturnal ventilation, which assisted in rehabilitating some patients. PMID- 3101202 TI - Changes in end tidal CO2 and arterial blood gas levels after release of tourniquet. AB - We studied nine healthy adult patients having orthopedic surgical procedures requiring the use of a tourniquet under general anesthesia with controlled mechanical ventilation to determine changes in end tidal CO2 (EtCO2) and arterial blood gas values after tourniquet deflation. After deflation of the tourniquet, EtCO2 and PaCO2 increased maximally within one minute; EtCO2 returned to baseline at a mean time of 13 minutes 7 seconds +/- 5 minutes 17 seconds, while PaCO2 was still above baseline when the study was terminated. The pH level decreased significantly, with the maximal fall occurring within four minutes; it remained below baseline when the study was terminated. The PaO2 level decreased and the bicarbonate level increased, though neither change was statistically significant. After tourniquet release, hyperventilation may be indicated to facilitate the return of PaCO2 and pH levels to baseline; in patients whose acid-base status is compromised by preexisting disease, PaCO2 and pH should be monitored closely. The PaCO2 level could be predicted by monitoring the EtCO2 level. PMID- 3101203 TI - Dilatation of a stenotic esophageal segment containing a diverticulum. AB - Dilatation of stenotic esophageal lesions containing diverticula has not been previously addressed in the literature. We report a case of successful dilatation. With increased intraluminal pressures, there is an increased risk of esophageal rupture in this situation. We suggest that dilatation can be safely done in this situation, and we recommend the use of a Gruntzig balloon catheter because of its unique properties. PMID- 3101204 TI - Isolated vocal cord hematoma in a child with severe factor VIII deficiency. AB - We have reported the first case of isolated submucosal hematoma of the true vocal cord in a hemophilic patient. He was managed with factor VIII replacement therapy as an outpatient for five consecutive days, without complication. Similar but more serious cases usually require more aggressive intervention by the pediatrician and the otolaryngologist. PMID- 3101205 TI - [Role of Pseudomonas aeruginosa in the pathogenesis of acute destructive processes in the lungs]. PMID- 3101206 TI - Immunisation and viral disease in Transkei. AB - An attempt was made in 1982 by the Department of Health, Transkei, to improve the vaccination programme by means of an extended Immunisation programme (EIP). Twelve hospitals were involved in the EIP at the beginning of July 1982, but only Rietvlei Hospital in the Umzimkulu district managed to complete three doses of the diphtheria, whooping cough, tetanus, and poliomyelitis vaccines, and to submit a partial report to the Central Unit. This report covered 11 locations and a total of 1,957 children in the under-5-year age group. The current system of notification for the monitoring of viral disease in Transkei is also commented on. Evaluation of the official notifications from 1971 to 1983 shows that viral disease represented only 2.7% of the diseases with public health impact in Transkei, and that measles and poliomyelitis are prevalent. PMID- 3101207 TI - Gaucher's disease in the Cape coloured population of the RSA, including a family with 5 affected siblings. AB - Nine Cape Coloured children from 4 families with severe non-neuropathic Gaucher's disease are documented. The diagnosis was confirmed histologically in the bone marrow, spleen and liver, and by serum acid phosphatase and leucocyte beta glucosidase assays. This represents a minimum prevalence for Gaucher's disease of 1 in 247,350 in this population and an approximate genetic carrier rate of 1 in 230 for the abnormal gene. A family with 5 affected siblings is recorded. The severe early clinical expression documented in these coloured patients is similar to that described in the Afrikaner population and differs from the less severe expression of Gaucher's disease in the South African Ashkenazi Jewish population. Gaucher's disease in the Cape Coloured population presents with a precocious onset, causes severe complications and progresses rapidly. PMID- 3101209 TI - Transverse myelitis caused by schistosomiasis during pregnancy. A case report. AB - A rare case of transverse myelitis caused by schistosomiasis of the spinal cord during pregnancy is presented. The diagnosis and treatment are discussed. PMID- 3101208 TI - An enzyme-linked immunosorbent assay using adsorbed mycobacterial sonicates for the serodiagnosis of tuberculosis. AB - Sera from 123 patients with confirmed tuberculosis and 576 patients with other non-mycobacterial diseases were tested for antibodies to an adsorbed mycobacterial sonicate antigen employing an enzyme-linked immunosorbent assay. The results show significant differences in IgG levels between sera from tuberculosis patients and controls. The results of delayed hypersensitivity skin test reactions to purified protein derivative in both the patient and control groups were unrelated to antibody levels. The assay was able to detect antibodies for at least 4 months after diagnosis and treatment. Patients diagnosed as having tuberculosis 7 months or more before being tested did not demonstrate increased antibody levels. The assay could be useful not only as a screening technique for diagnosing tuberculosis in an immunised population but also as a means of monitoring antituberculosis treatment. PMID- 3101210 TI - [Erythrocyte sensitization in a drug addict]. PMID- 3101211 TI - The National Burn Information Exchange. The use of a national burn registry to evaluate and address the burn problem. AB - The NBIE, a voluntary registry of specialized burn-care facilities that was founded in 1964, currently has 50 active participants representing 35 per cent of the nation's hospital beds for burned patients. Participating physicians submit information on the initial hospitalization of emergent and acute burn patients and, separately, on the reconstruction process for these patients. As of January 1986, a total of 94,594 patient's data are on file from 130 hospitals; 13,671 of these are reconstructive and 80,923 emergent and acute admissions. Information concerning new patients is submitted at a rate of about 6000 patients annually. The data are analyzed using INQUIRE, an original data retrieval system. Data on treatment methods and outcome have been used to establish baseline standards for the burned patient's care and survival. In addition, these data have been used to document institutional differences in mortality rates and indicate methods used by the more successful hospitals. The data also are being used to describe the long process of recovery from severe burns and to monitor changes in outcomes of burn accidents continually. The result of these analyses has been documentation of an overall improvement in survival and decline in hospitalization times at all levels of burn severity. Data also can be used with institution-specific data to look at organizational variables affecting survival. Use of this epidemiologic data allows prevention projects to be targeted at the groups at greatest risk. A newer application looks at the equity of the HCFA prospective payment system based on the DRGs assigned to burn severity. The NBIE is an example of how a voluntary, national registry, properly computerized and effectively managed, can contribute to resolving the problem it was established to study. The NBIE has been useful in increasing the understanding of health professionals and government decision makers of a complicated disease process. It has had a direct effect on the quality of patient care and on the process of controlling the incidence of burn injuries. PMID- 3101212 TI - Systemic antibiotic treatment in burned patients. AB - Systemic antibiotics are a valuable therapeutic modality in the burned patient when properly used. Injudicious use, however, may not only fail to be beneficial to the patient but also may produce harmful effects--either through direct toxicity or by contributing to the emergence of resistant strains of micro organisms. General guidelines and principles for systemic antibiotic use include the following: The burned patient, despite all efforts, will be exposed to microorganisms. No single agent or combination of agents can destroy all the organisms to which the burned patient is exposed. Treatment involves first identifying the organism responsible for clinical sepsis, then choosing appropriate agents. Combinations of antibiotics are not always synergistic or even additive in effect. Multiagent therapy may have the untoward effect of predisposing to superinfection by yeast, fungi, or resistant organisms. Antibiotics should be used for a long enough period to produce an effect, but not long enough to allow for emergence of opportunistic or resistant organisms. Dosages must be adjusted based on serum concentrations when serum assays are available. In general prophylactic systemic antibiotics are indicated in only a few clinical situations including the immediate preoperative and postoperative periods associated with excision and autografting, and possibly in the early phases of burns in children. The penetration of systemic antibiotics into burn eschar remains an area not fully studied; hence, they cannot be the only therapeutic modality used to treat burn wound infection. Systemic dosages of antibiotics in burns will require alteration depending on the clinical status of the patient. The choice of agent requires a thorough knowledge of side effects, toxicity, and potential benefit. Above all, active surveillance and monitoring of the burned patient and the environment in which he or she is being treated is mandatory for effective treatment. The increasing number of new antimicrobial agents has presented a new dilemma to the practicing clinician because many of these agents have not been evaluated thoroughly in the burned population. With further studies, the armamentarium of the burn treatment team will inevitably increase. It is in this manner only that so many of the unanswered questions will be solved, and that infection will start to decline as the major cause of death in the burned population. PMID- 3101214 TI - [Heavy particle radiotherapy at the University of California Lawrence Berkeley Laboratory. Clinical studies by the Northern California Oncology Group]. AB - At the university of California Lawrence Berkeley Laboratory, patients have been irradiated for 10 years with heavy ions (He, C, Ne, Si). Due to the biologic efficacy of this type of radiation as well as the possibility of a precise dose application, the tumors can be irradiated with very high doses without exposing the surrounding tissues. The experience gained in the treatment of more than 800 patients is presented. It shows that this radiation can be used to localize tumors situated near to particularly radiosensitive organs such as skull base, paraspinal region, and the eye. PMID- 3101213 TI - [Thermoluminescent dosimetry studies on absorptive behavior of bones without and with metal implants]. AB - The absorption and scattering in bones with and without metal implants (femur, humerus, ramus mandibulae) is investigated in an automatic water phantom by means of thermoluminescent dosimetry, a semi-conductor detector, and the ionization measuring chamber for different types of radiation. In case of Co-60 gamma radiation a strong back scattering is observed which increases the dose by up to 50% at the side of entry of radiation and reduces the dose at the other side by equally up to 50%. If ultrahard X-radiation of 9 MeV is used under the same conditions, there is considerably less back scattering and an increased forward scattering. Electron radiation of 10 MeV causes a considerable dose increase of up to 45% due to back scattering. PMID- 3101215 TI - Glucose and urea kinetics in patients with early and advanced gastrointestinal cancer: the response to glucose infusion, parenteral feeding, and surgical resection. AB - We isotopically determined rates of glucose turnover, urea turnover, and glucose oxidation in normal volunteers (n = 16), patients with early gastrointestinal (EGI) cancer (n = 6), and patients with advanced gastrointestinal (AGI) cancer (n = 10). Studies were performed in the basal state, during glucose infusion (4 mg/kg/min), and during total parenteral feeding (patients with AGI cancer only). Patients with early stages of the disease were also studied 2 to 3 months after resection of the cancer. Basal rates of glucose turnover were similar in volunteers and in patients with EGI cancer (13.9 +/- 0.3 mumol/kg/min and 13.3 +/ 0.2 mumol/kg/min, respectively) but were significantly higher in patients with AGI cancer (17.6 +/- 1.4 mumol/kg/min). Glucose infusion resulted in significantly less suppression of endogenous production in both patient groups than that seen in the volunteers (76% +/- 6% for EGI group, 69% +/- 7% for AGI group, and 94% +/- 4% for volunteers). The rate of glucose oxidation increased progressively in proportion to the tumor bulk. In the volunteers the percent of VCO2 from glucose oxidation was 23.9% +/- 0.7%, and in EGI and AGI groups the values were 32.8% +/- 2.0% and 43.0% +/- 3.0%, respectively. After curative resection of the cancer, glucose utilization decreased significantly (p less than 0.05). The rate of urea turnover was significantly higher in the AGI group (8.4 +/- 1.0 mumol/kg/min) in comparison with the volunteer group value of 5.9 +/- 0.6 mumol/kg/min (p less than 0.03). Glucose infusion resulted in a significant suppression of urea turnover in the volunteers (p less than 0.02), but in the AGI group glucose infusion did not induce a statistically significant decrease. We conclude from these studies that the presence of even a small, potentially curable gastrointestinal cancer is associated with a loss of the normal host regulatory mechanisms designed to conserve body resources; this effect is more marked as the tumor bulk increases; increasing tumor bulk effects a progressive increase in glucose utilization and in protein breakdown. PMID- 3101216 TI - Plasticity in algae. AB - Unicellular planktonic algae show considerable developmental plasticity in relation to mean cell size and the fraction of the cell volume occupied by various organelles. Changes in cell size and composition in relation to variations in the supply of light and nutrient solutes have been partially characterized with respect to the signals which regulate the changes, and in terms of the possible significance of the changes in maximizing growth rate under different resource-limited conditions. Less is known of the mechanisms by which the signals lead to the observed phenotypic effects. Multicellular attached macroalgae, whether acellular or multicellular, rhizophytic or haptophytic, have greater scope for phenotypic modification of morphology than do microalgae, in addition to the possibility of biochemical (compositional) changes. In addition to biochemical changes in response to variations in the ratio of availability of various resources (photons, N, P) there are also structural changes; significant here is the increased occurrence of (often colourless) hairs in haptophytes and (probably) of enhanced rhizoid development in rhizophytes. Many of the changes in morphology and physiology of macroalgae in response to changes in photon and nutrient supply have analogies in the behaviour of vascular plants (especially of aquatic vascular plants). PMID- 3101217 TI - Precautions for health care workers in the care of AIDS patients. PMID- 3101218 TI - Specificity of the thrombin-induced release of tissue plasminogen activator from cultured human endothelial cells. AB - The addition of thrombin (9 nM) to primary cultures of human endothelial cells induces a 6- to 7-fold increase in the rate of release of tissue plasminogen activator (tPA). Several other serine proteases which specifically interact with endothelial cells were also analyzed for their effect on tPA release. Gamma thrombin, an autocatalytic product of alpha-thrombin, promoted tPA release but was less effective than alpha-thrombin. A maximum increase of 5.5-fold was observed, although a concentration of gamma-thrombin 20 times greater than alpha thrombin was required. The response to Factor Xa was similar to alpha-thrombin, although the stimulation was significantly reduced by the addition of hirudin or DAPA suggesting that prothrombin activation was occurring. The simultaneous addition of prothrombin with Factor Xa resulted in enhanced tPA release equal to that observed with an equimolar concentration of active alpha-thrombin. Thus, under these conditions, Factor Xa-cell surface mediated activation of prothrombin can lead to a secondary effect resulting from cell-thrombin interaction. Activated protein C, which has been implicated as a profibrinolytic agent, was also tested. No change in tPA release occurred after the addition of up to 325 nM activated protein C in the presence or absence of proteins. Factor IXa and plasmin were also ineffective. The effect of thrombin on the endothelial cell derived plasminogen activator specific inhibitor was also studied. Thrombin produced a small but variable release of the inhibitor with an increase of less than twice that of non-thrombin treated controls. PMID- 3101219 TI - Abnormal properties and behaviors of antithrombin III found in a thrombophilic patient: defective biological functions and dissimilar antigenic determinants. AB - Abnormal properties of antithrombin III have been found in a 55-year-old male who has been thrombophilic over the last seven years. They are characterized by defective inhibition of thrombin and activated blood coagulation factor X, reduced affinity to heparin and partial immunological identity with the normal molecule. The antithrombin III molecule, however, preserves a single-chain structure and an apparently identical molecular weight with that of the normal molecule. It is, thus, very unlikely that the impaired functions of antithrombin III in the patient's plasma are induced by possible proteolytic modifications of the molecule by thrombin or other related activated blood coagulation factors. Since no other members of his immediate family have been found to be affected, the abnormality may be acquired rather than genetically determined, although further investigation is necessary for the elucidation of the abnormality of the molecule. PMID- 3101220 TI - Aggregation of washed platelets from non-anticoagulated human blood is not reversible. AB - Most of the knowledge acquired on platelet function and biochemistry has been obtained from platelets prepared from blood anticoagulated with sodium citrate. Using washed platelets from human blood (PNB) to which no anticoagulants were added, we report on responses not observed with platelets prepared from citrate anticoagulated blood. Native blood was passed rapidly (within 5 min of venepuncture) through a Sephadex G-25/G-50 column to remove divalent ions and thus prevent coagulation. Platelets were separated from the gel-filtered blood by differential centrifugation. Responses of PNB to thrombin, collagen, calcium ionophore, ristocetin, release of 14C-5hydroxytryptamine and beta thromboglobulin, and generation of thromboxane A2 were similar to those observed for citrated platelets. Comparison of PNB with thrombin-treated platelets, which demonstrate an increase of platelet factor 3 activity, a reduction of the adenylate energy charge and an impairment of clot retraction, indicated the absence of platelet activation. Unlike citrated platelets, however, aggregation of PNB in response to ADP was irreversible in the presence of Ca2+ and fibrinogen, even at concentrations as low as 0.2 microM ADP, with aggregation taking up to 25 times longer to reach the same extent of aggregation as for citrated platelets. PNB did not aggregate to epinephrine even in the presence of Ca2+ and fibrinogen. Sodium citrate impaired ADP-induced aggregation and clot retraction of PNB. Thus citrate affects platelet function and may cause changes resulting in the unphysiological behaviour and responses of platelets. PMID- 3101222 TI - Purification and characterization of single-chain urokinase-type plasminogen activator (pro-urokinase) from human A431 cells. AB - A single-chain urokinase-type plasminogen activator (A431sc-uPA) was purified approximately 18,000-fold from A431 human epidermoid carcinoma cell supernatants by monoclonal antibody immunoaffinity chromatography on 5B4-agarose and ion exchange FPLC (overall yield 63%). More than 100 micrograms of A431sc-uPA can be recovered per liter of supernatant. The product is homogeneous by SDS-PAGE and reverse phase FPLC analysis while two main isoelectric forms of pI 9.05 and pI 9.20 were observed by IEF. SDS-PAGE in reducing and non-reducing conditions, Western blot analysis and zymography showed that A431sc-uPA is a single-chain protein of about 50,000 Mr immunologically related to urokinase (uPA) and distinct from tissue plasminogen activator (tPA). The N-terminal aminoacid sequence of A431sc-uPA (27 residues) is identical to that of human kidney single chain uPA. A431sc-uPA does not incorporate 3H-diisopropylfluorophosphate and is virtually inactive on the synthetic substrate S-2444. Plasmin treatment converts A431sc-uPA into a two-chain active form with a fibrinolytic specific activity of 123,000 I. U./mg. PMID- 3101221 TI - The diurnal increase in euglobulin fibrinolytic activity in women using oral contraceptives and in normal women, and the generation of intrinsic fibrinolytic activity. AB - The diurnal fluctuations in plasma euglobulin fibrinolytic activity in women on oral contraceptives and in normal women showed similar patterns of increase. Following inactivation of inhibitors by flufenamate the individual increases and the evening levels did not differ. The diurnal increase was related to an increase in extrinsic (tissue-type) plasminogen activator (t-PA) activity, which contributes little to the total activity of the euglobulin fraction but induces an activation of the intrinsic system. PMID- 3101223 TI - Effect of fibronectin and von Willebrand factor on the adhesion of human fixed washed platelets to collagen immobilized beads. AB - The adhesion of human fixed washed platelets (FWP) to collagen was measured using collagen immobilized beads. The addition of normal plasma or severe von Willebrand disease (VWD) plasma to FWP decreased the adhesion, suggesting the presence of some inhibitors of platelet adhesion in human plasma. Although the adhesion of FWP in severe VWD plasma was not different from that of FWP in normal plasma, the addition of purified von Willebrand factor (vWF, 1-2 mu/ml ristocetin cofactor) to FWP in buffer increased the FWP adhesion at higher flow rates, and the percent of adhesion in the absence of vWF was 10% (collagen 500 micrograms) and 30% (collagen 1,000 micrograms) of that in the presence of vWF at 10 ml/min. The enhancing effect of the vWF on FWP adhesion was also observed by pretreatment of the collagen column with vWF suggesting the important role of bound vWF to the collagen; adhesion 72% to the collagen column (1,600 micrograms) treated with vWF and 16% to the collagen column without the pretreatment at 10 ml/min. The promoting effect of vWF was also present in some commercial factor VIII preparations which had no large or intermediate multimers of vWF antigen. The adhesion of FWP was inhibited by fibronectin (FN) and the binding of ristocetin cofactor (vWF:RCo) to collagen fiber was also inhibited by FN; bound vWF:RCo to 50 micrograms/ml collagen in the absence or presence of 125 micrograms/ml FN were 60% and 8% respectively. It is suggested that vWF, even small multimer of vWF:Ag, is involved in the initial platelet-collagen interaction at high flow rates, while plasma FN acts as one of anti-adhesion factor. PMID- 3101224 TI - [Gonadotropin treatment of infertile women]. PMID- 3101225 TI - [Heart and lung transplantation in Eisenmenger's syndrome]. PMID- 3101226 TI - [Nursing and treatment programs. Do we need them?]. PMID- 3101227 TI - Medicare and Medicaid payment strategies for health care providers. PMID- 3101228 TI - Hospital participation in alternative payment: developing a DRG-based system. PMID- 3101229 TI - Development of long-term care insurance products. PMID- 3101230 TI - Toxic peptides from freshwater cyanobacteria (blue-green algae). I. Isolation, purification and characterization of peptides from Microcystis aeruginosa and Anabaena flos-aquae. AB - Toxic peptides from two European Microcystis aeruginosa and one Canadian Anabaena flos-aquae species of freshwater cyanobacteria (blue-green algae) were purified by high performance liquid chromatography (HPLC) and examined by amino acid analysis and mass spectrometry. A toxic fraction from a butanol/methanol extract of toxic lyophilized cells was separated by G-25 gel filtration and purified by HPLC using a C-18 semi-preparative Column. A toxic peak with the same elution time was detected for each of the three toxic cyanobacteria. The desalted purified toxins (i.p. LD50 in mice, 50 micrograms/kg) caused signs of poisoning identical with previous literature reports of hepatotoxic peptides from Microcystis. On hydrolysis and amino acid analysis all three toxins showed a similar profile, consisting of equimolar amounts of glutamic acid, alanine, arginine and leucine. beta-methyl aspartic acid was identified in all of the toxic peptides. The fast atom bombardment mass spectra of the toxins indicated the molecular weight to be 994 for all the peptides. The absence of sequence ions in their corresponding fast atom bombardment mass spectra indicated the peptides to be cyclic. PMID- 3101231 TI - Trial of isolation of a virus from sera of patients with Kawasaki disease. AB - We tried to isolate pathogenic viruses from specimens of patients with Kawasaki disease. Blood clots and sera, spinal fluid, throat swabs, stool and urine from 24 patients with Kawasaki disease were studied. The specimens were inoculated into HEL cells and Vero cells. The cells were observed for one month, but no cytopathic effect (CPE) occurred. Blind passage was performed, but no degeneration of the second series of cells was observed. Fluorescent antibody indirect methods to determine viral antigens in cells inoculated with patients' specimens was also negative. PMID- 3101232 TI - Minor and trace sterols from marine invertebrates 56. Novel coprostanols from the marine sponge Petrosia ficiformis. AB - Twelve stanols possessing the rare 5 beta-dihydro nucleus have been isolated from the marine sponge Petrosia ficiformis. These stanols have not previously been encountered in any samples of P. ficiformis which we have examined and appear to be the result of bacterial metabolism of the endogenous sponge sterols. PMID- 3101233 TI - Cerebrovascular ischemia associated with lupus anticoagulant. AB - The lupus anticoagulant, an acquired circulating serum gamma-globulin, prolongs all phospholipid-dependent coagulation tests. Recent associations of the lupus anticoagulant and focal cerebral and/or ocular ischemia have been made. We present 5 cases of lupus anticoagulant-associated cerebrovascular ischemia and review all reported cases for the first time. Clinical spectra, cerebral angiographic findings, associated conditions, and response to therapy are presented. Typical features include a relatively young age (mean 39 years), female preponderance, transient ischemic attacks (including amaurosis fugax) or stroke, and normal or large vessel occlusions on angiography. Commonly associated conditions were systemic lupus erythematosus (34%), noncerebral venous thrombosis (31%), hypertension (28%), false-positive VDRL (28%), and spontaneous abortions (22%). Four of our 5 patients (all without systemic lupus erythematosus) and 11 of the 20 (55%) patients in the literature without systemic lupus erythematosus had other definite stroke risk factors coexisting. Response to therapy was highly variable, with no clear beneficial effect of corticosteroids. PMID- 3101234 TI - [10 years in the Swiss dental industry. Use of dental materials in Switzerland in the 80s]. PMID- 3101235 TI - [Nebucid 840, a useful instrument for hand disinfection in the dental office]. PMID- 3101236 TI - [Treatment of jaw and facial bone injuries in changing times]. PMID- 3101237 TI - Analysis of the thymic microenvironment by monoclonal antibodies with special reference to thymic nurse cells. AB - Two hybridoma cell lines secreting monoclonal antibodies against stromal tissues of mouse thymus were produced using the spleen cells of BALB/C mice immunized with newborn thymic homogenate of C57BL/6 mice emulsified in Freund's complete adjuvant. The monoclonal antibody Th-3 reacted with stromal cells in the thymic cortex and the monoclonal antibody Th-4 reacted with stromal cells in the thymic medulla. The stromal cells revealed by Th-3 showed a meshwork structure in the cortex, and formed a monolayered border at the cortical surface and around the vasculature. Each mesh of this structure was connected to each other, forming a complex labyrinth and being open toward the medullary area. Neither lymphoid cells nor any cells in any other organs were reacted with this Th-3 antibody. However, the reactivity of Th-3 with the thymic cortical stromal cells was observed not only in C57BL/6 mice which had been used as source of antigen, but also in other strains of mice such as C3H and BALB/C. Immunoelectron microscopy revealed that Th-3 monoclonal antibody was reactive with some component, diffusely present in the cytoplasm of cortical epithelial cells. The pattern of Th-3 positive meshwork in the thymic cortex was quite similar to that stained by either anti-IA or anti-IE antibody, but the Th-3 positive reaction was not inhibited by these anti-IA and anti-IE antibodies. Thymic nurse cells prepared by the method of Wekerle were positive for Th-3 antibody. On the contrary, Th-4 reacted only with epithelial cells in the thymic medulla. It was suggested that Th-3 monoclonal antibody detected some antigen specific to so called thymic nurse cells. PMID- 3101238 TI - The DRG dilemma. PMID- 3101239 TI - Subcutaneous implantation of the spleen as a new technique for experimental induction of hepatic Schistosoma mansoni egg granulomas. AB - Schistosoma mansoni egg granulomas were induced in the livers of mice by injecting eggs into spleens which had been surgically exposed with their vascular beds intact. Subsequent return of the spleens to a subcutaneous site allows repeated injections of eggs into the liver if necessary. PMID- 3101240 TI - Bacteriology of sickle cell leg ulcers. AB - The bacteria isolated on aerobic and anaerobic culture were compared in 80 unilateral ulcers in patients with homozygous sickle cell (SS) disease, 62 superficial skin lesions, and in 30 diabetic ulcers. In SS disease, the bacterial flora was predominantly aerobic and polymicrobial with Staphylococcus aureus, Pseudomonas aeruginosa and beta-haemolytic streptococci being the major isolates. Repeat sampling of 26 ulcers over a period of 23 weeks indicated the persistence of these three organisms, either singly or in combination in 21 ulcers. Although a variety of Enterobacteriaceae were recovered no single genus predominated and these organisms did not normally persist on follow-up. Simultaneous swabs from bilateral ulcers revealed similar if not identical flora in most cases, indicating good predictive value of a single swab in patients with multiple ulcers. Corynebacterium diphtheriae was recovered from eight ulcers and four of these strains were toxigenic. By contrast, the superficial skin lesions grew mainly S. aureus and beta 6-haemolytic streptococci, and the diabetic ulcers yielded a mixed growth of streptococci, Enterobacteriaceae and anaerobes. The recovery of known skin pathogens from most sickle cell leg ulcers, the persistence of these organisms, and the presence of associated lymphadenopathy, indicates that infection may be a significant factor in the pathology of these lesions. PMID- 3101241 TI - A simple and economical direct agglutination test for serodiagnosis and sero epidemiological studies of visceral leishmaniasis. AB - A simple and economical direct agglutination test for the detection of visceral leishmaniasis is described. Trypsin-treated, Coomassie Brilliant Blue-stained, formalin-preserved promastigotes were used as antigen in re-usable V-well microtitre plates. In 21 patients with recent kala-azar, titres of 1:51200 or higher were found. Cured kala-azar patients treated 4 to 14 months before testing, showed titres in the range of 1:3,200 to greater than 1:51,200. Healthy and diseased controls had titres below 1:1,600 with the exception of African trypanosomiasis patients who showed titres of 1:200 to 1:12,800, overlapping with the titres of cured kala-azar patients. Where trypanosomiasis is not a consideration, a titre of 1:1,600 could be considered indicative of visceral leishmaniasis, the sensitivity and specificity were then 100%. The test was applied to sera of 280 inhabitants of Baringo District, a known focus of visceral leishmaniasis in Kenya. When treated cases were included, the test showed a sensitivity of 100% and specificity of 99.3%. This test could be used in district hospitals and health centres in endemic areas as an aid in diagnosis of kala-azar and in the field for sero-epidemiological studies. PMID- 3101242 TI - Effect of iron prophylaxis on morbidity due to infectious disease: report on clinical studies in Papua New Guinea. AB - A controlled trial of iron prophylaxis (3 ml intramuscular iron dextran) to two month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria. The initial hypothesis was that iron deficiency increased susceptibility to infections and thus iron supplementation in a situation of actual or potential iron deficiency would diminish this susceptibility. Findings detailed elsewhere indicate that the placebo control group became relatively iron deficient and that the iron dextran group had adequate iron stores and a higher mean haemoglobin; however, prevalence of malaria recorded in the field was higher in the iron dextran group. Analysis of field and hospital infectious morbidity in the trial indicated a deleterious effect of iron dextran for all causes and for respiratory infections (the main single reason for admission). Total duration of stay in hospital was significantly increased in the iron dextran group. Analysis of other factors showed a deleterious effect of low weight for height at the start of the trial; a significant positive correlation between birth haemoglobin and hospital morbidity rates and a positive interaction between haemoglobin and iron dextran on hospital morbidity. A possible association between malarial experience and other infectious morbidity is discussed. PMID- 3101243 TI - Iron supplementation increases prevalence and effects of malaria: report on clinical studies in Papua New Guinea. AB - A placebo-controlled trial of intramuscular iron dextran prophylaxis for two month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria. The results indicate that the placebo group became relatively iron deficient whereas the iron dextran group had adequate iron stores and, in the absence of malaria, a higher mean haemoglobin. However in the iron dextran group there was a higher prevalence of malaria, as judged by parasite and spleen rates at 6- and 12-month follow-up; a lower haemoglobin associated with malaria when compared with the placebo group and a greater reticulocytosis in response to malaria infection. Within the placebo group it was noticed that the malaria rates were lower at follow-up in those infants who had had a low birth haemoglobin. In neither group was there apparent suppression of marrow activity in the presence of malaria. Malaria infection in both groups was associated with a significantly raised serum ferritin level and transferrin saturation. Over-all these data give evidence for a protective role of iron deficiency against malaria and would argue against the injudicious use of iron replacement in areas where malaria is endemic. PMID- 3101244 TI - Trypanosoma cruzi: constancy of clone pathogenicity for inbred mice during long term in vitro maintenance. AB - The reproducibility of infection of C3H/He mice with T. cruzi clones Sylvio-X10/4 and Sylvio-X10/7 maintained in the laboratory for 946 and 496 days respectively was assayed. Clone X10/7 from 15 different in vitro passages consistently induced an acute lethal infection (94.3% mortality) and constant survival time (Mean = 24.6 d.p.i.). Female mice survived significantly longer than males and mice older than 30 days at the time of infection survived significantly longer than younger mice. The mortality of mice infected with clone X10/4 from 23 different in vitro passages was lower (5.1%) and their survival longer (Mean = 42.7 d.p.i.) than mice infected with clone X10/7. High anti-T. cruzi IgG titres were detected in the plasma of all mice killed after 30 d.p.i. Histologically, the heart, skeletal muscles and/or large intestine contained intracellular parasites in 59% of the mice; parasites were found in mice of all groups tested. The hearts of all mice were comparably inflammed regardless of parasite passage number or duration of infection. These data demonstrate that the presentation and course of infection of inbred mice with two T. cruzi clones is not changed by either the duration or protocol used for in vitro maintenance; the reported loss or change in virulence of T. cruzi strains during long-term in vitro maintenance did not occur. Consequently, T. cruzi clones and inbred mice provide a dependable and reproducible means to study host-parasite interactions. PMID- 3101245 TI - Evaluation of routine anti-HBc screening of volunteer blood donors: a questionable surrogate test for non-A, non-B hepatitis. AB - Routine antibody to hepatitis B core antigen (anti-HBc) screening, recommended as a surrogate test to identify potential carriers of non-A, non-B hepatitis, was evaluated on 22,346 blood donors using currently available enzyme immunoassay (EIA) reagents. Of the 2 percent found reactive, the majority had cutoff-to sample absorbance ratios less than 2.0 and less than one-half had anti-HBc when tested by a radioimmunoassay (RIA) method. Only one of 2877 units donated previously by the reactive donors was implicated in a transfusion associated hepatitis case. These results raise questions about the use of currently available anti-HBc reagents as a surrogate test for non-A, non-B hepatitis. PMID- 3101246 TI - Hemolytic disease of the newborn caused by anti-Lan, anti-Jka, and anti-c. PMID- 3101247 TI - Positive antiglobulin tests due to intravenous immunoglobulin in patients who received bone marrow transplant. AB - To investigate an increased frequency of positive direct (DAT) and indirect (IAT) antiglobulin tests in bone marrow transplant (BMT) patients who received intravenous immunoglobulin (IVIG), serologic testing was performed weekly on blood samples from 94 consecutive BMT patients. Group 1 (47 patients) did not receive IVIG. Group II (47 patients) received high-dose IVIG as prophylaxis for cytomegalovirus infections. Before transplantation no alloantibodies were found in the serums of 92 patients and anti-E was found in the serums of two patients. DATs were negative in all patients before BMT. Four percent of Group I had a positive IAT and 13 percent had a positive DAT. In contrast, 25.5 percent of Group II patients had a positive IAT and 49 percent had a positive DAT, usually within 1 week after initiation of IVIG therapy (p less than 0.001). Antibodies identified in serums and eluates of patients in Group I were anti-A and anti-B. Antibodies identified in serums and eluates of patients in Group II were anti-A, B, -D, and -K. Twenty-one lots of IVIG were tested and antibodies identified were anti-A, -B, -D, and -K. The data suggest that the higher frequency of positive serologic tests in Group II was due to passively acquired antibodies from high dose IVIG. PMID- 3101249 TI - Evidence for a 'new' Rh gene complex producing the rare Cx (Rh9) antigen in the Somali population of East Africa. AB - Four unrelated propositi with an unusual Cx-positive Rh phenotype were found during a population survey of 513 Somalis. The Rh phenotypes of the propositi and their available relatives showed that the gene that produces the Cx antigen differs from that found in whites in that it is inherited with an Rh gene complex that produces no C or D. Instead, this gene complex produced es, c, and probably V, although it appeared that no f (ce) antigen was made. These findings suggest that Cx cannot be considered a simple variant form of C but rather a distinct rare Rh antigen that may occur in association with different Rh gene complexes. PMID- 3101250 TI - Identification of I-E alpha genes in H-2 recombinant mouse strains by F1 complementation. AB - Nine recombinant H-2 mouse strains with crossovers in the I region between I-E negative haplotypes f,q and I-E-positive haplotypes p,k were examined for I-E expression by microcytotoxicity dye exclusion assay. These recombinants were found to be negative for I-E expression. There are two possible genotypes in these recombinant mouse strains that could result in lack of I-E expression. Recombinants with crossovers between the E alpha gene and the S region would have both nonexpressed I-E alpha and beta genes (E beta fE alpha f, E beta qE alpha q) and recombinants with crossovers between the E beta and E alpha genes would have a nonexpressed E beta gene (E beta f or E alpha q) and a functional E alpha gene (E alpha k or E alpha p). To distinguish between these possible genotypes these recombinants were crossed to B10.A(4R), which carries a functional E alpha k gene but is I-E-negative due to a nonexpressed E alpha b gene. F1 mice were examined for transcomplementing I-E molecules by immunoprecipitation of 3H-leucine radiolabeled detergent lysates of spleen cells with a monoclonal I-E antibody (14 4-4). Detection of a transcomplementing I-E molecule was confirmed by immunoprecipitation with a monoclonal antibody (H9-14.8) specific for the I-Ek beta polypeptide chain derived from B10.A(4R) and by tryptic peptide map comparisons. Five recombinant mouse strains were able to complement with B10.A(4R) in F1 mice to generate a transcomplementing I-E molecule, and thus have an expressed I-E alpha gene (E alpha k or E alpha p). Four recombinants did not complement with B10.A(4R) in the F1 expression of I-E molecules, and thus have nonexpressed I-E alpha genes (E alpha f or E alpha q). PMID- 3101248 TI - Immunoreactivity of the Rho(D) antigen in cytoskeleton-free vesicles. AB - Skeleton-free microvesicles derived from D-positive red cells immunospecifically bind anti-D. Anti-D saturation binding yielded an equilibrium constant value (K = 1-2 X 10(8) I mole-1) similar to intact red cells. The vesicles contained band 3, the major sialoglycoproteins and, at high protein loads, low-molecular-weight polypeptides. Anti-D binding was referenced to total protein, phospholipid, and band 3 content to determine whether there was nonrandom segregation of the D antigen into vesicles. Selective segregation of the D antigen into vesicles could not be demonstrated unequivocally based on the methods and the assumptions of this study. The results, however, indicate that D reactivity does not require a membrane skeletal association. PMID- 3101251 TI - Severe protein energy malnutrition in Lesotho, death and survival in hospital, clinical findings. AB - In Lesotho's central hospital 55 (25%) of 218 admissions for severe PEM died during 1981 and 1982. Most deaths (62%) occurred in the first week. The most important causes of death were acute GE and pneumonia in marasmus and kwashiorkor, respectively. The cause of death remained obscure in 16 children, however. In marasmus a poor prognosis was significantly associated with the finding on admission of a temperature less than 36.5 degrees C (P less than 0.05), apathy (P less than 0.01) and a depigmented skin (P less than 0.05), while in marasmic kwashiorkor only the finding of the latter was significantly (P less than 0.05) associated with death. In non-survivors with kwashiorkor the following characteristics were observed significantly more often: complaints of diarrhoea and/or vomiting on admission (P less than 0.05), the finding of apathy, pallor, skin defects and hepatomegaly on admission (P less than 0.01), and the finding of a low serum albumen, Na+ and K+ in the first days (P less than 0.05). Irritability was significantly (P less than 0.05) more common in survivors with kwashiorkor. Xerophthalmia was observed only once. Infections were diagnosed in 86% of all and giardiasis in 28% of 146 children. Twenty-eight children contracted measles of whom 5 died. Severe PEM still carries a high mortality despite hospitalisation. The findings confirm the need for intensive management of severe PEM. PMID- 3101252 TI - Immunoprotective factors in breast milk and sera of mother-infant pairs. AB - We analysed breast milk and serum samples from 33 healthy Nigerian mother-infant pairs for concentrations of IgG, IgM, IgA, C3, C4 and lysozyme. We found that the mean IgG and IgM concentrations in maternal sera were three to four times higher than the levels in infant sera, and five to ten times higher than in breast milk. The IgA and lysozyme concentrations in breast milk were, however, slightly higher than the levels in infant sera, suggesting an active localized synthesis of these factors in the mammary gland. While 54.5% of the milk samples lacked measurable concentrations of IgM by radial immunodiffusion, IgA was consistently present in all the milk samples. The mean C3 concentration in maternal sera was 164 mg/100 ml, compared to 145 mg/100 ml and 11.5 mg/100 ml in infant sera and breast milk respectively. The C4 concentration was also considerably lower in breast milk than in maternal and infant sera. PMID- 3101253 TI - Usefulness of the TRH test in the management of patients with differentiated thyroid cancer. AB - Thirty patients thyroidectomized for differentiated thyroid cancer were studied. Serum TSH was assayed in basal conditions and after TRH stimulation, while patients were in suppressive therapy with thyroid hormones. The basal TSH was normal in all the patients and less than 2 microU/ml in 20 patients. The TRH test was negative (no TSH response) in 27 patients and in all the cases with the basal TSH lower than 2 microU/ml. PMID- 3101254 TI - [Effect of temperature on the kinetics of the phosphorylase reaction and phosphorylase activation induced by phosphorylase kinase in the skate Dasyatis pastinaca]. AB - The dependence of the phosphorylation reaction rate on the glucose-1-phosphate concentration is investigated in Dasyatis pastinaca in a wide temperature range (5-45 degrees C). In the temperature range of 20-40 degrees C nH is equal to 1.3 1.7. The disturbance of allosteric interactions of active sites with the loss of kinetic substrate cooperativity is observed at 45 degrees C. v(S)-Dependence with the intermediate plateau is obtained at 5 degrees C and high concentration of glycogen phosphorylase B (EC 2.4.1.1), that is explained by the formation of inactive tetramer. Studies in activation of glycogen phosphorylase B of Dasyatis pastinaca under the effect of glycogen phosphorylase (EC 2.7.1.38) kinase have revealed temperature-dependent changes in the pattern of kinetic curve. An assumption is advanced that the presence of the association-dissociation equilibrium in oligomeric forms of glycogen phosphorylase B with different enzymic activity and the effect of the temperature-dependent conformation state of this enzyme on the kinase reaction rate plays an essential role in regulation of glycogenolysis in the muscular tissue of ectothermal animals. PMID- 3101256 TI - [Rhesus prevention in Aalborg Hospital during the 1969-1979 decade]. PMID- 3101255 TI - [Effect of vitamins A and E on the structural-functional state of retinal lysosomes]. AB - Vitamins A and E (alpha-tocopheryl-acetate and retinol-palmitate) are studied for their effect on structural and functional state of retina lysosomes. These vitamins are shown to exert a pronounced membrane-tropic effect on lysosomes. Vitamin E in chosen concentrations stabilizes membranes of retina lysosomes both in the in vitro and in vivo experiments. Vitamin A acts on them as a labilizing agent. The mentioned effect of vitamins may be corrected by low-energy radiation of the monochromatic coherent light (lambda = 632.8 nm). It is substantiated experimentally that the stabilizing effect of vitamin E may be intensified in case of the action combined with laser radiation on lysosomes. The labilizing effect of vitamin A on membranes of organelles under study may be weakened by application of laser radiation of low intensities. PMID- 3101257 TI - [The Vamin 14 and 18 series. New concentrated parenteral solutions of amino acids]. PMID- 3101258 TI - [Ventilation in flats. Measurement of carbon dioxide and air exchange in retrofitted flats]. PMID- 3101259 TI - An effect of CO2 on the maximum safe direct decompression to 1 bar from oxygen nitrogen saturation. AB - An investigation into the maximum safe decompression step from oxygen nitrogen saturation to 1 bar was carried out with and without the presence of 0.02 bar carbon dioxide. The series, Islander 1, involved 13 teams of 5, fully informed, male volunteers carrying out simulated dives. One group of 6 teams carried out dives in an atmosphere of 0.4 bar oxygen, balance nitrogen (O2-N2); another group of 7 teams used an atmosphere of 0.38 bar oxygen, 0.02 bar carbon dioxide, balance nitrogen (O2-N2-CO2). The dives consisted of a 48-h stay at 1.7 or 1.8 bar to saturate the tissues, followed by decompression to 1 bar air at 0.5 bar/min. Two decompression parameters were studied; the incidence of decompression sickness (DCS) in the 24 h postdecompression, and the incidence and grade of venous gas emboli (VGE) in the first 6 h postdecompression. The grade of VGE was assessed using the Kisman-Masurel scoring system which produces a bubble grade with the subject at rest and after movement. No significant difference was found in the incidence of DCS between the two groups. Twenty subjects were decompressed from 1.7 bar using each mixture, without signs or symptoms of DCS. However, after decompression from 1.8 bar there were 2 cases of DCS in 10 subjects in the O2-N2 group and 2 cases in 15 subjects in the O2-N2-CO2 group. The incidence of detectable VGE was always lower in the O2-N2-CO2 group at both saturation pressures; at 1.7 bar the VGE incidence was lower by 40% (P less than 0.05) at rest and by 55% (P less than 0.001) after movement. At 1.8 bar the reduction was 3% (NS) at rest and 30% (NS) after movement. The results indicate that decompression from 1.8 bar to 1 bar, with or without the presence of 0.02 bar carbon dioxide, is likely to produce more than 5% DCS. PMID- 3101260 TI - Metabolism-related tissue-binding of halogenated hydrocarbons. PMID- 3101261 TI - A permanent subcutaneous catheter for drawing blood samples and for intravenous fluid therapy in a diabetic woman with recurrent ketoacidosis. PMID- 3101262 TI - Renal cyst puncture studies. AB - The edict to contain costs and meet goals imposed by DRG remuneration policies mandates the work-up of asymptomatic renal mass lesions on an outpatient basis. This proved feasible in 98 per cent of patients. The vast majority of such mass lesions (82 to 90 per cent) is diagnosed with acceptable confidence by computed tomography and sonography alone. For a shrinking group of such patients, yet still 16 to 18 per cent, guided percutaneous aspiration biopsy is necessary to affirm the diagnosis. However, this technique has been refined during recent years to incorporate the use of thin needle equipment and can now be performed on an outpatient basis without significant risk of morbidity. For diagnosing hyperdense inflammatory and infected renal cysts, guided percutaneous aspiration is recommended as the most effective method. This procedure should take precedence over surgical exploration because it can diagnose and provide pertinent bacteriologic information that may determine the course of therapy. In many instances inflammatory cysts or even silent renal abscesses are diagnosed by a percutaneous aspiration technique that is then expanded to serve therapeutic purposes such as percutaneous drainage. Even these procedures can be performed safely on an outpatient basis provided the patient is followed closely. Because complications of percutaneous aspiration procedures are extremely rare, the procedure can be used safely on an outpatient basis. The impact of magnetic resonance imaging on the diagnosis of asymptomatic space-occupying lesions of the kidney is as yet not fully determined; however, this method appears promising for diagnosing some of the refractory lesions such as hemorrhagic cysts, aneurysms, or arteriovenous malformations. PMID- 3101263 TI - [Diagnosis of reflux in children with CO2 and ultrasound. Technic and preliminary results]. AB - So far diagnosis and follow-up of vesico-uretero-renal reflux (VUR) is primarily based on radiological voiding studies. However this is accompanied by significant gonadal radiation doses. The goal of this study was to compare the diagnostic accuracy of real time sonography, following CO2 instillation into the bladder with that of conventional radiography in the diagnosis of VUR in children. By means of sonography 13 out of the 16 grade III, and all 16 grade IV and V VUR were seen. 4 out of 7 grade II VUR could be demonstrated. No grade I reflux has been diagnosed. In conclusion, sonography reflux study is a sensitive and specific screening and follow up procedure for VUR. At present 75 per cent of all VUR's can be diagnosed by sonography alone. PMID- 3101264 TI - Urethral diverticula in females. Alternative surgical treatment. AB - A technique is described which may be utilized to advantage in the treatment of large urethral diverticula. The hazards of extensive subtrigonal dissection are alleviated by leaving a portion of the diverticular floor intact and marsupializing it to the vaginal mucosa. PMID- 3101265 TI - [Substantiation of the use of the helium-neon laser (data of a bacteriologic study)]. PMID- 3101266 TI - [Levels of thyroxine, beta carotene and vitamin A during successful and unsuccessful insemination of heifers]. AB - We studied the concentrations of thyroxine (T4), beta-carotene and vitamin A (vit. A) on the day (zero-th day) of the first successful and unsuccessful insemination of 63 heifers that were administered feed rations balanced according to the Czechoslovak standard CSN 46,7070, housed all the year round, inseminated at uniform time (8:00-9:00 a. m.) and with blood samplings at uniform time (10:00 12:00 a. m.). In the repeat-breeder heifers during the first insemination the above parameters were determined in the same conditions on the day of their second, or third successful and also unsuccessful insemination; the changes relevant to the first insemination were evaluated. In relation to the day of the first successful insemination, we recorded a significant increase in T4 concentration (P less than 0.001; P less than 0.001) on the day of the second, or third successful inseminations. During the second insemination we recorded significantly lower T4 concentrations in the cows which had failed to be inseminated in comparison with successfully inseminated cows; these concentrations did not differ significantly from T4 concentrations in the heifers that failed to become pregnant in the first insemination. Parallelly with the rise in T4 concentration, beta-carotene concentrations also increased during the second and third inseminations (P greater than 0.05). No difference was recorded in beta-carotene concentrations after the first and second unsuccessful inseminations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101267 TI - [Acid-base equilibrium in the blood in cattle in relation to the incidence of DFD (dark, firm, dry) meat]. AB - We studied changes in the parameters of the acid-base balance of the blood in cattle before animal transport to the slaughterhouses, after transport, after stunning and before bleeding. At the same time we studied the occurrence of DFD meat by measuring the pH value of the muscle and by determining the meat color. We found out that the disorder of acid-base balance was less manifest, with respect to the large capacity of the buffer systems of the blood, than the changes caused by glycogenolysis in the muscle. PMID- 3101268 TI - [Coccidiosis in suckling calves raised on large farms]. AB - In a large herd of pigs whose piglets suffered from diarrheas coprological examination revealed the great incidence of Isospora suis coccidia in piglets. The first oocysts were found out in seven-day piglets; the highest incidence was observed in twelve-day piglets (65.9%); the time of oocyst elimination (patency) was five to six days. The oocysts appeared in the excrements of piglets two to three days after the diarrhea onset. Individual examinations of piglets demonstrated the correlation between the intensity of clinical signs and the numbers of eliminated oocysts. No oocysts of I. suis were found either in sow excrements or gilt excrements. The I. suis oocysts were diagnosed in the excrements of piglets from first-farrowing sows and in the excrements of piglets from the sows, in the litters of which I. suis had already been demonstrated. Evaluating the therapeutic and preventive effects of the anticoccidic drug amprolium no significant difference was recorded in the I. suis incidence between the medicated group and the control group. PMID- 3101269 TI - [Trends in the quantity of foreign substances in feed mixtures and in pigsty dust at large pig farms]. AB - In the period from January 1983 to December 1985 we examined thirty-five samples of commercial feed mixtures for pigs and thirty samples of pigsty dust deposition from large pig-houses in a region with extensive mining (lignite extraction) situated in the Hodonin district. In comparison with the contents of contaminants in the feed mixtures over the period from January 1983 (1/83) to June 1984 (6/84), the zinc and lindane concentrations increased to 213.3% (P less than 0.01) and 133.3%, respectively, from July 1984 (7/84) to December 1985 (12/85). The concentrations of copper, manganese, lead, cadmium, mercury (P less than 0.05), DDT (P less than 0.01) and aflatoxin B1 in the feed mixtures decreased. The highest permissible amount of contaminants in the feed mixtures was exceeded in the 1/83-6/84 period in cadmium (limit value 0.3 mg per kg) and mercury (limit value 0.1 mg per kg), in the 7/84-12/85 period only in zinc (limit value 250 mg per kg). In comparison with the values of contaminants in pigsty dust deposition recorded from January 1983 to June 1984, the lead concentration increased to 555.5% in the 7/84-12/85 period, lindane concentration rose to 569.0% (P less than 0.01), zinc concentration to 220.5% (P less than 0.01), the copper, manganese, cadmium, mercury concentrations (P less than 0.05) decreased, and the concentrations of DDT, aflatoxin B1 and polychlorinated biphenyls also dropped. It is desirable to evaluate in regular intervals the spectrum of contaminants both in feed mixtures and in pigsty dust deposition and to monitor other potential sources of contaminants in the pig-houses. PMID- 3101270 TI - [Experimental control of the process of lead absorption and deposition in domestic ducks]. AB - A trial was conducted with 40 domestic ducks of the White Pekin breed at the age of 40 days: thirty pieces of lead shot were introduced as a single dose in the gizzard. The process of lead resorption and deposition was found not to be significantly influenced by the therapeutic treatments nor changes in the composition of feed. A week after the administration of shot a significant increase was recorded in the content of lead to 4.32 mg in liver, to 11.36 mg in kidney and to 1.15 mg in muscle (the respective values for the control animals were 0.07, 0.11 and 0.06 mg per kg). At the end of the trial after three weeks of treatment and administration of experimental diets, no significant differences were recorded in lead content in liver, kidney and muscle between the untreated and treated ducks nor ducks fed experimental diets. PMID- 3101271 TI - Experimental microcyst sarcocystis infection in lambs: pathology. AB - Six 34- to 42-day-old lambs raised in coccidia-free conditions were inoculated with 70,000 sporocysts derived from sheep heart with microscopic sarcocysts. Fever and mild anorexia occurred between 25 and 33 days after inoculation. A transient anaemia was most marked 32 days after inoculation. Lambs were killed and examined 14, 25, 33, 42, 60 and 81 days after inoculation. Gross lesions were absent. First and second generation meronts were present in endothelial cells at 25 and 33 days after inoculation. Meronts were most numerous in kidney glomeruli. Developing sarcocysts were rare at 42 days after inoculation. Sarcocysts with a primary cyst wall 2 to 3 micron thick composed of palisade projections were common at 60 and 81 days after inoculation in striated muscle and brain. Mild to severe striated muscle myositis and non-suppurative encephalitis or encephalomyelitis with glial nodules were observed 25 to 81 days after inoculation. Sarcocyst frequency varied considerably; it was highest in myocardium, M vastus intermedius, M vastus medialis, M extensor carpi radialis and tongue muscle and was lowest in M masseter. PMID- 3101272 TI - Parasitic laryngeal papillomatosis in a horse. AB - Papillomatous lesions intruding into the laryngeal airway were identified in an imported polo pony during a routine neurological examination for partial quadriplegia. Histological examination established a diagnosis of laryngeal besnoitiosis but it is unlikely that the laryngeal parasitism was associated with the cerebellar neuropathy which was also present. PMID- 3101273 TI - Demonstration of a candidate virus for turkey rhinotracheitis in experimentally inoculated turkeys. PMID- 3101274 TI - Effects of luteinising hormone on embryo production in superovulated cows. AB - Equivalent doses of follicle stimulating hormone (FSH) produced the same number of embryos and ova from a single flush irrespective of the luteinising hormone (LH) content of the superovulating drug (P less than 0.108). As the LH content of the FSH increased, the proportion of transferable embryos decreased (P less than 0.001) because the proportion fertilised decreased (P less than 0.001) and the degeneration rate of the fertilised embryos increased (P less than 0.002). FSH-W free from detectable luteinising hormone produced 8.8 embryos per flush of which 5.7 were transferable, representing 7.6 fertilised embryos of which 21 per cent had degenerated. The addition of a very small quantity of LH (FSH/LH ratio more than 500) resulted in 5.8 transferable embryos from a total of 10.6, of which 9.0 had been fertilised and 34 per cent of those fertilised had degenerated. Commercial FSH-P (FSH/LH less than 100) produced 3.3 transferable embryos from a total of 8.1, of which six had been fertilised and 39 per cent of those fertilised had degenerated. The luteinising hormone content of FSH-P has to be controlled and limited for optimum superovulation in cattle. PMID- 3101275 TI - Pseudomonas aeruginosa mastitis in a Sabi ewe. PMID- 3101276 TI - Isolations of Cache Valley virus in Texas, 1981. AB - Two strains of the same virus (isolates AR 168 and 7856), were isolated in 1981 from an apparently healthy cow and a sick sheep in TX, U.S.A. These isolates were shown to be members of the Bunyamwera serogroup (family Bunyaviridae, genus Bunyavirus) by complement-fixation tests. Serum dilution-plaque reduction neutralization test results indicated that the isolates are closely related to Cache Valley virus. The virus isolates were characterized by sensitivity to lipid solvent, size (50-100 nm by filtration and 70 nm by electron microscopy), heat (56 degrees C) and pH 3 lability, cytopathic effects or plaques in cultures of Vero, LLC-MK2, embryonic bovine testicle and PS cells, and pathogenicity for suckling and weaned mice by the intracranial but not the intraperitoneal route. Gnotobiotic and conventional sheep and goats were experimentally infected by inoculation with one of the isolates given either intravenously or intraperitoneally. Elevation of body temperature, depression, tremors, muscle spasms, disorientation, feeding anomalies, convulsions, or other signs of central nervous system disturbances were observed. PMID- 3101277 TI - [Sensitivity of Ps. aeruginosa to disinfectant agents]. AB - Pseudomonas aeruginosa strains, isolated from semen of bulls as well as from the surrounding milieu at Artificial Insemination Stations, were tested for susceptibility to disinfection agents, such as fesiasept, concentrate C4, and chloramine with 25% active chlorine and sodium hydroxide. The investigation was carried out in vitro under practical conditions too. The analysis of results led to the conclusion that in the case of environmental contamination with Ps. aeruginosa along with semen contamination most effective proved concentrate C4 in the form of 2.5 per cent water solution. The disinfection of lab glassware and equipment, instruments, towels, kerchiefs, cloths, and white overalls and aprons is to be carried out with 1.5 per cent water solution of chloramine. PMID- 3101278 TI - [Carbohydrate metabolic indices of ketotic and healthy cows]. AB - Some of the indices of carbohydrate metabolism were studied in 30 freshly calved, high-producing cows affected with the disease and after they had recovered from ketosis as well as in 25 control cows. Investigated were the volatile fatty acids (VFA), ketone bodies, pH, and the count and composition of infusoria in the rumen content; the sugar, ketone bodies, and VFA in the blood--all being considered the most characteristic indices of carbohydrate metabolism in ruminants. With diseased cows pH in the rumen was 22 per cent lower than in the controls; the total count of infusoria per cu.cm was more than twice lower than the values found after recovery and those in the controls. Diplodinium and Isotricha infusoria were twice as low as the values found in the controls and after recovery. Entodinium infusoria were totally lacking in the rumen content of the affected animals, while the ketone bodies were 13.5 to 15.5 times as high, and VFA were 37 to 49 per cent lower. The level of the individual VFA fractions was altered; it was 2.4 to 2.8 times lower for acetic acid and 1.8 to 1.9 lower for propionic acid, while it was 1.8 to 2.1 times higher for butyric acid. The blood level of sugar in the diseased cows was more than twice lower, while the blood level of ketone bodies was 12 to 13 times higher; it was also higher (8 to 13 times) for VFA as compared with the values shown by normal cows and cows that had recovered from ketosis. PMID- 3101279 TI - The application of various electron microscopic techniques for ultrastructural characterization of the human papillary heart muscle cell in biopsy material. AB - Various electron microscopical techniques have been applied to biopsy material obtained from patients suffering from mitral stenosis in order to characterize the subcellular organization of the hypertrophied papillary muscle. Small pieces of the same sample were processed for correlative transmission - (TEM) and scanning - (SEM) electron microscopical studies. TEM was carried out on conventionally fixed tissue with or without en bloc staining with a Cu-Pb citrate solution, and on freeze fracture replicas, while cryofractured material was studied by SEM. Stereo electron micrographs of the Cu-Pb impregnated tissue and of the cryofractured material were especially useful for studying the spatial distribution and relationship between various cell organelles. The myofilaments of the hypertrophied cells were arranged in a normal hexagonal pattern. Regions with irregular orientation of the myofibrils were occasionally seen. Accumulations of interfilamentous glycogen particles adjacent to the Z-bands were characteristic patterns of the contracted muscle cells. The extensive nexuses frequently observed in the subsarcolemmal regions may reflect functional alterations of the intercommunication between hypertrophied cells. The T-tubules were relatively few and irregularly distributed, and the complexity of the sarcotubular system (SR) revealed regional variations. Excellent visualization of the interior couplings between the SR and the T-tubules was achieved by studying thick sections of Cu-Pb impregnated tissue in the TEM. The dense staining of the various intracellular membranes when compared with the almost unstained external membranes including the free cell surface, intercalated disc and T-system, strongly indicates differences in chemical and functional properties of the two membrane systems. En bloc staining resulted also in contrasted glycogen as well as components of the nucleolus and the heterochromatin. The biochemical basis for the selective staining remains obscure; it may be a result of binding of heavy metal ions to carboxyl groups of specific proteins, and/or it may represent deposits of lead phosphate. PMID- 3101280 TI - Epithelioid sarcoma and epithelioid hemangioendothelioma: an immunocytochemical and lectin-histochemical comparison. AB - Epithelioid sarcoma (ES) and epithelioid hemangioendothelioma (EH) both occur preferentially in the soft tissues, and may be confused with one another microscopically. We compared 8 examples of each tumor immunohistochemically, using formalin-fixed tissue, the ABC method, unconjugated Ulex europaeus I agglutinin (UEA), rabbit antibody to UEA, and monoclonal antibodies to epithelial membrane antigen (EMA), cytokeratin (CK), factor VIII-related antigen (FVIIIRAG), and blood group isoantigens A, B, and H (BGI). Six of 8 cases of ES, and 7 of 8 epithelioid hemangioendotheliomas bound UEA; similarly, 6 of 8 ES cases were reactive for BGI, as were 4 of 8 examples of EH. All epithelioid sarcomas were positive for CK, and 7 displayed EMA, whereas these antigens were lacking in EH. Conversely, 5 of 8 cases of EH contained FVIIIRAG, which was absent in all examples of ES. These findings underscore the nonspecificity of UEA-binding and BGI-expression as markers of endothelial differentiation. Moreover, they suggest that sole reliance upon these immunohistologic reactants for the identification of vascular tumors may result in diagnostic error. Inasmuch as ES and EH differ in biological behavior, such a mistake would be significant. Thus, we advocate the inclusion of immunostains for EMA, CK, and FVIIIRAG in the evaluation of histologically-similar cases of epithelioid sarcoma and epithelioid hemangioendothelioma. PMID- 3101281 TI - Endothelial cilia in human aortic atherosclerotic lesions. AB - "Primary" cilia were present in the endothelial cells of human aortic fatty dots and streaks but not in those of normal intima. They had the features of cilia of the "9 + 0" axonemal configuration observed in many other cells. A lateral foot process and transitional fibers "anchored" the ciliary basal body in the cytoplasm, but rootlets were not identified in material examine. Ladder-like configurations interconnected the two centrioles (= diplosome) of control endothelium. The "primary" cilia of endothelium differed from those of the rudimentary type observed in smooth muscle cells in similar lesions of man, but shared many features with cilia of those present in experimental atherosclerosis in rabbit. Cilia were rarely described in vascular endothelium. It is believed that, to date, they were not reported to occur in normal or pathological arteries in man. It is being stressed that whereas the significance of these unusual organelles remains uncertain, their widespread occurrence may indicate that their role is more important than was believed previously, and they should cease being a curiosity only. PMID- 3101282 TI - Granulomatous pancreatitis--granulomas in chronic pancreatitis. AB - Granulomatous pancreatitis can be described only in infectious granulomas and pancreatic involvement by systemic granulomatosis. The presence of classical chronic tryptic pancreatitis in addition to individual sarcoidosis granulomas in one of our cases of sarcoidosis, shows that pancreatitis in a patient with generalized granulomatosis should not necessarily be considered granulomatous pancreatitis. A variety of foreign-body granulomas found in the pancreas may be explained by previous surgical operations, and other foreign bodies introducted iatrogenically. Occasionally, the pancreas in chronic pancreatitis contains granulomas that must be considered foreign body granulomas, although the causal foreign body cannot be identified. We believe that we can identify inspissated secretion that has passed out of the ductal system into the interstitium as the foreign body responsible. It is not possible to establish whether such iatrogenic measures as manipulations of the duct with back-up of the secretion within the ductal system, has any causative involvement in this secretion oedema. However, the absorption of the individual parenchymal secretions is impaired to such a degree that any extravasated remain "in situ" for a lengthy period. The absorption of the aqueous constituents leads to inspissation, so that it can finally be absorbed only through the formation of foreign body granulomas. The same granulogenic property in highly scarred pancreatic parenchyma is also recognizable in the abnormal degradation mode of normally absorbable Ethibloc, and in the excessive arterial and periarterial reactions following angiography. The presence of granulomas within the parenchyma of the pancreas in chronic pancreatitis, many of which have been induced by endogenous and/or exogenous foreign bodies would not lead us to refer to a granulomatous pancreatitis, since the remaining sections of the parenchyma manifest typical necroses and scar foci of chronic pancreatitis. We would characterize these granulomas by the term "granulomas in chronic pancreatitis", and differentiate this from granulomatous pancreatitis. PMID- 3101283 TI - Olivo-ponto-cerebellar atrophy with muscular atrophy, joint contractures and pulmonary hypoplasia of prenatal onset. AB - The clinical and pathological features of a female neonate with congenital joint contractures and pulmonary hypoplasia are described. Neuropathological examination revealed a widespread neuronal degeneration with a predominantly olivo-ponto-cerebellar distribution and muscle pathology consistent with neurogenic atrophy. This is the first reported case of congenital joint contractures and pulmonary hypoplasia with pathologically documented olivo-ponto cerebellar degeneration. The observation further illustrates that the so-called fetal akinesia sequence or Pena-Shokeir I syndrome is an aetiologically non specific symptom complex that can be caused by a number of underlying mechanisms. PMID- 3101285 TI - [Advantages of rotational radiotherapy in deep and centrally located tumors]. PMID- 3101284 TI - Immunohistological analysis of the lymphoid infiltrate in cutaneous malignant melanomas. AB - The immunological phenotypes of the lymphoid cells in 39 cutaneous malignant melanomas have been investigated by staining cryostat sections with a panel of 20 monoclonal antibodies against lymphoid cells and their subsets. Staining was performed by the alkaline phosphatase: anti-alkaline phosphatase (APAAP) method in which the substrate label (red) is easily distinguishable from melanin. The lymphoid infiltrates had an essentially identical composition in all cases, consisting of T-lymphocytes associated with both Langerhans cells and HLA-DR positive tissue macrophages. B-lymphocytes and natural killer cells were either absent or only present in low numbers. The ratio between T8 (suppressor/cytotoxic) and T4 (helper/inducer) lymphocytes varied and showed no correlation with melanoma subtype, level of invasion or magnitude of lymphocytic response. Examination for markers associated with T-cell activation and/or with cell proliferation revealed that all lesions contained HLA-DR-positive T lymphocytes, whereas expression of the transferrin receptor and the interleukin-2 receptor (Tac-antigen) occurred mainly in melanomas with a significant inflammatory infiltrate. These data support the concept that malignant melanomas are capable of evoking autologous T-cell immune reactions. PMID- 3101286 TI - Influence of the primary anticoagulant on the recovery of factor VIII in cryoprecipitate. AB - The influence of anticoagulant on overall factor VIII-yield was measured by drawing blood from one donor simultaneously in three bags containing ACD, CPD and heparin, respectively. After parallel processing factor VIII:C and factor VIII:CAg were measured. It is concluded that, under the circumstances used in this experiment, CPD gives the highest yield of factor VIII. PMID- 3101287 TI - A human-human monoclonal anti-D by direct fusion with a lymphoblastoid line. AB - The human lymphoblastoid cell line W1-L2-729-HF2 has been fused with B cells from a plasmaphoresed anti-D donor immunized with D+ cells. A stable monoclonal antibody-producing cell line has been produced which yields culture supernatant of good titre without the need for concentration. The production and use of this reagent as an alternative Rh D typing reagent for use by saline and enzyme manual tests and automated tests in a Technicon 16C machine is discussed. Du red cells are detected in enzyme enhanced tests. PMID- 3101288 TI - Rh(D) alloimmunization in the absence of exposure to Rh(D) antigen. AB - An anti-D was detected in the serum of an Rh(D)-negative primigravida. There is no history of previous pregnancies or blood transfusions. The husband and infant are both Rh(D)-negative. PMID- 3101289 TI - Post-transfusion non-A, non-B hepatitis after cardiac surgery. Prospective analysis of donor blood anti-HBc antibody as a predictive indicator of the occurrence of non-A, non-B hepatitis in recipients. AB - We prospectively studied the incidence of post-transfusion non-A, non-B hepatitis in 64 cardiac surgery patients: 4 (6.25%) developed non-A, non-B hepatitis after an incubation period of 4-10 weeks. Units of blood products from donors seropositive for antibody to hepatitis B core antigen (anti-HBc) were not associated with a greater risk of non-A, non-B hepatitis in recipients than units from seronegative donors. Our data indicate that donor blood anti-HBc testing is of no value as a screening method to reduce the incidence of post-transfusion non A, non-B hepatitis. PMID- 3101290 TI - The impact of the economic crisis on health and health care in Latin America and the Caribbean. PMID- 3101291 TI - [Pulmonary hypertension from the viewpoint of the pediatric pulmonologist]. AB - The main cause of secondary pulmonary hypertension in the view of a pulmonologist is alveolar hypoventilation - eventually potentiated by acidosis and hypercapnia which leads to reflectory hypoxemic vasoconstriction of the small pulmonary arteries. Anatomic changes in the pulmonary vessels may be absent or may be limited to medial hypertrophy of the arterioles. If the underlying cause of the hypoxia can be corrected, this reflectory pulmonary hypertension is reversible. In diffuse progressive lung disease, interstitial fibrosis with destruction of the alveolar wall and capillaries may occur, leading to restriction of the pulmonary vascular bed. In such cases pulmonary hypertension may not be completely reversible. The most frequent causes of pulmonary hypertension in childhood are obstructive (e.g. Cystic Fibrosis) or restrictive lung diseases (e.g. interstitial fibrosis). Rare but important in the differential diagnosis are upper airway obstruction, thoracic cage deformity, neuromuscular disorders, high altitude and respiratory center dysfunction. The therapy is elimination of the underlying disease or optimal treatment. In addition prophylactic or therapeutic longterm application of oxygen is more efficient than treatment with pulmonary vasodilators or modern substances like Almitrine. Right heart decompensation should be treated by diuretics. The longterm prognosis is dependent of the underlying disease and is poor in a chronic progressive lung disease like cystic fibrosis and certain types of lung fibrosis. PMID- 3101292 TI - [Hemodynamic studies of nifedipine (Adalat) in pulmonary hypertension in childhood]. AB - Under long-term oral treatment with nifedipine (N) 2 of 3 patients (2 children with VSD and Eisenmenger, 1 patient with Truncus I after corrective surgery) showed a remarkable improvement in exercise tolerance and reduction in the total pulmonary resistance. Therefore a single-dose testing with N was performed in 9 patients aged 2 to 20 years with primary pulmonary hypertension (n = 2), secondary pulmonary hypertension because of congenital heart disease with intracardiac shunts (n = 6) and after correction of Truncus Type I (n = 1). Before and after the injection of 0.5 mcg/kg of N into the main pulmonary artery, pulmonary artery pressure, cardiac output and systolic blood pressure were measured at 1 minute intervals during right heart catheterization. The maximal reaction occurred 3 to 4 minutes after the injection. The total pulmonary vascular resistance decreased significantly from 2684.2 +/- 1829.2 to 1300.2 +/- 1117.0 dyn.sec.cm-5.m2 (p less than 0.025), the cardiac index increased significantly from 3.1 +/- 1.65 to 5.73 +/- 1.95 l/min.m2 (p less than 0.01) concomitantly with a mild reduction in the mean pulmonary artery pressure. No significant change in heart rate and systolic blood pressure was seen; no side effects were observed. 4 of the 5 patients with the highest pulmonary vascular resistance showed the best positive reactions. Therefore these 9 patients may benefit from a long-term oral treatment with nifedipine. PMID- 3101293 TI - Duodenal carcinoid in neurofibromatosis: a calcitonin- and amyloid-containing tumor. PMID- 3101294 TI - [Cerebral seizures in the course of pediatric encephalitis]. PMID- 3101295 TI - [Viral hepatitis as a nosocomial infection at the dialysis center--a current 5 year study]. PMID- 3101296 TI - [Characterization of Pseudomonas aeruginosa isolates from intensive care units by sero-, lyso- and pyocin typing]. PMID- 3101297 TI - Duodenal varices. Report of 13 cases. AB - Only a few cases of Duodenal Varices (DV) have been reported in the world literature mostly by radiological studies, at operations, or autopsies. Alberti described DV for the first time in 1931. The visualisation of DV by fiberoptic endoscope was first made in 1973 by Kunisaki et al. (one case) and later by Kunert and Ottenjann in 1976 (one case). In this study we present 13 cases of DV diagnosed in the period from June 1979 to May 1983 out of 5664 endoscopic examinations performed in the Endoscopy Unit of Riyadh Central Hospital and giving a prevalence of 1:435. 598 cases of Oesophageal Varices (OV) were found in these series, so that the relation DV:OV is 1:46 in this study. The etiology of DV is mostly liver fibrosis due to schistosomiasis (9 cases). In the rest of the cases we found av-malformation (one case), cancer of the head of pancreas (one case) and Hodgkin's disease with enlarged lymph-nodes and ascites in association with chronic duodenal ulcer (one case). In one case the etiology remained unknown. 4 patients had no oesophageal involvement (isolated DV). The cases will be discussed in detail. PMID- 3101298 TI - [When is it possible to discontinue therapy in pemphigus vulgaris?]. AB - Discontinuation of therapy in pemphigus vulgaris is risky, even after long remission under therapy. In active pemphigus vulgaris, levamisole suppresses the formation of T-cell-rosettes. The change from suppression to stimulation under the influence of levamisole, parallel to the disappearance of pemphigus antibodies seems to indicate that the therapy may be discontinued with all due caution. PMID- 3101300 TI - [Mycotic intracranial aneurysm in infective endocarditis of the mitral valve]. AB - A 20-year-old woman suffering from mitral valve endocarditis due to streptococcus faecalis infection after blunt trauma and splenectomy complained of severe headache 18 days later. Cerebral angiography showed a left posterior artery aneurysm. A craniotomy was performed and the aneurysm could be successfully removed. The postoperative neurological status showed a mild transient right hemiparesis. The patient underwent mitral valve replacement with a St. Jude Medical prosthesis 14 days after brain surgery. The patient was in stable neurologic and hemodynamic conditions at the time of discharge 3 weeks after valve replacement. PMID- 3101299 TI - [Hemodynamic effects of nitroglycerin following acute inhibition of prostaglandin synthesis]. AB - The mechanism of action by which nitrates produce vasodilation has not been fully clarified so far. Experimental studies indicate a possible relationship to the prostaglandin system. This study describes the consequences of acute prostaglandin synthesis inhibition on the hemodynamic effects of nitroglycerin in patients with stable angina pectoris. Intravenous application of 1 g acetylsalicylic acid was associated with a small but significant blunting of the pressure decline in the pulmonary and systemic circulation following the sublingual administration of 0.8 mg nitroglycerin. Premedication with 75 mg indomethacin i.m. was followed by a decrease in pressure decline in the pulmonary artery during intravenous nitroglycerin infusion. Significant inhibition of prostaglandin synthesis was shown by a substantial decline in plasma levels of circulating prostaglandin metabolites in both experiments. These results indicate that the mechanism of action of nitroglycerin may be partially mediated by vasodilatory prostaglandins. PMID- 3101301 TI - [A variant method for immunoturbidimetric determination of apolipoproteins A-I and B in the serum]. PMID- 3101302 TI - A new archaic Homo sapiens cranium from Eliye Springs, West Turkana, Kenya. PMID- 3101303 TI - Postcanine tooth size and diet in anthropoid primates. PMID- 3101304 TI - [Theory of thermally-motivated form adaptation in land mammals, especially humans]. PMID- 3101305 TI - [Immunogenetics in the human]. PMID- 3101306 TI - [Parenteral and tube feeding]. PMID- 3101307 TI - [Diseases of the bile ducts and pancreas]. PMID- 3101308 TI - The optimum form of dietary nitrogen in gastrointestinal disease: proteins, peptides or amino acids? PMID- 3101309 TI - [Protein and amino acid metabolism in liver failure--therapeutic infusion and dietary sequelae]. PMID- 3101310 TI - [Methodological approaches to the study of parenteral and tube feeding in an experiment]. PMID- 3101311 TI - [Feeding of patients with maxillo-facial disorders]. PMID- 3101312 TI - [beta Phenylethylamine: psychopharmacological and clinical aspects]. AB - beta Phenylethylamine (PEA) is an endogenous amine that resembles amphetamine in chemical structure and has been identified in human and other mammalian brains and in many peripheral tissues. Although PEA exists in much smaller amounts than monoamines, the mode of action of PEA as a neuromodulator is of special interest. In this paper the author reviews animal and clinical studies on PEA. The first section deals the methods for the determination of PEA in mammalian brains and human urine. PEA is reliably measured using spectrofluorometric, gas chromatographic-mass spectrometric methods. The second chapter reviews the changes in animal behavior elicited by PEA. The administration of PEA induces stereotypy and increased motor activity in animals. The third part reviews the effect of PEA on dopamine, noradrenaline, serotonin and tyramine metabolism in mammalian brains. The fourth chapter examines recent clinical evidence suggesting a role for PEA in schizophrenia and affective disorders. PMID- 3101313 TI - [Effect of thyrotropin-releasing hormone (TRH) and its analog DN-1417 on scopolamine-induced impairment of short-term memory in rats]. AB - The effects of a few drugs, which are known to activate central nervous system, on scopolamine-induced impairment of short-term memory (STM) were studied in a delayed alternation task in rats. Rats were initially trained using a delayed alternation task in which a forced run to one arm of a T-maze was followed by a free-choice run. A correct free-choice response was defined as a turn toward the arm opposite to that in the forced run, and was rewarded with food pellets. After repeated training of the 60 sec-delayed alternation task, the treatment with scopolamine (0.2 mg/kg, ip) at 20 min before the test resulted in a significant decrement in the correct response. The scopolamine-induced impairment of STM was significantly antagonized by DN-1417 (10 mg/kg, ip) given 1 hr before the test. However, TRH (3-30 mg/kg, ip) and methamphetamine (0.2-1.0 mg/kg, ip) did not improve the scopolamine-induced impairment in the task. In rats without treatment with scopolamine, these drugs did not affect the percent correct response. These results suggest that DN-1417 may have an improving effect on the impairment of STM induced by a decreased cholinergic activity. PMID- 3101314 TI - Selective medium for isolation of saprophytic coryneform bacteria. AB - Out of 64 test chemicals for which the toxicity was analysed on pure cultures of Gram-positive and Gram-negative bacteria, nalidixic acid, polymyxin B sulfate, colistin, methyl red, cefotaxim, amikacin, 2-chlorphenol, metronidazole and potassium tellurite were shown to perform best for the selective isolation of coryneform microorganisms; sodium azide, potassium thiocyanate and lithium chloride were not suitable. A new selective agar medium (NPC) for coryneform bacteria containing standard agar, plate count agar or columbia agar together with nalidixic acid (20 mg/l), polymyxin B sulfate (40,000 IU/l) and cycloheximide (100 mg/l) was tested with samples of milk, surface water, waste water and soil. The NPC agar was not inhibitory to micrococci, probably due to their close relatedness with coryneforms. Use of sugar-free nutrient agar (standard agar) restricted growth of Streptococcus faecalis. Pseudomonads, flavobacteria and chromobacteria, which often accounted for 1-5% of the NPC agar resistant Gram-negative rods, could be distinguished from the Gram-positive bacteria due to differences in colony morphology, since on this medium colony shape is not masked by color reactions. The NPC medium was more effective in eliminating Gram-negative bacteria, bacilli, moulds and yeasts than beta phenethyl alcohol media and potassium tellurite media. PMID- 3101315 TI - [Arterial vasospasm as a complication of the prevention of thromboembolism with heparin-dihydroergotamine and its treatment]. PMID- 3101316 TI - [Are animal experiments and clinical prevention of abnormalities possible?]. AB - A important problem of the experimental teratology is the prevention of malformations. In this article first results are published of clinical prevention of clefts in hereditary burden families. Moreover described the present situation of the own experimental-teratological observations. The author found a new protective function against malformations by the nootropicum centrophenoxine. PMID- 3101317 TI - [Cellular and molecular biological aspects in environmental toxicology]. AB - Health effects of substances in the environment are considered from the viewpoint of cellular and molecular biology. There are nephrotoxic effects of cadmium to be discussed as well as mechanisms of carcinogenesis and neurotoxicity. Finally, the influences of noxious substances on lung clearance and immune reactions are demonstrated. PMID- 3101318 TI - [Microbiology of ground water and drinking water]. AB - Groundwater has been considered a safe source for drinking water protected against surface contamination. However, a number of reports about chemical and microbiological contamination have disproved this assumption. Besides hygienical monitoring, little is known about the microbiology of ground- and drinking water. The purpose of this paper is to give a review about the main fields of investigation concerning microbial activity in ground- and drinking-water-action. The hygienical relevant topics are: survival and transport of microorganisms, microbiological degradation of organic pollutants, turn-over of nitrogen compounds, oxidation and reduction of iron and manganese and development of methods for microbiological water examination. PMID- 3101319 TI - A comparison of media for the enumeration of filamentous fungi from aqueduct biofilm. AB - Six media (Czapek, Martin's, Mycological, Nutrient, Sabouraud Dextrose and Sabouraud Maltose), were evaluated for their ability to recover filamentous fungi from aqueduct biofilm. Average filamentous fungal levels detected by the six media ranged from 46-250 CFU/cm2 of biofilm. Of the media tested, Nutrient, Czapek and Sabouraud Dextrose provided the highest relative recoveries. PMID- 3101320 TI - [Standardization of the testing of disinfectants in Europe]. AB - Several European countries have adopted the evaluation of the microbicidal properties of disinfectants in two stages: after some preliminary tests, tests under practical conditions or main tests are carried out, as was described originally in the German guidelines for the testing of disinfectants. Nevertheless in the Anglosaxon countries, the use dilution of products intended for surface and floor disinfection is determined by suspension tests, capacity tests, or carrier tests. In some European countries, however, tests under practical conditions are developed for this purpose, but if these Belgian (B), German (D), French (F) and Dutch (NL) techniques are analysed and compared in their composing elements, great differences are found (Tables 1 to 3). Therefore the Belgian and Dutch tests must be the more severe. Another example of discordance is given in the preoperative disinfection of the surgeons' hand. Between 1973 and 1984 23 different testing techniques were described (Table 4). The differences in technique explain the differences in results obtained. In order to achieve a greater unification of the testing techniques, it is desirable to agree firstly on the requirements of disinfectants. Perhaps it is time to discuss it again. PMID- 3101321 TI - Antibacterial efficacy of Fabry's tinctura on the resident flora of the skin at the forehead. Study of bacterial population dynamics in stratum corneum and infundibulum after single and repeated applications. AB - The in-vivo antibacterial activity of Fabry's tinctura (FT), a 3 w% salicylic acid, 1 w% phenoli liquefacti containing 50 v/v% isopropanol used in dermatology for the treatment of erythrasma, pityriasis versicolor, acne vulgaris a.o. on the human resident skin flora was assessed by a new test method in comparison to 60 v/v% isopropanol. The test method consists of a detergent scrub method (DSM) in combination with the cyanoacrylate method (CAM) thus allowing the quantitative determination of bacterial densities in two depth compartments of human skin, separately for bacterial genera. The most important innovation of this test method is that its arrangement, especially the separate evaluation of the genera of the resident flora, makes it possible to examine the ability of an antimicrobial agent to invade different depth compartments by its bioactivity against the resident flora and to measure short-and-long-term efficacies under physiological conditions. Our findings in 120 volunteers indicate that compared to 60% isopropanol FT is able to reduce bacterial density in superficial and deep skin compartments immediately after a single application equally well, but for a significantly longer period. In repeated applications, 60% isopropanol does not produce a cumulative or long-lasting effect, but it causes an abundant rebound growth of Propionibacterium spp. in the lower skin compartment. FT, however, shows a cumulative antibacterial effect at the surface and in the depth persisting up to four days after the last application. It is concluded that by its salicylic acid and phenolic content FT is an effective drug for the topical antimicrobial therapy of skin diseases. PMID- 3101323 TI - Determination of endotoxins on hypodermic needles by means of a chromogenic Limulus amoebocyte lysate assay. Development of a test model. AB - A test model was developed in order to describe the determination of endotoxins on hypodermic needles in a reliable and reproducible manner. As in all in-vitro experiments one has to be very careful about extrapolating data to in-vivo situations. However by choosing a hydrophilic (Salmonella typhimurium ATCC 14028) and a hydrophobic bacterium (Acinetobacter calcoaceticus var. anitratus RR 8212/113), one could hope to obtain a quite representative idea about the extraction of contaminating gram-negative micro-organisms. Using the proposed extraction procedure and a chromogenic LAL assay as detection system, it was possible to achieve a quantitative idea about the extraction of endotoxins on hypodermic needles. Extracting needles at 19 degrees C during 83 to 98 min produced the highest yield as to the detection of endotoxins from hydrophilic strains. For the detection of endotoxins from hydrophobic strains, the highest yield values were obtained when the extraction was performed at temperatures between 64 and 80 degrees C during 96 to 120 min. However it seems necessary to perform the extractions at least three times in order to obtain reproducible results. In conclusion, using the extraction procedure as described, it is possible to measure endotoxin-like activity, on the inner and outer surface of hypodermic needles in a simple but accurate way, using water as extraction fluid and a chromogenic Limulus Amoebocyte Lysate assay as detection system. PMID- 3101322 TI - [The problem of heat activation of bacterial spores after disinfection with regard to an aerosol method of decontaminating equipment and rooms]. AB - This paper describes investigations on disinfection of germ carriers, contaminated with an alcoholic suspension of Bacillus cereus or Bacillus subtilis. Result of disinfection is compared with that of an additional heat treatment (80 degrees C, 60 min) after disinfection. Besides Formalin, Tegodor forte (Th. Goldschmidt, Essen) and P 3 oxonia active (Henkel KG, Dusseldorf) are tested with different concentration and duration. Heat activation was possible with all three disinfectants. For illuminating the conditions of activation, circumstances of heat action after disinfection with formaldehyde-aerosol have been varied. Heat activation in dry air, moist air and distilled water was not successful. Only in Nutrient Broth (Standard I-Bouillon; Merck, Darmstadt) spores were viable again, after activation. Addition of serum as a protective cover had no influence on the result. Consequences of the results on a disinfection method with formaldehyde-aerosol are discussed. PMID- 3101324 TI - [Decontamination of drinking water taps colonized with Pseudomonas aeruginosa]. AB - Water taps in hospitals are quite often contaminated with Pseudomonas aeruginosa. It is possible that Pseudomonas aeruginosa is disseminated with the water. It seems necessary to disinfect the water taps in order to prevent an endangering of the patients and a contamination of wetted areas. It has been looked for a method of decontamination which could be used under practical conditions. The experimentally contaminated taps could be disinfected in a short time when hot water was lead into the taps. The taps could not be disinfected by heating with a flexible electric heating ribbon. PMID- 3101325 TI - Beryllium toxicity to human, monkey and dog cells in culture. AB - The toxicity of beryllium was evaluated using a mammalian cell culture system. As the ID50 (a fifty per cent inhibitory dose, to growth of cells after 72 h of incubation) values for HEL-R66, KB, Vero and MDCK cells to beryllium were 0.8 X 10(-3) mM, 1 X 10(-3) mM, 0.9 X 10(-3) mM and 1.2 X 10(-3) mM, respectively, there was no remarkable difference in the sensitivity for these cells to beryllium. PMID- 3101327 TI - Hoof and leg traits of Swedish dairy cattle. I. Objective measurements. PMID- 3101326 TI - [Guidelines for testing and rating hand decontamination preparations]. PMID- 3101329 TI - [Capnography--a method for evaluating the ventilation level in general anesthesia in the horse]. PMID- 3101328 TI - Genetic variation in milk acetone in Swedish dairy cows. PMID- 3101330 TI - Carbadox induced changes in aldosterone, sodium and potassium levels in the blood of weaned pigs. PMID- 3101331 TI - [An exact in vitro method for measuring the mucociliary clearance of the rabbit trachea]. PMID- 3101332 TI - Acetylation and hydroxylation of sulphadimidine in the snail Cepaea hortensis. PMID- 3101333 TI - Demonstration of Listeria monocytogenes with the PAP technique in formalin fixed and paraffin embedded tissues of experimentally infected mice. PMID- 3101334 TI - [Features of the functioning of the catecholamine and adrenocortical systems of patients with depression and different degrees of emotional tension]. AB - The catecholamine and adrenocortical systems in 52 patients with depression were studied with regard to the degree of their emotional tension. On the basis of the clinical characteristics of the depressive syndrome the patients were divided into two groups: the stressory hyperergic type (Group 1) and the torpid hypoergic type (Group 2). Some characteristics of the studied systems proved common for both groups: they increased secretion of 11-hydroxycorticosteroids and impairment of the mechanisms of negative feedback in the regulation of adrenocortical activity, as well as a decrease in the excretion of dopamine, adrenaline, and DOPA in the presence of a relative acceleration of catecholamine inactivation. Along with the characteristics common for all the patients studied, the authors revealed a highly significant difference in noradrenaline excretion between Groups 1 and 2: it was normal in Group 1 and decreased three-fold in Group 2. The findings obtained are discussed in the light of the catecholamine hypothesis of depression development. PMID- 3101335 TI - A contribution to the geographical interpretation of biological change. AB - "Geography" has traditionally been assigned the role of handmaiden in evolutionary studies. In this work a different understanding of the relationship between biological change and locational setting is developed: evolution as a dynamic form of spatial interaction. In the causal model presented, adaptive change is portrayed as a negative feedback response contributing to a general spatial-temporal process of resource cycle tightening involving exchanges between the two fundamental structural sectors ("abiotic" and "biotic") of the earth's surface system. As such, it is rejected as "evolution" per se. This position makes it possible to circumvent the "adaptation yields adaptation" circularity, and to view locational circumstances as being evolutionarily causal, yet not deterministic with respect to population-level change. A parallel interpretation of the relation between range and range change and evolution is also implicit; the individualistic hypothesis is thereby superceded by a model of community evolution allowing for individualistic rates of population (adaptive and) range change, but operating on the principle that populations should tend to change range in common directions (as a response to spatially-varying degrees of efficiency of turnover of resources vital to biotic sector function). This in turn leads to the possibility of normative biogeographic modelling. Comment is also made on the relationship of the present understanding to disequilibrium and dynamic equilibrium interpretations of evolutionary change, and to human cultural evolution. PMID- 3101336 TI - Exchange of occluded, tunnelled, subclavian central venous catheters. A technique reusing the existing tunnel. AB - A technique for the exchange of occluded, tunnelled, subclavian venous catheters reusing the existing tunnel is described. It was successfully used 14 times in 5 patients needing permanent parenteral nutrition at home, in whom insertion of a new catheter by another route would have been cumbersome and hazardous. The tunnel was opened below the clavicle, and the catheter clamped. The catheter was then cut close to the tunnel exist, and its distal part removed centrally through the opening at the clavicle. A guide wire was simultaneously pulled through. An introducer cannula was placed over the central part of the catheter into the subclavian vein, and the occluded catheter was withdrawn and a new one inserted. The latter was then guided through the tunnel by the guide wire. The catheter was then fixed, and the wound was closed and dressed. Prophylactic cloxacillin was given i.v. for 3 days. No bleeding, pulmonary embolism, local infection or sepsis were observed. PMID- 3101337 TI - Failure to induce puberty in a man with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism by pulsatile administration of low-dose gonadotropin-releasing hormone. AB - To elucidate the mechanism of hypogonadotropic hypogonadism in a patient with X linked congenital adrenal hypoplasia, we studied the effects on serum LH and FSH of repeated iv administration of GnRH (400 micrograms, over 2 h, once a day, for 14 consecutive days), pulsatile sc administration of GnRH (5 micrograms every 90 min during days 1 approximately 56, 10 micrograms every 90 min during days 57 approximately 91) and an iv bolus injection of 10 mg of naloxone. The repeated administration of GnRH restored the hyporesponsiveness of serum FSH and increased serum testosterone level from less than 1.0 to 1.7 nmol/l, but the impaired LH response to the standard GnRH test was not improved. The pulsatile administration of GnRH for 91 consecutive days did not induce a clinical or a biochemical change of puberty. Serum testosterone remained undetectable less than 1.0 nmol/l, the hyporesponsiveness of serum LH was not improved, but basal FSH level was significantly increased and the impaired FSH response to the standard GnRH test was slightly improved. Naloxone had no effect on serum LH or FSH before or during the pulsatile administration. We conclude that hypogonadotropic hypogonadism in our patient is due to the pituitary dysfunction and that the endogenous opioid peptides may not play a role in the mechanism of inhibited gonadotropin secretions. PMID- 3101338 TI - The pituitary TSH response to TRH is inversely related to the plasma TSH concentration and directly related to the pituitary TSH content during hypothyroidism in the rat. AB - We studied the effects of degree and duration of hypothyroidism on the pituitary TSH concentration and the pituitary TSH secretory response to TRH. Varying degrees of hypothyroidism were achieved in thyroparathyroidectomized rats (THYREX) by continuous sc infusion of T3 (0.2, 0.3, 0.4, or 0.5 microgram/100 g X day) or T4 (0.6, 1.2, or 1.8 microgram/100 g X day). While T3 was more potent than T4, both resulted in a dose-dependent suppression of the post-thyroidectomy rise in TSH. After 7 or 14 days of severe hypothyroidism (nonreplaced THYREX rats) the pituitary TSH secretory response to TRH (250 ng/100 g body weight, iv) was found to be decreased when compared to that of euthyroid rats. Decreasing the degree of hypothyroidism increased the pituitary secretory response to TRH and the pituitary TSH content. The results indicate that in the hypothyroid rat: severe hypothyroidism results in a blunted pituitary TSH response to TRH through 14 days after thyroidectomy, at 7 and 14 days after thyroidectomy the pituitary TSH response to exogenous TRH is inversely related to the basal plasma TSH concentration, the pituitary TSH concentration increases with the duration of hypothyroidism, the pituitary TSH content is increased by low rates of thyroid hormone replacement, and the pituitary TSH response to exogenous TRH is directly related to the pituitary TSH content. PMID- 3101339 TI - Serum concentrations of thyrotropin, thyroxine, triiodothyronine and thyroxine binding globulin in female endurance runners and joggers. AB - The effects of endurance training and season on the function of the anterior pituitary-thyroid axis were studied in 18 female runners and their 12 controls, and in 13 joggers and their 11 controls in Northern Finland, with a large seasonal difference in environmental factors. The serum concentrations of thyrotropin (TSH), thyroxine (T4), free thyroxine (fT4), triiodothyronine (T3), thyroxine binding globulin (TBG) and oestradiol (E2) were measured during one menstrual cycle in the light training season (autumn) and in the hard training season (spring). The responses of TSH to intravenous TRH stimulation were also measured in the luteal phase of the cycle during the hard training season. Endurance running did not affect the basal or TRH-stimulated serum TSH concentrations, while those of T4 and fT4 in runners were lowered in both seasons and that of T3 in the light training season in relation to control subjects. The serum concentrations of TBG were also significantly lower in runners than their controls in the luteal phase in both seasons. The effect of jogging on thyroid hormones was less pronounced. Serum concentrations of TSH, T4, fT4, T3 and TBG were generally slightly higher in spring than in autumn. Strenuous endurance training seems to have minor changes on the function of the thyroid gland. Depressed T4 levels in runners may rather be due to lowered TBG levels than due to direct effect of training. In spring the function of anterior pituitary thyroid axis is more active than in autumn. PMID- 3101340 TI - Growth hormone response to growth hormone-releasing hormone in normal and uraemic children. Comparison with hypoglycaemia following insulin administration. AB - The uraemic syndrome is characterized by several endocrinological disturbances. This study was undertaken in order to evaluate the GH response to growth hormone releasing hormone (GRH) in children with chronic renal failure (CRF) and to compare the results with those observed after insulin hypoglycaemia. Twenty-two children with CRF, 10 undergoing continuous ambulatory peritoneal dialysis (CAPD) and 12 on conservative treatment (CT), age ranges 2-15 years, were studied and the data were compared with those from 14 children with normal renal function and normal hormonal behaviour, affected by short stature (NC), and those form 13 healthy adult volunteers (NA). The GRH test (l micrograms/kg body weight, iv) was carried out in 8 CAPD, 8 CT, 9 NC and 10 NA subjects. The blood samples were taken every 30 min for 3 h in CAPD and CT and for 2 h in NC and NA starting at 09.00 h. The following hormones were measured: GH, LH, FSH, Prl, TSH and cortisol (F). The insulin test (0.1 U/kg body weight, iv) was carried out in 5 CAPD, 5 CT, 10 NC and 9 NA on blood samples taken every 30 min for 2 h, measuring GH and glycaemia. No adverse effects were observed after the infusion of GRH. GRH administration induced a prompt response in all subjects, but GH plasma levels were significantly higher in uraemic children than in adults (peak value of 43.5 +/- 8.2, 45.0 +/- 8.4, 27.8 +/- 6.0; 13.5 +/- 2.6 micrograms/ml in CAPD, CT, NC and NA, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101341 TI - The effect of 1,25-dihydroxy-cholecalciferol on the TRH induced TSH release in rats. AB - The effect of 1,25-dihydroxy-vitamin D3 (1,25-(OH)2-D3) on the TRH induced TSH release was investigated. Wistar rats were injected with 1,25-(OH)2-D3 (0.05 microgram/kg/day) for three days, and TRH was injected iv on the third day. Blood was drawn every 10 min during the following 40 min, and TSH was determined. The TSH release was significantly higher in rats treated with 1,25-(OH)2-D3 than in controls. The rats treated with 1,25-(OH)2-D3 were hypercalcaemic and thus, in order to find out if the effect was mediated through hypercalcaemia rats treated as above, were infused with EDTA (30 mg/kg/100 min) starting 60 min before the TRH test. This treatment made the rats normocalcaemic, and the significant increase in the TSH release was still seen in the 1,25-(OH)2-D3 treated rats as compared to controls. The results thus indicate that 1,25-(OH)2-D3 enhances the TRH induced TSH release and that the effect is not mediated through an increase in the serum calcium concentration at the time of the TRH test. In order to find out if the effect could be mediated by changes in intracellular calcium the rats were treated with the calcium antagonist verapamil (25 mg/kg/day) and the adrenergic blocker propranolol (5 mg/kg/day) alone or together with 1,25-(OH)2 D3. In rats treated with verapamil or propranolol alone or 1,25-(OH)2-D3 + propranolol, no effect was observed on the TRH induced TSH release. Verapamil + 1,25-(OH)2-D3 significantly increased the TSH release as compared to both controls and rats treated with 1,25-(OH)2-D3 alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101342 TI - Tamoxifen does not block the inhibitory effect of testosterone on FSH release in rats. AB - The aim of the present experiments was to analyze whether the inhibitory effect exerted by testosterone on FSH release might be mediated by the intracerebral transformation of the hormone into oestrogenic metabolites. Advantage has been taken of the availability of the potent antioestrogen tamoxifen. Two series of experiments have been performed. In the first one, adult male rats have been castrated and submitted, beginning immediately after surgery, to a 6-day treatment with testosterone propionate (2 mg/rat/day), tamoxifen (50 or 200 micrograms/rat/day) or testosterone propionate (2 mg/rat/day) plus tamoxifen (either 50 or 200 micrograms/rat/day). In the second experiment, adult male rats have been castrated and submitted to the same 6-day treatments, beginning 4 weeks following orchidectomy. In both experiments, the animals were killed 24 h after the last injection, and serum levels of FSH and LH have been measured by radioimmunoassays. The results have clearly shown that, in both experiments, the administration of testosterone results in a significant decrease of serum FSH and in a total suppression of LH release. The administration of tamoxifen, in either dose, does not modify the elevated serum FSH and LH levels present in the orchidectomized animals, and does not antagonize the inhibitory effect on FSH and LH secretion exerted by the concomitant treatment with testosterone propionate. It is concluded that testosterone inhibits FSH secretion in orchidectomized rats acting as such, and not following aromatization to oestrogens. PMID- 3101343 TI - Gene patterns of immunoglobulin heavy chain in various cell lines and lymphoid malignancies. PMID- 3101344 TI - Clinical studies on the relationship of vascular complications to platelet functions and plasma factor VIII levels in connective tissue (collagen) diseases. PMID- 3101345 TI - Protein and gene structure of autoantibodies in the study of autoimmune disease. AB - The development of the hybridoma technology and the recent advances in molecular biology have opened new directions in the study of autoimmune mechanisms. Monoclonal autoantibodies can now be isolated and their structural elements may be studied in detail. In addition, the immunoglobulin genes which code for the production of antiself antibodies may now be cloned and analyzed for their structure and regulation in normal and autoimmune individuals. Initial results in this new field of molecular immunology are reviewed in this article, and their implications for the understanding of autoimmune phenomena are discussed. PMID- 3101346 TI - High levels of a common anti-DNA idiotype (16/6), a genetic marker for SLE. AB - Six out of 8 healthy first-degree relatives of a patient with systemic lupus erythematosus (SLE) had very high serum levels of a common anti-DNA idiotype (16/6). In this family an additional sister developed SLE, and all members were heterozygous for C4 deficiency. Measurements of common autoantibody idiotypes may contribute to the understanding of the genetics of autoimmune diseases. They might be found useful in detecting healthy subjects prone to the development of an overt clinical state. PMID- 3101347 TI - HLA antigens, blood groups and immunoglobulin levels in idiopathic thrombocytopenic purpura. AB - Thirty-three patients with idiopathic thrombocytopenic purpura (ITP) were tested for HLA-A, B and C antigens, platelet antibodies, immunoglobulin levels and ABO blood groups. With one exception, ITP proved not to be significantly associated with the HLA antigens studied; an increased frequency of HLA-A28 was found in chronic ITP patients (50 vs. 18.7% in the control population). An increased incidence of blood group A was found in ITP patients (64 vs. 37.98% in the control population), especially in those with acute ITP (84.7%). A significant reduction of IgG levels was noted in patients with chronic ITP, while below normal levels of IgA were found in both chronic and acute ITP patients. There was no difference in levels of IgM. Circulating platelet isoantibodies were demonstrated in 67.6% of the ITP patients. No correlation was demonstrated between the presence of platelet antibodies, immunoglobulin levels of HLA antigens. PMID- 3101349 TI - Platelet survival in myelodysplastic syndromes. AB - A platelet survival study with indium-111 oxine was performed in 6 patients with a myelodysplastic syndrome. A markedly shortened platelet life-span (range 0.50 2.65 days; normal 6.5-12 days) was obtained in each case. Platelet production ranged from 53,100 to 430,800 platelets/mm3/day (normal 66,200 +/- 14,600). A second isotopic study was performed in 1 case with platelets from a normal compatible donor. The nearly complete normalisation of the platelet life-span (from 0.85 to 5.50 days) indicates an intracorpuscular origin of the defect. PMID- 3101348 TI - Capping of leukemic cells with monoclonal anti-HLA-A,B,C related to prognosis in childhood acute lymphoblastic leukemia. AB - Capping of leukemic cells with a monoclonal antibody against HLA A,B,C determinants was studied in 53 cases of childhood acute lymphoblastic leukemia (ALL). Determination of the percentages of capped cells after different times of incubation with anti-HLA A,B,C show that T ALL and common ALL do have quite different kinetics of HLA capping. In T ALL all cases reach levels of percentage of capped cells above 30%, in common ALL only 11 of 31 cases cap well. Dilution of the antiserum in 6 common ALL cases results in an increase of capped cells, but the original kinetics of the common ALL capping remain. ALL cases with capping curves above 30% have a worse prognosis (shorter continuous complete remission) than cases with capping curves below 30% in the total group as well as in the non-high-risk group. PMID- 3101350 TI - Low-dose cytosine arabinoside in the treatment of relapsed and refractory acute non-lymphocytic leukaemia. AB - Low-dose cytosine arabinoside (ARA-C) induced complete remissions in 6 of 10 patients with acute non-lymphocytic leukaemia (ANLL) who were either refractory to combination chemotherapy with anthracyclines and conventional doses of ARA-C, or were in relapse. Three patients relapsed after 4, 19, and 20 months, whereas 3 patients are still in remission for 8-46 months. Low-dose ARA-C was rather non toxic and may be preferable to more intensive and toxic regimens in the therapy of refractory and relapsing patients with ANLL. PMID- 3101351 TI - Additional chromosomal abnormalities to Ph during the clinical course in patients with acute lymphoblastic leukemia. AB - Cytogenetic findings obtained during the clinical course in two patients (one child and one adult) with Ph-positive acute lymphoblastic leukemia (ALL) are reported. Chromosomal abnormalities in addition to Ph chromosome were detected in both patients. At the beginning of the disease, such abnormalities consisted of the trisomy of chromosome 1 and monosomy of chromosomes 8 and 9, with a sub-line 45, XY, Ph, -8 in the child; in the adult patient a hyperdiploid clone with 57-59 chromosomes and Ph duplication was present. At relapse, the same karyotypic anomalies reappeared in the child, whereas in the adult a high frequency of chromosomal rearrangements, such as ring and dicentric chromosomes, was observed after cranial irradiation. The occurrence of chromosomal abnormalities additional to Ph during the clinical course in ALL patients is discussed, taking into account data from the literature concerning the lymphoid blastic crisis in chronic myeloid leukemia patients. PMID- 3101352 TI - Diminished extractable spectrin in the erythrocytes of a patient with 'sporadic' hereditary spherocytosis. AB - A 51-year-old white man of Irish extraction was found to have apparent 'sporadic' hereditary spherocytosis with a reticulocyte count of 6%. Twelve of his 13 siblings were examined and found to be haematologically normal. The patient's erythrocytes were found to have a diminished amount of spectrin as compared to his siblings and to unrelated controls. It is suggested that the proband may represent either a new mutant or possibly double heterozygosity for two inherited biochemical variants of the red cell membrane skeleton which individually give no haematological abnormalities. PMID- 3101353 TI - Bone marrow disturbances of iron utilisation: cytomorphological diagnostic in chronic alcohol abuse. AB - 45 consecutive patients with chronic alcohol abuse up to the day before admission were examined to determine to what extent the investigation of bone marrow smears is suitable for recording the abuse of alcohol and for monitoring the abstinence from alcohol. Using Prussian blue staining, disturbances of iron utilisation subdivided into four degrees of seriousness were detected in 91% (41 out of 45) of subjects, whereas abnormal vacuolisation of red and/or white precursors occurred in only 38% and megaloblastic marrow in 27% of patients, respectively (p less than 0.005). Abstaining from alcohol caused a significant decrease of sideroachrestic signs (p less than 0.005) within a few days. PMID- 3101354 TI - Cytogenetics in nutritional megaloblastic anaemia: prolonged persistence of chromosomal abnormalities in lymphocytes after remission. AB - Chromosomal studies were performed in phytohaemagglutinin-stimulated cultures of lymphocytes and in bone marrow cells without culture from 115 patients with megaloblastic anaemia resulting from nutritional deficiency of folate and vitamin B12. Essentially similar chromosomal abnormalities were observed in the two cell lines. These were characterized by striking morphological aberrations such as elongation and despiralization (uncoiling or incomplete contraction), increased frequency of chromosome breakage and centromere spreading. Numerical abnormalities, chromatid exchanges and translocations were virtually absent. Autoradiographic studies of chromosomes after pulse-labelling with 3H-thymidine during the terminal 6 h of phytohaemagglutinin-stimulated lymphocyte cultures revealed a differential pattern of distribution of the radionucleotide in the chromosome of megaloblastic lymphocytes as compared to those from normal lymphocytes. Repeated chromosomal studies were done in 65 of these patients at various intervals after starting therapy with the deficient vitamins. After 48 h of therapy, chromosomal abnormalities were remarkably reduced in the bone marrow; but many of these morphological chromosomal changes (i.e. despiralization and breaks) persisted in the lymphocytes of a significant proportion of patients for variable periods up to 6-12 months after haematological remission resulting from therapy with the deficient vitamins. These abnormalities did not, however, persist after remission in those patients who had repeated episodes of infections. PMID- 3101356 TI - Erythropoietin levels in heterozygous alpha-thalassemia. AB - In guinea pig bone marrow cultures with heterozygous alpha-thalassemic serum, 59Fe uptake values are elevated above iron values of cultures with serum of normal subjects. These results show that erythropoietin (EP) activity values in heterozygous alpha-thalassemia are comparable to those previously observed by ourselves in heterozygous beta-thalassemia despite of the different Hb concentration in these thalassemic syndromes. This points to the existence of signals which regulate Ep synthesis independently of Hb levels. PMID- 3101355 TI - Increased phagocytosis of Plasmodium falciparum-infected erythrocytes with haemoglobin E by peripheral blood monocytes. AB - Erythrocytes from subjects with homozygous and heterozygous haemoglobin E (HbE) infected with Plasmodium falciparum in vitro were phagocytosed to a greater extent by normal human monocytes than infected erythrocytes from normal subjects. Susceptibility to phagocytosis was maximal when the parasites developed to trophozoite and schizont stages in both normal and patients' erythrocytes. The increased susceptibility of P. falciparum-infected HbE erythrocytes to phagocytosis by monocytes may play a role in protection against malaria. PMID- 3101357 TI - Haemoglobin Presbyterian [beta 108 (G 10) Asn----Lys] in a Spanish family. AB - Clinical, haematological and biochemical aspects of a new family with heterozygous haemoglobin Presbyterian [beta 108 (G 10) Asn----Lys] are described. It could be readily separated by isoelectric focusing, DEAE-cellulose chromatography and by cation exchange high-performance liquid chromatography (HPLC). The characterization of this mildly unstable haemoglobin was made by reverse-phase HPLC. This is the fourth family with Hb Presbyterian so far described. PMID- 3101358 TI - Secondary refractory anemia with excess of blasts in transformation terminating as acute lymphoblastic leukemia. AB - A case of refractory anemia with an excess of blasts in transformation, secondary to irradiation, and leading ultimately to acute lymphoblastic leukemia, is presented. Commonalities and differences between acute lymphoblastic and nonlymphoblastic leukemias secondary to radiotherapy are discussed. PMID- 3101359 TI - Scabies-associated angioimmunoblastic lymphadenopathy. AB - A systemic disorder characterized by fever and reactive lymphadenopathy developed in a patient with scabies infestation. Regression of all clinical symptoms and signs occurred after antiscabies therapy. Two months later, the whole clinical picture reappeared concomitantly with scabies reinfestation. Subsequent lymph node biopsy demonstrated typical angioimmunoblastic lymphadenopathy (AILD). It is plausible that persistent antigenic stimulation caused by scabies infection was of pathogenetic importance in the induction of the syndrome of AILD. Infectious agents should be considered and looked for in patients with AILD, since they may play a role in the evolution of this disease. PMID- 3101360 TI - Variations in morphological and immunological blast cell phenotype in a case of acute leukaemia with t(4;11) translocation. AB - A case of acute leukaemia with t(4;11) chromosomal abnormality in a 28-year-old woman is reported. At diagnosis, two blast cell populations were seen: 60% of the cells were small cells with lymphoid morphology, 40% were large cells with monocytic morphology. Cytochemical examination was consistent with acute myeloid leukaemia (peroxidase-positive in 10% of the cells), but surface markers were those of common acute lymphoblastic leukaemia (CALLA, B4, TdT-positive, but My7-, My9- and OKM1-negative). Five days after diagnosis, although the only treatment had been platelet transfusions, there was a change in morphological and immunological phenotype: 40% of the cells were lymphoid and 60% monocytic. Lymphoid markers were expressed in only 20-40% of cells, and myeloid markers appeared on up to 60% of cells. We conclude that t(4;11) leukaemia could originate in an undifferentiated progenitor cell, which can undergo further differentiation into lymphoblasts or monoblasts, and that we were able to observe this in vivo differentiation in our patient. PMID- 3101361 TI - Multiple blastic transformations in the course of chronic granulocytic leukaemia. AB - A 14-year-old boy with Philadelphia chromosome-positive chronic granulocytic leukaemia underwent morphologically distinctive blastic transformation on 3 separate occasions. The first was clearly lymphoblastic, the second was associated with meningeal leukaemia and was morphologically biphenotypic, expressing mixed myeloid and lymphoid features, while the third was characterised by extreme thrombocytosis and megakaryoblastic proliferation. The classical t(9:22) Philadelphia chromosome remained constant throughout the illness, but the additional cytogenetic changes that occurred with the first transformation were abolished with response to conventional therapy for lymphoblastic leukaemia. A total of 19 months of good-quality life was achieved, but on the third occasion, the boy died from intracranial haemorrhage before treatment could be initiated. PMID- 3101362 TI - Myeloproliferative disorder during the course of multiple myeloma. AB - A patient with multiple myeloma who developed a myeloproliferative disorder 6 years after initial diagnosis is described. The 2 disorders coexisted for 3 years. Possible explanations for this occurrence are discussed. PMID- 3101363 TI - Solitary plasmacytoma of the bone in a case of Hodgkin's disease. AB - This report describes a case of solitary plasmacytoma of the bone which occurred in a 35-year-old male 3 years after mantle field irradiation for Hodgkin's disease, nodular sclerosing, stage IA. The possible significance of this rare association is discussed. PMID- 3101364 TI - Note to the paper 'Red cell superoxide dismutase is increased in iron deficiency anemia'. PMID- 3101365 TI - Therapeutic quality control leading to further clinical assessment of oral anticoagulation. AB - Oral anticoagulant therapy has been practiced for 40 years but we still do not have definitive evidence of its value. Early clinical trials are now discounted due to the varying quality and lack of standardisation of the thromboplastins then available. There was also no statistical evidence that therapy was adequately maintained. We now have sensitive and reliable thromboplastins and there is an international standardisation of calibration and of reporting prothrombin time. With therapeutic quality control of oral anticoagulation and the so treated patients clinical assessed, we might hope that definitive evidence of the value of this therapy would result. PMID- 3101366 TI - Pregnancy and autoimmunity. AB - Clinical immunology, already a subspecialty within internal medicine, is achieving increasing importance within the field of reproductive medicine. The recent recognition that subclinical autoimmune processes may be causally related to repeated early-pregnancy loss has allowed for the conceptional connection between the fields of infertility and obstetrics. While the immunology of infertility has been in mainstream clinical practice for years, clinical application of immunologic knowledge in obstetrics has somewhat lagged behind. The review presented here is an attempt to summarize recently recognized immune processes which affect pregnancy. Pregnancy seems particularly susceptible to immunologic interference during the very early and very late stages of gestation. During early pregnancy subclinical autoimmune processes seem capable of causing both pregnancy loss as well as congenital fetal abnormalities such as congenital heart block. Very acutely occurring immune processes in late pregnancy can endanger both maternal and fetal life and need therefore to be clinically recognized as such. The considerable progress in the clinical immunology of pregnancy made over the last few years needs to be continued by defining the clinically observed processes immunologically and biochemically in more detail. The thus obtained knowledge will not only benefit the clinical management of immunologically affected pregnancy, but will also enhance the general understanding of many far wider-reaching immunological processes. After all, pregnancy represents an unique model of nature. PMID- 3101367 TI - Frequency of attendance at anticoagulant clinics. AB - The frequency of clinic attendance of long-term anticoagulant patients varies considerably between centres. At this hospital, patients with a record of good anticoagulant control are seen every 3 months, which is double the currently recommended period. To assess this policy, the British ratio of 461 patients on long-term anticoagulants was examined at each visit over the last year. 46% of patients had been seen only at 3-month intervals over the last 5 visits and their anticoagulant control was excellent, 88% of visits falling in the British ratio range 2.0-4.0. It is concluded that amongst chronic anticoagulant patients a significant subgroup may be identified who can safely be monitored at 3-monthly intervals, and this has considerable cost implications. PMID- 3101368 TI - Lupus anticoagulant and anticardiolipin antibodies in systemic lupus erythematosus. AB - The lupus anticoagulant (LA) is an acquired autoantibody of the IgG or IgM type that acts on platelet factor III, inhibiting the generation of the prothrombin activator complex. It is prevalent in 5-10% of SLE cases and, in contradistinction to the name anticoagulant, it may be associated with thrombotic events, recurrent abortion or intrauterine death. Anti-cardiolipin antibody like LA, is an anti-phospholipid antibody and also causes recurrent thrombotic events. Mention has been made of a possible cross-reactivity between anti-phospholipid antibodies and anti-DNA antibodies. The optimal treatment for this problem is at present unknown. PMID- 3101369 TI - Circulating anticoagulant in systemic lupus erythematosus: clinical manifestations. AB - The correlation between the presence of lupus circulating anticoagulant (LCA) and the incidence of thromboembolic phenomena was evaluated in 66 systemic lupus erythematosus (SLE) patients. Our criteria for the presence of LCA included an elevated LCA index and a prolonged recalcification time. Thirty-two patients (48%) fulfilled these criteria (group A). The incidence of thromboembolic phenomena, recurrent abortions and involvement of the nervous system was higher in group A patients than in SLE patients without LCA (group B). Moreover, 16 patients of group A who exhibited also a positive thromboplastin inhibition test associated with a markedly elevated LCA index, manifested higher incidence of severe thromboembolic phenomena. Early detection of LCA has important therapeutic implications. We suggest that the presence of LCA should be recognized as one of the criteria for the diagnosis of SLE. PMID- 3101370 TI - Autoantibodies, idiotypes, anti-idiotypes and autoimmunity. AB - The establishment of mouse and human monoclonal anti-DNA antibodies is described. Common idiotypes were identified on these antibodies employing monoclonal (mouse) and polyclonal anti-idiotypic antibodies. The significance of the presence and titer of the common idiotypes as clinical activity marker was examined in patients with systemic lupus erythematosus. Based on Jerne's network theory [Ann. Immunol. 125c: 373-389, 1974], naturally occurring anti-idiotypic antibodies to anti-DNA antibodies were reported. The utilization of this information to understand autoimmunity is discussed. PMID- 3101371 TI - [Effect of ganglionectomy (superior cervical ganglia) at normal temperature and exposure to cold on the circadian rhythm of liver glycogen and blood glucose levels of the Wistar rat with regard to the pineal gland]. AB - Liver glycogen content and blood glucose level of 80 male Wistar rats were measured 4 times a day, 30 d after following surgeries: sham-operation without exposure to cold, sham-operation with exposure to cold (283 K, 72 h before killing), extirpation of the ganglia cervicalia superiora (GX) without exposure to cold, extirpation of the ganglia cervicalia superiora with exposure to cold (283 K, 72 h before killing). Exposure to cold alone as well as GX with and without exposure to cold modify the unimodal daily patterns (curves were calculated by means of empirical regression) of liver glycogen content and blood glucose level: there are changes from contrary localization of the maxima (and minima) of both, liver glycogen content and blood glucose level (exposure to cold alone) to nearly equal localization (GX alone). Compared to control group, all surgeries reduce the liver glycogen content statistical-significantly and also enhance the blood glucose level. Combination of GX with exposure to cold shows the strongest effect. In this case, the influence of GX is visible, but the effect is not significantly different from this of exposure to cold alone, which causes a high activation of the metabolism. To the contrary, a statistically significant influence is to be seen after GX alone, but the effect is lower than this one of exposure to cold. Extirpation of the ganglia cervicalia superiora and the resulting sympathetic denervation of the pineal gland is answered by comparable reactions of the investigated parameters as the extirpation of the pineal gland itself (90 d post operationem). Diminuation of liver glycogen content and enhancement of blood glucose level characterize the influence of gangliectomy (30 d post operationem) in this way, that the ratio of effect of factors causing hypo- and hyperglycemia is changed in favour of the latter. PMID- 3101372 TI - [Ultrahistochemical detection of PAS-positive substances in the oviduct epithelium of the aging woman]. AB - The ultrahistochemical findings show that, in the oviductal epithelium of the ageing woman, periodate reactive substances are detectable in ciliated and nonciliated cells. These periodate reactive particles have different intracellular localization and distribution patterns. Besides, cells are found in the epithelium, which either contain only few periodate reactive material or react negatively. These cells appear singularly or in groups. PMID- 3101373 TI - [Morphological and biochemical changes in the pars obliqua of the vastus medialis muscle in degenerative disorders of the knee joint]. AB - Using 34 muscle specimens from the pars obliqua of the vastus medialis muscle of patients with a clinically manifest patellar chondropathy and of those suffering from a gonarthrosis in various positions (cut biopsies under operation), we depicted the slow-twitch (ST) and the fast-twitch (FT) fibres histochemically and ascertained morphometrically the fibre distribution, the areas of the FT- and the ST-fibres as well as the relative fibre volume of the FT-fibres. Furthermore, we determined biochemically the total activity of the enzymes PGK and of the MDH, according to Bergmeyer (1970). By means of the electrophoresis, we determined the isoenzyme pattern of the LDH from simultaneously cut material (Agar-Agarose technique). The mathematical date processing was made by means of the cluster- und discriminance analysis. The results show that the "rule member" (pars obliqua m. vast. med.)--in order to maintain the orthograde gliding motion of the patella in the course of the development of degenerative joint illness--experiences extreme structural and biochemical changes caused by modifications within the neuromuscular motor control pattern. This becomes evident by a FT-hypertrophy at the beginning of the intraarticular disorders and by the increasing development of the "neurogeneous tissue syndrome" with partly fascicular FT-atrophy in cases of progressive degenerative joint processes. PMID- 3101375 TI - Endocrine cells in adenocarcinomas and their prestages in the glandular stomach and duodenum of rats after MNNG administration. Histochemical, electron microscopical and radioimmunological studies. AB - Tumours of the glandular stomach and upper small intestine were induced in rats by oral administration of MNNG. In most cases the lesions were identified histologically as adenocarcinomas and their prestages, such as polypeous and downward growing adenomatous hyperplasias. Out of 48 adenomatous hyperplasias and adenocarcinomas of the stomach and 24 well differentiated adenocarcinomas of the small intestine, we observed argyrophilic cells in nearly the half of the cases. Endocrine cells were also identified by electron microscopy. The frequency of endocrine cells was reduced with decreasing degree of tissue differentiation. In poorly differentiated carcinomas, including signet ring cell carcinomas, no argyrophilic cells were found. Out of 10 adenomatous hyperplasias and tumours of the stomach investigated immunohistochemically, 5 cases showed gastrin producing cells. Most of these animals were radioimmunologically characterized by strongly elevated serum gastrin levels. Derivation and potential relevance of the endocrine cells in tumours are discussed. PMID- 3101376 TI - Modern physical methods for analysing elements and structures in histochemistry. AB - Chemical analysis supported to a greater and greater degree by physical principles and measurement techniques offers some advantages for application in biomedical research and is able to complete histochemical procedures in elemental analysis. The described methods, such as electron-probe X-ray microanalysis, Auger electron spectrometry, cathodoluminescence analysis, electron diffraction, secondary ion mass spectrometry, electron spectrometry for chemical analysis, laser microprobes based on emission spectrometry, mass spectrometry and luminescence spectrometry yield qualitative and quantitative information about the inorganic (and organic) constituents and their distributions of subcellular microvolumes of biological tissues. Information content, figure of merit, applications, and limitations of these methods, and the special preparation techniques of biological materials are discussed. PMID- 3101374 TI - [Immunohistochemical detection of acid cysteine proteinase inhibitors in lymphatic infiltrates of the thyroid gland]. AB - Thyroid tissues containing lymphoid secondary follicles were studied immunohistochemically for the presence of acid cysteine proteinase inhibitor (ACPI). Reticulum cells in the lymphoid secondary follicles, mainly dendritic reticulum cells, exhibited a positive reaction. In addition, in 2 cases a positive reaction could be detected in some of the thyroid epithelial cells, adjacent to the lymphoid secondary follicles. The possible function of ACPI generally and its role in the function of those cells containing it, is discussed. PMID- 3101377 TI - Immunohistochemical study of S-100 protein and neuron specific enolase (NSE) in melanocytes and the related tumors. AB - Normal human skin, malignant melanoma, nevocellular nevus, blue nevus, nevus of Ota and mongolian spot were immunohistochemically investigated on the localization of S-100 protein and neuron specific enolase (NSE). Tissues were fixed with buffered-formalin, processed with routine procedure and examined by the ABC technique. All cases of malignant melanoma and nevocellular nevus showed a relatively high amount of S-100 protein, but NSE was scantly demonstrated on about the half cases of these tumors. Blue nevus, nevus of Ota and mongolian spot revealed the presence of a small amount of S-100 protein and NSE on the half cases. Normal melanocytes were devoid of S-100 protein and NSE. Our results suggest that S-100 protein is the useful marker for diagnosis of malignant melanoma, and immunoreactive intensity for S-100 protein represents the differentiation of neural crest derived melanogenic cells and tumors. PMID- 3101379 TI - Improving patient care for the elderly through a geriatric consultation team. PMID- 3101380 TI - Elder abuse. PMID- 3101378 TI - Cytochemistry of circulating lymphocytes in diabetes mellitus with and without retinopathy and in newly diagnosed type I (insulin dependent) diabetes. AB - Cytochemical studies have been performed on peripheral blood lymphocytes of 68 diabetic subjects, with various conditions of metabolic control, and 15 newly diagnosed insulin-dependent diabetic patients. 20 patients of the 1 group had diabetic retinopathy. In diabetic patients periodic acid Schiff positivity, acid phosphatase, and N-acetyl-beta-glucosaminidase activities of lymphocytes are fairly impaired, particularly in insulin-dependent diabetes. Concerning the alpha naphthyl-acetate-esterase activity, the percentage of positive cells with coarse granules is significantly reduced (p less than 0.001) in diabetic patients as compared to controls, without difference related to age and sex. These abnormalities are more evident in patients with poor glyco-metabolic control. In patients with newly diagnosed insulin-dependent diabetes we have found a further decrease in alpha-naphthyl-acetate-esterase activity, and an increase in acid phosphatase and N-acetyl-beta-glucosaminidase activities. Cyto-enzymatic activities are not significantly different in subjects with diabetic retinopathy. The results of peripheral lymphocyte enzymatic activities in diabetics could be related to a depression of the cell-mediated immunity and could enhance the infections risk of these patients. Furthermore our data show an altered immunological balance in subjects with newly diagnosed type I diabetes. PMID- 3101381 TI - Utilizing Parse's theory of man-living-health in Mrs. M's neighborhood. PMID- 3101382 TI - Career selection: planting the seed for gerontological nursing. PMID- 3101383 TI - Inhibition of phrenic nerve activity during positive-pressure ventilation at high and low frequencies. AB - A study was made to determine whether the ventilatory pattern, in terms of ventilatory frequency, insufflation period and end-expiratory pressure, influences the arterial blood gas level at which central inspiratory activity is inhibited, and whether further expansion of the lung changes this activity. This was accomplished by measuring arterial pH and blood gases, and intratracheal, intrapleural and transpulmonary pressures, at the setting of positive-pressure ventilation causing inhibition of phrenic nerve activity in chloralose anaesthetized cats. Spontaneous breathing movements were prevented by muscle relaxation. Ventilatory frequencies of 15-120 breaths per minute (b.p.m.) were studied at at least two different insufflation times. A volume-controlled ventilator with a large compressible volume was used in the frequency range 15-45 b.p.m. and a constant flow respirator with a low-compressible volume in the range 45-120 b.p.m. A much lower PCO2 was needed for phrenic nerve activity to be inhibited at a ventilatory frequency of 15 b.p.m. than at higher frequencies. At ventilatory frequencies between 30 and 120 b.p.m. inhibition could be achieved at a higher PCO2, within the normal range. The inhibition of phrenic nerve activity tended to be less stable when PEEP was added during ventilation with a long insufflation period, but PEEP did not influence the arterial blood gas level at which inhibition occurred. In the lower frequency range of 15-30 b.p.m., inspiratory activity was observed with bursts at the same rate as the insufflations given by the ventilator. The intratracheal peak pressures at ventilation causing inhibition of phrenic nerve activity decreased with increasing ventilatory frequencies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101384 TI - Fresh gas flow in coaxial Mapleson A and D circuits during spontaneous breathing. AB - In a lung model simulating spontaneously breathing halothane anaesthesia, the rebreathing characteristics of the coaxial Mapleson A (Lack circuit) and D (Bain circuit) systems were tested. Using decreasing fresh gas flows (VF), the end tidal carbon dioxide fraction (FACO2) was monitored and the point of rebreathing (R.P.) detected. The effects of changes in minute volume (VE), dead-space to tidal volume ratio (VD/VT) and carbon dioxide elimination (VCO2) were studied. The effect of increased tidal volumes (VT) on FACO2 was investigated for some different fresh gas flows (VF). The VF/VE ratio for R.P. in the Bain circuit was approximately 2 and in the Lack circuit 0.88. In both circuits an increase in VE and a decrease in the VD/VT ratio resulted in higher demands on VF if rebreathing was to be avoided. The latter effect was much more pronounced in the Lack circuit. In neither system did any changes in VCO2 affect the rebreathing characteristics. The conclusion was drawn that the Lack system is a much better choice concerning the fresh gas flows for anaesthesia with spontaneous breathing than the Bain system. It was also concluded that the fresh gas flows recommended by Humphrey for the Lack system (i.e. 51 ml X min-1 X kg b.w.-1) and by the manufacturers for the Bain system (i.e. 100 ml X min-1 X kg b.w.-1) are inadequate and should be increased if a considerable degree of rebreathing is to be avoided. PMID- 3101385 TI - CBF and CMRO2 during craniotomy for small supratentorial cerebral tumours in enflurane anaesthesia. A dose-response study. AB - In 14 patients with supratentorial cerebral tumours with midline shift less than or equal to 10 mm, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice on the contralateral side of the craniotomy, using a modification of the Kety & Schmidt method. For induction of anaesthesia, thiopental, fentanyl and pancuronium were used. The anaesthesia was maintained with enflurane 1% in nitrous oxide 67%. Moderate hypocapnia to a level averaging 4.3 kPa was achieved. The patients were divided into two groups. In Group 1 (n = 7), 1% enflurane was used throughout the anaesthesia, and CBF and CMRO2 measured about 70 min after induction averaged 30.1 ml 100 g-1 min-1 and 1.98 ml O2 100 g 1 min-1, respectively. During the second CBF study 1 h later, CBF and CMRO2 were unchanged (P greater than 0.05). In Group 2 (n = 7), the inspiratory enflurane concentration was increased from 1 to 2% after the first CBF measurement. In this group a significant decrease in CMRO2 was observed, while CBF was unchanged. In six patients EEG was recorded simultaneously with the CBF measurements. In patients subjected to increasing enflurane concentration (Group 2), a suppression in the EEG activity was observed without spike waves. It is concluded that enflurane induces a dose-related decrease in CMRO2 and suppression in the EEG activity, whereas CBF was unchanged. PMID- 3101386 TI - Peroperative buprenorphine: do high dosages shorten analgesia postoperatively? AB - Fifty-two patients undergoing biliary surgery were investigated in a prospective randomized study, in which they received buprenorphine 10, 20, 30, and 40 micrograms X kg-1, respectively, as sole intravenous analgesic as a bolus 15 min before induction of anaesthesia. The anaesthetic was uneventful in all four groups, although when receiving 10 and 20 micrograms X kg-1 almost two-thirds of the patients needed supplemental analgesics during the operation. When receiving buprenorphine in the dosage of 30 and 40 micrograms X kg-1, 50% of the patients requested an analgesic within 5 min of extubation. In contrast, when receiving 10 and 20 micrograms X kg-1 none of the patients requested an analgesic within 1 h of the operation. These findings accord to a certain extent with the presence of a bell-shaped dose-response curve for buprenorphine in humans. PMID- 3101387 TI - Relationship between frequency of ventilation, airways and pulmonary artery pressures, cardiac output and tracheal tube deadspace. AB - Intravascular and airway pressures, cardiac output (CO) and blood gas tensions were measured in five adult patients after hepatobiliary surgery. They were ventilated at frequencies of 15, 100 and 200 breaths min-1 (bpm) with the respiratory fresh gas (RFG) supplied at the proximal and distal end of a Mallinckrodt Hi-Lo tracheal tube. The peak airway pressure (P AW) fell from 1.20 kPa at 15 bpm to 0.6 kPa at 100 bpm, rising again to 1.9 kPa at 200 bpm, and both changes were significant (P less than 0.05). The mean pulmonary artery pressure (PAMP) remained in the range 1.87-2.00 kPa (14-15 mmHg) at 15 and 100 bpm but rose to over 2.67 kPa (20 mmHg) at 200 bpm (P less than 0.05). Cardiac output, heart rate and systemic arterial pressure remained unchanged. A small but significant (P less than 0.05) reduction in PaCO2 occurred when the RFG was moved to the distal end of the tracheal tube. A theoretical analysis predicts that the minimal P AW to maintain CO2 hemostasis will occur between 30 to 100 bpm, which is reflected in the results of the present study. PMID- 3101388 TI - CO2 production after suxamethonium and diazepam. AB - The CO2-production and degree of relaxation after increasing doses of suxamethonium were measured in seven patients undergoing alloplastic surgery of the hip. The study indicates that the CO2-production rises following the injection of increasing doses of suxamethonium. Another group of patients received diazepam 0.1 mg kg-1 before the injection of suxamethonium 1 mg kg-1. CO2-production was significantly reduced compared to CO2 production when suxamethonium was not preceded by diazepam. It is suggested that diazepam in doses larger than 0.1 mg kg-1 might be effective in preventing fasciculations and postoperative muscle pains before the injection of suxamethonium in a dose of 0.5 mg kg-1. PMID- 3101389 TI - Intensive care of the elderly--a retrospective study. AB - Access to intensive care is to a large extent a prerequisite of the treatment of increasingly old patients for more and more complicated diseases. The ultimate outcome of such treatment is little known, however. In this study we have followed up 143 patients (91 males and 52 females), aged 70 years or more, who were treated in the intensive care unit (ICU) of Danderyd Hospital for 48 h or more during the years 1979-1982. As a comparison, another group of 143 patients in all age groups treated in the ICU for 48 h or more were studied during 1 year (1980). The main diagnostic groups were infectious diseases, trauma, acute abdominal diseases, malignancy, cardiovascular diseases, and other diseases. The mean mortality within 12 months at age 70 years and above was 52%, highest for cardiovascular diseases (73%) and malignant diseases (60%). Within this age group, the main part of the occupancy in our ICU was held by patients who died within 18 months (58%). The results show that the ICU-cost per patient per year saved was not much higher for patients in diagnostic groups with higher mortality or longer duration of stay in the ICU than in other groups. Calculations of ICU cost seem to be a relevant parameter for the evaluation of the results of ICU care. Fifty per cent of all patients were able to return home some time after intensive care. The humanitarian end result is thus encouraging, but better criteria for selection of patients are needed. PMID- 3101390 TI - Alfentanil anesthesia in gall bladder surgery. PMID- 3101391 TI - Effect of diphtheria and tetanus toxoids on the growth of, and imprinting developed in, Tetrahymena. AB - The growth of Tetrahymena was influenced by both diphtheria and tetanus toxoids; depression occurred at a high and stimulation at a low concentration. Pretreatment with the stimulating concentration of diphtheria toxoid caused a lasting modification of growth rate and development of imprinting that resulted in an enhanced response of the cell at reexposure to the toxoid. Tetanus toxoid failed to induce either switch over of cell function or imprinting. PMID- 3101392 TI - Antibacterial activity of primycin against multiple strains of gram-positive bacteria. AB - Crystalline primycin was found to be very active in broth dilution assay against Staphylococcus aureus (50 strains), Staphylococcus epidermidis (77 strains), Streptococcus faecalis (76 strains) and one strain of Listeria monocytogenes with minimal inhibitory concentrations (MIC) of 0.12-0.5 microgram/ml. The activity was influenced by the pH of the liquid medium with greater activity (lower MICs) at pH 8 against the majority of strains, than at pH 6 or 7.3. In disc agar diffusion assay Bacillus subtilis ATCC 6633 proved more sensitive than staphylococcus strains. PMID- 3101393 TI - Serologic and protective cross-reactivity of antisera to Pseudomonas aeruginosa extracellular slime glycolipoprotein. AB - Antisera to extracellular slime glycolipoprotein of Pseudomonas aeruginosa of different O serogroups (immunotypes) show cross reactivity in passive haemagglutination (PHA) and agar gel immunoprecipitation test; cross reactivity is more distinct in PHA. Antisera to glycolipoprotein also have marked cross activity in mouse passive protection test against intraperitoneal challenge with 24 P. aeruginosa strains of different O groups including the toxigenic strain PA 103. On the basis of the results, glycolipoprotein producer P. aeruginosa strains may be selected in order to make a preparation for active and passive immunization against pseudomonas infection. PMID- 3101394 TI - Effect of metal ions on the antimicrobial activity of 5-sulphosalicylic acid. AB - Bis-(5-sulphosalicylato)-diaquo chelates of VO(II), Cu(II), Ni(II), Co(II), Fe(II) and Mn(II) exerted antifungal activities. The chelates have been characterised for elemental, thermal and infra-red spectral studies and were found to be more fungicidal than the chelating agent. The antifungal activity was found to be in the order: Cu(II) congruent to Ni(II) greater than Co(II) greater than Fe(II) greater than Mn(II) greater than VO(II). PMID- 3101395 TI - Menopause, developing countries and the 21st century. AB - According to the independent projections of the United Nations Population Division and of the World Bank, the global population (presently: 4.7 billion) will continue to grow until the year 2100 or 2150, when it is expected to stabilize at an approximate level of 11 billion. Ninety-five per cent of this future growth will occur in developing countries, with an increasing number and proportion of women aged 45 and over; their number will exceed 700 million before the turn of the century. The past decade, or two, witnessed a dramatic increase in life expectancy at birth, especially in developing country women, but little, if any, information is available about the menopause in those countries. An urgent task of high priority is therefore to establish on a country-to-country basis the age distribution and sociocultural significance of the menopause and of the prevalence of various menopausal disorders, which to a huge extent will determine the health- and social service needs of individual developing countries. Furthermore, a rapid progress must be made in the diagnosis, prevention and treatment of osteoporosis, atherosclerotic cardiovascular disease, musculoskeletal disorders and senility. It is suggested that the establishment of a Special Programme of Research by the World Health Organization on the problems of aging would significantly accelerate progress in this field. PMID- 3101397 TI - Female urethral diverticulum with calculus. PMID- 3101396 TI - Clinical experience with a low-dose combination of estradiol valerate and levonorgestrel. Double-blind comparative study between SH D 386 F and Cyclabil. Effects on symptoms, lipids and endometrial condition. AB - In a double blind study of the effects of hormone replacement therapy in climacteric women, two different dosages of estradiol--17 beta valerate and levonorgestrel, with the same ratio between the amounts of the two steroids (Cyclabil and the trial preparation having the code number SH D 386 F respectively), were compared. The differences in effects on symptoms, certain humoral parameters including serum lipids, and endometrial histology before and after 12 months of therapy were evaluated. The study population consisted of 120 healthy women in the age range 41-63 years, many of whom had undergone previous estrogen treatment. All had typical climacteric symptoms and were peri- or postmenopausal. There were no significant differences between the two preparations as regards the effects on symptoms--except for episodes of hot flushes and depression (loss of confidence), which were more frequent during treatment with the higher dosage. One of the main objects of the study was to determine whether the lower dosage would be sufficient to prevent the development of endometrial hyperplasia. To this end, endometrial samples were collected before and after 12 months of treatment, using "Mi-markTM" disposable equipment for endometrial cytology/histology. No significant endometrial hyperplasia was found in either of the groups during the period of investigation. The serum lipid pattern was evidently more influenced in the group treated with Cyclabil. The drop-out rate was 20%, most of them being due to side effects of mild to moderate severity such as undesirable withdrawal bleedings or unsatisfactory relief of symptoms, which sometimes resulted in a wish to return to earlier treatment regimens. PMID- 3101398 TI - Effects of meclofenoxate on learning and memory--dependence on the experimental conditions. AB - In experiments on male albino rats, it was found that meclofenoxate at a dose of 100 mg/kg i. p. applied 7 days before and 5 days during shuttle-box training did not influence learning but significantly facilitated retention (retention test was given 7 days after the end of training). With the step-through method for passive avoidance meclofenoxate at the same dose applied for 7 days improved learning and retention. In the staircase maze training with alimentary reinforcement and in the step-down passive avoidance situation, meclofenoxate at a single dose (50 mg/kg i. p.) applied before or immediately after training only tended to facilitate learning and retention, while applied at the same dose twice daily for 5 days, it significantly improved learning and retention. When meclofenoxate at a dose of 50 mg/kg i. p. was administered twice daily for 5 days in parallel with the staircase maze training, learning reached its maximum on the 5th day and remained at this level till the 10th training day even after withdrawal of meclofenoxate. In the control animals the improvement of learning progressively increased till the 10th training day. The present results suggest that the learning- and memory-facilitating effect of meclofenoxate is influenced by the training method, motivation, dose used and treatment duration. PMID- 3101399 TI - Aminergic control of blood flow in rat cerebral cortex: immunohistochemistry and hydrogen clearance study. PMID- 3101400 TI - Immunohistochemical and pharmacological studies on serotonergic nerves and receptors in brain vessels. PMID- 3101401 TI - Specificity of the cerebrovascular regulation in the rabbit caudate nucleus: effects of adenosine. PMID- 3101402 TI - Intracerebral pathways involved in arterial vasospasm following an experimental subarachnoid haemorrhage. AB - Subarachnoid blood does not induce vasospasm by a direct vascular effect, but via a neural and/or neurohumoral mechanism. Neurons in the A1 and A2 nuclei and in the median eminence region connected by fibres running in the central tegmental tract are necessary for the development of vasospasm following a SAH. PMID- 3101403 TI - Potassium and chloride fluxes are involved in volume regulation in mouse pancreatic islet cells. AB - Potassium and chloride transport were measured in beta-cell-rich islets from ob/ob-mice using 36Cl- and 86Rb+ (K+-analogue). Reduction of the osmolarity from the normal 317 mosm l-1 to 180 mosm l-1 reduced the apparent content of K+ and Cl . Hypo-osmolarity had no effect on the ouabain-sensitive portion of the Rb+ influx (Na+/K+ pump), but reduced the ouabain-resistant portion of the influx. Hypo-osmolarity also strongly increased the Rb+ efflux rate. Both tetracaine (0.5 mM) and glibenclamide (20 microM), which increase the osmotic resistance of pancreatic beta cells, significantly potentiated the reduction in apparent K+ content induced by hypo-osmolarity. This study suggests that the volume regulation in pancreatic beta cells is partly due to K+ and Cl- flux and that glibenclamide and tetracaine increase the osmotic resistance of the beta cells by affecting such ion transport. PMID- 3101404 TI - Simultaneous measurements of gastric motility and acid-bicarbonate secretions in the anaesthetized cat. AB - Chloralosed cats were acutely vagotomized, their splanchnic nerves cut and the adrenal glands ligated. The gastric lumen was perfused with isotonic NaCl and gastric motility was monitored as changes in hydrostatic pressure within the perfusion circuit. Gastric secretion of H+ and HCO3- were calculated from continuous measurements of pH and PCO2. Methodological tests ex vivo showed good accuracy of the estimations. Recovery of H+ after HCl instillation into the stomach in vivo was almost complete, while HCO3- recovery after NaHCO3 instillations was 85-95%. Pentagastrin (10 micrograms kg-1 h-1 i.v.) stimulated gastric contractile activity and increased gastric H+ secretion 30-fold, while HCO3- secretion decreased somewhat. Carbachol (4 micrograms kg-1 h-1) induced gastric contractions and increased H+ secretion by 400% and HCO3- output by 100 130%. Electrical stimulation of the cut vagal nerves (10 Hz for 10 min) induced well known gastric motor responses and increased gastric H+ secretion 20-fold preceded by a transient doubling of HCO3- secretion. Omeprazole, a selective inhibitor of gastric H+ secretion, decreased the vagally induced H+ secretion, while recorded gastric HCO3- secretion was clearly enhanced. In conclusion, the technique permits simultaneous recordings of rapid alterations of gastric motility and H+ and HCO3- secretions. However, HCO3- secretion was modestly underestimated, probably due to mucosal CO2 absorption. PMID- 3101405 TI - The effect of lithium on platelet count. AB - The effect of lithium on platelet count was studied by examining 12 patients treated with lithium carbonate without any additional medication, 13 patients treated with lithium carbonate with additional psychotropic medication, 25 patients with major affective disorder prior to any treatment, 25 patients with panic disorder prior to any treatment and 25 healthy controls. The platelet counts were increased in the group of subjects treated with lithium carbonate without any additional psychotropic medication. The increase was not clinically significant. PMID- 3101406 TI - Effects of a high jugular fossa and jugular bulb diverticulum on the inner ear. A clinical and radiologic investigation. AB - From a series of patients undergoing routine radiographic examination, 112 temporal bones with a high jugular fossa were selected. Among these, 43 jugular bulb diverticula were found. The structures affected by a high fossa or diverticulum were recorded and correlated to the clinical symptoms of the patient. The vestibule was suspected to be affected in five patients. Two of these patients had tinnitus and vertigo, and three had hearing loss. In one of the latter the hearing loss was most marked in the supine position. The cochlea was close to the fossa in three patients, all of whom had tinnitus. Four patients had a defect of the posterior semicircular canal. One of them lost his hearing after a severe fit of coughing, became unsteady and showed signs of a fistula. The internal acoustic meatus and the mastoid portion of the facial canal were affected in two and four patients, respectively, who had no recorded symptoms. Twelve of 34 patients with Meniere's disease and a high jugular fossa on the side of the diseased ear had a dehiscence of the vestibular aqueduct caused by the fossa or diverticulum, compared with nine of 58 patients in the unselected material. For comparison and demonstration of topographic relationships, 58 casts of unselected radiographed temporal bone specimens with high jugular fossae or diverticula were investigated. In patients with a high jugular fossa or jugular bulb diverticulum, tomographic assessment may be of value. PMID- 3101407 TI - Enzymic analysis of polysaccharide structure. PMID- 3101408 TI - The domain structure and the function of poly(ADP-ribose) synthetase. AB - Poly(ADP-ribose) synthetase is a chromatin-bound enzyme which synthesizes a protein-bound homopolymer of ADP-ribose utilizing NAD as a substrate. The characteristic nature of this enzyme is that it requires DNA for catalytic activity. The enzyme is rich in malignant tumor cells as well as in normal tissues where cell proliferation is very rapid. The enzyme has been purified to homogeneity from calf thymus, mouse testis and human placenta. The amino acid composition of these enzymes is very similar and a monoclonal antibody as well as antisera against the calf enzyme cross-reacts with mouse, chicken and human enzymes, suggesting that the antigenic structures of poly(ADP-ribose) synthetase are highly conserved in various animal cells. The native enzyme (Mr = 120K) is cleaved by limited proteolytic digestion into three different domains (Mr = 46K, 22K, 54K), the first containing the site for DNA binding, the second containing the site for automodification and the third containing the site for NAD binding. The DNA binding domain (Mr = 46K), like the native enzyme, has the ability to preferentially suppress nick induced random transcription initiation in a HeLa cell lysate, resulting in the production of run-off RNA initiated from the correct late promoter site on truncated DNA of adenovirus 2. The native enzyme poly(ADP-ribosyl)ates RNA polymerase and some other nuclear enzymes. These results, taken together, indicate that poly(ADP-ribose) synthetase plays a critical role in regulating gene expression in various eukaryotic cells. PMID- 3101409 TI - Kininogen by the SRI method in human serum during an acute phase inflammatory reaction. PMID- 3101410 TI - Kininogen as a pregnancy-associated plasma protein. PMID- 3101411 TI - Purification of inactive kallikrein from rat urine. AB - An inactive kallikrein was purified from rat urine, and some of the properties of this enzyme were examined, in comparison with those of rat urinary kallikrein (RUK). The purified inactive kallikrein reacted with the antiserum against RUK and migrated slightly more slowly than RUK, on the immunoelectrophoresis. The molecular weights of the inactive kallikrein and RUK were estimated to be 44,000 and 38,000 by gel filtration, respectively. These results indicate that the rat urinary inactive kallikrein is immunologically identical with RUK, but this inactive enzyme has biochemical properties different from those of RUK, with respect to molecular weight and electrophoretical mobility. PMID- 3101412 TI - Studies on carbohydrate structure and immunological properties of human urinary kallikreins. AB - Some studies on carbohydrates structure and immunological properties of human urinary kallikreins purified from the human urine of healthy men (HUK) were investigated. A general technique for fractionating asparagine-linked oligosaccharides of HUK was applied. This involves serial chromatographies on concanavalin A-Sepharose 4B and other lectins bound Agarose. Asparagine-linked main oligosaccharides of both active and inactive types of HUK were mixture of tri- or tetra-antennary complex oligosaccharide having GlcNAC beta 1-4Man beta residue (bisecting GlcNAc) (type I-2), bi-antennary complex oligosaccharide having core Fuc alpha 1-6GlcNAc residue (type III-3), tri- or tetra-antennary complex oligosaccharides having Gal beta 1-4GlcNAc beta 1-4 (Gal beta 1-4GlcNAc beta 1-2)Man alpha-residue (type I-1-A-a) etc. Besides these structural studies, the method to probe the heterogeneous profiles of HUK due to the different structures of carbohydrate chains bound, was devised without the complete purification of urinary kallikrein even with individual subject of not only active but also inactive forms of the kallikrein. PMID- 3101413 TI - Characterization of kininogen deficiency of Brown Norway rat mutant Katholiek strain. AB - A deficiency in the plasma kallikrein-kinin system of Brown Norway rat mutant Katholiek strain (B/N-Ka), first reported by Damas et al. was further characterized. The prolonged activated partial thromboplastin time (APTT) of B/N Ka rat plasma was corrected by an addition of rat HMW-kininogen, indicating B/N Ka rat is deficient in HMW kininogen. The study of kinin-release of plasmas of the three strains of rat (B/N-Ka, B/N Ki and SD) by several kininogenases expressed that B/N-Ka rat is deficient in LMW kininogen, in addition to HMW kininogen deficiency. The plasmas of the three strains of rat were gel-filtered through Sephacryl S-200 gel and profiles of kinin-release of the fractions were examined by several kininogenases. The result demonstrated that normal rat plasma contains three kinds of kininogen (HMW and LMW kininogens, and T-kininogen), and B/N-Ka plasma contains only T-kininogen. B/N-Ka rat plasma demonstrated T kininogen antigen but no HMW kininogen by the study of immunodiffusion using their antisera raised in rabbits. PMID- 3101414 TI - Generation of immunoreactive neurotensin(s) and enkephalin(s) by pepsin-treatment of plasma. AB - Treatment of mammalian plasmas with pepsin yielded extraordinary quantities of immunoreactive neurotensin (iNT) and methionine5-enkephalin (iENK). The concentrations measured after pepsin-treatment (iNT, 1-5 microM and iENK, 0.1-0.5 microM) were 1-100 thousand times the normal circulating levels of these peptides. The reactions were shown to be time, temperature and pH dependent and to involve the action of pepsin on albumin-like proteins (Mr, ca, 65,000). Pepsin generated iNT from rat plasma differed from NT since it reacted only with C terminal directed antisera and eluted earlier than NT during HPLC on mu-Bondapak C-18. Partially purified iNT was active in two bioassays for NT, one which senses changes in vascular permeability to protein after intradermal injection into rats and another which measures release of histamine from isolated rat mast cells. Other biologic activities generated by pepsin-treating plasma included effects on systemic blood pressure in rats and on the contractility of the isolated guinea pig ileum. Some of these, however, were attributable to the formation of angiotensin- and bradykinin-related peptides. Pepsin-generated iENK gave three major peaks during HPLC, one of which (ca, 25%) co-eluted with oxidized ENK and also registered in a radioreceptor assay for opiate-related substances. In addition, this material produced ENK-like effects on the isolated guinea pig ileum and on vascular permeability in rat skin. The precursor-like protein(s) for iENK were distinguished from adrenal proenkephalins since it did not liberate iENK upon digestion with trypsin and carboxypeptidase B. Since pepsin can mimic renin these results suggest the existence of systems in blood (analogous to the renin/angiotensin system) for the generation of biologically active NT- and ENK related peptides and they also raise the question as to whether other neuropeptides might be found circulating in precursor form(s). PMID- 3101415 TI - Increase in factor VIII clotting activity in the perfusate of isolated dog hind leg and heart by components of kallikrein-kinin system. AB - Transient increase in Factor VIII clotting (F.VIIIc) activity was observed by infusion of kallikrein or bradykinin (BK) to the isolated dog leg or heart preparation which was perfused with physiological solution, but the increase in Factor IX activity was not observed, suggesting that the increase in F.VIIIc activity was not due to contaminated plasma components of the perfusate. The increase coincided with the increase in prostacyclin (PGI2) which was determined by immunoassay of 6-keto-PGF1 alpha and by platelet aggregation inhibiting activity. Although increase in PGI2 by BK was inhibited by the pretreatment of the preparations with indomethacin or tranylcypromine, the increase in F.VIIIc activity was not inhibited, suggesting that the increase in F.VIIIc activity was not mediated by PGI2. PMID- 3101416 TI - The molecular biology of amino-acid transport in bacteria. PMID- 3101417 TI - Hormonal control of renal medullary functions. PMID- 3101418 TI - Multiple hormonal control of the thick ascending limb functions. PMID- 3101419 TI - Pharmacology of loop diuretics: state of the art. PMID- 3101420 TI - Acute renal failure: a disease of the elderly? PMID- 3101421 TI - Glomerular cells in vitro. PMID- 3101422 TI - From the renin gene to renin inhibitors. PMID- 3101423 TI - Endourology. PMID- 3101424 TI - Treatment of idiopathic membranous nephropathy. PMID- 3101425 TI - Drug-induced autoimmune disease. PMID- 3101427 TI - Berger's disease: recent advances in immunology and genetics. PMID- 3101426 TI - Physiopathologic aspects of Tamm-Horsfall protein: a phylogenetically conserved marker of the thick ascending limb of Henle's loop. PMID- 3101428 TI - Autoimmunity and glomerulonephritis. PMID- 3101429 TI - Kidney transplantation in children: results of 383 grafts performed at Enfants Malades Hospital from 1973 to 1984. PMID- 3101430 TI - Cyclosporine in pediatric kidney transplantation. AB - The immunosuppressive treatment with cyclosporin A plus low-dose prednisolone in 33 children after kidney transplantation was compared with conventional treatment with azathioprine plus regular prednisolone dosage in 34 children. The results showed the following: Graft survival in the CyA group is significantly better than in the conventional group (97% vs. 68% at one year). Patient survival is the same in both groups (97% vs. 94%). Kidney function six weeks and one year after successful renal transplantation is significantly lower in the CyA group than in the conventional group. The major nephrotoxic effect of CyA seems to be related to the first period after kidney transplantation, since later the decline in renal function is the same in both treatment groups. Other side effects of CyA are not severe and are well manageable. A major benefit of CyA treatment is the growth after transplantation, which is significantly better than in the conventional group. Almost all transplanted children show normal or even catch-up growth rates. PMID- 3101431 TI - Cardiovascular stability on hemodialysis. PMID- 3101432 TI - Erythropoietin: structure, function, origin. PMID- 3101433 TI - Do glucocorticosteroids play a role in the regulation of blood pressure? A study performed with a glucocorticosteroid antagonist. PMID- 3101434 TI - Thick ascending limb--anatomy and function: role in urine concentrating mechanisms. PMID- 3101435 TI - Intensive monitoring in infants and children. PMID- 3101436 TI - Role of intensive monitoring in classification. PMID- 3101437 TI - Epilepsy presurgical evaluation in the era of intensive neurodiagnostic monitoring. PMID- 3101438 TI - Closed-circuit television videotaping and electroencephalography biotelemetry (video/EEG) in primary generalized epilepsies. PMID- 3101439 TI - Impact of alcoholism treatment on total health care costs: a six-year study. AB - This is a six-year longitudinal study to determine if the treatment of alcoholism as a primary diagnosis results in a reduction of total health care cost and/or utilization for the alcoholic as well as other nonalcoholic family members. All health care costs and utilization were tracked for a group of 90 families, representing 245 individuals, enrolled with Blue Cross/Blue Shield through the Health Benefits Division, California Public Employees Retirement System. At least one member in each family received treatment under a specific diagnosis of alcoholism from July 1, 1974 to December 1, 1975. All health care utilization and costs were obtained for a 12-month period before initial treatment for alcoholism and up to July 1, 1979. In addition, a matched group of 83 comparison families with no alcoholic members and covering 291 persons was selected to reflect family composition, age, and sex. Total health care data were obtained over the same time period for these families. The results indicated that utilization and costs of all forms of inpatient care for both nonalcoholic family members as well as alcoholic family members dropped after alcoholism treatment began and ultimately reached a level similar to the matched comparison group. On the average, outpatient care also decreased in terms of frequency and costs for all members of the alcoholic's family; and in similar fashion converged in the fourth follow-up period to the matched comparison families. Total health care costs per family member decreased substantially over time following initiation of treatment of the alcoholic family member. The findings support the contention that the direct treatment of alcoholism can yield significant reductions in total health care costs and utilization not only for the alcoholic but his/her family members as well. PMID- 3101440 TI - Role of platelet membrane phospholipids in signal transduction. PMID- 3101441 TI - The role of phosphorylation/dephosphorylation reactions in the function of blood platelets. PMID- 3101442 TI - Mode of action of currently used antiplatelet drugs. PMID- 3101443 TI - Modifications of platelet functional and biochemical parameters in human type IIa hypercholesterolemia. PMID- 3101444 TI - Comparison of the effects of oral and intravenous aspirin administration on platelet and peripheral vascular cyclo-oxygenase activity: studies in rats and in man. PMID- 3101445 TI - Platelet activation induced by FMLP-stimulated neutrophils. PMID- 3101446 TI - [Spontaneous rupture of renal leiomyosarcoma: report of a case]. AB - A case of renal leiomyosarcoma ruptured spontaneously is reported. A 36-year-old man was admitted to our clinic with the complaint of right flank pain. The urographic examination, including an excretory urography, renal CT-scan, renal angiography, and ultrasonography revealed a renal tumor with spontaneous rupture on the right side. A nephrectomy through the lumbal flank incision on the right side was performed on February 28, 1984, and histopathological diagnosis was renal leiomyosarcoma. Five courses of adjuvant chemotherapy, VCR, ADM and CPM, combined with maintenance immunochemotherapy using Tegafur and Krestin and with radiotherapy (3,000 rad) were performed post-operatively. The patient was followed for 18 months after operation as an outpatient with no evidence of local recurrence and metastasis. The 40 reported cases including our case with leiomyosarcoma in Japan is reviewed and some characteristics of this entry are discussed. PMID- 3101447 TI - [Clinical trial of HAPA-B in complicated urinary tract infections]. AB - HAPA-B was administered intramuscularly to 20 patients with complicated urinary tract infections to evaluate its clinical effects and safety in conformity with the estimations of efficacy of antimicrobial agents standardized by the UTI Committee. The overall clinical efficacy was excellent in 5 patients, moderate in 8 patients and poor in 7 patients. The effectiveness rate was 65.0%. Overall clinical efficacy as classified by type of infection was 66.7% in 12 patients with a single infection, and 62.5% in 8 patients with mixed infection. Bacteriological studies showed that 29 of the 34 strains isolated from the urine of the 20 patients were completely eradicated, and that the bacteriological response was 85.3%. The following side effects were detected in both blood chemistry checks and clinical symptoms. Peripheral blood examinations showed an increase in eosinophil level in one patient. Kidney function tests revealed a slight elevation of s-creatinine in this patient, too. In another patient, eruptions developed on his body on the 2nd day, but it was not necessary to discontinue the administration of HAPA-B. PMID- 3101448 TI - [A clinical evaluation of MK-0787/MK-0791 for long-term administration in urological infections]. AB - MK-0787 (Imipenem)/MK-0791 (Cilastatin sodium), a new compound of Thienamycin, was administered in treatment of 35 patients (36 cases) with chronic complicated UTI or for prevention of serious infections with much complicated factors. The patients were principally treated at a daily dose of 1 g for over 10 days. The efficacy rate of 26 patients who were evaluable in the early phase (4-7 days) was 88.5%, while it became up to 92.3% in the final phase judgment. As for clinical usefulness, the result was obtained to be as high as that of the clinical efficacy. In bacteriological study, 35 strains were clinically isolated including 7 strains of P. aeruginosa from UTI. All the strains disappeared with an eradication rate of 100% after treatment. Strains appearing after Imipenem/Cilastatin sodium treatment mainly consisted of fungi. Usefulness judgements tended to be greater in the final phase than in the early phase. As for side effects, vomiting was recorded in one case, in which the administration was discontinued. In laboratory findings there were 3 cases with elevated GPT, 2 cases with elevated GOT, one case with elevated gamma-GTP, one with thrombocytopenia, and one with eosinophilia each, but these abnormal values were slight and transient. In summary our clinical study showed that Imipenem/Cilastatin sodium was a very effective antibiotic in treatment on moderate or serious UTI or preventive use for infections in compromised hosts. Considering the features of this agent, it might be more effective and useful for clinical use in treatment on polymicrobial infections including stubborn organisms than any other antimicrobial compounds. Furthermore, it was safe and well tolerable in a long term treatment. PMID- 3101449 TI - Translumbar inferior vena cava Hickman catheter placement for total parenteral nutrition. PMID- 3101450 TI - Chemonucleation and changes observed on lumbar MR scan: preliminary report. AB - This study examines the relation between the postchemonucleation clinical outcome and changes observed on the lumbar MR scan. Eight of 12 chemonucleated disks showed clinical improvement at the last follow-up, while the other four showed no improvement. In the cases that showed improvement there was a decrease in one or both dimensions of the defect in the thecal sac. Seven of eight showed an increase in the peridisk signal. Where there was no clinical improvement there were fewer decreases in the size of the defect, and three of four showed no increase in the peridisk signal. PMID- 3101451 TI - Conventional and CT metrizamide myelography in Arnold-Chiari I malformation and syringomyelia. AB - Four normal controls and 26 cases of Arnold-Chiari I malformations and/or syringomyelia were reviewed. The pathologic cases included five isolated Arnold Chiari I malformations, nine communicating syringomyelia, five idiopathic syringomyelia, four posttraumatic syringomyelia, one syringomyelia with hemangioblastoma, and two postshunt syringomyelia. The objectives of this study were to compare the accuracy of conventional metrizamide myelography with CT metrizamide myelography and to study indirectly the hydrodynamics of CSF flow in syringomyelia by comparing the sequential enhancement patterns of the spinal cords and cord cavities in the different groups of patients. Twenty-five patients underwent conventional metrizamide myelography immediately before CT metrizamide myelography, and one patient underwent CT metrizamide myelography only. Scans were obtained 1-2 hr, 4-8 hr, and 12-24 hr after injection of metrizamide, but not all patients were scanned during all three intervals. CT metrizamide myelography was found to be more sensitive than conventional metrizamide myelography in the diagnosis of both Arnold-Chiari I malformation and syringomyelia. Performing just an immediate and a delayed scan was found to be more cost-effective than doing all three scans. Contrary to previous reports, it was found that delayed (12-24 hr) scans demonstrated more syrinx cavities than intermediate ones. In studying the sequential enhancement patterns of the spinal cords and cord cavities, some interesting trends were observed that tend to support the theories of Aboulker and of Ball and Dayan of transneural passage of CSF into cord cavities in syringomyelia. PMID- 3101452 TI - Hyperprolactinemia: an unusual manifestation of suprasellar cystic lesions. AB - Two patients with suprasellar cysts and hyperprolactinemia are described. These lesions were diagnosed by CT metrizamide cisternography. Suprasellar cysts are a rare cause of pathologic hyperprolactinemia, which most commonly results from pituitary adenomas. Tissue diagnosis revealed suprasellar arachnoid cysts in the first patient and Rathke's cleft cyst in the second. The differential diagnosis of suprasellar cysts is presented, and distinguishing radiographic characteristics are discussed. PMID- 3101453 TI - Angiographic features of gliosarcoma. AB - Gliosarcoma is a brain neoplasm that is being recognized with increasing frequency. We discuss the radiographic findings in 14 pathologically proven cases. At angiography in nine cases, four showed mixed dural and pial vascular supply to the lesion. Early cortical venous drainage, irregular tumor vessels, and a prominent vascular stain with well-defined tumor margins were seen in the majority of cases. CT showed an irregular enhancing rim surrounding a necrotic center in 14 cases. Most lesions were peripherally located and invaded dura. PMID- 3101454 TI - Brain death: use of dynamic CT and intravenous digital subtraction angiography. PMID- 3101455 TI - "Benign" metastasizing meningiomas. AB - Less than one in 1000 meningiomas metastasizes. Although the angioblastic and hemangiopericytic tumors are believed by some authors to metastasize with a greater frequency than the other histologic forms of meningioma, most investigators believe that neither the histologic pattern, local aggressiveness, size, nor location of the tumor can be used accurately to predict which tumors will metastasize. Three new cases are presented, bringing the total reported number of metastasizing meningiomas to 113. If the angioblastic meningiomas and hemangiopericytomas are eliminated from this group, 69 reported cases of "benign" metastasizing meningioma remain. PMID- 3101456 TI - Modified CT techniques in the evaluation of temporal lobe epilepsy prior to lobectomy. AB - The outcome of temporal lobectomy performed for seizure control is improved by preoperative identification of structural lesions. We used cranial CT, modified to improve visualization of mesial temporal structures, as a means of preoperative evaluation in 48 patients with partial complex seizures. The axial views, parallel to the temporal fossa, improved visualization of five lesions, including two that were not diagnosed by routine cranial CT. In 12 patients, intrathecal metrizamide was used; the rest received intravenous contrast. These modified techniques could not reliably predict mesial temporal herniation; however, modified axial CT with intravenous contrast is recommended for evaluation of suspected temporal lobe pathology. PMID- 3101457 TI - The optic neurogram: evaluation of CSF "block" caused by compressive lesions at the optic canal. AB - Patients with progressive blindness resulting from bony proliferative diseases such as osteopetrosis may benefit from optic canal decompression. A radiologic technique is described whereby the practicality of surgical optic canal widening is evaluated preoperatively using the intrathecal water-soluble contrast agent lopamidol. Conceptually, if a patient who is losing vision demonstrates a block on the optic neurogram, then likely there is still sufficient neural tissue within the optic canal and sheath to cause obstruction, and therefore decompression may be indicated. However, if preoperatively there is no block to lopamidol, then surgical intervention is not indicated, as the nerve has already undergone severe atrophy to the point of "autodecompression." Cases of differing etiologies, with and without blocks, illustrate the utility of the method and point out the importance of early surgical management to prevent irreversible damage to the optic nerve. PMID- 3101458 TI - Head-hanging CT: an alternative method for evaluating traumatic CSF rhinorrhea. PMID- 3101459 TI - Intense brain cortical enhancement on CT in laminar necrosis verified by biopsy. PMID- 3101460 TI - Gas CT cisternography of trigeminal neuralgia caused by AVM of the cerebellopontine angle. PMID- 3101461 TI - Unilateral calcification and contrast enhancement of the basal ganglia in a child with AIDS encephalopathy. PMID- 3101463 TI - Acute subdural hematoma mimicking epidural hematoma on CT. PMID- 3101462 TI - Actinomycotic granuloma of the trigeminal ganglion. PMID- 3101464 TI - Use of a cervical spine collar during MR studies. PMID- 3101465 TI - MR in spinal tuberculous abscess. PMID- 3101466 TI - Air in the cavernous sinus: a new sign of septic cavernous sinus thrombosis. PMID- 3101467 TI - The ascending pharyngeal artery: a collateral pathway in complete occlusion of the internal carotid artery. PMID- 3101468 TI - MR imaging of moyamoya in neurofibromatosis. PMID- 3101469 TI - Evaluation of traumatic atlantooccipital dislocations. AB - The diagnosis of traumatic atlantooccipital dislocation (AOD) from the cross table lateral radiograph is difficult because of problems in demonstrating the complex anatomy of this area and the intricate radiographic methods used to diagnose AOD. Although CT or polytomography seem to be the most accurate diagnostic methods, it is often the lateral radiograph from which the diagnosis and further decisions are made. To determine both the best radiographic method for diagnosing AOD from the lateral radiograph and the role of CT and tomography in the diagnosis of AOD, the literature was reviewed concerning how the diagnosis of AOD has been obtained. In addition, the Wholey dens-basion line, the Powers ratio, the Dublin method of diagnosing AOD, and measurement of the atlantooccipital joint width were applied to 12 cases of traumatic AOD; and the Wholey dens-basion line and the Powers ratio were determined in 100 normal adults and 50 normal children. An alternative plain radiographic method for diagnosing AOD was developed, called the X-line method. This was the most accurate of the methods tested, correctly diagnosing AOD in 75% of cases. The Wholey dens-basion line and direct measurement of the atlantooccipital joint width were each correct in 50% of cases, the Powers ratio in 33% of cases, and the Dublin method in only 25% of cases. Ultimately, either CT or polytomography should provide the definitive diagnosis. In this regard high-resolution CT with reformatted coronal and sagittal images generated from 2-mm thin axial slices appeared to have the most promise as the first study of choice. PMID- 3101470 TI - MR imaging of acute spinal cord trauma. AB - The thoracic spinal cords of five mongrel dogs were imaged with a 1.5 T MR scanner before and after trauma induced by a well-established method of spinal cord impaction that produces central cord hemorrhagic necrosis. The anesthetized dogs were studied acutely with a 5-in. circular surface coil, 12-cm field of view, sagittal and axial partial-saturation (TR = 600, TE = 25 msec) and spin echo (TR = 2000, TE = 25-100 msec) techniques. One normal dog was used as a control. The cords were surgically removed and histologically examined. Direct correlation of the pathologic findings and imaging data showed that at the level of trauma there was obliteration of epidural fat and CSF spaces secondary to central cord hemorrhage and edema. The traumatized cords expanded to fill the bony canal, and there was loss of visualization of the internal anatomy of the cord (gray- and white-matter structures). We conclude that MR can accurately identify cord hemorrhage and edema within a few hours of spinal trauma. PMID- 3101472 TI - MR imaging of the mesencephalic tectum: normal and pathologic variations. AB - Variations of the quadrigeminal plate (mesencephalic tectum) were determined on midline sagittal MR images of the brain in 93 patients without known mesencephalic abnormalities and in 10 patients with known aqueductal stenosis or obstruction. Measurements of the thicknesses of the superior and inferior colliculi and the length of the tectum were made on the midline sagittal section. Images were obtained with a 0.5 T system with spin-echo pulse sequences using a TE of 30 or 40 msec with a TR of 500-1500 msec. The average thickness of the superior and inferior colliculi was about 5 mm, but the range was from 2-7 mm on the midline sagittal section. Abnormally thin colliculi appeared to have no clinical significance while abnormal thickness was observed in patients with neoplastic disease, sarcoidosis, and mesencephalic "beaking." While most neoplasms have abnormal signal intensity on T2-weighted images, small lesions may be difficult to perceive on transaxial images due to volume averaging or noncontiguous sections. Measurements of the tectum, on the commonly obtained midline sagittal section, may be useful for patients with small infiltrative lesions. PMID- 3101471 TI - MR of CSF flow phenomenon mimicking basilar artery aneurysm. AB - CSF motion from transmitted vascular pulsations can result in focal areas of CSF hypointensity on MR images because of signal mismapping from phase shift. When this CSF flow void occurs adjacent to the basilar artery in the prepontine cistern, it may be mistaken for a basilar artery aneurysm on proton-density and T2-weighted spin-echo images. Head MR scans of 50 consecutive patients referred for various indications were reviewed, and this phenomenon was noted in the prepontine cistern in 38 patients. Fifteen of these images had an appearance mimicking an aneurysm. When doubt exists, dynamic high-resolution CT scans should be sufficient for clarification. PMID- 3101473 TI - MR of Leigh's disease (subacute necrotizing encephalomyelopathy). AB - MR images of three patients with Leigh's disease (subacute necrotizing encephalomyelopathy) were compared with CT findings. In all patients typical lesions in the basal ganglia were identified with both MR and CT. In two patients MR permitted identification of additional lesions not detected with CT. In one patient progression of MR abnormalities over a 4-month period correlated well with clinical deterioration in neurologic status. T2-weighted images with a repetition time (TR) greater than 1950 msec and an echo time (TE) greater than or equal to 60 msec or inversion-recovery images with a 50-msec TE, 1213-msec inversion time, and 3000-msec TR were advantageous in identifying multiple necrotic lesions in the brainstem, deep gray matter, periventricular white matter, and cerebral cortex. In this series MR was more sensitive in detecting and localizing multifocal necrotic lesions of Leigh's disease than CT was, and thus may be a useful diagnostic tool for patients with the appropriate clinical and laboratory abnormalities. PMID- 3101475 TI - Optimizing MR imaging for detecting small tumors in the cerebellopontine angle and internal auditory canal. AB - Relative resolving power was used to determine the optimal MR imaging pulse sequence for detecting small tumors of the internal auditory canal and the cerebellopontine angle. Resolving power takes into consideration these important image characteristics: signal-to-noise ratio, contrast, and spatial resolution. The study was performed on a 1.5-T magnet using a 256 X 256 matrix and a 3-mm slice thickness. The TR ranged from 400-2000 msec; the number of excitations was either two or six; and the pixel size was 0.94, 0.78, or 0.63 mm. Theoretical calculations of relative resolving power were compared with the relative resolving power of 45 control patients and 15 patients with small tumors of the cerebellopontine angle or internal auditory canal. A TR of 800 msec was optimal from theoretical calculations and proved optimal in control and tumor patients. Scans obtained with TR = 2000 msec, TE = 80 msec were inferior to short TR scans; such scans could fail to detect intracanalicular tumors. The relative resolving power in patients exceeded theoretical calculations because of greater than expected image contrast caused by low CSF signal intensity secondary to CSF pulsation. PMID- 3101474 TI - Serial MR imaging in neonatal cerebral injury. AB - The results of serial MR imaging of the brain in 32 patients with neonatal cerebral injury who had two or more examinations are reviewed. By comparison with normal age-matched controls, delayed or deficient myelination was identified in eight patients on follow-up examination. Developmental delay was present in all of these patients. In three patients delayed myelination was identified at the first study and was normal at follow-up. These patients improved clinically. The most severe delays or deficits in myelination and the most severe handicaps were present in patients with subcortical and periventricular leukomalacia. Ventricular size was readily assessed. Development of porencephalic cysts at sites of previous hemorrhage and infarction was recognized. The lack of ionizing radiation is of particular importance in follow-up MR of children, and an increasing role for this technique in pediatric developmental neurology appears likely. PMID- 3101476 TI - Dynamic variations in resistance of coronary arterial narrowings in angina pectoris at rest. AB - The coronary hemodynamic events in 4 patients with frequent episodes of spontaneous rest angina were investigated. The basal coronary transstenotic pressure gradients showed more severe stenosis than that seen on coronary arteriography, suggesting that angiography in this setting may underestimate the true extent of coronary atherosclerosis. Episodes of angina were triggered by marked, sudden increases in the transstenotic coronary pressure gradient and a decrease in coronary blood flow without alterations in systemic arterial pressure or heart rate. These changes in coronary hemodynamics were promptly reversed by the intracoronary administration of nitroglycerin. No such spontaneous variations in transstenotic coronary pressure gradients were observed in 37 patients with a history of classic exertional angina but no rest angina. These unique data represent direct hemodynamic evidence that an increase in resistance at the site of a coronary stenosis, most likely the result of an increase in arterial tone, can be a cause of transient myocardial ischemia in patients with angina at rest. PMID- 3101477 TI - A comparative evaluation of hemodynamic and neurohumoral effects of nitroglycerin and nifedipine in congestive heart failure. AB - Nitroglycerin and nifedipine have been suggested as useful agents in the therapy of congestive heart failure. Because of the rapid action and feasability for sublingual administration of both drugs, their comparative hemodynamic and neurohumoral effects were studied in 12 patients with congestive heart failure. After sublingual nitroglycerin, there was a significant decrease in mean arterial pressure (96 +/- 17 to 90 +/- 15 mm Hg, p less than 0.01), left ventricular (LV) filling pressure (30 +/- 12 to 22 +/- 10 mm Hg, p less than 0.01), right atrial pressure (15 +/- 6 to 10 +/- 5 mm Hg, p less than 0.01) and systemic vascular resistance (21.5 +/- 7.7 to 19.3 +/- 6.2 units, p less than 0.05) and an increase in cardiac index (2.2 +/- 0.6 to 2.4 +/- 0.7 liters/min/m2, p less than 0.05) and LV stroke work index (20.4 +/- 7.0 to 24.5 +/- 8.6 gm-m/m2, p less than 0.01). After sublingual nifedipine, there was also a significant decrease in mean arterial pressure (96 +/- 16 to 89 +/- 14 mm Hg, p less than 0.01) and systemic vascular resistance (22.1 +/- 7.1 to 18.0 +/- 6.1 units, p less than 0.01) and an increase in cardiac index (2.1 +/- 0.6 to 2.4 +/- 0.6 liters/min/m2, p less than 0.01); in contrast to nitroglycerin, this was unaccompanied by significant changes in right- or left-sided filling pressures or LV stroke work index.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101478 TI - Cigarette smoking-induced coronary vasoconstriction in atherosclerotic coronary artery disease and prevention by calcium antagonists and nitroglycerin. AB - In patients with coronary artery disease, cigarette smoking increases myocardial oxygen demand but may cause an inappropriate alpha-adrenergically mediated fall in myocardial oxygen supply. This study was performed to determine if smoking induced coronary vasoconstriction is prevented by nitroglycerin, verapamil or nifedipine treatment. In 25 smokers with coronary artery disease (20 men, 5 women, aged 32 to 65 years), heart rate-systolic arterial pressure double product and coronary sinus blood flow (thermodilution) were measured before and during smoking both before and 30 to 60 minutes after administration of saline solution (n = 5, control subjects); nifedipine, 10 mg sublingually (n = 6); verapamil, 10 mg intravenously (n = 7); or nitroglycerin, 0.4 mg sublingually (n = 7). During the first smoking period, double product increased, but coronary sinus flow did not change or decreased. During the second smoking period, in the control subjects double product and coronary sinus flow responded in a manner similar to that observed previously. In those given nifedipine, double product did not change, but coronary sinus flow increased (-4 +/- 5% during the first smoking period [before nifedipine] and 17 +/- 12% during the second period [after nifedipine], p less than 0.01). In those given verapamil, double product and coronary sinus flow increased during smoking (-12 +/- 8% during the first smoking period [before verapamil], 10 +/- 9% during the second period [after verapamil], p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101479 TI - Changes of plasma levels of apolipoproteins A-I, A-II, and B and their isoforms in patients with intestinal failure receiving long-term parenteral nutrition. AB - We have studied the plasma lipid and apolipoprotein profiles of 19 patients with intestinal failure who are receiving long-term total parenteral nutrition (TPN). These patients had significantly reduced levels of total and HDL cholesterol and normal levels of triglycerides. Radioimmunoassay determination of apolipoproteins showed a 30% and 50% reduction in apo A-I and A-II levels, respectively. Apolipoprotein B was normal in all but three patients. Isoelectric focusing showed two major isoforms of apo A-I in patients as compared with four isoforms observed in normal subjects and one major isoform of apo A-II compared with multiple isoforms. Recent epidemiologic studies indicate that an increased apo B:apo A-I ratio may be an important factor in atherogenesis. We suggest that patients with small-bowel syndrome who are currently on TPN may be at greater risk for atherosclerosis. Since TPN has restored a reasonably normal life expectancy for these patients, long-term follow-up will likely provide answers. PMID- 3101480 TI - Lactose digestion by yogurt beta-galactosidase: influence of pH and microbial cell integrity. AB - Lactase-deficient subjects more effectively digest lactose in yogurt than lactose in other dairy products, apparently due to yogurt microbial beta-galactosidase (beta-gal) which is active in the GI tract. We evaluated the effects of buffering capacity of yogurt, gastric pH, and microbial cell disruption on beta-gal activity and lactose digestion. Three times more acid was required to acidify yogurt than to acidify milk. Yogurt beta-gal was stable at pH 4.0 but inactivated at lower pH. When yogurt was sonicated to disrupt microbial cell structure, only 20% activity remained after incubation at pH 4.0 for 60 min. In vivo gastric pH remained greater than 2.7 for 3 h after ingestion of yogurt. Acidified milk alone or with disrupted yogurt microorganisms caused twice as much lactose malabsorption as did acidified milk containing intact yogurt microorganisms. The results provide a possible explanation for the survival of beta-gal activity from yogurt in the GI tract. PMID- 3101481 TI - Subnormal concentrations of serum selenium and plasma carnitine in chronically tube-fed patients. AB - Forty-seven tube-fed nursing home patients were investigated with regard to serum or plasma selenium (Se), carnitine, and red blood cell (RBC) glutathione peroxidase (GSH-Px). Thirty-six patients were tube fed with Isocal, and 11 were tube fed with Compleat B, an L-carnitine-containing formula. Eighteen elderly nursing home patients and 10 young adults served as controls. Serum Se and plasma carnitine were lowest (p less than 0.05) in the Isocal patients. In all 36 Isocal subjects, Se was below normal, and in 26% of Isocal patients RBC GSH-Px was also below normal. Free and total carnitine were below normal in most Isocal subjects. All 11 Compleat B patients had subnormal serum Se, but most had normal carnitine concentrations. These data suggest that enteral formulae in nursing homes should contain greater than 100 micrograms Se and on the order of a mmol carnitine/1600 kcal. PMID- 3101482 TI - Screening for marasmus: a discriminant analysis as a guide to choose the anthropometric variables. AB - In a cross-sectional study, children 0-6 yr of age from eight different population groups in Africa and Asia were examined. Clinical assessment defined 8750 children as being well nourished and 194 as having marasmus. Height, weight, arm circumference (AC), and triceps skinfold thickness were measured; the latter two measurements and the clinical assessment were done by the same observer. Based on data from normal children, local growth curves were computed for each group. Each child's growth was expressed in standard deviation scores (SDS) of his own group. On the basis of the results of a discriminant analysis, all variables were ranked by their decreasing power to discriminate between normal and marasmic children. For 83% of the children one measurement (AC/age) is sufficient to classify them definitely; for the others several variables are needed. This strategy yields an overall sensitivity of 80%, a specificity of 97%, and a positive predictive value of 38%. PMID- 3101483 TI - Retinopathy of prematurity. Risk factors in a five-year cohort of critically ill premature neonates. AB - We studied the importance of exposure to an elevated partial pressure of carbon dioxide (PCO2) in the development of scarring retinopathy of prematurity (SROP) in a cohort of 92 neonates with chronic lung disease (greater than or equal to 14 days of respiratory therapy, greater than or equal to 30 days of oxygen therapy, and greater than or equal to 70 days in the hospital), 31 of whom had SROP. This cohort was chosen to avoid confounding prolonged respiratory failure with the presence of SROP and because such a cohort was expected to contain approximately 85% of all patients with SROP. Patients with SROP had a lower PCO2 and spent more time on a respirator at higher respirator pressures during the first 70 days of life. In addition, infants with SROP had a lower mean arterial pressure and had a higher prevalence of seizures (97% vs 43%) and intraventricular hemorrhage (52% vs 26%). We conclude that an elevated PCO2 is not associated with SROP in this group of critically ill premature neonates but that the presence of a seizure disorder or an intraventricular hemorrhage is strongly associated with SROP. PMID- 3101484 TI - Five vs ten days of penicillin V therapy for streptococcal pharyngitis. AB - To determine the effectiveness of a short (five-day) course of penicillin V potassium therapy, 172 patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis were randomly assigned to receive 250 mg of penicillin V potassium three times daily for either five or ten days. The patients in the two treatment groups were comparable with respect to clinical findings, compliance, and serologic response to GABHS. A bacteriologic treatment failure was defined as the presence of the same serotype of GABHS in the follow-up as in the initial throat culture and occurred in 13 (18%) of the 73 patients in the five-day treatment group and in six (6%) of the 99 patients in the ten-day treatment group. These findings support the current recommendation for a full ten days of oral penicillin V therapy for the treatment of GABHS pharyngitis. PMID- 3101486 TI - The best of times--the worst of times. PMID- 3101485 TI - The use of theophylline clearance in pediatric status asthmaticus. II. The choice of appropriate dose for the intravenous theophylline infusion. AB - We developed an individualized approach for determining the intravenous rate of theophylline infusion for the treatment of status asthmaticus in children. The method is based on the individual's theophylline clearance rate as determined at previous admissions. We compared the method with two standard recommended approaches used currently in clinical pediatrics--the American Academy of Pediatrics and the Food and Drug Administration guidelines. PMID- 3101487 TI - Enterolith ileus resulting from small bowel diverticulosis. AB - Small intestine diverticula are infrequent. These acquired pulsion diverticula are postulated to be a result of intestinal dyskinesis. Usually asymptomatic, they can produce a variety of disorders such as malabsorption, hemorrhage, diverticulitis, and perforation. The rarest complication appears to be enterolith formation and obstruction. It is postulated that dyskinesis and stasis leads to bacterial overgrowth causing decomposition of bile salts allowing precipitation and concretion. Presented is an ileal obstruction from a small bowel enterolith. A literature review revealed 25 other cases of obstruction. Most of these cases were treated with simple removal, some with small bowel resection. Results are good and recurrences have not been observed. PMID- 3101489 TI - Endoscopy, obstructive jaundice, and DRGs: the buck stops in the hospital bank account. PMID- 3101488 TI - Escherichia coli peritonitis after left-sided colonoscopy in a patient on continuous ambulatory peritoneal dialysis. AB - A 69-yr-old man on chronic ambulatory peritoneal dialysis presented with Escherichia coli peritonitis 36 h after left-sided colonoscopy. No evidence for colonic perforation was found and the infection cleared with intravenous and intraperitoneal antibiotics. This case supports the need for further studies evaluating the use of prophylactic antibiotics during colonoscopy of chronic ambulatory peritoneal dialysis patients with diverticula. PMID- 3101490 TI - Natural history of acquired immunodeficiency syndrome in hemophilic patients. AB - During the 5-year period from 1981 to 1985, we have observed 8 cases of acquired immunodeficiency syndrome (AIDS) among our 85 patients with hemophilia A. Thus, the prevalence of AIDS with hemophilia A is 9.4% in our patient population. By utilizing stored serum or plasma samples dating back to 1978, antibody against HTLV-III was detected in all 8 cases with AIDS. Based on the time interval from the appearance of antibody to HTLV-III to the diagnosis of AIDS in these patients, the incubation period ranged from 27 months to 60 months, with a median of 36 months. Before the diagnosis of full-blown AIDS, all patients exhibited a variety of prodromal manifestations of non-specific nature, including weight loss, oral candidiasis, unexplained non-productive chronic cough, generalized lymphadenopathy, and thrombocytopenia lasting several months to several years. Serial T-lymphocyte subset studies were available in some patients during the HTLV-III seropositive period and showed progressive lymphopenia, depletion of T4 cells with an average absolute count of 94 +/- 128 per mm3 (mean +/- 1 S.D.), and a markedly reversed T4/T8 ratio of 0.26 +/- 0.19 (mean +/- 1 S.D.). These findings suggest that the incubation period of AIDS is considerably long and that prospective study of serial immunologic markers and HTLV-III markers may be warranted in hemophilic patients at risk. PMID- 3101492 TI - Additional variant of type I von Willebrand disease. AB - We introduce a family with a von Willebrand subgroup that has not been described before. All of the eight subjects examined had normal levels of factor VIII coagulant activity (FVIII:C), a moderate reduction in the level of von Willebrand factor antigen (VWF:Ag), which resulted in a high FVIII:C/VWF:Ag ratio, and normal crossed immunoelectrophoresis, with normal multimeric pattern. The ristocetin cofactor in plasma and platelets was very low. Bleeding time was prolonged in two subjects without clearcut linkage to laboratory findings. In addition, an abnormality of platelet aggregation in response to ADP was observed: a decreased initial response was followed by marked disaggregation. PMID- 3101491 TI - Immunogold staining of microtubules in resting and activated platelets. AB - A circumferential microtubule is known to support the discoid form of resting platelets, but its fate following exposure of the cells to aggregating agents is uncertain. The present study has employed an immunocytochemical approach to follow the fate of the circumferential microtubule in activated platelets. Monoclonal antibodies to tubulin and to vinculin and a polyclonal antibody to actin were incubated with isolated microtubule coils and stained with staphylococcal protein A coupled to immunogold in order to test their specificity. Thin sections of glycolmethacrylate embedded platelets before and after exposure to thrombin for 15, 30 and 60 s were stained with antibodies to tubulin and actin. Immunogold particles showed a high specificity for isolated MT coils stained for tubulin, modest intensity for actin, and none for vinculin. Gold particles were randomly distributed in thin sections of resting and activated platelets stained for actin. Immunogold was limited to the circumferential microtubule in resting platelets and constricted coils in thrombin-activated cells. The number of gold particles in areas of cytoplasm away from microtubules in platelets stained with antitubulin antibody increased slightly following thrombin activation, but the change was not significant. Results support the concept that microtubule coils supporting the discoid form of resting platelets do not dissolve following exposure of the cells to potent agonists. PMID- 3101493 TI - Clinical efficacy of desmopressin acetate for hemostatic control in patients with primary platelet disorders undergoing surgery. AB - Desmopressin acetate (DDAVP) is efficacious in patients with von Willebrand's disease. It additionally appears to have value in patients with uremic or aspirin induced platelet dysfunction. We report here three patients with primary platelet defects who had previously experienced grossly inadequate hemostasis to whom we administered DDAVP. Each successfully underwent surgical procedures with DDAVP as the only hemostatic agent. Although the mechanism of these salutary effects is unclear, DDAVP may exert an influence directly on the endothelium independent of correcting abnormalities of the factor VIII:von Willebrand complex associated with von Willebrand's disease. PMID- 3101495 TI - Effect of various nutrient ratios on the emulsion stability of total nutrient admixtures. AB - The emulsion stability of total nutrient admixtures (TNAs) containing various ratios of amino acids (AA):carbohydrate (CHO):fat (FAT) was studied. Eight different TNA formulations were prepared in duplicate using AA supplied as 8.5% crystalline AA (FreAmine III), CHO supplied as 70% dextrose injection, and FAT supplied as 10 or 20% lipid emulsion (Soyacal). The eight formulations represented AA:CHO:FAT ratios (v:v:v) of 2:1:1, 1:1:1, 1:1:1/2, and 1:1:1/4, respectively, with each lipid concentration. TNAs also contained identical concentrations of electrolytes, trace elements, vitamins, and heparin. TNAs were stored at 4 degrees C for 14 days and then at ambient temperature (22-25 degrees C) for another four days. All TNAs were analyzed for gross visual appearance, pH, osmolality, and particle size and distribution on day 0 and periodically throughout the study period. Particle size was measured by photon-correlation spectrometry and negative-phase light microscopy. Visual examination revealed the presence of creaming in all TNAs, which could be dispersed by gentle agitation. The pH of each TNA decreased slightly during the study period, while the osmolality showed little variation. The mean diameter of particles in the TNAs remained close to that in the original lipid emulsions; 95% of all particles in the TNAs were less than 0.454 micron in diameter, which is within the size range of natural lipid particles or chylomicrons. Based on examination of particle size, each TNA formulation was stable for 18 days under the conditions of this study. PMID- 3101494 TI - The French and North American phenotypes of pyruvate carboxylase deficiency, correlation with biotin containing protein by 3H-biotin incorporation, 35S streptavidin labeling, and Northern blotting with a cloned cDNA probe. AB - Cultured skin fibroblasts from 16 patients with either French or American pyruvate carboxylase (PC) deficiency were examined for their ability to incorporate 3H-biotin into proteins. Cell extracts were also examined for the presence of biotin-containing proteins with 35S-streptavidin, immunoreactive protein with anti-PC antibody, and PC mRNA by Northern blotting with a PC cDNA probe. All the North American presentation patients showed a 3H-biotin protein, a streptavidin protein, and an anti-PC precipitable protein at 125 kilodaltons on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cellular proteins. They also showed a detectable mRNA species for PC on Northern blotting. Of the French presentation patients, five showed very low or absent 3H-biotin protein, streptavidin protein, and anti-PC precipitable protein at 125 kilodaltons. Three French presentation patients showed PC protein to be present on the basis of these techniques. Similarly, five showed either very low or absent mRNA for PC on Northern blotting whereas three gave evidence of the presence of PC-specific mRNA. Thus, whereas the North American presentation of PC deficiency is associated with the presence of a mature biotin containing protein of the correct molecular weight, the French presentation may, in some (but not in all) cases, have both absent PC protein and absent PC mRNA. PMID- 3101496 TI - Abnormal testicular function in men with primary hypothyroidism. AB - Myxedema in men is thought to cause infertility and impotence. Testicular function was investigated in eight consecutive men with primary hypothyroidism (autoimmune thyroiditis in five patients and amiodarone therapy in three patients). All had impotence that preceded the onset of hypothyroidism and did not improve with thyroid therapy. Gonadal function tests showed a hypergonadotropic state in five patients and hypogonadotropic hypogonadism in three patients including one with no response to luteinizing hormone-releasing hormone. Luteinizing hormone bioactivity was decreased in six patients and increased in two subjects who also had increased luteinizing hormone immunoreactivity. Serum testosterone and testosterone/estradiol-binding globulin concentrations were low in four of the patients. It is concluded that abnormalities of gonadal function are common in men with primary hypothyroidism. PMID- 3101497 TI - Hypophosphatemic osteomalacia and adult Fanconi syndrome due to light-chain nephropathy. Another form of oncogenous osteomalacia. AB - Two patients, one with myeloma (Patient 1) and the other with probable chronic lymphocytic leukemia (Patient 2), had reduced renal tubular phosphate reabsorption in the absence of hyperparathyroidism together with other features of the Fanconi syndrome, as consequences of the nephropathy associated with light chain proteinuria. Both patients had hypophosphatemic osteomalacia, demonstrated for the first time in this condition by iliac bone histomorphometry after in vivo double tetracycline labeling, despite absence of bone pain or Looser zones. Neither patient was vitamin D-depleted, but plasma calcitriol level was normal in Patient 1 and low in Patient 2; only the latter patient had severe muscle weakness. Complete histologic correction of osteomalacia was achieved by treatment in accordance with the biochemical defects--oral phosphate therapy alone in Patient 1 and combined with calcitriol in Patient 2. Both patients are now symptom-free, five and three years after the initial diagnosis of bone disease and hematogenous malignancy. Thirteen previous instances of the same form of osteomalacia were reviewed; in most cases, the Fanconi syndrome developed before its probable cause became apparent. The Fanconi syndrome has also been reported in two cases of osteomalacia due to mesenchymal tumor, but not in osteomalacia associated with prostatic carcinoma. Light-chain nephropathy and consequent renal tubular dysfunction appears to be a third form of oncogenous osteomalacia. PMID- 3101498 TI - Adenocarcinoma of pancreas and duodenum associated with cutaneous neurofibromatosis. PMID- 3101499 TI - Lupus anticoagulant, thrombosis and thrombocytopenia in systemic lupus erythematosus. AB - Thirty-six patients were studied for the presence of the lupus anticoagulant and its possible clinical and laboratory associations. Seven patients were found to have the anticoagulant. These patients had a significantly increased incidence of both thromboembolic complications (5/7 vs. 2/29) and thrombocytopenia (4/7 vs. 4/29). None of them had a bleeding tendency. Except for these associations, patients with the anticoagulant did not differ from those without the anticoagulant by any demographic, clinical, or laboratory parameter. The present study confirms observations that SLE patients with the lupus anticoagulant have an increased risk of thrombosis. PMID- 3101500 TI - Estimating frequency of Kallmann syndrome among hypogonadic and among anosmic patients. AB - The frequency of Kallmann syndrome (hypogonadotropic hypogonadism and anosmia, HHA) was estimated in patients presenting with hypogonadism and patients with anosmia. Of 791 hypogonadal males 19 had HHA. The frequency of HHA was about 1:25 (n = 8/189) in outpatients questioned about their sense of smell, about 1:50 (n = 11/579) in patients whose blood samples were sent to us for chromosome analysis, and about 1:30 (n = 19/605) in males with hypogonadism and 46,XY chromosomes. The relation of patients with HHA to those with Klinefelter syndrome was 1:10 (n = 19/186). From 24 patients presenting with anosmia we found 1 hitherto undiagnosed case of HHA. The mean age at diagnosis was 24.8 and 24.9 years in our cases and cases from literature, respectively. These data provide evidence that Kallmann syndrome is not infrequent and that most patients remain undiagnosed until the third decade of life. Earlier diagnosis is emphasized by questioning each hypogonadal patient about his sense of smell because therapeutic success seems to be age dependent. PMID- 3101501 TI - Sitting easy: how six pressure-relieving devices stack up. PMID- 3101502 TI - Topical application of hyaluronic acid and chondroitin sulfate in the treatment of dry eyes. AB - Twenty patients with keratoconjunctivitis sicca used three different viscoelastic tear formulations and a polyvinyl alcohol artificial tear for two weeks each. Each formulation was used once every two waking hours in a controlled double masked study. Eighteen patients reported marked improvement over the course of the study, in terms of the severity of itching, burning, and foreign body sensation. Corneal staining and mucous strand formation were also reduced in patients with these manifestations. No formulation was preferred by a majority of patients or proved superior in treating signs of keratoconjunctivitis sicca. However, patients with low Schirmer test scores uniformly preferred a solution containing chondroitin sulfate, while patients with moderate Schirmer test scores tended to prefer a solution of polyvinyl alcohol or hyaluronic acid. PMID- 3101503 TI - Induction of hepatic veno-occlusive disease in dogs. AB - The authors attempted to induce hepatic veno-occlusive disease (VOD) in 64 dogs. Preparative treatments included combinations of total-body irradiation (TBI) or localized hepatic irradiation (LI) or both and chemotherapy consisting of dimethylbusulfan (DMB), L-phenylalanine mustard (L-PAM), methotrexate, or monocrotaline. VOD occurred infrequently in those dogs given 9.2 Gy TBI and DMB (1/10), TBI and/or LI (9.2-27 Gy) with L-PAM (2/36) or high dose methotrexate and LI (0/2). Specifically, VOD occurred in the dogs with a shorter interval between TBI and DMB or in the dog that received the glutathione reductase inhibitor, buthionine sulfoximide (BSO) before L-PAM. In contrast, among 17 dogs given monocrotaline, 8 developed VOD, particularly when used with L-PAM +/- irradiation (7/13). The major cause of death, early gastrointestinal toxicity, was further augmented by higher doses of irradiation, by shortening the interval between LI and L-PAM administration to less than 4 weeks, and administering BSO or monocrotaline before L-PAM. Gastrointestinal toxicity was lessened by giving low dose cyclophosphamide given before L-PAM. VOD can be produced in dogs especially with monocrotaline or BSO given before and L-PAM +/- irradiation. However, gastrointestinal toxicity renders the study of VOD beyond the acute phase difficult. Nevertheless, this approach appears useful for the study of VOD in other animals and for developing agents aimed at preventing VOD. PMID- 3101504 TI - New fossil anthropoids from the middle Miocene of East Africa and their bearing on the origin of the oreopithecidae. AB - Recent paleontological collections at the middle Miocene locality of Maboko Island in Kenya, dated at 15-16 million years, have yielded numerous new specimens belonging to at least five species of fossil anthropoids. The most common species of ape at the site, a medium-sized primate with a very distinctive dental morphology, clearly represents a previously undescribed taxon. When compared with other Miocene anthropoids from East Africa, it has its closest affinities with the poorly known species Rangwapithecus vancouveringi from the early Miocene locality of Rusinga Island. The species from Maboko Island is described here as belonging to a new genus of fossil anthropoid, to which "Rangwapithecus" vancouveringi is also referred. The new genus has a highly distinctive suite of derived characters of its molars and premolars, which it shares with Oreopithecus bambolii from the late Miocene of Europe. These synapomorphies indicate a close phyletic relationship between the East African species and Oreopithecus and form the basis for the inclusion of these taxa in a single family, the Oreopithecidae Schwalbe, 1915. In many respects, however, the East African forms are more conservative than Oreopithecus, and in a general sense they can be regarded as an intermediate grade between Oreopithecus and the more generalized early Miocene catarrhines, the proconsuloids. There is, therefore, good fossil evidence to indicate that the origins of the Oreopithecidae can be traced back to the early Miocene of Africa. PMID- 3101505 TI - Body weights in mixed species troops of Saguinus mystax mystax and Saguinus fuscicollis nigrifrons in Amazonian Peru. AB - An investigation of body weights of members of mixed species troops of Saguinus mystax mystax and Saguinus fuscicollis nigrifrons was conducted at the Rio Blanco Research Station in northeastern Peru. A total of 107 adult and subadult tamarin monkeys were trapped, measured, and released. Data collected indicate that mean body weights for adult male and female moustached tamarins are 564 gm and 626 gm, respectively, whereas for adult saddle-back tamarins these values are 412 gm and 411 gm. Subadults weighed 11-27% less than adults. Body weights recorded in this study are significantly greater than those previously reported for tamarins of the same species and age living in other areas of Amazonian Peru. We hypothesize that, in the case of moustached and saddle-back tamarins, advantages associated with feeding and foraging in mixed species troops facilitate greater efficiency in resource monitoring and result in the maintenance of larger body weights. PMID- 3101506 TI - Modulation of Na+-Ca2+ exchange in sarcolemmal vesicles by intravesicular Ca2+. AB - When cardiac sarcolemmal vesicles were incubated at 37 degrees C in 160 mM NaCl containing 0.5 mM CaCl2 and subsequently assayed for Na-Ca exchange activity, they exhibited a threefold increase in the initial rate of 45Ca2+ uptake (at 20 microM 45Ca2+) compared with vesicles incubated without added CaCl2. Removal of endogenous Ca2+ by incubation of the vesicles with 0.1 mM ethylene-bis(beta aminoethylether)N,N'-tetraacetic acid (EGTA) resulted in a 35% inhibition in exchange activity. The pretreatment with CaCl2 produced an acceleration of Na-Ca exchange activity rather than an increase in Ca2+ uptake due to Ca-Ca exchange. Pretreatment of the vesicles with CaCl2 lowered the apparent Km of the exchange system for Ca2+. The effects of the Ca treatment were reversed by subsequently incubating the vesicles with EGTA. In contrast to the effects of intravesicular Ca2+ on Nai-dependent Ca2+ uptake, external Ca2+ had no effect on Nao-dependent Ca2+ efflux. The results suggest that an understanding of the kinetics of the Na Ca exchange system may be hampered by the autoacceleration of exchange activity that occurs during initial rate measurements as Ca2+ accumulates within the vesicles. This phenomenon may contribute to the variability that exists among different vesicle preparations in their apparent Km values for Ca2+. PMID- 3101507 TI - Inhibition and activation of Na+-Ca2+ exchange activity by quinacrine. AB - Quinacrine either inhibited or stimulated Na-Ca exchange in cardiac sarcolemmal vesicles, depending on the experimental conditions. When present in the assay medium for Na-Ca exchange, quinacrine inhibited both Nai-dependent Ca2+ uptake (Ki = 50 microM) and Nao-dependent Ca2+ efflux. Quinacrine's inhibition of Ca2+ efflux was attenuated by high concentrations of Na+. Quinacrine also blocked Na Na and Ca-Ca exchange activities in the vesicles. The inhibitory effects of quinacrine on Na-Ca exchange activity are qualitatively similar to those reported previously for amiloride derivatives. When Na-loaded vesicles were preincubated with quinacrine and then assayed for Na-Ca exchange in a quinacrine-free medium, stimulation of exchange activity was observed. This stimulation was reversible on the removal of bound quinacrine and involved in a reduction in the apparent Km for extravesicular Ca2+. Stimulation of exchange activity under these conditions was also observed with the lipophilic cation tetraphenylphosphonium. Since Ca2+, quinacrine and tetraphenylphosphonium all bind strongly to sarcolemmal membranes, it is suggested that the observed stimulation of exchange activity involves a local electrostatic effect of the bound cations in accelerating a rate-limiting step in the reaction mechanism for Na-Ca exchange. PMID- 3101508 TI - Acute effect of calcium and insulin on hyperfiltration of early diabetes. AB - We examined the effect of calcium administration on renal hyperfiltration in streptozotocin-treated diabetic rats. Rats were studied 7-10 days after streptozotocin injection. Intrarenal infusion of CaSO4 in Ringer's solution had no effect on the hyperfiltration of the diabetic kidney. Infusion of insulin in a dose that did not effect hyperglycemia also had no effect on the hyperfiltration. However, when insulin and calcium were infused together, a rapid decrease in glomerular filtration rate, single-nephron filtration rate, glomerular hydraulic pressure, and renal plasma flow occurred. The contralateral control kidney was unaffected. Verapamil infusion had no significant effect in untreated diabetic rats, but immediately reversed the vasoconstriction induced by insulin plus calcium. Similar intrarenal insulin and calcium infusions had no effect in euvolemic or chronically salt-loaded nondiabetic rats. The observations indicate that renal vascular cells (probably preglomerular) are hyperresponsive to calcium in early insulin-dependent diabetes mellitus and that this response requires insulin. We suggest that decreased renal vascular tone in early insulin-dependent diabetes mellitus may be due in part to defective transmembrane calcium flux across vascular smooth muscle cells. Insulin appears to be required for calcium entry or mobilization, to initiate renal vascular smooth muscle contraction in diabetes. PMID- 3101509 TI - Vital microscopy of islet blood flow: catecholamine effects in normal and ob/ob mice. AB - The pancreatic microcirculation in noninbred ob/ob mice and normal controls was visualized in a fluorescence microscope and examined for responses to intravenous infusions of epinephrine or norepinephrine. Evaluations of coded video recordings revealed a smooth dose-response relationship and validated a semiquantitative method of analysis. In ob/ob mice the islet microcirculation was markedly and reversibly inhibited by 0.14-4 micrograms of epinephrine X min-1 X kg body wt-1; the flow was almost totally stopped at the highest infusion rates. Capillary flow in the exocrine pancreas appeared unaffected, except for some inhibition at 4.0 micrograms X min-1 X kg-1. Norepinephrine was less potent an inhibitor of islet blood flow. Normal lean mice exhibited minor responses to 1-11.3 micrograms of epinephrine X min-1 X kg-1; in most cases there was no visible effect. It is concluded that there is a selective regulation of blood flow through the endocrine portion of the pancreas and that the islet microcirculation is hypersensitive to catecholamines in noninbred ob/ob mice. A defective inhibitory influence from the brain may play a role in the development of excessive hyperinsulinemia in ob/ob mice. PMID- 3101510 TI - Carbachol regulates cholecystokinin receptor on pancreatic acinar cells. AB - We have examined the effect of carbamylcholine on the binding of cholecystokinin (CCK) to dispersed acini from rat pancreas. The CCK receptor on pancreatic acini possesses two classes of binding sites. Simultaneous addition of carbamylcholine inhibited binding of CCK to acini due to an apparent loss of high affinity CCK binding sites. Atropine prevented the inhibitory effect of carbamylcholine, whereas calcium ionophore A23187 did not alter binding of CCK. 12-O tetradecanoylphorbol-13-acetate (TPA) inhibited binding of CCK in the same manner as carbamylcholine. Inhibition by carbamylcholine was reversible and the recovery was time dependent. By contrast, inhibition of binding of CCK by TPA did not reverse after a 60-min incubation without the agent. These findings, at least in part, account for the inhibition of the CCK-induced stimulation of amylase secretion by carbamylcholine. The action of TPA on binding of CCK suggests the possible involvement of the activation of protein kinase C in the inhibition of binding. PMID- 3101511 TI - Role of GIP and insulin in glucose-induced changes in intestinal motility patterns. AB - This study was designed to correlate the intestinal motility patterns with duodenal glucose loads and the increments in plasma gastric inhibitory peptide (GIP) and insulin levels after these loads or after the administration of exogenous hormones in conscious dogs. Isotonic glucose instilled intraduodenally at lower loads (5.2-42.4 mmol/h) only caused a moderate increase in spike activity, but at higher loads (84.8 mmol/h) it disrupted migrating myoelectric complexes (MMC), being accompanied by marked increases in plasma GIP and insulin levels. Duodenal loads of isotonic mannitol resulted in similar motility changes but without alteration in plasma GIP or insulin. Hypertonic glucose (20%) in the duodenum also caused an increase in spike activity, and at higher loads (72 mmol/h or higher) it disrupted MMCs and resulted in significant increments in plasma GIP and insulin levels. Physiological doses of exogenous GIP (25-400 pmol X kg-1 X h-1) or insulin (12-24 mU X kg-1 X h-1) did not affect the motility pattern, but at higher doses, raising plasma hormone over the levels occurring after a mixed meal, GIP (400 pmol X kg-1 X h-1) increased significantly the MMC interval, whereas insulin (48-96 pmol X kg-1 X h-1) induced a fed-like motility pattern. Intravenous 20% glucose (72 mmol/h) caused a marked rise in plasma insulin (but not GIP) levels but failed to affect the intestinal motility as did 20% mannitol infused intravenously in the same dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101512 TI - Factors affecting proximal tubular reabsorption during development. AB - Studies performed in several animal species have demonstrated that glomerulotubular balance is maintained throughout development despite the many changes that occur in the factors known to control it. In an attempt to understand the nature of this phenomenon we quantified the magnitude and described the profile of these changes in guinea pigs. The changes in physical forces were assessed from measurements of hydrostatic and oncotic pressures, whereas those in the permeability characteristics of the proximal tubule epithelium were estimated from permeance to macromolecules of graded radii, histologic measurements of the intercellular channels, and measurements of end proximal ratio of tubular fluid-to-plasma osmolality (TF/Posm). Between 1 and 50 days of age the net pressure for reabsorption increased from 15.0 to 30.9 mmHg (P less than 0.01, n = 15) with the major change occurring during the first 2-3 wk of postnatal life. The urinary recovery of inulin, sucrose, and creatinine, injected in the early segment of proximal tubules did not vary with age. The urinary recovery of mannitol (MW 180 daltons, Stokes-Einstein radius 4.0 X 10( 10) m) increased from 92% at birth to 100% at 49 days of age (P less than 0.001, n = 24), consistent with a decrease of approximately 0.5 X 10(-10) m in the luminal openings of the paracellular channels. The length of the zonulae occludens and the width of the intercellular channels did not change during this period; however, the length of the channels increased from 5.0 +/- 0.17 to 8.9 +/ 0.48 micron (P less than 0.01, n = 16). These changes should result in an increase in resistance across the intercellular channels. Consistent with this assertion is the observation that the mean TF/Posm of the fluid collected toward the end of the proximal convoluted tubule decreased as a function of age from 1.05 at day 2 to 0.98 at day 80 (P less than 0.001, n = 24). The findings support the hypothesis that during early postnatal life glomerulotubular balance is made possible by a high permeability of the proximal tubule, which compensates for the low net reabsorptive pressure. As the animal matures and the proximal tubule epithelium becomes tighter, for glomerulotubular balance to be maintained, an increase in the number of intercellular channels and in the active transport of sodium need to be postulated. PMID- 3101513 TI - PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and TxB2 synthesis along the rabbit nephron. AB - The capacity of synthesis of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 6-keto-PGF1 alpha, and thromboxane (TxB2) along the rabbit nephron was determined. A sensitive enzyme immunoassay was applied to isolated nephron segments, from the glomerulus to the terminal collecting tubule. The three prostaglandins and thromboxane (PG) were measured on the same samples after incubation in the presence of arachidonic acid. In the glomerulus, PGE2 synthesis (29.4 +/- 3.3 pg X glomerulus-1 X 30 min-1) represented 60% of the sum of the four PGs. PGF2 alpha and 6-keto-PGF1 alpha represented 22 and 17%, respectively, and TxB2 1.4%. The contribution of each PG to tubular synthesis was different, since at least 90% of PG synthesis consisted of PGE2. In the medullary collecting tubule (MCT), by far the major tubular site of PG synthesis, it was 809.6 +/- 140.8 pg X mm-1 X 30 min-1 for PGE2, 17.7 +/- 7.2 for PGF2 alpha, 8.3 +/- 1.9 for 6-keto-PGF1 alpha and 0.24 +/- 0.08 for TxB2. These relative proportions were roughly respected all along the tubule. Values were much lower in the convoluted and straight portions of the proximal tubule (proximal convoluted tubule: PGE2 8.2 +/- 2.0, PGF2 alpha 0.4 +/- 0.06, 6-keto-PGF1 alpha 0.26 +/- 0.04, TxB2 0.017) and the medullary and cortical thick ascending limb of the loop. They increased regularly along the distal structures of the tubule (light portion of the cortical collecting tubule (CCT1): PGE2 228.3 +/- 20.4, PGF2 alpha 4.34 +/- 0.6, 6-keto-PGF1 alpha 1.8 +/- 0.3, TxB2 0.22 +/- 0.07).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101514 TI - Effects of cord compression on fetal blood flow distribution and O2 delivery. AB - We used the radionuclide microsphere technique in nine fetal lambs to examine the effect of partial cord compression on distribution of cardiac output and O2 delivery to fetal organs and venous flow patterns. With a 50% reduction in umbilical blood flow the fraction of fetal cardiac output distributed to the brain, heart, carcass, kidneys, and gastrointestinal tract increased. Pulmonary blood flow fell. O2 delivery to the brain and myocardium was maintained but was reduced to peripheral, renal, and gastrointestinal circulations. Hepatic blood flow decreased and O2 delivery fell by 75%. The proportion of umbilical venous blood passing through the ductus venosus increased from 43.9 to 71.8%. The preferential distribution of ductus venosus blood flow through the foramen ovale was enhanced (29.4 vs. 47.2%) and the proportion of O2 delivery to upper body organs derived from the ductus venosus increased (33.2 vs. 49.4%). Abdominal inferior vena caval blood flow increased, and it was also preferentially distributed through the foramen ovale (21.9 vs. 44.2%) and constituted the major fraction of the arterial blood supply to the upper body organs (16.5 vs. 36.4%). Thus cord compression modified the distribution of cardiac output and the patterns of venous returns in the fetus. This pattern of circulatory response differs from that observed with other causes of reduced O2 delivery. PMID- 3101515 TI - Ontogeny of 6-keto-PGF1 alpha synthesis in rabbit aorta and the effect of premature weaning. AB - A systematic study of the ontogeny of aortic 6-ketoprostaglandin F1 alpha synthesis from birth to adult life and the effect of premature weaning on this process was investigated in rabbits. Prostacyclin (PGI2) synthesis by both endogenous and exogenous arachidonic acid and its relation to aortic arachidonic acid content was determined. It was found that 1) PGI2 synthesis from endogenous arachidonic acid increased with age, whereas 2) PGI2 synthesis from exogenous arachidonic acid decreased. This correlated with a decrease in the incorporation of [14C]arachidonic acid into phospholipids with age. Aortic arachidonic acid concentration did not change from birth until 3 wk of life but increased markedly by 5 wk of age. Premature weaning caused a decrease in the synthesis of aortic PGI2 and in aortic arachidonic acid concentration initially, but the changes did not persist in later life. These studies suggest that the utilization of exogenous arachidonic acid by aorta decreases after birth perhaps due to maturity of the enzyme systems that synthesize and utilize endogenous substrates. PMID- 3101516 TI - Effect of theophylline on adenosine production in the canine myocardium. AB - Adenosine is thought to participate in local regulation of coronary blood flow. However, competitive antagonists of adenosine fail to block myocardial active hyperemia. We examined the effect of locally administered theophylline on active hyperemia and myocardial adenosine production during intracoronary isoproterenol infusion in the dog heart. Isoproterenol decreased coronary resistance and increased myocardial adenosine production. Infusion of theophylline at a rate that attenuated the vasodilator response to exogenously administered adenosine failed to attenuate the increase in coronary blood flow produced by isoproterenol. However, theophylline plus isoproterenol produced greater increases in myocardial adenosine production than isoproterenol alone. The curves relating resistance and adenosine in the presence of theophylline fell to the right of those in the absence of theophylline. These findings suggest that the failure of theophylline to attenuate isoproterenol hyperemia in the dog heart results at least in part from an increase in adenosine concentration at the arteriole to a level beyond that blocked by this competitive antagonist and that adenosine may in fact play a role in isoproterenol-induced active hyperemia. PMID- 3101517 TI - Vasopressin responses to asphyxia and hemorrhage in newborn pigs. AB - Vasopressin may be important in maintenance of arterial pressure and redistribution of cardiac output in hypotensive and asphyxiated newborns. We used chronically instrumented, unanesthetized, 4-day-old pigs to investigate the effects of hypotensive hemorrhage and asphyxia on plasma vasopressin concentration and to determine the effects of cyclooxygenase inhibition on these responses. Asphyxia [arterial O2 partial pressure (PaO2) = 40-50 Torr, arterial CO2 partial pressure (PaCO2) = 60-80 Torr) increases plasma lysine vasopressin (LVP) from 2.2 +/- 0.8 to 52.4 +/- 15.0 microU/ml. Neither the baseline nor stimulated plasma LVP was affected by indomethacin (5 mg/kg) or meclofenamate (5 mg/kg). Hemorrhage (30 ml/kg) increased plasma LVP from 2.8 +/- 0.8 to 163.4 +/- 28.1 (20 min) and 135.1 +/- 18.5 microU/ml (60 min). The effects of vehicle and indomethacin (5 mg/kg) 20 min after hemorrhage on plasma LVP 60 min after hemorrhage were not different. Changes in plasma vasopressin caused by asphyxia and hemorrhage in the unanesthetized newborn pig are similar to the responses observed in adults of other species. This study does not suggest that prostanoids are involved in these responses in newborn pigs. PMID- 3101518 TI - Cardiovascular effect of V1 vasopressinergic blockade during acute hypercapnia in conscious rats. AB - Experiments were performed to test the possible involvement of arginine vasopressin (AVP) in the systemic cardiovascular responses to acute hypercapnic acidosis in conscious chronically instrumented rats. Exposure to 6% CO2 caused arterial PCO2 to rise from 34 +/- 2 to 53 +/- 1 Torr. This level of hypercapnia was associated with a consistent bradycardia; however, cardiac output, blood pressure, and total peripheral resistance were not significantly affected. Administration of 10 micrograms/kg iv of the specific V1 vasopressinergic antagonist d(CH2)5Tyr(Me)AVP during 6% CO2 had no effect on any of the measured hemodynamic variables. Furthermore, d(CH2)5Tyr(Me)AVP also had no effect in normocapnic control animals. Exposure to a more severe level of hypercapnia (10% CO2, arterial PCO2 = 89 +/- 1 Torr) resulted in marked hemodynamic alterations. Profound bradycardia and decreased cardiac output in addition to increases in mean arterial blood pressure and total peripheral resistance were observed. V1 vasopressinergic antagonism during 10% CO2 had no effect on heart rate but greatly increased cardiac output. In addition, blood pressure fell and resistance was decreased below prehypercapnic levels. These data suggest that a number of the hemodynamic alterations associated with severe hypercapnic acidosis in the conscious rat may be mediated by the peripheral cardiovascular effects of enhanced AVP release. PMID- 3101519 TI - Effect of parathyroid hormone on transport by toad and turtle bladder. AB - We recently demonstrated that parathyroid hormone (PTH) inhibited both vasopressin- and cyclic AMP-stimulated water transport in the toad bladder. This was associated with an increase in calcium uptake by isolated epithelial cells. We postulated that PTH exerts its action on H2O transport by directly stimulating calcium uptake. The current study was designed to compare the effects of PTH and the calcium ionophore, A23187, on H2O and Na transport and H+ secretion in toad and turtle bladders. In toad bladder, PTH and A23187 decreased arginine vasopressin (AVP)-stimulated H2O flow and short-circuit current (SCC) after 60 min serosal incubation. In turtle bladder A23187 decreased SCC to 79.3 +/- 3.6% of base line (P less than 0.05), and significantly decreased RSCC as well. PTH had no effect on SCC or H+ secretion in turtle bladders. Both PTH and A23187 increased 45Ca uptake in toad bladder epithelial cells; only A23187 increased 45Ca uptake in the turtle bladder. The different action of PTH in these two membranes, compared with that of the calcium ionophore, illustrates the selectivity of PTH on membrane transport. PTH increases calcium uptake and decreases transport only in a hormone-sensitive epithelium, whereas the ionophore works in virtually all living membranes. The mode of action of these two agents to increase calcium uptake is, therefore, likely different. PMID- 3101520 TI - Fetal responses to altered maternal oxygenation in rhesus monkey. AB - The purpose of this study was to establish (in the primate) maternal-fetal relations for blood gas parameters and certain related aspects of fetal cardiovascular function with the mother at rest and subjected to a range of altered states of oxygenation. In 10 chronically cannulated rhesus monkey fetuses, with the mother lightly sedated with phencyclidine, on each of two days we studied the effects of maternal hypoxia and hyperoxia [(15, 10, and 100% maternal fractional concentration of inspired O2 (FIO2)] on maternal and fetal pH, PCO2, PO2 and O2 concentration (CaO2) and fetal heart rate, blood pressure, and superior vena caval (SVC) flow distribution. We observed a linear correlation between maternal and fetal pH and PCO2. There was evidence of a fetal metabolic acidosis with 10 but not with 15% hypoxia. Maternal-fetal PO2 and CaO2 correlated in curvilinear and linear fashion, respectively. Maternal-fetal CaO2 difference was maintained within a narrow range (2.7-4.8 vol%) for various states of maternal oxygenation, showing a tendency to expand only with severe (10%) hypoxia. Results indicate that quantitative delivery of O2 to the placenta was of paramount importance as a determinant of O2 transfer to the fetus and are compatible with a "concurrent flow" model of transplacental O2 diffusion. Fetal heart rate decreased progressively with 15 and 10% hypoxia. SVC flow to lungs and placenta varied reciprocally with changes in fetal oxygenation. As indicated by distribution to the heart, shunting of SVC flow through the foramen ovale was modest at rest, with no evident change in response to fetal hypoxemia. PMID- 3101521 TI - Total CO2 flux in isolated collecting tubules during carbonic anhydrase inhibition. AB - These studies evaluated the effects of sodium transport inhibitors on total CO2 flux (JtCO2) in the rabbit cortical collecting tubule after inhibition of carbonic anhydrase. When ouabain was added to tubules during carbonic anhydrase inhibition, reabsorptive JtCO2 rose and potential difference (PD) decreased. Amiloride added to perfusate after carbonic anhydrase inhibition decreased PD and did not alter JtCO2. If ouabain was added to an ethoxyzolamide-treated tubule with amiloride present in perfusate, no effects were detectable. Amiloride added to the bath of ethoxyzolamide-treated tubules in high concentration (10-3 M), decreased potential and increased JtCO2. If amiloride was added to the bath of cortical collecting tubules from fasted rabbits, JtCO2 rose. This response was not seen in cortical tubules from fed animals or in medullary collecting tubules. These data demonstrate the existence of carbonic anhydrase-independent acidification in this segment in vitro. The data from studies with amiloride in the presence of intact carbonic anhydrase are consistent with action on a basolateral sodium-proton exchange mechanism. A cellular model that postulates a basolateral sodium-proton exchanger in an acidifying cell is offered. PMID- 3101522 TI - Acid-base balance in ducks (Anas platyrhynchos) during involuntary submergence. AB - Measurements of all the major independent variables [arterial CO2 tension (PaCO2); strong-ion difference ([SID]), and total protein content, which approximate total weak acid concentration in plasma] are essential for understanding changes in acid-base balance in plasma. During involuntary submergence of 1, 2, or 4 min, PaCO2 in ducks increased and arterial pH (pHa) decreased. During 1-min dives there were no significant changes in any strong ions. In both 2- and 4-min dives, there was a significant increase in [lactate-], but because of an increase in equal magnitude of [Na+], [SID] did not change. During recovery from all dives the plasma remained acidotic for several minutes, although PaCO2 fell below predive levels in less than 1 min. [Lactate-] increased in the recovery period. There were no changes in total protein content during submergence or recovery. Breathing 100% O2 before 2-min dives caused a reduction in [lactate-] production and release during and after the dive, although due to a marked increased in PaCO2, pHa fell as low as in 4-min dives after breathing air. After 1 min of recovery, pHa returned to normal along with the restoration of the predive level of PaCO2. We conclude that the acidosis during involuntary submergence is due solely to an increase in PaCO2, whereas in recovery it is caused by decreased [SID]. PMID- 3101523 TI - Amniotic fluid volume regulation: basal volumes and responses to fluid infusion or withdrawal in sheep. AB - To better understand the mechanisms that regulate amniotic fluid (AF) volume, we measured AF volume and the rates of fetal swallowing and urination in 33 pregnant sheep at 124-142 days gestation. In four of five ewes over 9-18 days, the spontaneous changes in amniotic fluid volume correlated positively with urine flow rate and negatively with the rate of swallowing (R = 0.686, P less than 0.01), such that 47% of the AF volume changes could be attributed to changes in rates of urination and swallowing. Following infusion of one liter of isotonic amniotic saline (n = 12) or mannitol (n = 5), AF volume increased 110%, and after 24 h returned to the control value in the saline group but it remained elevated 59% above control in the mannitol group. AF sodium was unchanged following saline infusion but remained reduced following mannitol. Following withdrawal of 61% of AF over 20-40 min, AF volume averaged 51 and 71% of control at 24 and 48 h, respectively, whereas AF sodium was unchanged. Variations in rates of fetal swallowing or urine formation could not explain the entire changes in AF volume following either the volume infusion or withdrawal. These data suggest that AF volume is regulated within a relatively narrow range and fetal urine formation and swallowing together and transplacental fluid flux each appear to contribute equally to the regulation of AF volume. PMID- 3101524 TI - The efficacy of antiinflammatory medication in the treatment of the acutely sprained ankle. AB - The value of nonsteroidal antiinflammatory drugs in the treatment of various sports-related injuries has been investigated by several groups. Despite these efforts, the experimental results are difficult to interpret, and very few investigations have focused on a single injury type in the acute phase. A double blind study compared ibuprofen at a dose of 2,400 mg per day and a placebo in the 1st week of treatment of 61 acute ankle sprains with varying degrees of severity. Medical evaluation by the same physician was performed on the 1st, 4th, 8th, and 28th day following the injury. Subjective evaluation of pain, number of painful ligaments at palpation, passive mobilization induced pain, edema, and functional incapacity served as the clinical parameters. Although there were trends indicating a superiority of effectiveness in the treatment group, the differences between groups were not statistically significant. PMID- 3101526 TI - Antibody to Crimean-Congo hemorrhagic fever virus in wild mammals from southern Africa. AB - Crimean-Congo hemorrhagic fever (CCHF) virus is becoming increasingly recognized as an important human pathogen in southern Africa. In order to determine the role of wild mammals in the natural ecology of the virus, sera from 3,772 wild mammals of 87 species and from 1,978 domestic dogs collected in South Africa and Zimbabwe between 1964 and 1985 were tested for antibody to CCHF virus by reversed passive hemagglutination inhibition (RPHI) and by indirect immunofluorescence (IF). Antibody was found to be highly prevalent in large mammals in the Orders Artiodactyla and Perissodactyla such as giraffe, Giraffa camelopardalis (3/3 positive), rhinoceros, Ceratotherium simium and Diceros bicornis (7/13), eland, Taurotragus oryx (59/127), buffalo, Syncerus caffer (56/287), kudu, Tragelaphus strepsiceros (17/78), and zebra, Equus burchelli (16/93). In small mammals antibody was found in the sera of 40/293 hares, 22/1,305 rodents, and 1/74 wild carnivores, but not in 522 primates, 176 insectivores, or 19 hyrax. Antibody was also found in the sera of 118/1,978 domestic dogs. The species of wild mammal in which antibody was distributed (with highest antibody prevalence in hares and large herbivores) reflects the feeding preference of immature and adult ticks of the genus Hyalomma, suggesting that Hyalomma sp. are the principal CCHF vectors in the wild. PMID- 3101525 TI - Epidemiologic and clinical features of Crimean-Congo hemorrhagic fever in southern Africa. AB - Following the diagnosis in 1981 of the first case of Crimean-Congo hemorrhagic fever (CCHF) in South Africa, an antibody survey was undertaken on cattle sera to determine the distribution of the virus and specific diagnostic tests were routinely applied to specimens from suspected cases of hemorrhagic fever to establish the medical significance of its presence. Antibody to CCHF virus was demonstrated by reversed passive hemagglutination-inhibition technique in 2,460/8,667 (28%) cattle sera and in 140/180 herds tested in South Africa, as well as in 347/763 (45%) cattle sera and in 32/34 (94%) herds tested in Zimbabwe. The antibody was found in all major cattle farming areas, but was of low prevalence along the southern coast where 2 of the 3 species of Hyalomma tick which occur in South Africa are absent. From February 1981 to January 1986, inclusive, 29 indigenous cases of CCHF were diagnosed in 16 outbreaks which arose in various locations throughout South Africa. A further 2 imported cases of CCHF arose in Zaire and Tanzania. The clinical features of infection conformed to the classical descriptions of CCHF in the Soviet Union. The fatal outcome in 11/31 cases indicates that the African disease is no less severe than that which occurs in Eurasia. It is inferred that the virus is widespread in all countries in Africa and Eurasia which lie within the limits of world distribution of ticks of the genus Hyalomma. PMID- 3101527 TI - Peripheral nervous system damage in experimental chronic Chagas' disease. AB - Electromyographic and histopathologic studies were performed in Rockland mice chronically infected with CA-I Trypanosoma cruzi strain. At 4 months post infection the emg failed to show spontaneous activity, but a diminished interference pattern was detected in half of the infected group, while mean motor unit potential amplitude and duration were increased, compared with controls. An active denervation was observed at 6 months which persisted up to 9 months, when motor unit potential showed a significantly lower mean activity and duration. At 12 months most of the infected mice developed a reduced interference pattern, polyphasic motor unit potential increase with higher duration and amplitude than controls. Histopathologic studies showed myositis with perivascular involvement as well as intramuscular neuritis, especially at 4 and 12 months. Atrophic and hypertrophic fibers were seen. Few amastigote nests were detected. Inflammatory neuropathy with the demyelinated fibers and scanty axonal degeneration were the most common features in all infected mice. Mild myelinated fiber loss was only evident after 12 months. Endoneural parasites were seen only in the perineural macrophagic cells. These findings suggest that the neurogenic mechanism involved in the pathogenesis of muscle damage in this experimental model of chronic Chagas' disease consistently has been overlooked. The features registered here suggest that T. cruzi-infected mice developed a bimodal muscle denervation with an early acute period at any time before month 4, followed by reinnervation with a subsequent new acute denervation period by month 6, followed in turn by a slow later reinnervation. PMID- 3101528 TI - Effects of the ornithine decarboxylase inhibitors DL-alpha difluoromethylornithine and alpha-monofluoromethyldehydroornithine methyl ester alone and in combination with suramin against Trypanosoma brucei brucei central nervous system models. AB - Two ornithine decarboxylase inhibitors, DL-alpha-difluoromethylornithine (eflornithine; DFMO) and a-monofluoromethyldehydroornithine methyl ester (delta MFMO X CH3) were compared in their ability to cure two distinct Trypanosoma brucei brucei central nervous system murine model infections. Both inhibitors cured the TREU 667 and LUMP 1001 isolates if used in combination with a single (20 mg/kg) injection of suramin, a trypanocide in current clinical use. The curative dose of delta MFMO X CH3 in combination with suramin was 1.09 g/kg/day, administered in the drinking water for 14 days; used with suramin, the curative dose of DFMO was 5.3 g/kg/day for 14 days (5 times the delta MFMO X CH3 dose required). In host animals, delta MFMO X CH3 was not toxic and was accumulated by trypanosomes 6-8 times faster than DFMO. Since DFMO by itself has been highly effective against T. b. gambiense infections in humans (12-15 g/day for 6 weeks) the present data suggest that delta MFMO X CH3 might be effective in a shorter regimen and at lower doses. PMID- 3101529 TI - Stimulation of peripheral blood mononuclear cells from patients with schistosomiasis mansoni by living and fixed schistosomula, and schistosomular membrane extracts and vesicles. AB - Several antigenic preparations derived from Schistosoma mansoni schistosomula were compared as immunogens in proliferation assays utilizing peripheral blood mononuclear cells (PBMN) from patients with chronic intestinal schistosomiasis mansoni. Living and fixed schistosomula, either irradiated or nonirradiated, and freshly transformed or 24 hr cultured worms were found to induce very similar proliferative responses of patients' PBMN. Two schistosomulum surface membrane preparations were also compared. Membrane vesicles from schistosomula were found to elicit mean proliferative responses similar to those stimulated by a CaCl2 extracted tegument preparation and to do so at lower total protein concentrations. However, the responses to membrane vesicles were somewhat more variable. When saline extracts from schistosomular bodies submitted to these two treatments were used as stimulants in parallel PBMN cultures it was found that vesiculation more effectively removed antigens involved in the stimulation of PBMN. Broken vesicles were less stimulatory than intact ones. This suggests that the manner in which membrane antigens are presented to antigen processing cells is critical. Incubation of schistosomula at 37 degrees C, but not 4 degrees C in medium containing 10% fetal calf serum from 3 to 48 hr decreased the capacity of the membrane to produce vesicles when treated with high salt solution. PMID- 3101530 TI - Immediate postoperative jejunostomy feeding. Clinical and metabolic results in a prospective trial. AB - A prospective clinical trial was designed to evaluate the efficacy of postoperative jejunostomy feedings using high (44 percent) and low (15 percent) branched-chain amino acid elemental diet formulations compared with no jejunostomy feedings in a homogeneous surgical population. Twenty-eight patients undergoing radical cystectomy and ileal diversion were randomized to the high branched-chain amino acid formula (11 patients) or the low branched-chain amino acid formula (9 patients). Eight patients received a 5 percent dextrose in water solution intravenously and served as a control group. Mean caloric intake per day in each group was 1,543 calories, 1,697 calories, and 550 calories, respectively; whereas the mean nitrogen intake of each group was 6.5 +/- 2.1 g/day, 8.2 +/- 2.4 g/day, and 0 g/day, respectively. Mean weight changes were minus 0.7 percent, 0.7 percent, and minus 0.3 percent, respectively. The mean daily nitrogen balance was minus 1.6 +/- 3.5 g/day, minus 1.1 +/- 4.4 g/day, and minus 6.6 +/- 1 g/day (p less than 0.001). Five patients (25 percent) in the jejunostomy groups progressed to an oral diet more rapidly than the control group, but gastrointestinal complications occurred in 11 patients (55 percent). Immediate postoperative jejunostomy feedings resulted in improved nitrogen balance compared with the control group values, but no metabolic advantage was noted by infusing a high branched-chain amino acid formula. Improved return to normal gastrointestinal function was noted in 25 percent of jejunostomy patients, but the gastrointestinal complications noted limited the overall usefulness of this technique. PMID- 3101531 TI - [Artificial feeding using the duodenojejunal route]. PMID- 3101532 TI - [Late results of using plasmapheresis. Prevention of hemolytic disease of the fetus and newborn infant in Rh-compromised pregnancy]. PMID- 3101533 TI - Plasma fatty acid pattern including diene-conjugated linoleic acid in ethanol users and patients with ethanol-related liver disease. AB - The level of conjugated dienes (CD) in the serum, conjugated linoleic acid isomer in the phospholipid fraction [18:2(9, 11)], and the fatty acid profile in both the serum and in the separated lipid classes were analyzed in current and previous alcohol abusers and in patients with alcoholic liver disease. None of the subjects consumed alcohol for at least 2-3 days prior to blood collection for analysis of lipids. There was no significant difference in CD or in the absolute level of 18:2(9, 11) among the groups, whereas the 18:2(9, 11)/18:2(9, 12) molar ratio was significantly elevated in patients with liver disease. Fatty acid analysis of the whole plasma extract showed that the absolute level of arachidonic acid increased from 4.8 +/- 3.5 mg/dl (n = 9) in lifelong abstainers to 13.4 +/- 4.0 (n = 8) in current ethanol abusers, and its relative level (related to the total fatty acids) from 1.73 +/- 1.34 to 4.55 +/- 1.01 in the same groups. An increased proportion of linoleic acid in the triglyceride and phospholipid fractions from current abusers and patients with liver disease was also found; the percentage of 18:2 in phospholipids increased from 5.4 +/- 5.0 (n = 8) in lifelong abstainers to 14.3 +/- 3.9 (n = 8) in current abusers and 12.7 +/- 2.2 (n = 10) in patients with liver disease. The percentage of 16:0 was significantly lower in the phospholipids of current abusers as compared to lifelong abstainers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101534 TI - Allergy to rabbits. I. Specificity and non-specificity of RAST and crossed radioimmunoelectrophoresis due to the presence of light chains in rabbit allergenic extracts. AB - Investigations have been carried out into the presence of antibody light chains in rabbit allergenic extracts and the interference in RAST and crossed radioimmunoelectrophoresis (XRIE) caused by antibodies directed against them. A "non-specific" uptake of radioactivity in XRIE has been demonstrated to be caused by direct cross-linking of the 125I rabbit anti-human IgE by the sheep antibodies in the immunoprecipitate of rabbit light chains. Preincubation with normal rabbit serum blocked this direct uptake of the labelled antibody and enabled specific IgE uptake on the light chains to be demonstrated for rabbit allergic sera. Verification of the allergenicity of the light chains was obtained from a specific light chain RAST. Elution from a Sephacryl S-200 gel filtration column indicated a MW of approx. 50 Kd and confirmation of the component as light chain dimers, not Fab fragments, was obtained by allotyping for loci present on heavy chains and light chains in the Fab region. Light chains were detected in urine from rabbits of all ages and in an extract of dust collected in a rabbit housing area. No background staining was observed in XRIE using rabbit antisera, either with rabbit allergic sera with specific IgE or with a human serum containing specific IgG antibodies to rabbit IgG. This latter serum also showed no evidence of uptake on all immunoprecipitates in systems using rabbit antisera, and did not give false positive RAST results when the labelled rabbit anti-human IgE contained unlabelled rabbit IgG. Those sera with specific IgE to light chains showed no uptake in XRIE using rabbit antisera, indicating that the IgE was possibly specific for epitopes revealed by the dissociation of the whole IgG molecule. PMID- 3101536 TI - [Effect of various types of artificial respiration on raised intracranial pressure, associated with acute alcoholic intoxication]. AB - The effects of spontaneous respiration and mechanical ventilation on ICP were examined by investigating the interaction between elevated pressure and alcohol intoxication. 200 ml ethanol 48% were infused in 11 young pigs with elevated cerebral pressure during mechanical ventilation (Group 1), 7 young pigs with elevated intracranial pressure during spontaneous respiration (Group 2), and 4 young pigs without elevated intracranial pressure during spontaneous respiration (Group 3). While the behaviour of intracranial pressure during mechanical ventilation in the animals from Group 1 was inhomogeneous with a tendency to rise (29 mmHg to 34 mmHg), intracranial pressure (28 mmHg to 55 mmHg) increased dramatically in Group 2. This increase was associated with a sharp rise of paCO2 (37.6 mmHg to 73.3 mmHg) and a decline of paO2 (74 mmHg to 13 mmHg). None of the animals in Group 2 survived. paCO2 also rose in alcoholized animals without elevated ICP (Group 3) (41.9 mmHg to 63.9 mmHg); intracranial pressure, however, remained within the normal range. All animals in Group 3 survived. Our findings indicate that elevated intracranial pressure and alcohol intoxication have a cumulative or potentiating effect on depression of the respiratory centre. Respiratory depression can be prevented by mechanical ventilation and, therefore, a further rise of intracranial pressure can be generally avoided. PMID- 3101535 TI - [Effectiveness of the benzodiazepine antagonist Ro 15-1788 following anesthesia induced by flunitrazepam]. AB - The competitive benzodiazepine antagonist Ro 15-1788 proved efficacious after general anaesthesia induced by flunitrazepam. It showed a quick onset of action within 1-2 min. After antagonisation, the heart rate, blood pressure and respiratory rate remained stable. No increased demand for analgesics could be demonstrated postoperatively. A transient anxiety that could be observed in 7 of 38 patients after doses between 0.5 and 2.0 mg seemed of minor clinical importance but may indicate that Ro 15-1788 acted not only as a pure antagonist but as a partially inverse agonist as well. Recurrence of sedation could be observed in 6 out of 38 patients after 2 h of Ro 15-1788 dosage. Careful observation of the patients for at least 2 h is therefore recommended even if antagonisation seemed successful. It was possible to reverse the benzodiazepine action successfully with doses between 0.3 and 0.8 mg. After these doses the patients will awake gently and gradually and unwanted side effects will be avoided. In our experience, Ro 15-1788 is a useful improvement in benzodiazepine application after surgical anaesthesia. PMID- 3101537 TI - Benzodiazepine antagonist Ro 15-1788. Antagonism of diazepam sedation in outpatients undergoing gastroscopy. AB - In a double-blind, randomised trial the efficacy and safety of Ro 15-1788, a new benzodiazepine antagonist, was assessed in forty adults undergoing gastroscopy under diazepam sedation. Criteria of efficacy were the degree of sedation and anterograde amnesia. There was a significantly faster recovery of the patients after the injection of 0.6-1.0 mg of Ro 15-1788 than after placebo. Patients were awake shortly after Ro 15-1788, but remained drowsy or asleep after placebo administration. There were no side effects of note. PMID- 3101538 TI - Respiratory disturbance and posterior fossa surgery. A case report. AB - This report, of a 16-month-old child recovering from surgery for a posterior fossa tumour, illustrates how pneumotachography, capnography and occlusion testing before and during CO2 challenge can be of clinical value in the analysis of a difficult respiratory disturbance in the early postoperative period. The application of these techniques to assist decisions regarding timing of extubation as well as for assessment of the influence of remaining tumour on respiratory competence is discussed. PMID- 3101539 TI - Single breath end-tidal PCO2 measurement during high frequency jet ventilation in critical care patients. AB - The relationship between arterial and end-tidal carbon dioxide tensions following a single large breath was investigated in seven critically ill patients receiving high frequency jet ventilation. There was a close correlation (r = 0.989) between arterial and end-tidal carbon dioxide tensions over a wide range (3.29-8.95 kPa). Measurement of the end-tidal carbon dioxide tension following a single large breath may be useful in monitoring the efficiency of high frequency jet ventilation in the elimination of carbon dioxide. PMID- 3101540 TI - Bain anaesthetic system and gender. PMID- 3101541 TI - Determination of stereochemistry in the fatty acid hydroperoxide products of lipoxygenase catalysis. AB - High-performance liquid chromatography has been found to be an effective method for the determination of absolute configuration in the products of the lipoxygenase-catalyzed oxygenation of polyunsaturated fatty acids. Methyl esters of fatty acid hydroperoxides that had been reduced to the corresponding alcohols were converted into (+)-alpha-methoxy-alpha-trifluoromethylphenylacetic acid esters. Enantiomeric alcohols were converted into diastereomeric esters that were readily resolved by normal-phase HPLC. The instrumental requirements for the technique are an isocratic HPLC and a uv absorbance monitor. The method was found to be effective in the determination of stereochemistry in the products derived from the action of plant lipoxygenases on linoleic acid. In addition, the chromatography of the derivatives obtained from lipoxygenase catalysis on arachidonic acid was found to be effective for the assignment of stereochemistry in those products. A comparison of the chromatography of these derivatives with that for the corresponding menthyloxycarbonyl derivatives demonstrated the superiority of this approach for the resolution of the diastereomeric pairs. The technique was applied to the determination of stereochemistry in the products derived from soybean lipoxygenase isoenzymes under a variety of experimental conditions. PMID- 3101542 TI - Isolation of 3,4-dihydroxyphenylalanine-containing proteins using boronate affinity chromatography. AB - A rapid procedure for the isolation of 3,4-dihydroxyphenylalanine-containing proteins has been developed in which the protein is selectively bound to a m phenylboronate agarose column, and eluted with 1.0 M ammonium acetate, pH 3.0. The method is based on the affinity of boronates for diols including catechol. The chromatography is carried out in the absence of oxygen to prevent oxidation of the catechol. Other proteins are eluted beforehand with 0.25 M ammonium acetate, pH 8.5, or for glycoproteins with a Tris buffer containing 0.2 M sorbitol, pH 8.5. PMID- 3101544 TI - Rapid structure elucidation of catecholamine conjugates with tandem mass spectrometry. PMID- 3101543 TI - A general assay for UDPglucuronosyltransferase activity using polar amino-cyano stationary phase HPLC and UDP[U-14C]glucuronic acid. AB - The assay of UDPglucuronosyltransferase activity toward various substrates using UDP[U-14C]glucuronic acid is described. HPLC on a polar amino-cyano bonded phase column was used to separate radioactive glucuronides from unmetabolized UDP[U 14C]glucuronic acid and other labeled reaction products. Radioactivity was measured using flow-through scintillation counting. All the glucuronides analyzed, with one exception, chromatographed with the same retention time (9.0 9.6 min) under the conditions described. Glucuronide conjugates were identified by comparison with retention times of commercial glucuronide standards, using radioactive aglycones, or hydrolysis with beta-glucuronidase. The method provides a unified, sensitive (100-200 pmol of glucuronide product) and reproducible assay for a wide variety of UDPglucuronosyltransferase substrates, and could be extended to include many others. PMID- 3101545 TI - Application of glutaraldehyde to amperometric determination of protein in dairy products. PMID- 3101546 TI - [Results of low-dose treatment of oligozoospermia with clomiphene citrate]. AB - 30 oligozoospermia patients from the andrologic outpatient service of the University-Hospital for Gynecology and Obstetrics, Graz, Austria, received a treatment with clomiphene-citrate. A doses of 25 mg daily was given for 25 days, followed by a break of 5 days. This treatment cycle was repeated three times, providing a total of 4 months of therapy. Rigid criteria of selection were applied for the patients in this trial, pretreatment serum levels of FSH, LH, testosterone, prolactin and estradiol had to be in normal or low-normal range. After treatment FSH, LH and testosterone were re-evaluated and a semen analysis was performed. Six to eight weeks afterwards another spermiogram was done. A significant raise of sperm density was observed immediately after treatment and at the control 6-8 weeks after therapy. Motility and morphologic quality remained unchanged after the therapeutic course. Fructose content of seminal plasma raised significantly 6-8 weeks after therapy. FSH, LH and testosterone increased also on a significant level. 6 pregnancies could be achieved, no negative side effects of treatment had to be registered. PMID- 3101548 TI - Capnogram artifact during high airway pressures caused by a water trap. PMID- 3101547 TI - Hormonal and seminal parameters in infertile men. AB - 500 infertile patients (250 with and 250 without left side varicocele) and 33 fertile men were evaluated as far as seminal parameters and the hormonal status were concerned. Sperm motility was constantly lower in infertile patients also when infertile group was compared to fertile one with the same sperm density. Serum testosterone levels were lower in infertile groups when compared to fertile men, and this confirms the existence of an androgenic deficit as a common finding in infertility associated or not to varicocele. FSH and LH increased (p less than 0.001) when sperm density dropped to less than 5 X 10(6) spermatozoa/ml. A negative correlation was found between both gonadotropins and sperm count (p less than 0.001), also after exclusion of azoo- and oligozoospermic (less than 5 X 10(6) spermatozoa/ml) patients (p less than 0.01). Gonadotropins were moreover tightly correlated between each other (p less than 0.001). Our data suggest that both gonadotropins are tightly tuned with sperm output and thus with the spermatogenic potential. PMID- 3101549 TI - Respiratory interactions of ketamine and morphine. AB - Six healthy, consenting volunteer males received ketamine iv in five logarithmically scaled doses totaling 3 mg/kg on three occasions each. The sessions differed only in the initial injection of an unknown drug: placebo, morphine sulfate 0.2 mg/kg, or morphine sulfate 0.4 mg/kg. Initial and terminal steady-state ventilatory responses to CO2 (VERCO2) and isohypercapnic ventilation (end-tidal CO2 49.8 +/- 2.4 mmHg) during drug administration assessed CO2 mediated ventilatory drive. Oxygen concentration of 40% ablated hypoxic drive contribution. Morphine caused a decrease of isohypercapnic ventilation (VE) of 8.2 +/- 1.2 l/min after 0.2 mg/kg. Doubling the dose to 0.4 mg/kg gave a further depression of 6.6 +/- 1.8 l/min. No subject lost consciouness after morphine. Over a dose range of 0.39 to 3.0 mg/kg ketamine caused log-linear dose-related depression of 1.6 +/- 0.3 l/min for each doubling of dose, although the first significant depression of 4.9 +/- 1.1 l/min did not occur until the third dose (1.1 mg/kg) in the absence of morphine. All subjects were unconscious after 1.8 mg/kg ketamine. Slopes of the VERCO2 did not differ from control, regardless of the pretreatment, placebo, or morphine in the two doses. Ketamine alone, 3.0 mg/kg, caused a displacement of VERCO2 of +2.0 +/- 1.2 mmHg in CO2, while combination of ketamine and morphine in either dose caused a +10 mmHg displacement of VERCO2. Thus, ketamine appears qualitatively similar but less potent than premedicant doses of morphine in depressing respiration despite near equipotency in producing loss of consciousness. PMID- 3101550 TI - Relationship between invasive and noninvasive measurements of gas exchange in anesthetized infants and children. AB - Minute ventilation (VE), tidal volume (VT), carbon dioxide elimination (VCO2), and end-tidal (PETCO2) and arterial CO2 tensions (PaCO2) were measured in 39 anesthetized infants and children with body weights ranging from 3.1 to 31 kg. Eighteen children had normal cardiopulmonary function, seven had acyanotic congenital heart disease, and 11 had cyanotic congenital heart disease. One child had left heart failure and pulmonary congestion, and two had severe parenchymal lung disease. To evaluate differences between pulmonary gas exchange calculated from PaCO2 versus PETCO2, dead space volume (VD) and alveolar ventilation (VA) based on a PaCO2 (VDa, VAa) as well as on PETCO2 (VDET, VAET) were performed, and correlations between PaCO2-PETCO2, VDa/VT-VDET/VT, and VAa-VAET were carried out. It was demonstrated that in normal children, as well as in those with acyanotic congenital heart disease, PETCO2 correlated closely with PaCO2 (r = 0.94, 0.98, respectively). In children with cyanotic congenital heart disease, however, correlation between PETCO2 and PaCO2 was relatively poor (r = 0.61). Mean values for PaCO2 were significantly higher than PETCO2 in the cyanotic children (P less than 0.01), resulting in significant underestimation of physiologic dead space (P less than 0.05) and significant overestimation of alveolar ventilation (P less than 0.01). In three patients with pulmonary disease, large differences between PaCO2 and PETCO2 were comparable with those observed in the children with cyanotic congenital heart disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101551 TI - [Intensive therapy of protein-energy deficiency at the cachexia stage]. PMID- 3101552 TI - Monitoring of tissue-pO2 for invasive diagnostics in angiology and vascular surgery. AB - Hypoxic and ischemic states are the main problem makers in angiology and vascular surgery. It is therefore suggestive to employ the technique of tissue-pO2 measurement for the verification and support of diagnostic and therapeutic measures. Two forms of registration are possible: continuous monitoring of partial oxygen pressures in eight different places and registration in the form of pO2-histograms, which represents a kind of "representative opinion poll" held in the tissue. The effects of a surgical intervention (endarterectomy, bypass operation) and the efficacy of blood flow-promoting drugs were studied in several series. In 9 patients the effect of the blood flow-promoting agent pentoxifylline (3,7-dimethyl-1-(5-oxohexyl)-xanthine) was studied. The pO2-histograms exhibited a shift to the right by an average of 7 mmHg after administration of this drug. Moreover, findings obtained with sodium nitroprusside and nitroglycerin during induced hypotension indicate that the continuous measuring of tissue-pO2 and recording of oxygen pressure distribution curves (pO2-histogram) provide the clinician with essential guidance data for the improvement of diagnostics and therapeutic control. PMID- 3101553 TI - Double-blind group comparative trial of sodium cromoglycate eye ointment and placebo in the treatment of allergic eye diseases. AB - Thirty-one patients with allergic eye diseases were treated three times daily for 4 weeks in a double-blind trial comparing sodium cromoglycate eye ointment with placebo. Patients' and clinician's assessment of symptoms and overall opinions of treatment showed sodium cromoglycate was significantly better than placebo and was well tolerated. PMID- 3101555 TI - [Prophylactic antibiotherapy in surgery]. PMID- 3101554 TI - [Hemodynamic effect of the clamping of the carotid in the surgically treated coronary patient]. AB - To determine both the incidence of myocardial ischaemia and haemodynamic response to carotid cross-clamping in coronary artery disease, 30 patients undergoing carotid endarterectomy were studied with a clear history of effort related disabling angina pectoris. Myocardial ischaemia was detected by a recording of lead CM5 of the electrocardiogram. A radial arterial and a thermodilution pulmonary catheter were inserted to obtain haemodynamic measurements before and after carotid cross-clamping and unclamping. Anaesthesia was induced with increments of thiopental, fentanyl 6 micrograms X kg-1 and pancuronium. Additional fentanyl (2 micrograms X kg-1) was injected before skin incision and before carotid cross-clamping. Carotid cross-clamping results in a significant increase in both mean arterial blood pressure and capillary wedge pressure. Two patients experienced myocardial ischaemia with ST segment depression during carotid cross-clamping. Nitroglycerin infusion led to the improvement of ST segment depression. When halothane was additionally administered to patients who developed hypertension in response to carotid cross-clamping, arterial blood pressure returned to normal value. These results indicate that carotid cross clamping increases determinants of myocardial oxygen demand and may cause myocardial ischaemia in patients suffering from angina pectoris. PMID- 3101556 TI - [French survey on anesthesia systems and peroperative respiratory monitoring equipment]. AB - A national inquiry has been carried out in France. It concerned the anaesthetic systems and respiratory monitoring equipment in use at the moment, as well as that wished for. The equipment in use was very stereotyped: an open system with a respirator, for the most volumetric, and with a safety O2/N2O mixer. Monitoring is carried out with the pressure gauges and the measure of expiratory volume; only two thirds of the equipment had an alarm. The O2 and CO2 analysers were little used. Expired CO2 monitoring was only carried out in teaching hospitals and in big centres. Apart from this, the equipment was independent of the hospital and the type of surgery carried out. As for anaesthetic systems, 53% of centres would like obtain open systems, 15% closed systems; 32% did not answer. This increase in number of closed systems is not significant. However, a very strong wish for respirators with flow rate control and safety O2/N2O mixers was observed, whilst the safety parameters of these mixers were open to discussion. Respiratory monitoring was not just confined to the mechanical aspects, as 65% of centres wished to monitor FIO2. The big centres and the teaching hospitals were interested by the expiratory CO2 monitoring. This inquiry showed the interest in respiratory safety in operating theatres. Further studies should confirm or not the increasing interest in closed systems. PMID- 3101557 TI - Rational ordering of serum electrolytes: development of clinical criteria. AB - The purpose of this study was to determine the frequency of electrolyte abnormalities in emergency department patients, to assess the proportion of these abnormalities affecting patient outcome, and to develop a set of clinical criteria to allow selective ordering of serum electrolytes. The ordering physicians completed questionnaires describing the clinical presentations of 1,031 patients on whom electrolytes were requested. For every patient with abnormal electrolyte values, the chart was reviewed to ascertain whether this was a clinically significant electrolyte abnormality (CSEA). The clinicians' responses to the questionnaires were used to construct a clinical criteria set predictive of CSEAs. Five hundred forty-five patients (52.9%) had one or more abnormal electrolytes, but only 161 patients (15.6%) had CSEAs. A set of ten clinical criteria detected 159 of 161 CSEAs (98.8% sensitivity) and would have avoided the ordering of electrolytes in 262 cases (29.9% specificity). At a cost to the patient of $20 per set of electrolytes ordered, detection of 159 CSEAs using the clinical criteria would cost $96.73 per CSEA detected. Detection of the additional two CSEAs by ordering electrolytes on all patients in the series would cost an additional $5,240. If the accuracy of these clinical criteria is confirmed in other settings, they may be useful guidelines for reducing laboratory charges without compromising patient care. PMID- 3101558 TI - von Willebrand factor abnormalities in primary pulmonary hypertension. AB - In primary pulmonary hypertension of recent clinical onset, pulmonary endothelial cells show injury. To characterize this phenomenon, we measured plasma von Willebrand factor (vWF) by immunologic and ristocetin cofactor assays in 6 patients with primary pulmonary hypertension, 17 patients with secondary pulmonary artery hypertension associated with congenital heart disease or cystic fibrosis, and 13 patients with congenital heart disease and normal pulmonary artery pressure. In selected cases, we also determined the vWF multimer pattern. In all 6 cases of primary pulmonary hypertension, the ristocetin cofactor activity was increased relative to the vWF antigen (vWF:Ag) concentration (a ratio of 2.55 +/- 0.36; normal range, 0.8 to 1.4); 4 of the 6 also had a similar and abnormal vWF multimer pattern--an increased proportion of the fastest moving bands. In the other 2, the multimer pattern was normal. Of the other 30 patients, a mild increase in ristocetin cofactor/vWF:Ag was seen in only 2 with secondary pulmonary hypertension and 1 with normal pulmonary artery pressure: these also had an abnormal vWF multimer pattern that was different from that observed in patients with primary pulmonary hypertension. The vWF abnormalities we describe in primary pulmonary hypertension offer a marker of the disease and could be helpful in understanding its pathogenesis. PMID- 3101559 TI - Diagnosis of nosocomial pneumonia in intubated, intensive care unit patients. AB - The clinical distinction between bacterial colonization of the tracheobronchial tree and nosocomial pneumonia is difficult, especially in intubated patients. We studied 51 intubated, intensive care unit patients prospectively by serial examinations of tracheal aspirates for elastin fibers, graded Gram's stains, and quantitative bacterial cultures in conjunction with clinical and radiologic observations in an attempt to develop criteria for the early detection of pulmonary infection. Patients with infection had new or progressive pulmonary infiltrates plus 1 of the following: positive blood culture results, radiographic evidence of cavitation, or histologic evidence of pneumonia, or 2 or more of the following: new fever, new leukocytosis, or grossly purulent tracheal aspirates. Twenty-one patients developed infection, 22 remained colonized, and 8 had an uncertain status. Infiltrates developed in 34 patients (21 infected, 8 colonized, 5 uncertain status). Gram-negative bacilli were most commonly isolated and were more frequent in infected patients (81 versus 47%, p less than 0.05); Pseudomonas aeruginosa and Serratia marcescens were most often associated with infection. No differences were observed between infected and colonized patients in demographic features, smoking history, underlying disease, previous antibiotic therapy, days in hospital before intubation, preexisting pneumonia upon intubation, or highest temperature or leukocyte count during course. By univariate analysis, infected patients had a longer duration of intubation (p less than 0.05), higher Gram's stain grading for neutrophils (p less than 0.05) or bacteria (p less than 0.005), higher bacterial colony counts (p less than 0.05), and more frequent detection of elastin fibers in tracheal aspirates (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101560 TI - The inhibition of sulphur dioxide-induced bronchoconstriction in asthmatic subjects by cromolyn is dose dependent. PMID- 3101561 TI - The effect of rhamnolipid hemolysin of Pseudomonas aeruginosa on respiratory epithelium. PMID- 3101562 TI - Triple lumen catheters. Technological advance or setback? AB - Multilumen central venous catheters are commonly used in hospitalized patients. This study evaluated the incidence of bacterial or fungal growth from the tips of 119 catheters removed for mechanical failure, no longer needed, or suspected catheter sepsis. Results showed an overall catheter contamination (less than 15 colonies) rate of 23.5 per cent and an overall catheter infection (greater than 15 colonies) rate of 14.3 per cent. Use of these catheters for delivering nutritional support solutions should be minimized or avoided. PMID- 3101563 TI - Thrombolysis in the treatment of acute transmural myocardial infarction. AB - Since 1980, many data have been published concerning the pathophysiology of acute myocardial infarction and its effect on mortality. Research has been directed at developing a means of interrupting the evolution of transmural infarction and normalizing blood flow through the infarct-related vessel. Intracoronary delivery of thrombolytic agents has proved to be an effective, albeit logistically limited, means of reperfusion. The use of intravenous agents has broadened the applicability of thrombolytic therapy without severely compromising its efficacy. The recent availability of clot-selective agents has produced the potential of safely interrupting the infarction process at the earliest possible moment. This article reviews the research that has led to our use of thrombolytic agents and proposes a reasonable program of patient management in acute myocardial infarction. PMID- 3101564 TI - [Thromboembolic disease and anomalies of fibrinolysis]. AB - Quantitative abnormalities of fibrinolytic system factors (tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PA-inhibitor) are often found in the patients exhibiting an idiopathic thromboembolic pathology. Exploration of fibrinolytic system is performed by taking blood samples prior and after stimulation (after venous occlusion or DDAVP injection). Patients can be "good responders" (that is presenting with an increase of fibrinolytic activity after stimulation) or "bad responders". Among these latter (that is 30 p. 100 of cases), there are two groups: patients exhibiting an increase of PA inhibitor level, this concealing fibrinolytic role of t-PA released by stimulation (20 p. 100 of cases), patients failing to present any t-PA release through endothelial cells stimulation (10 p. 100 of cases). Furthermore, an hypofibrinolysis was demonstrated a long time ago, in certain thrombogenic conditions (post-operative period, obesity, elderly patients). Hypofibrinolysis was recently demonstrated, according to such conditions, as liable to an increase in the PA inhibitor levels. As pathogenic role of hypofibrinolysis is then demonstrated, therapeutic studies reducing the PA inhibitor level or increasing the t-PA rate produced and released by endothelial cells are to be developed. PMID- 3101565 TI - [Lupus-type anticoagulants and thromboses]. AB - The presence of a lupus circulating anticoagulant factor is recognised by prolongation of the coagulation time of certain tests such as the activated cephalin time and Quick's test: this abnormality is not corrected by adding plasma and is not associated with a deficit of any of the factors of coagulation. This is a common abnormality not only in patients with disseminated lupus erythematosis but also in other conditions, and it may also be observed in healthy subjects. This abnormality is often associated with thromboembolic complications although it is not possible to demonstrate a cause and effect relationship. PMID- 3101566 TI - [Septo-optic dysplasia disclosed in adults]. AB - A case of septo-optic dysplasia, presenting with focal epileptic fits in a 29 year old man, is described. Gas encephalography and CT scan demonstrated the main features of the malformation: a single ventricle overhanging a narrowed third ventricle, abnormal mass in the basal forebrain corresponding to an embryonic cyst, optic atrophy. Angiography revealed deep venous anomalies, and, in particular, absence or hypoplasia of the sinus recti. PMID- 3101567 TI - [Regression of IgA kappa monoclonal gammopathy in IgA lambda Kahler's disease]. AB - The authors report the case of a patient with a stable IgA kappa gammapathy over several years which finally evolved to an IgA lambda myeloma during which the initial gammapathy regressed. As the two gammapathies probably arose from two different cellular populations, the regression of the IgA kappa dysglobulinaemia is an additional argument in favour of the hypothesis that benign monoclonal gammapathies are the result of cellular hyperplasia. PMID- 3101568 TI - Anion transport in astrocytes. AB - We have examined the question of anion-transport systems in glia using primary astrocyte cultures prepared from neonatal rat brains. These studies show that these cells have exchange or cotransport systems for Cl- that appear to be electrically neutral, that is, SITS-sensitive Cl-/Cl- or Cl-/HCO3- anion exchange, and furosemide- and bumetanide-sensitive Na+ + K+ + 2Cl- cotransport. These inhibitors inhibit a major component of the total 36Cl- flux and the remaining Cl- flux may be conductive; however, this conductive flux makes a small contribution to Em relative to K+, since large changes in [Cl-]o do not usually affect Em, which is predominantly a K+ diffusion potential. We have also found an alpha-receptor-mediated depolarization that is affected by imposed changes in Ecl. The alpha-receptor-mediated depolarization seen at normal [Cl-]o could be partially due to increased Cl- conductance because [Cl-]i appears to be several fold higher than it would be if it were in equilibrium with the membrane potential. PMID- 3101569 TI - Double pharyngeal pouch. PMID- 3101570 TI - Management of plexiform neurofibroma of the larynx. AB - We report the ninth case of plexiform neurofibroma of the larynx, which occurred in a 2-year-old with multiple cafe au lait spots and obstructive sleep apnea. In discussing this clinical problem, we have attempted to make the following points. A patient's having more than six cafe au lait spots of greater than 1.5-cm diameter is diagnostic of von Recklinghausen's disease. It is much more difficult to completely excise plexiform neurofibroma than nonplexiform neurofibroma. The association of juvenile xanthogranuloma with von Recklinghausen's disease may be a risk factor for the later development of leukemia. PMID- 3101571 TI - International cochlear implant symposium and workshop--Melbourne, 1985. Papers and abstracts. PMID- 3101572 TI - [Influence of the number of inoculated parasites on the in vitro infestation of HeLa cells by the coccidia Besnoitia jellisoni Frenkel]. AB - The influence of the number of bradyzoites of the Coccidia Besnoitia inoculated in the culture medium of HeLa cells on their penetration rate was investigated. The intracellular penetration rate increased with the "size of inoculum", then seemed constant when a certain density is reached. Important densities of bradyzoites in the inoculum led to an unequal distribution of intracellular parasites among the cellular sheet. Multiple infective units in a same host cell did not occur randomly. It seems that some cells are more suitable than others to parasite invasion. PMID- 3101573 TI - [Immunofluorescent reaction of antibodies directed against antigens from the intestinal epithelium of Schistosoma mansoni. III. Study of the reactivity of monoclonal antibodies]. AB - A monoclonal mouse antibody of IgM class was raised against an epitope of the gut epithelium of the adult worm and was applied to the detection of antigen in parasite infection. The antigen was found in urine from mice and hamsters infected with Schistosoma mansoni; a good correlation between the concentration of antigen and worm burden was observed. The antigen was thermostable, soluble in trichloracetic acid; it was not hydrolysed by proteinase K but it was destroyed by metaperiodate. The antigen was shown to be Schistosoma genus specific. It was found in different developmental stages of the parasite. High levels were detected in egg extracts. PMID- 3101574 TI - [Malignant pheochromocytoma associated with Recklinghausen's disease. Apropos of a case. Value of new methods in the diagnosis of pheochromocytoma]. AB - After having reported the case of a pheochromocytoma associated to Recklinghausen's disease, the authors define the best criteria of detection and localization of the pheochromocytoma and study its association to phacomatoses. Headaches, bouts of tachycardia and excessive inappropriate diuresis are the most evocative clinical signs of a pheochromocytoma. The different hormones and their urinary metabolites must be titrated separately and repeatedly. Two other examinations, scanner and scintigraphy with MIBG, visualize quite reliably the tumor foci. Calcium inhibitors are quite effective in sudden blood pressure rises. The association described here, may be explained by the fact that the two pathologies belong to the group of neurocristopathies. PMID- 3101575 TI - Early clinical signs and prognosis in children with brain injuries. AB - The outcome of 76 brain-injured children treated at the Department of Neurosurgery, Kuopio University Central Hospital, Kuopio, Finland, during 1980-83 was analyzed to determine the prognostic value of early clinical signs and investigations. Five (8%) of the children died. The coma level (Glasgow Coma Score, GCS) was below 9 in 24 children, four (17%) of whom died. Three of these deaths occurred very early, during or soon after the computerized tomography (CT) study and in these cases aggressive treatment was withheld. There were actually no deaths in children with GCS of 6-8 and one death due to severe intra-abdominal injury in 52 children with GCS of 9-14. Seventeen (22%) of the children had multiple injuries. Fourteen children had significant intracranial hematoma or depressed skull fracture requiring surgical treatment, and all of these children did well. The intraventricular pressure was measured in 11 children with GCS of 3 5, all under controlled respiration. Six children had increased intracranial pressure (ICP), above 20 mmHg. In one child the pressure could not be managed, and she died. CT gave very important prognostic information. All children who died of early uncontrollable ICP already had marked hemorrhagic lesions in the basal cisterns, hypodense areas in the brain stem or brain stem compression. Early and repeated CT to show the complications and aggressive intensive care with intracranial pressure recording in children with GCS of 3-5 can keep the mortality associated with severe brain injury below 20% with an acceptable level of survival. PMID- 3101576 TI - Food restriction inhibits [3H] 7,12-dimethylbenz(a)anthracene binding to mouse skin DNA and tetradecanoylphorbol-13-acetate stimulation of epidermal [3H] thymidine incorporation. AB - It has been known for many years that reducing the food intake of laboratory mice and rats inhibits the development of a broad spectrum of chemically induced and spontaneous tumors, but the mechanism of this effect is poorly understood. Food restriction of A/J mice for two weeks is now shown to inhibit the binding of topically applied [3H]7,12-dimethylbenz(a)anthracene (DMBA) to skin DNA by 50% and to abolish the stimulation of [3H]-thymidine incorporation in the epidermis produced by topical application of the tumor promoter tetradecanoylphorbol-13 acetate (TPA). Similar effects on the actions of DMBA and TPA are observed following topical application of the adrenal steroid, dehydroepiandrosterone (DHEA), a potent glucose-6-phosphate dehydrogenase (G6PDH) inhibitor, while food restriction for two weeks depresses epidermal G6PDH activity by 60%. It is suggested that both the inhibition of [3H]DMBA binding to skin DNA and the TPA stimulation in epidermal [3H]thymidine incorporation result from a reduction in the NADPH cellular pool as a result of G6PDH inhibition. PMID- 3101577 TI - Identification of cell types in human melanoma cultures using a panel of morphological, cytochemical and immunological tests. AB - Although it is well known that fibroblasts can overgrow melanoma cells in culture during early passaging, some investigators have claimed recently that these fibroblast-like cells are actually melanocytes de-differentiated in vitro. In order to test these claims, we examined 27 melanoma-derived cell lines using anti melanoma and anti-fibroblast monoclonal antibodies, the dioxyphenylalanine cytochemical reaction specific for melanocytes, the leucine aminopeptidase cytochemical reaction for fibroblast cells, and chromosomal analysis. All these assays - which discriminate melanomas from fibroblasts - confirmed our initial classification by morphology, namely that thirteen of the lines were melanocytic and twelve were fibroblastic, while the remaining two were a mixture of the two cell types. There was no indication of a mixed phenotype which would have been the result of some transaction in the state of differentiation. Our results suggest that the 27 cell lines and cultures are composed of pure melanocytic populations, or are fibroblasts as a result of fibroblast overgrowth. The two cultures containing a mixed cell population are those in which one cell type has not overtaken the other. There is no evidence to support the idea that some true melanoma cultures have the morphology of fibroblast-like cells. PMID- 3101579 TI - Prolactin in partial epilepsy: an indicator of limbic seizures. AB - A study was performed to evaluate changes in serum prolactin levels after simple and complex partial seizures, and to identify which specific anatomical structures must be involved in seizures for postictal elevation of prolactin levels to occur. Seventy-eight seizures were studied in patients with electrodes implanted bilaterally into amygdala, hippocampus, hippocampal gyrus, and frontal sites. All 38 complex partial seizures had bilateral limbic ictal discharges, and each was followed by a significant increase in prolactin concentration (mean peak, 50.8 ng/ml; range, 16.0 to 150.0 ng/ml). Eight of 10 simple partial seizures with unilateral high-frequency regional limbic discharges were followed by prolactin elevation (mean peak, 28.2 ng/ml; range, 13.4 to 44 ng/ml). Thirty simple partial seizures with other ictal limbic discharges or without limbic discharges were not followed by an elevated prolactin level. The data indicate that serum prolactin levels always rise after complex partial seizures involving the temporal lobes, and rise after certain simple partial seizures involving limbic structures. Thus, measurement of the prolactin level can help identify which simple partial seizures involve mesial temporal lobe structures. Limbic structures serve to trigger prolactin release, which may depend upon spread of the seizure to subcortical structures. PMID- 3101578 TI - Suppression by pregnancy of chemically induced preneoplastic cells of the rat mammary gland. AB - Since a previous study suggested that pregnancy either eliminated preneoplastic cells or increased their latency period in rat mammary glands, additional experiments were performed to determine the fate of these cells. Following administration of the carcinogen dimethylbenzanthracene, few mammary cancers appeared after rats completed pregnancy and lactation. Because these results are similar to those previously obtained with N-methyl-N-nitrosourea (MNU), the effect of pregnancy appears to be independent of the carcinogen used to induce cancer. For rats dosed with MNU, relatively few cancers developed either during an extended observation following pregnancy and lactation or following administration of prolactin, a growth stimulator of mammary cancers. In the latter experiment, the average number of mammary cancers per rat in the prolactin treated virgin rats was 7.1, while prolactin-treated parous rats had only 0.8 cancers per rat; i.e., 89% fewer cancers. Thus, pregnancy appears to suppress many of the preneoplastic cells induced by carcinogens in the mammary gland of rats. PMID- 3101580 TI - Changes in epileptic spike configuration associated with attainment of seizure control. AB - This study provides preliminary evidence that computer-derived parameters of interictal spike waveforms can be used to assess seizure hazard in a quantitative manner. Thirteen children with spike foci and simple or complex partial seizures were studied before and during treatment with carbamazepine or phenobarbital; spike parameters were determined from 5- to 30-minute electroencephalographic samples obtained during non-rapid eye movement sleep. Measurements included spike amplitude, duration, and sharpness, and a mathematical combination of these three parameters (the composite spike parameter). Achievement of seizure control was associated with a decrease in spike amplitude, duration, and composite spike parameter, and an increase in normalized sharpness, compared to baseline values. These results suggest that this method may provide a prospective means for estimating drug efficacy that can be applied shortly after attainment of steady state serum drug levels. PMID- 3101581 TI - Decontamination of Creutzfeldt-Jakob disease agent. PMID- 3101582 TI - Genomic reorganization in ciliated protozoans. PMID- 3101583 TI - Genetics of endospore formation in Bacillus subtilis. PMID- 3101584 TI - [Selective agents for isolating Pseudomonas aeruginosa]. PMID- 3101585 TI - [Nisin biosynthesis during the joint cultivation of Streptococcus lactis strain MGU and yeasts]. AB - In simultaneous inoculation of the medium for nisin biosynthesis with Streptococcus lactis (strain MSU) and yeasts such as Rhodotorula colostri, Zigowilliopsis californicus, Hansenuia anomala, Saccharomyces ludvigii, Kluyveromyces lactis and Endomyces magnusi the quantitative ratio of the inoculates in the mixed cultures is not in principle important for the antibiotic synthesis by the Streptococcus. When 6-, 12-, 18- and 24-hour inoculates of the yeasts were added simultaneously to 3-, 6-, 9-, 12- and 18-hour cultures of S. lactis biosynthesis of nisin was at the control level. The fractional composition of the fermentation broth of the above yeast species had no significant effect on biosynthesis of nisin. PMID- 3101586 TI - Evaluation of a radiometric method for pyrazinamide susceptibility testing of Mycobacterium tuberculosis. AB - Pyrazinamide susceptibility testing of Mycobacterium tuberculosis requires an acid environment. By controlling the method of acidification and the quality and quantity of the inoculum, the test can be performed with the BACTEC radiometric system (Johnston Laboratories, Towson, Md.). We acidified BACTEC 7H12 medium with buffered phosphoric acid and adjusted the test inoculum to 1/10 of that usually employed in BACTEC protocols; after 5 days of growth we correctly identified 36 of 36 strains susceptible to 50 micrograms of pyrazinamide per ml. All 18 resistant strains were classified as pyrazinamide resistant. (Susceptibility or resistance had been determined by standard plate assays.) The test was able to detect small resistant populations in artificial mixtures of 1 or 2% resistant bacteria with a susceptible strain (10 mixtures each). We tested 70 M. tuberculosis strains in acidified BACTEC 7H12 medium and by the plate dilution test at pH 5.5. All strains grew in the BACTEC medium, but three strains failed to grow on plates and were not tested further; the results of both methods agreed for the remaining strains. PMID- 3101587 TI - Genetics of resistance in a non-beta-lactamase-producing gonococcus with relatively high-level penicillin resistance. AB - A penicillin-resistant (Penr) non-penicillinase-producing Neisseria gonorrhoeae strain responsible for an outbreak affecting 199 persons in Durham, N.C., in 1983 was studied to determine the genetic basis of its unusually high-level (MIC, 2.0 micrograms/ml) Penr. Plasmid screening of the strain revealed no plasmids other than the 2.6-megadalton cryptic plasmid. Penr was found to be partially due to mutations genotypically and phenotypically similar to the previously characterized chromosomal loci penA, mtr, and penB. Resistance loci from the epidemic donor strain were transformed into susceptible recipients FA19 and F62 in a stepwise fashion; the combination of the three loci resulted in moderate levels of penicillin resistance (MIC, 0.5 micrograms/ml), but donor levels of resistance were not obtainable in either recipient, for uncertain reasons. Occurrence of an antibiotic-susceptible (env) mutation in a clinical isolate of the Penr epidemic strain also was documented. PMID- 3101588 TI - Ethambutol MICs and MBCs for Mycobacterium avium complex and Mycobacterium tuberculosis. AB - We determined the MICs of ethambutol for both Mycobacterium avium and Mycobacterium tuberculosis strains by using broth dilution (7H12 broth, radiometric method) and agar dilution (7H11 agar) methods. We found the MICs to be much lower in liquid than in solid medium. The broth-determined MICs for susceptible M. tuberculosis and most of the M. avium strains were comparable to the levels in blood of patients, being lower than the peak levels. We propose that the MICs, determined radiometrically in in 7H12 broth, be considered as tentative criteria for susceptibility testing of M. avium isolates in future clinical trials. The use of these values instead of critical concentrations should also be considered as an alternative to the conventional susceptibility testing method in chemotherapy of tuberculosis. Ethambutol produced bactericidal effects against both M. tuberculosis and M. avium, and the MIC/MBC ratios were in the same range for both species when MICs and MBCs were tested in 7H12 broth by conventional sampling and plating. PMID- 3101589 TI - Activity of ciprofloxacin against multiply resistant strains of Pseudomonas aeruginosa, Staphylococcus epidermidis, and group JK corynebacteria. AB - The susceptibilities of multiply resistant clinical isolates of Pseudomonas aeurginosa to ciprofloxacin, norfloxacin, and several beta-lactam and aminoglycoside antibiotics were evaluated. Ciprofloxacin also was compared with methicillin and vancomycin against methicillin-resistant Staphylococcus epidermidis and group JK corynebacteria. Ciprofloxacin exhibited the lowest MICs and MBCs for 90% of the isolates among all of the antibiotics tested against P. aeruginosa. In addition, ciprofloxacin exhibited excellent bactericidal activity against the gram-positive organisms. Clinical trials are necessary to confirm the in vitro results and monitor for emergence of resistance. PMID- 3101590 TI - In vitro activity of A-56619 (difloxacin), A-56620, and other new quinolone antimicrobial agents against genital pathogens. AB - The in vitro activities of two new carboxyquinolones, A-56619 (difloxacin) and A 56620, were compared with those of ciprofloxacin, norfloxacin, and ofloxacin against genital tract pathogens. All the quinolones were highly active against Neisseria gonorrhoeae. A-56619 had the lowest MICs against Chlamydia trachomatis (MIC range, 0.125 to 0.25 micrograms/ml) and Haemophilus ducreyi (MIC for 90% of isolates tested, 0.1 micrograms/ml). PMID- 3101591 TI - Reversible inhibition of flagella formation after specific inhibition of spermidine synthesis by dicyclohexylamine in Pseudomonas aeruginosa. AB - Dicyclohexylamine, which is an inhibitor of bacterial and mammalian spermidine synthase, greatly inhibited the synthesis of spermidine in Pseudomonas aeruginosa. The depletion of spermidine caused by dicyclohexylamine was accompanied by an inhibition of growth of bacteria. This inhibition was reversed by addition of 50 microM spermidine (but not putrescine or spermine) to growth medium. When its growth was inhibited Ps. aeruginosa also lost its motility. Electron microscopy showed a loss of flagella in spermidine-deficient bacteria: after 24 h 70% 85% of bacteria grown in the presence of dicyclohexylamine did not have flagella, whereas bacteria grown in the presence of dicyclohexylamine and spermidine had flagella. The loss of flagella was reversible, since after the inhibition of spermidine synthesis for 24 h, addition of 50 microM spermidine (but not putrescine or spermine) to the growth medium was able to restore the bacterial motility almost completely after a further 12 h growth period. PMID- 3101592 TI - Oxygen limitation on L-serine production in a hollow-fiber bioreactor. AB - Pseudomonas AM1 utilizes glycine and methanol to produce L-serine aerobically. The consumption of methanol in this bioconversion is stoichiometrically in excess of L-serine production. Consequently, the oxygen requirement associated with L serine production is higher than expected for the conversion from glycine. One method of L-serine production investigated was a technique utilizing a hollow fiber ultrafiltration cartridge as a bioreactor. Oxygen diffusion limitations appear to impede the consumption of methanol and, consequently, the production of L-serine in such a reactor. Methanol consumption data agree with predictions based on a hollow-fiber diffusion model. PMID- 3101593 TI - Calcium effects on calmodulin lysine reactivities. AB - The differential reactivities of individual lysines on porcine testicular calmodulin were determined by trace labeling with high specific activity [3H]acetic anhydride as a function of the molar ratio of Ca2+ to calmodulin. In progressing from the Ca2+-depleted form of the protein to a Ca2+:calmodulin molar ratio of 5:1, six of the seven lysyl residues exhibited a modest 1.5- to 3.0-fold increase in reactivity. Lys 75, in contrast, was enhanced in reactivity greater than 20-fold. When the change in reactivity of each lysine was normalized as a percentage of the maximum change, most of the residues were found to fall into two distinct classes. One class, comprising lysines 94 and 148 from the two carboxy terminal Ca2+-binding domains 3 and 4, respectively, exhibited about 90% of their reactivity change when the Ca2+:calmodulin molar ratio was 2:1, and these residues were perturbed very little upon further addition of Ca2+. The other class, encompassing lysines 13, 21, and 30 from the amino terminal domain 1 and Lys 75 from the extended helix connecting the two globular lobes of calmodulin, underwent most of their overall reactivity change (55-70%) between 2 and 5 equivalents of Ca2+ per mol of calmodulin. Lys 77 was distinct in its pattern of change, undergoing approximately equal changes with each Ca2+ increment. These results are consistent with a model where Ca2+ first binds to the two carboxy terminal sites of calmodulin with no apparent preference, concomitant with minor alterations in the microenvironments of lysines in the unoccupied amino terminal domains. The third and fourth Ca2+ ions then bind to these latter two domains, again with no evidence of preference, with little change in the lysine reactivities at the carboxy terminus of the molecule. The environments of groups in the central helix appear to undergo changes in a manner that reflects their proximity to the amino and carboxy terminal domains. In the course of this work, it was found that Lys 94 in apocalmodulin is specifically perturbed by the addition of EGTA, suggesting that the chelating agent may interact with calmodulin at or near the third Ca2+-binding domain. PMID- 3101594 TI - Characterization of beta-glucosidases with high specificity for the cyanogenic glucoside dhurrin in Sorghum bicolor (L.) moench seedlings. AB - Two beta-glucosidases exhibiting high specificity for the cyanogenic glucoside dhurrin have been purified to near homogeneity from seedlings of Sorghum bicolor. Dhurrinase 1 was isolated from shoots of seedlings grown in the dark. Dhurrinase 2 was isolated from the green shoots of young seedlings grown in the light. The two enzymes were similar in following characteristics: their optimum activity is around pH 6.2; the enzymes are stable above pH 7; they are effectively inhibited by the beta-glycosidase inhibitors nojirimycin delta-gluconolactone and 1-amino beta-D-glucoside. On the other hand, they clearly differed in other properties, e.g., molecular weights, isoelectric points, and substrate specificity. Moreover, dithiothreitol has no effect on dhurrinase 1, but is necessary for the activity of dhurrinase 2. Preliminary investigations indicate that the two enzymes are located in different parts of the sorghum seedlings: dhurrinase 1 is found in the coleoptiles and hypocotyls; dhurrinase 2 occurs in the leaves. Dhurrin (p-hydroxy (S)-mandelonitrile-beta-D-glucoside) and its structural analog without the hydroxyl group, sambunigrin, were the only substrates hydrolyzed at high rate, the Km values with both enzymes being 0.15 and 0.3 mM, respectively. All other cyanogenic glucosides tested, as well as synthetic substrates such as 4 nitrophenyl-beta-D-glucoside, were in general poor substrates, especially for dhurrinase 1, the enzyme isolated from coleoptile and hypocotyl tissue. Dhurrinase 1 appears to exist within the seedlings as a tetramer (Mr - 2-2.4 X 10(5)) which dissociates without loss of activity into a dimeric form (Mr = 1-1.1 X 10(5)) upon extraction and purification. There is only one monomeric subunit with Mr = 5.7 X 10(4). Isolectric focusing and chromatofocusing of purified dhurrinase 1 showed the presence of at least three isomeric forms, but their relationship to each other is not known at the present time. Dhurrinase 2 appears to be a tetrameric protein with Mr = 2.5-3 X 10(5); it also has only one monomeric subunit of Mr = 6.1 X 10(4). In contrast to many other beta glucosidases, the dhurrinases are not glycoproteins. PMID- 3101595 TI - Oxidation of esterified arachidonate by rat liver microsomes. AB - Rat hepatic microsomal lipids were labeled with [U-14C]arachidonate and were then peroxidized by an NADPH-dependent iron pyrophosphate system. The extent of peroxidation was quantified by malondialdehyde production and arachidonate disappearance. Following peroxidation, the microsomes were centrifuged and the oxidation products were extracted from the supernatant. A linear correlation was found between malondialdehyde production and radioactivity in the supernatant. The pellet was treated with phospholipase A2 to cleave peroxidized products from the phospholipids. Exogenous phospholipase A2 activity was reduced by lipid peroxidation but this was overcome by using a high concentration of the enzyme along with the addition of melittin. The deesterified lipid products from the pellet were extracted and the fragments from the supernatant and the hydrolyzed pellet were separated by reverse-phase HPLC. Several different labeled polar products which coeluted with carbonyl-containing compounds (A285 and hydrazone formation) were found in both the supernatant and the pellet. In addition, many other carbonyl compounds were found which were not arachidonate-derived. The elution pattern of the fragments after 2 and 15 min of peroxidation were qualitatively identical; i.e., no product-precursor relationship was seen. This, along with the observation that peroxidation quickly ceased upon the rapid depletion of NADPH, suggests that propagation did not occur. Finally, the data indicate that cytochrome P-450 is not involved in microsomal lipid peroxidation since product formation is unaffected by the presence of carbon monoxide (80%) and no oxidation of phospholipid arachidonate occurs in the absence of iron. PMID- 3101596 TI - Some unique features of the metabolic conversion of platelet-activating factor (AGEPC) to alkyl acyl PC by washed rabbit platelets. AB - Recently several synthetic analogs of 1-0-alkyl-2-acetyl-sn-glycero-3 phosphocholine (AGEPC; platelet-activating factor) were characterized as selective inhibitors of this agonist's effects on rabbit platelets (Tokumura, A., Homma, H., and Hanahan, D. J. (1985) J. Biol. Chem. 260, 12710-12714). In this current investigation, these studies have been extended to include a further inquiry into the biochemical nature of the metabolic inactivation of AGEPC in rabbit platelets, and the effect of these analogs on this process. Two of the latter components (U66985 and CV3988), which blocked AGEPC biological activity on rabbit platelets, also blocked the metabolism of this agonist. The metabolic conversion of AGEPC to alkyl acyl PC was inhibited nearly sevenfold by the most potent analog, U66985. Those analogs with low (U68043) or no biological inhibitory activity (lysoGEPC) had marginal effects on the metabolism of AGEPC. The effects of these compounds on the metabolism of AGEPC was not simply due to competitive inhibition. In platelets which had been pretreated with AGEPC in absence of extracellular Ca2+ (desensitized) and washed, the metabolic conversion of AGEPC to alkyl acyl PC was actually enhanced. This enhanced metabolic inactivation of AGEPC was also observed upon the treatment of the cells with thrombin, collagen, or ionophore A23187, indicating that the metabolism of AGEPC in platelets was enhanced not only by AGEPC itself but by other agonists as well. Nearly 85% of the fatty acyl residues was arachidonate in the alkyl acyl PC derived from AGEPC. This specific acylation with arachidonate was observed in the presence and absence of the inhibitor and in desensitized cells, indicating that selectivity for arachidonate is not dependent on the enhancement of the metabolism of AGEPC. The alkyl acyl PC found in the cells treated with thrombin, collagen, or A23187 was also predominantly alkyl arachidonoyl PC. Thus it has been shown that the inactivation of AGEPC by its conversion to alkyl acyl PC by rabbit platelets is enhanced by this agonist itself and that excess amounts of AGEPC could be further inactivated by the enhanced capacity of the metabolism process. PMID- 3101597 TI - The pressure-induced inactivation of mammalian enolases is accompanied by dissociation of the dimeric enzyme. AB - The effects of exposure to pressure on both the activity and the quaternary structure of rabbit brain enolases, forms alpha alpha, alpha gamma, and gamma gamma were studied in the pressure range of 1 to 3400 bar. Effects on quaternary structure were determined by subunit scrambling (the formation of alpha alpha and gamma gamma from alpha gamma or vice versa). All three dimers are stable up to pressures of 1200 bar. The dissociation of gamma gamma begins at 1200 bar, yielding a stable monomer; inactivation of gamma gamma does not begin until the pressure is greater than 2000 bar. Dissociation of gamma gamma is not accompanied by changes in the tryptophan fluorescence of the protein. However, the fluorescence does decrease when the pressure is greater than 2000 bar, the point at which inactivation of gamma gamma starts. The alpha monomer, on the other hand, is unstable in the pressure range that produces dissociation of alpha alpha. This process, which also begins at 1200 bar, is paralleled by inactivation. Crosslinking the enzyme with glutaraldehyde demonstrated that the inactive form of the enzyme is monomeric. The pressure-induced inactivation of these forms of enolase is thus clearly a two-step process, with both dissociation and inactivation occurring. The difference in pressure sensitivity of rabbit brain alpha alpha and gamma gamma is due to a difference in stability of the alpha and gamma monomers and not due to a difference in the pressures required for dissociation. PMID- 3101598 TI - Phosphorylation of human fibrinogen in vitro with protein kinase C: characterization of the phosphorylated sites. AB - Phosphorylation of human fibrinogen in vitro by incubation with [gamma-32P]ATP and protein kinase C purified from pig spleen, led to incorporation of [32P]phosphate at serine residues located in the A alpha-chain. In order to identify the residues that were phosphorylated, the A alpha-chain of fibrinogen was isolated and subjected to consecutive cleavage by cyanogen bromide, trypsin, and chymotrypsin. The resulting radioactive phosphopeptides were purified by gel chromatography and high-performance liquid chromatography using a reversed-phase column. Subsequent amino acid analysis and manual Edman degradation of the purified phosphopeptides revealed that Ser557, Ser558, Ser559, and Ser599 were phosphorylated. These serine residues are located in the carboxy-terminal part of the A alpha-chain. This region also contains lysine residues participating in the cross-linking of fibrin and, possibly, a site involved in the binding of fibrinogen to receptors on platelets. In addition, peptides derived from the middle section of the polypeptide chain were found to contain [32P]phosphate; in these cases, however, the exact localization of the phosphate could not be determined, due to the low yield of radioactivity. Two glutamine residues, Gln328 and Gln366, in this portion of the A alpha-chain take part in the cross-linking of fibrin. PMID- 3101599 TI - Characterization of highly purified dopamine beta-hydroxylase. AB - A modified purification procedure has been developed for dopamine beta hydroxylase isolated from bovine adrenal medulla. Catalase is included in the homogenization step starting with a suspension of either chromaffin granules or adrenal medulla tissue. With this precaution, the enzyme remains stable in the supernatant solution in preparation for the subsequent purification step involving concanavalin A-Sepharose chromatography. The homogeneous enzyme has a specific activity in the range of 60-70 mumol O2 consumed/min/mg. Using radiolabeled metal ion chelators, it was determined that several of the chelators remained tightly bound to the enzyme after removal of the copper leading to difficulties in establishing stoichiometry of enzyme-bound metal ions. PMID- 3101600 TI - Metabolism of NG,NG-and NG,N'G-dimethylarginine in rats. AB - The metabolic fates of NG,NG-and NG,N'G-dimethylarginines in rats were investigated isotopically and novel metabolites, alpha-keto-delta-(N,N dimethylguanidino)-and alpha-keto-delta-(N,N'-dimethylguanidino)valeric acids and gamma-(N,N-dimethylguanidino)-and gamma-(N,N'-dimethylguanidino)butyric acids were identified. In the case of the rats injected with NG,NG-dimethyl-L [1,2,3,4,5-14C]arginine, about 13% of the radioactivity was recovered in the first 12-h urine and was distributed in the following metabolites (relative ratios): unchanged NG,NG-dimethyl-L-arginine (35.2%), gamma-(N,N dimethylguanidino)butyric acid (18.4%), alpha-keto-delta-(N,N dimethylguanidino)valeric acid (16.4%), and N alpha-acetyl-NG,NG-dimethyl-L arginine (8.5%). The radioactivity retained in the tissues was found mainly in citrulline and was further distributed in ornithine, arginine, and glutamic acid and even in protein-bound arginine. In the case of NG,N'G-dimethyl-L-[1,2,3,4,5 14C]arginine-injected rats, about 75% of the radioactivity was excreted in the first 12-h urine and was recovered in the following metabolites (relative ratios): N alpha-acetyl-NG,N'G-dimethyl-L-arginine (48.4%), unchanged NG,N'G dimethyl-L-arginine (23.7%), alpha-keto-delta-(N,N'-dimethylguanidino)valeric acid (20.2%), and gamma-(N,N'-dimethylguanidino)butyric acid (9.6%). In the tissues, most of the radioactivity was associated with unchanged NG,N'G-dimethyl L-arginine. These findings show that both dimethylarginines are metabolized by a pathway forming the corresponding alpha-ketoacid analogs and the oxidatively decarboxylated products of the alpha-ketoacids in addition to the N alpha-acetyl conjugates identified previously (K. Sasaoka, T. Ogawa, and M. Kimoto (1982) Arch. Biochem. Biophys. 219, 454-458), and NG,NG-dimethyl-L-arginine is catabolized by an additional pathway leading to the formation of citrulline and its metabolically related amino acids. By considering their catabolism, an attempt to use urinary dimethylarginines as an index of in vivo breakdown of tissue proteins is invalid at least in rats. PMID- 3101601 TI - Photorespiration stoichiometry in leaves estimated by combined physical and stereochemical methods: allowance for isomerase-catalyzed 3H losses in ribulose bisphosphate regeneration. AB - We showed previously [K.R. Hanson and R.B. Peterson (1986) Arch. Biochem. Biophys. 246, 332-346] that under steady-state photosynthetic conditions the fraction of ribulose bisphosphate oxidized and the fraction of glycolate carbon photorespired (the stoichiometry of photorespiration) may be estimated in leaves by a combination of physical and stereochemical methods. The calculations assumed that when (3R)-D-[3-3H1,3-14C]glyceric acid is supplied to illuminated leaf discs the only loss of 3H from the combined photosynthetic and photorespiratory system is the result of glycolate oxidase action; i.e., the isomerase-catalyzed losses in the regeneration of ribulose bisphosphate are negligible. The present study of tobacco leaf discs under zero-photorespiration conditions (low O2 and high CO2 concentrations), and also of maize leaf discs, shows that some 3H losses occur (between 8 and 13% of the 3H at C-1 of ribulose 5-phosphate). The calculated loss varied moderately with temperature but did not vary when the flux of ribulose bisphosphate formation was altered by changing the irradiance. The calculated loss under zero-photorespiration conditions, therefore, may be used to calculate ribulose bisphosphate and glycolate partitioning under other conditions. Earlier experiments on the influence of O2 and CO2 concentrations of temperature on the partitioning of ribulose bisphosphate and glycolate have been reexamined. The loss corrections decreased all values for the fraction of ribulose bisphosphate oxidized and increased all values for the stoichiometry of photorespiration. Essentially all stoichiometry values were above the theoretical lower limit of 25%. The previous conclusion that the stoichiometry of photorespiration substantially exceeds 25% at higher O2 concentrations and higher temperatures is unchanged. The results with maize leaf discs implied that there is very little oxidation of ribulose 1,5-bisphosphate under normal-air conditions; i.e., photorespiration is indeed suppressed, not merely hidden, by efficient refixation of CO2. PMID- 3101602 TI - Immunochemical studies on the contribution of NADPH cytochrome P-450 reductase to the cytochrome P-450-dependent metabolism of arachidonic acid. AB - We have studied the role of NADPH cytochrome P-450 reductase in the metabolism of arachidonic acid and in two other monooxygenase systems: aryl hydrocarbon hydroxylase and 7-ethoxyresorufin-o-deethylase. Human liver NADPH cytochrome P 450 reductase was purified to homogeneity as evidenced by its migration as a single band on SDS gel electrophoresis, having a molecular weight of 71,000 Da. Rabbits were immunized with the purified enzyme and the resulting antibodies were used to evaluate the involvement of the reductase in cytochrome P-450-dependent arachidonic acid metabolism by bovine corneal epithelial and rabbit renal cortical microsomes. A highly sensitive immunoblotting method was used to identify the presence of NADPH cytochrome P-450 reductase in both tissues. We used these antibodies to demonstrate for the first time the presence of cytochrome c reductase in the cornea. Anti-NADPH cytochrome P-450 reductase IgG, but not anti-heme oxygenase IgG, inhibited the NADPH-dependent arachidonic acid metabolism in both renal and corneal microsomes. The inhibition was dependent on the ratio of IgG to microsomal protein where 50% inhibition of arachidonic acid conversion by cortical microsomes was achieved with a ratio of 1:1. A higher concentration of IgG was needed to achieve the same degree of inhibition in the corneal microsomes. The antibody also inhibited rabbit renal cortical 7 ethoxyresorufin-o-deethylase activity, a cytochrome P-450-dependent enzyme. However, the anti-NADPH cytochrome P-450 reductase IgG was much less effective in inhibiting rabbit cortical aryl hydrocarbon hydroxylase. Thus, the degree of inhibition of monooxygenases by anti-NADPH cytochrome P-450 reductase IgG is variable. However, with respect to arachidonic acid, NADPH cytochrome P-450 reductase appears to be an integral component for the electron transfer to cytochrome P-450 in the oxidation of arachidonic acid. PMID- 3101603 TI - [Oncogenes, their implications in cell growth, differentiation and carcinogenesis]. AB - Cancer Research has changed substantially over the past several years since oncogenes were isolated from cancer cells. More than 40 oncogenes have been identified to date from tumor viruses and cancer cells. Many of the gene products seem related to signalling pathways that determine growth and differentiation of cells. This review attempts to summarize much of the currently available data and to gain future perspectives. PMID- 3101604 TI - [Enhancement of anti-tumor effects by arterial embolization combined with hyperthermia in the treatment of hepatic tumors]. AB - The effectiveness of arterial embolization using DSM (Degradable Starch Microspheres, Spherex, Sweden) combined with hyperthermia were investigated in the treatment of VX2 carcinoma in rabbits and also in human hepatic tumors. These microspheres temporarily obstructed the blood flow at the precapillary level. The blood flow in the tumor was inhibited to a greater extent and for a longer period than in normal muscle. The rise in temperature at the tumor site during heating was shown to be significantly higher than in muscle. The pH in the tumor clearly showed a stronger degree of inhibition than that achieved with hyperthermia alone. Histological examination demonstrated no marked damage to the muscle following DSM + hyperthermia. In the patients with hepatic tumor, hyperthermia was performed using an RF Thermotron 8 (8 MHz) externally, followed by injection of 15 ml of DSM combined with anti-cancer drugs via a catheter. The rise of temperature in DSM + chemo-hyperthermia during heating showed a higher value than that with hyperthermia alone and effective cases (PR) totalled 5 from among 8 cases treated. It was concluded that the heating efficiency may be improved by arterial chemo-embolization in the treatment of hepatic tumors. PMID- 3101605 TI - [Direct anti-tumor effect of recombinant human IFN-gamma evaluated in ovarian pseudomyxoma peritoneally transplanted into nude mice]. AB - Different doses of recombinant human interferon gamma (IFN-gamma) between 1 X 10(6) and 2 X 10(7) U/kg were administered to nude mice for 21 days continuously. As a result, an anti-tumor effect was noted in comparison with a control group, although there was no significant difference between groups at each dose level. Serum CEA value was found to decrease in the groups as follows: 1 X 10(6) U/kg, 71.5 +/- 10 ng/ml; 3 X 10(6) U/kg, 90.6 +/- 4 ng/ml; 8 X 10(6) U/kg, 56.5 +/- 0.7 ng/ml; 2 X 10(7) U/kg, 47.4 +/- 12 ng/ml. Generally, the level was found to decrease in groups with high-dose administration. There was no difference in histological effect between groups at each dose level, and also no strong anti tumor effect like that produced with other anti-cancer agents was noted with regard to histological change. It was revealed that recombinant human IFN-gamma was effective for suppression of tumor proliferation in human ovarian tumor, although its histological effect was less effective than that of anti-cancer agents such as Adriamycin and Cis-DDP. PMID- 3101607 TI - [Phase II study of recombinant human interferon gamma (S-6810) in renal cell carcinoma. Urological Cooperative Study Group of Recombinant Human Interferon Gamma (S-6810)]. AB - A phase II study of recombinant human interferon gamma (rHuIFN-gamma) administered intravenously and intramuscularly was carried out in 84 patients with advanced renal cell carcinoma with the cooperation of 18 institutions throughout Japan. The eligibility of the patients and evaluation of the responses were undertaken according to the general criteria proposed by Drs. Koyama and Saito. Out of 84 cases entered in this phase II study, 62 patients were evaluable for antitumor effects. In the case of continuous administration of 8-12 X 10(6) U/m2/day interferon for 4 weeks, 32 patients were evaluable. The response rate was 6.3%. In the case of intermittent therapy of 40 X 10(6) U/m2/day interferon for 8 weeks, six out of 30 patients (20%) were evaluable as responders. Among them, one patient showed a complete response, all patients tolerated this type of interferon well. Major adverse effects were fever (86.8%), anorexia (67.1%), fatigue (53.9%) and leukopenia (42.1%). No life-threatening toxicities were found. The results of this study showed that rHuIFN-gamma had antitumor activity against renal cell carcinoma. PMID- 3101606 TI - [Cooperative study of surgical adjuvant chemotherapy of colorectal cancer (first report): Investigation of background factors and adverse effects. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan]. AB - In order to evaluate the efficacy of surgical adjuvant chemotherapy in patients undergoing gross curative resection for colorectal cancer (excluding m and sm cancer), a randomized controlled study was conducted from January, 1982 to October, 1983. Four hundred and ninety-one institutions participated in this study. The schedules for drug administration differed according to each district. In the Hokkaido and Shikoku districts, the patients were divided into the following two groups, one was a combination of ACNU and Futraful (FT) and the other was FT only. In the Chubu and Kinki districts, three groups were studied, namely those receiving a combination of ACNU and FT, those receiving FT only and those given no adjuvant chemotherapy. In the Tohoku and Kanto districts, a combination of MMC and FT and administration of FT only were studied. In the Chugoku and Kyushu districts, the patients were divided into a combination of ADM and FT, and FT only group. Among the 3,926 registered cases, 3,421 cases were valid for the study. As to the background factors, there were no significant differences among the groups in each district. There were no significant differences in one-year survival rates and one-year disease-free rates. No serious adverse effects were observed in any of the groups. PMID- 3101608 TI - [Phase I study of a recombinant gamma interferon (S-6810)]. AB - A phase I study of a recombinant gamma interferon (S-6810) was conducted in a cooperative study involving 11 institutions. S-6810 was administered at doses of 2, 4, 8, 12, 32 and 64 X 10(6) U/m2 by one-hour infusion for 5 consecutive days. A total of 40 courses were administered to 31 patients. High fever exceeding 38 degrees C with chills occurred in about 80% of patients. The incidences of other toxicities were fatigue in 50%, gastrointestinal toxicities in 30-40%, and changes in hepatic enzymes and hematologic toxicities in 20-30%. Dose-limiting factors were judged to be hypotension, leukopenia and central nervous toxicity. Maximum tolerated dose was 64 X 10(6) U/m2 and an optimal dose for phase II study was considered to be 6 X 10(6) U/m2 by daily chronic schedule. Blood concentration was highest at the end of infusion, and then decreased rapidly with a biphasic curve. The peak concentrations were elevated by escalation of doses. A partial response was observed in a patient with mycosis fungoides. PMID- 3101610 TI - [A case of hypopharyngeal cancer responding to recombinant interferon-gamma (KW 2202)]. AB - A 66-year-old woman with hypopharyngeal cancer was treated with recombinant interferon-gamma (KW-2202). r-IFN-gamma was administered at a dose of 1-8 X 10(6) U/body every day for six weeks by i.v. drip infusion. After the start of the therapy both the primary tumor and metastatic lymph nodes showed remarkable regression and PR was obtained. Observed side effects, which included fever and hepatic function disorder, were slight and transient. Immunological studies were also carried out on the patients and the results were reported. Further investigation will be necessary in order to confirm the efficacy of the drug and to compile data on immunological parameters. PMID- 3101609 TI - [Synergistic action of lentinan (LNT) with endocrine therapy of breast cancer in rats and humans]. AB - With the aim of clarifying the nature of the synergistic action of LNT with endocrine therapy for mammary tumor, the effect of LNT post-treatment was investigated in rats with DMBA-induced mammary tumors and also in patients with recurrent breast cancer. LNT injection following surgical therapy (Ax + Ox) resulted in a much greater regression of tumor growth than that obtained by surgery alone, but not after medical therapy (Tamoxifen). Image analysis using an immunohistochemical technique revealed that LNT-surgical therapy resulted in marked atrophy of tumors and as well as intense infiltration of T cells, B cells and macrophages into the stroma around the tumor. Blood prolactin level was greatly reduced by LNT injection. A clinical randomized controlled study demonstrated the efficacy and safety of LNT post-treatment with surgical therapy in 33 patients with recurrent breast cancer. The mode of the synergistic action of LNT in combination with endocrine therapy on hormone-dependent tumors was discussed. PMID- 3101612 TI - Unilateral lichen planus: an unusual presentation. PMID- 3101611 TI - Congenital, segmental pigmented lesions. Segmental neurofibromatosis (SN). PMID- 3101613 TI - Complications of cutaneous laser surgery. A survey. AB - We surveyed a selected group of 139 dermatologists and plastic surgeons about their experience with the complications of cutaneous laser surgery. Reported complication rates varied from 0% to 35%, with means of 3.2% for dermatologists and 6.2% for plastic surgeons using the argon laser, and 4.2% for dermatologists and 2.8% for plastic surgeons using the carbon dioxide laser. Hypertrophic scarring was the complication noted most frequently; 69% of physicians using the argon laser and 64% of physicians using the carbon dioxide laser have seen at least one case of hypertrophic scarring. Complications noted less frequently include infection, pain, atrophic scarring, intraoperative or postoperative hemorrhage, and prolonged wound healing. Environmental accidents were few. No procedure-related deaths, ocular damage, or secondary cutaneous malignant neoplasms were reported. We conclude that cutaneous laser surgery has an acceptable risk profile but that complications are not uncommon. PMID- 3101614 TI - Nevus sebaceus associated with major ophthalmologic abnormalities. AB - Nevus sebaceus rarely occurs as part of a syndrome consisting of central nervous system and ophthalmologic abnormalities. We describe a case of nevus sebaceus associated with an epibulbar complex choristoma and colobomas of the optic disc and peripapillary choroid, and review the dermatologic, ophthalmologic, and neurologic literature on the nevus sebaceus syndrome. When associated with other developmental abnormalities, nevus sebaceus and epidermal nevus have erroneously been considered to be a single entity. In this article, we delineate and emphasize the ophthalmologic abnormalities associated with the nevus sebaceus syndrome. PMID- 3101615 TI - The medium chain triglyceride diet and intractable epilepsy. AB - Fifty children with drug resistant epilepsy were treated with the Medium Chain Triglyceride (MCT) Emulsion diet. Eight achieved complete control of seizures (four without anticonvulsant drugs), and with the addition of anticonvulsants four had seizures reduced in frequency by 90% and 10 by 50-90%. The best results were obtained with astatic myoclonic and absence seizures, but control of seizures was improved in four children with tonic-clonic and three with complex partial seizures. Food given at the same time as MCT helped to reduce side effects, and an extra dose of MCT before bedtime improved control of nocturnal seizures. PMID- 3101616 TI - Infantile colic and feeding. AB - In a double blind crossover study 10 children with infantile colic were fed breast milk and cow's milk formula, untreated and treated with lactase. Colic was present on 71% of breast milk and 89% of cow's milk days. Daily duration and severity of colic did not differ for milk preparations. PMID- 3101617 TI - Co-trimoxazole red cell aplasia in leukaemia. AB - A 4 year old boy with acute lymphoblastic leukaemia developed a pure red cell aplasia 13 months after entering remission and while on maintenance chemotherapy. Co-trimoxazole was also being administered for prophylaxis against Pneumocystis carinii infection. When co-trimoxazole was stopped the red cell aplasia resolved. PMID- 3101618 TI - Natural and concanavalin A-induced cytotoxic activity towards continuously growing B lymphocytes derived from patients with cutaneous T-cell lymphoma. AB - Continuously growing T- and B-cell lines were derived from peripheral blood, affected skin, and lymph nodes of patients with mycosis fungoides (MF) and Sezary syndrome (SS). Two lymphoblastoid cell lines (MF-13 and SS-2) were Epstein-Barr virus (EBV)-transformed B cells evaluated by surface immunoglobulin, lack of E rosette formation, positive EBV nuclear antibody test, and secretion of IgM antibody in a plaque-forming cell assay. Analysis of the natural-killer-cell activity using peripheral blood lymphocytes from patients with MF and healthy control persons towards MF-13 and SS-2 target cells suggested resistance to lysis even in tests supplemented with 1,000 IU/ml human gamma-interferon. However, the cell lines were not per se completely resistant to lysis because lymphocytes from control persons showed significant cytotoxicity in an 18-h assay supplemented with 2 micrograms/ml concanavalin A. PMID- 3101619 TI - Pharmacological studies on nonimmunologic contact urticaria in guinea pigs. AB - In the present study we examined the effects of chlorpheniramine and ranitidine, indomethacin, BW755C (an inhibitor of cyclo-oxygenase and lipo-oxygenase enzymes of arachidonic acid metabolism), dexamethasone, and capsaicin on nonimmunologic contact urticaria (NICU) induced in the guinea pig ear by benzoic, acid cinnamic acid, cinnamic aldehyde, methyl nicotinate, diethyl fumarate, or dimethyl sulfoxide. The intensity of edema in the urticarial reaction was quantified by measuring the ear thickness. Antihistamines inhibited reactions to intradermal histamine but not to agents causing NICU. Indomethacin and dexamethasone inhibited reactions to cinnamic acid and cinnamic aldehyde but not to other NICU agents. BW755C and capsaicin had no effect on reactions to any of the NICU agents. Mast cell degranulation during the reaction was not seen in histologic sections. Histamine and capsaicin-sensitive nerves did not seem to be essential for the development of NICU in the guinea pig ear. The details of the inhibitory effects of indomethacin and dexamethasone are not clear, but it seems probable that more than one mechanism is involved in NICU due to different agents. PMID- 3101620 TI - Toxicity of 3,4,5,3',4',5'-hexachlorobiphenyl to mink. PMID- 3101621 TI - Evidence for oligoclonal B cell expansion in the peripheral blood of patients with rheumatoid arthritis. AB - Peripheral blood lymphocytes from patients with rheumatoid arthritis and osteoarthritis were examined for evidence of oligoclonal B cell expansion using the computer assisted flow cytometric technique of kappa-lambda (kappa-lambda) analysis. Eleven of 29 patients with rheumatoid arthritis but only one of 16 with osteoarthritis gave abnormal results (p less than 0.025). Abnormal kappa-lambda determinations did not correlate with age, duration of disease, presence of rheumatoid factor, or other clinical and laboratory parameters. Therapy with oral or intramuscular gold compounds appeared to diminish the incidence of kappa lambda abnormality. These findings may indicate defective control of clonal B cell proliferation in rheumatoid arthritis. PMID- 3101622 TI - CD5 positive B cells in patients with rheumatoid arthritis: phorbol ester mediated enhancement of detection. AB - CD5 molecules present on human T cells are detectable but weakly expressed on some human B cells. We have increased the sensitivity of their detection by treating the B enriched cells with phorbol myristic acetate (PMA), a tumour promoting agent. The numbers of CD5+ B cells in the blood of patients with rheumatoid arthritis (RA) were higher than in control blood, and after PMA treatment this was statistically significant. CD5+ B cells were also increased in tonsils, lymph nodes, and spleens after PMA activation. There were no significant differences between the percentages of B cells carrying chi or lambda light chains in their expression of CD5 molecules in patients with RA. PMID- 3101623 TI - An investigation of the action of disease modifying antirheumatic drugs on the rheumatoid synovial membrane: reduction in T lymphocyte subpopulations and HLA-DP and DQ antigen expression after gold or penicillamine therapy. AB - Synovial needle biopsy specimens from the knee joints of seven patients with rheumatoid arthritis (RA) were examined immunohistochemically before and after six months' treatment with either gold or penicillamine (disease modifying drugs, DMDs). There were significant reductions in the numbers of infiltrating T lymphocytes and a disproportionate fall in the numbers of lymphocytes of the helper/inducer subset when compared with those of the suppressor/cytotoxic subset. This resulted in a fall in the ratio of helper/inducer to suppressor/cytotoxic cells. The immunohistological changes correlated with improvements in erythrocyte sedimentation rate (ESR), serum immunoglobulins, visual analogue pain assessment, grip strength, and Ritchie articular index. A second group of nine patients with RA, already well established on DMD therapy, did not show similar changes after the six month period. The HLA class II antigens DR, DQ, and DP were widely expressed on lymphocytes, macrophages, and synovial lining cells of a group of patients with RA who had never received disease modifying drug therapy. After treatment there was a significant reduction in the expression of HLA-DP and DQ antigens. PMID- 3101624 TI - Total parenteral nutrition prevents further nutritional deterioration in patients with cancer cachexia. AB - The effects of total parenteral nutrition (TPN) on some nutritional variables were prospectively investigated in 12 severely cachectic patients with advanced cancer. The following variables were determined before and at 5-day intervals during the 20-day administration of TPN: anthropometric indices (body weight, arm circumference, triceps skinfold, arm muscle circumference, arm muscle area, arm fat area, total body muscle mass); biochemical indices (total protein, albumin, cholinesterase, total iron binding capacity, thyroxin-binding prealbumin, retinol binding protein, urinary 3-methylhistidine and creatinine excretion, nitrogen balance); and peripheral lymphocyte count. TPN was delivered at 49.5 nonprotein kcal/kg-1/day-1 (80% as dextrose and 20% as fat) and amino acids 1.9 g/kg-1/day 1. A significant increase was obtained in body weight, triceps skinfold, arm fat area, and retinol binding protein. All remaining anthropometric and biochemical parameters did not show any significant positive or negative change, although nitrogen balance remained positive. No significant liver toxicity was apparent after the TPN period. It was concluded that although TPN is unable to completely reverse some nutrition-related variables in cachectic patients with cancer, most patients were kept within a normal range and some improved. Therefore, further deterioration of the nutritional state, which is characteristic of this phase of disease, was at least prevented. PMID- 3101625 TI - Hypothyroxinemia in cardiac arrest. AB - Thyroid function was evaluated in cardiac arrest (CA), a condition associated with marked activation of the pituitary-adrenal axis. Blood samples were obtained in 24 patients immediately after diagnosis of CA and again ten minutes later. Samples were also obtained from 22 patients admitted consecutively to the intensive care unit (ICU). Abnormalities of thyroid indexes among patients on the ICU who had not experienced CA were low triiodothyronine (T3) in 45%, low thyroxine (T4) in 32%, low free T4 (equilibrium dialysis) in 21%, and elevated reverse T3 levels in 36%. The alterations of thyroid values were both more common and marked in patients with CA, with abnormally low T3 in 84% of the patients, low T4 in 65%, low free T4 in 65%, and high reverse T3 in 80%. Thyroxine-binding globulin and prealbumin concentrations were below the normal range in 40% and 21% of patients with CA. A thyroid hormone-binding inhibitor was detected in 38% of patients with CA. Thyroglobulin level was slightly high in patients with CA but not significantly different from controls on the ICU. The abnormalities present at zero minutes were further exaggerated ten minutes after CA. We conclude that abnormalities on tests measuring thyroid function are extremely common during the cardiovascular emergency of CA. PMID- 3101626 TI - The acute arthritis-dermatitis syndrome. The changing importance of Neisseria gonorrhoeae and Neisseria meningitidis. AB - Sexually active young adults with an acute arthralgia or arthritis, with or without associated skin lesions, often have disseminated gonococcal infection (DGI). In recent years, an increasing proportion of patients seen with such complaints at the University of Washington Hospitals, Seattle, have had systemic meningococcal infection rather than DGI. Among 151 patients with acute arthritis studied prospectively from 1970 to 1972, blood or synovial fluid cultures yielded Neisseria gonorrhoeae in 30 patients and Neisseria meningitidis in two. Among 62 patients meeting the same criteria who were studied prospectively from 1980 to 1983, blood or synovial fluid cultures yielded gonococci in nine and meningococci in five. Separate analysis of blood culture results from two University of Washington Hospitals also revealed a decline in the number of cases of gonococcemia from 1970 through 1984 and a shift in the relative numbers of patients with bacteremia due to N gonorrhoeae and N meningitidis. The observed decline in gonococcemia coincides with a decline in the proportion of gonorrhea in Seattle caused by gonococcal strains that have been associated with DGI. PMID- 3101628 TI - [Laser angioplasty]. PMID- 3101627 TI - The head-eye-body turning behavior induced by electrical or cholinergic stimulation of the pulvinar-lateralis posterior nucleus complex is not dependent on the catecholaminergic system. AB - Two experimental designs were developed in cats in order to analyze the role of the catecholaminergic system in the turning response evoked by cholinergic or electrical stimulation of the pulvinar-lateralis posterior nucleus complex (P LP). Twenty one adult cats were employed. In one series of experiments, nine cats had a cannula implanted in one P-LP, and through it, apomorphine alone or mixed with carbachol were microinjected. The behavior was observed and the EEG was recorded. In the second experimental design, a cannula and bipolar electrodes were implanted unilaterally in the P-LP of nine cats, and a series of electrical stimulations were performed before and after 6-OHDA administration into the P-LP, and apomorphine was injected parenterally in order to induce turning behavior. Finally three cats received 16 micrograms of 6 OHDA into the P-LP, through a Hamilton syringe and no electrodes or cannula were implanted, to study the histological damage. No evidence of involvement of the catecholaminergic system was found in either of these two experimental series. These results contrast with what has been found in the nigrostriatal dopaminergic system, where an imbalance in dopamine concentration induces turning behavior. High doses (16 micrograms) of 6-OHDA induced minimal damage in the P-LP. PMID- 3101629 TI - [Dysfunction of bioprostheses. Respective value of echocardiography and of Doppler studies]. AB - The respective diagnostic values of M mode and 2D echocardiography and pulsed and continuous wave Doppler were assessed in bioprosthetic valve dysfunction. The results of the ultrasonic investigations were compared with the operative findings and anatomo pathological appearances in 56 cases of dysfunction. Only cases with surgical confirmation were included. Doppler examinations were carried out in 13 cases. Echocardiographic imaging alone cannot resolve all the diagnostic problems posed: specific signs are rare and were only observed in one out of 7 cases of periprosthetic leak, 7 out of 10 cases of valvular stenosis and 20 out of 36 cases (55 per cent) of valve tear. In cases of valve tear, 2D echocardiography was falsely normal in 15 per cent of cases and gave equivocal results in 30 per cent of cases because it was not possible to visualise the three cusps of the bioprostheses. Doppler echocardiography does not have the same limitations and gives an immediate and accurate assessment of valve function. It is particularly useful for the diagnosis of stenosis and valve tear in which the diagnostic specificity and sensitivity attain 100 per cent (exact diagnosis in all 11 cases of valve tear). At present, continuous wave Doppler seems to be the most reliable diagnostic tool for qualitative and quantitative assessment of primary degeneration of valvular prostheses. PMID- 3101630 TI - [Sequential internal mammary artery bypass for multiple coronary stenoses]. AB - Long-term studies (10 years) show a 50 per cent patency rate of saphenous vein autograft and 95 per cent patency rate of internal mammary artery coronary bypass grafts. In some situations (after saphenous vein stripping, varicose and fibrotic veins) it is not possible to use venous grafts and the internal mammary artery has to be used. However, the internal mammary artery is usually only used for revascularisation of the left anterior descending artery. Sequential internal mammary artery bypass is a technique which can be used for revascularizing the left anterior descending artery. Seven men aged 44 to 68 years (average 55 years) were operated between November 1983 and February 1985. These patients had clinically stable (4 cases) or instable (3 cases) angina. Two patients had previously undergone bilateral saphenous vein stripping and one patient a terminal anastomosis on the left anterior descending and a latero-lateral anastomosis on the diagonal artery. Three patients had an associated venous bypass graft and one patient also underwent aortic valve replacement. There were no cases of postoperative myocardial infarction. Five control angiographies were carried out during the first postoperative month. In 4 patients the internal mammary graft ant the latero-lateral and termino-lateral anastomoses were patent. In the other case, the latero-lateral anastomosis and the diagonal artery was occluded but the internal mammary graft and the termino-lateral anastomosis on the left anterior descending artery were patent. The average follow-up period is now 18 months: there have been no recurrences of chest pain or any ECG changes. These results show that internal mammary artery bypass grafting is a delicate procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101631 TI - [Follow-up angiography of 100 revascularizations of the anterior interventricular artery by the left internal mammary artery]. AB - One hundred and fifty patients who underwent revascularisation of the left anterior descending artery (LAD) by the left internal mammary artery (LIMA) between 1981 and 1983 were recalled for control coronary angiography one year after surgery. One hundred patients gave consent. The patency rate in these 100 patients was 90 per cent. The presumed causes of the 10 thromboses observed were: for LAD (5 cases), technical problems (3 cases), competitive flow (2 cases). Ten per cent of the patent LIMA grafts were abnormal: moderate stenosis of the anastomosis (5 cases), small LIMA (3 cases), stenosis of the middle segment of the LIMA (1 case). In addition, we observed 7 cases of competitive flows: 3 cases with a LAD which was not sufficiently stenotic, 4 cases with a large saphenous diagonal bypass graft. If a diagonal artery bypass is necessary, it is better to revascularize by either a latero-lateral anastomosis with the LIMA or by using the right IMA. Ninety per cent of the patent grafts were quite satisfactory ar 1 year: regular, supple, and perfectly congruent with the bypassed artery which was injected massively. As a number of North American teams have shown, this good patency rate seems to be maintained at long term, which is not the case with saphenous vein bypass grafts. PMID- 3101632 TI - [Evaluation of aortocoronary bypass using exercise myocardial thallium 201 scintigraphy]. AB - The surveillance of aortocoronary bypass grafts is a difficult problem. Clinical examination and exercise testing are unable to give a complete evaluation of the operative results and cardiac catheterisation with radiological opacification of the grafts are not without risk and cannot be repeated periodically. Therefore, radioisotopic methods have been proposed as a means of assessing aortocoronary bypass grafts. The aim of this study was to evaluate postoperative myocardial perfusion by Thallium 201 scintigraphy. The authors compared pre and postoperative scintigraphies in 37 patients undergoing aortocoronary bypass surgery (36 men and 1 woman, average age: 53.9 years). Preoperative coronary angiography showed 9 cases of single vessel disease, 11 cases of double vessel diseases and 17 cases of triple vessel disease. Seventy one bypass grafts were performed (average 1.92 grafts/patient): 37 on the LAD, 15 on the circumflex, 10 on the diagonal and 9 on the right coronary. All patients were submitted to the same protocol before surgery and during the third postoperative month; Clinical examination, ECG, exercise stress testing and Thallium 201 myocardial scintigraphy. The results confirm the improvement in myocardial perfusion after coronary bypass surgery. The percentage of pathological scintigraphic segments fell from 42 per cent before surgery to 27 per cent after surgery (p less than 0.01). The total Thallium perfusion index improved significantly after surgery from 9.3 +/- 2 to 7.7 +/- 1.9 (p less than 0.01). Thallium 201 scintigraphy was superior to clinical examination and exercise testing in the assessment of graft patency, identifying 2 postoperative infarctions inapparent on clinical examination, excluding postoperative non-anginal chest pain and evaluating myocardial perfusion in patients who had sub maximal postoperative exercise stress tests. The relatively non traumatic character of Thallium 201 scintigraphy makes it the best non-invasive method of assessing aortocoronary bypass graft patency. PMID- 3101633 TI - [Perioperative myocardial infarct following aortocoronary bypass. Clinical aspects, causes, consequences]. AB - Perioperative infarction is a significant factor of morbidity of coronary bypass surgery. The aim of this study was to review peri-operative infarction and its complications over a 10 year period (1974 to 1984) and to determine its consequences on left ventricular function and life expectancy. The material included 514 patients who underwent coronary bypass surgery. Perioperative infarction was defined as the association of a postoperative Q wave and increase in creatinine phosphokinase after the 24th postoperative hour: this diagnosis was made in 31 cases (Group A), 6 per cent of the series; 483 patients (Group B) had no signs of infarction. The necrosis involved the revascularised zone in 26 cases and other zones in 5 cases. The acute phase of infarction was associated with major complications in 9 patients of Group A. In 22 patients (70 per cent of cases) the initial evolution was uncomplicated. There was no significant difference in the number of patients with unstable angina between Groups A and B (52 per cent vs 67 per cent), with single vessel disease (25 per cent vs 28 per cent), double vessel disease (45 per cent vs 34 per cent) or with triple vessel disease (30 per cent vs 38 per cent). The average number of bypasses was higher in Group A (2.06 per cent vs 1.4 per cent, p less than 0.05), as was the duration of cardiopulmonary bypass (117 min vs 91 min, p less than 0.05) and of aortic clamping (45 min vs 31 min, p. less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101634 TI - [Simplified technic for the resection of aneurysms of the ascending aorta with aortic insufficiency]. AB - The authors propose a simplified technique for the resection of dystrophic aneurysms of the ascending aorta with aortic regurgitation. The technique is based on a special method of shaping the Dacron tube, so that the proximal line of suture extends to the bottom of the sinuses of Valsalva, in front of and behind the coronary ostia. The results in 27 operated patients are reported. The global hospital mortality was nil. Seventy four per cent of patients had no complications at all 22 per cent had minor and rapidly regressive complications. The long-term results were assessed in 20 patients. There were no secondary deaths or reoperations. Angiographic and/or echocardiographic control performed in 12 cases showed no valvular dysfunction or recurrence of the aneurysmal process. The advantages of this technique are its simplicity, its good short and long-term results and the possibility of using a bioprosthesis for aortic valve replacement. PMID- 3101635 TI - [Short and intermediate-term hemodynamic study at rest and during exercise of cardiac insufficiency treated by captopril]. AB - Administration of 25 mg of captopril to 10 patients with heart failure (NYHA II, III) produces at rest after 60 min bradycardia (-7 per cent, p less than 0.01), hypotension (-8 per cent) and improvement of the preload (-30 per cent, p less than 0.01). This effect is still apparent after two months of treatment where PAP is decreased by 20 per cent (p less than 0.05). A prolonged effect of captopril is present in these 10 patients. The capacity to perform a muscular exercise on an ergometric bicycle is prolonged by 10 per cent (p less than 0.01) on the first day and by 18 per cent (p less than 0.01) after two months of treatment. This improvement seems to be related to improvement of the hemodynamic parameters, especially of preload indices. In 5 patients, lactacidemia, the arterio-venous difference and the extraction coefficient of O2 were studied at rest and during exercise. No significant difference are noted after the treatment with the inhibitors of conversion enzymes. PMID- 3101637 TI - [Intra-sinus echo: demonstration using direct intracavitary recording of the sinus potential]. AB - The authors searched for intra-sinusal echos during electrophysiological investigation of 53 patients (41 men, 12 women, average age: 61 +/- 12 years). Cycles of sinus echos were recorded in 8 patients (15 per cent). The period during which sinus echos could be recorded was 125 ms (average 40.6 +/- 34 ms). Indirect assessment of sinus node function in patients with sinus echos was normal (corrected sinus node recovery time, estimated atrio-sino atrial conduction times using Narula's technique). A valid and reproducible direct recording of the sinus node potential was only possible in one patient. In this case the echo cycles were provoked by stimulation periods of between 440 and 320 ms (echo zone of 120 ms). All the echos obtained were preceded by a sinus node potential with a different duration and morphology to that observed during basal sinus cycles (respective sino-atrial conduction times 105 and 115 ms). In this patient we were also able to induce sinus echos after a single extrastimulus during the spontaneous rhythm. the echo zone was 130 ms and with a shorter coupling interval (310 ms) two successive sinus echos were recorded. The demonstration of intrasinusal echos by direct recording of the sinus node potential supports the experimental data of Allessie and Bonke on isolated right atrial tissues of the rabbit. Improvements in the technique of endocavitary direct recording of the sinus node potential in man should complete this data by showing the possibility of sinoatrial tachycardias due to reentry. PMID- 3101636 TI - [The effects of trimetazidine on ergometric parameters in exercise-induced angina. Controlled multicenter double blind versus placebo study]. AB - The antianginal effect of trimetazidine was assessed by a controlled multicentre double-blind versus placebo trial. The study included 32 males, average age 59.5 years, with stable angina of effort. The stability of angina was determined by two exercise stress tests performed at the beginning and at the end of a 15 day pre-selection period under placebo. The patients included in the trial were given 3 tablets a day of either trimetazidine (20 mg per tablet) or of placebo for one month. At the end of the treatment period the patients underwent a third exercise stress test. Comparing the results of exercise testing before and after treatment by a Mann and Whitney test, a statistically significant improvement with trimetazidine was demonstrated with respect to placebo for three parameters: total work increased from 4200 +/- 372 to 5620 +/- 387 Kpm in the trimetazidine group compared to 4191 +/- 399 to 4564 +/- 431 Kpm for placebo (p = 0.012); the duration of exercise increased from 10.2 +/- 0.5 to 12.1 +/- 0.5 minutes with trimetazidine compared to 10.2 +/- 0.5 to 10.7 +/- 0.5 with placebo (p = 0.016); the period to 1 mm ST depression increased from 8.3 +/- 0.6 to 9.8 +/- 0.5 minutes with trimetazidine compared to 8.4 +/- 0.5 to 9.0 +/- 0.7 minutes with placebo (p = 0.034). These results show that signs of ischaemia are delayed by trimetazidine. There were no significant changes in peripheral haemodynamics at rest or on effort. The antianginal action of trimetazidine seems therefore to be unrelated to a chronotropic or vasomotor effect and could be related to a mechanism of cellular regulation. PMID- 3101638 TI - [Ultra-sensitive TSH levels: an aid in the screening for amiodarone-induced thyroid dysfunction]. AB - Amiodarone modifies thyroid hormone secretion and hypothyroidism occurs in some cases. The latter diagnosis is often difficult and is of particular importance in these patients as it may have serious consequences for the heart. Early diagnosis is therefore essential but difficult because of the induced hyperthyroxinemia with maintenance of euthyroidism and a hypotriiodothyronemia. The diagnostic performance of an ultrasensitive method of measuring TSH (TSH-U), capable of distinguishing hyper and euthyroidism were compared with standard thyroid function tests and TSH stimulation with TRH in 50 patients treated with amiodarone. Only 6 of the 14 patients with hyperthyroxinaemia had TSH-U values in the hyperthyroid range: only one of these patients had an increased triiodothyronine. In 2 cases the THS-U was low but the T4L was normal. In 4 patients, increased TSH-U allowed diagnosis of latent or patent hypothyroidism. There was a close correlation between results of the TRH stimulation test and those of the TSH-U in all cases. This test may therefore be used as an initial screening test for thyroid dysfunction in patients on amiodarone and is simple, reliable and relatively cheap to perform. It makes it unnecessary to measure all thyroid hormonal parameters and the TRH test simultaneously. PMID- 3101639 TI - [Methods of detecting and monitoring ventricular excitability in coronary patients. Electric provocation of ventricular tachycardia and late ventricular potentials]. PMID- 3101640 TI - [Detection of cardiac graft rejection using proton nuclear magnetic resonance]. AB - Rejection of cardiac transplants can be detected by NMR imaging if it is associated with a change in myocardial T1 and/or T2 proton relaxation time. T1 and T2 were studied in 14 Lewis rats that underwent heterotopic cardiac transplantation. T1 and T2 were measured in vitro immediately after sacrifice 3, 4, 7 or 11 days after the graft using a Minispec BRUKER PC20. The myocardial water content was measured by dehydration in a vacuum for 24 hours. Histological analysis of sections classified the rejection process in 4 stages according to the degree of lymphocyte infiltration and percentage of myolysis. There was a significant difference between the ortho and heterotopic hearts: (Formula: see text). In particular, there was highly significant relationship between T2 and the stage of rejection (r = 0.90, p less than 0.005), and between T2 and % myolysis (r = 0.84, p less than 0.005). In addition, there was a close relationship between the T2 of the ortho and heterotopic hearts and their water content (r = 0.95, p less than 0.001). If these results are confirmed in man, is should be possible to detect rejection by NMR imaging using sequences of activation concentrating on changes of T2. PMID- 3101641 TI - [Sinoatrial and atrioventricular conduction disorders in Lyme disease. Apropos of 2 case reports]. AB - Lyme's disease due to Borrelia Burgdorferii is a rare cause of acute atrioventricular block (AVB) which is the commonest cardiac complication. Cutaneous, neurological and articular involvement complete the clinical picture of this condition. These two cases, confirmed by serology, support previously reported data describing the favourable prognosis of these conduction defects (suprahisian and/or hisian in our 2 cases) which regress completely, irrespective of their degree of severity. The authors also describe AVB occurring without extracardiac manifestations of this condition and a documented case of sinoatrial block, indicating a new zone of infestation. PMID- 3101642 TI - [Thrombus of the left auricle: a rarely noticed cause of systemic embolism. Apropos of an echocardiographic case report]. AB - The authors report the case of a 70 year old woman who had 3 episodes of acute ischaemia of the lower limbs in the space of 2 months. She was admitted to the Cardiology Unit after the second embolism: successive ECG recordings showed signs of the sick sinus syndrome justifying permanent pacing and anti-arrhythmic and anticoagulant therapy. The standard 2D echocardiographic views showed no signs of intracardiac disease, but a modified high short axis view demonstrated an oblong thrombus in the left auricle. Unfortunately, therapeutic non-compliance led to a third episode of embolism 2 weeks later; a repeat 2D echocardiogram showed the left auricle to be completely free of thrombosis. The authors review the medical literature of this condition. Echocardiography only began to play a useful diagnostic role from 1984 when technical improvements and the use of new and more appropriate views of the left auricle were introduced. PMID- 3101643 TI - [Polymorphic atrial tachycardia and Wolff-Parkinson-White syndrome in a newborn infant]. AB - The authors report a case of polymorphic supraventricular tachycardia in a premature neonate born at 33 weeks by caesarean section because of foeto placental insufficiency and hydramnios due to foetal tachycardia diagnosed in utero. This arrhythmia was of interest because of the association of chaotic atrial tachycardia and the Wolff-Parkinson-White syndrome (WPW), which has rarely been described in the neonate. The mechanism of atrial tachycardia in the WPW syndrome is variable. In our case, there was retrograde atrial activation by the accessory pathway with atrial desynchronisation aided by left atrial dilatation. Digoxin, an effective anti arrhythmic agent in neonatal tachycardia, should not be used in cases of atrial tachycardia associated with ventricular preexcitation because of the risk of dangerous ventricular tachycardia. PMID- 3101644 TI - [Abnormal origin of the left coronary artery. Pre- and postoperative hemodynamic and metabolic studies]. AB - The authors report the case of an asymptomatic 45 year old man in whom an abnormal origin of the left coronary artery was discovered fortuitously. Coronary angiography was carried out for electrocardiographic signs of anterior myocardial infarction and showed the left coronary artery arising from the pulmonary artery: there was apical dyskinesia with alteration of global left ventricular function. The ostium of the left coronary artery was closed and a saphenous vein aorto-left anterior descending artery bypass was performed. There were no complications. Left ventricular function has not improved 8 months after surgery. The haemodynamic and coronary signs of myocardial ischaemia demonstrated preoperatively regressed after surgery: the coronary "steal" caused by the malformation which led to poor perfusion of the territory of the left coronary artery has therefore been corrected by surgery. This procedure should be carried out as early as possible in order to limit extension of the myocardial lesions. PMID- 3101645 TI - [Role of pelvic ultrasonography in the diagnosis, therapeutic indications and surveillance of central precocious puberty]. AB - The use of pelvic ultrasonography was evaluated as a diagnostic and follow-up tool in girls with precocious puberty. Before treatment 23 of 33 patients with central precocious puberty presented an increased size of the uterus. In 10 cases with prepubertal size of the uterus, the precocious puberty was only beginning or of mild severity. During treatment with a LHRH analogue, changes in uterine size were slow in spite of a satisfactory and rapid control of estrogen secretion. At onset of treatment, transient ovarian cysts were seen in 2 patients. In our experience, pelvic ultrasonography did not provide significant information on the control of the disease by LHRH analogue therapy. Of 16 girls with presumed premature thelarche, 3 presented signs of estrogenic stimulation of the uterus. It remains a useful technique to rule out the presence of ovarian cysts or tumors at time of diagnosis. PMID- 3101646 TI - [Intestinal parasitic colonization and protein-caloric malnutrition]. AB - Intestinal parasitic infection was determined by fecal examination for parasites with several complementary methods in 380 young Gabonese infants aged 6 to 24 months (190 with normal weights and 190 with malnutrition, matched for age). Trichuris trichiura, Ascaris lombricoides, Giardia intestinalis, Entamoeba histolytica and Strongyloides stercoralis were the most prevalent parasites, without any difference between well-fed infants and patients with malnutrition. The higher prevalence of Strongyloides stercoralis in protein energy malnutrition might be related to a methodologic problem. However, more than 20% of diarrheas in infants with severe malnutrition were dramatically improved by specific treatment of S. stercoralis or Giardia with thiabendazole or metronidazole. PMID- 3101647 TI - Schizoaffective psychosis. I. Comparative long-term outcome. AB - Patients from the Chestnut Lodge (Rockville, Md) follow-up study with schizoaffective (SA) psychosis (n = 68) were compared with patients with DSM-III schizophrenia (S, n = 163), bipolar disorder (n = 19), and unipolar disorder (n = 44) on multiple premorbid, morbid, and outcome dimensions. This study required that patients with SA disorder satisfy DSM-III criteria for both S and affective disorder (minus mutual exclusionary criteria). The SA cohort demographic and premorbid profile paralleled that of the cohort with unipolar disorder. At follow up, however, the profile of SA psychosis paralleled that of S, with no significant differences between these patients on virtually all outcome measures. Results suggest that among samples of long-term inpatient, SA psychosis as defined herein is closer to S than affective disorder. PMID- 3101648 TI - The lupus anticoagulant. PMID- 3101649 TI - The sensitivity of different coagulation reagents to the presence of lupus anticoagulants. AB - The sensitivity and responsiveness of seven activated partial thromboplastin time reagents to the presence of lupus anticoagulants (LAs) was evaluated with a panel of 50 well-characterized LA plasmas. The results document that some reagents are clearly less responsive and sensitive to LAs; however, there is considerable variability between individual LA samples in these features. In addition, with 16% of these samples, immediate mixing studies showed correction of the activated partial thromboplastin time to the normal range with a 1:1 mixture of normal and LA plasma and 8% to 10% showed either a normal platelet neutralization procedure or a normal tissue thromboplastin inhibition procedure. Together, these findings provide further evidence of the laboratory heterogeneity of these inhibitors. The effect of this variability on the diagnosis of these inhibitors is discussed. PMID- 3101650 TI - Adult Fanconi syndrome in kappa light chain myeloma. AB - Distinctive morphological features in both the marrow infiltrate and the kidney were seen in a 52-year-old woman with kappa light chain-producing plasma cell myeloma, diagnosed on the basis of multiple osteolytic lesions, the presence of atypical plasma cells in the bone marrow, and monoclonal immunoglobulin production as demonstrated by immunoperoxidase staining on marrow sections. Large focal collections of histiocytes in the bone marrow and the renal proximal tubular epithelium had abundant glassy cytoplasm. Characteristic crystalline inclusions were seen ultrastructurally in both types of cells. It is believed that these crystalline deposits are lysosomal inclusions composed of altered kappa light chains taken up by these cells. The renal changes were entirely different from those of myeloma kidneys and were associated with proximal tubular dysfunction of adult Fanconi syndrome without distal tubule abnormality. PMID- 3101651 TI - Histopathological and morphometrical analysis applied to skin changes in NMRI mice induced by dithranol (anthranil) and its acyl analogs. AB - Histology and morphometric changes in skin lesions of NMRI mice caused by dithranol and its acyl analogs, with and without pretreatment with dimethylbenzanthracene (DMBA) are described. The course of neoplastic progression seems to have three distinct phases (normal skin, hyperplasia, papilloma), each characterized by typical architectural and cellular changes. The parameters reflecting the nuclear size increased in the above order and the differences between the groups were highly significant. Nuclear shape changes did not take place, as shown by the almost constant form factor. The study demonstrates the value of the morphometric methodology in characterizing quantitative nuclear changes in mouse skin models. PMID- 3101652 TI - Proteins specified by African swine fever virus: V. Identification of immediate early, early and late proteins. AB - Autoradiographic analysis of polypeptides separated by polyacrylamide gel electrophoresis revealed that, after infection with ASFV, MS cells synthesized at least 44 new polypeptides, that could be classified as immediate early, early or late proteins. A new viral polypeptide (IP 78) was detected by treatment of cells with cycloheximide for 14 hours. PMID- 3101654 TI - Effects of MY-5116 on experimental asthma in rats and guinea pigs. PMID- 3101653 TI - Detection of DNA viruses by radioactive and non radioactive DNA probes: application to African swine fever virus. AB - A molecular hybridization technique using radioactive and non radioactive DNA probes, has been used to detect ASFV DNA immobilized on nitrocellulose paper. It is based on the use of plasmid pRPEL-2 as a hybridization probe. This plasmid contain the H-ClaI DNA fragment (size 5.6 Kbp) from the Spain-70 strain of ASFV. The sensitivity of detection using radioactive 32P-probes (specific activity about 2 X 10(8) cpm per microgram) was about 20 pg of viral DNA. The 32P-pRPEL-2 DNA probe can detect about 100 infected MS cells and failed to hybridize to DNA from HSV-2, MS cells or salmon sperm. The sensitivity with non radioactive probes was about 4 ng of viral DNA for a sulfonated DNA probe and 400 pg for a biotinylated DNA probe. The efficiency of DNA fixation to the filter, the effect of EDTA and of ultrasonic treatment of the sample were also investigated. PMID- 3101656 TI - Design of a shadow shield counter for the measurement of total body potassium. PMID- 3101655 TI - Enhanced production of gamma-interferon by therapy with parenteral OK-432 and alpha-interferon in patients with head and neck cancer. AB - Although the drug OK-432 can induce the release of gamma-interferon (IFN-gamma), the serum concentrations of IFN-gamma produced are very low. We studied the effects of combining OK-432 with alpha-interferon (IFN-alpha) on the endogenous production of IFN and the postoperative courses of patients with oral cavity cancers. Forty patients operated on for head and neck cancers were studied. Each patient was given an injection of OK-432 1 week after surgery. Between 10 and 14 days later, a combination of OK-432 and IFN-alpha was given to assess the effects of the concomitant use of IFN-alpha on IFN production. In 18 of the 30 patients given a large dose of IFN-alpha (3 or 5 X 10(6) IU/mg protein), IFN production induced by OK-432 was enhanced. A small dose of IFN-alpha (7 X 10(3) IU) did not enhance the action of OK-432. OK-432 also induced the release of both endogenous IFN-gamma and IFN-alpha, and the production of both types of IFN was enhanced by the concomitant administration of parenteral IFN-alpha. Next, 50 patients operated on for oral cavity cancers were given OK-432 or a combination of OK-432 and IFN-alpha for 4 months, and their postoperative courses were followed for 2-5 years. The clinical courses were better in the combined therapy group than in the group given OK-432 alone. PMID- 3101658 TI - Computed tomography prior to surgery for ovarian carcinoma. AB - The value of investigation of patients with ovarian carcinoma by preoperative computed tomography scan was evaluated in all the patients operated on during the last 2 years; 22 patients were included in this study and evaluated. In 11 patients the scan was performed prior to the primary surgery and in the other 11 patients before second look following chemotherapy. CT scan was found to be highly sensitive in detecting ascites, pelvic wall extension and spread or involvement of the uterus. Peritoneal and omental spread was detected in only half of the patients before primary surgery. Prior to second look operation CT scan was effective in excluding liver metastasis, ascites, paraaortic lymph node enlargement, pelvic wall extension and pelvic residual tumour. Generally, CT scan failed to detect peritoneal and omental spread. It is an important tool for preoperative evaluation of the extension of the disease and planning of surgery, but still, the final staging deserves explorative laparotomy. PMID- 3101657 TI - Distribution and clearance of aflatoxins B1 and M1 in turkeys fed diets containing 50 or 150 ppb aflatoxin from naturally contaminated corn. AB - Turkeys were fed a diet containing 50 or 150 ppb aflatoxin for 11 or 13 weeks or fed these diets for 11 weeks and then the control diet for 1 or 2 weeks. Aflatoxins B1 and M1 were found in liver, kidney, gizzard, and feces of poults fed the diets for 11 or 13 weeks. However, in turkeys fed the control diet for 1 or 2 weeks after the 11-week feeding trial, no residues of aflatoxin were found in the feces or tissues, except for some aflatoxin B1 remaining in detectable amounts in the gizzard. No mortality was attributable to aflatoxin, and there were no notable differences among groups in weight gains, feed conversion, or histopathologic changes in selected tissues. The response to a second inoculation with sheep erythrocytes was significantly lower in poults given dietary aflatoxin than in controls. This reduced antibody response was not observed when a Pasteurella multocida vaccine was administered. PMID- 3101660 TI - Implications of emerging isoniazid resistance in Mycobacterium tuberculosis in Korea. AB - In 1981, the Korean National Institute of Health (KNIH) reported that 17% of all tuberculosis patients had primary resistance to isoniazid while an additional 17% acquired isoniazid resistance during chemotherapy. This 34% isoniazid resistance rate in the Republic of Korea, where an estimated 6-8% of the total population have active tuberculosis, poses significant concerns regarding management of U.S. military health care beneficiaries who develop tuberculosis or have tuberculosis skin test conversion while residing in or after departure from Korea. To address this issue, the prevalence of Korean acquired isoniazid resistance was estimated in U.S. beneficiaries by performing antibiotic sensitivities on all positive cultures from October 1981 through December 1982. Of 42 patient isolates, six were isoniazid resistant (14.3%). When the data was analyzed further, it was determined that as many as 9.5% of those U.S. beneficiaries infected had primary isoniazid resistance. This is higher than the most recent U.S. population-based drug resistance study, in which 6.9% of tuberculosis patients had primary drug resistance. This data comparison points toward the need for judicious management of Korean acquired infections and skin test conversions. Emphasis is on criteria necessary to warrant use of chemotherapeutic agents other than isoniazid to prevent further introduction of resistant organisms into locales where isoniazid resistance is not as prevalent as reported in Korea. PMID- 3101659 TI - A comparison of circulating immune complexes, pregnancy associated beta 1 macroglobulin and galactosyltransferase as tumour markers for ovarian cancer. AB - Serial blood samples have been obtained from 12 patients with ovarian cancer who were treated by surgery and, generally, chemotherapy or radiotherapy. Some achieved clinical remission, but the majority relapsed after variable time interval. Three potential tumour markers (Circulating Immune Complexes, Pregnancy Associated beta 1-Macroglobulin and Galactosyltransferase) have been studied longitudinally in serum for clinical correlation, predictive value, and biochemical 'lead time' to clinically detectable progression. None of the 3 offered any signal advantage over the others, and each showed an inconsistent relationship to observed disease status, with high levels indicating a poor outlook and the converse not true. Thus, since the 'lead time' is short, and reliability low, none of the compounds can be strongly commended as individual markers for ovarian cancer. PMID- 3101661 TI - Effects of neonatal forebrain noradrenaline depletion on recovery from brain damage: performance on a spatial navigation task as a function of age of surgery and postsurgical housing. AB - The experiments examined the contributions of forebrain noradrenaline and environmental enrichment to recovery of place navigation ability in rats after hemidecortication in infancy or adulthood. Noradrenaline depletion did not affect recovery from neonatal hemidecortication, although the early hemidecortications did allow sparing of function relative to adult operates. Noradrenaline depletion also failed to attenuate the positive effects of enriched housing on otherwise normal rats. Noradrenaline depletion did retard recovery of adult hemidecorticate rats housed in standard laboratory cages, but it did not retard recovery of adult hemidecorticate rats housed in enriched environments. The results suggest that noradrenaline is importantly involved in enhancing recovery from brain damage when other sources of compensation (e.g., neonatal injury, enriched environment) are absent. PMID- 3101662 TI - Antibody-mediated enhancement of infection by dengue virus of the P815 murine mastocytoma cell line. AB - Dengue type 2 virus (DEN 2) could replicate only to a limited extent in a murine mastocytoma cell line, P815. The viral multiplication was enhanced 10- to 100 fold by mouse anti-DEN 2 antiserum or anti-DEN 2 type-specific monoclonal antibody diluted beyond their neutralizing titers. Cells incubated with virus antibody mixtures changed morphologically, developing a mature mast cell-like appearance, 4-5 days after infection. The indirect fluorescent antibody technique showed that the enhancement of infection was caused by an increase in the number of DEN 2-infected cells. This is the first report that cells of mast cell lineage support dengue virus multiplication, and that virus production is enhanced in the presence of anti-dengue antibodies. PMID- 3101663 TI - Selective action of mycobacillin on the uptake of releasable cell materials by Aspergillus niger. AB - The uptake of normally releasable (i.e. releasable in the absence of the antibiotic) cell constituents (namely lysine, proline, ATP, Pi, Na+, K+ and Ca2+) by sensitive cells of Aspergillus niger that occurs in the absence of mycobacillin is gradually enhanced with increase in concentration of the antibiotic until the uptake attains the maximum. With still higher concentrations the uptake decreases until it becomes the same as in the control without mycobacillin. Uptake follows saturation kinetics both in the absence and in the presence of the antibiotic. Mycobacillin significantly increases Vmax. for uptake with any effect on Km, Mycobacillin has no action on the uptake of non-releasable materials. PMID- 3101664 TI - Purification and characterization of sheep platelet cyclo-oxygenase. Acetylation by aspirin prevents haemin binding to the enzyme. AB - Arachidonate cyclo-oxygenase (prostaglandin synthetase; prostaglandin endoperoxide synthetase; EC 1.14.99.1) was purified from sheep platelets. The purification procedure involved hydrophobic column chromatography using either Ibuprofen-Sepharose, phenyl-Sepharose or arachidic acid-Sepharose as the first step followed by metal-chelate Sepharose and haemin-Sepharose affinity chromatography. The purified enzyme (Mr approximately 65,000) was homogeneous as observed by SDS/polyacrylamide-gel electrophoresis and silver staining. The enzyme was a glycoprotein with mannose as the neutral sugar. Haemin or haemoglobin was essential for activity. The purified enzyme could bind haemin exhibiting a characteristic absorption maximum at 410 nm. The enzyme after metal chelate column chromatography could undergo acetylation by [acetyl-3H]aspirin. The labelled acetylated enzyme could not bind to haemin-Sepharose, presumably due to acetylation of a serine residue involved in the binding to haemin. The acetylated enzyme also failed to show its characteristic absorption maximum at 410 nm when allowed to bind haemin. PMID- 3101665 TI - Post-translational modification of the protein-synthesis initiation factor eIF-4D by spermidine in rat hepatoma cells. AB - The rates of synthesis and turnover of the rare amino acid hypusine [N6-(4-amino 2-hydroxybutyl)-2,6-diaminohexanoic acid] in protein were studied in relationship to polyamine metabolism and growth rates in rat hepatoma tissue-culture (HTC) cells. Hypusine is selectively formed in the eukaryotic translation initiation factor eIF-4D, by a post-translational mechanism involving spermidine [Cooper, Park, Folk, Safer & Braverman (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 1854 1857]. The half-life of the hypusine-containing protein was longer than 24 h. In cells whose intracellular spermidine pools had been initially depleted, by using DL-alpha-difluoromethylornithine (DFMO), maximum synthesis rates of hypusine in protein were 5-10 times higher, on restoration of endogenous spermidine contents by exogenous addition, than those observed in untreated exponential-phase cultures. In cells pretreated with DFMO, the rate of hypusine synthesis was constant for up to 1 h after the addition of 5 microM-spermidine, whereas endogenous spermidine contents varied from less than 1 to more than 10 nmol/mg of protein. However, the overall amount of hypusine formed, during the first 1 h after the addition of various concentrations of spermidine (0.05-10 microM) to the culture medium, was markedly dependent on the final endogenous spermidine content achieved at the end of the 1 h measurement interval. Early in exponential phase growth, protein-bound hypusine was synthesized at a rate of 1-2 pmol/h per mg of protein. This rate decreased to less than 0.5 pmol/h per mg of protein when cell growth rates decreased as cultures reached high cell densities. Analysis of the polyamine substrate specificity for hypusine formation showed that N1 acetylspermidine did not compete with spermidine in the reaction, nor did N1 (buta-2,3-dienyl)-N2-methylbutane-1,4-diamine, and irreversible inhibitor of polyamine oxidase, block the reaction. On the basis of comparative radiolabelling experiments, spermine was either a poor substrate, or not a substrate, for hypusine formation. These results confirm that spermidine is the likely precursor of the aminohydroxybutyl moiety of hypusine, and show that overall hypusine formation, but not necessarily the synthesis rate, is dependent on the endogenous spermidine concentration, especially under conditions where spermidine concentrations are initially low, as is the case after DFMO treatment, and then increase. PMID- 3101667 TI - Increased hyaluronate synthesis is required for fibroblast detachment and mitosis. AB - Human-embryo fibroblasts were synchronized by means of colchicine and cytochalasin, and the production of hyaluronate was determined by [3H]glucosamine incorporation and ion-exchange chromatography. Cells arrested by colchicine synthesized small amounts of hyaluronate, whereas cells blocked by cytochalasin were stimulated in hyaluronate production. When the colchicine block was released, there was an increased synthesis of hyaluronate, which appeared first in the cellular fraction and was then shed into the culture medium. After release of the cytochalasin block, the hyaluronate production declined to that found with unsynchronized cells. A comparable increase of hyaluronate synthase activity was observed during mitosis. When hyaluronate synthesis was blocked by periodate oxidized UDP-glucuronic acid, the cells were arrested in mitosis before rounding of cells. These results suggest that hyaluronate synthesis is required for detachment and rounding of cells during mitosis. PMID- 3101666 TI - Cationic activation of galactosyltransferase from rat mammary Golgi membranes by polyamines and by basic peptides and proteins. AB - Galactosyltransferase (EC 2.4.1.22) requires bivalent metal ions for its activity. However, preparations of this enzyme solubilized from Golgi membranes of lactating rat mammary gland were shown to be activated not only by Mn2+, Ca2+ and Mg2+, but also by spermine, spermidine, lysyl-lysine, ethylenediamine and other diaminoalkanes, and by a range of basic proteins and peptides, including clupeine, histone, polylysine, ribonuclease, pancreatic trypsin inhibitor, cytochrome c, melittin, avidin and myelin basic protein. Both N-acetyl lactosamine synthetase and lactose synthetase activities were enhanced. A basic protein fraction was isolated from bovine milk and shown to activate galactosyltransferase at low concentrations. The polyanions ATP, casein, chondroitin sulphate and heparin reversed the activation of galactosyltransferase by several of the above substances. Galactosyltransferase, assayed as a lactose synthetase, showed a 10-fold greater affinity for glucose when Mn2+ ions were replaced by clupeine or by ribonuclease as cationic activator. Evidence was obtained for the presence of an endogenous cationic activator in solubilized Golgi membrane preparations which evoked a similar low apparent Km,glucose. The findings are discussed in the light of cationic activations of glycosyltransferases generally, of the porous nature of the Golgi membrane, and of the unlikelihood of bivalent metal ions being the physiological activators of galactosyltransferase. It is suggested that the natural cationic activator of lactose synthetase may be a secretory protein acting in a manner analogous to the enzyme's activation by alpha-lactalbumin. A scheme is proposed for the two-stage synthesis of lactose and phosphorylation of casein within the cell, to accommodate the apparent incompatibility of these two processes. PMID- 3101668 TI - An active-site titrant for human tissue-type plasminogen activator. AB - The reaction of recombinant tissue-type plasminogen activator with the inverse substrate 4-amidino-2-nitrophenyl 4'-anisate results in the rapid release of the chromogen 4-amidino-2-nitrophenol and the accumulation of the relatively stable 4 anisoyl-enzyme. Spectrophotometric monitoring of the reaction enables the operational molarity of the enzyme to be determined. PMID- 3101669 TI - Activation of hepatic glycogen phosphorylase b in vivo by sodium sulphate in normal (Wistar) and phosphorylase b kinase-deficient (gsd/gsd) rats. AB - Sulphate ions have been known for some years to enhance the activity of hepatic glycogen phosphorylase b in vitro. Here we report that intravenous injections of 4.92 mmol of Na2SO4/kg body wt. to rats induced marked hepatic glycogenolysis in vivo, accompanied by polyuria, glycosuria and a mild hyperglycaemia. These effects were observed both in normal (Wistar) rats and in gsd/gsd rats that lacked hepatic phosphorylase kinase. In both rat strains the activity of glycogen phosphorylase in liver extracts was enhanced by pretreatment of the animals with Na2SO4, but in phosphorylase kinase-deficient livers the enhancement was solely in phosphorylase b activity, whereas both the a and b forms of the enzyme were activated in normal livers. Hepatic glycogenolysis was also induced by perfusing rat livers, both normal and gsd/gsd, with 25 mM-Na2SO4. Under these conditions both the rat strains showed only enhanced activities of glycogen phosphorylase b. This suggested that the increased activity of phosphorylase a in the extracts of normal livers after Na2SO4 administration in vivo was due to a hormonally mediated conversion of the b form into the a form. The activation of glycogen phosphorylase b was stable to dilution and appeared to be due to a long-lasting structural change in the enzyme or very tight binding of an activator. PMID- 3101670 TI - Erythrocyte nucleoside and sugar transport. Endo-beta-galactosidase and endoglycosidase-F digestion of partially purified human and pig transporter proteins. AB - Nucleoside- and glucose-transport proteins isolated from human erythrocyte membranes were photoaffinity-labelled with [3H]nitrobenzylthioinosine and [3H]cytochalasin B, respectively, and subjected to endo-beta-galactosidase or endoglycosidase-F digestion. Without enzyme treatment the two radiolabelled transporters migrated on SDS/polyacrylamide gels with the same apparent Mr (average) of 55,000. Apparent Mr (average) values after endo-beta-galactosidase digestion were 47,000 and 48,000 for the nucleoside and glucose transporters respectively, and 44,000 and 45,000 respectively after endoglycosidase-F digestion. In contrast, endo-beta-galactosidase had no effect on the electrophoretic mobility of the nucleoside transporter isolated from pig erythrocytes. This transport system exhibited a higher Mr than the human protein, endoglycosidase-F treatment decreasing its apparent Mr (average) from 64,000 to 57,000. It is concluded that the human and pig erythrocyte nucleoside transporters are glycoproteins containing N-linked oligosaccharide. The data provide evidence of substantial carbohydrate and polypeptide differences between the human and pig erythrocyte nucleoside transporters, but evidence of molecular similarities between the human erythrocyte nucleoside and glucose transporters. PMID- 3101671 TI - Oxidation and enzyme-activated irreversible inhibition of rat liver monoamine oxidase-B by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). AB - The compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces symptoms resembling Parkinson's disease in humans, acts both as a substrate and an enzyme-activated irreversible inhibitor of the B-form of monoamine oxidase from rat liver. Analysis of the inhibitory process showed the compound to be considerably more efficient as a substrate than as an irreversible inhibitor, with about 17000 mol of product being formed per mol of enzyme inactivated. The half-time of the inhibitory process was about 22 min. With the A-form of the enzyme, the compound had a lower Km value and a considerably lower maximum velocity than the corresponding values obtained with the B-form. Under the conditions used in the present work the inhibition of the A-form of the enzyme was largely reversible. PMID- 3101672 TI - Platelet-activating factor (PAF-acether) induces high- and low-affinity binding of fibrinogen to human platelets via independent mechanisms. AB - When human platelets are incubated with 500 nM-PAF-acether (platelet-activating factor. 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) under equilibrium conditions (60 min, 22 degrees C, non-stirred suspensions), two classes of fibrinogen binding sites are exposed: one class with a high affinity [Kd (7.2 +/- 2.1) X 10(-8) M, 2367 +/- 485 sites/platelet, n = 9] and one class with a low affinity [Kd (5.9 +/- 2.4) X 10(-7) M, 26972 +/- 8267 sites/platelet]. Preincubation with inhibitors of cyclo-oxygenase (acetylsalicylic acid, indomethacin) or thromboxane synthetase (UK 38.485) completely abolishes high affinity binding, leaving low-affinity binding unchanged. In contrast, ADP scavengers (phosphocreatine/creatine kinase or phosphoenol pyruvate/pyruvate kinase) completely prevent low-affinity binding, leaving high-affinity binding unaltered. Initial binding studies (2-10 min incubation) confirm these findings with a major part of the binding being sensitive to ADP scavengers, a minor part sensitive to indomethacin and complete blockade with both inhibitors. Increasing the temperature to 37 degrees C decreases the number of low affinity-binding sites 6-fold without changing high-affinity binding. Aggregation, measured as the rate of single platelet disappearance, then depends on high-affinity binding at 10 nM-fibrinogen or less, whereas at 100 nM-fibrinogen or more low-affinity binding becomes predominant. These findings point at considerable platelet activation during binding experiments. However, arachidonate metabolism [( 3H]arachidonate mobilization and thromboxane synthesis) and secretion [( 14C]serotonin and beta-thromboglobulin) are about 10% or less of the amounts found under optimal conditions (5 units of thrombin/ml 37 degrees C, stirring). We conclude that PAF-acether induces little platelet activation under binding conditions. The amounts of thromboxane A2 and secreted ADP, however, are sufficient for initiating high- and low-affinity fibrinogen binding via mutually independent mechanisms. PMID- 3101675 TI - Biological activity of polychlorinated biphenyls related to conformational structure. PMID- 3101674 TI - NADPH: cytochrome P-450 reductase in olfactory epithelium. Relevance to cytochrome P-450-dependent reactions. AB - The presence of a very active cytochrome P-450-dependent drug-metabolizing system in the olfactory epithelium has been confirmed by using 7-ethoxycoumarin, 7 ethoxyresorufin, hexobarbitone and aniline as substrates, and the reasons for the marked activity of the cytochrome P-450 in this tissue have been investigated. The spectral interaction of hexobarbitone and aniline with hepatic and olfactory microsomes has been examined. By this criterion there was no evidence for marked differences in the spin state of the cytochromes of the two tissues, or for the olfactory epithelium containing a greater amount of cytochrome capable of binding hexobarbitone, a very actively metabolized substrate. Rates of NADPH and NADH: cytochrome c reductase activity were found to be higher in the olfactory epithelium than in the liver, and direct evidence was obtained for a greater amount of the NADPH-dependent flavoprotein in the olfactory microsomes. Investigation of male rats and male and female mice, as well as male hamsters, demonstrated that, in all cases, the cytochrome P-450 levels of the olfactory epithelium were lower than those of the liver, while the 7-ethoxycoumarin de ethylase and NADPH:cytochrome c reductase activities were higher. A correlation was found between 7-ethoxycoumarin de-ethylase and NADPH:cytochrome c reductase activities for both tissues in all species examined. The ratio of reductase to cytochrome P-450 was found to be considerably higher in the olfactory epithelium (1:2-1:3) than in the liver (1:11-1:15), regardless of the species examined, suggesting that facilitated electron flow may contribute significantly to the cytochrome P-450 catalytic turnover in the olfactory tissue. PMID- 3101673 TI - The egasyn gene affects the processing of oligosaccharides of lysosomal beta glucuronidase in liver. AB - The accumulation of the relatively large amounts of beta-glucuronidase in microsomal fractions of normal mice depends on formation of complexes with the protein egasyn. Unexpectedly, it was found that the egasyn gene also affects the processing of beta-glucuronidase, which is segregated to lysosomes. In egasyn positive mice lysosomal beta-glucuronidase from liver has a mean pI of 5.9 with a minor proportion at pI 5.4, whereas in egasyn-negative mice the proportion of the two lysosomal forms is reversed. Combined experiments measuring susceptibility to neuraminidase and to endoglycosidase H and specific binding to Ricinus communis lectin-agarose columns showed that the alterations in isoelectric point were associated with a decrease in complex oligosaccharides of lysosomal beta glucuronidase in egasyn-positive mice. Since this alteration occurs not only in a congenic strain carrying the Eg0 gene but also in several other inbred strains that are homozygous for this gene, it is considered to be a genuine effect of the Eg gene rather than other genes that might regulate oligosaccharide processing. Also, the alteration is likely to be a result of direct physical interaction of the egasyn protein and lysosomal beta-glucuronidase, since a second lysosomal enzyme, beta-galactosidase, which does not form complexes with egasyn, is unaffected. The results suggest a model in which egasyn not only causes accumulation of beta-glucuronidase in the microsomal compartment but also acts upon the precursor to lysosomal beta-glucuronidase to alter its interaction with trans-Golgi-apparatus processing enzymes. PMID- 3101676 TI - Chloro-substituent sites and probability of co-planarity in polychlorinated biphenyls in determining uroporphyrin formation in cultured liver cells. PMID- 3101677 TI - Absolute configuration of the hydroxyeicosatetraenoic acids (HETEs) formed during catalytic oxygenation of arachidonic acid by microsomal cytochrome P-450. AB - Rat liver microsomal cytochrome P-450 catalyzes the NADPH dependent metabolism of arachidonic acid to six regioisomeric cis,trans-dienols. The 12(R) hydroxyeicosatetraenoic acid is generated with a high degree of enantioselectivity while the remaining regioisomers are produced as nearly racemic mixtures. PMID- 3101678 TI - Chromosomal localization of the gene for a human galactosyltransferase (GT-1). AB - The gene for human galactosyltransferase (EC 2.4.1.22) has been localized to the short arm of chromosome 9 by in situ hybridization to human metaphase chromosomes of a 985 bp cDNA probe for the gene. PMID- 3101679 TI - Glucose 6-phosphate plays a central role in the activation of glycogen synthase by glucose in hepatocytes. AB - The state of activation of glycogen synthase enhanced by glucose, other sugars and gluconeogenic precursors shows a strong positive correlation with the intracellular concentrations of glucose 6-P when ATP concentrations remain constant. The concentrations of glucose 6-P achieved upon incubation of hepatocytes with glucose plus mannoheptulose, an inhibitor of glucokinase and hexokinase, were lower than those found when the incubation was carried out with glucose alone. Under these conditions, in keeping with the decrease in glucose 6 P, the activation of glycogen synthase by glucose was also impaired. On the other hand the inactivation of glycogen phosphorylase was not altered in the presence of mannoheptulose. PMID- 3101680 TI - Influence of 1,25-hydroxyvitamin D3 on cytosolic free calcium concentrations. AB - Using isolated cartilage cells from the epiphyseal growth plate of rachitic chicks and utilizing the fluorescence indicator quin2 for measurements of cytosolic free calcium, it has been possible to demonstrate that 1,25 dihydroxyvitamin D3 regulates the concentrations of cytosolic free calcium. The reduction in cytosolic free calcium is associated with inhibition of the activity of alkaline phosphatase. As several hours are required before an effect on cytosolic free calcium can be observed in the cells, it is suggested that the action is dependent on genomic interactions. PMID- 3101681 TI - Induction of phage-like particles from a pathogenic strain of Vibrio parahaemolyticus by mitomycin C. AB - A rapid drop of absorbance of cell suspensions due to cell lysis was observed midway in cell growth of a pathogenic strain, Vibrio parahaemolyticus WP1, when the cells were incubated in a growth medium containing mitomycin C. We succeeded in isolating phage-like particles from the cell lysate, but not from that of the non-pathogenic strain, WP28. The purified particle has a clear-cut envelope and is hexagonal in shape with no tail. The size of particles is about 65 millimicrons on the diagonal and about 250 S. The particles contained one kind of protein of 45,000 dalton. PMID- 3101682 TI - Degradation of glomerular basement membrane by a neutral metalloproteinase(s) present in glomeruli isolated from normal rat kidney. AB - Incubation of glomerular homogenates (200 micrograms protein) with glomerular basement membrane (GBM, 30-35 micrograms hydroxyproline) at pH 7.5 for 36 h at 37 degrees C resulted in significant GBM degradation as measured by hydroxyproline release (40 +/- 6%, n = 17). GBM degradation increased with increasing incubation time (12-48 h) and glomerular protein concentration (50-250 micrograms). GBM degradation was not significantly decreased by inhibitors of serine or cysteine proteinases or the inhibitor of bacterial metalloproteinases, phosphoramidon. In contrast GBM degradation by glomerular homogenates was markedly inhibited by the metal chelators 10mM EDTA (-95 +/- 3%, n = 7) and 2mM 1,10-phenanthroline (-96 +/ 2%, n = 4). Preincubation of glomerular homogenates with trypsin (followed by soya bean trypsin inhibitor) markedly stimulated GBM degradation (+103 +/- 20%, n = 11). These results document the presence of a GBM-degrading, neutral metalloproteinase(s) in glomeruli suggesting an important role for this enzyme in glomerular pathophysiology. PMID- 3101683 TI - Purification and characterization of glyoxalase I from Pseudomonas putida. AB - Glyoxalase I was purified to apparent homogeneity from Pseudomonas putida. The enzyme was a monomer with a molecular weight of 20,000. The enzyme was most active at pH 8.0. The Km values for methylglyoxal and 4,5-dioxovale-rate are 3.5 mM and 1.2 mM, respectively. Contrary to the case of eukaryotic enzymes, chelating agents showed little inhibitory effects on the enzyme activity. Among the metal ions tested, Zn++ specifically and completely inhibited the activity of the enzyme at a millimolar level. The properties of bacterial glyoxalase I were quite different from mammalian and yeast enzymes. PMID- 3101684 TI - A highly sensitive chromogenic microtiter plate assay for plasminogen activators which quantitatively discriminates between the urokinase and tissue-type activators. AB - A simple and highly sensitive chromogenic microtiter plate assay for plasminogen activators is described. The assay is based on plasmin cleavage of the synthetic tripeptide plasmin substrate H-D-norleucyl-hexahydrotyrosyl-lysine p nitroaniline, which yields the yellow chromophore p-nitroanilide. Production of the latter compound is then quantitated spectrophotometrically at 405 nm on an ELISA plate reader. Linearity of the assay can be achieved over at least four orders of magnitude in a single experiment (0.01-100 milliPloug units) with appropriate incubation times. Capitalizing on tissue-type plasminogen activator's dependence on fibrin for enzymatic activity, the selective use of soluble fibrin products allows discrimination between urokinase and tissue-type activator. The utility of this aspect of the assay for the analysis of complex samples containing both types of plasminogen activators is demonstrated. PMID- 3101685 TI - Phosphorylation by protein kinase C of a synthetic heptapeptide bearing a lysine residue on the C terminal side of serine. AB - A peptide, Ala-Ser-Gly-Ser-Phe-Lys-Leu, which corresponds to Ala103-Leu109 of Hl histone, was synthesized and tested as substrate for protein kinase C. The serine residue at position 4 was phosphorylated specifically. Another peptide lacking the lysine at position 6 was not phosphorylated by the same enzyme, indicating the importance of that basic residue as the recognition site for protein kinase C. PMID- 3101686 TI - Identification of two types of protein immunochemically related to urinary urokinase occurring in human plasma. AB - Plasma urokinase, a plasminogen activator immunochemically related to urinary urokinase (UK), was removed from human plasma (3.5 ng/ml) by immuno-depletion with antibodies raised against UK. The remaining plasminogen activator activity of the depleted plasma could not be inhibited by anti-UK antibodies and a sensitive ELISA for UK did not detect any UK levels that were higher than the background of the assay (0.1 ng/ml). However, when the depleted plasma was subjected to SDS-PAGE, substantial amounts of protein were found hereafter around 110 and 46 kD which now gave a positive reaction in the ELISA (35-350 ng/ml plasma). From these observations it is concluded that in human plasma two types of UK-related protein occur: Type I, among which the plasma urokinase, has antigenic determinants which are directly accessible to the anti-UK antibodies, Type II has determinants in a latent form. The function of the 110 kD type-II protein is that of a plasminogen activator; that of the 46 kD protein is not yet clear. PMID- 3101687 TI - L-proline uptake in human fibroblasts: evidence for a high-affinity system in addition to system A. AB - Proline uptake was studied in human skin fibroblasts by simultaneous running of kinetic and inhibition experiments on the same cell lines. Two systems for proline uptake were shown: a high-affinity system not inhibited by alpha (methylamino)isobutyric acid and a low affinity system inhibited by this amino acid (i.e. system A). These results appear to be of interest, firstly because up till now, system A was considered preferable for proline uptake in human fibroblasts, and secondly because they illustrate the need for combined inhibition and kinetic studies of amino acid uptake, especially when the substrate concentration range used and the respective Km of the systems do not allow their detection by kinetic analysis alone. Furthermore, this high-affinity system may have major physiological implications. PMID- 3101688 TI - Unmasking of arachidonate-induced insulin release by removal of extracellular calcium. Arachidonic acid mobilizes cellular calcium in rat islets of Langerhans. AB - Exogenous arachidonic acid does not stimulate insulin release in Ca++-containing medium, but a potent effect was unmasked by extracellular Ca++ depletion. This secretion met several criteria of exocytotic release. It did not require the oxygenation of arachidonate or its esterification into islet membranes, but was potentiated by the presence of 16.7 mM glucose such that 33 microM arachidonate could reverse the inhibitory effects of extracellular Ca++ removal on glucose induced insulin secretion. Arachidonic acid alone stimulated a rise in intracellular Ca++ concentrations in dispersed islet cells (measured by the fura 2 technique) equal to that induced by 16.7 mM glucose in normal medium. Arachidonic acid may be a critical coupling signal in normal islets. PMID- 3101689 TI - Involvement of reactive oxygen species in the oxidation of tyrosine and dopa to melanin and in skin tanning. AB - The role of reactive oxygen (1O2 and O2-.) in skin photosensitization and tanning reaction has been examined. Riboflavin (RF), hematoporphyrin (HP), 3 carbethoxypsoralen (3-CP), and 8-methoxypsoralen (8-MOP), upon photoexcitation under aerobic conditions, produced singlet O2 (1O2). RF, 3-CP, and 8-MOP also produced superoxide anion (O2-.). Reactive O2 produced by photosensitized RF, 3 CP, and 8-MOP was found to oxidize tyrosine and dopa to dopachrome and subsequently their conversion to melanin. HP did not oxidize tyrosine to dopachrome, and 3-CP and RF revealed substantial oxidation of tyrosine. Dopa was oxidized to dopachrome and subsequently to melanin by all photosensitizers tested at a variable rate as follows: RF greater than 3-CP greater than HPD greater than 8-MOP. UVA alone and to a lesser extent UVB also produced 1O2 which induced the oxidation of tyrosine and dopa to dopachrome and subsequently to melanin. The production of dopachrome was higher with dopa compared to tyrosine under all irradiation conditions. These observations appear to have relevance to the O2 requiring immediate tanning reaction of the skin stimulated by solar radiation and in the induction of skin photosensitization. PMID- 3101690 TI - NIH 3T3 cells transfected with human tumor DNA lose the transformed phenotype when treated with swainsonine. AB - Phenotypic expression of transformation was inhibited by swainsonine at concentrations which affect the late stages of glycoprotein processing but not growth of cells. In the presence of swainsonine, NIH 3T3 fibroblasts transfected with human tumor DNA (al-l) no longer grew in soft agar or expressed complex type oligosaccharides characteristic of transformed cells. Thus, it appears that glycoproteins with fully processed oligosaccharides are necessary for the maintenance of the transformed phenotype in these cells. PMID- 3101691 TI - The study of diabetic cataractogenesis in the intact rabbit lens by deuterium NMR spectroscopy. AB - The polyol pathway has been implicated in the process of diabetic cataractogenesis. We report the use of deuterium (2H) spectroscopy for dynamically monitoring the polyol and glycolytic pathways in the single intact rabbit lens. Using 2H labeled C-1 D-glucose, the formation of sorbitol from glucose and the metabolism of sorbitol to fructose was dynamically monitored at 5.5 mM and 35.5 mM glucose concentrations. The accumulation of sorbitol at 35.5 mM glucose concentration was prevented by the inhibition of aldose reductase using an inhibitor (Sorbinil). 2H spectra were obtained in short acquisition times because of the short T1's of deuterated metabolites. A further advantage of 2H spectroscopy is that the natural abundance resonance of water (HDO) can be used as an internal reference standard. These findings confirm previous studies and demonstrate for the first time by NMR spectroscopy activity in the polyol pathway at low glucose concentrations. PMID- 3101692 TI - Nonradioactive hybridization probes prepared by the reaction of biotin hydrazide with DNA. AB - A novel one-step chemical method has been developed for the introduction of biotin into nucleic acids for non-isotopic hybridization. The method is based on the interaction of biotin hydrazide with unpaired cytosine residues. The interaction is catalyzed by sodium bisulfite with an optimum at a buffered pH of about 4.5. The reaction reached its maximum after 24 h incubation at a biotin hydrazide concentration of 10 mg/ml. Using streptavidin-alkaline phosphatase conjugates, the limits for detecting the biotinylated probe, either adsorbed directly to nitrocellulose or hybridized to filter-bound target DNA, were 0.3 and 0.9 pg, respectively. The salience of the approach described here over previously used biotin derivatives is that it is quick (one-step), simple and does not involve any enzymatic or instrument-mediated step to introduce the reporter moiety. In addition, other low- and high-molecular-weight hydrazides (e.g. fluorescent or enzyme hydrazides) can serve as the reporter group. The same procedure may be employed for the single-step biotinylation of free cytidine. PMID- 3101693 TI - Evidence against a possible involvement of the serine, and thiol proteases in the exocytotic mechanism of catecholamine secretion in cultured bovine adrenal medullary cells. AB - The effects of protease inhibitors on the secretion of catecholamines were studied in cultured bovine adrenal medullary cells. Although the inhibitors of serine proteases could inhibit the carbamylcholine-induced secretion, they failed to inhibit the secretion evoked by either high K+ or A23187. The thiol protease inhibitor had no effect on the secretion. These results therefore seem to indicate that the serine protease inhibitors may inhibit the receptor-mediated secretion probably through their effects on the plasma membrane, thus suggesting that a possible involvement of the serine, and thiol proteases in exocytosis may be unlikely. PMID- 3101694 TI - Digestion of repair sites in rat liver DNA by endogenous nucleases. AB - The proportion of sheared rat liver DNA recovered from benzoylated DEAE-cellulose in the final stage following stepwise elution with NaCl and caffeine solutions was dependent upon the DNA isolation procedure. An increase in the proportion of DNA containing single stranded regions, consequent upon delay or addition of Mg2+ prior to phenol extraction, suggested nuclease mediated degradation. Administration of methyl methanesulphonate to rats resulted in a consistent proportional increase in the caffeine-eluted fraction. The results of caffeine gradient elution of control and alkylated DNA from benzoylated DEAE-cellulose were consistent with repair-associated single stranded regions being substrates for endogenous single strand-specific exonucleases. PMID- 3101695 TI - Genes and proteins in immunity. PMID- 3101696 TI - Molecular events during the onset and maturation of the antibody response. PMID- 3101698 TI - Paradigm regained: similarities and differences between T cell receptor and immunoglobulin genes. PMID- 3101697 TI - T cell receptors in the thymus. PMID- 3101699 TI - Molecular genetics of the fourth component of human complement. AB - The fourth component of human complement is encoded by two separate, but closely linked, loci, C4A and C4B, that have been positioned within the class III region of the HLA complex. While the two isotypes vary by only six amino acid residues, they differ significantly in haemolytic activity. Both loci are considerably polymorphic and this may be biologically relevant to ensure interaction with a wide range of pathogens. The number of C4 genes expressed is polymorphic as null alleles, total deficiency and duplication has been shown based on protein studies. Southern analysis of 24 different haplotypes with either C4A or C4B null alleles using the C4 probes showed that three of the null alleles were due to deleted genes but the majority appeared normal. A cosmid library was prepared from DNA of one of the deleted haplotypes and the region of deletion analysed by restriction mapping. PMID- 3101700 TI - Regulation of complement gene expression. AB - The availability of molecular probes for approximately half of the 20 known complement genes now permits a detailed examination of the regulation of complement expression in liver and at extrahepatic sites in tissue macrophages. Primary cell culture, cell lines and cells transfected with DNA bearing complement genes have been used in this analysis. Pretranslational regulation of complement production has been induced by well defined cytokines such as interleukin-1 and gamma-interferon, as well as directly by endotoxin. The effect of those agents on complement genes is tissue and species specific and is developmentally regulated. These data form the basis for the elucidation of the genomic structural requirements for regulation of inflammation and, by extension, specific immune responsiveness. PMID- 3101701 TI - C2 and factor B: structure and genetics. AB - Complement components C2 and factor B are novel types of serine protease that are encoded by single loci in the major histocompatibility complex on human chromosome 6. The two proteins share 39% homology, or 50% taking into account conservative amino acid replacements. The catalytic chains, C2a (509 residues) and Bb (505 residues) show homology in their C-terminal domains to the catalytic polypeptides of other serine proteases. The non-catalytic chains, C2b (223 residues) and Ba (234 residues) both contain three tandem repeats of approx. 60 amino acids each, which are homologous to the repeats in C4b-binding protein and factor H, and also the repeats in the non-complement protein beta 2-glycoprotein I. Molecular mapping and DNA sequence analysis has shown that the factor B gene is 6 kb in length and contains 18 exons, while the C2 gene is 18 kb in length; 425 bp separates the 3' end of the C2 gene from the 5' end of the factor B gene. C2 and factor B are polymorphic and structural variants have been detected at the protein level by differences in charge. The degree of polymorphism at the factor B locus has been defined by DNA sequence analysis of the two common alleles F and S. In addition restriction fragment length polymorphisms have been detected in the C2 gene. These DNA polymorphisms subdivide the common allelic variant of C2 (C2C) and reveal that there is much greater variability at the C2 locus than that detected by protein typing. PMID- 3101702 TI - Lysosomal membrane glycoproteins: properties of LAMP-1 and LAMP-2. AB - Several properties of the lysosomal membrane glycoproteins LAMP-1 and LAMP-2 have been analysed. Each molecule was strongly associated with lysosome membranes and was extracted only in the presence of detergent. Studies of the biosynthesis and processing of the glycoproteins showed that each contained a polypeptide core of approx. 43,000 Da as identified by use of tunicamycin and endoglycosidase H. Nascent glycoproteins pulse-labelled for 5 min with [35S]methionine were approx. 92,000 Da. These precursor molecules were processed in 30 min to highly heterogeneous mature glycoproteins of approx. 110,000 Da(LAMP-1) and 105,000 Da(LAMP-2). Concomitant with the increase in apparent Mr the molecules became endoglycosidase H resistant and acquired sialic acid residues, indicating that they were converted to complex-type oligosaccharides. The final maturation of the glycoproteins was blocked by monensin. Immunohistochemical analysis of tissues from Balb/c and Beige/J mice showed that the molecules were present on many types of cells, consistent with their presence in lysosomes. The patterns of tissue expression of LAMP-1 and LAMP-2 in the two mouse strains were the same except that the intensity of staining of LAMP-2 was less than that of LAMP-1. LAMP-2, but not LAMP-1, gave a decreased immunofluorescent staining intensity in transformed HaNIH as compared with NIH/3T3 cells. The marked similarities between the LAMP proteins raise the consideration of common functions, possibly associated with the high oligosaccharide content of the molecules. PMID- 3101703 TI - Purification and properties of rat kidney UDP-glucuronosyltransferase. AB - Rat kidney microsomes catalysed the glucuronidation of 1-naphthol, 4-nitrophenol, bilirubin and beta-estradiol. Unlike rat hepatic microsomes, UDP glucuronosyltransferase activity towards morphine and testosterone was not detectable. Treatment of rats with beta-naphthoflavone resulted in a 3-fold induction of renal UDPGT activity towards 1-naphthol, 4-nitrophenol and phenol, and a 2-fold induction of bilirubin and beta-estradiol glucuronidation. No induction of renal UDPGT was observed after phenobarbital treatment, but renal bilirubin UDPGT activity was specifically induced after treatment of rats with clofibrate. UDPGT activity was purified from rat kidney by a combination of ion exchange chromatography, gel filtration and affinity chromatography on UDP hexanolamine Sepharose. One major protein-staining polypeptide was observed on silver-stained SDS-polyacrylamide gels, of molecular weight 55,000 Da, and a minor band of 54,000 Da was also present. Indeed, immunoblot analysis of purified renal UDPGTs with anti-rat liver UDPGT antibodies revealed two immuno-reactive polypeptides of molecular weight 55,000 and 54,000 Da. The highly purified preparations catalysed the glucuronidation of 1-naphthol and bilirubin. Glucuronidation of bilirubin by purified renal UDPGT preparations required the presence of phospholipid, the activity being further enhanced by incubation with rat lung microsomes. The data presented indicate that two UDPGT isoenzymes have been copurified. PMID- 3101704 TI - On the mechanism of antithrombotic action of flavonoids. AB - Flavonols (quercetin and rutin) and flavanes (cyanidol and meciadonol) were studied for their effect on non-enzymatic lipid peroxidation, lipoxygenase and cyclo-oxygenase activities, binding to albumin and platelet membranes. These biochemical properties of four flavonoids were compared with respect to their antithrombotic action in vivo and their efficacy at influencing the platelet endothelium interaction in vitro. All four flavonoids inhibited the ascorbate stimulated formation of malondialdehyde by boiled rat liver microsomes (quercetin greater than rutin approximately cyanidol approximately meciadonol) and inhibited platelet lipoxygenase activity (quercetin greater than cyanidol greater than meciadonol greater than rutin) whereas only flavonols, but not flavanes, stimulated cyclo-oxygenase and were bound to platelet membranes. The same two flavonols dispersed platelet thrombi which were adhering to the rabbit aortic endothelium in vitro (EC50 for quercetin was 80 nM and for rutin 500 nM) and prevented platelets from aggregation over blood-superfused collagen strip in vivo (ED50 for quercetin was 5 nmol/kg and for rutin 33 nmol/kg i.v.). Cyanidol and meciadonol were not effective as anti-thrombotic agents. It is concluded that activated platelets adhering to vascular endothelium generate lipid peroxides and oxygen-free radicals which inhibit endothelial biosynthesis of prostacyclin and destroy endothelium-derived relaxing factor (EDRF). Flavonols are anti-thrombotic because they are selectively bound to mural platelet thrombi and owing to their free radical scavenging properties resuscitate biosynthesis and action of endothelial prostacyclin and EDRF. Thus, flavonols release the thrombolytic and vasoprotective endothelial mediators only in these vascular segments which are covered by a carpet of aggregating platelets. PMID- 3101705 TI - Stimulation of prostaglandin production by (2E,6Z,10E)-7-hydroxymethyl-3,11,15 trimethyl-2,6,10,14-++ +hexadecatetrae n-1-ol (plaunotol), a new anti-ulcer drug, in vitro and in vivo. AB - Plaunotol [(2E,6Z,10E)-7-hydroxymethyl-3,11,15-trimethyl-2,6,10,14- hexadecatetraen-1-ol], a new anti-ulcer drug, was investigated for its effect on prostaglandin (PG) production. In cultured cells of 3T6 fibroblasts, plaunotol and its main metabolite (1-carboxylic plaunotol) at concentrations of 10-100 microM increased PGE2 and PGI2 production 2- to 4-fold. These compounds increased the release of radioactive arachidonic acid from [14C]arachidonic acid prelabeled 3T6 fibroblast cells 2-fold at 30 microM, and this increase was inhibited by addition of mepacrine, a phospholipase inhibitor. Plaunotol and its main metabolite had no effect on PG cyclooxygenase activity. These results indicate that plaunotol and its main metabolite stimulate PG production by activating cellular phospholipase. In gastric-mucosa slices, PGE2 and PGI2 production was increased significantly either by oral administration of plaunotol to rats at a dose of 300 mg/kg or by addition of the main metabolite to the incubation medium. All these results suggest that plaunotol increases the PG levels in gastric mucosa by stimulating the PG biosynthesis, particularly the cellular phospholipase activity. The increased levels of PG may participate in the anti ulcer activity of plaunotol. PMID- 3101706 TI - Changes in cell surface antigen expression on human articular chondrocytes induced by gamma-interferon. Induction of Ia antigens. AB - Ia antigens (class II HLA molecules) have been detected on cells eluted from affected human cartilage in certain disease states, but not on normal cartilage cells. Because the presence of Ia antigens on chondrocytes may play an important role in rheumatic diseases, we investigated the induction of these molecules by gamma-interferon (gamma-IFN), a potent Ia-inducing lymphokine. Human articular chondrocytes were incubated with recombinant gamma-IFN, and the expression of Ia antigens was studied by cell sorter analysis, using a panel of reagents that detect monomorphic and polymorphic specificities of the DR and DQ Ia antigen families. While the induction of DR antigens, including polymorphic DR specificities, was readily obtained with gamma-IFN (50-95% positive cells), DQ antigens were negative or were displayed only on a lower percentage of chondrocytes (5-60%). In addition, incubation with gamma-IFN led to an increased expression of HLA class I antigens. The expression of various other surface markers either remained unchanged (as in 4F2 and BA-2) or showed tendencies toward decreased percentages (as in 83c2) or increased percentages (as in M phi R 17). No apparent change in cell morphology or growth pattern was observed. PMID- 3101707 TI - Pharmacokinetics of ciprofloxacin. 2nd communication: distribution to and elimination from tissues and organs following single or repeated administration of [14C]ciprofloxacin in albino rats. AB - 1-Cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-[U-14C]piperazinyl)-3-quinoline carboxylic acid (ciprofloxacin, Bay o 9867; designated tradename: Ciprobay) was administered to male and to pregnant albino rats with single intravenous or oral doses of 5 or 10 mg/kg body weight and with repeated oral doses of 5 mg/kg (7 consecutive daily administrations to male rats). Following a single intravenous administration the [14C]ciprofloxacin related radioactivity was distributed rapidly and differentiated to the body. Compared to plasma high concentrations were determined in kidney, liver, skeleton muscle, pancreas, testes and cartilage, low concentrations occurred in brain and adipose tissue. In some selected tissues radioactivity was largely due to unchanged [14C]ciprofloxacin (57% to 100%). A good penetration of total radioactivity into tissues and organs with a similar distribution pattern as detected after intravenous dosing also occurred after a single oral administration. Highest concentrations were determined 1 h after dosing. Compared to plasma most tissues and organs showed higher concentrations and higher AUC-values. For brain and eye low values were determined. Compared to plasma a longer mean residence time of radioactivity was calculated for brain, eye, eye-wall, testes and blood cells. 6 d after single administration the radioactive residues in the body exclusive gastrointestinal tract amounted to less than 0.1% of the dose. Following a seven-day treatment the distribution pattern of total radioactivity in the body did not differ essentially from that after single dosing. Compared to single dosing AUC-values higher by the factor 2 to 4 were calculated after repeated administration for plasma and most of the tissues and organs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101708 TI - On steroid-saving drug combinations in carrageenin paw edema and adjuvant arthritis. AB - Sequential potentiation of antiinflammatory activity of dexamethasone was obtained by co-administration of diclofenac-Na (and indomethacin), but not of phenylbutazone and, apparently, of acetylsalicylic acid (ASA) in the carrageenin rat paw edema. In the adjuvant arthritic rat, additive effects were only seen. Co administration of ASA-like cyclooxygenase inhibitors with lipoxygenase and/or phospholipase A2 inhibitors partly gave also overadditive antiinflammatory effects in the carrageenin rat paw edema. However, phenylbutazone failed in this respect, possibly due to its different mode of action. Admixture of ascorbic acid rather decreased than increased antiinflammatory activity of cyclooxygenase inhibitors and drug combinations except ASA, the effectivity of which was practically not changed. PMID- 3101710 TI - [Hypotensive, antianginal action and pharmacokinetics of glyceryl-1-nitrate in rats and dogs]. AB - The antianginal and hypotensive activity and the pharmacokinetic properties of glyceryl 1-nitrate (G-1-N) were examined in the rat and in the dog. The level and duration of antianginal and hypotensive activity were the same after single or repeated oral dosage of G-1-N to the anaesthetized rat. The haemodynamic activity of intravenously administered G-1-N in the anaesthetized and thoracotomized dog was dose-dependent. A bolus injection of G-1-N or glyceryl trinitrate (GTN, Nitro Mack) antagonized the cardiovascular activity of intravenously injected dihydroergotamine (DHE) in the anaesthetized and thoracotomized dog. The bioavailability of G-1-N in the rat and in the dog is practically 100%. After intravenous or oral administration to the rat the concentrations of G-1-N in the walls of the vena cava caudalis were markedly higher and in the aorta abdominalis somewhat higher than in the blood or in the other organs examined. G-1-N was eliminated more slowly from the walls of the animals veins than from the walls of the aorta abdominalis or from the blood. PMID- 3101709 TI - [Interferon-gamma in the therapy of chronic polyarthritis]. AB - The paper gives a survey of the studies with interferon-gamma and the actual status of the clinical trials with this substance concerning rheumatoid arthritis (RA). About 60% of the patients with RA respond to the therapy. In the initial therapy which covers a time of 2 to 6 weeks 50 micrograms (in case of side effects 20 or 10 micrograms) should be given 3 to 7 times per week by the subcutaneous route. When the disease is improved, the maintenance therapy starts. According to the patient's status, the dosage frequency and the dose have to be reduced to sustain the effect. PMID- 3101711 TI - Estrogenic activities of estradiol enantate and ethinylestradiol compared at a clinical level. AB - Healthy menopausic women accepted to receive two consecutive estrogenic treatments: 1. ethinylestradiol 0.030 mg/d p.o. during 21 days; 2. a single dose of estradiol enantate (estra-1,3,5(10)-triene-3-ol-17 beta-heptanoate, one of the components of Perlutal or Topasel) 10 mg i.m. Both treatments were separated by a 1-month wash-out period, without any medicine. FSH, LH and prolactin serum levels were measured in each one of the subjects by radioimmunoassay before the beginning of each treatment and for at least 14 times during 31 days thereafter. A temporary decrease of the FSH levels and a temporary increase of the prolactin levels were induced by both treatments. In this respect the estradiol enantate effect was more precocious but the quality and the magnitude of the responses were similar among the two substances. The LH profile evolution was different: there was a decrease under estradiol enantate, but a very sharp increasing peak was observed on the 17th day under ethinylestradiol. By comparing the obtained results no significant statistical differences between the estrogenic potencies of the therapeutic schemes applied were found. PMID- 3101712 TI - Abnormalities of lymphocyte subsets and anti-LAV/HTLV-III status in Greek hemophiliacs. AB - Peripheral blood lymphocyte subsets and the incidence of LAV/HTLV-III antibodies were studied in 63 patients with hemophilia A who had been transfused with a low dose regimen of commercial (U.S.A.) factor VIII concentrates. Five patients with hemophilia B were also included in this study. In hemophilia A patients a significant reduction in the percentage and absolute numbers of T4+ cells and of the T4/T8 ratio and a significant increase in the percentage of T8+ and Leu-7+ cells were observed. These abnormalities were independent of the presence of anti LAV/HTLV-III. In hemophilia B patients a significant increase of T8+ cells and a decrease of T4/T8 ratio was noted while the percentage of Leu-7+ cells was normal. A significant negative correlation of F VIII units transfused and T4/T8 ratio was seen only in LAV/HTLV (-) patients, suggesting that F VIII per se could cause immunodysregulation. Seropositive patients were found to have consumed a larger amount of F VIII units than seronegative patients during the period 1980 1984 (p less than 0.005). PMID- 3101713 TI - Mycobacteria and cryptococci cultured from the buffy coat of AIDS patients prior to symptomatology: a rationale for early therapy. AB - Culture of the buffy coat layer of the peripheral blood of 14 AIDS patients demonstrated sustained mycobacteremia or fungemia: 11 with Mycobacterium avium intracellulare, 2 with Cryptococcus neoformans, and one with Mycobacterium tuberculosis. The early detection of these agents prior to the onset of overt symptomatology of disseminated infection due to these microorganisms allowed speculations on an early phase bacteremia and the proposal of prompt inception of antimicrobial therapy while the microbial burden is still manageable. The method also obviates the need for more invasive techniques. PMID- 3101714 TI - [Immunopathologic study of the persistent lymphadenopathies related to LAV-HTLV III infection]. AB - The authors describe the immunopathological findings in the different histopathological types. In type IA, the most important findings are disruption of the network of the intrafollicular dendritic cells, progressive atrophy of the mantle zone as shown with anti-delta antibody, the progressive diminution of the number of CD4 cells first in the germinative centres then in the extrafollicular areas, the progressive increase of CD8 cells first in the germinative centres, the presence of a severe B cells hyperplasia which is polytypic. In type II, the most important findings are the global decrease of T cells predominantly of CD4 cells. These alterations of the repartition of B and T cells is highly suggestive in type IA for LAV infection. These findings have some interest for the understanding of the physiopathology of the disease. PMID- 3101716 TI - Penicillin anaphylaxis. PMID- 3101715 TI - Diabetic ketoacidosis and infection: leukocyte count and differential as early predictors of serious infection. AB - The records of 153 patients who presented to an emergency department with diabetic ketoacidosis were reviewed to determine whether any admission evaluation laboratory data could serve as a predictor of occult or coexisting infection. Ten patients with admission radiographs already demonstrating active infection (pneumonia or tuberculosis) and two patients with wet gangrene of an extremity were not included in subsequent statistical analysis, as their infections were diagnosed on initial evaluation. Analysis of readily available admission variables revealed that when age, sex, temperature, glucose, serum bicarbonate, pH, total leukocyte count, and differential are subjected to univariate and multivariate discriminant analysis, only an elevation in band neutrophils reliably predicted infection. Approximately half of our patients with elevated band counts (10 or greater) had a coexisting occult infection. An elevated band count was predictive of an occult coexisting major infection with a sensitivity of 100% (19/19) and a specificity of 80% (98/122). PMID- 3101717 TI - Stress, pain, and catecholamines in labor: Part 1. A review. PMID- 3101718 TI - [Opportune treatment of hemorrhage in classical hemophilia. Study of the Hemophilia Cooperative Group]. PMID- 3101719 TI - Temporal neocortical injuries in rats impair attending but not complex visual processing. AB - The effects of variations of the distance between the relevant stimuli and the animals' response sites were observed upon the performances of a black-white discrimination habit for normal rats or subjects prepared with either bilateral injuries to the visual or temporal neocortex. In addition, the animals were given a strict test of visual form perception. Subjects with injuries to the visual cortex failed the test of visual form perception but performed like normals in discriminating a spatially discontiguous problem. In contrast, subjects with temporal injuries exhibited enormous performance deficits when trained on a spatially discontiguous problem but performed like normals on the test of form perception. The findings parallel the results of studies using primates and suggest that bitemporal injuries result in impairments of attending and not of complex visual processing. PMID- 3101720 TI - Design of a new automatic chromatography system for efficient enzyme purification equipped with a time-shared multiple activity analyzer. AB - A new system equipped with a computer-controlled multiple activity analyzer has been developed for the efficient purification of multiple enzymes. The system consists of the following units: conventional enzyme fractionation system with a peristaltic pump, liquid chromatographic column, fraction collector, and uv monitor; computer-operated uv-vis spectrophotometer equipped with a thermo regulated metal block and a flow-through type silica cuvette; personal computer; dot matrix printer; cooling facility; and automatic sampling-mixing system. The whole system is operated by a newly designed time-sharing computer program for periodic and repetitive sampling of the column eluants containing multiple kinds of enzymes and of designated assay mixtures for each enzyme and for measurement of the initial velocity of spectrophotometric signals. For example, a mixture of aspartase (EC 4.3.1.1) and malate dehydrogenase (EC 1.1.1.39) and also a mixture of these two enzymes and glutamate dehydrogenase (EC 1.4.1.3 or EC 1.4.1.4) were analyzed by the above system using gel permeation chromatography, and the two or three enzyme activities were repeatedly monitored within 4 min. Based on the above results further possibilities for the application of the system for a variety of purposes are discussed. PMID- 3101721 TI - Characterization of hydantoinase from Pseudomonas fluorescens strain DSM 84. AB - The hydantoinase (EC 3.5.2.2) from Pseudomonas fluorescens strain DSM 84 was purified either by hydrophobic interaction chromatography on phenyl-Sepharose or by salting out chromatography on Sepharose 4B, gel filtration on Sephacryl S-400, and preparative electrophoresis. Molecular weight values of 230,000 and 60,000 for the native enzyme and each of the four subunits were estimated for the hydantoin hydrolysing activity. The hydantoinase was stable at temperatures up to 40 degrees C but showed an optimal activity at 55 degrees C. The enzyme was markedly inhibited by copper, para-hydroxymercuribenzoate, 8-hydroxyquinoline, and 2,2'-dipyridyl but not by zinc, and poorly by EDTA and o-phenanthroline. The hydantoin-hydrolyzing activity could be reactivated by ferrous ions. Dihydrouracil was the most readily hydrolyzed substrate. The dihydropyrimidinase produced by strain DSM 84 could also hydrolyze 5-substituted hydantions such as isopropylhydantoin (valine derivative) continuously for 10 days in a membrane reactor at a conversion rate of 30%. The only identified end product was N carbamyl-D-valine. PMID- 3101722 TI - [Pathophysiological mechanism of pain]. PMID- 3101723 TI - [A study of cerebrovascular autoregulation and CO2 reactivity in putaminal hemorrhage]. AB - Regional cerebral blood flow (rCBF) during hypertension and hypercapnia was studied in 33 patients with putaminal hemorrhage, using a single photon emission CT by means of Xenon 133 inhalation method. The results obtained were as follows: 1) A significant relationship was obtained between the impairment of autoregulation, CO2 reactivity and the degree of cerebral ischemia, i. e., in most cases, these vascular responses were impaired in cases of ischemia showing the rCBF decrease over 30 to 40% of normal values. However, there were particular cases with cerebral ischemia of over 30 to 40% in which autoregulation seemed to be preserved in the acute stage, which was considered to be the similar phenomenon as so called "false autoregulation". 2) The cerebrovascular responses such as autoregulation and CO2 reactivity were preserved in cases of less than 50 ml of hematoma volume. In cases with 50 to 74 ml of hematoma volume however, autoregulation and CO2 reactivity were mostly impaired, especially in the affected hemisphere rather than the non-affected, in the period of 1 to 2 months from the onset. Furthermore, the impairment was also involved in both hemispheres if the hematoma was over 75 ml in volume. 3) The cerebrovascular responses were markedly impaired in the region of basal ganglia of the affected hemisphere which corresponded well to the hematoma site. 4) There was a close correlation between the cerebrovascular responses and the activity of daily life (ADL), i. e, the prognosis might be poor in cases with global impairment, but which seemed to be rather good in cases with local impairment. It might be concluded, from the results mentioned above, that the study of autoregulation and CO2 reactivity is probably significant in estimating the pathogenesis and the treatment of cerebral ischemia following hypertensive putaminal hemorrhage. PMID- 3101724 TI - The response of paediatric arrhythmias to intravenous and oral flecainide. AB - Flecainide acetate was administered intravenously and orally to 12 consecutive children, aged 1-15 years, presenting with arrhythmias that were life threatening or resistant to conventional medical treatment. Three children had arrhythmias related to Wolff-Parkinson-White syndrome, four had concealed accessory pathways, two had His bundle tachycardia, and three had ventricular tachycardia. Of seven patients who were given flecainide intravenously, four returned to sinus rhythm and in a fifth successful rate control of His bundle tachycardia was achieved. All 12 patients were given the drug orally: in nine it was successful in preventing recurrence of arrhythmia, in one satisfactory rate control was achieved, and in two it was withdrawn because it produced more frequent attacks of tachycardia. No other adverse effects occurred. The efficacy and low toxicity of treatment in this study suggests that flecainide acetate may have an important role in the management of selected paediatric arrhythmias. PMID- 3101725 TI - The effects of moderate sustained exercise on the pharmacokinetics of nitroglycerine. PMID- 3101726 TI - Nizatidine (300 mg nocte) does not interfere with diazepam pharmacokinetics in man. PMID- 3101728 TI - Cytochemical investigation of glucose-6-phosphate dehydrogenase activity in rat mammary tissue. AB - Glucose-6-phosphate dehydrogenase (G6PD) activity in epithelial cells from six normal, eight lactating and 21 DMBA tumour bearing rat mammary tissues was investigated using techniques of quantitative cytochemistry. G6PD promoted H+ production was quantified under atmospheres of N2 and O2 in frozen sections from rat mammary tissue in the presence and absence of a H+ acceptor (Total H+ and Type I H+). There was a considerable overlap between the three tissue types in values for Total H+ measured under N2 or O2. However, maximum H+ production in lactating and DMBA tumour tissue took longer to achieve in O2 than in N2 (16-20 min vs 6-8 min). In normal tissue maximum production of Total H+ was not achieved until 45-50 min and the rate of reaction was similar in N2 and in O2. Type I H+ measured in N2 did not vary significantly between DMBA tumours and lactating tissue but under O2 was only present in DMBA tumour, being undetectable in both normal and lactating tissue. The results demonstrate that despite the overlap in G6PD activities between the tissues tested, the techniques of quantitative cytochemistry can provide a functional assay differentiating between non malignant and malignant breast tissue in the rat. PMID- 3101729 TI - The effect of anticoagulant on platelet associated IgG. AB - Blood anticoagulated with solid K2EDTA had platelet associated IgG (PAIgG) levels five-fold greater than citrated blood when the platelets were harvested by differential centrifugation but identical PAIgG levels when the platelets were harvested by Percoll density gradient. Furthermore, blood anticoagulated with increasing amounts of solid K2EDTA demonstrated a proportionate increase in both PAIgG and haemolysis whereas the same blood sample anticoagulated with aqueous K2EDTA exhibited neither of these effects. Coulter Counter analysis of platelet poor plasma (PPP) prepared from blood anticoagulated with solid K2EDTA revealed particles with a mean volume greater than normal RBC; such particles were not found in the PPP prepared from citrated blood. While some of these particles could be sedimented through plasma, those remaining were sufficiently buoyant to resist sedimentation unless the plasma was diluted with buffer. Studies with FITC conjugated antisera revealed that the particles could be classified into two types. Type I particles reacted strongly with a monoclonal anti-RBC antibody, weakly with anti-IgG antibody and had the appearance of stroma. Type II particles lacked any apparent biological structure, reacted strongly with anti-IgG antibody but not with monoclonal anti-RBC antibody. Thus, the buoyant IgG-rich particles found in blood anticoagulated with solid K2EDTA appear to contribute to the high PAIgG levels associated with this anticoagulant. Consequently, solid K2EDTA should not be used to anticoagulate blood destined for PAIgG measurement. PMID- 3101727 TI - Effects of altering surface glycoprotein composition on metastatic colonisation potential of murine mammary tumour cells. AB - This study has examined cells from naturally-occurring murine mammary tumours to ascertain whether cell surface glycoproteins play a significant role in colonisation of the lungs after intravenous inoculation. It was found that gel electrophoretic analysis of membrane extracts and lectin adsorption studies did not reveal any consistent differences in glycoprotein composition of cells from tumours which can heavily colonise the lungs relative to ones from tumours which cannot do so or to cells from pulmonary metastases. Also, alteration of structural and functional properties of surface glycoproteins by treatment with succinylated lectins or with drugs such as tunicamycin and swainsonine, which inhibit glycosylation of membrane proteins, had no specific effects on metastatic colonisation of the lungs. Tunicamycin apparently decreased capability to form experimental metastases but also diminished tumourigenicity on subcutaneous inoculation, although it did not affect tumour cell viability in vitro. This information supports earlier studies from this laboratory involving enzymic digestion of the surface of living tumour cells before inoculation and demonstrates that the pulmonary colonisation capability of these mammary tumour cells can withstand global disorganisation of membrane glycoprotein structure and composition. This implies that either the surface glycoproteins are not important in the colonisation process, or that these tumour cells have great capability for rapid repair of their surfaces. It is concluded that a clear answer to whether surface glycoprotein composition has a decisive role in pulmonary colonisation by these mammary tumour cells requires introduction of stable heritable traits into tumour cell populations by genetic manipulation. PMID- 3101730 TI - Lupus-type coagulation inhibitor in hairy cell leukaemia and resolution with splenectomy. PMID- 3101731 TI - A preparation for calibrating the assay of the blood group antibody anti-c. AB - A freeze-dried, working calibration preparation (84/628) has been assayed against the International Incomplete anti-c Reference Serum (67/160) in a multi-centre study. The use of 84/628 will avoid the between-laboratory variation, inherent in the use of local preparations, in the reporting of assays of anti-c using the AutoAnalyzer. A value of 13 IU/ampoule has been assigned to the anti-c content of preparation 84/628 which is available from the Blood Group Reference Laboratory, Oxford. PMID- 3101732 TI - Demonstration of abnormal factor VIII multimers in acquired von Willebrand's disease associated with a circulating inhibitor. AB - We have studied the factor VIII multimeric structure in four patients with acquired von Willebrand's disease associated with a circulating inhibitor to the factor VIII complex. In three of the four patients tested, the high and medium molecular weights bands were absent when assessed by sodium dodecyl sulphate agarose electrophoresis. Plasma from the fourth patient contained all the factor VIII multimeric forms, although the high molecular weight bands were markedly decreased in concentration. Intravenous infusion of 1-deamino-(8-D-arginine) vasopressin (DDAVP) resulted in the appearance of a full complement of multimers in the plasma of the two patients tested. This response was, however, transient and a return to pre-infusion multimeric composition occurred within 2-4 h. In the patients studied, an inhibitor to the factor VIII complex has induced an acquired variant von Willebrand's disease which transiently corrects after the infusion of DDAVP. PMID- 3101733 TI - Energy expenditure of agricultural workers in an area of endemic schistosomiasis in the Sudan. AB - Indices of physiological performance in the field under natural working conditions were measured in 46 Sudanese Gezira villagers and related to exercise performance under controlled laboratory conditions. The effect of Schistosoma mansoni infection on energy expenditure in the field was also investigated. A highly significant positive association between the maximal aerobic power output (VO2 max) measured in the laboratory with energy expenditure in the field (r = + 0.51, p less than 0.001) and with changes in body weight during work (r = 0.41, p less than 0.01) was found. The villagers' energy expenditure in field work amounted to 25-28 KJ/min, which corresponded to more than 50% of their predicted VO2 max. They maintained that relative work level for more than an hour. The differences in energy expenditure between moderately infected and non-infected villagers with schistosomiasis did not attain statistical significance but the number of non-infected subjects on which the comparison was based was small. PMID- 3101734 TI - Nutritional management of pregnancy in patients on home parenteral nutrition. AB - Three pregnancies are reported in two patients on home parenteral nutrition for intestinal failure. The nutritional regimen, 2300 kcal (9.63 MJ) (18% as lipid emulsion), 14 g amino acid nitrogen and electrolytes supplied daily in a 'big bag', was based on the measured resting energy expenditure and urinary nitrogen excretion during the third trimester in a 30-year-old woman on home parenteral nutrition. Commercial preparations of trace elements were added to the infusion as dictated by serum levels. Iron, iodine and fluoride were given orally, and vitamin B12 by monthly intramuscular injection. There were no serious deficiencies in trace elements and maternal weight-gain and fetal growth were satisfactory in all three pregnancies. The two pregnancies in one patient went to term and both infants had birthweights at the 50th centile for gestational age. The second patient who had had two spontaneous abortions went into premature labour at 30 weeks and gave birth to a baby with a minor facial deformity who subsequently developed the idiopathic respiratory distress syndrome. All three placentas were histologically normal. The growth and development of all three babies has been satisfactory. This nutritional regimen should be adequate for most pregnant patients who have attained a normal nutritional status on parenteral nutrition. PMID- 3101735 TI - Dihydrolipoyl transacetylase of Escherichia coli. Formation of 8-S acetyldihydrolipoamide. AB - The dihydrolipoyl transacetylase component (E2) of the pyruvate dehydrogenase complex catalyzes the reaction of acetyl coenzyme A (acetyl-CoA) with dihydrolipoamide, producing coenzyme A and S-acetyldihydrolipoamide. The acetyl group is shown by experiments reported herein to be bonded to S8 in the enzymatic product. 1H NMR analysis of synthetic samples of both structural isomers of S acetyl-S-(phenylmercurio)dihydrolipoamide enabled structural assignments to be made. Reaction of 8-S-acetyl-6-S-(phenylmercurio)dihydrolipoamide with 3 mercaptopropionic acid in chloroform produced 8-S-acetyldihydrolipoamide which contained a small amount (5%) of the 6-S isomer. Reaction of 6,8-di-S acetyldihydrolipoamide with NH2OH produced a 4:1 mixture of 6-S acetyldihydrolipoamide and the 8-S isomer. These compounds did not isomerize at significant rates in chloroform but rapidly isomerized to the equilibrium mixture in aqueous solution (Keq = 3.4). The second-order rate constants for the hydroxide-catalyzed isomerization were found to be kf = (1.15 +/- 0.07) X 10(6) M 1 X s-1 and kr = (3.36 +/- 0.20) X 10(5) M-1 X s-1 in the direction of the formation of the 8-S isomer. The enzymatic product was trapped by addition of phenylmercuric hydroxide within 15 s-30 min after starting the reaction. 1H NMR analysis of the products obtained at various times showed that the enzymatic product was 8-S-acetyldihydrolipoamide, which underwent progressive isomerization to the mixture of isomers within a few minutes. In the reaction of acetyl-CoA with dihydrolipoamide, the latter substrate reacts in place of enzyme-bound dihydrolipoyl moieties. Therefore, acetylation occurs at the 8-S position of bound lipoyl groups. PMID- 3101736 TI - Fluorescent labeling of bacteriorhodopsin: implications for helix connections. AB - Purple membrane from Halobacterium halobium was reacted with dansyl (5 dimethylamino-1-naphthalenyl fluorescent labels that have specificity for different protein side chains of bacteriorhodopsin. Dansyl chloride was found to react primarily with Lys-41. Dansyl hydrazine was coupled, with water-soluble carbodiimide, to Glu-74 and/or Asp-85, which was the major modified site after papain-cleavage of the carboxyl-terminal 17 amino acids. Fluorescence energy transfer was used to probe the proximity of the modified sites to the retinal chromophore of bacteriorhodopsin. The dansyl group on Lys-41 was greater than 2.99 nm from retinal, while the dansyl group on Glu-74/Asp-85 was greater than 2.10 nm from retinal. Information available on the location of retinal in the transmembrane profile and probable surface locations of the fluorescent labels was combined with the energy transfer results to calculate distances projected in the plane of the membrane. The projected distances to retinal were 1.64 nm (Lys 41) and 1.65 nm (Gly-74). These measurements, combined with many other labeling experiments that have been reported, restrict the number of likely helix connection models to only three: EDCABGF, FEDCBAG and FGEABDC (in the nomenclature of Engelman et al. (1980) Proc. Natl. Acad. Sci. USA 77, 2023-2027). PMID- 3101737 TI - Organization of genes for ribosomal proteins S7 and S12, elongation factors EF-Tu and EF-G in the cyanobacterium Spirulina platensis. AB - The gene encoding ribosomal proteins S12 and probably S7 as well as protein synthesis elongation factors Tu (EF-Tu) and G (EF-G) of Spirulina platensis have been identified and cloned. Gene expression was determined for ribosomal protein S12 by genetic complementation of the appropriate Escherichia coli mutant, whereas for the EF-Tu gene it was determined by production of the protein in E. coli minicells. On the basis of these experiments we suggest the following gene order in the S. platensis chromosome: S12, S7, EF-G, EF-Tu. PMID- 3101738 TI - DNA- and RNA-binding proteins of chromatin from Escherichia coli. AB - The different proteins present in chromatin of Escherichia coli have been analyzed by a variety of techniques. The chromatin was isolated using a previously published procedure (Sjastad, K., Fadnes, P., Kruger, P.G. Lossius, I. and Kleppe, K. (1982) J. Gen. Microbiol. 128, 3037) and solubilized by the action of micrococcal nuclease or DNAase I. The DNA-protein and RNA-protein complexes thus obtained were purified by sucrose gradient centrifugation and isopycnic gradient centrifugation in metrizamide in low ionic strength. The protein: DNA ratio of the DNA-protein complexes was estimated from the latter method and found to be approx. 1.75. The protein components were analyzed further by one- and two dimensional gel electrophoresis. Approx. 15 major polypeptides were detected in the DNA-protein complex, whereas 10 were present in the RNA-protein complex. The majority of the polypeptides in both complexes had acidic isoelectric pH. The polypeptides in the two complexes differed markedly and only two polypeptides, having molecular weights of 57,000 and 37,000, respectively, were found to be common in both complexes. In agreement with earlier studies, the basic protein HU was not present in the DNA-protein complex. Affinity studies of the proteins from chromatin using DNA- and RNA-Sepharose columns in general confirmed the above conclusions. The two-dimensional gel electrophoretic patterns of the proteins in the different complexes were compared with those of proteins in the inner and outer membranes. Only one of the major polypeptides present in the inner membrane, having a molecular weight of 57,000, was enriched in the DNA-protein complex. PMID- 3101739 TI - Structural relationships of the major glycoproteins from human alveolar proteinosis surfactant. AB - Alveolar proteinosis is a disease characterized by accumulation of proteinaceous material in the alveolar space of the lung. Two major collagenase-sensitive polypeptides, alveolar proteinosis peptides of 34 kDa kilodaltons (APP-34) and of 62 kDa (APP-62), were isolated from bronchioalveolar lavage of patients with alveolar proteinosis. These proteins co-purified during fast-performance liquid chromatography (FPLC) chromatofocusing and were separated from each other by electroelution following SDS-polyacrylamide gel electrophoresis. Immunoblot analysis of these proteins demonstrated that both shared antigenic sites with the normal human surfactant-associated protein of Mr 34,000 (SAP-34) using both polyclonal and monoclonal antibodies generated against SAP-34. Removal of asparagine-linked oligosaccharides from the 34 kDa and 62 kDa alveolar proteinosis proteins with endoglycosidase F resulted in polypeptides of 28 kDa from APP-34 and 56 kDa from APP-62. Amino acid analysis and tryptic peptide maps of the electroeluted APP-34 and APP-62 proteins were essentially identical and similar to that previously reported for human SAP-34, supporting the likely relationship of APP-34 and APP-62 as monomer and dimer of the normal SAP-34. APP 34 and APP-62 were both sensitive to bacterial collagenase, yielding collagenase resistant fragments of 21 kDa, similar in migration and amino acid composition to the fragment generated by collagenase digestion of normal human SAP-34. High molecular weight aggregates of APP-34 and APP-62 were the result of sulfhydryl dependent and non-sulfhydryl-dependent cross-linking. A domain in the C-terminal non-collagenous portion of the molecules which forms sulfhydryl-dependent oligomers was identified. The two major polypeptides accumulating in the airway of patients with alveolar proteinosis are monomeric (34 kDa) and dimeric (62 kDa) forms of the major surfactant-associated glycoprotein, SAP-34. PMID- 3101740 TI - Characterization of two hemorrhagic zinc proteinases, toxin c and toxin d, from western diamondback rattlesnake (Crotalus atrox) venom. AB - Two hemorrhagic proteinases from Crotalus atrox venom, hemorrhagic toxin c (Ht-c) and hemorrhagic toxin d (Ht-d), were characterized and compared to one another. The two toxins are zinc metalloproteinases which both have molecular weights of 24,000. Their isoelectric points are slightly acidic, Ht-c being the more basic of the two with an isoelectric point of 6.2, whereas Ht-d has an isoelectric point of 6.1. Only minor differences were found in the amino acid compositions of the two toxins. The toxins were both demonstrated to be hemorrhagic, using an in vivo assay, and also proteolytic. Prior treatment of the hemorrhagic proteinases with ethylenediaminetetraacetic acid and o-phenanthroline eliminated both the hemorrhagic and the proteolytic activities. Aprotinin and phenylmethylsulfonyl fluoride had no effect upon these activities. The pH optimum of the proteolysis by Ht-c and Ht-d on hide powder azure as the substrate was between pH 8 and pH 9. The circular dichroism spectra for Ht-c and Ht-d appear almost identical with respect to minima positions and elipticities, indicative of very similar solution structures for the two enzymes. Antiserum raised in mice against Ht-c was assayed on double-diffusion Ouchterlony plates for cross-reactivity with other hemorrhagic toxins from C. atrox venom. From this experiment it was concluded that the two hemorrhagic proteinases Ht-c and Ht-d share identical antigenic structures. This was corroborated by tryptic mapping of the two toxins. Only one major difference was observed from the maps. In the case of Ht-c, it was determined that an aspartate was substituted by an alanine when compared to Ht-d. From these characterization studies we conclude that Ht-c and Ht-d are isoenzymes with only very minor differences in their structures. PMID- 3101741 TI - A kinetic study of the melanization pathway between L-tyrosine and dopachrome. AB - In the pathway of melanin biosynthesis originating from L-tyrosine, the dopachrome accumulation at physiological pH is produced with a pronounced lag period, during which the level of L-dopa increases, following a sigmoidal kinetics to reach a steady-state. A kinetic model has been proposed for the overall pathway of melanization from L-tyrosine to dopachrome; it explains the lag period present during the dopachrome accumulation as well as the influence of L-tyrosine and tyrosinase over this lag period. Use of this model is also valid to explain the kinetics of L-dopa accumulation in the reaction medium, as has been tested by simulation. PMID- 3101742 TI - Comparing binding of histamine and H2-antagonist with their effects on gastric acid secretion. AB - A microsomal fraction from isolated frog gastric mucosa was used to study the binding of labeled histamine, labeled metiamide (a histamine H2-antagonist), and competition between labeled histamine and unlabeled metiamide. The separation of free from bound ligand was done by gel chromatography. The acid secretion was studied in frog gastric mucosa in vitro by a pH-stat method. The binding data could be interpreted in terms of two independent binding sites for both histamine and metiamide. However, the competition between histamine and metiamide does not support the independence of the sites. Moreover, the dissociation kinetics of labeled metiamide in the presence of unlabeled metiamide is non-monotone and, thus, indicates cooperativity. In the physiological studies, the dependence of the rate of acid secretion on histamine stimulation occurs within very narrow limits, which is the result of characteristics other than related to binding. However, the total amount of acid secreted caused by a pulse of histamine does indicate two sites, of which the high-affinity site is the more effective. Metiamide inhibition of acid secretion can be interpreted as an interaction between high-affinity sites of histamine and metiamide. Overall, studies involving physiological effects provide less precise data than the direct binding studies. PMID- 3101743 TI - Prostaglandin E2, prostaglandin E1 and thromboxane B2 release from human monocytes treated with C3b or bacterial lipopolysaccharide. AB - C3b or lipopolysaccharide treatment of human peripheral blood monocytes in culture stimulates an early release of thromboxane B2 and a delayed release of prostaglandin E into culture supernatants. Immunoreactive thromboxane B2 release is maximal from 2-8 h, whereas prostaglandin E release is maximal from 16-24 h after stimulation of monocytes in culture. We further examined this process by comparing the time course of labelled prostaglandin E2, prostaglandin E1 and thromboxane B2 release from human monocytes which were pulse or continuously labelled with [3H]arachidonic acid and [14C]eicosatrienoic acid. The release of labelled eicosanoids was compared with the release of immunoreactive prostaglandin E and thromboxane B2. The time course of prostaglandin E2 release was virtually identical to the release of prostaglandin E1 in all culture supernatants regardless of labelling conditions. However, release of immunoreactive prostaglandin E paralleled the release of labelled prostaglandin E1 and E2 only for continuously labelled cultures. The release of labelled prostaglandin E1 and E2 from pulse labelled cultures paralleled the release of thromboxane B2 and not immunoreactive prostaglandin. In contrast, labelled and immunoreactive thromboxane B2, quantitated in the same culture supernatants, demonstrated similar release patterns regardless of labelling conditions. These findings indicate that the differential pattern of prostaglandin E and thromboxane B2 release from human monocytes is not related to a time-dependent shift in the release of prostaglandin E1 relative to prostaglandin E2. Because thromboxane B2 and prostaglandin E2 are produced through cyclooxygenase mediated conversion of arachidonic acid, these results further suggest that prostaglandin E2 and thromboxane B2 are independently metabolized in human monocyte populations. PMID- 3101744 TI - Differences between glycogen synthases from rat and rabbit skeletal muscle as indicated by phosphopeptide maps. AB - Glycogen synthase I was purified from rat skeletal muscle. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the enzyme migrated as a major band with a subunit Mr of 85,000. The specific activity (24 units/mg protein), activity ratio (the activity in the absence of glucose-6-P divided by the activity in the presence of glucose-6-P X 100) (92 +/- 2) and phosphate content (0.6 mol/mol subunit) were similar to the enzyme from rabbit skeletal muscle. Phosphorylation and inactivation of rat muscle glycogen synthase by casein kinase I, casein kinase II (glycogen synthase kinase 5), glycogen synthase kinase 3 (kinase FA), glycogen synthase kinase 4, phosphorylase b kinase, and the catalytic subunit of cAMP-dependent protein kinase were similar to those reported for rabbit muscle synthase. The greatest decrease in rat muscle glycogen synthase activity was seen after phosphorylation of the synthase by casein kinase I. Phosphopeptide maps of glycogen synthase were obtained by digesting the different 32P-labeled forms of glycogen synthase by CNBr, trypsin, or chymotrypsin. The CNBr peptides were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and the tryptic and chymotryptic peptides were separated by reversed-phase HPLC. Although the rat and rabbit forms of synthase gave similar peptide maps, there were significant differences between the phosphopeptides derived from the N-terminal region of rabbit glycogen synthase and the corresponding peptides presumably derived from the N-terminal region of rat glycogen synthase. For CNBr peptides, the apparent Mr was 12,500 for rat and 12,000 for the rabbit. The tryptic peptides obtained from the two species had different retention times. A single chymotryptic peptide was produced from rat skeletal muscle glycogen synthase after phosphorylation by phosphorylase kinase whereas two peptides were obtained with the rabbit enzyme. These results indicate that the N-terminus of rabbit glycogen synthase, which contains four phosphorylatable residues (Kuret et al. (1985) Eur. J. Biochem. 151, 39-48), is different from the N-terminus of rat glycogen synthase. PMID- 3101745 TI - Recovery of porcine aortic endothelial cell prostaglandin synthesis following inhibition by sublethal concentrations of hydrogen peroxide. AB - Confluent monolayers of porcine aortic endothelial cells exposed for 10 min to 100 microM H2O2 lose their capacity to produce prostaglandins in response to addition of saturating exogenous arachidonic acid. Significant recovery of prostaglandin I2 and E2 synthesis occurred within 3 h and full enzymatic capacity returned by 6 h. Reducing the injury by exposure to half the amount of H2O2 allowed prostaglandin I2 production to recover to a greater extent in 3 h, while cells exposed for 60 min to either 0.5 or 1.0 mM H2O2 demonstrated no recovery. Pre-treatment with either actinomycin D or cycloheximide also prevented recovery following exposure to 100 microM peroxide. Injured cells did not recover when incubated with balanced salts after removal of peroxide, while incubation with medium 199 allowed for the complete return of synthetic capacity. Addition of 1% fetal calf serum in medium 199 did not facilitate recovery. Production of prostaglandins from endogenous arachidonic acid, released by either bradykinin or the ionophore A23187, was also inhibited by H2O2 exposure, however, full recovery of this stimulated synthesis occurred within 3 h. Cycloheximide pre-treatment completely inhibited recovery of bradykinin-induced prostaglandin I2 synthesis. These data demonstrate that sublethal concentrations of H2O2 irreversibly inactivate fatty acid cyclooxygenase and that synthesis of new enzyme is required for recovery. This return of activity occurs more rapidly for production of prostaglandins from endogenous arachidonic acid compared with production following addition of exogenous substrate. PMID- 3101746 TI - Effect of phorbol 12-myristate 13-acetate (PMA) on agonist-induced arachidonate release and 5-hydroxytryptamine secretion in human platelets. Dependence of effects on agonist type and time of incubation with PMA. AB - We have previously demonstrated synergistic potentiation of secretion by phorbol 12-myristate 13-acetate (PMA) and platelet agonists such as thrombin and the thromboxane mimetic, U46619, with short (less than 2 min) pre-incubations of PMA, despite inhibition of agonist-induced [Ca2+]i mobilization and arachidonate/thromboxane release. In this study, the effect of PMA on 5 hydroxytryptamine secretion in relation to arachidonate/thromboxane B2 release induced by collagen as well as the 'weak agonists', ADP, adrenaline and platelet activating factor (PAF), was investigated using human platelet-rich plasma. Short incubations (10-30 s) with PMA (400 nM) before agonist addition caused an inhibition (60-100%) of 5-hydroxy[14C]tryptamine secretion and thromboxane B2 formation in response to maximally effective doses of ADP (10 microM), adrenaline (10 microM) and PAF (0.5 microM) but potentiated collagen-induced 5 hydroxy[14C]tryptamine secretion and [3H]arachidonate/thromboxane release. However, a longer pre-incubation with PMA (5 min) caused a significant reduction (20-50%) in the extent of collagen-induced 5-hydroxy[14C]tryptamine secretion and thromboxane B2 formation as seen earlier with thrombin, although collagen-induced [3]arachidonate release was still unaffected. Pretreatment of platelets with the cyclo-oxygenase inhibitor, indomethacin (10 microM), abolished 5 hydroxy[14C]tryptamine secretion in response to the weak agonists and reduced collagen (2.5-10 micrograms/ml) -induced secretion by 50-90%, depending on the collagen concentration. Addition of PMA (400 nM) 10 s before these agonists in indomethacin-treated platelets resulted in synergistic interactions between agonist and PMA leading to enhanced 5-hydroxy[14C]tryptamine secretion, although this was notably less than the synergism observed previously between thrombin and PMA or U46619 and PMA. The results suggest that the effect of short incubations with PMA on 5-hydroxytryptamine secretion induced by 'thromboxane-dependent' agonists, such as those examined in this study, is determined by the effect on agonist-induced thromboxane synthesis. However, when endogenous thromboxane synthesis is blocked, weak agonists as well as collagen can synergize with PMA at potentiating 5-hydroxytryptamine secretion, albeit to a weaker extent than thrombin or U46619. The results also suggest that PMA has differential effects on arachidonate release induced by collagen and thrombin. PMID- 3101747 TI - Comparisons of large subunit rRNAs reveal some eukaryote-specific elements of secondary structure. AB - All large rRNAs possess a common core of secondary structure. However, large variations in the size of the molecule have arisen during evolution, which are accommodated over a dozen rapidly evolving domains. Most of the enlargement of the eukaryotic molecules (as compared to prokaryotes) is in fact restricted over only two of these divergent domains, which are dramatically expanded in vertebrates. We have derived secondary structure models for these two domains through a systematic comparison of all the pro- and eukaryotic sequences published so far. Within each of these domains, a subset of secondary structure elements which are specific to eukaryotes is detected. Archaebacterial-specific secondary structures can also be identified which appear to be maintained through a strong selective constraint. The relative preservation of such group-specific structures raises the issue of their potential involvement in some diversification of ribosomal functions among the three fundamental phylogenetic groups, eubacteria, archaebacteria and eukaryotes. We also show that eukaryotic ribosomal RNAs are subjected, over their entire length, to a unique type of compositional constraint which may largely differ among the major eukaryotic taxa. PMID- 3101748 TI - Horseradish peroxidase: a useful tool for modeling the extra-hepatic biooxidation of exogens. PMID- 3101749 TI - Glutathione status of rat thymocytes and splenocytes during the early events of their ConA proliferative responses. AB - Glutathione plays an important role in the lymphocyte mitogenic response. We have demonstrated that 2-ME increases the ConA proliferative response of rat splenocytes and in parallel, causes an enhancement of glutathione synthesis in these cells. On the other hand, 2-ME had the same action on the glutathione level of thymocytes during the late phase of their mitogenic response, but it had no effect on the [3H]thymidine uptake of these cells. To clarify this discrepancy and the role of glutathione during the mitogenic response, we studied the glutathione status of thymus cells during the early phase of the ConA-induced proliferative response in the presence or the absence of 2-ME in parallel with that of whole spleen cells and the T cell fraction of splenocytes. During the early events of the mitogenic response, i.e., during the 24th h, we observed a normal 2 GSSG/GSH + 2 GSSG ratio in cultured cells, indicating a normal redox state, and that ConA involved an increased glutathione level in thymocytes but not in whole splenocytes and in splenic T cells. 2-ME had no effect on the glutathione level of stimulated thymocytes during the early phase of the mitogenic response. This phenomenon could be related to an absence of its effect on [3H]thymidine uptake. On the other hand, 2-ME induced an enhancement of the glutathione level and [3H]thymidine uptake in the two types of stimulated splenocytes. This study suggest that thymocytes do not have the same mechanism of glutathione synthesis induction as that which occurs in splenocytes during the ConA proliferative response. This mechanism could be related to the maturation state of the T cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101750 TI - The relationship between HDL-, LDL-, liposomes-free cholesterol, biliary cholesterol and bile salts in the rat. AB - In order to study the relationship between bile cholesterol and free cholesterol carried by high and low density lipoproteins (HDL and LDL), 10 male Wistar rats, 11 weeks old and fed with a standard diet were divided into 3 groups which received an intravenous infusion (jugular vein) of either LDL, HDL or liposomes. Liposomes were used for comparison because they are assimilated by hepatocytes, but are not recognized by specific receptors. HDL isolated from rat sera were labeled with [14C]cholesterol by molecular exchange and LDL were labeled by exchange with [14C]cholesterol incorporated into phosphatidyl choline/cholesterol liposomes. The peaks of radioactivity appeared in bile 30 min after the HDL or liposome injection and after 210 min for the LDL injection. The kinetic behavior of the cholesterol carried by the liposomes was quite similar to that of cholesterol carried by HDL. Cholesterol carried by HDL was metabolized in bile salts faster than that carried by LDL: cholesterol-HDL or cholesterol-liposomes contributed to the same extent to the secretion of bile cholesterol (15 and 11%, respectively, of the injected dose), LDL (20% of the injected dose). However, the main part of [14C]cholesterol from HDL, LDL or liposomes was metabolized in bile salts. Thus, cholesterol from an exogenous source seemed to be used mainly as a substrate for bile salts. Our study revealed a difference between the hepatic metabolism of HDL, liposomes and LDL in the rat: the kinetic difference between the secretions of the radioactive compounds in bile may be explained by differences in assimilation, intracellular pathways or bile secretion. PMID- 3101751 TI - Solubilization, purification and characterization of D-alanine dehydrogenase from Pseudomonas aeruginosa and effects of solubilization on its properties. AB - D-alanine dehydrogenase, an inducible, membrane associated enzyme of Pseudomonas aeruginosa was solubilized from envelope preparations by treatment with Triton X 100 and purified 31-fold in the presence of 0.05% Triton X-100 to 60% homogeneity. Gel electrophoresis indicated the presence of a single subunit of approximately 49,000 molecular weight. The enzyme contained FAD, and absorption spectra were typical of an iron-sulfur flavoprotein. Solubilization produced significant changes in some properties of the enzyme: solubilized enzyme showed increased affinity for D-alanine; a broader substrate specificity; and increased temperature sensitivity, compared with the membrane associated form. PMID- 3101752 TI - Soluble form of acetylcholinesterase from rabbit enterocytes: comparison of its molecular properties with those of the plasma membrane species. AB - A soluble form of acetylcholinesterase was shown to be present in rabbit enterocytes. The enzyme was obtained from a high-speed supernatant (105,000 X g centrifugation) after homogenization of intestinal mucosa without detergent. It was shown to possess no obvious hydrophobic character and could be classified as a low-salt-soluble (LSS) acetylcholinesterase. Sucrose gradient centrifugation revealed a single enzyme species with a sedimentation coefficient of 3.9 +/- 0.2S. By gel filtration performed in HPLC the enzyme was eluted as a protein corresponding to an Mr of 72,000 +/- 3,000. It could be precipitated with concanavalin A by affinoelectrophoresis, but the catalytic activity was not affected by the lectin. Our results are consistent with a G1 globular form for this soluble acetylcholinesterase which differs very clearly from detergent soluble forms also found recently in the plasma membranes of rabbit enterocytes. PMID- 3101754 TI - [Autoregulation of alpha-amylase formation in Bacillus subtilis]. AB - The phenomenon of self-regulation of alpha-amylase formation in Bacillus subtilis is discovered. The dependence of regulatory effect upon the phase of culture development in shown. PMID- 3101753 TI - [The yield of visible mutations, spontaneous and N-nitroso-N-ethylurea-induced, in the Drosophila mei-9 11 strain defective for excision repair]. AB - The increase of spontaneous and induced frequencies in mature sperm by N-nitroso N-ethylurea visible mutation in the stock mei-9(11) of Drosophila melanogaster blocking the excision reparation has been shown. It is suggested that the mutation mei-9(11) blocks the correct way of reparation that is shown in mutator effect of this mutation. PMID- 3101755 TI - Thyrotropin, prolactin, and growth hormone responses to thyrotropin-releasing hormone in anorexia nervosa and bulimia. AB - Serum thyrotropin (TSH), prolactin (PRL), and growth hormone (GH) levels were measured before and after stimulation with thyrotropin-releasing hormone (TRH) in 10 patients with bulimia, 7 with features of the restricting subtype of anorexia nervosa, and 6 with bulimic subtype of anorexia nervosa. The mean basal levels of TSH, PRL, and GH did not differ among the three groups. A delayed TSH response was found in 86% of the restricting anorectics, 80% of the bulimic anorectics, and 22% of the bulimics. The PRL response was normal in all patients, with no significant difference among the three groups. Elevated basal GH levels were found in 29% of the restricting anorectics, 33% of the bulimic anorectics, and 33% of the bulimics. An abnormal GH increase after TRH stimulation was observed in 50% of the restricting anorectics, 20% of the bulimic anorectics, and 13% of the bulimics. These results suggest that some patients with bulimia, and some with anorexia nervosa, have a hypothalamic dysfunction. These neuroendocrine abnormalities do not appear to be due solely to low weight or to metabolic changes resulting from binge eating and are not associated with depressive symptoms. PMID- 3101756 TI - TRH test, DST, and response to desipramine in primary degenerative dementia. AB - The relationship of primary degenerative dementia (PDD) to major depressive disorder (MDD) is important clinically and theoretically. Neuroendocrine challenge strategies in PDD have focused primarily on the hypothalamic-pituitary adrenal axis, have had varied results, and have not been coupled with assessment of response to antidepressant therapy. We studied the Thyrotropin-Releasing Hormone (TRH) test, the Dexamethasone Suppression Test (DST), and response to desipramine in 12 patients with PDD and 10 patients with MDD. The PDD patients had a high percentage of abnormal TRH tests and DSTs. This was not associated with improvement on desipramine. PMID- 3101757 TI - Feedback effects of ovarian steroids on the hypothalamic-hypophyseal axis in the rabbit. AB - The feedback effects of two ovarian steroids, estradiol-17 beta (E2) and 20 alpha hydroxypregn-4-en-3-one (20 alpha OH), were examined in both intact (INT) and ovariectomized (OVEX) does. We measured steroid-induced alterations in endogenous gonadotropin-releasing hormone (GnRH) from sequential 10-min samples of hypothalamic perfusates, simultaneous changes in peripheral plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the modification of pituitary responsiveness, i.e., increments in plasma LH (delta LH) and plasma FSH (delta FSH), after 50 ng, 250 ng, and 1 microgram of exogenous GnRH in individual does of 6 treatment groups. The groups were: INT does, OVEX does, OVEX does receiving either one (1 E2) or two (2 E2) E2-filled Silastic capsules, OVEX does receiving a 20 alpha OH-filled capsule (20 alpha OH), and OVEX does receiving both capsules of E2 and 20 alpha OH (1 E2 + 20 alpha OH). Ovariectomy enhanced the pulsatile release of hypothalamic GnRH and pituitary LH and FSH, and increased the LH response (delta LH) to exogenous GnRH (OVEX vs. INT, p less than 0.05). Replacement of E2 at the time of ovariectomy prevented the increased GnRH and gonadotropin secretion as well as the enhanced delta LH that were observed in untreated OVEX does. The release of hypothalamic GnRH in the 20 alpha OH group was lower (p less than 0.05) than that in the OVEX group and not different from that in the INT group. The release of pituitary LH and FSH and the delta LH in the 20 alpha OH group was not different from that in the OVEX group, but these parameters were greater (p less than 0.05) than those in the INT group. The hypothalamic GnRH pulse frequency in the 1 E2 + 20 alpha OH group was lower (p less than 0.05) than that in either the 1 E2 or the 20 alpha OH group, but the delta LH in the 1 E2 + 20 alpha OH group was not different from that in either the 1 E2 or the 20 alpha OH group. The highest dose (1 microgram) of exogenous GnRH stimulated a modest increase in FSH in the OVEX, 20 alpha OH, 1 E2 + 20 alpha OH, and 1 E2 groups; but a steroid effect on delta FSH among these 4 groups was not apparent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3101758 TI - Photoperiod, follicle-stimulating hormone receptors, and testicular function in vizcacha (Lagostomus maximus maximus). AB - In the present work we investigated the presence of testosterone in serum and follicle-stimulating hormone (FSH) receptors in testes of the vizcacha (Lagostomus maximus maximus), a South American rodent. We also investigated the effect of constant light on both parameters. The control group consisted of vizcachas caught in their natural habitat and maintained under continuous darkness; the experimental group consisted of animals maintained under constant light (1076 lx) for 8 days. The results revealed a significant decrease in serum testosterone and FSH receptors when the animals were maintained under constant light, as compared to the control group. Androstenedione was elevated in the serum obtained from the experimental group. It is postulated that the pineal gland may regulate testosterone secretion through FSH receptors and through an enzymatic blockade in the steroidogenic pathway; this supposition, however, remains to be proved. PMID- 3101759 TI - Inhibition of gonadotropin-stimulated adenylate cyclase by dansyl-arginyl-(4' ethyl)piperidine amide (DAPA). AB - Protease inhibitors are known to suppress basal, fluoride-, and hormone stimulated adenylate cyclase activities. The thrombin inhibitor, dansyl-arginyl (4'-ethyl)piperidine amide (DAPA), also specifically inhibits the binding of gonadotropins to their receptors. Our studies were undertaken to find a concentration of DAPA that would specifically inhibit gonadotropin-stimulated adenylate cyclase without significantly altering basal, fluoride-, isoproterenol , or prostaglandin E1-stimulated cyclase. Basal adenylate cyclase activity was not inhibited by DAPA in either human chorionic gonadotropin (hCG)- or follicle stimulating hormone (FSH)-responsive rat ovarian plasma membranes. Human chorionic gonadotropin-stimulated cyclase was completely inhibited by DAPA at a concentration of 2.96 mM; the ID50 was 1.32 mM. Follicle-stimulating hormone stimulated cyclase was completely inhibited by a DAPA concentration of 4.44 mM, and the ID50 was 1.75 mM. Dansyl-arginyl-(4'-ethyl)piperidine amide (2.96 mM) inhibited isoproterenol-, prostaglandin E1-, and fluoride-stimulated cyclase in hCG-responsive membranes by 11%, 28%, and 35%, respectively. Dansyl-arginyl-(4' ethyl)piperidine amide (4.44 mM) inhibited fluoride- and prostaglandin-stimulated cyclase in FSH-responsive membranes by 10% and 11%, respectively. The data show that appropriate concentrations of DAPA can antagonize gonadotropin-stimulated adenylate cyclase while only minimally affecting fluoride- and other receptor activated cyclase activities. PMID- 3101760 TI - Origin of low-frequency motions in biological macromolecules. A view of recent progress in the quasi-continuity model. AB - The recent progress in the quasi-continuity model and its applications in studying the low-frequency internal motions of biological macromolecules have been surveyed. Emphasis is placed on revealing the origin of this kind of internal collective motion, which involves many atoms and has significant biological functions. In light of such a line, the low-frequency motions in alpha helix structure, beta-structure (including beta-sheet and beta-barrel), and DNA double-helix structure, the three most fundamental component elements in biological macromolecules, are discussed, and the corresponding physical pictures described. It turns out that the low-frequency motion in biological macromolecules originates from their two common intrinsic characteristics, i.e., they possess a series of weak bonds, such as hydrogen bonds and salt bridges, and a substantial mass distributed over the region containing those weak bonds. PMID- 3101761 TI - [Mechanism of the participation of bone marrow cells in coagulation processes]. AB - The experiment on rats has shown that bone marrow coagulolytic properties were higher than those of the circulating blood. It is suggested that one of the mechanisms of bone marrow participation in the regulation of haemostasis is its ability to influence fibronectin and Ag VIII factor blood level. PMID- 3101762 TI - [Comparative biochemical and electron microscopic research on the membrane damaging action of a chemical carcinogen on the endoplasmic reticulum in vivo and in vitro]. AB - The results of a comparative biochemical and electron-microscopic study of membrane-injuring effect of N-nitrosodimethylamine--a chemical carcinogen widespread in the environment are reviewed. It has been established that in vivo and in vitro membrane-injuring effect of nitrosodimethylamine is characterized by reduced activity of membrane-bound enzymes of endoplasmic reticulum (UDP glucuronyltransferase and glucose-6-phosphatase) accompanied by alterations in functional morphology of cells and intracellular structure. PMID- 3101764 TI - Plasminogen activator inhibitor: a regulator of ancrod-induced fibrin deposition in rabbits. AB - Plasma levels of a fast-acting plasminogen activator inhibitor (PAI), which neutralizes both tissue plasminogen activator (t-PA) and urokinase, are markedly increased in endotoxin-treated rabbits. The ability of this inhibitor to prevent the fibrinolysis that occurs after a thrombogenic stimulus was investigated in a rabbit model. Normal and endotoxin-treated male New Zealand rabbits were infused with ancrod, an enzyme that causes noncrosslinked fibrin formation in vivo. Ancrod stimulated t-PA activity by 90% in normal rabbits and caused hypofibrinogenemia but did not increase PAI levels or induce fibrin deposition in target organs. Rabbits injected with endotoxin (10 micrograms/kg) showed an increase in PAI from less than 1 to 32 U/mL 4 hours later. When ancrod was infused at this time, 90% of the rabbits developed renal fibrin thrombi. Fibrin deposition was recorded in 40% of the rabbits that received a lower dose of endotoxin (1.0 microgram/kg) and had a PAI level of 14 U/ml at the time of ancrod infusion 4 hours later. Fibrin deposition did not occur in the endotoxin-treated rabbits that received normal saline. These data suggest that high levels of PAI inhibit fibrinolysis in vivo, thereby promoting fibrin clot deposition following a thrombogenic stimulus. PMID- 3101763 TI - Initial experience in treating human lymphoma with a chimeric univalent derivative of monoclonal anti-idiotype antibody. AB - Murine monoclonal anti-idiotype antibody was raised against the surface IgM on the neoplastic cells of a patient with widespread follicular lymphoma. For therapy, a chimeric antibody derivative, FabIgG, was constructed by thioether linking Fab'gamma, from the monoclonal antibody, to human normal IgG. FabIgG is univalent and thereby avoids rapid antigenic modulation. Its human IgG component is intended to optimize recruitment of effectors and metabolic survival while minimizing immunogenicity. Four intravenous (IV) infusions of 380 to 580 mg of anti-idiotype FabIgG were given over a period of 11 weeks. There was no significant toxicity. On each occasion, the antibody disappeared from the plasma with a half-life (t1/2) of less than 24 hours. The brief survival was evidently due to uptake by tumor, as infused control FabIgG, containing Fab'gamma from an irrelevant antibody, yielded a plasma t1/2 of greater than 10 days. With each therapeutic infusion, there was a fall in the number of circulating neoplastic cells over a 24-hour period. The numbers were largely replenished over the next week, but a net fall became discernible over the entire period of treatment. Four days after each infusion, nodal masses were swollen and tender, subsiding over approximately 8 days. At the end of the treatments, the blood lymphocyte count and nodal and splenic swellings continued to subside, so that by 6 weeks a partial remission with removal of greater than 50% of tumor was judged to have occurred. We did not detect any qualitative change in surface idiotype nor any antibody response to the infused Ig. PMID- 3101765 TI - Human neutrophil elastase alters human alpha-thrombin function: limited proteolysis near the gamma-cleavage site results in decreased fibrinogen clotting and platelet-stimulatory activity. AB - During blood coagulation, polymorphonuclear leukocytes release elastase in amounts that can exceed 100 nmol/L. We therefore studied the interaction between human leukocyte elastase and human alpha-thrombin. Elastase cleaved the thrombin B chain (Ala 150-Asn 151) near the gamma-cleavage site, resulting in two fragments held together by noncovalent interactions. The NH2-terminal fragment (FI), mol wt approximately 18,000, was disulfide-linked to the thrombin A chain. The COOH-terminal fragment (FII), mol wt approximately 13,000, contained the active-site serine and formed a covalent bond with antithrombin III. Heparin accelerated proteolysis of alpha-thrombin by elastase. Proteolyzed alpha-thrombin (T theta) retained full amidolytic activity; however, the concentration of T theta causing 50% maximal platelet aggregation and adenosine triphosphate (ATP) release was 7.9 nmol/L (1.1 nmol/L for alpha-thrombin and 220 nmol/L for gamma thrombin). Fibrinogen clotting activity of T theta and gamma-thrombin was 32% and 1% that of alpha-thrombin, respectively. Elastase released during the coagulation process may modulate thrombin activity. In addition, elastase-modified thrombin may be a useful probe of the structure and function of the gamma-cleavage region. PMID- 3101766 TI - Value of monoclonal anti-CD22 (p135) antibodies for the detection of normal and neoplastic B lymphoid cells. AB - Two monoclonal antibodies (To15 and 4KB128) specific for the B cell-associated CD22 antigen (135,000 mol wt) are described. On immunoenzymatic analysis of cryostat tissue sections, these antibodies strongly label both mantle zone and germinal center B lymphoid cells in secondary lymphoid follicles (and also scattered extrafollicular lymphoid cells) but are unreactive with other cell types (with the exception of weak reactivity with some epithelioid histiocytes). These reactions differ from those of monoclonal antibodies B1 and B2 (anti-CD20 and CD21) but are similar to those of the pan-B antibody B4 (anti-CD19). One of the anti-CD22 antibodies (To15) has been tested extensively by immunoenzymatic labeling on greater than 350 neoplastic lymphoid and hematological samples. The CD22 antigen was found in tissue sections in most B cell-derived neoplasms, the major exceptions being myeloma (all cases negative) and a small proportion of high-grade lymphoma (6% of cases negative). In cell smears, the antigen could be found on neoplastic cells in most B cell lymphoproliferative disorders, including common acute lymphoblastic leukemia (ALL) (90% positive) and B cell chronic lymphocytic leukemia (CLL) (89% positive). We conclude that anti-CD22 antibodies are of value for identification of human B cell lymphoproliferative disorders (especially when used in conjunction with anti-CD19 antibodies). Previous reports that the CD22 antigen is absent from many B cell neoplasms are probably due to its being expressed within the cytoplasm of immature B cells rather than on their surface. PMID- 3101767 TI - T cell differentiation stages identified by molecular and immunologic analysis of the T cell receptor complex in childhood lymphoblastic leukemia. AB - T cell differentiation was investigated by determining the relationship of T cell receptor (Ti) gene rearrangement and transcription to the expression of surface and cytoplasmic T3 antigen using blast cells from five children with acute lymphoblastic leukemia of thymic origin. Patterns of monoclonal antibody (MoAb) reactivity indicated that these cases were representative of the three recognized stages (I, II, III) of human thymocyte development. The T3 antigen, which becomes linked to the Ti to form a functional T cell receptor complex on mature thymocytes, was expressed on the cell surface in two cases (stage III). However, in the remaining three cases that were surface T3 negative (stages I and II), large amounts of T3 were identified in the cytoplasm by immunoperoxidase staining and flow cytometry. Leukemic blasts from all five patients showed rearranged genes encoding the beta-chain portion of the Ti heterodimer. RNA transcripts of Ti beta-chain genes were also evident in lymphoblasts from all five cases, but transcripts coding for the alpha-chain portion of Ti were found only in cases that expressed T3 on the cell surface. Thus the absence of surface T3 (and presumably Ti) coincides with the absence of Ti alpha-chain RNA, suggesting that transcription of alpha-chain genes is a critical regulatory event in the surface expression of the Ti-T3 complex. Leukemic T cells that rearrange and express Ti beta-chain genes but lack Ti alpha-chain messenger RNA (mRNA) may represent a stage of differentiation analogous to pre-B cells, where heavy-chain immunoglobulin (Ig) genes are rearranged and expressed but light-chain Ig genes are not expressed. PMID- 3101768 TI - Differences in coagulant and fibrinolytic activities of cultured human endothelial cells derived from omental tissue microvessels and umbilical veins. AB - Large vessel and microvascular endothelial cells were compared in their capacity to synthesize and secrete coagulant and fibrinolytic factors. Human omental tissue microvascular endothelial cells (HOTMEC) and human umbilical vein endothelial cells (HUVEC) were isolated, grown to confluency under identical conditions, and studied in primary cultures. After an incubation period of 12 hours in serum-free medium, the conditioned medium of confluent HOTMEC contained 100-fold higher levels of tissue plasminogen activator (tPA) antigen than that of HUVEC. The conditioned media as well as the lysates of both cell types did not contain any free tPA activity, but the free plasminogen activator inhibitor capacity was found intracellularly as well as extracellularly. Although von Willebrand factor was detected in both cell types by immunofluorescence, measurable amounts were only found in HUVEC using an enzyme-linked immunosorbent assay. The kinetics of protein C activation by thrombin on the surface of once passaged cells were identical for HOTMEC and HUVEC. The present study indicates that cultivated HOTMEC produce larger quantities of tPA than HUVEC do, possess smaller amounts of von Willebrand factor than HUVEC do, and express thrombomodulin for protein C activation as effectively as HUVEC. PMID- 3101770 TI - Effects of carbaryl on differentiated and undifferentiated neuroblastoma cells: inhibition of growth rates and direct cell toxicity. PMID- 3101769 TI - bcr-abl RNA in patients with chronic myelogenous leukemia. AB - The major consequence of the formation of the Philadelphia (Ph1) chromosome characteristic of leukemia cells of patients with chronic myelogenous leukemia (CML) is fusion of c-abl and bcr genes. Using a sensitive RNase protection technique, we analyzed mRNA from a large number of CML patients. In most, we identified one or both species of bcr-abl chimeric transcripts. These two mRNAs vary in the specific bcr exon joined to abl exon II and are translated into slightly different proteins. The amounts of the fused mRNA within leukemia cells vary considerably between individuals and do not correlate with the phase of the disease. PMID- 3101771 TI - Hydrazine degradation and its effect on microbial activity in soil. PMID- 3101772 TI - Brain cholinesterase activity of rainbow trout poisoned by carbaryl. PMID- 3101773 TI - Polycyclic aromatic hydrocarbon metabolism in mullets, Chelon labrosus, treated by polychlorinated biphenyls. PMID- 3101774 TI - Uptake of polychlorinated biphenyls (PCBs) by the macroalga, Cladophora glomerata. PMID- 3101775 TI - Photodegradation of decachlorobiphenyl. PMID- 3101776 TI - Unanswered questions on neural tube defects. PMID- 3101777 TI - Reproduction of epigastric pain of duodenal ulceration by adenosine. AB - Intravenous boluses of adenosine produced transient epigastric discomfort indistinguishable from spontaneous pain in five of six patients with endoscopically confirmed duodenal ulcer, an effect which was slightly but significantly antagonised by aminophylline. These findings may be relevant to the pathophysiology of peptic ulcer pain. PMID- 3101778 TI - Doppler studies in the growth retarded fetus and prediction of neonatal necrotising enterocolitis, haemorrhage, and neonatal morbidity. AB - In 82 consecutive cases of intrauterine growth retardation managed by established criteria fetal Doppler studies identified 29 fetuses with absence of end diastolic frequencies in the fetal aorta. These same fetuses were significantly more growth retarded (p less than 0.001) and had an earlier gestational age at delivery (p less than 0.001) than those with end diastolic frequencies present. A subgroup of these cases was analysed in more detail to examine the prognostic value of this phenomenon for the neonate. Two groups of neonates of equivalent gestational age and with a birth weight below 2000 g were compared. There were 26 neonates with absent end diastolic frequencies (group 1) and 20 with end diastolic frequencies (group 2) in the fetal aorta. Those in group 1 were more likely to suffer perinatal death (p less than 0.05), necrotising enterocolitis (p less than 0.01), and haemorrhage (p less than 0.05). Only 4 (15%) of the babies in group 1 had an uncomplicated neonatal period compared with 15 (75%) in group 2 (p less than 0.001). The circulatory changes identified in these cases may provide a more sensitive measure of critical fetal compromise than current techniques and thus allow the clinician to deliver the fetus before irreversible tissue damage has occurred. PMID- 3101780 TI - Medicine and managers. PMID- 3101779 TI - Snoring as a risk factor for ischaemic heart disease and stroke in men. AB - The association of snoring with ischaemic heart disease and stroke was studied prospectively in 4388 men aged 40-69. The men were asked, in a questionnaire sent to them, whether they snored habitually, frequently, occasionally, or never. Hospital records and death certificates were checked for the next three years to establish how many of the men developed ischaemic heart disease or stroke: the numbers were 149 and 42, respectively. Three categories of snoring were used for analysis: habitual and frequent snorers (n = 1294), occasional snorers (n = 2614), and non-snorers (n = 480). The age adjusted relative risk of ischaemic heart disease between habitual plus frequent snorers and non-snorers was 1.91 (p less than 0.01) and for ischaemic heart disease or stroke, or both, 2.38 (p less than 0.001). There were no cases of stroke among the non-snorers. Adjustment for age, body mass index, history of hypertension, smoking, and alcohol use did not significantly decrease the relative risks, which were 1.71 (p greater than 0.05) for ischaemic heart disease and 2.08 (p less than 0.01) for ischaemic heart disease and stroke combined. At the beginning of follow up in 1981, 462 men reported a history of angina pectoris or myocardial infarction. For them the relative risk of ischaemic heart disease between habitual plus frequent snorers and non-snorers was 1.30 (NS); for men without previous ischaemic heart disease 2.72 (p less than 0.05). Snoring seems to be a potential determinant of risk of ischaemic heart disease and stroke. PMID- 3101781 TI - Safety and efficacy of nimodipine in resuscitation of patients outside hospital. PMID- 3101783 TI - Campylobacter enteritis in young children living in households with puppies. PMID- 3101782 TI - Poverty and teenage pregnancy. PMID- 3101784 TI - Lean body mass and non-rapid eye movement sleep. PMID- 3101785 TI - What is a good GP? PMID- 3101786 TI - Evaluation of the efficacy and acceptability to patients of a physiotherapist working in a health centre. AB - The records of the first 805 patients who had been referred by general practitioners at this health centre to the attached physiotherapist were examined in November 1985, three years after the physiotherapy department was opened. Seventy per cent (549) of the patients had been treated within one week, treatment having started on the same day for 8.5% (67) of the patients. This compares with a mean of six weeks for direct access to a district general hospital that is eight miles away and between six and 13 months for the three nearest orthopaedic consultants who are 13 miles away. The most common conditions treated were knee injuries (16.5%), followed by cervical (15.5%) and shoulder (13.8%) injuries. Surprisingly, only 9% were back injuries. The non-attendance rate was 2.2% and only 7% of patients failed to complete treatment. Nearly all the patients were able to attend the clinic, only 4% requiring home treatment. By March 1986, 90 treatments a week were being carried out at a cost of 6.11 pounds per patient. Compared with official hospital figures, this represents a savings of 21,500 pounds a year for a practice of 12,000 patients. PMID- 3101787 TI - Detection of abnormality of fetal urinary tract as a predictor of renal tract disease. AB - Over three years all infants in this hospital found to have an abnormality of the urinary tract on antenatal scanning were followed up after delivery with contrast radiography. Disease of the renal tract was confirmed in 17 of 20 infants. Of the 15 survivors, 12 underwent surgery in the first year of life. Abnormality of the fetal urinary tract detected by ultrasound scanning seems to be an important indicator of disease of the renal tract. Before its use is extended, however, further assessment of the benefit of antenatal diagnosis and of the best time to scan is required. PMID- 3101788 TI - Dermatological conditions in HIV infection. PMID- 3101789 TI - Haematology, ethnography, and thrombosis. PMID- 3101790 TI - Controlled trial of a new cervical spatula. AB - A wooden spatula was designed to scrape the varied distribution of epithelial abnormalities of the cervix as seen at colposcopy. The efficiency of the spatula in obtaining dyskaryotic cells and improving the cellular quality of smears was compared with that of the Ayre spatula in a controlled trial. More than 17,000 smears were taken from women aged 14-86 years by more than 200 smear takers from 74 centres. Twenty two per cent more dyskaryotic smears were obtained with the trial spatula, and the cellular quality of the smears was improved in all age groups. Although it was associated with a slightly increased risk of bleeding, 83% of users preferred the trial spatula. PMID- 3101791 TI - Psychosexual problems. PMID- 3101793 TI - Antibiotics. PMID- 3101792 TI - Coffee, cholesterol, and colon cancer: is there a link. PMID- 3101794 TI - Portraits from memory. 1--Fifty years of microbiology: first steps. PMID- 3101795 TI - AIDS publicity: some experiences from Scotland. PMID- 3101797 TI - Asthma mortality: comparison between New Zealand and England. PMID- 3101796 TI - HIV and sexual lifestyle. PMID- 3101798 TI - Hazard of potassium chloride solution. PMID- 3101799 TI - Continuous ambulatory peritoneal dialysis. PMID- 3101800 TI - Prognosis for infants born at 23 to 28 weeks' gestation. PMID- 3101801 TI - Prolonged pregnancy. PMID- 3101802 TI - Prevalence of HBsAg in UK population. PMID- 3101803 TI - AIDS: a doctor's duty. PMID- 3101804 TI - Tranexamic acid as an aid to reducing blood transfusion requirements in gastric and duodenal bleeding. AB - A prospective randomised double blind study examined the effect of the antifibrinolytic drug tranexamic acid compared with placebo in 154 patients bleeding from verified benign lesions in the stomach or duodenum or both. Three out of 72 patients receiving tranexamic acid underwent emergency surgery compared with 15 out of 82 given placebo (p = 0.010). Nineteen patients receiving placebo rebled during their admission as compared with 10 in the active treatment group (p = 0.097). Blood transfusion requirements were significantly reduced by tranexamic acid (p = 0.018). Side effects occurred in six patients, of which an uncomplicated deep venous thrombosis was the most severe. Tranexamic acid reduces the blood transfusion requirement and need for emergency surgery in patients bleeding from a benign gastric or duodenal lesion. PMID- 3101805 TI - Time for action on hepatitis B immunisation. PMID- 3101806 TI - The locked in syndrome. PMID- 3101807 TI - Black-white health gap in the USA. PMID- 3101808 TI - Real and imaginary halitosis. PMID- 3101809 TI - When a woman asks for a caesarean section. PMID- 3101810 TI - Time, gentlemen, please ... PMID- 3101811 TI - Family therapy. PMID- 3101812 TI - Phototherapy and dithranol treatment of psoriasis: new lamps for old. AB - The response of psoriasis to ultraviolet radiation and dithranol was compared with the response to dithranol alone in 24 patients. The difference in rate of response, measured as change in plaque thickness, and the difference in time to complete clearance of psoriasis between irradiated and non-irradiated forearm lesions was significantly greater for patients treated using fluorescent lamps with negligible ultraviolet C emission (Wolff Helarium) than for those patients treated with a medium pressure mercury arc lamp (p less than 0.01) or an array of fluorescent sunlamps (p less than 0.05). The difference in therapeutic response shows that ultraviolet B phototherapy is effective when used in combination with dithranol. Nevertheless, radiation sources with substantial ultraviolet C emission, such as the medium pressure mercury arc lamp most commonly used to treat psoriasis in the United Kingdom, have little effect because delivery of therapeutic doses of ultraviolet B is limited by erythema induced by ultraviolet C. PMID- 3101813 TI - Non-secretion of ABO blood group antigens as a host susceptibility factor in the spondyloarthropathies. AB - Gram negative bacteria precipitate reactive arthritis and may be concerned in the pathogenesis of ankylosing spondylitis and other spondyloarthropathies. Susceptibility to many infectious agents is associated with ABO blood group or secretor state, or both. The distribution of the ABO blood group or secretor state, or both, was therefore determined in 87 patients with ankylosing spondylitis and 32 with other forms of spondyloarthropathy. The prevalence of non secretors was significantly increased in the total patient group (54/114; 47%) and in the subgroup with ankylosing spondylitis (41/84; 49%) compared with local controls (89/334; 27%) (p less than 0.001). Other subgroups of patients showed a similarly increased prevalence of non-secretion (33-47%). The distribution of ABO blood groups did not differ between patients and controls. The association between non-secretor state and ankylosing spondylitis strengthens the hypothesis that ankylosing spondylitis is a form of reactive arthritis. It also suggests several pathogenic mechanisms which may be relevant to the initial hostparasite interaction in ankylosing spondylitis. PMID- 3101815 TI - Psychiatric disorder and gynaecological symptoms in middle aged women: a community survey. AB - In a community survey 521 women aged 35-59 were selected at random from all patients registered in two groups practices. They were interviewed at home and assessed by means of standardised psychiatric measures and detailed gynaecological inquiry. Levels of psychiatric morbidity were found to be within the expected range for such a sample. Both psychiatric morbidity and the personality dimension of neuroticism were significantly associated with gynaecological symptoms, including dysmenorrhoea and premenstrual tension, some symptoms of excessive menstruation, and flushes and sweats but not disappearance of menstruation for over six months. Current psychiatric state was significantly associated with recent adverse life events and with indices of psychiatric vulnerability (neuroticism and previous psychiatric history), suggesting possible aetiological links with gynaecological symptoms. The findings of this study have implications for the management of gynaecological complaints in general practice. PMID- 3101816 TI - Frequency, sequence, and side of ovulation in women menstruating normally. PMID- 3101814 TI - Prognosis of children who are carriers of hepatitis B. AB - Fifteen children who had become positive for hepatitis B surface antigen (HBsAg) by perinatal transmission were traced and re-examined after a mean of 8.1 years; all had been born in England to mothers from ethnic minorities who were carriers of HBsAg. Fourteen of the children remained carriers of HBsAg; of these, more girls than boys developed antibody to hepatitis B e antigen (anti-HBe). Those children whose transaminase activities had been above normal within the first three years of life were more likely to have developed anti-HBe. The earlier production of anti-HBe suggests that girls have a more effective immune response. Increased transaminase activity early in the course of asymptomatic carriage of HBsAg may be a favourable prognostic sign. PMID- 3101817 TI - Depression and outcome in acute myocardial infarction. PMID- 3101818 TI - Henoch-Schonlein purpura associated with Legionnaires' disease. PMID- 3101819 TI - Successful liaison between the health team and social workers in Blackburn, West Lothian. PMID- 3101820 TI - Completeness of chronic disease registration in general practice. AB - The completeness of chronic disease registration in four general practices was assessed by referring to the Hospital Activity Analysis. Overall, just over half (56%) of the 695 patients who had been discharged from hospital with a diagnosis of diabetes, cancer, myocardial infarction, epilepsy, hypertension, or thyroid disease were identified on the practice disease registers. Patients with diabetes were most likely to be identified (72%), and those who had had a myocardial infarct least likely (43%). If the standard of registration is to be improved general practitioners must be convinced of its value. The Hospital Activity Analysis might be used widely to audit and improve practice registers. PMID- 3101821 TI - Controlled trial of respiratory health worker visiting patients with chronic respiratory disability. AB - Seventy five patients with chronic respiratory disability were randomised to a group visited by a respiratory health worker (42) or control group (33). The first group was visited monthly by a respiratory nurse, who gave education and support. The effect of the intervention was assessed in terms of quality of life (by questionnaires), the number and duration of admissions to hospital, and the number of deaths. The questionnaires on quality of life showed no changes in either group during the study, but nearly all of the group visited by a respiratory health worker said that they valued the visits and wished them to continue. Their knowledge about their condition also improved compared with that of the controls. The duration of stay in hospital for respiratory reasons in the group visited by a respiratory health worker was longer than that of control patients. This was explained by their being scored as more ill than the controls on admission. Fewer patients died in the group visited by a respiratory health worker than in the control group (p = 0.11). The patients in the group visited by respiratory health workers may have survived longer because they sought help rather than dying at home. If confirmed this could have implications for the cost of their care. PMID- 3101822 TI - Early emergency care study: the potential and benefits of advanced prehospital care. AB - Of 26358 patients taken by ambulance to the accident and emergency departments of two large hospitals, 1185 were admitted to resuscitation areas. The scope for ambulance staff to employ a range of advanced techniques at the scene of incidents was assessed by using information relating to the condition of patients when they were picked up by the ambulance and on admission, time in transit, details from hospital records, and outcome at three months. For non-survivors further assessment was made of the benefit, in terms of survival, which might have accrued had advanced techniques been used. The results of the assessment of benefit were compared with estimates of benefit from other studies. In cases of cardiopulmonary arrest the potential to save lives was less optimistic than earlier estimates, and in cases of trauma the potential to save lives was negligible. PMID- 3101823 TI - Portraits from memory. 4--Sir Hector Hetherington, GBE (1888-1965). PMID- 3101824 TI - Anaesthesia and the flying surgeon service 25 years on. PMID- 3101826 TI - History says no to the policeman's response to AIDS. PMID- 3101827 TI - AIDS: a doctor's duty. PMID- 3101825 TI - Treatment of rheumatic diseases. PMID- 3101828 TI - Haematology, ethnography, and thrombosis. PMID- 3101829 TI - Dialysis arthropathy: amyloid or iron? PMID- 3101830 TI - Hazard of potassium chloride solution. PMID- 3101831 TI - Dangers in treating hyponatremia. PMID- 3101832 TI - Restless legs syndrome. PMID- 3101833 TI - Measuring morbidity. PMID- 3101834 TI - Thyroid disease in pregnancy. PMID- 3101835 TI - How useful a diagnosis is borderline personality disorder? PMID- 3101836 TI - The General Practice Finance Corporation: an unnecessary change. PMID- 3101837 TI - Nuclear DNA analysis of koilocytic and premalignant lesions of the uterine cervix. AB - Cervical biopsy samples were taken from 79 patients who had various grades of cervical intraepithelial neoplasia or who showed evidence, in the form of koilocytosis, of human papillomavirus infection of the uterine cervix and from 10 women with normal cervices. The DNA content of the cells in the samples was analysed by flow cytometry. Analysis of the data obtained showed that the biopsy samples from women with cervical intraepithelial neoplasia and human papillomavirus lesions contained significantly more dividing cells (31.2% of cells from human papillomavirus lesions with no cervical intraepithelial neoplasia and 33.06%, 29.89%, and 31.76% of cells from cervical intraepithelial neoplasia grades I, II, and III, respectively) than those from women with normal cervices (21.6%). The proportion of aneuploid samples from the group who showed evidence of human papillomavirus infection only (18.2%) did not differ significantly from the group with cervical intraepithelial neoplasia grade III (21.2%). Aneuploidy and an increased rate of cellular proliferation are recognised characteristics of malignancy. These results therefore support the view that human papillomavirus plays an important part in the aetiology of cervical carcinoma and are relevant to the clinical management of patients. PMID- 3101838 TI - Increased saliva oestriol to progesterone ratio before preterm delivery: a possible predictor for preterm labor? AB - Saliva oestriol, oestradiol, and progesterone concentrations were measured in 23 women who went into spontaneous preterm labour. The patients fell clinically and biochemically into two groups. The 13 who went into preterm labour with intact membranes had a saliva oestriol to progesterone ratio greater than one in every case and greater than the 95th centile for their length of gestation in 12 cases; by contrast, all those who went into spontaneous preterm labour after prolonged rupture of the membranes had an oestriol to progesterone ratio less than one and below the 50th centile for their period of gestation in the one to four days before delivery. Saliva oestradiol to progesterone ratios were randomly distributed throughout the normal range in both groups. It appears that preterm labour without prior prolonged rupture of the membranes is, like term labour, preceded by an increase in the saliva oestriol to progesterone ratio. It may therefore be possible to use this ratio to predict preterm labour. PMID- 3101839 TI - Impact of gestrinone on the course of asymptomatic endometriosis. AB - A new drug, gestrinone, was subjected to the first double blind, randomised placebo controlled trial of any treatment of endometriosis. The disease deteriorated in eight (47%) of the 17 patients prescribed placebo (95% confidence limits 23% and 71%) compared with none of the 18 patients prescribed gestrinone (p = 0.002). There was a difference in elimination of the endometriosis in the gestrinone group compared with placebo but this was not statistically significant (p = 0.057). There was a significant difference in improvement of the disease in the gestrinone group compared with placebo (p = 0.004), confirming that gestrinone is an effective treatment of endometriosis. Endometriosis deteriorates in at least 23% of patients; as it is impossible to predict in whom this will happen, treatment appears to be warranted in all cases. PMID- 3101840 TI - Increased incidence of true type I diabetes acquired during pregnancy. AB - A longitudinal study was carried out of all patients with newly acquired insulin dependent diabetes during pregnancy (as distinct from non-insulin-dependent gestational diabetes) seen at the Copenhagen Centre for Diabetes and Pregnancy during 1966 to 1980. The series comprised 63 patients with a mean age of 27 (SEM 1) years. At diagnosis the mean fasting blood glucose concentration was 15.6 (1.3) mmol/l and mean maximal insulin dose 49 (3) IU/day. At a prospective follow up examination a mean of 8 (SEM 1) years after diagnosis 46 of 60 patients (77%) were being treated with insulin (35 (2) IU/day) and had a very low mean stimulated plasma C peptide value (0.12 (0.02) nmol/l) suggesting absent or nearly absent beta cell function. The remaining 14 patients (23%), not currently receiving insulin, appeared to be severely glucose intolerant, having a mean fasting blood glucose concentration of 13.4 (1.2) mmol/l. Thus most of these patients developing insulin dependent diabetes during pregnancy had true type I disease. Compared with the age specific incidence of type I diabetes in the background population of women the incidence was at least 70% higher in pregnant than non-pregnant women (p less than 0.001; chi 2 = 11.6; f = 1). This increased incidence occurred in the third trimester when the risk of developing type I diabetes was 3.8 times that of non-pregnant women (p less than 0.000001; chi 2 = 35.6; f = 1). Finally, the risk of developing insulin dependent diabetes during pregnancy was lower when conception occurred in the winter (p less than 0.05; chi 2 = 4.18; f = 1). PMID- 3101841 TI - Prevalence of asthma and hay fever in England and Wales. AB - The results concerned with the prevalence of asthma and hay fever in the large surveys of morbidity in general practice in 1970-1 and 1981-2 were compared. In data standardised for age the prevalence of asthma in men increased from 11.6 to 20.5 people consulting per 1000 population (p less than 0.001) and in women from 8.8 to 15.9 per 1000 population (p less than 0.001). Similar increases were also evident in data analysed from the 19 practices contributing to both surveys. The prevalence of asthma increased in each age group examined. Increases of similar magnitude were reported for hay fever--the prevalence in men increased from 10.8 to 19.8 people consulting per 1000 population (p less than 0.001) and in women from 10.3 to 19.7 per 1000 population (p less than 0.001) and occurred in all age groups. The prevalence of acute bronchitis was reduced significantly in the age group 5-14 and increased among the elderly. The prevalence of chronic bronchitis was reduced substantially in 1981-2. The reported increased prevalence of both asthma and hay fever represented a real increase and was not accounted for by changes in diagnostic preference. Only in the age group 5-14 was there any likelihood that some of the increased prevalence of asthma might have resulted from a reduction in the prevalence of acute bronchitis. PMID- 3101842 TI - Atrial fibrillation precipitated by acute hypovolaemia. AB - Six patients with varying degrees of acute cardiorespiratory failure were seen. All patients deteriorated noticeably when rapid atrial fibrillation developed. In all patients intravenous digitalis failed to slow the ventricular response, and in three patients misguided attempts at electrical cardioversion failed. Haemodynamic monitoring showed a normal or low pulmonary artery occlusion pressure in all patients. Controlled expansion of plasma volume was associated with an immediate slowing of the heart rate in all patients, and the heart rate in all patients returned to sinus rhythm within 30 minutes of transfusion. It is suggested that hypovolaemia in critically ill patients may contribute to the development of atrial fibrillation. PMID- 3101843 TI - Penetration of pyrazinamide into the cerebrospinal fluid in tuberculous meningitis. PMID- 3101844 TI - Falsely high peak expiratory flow readings due to acceleration in the mouth. PMID- 3101845 TI - Iatrogenic hypothyroidism and postpartum hyperthyroidism in familial dysalbuminaemic hyperthyroxinaemia. PMID- 3101846 TI - What is a good GP? PMID- 3101847 TI - Prospective study of drug reporting by general practitioners for an elderly population referred to a geriatric service. AB - A prospective study was carried out in which the drug history of patients which was provided by general practitioners was compared with the drugs found by geriatricians in patients' homes in 700 referrals to geriatricians. Drug compliance was not assessed. The drug history appeared to be accurate in one third of referrals. Underreporting of medication was common and increased as the number of prescribed drugs increased. Roughly one fifth of patients had at least one potential drug interaction. Keeping careful prescription records, regular review, and accurate reporting of medication should reduce drug associated morbidity in elderly patients. PMID- 3101848 TI - Can the use of radiography of arms and legs in accident and emergency units be made more efficient? AB - The efficiency of the selection of patients with injured arms and legs for radiography was investigated. The analysis was based on data on presenting signs and symptoms collected in a multicentre study organised by the Royal College of Radiologists working party on the effective use of diagnostic radiology. The work was carried out in eight accident and emergency units in England and Wales. With the help of various computer simulation techniques a combination of signs and symptoms that might usefully improve present practice was sought. The results suggest that for injuries of arms and legs the clinical determinants of bony injury cannot be refined further to improve current selection for radiography. This study shows that existing clinical practice is probably as good as it can be. PMID- 3101849 TI - Vitamin A supplements and mortality related to measles: a randomised clinical trial. AB - One hundred and eighty children admitted with measles were randomly allocated to receive routine treatment alone or with additional large doses of vitamin A (200,000 IU orally immediately and again the next day). Baseline characteristics of the two groups were virtually identical for age, severity of measles, and vitamin A and general nutritional states. In 91% of the children serum vitamin A concentrations were less than 0.56 mumol/l. Of the 88 subjects given vitamin A supplements, six (7%) died; of the 92 controls, 12 (13%) died (p = 0.13). This difference in mortality was most obvious for children aged under 2 years (one death out of 46 children receiving supplements versus seven deaths out of 42 controls; p less than 0.05) and for cases complicated by croup or laryngotracheobronchitis. Mortality was several times higher in marasmic than in better nourished children, regardless of study allocation (p less than 0.01). PMID- 3101850 TI - Treatment of endocrine diseases. PMID- 3101852 TI - Safeguarding the blood supply. PMID- 3101851 TI - Portraits from memory. 5--Professor George M Wishart (1895-1958). PMID- 3101853 TI - Acyclovir and pregnancy. PMID- 3101855 TI - Urinary frequency and urgency. PMID- 3101854 TI - Simple analgesics in pregnancy. PMID- 3101856 TI - Neurological consequences of hypomagnesaemia. PMID- 3101857 TI - The need for redistribution of training posts in psychiatry. PMID- 3101858 TI - Patient load and medical staffing in adult dialysis units in the United Kingdom. PMID- 3101859 TI - Head injuries in the elderly. PMID- 3101860 TI - Why doctors must grapple with health economics. PMID- 3101861 TI - The third heart sound. PMID- 3101862 TI - Prejudice against doctors and students from ethnic minorities. PMID- 3101863 TI - Osteoporosis: cause and management. PMID- 3101864 TI - Reye's syndrome: assessment of intracranial monitoring. AB - Direct measurements of arterial blood pressure and intracranial pressure were recorded in 39 patients aged 3.6 months to 5 years 11 months with Reye's syndrome judged to be stage 2 or beyond. Of 33 patients who survived, 27 made a full recovery and six were severely handicapped. Measurement of cerebral perfusion pressure, which is greatly reduced in the more severe forms of Reye's syndrome, was a better guide to prognosis and management than intracranial pressure alone. The findings emphasise that maintenance of cerebral perfusion pressure is essential if mortality and morbidity are to be reduced. Intracranial monitoring is mandatory in all but the mildest cases of Reye's syndrome. PMID- 3101865 TI - Economic consequences of postinfarction prophylaxis with beta blockers: cost effectiveness of metoprolol. AB - Treatment with certain beta adrenoceptor blocking agents after myocardial infarction reduces mortality and the incidence of reinfarction. Data from a randomised placebo controlled study of the beta 1 selective blocker metoprolol given as secondary prophylaxis were therefore analysed for the possible cost effectiveness of extending this treatment to the general population of patients with myocardial infarction. Metoprolol 100 mg twice daily and matching placebo were given to 154 and 147 patients, respectively, for three years. During this period drug costs for the beta blocker, digitalis, and diuretics were analysed as well as costs of readmission for cardiac problems and indirect costs arising from sick leave or early retirement. Active treatment with metoprolol significantly reduced costs of readmission as well as indirect costs. The net effect per patient over the three years was a reduction of roughly kr 19,000 (1930 pounds). These results suggest that beta blocker treatment given as secondary prophylaxis after myocardial infarction is highly cost effective. PMID- 3101867 TI - Comprehensive care of patients with head injuries. AB - The comprehensive head injury service run by the neurosurgeons at the Hull Royal Infirmary for the surrounding population of one million was analysed. The analysis showed that all patients with either a fractured skull or a lowered level of consciousness should be admitted to a district general hospital because the associated risk of their having a major head injury is over 20%. Those patients with both a fractured skull and a lowered level of consciousness have a 60% likelihood of a major head injury and should be transferred immediately to the neurosurgical unit. Patients with compound or complicated fractures of the skull and those without fractured skulls but with neurological impairment persisting for four hours or more, should also be transferred to the neurosurgical unit. If these guidelines are followed about 200 patients/million population will be referred to the neurosurgical centre. Patients with a minor head injury and none of the clinical risk factors may safely be sent home. This should reduce the rate of admissions to hospital for head injuries by 60%. PMID- 3101866 TI - Type I (insulin dependent) diabetes: a disease of slow clinical onset? AB - Type I (insulin dependent) diabetes is usually believed to present acutely and it is assumed that metabolic decompensation is sudden. In a prospective family study, however, 10 of 13 subjects developing the disease showed progressive or intermittent development of hyperglycaemia over many months and the others had non-specific symptoms over a long period. All were first degree relatives of a child with type I diabetes; 10 were siblings (aged 5-24) and three were parents (aged 45-58). All possessed HLA-DR4 or DR3, or both, and all but two had been positive for islet cell antibodies for six to 86 months before diagnosis. Ten had non-specific symptoms for two to 14 months before the onset of thirst and polyuria; one remained asymptomatic even when insulin became necessary. Six subjects had an oral glucose tolerance test before clinical onset, of whom five were diabetic by World Health Organisation criteria four, four, six, seven, and 21 months before insulin was needed. Nine showed random blood glucose concentrations above the 97.5th centile (6.3 mmol/l) six to 34 months (median 12) before diagnosis. Two others had a glucose tolerance test result compatible with diabetes but had not reached the stage of needing insulin. Hyperglycaemia is often of insidious onset in type I diabetes, even in children and young adults. Diagnosis will inevitably be late if considered only when acute symptoms of thirst and polyuria develop. PMID- 3101868 TI - Value of booster immunisation with influenza vaccine in patients undergoing haemodialysis. PMID- 3101869 TI - Neuropathy of the feet due to running on cold surfaces. PMID- 3101870 TI - Occult chlamydial ophthalmia in men with non-gonococcal urethritis. PMID- 3101871 TI - Oedema of the ileum: a possible manifestation of food allergy. PMID- 3101872 TI - What is a good GP? PMID- 3101873 TI - One thousand heart attacks in Grampian: the place of cardiopulmonary resuscitation in general practice. AB - The outcome of 1011 heart attacks in patients under the care of general practitioners who practised cardiopulmonary resuscitation and were equipped with defibrillators is reported. The 28 day mortality was 36% (367 patients), and 59% of deaths occurred outside hospital. The general practitioner was the first medical contact in 92% of heart attacks and was equipped with a defibrillator in 80% of such calls. Fifty six patients had a cardiac arrest in the presence of a general practitioner, and resuscitation was attempted in 47 cases, representing 5% of all calls for heart attacks. Twenty one (45%) resuscitated patients reached hospital alive, and 13 (28%) survived to leave hospital. The opportunities for cardiopulmonary resuscitation in general practice occur sufficiently often to warrant training and equipping general practitioners for advanced life support. The results of resuscitation by general practitioners working alone compare favourably with those of mobile coronary care units based in hospitals. PMID- 3101874 TI - Who provides patients with drug information? AB - One hundred and fifty four patients were interviewed to determine the type and source of information that they had received about drugs that had been prescribed for them. Most had been told how often to take the drugs (145 (94%)) and how much to take each time (143 (93%)), but few had been informed about side effects (49 (32%)) and fewer had received written information (22 (14%)). Pharmacists most commonly supplied information about how often to take the drugs (105 (68%)), how much to take each time (99 (64%)), and the best way to take it (109 (71%)). Doctors most often gave information about duration of treatment (116 (75)) and possible side effects (126 (82%)). Few patients requested specific information on their own initiative. More research is needed to determine how best to communicate drug information to patients. PMID- 3101875 TI - Portraits from memory. 6--Charge nurse Cecilia Scott, Belvidere Fever Hospital, Glasgow. PMID- 3101876 TI - Report from the PHLS Communicable Disease Surveillance Centre. PMID- 3101877 TI - Victorian nurses' strike. PMID- 3101878 TI - Brain abscess presenting as an intracranial gas shadow. PMID- 3101879 TI - Should we be screening for cervical cancer or breast cancer? PMID- 3101880 TI - Waiting time for urgent appointments. PMID- 3101881 TI - Methicillin resistant Staphylococcus aureus. PMID- 3101882 TI - Snoring as a risk factor for ischemic heart disease and stroke in men. PMID- 3101883 TI - Association between liberalization of Scotland's liquor licensing laws and admissions for self poisoning. PMID- 3101884 TI - Dialysis arthropathy: amyloid or iron? PMID- 3101885 TI - The increase in molluscum contagiosum. PMID- 3101886 TI - Death in the clouds. PMID- 3101887 TI - Vaccine related poliomyelitis in non-immunised relatives and household contacts. PMID- 3101888 TI - Quality of institutional care and the elderly: policy issues and options. PMID- 3101889 TI - AIDS and intravenous drug use: the real heterosexual epidemic. PMID- 3101890 TI - Treating postural hypotension. PMID- 3101891 TI - Enuresis at 25. PMID- 3101892 TI - Respiration and connective tissue diseases. PMID- 3101893 TI - Christ Church conference on postgraduate education--25 years on. PMID- 3101894 TI - Ivory Tower Inc: universities and the market place. PMID- 3101896 TI - Diabetogenic effect of cyclosporin. AB - A young woman given a renal allograft for polycystic kidney disease developed insulin dependent diabetes mellitus 25 days after transplantation. There was no family history of diabetes, plasma glucose concentrations had been normal at presentation and on five subsequent occasions, and at no time were islet cell antibodies detectable. Plasma C peptide concentrations, however, were greatly suppressed after transplantation and remained so for up to six months. The immunosuppressive regimen had included cyclosporin A, which had been difficult to regulate and caused definite signs of toxicity in the patient. By virtue of its reported toxicity for beta cells and the reversal of the diabetes several months after the dose was reduced cyclosporin was incriminated as the probable causative agent. Dose related beta cell toxicity of cyclosporin A may be a risk in recipients of this drug and warrants careful monitoring of drug and glucose concentrations. PMID- 3101895 TI - Propofol infusion for sedation in the intensive care unit: preliminary report. AB - Propofol (2,6,di-isopropylphenol) was given by continuous intravenous infusion to provide sedation after cardiac surgery in 30 patients and its effects compared with those of midazolam given to a further 30 patients. Propofol infusion allowed rapid and accurate control of the level of sedation, which was satisfactory for longer than with midazolam. Patients given propofol recovered significantly more rapidly from their sedation once they had fulfilled the criteria for weaning from artificial ventilation and as a result spent a significantly shorter time attached to a ventilator. There were no serious complications in either group. Both medical and nursing staff considered the propofol infusion to be superior to midazolam in these patients. These findings suggest that propofol is a suitable replacement for etomidate and alphaxalone-alphadolone for sedating patients receiving intensive care. PMID- 3101897 TI - Detection of venom by enzyme linked immunosorbent assay (ELISA) in patients bitten by snakes in Thailand. AB - The ability of an enzyme linked immunosorbent assay (ELISA) to detect venom was evaluated in 251 patients bitten by four of the commonest poisonous snakes in Thailand. Serum was tested only from patients who brought the snakes that had bitten them. About one third of all bitten patients had detectable venom antigenaemia, though a smaller proportion were symptomatic. Serum venom concentrations on admission correlated with the severity of clinical manifestations. The test was sensitive and specific even for specimens that had been collected and stored under suboptimal conditions. The technique is suitable for forensic use in cases of suspected snakebite. The combination of snake identification and venom antigen detection should be a more reliable means of studying the epidemiology of snakebite than the measurement of venom antibodies in a population. PMID- 3101898 TI - What contribution has cardiac surgery made to the decline in mortality from coronary heart disease? AB - The number of deaths from coronary artery disease is declining in New Zealand as in some other Western countries. It has been estimated that in 1981 in the Auckland metropolitan area there were 126 fewer deaths than would have been expected from the data in 1974. The contribution made by cardiac surgery to this decline was assessed from the known numbers of patients who were operated on, from their survival rate, and from the predicted mortality of the surgical cohort had they not undergone operation. Such mortality was predicted from past studies of patients with similar symptoms, exercise data, studies of unstable angina, and the coronary artery surgical study registry. From this method it was estimated that coronary surgery accounted for 26% to 42% of the reduction in coronary deaths. Two previous studies estimated, from calculations based on the European study of patients with modest symptoms, that the contribution of cardiac surgery was much lower. Extrapolating data from one subset of patients to a second subset with quite different characteristics is a conceptual fallacy. PMID- 3101900 TI - Renal failure and the histopathological features of myeloma kidney reversed by intensive chemotherapy and peritoneal dialysis. PMID- 3101899 TI - Psychiatric morbidity among spouses of patients with stroke. AB - The medium term psychiatric morbidity of spouses of patients with stroke was evaluated one to three years after the event. Compared with a control group the spouses were more likely to be depressed (p less than 0.005) and had more physical symptoms (p less than 0.01). Depression increased with the severity of the stroke in the spouse (p less than 0.05) and with time during the three years. Regular contact with friends and neighbours protected spouses (p less than 0.005). Depressed spouses were more likely to be taking tranquillisers than non depressed spouses (p less than 0.0001) but no more likely to be taking antidepressants. Social rehabilitation after stroke was less successful when the spouse was depressed. Proper attention paid to spouses of patients with stroke might improve the prospects of these patients. PMID- 3101901 TI - Dangers from dissolution of latex in Celestin endo-oesophageal tube. PMID- 3101902 TI - Diabetes mellitus after hypophysectomy for acromegaly. PMID- 3101903 TI - Effect of the pollen season on nasal mast cells. PMID- 3101904 TI - What is a good GP? PMID- 3101905 TI - Are the recommendations being met in the general practice year of vocational training? Trainees' views in the West Midlands region. AB - Vocational trainees in the West Midlands who were in their general practice year were sent a postal questionnaire to find out whether there were important differences between the criteria for training of the 1986 West Midland postgraduate education committee (based on national recommendations) and the perceptions of the trainees of their current trainers and practices. The response rate was 86.2% (75 out of 87). Sixty four per cent (48) of trainees reported that they received on average less than the recommended minimum of three hours of teaching time a week. They felt that experience was inadequate in paediatric surveillance (62.7%) and preventive medical care (37.3%). Most trainers gave topic teaching (90.7%), and few used role play (5%). Most of the trainees (52%) had not signed a contract, a third did not get help with recommended allowances, and 37% thought that their progress had not been reviewed. Several trainees commented on the excellence of their training practices, and most of the practices appeared to be keeping to the spirit of the recommendations. There are, however, discrepancies between what some trainees feel they receive and what is recommended. PMID- 3101907 TI - Immunisation of children by a nurse without a doctor present. AB - Over 16 months 148 children were referred by health visitors and general practitioners to a specially trained nurse for failing to complete courses of immunisation. A further 91 children of travellers' families were identified as needing immunisation. The nurse carried out 810 immunisations on 237 of these children in their homes without a doctor being present. There were only two refusals, and one child suffered a mild anaphylactic shock. The cost per immunisation, in nurse's salary and travel expenses, was pounds 8. This is an effective and fairly inexpensive way of achieving uptake of immunisation in such groups of children, and there seems no reason why trained nurses should not give immunisations either in a child health clinic or at home, without a doctor present. PMID- 3101906 TI - Hepatic reactions associated with ketoconazole in the United Kingdom. AB - Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury. PMID- 3101909 TI - The penalties of issuing misleading advertisements. PMID- 3101908 TI - Illegal abortions and the Soviet health service. PMID- 3101910 TI - Anticoagulants. PMID- 3101912 TI - The elusive orthopaedic senior house officer. PMID- 3101913 TI - Ulcerogenicity of piroxicam. PMID- 3101911 TI - Preventable blindness in giant cell arteritis. PMID- 3101914 TI - Self help groups. PMID- 3101915 TI - Dose dependent response of symptoms, pituitary, and bone to transdermal oestrogen in postmenopausal women. PMID- 3101916 TI - Lung cancer and passive smoking. PMID- 3101917 TI - Autologous blood transfusion. PMID- 3101918 TI - The Liverpool urban obstetric flying squad. PMID- 3101919 TI - Outbreak of Weil's disease in a food fad commune in India. PMID- 3101920 TI - A proposal for doing prevalence studies of AIDS. PMID- 3101921 TI - Widespread use of condoms and low prevalence of sexually transmitted diseases in Danish non-drug addicts. PMID- 3101922 TI - AIDS publicity. PMID- 3101923 TI - AIDS: a doctor's duty. PMID- 3101924 TI - Is testing for HIV without consent ever warranted? PMID- 3101925 TI - The possibility of AIDS. PMID- 3101926 TI - HIV transmitted by sexual intercourse but not by kissing. PMID- 3101927 TI - State of public health. PMID- 3101930 TI - Long-term psychiatric patients in the community. PMID- 3101928 TI - Vasodilator actions of TRK-100, a new prostaglandin I2 analogue. AB - TRK-100, a stable analogue of prostaglandin I2 (PGI2), relaxed isolated arteries of the dog precontracted with PGF2 alpha or K+; the relaxation was in the order of mesenteric and renal greater than coronary and femoral greater than basilar and middle cerebral arteries. The relaxation by TRK-100 was not affected by treatment with atropine, propranolol, cimetidine, aminophylline, and indomethacin, but was suppressed by diphloretin phosphate, a prostaglandin antagonist. Treatment with TRK-100 attenuated the contraction induced by PGF2 alpha and Ca2+ in mesenteric and basilar arteries previously exposed to Ca2+-free medium, but did not significantly alter the contractile response to Ca2+ in the arteries exposed to Ca2+-free medium and depolarized by excess K+. TRK-100 and nitroglycerin relaxed isolated mesenteric arteries to a similar extent; however, when continuously infused into mesenteric arteries in anaesthetized dogs, TRK-100 produced greater vasodilatation than nitroglycerin. It is concluded that TRK-100 relaxes dog mesenteric and renal arteries more than cerebral arteries; the relaxation appears to derive from interference with the release of Ca2+ from intracellular stores and with the transmembrane Ca2+ influx through a receptor operated channel. TRK-100 may vasodilate large and small mesenteric arteries and resistance vessels to a similar extent, whereas nitroglycerin preferentially dilates the large artery. PMID- 3101929 TI - Feedback control of arterial smooth muscle tone: the role of prostacyclin. AB - Indomethacin potentiated noradrenaline (NA)-induced contractions of rabbit isolated mesenteric arteries. Mechanical removal of the endothelium did not influence its potentiating effect. Prostacyclin (PGI2) synthesis was stimulated by NA (0.1-1.0 mumol l-1) and inhibited by indomethacin in a concentration dependent manner. There was a positive correlation between the indomethacin induced inhibition of PGI2 formation and the indomethacin-evoked potentiation of contractile responses to NA. These results suggest that endogenous PGI2 plays a part in the feedback control of vascular smooth muscle tone. PMID- 3101931 TI - Severe lactic acidosis following paraldehyde administration. PMID- 3101932 TI - Immunorestorative effect of lipid emulsions during total parenteral nutrition. PMID- 3101933 TI - History says no to the policeman's response to AIDS. PMID- 3101934 TI - Doctor's double standards on alcohol. PMID- 3101935 TI - The rise of medical English. PMID- 3101937 TI - Self help groups: the fourth estate in medicine? PMID- 3101936 TI - Restoring creativity to the dying patient. PMID- 3101938 TI - Searching for our moral roots. PMID- 3101939 TI - Three regius professors, sanitary science, and state medicine: the birth of an academic discipline. PMID- 3101940 TI - Medical students' beliefs about nine different specialties. AB - A total of 449 preclinical and postclinical students from three London University medical schools completed one of nine versions of a 50 item questionnaire seeking their attitudes to nine specialties: anaesthetics, general practice, gynaecology, hospital medicine, paediatrics, pathology, psychiatry, radiology, and surgery. There were three main findings. Firstly, though item by item analysis yielded interesting and predictable differences, such as the negative attitudes to psychiatry, the students' attitudes and beliefs were multidimensional: whereas any specialty might be seen as highly positive on one dimension--for example, effectiveness--it might be seen as highly negative on another--for example, relationships with patients. Secondly, the nine specialties seemed to be discriminative on two dimensions--soft versus hard; general versus specific--such that psychiatry was seen as soft and specific, general practice soft and general, and surgery hard but neither general nor specific. Thirdly, these attitudes tended to differ between preclinical and clinical students, but only modestly, in that some extreme (positive and negative) attitudes were modified by experience. PMID- 3101941 TI - Closely observed pains. PMID- 3101942 TI - The 100th birthday of appendicitis. PMID- 3101943 TI - Saint who's? PMID- 3101944 TI - Looking for Mozart ears. PMID- 3101946 TI - Enthusiasms: a tropical wreath for Liszt. PMID- 3101945 TI - Rachmaninov and Marfan's syndrome. PMID- 3101947 TI - Gustav Mahler and Emanuel Libman: bacterial endocarditis in 1911. PMID- 3101948 TI - Beauty and the dole. PMID- 3101949 TI - Early bent knee prostheses: ancestors of K9. PMID- 3101952 TI - Have jet, will fly. PMID- 3101950 TI - A new way of looking at Manet: the revelations of radiography. PMID- 3101951 TI - The fun and fear of flying. PMID- 3101953 TI - Death in the clouds. PMID- 3101954 TI - False negative tuberculin tests: check your Heaf gun. PMID- 3101955 TI - Fracture of humerus during use of an arm wrestling machine. PMID- 3101956 TI - Effect of scalp burns on common male pattern baldness. PMID- 3101957 TI - Wellie thrower's finger. PMID- 3101958 TI - Penetrating orbitocranial injury with a snooker cue. PMID- 3101959 TI - Outbreak of Weil's disease in a food fad commune in India. PMID- 3101960 TI - From exhaustion, exposure, and hunger to extreme voraciousness: bulimia. PMID- 3101961 TI - A "cracking" complication of hemiarthroplasty of the hip. PMID- 3101962 TI - Planting mangoes for the future in Tibet. PMID- 3101963 TI - Scott: 75 years on. PMID- 3101964 TI - Priests and polio: research in a warmhearted climate. PMID- 3101965 TI - Called as an expert witness. PMID- 3101966 TI - Insulin and independence. PMID- 3101967 TI - Life in the Lutyens household. PMID- 3101968 TI - From buying beds to upgrading an old rural hospital. PMID- 3101969 TI - Down on the health farm. PMID- 3101970 TI - Holding the mirror. PMID- 3101971 TI - What is a brain, and who said so? PMID- 3101972 TI - Three into five won't go. PMID- 3101973 TI - Effect of spinal norepinephrine depletion on descending inhibition of the tail flick reflex from the locus coeruleus and lateral reticular nucleus in the rat. AB - The lateral reticular nucleus (LRN) and locus coeruleus-subcoeruleus (LC/SC), brainstem structures which overlap the A1 and A6 noradrenergic nuclei respectively, have been implicated in descending modulation of spinal nociceptive transmission. The present studies were designed to examine the role of norepinephrine (NE) in the mediation of inhibition of the nociceptive tail flick reflex produced by focal electrical stimulation in the LRN and LC/SC. Spinal NE was depleted by intrathecal administration of 6-hydroxydopamine (6-OHDA; 20 micrograms) and the threshold electrical stimulation in the LRN and the LC/SC necessary to inhibit the tail flick reflex in lightly pentobarbital-anesthetized rats was determined 9 and 14 days later. Despite a significant depletion (greater than 85%) of lumbar spinal cord NE content, there was no significant change in the tail flick inhibitory stimulation thresholds in the LRN or LC/SC. NE depletion did, however, potentiate the elevation in the inhibitory stimulation threshold in the LRN produced by intrathecal administration of the alpha 2 adrenoceptor antagonist, yohimbine, suggesting that upregulation of spinal adrenoceptors had occurred following 6-OHDA treatment. Adrenoceptor up-regulation was examined quantitatively by characterizing the dose-dependent antinociceptive potency of the selective alpha 2-adrenoceptor agonist clonidine 3, 7, 10, and 14 days following 6-OHDA administration, and analysis of [3H]rauwolscine binding to lumbar spinal cord 9 days following administration of the neurotoxin. The development of supersensitivity, defined as the leftward parallel shift of the dose-response curves for clonidine administered intrathecally, corresponded to the time course of NE depletion following 6-OHDA treatment on the days tested. Binding of [3H]rauwolscine to lumbar spinal cord revealed an elevation in the estimated Bmax without a change in the estimated Kd of the high affinity binding component 9 days following 6-OHDA administration. This study demonstrates that spinal adrenoceptor denervation supersensitivity develops rapidly following intrathecal administration of 6-OHDA and compensates for the selective destruction of spinal noradrenergic nerve terminals. Thus, the absence of effect of NE depletion on the tail flick inhibitory stimulation threshold in the LRN and the LC/SC does not argue against the hypothesis that spinopetal NE-containing neurons in these brainstem loci are involved in modulation of spinal nociceptive transmission. PMID- 3101974 TI - Ictal and enduring interictal disturbances in emotional behaviour in an animal model of temporal lobe epilepsy. AB - Unilateral microinjections of kainic acid (4.7 nmol) were made into the dorsal hippocampus of 17 unanesthetized freely moving cats. These injections provoked an acute period of intense seizure activity (first 48-72 h) which in 10 cats was followed by a chronic period of recurrent spontaneous complex partial seizures persisting for as long as the cats were studied (up to 4 months). During the chronic epileptic period 8 of these 10 cats demonstrated both ictal and interictal emotional behaviour disturbances. The ictal events included behaviour similar to a 'defensive rage' reaction. Interictally, each of the cats demonstrated an emotional lability. That is, although they behaved in a normal manner if handled affectionately, any mild provocation triggered an explosive defensive rage reaction. As well, the thresholds for electrical brain stimulation induced defensive rage were lowered. That the interictal emotional behaviour disturbances were related to the presence of an active epileptogenic process was suggested by the finding that during periods when no spontaneous seizures were observed for several days, the cats reverted to a less emotionally reactive state and the thresholds for stimulation-induced defence reactions returned to baseline. The results indicate that epileptogenic lesions of the temporal lobe alone can induce an enduring disturbance of emotional behaviour. They support the view that emotional disturbances in patients with epilepsy may sometimes result from pathophysiological mechanisms related to the epileptogenic process, and further suggest that such emotional disturbances might be reversed or prevented if the epileptic seizures could be controlled. PMID- 3101975 TI - Morphology and distribution of the motor neurons of the accessory nerve (nXI) in the Japanese toad: a cobaltic lysine study. AB - Motoneurons supplying the accessory nerve (nXI) of the Japanese toad were retrogradely labelled by applying the cobaltic lysine to the cut end of the nerve. They had morphological characteristics and a distribution pattern similar to those of the rostral spinal motoneurons rather than the branchial motoneurons. We propose that the anuran nXI is equivalent to the so-called spinal portion of the nXI of other vertebrates, and both should be regarded as part of the rostral spinal nerves rather than the nerve accessory to the vagus nerve. PMID- 3101976 TI - Morphology and distribution of the preganglionic parasympathetic neurons of the facial, glossopharyngeal and vagus nerves in the Japanese toad: a cobaltic lysine study. AB - We labelled the preganglionic parasympathetic neurons of the facial, glossopharyngeal and vagus nerves of the Japanese toad by applying the cobaltic lysine to the cut end of the respective nerve, and examined their morphology and distribution. These neurons form an almost continuous cell column consisting of small neurons with less elaborate dendrites, and occupy a more dorsal position than the motoneurons of the corresponding nerves. The results suggest the presence of the amphibian homologues of the salivatory nucleus and the dorsal motor nucleus of the vagus. PMID- 3101977 TI - Mammillothalamic enkephalinergic pathway in the rat: an immunocytochemical analysis. AB - We studied the afferent sources of Leu-enkephalin (ENK) -like immunoreactive (ENKI) fibers in the anteroventral thalamic nucleus (AV) of the rat using experimental immunohistochemistry. These fibers were markedly fewer on the operated side after the destruction of the medial mammillary nucleus pars medialis where a number of ENKI cells were observed. This strongly suggests that these ENKI cells project ipsilaterally to the AV. ENKI fibers seemed to reach the AV via the mammillothalamic tract. PMID- 3101979 TI - Chronic administration of desipramine or nialamide decreases wet-dog shakes in rats produced by the TRH-analog MK-771. AB - The effect of chronic administration of the tricyclic antidepressant, desipramine, or the monoamine oxidase inhibitor (MAOI), nialamide, on the ability of the TRH analog, MK-771, to induce wet-dog shakes in rats was examined. MK-771 at a dose of 3 mg/kg produced significantly fewer wet-dog shakes in those animals treated repeatedly with either nialamide or DMI in comparison to those animals treated chronically with saline. Acute administration of these antidepressant compounds did not alter the ability of MK-771 to produce wet-dog shakes in rats. The results of these experiments indicate that TRH responsiveness in the CNS is reduced by chronic but not acute antidepressant drug treatment, and suggest that TRH may be involved in antidepressant drug action. PMID- 3101978 TI - Differential and asymmetrical behavioral effects of electrolytic or 6 hydroxydopamine lesions in the nucleus accumbens. AB - Sprague-Dawley rats received either unilateral or bilateral electrolytic or 6 hydroxydopamine (6-OHDA) lesions in the nucleus accumbens (n. acc.) and daily spontaneous activity was measured in home cage running wheels for 30 days postoperatively. Bilateral electrolytic lesions increased activity to 230% of preoperative baseline. Right electrolytic lesions produced a 50% increase in activity while left lesion rats were not significantly different from sham operated controls. Conversely, 6-OHDA lesions depressed activity. Bilateral 6 OHDA lesions had the greatest depressant effect upon activity while unilateral left or right n. acc. treatments produced relatively less hypoactivity. Results support an asymmetrically organized serial inhibition model of spontaneous locomotor control. PMID- 3101980 TI - Transient elevation of intrasynaptosomal free calcium by putrescine. AB - The role of polyamines in the regulation of free intrasynaptosomal Ca2+, [Ca2+]i was studied. After preincubation of rat brain synaptosomes with 5 mM difluormethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, the K+-induced increase of [Ca2+]i was 33% less than that in non treated synaptosomes. Putrescine (1 mM) added together with DFMO negated the effect of DFMO suggesting that abnormally low polyamine concentrations were the reason for the diminished K+-response. Putrescine alone did not alter the K+ response to [Ca2+]i. Instead putrescine (0.5 mM) caused a rapid (less than 10 s) transient increase in [Ca2+]i but did not simultaneously increase 45Ca2+ uptake into polarized synaptosomes. Neither spermidine nor spermine (0.5 mM) significantly altered [Ca2+]i. The results suggest that polyamines play a role in the regulation of free intrasynaptosomal Ca2+. PMID- 3101981 TI - Protein consumption increases tyrosine concentration and in vivo tyrosine hydroxylation rate in the light-adapted rat retina. AB - The ingestion of a single, 40% protein meal increased serum and retinal tyrosine levels and stimulated retinal tyrosine hydroxylation rate in light-adapted rats. Consumption of a similar, protein-free meal elicited none of these effects. The results thus indicate for retinal dopamine neurons that physiologically induced increases in tyrosine level can readily stimulate in vivo tyrosine hydroxylation rate. PMID- 3101982 TI - Effect of desmethylimipramine on norepinephrine content and plasticity of kitten visual cortex. AB - Because norepinephrine (NE) reuptake inhibitors have been reported to block 6 hydroxydopamine (6-OHDA) induced NE depletion, we wondered whether a reuptake inhibitor would block 6-OHDA's effects on visual cortical plasticity. We found, however, that desmethylimipramine (DMI) did not reduce 6-OHDA-induced NE depletion at 6-OHDA doses sufficient to prevent the effects of monocular deprivation. We also found that DMI itself induced transient NE depletion. We used this last result to further examine the NE hypothesis of depletion. In contrast to 6-OHDA-induced NE depletion, DMI-induced NE depletion was not accompanied by changes in visual cortical plasticity. PMID- 3101983 TI - [Expression of the hepatitis B virus surface antigen gene by rat hepatocyte X mouse hepatoma hybrid cells]. AB - The expression of the S gene of hepatitis B virus has been studied in the somatic hybrid cells resulting from the fusion between rat hepatocytes in primary culture and cells of the mouse hepatoma line BWTG3, and in the parental line BWTG3. The DNA of the S gene inserted into the plasmids pAC Tk+ and pNY4 has been co transfected into these cells with a plasmid DNA bearing a resistance gene to aminoglycoside. The level of expression of the S gene among the co-transfected resistant clones was estimated by radioimmunoassay. The results show that a high number of the co-transfected cellular hybrid clones express the S gene, whereas it is found, by contrast, that the S gene is poorly expressed in the mouse hepatoma cells. The level of expression of the S gene (as the amount of HBs Ag synthesized) is high in the hybrid clones and the synthesis of the HBs antigen is stable in time. These observations suggest for the first time in cell cultures in vitro, the role which is probably played by the normal hepatocyte genome in the expression of the S gene of HBV. PMID- 3101984 TI - [Synthesis of paf-acether by E. coli K12]. AB - Paf-acether (platelet-activating factor) is one of the most potent mediator of inflammation released from and acting on most cells that participate in inflammatory diseases. Its molecular structure is 1-O-alkyl-2-O-acetyl-sn-glycero 3-phosphocholine. Two metabolic steps are involved in its biosynthesis: the action of a phospholipase A2 on choline-containing membrane alkyl-ether lipids results in the production of lyso paf-acether and acetylation of the lyso compound by an acetyltransferase yields the biologically active molecule. Membrane alkyl-ether lipids can therefore be considered as potential precursors of paf-acether and their composition has been studied in various cell types. In this work, we investigated the presence of paf-acether in E. coli. Our results showed that paf-acether can be obtained from E. coli K12 under a variety of bacterial growth conditions. Paf-acether from E. coli exhibited the same physicochemical and biological characteristics as synthetic paf-acether and that from eucaryotic cells. Therefore, it appears that E. coli itself has the ability of producing paf-acether, a result that could be of some importance with respect to the pathogenesis of Enterobacteria and the use of E. coli in the recombinant DNA technology. PMID- 3101985 TI - [Anti-obesity activity of 3-hydroxymethyl N-methyl piperidine 4 chlorophenoxyacetate hydrochloride in mice treated with gold thioglucose]. AB - The 3-hydroxymethyl N-methyl piperidine 4-chlorophenoxyacetate, hydrochloride, A, a potent anorectic, reduces weight gain of gold thioglucose obese mice through a reduced body fat and a decrease in metabolic efficiency. Compound A has much less effect in the lean mice than in the obese models. In contrast with pair-fed obese or lean mice, the decreased food consumption cannot account for all the reduced weight gain of the obese controls. Basal lipolytic activity in parametrial adipose tissue is greater in obese mice treated with A then in controls. It seems that the stimulating effect of A on lipolysis could contribute to the weight reduction. PMID- 3101986 TI - [Tentative estimation of the total number of domestic cats in the world]. AB - Information on the size of populations of domestic cats from 42 countries allow us to estimate the total number of cats in the world: 400 millions. Methods and results are discussed. PMID- 3101987 TI - [Movement of Na+ and Cl- across the isolated fetal rat stomach]. AB - Unidirectional and net isotopic fluxes of Na+ and Cl- were determined at steady state across isolated stomach of rat fetuses on days 19 and 21. On day 19, when parietal cells are not yet functional, net absorptions of Na+ and Cl- (respectively: 3.8 +/- 1.1 and 5.2 +/- 1.7 mu eq X h-1 X cm-2) were observed. By contrast, active secretion of Cl- (-2.1 +/- 1.8 mu eq X h-1 X cm-2) associated with decreased absorption of Na+ (45%) was noted on day 21, and both Na+ and Cl- net movements accounted for the short-circuit current, as observed on adult gastric mucosa. These results show that Na+ active absorption precedes Cl- secretion in fetal rat at the time of parietal cells differenciation. PMID- 3101988 TI - [Relationship between base composition in non-coding DNA of genes and codon composition]. AB - The C + G percentage in third position of codons is linearly dependent on the C + G composition of flanking regions and introns. A similar relationship is shown for the first and second position which significantly influence the nature of amino acid sequence. If mutations would be oriented according to the local base composition, this will imply that genes of the same multigenic family would evolve at different rate. PMID- 3101989 TI - [Effects of acute or chronic administration of desmethylimipramine on the local level of methionine incorporation in cerebral proteins in freely moving rats]. AB - Incorporation of methionine into brain proteins has been measured by quantitative autoradiography after desmethylimipramine administration in rats. Acute treatment decreased protein synthesis in three regions: hippocampus, hypothalamus and habenula. After chronic treatment the decrease extended to four other regions: substantia nigra, raphe dorsalis, trigeminal nerve and hypophysis. An opposite effect was observed in the retrosplenial cortex. PMID- 3101991 TI - [Circumferential analysis of digitalized gamma angiocardiography by assessment of regional left ventricular contraction]. AB - After acquisition of a digital equilibrium gamma-angiocardiographie, circumferential analysis of end-diastolic and end-systolic frames gives 120 points diastolic and systolic curves. Their difference represents systolic volume and leads to regional left ventricular ejection fraction assessment at the considered radius level. The circumferential analysis evolute gives the regional left ventricular ejection fraction representative curves which allows especially differential diagnosis between left ventricular akinesia and dyskinesia. PMID- 3101992 TI - [Assignment, by proton magnetic resonance, of histidines of dihydrofolate reductase from chicken liver]. AB - The effects of pH and temperature upon C epsilon 1 H resonances of the four histidyl residues of chicken liver dihydrofolate reductase in binary complex with methotrexate were studied by 500-MHz 1H NMR spectroscopy. The four histidines labelled a, b, c, d are distinguishable by their pK values and the chemical shifts of their C epsilon 1H protons. The local electromagnetic environment as deduced from X-ray studies at 2.9 A resolution was used as a basis for proposed assignment of the four histidines. The assignments were a: H42, b: H140, c: H131, d: H87. Furthermore the histidyl residue labelled c was shown to be upfield shifted in its C epsilon 1H proton in the enzyme-methotrexate complex compared to the native enzyme. The hypothesis of a conformational change of the protein is discussed. PMID- 3101990 TI - [Cytoarchitectonic localization of foci of electrocortical activity accompanying focused attention in cats]. AB - Beta electrocorticographic rhythms (30-45 Hz) develop during focused immobile attention within two distinct foci in cats. A multiple electrode exploration was performed, followed by post-mortem histological analysis, to determine the precise localization of these foci. Electrode tips recording beta rhythms in the waking attentive cat were located: in motor areas (Brodmann's areas 4 and 6), in a band extending from the postcruciate cortex to the walls of the presylvian sulcus, crossing the frontal pole (anterior beta focus); in the posterior parietal associative area 5a, along the divisions of the ansate sulcus (posterior beta focus). The two foci are separated by somatic areas 3, 2 and 1, where beta rhythms were never recorded. The location of the posterior focus may suggest that area 5 is, in the cat as it is in the monkey, involved in motor control. PMID- 3101993 TI - [Demonstration of Cajal-Retzius cells and their processes in the neocortex of newborn mice using horseradish peroxidase]. AB - In newborn mouse neocortex, the so-called Cajal-Retzius cells (CRc), which are usually considered as neurons due to their polarity, located exclusively in the first cortical layer, were visualized using local application of horseradish peroxidase (HRP) on the neocortex followed by its tangential sectioning. Close to the application site, the exogenous enzyme, taken up by some of the CRc, was revealed with 3,3' diaminobenzidin (DAB) according to the Graham and Karnovsky technique. The brown reaction product was seen to fill almost completely some of these cells giving a "Golgi like" picture. They had a fusiform bipolar pericaryon and processes extending only into the first cortical layer. A single thick process whose length reached 300 to 400 microns, almost rectilinear and tapering progressively at its end was a dendrite which bore thin expansions reaching the cortical surface where they sometimes ramified between the endfeet of the radial glia. The dendrite sometimes showed symmetrical synapses with an afferent axon of unknown origin. The CRc axon was very thin (0.5 microns in diameter) and gave off at random numerous collaterals whose number and trajectories varied greatly from one cell to the other. The axonal processes could often be followed over a millimeter. They ended either abruptly because HRP had not diffused far enough into the process or terminated with large growth cones bearing numerous digitiform filopodia. The presence of growth cones thus suggested that the processes were exploring the cellular environment of the first cortical layer. In the newborn, CRcs appeared as still immature neurons. PMID- 3101994 TI - [A family of hypervariable minisatellites detected by means of a sequence derived from phage M 13]. AB - A new family of "hypervariable minisatellites" has been identified in the genome of man and of a variety of animal species using as a probe a DNA segment isolated from the M 13 bacteriophage. This finding provides a new series of hyperpolymorphic genetic markers and renders the "DNA-fingerprinting" methodology available to every molecular biology laboratory. PMID- 3101995 TI - [Labile behavior of gels and possible biological implications]. AB - Gelated networks of biopolymers submitted to thermal cycles may undergo phase transitions and phase-separations, and their cryobehavior is chiefly associated with such phenomena. The properties unveiled with models on a macroscopic scale may have implications in the cryobehavior of living systems while the lability of biopolymer gels under the influence of other external conditions may be involved in a number of biological functions. PMID- 3101996 TI - [Alpha genes of the T cell receptor: a possible implication in genetic susceptibility to multiple sclerosis]. AB - Multiple sclerosis (MS) is a neurological disease in which 60% of patients are DR2 (versus 20% in controls). Restriction fragment length polymorphism (RFLP) associated with T cell receptor alpha-chain and beta-chain genes have been analysed in a sample of 46 MS patients and compared with those of 142 controls. The alpha-chain gene polymorphism is localized to the V-J region and consists of 3 Bgl II alleles (alpha a = 3.2 kb; alpha b = 2.9 kb; alpha c = 2.8 kb). A significant difference was found in the distribution of these three alleles since 97% of DR2 patients versus 60% in DR2 non-MS individuals were found to be homozygotes alpha a/alpha a. These results suggest the influence of T cell antigen receptor germ line repertoire on the etiopathology of this disease. PMID- 3101997 TI - [Metastases of human tumor cells in immunosuppressed newborn rats]. AB - The metastatic ability of human tumour cells can easily be evaluated by using as an experimental model the production of metastases in newborn rats immunosuppressed by an optimal dose of anti-thymocyte serum. Thus, following sub cutaneous injection of 10(6) cells, a human melanoma cell line, tumorigenic but non metastatic in nude mice, produces within 3 weeks tumours in all inoculated rats and lymph node and pulmonary metastases in 50% of the animals. The cloning of this cell line in semi-solid agar shows its heterogeneity and demonstrates that it contains poorly tumorigenic but highly metastatic cells. PMID- 3101998 TI - [Histo-immunolocalization of human and murine type I and III collagens in human cancers grafted to congenital athymic mice]. AB - Seven human carcinomas and five sarcomas are microsurgically grafted to the nude mouse. We demonstrate with antibodies to human and murin Type I and III collagens that the capsule of the grafted human tumors and the intratumoral perivascular collagen are always of murin origin. Mouse Type I and III collagens take progressively the place of their human counterparts in the extracellular matrix of carcinoma. In contrast the intratumoral collagens of sarcomas are ever of human nature. The murin collagen, probably induced by the tumors, is perhaps one of the factors which prevents in the nude mouse the metastasis of the human grafted tumors. PMID- 3101999 TI - [Effects of adrenalectomy on in vitro evoked electrophysiological activity of the hippocampus in BALB/c mice]. AB - The physiological properties of hippocampal slices from intact or adrenalectomized (ADX) BALB/c mice were studied in vitro. Mouse hippocampal slices displayed features similar to those observed in other species in terms of postsynaptic characteristics of response to stratum radiatum stimulation. In adrenalectomized mouse, the amplitude of population spike was reduced whereas the latency of population spike and cell responses to paired stimuli volleys were unchanged. The role of the endocrine status in this modification is discussed. PMID- 3102000 TI - [Influence of purified cellulose level in the diet of pigs on intestinal absorption of volatile fatty acids]. AB - Nutrient and volatile fatty acid (VFA) absorption to portal blood was measured twice at 7 days interval in five pigs fed a semi-synthetic diet containing 6 (R6) or 16% (R16) purified cellulose for 21 or 7 days. The daily absorption (24 hrs.) of VFA in the large intestine which was larger (NS) when the cellulose level rose, increased significantly (P less than 0.05) with increasing length of adaptation (21 to 28 d.) to the diet whatever the cellulose level. The supplementary daily supply of energy in the form of VFA after increase of the cellulose level did not compensate for the corresponding deficit of absorption of reducing sugars and crude protein in the small intestine. PMID- 3102001 TI - [Immunocytochemical study at the ultrastructural level of neurofibrillary degeneration in Alzheimer's disease]. AB - Paired Helical Filaments (PHF), as demonstrated at the ultrastructure level, are one of the main pathological landmarks of Alzheimer's disease (AD). A polyclonal rabbit antiserum raised against PHF had been shown to label tangles and the periphery of plaques at the light microscope level. The same antiserum labels PHF specifically at the ultrastructure level, as demonstrated with a postembedding immunogold technique. Normal cytoskeleton constituents and plaque amyloid were not labelled. Specific labelling of a characteristic landmark may be a clue for a biological marker of AD. PMID- 3102002 TI - Coping with problems related to cancer and cancer treatment. PMID- 3102003 TI - Questionable cancer treatments. PMID- 3102004 TI - Benign soft tissue tumors: classification and natural history. PMID- 3102005 TI - Cancer of the ear. PMID- 3102006 TI - The role of the tumor board in a community hospital. AB - A hospital tumor board is a multidisciplinary group of physicians that meets on a regular basis to review cancer cases. Through regular meetings, the tumor board will improve the quality of cancer care, provide educational opportunities for participants, and become an asset to the hospital and to the community. The use of multidisciplinary tumor-board consultations can ensure that the cancer patient has access to the best current thinking about cancer management. This structure provides the individual practitioner and his hospital with the educational, quality assurance, and legal mechanisms to deliver state-of-the-art care. PMID- 3102007 TI - Cancer chemotherapeutic agents. PMID- 3102008 TI - [Lymphocytic and hepatocytic changes in chronic hepatitis B and their bearing on viral replication]. PMID- 3102009 TI - [Epidemiologic analysis of cerebral apoplexy in a population of 700,000 in Beijing]. PMID- 3102010 TI - [Experimental study on the killing effect of hyperbaric oxygen combined with photodynamic therapy on transplanted tumors in mice]. PMID- 3102011 TI - [Effect of local PUVA on epidermal Langerhans' cells in guinea pigs]. PMID- 3102012 TI - [Effect of fasting and rapid exercise with a sliding board on the metabolism of diabetics]. PMID- 3102013 TI - [Patho-anatomical analysis of the cause of death in 9,818 neonates]. PMID- 3102014 TI - [Positive false reaction of HBsAg (by RPHA) in patients with schistosomiasis and its mechanism]. PMID- 3102015 TI - [Effect of urinary kinin on the excretion of water and electrolytes and the regulation of blood pressure in normal adults]. PMID- 3102016 TI - [Effect of albendazole in the treatment of nematodiasis, cestodiasis and protozoiasis]. PMID- 3102017 TI - Osteoporosis: a big challenge to public health. PMID- 3102018 TI - Calcitonin secretion in streak gonad syndrome (Turner's syndrome). AB - Osteoporosis in one of the most common complications of streak gonad syndrome (SGS), however, its pathogenesis is still unclear. To test whether SGS is associated with calcitonin (CT) deficiency, 11 affected individuals and 8 age matched healthy women were studied. Calcium, 3.6 mg/kg b.w. as a 10% solution of calcium chloride, was given intravenously for 3 minutes. Serum levels of CT and calcium were measured before and at 5, 30, 60, and 120 minutes after the injection. There was a statistically significant rise in serum calcium levels both in the control subjects and patients with SGS, with significantly lower levels prior to and at 30, 60, and 120 minutes following calcium load in the control group. The CT rise following calcium load was also significant at 5, 30, and 60 minutes in the controls and at 5 and 30 minutes in patients with SGS, with a significantly lower baseline and 30, 60, and 120 minutes levels in the latter group. Maximum levels of calcium and CT occurred 5 minutes after the calcium load and were statistically indistinguishable. There were no significant differences in either the calcium or the CT incremental changes between the two groups. These findings are consistent with decreased basal (and 30-120 minute) CT levels in SGS and suggest that CT deficiency may be involved in the development of osteoporosis in patients with SGS. The possible causal relationship of estrogen deficiency to the reduced CT levels in SGS is discussed. PMID- 3102019 TI - Absence of evidence for a role of calcitonin in the etiology of femoral neck fracture. AB - Twenty elderly women with fracture of the femoral neck were compared with 10 age matched women undergoing elective hip surgery. In spite of an equivalent calcium response to intravenous calcium, neither basal nor stimulated calcitonin levels were significantly different between the groups. Parathormone, 25OHD, and 1,25(OHD)2 showed no significant differences between the femoral neck fracture group and control subjects. It is thus unlikely that calcitonin has an important role in the etiology of postmenopausal osteoporosis associated with femoral neck fracture. PMID- 3102020 TI - Radioimmunoassay for human osteocalcin using an antibody raised against the synthetic human (h37-49) sequence. AB - Radioiodination of synthetic human 37-49 osteocalcin requires optimal labeling conditions in order to obtain a maximum of mono- and di-iodinated tracer with little contamination by tri- and tetra-iodinated products or "radio-damage." The antibody raised against osteocalcin(h37-49) had the highest affinity for the C terminal peptide used for iodination and the larger peptide (h30-49). The intact bovine osteocalcin (b1-49) revealed less immunoreactivity. This C-terminal specific radioimmunoassay detected the intact human osteocalcin in HPLC purified plasma and peritoneal dialysate from patients with terminal renal insufficiency and in extracted human bone. Some quantities of osteocalcin peptides with a higher hydrophobicity were predominantly detected in uremic plasma. These peptides that had a higher molecular weight than the intact human molecule might represent aggregated forms of the intact bone-derived osteocalcin. Immunoreactivity in plasma samples from healthy individuals revealed a remarkable difference as to which substance was employed for anticoagulation. Compared to heparin, the addition of EDTA largely reduced the osteocalcin immunoreactivity, implying that conformational changes within the N-terminal portion (containing the Gla- and Cys-residues) are extended to the C-terminal portion. PMID- 3102021 TI - Plasma calcium and phosphate levels in an adult noninsulin-dependent diabetic population. AB - Duplicate or triplicate measurements of fasting plasma glucose, calcium (Ca), phosphate (Pi), and glycosylated hemoglobins were performed on a group of non insulin dependent diabetic patients and controls at 3-6 month intervals. In the diabetic group (48 males and 44 females), 18 were on diet only, 21 on diet and oral hypoglycemic treatment, and 51 on diet and insulin. These were a total of 217 measurements for each parameter. Results were compared to 416 measurements obtained from sex and age-matched controls. Plasma Ca levels were higher in the diabetic group (2.48 +/- 0.004 vs 2.38 +/- 0.006 mmol/liter) P less than 0.001; plasma Pi levels were similar to those of controls. The difference in plasma Ca was not influenced by age, sex, or mode of treatment. No correlation was found in the three treatment groups between plasma Ca and duration of diabetes nor with patients' weights. The results are consistent with the view that an alteration in calcium homeostasis accompanies the diabetic state. PMID- 3102022 TI - Inhibition of in vitro mineralization by aluminum in a clonal osteoblastlike cell line, MC3T3-E1. AB - The direct effect of aluminum on mineralization was examined using an osteoblastlike cell line, MC3T3-E1. The mineralization process was quantitated by measuring 45Ca accumulation into the cell and matrix layer of MC3T3-E1 cells in culture. The accumulation of 45Ca into the cell and matrix layer increased dramatically after 13 days of culture without a parallel change in the DNA content of these cells. Because nodular clusters of cells appear around the same period in which a massive mineralization occurs, the marked increase in 45Ca accumulation after the 13th day of culture appears to represent deposition of 45Ca into the extracellular matrix. Thus, this culture system offers a useful model for making a quantitative estimation of osteoblast-mediated mineralization in vitro. When aluminum was added to this system, the accumulation of 45Ca into the cell matrix layer was inhibited in a dose-dependent manner: 10(-6) M aluminum reduced 45Ca accumulation to 40.8 +/- 2.7% of that in nontreated cells without affecting alkaline phosphatase activity or the DNA content of these cells. Because the concentration of aluminum used in this study is well within the range of serum aluminum levels seen in chronic dialysis patients, the direct effects of aluminum on osteoblast-mediated mineralization shown in the present study may underlie the development of so-called aluminum-induced "osteomalacia" in certain dialysis patients. PMID- 3102023 TI - 25-Hydroxyvitamin D3 metabolism in a human leukemia cell line. AB - 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a potent inducer of monocytic differentiation of the human promyelocytic leukemia cell line, HL-60. We have noted that 25-hydroxyvitamin D3 (25(OH)D3) in high doses is also capable of promoting monocytic differentiation of this cell line. To test the possibility that the latter activity is due to conversion of 25OHD3 to 1,25(OH)2D3 by HL-60, we exposed HL-60 cells to 25OHD3 and analyzed the products by HPLC and radioreceptor assay. When chromatographed in the traditional solvent system (isopropanol-hexane), a new peak appears which migrates with authentic 1,25(OH)2D3. However, in a solvent system containing dichloromethane, 90% of the peak migrates with another metabolite, 19-Nor-10-Keto-25OHD3 (19-Nor-25OHD3). Production of this metabolite is enhanced by living cells and is synthesized by both virgin HL-60 and those which have undergone differentiation. We next determined if authentic 19-Nor-25OHD3 also promotes differentiation of this cell. As assessed by appearance of the monocyte-specific surface antigen (63D3) and macrophage-specific esterase activity, we find that this metabolite does, in fact, induce monocytic differentiation of HL-60 with a potency of approximately 1/200 that of 1,25(OH)2D3 and similar to that of 25OHD3. In agreement with the effect upon cell maturation, 19-Nor-25OHD3 displaces 3H-1,25(OH)2D3 from its HL 60 receptor with an efficiency comparable to 25OHD3. Hence, HL-60 cells convert 25OHD3 to 19-Nor-25OHD3, and 19-Nor-25OHD3 induces monocytic differentiation of HL-60 with comparable efficiency to its precursor, 25OHD3. PMID- 3102024 TI - In vitro bone resorption activity produced by a hypercalcemic adenocarcinoma tumor line (CAC-8) in nude mice. AB - Tumor extracts and conditioned tissue culture media from a canine adenocarcinoma tumor line (CAC-8) propagated in nude mice significantly increased in vitro bone resorption in neonatal mouse calvaria as measured by release of previously incorporated 45Ca. In vitro bone resorption activity was induced in a dose dependent manner, was not suppressible by indomethacin, and was heat- and acid stable. Gel exclusion chromatography demonstrated peak bone resorbing activity at a relative molecular mass of approximately 28,000. The parathyroid hormone (PTH) antagonist (8,18norleucine, 34tyrosine) bovine PTH (3-34) amide did not inhibit CAC 8-stimulated or (1-34) bPTH-induced bone resorption. There was an increased number of tartrate-resistant, acid phosphatase-positive cells in calvariae exposed to CAC-8 extract. Ultrastructural evaluation of calvaria revealed hypertrophy and maturation of osteoclasts in calvaria exposed to CAC-8 extract. The maturation effects included close contact to bone surfaces and the presence of clear zones and ruffled borders in osteoclasts. Similar structures were observed infrequently in osteoclasts of control calvaria. These data demonstrate that the tumor line (CAC-8) contained activity capable of stimulating in vitro bone resorption by increasing osteoclast numbers and the activity of existing osteoclasts. PMID- 3102026 TI - Magnesium in tooth enamel and synthetic apatites. AB - The literature on how Mg is present in tooth enamel and on the incorporation of Mg in synthetic apatites is reviewed. Then a theoretical consideration is given on the basis of ionic radii about the incorporation of Mg in F-, Cl- and OH apatite. Finally, the results are given of experiments on the incorporation of Mg in fluor, chlor, hydroxy, and carbonate apatite. It appears that the extent of incorporation of Mg in the apatite lattice, if at all, is very limited and that Mg in tooth enamel is to a very limited extent incorporated in the apatite lattice, the main portion being surface bound or present in a separate phase. PMID- 3102025 TI - Pancreatic calculi containing brushite: ultrastructure and pathogenesis. AB - Six pancreatic calculi were analyzed by X-ray powder diffraction and scanning electron microscopy. All were found to contain calcite; however, small amounts of two other morphologically distinct deposits containing only Ca were also detected in some of the stones. It is suggested that these substances may be vaterite and aragonite. In addition, significant deposits of brushite, CaHPO4 X 2H2O, were identified on the outer surfaces of three of the stones. This substance has not been previously reported as a constituent of pancreatic calculi, and its presence is surprising since physico-chemical factors such as phosphate concentration and fluid pH do not favor its deposition. We suggest that precipitation of calcite in the pancreatic duct occurs as the primary event in the formation of pancreatic calculi and that it may continue until the duct is completely occluded. Thereafter, further growth causes injury to the duct wall resulting in the calcite core being exposed to phosphate in the tissue fluid. Deposition of brushite follows. PMID- 3102027 TI - Trifluorothymidine and 5-fluorouracil: antiproliferative activity in tissue culture. AB - The antiproliferative activity of trifluorothymidine (F3TDR) and 5-fluorouracil (5-FU), two cell-cycle-phase-specific antimetabolites, was compared in a tissue culture model of human scleral fibroblasts and rabbit corneal epithelial cells. The mean concentrations required to inhibit human scleral fibroblast proliferation to 50% of the control rate (ID50) after 5 days of exposure were 8.50 micrograms/mL for F3TDR and 0.43 microgram/mL for 5-FU. The corresponding ID50 levels for rabbit corneal epithelial cells were 0.24 microgram/mL and 0.42 microgram/mL. The ID50 of F3TDR was significantly higher than that of 5-FU in human scleral fibroblasts (p less than 0.001) but not in rabbit corneal epithelial cells. F3TDR appears to have no clinical advantage over 5-FU in minimizing corneal epithelial toxicity when given to prevent fibroblast proliferation after glaucoma filtering surgery. PMID- 3102028 TI - An estimate of the extent of deamination of L-serine in auxotrophs of Escherichia coli K-12. AB - We have shown that serine-glycine auxotrophs of Escherichia coli K-12 use exogenous L-serine inefficiently as a source of biosynthetic intermediates. Much of the L-serine supplied in the medium is not used to satisfy the auxotrophic requirement, owing to its diversion by L-serine deaminase, presumably to pyruvate. This is the first proof that the activity known as L-serine deaminase actually deaminates L-serine in vivo. PMID- 3102029 TI - Bactericidal action of carbon dioxide laser radiation in experimental dental root canals. AB - The ability of a carbon dioxide laser to sterilize the root canal of human teeth has been investigated. Three oral bacteria, Streptococcus sanguis, Streptococcus mutans, and Actinomyces viscosus, and three other bacteria, Bacillus cereus, Staphylococcus aureus, and Pseudomonas aeruginosa were used as experimental organisms. Exposure of cells on glass slides to laser radiation showed there was little difference in the exposure required to kill these six organisms. Complete recovery of bacteria from the root canal was initially a problem and was only achieved when bacterial manipulations and removal were carried out in rapid succession, within 5 min of inoculation. However, the geometry of the instrumented canal and the laser alignment were major factors in achieving consistent cell death of oral bacteria in the root canals. Using sets of 10 teeth, four repeated exposures of 10 W for 1 s was found to sterilize 4 or more of the teeth. PMID- 3102030 TI - Bacillus cereus endophthalmitis. AB - The authors present a case of a young man with post-traumatic endophthalmitis caused by Bacillus cereus. The clinical course was typical of the panophthalmitis caused by this toxin-producing organism: rapid onset of signs of systemic infection, a corneal ring abscess and eventual loss of the globe requiring enucleation. Studies of experimental rabbit models of the infection have indicated that the most efficacious regimen consists of systemic and topical clindamycin and gentamicin. Successful therapy depends upon immediate systemic administration of these agents when the clinical setting suggests Bacillus cereus infection. PMID- 3102031 TI - Sandoz: Swiss corporation moving towards global image. PMID- 3102032 TI - Anorexia nervosa. PMID- 3102034 TI - Therapeutic concepts of brachytherapy/megavoltage in sequence for pharyngeal wall cancers. Results of integrated dose therapy. AB - This is a follow-up report on lateral, posterior oro-, hypopharyngeal wall cancer treatment based on a new therapeutic concept. Ir-192 or I-125 brachytherapy and craniocervical megavoltage irradiation are effective with improved local control and NED (no evidence of disease) survival rates. Local failure rate is 14% and actuarial survival (NED) is 82% at 5 years in 14 patients treated thus far. PMID- 3102035 TI - Solitary plasmacytomas of bone and extramedullary plasmacytomas. A clinicopathologic and immunohistochemical study. AB - Twenty-two patients with solitary plasmacytoma of bone (SPB) and 13 with extramedullary plasmacytomas (EMP) were studied. The average follow-up period for SPB was 90 months and 86 months for EMP. Thirty-six percent of patients with SPB developed multiple myeloma (MM) in an average of 39 months, and 23% of patients with EMP developed MM in an average of 23 months. No significant differences in survival, incidence of MM, or interval to the development of MM were found between the two groups. The 11 cases of EMP with evaluable tissue for immunohistochemical study were either monotypic kappa or lambda, as were 9 of 10 SPB. Presence of monoclonality did not predict the development of MM. The histologic parameters of nuclear immaturity and presence of prominent nucleoli seem to be the best indicators of which patients will develop MM. Solitary plasmacytoma of bone and EMP appear to be more closely related than has been previously recognized. PMID- 3102033 TI - Undifferentiated leukemia of infancy with t(11:17) chromosomal rearrangement. Coexpressing myeloid and B cell restricted antigens. AB - It has been suggested that the malignant transformation, in some of the acute leukemias, may involve totipotent stem cells resulting in a biphenotypic leukemia expressing both myeloid, and lymphoid characteristics. We describe here a hybrid cell acute leukemia, in a 16-day-old infant, in whom leukemic cells coexpressed myeloid and lymphoid B cell antigens. Blast cells in the bone marrow showed L2 morphology according to the French American British (FAB) classification, with positive periodic-acid Schiff, and nonspecific esterase staining. Sudan black, and specific esterase were negative. Terminal deoxynucleotidyl transferase, was strongly positive in 5% of blasts, and faintly reactive with the rest. Karyotypic analysis demonstrated a translocation of t(11:17);(q23;p13). Immunoglobulin gene analysis revealed rearrangement of the heavy chain genes. The blasts' phenotype was HLA/DR+ B4+ My7+ My9+ common acute lymphoblastic leukemia antigen (CALLA) B1- T11-. Dual immunofluorescence staining using anti My7, and My9 fluorescein isothiocyanate, and anti B4 pycoerythrin conjugated monoclonal antibodies, and flow cytofluorometry, revealed a labeling pattern of 25% B4+; 10% to 15% My7+; 17% My9+; and 50% of cells coexpressing B4 My7, and My9 antigens. These results provide evidence for a hybrid leukemia with lymphomyeloblasts being part of a single clone, which may indicate the origin of this leukemic clone from a pluripotent (lymphoid/myeloid) stem cell. PMID- 3102036 TI - Body composition changes in marrow transplant recipients receiving total parenteral nutrition. AB - Nine patients with acute lymphocytic leukemia in remission, aged 12-35 years, undergoing allogeneic bone marrow transplantation (BMT) were studied for changes in body fluid balance and body composition. Body composition and fluids were assessed the first 4 weeks following BMT, using isotope dilution and anthropometry. Oral and parenteral nutrient intakes were recorded daily. Tracer dilution techniques were used to assess body fluid volumes and estimate body cell, lean body, and body fat masses. Body cell mass was lost (mean -1.62 kg, P less than 0.05) without significant changes in body fat or lean body masses. There was an expansion of the extracellular fluid compartment (mean +0.8 l, P less than 0.05) and a loss in the intracellular fluid compartment (mean -1.3 l, P less than 0.05) with little change in total body water volume. Changes in body weight correlated poorly with body cell mass or fluid volume changes. Change in arm muscle area correlated well with changes in body cell mass (r = 0.61, P less than 0.05) and lean body mass (r = 0.68, P less than 0.05), while that of arm fat area did not reflect its isotope dilution-derived counterpart. Instead, the change in arm fat area was related to shifts in fluid compartments. Prealbumin decreased significantly (mean -9.3 mg/dl, P less than 0.05), while albumin decreased slightly (mean -0.1 mg/dl), and both were related to changes in body cell mass. Nitrogen balance was negative throughout the study and the overall mean was related to the change in body cell mass (r = 0.60, P less than 0.05). Calorie and protein intakes were not associated with the changes in body composition, implying other causal factors. PMID- 3102037 TI - Galactosyltransferase: multiple forms in serum of normal and hepatoma Mc-29 bearing chickens and from liver and hepatoma microsomal and plasma membrane preparations. AB - The multiple forms of galactosyltransferase in chicken serum and in microsomal and plasma membrane preparations from liver and viral induced hepatoma Mc-29 have been studied by isoelectric focussing. An elevation of the hepatoma plasma membrane enzyme activity was described and in the pattern of the multiple forms of the enzyme two forms were found (pI-5.34 and 8.22) which were similar to those described in the serum of hepatoma bearing chickens (pI-5.36 and 8.24). A conclusion is drawn that these enzyme forms are apparently present to a greater extent in the hepatoma plasma membrane enriched fractions than in liver membranes and are probably shed into the serum of the tumor bearing animals. PMID- 3102038 TI - Effects of antioxidants on aflatoxin-induced hepatic tumors in rats. AB - Female Wistar rats pretreated with Aflatoxin B1 (AFB) were administered reduced glutathione, butylated hydroxytoluene, methionine or ascorbic acid on a daily basis, p.o., for 8 months. None of the treatments produced a decrease in incidence or size of hepatic nodules. While there was some evidence that ascorbic acid reduced the incidence of cystic cholangioma, the ascorbic acid and methionine treatment groups also contained significantly fewer animals surviving to the 26-month sacrifice. The lack of effect of glutathione is not consistent with previous work showing a marked glutathione dependent regression of AFB induced hepatocellular carcinoma. PMID- 3102039 TI - Metabolism of arylhydrazines by cytochrome P-450 mixed function oxidases and prostaglandin(H)synthase from mouse lungs. AB - The arylhydrazines 4-methylphenylhydrazine hydrochloride, N'-acetyl-4 methylphenylhydrazine and N'-acetyl-4-hydroxymethylphenylhydrazine (HMPH) were metabolized by ram seminal vesicle prostaglandin(H)synthase (P(H)S) and by cytochrome P-450- and P(H)S-dependent enzymes from mouse lung. Based on the Km values, the cytochrome P-450 enzymes were the most efficient, suggesting that they would be responsible for the metabolic activation of these compounds in vivo. Cytochrome P-450-dependent metabolism was inhibited by metyrapone and SKF 525A, ruling out the involvement of flavin mono-oxygenase. Agaritine, an arylhydrazide, was poorly metabolized by both systems. PMID- 3102040 TI - Diamineoxidase activity and tissue histamine content of human skin, breast and rectal carcinoma. AB - In view of the controversy that exists regarding the histamine content and diamine oxidase activity in relation to human carcinomatous growths, the present investigation was undertaken and carcinomatous tissues of skin, breast and rectum were analysed. The result of the experiment gives a clear evidence that both histamine concentration and diamine-oxidase activity increase significantly in all the three types of growth. The result has been discussed and a reasonable explanation has been offered for the observations made. PMID- 3102041 TI - Action of vitamin A on DNA adduct formation by aflatoxin B1 in a microsome catalyzed reaction. AB - The effect of vitamin A and some derivatives has been studied on the formation of DNA adduct by aflatoxin B1 (AFB1) in an in vitro reaction catalyzed by rat liver microsomes. Retinol, retinal, all trans retinoic acid and two retinyl esters were found to inhibit the adduct formation in a dose-dependent manner. The inhibition by retinol showed that it was prompt and could be reversed by increasing microsome concentration. Retinol also inhibited the formation of AFB1 adduct with microsomal protein. The inhibition of adduct formation with both DNA and protein was still apparent when repurified microsomes were used after pretreatment with retinol. Retinol inhibited adduct formation by virtue of its ability to interact with microsomal enzyme component(s), thereby interfering with the bioactivation of AFB1. The data are suggestive of a potential anticarcinogenic role for vitamin A against AFB1. PMID- 3102042 TI - Evaluation of premalignant and malignant lesions during the induction of mouse melanomas. AB - The objective of the present study was to evaluate the malignant and premalignant lesions that arise in C57BL/6 mice after treatment with 7,12 dimethylbenz(a)anthracene and croton oil. Tissues from 70 treated mice were evaluated by histological and transplantation techniques, and 17 (24%) were found to have malignant tumors. Eleven of the tumors were diagnosed as malignant melanomas, three as spindle cell sarcomas, and three as squamous cell carcinomas. The incidence of malignant melanomas (15.7%) in this group of mice was similar to that in our initial study on the induction of melanomas with 7,12-dimethylbenz(a) anthracene and croton oil, in which two of 20 mice developed malignant melanomas. Mice that developed melanomas had been treated with croton oil for an average of 7 mo, and the mean latent period for tumor development was 11 mo. Seven of eight melanomas grew rapidly after transplantation to syngeneic C57BL/6 mice. Pigmented nevi and/or draining lymph nodes from nine of 11 mice with melanomas grew progressively after transplantation to athymic nude mice. Pooled nevi from one mouse with no apparent tumors grew into a histologically malignant melanoma after transplantation to a nude mouse. Nevi from three mice with sarcomas, one mouse with a carcinoma, and 42 tumor-free treated mice failed to grow in nude transplant recipients. Thus, only nevi from mice with either apparent or occult malignant melanomas exhibited progressive growth in nude mice. These results confirm that malignant melanomas can be induced in C57BL/6 mice at a regular, predictable rate and further indicate that this is an excellent system in which to study melanoma induction, progression, and therapy. PMID- 3102043 TI - Hyperthermic enhancement of cell killing by mitomycin C in mitomycin C-resistant Chinese hamster ovary cells. AB - The interaction of hyperthermia and mitomycin C (MMC) was studied in wild-type Chinese hamster ovary cells and in Chinese hamster ovary cells selected for resistance to MMC. Hyperthermic potentiation of MMC activity was maximal if heating was done simultaneously, or up to 3 h following MMC exposure. Heat enhanced the effect of MMC in both drug-sensitive and -resistant cells. Dose enhancement ratios increased from 1.3-2.0 at 42 degrees C to 2.6-3.8 at 43.5 degrees C and were similar for all cell lines. Cellular uptake of MMC was determined by high pressure liquid chromatography. MMC uptake was similar in the drug-sensitive and -resistant cell lines at 37 degrees C. Hyperthermia (43.5 degrees C) increased cellular uptake of MMC by 78 and 27% in MMC-sensitive and resistant cell lines. MMC-resistant cells were more sensitive to heat alone at 42, 43, and 44 degrees C. The results suggest that tumor cells that have developed resistance to MMC might be treated effectively with MMC combined with heat to augment the response to MMC. Resistance to MMC may also render tumor cells more sensitive to hyperthermia. PMID- 3102044 TI - Time dependence for the protective effect of androgen from procarbazine-induced damage to rat spermatogenesis. AB - The protective effects of androgen pretreatment on the procarbazine-induced killing of spermatogonial stem cells in Wistar rats have been investigated. Using testosterone-filled Silastic implants (200 mm2) the degree of protection from four weekly doses of procarbazine (100 mg/kg) was found to be dependent upon the androgen pretreatment time interval as assessed by quantitative histology. No protective effect was seen until rats had received 4 wk of pretreatment with androgen, whereafter protection increased to a maximum (about 20 to 30% of tubule cross-sections exhibiting recovery) after 8 to 12 wk of pretreatment. In contrast, the same level of maximal protection could be obtained by 6 wk of pretreatment using testosterone enanthate, suggesting that differences in protection may be achieved using different modes of androgen administration. PMID- 3102045 TI - Effects of estradiol and tamoxifen on creatine kinase in rodent mammary carcinomas. AB - The effects of altered estrogenic environments on creatine kinase (CK) and adenylate kinase (AK) were studied in two rodent mammary tumor systems, R3230AC and primary 7,12-dimethylbenz(a)anthracene (DMBA)-induced carcinomas, to determine whether response of these enzymes could be related to their hormone dependence. The hormonal perturbations studied were ovariectomy and administration of various doses of estradiol valerate or the antiestrogen tamoxifen. Total CK activity and AK activity were assessed by a spectrophotometric assay followed by electrophoretic separation of the CK isozymes to determine their relative activities. In the ovarian-independent R3230AC tumors, estrogen treatment produced a dose-related decrease in CK activity, whereas CK was not responsive in ovarian-dependent DMBA-induced tumors. Adenylate kinase activity remained unchanged regardless of the hormonal perturbation. Glucose-6-phosphate dehydrogenase and lactate dehydrogenase, which were studied for comparative purposes, were both estrogen responsive. While both estrogenic and antiestrogenic effects on enzyme activities were observed in the DMBA-induced tumors, the effect of tamoxifen in the R3230AC tumors was generally estrogenic. We conclude that the effect of estrogen on CK-BB in DMBA-induced tumors is not sufficient to be used as a biochemical marker of hormone dependence. PMID- 3102046 TI - In vitro differentiation of T-cells capable of mediating the regression of established syngeneic tumors in mice. AB - Previous studies have shown that successful adoptive immunotherapy of a newly induced, weakly immunogenic murine sarcoma, MCA 105, can be achieved either with fresh noncultured immune spleen cells or with immune cells after in vitro stimulation and expansion. In this study, we utilized in vivo and in vitro depletions with monoclonal antibodies (mAb) of T-cell subpopulations expressing the L3T4 or Lyt-2 antigens to investigate the phenotype of the T-cells that mediate in vivo tumor regression. The efficiency of depletion was assessed by flow microfluorometric analysis and by the ability of specifically treated spleen cell populations to generate allogeneic cytotoxic T-lymphocytes. The therapeutic efficacy of adoptively transferred fresh noncultured MCA 105 immune cells was abrogated by in vivo administration of either L3T4 or Lyt-2 mAb to mice bearing 3 day established pulmonary metastases. In vitro treatment of fresh noncultured MCA 105 immune cells with either L3T4 or Lyt-2 mAb and complement also abrogated their antitumor efficacy confirming the initial findings. However, mixing L3T4 and Lyt-2 mAb and complement-treated MCA 105 immune cells reconstituted the antitumor efficacy indicating that cellular cooperation between these two lymphoid subpopulations was essential for the regression of established tumors. Unlike fresh noncultured immune cells, the antitumor efficacy of in vitro sensitized and expanded immune cells was abrogated by in vivo treatment with Lyt 2 but not with L3T4 mAb indicating Lyt-2+ cells alone played a major role in mediating the regression of tumors. These findings provide evidence for an in vitro-induced differentiation of therapeutic T-lymphocytes. Our results thus suggest that the antitumor activities expressed by the two types of cells may represent T-cells at different stages of immunological differentiation. PMID- 3102047 TI - Influence of 12-O-tetradecanoylphorbol-13-acetate on proliferation and maturation of human breast carcinoma cells (MCF-7): relationship to cell cycle events. AB - Exposure of MCF-7 human mammary carcinoma cells to 12-O-tetradecanoylphorbol-13 acetate (TPA) results in changes in cell morphology and arrest of cell growth. The inhibition of cell proliferation and the increase in cell volume are concentration dependent; these effects are reversible upon removal of the tumor promoting agent. Electron microscopic studies reveal that TPA increases endoplasmic reticulum and induces the appearance of secretory granules. MCF-7 cells treated by TPA therefore present morphological characteristics of secretory cells. These effects of TPA on MCF-7 cells are accompanied by specific disruption of cell cycle events, a block of cells in G1 at the expense of S base, and a delayed passage through G2. Studies in which a cell cycle lock in G1 is produced by tamoxifen show that exposure of such cells to PA produces cell morphological changes and an inability to progress through the cell cycle when estradiol is added. PMID- 3102048 TI - Synergistic inhibition of polyamine synthesis and growth by difluoromethylornithine plus methylthioadenosine in methylthioadenosine phosphorylase-deficient murine lymphoma cells. AB - The antiproliferative effects of the ornithine decarboxylase inhibitor alpha difluoromethylornithine (DFMO) are limited by the inability of the compound to deplete completely cellular polyamine pools. 5'-Deoxy-5'-methylthioadenosine (MeSAdo), the purine end product of the polyamine biosynthetic pathway, is an inhibitor of spermine and spermidine synthesis. Furthermore, a substantial number of human tumors are deficient in MeSAdo phosphorylase, and cannot degrade MeSAdo. It therefore seemed possible that DFMO and MeSAdo could interact synergistically to inhibit polyamine synthesis in MeSAdo phosphorylase-deficient malignant cells. To test this hypothesis, we have analyzed the effects of DFMO, in combination with MeSAdo, on polyamine synthesis and growth in a MeSAdo phosphorylase deficient murine lymphoma cell line (R1.1-H), and a MeSAdo resistant mutant (R1.1 H3). Cultivation of the R1.1-H3 cells in medium containing 250 microM DFMO and 500 microM MeSAdo caused profound depletion of putrescine, spermidine, and spermine, and the accumulation of both decarboxylated S-adenosylmethionine and its acetylated derivative to levels that exceeded by nearly 3-fold the total cellular content of S-adenosylmethionine. Similarly, DFMO sensitized the lymphoma cells to the growth inhibitory effects of MeSAdo. Supplementation of the medium with putrescine, spermidine, or spermine partially protected R1.1-H3 cells from the DFMO-MeSAdo drug combination. It is conceivable that MeSAdo, or related nucleosides, may potentiate the cytostatic effects of DFMO toward MeSAdo phosphorylase-deficient tumors. PMID- 3102050 TI - Effect of intravenous alpha-difluoromethylornithine on the polyamine levels of normal tissue and a transplantable fibrosarcoma. AB - The effect of a continuous i.v. infusion of alpha-difluoromethylornithine (DFMO) on the polyamine metabolism of tumor and normal host tissue was determined. Non tumor-bearing Fischer 344 rats or rats bearing a transplantable fibrosarcoma received continuous infusions of DFMO through a central venous catheter at three dose levels. Treatment with DFMO resulted in a time- and dose-dependent, cytostatic effect on the growth of the tumor. In fibrosarcoma-bearing rats the tumor putrescine levels were reduced after 6 and 12 days of DFMO treatment. Tumor spermidine levels were consistently reduced after 6 and 12 days of treatment with the reduction being dose dependent. The decrease in tumor ornithine decarboxylase activity was dose dependent. Erythrocyte putrescine levels were decreased in tumor- and non-tumor-bearing rats, suggesting that DFMO reduces the tumor contribution to the erythrocyte pool. Erythrocyte spermidine levels of fibrosarcoma- and non-tumor-bearing rats were elevated at the lower DFMO doses administered for 12 days but returned to normal as the dose was increased. Erythrocyte spermine levels were elevated in both groups of rats at all DFMO doses. Although normal host tissue weights were not affected by treatment with DFMO, the putrescine and spermidine levels of liver, spleen, and kidney and ornithine decarboxylase activity of the liver and kidney were decreased. These data demonstrate that i.v. DFMO has a cytostatic effect toward a rapidly growing fibrosarcoma associated with the depletion of both tumor putrescine and spermidine levels. PMID- 3102049 TI - Inhibition of epidermal growth factor binding in rat pancreatic acini by palmitoyl carnitine: evidence for Ca2+ and protein kinase C independent regulation. AB - D,L-Palmitoyl carnitine (PC), an inhibitor of protein kinase C, decreased [125I]epidermal growth factor (EGF) cell-associated radioactivity in rat pancreatic acini. H-7, another inhibitor of protein kinase C, failed to inhibit [125I]EGF binding. Palmitate, carnitine, acetylcarnitine, and 2 tetradecylglycidic acid methyl ester (a specific inhibitor of endogenous PC formation) did not alter [125I]EGF binding. PC conjugated to bovine serum albumin (PC-BSA) decreased [125I]EGF cell-associated radioactivity to the same extent as PC. Neither compound affected the distribution of cell-associated radioactivity into acid-resistant and acid-dissociable compartments. In contrast, cholecystokinin octapeptide (CCK8) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) markedly inhibited the distribution of [125I]EGF into the acid-resistant compartment. Proglumide, a competitive antagonist of CCK8, reversed the inhibitory action of CCK8 but not that of PC-BSA. PC-BSA did not inhibit [125I]insulin binding, and did not enhance amylase release, a Ca2+-mediated effect. Further, its inhibitory effect on [125I]EGF cell-associated radioactivity was not additive with the inhibitory effect of the calcium ionophore A23187. Both PC-BSA and H-7 inhibited Ca2+- and phospholipid-dependent kinase activity in soluble and particulate fractions when added to disrupted acini, but in the particulate compartment only when added to intact acini. These findings suggest that PC-BSA may regulate EGF binding via a novel mechanism that is independent of protein kinase C activation or Ca2+ mobilization. PMID- 3102051 TI - Correlation of dietary aflatoxin B1 levels with excretion of aflatoxin M1 in human urine. AB - Corn and peanut oil (total, 253 samples) were collected from 32 households in Fushui county of the Guangxi autonomous region of the People's Republic of China, where high liver cancer incidence has been reported, every day over a period of 1 week and analyzed for aflatoxin B1 (AFB). A total of 252 urine samples were collected simultaneously from the residents in the households which were shown to have consumed AFB and were analyzed for aflatoxin M1 (AFM) by a competitive direct enzyme-linked immunosorbent assay. A good correlation between total dietary AFB intake and total AFM excretion in human urine was observed during a 3 day study. A regression equation of 0.143 plus 0.0135 multiplied by the amount of AFB consumed was observed. Between 1.23 and 2.18% of dietary AFB was found to be present as AFM in human urine. A good correlation was also observed between the AFB concentration in corn and the AFM concentration in human urine. The results suggest that analysis of AFM in urine by enzyme-linked immunosorbent assay could be used as an index for human exposure of AFB in an extensive epidemiological study. PMID- 3102052 TI - Carcinogenicity of dietary aflatoxin M1 in male Fischer rats compared to aflatoxin B1. AB - Aflatoxin M1 (AFM), an hydroxy metabolite of the potent carcinogenic mycotoxin aflatoxin B1 (AFB) is frequently found in milk and other dairy products. Sufficient amounts of AFM were produced to study the carcinogenicity of this compound. AFM was fed to male Fischer rats starting at 7 weeks up to 21 months of age. Agar-based semisynthetic diets contained 0.0, 0.5, 5.0, and 50.0 micrograms/kg of AFM or 50 micrograms/kg of AFB. Hepatocellular carcinomas were detected in two of 37 rats and neoplastic nodules were found in six of 37 rats fed 50 micrograms/kg AFM between 19 and 21 months. No nodules or carcinomas were observed in the lower AFM dose groups. Nineteen of 20 rats fed a diet containing 50 micrograms/kg of AFB developed hepatocellular carcinomas by 19 months of age. Carcinogenic potency of the aflatoxins was reflected by morphometric quantitation of foci detected in hematoxylin and eosin stained sections. Three rats fed the diet containing 50 micrograms/kg AFM developed intestinal carcinomas. None were observed in other groups. Under the conditions of this experiment AFM was found to be a weak hepatic carcinogen compared to AFB and to possess intestinal carcinogenicity. PMID- 3102053 TI - Sequential studies of skin tumorigenesis in phosphoglycerate kinase mosaic mice: effect of resumption of promotion on regressed papillomas. AB - Most mouse skin papillomas induced by 7,12-dimethylbenz(a)-anthracene initiation followed by 12-O-tetradecanoylphorbol-13 acetate (TPA) promotion are benign promoter-dependent papillomas which regress after cessation of promotion, but some benign tumors (promoter-independent papillomas) do not regress, and a few carcinomas seem to develop from progressive growth of these tumors. We have tested whether a second course of TPA promotion induces regeneration in regressed promoter-dependent papillomas and advances them to malignancy. The regression and regeneration of these papillomas were determined by serial photographs, measurements of coordinates, histopathological evaluation, and X-chromosome linked phosphoglycerate kinase enzyme cellular markers. Most of the regressed promoter-dependent papillomas did not regenerate. However, the second course of TPA promotion induced rapid development of many new papillomas, some of which advanced to promoter-independent papillomas and a carcinoma. This finding suggests that there are more abnormal cells in the initiated mouse skin than those detected with a single course of TPA promotion. PMID- 3102054 TI - Effect of valproic acid therapy on zinc metabolism in children with primary epilepsy. AB - The effect of long-term treatment with valproic acid (VPA) on zinc (Zn) metabolism was studied in 15 children with absence seizures. During treatment with VPA the erythrocyte Zn content was significantly lower than that found in controls matched for sex and age. Plasma and urine values of Zn and of copper were within normal limits. It is suggested that the anticonvulsive action of VPA may be mediated through its effect on the metabolism of Zn in the brain and the concomitant changes in the activity of the enzymes glutamic acid decarboxylase and carbonic anhydrase. PMID- 3102055 TI - Synergy between low-dose chemotherapy and immunotherapy in mouse L1210 leukemia. AB - A high dose of 4 mg/kg of daunorubicin (DAU) given in combination with immunostimulation by the P40 immunomodulatory fraction of Corynebacterium granulosum and glutaraldehyde (GA)-treated tumor cells coupled with tetanus toxoid (P40 + GA-L1210-Tet) was more effective than DAU alone for treatment of L1210 mouse leukemia. A combination of low doses of DAU (0.0625-0.25 mg/kg) and P40 + GA-L1210-Tet was more effective than either P40 + GA-L1210-Tet or DAU alone. The cured mice were resistant to challenge with a high tumorigenic dose of L1210 tumor cells. A combination of various doses of mitomycin (1-4 mg/kg) with P40 + GA-L1210-Tet was more effective than mitomycin alone and was at least as effective as P40 + GA-L1210-Tet alone. Administration of DAU (0.5-4 mg/kg) to noninoculated C57BL/6 X DBA/2 mice resulted in increase of stimulation in vitro of collected spleen cells by mitogens. PMID- 3102056 TI - Second-line chemotherapy of stage III-IV ovarian carcinoma: a randomized comparison of melphalan to melphalan and hexamethylmelamine in patients with persistent disease after doxorubicin and cisplatin. AB - A total of 205 women with stage III or IV ovarian cancer who had persistent disease after initial treatment with doxorubicin and cisplatin were randomized to receive melphalan (8 mg/m2 orally for 4 days) or the combination of melphalan (6 mg/m2 for 4 days) and hexamethylmelamine (120 mg/m2 for 14 days) every 4 weeks. Only one of 64 patients with measurable disease had an objective response. The major determinants of survival after randomization were the amount of residual disease after initial chemotherapy and the type of response to initial chemotherapy. There was no overall difference in survival between the two chemotherapy regimens, but the small group of patients whose disease progressed on initial chemotherapy survived significantly longer when treated with the two drug combination. Neither of these regimens provided effective therapy for women whose disease was not eliminated by first-line treatment. However, the superior results obtained in one subgroup with the addition of hexamethylmelamine suggest that the place of this agent in treating ovarian cancer should be carefully evaluated. PMID- 3102057 TI - Hexamethylmelamine: a critical review of an active drug. AB - Hexamethylmelamine is an s-triazine that began clinical trials during the 1960s based on its level of antitumor activity in murine tumor models. Phase I studies were performed using an oral formulation given in divided doses for varying numbers of days. The most frequently reported toxicities included nausea, vomiting, abdominal cramps, anorexia, weight loss and malaise. Less frequently reported toxicities were anemia, thrombocytopenia, leucopenia and peripheral neuropathy. Clinical antitumor activity was noted in the phase I studies in a variety of tumor types. Since then a large number of studies have been performed using hexamethylmelamine as a single agent and in a variety of combinations. Unfortunately, almost none of these studies sought to define the utility of this drug relative to other treatments for the diseases in which it showed activity, or to define the contribution of this drug to the activity of any given combination. Thus its role in the treatment of patients with malignancies remains undefined. PMID- 3102058 TI - Preparation of 8-methoxycarbonyloctyl glycosides of alpha-D-mannopyranose, 2-O alpha-mannopyranosyl-alpha-D-mannopyranose, beta-D-galactofuranose, and 3-O-beta D-galactofuranosyl-alpha-D-mannopyranose. AB - The 8-methoxycarbonyloctyl glycosides of alpha-D-mannopyranose, 2-O-alpha mannopyranosyl-alpha-D-mannopyranose, beta-D-galactofuranose, and 3-O-beta-D galactofuranosyl-alpha-D-mannopyranose were prepared as intermediates for the synthesis of complexes with the general structure mono-(or di-)saccharide-lipid spacer-protein having possible antigenic and immunogenic activity in respect to infection with Trypanosoma cruzi. Tri-O-acetyl-1,2-O-(1-methoxyethylidene) derivatives of D-mannopyranose and D-galactofuranose were treated with alcohols in the presence and absence of mercuric bromide to give orthoesters which rearranged into glycosides. PMID- 3102059 TI - Analysis of the chain length of oligomers and polymers of sialic acid isolated from Neisseria meningitidis group B and C and Escherichia coli K1 and K92. AB - A series of (2----8)-alpha-, (2----9)-alpha-, and alternate (2----8)-alpha- and (2----9)-alpha-linked oligomers of sialic acid (N-acetylneuraminic acid, NeuNAc) was prepared by digestion with bacteriophage or by partial hydrolysis at pH 7.0 and 100 degrees of polymers of sialic acid produced by Neisseria meningitidis and Escherichia coli. The oligosaccharides were purified by gel filtration or by anion-exchange chromatography, and their chain lengths were determined by colorimetric measurement of the formaldehyde released from the non-reducing end residue after periodate oxidation, radiolabelling of the reducing end residue by reduction with borotritiide, and determination of the ratio of the non-reducing end and internal residues by g.l.c. of the trimethylsilyl derivatives of the methyl ester methyl beta-ketosides. 1H-N.m.r. spectroscopy was used to confirm the chain length of two oligosaccharides. These methods were used to determine the average chain-length of the sialic acid polysaccharides produced by N. meningitidis and E. coli and the percentage of chains with covalently bound lipid moieties at the reducing end. PMID- 3102060 TI - Structural studies of a teichoic acid from Streptococcus agalactiae type III. AB - An unusual type of teichoic acid has been isolated from Streptococcus agalactiae type III. It has the same backbone as the lipoteichoic acid from Streptococcus faecalis, but is devoid of fatty acid residues, a phosphatidyl group, and substituents in the poly(glycerol phosphate) side-chain. The following structure, with n approximately 20, was determined mainly with the aid of n.m.r. spectroscopy. (Formula: see text) PMID- 3102061 TI - Fractionation of the cellulolytic enzymes produced by a species of Monilia; purification and properties of an extracellular beta-D-glucosidase. AB - Extracellular cellulolytic enzymes produced by a species of Monilia could be fractionated by chromatography on SP-Sephadex, Con A-Sepharose, and cellobiose Sepharose. These methods did not separate the beta-D-glucosidases (beta-D glucoside glucohydrolases, EC 3.2.1.21) from the cellulases and xylanases within a single purification step. Fractionation by isoelectric focusing on a flat-bed granulated gel gave all of the beta-D-glucosidase activity in a single zone isoelectric at pH 8-9. The beta-D-glucosidase could be further purified to homogeneity by column isoelectric focusing at pH 8.0-10.5, and gel filtration on Biogel P-100. The purified beta-D-glucosidase showed optimal activity at pH 4-5 and 50 degrees, was isoelectric at pH 8.87, and had a molecular weight of 46,600. SDS-Polyacrylamide-gel electrophoresis demonstrated that the beta-D-glucosidase was not dissociated into subunits and, hence, consisted of a single polypeptide chain. The enzyme is considered a glycoprotein, as it binds to Con A-Sepharose. The beta-D-glucosidase hydrolyzed (1----2)-, (1----4)-, and (1----6)-beta-D glucosidic linkages but not cellulose. Nitrophenyl beta-D-glucopyranosides and beta-D-xylopyranosides were also degraded. The beta-D-glucosidase was competitively inhibited by D-glucose (Ki 0.67 mM). PMID- 3102062 TI - In vitro and in vivo release of cytostatic factors from Lactobacillus casei elicited peritoneal macrophages after stimulation with tumor cells and immunostimulants. AB - The effect of tumor cells and immunostimulants on the release of cytostatic factors (CF) from Lactobacillus casei YIT 9018 (LC)-, Corynebacterium parvum (CP) or peptone-elicited peritoneal macrophages (PM) was investigated in vitro and in vivo. Significant release of CF into the culture medium from PM elicited with LC was induced by seven of eight mitomycin C-pretreated tumor cell lines and not by normal spleen cells, while no CF was released extracellularly from peptone elicited PM given the same stimulus. CF were released from LC-elicited PM (LCEPM) after stimulation with LC, bacille Calmette-Guerin, streptococcal preparation OK 432, fucoidan or lipopolysaccharide, and LC but not CP induced CF production in the peritoneal cavities of LC- or CP-primed mice. The release of CF from LCEPM after stimulation with mitomycin C-pretreated 3T12-3 cells was inhibited by D mannose and not by L-fucose. L-Rhamnose and mannose 6-phosphate, but not D mannose or L-fucose, caused the release of CF from the PM. It was suggested that the release of CF from activated PM is caused by stimulation by some tumor cells, sugars, or bacterial immunostimulants, D-Mannose and L-rhamnose on the surface of tumor cells or bacteria, respectively, may plan an important role in the release of CF from activated macrophages. PMID- 3102063 TI - I-Ad antigen expression of pyran copolymer-induced peritoneal cells in tumor vaccine-primed mice and its association with the host antitumor response. AB - Mice inoculated IP with L1210 murine leukemia vaccine and subsequently with pyran copolymer-induced macrophages (pyran-M phi) lived for a prolonged time after live L1210 inoculation IP. Pyran-M phi as tentatively identified by anti-AcM.1 monoclonal antibody expressed I-Ad antigen in tumor vaccine-primed recipient mice and contributed to maintaining I-Ad antigen positive (I-Ad+) macrophages at high cell density in the peritoneal cavity of recipient mice. The relevance of these I Ad+ cells to the host antitumor response was examined by experiments in which I Ad+ cell density in the peritoneal cavity and host antitumor response behaved in a parallel fashion. Human interferon-alpha A/D, an agent selectively inhibiting Ia antigen expression, and silica, a general antimacrophage agent, strongly suppressed I-Ad antigen expression of peritoneal macrophages of tumor vaccine primed and pyran-M phi-inoculated mice and, consistently with this, the antitumor response was nullified in these mice. Tumor vaccine-primed mice inoculated with sodium caseinate or thioglycollate-induced peritoneal cells did not survive L1210 inoculation and, in these mice, I-Ad+ peritoneal macrophages were suppressed in number as compared with those of tumor vaccine-primed and pyran-M phi-inoculated mice. These results warrant further study on the contribution of I-Ad+ macrophages to pyran copolymer-induced augmentation of the antitumor response in tumor vaccine-primed mice. PMID- 3102064 TI - Estimation of left ventricular volume and mass by magnetic resonance imaging: comparison with quantitative biplane angiocardiography. AB - Magnetic resonance imaging (MRI) is well suited for the delineation of cardiac anatomy. In this study an estimation of left ventricular volume and muscle mass by MRI was attempted, using an iron-shielded resistance magnet (Bruker) with 0.23 T. Images were obtained with ECG gating. For image-processing our own software program was used. Slice images were 8 mm thick and spaced 16 mm. Volumes were standardized for a "normal" LV. Muscle mass was calculated directly from the systolic image as the difference between inner and outer ventricular outline. There was a wide range of volumes and mass (100-300 ml, 200-500 g). For comparison and validation conventional biplane left ventriculography was used. Fourteen patients were studied with MRI, but satisfactory studies were obtained in only 7. Correlation of MRI and angiographic volumes was good (r = 0.84). For left ventricular mass it was excellent (r = 0.94). Ventricular walls and cavities were clearly outlined. Even minor details of anatomy were recognized. Limitations of MR study included a narrow space for the patient within the system and the long duration of data acquisition time. PMID- 3102066 TI - MRI diagnosis of aortocaval fistula secondary to ruptured infrarenal abdominal aortic aneurysm. AB - MRI was utilized to demonstrate the exact site of fistula between a ruptured saccular aneurysm of the infrarenal abdominal aorta and the inferior vena cava in a 64-year-old man. PMID- 3102065 TI - CT of ruptured aneurysm of aberrant right subclavian artery. AB - This paper presents the first description of a ruptured aneurysm of an aberrant right subclavian artery. CT clearly demonstrated the vascular malformation as well as the existence of a bilateral hemothorax. PMID- 3102067 TI - Retrieving the Amplatz retrievable vena cava filter. AB - The new Amplatz retrievable filter was placed 15 times into the inferior vena cava (IVC) of 7 dogs. Retrieval of the filter was attempted in 11 cases after 1 week and in 3 cases after 2 weeks. The retrieval was successful and without complication in all 14 cases. The 15th placement resulted in thrombotic occlusion of the IVC, and no retrieval was attempted. PMID- 3102068 TI - Misplacement of a vena cava filter in the retroperitoneum. AB - An inferior vena cava filter was misplaced into the pericaval retroperitoneum. This was probably secondary to placement into and avulsion of the right spermatic vein. The filter delivery system was modified, and such misplacement should now be impossible. PMID- 3102069 TI - Cardiovascular computed tomography (cine CT) of abnormal left ventricular wall motion due to epicardial pacing electrodes. AB - A patient with an abnormal cardiac silhouette on chest X-ray was studied by fast cardiovascular computed tomography (cine CT). The location of epicardial pacing electrodes and their relationship to myocardial wall motion abnormalities were examined. This eliminated the need for cardiac catheterization. PMID- 3102070 TI - Activation of kinin-prekallikrein system after infusion of factor VIII concentrates in hemophilic patients. AB - Possible changes in the kinin-prekallikrein system after infusion of factor VIII concentrate were studied in seven patients with severe hemophilia. The functional and immunological activities of factors XI and XII, prekallikrein, high molecular weight kininogen, and C-1-esterase inhibitor were measured before and at 0.5, 2, 6, and 12 hours after infusion of 50 U/kg of factor VIII concentrate. A significant decrease (P less than 0.05) in the functional and immunological activities of prekallikrein was observed at 0.5 and 2 hours after factor VIII administration. The other proteins did not change. The results suggest that the kinin system is activated after infusion of high doses of factor VIII concentrate, although clinical evidence of such activation by these changes was not detected. PMID- 3102071 TI - Growth hormone-releasing factor (GRF)-like immunoreactivity in sensory ganglia of the rat. AB - Growth hormone-releasing factor (GRF)-like immunoreactivity has been demonstrated in the trigeminal and spinal ganglia of fetal, young and adult rats by use of peroxidase-antiperoxidase immunohistochemistry. GRF-like-immunoreactive cells first appear during the second half of embryonic life, as early as day 17. In untreated animals the GRF-immunoreactive elements form approximately 1% of all ganglion cells in the trigeminal and spinal ganglia; their numbers do not change significantly during development. The granular immunoreaction product is confined to perikarya, especially to the perinuclear region. Nerve fibers displaying GRF like immunoreactivity were found neither in the ganglia, nor in the corresponding central and peripheral areas of termination. The possible role of GRF in sensory ganglia is discussed. PMID- 3102072 TI - Cigarette smoking during coronary angiography: diffuse or focal narrowing (spasm) of the coronary arteries in 13 patients with angina at rest and normal coronary angiograms. AB - To evaluate the acute effects of cigarette smoking on coronary arteries (CA), repeated coronary angiograms were performed in 13 patients with angina at rest and with normal coronary angiograms at basal state, during smoking, and then after methylergometrine (MEM) and after intracoronary nitroglycerin. Smoking induced anginal pain in three patients, triggered spasm (focal narrowing) in six, and/or an abnormal segmental diffuse narrowing (greater than 30%) in eight. The narrowing of the left CA was on average -21 +/- 13% (P less than 0.001), with more important narrowing of the mid-left anterior descending (-29 +/- 19%, P less than 0.001). The mean of the maximal segmental narrowing by patient was -34 +/- 13% (P less than 0.001). MEM produced similar effects and induced focal CA spasms in nearly the same patients at the same sites. Cigarette smoking may induce vasoconstrictive effects on CA in patients with rest angina and normal coronary angiograms. This action is not dose-dependent and may be initiated by less than one cigarette. These observations offer a new perspective for the understanding of the role of smoking in the precipitation of coronary events. PMID- 3102073 TI - Phagocytosis and inflammatory stimuli induce GM-CSF mRNA in macrophages through posttranscriptional regulation. AB - Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is a powerful growth and differentiation factor which acts on hematopoietic progenitor cells and also activates differentiated granulocytes and macrophages. This study shows that mouse peritoneal macrophages can be induced to accumulate GM-CSF mRNA and to release GM-CSF by inflammatory agents (lipopolysaccharide, fetal calf serum, thioglycolate broth); phagocytosis; and adherence in the presence of fibronectin. GM-CSF mRNA accumulation, which is totally prevented by the corticosteroid dexamethasone and by interferon-gamma, is not accompanied by changes in the gene's transcriptional level. No interleukin 3 (multi-CSF) mRNA is detectable in induced macrophages. These findings have implications in the understanding of hematopoiesis and of the inflammation and repair process. PMID- 3102074 TI - Monoclonal antibodies against Drosophila ovaries: their reaction with ovarian and embryonic antigens. AB - A library of monoclonal antibodies (MAbs) against Drosophila ovarian antigens was established. Each of the MAbs was characterized by its immunohistochemical binding pattern to sections from egg chambers at various stages of oogenesis. Sixteen of the 18 MAbs were found to bind to antigens in mature oocytes. Among the 16 antigens, two were also located in cytoplasm of cell types in the egg chamber other than the oocyte, at all stages of oogenesis. Four made their appearance in nurse cell cytoplasm at mid-vitellogenic stages and shifted to oocyte cytoplasm at a later stage, and ten appeared at the vitellogenic stage and confined their distribution to oocyte cytoplasm. All these antigens were distributed evenly in cytoplasm of mature oocytes. However, some of these antigens were noticed to change their distribution during early embryogenesis as to be localized in a specific region of embryos. PMID- 3102075 TI - Clonal analysis of human tumor infiltrating lymphocytes reactive with autologous tumor cells: different target cell specificities of NK-like and cytotoxic T-cell clones. AB - Lymphocytes, derived from surgically resected lung carcinoid tissue, were stimulated in mixed culture with irradiated autologous tumor cells (MLTC). The autologous MLTC-stimulated lymphocytes were found to have killing activity against both autologous tumor cells and NK-sensitive target cells. The lymphoblasts generated during MLTC were isolated and cloned under limiting dilution conditions in the presence of interleukin 2. The cloned cell lines were analyzed for cell phenotype and tested for cytotoxic activity. Three cloned cell lines, out of 19 tested, were found to be cytotoxic either against NK-sensitive target cells (natural killers) or the autologous tumor cells. Two clones, having OKT8 phenotype, caused no lysis of the autologous tumor cells, though both exerted NK-like activity against K562 cells. Only one clone with OKT4 phenotype showed specific cytotoxic activity against the autologous tumor, but no NK-like activity against a panel of tumor target cells. These results suggest the coexistence of two types of antitumor cytotoxic lymphocytes at the tumor site: precursors of NK-like cells and specific cytotoxic T cells. Target cell specificity provided a means of distinguishing between the two types. PMID- 3102076 TI - Characterization of the T3+T4+T8+ thymocyte intermediate in vitro. AB - Sensitive two-color fluorescence staining and cell-sorting techniques were used to isolate a T4+T8+ thymocyte subpopulation with high T3 density from human thymocyte cultures. Previously, this population was shown to give rise to both T4+T8- and T8+T4- thymocytes. In the present study, this T3+T4+T8 population was shown to be functionally as well as phenotypically distinct from either T8+T4- cells or T4+T8- cells present in the same culture. The T3+T4+T8+ cell had intermediate cytotoxic capacities relative to T8+T4- and T4+T8- thymocyte fractions. The proliferative capacity of the T4+T8+ population although less than that of the T8+T4- subset exceeded the proliferative response of the T4+T8- population. The time of appearance of large numbers of T3+T4+T8+ cells in culture as well as functional properties exhibited by T3+T4+T8+ cells are consistent with the notion that the T3+T4+T8+ cell represents an activated intermediate in thymocyte differentiation. The T3+T4+T8+ thymocyte may be an important intermediate in in vivo as well as in in vitro thymic differentiation. Moreover, the analysis of its functional properties may contribute to an understanding of functional responses exhibited by the most mature (T3+) population isolated from human thymus. PMID- 3102077 TI - Down regulation of human monocyte differentiation antigens by interferon gamma. AB - The role of IFN-gamma in the activation and differentiation of human peripheral blood monocytes was investigated. Recombinant IFN-gamma induced a decrease in the expression of monocyte differentiation antigens (Mo2 and 63D3) and, to a lesser extent, the C3bi receptor. Conversely, class II histocompatibility antigen expression increased on monocytes exposed to IFN-gamma. The antigen modulating effect of IFN-gamma was maximal on freshly isolated monocytes, with diminished potency if added to monocytes that had been cultivated in vitro for 1 to 3 days. Experiments to determine the fate of the down-regulated antigens on interferon treated cells failed to demonstrate intracellular antigen due to internalization. We suggest that Mo2 and 63D3 may be considered "inverse" activation antigens; i.e., their expression is decreased in monocytes activated by interferon. PMID- 3102079 TI - Enhancement of human natural killer activity by the monoclonal Leu-11 antibodies. AB - The Fc receptor for IgG on human natural killer (NK) cells can be identified by a series of murine monoclonal antibodies. When these antibodies with IgG1 isotype (e.g., Leu-11a and Leu-11c), but not with IgM (e.g., Leu-11b and VEP13), were added to NK assay culture against K562 targets of 4-hr analysis, a considerable enhancement of NK activity was induced. An enhancement was shown at a concentration of up to 10(-5) mg/ml of Leu-11a. Furthermore, the present experiments demonstrated that many established cell lines with diverse cell origins expressed the Leu-11 antigens, and enhancement of NK activity by Leu-11 was induced when these Leu-11+ cell lines were used as targets in NK assays. The results that Leu-11a caused an increase in effector-to-target cell conjugates, and that F(ab')2 of Leu-11a was effective in enhancement of NK activity, but the Fab was not, indicated that Leu-11 might become a linkage between the effector and target cells. Significance of this phenomenon was discussed regarding practical application of Leu-11 antibodies in laboratory experiments and in clinical studies. PMID- 3102080 TI - Increased ornithine decarboxylase activity and polyamine biosynthesis are required for optimal cytolytic T lymphocyte induction. AB - The objective of the present investigation was to evaluate the requirement for increased ornithine decarboxylase (ODC) activity and polyamine biosynthesis in the induction of cytolytic T lymphocytes (CTL). In this regard, we have utilized alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC. DFMO treatment completely abrogated Con A-induced NW T-cell ODC activity. Similarly, DFMO treatment reduced putrescine and spermidine biosynthesis 100 and 87% respectively by the end of a 48-hr incubation period. Polyamine depletion reduced the Con A-mediated polyclonal induction of CTL by 52 and 81% at 24 and 48 hr of culture, respectively. The effect of DFMO on CTL induction could be reversed by the addition of exogenous putrescine. These data indicate that the observed effects of DFMO on CTL induction were mediated through inhibition of polyamine biosynthesis. Therefore, increased ODC activity and polyamine biosynthesis are required for optimal CTL induction. Furthermore, polyamine depletion did not impair IL-2 production; however, IL-2-dependent proliferation was reduced. These data are the first to discriminate between the requirement for polyamines with regard to IL-2 responsiveness, rather than IL-2 production, during a primary T cell mitogenic response. PMID- 3102078 TI - Anti-idiotypic T lymphocyte responsiveness in murine Schistosomiasis mansoni. AB - Pooled sera from CBA/J mice infected for greater than or equal to 16 weeks with the blood fluke Schistosoma mansoni were immunoaffinity purified using soluble schistosome egg antigens (SEA) coupled to Sepharose 4B. The bound and then eluted fraction was shown to contain only immunoglobulins and to have anti-SEA activity. These anti-SEA antibodies stimulated proliferation of lymph node cells from mice infected with S. mansoni for 8, 12, or greater than or equal to 16 weeks but not from uninfected mice. The cells stimulated by anti-SEA antibodies were nylon wool adherent, Thy-1.2+, L3T4+, Lyt-2-lymphocytes. Immunoglobulins without anti-SEA activity isolated from the sera of syngeneic uninfected mice were not stimulatory for cells from normal or infected animals. Thus the responding T cells appear to be stimulated by the idiotypes expressed on the syngenic anti-SEA antibodies. These data present evidence for anti-idiotypic cellular reactions in murine schistosomiasis that could play important immunoregulatory roles in this disease. PMID- 3102081 TI - Direct induction of lymphocyte killing by calcium ionophore and phorbol ester treatment. AB - To analyze transduction mechanisms in human lymphocyte killing, intracellular Ca2+ levels were increased by ionophore A23187 treatment and protein kinase C activated by phorbol ester 12-O-tetradecanoylphorbol-acetate (TPA). Drugs were tested either alone or in combinations on effector cells active in natural, antibody-dependent, and lectin-dependent killing. TPA suppressed killing in all systems at 100 ng/ml whereas A23187 was only suppressive for NK killing at concentrations higher than 0.1 microM. TPA combined with A23187, above 10 ng/ml and 0.5 microM, respectively, induced killing of all tested target cell lines with a slower kinetic than NK killing of K562 cells. Drug-induced killing did not increase optimal lectin and antibody-dependent killing and was demonstrated most easily on NK-resistant target cell lines. Fractionation of effector lymphocytes into NK cell-depleted, T3-positive and NK cell-enriched, T3-negative cells demonstrated that similar levels of TPA/A23187-dependent killing could be induced in both fractions. It is concluded that TPA/A23187 induce normal lymphocytes to nonselective killing of different target cells in similarity to the triggering effect these drugs have in many other cell systems. Whether the induced killing is representative of NK killing is discussed in relation to the presence of other potential effector cells and effector molecules in peripheral blood lymphocytes. PMID- 3102082 TI - Separation and purification of lymphocyte chemotactic factor (LCF) and interleukin 2 produced by human peripheral blood mononuclear cells. AB - Two T-cell chemotactic factors, lymphocyte chemotactic factor (LCF) and interleukin 2 (IL-2), were separated and characterized from culture supernatants of concanavalin A-stimulated human peripheral blood mononuclear cells. LCF was purified approximately 7800-fold to homogeneity from culture supernatant using gel filtration and high-performance liquid chromatography (HPLC). LCF was found to be distinct from both IL-2 and interleukin-1. Sephadex G-100 gel filtration of crude supernatants from concanavalin A-stimulated mononuclear cells showed two molecular weight regions of T lymphocyte chemotactic activity. A 10,000- to 25,000-Da region contained both IL-2 and LCF and a 45,000- to 75,000-Da region contained only a high molecular weight form of LCF. Both high and low molecular weight species of LCF eluted with 40-44% acetonitrile from a reversed-phase C18 HPLC column. IL-2 present only in the low molecular weight region eluted from the C18 column with 65-75% acetonitrile. The migration of T lymphocytes to IL-2 was totally inhibited by anti-interleukin 2 receptor antibody while the response of T cells to LCF was unaffected. LCF eluting off the C18 column was purified to homogeneity by two subsequent cycles of gel filtration HPLC. The resultant protein showed a single band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis corresponding to a molecular weight of 10,500. The data presented here demonstrate that IL-2 and LCF are distinct lymphocyte chemotactic factors and although they are not readily separable from crude supernatants by molecular sieve chromatography, they can easily be distinguished by reversed-phase HPLC. PMID- 3102083 TI - Increased stability of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy 7,8,9,10-tetrahydrobenzo [a]pyrene through interaction with subcellular fractions of rat liver. AB - The rate of hydrolysis of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy 7,8,9,10-tetrahydrobenzo [a]pyrene (BPDE) to tetrahydroxy derivatives (tetrols) in the presence of various subcellular fractions of rat liver was investigated. Microsomes and nuclei increased the half-life of BPDE in a concentration dependent manner whereas cytosol had no such effect. The presence of 1 mg microsomal protein/ml increased the half-life of BPDE from 4 to 60 min at 22 degrees C and from 1.5 to 20 min at 37 degrees C. Nuclei equivalent of 500 micrograms DNA/ml increased the half-life from 1.9 to 3.6 min at 37 degrees C. Liposomes prepared from microsomal lipids mimicked the effect of microsomes indicating that BPDE is stabilized primarily by interacting with lipids. The significance of these interactions for the stability of BPDE in an intact cell system was evaluated by using isolated hepatocytes. In these cells the half-life of BPDE was substantially shorter (1 min at 5 X 10(6) cells/ml) than in buffer (3 min). However, hydrolysis of BPDE to tetrols was a minor reaction (less than or equal to 3% of added BPDE at a cell density greater than or equal to 5 X 10(6) cells/ml) and the main route of elimination (greater than or equal to 75%) was through conjugation with glutathione. PMID- 3102085 TI - Effects of clofibrate on hyperlipidemia induced by polychlorinated biphenyls and elimination of polychlorinated biphenyls accumulated in rat tissues. PMID- 3102084 TI - The relationship between ionization potential and prostaglandin H synthase catalyzed binding of aromatic hydrocarbons to DNA. AB - A series of polycyclic aromatic hydrocarbons (PAH) with ionization potentials (IP) ranging from 7.7 to 6.96 eV were examined for their ability to bind to DNA in vitro via the prostaglandin H synthase (PHS)-catalyzed co-oxidation of PAH. A relatively low IP was required for significant binding of PAH to DNA to occur. PAH with IP below approximately 7.35 eV were active in the binding reaction, while those with IP at or above 7.35 eV exhibited much lower levels of binding. Among the PAH which bound at high levels, there was no correlation between the extent of binding and IP. The results suggest that the prostaglandin H synthase mediated binding of PAH to DNA occurs by one-electron oxidation, similarly to previously reported horseradish peroxidase (HRP)-catalyzed binding of PAH to DNA. PMID- 3102086 TI - [Doses of oral mannitol for intestinal evacuation]. PMID- 3102087 TI - Recent experience with ifosfamide/mesna in solid tumors. International satellite symposium to the 3rd European Conference on Clinical Oncology. Stockholm, June 1985. Proceedings. PMID- 3102088 TI - Ifosfamide plus mesna with and without adriamycin in soft tissue sarcoma. AB - Early results with ifosfamide plus mesna in soft tissue sarcoma showed an initial response rate of 38% in 42 patients. All these patients treated at The Royal Marsden Hospital plus 30 more (total 67) have now been analysed. Single doses of 5 or 8 g/m2 ifosfamide were given over 24 h by infusion in dextrose saline together with 400 mg/m2 or 600 mg/m2, respectively, of mesnum every 4 h to give a total of 9 doses. A diuresis of 200 ml/hour was maintained during therapy. Treatment was repeated 3-weekly. CR was seen in 6 and PR in 10 patients. More recently doxorubicin was added to ifosfamide therapy in an attempt to improve on these results. At first only 20 mg/m2 doxorubicin was given but this was escalated to 40 mg/m2 and 60 mg/m2. Mesna has been given in higher dosage (5 g/m2 over 24 h), but otherwise the schedule is as above. In all 60 patients have been treated and most are now evaluable for response. Encephalopathy has been seen with both regimens. The incidence and patient characteristics are reported. PMID- 3102090 TI - High-dose ifosfamide alone and in combination for solid malignancies in childhood. PMID- 3102089 TI - Cyclophosphamide versus ifosfamide: preliminary report of a randomized phase II trial in adult soft tissue sarcomas. AB - One hundred and seventy-one patients with advanced soft tissue sarcoma entered a randomized crossover phase II study comparing cyclophosphamide (CYCLO) with a new analogue, ifosfamide (IFOS), both administered as 24 h i.v. infusions every 3 weeks. The doses used were CYCLO 1.5 g/m2 and IFOS 5 g/m2, with provision for dose escalation. All patients received mesna 400 mg/m2 as an i.v. bolus 4 hourly X 9 doses, commencing at the start of the oxazophosphorine infusion. Patients who had received previous chemotherapy were eligible provided this did not include a classical alkylating agent. There were 22 patients who were ineligible, and response could not be evaluated in 12 additional patients. IFOS produced two complete and ten partial remissions, for an overall response rate of 18%. CYCLO was significantly (P = 0.04) less active, producing one complete and five partial remissions, an overall response rate of 9%. Stabilization of disease was similar in both arms (27% and 24% respectively), but fewer patients showed progression on IFOS. The response rate was higher (20% vs 5%) for patients who had not received previous chemotherapy, and also for female compared with male patients (21% vs 5%). When only patients who had not received previous chemotherapy were considered, the respective response rates for IFOS and CYCLO were 24% and 15%. There were no responses in previously treated patients receiving CYCLO. There were four partial responses in 33 patients crossing from CYCLO to IFOS, but no responses in 18 patients receiving CYCLO after IFOS. Leucopenia was significantly more pronounced (P = 0.0004) with CYCLO, both after the first course and throughout treatment, although the incidence of severe infections, 6%, was the same in both arms. Nausea and vomiting were more severe with IFOS (P = 0.022), but other toxicities were mild. Grade 1 or 2 bladder (haematuria) or renal (rise in serum creatinine) toxicity was slightly more frequent with IFOS (7 vs 3 patients) and was a reason for stopping treatment for one patient in each arm. Three episodes of mild to moderate drowsiness after IFOS were reported, but no severe encephalopathy. A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination with such active agents as adriamycin. PMID- 3102091 TI - Treatment of advanced soft tissue and osteogenic sarcomas with continuous infusion of ifosfamide and mesna. PMID- 3102092 TI - Ifosfamide in advanced pancreatic cancer. A 5-year experience. AB - Ifosfamide was studied in advanced pancreatic tumor at the National Cancer Institute, Cairo. Over five years, 25 patients received a daily dose of 1.8 g ifosfamide for five days, courses reported every 21 days. Complete remission was achieved in 1 patient and partial remission in 14 patients, an overall result of 60%, average duration of response being 12+ months. Mesna was used for uroprotection. PMID- 3102093 TI - Inhibition of methionine uptake by methotrexate in mouse leukemia L1210 cells. AB - Methionine-auxotrophic L1210 cells were used to study the effect of methotrexate (MTX) on methionine uptake and metabolism. MTX was shown to inhibit amino acid transport systems and cause a decrease of methionine uptake into L1210 cells. Conversely, a nonmetabolizable amino acid analogue reduced MTX uptake into L1210 cells. MTX also blocked the transfer of the beta carbon from serine into methionine. Therefore, methionine deprivation may be an additional mechanism of action for MTX in methionine-auxotrophic tumor cells. PMID- 3102094 TI - Problems of pharmacokinetic studies on alpha-difluoromethylornithine in mice. AB - The pharmacokinetics of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of polyamine biosynthesis, were investigated in BALB/c (nude) mice after i.p. injection and after oral administration of radiolabeled drug. After i.p. injection the compound was rapidly cleared from the serum (t1/2 alpha = 14 min; t1/2 beta = 2.1 h) and from tissues such as muscle, liver and kidney (t1/2 alpha = 30-60 min; t1/2 beta = 2.1 h). DFMO concentrations were proportional to the administered dose (10-2000 mg/kg) in both serum and tissues. Oral administration of DFMO was carried out by dissolving the compound in drinking water at a concentration of 20 g/l. Studies on the distribution showed that DFMO did not accumulate preferentially in any particular tissue. An extremely wide variation in the dose actually achieved in different animals was observed; this ranged from 350 to 2800 mg/kg for a 14-h treatment period. A significant correlation (r = 0.83-0.92) between the dose of DFMO, calculated from the consumption of drinking water for each individual animal, and the DFMO concentrations in serum, muscle, spleen, liver and kidney was found. Similarly, it was shown that oral administration of DFMO during the daytime resulted in 10- to 15-fold lower levels than administration during the night. After discontinuation of treatment DFMO levels in serum and tissues decreased by 50% in approximately 6 h. From these results it is concluded that the optimal treatment schedule of mice with DFMO (or other drugs with similar pharmacodynamic properties) consists in a combination of oral administration via the drinking water and additional i.p. injection (during the daytime). Furthermore, the drug intake of the individual animals should be monitored to check whether the experimental requirements are actually fulfilled. PMID- 3102095 TI - UFT for head and neck cancers: its tissue concentrations and effects on lymphocyte subpopulations. AB - UFT, a combination of the masked compound of 5-fluorouracil (FT-207) and uracil, was given to head and neck cancer patients for 1 week preoperatively and for 8 weeks postoperatively. Drug concentrations were examined in the surgically removed tissues. The concentrations of FT-207, 5-fluorouracil, and uracil were higher in tumor tissues than in normal tissues. The lymphocyte subpopulations were assessed by cytofluorometry with monoclonal antibodies. There was no evidence that adjuvant chemotherapy with UFT specifically suppresses immunocompetent cells. We therefore conclude that further clinical evaluation of adjuvant chemotherapy with UFT would be worthwhile. PMID- 3102097 TI - Promotion of skin tumours by TPA in the progeny of mice exposed pre-natally to DMBA. AB - Pregnant SHR mice were treated once with 7,12-dimethylbenz[a]anthracene (DMBA) on day 17-19 of gestation, and F1 and F2 descendants received multiple skin applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) twice a week for 24 weeks beginning at 12 weeks of age. Post-natal promoter treatment resulted in a high incidence of skin tumours in F1 and F2 mice (37.3 and 19.7%, respectively), whereas only 6.6% of control animals treated with TPA only developed skin tumours. DMBA was shown previously to be capable of initiating skin carcinogenesis transplacentally; however, our results on the second generation provide suggestive evidence of hereditary transmission of at least part of the initiating action of this carcinogen. PMID- 3102096 TI - Absence of interaction between furosemide and mitomycin C. AB - The possible interaction between furosemide and mitomycin C (MMC) was studied in five patients. The pharmacokinetics of MMC were studied using an HPLC assay. Furosemide was administered prior to, or 120 min after MMC. Furosemide did not change the pharmacokinetics of MMC, nor did it change the amount of MMC excreted in the urine. There appears to be no interaction between the two drugs. PMID- 3102098 TI - Reducing substrate activity of some aromatic amines for prostaglandin H synthase. AB - The ability of eight different aromatic amines to serve as reducing substrates for the conversion of 5-phenyl-4-pentenyl-hydroperoxide to 5-phenyl-4 pentenylalcohol by prostaglandin H synthase (PHS) was studied. The methodology used a direct assay for the reduction of hydroperoxide to alcohol and allowed an assessment of the reducing substrates' efficiency as a donor of electrons to the peroxidase component of highly purified PHS. The eight amines tested include, 1 naphthylamine, 2-naphthylamine, 2,4-diaminoanisole, 2,5-diaminoanisole, 2 aminofluorene, 2-acetylaminofluorene, 2-amino-anthracene and benzidine. The compounds tested were either very efficient substrates or showed minimal activity as reducing substrates. Benzidine, 2,4-diaminoanisole and 2,5-diaminoanisole were excellent substrates providing nearly stoichiometric hydroperoxide reduction even at low enzyme concentrations. On the other hand, the five remaining compounds showed no activity as reducing substrates. Increases in enzyme and/or substrate concentration still did not produce any significant enzymatic activity with the poor substrates. The results of these investigations provide important information concerning the metabolic activation of these aromatic amines by PHS. There is evidence in the literature that some of these amines are metabolized by PHS to mutagenic and carcinogenic species. For the efficient reducing substrates this remains a reasonable suggestion. However, for the poor reducing substrates, alternative possibilities for the oxidizing agent must be considered. PMID- 3102099 TI - Modulation of monocrotaline-induced hepatic genotoxicity in rats. AB - Monocrotaline (MCT), a hepatotoxic/hepatocarcinogenic pyrrolizidine alkaloid (PA) induced DNA-DNA interstrand crosslinks in a dose-dependent manner through 30 mg/kg. Hepatic cytochrome P-450 has been shown to bioactivate MCT to pyrrole derivatives which are thought to be responsible for these genotoxic lesions. We have hypothesized these lesions to be related to the adverse hepatic actions of MCT and other PAs. Studies reported here investigated the effect of phenobarbital, a P-450 inducer, 2-dimethylaminoethyl-2,2-diphenylvalerate, a P 450 inhibitor and butylated hydroxyanisole, a dietary antioxidant, on hepatic DNA DNA interstrand cross-links induced by a single dose of MCT (15 mg/kg i.p.) administered to male Sprague-Dawley rats. DNA damage was assessed by alkaline elution. The effects of these pretreatment regimens on MCT-induced DNA-DNA interstrand cross-linking was qualitatively similar to their reported effects on the hepatotoxicity of MCT. The effects of these pretreatments on hepatic cytochrome P-450 content, hepatic non-protein sulfhydryl levels and hepatic glutathione S-transferase activities were similarly investigated in attempts to explain the observed effects on DNA cross-link induction. These data provide further support for the association between DNA damage and the adverse hepatic effects of MCT. PMID- 3102100 TI - Benzoyl peroxide promotes the formation of melanotic tumors in the skin of 7,12 dimethylbenz[a]anthracene-initiated Syrian golden hamsters. AB - A two-stage carcinogenesis experiment was performed in Syrian golden hamsters using a single intragastric initiation with 10 mg/kg body weight of 7,12 dimethylbenz[a]anthracene (DMBA) and repetitive topical promotion on the back skin with two different doses (80 and 160 mg, respectively) of benzoyl peroxide in 1 ml acetone. Benzoyl peroxide was administered three times per week over a period of 16 months. The treatment with benzoyl peroxide alone leads to both a generalized hyperpigmentation and skin scaling without formation of any tumors. DMBA initiation alone induces a moderate number of melanotic foci and a small number of palpable melanotic tumors. Both lesions are located in the dermis. Papillomas develop in the epithelia of the tongue, esophagus and especially of the forestomach but not, however, on the back skin. The combined treatment with DMBA and both doses of benzoyl peroxide drastically increases the incidence of dermal melanotic foci and at late stages also that of melanotic tumors. Therefore, in addition to its known ability to promote papilloma and carcinoma formation in the back skin of mice, benzoyl peroxide is also able to promote the formation of melanotic tumors in the dermis of hamsters. PMID- 3102101 TI - Regulation by calcium of arachidonic acid metabolism in the isolated perfused rabbit heart. AB - Activation of beta-adrenergic receptors with isoproterenol fails to stimulate prostaglandin synthesis in the isolated rabbit heart perfused with Ca2+-free Krebs-Henseleit buffer. This lack of response could be due to reduced isoproterenol-stimulated liberation of arachidonic acid, reduced cyclooxygenase activity during Ca2+-free perfusion, or both. To test these hypotheses, we have examined the effect of isoproterenol and exogenous arachidonic acid on prostaglandin output in hearts perfused with Ca2+-containing and nominally Ca2+ free Krebs-Henseleit buffer. In hearts prelabelled with [3H]arachidonic acid and perfused with nominally Ca2+-free buffer, the release of radioactivity following isoproterenol was about 90% less than when Ca2+ was included in the perfusion buffer. When exogenous arachidonic acid was administered to hearts perfused with Ca2+-depleted buffer, the output of both 6-keto-prostaglandin F1 alpha and prostaglandin E2 was about threefold greater than when Ca2+ was present in the perfusion medium. In the absence of Ca2+, the dose response curve for arachidonic acid-induced 6-keto-prostaglandin F1 alpha synthesis underwent a parallel shift to the left, with no change in maximal synthesis levels, and a tenfold reduction in the ED50 of arachidonic acid. The cyclooxygenase activities of cell-free homogenates prepared from hearts perfused with and without Ca2+ were not different from each other and were both insensitive to added Ca2+. Reduction of the Na+ concentration of the perfusion medium to 35 mM resulted in increases in arachidonic acid-induced 6-keto-prostaglandin F1 alpha less than those obtained during Ca2+-free perfusion, but greater than that observed during perfusion with normal Na+ (139 mM) and Ca2+ (2.5 mM). Arachidonic acid induced 6-keto prostaglandin F1 alpha output was inversely correlated with tissue Ca2+ but not Na+ content. These data suggest that in the absence of perfusate Ca2+, the availability of exogenous arachidonic acid to cyclooxygenase is increased, possibly by reduced incorporation into tissue phospholipids. PMID- 3102102 TI - [Naga peptide of rabbit periaqueductal gray (PAG) and its relationship to acupuncture analgesia]. PMID- 3102103 TI - [Influences of intranigral injection of kainic acid on electroacupuncture analgesia and morphine analgesia in the rabbits]. PMID- 3102104 TI - [The influence of acupuncture on nonspecific esterases in the hypothalamus]. PMID- 3102105 TI - [Involvement of GABA in acupuncture analgesia]. PMID- 3102106 TI - [Effect of electro-acupuncture on monophasic action potentials of the ischemic myocardium in rabbits]. PMID- 3102107 TI - [Electron microscopic observation on the effects of acupuncture in ultrastructures of acute ischemic myocardia]. PMID- 3102108 TI - [The relative specificity of the cortex-evoked response elicited by stimulation of acupoints and nonacupoints on the forelimb in cats]. PMID- 3102109 TI - [Investigation on cortical somatosensory evoked potentials during the advance of propagated sensation along channels]. PMID- 3102110 TI - [Observation of the relative specificity between the stimulated auricular point and propagated sensation along channel (PSC)]. PMID- 3102111 TI - [Recording of the gastroelectrogram (GEG) from the surface of the body]. PMID- 3102112 TI - Effects of electrical acupuncture of the neiguan area on the homeostasis of left ventricular performance. PMID- 3102113 TI - [Experimental study of the effect of electroacupuncture on rats with slow heart rate]. PMID- 3102114 TI - [Resetting of the baroreceptor reflex by electroacupuncture in conscious rabbits]. PMID- 3102115 TI - Effect of electroacupuncture on myocardial contractility in open-chest and anesthetized dogs with acute respiratory failure. PMID- 3102116 TI - [Effect of electroacupuncture on cardio-hemodynamics in dogs with acute respiratory failure (ARF)]. PMID- 3102117 TI - [Effect of acupuncture on the coronary collateral circulation of dogs suffering form experimental myocardial infarction]. PMID- 3102118 TI - [Effect of electro-acupuncture on the metabolism of oxygen during experimental cerebral infarction]. PMID- 3102119 TI - [Effect of electro-acupuncture on the cerebral volume of blood flow during experimental cerebral infarction]. PMID- 3102120 TI - Role of the preoptic-anterior hypothalamic area in the relationship between "neiguan" and the heart. PMID- 3102121 TI - Effect of electroacupuncture at "neiguan" on discharges of neurons in the preoptic-anterior hypothalamus. PMID- 3102122 TI - [Effect of electrical needling the "neiguan" point on the promotion of the recovery of acute myocardial ischemia in cats: analysis of afferent pathways]. PMID- 3102123 TI - [The effect of electroacupuncture on the visceral auricular point response in rabbits]. PMID- 3102125 TI - Percentile estimates of reference values for total protein and albumin in sera of premature infants (less than 37 weeks of gestation). AB - We measured the concentrations of total protein and albumin in sera of 281 well fed premature infants, gestational ages 22-36 weeks, and calculated reference values from the 10th to 90th percentiles. The mean serum albumin concentration (27.6 +/- 4.4 g/L, mean +/- SD) and total protein concentration (49.2 +/- 6.7 g/L) at a postnatal age of 14.5 days were lower than reference values for full term infants. We detected a significant positive correlation between albumin concentration and gestational age (r = 0.34, p less than 0.01) and total protein concentration and gestational age (r = 0.43, p less than 0.01). Even though albumin values were low, generalized edema was not present. We conclude that values for total protein and albumin in the preterm infant are lower than in the full-term infant but are an expected physiological response to premature birth. PMID- 3102124 TI - A method for serum C1q based on its hydroxyproline content. AB - The radial immunodiffusion assay overestimates the C1q in serum. Here we describe a convenient, accurate procedure for measuring C1q in 250 microL of dialyzed serum. This method is based on our previous findings that all C1q in serum precipitates with the euglobulin fraction and that all other serum proteins containing hydroxyproline are excluded from this fraction. Because C1q is 4.3% hydroxyproline, the concentration of C1q in serum can therefore be calculated from the hydroxyproline content of the euglobulin fraction. The procedure, all done in the same tube, consists of precipitating the euglobulin fraction, digesting it with HClO4, and converting hydroxyproline to the corresponding pyrrole, which is extracted with toluene and measured by absorbance at 560 nm. PMID- 3102126 TI - "Quantimetric" kappa:lambda ratio test. PMID- 3102128 TI - Schistosomiasis in a cystic teratoma of the ovary. AB - The authors report the case of an ovarian teratoma infected by the eggs of the trematode Schistosoma haematobium. In consideration of the rare observation, bearing a paradigmatic value, they briefly discuss the particular tropism that the parasite demonstrated towards some tumoral structures and they also outline the immunological mechanisms activated by the Schistosoma. PMID- 3102127 TI - Action of a prostaglandin synthetase inhibitor on IUD associated uterine bleeding. AB - The Authors treated twenty-eight women using IUD, who suffered from increased menstrual blood loss and pelvic pain, with a prostaglandin synthetase inhibitor, Suprofen, in an attempt to reduce their symptomatology, in a double blind crossover study. The drug produced an important reduction of the menstrual blood loss and pains. These observations suggest that prostaglandins are involved in the etiology of excessive menstrual blood loss and pains, and that prostaglandin inhibitors may be useful for reducing these symptoms. PMID- 3102129 TI - Pharyngeal diverticula. AB - A series of 73 hypopharyngeal (Zenker's) diverticula is reported and the choice of treatment and technique of excision are discussed. The problems of excision include operation on an infected site with limited access but few patients are unfit for the procedure. Preoperatively the sac should be packed and the oesophagus stented. The side of approach is unimportant as the condition is essentially midline. Cricopharyngeal myotomy appears to reduce the recurrence rate, possibly by improving coordination of pharyngeal contraction and upper oesophageal relaxation. The use of electrocoagulation is not recommended as 20% of patients require repeated general anaesthesia and the procedure fails in 13%. For all but the smallest pouches, excision is the treatment of choice. PMID- 3102130 TI - Lactase deficiency and lactose malabsorption. PMID- 3102131 TI - Cryptophthalmos-syndactyly syndrome without cryptophthalmos. PMID- 3102133 TI - Antigens of virulent and attenuated Rickettsia tsutsugamushi. AB - We studied the antigens present in L929 mouse fibroblast or rabbit testicular cells, which had been infected or not with a prototype strain of Rickettsia tsutsugamushi, the causal agent of scrub typhus, and its attenuated variant. Immunoblotting revealed four antigens, designated 1, 1a, 2 and 3, which appeared to be specifically associated with infection with this organism. Antigens 1 and 1a had similar mol. wt of about 60 kD and antigen 2 and 3 had mol. wts of 45 kD and 28 kD respectively. Whereas antigen 1a, 2 and 3 were common to infection with either the virulent or the attenuated strains of the organism, antigen 1 was only detected in cells infected with the virulent strain and was reactive only with the antiserum raised against cells infected with that strain. In addition, two antigens were also detected by crossed immunoelectrophoresis, one of which was similarly associated with infection with the virulent strain as antigen 1, while the other was common to infection with either of the strains. It seems that the antigenic cross reaction between the two strains may account, in part at least, for the protection of mice against infection with the virulent strain afforded by the attenuated strain, while the loss or modification of antigen 1 might be associated with attenuation of the organism with respect to its virulence to mice. PMID- 3102132 TI - Monoclonal anti-tuberculosis antibodies react with DNA, and monoclonal anti-DNA autoantibodies react with Mycobacterium tuberculosis. AB - Classical models of experimental autoimmune diseases, such as adjuvant arthritis entail the use of mycobacteria. Furthermore, BCG immunotherapy may be followed by arthritic symptoms. To test the infection-autoimmunity relationship of mycobacteria, we used monoclonal antibodies raised against M. tuberculosis and against DNA. Murine monoclonal anti-TB antibodies were found to react with ssDNA, dsDNA and other polynucleotides. Monoclonal anti-DNA autoantibodies derived from patients and mice with SLE bound to three glycolipids shared among all mycobacteria and derived from mycobacterial cell wall. Prior incubation of the antibodies with ssDNA and other polynucleotides or with glycolipid antigens inhibited binding. These results indicate that infecting mycobacteria share antigens with human tissue, thus accounting in part for the production of autoantibodies in mycobacterial infections. PMID- 3102135 TI - B lymphocyte activation by insoluble anti-mu antibodies in patients with systemic lupus erythematosus. AB - In order to study the capacity of anti-immunoglobulin (Ig) antibodies to induce proliferative responses in peripheral blood mononuclear cells (PBC) from patients with systemic lupus erythematosus (SLE), anti-mu coupled to Sepharose beads (anti mu) was used as a polyclonal activator. In 18 patients, a strong proliferative response was associated with inactive disease, and the response was lower in clinical active disease (P less than 0.02). An inverse correlation could also be observed in six patients who were studied longitudinally (P less than 0.01). These results indicate that anti-mu responsiveness is closely related to disease activity in SLE. In addition, sequential data obtained from two patients during an early stage of clinical deterioration suggest that a low anti-mu response might be an early indicator of a clinical relapse. In the patients investigated, the anti-mu response was not correlated with the response to pokeweed mitogen (PWM), or with the quantity of B cells. When T cell depleted cell fractions were studied, marked increases in the proliferative responses to anti-mu were observed in some patients. These studies suggest that the response to anti-mu might be modified by T cells to a variable extent in patients with SLE. PMID- 3102134 TI - Induction of interleukin 2 receptors on immature human thymocytes and co expression of T3 and T6 antigens. AB - We have recently demonstrated that human thymocytes can be induced to express interleukin 2 (IL-2) receptors and to synthesize IL-2. The present study shows that relatively immature T6+ human thymocytes as well as the more mature T3+ thymocytes could be induced to express functional IL-2 receptors when activated with either Concanavalin A (Con A), Con A and 12-O-tetradecanoylphorbol 13 acetate (TPA) or IL-2 in combination with Con A or TPA. The phenotype of the common, immature thymocyte was identified by the binding of either fluorescein isothiocyanate (FITC)- or phycoerythrin (PE)-conjugated monoclonal anti-T6 (OKT 6) antibody and of mature thymocytes by the binding of monoclonal anti-T3 (OKT 3) antibody. We also observed that the expression of the T3 antigen on thymocytes, freshly isolated from thymic specimens obtained in the course of cardiac surgery of infants and children, was greater than 40% in 14 of 18 donors and that thymocytes co-expressed the T3 and the T6 antigen as determined by dual colour cytofluorometry. In thymocytes activated in vitro the expression of IL-2 receptors, determined by dual colour cytofluorometry with the PE-conjugated monoclonal anti-human IL-2 receptor antibody (PE anti-IL-2 R), was detected by the second day of induction in both immature T6+ and mature T3+ thymocytes. T6+ thymocytes proliferated in response to IL-2 and persisted in cultures for the duration of the study (18 days) and continued to express IL-2 receptors. PMID- 3102136 TI - Cognitive function in hemodialysis patients. AB - Cognitive function was assessed in two groups of hemodialysis patients exposed to relatively low concentrations of aluminum in source water used to manufacture dialysate. One group of patients (long-term group) had been on dialysis for 5 years or more, the other (short-term group) for less than 5 years. Group comparison showed no significant differences of any cognitive measure. However, calculating an index of deterioration based on the discrepancy between current reading skills and current performance on the Wechsler Adult Intelligence Scale, five patients in the long-term group and two in the short-term group could be identified as functioning below their predicted premorbid optimum level. There was no correlation between cumulative exposure to water-born aluminum and any of the measures of cognitive function in either of the groups. There was a statistically significant negative correlation between the cumulative amount of aluminum prescribed to be taken orally and performance on cognitive tests in the long-term group. This observation strengthens the case for minimizing the prescription of aluminum-containing gut phosphate binders. PMID- 3102137 TI - Low red cell arachidonic acid in hemolytic uremic syndrome. AB - A defect in prostacyclin generation has been proposed in hemolytic uremic syndrome (HUS): prostacyclin is formed from arachidonic acid derived from phospholipid and low levels of some phospholipids have been described in HUS cell membranes. Therefore fatty acid content of the red blood cell membranes of 8 children with HUS was compared with 32 children with other renal disease, with 33 patients with non-renal disease and with 8 normal adults. Children with HUS consistently had lower proportions of arachidonic acid (2.7-8.4%) than all other groups (10.1-18.8%) and the mean arachidonic acid level in HUS was very significantly reduced (p less than 0.0001). These findings suggest a reduced availability of arachidonic acid for prostaglandin synthesis in HUS and are consistent with the proposition that arachidonic acid is lost through peroxidative change. PMID- 3102138 TI - Acute and chronic pulmonary thromboembolism: current perspectives. Part VII: Current trends and newer developments. PMID- 3102139 TI - Results of treatment of fracture-dislocations of the elbow. AB - Twenty-four patients with ulnohumeral dislocation associated with radial head fracture were studied two to 35 years after injury. On the basis of an objective functional grading score that included elements of pain, motion, strength, and stability, results were excellent in three (12%), good in 15 (62%), and fair in six (25%). The best results were obtained in patients with Mason Type 2 injuries treated by closed reduction without fracture excision and with early complete radial head excision for a Type 3 fracture. Late instability was not observed in any of the 24 patients. Prolonged immobilization (greater than four weeks) was associated with poor results. Ectopic ossification occurred in only one patient who had surgical treatment at eight days after injury; the grading score was only fair. These observations demonstrate that the injury should be treated with early reduction of the ulnohumeral joint and treatment of the radial head fracture according to its type. Immobilization for more than four weeks should be avoided. The prognosis is better than what has been thought previously. PMID- 3102140 TI - Evaluation of the utility of indium-111 oxine platelet imaging in renal transplant patients on cyclosporine. AB - Twenty five In-111 oxine platelet imaging procedures were performed in 21 renal transplant patients to assess the value of this study for diagnosis of renal transplant rejection in recipients receiving cyclosporine (CYS) for immunosuppression. Fourteen biopsies were performed, and an extensive, in-depth review of the clinical progress of each patient was obtained. There was no ideal "gold standard" to which our imaging results could be compared, but we used a combination of biopsy findings, clinical impressions, and changes in renal function after pulsing with steroids and/or decreasing CYS dosage as the basis for our diagnoses. We were unable to distinguish between renal rejection and CYS toxicity using platelet imaging. The sensitivity of the platelet procedure for diagnosing rejection or CYS toxicity was 100%. The specificity for rejection or CYS toxicity was only 76.5%. In view of the inability of this test to distinguish between rejection and CYS toxicity, its rather low specificity, and its relatively high cost, it is not a particularly helpful study for the diagnosis of renal transplant rejection in patients on CYS. PMID- 3102141 TI - Artifactual focal lung activity with indium-111 labeled leukocytes. A technical pitfall. AB - A case of artifactual multifocal lung activity presumably due to emboli of In-111 labeled leukocytes is described. These may have been caused by infusion through an intravenous line containing glucose, or by a minute amount of blood clotted in the needle. When administration through an existing intravenous line is necessary, flushing with saline before and after cell infusion is recommended to avoid this potential pitfall. A fresh needle also should be used for each venipuncture attempt. PMID- 3102142 TI - Uptake of bone scanning agent in neurofibromatosis. PMID- 3102146 TI - Diabetic ketoacidosis associated with thrombotic thrombocytopenic purpura. PMID- 3102145 TI - Orbital neurofibromatosis. AB - The origin of neurofibromatosis (the neuroectoderm, the mesectoderm, or both primordia?) is not known. The protean manifestations of the disease cannot be explained, and classification of the various forms of orbital neurofibromatosis on the basis of specific neural involvement has never been attempted. Further studies of the pathogenesis are therefore urgently needed. Differentiation between types of orbital tumors may benefit from advanced computer scanning and nuclear magnetic resonance techniques. The results of surgical treatment, although much improved in recent years, are still unsatisfactory. Concentration of patients with neurofibromatosis in specialized centers is therefore indicated. PMID- 3102143 TI - Clinical pharmacokinetics of glyceryl trinitrate following the use of systemic and topical preparations. AB - Glyceryl trinitrate has been used for more than a century for the treatment of angina pectoris and, more recently, for the treatment of congestive heart failure. The introduction of transdermal delivery systems has renewed the controversy regarding the efficacy of the drug, mainly in the light of the development of tolerance. With concentrations of the order of 1 microgram/L or less, the measurement of glyceryl trinitrate in plasma is not easy: gas chromatography with electron capture detection has been used widely but recently gas chromatography-mass spectrometry has provided satisfactory results. Assay problems are most likely to be responsible for some of the unexpected results reported. Further factors which may confound the results of the study of plasma concentrations are the rapid metabolism of glyceryl trinitrate in blood in vitro, adsorption to containers and infusion sets, and the uptake and/or metabolism in vessel walls. From the intravenous infusion data, the large interindividual variability in plasma concentrations of glyceryl trinitrate is apparent. The plasma half-life is about 2 to 3 minutes; plasma clearance values reported vary from 216 to 3270 L/h, indicating extensive non-hepatic metabolism. With transdermal administration, mainly with the transdermal controlled delivery systems, plasma concentrations of glyceryl trinitrate appear to be maintained for up to 24 hours, with large interindividual variations. Despite the ability to maintain, for example with the transdermal delivery systems, relatively constant concentrations of glyceryl trinitrate, it has not been possible to find a relationship between plasma concentrations and pharmacological or clinical effects. This is in part due to the attenuation of the effects with time; from the available data it is clear that this attenuation occurs at a pharmacodynamic level (reflex adaptation and tolerance) and not at the pharmacokinetic level. PMID- 3102147 TI - Bone scintigraphy in oncology: an update with emphasis on efficacy and cost effectiveness. AB - Bone scintigraphy has been helpful to oncologists in the initial evaluation and diagnostic follow-up of patients with primary and secondary neoplasms. This review discusses this way of bone imaging with respect to the choice of the bone seeking radiopharmaceutical and puts emphasis on its diagnostic yield and cost effectiveness in various malignant diseases. PMID- 3102144 TI - A kinetic analysis of fibrinogenolysis during plasminogen activator therapy. AB - A mathematic model of the systemic fibrinogenolysis that accompanies coronary thrombolysis with recombinant tissue plasminogen activator (rt-PA) has been devised. The kinetic parameters of the model were estimated by nonlinear regression analysis with data from a clinical trial of rt-PA. The plasma elimination rate constant for rt-PA was estimated to be 10.0 hr-1, the second order catalytic rate constant for the in vivo rt-PA-mediated conversion of plasminogen to plasmin 0.0078 (microgram rt-PA/kg body weight)-1 hr-1, the plasma elimination rate constant for plasmin 2.33 hr-1, and the second-order catalytic rate constant for the in vivo plasmin-catalyzed degradation of fibrinogen 0.466 (mg plasmin/dl)-1 hr-1. Computer simulation studies based on these parameter estimates show that the magnitude of fibrinogenolysis induced by rt-PA is related to the dose in a curvilinear fashion, showing diminishing increments in the effect at increasing doses. The degree of fibrinogenolysis induced by rt-PA administration is nearly independent of the dosing schedule. PMID- 3102148 TI - Serial evaluation of lymphocyte function in bone marrow-grafted patients. AB - Deficiencies in both cellular and humoral immunity follow human bone marrow transplantation, predisposing recipients to life-threatening infections. Peripheral blood mononuclear cells (cells of donor marrow origin) from nine patients were collected serially at 3-month intervals during the first year post transplant and evaluated for proliferation and lymphokine (gamma interferon and interleukin-2) production in vitro. Cultures of patient cells or those of normal adult volunteers were stimulated by phytohemagglutinin (PHA) in vitro, and lymphocyte blastogenesis was assayed by tritiated thymidine uptake on day 2. PHA blastogenesis for peripheral blood mononuclear cell cultures from patients post bone marrow transplant achieved normal levels 3-6 months post transplant. Supernatants produced by cells from marrow recipients (less than 12 months post transplant) had lower-than-normal IFN-gamma activity and decreased IL-2 activity. Two patients with acute graft-vs-host disease (GVHD) had persistently depressed PHA blastogenesis, IFN-gamma production, and IL-2 production at 12 months post transplant. PMID- 3102149 TI - Augmentation of natural immunity and correlation with tumor response in melanoma patients treated with human lymphoblastoid interferon. AB - Thirty-two melanoma patients treated with lymphoblastoid alpha interferon (Wellferon) were studied for augmentation of five putative parameters of natural immunity including natural killing (NK), antibody-dependent cellular cytotoxicity (ADCC), cell-mediated inhibition of growth in culture of a murine tumor (GIA), and the size of the OKTIO+ and Leu 7+ subpopulations of peripheral blood mononuclear cells (OKTIO and Leu7). This study confirms and extends our previous conclusions that interferon increases GIA and OKTIO. The increases occurred at 24 hr after interferon, both early and late in the course of treatment, and were dose dependent. NK, ADCC, and Leu7 were activated in many patients individually and mean values for NK and Leu7 were increased in the population as a whole. Two patients with complete remission showed dramatically increased natural immunity by the parameters studied, but the pattern of increase was very different for each patient. The current study of lymphoblastoid alpha interferon demonstrates the immunomodulatory potential of interferon given to melanoma patients, but it fails to support the hypothesis that augmentation of these parameters of natural immunity by interferon may result in tumor responses. PMID- 3102151 TI - Cromolyn's effects on the immune system. PMID- 3102150 TI - Early activation marker expression to detect impaired proliferative responses to pokeweed mitogen and tetanus toxoid: studies in patients with AIDS and related disorders. AB - We tested the premise that measurement of interleukin 2 receptor (IL2R) and transferrin receptor (TR) can be used to assess proliferative responses to pokeweed mitogen (PWM) and tetanus toxoid (TT). Our study group consisted of patients with Human Immunodeficiency Virus (HIV) infection, including patients with acquired immunodeficiency syndrome (AIDS, n = 10), AIDS-related complex (n = 14), lymphadenopathy syndrome (n = 7), or homosexual men seropositive for HIV (n = 6). Controls were 40 healthy seronegative blood donors. IL2R and TR expression by stimulated mononuclear cells were assessed using specific monoclonal antibodies and flow cytometry, and results were analyzed using the 3H-thymidine assay for DNA synthesis as a standard for comparisons. For identifying low PWM responses, both the IL2R+ cell percent and the IL2R+ cell number (no.) per lymphocyte trigger region (a relative measure of IL2R+ cell no. per culture) on day 3 (72 h) were sensitive (greater than 90%) and specific (80%); day 3 TR+ cell no. was also sensitive (92%) and specific (100%). For detecting low TT-induced responses, day 7 IL2R+ cell no. proved the most sensitive (100%) and specific (78%) parameter. These findings indicate that cytofluorometric analysis of IL2R and/or TR expression is a reliable method for detecting impaired proliferative responses to PWM and TT in these patients. Such a method offers an attractive alternative to the regulatory and disposal problems associated with radioactivity in the conventional DNA synthesis assay, as well as providing insight to the mechanism(s) responsible for impaired proliferation. PMID- 3102152 TI - Inter-sterno-costo-clavicular ossification. AB - The clinical and radiological features of four patients with inter-sterno-costo clavicular ossification are described. The process was associated with established seronegative spondyloarthropathy in three cases of whom four had long standing psoriasis, the other having ankylosing spondylitis. In the fourth case no associated arthropathy was present. A review of the literature is presented. PMID- 3102154 TI - Hyperosmolar, hyperglycemic, nonketotic coma in a patient receiving home total parenteral nutrient therapy. AB - A patient who developed hyperosmolar, hyperglycemic, nonketotic coma (HHNC) while receiving home total parenteral nutrient (TPN) therapy is described, and the etiology, clinical features, and treatment of HHNC are reviewed. A 51-year-old black man diagnosed as having Dukes' stage D signet-cell carcinoma of the rectum was discharged on home TPN therapy after a prolonged hospital course and the persistence of a gastrointestinal fistula. Seventeen days after discharge, the patient developed polyuria, became febrile, and lost mental acuity. Upon hospitalization, the patient's physical condition and laboratory values were consistent with the diagnosis of HHNC. The patient was treated with intravenous fluids and small quantities of insulin. The patient's home records indicated that he had lost large volumes of fluid through his fistula, resulting in a net negative fluid balance. The patient's records also indicated that he had had mild glycosuria with a normal urine output at home. This normal urine output despite a body-fluid deficit could be explained by osmotic diuresis related to either glucose or urea. Hypotonic fluid loss resulting from fistula output and osmotic diuresis may have led to this patient's hypertonic state and critical illness. The patient died on hospital day 11 as a result of widely disseminated cancer. HHNC arises most often as a complication of non-insulin-dependent diabetes. It is also a major complication resulting from hypertonicity related to glucose intolerance or other conditions that can occur in patients receiving TPN therapy. The underlying cause of the hyperosmolar state appears to be dehydration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102153 TI - Dissociation between circulating concentrations of immunoreactive growth hormone releasing factor and growth hormone in normal human subjects. AB - Using a highly specific radioimmunoassay we have measured immunoreactive human growth hormone releasing factor (ir-hGRF) concentrations in the peripheral circulation of a total of 12 normal subjects. Neither insulin-induced hypoglycaemia, intravenous arginine nor oral carbohydrate caused any change in venous plasma ir-hGRF concentrations, despite the expected stimulation and suppression respectively of growth hormone secretion. Growth hormone secretion was not increased by oral fat or protein but each of these two foods stimulated ir-hGRF concentrations two- to four-fold. Spontaneous pulses of growth hormone secretion on control days were unaccompanied by any increase in plasma ir-hGRF. The dissociation between peripheral circulating ir-hGRF and growth hormone responses demonstrated under different circumstances suggests that an important source of human growth hormone releasing factor lies outside the hypothalamus and that secretion from this source is unconnected with the normal control of pituitary growth hormone secretion. PMID- 3102155 TI - [Preliminary clinical study on the treatment of amyotrophic lateral sclerosis with TRH]. PMID- 3102156 TI - Determination of synergy by two methods with eight antimicrobial combinations against tobramycin-susceptible and tobramycin-resistant strains of Pseudomonas. AB - Eleven strains of tobramycin-susceptible Pseudomonas aeruginosa, 12 strains of tobramycin-resistant P. aeruginosa, and 11 strains of P. maltophilia were tested against tobramycin in combination with azlocillin, piperacillin, ceftazidime, and imipenem and against colistin in combination with azlocillin, piperacillin, ceftazidime, and imipenem by microdilution checkerboard and time-kill curve techniques. Synergistic or additive effects were demonstrated in the tobramycin ceftazidime combination against tobramycin-resistant strains of P. aeruginosa and P. maltophilia, and with all tobramycin combinations against tobramycin susceptible strains of P. aeruginosa using the checkerboard technique. Synergistic and additive effects were seen with the time-kill curve technique with colistin-ceftazidime, colistin-imipenem, and tobramycin-piperacillin combinations against tobramycin-susceptible P. aeruginosa and in the colistin ceftazidime combination against tobramycin-resistant P. aeruginosa. Fractional inhibitory concentrations (FIC) and fractional bactericidal concentrations (FBC) from checkerboard studies were compared to the time-kill curve results and vice versa. The overall agreement with FIC was 39.4% and 40.9% and agreement with FBC was 40.9% and 43.9%. This limited study illustrates the lack of agreement between these techniques in demonstrating antimicrobial synergy against pseudomonads. PMID- 3102157 TI - Mixed morphotype susceptibility testing of Pseudomonas aeruginosa from patients with cystic fibrosis. AB - Disk diffusion antibiograms were determined for mixtures of Pseudomonas aeruginosa morphotypes isolated from the sputum of patients with cystic fibrosis (CF). The results were compared with the predicted susceptibility patterns derived from the antibiograms of individual morphotypes within the mixture. Fifty separate cultures, each yielding two, three, or four distinct morphotypes of Pseudomonas aeruginosa were evaluated. Overall, the correlation between observed and predicted results was 92.2% with only 2.9% of all observations leading to major disagreements in susceptibility. These data suggest that mixed morphotype susceptibility is potentially a useful method to monitor the collective resistance of colonizing strains of Pseudomonas aeruginosa from the respiratory tract of patients with CF. PMID- 3102158 TI - Immunoelectron microscopic localization of collagenase inhibitor in bovine dentin. AB - The localization of collagenase inhibitor in bovine dentin was investigated by immunohistochemistry and immunoelectron microscopy using a specific rabbit antiserum raised against the inhibitor purified from culture medium of bovine unerupted third molar pulps. Immunoreactive collagenase inhibitor was mainly localized as an amorphous or granular accumulation along the wall of dentinal tubules in decalcified bovine dentin. A part of the immunoreactive inhibitor appeared as two periodic bands on the collagen fibrils surrounding the dentinal tubules. Those two, a major and a minor band, corresponded to D-periodic fibril bands V-VII and I, respectively. As those two bands are located on both borders between overlap and hole zones of the collagen fibril, C- and N-terminal non helical peptides and eight regions which are nD (n = 1-4) apart from each non helical peptide along the triple helix are all equally possible binding sites of the collagenase inhibitor on the collagen molecule. It is interesting that the major band is located not exactly at, but fairly close to, the locus of collagenolytic cleavage, which lies between D-periodic fibril bands IV and V. PMID- 3102159 TI - The effects of tissue pretreatment and pepsin levels on the isolation of collagens from human placenta. AB - A comparative study has been undertaken to ascertain the effects of different tissue pretreatment procedures on the recovery of the major genetic types of collagen from human placenta. Essentially the same recovery of types I, III, IV and V collagen was obtained from placenta which was directly processed, from placenta which was stored at -70 degrees C after washing, and from dried acetone extracts of this tissue. Each collagen type isolated from the treated tissue preparations displayed properties consistent with those exhibited by its counterpart obtained from fresh tissue which was directly processed. Furthermore, it was observed that while the amount of types I and III collagen recovered was directly proportional to the level of pepsin employed, the recovery of types IV and V collagen was inversely related to this isolation parameter. These results establish that human placenta can be either stored frozen or as a dry acetone extract without affecting either the yield or the profile of the different genetic types of collagen recovered and that the amounts of different genetic types of collagen recovered can be modulated by the amount of pepsin employed in the isolation. PMID- 3102160 TI - Composition and labeling by [3H]glycerol and [3H]serine of phospholipids of the chicken retina and optic tectum. AB - The content and fatty acid composition of phospholipids and the in vivo labeling of lipids by [3H]glycerol and [3H]serine was studied in the retina and the optic tectum of young chickens. The tectum had a higher content of phospholipids and a significantly lower ratio of choline (CGP) to ethanolamine (EGP) glycerophospholipids than the retina. Lipids of the chicken optic system were characterized by a high proportion of polyenoic fatty acids of the n-6 series compared to other species. Intravitreally injected [3H]glycerol was incorporated into all glycerol-containing lipids of the retina, especially in CGP and EGP. Most of the label from [3H]serine was found in serine glycerophospholipids (SGP). The time-dependent distribution of both precursors among retinal lipids was consistent with de novo synthesis as well as metabolic interconversions of lipids. Thus, [3H] from serine also appeared in EGP and CGP, indicating the presence and activity of SGP decarboxylase and EGP-n-methyl transferase. Lipids labeled with both precursors in retina were subsequently found in the tectum, via axoplasmic transport. Even though different lipid classes were labelled by each precursor the proportion of lipids transported to the tectum was similar in both cases (about 1% of the label present in retina). PMID- 3102161 TI - Evaluation of a new triphasic oral contraceptive in private practice. AB - We evaluated the clinical and metabolic effects of a new triphasic regimen developed in the continuing attempt to reduce the dose of estrogen and progestogen in oral contraceptives. A combination of ethinyl estradiol (EE) and levonorgestrel (LNg) was used (six tablets with 30 micrograms EE + 50 micrograms LNg, five tablets with 40 micrograms EE + 75 micrograms LNg, and 10 tablets with 30 micrograms EE + 125 micrograms LNg), also known as Triphasil (Wyeth). In a private practice, 409 subjects participated in 7,286 treatment cycles. Three pregnancies occurred, all due to subject failure. Menstrual regulation was excellent and the incidence of side effects extremely low. Withdrawals from the study for possibly drug-related medical reasons totaled 9.0% through 56 cycles of treatment. Metabolic changes also were evaluated in 14 of these women over a 6 month period. The only statistically significant increase in carbohydrate values occurred at 6 months. The mean glucose level at 30 minutes of the oral glucose tolerance test was above the baseline mean value, but serum insulin levels showed no statistically significant deviation. Lipid values presented are total lipids, total cholesterol, triglycerides, alpha-, beta-, and pre-beta-lipoproteins, and high density and low density lipoprotein cholesterol. There was no statistically significant difference between the mean values at baseline and those during treatment for any lipid variable. These results indicate that this triphasic oral contraceptive has a high degree of efficacy, a low incidence of side effects, excellent cycle control, and high subject compliance, and would seem to indicate a minimal influence on the metabolism of lipids and carbohydrates in the small number of subjects studied. PMID- 3102162 TI - The effect of deliberate omission of Trinordiol or Microgynon on the hypothalamo pituitary-ovarian axis. AB - The effect of deliberate omission of a phased formulation pill, Trinordiol (ethinyl estradiol 30 micrograms + levonorgestrel 50 micrograms: 6 tablets; ethinyl estradiol 40 micrograms + levonorgestrel 75 micrograms: 5 tablets; ethinyl estradiol 30 micrograms + levonorgestrel 125 micrograms: 10 tablets) or a low-dose, combined, oral contraceptive pill, Microgynon (ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms: 21 tablets) on the hypothalamo pituitary-ovarian axis were studied. Thirty-six women were recruited to the study and divided equally between the two types of pill. Medication was begun on the 8th pill-free day of the cycle and continued for 7 days (Group 1), 14 days (Group 2) or 21 days (Group 3). Levels of FSH, LH, estradiol (E2) and progesterone (P) were measured in plasma on alternate days during the final week of pill therapy, and daily for the 7 days after stopping the pill. For the first 2 weeks of pill therapy, follicular activity, as judged by plasma levels of E2, was greater in women taking Trinordiol than in those taking Microgynon, but was similar in both groups by the third week of pill treatment. Five women taking Trinordiol (2 in Group 1 and 3 in Group 2) had plasma levels of E2 in excess of 500 pmol/l whilst taking the pills, and only 1 patient achieved this degree of follicular activity after stopping the tablets. One woman who had taken 7 days of Trinordiol (Group 1) showed a rise of plasma levels of P to 6.8 nmol/l, but luteinization did not occur in any of the remaining 35 women who took Trinordiol or Microgynon. These findings suggest that follicular activity is less completely suppressed by Trinordiol than Microgynon, at least in the first 2 weeks of pill therapy, but that normal ovulation is still a rare event in the week after cessation of either of these pills, even if only 7 days of medication have been taken. PMID- 3102163 TI - Ventilation and pulmonary mechanics during high-frequency oscillation of immature lungs at birth. AB - Ventilation was initiated and maintained by high-frequency oscillation (HFO) in nine immature lambs not expected to survive for more than a few minutes out of the uterus. They were delivered to HFO (18 to 20 Hz) and ventilated only with air at the setting that yielded optimal blood gases and pH. Once removed from HFO, cardiorespiratory arrest occurred within minutes despite the return of previously inhibited natural inspiratory efforts. At autopsy, the lungs were liquid-filled (i.e., fetal). Thus, HFO had maintained viability without promoting either lung stability or fetal pulmonary fluid (FPF) absorption. Additional experiments on excised immature lungs showed that aeration is determined by distending pressure, which is regulated by the flow through the oscillator circuit and monitored most accurately as transpulmonary pressure (TPP). Once air-entry has begun, alveolar recruitment and negative compliance establish the limits of tolerable lung expansion via TPP. Within these limits, the immature lung can be ventilated effectively with air. However, since these lungs do not produce intrapulmonary foam, lung stability and FPF absorption are not effected. Complications of HFO (including pneumothorax, decreased arterial pressure and heart rate, and metabolic acidemia) can be related to overdistention of the lungs. PMID- 3102164 TI - A computer simulation program to facilitate budgeting and staffing decisions in an intensive care unit. AB - ICUs have unique problems in choosing their best staffing levels for direct patient care because each unit's total patient needs per shift, quantitated in acuity points, vary widely. We devised a computer program to simulate our 12-bed medical/cardiac ICU workload and staffing system. Nursing staffing policies, costs, and availabilities, and a table of past patient acuities per shift were input; total overstaffing, understaffing, and cost per year for full-time nursing equivalents (FTEs) for direct patient care were output for different staffing levels. Using the model, we considered financial concerns, quality of care issues, and staff working preferences and determined that our best staffing level would be based on 5.5 direct FTEs per shift. The stimulation analysis is straightforward, flexible, adaptable, and easy to update and use. PMID- 3102165 TI - Clinical characteristics and resource utilization of ICU patients: implications for organization of intensive care. AB - We reviewed the clinical characteristics and resource utilization of 391 medical (M) and 315 surgical (S) ICU patients. In general, MICU patients had more physiologic derangement, as determined by the admission, maximal, and average acute physiology scores (APS). SICU patients had more frequent therapeutic interventions as measured by admission, maximal, and average therapeutic intervention scoring system values. Notably, 40% of MICU and 30% of SICU patients never received any active interventions and were admitted strictly for monitoring purposes. Patients on admission with APS less than or equal to 10 had markedly shorter ICU stays, with almost 50% less treatment than patients with APS over 10. Fifty-six percent of patients with APS less than or equal to 10 did not require any active intervention. In contrast, 83% of patients with APS greater than 10 had considerable intensive interventions. These patients required mechanical ventilation, invasive monitoring, and vasoactive drugs more than twice as often as patients with lower APS scores. Consideration should be given, therefore, to the organization of ICUs according to the patient's severity of illness. PMID- 3102166 TI - Nonrebreathing valve competence. PMID- 3102167 TI - A comparison of the new topical antibiotic mupirocin ('Bactroban') with oral antibiotics in the treatment of skin infections in general practice. AB - A trial was carried out in general practice in 200 patients presenting with skin infections to compare topical antibiotic treatment with mupirocin ointment with orally administered flucloxacillin or erythromycin. Patients were assigned at random to receive 4 to 10 days' treatment with either mupirocin applied 3-times daily or one of the oral antibiotics in the dosage normally used by the general practitioner for skin infections. The majority of infections were impetigo and infected wounds/lacerations; the main organisms isolated initially from 127 of the patients were either Staphylococcus aureus or beta-haemolytic Group A streptococci. Clinical response to mupirocin ointment (86% cured, 13% improved) was significantly better than that seen with erythromycin (47% cured, 26% improved) and similar to that with flucloxacillin (76% cured, 23% improved). Treatment outcome was not related to treatment duration with either the topical or oral preparations. Post-treatment samples from 76 patients showed that in the mupirocin group all the pathogens originally isolated were eliminated, including Gram-negative organisms. PMID- 3102168 TI - Effect of dietary cyclopropene fatty acids on the amino acid uptake of the rainbow trout (Salmo gairdneri). AB - The rate of uptake of 3H-lysine in rainbow trout on 50 ppm dietary cyclopropene fatty acid (CPFA) was not significantly different from that of the control group. However, at 300 ppm CPFA treatment, the uptake of 3H-lysine was significantly lower than those in control or 50 ppm fed fish. Reduced ATP formation resulting from abnormal mitochondria may be responsible. PMID- 3102169 TI - The gene for galactosyltransferase maps to mouse chromosome 4. AB - The chromosomal localization of the gene for UDP-galactosyltransferase (glycoprotein 4-B-galactosyltransferase, EC 2.4.1.38) has been determined to be on mouse chromosome 4 by the use of mouse X hamster somatic cell hybrids. It has been proposed that galactosyltransferase is associated with the mouse T/t complex which has been localized to mouse chromosome 17. These results show that galactosyltransferase is not encoded within the T/t complex. PMID- 3102170 TI - Carbon dioxide excretion via bronchopleural fistulas in adult respiratory distress syndrome. AB - Expired gas and gas leaked via thoracostomy tubes was collected in nine patients with the adult respiratory distress syndrome (ARDS) and bronchopleural fistulas. Mean minute ventilation in the group was 23.9 +/- 7.5 L/min with 31 +/- 23 percent of the gas escaping via the leak. Carbon dioxide was present in the leaked gas in every patient, with the fraction of CO2 excreted via the leak highly correlated with the fraction of minute ventilation exiting via the leak (r = 0.86, p less than 0.005). Mean concentration of CO2 in leaked gas was 1.3 +/- 0.5 percent. We conclude that some of the gas leaked via a bronchopleural fistula in such patients participated in gas exchange. PMID- 3102171 TI - DRG payment for long-term ventilator patients. Implications and recommendations. AB - Much concern has been expressed about the Medicare Prospective Payment System's impact on access to care. In this study, we examine the financial impact of diagnosis-related group (DRG) payment for chronic ventilator-dependent Medicare patients. During a one-year period, payment for 95 Medicare patients who received a minimum of three days of continuous ventilator treatment and who spent no time in surgical intensive care at Rush-Presbyterian-St. Luke's Medical Center, was calculated to be $2.2 million below costs, representing an average loss per discharge of $23,129. Patients stayed an average of 26.6 days, of which 14.2 days were spent on a ventilator. We conclude that the results suggest a financial bias against chronic ventilator-dependent patients exists in the DRG system which could present access problems. We recommend three approaches to recognizing the cost of care for such patients in the DRG payment system and encourage those in public policy-making positions to use our results as the basis for a larger scale analysis of the impact of Medicare DRG payment on chronic ventilator-dependent patients. PMID- 3102172 TI - The financial impact of Medicare diagnosis-related groups. Effect upon hospitals receiving cardiac patients referred for tertiary care. AB - To evaluate the financial effects of diagnosis-related groups, we compared 128 Medicare and 183 non-Medicare cardiac patients aeromedically evacuated to a major referral center for critical care. A significant difference (p less than 0.05) was found between Medicare patients vs non-Medicare patients for age (71 +/- 7 vs 51 +/- 9 years) and mortality (13 percent vs 6 percent). No significant difference was found for admissions to the intensive care unit (95 percent vs 95 percent), mean length of stay in intensive care (4.7 +/- 5.3 vs 3.9 +/- 5.4 days), mean length of hospitalization (9.6 +/- 7.5 vs 7.9 +/- 7.0 days), mean number of International Classification Diagnoses (ICD-9) surgical operations (0.8 +/- 1.3 vs 0.6 +/- 1.2), and mean number of ICD procedures (3.0 +/- 2.3 vs 3.3 +/ 2.1). The average cost of care ($13,427 +/- $12,700 per patient) for Medicare patients was higher but not statistically different from non-Medicare patients ($10,474 +/- $10,114 per patient). Prior cost-based Medicare payments ($10,594 +/ $9,861 per patient) have been significantly (p less than 0.01) reduced by 24 percent under the Medicare diagnosis-related group (DRG) prospective payment system ($8,024 +/- $4,824). The DRG payments are significantly less than (p less than 0.001) and provide only 60 percent of the true hospital cost required to care for Medicare cardiac patients referred for tertiary care ($13,427 +/- $12,700 per patient). A Medicare DRG system adopted by third-party payers would reduce present hospital revenues from $9,524 +/- $8,422 per patient to $7,968 +/- $4,800 per patient and would provide only 68 percent of the cost required in the care of all cardiac patients referred for tertiary care ($11,690 +/- $11,344). The results of this study indicate that hospitals that receive large numbers of seriously ill cardiac patients, especially Medicare patients, referred for critical care are at a significant financial disadvantage under the Medicare DRG system. Future economic pressures may prohibit critical care treatment centers from accepting large numbers of cardiac patients referred for intensive care and reimbursed under the current Medicare DRG payment policy. PMID- 3102173 TI - Financial implications of prolonged ventilator care of Medicare patients under the prospective payment system. A multicenter study. PMID- 3102175 TI - Solid state fermentation of swine manures. AB - A kinetic model for the solid state fermentation of swine manures under both aerobic and anaerobic conditions have been proposed. The rate of CO2 production is used as an indicator of the degree of stabilization of swine manures. Analysis of available experimental data suggests that the initial rate of stabilization, as measured by the product of the reaction constant and the initial activity of bacteria, increases with temperature and correlates with the initial moisture content of swine manures. The rate of deactivation of bacteria, as reflected by the deactivation rate constant, is relatively constant for low and medium temperatures (25-35 degrees C) and is fast for higher temperature (45 degrees C). The optimum operating scheme should adopt a medium high temperature (35 degrees C) and an appropriate amount of initial moisture. PMID- 3102174 TI - Phagocytic cell-derived inflammatory mediators and lung disease. PMID- 3102176 TI - Complement pathway activity in the opsonization of mutant strains of Salmonella typhimurium. AB - Two separate complement pathway activities and their interaction in the opsonization of mutant strains of Salmonella typhimurium by human neutrophils were investigated in 1% and 10% sera. In the absence of antibody, all mutant strains of S. typhimurium could activate complement by either the classical or the alternative pathway. The presence of antibody did not alter alternative pathway activity but enhanced the classical pathway activity, especially for those strains possessing intact core structure and in the presence of 10% serum. This effect of antibody on classical pathway activation decreased as the lipopolysaccharide chain length decreased. The finding that the presence of antibody reduced the classical pathway activity in the opsonization of SL 1032 (Rd1) strain in 10% serum was unexpected. This suggests that if complement activity in the absence of antibody is already marked, the presence of antibody cannot increase it further. Inhibition was also found in the interaction between classical and alternative pathways. For SL 1032 (Rd1) strain, in the absence of antibody, either classical or alternative pathway activity alone could be maximally activated in 10% serum and when present together were in competition with each other. The interaction, either enhancement or inhibition, was not only dependent on the individual strain but also on the concentration of serum. In general, enhancement occurred in the presence of 1% serum while inhibition was observed in the presence of 10% serum. Such antagonistic interaction has not previously been reported. PMID- 3102177 TI - Effect of EGTA on phagocytosis of Salmonella typhimurium by human neutrophils. AB - The ingestion of mutant strains of Salmonella typhimurium by human neutrophils was greatly reduced by the presence of ethylene glycol tetra-acetic acid (EGTA) in the reaction mixture. Ingestion of preopsonized bacteria by neutrophils was little affected by Ca++ in the reaction mixture but largely reduced by the presence of EGTA. In addition to chelation of Ca++, EGTA has an adverse effect on neutrophils. In studies of phagocytosis, to avoid this effect, EGTA should not be present in the reaction mixture when it is used to prevent the complement classical pathway activation. PMID- 3102178 TI - Alteration of nitrogenase activity of Anabaena CH1 and CH2 during light-dark transition. AB - Nitrogenase activity decreased as cultures transferred from light to the dark. In anabaena CH1 nitrogenase activity ceased to near zero in two hours; but it took longer in Anabaena CH2. When darkened culture was placed again in the light, nitrogenase activity recovered in two hours. Hydrogen gas could protect this dark declination of nitrogenase activity. It is suggested that dark declination of nitrogenase activity is due to irreversible inhibition by oxygen which can not be omitted through oxidative respiration and/or oxyhydrogen reaction in the dark. PMID- 3102179 TI - [An improved, more flexible nasointestinal feeding tube]. PMID- 3102180 TI - [Intravesical application of thio-tepa for preventing postoperative recurrence of bladder carcinoma]. PMID- 3102181 TI - Pharmacokinetics of temocillin after intravenous and intramuscular administration. AB - Pharmacokinetics of temocillin (BRL 17421) was studied in a crossover study in 10 male healthy volunteers after administration 1 g of temocillin intravenously or intramuscularly. The mean serum levels of temocillin at the 5th min after i.v. administration were 131.57 mg/ml, at 1 h 71.27 mg/l and at 12.12 mg/l. The values of the pharmacokinetic parameters were as follows: AUC 509.2 mg X h X l-1, t1/2 4.2 h-1, Vd ss 11.57 l, Vd area 12.28 l, CL 2049 ml X h-1. The urinary excretion by 12 h was 70.58% of the administered dose of temocillin. The mean serum levels of temocillin after i. m. administration were at 2 h 46.65 mg/l and at 12 h 15.89 mg/l, the corresponding pharmacokinetic parameters were: AUC 501.38 mg X h X l-1, t1/2 4.3 h-1, Vd 12.69 l. The urinary excretion by 12 h was 57% of the administered dose of temocillin. It follows from the study that pharmacokinetic parameters of temocillin after both ways of temocillin administration are very closed and that the dose 1 g of temocillin is sufficient to create effective serum levels for the majority of sensitive gramnegative organismus. PMID- 3102182 TI - Comparison of serum and coagulum antibiotic levels with respect to protected blood coagulum. AB - Serum and coagulum antibiotic levels have a parallel course. Coagulum antibiotic concentrations are more than ten times lower than serum concentrations. Therefore the optimal dosage of perioperative infusion should be high enough to establish steady state by means of sufficiently high serum levels. Antibiotics capable of attaining high serum levels and having a long half-life are best suited for the formation of effective antibiotic concentrations in blood coagulum. This is particularly true for cephalosporins and penicillins. Aminoglycoside antibiotics are not recommended for the formation of protected coagulum. "Ceftriaxon in the treatment of Severe bacterial infections". PMID- 3102183 TI - Ceftriaxon in treatment of bacterial meningitis. AB - The authors tested cephalosporin antibiotic of the 3rd generation--Ceftriaxon--in treatment of bacterial meningitis. After studying the infiltration of the antibiotic into the cerebrospinal fluid in 13 patients with parotitic meningoencephalitis, the authors treated 15 patients with bacterial meningitis. Ceftriaxon has been applied in 100 mg/kg in two doses i.v. The research antibiotic levels in cerebrospinal fluid varied from 10 to 30% of sera levels and were much higher than MIC for pathogens isolated from liquor. The treatment effects were very good the dropping of temperature followed on the 3-4 day, the 5 6, day under 100/3. The side effects showed a short time increasing of transaminases and diarrhoea. After completing the treatment normalisation occurred quickly. Other side effects have not occurred. The authors can state, Ceftriaxon in treatment of bacterial meningitis is a highly effective antibiotic. PMID- 3102184 TI - Long-term experience with combined action of antibacterials. AB - The authors have obtained good results in control of respiratory infections in children (aged 3-9 years) (especially those with dg. pneumonia) when applying a combination of amoxicillin with clavulanic acid. Correct indication has enabled them to shorten the period of treatment by means of this combination. The interaction of ticarcillin with some aminoglycoside preparation has been verified in vitro. Synergic action has been found to be high. PMID- 3102185 TI - Control of Pseudomonas sepsis in mice with azlocillin combined with gentamicin. AB - The antibacterial activity of azlocillin VUFB and gentamicin was tested in vivo. To mice with Pseudomonas sepsis the test substances were injected either alone or combined, and the mortality was assessed. The test substances were freeze dried injectable azlocillin and gentamicin (Pharmachim). Azlocillin was injected into mice either intravenously or intramuscularly in graduated doses of 50-500 mg/kg once daily. The therapeutic effect was assessed on the basis of survival of the treated mice. Our expectation of a potentiated effect of the azlocillin gentamicin combination was confirmed. After intramuscular administration of azlocillin plus gentamicin 90% of the mice survived, in comparison with 40% only after either azlocillin or gentamicin alone. PMID- 3102186 TI - In vivo effect of aminoglycoside on Pseudomonas aeruginosa in experiment. AB - In artificial pseudomonas infections undertaken on white mice the effectiveness of the aminoglycosides (gentamicin, tobramycin, netilmicin, amikacin) was compared. The most effective drugs on highly susceptible Ps. aeruginosa were amikacin and netilmicin. Moreover amikacin is probably capable of inhibiting pseudomonas toxin production. Therefore this preparation should be left in reserve for the treatment of serious pseudomonas processes. PMID- 3102187 TI - Humoral factors of resistance in the cohort of workers exposed to vinylchloride in the span of six years, concerning the influence of smoking. AB - A cohort of 66 workers professionally exposed to vinylchloride (VC) in a plant producing polyvinylchloride was examined in years 1979 and 1985 by same methods. Significant changes of the levels of immunoglobulins (Ig), lysozyme and transferrin were not observed during the six years in the subgroup of smokers. Nevertheless a highly significant rise of alpha 2 macroglobulin (A2M) and ceruloplasmin (CPL) levels in this subgroup was stated. The levels of IgA and IgM significantly rose in the subgroup of ex-smokers, as well as highly significant increase of A2M was noted in this subgroup. The levels of IgG and A2M rose with highly significance in the subgroup of non-smokers; the CPL increase was only of weak significance. Many significant differences in means were assessed between subgroups of exposed workers and age matched control persons. No significant correlation between the levels of the tests and the time of exposure to VC was observed by regression analysis. In the discussion an opinion about possible premature aging of persons exposed to VC was brought forward. PMID- 3102188 TI - Indications of primary osteosynthesis in patients with fractures of long bones of extremities with special regard to multiple and associated fractures of femur diaphysis. AB - Fractures of the long shaft-shaped bones were evaluated upto the sixties as an isolated therapeutic problem. During the past fifteen years, however, views as regards treatment of fractures of long bones began to change along with the increasing number of multiple fractures and polytraumas. It was revealed that fractures of the long bones and pelvic fractures have a bearing on the development of the syndrome of fat embolism, the syndrome of acute respiratory distress in adults, on the development of shock damage of the lungs, heart, kidneys, liver, pancreas etc. Evidence was accumulating that unstable fractures of the long shaft-shaped bones contribute towards the development of these complications. During the past ten years stable osteosynthesis of fractures of the long bones, in particular of the lower extremities, has gained priority among operations which have a positive effect on the stabilization of the organism in the early postinjury stage of polytrauma. Modern traumatology solves the dilemma which developed in practice from the need of early osteosynthesis on the one hand and reflections on possible deterioration of the general condition of the organism of the severely injured as a result of urgent or early osteosynthesis, on the other hand. Modern traumatology seeks a basis for objective assessment of conditions and parameters for possible primary or early delayed osteosynthesis in multiple injuries with the aim to shift the indication for stable osteosynthesis of fractures of the femur in multiple injuries to the onset of the stabilization phase. PMID- 3102189 TI - Response of porcine lower esophageal sphincter to increasing intraabdominal pressure. AB - The response of lower esophageal sphincter pressure to increasing intraabdominal pressure was investigated in six anesthetized pigs while measuring the intraabdominal pressure directly with a perfused catheter and recording continuously from the lower esophageal sphincter using a manometric catheter incorporating a constantly perfused sleeve. Studies were conducted both before and after the administration of intravenous atropine. Resting lower esophageal sphincter pressure was 8 mm Hg (3-19 mm Hg). In response to inflation of the peritoneal cavity with carbon dioxide gas, lower esophageal sphincter pressure rose significantly more than intraabdominal pressure whether the stomach was empty or full. In three of the six pigs, phasic lower esophageal sphincter pressure variations occurred as intraabdominal pressure increased. These variations were unrelated to respiration. Resting lower esophageal sphincter pressure was little affected by 75 micrograms/kg intravenous atropine which also had no effect on the lower esophageal sphincter response to increasing intraabdominal pressure. We conclude that, in the pig, the lower esophageal sphincter pressure increases more than the intraabdominal pressure in response to challenge and that excitatory cholinergic fibers do not mediate this response. PMID- 3102190 TI - Postheparin plasma diamine oxidase in subjects with small bowel mucosal atrophy. AB - Diamine oxidase (DAO) is an enzyme whose low plasma values are enhanced by an intravenous injection of heparin, which releases the enzyme from the enterocytes of the villous tips. In 20 normal controls and 15 untreated subjects affected with an overt malabsorption syndrome and subtotal atrophy shown by Crosby jejunal mucosa biopsy (12 suspected celiac disease and three small bowel lymphoma), plasma diamine oxidase was assayed, over 2 hr following an intravenous bolus of 15,000 IU heparin. Plasma postheparin DAO concentrations and the corresponding values of the area under curve, expressed as units/ml X min (mean +/- SD), were significantly lower in the patients (celiac sprue: 138 +/- 62; lymphoma: 83 +/- 42) compared to normals (481 +/- 104). DAO area values were well correlated (r = 0.81; P less than 0.001) with 24-hr fecal fat excretion but not with xylosuria. Our data suggest that postheparin plasma DAO assay may be useful to detect and quantitate small bowel mucosal atrophy in patients with malabsorption syndromes. PMID- 3102191 TI - The effect of age, gender, and sexual maturation on the caffeine breath test. AB - This study demonstrated the feasibility of utilizing the (3-13C-methyl) caffeine breath test (CBT) in children and adolescents, and examined the effect of gender, age, and puberty on the CBT. The CBT, expressed as the 2-hour accumulative exhalation of labeled CO2 (2-hour CO2), was compared to the CBT results in the adult. The 2-hour CO2 values were higher in the children than the adult, and the decrease in the CO2 values occurred in males during late puberty and in females during early puberty. PMID- 3102192 TI - Microencapsulation of pancreatic islets. A technique and its application to culture and transplantation. AB - Hamster pancreatic islets were encapsulated by a biocompatible membrane composed of the molecular sequence of alginate-polylysine-alginate. The encapsulated islets released insulin into the culture medium in response to secretagogues in short-term incubation. In long-term culture, the encapsulated islets maintained their insulin-releasing capacity for 28 days at a level similar to that of the unencapsulated islets. No overgrowth of fibroblastic cells was observed inside the capsule even after 70 days of culture. Further, the encapsulated hamster islets were xenotransplanted to streptozotocin-induced diabetic rats intraperitoneally. Some of the encapsulated islets, which were recovered from a recipient 27 days after transplantation, were found to be viable, although prolonged normalization of fasting plasma glucose levels of the recipients could not been achieved. On the contrary, the unencapsulated islets were replaced by massive connective tissue elements and insulin-positive B cells were hardly detected within the grafts 22 days after transplantation. The results of this study seem to confirm the potential of the application of the encapsulating technique to primary culture of parenchymal cells and to transplantation of pancreatic islets. PMID- 3102193 TI - [Population-genetic study of Drosophila melanogaster from the Seychelles: frequency of alleles of allozyme loci and morpho-physiological traits]. PMID- 3102194 TI - Study of in vitro selected resistance of Pseudomonas aeruginosa to cefoperazone, ceftazidime, azthreonam and imipenem. AB - Ten strains of Pseudomonas aeruginosa were plated on agar containing cefoperazone, ceftazidime, azthreonam or imipenem alone and in combination with ampicillin or cefoxitin as inducers, and/or amikacin (MIC/4), according to Szybalsky. Regrowing colonies were randomly selected for MIC and MBC determinations. The numbers of regrowing colonies were occasionally increased by a beta-lactamase inducer, although amikacin significantly reduced it. Some 243 colonies were further studied. The most frequent phenotypes of resistance (195 mutants) were: resistance to cefoperazone, ceftazidime, azthreonam (99 regrowing colonies); resistance to cefoperazone, azthreonam (36); resistance to cefoperazone (17); resistance to cefoperazone, ceftazidime, azthreonam, imipenem (17). A total of 28/31 R mutants retained their phenotype after 15 subcultures in antibiotic-free medium. The mutants R cefoperazone, ceftazidime, azthreonam were studied by quantitative beta-lactamase evaluation in agar with substrate and non substrate antibiotics, substrate profile study spectrophotometrically, crypticity study by comparing beta-lactamase activity of intact and sonicated cells spectrophotometrically, isoelectric focusing of sonicate extracts and dialysis experiments for trapping evaluation. These mutants were characterized by a 240 fold increase in beta-lactamase production (Pi = 8.7) and unchanged permeability. beta-lactamase trapping was demonstrated but could not explain alone the phenotype of resistance. These studies suggest that mutants constitutive for beta lactamase production were easily selected in vitro. Amikacin was able significantly to prevent their emergence. PMID- 3102195 TI - [Measuring the regional blood flow with 51Cr labelled formalinized toad red blood cells]. PMID- 3102196 TI - Abuse potential evaluation of inhalants. AB - Although inhalant abuse remains an important worldwide drug abuse problem, little is known about the relative abuse liability of specific inhalant compounds. This paper reviews approaches which might be used to investigate the abuse potential of inhalants in the laboratory, focusing primarily on animal studies. The principal approaches considered are inhalant self-administration and discrimination studies. A need is identified for further investigations of the abuse potential of inhalants to provide data which should be useful in shaping a more effective public health response to inhalant abuse. PMID- 3102197 TI - Topical mupirocin in the treatment of bacterial skin infections. AB - Mupirocin is an investigational topical antibiotic used for treatment and prophylaxis of bacterial skin infections. Mupirocin differs from other antibiotics in its synthesis, structure, and mechanism of action. In vitro, mupirocin possesses antimicrobial activity against staphylococci, streptococci, Hemophilus influenzae, and Neisseria gonorrhoeae. Few studies comparing mupirocin to other topical antibiotics are available. Initial studies comparing mupirocin to inactive vehicle in the treatment of impetigo indicate an overall 92 percent pathogen eradication rate with active drug and 58 percent eradication rate with vehicle. Overall response to treatment of secondary skin infections was favorable in 91 percent of patients treated with mupirocin and 77 percent of those treated with vehicle. Although incidence is not greater than placebo, adverse effects have included pruritus, burning, dry skin, and erythema. Additional trials and clinical use should further help determine the role of mupirocin in the treatment of minor, primary, and secondary skin infections. PMID- 3102198 TI - Cromolyn sodium: a review of mechanisms and clinical use in asthma. AB - The cellular and clinical pharmacology of cromolyn sodium are reviewed. Cromolyn sodium inhibits the release of mediators of inflammation, induced by specific antigens as well as nonspecific mechanisms, such as exercise, from mast cells. Cromolyn may also inhibit the activity of other cell types that produce inflammation. It is the only antiasthmatic that blocks both early and late asthmatic responses induced by allergen inhalation and exercise. Consequently, cromolyn therapy can block the increase in bronchial hyperreactivity induced by chronic allergen exposure. Cromolyn is effective for controlling the symptoms of mild to moderate chronic asthma in 60 to 70 percent of patients. In comparative studies, cromolyn has been as effective as theophylline for controlling symptoms of chronic asthma with fewer side effects, and may be particularly suited for asthmatic patients with learning or behavioral problems. The combination of theophylline and cromolyn is often more effective than either agent alone. Because of the convenience of administration, cromolyn is preferred over theophylline for exercise-induced asthma. Cromolyn may allow the corticosteroid dosage to be reduced in severe steroid-dependent asthmatics, but it is primarily indicated for the prophylaxis of mild to moderate disease. Adverse reactions to cromolyn are uncommon to rare. Cromolyn is now available in a Spinhaler, a metered-dose aerosol, and a nebulizer solution. If taken properly all preparations appear to be equally effective. Attention to proper inhalation technique and appropriate education of the patient is essential to ensure a good outcome with cromolyn. PMID- 3102199 TI - Cromolyn sodium for childhood asthma: a drug whose time has come. PMID- 3102200 TI - Drug Information Center network: need, effectiveness, and cost justification. AB - During the past 15 years, the pharmacy profession has experienced much change. Certain pharmacy roles are being challenged and others are coming into existence. Today, health-care practitioners and health-care providers are seeking services not sought before from pharmacists in the area of rational therapeutics. This need for information extends to all pharmacy practice settings: institutional, independent pharmacies, chain stores, governmental agencies, and the pharmaceutical industry. In order to meet this demand for drug and toxicology information, however, the pharmacist must use resources outside the immediate area of his practice. The Drug Information Center (DIC) can be used as such a resource by pharmacists in their daily practice to provide the best possible care with regard to the rational use of drugs for their patients/clients. Specifically, our data indicate that in Tennessee, there is a need for providing drug and toxicology information; pharmacists perceive their role to be providers of drug information as well as drugs; the DIC plays an integral and necessary role as a back-up information resource and in teaching, service, research, and continuing education programs; and the programs provided by the DIC are cost effective and cost justifiable. PMID- 3102201 TI - [Listeriosis today]. PMID- 3102202 TI - Diazepam metabolism in the guinea pig materno-fetal model: effects of cigarette smoke. AB - The transplacental acquisition, disposition and biotransformation of diazepam (DZ) was investigated in the pregnant guinea pig at 65-67 days of gestation following the administration of single oral doses of 10 mg/kg body weight, the dams and fetuses being euthanized 60 min post-treatment. Tissues (blood plasma, liver, brain, perirenal fat and placenta) were removed for drug residue analysis. Nordiazepam (NDZ) was the only metabolite produced by guinea pigs in vivo. Residues of DZ and NDZ were found in fetal tissues, indicating that the placenta was not an effective barrier. The influence of cigarette smoke on in vitro DZ biotransformation was studied by exposing pregnant guinea pigs (55-57 days of gestation) to ambient air (control) or cigarette smoke thrice daily for 10 consecutive days. At term (day 67), the fetuses were delivered by caesarean section for the preparation of hepatic and placental microsomes to measure the metabolism of DZ. DZ was converted at a slow rate into NDZ by fetal hepatic and placental microsomes in vitro. Exposure to cigarette smoke had no effect on DZ metabolism by the dam liver or by the placenta but a 2-4-fold increase in NDZ formation was observed in fetal hepatic microsomes. PMID- 3102203 TI - Differences in the in vivo and in vitro effects of the carbamate insecticide, carbaryl on rat hepatic monooxygenases. AB - The effects of one of the most widely used insecticides, carbaryl, on the hepatic cytochrome P-450-dependent monooxygenases were determined. Addition of carbaryl to liver microsomes from untreated or phenobarbital (PB)-pretreated rats resulted in a weak Type I binding spectrum. A much stronger spectral Type I interaction was observed when microsomes from 3-methylcholanthrene(3-MC)-treated rats were used. In vitro, carbaryl caused marked inhibition of ethylmorphine and benzphetamine N-demethylases, benzo(a)pyrene hydroxylase, 7-ethoxycoumarin and 7 ethoxyresorufin O-deethylase in liver microsomes. Kinetic studies demonstrated that carbaryl was a competitive inhibitor of ethylmorphine N-demethylase activity. Daily administration of carbaryl for 4 days by gavage or intraperitoneally resulted in no significant alterations in hepatic cytochrome P 450 levels, ethylmorphine N-demethylase or benzo(a)-pyrene hydroxylase activities. The lack of effect of carbaryl in vivo may be due to the rapid metabolism of the insecticide, such that the insecticide may not be present in the liver endoplasmic reticulum to cause the inhibitory effects observed in vitro. PMID- 3102204 TI - Effect of aflatoxin B1 on some liver microsomal enzymes in mice fed cyanide supplemented diets. AB - Aniline hydroxylase, glucose-6-phosphatase, NADPH- and NADH-cytochrome C reductase activities were measured in liver microsomes prepared from four groups of female mice. Mice were fed either control diets alone or KCN (0.357, microgram/kg body wt/day) supplemented diets or control diets plus AFB1 (0.35 microgram/kg body wt/day) administration (ip) on the 8, 9 and 10th day or the KCN supplemented diet plus AFB, administration (ip) on the 8, 9 and 10th day. KCN and AFB1 consistently elevated the activities of the enzymes. Simultaneous administration of both toxins potentiated their effects on the enzymes with the exception of glucose-6-phosphatase. Increases in microsomal protein/liver wt ratios, liver wt/body wt ratios and these enzyme activities were probably indicative of microsomal enzyme induction. PMID- 3102206 TI - What's your PPI? PMID- 3102207 TI - Extramedullary plasmacytoma of the parotid gland. PMID- 3102208 TI - Influence of the dosing interval on the response of urinary schistosomiasis to therapy with niridazole. PMID- 3102205 TI - Misoprostol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of peptic ulcer disease. AB - Misoprostol is an analogue of prostaglandin E1 and is the first synthetic prostaglandin analogue to be made available for the treatment of peptic ulcer disease. It inhibits gastric acid secretion in man, and there is also some evidence that it limits the extent of gastrointestinal damage induced by ulcerogenic agents in animals and healthy volunteers at doses lower than those required to inhibit acid secretion. This 'cytoprotective' activity has been explained by several mechanisms, but its contribution to the clinical efficacy of misoprostol in healing established ulcers is doubtful since the drug does not appear to be effective in healing peptic ulcers at non-antisecretory dosages. In clinical trials, ulcer healing has been reported in 60 to 85% of patients with duodenal ulcers and 32 to 54% with gastric ulcers receiving misoprostol 200 micrograms 4 times daily for 4 weeks--the recommended dosage. In comparative studies, the percentage of patients with healed ulcers after misoprostol (800 micrograms daily) was not significantly different from that with cimetidine (1200 mg daily), although there was greater pain relief with cimetidine. No study has yet been published concerning the use of misoprostol as maintenance therapy for the prevention of ulcer recurrence, and no long term tolerability data are available. However, in acute ulcer healing studies (2 to 12 weeks in duration) misoprostol has been well tolerated. Diarrhoea was the most commonly reported symptom, and this was only rarely of sufficient severity to interfere with treatment. No evidence of histopathological changes in the gastric mucosa induced by misoprostol have been reported in man. Evidence of uterine stimulant effects in women receiving misoprostol during the first trimester of pregnancy has resulted in the drug being contraindicated during pregnancy. Thus, misoprostol is a new type of antiulcer drug, providing an alternative approach to the therapy of peptic ulcer disease. It has been shown to be effective and well tolerated in the healing of both gastric and duodenal ulcers. Future studies need to identify the specific types of patients likely to obtain most benefit from treatment, in order to define more clearly the place of misoprostol in the treatment of these indications, as well as addressing the possibility of ulcer prevention with lower doses of misoprostol. PMID- 3102209 TI - The evaluation of maternal anti-D concentrations during pregnancy. AB - Anti-D quantitation by the AutoAnalyzer technique has been shown to be a helpful aid in assessing the severity of D alloimmunization during pregnancy. In this study, the technique has been used both to detect antibody boosting after amniocentesis and to differentiate active D immunization from the presence of passive antibodies. The AutoAnalyzer technique and the more generally used indirect antiglobulin test titration method showed good agreement at titre levels of 32 or lower. A titre of 32 was found to be a good discriminative level to separate the mildly affected from the more severely affected newborns suffering from Rh haemolytic disease. At higher titre levels, however, the AutoAnalyzer technique was the method of choice for correct clinical assessment of the severity of D alloimmunization. PMID- 3102210 TI - A management programme for Rh alloimmunization during pregnancy. AB - A management programme for the control and treatment of Rh0 (D) immunized during pregnancy is presented. A total of 34,650 births were registered during a 4.5 year period and included 63 D positive newborns to D-immunized mothers. The outcome of all infants has been evaluated according to the severity of the haemolytic disease. Exchange transfusion was unnecessary in 43 mild cases (68.3%). Fourteen infants (22.2%) required exchange transfusion, and in 6 severe cases (9.5%) maternal plasma exchange and exchange transfusion was performed. No detrimental effects or deaths occurred among the infants suffering from Rh haemolytic disease. We recommend that the frequency and volume of plasma exchange therapy should be individually adjusted to suit each patient and the effect monitored regularly through maternal anti-D levels using a sensitive quantitative technique. PMID- 3102212 TI - Evaluation of the test method "activated sludge, respiration inhibition test" proposed by the OECD. AB - The test method of "activated sludge, respiration inhibition test" proposed by the OECD was critically carried out and compared with other test methods. Investigation of test conditions showed that the moderate deviation from the test conditions defined by the OECD Test Guidelines did not have much effect on the result, and some modifications were proposed to improve the method. This method had a poor detection limit compared with the LC50 test with Oryzias latipes and EC50 of the growth inhibition test with Tetrahymena pyriformis. The susceptivity of the method was particularly poor for the chemicals which were highly toxic in the other two tests. PMID- 3102211 TI - Randomized controlled trial of very early continuous distending pressure in the management of preterm infants. AB - Application of continuous distending pressure at birth (very early CDP) should stabilize the immature airways and reduce the severity of respiratory distress syndrome (RDS) in preterm infants. Eighty-two preterm infants of less than 32 weeks gestation were randomly assigned at birth to early treatment group (TG), in which CDP of 6 cm water pressure was applied at birth by the nasopharyngeal route (NP-CDP), or to control group (CG), in which CDP was applied when indicated for established criteria (pO2 less than 50 mmHg in FiO2 greater than 0.5). Characteristics of the infants in the two groups were comparable. No statistically significant difference between the two groups was found in the incidence of RDS. The course of RDS, and oxygen and ventilatory requirements also did not appear to be changed. In blood gas parameters of most of the time frames, no significant difference was found between the two groups when the results were analyzed according to the assigned group. When the results were analyzed separately for the infants who developed RDS, infants in TG appear to have fared worse from the therapy in terms of oxygenation, as indicated by significantly higher FiO2 (P less than 0.01) and lower a/A (P less than 0.01) values on the third day of the course of RDS, as compared to infants in CG. The incidence of complications was comparable in the two groups. Four infants from TG (9.3%) and one from CG (2.6%) died (P = NS). We conclude that VECDP by nasopharyngeal route does not reduce the incidence of RDS and does not appear to improve the outcome and may worsen the severity of RDS when compared to application of CDP for established criteria. PMID- 3102213 TI - [Enzymatic changes in burns and their treatment with amino acid solutions]. PMID- 3102215 TI - [Cytotoxic factors of neutrophils in rats with 7,12-dimethylbenz[a]anthracene induced sarcoma]. AB - A study of intraleukocyte cytotoxic system and phagocytic function of granulocytes was carried out in rats with 7,12-dimethylbenz(a)anthracene-induced sarcoma. There were no distinctive alterations of microbicidal factors of polymorphonuclear neutrophils (PMN) at the initial stage of the tumour growth. The inhibition of some antibiotic neutrophil factors at later stages of the tumour growth in rats was compensated by preferential activity of others. The essential impairments of both the oxygen-dependent and oxygen-independent mechanism of cytotoxicity of PMN at the terminal stage of sarcoma growth were detected. At the same time the phagocytic activity of neutrophils was depressed. PMID- 3102214 TI - [Non-specific antitumoral activity of staphylococcal enterotoxins]. AB - St. aureus enterotoxins A and B possess an antitumour effect. After intraperitoneal inoculation they decrease the size and in some cases prevent the development of the human hypernephroma in the cheek pouch of golden hamsters. The effect of enterotoxins may possibly consist in inducing the production of endogenous immune interferon which activates the host immune system and enhances the rejection of heterologous tumour cells. PMID- 3102216 TI - Use of computers in emergency department practice. AB - This article discusses current applications of computers in the Emergency Department. Different approaches for computerization are compared, and difficulties and problems of computerization are discussed. PMID- 3102218 TI - Effect of sodium valproate on psychomotor performance in children as a function of dose, fluctuations in concentration, and diagnosis. AB - Forty-six children receiving sodium valproate monotherapy, and with well controlled seizures, were tested three times, at weekly intervals in the morning, on an extensive battery of psychomotor tests. The first session was a practice session to minimize subsequent practice effects. On one of the remaining 2 test days, morning medication was delayed until after testing (low concentration condition), whereas sodium valproate was given before testing on the alternate session (high concentration day). The data were analyzed for the effects of diagnosis (partial vs. generalized epilepsy), dose (above or below 20 mg/kg/day), and time of medication (low and high drug concentration days). Four variables discriminated between the diagnostic groups, all favoring children with generalized epilepsy. Another four measures were significantly associated with dose, with those on lower doses performing at a superior level. Time of medication had virtually no effect on performance, however. The findings were related to previous diagnostic and dosage research. Although a deterioration in performance at higher doses appears to be consistent with other dosage research, the absence of an effect due to time of medication suggests that performance does not fluctuate between drug administrations. PMID- 3102217 TI - Deposition of large particles in human lung. AB - Twenty-four nonsmoking males, all without history of pulmonary disease, were randomly divided into four groups of six subjects each. The subjects in each group inhaled monodisperse Teflon particles labelled with 111In (half-life 2.83 days); 8.2, 11.5, 13.7 and 16.4 micron aerodynamic diameter, respectively. Radioactivity in head and throat, lung and stomach was determined after 0, 3 and 24 hrs using a profile scanner. For some subjects radioactivity was also determined using a whole-body scanner at 3.5 and 24 hrs. After the 24-hr determination the subjects inhaled labelled Teflon particles again, this time with a filter in front of the mouth. Average values for total deposition in the body, obtained using a profile scanner, whole-body scanner and filter measurements, agreed fairly well. Lung retention values obtained by whole-body and profile scanning also agreed well. The average deposition in the lung, expressed as a percentage of total deposition, was 49, 31, 21 and 13% for the four particle sizes (8.2-16.4 micron). Alveolar deposition, determined as retention at 24 hrs and expressed in percent of total deposition, was 15, 4, 4 and 1%. For the smallest particle sizes the deposition values agreed with earlier investigations. However, for the larger particles the two deposition values were higher than expected when compared to earlier studies. PMID- 3102219 TI - Hepatotoxicity in rat following administration of valproic acid. AB - Chronic injections of valproic acid (VPA), VPA with phenobarbital (PB), and PB were studied for their effects on liver mitochondrial morphology and carnitine metabolism in rats. Mitochondrial enlargement was induced by the administration of VPA (500 mg/kg/day) for a period of 7 consecutive days. The administration of VPA (500 mg/kg/day)-plus-PB (20 mg/kg/day) for 7 days, however, did not induce megamitochondrial formation, but in these livers an unusual increase was observed in the number of liver mitochondria, microvesicular steatoses, and myeloid bodies. VPA-treated rats had significantly lower levels of serum-free and total carnitine and higher levels of acylcarnitine and acyl to free ratio than those of the controls. The free carnitine concentrations in serum and liver of the rats treated with VPA-plus-PB were much lower as compared with those treated with either VPA or PB. These morphological and biochemical results, especially of carnitine metabolism, suggest that inhibition of beta-oxidation in liver mitochondria occurred in rats treated with VPA and PB and that, in particular, polytherapy with VPA-plus-PB could be clinically hazardous in causing hepatic injury. PMID- 3102220 TI - Comparison of the effects of valproate, ethosuximide, phenytoin, and pentobarbital on cerebral energy metabolism in the rat. AB - The acute effects of valproate (200 and 400 mg/kg), ethosuximide (200 and 400 mg/kg), phenytoin (25 and 50 mg/kg), and pentobarbital (30 and 60 mg/kg) on cerebral energy metabolism of rats were studied by measuring the cerebral content of energy metabolites and by evaluating the rate of metabolite utilization following decapitation. The treatments did not affect the levels of phosphocreatine (PCr), ATP, ADP, and AMP, but did enhance the glycogen or glucose stores. Pentobarbital induced a decrease in lactate, whereas valproate led to a decrease in pyruvate and an increase in lactate. Calculation of the metabolite fluxes after decapitation showed that all treatments delayed the rate of ATP utilization. The response was dose-dependent except with valproate. In addition, pentobarbital led to reductions in glucose utilization and lactate production, but the other drugs had no significant effect on glycolysis rate. The sparing effect on ATP utilization may be related to a membrane-stabilizing effect and may provide brain protection in case of excessive neuronal activation. PMID- 3102221 TI - Effect of seizures on brain phenobarbital concentration in newborn piglets. AB - Phenobarbital (PB) brain and blood concentrations were measured together with brain and blood pH in newborn piglets before and at the end of seizure activity induced by pentylenetetrazol or bicuculline. Seizures induced a significant elevation of arterial blood pressure and profound changes in the blood gases and in the acid-base balance, with a marked reduction in brain tissue pH. Despite an intense brain acidosis, however, and a significant rise in blood/brain [H+] gradient, phenobarbital brain concentrations were not reduced during seizures but, on the contrary, were increased in 7 of 11 piglets. These data suggest that contrary to the pH partition hypothesis, brain uptake of PB is concomitantly increased during seizures and brain acidosis. PMID- 3102222 TI - The lens and cataract: clastogenic responses in epithelial cells of the organ cultured rat lens. AB - The epithelial cells of the vertebrate lens have an unique character and a probable involvement in cataract formation, which could be initiated by exogenous stimuli. Individual rat lenses were organ-cultured, and the effects of mitomycin C and gamma rays on sister chromatid exchanges (SCE), chromosomal aberrations, and cellular kinetics assessed in cells from the epithelial monolayer. SCE showed about a 5.5-fold increase over the mitomycin C dose range (0, 17, 83, 170 nM), while chromosomal aberrations increased 38-fold. In cells from untreated lenses, SCE were 1,600 times more frequent than aberrations and at a level consistent with in vivo assessments in other cell types. Gamma rays (up to 4 Gy) had a greater inhibiting effect on cellular progression, while 17 nM mitomycin C and 1 Gy induced similar clastogenic responses. This first demonstration of such changes in lens epithelial cells expands on the cell types available for monitoring potential mutagen-carcinogens. Additionally chromosomal changes resulting from lens cellular challenge could be the basis of later cytopathological changes in the lens, of which cataract is the primary concern to humans. Potential cataractogens warrant monitoring, and the study outlined may aid in this endeavor, as well as contributing to an understanding of cataract etiology. PMID- 3102223 TI - Responses of the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay to coded chemicals. I: Results for nine compounds. AB - Nine substances were tested for their mutagenic potential in the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay, by means of procedures based upon those described by Clive and Spector (Mutat Res 44:269-278, 1975) and Clive et al (Mutat Res 59:61-108, 1979). 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 coded chemicals were tested at least twice. Significant responses were obtained with calcium chromate, 3 (chloromethyl)pyridine, 1,2-epoxybutane, monochloroacetic acid, dicyclohexylthiourea, 2,4-diaminophenol hydrochloride, and pentachloroanisole. Apart from pentachloroanisole, rat liver S9 mix was not a requirement for the clearly mutagenic activity of any of these compounds. Compounds not identified as mutagens were 3-amino-1,2,4-triazole and sucrose. PMID- 3102224 TI - The progress and prospects of health psychology: tasks of a maturing discipline. AB - Substantial research advances and professional articulation have brought the field of health psychology to a certain level of maturity. From a research standpoint, we are ready to meet the challenge of the biopsychosocial model. Professionally, the field must continue to demonstrate treatment effectiveness and cost-effectiveness, integrate basic science with applications, consider how best to market health psychology research, develop criteria for intervention, and agree on training standards for researchers and professionals in the field. Current trends toward complex, multidisciplinary programs of research, and lengthy training programs may, however, conspire to drive away talented young investigators. The field can anticipate and potentially solve some of these problems by drawing on the cooperative scientific vision that has characterized our field to date. PMID- 3102225 TI - Wheelchair ergonomics and physiological testing of prototypes. PMID- 3102226 TI - Use of a recombinant retrovirus to study post-implantation cell lineage in mouse embryos. AB - We show that a gene introduced into cells of mouse embryos by a retrovirus can serve as a heritable marker for the study of cell lineage in vivo. We constructed a defective recombinant retrovirus in which the Escherichia coli beta galactosidase (lacZ) gene is inserted in the genome of a Muloney murine leukemia virus (M-MuLV). Expression of lacZ was detected with a histochemical stain that can be applied to cultured cells and embryonic tissue. Infection of cultured cells showed that lacZ has no detectable deleterious effects on cell viability or growth, that the enzyme is stably expressed in the progeny of infected cells for many generations in the absence of selective pressure, and that the virus can induce lacZ in a variety of cell types. Following injection of the virus into mid gestation mouse embryos, clones of lacZ-positive cells were detected in skin, skull, meninges, brain, visceral yolk sac, and amnion. We identified the cell types comprising a series of lacZ-positive clones in the visceral yolk sac and skin to learn the lineage relationships of the labelled cells. In each tissue, we obtained evidence that several cell types have a pluripotential ancestor and that cell fate is progressively restricted as development proceeds. PMID- 3102227 TI - Nuclear factors binding specific sequences within the immunoglobulin enhancer interact differentially with other enhancer elements. AB - The mouse immunoglobulin heavy chain (IgH) enhancer represents a cis essential control element that confers lymphoid-specific expression. Based on in vivo and in vitro competition experiments, as well as on in vivo dimethylsulfate (DMS) protection experiments, it has been inferred that cellular factors interact in trans with IgH enhancer sequences. In addition, transcription is stimulated in vitro by up to one order of magnitude in the presence of IgH enhancer sequences on an appropriate template. Thus, at least some of these factors have to be present in nuclear extracts. To examine the factors interacting with this lymphoid-specific enhancer in more detail we compared the binding pattern of nuclear factors present in B-cell, T-cell and HeLa cell extracts. We demonstrate here, using the DNase I and DMS protection methods, the specific interaction of three different nuclear factors with the central PstI--EcoRI fragment of the IgH enhancer. This fragment has previously been suggested to retain the major enhancing activity. Surprisingly, no or only minor differences were discovered when the footprints obtained with B-cell extracts were compared with those obtained with HeLa cell and T-cell extracts. Intriguingly, two factors binding specifically to different sequences of the IgH enhancer are shared by polyoma as well as Moloney sarcoma virus (MSV) and lymphotropic papova virus (LPV) enhancer, respectively. All three of these enhancer elements exhibit altered cell type specificities. This indicates the utilization of similar or identical factors for transcriptional enhancement in different cell types. A cassette model consisting of different factor binding sites will be discussed. PMID- 3102228 TI - Evidence for two extracellular domains in the human interleukin-2 receptor: localization of IL-2 binding. AB - The human interleukin-2 (IL-2) receptor was quantitatively cleaved into two large disulfide-bonded fragments by either trypsin or endoproteinase lys-C (endo lys C). The smaller fragment contains both N-linked oligosaccharides found in the intact receptor and is derived from the amino terminus of the molecule. The larger proteolytic fragment was metabolically labeled with 32PO4 and represents the carboxy terminus. The predicted cleavage sites of both enzymes lie in the region of the molecule encoded by exon 3. This pattern of limited proteolysis provides biochemical evidence that the extracellular region of the receptor is organized into two domains. This supports a structural model of the receptor in which the regions of internal homology encoded by exons 2 and 4 form independent disulfide-bonded domains connected by a hydrophilic segment. To determine the role of these domains in IL-2 binding, [125I]IL-2 was chemically cross-linked to the proteolytically cleaved receptor on the cell surface. The 125I-labeled complex obtained displayed N-linked oligosaccharides and had an Mr consistent with one molecule of IL-2 cross-linked to the smaller proteolytic fragment of the receptor. Thus, the amino-terminal domain of the IL-2 receptor appears to form an integral part of the IL-2 binding site. PMID- 3102229 TI - Role of G-proteins in T cell activation: non-hydrolysable GTP analogues induce early ornithine decarboxylase activity in human T lymphocytes. AB - Rapid activation of ornithine decarboxylase is one of the earliest recognized events during induction of a mitogenic response in human T lymphocytes. Here we show that the non-hydrolysable GTP analogues guanine-5-(gamma-thio)trisphosphate and guanylyl-5-imidodiphosphate, introduced into human T cells by means of a transient membrane permeabilization technique, can replace an external mitogenic ligand, such as concanavalin A, in inducing early ornithine decarboxylase activity. Neomycin inhibits this rapid activation at concentrations known to bind to phosphoinositides. One of the two compounds formed in polyphosphoinositide breakdown, inositol-1,4,5-trisphosphate, also induces ornithine decarboxylase activity. The other, diacylglycerol, apparently does not, since the phorbol ester, tetradecanoyl phorbol acetate, which is thought to mimic the action of diacylglycerols, does not alter basal ornithine decarboxylase activity in T cells until several hours after administration. These findings indicate that guanine nucleotide-binding regulatory (G-) protein(s) participates in the transduction of the mitogenic signal. The intracellular target system for this G-protein may include phosphoinositide breakdown and generation of inositoltrisphosphate, which might be involved in the early activation of ornithine decarboxylase. PMID- 3102230 TI - Regulated splicing produces different forms of dopa decarboxylase in the central nervous system and hypoderm of Drosophila melanogaster. AB - The dopa decarboxylase gene (Ddc) of Drosophila melanogaster is expressed in the hypoderm and the nervous system and promoter elements mediating differential expression in these tissues have been identified (Scholnick et al., 1986). Here we report an additional mode of regulation; the unique primary transcript of the Ddc gene is spliced to form mRNAs in these two tissues which differ by a single internal exon. In vitro mutagenesis and P-element-mediated transformation were employed to manipulate the tissue-specific expression of these RNAs. This approach demonstrated that regulated splicing rather than differential stability causes the tissue-specific expression of these RNAs and allowed the identification of Ddc enzyme isoforms encoded by each mRNA. The Ddc enzyme in the central nervous system differs from the hypodermal Ddc protein by the addition of 33-35 amino acids on the N terminus. PMID- 3102231 TI - Sequence of carbonic anhydrase II cDNA from chick retina. AB - Sequences of three cDNA clones for carbonic anhydrase II (CA-II) from chick retina are presented. The longest cDNA clone encodes all but the first three amino acids of CA-II, and the encoded sequence generally agrees with published fragments of CA-II sequence from chick red blood cells. It is 70% identical to human CA-II; the active-site residues are conserved, but the chick protein has six extra cysteines. There is a long 3'-untranslated region which contains a second open reading frame, but this is not conserved. There appears to be a single CA-II gene in the chick. Some anomalies in cDNA synthesis and in Bal31 deletion are noted. PMID- 3102232 TI - Protein synthesis in Drosophila melanogaster embryos. Purification and characterization of polypeptide chain-initiation factor 2. AB - Eukaryotic initiation factor 2 (elF-2) was purified from the high-salt wash fraction of Drosophila melanogaster embryos. This factor, with a molecular mass of about 90 kDa, consists of two subunits of 47 kDa and 39 kDa on dodecylsulfate/polyacrylamide gel electrophoresis. The 39-kDa subunit is phosphorylated by the hemin-controlled inhibitor of rabbit reticulocytes in a terminal fragment which can be cleaved by mild treatment with trypsin. Drosophila elF-2 is not a substrate for protein kinases capable of phosphorylating the beta subunit of elF-2 from rabbit reticulocytes. It is also shown that Drosophila elF 2 can form a ternary complex with GTP and Met-tRNAi, which can be efficiently transferred to 40S ribosomes in the presence of AUG and Mg2+. This factor is able to form a binary complex with GDP. Furthermore, purified elF-2 contains about 0.3 mol bound GDP/mol suggesting a high affinity of the factor for this nucleotide. Data supporting the notion that this affinity is increased in the presence of Mg2+, which impairs the GDP/GTP exchange on elF-2, are presented. The properties of Drosophila elF-2 suggest that this factor may be susceptible to regulation by a mechanism like that operating on rabbit reticulocyte elF-2. PMID- 3102233 TI - Purification and partial characterization of lysosomal neuraminidase from human placenta. AB - Lysosomal neuraminidase and beta-galactosidase are present in a complex together with a 32-kDa protective protein. This complex has been purified and the different components have been dissociated using potassium isothiocyanate (KSCN) treatment. beta-Galactosidase remains catalytically active, but neuraminidase loses its activity upon dissociation. The inactive dissociated neuraminidase was purified by removing the remaining non-dissociated beta-galactosidase/protective protein complex using beta-galactosidase-specific affinity chromatography. The dissociated neuraminidase material shows two major polypeptides on SDS-PAGE with an apparent molecular mass of 76 kDa and 66 kDa. Subsequently the 32-kDa protective protein was dissociated from the beta-galactosidase/protective protein complex, and purified. Antibodies raised against the dissociated inactive neuraminidase preparation specifically immunoprecipitate the active neuraminidase present in the complex with beta-galactosidase and protective protein. By immunoblotting evidence is provided that the 76-kDa protein is a subunit of neuraminidase which, in association with the 32-kDa protective protein, is essential for neuraminidase activity. PMID- 3102234 TI - Autotrophic synthesis of activated acetic acid from CO2 in Methanobacterium thermoautotrophicum. Synthesis from tetrahydromethanopterin-bound C1 units and carbon monoxide. AB - The synthesis of acetyl-CoA from CO2, H2, and various C1 compounds was studied in vitro with extracts and with protein fractions of Methanobacterium thermoautotrophicum. Acetyl-CoA synthesis from CO2 and H2 by extracts required CO2 reduction to CH4 to proceed. Both processes were highly stimulated by formaldehyde which served as the carbon precursor of both CH4 and the CH3 group of acetate. Carbon monoxide in combination with formaldehyde dramatically stimulated the acetyl-CoA synthesis up to 150-fold. In this system, which did not require CO2 reduction to the formaldehyde and CO level, acetyl-CoA synthesis was no longer dependent on CH4 formation. The soluble (100,000 X g supernatant) cell protein was resolved into a protein fraction [45-60% (NH4)2SO4-fraction] which catalyzed acetyl-CoA synthesis at a specific rate of 15 nmol X min-1 X (equivalent of mg cell protein)-1 (60 degrees C). This oxygen-sensitive enzyme reaction required dithioerythritol for activity and was strictly dependent on coenzyme A, CO, and N5,N10-methylene tetrahydromethanopterin, N5-methyl tetrahydromethanopterin or formaldehyde plus tetrahydromethanopterin. The incorporation of formaldehyde is explained by the spontaneous formation of methylene tetrahydromethanopterin. The product of the reaction, acetyl-CoA, was quantitatively derived from CO (carboxyl of acetate) and a C1 derivative of tetrahydromethanopterin (methyl of acetate). The C1 derivative of tetrahydromethanopterin could not be replaced by a C1 derivative of tetrahydrofolate or by methyl-coenzyme M; ATP was not required. The active protein fraction contained CO dehydrogenase and at least on corrinoid protein. These results provide strong biochemical arguments for the proposed mechanism of autotrophic acetyl-CoA synthesis in Methanobacterium. PMID- 3102235 TI - Secretion of Bacillus subtilis levansucrase: a possible two-step mechanism. AB - The rate of exocellular levansucrase synthesis in an overproducing (sacUh) strain of Bacillus subtilis was shown to be directly proportional to the amount of two different transient forms of this enzyme located within the membrane fraction of the cells. The apparent Mr of the larger membrane form was 53,000, and that of the smaller form 50,000; the half-life time of each form was estimated in vivo to be 4-6 s and 32-42 s, respectively. Ethanol treatment of the cells lead to the accumulation of the 53,000-Mr form which may represent 1.5% of total membrane proteins. This latter form, partially purified, was transformed in vitro into the 50,000-Mr form by the action of the Escherichia coli leader peptidase. These enzyme forms were quite different from the exocellular levansucrase since they showed a weak affinity for hydroxyapatite and needed complexed iron to display enzyme activity. Assuming the membrane forms were precursors of exocellular levansucrase, we propose a two-step mechanism for the secretion process of levansucrase. The number of exoprotein synthesis/secretion sites in a B. subtilis cell is estimated to 2.5 X 10(4). PMID- 3102236 TI - Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate. AB - Strontium kinetics were investigated in a group of 14 patients receiving 89Sr palliation for metastatic bone disease secondary to prostatic carcinoma. Using 85Sr as a tracer, total body strontium retention R(t) was monitored for a 3 month period following 89Sr administration, and at 90 days was found to vary from 11% to 88% and to correlate closely with the fraction of the skeleton showing scintigraphic evidence of osteoblastic metastatic involvement. Strontium renal plasma clearance varied from 1.6 l/day to 11.6 l/day, and in nine patients was significantly reduced compared with values found in healthy adult men, probably due to increased renal tubular reabsorption associated with the disturbance of calcium homoeostasis. Renal clearance rate was the principal factor determining R(t) for t less than 6 days, and was an important secondary factor at later times. Over the interval 30 days less than t less than 90 days, R(t) was closely fitted by the power law function R(t) = R30 (t/30)-b, with R30 and b showing the close correlation expected from the effect of R(t) on strontium recycling. The correction of the data for this effect to determine the true skeletal release rate is described. Measurement of localized strontium turnover in individual metastatic deposits from whole body profiles and scintigraphic images gave retention curves that typically rose to a plateau by 10 days after therapy, and then decreased very slowly. In contrast, retention curves for adjacent normal trabecular bone showed more rapid turnover, peaking at 1 day and subsequently decreasing following a t-0.2 power law function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102237 TI - Metabolizable 111In chelate conjugated anti-idiotype monoclonal antibody for radioimmunodetection of lymphoma in mice. AB - The relative biological properties of 111In-labeled monoclonal antibodies (MoAb) coupled with a conventional bifunctional chelate (BC) and a new, enzyme metabolizable, bifunctional chelate (BCM) were investigated. A rat IgG2a MoAb against idiotype from a mouse B-cell lymphoma was utilized. Mice bearing B-cell lymphomas in the subcutaneous tissues of the flank were given IV-injections of labeled MoAb and imaged or killed for organ counting at 24 h or 48 h. Rat anti dinitrophenyl IgG2a MoAb and non-specific polyclonal mouse IgG were used as controls. Compared to BC, the use of BCM resulted in a substantial decrease in blood background activity, a shorter biological half-life and an increase in tumor to blood ratio at the expense of a moderate decrease in absolute tumor uptake. The versatile chemistry of these C-1 substituted bifunctional chelates provides a variety of possible enzyme cleavable moieties for further investigation. PMID- 3102239 TI - The pioneers of pediatric medicine: Otto Ullrich (1894-1957). PMID- 3102238 TI - A rat model system for radioimmunodetection of kappa myeloma antigen on malignant B cells. AB - A novel experimental model was established in normal rats for studying the localisation and tissue distribution of a murine monoclonal antibody directed against kappa light chain B cell malignancies. The antibody, K-1-21 was raised against human kappa Bence Jones Proteins and reacts with a cell membrane antigen KMA which is restricted to some kappa myeloma and lymphoma cells. In the rat model, kappa or lambda Bence Jones protein-conjugated sepharose was implanted subcutaneously on either flank 24 h before the injection of 131I-labelled K-1-21 or its F(ab')2 fragment. Gamma camera imaging and tissue distribution studies showed specific localisation of the K-1-21 antibody in the kappa sepharose. Injection of F(ab')2 antibody fragments resulted in faster background clearance, earlier delineation of the specific image and significantly higher target to blood ratios than those obtained with the intact antibody. These results suggest that the model may provide an alternative system to tumour xenograft bearing nude mice for studying localisation of antibodies with therapeutic potential. PMID- 3102240 TI - Pharmacokinetics of chlordesmethyldiazepam after single-dose oral administration in humans. AB - The pharmacokinetics of chlordemethyldiazepam--a pharmacologically very active new 1,4-benzodiazepine derivative--in healthy subjects after administration of a single oral dose of 2 mg, was studied. Peak concentrations were reached in 1.2 +/ 0.2 hours. Plasma levels declined with a biphasic pattern, and the elimination phase had a half-life of 82.9 +/- 14.1 hours. The concentrations of the main metabolite of chlordemethyldiazepam, lorazepam, were about 7% of those of the parent compound. In urine only conjugated lorazepam could be found its 96 hour excretion reaching about 15% of the administered dose of parent drug. PMID- 3102241 TI - Distilled water versus chemotherapeutic agents for transitional bladder carcinoma. AB - The effect of distilled water on exfoliated tumor cells from transitional bladder carcinoma was compared to the effect of chemotherapeutic agents dissolved in saline and in distilled water. The experiment was controlled by comparison to the effect of saline on cells under the same conditions. Distilled water proved as effective as chemotherapeutic agents in distilled water and more destructive than chemotherapeutic agents in saline within the 2-hour time limit of the experiment. PMID- 3102242 TI - Identity between human interferon-gamma and "macrophage-activating factor" produced by human T lymphocytes. AB - Human peripheral blood monocytes purified by counterflow elutriation were activated in vitro by human natural or recombinant interferon-gamma (IFN-gamma) as shown by enhanced killing of Listeria monocytogenes and increased production of H2O2 in response to phorbol myristate acetate. Half-maximal stimulation for macrophage activation (MAF) was observed with 10-20 antiviral U/ml of purified recombinant IFN-gamma. These MAF activities were found to correlate with the antiviral activity dependent on IFN-gamma under several experimental conditions. Both activities were recovered together from supernatants of concanavalin A stimulated peripheral blood mononuclear cells and in the media of a large number of T cell clones of different specificities. The parallelism between the two activities was also observed upon fractionation of culture media from producing cells and upon treatment of such preparations with low pH and high temperature. Finally, three antibodies with different specificities were found to abrogate the MAF and antiviral activities from lymphocyte culture supernatant. These results indicate that MAF released by stimulated lymphocytes is identical to IFN-gamma. PMID- 3102243 TI - Different human B cell subsets respond to interleukin 2 and to a high molecular weight B cell growth factor (BCGF). AB - After activation by anti-mu antibody human B cells acquire the ability to proliferate in the presence of recombinant interleukin 2 (IL 2), a 20-kDa mol. mass B cell growth factor (BCGF) and a high mol. mass BCGF (50-kDa BCGF). An anti IL 2 receptor (IL 2R) monoclonal antibody inhibits the IL 2-dependent proliferation without affecting that induced by BCGF. B cells expressing the IL 2R after anti-mu antibody activation (IL 2R+ cells) were separated from those not expressing IL 2R (IL 2R- cells). IL 2 stimulated the proliferation of only IL 2R+ cells whereas the 20-kDa BCGF acted on both IL 2R+ and IL 2R- cells. Importantly, the 50-kDa BCGF supported the proliferation of IL 2R- cells whereas it was inactive on IL 2R+ cells. Thus, the B cell subset responding to the 50-kDa BCGF after anti-mu antibody activation is distinct from that responding to IL 2. PMID- 3102244 TI - Human T cell clones can induce in vitro IgE synthesis in normal B cells regardless of alloantigen recognition or specificity for peculiar antigens. AB - A total number of 119 (98 CD 4+ and 21 CD 8+) T cell clones were established from tonsil and peripheral blood of three nonallergic individuals and examined for their ability to induce in vitro IgE synthesis in normal B cells. Following preactivation for 24 h with phytohemagglutinin, 34 clones (33 CD 4+ and 1 CD 8+) induced normal B cells to synthesize remarkable amounts of IgE in vitro. In contrast, equal numbers of T blasts of phytohemagglutinin-induced T cell lines obtained from unfractionated T lymphocyte suspensions of the same donors did not show such an effect. The in vitro IgE synthesis evoked by T cell clones was detectable between day 6 and 9 and peaked on day 12. Most clones maintained their ability to stimulate in vitro IgE synthesis in repeated assays over a 3-month period. The induction of IgE synthesis by cloned T cells did not reflect alloantigen recognition on target B cells, since T cell clones induced IgE synthesis in B cells from all randomly selected donors tested, including autologous B cells. Preincubation for 24 h with optimal stimulatory concentrations of anti-CD 3 (OKT 3) monoclonal antibody or its addition through the entire culture period also enabled T cell clones to stimulate de novo IgE synthesis in vitro in normal B cells. Virtually all the T cell clones active on IgE synthesis induced the in vitro production of remarkable amounts of IgM and IgG as well. These data indicate that several human T cell clones can induce normal B cells to synthesize immunoglobulin of different classes, including IgE, regardless of alloantigen recognition on target B cells or specificity for peculiar antigens. The activity of these clones was apparently mediated by triggering of the monomorphic molecular complex CD 3, immediately before or during the incubation of T cell clones with the target B cells. PMID- 3102245 TI - Activation of lymphokine genes during stimulation of cloned T cells. AB - To study the regulation of lymphokine production by T lymphocytes, we have characterized the activation of lymphokine genes in T cells by measuring the levels of lymphokine mRNA in cloned murine T lymphocytes after stimulation. Lymphokine mRNA was not detected in cells taken after seven days of maintenance culture. Following stimulation of T helper lymphocytes L2 and AD9.1 with concanavalin A, lymphokine mRNA appeared, reached peak levels and disappeared over a 43-h time period. A single stimulation event resulted in the induction of mRNA for interleukin 2 (IL 2), IL 3 and interferon gamma. Maximal mRNA levels were generally found at 6 h in the T helper lymphocytes, but could occur as late as 18 h. The lymphokine genes were expressed coordinately; however, in these cloned cells, IL 2 mRNA levels appeared to be lower than the other two mRNAs. Lymphokine titers in the supernatant fluids paralleled the appearance of mRNA but IL 2 titers began to fall after 12 h probably because of utilization of this lymphokine by the activated cells. In the cytolytic T lymphocyte, L3, qualitatively similar kinetics were found after stimulation by lectin or a clonotypic antibody with peak mRNA levels occurring later (18 h) with the antibody. These studies indicate a single stimulating event activates the lymphokine genes of T cells in a coordinate manner; the appearance of the lymphokines in supernatant fluids represents de novo synthesis of these proteins but the levels of lymphokines measured in supernatant fluids reflects both production and utilization rates, and exposure to IL 2 at the time of stimulation is not essential for the production of other lymphokines. PMID- 3102246 TI - Function of the LFA-1 and T4 molecules in the direct activation of resting human B lymphocytes by T lymphocytes. AB - Activated T lymphocytes can provide all of the signals necessary to induce the proliferation of resting B lymphocytes. The activation signal is presumably initiated through direct T-B lymphocyte contact. The role of the leukocyte function antigen-1 (LFA-1) and T4 molecules in the activation of purified, small B lymphocytes by mitomycin C-treated T lymphocytes was examined by using monoclonal antibodies that react with and inhibit the function of these molecules. Anti-LFA-1 antibody binding significantly inhibited T-B lymphocyte interactions that result in B lymphocyte proliferation. In contrast, the presence of anti-T4 antibodies at concentrations as high as 100 micrograms/ml did not inhibit this interaction. These results indicate that the B lymphocyte activation signal may not be mediated through the interaction of T4 molecules with major histocompatibility complex class II antigens of the B lymphocyte but is a cell cell contact-dependent event that is facilitated by LFA-1 molecules. PMID- 3102247 TI - A specific serine proteinase is inducible in Lyt-2+,L3T4- and Lyt-2-,L3T4+ T cells in vitro but is mainly associated with Lyt-2+,L3T4- effector cells in vivo. AB - Recently, we and others reported on the expression of a serine proteinase in long term cultured murine T lymphocyte cell lines. In an attempt to explore the distribution and possible regulation of this enzyme in T lymphocyte subsets, we performed the presented detailed study. We found that the proteinase is not expressed by thymocytes and resting T cells but can be induced by lectin or antigen in combination with lymphokine sources in vitro in macrophage-depleted unselected T cells as well as in both T cell subsets (Lyt-2+,L3T4- and Lyt-2 ,L3T4+) separated by flow cytofluorometry. Furthermore, it appears that cell associated proteinase activity is increasing with prolonged culture period of sensitized T lymphocytes and that it is higher in antigen-activated as compared to lectin-activated T cells. When tested for substrate specificity the T cell associated proteinase was shown to preferentially cleave model peptide substrates carrying L-arginine at position P1 in combination with nonpolar amino acids at position P2 and P3. As concluded from its sensitivity to proteinase inhibitors the enzyme can be classified as a serine proteinase and by molecular sieving at high ionic strength it was shown to have a mol. mass of approximately 50-60 kDa. Analysis of in vivo activated T cells revealed that this particular proteinase was expressed in flow cytofluorometry sorted lymphocytic choriomeningitis virus specific Lyt-2+,L3T4- cytolytic T lymphocytes but not in Lyt-2-,L3T4+ T cells presensitized with either Listeria monocytogenes or I-A alloantigens. The data demonstrate that the two T cell subsets (Lyt-2+,L3T4-; Lyt-2-,L3T4+) have distinct in vitro induction requirements for the expression of proteinase and that after activation of T cells in vivo the enzyme is preferentially associated with Lyt-2+,L3T4- effector cells. PMID- 3102248 TI - B cell receptors for interleukin 2: demonstration of IL2 internalization and of complementary effects of lipopolysaccharide and phorbol diester on receptor expression. AB - We have previously shown (J. Exp. Med. 1984. 160: 1170) that murine B cells activated with lipopolysaccharide (LPS) and rabbit anti-mouse Ig antibodies together (LPS-RaMIg blasts) express high-affinity interleukin 2 receptors (IL 2R) and respond to IL 2. This is not the case for B cells activated with either LPS alone (LPS blasts) or anti-Ig alone. In the present study IL 2R function and expression were further investigated by using this model. First, it was found that LPS-RaMIg blasts internalize IL 2 in a time- and temperature-dependent manner very similar to that occurring in CTLL (T lineage) cells. LPS blasts, however, did not internalize IL 2. LPS blasts were found to express 12 times less binding sites for anti-IL 2R monoclonal antibody (PC 61 monovalent Fab) as compared to LPS-RaMIg blasts and at least 30 times less IL 2 binding sites of high as well as of lower affinity. Second, with regard to the requirements for receptor expression, it was observed that either anti-Ig or phorbol diester (phorbol-12-myristate 13-acetate) can induce IL 2R and IL 2 responsiveness (proliferation assay) in LPS blasts but not in fresh B cells. Taken together these results provide further evidence for the similarity of IL 2R function in activated B and T cells, confirm that surface-Ig cross-linkage and phorbol-12 myristate 13-acetate have similar effects on B cells and suggest that LPS on the one hand, and phorbol-12-myristate 13-acetate or anti-Ig on the other provide complementary signals necessary for IL 2R expression. PMID- 3102249 TI - T cell nature of some lymphokine-activated killer (LAK) cells. Frequency analysis of LAK precursors within human T cell populations and clonal analysis of LAK effector cells. AB - The cell lineage of the lymphokine-activated killer (LAK) cells has been reinvestigated. Both T and non-T cells, isolated on the basis of rosette formation with sheep erythrocytes (E), generated LAK activity after 3-4 days of culture in recombinant interleukin 2 (rIL 2) in 8 different individuals tested. By applying a microculture technique which allows clonal expansion of virtually all E rosetting T cells, we further analyzed the frequency of clonogenic LAK precursors within T cell populations. Approximately 1 of 25 T cells was found to be a LAK precursor. Moreover, microcultures with LAK activity lysed both the natural killer-sensitive K562 cell line and the P815 target cells in the presence of phytohemagglutinin (PHA). Since cytolytic T lymphocytes capable of lysing P815 cells in the PHA-dependent assay were approximately 1/3, it is evident that only a minor subset of cytolytic T lymphocyte precursors can acquire LAK activity even in the presence of large amounts of IL 2. Several LAK clones obtained by limiting dilution were further expanded and analyzed for their phenotypic and functional properties. Twelve out of 14 clones analyzed expressed the T3+ T11+ phenotype whereas 2 were T3- T11+. All had maintained their original cytolytic pattern; moreover, the large majority of the T3+ clones produced IL 2 and interferon-gamma following PHA stimulation. PMID- 3102250 TI - The use of hybrid hybridomas to target human cytotoxic T lymphocytes. AB - This study describes a general strategy to produce hybrid monoclonal antibodies that are capable of targeting human cytotoxic T lymphocytes (CTL) against any cell carrying the appropriate target antigen. This is done by fusing a HAT sensitive, G418-resistant anti-T3 hybridoma with immune spleen cells (or with other hybridomas) that produce antibodies against the desired target antigen. In the hybrid hybridomas the reassortment of Ig heavy and light chains results in the production of bifunctional antibody molecules. Because of their double specificity, these antibodies are able to bridge human CTL to target cells and trigger cytotoxic function. We have isolated several stable hybrid hybridomas in which one specificity is against T3 and one either against HLA antigens (class II, DC-1, A3), human Ig (IgM, IgE, kappa), Toxoplasma gondii or an ovary carcinoma-associated antigen. In all of these cases we show that culture supernatants can efficiently and specifically target any CTL clone against any target cell that possesses the relevant surface antigen recognized by the antibody. Furthermore, the killing requires as little as 0.1 ng/ml of antibody, occurs at effector to target ratios comparable to those used in conventional cytotoxic assays and does not affect bystander cells. Nonspecific killing of Fc receptor-positive cells can be avoided using F(ab')2 fragments. As an example, we show that it is possible to change the major histocompatibility complex class and allospecificity of a CTL clone and target CTL against non-major histocompatibility complex antigens such as Ig, parasites and tumor-associated antigens. PMID- 3102252 TI - Activation of cytotoxic activity in cultures of bone marrow-derived macrophages by indomethacin. AB - Indomethacin was tested for its ability to augment the cytotoxic capacity of cultured bone marrow-derived macrophages (M phi) against P815 and YAC-1 tumor cells. M phi were obtained from the bone marrow of C57BL/6 mice precultured for 10-14 days and were virtually 100 percent pure. By addition of indomethacin these cells were activated to kill tumor cells in a 4-h and 18-h Cr-release assay. Since indomethacin is a potent inhibitor of the cyclooxygenase system, M phi were treated with prostaglandin E2. This treatment partially reversed indomethacin induced cytotoxicity. Addition of other cyclooxygenase inhibitors such as acetyl salicylic-acid, diclofenac or carprofen also induced cytotoxicity in bone marrow derived M phi. In all experiments we failed to detect any production of interferon. Addition of anti-interferon did not alter the cytolytic capacities demonstrating that endogenously induced interferon was not relevant in this mechanism. Our data show that cyclooxygenase inhibitors induce cytolytic activity of murine M phi not only against a M phi target but also against YAC-1 cells usually considered to be targets for natural killer cells. PMID- 3102251 TI - Expression of Pgp-1 (or Ly24) by subpopulations of mouse thymocytes and activated peripheral T lymphocytes. AB - The expression of Pgp-1 (Ly24) by subpopulations of thymocytes was investigated and a subpopulation of Lyt-2-/L3T4-/J11d- thymocytes was identified which contained significant numbers (80%) of Pgp-1+ cells. Among freshly isolated lymph node T cells but not cortisone-resistant thymocytes, Pgp-1 expression was heterogeneous. Stimulation of T lymphocytes with either concanavalin A or the combination of phorbol myristate acetate plus calcium ionophore resulted in increased Pgp-1 expression which was found to be regulated independently of DNA synthesis and interleukin 2 receptor expression. T cells in the cerebrospinal fluid exudate of mice infected with lymphocytic choriomeningitis virus were also found to be Pgp-1+. PMID- 3102253 TI - Interferon-gamma induces expression of the interleukin 2 receptor gene in human monocytes. AB - Interferon-gamma induces surface expression of interleukin 2 (IL2) receptors on human monocytes and the monocytic cell line U937. Freshly prepared peripheral blood monocytes and U937 cells were found to lack detectable IL 2 mRNA, but exposure of these cells to interferon-gamma induced IL 2 receptor message at 6 h of culture. At least two IL 2 receptor transcripts were detected (3.5 and 1.5 kb) in both monocytes and U937 cells, similar in size to IL 2 receptor transcripts in activated T cells. These results show that interferon-gamma induces expression of the monocyte IL 2 receptor gene. PMID- 3102254 TI - Monoclonal BALB/c anti-progesterone antibodies use family IX variable region heavy chain genes. AB - Variable region nucleotide sequences and respective translated amino acid sequences for three heavy chains (DB3, 11/32 and 10/8) and two light chains (DB3 and 11/32) of monoclonal mouse IgG1 anti-progesterone antibodies have been determined by primer extension mRNA sequencing. The three VH regions exhibit the same rarely observed VH IX gene family and have greater than 88% homology between them. Two associated light chain sequences are 95% homologous and belong to the V kappa I group. The N-terminal twenty two amino acids of the kappa light chain of the third antibody 10/8 have been determined by automated protein sequencing and are identical to those of 11/32. Thus, these three monoclonal anti-progesterones derived from separate fusions all use VHIX-V kappa 1 gene combinations. PMID- 3102255 TI - Molecular analysis of the murine lupus-associated anti-self response: involvement of a large number of heavy and light chain variable region genes. AB - The mRNA encoding heavy and light chains of a hybridoma-derived monoclonal IgM, kappa anti-immunoglobulin (rheumatoid factor) and an IgG3, kappa anti-histone autoantibody from systemic lupus erythematosus and arthritis-prone MRL/Mp-lpr/lpr mice have been molecularly cloned, and the nucleotide sequences corresponding to their variable regions have been determined. To investigate whether autoantibodies with specificities frequently observed in lupus disease might share common structural components, the sequences obtained in this study have been compared with those of a monoclonal MRL/Mp-lpr/lpr IgM, kappa anti-DNA autoantibody previously analyzed in our laboratory (J. Exp. Med. 1985. 161: 805). The 3 immunoglobulins employed different heavy chain variable region (VH) genes belonging to the large J588 VH gene family, kappa light chain variable region (V kappa) genes from 3 different V kappa groups, and different diversity and joining segments. Our findings suggest that murine lupus-associated autoantibodies of different specificities do not have genetic components in common to signal their self-reactive nature and are encoded by a large number of immunoglobulin gene elements. PMID- 3102256 TI - PAF-acether-induced synthesis of prostacyclin by human endothelial cells. AB - Platelet activating factor, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF acether) is a potent platelet-stimulating agent formed by most circulating cells. Added to cultured human endothelial cells, PAF-acether induced a dose-dependent synthesis of 6-keto-PGF1 alpha, the major stable metabolite of prostacyclin (PGI2), with a maximal effect at 100 nM, a concentration equivalent to that which aggregates human platelets. No release of von Willebrand factor (vWF) was noted under the same conditions. The poorly active PAF-acether analogue, methoxy-PAF failed to stimulate 6-keto-PFG1 alpha synthesis and the PAF-acether antagonists 48740 RP, BN 52021 and Ro 19-3704, prevented the stimulatory effect of PAF acether. Methyl-carbamate-PAF, an equieffective analogue of PAF-acether on platelets, also stimulated 6-keto-PGF1 alpha production. After a first stimulation by PAF-acether or methyl-carbamate-PAF, no response was detected when endothelial cells were re-exposed to either agonist, indicating auto- and cross desensitization as described for other cells. Since PAF-acether stimulated [3H]arachidonate release from pre-labelled endothelial cells, our results suggest that it stimulates phospholipase activity, which accounts for the increased PGI2 synthesis. The auto- and cross-desensitization between PAF-acether and methyl carbamate-PAF, ineffectiveness of methoxy-PAF and inhibition by selective antagonists strongly suggest interaction with specific membrane receptors. PMID- 3102257 TI - Influence of some inhibitors of arachidonic acid metabolism on oxytocin contractions in the isolated testicular capsule of the rat. AB - Oxytocin (50-750 nM) contracted the isolated testicular capsule of the rat. Mepacrine, a phospholipase A2 inhibitor (3 X 10(-5) M) and the lipoxygenase inhibitor nordihydroguaiaretic acid (10(-5) M) inhibited this response whereas the cyclooxygenase inhibitor, diclofenac sodium (10(-5) M), and the thromboxane synthetase inhibitor imidazole (10(-5) M) did not. It appears that metabolites of arachidonic acid dependent on lipoxygenase are involved in the contractile response of the rat testicular capsule to oxytocin. PMID- 3102258 TI - Reversal of arachidonic acid-induced guinea-pig tracheal relaxation into contraction after epithelium removal. PMID- 3102259 TI - Periodic benzodiazepine antagonist administration prevents benzodiazepine withdrawal symptoms in primates. AB - Daily administration of diazepam (1.5 or 6 mg/kg) in Rhesus monkeys results in the progressive development of physical dependence, as evidenced by Ro15-1788 (5 mg/kg i.m.) precipitated withdrawal symptoms including retching, vomiting, face and limb tremors. Every third day administration of the benzodiazepine antagonist, Ro15-1788, during a similar period of continuous diazepam exposure, significantly decreases withdrawal behaviors. During the course of diazepam exposure (with or without periodic Ro15-1788 administration) effects of chronic diazepam on spontaneously elicited sedative and active behaviors were not altered. It is postulated that physical dependence reverts to a drug naive state after each exposure to the benzodiazepine antagonist. This treatment may represent a possible therapeutic approach for preventing the (time dependent) development of physical dependence and the accompanying severe withdrawal symptoms. PMID- 3102260 TI - Failure to detect 6-hydroxydopamine in rat striatum after the dopamine releasing drugs dexamphetamine, methylamphetamine and MPTP. AB - Large doses of dexamphetamine, methylamphetamine and MPTP failed to induce the formation of 6-hydroxydopamine (6-OHDA) in rat striatum. The potent dopamine (DA) releasing actions of these drugs and of the MPTP metabolite MPP+ were shown by intracerebral dialysis of DA in conscious rats but 6-OHDA was not detectable in the perfusates. Neurotoxic effects of these DA releasing drugs are therefore probably not due, as previously suggested, to 6-OHDA formation and its subsequent uptake into nerve terminals. PMID- 3102261 TI - Serotonin receptors in the rat nucleus tractus solitarii and cardiovascular regulation. AB - The effects of local application in the nucleus tractus solitarii of different serotonin receptor agonists and antagonists were investigated in anesthesized rats. Unilateral microinjection of serotonin produced an acute and transient hypotension and bradycardia which could be totally blocked by antagonists acting preferentially upon 5-HT2 receptor binding sites: ketanserin and ritanserin. 5 HT1 receptor agonists such as RU-24969 and 8-hydroxy-2-(di-n-propylamino)tetralin failed to reproduce the acute cardiovascular effects of serotonin. Bilateral microinjection of 5-HT2 receptor antagonists produced an increase in the level and in the variability of arterial pressure but did not block the baroreceptor reflex arc. The data suggest that serotonin acting upon 5-HT2 receptors in the nucleus tractus solitarii plays an important role in the modulation of arterial pressure. PMID- 3102262 TI - Free Ca2+ requirements of agonist-induced thromboxane A2 synthesis in human platelets. AB - In quin2-loaded human platelets ionomycin raised cytosolic free calcium to greater than 1 microM and generated less than 1 ng thromboxane. Collagen alone or in the presence of EPO92 generated up to 32 and 16 ng thromboxane respectively; in the latter case at calcium levels around 120 nM. Thrombin maximally raised calcium to greater than 1 microM and generated up to 27 ng thromboxane, although in the presence of 1 mM EGTA these calcium and thromboxane levels were reduced to 200 nM and 5 ng respectively. PMID- 3102263 TI - The TRH test in rats with chronic Chagas disease. AB - TRH was studied in rats with chronic Chagas disease. It was found an increased secretion of TSH 60 minutes after intraperitoneal injection of the hypothalamic hormone. T3 and T4 were also decreased in basal conditions. This may indicate a primary hypothyroidism. PMID- 3102264 TI - The inability of oxytocin to influence the secretion of testosterone, prolactin, luteinizing and follicle-stimulating hormone in normal men. AB - Recently controversial data has been obtained about the endocrine effects of the neurohypophyseal hormone oxytocin both in vitro and in vivo. We measured testosterone, prolactin, LH and FSH by specific radioimmunoassay in seven healthy adult males before, during and after intravenous infusion of either synthetic oxytocin (4IU/100 ml/120 min) or saline. The findings clearly demonstrate that in men oxytocin does not affect plasma prolactin, LH and FSH. Our results do not establish an effect of oxytocin on basal testosterone release in healthy male subjects. PMID- 3102265 TI - The effect of 6-hydroxydopamine infusion into the third cerebral ventricle on the plasma prolactin levels in anoestrous ewes subjected to prolonged and repeated stress. AB - The effect of 6-hydroxydopamine (6-OHDA) infusion into the third cerebral ventricle on the secretion pattern of prolactin in anoestrous sheep, subjected to repeated and prolonged stress-stimuli was followed. On the 12-15 th day after the infusion of 6-OHDA into the third cerebral ventricle and after having tested the effect of this infusion on plasma prolactin concentration, the animals were subjected to mild electric footshocks 9 hrs daily (9 a.m.-6 p.m.) for 3 consecutive days. Infusion of 6-OHDA induced a very high rise of plasma prolactin values by about 3 times as compared to those found before infusion (from 118.2 +/ 39.5 to 338.9 +/- 81.7 ng/ml mesor 24 h). On the other hand, the response of the animals pretreated with 6-OHDA to electric stimulation was characterized by the lack of changes in plasma prolactin concentration; their plasma hormone concentrations were neither raised during stimulation nor decreased after the stimulation and were maintained during all these days nearly at the same level as after the infusion of 6-OHDA. Central mechanisms which could account for the so high and prolonged elevation of plasma prolactin concentration after the infusion of 6-OHDA and for the lack of its rise under conditions of prolonged stress are discussed. PMID- 3102266 TI - Induction of the pyridine nucleotide synthesis pathway in mitogen-stimulated human T-lymphocytes. AB - Mitogen stimulation of purified human T-lymphocytes with the phorbol ester 12-O tetradecanoyl, phorbol-13-acetate (TPA) and a monoclonal antibody to the T3 cell surface antigen caused a 6-11-fold increase in cellular levels of poly(ADP ribose) polymerase, a 6-20-fold amplification of cellular NAD+ levels and a 3-21 fold increase in NADP+ levels. Treatment of the cells with a combination of the two mitogenic signals also caused a 5-20-fold increase in NMN pyrophosphorylase activity, a 3-14-fold increase in ATP-NMN adenylyl transferase activity, and a 5 13-fold increase in NAD kinase activity. This is the first report showing induction of these three enzymes as part of the mitogenic response in purified human T-lymphocytes. Maximum increases in activity of each of these three enzymes required the combined presence of TPA and monoclonal antibody to human T-cell T3 antigen anti-T3. Analysis of the relative enzyme levels indicates that NMN pyrophosphorylase is the rate-limiting enzyme for NAD synthesis and NAD kinase is the rate-limiting enzyme for NADP synthesis. PMID- 3102268 TI - Restimulation of cell cycle progression by hypoxic tumour cells with deoxynucleosides requires ppm oxygen tension. AB - Continuous exposure of Ehrlich ascites tumour cells to argon-CO2 under in vitro conditions caused rapid cessation of cell proliferation. On fixing the O2 level at 10 ppm in the protective atmosphere (0.001% in comparison with about 20% in normoxic atmosphere), G1 and early S cells remained stationary while G2 cells continued to pass from G2 into mitosis, to remain in a non-growing state in G1 of the subsequent cycle. Re-aeration of cells following 12 h hypoxia induced up to 25% of the population to continue DNA synthesis without a preceding cell division, as revealed by flow-cytometric analysis. Supplementation of cells cultured under hypoxia with a combination of deoxynucleosides (100 microM deoxycytidine, 10 microM deoxyadenosine, 10 microM deoxyguanosine) was found to stimulate reprogression through the cycle, provided the residual oxygen tension in the protective atmosphere exceeded 40 ppm. The increase in the number of cells with a DNA content of more than 4 C and in the number of binucleate cells observed after re-aeration of hypoxic cells was not prevented by deoxynucleosides or by uridine, which were present in the medium either during hypoxia of from the beginning of reoxygenation. These results indicate that the development of polyploidy as a result of oxygen deficiency cannot be influenced by improvement of RNA and DNA synthetic precursors. PMID- 3102267 TI - Effect of aphidicolin on Friend erythroleukemia cell maturation. AB - Aphidicolin, a specific and reversible inhibitor of DNA polymerase alpha, was examined as a potential tool to evaluate the relationship between proliferative and differentiative events in Friend erythroleukemia cell (FELC) maturation. Since FELC can be induced to differentiate along the erythrocytic pathway with a variety of inducing agents, the effects of aphidicolin were tested on proliferating FELC and cells which were induced to differentiate with the potent inducer, hexamethylene bisacetamide (HMBA). Exposure of FELC to aphidicolin resulted in unbalanced growth within 24 h, as reflected by abnormally large cells, compared with untreated cells. In the presence of 10 or 50 microM aphidicolin, 75-90% of cells became differentiated (benzidine+ cells) within 48 h, although by 72 h cells treated with aphidicolin were non-viable as determined by trypan blue staining. A wider range of aphidicolin concentrations was tested in an effort to determine the optimal concentration of aphidicolin that maximally induced differentiation with minimal loss of cell viability. Continuous exposure of FELC from 24-96 h with doses of aphidicolin ranging from 0.5 to 50 microM was more effective for differentiation induction than was short-term exposure (1, 2, 4, 12 h) to the drug, although 1 h of exposure significantly (p less than 0.01) increased differentiation (28.1 +/- 7.8%) compared with untreated cells (2.7 +/- 1.0%). When cells were treated with HMBA (5 mM) and aphidicolin (1, 5, 10 microM), in combination, aphidicolin shifted the time of onset of differentiation from 72 to 48 h, but did not act synergistically or additively with HMBA; nor was the induction effect of aphidicolin changed by HMBA. In contrast, suboptimal doses of aphidicolin (0.5 microM) in combination with HMBA (2.5 mM) produced an additive effect on FELC differentiation. In addition, [3H]thymidine experiments demonstrated that aphidicolin reversibly blocked FELC in S phase and at G1-S interface of the cell cycle. These results indicate that aphidicolin can induce the differentiation of FELC, and that a complete round of replicative DNA synthesis is not required for differentiation to occur. PMID- 3102269 TI - Appearance of plasminogen activator activity during a synchronous cycle of a rat adenocarcinoma cell line, PA-III. AB - A study of the appearance of plasminogen activators during the cell cycle of a rat prostate adenocarcinoma cell line, PA-III, was undertaken. After release from a hydroxyurea (HU) block, the length of the cell cycle was determined and found to be 20-25 h, with the S-G2-M portions comprising approx. 10-15 h and the G1 phase occurring over a similar 10-15-h period. Assays for tissue-like plasminogen activator (t-PA) and urokinase-like plasminogen activator (u-PA) in cell conditioned medium revealed an increased appearance of both enzymes shortly after the S phase of the cycle. The pattern of production of these activators remained the same under differing conditions of cell synchronization. PMID- 3102271 TI - Photostimulation of the HMP shunt in human retinal pigment epithelium. PMID- 3102270 TI - Prostaglandin synthesis and release from cultured human trabecular-meshwork cells and scleral fibroblasts. AB - Human trabecular-meshwork (HTM) cells in culture convert arachidonic acid to two products: PGE2 and 6-keto PGF1 alpha. Prostaglandin PGE2 was the major product of arachidonic-acid metabolism. The synthesis and release of PGE2 and 6-keto PGF1 alpha was inhibited by a 15-min pre-treatment with indomethacin (5 X 10(-6) M) or a 4-24-hr incubation with 10(-7) M dexamethasone. The effects of dexamethasone could be prevented by cycloheximide (0.5 micrograms ml-1), or actinomycin D (2 micrograms ml-1). Prostaglandin E2 synthesis and release by these HTM cells from two different individuals could be stimulated by bradykinin, arachidonic acid and the calcium ionophore, A23187. PMID- 3102273 TI - Recombinant human interferon alpha-2 and juvenile chronic myelogenous leukemia: cell receptor binding, enzymatic induction, and growth suppression in vitro. AB - Recombinant human leukocyte interferon (HuIFN alpha 2) was studied to determine its potential as a therapeutic agent for the lethal monocytic malignancy of infancy, juvenile chronic myelogenous leukemia (JCML). In sharp contrast to cell cultures of normal marrow, specimens from two patients with JCML yielded an excessive and rapid proliferation of monocyte-macrophage elements without growth factor in clonogenic assay and in liquid culture. Using IFN alpha 2 labeled with 125I, the characteristics of IFN binding to cultured JCML monocyte-macrophages and their receptor site numbers were determined. IFN binding to cells from both patients disclosed two components: a high-affinity of 120 and 430 sites/cell, and a lower affinity of 1230 and 2500 sites/cell, respectively. In control studies, normal blood mononuclear cells or tonsillar B-lymphocytes displayed only a high affinity component. Brief exposure of JCML cells to IFN alpha 2 in vitro resulted in a sharp increase in the IFN-induced enzyme 2-5A synthetase, indicating the ability of JCML cells to respond metabolically. Dose-response studies performed in a clonogenic assay showed a dose-dependent growth inhibition of JCML monocyte macrophage colonies using IFN alpha 2 at concentrations of 10(2)-10(5) U/ml. These studies provide new information on the biological characteristics of JCML malignant cells, and suggest that IFN may be useful for treatment of this disorder. PMID- 3102274 TI - Carrier testing strategy in haemophilia A using two polymorphic DNA probes of the factor VIII gene. PMID- 3102275 TI - Dose-duration effect of sodium cromoglycate aerosol in exercise-induced asthma. AB - The dose-duration effect of sodium cromoglycate given by metered dose aerosol was studied in nine patients with exercise-induced asthma. Exercise tests were carried out at 15, 135 and 255 min after placebo, sodium cromoglycate 2 mg, 10 mg and 20 mg. The protective effect and the duration of action were dose-related. The new metered dose aerosol delivering 5 mg of sodium cromoglycate per actuation allows greater flexibility in adjusting the dosage and frequency of administration for individual patients. PMID- 3102272 TI - Turnover of palmitate, arachidonate and glycerol in phospholipids of rat rod outer segments. AB - Rat retinas were intravitreally labeled with [3H]palmitic acid, [3H]arachidonic acid or [3H]glycerol to study the turnover of the component parts of the major phospholipids in rod outer segments at times ranging from 2 hr to 12 days post injection. Rod outer-segment and retinal debris fractions were extracted and the major phospholipids separated by two-dimensional thin-layer chromatography. In darkness, [3H]glycerol rapidly labeled phosphatidylinositol in both rod outer segment and retinal debris fractions. The label in phosphatidylinositol subsequently decreased dramatically, demonstrating a rapid turnover of phosphatidylinositol with a half-life of less than 1 day. Phosphatidylcholine and phosphatidylethanolamine were maximally labeled by glycerol in the retinal debris at the 2-hr time-point and were maximally labeled in rod outer segments between 1 and 5 days post injection, with somewhat longer residence times in the rod outer segments. Phosphatidylserine showed a lag in initial labeling in both rod outer segment and retinal debris fractions indicating that this phospholipid is not a major precursor of phosphatidylcholine and phosphatidylethanolamine in rat retinas. [3H]Palmitate and [3H]arachidonate labels were rapidly incorporated into outer-segment phospholipids by 1-2 hr post injection. Eighty per cent of the palmitate label was initially associated with phosphatidylcholine at 2 hr. The total amount of palmitate label in rod outer-segment phosphatidylcholine did not change for 12 days post injection. Outer-segment phosphatidylethanolamine steadily increased in palmitate label throughout the 12-day period, suggesting that phosphatidylethanolamine may be utilized for recapture of palmitate released from breakdown of palmitate esters of rhodopsin or vitamin A or from phospholipids. Arachidonate primarily labeled phosphatidylinositol and phosphatidylcholine of both rod outer segments and retinal debris. The arachidonate label did not decrease dramatically during the first day in phosphatidylinositol as did the glycerol label, indicating that arachidonic acid is reutilized by the retina. Turnover of the individual phospholipids, as measured by a decrease in glycerol labeling of the phospholipid backbone, is more rapid than the loss of palmitate label, indicating that there is extensive reutilization of palmitate in both phosphatidylcholine and phosphatidylethanolamine of the rod outer segment. The data indicate that palmitate derived from many sources could be used by the photoreceptor to acylate rhodopsin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3102276 TI - Hypocapnic hyperventilation versus isocapnic hyperventilation with ambient air or with dry air in asthmatics. AB - The effects of three types of hyperventilation challenge tests (free hypocapnic, ambient air; controlled isocapnic, ambient air; controlled isocapnic, dry air), on FEV1 and on Raw were compared in 12 asymptomatic asthmatics. Controlled isocapnic hyperventilation of dry air as well as of ambient air caused bronchoconstriction lasting for more than 8 min, but the degree of bronchoconstriction was significantly greater with the former. Free hypocapnic hyperventilation of ambient air caused peak bronchoconstriction after 1 min, followed by a steady functional improvement; the values after 1 min were similar to those following isocapnic dry air hyperventilation, and values after 8 and 15 min were similar to those following isocapnic ambient air hyperventilation. The changes in Raw induced by the three types of hyperventilation were not influenced by a preceding full inspiration. In the eight subjects in whom the lung function had returned to within 10% of control after 30 min, identical duplicate hyperventilation challenge tests performed at that time demonstrated a significant, partial refractoriness for all tests. Thus the simple, free hypocapnic, hyperventilation test with ambient air was found to be as reliable as the more sophisticated controlled isocapnic tests. PMID- 3102277 TI - Improved procedure for simultaneous determination of sodium valproate and ethosuximide in serum by gas liquid chromatography. PMID- 3102278 TI - [10 years of using ftorafur in antitumor chemotherapy]. AB - The experience with ftorafur therapy of tumors of different localization was summarized. Ftorafur was shown to produce relatively few toxic side effects. PMID- 3102279 TI - An integrated prediction of secondary, tertiary and quaternary structure of glucose dehydrogenase. AB - Based on homology of partial sequences, on physico-chemical evidence and on studies using chemical modification, we came to the tentative conclusion that tetrameric glucose dehydrogenases from Bacillus megaterium and B. subtilis should have a structure closely related to that of lactate dehydrogenase. The overall homology of primary structures was found to be very low, however, and independent predictions of secondary structure produced a clearly different pattern of beta strands and alpha-helices. We nevertheless tried a manual prediction based on the hydrophobic nature of internal beta-sheet and on the amphiphilic character of external helices. This treatment led to the identification of analogues of all the beta-strands present in lactate dehydrogenase with the exception of beta C. Six amphiphilic helices were identified corresponding to alpha B, alpha C, alpha D, alpha 1F, alpha 2F and alpha 3G in lactate dehydrogenase. Conserved functional residues were found at analogous positions. The Q and R intersubunit contacts could be identified and partial proteolysis was found to occur on the outer surface of the tetramer. The structure was found to explain the better binding of NADP as compared to NAD+ and offered a rationalization of the role of the essential lysine at position 201. PMID- 3102280 TI - Conformational responses of an arachidonate- and U46619-binding haemoprotein in relation to platelet activation. AB - Antibodies were raised, in rabbits, against an arachidonate- and U46619-binding protein purified from calf platelets. Spectral measurements and immunodiffusion experiments were employed to follow conformational responses of the protein in relation to platelet activation. Upon treatment with the platelet agonists, arachidonate and PGH2, as well as the common haem ligands, imidazole and CN-, the purified protein had its Soret band red-shifted, with hypochromicity, but the protein saturated with the agonists, not with the haem ligands, showed altered antigenic properties in immunodiffusion experiments. In an analogous manner activation of gel-filtered calf platelets with high concentrations of ADP and A23187, as well as by cold, had Soret bands of extracts of sonicated platelets red-shifted, with hypochromicity; concomitantly, antigenically different conformations of the protein appeared in Triton X-100 extracts of the activated platelets. A protein immunologically related to the platelet protein was detected in Triton X-100 extracts of calf neutrophils. It is suggested that conformational changes of the protein induced by arachidonate or prostaglandin endoperoxides or H2O2 formed in different compartments during platelet activation by different stimuli may be a biochemical mechanism of stimulus-response coupling and that similar mechanisms might operate in other cell types. PMID- 3102281 TI - Biochemical and histological evidence that carcinoma of the prostate is associated with increased bone resorption. AB - We have investigated the hypothesis that carcinoma of the prostate with skeletal metastases is associated with increased bone resorption. In 54 affected patients a close correlation was observed between serum activity of alkaline phosphatase and urinary excretion of hydroxyproline (r = +0.818; P less than 0.001), comparable to that seen in Paget's disease of bone. The administration of synthetic salmon calcitonin (100 U subcutaneously) induced a significant fall in serum calcium and urinary excretion of hydroxyproline, proportional to the prevailing rate of bone turnover, as assessed by serum alkaline phosphatase or hydroxyprolinuria. Administration of the diphosphonate, etidronate, also decreased hydroxyprolinuria, suggesting that urinary hydroxyproline reflected increased rates of bone resorption in this disorder. Histology of bone in sites adjacent to and distant from skeletal metastases showed increased histological indices of bone resorption. These results suggest that the skeletal disease associated with prostatic carcinoma is characterized by generalized increases in bone resorption as well as focal increases in bone formation. PMID- 3102282 TI - Use of intranasal luteinizing hormone-releasing hormone agonist in uterine leiomyomas. AB - Nine women harboring uterine leiomyomas have been treated with subcutaneous injections and then with intranasal insufflation of luteinizing hormone-releasing hormone agonist for a total treatment period of 6 months. After initial stimulation, mean serum estradiol progressively decreased and stabilized at 36.8 +/- 4.9 pg/ml for the rest of the treatment period. The volume of uterine leiomyomas has been reduced by an average of 71%. Side effects and hot flushes were less severe and better tolerated than reported after sole subcutaneous administration. PMID- 3102284 TI - Luteinizing hormone bioactivity in human menopausal gonadotropin/human chorionic gonadotropin-induced cycles. AB - Eight human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) induced cycles in four anovulatory women unresponsive to clomiphene citrate plus hCG were studied. Blood samples were obtained for baseline determinations and daily thereafter, 24 hours after the injection of hMG. Serum estradiol (E2), progesterone, follicle-stimulating hormone, and luteinizing hormone (LH) were measured by radioimmunoassay. Bioassayable LH (LH-b) was determined by the immature mice interstitial cell in vitro bioassay for testosterone with LER-907 as the reference standard. Appropriate follicular growth, assessed by pelvic ultrasonography, occurred in all cycles. During induction days mean immunoassayable LH (LH-i) and LH-b levels were suppressed until the E2 concentrations rose to a mean of 1420.5 +/- 149 pg/ml (standard error of the mean), at which time a concurrent rise in LH-b and LH-i levels was observed (130% and 34%, respectively). LH-b/LH-i ratio increased by 63% on the day E2 peaked, indicating enhanced LH bioactivity before hCG administration. Our data suggest that during hMG/hCG-induced cycles, in a high E2 milieu, endogenous or exogenous LH may show a heterogeneity in its molecular content, resulting in enhanced bioactivity relative to immunoactivity. PMID- 3102283 TI - Periovulatory 17 beta-estradiol pattern in conceptional and nonconceptional cycles during menotropin treatment of anovulatory infertility. AB - The value of multiple parameters in the prediction of fertile cycles was prospectively evaluated in 52 menotropin-induced cycles. The periovulatory pattern of estradiol (E2) was found to correlate with conceptional cycles. E2 levels greater than 500 pg/ml on the day of human chorionic gonadotropin administration (day 0) with a further increase on day +1 (high ascending pattern- A1) were found to have a 51% predictive value for fertile cycles. Twelve of the 17 fertile cycles had an A1, type of response (71%), whereas the overall incidence of an A1 pattern was 42% (22 of 52). No pregnancies have occurred with preovulatory follicles less than or equal to 14 mm in diameter. The number of preovulatory follicles, E2 level on day 0, and midluteal progesterone had no predictive value for fertile cycles. PMID- 3102285 TI - Studies on the measurement and pharmacodynamics of human follicle-stimulating hormone. AB - The levels of immunoreactive follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), cortisol, and estradiol (E2) have been determined in serial samples of peripheral plasma from four subjects during the continuous, subcutaneous administration of Buserelin (Hoechst [UK] Ltd., Hounslow, UK) (250 micrograms/day) and after the intramuscular injection of purified, urinary FSH (Metrodin, Serono Laboratories [UK] Ltd., Welwyn Garden City, UK) (150 IU). During Buserelin administration the geometric mean levels of FSH and LH as measured by immunoradiometric assay were reduced by 87% and 37%, respectively, when compared with the corresponding values for days 1 and 2 of the menstrual cycle. After the intramuscular injection of FSH, peak levels (from 3.4 to 6.2 IU/l) occurred in peripheral plasma between 6 and 18 hours later. The levels were significantly elevated after 72 hours (P less than 0.01, Student's paired t test). There was no obvious effect of the drugs on the circadian rhythms of plasma PRL or cortisol, and no significant effect on the circulatory levels of LH or E2. PMID- 3102286 TI - Relationships between polypronuclear fertilization and follicular fluid hormones in gonadotropin-treated women. AB - Similar incidences of congenital abnormalities in in vitro fertilization and embryo transfer (IVF-ET) pregnancies and births in the general population have not supported earlier concerns that IVF may increase chromosomal aberrations. Nevertheless, polypronuclear fertilization is a common, undesirable, and poorly understood outcome of IVF. We evaluated hormone levels in 20 follicular fluids that were associated with mature oocytes that have fertilized abnormally (greater than or equal to pronuclei) and compared them to follicles with mature oocytes that cleaved normally, fertilized but failed to cleave, or did not fertilize. Progesterone (P), androstenedione, estradiol, percent free estradiol, sex hormone binding globulin, insulin, and prolactin were measured. P levels were significantly higher in follicular fluids associated with oocytes that fertilized abnormally than in the other groups. Levels of the other hormones were similar in all the study groups. We conclude that IVF of oocytes from highly luteinized follicles as judged by P levels may result in polypronuclear fertilization. PMID- 3102287 TI - Dibromochloropropane (DBCP): an 8-year reevaluation of testicular function and reproductive performance. AB - The current study summarizes an 8-year reassessment of testicular function and reproductive performance in 15 workers with dibromochloropropane (DBCP)-induced azoospermia and oligozoospermia. Recovery of spermatogenesis was observed in four oligozoospermic and three azoospermic men whose plasma follicle-stimulating hormone (FSH) concentration was normal during the whole period. A marked increase in FSH and luteinizing hormone concentrations above the upper limit of normal was found in the azoospermic workers who did not recover. No significant changes in FSH concentrations were detected in both recovered and nonrecovered oligozoospermic men. Testosterone levels of all patients were normal at all times. Paternal exposure to DBCP was not associated with increased risk of fetal malformations or spontaneous abortion. PMID- 3102288 TI - Simultaneous measurement of seminal L-carnitine, alpha,1-4-glucosidase, and glycerylphosphorylcholine in azoospermic and oligozoospermic patients. AB - L-carnitine, alpha,1-4-glucosidase, and glycerylphosphorylcholine were measured in seminal plasma of a selected group of azoospermic men and in an unselected group of oligozoospermic men. In vasectomized subjects the epididymal indices (mean +/- standard error: L-carnitine, 276.9 +/- 27.5 nmol/ejaculate; alpha glucosidase, 1.2 +/- 0.1 U/ejaculate; and glycerylphosphorylcholine, 1.5 +/- 0.2 mumol/ejaculate) were always below the normal range of fertile subjects (1757.4 +/- 76.7 nmol/ejaculate; 16.4 +/- 0.9 U/ejaculate; and 17.3 +/- 0.7 mumol/ejaculate, respectively). On the contrary in a large number of patients affected by azoospermia because of seminiferous tubular damage (750.4 +/- 83.6 nmol/ejaculate; 6.8 +/- 0.9 U/ejaculate; and 6.1 +/- 0.6 mumol/ejaculate; respectively) and in a few oligozoospermic subjects (1193.7 +/- 72.3 nmol/ejaculate; 10.3 +/- 0.7 U/ejaculate; and 10.8 +/- 0.7 mumol/ejaculate; respectively) the epididymal indices were found in the range of vasectomized subjects, showing an association between seminiferous tubular lesion and epididymal dysfunction. In conclusion, in spite of the low levels of epididymal indices found in patients with obstructive azoospermia, the presence of a large number of subjects with seminiferous tubular lesions without obstruction with similar low values of L-carnitine, alpha-glucosidase, and glycerylphosphorylcholine reduces the usefulness of these indices in differential diagnosis of azoospermia. PMID- 3102289 TI - In vitro fertilization: determination of follicular maturation for timing of human chorionic gonadotropin administration. AB - Hyperstimulation protocols for IVF require critical timing of hCG administration to complete follicular maturation. We studied 170 IVF cycles in 142 patients and retrospectively compared ultrasound and endocrine parameters in pregnancy cycles and spontaneous LH surge cycles with nonpregnancy, non-LH surge cycles. Twenty six of the 170 cycles resulted in a pregnancy (15.2%). Oocytes were recovered from 27 of 31 cycles in which a spontaneous LH surge occurred, and 9 of these cycles produced a pregnancy (33%). Follicle number and serum E2 on the day of ultrasound (cycle day 12 or 13) was lower in the LH surge group and pregnancy group than in the nonpregnant, non-LH surge group. In contrast, on the day of hCG administration or LH surge, serum E2 concentration per follicle greater than 1 cm in diameter was higher in the combined LH surge/pregnancy group (1219 pmol/l) than in the nonpregnancy/non-LH surge group (932 pmol/l). Our data suggest that it may be possible to individualize hCG administration at midcycle by determining the number of follicles greater than 1 cm by ultrasound on cycle day 12 or 13 and giving hCG when serum E2 levels reach 1100 to 1200 pmol/l per follicle. PMID- 3102290 TI - [Effect of prostaglandin E2 on the secretory function of the stomach]. AB - The effect of prostaglandin E2 (PgE2) injected with histamine in dogs with stomach fistula, involved a decrease of volume of secreted gastric juice, production of hydrochloric acid and pepsin lessening as compared with the findings obtained in the effect of histamine alone. The inhibition of gastric secretion increases in combined injection of PgE2 with histamine and acetylcholine. After intramuscular injection of PgE2 the content of sodium ions in the blood serum of rats decreases, the concentration of potassium becoming higher. In the mucose membrane of stomach the content of sodium and potassium increases; oxygen pressure in the mucous membrane of stomach decreases after the injection of PgE2. PMID- 3102291 TI - [Detection of anti-endomysium antibodies of the IgA type in the hamster esophagus]. PMID- 3102293 TI - Clomiphene citrate response is predictable in corpus luteum insufficiency. AB - In order to predict the correct dose of clomiphene citrate in corpus luteum insufficiency, the results of the treatment of 117 patients were evaluated. Serum progesterone and prolactin concentrations were determined by RIA. A 3-fold increase in serum progesterone concentration was found following the 100 mg per day clomiphene citrate treatment, independently of the pretreatment progesterone or prolactin values. This means that in a well-selected, hormonally homogeneous group of patients, contrary to earlier observations, the clomiphene citrate sensitivity of the patients is predictable. PMID- 3102292 TI - Effect of ouabain and bumetanide on the basal and the osmolality-affected prolactin secretion from human decidual cells in vitro. AB - Human decidual explants were incubated in vitro in media containing 10(-5) mol/l ouabain or 10(-4) mol/l ouabain or 0.5 X 10(-4) mol/l bumetanide to change the intracellular ionic concentrations. In isosmotic incubations (osmolality 315 mmol/kg), no significant effect of either 10(-5) mol/l ouabain or 0.5 X 10(-4) mol/l bumetanide was found on the decidual prolactin secretion (D-PRL-s). 10(-4) mol/l ouabain significantly decreased both decidual prolactin production and D PRL-s (P less than 0.05) and was therefore not used for the following cross-over experiments. Hyperosmotic media (387 mmol/kg) were produced by changing the concentration of either sodium chloride, potassium chloride, or mannitol. All increased D-PRL-s compared with the isosmotic media (315 mmol/kg). 10(-5) mol/l ouabain significantly diminished the increase otherwise elicited by the sodium chloride and the mannitol hyperosmotic media. However, in the hyperosmotic potassium chloride medium with 10(-5) mol/l ouabain, the D-PRL-s remained increased. The hyperosmotic medium (252 mmol/kg) reduced D-PRL-s compared with the isosmotic media (315 mmol/kg) and no significant effect of ouabain was found. Bumetanide did not change the D-PRL-s into any of the hypo- or hyperosmotic media compared with the secretion at 315 mmol/kg. Based on experience from other cell types, the results further indicate that the intracellular ionic concentrations could be of importance to the secretion of decidual prolactin in vitro. PMID- 3102294 TI - Quantitative comparison of Rh1 (Rho, D) antigen on D, Du and d red cells by radioimmunoassay using 125I-protein A. AB - Relative Rh1 (Rho, D) antigen contents of the red Rh: 1 (Rh positive, D), Rh: wl (Rh variant, Du) and Rh: -1 (Rh negative, d) cells were estimated from the quantity of 125I-protein A bound to the sensitized red cells. The isotope binding activity to both D and Du cells decreased in parallel with the dilution of anti-D serum. The relative amount of the 125I-protein A bound to Du cells was about one sixth that of D cells without papain treatment, while no isotope binding was observed in d cells. The Du red cells were quantitatively deficient in Rh1 (Rho, D) antigen activity compared with the D cells. A radioimmunoassay using 125I protein A was a very useful method for studies regarding measuring the relative amounts of various blood group antigens. PMID- 3102295 TI - Characterization of a timing mutant of Dictyostelium discoideum which exhibits "high frequency switching". AB - The preaggregative period of Dictyostelium discoideum is composed of two sequential rate-limiting components. The timing mutant FM-1 exhibits a decrease in the length of the preaggregative period and the interval between the maxifinger and early culminate II stage. In contrast, it is normal in all aspects of growth, in the sequence of morphogenetic stages, in spore formation, in the capacity to rapidly recapitulate morphogenesis, and in the erasure event and subsequent program of dedifferentiation. By the reciprocal shift experiment, it is demonstrated that FM-1 is completely missing the first of the two rate limiting components comprising the preaggregative period. The FM-1 mutation is heritable and behaves as a single mutation mapping to linkage group II. However, the FM-1 variant switches at relatively high frequency to several other timing phenotypes with longer preaggregative periods which in turn switch at high frequency. The FM-1 phenotype is considered in terms of timing regulation, and the process of high frequency switching between timing phenotypes is compared to other newly discovered switching systems. PMID- 3102296 TI - The ecdysoneless (ecd1ts) mutation disrupts ecdysteroid synthesis autonomously in the ring gland of Drosophila melanogaster. AB - Ring glands dissected from homozygous l(3)ecd1ts wandering larvae and upshifted in vitro to the restrictive temperature, 29 degrees C, synthesize abnormally low quantities of ecdysteroid. Nevertheless, ecd1 ring glands retain the ability to respond at 29 degrees C to an extract prepared from wild-type larval neural tissues that presumably contain prothoracicotropic hormone (PTTH), although both basal and stimulated levels of synthesis are lower than those in wild-type ring glands. Extracts prepared from ecd1 neural tissue exhibit an unusually high level of PTTH activity. Mutant ring glands downshifted in vitro to the permissive temperature after removal from larvae maintained at 29 degrees C regain the ability to produce normal basal and stimulated ecdysteroid levels. Collectively, these experiments demonstrate that the ecd1 mutation disrupts the physiology of the ring gland at 29 degrees C autonomously and may also interfere with PTTH release. PMID- 3102298 TI - Persistent impairment of insulin secretory response to glucose in adult rats after limited period of protein-calorie malnutrition early in life. AB - The effect of a limited period of protein-calorie malnutrition in young rats on glucose tolerance, insulin secretory response to glucose, and tissue composition in the adult was studied. Three-week-old rats were weaned onto semisynthetic diets containing either 5% protein (low protein; LP) or 15% protein (control; C) and maintained for 3 wk on their respective diets. At 6 wk of age all rats were returned to a commercial rat chow diet (18% protein). Glucose tolerance, insulin secretory response to glucose, and the protein/DNA ratio in liver, skeletal muscle, heart, kidney, small intestine, and lung were investigated at 3, 6, and 12 wk of age. Rats receiving LP diet failed to gain weight, but growth resumed immediately when they were transferred to commercial rat chow. They did not, however, catch up with C rats. Glucose tolerance and insulin secretory response to glucose remained similar between 3 and 12 wk in C rats. In 6-wk-old LP rats, glucose tolerance was impaired, and the insulin secretory response to glucose was absent. At 12 wk of age the glucose tolerance of the LP rats had normalized, but the insulin secretory response was still blunted. In 6-wk-old LP rats there was an inhibition of the age-dependent increase in cell size, shown by lowered protein/DNA ratios in all tissues studied. This decrease in cell size persisted at 12 wk in liver, skeletal muscle, heart, and lung. We conclude that protein calorie malnutrition early in life persistently impairs the insulin secretion. The persistently lowered protein/DNA ratios in many tissues may be related to this lowered capacity for insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102297 TI - Enhanced peripheral and splanchnic insulin sensitivity in NIDDM men after single bout of exercise. AB - We studied glucose metabolism in non-insulin-dependent diabetic (NIDDM) men with and without glycogen-depleting cycle exercise 12 h beforehand and have compared the results to our previous data in lean and obese subjects. Rates of total glucose utilization, glucose oxidation, nonoxidative glucose disposal (NOGD), glucose metabolic clearance rate (MCR), and endogenous glucose production (EGP) were determined with a "two-level" insulin-clamp technique (100-min infusions at 40 and 400 mU X m-2 X min-1) combined with indirect calorimetry and D-3 [3H]glucose infusion. Muscle biopsy specimens from vastus lateralis were analyzed for glycogen content and glycogen synthase activity before and after insulin infusions. After exercise, NIDDM subjects had muscle glycogen concentrations comparable with those of lean and obese subjects. The activation of glycogen synthase both by prior exercise and insulin infusion was similar to lean controls. After exercise, total glucose disposal was significantly increased during the 40-mU X m-2 X min-1 infusion (P less than .05), but the increase observed during the 400-mU X m-2 X min-1 infusion was not significant. These increases after exercise were the result of significantly higher NOGD during both levels of insulin infusion. The MCR of glucose during both insulin infusions was reduced in NIDDM compared with lean subjects but was very similar to that in obese nondiabetics. Basal EGP was significantly reduced on the morning after exercise (4.03 +/- 0.27 vs. 3.21 +/- 0.21 mg x kg-1 fat-free mass x min-1) (P less than .05) and associated with significant reductions of fasting plasma glucose (197 +/- 12 vs. 164 +/- 9 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102299 TI - Glyburide sensitizes perfused rat liver to insulin-induced suppression of glucose output. AB - Glyburide, a second-generation sulfonylurea, is used in the treatment of NIDDM because of its hypoglycemic action. However, the site and mechanism of action of this sulfonylurea remain unclear. We examined the ability of glyburide to enhance insulin's inhibitory effect on glucagon-stimulated hepatic glucose production. The livers of fed male rats were perfused with a Krebs-Henseleit buffer containing washed human red blood cells. After a 60-min control period during which the liver was exposed to both insulin and glucagon (10 microU/ml and 11 pg/ml, respectively), the glucagon concentration was increased to 88 pg/ml in the presence of 0, 10, 40, and 240 microU/ml of insulin. Hepatic glucose output and phosphorylase a activity were monitored during the control and elevated-glucagon periods. The glyburide-infused group received glyburide (1.6 microgram/ml) during both the control and elevated-glucagon periods. As expected, high levels of insulin suppressed glucagon-stimulated glucose production and phosphorylase activation. Insulin at a concentration of 10 microU/ml was unable to suppress glucagon's stimulation of glucose production or its activation of phosphorylase. However, in the presence of glyburide it was able to decrease stimulated hepatic glucose production and phosphorylase activation by 40 and 50% respectively. In the absence of insulin, glyburide was unable to suppress glucagon's glycogenolytic action, suggesting that the drug potentiates insulin's action on the liver rather than exerting an inhibitory effect directly. Insulin at a concentration of 240 microU/ml completely suppressed glucagon action, and glyburide had no additional effect. Therefore, glyburide is able to enhance the sensitivity of the perfused rat liver to insulin without altering maximal insulin responsiveness. PMID- 3102300 TI - Tolrestat, an aldose reductase inhibitor, prevents nerve dysfunction in conscious diabetic rats. AB - The effect of 4 wk of streptozocin (STZ)-induced diabetes on the transmission time of the auditory-evoked brain stem response (ABR) was examined in conscious male Sprague-Dawley rats. Distal nerve transmission time of the auditory pathway (latency of peak II), which includes conduction along the 8th cranial nerve, increased in diabetic rats (n = 9) relative to nondiabetic rats (n = 17). The difference in peak II latency between diabetic and control rats was significant beginning 2 wk after the induction of diabetes (P less than .05). In contrast, 4 wk of STZ-induced diabetes had no effect on the central transmission time of the auditory pathway (interpeak latency between peaks II and IV). Oral administration of tolrestat, a structurally novel aldose reductase inhibitor (n = 8; 20 mg/kg twice daily 1 wk before and 4 wk after STZ injection), prevented the diabetes induced increase in distal nerve transmission time. These findings indicate that experimentally induced diabetes can result in a nerve dysfunction as measured by the increased latencies of the early components of the ABR. Furthermore, because tolrestat prevents these changes in the ABR, aldose reductase and the polyol pathway are implicated in this neuropathy. PMID- 3102301 TI - Autoimmune diabetes in NOD mouse is L3T4 T-lymphocyte dependent. AB - Cultured BALB/c islets fail to function when transplanted into diabetic nonobese diabetic (NOD) mice; such grafted tissue is rapidly destroyed by disease recurrence. The cellular requirements for this graft damage are unclear. This study was designed to investigate the role of the L3T4+ T-lymphocyte subset in disease recurrence in the NOD mouse. L3T4+ T-lymphocytes were depleted by the in vivo administration of the L3T4-specific monoclonal antibody GK1.5. This treatment reduced the level of L3T4+ T-lymphocytes from an initial 43% of the peripheral blood lymphocytes to less than 4%. L3T4 levels remained at this low level for approximately 2 wk after withdrawal of GK1.5 treatment, after which the L3T4 levels slowly began to increase in the periphery. Grafting of cultured BALB/c islet tissue into GK1.5-treated diabetic NOD mice resulted in a rapid return to normoglycemia that persisted for 2-4 wk. The gradual return to the hyperglycemic condition roughly correlated with the reappearance of L3T4+ T lymphocytes in the peripheral circulation. From these findings we conclude that the disease process in the NOD mouse is L3T4 T-lymphocyte dependent. PMID- 3102302 TI - Preventive effect of monoclonal anti-L3T4 antibody on development of diabetes in NOD mice. AB - We analyzed the surface phenotypes of infiltrated cells in pancreases of nonobese diabetic (NOD) mice with monoclonal antibodies to mouse lymphocytes. Most of the infiltrated cells were Thy1+ and Ly1+ T-lymphocytes, and most of them were L3T4+ helper T-lymphocyte subsets. To elucidate the role of L3T4+ T-lymphocytes in the development of insulitis and diabetes in NOD mice, we treated the animals with injections of monoclonal anti-L3T4 antibody. Administration of this antibody prevented the insulitis and diabetes in NOD mice. These results lead to conclusions that the L3T4+ helper T-lymphocytes may play an essential role in the pathogenesis of type I diabetes and that the manipulation of the OKT4+ (Leu3+) T lymphocyte subset, the human homology of L3T4, with monoclonal antibodies may provide effective therapy for human type I diabetes. PMID- 3102303 TI - Rapid correction of wasting in children with cerebral palsy. AB - Severe cerebral palsy is often accompanied by wasting. The authors used standard methods for the correction of primary protein energy malnutrition in children with severe cerebral palsy. A randomised controlled trial was used to compare intensive nasogastric tube-feeding with the best oral feeding that could be achieved. Nasogastric feeding led to highly significant increases in weight. The changes in skinfold thickness and mid-arm muscle circumference indicated increases in both lean and fat tissue. This study indicates that wasting associated with cerebral palsy can be quickly corrected, so there is no reason why such patients should be exposed to the increased risks associated with wasting. PMID- 3102304 TI - Home monitoring of epilepsy. PMID- 3102305 TI - Production of crystallins and lens-like structures in differentiation-induced neoplastic pigment cells (goldfish erythrophoroma cells) in vitro. AB - We examined the crystallins present in lens-like cell aggregates produced by goldfish erythrophoroma (tumors of integumental erythrophores) cells in vitro using a combination of Sephadex-G-200 gel filtration, one- and two-dimensional sodium-dodecyl-sulfate/polyacryl-amide gel electrophoresis, immunoblotting, and indirect immunofluorescence assays. The two studied neoplastic pigment cell lines, GEM 81 and GEM 218, formed small, spherical, transparent cell aggregates, resembling lentoid bodies, within the cell mounds of monolayer cultures after treatment with dimethylsulfoxide (DMSO) and autologous serum. Partial purification of a water-soluble extract of such lens-like cell aggregates and subsequent immunoblotting using antibodies (polyclonal) against newt whole lens proteins revealed the presence of about 20 unequivocally conjugated peptides with molecular masses of 19-27 kilodaltons. From their antigenicity and their behavior during gel filtration and electrophoresis, most of these peptides were identified as either alpha- or beta-form crystallins. Immunofluorescence microscopy using antibodies to newt whole lens proteins revealed intense fluorescence in the lens like cell aggregates formed by these erythrophoroma cells, whereas the cell mounds in cultures of the same cell lines that had not been subjected to differentiation induction were almost unlabeled. Thus, goldfish erythrophoroma cells appear to be capable of crystallin production as well as the formation of lens-like cell aggregates upon the induction of differentiation. There is little available information indicating that normal pigment cells are capable of lens formation and crystallin synthesis during vertebrate ontogeny, and thus it is possible that neoplastic transformation of pigment cells is associated with the acquisition of the ability to produce crystallins. PMID- 3102306 TI - Glycoconjugates in the colons of New World monkeys with spontaneous colitis. Association between inflammation and neoplasia. AB - A spontaneously occurring experimental model of chronic colitis has been described in three closely related species of New World monkeys. One species, Saguinus oedipus oedipus, has the additional feature of developing adenocarcinoma of the colon in this setting. Pathological and lectin histochemistry studies were undertaken in 50 such colonic specimens to determine if pathological or histochemical features were associated with the concomitant development of cancer. Chronic inflammation was found in all of the colons examined, and 14% had features of acute inflammation, which was significantly associated with those animals that developed cancer. An oncofetal glycoconjugate structure has been defined in human colons by the ability to bind peanut lectin. A similar glycoconjugate, probably a mucin, was expressed in the colons of 65% of these animals. A marked degree of expression of the mucin was significantly associated with those animals that developed cancer. A highly significant association was found between the presence of acute inflammation and the expression of the mucin. These studies demonstrate similarities in glycoconjugate expression between the human colon and the New World monkey model of spontaneous colitis. A form of mucin is expressed in these animals that is highly associated with both the presence of acute inflammation and the development of cancer elsewhere in the colon. In addition, an association between acute inflammatory activity and neoplasia was found, suggesting a potential etiologic linkage between the two. PMID- 3102307 TI - Screening for colorectal cancer in a high-risk population. Results of a mathematical model. AB - A mathematical model was used to estimate the cost-effectiveness of colorectal cancer screening strategies for people who are at high risk because of a first degree relative with colorectal cancer. The model uses indirect evidence about such factors as cancer incidence, sensitivity and specificity of different tests, and treatment effectiveness. The analysis indicates that for screening people over 40 yr old an annual fecal occult blood test may reduce colorectal cancer mortality by about one-third, either colonoscopy or barium enema may reduce mortality by approximately 85%, a 3-5-yr frequency for endoscopies or barium enemas preserves 70%-90% of the effectiveness of an annual frequency, and beginning screening at age 50 reduces effectiveness by 5%-10%. Although both barium enemas and colonoscopies appear to be effective in reducing mortality, the lower cost of the barium enema makes it a more cost-effective strategy. All of these estimates depend on the baseline estimates of each of the factors incorporated in the model; the conclusions are most sensitive to assumptions about the natural history of adenomatous polyps, the bleeding of adenomas and presymptomatic cancers, and the sensitivity of the fecal occult blood test. Recommendations about colorectal cancer screening must also consider factors such as discomfort, inconvenience, and the availability of various technologies. PMID- 3102308 TI - Zollinger-Ellison syndrome. Cure by surgical resection of a jejunal gastrinoma containing growth hormone releasing factor. AB - Zollinger-Ellison syndrome developed in a 46-yr-old woman due to a gastrinoma originating in the proximal jejunum. Resection of the tumor and adjacent lymph nodes containing metastatic carcinoma resulted in prompt reversal of all clinical and biochemical abnormalities, and she remains well 42 mo after surgery. To our knowledge, this patient is one of the first well-documented cases of primary jejunal gastrinoma causing the Zollinger-Ellison syndrome. The tumor contained numerous cells positive for gastrin and smaller numbers positive for serotonin, somatostatin, or bovine pancreatic polypeptide, as diagnosed by immunohistochemistry. In addition, a small subset of tumor cells was positive for growth hormone releasing factor. Our case is the first to document the presence of this neuropeptide in an enteric gastrinoma. PMID- 3102309 TI - No demonstration of gallbladder motility disorder. PMID- 3102310 TI - [Preparations for parenteral nutrition as agents increasing resistance to hypoxia]. PMID- 3102311 TI - [Effect of prostaglandin E2 on the reactivity of mesenteric microcirculation in toxic hepatitis and parenteral nutrition]. PMID- 3102312 TI - [Immunologic characteristics of rhesus system antigen RhO (D) isolated from human erythrocytes]. PMID- 3102313 TI - Inhibition and activation of UDP-glucuronyltransferase in alloxanic-diabetic rats. AB - Short or long term alloxan diabetes produced activation of oestrone and morphine glucuronidation and inhibition of p-nitrophenol glucuronidation in rat liver microsomes. Insulin treatment restored decreased glucuronyltransferase (GT) activity for p-nitrophenol and it did not abolish diabetes activation on oestrone glucuronidation. Triton X-100 detergent activation reduced differences between normal, diabetic and insulin treated rats in the glucuronidation rates of the substrates assayed. 1,4-Benzodiazepines inhibited morphine GT activity and stimulated oestrone GT activity in normal, diabetic and insulin treated diabetic rats. Activation and inhibition of GT activities for oestrone and xenobiotics in diabetes mellitus appears to be related with membrane perturbations of liver microsomes. PMID- 3102315 TI - An experiment in long-stay care in hospital. PMID- 3102314 TI - Bupropion. Effects on cerebral monoamines in rat and on blood pressure in dog. AB - Intravenous injections of bupropion into the femoral vein of dogs did not change cardiovascular peripheric responses because it did not affect significantly either arterial pressure or heart rate. In acute experiments bupropion increased the levels of DA, NA and 5-HT in the brain of rats. There was a remarkable correlation between the levels of monoamines and the hypermotility. PMID- 3102316 TI - [Gas chromatographic method of determining carbon monoxide and dioxide]. PMID- 3102317 TI - [Sanitary microbiological verification of recreational loads on the water area of seashore beaches]. PMID- 3102318 TI - [Evaluation of the course and intensity of serologic incompatibility based on the complex examination of the amniotic fluid]. PMID- 3102319 TI - [Serologic Rh incompatibility in the presence or absence of antigenic incompatibility of the ABO system]. PMID- 3102320 TI - [Changes in the C3 component of the complement system in the amniotic fluid in normal pregnancy and pregnancy complicated by Rh serologic incompatibility]. PMID- 3102321 TI - Molecular radii of probes used in studies of intestinal permeability. PMID- 3102323 TI - Comparative trial of sodium cromoglycate enemas with prednisolone enemas in the treatment of ulcerative colitis. AB - A double blind multicentre study comparing sodium cromoglycate (600 mg/100 ml) by enema with prednisolone (20 mg/100 ml) by enema is reported. The study was conducted over a nine week period in the treatment of 70 patients with ulcerative colitis. Analysis of symptoms showed significant decreases in scores for patients in both groups, both at four and eight weeks; the only difference between the two groups was a significantly greater improvement in the reduction of rectal bleeding after four weeks in the prednisolone group. On sigmoidoscopy, both treatment groups showed a highly significant improvement after four and eight weeks with no significant differences being seen between the groups. Histology of the rectal biopsies showed a significant improvement in the inflammation of the mucosa for both treatment groups after four and eight weeks with no differences being observed between the groups. There were no significant changes in eosinophils from baseline and no difference between the groups at four and eight weeks. PMID- 3102324 TI - [Cost-benefit-risk analysis of estrogen treatment in the climacteric]. PMID- 3102325 TI - [The pathophysiologic and therapeutic significance of circulating anticoagulants in SLE]. PMID- 3102322 TI - Effect of chronic ethanol intake on lactase activity and active galactose absorption in rat small intestine. AB - The effects of feeding a nutritionally adequate liquid diet containing 5% ethanol to rats over a four week period on intestinal lactase activity and the kinetics of jejunal galactose absorption in vivo have been determined. Both lactase activity and the maximum capacity for active, saturable galactose absorption (Jmax) were increased significantly after chronic ethanol ingestion. In contrast, uptake of the sugar via the phlorhizin-insensitive (passive) route was unaffected by ethanol. Our results imply the presence of an increased maturity of the enterocyte population on the villus surface in response to ethanol. The relevance of this work to uptake studies in alcoholics is briefly discussed. PMID- 3102326 TI - Developing a hospital's volunteer program. AB - Today's competitive environment is placing increasing and often conflicting demands on hospital social service departments. In these difficult circumstances, the use of volunteers may help provide services that would not otherwise be available. This article outlines a systematic approach to developing volunteer programs that avoids common pitfalls and is both effective and cost conscious. PMID- 3102327 TI - Selective regeneration of Bacillus subtilis protoplasts transformed to kanamycin resistance. AB - An HTY medium osmotically stabilized with 0.5 M D-glucitol was used for regeneration of Bacillus subtilis protoplasts. The application of glucitol as osmotic stabilizer allows simultaneous selection of cells resistant to kanamycin to be made since this antibiotic is not inactivated by glucitol when added to the regeneration medium. PMID- 3102328 TI - Bacterial tests as indicators for the detoxification of the mycotoxin penicillic acid by ammonia treatment. AB - The detoxification of penicillic acid by reaction with ammonia was examined by means of a polymerase assay using two strains of Escherichia coli (pol A+ and pol A-1) and a recombination assay using two strains of Bacillus subtilis (rec+ and rec-). A 100-fold surplus of ammonia added to penicillic acid abolished the cytotoxic and genotoxic effects of penicillic acid towards the bacteria under the test conditions. The study presents the possibility of detoxifying mycotoxins in feeds by ammonia treatment and demonstrates the suitability of bacterial assays as indicators for mycotoxins. PMID- 3102329 TI - [Hemorheologic effects of nitroglycerin. A placebo-controlled double-blind study]. PMID- 3102330 TI - [Sequelae of craniocerebral injuries in a neurologic patient sample--an attempt at interpreting post-traumatic headache]. AB - The sequelae of a head injury that had occurred at least six months previously, were examined in 457 patients. Neurological deficiencies, psychoorganic disturbances and disability caused by the injury correlated positively with its severity. Posttraumatic epilepsies were diagnosed approximately equally often in patients with minor head injuries and in those with more severe ones. It is probable that epilepsies have been diagnosed too often in patients with minor head injuries. Headache occurs significantly more often in patients with minor head injuries. This cannot be explained by the selection of patients alone. A hypothesis explaining the development of posttraumatic headache is presented and discussed. PMID- 3102331 TI - [Regulation mechanism of fibrinolysis system on vascular wall]. PMID- 3102332 TI - Health care cost containment: what is too much? PMID- 3102333 TI - A look at catastrophic medical expenses and the poor. PMID- 3102334 TI - Health policy versus budget cutting: a conversation with Rep. Pete Stark. Interview by John K. Iglehart. PMID- 3102335 TI - Unintended results of Medicare's national prospective payment rates. PMID- 3102336 TI - Effect of gonadectomy and exogenous sex hormone administration on the concentrations of hepatic oestrogen receptors and hepatic atypical sex hormone binding protein (HASP) in the rat. AB - The concentrations of hepatic oestrogen receptors and atypical sex hormone binding protein are regulated by sex hormones in different manners. Ovariectomy of female rats leads to a significant increase in the concentration of hepatic oestrogen receptors, which can be reversed following administration of either androgens or oestrogens. No differences are observed between total binding site and unoccupied receptor concentrations. Intact male rats contain significantly lower total binding site concentrations and these are not affected by either testectomy or subsequent androgen administration. However, treatment of male castrates with oestradiol leads to the induction of typical female levels. It is not possible to determine the concentrations of unoccupied receptors in intact or gonadectomized males, or rats of either sex treated with androgens, due to masking by the moderate affinity, high capacity oestradiol binder (hepatic atypical sex hormone-binding protein, HASP). Oestradiol binding to this protein is not affected by testectomy nor subsequent androgen administration, but is reduced pressed following treatment with oestradiol. It is also induced in ovariectomized rats by androgens. Oestradiol binding to this protein can be prevented by inclusion of sodium thiocyanate in the assay buffer, thereby permitting unhindered measurement of the oestrogen receptor concentrations. PMID- 3102337 TI - Increased fructose-lysine of nail protein and blood glucose control in diabetic patients. AB - Furosine, which was formed by acid hydrolysis of fructose-lysine, was determined and used as an indicator of glycosylated protein. The diabetic patients had significantly higher fructose-lysine levels in finger nails than healthy subjects [10.8 +/- 4.6% (mean +/- S.D.) vs 4.2 +/- 1.1%]. The best correlation was found between the fructose-lysine value and the fasting blood glucose level determined 3 to 5 months before sampling nails in diabetics. These results suggest that the furosine derived from fructose-lysine in finger nails may become an indicator of blood glucose control during the past 3 to 5 months in diabetics. PMID- 3102338 TI - Interaction between gabaergic and opioid pathways in the regulation of gonadotropin secretion in males. AB - The effects of naloxone infusion given together with an infusion of LRH on gonadotropin secretion, were studied in 6 normal male volunteers before and after pretreatment with the GABA-transaminase inhibitor, valproic acid. In concordance with previous studies, naloxone infusion augmented the LRH-stimulated secretion of LH. Baseline serum LH concentrations were not significantly different after valproic acid pretreatment compared to control values. Similarly, valproic acid pretreatment failed to blunt the naloxone-augmented LRH-stimulated secretion of LH. Our data suggest that the previously reported animal studies on the central suppressive effect of GABA on endogenous LRH release is less prominent than the suppressive effect of opioidergic regulatory mechanisms in the human male. PMID- 3102339 TI - Effects of corticotropin releasing factor and growth hormone releasing factor on pituitary hormone secretion in patients with congenital thyrotropin deficiency. Abnormal response of growth hormone to corticotropin releasing factor. AB - Blood concentrations of anterior pituitary hormones, ACTH, GH, TSH, PRL, LH, and FSH were determined in corticotropin releasing factor (CRF) test (synthetic ovine CRF 1.0 microgram per kg body weight) and growth hormone releasing factor (GRF) test (synthetic human pancreatic GRF-44 100 micrograms) in 2 female sibling patients with congenital isolated TSH deficiency, in their mother, in 2 patients with congenital primary hypothyroidism and in 8 normal controls. The patients with isolated TSH deficiency showed normally increased plasma ACTH and serum GH after CRF and GRF, respectively, and also showed an abnormal GH response to CRF. The serum GH showed a rapid increase to maximum levels (12.9 ng/ml) within 30 to 60 min followed by decrease. The possibility of secretion of abnormal GH could be excluded by the fact that on serum dilution, GH value gave a linear plot passing through zero. In addition, serum PRL, LH and FSH levels after CRF administration in case 1 and PRL after GRF in case 2 were also slightly increased but these responses were marginal. The mother of the patients, patients with congenital primary hypothyroidism, and normal healthy controls showed normal responses of pituitary hormones throughout the experiment. Data from the present study and a previous report show that abnormal GH response to the hypothalamic hormones (CRF, TRH and LHRH) may be observed in patients with congenital isolated TSH deficiency. PMID- 3102340 TI - Long-term care financing: will it bury tax reform? PMID- 3102341 TI - States bend laws to lure long-term care insurers. PMID- 3102343 TI - Private sector spearheading LTC financing. PMID- 3102342 TI - Fed, as employer, moves on long-term care. PMID- 3102344 TI - ProPAC: create "temporary" DRGs. PMID- 3102345 TI - Diverticulosis of the vermiform appendix in patients with cystic fibrosis. AB - This paper presents a study of diverticulosis of the vermiform appendix in patients with cystic fibrosis. The records of two hospitals were reviewed. A total of 39 autopsy specimens and 18 surgical specimens were obtained. Diverticulosis of the appendix was found in 14 per cent (eight of 57) of all appendices. Two of these cases also showed diverticulitis. These results stand in contrast to the incidence of diverticulosis of the appendix in the general population, which has been measured at 1 to 2 per cent in various reviews. PMID- 3102346 TI - Ampicillin resistant gonorrhoea in Hong Kong. PMID- 3102347 TI - Single dose aztreonam in treating gonorrhoea. AB - Of 108 consecutive patients with urogenital gonorrhoea treated with a single 1 g intramuscular dose of aztreonam, 102 were suitable for evaluation. There was 100% cure at urogenital sites but treatment failed at three of 14 (21%) rectal or pharyngeal sites. In vitro resistance to aztreonam was not noted. PMID- 3102348 TI - Identification of penicillinase producing Neisseria gonorrhoeae in Chile during clinical and microbiological study of gonococcal susceptibility to antimicrobial agents. AB - The first penicillinase producing isolates of Neisseria gonorrhoeae (PPNG) identified in Chile were discovered during a clinical and microbiological study to compare the efficacy of penicillin (4.8 MIU aqueous procaine penicillin G plus 1 g oral probenecid) and tetracycline (1.5 g followed by 500 mg four times daily for four days) treatment regimens for acute uncomplicated gonorrhoea. Penicillin treatment was effective in 93.1% (282) of 303 patients, whereas tetracycline was effective in 98.3% (233) of 237 patients. Six of the penicillin treatment failures were attributable to PPNG strains. In all, 21 PPNG strains were identified during the study. They were genetically identical, having a wild type auxotype, a WII/III serotype (serovar Bajk), and carrying cryptic and transfer plasmids and an Asian type penicillinase producing plasmid. In addition, 674 non PPNG isolates were tested for their susceptibility to eight antimicrobials. Over 95% were sensitivie to 1 mg/l of penicillin, ampicillin, cefotaxime, cefuroxime, and erythromycin, over 90% were sensitive to 1 mg/l of tetracycline and 2 mg/l of thiamphenicol, and all were sensitive to spectinomycin. Of 226 non-PPNG isolates characterised for plasmid content and auxotype, 90% (205) were either wild type or proline requiring, 67% (153) carried only the cryptic plasmid, and a further 31% (71) carried both cryptic and transfer plasmids. Unusually, three of four isolates lacking the cryptic plasmid carried only the transfer plasmid. PMID- 3102349 TI - Penicillinase producing Neisseria gonorrhoeae in a hospital in Barcelona, Spain. PMID- 3102350 TI - Infection with penicillinase producing Neisseria gonorrhoeae in Catalonia. PMID- 3102351 TI - Enhancement of the B-cell response to Staphylococcus aureus Cowan strain 1 by natural human gamma interferon. AB - The effects of interferon (IFN) on the B-cell response to Staphylococcus aureus Cowan strain 1 (SAC) were studied comparatively with natural human IFN-alpha, IFN beta, and IFN-gamma, employing equal units of their anti-viral activity. First, the response was investigated in peripheral mononuclear cells obtained from healthy individuals, and next, confirmed in cultures employing B-cell enriched populations derived from tonsils obtained at tonsillectomy from patients with chronic tonsillitis. B cells were purified by rosetting out T cells with sheep red cells followed by the removal of adherent cells on a plastic surface. The results show that the SAC-stimulated lymphoproliferative response was enhanced in the presence of IFN-gamma in a dose-related manner, at concentrations ranging from 10 to 1000 IU/ml, both in peripheral mononuclear cells and tonsillar B-cell enriched fractions. In contrast, IFN-alpha and IFN-beta did not enhance or suppress SAC-stimulated blastogenesis in either lymphocyte preparation. The enhancing effects specific to IFN-gamma were more remarkable in cultures stimulated with a suboptimal dose (0.002%) of SAC than when the optimal dose (0.005%) was employed. PMID- 3102352 TI - Human T lymphocytes stimulated by phytohaemagglutinin undergo a single round of cell division without a requirement for interleukin-2 or accessory cells. AB - Monocyte-depleted human T lymphocytes completed a single round of DNA synthesis and cell division when treated with phytohaemagglutinin (PHA). Direct assay of culture supernatants showed that very low amounts of interleukin-2 (IL-2) were synthesized in these cultures. Furthermore, the first round of cell division was totally unaffected by the addition of saturating amounts of anti-Tac, a monoclonal antibody against the IL-2 receptor. These data strongly suggest that stimulation of IL-2 receptors by IL-2 was not required for the completion of the first round of mitosis. By contrast, proliferation of the daughter cells produced by the first cell doubling required the addition of exogenous IL-2 and was totally abolished by anti-Tac. These results were confirmed by experiments using single lymphocytes, which also showed that accessory cells were not required during the first cell doubling of PHA-stimulated lymphocytes. We therefore propose a modified model for in vitro T-lymphocyte activation, wherein PHA stimulate a single round of cell proliferation without a requirement for stimulation by IL-2. The resulting daughter cells now require IL-2 for further proliferation. By analogy, we suggest that triggering by antigen in vivo (in the context of products of the major histocompatibility locus) may also stimulate a single round of IL-2-independent division in appropriate clones of T lymphocytes, with the resulting population of daughter cells requiring IL-2 for further expansion of the population. PMID- 3102353 TI - Effects of Ly-5 antibodies on antibody-dependent cell-mediated cytotoxicity (ADCC). AB - Antibodies to a number of cell surface antigens expressed on mouse spleen cells were tested for their ability to inhibit antibody-dependent cell-mediated cytotoxicity (ADCC) of antibody-coated sheep erythrocytes (Ab-SE) in the absence of complement. Of the antibodies tested, only the antisera to Ly-5 and H-2 antigens significantly inhibited ADCC by spleen cells reactive with those antisera. Inhibition by Ly-5 antisera was shown to be allotype-specific by inhibition experiments using C57BL/6-Ly-5.1 (B6-Ly-5.1) and congenic C57BL/6-Ly 5.2 (B6-Ly-5.2) mice. Inhibition by Ly-5.1 antiserum appeared not to be due to competition for the Fc receptor (FcR), since in mixing experiments 'third-party' thymus cells treated with Ly-5 antiserum did not inhibit the cytotoxic activity of untreated cells. In comparing inhibition induced by antisera to H-2 and Ly-5 antigens, Ly-5.1 antiserum was more inhibitory at nearly every dilution tested. In addition, F(ab')2 fragments of Protein A-purified Ly-5.1 antibody were inhibitory to BALB/c spleen effector cells in ADCC of Ab-SE, whereas F(ab')2 fragments of H-2 antibodies had no effect. Because ADCC of tumour cells may share a common lytic mechanism with ADCC of erythrocytes, several antisera to cell surface antigens found on spleen cells were tested for inhibition of ADCC to antibody-coated P815 tumour cells (Ab-P815). As seen in ADCC to Ab-SE, anti-Ly 5.1 was a more potent inhibitor than antibody against either H-2k or H-2d antigens. The results are discussed in the light of the ability of Ly-5 antisera to inhibit various types of cell-mediated killing. PMID- 3102356 TI - Time course of antibody response to Theileria annulata. PMID- 3102355 TI - Suppression of human lymphocyte responses by Trypanosoma cruzi. AB - Virtually nothing is known about the basis for the immunosuppression associated with human T. cruzi infection. We have used an in vitro system to explore this effect. Incubation of human peripheral blood mononuclear cells (PBMC) with blood forms of T. cruzi abrogated their responses to suboptimal, optimal and supraoptimal doses of Con A, PHA or PWM, whether or not monocytes were depleted. Killed parasites were not suppressive. Maximal suppression (74%) occurred when the parasites were present during the entire culture period (96 hr), although significant suppression (33%) was seen when the organisms were added 24, 48 or 72 hr after initiation, suggesting that the early stages of lymphocyte activation had been impaired and that a second generation of cells was also affected. The 4 day supernatant medium of a T. cruzi suspension supported PBMC responses to Con A as well as medium incubated alone, indicating that suppression did not result from parasite removal of essential nutrients. Furthermore, 96 hr after mitogenic stimulation, the proportions of viable PBMC in cultures containing or lacking the parasites were comparable. Although T. cruzi binds Con A and PHA, this absorption was not the cause of reduced responsiveness since optimal concentrations of Con A and PHA remained in solution under our conditions. Levels of IL-2 in PHA stimulated PBMC cultures were markedly reduced in the presence of T. cruzi. However, exogenous IL-2 failed to restore lymphocyte responsiveness. T. cruzi neither absorbed nor inactivated IL-2. Thus, the noted suppression appeared to involve at least deficient production and utilization of IL-2. PMID- 3102354 TI - Production of lymphotoxin and tumour necrosis factor by a T-cell hybridoma. AB - It is known that two major cytotoxins, lymphotoxin (LT) and tumour necrosis factor (TNF), are produced by T cells and macrophages, respectively. We report in this paper that a human T-cell hybridoma, AC5-8, produces TNF in addition to LT depending on the kind of stimuli used. When phorbol myristate acetate (PMA) and concanavalin A (Con A) or PMA alone were used to induce AC5-8 cells to secrete a cytotoxin, we found that the cytotoxin secreted was antigenically indistinguishable from LT. On the other hand, when AC5-8 cells were activated by PMA and A23187, they secreted another cytotoxin which was antigenically indistinguishable from TNF, in addition to LT. These two cytotoxins could be separated by affinity chromatography on a column of Con A-Sepharose. A cytotoxin, which did not bind to the Con A-Sepharose column and showed about 70-95% of the total cytotoxic activity secreted from AC5-8 cells stimulated with PMA and A23187, was found to be antigenically identical to TNF. The other cytotoxin, which bound to the Con A-Sepharose column and showed only 5-30% of the total activity induced by PMA and A23187, was found to be antigenically identical to LT. PMID- 3102357 TI - A highly diverged beta 1 exon in the DR region of the human MHC: sequence and evolutionary implications. AB - The DR subregion of the human major histocompatibility complex from a DR4 haplotype includes the well-characterized DR alpha, DR4 beta, DR(MT3)beta psi genes. In addition, the region between the DR alpha and the proximal DR(MT3)beta contains several copies of conserved DR beta-related sequences. These repeated elements, numbered II, III, and IV, include the DR beta signal sequence and a region located further upstream. Further examination of these conserved sequences showed that DR beta first intron sequences are present at the 3' ends of these repeats. Progressively longer portions of the DR beta first intron are conserved from repeat II to repeat IV, producing a gradient of conservation. The most complete repeat element of repeats II, III, and IV is associated with a lone beta 1 exon (DR beta 1). Upon sequencing, DR beta 1 was found to contain several deleterious mutations, indicating that it is nonfunctional. DR beta 1 has accumulated a large number of replacement substitutions and mutations at positions which are invariant in beta 1 domains from expressed DR beta genes: 77.8% of the nucleotide substitutions were replacement substitutions, and 41.5% of the amino acids at invariant positions have been altered. Calculations based on these figures suggest that DR beta 1 may have become inactive approximately 25 million years ago. There are, however, two histidine residues within a variable region which are unique to DR beta 1 and the DR4 beta gene, suggesting that they represent a gene pair which probably evolved by duplication of a single DR beta chain gene. PMID- 3102358 TI - Comparison of rat MHC class I antigens by peptide mapping. AB - Monoclonal antibodies specific for the rat major histocompatibility complex (MHC) class I antigens RT1.An, RT1.Au, and RT1.Eu were used for immunoprecipitation of antigens biosynthetically radiolabeled with 14C- or 3H-labeled arginine, lysine, and tyrosine; with arginine or tyrosine alone; and with or without tunicamycin in the culture medium. Heavy chains of the glycosylated and unglycosylated antigens were purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and their tryptic and chymotryptic peptides were compared by high performance liquid chromatography. The antigens coded by the same locus in two different haplotypes (An and Au) differed by 30%, whereas the products of two different loci in the same haplotype (Au and Eu) differed only by 1-3%. Comparative analysis of the data for samples labeled with single amino acids indicated that two amino acids in Au have been substituted by an arginine and probably by a tyrosine residue, respectively, in Eu. The high degree of homology between the products of the A and E loci in the same haplotype accounts for the difficulty in detecting recombinational events within the MHC of the rat by classical serological approaches. PMID- 3102359 TI - Human lambda light chain locus: organization and DNA sequences of three genomic J regions. AB - Evidence for the genomic organization of human lambda light chain joining (J) region gene segments is presented. A mouse J lambda probe was used in Southern hybridizations to localize joining region sequences in a cosmid clone containing the genomic cluster of six human lambda constant (C) region gene segments. The results of these hybridizations suggest the presence of at least one J gene segment upstream from each constant region gene segment. The DNA sequences indicate that the human J lambda 1, J lambda 2, and J lambda 3 gene segments have consensus nonamer and heptamer sequences, proposed to be involved in V-J joining, are capable of encoding the known amino acid sequences for the respective J peptides, and have a sequence which could give a functional RNA splice site at the end of their coding regions. Our data show that a single functional J is located 1.3 or 1.6 kb upstream of each of the C lambda gene segments known to encode the Mcg, Kern- Oz-, and Kern- Oz+ isotypes. Therefore, the gene organization of this region of the human lambda locus is J1C1-J2C2-J3C3. The DNA sequences of J lambda 1, J lambda 2, and J lambda 3 presented in this paper establish that a single J lambda gene segment precedes each expressed C lambda gene segment, and support a model for the evolution of the human lambda JC clusters where J1C1 and J2C2-J3C3 arose from different ancestral JC units. PMID- 3102361 TI - Transferable drug resistance in Neisseria gonorrhoeae. PMID- 3102362 TI - Correlation of pyocyanine & pyocin production by clinical isolates of Pseudomonas aeruginosa. PMID- 3102360 TI - Analysis of the D-region products of H-2q using monoclonal antibodies reveals the expression of a new class I-like molecule. AB - To analyze how many D-region-encoded molecules could be detected in H-2q, we produced a panel of nine monoclonal antibodies from AKR (KkDk) anti-AKR.M (KkDq) immunizations. All of the Dq region antibodies cross-reacted on Dd and/or Ld, and all except one cross-reacted on Db, confirming the previously observed serologic and amino acid sequence homology between the D-region products of H-2d, H-2b, and H-2q. All of these monoclonal antibodies precipitated 46,000 dalton molecules from both cell-surface-labeled and biosynthetically labeled B10.AKM spleen cells, indicating that all were reactive with class I-like molecules. Sequential immunoprecipitation analysis with one of these antibodies, 66-3-5, reveals the presence of a previously unidentified class I-like molecule. Tryptic peptide map analysis reveals that this molecule may be the product of a newly described H-2Dq region gene. PMID- 3102363 TI - Effect of cigarette smoke inhalation on certain pulmonary & hepatic drug metabolizing enzymes in vitamin A deficient rats. PMID- 3102364 TI - In vitro antibacterial activity of Neem oil. PMID- 3102365 TI - Clinical performance with contraceptive vaginal rings containing levonorgestrel. PMID- 3102366 TI - Enteric fever due to double salmonella serotypes. PMID- 3102367 TI - Clinical and pathological features of Schistosoma mansoni infection in the Eastern Province of Saudi Arabia. PMID- 3102369 TI - Characterization of vascular relaxant factor released from cultured endothelial cells. AB - Cultured bovine endothelial cells were grown on microcarrier beads. Columns (0.2 ml) packed with microcarriers were perfused with oxygenated (20% O2) Tyrode's solution containing indomethacin (10 microM), and the effluent was passed through precontracted, endothelium-denuded detector arteries. When the endothelial cells were stimulated with bradykinin (3-100 nM), adenosine 5'-triphosphate (0.3-30 microM), or calcium ionophore A23187 (10-300 nM), they released dose-dependently a nonprostanoid compound that dilated the detector vessel. The factor, probably identical to the endothelium-derived relaxing factor of native endothelium, evoked dilations of the same magnitude in different types of detector vessels (rabbit thoracic aorta, rabbit femoral artery, canine coronary artery). However, this relaxant factor was significantly more effective in arteries precontracted by norepinephrine or serotonin than in arteries precontracted by potassium depolarization. Thus, its dilator action resembles that of the nitrovasodilators. The factor is labile, with an apparent half-life in the range of 20 to 30 seconds. Its dilator potency was inhibited by dithiothreitol (0.2 mM), metyrapone (0.2 mM), nordihydroguaiaretic acid (20 microM), and hemoglobin (1 microM), all of which apparently inactivated the factor. Synthesis or release (or both) of the relaxant factor was abolished by methylene blue (1 microM). High PO2 levels (greater than 400 mm Hg) in the perfusate markedly reduced the release of the relaxant factor from the cultured cells. This study demonstrates that a vascular relaxant factor is released from endothelial cells in monoculture by adenosine 5' triphosphate, bradykinin, and A23187 and establishes such a culture as a useful tool for analyzing the mechanisms of endothelium-dependent vasomotion. PMID- 3102368 TI - Diabetic ketoacidosis. PMID- 3102370 TI - [Amino acid administration in acute, compensated renal failure in the post traumatic phase]. AB - Three patient groups compensated acute renal failure and previous surgery were evaluated, who had been nourished isocaloric (1700 kcal) and practically isonitrogen (33-35 g amino acid), but of various mixtures of amino acids. Besides the uniform daily energy intake of 750 ml of 40% invert sugar and 250 ml of 20% Lipofundin, the daily amino acid infusion of group I (n = 13) was only 500 ml EAS pfrimmer (34.5 g), of group II (n = 10) 250 ml EAS pfrimmer and 250 ml of 7.5% Intrafusin, and of group III (n = 16) 250 ml EAS pfrimmer and 350 ml Aminofusin Hepar (33.1 g). During evaluation of the aminograms, low initial values under the bottom reference region of glycine, serine, arginine and histidine in serum were recorded at the start of the trial in all 3 patient groups. During the course of the 4-day infusion therapy, the serum values of patients in groups II and III appeared to improve more than those in group I. Contrarily, the serum levels of phenylalanine, methionine and 3-methyl histidine were 2-3 times higher than the reference region at the start of the trial. With regard to a decrease in the high serum levels, patient group II appeared to be superior to groups I and III. No significant differences were observed during the clinical course. PMID- 3102371 TI - Elimination of amino acids in chronic renal failure. AB - Elimination of parenterally administered amino acids was investigated in patients with chronic renal failure (CRF) (10 on conservative treatment = CT, 13 on regular hemodialysis therapy = HD). In a bolus injection protocol 0.1 g amino acids as a 10% solution containing essential and nonessential amino acids were infused and pharmacokinetic parameters of 17 amino acids were calculated. The mean elimination half life was increased by 40% in CT and 87% in HD (p less than 0.001 CT and HD versus controls). Total clearance was reduced in CT (p less than 0.001 versus HD and controls). In CT clearance of phenylalanine, proline, alanine, histidine and arginine was reduced, of none of the amino acids elevated. In HD clearance of methionine, lysine, aspartic acid and serine was increased, of proline decreased. The total transfer rate was reduced in CT (p less than 0.025 versus controls) and transfer of threonine, aspartic acid, glutamic acid, alanine, histidine and arginine was reduced in these patients. Mainly due to elevated basal plasma concentration transfer of methionine was elevated in CT and HD. In dialysis patients transfer of isoleucine, tryptophan, glycine and serine was increased. Despite variations of absolute values of clearance between the two groups investigated relative clearance rates of amino acids were similar because of a uniform increase of clearance of about 37% in HD compared to CT (p less than 0.001). Results indicate that the elimination of parenterally administered amino acids is grossly altered in uremia and that in patients on CT and HD a uniform elimination pattern can be observed. PMID- 3102372 TI - [Effect of L-carnitine on post-stress metabolism in surgical patients]. AB - The positive influence of L-carnitine administration on postaggression metabolism was investigated. Clinical examinations were executed on three groups of patients K1, K2, K3). Comparable surgical operations like stomach- and intestinal- resections were performed on these groups of patients. During the first three days after operation a nutritional diet (parenteral, standardized hypocaloric) with (K2: 2 g; K3: 4g) and without L-carnitine (K1) was given. The effects of L carnitine administration were evaluated by the following parameters: free fatty acids (FFS), triglycerides (TG), beta-hydroxybutyric acid (beta-OH-BS), acetacetate (ACAC), blood sugar (BZ), insulin (INS), lactate (LAK), pyruvate (PYR), total protein (GE), cholinesterase (CHE), urea production rate (PU), nitrogen of alpha-aminogroups (alpha-AN), nitrogen balance (NB), catabolic index (KI), BUN-Creatinine-quotient (B/K), total carnitine (GC), free carnitine (FC), acetyl carnitine (AC) and also the ratio between acetyl carnitine and free carnitine (AC/FC) in serum and urine. The results show no statistical significance. But they could lead to the following conclusions: Carnitine obviously reduces the insulin resistance. But it does not influence the post operative perturbation of glucose-utilization. Carnitine reinforces the utilization of long chain fatty acids and thus improves the energy conversion. Carnitine leads to an earlier positive nitrogen balance. By giving 4 g of carnitine a day, already after three days a repletion of tissue deposits is possible, and a dose dependence for carnitine administration exists for the utilization of long chain fatty acids and the repletion of tissue deposits. PMID- 3102373 TI - [The intravenous 15N metabolism test in assessing the effect of parenteral feeding on protein synthesis]. AB - It is possible to investigate the influence of parenteral applicated L-amino acids on protein metabolism of whole organism by the help of 15N-tracer technique in this paper described. We can determine the utilization of nitrogen parenteral applicated quantitatively. On the basis of graphical methods the protein synthesis rate can be calculated. We get this from mathematical models, based on 3-pool-model. The calculation bases on 15N-elimination in urine after intravenous infusion of 15N labeled amino acids solution during the time of 24 h (endproduct method). We describe 3 graphical methods, using the so-called values of plateau of cumulative 15N-excess amount (96 h) (plateau method A) or 15N abundance after 24 h (plateau method B) and the slope of the curve of 15N excess, amount at 24 h ('slope' method). By the help of these methods the therapeutical nutritive conceptions can be evaluated. PMID- 3102374 TI - [Biological availability of glutamine from N-acetyl-L-glutamine in intravenous administration. Studies in the rat]. AB - Glutamine may be important especially in the catabolic patient, due to its universal role in transamination reactions. Because of its instability, until presently, glutamine is not included in amino acid solutions for parenteral nutrition. The availability of glutamine from the stable derivate N-acetyl-L glutamine is investigated under the condition of a long-term parenteral nutrition by means of growth, N-balance, and amino acid concentrations in plasma, muscle and urine. For this purpose 2 groups of young healthy male rats (n = 6) are maintained entirely by parenteral nutrition for 12 days. Both groups are given 0.8 g N/kg/24 h as an amino acid solution without containing glutamine. Only one of the groups was supplied additionally with 0.4 g N as N-acetyl-L-glutamine. This resulted in a weight gain of 33 +/- 1.5 g and a cumulative N-balance of 1.5 +/- 0.045 g. In the group in which no acetyl-L-glutamine is given, weight gain is 27 +/- 1.8 g (p less than 0.05) and cumulative N-balance amounts only 1.16 +/- 0.034 g (p less than 0.001). In plasma and urine the amino acid concentrations are significantly elevated for the essential one in this group. The results indicate a good availability of glutamine from N-acetyl-L-glutamine when given intravenously to the rat. PMID- 3102375 TI - Ultrasound in the treatment of ankle sprains. AB - Ultrasound is commonly used in association with other forms of treatment in the management of sprains of the lateral ligament of the ankle. Despite its widespread use there is little scientific evidence to support its role in the management of sprained ankles. We have conducted a prospective, randomized, double-blind trial to compare the results of physiotherapy for sprains of the lateral ligament of the ankle without the use of ultrasound with physiotherapy which included ultrasound. The results in the 154 patients who entered the trial demonstrate that there was no significant difference between the results achieved by the group treated with ultrasound and by those managed without. PMID- 3102376 TI - Synovitis causes hypoxia and acidity in synovial fluid and subchondral bone. AB - The purpose of the present study was to evaluate the environmental changes in synovial fluid and subchondral bone during synovitis in rabbits in which the knee joint on one side was subjected to a procedure causing instability; a traumatic synovitis rapidly developed. Three weeks following the procedure, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2) and hydrogen ion concentration (pH) were measured in vivo in the juxta-articular bone and in the synovial fluid of both the normal and the affected sides. Mass spectrometry was used for simultaneous registration of PO2 and PCO2, while a monocrystalline antimony pH electrode was used for simultaneous measurement of pH in vivo. Hypoxia, hypercapnia and relative acidity were found in synovial fluid and subchondral bone of knees with synovitis. The metabolic environment of synovial fluid and subchondral bone was considerably changed at the 3-week stage of experimental osteoarthritis and this was probably secondary to regional venous congestion. PMID- 3102377 TI - Purification of Pseudomonas aeruginosa exoenzyme S. AB - Pseudomonas aeruginosa produces two distinct ADP-ribosyl transferases, exotoxin A and exoenzyme S, which differ in a number of properties including substrate specificity. Exoenzyme S was purified from culture supernatants of P. aeruginosa DG1. The procedure for purification consists of four major steps: ammonium sulfate precipitation, anion-exchange chromatography on DEAE-Sephacel, acetone precipitation in the presence of 1 M NaCl, and G-100 Superfine gel filtration chromatography. Exoenzyme S was monitored during purification by an assay for ADP ribosyl transferase activity, mouse toxicity, and sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified material exhibited ADP-ribosyl transferase activity, reacted with monoclonal antibodies to exoenzyme S, and was toxic to mice and a variety of tissue culture cell lines. PMID- 3102378 TI - Suppression of the delayed-type hypersensitivity and cell-mediated immune responses to Listeria monocytogenes induced by Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa-mediated suppression of the immune response to Listeria monocytogenes was investigated in mice. Because delayed-type hypersensitivity (DTH) footpad swelling to L. monocytogenes was suppressed equally in lipopolysaccharide-responsive and -hyporesponsive mouse strains, the lipopolysaccharide component of P. aeruginosa could not have been the suppressive agent. Mucoid P. aeruginosa cells were no more suppressive than their nonmucoid revertants; therefore, mucoid coating was not an additional immunosuppressive element. Interleukin-1 and macrophage inhibitory factor production to L. monocytogenes and clearance of L. monocytogenes from mouse spleens were all decreased by prior Pseudomonas infection, indicating that cell-mediated immunity, as well as DTH, was decreased to a sublethal Listeria dose. The timing of Pseudomonas exposure relative to Listeria sensitization was varied. P. aeruginosa injected 24 or 6 h before or at the same time as L. monocytogenes depressed DTH to Listeria challenge 7 days later. Animals treated in this way could not respond to reinfection with L. monocytogenes at 13 days. P. aeruginosa administered to L. monocytogenes-sensitized mice at the time of footpad challenge was suppressive, but these mice responded normally upon reinfection. It appears that P. aeruginosa induced two types of suppression to L. monocytogenes: a transient suppression, affecting DTH challenge but not resensitization, and a longer lasting suppression that did not permit mice exposed to P. aeruginosa at the time of Listeria sensitization to respond to subsequent Listeria exposure. PMID- 3102379 TI - An immunoreactive, water-soluble conidial wall fraction of Coccidioides immitis. AB - Arthroconidia stripped of their outer, hydrophobic wall layer release an immunoreactive, water-soluble fraction (SCWF), the composition of which is examined in this paper. The immunogenicity of SCWF was determined by its reactivity with anti-Coccidioides immitis complement-fixing antibody and tube precipitin antibody in a standardized immunodiffusion assay as well as reactivity in a lymphocyte proliferation assay. SCWF was shown to be more immunoreactive for immune lymphocytes than selected cytosol and culture supernatant fractions of C. immitis. Rabbit antisera raised against SCWF were used in immunoelectron microscopic and immunofluorescence studies to confirm that the immunoreactive components of SCWF are primarily associated with the inner conidial wall. The antigenic composition of the conidial wall fraction was characterized by advancing-line immunoelectrophoresis with the previously established coccidioidin reference system. Protein composition was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Chromatographic fractionation of SCWF was performed on a Sephacryl S-300 preparative column. Selected fractions which showed significantly higher immunoreactivity and less complex antigenic composition than whole SCWF were characterized. Two heat-sensitive antigens of Sephacryl fraction 3a were identified. One or both of these antigens may correspond to the complement-fixing antigen, which is potentially important as an immunodiagnostic antigen. Fraction 4 contained a previously described wall associated antigen (AgCS) which may also be of immunodiagnostic value. We conclude that the conidial envelope is a reservoir of immunoreactive macromolecules which may play significant roles in early stages of infection. PMID- 3102380 TI - M proteins of group G streptococci isolated from bacteremic human infections. AB - We studied seven strains of group G streptococci isolated from clinically severe bacteremic infections in six intravenous drug abusers. These group G strains multiplied luxuriantly in fresh human blood. On electron microscopy, they exhibited surface fibrillae similar to those observed in M-protein-rich group A streptococci, but they were not serologically M typable with a battery of 39 M antisera. Rabbit antisera raised against two of the group G strains (1618 and 1750) opsonized the homologous but not the heterologous isolates and exhibited type-specific Ouchterlony immunoprecipitin reactions. Moreover, antisera raised against peptic extracts of strain 1750 also promoted phagocytic killing of that strain. Anti-1750 reacted in high titer in an enzyme-linked immunosorbent assay against peptic extracts of the homologous strain; these antibodies were removed by absorption with 1750 cells but not by absorption with heterologous strains. These studies represent, to our knowledge, the first analysis of virulence factors of group G streptococci isolated from invasive human disease. The seven epidemiologically related blood isolates of group G streptococci possess distinct type-specific, antiphagocytic surface virulence factors analogous to the M proteins of group A streptococci. PMID- 3102383 TI - Meningococcal infections in the German Democratic Republic 1971-1984. AB - Since May 1979 all meningococcal strains isolated in the GDR have been investigated microbiologically. Despite a generally low incidence, a marked increase in meningococcal infections has been observed. From a total of 650 strains sent to our institute up to 1984, 515 could be serogrouped. 54 strains belonged to serogroup A, 292 to B, 125 to C, two to X, eight to Y, one to Z, 30 to W-135 and three to 29E. There were no substantial changes in the distribution of the groups. In our study we tried to find out whether there are any correlations between the epidemiological and microbiological data. A record was made of the age distribution, clinical picture and regional distribution of the meningococcal strains isolated. Rifampicin chemoprophylaxis of contacts was introduced in 1981. PMID- 3102381 TI - Activation of murine macrophages and a bovine monocyte cell line by bovine lymphokines to kill the intracellular pathogens Eimeria bovis and Toxoplasma gondii. AB - Macrophage (M phi)-activating lymphokines present in concanavalin A-stimulated bovine T-lymphocyte cultures (ConAS) were studied by assessing their effects on Eimeria bovis and Toxoplasma gondii growth in cultured bovine monocytes (BM) and mouse M phi. The in vitro development of both parasites was assessed by incorporation of [3H]uracil and by microscopic examination of parallel cultures. Incorporation of [3H]uracil into infected cultures was an accurate indicator of growth of both E. bovis and T. gondii in BM and mouse M phi. Sporozoites of E. bovis underwent merogony in untreated BM but not in mouse M phi, whereas T. gondii developed in both cell types. Inhibition of T. gondii growth was greatest in ConAS-treated BM, whereas preincubation of mouse M phi with ConAS resulted in about 80% growth inhibition. There was no significant difference between the inhibition of either T. gondii sporozoite- or tachyzoite-induced growth in ConAS treated cells, showing that activation pathways are equally effective against both stages. Treatment of ConAS with glycine-hydrochloride buffer (pH 2) resulted in a total loss of antiviral activity mediated by gamma interferon (IFN-gamma). When pH 2 dialyzed ConAS was used to activate BM, inhibition of T. gondii growth was only partially affected. Because bovine IFN-gamma does not activate mouse M phi and due to the partial effects of pH 2 on ConAS-induced growth inhibition, the major component(s) of ConAS responsible for T. gondii growth inhibition is distinct from IFN-gamma. Furthermore, IFN-gamma may act synergistically rather than being part of a priming sequence for M phi responsiveness to other lymphokines. Murine recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) was tested for any microbistatic activity against T. gondii sporozoites and tachyzoites. There was no significant difference in either colony formation or [3H]uracil incorporation between rGM-CSF-treated and control cultures, regardless of host cell type. Thus, rGM-CSF does not induce adequate M phi activation to kill T. gondii and is not a major microbistatic component of ConAS. rGM-CSF also had no effect on T. gondii infection in vivo. PMID- 3102384 TI - An unusual course for hepatitis A. PMID- 3102382 TI - Prospective study on humoral immune response induced by fungal infection in patients with hematologic malignancies. AB - To evaluate the immune response in an immunosuppressed population, antibodies against commercially available Candida albicans antigens were prospectively studied during 37 episodes of acute stomatitis caused by C. albicans and 36 episodes complicated by deep-seated mycoses in 62 adult patients with hematologic malignancies. During uncomplicated stomatitis in patients with acute leukemia, the mean peak IgM, IgG and IgA class enzyme-linked immunosorbent assay (ELISA) units differed significantly from the basic level preceding fungal infection. Mean time until peak values was 2.7-3.8 weeks after diagnosis of stomatitis. During systemic mycoses the antibody response was similar. Among patients with other hematologic malignancies, predominantly lymphomas, several were terminally ill and responded infrequently by antibody production. Similar results were given by Ouchterlony immunodiffusion and counterimmunoelectrophoresis. Thus, patients with acute leukemia showed an antibody response to fungal infection; the peak values, however, were somewhat delayed. PMID- 3102385 TI - In vitro activity of ofloxacin against 210 clinical isolates of typhoid salmonellae. AB - 210 clinical isolates of typhoid salmonellae, cultivated from blood of patients with typhoid fever (108 strains of Salmonella typhi, 99 strains of Salmonella paratyphi A and three strains of Salmonella paratyphi B) as well as 266 random clinical isolates of Escherichia coli (n = 152), Klebsiella spp. (n = 51) and Proteus spp. (n = 63) were tested for susceptibility to ofloxacin, using an agar dilution method. All the typhoid salmonellae were found to be highly sensitive to ofloxacin with MICs ranging from 0.03 mg/l to 0.12 mg/l. The sensitivity pattern of enterobacteriaceae was comparable to data published internationally. PMID- 3102386 TI - Investigations on ofloxacin: antibacterial activity and influence on the immune system. AB - The in vitro activity of ofloxacin was tested against freshly isolated strains, from clinical material, of Pseudomonas aeruginosa, Staphylococcus aureus, and coagulase-negative staphylococci, including strains that were resistant to methicillin and/or novobiocin. 97% of the Pseudomonas strains were inhibited by ofloxacin concentrations in the range of 0.78 to 6.25 mg/l, with 55% of the strains being inhibited by concentrations up to 1.56 mg/l. All of the staphylococci strains, including those resistant to novobiocin and/or methicillin, were sensitive to ofloxacin in the range 0.19 to 1.56 mg/l. The influence of ofloxacin on cellular and humoral host immunity was evaluated both in vivo and in vitro. The influence of the compound on phagocytic activity of human polymorphonuclear leucocytes was evaluated by luminol-enhanced chemiluminescence. Ofloxacin did not influence cell-mediated immunity. It had no effect on chemotaxis. The use of sub-inhibitory concentrations of ofloxacin enhanced the phagocytic kill rate. PMID- 3102387 TI - Ofloxacin, a new quinolone in the treatment of genitourinary and enteric infections. AB - During 1984 to 1986, 121 patients with gonorrhoea were treated with ofloxacin. This report is to summarize the results of our trial in patients treated with three different dose regimens of ofloxacin: A) a single 800 mg dose of ofloxacin (32 patients); B) a single 400 mg dose of ofloxacin (55 patients) or C) a twice a day dose of 600 mg ofloxacin (34 patients). In addition, 19 patients with urinary tract infection and eight patients with enteric fever were treated with 400 mg ofloxacin twice a day for seven to ten days. Out of 121 patients with gonococcal urethritis, only 107 patients were evaluable. Cure was obtained in 96.5%; 93.2% and 94.5% of the patients in groups A, B and C respectively. 16 out of 17 patients with urinary tract infection achieved clinical cure or improvement. The 16 patients were bacteriologically accessible; pathogens were eradicated in all of them. Ofloxacin was also effective in the treatment of enteric fever, in which eradication was achieved in all seven patients. 28% of Neisseria gonorrhoea and 29% of Salmonella spp. isolated in our community were beta-lactamase-positive. PMID- 3102388 TI - Interferon analogues from synthetic genes: an approach to protein structure activity studies. PMID- 3102389 TI - Peroxide and pteridine: a hypothesis on the regulation of macrophage antimicrobial activity by interferon gamma. PMID- 3102390 TI - Alloimmunization by plasma infusion. PMID- 3102391 TI - Thrombin stimulates arachidonate metabolism in murine tumor cells. AB - Thrombin can be formed in the tumor cell microenvironment following activation of the clotting cascade by procoagulants of cancer or host cells. We have tested here the effects of thrombin, either "endogenous" or "exogenous" (see below), on arachidonate mobilization from membrane phospholipids of mouse mammary tumor virus-induced (MMTV) carcinoma cells. These tumor cells exhibit in vitro a tissue type procoagulant activity (130 thromboplastin units/10(4) cells) and are therefore able to induce thrombin formation in a plasmatic milieu. To verify the effect of thrombin formation by tumor cell procoagulant ("endogenous thrombin"), either human or mouse platelet-free plasma (20% in DMEM) was added to the cell layer (prelabelled for 5 hr with a trace amount (0.013 microM) of 3H arachidonate) and the system was recalcified (15 mM CaCl2). Thin-layer radiochromatography of the culture medium showed a significant release of 3H labelled arachidonate products PGE2, PGF2 alpha and 6-ketoPGF1 alpha after 1 hr of incubation. To verify the effect of thrombin formation from host sources ("exogenous thrombin"), either bovine or purified human alpha-thrombin (0.1-10 U/ml) was added to the cells for different periods (from 5 min to 20 hr). Exogenous thrombin stimulated arachidonate release and metabolism in a dose related manner. With short labelling periods (0.013 microM 3H-arachidonate for 30 min-1 hr) thrombin stimulated the release of unmetabolized 3H-arachidonate, but not of 3H-arachidonate metabolites. These processes were inhibited by a specific inhibitor of thrombin enzymatic activity (alpha-NAPAP, 140 microM) and by a cyclo oxygenase inhibitor (ASA 4mM). Tumor-associated procoagulants may thus contribute not only to fibrin deposition but also to generation of multipotent mediators such as arachidonate metabolites. PMID- 3102392 TI - A line of non-tumorigenic mouse melanocytes, syngeneic with the B16 melanoma and requiring a tumour promoter for growth. AB - An immortal line of pigmented melanocytes, "melan-a", has been derived from normal epidermal melanoblasts from embryos of inbred C57BL mice. The conditions favouring proliferation of these cells largely resemble those for normal, non established mouse melanoblasts and melanocytes, and include a low extracellular pH and the presence of a tumour promoter, tetradecanoyl phorbol acetate (TPA) or teleocidin. Melan-a cells have the diploid chromosome number and do not form tumours in syngeneic or nude mice. They are therefore the first known line of non tumorigenic mouse melanocytes, although an aneuploid melanocyte line of untested tumorigenicity has been reported (Sato et al., 1985). Melan-a cells are syngeneic with the B16 melanoma and its sublines, and provide an excellent parallel non tumorigenic line for studies of the cellular and molecular basis of melanoma malignancy. PMID- 3102394 TI - Risk management: an epidemiologic approach. PMID- 3102393 TI - Chemical synthesis of alpha-inhibin-92 by the thiocarboxyl segment coupling method. AB - The amino acid residue peptide, alpha-inhibin-92 (alpha-IB-92), has been synthesized by the thiocarboxyl segment strategy. Three segments were synthesized by the solid phase method, purified, and characterized: [GlyS34]-alpha-IB-92-(1 34) (I), CF3CO-[GlyS65]-alpha-IB-92-(35-65) (II), and Msc-alpha-IB-92-(66-92) (III). All were reacted with citraconic anhydride followed by removal of the Msc group in III to give Ia, IIa, and IIIa, respectively. Peptide IIIa was coupled to IIa by the silver nitrate/N-hydroxysuccinimide procedure and, after removal of uncoupled segments and the trifluoroacetyl group, Ia was coupled followed again by removal of uncoupled segments. Final deblocking to remove citraconyl groups was accomplished under exceptionally mild conditions in aqueous acetic acid. The synthetic product was identical to natural alpha-IB-92 in amino acid analysis, HPLC, gel electrophoresis, and tryptic mapping. The synthetic peptide was indistinguishable from natural alpha-IB-92 in a radioimmunoassay and in an in vitro mouse pituitary assay for measuring suppression of FSH release in the presence of LHRH. PMID- 3102395 TI - Prospective microbiologic surveillance in control of nosocomial methicillin resistant Staphylococcus aureus. AB - A prospective microbiological surveillance (PMS) program was developed in a comprehensive hospital-wide effort for control of nosocomial methicillin resistant Staphylococcus aureus (MRSA). This PMS program entailed: active identification of colonized and infected patients; application of a screening microbiologic system for MRSA; isolation of colonized and infected patients; antibiotic decolonization of MRSA; and educational efforts. The PMS program was studied over three and one half years for its contribution to infection control of MRSA, early identification of nosocomial MRSA outbreaks, use of the highest yield surveillance culture sites, and cost effectiveness. Following initiation of the PMS program in December 1982, during an MRSA outbreak, the frequency of new MRSA cases declined from 14 to none by the end of a 3-month pilot study. The frequency of new MRSA cases stabilized at approximately 2 per month until October 1983, when the PMS system allowed prompt detection of a new outbreak of 11 cases. Following isolation and antibiotic decolonization, the frequency of cases again declined to 3 per month. A third outbreak in December 1985 again was promptly detected and controlled. Infection to colonization ratio decreased from a maximum of 1.5 during outbreaks to a minimum of 0.17 after outbreaks. Wounds and tracheostomy sites provided the greatest yield of detection of new cases of MRSA. During one 15-month period, 35 of the 43 new cases were detected initially at wounds and tracheostomy sites. No new MRSA cases were detected by a positive axillary or nares site alone. The estimated quarterly cost of outbreaks and infection paralleled the quarterly frequency of new MRSA cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102396 TI - Induced precipitation of calcium-oxalate crystals and its prevention in laboratory animals. AB - Induced precipitation of Ca-oxalate crystals and the possibility of its prevention were studied in dogs. In the first phase of the experiments precipitation of Ca-oxalate crystals in canine renal tubules was induced by intraperitoneal administration of Na-glyoxylate. Preventive medication (lipoic acid, vitamin B1, Milurit), applied in the second phase, resulted in a significant depression of induced precipitation. The successful experiments serve as a basis for clinical research aimed at a preventive medication of recurrent Ca oxalate stone formation. PMID- 3102398 TI - Fibrinolysis with intrathrombic injection of urokinase and tissue-type plasminogen activator. Results in a new model of subacute venous thrombosis. AB - The efficacy of intrathrombic deposition vs. parathrombic infusion of urokinase (UK) and tissue-type plasminogen activator (t-PA) was investigated in a canine model. Gianturco coils were placed by transcatheter techniques into the iliac veins of 12 dogs. Venography obtained 48 hours later showed formation of large thrombi. After heparinization, UK (24,000-48,000 IU/ml) or t-PA (12,500-25,000 IU/ml) was spray-injected at high pressure throughout test clots every half-hour using a steel catheter with multiple side holes. Between injections, the agent was infused below the clots. The contralateral thrombi received an equivalent dose of fibrinolytic agent by continuous infusion. In six cases, plasminogen was injected into test clots prior to activator treatment. Thrombi spray-injected with either activator lysed in 64 +/- 26 minutes. Four of six thrombi treated with parathrombic urokinase infusion showed partial lysis after 133 +/- 50 minutes. After parathrombic infusion of t-PA, three clots showed complete lysis, one showed partial lysis, and two demonstrated no lysis. There was no significant difference in lysis rate between intrathrombic UK and t-PA nor did prior intrathrombic injection of plasminogen accelerate lysis. In summary, intrathrombic injection of highly concentrated UK or t-PA lysed subacute thrombi more effectively than parathrombic infusion. PMID- 3102397 TI - A phase II study of alpha-difluoromethylornithine (DFMO) for the treatment of metastatic melanoma. AB - Difluoromethylornithine (DFMO) is an irreversible enzyme-activated inhibitor of ornithine decarboxylase, a key enzyme in polyamine synthesis. We have screened for potential anti-cancer activity of DFMO using a clonogenic assay, which suggested that melanoma might have sensitivity to this agent. Accordingly, we have performed a phase II trial of DFMO (2 g/m2 po q 8 h) in 24 patients, 21 of whom were evaluable for response. One patient achieved a complete response of a large subcutaneous mass for 11 months. Although stabilization is frequently difficult to measure, seven patients appeared to stabilize previously active disease, with a median duration of response of eight weeks. Toxicity was significant and DFMO was discontinued in five patients due to side effects - hearing loss alone in four and hearing loss associated with thrombocytopenia in the fifth patient. Hearing changes occurred in ten patients. Other side effects were mild. These data indicate that DFMO as a single agent may be an effective therapy for melanoma. A phase II trial of DFMO in previously untreated patients using a different schedule to decrease hearing loss is warranted. Additionally, several in vitro and animal models suggest that DFMO plus interferon are synergistic, and this combination might be used for a clinical trial as well. PMID- 3102399 TI - Measurement of three-dimensional anatomy and function of pulmonary arteries with high-speed x-ray computed tomography. AB - Pulmonary arterial geometry was quantitatively evaluated in five dogs. One was a control dog, two were subjected to monocrotaline administration, and two had a subclavian-to-pulmonary artery shunt. Measurements of pulmonary arterial anatomy were made with the dynamic spatial reconstructor (DSR), a high-temporal resolution, volumetric, roentgenographic, computed tomographic scanner. In the control dog, pulmonary arterial cross-sectional areas and segment lengths were measured both from images generated from DSR scans obtained during injection of contrast medium and from a methylmethacrylate cast of the same vascular tree. The correlations between the DSR and cast-based measurements of cross-sectional area and segment lengths were 0.98 and 0.97, respectively. Over periods of eight and 11 months' observation, the pulmonary arterial pressure in the two dogs with surgically created left-to-right shunts increased from 29/15 to 42/17 mm Hg and 19/12 to 25/16 mm Hg, respectively. The cross-sectional areas increased progressively in the proximal portion of the main lobar arteries, remained unchanged in the midportion, and decreased in the distal portion of these arteries. Similar changes occurred in one of the two dogs treated with monocrotaline injections, while in the other the taper of the distal vessels did not change significantly. Pulmonary vascular resistance, computed from cardiac output and pulmonary artery pressure, increased proportionately to the decrease of the cross-sectional areas of distal vessel in both the monocrotaline administration dogs; the resistance decreased proportionately to the increase of the pulmonary arterial cross-sectional areas in both of the surgical dogs. PMID- 3102400 TI - Demonstration of an indomethacin-sensitive mechanism regulating immune reactivity in Chagas' disease patients. AB - We investigated some aspects of the regulation of the immune response that were sensitive to the effect of indomethacin, an inhibitor of prostaglandin synthesis, in two groups of patients in the chronic phase of Chagas' disease, and in normal controls. One group of patients was defined as being infected but with no clinical evidence of cardiac involvement, while the other showed electrocardiographic alterations that are characteristic of Chagasic cardiomyopathy. The in vitro responses to mitogens (phytohemagglutinin and concanavalin A) and Trypanosoma cruzi antigens were evaluated in the presence or absence of indomethacin. It was found that the in vitro mitogenic stimulation by both phytohemagglutinin and concanavalin A of peripheral blood mononuclear cells from normal controls and infected and cardiomyopathic patients was significantly increased by indomethacin. An inverse correlation was found between the initial response to concanavalin A and the subsequent increase caused by the presence of indomethacin, for both the patients and the controls. Considering specific responses to T. cruzi antigens, we showed that in the presence of indomethacin these were significantly increased in infected patients, but not in cases of cardiomyopathy. Again, a significant inverse correlation was found between the basal responsiveness and the indomethacin-induced change. In general, infected patients showed changes in the presence of indomethacin that were most comparable to those of normal individuals. It would appear, therefore, that normal indomethacin-sensitive (prostaglandin-dependent) suppressor mechanisms operate in Chagas' patients. In certain cardiomyopathy patients, however, these control mechanisms may not operate; a possible consequence of this could be tissue damage. PMID- 3102401 TI - Antagonistic regulatory properties of the Fc region of immunoglobulin. AB - Coculture of human peripheral blood mononuclear cells with Fc fragments of human IgG, or the synthetic Fc region-derived peptide, p23, results in the release of oxidative products of arachidonic acid. Prostaglandin E was the major arachidonic acid metabolite found in the culture supernatants. Induction of polyclonal antibody production by Fc fragments and p23 is influenced by the concomitant production of prostaglandin E in culture. Addition of prostaglandin synthetase inhibitors, indomethacin and aspirin, to human peripheral blood mononuclear cell cultures resulted in a significant increase in the amount of polyclonal antibody produced. Moreover, addition of exogenous prostaglandin E to these cultures abrogated the ability of indomethacin to enhance Fc fragment-induced polyclonal antibody production. These results suggest that Fc fragments possess bifunctional immunoregulatory properties. PMID- 3102402 TI - Hospital and ambulatory services for selected illnesses. AB - National survey data were used to describe and analyze the treatment of selected illnesses: hypertension, heart condition, hernia, gynecological infection, menstrual disorder, other gynecological conditions, pneumonia, and urinary tract infection. The number of office visits, the rate of diagnostic testing, the average charge, and the use of inpatient and outpatient hospital services were analyzed in an econometric model of treatment. Differences in the treatment of patients with similar illnesses were associated with comprehensive insurance, the availability of hospital and physician resources, and other economic considerations. There was also evidence that hospital and ambulatory services were substituted for each other, as a result of economic as well as medical considerations. PMID- 3102403 TI - Families with catastrophic health care expenditures. AB - This article describes the characteristics of families with catastrophic health care expenditures. Based on data from a national sample, three overlapping groups of families are considered: those incurring annual out-of-pocket expenditures that exceed, respectively, 5, 10, and 20 percent of the family's income. Such families represent a small percentage of all families, but they account for a disproportionally large share of total health care expenditures. Nevertheless, the actual amounts spent out of pocket by most of these families are relatively small. Modest sums are financially burdensome to these families because they are more likely to be low-income and to be headed by someone who is not employed. Families with catastrophic expenditures are also more likely to be headed by someone 65 or older and, consistent with that, a greater share of their total expenditures is covered by Medicare. However, all other third-party payers cover a relatively smaller share of total expenditures for these families than they do for all families, reflecting the generally worse third-party coverage of families with catastrophic health expenditures. The implications of these findings for several current issues are discussed, including catastrophic coverage proposals for Medicare and proposed programs to help the medically indigent and the uninsured. PMID- 3102404 TI - Are larger dental practices more efficient? An analysis of dental services production. AB - Whether cost-efficiency in dental services production increases with firm size is investigated through application of an activity analysis production function methodology to data from a national survey of dental practices. Under this approach, service delivery in a dental practice is modeled as a linear programming problem that acknowledges distinct input-output relationships for each service. These service-specific relationships are then combined to yield projections of overall dental practice productivity, subject to technical and organizational constraints. The activity analysis reported here represents arguably the most detailed evaluation yet of the relationship between dental practice size and cost-efficiency, controlling for such confounding factors as fee and service-mix differences across firms. We conclude that cost-efficiency does increase with practice size, over the range from solo to four-dentist practices. Largely because of data limitations, we were unable to test satisfactorily for scale economies in practices with five or more dentists. Within their limits, our findings are generally consistent with results from the neoclassical production function literature. From the standpoint of consumer welfare, the critical question raised (but not resolved) here is whether these apparent production efficiencies of group practice are ultimately translated by the market into lower fees, shorter queues, or other nonprice benefits. PMID- 3102405 TI - Two-year follow-up of the PCA noncemented total hip replacement. AB - The early results with the PCA total hip replacement have been most gratifying, especially the absence of complications related to the acetabular component. The radiographic evaluation was done critically, and the finding of no progressive acetabular radiolucencies was unexpected. Longer-term evaluation of these interfaces is necessary, but the short-term results have been encouraging. No components have migrated despite the absence of adjunct fixation mechanisms such as screws and flanges. The pressfit achieved with the roughened hemispherical surface has been adequate, and the fixation with the two outrigger pegs appears to have been sufficiently stable to preserve the prosthetic stability and has resulted in successful anchorage of all the components. The results with femoral components are obviously related to technique. In a few early cases when undersized prostheses were used, loosening occurred, and four of these components advanced to detectable loosening. One of these components was revised since this analysis. Attention to detail with maximal filling of the proximal femur apparently led to improved results, with successful anchorage in all subsequent implantations. The application of the dimensional analysis before surgery may indicate those cases in which a tight fitting metaphysis cannot be achieved. In elderly patients who have osteoporotic bone, a substantial mismatch exists between the size of the metaphysis and the diaphysis, and it may be advisable to continue with cement in these cases. By applying the dimensional analysis to preoperative templating, the surgeon may be sufficiently informed to know that a tight fit can be achieved at surgery. No catastrophic failures have occurred. If loosening does occur because of undersizing of the prosthesis, the process appears to be gradual and, although associated with pain, does not result in sudden failure. Despite the prosthesis not being anchored by cement or collar, no sudden subsidence of the components has resulted. Patients' clinical performance has been somewhat slower when compared to cemented series. Performance seems to accelerate once weight bearing occurs, however, and after 2 years no difference exists between this series and a corresponding cemented series. Noncemented total hip arthroplasty appears to offer as good if not better results than cemented total hip arthroplasty, if performed correctly and in the appropriate patient. Successful outcome depends greatly on technique, but when technically adequate implantation has been performed, the results have been gratifying.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3102406 TI - The stimulus for bone formation. PMID- 3102407 TI - Prevention of heterotopic bone formation: clinical experience with diphosphonates. AB - Heterotopic bone formation after total hip arthroplasty is a common occurrence in patients with osteoarthritis, and severe amounts of ectopic bone may limit motion or cause pain. Diphosphonates have been suggested as a method of preventing ectopic bone formation, but no long-term clinical evaluation of their effectiveness has been published. Because patients with osteoarthritis appeared to respond well to diphosphonate therapy in an earlier study, we thought that they would be an appropriate group of patients to study. We evaluated the results of 177 patients with 200 total hip arthroplasties performed for primary osteoarthritis. Considerable postoperative heterotopic bone formation (classes III and IV according to the classification system of Brooker and associates) was found in 36 hips (18%). The incidence of heterotopic bone formation was found to be as high as in the patients who had received either a placebo or no drug therapy. The postoperative range of motion of the hips, as well as ratings for pain, walking, and function, did not differ significantly between the treated and untreated groups. Diphosphonates (EHDP) have been demonstrated to inhibit the growth of hydroxyapatite crystals in vitro by chemisorption onto the crystal surface and thus have been thought to have the potential of preventing pathological calcification in vivo. However, diphosphonates have no inhibitory effect on the formation of osteoid matrix, and the delay in mineralization of matrix is reversed when therapy is discontinued. Although this delay in mineralization was known at the onset of these clinical trials, we hoped that the ultimate amount of heterotopic bone would be less in the treated patients and that the range of motion would be improved as a result of delaying the process of mineralization. Unfortunately, the final range of motion in the diphosphonate treated patients did not differ significantly from that in the untreated group, and the final amount of heterotopic ossification was not reduced. Therefore diphosphonate therapy must be considered ineffective. PMID- 3102408 TI - Prevention of heterotopic bone formation in high-risk patients by postoperative irradiation. PMID- 3102409 TI - The Otto Aufranc Award paper. New advances in the prevention, diagnosis, and cost effectiveness of venous thromboembolic disease in patients with total hip replacement. PMID- 3102410 TI - Cytochemical localization of beta-galactosidase in resident and inflammatory peritoneal macrophages from C57BL mice. AB - A cytochemical method for the detection of beta-galactosidase (beta-Gase) in mouse peritoneal macrophages was used to study the ultrastructural localization of this enzyme in these cells. It was found that the reaction product for beta Gase was localized in the perinuclear cisternae, the endoplasmic reticulum, the Golgi complex, lysosomes, vesicles and on the cell surface of peritoneal macrophages from untreated C57BL mice. When examined by X-ray microanalysis the crystalline reaction product was found to contain bromine, an element present in the indolyl substrate which was used to identify beta-Gase. Injection of Proprionibacterium acnes (P. acnes) intraperitoneally or BCG intravenously caused a visible loss in beta-Gase from all the organelles and from the cell surface of the macrophages. PMID- 3102411 TI - Immunoelectron microscopic localization of carbonic anhydrase III in rat skeletal muscle. AB - The subcellular distribution of carbonic anhydrase III in rat soleus and vastus lateralis muscles was studied using an immunogold technique. The enzyme protein was found to be distributed diffusely in the cytoplasm of skeletal muscle cells. Red skeletal muscle (mainly type I fibers) revealed very strong immunogold staining whereas in white muscle (mainly type II fibers) gold particles were almost completely absent. No immunoreaction was observed in mitochondria or in other intracellular organelles. PMID- 3102412 TI - Lectin binding and surface glycoprotein pattern of human macrophage populations. AB - In the present study unstimulated and stimulated human blood monocytes, untreated and phorbol ester treated U-937 cells, as well as human peritoneal and alveolar macrophages were studied with respect to their surface membrane properties. Binding of different lectins and electrophoretic patterns of tritium labeled surface glycoproteins were compared. The analysis of surface glycoproteins could be interpreted as evidence for a common origin of the analysed cell populations. Furthermore, banding patterns of glycoproteins might be useful to define certain activation states within monocyte/macrophage differentiation. In contrast, lectin binding pattern did not clearly discriminate macrophage subpopulations. PMID- 3102413 TI - Distribution of synaptophysin immunoreactivity in guinea pig heart. AB - The distribution of synaptophysin, an integral polypeptide of presynaptic vesicle membranes, was investigated in guinea pig heart by immunohistochemistry using monoclonal antibodies. Synaptophysin immunoreactivity was found in varicose nerve terminals in all regions of the heart. Dense networks of immunoreactive varicosities were found to surround the vasculature and to be located within the subendocardial layers of the atria and ventricles, the highest levels being seen in the innervation of the conductive system. As synaptophysin is probably a component of the presynaptic vesicles of all synapses, its use as a marker of all nerve terminals within the heart is proposed. PMID- 3102414 TI - Fast neutron therapy for squamous cell carcinoma in the head and neck region: results of a randomized trial. AB - A randomized trial of fast neuron therapy compared with 4MV photons for patients with head and neck cancer is reported. One hundred and sixty-eight patients were recruited between 1977 and 1984. The minimum follow-up is 2 years. Three patients were withdrawn before treatment began. Eighty-five were allocated to neutron therapy and 80 to receive photon therapy. All patients had squamous cell cancers in one of four primary sites: oral cavity, oropharynx, larynx, and hypopharynx. Local tumor control was similar in both groups: 44.7% after neutrons and 45.0% after photons. Salvage surgery was performed on 18 patients in each treatment group for residual or recurrent cancer. Acute radiation reactions of the mucous membranes were significantly more severe after photons. The number of patients with serious late reactions was greater after neutron therapy but the difference was not statistically significant. There were six deaths related to late morbidity after neutron therapy but none after photon therapy. Survival was better after photon therapy but the difference compared with the neutron group failed to reach statistical significance. When intercurrent deaths are excluded, the difference is less marked. Photon therapy was clearly better in terms of disease-free survival giving a 2-year local disease-free rate of 41.3% (s.e. 5.5%) compared with 29.4% (s.e. 4.9%) after neutrons. PMID- 3102415 TI - The indications for total cutaneous electron beam radiation therapy of mycosis fungoides. AB - From 1977 to 1984, we treated 34 patients with mycosis fungoides and 9 patients with B cutaneous lymphomas. Eighteen patients with mycosis fungoides were treated with total skin electron irradiation (TSEI) and had a minimum follow-up of 15 months (range 15 months to 7 years). The lowest electron energy of the linear accelerator was 8 MeV therefore we placed a plexiglas screen between the patient and the machine; the resulting electron energy was 4 MeV. The total dose was 30 Gy delivered in 12 fractions over 40 days. There were 8 males and 10 females. The median age was 48 years (ranging from 13 to 78 years). All patients were staged as follows: Stage A = superficial lesions covering less than 50% of the body surface; Stage B = superficial lesions covering more than 50% of the body surface; Stage C = tumors involving the skin, lymph nodes and/or visceral organs. Five patients with Stage A (5/5) and 5 patients with Stage B (5/5) had a complete remission, 1 stage A patient relapsed 6 months after completion of treatment. All the Stage B patients recurred between 3 and 15 months. The recurrences were localized to the skin and were well controlled with topical nitrogen mustard or puvatherapy. Among the Stage C patients, 3 did not respond to treatment and died of their disease; the remaining 5 patients achieved complete remission but they all relapsed from 2 to 9 months following completion of treatment. The median follow-up was 32 months and the average time for relapse was 6.5 months. All relapses except one (15 months) occurred within the first year. We feel that total skin electron irradiation is indicated in Stage A and B patients. However, we feel Stage C patients should receive TSEI for palliative purposes only. PMID- 3102416 TI - Stereotactic percutaneous single dose irradiation of brain metastases with a linear accelerator. AB - The effectivity of stereotactic percutaneous single dose irradiations in the treatment of solitary brain metastases has been assessed in a series of 12 consecutive patients. Only radioresistant deeply localized metastases have been treated. Photon-irradiation was carried out with the convergent beam technique using stereotactic localization methods, in a linear accelerator facility. In 11 of the 12 patients no side effects occurred. The first 7 patients, who could be observed 3 months or longer, have been studied in detail. In each of these cases single dose irradiation with 20-30 Gy yielded arrest of tumor growth. In one case a marked decrease in contrast enhancement and in four cases shrinkage of the metastasis as well as a marked decrease of the edema occurred. In every patient a marked, sometimes dramatic improvement of the clinical condition was achieved, beginning a few days after irradiation. Stereotactic radiosurgery is a valuable tool in the treatment of inoperable, radioresistant brain metastases, the major advantage being high efficacy and smoothness of the procedure, as well as extremely short hospitalization times (2-3 days). PMID- 3102417 TI - Antiepileptic drugs in adolescents. AB - Adolescence is a critical developmental period in which major metabolic changes occur. The majority of adolescents with epilepsy can be fully controlled with medications and can lead productive lives. A knowledge of basic principles of pharmacotherapy with AEDs will enable the physician to treat effectively most adolescents with epilepsy. PMID- 3102418 TI - Pharmacological treatment of adolescent psychiatric disorders. AB - Psychopharmacological treatments of major psychiatric disorders during adolescence, including depression, anxiety disorders, schizophrenia, and attention-deficit disorder, are reviewed. Pharmacokinetic and psychological aspects specific to adolescence, which if ignored may impair or abolish drug efficacy, are examined. Recommendations are given for safe use of tricyclic antidepressants, monoamine oxidase inhibitors, and neuroleptics in this age group. Areas where future research is needed to make rational pharmacological choices are noted. PMID- 3102419 TI - Pharmacologic management of asthma. AB - Obstructive airway disease from asthma needs to be distinguished from other causes, classified with regard to clinical pattern, and assessed to identify severity and precipitating factors. Intervention of acute symptoms is most effective with inhaled sympathomimetic bronchodilators backed up with short courses of high-dose oral corticosteroids for symptoms that are suboptimally responsive to bronchodilation alone, especially for those patients with a history of emergency care requirements and/or hospitalization. Maintenance therapy with scheduled daily use of inhaled beta2 agonists, cromolyn, and slow-release theophylline can be used prophylactically for patients with chronic disease. The inhaled beta2 agonists are the most effective therapeutic agents for relieving acute bronchospasm and for decreasing responsiveness of the airways to specific stimuli such as exercise; however, even the newer agents have sufficiently short duration of effect to limit efficacy for maintenance therapy. Cromolyn and slow release theophylline are commonly used for chronic therapy; cromolyn has the merit of virtually no toxic potential but is less convenient and less likely to be effective, at least for more severe asthma, than theophylline. Corticosteroids uniquely decrease the inflammatory component of asthma, thereby decreasing or preventing airway obstruction from mucosal edema and secretions. Short courses of high-dose oral steroids without tapering provide useful and safe intervention for acute symptoms, whereas alternate-morning oral use and the new generation of topical inhaled agents provide acceptably safe alternatives for managing chronic disease not controlled with other measures. Nonpharmacological factors that require therapeutic consideration include environmental factors such as cigarette smoke and aeroallergens, and general physical conditioning. Compliance with the medical recommendations requires dealing with dysfunctional attitudes and beliefs held by the patient and/or family and the fostering of an internal locus of control by including the patient in the decision-making process. PMID- 3102421 TI - Cysteine-rich regions conserved in amino-terminal halves of raf gene family products and protein kinase C. AB - The predicted amino acid sequences of rat c-raf and A-raf products were subjected to homology search against other known amino acid sequences. We found that characteristic, cysteine-rich regions present in the amino-terminal halves of c raf and A-raf products had striking homologies with the cysteine-rich regions present in protein kinase C. These cysteine-rich regions had been shown to be deleted in the activated raf products and in the catalytically active protein kinase C produced by proteolysis. These facts suggest the significance of the cysteine-rich regions of raf products as well as those of protein kinase C in the regulation of kinase activities. PMID- 3102420 TI - Ophthalmic complications following megavoltage irradiation of the nasal and paranasal cavities in dogs. AB - Megavoltage x-radiation was used to treat orbital nasal, and paranasal cavity malignant neoplasia in 29 dogs. In each instance, the globe and adnexal tissues were within the treatment portals (entry and/or exit). Doses administered to tumors ranged from 3,680 to 5,000 cGy. Ocular reactions after irradiation were classified as mild in 5 of 29 cases (17.2%) and severe in 17 of 29 cases (58.6%). No ocular complications were noticed in 7 of 29 cases (24.1%). Complications frequently noticed included severe keratitis (41%), mild conjunctivitis (34%), severe conjunctivitis (28%), cataract (28%), and keratoconjunctivitis sicca (24%). Ocular complications that developed were not life threatening, but posed a threat to visual function and patient quality of life. Treatment for the complications included control of bacterial infection, reduction of tissue inflammation, and ocular surface protection when tear film deficiencies were noticed. Mild complications represented acute effects of irradiation, and typically resolved. Severe complications developed both acutely and as late irradiation effects. Those attributed to late irradiation effects were more vision threatening and altered the quality of life more than did the early effects. PMID- 3102423 TI - fos oncogene transfer to a transformed rat fibroblast cell line enhances spontaneous lung metastasis in rat. AB - When investigating the relationship of different oncogenes to metastasis, we found that transfer of the v-fos oncogene into a transformed rat cell line augmented spontaneous lung metastasis. The metastatic potential of the cell lines examined depended on the manner of integration and the extent of transcription of the fos genes. Thus, the fos oncogene is probably involved in certain events related to acquisition of metastatic potential. PMID- 3102422 TI - DNA amplification of the c-myc and c-erbB-1 genes in a human stomach cancer. AB - High-molecular-weight DNAs from 43 human primary tumor tissues were examined by Southern blot hybridization for possible rearrangement and/or amplification of the following protooncogenes: the c-myc, c-erbB-1, N-myc, c-mos and c-fos genes. In an adenosquamous cell carcinoma of the stomach, the c-myc and c-erbB-1 genes were found to be simultaneously amplified 5- and 30-fold, respectively. Cooperative expression of the amplified c-myc and c-erbB-1 genes might be involved in the genesis or progression of the gastric cancer. PMID- 3102424 TI - Urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)-nitrosamine in an analbuminemic congenic strain of rats with an ACI genetic background. AB - An analbuminemic congenic strain of rats originating from ACI (ACI-alb) rats was established. The rats were found to be highly susceptible to induction of urinary bladder cancer by N-butyl-N-(4-hydroxy-butyl)nitrosamine. Bladder cancers were observed in all male ACI-alb and normal ACI rats treated with the compound, but the average weight of the bladder including tumors was more in ACI-alb rats than in ACI rats (0.63 +/- 0.24 g and 0.18 +/- 0.05 g, respectively; ratio, 3.5:1). PMID- 3102425 TI - A novel agglutination test for the human immunodeficiency virus antibody: a comparative study with enzyme-linked immunosorbent assay and immunofluorescence. AB - A new serological test, the gelatin particle agglutination (PA) test, was developed for the detection of antibody to human immunodeficiency virus (HIV). The sensitivity of the PA test was the same as that of enzyme-linked immunosorbent assay (ELISA) among 761 US and Japanese sera tested. However, false positive cases were found in 1.2% of all sera in ELISA but in 0% in the PA test (P less than 0.05). There was 100% agreement of seropositivity between PA and a confirmatory indirect immunofluorescence (IF) test. In addition, the agglutination test was reproducible. Thus, the test should be useful for the mass screening of anti-HIV antibody in blood donors. PMID- 3102427 TI - The effect of age on susceptibility of rats to carcinogenesis by two nitrosamines. AB - The carcinogenic effects of identical doses of two carcinogenic nitrosamines each given to young (8-week-old) and old (54- or 65-week-old) F344 rats were compared. The two compounds were nitrosomorpholine, which was given in drinking water to females, and nitrosobis(2-oxopropyl)amine (BOP), which was given to males by gavage in oil. In both old (54 weeks) and young rats nitrosomorpholine at 100 mg/liter induced hepatocellular neoplasms in the liver of almost all rats, but the rate at which the neoplasms killed the animals was much slower in the old than in the young rats, and by this measure of potency the old rats given 100 mg/liter resembled young rats given 40 mg/liter. BOP administered at two dose rates, 2.5 mg twice a week for 35 weeks, and 6 mg twice a week for 29 weeks, induced neoplasms of the lung and of follicular cells in the thyroid and transitional cell neoplasms of the bladder and kidney pelvis in almost all animals when treatment began at 8 weeks, but many fewer, or none, of these neoplasms in male rats whose treatment began at 65 weeks. Instead, the old male rats developed hepatocellular neoplasms in the liver, none of which were seen in the young rats treated with BOP. There was no significant difference in mortality rate between young and old rats which would account for these differences in BOP treated rats. PMID- 3102426 TI - Modifying effects of butylated hydroxyanisole, di(2-ethylhexyl)phthalate or indomethacin on mouse hepatocarcinogenesis initiated by N-nitrosodiethylamine. AB - Preneoplastic and neoplastic liver and lung lesions were studied in male B6C3F1 mice given a single injection (80 mg/kg) of N-nitrosodiethylamine (DEN) intraperitoneally at 4 weeks of age, followed 1 week later by oral exposure to di(2-ethylhexyl)-phthalate (DEHP; at 6000 ppm in the diet), butylated hydroxyanisole (BHA; 7500 ppm in the diet) or indomethacin (10 ppm in the drinking water) alone or in combination (DEHP and BHA or DEHP and indomethacin), and continued for 29 weeks. DEHP or BHA alone and the combination of DEHP and BHA increased the incidence of DEN-initiated focal hepatocellular proliferative lesions (FHPL), including both microscopic hyperplastic foci and hepatocellular adenomas. Mice that received BHA alone or DEHP plus BHA had FHPL that were composed predominantly of eosinophilic hepatocytes, while FHPL in DEHP-exposed mice were basophilic. Indomethacin showed neither promotional or antipromotional effects, except for lung tumors. Mice receiving DEHP and indomethacin after DEN had significantly fewer lung lesions. A high incidence of renal papillary necrosis and nephropathy was observed in the indomethacin-DEHP exposed mice, while these lesions were not found in mice treated with indomethacin alone or DEHP alone. These findings suggest that BHA, an antioxidant, promoted pre neoplastic liver lesions while indomethacin, a known inhibitor of prostaglandin synthesis and a chemopreventive agent for colon and mammary tumors in other studies, had no effect on liver tumor promotion by DEHP. PMID- 3102428 TI - Effect of colony-stimulating factor-producing tumor on hemopoiesis in splenectomized mice. AB - The colony-stimulating factor-producing BMA-1 tumor was transplanted into splenectomized mice. These mice showed as much granulocytosis as non splenectomized mice bearing the tumor. The increase in the number of peripheral leukocytes induced per tumor weight was similar in the two groups. The hemopoietic cell population in the central bone marrow (tibia) was not increased by splenectomy. The total numbers of spleen colony-forming cells and granulocyte macrophage colony-forming cells in the whole body of tumor-bearing splenectomized mice were 29% and 58% of those in the tumor-bearing non-splenectomized mice, respectively. The expansion of hemopoiesis to the peripheral bone marrow in tumor bearing splenectomized mice was confirmed by histological examination of the tail bone. These results suggest that the lack of increase in the bone marrow cellularity is due to the space limitation, and that this is well compensated for by a great expansion of hemopoietic marrow to the peripheral bones in splenectomized mice. PMID- 3102429 TI - Effect of vitamin E on toxicity and antitumor activity of adriamycin in mice. AB - The use of vitamin E as a protective agent against adriamycin-induced toxicity in CDF1 and BDF1 mice resulted in potentiation of the chemotherapeutic index of adriamycin. A single dose of 15 mg of adriamycin per kg body weight produced a significantly reduced mean survival time. A dosage of adriamycin of 15 mg per kg body weight was employed in the following experiments. In P388 ascites tumor bearing mice, four consecutive injections of several doses of vitamin E before injection of adriamycin produced a significant prolongation of the mean survival. In concomitant studies of serum tocopherol content, 7 to 10 micrograms/ml appeared to be an appropriate serum concentration, in accordance with the result of our previous report on its immunopotentiation effect. alpha-tocopherol seemed to have a two- to three-fold greater physiological activity than alpha-tocopheryl acetate. Dietary vitamin E treatments offered no protection against adriamycin toxicity, because the serum tocopherol content reached only 4.39 micrograms/ml in mice given the vitamin E-sufficient feed in this study. The results suggested that an increase of the serum tocopherol level to about two to three times the untreated control would be required before the adriamycin treatment to reduce its toxicity. PMID- 3102430 TI - Antitumor activity of protein-bound polysaccharide from Cordyceps ophioglossoides in mice. AB - The effects of protein-bound polysaccharide (SN-C) extracted from Cordyceps ophioglossoides on the growth of transplanted allogeneic and syngeneic murine tumors were studied. SN-C given by intraperitoneal administration suppressed the growth of sarcoma-180 transplanted subcutaneously in mice. Intraperitoneal administration of SN-C also caused a significant prolongation of the life span of ICR mice inoculated intraperitoneally with Ehrlich carcinoma, and C3H/He mice inoculated intraperitoneally with a syngeneic tumor (X-5563). SN-C showed a significant cytocidal effect on cultured tumor cells. SN-C did not affect delayed type hypersensitivity (DTH) in normal mice, but restored the depressed capacity to raise DTH in tumor-bearing mice. These results suggested that SN-C may exert both direct and host-mediated antitumor effects. PMID- 3102431 TI - Characterization of polyethylene glycol-modified L-asparaginase from Escherichia coli and its application to therapy of leukemia. AB - For the purpose of clinical application to the therapy of human leukemia and lymphosarcoma, L-asparaginase from Escherichia coli was modified with 2,4-bis(O methoxypolyethylene glycol)-6-chloro-s-triazine (activated PEG2) by an improved method, which involves a purification step of activated PEG2 by gel filtration. The PEG2-modified asparaginase retained approximately 30% (73 IU/mg of protein) of the enzymic activity of the native enzyme, while it had almost wholly lost the immunoreactivity towards anti-asparaginase antibodies. The modified enzyme retained the characteristics of the native enzyme in terms of the pH- and temperature-dependencies of activity and stability, and the Km value for L asparagine. Administration of the modified enzyme to a dog with spontaneous lymphosarcoma induced complete remission without any toxic side effects. Seven children with multiple relapses of acute leukemia were treated with a regimen of cycles of methotrexate and native asparaginase. Three of these children developed anaphylactic shock. In contrast to the native enzyme, the successive administration of PEG2-modified asparaginase to those three patients was therapeutically effective without causing any allergic reaction. PMID- 3102432 TI - Decreasing trend of stomach cancer in Japan. AB - Stomach cancer is still the most common cancer in both males and females in Japan and the Japanese still show the highest mortality and incidence of stomach cancer in the world. However, the age-adjusted death rate of stomach cancer has shown a marked declining trend in both sexes for the last 25 years in Japan. Advocates of mass screening for stomach cancer and clinicians who specialize in the surgical treatment of stomach cancer may wish to claim credit for the decrease of stomach cancer mortality in Japan whereas advocates of primary prevention of cancer may wish to claim that the decrease of stomach cancer mortality is largely due to a decrease of stomach cancer incidence reflecting a recent change of dietary habits, especially the spread of western-style foods and diminished intake of traditional Japanese foods. In fact, the incidence rate of stomach cancer as estimated from the Osaka Cancer Registry shows a similar decreasing trend to the mortality. In many western countries, notably in the United States, the stomach cancer death rate has been decreasing for a long time, and is still decreasing. In those countries stomach cancer is now ranked as one of the rare cancers. It is hoped that the stomach cancer mortality and incidence will further decrease in the future in Japan in a similar way. Meanwhile, it is necessary to evaluate accurately the effectiveness of stomach cancer screening programs. It is also necessary and useful to explore the reasons for the recent decrease of stomach cancer incidence in Japan, which could be regarded as a "natural experiment" or "passive primary prevention." If we could identify the main reasons for the decrease of stomach cancer incidence from epidemiologic studies, it might be possible to speed-up the decrease of stomach cancer incidence in Japan, as well as in other countries which still show a relatively high incidence of stomach cancer. PMID- 3102433 TI - Human c-erbB-2 remains on chromosome 17 in band q21 in the 15;17 translocation associated with acute promyelocytic leukemia. AB - Using the human c-erbB-2 cDNA as a probe, we applied in situ hybridization techniques to acute promyelocytic leukemia cells with a 15;17 chromosome translocation, t(15;17)(q;22;q21), and were able to localize the c-erbB-2 gene on chromosome 17 to band q12 or q21 and on the proximal side of the breakpoint in the translocation. From this finding and previous observations by others, we presume that the gene and the breakpoint are both in band q21.1 of chromosome 17. We suggest possible involvement of the c-erbB-2 gene in the development of the t(15;17)-associated acute promyelocytic leukemia. PMID- 3102434 TI - Amino-acid substitution at codon 13 of the N-ras oncogene in rectal cancer in a Japanese patient. AB - The activation of proto-oncogenes in colorectal cancers in Japanese patients was studied using a mouse NIH3T3 cell transfection assay system. Of thirty-five colorectal cancers examined, one rectal cancer showed an unusually high transformation efficiency and, in this rectal cancer, the N-ras oncogene was found to be activated. Nucleotide sequence analysis of the activated N-ras showed a single G----C point mutation at the first letter of codon 13, resulting in the coding of arginine instead of glycine. This amino-acid substitution at codon 13 may be responsible for the efficient induction of transformants of NIH3T3 cells in vitro. PMID- 3102435 TI - Induction of gastric tumor and intestinal metaplasia in rats exposed to localized X-irradiation of the gastric region. AB - The induction of gastric tumor and intestinal metaplasia was examined in 8-week old male JCL/SD rats exposed to localized X-irradiation of the gastric region. The animals were each given two 20 Gy fractions of X-rays, with a one-week interval between fractions (total, 40 Gy). Nine atypical hyperplasias (20%) and 13 adenocarcinomas (28%) in the pyloric mucosa of the glandular stomach were found in 46 animals with X-irradiation. The incidence of intestinal metaplasia was 93% in the pyloric mucosa, 50% in the fundic mucosa and 96% in both the pyloric and fundic mucosa. Type B metaplasia (intestinal metaplasia without Paneth cells) was most common and type C (intestinal metaplasia with Paneth cells) was less frequent. No gastric tumor or intestinal metaplasia appeared in non-irradiated control rats. This study shows that local X-irradiation of the gastric region induced both gastric tumor and intestinal metaplasia independently. PMID- 3102436 TI - Potential tumor-promoting activity of bile acids in rat glandular stomach. AB - The potential tumor-promoting and -initiating activities of bile acids in the glandular stomach mucosa of F344 rats after administration by gastric intubation were studied. Taurocholic acid sodium salt at doses of 300 to 1200 mg/kg body weight and glycocholic acid sodium salt at doses of 400 to 1200 mg/kg body weight induced up to 100-fold increases in ornithine decarboxylase activity with maxima after 4 hr and up to 10-fold increases in replicative DNA synthesis with maxima after 16-17 hr in the pyloric mucosa of the stomach. Taurodeoxycholic acid sodium salt, taurochenodeoxycholic acid sodium salt and glycocholic acid also induced high ornithine decarboxylase activity, and glycodeoxycholic acid sodium salt and glycochenodeoxycholic acid sodium salt caused slight induction of ornithine decarboxylase activity, but taurolithocholic acid sodium salt did not induce ornithine decarboxylase activity at all in the pyloric mucosa of the stomach. Glycocholic acid sodium salt did not induce unscheduled DNA synthesis in the pyloric mucosa of the stomach. The present results suggest that six bile acids, but not taurolithocholic acid sodium salt, have potential tumor-promoting activities in the pyloric mucosa of rat stomach and that glycocholic acid sodium salt has no potential tumor-initiating activity in the pyloric mucosa of rat stomach. PMID- 3102437 TI - Possible single dosage effects of the nude gene: suppression of spontaneous development of thymoma and nephropathy in BUF/Mna-rnu/+ rats. AB - Single dosage effects of the rat nude gene (rnu) on spontaneous development of epithelial thymoma, muscle atrophy and nephrotic syndrome were studied by comparing littermates of rnu /+ and +/+ rats on a high thymoma strain, BUF/Mna, background. Heterozygous rnu/+ rats had a significantly smaller thymus than the +/+ littermates at 6 weeks of age. The incidence of thymoma at 12 months of age was extremely low in the female rnu/+ rats (3%) as compared with that of the +/+ rats (94%). Development of the nephrotic syndrome but not of the muscle atrophy was also suppressed in the heterozygotes. The results suggest that a recessive mutant gene, rnu, in a single dosage, interfered with critical steps of the disease processes of the thymoma and nephrotic syndrome in BUF/Mna-background rats. PMID- 3102439 TI - Establishment and characterization of a human pancreatic cancer cell line (SUIT 2) producing carcinoembryonic antigen and carbohydrate antigen 19-9. AB - A new tumor cell line (SUIT-2) derived from a metastatic liver tumor of human pancreatic carcinoma has been established in tissue culture and in nude mice, and maintained for over five years. In tissue culture, the cells grew in a monolayered sheet with a population doubling time of about 38.2 hr, and floated or piled up to form small buds above the monolayered surface in relatively confluent cultures. Chromosome counts ranged from 34 to 176 with a modal number of 45. Subcutaneous injection of cultured cells into nude mice resulted in tumor formation, histopathologically closely resembling the original neoplasm which had been classified as moderately differentiated tubular adenocarcinoma. Electron microscopic observation of the neoplastic cells revealed a characteristic pancreatic ductal epithelium. SUIT-2 cell line produces and releases at least two tumor markers, carcinoembryonic antigen and carbohydrate antigen 19-9, propagates even in serum-free medium, and metastasizes to the regional lymph nodes in nude mice xenografts. PMID- 3102438 TI - Inter-individual variations of arylhydrocarbon-hydroxylase activity in cultured human epidermal and dermal cells. AB - Arylhydrocarbon hydroxylase (AHH) activity was determined in cultured human epidermal and dermal cells with and without induction by benz[a]anthracene (BA). Large inter-individual variations were found in the basal and induced AHH activities and the induction ratio. The average basal AHH activity of 29 epidermal cultures in primary culture was 3.9 units (SD, 4.2; range, 0-16.3) (one unit was defined as 1 pmol of 3-hydroxybenzo[a]pyrene formed/mg protein/hr). AHH activity was induced time- and dose-dependently by BA. The average AHH activity induced by treatment with 13 microM BA for 24 hr was 97.4 units (SD, 69.4; range, 2.7-216.9). The induction ratio ranged from 0.6 to 262.0, but in the majority of cultures (15 of 27 cultures, 55%) it was less than 30. The mean induction ratio and SD was 51.1 +/- 63.0. The frequency distributions of basal AHH activity and the induction ratio were asymmetrical with a right tail. No correlation was found between the AHH activity or induction ratio and the age or sex of the donors or their residential district. The basal and induced AHH activities of dermal fibroblasts were both lower than those of epidermal cells; the average basal AHH level of 14 cultures was 1.5 units (SD, 1.4; range, 0-5.2), while the average induced AHH activity was 9.6 units (SD, 6.3; range 0-23.5). The induction ratio of dermal fibroblasts was lower than that of epidermal cells, the mean and SD being 7.5 +/- 7.4 (range, 1.9-27.0). There was no correlation between the AHH activities or induction ratios in epidermal and dermal cells isolated from the same donors. PMID- 3102440 TI - Effects of step-up and step-down heating combined with radiation on murine tumor and normal tissues. AB - Radiosensitizing effects of step-up heating (SUH) and step-down heating (SDH) on the tumor and skin were studied by using mammary adenocarcinoma transplanted to the foot of the C3H/He mouse. The tumor and skin responses were assessed by the tumor growth delay method and the skin reaction scoring method, respectively. Neither SDH (44 degrees, 10 min----42 degrees, 30 min) nor SUH (42 degrees, 30 min----44 degrees, 10 min) alone caused a substantial tumor or skin response. When the heat treatment was given immediately after irradiation, the thermal enhancement ratio (TER) was higher in SDH than in SUH for tumors as well as the skin. A therapeutic gain factor (TGF) of 1.2 was obtained in SUH, while no therapeutic benefit was found in SDH. SDH was applied at various times (0 to 3 hr) before or after irradiation. When SDH was given before irradiation, the TER was consistently high to almost the same degree for tumors and the skin regardless of the time interval, resulting in minimal or no therapeutic gain. With SDH after irradiation, the TER for the skin decreased with increase in the time interval, while the TER for the tumor was moderately enhanced. Therefore, the TGF increased with increase in the time interval and reached 2.2 when SDH was given 3 hr after radiation. SUH is slightly advantageous over SDH in terms of the TGF, and SDH should be given 3 hr after irradiation when selective tumor heating is not possible. PMID- 3102441 TI - Medullasin stimulates the maturation of natural killer cells from human large granular lymphocytes. AB - Medullasin, a serine protease in bone marrow cells, has been shown to enhance human natural killer cell activity by acting directly on large granular lymphocytes. In the present report the mechanism of activation of natural killer cells by medullasin was studied by employing a single cell assay method in agar. Medullasin enhanced the target-binding capacity of lymphocytes, but the percentage of target-binding cells with dead target remained essentially unchanged. The maximum recycling capacity of natural killer cells was also increased by the treatment with medullasin. These results indicate that medullasin in granulocytes stimulates the maturation of natural killer cells with elevated recycling capacity from human large granular lymphocytes. PMID- 3102442 TI - Augmentation by priming with interferon-gamma of the binding of a muramyl dipeptide derivative to macrophages resulting in synergistic macrophage activation. AB - Macrophage (MA) activation by recombinant murine interferon-gamma (rMuIFN-gamma) and a synthetic muramyl dipeptide derivative, N alpha-(N-acetylmuramyl-L-alanyl-D isoglutaminyl)-N epsilon-stearoyl-L-lysine [MDP-Lys(L18)], was examined. The cytostatic activity of MA that had been primed with rMuIFN-gamma against Lewis lung adenocarcinoma cells was augmented extensively by exposure to MDP-Lys(L18) for a minimum of 15 min, though such treatment in the reverse sequence interfered with the effects of rMuIFN-gamma on MA. The binding assays revealed that rMuIFN gamma bound to MA with an apparent dissociation constant (Kd) of 0.93 X 10(-9) M (16,000 binding molecules/cell), while MDP-Lys(L18) bound nonspecifically and was endocytosed by MA at 37 degrees. The amount of MDP-Lys(L18) bound to the rMuIFN gamma-primed MA was significantly greater than that bound to the MA without rMuIFN-gamma priming. A small increase in the amount of MDP-Lys(L18) associated with MA was also observed at 4 degrees, but the amount was one order of magnitude less than that at 37 degrees. The binding of rMuIFN-gamma to MA was significantly suppressed by priming with MDP-Lys(L18). These results indicate that the binding of rMuIFN-gamma in preference to MDP-Lys(L18) to MA is of great importance in the mechanisms of MA activation. PMID- 3102443 TI - In vitro synergistic effects of natural human tumor necrosis factor and natural human interferon-alpha. AB - Tumor necrosis factor and interferons are multifunctional cytokines. The present studies were undertaken to investigate the biologic interactions of highly purified natural human tumor necrosis factor and highly purified natural human interferon-alpha, which were derived from a B cell acute lymphatic leukemia line (BALL-1 cells) sensitized with hemagglutinating virus of Japan (HVJ). Combined treatment with natural human tumor necrosis factor and natural human interferon alpha synergistically inhibited the in vitro proliferation of P4788 cells derived from a human colon cancer. Flow cytometric analysis of the cell cycle of asynchronous cells indicated that target cells treated with natural human tumor necrosis factor alone accumulate in the S phase. This accumulation in the S phase of the cell cycle was augmented by combined treatment with natural human tumor necrosis factor and natural human interferon-alpha. The growth inhibitions appeared to be a result of arrest in the S phase of the cell cycle. Combined treatment with these cytokines had potent cytostatic and cytotoxic effects on most of the tested malignant cell lines of human epithelial origin. PMID- 3102444 TI - Poultry offal ensiled with lactobacillus acidophilus for growing and finishing swine diets. AB - Poultry offal (heads, feet, viscera) from a broiler processing plant was ground and mixed with corn, dried molasses and a Lactobacillus acidophilus culture. Fermentation was shown to be effective in batch sizes of 3.8, 75.7 and 208.1 liters, as well as a 1,360-kg silo. It was generally complete at 72 h. In trial 1, rats were fed silage mixtures of 60:30:5:5, 45:45:5:5 and 30:60:5:5, offal, corn, molasses and inoculant, respectively. Rats did not gain as well when fed the silage diets (P less than .05) as when fed the basal diet; however, the ranking of silages was 45:45, 60:30 and 30:60, offal-to-corn ratio for rat daily gains and feed conversions. In trial 2, growing-finishing pigs were fed the 60:30:5:5 silage at rates of 0, 10, 20 and 30% of the diet. Average daily gains and feed-to-gain ratios were not affected by including offal silage at up to 20% of the diet, but 30% offal silage in diets resulted in depressed gains (P less than .05) and increased feed-to-gain ratios. Carcasses were not different among treatments for dressing percentage, length, average backfat and percentage of ham, loin, shoulder, lean cuts and primal cuts. Carcasses from pigs fed 20 and 30% offal silage had significantly darker and firmer loin-eyes than those from control fed pigs. Marbling was higher (P less than .05) in loin-eyes from pigs fed 30% offal silage as compared with those from pigs fed 0% offal silage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102445 TI - Secretion of luteinizing hormone and follicle stimulating hormone in intact and ovariectomized mares in summer and winter. AB - Sequential samples of blood were drawn via jugular catheters every 15 min for 24 h from four mares in each of five reproductive states: intact anestrous mares in winter, intact diestrous mares in summer, intact estrous mares in summer, ovariectomized mares in winter and ovariectomized mares in summer. Estrous mares were sampled on d 4 or 5 of estrus and diestrous mares on d 10 or 11 of diestrus. Each sample of plasma was assessed for concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) in two independent radioimmunoassays. A computer program was developed that determined peak hormone concentrations based on assay sensitivity, assay variability and repeatability of peaks in both independent assays. Peaks in LH and FSH were observed for mares in all five reproductive states, except for FSH concentrations in estrous mares. High frequency peaks of short duration were observed only in ovariectomized mares. Low frequency peaks of relatively long duration were observed in both intact and ovariectomized mares in both seasons. With the exception of estrous mares, there was variation among mares in the patterns of LH and(or) FSH within any one group; all estrous mares exhibited high, variable LH concentrations and low, constant FSH concentrations. In general, peaks in both gonadotropins occurred simultaneously. Ovariectomized mares exhibited more (P less than .05) peaks/24 h than intact mares for both gonadotropins. Ovariectomized mares also exhibited more (P less than .05) FSH peaks/24 h in summer than in winter. PMID- 3102446 TI - Intrinsic antibiotic resistance of Pseudomonas aeruginosa. PMID- 3102447 TI - Interactions of antimicrobial agents and antineoplastic agents. AB - The in-vitro interactions of four antimicrobial agents (piperacillin, dibekacin, minocycline, norfloxacin) and four antineoplastic agents (mitomycin C, bleomycin, doxorubicin, 5-fluorouracil) were examined by the chequerboard dilution method using 108 clinical isolates of four species of Gram-negative bacilli. Among the antimicrobial agents, piperacillin showed the greatest degree of synergism and norfloxacin the least. The frequency of synergism was essentially similar among the antineoplastic agents, although 5-fluorouracil was more frequently synergistic than other antineoplastic agents against Pseudomonas aeruginosa. Among the four species, synergism was most frequently shown against Proteus vulgaris and least against Escherichia coli. Antagonism was rarely seen. PMID- 3102448 TI - In-vitro study of the activity of ciprofloxacin combined with amikacin or ceftazidime against Pseudomonas aeruginosa. PMID- 3102449 TI - Emergence of ciprofloxacin-resistant Pseudomonas aeruginosa after combined therapy with ciprofloxacin and amikacin. PMID- 3102450 TI - The effect of imipenem/cilastatin on the aerobic faecal flora of children. AB - In 18 children treated with imipenem iv, quantitative cultures for aerobic faecal flora were performed on selective media (before, when possible, during and after treatment). In ten children who had not received previous antibiotic therapy, susceptible enterobacteria could be detected at a normal level throughout treatment. Eight children had received other antibiotics beforehand; during the first week of imipenem therapy, enterobacteria were undetectable in two and at low levels in three patients. In one patient previously treated with aztreonam, a strain of Pseudomonas aeruginosa became resistant to imipenem and increased in numbers. No dramatic change could be detected in group D streptococci, staphylococci or candida. The surprisingly small effect of imipenem on faecal Enterobacteriaceae could be explained by its inconstant presence in stools at the dose administered. PMID- 3102451 TI - The effects on beta-lactam susceptibility of phenotypic induction and genotypic derepression of beta-lactamase synthesis. AB - We have compared the ability of beta-lactam antibiotics to induce beta-lactamase synthesis and antagonize the in-vitro activity of other beta-lactams and also to select mutants with derepressed beta-lactamase synthesis amongst representative Gram-negative bacilli that produce inducible beta-lactamases. Both imipenem and cefoxitin were potent inducers of beta-lactamase and were able to antagonize the activity of other beta-lactams against isolates of Enterobacter cloacae, Citrobacter freundii and Pseudomonas aeruginosa when the two beta-lactams were present simultaneously. However, there was no antagonism for any compound against any of the organisms when the imipenem or cefoxitin was removed immediately before susceptibility to the other compounds was measured. Cefotaxime was a less potent inducer of beta-lactamase and failed to antagonize the activity of other compounds, even when present concurrently with them. Neither imipenem nor cefoxitin induced beta-lactamase synthesis in a strain of Escherichia coli, nor did they antagonize the activity of other beta-lactams against this strain. Imipenem was compared with cefotaxime and cefoxitin as an agent for the selection of beta-lactam-resistant variants. Resistant variants were obtained from isolates of Ent. cloacae, C. freundii and P. aeruginosa when cefotaxime or cefoxitin was used as the selective agent. Most of them synthesized beta-lactamase constitutively and showed reduced susceptibility to a wide range of beta-lactams, but not to imipenem. Variants with reduced susceptibility to imipenem were obtained only from the two isolates of P. aeruginosa. They did not show cross resistance to other beta-lactams and were not distinguishable from the parent strains in beta-lactamase production. PMID- 3102452 TI - Antibacterial properties of imipenem with special reference to the activity against methicillin-resistant staphylococci, cefotaxime-resistant Enterobacteriaceae and Pseudomonas aeruginosa. AB - Imipenem was examined with standardized agar dilution procedures against a wide range of bacteria. Geometric mean MICs against the genera Escherichia, Klebsiella, Enterobacter, Citrobacter and Serratia were 0.1-0.4 mg/l, and Proteus and Providencia spp. were inhibited by 0.25-4 mg/l. Acinetobacter calcoaceticus var. anitratum strains were inhibited by concentrations ranging from 0.12-0.5 mg/l. Methicillin-susceptible staphylococci were highly susceptible to the drug (MICs: less than or equal to 0.03 mg/l) and enterococci were inhibited by 0.25-16 mg/l. Most of the multi-resistant JK corynebacteria were resistant to imipenem. Imipenem was more active than any other beta-lactam against methicillin-resistant staphylococci; this was also demonstrated in a population analysis. Imipenem resistant minorities in populations, however, were also observed. Cefotaxime resistant and -intermediate Enterobacter and Citrobacter strains were inhibited by concentrations of 0.5 mg/l or less. No third-generation cephalosporin nor any other beta-lactam showed similarly high activity against these groups of organisms. Among 20 ceftazidime-resistant and 20 ceftazidime-susceptible isolates of Pseudomonas aeruginosa, no strain was resistant and only five ceftazidime resistant strains were intermediately susceptible (MIC, 8 mg/l) to imipenem. PMID- 3102453 TI - The pharmacokinetics and tissue penetration of imipenem. AB - Two studies were performed to investigate the penetration of imipenem into chemically induced inflammatory exudate and into peritoneal fluid. In the first study six volunteers received 500 mg of imipenem, alone and with 500 mg cilastatin. Little difference was noted in the pharmacokinetics or inflammatory fluid penetration of imipenem when given with or without cilastatin. The only significant alteration was the urine recovery (an increase from a mean of 14.7% to 55.6% in the presence of the enzyme inhibitor). The mean inflammatory fluid level of imipenem at 30 min was 6.2 mg/l (or 35% of the plasma level). The inflammatory fluid levels exceeded the plasma levels after 2 h. The overall penetration of imipenem/cilastatin into inflammatory fluid was 67.8% (+/- 13.8) and imipenem alone 73.2% (+/- 13.9). The mean elimination half-life of imipenem from plasma was 1.1 h and from inflammatory fluid 1.4 h (with or without cilastatin). In the second study, 29 patients received 1 g imipenem plus cilastatin before elective surgery and plasma and peritoneal levels were measured over 4 h. There was considerable penetration of the peritoneum, imipenem levels in excess of 30 mg/l being found 15 min after administration declining to 5-7 mg/l by 3-4 h. The mean percentage penetration was 73.4% (+/- 22.1). A brief review of the literature on imipenem tissue penetration is included. PMID- 3102455 TI - Blindness--a rare post-ictal phenomenon. PMID- 3102454 TI - Specific antigen and organelle expression of a long-term rhesus endothelial cell line. AB - A long-term culture of a spontaneously transformed endothelial cell line derived from the choroid-retina of a rhesus macaque fetus is reported. It has been carried in vitro by serial propagation more than 548 passages in 17 yr. Cells were identified as being of endothelial origin by cellular morphology, growth pattern, ultrastructure, immunocytochemistry (immunofluorescence and immunoperoxidase), and immunodiffusion. The transformants are characterized by an infinite life span, a changed expression of Factor VIII-related antigen, and chromosomal aberrations. Throughout long-term serial passages and after repeated freeze-storage, thawing, and reculture the cells retain the specific organelles, Weibel-Palade bodies, and most of the other characteristic morphologic features. For this long-term cultured endothelial cell line, Weibel-Palade bodies seem to be a more reliable marker than Factor VIII-related antigen. PMID- 3102456 TI - Nitrogen starvation mediated by DL-7-azatryptophan in the cyanobacterium Anabaena sp. strain CA. AB - The addition of DL-7-azatryptophan (AZAT), a tryptophan analog, to continuous cultures of Anabaena sp. strain CA grown with 10 mM nitrate as the nitrogen source resulted in the differentiation of heterocysts. Analysis of the intracellular amino acid pools of Anabaena sp. strain CA after the addition of AZAT showed a marked decline in the intracellular glutamate pool and a slight increase in the levels of glutamine. The in vitro activity of glutamate synthase, the second enzyme involved in primary ammonia assimilation in Anabaena spp., was partially inhibited by the presence of AZAT at concentrations which are effective in triggering heterocyst formation (15% inhibition at 10 microM AZAT and up to 85% inhibition at 1.0 mM AZAT). Azaserine, a glutamine analog and potent glutamate synthase inhibitor, had no effect on the triggering of heterocyst development from undifferentiated batch and continuous cultures of Anabaena sp. strain CA. However, the presence of 1.0 microM azaserine significantly decreased the intracellular glutamate pool and increased the glutamine pool. The addition of AZAT also caused a decrease in the C-phycocyanin content of Anabaena sp. strain CA as a result of its proteolytic degradation. AZAT also had an inhibitory effect on the nitrogenase activity of Anabaena sp. strain CA. All these results suggest that AZAT causes a general nitrogen starvation of Anabaena sp. strain CA filaments, triggering heterocyst synthesis. PMID- 3102459 TI - Occurrence in Bacillus megaterium of uridine 5'-diphospho-N-acetylgalactosamine and uridine 5'-diphosphogalactosamine, intermediates in the biosynthesis of galactosamine-6-phosphate polymer. AB - We isolated two galactosamine derivatives from Bacillus megaterium sporulating cells by lectin affinity chromatography followed by DEAE-Sephadex A-25 chromatography. From chemical analyses and measurements of these compounds, it was determined that one was uridine 5'-diphospho-N-acetylgalactosamine and that the other was uridine 5'-diphosphogalactosamine. They appeared in the middle stage of sporulation and disappeared during the period when galactosamine-6 phosphate is deposited on the forespore surface. These results suggest that uridine 5'-diphospho-N-acetylgalactosamine and uridine 5'-diphosphogalactosamine are intermediates in the biosynthesis of the galactosamine-6-phosphate polymer, a backbone structure of the exosporium. PMID- 3102457 TI - Regulation of spo0H, an early sporulation gene in bacilli. AB - The construction of lacZ fusions in frame with the spo0H gene of Bacillus licheniformis enabled us to study the expression of this gene under various growth conditions and in various genetic backgrounds. spo0H was expressed during vegetative growth, but the levels increased during early stationary phase and then decreased several hours later. Expression of the gene was not repressed by glucose, but was induced by decoyinine, an inhibitor of guanine nucleotide biosynthesis, which can induce sporulation. Of those tested, the only spo0 gene required for the expression of spo0H was spo0A, and this requirement was eliminated by the abrB mutation, a partial suppressor of spo0A function. spo0H lacZ expression was much higher in a strain with a deletion in the spo0H gene. PMID- 3102458 TI - In vitro expression of a Tn9-derived chloramphenicol acetyltransferase gene fusion by using a Bacillus subtilis system. AB - A coupled in vitro protein-synthesizing system has been developed with components derived totally from Bacillus subtilis. The system synthesized specific gene products from various exogenous DNA templates, including B. subtilis phage phi 29, plasmid pUB110, and a heterologous B. subtilis-Escherichia coli gene fusion containing the transposon Tn9-derived chloramphenicol acetyltransferase (cat) gene. The gene fusion product was able to show CAT activity, bind specifically to a Sephacryl-chloramphenicol column, and react immunologically against anti-CAT antiserum. The fidelity of this in vitro system was demonstrated by the synthesis of gene products identical to that made in vivo. We suggest that this system may be used to study the regulation of gene expression in vitro. PMID- 3102460 TI - Cloning and transcriptional regulation of the elastase lasA gene in mucoid and nonmucoid Pseudomonas aeruginosa. AB - The lasA gene (whose product is involved in the production of extracellular elastolytic activity) was isolated from a genomic bank containing DNA from Pseudomonas aeruginosa FRD1. Recombinant plasmid pELA1, containing the lasA gene, complemented the temperature-sensitive elastase mutation (lasA1) in P. aeruginosa PAO-E64. The lasA gene was physically mapped on plasmid pELA1 by deletion analysis and transposon mutagenesis. The direction of transcription of lasA was determined with a promoterless chloramphenicol acetyltransferase cartridge. The lasA-chloramphenicol acetyltransferase plasmid was transferred to isogenic mucoid and nonmucoid strains of P. aeruginosa FRD; the transcription of lasA chloramphenicol acetyltransferase was slightly higher in the nonmucoid strain. PMID- 3102462 TI - Complete heart block associated with mesoridazine and lithium combination. PMID- 3102463 TI - Roles of lysine1 and lysine7 residues of bovine pancreatic ribonuclease in the enzymatic activity. AB - In order to investigate the roles of Lys1 and Lys7 of RNase A in the enzymatic activity, four S-peptide derivatives were prepared and their abilities to activate S-protein were measured. They are 1-norleucine-S-peptide, 7-norleucine S peptide, 1,7-di-norleucine-S-peptide, and tri-N-acetyl S-peptide. From the analyses of the relative activity and kinetic parameters of RNase S' derivatives with UpU, UpU greater than p, and UpUpU greater than p, it was concluded that Lys7 of RNase A is a binding site for 3'-phosphate of UpU greater than p and the modification or substitution of Lys1 affects the binding of trinucleotide substrate. PMID- 3102461 TI - Lipoteichoic acid from Bacillus subtilis subsp. niger WM: isolation and effects on cell wall autolysis and turnover. AB - Lipoteichoic acid (LTA) was extracted by means of hot aqueous phenol from Bacillus subtilis subsp. niger WM cells grown under various conditions in chemostat culture. The extracts were partially purified by nuclease treatment and gel permeation chromatography. Chemical analyses revealed a composition consistent with a polyglycerol phosphate polymer. The influence on autolysis of the LTAs thus obtained was studied with both whole cells and autolysin-containing native walls of B. subtilis subsp. niger WM. Lysis rates of phosphate-limited cells could be reduced to about 40% of the control rate by the addition of LTA, whereas lysis of cells grown under phosphate-sufficient conditions was affected to a much lesser extent. The lysis of native walls prepared from variously grown cells proved to be fairly insensitive to the addition of LTA. The effect of LTA on wall turnover was studied by following the release of radioactively labeled wall material during exponential growth. The most obvious effect of LTA was a lowered first-order rate of release of labeled wall material; calculations according to the model for cell wall turnover in Bacillus spp. formulated by De Boer et al. (W. R. De Boer, F. J. Kruyssen, and J. T. M. Wouters, J. Bacteriol. 145:50-60, 1981) revealed changes in wall geometry and not in turnover rate in the presence of LTA. PMID- 3102464 TI - Purification and some properties of short chain-length specific trans-2-enoyl-CoA reductase in mitochondria of Euglena gracilis. AB - Short chain-length specific trans-2-enoyl-CoA reductase (reductase I), which contributed to mitochondrial fatty acid synthesis, was purified about 200-fold from crude extract of mitochondria in Euglena gracilis. It had a molecular weight of 39,000, and consisted of two dissimilar subunits with molecular weights of 15,000 and 25,000. The enzyme utilized crotonyl-CoA as the most active substrate and showed negative cooperativity in the reaction with the substrate. NADH was the sole electron donor. Some divalent cations were inhibitory to the enzyme when incubated with the enzyme prior to the start of the reaction. The reductase apparently contained loosely bound FAD. PMID- 3102465 TI - Purification of a protein kinase phosphorylating myosin regulatory light chain-a (RLC-a) from smooth muscle of scallop, Patinopecten yessoensis. AB - A protein kinase activity phosphorylating regulatory light chain-a (RLC-a) of scallop smooth muscle myosin was found to be present in scallop smooth muscle homogenate. The kinase was purified to homogeneity and named RLC-a myosin kinase (aMK). aMK was extracted from the muscle homogenate with a low salt solution and was purified by successive DE-32 ion exchange chromatography, gel filtration on Ultrogel AcA 44, and affinity chromatography on Sepharose 4B-6-aminohexyl-1 pyrophosphate. The molecular weight of aMK was estimated to be 40-kDa from the mobility on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and 35-kDa from the elution volume on Sephadex G-150 gel filtration. The phosphorylation site of RLC-a by aMK was determined to be Ser residue(s). Only RLC-a was phosphorylated; the other regulatory light chain, RLC-b, was not. The phosphorylatable Ser of RLC-a is, therefore, considered to be Ser-11, which is located in the N-terminal region having a different amino acid sequence from that of RLC-b. RLC-a was phosphorylated by aMK 3 times faster in the free state than in the bound state to myosin. aMK does not require calmodulin and is rather inhibited by CaCl2. PMID- 3102466 TI - Equilibrium and kinetic studies on the binding of gluconolactone to almond beta glucosidase in the absence and presence of glucose. AB - The binding of glucono-1,5-lactone (gluconolactone) with almond beta-glucosidase was studied at pH 5.0 and 25 degrees C, in the absence and presence of glucose, by monitoring the enzyme fluorescence as a probe. From the results of fluorometric titration, the dissociation constant Kd and the maximum fluorescence intensity increase (percent) of the enzyme-gluconolactone complex relative to the enzyme alone, delta Fmax, were determined to be 12.7 microM and 14.7%, respectively. From the study of the temperature dependence of Kd, delta G degrees, delta H degrees and delta S degrees for the binding were evaluated to be -6.7 kcal mol-1, -3.5 kcal mol-1, and 10.8 e.u. (cal mol-1 deg-1), respectively, at 25 degrees C. The analysis of the fluorometric titration data in the presence of glucose revealed that these ligands bind competitively to the enzyme, probably at the same site. The results of a stopped-flow kinetic study are consistent with the following two-step mechanism: (formula; see text) which indicates that gluconolactone (L) and the enzyme (E) transiently form a loosely bound complex, ELtr (k-1/k+1 = 4.5 mM), in the first rapid bimolecular association step, and ELtr is converted into a more tightly bound complex EL (k+2 = 94 s-1, k-2 = 0.36 s-1) in the subsequent slow unimolecular process. The fluorescence intensity increase occurs solely in the latter step. PMID- 3102467 TI - Calmodulin is labeled at lysine 148 by a chemically reactive phenothiazine. AB - 10-(3-Propionyloxysuccinimide)-2-(trifluoromethyl)phenothiazine (POS-TP) is a chemically reactive calmodulin antagonist: 2 mol are incorporated per mol of calmodulin when excess reagent is used, and only lysyl side chains are modified. Tryptic peptide mapping demonstrated that a single unique site on calmodulin reacts at low molar ratios of POS-TP. Labeled peptides were isolated and analyzed by amino acid composition and sequence analysis. The unique site was identified as Lys148 of calmodulin, the carboxyl-terminal residue. At higher molar ratios of the reagent Lys21, Lys75, and Lys77 are labeled as are several minor peptides that were not characterized. PMID- 3102468 TI - Identification and characterization of a heterogeneous population of growth hormone receptors in mouse hepatic membranes. AB - Covalent cross-linking of radiolabeled mouse growth hormone (125I-mGH) with the homobifunctional cross-linking agent bis(sulfosuccinimidyl)suberate (BS3) to microsomal membranes prepared from late pregnant mouse liver resulted in the labeling of three specific mGH binding proteins (receptors) with apparent Mr = 125,000, 62,000, and 56,000, as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. These same three specifically labeled proteins were present, but with slightly lower apparent molecular weights, when samples were electrophoresed in the absence of reductant. Cross linking of 125I-mGH to plasma membrane-enriched fractions of late pregnant mouse liver resulted only in the specific labeling of the two lower molecular weight receptors. Removal of all N-linked carbohydrate with peptide: N-glycosidase F resulted in decreasing the apparent molecular weights of the three receptor forms to 110,000, 50,000, and 46,000 for the 125,000, 62,000, and 56,000 molecular weight forms of the receptor, respectively. Smaller decreases in the molecular weights of all three receptor forms were also apparent after treatment with neuraminidase. However, the differences seen in the intact forms of the growth hormone receptor were also present in the deglycosylated receptors. The relationship between the three forms of the growth hormone receptor was further investigated by comparing the fragments produced by proteolytic digestion of the cross-linked receptors with Staphylococcus aureus protease and endoproteinase Lys C. The fragments produced from all three receptor forms had very similar molecular weights, although there were slight molecular weight differences in the fragments produced by endoproteinase Lys-C digestion. The overall similarity of the fragments produced by the proteolytic digestions suggests that the three forms of the receptor are related. PMID- 3102469 TI - Differential hydrolysis of phospholipid molecular species during activation of human platelets with thrombin and collagen. AB - Mass changes in the various molecular species of phospholipids were determined after stimulation of human platelets with thrombin and collagen. Upon stimulation, every molecular species of phosphatidylinositol and phosphatidylserine was equally hydrolyzed, whereas the molecular species of phosphatidylcholine and diacyl- and alkenylacylphosphatidylethanolamine containing arachidonic acid were selectively hydrolyzed. At low Ca2+ concentrations, which result from mobilization of intracellular Ca2+ stores, phosphatidylinositol, phosphatidylcholine, and diacylphosphatidylethanolamine were hydrolyzed after stimulation with thrombin, whereas only phosphatidylinositol was hydrolyzed with production of thromboxane B2 after stimulation with collagen. At high Ca2+ concentrations, phosphatidylcholine and diacylphosphatidylethanolamine were hydrolyzed after stimulation with collagen, and phosphatidylserine and alkenylacylphosphatidylethanolamine were degraded after stimulation with both thrombin and collagen. [1-14C]Arachidonic acid was heterogeneously incorporated into the individual molecular species of the various phospholipid classes, indicating that the determination of mass is essential for an accurate picture of phospholipid hydrolysis. The data reported here indicate that the Ca2+ concentration affects the differential degradation of phospholipid molecular species in activated human platelets. PMID- 3102470 TI - Hormonal regulation of tissue plasminogen activator secretion and mRNA levels in rat granulosa cells. AB - Granulosa cells from immature rats produce tissue plasminogen activator (tPA) in response to follicle stimulating hormone (FSH) or luteinizing hormone (LH) both in vitro and in vivo. We have used the in vitro system to investigate the level at which the hormonal induction of tPA is regulated. Within 12 h following FSH addition, a dramatic but transient increase in tPA secretion occurs for by 24 h secretion returns to basal levels. This pattern of enzyme induction is similar with LH, but the onset of the increase is delayed. When steady-state tPA mRNA levels are examined after hormone treatment, the results mirror those obtained if one measures enzyme activity; a large increase in tPA mRNA followed by a decrease to basal levels is observed with both hormones, and the lag in induction by LH is also apparent. These results demonstrate that the regulation of tPA activity by gonadotropins occurs at the level of the steady-state concentration of the mRNA. In the presence of cycloheximide, the induction of tPA mRNA by FSH or LH is not greatly affected, indicating that this phase of the response to gonadotropins does not require the synthesis of new protein. However, the decrease in tPA mRNA levels observed 24 h after FSH treatment is affected by cycloheximide, in that the drug delays the reduction in mRNA levels seen with hormone alone. PMID- 3102471 TI - Interaction of GTP-binding regulatory proteins with chemosensory receptors. AB - GTP-binding regulatory proteins (G-proteins) were identified in chemosensory membranes from the channel catfish, Ictalurus punctatus. The common G-protein beta-subunit was identified by immunoblotting in both isolated olfactory cilia and purified taste plasma membranes. A cholera toxin substrate (Mr 45,000), corresponding to the G-protein that stimulates adenylate cyclase, was identified in both membranes. Both membranes also contained a single pertussis toxin substrate. In taste membranes, this component co-migrated with the alpha-subunit of the G-protein that inhibits adenylate cyclase. In olfactory cilia, the Mr 40,000 pertussis toxin substrate cross-reacted with antiserum to the common amino acid sequence of G-protein alpha-subunits, but did not cross-react with antiserum to the alpha-subunit of the G-protein from brain of unknown function. The interaction of G-proteins with chemosensory receptors was determined by monitoring receptor binding affinity in the presence of exogenous guanine nucleotides. L-Alanine and L-arginine bind with similar affinity to separate receptors in both olfactory and gustatory membranes from the catfish. GTP and a nonhydrolyzable analogue decreased the affinity of olfactory L-alanine and L arginine receptors by about 1 order of magnitude. In contrast, the binding affinities of the corresponding taste receptors were unaffected. These results suggest that olfactory receptors are functionally coupled to G-proteins in a manner similar to some hormone and neurotransmitter receptors. PMID- 3102473 TI - HPr/HPr-P phosphoryl exchange reaction catalyzed by the mannitol specific enzyme II of the bacterial phosphotransferase system. AB - The mannitol specific Enzyme II of the phosphoenolpyruvate: sugar phosphotransferase system of Escherichia coli catalyzes an exchange reaction in which a phosphoryl moiety is transferred from one molecule of the heat stable phosphocarrier protein HPr to another. An assay was developed for measuring this reaction. Unlabeled phospho-HPr and 125I-labeled free HPr were incubated together in the presence of Enzyme IImtl, and production of 125I-labeled phospho-HPr was measured. The reaction was concentration-dependent with respect to Enzyme IImtl and did not occur in its absence. The reaction occurred in the absence of Mg2+ in the presence of 10 mM EDTA. Treatment of Enzyme IImtl with the histidyl reagent diethylpyrocarbonate inactivated it with respect to the exchange reaction. Levels of N-ethylmaleimide which inactivate Enzyme IImtl with respect to both P enolpyruvate-dependent phosphorylation of mannitol and mannitol/mannitol-1-P transphosphorylation did not affect its activity in the exchange reaction; however, treatment with another sulfhydryl reagent, p-chloromercuribenzoate, resulted in partial inactivation. The pH optimum for the Enzyme IImtl-catalyzed exchange reaction was about 7.5. Enzyme I and the glucose specific Enzyme III, two other E. coli phosphotransferase system proteins which, like Enzyme IImtl, interact directly with HPr, were also shown to catalyze 125I-HPr/HPr-P phosphoryl exchange. PMID- 3102472 TI - Compartmentation of 14CO2 in the perfused rat liver. AB - The specific activity of the mitochondrial CO2 + bicarbonate system has been measured in perfused livers using the specific activities of urea and acetoacetate derived from 2-ketoisocaproate catabolism. Label was supplied either as NaH14CO3, 2-keto[1-14C]isocaproate, [1-14C]pyruvate, [1-14C]glutamine, or [14C]formate. With labeled bicarbonate, pyruvate, or 2-ketoisocaproate, the specific activities of effluent bicarbonate, urea, and acetoacetate were equal (acetoacetate was labeled only on C-1). In the presence of [14C]formate, the specific activity of acetoacetate was double that of urea. Acetazolamide (0.2 mM), an inhibitor of carbonic anhydrase, decreased the specific activities of urea and acetoacetate labeled from NaH14CO3 and increased the specific activities of urea and acetoacetate labeled from the other tracers. We conclude that: acetoacetate derived from 2-ketoisocaproate is, like urea, an index of the specific activity of mitochondrial CO2 in liver, carbonic anhydrase activity equalizes the specific activities of the CO2 + bicarbonate system on both sides of the mitochondrial membrane, and a fraction of [14C] formate-derived 14CO2 appears to be generated in a mitochondrial compartment, in the close vicinity of methylcrotonyl-CoA carboxylase. PMID- 3102474 TI - Linoleate metabolites enhance the in vitro proliferative response of mouse mammary epithelial cells to epidermal growth factor. AB - Linoleic acid, arachidonic acid, prostaglandin E1, and prostaglandin E2 stimulated the proliferation of mammary epithelial cells in serum-free primary cultures only in the presence of epidermal growth factor. Linoleate-stimulated growth was manifest later in culture when proliferation, initiated by epidermal growth factor only, reached a plateau while linoleate-supplemented epidermal growth factor cultures continued to proliferate. The cultures in the plateau phase of growth could be restimulated to grow by adding either linoleic acid or prostaglandin E2 to the media. While the linoleate response could be abolished by the cyclooxygenase inhibitor, indomethacin, prostaglandin E2-stimulated growth remained unaffected. Linoleic acid was metabolized to arachidonic acid and prostaglandin E2, both in the growing and resting cultures. Proliferating cells metabolized linoleate and prostaglandin E2 extensively so that neither the fatty acid nor prostaglandin E2 accumulated in large quantities in the proliferating cultures. The concentrations of prostaglandin E2 in growing cultures supplemented with linoleic acid were much higher than in cultures without it. These results suggest that the metabolism of linoleic acid leading to prostaglandin production, not its contribution to membrane polyunsaturation, is necessary for sustained growth of mammary epithelial cells in the presence of epidermal growth factor. PMID- 3102475 TI - Characterization of the microtubule movement produced by sea urchin egg kinesin. AB - We have used an in vitro assay to characterize some of the motile properties of sea urchin egg kinesin. Egg kinesin is purified via 5'-adenylyl imidodiphosphate induced binding to taxol-assembled microtubules, extraction from the microtubules in ATP, and gel filtration chromatography (Scholey, J. M., Porter, M. E., Grissom, P. M., and McIntosh, J. R. (1985) Nature 318, 483-486). This partially purified kinesin is then adsorbed to a glass coverslip, mixed with microtubules and ATP, and viewed by video-enhanced differential interference contrast microscopy. The microtubule translocating activity of the purified egg kinesin is qualitatively similar to the analogous activity observed in crude extracts of sea urchin eggs and resembles the activity of neuronal kinesin with respect to both the maximal rate (greater than 0.5 micron/s) and the direction of movement. Axonemes glide on a kinesin-coated coverslip toward their minus ends, and kinesin coated beads translocate toward the plus ends of centrosome microtubules. Sea urchin egg kinesin is inhibited by high concentrations of SH reagents ([N ethylmaleimide] greater than 3-5 mM), vanadate greater than 50 microM, and [nonhydrolyzable nucleotides] greater than or equal to [MgATP]. The nucleotide requirement of sea urchin egg kinesin is fairly broad (ATP greater than GTP greater than ITP), and the rate of microtubule movement increases in a saturable fashion with the [ATP]. We conclude that the motile activity of egg kinesin is indistinguishable from that of neuronal kinesin. We propose that egg kinesin may be associated with microtubule-based motility in vivo. PMID- 3102476 TI - Evidence for an intermediate methyl-acceptor for chemotaxis in Bacillus subtilis. AB - Bacillus subtilis responds to chemotactic attractants by demethylating certain membrane-bound proteins, termed methyl-accepting chemotaxis proteins (MCPs) and by augmenting the evolution of methanol. We propose that the methanol comes from a methylated intermediate rather than directly from the MCPs themselves. First, repellent blocks attractant-induced smooth swimming and methanol formation, but not MCP demethylation. Second, prior treatment of cells with much attractant to reduce radiolabeling of MCPs and increase that of the putative intermediate caused increased, rather than decreased, production of methanol upon addition and then removal of the repellent. Third, such cells also produced much, rather than little, methanol upon addition of less attractant than during the pretreatment. We speculate that unmethylated intermediate causes tumbling; attractant causes its methylation and hence absence of tumbling (smooth swimming). Its demethylation during the period of smooth swimming affords adaptation. PMID- 3102477 TI - Purification and mechanism of activation of a nerve growth factor-sensitive S6 kinase from PC12 cells. AB - A nerve growth factor (NGF)-sensitive S6 kinase was purified by alkaline lysis of PC12 cells. The activity in lysates from NGF-treated cells was 10-20-fold higher than that from controls. Half-maximal stimulation of the S6 kinase by NGF treatment occurred in approximately 5 min, and the activity returned almost to basal levels by 2 h. A rapid purification method was devised in which crude extract was applied directly to a PBE 94 column after buffer exchange on a PD-10 column (Sephadex G-25 M). The activated S6 kinase was purified at least 673-fold with a recovery of approximately 70%. The S6 kinase has an apparent molecular weight of 45,000 and is highly specific for S6. It is not inhibited by the specific inhibitor of cAMP-dependent protein kinases, or by chlorpromazine or sodium vanadate, nor is it activated by Ca2+/calmodulin. It was inhibited by EGTA, beta-glycerophosphate, or NaF. Phosphorylation occurred solely on serine residues. The S6 kinase activity from control cells and from NGF-treated cells eluted at pH 5.69 and 5.58, respectively, during PBE 94 column chromatography. Pretreatment of crude extract from NGF-stimulated cells with alkaline phosphatase resulted in an elution of the enzyme at the position of S6 kinase from control cells and a concomitant decrease in activity. These results indicate that phosphorylation is involved in the mechanism of S6 kinase activation. PMID- 3102478 TI - Rearranged coding segments, separated by a transfer RNA gene, specify the two parts of a discontinuous large subunit ribosomal RNA in Tetrahymena pyriformis mitochondria. AB - In the mitochondria of Tetrahymena pyriformis ST, the large subunit ribosomal RNA (LSU rRNA) is discontinuous, consisting of two species, alpha (280 nucleotides in length) and beta (approximately equal to 2.45 kilobases long). LSU alpha is the 5'-terminal portion (i.e. a 5.8 S-like rRNA), and LSU beta constitutes the rest of this LSU rRNA, as judged by both primary and secondary structure homology to other LSU rRNAs. Remarkably, LSU alpha is encoded downstream of LSU beta, the two genes being separated by a tRNALeu gene. This is the first demonstration of a discontinuous rRNA whose coding sequences are rearranged, deviating from the conventional, highly conserved, 5'----3' order of sequence domains in the LSU rRNA gene. This novel gene organization (5'-LSU beta-2-base pair spacer-tRNALeu 10-base pair spacer-LSU alpha) is identical in both copies of the subterminal inverted repeat in the linear T. pyriformis mitochondrial genome. Sequence heterogeneity in the LSU alpha transcript and its genes, together with Northern hybridization data, suggest that both copies of the inverted repeat are expressed. PMID- 3102479 TI - Structure of the gene encoding the circumsporozoite protein of Plasmodium yoelii. A rodent model for examining antimalarial sporozoite vaccines. AB - The gene encoding the circumsporozoite protein (CSP) from the rodent malaria parasite, Plasmodium yoelii, has been cloned and the nucleotide sequence has been determined. The gene encodes a protein of 367 amino acids as deduced from the nucleotide sequence. This gene is structurally similar to other Plasmodium spp. CSP genes in that it contains putative hydrophobic signal and anchor sequences at the NH2 and COOH termini, respectively, two small regions (Regions I and II) that are conserved in all CSP genes analyzed to date, and a central region containing the immunodominant repeating peptide sequence. Unlike other CSP genes, however, the immunodominant repeat region of the gene is composed of two distinctly different types of tandem repeats. One repeating unit is six amino acids (Gln-Gly Pro-Gly-Ala-Pro) in length while the other is only four (Gln-Gln-Pro-Pro) residues long. A synthetic peptide, Gln-Gly-Pro-Gly-Ala-Pro X 3, strongly inhibits the binding of anti-CSP monoclonal antibody to sporozoite antigens while another peptide, Gln-Gln-Pro-Pro X 4, weakly inhibits the binding of this same antibody to sporozoite antigens. This work should allow the construction of a mouse model system to parallel human vaccine trials. PMID- 3102480 TI - Epidermal growth factor stimulates the rapid accumulation of inositol (1,4,5) trisphosphate and a rise in cytosolic calcium mobilized from intracellular stores in A431 cells. AB - Exposure of A431 human epidermoid carcinoma cells to epidermal growth factor (EGF), bradykinin, and histamine resulted in a time- and concentration-dependent accumulation of the inositol phosphates (InsP) inositol monophosphate, inositol bisphosphate, and inositol trisphosphate (InsP3). Maximal concentrations of EGF (316 ng/ml; approximately 50 nM), bradykinin (1 microM), and histamine (1 mM) resulted in 3-, 6-, and 3-fold increases, respectively, in the amounts of inositol phosphates formed over a 10-min period. The K0.5 values for stimulation were approximately 10 nM, 3 nM, and 10 microM for EGF, bradykinin, and histamine, respectively. EGF and bradykinin stimulated the rapid accumulation of the two isomers of InsP3, Ins(1,3,4)P3, and Ins(1,4,5)P3 as determined by high performance liquid chromatography analysis; maximal accumulation of Ins(1,4,5)P3 occurred within 15 s. EGF and bradykinin also stimulated a rapid (maximal levels attained within 30 s after addition of hormone) and a sustained 4- and 6-fold rise, respectively, in cytosolic free Ca2+ levels as measured by Fura-2 fluorescence. EGF and bradykinin also produced a rapid, although transient, 3- and 5-fold increase, respectively, in cytosolic free Ca2+ after chelation of extracellular Ca2+ with 3 mM EGTA. These data are consistent with the idea that EGF elevates intracellular Ca2+ levels in A431 cells, at least in part, as a result of the rapid formation of Ins(1,4,5)P3 and the consequential release of Ca2+ from intracellular stores. PMID- 3102481 TI - The use of avidin-biotinylglycan as the model for in vitro glycoprotein processing. AB - In an attempt to evaluate the effects of the protein matrix on the specificity of glycoprotein processing in Golgi membranes, we have developed a model neoglycoprotein consisting of biotinylated glycans bound noncovalently to avidin (Chen, V. J., and Wold, F. (1986) Biochemistry 25, 939-444) with which the protein effect on processing can be evaluated as the difference in substrate efficiency between a free biotinylated glycan and the same biotinylated glycan bound to avidin. The avidin (streptavidin)-glycan complex stability was found to be proper for the experimental design; the complex remains intact for extended periods of incubation at the concentrations used, but the glycan can be completely liberated and recovered by heating the complex at 95 degrees C for 10 min in the presence of a 10-fold molar excess of biotin. By measuring the relative rates of [14C]sugar incorporation into the free and bound substrates it was demonstrated that the protein indeed influences the processing reactions; under conditions where free glycans such as biotinyl-Asn-Glc-NAc2-Man5 and 6 (biotinamido)hexanoyl-Asn-Glc-NAc2-Man5 could be converted to the biantennary products R-Asn-GlcNAc2-Man3-GlcNAc2-Gal2-sialyl2 in the presence of UDP-GlcNAc, UDP-Gal and CMP-sialic acid and Golgi enzymes, the avidin-bound derivative without the extension arm gave only low levels of product and the streptavidin bound one remained unaltered. The presence of the extension arm in the substrates significantly improved the yield of some products in the complex, apparently by reducing or eliminating the avidin inhibition of the early steps, but not of the late ones. There are consequently two types of effect of the protein matrix on processing efficiency. One is expressed only when the glycan is close to the protein surface and affecting primarily early steps (mannosidases and GlcNAc transferases). The other is apparently independent of the proximity of the glycan core and the protein, and affects primarily late steps, in particular the incorporation of the second sialic acid residue into a biantennary complex glycan. PMID- 3102482 TI - A study on the selective binding of apoprotein B- and E-containing human plasma lipoproteins to immobilized rat serum phosphorylcholine-binding protein. AB - Rat serum phosphorylcholine-binding protein (PCBP), a member of the pentraxin family of proteins, was previously shown to bind multilamellar liposomes prepared with egg phosphatidylcholine and lysophosphatidylcholine. The results suggested that the phosphorylcholine groups on the surface of liposomes play an important role in the binding process (Nagpurkar, A., Saxena, U., and Mookerjea, S. (1983) J. Biol Chem. 258, 10518-10523). A study on the binding of human plasma lipoproteins to PCBP immobilized on Sepharose has now been initiated. Very low density lipoproteins were partially bound to a Sepharose-PCBP column, and the bound fraction contained higher concentrations of apoprotein B and E. All the low density lipoproteins applied were bound to the column. In the case of high density lipoproteins, only a small fraction was retained on the column (based on protein analysis), and that bound fraction contained all the apoprotein E and Lp(a) lipoprotein. The binding of very low, low, and high density lipoproteins to Sepharose-PCBP was Ca2+-dependent, and the bound lipoproteins were quantitatively eluted by a phosphorylcholine gradient. Apoprotein B and E were also bound when whole human plasma was applied to Sepharose-PCBP. The effect of selective modification of lysine residues by acetoacetylation and of arginine residues by cyclohexanedione on the binding of low density lipoproteins to Sepharose-PCBP was examined. Modification of arginyl residues resulted in marked reduction of binding, whereas modification of lysine had no effect. Removal of sialic acid from PCBP also had no effect on the binding of low density lipoproteins to immobilized-desialylated PCBP column. The preferential binding of apoprotein B- and E-containing lipoproteins to Sepharose-PCBP indicates a possible physiological role of PCBP and other similar circulating phosphorylcholine binding proteins of the pentraxin family in lipoprotein metabolism. PMID- 3102483 TI - Thrombin interaction with platelets. Influence of a platelet protease nexin. AB - A fraction of the 125I-thrombin that binds to human platelets is taken into a sodium dodecyl sulfate-resistant 77 kDa complex with a platelet factor (Bennett, W. F., and Glenn, K. C. (1980) Cell 22, 621-627). Here we show that this platelet factor is in several respects similar to protease nexin I (PNI), a fibroblast thrombin inhibitor. The complexes are of the appropriate size, bind to Sepharose that has been derivatized with anti-PNI antibody, do not form when the thrombin active site has been blocked with diisopropylphosphofluoridate, and do not appear on platelets when heparin is present. However, the platelet factor does not bind urokinase, indicating that this "platelet PN" may be distinct from PNI. Following brief incubation with 125I-thrombin, platelet PN X 125I X thrombin complexes are found both associated with the platelets and free in the binding medium. 125I Thrombin has a higher affinity for platelet PN than for platelet receptors. In 30 s binding incubations carried out with thrombin at concentrations below 0.3 nM, formation of the 77-kDa complex accounts for most of the platelet specific binding of 125I-thrombin. Subtracting this large contribution to 125I-thrombin specific binding reveals that the reversible binding of 125I-thrombin to platelet receptors exhibits sigmoidal thrombin dose-dependence. Thrombin stimulation of platelet [14C]serotonin release exhibits similar thrombin dose dependence. These results indicate that platelets may possess a mechanism for suppressing their interaction with active thrombin at thrombin doses below 0.3 nM. It is possible that platelet PN carries out this function by capturing thrombin before thrombin binds to its signal-transmitting receptors. PMID- 3102484 TI - On experimental artifacts in the use of metal ion chelators for the determination of the cation binding constants of alpha-lactalbumin. A reply. AB - The binding constant of Ca2+ to the strong cation site of bovine alpha lactalbumin has been measured directly by monitoring the free calcium concentration by Quin 2 fluorescence. A dissociation constant of 1-4 nM was calculated, which confirms the strong calcium binding properties of this protein. In order to examine whether the metal ion chelators EDTA or EGTA affect the cation binding equilbria by binding to bovine alpha-lactalbumin, calcium binding equilibria were carefully measured under highly stabilized pH and temperature conditions. Within the concentration ranges required for competitive binding by these ligands (EDTA or EGTA) (less than 1-3 mM) these chelators produced no artifacts, in contradiction to the data of Kronman and Bratcher (Kronman, M. J., and Bratcher, S. C. (1983) J. Biol. Chem. 258, 5707-5709). PMID- 3102485 TI - Characterization of recombinant human factor VIII. AB - Recently, complete human factor VIII DNA clones have been obtained and subsequently expressed in baby hamster kidney cells (Wood, W. I., Capon, D. J., Simonsen, C. C., Eaton, D. L., Gitschier, J., Keyt, B., Seeburg, P. H., Smith, D. H., Hollingshead, P., Wion, K. L., Delwart, E., Tuddenham, E. G. D., Vehar, G. A., and Lawn, R. M. (1984) Nature 312, 330-337). The recombinant factor VIII (rVIII) protein secreted from these cells has now been purified allowing its structural analysis and comparison to plasma-derived factor VIII (pdVIII). Analysis of purified rVIII by sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that it consists of multiple polypeptides with relative mobilities (Mr) ranging from 80,000-210,000. The same pattern of polypeptides is also observed for pdVIII resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The proteins associated with rVIII are recognized by pdVIII antibodies in a Western blot. When rVIII and pdVIII are subjected to isoelectric focusing they are resolved into a similar pattern of protein bands. Thrombin, factor Xa, and activated protein C, which modulate factor VIII activity by proteolysis, process rVIII in the same manner they do pdVIII. As is the case for pdVIII, thrombin activation of rVIII coagulant activity correlates with the generation of subunits with Mr of 73,000, 50,000 and 43,000. These subunits appear to form a metal-(perhaps Ca2+) linked complex. EDTA inactivates thrombin activated rVIII and pdVIII, with the activity being regenerated after the addition of a molar excess of MnCl2. The results suggest that rVIII is structurally and functionally very similar to pdVIII. PMID- 3102486 TI - Isolation and structure elucidation of an epoxide derivative of the hypermodified nucleoside queuosine from Escherichia coli transfer RNA. AB - A new nucleoside has been identified in tRNATyr from Escherichia coli MRE 600, where it replaces the highly modified nucleoside queuosine. The nucleoside is also present in a large amount relative to queuosine in mixed tRNA from E. coli strains MRE 600 and W (from which it was isolated for characterization). The new nucleoside has been characterized as an epoxy derivative of queuosine: 7-(5-[(2,3 epoxy-4,5-dihydroxycyclopent-1-yl)amino]methyl)-7-de azaguanosine, oQ, based on data from directly combined liquid chromatography/mass spectrometry, high resolution mass spectrometry, and proton NMR spectroscopy. Nucleoside oQ is also present in small amounts in mixed tRNA from E. coli B. Isomerization of oQ occurs readily under alkaline conditions to give a rearranged product, oQ', characterized as 7-(5-[(3,4-epoxy-2,5-dihydroxycyclopent-1-yl)amino]methyl)-7 deaza guanosine. The present finding constitutes the first report of epoxide formation during post-transcriptional processing of RNA. PMID- 3102487 TI - Function of Lys-166 of Rhodospirillum rubrum ribulosebisphosphate carboxylase/oxygenase as examined by site-directed mutagenesis. AB - Affinity labeling and comparative sequence analyses have placed Lys-166 of ribulosebisphosphate carboxylase/oxygenase from Rhodospirillum rubrum at the active site. The unusual nucleophilicity and acidity of the epsilon-amino group of Lys 166 (pKa = 7.9) suggest its involvement in catalysis, perhaps as the base that enolizes ribulosebisphosphate (Hartman, F.C., Milanez, S., and Lee, E.H. (1985) J. Biol. Chem. 260, 13968-13975). In attempts to clarify the role of Lys 166 of the carboxylase, we have used site-directed mutagenesis to replace this lysyl residue with glycine, alanine, serine, glutamine, arginine, cysteine, or histidine. All seven of these mutant proteins, purified by immunoaffinity chromatography, are severely deficient in carboxylase activity; the serine mutant, which is the most active, has a kcat only 0.2% that of the wild-type enzyme. Although low, the carboxylase activity displayed by some of the mutant proteins proves that Lys-166 is not required for substrate binding and argues that the detrimental effects brought about by amino acid substitutions at position 166 do not reflect gross conformational changes. As demonstrated by their ability to tightly bind a transition-state analogue (2-carboxyarabinitol 1,5-bisphosphate) in the presence of CO2 and Mg2+, some of the mutant proteins undergo the carbamylation reaction that is required for activation of the wild type enzyme. Since Lys-166 is required neither for activation (i.e. carbamylation by CO2) nor for substrate binding, it must be essential to catalysis. When viewed within the context of previous related studies, the results of site-directed mutagenesis are entirely consistent with Lys-166 functioning as the base that initiates catalysis by abstracting the C-3 proton from ribulosebisphosphate. An alternative possibility that Lys-166 acts to stabilize a transition state in the reaction pathway cannot be rigorously excluded. PMID- 3102488 TI - Constraints on prostaglandin biosynthesis in tissues. AB - The formation of prostaglandins by prostaglandin H synthase can be limited by the availability of the fatty acid substrate or the hydroperoxide activator and also by a self-catalyzed inactivation associated with the oxygenation reaction. Each pmol of synthase appeared able to form only about 1300 pmol of prostaglandin from arachidonate before it was inactivated. This extent of synthesis was not diminished when substrate fatty acid was complexed with cytosolic proteins even though the velocity of the oxygenation reaction was greatly decreased by the lower availability of substrate acid. When the availability of hydroperoxide activator was decreased by added glutathione peroxidase, the extent of oxygenation per mol of synthase was decreased irrespective of the amount of cytosolic protein present. Approximately 65% of the total prostaglandin synthesis by homogenates was suppressed with a glutathione peroxidase to prostaglandin H synthase ratio of about 90. The remaining prostaglandin synthetic activity was more resistant, being completely suppressed only when the ratio of peroxidase to synthase exceeded 750. The overall ratio of glutathione peroxidase (peroxide removing) capacity to prostaglandin synthetic (peroxide-forming) capacity in selected tissues ranged from over 1800 in rat liver to less than 30 in leukocytes. A comparison between the daily urinary output of prostaglandin metabolites and tissue prostaglandin synthetic capacity suggested that prostaglandin H synthase inactivation along with glutathione peroxidase suppression of the extent of prostaglandin synthase may be important in limiting prostaglandin biosynthesis within cells. PMID- 3102489 TI - Isolation of a rat mitochondrial release factor. Accommodation of the changed genetic code for termination. AB - A single release factor has been isolated and partially purified from rat mitochondria. It requires ethanol in addition to the specific termination codon when assayed in a heterologous system with Escherichia coli ribosomes. The factor recognizes the codons UAA and UAG but not UGA, and therefore it has been designated mtRF-1. A factor of the bacterial RF-2 type, which in E. coli recognizes UGA, or of the mammalian type, which recognizes all three termination codons, has not been detected in mitochondria. The absence of a factor responding to UGA accommodates the use of this codon as a signal for tryptophan in the rat mitochondrial genetic code. The mtRF-1 could translate all of the known termination codons in the rat mitochondrial genome. It does not respond to AGG and AGA which in bovine and human mitochondrial DNA code for termination but which in rat mitochondria may not code for either an amino acid or for termination. PMID- 3102491 TI - Oxidation of human low density lipoprotein results in derivatization of lysine residues of apolipoprotein B by lipid peroxide decomposition products. AB - Modification of low density lipoproteins (LDL) by oxidation has been shown to permit recognition by the acetyl-LDL receptor of macrophages. The extensive oxidation of LDL that is required before interaction occurs with this receptor produces major alterations in both the lipid and protein components of LDL. Several chemical modifications of LDL also lead to recognition by this receptor; all of these involve derivatization of lysine residues of apolipoprotein B by adducts that neutralize the positively charged epsilon-amino group. The present studies show that oxidation also results in derivatization of LDL lysine residues. Analysis of amino acid composition indicated that 32% of lysine residues were modified after oxidation of LDL by exposure to 5 microM CuSO4 for 20 h. About one-half of the derivatized lysines were labile under the conditions of acid hydrolysis. Fluorescence of LDL protein was greatly increased by oxidation, with excitation maximum at 350 nm and emission maximum at 433 nm. When LDL containing phosphatidylcholine with isotopically labeled arachidonic acid in the sn-2 position was oxidized, there was a 5-fold increase in radioactivity bound to protein compared to nonoxidized LDL or oxidized LDL labeled with 2-[1 14C]palmitoyl phosphatidylcholine. Prior methylation of LDL prevented the rapid uptake and degradation by macrophages that normally accompanies oxidation. These findings suggest that oxidation of LDL is accompanied by derivatization of lysine epsilon-amino groups by lipid products and that these adducts may be important in the interaction of oxidized LDL with the acetyl-LDL receptor. PMID- 3102490 TI - Regulation of hormone-sensitive GTP-dependent regulatory proteins by chloride. AB - The activities of GTP-dependent regulatory proteins (G proteins) are modulated by anions. Thus, NaCl stimulated the intensity of the intrinsic tryptophan fluorescence of Go alpha with bound guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) and GTP, but not GDP. This mimics the effect of Mg2+. The salt also increased the affinity of Go alpha for GTP gamma S and GTP, but not GDP, an effect primarily due to decreases in rates of dissociation of the nucleotides. Among the effects of NaCl on the hydrolysis of GTP was an inhibition of the catalytic rate. The modulation of these activities occurred with half-maximal effects in the range of 3-20 mM NaCl. Salts of both chloride and bromide increased the affinity of Go alpha for GTP gamma S; fluoride and iodide were essentially ineffective. Nitrates produced only small and variable effects while SO4(2-) always reduced the affinity. The different cations utilized altered the effect of the anions slightly. The demonstration of direct effects of anions on the alpha subunit of Go suggests that G proteins are one site of action for anion modulation of systems that utilize these proteins. The effects of chloride at modest concentrations suggest potential physiological importance. Chloride may allow activation of G proteins with GTP in the absence of Mg2+ and without subsequent hydrolysis of the nucleotide. PMID- 3102492 TI - An inhibitor of plasminogen activation from human placenta. Purification and characterization. AB - Placental extracts contain inhibitors of human urinary urokinase. These extracts form a heterogeneous population of complexes with 125I-urokinase that are recognizable by changes in gel filtration profile and mobility during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Treatment with reducing agents eliminated the size heterogeneity without loss of activity, thereby allowing the placental inhibitor to be purified. Active inhibitor has been isolated in apparently homogeneous form after an eight-step procedure that included salt extraction, ammonium sulfate fractionation, column chromatography on CM-cellulose, DEAE-Sepharose, and hydroxylapatite, chromatofocusing, preparative gel electrophoresis, and hydrophobic chromatography. The purified inhibitor has Mr = 47,000. The inhibitor is relatively specific for plasminogen activators since it does not inhibit the action of plasmin, factor XIIa, plasma kallikrein, or thrombin. The inhibitor forms complexes with 1:1 stoichiometry that block the active sites of urokinase (but not prourokinase) and both one- and two-chain forms of tissue plasminogen activator. The stability of these complexes in sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggest that they are based on covalently bonded structures. Although both types of plasminogen activator are inhibited, the rate of interaction is significantly faster with urokinase, tissue plasminogen activator being inhibited less efficiently. The complexes formed can be dissociated by mild alkali or hydroxylamine, thereby regenerating both enzymes and inhibitor at their original molecular weights. The results suggest that the complexes are stabilized by ester-like bonds; these might involve the hydroxyl of serine at the active site of the proteases and a carboxyl group in the inhibitor. PMID- 3102493 TI - Atypical glycosylation of an IgG monoclonal cryoimmunoglobulin. AB - The NH2-terminal amino acid sequence of the heavy chain of the IgG monoclonal cryoimmunoglobulin Ger was determined. Evidence for the glycosylation of the first heavy chain hypervariable region of this protein was found. The inability of the deglycosylated Fab fragment of Ger to inhibit cryoprecipitation provides direct evidence that the presence of an additional sialic acid residue in a heavy chain's first hypervariable region can account for the cryo properties of this protein. This is the first convincing description of a molecular defect that explains the atypical low temperature solubility of a monoclonal cryoimmunoglobulin. PMID- 3102494 TI - Allosteric behavior in transducin activation mediated by rhodopsin. Initial rate analysis of guanine nucleotide exchange. AB - Photolyzed rhodopsin acts in a catalytic manner to mediate the exchange of GTP for GDP bound to transducin. We have analyzed the steady-state kinetics of this activation process in order to determine the molecular mechanism of interactions between rhodopsin, transducin, and guanine nucleotides. Initial velocities (Vo) of the exchange reaction catalyzed by rhodopsin were measured for various transducin concentrations at several fixed levels of the GTP analog, [35S]guanosine 5'-(3-O-thio)triphosphate (GTP gamma S). The initial rate data analysis rigorously demonstrates that rhodopsin mediates the activation of transducin by a double-displacement catalytic mechanism. The Michaelis-Menten curves determined as a function of [transducin] reveal remarkable allosteric behavior; analysis of this data yields a Hill coefficient of 2. Lineweaver-Burk plots of Vo-1 versus [transducin]-1 display curvilinearity indicative of positive cooperativity and a series of parallel lines are generated by plotting Vo-1 as a function of [transducin]-2. The plots of Vo-1 versus [GTP gamma S]-1 show no evidence of allosterism and are a parallel series. Furthermore, the allosteric behavior observed in the activation of transducin is also witnessed in the rhodopsin-catalyzed guanine nucleotide exchange of the G protein's purified alpha subunit in the absence of the beta X gamma subunit complex. The latter observation implies that the molecular basis for allosterism in the activation process resides in the interactions between the photoreceptor and transducin's alpha subunit. PMID- 3102495 TI - Biochemical and immunological characterization of rat spleen prostaglandin D synthetase. AB - Rat spleen prostaglandin D synthetase (Christ-Hazelhof, E., and Nugteren, D. H. (1979) Biochim. Biophys. Acta 572, 43-51) is very similar to rat brain prostaglandin D synthetase (Urade, Y., Fujimoto, N., and Hayaishi O. (1985) J. Biol. Chem. 260, 12410-12415) as judged by their pI (4.7-5.2), Mr (26,000 27,000), and self-inactivation during the isomerase reaction from prostaglandin H2 to prostaglandin D2. However, the amino acid compositions of these two enzymes were quite different. Furthermore, the spleen enzyme was associated with the glutathione S-transferase activity, differing from the brain enzyme. The synthetase and transferase activities of the spleen enzyme showed almost identical pH and glutathione dependencies, the optimum pH = 8.0 and Km for glutathione = 300 microM. The Km values for prostaglandin H2 and 1-chloro-2,4 dinitrobenzene (a substrate for the transferase) were about 200 microM and 5 mM, respectively. The synthetase activity was dose-dependently inhibited by 1-chloro 2,4-dinitrobenzene (IC50: approximately 5 mM) and more strongly by nonsubstrate ligands, such as bilirubin and indocyanine green (IC50: 150 and 2 microM, respectively). Both the synthetase and transferase activities of the purified enzyme dose-dependently decreased and showed identical immunotitration curves by incubation with antibody against this enzyme, but remained unchanged when treated with antibody against the brain enzyme. The antibody specific for the spleen enzyme absorbed almost all of the synthetase activity and about 10% of the transferase activity in the spleen, but not the transferase activity in the liver, heart, and testis. These results show that the two types of prostaglandin D synthetase are similar but different enzymes and that the spleen enzyme is a unique glutathione S-transferase differing from other isozymes and their subunits reported previously. PMID- 3102496 TI - The standardisation of gauge length: its influence on the relative extensibility of natural and chemically modified pericardium. AB - Cyclic uniaxial load tests were performed on natural and chemically modified bovine pericardium which is used in the construction of heart valve substitutes. A template was employed to select specimens from the same sites in different pericardial sacs. When the pericardium was chemically modified by glutaraldehyde fixation as an entire sac the tissue showed increased extensibility after modification compared with the natural tissue. The undeformed stress-free length (gauge length) in both the natural and modified tissue was determined by a highly reproducible experimental method giving a coefficient of variation of less than 0.5%. Specimens excised from a natural pericardial sac demonstrated a significant increase (p less than 0.03) in length, 4.97 +/- 3.49%, after a single load cycle, compared with controls placed in isotonic saline but not mechanically tested. The test pieces had returned to their original length by 8.5 h after the mechanical test. After fixation the same specimens decreased significantly in length (p less than 0.001) by 11.18 +/- 4.28%. This shrinkage was not significantly different to that of the control specimens (11.09 +/- 2.47%) which had not been tested. Uniaxial loading of these chemically modified strips demonstrated a similar increase in tissue extensibility compared to the natural tissue if the undeformed length of the test specimen after shrinkage was used as the gauge length. After mechanical conditioning the chemically modified tissue also demonstrated a significant increase (p less than 0.001) in stress-free length (5.35 +/- 0.59% after 36 cycles, 8.92 +/- 1.50% after 2085 cycles). These deformations were not permanent. The tissue had returned to its original length after 38 h in its normal buffered glutaraldehyde storage medium. On the basis of these observations, recommendations for the clarification and standardisation of gauge length definitions were made in natural, chemically modified and mechanically conditioned tissue. PMID- 3102497 TI - The relationship between oblique fractures of the medial malleolus and concomitant fractures of the anterolateral aspect of the tibial plafond. AB - Considerable disagreement exists concerning the mechanism by which the relatively uncommon oblique fracture of the medial malleolus is produced, and to our knowledge the relationship between it and a fracture of the anterolateral aspect of the tibial plafond has not previously been recognized. We treated a patient with these fractures whose deformed steel-reinforced work boot indicated that the mechanism of injury had been external rotation, dorsiflexion, and abduction. We found this fracture pattern in eleven other patients. We concluded that the malleolar fracture is an oblique avulsion injury and that impingement of the talus on the anterolateral aspect of the tibial plafond accounts for the other fracture. The identification of an oblique medial malleolar fracture should prompt a search for a fracture of the anterolateral aspect of the tibial plafond; the reverse is also true. PMID- 3102498 TI - The Elephant Woman. Neurofibromatosis associated with pseudarthrosis of the humerus. AB - A woman with neurofibromatosis (von Recklinghausen's disease) presented with a giant plexiform neuroma of the arm and chest wall, with dysplastic scoliosis and a pseudarthrosis of the humerus. Her arm resembled that of the "Elephant Man" described by Sir Frederick Treves. PMID- 3102499 TI - Unrecognised compartment syndrome in a patient with tourniquet palsy. AB - We report a case in which compartment syndrome and tourniquet paralysis occurred simultaneously. This is a previously unreported combination which presents a diagnostic problem. We recommend that electrophysiological studies and continuous monitoring of compartment pressures should be used to minimise morbidity in high risk cases. PMID- 3102500 TI - Symptomatic ossicles of the lateral malleolus in children. AB - We describe three children with symptoms of damage to the attachment of an anomalous ossific centre of the lower fibular epiphysis. All three were aged 8 to 10 years at the time of the initial injury, had suffered recurrent ankle sprains and had well localised and consistent tenderness precisely at the site of the anomalous ossific centre. All their symptoms were relieved by excision of the ossicle with reconstitution of the fibular collateral ligament. Whilst a separate secondary centre of ossification at the lower fibula is present in 1% of healthy children between the ages of 6 and 12 years, the condition described is extremely uncommon. Excision of the fragment should be reserved for those patients with recalcitrant symptoms and with consistent tenderness precisely at the site of the accessory ossicle. PMID- 3102501 TI - Relationship between clinical parameters and pharmacokinetics of mitomycin C. AB - Although the number of reports on mitomycin C (MMC) pharmacokinetics is increasing, data on possible relations between clinical parameters and pharmacokinetics are usually lacking. The present report concerns the results of a detailed study on this subject in 35 patients receiving MMC, either as a single agent or as a part of combination chemotherapy. MMC concentrations were determined by HPLC. T1/2 beta varied from 23 to 78 min, VD from 11 to 48 l/m2, Cl tot from 12 to 42 l/h per m2, and AUC from 138 to 1221 micrograms/h per l, confirming previously reported data. Infusion time, cholestasis, and urinary pH did not influence the pharmacokinetic data. There were no relations between other clinical data and pharmacokinetics, nor between AUC and bone marrow toxicity. An interaction between MMC and furosemide could not be excluded, but there was no interaction with other comedication. Consecutive pharmacokinetics in 6 patients showed consistent results. Because renal impairment does not alter MMC pharmacokinetics and renal excretion is not a major route of elimination, it is suggested that renal impairment does not call for dose adjustment. PMID- 3102502 TI - Properties of smooth muscle meta-vinculin. AB - Quantitative studies show that meta-vinculin is ninefold more soluble in 0.6 M salt than in the 0.01 M salt buffers used to extract vinculin. Based on this finding, we have developed a protocol for the purification of meta-vinculin in 43% yield and 98% purity from a high salt extract of gizzard smooth muscle. In contrast to our earlier extraction studies, which were done on unfixed cryostat sections (30), the present studies done on tissue homogenates show that nonionic detergents are not required for solubilization of meta-vinculin. Furthermore, neither purified nor partially purified meta-vinculin binds to Triton X-114 micelles. Purified meta-vinculin is a monomeric, asymmetric molecule with a Stokes radius of 50.9 A, a sedimentation coefficient of 6.35S, and a frictional ratio of 1.46. The calculated molecular weight of meta-vinculin is 145,000. Meta vinculin has two isoforms of pI 5.9 and 6.2, and is phosphorylated in vivo to eightfold greater specific activity than vinculin. On immunoblots of smooth muscle proteins, [125I]meta-vinculin binds specifically to talin and also to unidentified polypeptides of 180, 150, 95, 70, 68, and 45 kD. On two-dimensional peptide maps, iodinated vinculin and meta-vinculin have at least 95% of their major chymotryptic peptides in common, but each protein also has at least one highly labeled peptide that appears to be unique. Comparative peptide maps of high salt soluble meta-vinculin and the low salt soluble 152-kD protein (described by Feramisco, J.R., J.E. Smart, K. Burridge, D. Helfman, and G.P. Thomas, 1982, J. Biol. Chem., 257:11024-11031) demonstrate extensive similarities among the vinculin-like proteins but suggest a lack of complete identity. In vivo pulse-chase experiments show that meta-vinculin and vinculin do not have a precursor-product relationship. The biochemical and structural differences found between vinculin and meta-vinculin suggest that there is a unique function for meta-vinculin in smooth muscle. PMID- 3102503 TI - Inhibition of endothelial cell proliferation by gamma-interferon. AB - Endothelial cell growth factor (ECGF) is a potent polypeptide mitogen for endothelial cells and fibroblasts. The mitogenic effects of ECGF are inhibited by the lymphokine gamma-interferon (gamma-IFN) in a dose-dependent manner. Gamma-IFN also induces a unique change in endothelial cell morphology which is maximally expressed in the presence of ECGF. The antiproliferative and phenotypic modulatory effects of gamma-IFN on endothelial cells are reversible. Inhibition of ECGF-induced endothelial cell proliferation by gamma-IFN is accompanied by a concentration- and time-dependent decrease in binding of 125I-ECGF to the endothelial cell surface. Scatchard analyses of the binding data in the presence and absence of gamma-IFN demonstrate a decrease in the number of ECGF-binding sites rather than a decrease in ligand affinity for the receptor. Cross-linking experiments with disuccinimidyl suberate demonstrate a decrease in the 170,000 Mr cross-linked receptor-ligand complex. These data suggest that gamma-IFN inhibits endothelial cell proliferation by a mechanism which involves growth factor receptor modulation. PMID- 3102504 TI - Phorbol ester induces the biosynthesis of glycosylated and nonglycosylated plasminogen activator inhibitor 2 in high excess over urokinase-type plasminogen activator in human U-937 lymphoma cells. AB - The tumor-promoting phorbol ester PMA induces changes in the histiocytic human lymphoma cell line U-937 akin to cellular differentiation (Ralph, P., N. Williams, M. A. S. Moore, and P. B. Litcofsky, 1982, Cell. Immunol., 71:215-223) and concomitantly stimulates the biosynthesis of plasminogen activator inhibitor 2 (PAI 2) and of urokinase-type plasminogen activator (u-PA). PAI 2 is found in a nonglycosylated intracellular and a glycosylated secreted form. The former appears to be identical to PAI 2 previously purified from placental extracts and large-scale U-937 cell cultures. The sixfold increase of PAI 2 antigen measured 24 h after PMA treatment in cell extracts and conditioned media is accompanied by an equal increase of active PAI 2 mRNA, whereas the 6 to 13-fold increase of u-PA antigen in the same samples is associated with only a 1.5-fold mRNA increase. The increase of PAI 2, but not of u-PA, biosynthesis requires transcription. A 50 fold molar excess of PAI 2 over u-PA is found in both extracts and conditioned media of PMA-treated cells. PAI 2 represents at least 0.3% of total de novo synthesized protein 24 h after induction with PMA. Thus, PAI 2, but not u-PA, is an abundant product of this precursor analogue of the mononuclear phagocyte lineage, and might represent a new marker for monocyte/macrophage differentiation. PMID- 3102505 TI - Assembly and secretion of heavy chains that do not associate posttranslationally with immunoglobulin heavy chain-binding protein. AB - Heavy chain-binding protein (BiP) associates posttranslationally with nascent Ig heavy chains in the endoplasmic reticulum (ER) and remains associated with these heavy chains until they assemble with light chains. The heavy chain-BiP complex can be precipitated by antibody reagents against either component. To identify sites on heavy chain molecules that are important for association with BiP, we have examined 30 mouse myelomas and hybridomas that synthesize Ig heavy chains with well characterized deletions. Mutant Ig heavy chains that lack the CH1 domain could not be demonstrated to associate with BiP, whereas mutant Ig heavy chains with deletions of the CH2 or CH3 domain were still able to associate with BiP. In two light chain negative cell lines that produced heavy chains with deletions of the CH1 domain, free heavy chains were secreted. When Ig assembly and secretion were examined in mutants that did not associate with BiP, and were compared with normal parental lines, it was found that the rate of Ig secretion was increased in the mutant lines and that the Ig molecules were secreted in various stages of assembly. In one mutant line (CH1-) approximately one-third of the secreted Ig molecules were incompletely assembled, whereas the Ig molecules secreted by the parental line were completely assembled. Our data show the CH1 domain to be important for association with BiP and that when this association does not occur, incompletely assembled heavy chains can be secreted. This implies a role for BiP in preventing the transport of unassembled Ig molecules from the ER. PMID- 3102507 TI - Induction of major histocompatibility class I antigens by interferons in undifferentiated F9 cells. AB - Mouse embryonal carcinoma F9 cells, upon treatment with interferons (IFNs), express major histocompatibility (MHC) Class I antigens, which are otherwise not expressed in these cells. Both IFN-gamma and IFN-alpha/beta increase the steady state level of Class I mRNA within 60 min of the treatment which leads to the subsequent surface expression of the H-2Kb and H-2Db antigens, suggesting that undifferentiated F9 cells express IFN receptors. IFNs induce Class I antigen expression in F9 cells in a highly selective manner: unlike retinoic acid treatment which also stimulates the antigen expression, IFNs induce neither morphological differentiation, increased binding of epidermal growth factor, nor reduction of expression of stage specific embryonic antigen. The effect of IFNs is reversible; removal of IFNs, even after prolonged exposures, results in a rapid loss of the Class I gene expression. Further, Class I mRNA induction is not inhibited by cycloheximide, suggesting possible independence from de novo protein synthesis. This Class I antigen induction in F9 cells is reminiscent of that observed in somite stage mouse embryos by IFN treatment and may offer a model system to study activation of MHC genes during development. PMID- 3102506 TI - Inhibition of fibroblast chemotaxis by recombinant human interferon gamma and interferon alpha. AB - Interferons have recently been recognized as potent mediators in inflammatory processes, exerting profound effects on fibroblasts. The influence of interferons gamma and alpha on the chemotactic movement of fibroblasts toward various attractants was, therefore, investigated. Normal human adult and embryonal dermal fibroblasts, fibrosarcoma-derived fibroblasts and SV40-transformed fibroblasts were tested against conditioned medium from fibroblasts, the chemotactic peptide C-140 of fibronectin, platelet-derived growth factor, and leukotriene B4 as attractants in the presence or absence of the interferons. Interferons gamma and alpha inhibited chemotaxis in a dose-dependent manner and at concentrations at least as low as 10(-2) ng/ml. Inhibition was noticeable when the cells were exposed to interferon for as short a period as 60 minutes, and the effect was not readily reversible. Inhibition occurred when the cells came from sparse or dense cultures, but when platelet-derived growth factor was the attractant and the cells had been grown at low density there was no inhibition. It is concluded that this is a specific effect, not to be wholly explained by overall increase in membrane rigidity. Inhibition of fibroblast chemotaxis by interferons may be an important regulatory mechanism during wound healing or fibrosis and metastatic spread of tumor cells. PMID- 3102508 TI - An alcoholic woman with acute abdominal pain. PMID- 3102509 TI - Management of transient ischemic attacks. PMID- 3102510 TI - Carcinoma of the pancreas. PMID- 3102511 TI - Diagnosis and treatment of otalgia. PMID- 3102512 TI - Polycythemia vera, diagnosis and treatment. PMID- 3102513 TI - Myocardial deterioration in a young mother. PMID- 3102514 TI - Two misdiagnoses of disturbed ex-soldier. PMID- 3102515 TI - Cough and spiking fever in a transfusion-dependent woman. PMID- 3102516 TI - It's what you believe that counts. PMID- 3102517 TI - A hemophiliac man with an oozing flank mass. PMID- 3102519 TI - P450 genes and evolutionary genetics. PMID- 3102518 TI - Complex arrhythmia in a comatose patient. PMID- 3102520 TI - Gonadal failure in a short teenage girl. PMID- 3102521 TI - Defense of euglycemia: failure in insulin-dependent diabetes. PMID- 3102522 TI - Treatment modalities in Guillain-Barre syndrome. PMID- 3102524 TI - Of peas, fruit flies, and the birth of a science. PMID- 3102523 TI - Epigastric pain and spiking liver enzymes. PMID- 3102525 TI - Stupor, stiff neck, and fever after closed-head injury. PMID- 3102526 TI - Asymptomatic tachycardia. PMID- 3102527 TI - The elderly patient with cataract. PMID- 3102528 TI - Mitral valve prolapse. The unresolved questions. PMID- 3102529 TI - Evaluation of the neck veins. AB - In spite of numerous technical advances in cardiovascular diagnosis, the bases for determination of the need for diagnostic tests and therapy and for evaluation of the response to therapy often remain the history and bedside physical findings. The complete cardiovascular examination includes evaluation of the arterial pulsations, the precordial pulsations, and cardiac auscultation. The correct interpretation of the jugular venous pulse is an integral part of the examination. The jugular venous pulsations reflect the systolic and diastolic hemodynamics of the right atrium and, in the absence of obstruction of the tricuspid valve, of the right ventricle as well. When correctly interpreted, the jugular venous pulsations provide information about right ventricular hemodynamics and important clues to the diagnosis. Instead of trying to find the classically described A and V waves in normal people, one should look for the systolic collapse of the normal jugular venous pulse. When one is thoroughly familiar with the normal variations, the few common abnormalities are easy to appreciate. PMID- 3102531 TI - Who is a good clinician? PMID- 3102530 TI - Young woman on a prednisone seesaw. PMID- 3102533 TI - Purification of human leucocyte pyruvate kinase. AB - The M2 form of pyruvate kinase (M2-PK) was purified from human leucocytes by a new method involving a succession of two different Dyematrex agarose chromatographies. The main step consisted of an orange dye affinity column with elution by fructose-1,6-diphosphate. This purification procedure allowed us to obtain M2-PK with a specific activity of 433 I.U./mg of protein, i.e. a 188-fold purification with an overall yield of 33%. The homogeneity of this preparation was verified by sodium dodecyl sulphate polyacrylamide gel electrophoresis and double immunodiffusion in Ouchterlony plates. Anti-M2-PK antibodies obtained from rabbit neutralized the enzyme activity. Their specificity with regard to other types of PK showed that anti-M2-PK also reacted with M1-PK but not with R-PK. PMID- 3102532 TI - Medical aspects of contraception. AB - It is evident that choice of contraceptive has important medical implications, whether a mechanical or a hormonal method is elected. Each technology has unique benefits and risks, constraints, applicability, and inconvenience. Wise advice in a medical context must be based on thorough familiarity with the options available to each woman. PMID- 3102534 TI - Liquid chromatographic assay for the measurement of glucuronidation of arylcarboxylic acids using uridine diphospho-[U-14C] glucuronic acid. AB - A general method for the assay of UDP-glucuronosyltransferase activity towards arylcarboxylic acids (clofibric acid, 1- and 2-naphthylacetic acid) using UDP-[U 14C] glucuronic acid in liver microsomes is described. The 14C-labelled glucuronide was separated by high-performance liquid chromatography, identified by hydrolysis by beta-glucuronidase, characterized by laser desorption mass spectrometry and quantified by scintillation counting. The coefficient of variation of the enzyme activity for the inter-assay repeatability was below 4.5%. As little as 2.5 nmol of the arylcarboxylic acid glucuronides could be detected and precisely quantified. The method was applied to the determination of the apparent kinetic constants for glucuronidation of the acids. Clofibric acid was the best substrate for UDP-glucuronosyltransferase (Vmax/KM, the ratio of the maximum initial velocity and the Michaelis-Menten constant, is 12.3). The two isomers, 1- and 2-naphthylacetic acids, were transformed at a similar rate. However, they exhibited different enzymatic affinities, as the KM values were 1.0 mM and 5.6 mM for 1- and 2-naphthylacetic acid, respectively. This indicates that the spatial organization of the substrates played a critical role in this acyl glucuronoconjugation. PMID- 3102535 TI - High-performance liquid chromatographic determination of glibenclamide in human plasma and urine. AB - A selective and sensitive high-performance liquid chromatographic method for determination of intact glibenclamide in human plasma or urine has been developed. With glibornuride as internal standard, acid-buffered plasma or urine was extracted with benzene. The organic layer was evaporated and the residue was dissolved in equilibrated mobile phase (acetonitrile-phosphate buffer 0.01 M pH 3.5, 50:50). An aliquot of 20 microliters was chromatographed on a Spherisorb ODS reversed-phase column, and quantitation was achieved by monitoring the ultraviolet absorbance at 225 nm. The response was linear (0-1000 ng/ml) and the detection limit was 5-10 ng/ml in plasma or urine. The within-assay variation was less than or equal to 10%. No interferences from metabolites or endogenous constituents could be noted. The utility of the method was demonstrated by analysing glibenclamide in samples from diabetic subjects on therapeutic doses of the drug. PMID- 3102536 TI - Assessment of sensitive thyrotropin assays for an expanded role in thyroid function testing: proposed criteria for analytic performance and clinical utility. AB - Assays capable of detecting subnormal serum TSH concentrations can permit the prediction of response to TRH and the detection of hyperthyroidism. Five performance criteria for evaluating the eligibility of TSH assays for these new roles are proposed. Criterion 1 requires a less than 1% overlap between the variation of the lower normal value and the assay detection limit. Criteria 2 and 3 require subnormal basal TSH values in 95% of patients with subnormal TRH response, and detectable basal TSH values in 95% of patients with normal TRH responses. Criteria 4 and 5 require undetectable TSH values in 95% of hyperthyroid patients and detectable TSH values in 95% of clinically euthyroid subjects. Evaluation of 20 published studies using commercial reagents showed that only 5 assays met criterion 1; most reports did not provide adequate information for evaluation. We evaluated 2 sensitive assays by assessment of sera from 149 normal subjects and 893 patients. Substantial differences were found; only assay B met all performance criteria. With assay B, serum TSH levels were normal in 86%, increased in 7%, undetectable in 4%, and subnormal in 3% of 454 patients undergoing a screening T4 measurement. Sensitive TSH assays fulfilling our criteria may be useful as front-line thyroid function tests. PMID- 3102537 TI - Monitoring the menstrual cycle of humans and lowland gorillas based on urinary profiles of bioactive follicle-stimulating hormone and steroid metabolites. AB - A sensitive and specific in vitro granulosa cell aromatase bioassay was adapted to measure bioactive FSH (bio-FSH) levels in urine samples. Urinary levels of bio FSH, immunoreactive LH, estrone conjugates, and pregnanediol-3-glucuronide (PdG) were measured in first morning urine samples during the menstrual cycle in six cycling women and four lowland gorillas. The cycle length of women was relatively constant [28 +/- 1 (+/- SD) days], but varied from 28-38 days for lowland gorillas; the length of the luteal phases was relatively constant for both. All subjects had a midcycle LH peak and a luteal phase elevation in PdG. In addition, urinary estrogen excretion displayed a midcycle elevation that preceded the LH peak and a luteal phase increase similar to that of PdG. The bio-FSH levels in urine of cycling women, although at almost 100-fold higher concentrations, exhibited a pattern that closely resembled that of serum bio-FSH levels reported earlier, with an early follicular phase rise and a midcycle peak. Statistical analysis indicated a highly significant correlation (r = 0.90) between serum and urinary bio-FSH levels during the human menstrual cycle and in women in several hypo- and hypergonadotropic states, including oral contraceptive pill users, hypothalamic amenorrhea, premature ovarian failure, and postmenopause. Although a midcycle bio-FSH surge was also detected in lowland gorillas, two peaks of bio FSH levels were consistently found during the follicular phase. The late follicular phase increase in bio-FSH levels was presumably involved in follicle selection and preceded the midcycle FSH peak by about 6 days, whereas the timing of the early follicular phase peak was variable, suggesting the involvement of complex regulatory mechanisms. These findings suggest that measurement of urinary bio-FSH levels in humans reflects serum bio-FSH in subjects in several physiological and pathological states. Studies of urinary bio-FSH levels in humans and nonhuman primates are useful in monitoring menstrual cycles, and the gorillas may be a model for understanding human reproductive cycles. The urinary granulosa cell aromatase bioassay should be useful for future assessment of bio FSH levels in situations where serum measurements are impractical or in animal species for which specific FSH RIAs are not available. PMID- 3102538 TI - Free estradiol, free testosterone, and sex hormone-binding globulin in perimenopausal women. AB - To determine whether menstrual status had an effect on plasma sex hormone-binding globulin (SHBG) capacity and nonprotein-bound estradiol (% free E2) and testosterone (% free T), we measured these as well as plasma FSH, total E2, and T and the MCRs of E2 and T in a group of 78 perimenopausal women. The women were allocated to 4 groups: women with cycles whose plasma FSH level was less than 40 mIU/mL (A; n = 16), women with cycles whose plasma FSH level was greater than 40 mIU/mL (B; n = 19), women who were amenorrheic for less than 1 yr (C; n = 13), and women who were amenorrheic for more than 1 yr (D; n = 30). The mean plasma SHBG values were 51.4 +/- 5.7 (+/- SE), 48.3 +/- 4.3, 45.9 +/- 5.4, and 51.1 +/- 3.7 nM in groups 1-4 respectively, and were not significantly different from one another. The mean % free E2 and % free T values also were not different between the groups. However, the mean total E2 and free E2 (% free E2 X E2/100) concentrations were significantly (P less than 0.05) higher in both groups A and B than in groups C and D. The E2 concentration was also higher in group A than in group B. There were strong correlations between the E2 and free E2 concentrations between the T and free T (% free T X T/100); (P less than 0.0001) concentrations, between SHBG capacity and weight, and between the MCRs of both E2 and T and % free E2 and % free T. In normal women, the menopause is not associated with changes in SHBG or % free steroids. Hence, the measurement of E2 could be used to predict the mass of free E2 in these women. PMID- 3102539 TI - Oral contraception and insulin sensitivity: in vivo assessment in normal women and women with previous gestational diabetes. AB - The sensitivity to insulin (euglycemic clamp technique) was assessed in previous gestational diabetic women (n = 6) and nondiabetic women (n = 6) before and twice during low-dose triphasic oral contraceptive administration (ethinyl estradiol and levonorgestrel) for 6 months. Both groups had normal plasma glucose and insulin levels during oral glucose tolerance tests before and during treatment. In vivo peripheral insulin action was measured during insulin infusion of 40 mU/m2 X min with plasma glucose clamped at fasting levels. Before treatment glucose infusion rates were identical in both groups [1.56 +/- 0.12 (SEM) mmol/m2 X min and 1.51 +/- 0.09 mmol/m2 X min, respectively]. After hormonal treatment for 6 months the amount of glucose infused decreased significantly in the previously gestational diabetic women (1.10 +/- 0.12 mmol/m2 X min, P = 0.01), whereas the decrease was less pronounced in the nondiabetic women (1.30 +/- 0.22 mmol/m2 X min, P = 0.09). The decrease in insulin sensitivity was not sufficient to alter glucose tolerance either in the previous gestational diabetic women nor in the nondiabetic women. PMID- 3102540 TI - The effects of bromocriptine, thyrotropin-releasing hormone, and gonadotropin releasing hormone on hormone secretion by gonadotropin-secreting pituitary adenomas in vivo and in vitro. AB - The characteristics and dynamics of hormone secretion in vivo and in vitro were investigated in six patients with gonadotropin-secreting pituitary adenomas. All six tumors secreted and contained FSH and different combinations of LH, beta-LH, and alpha-subunit. In addition, immunohistochemical examination of the pituitary tumor tissue showed staining with both LH and FSH in three and either LH or FSH in the other three tumors. TRH and GnRH stimulated hormone secretion in vivo and in vitro, and they also increased the hormone content of the cultured tumor cells. Bromocriptine significantly inhibited hormone release and reduced the hormone content of the tumor cells. In vivo, 2.5 mg bromocriptine significantly suppressed plasma hormone levels; the inhibiting effect on alpha-subunit concentrations was in general more marked than that on LH and FSH. We conclude that hormone release by gonadotropin-secreting pituitary adenomas can be stimulated by TRH and GnRH and inhibited by bromocriptine. Most of these tumors synthesize FSH, but there is a wide variation in the production of LH, beta-LH, and alpha-subunits. The sensitivity of hormone release to bromocriptine suggests that chronic therapy with this drug might have a beneficial effect on pituitary tumor size. PMID- 3102541 TI - Luteinizing hormone-secreting pituitary tumor: biosynthetic characterization and clinical studies. AB - Although gonadotropin-secreting pituitary adenomas are increasingly recognized, tumors secreting only LH are rare. Since gonadotropin production by pituitary adenomas may reflect imbalanced glycoprotein biosynthesis, we studied tumor LH and subunit biosynthesis and secretion in a patient with a LH- and alpha-subunit producing pituitary tumor. Northern blot analysis of RNA from the tumor revealed the presence of mRNAs encoding both alpha- and beta-subunits of LH with a marked excess of the mRNA encoding LH beta. Analysis of tumor extracts by gel filtration chromatography confirmed an excess of free LH beta relative to free alpha subunit. Clinical studies demonstrated that the secretion of LH and alpha-subunit by the tumor increased in response to the acute administration of LHRH (100 micrograms, iv) and decreased during a 4-h dopamine infusion (4 micrograms/kg X min). During a 4-week course of LHRH analog (D-Trp6-Pro9-NEt-LHRH) administration, given as a daily sc dose (8 micrograms/kg X day), serum LH and alpha-subunit concentrations increased 7- and 3-fold, respectively, consistent with a chronic agonist effect. Chronic administration of bromocriptine resulted in reduction of serum LH and alpha-subunit levels to normal. PMID- 3102542 TI - Lymphokine regulation of HLA-DR gene expression in human thyroid cell monolayers. AB - Studies were conducted to examine the regulation of HLA class II gene expression in human thyroid cells in vitro. Normal human thyroid cells cultured in the absence of lectin or gamma-interferon stimulation lacked detectable HLA-DR cell surface antigen, although low levels of DR alpha-chain-specific mRNA were present. Cyclosporine A, known to inhibit lymphokine production, inhibited basal as well as lectin-mediated increases in levels of DR alpha-chain-specific mRNA and DR surface antigen expression on normal human thyrocytes. Cyclosporine had no effect on the induction of DR antigen gene expression by recombinant gamma interferon. These data suggested that lectin enhancement of DR antigen expression in human thyroid cells may be mediated by a lymphokine(s) produced in primary human thyroid cell monolayers. This suggestion was confirmed by studies that demonstrated the abrogation of lectin responsiveness by antibody directed against gamma-interferon. Indirect immunofluorescence studies using flow cytometric analyses identified 1.6 +/- 0.2% (mean +/- SD) of cells in primary thyroid cultures as T lymphocytes, a potential source of lymphokine production. Cells derived from thyroid follicular adenomas and carcinomas demonstrated reduced lectin-mediated increases in DR antigen expression compared to normal thyroid cells. DR expression could be enhanced in these lectin-treated cells, however, by T cell coculture. Dose-response studies demonstrated that human thyroid cells were as sensitive to gamma-interferon induction of DR antigen expression as human monocyte/macrophages. These results indicate that human thyroid cell HLA-DR antigen gene expression is sensitive to low levels of lymphokines, such as gamma interferon; an intrathyroidal T cell population, which may serve as a source of lymphokine(s), remains associated with thyroid epithelial cells in primary thyroid cultures; and lymphokine-thyroid cell interactions may be implicated in the immunopathology of human autoimmune thyroid disease. PMID- 3102543 TI - Lack of desensitization of adenomatous somatotrophs to growth-hormone releasing hormone in acromegaly. AB - The study was undertaken to investigate whether GHRH causes desensitization in GH secreting adenomas in analogy to the normal situation. For this purpose, GH secretion after repeated GHRH administration to acromegalic patients in vivo and cultured adenomatous somatotrophs in vitro was studied. Six acromegalic patients and 6 normal subjects received 3 consecutive 50 micrograms GHRH rapid iv injections at 2-h intervals. Blood samples were drawn at 0, 15, 30, 60, and 120 min after each dose. The acromegalic patients had variable responses to the first injection and in each patient the second and third injections elicited serum GH responses that were quite similar to those after the first one. The GH increment, evaluated as net incremental area under the curve (mean +/- SE; nanograms per ml/120 min) was 2660 +/- 1501 after the first injection, 2176 +/- 1378 after the second injection, and 1978 +/- 1191 after the third injection; P = NS. On the contrary, in normal subjects a marked elevation of GH was observed only after the first injection (net incremental area under the curve, mean +/- SE after the first injection: 710 +/- 154; after the second injection: 6 +/- 39 and after the third injection: 108 +/- 28, P less than 0.01 vs. the first dose). The effect of in vitro GHRH pretreatment on the subsequent response to GHRH was evaluated in monlayer cultures from 12 GH-secreting adenomas. At 10(-8) M, GHRH significantly stimulated GH release from 8 adenomas. The GHRH pretreatment that was effective in inducing desensitization in cultured rat anterior pituitary cells, i.e. preexposure of the cultured cells to 10(-8) M GHRH for 4 h at 37 C, did not abolish the GH response to the subsequent challenge with GHRH (mean percent stimulation: 150 +/- 14% in untreated cells vs. 153 +/- 30% in pretreated cells; P = NS). Only in one adenoma, did GHRH-promoted desensitization occur. No modification was found in GHRH unresponsive adenomas. In the adenomas, not only the efficacy but also the potency of GHRH on GH release after GHRH pretreatment was of the same order of magnitude as in untreated cells. No desensitization to GHRH action occurred when the pretreatment time was prolonged up to 8 h and the GHRH concentration in the preincubation medium was increased to 10(-7) M.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3102544 TI - Ultradian oscillations of plasma glucose, insulin, and C-peptide in man during continuous enteral nutrition. AB - The profiles of plasma glucose, insulin, and C-peptide were studied in normal men receiving continuous enteral nutrition. Large oscillations occurred with periods of 53-113 min. Their mean amplitudes, expressed as a percentage of the 24-h mean, were as high as 20% for glucose, 54% for insulin, and 56% for C-peptide. The oscillations of plasma insulin levels throughout the 24 h were concomitant with those of C-peptide. Rapid 8- to 14-min plasma insulin and glucose oscillations were smaller in magnitude and could only be detected in some segments of the longer period oscillations. These results indicate that in addition to the previously described 8- to 14-min oscillations, plasma glucose, insulin, and C peptide oscillate at a mean 80-min periodicity in man during continuous enteral nutrition. These oscillations may reflect a pancreatic oscillatory mechanism and/or cyclic variations in gastrointestinal motility or peripheral glucose uptake. PMID- 3102545 TI - Differential control of luteinizing hormone and follicle-stimulating hormone secretion by luteinizing hormone-releasing hormone pulse frequency in man. AB - To test the hypothesis that the frequency of pulsatile LHRH stimulation can differentially control LH and FSH secretion in man, we administered low doses of LHRH in pulsatile fashion in several different regimens to men with idiopathic hypogonadotropic hypogonadism (IHH) and presumed endogenous LHRH deficiency. In study 1, four men with IHH received a constant amount of LHRH per day in three different frequencies. After an initial 7-day period of LHRH (5.0 micrograms every 2 h), the men received 2.5 micrograms every 1 h and 7.5 micrograms every 3 h, each for 4 days, in varying order. Frequent blood samples were obtained before LHRH administration and at the end of each regimen. Before LHRH administration, mean serum FSH and LH levels were low [28 +/- 3 (+/- SEM) and 6 +/- 2 ng/mL, respectively], and they increased into the normal adult male range during LHRH treatment. As the frequency of LHRH administration decreased from every 1 to 2 to 3 h, serum FSH levels progressively increased from 99 +/- 33 to 133 +/- 34 to 181 +/- 58 ng/mL (P less than 0.05). Serum LH levels (34 +/- 6, 33 +/- 6, and 34 +/- 5 ng/mL) were significantly higher than those before LHRH administration and did not differ significantly among the three regimens. Total serum testosterone (T), estradiol, and free T levels were increased by LHRH, but were not significantly different during the three regions of LHRH administration. In study 2, three men with IHH received the same amount of LHRH per dose, given in two different pulse frequencies; 2.5 micrograms LHRH were administered in frequencies of every 0.5 h and every 1.5 h, each for 4 days, in varying order. During the 0.5 h frequency, the mean serum FSH level was 42 +/- 13 ng/mL, and it rose to 80 +/- 19 ng/mL during the 1.5 h frequency (P less than 0.05). Corresponding mean serum LH levels were 25 +/- 5 and 27 +/- 4 ng/mL. Serum T and estradiol levels were not significantly different during the two LHRH regimens. We conclude that the frequency of LHRH stimulation can differentially control FSH and LH secretion by the human pituitary gland, and the pattern of hormonal stimulation may be a determinant of target organ response. PMID- 3102546 TI - Sex steroids and pulsatile luteinizing hormone release in men. Studies in estrogen-treated agonadal subjects and eugonadal subjects treated with a novel nonsteroidal antiandrogen. AB - This study evaluated the effects of estrogens and androgens on LH pulse frequency and amplitude in male subjects. To assess the role of estrogens we compared the serum LH pulse frequency and amplitude between 3 groups: 8 agonadal subjects receiving no steroid treatment; 6 agonadal subjects continuously treated with 50 micrograms ethinylestradiol/day; and 17 eugonadal men. Mean serum LH levels and LH pulse amplitude were significantly lower in the agonadal subjects receiving estrogens (14.8 +/- 5.4 (SD) U/L and 4.1 +/- 1.5 U/L, respectively) than in the group of agonadal subjects not receiving sex steroid treatment (35.7 +/- 8.4 U/L and 7.3 +/- 2.0 U/L, respectively). The mean LH pulse frequency was 7.1 +/- 1.5/7 h in the group not receiving sex steroid treatment and 6.0 +/- 1.4/7 h in the group receiving estrogens (P NS). The LH pulse frequency in the eugonadal men (3.8 +/- 1.3/7 h) was significantly lower than the frequency in both groups of agonadal subjects. The LH pulse amplitude was of the same magnitude in the estrogen-treated agonadal subjects and in eugonadal men (4.1 +/- 1.5 U/L and 3.5 +/- 1.2 U/L, respectively). The role of androgens was studied in 15 eugonadal male subjects (who presented for female role reassignment) by determining the effects of a novel nonsteroidal androgen receptor blocker, Anandron, on basal and LH-releasing hormone (LHRH)-stimulated serum LH/FSH levels; LH pulse frequency and amplitude; sex steroid and sex hormone-binding globulin levels; and serum PRL levels during an 8-week period. Basal and LHRH-stimulated LH levels and testosterone rose progressively during the first 6 weeks and reached a plateau thereafter, while estradiol levels continued to increase somewhat. The LH pulse amplitude and frequency had increased after 6 weeks (3.1 +/- 0.6 vs. 4.5 +/- 1.2 U/L and 4.4 +/- 2.4 vs. 6.6 +/- 1.1 pulses/7 h, respectively). Basal FSH levels were not affected while LHRH-stimulated FSH levels progressively decreased from 2 to 6 weeks, after which they did not change. Along with the rise of estradiol levels an increase of sex hormone-binding globulin and PRL levels occurred.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3102547 TI - Identification of inhibin secreted by cynomolgus monkey Sertoli cell cultures. AB - An inhibin was identified in the media of primary Sertoli cell-enriched cultures from the cynomolgus monkey, Macaca fascicularis, and some of its biochemical properties were studied. Conditioned monkey Sertoli cell culture medium (m-SCCM), when added to pituitary cells from 6-week-old male rats, inhibited the basal secretion of FSH but not that of LH. This specificity was lost after the addition of GnRH; mSCCM inhibited not only FSH but also LH release, determined by both RIA and mouse interstitial cell bioassay, from pituitary cells exposed for 6 h to 10 nM GnRH. FSH-inhibiting activity persisted when m-SCCM was boiled for 30 min, but activity was lost after incubation for 1 h at 37 C with 0.1% trypsin. m-SCCM inhibin activity was completely retained by Concanavalin A-Sepharose and could be eluted with 0.2 M alpha-methyl-D-glucoside. Gel filtration high pressure liquid chromatography with a Superose-12 column revealed inhibin activity between 20 60K, with the greatest activity at 40K. Our results indicate that primate Sertoli cells produce an inhibin-like factor which could play a role in controlling gonadotropin secretion in males. PMID- 3102549 TI - Influence of blindness on plasma luteinizing hormone, follicle-stimulating hormone, prolactin, and testosterone levels in prepubertal boys. AB - The aim of this study was to determine if changes in LH, FSH, PRL, and testosterone (T) secretion occur in blind prepubertal boys. Eight blind and six normal boys, aged 7-10 yr, living at an institute for blind subjects in Naples, Italy, were studied. Each had a combined GnRH (100 micrograms) and TRH (200 micrograms) test at 0800 h after nocturnal rest. Plasma LH, FSH, PRL, and T levels were measured by RIA. The blind boys had basal plasma LH, FSH, and T levels significantly lower than those in the normal boys (P less than 0.01 for all three); plasma PRL basal levels were similar to those in the normal boys. The blind boys, moreover, had lower peak LH, FSH, and PRL (P less than 0.01 for all three peaks) levels in response to GnRH-TRH. Our results, similar to those found by others in patients with delayed puberty or with hypogonadotropic hypogonadism, suggest that light stimuli influence neuroendocrine-gonadal activity in humans, as in other mammals; and in blind prepubertal boys, impaired hormone secretion could cause a delay of pubertal development or more severe hypogonadism. PMID- 3102548 TI - Neuronal source of plasma dihydroxyphenylalanine. AB - The source and significance of plasma levels of dihydroxyphenylalanine (DOPA), the precursor of the endogenous catecholamines, have been unknown. We measured arterial and venous plasma DOPA concentrations in healthy subjects at rest, patients who had undergone regional sympathectomies or were undergoing general anesthesia, and subjects during procedures (tilt, oral clonidine, or iv isoproterenol, yohimbine, trimethaphan, or diazepam) known to affect plasma norepinephrine levels. We also measured plasma DOPA in laboratory animals during anesthesia, after adrenalectomy, or after administration of alpha-methyl-para tyrosine, which competitively inhibits tyrosine hydroxylase, the intraneuronal enzyme catalyzing the rate-limiting step in catecholamine biosynthesis. In virtually all healthy subjects there was an arteriovenous increment in plasma DOPA (mean increase, 32%; P less than 0.001), whereas in sympathectomized patients there was not (mean decrease, 16%; P less than 0.001 compared with healthy subjects). Except for small decreases after clonidine treatment, none of the above procedures affected plasma DOPA levels. Plasma DOPA decreased during general anesthesia and returned to baseline upon reversal of the anesthesia. Adrenalectomy had no effect on plasma DOPA. alpha-Methyl-para-tyrosine decreased plasma DOPA by 62% (P less than 0.01). The results support the suggestion that DOPA can pass across sympathetic neuronal membranes to reach the general circulation. If so, then the regional rate of appearance of DOPA in plasma may be related to the regional rate of tyrosine hydroxylation. Conversely, DOPA taken up from the circulation may provide a source for catecholamine biosynthesis in tissues devoid of tyrosine hydroxylase. PMID- 3102550 TI - API QuadFERM+ with rapid DNase for identification of Neisseria spp. and Branhamella catarrhalis. AB - The QuadFERM+ system (Analytab Products, Plainview, N.Y.), a 2-h carbohydrate degradation method for the identification of Neisseria spp., was evaluated along with a rapid DNase test for confirmation of Branhamella catarrhalis. QuadFERM+ identified 100% of 82 N. gonorrhoeae and 96% of 54 N. meningitidis strains. The two misidentified meningococcal strains were biochemically atypical and were also misidentified by the conventional method. Of 26 N. lactamica strains, 25 (96%) were correctly identified. Of 21 Neisseria spp., 14 (67%) produced carbohydrate reactions in agreement with the conventional procedure, and 7 strains produced detectable acid in the QuadFERM+ from maltose and sucrose but not glucose. All 9 N. cinerea and 30 B. catarrhalis strains were asaccharolytic by QuadFERM+. The rapid DNase test was positive for all B. catarrhalis strains and negative for all other organisms. Two beta-lactamase-positive N. gonorrhoeae strains and 25 (93%) of 27 beta-lactamase-positive B. catarrhalis strains were detected by the 2-h acidometric beta-lactamase test on the strip. QuadFERM+ with rapid DNase is a simple and easily interpretable method for identification of these organisms in the clinical laboratory. PMID- 3102551 TI - Serodiagnosis of Streptococcus faecalis endocarditis by immunoblotting of surface protein antigens. AB - We describe a method for the serodiagnosis of Streptococcus faecalis in infective endocarditis which could be of value in culture-negative cases. Serum-grown cells of S. faecalis produced three major characteristic protein antigens (73,000, 40,000, and 37,000 molecular weight) which were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of solubilized whole cells. After electrophoretic transfer to a nitrocellulose membrane, these antigens were visualized by probing with serum from patients with endocarditis caused by S. faecalis. Serum from patients with endocarditis caused by other organisms did not react with the S. faecalis-specific antigens. This procedure should facilitate positive early diagnosis of S. faecalis endocarditis or establish its absence in culture-negative cases. PMID- 3102552 TI - Comparison of TRACK XI fluorometric immunoassay system with other serologic tests for detection of serum antibody to Brucella abortus in cattle. AB - The TRACK XI system (TRACK) is a commercially available fluorometric immunoassay system that has been adapted for the detection of antibodies to several antigens in various animal species. Serum antibodies to Brucella abortus were detected by TRACK and compared with those obtained from two primary binding assays (a fluorometric immunoassay [FIAX] and an enzyme-linked immunosorbent assay) and three standard serological tests (complement fixation, Rivanol precipitation, and CARD tests). A total of 298 serum samples were tested by each serological test. Of these serum samples, 134 were negative controls, 43 were from cattle 1 month after vaccination with B. abortus 19, and 121 were from cattle 10 to 12 weeks after a midgestational, intraconjunctival challenge with B. abortus 2308. The results of this study indicated that TRACK is both reproducible and accurate. The results compared favorably with those of other serological methods. TRACK is more rapid than either the enzyme-linked immunosorbent assay or FIAX system. TRACK was the most sensitive (96.3%) test, with a specificity of 100%. PMID- 3102553 TI - Bacteriologic surveillance of long-term-catheterized patients. PMID- 3102554 TI - Cultured human fetal astrocytes can be induced by interferon-gamma to express HLA DR. AB - Interferon-gamma (IFN-gamma) modulates the expression of Class II major histocompatibility antigens (MHC), thus providing a potential regulatory mechanism for local immune reactivity in the context of MHC-restricted antigen presentation. Within the central nervous system (CNS), the expression of MHC Class II antigens has been demonstrated on human reactive astrocytes and glioma cells. In order to investigate the modulation of HLA-DR on normal astrocytes, two cell lines were grown from a 20-week-old fetal brain. In situ none of the fetal brain cells expressed HLA-DR as determined by immunohistology on frozen tissue sections. The two cell lines, FB I and FB II, expressed GFAP indicating their astrocytic origin. FB I was HLA-DR negative at the first tissue culture passages, but could be induced to express HLA-DR when treated with 500 U/ml IFN-gamma. FB II was spontaneously HLA-DR positive in the early passages, lost the expression of this antigen after 11 passages and could also be induced to express HLA-DR by IFN-gamma. The induction of HLA-DR expression was demonstrated both by a binding RIA and by immunoprecipitation using a monoclonal antibody (MAB) directed against a monomorphic determinant of HLA-DR. The HLA-DR alloantigens were determined on FB II cells after IFN-gamma treatment, by immunofluorescence and by cytotoxicity assays, and were shown to be DR4, DR6, Drw52, DRw53 and DQwl. These results show that human fetal astrocytes can be induced to express HLA-DR by IFN-gamma in vitro and support the concept that astrocytes may function as antigen-presenting cells. PMID- 3102555 TI - Effect of dietary fat saturation on plasma lipoproteins and high density lipoprotein metabolism of the rhesus monkey. AB - Rhesus monkeys were fed corn or coconut oil-based diets for 3-6 mo to determine effects on the composition of all lipoprotein classes and on the metabolism of high density lipoproteins (HDL). Major findings included the following. Coconut oil feeding increased concentrations of all classes of plasma lipoproteins without altering lipoprotein size, suggesting an increase in particle number. The percentage of saturated fatty acids in the cholesteryl esters (CE) of low density lipoproteins (LDL) and HDL reached 40% with coconut oil feeding. This value probably constitutes a minimum estimate of the CE which were of intracellular rather than intraplasmic origin. The CE in LDL and HDL were nearly identical suggesting virtually complete equilibration by the core lipid transfer reaction. The CE in very low density lipoproteins, in contrast, were significantly more saturated than those in LDL and HDL irrespective of diet. Lower HDL levels on the corn oil diet were associated with higher fractional catabolic rates for both apolipoprotein A-I (0.42 vs. 0.31 d-1) and apolipoprotein A-II (0.45 vs. 0.30 d 1). PMID- 3102557 TI - Two new inherited defects of the thyroxine-binding globulin (TBG) molecule presenting as partial TBG deficiency. AB - Serum-denatured TBG (dnTBG) measured in 32 families deficient in native TBG (nTBG) was undetectable in all subjects with complete nTBG deficiency and was high in 2 of 16 families with partial nTBG deficiency. nTBG (in mean micrograms per decaliter +/- SD) in members of the Quebec and Montreal families, respectively were: 258 +/- 54 and 230 in affected men, 747 +/- 190 and 927 +/- 90 in affected women, and 1568 +/- 151 and 1300 +/- 195 in unaffected relatives. Corresponding mean dnTBG levels were: 14.3 +/- 2.9 and 21.3 in affected men, 8.6 +/- 1.0 and 11.6 +/- 3.1 in affected women, and less than 2.1 and less than 2.6 in unaffected relatives. All were euthyroid with normal free thyroxine and thyrotropin levels. In comparison to common type TBG, TBG-Quebec was more heat labile by 10 degrees C and TBG-Montreal by 12 degrees C. The degree of dnTBG elevation and nTBG lability at 37 degrees C were correlated (r = 0.99). Isoelectric focusing showed cathodal shift of all TBG bands: TBG-Quebec by 0.06 isoelectric points (pI) and TBG-Montreal by 0.02 pI. These two TBG variants represent different mutations most likely affecting the polypeptide chain of the molecule. Their inheritance is X-chromosome linked. The instability of these TBGs at 37 degrees C may lead to more rapid degradation in vivo resulting in low nTBG and high dnTBG concentrations in serum. PMID- 3102556 TI - Human adipocyte glucose transport system. Biochemical and functional heterogeneity of hexose carriers. AB - We have investigated glucose transport proteins in isolated human adipocytes. Using the cytochalasin B binding assay to measure glucose transporters in subcellular membrane subfractions, we found that insulin induced translocation of intracellular glucose transporters to the cell surface. Isoelectric focusing of glucose transporters photolabeled with [3H]cytochalasin B revealed two distinct glucose transporter isoforms in low density microsomes focusing at pH 5.6 and pH 6.4, but only the pH 5.6 isoform was detectable in plasma membranes and only the pH 6.4 form was found in the high density microsomes. Insulin recruited only the pH 5.6 glucose transporter from the low density microsomes to the plasma membrane with no effect on the pH 6.4 transporter isoform. The results suggest that the pH 6.4 species is an immature form of the glucose transporter initially located in the high-density microsome fraction, which then migrates to the low-density microsomes where it matures (converted to pH 5.6 species) and becomes available for insulin-mediated recruitment to the plasma membrane. PMID- 3102558 TI - Histidyl-proline diketopiperazine (His-Pro DKP) immunoreactivity is present in the glucagon-containing cells of the human fetal pancreas. AB - Histidyl-proline diketopiperazine (His-Pro DKP) cells in the pancreas of human fetuses aged between 12 and 19 wk were localized by the indirect antibody-enzyme method on semithin sections. To study their fine structure, two techniques were used: a superimposition technique consisting of comparison of the same cells in semithin and electron microscopic preparations, and an immunocytochemical technique on ultrathin sections using the unlabeled antibody peroxidase antiperoxidase method. Our results show that (a) the same cells are positive for both His-Pro DKP and glucagon/glicentin, (b) His-Pro DKP immunoreactive cells possess extremely electron-opaque secretory granules, implying that these cells correspond to the A cells, and (c) His-Pro DKP immunoreactivity is found over the secretory granules. We hypothesize that the two peptides His-Pro DKP and thyrotropin-releasing hormone (TRH) have independent origins, since TRH is found in the B cells. PMID- 3102560 TI - Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. AB - Gram-negative septicemia elicits multiple abnormalities of the coagulation system. Although products of coagulation can lead to clot formation, thereby potentiating organ damage, recent work has shown that low concentrations of thrombin can protect animals from the shock state. Because these amounts of thrombin also lead to formation in vivo of the anticoagulant enzyme, activated protein C, we examined the role of protein C in modulation of Escherichia coli shock in baboons. First, we infused activated protein C and lethal concentrations of E. coli organisms, which prevented the coagulopathic, hepatotoxic, and lethal effects of E. coli. Second, using an antibody to protein C we blocked protein C activation in vivo to determine if this influenced the response to lethal and sublethal concentrations of E. coli organisms. Under these conditions the response to lethal concentrations of E. coli organisms was made more severe and the response to sublethal concentrations of E. coli was made lethal. The coagulopathic, hepatotoxic, and lethal responses in this latter case were prevented by infusion of exogenous protein C. PMID- 3102562 TI - Light chains and the kidney. AB - Five cases of renal impairment caused by the deposition of light chains in the kidney in association with various immunoproliferative disorders are reported. Light microscopy, immunohistochemistry, and electron microscopy were undertaken and different clinical courses were studied, resulting in variable influences of treatment. Light chain deposition is an important cause of renal impairment and requires special histological techniques for its recognition. PMID- 3102561 TI - Aggregation of white cells and C-reactive protein: relation between these two indices in acute phase reaction. AB - The association between aggregates of leucocytes in blood drawn from patients with various inflammatory conditions and the serum concentration of C-reactive protein (CRP) was examined: serum concentration of CRP might contribute to the development of cellular aggregations. A total of 213 patients with various inflammatory or necrotic conditions were examined (including 31 women with normal pregnancy and 59 controls). A significant correlation between the degree of leucocyte aggregation and CRP concentration was noted in patients with bacterial infections and in a group of patients with various inflammatory conditions. In contrast, there was no correlation between the extent of leucocyte aggregation and CRP concentrations in patients with viral infections, malignancies, or pregnancy. The presence or absence of aggregated leucocytes can help in differentiating between the respective bacterial or viral infections. The serum concentrations of CRP were increased in both types of infection, although when a quantitative CRP assay was used, considerably higher concentrations were detected in bacterial diseases. PMID- 3102563 TI - Sodium valproate: its use in primary psychiatric disorders. AB - Sodium valproate has been reported to be effective in the treatment of recurrent major affective and schizoaffective disorders. The records of 36 consecutive patients with various psychiatric diagnoses, who received valproate at our center, were retrospectively reviewed. None of these patients displayed a diagnosable neurologic disorder or paroxysmal EEG activity. Sixteen (44%) of the 36 patients experienced a moderate to marked response to valproate. The diagnoses of bipolar or schizoaffective disorder and the presence of nonparoxysmal EEG abnormalities both predicted a favorable response. The authors conclude that valproate deserves further study as a possible treatment for major affective disorder. PMID- 3102564 TI - Bupropion treatment of refractory depression. PMID- 3102559 TI - sn-1,2-Diacylglycerols and phorbol diesters stimulate thromboxane synthesis by de novo synthesis of prostaglandin H synthase in human promyelocytic leukemia cells. AB - We studied the regulation of thromboxane (TX) synthesis in promyelocytic leukemia cells during macrophage differentiation. Cells treated with 12-O tetradecanoylphorbol-13-acetate (TPA) showed rates of TXB2 synthesis from exogenous arachidonic acid that exceeded that of control cells by a factor of up to 81. Cells treated with sn-1,2-dioctanoylglycerol (diC8) showed similarly high TXB2 synthesis rates when diC8 was added concomitantly with a subthreshold concentration of TPA or when given in multiple doses. These activities depended on de novo synthesis of prostaglandin H (PGH) synthase because: microsomal PGH synthase activity showed large increases in Vmax values, and mass measurements of PGH synthase revealed the presence of PGH synthase in differentiating cells whereas the enzyme was undetectable in control cells. These results indicate that macrophage differentiation is associated with stimulation of TXB2 synthesis that requires both activation of protein kinase C and de novo synthesis of PGH synthase. PMID- 3102565 TI - Myasthenia gravis unmasked by lithium carbonate. PMID- 3102566 TI - Fine structural studies of growth-hormone-releasing-factor (GRF)-immunoreactive neurons and their synaptic connections in the guinea pig arcuate nucleus. AB - The fine structure of neurons containing human growth-hormone-releasing factor (hGRF) immunoreactivity located in the arcuate nucleus of the guinea pig was studied by means of the preembedding immunohistochemical technique. The perikaryon of labeled neurons was fusiform or ovoid; the nucleus was regular in shape and contained a prominent nucleolus. The main ultrastructural features of the hGRF-immunoreactive neurons were the presence of numerous labeled secretory granules (100-120 nm in diameter) and the abundance and the enlargement of the organelles involved in the synthesis of the peptides: a well-developed rough endoplasmic reticulum and a conspicuous Golgi apparatus. Synaptic inputs were observed on immunoreactive perikarya but, above all, on the labeled dendrites. The unstained presynaptic nerve endings most often contained only small clear vesicles and formed symmetrical contacts. In rare cases, the presynaptic terminals exhibited both small clear and large dense vesicles and constituted asymmetrical contacts. Immunoreactive nerve endings were also observed in this area: the synaptic boutons contained large, stained vesicles and small, unlabeled, clear vesicles. These axon terminals made synaptic contacts with unstained dendritic processes; the contacts were symmetrical. The results indicate that hGRF-immunoreactive neurons of the guinea pig arcuate nucleus present morphological features of neuroendocrine cells. Moreover, the presence of hGRF-labeled nerve endings in the arcuate nucleus itself suggests that a substance related to hGRF might be a neuromodulator, at least in this area. PMID- 3102567 TI - Distribution of cholecystokinin-immunoreactive cell bodies in the male and female rat: I. Hypothalamus. AB - The hypothalamic distribution of cholecystokinin-immunoreactive (CCKI) cell bodies in colchicine-treated male and female rats was studied. Immunoreactive neurons were visualized along the anterior two-thirds of the third ventricle but were especially numerous in the preoptic periventricular nucleus. Dense aggregations of CCKI cells were found in the anterior magnocellular, posterior magnocellular, medial parvicellular, and posterior parvicellular divisions of the paraventricular nucleus. Both the supraoptic nucleus and the central, cell-dense part of the dorsomedial nucleus contained large numbers of CCKI cells. CCKI cells in the preoptic periventricular nucleus were more numerous in the female, as was a population of labeled cells in the dorsal medial preoptic area. However, CCKI cell bodies in this part of the medial preoptic area were larger in males than in females. Males had more CCKI cells in the central part of the medial preoptic nucleus and in the posterior magnocellular subdivision of the paraventricular nucleus. Both males and females had similar numbers of immunoreactive cells in the anterior magnocellular and the parvicellular divisions of the paraventricular nucleus as well as in the anterior hypothalamus, dorsal areas, dorsomedial nucleus, and supramammillary region. These data provide morphological evidence for a sexually differentiated hypothalamic CCKI system. PMID- 3102569 TI - Is cost-effective medicine possible? PMID- 3102568 TI - Xanthogranulomatosis in an adult: lipid analysis of xanthomas and plasma. AB - Xanthomatosis in the absence of hyperlipidemia is unusual but has been associated with compositional abnormalities of lipoprotein particles. An adult who developed juvenile xanthogranulomatosis in association with oral contraceptive ingestion is reported. Plasma lipids and lipoprotein electrophoresis were normal, as in a few other patients reported with this disorder. However, analysis of cutaneous xanthoma and plasma by thin-layer and gas-liquid chromatography revealed that cholesterol was the principal lipid in xanthoma and that there were no unusual sterols in plasma or tissue. Possible mechanisms of xanthoma formation are discussed. Thus juvenile xanthogranulomatosis should be considered in adults with normolipemic xanthomatosis. PMID- 3102570 TI - Platelike cutaneous osteoma. AB - Platelike osteoma cutis is a rare lesion that is most often congenital. An 85 year-old man developed a plate, or sheet, of subcutaneous bone in an area previously affected by morphea. The sheet of bone was visualized with a variety of imaging technics, including xerography, computed tomography, and radionuclide bone scans. PMID- 3102571 TI - Carbon dioxide laser in the treatment of porokeratosis. PMID- 3102573 TI - Staff development: practice ethics. PMID- 3102572 TI - Comparison of initial biodistribution patterns of Gd-DTPA and albumin-(Gd-DTPA) using rapid spin echo MR imaging. AB - The initial biodistribution patterns of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), an extracellular fluid contrast agent, and human serum albumin, paramagnetically labeled with 19 Gd-DTPA groups and used as an intravascular agent, were compared in the brain, heart, liver, and major mediastinal vessels of rats. Repeated 4 s spin echo images acquired after injection of 0.2 mmol/kg Gd DTPA demonstrated a maximum enhancement between 15 and 25 s of 57% in brain, 307% in heart, 220% in liver, 83% in subcutaneous tissue, and 380% in slowly flowing blood in mediastinal vascular structures. In the following 55 s there was a continuous decrease (average 45%) in signal intensity in each tissue except brain. Albumin-(Gd-DTPA), injected at a four times lower molar dose (0.045 mmol/kg) with respect to Gd-DTPA, demonstrated maximal enhancement of brain by 34%, heart by 237%, liver by 186%, and blood in mediastinal vessels by 325%. Gadolinium-DTPA, which rapidly diffuses from the small vessels into the interstitial space, was noted to accumulate in solid tissues and subsequently to be partially eliminated within 70 s of administration. Signal enhancement achieved with albumin-(Gd-DTPA) remained at a constant level over the 70 s observation period. These data further support the notion that albumin-(Gd-DTPA), due to its predominantly intravascular distribution, might be applied advantageously for the assessment of perfusion and blood-volume disorders. PMID- 3102574 TI - New technology for educating nurses. PMID- 3102575 TI - Business ethics: implications for continuing education/staff development practice. PMID- 3102576 TI - Acquiring and using power effectively. PMID- 3102577 TI - Environmental management: creating a learning ambiance. PMID- 3102578 TI - The Cervero model. PMID- 3102580 TI - Economics, productivity and effectiveness. PMID- 3102579 TI - In search of the impact of continuing education. PMID- 3102582 TI - Mechanisms of heat inactivation of a proteinase from Pseudomonas fluorescens biotype I. AB - Heat inactivation of a metalloproteinase, isolated from Pseudomonas fluorescens biotype I strain 112, was investigated in the temperature ranges 50-60 degrees C and 90-140 degrees C. At 90 degrees C the denaturation of the enzyme followed first-order kinetics with a decimal reduction time of 110 min and a velocity constant K of 3.5 X 10(-4) S-1. Activation energy Ea was 100 kJ/mol for this temperature range. In the 50-60 degrees C region the proteinase was inactivated by autolysis, as shown by electrophoresis and gel filtration. At 55 degrees C the decimal reduction time was approximately 22 s, at 57 degrees C it was 8 s. Rapid inactivation at 55 degrees C was only possible if the enzyme was heated from lower temperatures, but not if cooled down from 90 degrees C. This is due to a conformational change of the protein at this temperature. A model for the description of heat inactivation in the two temperature ranges is proposed. PMID- 3102581 TI - The value of blood group-specific lectin and endothelial associated antibodies in the diagnosis of vascular proliferations. AB - Blood vascular and lymphatic tumors were evaluated immunohistochemically by studying a spectrum of endothelial associated antigens. UEA-1 lectin reacted with the tumor cells of one patient with malignant angioendothelioma in the non metastatic stage. However, when metastasis occurred, the binding sites of this lectin completely disappeared from the surface of the tumor cells in both original and metastatic lesions, suggesting the loss of blood group H antigen from the tumor cells could be used as an indicator of metastasis in this tumor. Reaction with anti-HLA-A, B, C, intense in normal blood vessels, remained intensely positive in pyogenic granuloma and Kaposi's sarcoma, whereas it did not react with normal lymphatics and lymphangioma. This indicates that anti-HLA-A, B, C is useful in differentiating blood vascular structures from lymphatic structures in both normal and pathological conditions. OKM5 reacted intensely with benign hyperplasias in pyogenic granuloma, while barely reacting with proliferating parts in Kaposi's sarcoma, suggesting the difference in staining patterns can be used to distinguish vascular proliferation or malignancy. Reaction with anti-Type IV collagen and anti-laminin was intense in normal blood vessels, pyogenic granuloma and Kaposi's sarcoma, whereas reaction with these antibodies in normal lymphatics was patchy and irregular in its thickness. PMID- 3102583 TI - To screen or to vaccinate? A decision analysis for rubella prevention on campus. PMID- 3102584 TI - Comparative properties of two clinical preparations of recombinant human tissue type plasminogen activator in patients with acute myocardial infarction. AB - The biologic properties of two clinical preparations of recombinant human tissue type plasminogen activator were studied in 52 patients with acute myocardial infarction. The first preparation (G11021) has been used in all clinical trials reported to date, whereas the second preparation (G11035) is now produced for future clinical use. When both preparations were infused intravenously for 90 minutes at rates of 4 to 11 micrograms/kg per min, plateau levels of the drug in plasma ranged from 0.52 +/- 0.15 to 1.8 +/- 0.4 micrograms/ml and were linearly correlated with the infusion rate. However, G11035 yielded plasma levels that were approximately 35% lower than those obtained with G11021 (p less than 0.025). The postinfusion disappearance rate of the drug from plasma could be described by a two compartment disposition model with the following pharmacokinetic variables. For G11021, an alpha half-life of 4.1 to 6.3 minutes, a beta half-life of 41 to 50 minutes, a central compartment volume of 3.5 to 5.4 liters, a total distribution volume of 28 to 44 liters and a plasma clearance of 450 to 640 ml/min. For G11035 these variables were 3.6 to 4.6 minutes, 39 to 53 minutes, 3.8 to 6.6 liters, 27 to 40 liters and 520 to 1,000 ml/min, respectively, indicating that G11035 is cleared more rapidly from the circulation. G11021 at 4 micrograms/kg per min and G11035 at 7 micrograms/kg per min did not effectively produce thrombolysis. A coronary reperfusion rate of 81% (13 of 16 patients) was obtained with 5.3 micrograms/kg per min of G11021 and a rate of 86% (6 of 7 patients) was obtained with 9.4 micrograms/kg per min of G11035.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102586 TI - The use of respiratory quotient to determine the efficacy of nutrition support regimens. AB - Respiratory quotient (RQ) is an indicator of fuel utilization. This study examined the RQs of patients receiving intensive nutrition support to assess the frequency with which net fat synthesis occurred, as determined by RQs greater than 1.0. One hundred twelve RQs were calculated from data obtained using indirect calorimetry. Seventy-four measurements were made while patients were receiving parenteral nutrition--55 with glucose and amino acid (GAAPN) and 19 with glucose, fat, and amino acid (GFAAPN). Thirty-eight measurements were made while patients were receiving either oral or nasoenterally administered carbohydrate, fat, and protein in the form of standard hospital diets or liquid defined formula diets (CFPEN). The mean RQ of the GAAPN patients was significantly higher than those of both the GFAAPN and the CFPEN patients. RQs were greater than 1.0 in a significantly greater number of the GAAPN patients than the GFAAPN or CFPEN patients. The route of nutrient intake did not influence energy nutrient utilization, as determined by RQ. This study suggests that nutrition support regimens containing fat, in addition to carbohydrate and protein, are more efficiently utilized to meet the energy requirements of hospitalized patients than are regimens containing only glucose and amino acid. PMID- 3102585 TI - Sustained release verapamil, a once daily preparation: objective evaluation using exercise testing, ambulatory monitoring and blood levels in patients with stable angina. AB - The efficacy of a once daily, sustained release formulation of verapamil (Verapamil SR, 360 mg) was evaluated in 19 patients with chronic angina pectoris using a double-blind placebo-controlled crossover protocol. Evaluation by exercise testing, 24 hour electrocardiographic ambulatory monitoring and blood drug level assays was performed at the end of each 2 week phase, 21 to 23 hours after the last dose. After the crossover protocol, all patients were given sustained release verapamil for 4 weeks and the evaluation was repeated. Exercise time (mean +/- SEM) increased from 7.4 +/- 0.6 minutes with placebo to 9.6 +/- 0.8 minutes with verapamil (p less than 0.001) and to 9.5 +/- 0.7 minutes (p less than 0.001) after 4 weeks of therapy. The mean time to 1 mm ST depression also increased significantly, from 4.5 +/- 0.4 and 4.8 +/- 0.5 minutes in bipolar leads CM5 and CC5, respectively, with placebo, to 5.5 +/- 0.6 (p less than 0.05) and 6.2 +/- 0.5 minutes (p less than 0.01) with verapamil. Maximal ST depression and rest and peak heart rates were not altered significantly. The mean rate pressure product was 208 +/- 9.9 with placebo and decreased to 189 +/- 7.7 (p less than 0.05) with verapamil but rose to 200.6 +/- 10.4 (p = NS) after 4 weeks of therapy. The mean hourly heart rates were lower with the drug than with placebo throughout the 24 hour period but there was no significant bradycardia, arrhythmia or heart block.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102587 TI - Does nutrition affect surgical outcome? PMID- 3102588 TI - Physician-directed long-term home health care for the elderly--a century-long experience. PMID- 3102589 TI - Fabry's disease. PMID- 3102590 TI - Ocular manifestations of Fabry's disease. PMID- 3102592 TI - Nursing care of the elderly. The DRG influence. PMID- 3102591 TI - Age-related changes in rat muscle glycogen synthase activity. AB - This study was designed to evaluate effects of aging on glycogen synthase activity in rat skeletal muscle. Total enzyme activity was shown to be significantly, (p less than .001) lower in tensor fascia latae, biceps femoris, and soleus muscle obtained from 24-month-old compared with 2-month-old rats. Similarly, values for the active form of enzyme were significantly lower, (p less than .001) in all three muscle types of 24-month-old compared with 2-month-old rats. This age-related decline in glycogen synthase activity was not due to a reduction in the affinity of the enzyme for its activator (glucose-6-phosphate) and was independent of the concentration of substrate (UDP-glucose) in the assay system. Because similar age-related changes were seen when enzyme activity was expressed per milligram of muscle protein or per gram of muscle tissue, the fall in enzyme activity was not a simple function of an age-related decline in muscle mass. Glycogen levels also were reduced significantly in tensor fascia latae, biceps femoris, and soleus of 24-month-old rats compared with 2-month-old rats, p less than .001. These results document an age-related change in a key enzyme regulating glycogen metabolism in muscle. PMID- 3102593 TI - Ligand-dependent redistribution of the IgA receptor on cultured rat hepatocytes and its disturbance by cytochalasin B. AB - The topography and dynamics of IgA-secretory component (SC) complexes on the surface of cultured hepatocytes and its disturbance by cytochalasin B were investigated using the colloidal gold technique in conjunction with surface replication. The distribution of IgA-gold conjugates after incubation at 4 degrees C was similar in normal and cytochalasin B-treated hepatocytes and was characterized by diffusely scattered single and clustered particles, the latter often associated with coated pits. After raising the temperature to 37 degrees C, redistribution of particles and their gradual uptake into coated vesicles was observed in control cultures. This ligand-induced redistribution led to a progressive gathering of single and grouped particles in larger clusters (50-200 particles), which appeared to be the site of the most intensive endocytotic activity. In contrast, huge patches of IgA-gold conjugates were formed at the cell periphery of cytochalasin B-treated hepatocytes within 20-60 min at 37 degrees C, while central areas were cleared. Patch formation was triggered by binding of both unlabeled and labeled IgA, but could not be observed with the unoccupied receptor as demonstrated by gold-labeled antibodies against SC. These results show that the topography of SC is markedly changed by binding of its ligand, IgA, and suggest that the dynamics of the IgA-SC complexes in hepatocyte plasma membrane are affected by microfilaments. PMID- 3102594 TI - Accessory cell independent proliferation of human T4 cells stimulated by immobilized monoclonal antibodies to CD3. AB - The capacity of the monoclonal antibodies (Mab) 64.1 and OKT3 directed at CD3 molecules to induce T4 cell proliferation and interleukin 2 (IL 2) production was examined. Each was tested in soluble form or was immobilized by adhering it to the wells of plastic microtiter wells. Soluble anti-CD3 did not induce proliferation of accessory cell (AC)-depleted T4 cells. In contrast, immobilized anti-CD3 induced T4 cell IL 2 production and proliferation in the complete absence of AC. When T4 cells were stimulated with high density immobilized anti CD3, responses did not require AC, IL 2, or Mab directed at the Tp44 molecule (9.3). In contrast, responses stimulated by lower densities of immobilized anti CD3 were enhanced by IL 2, AC, and 9.3, and with even lower densities of immobilized anti-CD3 proliferation, required these additional signals. A variety of other immobilized Mab directed at T cell surface proteins including class I major histocompatibility complex encoded gene products, CD2, CD5, 4F2, and Tp44, did not induce proliferation even in the presence of IL 2. Anti-CD4 Mab (66.1) inhibited immobilized anti-CD3-stimulated T4 cell responses, with a greater degree of inhibition noted when lower densities of immobilized anti-CD3 were used to stimulate T4 cells. The data demonstrate that stimulation of T4 cells by anti CD3 is completely AC independent when the antibody is immobilized onto a surface. Furthermore, the results indicate that maximal stimulation requires multiple interactions with anti-CD3 without internalization of the CD3 molecule. The observation that additional signals are required to support T4 cell proliferation when the density of immobilized anti-CD3 is diminished suggests that these are necessary only when insufficient interactions with the CD3 molecule have occurred to transmit a maximal activation signal to the cell. Finally, the results indicate that anti-CD4 provides a direct inhibitory signal to the T4 cell, the effect of which is inversely proportional to the intensity of the activation signal. PMID- 3102596 TI - HLA DR, DQ, and DP antigen expression in rheumatoid synovial cells: a biochemical and quantitative study. AB - Because an increased expression of HLA class II antigens appears to be a central feature in local lesions of rheumatoid arthritis (RA), we have developed specific tools to quantify Ia expression in RA at both the protein and mRNA levels. An original dot immunobinding assay and a quick blot hybridization with chain specific HLA class II probes allowed quantification of HLA DR antigens and chain transcripts on small-size samples of adherent synovial lining cells (ASLC) from normal individuals or RA patients. These methods associated with Western blot techniques detecting class II and beta-chain expression showed that ASLC from RA patients freshly put in short-term culture expressed greater amounts of class II transcripts and proteins than ASLC from controls. Class II proteins and mRNA rapidly disappeared in culture. Recombinant interferon-gamma (rIFN-gamma) induced their re-expression. A study of the kinetics and levels of the HLA-D products showed similar patterns of activation in RA patients and controls. A qualitative analysis of HLA class II antigens synthesized in ASLC after rIFN-gamma induction was performed by two-dimensional gel electrophoresis. It revealed a normal pattern for alpha- and beta-chains in ASLC from normal and RA patients, thus eliminating the possibility that abnormal protein structure of Ia antigen expressed on ASLC is responsible for the activation of T cell immune responses in RA. Nevertheless, the invariant chain exhibited a particular pattern in ASLC with additional basic spots, and this might interfere with transport and glycosylation of HLA class II antigens in such cells. PMID- 3102595 TI - Comparison of T cell receptor gene rearrangements in patients with large granular T cell leukemia and Felty's syndrome. AB - Felty's syndrome (FS) refers to the occurrence of rheumatoid arthritis, splenomegaly, and neutropenia. A subset of these patients has recently been described with a chronic T cell leukemia of large granular lymphocytes (LGCL). To examine the spectrum of lymphocyte abnormalities in FS and LGCL, we examined phenotypic and genotypic properties of lymphocytes from eight FS patients. In two of these FS patients, we observed an elevated proportion of T cells with an unusual phenotype (CD3+/Leu-7+/Leu-8-/CR3+) (46 +/- 5% of mononuclear cells). The FS lymphocytes had large granular morphology on Wright-Giemsa stain and were active in antibody-dependent cellular cytotoxic activity. This phenotype, morphology, and activity was similar to LGCL patients except that the latter T cells additionally expressed the Fc-IgG receptor recognized by monoclonal antibody Leu-11 (CD 15). In the remaining six FS patients, the proportion of CD3+/Leu-7+/CR 3+ T cells was only 10 +/- 8%, which was not significantly different from age-matched normal subjects (6.6 +/- 2.2%). To determine the clonality of T lymphocytes in FS and LGCL, we examined DNA for rearrangements of the T cell antigen receptor beta-chain (Ti beta) and gamma-chain (Ti gamma) genes by using Southern blotting techniques. We found a clonal rearrangement of the Ti beta 1 and Ti gamma genes in both LGCL patients. In contrast, no clonal rearrangements of Ti beta or Ti gamma genes were detected in lymphocytes from the FS patients. These results indicate that FS patients are heterogeneous in their phenotype and that one subset exhibits polyclonal expansion of an unusual lymphocyte subset. PMID- 3102597 TI - Activation through CD3 molecule leads a number of human T cell clones to induce IgE synthesis in vitro by B cells from allergic and nonallergic individuals. AB - Seventy-eight clones established from tonsillar T lymphocytes of two nonallergic children were tested under different experimental conditions for their ability to induce in vitro IgE synthesis by B cells from allergic or nonallergic donors. After 24 hr preactivation with phytohemagglutinin (PHA), 11 out of 32 CD4+ clones from the first and 17 out of 36 CD4+ clones from the second tonsil donor showed the ability to induce IgE synthesis in vitro by B cells from both allergic and nonallergic individuals, whereas none of 10 CD8+ clones nor T blasts of PHA induced cell lines obtained from unfractionated T cell suspensions of the same tonsils had such an effect. Seven of the 11 T cell clones from the first tonsil donor active on IgE production after pre-activation with PHA also induced IgE synthesis in vitro by nonallergic and allergic B cells upon stimulation with anti CD3 monoclonal antibody. Under the same experimental conditions, virtually all of the T cell clones able to induce IgE synthesis in vitro by target B cells showed the ability to stimulate IgG and IgM production as well. T cell clones were also established from the peripheral blood of a nonallergic donor and were tested for their ability to induce IgE synthesis in autologous B cells. After preactivation with PHA, seven out of 35 CD4+ clones induced the production of detectable amounts of both IgE and IgG in autologous B cells. The addition to the cultures of PHA-stimulated unfractionated T cells inhibited in a dose-dependent manner the IgE but not the IgG synthesis induced by an autologous helper T cell clone in autologous B cells. Taken together, these data indicate that a remarkable proportion of human T cell clones upon triggering of the CD3 molecular complex were able to provide help for the synthesis of IgE in B cells from both allergic and nonallergic individuals. The successful induction of IgE synthesis by single T cell clones was apparently related to the lack of concomitant suppressor activity to which IgE-producing cells appeared to be exquisitely sensitive. PMID- 3102598 TI - IgG anti-lymphocyte antibodies in systemic lupus erythematosus react with surface molecules shared by peripheral T cells and a primitive T cell line. AB - IgG anti-T cell autoantibodies are common in SLE serum, react preferentially with activated lymphocytes, and exert early-phase inhibitory effects on antigen induced T cell proliferation. Little is known about the target molecules in this system, however, because the low titer and low avidity of the most interesting antibodies limit their utility in conventional immunoprecipitation analyses. Therefore, Western blotting was used to demonstrate binding of IgG in anti-T cell antibody-positive SLE sera to four surface membrane molecules shared by peripheral T cells and HSB-2 cells. Molecules of Mr 90,000 and 55,000 were particularly reactive: each target was stained by IgG anti-lymphocyte antibodies in 11 patient sera (approximately 85%) in the panel. Targets of Mr 37,000 and 105,000 were encountered less frequently (six of 13 and one of 13 patients, respectively). It is unlikely that alloantibodies contributed to the staining patterns observed because reactivity with the four targets was consistently present when cell preparations from multiple unrelated donors were examined. The target molecules were localized to the plasma membrane by whole cell absorption/elution experiments, by the failure of chromatin (DNA/histone) to absorb antibodies to these antigens, and through the use of purified membranes as substrate for Western blotting. With the possible exception of the 105,000 Mr molecule, which is a major target in the IgM anti-T cell antibody system, evidence for the existence of neoantigens as a basis for increased reactivity of SLE IgG with activated T cells was not obtained. The identity of the IgG antibody reactive molecules with respect to known T cell antigens was not determined, although evidence against the existence of antibodies to Tac (IL 2 receptor) and the transferrin receptor was obtained in monoclonal antibody pre-clearing experiments. Nonetheless, the observation that a limited number of major IgG autoantibody target antigens on activated peripheral T cells are shared by HSB-2 cells, a primitive T cell line expressing few of the differentiation antigens characteristic of mature T cells, should provide a basis for more definitive characterization of antigens in this system in the future. PMID- 3102600 TI - Characterization of monoclonal nonspecific suppressor factor (MNSF) with the use of a monoclonal antibody. AB - The secretion of immunoglobulin (Ig) from cultured mononuclear cells by lipopolysaccharide (LPS) stimulation is inhibited by monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by murine T cell hybridoma. In an attempt to develop a murine monoclonal antibody (MAb) with specific reactivity against MNSF, a cell fusion technique that incorporated immune murine splenocytes and HAT-sensitive murine myeloma cells was used. Cross-reactivity experiments confirmed that the MAb (MO6) does not bind to unrelated proteins such as bovine serum albumin, mouse IgG, and murine interferon-gamma (IFN-gamma). There are no effects when anti-IFN-gamma antibodies are used with MNSF. As far as biological activity is concerned, MO6 inhibits in vitro the activity of MNSF in terms of the Ig secretion from cultured lymphocytes. By using MO6, affinity chromatography and immunoblotting were performed. The MNSF on the SDS-PAGE showed a band with m.w. of approximately 70,000, indicating the formation of an aggregate in saline; but after treatment with 0.4 M pyridine-acetic acid buffer, separate bands of 24,000 and 16,000 daltons were evident. Therefore MO6 recognizes 70,000 and both 24,000 and 16,000 daltons. Thus we confirmed by using this MAb and affinity chromatography, the existence of human counterpart, human nonspecific suppressor factor (hNSF), in supernatant from concanavalin A-stimulated T cells. When hNSF was fractionated by high pressure liquid chromatography (HPLC), the activity was found in a region corresponding to 70,000 daltons. However, when fractionated in pyridine-acetic acid buffer, hNSF activity was distributed in a slightly wider range of 15,000 to 30,000 daltons. Physicochemical analysis showed that the purified hNSF is resistant to either heating at 56 degrees C or to 2 mercaptoethanol treatment; however, it is labile to acidification at pH 2.0 and is also sensitive to protease treatment, the characteristics of which were similar to those of murine MNSF. Thus MO6 was confirmed to be a pertinent tool for isolation of hNSF, as well as for murine MNSF. PMID- 3102599 TI - Functional alterations of macrophages in autoimmune MRL-lpr/lpr mice. AB - To assess the role of macrophages (MAC) in the pathogenesis of systemic lupus erythematosus, we investigated functional aspects of peritoneal MAC obtained from autoimmune MRL/MpJ-lpr/lpr (MRL-lpr) mice. MRL-lpr and control C3H/HeN MAC were obtained from untreated mice or mice injected i.p. with 1 ml of 10% sterile peptone 3 days before cell harvest. MRL-lpr mice had significantly more peritoneal cells (MAC and lymphocytes) than did control mice. In endotoxin-free conditions, MRL-lpr MAC were similar to C3H/HeN MAC in their baseline, and IFN gamma and/or LPS enhanced cytolysis of 3T12 fibrosarcoma tumor cells. Compared with C3H/HeN MAC, MRL-lpr MAC had a significant increase in antibody-dependent cellular cytotoxicity activity against sheep erythrocytes. This enhanced activity was not accompanied by a similar increase in adherence and/or phagocytosis of the same targets. Finally, in response to phorbol myristate acetate stimulation, both resident and peptone-induced MAC from MRL-lpr mice produced significantly more hydrogen peroxide than did those from control mice. These results indicate that MAC from MRL-lpr mice display features of selective "activation", and suggest that MAC or their products may play a role in the pathogenesis of inflammatory disorders seen in autoimmune diseases. PMID- 3102601 TI - Demonstration of up-regulated IL 2 receptor expression on an in vitro cloned BCL1 subline. AB - We have established BCL1 CL-3 cells capable of responding to B15-TRF and interleukin 2 (IL 2). This clone has both high affinity and low affinity receptors for IL 2 (IL 2R), but IL 2 by itself did not stimulate either proliferation or immunoglobulin (Ig) secretion. B15-TRF, which possesses both growth and differentiation activity, causes an increase in size of CL-3 cells and renders CL-3 cells responsive to IL 2, including an increased expression of IL 2R (eight-fold to 10-fold) and the differentiation of CL-3 cells into Ig secretion (60 to 80% of cultured cells). CL-3 cells pretreated with B15-TRF for 12 hr become competent to respond to IL 2 by up-regulation of IL 2R within 12 hr. In contrast CL-3 cells pretreated with IL 2 for 12 hr required 24 hr B15-TRF stimulation to result in IL 2R up-regulation. Thus the ordered action of B15-TRF and IL 2 is the most effective operational pathway for the up-regulation of IL 2R. This IL 2-mediated IL 2R up-regulation and induction of Ig synthesis depends upon the concentration of IL 2 in the culture. Both responses seem to be caused by IL 2 molecules bound to high affinity IL 2R. However, the possibility of involvement of low affinity IL 2R can not be vigorously excluded. In fact the level of IL 2 required for a response is far higher than that needed for activated T cell proliferation. This cloned BCL1 subline promises to be a useful tool for studying the regulation and mechanisms of B cell responses. PMID- 3102602 TI - Role of T cell-replacing factor (TRF) in the murine B cell differentiation: induction of increased levels of expression of secreted type IgM mRNA. AB - T cell-replacing factor (TRF) is known to play a critical role in the regulation of B cell growth and differentiation. In this study, the role of TRF in the expression of mRNA for both IgM and IgG1 class was investigated. The TRF was purified from cellfree supernatants from a T cell hybridoma, B151K12. RNA was isolated from chronic B cell leukemia (BCL1) cells, DNP-KLH-primed B cells, or normal B cells cultured with or without LPS, and LPS plus TRF or LPS plus BSF-1. The steady state level of isotype-specific mRNA was assessed by Northern blot analysis with a mu-specific or a gamma 1-specific probe. It was demonstrated that BCL1 and purified B cells cocultured with TRF expresses increased levels (twofold and fourfold, respectively) of secreted forms of mu mRNA. Purified B cells from DNP-KLH-primed mice also expressed increased levels (twofold to fourfold) of mu as well as gamma 1 mRNA for secreted form by stimulation with TRF. Total expression of mu mRNA, however, was approximately threefold higher than that of gamma 1 mRNA. The stimulation of normal B cells with LPS plus TRF induced an increase in the levels of mu mRNA and gamma 1 mRNA expression, fourfold and threefold, respectively. However, the levels of gamma 1 mRNA expression was one third of that induced in B cells stimulated with LPS plus BSF-1. These results indicate that TRF preferentially induces increased levels of secreted type of mu mRNA and induces less gamma 1 mRNA than BSF-1. The differential role of TRF from BSF-1 in the expression of Ig mRNA will be discussed. PMID- 3102603 TI - Regulation of arachidonic acid metabolism in resident and BCG-activated alveolar macrophages: role of lyso(bis)phosphatidic acid. AB - To dissect mechanisms of arachidonic acid (20:4) metabolism in pulmonary alveolar macrophages (PAM), two distinct cell populations were investigated, resident and BCG-activated rabbit alveolar macrophages. After purified resident PAM were labeled overnight with [3H]20:4, radioactivity was localized primarily within lyso(bis)phosphatidic acid (L(bis)PA) (13.1% +/- 1.7), phosphatidylethanolamine (PE) (22.8% +/- 0.8), and phosphatidylcholine (PC) (26.7% +/- 1.7), with lesser amounts recovered in phosphatidylserine plus phosphatidylinositol (PS/PI) (9.2 +/ 0.8%). By contrast, analysis of the phospholipid classes from prelabeled BCG activated PAM revealed that the amount of [3H]20:4 contained in L(bis)PA was profoundly decreased (4.7% +/- 0.4), p less than 0.003), whereas [3H]20:4 contained within other BCG phospholipids remained unchanged. Moreover, L(bis)PA, which composed 18.6% +/- 1.2 of the total phospholipid phosphorus of resident PAM, was reduced to 4.1% +/- 0.1 in BCG-activated macrophages (p less than 0.01). Phospholipase A2 from snake venom or from pancreas failed to release 20:4 from L(bis)PA, and lipase (phospholipase A1) from Rhizopus delmar liberated no more than one-third of this arachidonate. These results suggest that much of the arachidonate is not mobilized by classical phospholipases A1 and A2. When [3H]20:4-labeled PAM were stimulated with 1 microM 12-O-tetradecanoyl-phorbol-13 acetate (TPA), a loss of [3H]20:4 was observed from L(bis)PA, PE, PC, and PS/PI, with a concomitant increase in the synthesis of Hete and leukotriene C4. BCG activated PAM exposed to either TPA or 3.8 microM calcium ionophore A23187 liberated [3H]20:4 solely from PE and PC, with diminished 20:4 oxidative metabolism. Analysis of the specific radioactivities of phospholipids obtained from resident PAM prelabeled with [3H]20:4 or [32P]i demonstrated that the specific activity of [32P]L(bis)PA was negligible, whereas that of [3H]20:4 was quite high. In addition, L(bis)PA deacylation induced by TPA in resident PAM was always accompanied by a corresponding loss of [3H]20:4 from phosphatidylinositol (PI), suggesting that metabolism of this novel phospholipid proceeded by a deacylation-reacylation reaction rather than by de novo synthesis. BCG-activated PAM, which exhibited depressed eicosanoid formation, consistently failed to deacylate [3H]20:4 from L(bis)PA or PI. These studies demonstrate that, unlike 20:4 derived from PE and PC by BCG-activated PAM, L(bis)PA may indeed provide a novel source of 20:4 that is tightly coupled to the lipoxygenase pathway. PMID- 3102604 TI - Comparison of subcellular activation of the human neutrophil NADPH-oxidase by arachidonic acid, sodium dodecyl sulfate (SDS), and phorbol myristate acetate (PMA). AB - The phorbol myristate acetate (PMA) stimulation of the human neutrophil NADPH oxidase has been demonstrated through the activation of protein kinase C (PK-C), using light membrane fractions from nitrogen-cavitated cells. Both arachidonic acid (AA) and sodium dodecyl sulfate (SDS) can also generate an active oxidase in cellfree systems. That the source of O2- with AA and SDS activation is the same NADPH-oxidase as previously studied was confirmed by the similar pH optima and Km values for NADPH as those previously described for the O2- -generating activity harvested from pre-stimulated human neutrophils. In contrast to the stimulation by PMA, however, the stimulation of the NADPH-oxidase by AA and SDS does not appear to require protein kinase C activation: the action of AA and SDS is independent of the addition of PK-C cofactors to the system, and the inhibitor of PK-C activity, H-7, had no effect on the stimulation by AA or SDS. AA and SDS activation are comparable, but the level of NADPH-oxidase expression is sixfold greater with each of these agents than that obtained with a reconstituted PK-C system. The basis of this difference in oxidase expression is unclear, but these findings suggest strongly that although activated PK-C is capable of stimulating a dormant NADPH-oxidase in a cellfree system, this is not the sole pathway for oxidase activation. PMID- 3102605 TI - Cellular subsets involved in cell-mediated immunity to murine Plasmodium yoelii 17X malaria. AB - Cell mediated immunity to nonlethal Plasmodium yoelli 17X (PY17X-NL) was examined in the CBA/CaJ mouse by adoptive transfer of sensitized T lymphocyte subsets. In intact mice, PY17X-NL causes a self-limiting infection with parasitemia levels ranging from 10 to 25% of total red blood cells. Upon recovery, mice are refractory to subsequent challenge with the homologous parasite. In T cell depleted mice, PY17X-NL infections are extremely virulent and result in death of the host after parasitemia levels reach 50% or higher. The transfer of either Lyt 1 T cells or Lyt-2 T cells from immune animals into normal, naive animals produced accelerated recovery to subsequent infection. However, this adoptive transfer of immunity by either subset was dependent upon the presence of an I-J+, Lyt-null cell in the immune population. T cell deprivation precluded the ability of animals to control blood-stage infections. When T cell-depleted mice were reconstituted with naive, Ig-negative (T cell-enriched) spleen cells, parasitemia levels were controlled and the parasites were eliminated. When T cell-deprived animals were reconstituted with naive Lyt-1+2-, Ig-negative spleen cells, they experienced twofold higher parasitemias of longer duration than mice receiving unfractionated cells. Two of six of these Lyt-1 mice died of fulminant infections, suggesting that the presence of naive Lyt-2 cells enhances the degree of protection. Immune Lyt-2 T cells were highly protective in T cell-depleted animals. Protection by sensitized Lyt-1 T cells correlated with the induction of a monocytosis. On the other hand, protection by Lyt-2T cells occurred in the absence of monocytosis. The possibility that the immunity induced by each T cell subset is mediated by a different effector mechanism is discussed. PMID- 3102606 TI - Effects of interferon-gamma on proto-oncogene expression during induction of human monocytic differentiation. AB - Activation of the proto-oncogenes c-fos, c-fms, and c-sis has been associated with monocytic differentiation. In the present study, we monitored the relationship of c-myc, c-fos, c-fms, and c-sis expression to interferon-gamma (IFN-gamma)-induced monocytic differentiation of human HL-60 promyelocytic leukemia cells. Treatment of HL-60 cells with 500 U/ml IFN-gamma arrested cell proliferation after 3 days. Appearance of the monocytic phenotype was manifested within 24 hr of IFN-gamma exposure by: increased nitroblue tetrazolium reduction; increased cell surface expression of the HLA-DR, Mo1, and MY4 antigens; and induction of transcripts for the second component of complement (C2) and tumor necrosis factor. In contrast, c-myc expression decreased as a later event after 72 hr of IFN-gamma exposure, and c-fos transcripts remained undetectable until 5 days of treatment. Furthermore, c-fms RNA and transcripts for the macrophage marker apolipoprotein E were induced only after 7 days. Finally, expression of the c-sis proto-oncogene at the RNA and protein levels remained undetectable after induction with IFN-gamma. These findings would thus suggest that declines in c-myc RNA, as well as induction of c-fos, c-fms, and c-sis expression, are not requisite events in the commitment of HL-60 cells to IFN-gamma-induced monocytic differentiation. Expression of c-fos and c-fms, however, is associated with acquisition of markers associated with maturation to macrophages. PMID- 3102607 TI - Abnormal expression of T cell receptor genes in Lyt-2- L3T4- lymphocytes of lpr mice: comparison with normal immature thymocytes. AB - The autoimmunity and lymphoproliferation characteristic of lpr mice are age and thymus dependent. The accumulating Lyt-2- L3T4- T cells express only minimal cell surface antigen receptor. After stimulation with phorbol myristic acetate (PMA) and interleukin 2, essentially normal levels of surface antigen receptor were expressed by the lpr Lyt-2- L3T4- subpopulation but remained undetectable in the corresponding normal immature thymocyte population. We have found near normal T cell receptor (TCR)-alpha and -beta mRNA expression by these lpr cells. The phenotypically comparable Lyt-2- L3T4- subset of normal thymocytes expressed approximately 10-fold less TCR-alpha mRNA than normal lymph node cells and somewhat higher TCR-beta mRNA. After cultivation of this immature thymocyte subpopulation with PMA and interleukin 2, TCR-alpha mRNA levels remained low, and TCR-beta transcripts were found to be subnormal. By using the same culture conditions, the corresponding mRNA levels of the lpr subset tended to resemble those of Lyt-2- L3T4- thymocytes. Fresh and cultured Lyt-2- L3T4- normal thymocytes showed comparably high levels of full-length TCR-gamma transcripts. In contrast, the fresh lpr subset had barely detectable levels of TCR-gamma mRNA. Upon cultivation, however, these levels increased over 200-fold to within the range observed in the Lyt-2- L3T4- thymocyte subset. No induction of the gamma gene was observed in similarly cultured normal lymph node T cells. The lpr cells may therefore correspond to an as yet undefined stage of normal T cell differentiation. PMID- 3102608 TI - The gene encoding the mouse T cell differentiation antigen L3T4 is located on chromosome 6. AB - We have used Southern blot analysis of DNA from somatic cell hybrids to map the chromosomal location of the mouse L3T4 T cell differentiation antigen gene to chromosome 6. This finding is of interest because both L3T4 and the alternative T cell differentiation antigen Lyt-2 are homologous to kappa-immunoglobulin light chain-variable regions, and the genes encoding kappa and Lyt-2 are also located on mouse chromosome 6. PMID- 3102609 TI - Anti-tumor activity of class II MHC antigen-restricted cloned autoreactive T cells. I. Destruction of B16 melanoma cells mediated by bystander cytolysis in vitro. AB - Two Lyt-1+, L3T4a+ autoreactive T cell clones specific for self-class II major histocompatibility complex (MHC) gene products were established from lymph node cells and spleen cells of C57BL/6J mice, respectively, by different methods. They were stimulated to proliferate in culture in response to I-Ab antigen-bearing syngeneic spleen cells in a class II MHC-restricted manner. This stimulation was inhibited completely by the addition of anti-L3T4a (GK1.5) or anti-I-Ab (3JP) monoclonal antibodies. The autoreactive T cell clones lysed syngeneic I-Ab+ target cells such as lipopolysaccharide (LPS) blasts. They also lysed I-A- bystander cells such as Cloudman and B16 melanoma and lymphoid tumor cells in the presence of I-Ab+ stimulator cells but not I-Ad+ cells. This bystander killing was most likely mediated by soluble factors released from the autoreactive T cells in response to I-Ab antigens, because culture supernatants from activated autoreactive T cells inhibited the proliferation of B16 melanoma cells in vitro and also had significant cytolytic activity. Both lymphotoxin and interferon gamma were released from activated autoreactive T cells, suggesting that these cytotoxic lymphokines were responsible for autoreactive T cell-mediated cytolysis. The finding that the two clones, established independently and by different methods, show self-class II MHC antigen-restricted cytolysis, and bystander cytolysis suggests that these properties are not restricted to a unique population of autoreactive T cells. These results favor the concept that in vivo, autoreactive T cells may express not only regulatory activity in regard to antibody responses, but also anti-tumor activity via bystander cytolysis. PMID- 3102610 TI - Quantitative measurement of T-lymphocyte activation by an enzyme-linked immunosorbent assay (ELISA) detecting interleukin-2 receptor expression. AB - A monoclonal antibody prepared against the murine interleukin-2 receptor (IL-2R) was employed to develop an ELISA method for measuring the immunological activation of T-cells. The assay detects an increase in IL-2R expression on activated lymphocytes. Stimulated splenic lymphocytes displayed markedly higher IL-2R expression compared to unstimulated controls. A significant increase in IL 2R expression on lymphocytes was detected in mitogen-stimulated responses, in a one-way mixed leukocyte reaction (MLR) and in the antigen-specific responses to conalbumin and purified protein derivative (PPD) in vitro. At a constant cell number, the level of IL-2R expression was found to be dependent on the dose of the stimulant. A comparative study of the kinetics of activation of splenic lymphocytes in response to mitogen, antigen and allogeneic cells as measured by the IL-2R ELISA and the conventional tritiated thymidine (3HTdR) uptake assay revealed remarkable similarity. For both assays, the mitogenic response was detected within 12 h and peaked at 72 h, the MLR was detectable within 2-3 days and peaked at day 6, and the specific antigenic response was detected within 2 days and peaked on day 4-5. Hydroxyurea, an inhibitor of DNA synthesis, had no effect on early IL-2R expression by mitogen-stimulated splenic lymphocytes, however, only 20% of maximum IL-2R expression could be detected at later stages of incubation. In contrast, cycloheximide, an inhibitor of protein synthesis, completely abrogated IL-2R expression and proliferation of stimulated lymphocytes. PMID- 3102611 TI - A sensitive micro-immunoassay using beta-galactosidase/anti-beta-galactosidase complexes. AB - This paper describes a new sensitive microELISA based on enzyme/anti-enzyme complexes following an unlabelled antibody bridging step. beta-Galactosidase/anti beta-galactosidase complexes were made using a monoclonal antibody raised against bacterial (E. coli) beta-galactosidase and enzyme activity was quantified with a fluorogenic substrate. Because of its high sensitivity the assay is particularly suitable for the detection of limited amounts of antigen. One application illustrated is the analysis of Class I and Class II histocompatibility antigens on peripheral blood lymphocytes using 5000 cells/well in 60-well Terasaki or 96 well microtitre plates. PMID- 3102612 TI - Highly sensitive enzyme immunoassays for beta-nerve growth factor. AB - A comparison was made between three different strategies for measuring beta-nerve growth factor (NGF) by fluorometric enzyme immunoassay. The substrate used was 4 methylumbelliferyl-beta-galactoside and the enzyme reaction was followed in a Microfluor plate reader (Dynatech). After optimizing incubation times, concentrations, buffers, pH, and washings, a primary anti-NGF antibody directly conjugated to beta-galactosidase gave the best detection limit (2 X 10(-17) M) of purified mouse NGF (Mr 26,000) in a two-site sandwich assay. Biotinylated secondary antibodies followed by streptavidin conjugated beta-galactosidase proved to be 200-fold less sensitive in a similar assay. Finally, blotting NGF onto nitrocellulose membranes for detection with the same biotin-streptavidin steps after incubation with unlabelled primary antibodies resulted in a detection limit of 3 X 10(-12) M. All three methods indicated the same level (4 X 10(-11) M) of endogenous NGF in the rat brain hippocampus. PMID- 3102613 TI - Solid-phase radioimmunoassay for the measurement of surface antigens expressed on intact lymphocytes. AB - A solid-phase radioimmunoassay was developed for the measurement of lymphocyte surface antigens. The assay was performed in microplates, using cells that were initially fixed to the wells by air drying. The method was used for the measurement of Thy-1, Lyt-1,2,3, IL-2-R, H-2Kb and DR antigens on the surface of mouse thymus, spleen and bone marrow cells, mouse cell lines CTLL, EL-4 and DA-1 and human thymocytes and consisted of sequential incubations with rat or mouse monoclonal antibodies directed against the above antigens, rabbit anti-rat or goat anti-mouse IgG and 125I-protein A. The assay permits the processing of large numbers of samples, is easy to perform, reliable and highly specific. PMID- 3102614 TI - Production of mycoplasma-specific antisera in rabbits immunologically tolerized at birth to mycoplasma medium constituents. AB - Neonatal rabbits were injected intraperitoneally (i.p.) within 12 h of birth followed by similar injections every day for 10 consecutive days and then every second day for a further 8 weeks, with mycoplasma broth medium (tolerogen), to induce immune tolerance. The rabbits were then immunized with the porcine mycoplasmas, M. hyopneumoniae or M. hyorhinis at 9 weeks of age. Immune sera obtained from these rabbits and from normal control rabbits were tested for antibodies against both mycoplasma antigens and for antibodies to medium components by double immunodiffusion in agarose and by enzyme-linked immunosorbent assay (ELISA). Antisera obtained from the tolerized rabbits contained no antibodies to medium components as evidenced by lack of reactivity in both assays. In immunofluorescence tests the antisera obtained from tolerized rabbits permitted specific staining of colonies of the homologous mycoplasma grown on mycoplasma agarose medium. In contrast the antisera obtained from normal rabbits produced strong reactions in all of the tests and non-specific background fluorescence due to reactions with components of the culture medium. PMID- 3102615 TI - Comparison of antigens and antisera in crossed immunoelectrophoresis by dual dilution. AB - The localization of individual precipitates in the crossed immunoelectrophoresis (CIE) pattern is an important feature for their identification, but in a given system this pattern may vary markedly when different antigen preparations or antisera are used. Two different antigen preparations or antisera may be compared by mixing them in various proportions in a set of four CIE plates. The amounts of the preparations to be compared are selected to obtain a gradual change in position of individual precipitates if differences are encountered. Similarities between antigen or antibody preparations are recorded when the positions of precipitates remain unchanged. The technique is particularly valuable for comparing complex patterns with a large number of precipitate lines. PMID- 3102616 TI - A simple method for the production of specific antiserum to protein encoded in cloned genes. Immunization with precipitin lines. AB - A simple technique for raising specific antisera to protein encoded by cloned genes is described. The procedure involves preparation of an antiserum to Escherichia coli beta-galactosidase and the use of that serum to immunoprecipitate a fusion protein in a crossed immunoelectrophoresis gel followed by immunization with fusion protein precipitin arcs. An antiserum was prepared against protein encoded by an open reading frame in a dispersed repeated DNA sequence found in the protozoan Trypanosoma brucei. This serum recognized a polypeptide doublet of 33.5 and 32.5 kDa on immunoblots prepared from extracts of T. brucei. The method described should be applicable to other investigations where an immunochemical reagent against protein encoded by a cloned gene is desired. PMID- 3102617 TI - Differential expression of HLA class I and II antigens in primary and metastatic melanomas. AB - Class I and II histocompatibility antigen expression was studied in cryostat sections of biopsy tissues from 15 patients diagnosed as suffering from malignant melanoma, using monoclonal antibodies against HLA class I and II monomorphic determinants and an indirect immunofluorescence technique. Class I antigens were detected in three of the four primary melanomas and in five of the eleven metastatic melanomas. Class II antigens were expressed only in metastatic melanomas, in three out of eleven cases. Some tumour cell suspensions were obtained and short-term cultures were established. Radiobinding and immunoprecipitation studies were carried out in two cases, named M6 and M8. The results were comparable to those obtained with direct immunofluorescence. We modulated the expression of class I and II HLA antigens with interferon in M6 when adapted to tissue culture. This melanoma was class I and II negative; after IFN gamma treatment it became strongly positive for class I and II antigens. In addition we have demonstrated, using Southern blot analysis with the restriction enzymes PvuII and EcoRI, that the M6 melanoma does not have any detectable alterations in its class II beta genes. PMID- 3102618 TI - Modulation of the expression of HLA class II antigens by gamma interferon and phorbol ester TPA on myeloid leukaemic cell lines. AB - We investigated the effect of gamma interferon and phorbol ester (TPA), on the expression of HLA class II molecules of myeloid leukaemic cell lines K562, U937, KG-1, HL-60 and ML-2. Gamma interferon induced the expression of HLA-DR but not HLA-DQ on HL-60 and ML-2, increased the expression of HLA-DR and DQ on U937 and induced the expression of HLA-DQ on KG-1. TPA treatment did not affect the expression of HLA class II antigens on U937 and KG-1 and induced the expression of HLA-DR and HLA-DQ on HL-60 and ML-2. TPA treatment did not affect the HLA phenotype of K562 but gamma interferon did induce HLA class I molecules. Thus, gamma interferon cannot only increase the expression of HLA products already expressed on the cells but can also induce the de novo synthesis of these molecules on myeloid leukaemic cell lines. PMID- 3102619 TI - [Cancer of the prostate. Results and causes of failure after exclusive radiotherapy in 131 cases treated at in locoregional stage between 1972 and 1981]. AB - A retrospective study was carried out to evaluate results of exclusively physical treatment by external radiotherapy of 131 cases of cancer of prostate treated between 1972 and 1981. Median follow up has been for 8 years in 19 cases (stage A), 61 cases (stage B) and 51 cases (stage C). Patients were treated exclusively by external irradiation after histopathologic diagnosis and assessment of possible extension of tumor. High energy photons were developed by a linear accelerator and irradiation carried out through four portals, two anteroposterior, two lateral, with precise guidance by rectal and bladder opacification. Irradiation delivered to a pelvic volume over 5 weeks was subsequently reduced to the prostate bed until a total dose of about 65 to 70 Gy has been given. Primary glandular chains received 60 to 65 Gy, and critical organs, bladder, rectum, small intestine a smaller dose of less than the tolerance levels for these organs. Clinical, biologic and scintiscan examinations were repeated every three months. Results are presented as actuarial survival, as survival without local recurrence and a detailed analysis of failure of treatment. The 8-year survival rate was 60% for stage A, 47% for stage B and 33% for stage C. Unsuccessful cases were evaluated in terms of isolated metastases, metastases associated with local recurrence and isolated local recurrence. The highest incidence of ineffectiveness of therapy was noted in patients with distant metastases (26%), the rate being higher (41%) in stage C cases than in stage B cases (19%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102620 TI - [Vesicorenal reflux following endoscopic treatment of vesical tumors. Developmental and therapeutic complications]. AB - A survey of 107 patients treated for bladder papillomatosis, 78 of which recurred, confirmed the frequency of appearance of an iatrogenic reflux (28 cases: 26%). The main explanations for its onset are resection and orificial sclerosis. Two consequences of reflux are discussed. One is very probable: the development of tumoral lesions in the upper excretory pathways. Noted in 7 (25%) of the 28 cases, these high tumors can be partly explained by the mechanism of cell implantation, grafts being ascending in cases of reflux. A relation between severity of reflux and site of secondary tumor was not found (6 unilateral and 1 bilateral tumor). This was also true for the effect of the bladder lesion stage on frequency of high localizations. The second possible consequence of reflux, the subject of much greater debate, concerns the increased risk of toxicity from local chemotherapy which could lead to increase in the time and area of contact. This risk appears to be very low (2 interruptions of therapy in 10 patients treated with Thiotepa, none with mitomycin). Diagnosis of reflux affects treatment of the bladder tumor. When reflux is associated with high lesions, treatment of the tumor is the first imperative and is dependent on the manner in which it is conceived. When reflux is isolated, its surgical correction with the aim of preventing development of a pyelo-ureteral tumor is not widely accepted, since the condition of the patient and the course of the bladder disease must be taken into consideration. PMID- 3102621 TI - Differential effects of protoporphyrin and uroporphyrin on murine mast cells. AB - To investigate the mechanisms responsible for the distinct cutaneous manifestations of erythropoietic protoporphyria and porphyria cutanea tarda, the effects of protoporphyrin (PP) and uroporphyrin (URO), the predominant porphyrins in the respective disease, on mast cells were examined. Release of preformed and generated mediators was assessed by the release of radioactivity from cells labeled with [3H]serotonin and [14C]arachidonic acid, respectively. Clinically relevant doses of PP (25-500 ng/ml) and 396-407 nm irradiation (3-16 X 10(2)J/m2) induced maximal net release of preformed mediators of 44.52 +/- 6.6 to 58.01 +/- 4.0% (mean +/- SE). In contrast, irradiation in the presence of URO (50-5000 ng/ml) resulted in less than 5% net release. [3H]Serotonin release induced by PP and irradiation was calcium-independent, and was not enhanced by phorbol 12 myristate 13-acetate, a known activator of protein kinase C. This release was suppressed by catalase, a scavenger of hydrogen peroxide. Furthermore, irradiation in the presence of PP, but not in the presence of URO, resulted in perturbation of cell membrane. Irradiation in the presence of PP also resulted in a maximal net release of generated mediators of 9.98 +/- 3.5% (mean +/- SE), whereas similar treatment in the presence of URO induced less than 0.5% net release. These results suggested that the burning, stinging, erythema, and edema experienced by patients with erythropoietic protoporphyria following sun exposure, and the lack of such findings in patients with porphyria cutanea tarda, may be explained, at least in part, by the differential effects of PP and URO on mast cells. PMID- 3102622 TI - A computed image analyzing system for quantitation of melanocyte morphology in cafe-au-lait macules of neurofibromatosis. AB - Split-dopa preparation is a commonly used technique to visualize the epidermal melanocytes. It can characterize the number of melanocytes and their tyrosinase (dopa-oxidase) activities. There is not, however, any method to quantitate the morphologic changes of dopa-positive melanocytes in the split preparation. This study designed a computed image analyzing system and evaluated the structure of epidermal melanocytes in cafe-au-lait macules with comparison to normally pigmented skin in 5 patients with neurofibromatosis. By this method we were able to delineate the melanocyte structure with melanocyte population and coloration of the macules. We found that the population and structure of melanocytes differ greatly depending on the coloration of the cafe-au-lait macules. The light brown and brown macules showed the normal population of melanocytes with an increase in the area and perimeter of whole cell; the area, perimeter, and diameter of cytoplasm; and the area, length, and breadth of dendrites. In contrast, the dark brown macules revealed a significant increase of the epidermal melanocytes with a decrease in all of these parameters. Thus, the methodologic design presented here may enable a quantitative, two-dimensional analysis of melanocyte structure at the light microscopic level in the normal skin and in various pigmentary disorders. PMID- 3102623 TI - Tyrosinase and acid phosphatase activities in melanocytes from avian albinos. AB - Two forms of cutaneous albinism in the chicken were investigated for the presence and distribution of tyrosinase and acid phosphatase in melanocytes in situ and in culture. In sex-linked recessive tyrosinase-positive albinism, sal, melanocytes in regenerating feathers and neural tube-derived cultures contained morphologically normal and abnormal premelanosomes. Tyrosinase was localized primarily to the abnormal premelanosomes and probably not to the normal ones. The cells possessed, in addition, vacuoles with membranous inclusions, located in the dendrites, and capped by dopa-positive vesicles (capping vesicles). Acid phosphatase colocalized with tyrosinase in the abnormal premelanosomes and capping vesicles. Tyrosinase activity in extracts of cultured sal melanocytes equalled that of e+ control melanocytes. A tyrosinase antiserum, raised against hamster tyrosinase (Pomerantz), precipitated 2 proteins, 68 kD and 82 kD, which had a precursor-product relationship. The amount of immunoprecipitate was the same in sal and control extracts, but in sal extracts the lower-molecular-weight protein was twice as abundant as the higher-molecular-weight protein. Melanocytes in regenerating feathers from an autosomal recessive, tyrosinase-negative albino, ca, also contained morphologically normal and abnormal premelanosomes. In culture, ca melanocytes had no formal premelanosomes but only dopa-negative multivesicular bodies with wispy filamentous material. Tyrosinase activity and immunoprecipitable tyrosinase were absent. These results suggest that: the tyrosinase-positive albino, sal, has an aberration in both its tyrosinase and acid phosphatase profiles and the tyrosinase-negative albino, ca, lacks functionally and antigenically normal tyrosinase. PMID- 3102624 TI - Human dermal microvascular endothelial cells behave like umbilical vein endothelial cells in T-cell adhesion studies. AB - The adhesion of T lymphocytes to human dermal microvascular endothelial cells (DMVEC) in vitro has been tested after stimulation of the DMVEC with gamma interferon (IFN-gamma), interleukin 1 (IL-1), or a bacterial lipopolysaccharide (LPS). These agents enhanced T-cell adhesion in a manner similar to that previously observed with human umbilical vein endothelial cells (UVEC). Moreover, phorbol ester stimulation of T cells enhanced T-cell adhesion to both DMVEC and UVEC. Unstimulated and phorbol ester-enhanced T-cell adhesion to both DMVEC and UVEC was strongly inhibited by monoclonal antibody (Mab) 60.3 against the surface membrane CDw18 glycoprotein complex. In contrast, Mab 60.3 had a much weaker inhibitory effect on the binding enhancement due to IL-1, LPS, or IFN-gamma, suggesting that these agents may enhance adhesion by a mechanism at least partially independent of CDw18. These observations suggest that DMVEC behave in a similar fashion to UVEC in T-cell adhesion studies, and support previous conclusions that modulation of lymphocyte endothelial cell adhesion by cytokines, bacterial products, and phorbol esters may be relevant to lymphocyte adhesion and migration in vivo. PMID- 3102625 TI - Skin microflora. PMID- 3102626 TI - New approaches to the rapid diagnosis of tuberculous meningitis. PMID- 3102627 TI - Activity of adenosine deaminase in cerebrospinal fluid for the diagnosis and follow-up of tuberculous meningitis in adults. AB - We studied the activity of adenosine deaminase in the cerebrospinal fluid of 40 normal controls and 205 patients who were grouped according to disease (tuberculous, viral, and purulent meningitis; neoplasms; stroke; and miscellaneous). The mean enzyme value was clearly higher for the patients with tuberculous meningitis (15.7 +/- 4.3 U/liter) than for the other patients (1.4 +/ 1.5 U/liter). The sensitivity of the test for diagnosing tuberculous meningitis was 1 and specificity, 0.99. The enzyme activity, as well as progression of the disease, was studied in 32 patients with tuberculous meningitis. A significant rise in levels of enzyme was observed during the first 10 days of therapy, was followed by a gradual decline, and reached normal values after three to four months of treatment. Two patients showed substantial increases that coincided with the development of complications. The test proved to be a simple and reliable method for early diagnosis and follow-up of tuberculous meningitis. PMID- 3102628 TI - Radioimmunoassay for detecting Mycobacterium tuberculosis antigen in cerebrospinal fluids of patients with tuberculous meningitis. AB - A biotin-avidin radioimmunoassay for detecting Mycobacterium tuberculosis antigen has been developed. The assay involves sandwiching mycobacterial antigens from sonicate preparations and cerebrospinal fluids between two antibodies produced in burros and rabbits. The reaction is amplified by using biotinylated antibody to rabbit IgG and 125I-labeled avidin. The assay has a sensitivity of 20 ng/ml and shows less than 5% cross-reactivity with six other mycobacteria. We studied patients with untreated tuberculous meningitis, patients with treated tuberculous meningitis, patients with nonbacterial meningitis, and patients with bacterial meningitis. Antigen was detectable in two of 56 control samples (40 ng/ml). Hence, samples with greater than or equal to 80 ng of antigen/ml were considered positive. In patients with untreated tuberculous meningitis, antigen levels ranged from 20 to 10,000 ng/ml, and 15 (79%) of 19 samples were positive. In the treated group, only two (10%) of 17 samples were positive. This test promises to be a rapid adjunct in the early diagnosis of tuberculous meningitis. PMID- 3102629 TI - Mesenchymal target cell specificity of egg granuloma-derived fibroblast growth factor in schistosomiasis. AB - We previously demonstrated that egg granulomas isolated from the liver of mice infected with Schistosoma mansoni secrete factors that stimulate fibroblast proliferation in vitro. Because this growth factor also stimulated thymocyte proliferation, we further investigated the mesenchymal target cell specificity of this factor. We now report that granulomas also secrete material that promotes growth of aortic smooth muscle and endothelial cells. We found that the activities that stimulate fibroblast and smooth muscle cell growth share similar physicochemical properties (Mr, 30-40 kilodaltons [kDa]; pI, approximately 6.5), a result suggesting that they are the same or related molecules. In contrast, fractions (Mr, less than 10 kDa; pI, 6.7-7.5) that maximally stimulated endothelial cells had minimal or no effects on the other two cell types. We postulate that soluble granuloma products might also stimulate in vivo proliferation of vascular smooth muscle and endothelial cells and contribute to the pathology of the intrahepatic vessels in schistosomiasis. PMID- 3102630 TI - Beta-lactamase lability and inducer power of newer beta-lactam antibiotics in relation to their activity against beta-lactamase-inducibility mutants of Pseudomonas aeruginosa. AB - The interactions of imipenem, carbenicillin, cefotaxime, ceftriaxone, and azlocillin with the chromosomal beta-lactamase of Pseudomonas aeruginosa were compared. Imipenem was hydrolyzed very slowly (kcat, 1/min) and induced beta lactamase synthesis strongly. Its minimal inhibitory concentrations (MICs) reflected this behavior, being equal (1-2 micrograms/ml) for enzyme-inducible strains and their stably derepressed mutants. Mutants that had basal (i.e., minimal and uninducible) enzyme production were eight- to 16-fold more susceptible to imipenem than were inducible or stably derepressed strains. Carbenicillin was stable to hydrolysis (kcat, less than 0.1/min) and induced weakly at low concentrations. Consequently its MICs were equal for beta-lactamase inducible strains and for their basal mutants. Stable beta-lactamase derepression generally did not increase resistance to carbenicillin significantly. Azlocillin, cefotaxime, and ceftriaxone were labile to hydrolysis (kcat, 12-297/min) but induced poorly. Consequently their MICs for enzyme-inducible strains equaled those for basal mutants but were elevated for derepressed mutants. PMID- 3102631 TI - Comparative efficacy of ciprofloxacin, azlocillin, and tobramycin alone and in combination in experimental Pseudomonas sepsis. AB - Ciprofloxacin, azlocillin, and tobramycin, used alone and in combination, were studied in a model of lethal pseudomonas sepsis in rats. Ciprofloxacin alone at all doses studied and tobramycin alone at the highest dose reduced mortality significantly compared with saline controls. In contrast, survival was not improved with either azlocillin alone at all doses studied or lower doses of tobramycin alone. The combination of ciprofloxacin and azlocillin was synergistic in rats with systemic pseudomonas infection. Ciprofloxacin was rapidly absorbed, and effective levels persisted for 1-4 hr relative to the dose administered. These data suggest that ciprofloxacin may be a potent agent, either alone or in combination with azlocillin, in the treatment of severe pseudomonas infections. PMID- 3102632 TI - In vitro effect of cyclosporine on interleukin-2 receptor expression stimulated by Cryptococcus neoformans. PMID- 3102633 TI - Interaction of magnesium ion, oxygen tension, and temperature in the production of toxic-shock-syndrome toxin-1 by Staphylococcus aureus. PMID- 3102634 TI - Meningitis caused by a nonencapsulated strain of Neisseria meningitidis in twin infants with a C6 deficiency. PMID- 3102635 TI - Frequency and distribution in the United States of strains of Neisseria gonorrhoeae with plasmid-mediated, high-level resistance to tetracycline. PMID- 3102636 TI - Ofloxacin therapy for experimental osteomyelitis caused by Pseudomonas aeruginosa. PMID- 3102637 TI - [Experimental Pseudomonas pneumonia model in normal mice]. PMID- 3102638 TI - [An analysis of 147 patients with septicemia at the Department of Internal Medicine of Yamaguchi Prefectural Central Hospital for 16 years (1968-1983). III. Clinical study of patients with septicemia due to rare organisms]. PMID- 3102639 TI - [Antibody titers in the serum of patients vaccinated with the multicomponent vaccine consisting of toxoids of protease, elastase and a common protective antigen (OEP)]. PMID- 3102641 TI - [Fundamental and clinical studies on intravenous drip infusion of HAPA-B. Intravenous Drip Infusion HAPA-B research Group]. PMID- 3102640 TI - [Comparison of HAPA-B and amikacin in the treatment of respiratory tract infections]. PMID- 3102642 TI - [Detection of Chlamydia trachomatis from female genital tracts by the Micro Trak method]. PMID- 3102643 TI - [A case of pseudomembranous colitis developing after ticarcillin therapy]. PMID- 3102644 TI - [Two cases of chronic Schistosomiasis japonica contracted in the Tone River Basin of Saitama Prefecture]. PMID- 3102645 TI - [Changes in the lymphocyte count in tsutsugamushi fever]. PMID- 3102646 TI - [Superovulation-induced transient hyperprolactinemia in human in vitro fertilization and embryo transfer]. AB - To examine the effects of transient hyperprolactinemia on in vitro fertilization and embryo transfer, 61 cycles in 50 euprolactinemic ovulatory women with irreparable tubal diseases were stimulated with clomiphene (CC) alone or CC and human menopausal gonadotropin followed by human chorionic gonadotropin (hCG). Serum prolactin (PRL) increased after hCG administration with peak values of 45.4 +/- 4.2 ng/ml on the day of laparoscopic oocyte aspiration. The highest serum estradiol (E2) concentration was found on the day before PRL peak and serum progesterone (P) began to increase after hCG injection concomitant with the PRL rise. The group having 50 ng/ml or more of PRL (34 cycles) had significantly higher levels of E2 during preovulatory and early luteal phase compared to those of the group having less than 50 ng/ml of PRL (27 cycles) but there was no significant difference between the P levels in the two groups. In the higher PRL group 72 (62.1%) of 116 collected oocytes were fertilized and 6 (20.0%) conceived. In the lower PRL group 45 oocytes (58.4%) of 77 were fertilized and 3 (12.5%) became pregnant. These data suggest that elevated serum PRL concentrations may have no effect on fertilization of oocytes in vitro or embryonic development. PMID- 3102647 TI - [Effects of acid-base balance and Apgar score on fibrinopeptide A and fibrinopeptide B beta 15-42 in umbilical cord blood]. AB - Previous studies on asphyxia neonatorum show that the infant's blood is in a state of hypercoagulability at such a time. In the present study, we determined the amount of fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta), new sensitive indicators of the coagulation-fibrinolytic system, in the newborn, and examined their relationship to the acid-base balance in umbilical artery blood in elective cesarean section and vaginal delivery, as well as to the Apgar score (Ap. S). In addition, the findings in umbilical cord blood were then compared with those in the blood of normal adults. The results were as follows: In vaginal delivery, infants with Ap. S at 5-7, pH, had significantly lower HCO-3 and BE readings lower while PCO2 was significantly increased, which indicated respiratory and metabolic acidosis. In the vaginal delivery group, FPA was significantly increased in infants with pH under 7.24, PCO2 over 50 mmHg, BE under -8 and Ap. S at 5-7, and as well as in infants in the elective cesarean section group with Ap. S at 5-7. This suggests that the production of thrombin is accelerated if the fetus is asphyxiated. FPB beta was not significantly different among groups. However, FPB beta was significantly higher in various vaginal delivery groups than in the elective cesarean section group (Ap. S greater than or equal to 8), which implies acceleration of the production of plasmin and fibrinolysis in vaginal delivery. FPA and FPB beta were markedly increased in umbilical cord blood as compared with the blood of normal adults. This suggests that blood coagulation and fibrinolysis were accelerated in umbilical cord blood. PMID- 3102648 TI - [Experimental studies on the antitumor effect of oral antitumor agents on gynecological malignant tumors]. AB - In order to evaluate the antitumor effect of oral antitumor agents on gynecological malignant tumors, experimental studies were carried out using nude mice which had received implants of human endometrial carcinoma. The agents used for the study were tegafur (T) and UFT, and their effects on inhibiting tumor growth, and on preventing tumors from implanting or recurring were investigated in mice in continuous long-term administrations. The results were as follows: As to the inhibitory effect on the tumor growth, while both T and UFT had no inhibitory effect on large to medium tumors, both were mildly effective on small tumors having a diameter of 2-3 mm (Inhibition Rate (IR): T-60.0%, UFT-71.0%), however, the no effect great enough to reduce the tumor size was recognized with either agent. The implantation rates of tumor under the administration of T and UFT were 80.0% and 70.0% respectively, indicating no significant differences from the control (90.0%) and either agent, however, UFT was judged to have the effect of preventing tumors from implanting to a certain extent. The recurrence rates for tumor under the administration of T and UFT were 30.0% (6/20) in both cases, which was significantly lower than the control (70.0%) (p less than 0.05). Both agents were evaluated as useful for preventing tumors from recurring. These findings, indicated that while the maintenance therapy of an oral antitumor agent has no effect on macroscopic tumors, a fairly good effect is expected on microscopic tumors, especially on the prevention of tumor recurrence. PMID- 3102649 TI - [Hormonal changes during continuous exercise in athletic women]. AB - Recently, the number of women who participate in strenuous exercise has increased significantly. The relationship between delayed menarche and early onset of sports training, and increased incidence of menstrual dysfunction related to athletic activity had led to increased interest. Five basketball players who are among the best players in Japan were subjected to an investigation of endocrinological responses effected by 60 minutes continuous exercise cycle ergometer. The VO2max value was previously examined. Then, the level of load during exercise was established at 60% VO2max in this study. The serum level of estradiol increased significantly in the luteal phase but not so significantly in the follicular phase. Progesterone did not show a significant change during exercise. FSH increased slightly in both phases. However, LH showed a slight increase in the follicular phase and a slight decrease in the luteal phase. On the other hand, prolactin showed a continuous significant increase during exercise in both phases. These data suggested that strenuous daily training leads to a frequent significant increase in prolactin in athletic women and this frequent increase in prolactin may be one of the major factors causing menstrual dysfunction in athletic women. The specialized physician should be more concerned about the managing of athletes who are suffering from menstrual dysfunction. PMID- 3102650 TI - [The effect of inorganic mercury on placental amino acid transport using microvillous membrane vesicles]. AB - To study the toxic effect of inorganic mercury on the placenta we elucidate the effect of inorganic mercury on placental amino acid transport using microvillous membrane vesicles isolated from human normal full term placenta. The transport of amino acids into microvillous membrane vesicles was studied by a rapid filtration technique using a millipore filter. The transport of L-alanine across placental microvillous membrane was Na+ electrochemical gradient dependent and 0.1 mM inorganic mercury inhibited 77% of this Na+ dependent L-alanine transport and 1 mM inorganic mercury inhibits 90% of this Na+ dependent L-alanine transport. The transport of L-lysine across microvillous membrane vesicles was sodium independent and 0.1 mM inorganic mercury inhibited 34% of this transport and 1 mM inorganic mercury inhibited 50% of this transport. These results indicated that one of the toxic effects of inorganic mercury on placenta-fetus unit was the inhibition of placental nutrient transport. PMID- 3102651 TI - [Sister chromatid exchange (SCE) in lymphocytes of patients with cancer of the cervix uteri]. AB - The frequency of spontaneous and Mitomycin C (MMC)-induced sister chromatid exchange (SCE) was investigated in peripheral lymphocytes of 31 untreated patients with cervical cancer (stage 0:7 cases, stage I:9 cases, stage II:6 cases and stage III:9 cases), as well as of 7 untreated patients with myoma uteri and 16 healthy women. Factors affecting SCE frequency were also investigated. Age, smoking and atomic bomb exposure did not influence SCE frequency. However, a family history of cancer significantly increased MMC-induced SCE frequency in the cancer group. The mean spontaneous SCE frequency in the cancer group (9.83 +/- 1.74) was significantly higher than that in the myoma group (8.13 +/- 0.81) and healthy women (7.59 +/- 0.85). The mitomycin C-induced SCE frequency was also higher in the cancer group. Spontaneous and MMC-induced SCE frequency gradually increased with the progression of cervical cancer. All chromosome groups equally contributed to the increased SCE frequency in the cancer group. These results suggest that deoxyribonucleic acid of all chromosomes is damaged in patients with cervical cancer. PMID- 3102652 TI - Efficacy of anticancer agents in vitro and in vivo using cultured human endometrial carcinoma cells--study of therapeutic index. AB - Employing the new cell line, NUE-1, which was derived from cells of ascites in a woman with endometrial carcinoma, the sensitivity test for anticancer agents was carried out in culture and xenografts in nude mice. Anticancer activity in vitro was evaluated by counting surviving cells, and the therapeutic index was expressed by LD50 for mice/MLD90 in vitro. NUE-1 cells were inoculated subcutaneously in BALB/c nude mice, and then tumors serially transplanted were used as materials. Anticancer agents (ADM, CDDP, CHA3, CQ, MMC) at 1/3 LD50 dosage for mice were administered intraperitoneally on a schedule of 3 doses for every 4 days. The results were as follows: The therapeutic index of ADM was highest at five to nineteen times the others In vivo, ADM demonstrated + activity, whereas others had no significant effect There was a close correlation between the therapeutic index and in vivo anticancer effect using nude mice. PMID- 3102653 TI - An epidemiological survey on ossification of ligaments in the cervical and thoracic spine in individuals over 50 years of age. AB - An epidemiological survey on ossification of the spinal ligaments was performed on a total of 1,058 subjects over the age of 50 years by means of roentgenography of the cervical and thoracic spine. Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine was detected in 34 subjects (3.2%) with a predilection for men, whereas OPLL in the thoracic spine was found in 8 (0.8%). There were 325 cases (30.7%) of ossification of the anterior longitudinal ligament (OALL) of stage II or above by Forestier's classification in the region from the cervical to thoracic vertebrae, and these cases included a significantly greater number of men. Ossification of the ligamenta flava (OLF) was observed in 48 cases (4.5%). As for the coexistence of ossification of these ligaments, 364 individuals (34.4%) had at least one instance of OPLL and OALL (stage II or above) in the region from the cervical to thoracic spine, and OLF in the thoracic spine. PMID- 3102654 TI - [A new anti-cancer agent K-18 (conjugate of human IgG and melphalan). (II). Its inhibitory effects on in vitro DNA synthesis of human tumor cells]. PMID- 3102655 TI - Selective induction of hormone-dependent mammary adenocarcinoma in the rat. PMID- 3102656 TI - Laboratory models of breast cancer to aid the elucidation of antiestrogen action. AB - The historical development of carcinogen-induced rat mammary tumors is reviewed. Most work has been done with the polycyclic hydrocarbon dimethylbenz[a]anthracene (DMBA). Huggins was the first to describe a protocol for the routine production of DMBA-induced mammary tumors and demonstrated their ovarian dependency. Pearson found that DMBA-induced tumors could not grow during estrogen administration in hypophysectomized rats, and it was subsequently shown that estrogen-stimulated prolactin release is responsible for tumor growth. The antiestrogen tamoxifen has been used in the treatment of breast cancer and has been studied extensively in the DMBA-induced rat mammary carcinoma model. The complexities of tamoxifen's pharmacology in vivo suggested that the development of estrogen-responsive systems in vitro might facilitate an understanding of tamoxifen's mode of action. The description of estrogen-stimulated prolactin synthesis by primary culture of pituitary gland cells provided an opportunity to study the structure-activity relationships of antiestrogens. A model ("crocodile model") to describe the interaction of estrogens and antiestrogens is proposed. An estrogen will permit the conformation change in the receptor that is necessary to translate into prolactin synthesis. An antiestrogen wedges into the binding site on the receptor to prevent changes in protein conformation. As a result prolactin synthesis is inhibited. An extensive study of structure-activity relationships has been used to describe the nature of the ligand binding site of the estrogen receptor. The model can be used to predict the pharmacology of new agents. PMID- 3102657 TI - Thyrotropin-releasing hormone and thyrotropin secretion. AB - Thyrotropin (TSH) secretion is regulated primarily by thyroid hormones and thyrotropin-releasing hormone (TRH). Normally, TSH secretion is exquisitely sensitive to small increases and decreases in serum thyroid hormone concentrations when they occur as a result of alterations in thyroid secretion. Serum TSH responses to TRH are altered by even smaller decreases and increases in serum thyroid hormone concentrations. This sensitivity explains the value of measurements of basal serum TSH concentrations and serum TSH responses to TRH in the diagnosis of hypothyroidism and hyperthyroidism, respectively. How TRH secretion is regulated is unknown, but the direct inhibitory effect of thyroid hormones on the thyrotrophs minimizes the stimulatory effect of any chronic changes in TRH secretion that may occur. In patients with nonthyroid illness, however, the normal relationships between serum thyroxine and triiodothyronine concentrations and TSH secretion are altered. Slightly or moderately ill patients have decreases in extrathyroidal triiodothyronine production that are not followed by an increase in TSH secretion, although the sensitivity of the thyrotrophs to further reduction or to an increase in triiodothyronine concentration is maintained. More severe illness may result in impaired TSH secretion and thus in decreased thyroidal as well as decreased extrathyroidal thyroid hormone production. These alterations in thyrotroph sensitivity and secretion, so that TSH secretion is not increased when extrathyroidal triiodothyronine production is decreased and thyroid secretion is decreased in more severe illness, suggest that decreased thyroid hormone production is a beneficial adaptation to nonthyroid illness. PMID- 3102658 TI - Value of growth hormone dynamics and somatomedin C (insulin-like growth factor I) levels in predicting the long-term benefit after transsphenoidal surgery for acromegaly. AB - Transsphenoidal microsurgery has been shown to be effective in the management of human growth hormone (hGH)-secreting pituitary adenomas. We have previously demonstrated the usefulness of hGH dynamic testing (oral glucose tolerance, insulin hypoglycemia, and thyrotropin-releasing hormone stimulation test) in evaluating the completeness of removal of the adenomas. In patients with acromegaly, serum insulin-like growth factor I (IGF-I) levels are known to correlate with the activity of the disease. We studied the dynamics of hGH secretion in 43 patients with hGH-secreting adenomas 2 to 3 months after surgery. In addition, serum IGF-I levels were recently measured in frozen sera obtained from these patients at the time of dynamic testing. Of the 43 patients undergoing surgery, 19 had normal basal hGH levels as well as dynamics (group I). Two additional patients had low or undetectable hGH levels and were hypopituitary (group II). These 21 patients were considered cured and had no evidence for recurrence of their disease during a mean follow-up period of 97 months. Serum IGF-I levels were normal in 19 (group I) and low in the remaining two patients (group II). Nine additional patients had normal basal hGH levels but abnormal dynamics of secretion (group III). Serum IGF-I levels were normal postoperatively in seven of eight patients tested in this group. During the follow-up period in these nine patients (group III), biochemical and clinical recurrence of acromegaly developed in five. The remaining 13 patients had persistent elevation of basal hGH levels, and all samples tested (n = 8) had elevated IGF-I levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102659 TI - Erythropoietin titers in anemic, nonuremic patients. AB - Erythropoietin titers when related to the hematocrit percentage and measured by bioassay in 33 normal volunteers and in 61 patients with anemias not complicated by renal or chronic disease were found to overlap with titers measured by radioimmunoassay in 20 normals and 28 patients with similar anemias. Erythropoietin titers measured by radioimmunoassay in 34 patients with rheumatoid arthritis, 25 patients with sickle cell anemia (58 separate samples), and 28 patients with erythroid hypoplasia caused by hematologic malignancies were compared with those in the control group of patients with uncomplicated anemias and found not to differ significantly from titers in this group. Erythropoietin titers measured by bioassay in 12 patients with aplastic anemia also fell within the range of those in the control group. Consequently, erythropoietin titers in these anemias appear to be determined primarily by the degree of anemia and not by any specific effect of these illnesses on the production of erythropoietin. PMID- 3102660 TI - Increased synthesis of elastin in amiodarone-induced pulmonary fibrosis. AB - Both synthesis and total content of lung elastin were measured after induction of interstitial pulmonary fibrosis in hamsters by a single intratracheal insufflation of amiodarone. Elastin synthesis, as measured by 14C-lysine incorporation into desmosine and isodesmosine, was significantly elevated (P less than 0.05) above control values for a 3-week interval after induction of lung injury. Total lung elastin content in the amiodarone-treated animals was 32% greater than in controls (P less than 0.05) 2 weeks after insufflation of the agent. Furthermore, the time course of elastin synthesis in this experimental model was similar to that observed in bleomycin-induced pulmonary fibrosis in hamsters. Increases in elastin may therefore be a common feature of interstitial pulmonary fibrosis and may contribute to the altered lung mechanics seen in this disease. PMID- 3102661 TI - Effect of protein depletion and short-term parenteral refeeding on the host response to interleukin 1 administration. AB - Previous studies have demonstrated that protein malnutrition adversely affects the synthesis and release of interleukin 1 by monocytic cells. The purpose of this study was to investigate the protein and trace metal metabolism of severely protein-malnourished guinea pigs given exogenous interleukin 1 in the postabsorptive state or while concomitantly receiving total parenteral nutrition (TPN). Protein-depleted guinea pigs in the postabsorptive state failed to exhibit fever, granulocytosis, accelerated amino acid oxidation, or an acute-phase protein response after administration of interleukin 1 or endotoxin. However, a reduction in the serum concentration of zinc (P less than 0.05) and iron (P less than 0.05) was observed in the guinea pigs given interleukin 1, but not in those given endotoxin. The short-term (1 day) administration of TPN restored positive leucine balance (P less than 0.001) and reduced leucine release from protein breakdown (P less than 0.001). No other differences in the protein metabolism or trace metal response to interleukin 1 were observed as a result of short-term TPN feeding. Body temperatures of these malnourished guinea pigs given interleukin 1 and TPN became febrile or hypothermic depending on initial body temperatures. It is concluded that an attenuated capacity to synthesize interleukin 1 and a failure to mount an appropriate acute-phase protein response to exogenously administered interleukin 1 exist in this protein-malnourished animal model. Furthermore, this diminished protein response appears to be independent of short term substrate provision because TPN for 1 day was unable to restore the full effects of the acute-phase response as mediated by interleukin 1. PMID- 3102662 TI - Changes in plasma concentrations of LH, FSH and prolactin in ewes receiving melatonin and short-photoperiod treatments to induce early onset of breeding activity. AB - Breeding activity was similarly advanced in ewes given continuous (s.c. implant) or timed (oral dose at 15.30 h) melatonin treatments or subjected to a short (8 h light: 16 h darkness) artificial photoperiod. Treatments commenced in mid-June and were terminated in mid-November. Weekly and serial blood samples were collected before and after treatments commenced, to ascertain the effects on plasma prolactin, LH and FSH concentrations. In addition, serial blood samples were collected for 24 h plasma prolactin and melatonin estimations before and after cessation of the treatments. Plasma prolactin levels were significantly reduced immediately following the start of the melatonin (implant and oral) and short-photoperiod treatments but 'rebounded' to levels greater than control values. The normal seasonal (spring) rise in plasma prolactin was noted in the following year. Before the onset of breeding activity, mean plasma LH and FSH concentrations and LH pulse frequency did not change following any of the treatments. The 24-h plasma melatonin profile accurately reflected the various applied treatments but had re-entrained to the prevailing (natural) photoperiod 1 week after termination of the treatments. There were no significant group differences in 24-h plasma prolactin levels 1 week before or 1 and 11 weeks after the treatments had ceased. Such treatments, although successfully advancing the onset of breeding activity and modifying the seasonal plasma prolactin rhythm, were not manifested through any apparent change in peripheral LH or FSH. PMID- 3102663 TI - Interference of dimethyl alpha-(dimethoxyphosphinyl) p-chlorobenzyl phosphate (SR 202) in thyroid hormone metabolism: evidence of inhibition of monodeiodination. AB - SR-202 is a non-iodinated potential lipid-altering agent. When administered (100 mg) three times per day for 3 days to six euthyroid subjects it was associated with a 30 +/- 3% (mean +/- S.E.M.) fall in 3,3',5-triiodothyronine (T3) (P less than 0.001), a reciprocal 104 +/- 14% rise in 3,3',5'-tri-iodothyronine (reverse T3, rT3) (P less than 0.01), and a 37 +/- 7% rise in thyroxine (T4) (P less than 0.001). Basal and TRH-stimulated TSH did not change. These results suggested that SR-202 was acting as an inhibitor of the peripheral monodeiodination of T4 to T3. During a second study the same subjects received the same dose of SR-202 for a further 3 days following 15 days of progressive substitutive treatment with L-T4, which they continued to take at 200 micrograms/day until the end of the study. Despite higher levels of thyroid hormones in the substituted subjects, similar results were observed, serum T3 falling by 40 +/- 2% (P less than 0.001), serum rT3 and T4 rising by 168 +/- 24% (P less than 0.01) and 37 +/- 9% (P less than 0.01) respectively. These changes provide compelling evidence that SR-202 is an inhibitor of the peripheral conversion of T4 to T3 that acts on thyroid hormone metabolism without provoking a counter-regulatory pituitary response. It might prove to be a useful tool for the clinical investigation of thyroid function. PMID- 3102664 TI - Blockade of the final phase of ovulation has no effect on the post-ovulatory surge of serum FSH in the rabbit. AB - Mating induces a surge of both LH and FSH in the blood of female rabbits, followed 10-12 h later by a surge of FSH only, which begins at the time of ovulation. We have studied the effect of suppression of ovulation on the post ovulatory surge of FSH. In the first experiment, follicular fluid and oocytes were withdrawn from the largest follicles 8 h after coitus. In the second experiment, ovulation was inhibited by injecting the rabbits with 25 mg indomethacin/kg body weight 7.5 h after mating. Levels of serum FSH and LH were measured for 24-48 h after mating. Control rabbits ovulated normally in both experiments. The treatments did not significantly affect the levels of serum FSH in either experiment, although the second surge of FSH was slightly higher after fluid had been aspirated from the preovulatory follicles. These observations show that the post-ovulatory surge of serum FSH is not dependent upon the completion of ovulation and that it is programmed before 7.5-8 h post coitum. PMID- 3102665 TI - Neuroendocrine studies in hyperprolactinaemic male mice. AB - In several species, including man and the rat, hyperprolactinaemia is associated with suppression of gonadotrophin release and male sexual behaviour. However, in the hyperprolactinaemic male mouse, plasma LH and FSH levels and copulatory behaviour are increased rather than suppressed. In an attempt to identify mechanism(s) which may be responsible for these effects of hyperprolactinaemia in the mouse, we have examined the effects of two ectopic pituitary isografts on several indices of hypothalamic and pituitary function in adult DBA/2J males. Animals with pituitary grafts had markedly increased plasma concentrations of prolactin, LH and FSH and enlarged seminal vesicles, whereas testicular and pituitary weights were not affected. Content of LHRH receptors and activity of aromatase in the pituitary, as well as dopamine-beta-hydroxylase activity in the hypothalamus were nearly identical in pituitary-grafted and sham-operated males. Biosynthesis of dopamine and turnover of noradrenaline in the median eminence were significantly increased in grafted males. We suggest that the increase in the activity of hypothalamic noradrenergic neurones may mediate stimulatory action of hyperprolactinaemia on LH and FSH release in the mouse. Comparison of these results with those obtained previously in the rat suggests that species differences in the effects of prolactin on gonadotrophin release may be related to its divergent effects on noradrenaline turnover. PMID- 3102666 TI - Oestrogen receptor in the granulosa cell during postnatal development of the rat ovary. AB - Numbers of granulosa cells obtained from follicles of immature rats increased from 1.6 X 10(5) cells/ovary on day 8 to 7.1 X 10(6) cells/ovary on day 40 of age, the day of vaginal opening and first pro-oestrus. Very high levels of cytosol oestrogen receptor were found on day 8 (175,000 sites/cell) but by day 19 20,000 sites/cell were found. Nuclear receptor concentrations were highest on day 12 (5400 +/- 1470 (S.D.)sites/cell) and again on day 21 (5400 +/- 2300 sites/cell). After day 21 both cytosol and nuclear oestrogen receptor concentrations fell and remained low until nuclear concentrations rose at day 40. Two consecutive daily injections of FSH/LH (5 i.u.) increased cell number over control in animals killed on day 22, gave no significant alteration in animals killed on day 26 or 28 but decreased numbers in animals aged 32 and 35 days. Only on day 22 was the increase in cell number associated with an increase in nuclear oestrogen receptor concentrations. Indeed on days 32 and 35 increased nuclear receptor concentrations were associated with a decreased cell number. PMID- 3102667 TI - Similarities in sequences and cellular expression between rat CD2 and CD4 antigens. AB - The MRC OX-34 antigen of rat T lymphocytes was purified and peptide sequences were obtained. Oligonucleotide probes were synthesized and cDNA clones coding for the antigen were isolated and sequenced to yield a predicted protein sequence for the molecule that fitted the peptide data. Comparison of this sequence with that for human CD2 determined by Sewell et al. showed that OX-34 is rat CD2. The primary structure of the molecule was notable for a moderately large cytoplasmic domain of unusual sequence and also for its highly significant relationship to CD4 antigen in the membrane proximal extracellular region and the transmembrane sequence. A relationship to the Ig superfamily can be argued for the two extra cellular domains of CD2, even though neither fits the standard pattern for Ig related domains. Within the T lymphocyte lineage, rat CD2 seemed to be present on all stages with the exception of approximately 50% of the thymic CD4-,CD8- cells. In addition, the antigen was prominent on most macrophages in the spleen but not found on peritoneal or liver macrophages. CD4 antigen is also expressed on T lymphocytes and macrophages, and thus CD2 and CD4 appear similar in their cellular expression as well as structural characteristics. PMID- 3102668 TI - A 275 basepair fragment at the 5' end of the interleukin 2 gene enhances expression from a heterologous promoter in response to signals from the T cell antigen receptor. AB - Using a transient transfection assay, we have defined the sequences required for the activation of the IL-2 gene in response to signals from the T cell antigen receptor. To do so we have transfected the human T cell line Jurkat with hybrid DNA constructs in which fragments from the IL-2 gene are linked to an indicator gene. The indicator gene product, as well as IL-2 production from the endogenous IL-2 gene were assayed after activation of the transfected Jurkat cells by various stimuli. We have demonstrated that a 275 bp fragment stretching from 52 to 326 bp upstream of the IL-2 gene transcription initiation site is required for expression of the linked indicator gene. This IL-2 gene fragment has several of the characteristics of a transcriptional enhancer element, in that it functions in both orientations and will enhance the expression from the promoter of an unrelated gene. Such enhancement occurred only after activation of Jurkat cells through the T cell antigen receptor. More specifically, this 275 bp fragment activated the expression of a linked gene after binding of a monoclonal antibody to the Jurkat T cell antigen receptor in the presence of PMA. In addition, calcium ionophore, which circumvents antigen receptor binding in T cell activation, induced the expression of the linked gene through this 275 bp sequence, in the presence of PMA. Finally, in a mutant Jurkat cell line lacking T3/antigen receptor complexes at the cell surface, no expression due to the IL-2 5' flanking region was seen after exposure to antibody to the T cell antigen receptor plus PMA or to PHA plus PMA. In contrast, calcium ionophore plus PMA did induce the expression of a linked gene through the IL-2 5' flanking region in the mutant Jurkat cell line. The responsiveness of the transfected hybrid genes containing the IL-2 regulatory region paralleled the expression of the endogenous IL-2 gene, as determined by IL-2 bioassays. We conclude that the 275 bp IL-2 sequence (-326 to -52 bp) is a target for the signal pathway originating at the T cell antigen receptor. Definition of this 275 bp target sequence should now permit the isolation of the molecules that bind to and activate the IL-2 gene. PMID- 3102669 TI - Alloreactive cytolytic T cell clones with dual recognition of HLA-B27 and HLA-DR2 antigens. Selective involvement of CD8 in their class I--directed cytotoxicity. AB - HLA-B27- responder cells were stimulated in vitro with HLA-B27.1+ lymphoblastoid cell lines, and alloreactive CTL clones were obtained by limiting dilution. Three of these clones specifically lysed B27.1+ targets. In addition, they also lysed homozygous DR2 targets with various degrees of efficiency, depending on the Dw specificity of the target cell. All three clones possessed a homogeneous CD3+,CD8+,CD4- phenotype and were also homogeneous upon subcloning. Cold-target inhibition analyses showed mutual inhibition of B27.1 target lysis by DR2 targets and vice versa. Lysis of B27.1 targets was selectively inhibited by anti-class I mAbs. In contrast, lysis of DR2 targets was inhibited only by anti-class II and anti-DR monomorphic antibodies, but not by anti-class I, anti-DQw1, or anti-DP antibodies. The results indicate that these clones display dual recognition for HLA-B27.1 and for HLA-DR2 and suggest that HLA-B27.1 may share at least one epitope that is closely related to some stimulatory Dw determinants present on the HLA-DR2 antigens. Lysis of both B27+ and DR+ targets was inhibited by an anti CD3 mAb. In contrast, an anti-CD8 antibody selectively inhibited the B27- but not the DR2-directed killing by these clones. The data support a stabilizing role of CD8 through its binding to the same class I (but not class II) molecule on the target cell bound by the T cell antigen receptor. PMID- 3102670 TI - Phenotype and proliferation of early B lymphocyte precursor cells in mouse bone marrow. AB - Bone marrow cells were examined by double immunofluorescent labeling techniques to detect determinants for the B lineage monoclonal antibody, 14.8, the nuclear enzyme, terminal deoxynucleotidyl transferase (TdT), cytoplasmic mu chains (c mu), and surface mu (s mu). In 8-9-wk-old C3H/HeJ mice, 14.8+ cells totalled 22.2% of all marrow cells (35 X 10(5) cells/femur). While many 14.8+ cells were c mu+ s mu- pre-B cells and s mu+ B lymphocytes (17.0%), the remainder (5.2%) were large cells lacking mu chains. After injecting vincristine sulfate, these 14.8+ mu- cells accumulated in mitosis at a rate of 13.5%/h (turnover time, 7.4 h). Their calculated total production rate (41 X 10(6) cells/whole marrow/d) exceeded that previously determined for large pre-B cells, suggesting some cell loss from the B lineage. TdT+ cells made up 1.8% of marrow cells and were mainly medium sized cells. They all lacked mu chains, but half (0.9%) bound 14.8 antibody at low to medium intensity. Three discrete cell populations were thus defined, differing in mean cell diameter TdT+ 14.8- mu-, 9.5 micron; TdT+ 14.8+ mu-, 10 microns; and TdT- 14.8+ mu-, 11.5 micron, presumptively representing a sequence of cell stages preceding the expression of mu chains in large pre-B cells (TdT- 14.8+ c mu+ s mu-, 11.5 microns). This work provides a tentative model of early progenitor cells and their proliferation in normal marrow as a basis for studies of perturbations and the control of B lymphocytopoiesis. PMID- 3102671 TI - The DNA sequence of the structural gene of gonococcal protein III and the flanking region containing a repetitive sequence. Homology of protein III with enterobacterial OmpA proteins. AB - The insert of a lambda gt11 clone expressing gonococcal protein III was sequenced. The deduced amino acid sequence showed a coding frame of 236 amino acids with a typical 22-amino-acid signal peptide, followed by the known NH2 terminal sequence of PIII. The mature protein has a molecular weight of 23,298. It was found that PIII had extensive and very striking homology to the carboxy terminal portion of enterobacterial OmpA proteins. The homology encompasses the OmpA domain that is believed to be located in the periplasmic space. If the disposition of PIII across the OM is analogous, then the surface-exposed domain consists of less than 40 amino acids. These include a potential 15-amino-acid disulfide loop, a feature not found in OmpA proteins. Hybridization studies with the sequenced insert indicated that it contained a repetitive sequence that occurred at least 20 times in the genome. By additional hybridization studies the area containing the repetitive sequence was narrowed to a region of 43 bp. This region contained an exact copy of the consensus sequence of a 26-bp repetitive sequence recently described. An analogous sequence recurs in an inverted orientation 53 bp downstream. PMID- 3102672 TI - Secretion of pyruvate. An antioxidant defense of mammalian cells. AB - Cells in culture are exposed to marked oxidative stress, H2O2 being one of the predominant agents. Pyruvate and other alpha-ketoacids reacted rapidly, stoichiometrically, and nonenzymatically with H2O2, and they protected cells from its cytolytic effects. All five human and murine cell types studied, both malignant and nonmalignant, released pyruvate at an initial rate of 35-60 microM/h/2.5 X 10(6) cells when placed in 1 ml pyruvate-free medium. After 6-12 h a plateau of 60-150 microM pyruvate was attained, corresponding to concentrations reported for normal human serum and plasma. The rate of pyruvate accumulation was almost doubled in the presence of exogenous catalase, suggesting that released pyruvate functions as an antioxidant. The rate of pyruvate accumulation was dependent on cell number. Succinate, fumarate, citrate, oxaloacetate, alpha ketoglutarate, and malate were not secreted in significant amounts from P815 cells; export was specific for pyruvate and lactate among the metabolites tested. Extracellular pyruvate was in equilibrium with intracellular stores. Thus, cells conditioned the extracellular medium with pyruvate at the expense of intracellular pyruvate, until homeostatic levels were attained in both compartments. We propose that cells plated at low density in the absence of exogenous pyruvate fail to thrive for two reasons: prolonged depletion of intracellular pyruvate and prolonged vulnerability to oxidant stress. PMID- 3102673 TI - Molecular dissection of the murine antibody response to streptococcal group A carbohydrate. AB - Monoclonal antibodies (mAb) to streptococcal group A carbohydrate (GAC) are encoded by a minimum of two VH, four JH, four V kappa, three J kappa, one V lambda, and one J lambda gene segments. The IdX, IdI-1, and Id5 idiotypic determinants are expressed by anti-GAC mAb and are found on free kappa chains. Each pattern of these determinants is encoded by a distinct V kappa gene segment, apparently without the requirement for a particular J kappa, VH, or JH gene segment, or somatic mutation. In contrast, the binding site-associated idiotypic determinant IdI-3a does not correlate with any single V or J gene segment. PMID- 3102674 TI - Phenotypic changes of bone marrow-derived mast cells after intraperitoneal transfer into W/Wv mice that are genetically deficient in mast cells. AB - The ability of mouse IL-3-dependent, bone marrow culture-derived mast cells (BMMC) to generate serosal mast cells (SMC) in vivo after adoptive transfer to mast cell-deficient mice has been defined by chemical and immunochemical criteria. BMMC differentiated and grown from WBB6F1-+/+ mouse progenitor cells in medium containing PWM/splenocyte-conditioned medium synthesized a approximately 350,000 Mr protease-resistant proteoglycan bearing approximately 55,000 Mr glycosaminoglycans, as defined by gel filtration of each. Approximately 85% of the glycosaminoglycans bound to the cell-associated BMMC proteoglycans were chondroitin sulfates based upon their susceptibility to chondroitinase ABC digestion; HPLC of the chondroitinase ABC-generated unsaturated disaccharides revealed these glycosaminoglycans to be chondroitin sulfate E. As determined by heparinase and nitrous acid degradations, approximately 10% of the glycosaminoglycans bound to BMMC proteoglycans were heparin. In contrast, mast cells recovered from the peritoneal cavity of congenitally mast cell-deficient WBB6F1-W/Wv mice 15 wk after intraperitoneal injection of BMMC synthesized approximately 650,000 Mr protease-resistant proteoglycans that contained approximately 80% heparin glycosaminoglycans of approximately 105,000 Mr. Thus, after adoptive transfer, the SMC of the previously mast cell-deficient mice were like those recovered from the normal WBB6F1-+/+ mice that were shown to synthesize approximately 600,000 Mr proteoglycans that contained approximately 80% heparin glycosaminoglycans of approximately 115,000 Mr. As assessed by indirect immunofluorescence staining and flow cytometry using the B1.1 rat mAb (an antibody that recognizes an epitope located on the neutral glycosphingolipid globopentaosylceramide), approximately 5% of BMMC bound the antibody detectably, whereas approximately 72% of the SMC that were harvested from mast cell-deficient mice 15 wk after adoptive transfer of BMMC were B1.1-positive; approximately 82% of SMC from WBB6F1-+/+ mice bound the antibody. These biochemical and immunochemical data are consistent with the results of previous adoptive transfer studies that characterized mast cells primarily on the basis of morphologic and histochemical criteria. Thus, IL-3-dependent BMMC developed in vitro, cells that resemble mucosal mast cells, can give rise in vivo to SMC that express phenotypic characteristics of connective tissue mast cells. PMID- 3102675 TI - Rosetting of activated human T lymphocytes with autologous erythrocytes. Definition of the receptor and ligand molecules as CD2 and lymphocyte function associated antigen 3 (LFA-3). AB - CD2, also known as LFA-2, T11, and the E rosette receptor, is a T lymphocyte surface protein functionally important in adhesion to target cells and T cell triggering. LFA-3 is a widely distributed cell surface protein that functions in adhesion on target cells. We find that LFA-3 is expressed on human E, and that CD2 is a receptor for LFA-3 that mediates T cell adhesion to human E. Pretreatment of T lymphocytes with CD2 mAb or of E with LFA-3 mAb inhibits rosetting. Purified CD2 molecules bind to human E and inhibit rosetting. 125I-CD2 binding to E is inhibited by LFA-3 mAb; reciprocally, binding of LFA-3 mAb to human E is inhibited by pretreatment with purified CD2. Higher concentrations of CD2 aggregate human E; aggregation is inhibited by mAb to LFA-3. PMID- 3102676 TI - Purified lymphocyte function-associated antigen 3 binds to CD2 and mediates T lymphocyte adhesion. AB - CD2 is a T lymphocyte glycoprotein that functions in adhesion of T lymphocytes and also as a putative receptor for activation signals. Functional data suggest that LFA-3, a widely distributed cell surface glycoprotein, may be the biological ligand of CD2. We have purified LFA-3 from human erythrocytes and characterized the purified protein functionally. LFA-3 bound specifically to CD2+ cells, and this binding was inhibited by CD2 mAb. Conversely, purified LFA-3 inhibited binding of CD2 mAb to cells, and the concentration required for this effect suggests that LFA-3 half-saturated CD2 at 1-5 nM LFA-3. Purified LFA-3 inhibited rosetting of human and sheep erythrocytes with CD2+ T lymphoma cells and T lymphocytes, and mediated aggregation of a CD2+ T lymphoma cell line. Purified LFA-3 reconstituted into planar membranes mediated efficient CD2-dependent adhesion of T lymphoblasts. These data demonstrate that LFA-3 is a ligand for CD2 and that LFA-3 can mediate T lymphocyte adhesion. PMID- 3102677 TI - Activation of mouse peritoneal macrophages by monoclonal antibodies to Mac-1 (complement receptor type 3). AB - Several features of activation of mouse peritoneal macrophages were elicited by 1 2-d exposure to submicrogram concentrations of anti-Mac-1 (M1/70), a rat monoclonal antibody that reacts with the alpha chain of complement receptor type 3 (Mac-1). The changes induced included enhanced capacity to secrete H2O2 when triggered with PMA, decreased secretion of proteins, increased expression of Ia antigen and decreased phagocytosis of particles. These changes closely resembled those induced by rIFN-gamma in type, extent, and time course. The concentration of M1/70 IgG resulting in 50% of the maximal activation of macrophage H2O2 releasing capacity averaged 0.18 +/- 0.03 micrograms/ml. This activation was not blocked by anti-FcR mAb, and could be reproduced with M18/2, a mAb against beta chain of Mac-1, suggesting that a direct ligation of Mac-1 with mAb was responsible for the activation. Neither depletion of T cells nor addition of neutralizing Abs to IFN-gamma or TNF-alpha prevented M1/70-mediated macrophage activation. Moreover, F(ab')2 of M1/70, or plating of macrophages on C3bi-coated surfaces, inhibited the activation of macrophages by rIFN-gamma. These findings suggest that Mac-1 (CR3) may play an important role in macrophage activation. PMID- 3102678 TI - Phenotypic heterogeneity of melanoma. Relation to the differentiation program of melanoma cells. AB - Phenotypic heterogeneity is a characteristic feature of tumor lesions in patients with melanoma. Variability can be observed in cell morphology, pigmentation, and antigen expression. To test whether phenotypic heterogeneity could be the result of events regulated during cell differentiation, we evaluated the expression of a panel of differentiation traits on melanoma cells. Metastatic melanoma lesions from two patients, designated FD and AP, were examined histologically and found to contain mixed populations of cells. Established melanoma cell lines derived from each of these lesions were subcloned at early passage in culture (passages 7 and 8) to create a panel of clones derived from each tumor. There was heterogeneity in the expression of differentiation-related traits in clones, corresponding to distinct phenotypes observed within the original tumors. Clones from patient FD corresponded to early to intermediate stages of melanocyte differentiation, and clones from patient AP ranged from intermediate to late stages. The influence of cholera toxin and PMA on differentiation of parental cultures and subclone was studied. Results of induction studies demonstrated a number of features of differentiation of melanoma cells: regulation of differentiation traits is coordinated as a program of traits expressed sequentially at specific stages; early traits, such as the epidermal growth factor receptor and the melanoma chondroitin sulfate proteoglycan antigen, are downregulated as melanoma cells differentiate, whereas late markers, including melanin, tyrosinase activity, and antigens expressed in mature melanosomes, are upregulated; Ia (class II major histocompatibility) antigens are characteristically expressed on melanomas corresponding to early or intermediate stages of differentiation and are regulated as part of the differentiation program; minimal changes in stage of differentiation were observed during induction of parental cultures with either cholera toxin or PMA, whereas definite shifts in differentiation could be induced in selected cloned subpopulations. We conclude that melanoma cells are not frozen at a specific stage of differentiation, but rather are capable of differentiating when exposed to appropriate signals. Diversity in the differentiation state of melanoma cells can account for much of the phenotypic heterogeneity observed in melanoma lesions. PMID- 3102680 TI - DRGs for physicians: a next step to socialized medicine. PMID- 3102679 TI - Rearrangements of immunoglobulin and T cell receptor beta and gamma genes are associated with terminal deoxynucleotidyl transferase expression in acute myeloid leukemia. AB - The cell origin of the rare terminal deoxynucleotidyl transferase (TdT)-positive acute myeloid leukemias (AML) was investigated at the molecular level, by examining the configuration of the Ig H (Igh) and L (Ig kappa, Ig lambda) chain gene regions, and of the T cell receptor (TCR) beta and T cell rearranging (TRG) gamma loci. In 8 of the 10 TdT+ AML analyzed (classified as myeloid according to morphological and cytochemical criteria, and to the reactivity with one or more antimyeloid mAbs), a rearrangement of the Igh chain gene was found. In TdT- AML, evidence of an Igh gene reorganization was instead observed only in 2 of the 42 patients studied. Furthermore, evidence of TCR-beta and/or TRG-gamma gene rearrangement was observed in four AML, all of which belonged to the Igh rearranged TdT+ group. In three cases (one TdT+ and two TdT-), the Ig kappa L chain gene was also in a rearranged position. These findings demonstrate a highly significant correlation between TdT expression and DNA rearrangements at the Igh and TCR chain gene regions and support the view that this enzyme plays an important role in the V-(D)-J recombination machinery. Overall, the genomic configuration, i.e., JH gene rearrangement sometimes coupled to a kappa L chain and TCR gene reorganization, similar to that found in non-T-ALL, suggests that in most cases of TdT+ AML, the neoplastic clone, despite the expression of myeloid related features, is characterized by cells molecularly committed along the B cell lineage. PMID- 3102681 TI - Congenital dilatation of the biliary tract in infancy and childhood. PMID- 3102682 TI - Effect of post-operative infusion of amino acid and total parenteral nutrition on muscle high-energy phosphates. PMID- 3102683 TI - Sensitive immunoradiometric assay for thyrotropin to distinguish primary hyperthyroidism and secondary hypothyroidism from normals. PMID- 3102684 TI - Genetic control of scrapie: incubation period and plaque formation in I mice. AB - The host component of control of scrapie incubation period in the mouse is manifested largely through the action of the Sinc gene. Only one mouse strain (VM) has been found that is p7p7 (prolonged incubation for ME7 agent) and two other strains have been derived from VM. All other strains, designated s7s7, have a short incubation for ME7. In the present study, the I strain was shown to fulfil the criteria that are characteristic of mouse strains with the p7 allele of Sinc: a comparatively long incubation period for ME7 and a short incubation period for 22A, the incubation period for F1 hybrid mice (s7s7 X p7p7) either fell between the incubation periods for the parental strains (with ME7) or were longer than either parent (with 139A and 22A), amyloid plaques occurred following injection of ME7 and 87V but not after 22A or 139A, lesion profiles for four scrapie strains were similar in I mice and p7p7 mouse strains, and injection of 87V led to disease in less than 300 days. Finally, allelism tests using F1 hybrid mice (I X a p7p7 mouse strain) and progeny of backcrosses between these F1 mice and I mice failed to reveal the segregation of additional major genes affecting scrapie incubation period. PMID- 3102685 TI - Electron microscopic study of the process of DNA ejection from the head of PL-1, a Lactobacillus casei phage. AB - The process of DNA ejection from the head of PL-1, a Lactobacillus casei ATCC 27092 phage, was studied by electron microscopy by counting the number of ghost particles with empty heads among phages already adsorbed to the cell. The process of DNA ejection was temperature- and live cell-dependent. PMID- 3102686 TI - Recombinant human interferon-gamma inhibits adenovirus multiplication in vitro. AB - The susceptibility of adenovirus to the inhibitory effect of human interferons in vitro was investigated. We tested recombinant human interferons-alpha 2, -beta 1 and -gamma against adenovirus serotypes 1 and 5 (group C), 3 and 7a (group B), and a wild strain isolated from an acutely ill child who later died. Pretreatment of WISH cells with interferon-gamma for 24 h induced a dose-dependent inhibition of multiplication of all adenovirus strains tested, the TCID50 varying from 25 to 90 IU/ml. Human interferon-alpha 2 was unable to decrease adenovirus multiplication, while interferon-beta 1 at 2000 IU/ml slightly lowered the yield of adenovirus. Similar results were obtained in HEp-2 and FS-4 cells, while A-549 and peripheral blood mononuclear cells were insensitive to interferon-gamma. The difference between the effects of interferon-gamma and interferon-alpha and -beta on adenovirus multiplication in vitro suggests that its mechanism of antiviral action is different. PMID- 3102687 TI - Neurofibromatosis of the head and neck. PMID- 3102688 TI - Carbon dioxide inhalation treatments of neurotic anxiety. An overview. AB - A lucky chance more than 30 years ago revealed the remarkable efficacy of single inhalations of high concentrations of carbon dioxide in eliminating or markedly reducing free-floating anxiety. The reduction of anxiety lasts for days, weeks, or longer--well beyond the persistence of carbon dioxide in the body. The effects are explicable on the hypothesis that free-floating anxiety is anxiety conditioned to continuously present sources of stimulation, such as background noise or the awareness of space or time, and that the anxiety response habit is weakened when the anxiety is inhibited by the competition of responses that carbon dioxide induces. More recently, it has become apparent that inhalations of carbon dioxide, applied in a different manner, are effective in overcoming maladaptive anxiety responses to specific stimuli, e.g., social stimuli. The substance is also proving to be a valuable resource in the treatment of the common variety of panic attacks. PMID- 3102689 TI - Structural variations in soluble iron complexes of models for ferritin: an x-ray absorption and Mossbauer spectroscopy comparison of horse spleen ferritin to Blutal (iron-chondroitin sulfate) and Imferon (iron-dextran). AB - Variations in the turnover of storage iron have been attributed to differences in apoferritin and in the cytoplasm but rarely to differences in the structure of the iron core (except size). To explore the idea that the iron environment in soluble iron complexes could vary, we compared horse spleen ferritin to pharmaceutically important model complexes of hydrous ferric oxide formed from FeCl3 and dextran (Imferon) or chondroitin sulfate (Blutal), using x-ray absorption (EXAFS) and Mossbauer spectroscopy. The results show that the iron in the chondroitin sulfate complex was more ordered than in either horse spleen ferritin or the dextran complex (EXAFS), with two magnetic environments (Mossbauer), one (80%-85%) like Fe2O3 X nH2O (ferritinlike) and one (15%-20%) like Fe2O3 (hematite); since sulfate promotes the formation of inorganic hematite, the sulfate in the chondroitin sulfate most likely nucleated Fe2O3 and hydroxyl/carboxyls, which are ligands common to chondroitin sulfate, ferritin and dextran most likely nucleated Fe2O3 X nH2O. Differences in the structure of the iron complexed with chondroitin sulfate or dextran coincide with altered rates of iron release in vivo and in vitro and provide the first example relating function to local iron structure. Differences might also occur among ferritins in vivo, depending on the apoferritin (variations in anion-binding sites) or the cytoplasm (anion concentration). PMID- 3102690 TI - Cerebral metabolism of 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine in the primate. AB - The tracers 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (6-[18F]fluoro-L-DOPA) and L-[14C]DOPA were injected simultaneously into rhesus monkeys, and the time course of their metabolites was measured in the striatum and in the occipital and frontal cortices. In the striatum, 6-[18F]fluoro-L-DOPA was metabolized to 6 [18F]fluorodopamine, 3,4-dihydroxy-6-[18F]fluorophenylacetic acid, and 6 [18F]fluorohomovanillic acid. The metabolite pattern was qualitatively similar to that of L-[14C]DOPA. 6-[18F]Fluorodopamine was synthesized faster than [14C]dopamine. In the frontal cortex, the major metabolite was also 6 [18F]fluorodopamine or [14C]dopamine. In the occipital cortex, the major metabolite was 3-O-methyl-6-[18F]fluoro-L-DOPA. On the basis of these data, the images obtained with 6-[18F]fluoro-L-DOPA and positron emission tomography in humans can now be interpreted in neurochemical terms. PMID- 3102691 TI - Effect of digestion with phospholipase A2 on endogenous protein phosphorylation in particulate fractions from rat brain synaptosomes. AB - The endogenous phosphorylation of synapsin 1 in cyclic AMP-containing media was greatly decreased by digestion of synaptic vesicles and synaptosomal membranes with phospholipase A2, suggesting that the system is functionally dependent on the membrane structure. Treatment of the synaptic vesicle fraction with phospholipase A2 also caused a small but significant inhibition of the Ca2+/calmodulin-dependent phosphorylation of the same protein. The Ca2+/calmodulin-dependent phosphorylation of other major acceptors, and the basal phosphorylation of a 52-kD acceptor enriched in the vesicle fraction, remained unchanged after cleavage of the membrane phospholipids with phospholipase A2. The significance of the selective effect of phospholipase A2 treatment on endogenous membrane phosphorylation is discussed. PMID- 3102692 TI - Arachidonoyl-coenzyme A synthetase and nonspecific acyl-coenzyme A synthetase activities in purified rat brain microvessels. AB - Purified rat brain microvessels were prepared to demonstrate the occurrence of acyl-CoA (EC 6.2.1.3) synthesis activity in the microvasculature of rat brain. Both arachidonoyl-CoA and palmitoyl-CoA synthesis activities showed an absolute requirement for ATP and CoA. This activity was strongly enhanced by magnesium chloride and inhibited by EDTA. The apparent Km values for acyl-CoA synthesis by purified rat brain microvessels were 4.0 microM and 5.8 microM for palmitic acid and arachidonic acid, respectively. The apparent Vmax values were 1.0 and 1.5 nmol X min-1 X mg protein-1 for palmitic acid and arachidonic acid, respectively. Cross-competition experiments showed inhibition of radiolabelled arachidonoyl-CoA formation by 15 microM unlabelled arachidonic acid, with a Ki of 7.1 microM, as well as by unlabelled docosahexaenoic acid, with a Ki of 8.0 microM. Unlabelled palmitic acid and arachidic acid had no inhibitory effect on arachidonoyl-CoA synthesis. In comparison, radiolabelled palmitoyl-CoA formation was inhibited competitively by 15 microM unlabelled palmitic acid, with a Ki of 5.0 microM and to a much lesser extent by arachidonic acid (Ki, 23 microM). The Vmax of palmitoyl-CoA formation obtained on incubation in the presence of the latter fatty acids was not changed. Unlabelled arachidic acid and docosahexaenoic acid had no inhibitory effect on palmitoyl-CoA synthesis. Both arachidonoyl-CoA and palmitoyl-CoA synthesis activities were thermolabile. Arachidonoyl-CoA formation was inhibited by 75% after 7 min at 40 degrees C whereas a 3-min heating treatment was sufficient to produce the same relative inhibition of palmitoyl-CoA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102693 TI - Purification and properties of calmodulin-lysine N-methyltransferase from rat brain cytosol. AB - A S-adenosylmethionine:protein-lysine N-methyltransferase (EC 2.1.1.43) has been purified from rat brain cytosol 7,080-fold with a yield of 8%, using octopus calmodulin as a substrate. It contains a lysine residue that is not fully methylated. The enzyme was purified by ammonium sulfate fractionation, Sephacryl S-200 gel filtration, and phosphocellulose and octopus calmodulin-Sepharose affinity chromatographies. Among protein substrates, it was highly specific toward octupus calmodulin. The Km values for octopus calmodulin and S-adenosyl-L methionine were found to be 2.2 X 10(-8) M and 0.8 X 10(-6) M, respectively. The molecular weight was estimated to be 57,000 by gel filtration and the pH optimum was between 7.5 and 8.5. The enzyme was stimulated in the presence of 10(-7) M Mn2+ and 10(-4) M Ca2+. HPLC of the acid hydrolysate of methyl-3H-labeled calmodulin showed the formation of epsilon-N-mono, epsilon-N-di, and epsilon-N trimethyllysine. Reverse-phase HPLC of tryptic peptides of the methyl-3H-labeled calmodulin demonstrated that the labeled N-methyllysine lies in the 107-126 peptide. These findings suggest that this enzyme methylated a specific lysine residue of octopus calmodulin. PMID- 3102694 TI - Effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine and its metabolite 1 methyl-4-phenylpyridine on acetylcholine synthesis in synaptosomes from rat forebrain. AB - 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and its metabolite, 1-methyl 4-phenylpyridine (MPP+), have been shown to cause a number of lesions in dopaminergic pathways of the nigro-striatal region of the brain. However, data on the effects of these neurotoxins on other aspects of brain metabolism are scarce. The data presented here show that MPTP and MPP+ inhibit glucose oxidation via the tricarboxylic acid cycle, and acetylcholine synthesis in synaptosomal preparations from rat forebrain. Monoamine oxidase B inhibitors (e.g., pargyline, MDL 72145) relieve the inhibition caused by MPTP but not MPP+. The inhibitory effects of MPP+ on glucose oxidation and acetylcholine synthesis are a consequence of the decreased glucose metabolism in synaptosomes and are consistent with its role as an inhibitor of the Complex I (NADH-CoQ reductase) of the mitochondrial respiratory chain. PMID- 3102695 TI - Amphetamine and reserpine deplete brain biogenic amines and alter blow fly feeding behavior. AB - HPLC with electrochemical detection was used to determine the levels of p hydroxyphenylethanolamine (octopamine), 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (5-HT) in the brains of control, reserpine, and d amphetamine-treated blow flies, Phormia regina Meigen. Parallel studies were carried out to assess the effects of the two drugs on fly feeding behavior, measured as mean acceptance threshold: the minimum sucrose concentration to which the average fly in a population will respond by proboscis extension when its tarsi contact the solution. In saline-injected control flies, all three amines were found at levels of approximately 2 pmol/brain. Thirty minutes after injection with d-amphetamine (12 micrograms/fly), brain octopamine was depleted by 85%, whereas dopamine and 5-HT were depleted by 70%. Reserpine (5 micrograms/fly) caused 70% depletion of dopamine and greater than 90% depletion of both octopamine and 5-HT 24 h after injection. However, the effect of reserpine was much slower in onset (hours versus minutes) and more persistent (days versus hours) than was the effect of d-amphetamine. With either drug, the time course of amine depletion closely matched the time course of the increase in feeding threshold observed in drug-treated flies. These results suggest that CNS pools of the biogenic amines, octopamine, dopamine, and 5-HT are important in governing blow fly responsiveness to food stimuli. PMID- 3102696 TI - Amaurosis fugax under the age of 40 years. AB - Sixteen patients who presented under the age of 40 years with amaurosis fugax have been studied. Follow up from the time of presentation was one to 13 years with a median of 3 years. One patient whose attacks of uniocular visual loss were associated with headache developed a permanent uniocular field defect. None of the other patients has suffered permanent visual loss, or had symptoms of cerebral or myocardial ischaemia. All angiograms were normal and it is suggested that carotid angiography is unnecessary in this age group. Four out of ten patients studied demonstrated evidence of platelet hyperaggregability to low concentrations of arachidonic acid and adenosine diphosphate with spontaneous aggregation. However, in six patients treated with aspirin, including three with previous platelet hyperaggregability, there was no change in the frequency of their attacks implying that the observed platelet abnormalities were not the cause of the amaurosis fugax. PMID- 3102697 TI - Regional cerebral blood flow in man at rest and during exercise. AB - Regional cerebral blood flow (rCBF) of the left hemisphere was measured in 12 healthy young men at rest and during physical work on a bicycle ergometer in the supine position at work-load levels of 25 W or 100 W using the intravenous 133Xe method. Regional mean cerebral blood flow, regional gray-matter flow, and relative gray-matter weight was determined for six regions of interest. Arterial blood pressure, pulse frequency and expiratory CO2 concentration were recorded. Cerebral blood flow in all regions was significantly (P less than 0.001) higher during exercise than at rest. The increase in the 100 W group (24.7%) was significantly (P less than 0.05) greater than in the 25 W group (13.5%), but resting blood flow levels and alveolar CO2 concentrations were also different in both groups. Mean arterial blood pressure, pulse frequency and alveolar CO2 concentrations, but not arterial pCO2, were significantly higher during exercise and there was a faster washout of whole-body xenon. The CBF increase was interpreted as a combined effect of elevated systemic blood pressure and functionally activated brain metabolism. There was no evidence of impaired cerebral autoregulation. PMID- 3102698 TI - Effect on intracranial pressure of furosemide combined with varying doses and administration rates of mannitol. AB - The first part of this study investigated the combined use of furosemide and mannitol in the treatment of elevated intracranial pressure (ICP). Two groups of dogs were studied to determine if renal excretion of mannitol was altered in the presence of furosemide. No significant difference in excretion was noted between the two groups. Fifteen animals were used in other studies to identify the most advantageous sequence of administration of furosemide and mannitol. Infusion of mannitol followed by furosemide 15 minutes later resulted in the most profound and sustained ICP reduction. The effect on ICP reduction of varying the mannitol dose was observed in studies using single doses of 0.5 gm/kg, 0.75 gm/kg, and 1 gm/kg. The larger mannitol dose, resulting in a greater blood-brain osmotic gradient, proved to be the most efficacious in ICP reduction. A further 15 animals were used in investigations to determine whether changing the rate of delivery of the most effective mannitol dose (1 gm/kg) influenced resultant ICP reduction. The results indicated that rapid administration (2 ml/kg/min) produced higher peak serum concentrations of mannitol and more profound lowering of ICP than the same dose delivered at slower rates. PMID- 3102699 TI - Indium-111 T101 monoclonal antibody is superior to iodine-131 T101 in imaging of cutaneous T-cell lymphoma. AB - We have reported that [111In]T101 is highly effective in the detection of cutaneous T-cell lymphoma (CTCL) in nodal and cutaneous (erythroderma and tumor) sites. This study compares the biodistribution of [131I]T101 (1 to 7.1 mg, 2 mCi) in four patients with CTCL; two of these patients also received [111In]T101 (1 mg, 5 mCi). There was rapid clearance of [131I]T101 from whole-body, spleen, liver, and bone marrow, with evidence of loss of 131I tracer from the T101. Lymph node uptake was minimal in three of four patients, and there was no localization in skin lesions. This contrasted with [111In]T101 where there was prolonged retention of activity in these organs and excellent uptake in skin tumors, erythroderma, and lymph nodes. The study showed that [131I]T101 was suboptimal for imaging CTCL patients and demonstrates that the isotope or labeling method can dramatically alter the apparent biodistribution and tumor targeting of a given monoclonal antibody. PMID- 3102700 TI - Thymic localization of gallium-67 in pediatric patients with lymphoid and nonlymphoid tumors. AB - To determine the significance of 67Ga localization in the thymus of children, 142 67Ga photoscans from 45 children with various tumors were studied. Sixty-nine photoscans were taken for 17 cases of lymphoma, 73 photoscans were made for 28 cases of nonlymphoid tumors. Thymic localization of 67Ga was positive in 16 (36%) of the 45 patients and in 30 (21%) of the 142 photoscans. Positive thymus scans were seen in five (29%) of the 17 cases of lymphoma and 11 (39%) of the 28 solid tumors. The positive incidence was highest (90%) in ages 1-2 yr old. Of the eight grade 2 (strong positive) patients, the thymus in one case of Hodgkin's disease was diagnosed as malignant and the other seven solid tumor cases were nonmalignant. Most of the latter seven cases became positive after beginning of treatment (surgery and/or chemotherapy). Although the precise mechanism is not well understood, thymic localization of 67Ga may represent immunologic response to tumors, especially in infants with nonlymphoid neoplasms. PMID- 3102701 TI - Radionuclide diagnosis and therapy of neural crest tumors using iodine-131 metaiodobenzylguanidine. AB - The successful application of [131I]metaiodobenzylguanidine (MIBG) in diagnosis and therapy of pheochromocytoma has led to its use in other tumors which derive from the neural crest and potentially concentrate this radiopharmaceutical as well. In the present series, [131]MIBG total-body scintigraphy was used for detection of neuroblastoma in 47 patients and 47 cases of other neural crest tumors. The method was found to be as reliable in neuroblastoma (sensitivity 95%, specificity 100%), as it is in pheochromocytoma. Although other neural crest tumors may concentrate [131I]MIBG, this is not a consistent finding; however, it is useful to investigate which tumors do, as this may provide an alternative treatment modality for some patients. Although followup is still very short, preliminary results of therapeutic use of [131I] MIBG in 21 patients indicate that this treatment modality may be effective in neuroblastoma and malignant pheochromocytoma. PMID- 3102702 TI - Iodine-131 MIBG scintigraphy of the extremities in metastatic pheochromocytoma and neuroblastoma. AB - Iodine-131 MIBG scintigraphy may be used to determine the presence or absence of metastases to the appendicular skeleton in malignant pheochromocytoma and neuroblastoma. Normal bones show no uptake of [131I]MIBG and the joints are seen as photon-deficient areas surrounded by background muscle activity. Discrete concentrations of radioactivity in bone are often seen in patients with malignant pheochromocytoma and neuroblastoma. Bone marrow involvement in neuroblastoma may be indicated by diffuse uptake of [131I]MIBG or focal accumulation at the metaphyses. Uncommonly, bone involvement may not be displayed by the [131I]MIBG images. Since conventional bone scanning agents may also fail to detect these tumors, skeletal scintigraphy with both [131I]MIBG and [99mTc]MDP is necessary to reliably stage malignant pheochromocytoma and neuroblastoma. PMID- 3102703 TI - Utility of total body gallium-67 scintigraphy in a patient with AIDS related complex. PMID- 3102704 TI - Comparing two methods of hospital orientation for cost effectiveness. PMID- 3102705 TI - Multiple shift patient classification: is it necessary? AB - Efficient, cost-effective patient classification systems are an essential component of information needed for staffing projections, budgeting, productivity monitoring, and determining the cost of nursing services. Data collection on every shift is typical of GRASP-based patient classification systems. In this study, comparisons among multiple shift measurements showed that no relevant information was being gained by multiple daily assessments of patient care requirements. PMID- 3102706 TI - Glycine availability limits maximum hippurate synthesis in growing rats. AB - The rate-limiting step for hippurate synthesis from sodium benzoate (NaB) was investigated in growing rats. Rats fed a glycine-and serine-free L-amino acid diet were injected daily with saline or varying doses of NaB. Growth was monitored for 4 d, after which time rats were killed and livers were assayed for glycine, serine, benzoyl-CoA, benzoyl-CoA ligase and glycine benzoyl-CoA transferase. In control animals, liver glycine and serine concentrations were 2.18 and 1.63 mumol/g wet wt, respectively; benzoyl-CoA was not detectable. In rats injected with 600 mg NaB/kg body wt per day, liver glycine and serine concentrations decreased to 68 and 78% of control values, respectively, and benzoyl-CoA accumulated (0.52 mumol/g wet wt). As the dose of NaB was increased, liver benzoyl-CoA concentration increased, and growth of the rats was markedly impaired. The activities of benzoyl-CoA ligase and glycine benzoyl-CoA transferase were unchanged after NaB treatment. In a second experiment, rats were treated with growth-impairing doses of NaB. When the diet was supplemented with serine and glycine, growth was normalized, liver glycine and serine concentrations returned to control levels, and benzoyl-CoA accumulation was markedly diminished. These results suggest that glycine availability limits maximum hippurate synthesis in vivo. PMID- 3102707 TI - Teratogenic potential of valproic acid. PMID- 3102708 TI - Indium-111 leukocyte scintigraphic detection of subclinical osteomyelitis complicating delayed and nonunion long bone fractures: a prospective study. AB - Twenty patients were studied prospectively with indium-labeled leukocyte imaging to evaluate its effectiveness in differentiating noninfected delayed or nonunion from osteomyelitis complicating these entities. All patients underwent an open surgical procedure within 24 h of the scan. Bone specimens from the nonunion site were obtained for microbiological and histological analysis to confirm the presence or absence of osteomyelitis. In these twenty patients, the sensitivity of the indium scintigraphy was 100%, the specificity 100%, and the overall accuracy 100%. Indium-labeled leukocyte scintigraphy is significantly more accurate than 99mtechnetium and 67gallium imaging had been, when studied earlier, in detecting subclinical osteomyelitis complicating nonunion. Indium-labeled leukocyte scintigraphy should supplant sequential technetium and gallium studies in this patient population when the surgeon must determine whether subclinical osteomyelitis is complicating fracture management of delayed and nonunions. PMID- 3102709 TI - [Intergenus cell fusion between L-forms of Streptococcus faecalis and Staphylococcus aureus. I. Attempts to induce L-forms of oral streptococci particularly S. faecalis]. PMID- 3102710 TI - [Intergenus cell fusion between L-form of Streptococcus faecalis and staphylococcus aureus. II. Cell fusion between stable or unstable L-form cells of Streptococcus faecalis and those of Staphylococcus aureus]. PMID- 3102711 TI - Intravenous gammaglobulin therapy for prophylaxis of infection in high-risk neonates. AB - The safety and effectiveness of intravenously administered gammaglobulin therapy for prophylaxis of infection was evaluated in 133 high-risk neonates. The infants were stratified into two groups: infants with birth weight less than or equal to 1500 g and gestational age less than or equal to 34 weeks, and infants with birth weight greater than 1500 g and receiving intensive care and assisted ventilation. Forty-three infants in group 1 and 25 in group 2 were given gammaglobulin at a dose of 0.5 g/kg/wk, for 1 month in group 1 and during intensive care in group 2. Forty infants in group 1 and 25 in group 2 served as controls. Serum total IgG and group B streptococcus-, Escherichia coli-, and CMV-specific IgG levels similar to those in adult controls were observed in the treated infants 2 hours after gammaglobulin administration. In the treated infants in group 1, the incidence of infection was 51%, and of septicemia 5%; in the controls the incidence of infection was 77% (P less than 0.02), and of septicemia 20% (P less than 0.05). Infection was the main cause of death in one treated and six control infants in group 1 (P less than 0.04). In the infants with birth weight greater than 1500 g receiving intensive care and assisted ventilation, no significant differences were observed in the incidence of infection or septicemia in treated and control infants. No side effects were observed after intravenous gammaglobulin administration. These data show that intravenously administered gammaglobulin is both safe and effective for prophylaxis of infection in preterm very low birth weight infants. PMID- 3102712 TI - Comparison of a pediatric versus standard amino acid formulation in preterm neonates requiring parenteral nutrition. PMID- 3102713 TI - In vitro excystation of Sarcocystis capracanis, Sarcocystis cruzi and Sarcocystis tenella (Apicomplexa). AB - Improved rates of in vitro excystation of sporozoites from sporocysts of Sarcocystis capracanis, Sarcocystis cruzi, and Sarcocystis tenella were obtained by pretreating sporocysts with an aqueous sodium hypochlorite (NaOCl) solution followed by incubation in excysting fluid (EF). After pretreatment with NaOCl, sporocysts were washed 4 times in Hanks' balanced salt solution and then incubated in various EF (pH 7.4) at 38.5 C in 5% CO2-95% air. Maximum rates of excystation (free sporozoites/(sporozoites in sporocysts + free sporozoites) X 100) for all 3 species of Sarcocystis occurred at 4 hr after incubation in EF. These rates were 17% for S. capracanis after incubation in EF containing 2% trypsin + 10% caprine bile; 90% for S. cruzi in 2% trypsin + 10% bovine bile; and 20% for S. tenella in 2% trypsin + 10% caprine bile. Only a 40% excystation rate occurred in sporocysts of S. cruzi that had been stored previously for 14 days in aqueous potassium dichromate. Excysted sporozoites of S. capracanis, S. cruzi, and S. tenella penetrated and developed to mature meronts in bovine pulmonary artery endothelial cells or bovine monocytes. PMID- 3102714 TI - The pediatric trauma score as a predictor of injury severity in the injured child. AB - The ability of the Pediatric Trauma Score (PTS) to accurately predict the degree of injury severity of the injured child was assessed by comparing two separate groups of pediatric trauma victims. The first group consisted of 110 patients evaluated at a regional pediatric trauma center whose data was collected and assessed by a single investigator. The second group consisted of a similar matched cohort of 120 patients from the National Pediatric Trauma Registry whose data was collated from multiple participating institutions. In both cases, a linear relationship between PTS and Injury Severity Score (ISS) was documented that was statistically significant to P less than .001. The linear regression coefficients of each group were similar as was the distribution of PTS and ISS. This study documents the validity of the PTS as an initial assessment tool and confirms its reliability as a predictor of injury severity. PMID- 3102715 TI - Total intestinal aganglionosis: a new technique for prolonged survival. AB - Total small bowel aganglionosis is uniformly fatal; and prolonged nutritional treatment for the resulting severe short bowel syndrome in the absence of a therapy designed to achieve a functional bowel length has not been warranted. We report an operative technique, long segment small bowel myectomymyotomy, which has produced a functioning length of intestine capable of supporting ever increasing amounts of enteral nutrition. A term female was noted to have neonatal intestinal obstruction, and two laparotomies proved total colonic and near-total small bowel aganglionosis. At 2 months of age reoperation was done and the aganglionosis was proved to extend to 7 cm below the ligament of Treitz. From this transition zone to 10 cm distally, a myectomy was done removing a 1 cm wide length of seromuscular tissue to the level of the submucosa. From the distal end of the myectomy, another 40 cm of bowel received an antimesenteric border myotomy cutting to the submucosal level followed by spreading of the cut surface to a width of 1 cm. This left the patient with 55 to 60 cm of small bowel from the ligament of Treitz to the end of the myotomy at which point an end ostomy was created. The remainder of the small bowel was excised and the colon exteriorized as a mucous fistula. The patient was continued on total parenteral nutrition alone for ten days at which time small volume enteral feeds were introduced. By 5 months of age, 25% of calories were enteral; by 6 months, 33% of calories were enteral; and by 8 months, 45% of intake was enteral.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102716 TI - Must fat emulsions and parenteral nutrition solutions be given through separate circuits? AB - To test the stability of fat emulsions with parenteral nutrition (PN) solutions, 10% soybean fat emulsion (FE) was suspended in PN solutions containing amino acids, electrolytes, vitamins, and different glucose concentrations. Six different mixtures were prepared and analyzed after 15 minutes or 24 hours, under transmission electron microscope: 10% fat emulsion (FE); FE + PN solution with 5% glucose (15 minutes); FE + PN solution with 5% glucose (24 hours); FE + PN with 12.5% glucose (24 hours); FE + PN with 25% glucose (24 hours); and FE + pure glucose 50% (24 hours). The addition of FE to PN solutions containing 5% to 25% glucose did not cause coalescence, aggregation, or confluence of the liposomes or damage to their surface in the first 24 hours after admixture. However, the suspension of fat emulsion in a 50% glucose solution coalesced liposomes and the droplets were nearly all aggregated. We conclude that mixtures of FE with PN solutions with glucose are stable for at least 24 hours and are suitable for clinical use. PMID- 3102717 TI - Studies on pharmacological activation of human serum IgG by chemical modification and active subfragments. V. Mechanism of anti-inflammatory action of carboxamide methylated L-chain (Fr. I-L) and H-chain (Fr. I-H) from human serum IgG. AB - Using the xylene ear method in mice, it was demonstrated that the reduced and carboxamide-methylated fragments of human serum IgG (Fr. I-H and Fr. I-L) significantly suppressed capillary permeability. It was also shown that leucocyte emigration and protein leakage into and esterase activity of the pouch fluid, which was accumulated by carboxy-methyl cellulose injections, were suppressed by the administration of the fragments. Moreover, the lipid peroxide level was lowered by both Fr. I-H and Fr. I-L in the liver of either carrageenin-induced, paw edema-bearing or kaolin pouch inflammation in rats. The facts obtained in this study indicated the mechanisms of the anti-inflammatory effects of Fr. I-H and Fr. I-L were mainly caused by both the inhibitory effect on leucocyte emigration into the site of injury and stabilization of the membrane by inhibiting lipid peroxidation of the inflammatory tissue. PMID- 3102718 TI - A pharmacodynamic model for the activity of antibiotics against microorganisms under nonsaturable conditions. AB - An exact mathematical solution was derived to a pharmacodynamic model which illustrates bacterial survival in the presence of antibiotics. In this report the survival of Pseudomonas aeruginosa in the medium of an initial concentration of 0.64 mM (320 mg/L) of piperacillin [(2S,5R,6R)-6-[(R)-2-(4-ethyl-2,3-dioxo-1- piperazinecarboxyamido)-2-phenylacetamido]-3,3-dimethyl-7- oxo-4-thia-1 azabicyclo[3.2.0]heptane-2-carboxylate] was well described by the derived model for up to 24 h. The bacterial killing by the antibiotic and apparent natural growth rate constants were 2955.3 h-1 X mol-1 and 0.5698 h-1, respectively. The functional equation was also fit to the data of ampicillin against Escherichia coli under simulated in vivo conditions. The optimal multiple dosing time and the minimum critical concentration to achieve antimicrobial action can be readily calculated from the developed model. Computer simulations were made to examine the effect on microbial survival of such factors as initial antibiotic concentration (Co), elimination half-life (t1/2), kill rate constant (K) of the antibiotic, and apparent growth rate constant (Kapp) of the test organism. PMID- 3102719 TI - Intranasal administration of peptides: nasal deposition, biological response, and absorption of desmopressin. AB - The nasal administration of desmopressin [1-(3-mercaptopropionic acid)-8-D arginine-vasopressin] in humans was investigated. Desmopressin solutions containing 99mTc-labeled human serum albumin were administered intranasally as a spray, using two metered-dose pumps, or as drops, using a rhinyle catheter or a single-dose pipet. Images of the sites of deposition and rates of clearance were monitored quantitatively by gamma scintigraphy. Plasma levels of desmopressin were measured using a highly sensitive and specific radioimmunoassay. The biological response was determined by measuring circulating levels of F VIII, the antihemophilia factor. The sprays were deposited mainly anteriorly, from which small portions were cleared slowly into the nasal pharynx. In contrast, the drops were deposited mostly posteriorly and cleared very rapidly in large portions; some were swallowed immediately. Plasma levels showed that desmopressin was absorbed to a greater extent after administration of the spray with a 2 to 3-fold increase in the relative bioavailability compared with the drops. The biological response was clearly enhanced after spray administration and produced similar increases in F VIII activity. A linear correlation was observed between maximum plasma desmopressin levels and maximum F VIII activity. The use of an intranasal spray device can deposit well-controlled doses within the nasal cavity, which remain there sufficiently long to provide a clear enhancement in absorption and bioavailability. PMID- 3102720 TI - Dermal penetration enhancement profile of hexamethylenelauramide and its homologues: in vitro versus in vivo behavior of enhancers in the penetration of hydrocortisone. AB - Several amides of cyclic amines were prepared and tested as penetration enhancers in the diffusion of various drugs through hairless mouse skin in vitro. Hexamethylenelauramide (hexahydro-1-lauroyl-1H-azepine) was selected as a broad spectrum penetration enhancer worthy of further study. Later, the duration of the effect of various enhancers on the penetration barrier in vivo was determined by evaluating the in vitro diffusion of hydrocortisone through skins that had been pretreated in vivo. We found that the longer the pretreatment, the smaller the amount of penetrated hydrocortisone. Furthermore, our results suggested that differences exist in the retention of various enhancers in living mouse skin. The in vitro pretreatment experiments revealed that the penetration through dead skin is slow compared with the penetration through living skin. Neither the nature of the receptor phase, nor the increased temperature of the in vitro experiments, explain the striking differences between the in vivo and the in vitro experiments. Finally, the penetration of hydrocortisone through the stratum corneum in the presence of enhancers, as well as the penetration of 1 dodecylhexahydro-2H-azepin-2-one (laurocapram), hexamethylenelauramide, and oleic acid, were determined using a stratum corneum stripping technique. More hydrocortisone penetrated through the stratum corneum during the first 3 h in the presence of hexamethylenelauramide than in the presence of laurocapram or oleic acid. PMID- 3102721 TI - [Antineoplastic effects of carnosine and beta-alanine--physiological considerations of its antineoplastic effects]. AB - Antineoplastic effects of carnosine (CAR) and beta-alanine (ALA), were examined in vivo using ddY mice implanted with the solid tumor Sarcoma-180. The sarcoma was treated with trypsin, 10(5) cells were implanted subcutaneously in the back of the animals, and CAR and ALA were administered subcutaneously 2 cm from the implantation site starting on the next day. The animals treated with ALA alone showed prolongation of survival to a T/C value of 132%; the growth of the tumor was inhibited and mortality reduced in those treated with CAR alone. Regression of the tumor was observed in the animals treated with either drug. The effects of these agents were enhanced when administered in combination with the non-specific active immuno-enhancing agent OK-432. More than half the animals treated with CAR and OK-432 survived the observation period (T/C greater than 218%), and survival was prolonged in those treated with ALA and OK-432 to a T/C value of 132%. The agents also showed potent antineoplastic effects on Sarcoma-180 when the tumor had been attenuated in vivo with mitomycin C (MMC). PMID- 3102722 TI - Nasogastric feeding tubes. PMID- 3102723 TI - Metabolism of glucose by human embryos. AB - Glucose turnover, as measured by CO2 production, lactate accumulation and carbon incorporation from [U-14C]glucose as sole energy substrate, was low on the 2nd day of culture of human embryos resulting from in-vitro fertilization but above that of unfertilized oocytes. In general, all parameters of metabolism increased substantially during the following 2 days of development but the rate of increase in lactate production was greater than that of CO2, especially between Days 3 and 4. Within developing embryos, no correlation was evident between the metabolic turnover of glucose and the method of patient stimulation, the morphological quality of embryos or the apparent rate of cleavage in culture. The results indicate that, before Day 3 of development, glucose is not effective as an energy source for the human embryo because of a blockade to glycolysis similar to that in mouse embryos. PMID- 3102724 TI - Identification of bovine trophoblast protein-1, a secretory protein immunologically related to ovine trophoblast protein-1. AB - This paper demonstrates that a group of proteins, representing a major secretory component of cattle conceptuses, is immunologically related to ovine trophoblast protein-1 (oTP-1), a principal product of culture Day 13 to 21 sheep conceptuses. Conceptuses from cows (Day 17-18) and ewes (Day 16-17) were cultured for 24 h in the presence of L-[3H]leucine. By using a rabbit antiserum to oTP-1 and Ouchterlony double-immunodiffusion analysis it was shown that material in the bovine conceptus culture medium was serologically related, but not identical, to oTP-1. A solid-phase radiobinding assay indicated that the cross-reacting bovine secretory component had an affinity for anti-oTP-1 antibody similar to that of oTP-1. Anti-oTP-1 antiserum specifically immunoprecipitated a group of 6-8 polypeptides from culture medium of cow conceptuses which, when analysed by two dimensional gel electrophoresis, fell into two major molecular weight classes (22,000 and 24,000) with isoelectric points between 6.5 and 6.7. These immunoprecipitated polypeptides, defined as bTP-1, constituted the major secretory products of Day 16-25 cow conceptuses. They were larger and more basic than oTP-1 polypeptides (Mr about 18,000; pI 5.4-5.7). Anti-oTP-1 antiserum also recognized the major translation product of Day 17 bovine conceptus mRNA, a polypeptide significantly smaller (Mr approximately 18,000) than the secreted protein. It is suggested that oTP-1 and the homologous bovine protein may play similar roles in the phenomenon of maternal recognition of pregnancy in the two species. PMID- 3102725 TI - The paradox of gold compounds: activators or inhibitors? PMID- 3102726 TI - Rioprostil prevents gastric bleeding induced by nonsteroidal antiinflammatory drugs in dogs and arthritic rats. AB - Gastrointestinal irritation is the most significant side effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAID) for treatment of arthritic conditions. Rioprostil, a primary alcohol prostaglandin E1 analog, prevents gastric bleeding induced by several NSAID in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of rioprostil (50 micrograms/kg BID for 15 days) did not influence the course of the adjuvant disease in rats or alter the antiinflammatory or analgesic effect of the NSAID. In a 13 week efficacy study in dogs, rioprostil (40-60 micrograms/kg, PO) completely prevented gastric hemorrhagic lesions induced by daily administration of aspirin. PMID- 3102727 TI - Studies on the effect of D-penicillamine, gold thioglucose and methotrexate on streptococcal cell wall arthritis. AB - Intraperitoneal administration of group A streptococcal cell walls to rats induces an acute arthritis that resolves and is followed by a chronic lesion. The effect of low dose methotrexate, D-penicillamine and gold thioglucose has been investigated in this model. Whereas D-penicillamine and gold thioglucose had no effect on the hind paw inflammation and joint destruction (radiological assessment) associated with the lesion, methotrexate treatment suppressed both of these variables. Spleen cells derived from cell wall treated arthritic rats were hyporesponsive to concanavalin A (Con-A) and were deficient in the synthesis of interleukin 2 (IL-2). Spleen cells derived from methotrexate treated rats exhibited an improved response to Con-A and their ability to synthesize IL-2 was significantly enhanced. PMID- 3102728 TI - HLA typing, platelet associated immunoglobulins and anticardiolipin antibody. PMID- 3102729 TI - Chorea, systemic lupus erythematosus, circulating lupus anticoagulant. PMID- 3102730 TI - The Bhopal disaster. PMID- 3102731 TI - Training public health engineers in developing countries. PMID- 3102732 TI - Growth and development of Saudi infant and pre-school children. PMID- 3102734 TI - Stigmatized illnesses in Africa. PMID- 3102733 TI - The keys of paradise: Godfrey's Cordial and children in Victorian Britain. PMID- 3102735 TI - Screening and treatment of urinary schistosomiasis in Dar es Salaam. PMID- 3102736 TI - Smoking habits among male students at King Saud University. PMID- 3102737 TI - The microbiology of Legionnaires' disease. PMID- 3102738 TI - Epidemiology of spontaneous abortions--the effect of previous abortions. PMID- 3102739 TI - Food proscriptions in traditional medicine. PMID- 3102740 TI - Legionnaires' disease outbreaks--the engineering implications. PMID- 3102741 TI - Occupational health and safety in a newly industrializing country. PMID- 3102742 TI - Preparation and evaluation of electrophilic derivatives of phenylbutazone as inhibitors of prostaglandin-H synthase. AB - The chemical syntheses and biological evaluation of several potential irreversible inhibitors for prostaglandin (PGH) synthase are described. These inhibitors were modeled after the nonsteroidal antiinflammatory (NSAI) drug phenylbutazone (4-n-butyl-1,2-diphenyl-3,5-pyrazolidinedione). Electrophilic functionalities such as an alpha-bromoacetamide, an alpha-chloroacetamide, a phenylurethane, a propargyl chloride, and several alpha,beta-unsaturated Michael acceptors were incorporated at the 4-position of the pyrazolidinedione ring structure. None of the derivatives showed evidence of irreversible inhibition of PGH synthase, although several were nearly as potent inhibitors of this enzyme as phenylbutazone. The nitrile obtained from 1,4-conjugate addition of cyanide to one of the unsaturated derivatives was considerably more potent as an inhibitor of PGH synthase than was phenylbutazone. PMID- 3102743 TI - Synthesis of D-oxa tricyclic partial ergolines as dopamine agonists. AB - A series of hetero fused hexahydro-1,4-benzoxazines has been synthesized and evaluated for dopamine agonist activity. This class of compounds is another example in which an oxygen substitution in the D ring of a partial ergoline or ergoline retains dopaminergic properties. Compound 10, trans-(+/-)-4,4a,5,6,8a,9 hexahydro-5-propyl-2H,7H-pyrazolo[4,3-g] [1,4]benzoxazine, is a D-ring analogue of trans-(+/-)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-2H-pyrazolo[3,4-g]qu ino line (1, LY141865) and also a des-A-ring analogue of 9-oxaergoline. Compounds 10, 2 aminohexahydrothiazolo[1,4]benzoxazine 11, and 2 aminohexahydropyrimido[1,4]benzoxazine 12 possess dopaminergic activity in prolactin inhibition and 6-hydroxydopamine lesioned rat turning assays. PMID- 3102744 TI - Referral rates of senior family practice residents in an ambulatory care clinic. AB - Discretion regarding the need for and appropriateness of consultations and referrals is an important dimension of clinical competence. However, the process of consultation by medical residents has not been well studied. In the study reported here, a review was made of office-based referrals requested by second- and third-year family practice residents over a three-year period. Significantly lower referral rates were found for the second-year residents than the third-year residents. Possible explanations for this finding included: differences in approach to case management, lack of referral experience by second-year residents, and differences in case mix. Although no explicit protocol existed for the distribution of patients to the residents, differences in case mix and patient age between the patients seen by the two groups of residents accounted for the difference in referral rates. This difference implies that patient distribution in graduate training programs may not be random as commonly thought. PMID- 3102745 TI - Biotyping, serotyping and phage typing of Streptococcus faecalis isolated from dental plaque in the human mouth. AB - Thirty Streptococcus faecalis isolates from mixed dental plaque samples were classified into four groups on the basis of biotype, tetracycline susceptibility, phage type and serotype combinations. The organisms were from patients on haemodialysis, from staff of the dialysis unit, and from controls. Three biotypes were distinguished by seven biochemical tests: production of acid from inositol, sucrose and xylose; rapid or delayed production of acid from sorbitol; gelatin liquefaction; and production of alkaline phosphatase and beta-galactosidase. With a set of eight typing antisera for S. faecalis, 15 strains were non-typable, 12 were serotype 1 and three were serotype 19. With a set of 17 bacteriophages specific for S. faecalis, all of the oral isolates were typable; 40% were lysotype I1 and the remainder lysotype V6b. On the basis of biotype-serotype phage-type combinations, indications of possible spread of strains between haemodialysis patients and dialysis unit staff were obtained. Biotyping and serotyping of 13 German isolates of S. faecalis of phage type I1 from four clinical sources and tripartite typing of three control strains provided additional evidence for the potential of biotyping in distinguishing between strains of identical serotype and phage type. One oral isolate of S. faecium was of phage type XX. None of the oral isolates of S. faecalis, of which 14 exhibited delayed sorbitol fermentation, reacted with group-G streptococcal grouping reagents or antiserum. Slow sorbitol fermentation does not appear to be a definitive phenotypic marker for S. faecalis strains possessing antigens that react with both group-D and group-G grouping reagents. PMID- 3102746 TI - Theories of the etiology of multiple sclerosis: a critical review. AB - In summary, research studies to date have not identified a unitary cause of MS; rather, genetic predisposition (particularly, inherited immunoregulatory abnormalities) and environmental links in the causal chain of disease (antigenic exposures, trauma, or other insults) have been postulated to interact with each other and with additional host susceptibility factors (acquired faulty immune system regulation, age, nutritional status, endocrine status, etc.). Two mechanisms have been proposed as their final common pathway: dysmyelination (i.e., defective myelin production) and inadequate myelin maintenance. Myelin production, turnover rate, and neurological function are all apparently normal prior to disease onset, although studies addressing possible preexisting lipoprotein metabolic defects have not been performed in MS patients as in laboratory animals. The demyelination process characteristic of the disease appears to result from inadequate maintenance due to an active degradative process, rather than from deficient formation or a simple passive metabolic imbalance between anabolic and catabolic processes, as had been suggested by Sperry and Waelsch (205). Among other lines of evidence, it is offered that deficient replacement postpubertally would not explain the rapid onset of symptoms often seen in MS. Accelerated myelin destruction could be due either to faulty regulation of the rate-limiting enzymes, for which there is no substantiation, or to immune system malfunction, for which the evidence is mounting. Immune system attack seems to be both humoral and cell-mediated, but the triggers remain unknown. This article has briefly but critically reviewed toxins, trauma, thrombosis, subacute fat embolism, viruses, and biochemical factors in the etiology of MS, with emphasis on hormonal and other types of mediation of the immune response. PMID- 3102747 TI - malM, a new gene of the maltose regulon in Escherichia coli K12. II. Mutations affecting the signal peptide of the MalM protein. AB - malM is the last gene of the malK-lamB-malM operon of Escherichia coli K12. It encodes a periplasmic protein. Mutations affecting the hydrophobic core of the N terminal extension of the MalM protein have been isolated. They result in an increase in amount and specific activity of a MalM-LacZ hybrid protein. This result confirms that the signal peptide of the MalM protein is functional. PMID- 3102748 TI - Asymmetrical core structure in phycobilisomes of the cyanobacterium Synechocystis 6701. AB - The light-harvesting complex of cyanobacteria and red algae, the phycobilisome, has two structural domains, the core and the rods. Both contain biliproteins and linker peptides. The core contains the site of attachment to the thylakoid membrane and the energy transfer link between the phycobilisome and chlorophyll. There are also six rod-binding sites in the membrane-distal periphery of the core. The structure of phycobilisomes in the cyanobacterium Synechococcus 6301 was studied by Glazer, who proposed a model for the internal organization of the bicylindrical core. In the construction of that model, it was necessary to make arbitrary decisions between two possible locations for one of the trimeric protein complexes within a core cylinder and between two possible orientations of the basal core cylinders relative to one another. We isolated the tricylindrical cores from an ultraviolet-light-induced mutant of the cyanobacterium Synechocystis 6701 and obtained, by partial dissociation, a unique core substructure that maintained some contacts between the two basal cylinders. From its structure and spectral properties, we conclude that this particle is a central core substructure that resulted from dissociation of the two layers of peripheral trimers in the intact core. The compositions of this particle and the dissociated trimers were inconsistent with the proposed location of one of the trimers in the 6301 core model, but supported the placement of that trimer in the alternative position within the basal core cylinder. Rod-binding sites within the central core substructure were studied by partial dissociation of the short-rod phycobilisomes from another mutant of 6701. This dissociation generated particles that were interpreted as being central core substructures with the two basal rods attached. The appearance of these particles in the electron microscope suggested that both basal rods would be localized towards the same side of the intact core. Such an asymmetrical arrangement of basal rods is supported by previously published edge-views of intact cores with basal rods from strain 6701. These observations suggest a parallel arrangement of the basal cylinders with respect to each other, creating an asymmetrical core. A phycobilisome model was constructed that incorporated core asymmetry. This model predicts the energy transfer pathways from the basal and upper rods to specific trimers in the core. PMID- 3102749 TI - Ecdysterone and heat shock induction of transfecting and endogenous heat shock genes in cultured Drosophila cells. AB - Various combinations of the heat shock genes of Drosophila melanogaster are transcribed in response to elevated temperature and also during normal development and in certain ecdysterone-treated Drosophila cell lines. Here I describe an homologous transient expression system using Schneider 3 cells, a Drosophila line responsive to ecdysterone. I compare the constitutive, ecdysterone and heat shock-induced accumulation of transcripts of five transfecting heat shock genes (hsp82, hsp70, hsp28, hsp26 and hsp23) to the accumulation of transcripts of their endogenous counterparts. The pattern of expression of the transfecting genes under these various conditions is generally similar to that of the endogenous genes. PMID- 3102750 TI - In vitro fertilization and development of ova obtained from female mice treated with aminopterin and mitomycin C. AB - We examined the effects of mitomycin C and aminopterin on ovulation in vivo and, fertilization, subsequent cleavage and implantation in slc-ICR female mice using methods of fertilization and culture in vitro. Chemicals were injected into mice at the MI (meiosis I) stage or 3 hours before the MI stage in order to examine their toxicity. Mitomycin C did not affect ovulation, but decreased the rate of fertilization. A high dose of mitomycin C (4 mg/kg) inhibited fertilization and the development of ova to the 2-cell stage. Aminopterin affected neither ovulation nor fertilization. At either the MII (meiosis II) stage or 3 hours before the MII stage, high doses (4 and 2 mg/kg) of mitomycin C arrested cleavage and implantation. The cleavage was blocked frequently between the 3-4 cell stage and the 5-8 cell stage. Aminopterin affected neither cleavage nor implantation. PMID- 3102751 TI - Short-term toxicity study of 4-dimethylaminoazobenzene in marmosets. AB - The marmoset, a small non-human primate, has rarely been used in toxicological studies. A short-term toxicity study was performed on common marmosets (BW = 330 +/- 32 g). Fifteen male marmosets received oral administration of DAB at a dose level of 56 mg/kg/day and 4 control animals received corn oil alone for a period of 15 days. Hematological, biochemical, histopathological and bone marrow examinations were carried out on the 5th, 10th and 15th day of treatment. Body weight decreased continuously and two animals died on day 10. Decreases in RBC, Hb and Ht and increases in MCV and WBC were observed. Uric acid and glucose were increased and AlP and LAP were decreased. Aldolase, GOT and GPT were increased by day 10, and thereafter recovery of aldolase to the control level and decreases of GOT and GPT were observed. Relative organ weights of the liver, kidney, spleen and adrenal were increased. Histologically, C-cell hyperplasia of the thyroid and slight changes of the liver were noted. Marrow total cell counts were not changed, but the G/E ratio was reduced. Thus, macrocytic anemia, an increase of marrow erythroblasts due to anemia and changes of biochemical parameters indicating liver injury were observed in marmosets; these findings were similar to those in rats in the previous experiments. PMID- 3102752 TI - The effect of burn wound size on resting energy expenditure. AB - Numerous formulas have been used to estimate the calorie requirements of hypermetabolic burned patients. With the recent development of instrumentation for indirect calorimetric measurements, questions have been raised concerning the validity and accuracy of the early equations. Because metabolic rate decreases during the course of wound healing, we attempted to determine the magnitude of hypermetabolism and the accuracy of the Curreri formula in patients with various wound sizes. Twenty-eight patients with a mean initial burn size of 29% body surface area (BSA) had measurements of resting energy expenditure (REE) at regular intervals during their postburn course. Concomitantly, basal energy expenditure (BEE) was calculated from the Harris-Benedict equation; and the predicted energy needs were calculated using the Curreri formula adjusted for current wound size (ACEE). Three significantly different burn size (%BSA) groups were identified: Group 1, 1-10%; Group 2, 11-30%; and Group 3, 31-60% BSA. The measured REE was 27, 35, and 50% greater than the BEE in Groups 1, 2, and 3, respectively (p less than 0.001). The ACEE underestimated REE by 7% in Group 1, and overestimated REE by 13 and 35% in Groups 2 and 3, respectively (p less than 0.001). Resting energy expenditure should be measured at regular intervals in individuals with open burn wounds greater than 10% BSA in order to adjust nutritional support appropriately. PMID- 3102753 TI - Impaired expression of interleukin-2 receptor (IL2R) in the immunosuppressed burned patient: reversal by exogenous IL2. AB - The capability of exogenous recombinant Interleukin 2 (rIL2) to increase expression of the IL2 receptor (IL2R), and to augment the in vitro proliferative response of lymphocytes from immunosuppressed burned patients (5-80% full thickness burns) was examined. Throughout the postburn period the percentage of IL2R-bearing cells in Concanavalin A-activated cultures of patients' peripheral blood mononuclear cells (PBMC) was measured by direct immunofluorescence with monoclonal anti-IL2R antibodies. Mitogen-induced IL2R expression was decreased by 40-90% in cultures of patients' PBMC, parallel to their reduced alloreactivity. During this period of immunosuppression supplementation of the mitogen-activated cultures with recombinant IL2 (20 U/ml) significantly increased the number of IL2R-expressing cells in all patients studied. However, IL2-induced enhancement of blastogenesis in the MLR was observed only with the patients who, in mitogen activated cultures, sustained numbers of IL2R-endowed cells at least 50% of their baseline (the level within the first 24 hours postburn). Also, unstimulated PBMC of the same responding patients demonstrated a restoration of proliferation in the presence of rIL2. These patients were survivors. Thus the proliferative response correlated well with the number of Con A- but not rIL2-induced IL2R expressing cells. These results suggest that in burned patients, IL2 up-regulates its receptors, but they may represent low-affinity nonfunctional receptors. Thus thermal injury appears to affect expression of functional (high-affinity) receptors. PMID- 3102754 TI - Failure of TPN supplementation to improve liver function, immunity, and mortality in thermally injured patients. AB - Hypermetabolism with negative nitrogen balance and immune deficiencies characterize the systemic response to major thermal injury. Patients with burns greater than 50% of the total body surface area (TBSA) initially have poor gastrointestinal function, making it difficult to deliver sufficient enteral calories to meet nutritional requirements. Controversy has developed over whether to supplement oral alimentation with total parenteral nutrition (TPN) early in their treatment. This study randomly assigned 28 patients with burns greater than 50% TBSA to receive TPN supplementation or no TPN supplementation in the first 10 days postburn. Patients receiving TPN supplementation had significantly lower T cell helper-to-suppressor cell ratios than the unsupplemented group. However, there was no difference in mortality between the groups (eight in each). All patients who died developed hepatomegaly associated with fatty infiltration cholestasis and antemortem liver function abnormalities, indicating that this syndrome is the result of burn injury itself, not TPN. PMID- 3102755 TI - The effects of Schistosoma haematobium infestation on the vermiform appendix: the Nigerian experience. AB - In a prospective study of 518 consecutive appendices removed at surgery for symptomatic appendicitis, 32 appendices showed evidence of chronic Schistosoma haematobium appendicitis (a frequency of 6.2%). As the diagnosis can only be confirmed by histology of the removed appendix, the authors believe that in endemic areas chronic S. haematobium appendicitis may not be as rare as the few recorded cases would seem to suggest. Appendiceal mucosal ulceration with chronic inflammatory infiltration and fibrosis of the appendiceal wall leading to chronic appendicitis may be due to intense deposition of ova in the appendix wall, particularly the submucosa, by the adult worm. PMID- 3102756 TI - The effect of nutritional status and support on morbidity and mortality of bladder cancer patients treated by radical cystectomy. AB - The role of nutritional assessment and support in patients with bladder carcinoma undergoing radical cystectomy is controversial. Morphometric, visceral protein and cell-mediated immune statuses were measured in 33 patients with bladder cancer treated by radical cystectomy. Malnourished patients had greater operative morbidity, operative mortality and days of intensive care than their nutritionally normal counterparts. Kaplan-Meier survival plots showed a tendency to early death of disease in the malnourished patients with convergence of survival rates after 36 months. Of the malnourished patients 7 had extensive nutritional support, and 6 had no parenteral and minimal enteral or oral support. Operative morbidity and mortality rates were higher in the nutritionally supported than in the unsupported groups. Nutritional support in the immediate perioperative period probably does little to alter operative complications. PMID- 3102757 TI - Significance of testicular size measurement in andrology: II. Correlation of testicular size with testicular function. AB - The testicular sizes of 305 men were measured by a recently developed orchidometer and related to 9 other known parameters of testicular function. Mean testicular size had the strongest correlation with serum follicle-stimulating hormone levels, total sperm count and sperm concentration, while a significant correlation also was noted with sperm motility, percentage of live sperm, sperm morphology (normal and immature forms), and serum luteinizing hormone and testosterone levels. Sperm quantity had stronger correlations with testicular size than did sperm quality, although both were impaired in testes smaller than 14 ml. It is concluded that the size of the testis bears a direct correlation with testicular function and, thus, it can be helpful to assess rapidly andrological status during the initial physical examination. PMID- 3102758 TI - Total bone uptake in management of metastatic carcinoma of the prostate. AB - The status of patients with skeletal metastases from prostatic carcinoma was determined from a quantitative uptake and retention measurement of the bone scanning radiopharmaceutical 99mtechnetium-methylene diphosphonate. Whole body counts were performed 5 minutes and 24 hours after intravenous administration of 99mtechnetium-methylene diphosphonate, and were expressed as the percentage uptake by the skeleton at 24 hours. Skeletal uptake determinations were done in 29 patients with prostatic cancer (17 with osseous metastases) who were evaluated at 3 to 6-month intervals. Group 1 consisted of patients who responded to therapy and achieved remission, group 2 included patients with relapse or progressive disease, group 3 consisted of those with metastases who were in remission for longer than 6 months and group 4 included those without evidence of any bony metastases. The baseline mean +/- standard deviation 24-hour skeletal uptake values were 46.1 +/- 12.0 per cent in group 1, 34.3 +/- 13.9 per cent in group 2, 27.0 +/- 5.9 per cent in group 3 and 28.9 +/- 5.5 per cent in group 4. At 3 to 6 months the values in group 1 (responders) decreased by 18 per cent, while those in group 2 (relapse or progression) increased by 19 per cent and those in group 3 (remission) increased by 1.5 per cent. The quantitative 24-hour skeletal uptake test was performed easily, reproducible and at least as useful as concurrent chemical blood tests and subjective bone scan interpretations. PMID- 3102759 TI - Kinetics of dissolution of calcium oxalate calculi with calcium-chelating irrigating solutions. AB - Dissolution of calcium oxalate urinary calculi was studied in vitro. Rate constants were calculated by measuring the concentration of calcium in solution during dissolution. Various irrigating agents, including ethylenediaminetetraacetic acid (EDTA) and other calcium-chelating substances, were tested at different concentrations and pH values. EDTA was the most effective agent in dissolving calcium oxalate calculi. When EDTA was used, the rate of dissolution depended on both concentration and pH. At a pH of 7.5 or 10.0, the rate of dissolution increased progressively with the EDTA concentration. At each concentration tested, dissolution was faster at a pH of 10.0 than at a pH of 7.5. Calculated rate constants were extrapolated to determine whether in vivo irrigation with EDTA solutions is clinically practical. Even at an EDTA concentration of 0.03 M at a pH of 7.5, a two mm. calculus could be dissolved within 48 hr. Although dissolution of calcium oxalate calculi is not a practical first-line treatment, it might be a useful adjunct to percutaneous stone removal or extracorporeal shock wave lithotripsy. PMID- 3102760 TI - Enhanced inhibition of anticancer drugs by human recombinant gamma-interferon for human renal cell carcinoma in vitro. AB - We studied the inhibitory effect of seven anticancer drugs and alpha-, recombinant beta-, and recombinant gamma-interferons on the in vitro growth of two established human renal cell carcinomas and 16 renal cell carcinomas obtained from patients using monolayer culture and the double-layer soft agar system. Recombinant gamma-interferon was the most effective of three types of interferon. Combined treatment with recombinant gamma-interferon and some anticancer drugs inhibited the cell growth in both cell lines more than treatment with each drug alone. Treatment with recombinant gamma-interferon and cisplatinum or 5 fluorouracil following a 24-hour incubation with the interferon was more effective than when interferon and the drug were given simultaneously. Treatment using doxorubicin, cisplatinum, or vinblastine with recombinant gamma-interferon synergistically inhibited colony formation in 11 of the 16 renal cell carcinomas that showed clonal growth. Our results suggest that treatment with anticancer drugs in combination with recombinant gamma-interferon is effective for renal cell carcinoma. PMID- 3102761 TI - Leukocyte depletion enhances cultured endothelial retention on vascular prostheses. AB - Approximately 90% of endothelial cells that are seeded or cultured onto vascular prostheses are lost from the flow surface within 24 hours of implantation. To determine the contribution of leukocytes to endothelial cell loss, 111In-labeled, cultured canine jugular venous endothelial cells were grown to confluence on fibronectin-coated polyester elastomer tubes measuring 4 mm inner diameter and 30 mm in length. Autogenous cell-lined tubes were implanted as bilateral carotid replacement grafts in six dogs made leukopenic by cyclophosphamide. Similar unilateral grafts were placed in 12 control dogs. Grafts were removed and perfusion-fixed from six control animals after 2 hours of in vivo arterial perfusion and from the other six animals after 6 hours of perfusion. One graft was removed and perfusion-fixed from each leukopenic animal after 2 hours of implantation and the other after 6 hours. Attachment of endothelial cells to the grafts was measured by indium-labeling technique. Retention of endothelium on grafts removed after 2 hours was measured by planimetric counting with scanning electron microscopy and on those removed after 6 hours by radioisotope quantification. Endothelial cell retention after 2 hours was 37.6% +/- 27.0% in control dogs and 97.0% +/- 3.4% in leukopenic animals (p less than 0.0007). After 6 hours retention was 35.9% +/- 23.2% in control animals and 86.5% +/- 6.0% in leukopenic animals (p less than 0.0009). Leukocyte surface activity was present in less than 1% of the leukopenic dogs compared with 8.5% of the other in vivo midgrafts after 2 hours. These results suggest that leukocytes play a significant role in the loss of seeded endothelium from vascular prostheses. PMID- 3102762 TI - Effect of compliance mismatch on vascular graft patency. AB - The hypothesis that a mismatch in compliance between a vascular graft and its host artery is detrimental to graft patency was tested by implanting paired arterial autografts, prepared with differential glutaraldehyde fixation of carotid arteries in the femoral arteries of dogs. These grafts differed only in circumferential compliance: they were 100% (compliant) vs. 40% (stiff) as compliant as the host artery. Their flow surfaces were equivalent, as determined by physicochemical measurements and scanning electron microscopy; both lacked viable cells, as determined by in vitro cell culture. In 14 dogs, eight stiff and two compliant grafts became occluded within 3 months, the latter doing so within 24 hours after their contralateral counterparts. Cumulative patencies were 85% and 37% for compliant and stiff grafts, respectively (p less than 0.05) and 100% and 43%, excluding the two dogs with bilateral graft failures (p less than 0.01). We conclude that even with near optimal flow surfaces, compliance mismatch is deleterious to graft patency. PMID- 3102763 TI - Infection of white-tailed deer (Odocoileus virginianus) in Michigan with Jamestown Canyon virus (California serogroup) and the importance of maternal antibody in viral maintenance. AB - Sera collected from a captive population of white-tailed deer (Odocoileus virginianus) penned in the lower peninsula of Michigan were assayed over a 29-mo period for neutralizing antibody to California serogroup viruses. In all, 130 individual white-tailed deer were bled one to 22 times between June 1983 and November 1985. Of the 130 sampled after active transmission had ceased, or passage of maternal antibody in colostrum had occurred, only one (0.8%), a newborn fawn, had no serum neutralizing antibody to California group viruses. All 18 1-yr-old does sampled acquired specific neutralizing antibody to Jamestown Canyon (JC) virus within a 6-wk period in 1984 and within a 10-wk period in 1985 indicating the prevalence of infection in this nonimmune age group was 100% for 2 successive yr. All 32 2- to 7-yr-old adult does and eight bucks sampled between June 1983 and June 1985 had specific neutralizing antibody to JC virus. No white tailed deer had specific neutralizing antibody to trivittatus or La Crosse/snowshoe hare viruses at this study site. In 1984 and 1985, 78% and 63% of the adult does respectively exhibited significant anamnestic responses; all 19 adult does sampled over two seasons (between October 1983 and June 1985) showed a significant anamnestic response during at least 1 of the 2 yr. One-third of adult does with significant springtime antibody titer increases apparently experienced reexposure prior to the emergence of aedine mosquitoes, suggesting an alternate vector may overwinter at this site and transmit viruses in early spring. Specific neutralizing antibody was detected in 98% (66/67) of nursing fawns bled within 5 wk of birth in May-June 1984 and 1985, including three of three nursing fawns bled within 24-96 hr of birth. Of the 66 newborn fawns with specific neutralizing antibody to JC virus in June 1984 and 1985, 95% (54/57) of the surviving fawns lost maternal antibody and had no measurable titer when sampled 20-24 wk after birth, however. Serum antibody titers in 25 newborn (1984-cohort) fawns and their mothers and titers in 38 newborn (1985-cohort) fawns and their mothers were significantly correlated at the 5% and 1% levels respectively, suggesting that maternal antibody rather than a naturally acquired infection was the source of immunity in these suckling fawns.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3102764 TI - Leads from the MMWR. PCB contamination of ceiling tiles in public buildings--New Jersey. PMID- 3102765 TI - Hypokalemic respiratory arrest in diabetic ketoacidosis. PMID- 3102766 TI - Leads from the MMWR. Penicillinase-producing Neisseria gonorrhoeae--United States, 1986. PMID- 3102767 TI - Thickness unto death? PMID- 3102768 TI - The financial incentive for hospitals to prevent nosocomial infections under the prospective payment system. An empirical determination from a nationally representative sample. AB - To clarify the financial incentives for hospitals to prevent nosocomial infections, we analyzed 9423 nosocomial infections identified in 169 526 admissions selected randomly from the adult admissions to a random sample of US hospitals. By classifying each admission into a baseline diagnosis related group (DRG) (after first excluding all diagnoses of nosocomial infection) and a final DRG (after including these diagnoses), we found that only 5% to 18% of nosocomial infections would have caused the admission to be reclassified to a higher-paying DRG, depending on the extent to which physicians recorded nosocomial infection diagnoses in patients' medical records. The extra payment from the reclassification, averaged over all nosocomial infections, would have been no more than $93 per infection (in 1985 reimbursement rates), constituting only 5% of the hospitals' costs for treating these infections. Thus, at least 95% of the cost savings obtained from preventing nosocomial infections represents financial gains to the hospital. PMID- 3102769 TI - The effect of route of nutrient administration on the nutritional state, catabolic hormone secretion, and gut mucosal integrity after burn injury. AB - So that the efficacy of route of nutrient administration in thermal injury could be determined, a comparison was made between immediate enteral vs parenteral feedings in burned guinea pigs. Thirty-five guinea pigs underwent both catheter gastrostomy and jugular vein catheterization. On postoperative day 8, burned animals [30% total body surface area (TBSA)] were divided into an intragastrically (ig) fed group (N = 14) and a parenterally (iv) fed group (N = 14). Animals in each group received 175 kcal/kg/day with a solution of identical nutrient value beginning 2 hr after burn. The body weight change until postburn day (PBD) 8 and the average nitrogen balance were significantly better in the ig group than in the iv group. Values were also higher for the iv group than for the ig group in the early postburn period for urinary vanillyl mandelic acid (VMA) (p less than 0.05), plasma cortisol (p less than 0.05), and plasma glucagon (p less than 0.05). Also, the iv group showed reduced mucosal weight and thickness compared to the ig group on PBD 1 (p less than 0.02). There were significant negative correlations between VMA excretion and body weight change, and between plasma cortisol and jejunal mucosal structure (thickness and weight). These findings suggest that immediate postburn enteral nutrition can provide better nutritional support than parenteral nutrition through the maintenance of gut mucosal integrity and the prevention of increased secretion of catabolic hormones. PMID- 3102770 TI - Oral anticoagulant therapy in patients who require nutritional support. PMID- 3102771 TI - Serum cobalamin concentrations during TPN. PMID- 3102772 TI - Carbon dioxide production and respiratory quotient. PMID- 3102773 TI - Intact protein vs free amino acids in the nutritional support of thermally injured animals. PMID- 3102774 TI - Calcium loss with TPN. PMID- 3102775 TI - Energy expenditure and motor activity in rats receiving total parenteral nutrition. AB - Rats with intravascular catheters connected to infusion systems are frequently used in the investigation of nutritional and metabolic problems. Although the animal is often referred to as "unrestrained," there is no information on the effect of the catheter assembly or total parenteral nutrition (TPN) on total (TEE), activity (AEE), and resting (REE) energy expenditure (TEE = REE + AEE). Male Fischer 344 rats were studied in an analytical respiration calorimeter. Normal unoperated rats, aseptically catheterized orally fed rats from postoperative day 1 to 7, and TPN rats were studied. Orally fed catheterized rats had weight loss, negative nitrogen balance, negative energy balance, elevated REE, and normal AEE during the first 4 postoperative days. Their weight gain, positive nitrogen balance, AEE, and REE were almost identical to those of normal rats over postoperative days 5 through 7. REE and AEE in TPN rats were similar to values in normal rats. These data indicate that catheter operation and TPN cause no abnormality in AEE and REE if adequate time is allowed for recovery from catheter operation and strict attention is given to asepsis. PMID- 3102776 TI - Nutritional effectors of hepatic steatosis induced by parenteral nutrition in the rat. AB - The relative importance of three nutritional variables, nonprotein energy level, glucose-lipid calorie distribution and amino acid nitrogen level, in contributing to the steatosis that develops during a short course of parenteral nutrition was studied in intravenously fed rats. Eight infusates were tested that contained various combinations of glucose, lipid emulsion and amino acids. The infusate nonprotein energy level was the predominant effector of liver lipid content. The excessive energy level was associated with significant increments in steatosis, ranging from a 26% increase for high-fat, adequate-nitrogen infusates to a 95% increase for low-fat, adequate-nitrogen infusates. An interaction of amino nitrogen level and glucose-lipid calorie distribution also affected the severity of steatosis. The steatosis observed with inadequate-nitrogen infusates was accentuated in combination with the high-fat calorie distribution and was attenuated with the low-fat calorie distribution. The most striking effect of nitrogen inadequacy was a 3-fold increase in liver lipid content with the excessive calorie, high-fat infusates. The infusate that minimized steatosis provided energy and nitrogen at adequate levels and was low in fat content. This infusate also led to liver lipid composition and plasma lipid levels that most closely resembled those of rats fed stock diet. PMID- 3102777 TI - Parenteral infusion with an admixture of amino acids, dextrose, and fat emulsion solution: compatibility and clinical safety. AB - Fat emulsions are increasingly utilized as intravenous calorie sources in patients requiring total parenteral nutrition. In the United States, they are traditionally administered separate from the dextrose/amino acid solution because of concern regarding physical stability and clinical safety when fat emulsions are administered, having been mixed with the dextrose solution. The separate infusion entails multiple manipulations of the infusion system with increased risk of contamination and sepsis and increased cost in maintaining two infusion lines. This prospective sequential two-phase clinical study evaluated solution compatibility and clinical safety of an admixture of fat emulsion (Intralipid 20%), dextrose, amino acids (Veinamine 8%), electrolytes, vitamins, and trace minerals. Continuous infusion of this solution in 25 adult patients from 2 to 35 days did not result in any adverse clinical reactions or abnormal laboratory parameters. Gross, visual examination and in vitro analysis of the admixture solutions revealed no physical instability or changes in fatty acid composition in admixture solutions stored at 4 degrees C for up to 6 weeks. PMID- 3102778 TI - The effect of the route of nutrient delivery on gut structure and diamine oxidase levels. AB - Diamine oxidase (DAO) is an intestinal mucosal enzyme which serves as a marker of cellular maturity and integrity in ontogeny and after mucosal injury in the gastrointestinal tract. Since total parenteral nutrition is known to result in intestinal hypoplasia, this study was done to determine the effect of enteral and parenteral delivery of nutrients on gut structure and DAO levels. Central venous catheters were placed in 27 Sprague-Dawley rats (180-260 g), which received nutrients for 12 days via parenteral nutrition (GpI n = 10), oral intake of the parenteral solution (GpII n = 8), or standard rat chow (GpIII n = 9). Gross and microscopic measurements were made at sacrifice. Mucosal DAO levels were determined by metabolism of [3H] putrescine. Group III animals had a greater caloric intake than groups I and II, and were the only group with a significant increase in body weight. Gut weight, mucosal weight, and villous height were significantly less in group I vs groups II and III; group II values were less than group III (p less than 0.05). Both DAO specific activity and total gut DAO were significantly less in group I and group II. Mucosal DAO content correlated with total gut and mucosal weight. DAO mucosal levels decrease with parenteral nutrition, reflecting the intestinal hypoplasia that occurs. Mucosal DAO content may be dependent on both caloric intake and diet composition. Since serum DAO levels are known to correlate with mucosal DAO content, DAO activity may prove useful as a circulating marker of the effect of nutritional therapy on the intestinal mucosa. PMID- 3102779 TI - Efficacy of metoclopramide as an adjunct to duodenal placement of small-bore feeding tubes: a randomized, placebo-controlled, double-blind study. AB - We examined whether metoclopramide would improve the success rate of transpyloric intubation of a weighted Corpak feeding tube when fluoroscopic guidance is not used. Seventy patients were randomized in a prospective, double-blind fashion to receive either placebo (n = 35) or metoclopramide, 10 mg (n = 35) parenterally, administered immediately after the feeding tube was inserted. Tube location was determined independently by two observers who examined radiographs obtained after barium was instilled via the tube. There was no significant increase in the success rate of duodenal intubation in the total group following metoclopramide, 60%, compared to placebo, 49%. However, analysis of subgroups among the placebo treated patients revealed that diabetes mellitus, but not other medical conditions, decreased the success rate for duodenal intubation, 20 vs 60% (p less than 0.05). Among diabetic patients, metoclopramide resulted in a significant increase in duodenal placement compared to placebo (p less than 0.05). We conclude that parenteral metoclopramide significantly increases the frequency of transpyloric intubation with small feeding tubes without fluoroscopic guidance in diabetic patients but not in nondiabetic patients. PMID- 3102780 TI - The incidence and clinical significance of intravenous fat emulsion contamination during infusion. AB - So that the actual contamination rate of intravenous fat emulsions, as well as the type of microbial contamination, could be quantified, 103 bottles of 10% fat emulsion were collected near infusion completion from patients' bedsides. All samples were cultured and compared according to actual hanging time, in addition to the amount and type of microbial contamination. Recovered organisms included Escherichia coli, Staphylococcus epidermidis, diphtheroids, and Micrococcus. Sample analysis failed to demonstrate significant differences in extrinsic microbial contamination rate or organism multiplication between samples infusing for less than or equal to 12 hr and those infusing longer. Although these products support microbial growth, the contaminants introduced into the infusate by environmental or touch contamination yielded minimal colony growth. No patient developed signs or symptoms of bacteremia during the study period. Therefore, infusion of intravenous fat emulsion products over extended periods of time in this study did not increase the risk of developing infectious complications. PMID- 3102781 TI - The influence of intravenous medium- and long-chain triglycerides and carnitine on the excretion of dicarboxylic acids. AB - Four groups of male Wistar rats were alimented parenterally for 3 days. Groups 1 and 2 received medium-chain triglycerides (MCT) and groups 3 and 4 long-chain triglycerides (LCT). Groups 2 and 4 were supplemented with 100 mg L carnitine/kg/day. The MCT-alimented rats presented with a distinct excretion of the dicarboxylic acids: adipic acid (C6), suberic acid (C8), and sebacic acid (C10). The acids excreted corresponded to the infused pattern of monocarboxylic acids: caproic acid (C6), caprylic acid (C8), and capric acid (C10). Dicarboxylic acid excretion after MCT administration may reflect an insufficient capacity of beta-oxidation on one hand or a preferential omega-oxidation of medium-chain fatty acids on the other. Carnitine supplementation lead to a further increase of the dicarboxylic acids in the MCT-group. beta-OH-butyric acid excretion decreased after carnitine in the MCT as well as in the LCT group. An increased transport of fatty acid-carnitine compounds out of the mitochondria is discussed as an important effect of carnitine supplementation. Hereby medium-chain fatty acids may be more accessible for omega-oxidation. PMID- 3102782 TI - Impact of nutritional status on DRG length of stay. AB - A prospective audit of 100 admissions to a general medical unit was performed to determine the relationship of the initial nutritional status of the patients to the actual length of stay and hospital charges. These data then were compared with the allowed length of stay and estimated reimbursement under the prospective payment system of diagnosis-related groups (DRGs). Forty-five percent of the malnourished patients were hospitalized longer than that allowed under DRGs, compared to 30% for normal patients and 37% in the borderline group. The average length of stay was 15.6 +/- 2.2 days in the malnourished group compared to approximately 10 days in the other two groups (p less than 0.01). Although the estimated base DRG reimbursement was similar in all three groups ($4352-$5124), the actual hospital charges were significantly greater in the malnourished ($16,691 +/- 4389) and borderline ($14,118 +/- 4962) groups compared to normals ($7692 +/- 687), (p less than 0.01). The DRG system will have an adverse financial impact in the care of malnourished patients. It is suggested that early recognition of malnutrition and aggressive treatment may lead to a decrease in the length of stay and cost deficit incurred by malnourished patients. PMID- 3102783 TI - Enteral nutritional support management in a university teaching hospital: team vs nonteam. AB - Current hospital cost containment pressures have prompted a critical evaluation of whether nutritional support teams render more clinically effective and efficient patient care than nonteam management. To address this question with regard to enteral feeding, 102 consecutive hospitalized patients who required enteral nutritional support (ENS) by tube feeding during a 3 1/2-month period were prospectively studied. Fifty patients were managed by a nutritional support team; the other 52 were managed by their primary physicians. Choice of enteral formula, formula modifications, frequency of laboratory tests, and amounts of energy and protein received were recorded daily. In addition, each patient was monitored for pulmonary, mechanical, gastrointestinal, and metabolic abnormalities. Team-managed (T) and nonteam-managed (NT) patients received ENS for 632 and 398 days, respectively. The average time period for ENS was significantly longer in the team-managed patients (12.6 +/- 12.1 days vs 7.7 +/- 6.2 days, p less than 0.01). Significantly more of the team patients attained 1.2 X basal energy expenditure (BEE) (37 vs 26, p less than 0.05). Total number of abnormalities in each group was similar (T = 398, NT = 390); however, the abnormalities per day were significantly lower in the team group (T = 0.63 vs NT = 0.98, p less than 0.01). Mechanical (T = 0.05 vs NT = 0.11, p less than 0.01), gastrointestinal (T = 0.99 vs NT = 0.14, p less than 0.05), and metabolic (T = 0.49 vs NT = 0.72, p less than 0.01) abnormalities per day all were significantly lower in the team-managed patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102784 TI - Total parenteral nutrition-associated cholestasis in rats: comparison of different amino acid mixtures. AB - It has been suggested that the quantity of amino acids perfused is a pathogenetic factor in total parenteral nutrition (TPN)-associated hepatotoxicity. However, the effect of the qualitative pattern of amino acid solutions has not been studied. Rats on parenteral nutrition for 5 days received 10.2 g of dextrose and 3.4 g of amino acids daily. Bile flow (microliter/min/g liver protein) after administration of Vamin was 16.2 +/- 0.8, which was similar to that in controls given chow and dextrose iv, but it was significantly higher (p less than 0.001) than those on Travasol (12.3 +/- 0.8). The decrease in bile flow was not related to the large concentrations of alanine and glycine present in Travasol. However, the addition to Travasol of serine present only in Vamin increased bile flow significantly. Bile acid secretion rate, biliary lipid constituents, calcium, sodium, and glucose showed little change. In contrast, alpha-amino nitrogen was increased (p less than 0.05) in Vamin-perfused animals. Steatosis was noted in only a few animals in the Travasol group, and was not associated with an increase in the triglycerides content of the liver. Glycogen and protein content of the livers did not differ. The data show that the composition of amino acid solutions may be a determinant of TPN-induced cholestasis and suggest that the presence of methyl donor amino acids may have a protective effect. PMID- 3102785 TI - A rapid, accurate, precise assay for determination of plasma transferrin. AB - Plasma transferrin (TFN) levels are valid as markers of protein-calorie malnutrition (PCM). Current methods for determining TFN, specifically, radial immunodiffusion (RID) plates or derivation from total iron-binding capacity (TIBC), are relatively expensive, time consuming (20-50 hr) and technically demanding, limiting the use of TFN levels in the routine screening for PCM. A rapid (60-90 min), accurate and precise TFN assay, easily performed with common laboratory equipment, was developed for use in a study of hospitalized patients. This assay requires 15 microliter of plasma and is based on an antigen-antibody reaction using commercially available TFN antibody. After a 30-min incubation, turbidity is measured at 413 nm on a spectrophotometer with a 1-cm path length. Values by this method are linear over the range of 50-760 mg/dl. Plasma samples (n = 72) were assayed for TFN by this turbidimetric (TURB) technique and the standard RID technique. Correlation between the two assays was r = 0.942 over the range of TFN = 81-403 mg/dl (TFNRID = 30.7 + (0.931) TFNTURB). Coefficient of variation (CV) for TFNTURB was 4.0%. RID kit insert reports a CV = 2.9% at a value of 380 mg/dl. This assay overcomes many of the difficulties associated with TFN determination by RID or derived from TIBC and may allow more widespread application of plasma TFN levels as a clinically relevant PCM screening tool. PMID- 3102786 TI - Improvement of liver function tests by administration of L-carnitine to a carnitine-deficient patient receiving home parenteral nutrition: a case report. PMID- 3102787 TI - Total parenteral nutrition in pregnancy complicated by Crohn's disease. AB - Despite the widespread use of total parenteral nutrition (TPN) in nonpregnant patients, the literature reflects limited experience with TPN in pregnancy. However, since maternal nutritional deprivation may cause adverse fetal effects, its use appears warranted. We present a case of a pregnant patient with a poor reproductive history and recently diagnosed Crohn's disease who required TPN. We discuss the use of TPN with fat emulsions in this patient who was unable to tolerate enteral feedings during pregnancy. The patient underwent a 4-week period without oral intake. Total parenteral nutrition enabled continued fetal growth, resulting in a good outcome for the patient and her infant. This report supports the early use of TPN in pregnancy complicated by inadequate caloric intake. PMID- 3102788 TI - Use of separate insulin infusions with total parenteral nutrition. AB - The efficacy, safety, and cost effectiveness of treating total parenteral nutrition (TPN)-induced hyperglycemia with a continuous insulin infusion, separate from the actual TPN bottle, was evaluated. A patient was included in the study if his serum glucose was greater than 200 mg/dl at a TPN infusion rate of less than 75% of the calculated caloric goal. The insulin infusion was run into the central line with the TPN via a Y-connector. At the patient's caloric goal, the infusion was stopped and the insulin was added to the TPN bottle, after the glucose was in the 100-200 mg/dl range for 24 hr. Sixteen patients including five known diabetics were studied, with data gathered retrospectively through chart review. It was estimated that 7.3 liters of TPN per patient were saved, compared to the amount used when insulin was added to newly prepared bottles of TPN each time a dosage change was required. In our institution, this amounts to a savings of $395.00 per patient (including charges for materials and an infusion pump for the insulin infusion). We conclude that separate insulin infusion is a reasonable and cost-effective alternative when treating glucose intolerance in patients receiving TPN. PMID- 3102789 TI - A.S.P.E.N.'s (American Society for Parenteral and Enteral Nutrition) 11th clinical congress. Abstracts. PMID- 3102790 TI - Hepatitis "A"--new developments. PMID- 3102791 TI - Childhood asthma, response to oral prophylaxis. PMID- 3102792 TI - Morphological and chemical study of urinary calculi. PMID- 3102793 TI - Food hygiene with reference to public health. Viable bacterial counts of ready to eat foods served in Rawalpindi Islamabad. PMID- 3102794 TI - Genital prolapse in the new born. PMID- 3102795 TI - Erythrocyte sedimentation rate. PMID- 3102796 TI - History and clinical practice of modern blood transfusion therapy: a review. PMID- 3102797 TI - Psychiatric disorders in general practice. PMID- 3102798 TI - Radiometric detection of bacterial growth in breath cultures. PMID- 3102799 TI - Prevalence of anti rubella antibodies in pregnant and prepubertal females--a preliminary study. PMID- 3102800 TI - Distribution of ABO and Rh blood groups in the residents of Bahawalpur. PMID- 3102801 TI - Eosinophilic gastritis. PMID- 3102802 TI - Effect of OKY-046, a thromboxane A2 synthetase inhibitor, on arachidonate-induced platelet aggregation: possible role of "prostaglandin H2 steal" mechanism. AB - To clarify the mode of action of a selective thromboxane A2 (TXA2) blockade in platelet reactivity, we examined the effect of (E)-3-[4-(1-imidazolylmethyl) phenyl]-2-propenoic acid hydrochloride (OKY-046), a potent TXA2 synthetase inhibitor, on human platelet aggregation induced by arachidonic acid (1 mM) in the absence and presence of aspirin-treated aortic microsomes containing prostacyclin (PGI2) synthetase activity ex vivo. The production of TXA2 and PGI2 in platelet rich plasma was determined by the amounts of their stable catabolites, TXB2 and 6-keto-PGF1 alpha respectively, measured by radioimmunoassay. In the absence of aortic microsomes, OKY-046 (greater than 10( 5) M) produced more than 90% inhibition of TXA2 production, whereas platelet aggregation was less inhibited, about 40% inhibition over control, by OKY-046 in that concentration. In the presence of aortic microsomes, the inhibitory effect of OKY-046 on platelet aggregation was markedly augmented in a dose-dependent manner in proportion to the increment of PGI2 production, which paralleled the OKY-046-induced inhibition of TXA2. These results suggest that a selective TXA2 blockade produces effects on platelet aggregation mainly in dual fashion in the presence of PGI2 synthetase: one is due to mere inhibition of TXA2 synthetase and the other is due to the enhancement of PGI2 production probably involving "prostaglandin H2 (PGH2) steal" mechanism, in which PGH2 accumulated in platelets is partly converted to a substrate of PGI2 synthetase in aortic microsomes to produce PGI2. PMID- 3102803 TI - The false positive exercise test: usefulness of sublingual nitroglycerin exercise test and cardiac scintigraphy for differentiating from patients with coronary artery disease. AB - Exercise tests with sublingual nitroglycerin were performed on 7 patients with true positive and 8 patients with false positive exercise test results. Four of 7 patients with true positive changes and 8 patients with false positive changes underwent exercise cardiac scintigraphy. Scintigrams showed perfusion defects in 4 patients with true positive outcomes, and no perfusion defect in 8 patients with false positive outcomes. Exercise tests with sublingual nitroglycerin were performed with the same load as that without nitroglycerin. In all 7 patients with true positive exercise test results, ST segment depression observed in the control exercise test was not observed in the nitroglycerin exercise test. In the false positive patients, ST segment depression observed in the control exercise test remained unchanged in 7 of 8 patients receiving nitroglycerin. Exercise tests with sublingual nitroglycerin as well as exercise cardiac scintigraphy are valuable tods in differentiating false positive from true positive patients. Furthermore, these data suggest that ST segment depression in the false positive patients may not be related to myocardial ischemia. PMID- 3102804 TI - Attenuated development of hypertension by chronic administration of bromocriptine in Doca-salt hypertensive rats. AB - The aim of the study was to investigate whether or not the development of hypertension is influenced by chronic treatment with bromocriptine and/or domperidone. Rats treated with DOCA-salt were divided into 4 groups: control with vehicle, bromocriptine, bromocriptine with domperidone, and domperidone. Increased blood pressure by DOCA-salt treatment was significantly suppressed by treatment with bromocriptine and this bromocriptine suppression was significantly blocked by treatment with domperidone. Increased urinary excretion of norepinephrine by DOCA-salt treatment was significantly suppressed by bromocriptine and the inhibiting effect of bromocriptine disappeared with domperidone. In the four groups of rats, there were significant correlations between systolic blood pressure and urinary excretion of norepinephrine, systolic blood pressure and urinary excretion of epinephrine, and urinary excretion of dopamine and sodium. These results suggest that the chronic effect of bromocriptine is to suppress development of DOCA-salt hypertension, mainly through peripheral mechanisms which are involved in the decreased release of norepinephrine. PMID- 3102805 TI - [Cardiovascular changes during hypotensive anesthesia--a comparison of trimethaphan, glyceryl trinitrate and ATP]. PMID- 3102806 TI - [New antimicrobial agent series XVII: Ceftazidime]. PMID- 3102807 TI - [Clinical evaluation of astromicin administered by intravenous drip infusion. Report III. Bacterial infections in the field of urology]. AB - Intravenous drip infusion of a new aminoglycoside agent, astromicin (ASTM), was used for various urological infections, and its clinical efficacy and safety were studied. Each of almost all the patients tested was given 200 mg of ASTM twice a day by intravenous drip infusion. Among 114 cases with complicated urinary tract infections (UTI) evaluated according to the criteria for evaluation of drug efficacy in UTI, clinical response was excellent in 16, moderate in 54 and poor in 44. The efficacy rate was 61.4%. Among 137 cases who were evaluated for side effects, headache was observed in 1 case (0.7%), which recovered spontaneously the day after the withdrawal of the drug. Slight elevation in S-GOT, S-GPT, Al-P and others was observed in 12 cases (8.8%) as abnormal laboratory test values. PMID- 3102808 TI - [Comparative studies of antimicrobial agents against causative organisms isolated from urinary tract infections (1984). I. Susceptibility distribution]. AB - Our research group was engaged for 3 years (1979-1981) in a study on sensitivities to antibiotics of 4 bacterial groups including representative pathogenic bacteria found in cases of urinary tract infections; i.e. E. coli, Klebsiella spp., Citrobacter spp., and Proteus spp. Since 1982, all the bacterial strains isolated by our group from patients with urinary tract infections and deemed by doctors in charge as pathogens were sent to the Laboratory of Clinical Pathology of Juntendo University, where they were refixed and subjected to MIC determination. This is the third year of the new study. E. coli was detected most frequently from patients with urinary tract infections and the detection frequency was 28% (323/1,153) this year (1984), whereas it was 35.3% (304/860) last year, showing a 7% decline from last year to this year. E. faecalis was next frequent organism (12.7% or 147/1,153) followed by P. aeruginosa (10.8% or 124/1,153). This order, however, was reversed from last year. Other pathogens, in a decreasing order of isolation frequencies following the above three, were as follows: Proteus spp. (9.5% or 109/1,153), S. marcescens (6.2% or 71/1,153), S. epidermidis (5.4% or 62/1,153), K. pneumoniae (4.9% or 56/1,153), Enterobacter spp. (2.4% or 28/1,153) and Citrobacter spp. (2.3% or 27/1,153). The results of the determination of the sensitivity of bacterial strains to the antibiotics are described below. Of all the oral antibacterial and antibiotic agents used against E. coli, mecillinam (MPC), cefaclor (CCL) and pipemidic acid (PPA) proved to have high antibacterial potency, and their MIC90 (the concentration to inhibit growths of 90% of the objective bacteria) was 3.13 micrograms/ml. The MIC90's of cefotiam (CTM), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX) and latamoxef (LMOX) were less than 0.39 microgram/ml. The MIC90's of cefmetazole (CMZ) and cefoperazone (CPZ) were invariably 1.56 micrograms/ml. K. pneumoniae was not sensitive to ampicillin (ABPC) and did not show much sensitivity to other oral antibacterial and antibiotic agents also. Of all the injectable preparations of antibiotics, cephem antibiotics of the third generation showed the most potent antibacterial effects against K. pneumoniae, and their MIC90's were lower than 0.10 microgram/ml for CZX, 0.20 microgram/ml for CTX, 0.39 microgram/ml for CMX, and 0.78 microgram/ml for LMOX, while MIC90's of CPZ was 6.25 micrograms/ml, which was equal to that of CMZ. The MIC90 of CTM was 0.78 microgram/ml which was identical to that of LMOX.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3102809 TI - [Comparative studies of antimicrobial agents against causative organisms isolated from urinary tract infections (1984). III. Secular changes in susceptibility]. AB - Cases with infections of urinary tracts were divided into 3 groups of the simple infections, and complicated infections without indwelling of catheter, and complicated infections with indwelling of catheter. Susceptibilities to antimicrobial agents of Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Pseudomonas aeruginosa and Serratia marcescens which were isolated from patients with these infections were determined. There was no tendency of decline in the susceptibilities of E. coli isolated from the patients with simple urinary tract infections (UTI). Susceptibilities of E. coli isolated from the patients with complicated UTI without and with indwelling of catheter to cephem antibiotics of the third generation were examined. The susceptibility of E. coli strains isolated from patients with complicated UTI without and with indwelling of catheter remained the same. More specifically, cefmenoxime (CMX) at a concentration of less than 0.10 microgram/ml inhibited the growth of E. coli isolated from cases without: with catheter at 74.1%: 78.3% in 1982, 75.4%: 73.3% in 1983, and 81.3%: 84.8% in 1984. Also, ceftizoxime (CZX) at a concentration of less than 0.10 microgram/ml inhibited the growth at 83.3%: 95.7% in 1982, 89.2%: 86.7% in 1983, and 91.7%: 97.0% in 1984. Latamoxef (LMOX) at less than 0.10 microgram/ml inhibited the growth at 59.3%: 43.5% in 1982, 47.7%: 40.0% in 1983, and 47.9%: 42.4% in 1984. The antibacterial effect of penicillin against Klebsiella spp. was found to be poor, while those of oral cephem antibiotics, cephalexin (CEX), cefaclor (CCL), and cefazolin (CEZ) which is the cephem antibiotics of the so-called first generation and cefotiam (CTM) among other cephem antibiotics of the so-called second generation were relatively good. A study of susceptibilities of Klebsiella spp. isolated from patients with complicated UTI without and with indwelling of catheter revealed inhibition of growth by CTM at a concentration of 0.39 microgram/ml at 84.0%: 75.9% in 1982, 70.6%: 75.0% in 1983, and 95.8%: 77.8% in 1984. Cefmetazole (CMZ) at a concentration of 0.39 microgram/ml showed a relatively lower rate of growth inhibition of Klebsiella spp., while at 0.78 microgram/ml it inhibited the growth at 88.0%: 72.4% in 1982, 52.9%: 50.0% in 1983, and 70.8%: 66.7% in 1984. The antibacterial effects of both CTM and CMZ against Klebsiella spp. isolated from patients with indwelling of catheter were found to be poor, and some of the bacterial strains showed a MIC over than 100 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3102810 TI - [Metastatic brain tumor after chemotherapy of ovarian cancer]. AB - A case of brain metastasis in ovarian cancer is reported. Recently cis platin containing combination chemotherapeutic regimens have improved the prognosis of patients with advanced ovarian carcinoma. Metastasis to the brain in ovarian cancer is very rare. However, the incidence of cerebral metastasis after chemotherapy for ovarian carcinoma seems to be increasing, and this may be related to prolonged survival due to chemotherapy. Thus, neurological examination after chemotherapy with cis platin is necessary to detect metastases to the brain. PMID- 3102811 TI - [Intra-arterial infusion chemotherapy for poor-risk patients with locally advanced bladder cancer--clinical assessment of five cases]. AB - One-shot infusion of anticancer agents via the ligated internal iliac artery after urinary diversion was performed repeatedly in five patients with locally advanced bladder cancer in whom total cystectomy was contraindicated. Drugs infused were adriamycin and/or mitomycin C. Other combination treatments were undertaken before and after this strategy. They included radiation, oral chemotherapy and intravesical instillation of anticancer agents. Adverse reactions did not seem to be clinically significant. Complications were intractable fever, obstruction of the cannula, and prostration, resulting in interruption and discontinuity of this strategy within 11 weeks (in all cases). As a result, PR was achieved in two cases, MR in two, and PD in one according to Koyama-Saito's criteria. This strategy seemed to be promising and effective for locally advanced bladder cancer. PMID- 3102812 TI - [Studies on platelets in a patient with a novel hereditary platelet function disorder--impaired aggregation in response to A 23187 with normal response to arachidonic acid]. PMID- 3102813 TI - [IgG producing follicular lymphoma with IgG lambda type M-proteinemia; a case report]. PMID- 3102814 TI - [Two cases of red cell aplasia with multiple immunological abnormalities developing after resection of thymoma]. PMID- 3102815 TI - [Recent trend in pathogenic bacteria of urinary tract infections--simple and complicated urinary tract infections]. PMID- 3102816 TI - [Rapid diagnosis of bacterial infection by detecting antigens]. PMID- 3102817 TI - Antitumor effect of human necrosis factor on human hepatoma cells PLC/PRF/5. AB - The antitumor activity of natural human tumor necrosis factor (TNF) on a human hepatoma cell line PLC/PRF/5 was studied in vitro. TNF produced by the LuKII human lymphoblastoid cell line showed a cytostatic effect on the hepatoma cells, whereas the growth of non-tumorigenic Chang liver cells was little affected. The combined effects of TNF and interferon-gamma (IFN-gamma) were additive on the PLC/PRF/5 cells as shown by statistical analyses. The same combination showed synergistic effects on a human breast cancer cell line BT-20, which was highly sensitive to TNF. These data may provide some informations concerning the use of TNF in the treatment of hepatoma. PMID- 3102818 TI - [A case report of Crohn's disease maintained on parenteral nutrition for almost the whole period of pregnancy]. PMID- 3102820 TI - [Development of the Rh blood groups]. PMID- 3102819 TI - [A case of chronic intestinal pseudo-obstruction complicated by mucopolysaccharidosis I Scheie type]. PMID- 3102821 TI - [Development of the H2(15)O continuous infusion system and its clinical application for the measurement of regional cerebral blood flow with special reference to the cerebral blood flow reactivity to hypercapnia]. PMID- 3102822 TI - Radionuclide study on hepatic blood flow in schistosomiasis japonica. PMID- 3102823 TI - Pharmacological studies on proglumetacin maleate, a new non-steroidal anti inflammatory drug (4). Mode of action on anti-inflammatory activity. AB - The possible mechanism of the anti-inflammatory activity of proglumetacin maleate (PGM), a new indomethacin (IND) derivative interacting with arachidonic acid (AA) metabolism, was investigated to elucidate the contributions of PGM itself and its two major metabolites, desproglumideproglumetacin maleate (DPP) and IND. PGM caused much less inhibition of PGE2 formation by sheep seminal vesicle microsomes (IC50 = 310 microM) and TXB2 formation by a washed rabbit platelet suspension (IC50 = 6.3 microM) than IND. DPP also caused less inhibition of cyclooxygenase than IND. Moreover, PGM had less effect on sodium arachidonate (SAA)-induced rat platelet aggregation ex vivo and AA-induced sudden death in rabbits than IND. These results show that PGM has anti-inflammatory activity after its conversion to the active metabolite IND. However, the inhibitory effects of PGM and DPP were as strong as that of IND on SAA- or collagen-induced rabbit platelet aggregation in vitro. These activities are considered to be associated with platelet membrane interaction. Moreover, unlike IND, PGM (IC50 = 1.5 microM) and DPP (IC50 = 16.3 microM) strongly inhibited 5-HETE formation by the cytosol of guinea pig polymorphonuclear leukocytes. This unique activity of PGM on 5-lipoxygenase may contribute to its anti-inflammatory activity. PMID- 3102824 TI - [Two cases of tracheobronchopathia osteoplastica]. PMID- 3102825 TI - Sarcocystis miescheriana infection and its frequency in pigs in Japan. PMID- 3102826 TI - In vivo distribution of recombinant interleukin-2-activated autologous lymphocytes administered by intra-arterial infusion in patients with renal cell carcinoma. AB - Recombinant interleukin-2 (RIL 2)-activated autologous peripheral blood lymphocytes (PBL) were infused directly into the renal arteries of 3 patients with renal cell carcinoma, and the in vivo distribution of the infused cells was investigated. In vitro studies to define the optimal culture conditions indicated that maximal lymphokine-activated killer activity was observed at around 10-20 days in culture, as judged by the cytotoxicity against fresh allogenic tumor cells. Maximal expression of the interleukin-2 receptor was also obtained at around 10 days. PBL collected by leukopheresis from each patient were thus cultured for 10 days with RIL 2, labeled with 111In-oxine, and then infused directly into the renal artery of the affected kidney via a catheter. Radioactivity in the infused side of the kidneys increased immediately after the infusion but then gradually decreased. Radioactivity in the lungs also rapidly increased within the first hour but then cleared gradually, whereas that in the liver and spleen tended to increase steadily. Nevertheless, at 48 hours, the infused side of the kidneys retained levels of radioactivity comparable to those seen in the liver and spleen, while the levels seen in the lungs were already close to background levels. The radioactivity in the areas corresponding to tumors remained consistently higher than that in the normal parts of the affected kidneys. The direct comparison of the radioactivity distribution pattern with the macroscopic appearance of surgically resected kidneys indicated that the accumulation of radioactivity was indeed selectively associated with the tumor tissues in the kidneys, except for a case in which the tumor was quite necrotic and hypovascular. Histological examinations indicated intensive mononuclear cell infiltrations in and around the tumor tissues as well as in normal tissues in the kidneys. These preliminary results indicated that infusion of activated lymphocytes via major tumor-feeding arteries would be an extremely effective way to obtain the selective localization of effector cells in the tumor tissues. PMID- 3102827 TI - Normal but not carcinomatous primary rat mammary epithelium: readily transplanted to and maintained in the athymic nude mouse. AB - Transplantation success rates of primary 7,12-dimethylbenz(a)anthracene [(DMBA) CAS: 57-97-6]-induced rat mammary carcinomas and normal rat mammary glandular epithelium into female athymic mice were compared. The rat mammary carcinomas obtained from female Sprague-Dawley rats were transplanted into host athymic mice (6-8 wk of age) as 1 x 1-cm slices xenografted sc (2 slices/mouse) or as enzymatically dissociated cells inoculated into the gland-free mammary fat pad. Normal rat mammary glands (No. 4 glands and 3- to 5-mo-old virgin rats) were transplanted into host athymic mice as whole, intact mammary glands sc (1 gland/mouse) or as enzymatically dissociated cells inoculated into the gland-free mammary fat pad. All (100%) of the normal rat mammary glands were readily accepted and maintained in the athymic mice when transplanted either sc as whole glands or as dispersed cells inoculated into the gland-free fat pad. In contrast, only 13-14% of the DMBA-induced rat mammary carcinomas were accepted and maintained in the athymic mice (transplanted as slices sc or as dispersed cells inoculated into the gland-free fat pad). Treatment of host athymic nude mice with an intense mammotropic hormonal stimulus (prolactin and/or ovarian steroids) markedly enhanced the developmental growth of the transplanted normal rat mammae (subcutaneous slices and fat-pad inoculates); such a hormonal stimulus did not influence the transplantation success rate of the DMBA-induced rat mammary carcinomas. Thus female athymic nude mice can readily accept and maintain transplants of normal rat mammae but not carcinogen-induced carcinomatous rat mammae; the meager acceptance rate of the carcinomatous rat mammae by the athymic nude mouse was not enhanced by providing the host mice with a potent mammotropic hormonal growth stimulant. PMID- 3102828 TI - Coordinately increased lysozymuria and lysosomal enzymuria induced by maleic acid. AB - During the acute renal tubular dysfunction of Fanconi syndrome and type 2 renal tubular acidosis (FS/RTA2) induced by maleic acid in the unanesthetized dog, we observed: 30 minutes after the onset of FS/RTA2, the urinary excretion of lysosomal enzymes, N-acetyl-beta-glucosaminidase (NAG), beta-glucuronidase (beta gluc) and beta-galactosidase (beta-galac), increased simultaneously with the anticipated increase in renal clearance of lysozyme; the severities of all these hyperenzymurias increased rapidly, progressively, and in parallel, all reaching a peak some 60 to 80 minutes after their onset; thereafter, while the FS/RTA2 continued undiminished in severity, the severity of the hyperenzymurias decreased rapidly, greatly, progressively, and in parallel; and sodium phosphate loading strikingly attenuated the FS/RTA2 and the hyperenzymurias. Thus, the maleic acid induced FS/RTA2 is attended by an acute reversible-complex derangement in the renal tubular processing of proteins that: affects not only lysozyme which is normally filtered, but also NAG and other lysosomal enzymes, which are not; and is to some extent functionally separable from that of FS/RTA2. The findings suggest that the derangements in renal processing of lysozyme and lysosomal enzymes are linked, and that a phosphate-dependent metabolic abnormality in the proximal tubule can participate in the pathogenesis of both these derangements and the FS/RTA2. PMID- 3102829 TI - [Current status of urogenital tuberculosis]. PMID- 3102831 TI - Long-term effects of nifedipine on plasma levels of 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D in hypertensive hemodialyzed patients. PMID- 3102830 TI - Myoadenylate deaminase deficiency: successful symptomatic therapy by high dose oral administration of ribose. AB - A 55 years old patient suffering from exercise-induced muscle pain and stiffness due to primary myoadenylate deaminase deficiency has been successfully treated with D-ribose since 1984: single doses of 4 grams administered at the beginning of exercise prevented the symptoms completely; on continuation of exercise this dose had to be repeated all 10-30 min. Total doses of 50-60 g per day were tolerated without side-effects. PMID- 3102832 TI - Effects of coadministered antiepileptic drugs on free fractions of phenobarbital and valproic acid in epileptic children. PMID- 3102833 TI - Characterization of transplant generations of primary rat adenocarcinomas. PMID- 3102834 TI - [1st continuing education in psychiatric nursing of the German Nursing Association. Intermediate results of the model course at the study center Essen]. PMID- 3102835 TI - ["Primary nursing care", how does it benefit us in Germany? Exchange of experiences at the Workgroup of European Nurse Researchers in Helsinki]. PMID- 3102836 TI - [Experiences with the nursing process]. PMID- 3102837 TI - [Practical experiences with the nursing process]. PMID- 3102838 TI - [Birth and death of a model experiment: education towards critical awareness in nursing. 1]. PMID- 3102839 TI - [Experiences in the execution of the nursing process on the ward]. PMID- 3102840 TI - [Attitude to the reactions of the nursing staff]. PMID- 3102842 TI - [Introduction of planned nursing--experiences, motivations]. PMID- 3102841 TI - [My attitude to the reactions of the nursing staff]. PMID- 3102843 TI - [Lower management in the hospital: duties, responsibilities, problems and risks]. PMID- 3102844 TI - [Birth and death of a model experiment: education towards critical awareness in nursing. 2]. PMID- 3102845 TI - [The ward manual--an aid to practical work on the ward?]. PMID- 3102846 TI - [Healthier living--nursing with more awareness. Care planning, nursing documentation, quality assurance--chances for nursing?/A view of the history of professional nursing]. PMID- 3102847 TI - [Health--a nursing paradigm and standard for the quality of care]. PMID- 3102848 TI - [Training in supervisory nursing--practical results]. PMID- 3102849 TI - [AIDS--occurrence and means of transmission. Nursing problems in practical care]. PMID- 3102850 TI - Characterization of antigen purified from type 3 strains of Pasteurella multocida and its use for an enzyme-linked immunosorbent assay. AB - Surface antigens were purified from a type 3, 4 rabbit isolate of Pasteurella multocida designated as R11146. Two protein peaks were obtained by gel filtration with Sephadex G-200 from crude saline extract. Major antigenic activity was detected in the first peak. The first peak was absorbed onto DEAE-cellulose and eluted by a linear gradient of NaCl. Four fractions eluted from the column contained a single antigen which was identical to an antigen purified from another type 3 strain, P-1059. Also, they uniformly contained two protein species of molecular weights of 44,000 and 25,500. Six Pasteurella-free rabbits were infected intranasally with R11146 isolate and antibody response was determined by an enzyme-linked immunosorbent assay (ELISA) with the use of an antigen purified from P-1059 strain. Serum samples from the infected rabbits showed ELISA titers at the plateau stage by 21 or 28 days post-inoculation. Highest titers ranged from 1:15,000 to 1:16,000, while all the preinoculation sera had titers lower than 1:10. The high titers generally persisted for longer than 98 days after the infection. These results indicate that ELISA using a purified type 3 antigen is useful to detect P. multocida infection in rabbits by a type 3-related strain. PMID- 3102851 TI - Serologic methods for detection of Pasteurella multocida infections in nasal culture negative rabbits. AB - An agar gel-diffusion test (AGDT) and an enzyme-linked immunosorbent assay (ELISA) were utilized to detect serum antibodies against Pasteurella multocida in naturally infected rabbits derived originally from a Pasteurella-free colony. The antigen used in both assays was purified from a serotype 3 (P-1059) strain of P. multocida. Among 47 serum samples tested 15 (32%) were seropositive; 12 (26%) of which were both AGDT and ELISA-positive, while 3 (6%) were ELISA-positive only. All rabbits examined were normal clinically and negative to repeated nasal cultures, but subsequent cultures at necropsy demonstrated the presence of P. multocida in 11 of the AGDT-positive rabbits and in 14 of the ELISA-positive rabbits. The organism was isolated most frequently from the naso-oropharynx and the tympanic bullae. Serotyping of isolates recovered from the nasopharynx were determined to be serotype 3 or 3,12. Ten seronegative rabbits also were necropsied and none were found harboring P. multocida. These preliminary data indicate that the application of an enzyme-linked immunosorbent assay may prove efficacious in identifying apparently healthy, consistently nasal culture negative rabbits as subclinical carriers of P. multocida. PMID- 3102852 TI - Encephalitis associated with Trypanosoma cruzi in a Celebes black macaque. AB - Progressive central nervous system depression developed in a Celebes black macaque (Macaca nigra) acquired from a zoo in Texas. A spinal tap revealed motile trypanosomes in the spinal fluid. Histological examination of the heart and brain revealed focal myocarditis and intracellular amastigotes, respectively. PMID- 3102853 TI - Decreased lung metastasis and tumor growth in parenterally fed mice. AB - The influence of alternate forms of nutritional support on primary tumor growth rate, tumor DNA synthesis rate, and number of lung metastases was examined in Swiss mice bearing subcutaneously implanted Lewis lung carcinoma (LLC). From Day 14 through 22 postimplant, mice were fed by continuous intravenous infusion of dextrose/amino acid (TPN), were offered the same solution from a feeding bottle (PO), were offered a casein-based, solid diet (CASEIN), or were infused with an electrolyte (ELECT) solution while energy and nitrogen were provided from the casein diet. Tumor weight and doubling time were decreased in the PO group compared to CASEIN; however, host weight decreased by 22% in the PO group. Tumor weight and DNA synthesis were decreased in the TPN group compared to CASEIN, and host weight increased by 4.6%. The decreased rate of tumor growth in the PO group was not reflected in a decrease in DNA synthesis, perhaps a result of the circadian pattern of DNA synthesis as previously reported for LLC. The number of metastatic lung nodules was significantly decreased in both the TPN and ELECT groups compared to PO and CASEIN, suggesting that intravenous fluid load rather than nutrient intake was the causative factor. In this host-tumor system, parenteral feeding was associated with a decrease in primary tumor weight and DNA synthesis rate, maintenance of host weight, and a decrease in pulmonary metastatic disease compared to mice fed a conventional diet. PMID- 3102854 TI - Use of serum CPK-MM to monitor response to nutritional intervention in catabolic surgical patients. AB - Nutritional status of surgical patients is widely assessed using anthropometrics, visceral proteins, and urinary nitrogen losses. Since assay of muscle-specific marker 3-methylhistidine (3MH) is currently limited to research laboratories, routine use of serum creatinine phosphokinase (CPK) and myoglobin is potentially useful in monitoring nutritional repletion of stressed patients. An acute and a temporal phase human studies were done to test this hypothesis. After an overnight fast, nondiabetic, noncardiac patients were given an IVGTT (0.5 g/kg) 3 days after a standard abdominal midline operation. Glucose, insulin, total CPK, myoglobin, and 3-methylhistidine were measured serially. Baseline CPK was elevated threefold above normal range of upper limits, whereas myoglobin was at the upper limit of normality. After the IVGTT insulin rose, (P less than 0.005) and CPK and 3MH fell (P less than 0.005) whereas myoglobin rose and remained elevated throughout the study (P less than 0.05). As long as insulin levels remained elevated, CPK remained depressed. With sufficient TPN to induce positive nitrogen balance (35 kcal and 0.2 g N/kg/day), elevated CPK levels fell and remained depressed in direct correlation with elevated insulin. Greater than 95% of total serum CPK consisted of the isoenzyme CPK-MM. These initial studies indicate that total serum CPK is useful in monitoring the short-term responses of postoperative catabolic patients who receive nutritional repletion. PMID- 3102855 TI - Beneficial effects of ibuprofen in oleic acid induced lung injury. AB - Metabolites of arachidonic acid, particularly thromboxanes, have been implicated as mediators of lung injury. The formation of thromboxane A2 can be decreased by glucocorticoid steroids by inhibiting the enzyme phospholipase A2 or by ibuprofen which inhibits fatty acid cyclooxygenase. This study was performed to determine if ibuprofen, methylprednisolone, or a combination of both could improve the pulmonary injury induced by oleic acid. Five groups of dogs were instrumented with pulmonary artery and extravascular lung water (EVLW) catheters and ventilated with 100% O2. Serial determinations of hemodynamic and pulmonary parameters were performed before and after oleic acid infusion. Plasma immunoreactive thromboxane B2 (iTxB2) and ibuprofen levels were also determined. Oleic acid rapidly induced a significant pulmonary injury as evidenced by hypoxemia and increases in extravascular lung water. Plasma iTxB2 rose significantly in the control group receiving only oleic acid. Pulmonary function and hemodynamic parameters were not changed by ibuprofen infusion alone. Ibuprofen attenuated the oleic acid induced hypoxemia and increased EVLW but did not significantly reduce plasma iTxB2. Methylprednisolone did not prevent the increase in plasma iTxB2 and was less effective than ibuprofen in preventing hypoxemia and increases in EVLW. The combination of ibuprofen and methylprednisolone did significantly inhibit the production of iTxB2, however in combination they protected less against the hypoxemia and increased EVLW than either agent alone. These results indicate that ibuprofen may have a protective effect in oleic acid induced lung injury that is not mediated through the inhibition of fatty acid cyclooxygenase. The results are also further evidence that thromboxane is probably not a pathogenetic factor in oleic acid induced lung injury. PMID- 3102857 TI - Interleukin-2 stimulus-response coupling is calcium independent. AB - This study investigated the role of calcium (Ca2+) as a second messenger in the stimulus-response coupling of interleukin 2 (IL 2) binding to its specific receptor that results in lymphocyte proliferation. Although the Ca2+ channel blockers verapamil, nifedipine, and diltiazem induced a dose-dependent inhibition of [3H]-thymidine incorporation by HT-2 cells in response to recombinant human and purified rat IL 2, the stimulation indices of the treated and untreated cells were equivalent. Stimulation of HT-2 cells with recombinant human IL 2 (rIL 2) did not result in an increase in the concentration of intracellular free Ca2+ [( Ca2+]i), using the fluorescent intracellular Ca2+ indicator Fura-2AM. Conversely, partially purified rat IL 2 did cause an increase in [Ca2+]i that was not inhibited by the channel blockers or by chelation of extracellular free Ca2+. Thus, contaminating components in the partially purified rat IL 2, and not the IL 2 itself, resulted in increased [Ca2+]i by mobilization from intracellular stores. These results demonstrate that inhibition of lymphocyte proliferation by verapamil, nifedipine, and diltiazem is not due to an uncoupling of the IL 2 lymphokinetic signal, and stimulation of HT-2 cells using rIL 2 does not increase [Ca2+]i, and thus does not employ Ca2+ as a second messenger. PMID- 3102856 TI - Effect of Cuscuta chinensis water extract on 7,12-dimethylbenz[a]anthracene induced skin papillomas and carcinomas in mice. AB - Cuscuta chinensis, known as Aftimun, is reputed to have antitumour activity in the Unani system of medicine in India. The effect of a hot water extract of C. chinensis on 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin papillomas and carcinomas in Swiss albino mice was studied. Oral administration of the extract (1 g/kg body wt) thrice a week in 22 mice, started on the tenth day after the first application of DMBA to the 252nd day, markedly delayed the appearance and retarded the growth of papillomas and the incidence of carcinoma, relative to a control group with 28 mice, in a two-stage system of tumorigenesis. Its prophylactic effect was found to be statistically significant. PMID- 3102858 TI - Infusion flow rates of whole blood and AS-1-preserved erythrocytes: a comparison. AB - We compared the flow rates of whole blood and erythrocytes resuspended in a new preservative solution (AS-1, consisting of adenine, dextrose, mannitol, and saline) which results in an erythrocyte preparation with a hematocrit lower than that of packed erythrocytes. When 100 ml of AS-1 solution is added to erythrocytes, a hematocrit of 59 +/- 5% is consistently obtained, and the resultant product has an improved flow rate. When we compared the infusion flow rates of whole blood and AS-1-preserved erythrocytes in vitro and in vivo, we found that flow times were shorter for AS-1 erythrocytes than for whole blood in vitro and in vivo, the flow rates of AS-1 erythrocytes and whole blood when expressed per volume were similar in vivo, and the flow rate of AS-1 erythrocytes for erythrocyte mass delivery in vivo was superior to that of whole blood. Thus, we conclude that the flow rates of the two products are comparable. PMID- 3102859 TI - Activities of daily living as quantitative indicators of nursing effort. AB - Functional assessments of elderly or disabled people requiring long-term care have been used by clinicians for many years, and functional assessment instruments are now being used as indicators of required nursing care and its cost. The authors examine the ability of functional assessment items and instruments to measure accurately the variation in nursing care used by nursing home patients, with analysis of 290 patients. Nursing times, measured for each patient by nurse category (registered and all other) and type of care (skilled and personal) measure resource consumption. Activities of daily living (ADLs): eating, bathing, dressing, toileting, transferring, and continence are used to measure functional abilities on a four-point scale: independent, supervised, assisted or helped, and dependent, as well as two derived scales: Katz's Index and Resource Utilization Groups. The four-point measurement scales for ADLs are found to be necessary as indicators of nursing time required by patients. As a consequence, the three-point scales used for ADLs in the Long-term Care Minimum Data Set are not adequate, at least in nursing homes, for resource allocation. The relationship of nursing times with individual ADLs is nonlinear, so linear statistical techniques such as principal components, canonical correlations, or linear regression are inappropriate to produce patient classification systems based on ADLs. Individual ADLs do not explain use of registered nursing care time as well as they do care time by other nursing staff. Therefore, resource allocation and staffing for registered nurses must be done separately from nursing personnel, using indicators other than ADLs. PMID- 3102860 TI - The Rand Health Insurance Study: a summary critique. PMID- 3102861 TI - The findings of the Rand Health Insurance experiment--a response to Welch et al. PMID- 3102862 TI - Short-term responses of hospitals to the DRG prospective pricing mechanism in New Jersey. AB - Short-term responses of hospitals to the New Jersey prospective payment system, which uses Diagnosis Related Groups (DRGs) to establish rates of compensation for all payers, were examined in this study. The sample consisted of 84 New Jersey hospitals that were subject to prospective payment and a comparison group of 76 hospitals. Hospitals comprising the comparison group located in eastern Pennsylvania, were reimbursed retrospectively. Regression equations, which included independent variables to control for market supply and demand conditions, were estimated for the cost per admission, cost per day, length of stay; and cases treated. The results indicate that increases in the cost per admission and cost per day were lower (P less than 0.05) in hospitals subject to the all payer DRG system than in those institutions that were reimbursed retrospectively. In addition, the results suggest that most of the cost savings attributed to the New Jersey DRG system are due to a reduction in the average length of stay. The paper concludes with policy implications. PMID- 3102863 TI - Length of stay in the VA. Long-term care in short-term hospitals. PMID- 3102864 TI - [Serogroup Y meningococcal meningitis in Spain: apropos of a case]. PMID- 3102865 TI - [Type B Neisseria meningitidis infection without meningitis]. PMID- 3102866 TI - [Continuous partial epilepsy as the initial manifestation of nonketotic hyperglycemic decompensation]. PMID- 3102867 TI - [Biclonal gammopathy of unknown significance: apropos of 3 cases]. PMID- 3102868 TI - [Buccal nitroglycerin as an alternative to sublingual administration in the treatment of angina pectoris attacks]. PMID- 3102869 TI - Hunter's syndrome: a study in airway obstruction. AB - Hunter's disease is a genetically transmitted defect known to produce mucopolysaccharide infiltration of multiple organ systems. Upper airway obstruction is caused by an enlarged tongue, deformed pharynx, and short, thick neck. Its eventual lethal outcome by the second decade of life is known to result from an infiltrative cardiomyopathy leading to irreversible heart failure. Instead, our recent experience in the care of five patients with this disorder suggests the lethal event is related to progressive obstruction sequentially involving the upper, mid, and lower airway characterized by gradual deformation and collapse of the trachea. Autopsy and histopathologic whole organ sections demonstrate anteroposterior flattening of the trachea and bronchi with submucosal thickening producing structural alterations known only to this disease. PMID- 3102870 TI - Effect of opioid peptides and potassium on the release of vasoactive intestinal polypeptide and thyrotropin releasing hormone from perifused rat hypothalami. AB - Opioid peptides have been demonstrated to stimulate prolactin secretion, and it has been postulated that this is mediated, at least in part, by an effect on hypothalamic prolactin releasing and release-inhibiting factors and neurotransmitters. The aim of this study was to investigate the effect of opioid peptides and depolarizing concentrations of K+ on the release of both vasoactive intestinal polypeptide (VIP) and thyrotropin releasing hormone (TRH) from perifused rat hypothalami. Both met-enkephalin and beta-endorphin stimulated the release of VIP significantly whilst not affecting the release of TRH. In addition, leu-enkephalin was found to have no effect on the release of either VIP or TRH. In contrast, depolarizing concentrations of K+ (50 mM) were found to cause the immediate release of TRH, but not VIP, from the same perifusion. The results suggest a role for VIP, but not TRH, in opioid peptide stimulated release of prolactin. In addition, the data indicates that a substance may be released in response to K+ depolarization which is inhibitory to the release of VIP. PMID- 3102871 TI - Ethanol induces rotational behavior in 6-hydroxydopamine lesioned mice. AB - Mice with unilateral striatal lesions created by 6-hydroxydopamine (6HDA) injection were screened for rotational (circling) behavior in response to injection of amphetamine and apomorphine. Those that rotated ipsilaterally in response to amphetamine and contralaterally in response to apomorphine were subsequently challenged with 1 to 3 g/kg (i.p.) ethanol. Surprisingly, ethanol induced dose related contralateral (apomorphine-like) rotation which, despite gross intoxication, was quite marked in most animals. No significant correlation was found between the number of turns made following ethanol and made after apomorphine or amphetamine. PMID- 3102872 TI - Keoxifene (LY 156758) inhibits follicle-stimulating hormone induced differentiation of cultured rat granulosa cells. AB - The direct effects of keoxifene (LY 156758), a benzothiphene-derived antiestrogen, on granulosa cell differentiation were examined in vitro using primary cultures of rat granulosa cells. The effect of keoxifene on FSH stimulated aromatase activity was biphasic in pattern, enhancing at lower concentrations (up to 10(-8) M), and inhibiting at higher concentrations (greater than 10(-6) M). Keoxifene inhibited FSH-stimulated progestin production in a dose dependent fashion with an IC50 of 5 X 10(-8) M. FSH-induced LH receptors were also inhibited by keoxifene with an IC50 of 5 X 10(-7) M. These findings suggest that keoxifene has direct pharmacologic actions at the ovarian level. In contrast to the earlier reported estrogenic actions of triphenylethylene antiestrogens at the ovarian level, the benzothiphene-derived antiestrogens may be clinically more useful in the management of estrogen-dependent malignancies. PMID- 3102873 TI - Stimulation of gonadotropin release by arachidonic acid and its lipoxygenase metabolites in superfused pituitary cells. AB - Luteinizing hormone and follicle stimulating hormone secretion was stimulated by 4 min pulses of arachidonic acid (3 X 10(-5) to 10(-4)M) in superfused rat pituitary cells. The effect of its lipoxygenase metabolites, 5-hydroxy-6,8,11,14 eicosatetranoic acid (5-HETE) and 15-hydroxy-5,8,10,14-eicosatetranoic acid (15 HETE) was more potent on hormone release when added in the same dose. Using 3 X 10(-5)M 5-HETE, its releasing activity on gonadotropins was comparable to that of GnRH (10(-9)M). 15-HETE (3 X 10(-5)M) was even more potent on LH and FSH secretion than 5-HETE. The secretory profile induced by 5-HETE and 15-HETE was also similar to that shown for GnRH, resulting in a rapid increase and a more prolonged decline of the hormone release. The addition of these fatty acids to superfused pituitary cells did not alter the response of the cells to their physiological ligand. These findings give further support to the proposal that metabolites of arachidonic acid may be involved in receptor-mediated mechanisms of gonadotropin release in pituitary cells. PMID- 3102874 TI - Isolation and purification of cellular retinol binding protein (CRBP) from goat mammary gland. AB - The cellular retinol binding protein (CRBP) from goat mammary gland has been isolated in pure form. The molecular weight of CRBP by gel filtration was 15,120 dalton. The 280/350 absorbance ratio of this protein was 1.20 and it gave a single precipitin line on immunodiffusion. The method is very simple and reproducible. PMID- 3102875 TI - Asymmetric distribution of arachidonic and n-3 polyunsaturated fatty acids in rat liver microsomal membranes under a fat-free diet. AB - Rats adapted to a corn oil or a fish oil diet were fed a fat-free diet, and changes in phospholipid polyunsaturated fatty acids (PUFA) in the inner and outer leaflets of liver microsomal membranes were followed for 18 wk. In rats previously adapted to a corn oil diet, arachidonic acid in phosphatidylcholine and phosphatidylethanolamine in the inner and outer leaflets did not decrease quickly; rather, linoleic acid decreased more than arachidonic acid for the first three weeks of feeding the fat-free diet. Even at 18 wk, 40-50% of the beginning arachidonic acid levels were still retained. In contrast, in rats previously adapted to a fish oil diet, the n-3 PUFA were quickly decreased by the fat-free diet to only 10-30% at 18 wk. Due to the appearance and increase of n-9 eicosatrienoic acid in the replacement of the n-3 and n-6 PUFA, total PUFA did not decrease in the inner and outer phosphatidylcholine in either group, but decreased somewhat in the phosphatidylethanolamine due to the insufficient increase of the n-9. On the other hand, the overall degrees of unsaturation in phosphatidylcholine fatty acids were always higher in the outer than in the inner leaflets and were not altered by feeding the fat-free diet even for 18 wk. Thus, the results appear to reveal the physiological importance of unsaturation ratio of fatty acids and the necessity of arachidonic acid in each membrane leaflet. PMID- 3102876 TI - [Arterial oxygen saturation around the period of tracheal intubation--an assessment of oxygenation time]. PMID- 3102877 TI - A computerized information system. PMID- 3102878 TI - Diabetes and the school nurse. PMID- 3102879 TI - Hyaluronidase for treating intravenous extravasations. PMID- 3102880 TI - Gavage tube insertion in the premature infant. PMID- 3102881 TI - Prostaglandin gel for cervical ripening. PMID- 3102882 TI - Adolescent suicide attempts by acetaminophen ingestion. PMID- 3102883 TI - Parenting roles: expectation versus reality. PMID- 3102884 TI - How parents of children with chronic conditions perceive their own needs. PMID- 3102885 TI - Sensory capabilities of the fetus. PMID- 3102886 TI - Munchausen syndrome by proxy. PMID- 3102887 TI - Covergowns for newborn infection control? PMID- 3102888 TI - Teaching patients to manage complex, long-term care. PMID- 3102889 TI - Contents of nurses' detailed notes. PMID- 3102890 TI - Interrater reliability: essential for research and practice. PMID- 3102891 TI - Allergic and pseudoallergic reactions to non-narcotic analgesics. AB - Pulmonary side effects are relatively rarely observed with analgesics and anti inflammatory drugs. However, some patients react to the ingestion of such drugs with bronchoconstriction and asthmatic attacks. In only a small percentage of these patients is a true allergic mechanism underlying the pulmonary reaction to the drugs. In most of the patients the basis for the pulmonary side effects is pseudoallergic. The molecular mechanism of pseudoallergy is not completely understood. However, several hypotheses have been put forward, such as drug induced stimulation of kinin receptors, activation of the complement system or interference with eicosanoid biosynthesis. The last hypothesis is attractive, since it could explain the similar sensitivity of such patients to drugs which are completely different chemically. It is not known, however, if the crucial drug effect on arachidonic acid metabolism is inhibition of synthesis of a bronchodilator eicosanoid such as prostaglandin E2 or increased synthesis of bronchoconstrictor eicosanoids such as leukotrienes. PMID- 3102892 TI - The role of prostaglandin synthesis inhibition in the renal syndromes associated with non-narcotic analgesics. AB - Prostaglandin (PG) synthesis in the kidney is localised to specific sites and is not uniformly present throughout the nephron. It is generally accepted that the regional heterogeneity of PGs, as well as the lack of vascular communications between the medulla and cortex, dictate that PGs [primarily prostacyclin (PGI2)] synthesised in the cortex (glomeruli and vasculature) regulate cortical function, while PGs (primarily PGE2) synthesised in the medulla (collecting tubule and medullary interstitial cells) regulate medullary function. Measurement of urinary unmetabolised PGs, or their stable hydration products, provides the best clinical assessment of the state of renal PG production. Under physiological circumstances, renal function is not critically dependent upon the integrity of PG synthesis, possibly because other regulatory mechanisms can compensate for PG synthesis inhibition. However, when renal PG synthesis is activated in response to altered haemodynamics (e.g. cirrhosis with ascites) or is pathologically reduced (e.g. chronic glomerular disease) then the consequences of pharmacological inhibition can become clinically apparent and measurable. In these circumstances, drugs that inhibit renal cyclo-oxygenase activity can acutely reduce glomerular filtration rate and renal blood flow by 30 to 50%. These functional changes are usually reversible upon discontinuing the drug. The long term consequences of renal PG synthesis inhibition are more difficult to assess. Theoretically, chronic inhibition of renal PG synthesis might be responsible for medullary ischaemia, possibly contributing to the picture of so called analgesic nephropathy. Selective sparing of renal cyclo-oxygenase activity can be obtained by at least 3 mechanisms: differential 'sensitivity' of the glomerular cyclo-oxygenase; selective intra-renal inactivation of an active metabolite of the drug; differential rate of recovery of glomerular cyclo oxygenase following irreversible acetylation by aspirin. The recent demonstration of a functional correlate of such biochemical selectivity suggests novel strategies for reducing the chronic renal toxicity of cyclo-oxygenase inhibitors. PMID- 3102893 TI - Multiple myeloma and severe renal failure: a clinicopathologic study of outcome and prognosis in 34 patients. AB - Renal failure (RF) occurring in the course of multiple myeloma is often judged irreversible and generally considered an ominous complication. The aim of the present study was to re-evaluate the outcome, triggering conditions and prognostic factors of severe RF in a series of 34 patients, 33 to 90 years old. RF was totally reversible in 7 patients and partially reversible in 9 although 6 of them had to be temporarily dialyzed. However, the improvement in renal function was often very slow as indicated by an average recovery time of 115 days. The high rate of RF reversibility was associated with markedly lengthened survival. Review of triggering events confirmed the leading role of dehydration and hypercalcemia, but further suggested that intake of nonsteroidal anti inflammatory drugs and renal infection might play a part in the development of RF. Systematic statistical analysis of potential prognostic factors showed that the outcome was significantly more severe in females, but age, myeloma characteristics including tumor mass, calcemia, and triggering events had no predictive value. The most reliable prognostic indicators were provided by analysis of kidney biopsy performed in 30 patients. Complete recovery from RF was observed only in the absence of global tubular atrophy and interstitial damage. In contrast, cast-induced tubular obstruction detected by the presence of Tamm Horsfall protein in urinary space of glomeruli did not seem to influence the outcome of RF. Finally, we analyzed the prognostic value of immunochemical properties of light chains (LC). Lambda LC were unexpectedly detected in 2 of 3 patients, as compared to a ratio of 1 to 3 in the population of normal and monoclonal Ig, but LC type did not correlate with the course of RF. Isoelectric points of LC measured in 32 patients were dispersed from 5.2 to 8.9 and bore only weak prognostic significance. These results underline the value of kidney biopsy and justify aggressive treatment including dialysis and chemotherapy. PMID- 3102894 TI - Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus. AB - Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) or proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc). A significant negative correlation was found between the presence of this C1q-binding material and subepithelial electron-dense deposits, suggesting that the presence of this material contributed to the absence of subepithelial immune deposits. Large-molecular-weight C1qSP-binding material was also present, mainly in sera from patients with proliferative lesions. Furthermore, highly positive correlations were found between immune deposits in interstitial blood vessels and peritubular areas, and the concentrations of C1qSP binding IgG and rapidly sedimenting IgG in density gradient analysis. Overall, these findings are consistent with the hypotheses that circulating immune complexes contribute to the pathogenesis of glomerulonephritis and interstitial nephritis in patients with SLE, and that 6.6S C1q-binding IgG plays a role in the proliferative lesions of lupus glomerulonephritis. PMID- 3102895 TI - Increase in plasma high-density lipoprotein concentration following complete androgen blockage in men with prostatic carcinoma. AB - There is evidence that endogenous estrogens have a positive effect on plasma high density lipoprotein (HDL) concentration, whereas the relation between HDL and male sex hormones is unclear, since both positive and negative effects have been reported. This study examined the effects of LHRH agonist in combination with an antiandrogen on plasma lipids and lipoproteins in 17 elderly men with prostatic carcinoma. Subjects were examined prior to and after therapy at 4-week intervals up to 16 weeks. Prior to therapy, their lipid and lipoprotein profiles were not significantly different from a control group composed of individuals of similar age and living in the same community area. Following therapy plasma levels of testosterone and dihydrotestosterone were markedly decreased (above 90%) and their residual activity neutralized through effective use of an antiandrogen. Plasma estradiol decreased between 65% and 85% and the concentration of cortisol was unaffected. The very low density lipoprotein (VLDL) apo-B decreased and low density lipoprotein (LDL) apo-B increased; thus, no change was observed in the total plasma apo-B levels. Total plasma cholesterol increased by 6% (baseline v peak values, mg/dL, mean +/- SEM; 219 +/- 9 v 233 +/- 9, P less than 0.05) due to a significant rise in HDL cholesterol concentration (45.5 +/- 2.8 v 56.5 +/- 3.6, P less than 0.01). Both VLDL and LDL cholesterol levels remained unchanged. The mean elevation of 21% in HDL cholesterol was accompanied by a significant rise in HDL apo-A concentration (161 +/- 6 v 193 +/- 10, P less than 0.01), thus suggesting an increase in HDL mass and/or particle number.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102896 TI - Insulin insensitivity and skeletal muscle enzyme activities in response to overinsulinization in the rat. AB - Periods of overinsulinization with low blood glucose levels are a recognized feature of intensive insulin injection therapy. The relationship of these features to insulin insensitivity is controversial, and the mechanisms underlying any such changes are unclear. Normal rats have therefore been overinsulinized for 6 weeks before measurement of in vivo insulin sensitivity by the glucose clamp technique. Skeletal muscle glycogen synthase and pyruvate dehydrogenase activities were measured at the end of the clamp. Sensitivity to insulin as measured by the glucose clamp technique at euglycemic levels was decreased in the insulin overtreated animals (glucose requirements, 108 +/- 2 mumol/min/kg v 170 +/- 10 mumol/min/kg, P less than 0.001). Total skeletal muscle glycogen synthase activity was increased in the experimental group (2.83 +/- 0.12 v 1.96 +/- 0.14 U/g wet weight, P less than 0.001), and as a result the active fraction was higher at the end of the clamp (0.79 +/- 0.04 v 0.66 +/- 0.04 U/g wet weight, P less than 0.05). Skeletal muscle glycogen content was consistent with the glycogen synthase activity. Pyruvate dehydrogenase in the same tissue showed increased activation prior to the clamp (6.6 +/- 0.6 v 4.7 +/- 0.6%, P less than 0.05), but neither active nor total activity was abnormal at the end of the clamp.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102897 TI - Methods for distinguishing ingested from adhering particles. PMID- 3102898 TI - Parasiticidal activity of macrophages against schistosomes. PMID- 3102899 TI - Stable 1,2-dioxetanes as labels for thermochemiluminescent immunoassay. PMID- 3102900 TI - Purification of tau protein from brain. PMID- 3102901 TI - Preparation, assay, and microinjection of fluorescently labeled cytoskeletal proteins: actin, alpha-actinin, and vinculin. PMID- 3102902 TI - Gel overlay methods for detecting specific protein-protein interactions. PMID- 3102903 TI - Purification and assay of vinculin, metavinculin, and talin. PMID- 3102904 TI - [Changes in the electrical characteristics of bacterial cells in the disruption of the barrier function of the cytoplasmic membrane]. AB - A change in the electro-orientation spectrum followed by a change in the electric characteristics of bacterial cells had been measured when the barrier function of the cytoplasmic membrane was disordered under the action of damaging physical and chemical factors. Analysis of changes in the spectra at a frequency of 10(4) to 10(7) Hz allows one to estimate the degree of cell damage in quantitative terms. The paper presents the results of comparing three procedures for such an estimation: inoculation onto solid growth media; linear regression analysis of an electro-orientation spectrum; comparison of the electro-orientation effect at a high frequency (ca. 5 X 10(5) Hz) and at a medium frequency (ca. 10(4) Hz). PMID- 3102905 TI - [Balance of macroergic compounds during the growth of Thiobacillus ferrooxidans]. AB - The balance of energy-rich compounds (ERC) was drawn up for the growth of Thiobacillus ferrooxidans in a medium with ferrous ions as an energy source. The balance items and the phosphorylating efficiency of oxidation (P/2e-) were calculated basing on the experimental yield values using the ERC balance equation. At a specific growth rate of 0.1 h-1, 55% of ferrous ions are used for the synthesis of cell biomass, 7.5% for maintainance, 4% of the ions are oxidized to reduce NAD+, and 34% are used to produce ERC necessary for the reduction. Here, 24% of ERC are used for the synthesis of monomers from CO2, 42% for the production of NADH, 24% for the biomass synthesis from monomers, and 10% for maintaining cell activity. The P/2e- for the oxidation of ferrous ions is 0.19 mole of ERC per 2e-. This is possible only when the [Fe3+]/[Fe2+] ratio in the cell periplasm is 1 X 10(3)-1 X 10(4). PMID- 3102906 TI - [Immunological characteristics of Methylomonas methanica membranes]. AB - Immune sera were prepared against the antigenic complexes in the fractions of Methylomonas methanica cell wall, cytoplasmic membrane and intracytoplasmic membranes. The membrane fractions were studied immunologically in the reactions of agglutination, immunofluorescence and immunodiffusion. Some common features as well as differences were found among the membrane fractions in the antigenic structure. The membranes of M. methanica were shown to contain species-, genera- and type-specific antigens. PMID- 3102907 TI - [Intracellular development of Bdellovibrio bacteriovorus]. AB - The intracellular growth of Bdellovibrio bacteriovorus, a bacterial parasite, was studied by a light-optical method using time-lapse cinemicrography. The organism was found to be capable of growth in the periplasmic space of filamentous cells of the host bacterium Pseudomonas fluorescens without any contact with the cytoplasmic membrane. Several B. bacteriovorus cells could grow simultaneously in the bdelloplasm. PMID- 3102908 TI - [New species of bacteria in the genus Kurthia--Kurthia sibirica sp. nov]. AB - Six aerobic gram-positive nonspore-forming bacterial strains belonging to the Kurthia genus were isolated from the Magadan (Susuman) mammoth found in the permafrost of the East Siberia. The strains are a phenotypically homogeneous group different from the two known species (K. zopfii and K. gibsonii) in requiring more vitamins, the absence of growth in a medium with 7% NaCl, and a low level of DNA-DNA hybridization (not more than 45%). Moreover, the strains differ from K. zopfii in the synthesis of a yellow pigment, the activity of phosphatase, and the absence of coccoid forms; the bacteria differ from K. gibsonii in the absence of growth at a temperature above 40 degrees C. The organisms are referred to as Kurthia sibirica sp. nov. The type strain 13-2 has been deposited in the All-Union Collection of Microorganisms as strain VKB B 1549. PMID- 3102909 TI - [Coagulation of bacteria by the action of montmorrillonite]. AB - Conditions were studied for the coagulation of aggregation-stable Bacillus subtilis, Flavobacterium rigens and Escherichia coli cell dispersions. Their aggregative stability decreased when montmorillonite, a clay mineral, was added to a weakly acid medium or in the presence of Al3+ ions. Bacterial heterocoagulation under the action of montmorillonite can be used as a universal strategy for biomass isolation from aqueous dispersion media. PMID- 3102910 TI - [A method for determining the CO2 released by resting cells of microorganisms during the oxidation of hydrocarbons]. AB - A method is proposed for determining the oxidation of hydrocarbon substrates by microorganisms. The method is based on measuring the evolution of CO2 into the medium when the substrate is oxidized by washed microbial cells adsorbed on a spongy surface and incubated in a closed space into which CO2-free air is passed. PMID- 3102911 TI - [Esterase activity of hydrocarbon-oxidizing bacteria]. AB - The activity of esterase was studied in bacteria oxidizing hydrocarbons and belonging to the genera Rhodococcus, Arthrobacter and Pseudomonas. Indophenyl acetate was used as a substrate of the reaction catalysed by the enzyme. Exocellular esterases were not found. Endocellular esterases differed in their activity and thermostability both among the genera and among species of one and the same genus. PMID- 3102912 TI - [Final stages of the preliminary metabolism of 2,4,6-trinitrotoluene in Pseudomonas fluorescens]. AB - The work was aimed at studying the transformation of 2,4-diamino-6-nitrotoluene (2,4-DA), an intermediate product in 2,4,6-trinitrotoluene catabolism by microorganisms. The results allow one to propose the following scheme for the terminal steps of TNT preparatory metabolism: 2,4-DA----[phloroglucinol carboxylic acid]----phloroglucinol----pyrogallol----ring cleavage. PMID- 3102913 TI - Nordic (cross-country) skiing injuries in Australia. AB - A retrospective study of 88 nordic skiing injuries from the 1984 and 1985 skiing seasons in Australia is presented. To our knowledge, this is the largest study to date of such injuries. These injuries are compared with alpine skiing injuries from the same medical clinic for the 1985 skiing season. There was a much lower incidence of injury from nordic skiing; however, when injuries did occur, they tended to be more serious than those of alpine skiing and frequently required immediate evacuation to hospital for treatment. As the nordic skier is relatively isolated from medical services, these findings need to be considered in the future planning of rescue services for such skiers. PMID- 3102915 TI - [Intensive care medicine 1986]. PMID- 3102914 TI - Single-dose antibiotic therapy for the treatment of uncomplicated anogenital gonorrhoea. AB - Appropriate single-dose therapy will cure in excess of 95% of cases of uncomplicated anogenital gonorrhoea. Changes in the susceptibility of local isolates of Neisseria gonorrhoeae, particularly the emergence of beta-lactamase producing (and therefore penicillin-resistant) strains, have necessitated the modification of standard treatment regimens. Different patterns of antibiotic resistance have been documented in different regions of Australia and therapeutic regimens that are appropriate for use in different regions are recommended. PMID- 3102916 TI - The economic costs of the health effects of smoking, 1984. AB - The impact of cigarette smoking on morbidity and mortality in the United States is well known. Economic consequences of these health effects--expenditures for medical care and the value of productive output lost--have been estimated in many ways. This original prevalence-based analysis of attributable risks indicates a staggering $54 billion cost to the nation. Concern over such misallocation of resources to harmful uses is demonstrably justified. PMID- 3102917 TI - Human immunodeficiency virus infection in transfusion recipients and their family members. PMID- 3102918 TI - Smokeless tobacco use in rural Alaska. PMID- 3102919 TI - Advancements in meeting the 1990 hypertension objectives. PMID- 3102920 TI - Mumps--United States, 1985-1986. PMID- 3102921 TI - Antibody to human immunodeficiency virus in female prostitutes. PMID- 3102922 TI - Disseminated gonorrhea caused by penicillinase-producing Neisseria gonorrhoeae- Wisconsin, Pennsylvania. PMID- 3102923 TI - Pertussis surveillance--United States, 1984 and 1985. PMID- 3102924 TI - Progress toward achieving the national 1990 objectives for sexually transmitted diseases. PMID- 3102925 TI - Survey of worksite smoking policies--New York City. PMID- 3102926 TI - Years of potential life lost before age 65 due to perinatal conditions--United States, 1980-1983. PMID- 3102927 TI - Self-reported changes in sexual behaviors among homosexual and bisexual men from the San Francisco City Clinic cohort. PMID- 3102928 TI - Symptoms of irritation associated with exposure to glutaraldehyde--Colorado. PMID- 3102929 TI - Outbreak of occupational hepatitis--Connecticut. PMID- 3102930 TI - Restaurant-associated botulism from mushrooms bottled in-house--Vancouver, British Columbia, Canada. PMID- 3102931 TI - Guidelines for diabetic eye disease control--Kentucky. PMID- 3102932 TI - An imported case of rabies in an immunized dog. PMID- 3102933 TI - Demonstration to improve care practices for diabetic patients in primary care centers--Florida. PMID- 3102934 TI - Penicillinase-producing Neisseria gonorrhoeae--United States, 1986. PMID- 3102935 TI - Acute rheumatic fever--Utah. PMID- 3102936 TI - Prevention policy review group. Summary of meeting--March 27, 1986. PMID- 3102937 TI - Survey of non-U.S. hemophilia treatment centers for HIV seroconversions following therapy with heat-treated factor concentrates. PMID- 3102938 TI - Unintentional ingestions of prescription drugs in children under five years old. PMID- 3102939 TI - Outbreak of hepatitis B associated with an oral surgeon--New Hampshire. PMID- 3102940 TI - Tuberculosis and AIDS--Connecticut. PMID- 3102941 TI - [Effect of proteolytic enzymes and bile salts combined with EDTA 4Na on the dissolution of calcium bilirubinate gallstones]. AB - In vitro dissolution of the gallstones was studied in order to evaluate the effect of proteolytic enzyme (Pronase E) and bile acids (CA, CDCA, UDCA and TCA) on the dissolution of the calcium bilirubinate gallstones with ethylene diamine tetraacetic acid (EDTA 4Na) solution. In this study, the slices and the whole concrement of the calcium bilirubinate gallstones were dissolved with an admixture of the chemical agents. It was shown that a pretreatment with 0.5-1.0% solution of Pronase E made the slices susceptible to the dissolution with EDTA 4Na (1.0%). Although, the addition of Pronase E to an admixture of CA and EDTA 4Na did not increase the efficacy of the slices dissolution, it seemed to be effective in the dissolution of the whole concrement. Regarding to the effect of the bile acids on the slices dissolution, each bile acid was not significantly different from the others when it was used as a 25mM admixture with EDTA 4Na. One hundred milimoles solution of TCA had 2-fold activity of a 25mM solution in the dissolution of both the slices and the whole concrement when it was used in combination with EDTA 4Na. The results suggest that a pretreatment of the calcium bilirubinate gallstones with Pronase E is of great advantage in dissolution therapy. It is also suggested that TCA (100mM in EDTA 4Na), which can be applied in human beings without any serious side effect, is helpful in the treatment of calcium bilirubinate gallstones in clinical cases. PMID- 3102942 TI - Cell surface galactosyltransferase as a recognition molecule during development. AB - Recent results from our laboratory suggest that a variety of cellular interactions during development are mediated, in part, by the binding of a cell surface enzyme, galactosyltransferase (GalTase), to its specific lactosaminoglycan (LAG) substrate on adjacent cell surfaces and in the extracellular matrix. Our present interest in surface GalTase developed from earlier biochemical studies of a series of morphogenetic mutations in the mouse which map to the T/t-complex. These studies identified a specific defect in the regulation of surface GalTase activity on morphogenetically abnormal cells, while eight other enzymes showed normal activity. This led us to consider the unique function of surface GalTase in those cell interactions that are influenced by mutations of the T/t-complex. By using a multidisciplinary approach, which included genetic, biochemical and immunological probes, we have found that GalTase functions as a surface receptor during fertilization, early embryonic cell adhesions, and embryonic cell migration on basal lamina matrices. Recently, we have examined the expression of surface GalTase during spermatogenesis, as well as the fate of sperm GalTase following the acrosome reaction. This paper summarizes the results of these studies, as well as others, which suggest that GalTase functions as a surface receptor during those cell interactions regulated by the T/t-complex alleles. PMID- 3102943 TI - Differential processing of Asn-linked oligosaccharides on pituitary glycoprotein hormones: implications for biologic function. AB - Luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone from pituitary and chorionic gonadotropin from placenta are a family of glycoproteins, each consisting of an alpha and beta subunit. Within an animal species, the alpha subunit of all four hormones contains the identical amino acid sequence, while each beta subunit is distinct and confers biologic specificity to the hormone dimer. Despite sharing common alpha subunits, these hormones bear Asn linked oligosaccharides which differ in structure. Whereas chorionic gonadotropin contains exclusively neutral and sialylated oligosaccharides, the pituitary hormones bear neutral, sialylated, sulfated, and sialylated/sulfated structures. The sulfated oligosaccharides are unique in structure and are more prevalent on certain pituitary hormones, indicating that the synthesis of these unusual oligosaccharides is tightly regulated. The differences in oligosaccharide structures in conjunction with the highly specific endocrine responses elicited by these hormones, suggest an important functional role for the oligosaccharides, such as metabolic clearance, control of hormone response, modulation of hormone potency, and/or intracellular sorting of hormones into separate secretory granules. PMID- 3102945 TI - GAL4 of Saccharomyces cerevisiae activates the lactose-galactose regulon of Kluyveromyces lactis and creates a new phenotype: glucose repression of the regulon. AB - A Kluyveromyces lactis mutant defective in lac9 cannot induce beta-galactosidase or galactokinase activity and is unable to grow on lactose or galactose. When this strain was transformed with the GAL4 positive regulatory gene of Saccharomyces cerevisiae it was able to grow on lactose or galactose as the sole carbon source. Transformants bearing GAL4 exhibited a 4.5-h generation time on galactose or lactose, versus 24 h for the nontransformed lac9 strain. A K. lactis lac9 strain bearing two integrated copies of GAL4 showed 3.5-fold induction of beta-galactosidase activity and 1.8-fold induction of galactokinase activity compared with 15.6-fold and 4.4-fold induction, respectively, for the LAC9 wild type strain. In transformants bearing 10 integrated copies of GAL4, the induced level of beta-galactosidase was nearly as high as in the LAC9 wild-type strain. In addition to restoring lactose and galactose gene expression, GAL4 in K. lactis lac9 mutant cells conferred a new phenotype, severe glucose repression of lactose and galactose-inducible enzymes. Glucose repressed beta-galactosidase activity 35 to 74-fold and galactokinase activity 14- to 31-fold in GAL4 transformants, compared with the 2-fold glucose repression exhibited in the LAC9 wild-type strain. The S. cerevisiae MEL1 gene was repressed fourfold by glucose in LAC9 cells. In contrast, the MEL1 gene in a GAL4 lac9 strain was repressed 20-fold by glucose. These results indicate that the GAL4 and LAC9 proteins activate transcription in a similar manner. However, either the LAC9 or GAL4 gene or a product of these genes responds differently to glucose in K. lactis. PMID- 3102944 TI - Induction of urokinase-type plasminogen activator by UV light in human fetal fibroblasts is mediated through a UV-induced secreted protein. AB - Plasminogen activator was previously shown to be induced by UV light in human cells with low capacity to repair UV-induced DNA lesions. We now show that in human fetal fibroblasts UV light enhanced the two mRNA species coding for the urokinase-type plasminogen activator (uPA) and the tissue-type plasminogen activator, but immunological analysis revealed exclusively uPA activity. Several independent and complementary experiments indicated that induction of uPA was mediated, apparently entirely, through a UV-induced, secreted protein (UVIS) in the growth medium of irradiated cells. First, elevation of uPA mRNA after irradiation was severely blocked by cycloheximide. Second, replacement of conditioned medium in irradiated cells while the rate of plasminogen activator induction was maximal rapidly and completely stopped any further increase in uPA activity. Third, addition of the same removed conditioned medium to nonirradiated cells mimicked UV light in enhancing the level of uPA activity as well as that of uPA mRNA. Fourth, UVIS activity was completely lost by treating the conditioned medium with trypsin but not with nucleases. Kinetic measurements indicated that the accumulation of UVIS rather than the induction of uPA by UVIS conferred the rate-limiting step in the overall process of uPA induction. Both UV light and UVIS acted synergistically with inhibitors of DNA repair for uPA induction. Based on these results, a model is proposed implicating relaxation of DNA torsional stress of an as yet undefined DNA sequence(s) in the induction of UVIS, which is then responsible for activation of the uPA gene. PMID- 3102946 TI - Expression of H-ras correlates with metastatic potential: evidence for direct regulation of the metastatic phenotype in 10T1/2 and NIH 3T3 cells. AB - Using three independent approaches, we studied the effects of H-ras on metastasis formation. Analysis of five in vitro-ras-transfected 10T1/2 clones with either flat or refractile morphologies revealed a relationship between metastatic potential, H-ras expression, and anchorage-independent growth. Four metastatic variants derived from a poorly metastatic, low-H-ras-expressing line all expressed high levels of H-ras RNA and grew efficiently in soft agar. Activation of H-ras expression in the metastatic tumors had occurred through amplification and rearrangement of H-ras sequences. In addition, preinduction of p21 synthesis in NIH 3T3 line 433, which contains v-H-ras under transcriptional control of the glucocorticoid-sensitive mouse mammary tumor virus long terminal repeat, significantly increased metastatic efficiency. Glucocorticoid treatment of normal or pEJ-transformed NIH 3T3 cells did not affect metastatic potential. These data reveal a direct relationship between ras expression and metastasis formation and suggest that metastatic and transformed phenotypes may be coregulated in ras transformed 10T1/2 and NIH 3T3 cells. PMID- 3102947 TI - Human purine nucleoside phosphorylase and adenosine deaminase: gene transfer into cultured cells and murine hematopoietic stem cells by using recombinant amphotropic retroviruses. AB - Cell lines were established which produced high titers (approximately 10(6) infectious units per ml) of amphotropic, replication-defective recombinant retroviruses which transduced sequences encoding either human purine nucleoside phosphorylase (PNP) or adenosine deaminase (ADA). These viruses also contained a human hypoxanthine phosphoribosyltransferase gene as a selectable marker and a mouse metallothionein promoter (MMP) sequence just upstream from the PNP or ADA genes. Virus structure was maintained through the replication cycle if a short (216-base pair) MMP sequence was used. However, the use of a longer (1,834-base pair) MMP sequence resulted in the deletion of a significant portion of the recombinant virus genome, including the transcriptional regulatory elements of the MMP sequence. Northern analysis indicated a predominance of genome length transcripts in cells infected with deleted virus. The demonstration of substantial human PNP or ADA activity in virus-infected mouse fibroblasts by isozyme analysis suggested that active gene product was translated from either spliced or bicistronic message. The deleted ADA and PNP viruses were introduced into mouse hematopoietic stem cells by cocultivating freshly explanted bone marrow with virus producer cells. The infected marrow cells were injected into irradiated, syngeneic recipient mice, and the presence of integrated ADA or PNP proviral sequences was demonstrated in the DNA of spleen colonies by Southern analysis. Failure of these integrated proviral sequences to express active, human isozyme in spleen colony tissue indicated the existence of some regulatory constraint not active in cultured mouse cells. PMID- 3102949 TI - Functionally relevant membrane proteins of human and guinea-pig T lymphocytes. PMID- 3102948 TI - Extinction of expression of immunoglobulin genes in myeloma X fibroblast somatic cell hybrids. AB - Adherent hybrids between immunoglobulin-producing mouse myeloma cells and fibroblasts do not produce immunoglobulin polypeptide chains. These hybrids retained the actively rearranged immunoglobulin genes of the myeloma parental cells but lacked immunoglobulin heavy- and light-chain RNA transcripts. We conclude that the shutoff of immunoglobulin production in these hybrids occurs at the transcription or early processing level. PMID- 3102950 TI - Regulation of interleukin-2 receptor expression and receptor release. AB - The generation and cell surface expression of IL-2 receptors was monitored by: (i) an ELISA that permits quantitative determination of detergent-solubilized or soluble IL-2 receptors; and (ii) detection of the binding of 125I-labelled recombinant IL-2 and of anti-IL-2 receptor antibodies to receptor bearing cells. Upon lectin stimulation both high and low affinity IL-2 receptors became expressed in parallel at the cell surface. Both high and low affinity receptors were upregulated by IL-2. Upon lectin activation the amount of cell-associated receptors increased and on day 2 of the culture period IL-2 receptors were detectable in the culture supernatant. IL-2 upregulated both high and low affinity IL-2R expression on T-lymphoblasts. IL-2R bearing leukemic cells and T lymphoblasts released IL-2R when cultured in vitro. IL-2R release by T lymphoblasts was enhanced dramatically by IL-2. On the other hand, IL-2-receptor positive leukemic cells released receptors in an IL-2 independent manner. Release of receptors could also be detected in serum-free medium. At least a part of the released receptors could be specifically bound to immobilized pure recombinant IL 2 and to monoclonal anti-IL-2-receptor antibodies. Small but significant amounts of soluble IL-2 receptors were detectable in the sera of normal mice. In sera of mice inoculated with IL-2-receptor positive syngeneic leukemic cells, elevated levels of IL-2 receptors were detectable. Release of IL-2 receptors seems to represent one of the major routes by which the receptors are cleared from the cell surface. PMID- 3102951 TI - Rearrangements of T-cell receptor beta-chain genes in human leukaemias. AB - Rearrangements of the T-cell receptor (TCR), beta-chain genes and immunoglobulin (Ig) heavy chain genes in several T-cell leukaemias (T-ALL and ATL), and some B cell and myelogenous leukaemias were investigated. Two out of 15 cases of T-cell leukaemia tested failed to show a rearrangement pattern of TCR beta genes although both expressed mRNA for this gene. The remaining 13 cases showed diverse patterns of rearrangements involving either C beta 1, C beta 2 or both. C beta 1 but not C beta 2 was deleted in some of the T-cell leukaemias. Polyclonal T cells from four normal individuals showed the germ line pattern and an additional two bands in Hind III digested DNA. Except for one, all cases of C-ALL (B-cell leukaemia) showed a rearranged JH locus which was not evident in any of T-cell leukaemias studied. One case of B-cell leukaemia showed a rearrangement of both TCR beta genes and JH genes. The results of these studies suggest that rearrangement of TCR and Ig genes occurs at a very early stage of differentiation of stem cells and does not appear to play a direct role in leukaemogenesis per se. PMID- 3102952 TI - [Acute and long-term effects of captopril in resistance-induced pulmonary hypertension in childhood and adolescence]. AB - 7 children and adolescents with pulmonary hypertension were examined with regard to the effect of Captopril as well on the pressure in the pulmonary artery and in the right ventricle as on the resistance in the systemic and pulmonary circulation and on the cardiac output. After initial application of Captopril 0.2 mg/kg body weight distinct oscillations of the data were measured, but with the exception of a small decrease of the mean pulmonary artery pressure (-8.5%) no determinable change was noticed. A decrease of the pulmonary artery resistance ( 17%), the mean pulmonary artery pressure (-10%) and the right ventricular pressure (-3%) was found under continuous application of Captopril 0.3 mg/kg body weight daily for a period of 7 months. The cardiac output increased (+16%) and the systemic resistance decreased (-16%). The changes of data were not statistically significant. Captopril did not have a reliable therapeutic effect on the pressure and resistance in the pulmonary circulation in children and adolescents with pulmonary hypertension. PMID- 3102953 TI - [DNA-methylases from different strains of Bacillus subtilis and Bacillus natto]. AB - DNA-methyltransferase activity has been detected in some of Bacillus subtilis and Bacillus natto strains. Two strains of Bacillus subtilis exhibited DNA-cytosine methyltransferase activity, and the strains of Bacillus natto exhibited DNA adenine methyltransferase activity. A possible effect of DNA-methyltransferase specificity on transformation efficiency is discussed. PMID- 3102954 TI - Cell and species differences in metabolic activation of chemical carcinogens. AB - Metabolic activation and DNA binding of aflatoxin B1 (AFB1), N nitrosodimethylamine (DMN) and benzo[a]pyrene (B[a]P) were compared in human, rat and mouse hepatocytes and human pulmonary alveolar macrophages (PAM). The degree of carcinogen activation by hepatocytes and PAM was measured by cell-mediated mutagenesis assays in which co-cultivated Chinese hamster V79 cells were used to monitor mutagenic metabolites. Hepatocytes from human, mouse and rat metabolized DMN and released the active metabolites to induce either ouabain- or 6 thioguanine-resistant mutation. The mutation frequencies mediated by hepatocytes of the 3 animal species were approximately 3-9 mutants/10(5) survivors at a concentration of 0.2 mM DMN. The variations of radioactivity bound to liver cell DNA were relatively small in cultured mouse, rat, and human hepatocytes exposed to 14C label DMN (0.5 mM) and the binding values were in a range of 6-12 X 10(3) pmoles/mg DNA. However, rat hepatocytes were at least 10-fold more effective than either human or mouse hepatocytes in generating mutagenic metabolites of AFB1 and also had a much higher AFB1 metabolite DNA-binding value. The AFB1 DNA-binding levels were 4.1, 12-27 (range), 120 pmoles/mg DNA respectively in mouse, human, and rat liver cells following AFB1 (3.3 microM) exposure for 20 h. Hepatocytes from the 3 animal species were unable to mediate mutation in the presence of 4 microM B[a]P; PAM activated B[a]P and effectively mediated mutation in the co cultivated V79 cells. In contrast to results with hepatocytes, PAM failed to generate enough mutagenic metabolites of AFB1 (3.3 microM) and the mediation of mutations was seen only at very high concentration of DMN (80 mM). The genotoxic effects of the 3 carcinogens on hepatocytes from different species in vitro were in agreement with the in vivo animal experiments in that mice are relatively resistant to AFB1 carcinogenesis whereas rats are sensitive; B[a]P is not effective as a complete liver carcinogen in adult rat and mouse whereas DMN induces liver cancer. PMID- 3102955 TI - Cytological characterization of Chinese hamster ovary X-ray-sensitive mutant cells, xrs 5 and xrs 6. II. Induction of sister-chromatid exchanges and chromosomal aberrations by X-rays and UV-irradiation and their modulation by inhibitors of poly(ADP-ribose) synthetase and alpha-polymerase. AB - The cell killing and induction of sister-chromatid exchanges (SCEs) by X-rays and short-wave ultraviolet (UV) irradiation in combination with inhibitors of DNA repair, 3-aminobenzamide (3AB), cytosine arabinoside (ara-C) or aphidicolin (APC) were studied in wild-type CHO-K1 and two X-ray-sensitive mutants, xrs 5 and xrs 6 cells. The spontaneous frequency of SCEs was similar in the mutants and the wild type CHO-K1 cells (8.4-10.3 SCEs/cell). Though X-rays are known to be poor inducers of SCEs, a dose-dependent increase in the frequency of SCEs in xrs 6 cells (doubling at 150 rad) was found in comparison to a small increase in xrs 5 and no increase in wild-type CHO-K1 cells. 3AB, an inhibitor of poly(ADP-ribose) synthetase increased the spontaneous frequency of SCEs in all the cell types. 3AB did not potentiate the X-ray-induced frequency of SCEs in any of the cell lines. Ara-C, an inhibitor of DNA polymerase alpha, increased the frequency of SCEs in all the cell lines. In combined treatment with X-rays, ara-C had no synergistic effect in xrs 5 and xrs 6 cells, but the frequency of SCEs increased in X irradiated wild-type CHO-K1 cells post-treated with ara-C. For the induced frequency of SCEs, CHO-K1 cells treated with X-rays plus ara-C behaved like xrs 6 cells treated with X-rays alone, suggesting a possible defect in DNA base damage repair in xrs 6 cells, in addition to the known defective repair of DNA double strand breaks (DSBs). Survival experiments revealed higher sensitivity of xrs 5 and xrs 6 mutant cells to the cell killing effect of X-rays in S-phase when compared to wild-type CHO-K1 cells. The mutants responded with lesser sensitivity to cell killing effect of ara-C and APC than CHO-K1 cells, the relative sensitivity to ara-C or APC being CHO-K1 greater than xrs 5 greater than xrs 6 cells. When X-irradiation was coupled with ara-C, the results obtained for survival were similar to those of the SCE test, i.e., unlike wild-type CHO-K1, no synergistic effect was observed in xrs 5 or xrs 6 cells. After UV-irradiation, the frequency of SCEs increased similarly in wild-type CHO-K1 and xrs 6 cells, but xrs 5 cells responded with lower frequency of SCEs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3102956 TI - Isolation and characterization of second chromosome mutagen-sensitive mutations in Drosophila melanogaster. AB - We have undertaken the study of a collection of 32 Drosophila melanogaster mus strains selected on the basis of developmental sensitivity to the DNA-damaging agents, methyl methanesulfonate (MMS), N-acetyl-2-aminofluorene (AAF), nitrogen mustard (HN2), and gamma-radiation. In total, 18 of these strains are sensitive to MMS. In turn, 14 of these exhibit unconditional MMS sensitivity (one of the latter mutants is lethal at 29 degrees C), whereas the other 4 are sensitive to MMS only at higher temperatures. Detailed analysis of the 7 strongest MMS sensitive strains reveals that they identify 4 new second chromosome mus loci. Two mus loci are each represented by two alleles. One mutant (mus205B1) is allelic to a previously characterized mus locus. Different MMS-sensitive mutants display patterns of mutagen cross-sensitivity (to AAF, HN2, benzo[a]pyrene (BP), and gamma-rays) that parallel the range of responses seen in previously recovered X-linked and autosomal mus loci. In general, mutations that are strongly sensitive to MMS are also sensitive to one or both of the procarcinogens, AAF and BP, as opposed to HN2 and gamma-radiation. In contrast, the moderately MMS sensitive mutations are sensitive to HN2 and gamma-rays, but not to AAF or BP. Of the 14 mus strains that are not sensitive to MMS, 5 are sensitive to AAF, another 5 are sensitive to HN2, and the remaining 4 are sensitive to gamma-rays. PMID- 3102957 TI - Studies on mutagen-sensitive strains of Drosophila melanogaster. X. Repair of radiation-induced DNA damage in primary cell cultures after irradiation with X rays. AB - The repair of X-ray-induced DNA lesions in repair-deficient mutant strains was studied as a way of investigating the mechanism of the induction of genetic damage. Genetic effects on the recovery of X-ray-induced damage by the repair deficient strains ebony (photoreactivation repair-deficient) and mus(1)101D1 (post-replication repair-deficient) were interpreted as impaired repair of single and double-strand DNA breaks. We investigated the repair of X-ray-induced DNA breaks and alkaline-labile sites in primary cell cultures of ebony and mus(1)101D1 and in cultures of their control strains. No significant differences were found between the repair rates in the mutants and control strains. This indicates that the genetic effects of these mutants are not due to an impaired rate of repair of DNA breaks. PMID- 3102958 TI - Induction of SOS responses in Escherichia coli by 5-fluorouracil. AB - The inducibility of SOS responses by 5-fluorouracil (5-FU), which has been used as an antitumor drug, was studied in Escherichia coli cells which have different DNA repair capacities for UV lesions. Expression of the umuC gene was apparently induced by 5-FU in the wild-type and uvrA strains, but not in lexA and recA strains. The inducibility of the umuC gene by 5-FU, the metabolite of which inhibits thymidylate synthetase, was abolished in cultures containing deoxythymidine monophosphate which is converted from deoxyuridine monophosphate by thymidylate synthetase. These results suggest that 5-FU may exert its SOS inducibility by inhibiting thymidylate synthetase and then disturbing DNA metabolism but not by incorporating 5-FU residues into RNA. Further, 5-FU weakly induced mutations in E. coli. PMID- 3102959 TI - Mutagenic activity of fluorides in mouse lymphoma cells. AB - The L5178Y mouse lymphoma cell forward-mutation assay was used to test for the mutagenic activity of sodium and potassium fluoride at the thymidine kinase locus. Mutants were detected by colony formation in soft agar in the presence of trifluorothymidine. Mutagenic and toxic responses were observed in the concentration range of 300-600 micrograms/ml with both sodium and potassium fluoride. Approximately 3-fold increases in mutant frequency were observed for concentrations in the 500-700 micrograms/ml range that reduced the relative total growth to approximately 10% in the absence or presence of a rat-liver S9 activation system. A sample of 30% sodium fluoride-70% sodium bifluoride (NaHF2) induced a similar mutagenic response but was more toxic with respect to the fluoride concentration. A specificity for fluoride ions in causing mutagenesis was indicated by the fast that much higher concentrations of sodium or potassium chloride were necessary to cause toxicity and increases in the mutant frequency. The possible involvement of chromosomal changes was signaled by the predominant increase in the small colony class of mutants. PMID- 3102960 TI - Effects of anticoagulants upon sister-chromatid exchanges, cell-cycle kinetics, and mitotic index in human peripheral lymphocytes. AB - The effects of 3 blood anticoagulants, heparin, acid citrate dextrose (ACD), and ethylenediaminetetraacetic acid (EDTA) were investigated using human peripheral lymphocytes. Three different endpoints were examined: sister-chromatid exchange (SCE), cell kinetics index (CKI), and mitotic index (MI). SCEs were significantly increased in cells treated with EDTA, while the CKI and MI were significantly decreased in cultures treated with either ACD or EDTA when compared to cultures treated with heparin. These results suggest that anticoagulants may produce undesired effects upon cultured cells and indicate that the type of anticoagulant should be considered carefully prior to commencing cytogenetic studies using human peripheral lymphocytes. PMID- 3102961 TI - Paramyotonia congenita: successful treatment with tocainide. Clinical and electrophysiologic findings in seven patients. AB - Seven patients with paramyotonia congenita (PC) from two families were studied. Voluntary exercise of the hand muscles was performed at different hand temperatures, both before and after treatment with tocainide. All patients developed stiffness, prolonged weakness, and small compound muscle action potentials (CMAPs) following exercise; the temperature at which this occurred was individually different. Two patients with PC and associated episodes of generalized weakness underwent potassium loading. A prolonged exercise test was performed both immediately before and 90 minutes after K-loading. Exercise induced weakness and CMAP-decline occurred only with high serum K levels. Thiazide treatment in these two patients was ineffective. All seven patients responded well to tocainide. Treatment response and side effects were dose dependent. Good clinical improvement has been maintained in all patients for more than 6 months, with relatively small doses of tocainide (400-1200 mg/day). PMID- 3102962 TI - Isolated growth hormone deficiency after cerebral edema complicating diabetic ketoacidosis. PMID- 3102963 TI - Absence of hepatitis after treatment with a pasteurized factor VIII concentrate in patients with hemophilia and no previous transfusions. AB - Post-transfusion hepatitis is frequent among patients with hemophilia who are treated with concentrated factor VIII prepared from pooled plasma, especially if it is obtained from paid donors. In 26 patients with hemophilia A or von Willebrand's disease who had not been treated with blood or any blood product and hence were highly susceptible to the development of post-transfusion hepatitis, we infused 32 batches of a factor VIII concentrate that had been produced from large pools of human plasma (collected from paid plasmapheresis donors) and then heated in solution at 60 degrees C for 10 hours before final lyophilization. Patients were examined clinically and serologically over a period of 12 months after the first infusion of the pasteurized concentrate. Neither hepatitis nor serologic signs of other viral infections were observed. The hemostatic effectiveness of the concentrate appeared to be satisfactory relative to untreated concentrates. PMID- 3102964 TI - Familial properdin deficiency and fatal meningococcemia. Correction of the bactericidal defect by vaccination. PMID- 3102965 TI - Subjective indicators of nitroglycerin potency. PMID- 3102966 TI - A T-cell receptor gamma/CD3 complex found on cloned functional lymphocytes. AB - Cloned blood lymphocytes that do not express the alpha- and beta-chains of the T cell receptor show MHC-unrestricted cytotoxicity. These cells carry the gamma protein, disulphide-linked either to another molecule or to itself, and associated with the CD3 complex. These observations may help to solve the mystery posed by the discovery of the gamma gene. PMID- 3102967 TI - Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes. AB - The T-cell receptor (TCR) gamma polypeptide is expressed associated with CD3 (T3) on the surface of normal human peripheral blood lymphocytes. These cells function as non-MHC-restricted cytotoxic T lymphocytes (CTL)and thus may play an important role in host immune defence. The TCR gamma polypeptide occurs as a dimer in at least two molecular forms based on the absence or presence of disulphide linkage. These forms use TCR gamma polypeptides with strikingly different peptide backbone sizes. PMID- 3102968 TI - A gamma-chain complex forms a functional receptor on cloned human lymphocytes with natural killer-like activity. AB - We have recently derived from human fetal blood (25 wks) a series of cloned cell lines that were selected for their ability to kill the conventional natural killer (NK) target cell K562. It was found that a fraction of these clones express CD3 proteins but not the monomorphic Ti alpha beta determinant recognized by WT31 antibody. One interleukin-2-dependent CD3+ WT31- clone, termed F6C7, was used for immunization of mice to generate monoclonal antibodies directed at a potentially novel recognition receptor. It was shown that F6C7 cells, which transcribe Ti beta but not Ti alpha genes, surface-express a clonotypic structure, termed NKFi. Immunoprecipitations performed with anti-NKFi monoclonal antibody (mAb) indicated that the corresponding molecule is resolved in SDS polyacrylamide gel electrophoresis (PAGE) as a single band of relative molecular mass approximately 85,000 (Mr approximately 85K). After reduction, a major band was detected at 44K and a faint band was present at 41K. The present study was designed to characterize this structure. It was found that NKFi represents either two 44K disulphide-linked gamma (TCR) chains, or possibly one gamma chain associated to an additional undetected molecule, and that the 41K material corresponds to a partially glycosylated fraction of the gamma protein. Anti-NKFi mAb both induces a specific autocrine proliferative response and blocks cytotoxic function, demonstrating that gamma chains serve as functional receptor structures on subpopulations of normal human lymphocytes. PMID- 3102969 TI - Structure of co-crystals of tropomyosin and troponin. AB - Troponin, a Ca2+-sensitive complex, regulates the motions of tropomyosin on the thin filaments in many muscles. It has three subunits, each with a different architecture and function: TnC binds Ca2+; TnI binds to actin and inhibits contraction; and TnT binds one complex to each tropomyosin molecule. The troponin complex has an elongated shape with TnC and TnI forming a globular 'head' region and TnT a long (approximately 160 A) 'tail'. TnT binds to two widely separated regions of tropomyosin: the head region of the complex is near Cys 190 of tropomyosin and the tail region is near the overlapping joint that links the tropomyosin molecules into filaments. Here we report the X-ray structure determination at 17 A resolution of glutaraldehyde-treated tropomyosin crystals in which native troponin complex or fragments of TnT have been bound. Our results show that the amino-terminal tail end of TnT spans the head-to-tail joint of the tropomyosin filaments, and that the 'head' region of the whole troponin complex binds approximately 200 A away near residues 150-180 of the tropomyosin molecule. PMID- 3102970 TI - A family of unusually spliced biologically active transcripts encoded by a Drosophila clock gene. AB - Complementary DNA cloning of the transcripts of the Drosophila clock gene period reveals three distinct transcripts. These result from unusual splicing pathways, one involving a CG 3' splice site and one resulting in the use of two different reading frames in one exon, and they predict three separate proteins. Two of the cloned cDNAs can restore clock function to mutant arrhythmic flies. PMID- 3102971 TI - Differential expression of two distinct T-cell receptors during thymocyte development. AB - The product of the T-cell receptor (TCR) gamma-gene has recently been found to be expressed on a subset of both peripheral cells and thymocytes. As an initial approach to understanding the role of this gamma-chain of TCR (TCR gamma) in T cell development, we have studied the ontogeny of TCR expression at the protein level in the developing murine thymus. We show here that the first T3-associated TCR to be expressed in the developing thymus is a disulphide-linked heterodimer composed of a gamma-chain of relative molecular mass 35,000 (Mr 35K) and a 45K partner (termed TCR delta). This TCR gamma delta is first detected approximately two days before the appearance of cell-surface TCR alpha beta heterodimers. We report that N-glycosidase digestions reveal that all of the gamma-protein expressed on fetal thymocytes, as in adult CD4-8-(L3T4-, Lyt2-) thymocytes, bear N-linked carbohydrate side chains. The major gamma-gene transcribed in mature, alpha beta-bearing T cells (V gamma 1.2C gamma 2)encodes no N-linked glycosylation site so these results suggest that the fetal gamma delta receptor defines a distinct T-cell lineage whose development in the thymus precedes classical alpha beta-bearing cells. PMID- 3102972 TI - Characterization of murine thymocytes with CD3-associated T-cell receptor structures. AB - The thymus is the major site for T-cell receptor (TCR) gene rearrangement and T cell maturation. The specific antigen recognition structure (TCR) on murine T cells has been shown to be dependent on a polymorphic set of disulphide-linked heterodimers, containing two integral membrane glycoprotein chains, TCR alpha and TCR beta, expressed in non-covalent association with an invariant complex of proteins, CD3 (T3). Recently, a novel TCR/CD3 complex, that includes the product of the TCR gamma gene, has been identified on a subset of both peripheral cells and thymocytes. Here we examine the expression of TCR/CD3 complexes in fetal ontogeny and in the adult thymus. The results demonstrate that CD3+4-8-(T3+,L3T4 ,Lyt2-)cells are detected in day-15 fetal thymi, throughout fetal development and in adult thymus. In situ hybridization studies indicate that these early CD3+ cells express high levels of TCR gamma-specific RNA, low levels of TCR beta specific RNA and no detectable TCR alpha-specific RNA. Day-16 CD3+,4-,8- fetal thymocytes can be activated to proliferate and demonstrate cytolytic activity when cultured in the presence of anti-CD3 monoclonal antibodies and interleukin-2 (IL-2). These results suggest that CD3-bearing cells, present early in thymic ontogeny, express a functional TCR and may, therefore, be important in repertoire development. PMID- 3102973 TI - Characterization of an expressed CD3-associated Ti gamma-chain reveals C gamma domain polymorphism. AB - The majority of human T cells express an antigen receptor consisting of a disulphide-linked heterodimer (Ti) of relative molecular mass 80,000-90,000 (Mr 80-90K) which is noncovalently associated with a set of at least three proteins of Mr 20-28K termed CD3 (Leu4, T3). Whereas both chains of Ti, an acidic alpha chain of Mr 48-54K and a more basic beta-chain of Mr 40-44K, contain variable and constant region domains, the component peptides of CD3 are invariant. Several laboratories have more recently reported the expression of CD3 in association with a novel protein. On the surface of long-term T-cell lines and one thymocyte clone this novel structure consists of a 40K protein noncovalently linked to a 55 or 62K protein identified as the protein product of the Ti gamma-chain gene, a T cell specific gene which like the Ti alpha- and Ti beta-chain genes undergoes rearrangement of variable (V) and joining (J) region gene segments. On the human T-cell leukaemic line PEER we have detected only a single 55K glycoprotein associated with CD3. We here demonstrate that an anti-Ti gamma-peptide antiserum reacts with the 55K CD3-associated protein on PEER. Most previously described human Ti gamma-chain complementary DNA clones encode the products of non functional rearrangements. One of the Ti gamma cDNAs isolated from PEER, however, represents a functional rearrangement reported for the first time in a cell which expresses a Ti gamma-chain protein product on the cell surface. Interestingly, a 48-base-pair (bp) sequence in the constant (C) region domain of this functional Ti gamma-chain cDNA is triplicated in PEER and duplicated in other cDNAs isolated from PEER and other cell lines. PMID- 3102974 TI - The molecular clock runs more slowly in man than in apes and monkeys. AB - The molecular clock hypothesis postulates that the rate of molecular evolution is approximately constant over time. Although this hypothesis has been highly controversial in the past, it is now widely accepted. The assumption of rate constancy has often been taken as a basis for reconstructing the phylogenetic relationships among organisms or genes and for dating evolutionary events. Further, it has been taken as strong support for the neutral mutation hypothesis, which postulates that the majority of molecular changes in evolution are due to neutral or nearly neutral mutations. For these reasons, the validity of the rate constancy assumption is a vital issue in molecular evolution. Recent studies using DNA sequence data have raised serious doubts about the hypothesis. These studies provided support for the suggestion made from immunological distance and protein sequence data that a rate slowdown has occurred in hominoid evolution, and showed, in agreement with DNA hybridization studies, that rates of nucleotide substitution are significantly higher in rodents than in man. Here, rates of nucleotide substitution in rodents are estimated to be 4-10 times higher than those in higher primates and 2-4 times higher than those in artiodactyls. Further, this study provides strong evidence for the hominoid slowdown hypothesis and suggests a further rate-slowdown in hominoid evolution. Our results suggest that the variation in rate among mammals is primarily due to differences in generation time rather than changes in DNA repair mechanisms. We also propose a method for estimating the divergence times between species when the rate constancy assumption is violated. PMID- 3102975 TI - Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand. AB - Activation of resting T lymphocytes is initiated by the interaction of cell surface receptors with their corresponding ligands. In addition to activation through the CD3 (T3)-Ti antigen-receptor complex, recent experiments have demonstrated induction of T-cell proliferation through the CD2 (T11) molecule, traditionally known as the erythrocyte(E)-receptor, through which T cells can bind red blood cells (RBC). This 'alternative pathway' of T-cell activation was observed in vitro in response to combinations of anti-CD2 monoclonal antibodies (mAbs) that bind to distinct epitopes of CD2, such as mAbs against T11(2) plus T11(3). The physiological importance of this activation pathway can be assessed only by studying the effects of a naturally occurring ligand of CD2 on T-cell activation. We have recently described such a ligand, a glycoprotein of apparent relative molecular mass 42,000 (Mr 42K) that is expressed on all blood cells and some other tissues. Here we demonstrate that binding of this cell surface molecule, termed T11 target structure or T11TS, to CD2 (T11) induces reactivity in resting T cells to a mitogenic stimulus given by a mAb to the T11(3) determinant or by submitogenic concentrations of anti-T11(2+3) mAbs. Thus, one of the signals required for T-cell activation through the alternative pathway is provided by the interaction of CD2 with a naturally occurring complementary cell surface molecule. PMID- 3102977 TI - Comparison of pharmacokinetics of radiolabeled monoclonal antibody UJ13A in patients and animal models. AB - The antigen to which the monoclonal antibody UJ13A binds is expressed by normal primate brain and most tumors of neuroectodermal origin. The antibody has been used in radioimmunologic studies in patients with neuroblastoma and glioma, though the uptake of antibody into tumors is low. Animal models have been sought to allow definition of the parameters that influence tumor uptake. Animals include nude mice, in which xenografted human tumors can be studied, and marmosets, in which the primate response to exposure to murine antibodies can be investigated. This presentation reports the preliminary pharmacokinetic data from studies of mice and marmosets and compares the data with those obtained in patients. PMID- 3102976 TI - HLA class II induction in human islet cells by interferon-gamma plus tumour necrosis factor or lymphotoxin. AB - HLA class II molecules are surface glycoproteins which are essential in the initiation of immune responses. It has been postulated that induction of class II in epithelial cells such as endocrine cells, which are normally class II negative, may result in autoimmunity. In type I diabetes, islet beta cells, the target of the autoimmune process, selectively express class II antigens. But in contrast to most other cell types, islet beta cells are not stimulated to express class II by interferon-gamma (IFN-gamma) and thus the conditions under which this induction occurs have been particularly elusive. The cytotoxins tumour necrosis factor (TNF) and lymphotoxin (LT) synergize with IFN-gamma in a number of activities. We report here that IFN-gamma in combination with either TNF or LT induces islet cell class II expression. This finding has important implications for the pathogenesis of type I diabetes and the understanding of the differential control of class II expression. PMID- 3102978 TI - Thimerosal induces endothelium-dependent vascular smooth muscle relaxations by interacting with thiol groups. Relaxations are likely to be mediated by endothelium-derived relaxing factor (EDRF). AB - The sulfhydryl reagent thimerosal, as well as acetylcholine and Ca2+-ionophore A23187, produced concentration-dependent relaxations of intact rabbit aortic strips. The ability of strips to relax in response to these agents was dependent on the presence of vascular endothelium. Purposely removing the endothelium led to a complete loss of the relaxation responses. Thimerosal was at least as efficacious as A23187 in inducing endothelium-dependent relaxations, but its relaxations developed much slower than those induced by A23187 or acetylcholine. A small concentration of thimerosal that had no appreciable effect by itself, potentiated the relaxing response to acetylcholine in endothelium-intact preparations. Endothelium-dependent relaxations induced by larger concentrations of thimerosal, as well as relaxations produced by acetylcholine, were inhibited by the antioxidant and lipoxygenase inhibitor nordihydroguaiaretic acid, by haemoglobin, and by the inhibitor of soluble guanylate cyclase methylene blue. Indomethacin had no effect on these relaxations. The thiol compounds glutathione, 2-mercaptoethanol and a low concentration of dithiothreitol prevented (and reversed) relaxations induced by thimerosal, but had little or no effect on ACh relaxations. A high concentration of dithiothreitol also markedly inhibited the ACh relaxation. These results are consistent with the hypothesis that thimerosal stimulates endothelial cells to produce a relaxing substance whose properties are similar or the same as those of the endothelium-derived relaxing factor (EDRF) released in response to acetylcholine or A23187. The biochemical mechanism by which thimerosal induces the formation and/or release of this relaxing substance is likely to be different from ACh.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102980 TI - [The surgical treatment of acute pancreatitis]. PMID- 3102979 TI - The role of the paracellular pathway in the net transport of calcium across the colonic mucosa. AB - Concentration dependent calcium fluxes across the colon descendens of the rat were measured in a modified Ussing chamber. Mucosa (m) to serosa (s) calcium flux showed a saturable component, whereas s to m calcium flux was linearly related to the calcium concentration. At low calcium concentrations net absorption and at concentration above 2.5 mmol/l net secretion of calcium was observed. The results obtained from the unidirectional calcium fluxes when clamping the transepithelial electrical potential agree well with those of the concentration dependence of the calcium fluxes: Only m to s flux has a voltage independent component. Calcium s to m movement is totally voltage dependent. Diffusional s to m calcium flux is greater than the diffusional fraction of the m to s calcium flow. Dexamethasone, known to stimulate water absorption in the colon descendens by an activation of sodium transport, had no effect on the cellular mediated m to s calcium transport but significantly increased paracellular s to m flux parallel to that of the extracellular marker mannitol. This increase in paracellular s to m calcium and mannitol flux was completely abolished by amiloride, which is known to suppress the dexamethasone-induced stimulation in sodium and water absorption. The results demonstrate that the increased paracellular s to m calcium and mannitol flow is oppositely directed to the dexamethasone-induced net fluid movement as it could be expected on the basis of Ussing's "anomalous solvent drag" effect. PMID- 3102981 TI - [National mortality data and the cost of health care]. PMID- 3102982 TI - [Results of the Ewing test insufficient--then what?]. PMID- 3102983 TI - [Diagnosis of AL amyloidosis in the absence of detectable serum or urinary monoclonal component]. AB - A case of massive amyloidosis without detectable monoclonal Ig component either in serum or in urines on classical electrophoresis and without obvious plasma cell proliferation is reported. Immunohistochemical study of renal and bone marrow biopsies showed that amyloid deposits were specifically stained with the anti-lambda antiserum and that 92% of the plasma cells were also lambda positive. Immunofixation following electrophoretic analysis of serum and urinary proteins exhibited a monoclonal lambda light chain at an advanced stage of the disease. Simple but not routinely used techniques are therefore of great interest to characterize apparently idiopathic amyloidosis which could have therapeutic implications. PMID- 3102984 TI - L-[3H]lysine binding to rat retinal membrane: I. Quantitative determination and characterization of the binding sites. AB - A saturable reversible binding to membranes from rat retina has been found for L [3H]lysine. Specific binding is time, temperature and protein concentration dependent, and shows stereospecificity. The best computer fits of the experimental data are obtained with a receptor model based on two independent binding sites, of which only one site with a Kd value of 229.4 +/- 14.23 nM and a Bmax of 2.04 +/- 0.11 pmol/mg protein could be characterized satisfactorily. Several compounds included putative neurotransmitters have moderate or no affinity for L-lysine binding sites. A different pattern of distribution of L [3H]lysine binding sites is observed among various regions of the brain, with the highest density in the occipital cortex, and the lowest density in ponsmedulla. The existence of binding sites in rat retinal membranes for L-lysine, as well as in the areas involved in the visual pathway, suggests a role for this amino acid in the physiological mechanism of the visual function. PMID- 3102985 TI - L-[3H]lysine binding to rat retinal membrane: II. Effect of kainic acid, D,L alpha-aminoadipic acid, iodoacetic acid, and modification by dark-exposure. AB - The rat retina and the different brain regions contain membranes sites that bind L-lysine in the nanomolar range. These binding sites undergo changes in different experimental conditions, thus: intraocular injection of kainic acid induces a reduction of the density of L-lysine binding sites, D,L-alpha-aminoadipic acid injected into the eye enhances both kinetic parameters (Bmax and Kd) of L [3H]lysine binding sites, the intraperitoneal injection of iodoacetic acid decreases the sensitivity for its ligand binding sites, and the exposure to darkness of the rats reduces L-[3H]lysine binding in the retina, thalamus, hypothalamus and superior colliculus, but not in the occipital cortex; such a decrease appears to be characterized, at least in the retina, by a lower sensitivity of the binding sites for L-lysine after the exposure to darkness. The results show that L-lysine binding sites are located on kainic acid-sensitive cells and can be involved in the physiological mechanism of vision. PMID- 3102986 TI - [A study of regional cerebral blood flow before and after superficial temporal artery-to-middle cerebral artery anastomosis]. AB - Regional cerebral blood flow (rCBF), using a single photon emission CT with Xe 133 inhalation method, was measured before and after the operation in 30 patients who underwent a superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. The purpose of this study is to assess the effect of STA-MCA anastomosis from the standpoint of hemodynamics and the results obtained were as follows: rCBF at rest increased after the operation, which was approximately 10% alterations and was localized in temporal region of operated hemisphere and frontal region of non-operated hemisphere respectively. rCBF during STA compression test after surgery decreased only in temporal region (anastomotic site) of operated hemisphere. This findings might indicate that blood flow via the bypass artery become to provide mainly to the confined area. CO2 reactivity was disturbed in 6 patients before operation, but it restored in 4 patients after operation. Autoregulation was also abolished in 8 patients before operation, but it restored in 6 patients after operation. In the group of severe degree of ischemia, however, autoregulation did not show the tendency to recover after the operation, whereas CO2 reactivity somewhat recovered. Angiographical retrograde filling which indicates collateral circulation reduced or disappeared in 12 out of 14 patients, in which postoperative rCBF in temporal region increased, in addition autoregulation and CO2 reactivity tended to recover after the bypass operation. These data mentioned above probably indicated the influences of CBF increase via the bypass artery. In summary, it might be concluded that the hemodynamic change such as disappearance of collateral circulation seen on angiography, additionally postoperative rCBF increase in anastomotic site seemed to be related to the restoration of these vascular responses such as CO2 reactivity and autoregulation in ischemic brain. PMID- 3102987 TI - [A case of primary interhemispheric subdural abscess]. AB - A rare case of primary interhemispheric subdural abscess is reported. This 13 year old boy, who had had high fever for 2 days, was brought into the hospital by an ambulance. He was disoriented and mild stiffness of the neck was noted. A Jacksonian seizure that began in the left leg occurred immediately after admission. The initial CT scan showed no apparent abnormality. His clinical signs and spinal fluid findings showing slight monocytic response and normal sugar content suggested viral meningo-encephalitis. The patient was given steroid and glyceol to control the intracranial pressure and antibiotics was also given. The convulsions disappeared with anticonvulsants and the patient became afebrile on the 7th hospital day. He was discharged on the 53rd hospital day without any neurological deficit. But, he was re-admitted because of recurrence of the convulsion 29 days after the discharge. The CT scan revealed an interhemispheric (rt parafalcial) abscess and the drainage of abscess was performed through a craniotomy. The post-operative course was satisfactory and he was discharged on 33rd post-operative day. It is easy to diagnose the primary interhemispheric subdural abscess on CT scan at the advanced stage. However, it may be difficult to make definite diagnosis at its acute phase and it is important not to miss some characteristic clinical features of the interhemispheric abscess that can be safely cured by appropriate surgical treatment. PMID- 3102988 TI - [Surgical treatment of convexity focal epilepsy--based on diagnosis of PET and subdural EEG]. AB - The most important premise for a successful surgical treatment of epilepsy lies in an accurate diagnosis of the focus location. The hitherto employed methods for this purpose are meticulous analysis of seizure contents and scalp EEGs, but spatial localization of the focus sites is far beyond the capacity of these diagnostic measures. With the advent of positron emission tomography (PET), in vivo observation of human brain metabolism has become possible. The indices of brain metabolism such as cerebral blood flow (rCBF), cerebral metabolic rate of glucose or oxygen (CMRG, CMRO2) are noninvasively measured by PET offering priceless information for diagnosing brain dysfunction such as ischemia, degeneration, psychosis, or epilepsy. Kuhl et al. first employed PET in assessment of epileptic foci, in which interictal foci were beautifully detected as discrete "hypometabolic zones". Many researchers have confirmed this invaluable finding, and nowadays PET seems to have acquired the citizenship as one of the most capable diagnostic measures in focus localization. We have hitherto applied PET study in 72 epileptic patients. The main contents of their seizures consists of complex partial in 32, elementary partial in 32, generalized in 6, and others in 3 cases. We administered perorally 10 mCi glucose labeled with C11 produced in the JSW Baby Cyclotron for the study of CMRG. The continuous inhalation method of CO2 and O2 labeled with O15 produced in the same cyclotron was also employed for measurement of rCBF and CMRO2. In both studies, epileptic foci were shown as well demarcated hypometabolic zones with decreased CMRG, rCBF or CMRO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102989 TI - [Arachnoiditis ossificans after repeated myelographies and spinal operations--a case report and review of the literature]. AB - A 58-year-old female was admitted because of lumbago and dysesthesia on the lateral aspect of the left leg. She had myelographies and spinal operations 4 years ago. Metrizamide myelogram on admission revealed the findings of adhesive arachnoiditis. During operation, four plaques involving the cauda equina were found, removed and histologically proved to be osseous tissue. In reviewing the previously published cases of arachnoiditis ossificans, it is divided into two forms. One is incidentally found in the arachnoid membrane at the time of an autopsy or spinal operation. The other is a progressive form causing impairment of the spinal cord and cauda equina. Compared with the former, the latter is extremely rare. At present, there appears to be a general agreement about the pathological process to ossification in the latter. The ossified plaque has its origin in meningothelial cell clumps located at the junction of the arachnoid sheet and the trabecula. The ossification occurs secondarily as a result of degenerative change in these clumps after myelography, spinal operation, subarachnoid hemorrhage, spinal trauma and spinal anesthesia. In our case, it is presumed that repeated spinal operations or myelographies played a role as a trigger toward ossification. PMID- 3102990 TI - Decreased stimulation of adenylate cyclase by growth hormone-releasing factor in the anterior pituitary of old rats. AB - Adenylate cyclase activity was studied in anterior pituitary homogenates from young adult (6 months) and old (20 and 24 months) male rats. Basal, NaF-, GTP-, 5'-guanylimidodiphosphate (Gpp(NH)p)- and forskolin-stimulated activities were similar in the three groups, implying that the stimulatory guanyl nucleotide regulatory binding site (NS) and the catalytical unit were unaffected by aging. Vasoactive intestinal peptide (VIP)-stimulated adenylate cyclase activity was also identical in the three groups. The efficacy (i.e., the maximum effect) of growth hormone-releasing factor [GRF(1-29)-NH2] on adenylate activity was reduced by 45-49% in old and senescent rats with no change in peptide potency (i.e., the concentration required for half-maximal enzyme stimulation). These results suggest that aging induced a selective loss of functional GRF receptors but influenced neither the coupling between receptors, NS and the catalytic unit nor the efficacy of the catalytic unit per se. PMID- 3102991 TI - Effect of thyrotropin-releasing hormone on growth hormone release in normal subjects pretreated with human pancreatic growth hormone-releasing factor 1-44 pulsatile administration. AB - Growth hormone (GH) increase after thyrotropin-releasing hormone (TRH) has been documented in many pathological conditions. In order to evaluate whether exposure to growth hormone-releasing factor (GRF) might contribute to this effect in normal subjects, we studied GH responses to placebo, TRH, GRF and GRF plus TRH either in basal condition or after GRF administration. Ten subjects received placebo, TRH, GRF and GRF plus TRH on four separate occasions. GRF induced a clear rise in plasma GH, statistically different from those obtained after placebo or TRH (p less than 0.01). TRH was completely ineffective in both stimulating GH release and amplifying the secretory GH response to GRF. Twenty subjects, subdivided in four groups, received 3 consecutive intravenous GRF boli at two-hour intervals. Two hours later they were given a fourth stimulus: 5 had another 25 micrograms GRF i.v., 5 had 200 micrograms TRH i.v., 5 were tested with simultaneous 25 micrograms GRF and 200 micrograms TRH i.v. injection, and 5 with 1 ml saline. GH secretory responses were quantitated by determining the net incremental area under the curve (nAUC) over 60 min after the administration of each stimulus. The pattern of GH secretion after 1-3 GRF boli was not statistically different among the four groups. Plasma GH nAUC was higher after the first GRF injection than after the following ones (p less than 0.01). The administration of a fourth GRF bolus also caused a GH increase which was significantly smaller than that after the first one (p less than 0.01), but greater than that after placebo (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3102992 TI - Analgesic and convulsant effects of guanidinoethylmercaptosuccinic acid (GEMSA)- a potent enkephalin convertase inhibitor. AB - We studied behavioral effects of the intraventricularly and intrathecally administered guanidinoethylmercaptosuccinic acid (GEMSA) - a potent inhibitor of enkephalin convertase. When given intraventricularly in doses of 3 and 6 micrograms, GEMSA elicited analgesia; after doses of 12.5 and 25 micrograms the explosive motor behavior and convulsions occurred. Following the intrathecal administration of GEMSA (12.5, 25 and 50 micrograms), an increase in the tail flick latency was observed; moreover that drug potentiated analgesic effects of the intrathecally applied Met5-enkephalin-Arg6-Phe7 and Met5-enkephalin-Arg6-Gly7 Leu8. All the above effects of GEMSA were significantly attenuated by naloxone. The rats subjected to chronic pain showed a weaker analgesic response to the intrathecally injected GEMSA. The 3H-GEMSA binding to enkephalin convertase in the spinal cord of these rats produced only a slight increase in KD; besides, no changes in the enzyme activity were observed. The study shows that GEMSA has a potent pharmacological action in the central nervous system. Furthermore, this effect is partly due to the influence of GEMSA on endogenous opioid peptide systems, possibly on proenkephalin A. PMID- 3102993 TI - Enkephalin convertase in the rat spinal cord. AB - 3H-Guanidinoethylmercaptosuccinic acid (3H-GEMSA) a very selective inhibitor of enkephalin convertase, binds to the crude rat spinal cord homogenates saturably, reversibly and with high affinity. Scatchard analysis revealed two classes of binding sites with KD: 4.5 nM and 215 nM. A plot of dissociation experiment was nonlinear with the T1/2: 2 min and 6 min, respectively. 3H-GEMSA binding sites are evenly distributed throughout the rat spinal cord and their high density might suggest a physiological significance of enkephalin convertase in that tissue. PMID- 3102994 TI - Specific and nonspecific neuronal mechanisms of learning. PMID- 3102995 TI - Neuronal mechanisms of goal-directed behavior in monkeys. PMID- 3102996 TI - Interrelationship of the circadian and ovulatory rhythms of secretion of sex and gonadotropic hormones in intact and neonatally androgenized female rats. PMID- 3102997 TI - Axon development in mouse cerebellum: embryonic axon forms and expression of synapsin I. AB - A fundamental question in central nervous system development is the timing of synaptogenesis in relation to invasion of targets by afferent axons. A related question is how growth cones transform into synaptic terminals. These two aspects of axon maturation were examined in developing mouse cerebellum, by labeling single axons with horseradish peroxidase, to study their form and cytology, and by immunocytochemical staining of a synaptic vesicle antigen, synapsin I, a phosphoprotein found on synaptic vesicles in all mature CNS synapses. From embryonic day 16 to postnatal day 3, horseradish peroxidase-labeled afferent axons extend well into the cerebellum and have simple forms. At embryonic day 16, axon growing tips are synapsin I-negative. Synapsin I is first expressed at embryonic day 17, and by embryonic day 18, fibers are stained throughout the cerebellum. Synapsin I expression coincides with a general increase in synaptic specializations, although growing tips continue to have the cytology of growth cones. During the period that axons have primitive shapes, synapsin I is distributed throughout the terminal arbor, corresponding to the presence of small vesicles along neurite lengths, even at non-synaptic sites. After postnatal day 3, when synaptic terminals develop into stereotypic shapes and engage in characteristic synaptic relations, synapsin I is restricted to boutons. Thus, the synapse-specific protein synapsin I is expressed in fetal mouse brain, long before nerve endings have the structure and connections of adult brain. In cerebellar axons, the expression of this protein follows axon arrival, coincides with the appearance of elementary synapses, and accompanies the transformation of growing tips into stereotypic synaptic boutons. The time course of expression of synapsin I, a phosphoprotein that may be involved in synaptic efficacy, suggests that transmitter release may influence early axon-target cell interactions. PMID- 3102998 TI - Valproic acid hepatic fatalities: a retrospective review. AB - We reviewed all US cases of fatal hepatotoxicity coincident with valproate anticonvulsant therapy that were reported between 1978 and 1984. Thirty-seven hepatic fatalities were determined to have occurred coincident with the use of valproate. All but one patient had such other medical conditions as mental retardation, developmental delay, congenital abnormalities, and other neurologic diseases. The primary risk of fatal hepatic dysfunction (1/500) was found to be in children 0 to 2 years old receiving valproate as polytherapy. The risk declined with age and was low in patients receiving valproate as monotherapy (1/37,000). No hepatic fatalities occurred in patients above the age of 10 years receiving valproate as monotherapy. PMID- 3102999 TI - Limbic evoked potentials predict site of epileptic focus. AB - Limbic evoked potentials (LEPs) were recorded from intracerebral electrodes in the hippocampi of seven preoperative epilepsy surgery patients. LEPs were evaluated using amplitude, form, and asymmetry by raters blinded as to the side of electrographically proven seizure onset. Raters correctly predicted the side of focus in all four patients with proven unilateral temporal lobe seizure onset. Further, LEP amplitudes in two patients with bilateral independent temporal lobe seizure onset were markedly diminished compared with one patient with a nontemporal lobe seizure onset. LEP recordings may assist in determination of the site of epileptogenic pathology. PMID- 3103000 TI - Don't throw out the baby with the bathwater. PMID- 3103001 TI - Case for diagnosis. AIDS. PMID- 3103002 TI - Medical and infectious diseases in the theater of operations. PMID- 3103003 TI - Stress: an unnecessary fact of life. PMID- 3103004 TI - Vascular trauma. PMID- 3103005 TI - Strategies of biowarfare defense. PMID- 3103006 TI - Missile injuries: wound ballistics and principles of management. PMID- 3103007 TI - Medical defense against nerve agents: new directions. PMID- 3103008 TI - Cold injury complicating trauma in the subfreezing environment. PMID- 3103009 TI - Factors associated with stress fractures in military recruits. PMID- 3103010 TI - Gastrectomy for gastric ulcer. PMID- 3103011 TI - TURP followed by intraoperative hemorrhage incontinence. PMID- 3103012 TI - Learning from traditional combat mortality and morbidity data used in the evaluation of combat medical care. PMID- 3103013 TI - Case for diagnosis. AIDS. PMID- 3103014 TI - Cephalexin suspension for the treatment of skin infection in children. PMID- 3103015 TI - Data on human immunodeficiency virus (HIV) antibody testing among military recruits. PMID- 3103016 TI - HTLV-III/LAV infections in the military. PMID- 3103017 TI - Early evacuation of patients from the battlefield after laparotomy: experiences in Vietnam, Israel and the Falklands. PMID- 3103018 TI - Risk of injury in soldiers. PMID- 3103019 TI - Microcomputers as a management tool for hospital pharmacy directors. PMID- 3103021 TI - The application of strategic planning in the medical treatment facility. PMID- 3103020 TI - Chief complaints, contraceptive use and diagnoses of female soldiers in ambulatory GYN clinic. PMID- 3103022 TI - Penetrating craniocerebral injuries: observations in the Iraqi Iranian War. PMID- 3103023 TI - A prospective study of the etiology of hepatitis in the U.S. Army Wuerzburg community from 1978 to 1979. PMID- 3103024 TI - Occurrence of Baylisascaris procyonis in raccoon populations on military installations in the Washington, D.C. area. PMID- 3103025 TI - Pseudo-retrograde ventriculoatrial conduction and mid-diastolic filling waves noted on echocardiogram. PMID- 3103026 TI - Radiation induced osteosarcoma of the clavicle: a case report and literature review. PMID- 3103027 TI - Carpal bone malignancies. PMID- 3103028 TI - Efficacy of magnetic resonance imaging of the central nervous system: preliminary experience at a military referral center. PMID- 3103029 TI - Identification of two glycoproteins of chromaffin granules as the carboxypeptidase H. AB - An antiserum against carboxypeptidase H, an enzyme involved in the biosynthesis of neuropeptides such as the enkephalins, was used to identify the enzyme proteins in bovine chromaffin granules. Two-dimensional immuno- and lectin-blots revealed that two closely migrating glycoproteins which have been previously named J and K represented the enzyme. The same protein doublet was present in the membrane preparation and the soluble lysate of bovine chromaffin granules; however, the membrane contained significantly more enzyme protein. PMID- 3103030 TI - Induction of human leukocyte antigen-A,B,C and -DR on cultured human oligodendrocytes and astrocytes by human gamma-interferon. AB - gamma-Interferon (IFN-gamma) is known to induce expression of major histocompatibility complex (MHC) class II antigens on murine astrocytes and MHC class I antigens on murine oligodendrocytes. We studied whether the human IFN gamma could induce the expression of Human Leukocyte Antigen (HLA)-A, B, C and DR antigens on cultured human glia from autopsied brain white matter tissue. HLA A, B, C antigens were induced on both human astrocytes and oligodendrocytes, whereas HLA-DR antigens were induced only on some astrocytes. From these results, it is suggested that IFN-gamma affects the expression of MHC class I and class II antigens on astrocytes and oligodendrocytes derived from human brain. The relationship between the induction of MHC class I and class II antigens by IFN gamma and the pathogenesis of multiple sclerosis is discussed. PMID- 3103031 TI - Try this simple T.P.N. order form. PMID- 3103032 TI - A study of the chemical treatment of early caries of occlusal pits and fissures. PMID- 3103033 TI - Anticardiolipin antibodies: their presence as a marker for lupus anticoagulant in pregnancy. AB - A solid phase ELISA was developed to investigate the association between anticardiolipin antibodies and lupus anticoagulant in pregnancy. Twenty-seven pregnant women with a history of recurrent fetal losses or systemic lupus erythematosus (SLE) were tested for the presence of lupus anticoagulant, anticardiolipin antibodies, antinuclear antibodies (ANA) and anti-single-stranded DNA antibodies. Nineteen women with a total of 49 previous unsuccessful pregnancies were found to have lupus anticoagulant and anticardiolipin antibodies. Three women who had suffered four fetal deaths from six pregnancies had anticardiolipin antibodies without lupus anticoagulant. Cardiolipin antibodies were not detected in the remaining five patients. This assay for measuring anticardiolipin antibodies appears to provide a simple and inexpensive method of identifying women at risk of fetal death from the adverse effects of lupus anticoagulant. PMID- 3103034 TI - Stage IB cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy: role of adjuvant radiotherapy. AB - A retrospective review of 194 patients with stage IB cervical carcinoma treated with radical hysterectomy between January 1977 and December 1984 revealed 30 patients (15%) with pelvic node metastases. Twenty patients with pelvic node metastases received postoperative radiotherapy and ten patients did not. Five of 20 patients who received adjuvant radiotherapy had recurrence, compared with five of ten patients who did not receive radiotherapy. No pelvic recurrences occurred in the adjuvant radiotherapy group compared with two in the no radiotherapy group. Only one serious complication occurred in a patient receiving radiotherapy. Adjuvant postoperative radiotherapy may reduce pelvic recurrences and improve survival in patients with pelvic node metastases treated with radical hysterectomy and pelvic lymphadenectomy. PMID- 3103035 TI - Outpatient in vitro fertilization using transvaginal ultrasound-guided oocyte retrieval. AB - Of 80 patients who initiated in vitro fertilization cycles in an integrated outpatient facility, 61 had oocyte retrievals performed under local anesthesia with ultrasound-guided transvaginal aspiration of ovarian follicles. Ten patients conceived, all in the group of 49 who had human chorionic gonadotropin (hCG) timed retrievals. Our results indicate that in vitro fertilization can be performed to a high standard with this method, with excellent patient acceptance and reduced cost without general anesthesia, laparoscopy, or in-hospital setting. PMID- 3103036 TI - Considering a benefit-cost analysis framework for program evaluation. PMID- 3103037 TI - [Scanning electron microscopy of the effects of decalcifying agents on root canal dentin]. PMID- 3103038 TI - Relief of metastatic bone pain with etidronate disodium. PMID- 3103039 TI - Blast or boost? How the Joint Commission fared in the Institute of Medicine's nursing home study. PMID- 3103040 TI - Informed consent: myths and risk management alternatives. AB - The doctrine of informed consent, an enigma to many risk management personnel, is fuel for many malpractice claims. But the doctrine of informed consent is a rational, useful concept that can advance many of the goals of risk management. This article analyzes seven common "myths" or misperceptions about informed consent in relation to risk management and suggests five ways to address the risk management issues related to informed consent. PMID- 3103041 TI - A study to identify who is the responsible physician for each patient in a teaching hospital. AB - A one-day study was conducted to confirm evidence of disagreement about which physician was responsible for the care of patients in a teaching hospital. Sixteen percent of the patients reported the responsible physician as someone different from the physician listed on their medical record, and 13% could not provide any physician's name. Significant disagreement was also discovered between the name given by the charge nurse, the patient's identification band, and the face sheet on the patient's chart. Twenty-nine percent of the charts reviewed revealed no documented involvement by the responsible physician within the previous ten days. As a result of the study, the hospital changed its documentation procedures and the hospital and the medical school became aware of the need to improve monitoring of supervision of student physicians. PMID- 3103042 TI - Isolation and characterization of new glycolipids from Mycobacterium tuberculosis H37Rv. PMID- 3103043 TI - [Treatment of Rh-isoimmunized pregnant women with plasmapheresis]. PMID- 3103044 TI - The analgesic effect of tocainide in trigeminal neuralgia. AB - Tocainide is a derivative of lidocaine with anti-arrhythmic action and, unlike lidocaine, can be used for oral treatment. Tocainide was alternatively with carbamazepine given to 12 patients with trigeminal neuralgia in a double-blind cross-over study for 2 weeks. The analgesic effect was estimated each day by the patients using a 0-10-point scale summarizing the frequency and severity of the attacks. The similarity in analgesic effect of the two drugs was striking. A possible analgesic mechanism could be that tocainide blocks the sodium channels in the hyperexcitable nerve membranes in the pain-producing foci in trigeminal neuralgia. PMID- 3103045 TI - [Comparative efficiency of infecting laboratory animals via intravenous and subcutaneous administration of Schistosoma mansoni cercaria]. AB - Comparative study on effectiveness of intravenous and subcutaneous methods of infection of animals has shown that infection rate of helminths after the injection of equal dozes of cercariae under skin, into portal and femoral veins of golden hamsters does not differ significantly (42.6 +/- 4.2, 37.8 +/- 5.8 and 26.0 +/- 6.6 schistosomes, respectively). When using the above methods for cotton rats the infection rate was lower than that in golden hamsters. The most insignificant infection rate of parasites was recorded in both species after the injection of cercariae into the femoral vein. Results of the infection of golden hamsters with different dozes of cercariae have shown that with the increase of dozes of infectious material the infection rate of helminths rises during the experimental intestinal schistosomiasis only to a definite level, which is attained by the injection of cercariae into the portal vein in dozes lower than those used for subcutaneous infection. PMID- 3103046 TI - A life-cycle stage-specific antigen of Theileria parva recognized by anti macroschizont monoclonal antibodies. AB - Four monoclonal antibodies, raised against macroschizonts of Theileria parva, were studied to characterize their antigen binding specificity. The indirect fluorescent antibody test showed that the antigen(s) recognized were present in the macroschizont stage of the parasite life-cycle but not in piroplasm, kinete or sporozoite stages. Immunoblot analysis of macroschizont stage antigens suggested that all four antibodies recognized the same antigen. This was a molecule which varied in molecular mass between different parasite stocks, ranging from 68,000 to 95,000 Da. The antigen was localized by immunoelectron microscopy to the surface of the intracellular macroschizonts. PMID- 3103047 TI - The induction of species-specific immunity against Schistosoma japonicum by exposure of rats to ultra-violet attenuated cercariae. AB - Single percutaneous immunizations of Fischer rats with 1000 ultra-violet attenuated Schistosoma japonicum cercariae induced 52-88% resistance to challenge 4 weeks later. Increasing this to 3 immunizations induced 90% resistance to challenge, and this level of protection remained undiminished for up to 40 weeks after vaccination. Rats vaccinated with gamma-irradiated S. mansoni cercariae were resistant to challenge with S. mansoni but not S. japonicum. Similarly rats vaccinated with u.v.-attenuated S. japonicum cercariae were not resistant to heterologous challenge. Thus irradiated vaccines are species-specific in both permissive and non-permissive hosts. PMID- 3103048 TI - Studies on heterologous resistance between Schistosoma mansoni and Fasciola hepatica in inbred rats. AB - Fischer rats infected with Fasciola hepatica showed significant resistance to Schistosoma mansoni challenge, and vice versa, whereas immunization with 20 Krad irradiated S. mansoni cercariae failed to protect against F. hepatica challenge, but did protect against homologous challenge. When groups of rats received intraperitoneal implants of newly excysted juvenile flukes, 20- to 22-day-old juveniles, or 8- to 10-week-old flukes, none was significantly protected against S. mansoni challenge, whereas juvenile implants did protect against homologous F. hepatica challenge. In passive transfer experiments in rats, serum from F. hepatica-infected rats or rabbits protected recipients against homologous, but not heterologous challenge, and serum from rats vaccinated with 20 Krad irradiated S. mansoni cercariae protected recipients against homologous, but not heterologous challenge. These experiments provide evidence that the mechanisms involved in homologous and heterologous resistance are different, the latter lacking immunological specificity. Microsphere injections in F. hepatica-infected rats demonstrated 'shunting' from the portal system to the systemic circulation. If migrating schistosomula are also 'shunted' in Fasciola-infected rats, this, rather than immunologically specific effector mechanisms, might explain their failure to establish in the portal system. PMID- 3103049 TI - Pathologically induced alterations in the dimensions of the hepatic portal vasculature of mice infected with Schistosoma mansoni. AB - Alterations in the hepatic portal vasculature of NMRI mice infected with Schistosoma mansoni were assessed using a microsphere injection technique. The accumulation of eggs in the livers of infected mice and the development of portal hypertension were closely related to the worm pair burden during the first 15 weeks of infection. Individual variation between mice harbouring identical patent worm pair burdens was partially explained by the reduced fecundity of females from sexually biased infections. As eggs accumulated in the liver and portal hypertension increased, the number of injected microspheres escaping from the hepatic portal system rose in rank order of diameter from 9 microns through 15 microns and 25 microns to 50 microns. There was a strong correlation between the numbers of parasite eggs in the lungs and injected microspheres recovered from the lungs. The pattern of detection of microspheres in the lungs indicated a progressive increase in diameter of intra-hepatic porta-systemic connexions, followed by development of large-bore extra-hepatic collateral vessels. An accurate temporal profile of the pathological state of the host and the extent of collateral vessel formation was obtained. Injection of 141-Ce-labelled microspheres demonstrated that the arterial supply to all organs of the body was affected by alterations in the microvasculature of the liver and lungs. PMID- 3103050 TI - The relationship between pathology and resistance to reinfection with Schistosoma mansoni in mice: a causal mechanism of resistance in chronic infections. AB - The development of resistance in mice to reinfection with Schistosoma mansoni was recorded during an early chronic infection, and compared with hepatic portal pathological and vascular changes. The latter were assessed using a microsphere injection technique. The degree of acquired resistance was directly dependent on the patent worm burden and the time post-infection. Strong correlations were noted between the development of resistance and the appearance of parasite eggs in the lungs and spleens of infected hosts. Weaker associations were present between resistance and other aspects of the disease pathology, such as portal hypertension and organ weights. The appearance of injected microspheres in the lungs and spleens correlated well with the appearance of eggs in those organs and with the development of resistance. The levels of resistance had risen and microspheres were detected in the lungs, before the development of major extra hepatic, porta-systemic collateral vessels. It is concluded that intra-hepatic vascular alterations may be a causal factor in the development of resistance, preventing the sequestration of migrating schistosomula in the liver. It is estimated that as much as 70-75% of the recorded resistance can be attributed to this immunologically non-specific mechanism. PMID- 3103051 TI - [The use of antibiotics in complications of endodontic therapy (2). Chemotherapeutic principles in complications of endodontic therapy. Classification and clinical data]. PMID- 3103052 TI - [The use of antibiotics in complications of endodontic therapy (3)]. PMID- 3103053 TI - [Various pulp complications of exodontic treatment errors in conservative dentistry]. PMID- 3103054 TI - [Various periodontal complications of exodontic treatment errors in conservative dentistry]. PMID- 3103055 TI - [Morpho-pathogenetic correlations between periodontal diseases and various diseases of otorhinolaryngologic significance. Clinical-statistical study]. PMID- 3103056 TI - [Opportunities and obstacles in orthodontic treatment with activators and active orthopedic methods]. PMID- 3103057 TI - [Diagnostic and therapeutic indications in space maintenance]. PMID- 3103058 TI - [Sealants in prevention]. PMID- 3103059 TI - [The composition of dentifrice pastes]. PMID- 3103060 TI - [Factors affecting the image quality in a study of the maxillofacial region using nuclear magnetic resonance (1)]. PMID- 3103061 TI - [Iconographic documentation of possible artifacts in the imaging of the maxillofacial region using nuclear magnetic resonance (2)]. PMID- 3103062 TI - [Pathogenetic theories of the occurrence of dental caries in drug addicts]. PMID- 3103063 TI - [Physiopathological relations between mouth pathology and gastric diseases]. PMID- 3103064 TI - [Analysis of a few of the more important physical properties of restorative dental materials (I)]. PMID- 3103065 TI - [The caries detector]. PMID- 3103066 TI - [Determination of the precipitation of salivary salts (I)]. PMID- 3103067 TI - [Lining cements: study of the insulating properties]. PMID- 3103068 TI - [The design of various functional activators in gnatho-orthopedic therapy]. PMID- 3103069 TI - [New composites: microfilled composite resins]. PMID- 3103070 TI - [Pulp protection: new products]. PMID- 3103071 TI - [The use of composites in posterior restorations]. PMID- 3103072 TI - [Design of active methods in orthodontics]. PMID- 3103073 TI - [Indications and electrosurgical technics in pediatric dentistry]. PMID- 3103074 TI - [A case of combined endodontic, periodontic and prosthetic therapy]. PMID- 3103075 TI - [Rational analysis of the construction and use of stainless steel crowns in pediatric dentistry]. PMID- 3103076 TI - [Sterilization and recycling of instruments in dentistry]. PMID- 3103077 TI - [Effect on the oral mucosa following treatment with antineoplastic agents]. PMID- 3103078 TI - [The interception of malocclusion in childhood]. PMID- 3103079 TI - [The use of antibiotics in complications of endodontic therapy (1). Bacterial flora of the oral cavity and relative pathology of antibiotics]. PMID- 3103080 TI - [The ultrasensitive determination of TSH permits the prediction of the response to TSH in the TRH test]. AB - A new ultrasensitive TSH immunoradiometric assay (IRMA) using two monoclonal antibodies is now able to distinguish between euthyroid and hyperthyroid patients. The aim of this study was to compare data given by ultrasensitive basal TSH (IRMA) and by the response of TSH to TRH test considered until now as the more reliable test in case of mild or atypical hyperthyroidism. Basal plasma TSH levels were determined in euthyroid (n = 80), hyperthyroid (n = 30), hypothyroid (n = 14) and pituitary deficient patients (n = 8) before and 30 minutes after a TRH test (250 micrograms i.v.). A close linear correlation was found between basal and post-stimulative TSH levels. Normal TSH response ranged from 2 to 22 uU/ml. The sensibility and the specificity of these two parameters appeared comparable in the case of primary dysthyroidism; on the contrary basal TSH levels were not sufficient for the diagnosis of central hypothyroidism. In conclusion, excepted for pituitary deficiency, basal plasma TSH (IRMA) levels are accurate and sufficient in the evaluation of the thyroid function and make the TRH-test useless. PMID- 3103081 TI - Comparison of 51Cr EDTA clearance with formulae in the measurement of glomerular filtration rate. AB - The need exists for a fast and accurate method of estimating glomerular filtration rate (GFR). A number of nomograms and formulae which estimate GFR on the basis of a plasma creatinine level have appeared in the literature. We examined some of these nomograms and formulae and showed that when the formula published by Cockcroft and Gault was compared with the GFR as estimated by 51Cr EDTA clearance, the coefficient of correlation was better than 0.94. We also compared creatinine clearance with the Cockcroft and Gault formula, and the Siersbaek-Nielsen nomogram. In each case, the correlation coefficient was less than that for the Cockcroft and Gault-51Cr EDTA comparison. Because of the inherent difficulties in making accurate 24 h urine collections, and problems associated with 51Cr EDTA studies, it is suggested that the formula prediction of GFR is more reliable than a GFR estimate using a 24 h collection. PMID- 3103082 TI - Group D or group G streptococcal infection? PMID- 3103083 TI - Removing the mysteries of parenteral nutrition. PMID- 3103084 TI - The how-to's of home i.v. therapy. PMID- 3103085 TI - Dural ectasia as a cause of widening of the internal auditory canals in neurofibromatosis. AB - Patients with neurofibromatosis have an increased incidence of acoustic neuroma, which is often bilateral. We present three patients with neurofibromatosis and enlarged internal auditory canals secondary to dural ectasia, without associated acoustic neuromata. Air CT cisternography and Metrizamide CT cisternography was needed in differentiating dural ectasia from acoustic neuroma in two patients. PMID- 3103086 TI - Effects of the components of breast milk on mucosal enzyme activity of the newborn small intestine. AB - The effects of the aqueous phase of human breast milk on the disaccharidase activity of newborn rabbit small intestinal mucosal explants were studied in vitro culture. These explants continuously synthesized protein and normal morphology was maintained for the duration of the cultures. Addition of the aqueous phase resulted in significant increase of lactase (p less than 0.001) and maltase (p less than 0.01) concentrations in these organ cultures. This effect was dose dependent and was observed whether the organ biopsies were derived from fed or starved newborn rabbits. Further purification of the aqueous phase showed that the active ingredient exerting these effects was lactose. These studies suggest that lactose may have an important function in stabilization of newborn intestinal disaccharidase enzymes. PMID- 3103087 TI - A new case of purine nucleoside phosphorylase deficiency: enzymologic, clinical, and immunologic characteristics. AB - Deficiency of purine nucleoside phosphorylase (PNP) was detected in a 3-yr-old boy who was admitted for investigation of a behavior disorder and spastic diplegia. The urinary excretion of purines, analyzed by high-performance liquid chromatography, showed the presence of large amounts of (deoxy)inosine and (deoxy)guanosine and low uric acid levels. Analysis of the (deoxy)nucleotide pools of erythrocytes showed elevated levels of deoxyguanine nucleotides and NAD and decreased guanine nucleotides. PNP activity in red blood cells was 0.1-0.5% of normal on two occasions and undetectable on four later measurements. Furthermore no immunoreactive material could be detected in his red cell lysate using an anti-PNP antiserum. PNP activities in the red cells of the patient's parents were 35 and 50% of normal. The presence of (minor) residual PNP activity in the patient enabled the investigation of some enzyme properties after partial purification. No abnormalities could be detected in substrate affinity for inosine, heat stability, and electrophoretic properties. In the heterozygous parents no signs of a mutant enzyme could be found. The molecular specific activities of the parental enzymes were also normal, indicating that no immunoreactive material attributable to inactive-mutant enzyme subunits was present. A striking feature of the patient is the prevailing neurologic abnormalities presumably caused by the metabolic disorder. A severe lymphopenia exists; however, clinical symptoms of an immune deficiency did not become apparent until the age of 4 yr. PMID- 3103088 TI - Glutamine oxidation by developing rat small intestine. AB - Glutamine has been reported to be a major oxidative substrate in adult rat small intestine. The significance of glutamine by developing rat jejunal tissue slices and isolated mitochondria was determined. Jejunum slices from suckling rats actively oxidized glutamine at rates significantly greater than adult slices. Increasing the glutamine concentration (0.5-4 mM) in the assay increased glutamine by jejunum of suckling pups by 30% compared to a 100% increase in adult jejunum. Glutamine oxidation by isolated jejunal mitochondria was similar in suckling and adult rat. Glutamine oxidation by jejunum of suckling rat was increased in the presence of 5 mM glucose whereas adult glutamine oxidation was not affected by exogenous glucose. Glutamine inhibited glucose oxidation by jejunum of both suckling and adult rats. In adult jejunal homogenates alanine aminotransferase activity was 2-fold greater than in suckling animals. In the presence of 10 mM aminooxyacetate, a known inhibitor of alanine aminotransferase, glutamine oxidation by jejunum of suckling rat was inhibited by 95%, suggesting that alanine aminotransferase is a major metabolic pathway for the oxidation of glutamine. PMID- 3103089 TI - Streptococcal pharyngitis in the 1980s. AB - Streptococcal pharyngitis remains a common problem in children and adolescents. However, the incidence of acute rheumatic fever is now quite low except in developing countries. Proper management of streptococcal pharyngitis has contributed significantly to the decline in ARF. Penicillin treatment has clearly altered the natural history of streptococcal infection; the acute illness is shortened, risk of spread of infection is reduced, suppurative complications are prevented and ARF is prevented. Some cases of acute glomerulonephritis may be prevented. The decline in rheumatic fever has probably contributed to a greater interest in clinical benefits of therapy. Antigen detection tests appear promising for providing a more rapid bacteriologic diagnosis of streptococcal infection, which in turn permits prompt treatment. While penicillin has been the treatment of choice for four decades, a disturbing trend of increasing numbers of clinical relapses or recurrent infections has been noted in recent years. Alternative antibiotics, such as the oral cephalosporins, may now be superior to oral penicillin in terms of lessening the risk of relapse. This advantage must be weighed against other factors including cost effectiveness. The most pressing dilemma for the clinician is management of the patient with repeated episodes of acute streptococcal pharyngitis. Certain of these problem patients may benefit from a period of penicillin prophylaxis during the seasons when streptococcal infections are most prevalent. There is now agreement that posttreatment throat cultures need not be done in the child who remains asymptomatic following therapy. However, it is incumbent on the clinician to make certain that appropriate therapy is prescribed and that compliance with oral regimens of therapy is satisfactory in the management of the patient with acute streptococcal pharyngitis. PMID- 3103090 TI - Review of 59 patients hospitalized with animal bites. AB - We reviewed the charts of 59 pediatric and adult patients hospitalized because of animal bites (46 dog bites, 10 cat bites, 3 monkey bites). The bites of 40 of the 59 patients were infected at the time of admission. Gram-stained specimens correctly predicted the infecting bacteria in only 5 of 20 cases. Eighty-three percent of the bacterial isolates were penicillin-susceptible. Before admission 14 patients had received outpatient antibiotic prophylaxis and the infections in 11 of these 14 patients were caused by bacteria susceptible to the prophylactic antibiotic. Complications were more common if antimicrobial therapy had not been altered according to susceptibility testing results. Of the 59 patients 19 were admitted immediately after being bitten because of severe uninfected bites. Of these 19 patients 18 received prophylactic antibiotics and none developed a serious complication. PMID- 3103091 TI - Pyruvate dehydrogenase complex deficiency as a cause of subacute necrotizing encephalopathy (Leigh disease). AB - Leigh disease is a disorder with great clinical variability and for which diverse biochemical causes have been proposed. Clarification requires rigorous correlation of biochemical abnormalities with strict morphologic diagnosis; such an unambiguous association is the subject of this report. A patient with well documented clinical and biochemical pyruvate dehydrogenase complex deficiency is shown on postmortem examination to have the specific CNS pathology of Leigh disease. These findings, considered together with the aggregate data in the literature, suggest strongly that pyruvate dehydrogenase complex deficiency is the basic defect in a subgroup of patients with Leigh disease. PMID- 3103092 TI - Discounting an adverse maternal effect on severity of neurofibromatosis. AB - Neurofibromatosis, a common, progressive, autosomal dominant disorder, is markedly variable in its expressivity. Some authors have suggested that some contribution to neurofibromatosis's variability may be an adverse effect of a mother's neurofibromatosis on the overall severity seen in her offspring with neurofibromatosis. In the present study of 188 maternal affected, paternal affected, and sporadic von Recklinghausen neurofibromatosis cases, the maternal influence question was systematically examined. Overall severity, selected features most likely to reflect in utero maternal influence, and other common neurofibromatosis-I features were analyzed statistically. Age, racial composition, and gender of the three groups were similar. No significant differences were found (P less than or equal to .01) between maternal affected, paternal affected, and sporadic cases in terms of overall severity, probability of reaching advanced severity as a function of age, indications of possible prenatal influence (eg, congenital neurofibromas, tibial pseudarthrosis), or other neurofibromatosis features. These results demonstrate that the nature and severity of neurofibromatosis for maternal affected cases are essentially the same as for paternal affected and sporadic cases. PMID- 3103093 TI - Nonsurgical management of children with recurrent or unresectable fibromatosis. AB - At The Children's Hospital of Philadelphia, since 1971, six children 3 months to 17 years of age with fibromatosis have been treated with a combination of vincristine, actinomycin D, and cyclophosphamide (VAC). The first three patients also received radiation therapy (5,500 rads). Locally recurrent tumors developed in four of the children after previous operative removal; the other two had tumors that could not be removed initially. The tumors arose in the neck (three patients), pelvis (two patients), or foot (one patient). In the three patients treated with VAC alone, complete disappearance of tumor was confirmed at second operation in two, and greater than 75% shrinkage on CT scans occurred in the third, all at 4 to 6 months after VAC was started. In two of the three patients who received VAC plus radiation therapy, complete disappearance of tumor occurred at 13 and 16 months; the third had no response. Five of the six patients are free of recurrent fibromatosis at 1, 2, 4, and 11 years after VAC was begun; the sixth has required multiple operations during the last 6 years. We conclude that combination chemotherapy with VAC can produce regression of fibromatosis in some children with recurrent or unresectable lesions. The administration of VAC should be considered for children with fibromatosis in whom operative removal is not feasible, would prove mutilating, or is unlikely to produce long-term control of the disease. PMID- 3103094 TI - Vitamin dosages in premature infants. PMID- 3103095 TI - Chloride transport in the diluting segment of the K+ adapted frog kidney: effect of amiloride and acidosis. AB - The hypothesis was tested whether amiloride and/or an acute acid load influence Cl- transport in the diluting segment of the isolated-perfused kidney of the K+ adapted frog (rana pipiens). Transepithelial resistance (luminal cable analysis) and Cl- net flux (Cl- sensitive microelectrodes) were evaluated at various concentrations of amiloride, at high pCO2 or low HCO-3 in the kidney perfusate. Amiloride or an acute acid load increase transepithelial resistance. The resistance-change at given concentrations of amiloride is markedly enhanced under static head conditions, i.e. at low luminal NaCl concentrations. Amiloride or acidosis (high pCO2) reduce Cl- net reabsorption; combination of both potentiates this inhibitory effect. We conclude: an acute acid load acidifies the cell cytosol. This effect is aggravated dramatically after amiloride-induced inhibition of the luminal Na+/H+ exchanger. The luminal pH-sensitive K+ conductance decreases. This results in a depolarization of the cell membranes. Consequently, the peritubular electrochemical driving force for the exit step of Cl- (from cell to blood) dissipates. Therefore, Cl- net reabsorption is blunted. PMID- 3103096 TI - Correlation between apical intramembrane particles and H+ secretion rates during CO2 stimulation in turtle bladder. AB - To correlate the prevalence of rod-shaped intramembrane particles (RSP) in the apical membranes of carbonic anhydrase-rich (CA) cells and the H+ transport rate in turtle urinary bladder, we carried out morphometric studies by means of scanning and freeze-fracture electron microscopy of the alpha and beta subpopulations of CA cells. Correlations were made between the apical membrane areas of alpha cells and H+ transport rate at 0 and 5% ambient CO2. Exposure to CO2 more than doubled the planar area of the luminal surface of alpha cells and increased the degree of folding (amplification) of the apical cell membrane from 2.8 +/- 0.3 to 3.8 +/- 0.3. The actual apical membrane area of alpha cells increased from 176 mm2 to 693 mm2 per 8 cm2 epithelial area. The RSP density also appeared to be increased by about 40%. The total CO2-induced increase in RSPs in position at the luminal surface was 5 fold while the increase in H+ transport was 9-fold. We conclude that stimulation of H+ transport by CO2 involves recruitment of RSP to the apical cell membrane of alpha-type CA cells and that RSPs are associated with active H+ transport. They may represent linear arrays of transmembrane components of H+ pumps. PMID- 3103097 TI - [Reoxygenation after a single dose of 15 Gy in the EMT6/KU sarcoma]. PMID- 3103098 TI - Chromatin association and DNA binding properties of the c-fos proto-oncogene product. AB - As a first step in the analysis of the molecular function of the nuclear c-fos proto-oncogene product we have studied its subnuclear localization in serum stimulated mouse fibroblasts where it forms a non-covalent, apparently monodisperse complex with another nuclear protein, p39. The c-fos/p39 complex is almost quantitatively released from intact nuclei by DNasel or micrococcus nuclease treatment under conditions where only a minor fraction of DNA and nuclear proteins is released. In gel filtration experiments, c-fos/p39 comigrates with chromatin and seems to be associated with regions of increased DNasel accessibility. c-fos/p39 is bound to chromatin by electrostatic forces of moderate strength since greater than 90% of the complex can be eluted from nuclei at 0.4 M NaCl. In vitro, the c-fos/p39 complex in nuclear extracts binds to double- and single-stranded calf thymus DNA, suggesting that the association of c fos/p39 with chromatin is at least in part due to its interaction with DNA. In agreement with this conclusion, c-fos/p39 is released from nuclei by incubation with tRNA, presumably due to competition for binding sites. Our observations are compatible with the hypothesis that c-fos may play a role in the regulation of gene expression. PMID- 3103099 TI - Structure determination of a new fluorescent tricyclic nucleoside from archaebacterial tRNA. AB - A highly fluorescent nucleoside was detected in enzymatic digests of the extremely thermophilic archaebacterium Sulfolobus solfataricus by combined liquid chromatography-mass spectrometry (LC/MS). Following isolation, the structure was determined primarily by mass spectrometry, to be 3-(beta-D-ribofuranosyl)-4,9 dihydro-4,6,7-trimethyl-9-oxoimidazo[ 1, 2-a]purine (mimG), a new derivative of the Y (wye) nucleoside. The structural assignment was verified by comparison of the base released by acid hydrolysis with the corresponding synthetic base, using mass spectrometry, chromatography, and UV absorption and fluorescence properties. Nucleoside mimG was also detected by LC/MS in hydrolysates of the thermophiles Thermoproteus neutrophilus and Pyrodictium occultum. These results constitute the first finding of a member of the hypermodified Y family of nucleosides in archaebacteria. PMID- 3103100 TI - The terminus of Tetrahymena pyriformis mtDNA contains a tandemly repeated 31bp sequence. PMID- 3103101 TI - Structural analysis of the Drosophila rpA1 gene, a member of the eucaryotic 'A' type ribosomal protein family. AB - The expression of ribosomal protein (r-protein) genes is uniquely regulated at the translational level during early development of Drosophila. Here we report results of a detailed analysis of the r-protein rpA1 gene. A cloned DNA sequence coding for rpA1 has been identified by hybrid-selected translation and amino acid composition analysis. The rpA1 gene was localized to polytene chromosome band 53CD. The nucleotide sequence of the rpA1 gene and its cDNA have been determined. rpA1 is a single copy gene and sequence comparison between the gene and its cDNA indicates that this r-protein gene is intronless. Allelic restriction site polymorphisms outside of the gene were observed, while the coding sequence is well conserved between two Drosophila strains. The protein has unusual domains rich in Ala and charged residues. The rpA1 is homologous to the "A" family of eucaryotic acidic r-proteins which are known to play a key role in the initiation and elongation steps of protein synthesis. PMID- 3103103 TI - A model study directed towards the preparation of nucleopeptides via H phosphonate intermediates. AB - The monofunctional phosphitylating reagents bis-(N,N-diethylamino)chlorophosphine and salicylchlorophosphine have been applied for the preparation of H phosphonates of the amino acids serine, threonine and tyrosine. Experimental evidence showed that the latter reagent was less effective for the synthesis of a tyrosine H-phosphonate. The amino acids (peptide) H-phosphonates of serine or threonine proved to be suitable starting compounds for the formation of a phosphate diester bond with the 5'-OH of a d-nucleoside derivative using pivaloyl chloride as the activating reagent. PMID- 3103102 TI - Posttranscriptional regulation of c-fos mRNA expression. AB - The transient induction of c-fos mRNA and protein suggests that regulation occurs not only by transcriptional activation but also at the level of turnover of the gene product. Here we present evidence for the rapid turnover of c-fos mRNA and some of the requirements for its specific degradation. The half life of induced mature cytoplasmic c-fos mRNA is 9 min in both serum-starved and growing primary human fibroblasts and in NIH 3T3 cells. A structure present at the 3' end of the c-fos mRNA molecule is involved in its low stability since the substitution or the removal of the untranslated 3' portion prolongues the RNA life time. The rapid turnover of fos mRNA requires, in addition, continued protein synthesis. Treatment of cells with cycloheximide stabilizes c-fos mRNA. Washing out cycloheximide reestablishes the rapid turnover. Both changes occur with lag periods of less than 17 minutes. PMID- 3103104 TI - The complete nucleotide sequence of the trpC gene from Penicillium chrysogenum. PMID- 3103105 TI - Nucleotide sequence of the beta-lactamase I gene of Bacillus cereus strains 569/H and 5/B. PMID- 3103106 TI - [Effect of supplementary parenteral feeding on plasma protein levels in patients with cancer of the pharynx and esophagus treated by irradiation]. PMID- 3103107 TI - [A technic of pelvic irradiation in cervical cancer using the Neptum 10P accelerator]. PMID- 3103108 TI - [Neurofibromatosis of the skin of the head]. PMID- 3103109 TI - Potential therapeutic indications for growth hormone and growth hormone-releasing hormone in conditions other than growth retardation. AB - Growth hormone (GH) previously was available in limited supply and only for the treatment of GH-deficient children. The recent production of GH by recombinant DNA technology has provided a potential surfeit of this hormone and raises the possibility of its use in other conditions. In addition, the isolation, characterization, and synthesis of GH-releasing hormone (GRH) provides an opportunity to use this peptide in conditions in which increased circulating levels of GH are desired. Both GH and GRH have potential therapeutic uses in conditions other than growth retardation. PMID- 3103110 TI - [Standardization of the complement fixation test (CFT) in brucellosis. I. The Polish standard of anti-Brucella abortus serum]. AB - The purpose of this paper was to prepare an indigenous standard of anti-Brucella abortus serum for the complement fixation test (CFT) as a homologue of the secon International Standard of anti-Brucella abortus Serum (ISABS-II), which contains 1000 international units of complement-fixing antibodies in 1 cm3. The indigenous Standard of anti-Brucella Abortus Serum (ISABAS) was prepared in 1975. The material used was the serum of a cow infected with Br.abortus, biotype 1, under natural conditions. The cow was beheaded on the 54th day after abortion. The serum obtained was filtered through a Seitz EK filter and appropriately diluted with normal bovine serum. The preparation was lyophilized in 8500 ampules, each of which contained 1 cm3 of serum. They were filled with nitrogen before closing them. It was shown that ISABAS activity in CFT was approximate to that of ISABS II. The studies in CVL, Weybridge showed that one ampule contained 1115 international units of complement-fixing antibodies. ISABAS titres in the agglutination test (AT) and antiglobulin test (AGT) were 320+ + and 2560+ + + respectively. Reduction with 2-mercaptoethanol and separation on a column with Sephadex G-200 gel showed that anti-Brucella antibodies occurred in ISABAS mainly in IgG class. ISABAS lyophilizate is characterized by stability of CFT titre, good solubility and a low anticomplementary activity. The average weight of the lyophilizate in an ampule is 79.57 mg, standard deviation - 0.36%. ISABS may serve as the basis of antigen standardization and other elements of indigenous CFT technique in brucellosis. PMID- 3103111 TI - [Evaluation of the sensitivity of selected bacterial strains to cefuroxime]. PMID- 3103112 TI - [Effect of nitroglycerin administration on serum lysozyme level during the treatment of acute ischemic heart disease]. PMID- 3103113 TI - Kinetic evaluation of the effect of LHRH analog on prostatic cancer using transrectal ultrasonotomography. AB - The size of the prostate was measured in 11 patients with the prostatic cancer by means of transrectal ultrasonotomography after LHRH analog ([Ser(Bu)6] LHRH) treatment. Prostate volume changed parallel to serum testosterone (T) level and decreased by 17-62% compared with baseline after LHRH analog treatment for 4 months. Two different patterns were observed for the change in prostatic volume. Type A expanded transiently and then decreased gradually, while type B decreased continuously from the beginning with no expansion. After treatment for 4 months, the prostatic volume of type A was significantly less than that of type B. It is suggested that prostatic cancer showing a type A regression curve may be more sensitive to T, resulting in a better prognosis than type B. PMID- 3103114 TI - Complete response of lung metastases caused by prostatic cancer after chronic administration of a gonadotropin-releasing hormone analog, buserelin (HOE 766). AB - A stage D2 prostate cancer patient with biopsy-proven lung metastases and negative work-up for metastases is discussed. Treatment consisted of hormonal therapy in the form of chronic administration of an analog of gonadotropin releasing hormone (GnRH-A), Buserelin, with follow-up for 24 months. The complete response of the patient to GnRH-A therapy provides an interesting and unusual case in the understanding of the biological behavior of prostate cancer. PMID- 3103115 TI - Jejunostomy or gastrostomy? Why the choice is clear for the physically and mentally incapacitated. PMID- 3103116 TI - Chemical injuries to the eyes. Emergency, intermediate, and long-term care. AB - The first step in treatment of chemical injuries to the eyes is immediate, thorough, and if necessary, prolonged irrigation. Ophthalmologic consultation should be obtained early in the course of treatment, and in severe injuries an anterior chamber tap (paracentesis) may be of benefit. Topical cycloplegics and antibiotics should be administered and a "bandage" contact lens placed to protect the corneal epithelium. If the eyelid is involved, care must be taken to protect the cornea and provide a moist local environment. Long-term care of the severely injured eye is fraught with difficulties, including glaucoma and recurrent corneal ulcerations. PMID- 3103117 TI - First trimester diagnosis of Rho (D) with an immunofluorescence technique after chorionic villus sampling. AB - Double indirect immunofluorescence technique (DIIF) was applied to fetal erythrocytes from vascularized chorionic villi, obtained by chorionic villus sampling (CVS) in the first trimester of pregnancy, to determine the presence of Rhesus antigen Rh (D). PMID- 3103118 TI - A clinically effective breast cancer screening program can be cost-effective, too. AB - The logistics of complying with current American Cancer Society breast cancer screening recommendations in a large health maintenance organization, serving more than 50,000 women age 40 or older, are described. An alternative screening approach estimated to be at least as health-effective as the American Cancer Society recommendations has been developed and appears to solve the problem and is financially feasible. Cost-effectiveness depends on optimal use of mammography and health-care personnel resources. The authors show how the start-up and maintenance costs of an organized program can be offset by future cost savings resulting from reduced long-term disability in patients diagnosed at Stages 0-1 as opposed to Stages 2 and later. Careful selection of the delivery model before implementation can make a breast cancer screening program cost-effective as well as health-effective. PMID- 3103119 TI - [Bioluminescent methods of analysis in microbiology]. AB - The prospects for application of bioluminescent ATP-metry in microbiology are considered. A bioluminescent assay is proposed to analyse biomass by measuring the content of intracellular ATP by means of immobilized firefly luciferase after ATP extraction with dimethylsulfoxide. The assay can be used for plotting the growth curves of microorganisms and for determining the sensitivity of microorganisms to antibiotics. The detection limit of the assay is 700 cells per ml of the measured solution. PMID- 3103121 TI - Adaptation of Drosophila melanogaster populations to high mutation pressure: evolutionary adjustment of mutation rates. AB - Evolutionary aspects of high mutation pressure were studied in laboratory populations of Drosophila melanogaster that have irradiation histories up to 600 generations. Dose-response regressions for the x-ray induction of various types of mutation were obtained from six of these populations. The sensitivity of these irradiated populations relative to an unirradiated control population was characterized by dose reduction factors. Sensitivity decreased stepwise with the stepwise increase in irradiation levels to which the populations had been exposed every generation (0 R, 2 kR, 4 kR, 8 kR; 1 R = 0.258 mC/kg) but remained the same over hundreds of generations when the irradiation levels were constant. Resistance is controlled by single genetic factors. Additional factors evolved in subpopulations exposed to increased irradiation levels, and different factors evolved in populations that were kept separate from the beginning of their irradiation histories. Two of three factors persisted in subpopulations no longer irradiated, but one factor disappeared; this last one behaved like a transposon. Factors of relative radio-resistance are stage specific (immature oocytes) and some of them are assumed to modify or control mutation-rate genes. The resistance factors enable populations to achieve an equilibrium between the amounts of environmental mutagens and intrinsic mutation rates. PMID- 3103120 TI - Chelation of intracellular calcium blocks insulin action in the adipocyte. AB - The hypothesis that intracellular Ca2+ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca2+ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin stimulated glucose transport (IC50, 26 microM quin-2 AM) without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl2 and the Ca2+ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl2 from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation (IC50, 11 microM quin-2 AM) and the ability of insulin to inhibit cAMP-stimulated lipolysis (IC50, 78 microM quin-2 AM), without affecting their basal activities. Incubation of cells with 100 microM quin-2 or quin-2 AM had no effect on intracellular ATP concentration or the specific binding of 125I-labeled insulin to adipocytes. These findings suggest that intracellular Ca2+ is an essential component in the coupling of the insulin activated receptor complex to cellular physiological/metabolic machinery. Furthermore, differing quin-2 AM dose-response profiles suggest the presence of dual Ca2+-dependent pathways in the adipocyte. One involves insulin stimulation of glucose transport and oxidation, whereas the other involves the antilipolytic action of insulin. PMID- 3103122 TI - Allelic inclusion in a pre-B-cell line that generates immunoglobulin heavy chain genes in vitro. AB - In a pre-B-cell line that rearranges its heavy chain gene segments in vitro, we found that the rate of productive rearrangement on one allele was not influenced by the presence of heavy chain protein encoded by the other allele. This shows that allelic exclusion of heavy chain genes is not regulated at the genetic level. PMID- 3103123 TI - Nucleotide sequences of immunoglobulin epsilon genes of chimpanzee and orangutan: DNA molecular clock and hominoid evolution. AB - To determine the phylogenetic relationships among hominoids and the dates of their divergence, the complete nucleotide sequences of the constant region of the immunoglobulin epsilon-chain (C epsilon 1) genes from chimpanzee and orangutan have been determined. These sequences were compared with the human epsilon-chain constant-region sequence. A molecular clock (silent molecular clock), measured by the degree of sequence divergence at the synonymous (silent) positions of protein encoding regions, was introduced for the present study. From the comparison of nucleotide sequences of alpha1-antitrypsin and beta- and delta-globin genes between humans and Old World monkeys, the silent molecular clock was calibrated: the mean evolutionary rate of silent substitution was determined to be 1.56 X 10( 9) substitutions per site per year. Using the silent molecular clock, the mean divergence dates of chimpanzee and orangutan from the human lineage were estimated as 6.4 +/- 2.6 million years and 17.3 +/- 4.5 million years, respectively. It was also shown that the evolutionary rate of primate genes is considerably slower than those of other mammalian genes. PMID- 3103124 TI - V kappa and J kappa gene segments of A/J Ars-A antibodies: somatic recombination generates the essential arginine at the junction of the variable and joining regions. AB - The germ-line elements for the variable (V) and joining (J) regions of the kappa chains (V kappa-Ars, J kappa 1) that give rise to the productive allele for the A/J mouse light chains of Ars-A monoclonal antibodies (directed against the hapten p-azophenylarsonate) have been cloned and sequenced as well as a rearranged Ars-A light chain gene. Using the V kappa-Ars gene as a hybridization probe, we provide evidence that the V kappa 10 family is relatively small and that only one member gives rise to the productive allele in all Ars-A antibodies. An unusual feature of Ars-A light chains is that all contain an arginine at position 96, the V-J junctional position. We had shown by chain recombination that arginine-96 was essential for antigen binding. In the present study, an arginine codon was not found either at the 3' end of the V kappa-Ars gene segment or at the 5' end of J kappa 1. However, an arginine codon (CGG) can easily be generated by recombination between these two germ-line elements. Thus, we document that junctional diversity through intracodonic recombination can be crucial to the antibody binding function of the resulting molecule. PMID- 3103125 TI - The role of class I histocompatibility antigens in the regulation of T-cell activation. AB - Class I major histocompatibility antigens in humans (HLA antigens) were found to participate in the regulation of T-cell activation and proliferation induced by phytohemagglutinin. W6/32, a monomorphic antibody directed against class I HLA A,B,C antigens, significantly inhibited the phytohemagglutinin-induced cell proliferation of peripheral blood lymphocytes. Almost complete suppression of cell activation was achieved on a subfraction of peripheral blood lymphocytes enriched in Mo1+ monocyte/macrophage cells. This inhibition of cell proliferation takes place at an early stage of activation and was found to be adherent cell dependent. Removal of monocyte/macrophage type cells from peripheral blood lymphocytes completely abrogated the inhibitory influence of anti-HLA-class I antibody, and, upon adding them back, suppression reappeared. Indirect immunofluorescence demonstrated that the expression of receptors for interleukin 2 and transferrin was impaired in the presence of antibody. Although the amount of interleukin 2 synthesized by these cells was also reduced, the addition of exogenous purified interleukin 2 did not restore cell proliferation. Mitogenesis induced by the Ca2+ ionophore A23187 was similarly suppressed, but mitogenesis induced by the phorbol diester phorbol myristate acetate, which activates cells by directly stimulating protein kinase C, was not suppressed. These results are consistent with a hypothesis that HLA class I antigens regulate an early event(s) of the Ca2+-dependent pathway of activation of T lymphocytes and that this event(s) apparently occurs before protein kinase C stimulation. PMID- 3103126 TI - Prevention of tumorigenesis of oncogene-transformed rat fibroblasts with DNA site inhibitors of poly(ADP ribose) polymerase. AB - The EJ-ras gene was placed under the transcriptional control of the steroid inducible mouse mammary tumor virus promoter/enhancer and introduced into Rat-1 fibroblasts, yielding the 14C cell line. When these cells were exposed to dexamethasone in vitro, EJ-ras mRNA was induced 15- to 20-fold, the cells grew in agar, and, after injection of cells into syngenic Fischer 344 rats, they produced lethal fibrosarcomas. Inhibitors of poly(ADP ribose) polymerase, which prevent the activation of the purified enzyme by a synthetic octadeoxyribonucleotide duplex, inhibited both in vivo tumorigenicity and in vitro growth in soft agar. The enzyme inhibitor 1,2-benzopyrone, which was studied in detail, and other polymerase inhibitors had no effect on EJ-ras mRNA or p21 protein expression. Poly(ADP ribose) polymerase [NAD+:poly(adenosine diphosphate D-ribose) ADP-D ribosyltransferase, EC 2.4.2.30] was inhibited by the drug in both untreated and dexamethasone-treated cells both in vitro and in vivo to the same extent, but biological consequences of enzyme inhibition were manifest only when the cells were in the transformed tumorigenic state. PMID- 3103127 TI - Hoogsteen base pairs proximal and distal to echinomycin binding sites on DNA. AB - Forms of the DNA double helix containing non-Watson-Crick base-pairing have been discovered recently based on x-ray diffraction analysis of quinoxaline antibiotic oligonucleotide complexes. In an effort to find evidence for Hoogsteen base pairing at quinoxaline-binding sites in solution, chemical "footprinting" (differential cleavage reactivity) of echinomycin bound to DNA restriction fragments was examined. We report that purines (A greater than G) in the first and/or fourth base-pair positions of occupied echinomycin-binding sites are hyperreactive to diethyl pyrocarbonate. The correspondence of the solid-state data and the sites of diethyl pyrocarbonate hyperreactivity suggests that diethyl pyrocarbonate may be a sensitive reagent for the detection of Hoogsteen base pairing in solution. Moreover, a 12-base-pair segment of alternating A-T DNA, which is 6 base pairs away from the nearest strong echinomycin-binding site, is also hyperreactive to diethyl pyrocarbonate in the presence of echinomycin. This hyperreactive segment may be an altered form of right-handed DNA that is entirely Hoogsteen base-paired. PMID- 3103128 TI - Images of a lipid bilayer at molecular resolution by scanning tunneling microscopy. AB - The molecular structure of a fatty acid bilayer has been recorded with a scanning tunneling microscope operating in air. The molecular film, a bilayer of cadmium icosanoate (arachidate), was deposited onto a graphite substrate by the Langmuir Blodgett technique. The packing of the lipid film was found to be partially ordered. Along one axis of the triclinic unit cell the intermolecular distance varied randomly around a mean of 5.84 A with a SD of 0.24 A. Along the other axis the mean distance was 4.1 A and appeared to vary monotonically over several intermolecular distances, indicating that a superstructure of longer range may exist. The molecular density was one molecular per 19.4 A2. The surprising ability of the scanning tunneling microscope to image the individual molecular chains demonstrates that electrons from the graphite can be transferred along the molecular chains for a distance of 50 A. PMID- 3103129 TI - Gene encoding cytoskeletal proteins in Drosophila rhabdomeres. AB - The ninaC gene is one of eight nina (neither inactivation nor afterpotential) genes identified from mutations that drastically reduce the amount of rhodopsin in the compound eye of Drosophila melanogaster. The gene has been cytogenetically localized to the 27E-28B region of the second chromosome. NaDodSO4/PAGE analysis of eye proteins of flies carrying one, two, or three copies of the ninaC region shows that two eye-specific proteins of molecular weight 170,000 and 130,000 display a strong dependence on the dosage of the ninaC gene, although the dependence is evident only when the dosage is decreased and not when it is increased. All mutations in the ninaC gene studied to date have pronounced effects on these two polypeptides. These results suggest that the ninaC locus encodes these two polypeptides. Ultrastructural studies show that the polypeptides encoded by ninaC are very likely to be important components of the cytoskeletal structure of rhabdomeral microvilli. PMID- 3103130 TI - Effect of elastin peptides on ion fluxes in mononuclear cells, fibroblasts, and smooth muscle cells. AB - Elastin peptides prepared by alcoholic potassium hydroxide degradation of highly purified fibrous elastin from bovine ligamentum nuchae (kappa-elastin) were shown to act on the ion channels of human monocytes, aorta smooth muscle cells, and skin fibroblasts. In small amounts (between 0.1 and 1 microgram/ml), elastin peptides strongly increased calcium influx and inhibited calcium efflux by an apparently calmodulin-dependent mechanism. They also were shown to increase sodium influx and to decrease rubidium influx in monocyte preparations obtained from human blood. Only the ouabain-sensitive portion of rubidium influx was inhibited. The action of elastin peptides is strongly concentration-dependent; the maximal activity observed in the above reactions was less than 1 microgram/ml. These results suggest that elastin peptides may play a role in the regulation of the biological activity of mesenchymal cells, in the proximity of which they are released by the action of elastase-type enzymes. Such enzymes were demonstrated in aorta smooth muscle cells (membrane-bound serine protease) and in fibroblasts (metalloprotease). Monocytes and polymorphonuclear leukocytes were also shown to carry elastase-type enzymes. The release of peptides from elastin by elastase-type enzymes and the action of such peptides on the ion fluxes through the cell membrane may well be involved in mechanisms of the modulation of the phenotype of mesenchymal cells during aging as well as in the development of age-dependent pathologies such as arterioclerosis. PMID- 3103131 TI - Hydrocarbon formation in the reductive cleavage of hydroperoxides by cytochrome P 450. AB - Evidence is presented that cytochrome P-450 catalyzes the reductive cleavage of hydroperoxides. For example, in a reconstituted system containing rabbit liver microsomal P-450 form 2, NADPH-cytochrome P-450 reductase, and NADPH, cumyl hydroperoxide yields acetophenone and methane, but no cumyl alcohol is formed. The stoichiometry of the reaction and similar results with alpha-methylbenzyl, benzyl, and t-butyl hydroperoxides are in accord with the following general equation, in which X represents an alkyl group and R and R' are either alkyl groups or hydrogen atoms in the starting peroxide: XRR'C-OOH + NADPH + H+----XRCO + R'H + H2O + NADP+. Because 13-hydroperoxy-9,11-octadecadienoic acid yields pentane under these conditions, we propose that the known formation of alkanes and aldehydes in membrane lipid peroxidation involves reductive cleavage by P-450 to give the products predicted by the above equation. The cleavage reaction is thought to involve stepwise one-electron transfer, resulting in homolysis of the peroxide oxygen-oxygen bond and generation of an alkoxy radical, with beta scission of the latter followed by reduction of the secondary radical to the hydrocarbon. In accordance with this scheme, when the cleavage reaction with cumyl hydroperoxide was done in 2H2O, deuteromethane was formed. PMID- 3103132 TI - Poly(ADP-ribose) may signal changing metabolic conditions to the chromatin of mammalian cells. AB - In mammalian cells, NAD+ serves a dual role as a respiratory coenzyme and as a substrate for the posttranslational poly(ADP-ribose) modification of chromatin proteins, catalyzed by the nuclear enzyme poly(ADP-ribose) polymerase [NAD+ ADP ribosyltransferase, EC 2.4.2.30]. Biological evidence strongly suggests that poly(ADP-ribosyl)ation modulates chromatin functions, although the precise molecular mechanisms involved have not yet been elucidated. Here we describe conditions for the rapid uptake of exogenously supplied NAD+ by living hepatocytes in primary monolayer culture. Raising the intracellular NAD+ concentration by 70% caused a 5-fold increase of chromatin-bound poly(ADP ribose). We conclude that the constitutive level of posttranslational poly(ADP ribose) modifications of chromatin proteins in mammalian cells is related to the availability of NAD+, which varies in different physiological and pathological states. We propose that poly-(ADP-ribose) may serve a hitherto unrecognized function by signaling altered metabolic conditions to the chromatin and thus modulate its functions in tune with changing metabolic states. PMID- 3103133 TI - Antigen-receptor interaction requirement for conjugate formation and lethal-hit triggering by cytotoxic T lymphocytes can be bypassed by protein kinase C activators and Ca2+ ionophores. AB - We show that phorbol esters and Ca2+ ionophores can trigger the lysis of nonantigen-bearing target cells by cytotoxic T lymphocytes. This effect obviates the requirement for antigen-receptor-mediated recognition of the antigen; the intensity of lysis is dose and Ca2+ dependent and requires contact between cytotoxic T lymphocytes and target cells. Using a fluorescence-activated cell sorter to enumerate cytotoxic T lymphocyte-target cell conjugates, we show that phorbol esters at concentrations that triggered lysis of non-antigen-bearing target cells also increased the number of stable conjugates with these target cells. The results point to the importance of the antigen-nonspecific engagements of cytotoxic T lymphocytes in immunologic surveillance. The data also show that the linkage between the T-cell receptor and antigen is not mandatory for conjugate formation, for the strengthening of conjugates, and for lysis. PMID- 3103134 TI - Crosslinking of surface antigens causes mobilization of intracellular ionized calcium in T lymphocytes. AB - Antibodies binding to a large subset of T-cell differentiation antigens, including CD2, CD4, CD5, CD6, CD7, CD8, Tp44, and CDw18, cause an increase in the cytoplasmic calcium concentration [( Ca2+]i) after the antigens are crosslinked on the cell surface. Similar crosslinking-induced signals were seen for a subset of mouse thymocyte differentiation antigens. The various antigens on human T cells differed in the extent of crosslinking required for generating the calcium signal, as evidenced by comparisons with monoclonal versus polyclonal second-step antibody. The [Ca2+]i increase that occurs after crosslinking represents mobilization of cytoplasmic calcium since the initial component of the signal is resistant to depletion of extracellular calcium by chelation with EGTA. The [Ca2+]i increase is completely inhibited by pretreatment of cells with pertussis toxin, indicating that a substrate for pertussis toxin regulates the signal transduction. Crosslinking of antigens other than the CD3/T-cell receptor complex did not result in T-cell proliferation. Crosslinking of CD2 and Tp44, but not other antigens, resulted in expression of functional interleukin 2 receptors. Comparisons of three different anti-CD3 antibodies showed that a second calcium signal was generated by crosslinking, even when the anti-CD3 antibodies were used at optimal concentrations. PMID- 3103135 TI - Pharmacokinetics of aspirin and salicylate in relation to inhibition of arachidonate cyclooxygenase and antiinflammatory activity. AB - Among the nonsteroid antiinflammatory drugs there is generally a close correlation between the potency of their inhibition of arachidonate cyclooxygenase, and thus prostaglandin production, and their antiinflammatory activity. One anomaly in this generalization is that whereas aspirin and salicylate are equipotent as antiinflammatory agents, salicylate is less active than aspirin in inhibiting prostaglandin production in vitro. Using rats, we have now measured the concentrations of aspirin and salicylate in plasma and in inflammatory exudates after their oral administration and determined their effects on thromboxane B2 production in clotting blood and prostaglandin (PG) E2 concentrations in the exudates. We have also investigated the effects of both drugs, at concentrations achieved in the exudates, on PGE2 production by nonproliferative explants of acutely inflamed tissues. Aspirin is rapidly metabolized, resulting in peak concentrations of salicylate in the plasma and exudate that exceeded peak concentrations of aspirin by 30- to 50-fold. Furthermore, concentrations of aspirin rapidly declined, whereas high concentrations of salicylate persisted in the plasma and in the exudate for up to 6 hr after a single administration of aspirin. Both drugs reduced PGE2 concentrations in inflammatory exudates by 50-70%, but aspirin was considerably more potent than salicylate in inhibiting thromboxane B2 production in clotting blood. The concentration of salicylate found in inflammatory exudates 6 hr after the administration of aspirin was sufficient to reduce PGE2 production in explants by more than 50%. We conclude that the antiinflammatory action of both drugs depends on the inhibition of PGE2 synthesis by salicylate. PMID- 3103136 TI - The early involvement of pulmonary prostaglandins in hyperoxic lung injury. AB - To further study the role of arachidonic acid metabolites in the development of hyperoxic lung injury and the function of PMNs and/or alveolar macrophages in facilitating this role, we exposed adult rabbits to greater than 95% O2 or air for 24, 40, 48, or 65 hours. At the end of each study, bronchoalveolar lavage [BAL] of the left lung was performed, and the right lung was inflated and fixed for light and electron microscopy. PGE2, 6-keto-PGF1 alpha and thromboxane B2 were measured by RIA in arterial and venous plasma at the beginning and end of each study and in BAL fluid obtained at sacrifice. Production of these three PGs by BAL cells placed in cell culture was also measured. Significant hyperoxic lung injury did not develop until 65 hours, as evidenced by significant increase in BAL total protein and percent PMNs, and by morphologic findings. At 40 hours, however, BAL fluid PGE2 and 6-keto-PGF1 alpha increased and BAL cell production of all 3 PGs was significantly increased (p less than .05). In summary, the early PG increases observed in these studies may directly contribute to the development of hyperoxic lung injury or, rather, may be representative of a generalized increase in all arachidonic acid metabolites, including the lipoxygenase pathway. The increase in BAL cell PG production and increased PG concentrations in BAL fluid prior to any increase in BAL PMNs suggest that the AM may be the source of the early arachidonic acid metabolite increase in response to hyperoxia. PMID- 3103137 TI - Isolation and effects of some ginger components of platelet aggregation and eicosanoid biosynthesis. AB - Aqueous ginger extract was extracted in three organic solvents viz., n-hexane, chloroform and ethyl acetate with increasing polarity. The extracted materials from these solvents reduced platelet thromboxane formation from exogenous arachidonate (AA) and also inhibited platelet aggregation induced by AA, epinephrine, ADP and collagen; in this respect they were most effective against AA-induced aggregation. The extracted material in n-hexane was further resolved by thin-layer chromatography into various fractions some of which were effective in inhibiting platelet thromboxane formation and platelet aggregation. Aqueous ginger extract reduced the formation of TxB2 from AA-labelled platelets without showing effects on platelet phospholipase activity. Thromboxane formation in labelled platelets on activation with calcium ionophore A23187 was reduced by ginger components, isolated from two TLC bands, in a dose-dependent manner (10 100 ug/500 ml). At the higher dose lipoxygenase products were also reduced. Interestingly the incorporation of AA into platelet phospholipids increased in platelets treated with aqueous ginger extract. PMID- 3103138 TI - The effect of BW 755C and nordihydroguaiaretic acid in the rat isolated perfused mesenteric vasculature. AB - The suitability of two lipoxygenase inhibitors to study the putative effects of leukotrienes (LTs) in rat isolated perfused mesentery has been assessed. Both the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the dual lipoxygenase and cyclo-oxygenase inhibitor BW 755C depressed vasoconstrictor responses to NA, an effect characteristic of cyclo-oxygenase inhibitors on this tissue. However, depression of responses to NA by NDGA was non-selective since it depressed responses to calcium over the same concentration range. BW 755C possessed some selectivity for inhibition of responses to NA compared to calcium. The difference in relative selectivities between the two inhibitors was confirmed using prostaglandin E2 (PGE2), which reversed responses to NA depressed by BW 755C to a greater extent than those depressed by NDGA. LTC4 and LTD4 neither caused vasoconstriction nor reversed responses to NA depressed by BW 755C. Since NDGA in particular caused depression in this tissue, results using this drug to investigate the possible role of LTs in other blood vessels should be treated with caution. PMID- 3103139 TI - Effects of variable linoleate intake on aortic PGI2-like activity and fatty acid composition: difference between rat and marmoset (Callithrix jacchus). AB - Two animal species, the laboratory rat and a non-human primate (the common marmoset) were compared with respect to the influence of dietary lipid supplementation on both fatty acid composition and prostanoid synthetic capacity of aorta. Standard chow (REF. diet) was supplemented (12% w/w) with either sheep fat (SF) or sunflower seed oil (SSO). Differences were apparent in the aortic phospholipid fatty acids from both animal models, as a result of the diet, although the type and the extent of changes displayed a considerable species variation. For example, after the SSO diet, the proportion of linoleic acid in rat aorta displayed only a modest increase whilst in marmosets it was doubled. No change was apparent in the proportion of arachidonic acid in rats, whereas the marmosets showed a reduction (P less than 0.05) with both lipid supplements. Rats fed the SF diet showed a considerable increase in aortic PGI2-like activity compared to REF. And SSO supplemented groups. In contrast, no dietary induced changes were observed in the aorta from marmosets despite compositional changes. The results indicate no direct association between the synthesis of PGI2-like activity and membrane lipids and demonstrate the need for careful selection of the proper animal model, particularly in nutritionally orientated experiments. PMID- 3103140 TI - [Tuberculostatic action of piperidinoethyl esters of alkoxyphenylcarbamide acid in vitro]. PMID- 3103141 TI - The permeability of aortic endothelium to 125I-BSA in hyperlipidemic hamster. Effect of histamine and serotonin. AB - The aortic permeability to 125I-bovine serum albumin (BSA) and the effect of histamine and serotonin were investigated in hamsters with diet-induced hyperlipidemia. Animals, fed a cholesterol- and butter-rich diet for five weeks, were sacrificed weekly and the level of serum cholesterol, the aortic permeability, and the morphologic aspect of the vessel wall, were analysed. During this interval, the cholesterolemia increased four-fold, and a progressive lipid accumulation in the intima was recorded. The permeability of the aortic wall was assessed by injecting 125I-BSA into the circulation and detecting the radioactivity in the aortic wall. The effect of the two vasoactive amines was determined by injecting histamine or serotonin concomitantly with the 125I-BSA. The results indicate that during the early stages of experimental hyperlipidemia in hamster, the aortic wall shows an increased permeability to albumin. The process is markedly augmented by histamine and serotonin, predominantly in the abdominal aorta. PMID- 3103142 TI - Experimental model for the quantitative estimation of transendothelial transport in vitro; a two-compartment system. AB - A two-compartment system was set up for the measurement of macromolecules, particles and water transfer through the monolayers of cultured endothelial cells. Experimental parameters like differential hydrostatic and osmotic pressures (delta P and delta pi, respectively) concentration gradients, temperature could be controlled. The experiments were carried out, on a cellular line of bovine aortic endothelium produced in our laboratory. Morphological and immunological investigations attested the differentiation of these cells grown on a porous support membrane separating the two compartments. The system allowed morphologic check up on the continuity of endothelial monolayer and ultrastructural studies. Hydraulic conductivity determined for endothelial monolayers was 6.86 +/- 0.85 cm. sec-1 X cm H2O-1 X 10(-7) at delta P = 10 mm Hg and 8.23 +/- 0.80 cm. sec-1 X cm H2O-1 X 10(-7) at delta P = 30 mm Hg, which proves an adequate functional integrity. Investigations using successive radioactive pulses on the same culture were possible without notable residual radioactivity between pulses. PMID- 3103143 TI - [Cardiodynamic changes produced by physical effort performed in a hyperthermic environment]. PMID- 3103144 TI - [Thyroid hormones in chronic hepatopathies]. PMID- 3103145 TI - Bioelectric and mechanic aspects in rat small intestine muscle. PMID- 3103146 TI - [The significance of abnormal Q waves]. PMID- 3103147 TI - Atrio-ventricular conduction disturbances occurring after strenuous physical effort. AB - Two young patients with a-v conduction disturbances occurring in relation with strenuous physical effort are presented. The possible mechanism may be an excessive vagal tone. PMID- 3103148 TI - Noradrenaline and the context-dependent extinction effect. AB - Three experiments were performed to examine the effects of noradrenaline (NA) depletion upon the context-dependent extinction effects in conditioned taste aversion learning. Three different methods were used to deplete NA: lesions of the dorsal noradrenergic bundle (DNAB) with 6-hydroxydopamine (6-OHDA), lesions induced by neonatal treatment with 6-OHDA and lesions induced by systemic administration with the NA neurotoxin, N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine (DSP4). In each experiment, novel saccharin was presented in novel noisy bottle followed by lithium chloride. Later, during the extinction phase, half the control and half the NA depleted rats received saccharin in noisy bottles while the other half received saccharin in silent bottles. In the control condition, the rats that received saccharin in the noisy bottles (same context as conditioning) showed considerably more aversion than those that received saccharin in the silent bottles (different context to conditioning); NA depletion attenuated this effect. Reinstatement of the conditioning context (noisy bottle) resulted in a stronger aversion in the case where the different context (silent bottle) was present during extinction; this effect was attenuated in the NA depletion condition. These findings maintain a role for noradrenaline in compound conditioning tasks. PMID- 3103149 TI - Cardiovascular effects of central 6-OHDA treatment: a comparison of indirect and direct measurements. AB - The effect of intracerebro-ventricular treatment with 6-hydroxydopamine on blood pressure and heart rate was studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto controls (WKY). When measured with the indirect tail cuff method, the development of hypertension was found to be markedly inhibited in 6-OHDA treated SHR, while blood pressure was slightly lower in treated WKY. Heart rate was lower in both strains, although the greatest effect was found in SHR. In contrast, direct measurement via an arterial cannula indicated significantly lower blood pressure in 6-OHDA treated SHR only. Heart rate was by this method found to be not different between the SHR groups, but was increased in treated WKY. These results indicate that the mild stress of indirect blood pressure determinations has a marked influence on the results found. PMID- 3103150 TI - Motivational versus motor impairment after haloperidol injection or 6-OHDA lesions in the ventral tegmental area or substantia nigra in rats. AB - The effects of blockade of dopaminergic receptors as well as the lesions of dopaminergic neurons on the behaviour of rats in "motivational" and "motor" tests were examined. Both systemic injection of haloperidol and 6-OHDA lesions in the ventral tegmental area (VTA) or substantia nigra, pars compacta (SN/pC) induced a decrease in the number of wins made by thirsty animals fighting for water in a water competition test. The rats with lesions in the VTA became insensitive to motivational thirst stimuli. The reaction of rats lesioned in the SN/pC was still dependent on the level of thirst. Both groups did not differ from controls in the amount of water intake. In the rotating rod test the animals with destroyed nigrostriatal system showed a substantial motor impairment, while destruction of the mesolimbic system had no effect in that test. The role of dopaminergic systems in terms of their involvement in the control of motivational arousal and motor performance has been discussed. PMID- 3103151 TI - Platelet [3H]imipramine binding in autism and schizophrenia. AB - [3H]Imipramine binding to platelet membranes was evaluated in ten autistics, eight schizophrenics and seven normal controls. The schizophrenics and eight out of the ten autistics were maintained on chronic neuroleptic treatment. Diagnosis of autism and schizophrenia was established according to the DSM-III criteria. No significant difference in the maximal binding capacity of [3H]imipramine (Bmax) and Kd values could be found among the three groups. It seems that the imipramine binding site is intact both in autism and schizophrenia. PMID- 3103152 TI - The negative symptoms of schizophrenia and the monoamine oxidase inhibitors. AB - Thirty chronic ambulatory schizophrenic patients whose main psychopathology was characterized by the persistence of negative symptoms, such as emotional withdrawal, depressed mood, motor retardation and blunted affect were included in this project in order to evaluate the therapeutic efficacy of tranylcypromine plus chlorpromazine therapy. The results show that tranylcypromine when added to the usual dose of chlorpromazine, in many instances, induces a definite improvement in these patients' clinical condition, that such treatment is safe and it may be also useful in preventing the occurrence of extra-pyramidal symptoms. PMID- 3103153 TI - Selective effect of lithium on cognitive performance in man. AB - The effects of lithium on psychomotor performance were examined in six healthy male volunteers (aged 26-31 years) and compared with those of a similar control population. Three computerised psychomotor tests (serial reaction time, semantic reasoning and syntatic reasoning) were administered before lithium, after 5 and 22 days of lithium carbonate (800 mg/d) and 4 days and 1 month after stopping the lithium. The only significant effect was an impairment of semantic reasoning during the chronic (22 day) test. This suggests a selective effect of lithium on associative mental tasks and may explain the subjects' experience of slowing in recall of object names whilst taking lithium. PMID- 3103154 TI - Effects of fixed-interval duration on the development of tolerance to decreased responding by l-nantradol. AB - Key pecking of pigeons was maintained under a chained schedule in which the first response after 2 h (fixed interval) was followed by the opportunity to obtain food after sequences of 30 responses (fixed ratio), and animals received acute injections of l-nantradol (0.001-0.1 mg/kg). Smallest doses were ineffective; largest doses decreased all responding; and intermediate doses decreased fixed interval, but not fixed-ratio, responding. When animals subsequently received daily administration of 0.1 mg/kg l-nantradol prior to experimental sessions, initially decreased fixed-interval responding did not recover during 21 sessions of l-nantradol administration, whereas fixed-ratio responding was demonstrated on several occasions by automatic advancement to the fixed-ratio component. When the schedule was changed so that the same total amount of food was available after ten shorter fixed intervals, fixed-interval responding resumed within a single session, and when the schedule was changed back so that all food was available only after 2 h had elapsed, fixed-interval responding diminished within a few sessions and virtually no responding occurred for 21 additional sessions. The behavioral effects of chronic l-nantradol depended on both the schedule and the parameter of reinforcement. PMID- 3103155 TI - Supersensitivity and clozapine withdrawal. PMID- 3103156 TI - Effects of diazepam on cognitive processes in normal subjects. AB - The effects of 10 mg orally-administered diazepam on various aspects of cognition were examined in ten male subjects. Diazepam produced a subjective sense of cognitive impairment and impaired auditory vigilence, immediate recognition of twice presented words, and context-dependent free recall. There was a trend for a significant proportion of subjects to show impairment in delayed recognition of twice-presented words. There was no impairment of context-independent semantic memory, or of subjects' ability to judge how well they had performed on the free recall task. In fact, subjects' subjective sense of cognitive impairment was correlated with their performance on context-dependent memory tasks. PMID- 3103157 TI - Rebound hyperthermia follows ethanol-induced hypothermia in rats. AB - We have recently described a telemetry/microcomputer system to monitor core temperatures in rats. We implant a miniature transmitter (Mini-mitter) into the peritoneal cavity of the rat, allowing us to obtain temperatures around the clock without handling the animals or disturbing the light-dark cycle. In the present study we describe the temperature effects of ethanol doses ranging from 2 to 6 g/kg. Baseline temperatures were collected for 2 days before drug was administered. Subsequent computer analysis then allowed us to compare experimental results in each animal with its own baseline temperature to allow for individual and circadian temperature differences. In preliminary studies we observed the well-known dose-dependent hypothermic effect of ethanol. However, by observing animals continually over 4 days we also observed a period of rebound hyperthermia beginning at about the time of complete ethanol elimination and persisting for several days. During this period daytime temperatures remained at the normally high night-time level. This may be evidence of a mild abstinence syndrome, or alternatively, may be due to a disruption of the normal circadian temperature rhythm. PMID- 3103158 TI - Acute autonomic nervous system effects of caffeine in prepubertal boys. AB - The effects of caffeine on autonomic activity were tested in 19 normal prepubertal boys. Subjects received placebo, 3 mg/kg, and 10 mg/kg caffeine in a random order (double blind) before three test sessions 48 h apart. Skin conductance (SC), heart rate (HR), and skin temperature (ST) were recorded during a rest period, a series of nonsignal tones, and a simple reaction time (RT) task. Caffeine increased the frequency of both spontaneous and elicited SC responses (SCR) under all conditions. Resting SC base level (SCL) was increased, and shorter SCR half recovery time also occurred in some periods. In contrast, caffeine decreased HR and motor activity at 3 mg/kg. Evidence of improved attention on caffeine was also obtained. The physiological effects are partially similar to the effects seen in clinical anxiety states, and they are also consistent with the physiological concomitants of good sustained attention. The profile of effects did not resemble those of dextroamphetamine in a similar population. PMID- 3103159 TI - A comparison of testing procedures on the discriminative morphine stimulus. AB - The study investigated the effects of reinforcement and non-reinforcement during test sessions, and the effects of duration of generalization test sessions on the generalization of a morphine-induced discriminative stimulus. Rats were trained to discriminate 3 mg/kg morphine from saline in a two-lever drug discrimination task and were then tested for generalization of 0, 1, 2, 3, 4, and 5 mg/kg morphine with the training drug under both reinforced and non-reinforced contingencies during 4-min test periods. The percentage of drug-appropriate responses and response rates were recorded for the first 2 min and the second 2 min of each test session. A higher proportion of drug-appropriate responding occurred with an intermediate dose of morphine when reinforcement was available during test sessions. The frequency of responding was higher during the last 2 min than during the first 2 min of reinforced test sessions. The changes in response rate observed between the first 2 min and the last 2 min of the test sessions also depended on the reinforcement contingency available and the dose of morphine administered presession. The testing parameters thus altered the degree of generalization and the shape of the generalization curve of the morphine discrimination. PMID- 3103160 TI - Discriminative stimulus effects of a low dose of apomorphine in the rat. AB - The discriminative stimulus (DS) effect of apomorphine was investigated in rats trained in a two-lever, food-reinforcement procedure. Rats were given subcutaneous injections of saline or 0.1 mg/kg apomorphine HCl, 15 min before training sessions. The training dose of apomorphine was chosen to activate dopamine autoreceptors selectively. Stimulus generalization studies demonstrated that the DS effects generalized completely to other direct-acting dopaminergic agonists such as N-n-propylnorapomorphine (NPNA), pergolide, lergotrile, and bromocriptine. The indirect-acting dopamine agonists, (+)amphetamine, cocaine, and methylphenidate produced predominantly saline-appropriate lever responses. The DS effect of apomorphine at the training dose was incompletely antagonized by haloperidol or metoclopramide. The dopaminergic antagonists tested, however, also partially generalized to apomorphine. Both enantiomers of 3-(3-hydroxyphenyl)-N-n propylpiperidine (3-PPP) produced apomorphine-appropriate lever choice with the ( ) enantiomer being slightly more potent. The discriminative property of this (0.1 mg/kg) dose of apomorphine has characteristics consistent with selective dopamine autoreceptor activation. PMID- 3103161 TI - Neuropharmacological reassessment of the discriminative stimulus properties of d lysergic acid diethylamide (LSD). AB - The neuropharmacological mechanisms underlying the behavioral effects of d lysergic acid diethylamide (LSD) were assessed by comparing the discriminative stimulus properties of LSD with those of agonists and antagonists that act selectively at putative serotonin (5-hydroxytryptamine; 5-HT) receptor subtypes (5-HT1 and 5-HT2). Male Sprague-Dawley rats (N = 23) were trained to discriminate LSD (0.08 mg/kg) from saline and given substitution tests with the following agents: 8-hydroxy-2(di-n-propyl-amino) tetralin (8-OHDPAT; 0.02-0.64 mg/kg), Ru 24969 (0.2-3.2 mg/kg), m-chlorophenylpiperazine (MCPP; 0.1-1.6 mg/kg), 1-(m trifluoromethylphenyl)piperazine (TFMPP; 0.1-1.6 mg/kg), and quipazine (0.2-3.2 mg/kg). Only quipazine mimicked LSD. In combination tests, BC 105 (0.2-3.2 mg/kg), 2-bromolysergic acid diethylamide (BOL; 0.1-1.6 mg/kg), Ly 53857 (0.4-3.2 mg/kg), metergoline (0.05-0.8 mg/kg), ketanserin (0.2-3.2 mg/kg), and pipenperone (0.0025-0.08 mg/kg), all of which act as 5-HT2 antagonists, blocked the LSD cue; only spiperone (0.02-0.32 mg/kg) was without effect. Although commonalities may exist among "5-HT agonists", the present results demonstrate that such "agonists" are not identical. Since putative 5-HT1 agonists do not mimic LSD and the LSD cue is potently blocked by 5-HT2 antagonists, it appears that 5-HT2 neuronal systems are of greater importance than 5-HT1 systems in mediating the discriminative stimulus and, perhaps, other effects of LSD. PMID- 3103162 TI - Chlordiazepoxide facilitates erections and inhibits seminal emission in rats. AB - Two experiments have been conducted to clarify the effects of the benzodiazepine chlordiazepoxide (CDP) on the different components of male rat sexual behavior. In the first experiment the effects on penile erectile reflexes (PR) of two doses (10 and 30 mg/kg, IP) of CDP were compared with those of vehicle, no-treatment and baseline pre-test in a repeated measures design. In the second experiment the different components of male sexual behavior - PR, mating behavior and spontaneous seminal emission SSE) - were extensively studied after vehicle, 3 and 30 mg/kg CDP treatments. CDP was found to increase significantly the percentage of rats showing penile reflexes, enhance the number of erections per test and shorten the latency to onset of reflexes. It lowered the percentage of animals displaying seminal emission during the PR test. In the mating behavior test, CDP abolished copulatory (and other) behavior at 30 mg/kg. It decreased the number of animals achieving ejaculation at the subataxic 3 mg/kg dose level. In the SSE 3 day test, CDP significantly reduced the weight and the number of plugs of seminal material emitted by the CDP-injected animals. The possible involvement of the serotonergic system in determining the dose-dependent increase in erections and decrease in seminal emission following CDP treatments is discussed. Clinical implications are also briefly considered. PMID- 3103163 TI - Senile dementia of the Alzheimer type treated with aniracetam: a new nootropic agent. AB - Forty-four patients with senile dementia of the Alzheimer type were randomly allocated into double-blind treatment with either aniracetam (RO 13-5057) 1 g or placebo daily for 3 months. Neurological examinations were made before and after treatment and psychometric tests were performed before and after 1 month's and after 3 month's treatment. Treatment was interrupted due to occurrence of confusion in four cases in the aniracetam group and in one case in the placebo group. During treatment, an improvement was seen in several cognitive tests, especially those associated with memory, but this improvement occurred in the placebo as well as in the aniracetam-treated group. In clinical evaluation no difference was seen in efficacy between the two treatment groups. PMID- 3103164 TI - Amenorrhea and predictors for remenorrhea in anorexia nervosa: a psychoendocrinological study in inpatients. AB - 34 consecutively admitted anorexia nervosa inpatients were studied for variables relevant for 'early' vs. 'late' amenorrhea and for probable remenorrhea after therapy. The subsample reporting 'early' amenorrhea, i.e. preceding weight loss (n = 11), was characterized by less 'anorexia-specific' psychological traits and more weight loss before admission and a more marked (= pathological) FSH responsiveness to GnRH stimulation. Hence--contrary to our expectation--'early' amenorrhea seems to be a 'nonpsychogenic' phenomenon. Analysis according to FSH hyperresponsiveness yielded no additional information. Studying LH changes during therapy we found that a nonrise in basal LH secretion is associated with a type of anorexia characterized by early onset and a less severe but protracted course before admission, which then proves also more recalcitrant to therapy. The subsample which attained LH fluctuation before discharge showed a clear reduction of 'weight phobia' and a higher weight both on admission and before discharge. PMID- 3103165 TI - Ultrasonic radiation induced lipid peroxidation in liposomal membrane. AB - Ultrasonic radiation produced a dose dependent linear increase in lipid peroxidation (MDA formation) in the liposomal membrane. The yield of MDA was significantly inhibited by butylated hydroxytoluene (BHT), the antioxidant, sodium formate, the OH. radical scavenger, and EDTA, the metal ion chelator. Ascorbic acid at low concentration increased the ultrasonic induced MDA formation while high concentrations inhibited lipid peroxidation. A mechanism of ultrasound induced lipid peroxidation is suggested. PMID- 3103166 TI - [Role of protein poly(ADP-ribosylation) in the radiosensitivity of thymus lymphocytes]. AB - The inhibitors of poly(ADP-ribose) polymerase did not exert a radiomodifying effect on thymocytes. The inhibitors did not also influence single-strand breaks repair in DNA of nucleoids of irradiated cells. The participation of poly(ADP ribosylation) system in increasing the availability of thymocyte DNA damages for repair enzymes was hardly probable since benzamide in these cells did not influence the level of spontaneous genome lesions recognized by endonucleases. A possible role of protein poly(ADP-ribosylation) in thymocyte DNA repair is discussed. PMID- 3103167 TI - [Alimentary, metabolic and toxic osteopathies in adults]. AB - Skeletal changes in deficient or badly balanced nutrition (alimentary osteopathies) and osseous changes accompanying chronic disease of internal organs and metabolic disorders (metabolic osteopathies) are discussed. Basically, the classical generalised skeletal changes such as osteoporosis, osteomalacia, fibroosteoclacia and sclerosis of the bone can occur in their pure form or as a combination of two ore more of these disorders. Finally the exogenic toxic osteopathies are discussed, nowadays fluorosis being the most important. Other external factors may be drugs such as methotrexate and antiepileptic medications. PMID- 3103168 TI - [Special radiology of the hand in renal osteopathy]. AB - The different radiographical abnormalities of the hand with renal osteodystrophy are demonstrated. The soft tissue immersion low-energy X-ray technique allows early detection of macrostructural changes of spongy and compact bone, irregularities of the cortex, defects and pseudocysts, osteosclerosis as well as calcifications in the soft tissue and arterio sclerosis of patients with chronic renal failure. Possible erroneous interpretations will be discussed. PMID- 3103169 TI - Effects of 1 gram oral or intravenous aspirin on urinary excretion of thromboxane B2 and 6-keto-PGF1 alpha in healthy subjects. AB - Aspirin inhibits cyclo-oxygenase, thus preventing prostanoids formation. After oral administration aspirin is hydrolysed to inactive salicylate partly within the gastrointestinal tract, partly during first pass in the liver, partly in the circulation by plasma esterases. Intravenous aspirin, in contrast, mainly undergoes plasma esterase-catalysed deacetylation. Six healthy male subjects were given 1 g aspirin orally and intravenously two weeks apart according to a cross over randomized design. Whereas serum TxB2 generation reflecting platelet cyclo oxygenase activity was suppressed by aspirin by both routes, urinary excretion of TxB2 and 6-keto-PGF1 alpha was not affected by oral aspirin, but was partially though significantly reduced by the i.v. drug. Drug disposition seems therefore to be essential in determining the "biochemical selectivity" of aspirin as related to platelet and renal prostanoids generation. PMID- 3103170 TI - Differential effects of aspirin and dexamethasone on phospholipase A2 and C activities and arachidonic acid release from endothelial cells in response to bradykinin and leukotriene D4. AB - The CPAE bovine endothelial cell line may be stimulated to produce eicosanoids. Leukotriene D4 increased the release of arachidonic acid primarily by activating phospholipase A2 while bradykinin activated the phospholipase C pathway. Cells pretreated with dexamethasone, a phospholipase A2 inhibitor, no longer responded to stimulation by LTD4 but did release arachidonic acid when treated with bradykinin. Aspirin blocked bradykinin-stimulated production of arachidonic acid but left the response to LTD4 unaffected. We conclude that these cells produce eicosanoids by activation of both PLA2 and PLC, and that the two different methods of arachidonic acid release can be distinguished by using the common anti inflammatory drugs aspirin and dexamethasone. PMID- 3103171 TI - Stimulation of arachidonic acid metabolism: differences in potencies of recombinant human interleukin-1 alpha and interleukin-1 beta on two cell types. AB - Recombinant human interleukin-l (rIL-1) alpha and beta, which have 26% homology in their amino acid sequence, stimulated arachidonic acid metabolism by squirrel monkey smooth muscle cells and rat liver cells; their relative effectiveness, however, varied with the two cells. Recombinant IL-1 alpha was 3 times more effective than rIL-1 beta at stimulating arachidonic acid metabolism by the primate smooth muscle cells. Recombinant IL-1 alpha was 3 times less effective than rIL-1 beta when measured by their capacity to synergistically stimulate arachidonic acid metabolism of rat liver cells in the presence of palytoxin and anti-diuretic hormone (ADH). The rIL-1 alpha and rIL-1 beta also stimulated the release of radiolabelled arachidonic acid from the smooth muscle cells prelabelled with [3H]arachidonic acid. The two recombinant IL-1s have different heat stabilities, again when measured by their capacity to stimulate arachidonic acid metabolism; IL-1 alpha was more heat stable than IL-1 beta. PMID- 3103173 TI - Cyclooxygenase and lipoxygenase-like activity in Drosophila melanogaster. AB - To determine the possible activity of cyclooxygenase and lipoxygenase like enzymes in Drosophila melanogaster, we have investigated whether fly homogenates can biosynthesize prostaglandins and HETEs. Incubation of fly extracts with AA yields a mixture of 15- 12- 9- and 8-HETE as detected by selected ion monitoring GC-MS. Also the combination of HPLC-RIA using a PGE antibody shows the presence of endogenous PGE2 immunoreactivity in the extracts (405 pg/g in males and 165 pg/g in females). We have also detected the presence of lipoxygenase like immunoreactivity in the reproductive male system by using immunocytochemical techniques in whole body sections of the fly as well as reactivity in the digestive system of both males and females. Finally, we have not been able to detect endogenous AA in the fly by GC-MS methods. However, estimates by GC-MS of the total body fatty acids indicate substantial amounts of potential AA precursors. PMID- 3103172 TI - Salicylates inhibit PAF-acether-induced rat paw oedema when cyclooxygenase inhibitors are ineffective. AB - The cyclooxygenase inhibitors indomethacin, piroxicam, ibuprofen, naproxen and flurbiprofen failed to block rat paw oedema induced by PAF-acether, whereas aspirin and sodium salicylate were effective. Two mixed cyclooxygenase and lipoxygenase inhibitors NDGA, BW 755C and dexamethasone reduced oedema in a dose dependently. The selective PAF-acether antagonist, BN 52021, was effective against PAF-acether at 5 - 20 mg/kg. The lipoxygenase derivates may be involved in paw oedema induced by PAF-acether in the rat and the inhibition produced by aspirin and by sodium salicylate should involve mechanisms other than the cyclooxygenase pathway. PMID- 3103175 TI - [Contribution of the stereo-EEG to the definition of an epileptic focus]. AB - For epilepsy, surgical success rates rely on the validity of the spatial definition of the epileptogenic focus. Clinical seizure characteristics and interictal and ictal EEG patterns have been the traditional means of localization. Electrocorticography and stereo-electroencephalography are sometimes used. With stereo-EEG, the topographic determination of an epileptogenic zone depends above all on the study of the anatomo-electro-clinical correlations evidenced during the seizures themselves. Interictal abnormalities, infra-clinical discharges, stimulations also help to evaluate the topography of the focus. Because surgical success is increased neither with stereo-EEG nor with EEG, the procedure remains controversial. But stereo-EEG allows the selection of 36% more patients for surgery by defining otherwise unidentifiable single epileptogenic foci (Spencer). Furthermore, the use of stereo-EEG in seizure disorders of extra-temporal origin is a real diagnostic benefit. PMID- 3103174 TI - [Peridural anesthesia with bupivacaine-CO2 and bupivacaine-HCl. A comparative study]. AB - Carbonated bupivacaine and bupivacaine hydrochloride were used for epidural anaesthesia in patients undergoing surgery of the lower extremities. Thirty patients received 20 ml 0.5% bupivacaine hydrochloride and 32 patients 20 ml 0.42% carbonated bupivacaine. Carbonated bupivacaine had a more rapid onset of action and spread of both sensory and motor blockade than its hydrochloride salt. The differences were statistically significant. PMID- 3103176 TI - [Benign epileptic infantile spasms]. AB - Among 100 infants with infantile spasms studied before treatment, 14 had idiopathic spasms with a favourable outcome. They had a normal development, including reaching for objects before the age of 5 months and moderate regression without loss of eye following. Although it was hysarhythmic, the EEG tracing showed identifiable basic activity and sleep spindles; there was no slow waves focus even after diazepam administration and the spasms were "independent" even during a cluster. This type of infantile spasms seems to be a particular type of non-lesional epilepsy. It contrasts with idiopathic spasms of unfavourable outcome that apparently result from a preexisting and overlooked focal lesion responsible of later cognitive troubles. PMID- 3103177 TI - [Epilepsy with continuous discharges during slow-wave sleep. Treatment with clobazam]. AB - The authors describe the case of a 12 years old boy suffering from an epilepsy with complex partial seizures evolving to a syndrome of epilepsy with continuous spikes-waves during sleep. A dramatic improvement follows clobazam introduction in the treatment. The originality of this case report and the possible mechanism of action of clobazam are discussed. PMID- 3103178 TI - [Electroencephalographic study of 40 patients with subacute sclerosing panencephalitis]. AB - Among viral diseases, subacute sclerosing panencephalitis is one of the most frequent in Iran (more than 300 cases in two neurological centers and for the last ten years). This paper is devoted to an electroencephalographic study of 40 patients: visual analysis of EEG rhythms (frequency, amplitude, lability, morphology), effects of activation methods, description of pathological EEG patterns (periodic paroxysmal complexes in 38 cases; slow or fast spikes, polyspikes and bifrontal or diffuse spikewaves in 9 cases; localized comitial abnormal patterns in 5 cases; bifrontal delta rhythm in 13 cases). From this description, we suggest an hypothesis of a diffuse localisation at the origin of periodic paroxysmal patterns: the periodic discharge of immune complexes from cerebral tissue into the cerebral circulation would constitute a synchronizing system which periodically modifies the blood-brain barrier permeability. PMID- 3103180 TI - Effect of hypocalcaemia on blood flow distribution in sheep. AB - Cardiac output, the proportion of blood passing through arteriovenous shunts and blood flow distribution to various organs were measured and compared in five normocalcaemic and five hypocalcaemic sheep using radioactive microspheres. Hypocalcaemia was induced by infusing sodium EDTA solution intravenously for two hours. There was evidence that microspheres were leached from liver, muscle, adrenal and thyroid tissues during the induction of hypocalcaemia. Hypocalcaemia reduced blood flow rates by more than 58 per cent in all tissues examined except kidney (48 per cent), heart (53 per cent), lung (10 per cent) and bladder (47 per cent) and reduced cardiac output from 3.70 +/- 0.19 (mean +/- SE) litres min-1 to 2.39 +/- 0.14 litres min-1. Approximately 2.2 per cent of cardiac output passed through arteriovenous shunts. This percentage was unaffected by hypocalcaemia. PMID- 3103179 TI - Influence of a deficient supply of magnesium during the dry period on the rate of calcium mobilisation by dairy cows at parturition. AB - The influence of a deficient magnesium supply during the dry period on the ability of dairy cows to mobilise calcium at parturition was investigated. The daily rations pre-partum consisted of 6 kg grass hay, and 4 kg concentrates containing either 1.58 per cent magnesium (HMg) or 0.22 per cent magnesium (LMg). Nine cows of parity one to six received the LMg diet and 10 cows of parity one to seven the HMg diet. Both rations provided 1.40 times maintenance on an energy basis and contained 4 per cent potassium in the dry matter. Throughout the dry period the mean concentration of magnesium in the plasma of the LMg group was significantly lower than in the HMg group and at parturition the mean plasma concentrations were 0.65 mmol litre-1 and 1.16 mmol litre-1, respectively. After parturition two cows in the LMg group showed clinical signs of hypocalcaemia but none of the HMg group did so. Cows of the LMg group had a lower mean rate of calcium mobilisation (0.27 mmol min-1) than those of the HMg group (0.34 mmol min 1) but the difference could not be explained by differences in bone turnover as reflected by urinary hydroxyproline excretion. Such a reduced rate of calcium mobilisation may be a contributory factor in the high incidence of milk fever in some herds fed inadequate magnesium in the dry period. PMID- 3103181 TI - Pulmonary diffusing capacity for carbon monoxide by rebreathing in awake dogs. AB - In order to reduce the effects of functional inhomogeneities on the determination of pulmonary diffusing capacity (transfer factor) for CO (DLCO), DLCO was measured by a rebreathing method in 5 awake chronically tracheostomized dogs (mean body weight 28 kg) during high ventilation (15-25 times above normal) induced by hypoxia, hypercapnia, exercise, or their combinations. The animals rebreathed for 15 s a mixture containing 1% He, 0.1% C18O, with CO2 and O2 concentrations adjusted to maintain end-tidal PCO2 and PO2 close to their prerebreathing values. Gas partial pressures in the trachea were continuously monitored by mass spectrometry. DLCO was calculated from C18O equilibration kinetics, effective ventilation (obtained from He mixing kinetics) and lung volume (obtained from He dilution). Each of the factors, hypoxia, hypercapnia and exercise, contributed to increasing DLCO. During exercise in combined hypoxia and hypercapnia, DLCO (mean +/- SE) was 71.7 +/- 1.8 ml/(min X Torr). The mechanisms for increases in DLCO might have involved improvement of diffusion conditions, decrease of functional inhomogeneities and reduction of the effects of functional inhomogeneities. The highest DLCO values were close to values derived from morphometry. PMID- 3103182 TI - Respiration and blood gases in the duck exposed to normocapnic and hypercapnic hypoxia. AB - Cardio-respiratory parameters were measured in the unrestrained, unanesthetized duck by whole body plethysmography during exposure to varied levels of inspired hypoxia without or with (3.7%) CO2. At any level of inspired PO2 (PIO2), ventilation (VE) was larger with CO2 inhalation, leading, for PIO2 greater than 50 Torr, to higher levels of arterial PO2 (PaO2) and O2 content (CaO2). Below PIO2 of 50 Torr, the (PI-Pa)O2 difference without CO2 reached a value as low as 5 Torr which was not diminished by further stimulation of VE by inhaled CO2. Without CO2 inhalation at this deep hypoxic level the ensuing hypoxia-induced respiratory alkalosis was partly compensated by lactacidosis, whereas CO2 inhalation resulted in markedly lower blood pH leading to significantly lower arterial and venous O2 content (Bohr effect). As a result, the deepest level of hypoxia tolerated without CO2 inhalation, 30 Torr, is significantly deeper than that, 36 Torr, tolerated when CO2 is inhaled. The data suggest that a number of factors contribute to the high hypoxia tolerance in birds, e.g. the effectiveness of parabronchial ventilation and the tolerance of low arterial PCO2 levels, whereby part of the lactacidosis is compensated. PMID- 3103183 TI - Effect of parasympathetic blockade on ventilatory and cardiac depression induced by opioids. AB - We have previously shown that delta-opioid agonists decrease ventilation and heart rate. Because of these results and the known interactions between opioid and acetylcholine metabolism, we hypothesized that opioids induce cardiorespiratory changes via the parasympathetic nervous system. To test this hypothesis, we administered atropine sulfate (systemically) at maximal effect of D-Ala-D-Leu-enkephalin (DADLE; a preferential delta-opioid agonist), injected intracisternally, and examined its effect on cardiorespiratory function. All experiments were performed on chronically instrumented and conscious adult dogs. Mean instantaneous minute ventilation or VT/TTOT decreased and PaCO2 increased after DADLE; atropine had little effect on these changes. Naloxone, even in small doses, reversed opioid effects on VT/TTOT and PaCO2. Atropine, however, reversed the DADLE-induced depression in cardiac rate. In doses that reversed this cardiac depression, atropine had no effect on cardiorespiratory function at rest, i.e., with no prior administration of DADLE. We conclude that DADLE decreases heart rate by increasing parasympathetic activity to the heart and induces hypoventilation by a different mechanism. We speculate that the opioid-induced ventilatory depression is due to either direct opioid action on central respiratory regulation or parasympathetic non-muscarinic or non-cholinergic mediating mechanisms. PMID- 3103184 TI - Diffusion limitation and limitation by chemical reactions during alveolar capillary transfer of oxygen-labeled CO2. AB - A major difficulty in the measurement of carbon dioxide diffusing capacity is the development of significant CO2 back pressure within the capillary. The use of oxygen-labeled CO2 limits this back pressure due to rapid dilution of the label into the water pool by isotopic exchange. We demonstrated the use of C16O18O to measure DCO2 (Schuster, 1985). A major question from that study is whether the isotope measures a true membrane diffusing capacity or is limited by back reaction. In this study we examine the diffusing capacity of doubly 18O-labeled carbon dioxide, C18O2, a species in which the kinetics of isotopic exchange in pulmonary blood is higher than that of C16O18O. Eighteen single breath experiments were performed on two resting male subjects whose CO2-transfer kinetics was previously studied with C16O18O (Schuster, 1985). Following expiration to residual volume the subjects inspired a gas mixture containing 20% O2 and 1.5-2.6% C18O2. After holding their breath for 0.4-17 sec they exhaled into a tube and the end-expired gas was analysed by mass spectrometry. The time course of the C18O2 disappearance from alveolar gas showed a biexponential characteristic as that which had been measured with C16O18O, but C18O2 disappeared faster. The mean value of the diffusing capacity of C18O2 amounts to 1102 ml mmHg-1 X min-1. It is 228 +/- 163 ml mmHg-1 X min-1 greater than that of C16O18O. This significant difference suggests that: DC16O18O is limited in part by isotopic exchange reactions; the observed DC18O2 may be taken as a new lower limit for DMCO2, higher than values established from other techniques; the decarboxylation of bicarbonate in red cells is not a rate limiting step for CO2 exchange. PMID- 3103185 TI - Changes in ventilation and breathing pattern produced by changing body temperature and inspired CO2 concentration in turtles. AB - Respiratory minute ventilation (VE), breathing pattern, oxygen consumption (VO2) and arterial blood gases and pH were measured in freshwater turtles (Chrysemys picta) at 10, 20 and 30 degrees C while the animals breathed gases of varying CO2 concentration (FICO2 = 0, 2, 4, 6 and 8%). Increasing body temperature produced unequal increases in VE and VO2 such that VE/VO2 decreased. This relative hypoventilation led to a rise in PaCO2 and fall in pHa. Increasing FICO2 at all temperatures greatly elevated VE. The magnitude of this response increased with increasing temperature. Thus, paradoxically, there was an increase in both PaCO2 and CO2 sensitivity with increasing temperature. Increases in VE due to increases in temperature were primarily due to a shortening of the periods of breath holding. Although changes in VT contributed to changes in VE with increasing FICO2, the changes in f, due to shortening the periods of breath holding, contributed twice as much. In relative terms, increasing temperature had no effect on the CO2 response of any respiratory variable. Analysis of the data indicates that all changes which occurred in VE, PaCO2 and pHa with changes in body temperature can be explained by equal Q10 effects of roughly two on both metabolic rate and ventilatory sensitivity to changes in PaCO2. PMID- 3103186 TI - Ventilatory responses to respiratory and metabolic acid-base disturbances in cats. AB - To determine the relative importance of the peripheral and central chemoreceptors in the ventilatory response to acute metabolic acid-base disturbances we measured the normoxic ventilatory response to acute respiratory and metabolic acidosis and alkalosis in 10 chloralose-urethane anesthetized cats using a technique of vertebral artery perfusion that allows one to independently manipulate the PaCO2, PaO2 and the H+ concentration of the blood in the systemic circulation (peripheral) and the blood perfusing the brain stem (central) (Berkenbosch et al., 1979). The ventilation could be satisfactorily described by a linear function of the peripheral and central arterial H+ concentration and the central PaCO2. Mean values (+/- SEM) found for the peripheral arterial H+ sensitivity and the isocapnic central arterial H+ sensitivity were 26.0 +/- 3.2 and 12.7 +/- 1.8 ml X min-1 X nM-1, respectively; the isohydric central arterial CO2 sensitivity was 545.9 +/- 96.7 ml X min-1 X kPa-1. We conclude that in the ventilatory response to an acute metabolic acid-base disturbance both the peripheral and central chemoreceptors play a role. However, the sensitivity of the peripheral chemoreceptors to isocapnic changes in the arterial H+ concentration is twice as large as the sensitivity of the central chemoreceptors. It is argued that in the adaptation of the ventilation to an acute metabolic acidosis the stimulatory effect of the peripheral chemoreceptors is counteracted by a diminished stimulation of the central chemoreceptors. PMID- 3103187 TI - Acute effects of hypercapnia and hypoxia on minute ventilation in unrestrained Weddell seals. AB - We studied the ventilatory response to hypoxia and hypercapnia in five freely diving juvenile Weddell seals (age = 2 years) at McMurdo Station, Antarctica. The ventilatory response to CO2 was brisk, with minute ventilation increasing as a linear function of end tidal CO2 with an average slope of 3.1 L X (min X mm Hg) 1. The ventilatory response to hypoxia was small and variable. End tidal PO2 values as low as 28 mm Hg provoked at most a doubling of minute ventilation. These results were supported by the observation that elevated end tidal CO2 always inhibited voluntary diving whereas low PO2 values did not. Comparison of the Weddell seals' CO2 responsiveness to that of other mammals reveals similar CO2 sensitivity. We conclude that CO2 is the major determinant of ventilatory drive in wild Weddell seals. PMID- 3103188 TI - [The effect of the residual water in dentin tubules on the adhesion of a resin bonding system]. PMID- 3103189 TI - [Infection, antibiotic therapy and hemorrhagic diathesis]. PMID- 3103190 TI - [Cervical myelopathy as a result of ossification of the posterior longitudinal ligament (4 cases)]. AB - Ossification of the posterior longitudinal ligament was demonstrated in four caucasian males with progressive myelopathy. Such a condition is not uncommon in Japan, but has rarely been reported in caucasian subjects. It is not related to spondylarthrosis. Clinical course is usually protracted and can be worsened by mild trauma. Computerized tomography is the best diagnostic tool. Anterior decompressive surgery is theorically warranted in cases of severe myelopathy. Multisegmental laminectomy was performed on two patients, but was followed by little improvement. We discuss the relation between this condition and ankylosing spinal hyperostosis. PMID- 3103191 TI - Posttraumatic endophthalmitis: the emerging role of Bacillus cereus infection. AB - Endophthalmitis resulting from nonsurgical penetrating trauma to the eye is a relatively uncommon infection in the United States. Data are limited, but most recently published series have attributed the highest incidence of infection to gram-positive organisms, in particular Staphylococcus epidermidis. Fungal causes have been reported far less frequently. Bacillus species are being recognized increasingly as major causes of posttraumatic ocular disease, with rates of infection often making them the second most commonly isolated organisms. Bacillus cereus, an especially virulent pathogen, causes a fulminant endophthalmitis characterized by rapid destruction of intravitreal contents and a uniformly poor visual outcome. Certain toxins elaborated by the organism may contribute to its particular virulence. The currently recommended approach to suspected posttraumatic infection involves early use of diagnostic vitrectomy and intraocular culture, use of intravitreal antibiotics, and combination treatment with systemic and periocular antibiotics. PMID- 3103192 TI - Listeria rhombencephalitis mimicking tuberculous meningitis. AB - A previously healthy man developed a progressive neurologic illness characterized by an "aseptic meningitis syndrome," progressive hypoglycorrhachia, and severe brain-stem dysfunction. Initial dramatic response to antituberculosis therapy supported the diagnosis of tuberculous basilar meningitis; however, Listeria monocytogenes eventually grew in a blood culture, and the patient recovered following intravenous ampicillin therapy. The entity of listerial rhombencephalitis should be considered as a treatable cause of acute, progressive brain-stem meningoencephalitis. PMID- 3103193 TI - [Bacterial, mycotic and parasitic etiological agents in diarrheal disease of children]. PMID- 3103194 TI - [The principal antitubercular agents]. PMID- 3103195 TI - [A care record and planning for long-term patients]. PMID- 3103196 TI - [Adjuvant disease in rats experimentally infected with Trypanosoma cruzi]. PMID- 3103197 TI - Experimental infection with Schistosoma mansoni of Biomphalaria straminea from different parts of the Northeast of Brazil. PMID- 3103198 TI - Treatment of patients with schistosomiasis mansoni: a double blind clinical trial comparing praziquantel with oxamniquine. PMID- 3103199 TI - How we draw arterial blood without bleeding the patient. PMID- 3103200 TI - [Diabetic acidoketosis in adults]. PMID- 3103201 TI - [Bone and aluminum]. PMID- 3103202 TI - [The neuropsychiatry service in current primary care: an investigation including critical results (II)]. PMID- 3103203 TI - Duodenal mucosal bicarbonate secretion in humans: a brief review. AB - The human proximal duodenum serves as the crucible for the neutralization of gastric acid. Methods have been developed and validated that permit isolation of 4-cm segments of either the proximal or distal duodenum. These isolated segments were free of contamination from gastric, pancreatic, and biliary secretions. At rest the healthy human proximal duodenum produced approximately 175 mumol cm-h: or, assuming that the duodenal bulb is approximately 4 cm in length, 700 mumol h. The distal duodenum (the third part) produced significantly less bicarbonate, approximately 25 mumol/cm-h. HCl produced a prompt and sustained increase in bicarbonate output from both duodenal segments. Bicarbonate output was less in the distal duodenum, indicating a proximal-to-distal gradient. Synthetic prostaglandin E1 caused a dose-related increase in output. Substitution of the NaCl perfusate with Na2SO4 produced a brief decrease, suggesting a chloride bicarbonate exchange mechanism. Vasoactive intestinal polypeptide significantly increased proximal duodenal bicarbonate output. Bicarbonate production by the duodenal mucosa is probably an important defensive factor in maintaining mucosal integrity. PMID- 3103204 TI - Strategies for preventing aspirin-induced gastric bleeding. AB - Prostaglandins protect the gastric mucosa in animals, but the evidence of an effect independent of pH changes in man is not overwhelming. Gastrointestinal bleeding because of non-steroidal anti-inflammatory drugs is a major clinical problem, which we have investigated in a model system measuring bleeding rates caused by short-term administration of aspirin. Of the various strategies tested, only those that elevated intra-gastric pH reduced aspirin-induced bleeding. PMID- 3103205 TI - The role of mucus in the protection of the gastroduodenal mucosa. AB - There is good evidence that the adherent mucus plays an important role in the protection of gastroduodenal mucosa from the endogenous aggressors acid and pepsin. Adherent mucus provides a stable unstirred layer which supports surface neutralization of acid by mucosal bicarbonate output and acts as a permeability barrier to luminal pepsin. The adherent mucus layer is continuous. True thickness of the mucus layer and its continuity can only be observed on unfixed sections of mucosa, since histological fixatives and preparation for electron microscopy can cause dehydration and shrinkage of the mucus gel. The structure of adherent gastric mucus is deficient in patients with peptic ulcer disease because of decreased polymerization of the component glycoproteins. This impairment of the mucus barrier is associated with raised amounts of pepsin 1, which digests the mucus layer more aggressively than the major pepsin, pepsin 3, under conditions that pertain both in the stomach (pH 2) and duodenum (pH 4-5). Adherent mucus does not appear to offer much protection against exogenous damaging agents, e.g. alcohol and aspirin. These agents permeate the mucus barrier, damaging the underlying epithelium. The subsequent epithelial repair process is protected by a gelatinous coat over ten times thicker and distinct from the normal adherent mucus layer. Our recent studies show this gelatinous coat to be primarily a fibrin-based gel with mucus and necrotic cells. PMID- 3103206 TI - Neither interleukin 2 nor gamma interferon directly promote growth or differentiation of mouse B cells. AB - The roles of interleukin 2 (IL-2) and gamma interferon (IFN-gamma) as direct mediators of B-cell growth and differentiation were analysed. Products of cloned genes were used in both cases. The use of flow cytometric assays coupled with density fractionation of responding splenic B-cell populations enabled both the characterization of B cells responding to various stimuli and the estimation of their frequency. B cells responding to non-IL-2 related lymphokines promoting growth and differentiation were restricted to low buoyant density fractions. In addition, these cells expressed densities of IL-2 receptor determinants comparable to those found on T cells, although, IL-2 did not support their growth or differentiation. The inability to demonstrate any direct effect of either IL-2 or IFN-gamma on B cells in any state of activation suggests that their physiological roles are mediated through additional cell types. PMID- 3103207 TI - Selection of beta-lactamase producers during cephalosporin and penicillin therapy. AB - Treatment failures due to beta-lactamase producing strains of Enterobacter cloacae, Proteus vulgaris, Citrobacter freundii and Pseudomonas aeruginosa are frequently reported. It is difficult, however, to determine the underlying mechanism of resistance development. Different beta-lactam drugs, such as cephalosporins and penicillins have different ecological impacts on the infections and physiological flora of patients. They select in different ways although the mutation frequency of strains towards beta-lactamase production is not affected by these drugs. Thus in a specific process of selection one has to consider the mechanism and frequency of changes in the beta-lactamase production, the selective power of the different drugs (relation of drug concentration to the MIC for possible mutants or induction of beta-lactamase), selection of resistance in the physiological flora of patients, spread of such mutants to other patients and in the hospital environment, and the stability of beta-lactamase production. As each antibiotic has the potential of selecting mutants and in the case of beta lactam drugs the more powerful ones select for mutants which produce a beta lactamase that is more stable against less powerful drugs, a careful selection of drugs together with an effective infection control is mandatory. PMID- 3103208 TI - Emergence of resistant bacterial strains during treatment of infections in the respiratory tract. AB - In order to investigate the frequency of the emergence of resistance during treatment, 1,403 episodes of lower respiratory infection were studied in a General Hospital with three departments of Chest Medicine in a period of four years. In 650 episodes the pathogen was isolated and in 82 of those failure of therapy was accompanied by emergence of resistance to the agent used. Factors associated with this phenomenon were: intensive care, tracheostomy, involvement of Pseudomonas aeruginosa, Enterobacter spp., Serratia marcescens, Staphylococcus aureus or Acinetobacter calcoaceticus, use of antipseudomonas penicillins, cefotaxime (especially when used in P. aeruginosa infections) and co-trimoxazole and monotherapy as opposed to appropriate combination therapy in patients with nosocomial pneumonia. PMID- 3103209 TI - Bengt E. Gustafsson memorial lecture. Function of the normal human microflora. AB - The normal human microflora maintains a delicate balance between its constituent parts, numbering 10(11) bacteria per gram with over 400 different species. Certain metabolic functions and enzyme activities can be attributed to the microflora, and these play a role in metabolizing nutrients, vitamins, drugs, endogenous hormones and carcinogens. Our laboratory has studied estrogen and cholesterol metabolism and activation of colon carcinogens. Three techniques to change the flora and its enzymatic activities have been used. Switching the diet from an omnivore diet to a vegetarian diet decreases bacterial deconjugating enzymes in the intestine. Administering antibiotics also suppresses the metabolic activity of the microflora. Similar suppressive effects can be achieved by feeding a human strain of Lactobacillus that implants in the gastrointestinal tract. Manipulation of these various modalities can maximize the beneficial activities of the intestinal microflora. PMID- 3103210 TI - Nosocomial consequences of antibiotic usage. AB - In 1979, seven years after introduction of gentamicin into the greek market, resistance in Pseudomonas aeruginosa rose in Laiko General Hospital to an incidence of 55% of the isolates. Gentamicin then was the first line antibiotic. In 1983, three years after amikacin was brought onto the market and while it represented 3/5 of all aminoglycoside consumption, resistance against it in strains of Pseudomonas rose suddenly to 23%. However, amikacin prescription was not restricted and, in 1985, resistance rate, including all aminoglycosides and the 3rd generation cephalosporins, exceeded 50%. By analysing all available data, it was evident that: Urine predominates in the isolation of multiresistant strains, while in 1/2 of bacteraemias amikacin-resistant strains are implicated. The ICU is the most common source of isolation and similar strains are spread in all hospital wards. Multiresistant strains are virulent since they were incriminated for a 11% death rate. In 60% of amikacin resistant strains AAC (6') I was detected. Among multiresistant strains serotype O:12 predominated. From the hospital pharmacy data, it was evident that antibiotic consumption refers to greater than 60% of hospital admissions, and amikacin, netilmicin and newer cephalosporins are the first line antibiotics. It is evident that urgent changes are needed in the antibiotic policies in the Laiko General Hospital. PMID- 3103211 TI - In vivo significance of bacteriocins and bacteriocin receptors. AB - Bacteriocins are protein or protein-complex antibiotics produced by a wide variety of bacterial species. By conventional definition, bacteriocins differ from most other antibiotics in that the producer strain is immune to the action of its own bacteriocin and the inhibitory activity of individual bacteriocins is directed only to bacteria which are closely related to the strains which produce them. Bacteriocin production is regulated by plasmid or chromosomal elements and bacteriocin activity is initiated by adsorption of bacteriocin to specific outer membrane receptors on susceptible cells. In Darwinian terms, production of bacteriocin by a bacterial strain, within a particular ecological niche, could be considered advantageous by ensuring elimination of other closely related, and thus competitive, bacteria. In contrast, conservation of bacteriocin receptors appears suicidal if their only function is to initiate cell death. The paper will illustrate the ubiquity of bacteriocins and discuss evidence for their in vivo function in terms of bacterial survival. Evidence will also be presented to indicate that bacteriocin receptors in Escherichia coli and Pseudomonas aeruginosa have important alternative physiological functions in outer-membrane mediated nutrient uptake, particularly with respect to bacterial iron metabolism. PMID- 3103212 TI - [The exercise test in pulmonology]. AB - Pulmonary exercise testing is intended to evaluate the functional capacity of a patient and to identify the limiting factors. Its indications cover the whole spectrum of the diseases associated with dyspnea. Many clinical situations can easily be resolved during a non-invasive test merely by measuring ventilation, heart rate and systemic blood pressure. For the determination of pulmonary gas exchange, samples of arterial blood and expiratory O2 and CO2 fractions are necessary. In comparison with other pulmonary function tests, exercise testing is the only technique which provides overall information on the many adaptive mechanisms triggered by exercise. Consequently, it is of special value in distinguishing between pathophysiological states. PMID- 3103213 TI - [Reflections on a burning subject, doping]. PMID- 3103214 TI - Commodity, the bias of the world. AB - This paper is a survey primarily for non-specialists of the "value of life" controversy, and its relevance to the environment. Many projects which affect the environment also cause or prevent human deaths. For explicit inclusion of the effects on mortality in the cost-benefit assessment, and for consistency within and between projects, monetary valuation is required. There are objections to "pricing life" and to the various methods, but the willingness to pay for risk reduction seems the best approach available. Some recent UK studies suggest a minimum value of 2 million pounds per death. PMID- 3103215 TI - Isolation and structure of a covalent cross-link adduct between mitomycin C and DNA. AB - A DNA cross-link adduct of the antitumor agent mitomycin C (MC) to DNA has been isolated and characterized; the results provide direct proof for bifunctional alkylation of DNA by MC. Exposure of MC to Micrococcus luteus DNA under reductive conditions and subsequent nuclease digestion yielded adducts formed between MC and deoxyguanosine residues. In addition to the two known monoadducts, a bisadduct was obtained. Reductive MC activation with Na2S2O4 (sodium dithionite) leads to exclusive bifunctional alkylation. The structure of the bisadduct was determined by spectroscopic methods that included proton magnetic resonance, differential Fourier transform infrared spectroscopy, and circular dichroism. Formation of the same bisadduct in vivo was demonstrated upon injection of rats with MC. Computer-generated models of the bisadduct that was incorporated into the center of the duplex B-DNA decamer d(CGTACGTACG)2 indicated that the bisadduct fit snugly into the minor groove with minimal distortion of DNA structure. A mechanistic analysis of the factors that govern monofunctional and bifunctional adduct formation is presented. PMID- 3103216 TI - Regulation in vitro of metallothionein gene binding factors. AB - Mouse nuclear factors that bind to an upstream metal regulatory element of the mouse metallothionein-I gene have been identified by DNA footprinting and oligonucleotide band shift assays. The formation of complexes at this site can be activated 20- to 40-fold by the vitro addition of ionic cadmium. The activation reaction is rapid, reversible by a metal chelator, and may involve multiple proteins. These results suggest that the initial step in cadmium detoxification is an interaction between the metal and nuclear DNA-binding factors leading to an increase in metallothionein gene transcription. The ability to observe metal activation in vitro makes this a powerful system to study the biochemistry of eukaryotic gene regulation. PMID- 3103217 TI - Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. AB - An accelerated rate of glucose transport is among the most characteristic biochemical markers of cellular transformation. To study the molecular mechanism by which transporter activity is altered, cultured rodent fibroblasts transfected with activated myc, ras, or src oncogenes were used. In myc-transfected cells, the rate of 2-deoxy-D-glucose uptake was unchanged. However, in cells transfected with activated ras and src oncogenes, the rate of glucose uptake was markedly increased. The increased transport rate in ras- and src-transfected cells was paralleled by a marked increase in the amount of glucose transporter protein, as assessed by immunoblots, as well as by a markedly increased abundance of glucose transporter messenger RNA. Exposure of control cells to the tumor-promoting phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) for 18 hours had a similar effect of increasing the rate of glucose transport and the abundance of transporter messenger RNA. For ras, src, and TPA, the predominant mechanism responsible for activation of the transport system is increased expression of the structural gene encoding the glucose transport protein. PMID- 3103218 TI - Brain damage by AIDS under active study. PMID- 3103219 TI - Regional changes in calcium underlying contraction of single smooth muscle cells. AB - The role of calcium in regulating the contractile state of smooth muscle has been investigated by measuring calcium and contraction in single smooth muscle cells with the calcium-sensitive dye fura-2 and the digital imaging microscope. The concentration of free calcium in the cytoplasm increased after stimulation of the cells by depolarization with high potassium or by application of carbachol. Changes in calcium always preceded contraction. The increase in calcium induced by these stimuli was limited to less than 1 microM. Calcium within the nucleus was also subject to a limitation of its rise during contraction. Intranuclear calcium rose from 200 nM at rest to no more than 300 nM while cytoplasmic calcium rose to over 700 nM. These apparent ceilings for both cytoplasmic and intranuclear calcium may result either from negative feedback of calcium on cytoplasmic and nuclear calcium channel gating mechanisms, respectively, or from the presence of calcium pumps that are strongly activated at the calcium ceilings. PMID- 3103220 TI - Complications of parenteral nutrition. AB - There have been no controlled studies that clearly document a beneficial effect of TPN on neonatal mortality and morbidity. Beneficial effects such as reducing the time required to achieve some targeted weight and enhancing positive nitrogen balance are used in support of TPN. The positive opinion about TPN is strongly supported by the experience in surgical patients with GI disorders. It is not surprising that use of TPN is a complex therapy in newborn patients. It is an essential therapy in many patients if nutrition is to be maintained that permits growth and promotes resolution of other chronic problems. Accurate determination of the requirements for TPN is difficult, while complications are not always preventable by simply monitoring blood chemistries. Because of the acute or long term and potentially lethal complications, there is need for further understanding in parenteral nutrition. PMID- 3103221 TI - Necrotizing enterocolitis: a complication of prematurity. PMID- 3103222 TI - [Endogenous prostaglandins mediating adaptive cytoprotection on gastric mucosa by pepsin]. PMID- 3103223 TI - [Role of prostacyclin and thromboxane A2 in adaptive cytoprotection of gastric mucosa by pepsin]. PMID- 3103224 TI - Neurofibromatosis and multiple skull defects: a case report. PMID- 3103225 TI - Case report 398: Friction by pes anserinus. PMID- 3103226 TI - Anaerobic bacteria in habitats other than man. PMID- 3103227 TI - Methanogenic bacteria and methane production in various habitats. PMID- 3103228 TI - Anaerobic bacteria of the normal intestinal microflora of animals. PMID- 3103229 TI - Some problems in the identification and taxonomy of clostridia. PMID- 3103230 TI - Microbial adhesion and colonization within the digestive tract. PMID- 3103231 TI - Nitrogen metabolism in the animal gut. PMID- 3103233 TI - Involvement of intestinal anaerobes in the spoilage of red meats, poultry and fish. PMID- 3103234 TI - Anaerobes in relation to foods of plant origin. PMID- 3103232 TI - Anaerobic diseases of animals. PMID- 3103235 TI - Important properties in the differentiation of gram positive non-sporing rods in the genera Propionibacterium, Eubacterium, Actinomyces and Bifidobacterium. PMID- 3103236 TI - Non-sporing and sporing anaerobes in dairy products. PMID- 3103237 TI - Methods for the isolation and identification of anaerobes. PMID- 3103238 TI - Preservation of anaerobes. PMID- 3103239 TI - Characterization of anaerobic cocci. PMID- 3103240 TI - Current status of the taxonomy of gram negative non-sporing anaerobic rods of the family bacteroidaceae. PMID- 3103241 TI - Other anaerobes--curved and spiral organisms. PMID- 3103242 TI - Who cares what care?: an inverse interest law? AB - The paper attempts to systematise some of the ideas on medical dominance as the inverse interest law, which is broadly seen as the more commonplace the problem and the more people affected, the less will be the medical interest. The law or rather laws are exemplified by reference to the symptom iceberg, health education and welfare, hospital expenditure, priority groups and community care and class, locality and ethnicity. The inverse interest laws, which ensure the operation of the inverse care law, are seen as products of medicine definition and practice in relation to their containing society. PMID- 3103243 TI - Geriatric care and distributive justice: problems and prospects. PMID- 3103244 TI - The hormonal and morphological events of stimulated cycles in an in vitro fertilisation programme. AB - A better understanding of the physiological processes involved in the stimulated cycle for successful harvesting of mature eggs in an in vitro fertilisation programme is a prerequisite for obtaining good pregnancy results. The hormonal levels of oestradiol, luteinising hormone (LH) and follicle-stimulating hormone correlated with ultrasonographic studies of follicular growth, were followed during an in vitro fertilisation cycle giving an overall pregnancy rate of 32% per transfer procedure. The combined use of clomiphene citrate (Clomid; Mer National) and human post-menopausal gonadotrophin (Pergonal; Script Intal) produces an average of 5.96 follicles per patient. Human chorionic gonadotrophin (HCG) was given prior to the oestrogen peak and no spontaneous LH peak occurred before the day of the HCG injection. Timing of this injection needs to be synchronised with definite hormonal and ultrasonography values. PMID- 3103245 TI - A comparison of cefotaxime versus cefamandole in prophylaxis for surgical treatment of the biliary tract. AB - Fiscal considerations prompted comparison of cefotaxime (a third generation cephalosporin) with cefamandole (a second generation cephalosporin) for prophylaxis in the surgical treatment of the biliary tract. One hundred and eight patients who underwent an operation upon the biliary tract received three 1 gram doses of cefotaxime (54 patients) or cefamandole (54 patients) at induction of anesthesia and then one and three hours later. The study was prospective, blinded and randomized. The groups (cefotaxime versus cefamandole) were statistically comparable for age, sex, diagnosis, type and duration of operation and positive cultures. The most prevalent bacteria isolated from qualitative aerobic and anaerobic cultures of bile and the wall of the gallbladder were Escherichia coli, Streptococcus and Klebsiella. The incidence of bactibilia in patients with one of these conditions was: 75 per cent for cancer; 69 per cent for patients more than 60 years old; 33 per cent for jaundice; 58 per cent for pancreatitis; 60 per cent for exploration of the common bile duct, and 22 per cent for acute cholecystitis. Microbiologic agar diffusion assays of tissue from the wall of the gallbladder, subcutaneous fat and rectus muscle and samples of bile and serum obtained 30 minutes after the second dose of antibiotic showed a statistically significant greater concentration of cefamandole in the wall of the gallbladder. Otherwise there was no difference between the concentration of cefamandole and cefotaxime. The groups showed no statistical difference for temperature of more than or equal to 38 degrees C. on two consecutive measurements, postoperative wound and urinary infections, postoperative hospital stay and days in the intensive care unit and incidence of readmission within a month. Prophylactic use of cefotaxime in a three dose regimen provided no advantage in prophylaxis compared with cefamandole. PMID- 3103246 TI - Endoscopic placement of a weighted tip feeding tube in complex surgical patients. PMID- 3103247 TI - Persistent memory loss following section of the anterior fornix in humans. A historical review. AB - Searching the medical literature for persistent memory loss following section of the anterior fornix in humans, 13 reports were found and reviewed. They comprised 193 patients of whom 180 underwent fornicotomy for the treatment of epilepsy, and 13 underwent removal of third ventricle colloid cysts. Only 4 were reported to have persistent memory loss postoperatively and they were in the colloid cyst group. Within the limitations inherent to this type of analysis and to the problems of detection and quantification of memory deficits, the reviewed material supports the hypothesis that with anterior fornix section we are only interfering with a part of the structural system subserving memory and that the tumor, the surgical trauma, or other destructive pathology, or a combination of factors including the variability of neural localization, may cause persistent memory loss by additional damage to structures other than the anterior fornix. Language and geographical barriers may explain the apparent failure in communication between early investigators. PMID- 3103248 TI - Chemical respiratory drive as a determinant of postoperative ventilation in the non-Pickwickian obese patient. AB - Hypercapnia in patients with pulmonary disease is believed to result from an interaction between mechanical lung impairment and intrinsic chemical respiratory drive. We tested this hypothesis in this study by examining the ventilatory (delta VE/delta PCO2) and occlusion pressure (delta P100/delta PCO2) responses to CO2 in 12 obese patients with no history of alveolar hypoventilation and correlating these with their ventilatory responses to abdominal surgery. Preoperatively the mean vital capacity (VC) was 78% +/- 6% standard error of the mean predicted, the delta VE/delta PCO2 was 1.56 +/- 0.26 L/min/torr, delta P100/delta PCO2 was 0.25 +/- 0.08 cm H2O/torr, the mean PaCO2 37.9 +/- 1.1 mm Hg, and mean PO2 77.6 +/- 3.7 mm Hg. Postoperatively the VC decreased to 56% +/- 6% of the preoperative value. PCO2 values at 24 hours increased in six patients, were unchanged in three, and decreased in three patients. However, over the entire spectrum of PCO2 change, both indexes of CO2 chemosensitivity correlated strongly with the postoperative change in PCO2 (r = -0.86 for delta VE/delta PCO2 and r = -0.66 for delta P100/delta PCO2). All six patients with a delta VE/delta PCO2 of 1.5 L/min/torr or less manifested postoperative increases in PCO2, while those with greater values did not (p = 0.005). In contrast, neither preoperative nor postoperative VC showed high correlations with postoperative PCO2 (r = -0.56 and -0.43, respectively). Thus ventilatory responses to CO2 predicted postoperative PCO2 at both ends of the spectrum; low responders hypoventilated while high responders hyperventilated. We conclude that in obese subjects, CO2 chemosensitivity plays a permissive role in determining the net ventilatory responses to situations that either mechanically load the respiratory system or modulate ventilation such as postoperative pain or analgesia. PMID- 3103249 TI - Perforated appendix: an unusual coagulopathy. PMID- 3103250 TI - [Drug information. Drug treatment can now replace castration in prostatic cancer]. PMID- 3103251 TI - [News of classification systems applied to resource management]. PMID- 3103252 TI - In vitro effect of a mucolytic thiol agent on the activity of polymorphonuclear leucocyte elastase and antileucoprotease. AB - We have studied the effects of the mucolytic thiol agent mercapto ethanesulphonate (mesna) on the activity of both polymorphonuclear leucocyte (PMN) elastase and antileucoprotease in vitro. In all tests a specific synthetic substrate was used to measure elastase activity, which was then related to enzyme activity in the absence of mesna. The relative elastase activity decreased to 67.5% of control values after the enzyme had been incubated in a 120 mmol/l mesna solution. In the sol phase of purulent sputum, elastase activity decreased to 45% after the sol phase had been incubated in a 600 mmol/l mesna solution. The inability to reverse the inhibition of mesna by increasing the substrate concentration indicated that mesna acts as a non-competitive inhibitor of PMN elastase. Incubation of elastase with antileucoprotease reduced the relative elastase activity to 21%. When antileucoprotease was preincubated in a 60 mmol/l mesna solution under identical assay conditions, a relative elastase activity of 39% was observed. Inhibition experiments with mesna treated antileucoprotease, in which sulphydryl groups were blocked with iodoacetamide, strongly suggested that the dissociation constant (Ki) of the fraction of antileucoprotease that retains activity after the incubation with mesna was not changed. Elastase inhibitory activity in mucoid sol phase, which can be ascribed mainly to antileucoprotease, decreased to 53% after incubation with mesna at a concentration of 960 mmol/l. Incubation of PMN elastase/antileucoprotease complex with mesna did not result in any release of active PMN elastase from the antileucoprotease. It is concluded that mesna and other thiol compounds, when locally administered, may influence the proteinase-antiproteinase balance in the airways by their effect on both PMN elastase and antileucoprotease. PMID- 3103253 TI - Aortic aneurysm caused by schistosomiasis. PMID- 3103254 TI - [Radiotherapy and chemotherapy in anal carcinoma]. PMID- 3103255 TI - [Congenital hypothyroidism. Current viewpoints and developments]. AB - Since 1978 neonatal screening on congenital hypothyroidism (CHT) is performed in The Netherlands. A combined T4 and TSH determination is used. This creates the possibility to detect secondary and tertiary hypothyroidism. The number of false positive cases is relatively high. This number decreases by adjusting the method of screening. Recent studies show a CHT incidence of 1:2100 newborns. In about 25% of these cases the CHT appears to be transient. Proceeding from the screening on CHT several investigations presented in this review are in progress. PMID- 3103256 TI - [Current developments in the treatment of growth delay using growth hormone]. AB - In this paper five new developments in the field of growth hormone (GH) deficiency and its treatment are discussed. Firstly, the changing concepts on the definition of GH deficiency are described. The main criteria for GH deficiency are a low growth velocity and a decreased GH secretion, but for none of these parameters clear limits can be drawn. Secondly, the results of GH therapy in children with normal GH responses to provocative stimuli are reviewed. Growth velocity does increase in many of these children, but it is not yet known if the final height will increase. Thirdly, new modes of administration are discussed, as well as the GH dosage and the frequency of injections. Daily subcutaneous administration seems to be superior in terms of growth promoting effect. The fourth new development, the production of biosynthetic GH, is certainly the most important. This will soon lead to an unlimited supply of GH with great consequences for the type of patients that will be treated and for the dosage that will be given. Finally, the pharmacological agents which can stimulate the GH secretion are described, particularly growth hormone releasing factor (GRF). The therapeutical use of GRF is still in an experimental phase. In the present circumstances it is very important that GH therapy be given in a well standardized way. For the time being concentration of patients into the centres of pediatric endocrinology will remain advantageous. PMID- 3103257 TI - Purification of rat retinol-binding protein using Blue Sepharose CL-6B. AB - Studies were conducted to isolate rat plasma retinol-binding protein, the specific transport protein for vitamin A in the rat. Retinol-binding protein was isolated from rat plasma by a new simple procedure using Blue Sepharose CL-6B, and highly purified retinol-binding protein was obtained. This procedure included DEAE-cellulose chromatography at pH 6.0, Sephadex G-75 gel filtration in the presence of 3.0 M urea, Blue Sepharose CL-6B affinity chromatography at pH 7.0 and finally Sephadex G-100 gel filtration at pH 7.4. The third step completely accomplished the dissociation and separation of retinol-binding protein from its complex with prealbumin and plasma albumin. This procedure is a significant improvement over previously published procedures, in which sample recycling and preparative polyacrylamide gel electrophoresis are necessary. The molecular weight, electrophoretic behaviour, ultraviolet and fluorescence spectra of the retinol-binding protein were similar to those appearing in other reports. PMID- 3103258 TI - Inhibitory effect of liposome-encapsulated penicillin G on growth of Listeria monocytogenes in mouse macrophages. AB - Administration of penicillin G encapsulated in liposomes inhibited the proliferation of Listeria which infected mouse intraperitoneal resident macrophages whereas free penicillin G and/or liposomes did not. This result suggests that administration of antibiotics encapsulated in liposomes is an effective treatment for the intracellular infection. PMID- 3103259 TI - Identification of human saliva by antisera to alpha-amylase in human salivary glands. AB - Amylase activities were detected significantly in saliva from human, macaques and rodents and slightly in the vegetable and fruit extracts. Dried stains on filter paper prepared from human and mammalian saliva, and the vegetable and fruit extracts were subjected to starch-iodine test and blue starch polymer-agar plate test. Both tests showed strong positive reactions with the macaque and rodent saliva stains as well as human, but the vegetable and fruit stains showed clear positive reactions only in the starch-iodine test. The results suggest that these tests are not specific for human saliva and that for screening test of saliva stains, blue starch polymer-agar plate test is more suitable than starch-iodine test. Rabbit antisera against alpha-amylase isolated from the human submaxillary glands were prepared. In double immunodiffusion test with the human and mammalian saliva, human and macaque saliva produced precipitation lines. Human saliva gave patterns of partial identity with saliva from Japanese monkey and crab-eating monkey and these two macaque saliva gave total identity with each other. Anti alpha-amylase sera absorbed with Japanese monkey saliva reacted only with human saliva. This suggested that the anti-alpha-amylase sera absorbed with macaque saliva make it possible to identify human saliva stain. PMID- 3103260 TI - Evidence that pyrrole formation is a pathogenetic step in gamma-diketone neuropathy. AB - Previous studies from this laboratory have demonstrated that the addition of methyl groups at the 3 and 4 positions of the 2,5-hexanedione (2,5-HD) molecule results both in more rapid pyrrole formation and in enhanced neurotoxicity. In order to define more clearly the relationship between rates of pyrrole formation and neurotoxicity, the dl and meso diastereomers of 3,4-dimethyl-2,5-hexanedione (DMHD), 3,4-diethyl-2,5-hexanedione (DEHD), and 3,4-diisopropyl-2,5-hexanedione (DiPHD) were synthesized and purified. The rates of pyrrole formation were compared with that of unsubstituted 2,5-HD, and rates of in vitro crosslinking were determined. Each of the compounds was administered to rats to determine relative neurotoxicity. Hindlimb paralysis was reached after a total administered dose of 1.6 mmol/kg of dl-DMHD, while 5.9 mmol/kg of meso-DMHD was required. Paralysis was not achieved with either diastereomer of DEHD or DiPHD, although both produced systemic toxicity. Histologic sections of spinal cords and anterior roots from rats treated with DMHD revealed large neurofilament-filled axonal swellings, while more distal sections contained axons undergoing Wallerian-type degeneration. Neither axonal swellings nor Wallerian-type degeneration were seen in sections from spinal cord or peripheral nerve of rats treated with DEHD or DiPHD. The rates of pyrrole formation were in the order dl-DMHD greater than meso DMHD greater than 2,5-HD greater than dl-DEHD greater than meso-DEHD greater than dl-DiPHD greater than meso-DiPHD, while in vitro crosslinking rates were in the order dl-DMHD greater than meso-DMHD greater than dl-DEHD greater than meso-DEHD greater than 2,5-HD greater than dl-DiPHD greater than meso-DiPHD. Cyclic voltammetry showed that the autoxidation of pyrroles derived from DMHD, DEHD, and DiPHD occurred more readily than that derived from 2,5-HD. In addition, we report for the first time the segregation of axoplasmic organelles in animals treated with DMHD, providing further evidence that the neurofilamentous axonopathies caused by such compounds as beta,beta'-iminodipropionitrile (IDPN), 2,5-HD and CS2 share a common underlying mechanism. The strong correlations between rates of pyrrole formation, rates of in vitro crosslinking and relative neurotoxicity are seen as evidence that pyrrole formation is a step in the pathogenetic sequence of gamma-diketone neuropathy. PMID- 3103261 TI - Differential induction of cytochrome P-450 catalyzed activities by polychlorinated biphenyls and benzo [a]pyrene in B6C3F1 mouse liver and lung. AB - The properties of some constitutive and inducible enzyme activities of liver and lung microsomes were determined in B6C3F1 mice pretreated by either intratracheal (i.t.) administration of benzo[a]pyrene (BaP) or polychlorinated biphenyl (PCBs) mixture (Aroclor 1254), or intraperitoneal (i.p.) administration with Aroclor 1254. After i.p. administration of Aroclor 1254, liver cytochrome P-450 content, aryl hydrocarbon hydroxylase (AHH), benzphetamine N-demethylase and nitroreductase activities were increased 2.8-, 2.0-, 2.2-, and 2.0-fold, respectively. Lung cytochrome P-450 content was also increased (1.9-fold) after i.p. administration of Aroclor 1254; AHH and nitroreductase activities, however, were not affected and benzphetamine N-demethylase activity was decreased. Aroclor 1254 administered i.t. did not affect liver cytochrome P-450 content. However, AHH and benzphetamine N-demethylase activities were decreased 1.4- and 1.2-fold, respectively, and nitroreductase activity was increased 1.6-fold. After i.t. administration of Aroclor 1254, lung cytochrome P-450 content and AHH activity were increased 1.4- and 2.2-fold, respectively. Benzphetamine N-demethylase activity was decreased 2.1-fold and nitroreductase activity was not affected. After i.t. administration of BaP, liver 7-ethoxyresorufin O-deethylase and nitroreductase activities were increased 2.2- and 1.5-fold, respectively, and benzphetamine N-demethylase activity was decreased 1.3-fold. Lung AHH and 7 ethoxyresorufin O-deethylase activities were increased 4.3- and 3.1-fold, respectively, and cytochrome P-450 content, benzphetamine N-demethylase and nitroreductase activities were decreased 1.4-, 1.2- and 1.3-fold, respectively, after BaP administration. These data indicate that different cytochrome P-450 isozymes induced in B6C3F1 mice are responsible for monooxygenase and nitroreductase activities, and that the route of administration of chemicals is important in the expression of cytochrome P-450 catalyzed activities. PMID- 3103262 TI - Chronic valproic acid and coantiepileptic drug therapy and incidence of increases in serum liver enzymes. AB - Results are described on the association of increased serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) activities with valproic acid (VPA) and coantiepileptic drug therapy in a group (n = 126) of randomly selected chronically medicated out-patients. The highest incidence (SGOT, 28.3%; SGPT, 26.1%) of elevations occurred in patients comedicated with VPA-phenobarbital (PB)-phenytoin (PHT) combinations, followed by those in the VPA PB group (SGOT, 19.5%; SGPT, 7.3%). No SGPT elevations were detected in any patients (n = 40) on chronic VPA monotherapy, while SGOT was marginally elevated in 20% of the cases. Considering the total sample (n = 126), SGOT activities were found to be linearly and directly correlated with VPA plasma concentration (n = 126, r = 0.228, p less than 0.01), PB concentration (n = 86, r = 0.352, p less than 0.01), PHT concentration (n = 45, r = 0.336, p less than 0.01), sum of VPA PB concentrations (n = 86, r = 0.440, p less than 0.001), and sum of VPA-PB-PHT concentrations (n = 45, r = 0.481, p less than 0.001). The corresponding correlations for SGPT activities were similar, except that no correlation was observed in the case of VPA monotherapy. Student's t tests for equality of means showed that the subgroup with abnormal enzyme activities had a significantly higher mean plasma concentration for PB, PHT, sum of VPA-PB, and sum of VPA-PB PHT when compared with normal enzyme subgroup patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103264 TI - Effect of sodium valproate on phenobarbital serum levels in children and adults. AB - The influence of sodium valproate on serum levels of phenobarbital during combination treatment was studied in 29 children and 50 adults with epilepsy. Steady-state drug levels in serum were determined immediately prior to drug administration using immunoenzymatic analysis. The serum level/dose ratio of phenobarbital increased significantly (p less than 0.001) when sodium valproate was added to the treatment. The increase had a mean value of 50.9% in adults and 112.5% in children, suggesting marked interindividual variability in the intensity of the interaction. Almost half of the patients required a decrease in the dose of phenobarbital prescribed. The interaction was more pronounced in patients with high serum levels of phenobarbital, while the dose of phenobarbital and the serum levels and dose of sodium valproate did not seem to affect the extent of the interaction. Close monitoring of the serum levels of phenobarbital is recommended during simultaneous treatment with sodium valproate. PMID- 3103263 TI - Variable free and total valproic acid concentrations in sole- and multi-drug therapy. AB - Total and free valproic acid (VPA) serum concentrations differ between patients on sole therapy (SOLE Group) and those taking multiple drugs (MULTI Group). We found significantly higher total and free VPA levels and free fractions in 25 SOLE patients than in 29 MULTI patients, both at morning predose (minimum) and postdose (maximum) testing. Results in SOLE versus MULTI patients were, respectively, as follows: total minimum 70.5 vs. 50.2 micrograms/ml (p less than 0.01); total maximum 106.8 vs. 89.5 micrograms/ml (p less than 0.05); free minimum 9.8 vs. 4.4 micrograms/ml (p less than 0.001); free maximum 18.9 vs. 12.0 micrograms/ml (p less than 0.01). The wide variation in total and free levels suggests the need to monitor VPA levels carefully. Not only does use of other drugs influence VPA kinetics, but the time since last dose also affects levels. Nonlinear binding causes large increases in free levels as total VPA concentration rises. We monitor free and total VPA at minimum and maximum along with evaluation of side effects and seizures for better interpretation of dosage requirements. PMID- 3103265 TI - "Radiochemically pure [1-14C]valproic acid"--a mixture of labeled structural isomers. AB - Ongoing studies of the disposition of valproic acid (VPA) and its glucuronide conjugate required the radiolabeled drug for greater sensitivity and tracing of oxidation metabolites. [1-14C]VPA hereinafter called LABEL (radiochemical purity greater than 98% as determined by paper and thin layer chromatography) was purchased from Amersham International, U.K. Quantitative analysis of VPA and VPA glucuronide in bile and urine samples from rats given VPA and tracer LABEL by our standard gas chromatographic assay showed gross discrepancies with the results obtained by liquid scintillation counting of the same extracts. Examination of the purity of LABEL was therefore undertaken. Equilibration of LABEL between various organic-aqueous solvent pairs was identical to that of authentic VPA. However, gas chromatographic-mass spectrometric analysis of the trimethylsilyl derivative of LABEL revealed it to be a mixture of labeled 2-methylheptanoic acid (approximately 60%), 2-ethylhexanoic acid (approximately 30%), and 2 propylpentanoic acid (i.e., VPA, 5-10%). The origin of the isomers of VPA in LABEL was logically traced to the synthetic procedure--coupling of the Grignard reagent of (an isomeric mixture of 2-, 3-, and 4-) chloroheptane(s) with [14C]carbon dioxide. This result highlights the inadequacy of the quality control procedures used and reinforces the necessity for caution in accepting the quoted purity of radiolabeled drugs. PMID- 3103266 TI - Low ionic antiglobulin tests. AB - Seven serologic procedures were studied to determine their respective value in compatibility and screening tests. All seven were significantly improved by the use of 4 volumes of serum, rather than 1, with 1 volume of red cell suspension, and a low-ionic antiglobin test (LIAGT) was distinctly superior to the other six procedures evaluated. In this test, during the incubation of serum and cells at 37 degrees for 20 minutes, ionic concentration was reduced 62 percent. However, after removal of all supernatant, the red cells were washed three times with an isotonic solution that provided 80 percent reduction in ionic concentration, and the washed cells were tested for their agglutinability with low-ionic (80% ionic reduction) anti-IgG antiglobin reagent. This modified LIAGT was usually more, and apparently never less, sensitive than a test described earlier and is expected to be associated with much less nonspecificity. The extreme sensitivity of LIAGT for many long-term frozen stored alloantiserums is a retained property of the modified test and has been associated with IgG aggregation during storage. PMID- 3103267 TI - Comparison of a commercial hexadimethrine bromide method and low-ionic-strength solution for antibody detection with special reference to anti-K. AB - The sensitivities of manual low-ionic hexadimethrine bromide (Polybrene, LIP) and low-ionic Polybrene indirect antiglobulin tests (LIPAT) were compared with those of a manual low-ionic-strength indirect antiglobulin test (LISS) by using a commercial Polybrene kit. One hundred antibodies were coded, titrated, and tested in parallel. LIP did not detect 36 antibodies: 31 anti-K, two anti-E, two anti Fya, and one anti-Jka. LIPAT did not detect seven anti-K, two anti-E, and two anti-Jka. The combination of LIP and LIPAT did not detect two anti-E that were reactive only in a two-stage enzyme test and seven anti-K that had titers of 2 or lower by LISS. LISS detected all antibodies except for the two enzyme-reactive anti-E. There were no significant differences in the titers of 63 percent of the antibodies studied. For 54 percent of the antibodies in the Kell system, LISS produced significantly higher titers; for 25 percent of antibodies in the Rh system, LIP did so. The poor sensitivity of the Polybrene kit for anti-K makes it unsuitable as a primary method for antibody screening. PMID- 3103268 TI - False-positive results with chemically modified anti-D. AB - Chemically modified anti-D typing serum is considered to combine the reliability of saline IgM anti-D with the convenience of slide and rapid tube anti-D. This has led to its wide acceptance in modern blood bank practice. False-positives are considered rare and are controlled by the ABO grouping. The extra step of an Rh control, which is necessary with IgG slide and rapid tube anti-D serums, is thus eliminated. However, this report shows that adopting this practice can be misleading and dangerous. Two cases are reviewed in which the chemically modified anti-D gave false-positive results and the ABO typing did not act as an adequate control. PMID- 3103269 TI - A heat-treated factor VIII concentrate prepared by controlled-pore glass adsorption chromatography. AB - Four years' experience with a method for preparing a high-purity, low-fibrinogen, heat-treated factor VIII concentrate is reported. The process, batch adsorption of a cryoprecipitate extract with controlled-pore glass granules, removes 77 percent of the cryoprecipitate fibrinogen, resulting in a final concentrate specific activity of 0.74 IU factor VIII per mg of protein at a yield of 194 IU factor VIII per kg of starting plasma. Heat treatment of the lyophilized concentrate for 72 hours at 60 degrees C results in less than 10 percent loss of factor VIII activity. This process does not require expensive fractionation equipment, is suitable for small-to medium-scale batch concentrate production and could be adopted by moderately well-equipped regional blood processing laboratories for the decentralized production of a high-quality, heat-treated factor VIII concentrate. PMID- 3103270 TI - Prospective-concurrent audits and medical consultation for platelet transfusions. AB - Prospective-concurrent audits and medical consultation were associated with a 56 percent decrease in the use of platelet concentrates at a tertiary care medical center. This study documents that mandatory pretransfusion review of component requests can alter hospital transfusion practices. PMID- 3103271 TI - A review of recent events related to surrogate testing of blood to prevent non-A, non-B posttransfusion hepatitis. AB - A workshop sponsored by the Food and Drug Administration was held recently during which available data were reviewed concerning surrogate testing of blood donated for transfusion in order to reduce the risks of posttransfusion non-A, non-B hepatitis. Clinical studies from which the efficacy of testing for alanine aminotransferase and antibody to hepatitis B core antigen (anti-HBc) could be predicted indicated such testing would be useful, although several studies using tests for anti-HBc developed recently questioned their effectiveness. Different approaches to establishing the cut-off values for the screening tests were presented and difficulties regarding test standardization were discussed. The legal, ethical, and medical implications for donors of surrogate screening programs in the United States also were considered. A meeting sponsored by the private sector that included representatives of the major blood banking organizations and was convened to discuss the workshop proceedings and nationwide screening of the blood supply also is summarized. PMID- 3103272 TI - Developments in isolated pancreatic islet transplantation. PMID- 3103273 TI - Promotion of incompatible allograft acceptance in rhesus monkeys given posttransplant antithymocyte globulin and donor bone marrow. I. In vivo parameters and immunohistologic evidence suggesting microchimerism. AB - This report extends previous studies demonstrating that prolonged acceptance of incompatible kidney allografts in rhesus monkeys can be achieved by a short recipient rabbit antithymocyte globulin (RATG) treatment course followed by donor bone marrow infusion on day 12 without a requirement for chronic immunosuppression. Serial studies of antilymphocyte cyctotoxic antibody in recipients' sera following RATG injections showed pan-lymphocyte-reactive antibody present until day 10 posttransplant. On days 11 and 12, pan-lymphocyte reactive antibody was no longer detectable, but cytotoxic antibody specific for mature T cells remained in recipients' sera. These findings might explain the critical time relationship between antithymocyte globulin treatment and donor bone marrow infusion, and further suggest that the tolerance-promoting cell in donor bone marrow is not a mature T cell, but rather a pre-T or a non-T cell. Finally, it was found that this treatment protocol resulted in development of lymphoid nodules in the transplanted kidney that express a CD8-positive, FcIgG receptor-positive phenotype and appear to be of donor origin. The possibility of a veto cell type of mechanism is discussed as an explanation for the promotion of allograft acceptance in this model. PMID- 3103274 TI - Depletion of T lymphocytes from human bone marrow. Use of magnetic monosized polymer microspheres coated with T-lymphocyte-specific monoclonal antibodies. AB - A new technique for depletion of T cells from bone marrow is presented. Bone marrow cells (BMC) were rosetted with magnetic monosized polystyrene microspheres coated with monoclonal antibodies (MAbs) specific for T cell CD2 and CD3 antigens. Rosetted T cells were subsequently removed from non-T cells with the aid of a magnet. This immunomagnetic separation procedure was carried out in less than 40 min and reproducibly removed T cells, leaving a maximum of 0.025% sheep red-blood-cell (SRBC) rosette-forming cells and less than 0.02% T cells as detected by a T cell limiting dilution assay. The efficacy of the depletion procedure was further shown by flow cytometry data, by effective removal of cells from a T cell line added to the BMC prior to immunomagnetic separation, and by abrogation of interleukin 2 (IL-2)-producing capacity in T-cell-depleted BMC (BMC T). The T cell depletion procedure provided a 43-74% recovery of non-T cells present in the Isopaque-Ficoll-isolated bone marrow mononuclear cell fraction and did not disturb the growth potential of stem cells, as assayed by hematopoietic stem cell assays. PMID- 3103276 TI - Frequent occurrence of monoclonal gammopathies with an imbalanced light-chain ratio following bone marrow transplantation. PMID- 3103275 TI - Specific ex-vivo depletion of human bone marrow T lymphocytes by an anti-pan-T cell (CD5) ricin A-chain immunotoxin. AB - We studied optimal conditions for ex vivo elimination of mature T cells from human bone marrow by T101 immunotoxin (T101-IT) with criteria applicable to graft versus-host disease (GVHD) prophylaxis prior to allogeneic marrow transplantation. T101-IT consisted of T101 anti-CD5 monoclonal antibody conjugated to purified ricin A-chain toxin. Marrow mononuclear cells isolated by Ficoll-Hypaque or by fractionation with soybean lectin (SBA- cells) were incubated with T101-IT at 37 degrees C with or without ammonium chloride and/or verapamil as potential enhancers of immunotoxin potency. As controls, competitive inhibition studies with unconjugated T101 or irrelevant IgG2a antibody were carried out. Residual T cells were quantified by limiting dilution in phytohemagglutinin (PHA)-interleukin 2 (IL-2) feeder-cell-containing microcultures and hematopoietic progenitors by CFU-GM assay. We demonstrated that T101-IT in the range of 1-100 nM does not affect early total cell viability; that its delayed cytotoxicity is T-cell-specific, greatly enhanced by ammonium chloride, and moderately by verapamil--which also is not synergistic with ammonium chloride; and that 10 nM X 3 fractionated doses (i.e., added at 0, 1.5, and 3 hr of incubation) in the presence of 10 mM ammonium chloride for 4 hr at pH 7.8 consistently induces 2 log T cell depletion. In addition, if the same T101-IT treatment is preceded by fractionation with soybean lectin (i.e., T101-IT treatment of SBA- marrow cells), 3 log T cell depletion is accomplished. We conclude that T101-IT is highly effective in eliminating T cells from donor grafts. However, data presented here indicate that T101-IT should be associated with additional methods, such as soybean lectin fractionation, to ensure more effective ex vivo T cell depletion and acute GVHD prevention. PMID- 3103277 TI - Clinical pancreas and islet transplantation. PMID- 3103278 TI - Internalization (but no recycling) of T cell receptor, T3 antigen, and other T cell antigens. PMID- 3103279 TI - Studies on the two-signal model for T cell activation in vivo. PMID- 3103280 TI - Influence of recombinant gamma-interferon on enhancement of major histocompatibility complex class II antigen expression and functional immunological capacities of human amniotic and chorionic villi cells. PMID- 3103281 TI - Prolongation of murine cardiac allografts following treatment of graft recipients with monoclonal anti-L3T4 and Ly-2 antibodies. PMID- 3103282 TI - Monoclonal anti-IL-2 receptor antibody in primate renal transplantation. PMID- 3103283 TI - Heart and heart-lung transplantation. PMID- 3103284 TI - Morphology and function of free lung cells following combined hetero-orthotopic heart-lung transplantation in the dog. PMID- 3103285 TI - Synergy of ALS and UV-B in prolongation of primate-to-mouse islet xenograft survival. PMID- 3103286 TI - Prolongation of rat cardiac allograft survival with arachidonic acid metabolism inhibitor. PMID- 3103287 TI - Improved maintenance of adenosine triphosphate in five-day perfused kidneys with adenine and ribose. PMID- 3103288 TI - Intralymphocytic ionized calcium evaluation in kidney allografts rejection. PMID- 3103289 TI - Pharmacodynamic assays of the immunosuppressive action of cyclosporine therapy in transplant recipients. PMID- 3103290 TI - Prolonged survival of endocrine allografts with preoperative cyclosporine A. PMID- 3103291 TI - Oral glucose tolerance and response to mixed meals in dogs bearing long-term transplanted islets of Langerhans. PMID- 3103293 TI - Effect of hybrid artificial pancreas on glucose regulation in diabetic dogs. PMID- 3103295 TI - Effect of skin grafts on pancreatic islet cell allografts in the renal subcapsular space. PMID- 3103294 TI - The use of OKT3 to treat steroid-resistant renal allograft rejection in patients receiving cyclosporine. PMID- 3103296 TI - Analysis of donor criteria for the prediction of outcome in clinical liver transplantation. AB - The results of 219 orthotopic human liver transplants performed during 1985 at the University of Pittsburgh were reviewed to determine whether donor parameters could be used to predict the quality of early graft function. Multivariate discriminant analysis demonstrated that traditional parameters of donor assessment are unreliable predictors of poor graft function. Furthermore, 56% of the donors considered poor by conservative selection criteria produced livers with good early posttransplant function. Survival of recipients of primary allografts from donors rated poor was no different than survival of recipients of allografts from donors rated good. PMID- 3103297 TI - OKT3 in the reversal of acute hepatic allograft rejection. AB - OKT3 was an effective immunosuppressant agent in patients with acute cell mediated allograft rejection that had not responded to initial steroid therapy. OKT3 was also valuable for treating patients with early hepatic graft dysfunction caused by other factors than rejection. In such recipients, the doses of CyA can be greatly reduced, allowing recovery of frequently damaged kidneys while maintaining effective immunosuppression. PMID- 3103298 TI - Acute rejection of the heart-lung allograft and methods of its detection. PMID- 3103299 TI - [Holter monitoring in examination of falls and vertigo in elderly patients. A 3 1/2-year study in a department for long-term care]. PMID- 3103300 TI - [Listeria monocytogenes as the cause of abortion in the 2d trimester]. PMID- 3103301 TI - Antineoplastic drug cytotoxicity in a human bladder cancer cell line: implications for intravesical chemotherapy. AB - The clonogenic survival of MGH-U1 human bladder carcinoma cells treated with melphalan, cisplatin, mitomycin-C, adriamycin, vincristine and 5-fluorouracil was measured to determine the relative contribution of drug concentration and duration of exposure to cytotoxicity and to measure the relative cytotoxic effects of these agents used in intravesical chemotherapy. The survival curves were plotted as a function of log (C X T) and were fitted using a linear least squares analysis. The survival was the same for any given C X T whether this was determined by varying concentration or by varying the duration of exposure in the cases of melphalan, cisplatin, adriamycin, mitomycin-C and 5-fluorouracil. However, duration of exposure was more important than was drug concentration in the case of vincristine cytotoxicity. By utilizing the slope of the log (survival fraction) as a function of log (C X T), the relative cytotoxicity of each agent was determined. Mitomycin C, melphalan, adriamycin and cisplatin had comparable activity in this cell line, whereas vincristine and 5-fluorouracil demonstrated much lower cytotoxicity. We conclude that: mitomycin-C, adriamycin and melphalan were the agents with the greatest cytotoxic efficacy; determination of survival as a function of C X T can be used to separate the relative importance of concentration and of duration of exposure. the cytotoxicity of 5/6 drugs studied was equal when the C X T was kept constant but concentration and exposure times were varied. PMID- 3103302 TI - Intravesical chemotherapy: combination with Tween 80 increases cytotoxicity in vitro. AB - Tween 80 was shown to enhance significantly the cytotoxic activities of the four drugs (adriamycin, epodyl, mitomycin-c, thiotepa) most frequently administered intravesically to treat superficial bladder cancer. The colony forming ability of a human bladder cancer cell line, RT112, was measured following a 1 h exposure to each of the four drugs both alone and in combination with 0.1% and 0.3% Tween 80. Cell survival was not reduced by 0.1% Tween 80 alone. We conclude that the combination of Tween 80 with these drugs might increase the therapeutic index of intravesical chemotherapy. PMID- 3103304 TI - Urethral diverticulectomy in females. PMID- 3103303 TI - Short-term perfusion and "equilibration" of canine kidneys with protective solutions. AB - Kidneys were perfused either with Euro-Collins-solution or with HTK-solution of Bretschneider. The perfusion pressure as well as the perfusion flow were measured during a six-minute perfusion. The perfusion resistance was higher in Euro Collins-kidneys than during HTK-perfusion. The venous outflow of the kidney as well as the ureteral outflow was measured during each minute of the perfusion and has analysed for osmolality, and for sodium and potassium concentrations. In Euro Collins-kidneys a complete "equilibration" of the extracellular space was not achieved, while during HTK-perfusion concentrations in the venous as in the tubular outflow, similar to those in the HTK-solution itself, could be reached. At the end of the different perfusions, tissue was analysed for biochemical parameters such as ATP, ADP, AMP and lactate as well as for morphological features. Lactate had increased and ATP had decreased during perfusion with Euro Collins-solution, while ATP had not changed and lactate had decreased during perfusion with HTK-solution. Normal glomerular, tubular and dilated vascular structures can be seen after HTK-perfusion, while a glomerular and vascular contraction takes place during Euro-Collins-perfusion. PMID- 3103305 TI - [Rational parenteral feeding in acute pancreatitis]. AB - The efficiency of amino acid drugs Polyamine and Amikin as means of nutrition in treatment of acute pancreatitis are not inferior to the preparation Alvezin "New" (GDR), the degree of nitrogen retention being even superior. PMID- 3103306 TI - [Causes of fatal outcomes in acute pancreatitis]. AB - An analysis of case histories of 142 patients dead from acute pancreatitis has been made. The most frequent cause of death at early terms was the syndrome of endogenous intoxication and bleeding from upper portions of the gastro-intestinal tract. Death at later terms was usually caused by pyo-septic complications and arrosive bleedings. It was established that in the recent years acute pancreatitis made its appearance against the background of chronic inflammatory alterations in the pancreas. PMID- 3103307 TI - [Diverticulum of the duodenum simulating cancer of the stomach]. PMID- 3103308 TI - [Interaction between copper and zinc in sheep parenterally treated with zinc oxide]. AB - Changes in copper and zinc concentrations in the blood serum of sheep were studied in clinical conditions for sixty days in relation to the intramuscular application of zinc oxide at a dose of 10 mg Zn per kg liveweight; zinc oxide was administered in a developmental preparation. Serum concentrations of zinc started increasing significantly the eighth day after administration (p less than 0.01), the maximum values were found out on the twelfth day (21.19 +/- 3.89 mumol X l 1). Significantly higher concentrations of zinc in the blood serum of test sheep were observed as soon as on the eighth day (p less than 0.01), in comparison with the untreated group, and they persisted till the end of investigation (p less than 0.01). Simultaneously with the changes in serum zinc concentrations, copper metabolism was influenced when the statistically higher values of copper concentrations in the blood serum of the test group were recorded the eighth and twelfth days (p less than 0.01), in comparison with the control animals. In the remaining period, serum copper concentrations did not show any mathematical dependence and the equalization to the original values in the treated group occurred at the end of the experiment. The above-mentioned results from the sheep treated with zinc oxide refer to a possibility of influencing mutually the copper and zinc metabolism also parenterally; this could be utilized during the treatment of secondary deficiencies, or toxicosis. PMID- 3103309 TI - [Ultrastructure of the surface sculpture of the nematodes Thelazia gulosa and Thelazia rhodesi]. AB - An electron-microscope study of the cuticle of two thelazia species revealed very interesting architectonics of the sculpture of the body surface of these nematodes. The surface layer of the cuticle is crosswise and lengthwise ridged. While certain uniformity of the shape and distribution of the surface structures can be seen in Thelazia gulosa, the case is contrary in Thelazia rhodesi. The ridges and projections of the cuticle have different structure and incidence in particular thirds of the nematode body. This unusually formed structure of body surface, which is found in thelazia, complies with the fixation and locomotion of these nematodes at the exacting place of their parasitizing--in the host's eye. PMID- 3103310 TI - [Study of the submicroscopic structure of striated muscles in Japanese quail under conditions of stress]. AB - An electronmicroscopic study of striated muscles was made in Japanese quail stressed by hypokinesis. During 15-day hypokinesis influencing m. gastrocnemius, small pale vacuoles were found out on some mitochondria. The process of alterations went on, and in the 15-day hypokinetic animals, alterations in myofibrils were observed besides the alterations in mitochondria. They manifested themselves by indistinct lines of actin and myosin fibers and by an uneven course of Z-lines. The alterations of m. gastrocnemius mitochondria in Japanese quail during hypokinesis were probably caused by energy insufficiency and subsequent hydration of the organella. Nearly all components of the muscular tissue were impaired by the 30-day hypokinesis. PMID- 3103311 TI - [Clinical and biochemical response in the prevention of nutritional myodystrophy in heifers]. AB - Clinical and biochemical responses were studied after taking the measures to prevent nutrition muscular dystrophy in young cattle in the given ecological conditions. Analyzing the biological material (blood, hair, feed, soil), we found the sufficiently high saturation of heifer organisms with the microelement selenium and on the contrary, vitamin E deficiency. Sensitive indicators of the break-down of muscular tissue were the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and mainly creatinine kinase (CPK): the activities of these enzymes increased significantly after the heifers had been driven to pasture. The stay of animals in the run to get them used to the physical load before going to the pasture was not found to be a sufficient measure to prevent muscular nutrition myodystrophy if the animals had not been administered vitamin E and selenium supplements. Of the one hundred heifers we examined, seven animals began to show the signs of nutrition muscular dystrophy; none of these animals had been administered vitamin E and selenium supplements. PMID- 3103312 TI - [Phagocytosis in calves and its dynamics after experimental treatment]. AB - We evaluated the phagocytic capacity of blood neutrophils and monocytes in calves after nonspecific stimulations of the organisms by colloidal charcoal and concentrated blood derivative administered alone, or enriched by immunomodulator (levamizol). Each of the above-mentioned preparations could be characterized by a specific response of the organism with respect to the phagocytic capacity. After administration of colloidal charcoal, both the phagocytic activity (percent of phagocytizing cells) and the particle-ingesting ability, i.e. phagocytic index, which showed two-phase changes in relation to the administration, were simulated. An increase in the phagocytic index was retained until the end of observation (four weeks), but the phagocytic activity (percent of phagocytizing cells) dropped to the level before administration as soon as in 24 hours. The phagocytic activity was also positively stimulated by the concentrated blood derivative administered alone, and the particle-ingesting ability was not influenced very much. The concentrated blood derivative with immunomodulator could be characterized by a fast increase in the phagocytic activity, accompanied by a successive short-time rise of the phagocytic index. A joint feature of all three preparations was a simultaneous increase in the percent of potential phagocytes and in the values of phagocytic activity. In none of the cases was, however, the increase in phagocytic activity accompanied by a rise in the phagocytic index. PMID- 3103313 TI - Coagulation defects of aflatoxin intoxicated rabbits. AB - Twelve New Zealand white rabbits were intoxicated with aflatoxin B1. Most rabbits developed a coagulation defect near the time of death. Immediately prior to death there were significant decreases in factors V, VII, and VIII coagulant activities and fibrinogen concentration without a change in plasma fibrin(ogen) degradation product concentration, platelet number, and detectable plasma fibrin monomers. Microscopic evidence of disseminated intravascular coagulation was present in one rabbit with marked, diffuse hepatic necrosis. Terminal serum albumin concentration was significantly correlated to plasma factors V and VII activities and fibrinogen concentration. The coagulation defect of aflatoxicosis is primarily due to diminished hepatic synthesis of coagulation factors except when hepatic necrosis is severe enough to initiate intravascular coagulation and consumption of coagulation factors. PMID- 3103314 TI - Effect of 2(3)-tert-butyl-4-hydroxyanisole (BHA) and 2-chloroethanol against pyrrole production and chronic toxicity of monocrotaline in chickens. AB - Pyrrolizidine alkaloids are found in numerous plant species throughout the world. Poultry losses due to feed contamination with seeds of Crotalaria species are well documented. Monocrotaline is the major toxic pyrrolizidine alkaloid of Crotalaria species. Studies in laboratory animals and chickens have shown a protective effect of 2(3)-tert-butyl-4-hydroxyanisole (BHA) from monocrotaline in both acute and chronic toxicity. 2-Chloroethanol is thought to interfere with the detoxification mechanisms of the alkaloids. Chickens were administered monocrotaline after separate groups were pretreated with BHA and 2-chloroethanol. There was an apparent deleterious effect of monocrotaline in 2-chloroethanol pretreated chickens, similar to that in non-pretreated birds, with respect to growth rates, morbidity, mortality, and hepatic histopathology. Monocrotaline pyrrole formation was measured in chickens pretreated with BHA and 2 chloroethanol by means of the Erlich reagent reaction spectrophotometric assay. There was a significant difference in pyrrole production between the treatment groups. The 2-chloroethanol plus monocrotaline (40 mg/kg), BHA (500 mg/kg) plus monocrotaline, monocrotaline, BHA (100 mg/kg) plus monocrotaline (20 mg/kg), and BHA (500 mg/kg) plus 2-chloroethanol and monocrotaline groups had decreasing amounts of pyrrole metabolite formation respectively. PMID- 3103315 TI - Immunotoxic effects of T-2 mycotoxin on cell-mediated resistance to Listeria monocytogenes infection. AB - The effect of T-2 toxin on cell-mediated resistance to bacterial infection was evaluated in mice exposed to Listeria monocytogenes. Mice were inoculated with 4.0 X 10(5) (LD50) or 4.0 X 10(4) (nonlethal) L. monocytogenes on day 0 and treated orally on days 0, 1, 2, and 3 with 2.0, 1.0, or 0 mg/kg T-2 toxin. Toxin induced suppression of resistance was indicated by the rapid growth of Listeria in the spleen and by significant (P less than 0.005) increases in mortality due to listeriosis. Necrosis and depletion of lymphoid tissue, lymphopenia, and a marked decrease in the influx of lymphocytes and macrophages into Listeria elicited peritoneal exudates and at sites of infection in the liver and spleen occurred in the toxin treated mice. The immunotoxic effect of T-2 toxin on cell mediated resistance to listeriosis was dosage dependent and attributed to toxin induced lymphoid depletion and the failure of surviving lymphocytes and mononuclear cells to clear the host of infection. PMID- 3103316 TI - Babesia bovis--analysis and vaccination trial with the cryoprecipitable immune complex. AB - Plasma samples from cattle recovering from acute Babesia bovis infection contain cryoprecipitable immune complexes (IC). Production of bovine and rabbit antisera to IC and subsequent serological assays indicated IC contained antigens of both babesial and erythrocytic origin. Vaccination of naive cattle with IC produced low titred antibody to B. bovis but the vaccinates did not survive challenge with a heterologous strain of B. bovis. PMID- 3103317 TI - Giant fibroma of the lung. A morphological study. AB - The authors report the case of a 78-year-old male patient with an inoperable giant lung tumour diagnosed 5 years prior to death. Fine needle cytological examination at that time was interpreted as indicative of malignancy. In the following years the tumour grew very slowly without signs of infiltration or metastatic spread. On radiological examination sharp limitation of the tumour was evident. Recurrent pleural effusions occurred and the patient died from cardiorespiratory insufficiency. Autopsy revealed a giant fibroma, well vascularized but without signs of malignancy. The diagnosis was confirmed by immunohistochemical and electron microscopic examinations. PMID- 3103318 TI - The significance of argyrophilia in human breast carcinomas. AB - The significance of demonstrating argyrophilia in human breast carcinomas is a complex issue, although there is general agreement that "true" carcinoid tumours of the breast are rare. A predominantly unselected series of breast carcinomas has been investigated for evidence of argyrophilia using the Churukian Schenk method (Churukian and Schenk 1979), alpha lactalbumin and prealbumin, a marker of neuroendocrine cells. Argyrophilia has been detected in 25% of carcinomas, including all of mucinous types. However, only 4 of 68 tumours had a diffuse cytoplasmic reaction typical of that seen in neuroendocrine cells. The others showed a focal or subluminal/peripheral reaction. Those argyrophilic carcinomas with demonstrable alpha lactalbumin had this latter pattern of reactivity, although the milk protein was always detected in lesser amounts by comparison. Prealbumin was only found to varying degrees in eight tumours and the majority of these had a diffuse or focal cytoplasmic argyrophilic reaction. It would appear that in only a small number of breast carcinomas, approximately six percent, does the presence of argyrophilia probably represent neuroendocrine differentiation, whilst in others it is related to the secretory nature of the tumour cells. PMID- 3103319 TI - Ewing's sarcoma lines synthesize laminin and fibronectin. AB - Immunoelectron microscopy was employed to detect laminin and fibronectin cell surface expression on five Ewing's sarcoma lines plus a normal fibroblast line as control. Monospecific antibodies to both glycoproteins were detected on tumour cell and fibroblast layers with colloidal gold--protein A conjugates. All five tumour lines were positive for fibronectin and/or laminin, whereas the fibroblast line expressed fibronectin only, as expected. Fibronectin displayed a dense granular pattern, typically in the cell-cell and cell-matrix adhesion areas; laminin displayed a punctate pattern. 3H-leucine metabolical labelling was also used to demonstrate laminin and fibronectin synthesis. The labelled proteins released in the culture media were separated by molecular weight on SDS-PAGE and identified by immunoprecipitation with the monospecific antibodies. The results substantiated the immunoelectron microscopy data. These findings indicate that Ewing's sarcoma lines produce a complex extracellular matrix including fibronectin and laminin, in addition to the collagens described by other workers. Histogenetic classification of this tumour in terms of extracellular matrix proteins synthesis is thus more difficult than has been supposed. The same complexity must also be borne in mind when using the matrix components as an aid to Ewing's sarcoma differentiation from other childhood tumours. PMID- 3103320 TI - Interstitial collagens and ageing in human aorta. AB - Types I and III collagen were identified in four segments of human aorta using pepsin and cyanogen bromide digestion followed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Collagen is not uniformly distributed in the different segments of the arterial wall. Collagen type I is always the major collagen present. With ageing collagen type III decrease in quantity from the heart to the distal portion of the aorta. Histologically the elastic tissue is more altered in the lower abdominal section of aorta than in the arch. This study allowed a correlation between morphological observations and biochemical changes. PMID- 3103321 TI - Increased populations of endocrine cells in Crohn's ileitis. AB - Hyperplasia of nerves has been described previously in Crohn's disease. To determine whether similar alteration of the enteric endocrine system occurs, endocrine cells of the ileal epithelium were quantified in typical cases of the disease. In the ileum from patients with Crohn's disease, there was an increase in the endocrine cell population, as visualised by immunostaining of chromogranin. Quantification of endocrine cell numbers showed significant increases in both macroscopically uninvolved (i.e. histologically normal) (35.0 +/- 3.8, cells per unit length of muscularis mucosae mean +/- SEM, P less than 0.05) and involved (44.5 +/- 5.5, P less than 0.01) Crohn's disease samples, compared with normal controls (23.7 +/- 3.4). Although individual types of endocrine cell showed slight increases in Crohn's samples, only the enterochromaffin cells in abnormal bowel showed a significantly greater population (normal controls 10.5 +/- 2.3; involved Crohn's 21.3 +/- 4.4, P less than 0.05). PMID- 3103322 TI - Neuron specific enolase demonstration in the diagnosis of a solid-cystic (papillary cystic) tumour of the pancreas. AB - Immunoreactivity to neuron specific enolase (NSE) was demonstrated in a solid cystic (papillary cystic) tumour of the human pancreas, employing immunohistochemical methods. Positive staining for NSE was found with two different antisera. In addition, sodium-dodecyl-sulphate-polyacrylamide-gel electro-phoresis (SDS-PAGE) of tumour homogenate revealed a distinct band reacting with a NSE antiserum. However, we failed to detect any hormonal products or neuroendocrine granules in the tumour. Therefore the authors advise caution in using the enzyme as a differential diagnostic tool, especially in surgical pathology of epithelial pancreatic neoplasms occurring in young females. In individual cases electron microscopy will be necessary since solid-cystic tumours of the pancreas consistently show large intracytoplasmic zymogen-like granules. PMID- 3103323 TI - Epithelioid sarcoma in children and adolescents. An immunohistochemical study. AB - Six cases of epithelioid sarcoma were studied by conventional light microscopy and immunohistochemistry. The six cases account for 1.4% of the 417 cases of soft tissue sarcoma collected at the Paediatric Tumor Registry, Kiel. The average age of the five male and one female patient was 10.8 years (median: 13 years). Particular clinical findings included the location of the tumours; three were found in the pelvis, two in the head and neck, and one in the hand. Four patients are living without disease, and one patient died of disease three years after diagnosis. Histologically, four of the six tumours revealed multinucleated giant cells. Immunohistochemically using a panel of mono- and polyclonal antibodies all cases stained positively for vimentin, cytokeratin, epithelial membrane antigen (EMA), and human milk fat globulin (HMFG-2). Five cases were positive for neuron specific enolase (NSE), and three stained positively for protein S-100. A positive reaction for alpha-1-antichymotrypsin was noted in two cases. These immunohistochemical findings attest to the multidirectional differentiating capabilities of epithelioid sarcoma and support the concept of derivation from a multipotent mesenchymal stem cell. PMID- 3103324 TI - Stereology and flow-cytometry of well-differentiated follicular neoplasms of the thyroid gland. AB - A retrospective analysis of surgically resected thyroid nodules by stereology and DNA flow cytometry was performed in 15 follicular adenomas and 15 well differentiated follicular carcinomas. The criteria for diagnosis were based on the WHO classification of thyroid tumours. By area-weighted random sampling of the visual fields for light-microscopic stereology, any subjective selection bias was precluded, and each point within the embedded neoplastic tissue was given equal probability of being analyzed. 150-250 tumour cell nucleus (TCN) profiles were studied per case by a semiautomatic image analyzing system. Flow cytometric analyses included measurement of the DNA-index, and the percentages of cells in S phase and in G2/M-phase. Adenomas and carcinomas did not differ in stereological estimates related to TCN size. As examination of the stereological techniques by nested analysis of variance showed that this result cannot be ascribed to inaccurate methods, it follows that determination of TCN size is not a useful tool for the diagnosis of malignancy in well-differentiated thyroid tumours. Both groups included similar proportions of diploid and aneuploid neoplasms. In the carcinoma group the percentage of tumour cells in the G2/M-phase was more than twice as high than in the adenoma group (P less than 0.01). The ratio of short to long TCN profile axis was significantly smaller, and the coefficient of variation of TCN profile area was significantly higher in carcinomas than in adenomas. These findings are consistent with more unequiaxed TCN and higher anisokaryosis in the malignant tumours. Despite the significant differences, however, overlap of data from individual cases precludes the use of these estimates as diagnostic criteria. Pooling of the follicular tumours and dichotomizing the sample by the DNA-index showed that mean TCN profile area is increased and surface-to-volume ratio of TCN is decreased in aneuploid as compared to diploid tumours. This finding indicates that aneuploidy is associated with an increase of TCN size. PMID- 3103325 TI - Evidence for neoplastic cell differentiation in mediastinal T lymphoblastic lymphoma. AB - Immunostaining of frozen sections from a mediastinal T lymphoblastic lymphoma (T LL) revealed the existence of two neoplastic cell populations characterized by different degrees of maturation. Several large nodules of 3A1+/T11+/T9+ T6-/T4 /T8-/T3- lymphoid cells, resembling normal early thymocytes, were surrounded by 3A1+/T11+/T9+/T6+/T4+/T8+/T3- cells resembling normal cortical thymocytes. The junctional area between early and cortical lymphocytes was occupied by numerous Leu-M3+/PAM-1+/DR+ reticular macrophages which were also characterized by J5 reactivity. Cytokeratin+/keratin+ epithelial cells were absent. Immunostaining of paraffin sections and of cytocentrifuge smears obtained from tumour cell suspensions revealed that a consistent percentage (8%) of neoplastic lymphoblasts were S-100+. Our findings are consistent with a cortical T-LL presenting areas of dedifferentiated cells or, alternatively, with an early T-LL whose cells were able to differentiate into cortical thymocytes, perhaps through the interaction with a specialized subset of J5+ macrophages. PMID- 3103326 TI - Argyrophil cells in normal endometrial glands. AB - Normal endometrium from one hundred normal cases were examined histologically, using sections stained with the Grimelius method. Endocrine cells were demonstrated in 4 cases. Immunohistochemically, these cells were positive for anti-serotonin and anti-somatostatin antisera. Argyrophil granules were also observed in supranuclear or subnuclear regions of glandular cells in 17 cases, and argyrophilia was present in the apical region including the brush borders or microvilli of glandular cells in 6 cases. In these latter 23 cases argyrophilia seemed to be nonspecific, having no relation to endocrine type secretory granules, judging from the electronmicroscopic observations on the silver impregnated sections. The presence of endocrine cells and the pattern of argyrophilia in glandular cells were similar to those found previously in endometrial glandular adenocarcinomas with argyrophil cells. This is the first report on the occurrence of endocrine cells in normal endometrial glands. PMID- 3103327 TI - Ultrastructural study of poorly differentiated medullary carcinoma of the thyroid. AB - Five cases of sporadic medullary carcinoma of the thyroid (MTC) with rapidly progressive disease were studied ultrastructurally. The tumour cells had poorly differentiated C cell characteristics. They exhibited smaller secretory granules in their narrow cytoplasm. Morphometric analysis disclosed that the average diameter of the secretory granules of the cases with a poor prognosis was 173.0 nm in comparison with 254.2 nm of well differentiated cases. The granules were fewer in the poor prognostic group (1.31/mu 2) than the well differentiated group (2.75/mu 2). Increased free ribosomes and polysomes were noted in the cytoplasm and dispersed chromatin in the nuclei. These cases should be therefore classified as poorly differentiated MTC rather than atypical or anaplastic MTC. PMID- 3103328 TI - Hepatocellular calcification. AB - Autopsy of a twenty year old girl dying from complications of renal and cardiac failure demonstrated severe hepatocellular calcification, a rare finding. The pathogenesis is thought to be a combination of dystrophic calcification caused by severe centrilobular necrosis and metastatic calcification due to secondary hyperparathyroidism. PMID- 3103329 TI - Hantaan virus M RNA: coding strategy, nucleotide sequence, and gene order. AB - The M genome segment of Hantaan virus was molecularly cloned and the nucleotide sequence of cDNA was determined. The virion RNA is 3616 bases long with 3'- and 5'-terminal nucleotide sequences complementary for 18 bases. A single long open reading frame in the viral complementary-sense RNA had the potential to encode 1135 amino acids or a polypeptide of 126,000 Da. Amino-terminal sequences of isolated G1 and G2 envelope glycoproteins were determined, revealing a gene order with respect to message sense RNA of 5'-G1-G2-3'. Mature G1 begins 18 amino acids beyond the first AUG of the open reading frame, preceded by a short, hydrophobic leader sequence. G2 begins at the 649th amino acid of the open reading frame and also follows a hydrophobic sequence. Carboxy termini of G1 and G2 were localized and gene order was verified by immune precipitation of Hantaan proteins with antisera to synthetic peptides generated by using amino acid sequences derived from the cDNA sequence. The antipeptide sera were also reactive by immunoblotting with SDS-denatured G1 and G2. Molecular weights of 64,000 and 53,700 were calculated for the G1 and G2 glycoproteins, respectively, from their predicted amino acid sequences. Five potential asparagine-linked glycosylation sites were contained within the G1 amino acid sequence and two within the G2 sequence. These data are consistent with our previous estimates of the molecular weights and extent of glycosylation of the Hantaan envelope glycoproteins. PMID- 3103330 TI - Susceptibility to infection by the human immunodeficiency virus (HIV) correlates with T4 expression in a parental monocytoid cell line and its subclones. AB - The monocytoid tumor cell line U-937 and five derived subclones were infected with the HTLV-IIIB isolate of the human immunodeficiency virus (HIV). Susceptibility to infection and sensitivity to the cytopathic effects correlated with the expression of the T4 antigen on the cell surface. On the basis of these characteristics the lines could be divided into three groups. Less than 10% T4 positive cells were present in the parental line and clone 4; hence productive infection could only be established after a long latency or with a high virus inoculum. These lines showed no or only marginal cytopathic effect. Clone 16 contained more than 95% T4 positive cells and was the most sensitive line to infection with HTLV-IIIB and its cytopathic effect. Cell death was so extensive following infection that no continuous virus producer line could ever be established from clone 16 cells. Cultures with intermediate T4 expression (50-70% T4+ cells) also had intermediate susceptibility to virus infection. Cytopathic changes, even if pronounced, could be overcome in the infected cultures by the addition of uninfected cells and, in each case, a producer line could be established. HTLV-IIIB infection of clone 16 cells could be blocked by preincubation with monoclonal anti-T4 antibodies indicating a close similarity between the HTLV-IIIB receptor on T4 positive T cells and monocytoid cells. The results thus show that T4 positive monocytoid cells can function as target cells for the HIV. PMID- 3103331 TI - [Energy expenditure in patients receiving parenteral feeding in the early postoperative period after surgical interventions on the large intestine]. AB - Indirect calorimetry was used to study the basal metabolism and energy expenditure at rest in 31 patients aged 20-80 years, on day 2 after surgery on the large intestine. It was found that the basal metabolism was increased by 13% in 64.5% of the patients (group 1) and decreased by the same value in the rest patients (group 2). The fluctuation range of energy expenditure in some patients of group 1 was from 1000 to 3400 kcal, in those of group 2, from 500 to 2000 kcal. The respiratory guotient in both groups was about 0.7. The direct measurement of energy expenditure at the early postoperational period would aid in proper rationing energy components in the total volume of the parenteral nutrition of operated on patients. PMID- 3103332 TI - [Absorption and the immune response to ovalbumin administered by various methods in the dogs]. AB - Absorption and immune response to ovalbumin (OA) were studied in chronic experiments on dogs after intraenteral administration (5 dogs) and feeding (3 dogs) with non-boiled hen eggs. A modified concurrent radioimmunoassay was used to estimate the blood serum content of OA antigenic structures and antibodies to them. In 7 out of 8 dogs the antigen was detected in blood already after the first intraenteral administration or feeding. It was established that absorption of OA antigenic structures was more intensive after intraenteral administration than after feeding with hen eggs. Antibodies to OA were detected in blood on day 15 in case of intraenteral administration and on day 20 when the animals were fed with eggs. The blood antibody titre to OA in dogs receiving ovalbumin by intraenteral route was 10-fold higher as compared to that in dogs fed with hen eggs. The data obtained evidence a high potential risk of the body sensitization to food protein during intraenteral food administration, as it happens, for example, in tube intraenteral feeding. PMID- 3103333 TI - [Surface architectonics and electrophoretic mobility of the peripheral blood erythrocytes in burn patients receiving parenteral feeding]. PMID- 3103334 TI - [Polymorphism of the antigens of the ABO and rhesus-factor systems]. PMID- 3103335 TI - [Production of alpha- and gamma-interferons by human central lymph cells in different pathological states]. AB - The IF-producing capacity of human lymphocytes obtained by drainage of thoracic duct of surgical patients was studied. The lymph cells incubated with the appropriate inducer produced interferon of alpha and gamma types. The level of IF production, particularly of the gamma type, was negatively influenced by the storage of lymph at +4 degrees C and recovery of the cells in ficoll-hypaque gradient. The time course of IF production was found on the whole to be similar to that in the peripheral blood lymphocytes. The level of alpha-IF synthesis was higher for blood cells, and that of gamma-IF for lymph cells. The synthesizing capacity of the thoracic duct lymphocytes decreased in the acute stage of the disease and increased during convalescence which was especially typical of gamma IF production. PMID- 3103336 TI - [Adjuvant chemotherapy in patients with radical resection of stomach cancer: 5 year results of a prospective randomized study]. AB - 102 patients with operable gastric carcinoma were randomly allocated to untreated control, polychemotherapy, chemoimmunotherapy. At a median follow-up of 5 years, chemotherapy did not improve the overall survival rate. However, in certain subgroups, patients with lymphnode metastases and intestinal tumor type showed a significant survival benefit when treated with adjuvant chemotherapy. Furthermore, we found the site of first recurrence very closely related to the type of tumor histology. Regardless of the positive effect of chemotherapy in retrospective subset-analysis, we do not generally recommend the use of polychemotherapy in operable gastric carcinoma. PMID- 3103337 TI - [Diagnostic significance of immunoradiometric serum TSH determination]. AB - TSH measurements using sensitive TSH-IRMA method makes differentiation of euthyroidism and hyperthyroidism possible without TSH stimulation after TRH. TSH basal values less than 0.1 mU/L proof pituitary TSH suppression (clinical overt and latent hyperthyroidism, thyroid hormone therapy etc.). TSH-basal values between 0.4 and 4.0 mU/L are found in euthyroidism. TSH-basal values greater than 4.0 mU/L indicate latent or manifest hypothyroidism. With basal TSH values between 0.1 and 0.4 mU/L (borderline values between euthyroidism and "relative pituitary hormone excess") a TRH-test ist still necessary as it is not possible to predict stimulated TSH values from basal TSH concentrations with adequate accuracy. TSH measurements using sensitive IRMA methods may be recommanded as a screening test of thyroid function. PMID- 3103338 TI - [Long-term experience using EHDP (ethylidene-1-hydroxy-1,1-diphosphonate) in the treatment of Paget's disease]. AB - 12 patients with symptomatic Paget's disease of bone were treated with the diphosphonate EHDP during a 6 month period and underwent a follow up of 12 months. 6 patients received a daily dose of 5 mg/kg, 6 patients a daily dose of 10 mg/kg. All patients reported a remarkable improvement of their clinical symptoms. The decline of the serum-alkaline-phosphatase level served as an objective criterium for reduced bone turn-over metabolism. After three months of treatment with the high dose of EHDP the serum level of the alkaline phosphatase was reduced to 52% of the initial value. After 6 months of therapy a similar good result was achieved with the lower dose of EHDP. The serum alkaline-phosphatase level remained low up to 12 months after cessation of therapy in both groups of patients. So far similar long periods of remission have not been achieved by calcitonin, which is considered to be the standard therapy of Paget's disease. Another advantage of EHDP over calcitonin is the oral route of application. If a fast initial effect is desired, a daily dose of 10 mg/kg of EHDP should be used over a period of 3 months instead of the usually recommended dose of 5 mg/kg. PMID- 3103339 TI - [Arteriosclerosis and chelate therapy]. AB - Based on a case history the therapeutic value of an iv-chelate therapy in arteriosclerosis is discussed. Ethylenediaminetetraacetate (EDTA) is used as a standard regime in the treatment of poisoning with heavy metals. The usefulness of EDTA in arteriosclerosis is doubtful: some authors suppose, that Ca-deposits are removed from arteriosclerotic lesions. This concept has not yet been proven by in-vivo experiments. Severe side effects such as hypocalcemia may cause the death of a patient under treatment. Therefore no real indications exist for treatment of arteriosclerosis with EDTA. PMID- 3103340 TI - Effect of flavanone on mixed-function oxidase and conjugation reactions in rats. AB - Flavanone administered to female Fischer 344 rats (1.00 mmol/kg per day for seven days) did not induce ethylmorphine demethylation, aniline hydroxylation, hexobarbital oxidation or aldrin epoxidation. Flavanone at 0.05 mmol/kg per day for seven days increased glutathione-S-transferase activity with 1,2-dichloro-4 nitrobenzene and 1,2-epoxy-3-(p-nitrophenoxy) propane as substrates. Flavanone at 0.05 mmol/kg per day for seven days increased the glucuronidation of 1-naphthol, and at 0.20 mmol/kg increased the glucuronidation of chloramphenicol. Flavanone administration did not alter sulphotransferase activity with 2-naphthol as the substrate and did not enhance glutathione-S-transferase or glucuronyltransferase activity when added in vitro. PMID- 3103341 TI - [Resorption and hormonal reaction in the perioperative phase following enteral administration of glucose]. AB - It was the aim of this study to find out whether a postoperative enteral nutrition with glucose is possible. Therefore, an intraduodenal glucose load (15 g/7.5 min.; 20% solution) was applied in 14 patients with normal weight and no metabolic disorders before and on 4 consecutive days after a medium severe abdominal operation. The results show that the resorption of the enterally applied glucose is reduced only on the first postoperative day. After the peak values have been reached, the decrease of glucose from the blood is delayed up to the second postoperative day, although during the whole testing period the insulin secretion--calculated according to the insulinogenic index - corresponds to the glucose stimulation. Thus, an early postoperative enteral nutrition with glucose seems to be possible, but the reduced absorption over a short period has to be taken into consideration. PMID- 3103342 TI - [Modification of the transplant rejection reaction by manipulation of the transplants--a new model]. PMID- 3103343 TI - [Value of long-term ECG in patients with syncope]. AB - In a prospective study 24 hour long-term ECG (LT-ECG) recordings under ambulatory conditions were performed in 126 patients with syncopes (SY) of unknown origin. LT-ECG revealed arrhythmias (AR) in 57%, whereas 43% had inconspicuous findings. One patient developed a SY during LT-ECG without any evidence for arrhythmias. In 40% of these patients AR not detected previously by other methods were discovered. In 36% AR detected by LT-ECG had to be considered as precursors of syncopes (i.e. bradycardia less than 40 b.p.m., tachycardia greater than 160 b.p.m., AV-block II/II and III, or ventricular arrhythmias Lown IV). LT-ECG increased the information about the cause of syncope in 35%, whereas in 65% LT ECG did not produce any further information. Consequently LT-ECG led in 56% to drug therapy, in 8% to PM-implantation. During a mean follow-up of 22 months 22% of patients developed again a syncopal attack and 4% died suddenly. Despite LT ECG recording an ECG-registration during a typical syncopal attack for the confirmation or exclusion of an arrhythmogenic genesis of the SY is achieved only by chance. Nevertheless further informations with regard to precursing AR can be obtained, which may lead to therapeutic consequences in some patients. Therefore, LT-ECG has to be recommended as an essential, non-invasive procedure in patients with SY of unknown origin. PMID- 3103344 TI - [rt-PA in acute myocardial infarct, randomized studies in Europe and the USA]. AB - Thrombolysis in acute myocardial infarction will only have a future if an intravenous route makes this treatment applicable in all patients and in all hospitals. The data available now indicate that rt-PA is more thrombus-specific than streptokinase (SK) and that its thrombolytic activity is higher. The frequency of severe bleedings is low. Reperfusion can be reached in a significantly higher number of patients in comparison to SK (60% vs. 36%; p less than 0.001) (TIMI trial). In the European trial perfusion was observed in 70% of the patients treated with rt-PA versus 55% in patients treated with SK. Ongoing randomised trials with rt-PA in Europe and in the U.S.A. investigate the efficacy of thrombolysis in regard to left ventricular function and mortality. These trials will also answer some unsolved questions concerning the role of PTCA after thrombolysis. Other thrombolytic agents such as pro-urokinase and acylated streptokinase-plasminogen complex are being investigated. Whether they have advantages in comparison to rt-PA is still open. PMID- 3103345 TI - [Neural tumor markers]. PMID- 3103346 TI - [Sensitivity of the pituitary gland of women with prolactin-secreting adenomas to thyroliberin and luliberin]. PMID- 3103347 TI - [Various aspects of the modifying effect of nutrition on chemical carcinogenesis]. PMID- 3103348 TI - [Spontaneous motor activity and radial-maze learning in rats neonatally treated with 6-hydroxydopamine]. AB - 6-Hydroxydopamine (6-OHDA: 35 micrograms) was intraventricularly injected twice to rat pups with desmethylimipramine pretreatment (20 mg/kg, sc) at 3 and 6 days of age in order to selectively deplete brain dopamine. At every 3 days from 7 through 31 days of age, the pups were tested for their locomotive activity in the open-field. The locomotive activity was measured by two different methods (counting the number of sections traversed and time-sampling behavioral items such as pivoting, creeping and walking). The results showed that significant increases in the activities by the both methods were produced by the treatment of 6-OHDA throughout the observation days. From 80 days of age the animals were trained 1 trial per day on radial 8-arm maze learning. Rats treated with 6-OHDA took significantly more trials to attain the learning criterion (at least 7 correct choices in the first 8 choices for 5 consecutive trials) as compared with the control animals. This retardation, however, was mainly derived from that of familiarization (habituation) to the apparatus in the beginning of the training. In conclusion, the neonatal treatments with 6-OHDA produced pronounced hyperactivity during the developmental period but little deficit in learning ability during the adult period. PMID- 3103349 TI - [Results of long-term D-penicillamine therapy in chronic polyarthritis]. AB - In 34 patients with severe rheumatoid arthritis the therapeutic efficacy of 600 mg/die of D-penicillamine was evaluated for five years. Patients were included in the study only if the duration of their disease exceeded 6 months (upper limit 12 months), and there was involvement of 6 or more joints and an elevated erythrocyte sedimentation rate (1 Hour values greater than or equal to 25 mm). In 9 patients (26%) a decline in the activity index could be observed, but 7 of these subjects had a deterioration of findings as assessed by x-ray. The increase of the activity index indicated no therapeutic benefit in 25 patients (74%), which could be confirmed in all subjects by x-ray. PMID- 3103350 TI - [Clinical use of Gonadorelin as a diagnostic agent in one- and two-step tests]. AB - Synthetic LH/RH Gonadorelin, produced by VEB Berlin-Chemie, was given to 11 women with a normal menstrual cycle during the middle of the follicle phase. It was proved as a very effective drug, which provoked a typical gonadotropin release. Also 10 patients with a secondary amenorrhea responded already to the first intravenous injection of 80 micrograms Gonadorelin with a peak level of gonadotropins, in particular with LH levels, after 30 to 60 minutes (delta 1 = 1 st peak level--0' level). The relative ascent of gonadotropins (delta 2 = 2nd peak level--120' level) after the second step i.v. administration of 80 micrograms Gonadorelin at a 120 minutes interval was not significantly higher than delta 1. The reaction of pituitary on LH/RH does not immediately depend on the basal level of gonadotropin values. It reflects the severity of the hypothalamic-pituitary functional disturbance. The "Gonadorelin-test" ist a good complement to the progesterone- and clomiphene-test. PMID- 3103351 TI - [Indices of phagocytosis of S and R forms of Brucella in patients with acute and chronic brucellosis caused by Brucella abortus]. AB - The characteristics of phagocytosis (phagocytic activity and phagocytic index) in patients with acute and chronic brucellosis have been studied with B. abortus S- and R-forms used as its objects. The study has revealed that higher characteristics of phagocytosis with respect to B. abortus S-forms are observed in patients with acute brucellosis, whereas in patients with chronic brucellosis taking a benign course phagocytosis is more intensive in respect of R-forms. In patients with frequent exacerbations of chronic brucellosis differences in the characteristics of phagocytosis with respect to B. abortus S- and R-forms are not statistically valid. PMID- 3103352 TI - [Morphologic changes in the structure of the human and animal brain during aging (comparative aspects)]. PMID- 3103353 TI - [Gonadal and gonadotropic function of late middle-aged men and women with sequelae of ischemic stroke]. AB - In a comparative study the authors determined peripheral blood concentrations of immunoreactive testosterone, estradiol, LH, FSH, and prolactin in 32 males and 21 females, aged 60-74 years, with consequences of ischemic stroke, and in clinically normal elderly subjects. A control group was composed of healthy young people aged 20 to 35 years. It was found that in males and females with a history of stroke secretory insufficiency of the gonads and changes in the gonadotropic function of the pituitary expressed in a relative redistribution of gonadotropin fractions were significantly more pronounced than in normal age-matched subjects. The patients of both sexes exhibited a considerable elevation of blood prolactin levels. Hyperprolactinemia may either follow stroke since the latter impairs the hypothalamic regulation of prolactin secretion or precede it contributing to the development of a metabolic background conducive to the development of cerebral atherosclerosis. PMID- 3103354 TI - [Cercarian chaetotaxy of Schistosoma mansoni from naturally infected Biomphalaria tenagophila]. PMID- 3103355 TI - [Comparison of the chaetotaxy between 2 groups of cercariae, from a human strain of Schistosoma mansoni after first passage through 2 species of congeneric snails]. PMID- 3103356 TI - Presence of bridging structures in atrial desmosomes. PMID- 3103357 TI - Distribution pattern of concanavalin A on carcinoma cells, histiocytes and mesothelial cells from effusions. AB - Fixed and unfixed cancer cells, mesothelial cells and histiocytes were exposed to fluorescein-labeled concanavalin A (ConA-FITC). Cancer cells, whether fixed or unfixed, showed a similar pattern of fluorescence, as a continuous layer over the whole periphery of the cell. This pattern of ConA-FITC distribution was also obtained on fixed mesothelial cells and fixed histiocytes. Redistribution of ConA FITC in form of "caps" and "patches" was recorded on unfixed mesothelial cells and unfixed histiocytes. Of the three cell types studied, only the histiocytes were lysed by the incubation with ConA-FITC. PMID- 3103358 TI - Metabolism of 5-S-glutathionyldopa. AB - 5-S-Glutathionyldopa is oxidized at incubation with tyrosinase and dopa producing a black pigment. The reaction proceeds with the formation of two chromophores with absorption spectra similar to those of dopachrome and melanochrome, respectively. Zn2+ catalyses the formation of the melanochrome-like compound. The oxidation of 5-S-glutathionyldopa by dopaquinone, formed by the action of human tyrosinase and mushroom tyrosinase, is considerably slower than that of 5-S cysteinyldopa. The higher oxidation potential of 5-S-glutathionyldopa, and/or the greater number of dopaquinone molecules necessary for pigment formation from 5-S glutathionyldopa and/or the formation of tyrosinase-inhibiting products from 5-S glutathionyldopa can explain the slower oxidation of this compound. The oxidative pathways suggested for 5-S-glutathionyldopa by the present findings may be relevant both in the melanocyte and in non-specific oxidation of cathechols occurring in other cells. PMID- 3103359 TI - Studies of the luteinization process in the rat: follicular and luteal adenylate cyclase responsiveness to catecholamines. AB - The subject of the study was the development of follicular and luteal catecholamine responsiveness during the periovulatory period. Follicles and corpora lutea and granulosa cells were obtained from the PMSG ovulatory model and adenylate cyclase activity measured in membrane fractions. In the earlier part of the follicular phase (48 h and 26 h before ovulation) no response to noradrenalin on follicular and granulosa cell adenylate cyclase activity was seen. A small but significant response to noradrenalin was observed from 18 h before until 3 h after ovulation. The response to noradrenalin on luteal adenylate cyclase activity increased markedly with time and reached a maximum 39-57 h after ovulation. After this time the luteal response to noradrenalin decreased with luteal age. The effect of LH was less than that of noradrenalin during the early luteal phase, and in contrast to noradrenalin, increased with luteal age. The combined effects of LH and noradrenalin were not additive. In order to test whether gonadotropins could induce a noradrenalin response, injections of LH and FSH were given to the animals two days before ovulation. LH, but not FSH, induced a small but significant response to noradrenalin 16 h later. The present investigation has shown that ovarian responsiveness to catecholamines appears in preovulatory follicles followed by a marked increase in luteal catecholamine responsiveness. This development could at least partly occur under the influence of LH. PMID- 3103360 TI - Cimetidine-induced prolactin release in rats. The effect of sex and gonadal steroids. AB - The cimetidine-induced plasma Prl response was examined in rats of both sexes. First, 10 week old intact adult males and females (dioestrous) were compared. There was no significant difference in the Prl response to cimetidine between the two groups, despite the fact that in adult females the anterior pituitary Prl content was 4 times greater than in males. Second, the effect of gonadal state in adult age on the Prl response to cimetidine was examined in both sexes. In male rats, gonadectomy at the age of 6 weeks significantly reduced the plasma Prl response as well as the pituitary Prl content, both of which were sufficiently restored by testosterone replacement. However, in females, neither gonadectomy at the age of 6 weeks nor subsequent oestradiol replacement affected the Prl response to cimetidine, despite the fact that gonadectomy significantly reduced and oestradiol treatment significantly enhanced the pituitary Prl content. Third, possible permanent effects of the postnatal gonadal milieu on the cimetidine induced Prl response and the pituitary Prl content were examined in both sexes by castration at varying postnatal ages. The ratio of plasma Prl response to pituitary Prl content was similar in all castrated males. In females, however, the ratio decreased with increasing castration age. In conclusion, the mechanism of cimetidine-induced Prl release is less sex-dependent than are the mechanisms of Prl release by other Prl secretagogues. First, this may be due to a minor role of oestrogen in females in determining the Prl response to cimetidine. Second, the postnatal ovarian secretions may exert a permanent inhibition of the development of the cimetidine-mobilized anterior pituitary Prl pool. PMID- 3103361 TI - LRH agonist buserelin as a post-partum contraceptive: lack of biological activity of buserelin in breast milk. AB - To evaluate the possibility of using the LRH agonist buserelin as a contraceptive for lactating women we have investigated the passage of buserelin into breast milk and explored possible biological activity in the infant. Eleven mothers received 600 micrograms buserelin by nasal spray. Buserelin was measured by radioimmunoassay in the breast milk of these mothers, and values ranged from undetectable levels (less than 15 pg/ml) to 8800 pg/ml. The maximum amount of buserelin that an infant could ingest during an average feed would be 1-2 micrograms. In adult men ingestion of 600 micrograms buserelin dissolved in cows milk was without biological effect upon both serum and urinary levels of luteinizing hormone. There was no change in the levels of LH found in the urine of infants fed by women who had received 600 micrograms buserelin by nasal spray. We conclude that the small amount of buserelin passing into the breast milk of these volunteers was without biological activity when ingested by the infant. PMID- 3103362 TI - The role of gonadal steroids in feedback regulation of gonadotropin secretion at different stages of primate development. AB - The serum gonadotropin response to castration was assessed in 8 foetal, 2 neonatal, 30 juvenile, and 2 adult rhesus monkeys (M. mulatta). In the 30 castrated juvenile monkeys and 8 sham-operated controls, concentrations of oestrone, oestradiol, androstenedione, dihydrotestosterone, testosterone and 17OH progesterone were measured in 10 ml serum pools before, one month after, and one year after the surgical procedure. Castration during foetal life (83-137 days gestation) was followed within 48-72 h by a significant rise in serum FSH levels in males, but had no effect on the already high levels in females. Similarly, castration of males during the first post-natal month raised serum FSH and LH into the adult castrate range; however, after 3 months of age serum gonadotropin levels again declined to the normal juvenile range in spite of the open feedback loop. Orchiectomy of prepubertal juvenile monkeys (age 3 month-2 8/12 years) had no immediate effect on serum gonadotropins, but was followed by a delayed rise in FSH (at age 2 3/12-4 3/12 years) and LH (at age 2 7/12-4 4/12 years) to adult castrate levels. Orchiectomy of older prepubertal (by serum testosterone) or adult males resulted within a few days in a progressive and sustained rise in serum FSH and a more gradual rise in LH. Prepubertal gonadotropin regulation appeared to be sexually dimorphic, since ovariectomy in juvenile females (age 3 months-1 5/12 years) was followed by generally elevated, if somewhat erratic, serum FSH values, with a secondary rise in both FSH and LH levels at 2-2 1/12 years. In both sexes, prepubertal castration caused a significant and sustained decline in serum concentrations of oestradiol; castrated males also showed a decline in serum testosterone levels. Although prepubertal castration also caused in both sexes a slight decline in serum oestrone, and ovariectomy a decline in serum androstenedione and dihydrotestosterone, these effects were not sustained one year later, and values were not significantly different from sham-operated controls. Taken together, these data lend support to a model of primate sexual maturation in which the primary regulator of gonadotropin secretion in both sexes during the prolonged juvenile phase is central inhibition of the hypothalamic GnRH regulator. However, during foetal and neonatal life, and again following the onset of puberty, the major modulator of gonadotropin secretion becomes sex steroid-mediated feedback inhibition. PMID- 3103363 TI - Oestrogen and thyroxine-binding globulin levels in early normal pregnancy. AB - Peripheral serum levels of thyroxine-binding globulin (TBG), unconjugated and total oestrone, and unconjugated oestradiol-17 beta were measured twice in 60 cases of early normal pregnancy (gestational weeks 6-19). Although highly significant correlations between TBG and oestrogen levels were obtained in the total material, the correlations within two-week intervals of pregnancy were rather poor and mostly insignificant. Furthermore, there were no associations at all between the increase rates of TBG and those of the oestrogens, either within two-week intervals or in the total material. The findings do not support the common concept of continuously rising oestrogen stimulation as the main factor affecting the TBG synthesis during pregnancy. PMID- 3103364 TI - In vitro and in vivo TSH releasing activity of two new analogues of TRH. AB - The TSH releasing activity of two new analogues of TRH 'Pyr-(N3-Im-methyl)-His Pro-NH-(n-amyl)' (I) and 'Pyr-His-Pro-(tyramine)' (II) was tested and compared with that of TRH in adult rats to test how structural modifications in the TRH molecule affect its biological activity: 1) in vitro in superfused pituitaries and 2) in vivo after ip injection, with measurement of TSH by RIA before and after addition of each secretagogue. Analogue I was found to be more potent than both TRH itself and Analogue II in stimulating TSH release: at 10 nmol/l in vitro, the ratio of induced to spontaneous release was 4.13 +/- 0.35, 2.98 +/- 0.20, and 1.19 +/- 0.17, respectively for each secretagogue, with a 50% effective dose of 6 X 10(-9) mol/l for Analogue I and 5 X 10(-8) mol/l for TRH. A similar order of potency in increasing plasma TSH (Analogue I greater than TRH greater than Analogue II) was found in vivo, as shown by dose-response curves. After a 4 day pre-treatment with TRH (2 X 100 micrograms/day) a similar TSH response to TRH and Analogue I (500 nmol/kg body weight) was observed. By contrast, the dose of Analogue II needed to obtain the same stimulatory effect on TSH release was twice as high. The biological activity of TRH appears to be more effectively increased by replacing an H atom by an amyl group in the C-terminal amide function of the proline residue of TRH than by a tyramyl group in the same residue. PMID- 3103365 TI - [Extramedullary plasmacytoma of the liver]. PMID- 3103366 TI - Continuous monitoring of oxygen tension with a transcutaneous sensor during hypotensive anesthesia. AB - Transcutaneous oxygen tension (TCPO2) is a useful noninvasive technique for monitoring arterial oxygen tension under stable circulatory conditions. This study was undertaken to determine if TCPO2 is also reliable during sodium nitroprusside-induced hypotension under general anesthesia. Arterial blood gases and TCPO2 were measured prior to inducing hypotension (baseline), at 20-min intervals during hypotension, and when systemic arterial pressure had returned to within 10% of the control (pre-hypotension) value. With induced hypotension, PaO2 and TCPO2 decreased significantly (P less than 0.05), and were well correlated by linear regression (r greater than 0.85); however, regressions were strongly dependent on the individual patient. The mean regression line for all patients as a group was given by TCPO2 = 0.69 PaO2 + 20.7 mmHg (r = 0.93, P less than 0.01); significantly different regressions were obtained for each patient (P less than 0.0001). Comparing changes in TCPO2 versus those in PaO2 (relative change from baseline values) did not substantially reduce the variability among patients. It is concluded that TCPO2 reliably reflects changes in arterial oxygen tension during controlled hypotension under general anesthesia, but that a separate calibration of TCPO2 vs. PaO2, obtained prior to inducing hypotension, may be required for each individual patient. PMID- 3103367 TI - Effects of halothane and enflurane on myocardial metabolism during postischaemic reperfusion in the rat. AB - In experiments on isolated rat heart-lung preparation, the effects of halothane and enflurane on myocardial metabolism during postischaemic reperfusion were evaluated with intramyocardial high energy phosphates, lactate and glycogen. Hearts were perfused for 10 min initially and made globally ischaemic for 8 min. Afterwards, they were reperfused for 12 min. Halothane or enflurane was administered from 5 min after the start of perfusion to the end of reperfusion. There were no significant differences in contents of high energy phosphates between control (C), halothane (H) and enflurane (E) groups (ATP: 15.50 +/- 0.87, 16.05 +/- 1.99 and 15.16 +/- 2.03 mumol/g dry wt, respectively). However, lactate levels in the hearts in Groups H and E were significantly higher than those in Group C (44.04 +/- 10.54, 40.63 +/- 10.34 vs 28.63 +/- 5.98). Slight deterioration in the myocardial oxidation-reduction state may be caused by inhalational anaesthetics when they are administered during the postischaemic reperfusion period. PMID- 3103368 TI - Circulatory effects of short-term hypercapnia during high thoracic epidural anaesthesia in elderly patients. AB - Circulatory changes and the degree of sympathetic block were evaluated in 15 elderly patients with high thoracic epidural anaesthesia (T1-T5). Bupivacaine 5-6 ml 0.5% was injected via an epidural catheter at the T3-level. The quality of the sympathetic block was determined with the Valsalva manoeuvre. Induced hypercapnia was used to quantify the degree of sympathetic block. Following thoracic epidural anaesthesia (TEA), cardiac output, stroke volume and arterial blood pressure decreased. During hypercapnia, heart rate and arterial blood pressure increased both before and after established TEA. Thus the block of the sympathetic innervation to the heart with a high TEA using 0.5% bupivacaine was not sufficient to prevent mobilization of circulatory reserves during sympathetic stimulation. The most likely explanation is considered to be the lack of neural block of the efferent nerves leading to the adrenal medulla and the peripheral vascular bed. PMID- 3103369 TI - Immunocytochemistry on the localization of 5-hydroxytryptamine in monkey and rabbit taste buds. AB - Immuno-electron microscopy with the protein A-gold method demonstrated immunoreactive gold particles against 5-hydroxytryptamine localized in cored vesicles aggregating around presynaptic terminals of the gustatory cells in monkey and rabbit taste buds. The positive reactions were also found in the intragemmal and subepithelial nerve fibers. The role of these cored vesicles in taste transduction is still uncertain but the data strongly suggest that they may participate in a serotonergic modulation of a cholinergic synaptic transmission from the gustatory cells to the nerve endings. PMID- 3103370 TI - B cell activation in multiple sclerosis. AB - A microtechnique was established for the study of the limited numbers of cells available in CSF. The method allowed for the determination of the number of immunoglobulin-secreting cells (IgSC) as well as the quantitation of immunoglobulin or specific antibody secreted into the culture medium. Dose response curves and kinetic profiles for the IgSC responses induced by pokeweed mitogen (PWM), a polyclonal B cell activator, were similar for CSF cells (CSFC) and peripheral blood mononuclear cells (PBMC). When equal numbers of unstimulated CSFC and PBMC from patients with multiple sclerosis (MS) were cultured, both the number of IgSC and the amount of secreted IgG were significantly greater in CSFC cultures. The addition of PWM resulted in the differentiation of B cells among both CSFC and PBMC, as shown by an increase of both the number of IgSC and the amount of secreted IgG. Results with cultures of unstimulated cell suspensions from MS patients suggested that CSF cells from these patients may be activated in vivo. The addition of mitomycin-C treated autologous peripheral blood mononuclear cells (PBMCM) to cultures of small numbers of CSFC or PBMC resulted in an augmentation of the number of IgSC in both, whether or not they were stimulated with PWM, and also in an increased secretion of IgG into the culture supernatants. This culture system should prove useful in functional studies when limited numbers of cells are available. PMID- 3103371 TI - Anti-neurofilament antibodies in blood of patients with neurological diseases. AB - A method has been developed to determine quantitatively the level of the anti neurofilament antibodies in the blood of patients affected with different neurological diseases. In 7 out of the 52 patients, taken as controls and in 33 out of the 208 patients affected with neurological diseases, the antibody levels were increased. The increases were greater in 43 patients with Parkinson dementia and amyotrophic lateral sclerosis who originated from Guam. On the other hand, the levels were very low in 10 patients affected with subacute sclerosing panencephalitis and in 11 cases with Chagas' disease. In 24 cases with dementia of Alzheimer type, the levels were normal. PMID- 3103372 TI - Farber's disease in two siblings, sural nerve and subcutaneous biopsies by light and electron microscopy. AB - Two siblings born from consanguineous tunisian parents are reported. They showed a severe form of Farber's disease with prominent involvement of the central and peripheral nervous system: low conduction velocity was noticed in both children. Macular cherry red spots were observed in one of them. The diagnosis for the girl investigated was confirmed by evidence of ceramidase deficiency in cultured fibroblasts. Here we report the pathological findings in the subcutaneous nodules using light and electron microscopy (one case), and in sural nerves using morphometric studies (both cases). Varying morphological aspects of intracellular inclusions, depending on the tissues involved, are described and discussed. A review of all cases reported since Farber's first paper in 1952 is given. PMID- 3103373 TI - Immunohistochemical study of chondroitin sulfate in human gliomas. AB - A polyclonal rabbit antiserum was utilized to localize chondroitin sulfate in human gliomas. Tissue sections were digested with chondroitinase ABC to create the antigenic determinant on the chondroitin sulfate proteoglycan molecule. Normal CNS tissue showed a positive immunohistochemical staining both in white and gray matter, sparing the cytoplasm of glial and neuronal cells. Differentiated astrocytomas presented the same pattern as the normal CNS. Anaplastic astrocytomas and glioblastomas showed progressive reduction of parenchymal positivity as anaplasia increased. These data suggest that chondroitin sulfate is a character expressed by differentiated CNS cells and that it is lost with dedifferentiation. Vascular structures presented positive material in the adventitia in all the oncotypes. A discontinuous positivity was observed in the basal membrane zone of the vessels. PMID- 3103374 TI - Immunohistochemistry of so called "neoplastic angioendotheliosis". AB - Three cases of "neoplastic angioendotheliosis" were examined immunohistochemically by the peroxidase-antiperoxidase method for Factor VIII related antigen and various leukocyte markers. In all three cases, the tumor cells stained positively for common leukocyte antigen. IgM, and kappa or lambda light chains were demonstrable in two cases. Stains for carcino-embryonic antigen and muramidase were negative. This indicates that the neoplastic cells in the lumen of blood vessels were of lymphoid origin. PMID- 3103375 TI - The CO2 laser in the laryngeal microsurgery. AB - 636 patients suffering from several laryngeal pathologies were treated with the CO2 laser. The results obtained confirm that this instrument is a valid alternative surgical tool, in comparison with the traditional surgery, because it allows to carry out the removal of the lesion with greater precision and more advantageously, when clinical indications are exact and surgical technique correctly performed. The results are as follows: Vocal nodules: no real advantages are offered by the CO2 laser in the treatment of these pathologies, whereas, in a small percentage of cases, the occurrence of reactive nodules or scars was noted; Cordal polyps are better removed with the traditional procedures, whereas the CO2 laser allows a more accurate excision of voluminous polyps or edemas of Reinke because of the bloodless operative field; Dyskeratoses: better functional results can be obtained using the laser. In these cases, however, an accurate preoperative evaluation is of fundamental importance to exclude any carcinomatous degeneration; Laryngeal amyloidosis is easily removed with minimal trauma and functional impairments using the laser; Laryngeal papillomatosis: the laser makes it possible to achieve complete recovery if radical excision, avoidance of accidental laryngeal damage and frequent postoperative controls are done; Laryngeal cancers: when clinical indications are correct, the main laser advantages in the treatment of T1 and T2 glottic cancers are the endoscopic removal of the lesion, avoidance of tracheotomy, shorter hospital stay and better quality of voice. Radical excision of the lesion is obtained by dissecting the tumor along the traditional cleavage plane, i.e. the inner perichondrium of the thyroid cartilage; Bilateral vocal cord paralysis: partial or total arytenoidectomy can be performed with the laser, with excellent functional results and minimal trauma and inconveniences; Laryngeal stenoses: chronic aditus edemas, vocal cord synechiae and webs are easily removed, taking care to avoid damage to the posterior commissure or to the elastic tracheal wall and performing frequent endoscopic removal of the fibrin clots in the postoperative period. Concentric stenoses and circumferential webs are firstly vaporized, then a silastic Montgomery T-tube is placed in the neocavity and left in place until re-epithelialization is completed. The insertion of a metallic tracheotomic cannula in the horizontal and descendant branches of the T-tube has been shown to be a useful precaution in order to achieve better results. PMID- 3103376 TI - Ultrastructural findings of rectal and skin biopsies in adult GM1-gangliosidosis. AB - We report the ultrastructural findings in rectal and skin biopsies in four cases with adult GM1-gangliosidosis. The rectal specimens taken under endoscopic control contained submucosal plexuses, which were easily identified on light microscopic and electron-microscopic examination. In all cases the ganglion cells in submucosal plexus contained characteristic osmiophilic lamellar inclusions, some of which were typical membranous cytoplasmic bodies, were commonly observed in the ganglion cells, Schwann's cells, vascular endothelial cells, and perithelial cells in rectal biopsy, and membrane-bound clear vacuoles were occasionally seen in the cytoplasm of rectal and cutaneous fibroblasts. However, the axons of unmyelinated nerves in both biopsies showed a normal appearance, and there was no significant change in the eccrine glands in skin biopsy. Comparing rectal and skin biopsies, the former was found to be more valuable for morphological diagnosis of this disease, and our ultrastructural examination of rectal biopsy revealed that enteric nerve cells were involved even in adult GM1 gangliosidosis with a benign course and restricted cerebral lesions. PMID- 3103377 TI - Multiple brain tumours with von Recklinghausen's disease. AB - Over the past 10 years we have experienced 33 cases of von Recklinghausen's disease, among whom 5 were cases of multiple (3 or more) brain tumours. In the past we have extirpated multiple tumours in a one-stage operation, but the results were poor. Recently, we have done multi-stage operation in two cases thought to require surgical treatment and have obtained satisfactory results. We have discussed the autopsy results of our own case of multiple neurinomas and meningiomas and have reviewed the 44 reported cases of von Recklinghausen's disease in whom the presence of three or more brain tumours had been confirmed at surgery or autopsy. PMID- 3103378 TI - [Multiple ureteral diverticula]. PMID- 3103379 TI - The role of oviducal secretions in mediating gamete fusion in the toad, Bufo bufo japonicus. AB - A fertilizing sperm of the anuran amphibians has to pass through the jelly envelopes and the vitelline envelope (VE) before making a successful fusion with the egg plasma membrane. Of these the jelly envelopes, secreted by the long pars convoluta (PC) portion of the oviduct, have long been known to be indispensable for the sperm entrance in the egg. The most recent experiments employing dejellied uterine eggs of the toad, Bufo bufo japonicus, revealed that the jelly plays its role in fertilization by its unique capacity of retaining divalent cations (Ca2+ and/or Mg2+) which are essential for a fertilizing sperm. There are other lines of evidence which implicate that the secretions of the uppermost portion of oviduct, p. recta (PR), render the VE penetrable by sperm. We show that the secretory granules (PRG) isolated from PR of ovulating Bufo females by centrifugation in Percoll possess such biological activities as an increase of fertilizability of coelomic eggs and the induction of both the acrosome reaction and a release of the VE lysin from sperm. In addition, the activities of the PRG are inhibited by trypsin inhibitors, and this trypsin-like activity is dependent on Ca2+. These results, combined with the previous immunohistochemical demonstration of the deposition of PR-substance(s) in the VE, lead us to propose that a fertilizing toad sperm is acrosome-reacted in response to the PRG substance deposited in the VE and finds a way of traversing the VE by the released lysin, both of which may be dependent on Ca2+ supplied by jelly envelopes, the product of PC. PMID- 3103380 TI - Oviducal pars recta as factor in fertilization properties and hormonal regulation in the toad Bufo arenarum. AB - In this communication I have attempted to present an overview of some contributions to the understanding of the oviduct-egg interaction in amphibians. According to data from other authors, the vitelline envelope of the newly ovulated egg constitutes a barrier for the passage of spermatozoa. Our results demonstrated that only after they have been affected by substances released by the first 1-3 cm of the oviduct (pars recta), is the envelope sensitive to spermlysins and the oocytes fertilizable. This functional change is matched by biological, physicochemical and morphological differences in the vitelline envelope. The fact that the pars recta activity is affected by the sexual cycle and that in ovariectomized females - devoid of active pars recta - the biological activity can be restored by steroid hormones, strongly suggests that the molecules involved in fertilization are synthesized and secreted during specific steps of the reproductive cycle. The pars recta-oocyte interaction probably involves more than one type of molecules, considering the observations made on the carbohydrate metabolism of coelomic eggs, which could be altered by the oviducal secretions. Several explanations for the pars recta mechanism of action have been suggested. One is a direct action on the sperm; pars recta molecules - engulfed in the vitelline envelope - would trigger the acrosome reaction. We propose the unmasking of specific vitelline envelope sites for sperm interaction. Material on the outer surface of the VE can be removed or altered by the enzymatic activity - similar to plasmin and trypsin - detected in the pars recta secretions. PMID- 3103381 TI - The receptor function of galactosyltransferase during mammalian fertilization. AB - The molecular mechanisms underlying mouse sperm binding to the egg zona pellucida are being examined. A variety of studies suggest that galactosyltransferase (GalTase) on the sperm surface at least partly mediates gamete adhesion by binding to its appropriate carbohydrate substrate in the egg zona pellucida. The first indication that GalTase serves as a sperm receptor came from a biochemical analysis of sperm bearing mutant alleles of the t-complex. t-bearing sperm, which are transmitted perferentially during fertilization relative to normal sperm, have four times the surface GalTase activity of wild-type, while eight other enzyme activities are indistinguishable between normal and t-sperm populations. Interestingly, mutant t-sperm that have lost their fertilizing superiority due to genetic recombination, no longer show elevated GalTase activity. Before sperm are capable of binding to the eggs, the GalTase active site becomes exposed on the sperm surface, due to the release of a competitive substrate. When added back to sperm/zona binding assays, this GalTase substrate inhibits binding by competing for the GalTase active site. Inhibition and/or modification of the sperm GalTase with either substrate analogues or modifier proteins, produces a parallel inhibition of sperm GalTase activity and sperm binding to the zona pellucida. The presence of the second GalTase substrate, UDPGal, causes the dissociation of sperm bound to the zona pellucida. UDPGal forces catalysis to occur, thus releasing the sperm GalTase from its zona pellucida substrate. Purified GalTase inhibits sperm/zona binding, as does galactosylation of the zona pellucida. Monospecific anti-GalTase IgG, and its Fab fragments, inhibit sperm/zona binding and GalTase catalytic activity. The sperm surface GalTase is localized by indirect immunofluorescence to the plasma membrane overlying the intact acrosome. Finally, the zona pellucida possess substrates for the sperm GalTase, and enzymatic modification of these substrates inhibits subsequent sperm binding. These studies, as well as others, all suggest that sperm GalTase serves as at least one, and possibly the principal, sperm surface receptor for binding to the zona pellucida during fertilization. Studies are in progress to identify the complementary GalTase substrate in the zona pellucida. PMID- 3103382 TI - Critical role of MAO inhibition in Parkinson's disease. PMID- 3103383 TI - MAO type B inhibitors as adjunct to L-dopa therapy. PMID- 3103384 TI - Studies on the mechanism of the dopaminergic neurotoxicity of 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine. PMID- 3103385 TI - Determination and visualization of damage to striatal dopaminergic terminals in 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism by [18F]-labeled 6-fluoro-L-dopa and positron emission tomography. PMID- 3103386 TI - Pathology of MPTP in the marmoset. PMID- 3103387 TI - Dopamine receptor function in Parkinson's disease--in vivo studies with prolactin responses. PMID- 3103388 TI - The visual system in Parkinson's disease. PMID- 3103389 TI - Parkinson's disease and long-term levodopa therapy. PMID- 3103390 TI - Long-term effect of levodopa on progression of Parkinson's disease. PMID- 3103391 TI - Fluctuation in response to chronic levodopa therapy: pathogenetic and therapeutic considerations. PMID- 3103392 TI - Long-lasting drug holiday in Parkinson's disease. PMID- 3103393 TI - Current and future approaches to therapy. PMID- 3103394 TI - Dopamine agonists as primary treatment in Parkinson's disease. PMID- 3103395 TI - Long-term effects of bromocriptine given to de novo patients with idiopathic Parkinson's disease. PMID- 3103396 TI - Long-term treatment with high-dosage bromocriptine in advanced Parkinson's disease. AB - Long-term follow-up indicated that levodopa as a replacement therapy merely improves the parkinsonian symptoms, and does so for only a limited number of years. The reason for this tachyphylaxis or declining efficacy in levodopa therapy and the increasing number and intensity of various distressing difficulties in the management of Parkinson's disease, such as dyskinesias and on off phenomena, is the main subject of many recent studies. It is still widely accepted that levodopa provides the best therapeutic tool for Parkinson's disease. Bromocriptine, an ergot derivative, is the main clinically used dopamine agonist, and it has been established as a valuable adjunct in the treatment of Parkinson's disease. Bromocriptine is most useful in patients with a declining efficacy of levodopa treatment, in patients with diurnal oscillations in motor performance, especially in patients with wearing-off phenomena, and in patients with onset and end-of-dose dyskinesias. The question of bromocriptine dosage, required to obtain an optimal benefit and a decreased rate of late adverse reactions, is quite controversial. The trend has been to lower daily dosage of bromocriptine, i.e., low doses suffice in patients with mild, early disease. Higher doses of bromocriptine seem to be required in patients with severe parkinsonian deficits. In this retrospective study of 8 years experience with high dosage of bromocriptine in levodopa response-losing parkinsonian patients, the adjunction of bromocriptine had a clear-cut but short-lasting beneficial effect on the disability scores.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103397 TI - Clinical effects of L-threo-3,4-dihydroxyphenylserine in cases of parkinsonism and pure akinesia. PMID- 3103398 TI - Positron emission tomography in Parkinson's disease: glucose and DOPA metabolism. PMID- 3103399 TI - The antigastrinic effect of a phenothiazine (LM 24056) prevents gastric secretory activity of histamine. AB - Gastric antisecretory phenothiazine LM 24056 inhibited acid and pepsin responses to feeding in dogs. Administered perorally two hours before feeding, LM 24056 reduced significantly the secretory responses to combinations of feeding either with antramine, a natural histamine derivate, or with synthetic histamine. LM 24056 reduced circulating gastrin levels (p less than 0.01 and p less than 0.001) and gastrin responses to feeding (p less than 0.01) without modifying neither circulating histamine concentrations nor histamine responses to feeding. The residual acid and pepsin secretions were closely related to gastrin reduction and endogenous or exogenous histamine, by themselves, seemed to be unable to recover the levels of secretory responses observed in response to feeding alone or in combination with antramine or histamine. These data favour a new scheme of gastric secretion regulation where gastrin would be the last step for stimulating parietal and chief cells. LM 24056 by reducing circulating gastrin prevents stimulatory effect of exogenous or feeding-released endogenous histamine. Histamine would not be thus the final common mediator for gastric secretion. PMID- 3103400 TI - LG 30435, a new bronchodilator/antiallergic agent, inhibits PAF-acether induced platelet aggregation and bronchoconstriction. AB - LG 30435 is a quaternary phenothiazinic antihistamine, endowed with bronchodilator and antiallergic activity. Since PAF-acether (PAF) is a potential mediator of asthma, LG 30435 was assayed for its ability to counteract PAF induced platelet aggregation (PA) in rabbit platelet rich plasma and bronchoconstriction (BC) in anaesthetized guinea-pigs, in comparison with other antihistamines. LG 30435 was the most potent and selective inhibitor of PAF induced PA (IC50: 66 microM), concentrations three and more than fifteen fold higher being needed to inhibit PA induced by collagen and arachidonic acid respectively. The other antihistamines, namely mepyramine, promethazine, mequitazine, thiazinamium methyl sulfate and ketotifen were less potent inhibitors of PAF-induced PA, while interfered at lower concentrations with collagen-induced PA. LG 30435 and thiazinamium, administered intravenously, inhibited dose-dependently PAF-induced BC, starting from the dose of 0.1 mumol/kg. The ED50 of LG 30435 was 0.28 mumol/kg, while the inhibition obtained with thiazinamium did not reach 50% even at 3 mumol/kg. Ketotifen and promethazine were partially active only at 3 mumol/kg, while mequitazine and mepyramine were inactive up to this dose. These results show that LG 30435 is endowed with a peculiar anti-PAF action, which may be advantageous in the treatment of asthma. PMID- 3103401 TI - How specific is the arachidonic acid-induced mouse ear oedema for lipoxygenase (LO)- and cyclooxygenase (CO)-inhibitors? PMID- 3103402 TI - [The morphological effect of noradrenaline on the visual cortex of neonatal hamsters]. PMID- 3103403 TI - [In vitro effect of native and recombinant human interferon-beta or -gamma on adenovirus infection, measured by enzyme immunoassay]. PMID- 3103404 TI - Patterns of paravertebral ossification in the prehistoric saber-toothed cat. AB - In cases of paravertebral ossification in humans, the radiographic characteristics usually lead to a specific diagnosis. Similar manifestations are sometimes described in other species. We applied knowledge of the radiographic appearance of spinal alterations in modern humans to the evaluation of 48 fused thoracic and lumbar fossilized spine specimens from the prehistoric saber-toothed cat (Smilodon californicus), in which prominent paravertebral ossification is frequently found. Inspection, conventional radiography, and, in some cases, CT and fluoride analyses were performed. The spinal alterations in the saber-toothed cat, which previously were believed to be caused primarily by trauma, showed characteristics of three major pathologic processes: trauma, diffuse idiopathic skeletal hyperostosis, and inflammatory disease of a type similar to ankylosing spondylitis. The last two categories have rarely been diagnosed in species other than humans. The results suggest that diffuse idiopathic skeletal hyperostosis and inflammatory spondyloarthropathy are diseases that occurred in prehistoric times and are not confined to the human species. PMID- 3103405 TI - "Cost-effective": a trendy, often misused term. PMID- 3103407 TI - Home parenteral therapy. PMID- 3103406 TI - Comparison of ketotifen and DSCG in treatment of food allergy in children. AB - The authors treated 17 food allergic, 2-14 year old children with chemoprophylactic drugs. The patients got either ketotifen or DSCG in random allocated for 4 weeks and thereafter a washout period of 2 weeks separated the trial period of the other drug. Oral challenge with the food was performed before the trial period and after a 4 week lasting elimination diet on the last day of each treatment. After the ketotifen therapy in 10 of the 17 patients no symptoms appeared after the challenge, whereas only 5 patients were completely protected by DSCG. However, with regards to isolated organ symptoms the two drugs were of equal value. In case of failure of one drug the other was effective with two exceptions. Symptoms of intolerance (vomiting, angioedema or abdominal cramps) occurred in 3 patients during DSCG treatment and in one of those getting ketotifen. In 3 cases of severe milk allergy (Heiner-Holland syndrome) symptom free state could be attained only if diet was supplemented by ketotifen. Symptoms of food allergy can be well prevented in children through ketotifen therapy more than by DSCG. PMID- 3103408 TI - Parkinson's disease: current view. AB - MPTP, a reverse ester of meperidine, is one of a number of "designer drugs" that have recently flooded the California drug market. Young adults who have used this drug have developed classic Parkinson's disease. The discovery that MPTP is selectively toxic to the substantia nigra has revitalized basic research on Parkinson's disease. New therapeutic strategies have been suggested, and new techniques may make it possible to detect the disease in its preclinical stage. PMID- 3103409 TI - Latent intraHisian block provoked by a seizure. PMID- 3103410 TI - Flecainide acetate for conversion of acute supraventricular tachycardia to sinus rhythm. AB - The efficacy of intravenous flecainide acetate (maximum 2 mg/kg or 150 mg given at a rate of 15 mg/min) was assessed in patients with acute supraventricular tachycardia (SVT) (within 24 hours). Fifty patients were studied, 46 with spontaneous SVT and 4 with induced SVT at electrophysiologic assessment. Conversion to sinus rhythm was achieved within 45 minutes in 76%: in 25 patients with atrial fibrillation (76% conversion), 15 with atrioventricular (AV) nodal or AV reentrant tachycardia (100% conversion) and 10 with atrial flutter or atrial reentrant tachycardia (40% conversion). Adverse effects were noted in 21 patients (42%): paresthesia in 9, drowsiness in 8, nausea in 2, accelerated ventricular rate in 5, ventricular tachycardia in 1, sinus bradycardia in 1 and hypotension in 5. Adverse effects were associated with larger dosage and atrial flutter or atrial reentrant tachycardia. Thus, flecainide acetate is effective in converting to sinus rhythm acute atrial fibrillation and AV nodal and AV reentrant tachycardias, but not atrial flutter or atrial reentrant tachycardia. PMID- 3103411 TI - Role of hypocapnic alkalosis in hyperventilation-induced coronary artery spasm in variant angina. PMID- 3103412 TI - Hemodynamic effects of intermittent transdermal nitroglycerin in chronic congestive heart failure. AB - The hemodynamic effects of intermittent and continuous treatment with transdermal nitroglycerin, 10 mg/24 hours, were compared in 10 patients with chronic congestive heart failure (CHF). Eight patients responded to initial application with more than a 20% reduction in mean pulmonary artery wedge pressure. Cardiac index increased from a control value of 2.1 +/- 0.5 to 2.4 +/- 0.6 liters/min/m2 at 2 hours (p less than 0.05) and mean pulmonary wedge pressure was reduced from 22 +/- 5 to 16 +/- 6 mm Hg (p less than 0.01). The 2 nonresponders had the largest left ventricular volumes on 2-dimensional echocardiograms. Responders were randomized to intermittent (16 hours/day) or continuous (24 hours/day) treatment for 1 month followed by a month of the alternate treatment. After 1 month of intermittent treatment, the hemodynamic response after reapplication was similar to the initial response. After another month of continuous treatment, hemodynamic values 24 hours after application were similar to initial control values and there was no change after removal and reapplication. Thus, the moderate vasodilator effect of transdermal nitroglycerin in CHF is maintained with intermittent treatment, whereas tolerance develops with continuous treatment. PMID- 3103413 TI - Transdermal nitroglycerin symposium. PMID- 3103414 TI - Energy expenditure during continuous intragastric infusion of fuel. AB - Influence of intragastric formula infusion rate on resting thermogenesis was evaluated in 24 healthy subjects. Metabolic rate (M) was measured by indirect calorimetry following an overnight fast. Subgroups then received a continuous intragastric infusion of a formula diet at three levels: submaintenance (mean +/- SEM, 1.02 +/- 0.04 times fasting M, n = 6), maintenance (1.39 +/- 0.01 times fasting M, n = 20), or supramaintenance (2.77 +/- 0.2 times fasting M, n = 14). Formula inflow was started in the evening, and intraprandial M was measured throughout the following day. Relative to fasting, submaintenance and maintenance infusions produced no detectable change in M. With supramaintenance infusion, M increased significantly (10.1%, p less than 0.05) above fasting level. Hence during continuous formula infusion a rise in M above fasting occurs only when rate of energy infusion exceeds rate of thermal energy losses. These results have implications in regard to energetic efficiency of continuous fuel infusion relative to intermittent food or formula ingestion. PMID- 3103415 TI - Modification of sweet acidophilus milk to improve utilization by lactose intolerant persons. AB - Enhanced digestion of yogurt by lactose-intolerant individuals is believed to be due to inherent beta-galactosidase (lactase) in the culture organisms that aids in the hydrolysis of ingested lactose. However, sweet acidophilus milk, which contains lactase-rich organisms, does not enhance lactose digestion. Using breath hydrogen measurements to indicate malabsorption in 14 human subjects, we compared utilization of: milk, yogurt, heated yogurt, yogurt plus lactose, heated yogurt plus lactase, sweet acidophilus milk (SAM), and SAM made with sonicated cells. Results indicate that both the reduction of lactose during fermentation and the presence of indigenous bacterial lactase are responsible for the increased ability to tolerate lactose in yogurt. Improved utilization of SAM by sonication suggests that intracellular lactase is not available during digestion and that sonication releases the lactase activity from the cells. PMID- 3103416 TI - Controlled trial of zinc supplementation during recovery from malnutrition: effects on growth and immune function. AB - To evaluate the effect of zinc on growth and immune function, 32 marasmic infants were selected on admission to the nutrition recovery center; 16 received 2 mg/kg daily of elemental zinc supplement as acetate and the remaining received a placebo. Immunity was assessed by skin-test response, T-cell blastic proliferation immunoglobulins, and infectious morbidity. Weight-for-length gain for initial 60 days in Zn-supplemented group was 9% of standard vs 3% for placebo (p less than 0.05). Energy intake was similar in both groups. Incidence of infections, especially pyoderma, was significantly higher in placebo group: 10 of 16 vs 3 of 16 in the supplemented group (p less than 0.025). Plasma Zn was correlated with number of febrile days in the prospective month (r = -0.66, p less than 0.05). The percent anergic infants decreased and serum IgA increased significantly only in Zn-supplemented group. Zinc supplementation has significant effects on weight gain and host defense mechanisms despite normal plasma levels. Zinc supplementation is recommended for optimal recovery from marasmus. PMID- 3103417 TI - Monoclonal proteins in chronic lymphocytic leukemia. AB - One hundred patients with chronic lymphocytic leukemia and a monoclonal protein in serum or urine were recognized during the period January 1971 to July 1984. IgG monoclonal proteins predominated, with the following distribution: IgG kappa 36% (0.36), IgG lambda 15% (0.15), IgM kappa 27% (0.27), IgM lambda 11% (0.11), IgA lambda 1% (0.01), and free monoclonal light chains in 10% (0.10) (kappa in 8% [0.08] and lambda in 2% [0.02]). The median concentration of M-protein was 1.0 g/dL (10 g/L) or less. The median survival (Kaplan-Meier) for the 100 patients after recognition of an M-protein was six years. The median survival was longer for patients with an IgG monoclonal protein (7.2 years) than for patients with an IgM monoclonal protein (5.2 years), although the difference was not significant. The authors found no important differences in patients with chronic lymphocytic leukemia, whether they had an IgG or an IgM monoclonal protein or a free monoclonal light chain. PMID- 3103418 TI - Unpredictable effects of K3 EDTA on mean platelet volume. AB - The changes of mean platelet volumes (MPVs) begin immediately upon exposure of the blood to K3EDTA, and differences from sample to sample are unpredictable, predominantly in the first two hours from the venipuncture. MPVs variations can range from -25 to 23.1% in respect to MPVs in untreated whole blood immediately processed. These results were obtained by a new electrooptical device (Technicon H X 1) that provides complete blood cell counting and sizing. If whole blood is collected and diluted with a reagent used by the instrument to sphere and fix red blood cells and platelets, MPVs values do not change significantly within 180 minutes from venipuncture. This approach allows one to study the true values of MPVs on Technicon H X 1. PMID- 3103419 TI - Quantitation and estimation of lymphocyte subsets in tissue sections. Comparison with flow cytometry. AB - A quantitation method for lymphocyte subsets in immunoperoxidase-stained frozen tissue sections was compared with flow cytometry in 23 cases of non-Hodgkin's lymphoma. Close correlations were obtained, demonstrating the accuracy of the technic. Weak intensity of fluorescence and fragility of the tumor cells during the fluorescence-activated cell sorter (FACS) analyses were the most likely explanations for a number of the discrepancies observed. The tissue quantitation method was precise, particularly at low values, where it was better than the FACS. A simpler and faster estimation method employing categories within 10 percentage units was also tested in this study; this method correlated as well with the FACS as the quantitation method and gave the best interobserver correlations. PMID- 3103420 TI - Flow cytometric measurement of antiplatelet antibodies. AB - A flow cytometric technic was developed to detect platelet surface-bound immunoglobulin in patients with thrombocytopenia. Elevated platelet surface IgG and/or IgM was detected in 90.9% of patients with immune thrombocytopenia purpura (ITP). False positive results occurred in 9.3% of patients with nonimmune thrombocytopenia usually associated with sepsis. False negatives occurred most frequently in adults with chronic ITP. Measurement of platelet surface immunoglobulin with this flow cytometric technic helps differentiate immune from nonimmune thrombocytopenia. PMID- 3103421 TI - Rapid identification of Staphylococcus epidermidis. AB - A panel of Minitek sugar disks, consisting of trehalose, mannitol, xylose, and sucrose, was evaluated for its ability to identify blood culture isolates of Staphylococcus epidermidis (SE). Using a heavy suspension of organism in Mueller Hinton broth, 50 microL was pipetted onto each disk in wells of a flat-bottomed microtiter tray. The tray was covered, incubated in a moist chamber in non-CO2 at 35 degrees C, and examined after 5 and 24 hours. A color change of yellow or orange was positive; no color change (red) was negative. Expected reactions for SE were as follows: negative trehalose, mannitol, and xylose; positive, sucrose. On evaluation of 227 coagulase-negative staphylococci (CNS) at 5 and 24 hours, the panel had a sensitivity of 94 and 96%, specificity of 92 and 89%, predictive value of positive tests of 97 and 96%, and predictive value of negative tests of 84 and 87%. This panel offered an inexpensive and convenient method for differentiating SE from the other CNS in five hours. PMID- 3103422 TI - Pseudo-Gaucher cells in the bone marrow of a patient with Hodgkin's disease. AB - The authors studied an 18-year-old woman with stage IIIB nodular sclerosis Hodgkin's disease whose bone marrow contained abnormal storage cells that resembled Gaucher cells by light microscopic examination ("pseudo-Gaucher" cells). Electron microscopic examination revealed that these cells differed from true Gaucher cells and resembled storage cells previously described in chronic myelogenous leukemia. The patient's peripheral blood leukocyte beta-glucosidase and serum acid phosphatase levels were elevated, ruling out the diagnosis of inherited Gaucher's disease. After treatment with six monthly cycles of systemic chemotherapy (nitrogen mustard, vincristine, procarbazine, bleomycin, doxorubicin, and prednisone), all signs of Hodgkin's disease and pseudo-Gaucher cells disappeared. Repeat leukocyte beta-glucosidase and serum acid phosphatase levels were unchanged. The present case is unique with its documentation of classical enzyme patterns for beta-glucosidase and acid phosphatase and electron microscopic features. The authors postulate that pseudo-Gaucher cells result from excessive cell breakdown with an overload of available beta-glucosidase. PMID- 3103423 TI - A study in human subjects using a new device designed to mimic the protrusive functional appliances used previously in monkeys. AB - A new appliance is described that mimics in function the protrusive jaw positioning devices used previously in monkeys. The appliance consists of maxillary and mandibular posterior biteplates separated by a sharp vertical interface perpendicular to the occlusal plane. Function of the appliance was evaluated in 35 consecutively treated patients and compared against matched controls. The patients, who ranged in age from 9 to 14 years, accepted the appliance readily and wore it 24 hours each day, even while eating. Although cephalometrics was the primary assessment tool, tomograms and/or transcranial x ray films and models were also obtained. The rate of mandibular length increase, measured from articulare, was comparable to or better than that found in monkeys using similar devices. The dentoalveolar effects were also similar to those found in monkeys, including anterior migration of the mandibular dentition and posterior movement of the maxillary dentition. The mandibular molars moved forward 4.8 mm of which 73% was determined to have come from increased anterior movement of the mandible. Subtracting normal growth, the net mandibular length increase was 2.2 mm during the 9.4-month average treatment interval. PMID- 3103424 TI - Effect of red pepper and black pepper on the stomach. AB - Spices have long been implicated as a cause of gastric mucosal injury. We assessed the effects of red and black pepper on the gastric mucosa using double blind intragastric administration of test meals containing red pepper (0.1-1.5 g) or black pepper (1.5 g) to healthy human volunteers; aspirin (655 mg) and distilled water were used as positive and negative controls, respectively. Serial gastric washes were performed after test meal administration and gastric contents were analyzed for DNA, pepsin, blood, sodium, potassium, parietal cell secretion, and nonparietal cell secretion. Both red pepper and black pepper caused significant increases in parietal secretion, pepsin secretion, and potassium loss. Gastric cell exfoliation (as reflected in DNA loss into gastric contents) was increased after red or black pepper administration; the increase after red pepper administration was dose dependent. Mucosal microbleeding was seen after spice administration and one subject had grossly visible gastric bleeding after both red pepper and black pepper administration. There were no significant differences from control between the test meals, in nonparietal volume, fractional recovery of the gastric secretions, or sodium secretion. Finally, no spice was significantly different from aspirin in any parameter studied; indeed, aspirin was comparable to the higher doses of pepper. The long-term result of daily pepper ingestion is unknown. Whether spices are detrimental, beneficial (e.g., inducing an adaptive cytoprotective response), or have no significant long term effect on the gastric mucosa is unknown and deserves further study. PMID- 3103425 TI - Incidence of inhibitors in patients with severe and moderate hemophilia A treated with factor VIII concentrates. AB - Recent data published on the prevalence of inhibitors to factor VIII in hemophiliacs on treatment show great variations, with prevalence rates ranging from 3.6 to 14.2%. We have studied the cumulative risk of inhibitor development in a cohort of 62 patients with hemophilia A. All patients were born after 1960, were natives of the Vienna area, had a factor VIII activity of less than 5%, and were treated at least once. Using the method of Cutler and Ederer, the cumulative risk of inhibitor development was found to be 24% at the age of 25 years. Most inhibitors developed between the ages of 3 and 7 years. The current prevalence of F VIII inhibitors in the group of patients studied is 17.5%. It is concluded that prevalence data underestimate the true risk of inhibitor development. PMID- 3103426 TI - Hematological aspect of Rh deficiency syndrome: a case report and a review of the literature. AB - The hematological aspects of the original case of Rhmod are reported. The subject, as in other reported cases, had a chronic hemolytic anemia characterized by stomatocytosis, reduced osmotic fragility, and abnormal autohemolysis correctable with the addition of glucose. The 51Cr red cell survival studies showed the spleen to be the preferential site of red cell destruction and splenectomy produced a dramatic improvement in red cell survival. The topic of Rh deficiency syndrome (Rhnull and Rhmod) is briefly reviewed with regard to the number of cases reported, to genetic aspects, to the hematological findings, and to the results of splenectomy. PMID- 3103427 TI - Transient response of pure red cell aplasia to anti-thymocyte globulin in a patient with T-cell chronic lymphocytic leukemia. AB - Pure red cell aplasia (PRCA) is an unusual complication of chronic lymphoproliferative disorders. A patient with T-cell chronic lymphocytic leukemia (T-CLL) had severe anemia and neutropenia. Initial in vitro studies demonstrated no evidence of T-cell suppression of erythropoiesis. Sequential bone marrow examinations demonstrated progressive red cell aplasia. In vitro studies showed that the T-cells from the patient suppressed allogeneic but not autologous BFU-E. Treatment with antithymocyte globulin (ATG) reduced circulating leukemic cells and produced a definite but transient improvement in erythropoiesis. PMID- 3103428 TI - Acquired pure red cell aplasia. PMID- 3103429 TI - Cancer mortality of capacitor manufacturing workers. AB - Experimental studies have demonstrated that certain types of commercially produced polychlorinated biphenyls (PCBs) are carcinogenic. Data in humans are still controversial. This study was undertaken in order to determine possible long-term effects, particularly cancer, in workers engaged in the manufacture of capacitors impregnated with PCBs in a plant operating since 1946. All workers employed for at least 1 week between 1946 and 1978 were admitted to the study (544 males and 1,556 females), and their mortality was examined for the period 1946-1982. Data on environmental contamination, workers' PCBs intake, and health effects (chloracne) were available, which documented the general exposure conditions in the plant. Vital status was ascertained for over 99% of the subjects, and death certificates were obtained for all deceased persons. Expected deaths were calculated using two sets of mortality rates, national and local. Among male workers, cancer deaths (14 obs.) were significantly increased as were deaths owing to cancer of the gastrointestinal (GI) tract (6 obs.). Also, mortality from hematologic neoplasms (3 obs.) and lung cancer (3 obs.) was higher than expected; however, the excess was statistically not significant. Female workers exhibited an overall mortality that was significantly increased above expectations. Cancer deaths (12 obs.) and hematologic neoplasms (4 obs.) were significantly higher than expected when compared with the local population. Interpretation of the results is limited by the small number of deaths; however, the point of interest is the consistency of these results with previous experimental and epidemiologic studies, which indicated the GI tract and lymphatic and hemopoietic tissue as the most probable target sites of the PCBs carcinogenic activity. PMID- 3103430 TI - Fiscal impact of a total nutrient admixture program at a pediatric hospital. AB - The financial impact of a total nutrient admixture (TNA) program at a 201-bed pediatric hospital was evaluated, and operational and clinical benefits of the program were identified. Data were collected over 60 days to determine the average number of patients receiving TNAs per day. Daily acquisition costs for equipment and solutions for the TNA system were subtracted from the costs that would have resulted from the delivery of TPN and fat emulsion by separate infusions. The average number of TNAs dispensed daily was multiplied by the time involved in preparing and administering the two delivery systems to determine the impact on daily personnel costs. Based on an average of 20 patients receiving TNA therapy daily, the daily costs for equipment and solutions for preparation of TNAs, as well as the daily equipment costs for TNA administration, were less than those for the administration of separate solutions. Nursing time for the administration of TNAs versus separate solutions was reduced, while pharmacy time associated with the preparation and delivery of solutions increased slightly with the TNA program. This increase was attributed to more time spent by pharmacists on compatibility screening with the TNA program. The estimated total daily cost savings with the TNA program was calculated as $515 for 20 patients. Clinical advantages of the TNA system included improving tolerance and use of fat by administration of emulsion over 24 hours; providing the patient's daily parenteral nutrient needs in a more concentrated source; and reducing the risk of touch contamination and sepsis, based on decreased manipulation of i.v. administration equipment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103431 TI - Bacterial and fungal growth after freezing or refrigerating parenteral nutrient solutions. AB - Parenteral nutrient (PN) solutions were evaluated for growth of pathogenic organisms after refrigeration or freezing and then thawing. Sixteen bags of hypertonic dextrose and amino acid solutions were divided into two series (refrigerated and frozen), inoculated with Escherichia coli. Candida albicans, Staphylococcus aureus, or Streptococcus faecalis, and exposed to freezing or refrigeration. The inoculum concentration was greater than would likely occur with patient contamination of the solution. Microbial growth in the solutions was determined after warming to room temperature and at 17 or 18 hours after reaching room temperature. There was no increased growth of C. albicans in PN solutions that were frozen versus the refrigerated samples. Counts for all of the organisms in the frozen series, immediately after freezing and then thawing, decreased or stayed the same compared with baseline counts. Growth of E. coli, Staph. aureus, and Strep. faecalis increased in the frozen samples compared with the refrigerated samples after room-temperature storage, suggesting a possible increased risk of infectious complications if contaminated solutions are left at room temperature for extended periods. Since no increased risk of microbial growth is likely in frozen versus refrigerated PN solutions that are thawed and promptly infused, batch freezing may be an effective and convenient means of preparing PN solutions for home patients. PMID- 3103432 TI - Determining total cost-effectiveness of drug therapy. PMID- 3103433 TI - Rationale for diphosphonate therapy in hypercalcemia of malignancy. Introduction. PMID- 3103434 TI - Etidronate disodium: a new therapy for hypercalcemia of malignancy. Proceedings of a symposium. PMID- 3103435 TI - Effect of etidronate disodium on the interactions between malignancy and bone. AB - This study was designed to assess the capacity of etidronate disodium (etidronate) to affect neoplastic involvement of bone by murine tumors. Using sublines of the Walker 256 carcinoma, differing in the pattern of bone involvement, etidronate was found to inhibit hypercalcemia caused by systemically acting humoral factors, to inhibit bone metastasis following inoculation of tumor cells into the abdominal aorta, and to reduce the invasion of bone adjacent to tumors. Etidronate was also found to prevent bone metastasis in syngeneic rat mammary carcinoma. Etidronate was found devoid of direct antineoplastic activity, whether administered intramuscularly, subcutaneously, or intravenously, in a series of murine tumors of different histologic varieties. At the same time, it was shown that etidronate did not modify the antineoplastic activity of any of the major chemotherapeutic agents used in these studies, nor did it demonstrate any degree of immunosuppression. The experimental models used for this study should prove useful in evaluating agents that may affect the various types of bone involvement seen in neoplastic disease. The drug's apparent lack of interference with the antineoplastic activity of standard cytotoxic agents and its lack of immunosuppressive activity suggest that it may be readily adaptable to combination chemotherapy regimens. PMID- 3103436 TI - Etidronate disodium in the management of malignancy-related hypercalcemia. AB - To evaluate the efficacy of intravenous etidronate disodium (etidronate) in controlling hypercalcemia of malignancy, 20 patients with known malignant disease and hypercalcemia were randomly assigned on a two-to-one basis to receive etidronate, 7.5 mg/kg of body weight, or placebo for three to five days. All patients received 3,000 ml of saline and 40 mg of furosemide per day. Eighteen patients completed the study. Eleven of 12 patients (92 percent) in the etidronate group attained normocalcemia, compared with two of six (33 percent) in the placebo group (p = 0.05). The etidronate group showed a greater decrease in the serum calcium level than did the placebo group (p less than 0.02). Renal calcium excretion decreased significantly in the etidronate group but not in the placebo group. Intravenous etidronate in combination with rehydration and furosemide constitutes a safe and effective alternative in the treatment of hypercalcemia of malignancy. PMID- 3103437 TI - Effects of intravenous etidronate disodium on skeletal and calcium metabolism. AB - The induction of hypercalcemia in malignant disease is almost invariably associated with increased bone resorption. However, tumor-induced changes in bone formation and renal tubular resorption of calcium are also important factors that induce hypercalcemia in some patients. In addition, alterations in calcium fluxes to and from the extracellular fluid secondary to hypercalcemia are important in maintaining or aggravating the hypercalcemic effects of increased bone resorption. These factors significantly affect the responses to treatment of hypercalcemia with inhibitors of bone resorption. This study examined the relative importance of these factors and the effects of intravenous etidronate disodium (etidronate) in neoplastic bone disease with and without hypercalcemia and in Paget's disease of bone. It is concluded that intravenous etidronate is an effective inhibitor of bone resorption, which accounts in large measure for its effects on serum calcium concentrations. These studies of etidronate in hypercalcemia suggest the response is sustained for several weeks. PMID- 3103438 TI - Intravenous disodium etidronate therapy in Paget's disease of bone and hypercalcemia of malignancy. Effects on biochemical parameters and bone histomorphometry. AB - Nineteen patients with Paget's disease and four patients with hypercalcemia of malignancy underwent hypocalcemic therapy with etidronate disodium (etidronate) administered intravenously. The dosage for patients with Paget's disease was 4.3 mg/kg/day, infused on each of seven consecutive days. Nine of the 19 patients also received oral etidronate 5 mg/kg/day for three months after administration of intravenous therapy. Etidronate administered orally sustained the decreases in urinary hydroxyproline produced by the infusions, whereas levels returned to pretreatment values in most patients receiving only the intravenously administered drug. Serum alkaline phosphatase levels were not reduced in the 10 patients receiving only intravenously administered etidronate, but they declined by approximately 50 percent in the nine patients who received the additional orally administered etidronate. Transiliac-crest bone biopsy specimens obtained three months after intravenous therapy revealed a regular lamellar structure, compared with the characteristic woven pattern of pagetic bone. In all four patients with hypercalcemia of malignancy, normocalcemia was achieved by the 10th day of treatment using a dosage of 4.3 mg/kg/day. Oral etidronate therapy was beneficial in maintaining normocalcemia. PMID- 3103439 TI - Defective release of tissue plasminogen activator in systemic and cutaneous vasculitis. AB - The fibrinolytic system in a group of 23 patients with vasculitis and 10 patients with the cutaneous vasculitis atrophie blanche were studied. These patients were found to have markedly suppressed release of vascular tissue plasminogen activator (t-PA) stores whether the disease was active or in remission. The control group had releasable t-PA levels of 0.70 +/- 0.10 IU/ml of plasma. Levels of releasable t-PA in the patient population were 0.09 +/- 0.03 IU/ml for those with active vasculitis (p less than 0.0001 compared with the control group by the Student t test), 0.23 +/- 0.12 IU/ml for those with inactive vasculitis (p less than 0.001), and 0.03 +/- 0.01 IU/ml for those with atrophie blanche (p less than 0.0001). It is concluded that there is a generalized defect in plasminogen activator in a variety of vasculitides. Such a defect may contribute to the pathogenesis of lesions as well as the thromboembolic disease that may be observed in these patients. PMID- 3103440 TI - Hepatic complications of total parenteral nutrition. AB - Total parenteral nutrition is now widely used in the treatment of nutritional depletion. Among problems that persist in the use of this technique, the development of hepatic abnormalities has received increasing attention. In this review, the current understanding of the pathogenesis and management of liver injury during short-term total parenteral nutrition is summarized. These complications include fatty liver, cholestasis, and nonspecific triaditis. The experience with hepatic complications during long-term total parenteral nutrition is also reviewed. Evidence that progressive liver injury develops in some patients requiring lifelong total parenteral nutrition raises a serious dilemma for both patients and physicians. Better understanding of the pathogenesis is required before appropriate treatment can be prescribed. PMID- 3103441 TI - Pulmonary tuberculosis in elderly men. AB - The clinical manifestations, predisposing factors, and diagnostic approach to 29 young men and 35 elderly men with pulmonary tuberculosis admitted to a Veterans Administration hospital were compared. Elderly men had a higher number of underlying conditions such as atherosclerosis, previous gastrectomy, and malignancy, whereas alcoholism was more prevalent in the younger group. The classic symptoms and signs of tuberculosis were noted in a significantly higher proportion of the younger group: fever (62 percent versus 31 percent), weight loss (76 percent versus 34 percent), night sweats (48 percent versus 6 percent), sputum production (76 percent versus 48 percent), and hemoptysis (40 percent versus 17 percent) (p less than 0.05). Abnormal mentation was more common in the elderly group (31 percent versus 10 percent) (p less than 0.05). Radiographic findings were similar in both groups. Mortality related to tuberculosis was 20 percent in elderly men versus 3 percent in the younger men (p less than 0.05). Tuberculosis is frequently not considered in the differential diagnosis when elderly patients present with multiple medical problems and nonspecific complaints. Since there are differences in the clinical presentation and the outcome of pulmonary tuberculosis in elderly patients, a high index of suspicion for the disease should be maintained. PMID- 3103442 TI - Difluoromethylornithine, an effective new treatment of Gambian trypanosomiasis. Results in five patients. AB - Recent studies have shown DL-alpha-difluoromethylornithine (eflornithine), an inhibitor of polyamine biosynthesis, to be curative in various Trypanosoma species infections of laboratory animals. Five patients are described with Gambian trypanosomiasis treated in Belgium with difluoromethylornithine, using various intravenous and oral dosage schedules. Three patients had late-stage and two had early-stage disease. Difluoromethylornithine treatment was associated with clearing of parasites from blood within one to four days, a trend towards normalization of all altered biologic values associated with the disease, and marked amelioration of clinical symptoms. Side effects of difluoromethylornithine, including loose stools in three patients and both anemia, and a decrease in auditory acuity in one patient, were mild, transient, and never required interruption of drug treatment. The presence of difluoromethylornithine in cerebrospinal fluid, determined in three patients, demonstrated that difluoromethylornithine penetrates into the central nervous system. In three patients, follow-up of at least 24 months after treatment demonstrated a continued healthy state without evidence of relapse. These promising, albeit preliminary, results of difluoromethylornithine therapy, even in patients with central nervous system involvement, indicate that extended clinical trials are warranted to determine the optimal dosage regimen in patients with early- and late-stage disease. PMID- 3103443 TI - Acute cryoglobulinemic renal failure after intravenous infusion of gamma globulin. AB - A 39-year-old woman had mixed IgM/IgG cryoglobulinemia, but was later found to have a lymphoma that produced an IgM kappa paraprotein with rheumatoid factor activity. With intermittent chlorambucil and prednisone therapy, the lymphoma was controlled for five years and she had no evidence of cryoglobulinemia. Because of the presence of intractable pulmonary infection and hypogammaglobulinemia G, she was given an intravenous infusion of gamma globulin. Within 72 hours, renal failure and a sustained decrease in serum concentrations of IgM and IgG began concurrently. A kidney biopsy specimen obtained five days after the infusion showed hyaline "thrombi" in numerous glomerular capillaries and glomerular necrosis, consistent with acute, severe mixed cryoglobulinemic nephropathy. Immunostaining showed strong positivity for IgM, IgG, and light chains in glomerular capillary lumina and subendothelial sites; immunostaining with a monoclonal antiidiotypic antibody specific for the patient's paraprotein established the presence of the rheumatoid factor paraprotein in the deposits. These observations strongly suggest that complexes consisting of IgM kappa rheumatoid factor, IgG, and complement initiated the renal damage. Therefore, demonstrable serum rheumatoid factor activity in patients with B cell neoplasms should be considered a contraindication to the administration of intravenous gamma globulin. PMID- 3103444 TI - Myopericarditis as an initial presentation of meningococcemia. Unusual manifestation of infection with serotype W135. AB - Acute meningococcemia is a dramatic clinical syndrome from infection with the gram-negative diplococcus, Neisseria meningitidis. Although pericarditis may complicate the course of meningococcemia, it is distinctly unusual as a presenting sign. A case of disseminated meningococcemia presenting as acute myopericarditis is reported. The serotype isolated, type W135, was a sporadic cause of N. meningitidis in the Boston area. Although the patient had meningitis, bacteremia, and myopericarditis, his course was uncomplicated with early institution of antibiotic therapy. PMID- 3103445 TI - Calcium-stimulated synthesis of vasodilator renal microvascular prostanoids. PMID- 3103446 TI - Platelet calmodulin concentration in essential hypertension and in Bartter's syndrome. PMID- 3103447 TI - Lessons from a nursing home. PMID- 3103448 TI - The new pulmonary math. Applying the a/A ratio. PMID- 3103449 TI - How diagnoses are changing in long-term care. PMID- 3103450 TI - Prospective pricing system by diagnosis-related groups: comparison of federal diagnosis-related groups with high-risk obstetric care groups. AB - Of 468 diagnosis-related groups identified by the federal government for Medicaid reimbursement, 15 are related to obstetric hospital care. Each diagnosis-related group is considered a distinct group in which cases are homogeneous with respect to resource consumption. Because the diagnosis-related group system is based primarily on data from community and secondary care hospitals, it does not differentiate sufficiently among high-risk obstetric patients seen at tertiary care institutions, such as Florida's Regional Perinatal Intensive Care Centers. We developed an alternative scheme for diagnosis-related groups, called obstetric care groups, using the federal diagnosis-related groups as the model from which to depart. Data collected for 4192 women during a 2 1/2-year period indicate that obstetric care groups provide more homogeneous groups than diagnosis-related groups for our population of high-risk patients. The obstetric care groups differentiate between no complications, one complication, and two or more complications, while the diagnosis-related groups differentiate only between no complications and one or more complications. Also, complications for obstetric care groups are based on only 19 diagnoses that contribute significantly to resource consumption, while the list of possible complications exceeds 200 for diagnosis-related groups. Although the obstetric care group classification system is simpler than that for diagnosis-related groups, it results in a more accurate reimbursement of hospitalization charges for high-risk obstetric care. PMID- 3103451 TI - Preterm labor: stimulation of arachidonic acid metabolism in human amnion cells by bacterial products. AB - There is a strong association between preterm labor and infection. Some potentially pathogenic bacteria have phospholipase activity, and it has been suggested that release of phospholipase from these organisms may increase prostaglandin E2 synthesis in amnion cells and hence initiate preterm labor. In this study we established monolayer amnion cell cultures from tissue collected at elective cesarean section at term before labor. Cells were prelabeled with tritiated arachidonic acid and then further incubated after addition of 2%, 5%, or 10% (vol/vol) filtered medium in which either group B beta-hemolytic streptococcus, Streptococcus viridans, Escherichia coli, Bacteroides fragilis, or Lactobacillus had been growing. Tritiated arachidonic acid and its metabolites released by the amnion cells in these or control incubates were extracted from culture medium and separated by high-performance liquid chromatography. Addition of conditioned medium from each of the organisms with the exception of Lactobacillus caused an increase in overall arachidonic acid metabolism. There was an increase in the ratio of cyclooxygenase to lipoxgenase metabolism and in prostaglandin E2 production in particular when compared to controls. The profile of arachidonic acid metabolism in amnion cells following addition of filtered bacterial medium resembled that obtained from amnion cells cultured following spontaneous labor. We suggest that abnormal bacterial colonization of the genital tract may lead to an increase in arachidonic acid metabolism in amnion cells with an increase in prostaglandin E2 production and the consequent initiation of preterm labor. PMID- 3103452 TI - Synaptophysin expression in neuroendocrine neoplasms as determined by immunocytochemistry. AB - Synaptophysin is an integral membrane glycoprotein originally isolated from presynaptic vesicles of bovine neurons. The authors have studied a wide spectrum of neuroendocrine (NE) neoplasms by immunofluorescence microscopy on cryostat sections of freshly frozen tissues using a monoclonal antibody to this protein (SY 38). Without exception, they found the identical--or a very similar--protein expressed in all neuroblastomas, ganglioneuroblastomas, ganglioneuromas, pheochromocytomas, and paragangliomas studied. In these "neural" type NE neoplasms, synaptophysin was coexpressed with neurofilament proteins. Synaptophysin was also demonstrated in NE neoplasms of "epithelial" type in which it was predominantly coexpressed with cytokeratins and desmoplakin. It was invariably found in all variants of islet cell neoplasms and in all medullary thyroid carcinomas. Synaptophysin was also demonstrated in several adenomas of the hypophysis and parathyroids, in the majority of carcinoids of the bronchopulmonary and gastrointestinal tracts, and in many, though not all, NE carcinomas of the same sites, and of the skin. Conversely, SY 38 did not immunostain any of a large number of benign and malignant non-NE epithelial neoplasms; nor was any immunostaining obtained in a group of mesenchymal tumors. It is remarkable that SY 38 did not immunostain a number of malignant melanomas, including several that were immunostained for neuron-specific enolase (NSE) and several neuropeptides. Parallel studies conducted on conventionally fixed, paraffin-embedded tissue sections immunostained by the use of the avidin-biotin complex technique yielded very similar results. The findings indicate that synaptophysin is expressed in the whole range of NE neoplasms without detectable relation to the expression of other NE markers such as NSE, serotonin, and neuropeptides. Nor could the expression of synaptophysin by these tumors be correlated with their epithelial and/or neural cytoskeletal characteristics, their clinical aggressiveness, or the presence or absence of endocrinologic abnormalities. While the consistent expression of synaptophysin by the "neural" type of NE neoplasms would seem predictable its presence in diverse benign and malignant NE tumors of "epithelial" type is remarkable. It is concluded that synaptophysin is a significant as well as novel NE marker, and the use of antibody SY 38 as a broad range marker for the study and diagnosis of NE neoplasms is proposed. PMID- 3103453 TI - A rapidly dividing human medulloblastoma cell line (D283 MED) expresses all three neurofilament subunits. AB - The majority of cells in a rapidly dividing human medulloblastoma cell line (D283 MED) are shown to express the two high-molecular-weight human neurofilament (NF) subunits, whereas a minority express the low-molecular-weight NF subunit. These three polypeptides are integral subunits of the intermediate filaments (IFs) found in normal neurons. Other cell type-specific IF proteins (keratin, desmin, and glial filament polypeptides) are not present in D283 MED cells. Further, the immunocytochemical, immunochemical and ultrastructural data suggest that the neurofilaments in these cells are abnormal, possibly because of a paucity of the low-molecular-weight NF subunit. This is the first human cell line derived from a central nervous system tumor that is capable of expressing all three NF triplet proteins. It is a unique model system for studies of normal and abnormal human NF metabolism as well as for probing the cell biology of medulloblastomas. PMID- 3103454 TI - IL-2 receptor expression in human lymphoid lesions. Immunohistochemical study of 166 cases. AB - Interleukin-2 (IL-2) receptor expression is a feature of T-cell activation and T cell neoplasia. Expression of the IL-2 receptor in human lymphoid lesions was studied in a series of 166 immunophenotyped cases, including nodal and extranodal reactive lymphoid proliferations (44 cases), low-grade B-cell lymphomas (27 cases), intermediate and high grade B cell lymphomas (42 cases), peripheral T cell lymphomas (13 cases), Hodgkin's disease (12 cases), histiocytic proliferations (15 cases), nonhematopoietic tumors (16 cases), and miscellaneous lesions (7 cases). Low levels of receptor expression were seen in reactive lymphoid lesions, low-grade B-cell lymphomas, and nonhematopoietic tumors (20%, 7%, and 25% of cases, respectively, with greater than 10% positive cells). High levels of receptor expression were seen in cases of peripheral T-cell lymphoma and histiocytic proliferations (86% and 100% of cases, respectively, with greater than 10% positive cells). Intermediate levels of expression were seen in Hodgkin's disease (including Reed-Sternberg cells) and some cases of intermediate and high-grade B-cell lymphomas (58% and 50% of cases, respectively, with greater than 10% positive cells). IL-2 receptor expression is not confined to T-cell neoplasia, but is also a feature of neoplastic and nonneoplastic histiocytic proliferations, Hodgkin's disease, and some intermediate and high-grade B-cell lymphomas. Biologic and therapeutic implications are discussed. PMID- 3103455 TI - Immunoreactivity for Leu-7 in neurofibrosarcoma and other spindle cell sarcomas of soft tissue. AB - Monoclonal antibodies to Leu-7 have been reported to recognize a constituent of myelin-associated glycoprotein. Because of this, the authors studied 20 cases of neurofibrosarcoma (NFS), 7 of leiomyosarcoma (LMS), 3 of fibrosarcoma (FS), 8 of malignant fibrous histiocytoma (MFH), 5 of monophasic spindle cell synovial sarcoma (MSS), 5 of neurilemmoma, and 5 of neurofibroma for Leu-7 reactivity, to determine its utility in differential diagnosis. Selected examples of each tumor type were also studied ultrastructurally. Leu-7 was compared with the expression of S-100 protein, myelin basic protein, desmin, cytokeratin, and epithelial membrane antigen in the 43 neoplasms. Fifteen examples of NFS, 2 of LMS, and 2 of MSS were Leu-7+; 2 neurofibromas and 4 neurilemmomas also demonstrated reactivity with this antibody. In contrast, all cases of FS and MFH were Leu-7-. Synovial sarcomas could be effectively separated from NFS by reactivities for cytokeratin and epithelial membrane antigen in the former, but not the latter, lesions. However, LMSs and NFSs demonstrated significant immunocytochemical overlap, including shared positivity for S-100, desmin, and myelin basic protein in several cases. These results suggest that Leu-7 has restricted utility in immunohistochemical diagnosis, and must be utilized only in concert with other antigens. Moreover, it would appear that in selected instances, smooth-muscle and neurogenic sarcomas must be separated on the basis of clinical, histopathologic, and ultrastructural features alone. PMID- 3103456 TI - Conflicts of interest associated with the psychiatric hospitalization of children. AB - Several possible conflicts of interest are reviewed involving the psychiatric hospitalization of children and adolescents. The roles of physicians, for-profit psychiatric hospitals, and medical universities are examined and possible remedies offered. PMID- 3103457 TI - Stride length and its determinants in humans, early hominids, primates, and mammals. AB - Primate stride lengths during quadrupedal locomotion are very long when compared to those of nonprimate quadrupedal mammals at the speed of trot/gallop transition. These exceptional lengths are a consequence of the relatively long limbs of primates and the large angular excursions of their limbs during quadrupedalism. When quadrupedal primates employ bipedal gaits they exhibit much lower angular excursions. Consequently their bipedal stride lengths do not appear to be exceptional in length when compared to other mammals. Angular excursions of the lower limbs of modern humans are not exceptionally large. However, when running, humans exhibit relatively long periods of flight (i.e., they have low duty factors) when compared to other mammals including primates. Because of these long periods of flight and their relative long lower limbs, humans have running stride lengths that are at the lower end of the range of stride lengths of quadrupedal primates. The stride length of the Laetoli hominid trails are evaluated in this context. PMID- 3103458 TI - Acuity of selective mechanisms operating on ABO, Rh, and MN blood groups. AB - Selection in ABO, Rh, and MN blood groups was studied in 216 matings and their children in an endogamous population. Incompatibility status with respect to these three systems was considered simultaneously. There is no effect of incompatibility on number of pregnancies. Analysis of variance between groups confirms that prenatal loss is associated with incompatibility, and it is greater when the matings are incompatible for any two systems. There is no significant intergenerational change in ABO and Rh polymorphisms. Segregation analysis for the ABO system suggests that there is no significant difference in the proportion of A, B, and O children, based on the compatibility of the parents, while analysis for Rh-D system showed a segregation distortion which is not related to the known antigenic specificities (mother-child incompatibility). PMID- 3103459 TI - Femoral diaphyseal histomorphometric age determinations for the Shanidar 3, 4, 5, and 6 Neandertals and Neandertal longevity. AB - Histomorphometric analysis of femoral diaphyseal fragments from the Shanidar 3, 4, 5, and 6 Neandertals provide age at death estimates of 41 (+/- 6.7), 36 (+/- 6.7), 40 (+/- 6.7), and 24 (+/- 6.7) years. These determinations are in agreement with previous macroscopic age assessments. Since the Shanidar 3, 4, and 5 (and slightly younger Shanidar 1) individuals are among the oldest known Neandertals, these age determinations suggest that significant postreproductive survival was rare among the Neandertals and a phenomenon primarily of anatomically modern humans. PMID- 3103460 TI - Pliocene hominid partial mandible from Tabarin, Baringo, Kenya. AB - Sediments in the Tugen Hills, west of Lake Baringo, Kenya, form one of the best fossiliferous successions known in Africa spanning the period from 14 my to less than 4 my. Hominoid fossils have previously been recovered from a number of localities in the region. We describe here a new hominid mandible (KNM-TH 13150) from the site of Tabarin, in the Chemeron Formation. Isotopic determinations on a tuff below the fossiliferous horizon gives dates of 4.96 my and 5.25 my. The associated fauna is consistent with these results and independently suggests a minimum age for the specimen of 4.15 my. Although fragmentary, the preserved morphology of the Tabarin mandible is consistent with the diagnosis of the Pliocene hominid Australopithecus afarensis. It can be distinguished from all other currently recognized hominoid taxa. PMID- 3103461 TI - ABO blood groups in a natural population of black-handed tamarins (Saguinus midas niger). AB - Eighty-one black-handed tamarins from the Tucurui region were tested for human type ABO blood groups by salivary inhibition tests. Eleven belonged to the A group, 45 to B, and 25 to AB. The serum samples were tested for the presence of agglutinins having specificities like those of humans. The ABO system appeared to be polymorphic, with three alleles occurring at the following frequencies: A = 0.26, B = 0.66, and O = 0.08. The observed distribution fitted the expected on the basis of Hardy-Weinberg equilibrium. PMID- 3103462 TI - Calcium, cell shrinkage, and prolytic state of human red blood cells. AB - The effects of intracellular calcium, or Cac, on the Na permeability of human red blood cells were examined during 3-h incubations with the Ca ionophore A23187 and varied external Ca, Cao. Above 3 microM Cao, Nac increased significantly as ATP decreased. Maintenance of normal ATP with vanadate did not prevent the gain of Nac. Similar amounts of Nac were gained in 3 h by ouabain-treated cells exposed to the K ionophore valinomycin or by cells osmotically shrunken. Cells shrunken with sucrose also exhibited partial loss of Kc. When the cells with increased Nac were subsequently transferred to Na-free, high-K medium, the Nac and Kc that had changed slowly over 3 h returned toward normal within 10 min. The development of irreversible high cation permeability in shrunken cells was not prevented by a variety of transport inhibitors. These observations and cell volume distributions suggest that prolonged shrinkage induces a subpopulation of cells to become highly cation permeable, or "prolytic". The major effect of Cac on Na permeability appears to be an indirect consequence of cell shrinkage due to KCl loss. PMID- 3103463 TI - Cytosolic free calcium concentration and glucose transport in isolated cardiac myocytes. AB - The role of cytosolic free Ca2+ concentration, [Cai], in mediating insulin's stimulatory effect on glucose transport was investigated in isolated Ca2+ tolerant rat ventricular cells. Approximately 98% of glucose transport in isolated myocytes was inhibited by phloretin. Insulin-accelerated glucose transport by 50-115% over basal transport rate. Removal of extracellular Ca2+ had no effect on either the basal transport rate or insulin's stimulatory action, indicating that extracellular Ca2+ was not necessary for insulin's effect to be manifest. Addition of A23187 had no effect on glucose transport rate. Under basal conditions, [Cai] was 167 +/- 12 nM as measured by fura-2 fluorescence and 239 +/ 22 nM by null-point titration with arsenazo III. Loading cells with fura-2 did not affect basal glucose transport rates. In addition, the stimulatory effect of insulin on glucose transport was preserved in fura-2 loaded cells. In paired experiments, insulin did not increase [Cai] as measured by fura-2 fluorescence or null-point titration despite acceleration of glucose transport. In contrast, addition of KCl (40 mM) increased [Cai] from 168 +/- 30 to 287 +/- 51 nM and resulted in 50% reduction in glucose transport rate. In other experiments designed to control for the hyperosmolar effects of KCl, NaCl (40 mM) caused no change in [Cai] but also inhibited glucose transport rate by 50%. We conclude that an elevation in [Cai] is unlikely to be the intracellular signal mediating insulin's effect on glucose transport since insulin's stimulatory effect was not reduced by Ca2+ -free media, insulin had no detectable effect on [Cai], and elevation of [Cai] by KCl did not result in stimulation of glucose transport. PMID- 3103464 TI - Effects of TPA on short-circuit current across frog skin. AB - TPA (12-O-tetradecanoylphorbol-13-acetate) is an effective tumor promoter that affects a variety of ion transport processes. To examine the relationship between effects on transport and growth and differentiation, we have been studying the actions of TPA on frog skin, a particularly well-characterized epithelium. We have reported that high concentrations of TPA stimulate base-line short-circuit current (ISC) and inhibit the subsequent natriferic action of vasopressin. The current study of 89 preparations extends those findings. The Km of the stimulatory effect of TPA is approximately 3 nM; this high affinity indicates that the transport phenomenon does not simply reflect a nonspecific interaction of phorbol ester with the plasma membranes. TPA acts largely or entirely at the mucosal surface of both split and whole skins; thus the sidedness of the effect does not arise from adsorption onto the underlying connective tissue when TPA is applied to the serosal surface of whole skin. Amiloride, an inhibitor of apical Na+ entry, abolishes ISC across frog skins pretreated with TPA. The phorbol ester also increases ISC across split skins, preparations which do not produce net Cl transport. Indomethacin (1 microM) blocks PGE1 release, but does not alter the response to TPA at a fivefold lower concentration than previously used. NDGA (nordihydroguaretic acid, 10 microM), an inhibitor of the lipoxygenase pathway, partially inhibited the responses of ISC to 8 nM TPA. The present results indicate that frog skin is highly responsive to TPA at concentrations known to activate protein kinase C in broken-cell preparations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103465 TI - Precursors of ribose 5-phosphate suppress expression of glucose-regulated proteins in LLC-PK1 cells. AB - Withdrawal of glucose from the medium bathing mammalian cells in culture results in cessation of growth and induces the synthesis of two stress proteins (Mr approximately 94-100 kDa and 78-80 kDa) that have been termed glucose-regulated proteins (GRPs). In LLC-PK1 cells, proteins of the same molecular weights, assayed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography, are fully induced by 24 h in glucose-free medium. The GRPs from LLC-PK1 cells cross-react with antibodies to GRPs of nonpolar cells, confirming their identification. Since glucose is not essential for energy production in cultured cells, but is essential for ribose 5-phosphate and nucleotide biosynthesis (Wice et al. J. Biol. Chem. 256: 7812-7819, 1981), we tested the effect of several precursors of ribose 5-phosphate on the induction of GRPs. The addition of 25 mM fructose or galactose to glucose-free medium suppressed the induction of GRPs. The pyrimidine ribonucleosides uridine and cytidine also suppressed GRP synthesis, ribose and the purine ribonucleosides guanosine and adenosine suppressed partially. The results, coupled with indirect evidence in the literature, lead to the suggestion that cell ribose 5-phosphate or a related metabolite regulates the expression of GRPs. PMID- 3103466 TI - Contraction of rat thoracic aorta strips induced by phorbol 12-myristate 13 acetate. AB - Phorbol 12-myristate 13-acetate (PMA) induced a slow and progressive increase in tension of rat thoracic aorta strips in the presence of extracellular Ca2+. Complete relaxation could not be obtained in Ca2+-free buffer containing 1 mM ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) and 10(-7) M PMA. In the absence of extracellular Ca2+, PMA (10(-7) M) induced a small but sustained contraction which was not altered by the addition of another 2 mM EGTA and 3 X 10(-5) M verapamil. Papaverine (10(-4) M) relaxed the PMA-induced contraction to the base line, but phentolamine (10(-5) M), cyproheptadine (10(-5) M), atropine (10(-5) M) and tetrodotoxine (10(-6) M) did not change the contraction. Ca2+-depleted muscle strips, prepared by four repeated applications of 10(-7) M norepinephrine in Ca2+-free buffer, were contracted by 10(-7) M PMA, but at a lower maximum tension than nontreated strips. The action of PMA on rat aorta strips in Ca2+-free buffer did not require the presence of the adventitial layer or endothelial cells. These results suggest that PMA may induce activation of protein kinase C and smooth muscle contraction in the absence of extracellular Ca2+, without an increase in myoplasmic Ca2+. PMID- 3103467 TI - Glucocorticoid-mediated activation of muscle branched-chain alpha-keto acid dehydrogenase in vivo. AB - Muscle branched-chain alpha-keto acid dehydrogenase, the rate-limiting enzyme for branched-chain amino acid oxidation in skeletal muscle, was measured after treatment of rats with glucocorticoids. Cortisone treatment (10 mg X 100 g body wt-1 X day-1 for 2-5 days) resulted in an approximate doubling of the percentage of active enzyme. To further characterize this effect, the enzyme complex was measured 4 h after the intraperitoneal injection of 6 alpha-methylprednisolone, a water-soluble glucocorticoid with rapid onset effects. The percentage of active enzyme increased linearly as the dose of methylprednisolone was increased from 0.125 to 12.5 mg/100 g body wt, while total enzyme activity was unchanged. Administration of insulin with glucose had no significant effect on the activity of the enzyme. However, treatment of rats with insulin and glucose after methylprednisolone administration partially blocked branched-chain alpha-keto acid dehydrogenase activation. The activity of the enzyme complex was correlated with the concentration of leucine in plasma and muscle. Activation of skeletal muscle branched-chain alpha-keto acid dehydrogenase by increased glucocorticoids may play a role in the acceleration of branched-chain amino acid oxidation observed during severe stress. PMID- 3103468 TI - Total CO2 absorption in the distal tubule of the rat. AB - By use of in vivo microperfusion methodology, we assessed proton secretion (acidification) in the superficial distal tubule of the rat by determining the rate of total CO2 (tCO2) absorption (JtCO2). In these studies, we compared the JtCO2 in rats fed a diet that increased urine pH to the JtCO2 in rats fed a high protein diet that reduced urine pH. The effect of amiloride added to the perfusate, used in rats fed the high-protein diet, was also examined. In rats, Group 1, fed a commercial diet, urine pH was 6.9; plasma tCO2 was 30.0 mM, and JtCO2 was 15.5 +/- 5.3 pmol X mm-1 X min-1. Following the ingestion of a high protein diet the night before study, the urine pH fell to 5.6 and the plasma tCO2 to 28.2 mM. The JtCO2 in this group, Group 2, 41.1 +/- 4.8 was significantly greater than Group 1, P less than 0.05. The late distal transepithelial potential difference was comparable in both groups, -50.3 +/- 4.3 vs. -45.2 +/- 3.1 mV, P not significant. In a third group, Group 3, amiloride (10(-4) M) was added to the perfusate of rats prepared as in Group 2. JtCO2 was 23.4 +/- 0.4 pmol X mm-1 X min-1, significantly less than Group 2, P less than 0.05. The transepithelial potential difference was reduced to -4.0 +/- 2.3 mV, P less than 0.01 vs. Group 2. We conclude that the superficial distal tubule of the rat responds to subtle stimuli to increase proton secretion and contributes to urinary acidification. The rate of acidification can be influenced by alterations in the electrical profile across the acidifying epithelium. PMID- 3103469 TI - HCO3 accumulation in proximal tubule: roles of carbonic anhydrase, luminal buffers, and pH. AB - Most of filtered bicarbonate is reabsorbed in the early proximal tubule, and the high blood-to-lumen HCO3 concentration gradient generated is then maintained in the distal proximal tubule. To determine the factor(s) that prevent reaccumulation of HCO3 in the lumen, surface proximal tubules of the rat kidney were perfused in vivo. All perfusion solutions were similar in ionic composition to late proximal tubule fluid but, instead of HCO3, contained sulfate (SO4) or N 2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES). Bicarbonate concentration ([HCO3]L) was measured by microcalorimetry, while collected fluid PCO2 was maintained in vitro at either renal cortical or atmospheric levels. A new single microelectrode was used to simultaneously measure PCO2 and luminal pH (pHL). With SO4 solution, pHL was 6.84 +/- 0.06, PCO2 was 50.8 +/- 5.0 mmHg, and [HCO3]L was 8.7 +/- 0.9 mM. When 10(-3) M acetazolamide (ATZ) was added to the perfusate, pHL was 7.00 +/- 0.08, PCO2 remained unchanged, [HCO3]L was 12.1 +/- 1.3 mM, and the rate of HCO3 accumulation increased by approximately 50%. When SO4 was replaced with HEPES, pHL increased to 7.18 +/- 0.05, PCO2 was unchanged, [HCO3]L was 16.5 +/- 1.4 mM, and the rate of HCO3 accumulation doubled. Because measured [HCO3]L and that calculated from pHL and PCO2 were approximately the same, the net gain of HCO3 occurred in vivo, a result of either HCO3 backflux and/or intraluminal generation from CO2. By allowing the collected fluid PCO2 to fall to near zero prior to [HCO3]L measurement, we estimate that approximately 50% of the total gain of HCO3 with all solutions was due to backflux.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103470 TI - Effect of potassium depletion and protein intake in vivo on renal tubular bicarbonate transport in vitro. AB - These studies evaluated the effect of decreased dietary potassium and increased dietary protein content in rabbits on systemic acid-base parameters, urine pH, and segmental renal tubular bicarbonate handling in vitro. Animals fed a potassium-deficient high-protein diet (KD) for 2 wk developed metabolic acidosis (arterial blood pH 7.31 vs. 7.43) and excreted a more acid urine than control animals fed a diet with normal amounts of potassium and protein; whereas, animals fed the same potassium deficient diet to which supplemental potassium was added (KD + K+) excreted an even more acid urine and had a blood pH of 7.36. In superficial proximal convoluted and straight tubules, there were no differences in rates of fluid and total CO2 absorption between control and KD tubules. Cortical collecting tubules obtained from KD and KD + K+ animals absorbed, and control tubules secreted total CO2 in vitro. With an ambient potassium concentration of 2.5 mM, collecting tubules obtained from the inner stripe of the outer medulla of KD animals absorbed significantly less total CO2 than control tubules. The same tendency was observed in collecting tubules from the outer stripe of the outer medulla. Plasma aldosterone levels fell with development of potassium depletion. Administration of deoxycorticosterone for 1 day to KD animals was associated with a lower urine pH and higher arterial blood pH than in untreated KD animals and with increased total CO2 absorption by both cortical collecting tubules and tubules from the inner stripe of the outer medulla.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103471 TI - Cerebral circulation, metabolism, and blood-brain barrier of rats in hypocapnic hypoxia. AB - The effects of hypoxic hypoxia on physiological variables, cerebral circulation, cerebral metabolism, and blood-brain barrier were investigated in conscious, spontaneously breathing rats by exposing them to an atmosphere containing 7% O2. Hypoxia affected a marked hypotension, hypocapnia, and alkalosis. Cortical tissue high-energy phosphates and glucose content were not affected by hypoxia, glucose 6-phosphate, lactate, and pyruvate levels were significantly increased. Blood brain barrier permeability, regional brain glucose content and lumped constant were not changed by hypoxia. Local cerebral glucose utilization (LCGU) rose by 40 70% of control values in gray matter and by 80-90% in white matter. Under hypoxia, columns of increased and decreased LCGU were detectable in cortical gray matter. Local cerebral blood flow (LCBF) increased by 50-90% in gray matter and by up to 180% in white matter. Coupling between LCGU and LCBF in hypoxia remained unchanged. The data suggest a stimulation of glycolysis, increased glucose transport into the cell, and increased hexokinase activity. The physiological response of gray and white matter to hypoxia obviously differs. Uncoupling of the relation between LCGU and LCBF does not occur. PMID- 3103472 TI - Endothelium-dependent contraction to stretch in canine basilar arteries. AB - Stretch applied to isolated canine basilar arteries caused the development of active tension in rings with endothelium but not in those in which the endothelium had been removed. Blockade of calcium entry with diltiazem or inhibition of cyclooxygenase with indomethacin abolished the endothelium dependent response to stretch. These observations suggest that the endothelium may contribute to the autoregulation of cerebral blood flow during increases in transmural pressure by the increased production and/or release of prostaglandins, which causes activation of the underlying vascular smooth muscle. PMID- 3103473 TI - Glucose turnover in 48-hour-fasted running rats. AB - In fed rats, hyperglycemia develops during exercise. This contrasts with the view based on studies of fasted human and dog that euglycemia is maintained in exercise and glucose production (Ra) controlled by feedback mechanisms. Forty eight-hour-fasted rats (F) were compared to fed rats (C) and overnight food restricted (FR) rats. [3-3H]- and [U-14C] glucose were infused and blood and tissue sampled. During running (21 m/min, 0% grade) Ra increased most in C and least in F and only in F did Ra not significantly exceed glucose disappearance. Plasma glucose increased more in C (3.3 mmol/l) than in FR (1.6 mmol/l) and only modestly (0.6 mmol/l) and transiently in F. Resting liver glycogen and exercise glycogenolysis were highest in C and similar in FR and F. Resting muscle glycogen and exercise glycogenolysis were highest in C and lowest in F. During running, lactate production and gluconeogenesis were higher in FR than in F. At least in rats, responses of production and plasma concentration of glucose to exercise depend on size of liver and muscle glycogen stores; glucose production matches increase in clearance better in fasted than in fed states. Probably glucose production is stimulated by "feedforward" mechanisms and "feedback" mechanisms are added if plasma glucose decreases. PMID- 3103474 TI - Predictors of interepisode symptoms and relapse in affective disorder patients treated with lithium carbonate. AB - For 98 affective disorder patients receiving lithium prophylaxis for a mean of 45 months, number of interepisode symptoms correlated with relapse rate. Response to prophylaxis appeared highly determined by prelithium frequency of episodes and duration of lithium treatment. PMID- 3103475 TI - Serotypic antigens of Plasmodium falciparum recognized by serotype-restricted inhibitory human sera. AB - Immune sera from some Cambodian refugees contain functional serotypic antibodies that inhibit invasion of erythrocytes by the Camp strain but not by the FCR-3 strain of Plasmodium falciparum. Using a new assay, the "competitive heterologous antigen assay" (CHAA), the serotypic antibodies in a pool of three inhibitory sera were characterized by the antigens they precipitated. In the CHAA, immunoprecipitation of antigens by antibodies to common or cross-reacting antigenic determinants was blocked with excess heterologous unlabeled FCR-3 antigens before 3H-labeled Camp schizont and merozoite antigens were immunoprecipitated. The predominant Camp strain serotypic antigens revealed after electrophoresis and autoradiography were the major 195 Kd glycoprotein surface antigen (gp195) and its processed products at 150, 83, 73, and possibly 45 Kd. Additional serotypic antigens were identified at 180, 130, 65, 50, and 32 Kd. It is likely that one or more of these serotypic antigens is a target for the serotypic antibodies that inhibit invasion. PMID- 3103476 TI - Modulation of Schistosoma japonicum pulmonary egg granulomas with monoclonal antibodies. AB - We have examined the ability of various Schistosoma japonicum egg antigens to sensitize mice for subsequent secondary pulmonary egg granuloma formation. Further, we produced monoclonal antibodies (Mabs) specific for egg antigens and evaluated their abilities to modulate pulmonary granuloma formation and inhibit soluble egg antigen (SEA)-stimulated lymphocyte blastogenesis. A homogeneous, 140 Kd egg glycoprotein, SJe; 140-GP was nearly as effective as intact eggs in sensitizing for egg-focused pulmonary granuloma formation, while SEA, or the heterogeneous immunoaffinity (IA)-purified C10 antigens were ineffective. The in vivo administration of chronic infection serum (CIS) or Mabs reactive with SJe; 140-GP, to egg-sensitized/egg-challenged mice, modulated pulmonary granuloma formation. Two of these modulatory SJe; 140-GP-specific Mabs (1 A1-1 or 14B3-8), an IgG1, and an IgG3, respectively, did not alter the responses of SEA-stimulated lymph node cells from mice with acute or chronic schistosomiasis japonica. In contrast, another SJe; 140-GP-specific IgG3 Mab (7A6-5), CIS, immunoaffinity purified anti-SEA from CIS, or the non-SEA-binding fraction of CIS, all resulted in dose-related inhibition of SEA-induced proliferation. These data confirm the antibody-driven nature of some immunoregulatory networks in murine schistosomiasis japonica, and extend these observations to include certain Mabs. The immunogenic nature of SJe; 140-GP, and the modulatory and inhibitory activities of Mabs specific for this glycoprotein, indicate it may play a central role in granuloma formation and modulation in this infection. PMID- 3103477 TI - A case report of infantile striatal necrosis with an acute onset. AB - We report here an autopsy case, an 8-year-old boy diagnosed as having infantile striatal necrosis, characterized by a preceding febrile illness followed by acute encephalopathy with abrupt obtundation, seizures and dystonia, with remarkable improvement of the disturbed consciousness and intelligence after TRH-T therapy. These clinical symptoms were linked with bilateral necrosis of the striata on CT scanning. The presented case belonged to a newly described subgroup of the heredogenous disorders that produce necrosis of the putamina in children. PMID- 3103478 TI - Congenital muscular dystrophy with cerebral and ocular malformations (cerebro oculo-muscular syndrome). AB - Two children with the features of the "Muscle, Eye and Brain (MEB) Disease" (SANTAVUORI 1977), i.e. congenital muscular dystrophy (CMD), cerebral malformations and ocular abnormalities are reported and correlations with other inherited autosomal recessive syndromes of CMD, Fukuyama type of CMD and the Walker-Warburg syndrome discussed. The association of CMD and cerebral lesions indicate an unfavourable clinical prognosis. PMID- 3103479 TI - Isoflurane for anaesthesia in the dental chair. a comparison of the incidence of cardiac dysrhythmias during anaesthesia with halothane and isoflurane. AB - A randomised single-blind trial was performed to compare the effects on cardiac rhythm of isoflurane and halothane in 100 dental outpatients having extractions under general anaesthesia in the dental chair without tracheal intubation. The incidence of supraventricular dysrhythmias did not differ significantly. No patient in the isoflurane group developed a ventricular dysrhythmia, whilst nine of those who received halothane did so (p = 0.0013). The quality of anaesthesia was acceptable in the isoflurane group, but induction time was longer (p less than 0.05) and the maximum heart rate was faster (p less than 0.01). There was no difference in the maximum end tidal carbon dioxide concentrations measured in a further 20 cases. PMID- 3103480 TI - Arterial to end tidal CO2 tension differences. PMID- 3103481 TI - Peptide fractionation by high-performance liquid chromatography on an Asahipak GS 320 column: application to determination of the disulfide pairings in ribonuclease F1. AB - High-performance liquid chromatography on an Asahipak GS-320 column using isocratic elution with 0.1 M acetic acid has proven effective for fractionation of peptides of molecular weights lower than 3000. This technique enabled the separation of the peptides derived from digestion of native ribonuclease F1 by trypsin and chymotrypsin in combination with conventional gel filtration through Sephadex G-25 and reversed-phase HPLC. Amino acid analysis of the cystine containing peptides thus obtained revealed the disulfide linkages Cys-6-Cys-102 and Cys-24-Cys-84 in this protein. The behavior of a number of peptides in the HPLC on an Asahipak GS-320 column is described and the separation mechanism is discussed. PMID- 3103482 TI - Isolation and the fluorometric, high-performance liquid chromatographic determination of tacrine. AB - Tacrine (THA; 1,2,3,4-tetrahydro-9-aminoacridine) is an anticholinesterase agent which has been used clinically, most recently in the treatment of Alzheimer-type dementias. This paper describes the methodology for the isolation and quantitation of THA at therapeutic levels in serum from human subjects. Using C18 Bond Elut columns and an HPLC/fluorometry system, this assay exhibits a considerable improvement in sensitivity over previous uv methods, and allows routine testing of THA levels in serum samples of reasonable volume from human subjects. PMID- 3103483 TI - The topography of regio caudalis hypothalami in goose (Anser anser F. domestica). AB - We studied the topography of the caudal hypothalamic region of the goose on brain sections stained with luxol fast blue and cresyl violet in combination according to Kluver-Barrera (1953), or with cresyl violet (Nissl method). In the regio caudalis hypothalami of this bird we identified in agreement with Nomina anatomica avium (Breazile 1979): nucleus premamillaris (PM), nucleus mamillaris lateralis (ML), nucleus mamillaris medialis (MM), nucleus supramamillaris interstitialis (SMI) and nucleus intercalatus (Ic). PMID- 3103484 TI - Low set ears (Lse), a new mutation of the house mouse. AB - A new dominant mutation, low set ears (Lse), in the mouse may be indicative of a mammalian branchial arch syndrome. This developmental anomaly of the external ear is accompanied by eye defects, retarded growth and shortened lifespan. The ear defect can be identified in 13-day embryos. Further studies will determine the effects of the Lse gene on other systems. PMID- 3103485 TI - The ultrastructure of early implantation in the marmoset monkey (Callithrix jacchus). AB - The ultrastructural morphology of the initial stages of implantation in the marmoset monkey (Callithrix jacchus) was studied in pregnant monkeys at known time intervals after ovulation. The earliest samples, obtained 13 days after ovulation, displayed both cytotrophoblast and syncytiotrophoblast. The cytotrophoblast was restricted to the blastocoel, whilst syncytiotrophoblast intruded to the endometrial basal lamina. At later stages, days 16 and 19 after ovulation, both cytotrophoblast and syncytiotrophoblast had extended laterally around the uterus, and the syncytiotrophoblast also extended deeper into the maternal tissues. The mesoderm layer was first discernible at 19 days after ovulation. At 23 days after ovulation the syncytiotrophoblast surrounded the maternal blood vessels entirely. In this study syncytiotrophoblast was not observed to breach the maternal blood vessels, even at 31 days after ovulation. Early cytotrophoblast columns could be seen at 31 days after ovulation. The endothelial cells lining the maternal blood vessels displayed hypertrophy from the earliest stages (day 13) onwards, although a true decidual response was only observed in samples of 23 and 31 days after ovulation. PMID- 3103486 TI - Generalized grand mal seizure after recovery from uncomplicated fentanyl etomidate anesthesia. PMID- 3103487 TI - The influence of hypocarbia on the resolution of transient increases in brain extracellular potassium. AB - The effect of acute hypocarbia on baseline extracellular K+ concentration [( K+]e) and its effect on the ability of the cerebral microenvironment to recover from transient increases in [K+]e has been assessed in rats. Spreading depression of cortical activity was used to present a reproducible K+ load to the extracellular space. Baseline [K+]e and the half-time for resolution of the [K+]e changes seen with spreading depression waves were measured for the hypocarbic and normocarbic states by means of double-barrelled K+ microelectrodes placed approximately 400 micron below the cortical surface. Three spreading depression waves were initiated in each animal for the two CO2 states. In group 1 (n = 10), the rats were initially normocarbic (PaCO2 41.6 +/- 3.0 mmHg; mean +/- SD), then hypocarbic (PaCO2 19.0 +/- 2.5 mmHg) for the second series of measurements. The baseline [K+]e was significantly higher in the normocarbic state 3.4 +/- 0.4 versus 3.0 +/- 0.4 mM l-1, P less than 0.01 (paired t test). During normocarbia, the K+ load (delta[K+]e) presented to the extracellular space following spreading depression was 49.4 +/- 7.5 mM l-1, n = 10 (peak [K+]e - baseline [K+]e). The half-time for resolution of the presented [K+]e load was 24.3 +/- 6.1 s. Following hypocarbia of 1.4 +/- 0.6 h, there was no change in delta[K+]e (49.0 +/ 6.0 mM l-1) but resolution t1/2 had increased to 35.8 +/- 11.2 s, P less than 0.01 paired t test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103488 TI - Respiratory changes induced by parenteral nutrition in postoperative patients undergoing inspiratory pressure support ventilation. PMID- 3103489 TI - [Choice of drugs for neurovegetative stabilization during electroanesthesia in hypertensive patients]. PMID- 3103490 TI - The clinical scope of disopyramide. A clinical symposium. San Antonio, Texas, November 5, 1984. Proceedings. PMID- 3103491 TI - A review of the effects of disopyramide phosphate on left ventricular function and the peripheral circulation. AB - In the absence of preexistent myocardial dysfunction, the risk of producing cardiac decompensation in patients being treated with any of the conventional antiarrhythmic agents is low. The availability of disopyramide for clinical use in 1977 produced optimism for an effective antiarrhythmic agent that was free of the well-known immediate and late toxicities of quinidine and procainamide. Unfortunately, shortly after its clinical introduction, reports appeared that raised concern about the negative inotropic actions of disopyramide and the possible role of this drug in precipitating heart failure. In clinical use, the frequency of adverse effects on ventricular function appeared to be out of proportion to disopyramide's greater negative inotropic activity and the contrasting (augmenting) effect on the peripheral vascular resistance compared to that of either quinidine or procainamide, suggesting that the other factors contributed to these observations. Review of the reported literature reveals that certain factors encourage such adverse reactions. These primarily include the routine use of oral and especially intravenous loading dosages of disopyramide in an effort to attain rapid onset of action, the failure to adequately reduce dosages of disopyramide in the setting of compromised renal function, and, most importantly, the use of standard (and even loading) dosages in patients with active heart failure, compromised left ventricular function, or a history of heart failure. The avoidance of loading dosages of disopyramide, adequate reductions of maintenance dosages in the setting of renal insufficiency, gradual dose titration for additional drug action, and omission of patients with decompensated heart failure or significant left ventricular dysfunction should significantly enhance safety in the use of disopyramide. PMID- 3103492 TI - Pharmacologic evaluation of standard and controlled-release disopyramide. AB - Controlled-release disopyramide offers many potential advantages over the standard formulation for improved patient compliance, possible reduction of concentration-related adverse effects, and predictability of pharmacologic effect. The pharmacology of disopyramide, potential advantages and disadvantages of the use of sustained- (or controlled-)release formulations of drugs, and the preliminary finding of our use of controlled-release disopyramide are described. Controlled-release disopyramide is a promising addition to the antiarrhythmic formulary that may increase the clinical utility of disopyramide. PMID- 3103493 TI - Transfer from immediate-release disopyramide to controlled-release disopyramide. AB - Simulation of serum disopyramide concentrations during transfer from steady-state immediate-release (IR) disopyramide to a sustained-release disopyramide preparation was performed based on pharmacokinetic parameters obtained from IR disopyramide and serum concentrations measured following an initial dose of controlled-release (CR) disopyramide phosphate. Based on the results of simulation, a typical patient with good cardiac, renal, and hepatic function can be transferred from a q 6 h IR disopyramide to an equivalent daily dose of controlled-release disopyramide administered q 12 h beginning at 6 hours after the final IR disopyramide dose. PMID- 3103494 TI - Long-term use of controlled-release disopyramide in patients with severe ventricular arrhythmias. AB - Controlled-release (CR) disopyramide phosphate has been available for the past four years for the management of patients with ventricular arrhythmias. The advantages of this preparation over the earlier form have for most patients been striking. Improved patient compliance as regards dosing, ease in stabilizing blood levels of disopyramide, and effective antiarrhythmic control has been a significant factor in physician satisfaction with this preparation. Studies have demonstrated that effective blood levels are obtained with the 12-hour dosing schedule for controlled-release disopyramide phosphate in both normal volunteers and in patients with cardiac arrhythmias. Concern over the safety of disopyramide in patients with significant underlying heart disease, and especially in patients with a history of congestive heart failure, has been reported in a number of publications. No clinical observations are available in which patients with intractable ventricular arrhythmias have been managed with controlled-release disopyramide phosphate in addition to other appropriate therapy for their cardiac condition. Fifteen patients with significant left ventricular dysfunction were followed for an average of 20.6 months while receiving controlled-release disopyramide phosphate, and control of ventricular arrhythmias was achieved without worsening of left ventricular function. PMID- 3103495 TI - Tentative chromosomal localization of the bovine major histocompatibility complex by in situ hybridization. AB - A genetic region, most likely the major histocompatibility complex, was assigned to bands q13-23 of cattle chromosome 23 by in situ hybridization using a cloned DNA sequence of a class I gene of the pig major histocompatibility complex. PMID- 3103496 TI - Desensitization to factor VIII in a patient with classic hemophilia and C2 deficiency. AB - Factor VIII therapy has been reported to cause anaphylactic reactions in patients with hemophilia. Desensitization attempts have been complicated by severe allergic reactions that have prevented the achievement of protective factor VIII levels. We report successful administration of factor VIII by a graded dose desensitization protocol in a 36-year-old man with hemophilia A who had previously experienced anaphylactic reactions to factor VIII infusions. The reactions were manifested by urticaria, choking, and bronchospasm and were not prevented by pretreatment with antihistamines and corticosteroids. Intradermal skin test with factor VIII was positive. Serum levels of circulating immune complexes were slightly elevated. Persistently low serum C2 levels were consistent with genetic C2 deficiency. These findings suggest the possibility of Type I (IgE mediated) and Type III (immune complex) immunopathogenic mechanisms. Our experience suggests that administration of factor VIII by graded dose desensitization protocol may offer a practical therapeutic approach for management of hemorrhage in patients with classic hemophilia who are allergic to factor VIII. PMID- 3103497 TI - [Determination of factor X Ag by laser immunonephelemetry]. AB - A method of dosage of X Ag factor by laser immunonephelemetry is proposed. This technique, carried out with a rabbit antiserum in the presence of PEG and EDTA, presents the advantage to be sensitive, reproducible and mostly faster than the other immunological methods, such as Electroimmunodiffusion (EID) and Enzyme Linked Immuno-Sorbent Assay (ELISA). It constitutes a simple tool, applicable in the demonstration of an enzyme dysfunction or liver pathology. Finally, it could bring a supplement of information in monitoring antivitamin K therapy. PMID- 3103498 TI - [Compensatory mechanisms and consequences of metabolic acidosis]. PMID- 3103499 TI - [Nosocomial Candida albicans septicemia in parenteral alimentation through a peripheral vein]. AB - Fungal septicaemias during total parenteral nutrition are frequent, but their occurrence during parenteral nutrition via a peripheral vein is uncommon. A case of disseminated candidemia with ocular and renal localizations during parenteral nutrition via a peripheral vein is reported in a 24 year old patient hospitalized for primary cerebellar haemorrhage. The case history showed the importance of early ophthalmologic examination in all septicaemic cases. The diagnosis was confirmed by nine positive blood cultures and immunological tests, but the dosage of soluble antigens remained negative. The part played by a contaminated perfusion bottle out-of-date was suggested, but could not be proved absolutely. The assessment of the immune state could wrongly suggest an acquired immunodeficiency syndrome, for it has been demonstrated that Candida albicans itself had an immunosuppressive activity. PMID- 3103500 TI - Nonequilibrium facilitated transport of carbon dioxide in bicarbonate and bovine albumin solutions. AB - The nonlinear diffusion-reaction equations describing the nonequilibrium transport of CO2 through flat layers of complex but homogeneous aqueous media were solved by an approximate analytical method called the "Combined Damkohler Number" (CDN) technique. Unlike other approximate analytical solutions, the CDN technique is valid for the full range of Damkohler numbers, i.e., for any layer thickness. The present theoretical treatment uses as a basis the equilibrium approach of Stroeve, Hoofd, and Kreuzer which accounts for any species in the solution except for possible carbamate formation (binding of CO2 by the protein). The nonequilibrium model developed here for CO2 transport is the most general technique currently available in the literature. Theoretical results were compared to experimental data from the literature for diffusion in bicarbonate and albumin solutions and were generally in good agreement. Results obtained from numerical calculations were also compared and were found to be in excellent agreement with the CDN results. PMID- 3103501 TI - Analysis of the gas exchange system dynamics during high-frequency ventilation. AB - High-frequency ventilation (HFV) as a form of artificial respiration has attracted interest in recent years as a means of reducing the risk of barotrauma in clinical applications. This paper explores the high-frequency dynamics of the gas exchange system in order to obtain mathematical models that allow optimization studies aimed at answering the question: What is the optimum ventilatory waveform that secures a certain level of gas exchange while minimizing the resulting fluctuations in pleural or alveolar pressure? Two classes of input are considered: sinusoids and band-limited white noise. A model for the dynamic relation between tracheal flow and CO2 tension is obtained from experimental data which, in combination with existing models relating tracheal flow to pleural or alveolar pressure, allows optimization of the input flow waveform for a given level of CO2 elimination rate. The developed relation between CO2 elimination rate and input was verified by experimentally measured arterial CO2 tension. PMID- 3103502 TI - Effects of zeranol on reproduction in beef bulls: luteinizing hormone, follicle stimulating hormone, and testosterone secretion in response to gonadotropin releasing hormone and human chorionic gonadotropin. AB - Effects of zeranol on the maturation of the adenohypophyseal-gonadal axis were studied in beef bulls. Calves were implanted with 36 mg of zeranol at 3-month intervals from birth through 6 months of age (group 2, n = 10) or were not treated (control group 1, n = 10). After 9 months, group-2 calves were given implants of 36 mg of zeranol at 3-month intervals through 18 months of age (group 2B, n = 5) or were not reimplanted (group 2A, n = 5). Areas under the curves outlined by concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone for 6 hours after the administration of 100 micrograms of gonadotropin-releasing hormone (GnRH) were calculated. Gonadotropin releasing hormone was administered at 3-month intervals from 1.5 through 19.5 months of age. Areas under the curves for concentrations of testosterone for 4 hours after the administration of 10,000 IU of human chorionic gonadotropin (HCG) at 4.5, 7.5, and 10.5 months or 1,000 IU at 13.5 and 16.5 months of age also were calculated. The amount of FSH released was greater (P less than 0.05) for group-2 than for group-1 calves at 4.5 and 7.5 months of age. The amount of FSH released in groups 2A and 2B tended (P less than 0.10) to be greater than that for group 1. Significant differences between groups 2A and 2B were not observed. The amount of LH released at 7.5 months of age was less for groups 1 and 2 than that at earlier ages, and the decrease was greater (P less than 0.05) for group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103503 TI - Topographic localization of gastric lesions and key role of plasma bicarbonate concentration in dogs with experimentally induced gastric dilatation. AB - The canine gastric response to acute dilatation, its correlation with selected systemic cardiovascular changes, and preliminary study of its modulation by membrane-stabilizing agents were studied in 21 Beagle dogs. Gastric mucosal damage and adverse cardiovascular sequelae were induced by inflation of an intragastric balloon to 60 mm of Hg in each anesthetized dog for 2.5 hours. At this time, dogs were given 1 of 4 treatments: control; lidocaine HCl, 2.2 mg bolus + 66 micrograms/min, IV; prednisolone succinate, 6.6 mg, IV; and zinc sulfate, 2.2 mg bolus + 66 micrograms/min, IV. After treatments were given, there was a 4-hour deflation period. Throughout the 6.5 hours, continuous measurements were made of stroke volume, arterial blood pressure, PaO2, PaCO2, and plasma HCO3 concentration. Gastric lesions, assessed by planimetric analysis of ulcer indices, were limited to the fundus and corpus and were significantly decreased by lidocaine administration. As seen by histopathologic examination, a sharply delineated transverse area bordering the corporeal-antral junction near the lesser curvature demonstrated minimal resistance to ulceration and showed mucus depletion. Plasma HCO3- concentration, base excess, and CO2 values were negatively correlated with development of gastric damage, indicating that plasma HCO3- concentration has a key role in mucosal resistance to ulcerogenesis. PMID- 3103504 TI - Dexamethasone inhibits the antigen-induced contractile activity and release of inflammatory mediators in isolated guinea pig lung tissue. AB - Treatment for 24 h in vitro with dexamethasone inhibited the antigen-induced contractile response in guinea pig tracheal rings and parenchymal strips without inhibiting the contractile response of the tissues to either methacholine or histamine, respectively. Antigen-induced histamine release was inhibited by approximately 50% in both tissues by prior treatment with dexamethasone. Dexamethasone treatment also inhibited the release of immunoreactive sulfidopeptide leukotriene from parenchymal strips. In tracheal rings, dexamethasone treatment reduced spontaneous release of all cyclooxygenase metabolites (PGE2, PGF2 alpha, TXB2, PGD2, and 6-k-PGF1 alpha were tested), with the exception of PGD2, and also inhibited the antigen-induced release of all cyclooxygenase metabolites studied. Dexamethasone-treatment did not inhibit the spontaneous release of cyclooxygenase metabolites in the guinea pig lung strips, and only modestly inhibited the antigen-induced release of PGE2, PGF2 alpha, and PGD2. The results suggest that the inhibition of contractile response of guinea pig lung strips and airway tissue to antigen by dexamethasone is the result of a reduced release of inflammatory mediators. The inhibition by dexamethasone of antigen-induced release of mast cell mediators from guinea pig lung parenchyma contrasts with results previously obtained with human parenchymal lung tissue. PMID- 3103505 TI - Current concepts of the pathogenesis of sarcoidosis. PMID- 3103506 TI - Chemotherapy by regional perfusion for limb melanoma. AB - The administration of chemotherapy by isolated regional perfusion was developed in 1957 at Tulane University and was found to be of greatest benefit for patient with melanoma of the limbs. From 1957 to 1984, 897 patients were treated by this method. The 10-year survival rate for 831 patients with primary melanoma was 77 per cent. Women survived longer than men, with 10-year rates of 81 per cent and 65 per cent, respectively. Prophylactic lymph node dissection was of benefit for males with poor prognosis distal lower limb lesions, but other groups did not benefit. Primary lesions on the arm and thigh did better than lesions of the hand or foot, with plantar and subungual lesions having the least favorable results. Thickness, level, and histologic type were also significant prognostic indicators. Thirty-three patients with locally recurrent melanoma (stage II) treated by perfusion and excision had a 10-year survival rate of 59 per cent. For 129 patients with metastases to the regional lymph nodes (IIIB), perfusion plus RLND produced a 10-year rate of 51 per cent; survival rates for those with a single positive node was 64 per cent. Seventy patients with satellitosis or intransit metastases (IIIA) had a 10-year survival rate of 23 per cent. Thirty eight patients with metastases to limbs from unknown primaries had a 10-year survival rate of 52 per cent. The overall 10-year rate for all stage III patients was 41 per cent. Perfusion produced useful palliation in 144 patients with limb melanoma in the presence of systemic metastases. PMID- 3103507 TI - [Acute hepatitis in childhood. Study of 96 cases and 1-year follow-up]. AB - Authors studied 96 children, 56 boys and 40 girls, aged 1 to 16 years, with acute viral hepatitis. 53 patients were diagnosed of hepatitis a virus (HAV) detecting antibodies to HAV of the IgM class; 11 patients were diagnosed of hepatitis B virus (HBV) detecting serologic markers; 32 patients were diagnosed of non A-non B hepatitis. There were no serologic evidence of infection with cytomegalovirus and Epstein-barr virus. They report an analytical and clinical comparative study of acute viral hepatitis, and their evolution during a year, not finding any significative statistic difference. Two patients with HBV remained chronically infected. PMID- 3103508 TI - [Combination of hydantoins and valproate. Evidence of its teratogenic effect in 4 consecutive gestations]. AB - Four siblings are presented with a malformative syndrome. All were born to an epileptic woman treated with phenytoin and valproic acid. A considerable high fetal pathology is found. Perhaps increased teratogenic effects are related with this pharmacological association not previously described. PMID- 3103509 TI - [Neonatal pathologic fracture and neurofibromatosis]. PMID- 3103510 TI - The frequency of lupus anticoagulant in systemic lupus erythematosus. A study of sixty consecutive patients by activated partial thromboplastin time, Russell viper venom time, and anticardiolipin antibody level. AB - Recent reviews have suggested a higher frequency of the lupus anticoagulant or related antiphospholipid antibodies in patients with systemic lupus erythematosus (21% to 65%) than was found in earlier studies (6% to 18%). In our study of 60 consecutive patients, we found the frequency of the lupus anticoagulant by Russell viper venom time was 6.7% (95% confidence interval, 16.2 to 1.8) and by anticardiolipin antibody assay was 25% (95% Cl, 37.0 to 15.7), compared with 0% (p = not significant) and 2.5% (p = 0.002), respectively, in the normal control population. The Russell viper venom time (p = 0.0001 by t-test) and anticardiolipin antibody levels (p = 0.01) were significantly associated with presumed thrombotic events (stroke, deep venous thrombosis, and digital gangrene). No association with miscarriage or pulmonary hypertension was detected. The Russell viper venom time was more specific than the anticardiolipin antibody level in the prediction of past presumed thrombotic events, miscarriage, or pulmonary hypertension (100% compared with 84%, p = 0.01). PMID- 3103511 TI - Bicarbonate therapy for organic acidosis: the case for its continued use. AB - Critics of bicarbonate therapy for life-threatening lactic acidosis have argued that the treatment is not only ineffective but that it also worsens morbidity and mortality. We critically examine the six major arguments used to condemn alkali treatment. We highlight the shortcomings of frequently cited uncontrolled human studies, experiments in animals, and in-vitro chemical analyses not clearly related to the human condition. The damaging hemodynamic effects of acidemia, which centralizes blood volume while depressing myocardial contraction (thereby causing hemodynamic collapse), are discussed and offered in support of alkali therapy. We also emphasize the extreme sensitivity of patients with acidosis to further small decreases in serum bicarbonate concentration or increases in arterial PCO2. In short, we have found no basis by which to condemn the use of alkali and believe that those who have scorned its use have yet to demonstrate its danger clearly. Until that time, sodium bicarbonate should remain the standard of therapy for this life-threatening condition. PMID- 3103512 TI - The cholesterol saga: whither health promotion? PMID- 3103513 TI - Bicarbonate therapy in severe diabetic ketoacidosis. PMID- 3103514 TI - Colonization resistance and preoperative preparation of patients for colorectal surgery. PMID- 3103515 TI - Infection prevention during induction of remission in children with newly diagnosed acute leukemia. PMID- 3103516 TI - [Prolactin stimulation test using TRH in affective disorders (72 cases)]. AB - Authors report results of stimulation test of prolactin by T.R.H. in 72 inpatients with affective disorders. They find well known effects of physiological factors (age, sex), and treatments (neuroleptics, lithium, L-Dopa). They did statistical analysis on plasma levels before and after T.R.H. stimulation. This test has no value for differential diagnosis between types of depressions. But it shows particular relation between high levels of prolactin and bipolarity. PMID- 3103517 TI - [Effect of the administration of killed Lactobacillus acidophilus on the survival of suckling mice infected with a strain of enterotoxigenic Escherichia coli]. AB - After oral administration of 10(2) to 10(5) CFU of Escherichia coli B41 (0101:K 99+:ST+) to 24-48 h old suckling mice (Swiss OF1), a 80 to 100% mortality rate is observed within three days. We compared the effect of the oral treatment with a lyophilized preparation of heat-killed Lactobacillus acidophilus and with sterile water on the mortality rate of newborn mice. In six out of seven assays, the heat killed L. acidophilus administration extended survival of infected suckling mice (P ranging from 0.019 to less than 0.001). In another test, result was contradictory. A global analysis indicated that the two treatments were statistically different (P less than 0.001). Lactic acid was unable to induce protection. PMID- 3103518 TI - Biochemical abnormalities in anorexia nervosa and bulimia. AB - We report the biochemical results in 90 women presenting to an eating disorders clinic: 61 who had bulimia, 22 with anorexia nervosa and seven unclassified. The results were compared with 30 control women. The group of women with an eating disorder had significantly higher concentrations of total CO2, calcium, AST, ALT, ALP, albumin and cholesterol and significantly lower concentrations of potassium, chloride and phosphate in the plasma. The elevated calcium could be accounted for in part by an increase in total CO2 and an increase in albumin. Hypokalaemia was strongly associated with self-induced vomiting and laxative abuse. Biochemical abnormalities occurred in both forms of eating disorders; however, hypercholesterolaemia was more common in anorexia nervosa and abnormal liver enzymes were more common in bulimia. PMID- 3103519 TI - [Current status of somatocrinin, or GRF, a hypothalamic growth hormone-secreting factor]. AB - This short review on GRF is divided into two parts: laboratory findings: Current status of the knowledge on the primary structure of all the GRFs isolated from mammalian sources; structure activity relationships as obtained with synthetic fragments and analogs of GRF; the mechanisms of action of GRF in vitro and in vivo; the localization by techniques of hypothalamic GRF neurons. CLINICAL STUDIES: A summary of past and current clinical studies with hGRF or fragments of hGRF establishing the dose range/effect in normal young adults; pharmacokinetics of hGRF; intravenous, sub-cutaneous and intranasal modes of administration; multi hours perfusions; the use of hGRF alone and in combination with other releasing factors as a diagnostic tool; early clinical results of stimulation of statural growth. Limited bibliography. PMID- 3103520 TI - [Treatment with human growth hormones in 1986]. AB - The availability of large supplies of synthetic human growth hormone (hGH) and somatocrinin (GRF) may lead to new therapeutic possibilities, however still hypothetical. This review briefly summarizes the main data previously acquired with extracted hGH in medical practice: clinical pharmacology, long-term results in completely GH-deficient children, short-term results in partial or atypical GH deficiency and in some other types of severe growth retardation. The data reported up to now (July 1986) from clinical trials using synthetic hGHs and GRF are preliminary. However they allow to discuss guidelines for the new trials, unavoidably long and accurately designed, which are needed for extending and delineating the clinical use of new human growth hormones. PMID- 3103521 TI - [Hashimoto's thyroiditis with intra-thyroid production of a monoclonal antithyroglobulin autoantibody]. AB - A 46-year old man had an Hashimoto's thyroiditis. The disease was particular by the voluminous goiter, associated with pressure symptoms and by the presence of a monoclonal Ig.G Kappa. Because of a possibly associated lymphoma of the thyroid, a total thyroidectomy was performed. Post-operative course showed a rapid and total disappearance of monoclonal Ig.G and antithyroglobulin autoantibodies. There was no pathological feature of thyroid malignancy. We could show that the monoclonal Ig.G bore an antithyroglobulin activity and that this monoclonal antithyroglobulin autoantibody was produced with in the thyroid. This case demonstrate that a monoclonal proliferation can arise from autoreactive B lymphocytes infiltrating the thyroid during Hashimoto's thyroiditis. Such a mechanism could explain, in some cases, the well-known association between lymphomas of the thyroid and Hashimoto's thyroiditis. PMID- 3103522 TI - [Treatment of cyclic attacks of acute intermittent porphyria with an LH-RH agonist administered by the intranasal route]. AB - A 31 year old woman suffering of acute intermittent porphyria (AIP) developed within 9 months 7 cyclical attacks occurring in a average of 5,2 days before menses. In order to inhibit ovulation, we experiment a long-acting agonist LH-RH (D-SER (TBU) 6-EA10 LH-RH--Buserelin) administered during 8 months by nasal spray. Menses did not occur during the test and the patient developed only 2 attacks. The initial ovarian stimulation phase lasted 15 days and was marked by the induction of an AIP attack after 3 days of treatment and occurrence of ovarian cysts. Our case suggests that LH-RH analogues may be useful in the prevention of cyclical attacks of porphyria. PMID- 3103523 TI - [Ultrasensitive TSH : a new diagnostic approach to hyperthyroidism]. AB - The value of new ultrasensitive and rapid immunoradiometric assay of thyroid stimulating hormone (TSH) for the diagnosis of hyperthyroidism was assessed in 130 patients with suspected hyperthyroidism and in 330 controls. The diagnosis was established by the clinical evaluation, thyroid scintigraphy and serum concentrations of thyroid hormones. Using the ROC (Receiver Operating Characteristic) curve methodology which allows the optimization of sensitivity and specificity, the physician can choose the "Cut-off" value between hyperthyroidism and euthyroidism. Two points of the curve seem to be interesting : using the "cut-off" value of 0.1 mUI/l, sensitivity is 0.98 and specificity is 0.98 ; using the "cut-off" value of 0.3 mUI/l, sensitivity is 1.00 and specificity is 0.92. Using the association TSH and FT4 (Free Thyroxin), sensitivity is 0.94 and specificity is 0.99. Sixty four per cent of euthyroid patients with TSH under 0.3 mUI/l have one or several hot nodules and only two have no thyroid disease. A TRH (Thyrotrophin Releasing Hormone) test was carried out in 63 patients with suspected thyrotoxicosis : basal and TRH stimulated TSH levels were under 0.1 mUI/l. This immunoradiometric assay for TSH may simplify the approach to thyroid function testing in patients with suspected thyrotoxicosis : a basal TSH under 0.3 mUI/l is sufficient to confirm a clinical suspicion of thyrotoxicosis without TRH test within four hours. In a department devoted to testing thyroid function, this new method provides a great benefit in cost and work. PMID- 3103524 TI - In vitro secretion and uptake of radioactive vitamin A in rats fed different dietary proteins. AB - Generally, protein energy malnutrition is accompanied with vitamin A deficiency. The present study was undertaken to evaluate the importance of the quality and the quantity of dietary proteins on the in vitro secretion and uptake of vitamin A in growing rats. The results show that the in vitro release of radioactive vitamin A was greater in rats fed Bengal gram diets as compared to those fed casein diets. However, this relationship between the two groups of rats was reversed for the in vitro uptake of radioactive vitamin A from plasma by various extrahepatic tissues. Thus the vitamin A status of the animal is profoundly influenced by the quality and the quantity of dietary proteins. PMID- 3103525 TI - Ultrastructure and activity of some enzymes of energy metabolism of skeletal muscle in experimental energy deficiency. AB - The ultrastructure of skeletal muscle and activity of some enzymes of energy metabolism were studied to assess the effect of a deficiency of dietary energy and subsequent nutritional rehabilitation in 24 young, growing, healthy rhesus monkeys. Electron microscopy of muscles on energy-deficient animals showed thinning of myofibrils with widening of interfibrillar space and enlargement and accumulation of mitochondria at subsarcolemmal level. There was an apparent significant reduction in the fiber size. Muscle samples from each animal were analyzed for enzymes representative of glycolysis (phosphofructokinase [PFK] and lactate dehydrogenase [LDH], citric-acid cycle (isocitric dehydrogenase [ICDH] and citrate synthase [CS] and regeneration of ATP (creatine kinase [CK]. PFK and LDH activities were significantly augmented in energy-deficient animals. The increase in LDH activity resulted from a large increase in MU (skeletal muscle) LDH subunit. The activities of CS and ICDH were reduced. No alteration of CK in muscle and serum was observed. The morphological structure and enzyme activities returned to normal after nutritional rehabilitation. PMID- 3103526 TI - Cerebral glucose metabolism in the Lennox-Gastaut syndrome. AB - We used positron emission tomography with fluorine 18-labeled 2-deoxyglucose to study cerebral glucose metabolism in 10 patients with Lennox-Gastaut syndrome who had normal neuroradiological studies. The scans showed decreased metabolic rates relative both to those in the caudate nucleus and to normal control values in 3 patients whose seizures began before the age of 1, as well as in a patient with hyperprolinemia. No patient had a region of persistent focal hypometabolism. Metabolic rates increased in parallel with increased electroencephalographic discharges in 1 patient; 3 patients had lower metabolic rates when the electroencephalogram showed epileptiform discharges and while the patients were taking barbiturates. PMID- 3103527 TI - Lennox-Gastaut syndrome and positron emission tomography. PMID- 3103528 TI - The Lennox-Gastaut syndrome: metabolic subtypes determined by 2-deoxy 2[18F]fluoro-D-glucose positron emission tomography. AB - We employed positron emission tomography (PET) with 2-deoxy-2[18F]fluoro-D glucose (FDG) to study local cerebral glucose utilization in 15 children who had Lennox-Gastaut syndrome. Our results show that LGS can be classified into four predominant subtypes, each with a distinct metabolic pattern: unilateral focal hypometabolism, unilateral diffuse hypometabolism, bilateral diffuse hypometabolism, and normal. Functional disturbances seen on FDG-PET did not always correlate with abnormalities revealed by x-ray computed tomographic scan. This classification of Lennox-Gastaut syndrome into four major metabolic subtypes not only provides a new perspective toward understanding cerebral function in this complex syndrome, but may also prove useful in the clinical management of these patients. PMID- 3103529 TI - Averufanin is an aflatoxin B1 precursor between averantin and averufin in the biosynthetic pathway. AB - Wild-type Aspergillus parasiticus produces, in addition to the colorless aflatoxins, a number of pigmented secondary metabolites. Examination of these pigments demonstrated that a major component was an anthraquinone, averufanin. Radiolabeling studies with [14C]averufanin showed that 23% of the label was incorporated into aflatoxin B1 by the wild type and that 31% of the label was incorporated into O-methylsterigmatocystin by a non-aflatoxin-producing isolate. In similar studies with blocked mutants of A. parasiticus the 14C label from averufanin was accumulated in averufin (72%) and versicolorin A (54%) but not averantin. The results demonstrate that averufanin is a biosynthetic precursor of aflatoxin B1 between averantin and averufin. PMID- 3103530 TI - Arginine deiminase system and bacterial adaptation to acid environments. AB - The arginine deiminase system in a variety of streptococci and in Pseudomonas aeruginosa was found to be unusually acid tolerant in that arginolysis occurred at pH values well below the minima for growth and glycolysis. The acid tolerance of the system allowed bacteria to survive potentially lethal acidification through production of ammonia to raise the environmental pH value. PMID- 3103531 TI - Expression of cloned monkey metallothionein in Escherichia coli. AB - Expression vectors were constructed in which a cDNA specifying the monkey kidney metallothionein-II (MT-II) was linked directly to the lambda PR promoter. Enhanced expression of MT-II in Escherichia coli was observed when two initiation signals were tandemly linked to the MT-II gene and the lambda cI+ host cells were induced by nalidixic acid. PMID- 3103532 TI - Specific and sensitive plate assay for bacterial lipases. AB - A plate assay to detect bacterial lipase (EC 3.1.1.3) in a medium containing trioleoylglycerol and the fluorescent dye rhodamine B is presented. Substrate hydrolysis causes the formation of orange fluorescent halos around bacterial colonies visible upon UV irradiation. The logarithm of lipase activity from cell free culture supernatants is linearly correlated with the diameter of halos, thereby allowing quantitation of lipase activities ranging from 1 to 30 nkat. PMID- 3103533 TI - Involvement of the spore coat in germination of Bacillus cereus T spores. AB - Bacillus cereus T spores were prepared on fortified nutrient agar, and the spore coat and outer membrane were extracted by 0.5% sodium dodecyl sulfate-100 mM dithiothreitol in 0.1 M sodium chloride (SDS-DTT) at pH 10.5 (coat-defective spores). Coat-defective spores in L-alanine plus adenosine germinated slowly and to a lesser extent than spores not treated with SDS-DTT, as determined by decrease in absorbance and release of dipicolinic acid and Ca2+. Spores germinated in calcium dipicolinate only after treatment with SDS-DTT. Biphasic and triphasic germination kinetics were observed with normal and coat-defective spores, respectively, in an environment with temperature increasing from 20 to 65 degrees C at a rate of 1 degree C/min. Therefore, the physical and biochemical processes involved in germination are modified by coat removal. The data suggest that a portion of the germination apparatus located interior to the coat may be protected by the coat and outer membrane or that the coat and outer membrane otherwise enhance germination in L-alanine plus adenosine. When coat-defective spores were heat activated with the dialyzed (12,000-Mr cutoff) components extracted from the spores, germination of the SDS-DTT-treated spores was enhanced; thus, one or more components located in the spore coat or outer membrane with a molecular weight greater than 12,000 were essential for fast germination. PMID- 3103534 TI - Ecophysiological adaptations of anaerobic bacteria to low pH: analysis of anaerobic digestion in acidic bog sediments. AB - The dynamics of anaerobic digestion were examined in the low-pH sediments of Crystal Bog in Wisconsin. The sediments (pH 4.9) contained 71% organic matter and the following concentrations of dissolved gases (micromoles per liter): CO2, 1,140; CH4, 490; and H2, 0.01. The rate of methane production was 6.2 mumol/liter of sediment per h, which is slower than eutrophic, neutral sediments. Microbial metabolic processes displayed the following pH optima: hydrolysis reactions, between 4.2 and 5.6; aceticlastic methanogenesis, 5.2; and hydrogen-consuming reactions, 5.6. The turnover rate constants for key intermediary metabolites were (h-1): glucose, 1.10; lactate, 0.277; acetate, 0.118; and ethanol, 0.089. The populations of anaerobes were low, with hydrolytic groups (10(6)/ml) several orders of magnitude higher than methanogens (10(2)/ml). The addition of carbon electron donors to the sediment resulted in the accumulation of hydrogen, whereas the addition of hydrogen resulted in the accumulation of fatty acids and the inhibition of hydrogen-producing acetogenic reactions. Strains of Lactobacillus, Clostridium, and Sarcina ventriculi were isolated from the bog, and their physiological attributes were characterized in relation to hydrolytic process functions in the sediments. The present studies provide evidence that the pH present in the bog sediments alter anaerobic digestion processes so that total biocatalytic activity is lower but the general carbon and electron flow pathways are similar to those of neutral anoxic sediments. PMID- 3103535 TI - Modification of membrane sulfhydryl groups in bacteriostatic action of nitrite. AB - The mechanism by which nitrite inhibits outgrowing spores of Bacillus cereus T was examined by using techniques developed earlier for nitrite analogs. The morphological stage of inhibition, cooperativity effects, effect of pH on inhibition, kinetics of protection against iodoacetate incorporation into membrane sulfhydryl groups, and protection against the bacteriocidal effect of carboxymethylation by iodoacetate indicate that nitrite acts as a membrane directed sulfhydryl agent. The mechanism by which nitrite modifies the chemical reactivity of the sulfhydryl group could be either direct covalent modification or inactivation through communication with another modified membrane component. Profiles of pH effects suggest that the active agent is the protonated form of nitrite. The nitrite concentrations which modify membrane sulfhydryl activity coincide with those which have a bacteriostatic effect. These results are consistent with membrane sulfhydryl modification as a component of the mechanism of nitrite-induced bacteriostasis in this aerobic sporeformer. PMID- 3103536 TI - Biosynthetic preparation of L-[13C]- and [15N]glutamate by Brevibacterium flavum. AB - The biosynthesis of isotopically labeled L-glutamic acid by the microorganism Brevibacterium flavum was studied with a variety of carbon-13-enriched precursors. The purpose of this study was twofold: to develop techniques for the efficient preparation of labeled L-glutamate with a variety of useful labeling patterns which can be used for other metabolic studies, and to better understand the metabolic events leading to label scrambling in these strains. B. flavum, which is used commercially for the production of monosodium glutamate, has the capability of utilizing glucose or acetate as a sole carbon source, an important criterion from the standpoint of developing labeling strategies. Unfortunately, singly labeled glucose precursors lead to excessive isotopic dilution which reduces their usefulness. Studies with [3-13C]pyruvate indicate that this problem can in principle be overcome by using labeled three-carbon precursors; however, conditions could not be found which would lead to an acceptable yield of isotopically labeled L-glutamate. In contrast, [1-13C]- or [2-13C]acetate provides relatively inexpensive, readily available precursors for the production of selectively labeled, highly enriched L-glutamate. The preparation of L [15N]glutamate from [15N]ammonium sulfate was carried out and is a very effective labeling strategy. Analysis of the isotopic distribution in labeled glutamate provides details about the metabolic pathways in these interesting organisms. PMID- 3103537 TI - [Chemosensitivity testing for 5-FU and 5-FU derivatives using subrenal capsule assay]. AB - An evaluation was made, using in vivo subrenal capsule (SRC) assay, of the chemosensitivity of 12 human neoplastic tissues including 7 gastric cancers, 2 colo-rectal cancers, 2 lung cancers and 1 breast cancer, exposed to 5 fluorouracil (5-FU) and the 5-FU derivatives: tegafur (FT), UFT and hexylcarbamoyl-5-FU (HCFU). The relative variation of tumor size (delta TS/TS0) was calculated as follows: delta TS/TS0 = (TS6-TS0)/TS0 X 100 (%), where TS6 was the tumor size on day 6 and TS0 that on day 0, and more than a 10% decrease of delta TS/TS0 in the treated group was considered as positive for chemosensitivity. Delta TS/TS0 was decreased to -10.9 +/- 11.3% (mean +/- standard deviation) for 5-FU, -13.0 +/- 16.4% for FT, -19.8 +/- 18.2% for UFT and -18.8 +/- 15.1% for HCFU, and the inhibition of tumor growth following exposure to 5-FU correlated well with that following exposure to 5-FU derivatives (5-FU vs. FT, r = 0.659; 5-FU vs. UFT, r = 0.864; 5-FU vs. HCFU, r = 0.729). However, the sensitivity of each tumor varied; for example, the chemosensitivity was positive for 5-FU derivatives, but negative for 5-FU, in some tissues. The SRC assay appears to be useful for selecting sensitive drugs from 5-FU and 5-FU derivatives for individual cancer patients. PMID- 3103538 TI - [A model for the sensitivity determination of anticancer agents against human cancer using nude mice]. AB - Human tumors transplanted into nude BALB/c-nu mice have been used to test the sensitivity of the tumors to various anticancer agents. Three cancer cell lines from the stomach and one from the colon were transplanted into nude mice to establish a standard assay method for selection of effective drugs on individual tumors using the criteria of the Japanese Association of Sensitivity Determination for Carcinostatic Agents. From the LD values of anticancer drugs in nude mice, the appropriate doses of drugs were 6 mg/kg of MMC X 1(i.p.), 50 mg/kg of 5-FU q4d X 3 (i.p.), 120 mg/kg of CPA (i.p.), 30 mg/kg of ACNU (i.p.) 8 mg/kg of CDDP (i.p.) and 8 mg/kg of ADM (i.v.). At 3 weeks after initial treatment, the inhibition rate (IR) of the tumor was calculated from the formula IR = (1-T/C) X 100%, where T is the mean tumor weight of the treated group and C is the mean weight of the untreated group at that time. The tumors respond well to the anticancer agents when IR is more than 58%. PMID- 3103539 TI - [Potentiation of the cytotoxic effects of anticancer drugs on human genitourinary neoplastic cells by recombinant gamma-interferon]. AB - Experiments were performed to ascertain whether or not the cytotoxic effects of various anticancer drugs on five human genitourinary malignant cell lines would be enhanced by recombinant gamma-type interferon. The cells used were as follows: HeLa cells from a uterine cervix cancer, HT-1376 and EJ cells from bladder cancers, ACHN cells from a renal cancer, and PC-3 cells from a prostatic cancer. The effects of the drugs were studied by colony formation assay. The following drugs were used: two metabolic antagonists. cytosine arabinoside (Ara-C) and 5 fluorouracil (5-FU), three antibiotics: adriamycin (ADM), mitomycin C (MMC) and peplomycin (PEP), two alkylating agents: nimustine hydrochloride (ACNU) and melphalan, one vinca alkaloid: vincristine (VCR) and one other drug: cisplatin (CDDP). Interferon used was a preparation of recombinant gamma-type interferon. PEP showed synergistically enhanced cytotoxic effects on HeLa, EJ, HT-1376, and ACHN cells by concomitant application with gamma-IFN. Synergistic cytotoxicity was also detected against HeLa, EJ and ACHN by combined treatment with ADM and gamma-IFN. A similar enhanced cytotoxicity was demonstrated in HT-1376 and PC-3 by 5-FU treatment with gamma-IFN. MMC showed enhanced cytotoxicity only against ACHN cells in the presence of gamma-IFN. The cytotoxic effects of PEP on cells were increased by lower concentrations of gamma-IFN compared with those of other drugs. DNA, RNA and protein synthesis were examined in HeLa cells following combined exposure to PEP and gamma-IFN. The combined therapy was found to produce a specific decrease in DNA synthesis, while yielding no significant inhibition of intracellular RNA and protein synthesis. PMID- 3103540 TI - [A multi-institutional study on postoperative adjuvant immunochemotherapy of gastric cancer (II)]. AB - A multi-institutional cooperative study of postoperative immunochemotherapy for gastric cancer was studied using PSK and/or OK-432 combined with Tegafur (FT) and/or MMC. A total of 3,630 gastrectomized patients from 412 institutions were entered into the study using 6 randomly assigned protocols. Unbiased background cases were analyzed by 4-year or 5-year survival rates (SVR) for each protocol. The efficacy of combined PSK with FT was noticed in all cases of curative operation macroscopically and in n(-) X ps(+) cases (4-y SVR). The combination of MMC, FT and PSK produced better survival than MMC with FT or PSK administration in all cases of macroscopic curative operation (5-y SVR) and in non-curative operation (4-y SVR). The combination of MMC, FT, PSK and OK-432 was effective for poorly differentiated cancer (4-y SVR). Immunochemotherapy with MMC, FT, PSK and OK-432 was more effective in patients with preoperative positive PPD skin test than in those with negative PPD skin test. These results suggested that adjuvant immunochemotherapy using PSK and/or OK-432 combined with MMC and FT is effective for the improved survival of gastrectomized patients with gastric cancer. PMID- 3103541 TI - [A case of parotid tumor showing remarkable regression following hyperthermo chemo-radiotherapy]. AB - A 72-year-old woman developed adenocarcinoma of the left parotid gland. Because of the excessive size of her tumor and the fact that she suffered from severe liver dysfunction, she was treated by hyperthermo-chemo-radiotherapy (HCR therapy). After ten sessions of radiofrequency hyperthermia with HEH 500 (13.56 MHz radiofrequency wave), 50-Gy irradiation from a linac and administration of 33.0g of tegafur in suppository form, the tumor mass showed remarkable regression decreasing in size by as much as 84% on computed tomography. Histologically the tumor which was resected under local anesthesia, showed almost total necrosis. The multidisciplinary HCR therapy was well tolerated and effective as a therapy for cancer in this case. PMID- 3103542 TI - [Successful treatment of advanced gastric cancer by combined cisplatinum, mitomycin C and 5-FU administration. A case report]. AB - A 55-year-old woman with gastric cancer underwent laparotomy and was found to have an unresectable tumor at the MC region, characterized by S3 (invasion into the pancreas), N3, P0, H0, Borrmann-II and moderately differentiated tubular adenocarcinoma. She was then treated by combined administration of cis dichlorodiammine platinum (CDDP), mitomycin C and 5-fluorouracil (5-FU). A complete response was confirmed by upper gastrointestinal roentgenography and endoscopy. Upon reoperation 4 months after the initial laparotomy, a successful total radical gastrectomy with R2 (partially R3) lymph node dissection was performed. Histological examination of the specimens, including the stomach and lymph nodes, revealed no cancer cells in any region. PMID- 3103543 TI - [Comparative study on the cytotoxic effects, on various human tumor cell lines, of recombinant human TNF and IFN (alpha, beta, gamma)]. PMID- 3103544 TI - [Short ischemia of tumor by noradrenalin injected into tumor-feeding arteries after chemotherapy-improved cytotoxic damage on Walker-256]. PMID- 3103545 TI - [Concentration of 5-FU and tegafur in the ascites fluid in patients with peritonitis carcinomatosa after UFT oral administration]. PMID- 3103546 TI - Influence of intravenous fat emulsion on serum bilirubin in very low birthweight neonates. AB - Thirty nine very low birthweight neonates (with a birth weight of 820 to 1500 g and gestation of 27 to 34 weeks) who required total parenteral nutrition were randomly assigned to one of three regimens of administration of fat emulsion for a period of eight days. Groups 1 and 2 received the emulsion at a constant rate over 24 and 16 hours, respectively, beginning with a daily dosage of 1 g/kg and increasing daily by 1 g/kg to a maximum of 4 g/kg. Group 3 received the emulsion at a constant rate of 4 g/kg a day over 24 hours. Plasma concentrations of free fatty acids and serum concentrations of total bilirubin, apparent unbound bilirubin, and albumin were measured at regular intervals. Effects of the three regimens on serum bilirubin measurements were determined. The regimen of fat infusion and rate of infusion seemed to have no effect on serum concentrations of total and apparent unbound bilirubin, although there was a trend towards greater variability in apparent unbound concentrations with the intermittent regimen. PMID- 3103547 TI - Human milk vitamin content after pasteurisation, storage, or tube feeding. AB - We investigated the effect of the composition of the storage container, Holder pasteurisation, and conditions during tube feeding on the concentration of selected vitamins in human milk. Though the fat soluble vitamins A, D, and E were not affected, the concentration of several water soluble vitamins decreased. The lower vitamin C concentration of milk stored in polypropylene containers compared with milk stored in glass containers (29%) was not significant. Holder pasteurisation significantly lowered the concentrations of vitamins C (36%), folacin (31%), and B6 (15%). Tube feeding significantly lowered the concentrations of vitamins C (44%) and B6 (19%), and exposure to phototherapy seemed to lower the vitamin C concentration (53%) further. Low birthweight infants have increased vitamin requirements. Vitamin losses in expressed human milk before or during feeding may increase the incidence of vitamin deficiencies in these babies. PMID- 3103548 TI - Noonan's syndrome and neurofibromatosis. AB - A child with Noonan syndrome and multiple cafe au lait spots, compatible in size and number with von Recklinghausen's neurofibromatosis, is presented. These features may represent a distinct genetic entity rather than the coincidence of two diseases. PMID- 3103549 TI - Preovulatory serum gonadotropin levels in hMG stimulated menstrual cycles in pregnant and nonpregnant patients. AB - In a group of patients undergoing in vitro fertilization, 10 pregnant and 10 nonpregnant, cycles were analysed in retrospect in relation to gonadotropin and steroid hormones. All patients were similar in terms of age, body surface area and initial stimulation protocol. The increase in follicles stimulating hormone (FSH) was significantly higher in the pregnant group through cycle day 8 as compared with cycle day 3 before stimulation. A significant increase in the nonpregnant group was never detectable; the mean FSH levels rather decreased to the baseline value during stimulation after a slight nonsignificant increase. The levels of luteinizing hormone (LH) decreased significantly in pregnant and nonpregnant patients during stimulation. No significant difference in the FSH/LH ratio between the pregnant and nonpregnant group was encountered. Although the mean serum estrogen in the follicular phase and the serum estrogen and progesteron values in the luteal phase were higher in the pregnant patients, no statistically significant difference between groups could be demonstrated, until luteal day 11. It is believed from this study, that a 15-20% increase in serum FSH levels over baseline during the early and mid follicular phase is required for adequate follicular development and steroidogenesis. The determination of serum gonadotropins in the follicular phase in patients who failed to conceive, might reveal differences, which can account for failures in hMG induced cycles. PMID- 3103550 TI - Prostaglandin metabolism in umbilical vessels of smoking and non-smoking mothers. AB - Arachidonic acid (AA) and its metabolites are responsible for the regulation of the umbilical blood flow. We investigated the prostaglandin (PG) synthesis in umbilical arteries and veins of 16 smoking and 17 non-smoking mothers. AA and PGs were analyzed after extraction of samples by means of thin layer chromatography (TLC). Of all the AA metabolites in umbilical arteries and veins, prostacyclin reached the highest concentration. In non-smoking mothers the conversion rate of AA in arteries and veins was similar. The only exception was PGE2 which showed a significantly lower concentration in umbilical veins of smoking mothers. However, the influence of PGE2 on the blood flow of umbilical arteries and veins seems to be of minor importance compared to other vessels. PMID- 3103551 TI - [Evaluation of serum concentrations of FSH, LH, testosterone and prolactin correlated with the cytomorphologic pathology of infertile human semen]. PMID- 3103552 TI - The hotel alternative program: a new trend for cost-containment. PMID- 3103553 TI - Cervical myelopathy, ossification of the posterior longitudinal ligament, and diffuse idiopathic skeletal hyperostosis: problems in investigation. AB - This report describes a patient presenting with a spastic quadriplegia who was found to have both diffuse idiopathic skeletal hyperostosis (DISH) and ossification of the posterior longitudinal ligament (OPLL) in the cervical spine. There was a dramatic worsening of his symptoms during a myelogram examination of the neck. It is suggested that computed tomographic imaging of the neck is the preferred investigative procedure if OPLL is suspected as a cause of cervical myelopathy. PMID- 3103554 TI - [Prevalence of schistosomiasis mansoni in Zairian and Ugandan children of the Aru region in upper Zaire]. PMID- 3103555 TI - Whole body protein kinetics in severely septic patients. The response to glucose infusion and total parenteral nutrition. AB - Rates of whole body protein synthesis and catabolism in normal volunteers and in a group of severely septic patients were isotopically determined. In addition, the effect in the patients of either glucose infusion or total parenteral nutrition (TPN) on protein dynamics was assessed. The basal rate of net protein catabolism (NPC) was significantly higher in the septic patients than in the volunteers (p less than 0.05). The values obtained in the volunteers and patients were 1.44 +/- 0.18 and 2.20 +/- 0.10 g/kg/day, respectively. This increase in NPC was primarily due to a major increase in whole body catabolism that was partially counteracted by a modest increase in protein synthesis. When the patients were infused with glucose (4 mg/kg/min), NPC decreased significantly (p less than 0.001) to 1.96 +/- 0.08 g/kg/day, and during TPN the value was significantly lower again (p less than 0.04) (0.63 +/- 0.28 g/kg/day). In each instance the conservation of host tissue was due to an increase in protein synthesis: the accelerated rate of whole body protein catabolism continued irrespective of the nutritional status. The following conclusions were reached from these data: severely ill septic patients have an accelerated rate of NPC compared with normal volunteers, and this is primarily due to a large increase in whole body protein catabolism; TPN is an effective means of conserving host tissue in severely septic patients via the promotion of whole body protein synthesis; despite the beneficial effect of TPN in these patients, whole body protein catabolism continues unabated, and as a result, protein losses still occur at approximately one fourth the rate seen in the absence of TPN; and there is no obvious advantage in terms of protein-sparing when protein is provided in amounts exceeding 1.5 g/kg/day. PMID- 3103556 TI - Coagulopathy post peritoneovenous shunt. AB - In 1942, 53% of medically treated patients with cirrhosis were dead 6 months after the onset of ascites. Only 30% survived 1 year. This dismal outlook has improved only slightly with advances in medicine. Yet, some internists reject the peritoneovenous shunt (PVS) for this fatal condition even if they are aware that a diminished blood volume causes the abnormal sodium retention responsible for ascites. Their objections are based on life-threatening complications of PVS, especially post shunt coagulopathy (PSC). Blood shed into the peritoneal cavity becomes incoagulable. Such blood is immediately coagulated by a protocoagulant (soluble collagen) and concurrently lysed by tissue plasminogen activator (TPA) secreted by the peritoneal serosa. Wide zones of lysis surround peritoneal tissue placed on fibrin plates. Large volumes of ascitic fluid infused into circulating blood simulates the fate of blood shed into the peritoneal cavity with lysis playing the major role. Addition of ascitic fluid to normal platelet-rich plasma in vitro initiates clot lysis on thromboelastogram (TEG). Epsilon-aminocaproic acid (EACA) counteracts this lysis. EACA and clotting factors normalize the TEG and arrest PSC. Disposal of ascitic fluid at surgery prevents or ameliorates PSC. Mild PSC was encountered only twice in 150+ consecutive patients (1.3%) with only one case being clinically significant (0.6%). Severe PSC occurred seven times in 98 early shunt patients whose ascitic fluid was not discarded. Severe PSC requires shunt interruption and control of bleeding with clotting factors and EACA. Peritoneal lavage with saline prevents the recurrence of PSC on reopening the shunt. In four patients, EACA and clotting factors were adequate to arrest coagulopathy. Three earlier patients died of PSC before its cause and treatment were understood. Proper management eliminates this life-threatening complication, and PSC cannot be considered a deterrent to PVS. Disseminated intravascular coagulopathy (DIC) is produced in experimental animals only by the injection of thrombin or thromboplastin. PSC is a distinct entity differing from DIC; EACA and not heparin is the antidote for PSC. PMID- 3103557 TI - Methemoglobinemia from intravenous nitroglycerin: a word of caution. AB - The dose of intravenously administered nitroglycerin (IV NTG) used to control ischemic chest pain usually is limited by hypotension from decreased preload. Herein we describe 2 patients who tolerated IV NTG without hemodynamic compromise but in whom severe impairment of blood oxygen content developed from methemoglobinemia noted during coronary bypass surgery. Methemoglobinemia must be suspected if chocolate-brown blood is encountered despite a normal arterial oxygen tension and calculated oxygen saturation. Before a methemoglobin level is available, the extent of hypoxemia can be determined by an oximetric oxygen saturation and therapy begun with intravenous administration of methylene blue. These case reports focus attention on the potential deleterious effects of undetected hypoxemia from methemoglobinemia in patients being stabilized with high-dose IV NTG for urgent cardiac surgery. PMID- 3103558 TI - Long-term administration of (-)deprenyl (selegiline), a compound which facilitates dopaminergic tone in the brain, leaves the sensitivity of dopamine receptors to apomorphine unchanged. AB - The effect of repeated administration of the MAO-B enzyme blocker (-)deprenyl on the apomorphine (APO) sensitivity of dopamine (DA) receptors was investigated in rats, and compared to the effect of other drugs influencing the dopaminergic system. APO was given either in a high dose (0.1-0.6 mg/kg), which induces stereotyped behaviour or in a smaller one (0.02 mg/kg) causing sedation. Repeated administration of all the other drugs investigated (except (-)deprenyl), i.e. haloperidol, d-amphetamine, (1 mg/kg s.c., respectively) and the MAO-A blocker clorgyline (0.25 mg/kg s.c.) altered the efficiency of APO on the stereotypy. Haloperidol, clorgyline (0.5 mg/kg s.c.) and imipramine (10 mg/kg i.p.) attenuated the APO-sedation. The long-lasting administration of (-)deprenyl (0.25 mg/kg s.c., daily for 42 days) however, left the effects of APO unchanged, demonstrating that (-)deprenyl facilitates the dopaminergic tone in the rat brain without altering the sensitivity of DA receptors. PMID- 3103559 TI - Cardiovascular reactivity in adult rats pretreated at a suckling age with intracerebroventricular 6-hydroxydopamine. AB - To investigate functional differences in noradrenergic mechanisms of cardiovascular regulation between the hypothalamus and the brainstem, cardiovascular responses to various stimuli were examined in mature rats pretreated with 6-hydroxydopamine (6-OHDA) given i.c.v. at a suckling age which is known to provoke low norepinephrine concentrations in the hypothalamus but not in the brainstem or in peripheral organs. Under alpha-chloralose anesthesia the resting mean arterial pressure (MAP) was significantly lower in the 6-OHDA treated group than in the control group. Pressor response and associated reflexbradycardia produced by i.v. injection of phenylephrine in the two groups were similar. Likewise, carotid occlusion response and clonidine-induced hypotension and bradycardia did not differ between the two groups. Electrical stimulation of the sciatic nerve elicited increases in MAP and heart rate in both groups. However, pressor responses in the treated rats were significantly less than in the controls. Increases in heart rate during stimulation in the treated group were larger than in the controls. These results indicate that a long lasting depletion of norepinephrine in the rat hypothalamus leads to a deterioration of basal level of blood pressure and somatosympathetic reflexes, yet baroreflexes remain intact. PMID- 3103560 TI - Nifedipine increases oxygen saturation level of myoglobin in the rat heart during hypoxia. AB - Rat hearts were perfused by means of the Langendorff's technique and paced at 150/min. Oxygen saturation level of myocardial myoglobin was measured continuously according to an optical method, by which the intracellular oxygen level in the myocardial cells can be monitored continuously. Krebs-Henseleit solution was bubbled with a gas mixture containing either 95% O2 + 5% CO2 (high oxygen solution) or 95% N2 + 5% CO2 (anoxic solution), or both (low oxygen solution). Hypoxia was produced by changing the perfusion fluid from high to low oxygen solution. After 10 min of hypoxia, drugs were infused into the inflow tube at a rate of 0.1 ml/min for 10 min. Hypoxia increased coronary flow by about 25%, decreased oxygen saturation level of myoglobin by 23.1-35.7%, without a marked change in left ventricular pressure. Nifedipine (1.0 microgram/ml) increased oxygen saturation level, which had been reduced by hypoxia, by 16-27%. Nifedipine at the concentration of 0.1 microgram/ml also increased the oxygen saturation level of myocardial myoglobin slightly, but at the concentration of 10 micrograms/ml it decreased. Nitroglycerin (100 micrograms/kg) increased the oxygen saturation level, which had been decreased by hypoxia, by 6-8%, whereas dipyridamole (100 micrograms/ml) did not. It is concluded that nifedipine as well as nitroglycerin can increase the oxygen saturation level of myocardial myoglobin during hypoxia, suggesting that both drugs may increase the intracellular oxygen tension in the hypoxic heart. PMID- 3103561 TI - Staphylococcus aureus bacteremia. Clinical, serologic, and echocardiographic findings in patients with and without endocarditis. AB - Seventy-two adult patients with Staphylococcus aureus bacteremia were prospectively studied clinically, serologically, and echocardiographically. Multivariate analysis identified four parameters that significantly predicted endocarditis in staphylococcemic patients at time of initial evaluation: absence of a primary site of infection; community acquisition of infection; metastatic sequelae; and valvular vegetations detected by echocardiography. Echocardiography was most predictive of endocarditis in patients with community-acquired S aureus bacteremia from an obvious primary focus. In 11 (69%) of 16 patients with endocarditis and vegetations on two-dimensional echocardiography, this technique also revealed other important findings, including ventricular dilatation, and/or underlying valvular lesions. In 18% of patients with S aureus bacteremia without stigmata of endocarditis, echocardiography provided information that led to a diagnosis of endocarditis and a subsequent change in therapy. Our findings support the routine use of two-dimensional echocardiography in all cases of community-acquired S aureus bacteremia to identify occult endocarditis in patients without classic stigmata of disease, and to provide important prognostic data in clinically apparent endocarditis. PMID- 3103562 TI - Tocainide-induced reversible agranulocytosis and anemia. AB - Tocainide is an effective oral antiarrhythmic agent. We report a 77-year-old man who developed agranulocytosis and anemia while receiving tocainide therapy. These hematologic abnormalities were detected on routine evaluation six weeks after beginning tocainide therapy. The absolute granulocyte count decreased to 50/mm3 (0.05 X 10(9)/L). The anemia was mild; hemoglobin count, 10.9 g/dL (109 g/L). These abnormalities were associated with local and stromal adipocytic bone marrow damage, and decreased production of red blood cells and granulocytes. The platelet count was not affected. The patient had no evidence of infection. Hematologic values were restored to normal two weeks after discontinuation of tocainide therapy, indicating that bone marrow toxicity of tocainide is reversible. PMID- 3103563 TI - Solid-phase radioimmunoassay for IgG antibodies to Staphylococcus epidermidis. Use in serious coagulase-negative staphylococcal infections. AB - A radioimmunoassay (RIA) for human IgG antibodies to Staphylococcus epidermidis was compared with an agar-gel-diffusion assay in patients with a variety of infections. The RIA was sensitive and reproducible and discriminated between endocarditis and uncomplicated bacteremias due to coagulase-negative staphylococci. Anti-S epidermidis antibodies by RIA were elevated in 16 (89%) of 18 patients with coagulase-negative staphylococcal endocarditis but in none of 28 patients with uncomplicated bacteremia (n = 18) or with blood culture contaminated with these organisms (n = 10). Cross-reacting IgG antibodies to S epidermidis antigens were also detected by RIA in 13 (76%) of 17 patients with Staphylococcus aureus endocarditis but in none of 17 patients with nonvalvular S aureus bacteremias and in none of 25 patients with endocarditis or bacteremia caused by other pathogens. Agar-gel-diffusion assay was less sensitive than RIA for detecting coagulase-negative staphylococcal endocarditis, being positive in nine (50%) of 18 such patients. This RIA may be useful in distinguishing patients with endocarditis from those with nonvalvular staphylococcemias or blood culture contamination. PMID- 3103564 TI - Acute-subacute lead poisoning. Clinical findings and comparative study of diagnostic tests. AB - A prospective study of an epidemic outbreak of acute lead poisoning characterized by unusual clinical and analytic manifestations was carried out. Its source was traced to lead-contaminated flour. Thirty-two adult patients presented with classic clinical symptoms of saturnism; however, 13 severely poisoned patients simultaneously manifested unusual clinical features such as hemolytic anemia and multiorgan dysfunction. We compared the diagnostic value of the different toxicity markers in 68 of 136 adults exposed to lead. Porphyrin precursors, urine levels of lead, and results from an edetic acid-provocative test gave poor diagnostic information and low correlation values with lead levels in blood. However, erythrocyte delta-aminolevulinic acid dehydratase activity showed a closer correlation with lead levels in blood, although we observed a frequent overlap of results in severe cases. The test for levels of lead in blood was the most reliable, suitable, and simplest test performed, and gave the best correlation with the external dose of lead, the clinical situation, and the toxicologic effects described by 12 different analytic data. PMID- 3103565 TI - [Anomalies in left ventricular systolic function disclosed by exercise testing in chronic aortic insufficiency. Study by cavitary scintigraphy]. AB - Fifty-two patients with a symptomatic chronic aortic insufficiency underwent radionuclide angiography. The following parameters were measured at rest and at peak exercise: ejection fraction, regurgitant fraction, ventricular volumes, stroke volume, cardiac output and an index of systemic arterial resistance. The ventricular dimensions, the thickness of the septal and posterior walls, left ventricular myocardial mass and endsystolic stress were determined by 2D echocardiography. The patients were divided into 3 groups based on left ventricular changes on exercise: the first group (18 patients) had physiological left ventricular adaptation to exercise (increased ejection fraction, reduced endsystolic volume); a second group of 18 patients had moderate left ventricular dysfunction (absence of increase in ejection fraction and a reduction of less than 20% of endsystolic volume with respect to basal values); a third group of 17 patients had what was considered to be severe left ventricular dysfunction (decreased ejection fraction of over 5% and increased endsystolic volume of over 20% with respect to basal values). There was no significant difference between the three groups with respect to basal values of ejection fraction, ventricular volumes and systemic arterial resistance. On exercise, the heart rate, blood pressure and systemic arterial resistances varied in a comparable manner in each of the three groups. The left ventricular dimensions and myocardial mass were identical in the three groups. Only left ventricular endsystolic strain tended to be higher in the third group of patients compared with the other two, but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103566 TI - [The contribution of magnetic resonance imaging in congenital heart diseases]. AB - The diagnostic value of magnetic resonance imaging (MRI) was assessed in 30 patients with congenital heart disease, including 7 patients with postoperative sequellae. The images obtained by synchronizing the MRI spectrometer with the electrocardiogramme were recorded in 2 or 3 different planes (sagittal, frontal and transverse) and compared to clinical, angiographic and/or echocardiographic data. The MRI provided high resolution tomographic images enabling spatial reconstitution of the heart by the use of different planes. These images were particularly useful for showing the position and dimensions of the ventricles (both chamber size and wall thickness) and their relationship to the atria and great vessels. These results confirm the value of this new non-invasive imaging technique in the diagnosis of congenital heart disease, not counting the additional information on blood flow and tissue characterisation that will soon become available. PMID- 3103567 TI - [Surface recording of abnormal post-QRS micropotentials. Description and frequency in ventricular tachycardias after myocardial infarction]. AB - In order to study abnormal post-QRS micropotentials, so called late potentials, and to determine their frequency in post myocardial infarction ventricular tachycardia (VT), high amplification electrocardiogrammes were recorded in 180 patients classified in 3 different groups: Group A comprising 36 patients who developed sustained VT after myocardial infarction; Group B comprising 124 patients with myocardial infarction uncomplicated by VT. This group was subdivided into subgroup B1 (retrospective study of 35 patients with chronic myocardial infarction, dating on average 10 months--range 7 days to 8 years) and subgroup B2 (prospective study of 89 patients investigated on the 7th and 60th days after infarction); Group C comprising 20 young, normal control subjects. Using computer assisted high amplification electrocardiography, all patients underwent at least 3 successive recordings of the following parameters: averaging 100 cycles; sampling: 1 kHz; band pass 20-300 Hz and 80-300 Hz; gain setting 10,000 and 25,000. Late potentials usually appears, after the end of the S wave, as high frequency oscillations with an amplitude (10 to 20 microV) significantly greater than that of the background noise. Our recordings also showed: the frequent presence, especially in intraventricular blocks, of fragmentation of the end of the R wave and of the S wave or terminal potentials; the presence of an abnormal giant low frequency high amplitude wave (40 to 80 microV) in 5 patients with a large left ventricular aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103568 TI - [Iatrogenic pathology in coronary intensive care units. Results of a prospective survey on 802 patients]. AB - Iatrogenic disease in the coronary care unit was detected and analysed using a grid over a 17.5 month period (16.09.82 to 25.02.84). The cases of 802 patients, mean age 65.8 years, predominantly male (56.6%) were examined. Minor or minimal pathology in which the causal relationship was conditional or doubtful according to Karch's criteria was excluded. Only those conditions, moderate, severe or even lethal, specific or not to this type of unit, requiring specialised hospital care and in which the causal relationship could be adequately established were retained. Iatrogenic pathology was common: 11.84% of admissions. This group of 95 patients did not differ significantly from a control group with respect to age [average 4 years older (NS)] or mortality. However, there was a clear cut female predominance (68%, p. less than 0.01) and a different distribution of the organic pathology (p less than 0.001). The iatrogenic disease developed before hospital admission in 40% of patients and during hospitalisation in 60% of patients. It increased the duration of the patient's stay by half (2.77 days). Nearly a quarter of these patients had two or more types of iatrogenic disease. The undesirable effects of drugs were mainly bradycardia (44 cases), tachycardia (11 cases), haemodynamic changes, vascular, renal, gastrointestinal, metabolic and endocrine complications. Twenty-one complications of medical procedures and 13 of surgical procedures were also noted. This study, the first to have been performed in a Coronary Care Unit to the author's knowledge, confirms the high incidence of iatrogenic pathology. This fact should be born in mind before taking any therapeutic decision or before performing invasive diagnostic investigations. PMID- 3103569 TI - [Two-dimensional echocardiography in a cardiac intensive care unit]. AB - The increasing number of physicians competent to carry out emergency echocardiography, and the availability of high performance equipment, facilitated the development of this technique in the Coronary Care Unit (CCU). This paper reports our experience of 610 2D echocardiographic recordings performed on 319 patients admitted to the CCU. The quality of the recording was excellent or satisfactory in 67% of cases and mediocre in 30% of cases. In 11 patients (3%) the quality of the recording was too poor to obtain reliable data. In this group of patients, the apical 4-chamber and subcostal views seemed better than the apical 2-chamber and parasternal views. An echocardiographic diagnosis was made in 94% of cases. It contributed to the diagnostic process in 70% of cases. Of the patients studied, 54% were admitted for a recent myocardial infarction. Echocardiography was particularly useful in atypical forms or when the diagnosis was difficult. It was also helpful in detecting complications of recent myocardial infarction, the frequency of which was determined. With respect to other cardiovascular emergencies, echocardiography was determined. With respect to other cardiovascular emergencies, echocardiography was very useful in the diagnosis of dissection of the aorta, pericarditis and for assessing left ventricular function and the causal mechanism in cases of decompensated cardiac failure. The non invasive nature of the investigation allows repeated examination of the patient at the bedside and makes it a particularly valuable technique to monitor the evolution of acute cardiac conditions requiring admission to the Coronary Care Unit. PMID- 3103570 TI - [Continuous electrocardiographic recording with the Holter method in children. Indications and results]. AB - There are relatively few reported studies of continuous electrocardiographic recordings by the Holter method in children. We report our experience of 296 24 hour recordings in 160 patients (average age 10.5 years), investigated for suspected or known cardiac arrhythmias. One hundred and ten patients (68.75%) had no organic heart disease and 6 patients (3.75%) had acquired lesions. Eighty three patients (52%) were symptomatic. Sixty-three patients (39%) had normal recordings; 97 patients (61%) had a total of 126 arrhythmias. There were 45 cases of atrioventricular block, 24 cases of sinus node dysfunction, 39 cases of supraventricular arrhythmias and 18 cases of ventricular arrhythmias. Overall, 47.6% of these rhythm disturbances were diagnosed by Holter monitoring. This technique was particularly valuable in the diagnosis of arrhythmias in symptomatic patients, patients with arrhythmogenic cardiac lesions and in the detection and surveillance of postoperative arrhythmias in congenital heart disease, of pacemakers, of congenital atrioventricular block and of the chronic arrhythmias of childhood. PMID- 3103571 TI - [Coronary stenosis after radiotherapy. Clinical study of 5 cases and review of the literature]. AB - Coronary artery stenosis is one of the possible complications of radiotherapy to the mediastinum. Although less frequent than pericardial disease, anatomopathological studies have shown it not to be uncommon. Five cases with different clinical presentations are reported and the 30 previously described cases are reviewed. Radiotherapy was performed for Hodgkin's disease in 70% of cases and for carcinoma of the breast in 10% of cases. The average delay before onset of the symptoms was 4 years but in some cases delays of up to 10 years were observed. The most common presentation was an inaugural myocardial infarction (50 to 60% of cases). In other cases, angina of effort or typical spastic angina was observed. The coronary lesions were mainly proximal single artery stenosis affecting especially the left anterior descending artery. The typical histological appearances of the stenosis were intimal and sometimes adventicial fibrosis, occasionally associated with medial hyaline sclerosis. However, atherosclerotic lesions were also commonly present. This observation raises the question of the role of irradiation in the development of precocious atherosclerosis by coronary endothelial damage. This hypothesis is supported by the results of experimental studies and by the fact that several autopsy reports showed that the atheroma only developed in the irradiated zone. In addition, although the most demonstrative cases are those of young patients of 30 to 35 years of age, the responsibility of radiotherapy in the development or coronary pathology of older patients cannot be excluded, especially when none of the classical coronary risk factors are present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103572 TI - [Tissue plasminogen activator (t-PA) in myocardial infarction. Biological aspects]. AB - A group of 37 patients with myocardial infarction less than 6 hours old was given 5,000 IU of heparin and 0.75 mg/kg of tissue plasminogen activator (rt-PA) (Group A, N = 18) or placebo (Group B, N = 19) intravenously over 90 minutes in a double blind study. Blood sampling was performed before, during and after treatment. The plasma rt-PA concentrations (micrograms/ml) of Group A were as follows: (Table: see text) The concentrations of plasminogen and antiplasmin have decreased significantly as did the fibrinogen level: a concentration of 1 g/l was observed in 7 cases during rt-PA therapy, lasting for 4 to 8 hours after the end of the infusion of rt-PA in 3 cases. The increase of FDP during rt-PA (m = 551 and 222 micrograms/ml at the 60th and 90th minutes) was relatively moderate considering the average level of defibrination (61%). No significant biological changes were observed in Group B. These results support those of our in vitro trials: at comparable thrombolytic activities, the reduction of plasma fibrinogen is less with rt-PA than with streptokinase (SK) or urokinase (UK). However, at concentrations 1 microgram/ml, rt-PA causes almost complete defibrination. PMID- 3103573 TI - [Arteriovenous fistula disclosing a renal cancer. Apropos of a case]. AB - The authors report the case of a 49 year old woman who presented with congestive cardiac failure and hypertension. Clinical examination revealed a high output state and an abdominal mass with a continuous murmur which angiography showed to be a very vascular right renal tumour with a large and early venous return. Catheter studies confirmed the increased cardiac output (cardiac index 5.37 l/mn/m2), an increase in right heart and mean pulmonary capillary pressures (28 mmHg), decreased peripheral arterial resistances and a left-to-right shunt effect at the level of the suprarenal inferior vena cava (+ 3.8 volumes of oxygen per 100 ml). After radical right nephrectomy, the cardiac failure and hypertension regressed and the haemodynamic parameters returned to normal. PMID- 3103574 TI - [Corrected transposition of the great vessels in aged adults. Apropos of 2 patients aged 72 and 80]. AB - The authors report two unusual new cases of corrected transposition of the great arteries diagnosed in patients 72 and 80 years of age respectively, presenting with symptoms of cardiac failure of recent onset. Both patients had mild or moderate regurgitation of the systemic atrio-ventricular valve, associated in one case with aortic regurgitation. This association would appear to be fortuitous although already reported in six occasions. The diagnosis was made by echocardiography and confirmed by catheterisation in one case, and by digitised intravenous angiography in the other. These cases are of interest for three reasons: They are very rare: there have been only 20 comparable cases reported in patients over 40 years of age, the eldest being 73. This is probably explained by the high frequency of associated malformations. They illustrate the decisive role of echocardiography in the diagnosis of congenital heart disease, even in the adult. They constitute a "natural experimental model" of a right ventricle submitted to systemic pressures and tend to show that, in the absence of other abnormalities giving rise to an additional pressure or volume overload, the right ventricle is capable of long term adaptation to this situation. These observations indicate a favourable long-term prognosis for children who have undergone "corrective" surgery at atrial level for simple transposition and in whom the right ventricle is required to assume the function of the systemic ventricle for the rest of their life. PMID- 3103575 TI - [Double superior vena cava with drainage of the right superior vena cava into the left auricle. Presentation as a cerebral abscess in an adult]. AB - A 44 year old man presented with a cerebral abscess, the location of which suggested a septicaemic origin. Although the patient was not cyanosed, a cardiological work-up was requested to exclude a right-to-left shunt. This showed a double abnormality of the systemic venous drainage: presence of an abnormal left superior vena cava draining into the coronary sinus and of a right superior vena cava draining into the left atrium. These two vena cava intercommunicated by anastomoses. Angiography in the right superior vena cava after occlusion by balloon catheter at its junction with the left atrium showed flow from the right to the left superior vena cava and to the azygos system. Simple ligature of the right superior vena cava was therefore performed to prevent recurrence of cerebral abscess. This case is rare and of interest because of the presence of two superior vena cavae, one on the right draining into the left atrium and the other on the left draining into the coronary sinus, with anastomoses between the two superior vena cavae. This double abnormality of systemic venous drainage explains the absence of cyanosis and therefore the relatively late detection of this malformation. PMID- 3103576 TI - [Familial cardiomyopathy caused by carnitine deficiency]. AB - The authors report a familial case of carnitine insufficiency presenting in two out of seven children as a severe, isolated, hypertrophic and hypokinetic cardiomyopathy. The etiology was confirmed by histological study and measurement of carnitine concentrations in the blood and muscle. The evolution was spectacular with specific therapy. Left ventricular hypokinesia regressed completely within 18 months (fractional fibre shortening increased from 10 to 33% and the SCI from 26 to 55% in the more severe of the two cases). Hypertrophy and dilatation decreased significantly. This is a so-called intermediary form of carnitine insufficiency and very unusual because of the isolated cardiac involvement. These cases underline the value of systematic muscle biopsy with measurement of carnitine concentrations in the investigation of all cases of supposed primary cardiomyopathy, especially as a rapid improvement can be obtained by specific replacement therapy. PMID- 3103577 TI - [Thrombosis of the superior vena cava disclosing Behcet's disease]. AB - The authors report the case of a 29 year old North African patient with Behcet's disease presenting with sudden thrombosis of the superior vena cava. Venous disorders are the fourth major sign of this disease. Although superficial thrombophlebitis is a common presenting sign, caval thrombosis is rare and usually occurs after several years' evolution. Superior vena caval thrombosis may be life threatening due to complications such as pulmonary embolism and haemoptysis. The anatomical substrate of this form of vascular disease is the same as that of the other visceral lesions of Behcet's disease: predominantly venous vasculitis with perivascularitis and secondary thrombosis. The pathogenesis of this thrombotic diathesis is discussed. PMID- 3103578 TI - Accumulation and secretion of exoglucanase activity in yeast secretory mutants. AB - Representative conditional yeast secretory mutants, blocked in transport of secretory and plasma membrane proteins from the endoplasmic reticulum (sec 18), from the Golgi body (sec 7) and in transport of secretory vesicles (sec 1), accumulated exoglucanase, a constitutive yeast activity, when incubated at the restrictive temperature (37 degrees C). Different proportions of the accumulated activity were released by mutant cells under permissive conditions. The presence or absence of cycloheximide during the secretion period made no differences in the results. More than 90% of the internal activity was bound to membrane in wild type cells. However, only the soluble pool underwent changes during the accumulation or secretion periods. The bulk of secretory invertase accumulated by sec 1 was also soluble. By contrast sec 7 and sec 18 accumulated membrane-bound as well as soluble invertase forms and both were secreted in similar proportions in each mutant. More than 90% of the accumulated invertase was secreted at the permissive temperature in sec 18 cells. That percentage was significantly lower for exoglucanase (less than 65%). Concomitantly, invertase accumulated by this mutant exited from the cells with a lower half time (t1/2 = 24 min) than accumulated exoglucanase (t1/2 = 150 min). These results may be interpreted assuming that exoglucanase is exported by a passive flow of the soluble pool. PMID- 3103579 TI - Acetyl-coenzyme A: arylamine N-acetyltransferases in microorganisms: screening and isolation of an enzyme from Bacillus cereus. AB - The raw extracts of a series of microorganisms were screened for the presence of acetyl-coenzyme A: arylamine N-acetyltransferase (AAAT) using a radioactive assay with 3H-acetyl-coenzyme A and aniline as substrates. Enzyme activities were primarily detected in the soluble fractions of Bacillus and Nocardia species, and in some further soil organisms. Only strains of Bacillus cereus were able to acetylate 4-nitroaniline and 3,5-dimethyl-4-nitroaniline. The fermentation conditions for the production of the enzyme were optimized. The AAAT from one strain of Bacillus cereus was purified 24-fold and characterized. PMID- 3103580 TI - A double-blind, placebo-controlled trial of lithium carbonate therapy for alcoholism. AB - The efficacy of lithium carbonate as a treatment for alcoholism was examined in a double-blind, placebo-controlled study of 104 men and women meeting DSM-III criteria for alcohol dependence. Subjects entered the study during inpatient treatment and were subsequently followed up for 12 months. Survival analysis disclosed essentially three categories of treatment response: one for noncompliant subjects (0% to 7% abstinent), one for compliant subjects not attaining therapeutic serum lithium levels (31% to 44% abstinent), and one for compliant subjects with therapeutic serum levels (67% abstinent). Two findings led us to believe that therapeutic serum levels of lithium were associated with better outcome over and above a behavioral compliance effect. First, in a dose response analysis, serum lithium levels and abstinence rates were not linearly associated. Second, all subjects who started lithium carbonate therapy as inpatients were significantly less likely to relapse to drinking during the first month than were placebo-compliant subjects. There was no evidence that depressed alcoholics showed a better treatment response than nondepressed alcoholics or that lithium had any significant impact on the mood or social adjustment of alcoholics. Although the sample size and the difficulties of ascertaining placebo compliance caution against drawing firm conclusions, the data add further support to the hypothesis that lithium has an effect on drinking behavior not related to the treatment of affective symptoms. PMID- 3103581 TI - Distribution of carbonic anhydrase I in gastric and duodenal tissue sections. AB - Forty-four sections of normal and abnormal gastric and duodenal tissue were examined by an immunoperoxidase technique for the demonstration of carbonic anhydrase I. The presence of the enzyme in normal gastric parietal and surface epithelial cells was confirmed. The enzyme was also demonstrated in normal and metaplastic intestinal absorptive cells, and in gastric adenocarcinoma of the usual and superficial types. The enzyme was normally absent in antral and Brunner's glands, normal and metaplastic goblet cells, and signet ring tumor cells. Gastritis and duodenitis were associated with a decrease in the staining intensity of the enzyme in surface epithelial cells, suggesting a possible decreased enzyme activity, which may enhance the risk for peptic ulceration in susceptible persons. PMID- 3103582 TI - Epithelial membrane antigen staining patterns of histiocytic lesions. AB - Epithelial membrane antigen (EMA) appears to be a marker of activation, proliferation, and/or neoplasia in some epithelial and nonepithelial cells, including histiocytes. We performed immunoperoxidase stains for EMA on a variety of histiocytic lesion specimens, including specimens from two cases of interdigitating reticulum cell lymphoma, 12 cases of histiocytosis X, seven cases of sarcoidosis, five cases of granuloma annulare, 13 juvenile xanthogranulomas, two reticulohistiocytomas, five xanthelasmas, three dermatopathic lymph nodes, and three foreign body reactions. Only the two cases of interdigitating reticulum cell lymphoma and two of the 12 cases of histiocytosis X exhibited significant EMA positivity. These findings may prove useful in the differential diagnosis of histiocytic lesions. PMID- 3103583 TI - Transperitoneal absorption of glucose and amino acids for nutritional support. AB - To evaluate the peritoneal membrane as an absorptive surface for nutritional support, 14 New Zealand rabbits with peritoneal catheters were rapidly infused with 75 mL/kg of a 5% glucose and 2.5% mixed amino acid solution. Plasma and peritoneal fluid glucose, amino acid, and electrolyte concentrations and osmolarities were measured serially for six hours following infusion, and nutrient absorptions were calculated. Plasma osmolarity rose minimally, peritoneal fluid osmolarity declined rapidly, and there was a small increase in peritoneal fluid volume. Peritoneal fluid concentrations of glucose and amino acids fell precipitously during the initial two hours, while plasma concentrations rose in reciprocal fashion. Two thirds of the glucose and 83% of the amino acid loads were absorbed at six hours, with most of the absorption occurring within the first two hours. Amino acid absorption was independent of molecular weight and configuration. While glucose and amino acids were rapidly absorbed in adequate amounts, an intraperitoneal nutrition support system will require fat to provide total energy needs. PMID- 3103584 TI - [Activity of and requirement for selected amino acids in growing female pigs. 1. Lysine]. AB - In N balance experiments with a total 59 growing female pigs in the live weight range of 33 to 55 kg the lysine efficiency (bc-1 value) and the lysine efficiency coefficient (kLys) of various cereal proteins were ascertained under the consideration of various charges and varieties. The range of kLys = 0.65 ... 0.96 shows a wide spectrum of lysine efficiency, which results in an analogous differentiation of the derived lysine requirement values. Assuming kLys = 1.0 (lysine efficiency 100%, i.e. the maximum value for bc-1 found as yet for native proteins) a daily lysine requirement (efficient amino acid) of 8.9, 10.8 and 12.6 g resp. was ascertained for 100 g daily protein retention at 30, 40 and 50 kg live weight resp. PMID- 3103585 TI - Glutathione conjugation of chlorobenzylidene malononitriles in vitro and the biotransformation to mercapturic acids in rats. AB - The glutathione conjugation of 2-chloro-, 3-chloro-, 4-chloro- and 2,6 dichlorobenzylidene malononitrile (chloroBMNs) was investigated in vitro. In incubation mixtures containing rat liver cytosol (9000 g), the decrease in the initial amount of glutathione due to the various chloroBMNs ranged from 40 to 60% and occurred both enzymatically and spontaneously at physiological conditions (37 degrees C, pH 7.4). 2,6-DichloroBMN, however, depleted glutathione largely spontaneously (38 +/- 3%). The steric hindrance of the two chlorosubstituents probably plays an important role during the glutathione-S-transferase catalyzed reaction. The hydrolysis of the chloroBMNs to the corresponding chlorobenzaldehydes and malononitrile was studied in a mixture of buffer pH 7.4 and ethanol. The rate of hydrolysis of 2,6-dichloroBMN was slower than those of the related chloroBMNs. This means that 2,6-dichloroBMN will be the most stable compound in the presence of water. Only IP administration of 2-chloroBMN (CS) to adult male Wistar rats gave enhancement of urinary thioether excretion. A thioether could be isolated and was identified as the N-acetyl-S-[2-chlorobenzyl] L-cysteine. The quantity of this benzylmercapturic acid in the urine of rats amounted to 4.4% dose (0.07 mmol/kg, n = 12). After IP administration of 2-chloro and 3-chlorobenzaldehyde to rats benzylmercapturic acid excretion in the urine was found to be 7.6 and 1.1% of the dose, respectively. Administration of the related 4-chloro- and 2,6-dichlorobenzaldehyde, however, resulted in no urinary mercapturic acid excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103586 TI - [Delayed-type hypersensitivity to sheep red blood cell in mice infected with Mycoplasma pulmonis]. PMID- 3103587 TI - Forced normalization. Acute psychosis after seizure control in seven patients. AB - An antagonistic relationship between psychosis and seizures has been described in some patients and is sometimes termed "forced normalization." We saw seven epileptic patients without a previous psychiatric history, who developed acute psychotic states on establishment of seizure control and normalization of previously abnormal electroencephalograms with frank epileptiform activity. A possible hypothetical relationship between psychosis and epilepsy regarding the mesolimbic dopaminergic system and kindling of this system with epileptic discharge in temporal-limbic circuits could induce a florid psychotic state in some patients. This biochemical relationship to schizophrenia with heightened dopamine activity would also easily explain the amelioration of acute psychotic activity in our seven patients with neuroleptic agents and their antagonism of this increased dopaminergic outflow state. PMID- 3103588 TI - Rieger's anomaly and glaucoma associated with partial trisomy 16q. Case report. PMID- 3103589 TI - Posttraumatic Bacillus cereus endophthalmitis. AB - We encountered a patient who developed Bacillus cereus endophthalmitis following trauma. Early therapy, which included intravitreal clindamycin phosphate and gentamicin sulfate, resulted in a visual acuity of 20/60. A five-year retrospective review of all cases of endophthalmitis following trauma reported at our institution revealed Bacillus as the infecting organism in six (46%) of 13 culture-positive cases. The high frequency of virulent Bacillus infections in the setting of trauma necessitates the use of antibiotics that are active against this organism in posttraumatic endophthalmitis. The combination of clindamycin and gentamicin can be effective therapy in Bacillus species infections if used early in the course of the disease. PMID- 3103590 TI - Maternal serum diamine oxidase activity in the third trimester. PMID- 3103591 TI - The acute effects of antidepressants, maprotiline and amoxapine on serum prolactin and gonadotropin levels in normal women. PMID- 3103592 TI - Characteristics of anticellular activities of human recombinant interferon gamma on gynecological malignancies: in vitro sensitivity. PMID- 3103593 TI - Answers to common questions about DRGs. PMID- 3103594 TI - The relationship of nutritional parameters to mortality and septic complications. AB - The relationship of a number of nutritional parameters to mortality and sepsis was assessed in a group of 82 patients requiring total parenteral nutrition (TPN). Duration of TPN ranged from 9 to 105 days with a mean of 32.3 days. Parameters assessed were serum albumin, transferrin, absolute lymphocyte count (ALC), delayed hypersensitivity skin test reaction, mid-arm muscle circumference, triceps skin-fold thickness and weight. Combinations of parameters were found to be more useful than single parameters. The only single parameter of significance was ALC. The best overall predictor of death and/or sepsis was a combination of reduced serum albumin, transferrin, ALC and anergy, which was found to be related to a significantly higher mortality (P = 0.002) and incidence of septic complications (P = 0.003). This combination of parameters also had the best specificity (90%), accuracy (79%) and positive predictive value (65%) for prediction of death and/or sepsis. Increasing age was also found to be associated with a higher mortality (P less than 0.001) and increased incidence of septic complications (P = 0.01). PMID- 3103595 TI - Home parenteral nutrition: Westmead Hospital experience. AB - Home parenteral nutrition (HPN) has been used in 13 patients over a 7 year period for intervals ranging from 14 to 608 days with a mean of 255 days. This represents a total experience of 3315 patient days or 9.1 patient years. The commonest causes for intestinal failure requiring HPN were short bowel syndrome following massive small bowel resection for mesenteric ischaemia (four patients), and radiation enteritis (three patients). Four patients died, including three of four who had presented with mesenteric ischaemia and one from disseminated malignancy. One of the deaths was from massive pulmonary embolus and may have been catheter-related. Seven patients were able to cease HPN after a mean of 200.7 days because of treatment and/or improvement in the underlying cause of their intestinal failure. Central venous thrombosis was the commonest complication and occurred in six patients, including the four who died. PMID- 3103596 TI - Immunoreactivity of fractionated antigens obtained from autoclaved extracts of an arthritogenic isolate of Erysipelothrix rhusiopathiae. AB - The immunoreactive antigens in heat-extracted (autoclaved) preparations of an arthritogenic strain of Erysipelothrix rhusiopathiae (isolate VRS 229, serotype 1a) have been identified by gel diffusion precipitin (GDP) tests and a novel application of the enzyme linked immunosorbent assay (ELISA) procedure. Antigens precipitated by ethanol treatment of autoclaved extracts of this strain were resolved into 4 major peaks (A,B,C and D) after gel permeation chromatography on Sephacryl S200. Peak A was confirmed as a protein peak (Lowry positive) which was excluded from the gel. This peak was identified to be ELISA-reactive when assayed with serum from pigs infected with other isolates corresponding to serotypes 1a, 1b and 2. However, it did not form precipitin lines in GDP tests. Peak B was Lowry-positive and also contained carbohydrates. It was not as reactive in ELISA tests but rapidly formed precipitin lines with serum from pigs infected with the homologous isolate, but only erratically with serums from pigs infected with other serotype 1a and 1b isolates, and not with serotype 2 isolates. Peaks C and D were high in carbohydrate and phosphate content respectively but were both non reactive in GDP tests and only slightly so by ELISA. Since serotypes 1 and 2 are the most predominant among isolates from infected pigs it is likely that the commonly recognised A antigen is a useful ELISA reagent for the diagnosis of E. rhusiopathiae infection; B antigen on the other hand, would probably be of limited diagnostic value. PMID- 3103597 TI - Acute intoxication of marmosets and rats fed high concentrations of the dietary antioxidant "ethoxyquin 66". PMID- 3103598 TI - Immunohaematological testing of the antenatal patient. Is the Rh(D) positive woman as important as the Rh(D) negative woman? AB - During a 4-year period postnatal samples referred for testing for anti-Rh(D) immunoglobulin eligibility were analysed for irregular red cell antibodies. Fifty two (2%) of 2,600 samples received contained antibodies to a variety of red cell antigens. Twenty four (46%) of these antibodies were undiagnosed prior to term and were a chance finding only on postnatal testing. Eleven of these latter antibodies (45%) had the potential for neonatal morbidity. The frequency of antenatal testing is discussed in relation to the Rh(D) positive as well as the Rh(D) negative woman. PMID- 3103599 TI - Urethral diverticulum. PMID- 3103600 TI - An unusual case of rhesus isoimmunization. AB - A case of rhesus isoimmunization with spontaneous improvement in severity of erythroblastosis with advancing parity is presented. The isoimmunized pregnant woman after having 3 perinatal deaths all due to severe hydrops fetalis, subsequently delivered 2 Rh-positive surviving infants. In her last pregnancy, the timing of delivery was indicated by cessation of fetal movements, followed by a sinusoidal fetal heart rate pattern. The newborn, needing 5 exchanging blood transfusions, subsequently did well. PMID- 3103601 TI - Rapid inactivation of the plasminogen-activator inhibitor upon secretion from cultured human endothelial cells. AB - In conditioned medium (CM) from cultured human endothelial cells, two forms of plasminogen-activator inhibitor (PA-inhibitor) can be demonstrated: a fast-acting active form and an immunologically related, inactive form. Evidence is presented that endothelial cells produce active PA-inhibitor which is rapidly inactivated upon secretion into the medium. This inactivation can, at least partly, be prevented by culturing cells with excess of tissue-type plasminogen activator (t PA). This results in the formation of large amounts of t-PA-PA-inhibitor complex at the cost of accumulation of inactive PA-inhibitor. No complex was detectable when inactive PA-inhibitor preparations were incubated with t-PA either in the absence or in the presence of cells. Furthermore, in cell extracts, predominantly functionally active PA-inhibitor was present. PA-inhibitor derived from the t-PA PA-inhibitor complex showed an Mr approx. 4000 lower by polyacrylamide-gel electrophoresis than that of the inactive form. The rapid inactivation seems to be confined to newly synthesized molecules, since PA-inhibitor molecules in CM are inactivated much more slowly (even with cells or cell homogenates) than necessary to explain the excessive production of inactivated PA-inhibitor by cells. It could not be prevented by inhibitors of oxidative processes, like butylated hydroxytoluene, dithiothreitol, superoxide dismutase and catalase. PMID- 3103602 TI - An inhibitory role for the protein kinase C pathway in ovarian steroidogenesis. Studies with cultured swine granulosa cells. AB - We have used primary cultures of swine granulosa cells to investigate the regulatory role of the protein kinase C pathway in the ovary. In this system, we observed the following. Swine granulosa cells bound [3H]phorbol 12,13-dibutyrate [( 3H]PDB) specifically with high affinity [apparent Ki for 12-O tetradecanoylphorbol 13-acetate (TPA) = 3.1 (2.1-4.7) nM] and low capacity [0.68 (0.34-0.99) pmol/10(7) cells]. The cytosol of granulosa cells contained functionally active protein kinase C capable of phosphorylating distinct proteins in response to stimulation with active phorbol ester. TPA and PDB induced dose dependent inhibition (greater than 85%) of follicle-stimulating-hormone (FSH) stimulated progesterone production. Half-maximally inhibitory concentrations were 0.10 and 0.75 nM for TPA and PDB respectively, whereas phorbol analogues that do not activate protein kinase C were not inhibitory. TPA did not impede cyclic AMP generation in response to FSH, cholera toxin or forskolin acutely (within 48 h), but did inhibit the stimulatory effects of 8-bromo cyclic AMP, insulin and oestradiol on progesterone biosynthesis. In the presence of maximally effective concentrations of 25-hydroxy-, 20 alpha-hydroxy- or 22R-hydroxy-cholesterol as exogenous sterol substrates for cholesterol side-chain cleavage, treatment with TPA suppressed pregnenolone, progesterone and 20 alpha-hydroxypregn-4-en-3-one biosynthesis by more than 80%. The inhibitory effects of phorbol esters were not attributable to non-specific cytotoxicity, since prostaglandin F2 alpha production increased in the same cultures and aromatization of exogenously supplied testosterone to oestradiol was not suppressed. In intact granulosa cells, the effects of phorbol esters were mimicked by a synthetic non-diterpene diacylglycerol, 1-octanoyl-2-acetylglycerol, and the tumour promoter, mezerein, which specifically activates protein kinase C. We conclude that swine granulosa cells contain specific high-affinity receptors for phorbol esters that are functionally coupled to protein phosphorylation. Moreover, treatment with phorbol esters or non-phorbol activators of protein kinase C results in selective inhibition of cholesterol side-chain cleavage activity without impairing cyclic AMP generation or oestrogen biosynthesis. PMID- 3103603 TI - Structural studies of a carbohydrate-containing immunoglobulin-lambda-light-chain amyloid-fibril protein (AL) of variable subgroup III. AB - The amino acid sequence of the variable region of a carbohydrate-containing amyloid-fibril protein MOL of immunoglobulin-light-chain type (AL) was elucidated. The sequence determination involved cleaving the protein with CNBr, BNPS-skatole, thermolysin and trypsin. The sequenced protein consisted of about 130 amino acid residues; however, gel-filtration and N-terminal analysis studies revealed AL proteins ranging in Mr from about 10,000 to 25,000. The oligosaccharide chain was found to be bound in the hypervariable region. By sequence homology to other lambda chains the AL protein MOL was shown to be of the V lambda III subgroup. PMID- 3103604 TI - Modulation of lipid fluidity of small- and large-intestinal antipodal membranes by Ca2+. AB - A series of experiments were conducted to examine the role of Ca2+ in modulating the fluidity of rat small- and large-intestinal antipodal plasma membranes and their liposomes. This bivalent cation was found to decrease the fluidity of these preparations in a complex manner involving at least two distinct mechanisms. The first appeared to be a direct effect of Ca2+ on fluidity, was readily reversible by addition of EGTA and presumably involved binding of Ca2+ to anionic sites in the lipid bilayers of these membranes. This effect was seen with all preparations examined. In contrast, the second effect of Ca2+ on fluidity was only seen in intact small-intestinal brush-border membranes, appeared to be indirect, was time and cation-dependent, was only minimally reversible by addition of EGTA, and appeared to involve stimulation of membrane-bound enzymes which altered this membrane's fatty acid composition. Furthermore, regional differences in this latter effect of Ca2+ on brush-border membrane fluidity were also seen in these studies, i.e. proximal greater than distal small intestine. PMID- 3103605 TI - Diacylglycerol induces deacylation of phosphatidylinositol and mobilization of arachidonic acid in mouse macrophages. Comparison with induction by phorbol diester. AB - 1,2-Dioctanoyl-sn-glycerol (2-50 microM) was found, like phorbol myristate acetate (greater than or equal to 3 nM) to stimulate phospholipase A-type cleavage of phosphatidylinositol and the release of arachidonic acid from macrophage phospholipids. The 1,3 isomer of dioctanoylglycerol was inactive, whereas racemic 1,2-dioctanoylglycerol was half as potent as the 1,2-sn enantiomer. Dioctanoylglycerol-induced deacylation of phosphatidylinositol was only partly dependent on extracellular calcium but was more severely inhibited by depletion of intracellular calcium. Chlorpromazine inhibited the deacylation of phosphatidylinositol, whereas inhibitors of cyclo-oxygenase and lipoxygenase were ineffective. Since both phorbol myristate acetate and 1,2-dioctanoyl-sn-glycerol are known to activate protein kinase C, the results suggest that this kinase is involved in the sequence of events leading to release of arachidonic acid in macrophages. PMID- 3103606 TI - Phenotyping of human complement component C4, a class-III HLA antigen. AB - The plasma complement protein C4 is encoded at two highly polymorphic loci, A and B, within the class-III region of the major histocompatibility complex. At least 34 different polymorphic variants of human C4 have been identified, including non expressed or 'null' alleles. The main method of identification of C4 polymorphic allotypes is separation on the basis of charge by agarose-gel electrophoresis of plasma. On staining by immunofixation with anti-C4 antibodies, each C4 type gives three major bands, but, since individuals can have up to five allotypes, the overlapping banding pattern is difficult to interpret. We show that digestion of plasma samples with carboxypeptidase B, which removes C-terminal basic amino acids, before electrophoresis, produces a single, sharp, distinct band for each allotype and allows identification of the biochemical basis of the multiple banding pattern previously observed in C4 phenotype determination. PMID- 3103607 TI - Strain differences in the maintenance of cytochrome P-450 and mixed-function oxidase activities in cultured rat hepatocytes. Effect of prostaglandins. AB - The mixed-function-oxidase (MFO) activities, ethoxyresorufin and pentoxyphenoxazone O-dealkylase, of cultured Hooded-Lister(HL)-rat hepatocytes declined rapidly during 72 h of culture, whereas in Sprague-Dawley(SD)-rat hepatocytes the MFO activities increased between 24 and 72 h in culture. Cytochrome P-450 content declined at the same rate in both HL- and SD-rat hepatocyte cultures. NADPH:cytochrome c reductase and NADH:cytochrome b5 reductase were more stable in SD- than in HL-rat hepatocyte cultures. 16,16 Dimethylprostaglandins E2 and F2 alpha improved the maintenance of cytochrome P 450 content, MFO activity and NADPH:cytochrome c reductase in the HL-rat hepatocyte cultures. In SD-rat hepatocytes, the prostaglandins had no effect on cytochrome P-450 content or NADPH:cytochrome c reductase activity, whereas they prevented the increase observed in MFO activities between 24 and 72 h after culture. PMID- 3103608 TI - Role of ATP and enzyme-bound nascent peptides in the control of elongation for mycobacillin synthesis. AB - The enzyme fraction A, a constituent of the three-fraction (A, B and C) enzyme complex mycobacillin synthetase, elongated tri- and tetra-peptides, under enzyme bound conditions, to tetra- and penta-peptides respectively in the presence of the 'next' amino acid (in the mycobacillin sequence). The enzyme fraction B synthesized hexapeptide from free pentapeptide and the next amino acid, but synthesized heptapeptide from hexapeptide only under enzyme-bound conditions in the presence of the next amino acid. Similarly, the enzyme fraction C synthesized decapeptide from free nonapeptide in the presence of the next amino acid, but undecapeptide only from enzyme-bound decapeptide in the presence of the next amino acid during the elongation process. The Km values for the initiating reactions for each of the three enzyme fractions were 6-7-fold lower than those for the succeeding reactions catalysed by each of the enzyme fractions. The specificity of the initiation and elongation is discussed in the light of these findings. PMID- 3103609 TI - Effect of fructose 1-phosphate on the activation of liver glycogen synthase. PMID- 3103611 TI - Characterization of bovine kappa-casein fractions and the kinetics of chymosin induced macropeptide release from carbohydrate-free and carbohydrate-containing fractions determined by high-performance gel-permeation chromatography. AB - Bovine kappa-casein was fractionated at pH 8.0 on DEAE-Sepharose with an NaCl gradient, followed by DEAE-cellulose chromatography using a decreasing pH gradient from pH 6.0 to 4.5. At least ten components could be identified, each differing in N-acetylneuraminic acid (NeuAc) and/or phosphorus content. Two components appeared to be multiply-phosphorylated, but did not contain NeuAc. The possible significance of this finding in relation to the mode of phosphorylation and glycosylation in vivo is discussed. A carbohydrate-free fraction as well as two NeuAc-containing fractions were compared in their substrate behaviour towards the action of the milk-clotting enzyme chymosin at pH 6.6 and 30 degrees C. To this end the trichloroacetic acid-soluble reaction products were analysed by high performance gel-permeation chromatography. In order of increasing carbohydrate content the kcat. values found ranged from 40 to 25 s-1 and the Km values from 9 to 3 microM; the overall substrate properties of these components as reflected by the kinetic parameter kcat./Km ranged from 5 to 8 microM-1 X S-1. Irreversible polymerization of the carbohydrate-free fraction brought about a more-than-2-fold increase in Km, the kcat. value remaining virtually constant. The kcat./Km found for the cleavage of whole kappa-casein at pH 6.6 was of the same magnitude as the kcat./Km found for the polymerized carbohydrate-free fraction (i.e. about 3 microM-1 X S-1). No indication of substrate inhibition was found for the carbohydrate-free fraction. PMID- 3103610 TI - G-proteins of fat-cells. Role in hormonal regulation of intracellular inositol 1,4,5-trisphosphate. AB - Pertussis toxin abolishes hormonal inhibition of adenylate cyclase, hormonal stimulation of inositol 1,4,5-trisphosphate accumulation in rat fat-cells, and catalyses the ADP-ribosylation of two peptides, of Mr 39,000 and 41,000 [Malbon, Rapiejko & Mangano (1985) J. Biol. Chem. 260, 2558-2564]. The 41,000-Mr peptide is the alpha-subunit of the G-protein, referred to as Gi, that is believed to mediate inhibitory control of adenylate cyclase by hormones. The nature of the 39,000-Mr substrate for pertussis toxin was investigated. The fat-cell 39,000-Mr peptide was compared structurally and immunologically with the alpha-subunits of two other G-proteins, Gt isolated from the rod outer segments of bovine retina and Go isolated from bovine brain. After radiolabelling in the presence of pertussis toxin and [32P]NAD+, the electrophoretic mobilities of the fat-cell 39,000-Mr peptide and the alpha-subunits of Go and Gt were nearly identical. Partial proteolysis of these ADP-ribosylated proteins generates peptide patterns that suggest the existence of a high degree of homology between the fat-cell 39,000-Mr peptide and the alpha-subunit of Go. Antisera raised against purified G proteins and their subunits were used to probe immunoblots of purified Gt, Gi, Go, and fat-cell membrane proteins. Although recognizing the 36,000-Mr beta subunit band of Gt, Gi, Go and a 36,000-Mr fat-cell peptide, antisera raised against Gt failed to recognize either the 39,000- or the 41,000-Mr peptides of fat-cells or the alpha-subunits of Go and Gi. Antisera raised against the alpha subunit of Go, in contrast, recognized the 39,000-Mr peptide of rat fat-cells, but not the alpha-subunit of either Gi or Gt. These data establish the identity of Go, in addition to Gi, in fat-cell membranes and suggest the possibility that either Go or Gi alone, or both, may mediate hormonal regulation of adenylate cyclase and phospholipase C. PMID- 3103612 TI - Influence of temperature on the enzymic semisynthesis of human insulin by coupling and transpeptidation methods. AB - The influence of temperature of enzymic semisynthesis of human insulin ester was determined by using coupling and transpeptidation methods with trypsin and Achromobacter lyticus proteinase I as catalysts. The optimal reaction conditions were studied at the selected temperatures of 25, 12 and 4 degrees C. The results showed that the synthesis rates by both methods with trypsin increased as the temperature increased, but the final product yield correspondingly decreased. Therefore the reaction with trypsin should be done below 12 degrees C, preferably at 4 degrees C. This agrees well with the stability of trypsin at these temperatures. When the catalyst was Achromobacter lyticus proteinase I, no such complex temperature effects were observed, and the findings indicated that the reactions should be conducted below 37 degrees C for enzyme stability. PMID- 3103613 TI - Inhibition of poly(ADP-ribose) synthetase potentiates cell dacarbazine cytotoxicity. AB - Dacarbazine induces DNA lesions in cells synthesizing new DNA. When poly(ADP ribosylation) is inhibited with 3-aminobenzamide, repair of the dacarbazine induced DNA lesions is reduced. This is parallelled by increased cytotoxicity. Cells pre-treated with aphidicolin (to stop DNA synthesis) are resistant to dacarbazine. PMID- 3103614 TI - Modulation of ryanodine-induced Ca2+ release in amphibian skeletal muscle. AB - We examined effects of ryanodine on tension in intact and skinned amphibian skeletal muscle. 100 microM ryanodine (RY) alone in the frog Ringer's solution (FR) produced tension in the intact muscle reaching its peak by 1 h; 10 min treatment with RY augmented depolarization-induced tension and prevented a subsequent caffeine-induced contraction. In contrast, RY in Ca2+-free FR was unable to produce tension, after which caffeine produced irreversible tension. In skinned fibers, RY at pCa 6.5 produced tension and abolished a subsequent caffeine-induced contraction; while Ry in 2 mM EGTA did not produce tension. These data indicate that RY, in the presence of CA2+, releases CA2+ from the SR resulting in subsequent depletion of CA in the SR. PMID- 3103615 TI - Polyamines and diamine oxidase activity in maternal, embryonal, and fetal tissues of rat after chronic ethanol consumption. AB - The effects of maternal ethanol consumption for 4 weeks before and throughout gestation on polyamine content and diamine oxidase activity of maternal, embryonal and fetal tissues are reported. At the 12th day of pregnancy, a decrease of putrescine in the liver of the mother and marked increases in putrescine, cadaverine and spermidine in embryos were observed. At day 18, putrescine and cadaverine diminished in maternal liver and placenta, and no changes in amine content in fetal liver and brain were found. At day 12, diamine oxidase activity increased in maternal liver and placenta, whereas it greatly diminished in embryos. At day 18, enzyme activity decreased in maternal liver, placenta, fetal liver and brain. These results indicate that chronic ethanol ingestion induces alterations in polyamine concentrations and metabolism in growing and developing tissues during pregnancy that might contribute to the adverse effect of ethanol on conceptual development. PMID- 3103616 TI - Aflatoxin B1-4-hydroxylase is associated with cytochrome P3-450 in C57BL/6 mouse liver. AB - Messenger RNA from the livers of Aroclor 1254 treated mice was used to produce a cDNA library. cDNA clones corresponding to cytochromes P1-450 and P3-450 were isolated from this library by screening with a probe for the rat cytochrome P 450c gene. Specific non-cross hybridizing probes for P1-450 and P3-450 were prepared from unique restriction fragments. The radiolabeled probes were hybridized to RNA from mice treated with a low (15 mg/kg) and high (150 mg/kg, 400 mg/kg) doses of beta-naphthoflavone. The low dose of beta-naphthoflavone was found to induce only P3-450 mRNA, whereas higher doses induced both P1-450 and P3 450 mRNA. Similarly, a low dose of beta-naphthoflavone induced aflatoxin B1-4 hydroxylase, whereas higher doses induced both aflatoxin B1-4-hydroxylase and aryl hydrocarbon hydroxylase activities. These results suggest that P3-450 mRNA codes for the cytochrome that is associated with aflatoxin B1-4-hydroxylase activity. PMID- 3103617 TI - The rabbit differs from other mammalian in the tissue distribution of alkaline phosphatase isoenzymes. AB - There are only two gene loci code for alkaline phosphatase of mammalian other than human and great apes: one for the intestinal form and other for the liver/kidney/bone form. The former form is present only in the intestine and the latter form occurs in other tissues such as liver, kidney and bone. In the present study, the rabbit was found to be different from other mammalian in the tissue distribution of alkaline phosphatase isoenzymes: only in the rabbit, most of the enzyme in the kidney and liver was the third form which differs from the liver/kidney/bone form, and this form was enzymatically and immunologically similar to the intestinal form of ALPase. PMID- 3103618 TI - Translocation of protein kinase C is not required to inhibit the antigen-induced increase of cytosolic calcium in a mast cell line. AB - Cross-linking of receptor bound IgE antibodies by multivalent antigen (DNP8-BSA) on PB-3c cells leads to an increase of cytosolic calcium ((Ca2+)i). Active tumor promoting phorbol esters and teleocidin which specifically activate the phospholipid Ca2+-sensitive protein kinase (PKC), inhibited the antigen-mediated rise in (Ca2+)i and induced a time and dose-dependent translocation of cytosolic PKC to membranes of the PB-3c cells as determined by enzyme activity or immunoblotting using a polyclonal anti-PKC antibody. This TPA concentration did not affect the subcellular distribution of PKC, although 1 nM of 12-O tetradecanoylphorbol-13-acetate (TPA) inhibited to 50% the antigen-mediated increase in (Ca2+)i. The concentration of TPA required to induce a half-maximal subcellular redistribution of immunodetectable PKC activity was an order of magnitude greater than the half-maximal dose required to inhibit the antigen mediated increase in (Ca2+)i. These data demonstrate that the TPA-dependent activation of PKC is not directly coupled to its translocation to membranes. PMID- 3103619 TI - Inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity by 1-methyl-4 phenylpyridinium ion. AB - Effect of 1-methyl-4-phenylpyridinium ion (MPP+) on the activity of NADH ubiquinone oxidoreductase was studied using mitochondria prepared from rat brains. At first, inhibition of oxygen consumption by MPP+ with pyruvate + malate or glutamate + malate as substrates was confirmed polarographically using a Clark type oxygen electrode. Then, activity of NADH-ubiquinone oxidoreductase in the same samples used in polarography was assayed. Incubation of mitochondria with 0.05 mM of MPP+ together with glutamate, malate and ADP resulted in approximately 50% inhibition of NADH-ubiquinone oxidoreductase activity. Significance of the results was discussed with respect to the mechanism of neuronal degeneration by MPP+. PMID- 3103620 TI - Cell cycle-dependent potentiation of X-ray-induced chromosomal aberrations by 3 aminobenzamide. AB - The poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide had dramatically different effects on X-ray-induced cytogenetic damage in human lymphocytes depending on the stage of the cell cycle in which cells were irradiated. 3 Aminobenzamide (0.08-3.00 mM) potentiated the frequency of chromosomal aberrations when lymphocytes were irradiated in G1, S, or late G2. No effect was observed, however, when lymphocytes were irradiated in G0 or at the S/G2 boundary 6 h before termination of culture. These results indicate that poly(ADP-ribose) polymerase may be involved in chromosomal repair of radiation damage only during specific stages of the cell cycle. PMID- 3103621 TI - Gamma interferon inhibits basal and interleukin 1-induced prostaglandin production and bone resorption in neonatal mouse calvaria. AB - Production of the osteolytic arachidonic acid metabolites, prostaglandin (PG) E2, PGI2 and PGF2 alpha, by neonatal mouse calvariae was quantitated by gas chromatography/mass spectrometry. Mouse recombinant interleukin 1 (rIL-1) raised medium levels of PGE2 and PGI2 (measured as 6-keto-PGF1 alpha) in the dose range tested (1.0-10.0 U/ml culture medium), while an effect on PGF2 was only observed at 10 U/ml. Bone resorption in response to rIL-1 reached a plateau at 3.0 U/ml. Mouse recombinant gamma-interferon (rIFN-gamma) between 100-500 U/ml suppressed basal PG synthesis and spontaneous resorption of cultured bone. In addition, IFN gamma at 100 U/ml prevented stimulation of PG synthesis by 3.0 U/ml rIL-1 and thereby reduced the bone resorbing activity of the cytokine by at least 60%. 5 X 10(-7) M indomethacin was equally effective in suppression of PG synthesis and bone resorption. The present study provides evidence that IFN-gamma inhibits PG synthesis and consequently resorption of cultured bone. PMID- 3103622 TI - The rates of fast reactions of carbon dioxide and bicarbonate in human erythrocytes measured by carbon-13 NMR. AB - The application of carbon-13 nuclear magnetic resonance spectroscopy to the study of the kinetics of millisecond timescale reactions of CO2 in human erythrocyte suspensions is described. The rates of intracellular enzyme catalyzed CO2 hydration and HCO3- dehydration were quantitatively determined, as well as the rates of CO2 diffusion into and out of the erythrocytes. The method also provides an accurate measure of the intracellular pH in the range of pH 6.0 to pH 7.0. A temperature dependence study was used to determine the thermodynamic functions for the intracellular hydration-dehydration reaction. PMID- 3103623 TI - Rapid mechanical changes in the amphibian retina evoked by brief light pulses. AB - Dark-adapted retinae of the toad and bullfrog were found to respond to brief light stimuli with a succession of rapid mechanical changes. The latencies of the mechanical responses, as well as the effects of chemicals known to block the synapses on photoreceptor cells, indicate that the first mechanical response represents swelling of the photoreceptor cells. The first response is followed by mechanical changes in the postsynaptic elements. It is suggested that the observed response of the photoreceptor cells is a mechanical expression of the process underlying heat production by the cells. PMID- 3103624 TI - Mechanism of antitumoral activity of catechols in culture. AB - Cell lines Raji and K 562, lacking tyrosinase, and two melanotic human melanoma cell lines (IRE 1 and IRE 2), were exposed to concentrations from 5 X 10(-3) M to 10(-5) M of different phenols which are substrates of tyrosinase, i.e. l-dopa, dopamine, hydroquinone, terbutylcatechol, and of phenols which are not substrates of the tyrosinase, i.e. resorcinol, butylated hydroxyanisole and hydroquinone dimethyl ether. Cultures were carried out in the presence or in the absence of oxygen radical scavenger enzymes superoxide dismutase, catalase and peroxidase. The stability of each substance in culture medium was assayed by high performance liquid chromatography (HPLC). Results showed that: catechols which are substrates of tyrosinase decompose fully after 24 hr in medium; they are equally toxic for melanoma and non-melanoma cell lines; their toxicity increases when they are preincubated in medium for 24 hr and 48 hr before addition of cells; their toxicity is significantly reduced by addition of scavenger enzymes; on the contrary, phenols not substrates of tyrosinase are stable in medium and their toxicity is not reduced by scavenger enzymes. It is concluded that tyrosinase does not play a major role in catechol toxicity in vitro, which is probably due to some products of catechol decomposition, especially oxygen radicals, acting outside the cells. PMID- 3103625 TI - Pharmacological modulation of eicosanoid levels and hyperalgesia in yeast-induced inflammation. AB - Injection of brewer's yeast into the rat paw results in edema and a subsequent hyperalgesia. The edema was accompanied by an increase in 5-lipoxygenase products, and the hyperalgesia coincided with the formation of both cyclooxygenase and 5-lipoxygenase products. When administered perorally, indomethacin inhibited cyclooxygenase product formation, phenidone inhibited 5 lipoxygenase product formation, and 3-amino-1-(m-[trifluoromethyl]-phenyl)-2 pyrazoline (BW 755C) inhibited formation of products of both pathways. These compounds were also effective analgesic agents. The correlation of these effects with the suppression of hyperalgesia suggests the participation of products from both cyclooxygenase and 5-lipoxygenase pathways in the mediation of hyperalgesia. PMID- 3103626 TI - Trypanosoma cruzi adenine nucleoside phosphorylase. Purification and substrate specificity. AB - An adenine nucleoside phosphorylase has been partially purified from extracts of epimastigotes of the Peru strain of Trypanosoma cruzi, the causative agent of Chagas' disease. The purification procedure separated this enzyme from the three other nucleoside-cleaving enzymes found in extracts. The adenine nucleoside phosphorylase, which efficiently cleaved 5'-deoxy-5'-methylthioadenosine (MTA), had a particle weight of 68,000 and exhibited a broad pH optimum between pH 6 and 8. In addition to MTA, the purified enzyme cleaved and synthesized adenosine and 2'-deoxyadenosine with high efficiency. This contrasts to the enzyme from S-180 cells which has been reported to cleave adenosine poorly and not to cleave 2' deoxyadenosine. Several observations suggested that the three substrates, MTA, adenosine and 2'-deoxyadenosine, use a common catalytic site: (a) all served as alternate-substrate inhibitors exhibiting mutually competitive inhibition with Ki values equivalent to their respective Km values, (b) 5'-chloroformycin A exhibited a competitive Ki value of 4 microM with each nucleoside substrate, and (c) the Km value of phosphate derived from initial velocity studies (180 +/- 20 microM) was independent of the nucleoside substrate. Substrate specificity studies in both the synthesis and cleavage direction indicated that the enzyme had a broad specificity for bases and nucleosides. For the synthesis of nucleosides, the enzyme demonstrated a preference for an amino group in the position equivalent to the 6 position of purine. Compounds containing a hydroxyl group in this position were not substrates. Although a hydrogen or methyl group could substitute for a 6-amino group, a marked decrease in substrate efficiency was observed with these compounds. Alterations in the purine ring led to decreases in the maximal velocity values as evidenced by the substrate or nonsubstrate properties of 1-, 3-, and 7-deazaadenine and 4-aminopyrazolo[3,4 d]pyrimidine. The Km values for 5-methylthioribose 1-phosphate, ribose 1 phosphate and 2'-deoxyribose 1-phosphate with adenine serving as acceptor were 21, 150 and 370 microM. For nucleoside cleavage, the T. cruzi enzyme catalyzed the phosphorolysis of a variety of 5'-substituted adenine-containing nucleosides including those possessing 5'-hydrogen-, hydroxyl-, halogeno-, alkylthio-, amino- and azido-moieties. Inclusion of an ionized group in the 5'-position, such as 5' carboxy-5'-deoxyadenosine or AMP, precluded substrate activity. 3' Deoxyadenosine, arabinosyladenine and alpha-adenosine did not serve as substrates.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3103627 TI - Inhibition of microsomal cytochrome c reductase activity by a series of alpha, beta-unsaturated aldehydes. AB - alpha, beta-Unsaturated aldehydes are reactive and cytotoxic compounds which occur in the environment and are also formed in vivo. Many of these aldehydes have been reported to inhibit hepatic cytochrome P-450. Our laboratory has shown that trans,trans-muconaldehyde (a possible metabolite of benzene) as well as acrolein and crotonaldehyde, when added to hepatic microsomes, decreased cytochrome P-450 (measured spectrophotometrically). Additional studies showed that several alpha, beta-unsaturated aldehydes also inhibited hepatic microsomal NADPH-cytochrome c reductase. Acrolein, crotonaldehyde and trans,trans muconaldehyde all decreased NADPH-cytochrome c reductase activity in vitro. Concentrations of 0.5, 1.0 and 1.5 mM acrolein decreased activity to 60, 26 and 11% of control respectively. Similar concentrations of trans,trans-muconaldehyde inhibited NADPH-cytochrome c reductase. Crotonaldehyde was a less effective inhibitor of this enzyme. Propionaldehyde, a saturated aldehyde, had no effect on NADPH-cytochrome c reductase activity. Time course experiments with acrolein over a period of 5-45 min suggest that the loss of NADPH-cytochrome c reductase activity is non-linear. The addition of reduced glutathione protected against the inhibition of reductase activity by acrolein. Formation of these aldehydes and their subsequent inhibition of these enzymes may have important consequences in xenobiotic metabolism. PMID- 3103628 TI - Differential effects of manoalide on secreted and intracellular phospholipases. AB - Manoalide, a novel nonsteroidal sesterterpenoid, is a potent inhibitor of phospholipase A2 isolated from bee and cobra venoms. This report compares the inhibition by manoalide of phospholipase A2 in crude cytosol fractions from four mammalian tissues with that of four purified extracellular phospholipase A2's. Phospholipase A2 isolated from bee venom (Apis mellifera) was the most sensitive to inactivation by manoalide (IC50 approximately equal to 0.12 microM). Extracellular phospholipase A2 from rattlesnake and cobra venom was intermediate in sensitivity to manoalide (IC50 values of 0.7 and 1.9 microM respectively). Porcine pancreatic phospholipase A2 was relatively resistant to inactivation by manoalide (IC50 approximately equal to 30 microM). The phospholipase A2 assayed in crude cytosol fractions from four mammalian tissues exhibited IC50 values of 30 microM or greater. Cytosolic proteins as well as bovine serum albumin and poly L-lysine (Mr = 57,000) protected purified bee venom phospholipase A2 from inactivation by manoalide. In contrast, amino acids such as lysine and alanine failed to protect the purified enzyme from inactivation. Proteins and certain amino acids, such as lysine, formed a chromogenic product when incubated with manoalide. These data suggest that lysine is capable of reacting with manoalide, but only when it is present in macromolecules is it capable of protecting phospholipase A2 from inactivation by manoalide. Because cellular proteins protect PLA2 from inactivation by manoalide, high concentrations of manoalide must be applied topically to produce statistically significant inactivation of intracellular phospholipase A2. Finally, a chemical model is presented which explains the formation of a chromogenic product when manoalide is incubated with proteins and amino acids. PMID- 3103629 TI - Stimulatory and inhibitory regulation of myocardial adenylate cyclase by 5' guanylyl-imidodiphosphate. AB - Particulate and soluble rat myocardial adenylate cyclase enzymes were characterized with respect to their stimulatory and inhibitory regulation by Gpp(NH)p. Gpp(NH)p (60 microM) stimulated Mg2+- and Mn2+-dependent adenylate cyclase. High concentrations of Gpp(NH)p (600 microM) attenuated the maximal stimulatory response to Gpp(NH)p but only at low cation concentrations. The attenuating effects of 600 microM Gpp(NH)p resulted predominantly from the introduction of a prolonged lag in the kinetics of activation of adenylate cyclase. Steady-state rates of adenylate cyclase activities were similar with either 60 or 600 microM Gpp(NH)p. At any concentration of Gpp(NH)p, the lag was eliminated by Mg ions or isoproterenol. No antihysteretic property for free Mn ions was evident. Forskolin-sensitive particulate adenylate cyclase was not stimulated further by Gpp(NH)p. A 600 microM concentration of Gpp(NH)p inhibited particulate forskolin-sensitive adenylate cyclase at low Mg ion concentrations. In contrast, Gpp(NH)p at 60 microM consistently activated forskolin-sensitive adenylate cyclase after solubilization. The early transient inhibitory properties of 600 microM Gpp(NH)p which resulted in attenuation of adenylate cyclase by 600 microM Gpp(NH)p were diminished by detergent extraction, resulting in only a minor effect of 600 microM Gpp(NH)p to inhibit solubilized adenylate cyclase. These findings indicate that guanine nucleotides exert both stimulatory and inhibitory control upon the myocardial adenylate cyclase enzyme; that solubilization shifts the balance between the stimulatory and inhibitory properties of Gpp(NH)p to allow more dominant expression of the stimulatory response; and that Mg ions critically modify the nature of the myocardial adenylate cyclase response to Gpp(NH)p. PMID- 3103630 TI - Increase in renal cytochrome P-450 and NADPH cytochrome c reductase activity following drug inhibition of hepatic monooxygenase activity. PMID- 3103631 TI - Effect of hypolipidemic drugs on the metabolism of lauric acid and dimethylaminoazobenzene by rat liver microsomes. PMID- 3103632 TI - Defective in vitro gamma-interferon production in rheumatoid arthritis. PMID- 3103633 TI - Tenosynovitis in meningococcemia. PMID- 3103634 TI - HLA and the response to gold therapy in rheumatoid arthritis. PMID- 3103635 TI - High density lipoprotein, apoproteins A-I and A-II and postheparin plasma lipolytic enzymes after ileal bypass. AB - Apoproteins A-I and A-II, and the activities of lipoprotein lipase (LPL) and hepatic lipase (HL), were studied in 16 patients 3-12 years after ileal bypass operation and in 13 controls, all heterozygous for familial hypercholesterolemia, to investigate why the operated subjects had a higher HDL cholesterol level than the unoperated controls. HDL- and HDL2-cholesterol and apoprotein A-I were higher, HDL3-cholesterol was similar and apoprotein A-II tended to be lower in the operated than the control subjects. The activities of LPL and HL were similar in the 2 groups. HL was negatively correlated with HDL2-cholesterol, whereas LPL was not associated with any of the HDL components. The controls had gained in weight during the follow-up, but the HDL components were not correlated with relative body weight. It is concluded that in familial hypercholesterolemia ileal bypass results in higher HDL- and HDL2-cholesterol and apoprotein A-I level than conservative treatment and that postheparin plasma lipolytic enzymes do not explain the higher level of these HDL components in the operated subjects. PMID- 3103636 TI - Distribution and composition of HDL subclasses in students whose parents suffered prematurely from a myocardial infarction in comparison with controls. AB - The purpose of this study was to analyze the distribution and composition of the HDL subclasses in students whose parents suffered from a premature coronary heart disease (CHD), in comparison with a control group without any familial history of CHD. In the first part of this study, we observed significantly lower apo A-I concentrations in the cases than in the controls. Since there was a significant difference in smoking habits between cases and controls, and since we wanted to study the effect of a parental history of premature CHD on the composition of the HDL subclasses independently of smoking, the present study was conducted on the 17 pairs of non-smokers male cases and controls. In agreement with the results on total serum, we observed lower apo A-I concentrations in the HDL2b and HDL2a + 3a fractions in the cases compared to the controls. The apo A-II and cholesterol levels in these fractions were not significantly different between the 2 groups. The selective decrease of apo A-I in the HDL subclasses with the lowest density might be due to a decreased number of particles containing only apo A-I, with which a protective effect against atherosclerosis might be associated. PMID- 3103637 TI - Clinical, immunological, and virological aspects in Japanese hemophiliacs and AIDS patients. AB - To date, 16 cases of AIDS have been officially reported in Japan: 8 of them were hemophiliacs and the others were male homosexuals. We had two hemophiliacs with AIDS, and describe these cases in this paper. One was a 48-year-old man with hemophilia B and the other was a 62-year-old man with hemophilia A. Both had ARC symptoms before developing overt and fatal opportunistic infections, candidiasis and a combination of atypical mycobacteriosis and aspergillosis. Impairment of cellular immunity such as lowered T4/T8 ratio, depressed lymphocyte response to mitogen and NK activity, and negative PPD skin reaction was evident in both patients. Anti-LAV/HTLV-III antibodies were detected in their sera, and the retrovirus was demonstrated in the lymph nodes and other organs on the postmortem electron microscopic examination. The assay for anti-LAV/HTLV-III on 70 other hemophiliacs in our clinic revealed seropositivity up to 50%. The seropositive group showed a significantly lower T4/T8 ratio on an average than the seronegative group. The prevalence of seropositivity for antibodies to other viruses including HBV, EBV, CMV, PV, and HTLV-I was markedly higher in the hemophiliacs. In LAV/HTLV-III seropositive hemophiliacs, however, no distinct correlation was found between T4/T8 ratio and the presence of antibodies to other viruses. There is a retrospective study to show that LAV/HTLV-III seropositive hemophiliacs appeared as early as 1980 in Japan. For prevention of LAV/HTLV infection in hemophiliacs via blood products, heat-treated factor concentrates have recently become available. In a trial of the heat-treated products on 15 "virgin" hemophiliacs, no seroconversion has occurred thus far. PMID- 3103638 TI - Detection of antibody to LAV/HTLV-III in sera from hemophiliacs in China. AB - Using ELISA, Western blots and immunofluorescence techniques, we identified seropositivity for lymphadenopathy-associated virus/human lymphotropic virus-III (LAV/HTLV-III) in 4 of 18 hemophiliacs and 1 AIDS patient. The four seropositive patients had received factor VIII prepared by Armour Company. The hemophiliacs are all asymptomatic. Given this documentation of introduction of LAV/HTLV-III into China, a national surveillance program is underway. PMID- 3103639 TI - Prevalence and transmission of human immunodeficiency virus in Japan. AB - The routes of transmission of human immunodeficiency virus (HIV) can be divided into two categories, 1. sexual transmission (male-to-male, male-to-female and female-to-male) and 2. parenteral transmission by blood or blood products. Among 488 Japanese hemophiliacs, 165 (33.8%) were seropositive and were infected by the injection of factor VIII or factor IX manufactured from American sources. The rates of infection among hemophiliacs were 21.8% (19/87) and 36.8% (43/117), respectively for 1984 and 1985. Sera of 10,272 volunteer blood donors were all negative for anti-HIV. There have been 16 confirmed AIDS cases in Japan consisting of 8 male homosexuals and 8 hemophiliacs, so it can be concluded HIV infections have exclusively occurred among male homosexuals and hemophiliacs. But there are chances to transmit HIV by blood transfusion if the screening of whole blood units is not implemented in the near future. PMID- 3103640 TI - Prevalence of antibodies to AIDS-associated retrovirus in in- and out-patients in Japan. AB - Serum specimens from 252 recipients of factor VIII and/or factor IX (237 hemophiliacs and 15 nonhemophiliacs), 99 blood transfusion recipients, 269 chronic diseases, and 366 healthy subjects (included blood donors, hospital personnel and family members of hemophiliacs) were tested for reactivity to lymphadenopathy-associated virus/T-lymphotropic retrovirus type III (LAV/HTLV III) by ELISA test kit (Abbott), and the presence of the antibodies to LAV/HTLV III was confirmed by indirect immunofluorescence assay (IFA). Seropositivity rates were 38.4% (91 of 237) in hemophiliacs, 13.3% (2 of 15) in nonhemophiliac recipients of factor VIII and/or factor IX, and 8% (2 of 27) in male homosexuals. None of the other patients and healthy individuals had antibodies to LAV/HTLV III. In serological follow-up study on 40 seronegative and 10 seropositive hemophiliacs, 4 of the seronegative hemophiliacs converted to seropositive, and 7 of seropositive hemophiliacs had the antibody titers elevated by 2 to 4 fold within the period for 3.5 to 13 months after first blood samplings. Comparative analysis of the absolute numbers of T helper (T4) and T suppressor (T8) lymphocytes between the seropositive and seronegative hemophiliacs revealed that more than 50% of both seropositive and seronegative hemophiliacs had lower T4 lymphocyte numbers and higher T8 lymphocyte numbers than those of normal subjects. Particularly, over 80% of seropositive hemophiliacs had lower T4 lymphocyte numbers. Two Japanese AIDS cases (a hemophiliac B and a male homosexual) were found in the present study. Both died of pneumonia, and were confirmed officially as AIDS cases. PMID- 3103641 TI - [ELISA reaction for the diagnosis of South American trypanosomiasis. Limit absorbances for reacting and non-reacting sera]. PMID- 3103642 TI - [Chagas' disease in Chile. Rural and periurban Sectors. Positivity rates of the indirect hemagglutination reaction for the diagnosis of the parasitosis according to the number of persons examined per housing]. PMID- 3103643 TI - [Cerebral edema as a complication of a picture of diabetic ketoacidosis]. PMID- 3103644 TI - DNA repair in human cells: biochemistry of the hereditary diseases Fanconi's anaemia and Cockayne syndrome. Tenth Fritz-Lipmann lecture. PMID- 3103645 TI - The phycobiliprotein beta 16.2 of the allophycocyanin core from the cyanobacterium Mastigocladus laminosus. Characterization and complete amino-acid sequence. AB - The minor phycobiliprotein beta 16.2 was isolated from the APC-core of phycobilisomes from the cyanobacterium Mastigocladus laminosus. Its complete amino-acid sequence and some spectral characteristics are presented. beta 16.2 consists of 169 amino acids and its molecular mass is 19,390 Da. A phycocyanobilin chromophore is covalently bound to a cysteine at position 84 as in all other phycobiliproteins. The first 138 amino acids are highly homologous to the N-terminal part of beta AP (62.5%), whereas the C-terminal part has no homology. The absorption maximum is situated at 624 nm, the fluorescence emission maximum at 644 nm in phosphate buffer, pH 7.0. Both values are slightly redshifted compared with alpha AP and beta AP. PMID- 3103646 TI - Influence of EDTA and metal ions on a metalloproteinase from Pseudomonas fluorescens biotype I. AB - The inactivation of a metalloproteinase from Pseudomonas fluorescens Biotype I with EDTA was investigated at 22 degrees C and 37 degrees C. At 22 degrees C proteolytic activity decreases linearly with time and an inactive apoenzyme is obtained by dialysis. Proteolytic activity can be restored with several metal ions, Ca2+, Zn2+, Mg2+, Sr2+ and co2+ give the best results. Activity and substrate specificity are influenced by the metal-ions. Reactivation depends on the concentration of the metal-ions, optimum concentration is 1 mM for Ca2+ and 50 microM for Zn2+. The isoelectric point of the apoenzyme is around 8.0, this is about 0.3 pH-units lower than the isoelectric point of the native proteinase. At 37 degrees C inactivation follows first order kinetics and is irreversible because of autolysis as shown by a gel filtration-experiment. PMID- 3103647 TI - Isolation of follicular dendritic cells from human tonsils and adenoids. VI. Analysis of prostaglandin secretion. AB - Follicular dendritic cells (FDC) are able to fix high amounts of immune complexes by C3b or Fc receptors without endocytosis and for long periods of time. In order to determine the function of this retention, we analysed the secretion of prostaglandin E2 (PGE2) by FDC in vitro; indeed, it is well-known that immune complex fixation on cells may induce PGE2 production. FDC were isolated by enzymic digestion of lymph follicles dissected under the biomicroscope from human tonsils or adenoids. Isolated FDC appeared as spherical clusters where they enveloped lymphoid cells with their cytoplasmic extensions. Tests were performed in synthetic culture media or in media supplemented with foetal calf serum. PGE2 production in FDC suspensions was compared to that of lymphocyte or macrophage enriched populations prepared from the same human tonsils. In all experimental conditions, FDC and macrophage-enriched cell populations produced high levels of PGE2, inversely to lymphoid cell populations. This secretion was inhibited by indomethacin. At the ultrastructural level, we also showed that 3H-arachidonic acid was metabolized in cell membranes of all three cell types. The PGE2 produced in the culture media, according to our experimental conditions, do not influence cell proliferation, as assessed by 3H-thymidine incorporation tests on phytohaemagglutinin-stimulated lymphocytes. PMID- 3103648 TI - The peptidic self model: a reassessment of the role of the major histocompatibility complex molecules in the restriction of the T-cell response. AB - After having proposed, with the "peptidic self model", that class I or class II molecules of the major histocompatibility complex (MHC) expose peptides derived from self proteins on the surface of most somatic cells (as they do for foreign protein on the surface of macrophages, dendritic cells and B cells), we review here some of the recent evidence which suggests that the presentation of self or non-self peptides is strongly selected by the self-MHC molecules, in terms of amino acid sequence and possibly by three-dimensional conformation. On this basis, we further propose that T-cell receptors specifically recognize the exposed peptides, to the exclusion of the polymorphic parts of self-MHC molecules. Thus, the presentation of the antigen rather than its recognition by T cell would be "MHC-restricted". We show that such an inversion of perspective by which MHC molecules are seen as "peptide receptors" of degenerate specificity rather than "self markers" can provide, in the framework of the "peptidic self model", the basis for a consistent theory of self/non-self discrimination, alloreactivity and the ontogeny of the T-cell repertoire. PMID- 3103649 TI - Should fluid and nutritional support be withheld from terminally ill patients? Tube feeding in hospice settings. PMID- 3103650 TI - Pain control with sublingual morphine. The advantages for hospice care. PMID- 3103651 TI - [Epidemiologic study on the prevalence of Enterobacter, Serratia and Pseudomonas strains, producers of cefoxitin-inducible beta-lactamases]. AB - Resistance of Enterobacter, Serratia and pseudomonas strains to newer cephalosporins is often associated with stable derepression of synthesis of the chromosomal betalactamases. Similar resistance is developed by enzyme inducible strains in response to betalactamases inducers. This finding poses many clinical problems including emergence of resistance during therapy with the drugs. In this study we evaluated the MICs of several new betalactam compounds against 76 Enterobacter, Serratia and Pseudomonas strains before and after cefoxitin induction of betalactamases. The MICs against several Enterobacter strains (45%) after cefoxitin induction were elevated four fold or more. Serratia strains showed no significant variations of the MICs after cefoxitin induction. The MICs of piperacillin against many Pseudomonas strains (78%) after cefoxitin induction were elevated four fold or more. These data were confirmed using cefoxitin disk approximation test. Outbreaks of nosocominal infection with these multiresistant bacteria and spread of the strains throughout the hospital are already being seen. Control of these problems can only be achieved through the judicious and restricted use of these new antibiotics. PMID- 3103652 TI - [Bactericidal activity of beta-lactams and aminoglucosides: comparative evaluations]. AB - In this study we have evaluated the bactericidal activity kinetics of some cephalosporins, ureidopenicillins and aminoglycosides against 41 gram negative clinical isolates. Aminoglycosides, particularly gentamicin, showed the better bactericidal activity which appeared already at the second-third hour after the addition of the antibiotic. The bactericidal activity of cefotaxime, ceftazidime and cefotetan was remarkable but it appeared only at the sixth-eight hour. This difference was statistically significant. Carbenicillin and piperacillin showed a low bactericidal activity against Pseudomonas aeruginosa. We noted a wide variability of the antibiotic bactericidal activity against the isolates of the same bacterial species. Therefore we can argue that in serious infections the determination of the antibiotic and serum bactericidal activity is necessary. PMID- 3103653 TI - Ca2+ currents and acid secretion in the isolated parietal cell involved in response to gastrin, compound 48/80, and ethylenediamine tetraacetic acid. AB - In intact guinea pig parietal cells, gastrin or compound 48/80 caused an initial increase in cytosolic Ca2+ concentration and subsequent acid secretion, owing to release of intracellulary stored Ca2+ besides the Ca2+ entry from the extracellular space. However, the maximum gastrin-induced Ca2+ entry into the cell was delayed by 60 min, a time which coincided with sustained acid secretion (by gastrin) that was dependent on medium Ca2+. On the other hand, there are two ATP-dependent Ca2+-removal systems detected in either plasmalemma or smooth surfaced membrane besides that of mitochondria. The plasmalemmal Ca2+-removal system was dependent on calmodulin. Smooth surfaced membrane vesicles caused an ATP-dependent Ca2+ uptake that was almost similar to that taken by saponin permiabilized cell. In this system (permeable cell), myo-inositol 1,4,5 triphosphate (InsP3) caused the release of ATP-accumulated Ca2+ into the cytosol, suggesting an ATP-dependent and InsP3-sensitive Ca2+ pool(s) is in or near the smooth surfaced membranes. The ATP-dependent Ca2+ uptake by vesicles was markedly enhanced by the stimulation of cells with gastrin, compound 48/80, or EDTA. The increase of this Ca2+ uptake in stimulated cells by plasmalemmal vesicles exceeded that by smooth surfaced ones. The increase of the Ca2+ uptake by plasmalemmal vesicles was abolished by the cease of intracellular Ca2+ release without Ca2+ entry. In addition, gastrin or compound 48/80 evoked an early Ca2+ efflux across the plasma membrane owing to a pump that was independent of medium Ca2+ in intact cells. These results suggest that in the first acid secretion by gastrin or others, the Ca2+ released, which may be derived from an ATP-dependent and InsP3-sensitive Ca2+ pool, is mainly pumped out by the plasmalemmal Ca2+ removal system rather than the intracellular Ca2+-removal system; whereas the sustained acid secretion by gastrin required medium Ca2+ and in this phase, Ca2+ efflux across the plasma membrane became lower, suggesting that an ATP-dependent Ca2+ pool may be replenished by Ca2+ entering from the extracellular space. PMID- 3103654 TI - Isolation and characterization of a mitochondrial RNA polymerase from Drosophila melanogaster. AB - A DNA-dependent RNA polymerase was solubilized from sucrose gradient isolated, DNase-treated mitochondria of Drosophila melanogaster. The isolated mitochondria were not detectably contaminated with nuclear DNA as shown by CsCl gradient centrifugation and polylysine Kieselguhr chromatography. The detergent solubilized RNA polymerase was sensitive to rifampicin, resistant to alpha amanitin, had an apparent molecular mass of about 60 kilodaltons, and displayed a tendency to aggregate, both in crude extracts or when purified. The mitochondrial RNA polymerase could be distinguished from nuclear RNA polymerases on the basis of size, salt optima, rifampicin sensitivity, and alpha-amanitin resistance. PMID- 3103655 TI - [Comparison between 2 fits to compute platelet half-life measured with autologous platelets labeled by In-111-oxine]. PMID- 3103656 TI - [Clinical and biochemical approach to mitochondrial cytopathy--pyruvate dehydrogenase complex deficiency]. PMID- 3103657 TI - [Mitochondrial inheritance and disease]. PMID- 3103658 TI - G proteins: a family of signal transducers. PMID- 3103659 TI - Minimum volume of discard for valid blood sampling from indwelling arterial cannulae. AB - The volume of discard for valid blood sampling from indwelling femoral (leader cath) and radial (Venflon) arterial cannulae (with internal volume of cannula plus connecting tubing of approximately 2 ml) was investigated by analysing sequential 2-ml aliquots of 10-ml samples. The aliquots were analysed for pH, carbon dioxide tension, oxygen tension, standard bicarbonate, haemoglobin concentration, haemoglobin oxygen saturation and potassium concentration. Analysis of variance showed that, for these variables and these catheters, a valid blood sample was obtained after discarding 4 ml, but not after only 2 ml. The haemoglobin concentration, as measured by a Corning oximeter, provided good warning of inadequate discard. PMID- 3103660 TI - Estimation of arterial PCO2 during high frequency jet ventilation. Studies in the dog. AB - The arterial to end-tidal PCO2 difference (PaCO2-PE'CO2) was measured in five anaesthetized dogs during controlled ventilation at 0.25 Hz (15 b.p.m.) and during high frequency jet ventilation at 1, 3 and 5 Hz. Because of the slow response of the infra-red carbon dioxide analyser, satisfactory recordings of end tidal carbon dioxide could not be obtained at frequencies greater than 1 Hz. The interruption of high frequency jet ventilation by conventional ventilation resulted in approximately equal arterial and end-tidal PCO2 values during the first breath, and restoration of the normal arterial to end-tidal PCO2 difference by the third breath. It is concluded that, when high frequency jet ventilation at 1, 3 or 5 Hz is interrupted with normal tidal volumes at low frequencies, the arterial PCO2 can be estimated from recordings of the end-tidal PCO2. PMID- 3103661 TI - Extradural analgesia during labour using alfentanil. AB - Sixteen primiparous patients requesting pain relief during labour received a continuous infusion of alfentanil 30 micrograms kg-1 h-1 via an extradural catheter. Supplementary (extradural) bolus doses (30 micrograms kg-1) were administered when deemed necessary. Excellent pain relief was rapidly obtained early in labour in all patients. However, analgesia was inadequate in the latter part of stage I and during the second stage in five of the 16 patients- notwithstanding several additional doses of alfentanil, and bupivacaine had to be administered. No serious maternal side-effects, except nausea, were encountered. Although all neonatal Apgar scores were between 7 and 10, the Amiel-Tison test clearly indicated the existence of neonatal hypotonia. The continuous extradural administration of alfentanil proved to be unsatisfactory for pain relief in labour. PMID- 3103662 TI - Fresh gas flow requirements using the ADE anaesthetic system during late pregnancy. AB - Thirty-two pregnant patients at term undergoing elective Caesarean section were ventilated with a non-co-axial ADE anaesthetic system (E mode) supplied with fresh gas flows (FGF) of either 70 or 100 ml kg-1 min-1, on a random basis. Ventilation with an FGF of 70 ml kg-1 min-1 produced mean PaCO2 and PE' CO2 values of 6.48 +/- 1.15 kPa and 6.41 +/- 0.76 kPa, respectively. Patients were thus hypercapnic, which contrasts with the normocapnia achieved using an FGF of 100 ml kg-1 min-1 via the ADE system (E mode) (PaCO2 5.07 +/- 0.7 kPa; PE' CO2 4.83 +/- 0.46 kPa) (mean values +/- SD). The latter FGF is therefore recommended for the pregnant patient at term when using a Mapleson E system such as the Humphrey ADE apparatus. PMID- 3103663 TI - Anaesthesia for evacuation of retained products of conception. Comparison between alfentanil plus etomidate and fentanyl plus thiopentone. AB - Forty-four patients presenting for evacuation of retained products of conception were anaesthetized with either fentanyl and thiopentone, or alfentanil with etomidate, along with 70% nitrous oxide in oxygen. There was no difference between the two techniques in indices of immediate recovery (time to opening eyes and obeying a simple command), but the rate of return of higher mental functions (assessed by a coin counting test) was significantly better using the alfentanil etomidate technique. There was no statistically significant difference between the techniques for apnoea or abnormal movements during anaesthesia, but alfentanil with etomidate was associated with significantly more pain on injection and a higher frequency of postoperative vomiting (40%). PMID- 3103664 TI - Sinus arrest after alfentanil. PMID- 3103665 TI - The economic cost of alcohol-related health care in New Zealand. PMID- 3103666 TI - Effect of posture on glyceryl trinitrate plasma concentrations following transdermal application. PMID- 3103667 TI - Sensitivities of Pityrosporum sp. to selected commercial shampoos. AB - Sensitivity of 25 strains of Pityrosporum sp. to four commercial shampoos was tested using a gel diffusion method and determination of minimum inhibitory concentrations (MICs). All the shampoos when undiluted gave inhibition zones in the gel diffusion test with 13 of the 15 strains tested. Two strains were resistant to 'Polytar'. 'Polytar' was fungistatic, 'Selsun' 'Cetavlon P.C.' and 'Genisol' were fungicidal. MIC results showed the yeast to be most sensitive to 'Cetavlon' and 'Selsun'. PMID- 3103668 TI - Human epidermal cells express Leu-IIb antigen. PMID- 3103669 TI - Simultaneously increased expression of the c-myc and mu chain genes in the acute blastic transformation of a chronic lymphocytic leukaemia. AB - A B-cell chronic lymphocytic leukaemia terminated, 5 years from the onset, with a blast crisis. Karyotype analysis showed that the terminal lymphoblastic population evolved from the original B lymphocytic clone. The levels of expression of several oncogenes, as well as the mu chain gene, were assayed by Northern blot hybridization analysis of RNA extracted from the lymphoid populations before and after the 'acute transformation'. A seven- to eight-fold increase in the expression of c-myc and mu chain genes was observed in the blast population. c-myb, c-fes, c-Haras were not expressed either before or after the blastic transformation. PMID- 3103670 TI - Increased concentration of the fast-acting plasminogen activator inhibitor in plasma associated with familial venous thrombosis. AB - We have earlier demonstrated that in a family with a tendency to recurrent venous thrombosis the release of tissue plasminogen activator (t-PA) activity in blood after stimulation was abnormally low. This observation could be related either to an impaired release of t-PA into the blood stream or to a masking of the released t-PA by a high concentration of PA inhibitor(s). In order to distinguish between these two possibilities the family was reinvestigated using various newer techniques, including an ELISA for t-PA, an assay for quantitation of the fast acting PA inhibitor and SDS polyacrylamide gel electrophoresis followed by fibrin enzymography. Hereby the family members were demonstrated to have a high concentration in plasma of the PA inhibitor. After stimulation the release of t PA into the blood was normal, the t-PA activity, however, was immediately inactivated by complex formation with the fast-acting PA inhibitor. PMID- 3103671 TI - Serum gonadotrophin and sex steroid hormone levels during mid-follicular and mid luteal phases in hyperprolactinaemic women with regular menstrual cycles. AB - Hyperprolactinaemia was found in 15 of 135 infertile patients with regular menstrual cycles, biphasic basal body temperature record and no galactorrhoea. In those 15 women, mean serum prolactin levels during the mid-follicular and mid luteal phases of the menstrual cycle were 29.8 (SEM 1.8) ng/ml and 29.5 (SEM 1.3) ng/ml, respectively. Although serum FSH and LH levels were similar in normal and hyperprolactinaemic women, serum oestradiol level during the mid-follicular phase was subnormal in hyperprolactinaemic women (P less than 0.05). In contrast, serum oestradiol and progesterone levels during the mid-luteal phase and luteal phase length were similar in normoprolactinaemic and hyperprolactinaemic groups. The results suggest that hyperprolactinaemia is associated with defects of follicle development as measured by oestradiol production during the mid-follicular phase, but not with corpus luteum function as measured by progesterone production during the mid-luteal phase, and luteal phase length. PMID- 3103672 TI - Host, microbial, and pharmacological factors affecting the outcome of suppurative keratitis. AB - A review of 87 cases of microbial keratitis in South Australia was made to determine the factors which influence the outcome of the disease. The preceding pathology and the extent of ulceration at presentation were found to be significant, while the presence of hypopyon was less important. Infection with Pseudomonas aeruginosa was most likely to result in a poor outcome. Most patients had a history of traumatic injury, herpes simplex keratitis, or a corneal graft. The choice of gentamicin and a cephalosporin as appropriate initial therapy in Australia was supported. The results are discussed with reference to current research objectives. PMID- 3103673 TI - Ophthalmic manifestations of neurofibromatosis. AB - The eyes of 64 patients known to have neurofibromatosis were examined. Lisch nodules were the commonest manifestation of the disease and were present in 95% of all patients (100% of those aged 16 years or older). PMID- 3103674 TI - Molecular basis of the oxygen exchange from CO2 catalyzed by carbonic anhydrase III from bovine skeletal muscle. AB - The exchange of 18O from CO2 to H2O in aqueous solution is caused by the hydration-dehydration cycle and is catalyzed by the carbonic anhydrases. In our previous studies of 18O exchange at chemical equilibrium catalyzed by isozymes I and II of carbonic anhydrase, we observed simple first-order depletion of 18O from CO2 with the 18O distribution among the species C18O18O, C16O18O, and C16O16O described by the binomial expansion (i.e., a random distribution of 18O). Using membrane-inlet mass spectrometry, we have measured 18O exchange between CO2 and H2O catalyzed by native zinc-containing and cobalt(II)-substituted carbonic anhydrase III from bovine skeletal muscle near pH 7.5. The distributions of 18O in CO2 deviate from the binomial expansion and are accompanied by biphasic 18O exchange patterns; moreover, we observed regions in which 18O loss from CO2 was faster than 18O loss from HCO3-. These data are interpreted in terms of a model that includes 18O loss from an enzyme-substrate or intermediate complex. We conclude that more than one 18O can be lost from CO2 per encounter with the active site of isozyme III, a process that requires scrambling of oxygens in a bicarbonate-enzyme complex and cycling between intermediate complexes. This suggests that the rate of dissociation of H2(18)O (or 18OH-) from isozyme III is comparable to or faster than substrate and product dissociation. PMID- 3103675 TI - Intramembranal events in the biosynthesis of peptidoglycan in Gaffkya homari. AB - In order to monitor the intermediates involved in nascent peptidoglycan (PG) assembly in Gaffkya homari, a pulse/chase assay utilizing UDP-MurNAc-Ala-DGlu Lys(N epsilon-Dns)-DAla-DAla [Dns (dansyl) = 5-(dimethylamino)naphthalene-1 sulfonyl] was devised. The perturbation introduced by the dansyl group provided a means for separating the synthesis of nascent PG into discrete stages. Together with paramagnetic quenching of the fluorophore by n-doxylstearic acids (n = 5, 7, 12, 16; doxyl = N-oxy-4',4'-dimethyloxazolidine), this assay allows one to observe the synthesis of undecaprenyl diphosphate-MurNAc-[N epsilon Dns)pentapeptide)-GlcNAc and its utilization for the formation of dansyl-labeled PG by fluorescence emission and by change in specific positional quenching. The utilization of the dansylated lipid disaccharide-pentapeptide occurs without a lag, whereas the formation of the chromatographically immobile dansylated PG occurs with a lag of 4-6 min. Membrane-associated undecaprenyl diphosphate-MurNAc (N epsilon-Dns)-pentapeptide was quenched primarily by 7-doxylstearate. In contrast, the fluorophore of the undecaprenyl diphosphate-MurNAc-[N epsilon Dns)pentapeptide)-GlcNAc was quenched primarily by 5-doxyl- and 16 doxylstearates. In the chase phase of the assay, quenching by 16-doxylstearate decreased at a faster rate than that by 5-doxylstearate during the formation of dansyl-labeled PG. PMID- 3103676 TI - Association of protein kinase C with phospholipid vesicles. AB - The Ca2+- and phospholipid-dependent protein kinase, protein kinase C (PKC), was purified from bovine brain by a modified procedure that provided sufficient quantities of stable protein for analysis of physical properties of protein membrane binding. The binding of PKC to phospholipid vesicles of various compositions was investigated by light-scattering and fluorescence energy transfer measurements. The binding properties for membranes of low phosphatidylserine (PS) content were consistent with a peripheral membrane association; PKC showed Ca2+ -dependent binding to phospholipid vesicles containing phosphatidylserine, phosphatidylinositol, or phosphatidylglycerol. Membranes containing 0-20% PS (the remainder of the phospholipid was phosphatidylcholine) bound less protein than membranes containing greater than 20% PS; the factor limiting protein binding to membranes containing low PS appeared to be the availability of acidic phospholipids. Increasing the PS content above 20% did not increase the amount of membrane-bound protein at saturation, and the limiting factor was probably steric packing of protein on the membrane surface. The membranes bound about 1 g of protein/g of phospholipid at steric saturation. Binding was of relatively high affinity (Kd less than 5 nM), and the association rate was rapid on the time scale of the experiments. Addition of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to phospholipid-bound PKC caused dissociation of the complex, and the properties of this dissociation indicated an equilibrium binding of protein to membrane. However, only partial dissociation of PKC was achieved when the PS content of the vesicles exceeded 20%. A number of comparisons revealed that binding of protein to the membrane, even in the presence of phorbol esters, was insufficient for development of enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103677 TI - Paramagnetic carbon-13 NMR relaxation studies on the kinetics and mechanism of the HCO3-/CO2 exchange catalyzed by manganese(II) human carbonic anhydrase I. AB - A detailed analysis of the stability and activity of Mn(II) human carbonic anhydrase I and the kinetics and mechanism of its catalysis of the HCO3-/CO2 exchange have been performed at pH 8.5. The analysis was based on the paramagnetic relaxation rates R1p and R2p of the 13C atom of HCO3- in the Mn2+/apoenzyme/HCO3-/CO2 system and the HCO3(-)----CO2 interconversion rate obtained by the magnetization-transfer technique. The R1p and R2p rates were measured as functions of the temperature, magnetic field strength, and substrate and apoenzyme concentrations and were interpreted on the basis of the Solomon Bloembergen-Morgan theories and general equations for the ligand exchange [Led, J. J., & Grant, D. M. (1977) J. Am. Chem. Soc. 99, 5845-5858]. From the analysis of the data, a formation constant for the Mn(II) enzyme of log KMAM = 5.8 +/- 0.4 was obtained while the activity of the Mn(II) enzyme, measured as the HCO3-/CO2 interconversion rate at [HCO3-] = 0.100 M and pH 8.5, was found to be about 4% of that of the native Zn(II) enzyme. However, an effective dissociation constant KeffHCO3- less than or approximately 12 mM and a maximal exchange rate constant kcatexch approximately equal to 400 s-1, also derived by the analysis, result in an apparent second-order rate constant kcatexch/KeffHCO3- only a factor of 4 smaller than the corresponding rate constant for the native Zn(II) isoenzyme I. Most conspicuously, the resulting distance of only 2.71 +/- 0.03 A between the Mn2+ ion of the enzyme and the 13C atom of HCO3- in the enzyme-bicarbonate complex indicates that the bicarbonate is bound to the metal ion by two of its oxygen atoms in the central catalytic step, thereby supporting the modified Zn(II)-OH mechanism [Lindskog, S., Engberg, P., Forsman, C., Ibrahim, S. A., Jonsson, B.-H., Simonsson, I., & Tibell, L. (1984) Ann. N.Y. Acad. Sci. 429, 61 75 (and references cited therein)]. In contrast, this binding mode differs from the structure of the complexes suggested in the rapid-equilibrium kinetic model [Pocker, Y., & Deits, T. L. (1983) J. Am. Chem. Soc. 105, 980-986; Pocker, Y., & Deits, T. L. (1984) Ann. N.Y. Acad. Sci. 429, 76-83]. PMID- 3103678 TI - Purification of sarcotoxin II, antibacterial proteins of Sarcophaga peregrina (flesh fly) larvae. AB - Three antibacterial proteins with almost identical primary structures termed sarcotoxin IIA, IIB, and IIC were purified to homogeneity from the hemolymph of third instar larvae of Sarcophaga peregrina. The molecular masses of these proteins were about 24,000. These proteins were found to have common antigenicity, and antibody against sarcotoxin IIA cross-reacted with sarcotoxin IIB and IIC. Radioimmunoassay using this antibody showed that these proteins are induced in the hemolymph in response to injury of the larval body wall. PMID- 3103679 TI - Kinetics of allophycocyanin's trimer-monomer equilibrium. AB - Kinetic studies of the dissociation of allophycocyanin trimers to monomers have been performed by using stopped-flow techniques. The dissociation was monitored by two techniques: by light scattering to observe the molecular weight changes directly and by 650-nm absorbance to observe the linkage of quaternary structure to spectra. The light-scattering experiments showed a simple exponential decay of trimers to monomers with a dissociation constant of 0.23 s-1. The absorption changes were complex, with two processes occurring. The faster absorption change appeared to be almost simultaneous with the molecular weight change (about 0.27 s 1) and was perhaps totally coordinated with it. The slower absorption change (0.071 s-1) was possibly a result of a conformational change in the chromophore arising during the conversion from newly dissociated monomers to equilibrium monomers. PMID- 3103680 TI - Functional role of proteolytic cleavage at arginine-275 of human tissue plasminogen activator as assessed by site-directed mutagenesis. AB - Activation of the zymogen form of a serine protease is associated with a conformational change that follows proteolysis at a specific site. Tissue-type plasminogen activator (t-PA) is homologous to mammalian serine proteases and contains an apparent activation cleavage site at arginine-275. To clarify the functional consequences of cleavage at arginine-275 of t-PA, site-specific mutagenesis was performed to convert arginine-275 to a glutamic acid. The mutant enzyme (designated Arg-275----Glu t-PA) could be converted to the two-chain form by Staphylococcus aureus V8 protease but not by plasmin. The one-chain form was 8 times less active against the tripeptide substrate H-D-isoleucyl-L-prolyl-L arginine-p-nitroanilide (S-2288), and the ability of the enzyme to activate plasminogen in the absence of fibrinogen was reduced 20-50 times compared to the two-chain form. In contrast, one-chain Arg-275----Glu t-PA has equal activity to the two-chain form when assayed in the presence of physiological levels of fibrinogen and plasminogen. Fibrin bound significantly more of the one-chain form of t-PA than the two-chain form for both the wild-type and mutated enzymes. One- and two-chain forms of the wild-type and mutated plasminogen activators slowly formed complexes with plasma protease inhibitors, although the one-chain forms showed decreased complex formation with alpha 2-macroglobulin. The one-chain form of t-PA therefore is fully functional under physiologic conditions and has an increased fibrin binding compared to the two-chain form. PMID- 3103681 TI - Separation of the protective enzyme bleomycin hydrolase from rabbit pulmonary aminopeptidases. AB - Bleomycin (BLM) hydrolase inactivates the BLM class of antitumor antibiotics and protects against BLM-induced pulmonary fibrosis. This enzyme is poorly characterized but believed to be an aminopeptidase B. In the present report, both BLM hydrolase and aminopeptidase B from rabbit pulmonary cytosol were retained by arginyl-Sepharose and BLM-Sepharose affinity columns, further suggesting that these two enzymes are similar. When, however, BLM hydrolase was purified over 1800-fold by using our newly developed high-speed liquid chromatography assay for BLM hydrolase coupled with fast protein liquid chromatography, we found that this partially purified BLM hydrolase preparation lacked aminopeptidase B activity. Furthermore, BLM hydrolase was completely separated, by using anion-exchange Mono Q chromatography, from all the aminopeptidases identified in rabbit pulmonary cytosol: one aminopeptidase B, two aminopeptidases N, and one aminopeptidase with both aminopeptidase B and aminopeptidase N activities. Pulmonary BLM hydrolase also had a higher molecular weight than pulmonary aminopeptidase B. In contrast to aminopeptidase B, BLM hydrolase was not activated by NaCl and was much less stable at 4 degrees C. In addition, bestatin was a potent inhibitor of aminopeptidase B but had little effect on BLM hydrolase, while leupeptin was a potent inhibitor of BLM hydrolase but was less effective against aminopeptidase B. Thus, pulmonary BLM hydrolase and aminopeptidase B have affinity for each other's substrate, but they are clearly distinct enzymes on the basis of charge characteristics, molecular weight, stability, and sensitivity to inhibitors and activators. PMID- 3103682 TI - Complete amino acid sequences of the heavy and light chain variable regions from two A/J mouse antigen nonbinding monoclonal antibodies bearing the predominant p azophenyl arsonate idiotype. AB - The immune response to p-azophenyl arsonate (Ars) in A/J mice is dominated by a cross-reactive idiotype (CRI or IdCR). IdCR+ hybridoma proteins 1F6 and 3D10 produced in a single mouse by immunization with a monoclonal anti-IdCR antibody did not bind Ars [Wysocki, L., & Sato, V. (1981) Eur. J. Immunol. 11, 832-839]. The preservation of idiotype coupled with lack of antigen binding in the same molecules provoked an examination of their primary structures in order to localize sites involved in binding to antigen and to anti-idiotypes. The VH sequence of antibody 3D10 was determined by Edman degradation of intact chains and fragments generated by CNBr, hydroxylamine, and o-iodosobenzoic acid cleavage, by trypsin and V8 protease digestion, and by sequence analysis of mRNA. The 1F6 VH sequence was reported previously [Smith, J. A., & Margolies, M. N. (1984) Biochemistry 23, 4726-4732]. The VL sequences of 1F6 and 3D10 were determined by Edman degradation of intact chains and peptides generated by cleavage with o-iodosobenzoic acid and digestion with trypsin and chymotrypsin. Both 1F6 and 3D10 are encoded by the same VH, VK, D, and JK gene segments as are IdCR+ Ars-binding antibodies. However, 1F6 and 3D10 employ the JH4 gene segment rather than JH2. Antibodies 1F6 and 3D10 share several somatic mutations, suggesting a common clonal origin, but manifest individual mutations as well. By comparison with Ars-binding IdCR+ molecules, the substitutions in 1F6 and 3D10 likely responsible for the lack of Ars binding are localized to the heavy chain D JH junction and/or to a substitution in light chain CDR 3. PMID- 3103683 TI - Cross talk between stimulatory and inhibitory guanosine 5'-triphosphate binding proteins: role in activation and desensitization of the adenylate cyclase response to vasopressin. AB - The inhibitory GTP-binding protein (Gi) is known to mediate the effects of a number of hormones that act through specific receptors to inhibit adenylate cyclase. In this study we examined the mechanism whereby Gi modulates the response of adenylate cyclase to a stimulatory hormone and its role in desensitization. In membranes prepared from the cultured renal epithelial cell line LLCPK1, adenylate cyclase activity was stimulated 16-fold by 1-2 microM lysine vasopressin. Addition of GTP (1-100 microM) resulted in stimulation of basal activity but inhibition of hormone-stimulated activity (approximately 40% inhibition at 100 microM GTP). This contrasts with the usual effect of GTP to support or augment activation by stimulatory receptors. The inhibitory effect was abolished by pertussis toxin, which had little effect on basal activity in the absence or presence of added GTP or on vasopressin-stimulated activity in the absence of added GTP. GTP-mediated inhibition was vasopressin concentration dependent. At concentrations of vasopressin below the K1/2 for enzyme activation (approximately 0.6 nM), GTP was stimulatory, and at higher concentrations, GTP was inhibitory. The inhibitory effect of GTP was also observed for a V2-receptor agonist and was not abolished by a V1-receptor antagonist, indicating that a distinct V1 receptor did not mediate inhibition of adenylate cyclase. Using the known subunit structure of adenylate cyclase, we developed the minimal mechanism that would incorporate a modulatory role for Gi in determining net activation of adenylate cyclase by a stimulatory hormone. The predicted enzyme activities for basal and maximal hormone stimulation in the presence and absence of GTP were generated, and model parameters were chosen to match the experimental observations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103684 TI - Hydrogen peroxide as an alternate substrate for the oxygen-evolving complex. AB - Photosystem II reaction centers evolve O2 in the dark when H2O2 is added as a substrate. Although some of this activity can be attributed to catalase, as much as 75% of the activity was not affected by the addition of 1 mM KCN. Several lines of evidence demonstrate that this KCN-insensitive O2 evolution from H2O2 in the dark is catalyzed by the cycling of S states in the oxygen-evolving complex including: inactivation of H2O2-mediated O2 evolution by Ca/EDTA washing; susceptibility of the activity to inhibition by amines like ammonia and Tris; inhibition by CCCP which is known to accelerate the rate of deactivation of the S2 state and; a direct dependence of the rate of O2 evolution on the presence of calcium and chloride. PMID- 3103685 TI - Further studies on amino acid transport in murine P388 leukemia cells in vitro. Presence of system y+. AB - The transport of glycine and L-lysine into murine P388 leukemia cells has been examined. Glycine transport appears to be shared by both systems A and ASC in P388 cells. Glycine transport is Na+-dependent and is effectively blocked by alpha-(methylamino)isobutyric acid, threonine and alanine but only a marginal reduction in transport is seen with 100-fold excess cold 2 aminobicyclo[2,2,1]heptane-2-carboxylic acid. System gly is not expressed in P388 cells. Lysine is largely transported by a Na+-independent, pH-insensitive system with a Km of 0.079 mM. Lysine transport is relatively unaffected by the addition of 100-fold excess cold alpha-(methylamino)isobutyric acid, 2 aminobicyclo[2,2,1]heptane-2-carboxylic acid and the anionic amino acids, L glutamate and L-aspartate. A partial inhibition of lysine transport was observed with L-threonine and L-leucine while L-arginine and L-histidine radically decreased lysine transport. Lysine appears to be transported by a system similar to the system y+ seen in cultured human fibroblasts, Ehrlich ascites cells, and hepatoma cell lines. PMID- 3103686 TI - Tissue-type plasminogen activator and urokinase: differences in the reaction pattern with the active-site titrant 4-methylumbelliferyl-p-guanidinobenzoate hydrochloride. AB - The applicability of 4-methylumbelliferyl-p-guanidinobenzoate hydrochloride (MUGB) as active-site titrant for tissue-type plasminogen activator (t-PA) was studied in comparison to urokinase. Although t-PA was capable of cleaving MUGB, active-site titration of t-PA (one-chain form as well as two-chain form) with MUGB was not possible, whereas MUGB titration of urokinase could be performed. We therefore studied the kinetics of the interaction of these two plasminogen activators with MUGB. The equilibrium dissociation constant, KS, for the interaction between MUGB and urokinase was 2.9 X 10(-6) M, and for the interaction with t-PA 3.13 X 10(-5) M. However, one main requirement for active site titration, namely a stable acyl enzyme intermediate (ES'), was only fulfilled for MUGB urokinase but not for MUGB t-PA. Whereas for the reaction of MUGB and urokinase the first-order acylation rate constant k2 was found to be about 10(6)-times higher than the first-order deacylation rate constant k3 (k2 = 3.76 X 10(-1) s-1, k3 = 3.7 X 10(-7) s-1), the k2/k3 ratio for the reaction of MUGB and t-PA (one- and two-chain form) was 0.77 to 3.85. Therefore, urokinase and t-PA differ in their reaction with this fluorogenic substrate and MUGB cannot be used for active-site titration of tPA. PMID- 3103687 TI - Kinetics of activation of L-lactate dehydrogenase from Streptococcus faecalis by fructose 1,6-bisphosphate and by metal ions. AB - The lactate dehydrogenase from Streptococcus faecalis is activated either by fructose 1,6-bisphosphate or by divalent cations such as Mn2+ or Co2+. With both types of activator, a lag is observed before attainment of the steady state rate of pyruvate reduction if the activator is added to the enzyme at the same time as the substrates. This lag can be largely abolished by preincubation of enzyme with activator before mixing with substrates. For fructose 1,6-bisphosphate (Fru(1,6)P2) as the activator, the rate constant for the lag phase showed a linear dependence on activator concentration but was independent of enzyme concentration. This suggests that binding of fructose 1,6-bisphosphate induces a conformational change in the enzyme which leads to increased activity, without association of enzyme subunits or dimers. With Co2+ as activator, the rate constant for the lag phase showed a hyperbolic dependence on Co2+ concentration and was also dependent on enzyme concentration. This suggests that activation by Co2+, in contrast to that by Fru(1,6)P2, involves association of enzyme dimers, followed by ligand binding. PMID- 3103688 TI - Regulation of apolipoprotein A-I synthesis in lymph-drained rats. AB - The effect of lymph diversion on plasma apolipoprotein A-I levels was studied. In lymph fistula rats apolipoprotein A-I levels in plasma stayed constant in spite of a loss of an equivalent of one-half plasma pool of apolipoprotein A-I per day through the lymph fistula. This indicates that synthesis of apolipoprotein A-I increases or that catabolism of apolipoprotein A-I decreases in a compensatory manner as intestinal apolipoprotein A-I is diverted. By using incorporation of [3H]leucine into newly synthesized apolipoprotein A-I it was shown that 2.6-times as much [3H]leucine was incorporated into apolipoprotein A-I in thoracic duct drained animals compared to controls. In experiments in which 125I-labeled HDL was injected intravenously into rats, it was shown that catabolism of HDL and apolipoprotein A-I was not decreased in lymph-drained rats. These data thus suggest that an increased synthesis of apolipoprotein A-I occurs when the intestinal contribution of apolipoprotein A-I diminishes. This is probably due to an increase in liver protein synthesis. PMID- 3103689 TI - Effects of levonorgestrel on enzymes responsible for synthesis of triacylglycerols in rat liver. AB - The effects of levonorgestrel treatment (4 micrograms/day per kg body weight 0.75 for 18 days) on rate-limiting enzymes of hepatic triacylglycerol synthesis, namely glycerol-3-phosphate acyltransferase and phosphatidic acid phosphatase were investigated in microsomal, mitochondrial and cytosolic fractions of rat liver. Levonorgestrel treatment resulted in a significant reduction (26%) of hepatic microsomal glycerol-3-phosphate acyltransferase specific activity. Hepatic mitochondrial glycerol-3-phosphate acyltransferase specific activity was unchanged. Levonorgestrel treatment also significantly reduced (by 20%) the specific activity of hepatic microsomal magnesium-independent phosphatidic acid phosphatase. However, magnesium-dependent phosphatic acid phosphatase specific activities in microsomal and cytosolic fractions were unaffected. Cytosolic magnesium-independent phosphatidic acid phosphatase activity was also unchanged. These studies are consistent with the view that levonorgestrel lowers serum triacylglycerol levels, at least in part, by inhibition of the glycerol-3 phosphate acyltransferase (EC 2.3.1.15) step in hepatic triacylglycerol synthesis. PMID- 3103690 TI - Aromatic boronic acids as probes of the catalytic site of human plasma lecithin cholesterol acyltransferase. AB - We have recently proposed a catalytic mechanism for human plasma lecithin cholesterol acyltransferase (EC 2.3.1.43) (J. Biol. Chem. (1986) 261, 7032-7043), implicating single serine and histidine residues in phosphatidylcholine cleavage and two cysteine residues in cholesterol esterification. We now confirm the involvement of serine and histidine in catalysing the phospholipase A2 action of lecithin-cholesterol acyltransferase by demonstrating the inhibition of this activity by phenylboronic acid (Ki = 1.23 mM) and m-aminophenylboronic acid (Ki = 2.32 mM), inhibitors of known serine/histidine hydrolases. The specificity of the interaction of aromatic boronic acids with catalytic serine and histidine residues and the putative formation of a tetrahedral adduct between boron and the lecithin-cholesterol acyltransferase serine hydroxyl group which is similar to the transition-state intermediate formed between phosphatidylcholine and the catalytic serine residue was suggested by: substrate protection against inhibition by phenylboronic acids; a much reduced incorporation of phenylmethane[35S]sulphonyl fluoride into the enzyme in the presence of phenylboronic acid; the lack of interaction of histidine- or serine-modified enzyme with immobilized phenylboronic acid in the presence of glycerol (Ve/Vo = 2.7 and 2.3 respectively) when compared to the native enzyme (Ve/Vo = 5.25). Fatty acyl-lecithin-cholesterol acyltransferase, produced by incubation of the enzyme with a lecithin-apolipoprotein A-I proteoliposome substrate, was not retarded upon the sorbent column (Ve/Vo = 1.5). Modification of the enzyme's two free cysteine residues with 5,5'-dithiobis(2-nitrobenzoic acid) or potassium ferricyanide reduced (Ve/Vo = 3.5) but did not abolish retardation on the sorbent column, indicating that these modifications resulted in steric hinderance of the interaction of the boron atom with the lecithin-cholesterol acyltransferase serine hydroxyl group. These data suggest that the serine and histidine residues are proximal within the enzyme catalytic site and that both cysteine thiol groups are close to the serine hydroxyl group. The presence of significant amino-acid sequence homologies between lecithin-cholesterol acyltransferase, triacylglycerol lipases and the transacylases of fatty acid synthase is also reported. PMID- 3103691 TI - Macrophage eicosanoid formation is stimulated by platelet arachidonic acid and prostaglandin endoperoxide transfer. AB - The present study was designed to determine whether platelets transfer arachidonic acid or prostaglandin endoperoxide intermediates to macrophages which may be further metabolized into cyclooxygenase products. Adherent peritoneal macrophages were prepared from rats fed either a control diet or an essential fatty acid-deficient diet, and incubated with a suspension of washed rat platelets. Macrophage cyclooxygenase metabolism was inhibited by aspirin. In the presence of a thromboxane synthetase inhibitor, 7-(1-imidazolyl)heptanoic acid, immunoreactive 6-ketoprostaglandin F1 alpha formation was significantly increased 3-fold. Since this increase was greater (P less than 0.01) than that seen with either 7-(1-imidazolyl)heptanoic acid-treated platelets or aspirin-treated macrophages alone, these results indicate that shunting of endoperoxide from platelets to macrophages may have occurred. In further experiments, macrophages from essential fatty acid-deficient rats were substituted for normal macrophages. Essential fatty acid-deficient macrophages, depleted of arachidonic acid, produced only 2% of the amount of eicosanoids compared to macrophages from control rats. When platelets were exposed to aspirin, stimulated with thrombin, and added to essential fatty acid-deficient macrophages, significantly more immunoreactive 6-ketoprostaglandin F1 alpha was formed than in the absence of platelets. This increased macrophage immunoreactive 6-ketoprostaglandin F1 alpha synthesis, therefore, must have occurred from platelet-derived arachidonic acid. These data indicate that in vitro, in the presence of an inhibition of thromboxane synthetase, prostaglandin endoperoxides, as well as arachidonic acid, may be transferred between these two cell types. PMID- 3103692 TI - The existence of apotyrosinase in the cytosol of Harding-Passey mouse melanoma melanocytes and characteristics of enzyme reconstitution by Cu(II). AB - This paper reports the effect of Cu(II) supplementation on the tyrosinase isozymes from Harding-Passey mouse melanoma. The dopa-oxidase activity of the microsomal and soluble isozymes is increased by incubation with Cu(II), whereas the activity of the unique 'in vivo' melanin-forming isozyme, bound to melanosomes, is not. Other divalent cations are ineffective in increasing the dopa-oxidase activity of tyrosinases. These results indicate the existence of a mixture of tyrosinase and apotyrosinase in the cytosol of melanocytes before reaching the melanosome. The paucity of Cu(II) in the cytosol could be one of the mechanisms of regulation contributing to avoid the formation of melanin outside the melanosome. Some kinetic characteristics of the enzymatic reconstitution of soluble and microsomal isozymes by Cu(II) are also studied, and the results suggest that the glycosylation of apotyrosinase during its maturation yields a conformational change favouring the binding of Cu(II) at the enzyme active site, by lowering the activation energy of the reconstitution reaction. PMID- 3103693 TI - Heterogeneity of reducing terminals of urinary chondroitin sulfates. AB - Human urinary chondroitin sulfates were isolated by precipitation with cetylpyridinium chloride of the non-dialyzable fraction of pooled urine, followed by ethanol fractionation and successive enzymic digestions with neuraminidase and mucopolysaccharides. Further purification was achieved by Dowex-1 chromatography with stepwise elution by increasing the concentration of NaCl at intervals of 0.25 M from 0.75 M to 1.5 M. The chondroitin sulfates thus obtained were characterized by the analysis and quantification on of carbohydrate, amino acid and sulfate, and by electrophoresis on cellulose acetate membrane. Then reducing terminals were identified by gas liquid chromatographic analyses of the acetyl and butaneboronate derivatives of hydrolysates, after reduction of the reducing terminals with sodium borohydride. About 22.8% of the urinary chondroitin sulfate in the 1.5 M fraction was peptide-bound, and the remainder was peptide-free, with xylose (29.8%), galactose (23.6%) and glucuronic acid (18.7%) at the reducing terminal. The amount of peptide-free chondroitin sulfate with xylose and galactose at its reducing terminals in the 0.75 M-, 1.0 M-, 1.25 M- and 1.5 M fractions increased in the order described in parallel with the increase of sulfation and the decrease of peptide content. It was thus suggested that the endo-types of beta-xylosidase, beta-galactosidase and beta-glucuronidase acted on the carbohydrate-peptide linkage region of proteo-chondroitin sulfate in the tissues and produced various types of urinary chondroitin sulfate with heterogeneity at reducing terminals. PMID- 3103694 TI - The origin of the sulfur atom of thiamin. AB - The incorporation of the sulfur atom of 35S-labeled amino acids into thiamin in Escherichia coli and Saccharomyces cerevisiae was studied. The specific radioactivity of the S atoms was incorporated at similar levels into thiamin and cysteine residues in cell proteins. However, the specific radioactivity of the S atoms from [35S]methionine was not incorporated into thiamin but into methionine residues in cell proteins. Thus, the origin of the S atom of thiamin was established as being the S atom of cysteine. No activity from [U-14C]cysteine was recovered in thiamin, proving that the carbon skeleton of this amino acid was not utilized in synthesizing the thiazole moiety of thiamin. PMID- 3103695 TI - Solubility properties of reduced and oxidized ascorbate as determinants of membrane permeation. AB - The oil/water distribution coefficients of ascorbic acid and dehydro-L-ascorbic acid have been determined and compared with values for mannitol and lauric acid. In general, the relative degrees of hydrophobicity of the compounds evaluated are lauric acid much greater than mannitol approximately equal to dehydro-L-ascorbic acid greater than ascorbic acid. These findings and recent reports from transport studies do not support the concept that dehydro-L-ascorbic acid is very hydrophobic and crosses cell membranes rapidly by simple diffusion. PMID- 3103696 TI - Isolation and characterisation of goat C-reactive protein. AB - A pentraxin was isolated from acute phase goat serum by its calcium-dependent affinity for agarose, and although it did not bind to phosphorylcholine immobilised on Sepharose, its binding to agarose was reversed by exposure to fluid phase phosphorylcholine. It was identified as goat C-reactive protein on the basis of its immunochemical cross-reactivity with human and bovine C-reactive protein. The molecule was composed of five identical, glycosylated, non covalently associated subunits, each of molecular weight approx. 24,000. Acute phase serum levels in a small number of samples were not significantly different from normal levels (means 72 and 55 micrograms/ml, respectively), suggesting that goat C-reactive protein is not a major acute phase reactant. No other pentraxin was detected in goat serum. PMID- 3103697 TI - Abrogation of the effects of aphidicolin on NIH3T3 and V79 cells by caffeine. AB - In this communication I show that caffeine (1,3,7-trimethylxanthine) stimulates [3H]thymidine incorporation in aphidicolin-treated V79 and NIH3T3 cells. Flow microfluorometric analysis showed that caffeine, partially or fully, abrogates the cell cycle progression block produced by aphidicolin. Increased cell growth is also observed in cultures treated with both aphidicolin and caffeine compared to cultures treated with aphidicolin only. Microscopic examination of V79 cultures treated with aphidicolin for 8 h showed a marked reduction in the frequency of round mitotic cells, as is expected from a drug which inhibits progression through the cell cycle by inhibiting DNA replication; this effect of aphidicolin was also reduced by caffeine. Biochemical analysis showed that caffeine did not directly interfere with the inhibition of DNA polymerase-alpha by aphidicolin. Analysis of dNTP pools indicated that caffeine increased the level of dCTP in V79 cells. In aphidicolin-treated V79 cells, the increase in the dCTP level due to exogenous cytidine was almost completely blocked; caffeine also substantially overcame this effect of aphidicolin. These results indicate that caffeine produces its effects on aphidicolin-treated cells by altering the dCTP metabolism. PMID- 3103698 TI - Secretion of oxytocin and progesterone by ovine corpora lutea in vitro. AB - The mechanisms involved in the control of oxytocin and progesterone secretion by the ovine corpus luteum have been investigated in vitro using luteal slice incubations. Oxytocin and progesterone were secreted at constant rates from luteal slices for 2 h of incubation (366 +/- 60 pg X mg X h and 18.9 +/- 0.18 ng X mg X h, respectively). Secretion of progesterone, but not of oxytocin, was significantly (p less than 0.02) stimulated in the presence of ovine luteinizing hormone. Incubation of luteal slices in medium containing 100 mM potassium, however, resulted in increased secretion of oxytocin and, to a lesser extent, of progesterone (294 +/- 59% and 142 +/- 15%, respectively, p less than 0.05). Basal oxytocin secretion was reduced during incubation in calcium-free medium, compared to secretion in the presence of calcium (70 +/- 15 and 175 +/- 25 pg X mg X 20 min, respectively, p less than 0.01), whereas progesterone secretion was not altered in the absence of calcium. Secretion of both hormones by luteal slices was stimulated by the addition of the calcium ionophore A23187 (p less than 0.05). Addition of prostaglandin F2 alpha (2.8 microM) had no effect on secretion of either oxytocin or progesterone. We have demonstrated that oxytocin and progesterone can be stimulated, independently, from corpus luteum slices incubated in vitro. The pattern of release is consistent with the proposal that oxytocin, but not progesterone, is associated with and actively released from luteal secretory granules. Our results also indicated that prostaglandin F2 alpha does not directly stimulate release of oxytocin or progesterone from luteal cells in vitro. PMID- 3103699 TI - Role of progesterone in the modulation of the preovulatory surge of gonadotropins and ovulation in the pregnant mare's serum gonadotropin-primed immature rat and the adult rat. AB - The role of progesterone in the regulation of the preovulatory surge in gonadotropins and ovulation was examined in this study by use of a potent antagonist of progesterone, RU 486 (17 beta-hydroxy-11 beta-[4-dimethyl aminophenyl]-17 alpha- [prop-1-ynyl]estra-4,9-diene-3-one). The immature rat primed with pregnant mare's serum gonadotropin (PMSG) and the cycling adult animal were the models used to verify the role of progesterone. When RU 486 (200 micrograms/rat) was given as a single dose on the morning of proestrus, there was a significant reduction in the preovulatory surge levels of gonadotropins and ovulation in both animal models. Serum progesterone levels in both models at the time of death on the evening of proestrus were unaltered upon treatment with RU 486. RU 486 did not have any effect on gonadotropin levels in immature rats 7 days after castration. These results show that the actin of RU 486 on the preovulatory gonadotropin surge is due to an antagonism of the action of progesterone on the hypothalamic-pituitary axis. Thus, a role for progesterone in modulating the preovulatory surge of gonadotropins and, consequently, ovulation is strongly suggested. PMID- 3103700 TI - Reproductive effects of olfactory bulbectomy in the Syrian hamster. AB - The effects of olfactory bulbectomy on circulating gonadotropin, prolactin and testosterone levels and on the testicular and pituitary responses to shortening of day length were studied in Syrian hamsters. Adult animals maintained on a 14L:10D cycle were sham-operated or sustained bilateral radical olfactory bulbectomies by aspiration to remove the main and accessory olfactory bulbs and the adjacent regions of the anterior olfactory nucleus. They were then maintained either on the long photoperiod or housed on a 10L:14D cycle. Testicular length was measured at weekly intervals over a 5-mo period. Sham-operated controls exhibited the normal pattern of testicular regression and eventual recrudescence on the short photoperiod. Testicular regression was significantly reduced in bulbectomized animals. Many of these animals showed no regression; others exhibited a reduced degree and/or shortened duration of regression. Serum levels of follicle-stimulating hormone (FSH) were substantially elevated in bulbectomized males maintained in long days. Their serum levels of luteinizing hormone (LH), prolactin and testosterone remained within the range for shams on long photoperiod. In short days, the bulbectomized animals showed the normal, pronounced decline in circulating prolactin levels. Serum FSH and LH levels also showed substantial declines, but the FSH levels were not reduced below the range for controls in long days, and the decline in LH levels was not as great as that for controls in short days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103701 TI - Involvement of lipoxygenase products of arachidonic acid metabolism in bovine luteal function. AB - A series of experiments was conducted to determine the effects of lipoxygenase products of arachidonic acid (AA) metabolism on the function of the bovine corpus luteum (CL). In the first experiment, reaction products of soybean lipoxidase-AA were added to dispersed bovine luteal cells in increasing concentrations. These lipoxygenase products resulted in a dose-related reduction in the biosynthesis of progesterone and 6-keto-prostaglandin (PG)F1 alpha, while the synthesis of PGF2 alpha was unaffected. In a second experiment, the addition of 5 hydroxyeicosatetraenoic acid (5-HETE), a specific lipoxygenase product, again resulted in a reduction in progesterone and 6-keto-PGF1 alpha, with no change in PGF2 alpha synthesis. Extremely high endogenous concentrations of 5-HETE were measured in luteal tissues (36 +/- 17 to 46 +/- 13 ng/10(6) cells) in a third experiment. In the fourth experiment, an inhibitor of the lipoxygenase pathways, nordihydroguaiaretic acid (NDGA) infused into the uterine lumen twice daily on Days 14-18 of the estrous cycle delayed luteolysis and resulted in lengthened estrous cycles (27.2 +/- 0.3 vs 21.5 +/- 1.0 days for controls, p less than 0.05). Thus, an inhibitor of the lipoxygenase pathway of arachidonic acid metabolism delays luteolysis, possibly by removing the preferential inhibition of PGF1 alpha biosynthesis caused by 5-HETE and other products of the lipoxygenase system. Collectively, these results suggest that products of the lipoxygenase pathway are involved in luteolysis in normal heifers. PMID- 3103702 TI - Plasma membranes from rat Sertoli cells: purification and properties. AB - A method is reported for preparing surface (plasma) membranes from rat Sertoli cells. The procedure is based upon homogenization in hypotonic buffer, extraction in a two-phase system, and sedimentation through two sucrose density gradients. The purified membranes consist of large sheets of membrane. The identity and purity of the membranes was demonstrated by electron microscopy, enzyme markers, and functional activities associated with the membranes (binding of follicle stimulating hormone [FSH] and production of cyclic adenosine 5'-monophosphate [cAMP]. Electron microscopy showed membranes with small fragments of cytoplasm attached to the inside of the membrane sheets. Marker enzymes for plasma membrane (5'-nucleotidase and alkaline phosphatase) showed more than 16- and 6-fold enrichment, respectively, and other enzymes showed that contamination by nuclei, mitochondria, endoplasmic reticulum, or cytosol was negligible. Binding of FSH was found to be specific, with KD 1.2 nM and the equivalent of 7500 sites per cell. This binding was enriched 20-fold compared to whole homogenate. Production of cAMP by membranes was increased by addition of FSH and by forskolin to the purified membranes in vitro. PMID- 3103703 TI - Effects of altrenogest and exogenous gonadotropins on ovarian function and embryo recovery in swine leukocyte antigen inbred miniature swine as influenced by cystic endometrial hyperplasia. AB - Altrenogest (ALT), a synthetic progestogen, and exogenous gonadotropins were administered to the Swine Leukocyte Antigen (SLA) inbred miniature pig that typically has a reduced ovulation rate and small litter size. In Study 1, 15 adult female pigs were either controls (Group I, n = 5), fed 15 mg ALT/day for 14 days (Group II, n = 5), or fed ALT and treated with pregnant mare's serum gonadotropin (1200 IU, i.m.) and human chorionic gonadotropin (500 IU, i.m.) 24 h and 104 h, respectively, after ALT withdrawal (Group III, n = 5). In Study 2, three groups of pigs (I, n = 24; II, n = 11; III, n = 11) were treated similarly to those in Study 1 except that pigs in Study 2 (Groups II and III) were mated. Ovaries of all animals in both studies were examined laparoscopically or by laparotomy 5-8 days after estrus to assess ovarian activity. The uteri of Group II and III animals in Study 2 were flushed with tissue culture medium, which was evaluated for the presence and quality of embryos. No pig demonstrated estrous behavior during ALT administration. Not all animals demonstrated typical estrous behavior after ALT withdrawal. When the data from both studies were combined, 2 of 16 (12.5%) of group II and 6 of 16 (37.5%) of Group III pigs failed to demonstrate standing estrus. Following ALT withdrawal, females in Groups II and III returned to estrus in 5.6 +/- 0.3 and 5.8 +/- 0.3 days, respectively (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103704 TI - Viscosity dependence of the solute quenching of the tryptophanyl fluorescence of proteins. AB - We have studied the viscosity dependence of the acrylamide quenching of the fluorescence on the internal tryptophan residues in cod parvalbumin and ribonuclease T1, as well as the model systems. N-acetyl-L-tryptophanamide and glucagon. For the latter systems, the apparent rate constant, kq(app), for acrylamide quenching shows a typical diffusion-limited behavior. For parvalbumin and ribonuclease T1, however, the viscosity dependence of kq(app) is quite different. There is little change in the kq(app) values on increasing the bulk viscosity from 1 to 10 cP (by addition of glycerol), but a further increase from 10 to 100 cP results in a significant reduction in the kq(app). Both an unfolding mechanism and a quencher penetration mechanism are considered to explain the results. Only the penetration mechanism is found to be consistent, and our data are interpreted as indicating that the rate-limiting step for quenching goes from being that of diffusion through the protein matrix, at low viscosity, to diffusion through the bulk solvent, at high viscosity. By also considering the Kramers' relationship in fitting our data, we are able to obtain insight regarding the coupling between internal fluctuations in the structure of the protein and motion of the bulk solvent. For parvalbumin and ribonuclease T1, the internal dynamics are found to be very weakly coupled to the bulk. PMID- 3103705 TI - Calcium induced potassium efflux in erythrocytes of marine teleosts. AB - The effect of the calcium-ionophore A23187+ Ca++ on the K+ transport in the intact erythrocytes of sea-water fishes was investigated. A23187+ Ca++ induced a significant increase in the cell-membrane permeability for potassium ion, while A23187+ Mg++ was ineffective. Addition of EGTA to the medium blocked the ionophore+ Ca++ effect. Quinidine inhibited the A23187+ Ca++-induced K+ transport in the nucleated fish red cell. Propranolol is effective in the fish RBC in presence of Ca++ and EGTA. The relationship of the calcium-induced alkali cation transport in nucleated red cell to that in human red cell is discussed. PMID- 3103706 TI - Proteoglycan-collagen interactions in intervertebral disc. A chondroitin sulphate proteoglycan associates with collagen fibrils in rabbit annulus fibrosus at the d e bands. AB - Rabbit annulus fibrosus and nucleus pulposus were analysed for hydroxyproline, chondroitin sulphate, keratan sulphate and dermatan sulphate. Tissue proteoglycans were stained for electron microscopy with Cupromeronic blue, used in the critical electrolyte concentration mode, with and without prior digestion by chondroitinase AC or ABC, hyaluronidase or keratanase. Collagen bands, a-e were demonstrated with UO2++. A chondroitin sulphate proteoglycan was found orthogonally associated with loosely packed collagen fibrils in annulus fibrosus at the d and e bands. The close metabolic and structural analogies with the dermatan sulphate proteoglycans previously shown to be located at collagen d-e bands in tendon, skin, etc. (Scott and Haigh (1985) Biosci. Rep. 5:71-81), are discussed. Tightly packed annulus collagen fibrils were surrounded by axially oriented proteoglycan filaments, mostly without specific locations. PMID- 3103707 TI - [Quantitative comparison of the cytogenetic effect of thiophosphamide during in vivo and in vitro action on monkey lymphocytes]. AB - Mutagenic in vivo and in vitro effects were compared quantitatively by the investigation of sister chromatid exchange (SCE) rate and chromosomal aberrations caused by thiophosphamide in macaca rhesus lymphocytes. The integral of thiophosphamide concentration in the blood or culture fluid by a certain time period was used for the estimation of the dose of mutagenic exposure. It was shown that the dose-response relationships and corresponding regression coefficients were similar when the in vivo and in vitro results were compared. The data obtained indicate the possibility for quantitative extrapolation of the results obtained in vitro on the entire organism. PMID- 3103708 TI - On the mechanisms of sensitization and attachment of antibodies to RBC in drug induced immune hemolytic anemia. AB - The mechanisms of sensitization and attachment of drug-dependent antibodies to RBC in drug-induced immune hemolytic anemias are largely speculative. Nomifensine has been incriminated in causing immune hemolysis in a large number of patients. The hemolysis was usually of the so-called immune complex type, less commonly of the autoimmune type, and more surprisingly, few patients had developed both types of hemolysis. To determine whether nomifensine (metabolite)-dependent antibodies (ndab) exhibit specificity for antigenic structures of RBC membranes, 30 ndab were tested against large panels of RBC with common and rare antigens. We found that only 14 out of 30 ndab were invariably reactive with all cells tested. Nine antibodies were, similar to the majority of idiopathic or drug-induced autoantibodies, not or only weakly reactive with Rhnull RBC. Three antibodies did not react with cord RBC and could be inhibited by soluble I antigen. The remaining four antibodies gave inhomogeneous reaction patterns or were even negative with selected RBC; their specificity could not be identified. On a Scatchard plot analysis of one ndab, a maximum of 173,000 drug-dependent antibodies of the IgG class can specifically bind per RBC in the presence of the drug. Although nomifensine and its metabolites do not attach tightly onto RBC, our results clearly indicate that RBC do not act as "innocent bystanders," but rather serve as a surface for a loose attachment of drugs that possibly cause a subtle structural change in the cell antigens and, by this means, allow in vivo sensitization; and a specific binding of the resultant antibodies. This concept would explain why these antibodies can be directed against drug-cell complexes, against cell antigens alone (autoantibodies), or against both in the same patient. PMID- 3103709 TI - Cytoplasmic immunoglobulins in chronic lymphocytic leukemia B cells. AB - It is generally assumed that chronic lymphocytic leukemia of B cell origin (B CLL) is characterized by the presence of surface membrane immunoglobulins (SmIg) and by the absence of cytoplasmic immunoglobulins (CyIg). In a variable number of cases SmIg are not detectable because of their low density on the cellular surface. Because a constant presence of CyIg in 20 subjects suffering from B-CLL has been reported recently, we reexamined 15 SmIg-negative and 10 SmIg-positive B CLL patients by SmIg and CyIg determinations. We used a direct immunofluorescence method on peripheral blood mononuclear cells for the detection of SmIg and, after fixation, for CyIg. CyIg were detectable in 24 out of 25 cases, with a fluorescence intensity ranging from weak to moderate. The existence of frequent negative results for CyIg determination in B-CLL reported in the literature probably depends on the low sensitivity of the method used. We conclude that CyIg determination is useful in phenotyping every B-CLL patient, especially SmIg negative ones. PMID- 3103710 TI - Development of T3/T cell receptor gene expression in human pre-T neoplasms. AB - Acquisition of mature T cell function and the T cell antigen receptor repertoire occur in the thymus. In an effort to delineate the cascade of events leading to T cell maturation, we analyzed a series of clonal human precursor T cell neoplasms representing early, middle, and late stages of intrathymic differentiation. Rearrangements of the T cell receptor beta and gamma genes appear concurrently and are preceded by surface expression of the 3A1 (CD7) molecule. Subsequent transcription of the beta gene is coordinated with surface expression of T1 (CD5) and T11 (CD2), transcription of T3 delta mRNA, and the appearance of intracellular T3 (CD3) protein. As late events, T alpha gene transcripts appear and, finally, T3, the multichain complex linked to the T cell receptor, is presented on the cell surface. Findings reported here provide a model of the developmental orchestration of genes encoding antigen recognition in human T cells. PMID- 3103711 TI - Early T cell differentiated chronic myeloid leukemia blast crisis with rearrangement of the breakpoint cluster region but not of the T cell receptor beta chain genes. AB - Early T cell differentiation is described in a case of Philadelphia chromosome positive chronic myeloid leukemia (CML) in blast crisis, supporting multi-lineage differentiation potential of CML precursor cells. In the absence of myeloid markers, strong positivity for terminal deoxynucleotidyl transferase (TdT) and reactivity with T cell antibody 3A1, but lack of more mature T cell antigens, provided evidence for immature T cell differentiation. Molecular analysis of the breakpoint cluster region (bcr) in chromosome 22 revealed a rearrangement and thus confirmed the CML origin of the early T cell blasts. T cell receptor beta chain sequences were found in germline configuration and therefore suggest a very immature stage of T cell differentiation in the CML blasts. PMID- 3103712 TI - Mediastinal lymphoma of clear cell type is a tumor corresponding to terminal steps of B cell differentiation. AB - This article reports eight primary mediastinal tumors occurring in young adults (19 to 43 years, mean 29.4 years), predominantly female (six of eight) adults. Most patients responded badly to aggressive therapy. Progression is presently noted in one patient; five patients died 10, 11, 13, 18, and 22 months after diagnosis. No patient developed leukemia. The tumors were highly proliferative, had a diffuse growth pattern, and comprised clear cells of variable size. They could not be classified histologically, but could, however, be immunohistologically characterized as B cell lymphomas. In all cases, the immunophenotype was LC+, cALLa-, CD19+, CD20+, CD21-, Ig (surface/cytoplasm)-, and PC-1+. In addition, the neoplastic cells exhibited variable defects in the expression of HLA-A,B,C and HLA-DR and inconstant expression of other B cell restricted/associated antigens. This combination of immunophenotypical and clinical features suggests that the mediastinal clear cell lymphoma (MCCL) is a previously undescribed type of B cell lymphoma corresponding to the terminal steps of B cell differentiation. PMID- 3103713 TI - The regulatory role of interleukin 2-responsive T lymphocytes on human marrow granulopoiesis. AB - The effect of recombinant interleukin 2 (IL2) on marrow CFU-C colony formation was evaluated to define the role for T lymphocytes in human marrow granulopoiesis. The colony-stimulating factor (CSA) used in our experiments was found to contain IL2. IL2 depletion from CSA resulted in a reduction in CFU-C colony proliferation. Addition of exogenous IL2 caused an increase in CFU-C colony numbers in a dose-dependent manner. This increase could be prevented by anti-Tac, a monoclonal antibody (MoAb) to the IL2 receptor. Moreover, anti-Tac in the absence of exogenous IL2 resulted in an overall decrease in colony numbers. Depletion of either adherent cells or T lymphocytes abolished the effect of IL2 and anti-Tac on colony growth. In the presence of IL2, re-addition of T lymphocytes to the T-depleted marrow or adherent cells to adherent cell-depleted marrow resulted in a significant increase in CFU-C colony numbers, whereas no significant effect was found when IL2-depleted CSA was used. Although T lymphocytes were not themselves essential for CFU-C colony growth, our studies indicate that IL2 and IL2-responsive T cells can regulate in vitro granulopoiesis. PMID- 3103714 TI - Membrane receptors for interleukin 2 on hematopoietic precursors in chronic myeloid leukemia. AB - In this report we present data on the expression of IL2 receptors on chronic phase CML cells. Using an anti IL2 receptor monoclonal antibody (McAb aIL2r) in indirect immunofluorescence we found significant proportions (42.2% +/- 19.7 SD) of the CML cells (previously depleted of E rosetting T cells) to be IL2 receptor positive following incubation in suspension for 18 hours at 37 degrees C. Noninduced cells did not express IL2 receptors. After induction the aIL2r positive and negative cell subpopulations were sorted and analyzed separately for morphology, lineage specific cell surface markers, and clonogenic cell numbers. The IL2 receptor positive CML subpopulations mainly contained blast cells and monocytes and revealed reactivity with myeloid McAbs but not with T cell, B cell, platelet, or erythroid markers. Clonogenic cells (CFU-GEMM, BFUe, and CFU-GM) were selectively recovered from aIL2r positive CML cells and thus were IL2 receptor positive. The addition of recombinant IL2 (rIL2) to CFU-GM and BFUe cultures, in concentrations from 50 to 500 U/mL, did not influence the efficiency of colony formation. Binding of a radiolabeled IL2 preparation to the in vitro activated CML cells indicated the presence of low affinity receptors for IL2. In contrast to CML, normal human marrow cells were consistently aIL2r nonreactive. Thus, IL2 receptor inducibility is a characteristic feature of CML clonogenic cells, which they share with AML, but not with normal marrow progenitors. The role of IL2 receptors in the regulation of proliferation of CML cells requires further investigation. PMID- 3103715 TI - Further studies of the secretory pathway in thrombin-stimulated human platelets. AB - The pathway followed by secretory products stored in platelet alpha granules during the release reaction remains controversial. Tannic acid has been used in the present study as an electron-dense stain to follow the secretory process in thrombin-stimulated platelets. Preliminary experiments demonstrated that tannic acid precipitates fibrinogen, and binds osmium tetroxide to fibrinogen and fibrin strands. Examination of platelets fixed at short intervals after exposure to thrombin and incubated in solutions containing tannic acid revealed electron dense deposits of osmium not apparent in resting platelets. Granules and lumina of channels making up the open canalicular system (OCS) were unstained in discoid cells. However, exposure to thrombin at concentrations of 1 to 5 U/mL for thirty seconds or more resulted in intense staining of alpha granules by osmium. Some granules communicated directly with dilated channels of the OCS, and several were frequently connected to the same canaliculus. The electron-dense substance in swollen granules and channels appeared to be in the process of extrusion through narrow or dilated openings of the OCS onto the platelet surface. Granule-to granule fusion and formation of sealed vacuoles of fused granule products unstained by tannic acid-osmium were not observed. The findings support the concept that secretion by stimulated human platelets results from development of direct communications between granules and channels of the OCS and subsequent extrusion of products through channel pores to the surrounding medium. PMID- 3103716 TI - The syndrome of T8 hyperlymphocytosis: variation in phenotype and cytotoxic activities of granular cells and evaluation of their role in associated neutropenia. AB - We performed a longitudinal study of the phenotype and functions of granular lymphoid cells from seven patients with T8 hyperlymphocytosis and neutropenia. Whereas cells retained a T3+ T8+ (six cases) or T3- T8+ (one case) phenotype at different examinations, the expression of natural killer (NK)-related antigens (HNK1- and Leu11-defined antigens) exhibited striking variations, some of which were also observed after in vitro culture. Similarly, natural or antibody mediated cytotoxic activities fluctuated in vivo and in vitro. Cells from the patient with T3- T8+ proliferation were able to inhibit directly the growth of early CFU-GM, CFU-E, and BFU-E and to a lesser extent of late CFU-GM, as shown by cultures of autologous blood or marrow progenitors after depletion (and subsequent addition) of granular cells. In the other six patients with T3+ T8+ cells, no such effect was found. However, after a 24-hour incubation of the progenitors with the granular cells, CFU-GM growth was clearly inhibited; this was not observed in all experiments, a finding which may be related to the spontaneous variations of cell killer functions. Finally, no correlation was noted between the clinical course or extent of lymphoid proliferation and cell function or phenotype or with the monoclonal (two cases), polyclonal (three cases) or germ-line (one case) patterns of T cell receptor beta gene configuration. PMID- 3103717 TI - Retinoic acid cooperates with tumor necrosis factor and immune interferon in inducing differentiation and growth inhibition of the human promyelocytic leukemic cell line HL-60. AB - In this study, we analyzed the effect of tumor necrosis factor (TNF) on retinoic acid (RA)-induced myeloid differentiation of the promyelocytic HL-60 leukemia cell line. We show that low concentrations of the two substances, almost inactive in inducing differentiation when used separately, induce differentiation when added simultaneously to the cell cultures. Cells simultaneously expressing both monocyte/macrophage phenotype (typically induced by TNF) and granulocyte characteristics (typically induced by RA) are induced by a combination of the two factors, indicating that TNF and RA potentiate each other's activity. The results obtained using immune interferon (IFN-gamma) in combination with the two inducers suggest that the mechanism of action of TNF and IFN-gamma are possibly different. The inhibitory effect of RA on the expression of HLA class I antigens and of the high-affinity Fc receptor is potentiated by TNF but completely reversed by rIFN gamma. PMID- 3103718 TI - Pattern of expression of HLA-DR and HLA-DQ antigens and mRNA in myeloid differentiation. AB - We examined the expression of HLA-DR and HLA-DQ antigens and mRNA from myeloid and lymphoid cells obtained from normal volunteers and established cell lines. Cytofluorometric analysis and immunoprecipitation were performed using murine monoclonal antibodies specific for HLA-DR (L-243) and HLA-DQ (Leu 10). The expression of mRNA for HLA-DR and HLA-DQ chains was determined by Northern blot and RNA dot-blot analysis. Lymphoid cell lines expressed both HLA-DR and HLA-DQ antigens, with consistently higher levels of expression of DR. Myeloid cell lines of early myeloblast or bipotent (myeloid-erythroid) phenotype (KG-1, KG-1a, HEL) expressed HLA-DR at high levels, whereas cell lines manifesting a greater degree of myeloid maturation (ML-3, HL-60, U937) expressed DR at low or undetectable levels. The HLA-DQ antigen was expressed at low levels on the surface of KG-1 and KG-1a cells but was not detectable on other myeloid cell lines. The expression of mRNA for HLA-DR and HLA-DQ chains paralleled the pattern of expression of the respective antigens. The HL-60 and U-937 cells stimulated to differentiate in vitro to macrophages with 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] were induced to express detectable levels of HLA-DR antigens. Exposure to gamma-interferon (gamma IFN) increased the expression of HLA-DR antigens by all myeloid cell lines. Induction of differentiation in vitro with either 1,25(OH)2D3 or dimethyl sulfoxide potentiated this effect of gamma-IFN. Expression of the HLA-DQ antigens was increased on KG-1 myeloblasts after exposure to gamma-IFN. HLA-DQ expression could not be detected on other myeloid cell lines after exposure to gamma-IFN, nor was HLA-DQ expression stimulated by gamma-IFN after HL-60 and U-937 cells were induced to differentiate to macrophagelike cells in vitro. These results provide additional evidence that expression of the HLA-DR and HLA-DQ genes may be independently regulated in human myeloid cells. PMID- 3103719 TI - Mutations in N-ras predominate in acute myeloid leukemia. AB - Using synthetic oligomers we investigated fresh samples of acute myeloid leukemia (AML) for the presence of mutated ras oncogenes. Our original results showed that five of eight samples contained a mutation in codon 13 of the N-ras gene. In a subsequent study involving 37 samples, we found only one N-ras-13 mutation, and, in addition, mutations in codon 61 of the N-ras gene in four cases and a mutation in codon 12 of the Ki-ras gene in two cases. Amplification of ras genes was not observed. We conclude that in approximately 20% to 25% of AML cases, a mutated ras oncogene is present, predominantly the N-ras gene. The occurrence of mutations does not correlate with the cytological features of the leukemia. PMID- 3103720 TI - In vitro tests that predict tumor-associated idiotype levels in the serum of patients with B cell lymphomas and leukemias. AB - The presence of circulating tumor idiotype interferes with the in vivo effectiveness of anti-idiotype antibodies. We developed two assays that permit identification of patients with high levels of serum idiotype without the need for first producing an anti-idiotype antibody. A cell suspension made from the tumor was cultured for seven days with or without phytohemagglutin (PHA) and/or phorbol myristic acetate (PMA). Ig secretion in vitro by patients' tumor cells varied. In 4 patients, no secretion in vitro occurred, 5 patients had low levels, and 5 patients had high levels of Ig secretion. In three patients, Ig secretion occurred only after stimulation with PHA, PMA, or both. Spontaneous or induced immunoglobulin secretion in vitro is related to the levels of tumor idiotype secretion that exist in vivo. Eight patients with serum idiotype levels greater than 100 micrograms/mL (mean 265 micrograms/mL), had a minimum of 1.0 microgram/10(6) cells of idiotype secretion in vitro. Nine patients with serum idiotype levels less than 30 micrograms/mL (mean 3.7 micrograms/mL), had less than or equal to 0.5 microgram/10(6) cells of idiotype secretion in vitro. In another assay, the levels of IgM kappa and IgM lambda in patients' sera were compared with those in normal serum. An imbalance in the relative amounts of IgM kappa and IgM lambda indicated high levels of circulating idiotype in the serum, but this assay was less sensitive than the in vitro secretion assay and limited to IgM-secreting tumors. These assays will be useful for future clinical studies using anti-idiotype antibodies. PMID- 3103721 TI - Establishment and characterization of a cell line, TOM-1, derived from a patient with Philadelphia chromosome-positive acute lymphocytic leukemia. AB - A new Philadelphia chromosome (Ph1)-positive cell line, designated TOM-1, was derived from bone marrow cells of a patient with Ph1-positive acute lymphocytic leukemia (ALL). The TOM-1 cells were positive for Ia and B1 antigens and terminal deoxynucleotidyl transferase (TdT) but negative for common ALL antigen. Although neither surface Ig nor cytoplasmic Ig was detected, the TOM-1 cells contained rearranged immunoglobulin-H chain genes but retained germ-line kappa chain and germ-line T cell receptor beta-chain genes. These results indicate that the TOM-1 cells reside as the progenitor of pre-B cells. We have investigated the chromosome 22 breakpoint and c-abl gene expression in the TOM-1 cells. We found that the breakpoint on chromosome 22 was within the breakpoint cluster region (bcr) in the TOM-1 cells. We also found the breakpoints within or near bcr in four of six Ph1-positive ALL cases, similar to the findings in Ph1-positive CML cases. Amplification of the c-abl gene was not detected in the TOM-1 cells. The leukemic cells isolated from a patient with CML in myeloid crisis contained a novel 8-kilobase (kb) abl-related messenger RNA (mRNA), but the TOM-1 cells contained c-abl transcripts of only normal sizes, despite the fact that they showed the bcr gene rearrangement. PMID- 3103723 TI - T-cell prolymphocytic leukemia (T-PLL) with unique surface phenotype. AB - Leukemic cells of a 19 year old patient with prolymphocytic leukemia of T-cell type (T-PLL) were characterized by surface markers and immunologic functions. Phenotypic analysis using a large panel of monoclonal antibodies corresponding to the clusters (CD) of differentiation antigens established on the Leukocyte Typing Workshops I and II revealed a unique T-cell phenotype not yet reported in the literature: CD1 (T6)-, CD2 (T11)+, CD3 (T3)+, CD4 (T4)-, CD5 (T1)-, CD6 (T411)+, CD7 (Leu9)+, CD8 (T811)-, CD10 (J5)-, CD11 (M22)+, CD12 (M67)-, CD13 (My7)-, CD14 (Mo2)-, CD16 (Vep13, 3G8, Leu11)+, CD18 (MHM23)+, CD19 (B4)-, CD20 (B1)-, CD25 (TAC)-, MHC-class II (HLA-DR, HLA-DQ)-, NKH1A+, Leu7-. Despite the expression of surface structures associated with natural killer (NK) function (CD16, CD18, NKH 1 A) the T-PLL cells were inactive in NK assays in vitro. Low in vitro ADCC activity was detectable. This unusual T-PLL phenotype might help to identify a new distinct T-cell differentiation stage. PMID- 3103722 TI - Diagnostic and prognostic value of immunohistological bone marrow examination: results in 212 patients with lymphoproliferative disorders. AB - Cryostat sections of 246 consecutive bone marrow biopsies from 212 patients with lymphoproliferative disease were investigated using a panel of monoclonal antibodies (MOAb's) and an immunoperoxidase technique. Bone marrow involvement was demonstrated by immunohistological examination in 121/160 patients (76%) with non-Hodgkin lymphomas (NHL) and 16/23 patients (70%) with plasma cell malignancies; the definite immunological diagnosis could be performed in 77% and 88%, respectively. Reactivity with the MoAb Ki-67 correlated with clinical parameters: in all cases exhibiting more than 5% positive cells an unfavourable course was seen, independent of the histological subtype. Another MoAb of potential prognostic relevance is KiM 4 b, which reacts with follicular dendritic cells (FDC). Besides the presence of FDC in germinal center tumors (CB/CC and CC NHL) we found FDC in a minority of cases with B-CLL (5/44) and IC lymphoma (4/18). In the latter group 3/4 patients showed a favourable clinical course (vs 2/14 without FDC). The MoAb Tu 1 could discriminate between the lymphoplasmocytoid (11/12 positive) and the lymphoplasmocytic (0/6 positive) subtype of IC lymphoma and has proven of diagnostic importance. Expression of IL 2 receptors, detected by MoAb anti-Tac (CD 25), was demonstrated on leukemic cells from patients with hairy cell leukemia (100%), B-CLL (82%), IC (61%), CC (50%) and CB/CC lymphoma (50%). A considerable number of reactive T-lymphocytes (5%-60% of tissue cells) were identified among the neoplastic B cells with a predominance of CD4+ cells in most cases with NHL, whereas the CD4+/CD8+ ratio was significantly lower in myelomas and non-infiltrated bone marrows. The potential meaning of these findings is discussed. The immunohistological bone marrow analysis represents an important additional method in the diagnostic procedures of lymphoproliferative diseases involving the bone. PMID- 3103724 TI - Intensive care: a specialty or a branch of anaesthetics? PMID- 3103725 TI - Alcohol in industry. PMID- 3103726 TI - Barrett's oesophagus. PMID- 3103727 TI - Depression in children. PMID- 3103728 TI - Bone marrow transplantation in precocious osteopetrosis. PMID- 3103729 TI - Effect of chloroquine on insulin and glucose homoeostasis in normal subjects and patients with non-insulin-dependent diabetes mellitus. AB - Plasma glucose, insulin, and C peptide concentrations were determined after an oral glucose load in normal subjects and in a group of patients with non-insulin dependent diabetes mellitus before and during a short course of treatment with chloroquine. In the control group there was a small but significant reduction in fasting blood glucose concentration but overall glucose tolerance and hormone concentrations were unaffected. In contrast, the patients with non-insulin dependent diabetes mellitus showed a significant improvement in their glucose tolerance, which paralleled the severity of their diabetes. This response seems to reflect decreased degradation of insulin rather than increased pancreatic output. These observations suggest that treatment with chloroquine or suitable analogues may be a new approach to the management of diabetes. PMID- 3103730 TI - Effect of single high dose infusions of aminohydroxypropylidene diphosphonate on hypercalcaemia caused by cancer. AB - Single intravenous infusions of 30 mg aminohydroxypropylidene diphosphonate were given to 16 patients who had malignant hypercalcaemia to assess host tolerance and the effect on serum calcium concentration. Ten of these patients also received intravenous rehydration or corticosteroids, or both. The serum calcium concentrations decreased significantly after treatment with aminohydroxypropylidene diphosphonate. Ten patients became normocalcaemic (normal range, adjusted for serum albumin, 2.25-2.75 mmol/l), two became hypocalcaemic, three showed decreases in serum calcium concentrations of more than 0.75 mmol/l, and one showed a decrease of more than 0.55 mmol/l. Only one patient had a minimum concentration greater than 2.77 mmol/l. Aminohydroxypropylidene diphosphonate was effective in metastatic and non-metastatic hypercalcaemia, and its hypocalcaemic effect was prolonged in some cases. There were no appreciable side effects. Single high dose infusions of aminohydroxypropylidene diphosphonate could replace conventional daily lower dose infusions, but the optimum frequency of high dose infusions remains to be determined. PMID- 3103731 TI - Prospective randomised study of preoperative endoscopic sphincterotomy versus surgery alone for common bile duct stones. AB - One hundred and twenty patients with known common bile duct stones were entered into a prospective randomised study of preoperative endoscopic sphincterotomy and stone clearance (group 1) versus surgery alone (group 2). Five patients were incorrectly entered; the 55 patients randomised to group 1 and the 60 randomised to group 2 were well matched with respect to clinical features and biochemical and medical risk factors. In group 1 endoscopic stone clearance was successful in 50 patients (91%); five of these patients refused elective surgery, though this was subsequently necessary in one. In group 2 common bile duct stones were cleared surgically in 54 of 59 patients (91.5%); one patient was treated by endoscopic sphincterotomy alone because of a myocardial infarct. The overall major complication rate in group 1 was 16.4% and included two deaths; in group 2 this was 8.5% and included one death. The minor complication rate in group 1 was 16.4% and that in group 2 13.6%. These differences in outcome were not significant. Despite a significant reduction in total hospital stay of patients in group 1, these results do not support the routine use of preoperative endoscopic sphincterotomy in patients having biliary surgery for stones in the common bile duct. PMID- 3103732 TI - 75 deaths in asthmatics prescribed home nebulisers. AB - The circumstances surrounding the deaths of 75 asthmatic patients who had been prescribed a domiciliary nebuliser driven by an air compressor pump for administration of high dose beta sympathomimetic drugs were investigated as part of the New Zealand national asthma mortality study. Death was judged unavoidable in 19 patients who seemed to have precipitous attacks despite apparently good long term management. Delays in seeking medical help because of overreliance on beta agonist delivered by nebuliser were evident in 12 cases and possible in a further 11, but these represented only 8% of the 271 verified deaths from asthma in New Zealanders aged under 70 during the period. Evidence for direct toxicity of high dose beta agonist was not found. Nevertheless, the absence of serum potassium and theophylline concentrations and of electrocardiographic monitoring in the period immediately preceding death precluded firm conclusions whether arrhythmias might have occurred due to these factors rather than to hypoxia alone. In most patients prescribed domiciliary nebulisers death was associated with deficiencies in long term and short term care similar to those seen in patients without nebulisers. Discretion in prescribing home nebulisers, greater use of other appropriate drugs, including adequate corticosteroids, and careful supervision and instruction of patients taking beta agonist by nebuliser should help to reduce the mortality from asthma. PMID- 3103733 TI - Exceptional virilisation due to ovarian tumour and reversal after resection. PMID- 3103734 TI - Fall and rise of immunity to rubella. PMID- 3103735 TI - Eye injuries caused by directed jets of water from a fire hose. PMID- 3103736 TI - Pulsatility of luteinising hormone in men with chronic renal failure: abnormal rather than absent. PMID- 3103737 TI - Does sulphoxidation state predict gold toxicity in rheumatoid arthritis? PMID- 3103738 TI - Acute pancreatitis: a new finding in cryptosporidium enteritis. PMID- 3103739 TI - Isolation of human immunodeficiency virus from synovial fluid of a patient with reactive arthritis. PMID- 3103740 TI - Open access to orthopaedic appliances for general practitioners. AB - A clinic to which general practitioners can refer patients for some types of orthopaedic appliances was opened in North Clwyd in 1983. During 1985, 956 patients were referred by 82 general practitioners; 860 patients received an appliance, and the average waiting time was less than five weeks. Most referrals were for soft collars (44%), lumbar sacral supports (30%), and dorsilumbar supports (7%). Thirty eight patients failed to attend, 54 declined an appliance, and four referrals were considered to be inappropriate. A few patients were subsequently referred to consultant outpatient clinics, 22 for physiotherapy and 34 were referred simultaneously to the open access clinic. The referral rates for general practitioners with access to community hospitals were low. Such an arrangement merits wider consideration. PMID- 3103741 TI - Recurrence after surgical treatment of hidradenitis suppurativa. AB - From six to 89 months after surgery 82 patients who had been treated by radical surgery (118 excisions) for intractable hidradenitis suppurativa were reviewed. Local recurrence rates varied greatly with the disease site, being low after axillary (3%) and perianal surgery (0%) and high after inguinoperineal (37%) and submammary (50%) excision. Recurrence results from inadequate excision or an unusually wide distribution of apocrine glands, but physical factors such as obesity, local pressure, and skin maceration played a part in a few patients. Recurrence due to inadequate surgery tended to be the most troublesome. At follow up 75 (91%) of the patients were pleased with the results of their operation. A quarter of the patients developed disease at a new anatomical site after operation. Radical surgery gives good symptomatic control of severe hidradenitis suppurativa of the axilla, inguinoperineal, and perianal regions but is less satisfactory for submammary disease. PMID- 3103743 TI - Health care for travellers: one year's experience. PMID- 3103742 TI - Anatomy and subversion: 150th anniversary of Georg Buchner's death. PMID- 3103744 TI - Identity cards for patients infected with HIV? AB - Dr A C Srivastava has written to us to describe a case that raises the suggestion that people infected with the human immuno-deficiency virus (HIV) should carry identity cards. We asked two physicians, a general practitioner working with patients with the acquired immune deficiency syndrome (AIDS), and a general practitioner with a special interest in medical ethics to respond to the broad issues raised by Dr Srivastava's letter. PMID- 3103745 TI - Prescribing in pregnancy. Epilepsy and anticonvulsant drugs. PMID- 3103747 TI - Alcohol in New Zealand. PMID- 3103746 TI - Portraits from memory. 7--Dr E C (Ted) Smith (d 1943). PMID- 3103748 TI - How can good general practitioner care be achieved? PMID- 3103749 TI - Early emergency care. PMID- 3103750 TI - Unemployment and mortality. PMID- 3103751 TI - Reflections on death in childhood. PMID- 3103752 TI - Junior staff and waiting lists. PMID- 3103753 TI - Mozart ear and Mozart death. PMID- 3103754 TI - Future of the pathologist in an era of technological change and cost containment. PMID- 3103755 TI - From New to old England: the progress of Lyme disease. PMID- 3103756 TI - Continued medical education must not be an optional extra. PMID- 3103757 TI - Late abortion. PMID- 3103758 TI - Gastric cancer, diet, and nitrate exposure. PMID- 3103759 TI - Juvenile intestinal polyps--are they always benign? PMID- 3103760 TI - Funding the universities. PMID- 3103761 TI - Moderate sodium restriction with angiotensin converting enzyme inhibitor in essential hypertension: a double blind study. AB - Fifteen unselected patients who had essential hypertension and whose average supine blood pressure when they were not receiving any treatment and their usual sodium intake was 162/107 mm Hg were treated with captopril 50 mg twice daily. After one month's treatment their supine blood pressure had decreased to 149/94 mm Hg. They were then instructed to reduce their sodium intake to about 80 mmol(mEq)/day. After two weeks of moderate sodium restriction they were entered into a double blind randomised crossover study comparing the effect of 10 Slow Sodium tablets (100 mmol sodium chloride) with matching placebo tablets while continuing to take captopril and restrict sodium in their diet. After one month of taking placebo their mean supine blood pressure was 137/88 mm Hg with a urinary sodium excretion of 83 mmol/24 h, while after one month of taking Slow Sodium tablets their mean supine blood pressure was 150/97 mm Hg (p less than 0.001) with a sodium excretion of 183 mmol/24 h. The mean supine blood pressure during moderate sodium restriction therefore decreased by 9% and correlated significantly with the reduction in urinary sodium excretion. These results suggest that the combination of treatment with a moderate but practical reduction in sodium intake and an angiotensin converting enzyme inhibitor is effective in decreasing the blood pressure in patients with essential hypertension. This combined approach overcomes some of the objections that have been made to salt restriction alone and to converting enzyme inhibitors alone. PMID- 3103762 TI - Are we drinking our neurones away? AB - A quantitative neuropathological necropsy study of the human cerebral cortex showed that the number of cortical neurones in the superior frontal cortex in chronic alcoholic patients is significantly reduced compared with that in controls matched for age and sex. The number of neurones in the motor cortex did not differ significantly between the controls and alcoholics, but in both cortical regions there was evidence that alcoholic patients had smaller (shrunken) neurones than controls. Further studies are necessary to identify other regions of the cerebral cortex that are selectively damaged in brain damage associated with alcohol. PMID- 3103763 TI - Hepatitis B, tropical ulcers, and immunisation strategy in Kiribati. AB - The seroepidemiology of hepatitis B was studied in Kiribati (formerly the Gilbert Islands). Six hundred and two (98%) of the population studied showed evidence of current or previous infection. The prevalence of hepatitis B surface antigen was 31% (188/615) and of the e antigen was 9% (58/615). Infection was acquired early in life, and the prevalence of both antigens declined with age. The rates of infection were similar in all age groups examined (0-70) including early childhood. Both hepatitis B surface antigen and e antigen were detected in exudates from tropical ulcers, which may be a source of environmental hepatitis B. Concordance of antigen presence was higher in pairs of siblings than in mother child pairs. All Gilbertese children should receive hepatitis B vaccine at birth or soon after if the long term consequences of hepatitis B infection are to be minimised. PMID- 3103764 TI - Micturition and the mind: psychological factors in the aetiology and treatment of urinary symptoms in women. AB - The mental state of 211 women attending a urodynamic clinic was assessed using questionnaires. Patients with genuine stress incontinence had scores comparable with other patients with longstanding physical complaints. Patients with sensory urgency were more anxious than those with genuine stress incontinence. Patients with detrusor instability were as anxious as patients with sensory urgency and in addition had higher scores on the hysteria scale. A subset of patients (roughly a quarter of the total) was identified, comprising members of all three diagnostic groups, for whom urinary symptoms rendered life intolerable. These patients were as anxious, depressed, and phobic as psychiatric inpatients, emphasising the serious psychological morbidity experienced by patients with urinary symptoms. Fifty patients with detrusor instability or sensory urgency entered a randomised trial comparing psychotherapy, bladder drill, and propantheline. The psychotherapy group significantly improved on measures of urgency, incontinence, and nocturia, though not on frequency. Bladder training was an effective treatment for frequency and patients became less anxious and depressed. There was a modest improvement in frequency of micturition in patients given propantheline. Frequency may be a learnt disorder which responds to the direct symptom oriented approach of bladder training. Patients with urgency and nocturia predominating might derive more benefit from psychotherapy. PMID- 3103765 TI - Association of placenta praevia and sex ratio at birth. PMID- 3103766 TI - Tolerance to glyceryl trinitrate patches: prevention by intermittent dosing. PMID- 3103767 TI - Immunoscintigraphy of metastases with radiolabelled human antibodies. PMID- 3103768 TI - Rapid progression of a growth hormone producing tumour during dopamine agonist treatment. PMID- 3103769 TI - Hepatitis B: risk to expatriates in South East Asia. PMID- 3103770 TI - Inadequacy of oleic acid in erythrocytes as a marker of malignancies. PMID- 3103771 TI - Three further cases of Lyme disease. PMID- 3103772 TI - Effect of carbonic anhydrase inhibitors on glomerular filtration rate in diabetic nephropathy. PMID- 3103773 TI - Role and responsibilities of general practitioner organisers of continuing medical education. AB - A total of 359 general practitioner organisers of continuing medical education in England and Wales were sent a questionnaire on their role and responsibilities in 1985; 206 with relevant duties replied. The results of the survey showed that they were playing an effective part in planning, organising, and evaluating educational activities at district level, that many were highly qualified and experienced general practitioners, and that many had previously been concerned in vocational training. Less than half had undergone formal training for their continuing education role. Only 105 (51%) were appointed district general practitioner tutors. They were more active in postgraduate centres than in practice based education. Almost a quarter (49) spent three to five hours a week on their educational duties, but 111 (54%) spent fewer hours. Although well provided with educational resources, few had any control over district educational funds, and over half lacked office space. As to remuneration, 161 (78%) received 500 pounds or less a year and almost two thirds received no reimbursement for expenses. Most had no job description. Attention is drawn to the case for appointing general practitioner organisers of continuing medical education ("district general practice tutors") in all districts of England and Wales, to their role in improving the participation of general practitioners in continuing medical education, and to the urgent need for a national agreement on their job description, preparation, support, and remuneration. PMID- 3103774 TI - Syringe driver in terminal care. AB - Continuous subcutaneous infusions of drugs by syringe driver are used often and successfully in the terminal care of patients when drugs cannot be given orally. Diamorphine is the opioid of choice because of its high solubility. If other drugs such as antiemetics, anticholinergics, sedatives, or steroids are required they may also be given by syringe driver. This method is particularly useful for domiciliary care, where the practical difficulties of providing regular parenteral analgesia are otherwise formidable. PMID- 3103775 TI - Plasticized polyvinylchloride as a temporary dressing for burns. AB - Plasticized polyvinylchloride film has been used in this burns unit for a long time for dressings before the ward round, before surgery, and when the burned patient is transferred from the casualty department to the burns unit. Plasticized polyvinylchloride film is easy to use, safe, and causes no pain. Most importantly, in the present financial climate, it is cheap. PMID- 3103776 TI - Treatment of diabetes in pregnancy. PMID- 3103777 TI - Portraits from memory. 8--Lieutenant Colonel Frederick Murgatroyd RAMC (d 1951). PMID- 3103778 TI - Three cases of illness during a drug trial in healthy volunteers. PMID- 3103779 TI - Coroner overruled: time for reform? PMID- 3103780 TI - AIDS and intravenous drug use. PMID- 3103781 TI - Who may give blood? PMID- 3103782 TI - AIDS and life years lost: one district's challenge. PMID- 3103783 TI - HIV antibody testing. PMID- 3103784 TI - Dally, O'Donnell, and the GMC. PMID- 3103785 TI - Should we be screening for cervical cancer or breast cancer. PMID- 3103786 TI - Effects of breast conservation on psychological morbidity associated with diagnosis and treatment of early breast cancer. PMID- 3103787 TI - Prejudice against doctors and students from ethnic minorities. PMID- 3103788 TI - Adverse reaction monitoring using cohort identification. PMID- 3103790 TI - Potentially dangerous ampoule confusion. PMID- 3103789 TI - Cost of anaesthetic drugs and clinical budgeting. PMID- 3103791 TI - Adverse drug reactions checklist. PMID- 3103792 TI - Doppler studies in the growth retarded fetus. PMID- 3103793 TI - The use of monoclonal antibodies in the diagnosis of partially treated Pseudomonas aeruginosa meningitis: patient report. AB - The objective of this study was to evaluate the efficacy of mouse anti pseudomonas monoclonal antibodies to detect small numbers of pathogenic pseudomonas in the spinal fluid of a patient who had been treated with antibiotics for meningitis. Anti-605 monoclonal antibody against Pseudomonas aeruginosa PAC 605, a rough mutant, showed sensitivity similar to that of anti Fisher 1 monoclonal antibody in detecting P. aeruginosa Fisher 1 antigens in boiled spinal fluid drawn from a patient with a P. aeruginosa perispinal abscess and partially treated meningitis. PMID- 3103794 TI - Alterations of the blood coagulation system after accidental human inoculation by Bothrops jararaca venom. AB - Blood coagulation studies carried out on 78 patients up to 30 h after they were bitten by Bothrops jararaca snakes demonstrated clotting defects in 37 patients which included afibrinogenemia, reduced levels of prothrombin, of factors V and VIII, thrombocytopenia and activation of the fibrinolytic system. Factor IX and X levels were within normal range for all patients. These in vitro data suggest that the disseminated intravascular clotting observed in vivo following envenomation may be triggered by the intravascular release of patient thrombin by snake venom enzymes. PMID- 3103795 TI - Effect of nifedipine on the lower esophageal sphincter pressure in chagasic patients. AB - The effect of 10 mg of sublingual nifedipine on the lower esophageal sphincter pressure (LESP) was studied by continuous perfusion manometry in 15 Chagasic patients and 9 controls. Resting LESP was lower in Chagasic patients (13.51 +/- 2.37 mmHg) than in controls (19.60 +/- 2.51 mmHg, P less than 0.02). Nifedipine caused a gradual decrease in the LESP in both Chagasics and controls. Maximal reductions occurred 50 minutes after the drug administration when LESP was reduced to 60% of the resting LESP in the control group and to 43% in the Chagasic group. These results indicate that the striking abnormalities found in the intramural plexuses of the alimentary canal of Chagasic patients do not affect the responsiveness of LESP to nifedipine, and that nifedipine may be useful to reduce LESP in Chagasic megaesophagus. PMID- 3103796 TI - Adherent peritoneal mononuclear cells express chloroacetate esterases in vitro. AB - Murine peritoneal adherent mononuclear cells elicited by intraperitoneal glass implants express nonspecific esterases (alpha-naphthyl acetate esterases) as demonstrated by enzyme histochemical methods. After nine days of in vitro culture, 50% of cells obtained from normal mice and 100% of cells obtained from schistosome-infected mice expressed chloroacetate esterases (naphthol AS-D chloroacetate esterases). Fifty percent of the cells from normal mice continued to present nonspecific esterase activity, whereas cells from infected mice presented only chloroacetate esterase activity. This modulation of esterase expression can be interpreted to be a reflection of in vitro cell differentiation. PMID- 3103797 TI - Third parties in the midst of everyone's expectations. PMID- 3103798 TI - The doctor, the patient and the third party payer: three begins to be a crowd. PMID- 3103799 TI - Paying the piper: what tune will the government call? PMID- 3103800 TI - Health care's third party payer: interloper or facilitator? PMID- 3103801 TI - The deficit: America's problem--medicine's challenge. PMID- 3103802 TI - Private utilization review and quality assurance. PMID- 3103803 TI - Epidemiologic study of Chagas' disease in a town in Oaxaca, Mexico. PMID- 3103804 TI - Establishment of baseline data on the insecticide susceptibilities of the Chagas' disease vector Rhodnius prolixus in Venezuela. PMID- 3103805 TI - N-propargylbenzylamine, a major metabolite of pargyline, is a potent inhibitor of monoamine oxidase type B in rats in vivo: a comparison with deprenyl. AB - In an effort to explore the contribution of the metabolites of pargyline towards the in vivo inhibition of monoamine oxidase (MAO), the effects of pargyline and its major metabolites on the production and metabolism of a number of biogenic amines were studied in rats. The administration of pargyline gave rise to three major ethyl acetate extractable metabolites: benzylamine, N-methylbenzylamine and N-propargylbenzylamine (NPB). Only NPB demonstrated in vivo monoamine oxidase inhibitory properties at an acute dose of 30 mg kg-1. The acute effects of pargyline, NPB, and deprenyl on urine and brain concentrations of a number of biogenic amines (phenylethylamine (PEA), m- and p-tyramine, noradrenaline (NA), dopamine, and 5-hydroxytryptamine (5-HT) and their metabolites were evaluated. Increased urine and brain concentrations of PEA were considered to represent in vivo inhibition of type B MAO while decreased concentrations of NA and 5-HT metabolites were regarded as indicators of an in vivo inhibition of MAO type A. NPB, like deprenyl and pargyline, significantly increased urine and brain PEA while only pargyline reduced 5-HT metabolism, suggesting that the metabolism of pargyline to NPB may contribute towards the MAO type B inhibitory effects of pargyline in vivo. Since the therapeutic benefits of MAO inhibitors in clinical practice usually require some period of chronic treatment, the chronic effects of repeated 14 daily doses of the above MAO inhibitors on central and peripheral biogenic amines were evaluated at the following times: during treatment, one day and five days after termination of treatment. The biochemical changes observed during the course of chronic NPB, pargyline and deprenyl treatments generally follow the expected in vitro characteristics of these drugs, but the detailed changes observed suggest clear differences. For example, the in vivo effect of pargyline on urine 5-hydroxyindoleacetic acid excretion was considerably weaker than its effect on the excretion of NA and dopamine metabolites. These changes are opposite to the in vitro effects of pargyline on 5-HT, dopamine and NA oxidative deamination. Inhibitions of the metabolism of all the amines studied were clearly observed during chronic MAOI treatments, but these effects were less evident five days after the end of treatment, suggesting an almost normal metabolism of biogenic amines. It is concluded that while MAO inhibitors may be the primary compound responsible for MAO inhibition, the effects of their metabolites in some cases may also play equally important roles in the regulation of monoamines both in the periphery and the brain. Thus, as demonstrated here, NPB was found to be as potent as pargyline and deprenyl with regard to its in vivo MAO type B inhibitory properties. PMID- 3103807 TI - Increased intestinal permeability in patients with rheumatoid arthritis: a side effect of oral nonsteroidal anti-inflammatory drug therapy? AB - Intestinal permeability in controls and in patients with active rheumatoid arthritis was assessed by measuring the radioactivity in 24-h urine collections after oral administration of 51Cr-EDTA. Intestinal permeability in the patients was found to be significantly increased in comparison to controls. Of the patients, 6/7 (86%) not taking any prescribed nonsteroidal anti-inflammatory drug (NSAID) at the time of study had normal results, whereas 23/29 patients (79%) taking prescribed NSAIDs displayed increased intestinal permeability. It has not been determined beyond doubt whether this finding is due to disease process or therapy with oral NSAIDs. PMID- 3103806 TI - The adenosine receptor-mediated inhibition of noradrenaline release possibly involves an N-protein and is increased by alpha 2-autoreceptor blockade. AB - The stimulation-evoked overflow of [3H]-noradrenaline from slices of the rabbit hippocampus is inhibited by alpha 2-autoreceptors as well as by adenosine (A1) receptors. Slices of rabbit hippocampus were labelled with [3H]-noradrenaline, superfused continuously and stimulated twice electrically (rectangular pulses; 2 ms, 3 Hz, 24 mA, 5 V cm-1). Treatment of hippocampal slices with N-ethylmaleimide (NEM, 30 microM; 30 min), which functionally disturbs certain N-proteins, decreased the inhibitory action of adenosine receptor agonists like (-)-N6-(R phenylisopropyl)-adenosine ((-)-PIA) and adenosine on noradrenaline release. Release inhibition caused by (-)-PIA (0.03-1 microM) was antagonized by NEM in a non-competitive manner in the absence and in the presence of the alpha 2 adrenoceptor antagonist yohimbine. The adenosine receptor antagonist 8 phenyltheophylline significantly increased the evoked noradrenaline release by about 15% in control slices by diminishing the inhibitory action of endogenous adenosine. In NEM-treated slices this effect of 8-phenyltheophylline was not seen. In the presence of (-)-PIA (0.1 microM), i.e. under conditions of an increased inhibitory tone, release facilitation by 8-phenyltheophylline was decreased by NEM compared to that in the respective controls. Occupation of the A1-receptor with (-)-PIA prior to and during the NEM treatment did not protect the A1-receptor-coupled signal transduction system from being affected by NEM. In the presence of the alpha 2-adrenoceptor antagonist yohimbine, the inhibitory action of (-)-PIA was strongly increased. The above results suggest the involvement of a regulatory N-protein in the A1-receptor-mediated inhibition of noradrenaline release and an interaction between the alpha 2-autoreceptor and the A1-receptor-coupled signal transduction system, possibly at the level of a N protein. PMID- 3103808 TI - 7S IgM in the sera of patients with arthritis. AB - Using radial immunodiffusion in 7% agarose, 7S IgM was quantified in the sera of 45 normal individuals, 37 patients with rheumatoid arthritis (RA), 18 patients with psoriatic arthritis and 11 patients with ankylosing spondylitis. 7S IgM was only found in the sera of patients with RA, 43% of whom had detectable levels of 7S IgM (median 47.5 micrograms/ml). The patients with 7S IgM had significantly higher IgM rheumatoid factor (IgM RF) and C-reactive protein levels in their sera (p less than 0.005). There was a strong correlation between 7S IgM and IgM RF levels in the sera of these patients. These data demonstrate that patients with more active and severe disease have 7S IgM present in their sera but the absence of 7S IgM from the sera of some patients with high levels of IgM RF and CRP suggest that additional factors may influence the synthesis and secretion of 7S IgM by B cells in RA. PMID- 3103809 TI - IgG (kappa) paraproteinaemia and arthritis. AB - Three patients with IgG (kappa) paraproteinaemia in association with inflammatory polyarthritis are described. Two of the patients had an erosive deforming arthritis, and the third had a non-erosive arthritis and necrotizing vasculitis. Possible aetiological relationships between the paraproteinaemia, arthritis and vasculitis are discussed. PMID- 3103810 TI - Bilharziasis in malignant tumours of the urinary bladder. AB - In a review of 2248 cystoscopic examinations conducted over 10 years, malignant tumours of the urinary bladder were found in 172 patients. In 128 of these the condition was associated with bilharziasis. The lateral wall of the bladder was the commonest site (52.3%). Squamous cell carcinoma occurred in 78.1%. Forty-nine patients refused surgery and eight were found to have advanced inoperable tumours. Seventy-one patients had a total cystectomy. There were no operative deaths but post-operative complications occurred in nine cases. Eight patients died within 2 years but 21 were well and tumour-free at 5 years. It was concluded that there is a marked association between bilharziasis and bladder cancer. When the tumour is operable, cystectomy is the treatment of choice. PMID- 3103811 TI - Priapism in patients treated with total parenteral nutrition. AB - Three patients who developed priapism associated with total parenteral nutrition are reported. To reduce the risk of priapism in such patients it is suggested that fat emulsions stronger than 10% should not be administered. PMID- 3103812 TI - Giant bladder diverticulum: an unusual presentation. PMID- 3103813 TI - Orthotopic liver transplantation: postoperative complications and their management. AB - The Birmingham liver transplant programme started in 1982. Forty-six patients have been transplanted with a follow-up of 3 months or longer. Twenty-seven patients are still alive, of whom sixteen have lived for more than one year. The 30 day hospital mortality was 30.4 per cent and the actuarial predicted one year survival 55.5 per cent. Four patients have been regrafted for chronic rejection and graft failure. Thirteen patients have required surgery in the postoperative period for: bleeding (two), removal of abdominal packs (four), biliary leaks and obstruction (five), duodenal perforation (one) and small bowel obstruction (one). Acute rejection was common, occurring in 30 patients and progressing to chronic rejection in 4. Ten patients developed renal failure with an 80 per cent mortality and eleven patients developed grand mal fits. Severe bleeding (greater than 70 units) was associated with previous abdominal surgery and a high mortality (88.9 per cent). Opportunistic fungal infection carried a 100 per cent mortality. Although more than half of all transplanted patients will survive for more than one year, the postoperative period is still one of high morbidity and mortality. PMID- 3103814 TI - New evidence on childhood leukaemia and nuclear establishments. PMID- 3103815 TI - Chlormethiazole and alcohol: a lethal cocktail. PMID- 3103816 TI - Stopping bleeding by embolisation. PMID- 3103817 TI - The aetiology of preterm labour. PMID- 3103818 TI - An uncompromising report on health visiting for the elderly. PMID- 3103819 TI - Childhood leukaemia in the West Berkshire and Basingstoke and North Hampshire District Health Authorities in relation to nuclear establishments in the vicinity. AB - During the years 1972-85, 89 children aged 0-14 were registered with leukaemia in the West Berkshire and Basingstoke and North Hampshire District Health Authorities. Two nuclear establishments are located within the health authorities, and a third is situated nearby. Fifty of the 143 electoral wards in the two district health authorities lie wholly within, or have at least half their area lying within, a circle of radius 10 km around the establishments. In those 50 electoral wards 41 children aged 0-14 were registered with leukaemia, 28.6 registrations being expected on the basis of leukaemia registration rates in England and Wales (incidence ratio = 1.4, p less than 0.05). This excess was confined to children aged 0-4, among whom there were 29 registrations of leukaemia, 14.4 being expected (incidence ratio = 2.0, p less than 0.001). In the remaining 93 electoral wards there was a small and non-significant increase in the number of registrations of leukaemia at age 0-14 (48 observed, 40.8 expected; incidence ratio = 1.2). There was no obvious trend in the incidence of childhood leukaemia over the 14 years and the overall occurrence of the malignancy in the 143 electoral wards was consistent with a random distribution. In the surrounding Oxford and Wessex Regional Health Authorities the number of registrations of leukaemia at age 0-14 was virtually identical with that expected on the basis of registration rates in England and Wales (362 observed, 372.5 expected; incidence ratio = 1.0). These data indicate that in the two district health authorities studied there was an excess incidence of childhood leukaemia during 1972-85 in the vicinity of the nuclear establishments. In the West Berkshire and Basingstoke and North Hampshire District Health Authorities an average of 60,000 children aged 0-14 lived within a 10 km radius of a nuclear establishment each year. The normal expectation of leukaemia in these children was two cases a year, whereas the recorded incidence was three cases per year, representing one extra case of leukaemia each year among these 60,000 children. PMID- 3103820 TI - Fallout, radiation doses near Dounreay, and childhood leukaemia. AB - Possible explanations for the recently reported increased incidence of childhood leukaemia around Dounreay were examined in the light of changes in the national incidence of leukaemia that occurred during the period of exposure to fallout from international testing of nuclear weapons in the atmosphere. It was concluded that the increase could not be accounted for by an underestimate of the risk of leukaemia per unit dose of radiation at low doses and low dose rates, nor by an underestimate of the relative biological efficiency of high as compared with low linear energy transfer radiation. One possible explanation was underestimation of doses to the red bone marrow due to the discharges at Dounreay relative to the dose from fallout, though investigation of ways in which this might have occurred did not suggest anything definite. Other possible explanations included a misconception of the site of origin of childhood leukaemia, outbreaks of an infectious disease, and exposure to some other, unidentified environmental agent. These findings weigh heavily against the hypothesis that the recent increase in childhood leukaemia near Dounreay might be accounted for by radioactive discharges from nuclear plants, unless the doses to the stem cells from which childhood leukaemia originates have been grossly underestimated. PMID- 3103821 TI - Acute polyradiculoneuropathy after amitriptyline overdose. PMID- 3103822 TI - Social future of elderly admitted to acute care hospital: opinion of patient or family as predictive factor of subsequent transfer to long term care. PMID- 3103823 TI - Recent trends in mortality from and incidence of myocardial infarction in Stockholm. PMID- 3103824 TI - HIV infection and AIDS in newborn babies of mothers positive for HIV antibody. PMID- 3103825 TI - Fall in intraocular pressure during acute hypoglycaemia in patients with insulin dependent diabetes. PMID- 3103826 TI - Survival after burial in an avalanche. PMID- 3103827 TI - Gynaecomastia induced by phenytoin in men with epilepsy. PMID- 3103828 TI - Severe cholestasis associated with stanozolol. PMID- 3103829 TI - Guillain-Barre syndrome after myocardial infarction. PMID- 3103830 TI - Long term exposure to hydrogen sulphide producing subacute encephalopathy in a child. PMID- 3103831 TI - Antibodies to Campylobacter pyloridis in household contacts of infected patients. PMID- 3103832 TI - Erythrocytosis induced by danazol in an anephric patient. PMID- 3103833 TI - Assault on a GP. PMID- 3103834 TI - Determinants of mood in general practitioners. AB - A pilot study was conducted in which 44 general practitioners completed cognitive behavioural self monitoring diaries. Hourly changes in emotional state were recorded together with associated circumstances. Lowering of mood was associated mainly with "hassle" at work, pressure of time, and domestic dissatisfaction. Improvement in mood was associated with domestic happiness and satisfaction at working efficiently and to time. Mood was significantly lower when the doctor was on call. Women doctors were more prone to mood changes associated with domestic matters. Responses to a questionnaire suggested that the doctors preferred traditional clinical medicine to problems of a social or psychological origin. Managerial skills would help alleviate several of the problems identified in this study and should be more prominent in the training that all doctors receive. PMID- 3103835 TI - Tennis elbow: conservative, surgical, and manipulative treatment. PMID- 3103836 TI - Portraits from memory. 9--Professor Matthew J Stewart (1885-1956). PMID- 3103837 TI - Community care for the elderly 1976-84. AB - The aging of the elderly population is of crucial importance as people who are over 80 make far greater use of health and social services than any other age group. Government guidelines on the provision of services, which are generally related to the whole population aged 65 and over, fail to take account of this change in the age structure of the elderly population and are no longer appropriate. Recent trends in the provision of domiciliary services, day care, specialist housing for the elderly, and residential care have been related to changes in the number of potential consumers. Ironically, despite the government's stated commitment to "community care," the chief growth area has been private institutional care. The number of day care places and sheltered housing units has also increased in real terms, but the provision of domiciliary services, such as home help and health visitor visits to the elderly, has either fallen behind or barely matched the increase in the number of very old people. If community care is to be made a reality and if the present inadequate levels of service are to be maintained, let alone improved, then additional resources, greater cooperation among agencies, and a more imaginative approach to the development and delivery of services are urgently needed. PMID- 3103838 TI - Misdiagnosis of diabetic ketoacidosis as hyperventilation syndrome. PMID- 3103839 TI - Father fails in attempt to stop girlfriend's abortion. PMID- 3103840 TI - ABC of 1 to 7 (revised). Child abuse. PMID- 3103841 TI - Decapitation of academic chemical pathology. PMID- 3103842 TI - Future of the pathologist in an era of technological change and cost containment. PMID- 3103843 TI - Head injuries in the elderly. PMID- 3103844 TI - Snoring as a risk factor for ischaemic heart disease and stroke in men. PMID- 3103845 TI - Christ Church conference on postgraduate education--25 years on. PMID- 3103846 TI - Doppler studies in the growth retarded fetus. PMID- 3103847 TI - Dialysis arthropathy: amyloid or iron? PMID- 3103848 TI - Poverty and teenage pregnancy. PMID- 3103849 TI - Depression and outcome in acute myocardial infarction. PMID- 3103850 TI - Asthma mortality: comparison between New Zealand and England. PMID- 3103852 TI - Waiting time for urgent appointments. PMID- 3103851 TI - Chronic renal failure associated with topical application of paraphenylenediamine. PMID- 3103853 TI - AIDS: a doctors duty. PMID- 3103854 TI - Thyroid disease in pregnancy. PMID- 3103855 TI - Why doctors must grapple with health economics. PMID- 3103856 TI - Cloning and developmental expression of the murine neurofilament gene family. AB - DNA clones encoding the 3 mouse neurofilament (NF) genes have been isolated by cross-hybridization with a previously described NF-L cDNA probe from the rat. Screening of a lambda gt10 cDNA library prepared from mouse brain RNA led to the cloning of an NF-L cDNA of 2.0 kb that spans the entire coding region of 541 amino acids and of an NF-M cDNA that covers 219 amino acids from the internal alpha-helical region and the carboxy-terminal domains of the protein. These cDNA clones were used as probes to screen mouse genomic libraries, and cosmid clones containing both NF-L and NF-M sequences were isolated as well as overlapping cosmids containing the NF-H gene. This strongly suggests that the 3 neurofilament genes are organised in a cluster and derived by gene duplication of a common ancestral gene. RNA blot analyses using specific DNA probes for each of the genes indicate that NF mRNAs are differentially expressed during brain development. The NF-L and NF-M mRNAs are detected early in the embryonal brain, with a progressive increase in their levels during development, while the NF-H mRNA is barely detectable at embryonal stages and accumulates later in the postnatal brain. PMID- 3103857 TI - Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2. AB - We have previously identified a partial human cDNA for MAP2, and we now report the isolation of human cDNA clones for tau. The RNA species recognized by the tau clones is a 6 kilobase (kb) message that is expressed in the human brain but not in other human tissues, and exhibits a developmental shift in size. We also report the human chromosomal localization of the MAP2 and tau genes. The MAP2 cDNA pKN7 was used to localize the MAP2 gene to chromosome 2q34-35. The tau cDNAs were used to confirm the presence of a tau gene on chromosome 17q21 and an additional region of homology on chromosome 6p21. PMID- 3103858 TI - 5-Hydroxytryptamine is synthesized in neurons terminating in the neural and intermediate lobes of the rat pituitary gland. AB - Immunocytochemistry has revealed that nerve fibers within the neural and intermediate lobes of the rat pituitary gland contain 5-hydroxytryptamine (5-HT). Recent anatomical evidence suggests that the content of this amine in the intermediate but not the neural lobe of the pituitary gland may represent 5-HT that has been taken up from the blood rather than synthesized intraneuronally. The purpose of this study was to determine if 5-HT is synthesized in neurons of the neurointermediate lobe of the pituitary gland. 5-HT synthesis was estimated by measuring the accumulation of the 5-HT precursor, 5-hydroxytryptophan (5-HTP), in the neurointermediate lobe of male Long-Evans rats following the administration of NSD 1015, an inhibitor of aromatic L-amino acid decarboxylase. Thirty min following the injection of NSD 1015 (100 mg/kg, i.p.), 5-HTP accumulated in the neurointermediate lobe and the rate of this accumulation was increased by the administration of the 5-HTP precursor, tryptophan, and by electrical stimulation of the pituitary stalk. In addition, repeated injections of the 5-HT uptake inhibitor, fluoxetine (10 mg/kg, i.p., every 12 h for a total of 7 injections), induced a marked depletion of platelet 5-HT but did not alter the concentration of 5-HT in either the neural or intermediate lobes of the pituitary gland. Taken together these results indicate that much of the 5-HT in the neurointermediate lobe of the pituitary gland does not represent 5-HT taken up from the blood, but rather the amine is synthesized in neurons projecting to this region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103859 TI - TRH axon terminals in synapsis with GRF neurons in the arcuate nucleus of the rat hypothalamus as revealed by double labeling immunocytochemistry. AB - Synaptic input to neurons containing growth hormone-releasing factor (GRF) by axon terminals containing thyrotropin-releasing hormone (TRH) in the arcuate nucleus (AN) of the rat hypothalamus was examined using a method combining pre embedding peroxidase-anti-peroxidase for GRF with postembedding immunocolloidal gold staining for TRH. The TRH-like immunoreactive axon terminals were found to make synaptic contact with GRF-like immunoreactive neurons with unlabeled axon terminals. From these findings, TRH-containing neurons in the hypothalamic AN of the rat may be considered to innervate GRF neurons, to regulate GRF secretion or to have some other functions via synapses. PMID- 3103860 TI - Periventricular noradrenergic systems are critical for angiotensin-induced drinking and blood pressure responses. AB - Deficits in experimentally induced drinking and pressor responses after administration of 6-hydroxydopamine (6-OHDA) into the lateral cerebral ventricle (LCV) have been reported. Questions have arisen, however, as to whether these effects are due to non-specific actions of the neurotoxin and, if specific, whether the depletion of dopamine (DA) or of norepinephrine (NE) is the critical factor for producing the impairments. In the present report methods to deplete brain catecholamine (CA) differentially were employed in order to test the hypothesis that central 6-OHDA injections act on brain CA substrates per se to produce behavioral and physiological response deficits to angiotensin II (ANG II) challenges. The findings support the interpretation that forebrain dopamine is essential for the mediation of sensorimotor integration involved in response to acute homeostatic stressors. In addition, the outcome identifies an important role for forebrain noradrenergic systems in the mediation of ANG II-elicited drinking and blood pressure responses. PMID- 3103861 TI - Effects of neonatal 6-hydroxydopamine treatment upon morphological organization of the posteromedial barrel subfield in mouse somatosensory cortex. AB - While recent studies indicate that proposed regulation of visual cortex plasticity by norepinephrine (NE) probably involves 6-hydroxydopamine (6-OHDA) effects other than NE depletion, reports of diminished neuronal maturation and reduced postweaning sensitivity to environmental conditions in animals treated with anti-adrenergic compounds continue to suggest a role for NE in neocortical development. To assess its possible role in development of a highly organized neocortical structure, the effects of postnatal 6-OHDA administration upon development of the somatosensory cortical posteromedial barrel subfield (PMBSF), which subserves the large facial whiskers, were observed in mice with whiskers in the middle row of the face removed unilaterally. Treatment with 6-OHDA caused 96 98% depletion of NE in parietal cortex. There were no effects of (or lesion interactions with) 6-OHDA treatment on barrel size in measures of Nissl-stained neurons, and 6-OHDA effects on numerical measures of dendritic branching of Golgi impregnated non-pyramidal neurons in PMBSF were negligible. There were, however, effects of 6-OHDA treatment upon the highly ordered arrangement of dendrites within barrels. In 6-OHDA-treated animals, the class I (spiny and sparsely spined) cell dendrites were less attracted to the barrel hollow. In controls, for class I cells with their somata within the barrel wall, there was a high correlation between the distance from the soma to the hollow and the amount of dendrite in the wall, reflecting the distance the dendrite traverses to the hollow. In 6-OHDA-treated animals, this correlation was absent, i.e., cells at any distance from the hollow tended to have a high percentage of dendrite in the wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103862 TI - Serum effects on substrate oxidation by dissociated brain cells: possible sites of action. AB - This report is an extension of recent studies indicating the presence of a factor in serum that preferentially inhibits 14CO2 production from labeled glucose. Experiments with dissociated cells revealed that the inhibitory effects of serum were only slightly changed over more than a 50-fold range in initial glucose concentration. Serum had no effect on the rate of glucose transport (uptake of 1,3[3H]2-deoxyglucose). The inhibitory effect of serum was greater on 14CO2 production from [6-14C]glucose than [1-14C]glucose. Other studies revealed that 14CO2 production from [1-14C]pyruvate was more than 5 times the rate obtained using [3-14C]pyruvate; however, the inhibitory effect of serum was much greater on the latter (20% vs 60% inhibition respectively) at 2 mM pyruvate and in the presence of 1% fetal bovine serum. Attempts to characterize the factor using Amicon filtration showed the highest inhibitory activity in a 10,000 mol. wt. fraction, although some inhibitory activity was found in commercial preparations of bovine serum albumin. Delipidation of serum had no effect. Based on these results, we postulate that the observed decrease in labeled CO2 production reflects the regulation of substrate utilization at the pyruvate carboxylase step by one or more factors in serum (with a mol. wt. of approximately 10,000). PMID- 3103863 TI - Further studies on the neurochemical specificity of 6-hydroxydopamine as compared to radiofrequency lesions. AB - Despite the large volume of literature during the past 15 years addressing the problem concerning the neurochemical specificity of 6-hydroxydopamine (6-OHDA), there is still disagreement over this issue. While some claim that the catecholamine-specific effects of this drug can be maximized by controlling the dose injected, others claim that all doses of 6-OHDA produce non-specific damage (NSD), thereby contraindicating its use in experimental paradigms. In the present study, we examined the degree of neurochemical specificity of 6-OHDA by comparing the volume of proximal accumulation to that of NSD, produced by 6-OHDA (2 microliter of 8 micrograms/microliter) or radiofrequency (RF) lesions (60 degrees C for 50 s and 45 degrees C for 30 s), placed in the medial forebrain bundle. The volume of NSD and accumulation produced by 6-OHDA was significantly less than that produced by large RF lesions which had a similar effect on the gross behaviour of albino rats. Smaller RF lesions produced similar volumes of NSD but less amine accumulation than did 6-OHDA, and did so without affecting normal behaviour. The ratio of NSD to accumulation in 6-OHDA treated rats was 3/1, while large and small RF lesions produced a NSD/accumulation ratio of 15/1. The present study introduces a novel method of determining the degree of neurochemical specificity which can be achieved with 6-OHDA and reveals that it is several magnitudes more neurochemically specific than RF lesions. PMID- 3103864 TI - A new heterotopic callosal projection of primary visual cortex in the monkey, Callithrix jacchus. AB - A callosal projection of area 17 upon the dorsomedial visual area in the marmoset monkey was demonstrated by means of retrograde transport of neuronal tracers. The projection was restricted to those regions representing the vertical meridian in the two areas. This finding, and the data of other authors, indicate that the monkey area 17 projects transcallosally onto homotopic and several heterotopic targets. PMID- 3103865 TI - Bacterial peptidoglycans as modulators of sleep. I. Anhydro forms of muramyl peptides enhance somnogenic potency. AB - Chemically defined muramyl peptides (MPs), derived primarily from enzymatic digests of Neisseria gonorrhoeae peptidoglycan, were used to define the structural determinants of MP-mediated somnogenic activity. One of these, i.e. N acetylglucosaminyl-N-acetyl-1,6-anhydro-N-acetylmuramyl-alanyl-glutamy l- diaminopimelyl-alanine, was structurally identical to the major naturally occurring MP previously detected in mammalian brain and urine. The somnogenic potency of this MP was similar to that of the corresponding disaccharide pentapeptide containing an additional alanine at the C-terminus and the analogous anhydro-muramic acid-containing monosaccharide tetrapeptide lacking the glucosamine moiety. Infusion of as little as 1 pmol of these highly active MPs increased significantly the percentage of slow-wave sleep in experimental animals. In fact, each of 5 anhydro-muramyl disaccharide peptides tested was somnogenic at a dose of 10 pmol or less and, as far as tested, the activity was affected only slightly by the length or composition of the peptide side chain. However, none of a matched set of analogous MPs, differing only in replacement of the anhydro-muramyl end by a hydrated muramic acid residue, was somnogenic at this dose. A modified form of the hydrated muramyl tripeptide containing a free amide on the diaminopimelic acid residue was completely inactive in amounts up to 1000 pmol. Together, the current data suggested: that the anhydro-muramic acid end (but not the glucosamine moiety) is essential for maximal somnogenic potency; and that amidation of carboxyl groups on the peptide-side chain may block MP mediated somnogenic activity. PMID- 3103866 TI - Bacterial peptidoglycans as modulators of sleep. II. Effects of muramyl peptides on the structure of rabbit sleep. AB - Sleep-promoting substances derived from human urine and rabbit brain were identified as muramyl peptides (MPs). We report in the accompanying paper that in the molecular structure of MPs, the 1,6-anhydro muramic acid moiety of MPs is important for enhancement of slow-wave sleep (SWS) in rabbits. Here, we document more extensively the effects of one MP: 1,6-anhydro-muramyl-alanyl-glutamyl diaminopimelyl-alanine (AMTP for anhydro-muramyl tetrapeptide) on sleep structure of rabbits. AMTP significantly increased percent of time spent in SWS but its effects on rapid eye movement (REM) sleep were dose-dependent. Brain temperatures were significantly elevated but continued to fluctuate with sleep and wake state transitions indistinguishably from control. Sleep was episodic and animals could be easily aroused. AMTP increased number of SWS episodes and decreased number of REM episodes. There was a shift in the distribution of sleep-wake episode durations: longer waking and REM episodes were decreased, thus increased the proportion of shorter episodes. Increased duration of SWS resulted from a larger number of SWS episodes longer than 8 min. We conclude that AMTP amplifies the SWS compenent of physiological sleep. PMID- 3103867 TI - Hirano bodies contain tau protein. AB - Hirano bodies are intraneuronal inclusions whose frequency increases with age and Alzheimer's disease. These paracrystalline inclusions have been shown previously using immunocytochemistry to share epitopes with actin, tropomyosin, alpha actinin and vinculin. Hirano bodies have not previously been demonstrated to share components with neurofibrillary tangles, another intraneuronal inclusion characteristic of Alzheimer's disease. In this study, we show that Hirano bodies bind antibodies to the microtubule-associated protein tau, a component of Alzheimer neurofibrillary tangles. PMID- 3103868 TI - Carbonic anhydrase activity develops postnatally in the rat optic nerve. AB - We examined the appearance of carbonic anhydrase (CA) activity in rat optic nerves (RONs) 5-77 postnatal days of age and correlated the appearance of enzyme activity with structural and physiological alterations. CA activity was nearly absent before 10 days of age and appeared in this CNS white matter tract with a developmental time-course similar to that of oligodendrogliogenesis and myelinogenesis. When oligodendrocytes and myelin were depleted in the RON by treatment with a mitotic inhibitor, CA activity was markedly reduced. These observations support the hypothesis that CA is contained primarily in oligodendrocytes and myelin. Neural activity in the RON caused changes in extracellular pH (pHo) and the character of these pHo responses was very age dependent; older nerves exhibited much larger acid shifts than neonatal nerves. The development of CA activity may be a factor contributing to this physiological alteration. PMID- 3103869 TI - Lesions of the sexually dimorphic nucleus of the preoptic area: effects upon LH, FSH and prolactin in rats. AB - Bilateral lesions were placed in the sexually dimorphic nucleus of the preoptic area (SDN-POA) in castrated adult male rats in an attempt to determine a physiologic role for this nucleus. These lesions significantly attenuated the increase in plasma FSH and LH due to simultaneous castration at 24 hr, and at 7 and 14 days following surgery, and significantly decreased the levels of plasma prolactin on comparison with pre-operative values and those of castrated controls. When rats were castrated and lesions placed at 14 days following castration, plasma levels of FSH, LH and prolactin were significantly decreased at 24 hr and at 7 days following surgery. Lesions which were placed lateral or caudal to the SDN-POA simulated the effects of lesions placed within the SDN-POA upon plasma LH, FSH and prolactin, with lateral lesions being most effective. However, lesions which were placed dorsal or rostral to the SDN-POA had no effect. The results of these studies suggest that the SDN-POA may be involved in the regulation of LH, FSH, and prolactin release. PMID- 3103870 TI - A microcomputer aided control system for visual tracking task of monkey. AB - A microcomputer aided control system for visual tracking tasks is described. A video monitor displays positions of target and pointer. In a handle task, the horizontal position of a pointer is coupled to the angular position of a manipulandum. The task involves alignment and maintenance of a pointer on the target. In a bar press task, the pointer moves incrementally after each preset number of bar presses. A microcomputer and video monitor afford system flexibility, while a panel of manual switches permits the setting up of a variety of experimental conditions without extensive keyboard inputs and has the added advantage of constant display of task details. The program is written in assembly language to meet requirements for program control speed and allow timing measurement in msec. This system may be useful in the behavioral study of physiological and neurophysiological functions. PMID- 3103871 TI - [Surgery for congenital malformations: from ethics to economics]. PMID- 3103872 TI - Early oral feeding of patients with extensive burns. AB - The oral administration of fluid to patients with extensive burns is usually acceptable during the first 48 h post-burn. Nutrients can be added to the drinks, whereby a hyperalimentation regimen can be reached within a few days. However, accurate monitoring through laboratory investigations needs to be carried out during this treatment. PMID- 3103873 TI - Enhanced lymphocyte response to PHA among leukemia patients taking oral lithium carbonate. AB - Seven children receiving maintenance therapy for acute lymphoblastic leukemia (in remission) were given oral lithium carbonate for 12 weeks. Hematologic values, serum immunoglobulin levels, and responsiveness of peripheral blood mononuclear cells to mitogen stimulation were studied during the lithium treatment period, and compared to measurements made during a 12-week period when no lithium was administered (children served as their own controls). Changes attributable to treatment with lithium carbonate included increases in total white blood cell count, circulating neutrophil count, and response to phytohemagglutinin-P. No important toxicity to lithium carbonate was observed. PMID- 3103874 TI - [Infection of the athymic rat by Toxoplasma gondii]. AB - In contrast to normal rats which are resistant to T. gondii infection (10(7) tachyzoites), athymic rats did not survive an intraperitoneal infection with 10(3) toxoplasma. When nude rats were injected intravenously with lymph node cells from hirsute littermates, they became resistant in a dose-dependent manner to the infection. In addition, reconstituted athymic rats having survived for more than 4 months the first infection were also protected against a second challenge with 10(5) tachyzoites. Anti-T. gondii antibody levels detected in reconstituted athymic rats were related to protection. These preliminary findings suggest that T-dependent immunity is essential in the development of effector mechanisms involving antibodies in resistance to toxoplasmosis. PMID- 3103875 TI - [Demonstration of an oxidative biotransformation of 9-methoxyellipticine. Comparison with the case of 9-hydroxyellipticine]. AB - Evidences for the formation of the glutathione-hydroxyellipticine adduct during the rat metabolism of 9-methoxyellipticine are provided. These data suggest that such a cytotoxic molecule might behave as a pro-alkylating agent in vivo. PMID- 3103876 TI - [A specific marker of thrombolysis: DDE complex]. AB - A specific determination of fibrin degradation product (FbDP) is essential for the monitoring of thrombolytic therapy. In patients under thrombolytic therapy, even with tpA (tissue type plasminogen activator) fibrinogen is degraded, and fragment D derived from fibrinogen degradation, is evidenced in the plasma of treated patients. In order to determine specifically the FbDP, even in the presence of fragment D, we take into account the fact that FbDP are complexes such as DDE complex. Therefore a new Elisa technique is proposed. FbDP and fragment D are captured from plasma by immobilized anti D neo monoclonal antibody which recognizes an epitope accessible on fragment D but does not react with undegraded fibrinogen. DDE complexes are then detected specifically using a peroxidase-labelled anti E antibody. The advantage of this technique is discussed in this paper. PMID- 3103877 TI - [Immunocytochemical demonstrating of a neurofibrillary component of the peripheral nervous system manifested by a human natural antibody]. AB - Human serum SH2172, obtained from a girl suffering from bullous dermatosis, showed a natural immunoreactivity against the peripheral nervous system (PNS) of rat, mouse and hamster. Immunocytochemical staining and examination by light and electron microscopy demonstrated an intracellular neurofibrillary network localized in neurites and neuronal pericaryons. Comparative testing clearly showed that SH2172 immunoreactivity is different from that of the antibodies against the triplet of proteins NFP70, 160 and 200 kD. This unique serum should be a useful probe to study PNS neurocytoskeleton. PMID- 3103878 TI - [A new intracellular protozoon of Salmo gairdneri Richardson, 1836 (teleost fish). Taxonomic affinities]. AB - Macrophages of 1+ rainbow trout are parasitised by an unknown protozoan. An ultrastructural study permits to associate it with the genus Dermocystidium described in many fishes. This protozoan is characterized by a large vacuole of mitochondrial origin and by concentric structured bodies. PMID- 3103879 TI - [Effect of exogenous gangliosides on the metabolism of inositol compounds in chick neurons in primary culture]. AB - A mixture of exogenous gangliosides at 10(-8) M and 10(-5) M concentration added to the medium of chick neurons stimulates the metabolism of inositol compounds. Notably the incorporation of [3H] myo-inositol is increased in phosphatidylinositol and in inositol triphosphate. Gangliosides, hence, by increasing the production of second messengers might regulate the phosphorylation processes of neuronal proteins. PMID- 3103880 TI - [Therapeutic trials of experimental murine malaria with the quassinoid, glaucarubinone]. AB - Prevention and treatment of malaria are endangered by the appearance of chemoresistance against the common anti-malarial drugs by Plasmodium falciparum. Today, only a quinoline derivative, mefloquine, is a safe and effective agent against P. falciparum. An in vitro antiplasmodial activity having been found for the quassinoid glaucarubinone we tested its in vivo therapeutic action on mice infected with a P. berghei strain. At low doses, glaucarubinone retarded mortality by exerting a partial, temporary, inhibition of parasitaemia; its toxicity, however, precludes, further applications at the present time. PMID- 3103881 TI - [Cutaneous changes induced by a dose of DEC in rodents with skin microfilaria: relevance of these phenomena for understanding the Mazzotti reaction and the pathogenesis of human onchocerciasis]. AB - A single dose of DEC was given to Lemniscomys striatus parasitized by Monanema martini. The histopathological analysis of ear-lobe skin sections shows: a massive escape of microfilariae from the lymph capillaries, a major vascular exudative reaction with edema and diapedesis of blood cells. This inflammatory process leads to the destruction of the extralymphatic microfilariae and it induces a subacute and chronic dermatitis at the 7th day. These findings explain the pathogenesis of Mazzotti reaction during treatment of human onchocerciasis. The use of DEC produces precisely the factor that is responsible for the severity of the human disease: inflammatory reactions around the extralymphatic microfilariae. PMID- 3103882 TI - [Functional reinnervation of skeletal muscle in the adult rat by means of a peripheral nerve graft introduced into the spinal cord by dorsal approach]. AB - In the adult Mammal, different types of neurons, whose processes have been damaged in the CNS, may regrow lengthy axons along autologous PNS grafts. In the present study, PNS bridges were used to join the spinal cord (C5 level) to a nearby skeletal muscle (m. longissimus atlantis) which was denervated prior to direct graft insertion into an aneural region. From 3 to 5 months later, the following results were obtained: in situ and in vitro electrical stimulation of the graft determined partial or full contraction of the reconnected muscle. Intracellular recordings showed miniature endplate potentials (mepps). Endplate potentials (epps), evoked by stimulating the nerve graft, were recorded at the same points after partial blockade of the transmission with low doses of curare. They were suppressed with higher concentrations. The overall appearance of cross semithin and thin sections of the grafts was typical of regenerating nerves. EM observations of reinnervated muscles revealed typical neuromuscular junctions located either around the site of grafting or in the site of original endplates. In situ HRP application to the transected PNS bridges led to extensive labeling of neuronal somata located, close to the site of grafting, in the spinal grey matter and in adjacent spinal ganglia. When HRP was injected into the recommended muscle, neuronal labeling was almost restricted to typical motoneurons of the ventral horn. These results indicate that spinal neurons, and especially motoneurons, are probably involved in the formation, through PNS grafts, of new functional cholinergic connections with denervated skeletal muscles. PMID- 3103883 TI - [Transfer of R plasmids between Shigella and E. coli strains in the intestine of patients with acute shigellosis]. PMID- 3103884 TI - [Relation between limiting the size of myocardial infarct and heart function improvement]. PMID- 3103885 TI - [The role of leukocytes in the pathogenesis of microcirculatory disorders during shock]. PMID- 3103886 TI - [A contrast study on systolic time interval and heart volume index in congenital heart disease before and after radical operations]. PMID- 3103887 TI - [Sister chromatid exchange rate in detecting susceptible individuals to esophageal cancer]. PMID- 3103888 TI - [Serosa typing in gastric cancer and its significance]. PMID- 3103889 TI - [Study on an associated antigen of human nasopharyngeal carcinoma by immunofluorescent cytochemistry with monoclonal antibodies]. PMID- 3103890 TI - [Reactivity of the monoclonal antibody ALT-04 and an experimental study on its use in tumor-localization]. PMID- 3103891 TI - [Radiocerebellogram in the diagnosis of vertebrobasilar artery ischemia]. PMID- 3103892 TI - [Catheter closure of patent ductus arteriosus: experience in the management of 14 cases]. PMID- 3103893 TI - [Advances in research on the immunopathogenic mechanism of lymphatic filariasis]. PMID- 3103894 TI - Infantile hypophosphatasia fibroblasts proliferate normally in culture: evidence against a role for alkaline phosphatase (tissue nonspecific isoenzyme) in the regulation of cell growth and differentiation. AB - To explore the hypothesis that alkaline phosphatase (ALP) functions in the regulation of cell growth and differentiation, we examined in tissue culture several parameters of cell proliferation demonstrated by dermal fibroblasts from patients with infantile hypophosphatasia--a heritable form of rickets/osteomalacia which is characterized biochemically by marked deficiency of activity of the "tissue nonspecific" (bone/liver/kidney) ALP isoenzyme. Methylumbelliferyl phosphate was used as the fluorogenic substrate to assay ALP activity in cell homogenates from patients and age-, sex-, and passage-matched control cells. The nature of the enzymatic defect in the patient fibroblasts involved their failure to increase the specific activity of ALP during growth to confluency. Patient cell monolayers contained, on average, about 2-3% of control ALP activity (several lines consistently demonstrated less than 1%). Nevertheless, patient cells grew normally both in early and late passage, and in either serum-containing or defined medium. Contact inhibition appeared to be intact in the patient fibroblasts, since the protein and DNA content of their culture dishes were similar to controls just as the cells became visually confluent, and when examined 1 week after they reached monolayer. Light and phase contrast microscopy revealed no abnormalities in the appearance of patient cells during growth or at confluency. The mean volume of proliferating patient cells was also normal. Despite profound deficiency of constitutive ALP activity, dermal fibroblasts from infants with hypophosphatasia exhibit normal growth parameters in cell culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103895 TI - Effects of continuous 17 beta-estradiol administration on the periosteal and corticoendosteal envelope activity in spayed beagles. AB - Histomorphometric analyses of resorptive and formative parameters of the periosteal and corticoendosteal bone envelopes were performed on ribs from intact, spayed and spayed 17 beta-estradiol-supplemented Beagle dams. Dynamic formative features were evaluated after 2 pulses of in vivo tetracycline administration. The results indicated that following oophorectomy there was an increase in resorptive surfaces on the periosteum and corticoendosteum, and a decline in formative activity on these same envelopes. With continuous 17 beta estradiol supplementation, the resorptive surfaces on both the periosteum and corticoendosteum of the spayed dams decreased. The formative activity on the periosteum seemed to decline further after the administration of 17 beta estradiol, while on the corticoendosteum it tended to be restored to the level obtained for the intact dams. The increase in mineralization lag-time detected on the periosteum following oophorectomy appears not to be corrected by continuous 17 beta-estradiol supplementation in the spayed dams. PMID- 3103896 TI - Actin and myosinlike structure induced in the growth cartilage by acute ischemia. AB - Acute ischemia was induced in the lower limb of growing dogs by injecting the femoral artery with a suspension of carborundum and ground glass in physiological saline. This resulted in the loss of the cellular pattern and the cartilaginous matrix in the growth cartilage. The production of myofibrillike material was observed only in the growth cartilage as well as in the intertrabecular spaces of metaphysis in the injected leg. PMID- 3103897 TI - Vertebral bone resorption in vitro: effects of parathyroid hormone, calcitonin, 1,25 dihydroxyvitamin D3, epidermal growth factor, prostaglandin E2, and estrogen. AB - We have developed and characterized a new bone resorption system to test the effect of estrogen on vertebral bone in vitro. Neonatal mouse vertebral bones prelabeled with 45Ca were maintained in stationary tissue culture for 60-108 hours at 37 degrees C in 5% CO2/air. Each vertebral bone measured approximately 1 mm X 1 mm. Hormonal treatments were added directly to the incubation medium. The morphological appearance of these bones, before and after the onset of resorption, was examined by scanning electron microscopy. Bone resorption was measured by determining the % of the bone 45Ca released into the incubation medium. Vertebral bone resorption was stimulated in a dose-dependent manner by parathyroid hormone (1-100 nM), 1,25 dihydroxyvitamin D3 (0.0325-3.25 nM), and prostaglandin E2 (3-3000 nM). Epidermal growth factor (300 ng/ml) produced a small stimulation of bone resorption which was not inhibited by indomethacin (0.5 microM). Likewise, indomethacin (0.5 microM) did not inhibit PTH-stimulated vertebral bone resorption. Calcitonin (6.6 nM) produced a 79% inhibition of bone resorption induced by PTH (10 nM), whereas estradiol (up to 3 microM) did not inhibit bone resorption. Our results demonstrate that estrogen does not have a direct effect on vertebral bone tissue in vitro. This new bone culture system is a sensitive assay for the direct effects of resorptive agents on vertebral bone. PMID- 3103898 TI - Monofluorophosphate is hydrolyzed by alkaline phosphatase and mimics the actions of NaF on skeletal tissues, in vitro. AB - These studies were intended to assess the osteogenic activity of monofluorophosphate (MFP) in vitro, and to identify the enzyme(s) responsible for MFP hydrolysis-alkaline phosphatase (ALP) and/or acid phosphatase (AcP). ALP and AcP activities were determined by hydrolysis of p-nitrophenylphosphate (PNPP) at pH greater than 8 and pH 5.5, respectively, and MFP hydrolysis was determined, between pH 5.5 and pH 9.0, from measurements of [fluoride ion], using an ion specific electrode. We found (1) that MFP was an alternative substrate for purified ALP, but not for AcP; (2) that MFPase activity in the embryonic chick resembled ALP, but not AcP, with respect to pH-dependent hydrolysis, sensitivity to effectors (r = 0.98, P less than .001), and tissue distribution (r = 0.96, P less than .001); and (3) that intestinal MFPase activity in the embryonic chick co-purified with ALP activity (r = 0.93, P less than .01) and resembled ALP, but not AcP, in its distribution along the small intestine, being highest in the duodenum and lowest in the distal ileum (r = 0.96, P less than .001). We also found that in vitro exposure to MFP increased (1) the proliferation rate of embryonic chick calvarial cells in serum-free monolayer cultures (i.e., 3[H] thymidine incorporation into DNA, P less than .001); (2) ALP activity in calvarial cells (P less than .005) and in intact calvaria (P less than .05); and (3) collagen production by intact calvaria (i.e., 3[H]-proline incorporation as 3[H]-hydroxyproline, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103899 TI - Calcium phosphate precipitation in aqueous suspensions of phosphatidylserine containing anionic liposomes. AB - Liposomes prepared from 6.3:1.8:0.9:1.0 molar mixtures of phosphatidylcholine, dicetyl phosphate, cholesterol, and phosphatidylserine, respectively, (PS(+) liposomes) were compared with similarly prepared liposomes without the phosphatidylserine (PS(-) liposomes) for their effect on calcium phosphate precipitate formation in aqueous solutions at pH 7.4 and 22 degrees C. The liposomes, encapsulated with 50 mM phosphate (PI), were suspended in buffered 2.2 mM CaCl2, 0 or 1.5 mM KH2PO4 solutions and made permeable to Ca2+ fluxes with the ionophore, X-537A. External solution Ca2+ losses were found to be small in both PS(+) and PS(-) liposome suspensions when no ionophore was added. Even with 1.5 mM PI in the external solution, these losses did not exceed 0.2 mM. However, inoculating both liposome preparations with X-537A resulted in rapid, appreciable losses in solution Ca2+. Previous studies showed that in PS(-) liposomes, these latter losses were due to calcium phosphate precipitation, with the precipitate confined to the interior of the liposomes when no external PI was present, but extending to outside the liposomes when the suspending medium was rendered metastable. In the present study, Ca2+ losses resulting from intraliposomally confined precipitation were found to be marginally greater in PS(+) liposomes due primarily to a larger volume of entrapped PI available for reaction in these liposomes. However, with the addition of PI to the external solution, the reverse was observed, i.e., considerably less Ca2+ was lost in PS(+) than in PS(-) suspensions, a result of markedly less X-537A-induced precipitate forming outside PS(+) liposomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103900 TI - Effects of parathyroid hormone on odontogenesis of the mouse embryonic molar tooth in vitro. AB - Mandibular first molars of 17-day-old mouse embryos were cultured in vitro to examine the histological effects of various concentrations of parathyroid hormone (PTH) on odontogenesis of the molars. PTH did not affect the cytodifferentiation of mesenchymal cells into preodontoblasts but inhibited that of preodontoblasts into odontoblasts. Consequently, the odontoblasts failed to undergo dentinogenesis. On the other hand, inner enamel epithelium achieved terminal cytodifferentiation into secretory ameloblasts and these cells partially formed enamel in spite of the absence of dentin. All treated molars showed the same histological disturbances and these effects were independent of PTH dose. The present study indicated that PTH had an influence on mesenchyme-derived cells, inhibiting both the differentiation of odontoblasts and the formation of predentin and dentin. PMID- 3103901 TI - Influence of accompanying anion on intestinal radiocalcium absorption. AB - To assess directly the effect of ionic dissociation on the bioavailability of calcium, we used the double isotope inverse convolution method to compare the absorption of calcium gluconate and calcium pyrrolidone carboxylate, an organic, highly dissociated salt. Two tests were performed at a 2 day interval, using in random sequence either salt as a carrier. Forty-eight subjects of various age and clinical condition were studied. The use of the more dissociated salt consistently and significantly increased fractional absorption in a rather constant ratio. Moreover, it slowed absorption in normal subjects whatever their age, and accelerated it in patients with chronic renal failure or osteoporosis, leading to inferences on the alteration of calcium absorption in these conditions. PMID- 3103902 TI - Central 6-hydroxydopamine and renal sodium retention in mineralocorticoid-treated rats. AB - Cerebroventricular administration of 6-hydroxydopamine attenuated the development of deoxycorticosterone hypertension in the rat but did not affect the initial period of renal sodium retention. However, escape from the sodium retention was greater in 6-hydroxydopamine-treated rats. These data support the hypothesis that destruction of central catecholamine-containing neurons influences the renal handling of sodium. The enhanced escape may lead to diminished total body sodium, which attenuates the development of deoxycorticosterone hypertension. PMID- 3103903 TI - Travel advice from embassies and consulates of developing countries. PMID- 3103904 TI - Buserelin treatment of advanced prostatic carcinoma. Long-term follow-up of antitumor responses and improved quality of life. AB - The safety and efficacy of buserelin, a luteinizing hormone-releasing hormone (LH RH) agonist, was tested in 33 evaluable patients with Stages C or D adenocarcinoma of the prostate. With a minimum follow-up duration of 10 months, there was one complete response and 22 partial responses (69%) by National Prostatic Cancer Project criteria, with a median duration greater than 18 months. Six patients (18%) had stable disease, median duration greater than 25 months, and only 12 patients have progressed. Performance status improved in 67%, patient scored pain improved in 75%, and quality of life improved in 58%. Symptoms occurring during treatment consisted of hot flashes, loss of libido, and impotence. Buserelin produces a high frequency of durable objective and subjective responses in patients with advanced prostatic carcinoma. PMID- 3103905 TI - Anticancer drug distribution in lymph and blood during adjuvant chemotherapy after surgery for gastric carcinoma. A study with a combined preparation of 1-(2 tetrahydrofuryl)-5-fluorouracil and uracil. AB - Previously the authors reported that the fat emulsion of 1-(2-tetrahydrofuryl)-5 fluorouracil, tegafur (FT-207), yielded significantly higher concentrations of tegafur in the lymph and plasma compared to tegafur enteric-coated granules (FT G). However, the emulsification did not improve the metabolic conversion rate of tegafur to 5-fluorouracil (5-FU). A study was performed to assay the plasma and lymphatic concentrations of tegafur, 5-FU, and uracil in seven patients after radical surgery for gastric carcinoma who were given a combined oral preparation of FT-207 and uracil (UFT). Both lymph and plasma 5-FU levels after UFT were 20 times greater than those after FT-G, although FT-207 levels were not different. Patients given UFT showed significantly greater 5-FU and uracil concentrations in the lymph compared with the plasma. The results of this study suggest a potential use of UFT as an adjuvant postoperative chemotherapeutic agent for gastric carcinoma. PMID- 3103906 TI - Cytogenetic clones in a recurrent neurofibroma. AB - Chromosome studies were performed on a plexiform neurofibroma arising in a probable von Recklinghausen's disease patient, who also showed a de novo constitutional reciprocal translocation, t(1;22)(p32;q11). Banding analysis of the metaphases obtained from two primary cultures in vitro showed the presence of five cytogenetic clones, characterized by different chromosomal rearrangements. In addition to t(1;22), marker chromosomes involved pairs 1, 2, 3, 5, 8, 9, 10, 12, 16, and X. These findings suggest a possible polyclonal evolution in this neurofibroma. PMID- 3103907 TI - Effect of housing stress on the formation and development of tumors in rats. AB - Tumor induction by 7,12-dimethylbenz[a]anthracene (DMBA) or inoculation with adenocarcinoma cells was studied in rats raised in groups (group G) or individually (group I) as well as in rats raised in groups and switched to individual housing at the beginning of the experiment (group G/I). The number of DMBA-induced tumors did not differ among the three groups of female rats but tumor weight was lowest in group I, highest in group G/I and intermediate in group G. The mean weight of adenocarcinoma cell-induced tumors was highest in group G/I and did not differ between groups I and G. Male rats generally showed higher tumor weights than females, the values becoming significant in group G/I. The results show that housing and sex can significantly affect tumor growth. PMID- 3103908 TI - Chronic 12-O-tetradecanoylphorbol-13-acetate treatment prevents restoration of collagen loss associated with its inflammatory effect on mouse skin. AB - The extracellular matrix of the dermis is subject to severe alterations during tumor promotion with phorbol esters in mouse skin. The metabolic changes also involve general stimulation of protein synthesis and most specifically an increase of collagen synthesis. During chronic treatment with the tumor promoting phorbol esters 12-O-tetradecanoylphorbol-13-acetate (TPA) and 12-O retinoylphorbol-13-acetate (RPA) increased protein synthesis was observed that did not occur during treatment with the non-promoting mitogens 4-O-methyl-TPA and Ca-ionophore A 23187. Relative collagen synthesis measured as the ratio of radioactivities in hydroxyproline and proline or as the proportion of total radioactivity in pepsin resistant material was elevated, too, but not sufficiently to substitute for TPA-induced collagen loss. In contrast collagen degradation caused by the non-promoting irritant A 23187 is followed by an immediate, substantial increase of collagen synthesis. When TPA treatment was discontinued after a few applications insufficient for tumor development rapid resynthesis of collagen took place. Therefore we assume that continued phorbol ester application not only caused connective tissue damage but also prevents the repair of that damage. This effect seems to be promoter specific and contributes to the disruption of dermal-epidermal interactions during tumor promotion. PMID- 3103909 TI - Killing and mutation of human lymphoblast cells by aflatoxin B1: evidence for an inducible repair response. AB - Diploid human lymphoblast cells exhibit apparent saturation of mutation induced by exposure to aflatoxin B1, despite a linear increase in the amount and proportion of the aflatoxin-DNA adducts formed. The saturation is neither a cell cycle phenomenon nor a result of a genetically heterozygous population. Examination of the biphasic nature of aflatoxin-DNA adduct loss in vivo shows initial, rapid removal of all adduct species, followed by a slow loss of the aflatoxin-N7-guanine adduct alone. We hypothesize that these data reveal two modes of adduct loss in these cells. The first is an inducible, error-free system that is short-lived, turning off as adduct levels fall below the induction threshold of some 1000 total adducts/cell. The second loss is slower and results from spontaneous depurination of remaining aflatoxin-N7-guanines. Our data are in agreement with the possibility that apurinic sites thus generated are responsible for the mutation observed. A major paradox arises from the fact that aflatoxin related premutagenic depurinations are estimated to be only 10% of the number of spontaneous depurinations estimated by others to occur in human cells in a 1-h period. PMID- 3103910 TI - N-glucuronidation of carcinogenic aromatic amines catalyzed by rat hepatic microsomal preparations and purified rat liver uridine 5'-diphosphate glucuronosyltransferases. AB - The N-glucuronidation of three carcinogenic aromatic amines (4-aminobiphenyl, alpha-naphthylamine, and beta-naphthylamine) was investigated in hepatic microsomal preparations from two rat strains. In preparations from Wistar rats, individual variability was observed for the glucuronidation of the arylamines. This variability correlated with high and low levels of 3 alpha-hydroxysteroid UDP-glucuronosyltransferase (UDPGT) in hepatic microsomal preparations from Wistar rats. This individual variability was not observed in Sprague-Dawley rat hepatic microsomal preparations because hepatic 3 alpha-hydroxysteroid UDPGT levels do not vary in this strain of rats. Five highly purified rat liver UDPGTs were investigated for their ability to catalyze the conjugation of the aromatic amines. Of the purified enzymes investigated, only 3 alpha-hydroxysteroid UDPGT catalyzed the glucuronidation of 4-aminobiphenyl. alpha-Naphthylamine and beta naphthylamine conjugations were catalyzed by 3 alpha-hydroxysteroid, 17 beta hydroxysteroid, and 3-methylcholanthrene-inducible p-nitrophenol UDPGTs. The three aromatic amines did not serve as substrates for purified digitoxigenin monodigitoxoside or phenobarbital-inducible morphine UDPGTs. The results show that N-glucuronide formation can be catalyzed by UDPGT isoforms which also catalyze the formation of O-glucuronides. In addition, variable levels of 3 alpha hydroxysteroid UDPGT in Wistar rat liver may have toxicological significance for substrates of this isoenzyme. PMID- 3103911 TI - Localization of estrogen-induced DNA adducts and cytochrome P-450 activity at the site of renal carcinogenesis in the hamster kidney. AB - Renal carcinoma in male Syrian hamsters, induced by chronic administration of estradiol for 5-7 months, is known to arise in the cortex at the cortico medullary junction. In this in vivo model for hormonal carcinogenesis, estrogen induced covalent DNA adducts have previously been observed in whole kidney and have been postulated to be involved in tumor induction. In the present study, the intrarenal distribution of estrogen-induced DNA modification and estrogen metabolizing enzymes were investigated in male Syrian hamsters to ascertain a role of metabolism and adduct formation in estrogen-induced carcinogenesis. The highest estrogen-induced DNA adduct concentrations as measured by 32P postlabeling analysis were found in the renal cortex of hamsters treated with estradiol for 7 months. Total adduct levels in medullary DNA were approximately one-half of those found in cortex. Cytochrome P-450 enzymes were detected only in microsomes of kidney cortex (approximately 0.8 +/- 0.6 nmol P-450/mg protein) but not medulla of untreated male Syrian hamsters. Prostaglandin endoperoxide synthase activity in kidney cortical microsomes was 1/5 of the activity found in medullary microsomes. Thus, microsomal cytochrome P-450 levels and estrogen induced DNA adduct formation were highest in hamster kidney cortex, the origin of renal tumorigenesis. It is postulated that estrogen metabolism by cytochrome P 450 enzymes leading to covalent DNA modification plays a role in hormonal carcinogenesis in the hamster kidney. PMID- 3103912 TI - Antimyoclonic action of piracetam. AB - Five patients with myoclonus were treated with oral piracetam (8-9 g/day). All patients had action-sensitive and/or stimulus-sensitive myoclonus and enhanced amplitude of somatosensory evoked potentials. Piracetam produced a marked reduction of the myoclonus in the five subjects without side effects. In view of its excellent tolerance and synergism with other antimyoclonic drugs, we consider piracetam to be a very valuable drug for the treatment of patients with myoclonus of any origin. PMID- 3103913 TI - Synthesis of 2,6-anhydro-S-[ethylmercury(II)]-1-thio-D-glycero-L-manno-heptitol+ ++ and bis(2,6-anhydro-1-thio-D-glycero-L-manno-heptitol)mercury(II), and the study of their interaction with beta-D-galactosidase from E. coli. AB - Two competitive inhibitors of beta-D-galactosidase activity, namely, 2,6-anhydro S-[ethylmercury(II)]-1-thio-D-glycero-L-manno-heptitol (4) and bis(2,6-anhydro-1 thio-D-glycero-L-manno-heptitol)mercury(II) (6), with inhibition constants of 8.0 X 10(-4) M and 1.9 X 10(-4) M, were synthesized. Compound 6 was incorporated into the crystalline enzyme by cocrystallization. The stoichiometry of the enzyme inhibitor complex was 1:4, corresponding to one molecule of inhibitor per active site of the enzyme. Compound 4 was found to be unstable against X-ray irradiation, whereas compound 6 was submitted to X-rays for several days without any radiation damage. PMID- 3103914 TI - Antimetastatic effect of Lactobacillus casei YIT9018 (LC 9018) on a highly metastatic variant of B16 melanoma in C57BL/6J mice. AB - The effect of Lactobacillus casei YIT9018 (LC 9018) on a highly metastatic variant of B16 melanoma, B16-BL6, was determined in C57BL/6 mice. Intralesional (i.l.) injection of LC 9018 inhibited tumor growth and prolonged the survival after s.c. inoculation of B16-BL6 into C57BL/6 mice. Injection of LC 9018 i.v. protected the mice against pulmonary metastasis after i.v. inoculation of B16 BL6. Injection of LC 9018 i.l. before surgical excision of the primary tumor inhibited axillary lymph node metastasis and i.v. injection of LC 9018 after surgical excision of the primary tumor inhibited both axillary lymph node and lung metastases. On the other hand, the combination of i.l. and i.v. injections of LC 9018 markedly inhibited both lymph node and lung metastases. Natural killer cell activity of axillary lymph node cells was augmented by the injection of LC 9018 into a front footpad, while the cytolytic activity of axillary lymph node cells was significantly enhanced. However, the cytolytic activity was diminished by depleting whole lymph node cells of the plastic adherent cells. Furthermore, alveolar macrophage-mediated cytotoxic activity was augmented by the i.v. injection of LC 9018. PMID- 3103915 TI - [Heart transplant patients: outlines for the prevention, diagnosis and therapy of rejection, infections and other complications]. PMID- 3103916 TI - Coronary thrombolysis with tissue-type plasminogen activator. AB - Although the value of reperfusion has not yet been convincingly established in humans, initial data with precise end points appear to indicate salutary effects. t-PA will have a clear role in the initial phase of treatment of myocardial infarction, but it must be administered promptly, and residual stenosis must be evaluated and treated if reocclusion is to be prevented. Optimum therapy may involve concomitant pharmacologic agents as well as mechanical or surgical intervention. Long-term goals must address the underlying pathophysiology of coronary atheromata formation and thrombogenesis and primary prevention. PMID- 3103917 TI - Clinical pharmacology of coronary thrombolysis. AB - Pharmacologic thrombolysis is dependent on activation of endogenous plasminogen to the active proteolytic enzyme, plasmin. Agents such as tissue-plasminogen activator with a high affinity for fibrin bound plasminogen result in high local concentration of plasmin. Thus, they achieve clot lysis with less tendency to induce a systemic lytic state reflecting extensive fibrinogenolytic activity in the circulation. Appropriate dose regimens for thrombolytic agents in specific clinical situations is critical to maximize therapeutic efficacy while minimizing the risk of significant bleeding. PMID- 3103918 TI - Coronary thrombolysis: practical considerations. AB - The decision to administer thrombolytic agents to patients with acute myocardial infarction requires consideration of both the potential risks and benefits of treatment. In patients treated very early (1 to 2 hours) after the onset of infarction, benefit has been established. In those presenting later, factors such as age, location of infarction, the interval from the onset of symptoms to treatment, and any risks of therapy need to be weighed. This article will review the selection of patients for treatment, the state of the art for its implementation, and for the use of adjunctive therapies. PMID- 3103919 TI - Activation of the fibrinolytic system. AB - The fibrinolytic system is activated either directly or indirectly by proteins that convert plasminogen to plasmin in the circulation, within the interstitices, and on the surface of fibrin clots, or both. Agents that activate circulating and clot-bound plasminogen comparably induce a systemic lytic state accompanying clot lysis. Agents that activate plasminogen in the domain of fibrin preferentially exhibit clot selectivity. Fibrinolytic activators are assayed by detection of protein, generally immunologically, or of functional activity, generally by visualization of lysis of fibrin or by spectrophotometric determination of amidolytic activity. PMID- 3103920 TI - Factors contributing to the emergence of coronary thrombolysis. AB - Coronary thrombosis is now recognized as the most common proximate cause of acute myocardial infarction, and thrombolysis is evolving as an accepted therapeutic approach to patients presenting in the early stages of myocardial infarction. The ascent of thrombolysis in treatment hierarchies reflects multiple factors, including improved understanding of the pathophysiology of myocardial infarction, advances in the characterization of thrombosis and thrombolysis, the availability of clot-selective thrombolytic agents, the widespread availability of safe arteriographic procedures, and the contemporaneous development of effective percutaneous balloon angioplasty. Selection of patients most likely to benefit from thrombolysis with the lowest risk for complications remains difficult. Undoubtedly, some patients will benefit greatly from an aggressive approach to evolving myocardial infarction. PMID- 3103921 TI - Antibody to CB-peptide, alpha 2-CB (3,5), from type I collagen is a tissular marker of matrix degradation in hepatic murine schistosomiasis. PMID- 3103922 TI - Isolation and preparation of acellular schistosomal granuloma (periovular matricial complex, PMC). PMID- 3103923 TI - The relationship between the morphology of cell organelles and kinetics of the secretory process in male sex accessory glands of mice. AB - Two male sex accessory glands of the mouse, seminal vesicle and coagulating gland, were compared with the aim of relating differences in the morphology of organelles to the kinetics of the secretory process. The epithelial cells of the two glands were assessed by morphometric analysis, cytochemical staining, and electron-microscopic autoradiography after administration of a labeled amino acid. The rough endoplasmic reticulum of the seminal vesicle comprised narrow parallel cisternae, while that of the coagulating gland was greatly distended and occupied a much larger percentage of the cytoplasmic volume. Radioactively labeled products were secreted much more rapidly in the seminal vesicle than in the coagulating gland. The primary point of difference in kinetics of intracellular transport between the two glands was in exit of material from the rough endoplasmic reticulum. The more rapid drainage of the rough endoplasmic reticulum may be related to its relatively greater membrane surface density and lesser internal volume. In contrast, similarities in size and cytochemical staining in the Golgi apparatus of the two glands were accompanied by similar kinetics of intracellular transport of secretory protein through this organelle. PMID- 3103924 TI - Identification of the calmodulin-binding components in canine cardiac sarcolemma. AB - The covalent attachment of 125I-calmodulin to canine cardiac sarcolemma has been achieved using the crosslinker dithiobis(succinimidyl propionate). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the crosslinked products revealed three 125I-calmodulin-labeled components of Mr = 125,000, 108,000 and 81,000. That the formation of these three components was Ca-dependent and inhibited by unlabeled calmodulin, or calmodulin antagonists, would indicate that the formation of these components was calmodulin-specific. The size of these 125I labeled components was unchanged over a range of crosslinker or 125I-calmodulin concentrations indicating that they represent 1:1 complexes between 125I calmodulin (Mr = 17,000) and Mr = 108,000, 91,000 and 64,000 sarcolemma components respectively. The labeling of these components with 125I-calmodulin was not enhanced when endogenous calmodulin was removed from sarcolemma. The possible identity of the 125I-calmodulin-labeled sarcolemma components is discussed. PMID- 3103925 TI - Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation. AB - pp60c-src is phosphorylated in vivo at tyrosine 527, a residue not present in pp60v-src (its transforming homolog), and not at tyrosine 416, its site of in vitro autophosphorylation. To test the hypothesis that tyrosine phosphorylation regulates pp60c-src biological activity, we constructed and studied pp60c-src mutants in which Tyr 527 and Tyr 416 were separately or coordinately altered to phenylalanine. Tyr----Phe 527 mutation strongly activated pp60c-src transforming and kinase activities, whereas the additional introduction of a Tyr----Phe 416 mutation suppressed these activities. Tyr----Phe 416 mutation of normal pp60c-src eliminated its partial transforming activity, which suggests that transient or otherwise restricted phosphorylation of Tyr 416 is important for pp60c-src function even though stable phosphorylation is not observed in vivo. PMID- 3103926 TI - Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. AB - To investigate the importance of tyrosine phosphorylation in the regulation of pp60c-src, we have substituted phenylalanine for tyrosine at positions 416, 519, and 527. Cells expressing the 527 or the 519/527 mutant but not the 416 or the 519 mutant were morphologically transformed, grew in soft agar, and formed foci. In addition, the 527 and 519/527 mutants had elevated kinase activities in vitro. Modifying Tyr 416 to phenylalanine in the 527 or the 519/527 mutants only partially inhibited their kinase activities yet abolished their ability to induce focus formation and promote growth in soft agar. These results suggest that two events must occur to activate the full transforming potential of pp60c-src: hypophosphorylation at Tyr 527 and hyperphosphorylation at Tyr 416. PMID- 3103927 TI - Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain. AB - We introduced two mutations into the carboxy-terminal regulatory region of chicken pp60c-src. One, F527, replaces tyrosine 527 with phenylalanine. The other, Am517, produces a truncated pp60c-src protein lacking the 17 carboxy terminal amino acids. Both mutant proteins were phosphorylated at tyrosine 416 in vivo. The specific activity of the Am517 mutant protein kinase was similar to that of wild-type pp60c-src whereas that of the F527 mutant was 5- to 10-fold higher. Both mutant c-src genes induced focus formation on NIH 3T3 cells, but the foci appeared at lower frequency, and were smaller than foci induced by polyoma middle tumor antigen (mT). The wild-type or F527 pp60c-src formed a complex with mT, whereas the Am517 pp60c-src did not. The results suggest that one, inability to phosphorylate tyrosine 527 increases pp60c-src protein kinase activity and transforming ability; two, transformation by mT involves other events besides lack of phosphorylation at tyrosine 527 of pp60c-src; three, activation of the pp60c-src protein kinase may not be required for transformation by the Am517 mutant; and four, the carboxyl terminus of pp60c-src appears to be required for association with mT. PMID- 3103928 TI - Synthetic immunomodulators and synthetic vaccines. AB - Efforts have been made for several years to obtain well-defined, nontoxic adjuvants and antigens which could be used for human vaccination and immunostimulation. Among synthetic adjuvants, MDP represents one of the most studied family of compounds. This molecule is the minimal active structure of whole Mycobacteria and has been shown to be endowed with numerous biological activities. MDP is adjuvant active, increases nonspecific resistance against infectious challenges and, under certain conditions, increases resistance against tumor grafts. Moreover, MDP has other pharmacological properties such as pyrogenic and somnogenic activities. Several hundred MDP derivatives have been synthetized and some of the biological activities have been dissociated. One MDP derivative presently under clinical trials has been shown to be adjuvant active but is devoid of pyrogenicity. The mechanisms of activity of these MDP and derivative molecules will be discussed. More recently, synthetic antigens which are copies of natural epitopes, have been shown to induce protective antibodies against bacterial or viral pathogens. These synthetic antigens conjugated to synthetic carriers or to synthetic adjuvants such as MDP, may permit the preparation of totally synthetic vaccines. PMID- 3103929 TI - Enterococci and aminoglycosides: evaluation of susceptibility and synergism of their combination with piperacillin. AB - Some clinical isolates of enterococci were tested for susceptibility to gentamicin, tobramycin, amikacin and netilmicin. Five percent of Streptococcus faecalis tested demonstrated high level resistance (minimum inhibitory concentration (MIC) greater than 2024 micrograms/ml) to gentamicin, tobramycin and netilmicin, while amikacin had MICs greater than 128 micrograms/ml for all strains tested. Since a combination of a beta-lactam and streptomycin does not produce synergism against all strains of enterococci for an increase in the number of highly resistant strains, the effect of piperacillin plus gentamicin, tobramycin, and netilmicin was examined. The combination piperacillin + netilmicin seemed to be very effective against all enterococci tested. PMID- 3103930 TI - Emerging microorganisms in cystic fibrosis. AB - Pseudomonas aeruginosa is the most common bacterial isolate obtained from patients with cystic fibrosis of the lungs. Recently, however, new multiresistant organisms have emerged, whose identification may be difficult and whose pathogenic role proves hard to define. Of the 71 strains isolated from 24 patients with cystic fibrosis during acute flareups of pulmonary symptoms, 48 turned out to be Pseudomonas aeruginosa (67.6%); 11 were Pseudomonas non aeruginosa (15.5%); and 12 were Achromobacter xylosoxidans (16.9%). Each bacterial isolate was tested for sensitivity to nine antibiotics (ceftazidime, azlocillin, piperacillin, aztreonam, cefsulodin, cefoperazone, amikacin, tobramycin, and sisomycin) in terms of minimum inhibitory concentration and minimum bactericidal concentration values. In this series, Achromobacter xylosoxidans proved the species least responsive to treatment, and ceftazidime the most active antibiotic both against Achromobacter and against strains of the genus Pseudomonas. Twenty-three different associations of ceftazidime with aminoglycosides, tested for activity on the multiresistant strains, failed to show synergism of action. PMID- 3103931 TI - Roxithromycin (RU 28965) in the treatment of respiratory tract infections. AB - The clinical efficacy of roxithromycin, administered at the daily dosage of 300 mg (150 mg every 12 hours), was evaluated in 25 patients with respiratory tract infections, mostly infectious exacerbations of chronic bronchitis. Pathogens isolated before treatment were Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus beta-haemoliticus, Haemophilus influenzae. Clinical cure or improvement was achieved in 21 out of 22 evaluable patients. The eradication rate was 91%. Tolerability was good: two patients reported gastrointestinal side effects which caused treatment discontinuation. These preliminary data suggest that roxithromycin may have a place in the treatment of respiratory infections. PMID- 3103932 TI - Chemotherapy of advanced gastric carcinoma (stage IV): a randomized study of FAM versus 5-FU plus BCNU. AB - Forty-six patients with advanced gastric carcinoma (Stage IV) were evaluated in a prospective randomized comparison of two chemotherapy regimens (FAM versus 5-FU plus BCNU) to identify therapeutic activity. Treatment groups were well balanced with respect to known prognostic factors. Thirty-three patients had measurable disease and thirteen had only microscopic residual disease in the resection margins. The overall median survival of the entire group was 13.2 months. Two (6%) patients with measurable disease reached complete response (CR), 1 (3%) partial response (PR), 12 (36%) had stable disease (SD) and 18 (56%) had progressive disease (PD). The responders had not reached the median survival yet, the patients with SD had a median survival of 14.7 months and the PD 9.5 months. In the FAM arm there were 3 (18%) responders (2 CR and 1 PR), 7 (41%) SD and 7 (41%) PD, versus O responders, 5 (31%) SD and 11 (69%) PD in the 5-FU plus BCNU arm. In the FAM arm the median survival was 15.7 months versus 9.9 months in the other therapeutic arm. The statistical analysis indicated that survival associated with FAM regimen was superior to that reached with the 5-FU plus BCNU regimen. Thirteen patients with unmeasurable disease had a median survival of 15.9 months. PMID- 3103933 TI - Effects of the lipid peroxidation product 4-hydroxynonenal on the aggregation of human platelets. AB - The stimulation by ADP or arachidonic acid of the aggregation of human platelets in plasma was inhibited by 4-hydroxynonenal (HNE). This reduction of aggregation was time related, and was increased by prolonged preincubation of the platelets with the aldehyde. HNE was more potent than its homologue 4-hydroxypentenal (HPE). HNE was less active in decreasing the aggregation induced by calcium ionophore A23187 or collagen in comparison with ADP. HNE was inactive against aggregation of platelet-rich plasma (PRP) stimulated by thrombin whereas it potently inhibited the aggregation of washed platelets in response to both thrombin and collagen. Platelets were found to degrade HNE, and mechanisms additional to covalent binding to glutathione are indicated by the results obtained. The aldehydes, including HNE, generated by platelets originated principally from arachidonic acid metabolism. PMID- 3103935 TI - Reaction and inhibition mechanisms of aldose reductase from rabbit lens. PMID- 3103934 TI - Product inhibition of benzo[a]pyrene metabolism in uninduced rat liver microsomes: effect of diol epoxide formation. AB - Conversion of benzo[a]pyrene (BP) to BP 7,8-dihydrodiol 9,10-oxides (DE) (measured as 7,10/8,9-tetrols) by untreated (UT) rat liver microsomes is over 10 times slower than following 3-methylcholanthrene (MC) induction. Time courses have been subjected to a kinetic analysis analogous to that previously reported for metabolism by MC-induced microsomes (J. Biol. Chem., 259 (1984) 13770-13776). Competition between BP and 7,8-dihydrodiol for P-450 is the major determinant of the rate of DE formation. Glucuronidation of quinones and phenols only increases the isolated BP metabolites including DE by 40%. This indicates far less inhibition by these products than for metabolism in MC-microsomes (4-6-fold). Thus stimulation may result from a decreased quinone-mediated oxidation of metabolites. In the presence of DNA, UT-microsomes metabolize BP to approximately equal amounts of 9-phenol-4,5-oxide (9-PO) and DE/DNA adducts. Addition of uridine diphosphoglucuronic acid (UDPGA) fails to enhance modification of DNA by DE, but formation of the 9-PO adduct is reduced as a result of lower free 9 phenol levels. The kinetic characteristics of BP metabolism by UT-microsomes are highly sensitive to the presence of very small but variable amounts (2-25 pmol/mg) of the very active cytochrome P-450c, which is the predominant form in MC-microsomes. The major effect of elevated levels of P-450c is an 8-fold increase in DE formation at low concentrations of BP due to a lowering of Km (7.9 2.6 microM) and an increase in the regioselectivity for DE formation from 7,8 dihydrodiol (5-15% of total BP metabolites). The formation of DE was directly correlated with the content of P-450c (r = 0.94). The presence of increased levels of P-450c in UT-microsomes is probably due to previous exposure of the animals to environmental inducers and is minimized by controlled housing and feeding. PMID- 3103936 TI - Intestinal absorption characteristics of 5-fluorouracil, ftorafur and 6 mercaptopurine in rats. PMID- 3103937 TI - Characteristics of augmentation of cell-mediated cytotoxic activities by recombinant human interferon-gamma (Met-Gln form): a comparative study with natural human interferon-alpha and -beta. PMID- 3103938 TI - Reconstitution of Apo-DT-diaphorase with flavin-adenine dinucleotide. PMID- 3103939 TI - The structures of additional teleocidin class tumor promoters. PMID- 3103940 TI - Genetic control of glycolipid expression. AB - A polymorphic variation of sialic acid species of sialosyllactosylceramide was found in dog erythrocytes. The analysis of the glycolipids in the erythrocytes of the individual dogs in a family of a Japanese breed of dog, Shiba-Inu, showed that the expression of sialosyllactosylceramide containing N-glycolylneuraminic acid was an autosomal dominant trait over the expression of that containing N acetylneuraminic acid. Polymorphic variations of major liver gangliosides were also found in various strains of inbred mice. The strains were classified into three groups; the first group possessed only II3 NeuGc-LacCer, the second group possessed II3NeuGc-GgOse3Cer in addition to II3NeuGc-LacCer and the third group possessed II3NeuGc-GgOse4Cer and II3NeuGc,IV3NeuGc-GgOse4Cer as well as the above two gangliosides. By subjecting mice of these three groups to genetic analysis, the strain of the first group (WHT/Ht mice) was demonstrated to be a recessive homozygote which had a single autosomal defective gene making it unable to express N-acetylgalactosaminyltransferase activity to produce II3NeuGc-GgOse3Cer. The strains of the second group (BALB/c and C57BL/10 mice) were also demonstrated to be recessive homozygotes which had a single autosomal defective gene making them unable to express high enough level of galactosyltransferase activity to produce II3NeuGc-GgOse4Cer. By the analysis of gangliosides and the enzyme activity of H-2 congenic mice and mice produced by a mating, this defective gene controlling the expression of II3NeuGc-GgOse4-Cer through the regulation of the transferase activity was demonstrated to be linked to H-2 complex on chromosome 17. PMID- 3103941 TI - [Serodiagnosis of schistosomiasis mansoni using an egg extract semi-purified by precipitation with ammonium sulfate]. AB - Fifty one sera from bilharziosis patients and thirty control sera were examined with a Schistosoma mansoni egg antigen purified by precipitation with ammonium sulphate at 50% saturation. Sensitivity and specificity were good and showed a good correlation with results obtained by MSA1 antigen, but antigen tested is far more easier to prepare than MSA1. PMID- 3103942 TI - [Unusual manifestation of retinal involvement in Fabry's disease]. PMID- 3103943 TI - The effect of the Bain circuit on gas exchange. AB - This is an experimental and theoretical analysis of the Mapleson D (Bain) circuit. A bench model was used to determine the effects of breathing rate, tidal volume, and fresh gas flow on the simulated alveolar gas composition when a commercial Bain breathing circuit is used. In addition, an effort was made to derive mathematical equations that describe the CO2-profile in the expiratory limb of the Bain circuit, the amount of CO2 rebreathed, and the effect of this rebreathing on the alveolar gas composition. Data obtained with the bench model and with the equations were compared to data from the literature. The effect of the Bain circuit on gas exchange was compared to that of an equivalent dead space. PMID- 3103944 TI - Moyamoya disease--a review of clinical experience and anaesthetic management. AB - Moyamoya disease is a rare neurovascular condition that affects both children and adults. Increasingly these patients present for surgical management to improve the cerebral circulation since medical therapy is essentially ineffective. Because of the precarious cerebral circulation, these patients represent an anaesthetic challenge. In this report we review the pathophysiology of moyamoya disease, summarize our experience with seven patients and discuss the anaesthetic management. PMID- 3103945 TI - Phorbol ester-induced formation of clastogenic factor from human monocytes. AB - Phorbol-12-myristate-13-acetate (PMA) acts as a tumor promoter on mouse skin. It induces inflammation and leukocyte-mediated clastogenicity which appears to be related to rapid changes in lipid metabolism. To identify lipids possessing clastogenic and/or tumor-promoting properties, we have characterized the metabolism and release of arachidonic acid (AA) and related lipids during the formation of lipophilic clastogenic factors by PMA-treated human monocytes. In 1 h, [3H]AA-labeled monocytes spontaneously released significant amounts of their total radioactivity (4%) which increased nearly 4-fold (15%) with PMA (30 ng/ml) treatment. Eighty-five per cent of extracellular 3H-label from both control and PMA-treated monocytes was composed of free AA (plus AA-metabolites), while the remaining radioactivity was incorporated in phospholipids and mono- and diacylglycerols. Treated and non-treated cells released essentially the same kind of metabolites but PMA induced a 3- to 4-fold increase in total amounts. The major products consisted of prostaglandins F2 alpha and E2, thromboxane B2, 12 hydroxy-5,8,10-heptadecatrienoic acid and 5-, 11- and 15-hydroxyeicosatetraenoic acids. PMA also induced increases in the levels of three unidentified products. Neither leukotrienes nor 4-hydroxynonenal, a major alkenal degradation product of AA, were found in medium from PMA-treated monocytes. PMA, in contrast to the first-stage tumor promoter calcium ionophore A23187, failed to stimulate the release of platelet activating factor. The increased formation of phorbol ester induced AA metabolites was proportional to the increase in free extracellular AA. The source of AA from treated and untreated monocytes consisted of cellular phospholipids with phosphatidylcholine and phosphatidylethanolamine accounting for 85%. PMID- 3103946 TI - Prostaglandin H synthase-dependent mutagenic activation of heterocyclic aromatic amines of the IQ-type. AB - Microsomes from ram seminal vesicles known as a rich source of prostaglandin H synthase (PHS) activate the food mutagen IQ (2-amino-3-methylimidazo[4,5 f]quinoline) to (a) product(s) mutagenic in Salmonella typhimurium TA98. The activation is dependent on the PHS cofactor arachidonic acid and is strongly inhibited by the PHS inhibitor indomethacin. In this system, the mutagenic potency of IQ is 22 and 110 times higher than that of 2-aminofluorene and benzidine, respectively. The high mutagenic potency of IQ observed previously with mono-oxygenase activation is thus extended to the PHS system. The mutagenic activity produced by PHS increases for 4 h; this contrasts with the relatively short lifetime of the activity produced by mono-oxygenase and suggests that different agents are involved in the two processes. The PHS-mediated mutagenic activity of IQ is strongly dependent on the bacterial O-acetyltransferase which is defective in strain TA98/1,8-DNP6. Further, the responses of the strains TA1978 and TA1538 indicate that the mutagenic activity is dependent on lack of the bacterial DNA excision repair and independent of the plasmid pkM101 coded error-prone DNA repair system. Structural analogs of IQ without a methyl group on the imidazole ring and with a naphthalene instead of the quinoline ring show greatly diminished PHS-mediated mutagenic activity. The strain response pattern and structure-activity relationships are similar to those found with mono oxygenase activation of IQ and thus indicate a basic similarity of the IQ activation via PHS with that via mono-oxygenase. It is hypothesized that PHS may activate carcinogenic heterocyclic aromatic amines in vivo. PMID- 3103947 TI - Structure-activity studies of the indole alkaloid tumor promoter teleocidins. AB - New teleocidin derivatives with various substituents at positions 2, 5 and 7 of the indole ring were prepared from (-)-indolactam V, which is the fundamental structure of teleocidins and has a tumor-promoting activity, to examine the contribution of the alkyl substituents of teleocidins to the activity. Their possible tumor-promoting activities in vivo were evaluated by Epstein-Barr virus early antigen-inducing activity and inhibition of specific binding of [3H]TPA to a mouse epidermal particulate fraction. These two biological activities correlated well for each derivative. Large substituents at positions 2 and 5 remarkably lowered the activities, indicating that the structural requirements for the activities of these domains are especially strict. To investigate in detail the contribution of position 2 of (-)-indolactam V to the activities, new microbial metabolites, (-)-2-oxy-indolactam V, and blastmycetin B and C, were also tested. These compounds proved to be inactive, suggesting that the double bond at position 2 plays an important role for the activities. Substituents at position 7 generally enhanced the activities and even blastmycetin A, which is a dimer of (-)-indolactam V, showed high activities. The effects of the substituents on binding ability to the 12-O-tetradecanoylphorbol-13-acetate receptor were analyzed quantitatively using physicochemical substituent parameters and regression analysis. The results exhibited the fact that hydrophobicity of the substituents plays a critical role for receptor binding, and supported the hypothesis that the monoterpenoid moiety of teleocidins is involved in the non-specific hydrophobic interaction with phospholipids in cell membrane. PMID- 3103948 TI - R-goitrin- and BHA-induced modulation of aflatoxin B1 binding to DNA and biliary excretion of thiol conjugates in rats. AB - Previous studies have shown that dietary R-goitrin is a potent inducer of hepatic glutathione S-transferase (GST) and epoxide hydrolase activities but has no effect on components of the mixed function oxidase system (ethoxycoumarin O deethylase and cytochrome P-450). In the present work effects of dietary R goitrin (200 p.p.m.) or butylated hydroxyanisole (BHA) (7500 p.p.m.) on GST activity, binding of aflatoxin B1 (AFB1) to DNA, in vivo, and biliary excretion of thiol conjugates of AFB1 in rats were studied. Increases of GST activities (1.9- and 2.1-fold) were accompanied by reductions in AFB1-DNA binding (43% and 85%) and increases (1.7- and 2.2-fold) in biliary excretion of AFB1-thiol conjugates in R-goitrin and BHA groups, respectively. Microsomal aflatoxin 8,9 epoxidase activities were not increased in either treatment group. The role of GST induction in the carcinogenesis of AFB1 and the anticarcinogenic potential of R-goitrin are discussed. PMID- 3103949 TI - Isolation of alkylating agent-sensitive Chinese hamster ovary cell lines. AB - Six derivatives of a Chinese hamster ovary cell line have been isolated by selection for hypersensitivity to the cytotoxic effects of the monofunctional alkylating agent methyl methane sulphonate (MMS). These cells are up to 6-fold more sensitive to MMS than the parental line, as estimated from D37 values, and are cross-sensitive to methyl nitrosourea, as well as to the ethyl derivatives of these drugs. Comparisons of their sensitivities to the bifunctional alkylating agents cis-platinum (II) diammine dichloride, mitomycin C and melphalan reveals marked phenotypic diversity, with only one mutant, designated MMS-2, exhibiting appreciable hypersensitivity to all of these agents. No striking hypersensitivity to radiation or to the purine analogue caffeine is apparent in any of the mutant lines. Based on their profiles of sensitivity to DNA damaging agents, it would appear that these mutants are phenotypically unlike any previously described mammalian cell mutants and probably represent a number of different genetic complementation groups. These mutants may facilitate an investigation into the mechanisms of repair of alkylation damage in mammalian cells and could prove to be suitable hosts for the cloning of human DNA repair genes. PMID- 3103950 TI - The effect of intravenous thrombolytic therapy on left ventricular function: a report on tissue-type plasminogen activator and streptokinase from the Thrombolysis in Myocardial Infarction (TIMI Phase I) trial. AB - In Phase I of the NHLBI trial of Thrombolysis in Myocardial Infarction (TIMI), 290 patients admitted within 7 hr after onset of acute infarction were randomly assigned to intravenous treatment with either streptokinase (SK) or recombinant tissue-type plasminogen activator (rt-PA). Left ventricular function was measured from contrast ventriculograms in 145 patients with both pretreatment and predischarge studies analyzable. Regional wall motion in the infarct site was measured by the centerline method and expressed in units of standard deviations (SDs) from the mean motion in 52 normal subjects. Patients treated with rt-PA (n = 77) achieved a significantly higher reperfusion rate after 90 min of treatment. Perfusion of the infarct-related artery improved from visual grade 0 or 1 (total occlusion or penetration without perfusion) to grade 2 or 3 (partial or full reperfusion) in 62% receiving rt-PA vs 31% receiving SK (n = 68) (p less than .001). However, the ejection fraction did not change significantly from before treatment to before discharge in either treatment group (+0.7 +/- 6.7% vs +1.0 +/ 8.3%, respectively). A small but significant increase in regional wall motion was observed in each of the two groups (+0.4 +/- 0.8 vs +0.3 +/- 0.8 SD/chord, respectively; each p less than .001 compared with baseline). This was countered by declines in the hyperkinesis of the noninfarct region (-0.3 +/- 1.0 SD/chord [p = .01] compared with baseline and -0.2 +/- 1.0 SD/chord [p = .23], respectively). Analysis of the combined groups revealed that the ejection fraction increased only in patients who achieved reperfusion by 90 min after onset of therapy or who had subtotal occlusions initially. There was greater recovery of left ventricular function in patients who achieved reperfusion earlier vs later than 4 hr after symptom onset and in patients with vs without some collateral circulation to the infarct-related artery. PMID- 3103951 TI - Reduction in infarct size and enhanced recovery of systolic function after coronary thrombolysis with tissue-type plasminogen activator combined with beta adrenergic blockade with metoprolol. AB - The effect of beta-adrenergic blockade on the salvage and functional recovery of reperfused myocardium was investigated in anesthetized dogs. Immediately after thrombotic occlusion of the left anterior descending coronary artery, the cardioselective beta-blocking agent metoprolol was given intravenously at a dose of 0.5 mg/kg infused over 10 min. One hour after the onset of occlusion, recanalization was initiated by intravenous infusion of recombinant human tissue type plasminogen activator (rt-PA, 10 micrograms/kg/min for 30 min). Anatomic infarct size expressed as percent of the left ventricular mass (I/LV), global ejection fraction, and mean systolic shortening of the segmental radii (SS) of the infarcted area were measured either after 24 hr or 1 week in six groups of six dogs each: group I (rt-PA + metoprolol, evaluated at 24 hr), group II (rt-PA + metoprolol, evaluated at 1 week, group III (rt-PA alone, evaluated at 24 hr), group IV (rt-PA alone, evaluated at 1 week), group V (persistent occlusion, evaluated at 24 hr), and group VI (persistent occlusion, evaluated at 1 week). The smallest infarcts were found in reperfused dogs given metoprolol, but the differences from dogs receiving rt-PA alone were not statistically significant (I/LV, expressed as mean +/- SEM: 5.5 +/- 0.9% in group I, 6.7 +/- 1.9% in group II, 15.4 +/- 5.0% in group III, 11.4 +/- 3.5% in group IV, 23.6 +/- 2.5% in group V, and 26.9 +/- 2.3% in group VI).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3103953 TI - Rapid determination of alpha-amylase activity by use of a new chromogenic substrate. AB - A new chromogenic substrate that is blocked at the nonreducing end, 4,6 benzylidene-alpha-D-4-nitrophenylmaltoheptaoside, is used to determine alpha amylase (EC 3.2.1.1) activity in serum in a coupled assay with alpha-glucosidase (EC 3.2.1.20) and glucoamylase (EC 3.2.1.3) as auxiliary enzymes. The duration of the lag phase between 25 and 37 degrees C is less than 90 s, and the molar absorptivity of 4-nitrophenol is constant. The main cleavage product of the substrate by human pancreatic and salivary alpha-amylase is 4 nitrophenylmaltoside; in the presence of the auxiliary enzymes, greater than 95% of hydrolyzed substrate is accounted for as 4-nitrophenol. The combined reagent is stable for at least 20 days at 2-8 degrees C; precision is good, with CVs ranging from 1.7 to 3.3%; and the correlation of results with those by the 4 nitrophenylmaltoheptaoside method is excellent. Heparin (40 kilo-int. units/L), ascorbic acid (2.8 mmol/L), bilirubin (430 mumol/L), hemoglobin (170 mumol/L), glucose (55 mmol/L), and triglycerides (11 mmol/L) do not interfere in the assay. PMID- 3103952 TI - Evaluation of lipoproteins and apolipoproteins in serum of a Tangier patient by micro-scale two-dimensional electrophoresis. AB - We examined lipoproteins and apolipoproteins in serum of a Tangier-disease patient. We used three different techniques of micro-scale two-dimensional electrophoresis: (a) no denaturants; (b) with sodium dodecyl sulfate (SDS) used only in the slab gel electrophoresis; (c) and with urea and a detergent used in isoelectric focusing and with SDS in slab gel electrophoresis. By technique a, an extremely low concentration of high-density lipoproteins (HDL) in the Tangier serum was seen, and lipoproteins that cannot form HDL complexes were detected as multiple spots in the acidic (pl 4 approximately 5) and relatively low apparent molecular mass (20,000 approximately 80,000) region. By technique b, Tangier low molecular-mass lipoproteins were dissociated into their constituent apolipoproteins, and we observed a higher proportion of apoC-III, together with lower proportions of apoA-I and apoA-II, than in the normal HDL fraction. Technique c showed the total content of apolipoproteins in the whole Tangier serum, as several workers have reported. The presence of low-molecular-mass lipoproteins and a high concentration of apoC-III in this lipoprotein fraction characterized the Tangier serum. PMID- 3103954 TI - Periodic sharp complexes in herpes simplex virus encephalitis: survival in an elderly man. AB - For the electroencephalographer, focal temporal periodic complexes have been strongly associated with herpes simplex virus encephalitis (HSVE). The appearance and subsequent disappearance of these complexes has generally been held to herald a poor prognosis. This report involves an elderly man with HSVE who survived with no neurologic deficits despite the presence and later disappearance of periodic sharp complexes. This supports the view that the periodic complexes are more a function of the pathophysiologic changes caused by HSVE as opposed to a marker of tissue injury. PMID- 3103955 TI - Periodic lateralized epileptiform discharges in a patient with definite multiple sclerosis. AB - The occurrence of PLEDs is described in a patient with definite, long-standing multiple sclerosis and the rarity of such an association is emphasized. PMID- 3103956 TI - EEG in whiplash: a reappraisal. AB - Sixty-eight patients with symptomatic cervical whiplash injuries, who did not receive head trauma, had standard electroencephalograms performed with a time span of 1 day to 2 years after the occurrence of the accident. Minimal EEG abnormalities were found in a small number of patients. Plain x-rays, computerized tomography or radionuclide brain scans failed to demonstrate associated structural abnormalities. Twenty-five of the group had 24-hour EEG cassette recordings; 15 of the latter reported specific symptoms of their post traumatic syndrome during the test but no abnormal EEG correlates were established. Sixteen patients had long-term follow-up studies and no example was encountered of early or late onset post-traumatic epilepsy. These findings contradict previous reports of the greater incidence and severity of EEG abnormalities in patients that have sustained whiplash neck injuries in isolation (no head trauma). PMID- 3103957 TI - Mental retardation in a patient with Maroteaux-Lamy. AB - An 8-year-old boy with Hurler-like traits including severe mental retardation excreted in his urine a pathognomonic amount of dermatan sulfate. Less than 10% residual activity of arylsulfatase B was found in his leucocytes and fibroblasts. Hurler fibroblasts corrected an abnormally high 35SO4-incorporation into acid mucopolysaccharides (MPS) in cultured fibroblasts, whereas Maroteaux-Lamy fibroblasts did not. The patient thus has a rare combination of Maroteaux-Lamy and severe mental retardation. PMID- 3103958 TI - Chemotactic activity in aqueous humor from patients with anterior uveitis. AB - Anterior uveitis, inflammation of the iris or ciliary body of the eye, may be associated with a variety of systemic diseases. Although a leukocytic infiltrate is characteristic of anterior uveitis, few studies have sought to detect factors in aqueous humor that could attract neutrophils or monocytes into the anterior chamber. Using modified Boyden chambers, we found that a 5% concentration of aqueous humor from patients with anterior uveal inflammation induced monocyte movement comparable to optimal or near-optimal concentrations of C (complement)5a or platelet-derived growth factor. Aqueous humor from patients with anterior uveitis induced significantly more monocyte migration than did aqueous humor from two sets of controls (either patients undergoing cataract extraction or patients with posterior uveitis). "Checkerboard" or gradient analysis indicated that a majority of inflammatory disease samples induced monocyte chemotaxis (directed migration) while the control aqueous humor consistently induced chemokinesis (stimulated random migration) (P less than 0.02). Despite their ability to induce monocyte migration, samples tended to induce minimal neutrophil migration with the exception of aqueous humor that was obtained from one patient with acute anterior disease. This sample induced marked chemokinesis. Identification of chemotactic activity may clarify the pathogenesis of uveitis and the characterization of leukocyte migration factors in aqueous humor may help define subsets of anterior uveal inflammation. PMID- 3103960 TI - Neurofibromatosis and Albright's syndrome. AB - For both NF and Albright's syndrome, the pathogenetic relationships between the various elements of the respective syndromes remain a mystery, and the importance of nontumorous endocrine abnormalities in neurofibromatosis has, in my opinion, been overstated. Nonetheless, the parallel between the two disorders is striking, and the consistent occurrence of skin and skeletal dyplasias in both suggests that a search for the fundamental defect in either can be advanced by focusing on what is common to these two types of tissue. For example, how does one reconcile a disturbance of the melanosome with skeletal aberrations? An answer to that question will put us on the right track. One final question must be asked. Are neurofibromatosis and Albright's syndrome alternate manifestations of the same disorder? In a trivial sense, the answer may be yes. That is, in at least some instances, one condition may have been mistaken for the other, and thus a factitious overlap or "sameness" misconstrued. Upon closer scrutiny, however, there are two important points that would cast doubt on a positive response to this question: Neurofibromatosis, or at least neurofibromatosis I, is heritable as an autosomal dominant trait, whereas heritability has not been documented for Albright's syndrome; and I am unaware of reported cases that describe both disorders, diagnosed by criteria beyond cafe au lait spots and bone dysplasia, in one and the same individual, although such a case has been shared with me by S. A. Sorensen, M.D., of the Genetics Institute of Copenhagen, Denmark. The full reporting of such a case would be of great interest. PMID- 3103959 TI - Requirements for activation of human peripheral blood T cells by mouse monoclonal antibodies to CD3. AB - The present study was undertaken in an attempt to reconcile the conflicting results concerning the signals required for the activation of human resting T cells by antibodies to the T-cell receptor/CD3 complex (Ti/CD3). For this purpose we have used highly purified peripheral blood T cells, depleted of monocytes and of preactivated Ia + T cells, to the extent that they were unable to proliferate to interleukin 2 (IL-2) alone or to optimal doses of phytohemagglutinin (PHA). To further minimize the contribution of contaminating monocytes, we used the anti CD3 mAb, Leu-4, and cells from Leu-4 nonresponder subjects, whose monocytes we show completely fail to bind the Leu-4 mAb. The parameters of T-cell activation which we measured were rises in intracellular free calcium ion [Ca2+]i, IL-2 receptor expression IL-2 production, and cell proliferation. Our results indicate that induction of proliferation of resting T cells requires at least two signals. Signal one is best delivered by multivalent anti-CD3 mAb, such as Leu-4 mAb covalently linked to Sepharose 4B (Seph-Leu-4), or with Leu-4 mAb and anti-mouse IgG. These reagents crosslink the CD3 receptor complex on the T cell, and result in a rise in intracellular [Ca2+]i, in expression of receptors for IL-2, and in proliferation upon addition of IL-2. In contrast, purified T cells exposed to soluble Leu-4 mAb do not exhibit a rise in intracellular [Ca2+]i, do not express receptors for IL-2, and do not proliferate upon addition of IL-2, indicating that the valency of anti-CD3 mAb is critical for the delivery of the first activation signal to the T cell. The essential step of crosslinking of CD3 antigens on T cells by anti-CD3 mAb is normally mediated by monocytes which have bound anti-CD3 mAbs via their Fc receptors. Monocytes from Leu-4 nonresponder subjects, which we show fail to bind Leu-4 mAb, fail to crosslink CD3 antigens on T cells, resulting in failure of T-cell activation. The second signal needed for the proliferation of T cells whose Ti/CD3 complexes are crosslinked is IL-2. IL-2 production by such T cells required a monocyte delivered signal, which must be delivered to these T cells simultaneously with the crosslinking of their Ti/CD3 antigens. This IL-2-inductive signal can be delivered by both Leu-4 nonresponder and Leu-4 responder monocytes, indicating that delivery of this IL-2 inductive signal is independent of anti-CD3 mAb binding by monocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3103961 TI - Comparative study on Lewis lung tumor lines with 'low' and 'high' metastatic capacity. II. Cytochemical and biochemical evidence for differences in glycosaminoglycans. AB - The enhanced metastatic capacity of an in vivo selected Lewis lung tumor line (LLT-HH) was correlated with changes in cell-associated glycosaminoglycans (GAG) using ultrastructural cytochemistry, flow cytometry and biochemistry. The increase in highly sulphated GAG content on the cell membrane of LLT-HH cells compared to the parent LLT cells was demonstrated cytochemically. Using in vitro [3H]glucosamine labelling of GAG components it was shown that the LLT-HH cells were characterized by a high production of heparan sulphate while the parent LLT line had a high hyaluronic acid-chondroitin sulphate production. The high metastatic phenotype is accompanied by an altered production of cell-associated GAGs. PMID- 3103962 TI - Characterization of metastasis-associated antigens on RAW117 lymphosarcoma cell lines. AB - A syngeneic murine model system was used to study the immunobiology of metastasis. The highly malignant RAW117-H10 cell line was compared to the less malignant parental RAW117-P cell line from which it was derived, for expression of cell surface antigens. Using rabbit antisera, two major glycoprotein antigens were detected on the tumor cell surfaces. Antigen-I was uniformly distributed over the surface of these cells whereas antigen-II had a patchy, punctate distribution. Antigen-I was displayed less on RAW117-H10 cells than on RAW117-P cells, while the expression of the other serologically distinct antigen (antigen II) was increased on RAW117-H10 cells compared to the less malignant parental (RAW117-P) cells. This differential antigen expression was assessed by immunodiffusion, a 125I-labeled protein-A binding assay, flow cytometry and rocket immunoelectrophoresis. Both these antigens had a molecular weight of 70,000 daltons. Antigen-I bound the lectin concanavalin-A whereas antigen-II did not, suggesting that antigen-I might be the viral envelope glycoprotein gp70. The identity of antigen-II is presently unknown. Syngeneic Balb/c mice injected with highly malignant and metastatic RAW117-H10 cells coated with antiserum to antigen I were protected from early death; this effect was not seen with RAW117-H10 cells coated with antiserum to antigen-II. The opsonizing qualities of these antisera may be different due to antibody to antigen-II being shed more rapidly than antibody to antigen-I. PMID- 3103963 TI - Dynamic radiologic patterns of Paget's disease of bone. AB - Within the diaphyseal cortex, the primary resorption phase of Paget's disease is often limited either to the endosteum or to the central layers of the cortex. This results in primary resorption fronts that are usually discrete, both radiologically and scintigraphically. The subsequent activation of the subperiosteal cortex may be delayed, leading to secondary expanding fronts associated with subperiosteal new bone formation. Sequential radiographs of 19 untreated patients followed 6.4 +/- 1.2 years showed that the mean extension rate of the lesions within cortical bone was 8 +/- 0.5 mm/year per advancing front. This extension rate showed no significant change in 15 patients treated with calcitonin (CT) and/or ethane-1-hydroxy-1,1-diphosphonate (EHDP), but was significantly decreased in 14 patients treated with 3-amino-1-hydroxypropilidene 1,1-diphosphonate (APD). The increased remodeling rate of pagetic bone magnifies the radiologic changes due to mechanical, dystrophic, and metabolic interferences. Thus, a sclerotic pattern of the disease may rapidly change into a mixed or even a lytic pattern under the influence of any rarefying factor. Conversely, lytic pagetic bone may transform into dense bone through the administration of antiosteoclastic medications such as CT and APD. The reconstructive action of any new therapeutic regimen should be monitored radiologically. PMID- 3103965 TI - [A case of idiopathic hyperCKemia with CK-linked immunoglobulin (IgA-lambda)]. PMID- 3103964 TI - Skeletal distribution and biochemical parameters of Paget's disease. AB - Quantitative bone scans were performed with 99mTc-EHDP in 170 untreated pagetic patients (93 men, 77 women; mean age, 65.4 years). The distribution of 863 pagetic skeletal locations was analyzed. Bone scans demonstrated 8.3% more pagetic sites than roentgenograms. The extent of Paget's disease was evaluated in each patient by a scintigraphic skeletal index. This index correlated with serum alkaline phosphatase (SAP) and urinary hydroxyproline (HyPro) levels, and also with hypocalcemic acute response to calcitonin. The correlation of SAP with an index of activity (extent index adjusted by uptake ratios) was better than with the nonadjusted index. Only 30.6% of pagetic sites were responsible for clinical symptoms. No correlation was found between age and skeletal index of the disease. PMID- 3103966 TI - [Epiconus syndrome due to ossification of the lower thoracic yellow ligament]. PMID- 3103967 TI - [Alzheimer's paired helical filaments]. PMID- 3103968 TI - The effect of prolonged fasting and total parenteral nutrition on hepatobiliary imaging with technetium-99m DISIDA. AB - Prolonged fasting (NPO) and total parenteral nutrition (TPN) have been reported to result in an unacceptable number of false-positive hepatobiliary scintigrams for acute cholecystitis. Based on these reports, the clinical usefulness of the hepatobiliary scan in diagnosing acute cholecystitis in the critically ill postoperative patient who has been NPO or on TPN has been questioned. Patients who were either on prolonged fasting or total parenteral nutrition and who had no history of hepatobiliary disease were prospectively studied to assess the value of the Tc-99m diisopropyl-iminodiacetic acid (DISIDA) scan without pretreatment with cholecystokinin (CCK) in such a setting. Of the 17 persons studied, nine had been on total parenteral nutrition for at least five days and eight had been fasting for at least five days prior to imaging. Seven of the nine individuals on TPN (78%) and six of the eight individuals who were NPO (75%) had normal hepatobiliary scintigraphy. The results suggest that hepatobiliary imaging with Tc-99m DISIDA has a lower false-positive rate in individuals on TPN or NPO than previously has been reported and that it has clinical efficacy in ruling out the diagnosis of acute cholecystitis in these individuals. PMID- 3103969 TI - Research utility of noninvasive methods for measurement of cardiac output. AB - Two noninvasive methods of cardiac index (Q) determination, pulsed Doppler echocardiography (QDop), and CO2 rebreathing (QCO2) were compared to dye dilution in eight normal volunteers. Measurements of Q were made by dye dilution (QDD) and the two noninvasive techniques under the following conditions: supine rest, after inflation of cuffs around the thighs, 35-degree head-up tilt, supine rest repeated, during constant isoproterenol infusion, and after an intravenous bolus of propranolol. When mean Q values of the group for each intervention were compared, close agreement was observed between dye dilution and each noninvasive method (QDOP = 1.08 QDD - 0.07 L/min X m2, r = 0.99, SEE = 0.02; QCO2 = 0.68 QDD + 0.84 L/min X m2, r = 0.97, SEE = 0.02). Fair correlations were achieved when all 48 paired observations were analyzed (QDop = 1.00 QDD + 0.17 L/min X m2, r = 0.89, SEE = 0.17; QCO2 = 0.71 QDD + 0.77 L/min X m2, r = 0.79, SEE = 0.20). However, the Doppler ultrasound technique was significantly more precise in quantitating changes in Q in individual patients. These results demonstrate that estimates of Q can be made with reasonable accuracy by either CO2 rebreathing or Doppler echocardiography. However, the Doppler technique is a much more accurate means of quantitating acute changes in Q. PMID- 3103970 TI - Glyburide does not alter thyroid function. AB - Goiter and hypothyroidism have been reported as side effects of sulfonylurea therapy. To test the effects of glyburide, a new generation sulfonylurea drug, on thyroid function, we studied 15 male Type 2 diabetic patients before and after 6 weeks of treatment with this drug, and we repeated the studies on 9 of these patients who remained on the drug for at least 24 weeks. All hypoglycemic agents were discontinued for 1 week before the study. Patients had a baseline thyroid examination, serum T4, free T4 index (FT4I), T3, and free T3 index (FT3I), fasting serum glucose (FSG), HbA1c and a TRH test of TSH reserve. The dose of glyburide was adjusted at 2 weeks, and the tests were repeated after 6 weeks and after at least 24 (24-32) weeks of glyburide therapy. Compared to baseline, there was a significant decrease in FSG at 6 weeks and again at 24-32 weeks. Body weight, thyroid size, serum FT4I, FT3I, and TSH did not change significantly. After 6 weeks of therapy, there was no significant correlation of FSG or HbA1c with FT4I, FT3I, basal or peak TSH or TSH response area. The integrated area under the TSH response curve decreased significantly in 8 patients at 24 weeks (p less than 0.05). There was a positive correlation between FSG and the area under the TSH response curve using the combined baseline and 24 week data in these patients (r = 0.73, p less than 0.01). In this study with patients acting as their own controls, there was no effect of glyburide on thyroid function or size. PMID- 3103971 TI - Continuous subcutaneous insulin infusion (CSII) reduces counter-regulatory hormone concentrations in a patient receiving enteral hyperalimentation. AB - A 61-year-old male, while recovering from a Whipple's procedure for pancreatic carcinoma, was treated for 13 days with an insulin infusion pump for diabetes exacerbated by enteral hyperalimentation. Treatment with continuous subcutaneous insulin infusion resulted in improved blood glucose control. Associated with this improvement was a reduction in plasma cholesterol, triglyceride and free fatty acid levels. Plasma epinephrine, norepinephrine, glucagon and cortisol concentrations were also lowered although growth hormone levels remained unchanged. It is concluded that enhanced metabolic control during hyperalimentation results in a decrease in counter-regulatory hormone levels and an improvement in the catabolic state in this patient. These preliminary observations provide evidence for maintaining euglycemia in diabetic patients while receiving nutritional support. PMID- 3103972 TI - Effects of increasing glucose intake on nitrogen balance and energy expenditure in malnourished adult patients receiving parenteral nutrition. AB - The effects of increasing glucose intake on nitrogen balance, energy expenditure and fuel utilization were measured in malnourished adult patients receiving parenteral nutrition with constant nitrogen intake and high or low glucose intakes for 8 day periods. Energy balance, nitrogen balance, weight and temperature were determined daily. Blood samples taken at admission and at the end of days 7 and 8 of each diet were analysed for glucose, fatty acids, urea, insulin, glucagon and thyroid hormones. The effect of increasing glucose intake was to increase nitrogen balance by 0.28 +/- 0.08 (SEM) mg/kJ. A scheme is proposed, based on present and previous findings, of the separate effects of nitrogen and energy intake on nitrogen balance, permitting calculation of rates of repletion of fat and lean body mass from estimates of nitrogen intake and energy balance. Malnourished patients are shown to attain markedly positive nitrogen balances at zero or negative energy balances. Large errors in estimation of energy requirements have little effect on nitrogen balance. Changes in nitrogen balance were entirely due to changes in urea excretion. Creatinine excretion increased 12% with high glucose intake, attributed mainly to increased muscle mass (7%) and body temperature (4%). A 12% increase in resting energy expenditure was only partly due to costs of glycogen storage and lipogenesis; the remainder, about one-half, is probably due to glucose and insulin mediated increases in sympathetic activity. There were marked increases in 3,5,3' triiodothyronine (T3) concentrations with time, but no difference between the high and low glucose diets. The T3/thyroxine ratio, an index of free T3 concentration, increased much more rapidly on the high than on the low glucose diet. Changes in T3 could not account for the effect of glucose, under these conditions, to increase resting energy expenditure. PMID- 3103973 TI - Effects of variation of the tri-iodothyronine/reverse triiodothyronine ratio in vivo on the metabolic characteristics of subsequently isolated hepatocytes. AB - Reverse tri-iodothyronine (3,3',5'-tri-iodothyronine, rT3), a major product of the peripheral monodeiodination of thyroxine, was administered subcutaneously to fed rats at a dose of 100 micrograms/100 g body weight for 2 consecutive days. This dose induced a 17-fold increase in plasma rT3 (from 0.05 +/- SEM 0.01 to 0.85 +/- 0.11 ng/ml, P less than 0.001) whilst the plasma T3 concentration was decreased to half of the control value (0.40 +/- 0.03 to 0.20 +/- 0.02 ng/ml, P less than 0.01). As a result of these changes the T3/rT3 ratio was therefore decreased from 8.0 +/- 1.6 to 0.23 +/- 0.03 (P less than 0.001). Hepatocytes prepared from control or rT3-treated rats were incubated with [1-14C]oleate and the rates of 14CO2 release and glucose production were estimated. Despite the changes in ratio of T3 to rT3 observed in vivo, rates of 14CO2 release and glucose production rate from hepatocytes subsequently isolated were unchanged. PMID- 3103974 TI - Prospective payment for outpatient mental health services: evaluation of diagnosis-related groups. AB - General medical hospitals are applying diagnosis-related groups (DRGs) to define their case mix so as to make possible prospective estimates of costs per case. We apply DRGs to 1000 adults registered through an outpatient clinic. Results, based on 837 patients in eight DRGs, provide no reason to anticipate that DRGs or other selected variables thought to be associated with prognosis will help predict costs of most outpatient mental health care. We explain why these results should not be surprising, and we describe an alternative perspective that may be necessary in order to develop a viable prospective payment system that is based on costs per case. PMID- 3103975 TI - Species differences in methaemoglobin production after addition of 4 dimethylaminophenol, a cyanide antidote, to blood in vitro: a comparative study. AB - Methaemoglobin production after addition of DMAP to blood of various species, has been studied in vitro. The study was undertaken both with blood, as taken, and after equilibration with atmospheric oxygen. Considerable interspecies variation in methaemoglobin production was found. When the initial rate of methaemoglobin formation was considered only marmoset and human blood showed any marked degree of inhibition by equilibration with atmospheric oxygen. PMID- 3103976 TI - Lipid metabolic pathways operating in amphibian full-grown oocytes. AB - The utilization of (2-3H)-glycerol in lipid biosynthesis was analyzed in Bufo arenarum and Xenopus laevis full-grown oocytes. The precursor was more actively incorporated in Xenopus laevis oocytes. Neutral glycerides were the lipids displaying the highest levels of radioactivity followed by phosphatidylcholine and phosphatidylethanolamine. After reincubation of prelabeled oocytes in a saline buffer solution, a net fall in labeled phosphatidic acid concomitant with an increase in phosphatidylcholine were detected. The present findings establish that glycerolipid biosynthesis is operative in full-grown oocytes. In addition, Xenopus laevis oocytes seem to be metabolically more active. PMID- 3103977 TI - Predictability of sequence homologies among lysine-rich histones by immunological distance. AB - The relationship between immunological distance (I.D.) measured by microcomplement fixation and amino acid sequence difference for lysine-rich histones was tested using antisera to lysine-rich histones of known sequence, chicken H1 and H5, goose H5, and trout H1 as well as to trout H5. The best relationship between I.D. (y) and percent sequence difference (x) for lysine-rich histones, y = 2x, applies as well to other histones of known sequence but it differs from y = 5x, reported for other proteins and often used for histones. Although deviations indicate that I.D. is a poor predictor of primary sequence differences among histones, it suggests that trout H5 is more closely related to H1 than to chicken H5. PMID- 3103978 TI - Choice of antimicrobial drugs by the site of infection. AB - Microcomputer programs are designed in BASIC for the analysis of 1209 positive cultures and 1056 antimicrobial susceptibility tests on clinical specimens from various sites of infection. A list of antimicrobial drugs of choice by the site of infection is determined on the basis of the computer analysis of the data. The list may be useful to clinicians for initial therapy in critically ill patients and for preoperative prophylaxis before the results of cultures and susceptibility tests are reported. PMID- 3103979 TI - Aspects of thyroid function during use of Norplant implants. AB - Plasma thyroxin (T4), triiodothyronine (T3), T3-uptake and thyroid stimulating hormone (TSH) were measured in 18 women using Norplant implants or Norplant-2 implants for six months. Free T4-index and free T3-index were also calculated. All women had used non-hormonal contraceptives before insertion of the implants. T4 decreased and T3-uptake increased, indicating a lower level of thyroid binding proteins during treatment. Free T4-index remained unchanged, indicating that the free concentration of thyroxin was unaltered. All women were euthyroid and TSH was unchanged. It is concluded that treatment with Norplant implants does not result in a change in thyroid function. PMID- 3103981 TI - Molecular aspects of nitrogen fixation by photosynthetic prokaryotes. AB - The photosynthetic prokaryotes possess diverse metabolic capabilities, both in carrying out different types of photosynthesis and in their other growth modes. The nature of the coupling of these energy-generating processes with the basic metabolic demands of the cell, such as nitrogen fixation, has stimulated research for many years. In addition, nitrogen fixation by photosynthetic prokaryotes exhibits several unique features; the oxygen-evolving cyanobacteria have developed various strategies for protection of the oxygen-labile nitrogenase proteins, and some photosynthetic bacteria have been found to regulate their nitrogenase (N2ase) activity in a rapid response to fixed nitrogen, thus saving substantial amounts of energy. Recent advances in the biochemistry, physiology, and genetics of nitrogen fixation by cyanobacteria and photosynthetic bacteria are reviewed, with special emphasis on the unique features found in these organisms. Several major topics in cyanobacterial nitrogen fixation are reviewed. The isolation and characterization of N2ase and the isolation and sequence of N2ase structural genes have shown a great deal of similarity with other organisms. The possible pathways of electron flow to N2ase, the mechanisms of oxygen protection, and the control of nif expression and heterocyst differentiation will be discussed. Several recent advances in the physiology and biochemistry of nitrogen fixation by the photosynthetic bacteria are reviewed. Photosynthetic bacteria have been found to fix nitrogen microaerobically in darkness. The regulation of nif expression and possible pathways of electron flow to N2ase are discussed. The isolation of N2ase proteins, particularly the covalent modification of the Fe protein, the nature of the modifying group, properties of the activating enzyme, and regulating factors of the inactivation/activation process are reviewed. PMID- 3103980 TI - A morphometric study of the effect of oral norethisterone or levonorgestrel on endometrial blood vessels. AB - A morphometric study was undertaken to quantitate vessel numbers in uterine biopsies from a control group of patients, patients with dysfunctional uterine bleeding and patients taking low dose norethisterone or levonorgestrel. Vessels were counted at the endometrial/myometrial junction and in the functional endometrium just below the surface epithelium. The number of arteries at the endometrial/myometrial junction was found to be decreased in patients taking norethisterone and levonorgestrel. An increase was found in the total number of veins and in the number of dilated veins in the functional endometrium of the progestogen-treated specimens. Dilated veins were frequently found close to the endometrial surface and it is possible that they may be the major cause of the irregular bleeding associated with low dose oral progestogens. PMID- 3103982 TI - Flecainide acetate. PMID- 3103983 TI - Blunt spatula debridement and trifluorothymidine in epithelial herpetic keratitis. AB - 31 consecutive patients with laboratory proven epithelial herpetic keratitis were included in a prospective, controlled study evaluating combined blunt spatula debridement and trifluridine therapy versus trifluridine alone. A group of 20 patients treated by the combined method was compared in sequence with a group of 11 patients treated by trifluridine alone. Epithelial healing time was significantly shorter in the combined treatment group and treatment failures were less frequent. Blunt spatula debridement was well tolerated. Our findings tend to support the concept that combined treatment of herpetic epithelial keratitis by debridement and antiviral therapy is beneficial by shortening the course of epithelial lesions. PMID- 3103984 TI - Side effects in the treatment of herpetic keratitis. AB - Various side effects due to antiherpetic drugs observed in the last ten years in our department were studied. A total of 132 patients were treated with 5-iodo-2' deoxyuridine (IDU), 69 with trifluorothymidine (F3T), 58 with acyclovir (ACV) and 33 with adenine arabinoside (ara-A). Patch tests were routinely done when patients exhibited contact dermatitis. Of the patients treated with IDU, 3 (2.3%) showed contact dermatitis, 2 (1.5%) follicular conjunctivitis and 1 (0.8%) punctate keratopathy. Of the patients treated with F3T, 7 (10.1%) exhibited contact dermatitis and 1 (1.4%) follicular conjunctivitis. In the group treated with ACV, 2 (3.4%) patients showed punctate keratopathy. The patients who received ara-A did not show any side effects. We found that F3T caused contact dermatitis more frequently in Japanese people than Europeans. These side effects were resolved by switching to another anti-herpetic drug without the occurrence of cross-allergy. Therefore, switching to another drug is strongly recommended when patients exhibit side effects in the treatment of herpetic keratitis. Other complications were allergy to atropine and to drug preservative. PMID- 3103985 TI - The effect of modulating the synthesis of arachidonic acid cascade products on HSV lesion recurrence. AB - Induction of HSV lesion recurrence may be achieved by a variety of stimuli. Trauma of almost any kind (physical, chemical, electromagnetic and thermal) to the healed primary lesion site has been successful for induction of recurrence. In common with each of these mechanisms is the release of inflammatory mediators (arachidonic acid (AA), complement, kinins, etc.) following trauma. Because blockade of the AA cascade with steroids has been noted to abort HSV skin lesions, and because steroids have numerous side effects making them a poor therapeutic choice in ocular lesions, we decided to test several relatively different types of AA cascade inhibitory drugs in mouse ear HSV recurrence models. In this series of experiments, it was found that topical steroids gave the greatest initial decrease in lesion number (80% fewer than control on day 3 post recurrence induction (PRI), while meclofenamate resulted in the greatest reduction of lesions by day 5 PRI (85% fewer lesions than control and 60% fewer than the steroid treated group). The NDGA treated group exhibited the least reduction in recurrence severity (27% fewer lesions than control on day 5 PRI and 200% more lesions than the steroid group. Chlorpromazine (thorazine) acted roughly equivalent to the steroid treated group by day 5 PRI (70% fewer lesions than the untreated control group). Relative efficacy in lesion reduction between groups by day 5 PRI is: meclofenamate greater than steroid = chlorpromazine greater than NDGA greater than control. Meclofenamate, steroid and chlorpromazine significantly reduced lesions (p less than .05) when compared with the saline treated control mice. NDGA did not significantly reduce lesions by day 5 PRI. PMID- 3103986 TI - Localized subepidermal bullae after intravenous phenobarbital. AB - The occurrence of subepidermal bullae and sweat gland necrosis in barbiturate induced coma is well recognized. We report the case of a patient who received intravenous phenobarbital for refractory seizures and subsequently sustained subepidermal bullae without sweat gland necrosis in the skin around and proximal to the intravenous site. Although this may have been secondary to extravasation, a different mechanism of barbiturate-induced bulla formation may exist. PMID- 3103987 TI - Self-administration of bronchodilators. Cost effective? PMID- 3103989 TI - Cost-benefit comparison of aerosol bronchodilator delivery methods in hospitalized patients. AB - We compared two modes of aerosol bronchodilator delivery in 34 patients hospitalized with obstructive airways diseases. The standard mode, therapist administered up-draft nebulization (UDN), is labor-intensive and therefore relatively costly. The alternative mode, self-administration by a metered dose inhaler (MDI), is less costly, but its efficacy over an entire hospitalization has heretofore not been established. Patients were enrolled after transfer to the pulmonary ward from the emergency room or intensive care units (ICU). We then randomized them to receive metaproterenol q4h either via MDI or UDN. Daily spirometry revealed that MDI and UDN were associated with equivalent bronchodilation initially and equivalent improvement at discharge. The duration of hospitalization for the two groups was also the same. Thus, the two delivery methods were equally effective. We could not attribute this equivalence to pretreatment intergroup differences or to differences in concomitant therapy with steroids, theophylline, other bronchodilators, or antibiotics. Routine use of MDI rather than UDN in all non-ICU adult patients would save $253,487 per year at our institution alone. PMID- 3103988 TI - Occult mucous airway obstruction in diabetic ketoacidosis. AB - Four patients with diabetes mellitus and no underlying clinical pulmonary disease were found to have extensive unilateral mucous occlusion of a major central bronchus. None of the patients had significant auscultatory findings suggestive of pulmonary secretions, and chest roentgenographic films were normal. Arterial blood gas evaluation failed to reveal the usual hypocapnia during ketoacidosis, thus prompting bronchoscopic examination or deep airway suctioning. These interventions disclosed and resolved the mucous obstruction of the compromised bronchus. Antibiotic therapy, based upon bronchial secretion Gram stain and culture, was successfully instituted in all patients. Lethargy and autonomic neuropathy are proposed as contributing factors responsible for occult mucous plugging in diabetic patients in ketoacidosis. The absence of hypocapnia in this setting may be the only clue to silent mucous plugging of airways. PMID- 3103990 TI - In vitro activity of BMY-28142, a new cephalosporin. AB - BMY-28142 was compared in vitro with ceftazidime, cefotaxime and cefoperazone and was found to be more active against Pseudomonas aeruginosa and Staphylococcus aureus. Essentially no effect of increasing inoculum size 100-fold was seen-on MICs with BMY-28142 or ceftazidime; some effect was noted with cefotaxime and cefoperazone. PMID- 3103991 TI - A rapid method for the evaluation of new antituberculous agents. AB - Fifty-one new synthetic compounds belonging to four different series, namely (1a) substituted aryl-4-(substituted phenyl) succinimide; (1b) N-(substituted methyl) 4-(heterocyclic) succinimide; (2) heterocyclic 4-(5'-nitro-2-furyl) thiazoles; (3) substituted aryl-4-(3', 4'-dihydroxy phenyl) thiazoles, and (4) phenyl-N,N 1,2,3-bis-methoxy carbonyl guanidines were screened for antituberculous activity using a conventional broth dilution test (BDT) and a liquid scintillation radiometric method (LSRM). Eight compounds showed in vitro activity. LSRM showed 100% agreement with BDT. LSRM is completed within 60 h, while BDT requires 8-9 days. Unlike BDT, LSRM allowed one to measure the graded changes in the metabolism and the growth rate of Mycobacterium tuberculosis in response to various concentrations of the drug. It permits the measurement of the relative prolongation of the replication time by the drug or the test compound. With LSRM it was possible to detect the phase of growth during which the test compound shows or begins its antituberculous activity. It improves our understanding of the antituberculous activity of the test compound and hence is more advantageous. It is rapid, reliable, quantitative and more sensitive than BDT. LSRM is thus suitable for the evaluation of new drugs. PMID- 3103993 TI - The desmosomal plaque and the cytoskeleton. AB - Two major plasma membrane domains are involved in the architectural organization of the cytoskeleton. Both are junctions of the adherens category characterized by the presence of dense plaques associated with the cytoplasmic surface of their membranes. The plaques serve as specific anchorage structures for two different types of cytoplasmic filaments. Intermediate-sized filaments (IF) of several types, i.e. cytokeratin IF in epithelial cells, desmin IF in cardiac myocytes and vimentin IF in arachnoidal cells of meninges, meningiomas and several other cells, attach to the desmosomal plaques, whereas actin-containing microfilaments associate with non-desmosomal adhering junctions such as the zonula adherens, fascia adherens and punctum adherens. The plaques of both kinds of adhering junctions contain a common acidic polypeptide of Mr 83,000 identical to 'band 5 protein' of bovine snout epidermal desmosomes. However, other plaque components are mutually exclusive to one of the two subclasses of adhering junctions. The desmosomal plaque structure, which does not contain vinculin and alpha-actinin, comprises representatives of cytoplasmic, non-membrane-integrated proteins such as desmoplakin(s) and the cytoplasmic portions of transmembrane glycoproteins such as 'band 3 glycoprotein'. The analysis of both categories of junction associated plaques should provide a basis for understanding the establishment and the dynamics of junction-cytoskeleton interaction. PMID- 3103994 TI - An association between anti-inflammatory medication and internal pelvic fistulas. AB - Spontaneous internal fistulas involving intestine, rectum, bladder, or vagina in patients without predisposing illnesses were studied. Twelve of 20 (60 percent) were receiving steroids or other anti-inflammatory medication at the time the fistulas developed. Fifteen of the 20 patients subsequently had diverticular disease identified. It is proposed that there is an association between anti inflammatory medication and fistulas that develop from intestine to other pelvic viscera, spontaneously or in association with colonic diverticula. PMID- 3103992 TI - The ultrastructural morphology of native salivary gland chromosomes of Drosophila melanogaster: the band-interband question. AB - Native salivary gland chromosomes of Drosophila melanogaster, isolated without exposure to acid fixatives, have been examined in regions 1A-3B, 15A-17B, 19B-20D and 71E-73A and reveal improved aspects of preservation at the ultrastructural level. Three main points emerge: fine bands are well preserved allowing detection of some not recorded in maps made on classical acid-fixed preparations. Structures with the morphology of putative nascent ribonucleoprotein (RNP) particles are apparent in puffs, diffuse bands and virtually all interbands observed. At this level the morphology of native chromosomes is consistent with the hypothesis that all decondensed regions are members of a continuum of transcriptionally active structures. This notion is relevant to data obtained from other approaches to the band-interband question. (iii) Although the chromosomes have not been exposed to 45% acetic acid, at least some of the dark bands represented by the Bridges as doublets in their classical maps contain vacuoles which include putative RNP particles. PMID- 3103995 TI - Preventing complications in jejunostomy tube feedings. PMID- 3103996 TI - Assessment of the child with diabetic ketoacidosis. PMID- 3103997 TI - Proposed drug-drug cost effectiveness methodology. AB - The advent of prospective reimbursement in hospitals has forced hospital administrators, pharmacy directors, and pharmacy and therapeutic committees to carefully compare the cost and benefits of similar drugs. Accomplishing this task is difficult. This paper reviews the literature on drug-drug cost effectiveness procedures and outlines a methodology that might be used to contrast and compare two drugs with similar therapeutic outcomes. The data to conduct this analysis can be obtained from published articles on clinical studies and company sources and entered into a microcomputer electronic spreadsheet. The study discusses the implications and use of cost effectiveness analysis to evaluate drugs by hospital formulary committees. PMID- 3103998 TI - Reimbursement for inpatient nutrition services and home health-care services. PMID- 3103999 TI - Theophylline clearance increase from increased amino acid in a CPN regimen. PMID- 3104000 TI - [Diphtheria, an imported disease]. AB - A comparative analysis of 4256 persons living in the Federal Republic of Germany and 4751 applicants for asylum in the FRG allows the conclusion that in the FRG diphtheria is caused by imported toxinogenic strains, originating mostly from developing countries. Since 1975 a total of 109 cases have been observed, 22 ending in death. Such severe cases can be avoided by systematic revaccination even of adults. PMID- 3104001 TI - [Fibrinolytic therapy in ischemic brain infarct]. PMID- 3104002 TI - Epidemiological studies of workers with exposure to tri- and tetrachloroethylenes. PMID- 3104003 TI - Genotoxicity of mycotoxins. AB - Mycotoxins with their diversified structures have been a class of good model compounds, or a good tool, for evaluating the usefulness of short-term genotoxicity tests and for elucidating the mechanism of mutagenicity and carcinogenicity. Despite the limitations of these tests in predicting carcinogenicity, the genotoxicity of mycotoxins as shown by the results of a battery of genotoxicity tests indicates that mycotoxins are indeed a class of significant naturally occurring environmental carcinogens which warrant rigorous regulatory actions. PMID- 3104004 TI - Historical background of studies on environmental chemical carcinogenesis in Japan and recent progress in toxicology of carcinogens. PMID- 3104005 TI - Spontaneous abortions, stillbirths and birth defects in epidemiological search for risk indicators. PMID- 3104006 TI - Drug-induced nephropathy: our recent clinical experience. PMID- 3104007 TI - Histopathology associated with cochlear implants. PMID- 3104008 TI - Structure-activity relationships of selected pyridines. III. Log Kow analysis. AB - Twenty 2- and 3-position derivatives of pyridine (C5H5N) were tested following a short-term static protocol. Biological activity was monitored as population growth of Tetrahymena pyriformis. These data were combined with previously reported data for twenty 4-position derivatives. Structure-activity relationships were examined using Kow as the physicochemical descriptor. These data form three linear models: one for the non-H-polar derivatives and two for the H-polar derivatives. The latter two models are parallel but have no obvious basis for a priori selectivity. HPLC analysis for toxicant persistence shows that only the smaller non-H-polar derivatives have any significant abiotic loss over the duration of the biological testing. PMID- 3104009 TI - Comparative kinetics for bioaccumulation of polychlorinated biphenyls by the polychaete (Capitella capitata) and fish (Mugil cephalus). AB - The bioaccumulation of Aroclors 1242, 1254, and 1260 from sediments by the polychaete (Capitella capitata) and from water by the mullet (Mugil cephalus) was measured in aquarium experiments and followed by clearance investigations. This allowed calculation of the bioaccumulation factor (KB), uptake rate constant (k1), clearance rate constant (k2), and derived half-life (t1/2). The k2 and t1/2 values were of comparable magnitude for each organisms, but k1 values, calculated for polychaetes on the basis of PCB concentrations in whole sediment, were considerably lower, as were the KB values similarly determined. Using the Freundlich equation, an expression was developed for KB assuming that uptake occurred from interstitial water. This expression required the use of empirically developed constants for sedimentary characteristics but gave values for k1 and KB comparable to the values obtained with the fish. PMID- 3104011 TI - Differential effects of estradiol, arachidonic acid, and A23187 on prostaglandin F2 alpha output by epithelial and stromal cells of human endometrium. AB - Primary monolayer cultures of glandular epithelial cells and stromal cells derived from human endometrial curettings release similar amounts of prostaglandin F2 alpha (PGF2 alpha) to the incubation medium, but PGF2 alpha output is significantly increased by estradiol (E2; 10(-8) M) only in epithelial cells. The differential responsiveness to estrogens of these two cell types was further demonstrated in the presence of exogenous arachidonic acid (AA), a PG precursor that markedly elevated PGF2 alpha output by both epithelial and stromal cells. In epithelial cell cultures, the increases in PGF2 alpha output obtained with mixtures of E2 and AA were about 2.5-fold greater than the sum of the increases elicited by E2 or AA alone. In contrast, the effects of AA in stromal cell cultures were not enhanced by E2. Addition of the calcium ionophore A23187 to cultures of epithelial cells resulted in a Ca2+-dependent increase in PGF2 alpha output, which could be further augmented by E2 to levels almost twice the sum of those produced by each agonist alone. Unlike its effects on epithelial cells, A23187 did not significantly increase PGF2 alpha levels in stromal cell cultures, regardless of the addition of Ca2+ (1.5 mM) or E2 (10(-8)M) to the culture medium. These results suggest that the epithelia and not the stroma are the primary targets for the effects of E2 on PGF2 alpha output by the endometrium. The synergistic effects of E2 and AA (the substrate for PG synthase) or of E2 and A23187 (a stimulator of phospholipase-mediated release of AA from phospholipid stores) on PGF2 alpha production suggest that estrogens enhance PG production in epithelial cells by elevating PG synthase activity. PMID- 3104010 TI - Germ cell stimulation of Sertoli cell protein phosphorylation. AB - Cultures of Sertoli cells were treated with freshly isolated, intact germ cells to determine if germ cells were capable of influencing Sertoli cell function. By using two-dimensional polyacrylamide gel electrophoresis and autoradiography, germ cells were found to increase several-fold the incorporation of [32P]orthophosphate into two phosphoproteins (which we term germ cell-dependent phosphoproteins 1 and 2 or GC1 and GC2) of Sertoli cells. Increased phosphorylation of GC1 and GC2 was rapid, germ cell dose dependent, and calcium dependent. The increased phosphorylation of GC1 appears to involve calmodulin dependent protein kinase, while phosphorylation of GC2 appears to involve the activation of calcium/phospholipid-dependent protein kinase (protein kinase C). Medium conditioned by germ cells was capable of eliciting the same response in Sertoli cells. Germ cells had no effect on the phosphorylation of proteins in Chinese hamster ovarian cells, but did result in increased phosphorylation of a protein in TR-ST cells, which migrated similarly to GC1 of Sertoli cells. Neither Chinese hamster ovarian nor TR-ST cells had any effect on Sertoli cell protein phosphorylation. These results indicate that germ cells may be directly involved in the local regulation of Sertoli cell function within the seminiferous epithelium. The results further suggest that the mechanism of germ cell-Sertoli cell interaction involves the mobilization of intracellular calcium, activation of Ca2+/calmodulin-dependent protein kinase, and protein kinase C. We infer from these results that germ cell-Sertoli cell interaction may operate via hydrolysis of Sertoli cell membrane phophatidylinositols. PMID- 3104012 TI - Porcine follicular fluid contains both follicle-stimulating hormone agonist and antagonist activities. AB - Several fractions were prepared from porcine follicular fluid, each having FSH receptor binding inhibitory activity. All were soluble in acidic acetone (pH 3.5) and insoluble in ether (pH 10.5), and could be separated on the basis of charge, using anion exchange HPLC. The effect of these fractions on aromatization of androstenedione to estradiol (basal levels or FSH stimulated) was studied in vitro using Sertoli cells from immature rat testes. Agonist activity, defined as the ability to stimulate secretion of estradiol in the absence of FSH, was present in one fraction weakly retained by the anion exchange column but eluted with a linear gradient between 0.2 and 0.5 M acetate, pH 5.0. In addition to agonist activity, this fraction inhibited binding of [125I]human (h) FSH to hFSH antiserum and to receptor. Another fraction with FSH binding inhibitory activity was more strongly retained by the anion exchange HPLC column and was eluted with 1.0 M acetate, pH 3.0. This fraction demonstrated antagonist activity, as defined by its ability to inhibit FSH-stimulated, but not basal, conversion of androstenedione to estradiol in vitro. Although it inhibited [125I]hFSH binding to receptor, no immunoreactivity could be demonstrated in this fraction. These observations demonstrate that inhibition of [125I]hFSH binding to receptor can reflect either agonist or antagonist activity, and that the latter activities are present in separate and distinct fractions derived from porcine follicular fluid. PMID- 3104013 TI - Hormonal control of pubertal spermatogenesis. AB - The spermatogenic process of normal rats at 20, 32, and 44 days of age was characterized. Variations in numbers of degenerating and abnormal cells were noted during the cycle in most age groups, indicating a stage-related vulnerability of these cells. The most advanced cell types that were seen at a particular age were frequently abnormal or degenerating. When the numbers of viable cells available to degenerate were considered, the degeneration rate in normal pubertal animals was about 15, 10, and 2 times greater in 20-, 32-, and 44 day-old animals, respectively, than in 75-day-old animals. In 32-day-old rats, neither hypophysectomy nor hypophysectomy and subsequent hormone supplementation resulted in an alteration in the qualitative pattern of germ cell degeneration during the spermatogenic cycle compared with that in the normal animal; however, the treatments did alter the quantitative response of cellular degeneration. Three days posthypophysectomy there was a marked increase in the numbers of total degenerating germ cells. FSH (60 micrograms) given twice daily (as were all hormones) reduced the numbers of degenerating cells significantly, as did LH (13 micrograms). Low dose LH (0.3 micrograms), representing the approximate contaminating dose of LH in the 60-micrograms FSH preparation, and low dose FSH (30 micrograms) did not elicit a response significantly different from that to hypophysectomy alone. LH (13 micrograms) plus FSH (60 micrograms) reduced the levels of degenerating cells such that there was no significant difference from levels in intact 32-day-old rats. The data indicated, for the cell types studied, a lack of specificity of various hormones or hormone combinations in the survival of specific germ cell types. It emphasizes the importance of FSH in pubertal spermatogenesis as well as the synergistic actions of LH and FSH. PMID- 3104014 TI - Follicle-stimulating hormone and somatomedin-C stimulate inhibin production by rat granulosa cells in vitro. AB - The direct effect of somatomedin-C (Sm-C) and FSH on inhibin production by rat granulosa cells in vitro has been examined. FSH stimulated accumulation of inhibin in culture media in a dose-dependent manner with maximal stimulation (6 fold) being observed at a dose of 300 ng FSH/ml. Addition of Sm-C (30 ng/ml) either alone or in the presence of FSH (3-300 ng/ml) increased inhibin production (up to 5-fold). Sm-C alone was effective over the physiological dose range of 3 100 ng/ml. Concomitant addition of FSH (100 ng/ml) and Sm-C (3-100 ng/ml) resulted in a significant increase in inhibin production at all doses of Sm-C. The dose-dependent effects of FSH and Sm-C were also time dependent with a synergistic effect apparent after 48 h of culture. The Sm-C induced FSH inhibitory activity of granulosa cell culture media was confirmed as authentic inhibin by the demonstration of a dose-dependent neutralization of this activity by a monoclonal antibody raised against purified bovine inhibin. The data indicate a direct role for both FSH and Sm-C in ovarian inhibin production and provide additional evidence for an autocrine-paracrine role for Sm-C in granulosa cell differentiation. PMID- 3104015 TI - The growth hormone (GH)-releasing hormone (GHRH)-GH-somatomedin axis: evidence for rapid inhibition of GHRH-elicited GH release by insulin-like growth factors I and II. AB - Hypothalamic-pituitary-end-organ axes are frequently controlled by long loop negative feedback homeostatic mechanisms. Insulin-like growth factor I (IGF-I), IGF-II, and insulin receptors have recently been described in normal and neoplastic rat and acromegalic human pituitary cells, a finding which suggests the possibility that somatomedins might exert feedback at the level of the anterior pituitary. To study the kinetics of this feedback response, we used perifused dispersed rat anterior pituitary cells to learn if somatomedins or insulin could inhibit GH-releasing hormone (GHRH)-stimulated GH secretion. Cells were exposed to hourly boluses of 1 nM GHRH with or without varying doses of IGF or insulin. IGF-I inhibited GHRH-elicited GH release with an IC50 of 6.5 nM; maximal inhibition (approximately 67%) was achieved with 10 nM IGF-I. IGF-II was a less potent hormone, with 10 nM inhibiting about 30% of GHRH-stimulated GH release. Slight inhibition of stimulated GH release (less than 15%) was seen when cells were treated with insulin, but only when doses of insulin of 10 nM or more were used. In conclusion, nanomolar concentrations of IGF-I and IGF-II inhibited GHRH-elicited GH release from perifused rat pituitary cells in a dose-dependent manner; and insulin was not an effective inhibitor of stimulated GH release at physiological peptide concentrations. In conjunction with our previous findings that the concentrations of IGF-I and IGF-II receptors greatly exceed that of insulin receptors on normal rat pituitary cells, we hypothesize that the GH inhibiting action of high dose insulin is mediated through an IGF receptor. PMID- 3104016 TI - Inhibin: measurement and role in the immature female rat. AB - The possible physiological significance of endogenous inhibin has been evaluated in the female rat during sexual maturation. Plasma inhibin levels measured by a specific RIA were very low, but detectable at 5 days of age, then progressively increased until day 17, when they showed an abrupt rise. This rise was concurrent with a dramatic fall in plasma FSH levels. At day 30, inhibin values were not significantly (P greater than 0.05) different from those of adult females. The immunoneutralization of endogenous inhibin had no statistically significant (P greater than 0.05) effect on plasma FSH levels in 10-day-old immature female rats, but markedly (P less than 0.01) increased them at day 20 and 30. These results suggest that endogenous inhibin plays a physiological role in modulating FSH secretion from day 20 of age in the female rat. PMID- 3104017 TI - The acute stimulatory effect of estrogen on gonadotropin release in gonadotropin releasing hormone-primed women. AB - In order to prove the acute stimulatory effects of estrogen on pituitary gonadotropin release, we have performed the present experiments in 8 women with a hypergonadotropic state due to surgical castration or primary ovarian failure. They received gonadotropin releasing hormone (Gn-RH) for 12-21 h at the constant rate of 20 micrograms/h. In 5 of the women, estradiol-17 beta was concomitantly administered at the rate of 20 micrograms/h from 6 h after the start of Gn-RH infusion. Blood samples were collected frequently throughout the experiments for the analysis of LH, FSH and estradiol. In response to the sole stimulation of Gn RH, remarkable and prompt rises in LH (313.5%), but to a lesser degree in FSH (194.2%), were observed within the initial 3 h, and their high levels were maintained throughout the experimental period. However, the additional administration of estradiol brought on a further sudden rise in both gonadotropins levels: 178.3% for LH and 163.5% for FSH within 2 h. These high levels were sustained during estradiol infusions. In 2 of them, blood samples were obtained for several hours after cessation of estradiol infusion. The circulating gonadotropin level dropped precipitously close to the baseline level within 3 h after estradiol infusions. Our data indicate that estrogen has an acute and strong augmentative effect on Gn-RH induced gonadotropin release in addition to its conventional negative and positive feedback effects. PMID- 3104018 TI - Inhibitory activity of a low molecular weight substance extracted from porcine small follicular fluid on estradiol and progesterone secretions by rat granulosa cells in vitro and by rat ovaries in vivo. AB - Follicular fluid from small porcine follicles was filtrated through an Amicon XM 50 membrane to obtain a filtrate less than 50,000 MW. The filtrate was eluted through a Sephadex G-25 column (1.5 X 70 cm) using 0.01 N CH3COOH, pH 4.0, as elution buffer, and divided to five fractions. To test the inhibitory activity of these fractions on the in vitro estradiol and progesterone secretion, each fraction was added into a rat granulosa cell culture with FSH and testosterone in the medium. Two of five fractions exerted a significant inhibitory activity on the estradiol and progesterone secretions by the granulosa cells. They were in a range of low molecular weight fractions (MW 1,000-3,000) on the elution profile. Whether the in vitro active fractions are capable of inhibiting the in vivo estradiol and progesterone secretions by the ovary was assessed using the hypophysectomized DES-treated immature rat with hMG stimulation and the testosterone-treated immature rat with PMSG stimulation. The administration of the fractions to the former animal significantly suppressed the increases due to gonadotropin in the ovarian and serum estradiol concentrations. The administration of the fractions to the latter animal significantly suppressed the increases due to gonadotropin in the estradiol and progesterone concentrations of the ovary and serum. These results suggest that a low molecular weight substance from porcine small follicular fluid is capable of inhibiting the estradiol and progesterone biosyntheses in the follicle of the rat ovary. PMID- 3104019 TI - Immunological study of ovarian inhibin. AB - Antisera to purified porcine follicular fluid inhibin of 32 K protein (pFF 32 K inhibin) were raised in rabbits. Increasing doses of an antiserum with high titer could neutralize the maximal suppression of FSH secretion caused by 10 ng of pFF 32 K inhibin from rat anterior pituitary cells in culture. A radioimmunoassay was developed using the antiserum and 125I-labelled pFF 32 K inhibin. Specificity of the antiserum was examined by comparing immunological and biological potencies of various inhibin preparations. Cross-reactivity tests revealed that the antiserum almost recognizes rat ovarian inhibin preparations. The antiserum also recognizes purified bovine follicular fluid inhibin of 32 K protein (bFF 32 K inhibin), but with a cross-reactivity of approximately 20%. Cross-reactivity of human follicular fluid to the antiserum was less than 10%. The antiserum also recognizes inhibin forms of higher molecular weights, 100 K, 80 K, and 55 K proteins, which have previously been identified by gel filtration or SDS-PAGE of crude pFF inhibin preparations under protein-dissociation conditions, indicating that these inhibin forms have common or closely related immunodetermining sites. PMID- 3104020 TI - Effect of thyroxine-binding globulin (TBG) on thyroxine (T4) uptake by human peripheral mononuclear cells: evidence of TBG-dependent uptake of T4. AB - The effect of sialylated TBG and desialylated TBG on thyroxine (T4) uptake by human peripheral mononuclear cells was investigated in vitro. [125I]-T4 uptake was observed when the cells were incubated with free [125I]-T4. The uptake was inhibited in a concentration dependent manner when TBG was added. During the incubation, [125I]-T4 binding to TBG was observed. [125I]-T4 incorporation into cells was also observed when the cells were incubated with [125I]-T4-sialylated TBG or with [125I]-T4-desialylated TBG complex. The uptake was related to the temperature and length of time of the incubation. The amount of [125I]-T4 incorporated into the cells incubated with [125I]-T4-sialylated TBG was greater than that into the cells incubated with [125I]-T4-desialylated TBG during the early 0-20 min. incubation, whereas the amount of [125I]-T4 incorporated into the cells incubated with [125I]-T4-desialylated TBG became greater than that into the cells incubated with [125I]-T4-sialylated TBG after 20 min. of incubation. Pretreatment of the cells with methylamine blocked [125I]-T4 uptake in both cases, i.e. incubated with [125I]-T4-sialylated TBG and incubated with [125I]-T4 desialylated TBG. The results suggest that TBG plays a role not only as a carrier protein for T4 in circulation but also as a protein which can transport T4 from the extracellular into the intracellular space, so that the mechanism of T4 transport mediated by desialylated TBG is different from that mediated by sialylated TBG, and that the T4 transport system in both cases, mediated by sialylated TBG and by desialylated TBG, may be related to the internalization of T4-TBG-TBG receptor complex or of T4-T4 receptor complex if TBG receptors are present in the outer surface of the cell membrane. PMID- 3104021 TI - Thyroid hormone response to thyrotrophin releasing hormone (TRH) in the sex linked dwarf chicken. AB - The effect of an injection of thyrotrophin releasing hormone (TRH) on plasma levels of thyroid hormones was studied in dwarf and normal Rhode Island Red chickens with similar genotypes other than for the sex-linked dwarf gene dw. The sex-linked dwarf chickens had different plasma iodothyronine levels from control normal chickens: high thyroxine (T4), low triiodothyronine (T3) and similar reverse T3 (rT3) levels. The injection of TRH (10 micrograms/kg) in 5-day- and 5 week-old normal chickens increased the plasma T4 within 30 min without a significant increase in T3, whereas the injection of TRH in 11-and 26-week-old normal chickens increased plasma T3 60 min later. In dwarfs the response of T4 to TRH was the same as that in normals but no increased T3 response was observed. The plasma level of rT3 was not influenced by the TRH injection in either strain. These results suggest that although in the sex-linked dwarfs thyroidal response to exogenous TRH is similar to that of normals, the dwarf gene dw inhibits the conversion of T4 to T3 in peripheral tissues without any inhibitory effect on rT3 production. PMID- 3104023 TI - Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms. AB - The exposure of cultured rat hepatocytes to mono(2-ethylhexyl)phthalate (MEHP) for 72 hr resulted in marked induction of peroxisomal enzyme activity (beta oxidation; cyanide-insensitive palmitoyl CoA oxidase) and concomitant increases in the number of peroxisomes. Similar treatment of cultured guinea pig, marmoset, or human hepatocytes revealed little or no effect of MEHP. In order to eliminate possible confounding influences of biotransformation, the proximate peroxisome proliferator(s) derived from MEHP have been identified. Using cultured hepatocytes these agents were found to be metabolite VI [mono(2-ethyl-5-oxohexyl) phthalate] and metabolite IX [mono(2-ethyl-5-hydroxyhexyl) phthalate]. The addition of these "active" metabolites to cultured guinea pig, marmoset, or human hepatocytes again revealed little effect upon peroxisomes or related enzyme activities (peroxisomal beta-oxidation or microsomal lauric acid hydroxylation). These studies demonstrate a marked species difference in the response of hepatocytes to MEHP-elicited peroxisome proliferation. Preliminary studies have also suggested that peroxisome proliferation due to MEHP may be due to an initial biochemical lesion of fatty acid metabolism. PMID- 3104024 TI - Evaluation of potential health effects associated with serum polychlorinated biphenyl levels. AB - In late 1983, we conducted a cross-sectional epidemiologic study to evaluate persons at risk of exposure to three chemical waste sites by comparing clinical disease end points and clinical chemistry parameters with serum polychlorinated biphenyls (PCB) levels. A total of 106 individuals participated in the study. The only statistically significant finding in regard to self-reported, physician diagnosed health problems was a dose-response relationship between serum PCB levels and the occurrence of high blood pressure; however, this association failed to achieve statistical significance (p = 0.08) when we controlled for possible confounding effects of both age and smoking. Serum triglyceride and cholesterol levels were also higher in the group with elevated serum PCBs; additionally, there were isolated statistically significant correlations of serum aspartate aminotransferase (SGOT) with serum lipid fraction-adjusted PCB level (r = -0.21) and serum albumin (r = -0.24) and total bilirubin (r = 0.30) with serum PCB level. Although the ranges of serum levels reported herein from exposures to PCBs in the general environment are lower than those that have been associated with acute symptoms or illness in other studies, whether these levels are associated with long-term health risks is not known. Associations of such chronic, low-dose exposures with observable health effects as suggested by this study must be evaluated further before any final conclusions can be drawn. PMID- 3104022 TI - Species differences in pharmacokinetics and drug teratogenesis. AB - Interspecies differences in regard to the teratogenicity of drugs can be the result of differing pharmacokinetic processes that determine the crucial concentration-time relationships in the embryo. Maternal absorption, as well as distribution, of the drugs does not usually show great species differences. The first-pass effect after oral application is often more pronounced in animals than man (e.g., valproic acid, 13-cis-retinoic acid), although in some cases the reverse was found (e.g., hydrolysis of valpromide). Existing differences can be adjusted by appropriate choice of the administration route and measurements of drug levels. Many variables determine the placental transfer of drugs: developmental stage, type of placenta, properties of the drug. Even closely related drugs (e.g., retinoids) may differ greatly in regard to placental transfer. Maternal protein binding is an important determinant of placental transfer, since only the free concentration in maternal plasma can equilibrate with the embryo during organogenesis; this parameter differs greatly across species (e.g., valproic acid: five times higher free fractions in mouse and hamster than in monkey and man). The metabolic pattern has not yet been demonstrated to be a major cause of species differences, although recent evidence on phenytoin and thalidomide support the hypothesis that some species differences can be the result of differing activation/deactivation pathways. Laboratory animals usually have a much higher rate of drug elimination than man. Drastic drug level fluctuations are therefore present during teratogenicity testing in animals, but not to the same degree in human therapy. It must, therefore, be investigated if peak concentrations (such as for valproic acid and possibly caffeine) or the area under the concentration-time curve (AUC) (such as for cyclophosphamide and possibly retinoids) correlate with the teratogenic response. Only then is a rational and scientific basis for interspecies comparison possible. It is concluded that the prediction of the human response based on animal studies can be improved by consideration of the appropriate pharmacokinetic determinants. PMID- 3104026 TI - Improving adherence to physical activity. AB - Two studies tested the efficacy of Marlatt and Gordon's relapse-prevention approach in increasing attendance during an exercise program (short-term adherence) and continuation of exercise activities for 12 weeks following termination of the formal program (longer term adherence). Participants in both studies were registrants in 10-week exercise groups (jogging, aerobic dance, and pre-ski training) sponsored by the Universite de Montreal Sports Centre. The intervention, designed to increase awareness of obstacles to exercise and to develop appropriate techniques for coping with them, was delivered by group leaders within the context of the regular program. Results of both studies indicate a small but consistent superiority of adherence in the experimental condition compared to the control condition. The low cost of this intervention, however, makes even small gains cost effective. Possible methods for strengthening the treatment effect are discussed. PMID- 3104025 TI - Results of in vivo and in vitro studies for assessing prenatal toxicity. AB - Examples of a combined approach using in vivo as well as in vitro methods for the assessment of prenatal toxicity are presented. The topics discussed include the analysis of the possible embryotoxic potential of valproic acid (VPA), female sex hormones, bis(tri-n-butyltin) oxide (TBTO), and acyclovir and the problem of supplementing in vitro systems with drug-metabolizing activity. PMID- 3104027 TI - Alternative splicing and alternative initiation of translation explain the four forms of the Ia antigen-associated invariant chain. AB - The Ia antigen-associated invariant chain (In) exists in humans as four related polypeptides, p33, p35, p41 and p43, all associated with HLA-class II antigens. As described previously, two of these forms of In chain, p33 and p35, result from the use of two in-phase initiation AUG codons on the unique In p33 mRNA. In addition to cDNA clones derived from In p33 mRNA, we have isolated a new cDNA clone, called p41-1, which differs from p33-1 by an additional segment in the coding region. The DNA sequence encoding the segment unique to p41-1 was identified in the genomic sequence in the intron between exon 6 and 7, and we refer to it as exon 6b. Cells transfected with a full length p41 cDNA clone in an expression vector synthesize the two larger forms of the In chain, p41 and p43. We propose that the larger mRNA, encoding p41, results from alternative splicing of exon 6b, and that p41 and p43 result from the use of the two functional initiation AUG codons identified in p33 mRNA. Alternative splicing, together with alternative initiation of translation, allows therefore the synthesis of four related In chain polypeptides from a single gene. PMID- 3104028 TI - Selective radiolabelling and identification of a strong nucleosome binding site on the globular domain of histone H5. AB - We describe a chemical investigation of the nucleosome binding site(s) on histone H5. Selective radiolabelling by reductive methylation has led to the identification of lysine residues in H5 that are protected by its association with chromatin. The most strongly protected lysine is Lys-85 which occurs in the globular domain, in a region that is highly conserved between H5 and H1, and in H1 variants, and which probably constitutes a strong binding site for DNA where it enters and leaves the nucleosome. Lysines in the amino-terminal and lysine rich carboxy-terminal tails are only weakly protected against chemical modification, suggesting a different mode of interaction with DNA. PMID- 3104029 TI - Two Drosophila chorion genes terminate transcription in discrete regions near their poly(A) sites. AB - We have examined transcription termination of two closely linked Drosophila melanogaster chorion genes, s36-1 and s38-1, using the electron microscope. Our method is unusual and is independent of in vitro nuclear run-on transcription. By measuring transcription unit lengths in chromatin spreads, we can localize efficient termination sites to a region of approximately 210 bp for s36-1 and approximately 365 bp for s38-1. The center of this region is approximately 105 nucleotides downstream of the poly(A) site for the s36-1 gene, and approximately 400 nucleotides downstream for the s38-1 gene. Thus, these two Drosophila chorion genes terminate more closely to their poly(A) addition sites and in a shorter region than many other polyadenylated genes examined to date. PMID- 3104030 TI - E. coli ribosomes with a C912 to U base change in the 16S rRNA are streptomycin resistant. AB - Resistance to streptomycin (Sm) of Euglena gracilis chloroplasts can be due to a single C to T transition of the 16S rRNA gene in an invariant position which is equivalent to C912 of the Escherichia coli 16S rRNA. Since Euglena chloroplasts cannot be transformed we introduced, by site-directed mutagenesis, a C912 to T transition in the cloned rrnB operon (pKK3535) of E. coli and used this new construct (pEM109) in transformation experiments. Transformed E. coli cells were selected for Sm resistance by colony plating and stepwise increase of Sm up to 25 micrograms/ml of culture medium. Several Sm-resistant colonies were obtained. Ribosomes were isolated from pEM109-transformed Sm-resistant and pKK3535 transformed Sm-sensitive cells. The ribosomes were assayed in vitro for Sm induced misreading of poly(U) mRNA. We isolated 16S rRNA and sequenced the crucial RNA region by reverse transcription. The results clearly show that ribosomes from Sm-resistant cells correctly read the poly(U) mRNA in the presence of 25 micrograms Sm/ml of reaction mixture and the 16S rRNA contains the C912 to U transition. We conclude that C912 is involved in a translation step(s) which is (are) sensitive to streptomycin. PMID- 3104031 TI - Requirements for the formation of plasmid-transducing particles of Bacillus subtilis bacteriophage SPP1. AB - We had previously proposed that the production of concatemeric plasmid DNA in plasmid-transducing SPP1 particles is a consequence of phage-directed rolling circle-type replication of plasmid DNA. The production of such DNA was greatly enhanced when DNA/DNA homology was provided between phage and plasmid DNAs (facilitation of transduction). Here we present evidence that synthesis of concatemeric plasmid DNA can proceed after phage infection under conditions non permissive for plasmid replication. We also propose that the naturally occurring homology between plasmid and phage is sufficient to account for the frequency of transduction observed in the absence of facilitating homology. Homology of greater than 47 bp gives the maximal facilitation of plasmid transduction. Recombination is not an essential part in the synthesis of concatemeric plasmid DNA. PMID- 3104032 TI - Alpha-lactalbumin and related proteins: a versatile gene family with an interesting parentage. PMID- 3104033 TI - Maximal oxygen uptake in Danish adolescents 16-19 years of age. AB - A random sample of schoolchildren, 119 boys and 153 girls, was tested in the fall of 1983. The data presented here are anthropometric data (height, weight, fat % and vital capacity) and oxygen uptake directly measured on a bicycle ergometer. The mean height and weight for boys were 179.1 cm and 67.7 kg, and those for girls were 168.0 cm and 59.6 kg. The mean fat content was 9.1% for boys and 19.1% for girls, and their mean vital capacities were 4.91 and 3.61 respectively. The boys had a high maximal oxygen uptake (51.7 ml X kg-1 X min-1) showing no reduction over the age span studied. The girls' maximal oxygen uptake was lower (overall mean 40.0 ml X kg-1 X min-1) with a small reduction from 16 to 19 years of age. When comparing maximal oxygen uptake per kg lean body mass in the two sexes, the boys had 18.4% higher values than the girls, indicating that girls of this age have the lower fitness level. The results of maximal aerobic power measurement in the boys compare well with findings from other investigations using direct measurements, indicating that the fitness of teenage boys is kept at a high level. Comparable data from various countries for girls show different pictures, but it appears that in general they have a low fitness level. PMID- 3104034 TI - Cardiac effects of short term arm crank training in paraplegics: echocardiographic evidence. AB - The cardiac responses of male paraplegics to upper-body endurance training have been studied by M-mode echocardiography and CO2-rebreathing determination of cardiac output. Data for nine exercised subjects are compared with 5 controls. After 16 weeks of arm ergometer exercise, heart rates of trained individuals were 9 bt X min-1 lower during isometric handgrip effort (30% of MVC for 3 min), with a substantial decrease of rate pressure product (20%; p less than 0.05). In contrast (possibly because of greater anticipation) the control subjects developed a larger rate-pressure product with repetition of the standard isometric effort. Despite a significant increase of VO2 peak (19% and 31% after 8 and 16 weeks, respectively; p less than 0.05), echocardiographic LV mass, dimensions and indices of LV performance were unchanged by training, either at rest or during the isometric handgrip. Stroke volumes were significantly increased by 12-16% after training, both in isometric and in rhythmic work; at the highest intensity of arm ergometry, there was also a suggestion of increased cardiac output. We conclude that a short period of arm training is insufficient to induce cardiac hypertrophy, an increase of stroke volume with a decreased rate pressure product but no change in echocardiographic indices of LV performance implies an improved myocardial efficiency. Possible explanations are a greater strength of the trained arms, and some increase of pre-loading (due to an increase of venous tone and more effective operation of the muscle pump after training). PMID- 3104035 TI - Amino acid sequence of the serine active-site region of the medium-chain S-acyl fatty acid synthetase thioester hydrolase from rat mammary gland. AB - Medium-chain S-acyl fatty acid synthetase thioester hydrolase (thioesterase II), a discrete monomeric enzyme of 29 kDa, regulates the product specificity of the de novo lipogenic systems in certain specialized mammalian and avian tissues, such as mammary and uropygial glands. The amino acid sequence of a 57-residue region containing the active site of the rat mammary gland enzyme has been established by a combination of amino acid and cDNA sequencing. Thioesterase II was radiolabeled with the serine esterase inhibitor [1,3-14C]diisopropyl fluorophosphate and digested sequentially with cyanogen bromide, Staphylococcus aureus V8 protease and trypsin. A radiolabeled tryptic peptide was isolated and sequenced by automated Edman degradation and the location of the active-site residue established. The amino acid sequence was confirmed by sequencing an overlapping, unlabeled peptide, obtained by V8 digestion of the whole enzyme, and by dideoxynucleotide sequencing of a thioesterase II cDNA clone isolated from a lambda gt11 expression library. The active center contains the motif Gly-Xaa-Ser Xaa-Gly, characteristic of the serine esterase family of enzymes. A seven-residue region around the essential serine of the rat mammary thioesterase II, Phe-Gly Met-Ser-Phe-Gly-Ser, is completely homologous with a region of the mallard uropygial thioesterase, recently analyzed by cDNA sequencing, indicating that this is likely to be the active site of the avian enzyme. Overall homology between the mammalian and avian enzymes for the 57-amino-acid residue region is 47% and suggests that the two enzymes may share a common evolutionary origin. PMID- 3104036 TI - Characterization of six toxins from the venom of the Moroccan scorpion Buthus occitanus mardochei. AB - When the venom of the Moroccan scorpion Buthus occitanus mardochei was submitted to a combination of several chromatographic steps (including gel-filtration and ion-exchange chromatographies), seven proteins were obtained, six being lethal to mice. These proteins have been characterized by their chemical, immunological and toxic properties. The amino acid sequence (66 residues) of Bom III, the most noteworthy toxin of the venom as for its amino acid composition, is proposed following automatic sequencing of the reduced and S-methylated protein and of chymotryptic peptides. It was obvious that this sequence is somewhat different from those of toxins belonging to the same structural and immunological group (Bom III was found to be immunologically related to Buthus occitanus tunetanus toxins I and II which both share with it 56% of homology. Furthermore, Bom III was found to be unable to compete (as does Bot I) with toxin II of Androctonus australis Hector (an alpha-type toxin) for neurotoxin binding site 3 on the sodium channel of rat brain synaptosomes. Bom III was also unable to compete with toxin II of Centruroides suffusus suffusus (a beta-type toxin) to neurotoxin binding site 4 of the same channel. PMID- 3104037 TI - Characterization of an artificial bifunctional enzyme, beta galactosidase/galactokinase, prepared by gene fusion. AB - An artificial bifunctional enzyme, beta-galactosidase/galactokinase, has been prepared by gene fusion. The hybrid protein catalyzes the hydrolysis of lactose followed by phosphorylation of galactose. The protein has been purified using DEAE-Sephacel chromatography and gel filtration on Sephacryl S-400 Superfine. The configuration of the hybrid protein is mainly tetrameric but also higher aggregates can be detected. The monomer Mr is 160,000 as judged from sodium dodecyl sulfate/polyacrylamide gel electrophoresis and the native Mr has been calculated to be 600,000-650,000 from gel filtration experiments. beta Galactosidase/galactokinase has different thermostability curves, pH/activity profiles and Km values as compared with the native enzymes. By using a third enzyme, galactose dehydrogenase, which competes with galactokinase for the galactose formed by beta-galactosidase, substrate channeling can be detected. This proximity effect becomes even more pronounced in an assay mixture containing poly(ethylene glycol). PMID- 3104038 TI - Chemical modification of arginine residues in p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens: a kinetic and fluorescence study. AB - The flavoprotein p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens was modified by several arginine-specific reagents. Modifications by 2,3-butanedione led to the loss of activity of the enzyme, but the binding of p-hydroxybenzoate and NADPH to the enzyme was little or not at all affected. However the formation of the enzyme-substrate complex of the modified enzyme was accompanied by an increase of the fluorescence of protein-bound FAD, in contrast to that of native enzyme which leads to quenching of the fluorescence. Enzyme modified by phenylglyoxal did not bind p-hydroxybenzoate nor NADPH. Quantification and protection experiments showed that two arginine residues are essential and a model is described which accounts for the results. Modification by 4-hydroxy-3 nitrophenylglyoxal reduced the affinity of the enzyme for the substrate and NADPH. The ligands offered no protection against inactivation. From this it is concluded that one arginine residue is essential at some stage of the catalysis. This residue is not associated with the substrate- or NADPH-binding site of the enzyme. Time-resolved fluorescence studies showed that the average fluorescence lifetime and the mobility of protein-bound FAD are affected by modification of the enzyme. PMID- 3104040 TI - Somatic antigens of Pseudomonas aeruginosa. The structure of the O-specific polysaccharide chain of the lipopolysaccharide from P. aeruginosa O13 (Lanyi). AB - The O-specific polysaccharide, obtained on mild acid degradation of lipopolysaccharide of Pseudomonas aeruginosa O13 (Lanyi classification), is built up of trisaccharide repeating units involving 2-acetamidino-2,6-dideoxy-D-glucose (N-acetyl-D-quinovosamine, D-QuiNAc), 2-acetamidino-2,6-dideoxy-L-galactose (L fucosacetamidine, L-FucAm), and a new sialic-acid-like sugar, 5,7-diacetamido 3,5,7,9-tetradeoxy-D-glycero-L-galacto-nonuloso n ic acid (Sug), and thus contains simultaneously both acidic and basic functions. Cleavage of the polysaccharide with hydrogen fluoride in methanol revealed the high stability of the glycosidic linkage of the ulosonic acid and afforded methyl glycosides of a disaccharide and a trisaccharide. The structures of the new ulosonic acid and acetamidino group were established by analysing the oligosaccharide fragments by 1H, 13C nuclear magnetic resonance spectrometry, as well as on the basis of their chemical conversions: alkaline hydrolysis of the acetamidino group into acetamido group, reductive deamination with lithium borohydride into the ethylamino group and acetylation with acetic anhydride in pyridine accompanied by intramolecular acylation of the acetamidino function by the ulosonic acid to form a six-membered lactam ring. Identification of the oligosaccharide fragments and comparative analysis of the 13C nuclear magnetic resonance spectra of the oligosaccharides and polysaccharide revealed the following structure of the repeating unit: --- 3)D-QuiNAcp(alpha 1----3)Sugp(alpha 2----3)L-FucAmp(alpha 1----. PMID- 3104039 TI - CO2 is the inorganic carbon substrate of NADP malic enzymes from Zea mays and from wheat germ. AB - NADP malic enzyme (EC 1.1.1.40) was extracted and partially purified from the green leaves of Zea mays var. Felix and from wheat germ. The active inorganic carbon species for both enzymes was, in contrast to an earlier report, CO2 not HCO3-. The apparent Km, CO2 for the maize enzyme was 1.2 mM and the apparent Km, CO2 for the wheat germ preparation was 4.2 mM under conditions of substrate saturation, pH 7.3 and 17 degrees C. These observations support the views that CO2, rather than HCO3- as has been suggested, is produced in bundle-sheath chloroplasts and that the reaction mechanism catalysed by plant cytosolic and chloroplastic NADP malic enzymes is similar to that proposed for avian NADP malic enzymes. PMID- 3104041 TI - Somatic antigens of Pseudomonas aeruginosa. The structure of O-specific polysaccharide chains of the lipopolysaccharides from P. aeruginosa O5 (Lanyi) and immunotype 6 (Fisher). AB - Lipopolysaccharides were isolated from dry bacterial cells of Pseudomonas aeruginosa O5a,b,c, O5a,b,d, O5a,d (Lanyi classification) and immunotype 6 (Fisher classification) by the Westphal procedure. Their polysaccharide chains were built up of trisaccharide repeating units containing D-xylose, 2-acetamido 2,6-dideoxy-D-galactose and a new sialic acid-like sugar, the di-N-acyl derivative of 5,7-diamino-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulosonic (pseudaminic) acid. Formyl, acetyl and (R)-3-hydroxybutyryl groups were identified as the N-acyl substituents of the last monosaccharide; O5a,b,c and O5a,b,d lipopolysaccharides also contained O-acetyl groups. The glycosidic linkage of pseudaminic acid was extremely labile towards acids, and mild acid degradation of the lipopolysaccharides produced, instead of the O-specific polysaccharides, their trisaccharide fragments with pseudaminic acid at the reducing terminus. Similar degradation of immunotype 6 lipopolysaccharides, followed by oxidation with sodium metaperiodate, resulted in a disaccharide fragment due to destruction of xylose. In contrast the glycosidic linkage of pseudaminic acid proved to be more stable towards treatment with hydrogen fluoride than those of xylose and N-acetylfucosamine. As a result, solvolysis of immunotype 6 lipopolysaccharide with hydrogen fluoride in methanol gave methyl glycosides of a disaccharide and a trisaccharide with pseudaminic acid at the non reducing terminus. Mild acid hydrolysis of these oligosides afforded free 5-N acetyl-7-N-formylpseudaminic acid, which was identified by the 1H ande 13C nuclear magnetic resonance data, as well as by the mass spectrum of the corresponding fully methylated aldonic acid. As a result of the identification of all oligosaccharides obtained and comparative analysis of the 13C nuclear magnetic resonance spectra of the oligosaccharides and lipopolysaccharides the following structures were established for the repeating units of the polysaccharide chains of the lipopolysaccharides: (Formula: see text) where D-Xyl = D-xylose, D-FucNAc = 2-acetamido-2,6-dideoxy-D-galactose, Pse5N7NFm = 5-amino 3,5,7,9-tetradeoxy-7-formamido-L-glycero-L-manno-nonulosonic+ ++ acid (7-N formylpseudaminic acid). All the polysaccharides have an identical carbohydrate skeleton and differ from each other by the acyl substituent at N-5 of pseudaminic acid [acetyl or (R)-3-hydroxybutyryl group] or by the presence or absence of the O-acetyl group at position 4 of N-acetylfucosamine. The data obtained account properly for the O specificity of the studied P. aeruginosa strains. PMID- 3104042 TI - Activation of mercuric reductase by the substrate NADPH. AB - Preincubation of the oxidized form of the flavoenzyme mercuric reductase with the reducing substrate, NADPH, or with a high concentration of cysteine (30 mM) results in a substantial increase of the catalytic activity as measured in a standard spectrophotometric assay. Also NADH has some activating effect but NADP+ or EDTA have no effect. In the presence of 1 mM cysteine only one equivalent of NADPH per FAD seems to be required for full activation which occurs after an incubation time of about 10 min. Activated mercuric reductase appears to be stable under anaerobic conditions but eventually returns to the original level of activity in the presence of oxygen. The activated state seems to be stabilized by 1 mM cysteine. Activation of mercuric reductase does not seem to be correlated with a change in the number of reactive thiol groups. The chemical nature of the activation process is not yet understood. Stopped-flow studies have shown that the nonactivated enzyme is practically inactive prior to contact with the substrates. The enzyme is gradually activated during the assay. The kinetics of activation of the 'native' enzyme is biphasic but 'clipped' enzyme, lacking an 85 residue N-terminal domain, is activated in a single first-order process. The progress curves obtained with preactivated enzyme are approximately exponential even at saturating concentrations of NADPH (Km = 0.4 microM at 25 degrees C, pH 7.3) and Hg2+ (Km = 3.2 microM in the presence of 1 mM cysteine). The initial rates yield kcat values of about 13 s-1 per FAD molecule (25 degrees C, pH 7.3). We find no evidence for a thiol-dependent change from a rapid to a slow kinetic phase. The shape of the progress curves presumably depends on product inhibition, but NADP+ is not a sufficiently effective inhibitor to explain the effect fully. PMID- 3104043 TI - Time course of long-term placebo therapy effects in angina pectoris. AB - A cohort of thirty-five patients with angina pectoris were followed-up for six months with placebo as the only anti-anginal treatment apart from short-acting nitroglycerin. Only patients with at least five attacks per week were entered into the study. Prior to the study, their average number of attacks per week was 10.3(+/- 0.9) and their average nitroglycerin tablet consumption per week was 10.6(+/- 1.2). After admission into the study, the individual dosage of placebo could be blindly titrated during the first eight weeks. Once an adequate dosage was found, it was continued for 6 months. The primary end-point was predefined success or failure of the placebo treatment. Failure was assessed on the lack of improvement, occurrence of 'side-effects', or need for other anti-anginal treatment. In 27 patients, the placebo treatment was said to be a success (95% confidence limits of the percentage of success: 60-90%). No severe cardiac event occurred (confidence limits: 0-10%). Six patients developed 'side-effects'. The number of attacks per week decreased by 48% (P less than 0.0001) during the titration period (8 weeks) and by 77% during the whole 6 months. Exercise test improved, however, less markedly. PMID- 3104044 TI - Regulation of TSH gene transcription. PMID- 3104045 TI - Differing attitudes of industry and academia towards controlled clinical trials. AB - A consensus conference was held in 1984 on controversial issues concerning controlled clinical trials. Thirty-six individuals working in academic institutions, forty-six in industry and twelve in regulatory authorities participated. Academics accepted and industrial representatives rejected the following: existing regulations cannot cope with the rate at which new treatments develop; drug companies may be reluctant to undertake surveillance programmes because sales will fall if adverse reactions are detected; novel remedies should not be promoted before extensive post-marketing surveillance; third parties should finance trials promising to reduce the costs of illness and trialists should be separated from sponsors in data analysis and interpretation, the investigator owning the data unless stated otherwise. Industrial representatives supported and academics rejected the following: government price control inhibits drug development and a multicentre trial can be justified simply by the wish to speed drug registration. PMID- 3104046 TI - Calcium-binding protein from human small intestine. Purification and characterization of a 10,000 molecular weight protein. AB - A calcium-binding protein (CaBP) was purified from human small intestinal mucosa by ammonium sulphate fractionation, gel filtration and chromatofocusing. Antibodies against CaBP were raised in rabbits and CaBP was then isolated from human intestinal cytosol by a one-step immunoadsorbent procedure. In polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate CaBP migrated as a single band corresponding to a molecular weight of 10,000. The calcium-binding ability of CaBP was demonstrated by increased electrophoretic mobility of CaBP in the presence of EDTA as demonstrated by immunoblotting of agarose gels. CaBP antibody showed no cross reaction with cytosolic proteins of duodenum from rat or pig. The present study suggests that molecular properties and distribution of human intestinal CaBP is comparable to those of intestinal CaBP detected in lower mammalian species. PMID- 3104047 TI - Effects of intra-arterial prostaglandin E1 in patients with peripheral arterial occlusive disease. AB - The effects of intraarterially administered prostaglandin E1 (PGE1) on macrocirculatory, microcirculatory and metabolic parameters in patients with peripheral arterial occlusive disease were studied. Nutritive calf muscle blood flow, as determined with the xenon-clearance technique, and muscle tissue oxygen pressure increased markedly in patients with obliterations of the femoral artery. Transcutaneous PO2 as indicator for cutaneous blood flow increased in prestenotic regions dose-dependently whereas there was a clear poststenotic decrease during the infusion period. High lactate/pyruvate ratios in the femoral vein were significantly decreased by PGE1 treatment. PO2 in the femoral vein increased significantly. Thus, PGE1 has some beneficial effects on muscle circulation in these patients. PMID- 3104048 TI - Angiogenic factor from human term placenta. Purification and partial characterization. AB - Angiogenic and growth promoting factors from human amniochorion and placenta at term were released mostly as high molecular weight components (factor-carrier protein higher than 100,000 molecular weight) by extraction with 10% propan-2-ol, distilled water, and 50 mmol l-1 Tris/HCl pH 7.2 containing 50-150 mmol l-1 NaCl. They were isolated from the extracting media by adsorption on DEAE-Sepharose CL6B, a chromatographic agar based anion exchanger, and fractionated by chromatographic permeation on dextran gel Sephacryl S-300 yielding a low molecular weight component (between 400 and 1100 mol wt) with angiogenic and mitogenic capacities. Chromatographic behaviour and physio-chemical characteristics suggest it may be a peptide. Presence of an angiogenic and mitogenic factor in human amniochorion may explain the profuse neovascular formation and increased rate of healing obtained in the treatment of chronic ulcers by application of amniochorionic membranes as biological dressings. Preparation of purified angiogenic factor, on the other hand, opens the possibility of its wider application in the treatment of burns, open wounds and denuded areas in general. PMID- 3104049 TI - Evaluation of low dose anaphylatoxic peptides in the pathogenesis of the adult respiratory distress syndrome (ARDS). Monitoring of early C5a effects in a guinea pig in vivo model after i.v. application. AB - A guinea-pig in vivo model is presented that allows the infusion of purified C5a via a central vein catheter and the monitoring of its effects on granulocytes and platelets, the most important cells in the pathogenesis of several lung disorders, e.g. shock lung. After the infusion of C5a, which was adjusted to a quantity that caused slight and transient alterations of lung physiology, granulocytes disappeared from circulation within 1 min. Simultaneously the granulocyte content of the lung increased about three-fold as judged by histological evaluations. Morphologic destructions were not observed. After the drop a rebound of circulating Polymorpho-nuclear leucocytes (PMN) occurred, which was significantly higher than control values and the appearance of banded cells indicated a mobilization from bone marrow stores. Studies with 51-chromium labelled PMNs revealed that most, but not all, of the granulocytes returned to circulation after transient sequestration. The number of platelets also decreased after C5a infusion, but the rebound was delayed compared with the PMNs and did not exceed control values. The changes in circulating cells, lung histology, and lung physiology are comparable to those occurring during the onset of shock lung and thus strengthen the supposed importance of C5a concerning the pathogenesis of that syndrome. PMID- 3104051 TI - Why do dyspeptic patients prefer one liquid antacid to another? AB - The motives of dyspeptic patients for preferring one treatment over another were examined. In a conventional double-blind study, no difference with respect to the effectiveness of two liquid antacid preparations in symptomatic relief of dyspeptic symptoms was found. In a double-blind randomized self-controlled crossover 'preference study', the two preparations were given in coloured bags. The patients were asked to switch from one type of bag to another until they had a preference. Most patients finally preferred bags displaying the colour which they had initially chosen. The reasons given for preferring one of the drugs were better effectiveness on symptoms, less side effects and better taste. Colour of the bags was not given as a reason. Thus, the patients may prefer drugs on the basis of the external appearance of the wrapping without being aware of the true reason for their choice. PMID- 3104050 TI - Effect of oral prostaglandin E2 on DNA turnover in gastric and intestinal epithelia of the rat. AB - The mucosal incorporation and clearance of a DNA precursor was examined in the rat stomach and intestine following oral treatment with natural prostaglandin E2 (PGE2) or 15(R) 15 methyl prostaglandin E2 (Me PGE2). Control groups received vehicle or pentagastrin. After five days of treatment animals were labelled with methyl-3H-thymidine. Groups of rats were killed at 0.75, 24, 72, 96 and 120 h after labelling. Treatments continued until killed. Mucosal scrapings were analysed for radioactivity and DNA. Morphometric measurements were performed and plasma levels of gastrin and somatostatin determined. PGE2 and its stable analogue produced hyperplasia within one week of treatment, in particular of the gastric antrum and changed the incorporation and clearance of radioactive thymidine from gastric and intestinal epithelia. The most consistent finding was a delayed elimination of thymidine from the mucosa, indicating a slowing of the DNA turnover. The DNA synthesis was differently affected along the gastrointestinal tract, being unchanged or reduced in the stomach and moderately increased in the intestine. Prostaglandin treatment was associated with a three- to ten-fold increase of the gastric acid contents and with elevated plasma levels of gastrin and somatostatin. It is concluded that E2 prostaglandins produce hyperplasia of gastric and intestinal epithelia in the rat by prolonging the cell survival time rather than by increasing new cell production. Hypergastrinemia is not a likely mediator of trophic actions of E2 prostaglandins, which develop despite elevated plasma levels of somatostatin. PMID- 3104052 TI - Pancreatic secretion in the rat influenced by the low molecular weight serine proteinase inhibitor Gabexate mesilate. AB - The effect of intravenous or intragastric administration of the synthetic proteinase inhibitor Gabexate mesilate (GM) on the pancreas of rats was investigated. Infused intravenously at 4 mg kg-1 h-1, GM inhibited both basal or cerulein (0.2 microgram kg-1 h-1)-stimulated pancreatic protein secretion. Intracellular transport and secretion of newly synthesized pancreatic enzymes was not influenced by intravenous infusion of GM. Intragastric administration of GM (400 mg kg-1) on four consecutive days increased pancreatic wet weight, protein and enzyme content of the gland. A preferential increase of proteinases above glucosidases was observed. Pancreatic lobules from inhibitor-treated rats released 30% less amylase in response to cerulein or carbachol when the rate of discharge was expressed in percent of initial content. Expressed in ku amylase/microgram DNA secretion rate was two-fold higher than in controls. In pancreatic duct cannulated rats GM (400 mg kg-1 h-1), introduced intragastrically on five consecutive days, stimulated volume-bicarbonate and protein secretion rate, the secretory response on the fifth day being significantly higher than on the first day. Enzyme pattern in pancreatic juice changed characteristically: mainly the amount of acidic proteinases increased, whereas the amount of the basic isoforms was altered only slightly. PMID- 3104053 TI - Maximal oxygen consumption and pulmonary circulation in patients with chronic bronchitis. AB - In order to study the relations between maximal oxygen consumption during exercise (VO2max) and the pulmonary circulation when pulmonary artery pressure (PPA) and pulmonary vascular resistance (PVR) are normal or close to normal, we evaluated twenty-three patients with chronic bronchitis, in stable clinical condition. All these patients performed a progressive exercise test on a bicycle ergometer until exhaustion (VO2max); they were also subjected to right heart catheterization at rest and during light exercise at constant load. In these patients with moderate functional impairment, we observed on average a significant, although weak, correlation (r = -0.52, P less than 0.01) between pulmonary vascular resistance at rest and VO2max. When VO2max exceeded 2 1 min-1, PVR was below 210 dyn s cm-5. From the heart rate during maximal exercise we computed the oxygen pulse (O2Pmax). In eight patients O2Pmax was reduced (less than or equal to 11 ml) with maximal heart rate close to its predicted value; in seven of these subjects PVR was abnormal and Ppa at rest was at least 20 mmHg. Thus it seems that in chronic obstructive bronchitis mild disturbances in pulmonary circulation may be a contributory factor in the limitation of exercise performance, and a maximal exercise test may help to detect pulmonary hypertension in these patients. PMID- 3104054 TI - Biliary cholesterol saturation in non-obese women and non-obese men before and after puberty. AB - The lipid composition of gallbladder bile was determined in forty-seven normal, non-obese subjects (twenty females and twenty-seven males) without gallstones ranging in age from seven months to twenty-nine years. Before puberty, bile was undersaturated with cholesterol in both sexes to the same extent. After puberty a marked increase in cholesterol saturation was observed in females but not in males (138% vs 88%; P less than 0.01). A significant correlation between age and cholesterol saturation could be observed in females (r = 0.546; P less than 0.05) but not in males. In addition a significant correlation between absolute weight and cholesterol saturation in all females (r = 0.827; P less than 0.001) and those after puberty (r = 0.659; P less than 0.05) could be demonstrated. In neither sex was saturation related to body mass index or ideal body weight. These findings suggest that saturation of bile raises in women during puberty but not in men, and this sex-related difference in cholesterol saturation probably contributes to the more common occurrence of gallstones in women than in men. PMID- 3104055 TI - Heparin half-life and sensitivity in normal subjects and in patients affected by deep vein thrombosis. AB - In some patients affected with deep vein thrombosis (DVT) it is necessary to administer large doses of heparin to achieve proper anticoagulation. To investigate the clinical relevance of this phenomenon, we studied the heparin half-life and the heparin sensitivity after a bolus IV injection of 60 i.u. kg-1 in seven healthy volunteers and eight DVT patients investigated on day 1 or 2 and again between day 10 and 20 of the heparin therapy. The heparin half-life, the in vitro and ex vivo heparin sensitivity, were comparable in the healthy volunteers and in the patients at both times of investigation. However, there were large interindividual variations in the controls and in the patients, not correlated to the levels of any coagulation factors. Thus, the heparin hyperconsumption phenomenon occasionally observed in a given patient reflected individual characteristics and was no value in the diagnosis of DVT. PMID- 3104056 TI - Antagonist capacities of nifedipine, captopril, phenoxybenzamine, prostacyclin and indomethacin on cyclosporin A induced impairment of rat renal function. AB - Experimental evidence indicates that cyclosporin A (CyA) nephrotoxicity is due to renal arteriolar constriction, reducing renal blood flow, glomerular filtration rate (GFR), and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle. The proximal tubular fractional reabsorption (PFR) is increased. Therefore, the impact on renal function of vasodilating agents was studied in rats given CyA. Conscious catheterized rats and clearance techniques were used. In acute experiments a preexisting CyA-nephrotoxicity was resistant to infusion of phenoxybenzamine, prostacyclin, captopril, nifedipine and indomethacin. Concomitant treatment with captopril and CyA did not improve renal function, while concomitant treatment with CyA and nifedipine improved GFR to 1.13 +/- 0.34 ml min-1 g-1 kidney weight (gKW) (n = 19, P less than 0.05), as compared to CyA and placebo treated controls (n = 12, 0.83 +/- 0.32 ml min-1 g-1 KW). Nifedipine also reduced FPR (88.6 +/- 5.1% vs. 83.2 +/- 5.6%. P less than 0.01), and increased lithium clearance from 99 +/- 54 to 184 +/- 64 microliters min-1 g-1 KW (P less than 0.001). The results are further evidence that CyA nephrotoxicity includes renal vasoconstriction, and indicates that calcium entry blockade is nephroprotective in the case of CyA toxicity. PMID- 3104057 TI - One year study of effects of an oestrogen-dominant oral contraceptive on serum high-density lipoprotein cholesterol, apolipoproteins A-I and A-II and hepatic microsomal function. AB - The effects over 1 year of an oestrogen-dominant oral contraceptive containing ethinylestradiol and levonorgestrel on serum high-density lipoprotein cholesterol, apolipoproteins A-I and A-II and liver microsomal enzyme activity assessed by antipyrine kinetics, were investigated in 21 healthy, young women. HDL cholesterol and apolipoprotein concentrations rose and hepatic microsomal enzyme activity fell during the first month of the treatment, and remained affected throughout the year. After discontinuation of treatment, the lipid and apolipoprotein concentrations and the microsomal enzyme activity returned to their pretreatment levels within 1 month. The drug, by reducing hepatic enzyme activity, may have influenced both the antipyrine elimination rate and the high density lipoprotein concentration. PMID- 3104058 TI - Treatment of persistent fetal circulation syndrome of the newborn. Comparison of different doses of tolazoline. AB - The effects of two doses of tolazoline have been compared in 2 groups of newborns suffering from the persistent fetal circulation syndrome. The effects on PaO2 and AaDO2 were similar in the 2 groups who received either a bolus of 1 or 0.5 mg X kg-1 tolazoline, followed by a continuous infusion of 1 or 0.5 mg X kg-1 X h-1. The observed changes did not differ significantly from those previously observed in babies treated with 2 mg X kg-1. A rise in PaO2 and a reduction in AaDO2 were usually observed shortly after the bolus injection and at plasma levels between 1.5 and 4 micrograms X ml X -1. A progressive rise in plasma level over time occurred after 1 mg X kg-1 (and in the previous study of 2 mg) but not with 0.5 g/kg tolazoline. The elimination half-life of tolazoline in 6 patients was 5 to 13 h. The data suggest that continuous infusion of tolazoline is not necessarily required and that the dose of 0.5 mg/kg is more appropriate and safer than the higher doses usually proposed. PMID- 3104059 TI - Pharmacokinetics of flecainide in patients with mild and moderate renal failure compared with patients with normal renal function. AB - We have studied the pharmacokinetics of flecainide after the oral administration of 100 mg to 8 patients without renal impairment and 8 patients with mild to moderate renal failure. Both groups gave comparable results with respect to the peak plasma concentrations and the time to peak. There was a significant correlation between renal flecainide clearance and endogenous creatinine clearance. The elimination half-time in the patients with impaired renal function was significantly longer (19.9, SD 9.9 h) than that in the patients with normal renal function (11.5, SD 4.2 h), but the variability in the elimination half-time in renal failure could not be explained on the basis of the available results. PMID- 3104060 TI - Involvement of the CD4 molecule in a post-activation event on T cell proliferation. AB - A monoclonal antibody (mAb) directed to a human leukocyte 55-kDa cell surface molecule with identical cellular distribution and biochemical properties to the CD4 was able to inhibit T cell proliferation induced either in a mixed lymphocyte culture or by activation with mAb anti-CD3, anti-CD2 or phytohemagglutinin. The inhibitory effect of anti-CD4 was observed in the absence of monocytes and was directly exerted on T4+ cells. This effect on cellular proliferation appears to be due to an inhibition of a postactivation event since the rise of cytoplasmic Ca2+ after activation with anti-CD3 mAb is not affected by the presence of anti CD4 and the proliferation that occurs after an activation pulse of 3 h with ionophore and phorbol myristate acetate can be inhibited when the anti-CD4 is added after the pulse period. Kinetic studies demonstrated that the inhibition of cellular proliferation by anti-CD4 mAb was observed even if the antibody was added as late as 18-24 h after the initiation of the culture. The effect of this blocking anti-CD4 mAb on the interleukin (IL) 2/IL 2 receptor signalling pathways was also examined. The presence of anti-CD4 slightly affected the production of IL2. In fact, addition of exogenous recombinant IL2 at the initiation of the cultures did not restore the proliferative response. However, anti-CD4 had a strong inhibitory effect on the expression of IL2 receptors as analyzed by direct immunofluorescence cytometry. Taken together, these results indicate that the binding of the anti-CD4 mAb to T cells interferes with a late metabolic step being capable of abolishing the proliferative activity of fully activated cells. PMID- 3104061 TI - Functional and biochemical characteristics of a murine interleukin 2 receptor inducing factor. AB - High density (resting) murine Lyt-2+ T cells exposed in vitro to the ligand concanavalin A (Con A) remain interleukin 2 (IL 2) unresponsive, i.e. do not express functional IL 2 receptors, unless reconstituted with accessory cells. This finding provides a bio-assay to define functional and biochemical characteristics of an IL 2 receptor-inducing factor (RIF). RIF bioactivity as secreted from the macrophage cell line P388-D1 is associated with a trypsin sensitive protein of 44 kDa which does not need to be glycosylated and which binds to and can be eluted from hydroxylapatite and phenyl-Sepharose. While both RIF and IL 1 are produced by accessory cells the lymphokines separate from each other according to functional and biochemical criteria. Either accessory cells, RIF or the protein kinase C activator phorbol myristate acetate can substitute for each other and are equally active for the induction of IL 2 responsiveness in high-density Lyt-2+ T cells exposed to Con A. To explain these results we conclude that in the mitogen system used, induction of IL 2 responsiveness (activation) represents a two-step event in which first cross-linking of cell surface structures by the ligand Con A excites the responder T cells, which subsequently respond to the accessory cell product RIF. PMID- 3104062 TI - Induction of interferon-gamma production and Ia expression by interleukin 1 in bone marrow culture cells. AB - Colony-stimulating factor-induced bone marrow (BM) cultures are a good source of antigen-presenting macrophages. However, they failed to present antigen to T cell clones when antigen was introduced as a short pulse only. Adding interleukin 1 (IL1) to BM culture cells before antigen pulse restored their antigen-presenting activity concomitant to a 2-10-fold increase in Ia antigenicity. We performed a series of experiments to test the mechanism of this IL1-induced activation. Our findings suggest that IL1 influences Ia expression and antigen-specific T cell proliferation by inducing interferon-gamma (IFN-gamma) production. IFN-gamma is produced in this system probably by residual Thy-1-positive cells in the BM cell culture. PMID- 3104063 TI - Specific lysis of Listeria monocytogenes-infected macrophages by class II restricted L3T4+ T cells. AB - Mice were infected with the intracellular bacterium, Listeria monocytogenes, and T cell clones from spleens, lymph nodes and peritoneal exudates were established. The capacity of L3T4+, Lyt2- T-cell clones to specifically lyse L. monocytogenes infected macrophages was analyzed. As a source of target cells, bone marrow macrophages (BMM phi) after 9 days of culture in hydrophobic teflon bags were used. These BMM phi were totally Ia-; however, significant Ia-expression could be induced by interferon-gamma (IFN-gamma). IFN-gamma-stimulated BMM phi, after priming with live or killed L. monocytogenes organisms were effectively lysed by the vast majority of L3T4+ T cell clones. In the absence of either IFN-gamma stimulation or antigen priming, no lysis occurred. Cytolysis was demonstrable in a conventional 4-h 51Cr-release assay and in an 18-h neutral red uptake assay and was antigen specific and class II restricted. Native T cells from L. monocytogenes-infected mice failed to lyse stimulated, L. monocytogenes-primed BMM phi and gained their cytolytic activity after antigenic restimulation in vitro. These data demonstrate that L. monocytogenes-specific L3T4+ T cells could lyse M phi presenting listerial antigens provided that Ia antigen expression had been induced. L3T4+ T cell clones produced IFN-phi after restimulation with antigen plus accessory cells in vitro and IFN-gamma secretion could be increased by costimulation with recombinant IL 2. These T cell clones conferred significant protection upon recipient mice which was more pronounced in the liver. The possible relevance of lysis by L3T4+ T cells of infected M phi to protection against and pathogenesis of intracellular bacterial infections is discussed. PMID- 3104064 TI - Simultaneous determination of the rates of synthesis and metabolism of dopamine in various areas of the rat brain: application to the effects of (+)-amphetamine. AB - A method is described in which two different dopamine turnover estimations are combined. The method is based on coadministration of a DOPA-decarboxylase inhibitor and a monoamine-oxidase inhibitor. This approach allows the simultaneous calculation of the biosynthesis rate of dopamine, as well as the formation rate of its main metabolite 3,4-dihydroxyphenylacetic acid. No mutual interference of the two turnover methods was observed. The method was applied in a dose-effect study of the influence of (+)-amphetamine on the synthesis and metabolism of dopamine. PMID- 3104065 TI - Antiarrhythmic effects of the thromboxane antagonist BM 13.177. AB - The effects of the thromboxane antagonist BM 13.177 (5 mg kg-1 + 0.15 mg kg-1 min 1) was investigated on the ventricular arrhythmias that result from coronary artery occlusion and reperfusion in anaesthetised open-chest greyhounds. BM 13.177 markedly reduced the severity and incidence of arrhythmias resulting from ischaemia; the number of ventricular ectopic beats was reduced from 1,084 +/- 159 (in controls) to 544 +/- 179 (in dogs given BM 13.177) and the incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF) were reduced from 86 to 22% and from 30 to 10% respectively. Following reperfusion the incidence of VF was 86% in controls and 44% in dogs given BM 13.177. Thus the total incidence of VF during the combined ischaemia-reperfusion insult was significantly reduced by treatment with BM 13.177 from 90% (in control dogs) to 50%. These results lend further support to the hypothesis that thromboxane is involved in the genesis of arrhythmias and that blockade of thromboxane receptors may be a suitable approach to antiarrhythmic therapy under conditions of ischaemia and reperfusion. PMID- 3104066 TI - CGS 15435A, a thromboxane synthetase inhibitor with an extended duration of action: a comparison with dazoxiben. AB - CGS 15435A, a novel thromboxane (Tx) synthetase inhibitor (5-chloro-1-methyl-2-(3 pyridyl)-3-indolhexanoic acid HCl), had a selectivity for Tx synthetase 100,000 fold greater than that for cyclooxygenase, PGI2 synthetase and lipoxygenase enzymes. In conscious beagles, 1 h following a single 3 mg/kg p.o. dose, serum TxB2 was inhibited 95% by CGS 15435 and 82% by dazoxiben (DAZ). Unlike the short acting Tx synthetase inhibitor DAZ, CGS 15435A significantly inhibited TxB2 formation 4, 6, 12 and 24 h after dosing. Serum levels of 6-keto PGF1 alpha and PGE2 were significantly increased following the administration of either drug. CGS 15435A and DAZ were further examined in a model with known Tx involvement. Thrombotic sudden death, produced in anesthetized rabbits by injection of 0.75 mg/kg arachidonic acid (AA) i.v. resulted in a 45% fall in the platelet count and 0% survival. Pretreatment with DAZ (8.6 mumol/kg i.v.) at 0.25 or 2 h pre-AA resulted in 3 and 42% thrombocytopenia and 100 and 0% survival respectively. CGS 15435A (8.6 mumol/kg i.v.) prevented the increases in plasma TxB2 levels, thrombocytopenia and sudden death with pretreatment at 0.25 h (0% thrombocytopenia and 100% survival) or 24 h (11% thrombocytopenia and 83% survival) before AA. These data indicate that CGS 15435A is a potent and selective Tx synthetase inhibitor with a long duration of action, and suggest that the compound could be useful in chronic, non-symptomatic indications of Tx involvement. PMID- 3104067 TI - Vasoconstrictor expression of human platelet-vessel wall interactions: inhibition by the Ca2+ entry blocker flunarizine. AB - Human blood platelets, stimulated with thrombin, induced contractions of isolated basilar artery segments of the dog. These platelet-mediated vascular contractions were inhibited in a concentration-dependent way by flunarizine, a Ca2+ entry blocker, selective for vascular tissues (IC50: 5.5 X 10(-7) M). This inhibition increased gradually as a function of the time contact with flunarizine, to reach its maximum after 60-90 min. Biochemical and pharmacological analyses using the S2-serotonin receptor antagonist ritanserin, the thromboxane A2/prostaglandin endoperoxide antagonist BM 13.177 and the fatty acid cyclo-oxygenase inhibitor suprofen showed that 5-hydroxytryptamine and prostanoids (thromboxane A2, prostaglandin endoperoxides) were the main mediators involved. The results further suggested amplification between the vascular effects of 5 hydroxytryptamine and prostanoids. Flunarizine did not affect the release of 5 hydroxytryptamine from platelets and did not interfere with their biosynthesis of thromboxane A2. PMID- 3104068 TI - Different mechanisms of the rabbit pulmonary arterial contraction caused by 5- or 6-hydroxydopamine. AB - The contractile responses of rabbit arterial strips to 5-hydroxydopamine (5-OHDA) or 6-hydroxydopamine (6-OHDA) were assessed in vitro. The 3H efflux from the pulmonary artery after preloading with [3H]noradrenaline was markedly enhanced by 100 microM 5-OHDA or 6-OHDA. In non-superfused strips, 6-OHDA produced a biphasic contraction, an initial small transient and a subsequent large sustained contraction, whereas 5-OHDA elicited a large monophasic contraction. The 6-OHDA evoked second large contraction was followed by a marked tachyphylaxis after repeated application of the drug. This contraction was greatly diminished by prazosin or cocaine and by pretreatment with reserpine, indicating an indirect action via noradrenaline release. In contrast, the initial contraction caused by 6-OHDA as well as the contraction caused by 5-OHDA was not inhibited by these agents, except prazosin, implying a direct action at the postsynaptic alpha 1 adrenoceptors. In addition, the concentration-response curve for noradrenaline was significantly shifted to the right by pre-addition of 5-OHDA whereas the curve for 5-HT was virtually unaffected. The results thus suggest that 5-OHDA acts as a postsynaptic alpha 1-adrenoceptor agonist. PMID- 3104069 TI - Comparison of the serum hormone levels and histological findings in pituitary adenomas. AB - Thirty patients with pituitary adenomas were investigated: 20 with growth hormone producing acromegaly, 7 with prolactinoma and 3 with hormonal inactive adenoma. The correlation between the serum PRL, GH, TSH, levels, their response to 200 micrograms i.v. TRH, measured before the transsphenoidal adenomectomy and the size, the light microscopic (H.E. and Mallory staining), immunocytochemical and ultrastructural (performed in 17 cases) picture of the adenomas were evaluated. CONCLUSIONS: (a) there is no close correlation between the hormone granules detected in the pituitary adenoma cells - by light microscopic, immunocytochemical and electron microscopic methods - and the serum hormone levels, their response to TRH; (b) in hormonally active adenomas the immunocytochemical as well as the ultrastructural findings could be negative; (c) in one disease more hormones could give an immunopositive reaction; (d) in any types of investigated adenomas the TSH immunopositivity was always accompanied by PRL immunopositivity (6 cases); (e) the size and the clinical (serum) or cytological hormone activity of the adenomas were independent of one another; (f) the basal serum hormone level shows the hormonal activity of the pituitary adenoma best of all. PMID- 3104070 TI - Inherited thyroxine-binding globulin excess. Study in a kindred. AB - A three-generation family with hereditary high thyroxine-binding globulin (TBG) serum levels has been studied. All patients were clinically euthyroid and did not have a goiter. Four females of the eleven members of the kindred had elevated TBG (range: 34-56 micrograms/ml), total thyroxine (T4) and total triiodothyronine (T3) levels, but normal free T4 (fT4) and normal response of thyroid stimulating hormone (TSH) to intravenous application of thyrotropin-releasing hormone (TRH). Microheterogeneity of TBG studied by isoelectric focusing showed a normal pattern. No variations of the four main bands as seen in other causes of TBG excess like liver diseases, estrogen therapy or pregnancy could be measured. The changes in TBG concentration seem to be due to an abnormal gene expression controlling synthesis of TBG. PMID- 3104071 TI - Hypothalamic GnRH and pituitary gonadotroph relationships during rat fetal life. AB - The ontogeny of hypothalamic GnRH, of pituitary and gonadal receptors and of pituitary LH and FSH was studied in the fetal and neonatal rat. Hypothalamic, hypophyseal and gonadal primordia were dissected from animals ranging in age from postconceptual day 12 to birth. Immunoreactive GnRH was detectable in the hypothalamus from fetal day 12 onwards at a low level until day 17, whereafter hypothalamic GnRH content and concentration increased until birth. GnRH receptors were reliably detectable in the pituitary anlage from fetal day 16 onwards and increased progressively with advancing age whether expressed as content or concentration. Signs of pituitary LH synthesis were evident as early as fetal day 12 but intrapituitary LH levels remained low until fetal day 17 when levels increased progressively until the end of gestation. Pituitary FSH was undetectable until fetal day 19, thereafter rising dramatically until the end of gestation. GnRH binding to testicular and ovarian tissues was undetectable throughout the period of fetal development. The possible relations among the developmental changes in hypothalamic GnRH, pituitary GnRH receptors and gonadotrophins are discussed. PMID- 3104072 TI - Cooperativity of ganglioside-dependent with protein-dependent substratum adhesion and neurite extension of human neuroblastoma cells. AB - The potential involvement of gangliosides in the adherence and neurite extension of human neuroblastoma cells (Platt and La-N1) was investigated on tissue culture substrata coated with the ganglioside GM1-binding protein, cholera toxin B (CTB) subunit, for comparison with similar processes on plasma fibronectin (pFN)-coated substrata. Cells attached with reduced efficiency on CTB substrata as compared with pFN substrata and required a much longer time to form neurite processes for a small percentage of cells on CTB. The specificity of these processes for GM1 binding was tested in a variety of ways. Supplementation of the cells with exogenous GM1, but not GD1a, identified a larger population of cells adherent on CTB (comparable to pFN-adherent cells) and dramatically increased the proportion of cells capable of forming neurites without reducing the time requirement. In ultrastructural studies using the scanning electron microscope (SEM) and immunofluorescence (IF) analyses to discriminate microtubule distributions, neurites of GM1-supplemented cells on CTB were virtually identical with pFN adherent neurites, whereas unsupplemented cells on CTB generated processes with fine-structural differences. Treatment of cells during the GM1 supplementation period with cycloheximide completely abolished the ability of cells to generate neurites on CTB and decreased the adhesive capacity of cells as well; a similar treatment of cells had no adverse effect on adherence or neurite extension on pFN. The importance of one or more proteins in GM1-dependent processes was further confirmed by demonstrating the trypsin sensitivity of a cell surface component(s) required to achieve maximal attachment on CTB; in contrast, adherence and neurite extension on pFN were much more resistant to this treatment process. Therefore, these experiments demonstrate that certain cell surface gangliosides are capable of mediating adherence and neurite outgrowth of human neuroblastoma cells on a suitable ganglioside-binding substratum; this ganglioside dependence is cooperative with one or more cell surface proteins which can now be analysed. These results are discussed in light of the identification in ref. [16] (Exp cell res 169 (1987) 311) of a second 'cell binding' domain on the pFN molecule competent for adherence and neurite extension of these neuroblastoma cells, as well as the potential role of pFN binding to a complex ganglioside on the surface of these neural tumor cells in these processes. PMID- 3104073 TI - Glycosaminoglycan synthesis and secretion by bovine retinal capillary pericytes in culture. AB - The synthesis and secretion of glycosaminoglycans (GAGs) was characterized in subcultures of bovine retinal capillary pericytes. The GAGs were metabolically labeled with [3H]glucosamine and 35SO4 for 3 days, and then precipitated from the cell layer or media by cetylpyridinium chloride and ethanol, separated by cellulose acetate electrophoresis and further identified by their susceptibility to degradative procedures. The predominant radioactively labeled GAG associated with the pericyte-cell layer was heparan sulfate (HS). Radioactively labeled chondroitin sulfate (CS) and hyaluronic acid (HA) were also present in the pericyte-cell layer. No radioactively labeled dermatan sulfate (DS) was detected. The profile of radioactively labeled GAGs secreted by pericytes into the media differed considerably from that associated with the cell layer. Equal amounts of radioactivity were incorporated into HS and CS. Small quantities of radioactively labeled HA were also present in the media. Although no radioactively labeled DS was detected in the pericyte-cell layer, it was present in the media. The total pericyte-cell layer GAG profile was determined by scanning densitometry of the three bands resolved after cellulose acetate electrophoresis and Alcian Blue staining. The slowest band was identified as HS, and accounted for 17% of the total GAGs. The middle band was identified as DS, and accounted for 34% of the total GAGs. The fastest band was tentatively identified as either DS or chondroitinase AC-resistant CS, and constituted 49% of the total GAGs. The GAGs associated with the fibroblast-cell layer and secreted into the media by fibroblasts also were characterized and compared with those produced by pericytes. The major differences were in the secretion of large amounts of HA into the media by fibroblasts, and the presence of radioactively labeled DS in the cell layer of fibroblasts. PMID- 3104074 TI - Synergistic activation of retinal capillary pericyte proliferation in culture by inositol triphosphate and diacylglycerol. AB - Inositol triphosphate (IP3) and diacylglycerol (DG) are second messengers which control ionic events implicated in cell proliferation in a variety of tissues. In order to determine if these two second messengers control the proliferation of bovine retinal capillary pericytes (BRCP) or feline retinal pigment epithelial cells (FRPE) in culture, both intact BRCP or FRPE or BRCP or FRPE made permeable by saponin were used to study the effects of IP3 and DG on [3H]thymidine incorporation into DNA. [3H]Thymidine incorporation by BRCP made permeable to saponin showed specific IP3 dose-dependence; the apparent Km was 0.3 microM of IP3. Similar effects of A23187, a Ca2+ ionophore, or synthetic DG (1-oleoyl-2 acetyl-glycerol) were also observed. The combination of synthetic DG (0-,2-,4-, 8 micrograms ml-1) and 1 microM A23187 produced greater stimulation of [3H]thymidine incorporation by intact BRCP than was seen with DG or A23187 alone. In contrast to BRCP. [3H]thymidine incorporation by FRPE was not stimulated by IP3, A23187 or synthetic DG. The synergistic activation of IP3 and DG provided direct evidence to support the view that BRCP proliferation in vitro were regulated by the levels of the two second messengers. PMID- 3104075 TI - Tissue plasminogen activator in avascular tissues of the eye: a quantitative study of its activity in the cornea, lens, and aqueous and vitreous humors of dog, calf, and monkey. AB - We analysed the tissue plasminogen activator (TPA) content of the corneal epithelium, endothelium, and stroma and of the lens, as well as the aqueous and vitreous humors, in dog, calf, and monkey eyes. A quantitative estimation of the TPA activity in the corneal tissues by the [125I]fibrin-coated well assay showed similar levels of activity in the corneal epithelium, stroma, and endothelium. However, some differences were observed among the three mammalian species analysed. The values, expressed in urokinase (UK) units of activity per mg protein, ranged from 0.8 +/- 0.22 to 1.03 +/- 0.23 for the epithelium, 0.47 +/- 0.13 to 0.98 +/- 0.2 for the stroma, and 0.48 +/- 0.11 to 0.93 +/- 0.22 for the endothelium. The lens, the vitreous and the aqueous humor yielded low to negligible values. However, by using the enzyme-linked immunosorbent assay (ELISA) method, we detected an appreciable amount of TPA in the lens (9.49 +/- 1.5 ng TPA per ml lens), corneal epithelium (1.43 +/- 0.29 ng TPA per mg protein) and vitreous humor of the dog (5.71 +/- 0.61 ng TPA per ml vitreous humor) and of the calf (5.7 +/- 0.44 ng TPA per ml vitreous humor). Such discrepancies may reflect species-specific variation in the TPA content of the tissues and possibly the limitations of the techniques utilized, because of the problem related to cross-reactivity between the TPA of a given species and the antibody used in the assays.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104076 TI - Is a fat metabolite the major diet dependent accelerator of aging? AB - Previous work with a high fat/low carbohydrate diet indicated that Drosophila melanogaster aged faster on that diet than on a high carbohydrate/low fat diet. This could be due to one of eight possibilities enumerated. Oxygen consumption of flies on the high fat/low carbohydrate diet is initially the same as that on the control diet. Subsequently the oxygen consumption falls to below control levels at older ages. No increased rate of living is indicated. A starvation resistant strain is described. The male eats less food, and yet maintains a body fat level indistinguishable from the parent strain. The lifespan and most physiological indices of aging used indicate that the process of aging is unchanged. Nutrient dilution produces a nearly compensatory increase in food intake with a reduced body fat and body energy reserves. The indices of aging used indicate that the rate of aging is reduced under these circumstances. These results are consistent with the possibility that fat or a fat metabolite alters the rate of aging. It is argued from previous data that body fat itself is not likely to be the important factor, rather a metabolite is probably involved. PMID- 3104077 TI - Spontaneous spike and wave discharges in thalamus and cortex in a rat model of genetic petit mal-like seizures. AB - In an inbred strain of Wistar rats, spontaneous spike and wave discharges (8 to 10 c/s) appeared regularly on the EEG during quiet wakefulness and were accompanied by an arrest of behavioral activity associated with vibrissal and facial myoclonia. These seizures were recorded over the entire neocortex, but predominantly in the frontoparietal cortex. Subcortical bipolar recordings in chronic preparations showed that the lateral thalamic nuclei were greatly involved in these discharges: high-voltage spike and waves always appeared either simultaneously with, or slightly before the cortical discharges. In some cases, thalamic discharges were not accompanied by cortical discharges. No discharges were recorded in medial thalamic nuclei, in the cingulate cortex, or in the hippocampus. These results confirm the thalamocortical prevalence in the development of these rats' petit mal-like seizures, with a possible driving from thalamic nuclei. PMID- 3104078 TI - Ascorbic acid content of neotropical plant parts available to wild monkeys and bats. AB - The ascorbic acid content of foliage available to wild primates and bats in Panama (in transition between wet and dry seasons) was lower than that of temperate zone foliage but higher than that of most fruits and vegetables. Intakes of ascorbic acid (mg/kg b.wt/day) by wild primates and frugivorous bats in Panama are much greater than that of most human populations. PMID- 3104079 TI - [Crystalline structure of the molecular complex 1-3 aminophenazone-thiourea]. PMID- 3104080 TI - [Method of perfusing the lateral cerebral ventricles of unanesthetized rats]. AB - A new technique permitting perfusion of the cerebral lateral ventricle and EEG recording simultaneously in intact rats and rats with an epileptogenic focus in the hippocampus is proposed. PMID- 3104081 TI - [Effect of tranquilizers on lipid peroxidation of biological membranes]. AB - Thirty-seven patients with unstable angina pectoris were treated with prolonged action nitrates for 20 days; 8 of these received additionally meprobamate in a dose of 0.4 g per day and 11 patients received phenazepam in a dose of 0.002 g per day. The addition of tranquillizers to the complex of treatment led to a significant decrease of one of the final products of biological membrane lipid peroxidation--Schiff's bases in erythrocytic membranes. During treatment with phenazepam a similar decrease was more rapid (by the 5th day of treatment) and more pronounced. PMID- 3104082 TI - [2-component inhibition of prostaglandin H synthetase by nonsteroidal anti inflammatory preparations]. AB - A combined effect on the irreversible inhibitor aspirin and fast reversible inhibitors ibuprofen, naproxen and sodium salicylate on prostaglandin-H synthetase was studied on microsomal fractions from ram vesicular glands. The fast reversible inhibitors were shown to bind to prostaglandin-H-synthetase at the same site as aspirin and thereby to protect the enzyme against irreversible inactivation by aspirin. PMID- 3104083 TI - 7-Mercaptoheptanoylthreonine phosphate functions as component B in ATP independent methane formation from methyl-CoM with reduced cobalamin as electron donor. AB - Purified methyl-CoM reductase of Methanobacterium thermoautotrophicum (strain Marburg) catalyzed the reduction of methyl-CoM to methane with reduced cobalamin, when either synthetic 7-mercaptoheptanoylthreonine phosphate (HS-HTP) or naturally occurring component B was present. With both compounds the same maximal specific activity was obtained and ATP was neither required nor stimulatory. These findings indicate that HS-HTP functions as component B and do not support the idea that HS-HT is only active in an adenosine monophosphorylated form. PMID- 3104084 TI - Possible involvement of prostaglandins in vasoconstriction induced by zymosan and arachidonic acid in the perfused rat liver. AB - Exposure of perfused livers to zymosan, arachidonic acid or phenylephrine but not to latex particles, stimulates hepatic constriction. The effects of arachidonic acid are rapid, reach a maximum after 2-3 min and then decline. They are blocked by the cyclooxygenase inhibitor indomethacin but not by the lipoxygenase inhibitor nordihydroguaiaretic acid. This suggests a role for prostaglandins in this action. Zymosan progressively increases hepatic pressure after a lag time of about 1 min. Perfusion of bromophenacyl bromide, indomethacin and nordihydroguaiaretic acid only partially inhibits the zymosan-induced vasoconstriction. None of these inhibitors effect the phenylephrine-induced response. Repeated infusion of arachidonic acid leads to homologous desensitization of the response whereas the response of the liver to phenylephrine is unaffected. The present data indicate that prostaglandins, produced and released within the liver, affect vasoconstriction in this organ. PMID- 3104085 TI - GTP dependence of the transduction of mitogenic signals through the T3 complex in T lymphocytes indicates the involvement of a G-protein. AB - The T3 molecule on the surface membrane of T lymphocytes is involved in the transduction of the proliferation signal generated by an interaction between the antigen receptor and an antigen, to the interior of the T cell. Mitogenic monoclonal antibodies against the T3 molecule and mitogenic lectins induce a rapid (within 5 min) protein synthesis-independent activation of ornithine decarboxylase (ODC) in human T lymphocytes. When T cells are selectively depleted of guanine nucleotides by treatment with mycophenolic acid, the early mitogen induced activation of ODC is completely inhibited. The inhibition rapidly reverted on the addition of guanine a few minutes before the mitogenic stimulation, and even more rapidly by GTP directly introduced into the T cells by a transient membrane permeabilization. GTP can be substituted for by a non hydrolyzable GTP analogue, GTP-gamma-S, which also induces ODC activity by itself in human T cells. These results suggest that a G-protein(s) is involved in the transduction of the proliferation signal in human T cells. PMID- 3104086 TI - The protein receptor for cholerabacteriophage phi 149. AB - Choleraphage phi 149 receptor activity was found in the outer membrane (OM) protein of Vibrio cholerae 154. Receptor protein for phage phi 149 was separated from trypsin-treated OM on a Sephadex G-100 column. Of the three peaks obtained, phage receptor activity was noted only in peak II. SDS-PAGE showed that the Mr of the protein was 35,000. The protein was heat-labile and protease-sensitive. The specificity of this protein as choleraphage phi 149 receptor was investigated by carrying out a protection experiment by anti-protein (peak II) rabbit sera. PMID- 3104087 TI - Human immunoglobulin heavy-chain multigene deletions in healthy individuals. AB - Extensive multigene deletions have been described in the human immunoglobulin heavy-chain constant region genes, some of them encompassing perhaps more than 100 kilobases. These deletions have all been observed in healthy individuals although these individuals lacked several immunoglobulin class or subclasses, being either homozygous for one deletion or heterozygous for two different deletions. The high frequency of consanguinity in the Tunisian population accounts for the high frequency of individuals displaying one or the other of these deletions in a homozygous state. PMID- 3104088 TI - Expression of the cell-binding domain of human fibronectin in E. coli. Identification of sequences promoting full to minimal adhesive function. AB - Two cDNA subfragments containing the cell-attachment site of human fibronectin (FN) were expressed as beta-galactosidase fusion proteins in E. coli. The products were purified to homogeneity by monoclonal antibody affinity chromatography and assayed for activity in a standard cell-adhesion assay. A fusion protein containing an 80 kDa fragment of human FN appeared functionally equivalent to intact FN purified from human plasma, whereas a truncated fusion protein of 33 kDa still containing a previously postulated cell-attachment site was approx. 50-fold less active. Our study establishes a system for analyzing adhesive protein function by DNA manipulation, rules out any major role for eukaryotic post-translational modifications in FN adhesive function, and localizes additional functional activity to a 1.3 kb region. PMID- 3104089 TI - Two distinct DNA ligases from Drosophila melanogaster embryos. AB - Embryos of Drosophila melanogaster contain two distinct DNA ligases (DNA ligase I and II). DNA ligase I was eluted at 0.2 M KCl and DNA ligase II at 0.6 M KCl on phosphocellulose column chromatography. The former was rich in early developing embryos and its activity decreased during embryonic development. The latter was found constantly throughout the developing stages of embryos. DNA ligase I existed in a cytoplasmic fraction and DNA ligase II is concentrated in nuclei. Both enzymes ligate 5'-phosphoryl and 3'-hydroxyl groups in oligo(dT) in the presence of poly(dA). DNA ligase II is also able to join oligo(dT)(poly(rA). Both enzymes require ATP and Mg2+ for activity. The Km for ATP is 2.7 X 10(-6) M for DNA ligase I, and 3.0 X 10(-5) M for DNA ligase II. DNA ligase I requires dithiothreitol and polyvinyl alcohol, but DNA ligase II does not. Both enzymes are inhibited in the presence of N-ethylmaleimide. DNA ligase I is active at a low salt concentration (0-30 mM KCl), but DNA ligase II is active at high salt concentrations (50-100 mM). DNA ligase I is more labile than DNA ligase II. The molecular masses of DNA ligase-AMP adducts were determined as 86 and 75 kDa for DNA ligase I, and as 70 (major protein) and 90 kDa (minor protein) for DNA ligase II under denaturing conditions. A sedimentation coefficient of 4.2 S was observed for DNA ligase II. Consequently, Drosophila DNA ligase I and II are quite similar to mammalian DNA ligase I and II. Drosophila DNA ligase I and a DNA ligase by B.A. Rabin et al. [(1986) J. Biol. Chem. 261, 10637-10645] seem to be the same enzyme. PMID- 3104090 TI - A new GTP-binding protein in brain tissues serving as the specific substrate of islet-activating protein, pertussis toxin. AB - A new GTP-binding protein serving as the specific substrate of islet-activating protein (IAP), pertussis toxin, was purified from porcine brain membranes as an alpha beta gamma-heterotrimeric structure. The alpha-subunit of the purified protein (alpha 40 beta gamma) had a molecular mass of 40 kDa and differed from that of Gi (alpha 41 beta gamma) or Go (alpha 39 beta gamma) previously purified from brain tissues. The fragmentation patterns of limited tryptic digestion and immunological cross-reactivities among the three alpha were different from one another. However, the beta gamma-subunit resolved from the three IAP substrates similarly inhibited a membrane-bound adenylate cyclase and their beta-subunits were immunologically indistinguishable from one another. Thus, the alpha 40 beta gamma is a new IAP substrate protein different from Gi or Go, in the alpha subunit only. PMID- 3104091 TI - Processing of Bacillus subtilis succinate dehydrogenase and cytochrome b-558 polypeptides. Lack of covalently bound flavin in the Bacillus enzyme expressed in Escherichia coli. AB - The DNA sequence of the Bacillus subtilis sdh operon coding for the two succinate dehydrogenase subunits and cytochrome b-558 (the membrane anchor protein) has recently been established. We have now determined the extent of N-terminal processing of each polypeptide by radiosequence analysis. At the same time, direct evidence for the correctness of the predicted reading frames has been obtained. The cytochrome showed a ragged N-terminus, with forms lacking one residue, and is inserted across the membrane without an N-terminal leader peptide. Covalently bound flavin was not detectable in B. subtilis succinate dehydrogenase expressed in Escherichia coli despite normal N-terminal processing of the apoprotein. This provides an explanation to why the succinate dehydrogenase synthesized in E. coli is not functional and demonstrates that host specific factors regulate the coenzyme attachment. PMID- 3104092 TI - Reannealing of phalloidin-treated actin filaments during recovery after sonication and its inhibition by beta-actinin. AB - Phalloidin (2 mol per mol actin)-treated pyrenyl F-actin showed a critical concentration of 1.8 microM in the presence of 10 mM KCl, 0.2 mM ADP, and 5 mM Tris-HCl buffer, pH 8.0 at 25 degrees C. The filament weight concentration did not change at all during and after sonication, yet degrees of flow birefringence increased and the filament number concentration decreased after the termination of sonication. The latter changes were not affected by EDTA, but inhibited by beta-actinin. These observations suggest that reannealing of short pieces of phalloidin-treated actin filaments fragmented during sonication takes place during recovery after sonication. PMID- 3104093 TI - Competition between tetracycline and tRNA at both P and A sites of the ribosome of Escherichia coli. AB - Fluorescence anisotropy studies performed on 6-demethylchlortetracycline, binding to the ribosome of E. coli in competition with tRNA at the P site or at both P and A sites, have provided a quantitative assessment in situ of the interaction of this antibiotic with the A site and have demonstrated that there is also an interaction between tetracycline and the P site. PMID- 3104094 TI - In-situ breakage of an implantable venous access system. AB - A totally implantable system for venous access (Port-A-Cath, Pharmacia, Nu-tech) has now entered clinical use. This system consists of a silastic catheter secured to a stainless steel reservoir with a locking ring. The system has been shown to have several advantages when compared with earlier venous access systems. However, the advantages of total implantation have also disposed the system to new complications. Two cases are presented of patients who had this system placed and developed in-situ separation of the catheter from the reservoir. The catheter was removed surgically from the subcutaneous tissues in one patient and with a Dormain basket in the second because complete migration of the catheter into the central venous system had occurred. In neither patient could the precise cause for the separation be ascertained. However, it can be appreciated that if chemotherapeutic agents were infused in these patients the results would have been disastrous. It is recommended that if blood cannot be easily aspirated after gentle to and fro flushes with a 10 ml syringe, a chest radiograph be obtained prior to the infusion of any substance to check for continuity in the system. Any breaks in the system should be immediately repaired since migration of the catheter into the venous system can occur. PMID- 3104095 TI - Short-term pituitary desensitization to luteinizing hormone-releasing hormone (LH RH) after pulsatile LH-RH administration in women with amenorrhea of suprapituitary origin. AB - The existence of a short-term pituitary desensitization in luteinizing hormone (LH) release to single doses of luteinizing hormone-releasing hormone (LH-RH) in the ovariectomized rat was recently disclosed. The purpose of the present study was to investigate whether this refractoriness is also present in humans. Blood from six women with amenorrhea of suprapituitary origin was sampled every 10 minutes for 300 minutes for determination of LH and follicle-stimulating hormone (FSH). A pulse of 20 micrograms LH-RH was given intravenously 90 and 210 minutes after the first blood sample, and 2 micrograms LH-RH was given 30, 150, 240, and 270 minutes after t0. The mean maximal increments of LH and FSH were compared. The LH response to a 2-micrograms LH-RH bolus given 30 (t240) or 60 (t150) minutes after a 20-micrograms LH-RH pulse was significantly decreased, compared with the initial response to this dose at t30. For both LH and FSH, the response to 2 micrograms LH-RH given 30 minutes after the 20-micrograms pulse (t240) was almost absent, compared with 60 (t150) minutes after the 20-micrograms dose. We conclude that a short-term pituitary refractoriness to LH-RH is present after administration of single pulses of LH-RH in women with amenorrhea of suprapituitary origin and pulses of LH-RH in the physiologic range (2 micrograms) given to these women do not always generate LH and FSH increments that are identifiable as significant hormone pulses. PMID- 3104096 TI - Pharmacologic induction of multiple follicular development improves the success rate of artificial insemination with husband's semen in couples with male-related or unexplained infertility. AB - The use of artificial insemination with husband's semen (AIH) as treatment for couples with male-related or unexplained infertility is often disappointing. The aim of the present study was to evaluate whether the induction of multiple ovulation can increase the pregnancy rates in couples treated with AIH. Multiple follicular development was induced by means of clomiphene citrate (CC) plus purified follicle-stimulating hormone (FSH) in 17 couples undergoing AIH for male related or unexplained infertility. In spite of the long duration of infertility (greater than 6 years), 10 couples (58.8%) achieved pregnancy within 6 months of treatment. This figure was significantly higher than that obtained in 120 couples who underwent AIH either during spontaneous cycles or after induction of follicular development with CC alone. These results suggest that the availability of multiple mature oocytes increases the conception rate during each cycle, as reported for in vitro fertilization (IVF) programs. It is therefore suggested that a trial of induction of multiple follicular development be performed in couples with male-related or unexplained infertility before their inclusion in protocols for invasive procedures, such as IVF or gamete intrafallopian transfer. PMID- 3104097 TI - Anterior pituitary dysfunction during the luteal phase following ovarian hyperstimulation. AB - The capacity of the pituitary to secrete prolactin (PRL) and gonadotropins was investigated during the luteal phase of eight normally menstruating tubal infertility patients after ovarian stimulation with clomiphene citrate, human menopausal gonadotropin, and human chorionic gonadotropin. The baseline values of PRL were significantly higher (P less than 0.025), those of luteinizing hormone unchanged, and those of follicle-stimulating hormone lower (P less than 0.025) during the treatment than in the control cycles. The maximal response of PRL to the dopamine antagonist metoclopramide was increased (P less than 0.01), whereas the maximal responses of luteinizing hormone (P less than 0.025) and follicle stimulating hormone (P less than 0.001) to gonadotropin-releasing hormone were lowered in the treatment cycles. The current results indicate that ovarian hyperstimulation with clomiphene citrate/human menopausal gonadotropin/human chorionic gonadotropin may induce luteal phase pituitary dysfunction, which may affect the luteal phase functions of the corpus luteum. PMID- 3104099 TI - Decreased ovarian response to human menopausal gonadotropin caused by subcutaneously administered gonadotropin-releasing hormone agonist. PMID- 3104098 TI - Effects of soluble products of activated lymphocytes and macrophages (lymphokines and monokines) on human sperm motion parameters. AB - Experiments were conducted to evaluate the effects of supernatants from activated leukocyte cultures and purified lymphokine and monokine preparations on sperm motion. An automated semen analyzer was used to obtain accurate measurements of several parameters of sperm motion. Supernatants from activated peripheral blood leukocyte cultures significantly decreased sperm motility. In studies of effects of individual lymphokines and monokines, significant antimotility effects were observed when spermatozoa were incubated with the lymphokine gamma-interferon and the monokine tumor necrosis factor. Subnormal fertility may result from defective sperm function caused by lymphokines and monokines elaborated by activated lymphocytes and macrophages residing in the reproductive tracts of infertile men and women. PMID- 3104100 TI - [Electrical reaction of the cerebellar cortex to stimulation of the medial mammillary nucleus and dorsal hippocampus]. PMID- 3104101 TI - Intraocular argon laser photocoagulation. AB - Intraoperative photocoagulation using an endolaser delivery system is an important recent development in the field of vitreous microsurgery. Endolaser photocoagulation is indicated in a wide variety of vitreoretinal disorders and offers important advantages over previous techniques of endophotocoagulation using xenon energy. We review our experiences of argon laser endophotocoagulation to identify the role of this technique, the potential hazards and stringent precautions required for theatre personnel. PMID- 3104102 TI - [Studies on cytosol thyroid hormone binding proteins in the rat liver: Part II. Alterations of thyroid hormone binding proteins in various thyroid function states]. AB - Alterations of binding characteristics of cytosolic thyroid hormone binding proteins (CTHBPs) were examined in livers of rats with different thyroid function. Seven days after thyroidectomy, rats were divided into three groups. Group I received no treatment. Group II was treated with 230 ng triiodothyronine (T3)/100 g body weight per day for three days, and Group III with 40 micrograms T3/100 g body weight per day for three days. On the fourth day, each rat was given 0.7 microCi of 125I-T3/100 g body weight intraperitoneally and exsanguinated two hours later. During three days' treatment, body weight in Group II increased significantly compared with that in Group I (P less than 0.05), and body weight in Group III actually decreased. The ratio of liver weight to body weight in Group II was significantly higher than that in Group I or Group III (P less than 0.01). Percent distributions of 125I-T3 in cytosol fraction per liver or concentrations of cytosolic protein did not differ significantly among these three groups. Serum T3 concentrations (mean +/- SD ng/ml: Group I; not detectable, Group II; 0.50 +/- 0.27, Group III; 7.10 +/- 2.31), cytosolic T3 concentrations (mean +/- SD ng/ml: Group I; not detectable, Group II; 0.59 +/- 0.26, Group III; 10.38 +/- 3.08) and mitochondrial alpha-glycerophosphate dehydrogenase activities (mean +/- SD delta OD500 millimicrons/min/mg: Group I; 28.0 +/- 1.5, Group II; 46.7 +/- 7.3, Group III; 267.7 +/- 9.1) suggested that Group I was in hypothyroid state, Group II in euthyroid state and Group III in thyrotoxic state. Binding characteristics of cytosolic T3 binding protein (CT3BP) were different among the three groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3104103 TI - [Studies on cytosol thyroid hormone binding proteins in the rat liver: Part III. Partial purification and binding characteristics of thyroxine-binding protein in hypothyroid rat liver cytosol and serum]. AB - Cytosolic thyroxine-binding protein (CT4BP) was partially purified from rat liver cytosol obtained 10 days after thyroidectomy using Sephadex G-200 gel filtration, and its binding characteristics were analyzed in displacement experiments using a charcoal binding method to separate bound and free hormones. Serum T4-binding proteins were also partially purified, and their binding characteristics were similarly determined. Sephadex G-200 gel filtration of liver cytosol from thyroidectomized rats revealed that CT4BP had an apparent molecular weight of 100 X 10(3) daltons. CT4BP had a very high affinity constant (Ka) of 2.2 +/- 10(10) M 1 and a small maximum binding capacity (MBC) of 5.1 X 10(-9) g/mg. protein for T4. Relative affinities of T4 analogues for CT4BP (if the affinity of L-T4 was assigned a value of 100, then D-T4 would have a value of 25.3; L-T3, 16.6; D-T3, 2.3; reverse T3, 1.4 and both Tetrac and Triac less than 1) showed that CT4BP had a rigid specificity for alanine-side chain of T4-molecule. This CT4BP was not demonstrated when cytosol from normal rat liver was used. Sephadex G-200 gel filtration of rat serum obtained 10 days after thyroidectomy revealed two T4 binding proteins. The faster peak (Peak I; MW about 100 X 10(3) daltons) was eluted before the albumin peak, and the slower peak (Peak II; MW about 56 X 10(3) daltons) appeared after the albumin peak. Peak I was barely detectable when normal rat serum was used. Peak I had a higher Ka of 2.0 X 10(10) M-1 and a smaller MBC of 3.9 X 10(-9) g/mg. protein than Peak II (Ka; 8.9 X 10(8) M-1, MBC; 3.7 +/- 10(-7) g/mg. protein). Relative affinities of T4 analogues for Peak I (L T4 100, D-T4, 34.9, L-T3 11.1, D-T3 1.8, reverse T3 6.8, Tetrac 0.25 and Triac 0.1) showed that Peak I had a rigid specificity to alanine-side chain of T4 molecule, but Peak II had little specificity to this side chain (L-T4 100, D-T4 9.2, L-T3 2.1, D-T3 1.0, reverse T3 14.3, Tetrac 69 and Triac 26.3). Thus, Peak I had a similar binding characteristics to those of human thyroxine-binding globulin (TBG), and Peak II was comparable to human thyroxine-binding prealbumin (TBPA). The results that both molecular weight and binding characteristics were similar between CT4BP and Peak I suggest that both proteins are identical, being comparable to human TBG. This must be clarified in future. PMID- 3104104 TI - [Surgical treatment of angiokeratoma corporis circumscriptum naeviforme]. PMID- 3104105 TI - Behavior of cutaneous Langerhans' cells and skin reactivity after gold sodium thiomalate treatment of pemphigus vulgaris. AB - Skin biopsies from pemphigus vulgaris patients in the acute phase of disease and after successful GST therapy were studied in respect to their capacity to express OKT6, OKIa1 and HLA-DR antigens. In comparison to controls, the epidermis overlaying noninvolved skin contained significantly (p = 0.0001) fewer detectable Ia and T6 antigen-bearing Langerhans' cells. Lower epidermal Langerhans' cell density in comparison to controls was detected in both prednisolone-treated and untreated patients. A normalization of prior defective antigen expression was observed in patients in remittence after GST therapy. This correlated with a normal delayed type hypersensitivity reaction (Multitest Merieux). PMID- 3104106 TI - Remission of psoriasis with etidronate treatment of underlying Paget's disease of bone. AB - The case is reported of a 64-year-old man in whom psoriasis developed in relation to Paget's disease of the underlying bone. Treatment of Paget's disease was associated with remission of psoriasis. We suggest that local hyperaemia is the common link in this association and that this lends support to the theory that vascular factors are important in the pathogenesis of psoriasis. PMID- 3104107 TI - Acid-base evaluation of umbilical cord blood: relation to delivery mode and Apgar scores. AB - Acid-base status of umbilical artery and vein blood was measured immediately after delivery in 300 cases. A slight acidosis of mixed respiratory/metabolic type was found in newborns delivered following a second stage of 10-30 min duration. After a second stage of more than 30 min the metabolic contribution to the acidosis was predominating. With Apgar scores lower than 10 the pH was found to decrease and carbon dioxide tension to increase. Induction or augmentation of labor by oxytocin did not influence the acid-base status of umbilical cord blood. Delivery by vacuum extraction or low forceps resulted in lower pH and higher carbon dioxide tension in umbilical cord blood, but the changes were associated with the indication for instrumental delivery and not with mode of delivery. A large arterio-venous difference between the acid-base parameters was usually connected to vigorous newborns and a small difference to depressed infants. The carbon dioxide tension was usually increased in newborns with decreased pH, and a close correlation between these parameter was found. No case of acidosis (pH below 7.15) was found in this population at carbon dioxide tensions below 7.2 kPa; at higher Pco2 values only 25% of the newborns were acidotic. A Pco2 level of 7.7 kPa might be used at transcutaneous carbon dioxide monitoring during labor, although the sensitivity and specificity of this parameter will have to be decided in a prospective study. PMID- 3104108 TI - Obstetric factors associated with cord blood gas values at birth. AB - Values of pH, base deficit and Pco2 in 885 unselected samples of umbilical blood collected at birth were related to pregnancy and delivery details. An increase in acidosis in both umbilical vein and artery was associated with placental abruption, maternal pethidine, pre-eclampsia, primigravidity, vaginal operative delivery for fetal distress and a long second stage of labour. Increased acidosis in arterial, but not venous, blood occurred with cord entanglement, vaginal breech delivery, postmaturity, high birthweight and a long first stage of labour. The relationship between obstetric factors and the acid-base state of the neonate suggests a possible role for cord blood gas measurements in assessing the results of obstetric practice. PMID- 3104109 TI - The role of Gs in activation of adenylate cyclase. PMID- 3104110 TI - The interaction of lithium ions with inositol lipid signalling systems. PMID- 3104111 TI - Mammalian G proteins: structure and function. PMID- 3104112 TI - The use of specific antibodies to identify and quantify guanine nucleotide binding proteins. PMID- 3104113 TI - Activation of protein kinase C is coupled to prostaglandin F2 alpha synthesis in the ovary: studies in cultured swine granulosa cells. AB - We have investigated the role of phospholipid-sensitive calcium-dependent protein kinase (protein kinase C) in prostaglandin F2 alpha synthesis by monolayer cultures of swine granulosa cells. In this system, specific phorbol ester derivatives known to activate protein kinase C significantly augmented the production of prostaglandin F2 alpha. Phorbol ester in conjunction with the ionophore A23187 synergistically increased prostaglandin F2 alpha production. These stimulatory actions were dose- and time-dependent, and could be abolished by the cyclooxygenase inhibitor, indomethacin, or the protein synthesis inhibitor, cycloheximide. Moreover, the rank order of potency of phorbol esters in enhancing prostaglandin F2 alpha production was concordant with that demonstrated for activation of protein kinase C in the swine ovary. In addition, a nonphorbol stimulator of protein kinase C, 1-octanoyl-2-acetylglycerol, also significantly enhanced prostaglandin F2 alpha biosynthesis. The synthesis of immunoassayable prostaglandin F2 alpha was confirmed by high-pressure liquid chromatographic purification of this radiolabeled metabolite of [3H]arachidonic acid. Thus, the present studies indicate that the protein kinase C effector pathway in the swine granulosa cell is functionally coupled to prostaglandin F2 alpha production. PMID- 3104114 TI - Sulfated glycosaminoglycans (GAG) in the developing mouse brain. Quantitative aspects on the metabolism of total and individual sulfated GAG in vivo. AB - Sulfation and desulfation of total glycosaminoglycans (GAG) as well as of chondroitin sulfates (A + C), dermatan sulfate, and heparan sulfate were quantified in the developing cerebrum and cerebellum of mice by labeling with [35S]sulfate combined with chases started 24 hr after [35S]sulfate injection. In both the developing cerebrum and cerebellum, the rate of biosynthesis of total sulfated GAG was highest shortly after birth (2 days), decreased sharply thereafter, and reached a plateau after 14 days. The biosynthetic activities of chondroitin sulfates and heparan sulfate decreased sharply up to 14 days and retained constant levels afterward. By contrast, the rates of biosynthesis of dermatan sulfate increased up to 14 days. The biodegradation rates of total sulfated GAG as well as of chondroitin sulfates, heparan sulfate, and dermatan sulfate were strongly correlated with the corresponding rates of biosynthesis during the first 2 postnatal weeks. Total and individual sulfated GAG showed high degradation rates resulting in half-life times of a few hours up to 1 1/2 days. Thus sulfated GAG are synthesized in excess and the actual net content seems to be co-regulated to a high degree by lysosomal degradation. In both brain parts, a proportional increase of the sulfated GAG content vs the total GAG content from 40% at birth to 90% at 28 days was observed. Since during development heparan sulfate and dermatan sulfate manifested a relative increase in their daily net synthesis besides a decrease of chondroitin sulfates, a developmental increase of the sulfate groups linked to GAG is evidenced. This molecular differentiation resulting in microenvironmental changes may be of high functional significance. PMID- 3104115 TI - Characteristics of two types of meningococcal group C polysaccharide conjugates using tetanus toxoid as carrier protein. AB - Effective meningococcal vaccines have to induce protection against groups A, B, C, W-135 and Y meningocci. Polysaccharides are the most effective vaccine candidates against groups A, C, W-135 and Y meningococci. The vaccine potential of polysaccharides is enhanced by conjugating the polysaccharides to carrier proteins. This paper describes the preparation and immunological characterization of two types of group C polysaccharide - tetanus toxoid conjugate. Both types of conjugate were produced by different procedures. Procedure i. depends on cross linking of both components with N-ethyl-N'-(3-dimethylaminopropyl) carbodimide. Procedure ii. is a more monofunctional way of conjugating partially depolymerized polysaccharide with tetanus toxoid by reductive amination. The antigenic activity of the tetanus toxoid component of the conjugates containing this carrier protein was studied in ELISA and showed differences between the conjugate preparations. The immunogenic activity of all conjugate preparations was tested in mice. All conjugates produced IgG antibodies to the polysaccharide component, although the booster effects of procedure ii. conjugates were less pronounced than those of procedure i. conjugates. The immunogenic activity of the tetanus toxoid component of the various conjugate preparations correlated rather well with their antigenic activities as measured in ELISA. PMID- 3104116 TI - Pitfalls of single radial immunodiffusion techniques used for the quantification of influenza haemagglutinin. AB - In the case of Tween-ether split vaccines the quantification of haemagglutinin is not achievable by the single radial immunodiffusion test alone. Aggregate formation of solubilized haemagglutinin frequently occurs when the applied detergent is removed and, therefore, a physico-chemical method including an effective disaggregation procedure like SDS treatment in combination with PAGE is recommended. PMID- 3104117 TI - The virtual elimination of rubella and mumps from the United States and the use of combined measles, mumps and rubella vaccines (MMR) to eliminate measles. AB - The measles elimination effort, which began in 1978, has made dramatic contributions to the virtual elimination of rubella and congenital rubella syndrome (CRS) and the control of mumps in the USA. The use of combined MMR vaccine has resulted in immunization levels at school entry in excess of 95% against each of these diseases. As a result, record low levels of rubella, CRS, and mumps were reported in 1984. Continued use of MMR, along with improved surveillance and aggressive response to outbreaks, can be expected to eliminate rubella and mumps as well as measles. PMID- 3104118 TI - Comparative toxicology of tetrachlorobiphenyls in mink and rats. I. Changes in hepatic enzyme activity and smooth endoplasmic reticulum volume. AB - Mink have been shown previously to be extraordinarily sensitive to polychlorinated biphenyls (PCBs) and related classes of halogenated hydrocarbons. This study explored several aspects of the acute response of mink to two purified tetrachlorobiphenyl (TCB) congeners and compared their response with that of the rat, a less sensitive and more thoroughly studied species. Young female pastel mink and young female Sprague-Dawley rats received three daily intraperitoneal injections with equimolar doses of either 2,4,2',4'-TCB or 3,4,3',4'-TCB, and were sacrificed after 7 days. Two control groups were used for each species; one was allowed free access to food and the other was pair-fed to the 3,4,3',4'-TCB treatment group. Rats remained clinically normal, while mink treated with 3,4,3',4'-TCB developed severe anorexia, diarrhea, and melena. Both species had significant increases in hepatic cytochrome P-450 content and the characteristic shift in the spectral maxima from 450 to 448 nm in the 3,4,3',4'-TCB- but not in the 2,4,2',4'-TCB-treated animals. Rats but not mink had increased activities of several hepatic monooxygenases in response to both congeners while microsomal epoxide hydrolase was increased in rats after 2,4,2',4'-TCB and in mink after 3,4,3',4'-TCB. Significant increases in the relative volume of smooth endoplasmic reticulum within hepatocytes of 2,4,2',4'-TCB-treated rats but not mink were confirmed by ultrastructural morphometry. Accumulation of both congeners was greater in adipose tissue than in the liver of either species. In both species, concentrations in adipose tissue were much greater for 2,4,2',4'-TCB than for 3,4,3',4'-TCB. PCB toxicosis in mink, as in other species, appeared to be dependent on isomeric arrangement of chlorine substituents. However, unlike other species, the toxicosis was not associated with biochemical or morphological evidence of hepatic enzyme induction. Moreover, the target organ of 3,4,3',4'-TCB toxicosis in mink was the small intestinal mucosa. PMID- 3104119 TI - Nitrogen deficits in aroclor 1254-treated rats. AB - Nitrogen balance and the efficiency of retaining assimilated dietary nitrogen (biological value) were evaluated in Aroclor 1254-treated (ARO) rats and in vehicle-treated, pair-fed (PF) and ad libitum-fed (AF) rats (150-190 g). ARO treated rats (300 mg/kg/day, po on 4 consecutive days) lost weight and consumed less chow than the AF group while the weight of the PF rats was not different from those of either the ARO or AF groups. The nitrogen balance and the biological value for the ARO rats were also significantly less than those of the AF rats whereas the PF controls were not different. The ingested calories (expressed in kcal/(kg body wt)0.73) by the ARO and PF rats were equal, but were less than those of the AF group. The ARO and PF groups excreted the same amounts of fecal nitrogen which were less than the fecal nitrogen excretion by the AF rats. The absorbed fraction of the ingested nitrogen was the same among all groups, which indicated that the digestibility and absorption of the dietary nitrogen were not changed. By contrast, the ARO group excreted the same amount of urinary nitrogen and urea as AF rats while the PF group excreted significantly less urinary nitrogen than the latter controls. Thus, the loss of nitrogen by the ARO group was attributed to increased excretion of urinary nitrogen, most likely as urea, in relation to the nitrogen intake. The nitrogen retention and balance in rats with ARO exposure are similar to the response in rats fed a diet of low biological value except that the influence of ARO on nitrogen metabolism occurred during the postabsorption phase. PMID- 3104120 TI - Chloroform hepatotoxicity in the Mongolian gerbil. AB - CHCl3 hepatotoxicity was studied in the male Mongolian gerbil and compared to that in the male Sprague-Dawley strain rat. Based on elevations in serum transaminase activities in response to CHCl3 exposure, control gerbils were more sensitive to CHCl3 than were gerbils treated with phenobarbital, chlordecone, mirex, or 3-methylcholanthrene. The increased sensitivity of the control relative to the induced gerbil was consistent with earlier observations of CCl4 hepatotoxicity (Ebel, R. E., and McGrath, E. A., 1984, Toxicol, Lett., 22, 205 210). Microsomal enzyme concentrations or activities were not decreased in the control or induced gerbils in response to CHCl3 exposures of up to 200 microliter/kg. At a dose of 500 microliter/kg, cytochrome P-450 and its reductase were decreased by about 25% in the chlordecone-induced gerbil. In contrast, chlordecone- and phenobarbital-induced rats were sensitive to CHCl3 as evidenced by marked elevations in serum transaminase activities, decreases in microsomal enzyme concentrations or activities, and a transient decrease in hepatic nonprotein sulfhydryl groups. Control rats were insensitive to CHCl3. Histopathological changes in the livers of these animals were consistent with alterations in the biochemical parameters measured. The relationship between sensitivity to the hepatotoxic effects of CHCl3 and CCl4 was different for the gerbil and rat. PMID- 3104121 TI - The relationship between benzo(a)pyrene diol-epoxide-DNA adducts and mutagenicity in the CHO/HPGRT assay. AB - We have studied the relationship between DNA adducts in Chinese hamster ovary (CHO) cells and mutagenicity as determined in the CHO/hypoxanthine-guanine phosphoribosyltransferase assay. The cells were treated with benzo(a)pyrene 7,8 diol (BP-diol) in the presence of a bioactivation system, S9 mix. DNA binding by bioactivation of BP-diol with S9 mix occurred with both stereoisomers of benzo(a)pyrene diol-epoxide (BPDE) in approximately equal amounts. The number of BPDE-DNA adducts (21-260 adducts/10(6) nucleotide base pairs) increased with increasing treatment concentrations of BP-diol (1.4-7.0 microM). A linear relationship was observed between the number of BPDE-DNA adducts and mutagenicity (89-605 mutants/10(6) cloneable cells) over the concentration range of BP-diol assayed. PMID- 3104122 TI - The first year of an urban family practice. AB - The first year of an urban based family practice partnership, composed of one male and one female physician, was followed to determine disease diagnosis distribution and frequency, patient residence, and types and numbers of office procedures and laboratory tests. The diagnosis distribution and frequency were compared to studies conducted in other regions of the nation. Each partner's practice was analyzed separately to assess whether there were differences in their practices dependent on the sex of the provider. During the year, the physicians had 3,059 patient visits and recorded 4,711 problems. In all, 773 office procedures were performed; the most common were related to health maintenance. The 1,554 laboratory tests performed also showed a concentration for the purpose of health screening. This practice was less active in the areas of acute trauma and obstetrics than other reported studies. Few differences in the individual practices of the male and female physicians were noted. Categorizing the problems according to the revised diagnostic clusters demonstrates the usefulness of that system. In spite of the urban nature of the practice, a high percentage of patients using the family practice office lived in the surrounding neighborhood. PMID- 3104123 TI - [Hemodynamic and anti-angina effects of transdermal nitroglycerin after acute and chronic administration. Additive effect of sublingual isosorbide dinitrate]. AB - To evaluate the acute and chronic anti-anginal efficacy of a Transdermal Therapeutic System, releasing 10 mg of nitroglycerin over 24 hours (TTS 10), and possible additional effects of isosorbide dinitrate 5 mg (ISDN) sublingually (s.l.), ten patients with stable exercise-induced angina pectoris and pathological coronary angiography were studied. The protocol of the trial consisted of an initial acute study, carried out in double-blind conditions and following a cross-over design, to compare TTS 10 and placebo. Cycloergometric exercise tests were performed on the first and second day, 3 hours after dosing. After a 30 minute rest period, a sublingual 5 mg dose of ISDN was given and 15 minutes later a further exercise test was carried out. Subsequently, patients received TTS 10 in single-blind conditions for 16 days. On the 15th and 16th day, stress test was repeated, 3 hours after the application of active plasters and, 30 minutes later, a further exercise test was performed, 15 minutes after a sublingual dose of ISDN 5 mg or placebo, given in double-blind conditions and in randomized sequence. After acute and chronic administration, TTS 10 significantly improved exercise tolerance in comparison with placebo. During the first acute study, ISDN 5 mg s.l., led to a significant reduction in systolic BP, a reflex increase in heart rate and a further improvement in exercise tolerance, whether patients were on placebo or TTS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104124 TI - Effects of a transdermal patch system containing nitroglycerin on exercise tolerance in patients with angina pectoris. Double-blind, placebo controlled, comparison with slow-release nifedipine and verapamil. AB - The antianginal efficacy of nitroglycerin (NTG), given in a new transdermal therapeutic system (TTS), was compared with that of nifedipine and verapamil, both in slow-release (SR) formulation, in a randomized, double-blind, placebo controlled study, carried out in 8 patients with stable exercise-induced angina pectoris. TTS NTG 40 cm2 (releasing 20 mg of NTG over 24 hours), nifedipine 20 mg SR, verapamil 120 mg SR and placebo were given once on 4 consecutive days according to a 4 X 4 latin-square design, twice replicated. A cycloergometric symptom-limited exercise test was performed 4 and 8 hours after the administration of each drug. Four hours post-dosing, mean exercise duration was 407 sec. after placebo and 523 (+28%) and 485 (+ 19%) sec. after TTS NTG and nifedipine SR respectively, while at the 8th hour it was 375 sec. after placebo, and 515 (+ 37%) and 457 (+ 21%) sec. after TTS NTG and nifedipine SR. Exercise duration after verapamil was similar to that after placebo. In comparison with placebo maximal workload and total work performed were significantly higher on TTS NTG and on nifedipine at both times of observation, but no significant differences were seen after verapamil. Peak exercise systolic blood pressure was nearly identical after all the treatments tested. Peak exercise heart rate and pressure rate product were both significantly higher on TTS NTG, as well as on nifedipine, in comparison with placebo, while values after verapamil did not differ from those after placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104125 TI - [Contributions of a genetics department to the study of patients in a pediatric hospital]. PMID- 3104126 TI - [Is chronic bacterial contamination of the small intestine associated with cholestasis in total parenteral feeding?]. PMID- 3104127 TI - Valosin stimulates gastric and exocrine pancreatic secretion and inhibits fasting small intestinal myoelectric activity in the dog. AB - Valosin, a novel 25-amino acid gastrointestinal peptide with N-terminal valine and C-terminal tyrosine, has recently been isolated from porcine upper gut extracts. Its physiologic role is unknown and it does not belong to one of the structurally related gut peptide families. Assuming that valosin may influence gastrointestinal functions, we investigated the effect of high-performance liquid chromatography-pure valosin on gastric and exocrine pancreatic secretion and on the intestinal myoelectric activity in conscious dogs. Intravenous injection of valosin (0.125-1 microgram/kg) dose-dependently increased gastric acid secretion 80-fold over basal, corresponding to 18% of the maximal pentagastrin-induced effect. Pepsin output increased 10-fold over basal (30% of the pentagastrin stimulated secretion). Half-maximal stimulation by pentagastrin could be further increased dose-dependently by simultaneous administration of valosin. Pancreatic bicarbonate secretion was stimulated 11-fold over basal at 1.0 microgram/kg, reaching about 6% of the secretin-induced maximal output, whereas protein secretion increased 12-fold over basal, corresponding to about 55% of the cholecystokinin-induced maximal output. In fasted dogs, spontaneously occurring migrating myoelectric complexes were substantially delayed during infusion of valosin at a dose of 0.2 microgram/kg. These experiments indicate that valosin may represent a novel member of the regulatory gastrointestinal peptides. PMID- 3104128 TI - Biliary excretion of apolipoprotein B by the isolated perfused rat liver. Relationship to receptor-mediated uptake of human low-density lipoprotein and biliary lipid secretion. AB - Since we previously reported that apolipoproteins, the lipid transport proteins of lipoproteins, are present in human bile, we tested the hypothesis that apolipoproteins in bile are derived from circulating lipoproteins and that they are involved in the biliary excretion of lipids. We perfused isolated rat livers with lipoprotein-free solutions and collected bile before and after addition of human low and high density lipoproteins. When human low density lipoprotein was added to solutions perfusing livers isolated from rats previously treated with ethinyl estradiol, a hormone that increases receptor-mediated uptake of low density lipoproteins by hepatocytes, the concentrations in bile of cholesterol and phospholipid, but not bile acids, increased by approximately 25% together with the appearance of small amounts (approximately 1% of the amount perfused) of a metabolized form of human apolipoprotein B in bile. Acetylation of low density lipoprotein, a procedure that prevents this lipoprotein from binding to its receptor on hepatocytes, both abolished the appearance of immunoreactive apolipoprotein B in bile and blocked the increase in biliary cholesterol and phospholipid concentrations. Whereas the addition of a high density lipoprotein to solutions perfusing isolated livers of normal rats was associated with the appearance of small amounts (approximately 1% of the amount perfused) of apolipoproteins A-I and A-II in bile, there were no accompanying changes in the concentrations of biliary lipids. These results suggest that apolipoproteins or their fragments in bile are derived from circulating lipoproteins; in the case of apolipoprotein B, biliary excretion is dependent upon receptor-mediated uptake of low density lipoprotein by the hepatocyte. Our data are also consistent with the hypothesis that certain apolipoproteins may be involved in biliary lipid secretion, although in an as yet unclear manner. PMID- 3104129 TI - Percutaneous endoscopic gastrostomy for gunshot wounds to the oropharynx. PMID- 3104130 TI - Lesion of selected brain areas as a tool for the demonstration of some trace biogenic amines neural pathways. PMID- 3104131 TI - Effects of nitro compounds, isosorbide dinitrate, 5-isosorbide mononitrate and glyceryl trinitrate on Ca-uptake into Ca-stores and Ca-release from Ca-stores in rabbit isolated femoral veins and femoral arteries. AB - In organ bath studies, effects of isosorbide dinitrate (ISDN), 5-isosorbide mononitrate (ISMN), a major metabolite of ISDN, and glyceryl trinitrate (GTN) on Ca-uptake into Ca-stores and Ca-release from Ca-stores were tested in the rabbit isolated femoral veins and femoral arteries. ISDN (10(-4) M) and GTN (10(-4) M) inhibited Ca-uptake in the femoral veins but not in the femoral arteries. The selectivity to the femoral veins was not observed in ISMN (10(-3) M) and GTN (3 X 10(-6) M). All the nitro compounds inhibited Ca-release from Ca-stores more effectively in the femoral veins than in the femoral arteries. The present results may explain the selectivity of the nitro compounds to the femoral veins. PMID- 3104132 TI - Effects of suppression and resumption of shell formation and parathyroid hormone on uterine calcium-binding protein, carbonic anhydrase activity, and intestinal calcium absorption in hens. AB - The calcium absorption and duodenal and uterine vitamin D-dependent calcium binding protein (CaBP-28K) levels were decreased in hens when eggshell calcification was suppressed by premature expulsion of the egg. Nevertheless, these levels remained higher than those of immature pullets or pullets treated with estrogen. The resumption of shell formation by hens which had previously laid soft-shell eggs was associated during calcification of the first egg with increases in intestinal Ca absorption. CaBP concentration, and alkaline phosphatase activity. The increase in uterine CaBP concentration preceded the stage of rapid calcium deposition. Uterine carbonic anhydrase activity was increased by sexual maturity but not consistently by shell formation. Ablation of the parathyroids just before the resumption of shell formation suppressed the increases in duodenal calcium absorption and CaBP concentration elicited by egg calcification. In contrast, the increase in CaBP level was maintained in the uterus of parathyroidectomized hens, in spite of the decreased shell deposition. Previous studies indicated that increased uterine CaBP associated with eggshell calcification is not elicited by vitamin D. The present study confirms this observation and also shows that these changes are not elicited by either PTH or sex steroid hormones. PMID- 3104133 TI - Hormonal control of the intestinal brush border enzyme activities in developing anuran amphibians. II. Effects of glucocorticoids and insulin during experimental metamorphosis. AB - The effects of glucocorticoids (hydrocortisone, dexamethasone) and insulin on enzymatic activities of the intestinal brush border membrane were investigated in an anuran amphibian, Alytes obstetricians, before and during experimental metamorphosis produced by immersion into a thyroxine solution. During experimental metamorphosis, a new epithelium (secondary epithelium) replaces the degenerating primary epithelium. The enzymes studied were three glucidases (maltase, glucoamylase, trehalase) and alkaline phosphatase. In tadpoles reaching the end of premetamorphosis, hormones were injected every day (hydrocortisone, dexamethasone: 25 micrograms/g body wt/day; insulin: 5 mU/g body wt/day, for 3 and occasionally 6 consecutive days. Under such conditions, most of the activities in the primary epithelium increased or remained stable. In animals which completed experimental metamorphosis, the secondary epithelium formed. Hydrocortisone (25 micrograms/g body wt/day) and insulin (5 mU/g body wt/day) treatments significantly decreased the enzymatic activities of the new brush border membrane in animals which received one hydrocortisone and/or insulin injection per day, during 3 consecutive days. Such results, which previously had not been obtained systematically in spontaneously metamorphosing tadpoles (El Maraghi-Ater, Mesnard, and Hourdry (1986). Gen. Comp. Endocrinol. 61, 53-63), emphasize the relative independence of the intestinal metabolism during experimental and spontaneous metamorphosis. PMID- 3104134 TI - Variation in Y chromosome segregation in natural populations of Drosophila melanogaster. AB - Functional variation among Y chromosomes in natural populations of Drosophila melanogaster was assayed by a segregation study. A total of 36 Y chromosomes was extracted and ten generations of replacement backcrossing yielded stocks with Y chromosomes in two different genetic backgrounds. Eleven of the Y chromosomes were from diverse geographic origins, and the remaining 25 were from locally captured flies. Segregation of sexes in adult offspring was scored for the four possible crosses among the two backgrounds with each Y chromosome. Although the design confounds meiotic drive and effects on viability, statistical partitioning of these effects reveals significant variation among lines in Y chromosome segregation. Results are discussed in regards to models of Y-linked segregation and viability effects, which suggest that Y-linked adaptive polymorphism is unlikely. PMID- 3104135 TI - Metabolic flux and fitness. AB - Studies of Escherichia coli under competition for lactose in chemostat cultures have been used to determine the selective effects of variation in the level of the beta-galactoside permease and the beta-galactosidase enzyme. The results determine the adaptive topography of these gene products relative to growth in limiting lactose and enable predictions concerning the selective effects of genetic variants found in natural populations. In the terms of metabolic control theory, the beta-galactosidase enzyme at wild-type-induced levels has a small control coefficient with respect to fitness (C = 0.018), and hence genetic variants resulting in minor changes in enzyme activity have disproportionately small effects on fitness. However, the apparent control coefficient of the beta galactoside permease at wild-type-induced levels is large (C = 0.551), and hence even minor changes in activity affect fitness. Therefore, we predict that genetic polymorphisms in the lacZ gene are subject to less effective selection in natural populations than are those in the lacY gene. The beta-galactoside permease is also less efficient than might be expected, and possible forces resulting in selection for an intermediate optimum level of permease activity are considered. The selective forces that maintain the lactose operon in a regulated state in natural populations are also discussed. PMID- 3104136 TI - Construction of an unstable Ring-X chromosome bearing the autosomal dopa decarboxylase gene in Drosophila melanogaster and analysis of Ddc mosaics. AB - An unstable Ring-X chromosome, Ddc+ -Ring-X carrying a cloned Dopa decarboxylase (Ddc) encoding segment was constructed. The construction involved a double recombination event between the unstable Ring-X, R(1)wvC and a Rod-X chromosome which contained a P-element mediated Ddc+ insert. The resulting Ddc+ -Ring-X chromosome behaves similarly to the parent chromosome with respect to somatic instability. The Ddc+ -Ring-X chromosome was used to generate Ddc mosaics. Analyses of Ddc mosaics revealed that while there was no absolute requirement for the Ddc+ expression in either the epidermis or the nervous system, very large mutant clones did affect the viability of the mosaic. PMID- 3104137 TI - [Integration of the plasmid carrying the genes for tryptophan metabolism of Bacillus mesentericus into the chromosome of Bacillus subtilis]. AB - Integration of several tryptophan operon genes from Bacillus mesentericus into the chromosome of Bac. subtilis was carried out. The genetic material exchange between these two species is usually impossible in the process of transformation, because of poor homology. The integration only took place after the genes of Bac. mesentericus were introduced in Bac. subtilis cells on a hybrid plasmid. Plasmid markers also integrated into the chromosome, together with heterologous DNA. The integration occurred in the region of Bac. subtilis tryptophan operon, which is likely to be due to retained homology between corresponding DNAs. The integration acts occurred during prolonged maintenance of chimeric plasmid in autonomously replicating form. We suggest to designate this phenomenon "retarded homologous recombination". PMID- 3104138 TI - [The type of recombination in Drosophila melanogaster mei-9LI males induced by space flight factors]. AB - Spontaneous male recombination in mei-9LI stock of Drosophila melanogaster having defect in excision repair was shown to take place at early premeiotic stage. Male recombination was registered at all stages of gametogenesis, under the action of acceleration (6-8 g). The frequencies of male recombination at pre- and postmeiotic stages of gametogenesis increased significantly under the effect of space flight factors. PMID- 3104139 TI - [The lack of ability of carcinogens and non-carcinogenic analogs to induce sex linked recessive lethals in Drosophila melanogaster]. AB - The mutagenic activity of two known carcinogens (benzo(a) pyrene and 2 acetylaminofluorene) and that of two structurally closely related but not carcinogenic compounds (pyrene and 4-acetylaminofluorene) was examined by the Muller-5 test for sex-linked recessive lethals (SRL). The chemicals tested were applied to the food medium for larvae of Canton-S Drosophila melanogaster. No statistically significant differences in frequencies of induced SRL were found either within pairs of chemicals or between treated and untreated animals. PMID- 3104140 TI - The nursing process in long-stay care. PMID- 3104141 TI - Vaccinia virus vectors utilizing the beta-galactosidase assay for rapid selection of recombinant viruses and measurement of gene expression. AB - Plasmids were constructed fusing vaccinia transcriptional regulatory sequences (promoters) to the lacZ gene of Escherichia coli. These recombinant plasmids were used to compare relative promoter strengths in transient expression assays and to construct recombinant vaccinia viruses producing beta-galactosidase (beta Gal). Viruses synthesizing beta Gal were determined by utilizing the chromogenic substrate, 5-bromo-4-chloro-3-indoyl-beta-D-galactoside to form blue plaques. A recombinant virus producing beta Gal was then used to select a second recombinant virus. This was accomplished via in vivo recombination replacing the lacZ gene with a sequence coding for the gp85 protein of Friend murine leukemia virus. The recombinant virus was selected by its inability to form blue plaques under appropriate conditions. PMID- 3104142 TI - Cloning of genes related to exo-beta-glucanase production in Saccharomyces cerevisiae: characterization of an exo-beta-glucanase structural gene. AB - The EXG1 gene of Saccharomyces cerevisiae was cloned and identified by complementation of a mutant strain (exg1-2) with highly reduced extracellular exo beta-1,3-glucanase (EXG) activity. Two recombinant plasmids containing an overlapping region of 5.2 kb were isolated from a genomic DNA library and characterized by restriction mapping. The coding region was located by subcloning the original DNA inserts in a 2.7-kb HindIII-XhoI fragment. Exg+ strains and Exg- mutants transformed with yeast multicopy plasmids containing this DNA fragment showed an EXG activity 5- to 20-fold higher than for the untransformed Exg+ wild type (wt) strains. The overproduced EXG had the same enzymic activity on different substrates, and showed the same electrophoretic behaviour on polyacrylamide gels and identical properties upon filtration through Sephacryl S 200 as those of the main EXG from Exg+ wt strains. The EXG1 gene transformed Schizosaccharomyces pombe, yielding extracellular EXG activity which showed cross reactivity with anti-S. cervisiae EXG antibodies. A fragment including only a part of the EXG1 region was subcloned into the integrating vector YIp5, and the resulting plasmid was used to transform an Exg+ strain. Genetic and Southern analysis of several stable Exg- transformants showed that the fragment integrated by homology with the EXG1 locus. The chromosomal DNA fragment into which the plasmid integrated has a restriction pattern identical to that of the fragment on which we had previously identified the putative EXG1 gene. Only one copy of the EXG1 gene per genome was found in several strains tested by Southern analysis. Furthermore, two additional recombinant plasmids sharing a yeast DNA fragment of about 4.1 kb, which partially complements the exg1-2 mutation but which shows no homology with the 2.7-kb fragment containing the EXG1 gene, were also identified in this study. This 4.1-kb DNA fragment does not appear to contain an extragenic suppressor and could be related in some way to EXG production in S. cerevisiae. PMID- 3104143 TI - Heterologous expression in Bacillus subtilis. II. In vitro removal of the attenuator sequence of the Escherichia coli his operon allows expression of the cloned hisG gene in B. subtilis. AB - The promoter-proximal region of the Escherichia coli histidine (his) operon, including the promoter, the attenuator and the hisG gene, as well as the first of the nine structural genes of the his operon, have been cloned in Bacillus subtilis. In this host, the hisG gene could not be expressed because its transcription appeared to be irreversibly terminated at the attenuator (Ferretti et al., 1984). When the attenuator plus various lengths of the two bordering regions were removed, one of the attenuatorless sequences cloned in B. subtilis allowed the progression of transcription and complementation of the corresponding hisA mutation in this Gram-positive host. The deletion removed a 349-bp segment which contained the his attenuator and promoter. In B. subtilis, the productive transcription of the hisG gene started at a site in pAT153 and terminated in pC194. Sequence analysis of the deletion indicates that the E. coli ribosome binding site of the his operon was used for the translation of the E. coli hisG gene mRNA in B. subtilis cells, which can thus grow in the absence of histidine. PMID- 3104144 TI - Differential utilization of Staphylococcus aureus promoter sequences by Escherichia coli and Bacillus subtilis. AB - Promoter-cloning plasmids were constructed and have been used to isolate transcriptionally active DNA fragments from Staphylococcus aureus. The plasmids contain a chloramphenicol acetyltransferase (CAT) gene of Gram-positive (G+) origin which lacks both its promoter and the sequence responsible for CAT inducibility. The ability of S. aureus promoters to direct CAT expression in Escherichia coli and Bacillus subtilis was examined. Two classes of staphylococcal promoter sequences have been obtained. Class I DNA fragments direct CAT expression in S. aureus, B. subtilis, and E. coli, while class II DNA sequences direct CAT expression only in the G+ hosts. PMID- 3104145 TI - Cloning and expression of the isopenicillin N synthetase gene from Penicillium chrysogenum. AB - The isopenicillin N synthetase (IPS) gene from Penicillium chrysogenum was isolated from a recombinant bacteriophage lambda library using the Cephalosporium acremonium IPS (cIPS) gene as a heterologous hybridization probe. The protein coding region of the P. chrysogenum IPS (pIPS) gene was about 74% homologous to the cIPS gene, and the predicted amino acid sequences of the encoded proteins were about 73% homologous. Escherichia coli cells with the pIPS gene contained IPS activity whereas untransformed cells were completely devoid of this enzymatic activity. The transformed cells were also shown to contain an abundant protein accounting for about 10% of total cell protein which reacted strongly with anti cIPS antiserum. PMID- 3104147 TI - Continuing care retirement communities: self-insuring for long-term care. PMID- 3104146 TI - Promoter used by sigma-29 RNA polymerase from Bacillus subtilis. AB - Gene expression during endospore formation by Bacillus subtilis is controlled in part by a sporulation-induced form of RNA polymerase, E sigma 29. The determination of the nucleotide sequences that govern utilization of promoters by E sigma 29 has been limited by the small number of available promoters that are recognized by E sigma 29. In the present report we describe a promoter that is adjacent to the rrnB region of the B. subtilis chromosome and is utilized in vitro and in vivo by E sigma 29. S1 nuclease mapping and dinucleotide priming experiments have been used to determine the start point of transcription. The nucleotide sequences near the -10 and -35 region of this promoter, bvx, are conserved, and resemble sequences at these regions for other promoters that are utilized by E sigma 29. PMID- 3104148 TI - [Dynamics of the fetal-maternal exchange after amniocentesis in pregnancy with Rh incompatibility]. PMID- 3104149 TI - Plasminogen activator content of gynecological tumors and their metastases. AB - The plasminogen activator content of surgically excised gynecological tumors was measured with an azocaseinolytic assay. Ovarian (10 primary, 18 metastases) and uterine (5 primary and 6 metastases) tumors showed similar mean activator activities (21 CTA units/g tissue) mainly of the urokinase type with similar wide variations in each group. About 44% (14 of 32) of the tissues placed in short term organ culture were shown to produce and secrete urokinase activity. Results of the plasminogen activator activity found in the patient tumors or produced by the tumors during culture in the absence or presence of some drugs indicate a wide range of individual variations in sensitivity to these agents. PMID- 3104150 TI - Macroglobulinemia--a review. PMID- 3104151 TI - In vitro addition of thiamin does not restore BFU-E growth in thiamin-responsive anemia syndrome. PMID- 3104152 TI - Relationship between immunodeficiency conditions and AIDS-associated retrovirus (ARV) infection in homosexual men and i.v. drug abusers in the Campania Region. PMID- 3104153 TI - Biochemical parameters to assess viability of erythrocytes stored for transfusional use. PMID- 3104154 TI - Optimizing and stabilizing thrombin activity. PMID- 3104155 TI - Morphologic, cytochemical and immunological profile in T-cell acute lymphoblastic leukemia of childhood. PMID- 3104156 TI - Initial chemotherapy with an age-adjusted CHOP-schedule in non-Hodgkin lymphomas with unfavorable prognosis. A study of the I.G.C.I. PMID- 3104157 TI - Case report of a t(4;11)--associated acute leukemia. PMID- 3104158 TI - Monocytic blast cell crisis and IgG-lambda monoclonal gammopathy in a Ph1 + chronic myelogenous leukemia. Report of a case. PMID- 3104159 TI - Acute malignant myelosclerosis. Evidence for a panmyelotic disturbance of cellular differentiation. PMID- 3104161 TI - Immune status in thalassemia major. PMID- 3104160 TI - Proto-oncogene activation in human hematologic malignancies. PMID- 3104162 TI - Association of beta thalassemia, beta c, alpha thalassemia and mental retardation. PMID- 3104163 TI - More on hypocryoglobulins: a cold agglutinin with cryoprecipitation in a hypotonic medium. PMID- 3104164 TI - A case of thrombotic thrombocytopenic purpura. A search for a definite therapeutic approach. PMID- 3104165 TI - Effects of thymopentin on the anaemia of chronic lymphoproliferative disorders. PMID- 3104166 TI - A rare case of penetrating wound of the skull and brain with contracture of the mandible. PMID- 3104167 TI - Clinical effects of azlocillin--Pharmachim in patients with urinary infections. PMID- 3104168 TI - Haemodynamic changes in renal patients with preserved excretory function of the kidneys. PMID- 3104169 TI - Anticipation in duodenal ulcer--development of the disease in patients with hereditary predisposition. PMID- 3104170 TI - An investigation of stomach and duodenal ulcer based on pathomorphological data for ten years. PMID- 3104171 TI - Body plethysmographic diagnosis of bronchial obstruction. PMID- 3104172 TI - Metric study of the tendons in the first osteofibrous canal under retinaculum extensorum manus. PMID- 3104173 TI - Spontaneous EMG volleys of "bizarre" high- and low-frequency potentials in neuromuscular disorders. PMID- 3104174 TI - Carbohydrate tolerance in android obese subjects. PMID- 3104175 TI - [Effect of S-adenosyl-L-methionine on cerebral monoamine turnover after hypoxia in rats]. AB - The effects of S-Adenosyl-L-methionine (SAMe) on cerebral monoamine turnover at 60 min of reoxygenation after hypoxia (PaO2, 31-35 mmHg) for 15 min were studied in 44 rats anesthetized with nitrous oxide. The accumulations of monoamine metabolites: 3-methoxy 4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined after probenecid. The accumulations of noradrenaline (NA) and dopamine (DA) were also determined after pargyline. In the non-treated group, there was an impairment of degradation of NA to MHPG and of DA to DOPAC or HVA in the control group (no hypoxia). These changes were accompanied by higher levels of NA and DA in the cerebral cortex, hypothalamus and striatum than those of the control group. In the group treated with 100 mg/kg SAMe plus 38 mg/kg mannitol 3 min after the start of reoxygenation, there were no significant changes in these metabolites and amines. Mannitol alone did not cause significant changes. There were no changes in serotonin and 5-HIAA in any of the groups studied. The effects of SAMe were studied in an additional 16 awake rats. MHPG in all regions measured after probenecid in the rats treated with SAMe was higher than that without SAMe. It appears that SAMe ameliorates perturbation of cerebral catecholamine turnover produced by reoxygenation after hypoxia. PMID- 3104177 TI - Did Kenyapithecus utilise stones? AB - Before the hypothesis that Kenyapithecus wickeri used stone tools for breaking open bones becomes widely accepted, we should examine the evidence upon which the original claims were made. In this respect it is concluded that the evidence for utilisation of a stone at Fort Ternan to cause depressed fractures in long bones and antelope skulls does not stand up to scrutiny. Therefore the evidence used in erecting the hypothesis is considered refuted, and it cannot be used as further support of the hypothesis. In other respects the hypothesis that K. wickeri used stones in the manner described is untestable, and it should therefore be dropped from the list of scientific hypotheses concerning Kenyapithecus. PMID- 3104176 TI - Effects of size and locomotor adaptations on the hominid pelvis: evaluation of australopithecine bipedality with a new multivariate method. AB - Three pelves and eight innominate bones belonging to the fossil species, Australopithecus africanus, Australopithecus robustus, Homo erectus, and Homo sapiens, have been studied biometrically and compared with those of recent humans and apes. A new method of logarithmic factorial analysis suppresses both the size effects and the size reference on pelvic proportions. In combination with principal component analysis it allows specializations to be dissociated from allometrical variations. Some morphological differences on the hominid pelvis prove to be mainly allometric. However, the pelvic morphology of australopithecines is clearly differentiated from that of the genus Homo (including H. erectus, OH 28, KNMER 3227). A. africanus (Sts 14, MLD 7, AL 288) is nearer the humans than is A. robustus (SK 50, SK 3155), which appears to be more specialized in the australopithecine lineage. The pelvic morphology of A. africanus, as integrated with the articular pelvic-femoral link, appears to be biometrically equivalent to that of humans. PMID- 3104178 TI - Intestinal permeability changes in rodents: a possible mechanism for degraded carrageenan-induced colitis. AB - Rats and guinea-pigs were treated with degraded carrageenan (50 g/litre in the drinking-water) and their intestinal permeability was studied at weekly intervals over the last 4 wk of the test period by determining the recovery of orally administered tracer doses of [3H]polyethylene glycol (PEG-900) or D-[3H]mannitol in 16-hr urine collections. A freely diffusible dye, Azure A, was administered simultaneously to compensate for non-intestinal factors that could modify renal excretion. Animals were killed after a total treatment period of 5 months for rats and 6 wk for guinea-pigs. After 3 wk of carrageenan treatment, excretion of PEG-900 (expressed as a ratio of the Azure A excretion) in guinea-pigs showed a statistically significant increase over that in the control group. At autopsy, the caeca showed numerous macroscopically visible erosions of the entire mucosal surface and histological examination showed ulcerations largely in the mucosa with abscesses in the crypts. Although no such histological changes were seen in the intestines of the treated rats, even after 5 months, a statistically significant increase in PEG-900 excretion was again found compared with the control group. This increase did not occur when deoxycholate was administered with the carrageenan solution. No effect of carrageenan treatment on mucosal permeability to D-[3H]mannitol was demonstrated in either species. The results suggest that degraded carrageenan-induced colitis could be a result of increased intestinal permeability, since ingestion of this polysaccharide by rats increased PEG-900 absorption without causing mucosal damage. PMID- 3104179 TI - [Measuring gastroesophageal reflux. Quantification using solid state long-term pH measurement]. PMID- 3104180 TI - [Interval therapy in effective treatment of angina pectoris using nitroglycerin patch systems. A controlled study with determination of nitroglycerin plasma levels]. AB - In ten patients with angiographically-documented coronary artery disease, stable angina pectoris and reproducible exercise-induced ST-segment depression, the extent and duration of antiischemic and antianginal effects of transdermal nitroglycerin patches delivering 10 mg/24 hours were investigated according to a double-blind, crossover, placebo-controlled protocol. Exercise testing and blood sampling for determination of nitroglycerin plasma concentrations were carried out at 2.5 and twelve hours after initial application, at 2.5, twelve and 24 hours after renewed application subsequent to a twelve-hour treatment pause as well as at 2.5 hours after application of a third patch (Figure 1). At 2.5 hours after initial application there was a reduction in exercise-induced ST-segment depression from 2.7 mm +/- 0.19 (SEM) to 0.75 +/- 0.2 (-72%; p less than 0.001) (Figure 2). The exercise capacity to onset of 1 mm ST-segment depression increased from 117 Watt X min +/- 34 (SEM) to 361 Watt X min +/- 84 (+210%; p less than 0.001) (Figure 3). At twelve hours, exercise-induced ST-segment depression was reduced only from 2.5 mm +/- 13 to 1.77 +/- 0.2 (-32%; p less than 0.01) and the increase in exercise capacity to onset of 1 mm ST-segment depression was narrowed from 136 Watt X min +/- 28.5 to 215 Watt X min +/- 43 (+59%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104181 TI - Kinetic studies of lymphocytes labeled with indium-111-oxine in patients with malignant lymphoma. PMID- 3104182 TI - Vasopressin decreases total free fatty acids but enhances release of radioactivity from isolated hepatocytes labelled with [3H]arachidonic acid. AB - The short-term effects of vasopressin on free fatty acids and lysophospholipids were investigated in hepatocytes isolated from fed rats. Over the time period 0.25 to 10 min vasopressin decreased the steady-state concentrations of palmitic, stearic and oleic acids measured by gas liquid chromatography in extracts of cells incubated at 0.1 mM extracellular Ca2+. The concentrations of arachidonic and linoleic acids did not change. In hepatocytes labelled with [3H]arachidonic acid and incubated at 1.3 mM extracellular Ca2+ vasopressin or the Ca2+-selective ionophore A23187 increased the rate of accumulation of radioactivity in the incubation medium by 40%. The action of A23187 was dependent on extracellular Ca2+. When hepatocytes labelled with 32Pi were treated with vasopressin, no change in the amounts of [32P]lysophosphatidylethanolamine or [32P]lysophosphatidylcholine was observed. It is concluded that the action of vasopressin on hepatocytes is associated with the release of arachidonic acid or metabolites of arachidonic acid but is not accompanied by a general increase in the steady-state concentrations of free fatty acids and lysophospholipids. PMID- 3104183 TI - Effects of dopaminergic agonists on plasma luteinizing hormone-releasing hormone (LRH) and gonadotropins in man. AB - To try to determine the site and mode of action of dopamine (DA) on the secretion of gonadotropins in humans, 4 series of studies were performed in 19 healthy volunteers (7 healthy males, 5 females in follicular phase and 7 postmenopausal females). The intravenous infusion of DA at the rate of 4 micrograms/kg/min decreased plasma LH levels to 75.9 +/- 3.7 (mean +/- SE)% of the initial levels. The oral administration of 500 mg of levodopa (Dopa) also suppressed the concentration of plasma LH to 73.0 +/- 3.5%, but the pretreatment with two doses of 100 mg each of carbidopa (CD), a peripheral dopa decarboxylase inhibitor, attenuated this suppressing effect of Dopa on LH levels (nadir 82.4 +/- 4.1). Plasma FSH were not significantly altered by these drugs. On the other hand, the concentration of endogenous LRH in peripheral blood remained unchanged throughout the studies. The administration of CD alone had no effect on any of these 3 parameters. These results would suggest the direct suppressing effect of DA on pituitary gonadotrophs, although the modulation at the level of the hypothalamus also cannot be ruled out. PMID- 3104184 TI - The effect of enkephalin analogue on pituitary hormone release in human obesity. AB - To elucidate further the role of opioid systems in the neuroendocrine alterations associated with obesity, we investigated the effect of the synthetic enkephalin analogue DAMME in 11 obese subjects and 10 lean controls. Prolactin responses to DAMME were similar in lean and obese, even in those obese subjects who had absent prolactin responses to insulin-induced hypoglycaemia. The obese showed impaired growth hormone release after both DAMME and insulin-induced hypoglycaemia compared to the lean subjects. The discordance of prolactin responses to DAMME and insulin-induced hypoglycaemia in the obese suggests that altered opioid systems are unlikely to account for the hypothalamic dysfunction present in obesity. PMID- 3104185 TI - Abnormalities in pituitary thyroid axis function tests in patients with paroxysmal supraventricular arrhythmias. AB - The study was carried out on 60 consecutive patients (23 males and 37 females) aged between 20 and 83 years (means +/- SD, 40.7 +/- 16) who arrived at our Cardiologic Unit with paroxysmal supraventricular arrhythmias (PSVA) including junctional paroxysmal tachycardia (n = 32), atrial fibrillation (n = 13), atrial flutter (n = 1), premature beats (n = 13) and with no obvious cardiovascular causes. Serum thyroxine and triiodothyronine were normal in all patients and thyroid scintiscan revealed normal shape and size thyroids without autonomously functioning nodule(s). Thyrotropin (TSH) response to thyrotropin releasing hormone (TRH) was normal in 44 subjects in whom normal serum free T4 (FT4) and free T3 (FT3) levels were measured. Six patients with normal FT4 and FT3 levels did not respond to TRH. Abnormalities in thyrotropin response to TRH were observed in 10 patients all exhibiting increased FT4 or also FT3 levels. Among these, 5 patients did not respond to TRH, whereas the remaining 5 exhibited a blunted TSH response to TRH. These results suggest that only in a small proportion (5/60) of consecutive patients with PSVA it is possible to recognize a status of "occult thyrotoxicosis" on the basis of the combined evaluation of free thyroid hormones and TSH response to TRH. PMID- 3104186 TI - Islet transplantation in experimental diabetes of the rat. XI: In vitro tests on artificial membrane applied in islet transplantation. PMID- 3104188 TI - Good models exist. PMID- 3104187 TI - The histogenesis of angiosarcoma of the face and scalp: an immunohistochemical and ultrastructural study. AB - Thirteen cases of angiosarcoma of the face and scalp have been examined using immunohistochemistry and electron microscopy. Endothelial cell markers have been employed in an immunoperoxidase technique on tissue that has either been routinely processed, periodate-lysine paraformaldehyde fixed (PLP) and cold processed, or fixed in methacarn. A consistent pattern of endothelial cell labeling was only achieved in the PLP fixed tissue. In this fixative the angiosarcomas were factor VIII related antigen negative, Ulex europaeus lectin positive, laminin positive, unlabelled by the monoclonal antibody PAL-E, and positively labelled by the monoclonal antibody EN4. Ultrastructural examination of four cases showed evidence of vascular lumina in all tumours. Weibel-Palade bodies were seen in only one case but three tumours showed some evidence of tight junction formation and marginal folding. Thus, our cell marker studies can be interpreted as consistent with a lymphatic derivation for this type of angiosarcoma but in contra-distinction the ultrastructural studies showed tumour channels with features suggestive of blood vessel differentiation. PMID- 3104189 TI - Patient characteristics predictive of treatment costs on inpatient psychiatric wards. AB - A study to determine patient characteristics that are predictive of treatment costs was conducted at the Neuropsychiatric Institute and Hospital of the University of California, Los Angeles. Using nursing care time utilized and length of stay as measures of resource consumption, the study identified several characteristics, such as age and the presence of medical comorbidities, that are predictive of the costs of delivering care. Besides providing information valuable to administrators for product costing, the results of the study augment recent research demonstrating the inadequacy of relying on diagnosis alone--as is the case for psychiatric services under the current Medicare prospective payment system--to predict resource consumption. PMID- 3104190 TI - Are "real" medical costs really soaring? PMID- 3104191 TI - Interest in Alzheimer's centers growing. PMID- 3104192 TI - RAP researcher defends her proposal. Interview by Myk Cherskov. PMID- 3104193 TI - Battle over RAP DRGs heats up even more. PMID- 3104194 TI - Sibling similarities in the strength and motor performance of undernourished school children. PMID- 3104195 TI - [Opsonophagocytic assay of monoclonal antibodies against Pseudomonas aeruginosa group I strain PA10115]. PMID- 3104196 TI - [Study on the routine method of a short-term transforming test in mammalian cells in vitro for detecting carcinogens and promotors]. PMID- 3104197 TI - Chronic glomerular microangiopathy complicating metastatic carcinoma. AB - Six cases of metastatic carcinoma associated with chronic glomerular microangiopathy and renal failure are reported. All had prominent subendothelial lucent zones and double-contoured glomerular basement membranes. There was no immunohistologic or ultrastructural evidence for immune complex entrapment in glomeruli. By immunohistology, material antigenically related to fibrin or fibrinogen was identified in glomerular basement membranes despite a paucity of typical fibrillar fibrin. Four patients received mitomycin C before the onset of renal disease, and one patient received chemotherapy other than mitomycin C before development of renal failure. One patient had no chemotherapy but was given radiotherapy, which did not include the kidneys in the irradiated field. These six cases emphasize the diverse pathophysiologic mechanisms by which glomerular microangiopathy may arise in metastatic carcinoma. PMID- 3104198 TI - Concurrent presence of two clonal populations in small lymphocytic lymphoma of the lung. AB - In a patient with small lymphocytic proliferation (SLP) involving the right middle and right lower lobes of the lung, immunophenotypic studies showed that the neoplastic lymphoid cells in the right middle lobe expressed kappa light chains, whereas those in the right lower lobe expressed lambda light chains on their surface. Gene rearrangement studies with Southern-blot hybridization confirmed the disparate surface immunoglobulin expression, and showed that the SLPs in the two lobes were derived from separate clones. The findings indicate that even morphologically identical lymphomas in the same organ may be immunophenotypically and genotypically heterogeneous. Our findings demonstrate that immunologic and DNA gene rearrangement analyses may complement each other in the study of lymphomas. This case is unique in that it is the first reported case of the concurrent presence of two immunologically distinct clonal populations in an extranodal site. PMID- 3104199 TI - Newly characterized genetic polymorphism of uropepsinogen group A (PGA) using both isoelectric focusing and immunoblotting. AB - Genetic polymorphism of uropepsinogen group A (PGA) was characterized in human urine using a technique involving both polyacrylamide gel isoelectric focusing and immunoblotting with an anti-PGA antibody. PGA was clearly separable into five fractions, termed I to V in order of decreasing anodal mobility. The most slowly migrating fraction V was composed of F (fast) and/or S (slow) band(s). The population frequencies of the three patterns of fraction V (F, FS, and S) and family studies indicated that PGA V is controlled by a pair of alleles, PGA V*F and PGA V*S, at a single autosomal locus, and that both are codominant. The frequencies of the genes are 0.07 for PGA V*F and 0.93 for PGA V*S. PMID- 3104201 TI - Enteral tube feeding: indications, practices and outcomes. PMID- 3104200 TI - Hunter syndrome: presence of material cross-reacting with antibodies against iduronate sulfatase. AB - Polyclonal antibodies were obtained from rabbits by injection of iduronate sulfatase purified 35,000-fold from human placenta, after elution of the enzyme from sodium dodecyl sulfate (SDS) polyacrylamide gels. The specificity of these antibodies towards iduronate sulfatase was demonstrated by immunoprecipitation of enzyme activity; the level of other lysosomal hydrolases and sulfatases remained constant. Immunoblot of iduronate sulfatase from various human sources showed that the antibody recognises a polypeptide of mol. wt. 72,000 daltons in placenta and serum, and a form of mol. wt. 60,000 daltons in fibroblasts. No immunoprecipitable peptide was found in urine or in the culture medium of fibroblasts. Polypeptides of the same molecular weight were recognised in serum and in fibroblasts of Hunter patients. The presence of altered proteins in these patients was also shown by competition experiments. The addition of Hunter proteins alters the binding of normal enzyme to the antibody. PMID- 3104202 TI - Nitrate therapy for angina pectoris. PMID- 3104203 TI - [Norwegian scabies: parasite-host relations. Pathogenetic considerations]. PMID- 3104204 TI - Transcriptive activity of a hyperploid autosomal arm in Drosophila melanogaster. PMID- 3104205 TI - Diagnosis of intrathoracic tuberculosis by detection of tubercle and/or tubercular antigen (TB Ag) in bronchial aspirate. PMID- 3104206 TI - Inhibition of the intracellular growth of Histoplasma capsulatum by recombinant murine gamma interferon. AB - Recombinant murine gamma interferon as well as lymphokines prepared from immune splenocytes and concanavalin A-stimulated T-cell hybridoma activated normal mouse peritoneal macrophages to inhibit the intracellular growth of Histoplasma capsulatum. The activities of the lymphokine from immune splenocytes and of recombinant murine gamma interferon were neutralized by rabbit anti-murine gamma interferon antibody. The intracellular yeasts were not killed by the interaction even though growth was completely inhibited. PMID- 3104207 TI - Cloning and functional expression of the Coxiella burnetii citrate synthase gene in Escherichia coli. AB - The citrate synthase gene from the obligate intracellular rickettsial parasite Coxiella burnetii was cloned and expressed in Escherichia coli. Transduction into E. coli with a C. burnetii gene library constructed in the cosmid vector pHK17 resulted in the functional complementation of the gltA mutation of E. coli MOB154. A GltA+ clone carrying 16.4 kilobase pairs of C. burnetii DNA and designated pJCC959 was isolated and characterized. Southern hybridization analysis confirmed that the pJCC959 cloned insert consists of C. burnetii DNA and that homology exists with the Rickettsia prowazekii citrate synthase gene. Subcloning analysis with the multicopy expression vector pUC8 revealed that citrate synthase expression was under control of a C. burnetti promoter. In vitro transcription-translation of subclones pLPM20 and pLPM30 established a molecular weight of ca. 46,000 for the monomer form of the cloned enzyme. Transposon Tn5 mutagenesis of pLPM30 defined the coding region to approximately 1.2 kilobase pairs of C. burnetii DNA. Maxicell analysis of selected pLPM30::Tn5 insertion derivatives identified the direction of transcription and the relative translational start and stop sites and substantiated the molecular weight value calculated from the in vitro analysis. Inhibition studies showed that citrate synthase activity in crude cell extracts obtained from strain MOB154 transformed with the cloned C. burnetii gene was markedly inhibited by 4 mM ATP, while 4 mM alpha-ketoglutarate had virtually no effect. These data indicate that the C. burnetii enzyme displays regulatory behavior characteristic of the small gram positive bacterial and eucaryotic enzyme. PMID- 3104208 TI - Immunoglobulin A1 protease types of Neisseria gonorrhoeae and their relationship to auxotype and serovar. AB - Immunoglobulin A1 (IgA1) proteases are extracellular bacterial proteolytic enzymes which correlate with virulence in several species of human pathogens. We report that Neisseria gonorrhoeae produced two distinct types of IgA1 protease, each of which cleaved a different peptide bond in the hinge region of human IgA1. The type of IgA1 protease produced correlated with both nutritional auxotype and outer membrane protein I serovar in this organism. Gonococcal type 1 IgA1 protease was produced primarily by N. gonorrhoeae strains which require arginine, hypoxanthine, and uracil (AHU) and which belong to the protein IA-1 or IA-2 serovar. Most isolates of other auxotypes and serovars produced type 2 IgA1 protease. Although both the AHU auxotype and protein IA serogroup were found to be associated with disseminated gonococcal infection, there was no direct correlation of IgA1 protease type with disseminated or with uncomplicated gonorrhea. PMID- 3104209 TI - Test of the virulence and live-vaccine efficacy of auxotrophic and galE derivatives of Salmonella choleraesuis. AB - Aromatic compound-dependent (aro) derivatives of three mouse-virulent strains of Salmonella choleraesuis (Salmonella cholerae-suis) were constructed and shown to be nonvirulent for mice (intraperitoneal [i.p.] 50% lethal dose [LD50], greater than 5 X 10(6) CFU). A pur derivative, and a thy derivative, each of a different virulent parent, remained moderately virulent (i.p. LD50S for BALB/c mice, ca. 10(5) and 5 X 10(4) CFU, respectively). Tested as live vaccines i.p., the aro strains were ineffective in salmonella-susceptible BALB/c and C57BL/6 mice but were somewhat effective in salmonella-resistant CBA/J mice and in outbred CD-1 mice. The pur and thy strains were effective as live vaccines in BALB/c mice when given in sublethal doses. Two previously isolated nonvirulent galE derivatives of S. choleraesuis (i.p. LD50 in BALB/c mice, greater than 10(6) CFU) were also ineffective as live vaccines in BALB/c and C57BL/6 mice. The main antigenic difference between S. choleraesuis (O-6,7) and S. typhimurium (O-4,12) is in O antigen character, thought to largely determine the specificity of protection in salmonellosis. Paired, nearly isogenic O-6,7 and O-4,12 derivatives were constructed from an aro S. typhimurium strain of proven efficacy as a live vaccine. Used as live vaccines, the O-4,12 member protected BALB/c mice against challenge with virulent S. typhimurium, whereas the O-6,7 member did not protect against virulent S. choleraesuis. However, BALB/c mice vaccinated with the O-6,7 member and mice vaccinated with an aro S. choleraesuis strain were protected against challenge with a moderately virulent (LD50, 5 X 10(4) CFU) O-6,7 derivative of an S. typhimurium strain. PMID- 3104210 TI - The matrix of care: a heuristic for assessment and placement. AB - Policymakers and practioners have attempted to enhance the quality of long-term care, and thereby provide appropriate care, by using the notion of levels of care. This approach assumes that the needs of those requiring long-term care can be easily ordered along a single continuum. This conceptual position, however, has led to confusion with the diagnosis of patient needs and conflicting approaches to assessments of those needs. Invariably problems of patient placement and alternative levels of care result. A more productive approach to the issue of providing appropriate care is to separate physical from psychosocial needs when performing functional assessment and to rearrange them into a matrix. By examining each need separately, and the point at which they overlap in the matrix, more direct assessment can be performed, and specified interventions can be designed. PMID- 3104211 TI - Buffer kinetics in biofiltration. AB - A condition of metabolic alkalosis has been generally observed in patients undergoing regular biofiltration (BF). The aim of this study was to assess buffer kinetics during a dialysis session in five patients regularly treated by BF for 10 months (dialyzer Biospal 3000S, Qb 301; Qd 545; UF 36.76 ml/min; dialysate CH3 COO 38 mEq/L; replacement fluid 1000 ml/h with HCO3 100 mEq/L solution). As usually happens using dialyzers with high surface area and permeability, large HCO3 losses (756 +/- 112 mEq) and CH3COO uptakes (677 +/- 152 mEq) were observed. Acetate plasma levels rose to 10.4 mEq/L, a value potentially dangerous to the cardiovascular system. The dialytic buffer gain (acetate uptake + HCO3 administered - HCO3 loss) was high (230 +/- 137 mEq/dialysis) and excessive for patients' needs. It is therefore very important to reduce either the acetate concentration in dialysate or the amount of reinfused bicarbonate. In view of the plasma acetate levels it is preferable to use a dialysis solution containing less acetate. PMID- 3104212 TI - Acid-base balance and respiratory response during biofiltration with polyacrylonitrile membrane. AB - To further elucidate the mechanisms responsible for the hypoxemia we studied ventilation, pulmonary gas exchanges, blood gas pressures and exchanges of CO2-T, CO2-D and HCO-3 in six patients during AD and BD on 1 m2 cuprophan filter and during BF on 1.2 m2 polyacrylonitrile filter. Blood passing through the dialyzer lost 172.8 mM/h of CO2-T in AD, 149.2 mM/h in BF and gained 25.6 mM/h in BD. In AD VE, VA and PaO2 decreased significantly after 30 and 60 min., in BF for the whole duration of dialysis. PoO2 showed a significant decrease both in AD and BF after 60 min. In AD PaCO2 was significantly reduced after 120 and 180 min. All the above parameters remained unchanged in BD. VCO2 remained unchanged in all. VCO2 and R decreased both in AD and BF. However, when VCO2 was corrected for CO2 loss across the dialyzer, overall CO2 loss (ventilated plus filtered) and R returned to basal values. In AD, HCO-3 and pH fell in the first 120 min., while in BD and BF they increased from the beginning of dialysis. In AD hypoventilation, hypoxemia and inadequate correction of acid-base balance were due to the loss of HCO-3 across the filter. In BF also hypoventilation and hypoxemia were due to the loss of HCO-3 across the filter but the acid-base balance was adequately corrected by HCO-3 reinfusion. In BD, there was HCO-3 gain across the filter which induced a gradual correction of acid-base balance without impairment of ventilation. PMID- 3104213 TI - Acid-base balance during biofiltration. AB - Five patients were shifted from acetate dialysis (AD) to biofiltration (BF); their pre-dialytic acid-base balance (ABB) was re-examined for six months before the start of BF. Samples for ABB were drawn at 0', 30', 60', 120' and 180' during three AD and 1, 2 and 3 hours after them (period A). The same procedure was then repeated two months (period B) and 12 months (period C) after the start of BF. From analysis of the data it is concluded that the correction of AD-acidosis is very rapid during the early two months of BF, but the post-BF ABB may be too alkalotic, with risks if respiratory alkalosis is superimposed. After one year of BF, there were fewer pCO2 falls and pH variations; no more post-BF alkalotic rebounds were observed. PMID- 3104214 TI - Role of MHC class-I antigens and the CD3 complex in the lysis of autologous human tumours by T-cell clones. AB - Peripheral blood lymphocytes (PBL) of 4 patients with malignant effusions were stimulated for 6 days with purified autologous tumour cells, before isolation of the lymphoblasts and cloning by limiting dilution in interleukin-2 (IL-2). Forty five clones were analyzed for cytotoxicity (CTX) against autologous, allogeneic tumour and erythromyeloid K562 cells of known status with respect to expression of major histocompatibility complex (MHC) antigens, estimated by reaction with the W6/32 (anti HLA, -A, -B, -C monomorphic) and TDR 31.1 (anti HLA-DR) monoclonal antibodies (MAb). All 45 clones were CD3+. Twenty-five (56%) of them were cytotoxic for at least one target; 24 were autoreactive (restricted in 7); 17 were alloreactive; 16 were K562 reactive. Under comparable conditions autoreactivity was partially blocked by W6/32 in 12/20 effector:target combinations; alloreactivity in 8/13 and K562 reactivity in 0/14. Modulation of effector cell surface CD3 antigens by OKT3 monitored by flow cytometry reduced autoreactivity in 9/14 combinations, alloreactivity in 2/6 and K562 reactivity in 0/4. W6/32 blocking and T3 modulation of cytotoxicity were almost invariably concordant against the same target. The data suggest that, to accomplish lysis of autologous and allogeneic tumour targets, certain clones require MHC recognition and a functional CD3 complex, while for others with similar target cell repertoires, there is no such requirement. It is possible that T-cell clones responding to a tumour-associated antigen (TAA) in the context of self MHC antigens can also respond to an allogeneic class-I product in the absence of TAA, and/or that aberrant class-I antigen expression on autologous tumours accounts for the alloreactivity. PMID- 3104215 TI - Tumor progression in human malignant melanoma: five stages defined by their antigenic phenotypes. AB - The antigenic profile of melanocytic cells in the course of local and systemic tumor progression of human malignant melanoma was investigated by the reactivity of a panel of monoclonal antibodies (MAbs) in frozen sections of histologically defined melanocytic lesions. Specific antigenic phenotypes made it possible to distinguish 5 groups of lesions which could be ranked in relation to each other due to the sequential acquisition or loss of progression markers. On this basis, a scheme of antigenic changes which accompany the stepwise transformation of normal skin melanocytes into highly malignant metastatic melanoma cells is proposed. The steps of tumor progression identified solely by phenotyping with MAbs were in complete concordance with the concept of melanoma progression derived from histological, statistical and clinical analyses. Furthermore, our finding that the expression of gp89 as well as HLA-DR antigens can be induced by interferon-gamma in vitro provides evidence that immune interferon may play a role in the regulation of genes leading to phenotypic changes in progressing melanoma cells. PMID- 3104216 TI - Monitoring of phenobarbitone in epileptic children. AB - Seventy-five children with different nutritional status, who were receiving phenobarbitone for treatment of various seizure disorders, were monitored for their plasma steady state level, therapeutic efficacy and toxicity. A wide inter individual variation in the steady state level was observed. About 10 percent of them had subtherapeutic level, while nearly 30 percent of them had potentially toxic levels, the remaining were within therapeutic range of 10-25 micrograms/ml. Poor compliance was found to be an important contributing factor for the variations in the level. Steady state levels were significantly higher in children with grade II protein energy malnutrition (PEM) than normally nourished children. A good correlation existed between plasma drug level and therapeutic response in nearly 60 percent of the children. Clinical toxicity was observed in nearly two thirds of the children, sedation and behavioral problems being the most common. The importance of monitoring the drug level is discussed for the proper management of epileptic children. PMID- 3104217 TI - Effects of carnitine administration to multiple injury patients receiving total parenteral nutrition. AB - Blood, urine and tissue concentrations of carnitine have been found to be below the normal values in patients receiving total parenteral nutrition (TPN). It might be postulated that the carnitine deficiency is responsible for the metabolic disturbances observed during TPN. To 20 patients (10 male and 10 female) in a state of coma following multiple injuries or brain injury and submitted to a TPN regimen (hypertonic polycarbohydrate, 7% aminoacid solutions on 10% lipid suspensions), we have administered 3-8 g/day of carnitine i.v. as a single bolus each morning. We have found no increase in cholesterol and triglycerides serum levels and a normalization of pyruvate and lactate serum levels. Our results seem to confirm the importance of carnitine in improving metabolism of the energy-giving substrate in patients receiving TPN. PMID- 3104218 TI - Pharmacokinetics and pharmacological properties of two galenical preparations of glibenclamide, HB419 and HB420, in non insulin-dependent (type 2) diabetes. AB - The pharmacokinetics and pharmacological properties of a new micronized preparation of glibenclamide (HB420, 3.5 mg/tablet) were compared to those of the classical formulation (HB419, 5 mg/tablet) in non insulin-dependent diabetics. In a double-blind cross-over randomized acute study, blood glucose, plasma insulin, C-peptide and glibenclamide levels were determined in 10 patients after a standardized breakfast taken 15 min following the ingestion of 1.1 +/- 0.2 tablets of HB419 or HB420. Plasma glibenclamide levels rose faster, the peak value was higher (637 +/- 154 versus 411 +/- 76 nmol/l, p less than 0.05) and the area under the curve from 0 to 240 min was 35% greater (p less than 0.05) on HB420 than on HB419. Nevertheless, the post-breakfast hormonal and metabolic changes were similar with both preparations. In a single-blind cross-over chronic study, 12 patients were treated during 3 successive 6 to 8-week periods--HB419, HB420, HB419--with glibenclamide at a dose of 1.8 +/- 0.3 tablets/day. While fasting blood glucose concentrations remained unchanged throughout the study, postprandial levels decreased from 10.9 +/- 0.8 mmol/l during the HB419 pre period to 9.2 +/- 0.6 mmol/l during HB420 (p less than 0.02) and rose again up to 10.4 +/- 0.8 mmol/l during the last HB419 period (p less than 0.05). Similarly HbA1c decreased slightly from 7.4 +/- 0.3 to 7.2 +/- 0.4% (NS) and increased again up to 7.8 +/- 0.4% (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104220 TI - Soil contamination by some organic micropollutants related to sewage sludge spreading. AB - The aim of the present publication is to give some information on soil contamination by 4 different micropollutant classes due to sewage sludge spreading. The soil under research shows an accumulation of light molecular weight PAHs and PCBs, DEHP and 4-NP just after spreading, but one month later the concentration of these micropollutant groups fall to the concentration detected just before the sludge spreading. As far as the soil concentration is concerned, only PAHs and PCBs are precipitation dependent. Some test plots, enriched during 10 years with fertilisers, pig-dung or sewage sludges show only an increase of the PAH concentrations of the plots amended with sludges. In the same way, the sewage sludge is chiefly responsible for the increase of PCBs in the soils, but pig-dung seems to contain quantities of these micropollutants which have to be taken into consideration. PMID- 3104221 TI - The routine analysis of some specific isomers of polychlorinated biphenyl congeners in human milk. AB - A mixture of 14 polychlorinated biphenyl (PCB) isomers of various congeners, representing approximately 70% of all human milk PCBs reported in the literature, was made up to identify and approximate their residues in human milk. Individual isomer levels varied from 5 to 103 nanograms per gram of milkfat with the 2,2',4,4',5,5'-hexachlorobiphenyl isomer as the major PCB contaminant of human milk. PCB isomer numbers 74, 118, 153, 138 and 180 made up approximately 75% of all PCBs as measured by this mixture. There was close agreement of total PCB isomer content in breast milk between electron capture gas chromatography and gas chromatographic mass spectrometry determinations. A major interference was encountered however for PCB isomer no. 52, whose residue level in the breast milk was approximately 3 X higher by gas liquid chromatography than by mass spectrometry. PMID- 3104219 TI - A comparative study of the calcification-promoting action of 1,25 (OH)2D3 and calcitonin on the growth cartilage of rats with 1-hydroxyethylidene-1, 1 biphosphonic acid (HEBP)-induced rickets. AB - When HEBP (1-hydroxyethylidene-1, 1-biphosphonic acid) was administered to young rats in large doses over a short period rickets was consistently produced. When HEBP was administered concomitantly with 1,25 (OH)2D3 or calcitonin (CT), calcification appeared in the growth-plate cartilage where there had been an increase in thickness due to the inhibition of calcification. This experiment was done in an attempt to clarify differences in the calcification-promoting mechanisms of 1,25 (OH)2D3 and CT. The serum alkaline phosphatase level was reduced in rats with an accelerated calcification following the administration of 1,25 (OH)2D3, but there was no reduction in the serum alkaline phosphatase level in rats in which the calcification was accelerated by the administration of CT. The mode of appearance of calcification in the growth-plate cartilage by 1,25 (OH)2D3 or CT differed, depending on the time of administration. These results suggest that mechanisms involved in the enhancement of calcification by 1,25 (OH)2D3 and CT differ in cases where rickets are induced by HEBP. PMID- 3104222 TI - Radiation damage repair capacity of a human germ-cell tumour cell line: inhibition by 3-aminobenzamide. AB - The capacity of a human germ-cell tumour line to repair radiation damage has been investigated by means of a clonogenic assay. Dose-rate dependence studies, split dose experiments and experiments designed to measure repair of potentially lethal damage have been performed. The cells showed some ability to repair radiation induced damage in all three types of experiment. An attempt has been made to understand the possible cellular mechanisms of these repair processes by the use of 3-aminobenzamide (3-AB), an agent thought to act by inhibition of ADP ribosylation. 3-AB added 2 h prior to and removed 18 h after irradiation at a non toxic dose to unirradiated cells caused a small but consistent increase in cell kill with acute (150 cGy min-1) irradiation, largely involving a reduction in the shoulder region of the survival curve, but had a greater effect in increasing cell kill at a dose rate of 7.6 cGy min-1 and an even greater effect at a dose rate of 1.6 cGy min-1. When 3-Ab was present 2 h prior to the first dose and between two equal doses in a split-dose experiment, inhibition of split-dose recovery was observed. In addition, some inhibition of potentially lethal damage recovery was observed with 3-AB. A possible role for poly(ADP-ribosylation) is thus implicated in the repair of radiation-induced damage of this human tumour cell line during continuous low dose rate or fractionated radiation schedules, although other effects of 3-AB on respiratory metabolism and/or purine synthesis cannot be eliminated as the cause of the observed inhibitory effects. PMID- 3104223 TI - Feeding difficulties in long-stay patients at nursing homes. Caregiver turnover and caregivers' assessments of duration and difficulty of assisted feeding and amount of food received by the patient. AB - The caregivers from 21 out of 24 nursing homes in the county of Vasterbotten, Sweden, recorded the behaviour at feedings of the patients who were totally dependent on assisted feeding during a 4-week period. The observations were conducted on 214 patients. These patients had a median age of 82 yr. The eating difficulty was predominantly associated with the diagnosis of dementia (n = 110), cerebrovascular disease (n = 30) and Parkinsonism (n = 16). Each patient had different feeders at different meals, with a median of 16-20 feeders for one patient during a 4-week period. Of all assisted feedings, 94% were finished within 20 min. The incidence of feeding refusal was 2%. The degree of feeding difficulty and the amount of food ingested were assessed by the caregivers as fairly constant for each patient. It is reasonable to assume that a patient assignment system for the nurses could improve the eating ability of these patients. PMID- 3104224 TI - Anthropozoonotic role of Brucella abortus. AB - During a severe outbreak of brucellosis in buffaloes, two animal attendants and one Veterinarian contracted Brucella abortus infection. All the three persons developed clinical signs of brucellosis. A high antibody titre against Br. abortus was demonstrated in the sera of these sick individuals. The organism could be isolated from the blood of one patient on tryptose agar at 37 degrees C. Clinical spectrum, chemotherapy and prevention of brucellosis has been discussed. PMID- 3104225 TI - Impact of a rigid, puncture resistant container system upon needlestick injuries. AB - Needlestick injuries in a 720-bed tertiary care hospital were analyzed before and after the introduction of a rigid, puncture resistant, needle disposal system. Following implementation of the system, disposal-related injuries decreased from 0.9 per 100 full-time equivalent employees/year to 0.3 per 100 full-time equivalent employees/year (p less than .005). However, needlesticks associated with procedures (2.2 vs. 4.4 per 100 full-time equivalent employees/year, p less than .0005), and those resulting from loose needles (0.5 vs. 1.9 per 100 full time equivalent employees/year, p less than .0005), increased. Injuries occurring during needle recapping or the carrying of needles were not significantly altered. Total needlestick injuries increased from 6.0 to 8.7 per 100 full-time equivalent employees/year (p less than .0005). We concluded that a rigid, puncture resistant, needle disposal system can reduce disposal-related needlestick injuries, but must also be perceived as convenient to impact substantially upon needlesticks associated with other activities. PMID- 3104226 TI - Immunological study of proteins and mucosubstance in saline soluble human ocular mucus. AB - Proteins and mucosubstance of the saline extract of human ocular mucus were studied by immunological analysis. A minor study was made with human tears for comparison. Immunoelectrophoresis of proteins from these two sources consistently revealed similar characteristic gel patterns. Proteins were found as the major constituents of both samples. However, more mucosubstance was present in the saline extract of human ocular mucus than in tears. Seventeen proteins were identified in the mucus extract. Albumin, IgA, and lactoferrin appeared to be the three major proteins, while lysozyme, lactoferrin, tear prealbumin, and ocular mucoisolate were tear and ocular mucus specific. Although saline soluble mucoisolate is complex in structure, it seemed to resist electrical dissociation, producing only one major precipitation line along with a line of IgA during immunoelectrophoresis. The ocular mucoisolate accounted for about 12% of the saline extractable proteins of human ocular mucus. PMID- 3104227 TI - Synthesis and secretion of glycosaminoglycans in cultured retinal pigment epithelium. AB - The synthesis and secretion of glycosaminoglycans (GAGs) in primary cultures of feline retinal pigment epithelium (RPE) was measured. After 14 days in culture, the cells were incubated for 3 days with media containing 20 microCi/ml 35SO4 and 10 microCi/ml [3H]-glucosamine. The GAGs were precipitated from the media and cell layer with cetylpyridinium chloride and ethanol, separated in 0.1 M Ba acetate by cellulose acetate electrophoresis, visualized by Alcian blue staining and fluorography, and quantitated by scanning densitometry and liquid scintillation counting. The predominant radioactively-labeled GAG secreted into the media by RPE cultures was chondroitin sulfate (CS), which accounted for 63% of the 35SO4, and 54% of the 3H incorporated. Radioactively-labeled heparan sulfate (HS), dermatan sulfate (DS), and hyaluronic acid (HA) were also identified in the media. Heparan sulfate accounted for 24% of the 35SO4 and 22% of the 3H, DS contained 13% of the 35SO4 and 7% of the 3H, and HA accounted for 17% of the 3H incorporated into the media GAGs. In contrast, fibroblast cultures secreted primarily HA, which accounted for 84% of the 3H in the media GAGs. The profile of GAGs retained by the cell layer was different from that of the secreted GAGs. The predominant radioactively-labeled GAG associated with the cell layer was HS. This GAG contained 54% of the 35SO4, and 52% of the 3H incorporated into cell layer GAGs. Dermatan sulfate contained 23% of the 35SO4, and 23% of the 3H, while CS accounted for 23% of the 35SO4, and 18% of the 3H incorporated into cell layer GAGs. The remaining 7% of the incorporated 3H was associated with HA. Total GAG profiles were determined for primary cultures of feline RPE by Alcian blue staining, and compared with those of freshly isolated cell samples. The GAG profiles were similar in cultured and freshly-isolated samples; however, the percentage of HS in the freshly-isolated samples was about twice as high as the percentage of HS in cultured samples, while the proportion of DS in cultured samples was higher than in freshly-isolated samples. This study demonstrates that the profile of radioactively-labeled GAGs secreted by primary cultures of feline RPE is distinct from that retained by the cell layer. In addition, the total GAG profile of cultured RPE is similar, but not identical, to that of freshly isolated cells. PMID- 3104228 TI - Fluorescence light microscopy of F-actin in retinal rods and glial cells. AB - The actin cytoskeleton of rod photoreceptors and glial cells in toad retina has been directly viewed using fluorescence microscopy of cells labeled with a potent phallotoxin that specifically binds to F-actin. The three-dimensional organization of this cytoskeletal protein consists of actin filaments, which course through the inner segment and end at the tips of the calycal processes surrounding the base of the outer segment. A transverse layer of actin staining is also observed at the base of rod outer segments in the region where new discs are formed. At the level of the external limiting membrane, evidence has been found for rings of actin within the glial cells that surround the photoreceptors. These actin rings form a structural meshwork in which photoreceptor cells are embedded. PMID- 3104229 TI - Chronic cholecystitis. An analysis of diagnostic strategies. AB - To define the optimal diagnostic approach for suspected chronic cholecystitis comprehensive management strategies were developed. Using a computer model, the frequency of appropriate surgery, inappropriate surgery, complications, death, and medical costs were compared in populations of patients with various disease prevalences. The optimal strategy began with ultrasonography, followed by an oral cholecystogram when the ultrasonogram was inconclusive. Oral cholecystogram also was employed when additional diagnostic studies failed to provide another explanation for the patient's symptoms. Compared with strategies using only ultrasonography or oral cholecystography, the combination strategy lowered the frequency of inappropriate surgery from 7.1 to 4.4% and direct medical costs from $1,877 to $1,766 per patient in a population with a 20% prevalence of chronic cholecystitis. The differences persisted at higher prevalences of cholecystitis and when sensitivities and specificities of the tests were varied over ranges reported in the literature. Diagnostic accuracy and direct medical costs could be improved by a more frequent interpretation of subtle abnormal ultrasonographic findings as inconclusive and by a more liberal use of oral cholecystography. This analysis demonstrates that a strategy combining ultrasonography and oral cholecystography is superior to the use of either test alone and is cost efficient. PMID- 3104230 TI - Effect of multiple intravenous injections of diatrizoate on iodine concentrations and osmolality. An experimental study in rabbits. AB - Multiple intravenous injections of contrast media are used in radiology, but information regarding corresponding changes in the serum iodine concentrations and osmolality is lacking. We measured the changes in serum iodine concentration and serum osmolality in rabbits after a series of intravenous injections of contrast media. Hypaque-76 (1 cc/kg) was injected intravenously in awake rabbits at 10-minute intervals for 1 hour and arterial blood sampled at midpoint times between injections. During the 1-hour period of seven serial injections, mean serum iodine concentration at 5 minutes was 2.3 mg I/cc (+/- 0.1 SEM, n = 14); at 35 minutes, 5.1 mg I/cc (+/- 0.2); and at 65 minutes, 6.7 mg I/cc (+/- 0.4). The mean peak concentration was 6.8 mg I/cc (+/- 0.4). Serum osmolality underwent a mean increase of 16 mosm/kg during the injection period. Hypertonic mannitol injections produced a smaller increase in osmolality (10 mosm/kg). Isotonic saline injections in control animals produced no change in osmolality. PMID- 3104231 TI - Hepatobiliary magnetic resonance contrast agents assessed by gadolinium-153 scintigraphy. AB - A simple method to test new gadolinium complexes potentially useful as enhancement agents for magnetic resonance imaging was developed. Healthy rats underwent scintigraphy with two potential hepatobiliary agents, diethyl IDA and diisopropyl IDA complexed with gadolinium-153. Control products included 153Gd DTPA, 153GdCl3 and technetium-99m diethyl IDA. As shown scintigraphically, 153Gd IDA complexes were partially excreted by urinary and hepatobiliary excretion early after administration. These findings paralleled significant reduction in 1H T1 values of excised livers. However, these agents exhibited prolonged 153Gd whole-body retention. The prolonged tissue distribution of 153Gd activity in animals given 153Gd diethyl IDA did not differ significantly from that observed in animals given GdCl3, and could be attributed to chemical instability or reticuloendothelial uptake. The scintigraphic method permits screening of gadolinium complexes in animals by showing mass balance, kinetics, distribution, and effective stability. Biologic effects of tracer or pharmacologic levels can be compared with those of carrier-free and carrier-added pharmaceuticals. PMID- 3104232 TI - Withholding nutrition and mistrusting nurturance: the vocabulary of In re Conroy. PMID- 3104234 TI - Long-term care for the elderly--who goes where? PMID- 3104233 TI - The use of absorbable suture: morphological findings in a newborn three months after coarctation repair. AB - The macroscopic and histological findings in a case of surgical repair of aortic coarctation in a newborn, performed using polydioxanone, a monofilament absorbable suture material, are reported. The persistence of suture material three months after surgery, the lack of severe inflammatory changes, calcification and elastic disruption of the arterial wall, confirm previous experimental data. For these characteristics, the use of polydioxanone in the repair of aortic coarctation in newborns is suggested, in order to avoid recoarctation, the most frequent complication of this surgical therapy. PMID- 3104235 TI - Quality circles in the hospital setting: their current status and potential for the future. PMID- 3104236 TI - Selling health promotion to corporate America: uses and abuses of the economic argument. AB - Economic considerations constitute a significant factor in businesses' interest in adopting health promotion (HP) programs and in the wellness community's attempts to sell such programming to business. Substantial elements of both the business and wellness communities believe that HP programs are financially profitable, in addition to, and as a result of, improving employees' health. Examination of the foundation of this belief, however, leads to the conclusion that underlying analyses have been technically flawed and have ignored important costs of HP programs. This article discusses the limitations of these analyses and outlines the framework of a model that could provide a sound assessment of the economics of workplace HP programs. In general, it is expected that resultant analyses would find less direct profit potential in workplace HP programs but would emphasize the cost-effectiveness of many such efforts. The latter would force recognition that health, and not profit, is the principal benefit of health promotion programming. The distinction between the cost-effectiveness and cost saving potential of health promotion is one that all interested parties should master. PMID- 3104237 TI - Medical information systems for home care. PMID- 3104238 TI - The 4 h/24 h 99mTc-MDP whole body retention: a new index of bone pathology. AB - A simple technique for determining the whole body retention of 99mTc labeled methylene diphosphonate (MDP) at 4-h and 24-h was applied to 28 adult patients (22 prostate cancer, 6 osteoporosis). Following administration of 20 mCi (740 MBq) 99mTc-MDP, a qualitative scintigram was performed and whole body retention was recorded at 4 and 24 h. The prostate cancer patients all had positive bone scintigrams, and of this group, 7 were in relapse and 15 in remission on chemotherapy. The osteoporotic groups whole body retention values were determined prior to the initiation of drug therapy. Mean percent whole body retention values were significantly greater at 4 and 24 h for the cancer patients in relapse relative to both the prostate cancer patients in remission and the osteoporotics: 4-h%/24-h%; equals 74.3/60.2, 57.5/33.5, and 48.0/30.3, respectively. The whole body retention values of the latter two groups, however, were only significantly different at 4-h. An additional index of skeletal pathology was developed by combining the 4-h/24-h values to calculate the biological half time (t1/2b) for this time period using a single exponential model. Again the cancer patients in relapse exhibited a significantly longer half time relative to those in remission and the osteoporotics (70.4 vs 25.7 h and 29.2 h, respectively). The combination of 4 and 24-h whole body retention values with the associated t1/2b has potential for following and classifying patients during the course of their skeletal disease. These values have been shown to be especially valuable with cancer patients with metastatic disease. PMID- 3104239 TI - Structural and functional characterization of a canine minor glycosylated hemoglobin, Hb Can AIc. AB - Structural and functional studies of minor glycosylated hemoglobins in non-human mammals have been very few. Therefore, we attempted further characterization of a canine glycosylated hemoglobin (tentatively designated as Hb Can AIc) which had been isolated by Bio-Rex 70 chromatography (Enoki, Y. et al. (1982) Hemoglobin 6, 143-151). After isolation of the constituent subunits by hybridization mercuration technique, we found by peptide mapping that the structural modification was confined in amino-termini of the beta subunits in which glycosyl ketoamine linkage was also shown to be localized by thiobarbituric acid reaction. Compared with the major hemoglobin (Hb Can A0), Hb Can AIc was characterized by such functional properties as a slightly lower oxygen affinity and a markedly reduced response to the allosteric effects of carbon dioxide and organic phosphates. The anion and H+ Bohr effects were not different from those in Hb Can A0. All these facts support that this hemoglobin is a canine counterpart of Hb AIc. PMID- 3104240 TI - A cross-sectional cost/benefit audit in a hospital obesity clinic. AB - A cross-sectional survey was made of the 25 men and 127 women attending a hospital obesity clinic over a period of 6 weeks. Among the men the mean (+/- s.d.) age was 37 (+/- 14) years, weight 115.2 (+/- 25.4) kg, height 1.70 (+/- 0.09) m, and Quetelet's index 39.6 (+/- 6.4) kg/m2. Among the women the corresponding values were 41 (+/- 15) years, 102.2 (+/- 22.3) kg, 1.60 (+/- 0.07) m, and 40.3 (+/- 9.2) kg/m2. The most common reasons for wishing to lose weight among both men and women was to improve appearance, shortness of breath and pain in weight-bearing joints. About one-third of the patients tested had raised fasting plasma triglyceride levels. Only one had tests indicating hypothyroidism, and two were hyperthyroid. None of these characteristics predicted how long the patient would continue to attend the clinic. Weight loss was calculated according to the duration of attendance at the clinic, and the method of treatment. Two men and 15 women were treated by jaw-wiring, and the remainder by dietary advice alone. No anorectic or thermogenic drugs were used. Among men treated by diet alone the mean weight loss after 1-3 months, 4-6 months, 7-12 months and greater than or equal to 13 months attendance was 5.0 +/- 6.2 kg, 12.4 +/- 11.0 kg, 12.4 +/- 10.2 kg and 13.0 +/- 5.2 kg respectively. Two men treated by jaw-wiring had lost 23.9 and 57.9 kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104241 TI - Differential expression of the HLA-DR genes in various melanoma cell lines treated with interferon-gamma: methylation of the HLA-DR alpha gene in these lines is not correlated with its expression. AB - Melanoma cell lines treated with or without interferon-gamma were tested for the presence of DR alpha mRNA and protein. The six lines examined fell into three general categories: two that expressed high levels of DR alpha mRNA and protein before and after interferon-gamma treatment, one that expressed very low levels before treatment with interferon-gamma, but was induced to express high levels after interferon-gamma treatment, and three that expressed very low levels before treatment, and were only slightly inducible after treatment with interferon gamma. The presence of DR-alpha protein on the melanoma cell surface was always positively correlated with the presence of DR alpha mRNA in the cells. Furthermore, in the cell line that was interferon-gamma-inducible, the time at which DR alpha mRNA and protein appeared and the doses of interferon-gamma needed to induce this appearance were directly correlated. Methylation patterns of the DR alpha gene in these cell lines were also studied in order to determine whether the degree of DR alpha gene methylation among the lines correlated with expression of the gene. Digestion of DNA with the restriction enzyme MspI, which recognizes the sequence 5'CCGG3' and 5'CmCGG3', led to the appearance of a 3.1 kb band from all lines tested. Hpa II digestion, which recognizes 5'CCGG3', but not 5'CmCGG3', led to the appearance of 3.1, 4.4, and 6.7 kb bands in all lines tested except for DUMEL 8, which showed only the 3.1 kb band. Interestingly, DUMEL 8 expressed very low levels of DR alpha mRNA and protein before and after interferon-gamma treatment. We conclude that interferon-gamma has a regulatory effect on DR alpha genes of various melanoma cell lines to varying degrees. This may reflect an effect of interferon-gamma on certain subpopulations of melanocytes in vivo. Our data also indicate that partial methylation of the DR alpha gene does not inhibit its expression. Furthermore, interferon-gamma does not appear to induce expression of the DR gene by altering methylation patterns within the region recognized by our probe. PMID- 3104242 TI - Feasibility of non-surgical definitive management of anal canal carcinoma. AB - The management of anal canal carcinoma has evolved over the last decade, with the combination of radiotherapy (RT) and chemotherapy (CT) offering a definitive alternative to surgery or RT alone. Twenty-two patients with basaloid/cloacogenic/squamous cell carcinoma of the anal (13 with T3-T4 lesions), were treated with synchronous RT (30.00 to 45.00 Gy in 3 1/2 to 5 weeks) and CT X 2 courses (Mitomycin C 15 mg/m2 I.V. bolus + 96 hours 5FU infusion). This regimen differed from the conventional Nigro regimen in that higher doses of RT and 2 courses of Mitomycin C were used and both CT courses were given synchronously with RT. Three patients with residual disease were salvaged with an additional course of CT and local RT, without surgery. Acute side effects including perineal dermatitis, diarrhea, leukopenia, and thrombocytopenia were reversible or transient. Twenty patients are alive and free of disease 17 to 62 months (median 45 months) following initiation of treatment. Two patients died at 7 months without evidence of disease at autopsy. These results compare favorably with other series employing RT alone, AP resection alone, and to those employing similar CT-RT regimens as well, in terms of disease-free survival rate (100%), complete response rate (19/22 or 86%), salvage rate without surgery (3/3), and acceptable morbidity. These results may be attributed to an optimal balance of RT and CT doses and refinements in RT technique which are detailed in our report. PMID- 3104243 TI - Heterogeneity of stage II glottic carcinoma and its therapeutic implications. AB - The heterogeneity of glottic carcinoma results in variable loco-regional control probabilities from 40 to 80%. These widely different results may be due to two prognostic parameters of the tumor: the mobility of the vocal cord and the volume of the tumor. On the other hand radiation dose and technique may influence the treatment results. Stringent work-up has been prospectively undertaken in 156 patients with Stage II glottic carcinoma since 1974 through 1983 in the Academic Hospital of the Free University in Amsterdam. Several subgroups were defined from the beginning to indicate one or both of these prognostic factors. All were treated with a high quality accurate radiation therapy program delivering high dose to all patients with worse prognostic factors and even higher dosages to voluminous tumors with impaired mobility of a cord or slowly regressing tumors. The latter was individually judged for each patient towards the end of the treatment period. The loco-regional control probability of around 80% for all the subgroups irrespective of the prognostic factors indicate that the heterogeneity of Stage II glottic cancer may be influenced by high dosages of quality controlled radiotherapy. Thus results hitherto reported in literature may be further improved by the dose-schedules outlined here. PMID- 3104244 TI - Intraoperative and external beam irradiation +/- 5-FU for locally advanced pancreatic cancer. AB - Because of the poor local control rates obtained with external beam irradiation +/- chemotherapy for locally advanced pancreatic cancer, our institution has used intraoperative radiation therapy (IORT) with electrons to deliver a single "boost" dose of radiation in 52 patients with biopsy-proven adenocarcinoma (primary, unresectable-49; primary, residual-2; and recurrent, unresectable-1). Patients received 4500-5000 rad of fractionated external beam irradiation and an IORT dose of 1750 rad (2 patients) or 2000 rad (50 patients). Acute and chronic tolerance have been acceptable. Documented local progression within either the external beam or IORT fields has been infrequent (3 of 42 evaluable patients or 7%), but there has been little, if any, change in median or long-term survival from that seen in external beam series. This is probably because of a high incidence of liver and peritoneal metastases with pancreatic cancer. A phase II pilot trial, which combines upper or total abdominal irradiation and infusion 5 FU with tumor nodal irradiation plus IORT, is in progress in our institution to evaluate tolerance and the relative incidence of abdominal failures. PMID- 3104245 TI - Carcinoma of the extrahepatic biliary system--results of primary and adjuvant radiotherapy. AB - From 1975-1983, 20 patients with primary carcinomas of the gallbladder (GB) or extrahepatic bile ducts (EHBD) were irradiated with curative intent at the Washington University Medical Center and affiliated hospitals. Of the 17 patients with EHBD cancer, one received adjuvant irradiation after gross resection with positive microscopic margins. All others received primary irradiation for unresectable tumors, or for gross residual tumor after incomplete resection. The 8 patients receiving Ir192 implant in addition to external radiation showed improved (p = 0.06) survival compared to the 9 receiving external only: median 15 months (range 1.5-34 + months) versus 7 months (range 2.5-21 months). Failures were predominantly local-regional, with only one patient showing metastatic spread without known local-regional tumor. Adjuvant radiation therapy was given after cholecystectomy to 3 patients with GB cancers showing tumor extension beyond the serosa or to regional lymphatics. Of these, two survived at 22+ and 27+ months; the third died of local recurrence at 5 1/2 months. Although numbers are small, these results appear to support the use of adjuvant radiotherapy in patients with microscopic residual GB cancer. Aggressive local and regional radiotherapy can add to the quality and length of survival in both patient groups, that is, those with resectable lesions with high likelihood of microscopic residual, and also those with unresectable or gross residual disease after surgery. PMID- 3104246 TI - Prevention of heterotopic bone formation with early post operative irradiation in high risk patients undergoing total hip arthroplasty: comparison of 10.00 Gy vs 20.00 Gy schedules. AB - Prior studies have demonstrated the effectiveness of postoperative radiation therapy (RT) to the hip area following total hip replacement (THR) surgery in preventing the development of heterotopic bone formation in patients considered to be at high risk for development of this complication. Previously, patients received 20.00 Gy in 10 fractions (fx) over 2 weeks, beginning as soon postop as medically feasible (usually post-op day 2). In an effort to reduce hospital stay and risk of secondary malignancy, a prospective treatment program was initiated April 1982 using a reduced dose of 10.00 Gy in 5 fx over 5-7 days. As of February 1984, 46 consecutive hips determined to be at high risk were treated with this reduced dose. Prior studies have demonstrated that heterotopic bone is always radiographically evident by 8 weeks. Of the 46 hips, 41 had been evaluated with the minimum required 8 week follow-up X ray. Twenty-five of these hips, 61%, had a mean long term follow-up of 12 months. Our historical control group, consisting of 54 consecutive high risk post-THR's, was shown to have a 68.5% incidence of heterotopic bone. The 20.00 Gy group, when RT was started by post-op day 5, demonstrated a 3.2% incidence, compared to 4.9% in the 10.00 Gy group. Complication rates were also comparable in the two RT groups, 19.4% and 7.3% respectively; 10.00 Gy is apparently as effective as 20.00 Gy in preventing heterotopic bone formation in high risk post-THR patients. PMID- 3104247 TI - Response of the mediastinal and thoracic viscera of the dog to intraoperative radiation therapy (IORT). AB - IORT may be a potentially useful adjunctive treatment combined with surgery and/or external beam irradiation in treating locally advanced lung and esophageal tumors. To begin investigation of this modality, the tolerance of intact mediastinal structures to IORT was studied using adult American Foxhounds (wt. 25 30 kg). Groups of six animals received IORT to doses of 20, 30, or 40 Gy to two separate intrathoracic ports, using 9 MeV electrons to treat a portion of the collapsed right upper lobe, and 12 MeV electrons to treat the mediastinal structures. A group of three dogs received thoracotomy with sham irradiation. Two dogs from each treatment dose group, as well as one sham-irradiated control, were sacrificed electively at 1, 3, and 12 months following IORT. There were no acute nor late IORT related mortalities. Post-operative weight loss was minimal (average 4.5% of pre-operative weight) for all dogs. Serial esophagrams showed no inflammation or ulceration. No cardiac nor pulmonary changes were noted clinically. At autopsy, the irradiated lung showed evidence of acute pneumonitis at 1 month with progressive fibrosis at 3 months and 1 year. Esophageal reactions were minimal, with only two dogs (one 30 Gy and one 40 Gy) demonstrating histologically confirmed esophagitis at 1 month. Tracheal changes were minimal. Cardiac damage was evident in the right atrial tissues. In several dogs, this cardiac damage ranged from myocardial vascular changes to frank ischemic necrosis noted at 1 and 3 months, and dense fibrosis at 1 year. The phrenic nerves showed normal function, but had evidence of perineural fibrosis. The large vessels demonstrated only mild histologic evidence of irradiation. The results of this large animal study suggest that intact mediastinal structures will tolerate small volume IORT to doses of 20 Gy without significant clinical sequellae. Although the histologic changes in the right atrium and contralateral lung are worrisome, no cardiac nor pulmonary problems arose over the 1 year follow-up. Irradiation of the contralateral lung and other sensitive structures can be reduced by careful selection of electron beam energy and use of custom lead shielding. PMID- 3104248 TI - Combined surgery and radiation in endometrial carcinoma: an analysis of prognostic factors. AB - From 1969 to 1979, 300 patients with the diagnosis of endometrial cancer operated elsewhere were referred for treatment to the Department of Radiation Oncology at Memorial Sloan-Kettering Cancer Center. All the patients were staged according to FIGO classification. One hundred and seventy-three patients were Stage IA, 105 patients were Stage IB, and 22 patients were Stage II. Within Stage IA, 141 patients had well differentiated tumor (G1), 20 had moderately well differentiated tumor (G2), and 12 patients had poorly differentiated (G3). One hundred and thirty-three patients had superficial myometrial invasion and 40 patients had deep myometrial invasion. Within Stage IB, 69 patients had G1 tumor, 23 had G2, and 13 had G3 tumors. Seventy-four patients in this group had superficial myometrial invasion and 31 patients had deep myometrial invasion. Two hundred and eighty-three patients had adenocarcinoma, 13 patients had adenoacanthoma, 4 patients had adenosquamous and other histological types. All of the patients received combined surgery (total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) and radiation. The radiation treatments consisted of external pelvic radiation and intravaginal vault radiation. External pelvic radiation was delivered with a megavoltage apparatus for a total dose of 4,000 cGy in 4 weeks preoperatively (47 patients) or postoperatively (105 patients) in patients presenting with high grade (G2,G3), more than 1/3 myometrial invasion, Stage II and extrauterine extension of disease at surgery. All patients received in addition, postoperative intravaginal vault irradiation consisting of 2100 cGy in 3 fractions over 4 weeks with a high dose rate remote afterloading technique. The follow-up in these patients ranged from 5-14 years. Survival data was calculated according to Kaplan-Meier Method and Cox regression multivariate analysis to identify the prognostic factors. The 10-year survival rate in Stage IA was 91%; in Stage IB 75%; and in Stage II it was 71%. Eleven patients (4%) developed recurrent disease with either local and/or distant metastasis. Nine-percent of the patients developed mild to moderate complications which resolved with conservative treatment. Patients with gross extra-uterine pelvic extension of disease had a poor survival compared with those presenting with microscopic involvement (40% vs. 80% at 5-years). No statistically significant difference in survival was observed between patients who received either preoperative or postoperative external pelvic irradiation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3104249 TI - Radiotherapy with or without misonidazole for patients with stage IIIB or stage IVA squamous cell carcinoma of the uterine cervix: preliminary report of a Radiation Therapy Oncology Group randomized trial. AB - Between August 1980 and November 1984, 119 patients with FIGO Stage IIIB or IVA squamous cell carcinoma of the uterine cervix were randomized to receive radiation therapy (4600 cGy pelvis plus 1000 cGy parametrial boost) followed by intracavitary or external boost to the primary with or without misonidazole (MISO) (400 mg/m2 daily 2 to 4 hours prior to radiation therapy). Patients in the two treatment groups were evenly distributed with respect to stratification variables including stage, Karnofsky Performance score, and positivity of para aortic nodes. Eighty-nine percent of patients had Stage IIIB disease and 88% had a Karnofsky score of 80 or better. Seventy-five percent of patients treated with radiation therapy alone and 79% of patients treated with radiation therapy plus MISO received a boost via intracavitary application. Life threatening (Grade 4) complications occurred in 5 patients receiving radiation therapy alone and one patient receiving radiation therapy plus MISO. MISO toxicity (Grade 3) was limited to severe nausea and vomiting in two patients. With 119 evaluable patients and a median follow-up of 33 months, 64% of patients receiving radiation therapy alone are alive at 18 months compared with 54% for patients assigned to radiation therapy plus MISO. The median survival for patients treated with radiation therapy alone and radiation therapy plus MISO was 1.9 years and 1.6 respectively. At this point in the study the difference in survival is inconsistent with the hypothesis of an improvement associated with MISO. There have been 23 deaths among the 49 patients treated with radiation therapy plus MISO who have been followed for at least 18 months compared with 17 deaths in 48 patients treated with radiation therapy alone. The chance of observing this number of deaths with radiation therapy plus MISO if the addition of MISO improves survival by 10 to 20% is 0.003 and less than 0.001, respectively. The addition of MISO to radiation failed to improve survival for these patients. The results cannot be explained by an uncharacteristically high survival on the radiation therapy alone arm or by an imbalance in the distribution of prognostic factors. Local-regional control remains a problem in the management of patients with advanced cervical carcinoma. More effective and less toxic radiosensitizing agents are needed. PMID- 3104250 TI - Increase in tumor pO2 by perfluorochemicals and carbogen. AB - The effects of perfluorochemicals (Fluosol-DA) in combination with carbogen (95% O2 and 5% CO2) breathing on the tumor pO2 was investigated. The pO2 in RIF-1 tumors grown in the leg of C3H mice was determined by polarographic method using oxygen microelectrodes with diameters of 50-60 micron. The average and median pO2 in the control RIF-1 tumors was about 13 mm Hg and 6 mm Hg, respectively. Carbogen breathing alone could cause a significant increase in pO2 in some tumors and Fluosol-DA injection (i.v.) alone caused a slight change in tumor pO2. When the animals were treated with both Fluosol-DA injection and carbogen breathing, the pO2 markedly increased in most of the tumors resulting in an average and median tumor pO2 of 80 mm Hg and 60 mm Hg, respectively. Such an increase in tumor pO2 may account for the previous observations by us and others that the response of experimental tumors to radiation could be markedly increased by treating the tumor-bearing animals with carbogen and Fluosol-DA. PMID- 3104251 TI - A bleeding disorder (von Willebrand's disease) in a Himalayan cat. AB - A bleeding disorder (von Willebrand's disease) was diagnosed in a 9-year-old male Himalayan cat examined because of persistent oral bleeding after routine dental extraction. Bleeding subsided after empirical treatment, which included prednisolone, vitamin K1, and transfusion of fresh blood, but recurred spontaneously after 8 months of apparent good health. Pertinent results of routine laboratory testing included an inconstant prolongation of the activated partial thromboplastin time and recurring iron-deficiency anemia. Assays of specific coagulation factors revealed low factor VIII coagulant activity and undetectable factor VIII-related antigen, a pattern considered to be diagnostic of von Willebrand's disease. This condition, not previously reported in a cat, should be included in the differential diagnosis when cats are examined because of abnormal bleeding. PMID- 3104252 TI - Transplantation of putative preneoplastic hepatocytes of analbuminemic rats in the livers of Sprague-Dawley x analbuminemic hybrid rats. AB - As the analbuminemia of analbuminemic rats (NAR) is inherited as a recessive trait, the livers of F1 hybrids of Sprague-Dawley X NAR (SD X NAR) retain the capability to produce albumin. We induced albumin-negative hyperplastic nodules in the livers of NAR, isolated the nodule cells and transplanted them in the livers of SD X NAR by infusion into the mesenteric vein. When the hosts were treated with dietary 2-acetylaminofluorene plus a partial hepatectomy, numerous albumin(-) nodules of donor origin were formed within the albumin(+) livers of the hosts. This system should be useful to analyze sequential events during hepatocarcinogenesis by using a genotypic marker. PMID- 3104253 TI - The collaboration of H-2 identical bone marrow cells in in vivo antitumor activity of immune mouse splenocytes. AB - Antitumor activity of Meth A-immune BALB/c mouse spleen cells (Meth A-Im-SPL) was assayed by a Winn test in CD-1(nu/nu) or BALB/c(nu/nu) chimeric mice which were reconstituted with the bone marrow cells of various strains of mice. It was found that Meth A-Im-SPL (L3T4+ T cells) neutralized the tumor in collaboration with H 2 compatible bone marrow or bone marrow-derived cells. PMID- 3104254 TI - Organ-specific effects of 1,2-dimethylhydrazine in hamster. AB - Uptake and metabolism of the carcinogen 1,2-dimethylhydrazine (DMH) were compared in isolated epithelial cells from the colon and the small intestine. A new method was developed to separate colonic epithelial cells into surface columnar cells and crypt cells without the use of any proteolytic enzymes. Colonic columnar cell enriched fraction exhibited DMH metabolism two to three times higher than that of crypt cells. The carcinogen binding was much lower in the small intestine as compared to the colon. In the small intestine, the crypt cell-enriched fraction showed higher carcinogen binding as compared to villus cells. Pyrazole was found to inhibit DMH binding by isolated small intestinal and colonic epithelial cells. The extent of inhibition was maximum in cells showing the greatest ability to incorporate DMH. PMID- 3104256 TI - Induction of hepatic tumors by diethylstilbestrol in N-nitrosobutylurea-initiated female rats. AB - The carcinogenic effect of estrogens, diethylstilbestrol (DES) and 17 beta estradiol (E2), and its modification by N-nitrosobutylurea (NBU) were studied in female W/Fu rats. Multiple mammary tumors (MT) of medullary carcinoma type developed at a high rate following prolonged treatment with estrogens. All MTs were located adjacent to the nipple and were slow-growing. The induction rate, multiplicity and size of estrogen-induced MTs were not influenced by pretreatment with a small amount of NBU, which alone did not induce any tumor. Ten of 12 rats (82%) receiving combined treatment with NBU and DES developed hepatic tumors (HT), while no rats in other treatment groups developed HT. All HTs were multiple nodules of various sizes bulging from the liver surface, and were considered to be neoplastic nodules. A high frequency of HT development was unexpected, because independent treatment with NBU or DES alone did not induce HT in female rats. It appears that DES played a role as a carcinogen, inducing MT and pituitary tumor (PT) through its estrogenic potency (like natural estrogen, E2), while it also acted as a promoter or co-carcinogen in the induction of HT through its pharmacologic effects. These findings may be relevant to an increased frequency of liver neoplasm among women taking oral contraceptives containing synthetic estrogens. PMID- 3104255 TI - Induction of intestinal metaplasia in rats by N-ethyl-N'-nitro-N-nitrosoguanidine but not by sodium hydroxide. AB - Intestinal metaplasia (IM) in the glandular stomach of male Wistar rats induced by oral administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and/or intubation of 0.1N sodium hydroxide (NaOH) was studied as follows. Experiment I, sequential study: Rats in group I were given 100 micrograms/ml ENNG in drinking water for 12 weeks. Rats in group II were given 5 ml of 0.1N NaOH by gastric intubation once a week for 12 weeks. Group III control rats were given tap water. Rats were killed from week 1 until week 69 sequentially. IM was first found at week 26 in group I and at week 58 in groups II and III, its incidence being significantly higher in group I than in the other two groups (P less than 0.01), but without any difference between group II and group III. Experiment II, two stage carcinogenesis: Rats in groups I and II were treated in the same way as in experiment I, while rats in group III were given 100 micrograms/ml ENNG for 12 weeks, followed by 0.1N NaOH once a week for 12 weeks intragastrically. All rats were killed at week 56. The numbers of metaplastic glands in groups I and III were higher than in group II. Gastric carcinomas were induced in all groups of rats treated with ENNG. The results of these two experiments show that IM is effectively induced by a carcinogen but is not enhanced by regeneration induced by alkaline treatment. PMID- 3104257 TI - The carcinogenicity of quinoline and benzoquinolines in newborn CD-1 mice. AB - The environmental occurrence and mutagenic activity of quinoline and benzoquinolines are well-documented. In this study, the relative carcinogenic activities of quinoline, benzo[f]quinoline, benzo[h]quinoline, and phenanthridine were evaluated in newborn mice. Mice were injected intraperitoneally on the first, eighth, and fifteenth day of life with 0.25, 0.5, and 1.0 mumol of each of these aza-arenes. Quinoline induced a 71% incidence (P less than 0.005) of hepatic tumors among the male mice sacrificed at 52 weeks of age. None of the female mice treated with these aza-arenes developed hepatomas. Among the female mice treated with quinoline there was a significant development of leukemia or lymphoma (P less than 0.05) which was not evident among the female mice in any of the other experimental groups. Benzo[h]quinoline and phenanthridine were not carcinogenic under these assay conditions. Benzo[f]quinoline did induce an increase in the incidence of hepatomas among male mice (19% as compared to 5.9% among controls). This increase, however, was not statistically significant. These data indicate that quinoline has greater carcinogenic potential than any of these isomeric benzoquinolines in newborn mice. PMID- 3104258 TI - Metabolic activation of phenacetin and phenetidine by several forms of cytochrome P-450 purified from liver microsomes of rats and hamsters. AB - Metabolic activation of phenacetin by liver microsomes proceeds via both phenetidine and N-hydroxyphenacetin to direct-acting mutagens, i.e., N hydroxyphenetidine and p-nitrosophenetole. Five different molecular species of cytochrome P-450 have been purified from liver microsomes of drug-pretreated Wistar rats or Syrian hamsters and their abilities to activate phenetidine and phenacetin were compared using reconstituted microsome systems. High-spin forms of cytochrome P-450 purified from 3-methylcholanthrene-pretreated rats (MC-P-448 H) or hamsters (P-488 ham-II) showed higher catalytic activity for N hydroxylation of phenetidine than three other low-spin forms of cytochrome P-450 purified from the same animals or from phenobarbital-pretreated rats. MC-P-448-H and P-488 ham-II required the presence of cytochrome b5 for their maximum activities in the reconstituted system. The five forms of cytochrome P-450, however, exhibited no measurable activity for N-hydroxylation of phenacetin either with or without cytochrome b5. The mutagenicity of phenacetin and phenetidine toward Salmonella typhimurium TA100 was generated when the reconstituted microsomes containing MC-P-488-H or P-488 ham-II were used as activating enzymes. From these results, it was suggested that high-spin forms of cytochrome P-450 (MC-P-448-H and P-448 ham-II) played an important role in the metabolic activation of phenacetin to the direct-acting mutagens. PMID- 3104259 TI - Recent trends in different histological types of lung cancer in Tokyo based on pathological autopsy records. AB - The recently increasing trend of lung cancer mortality in Japan was qualitatively analyzed. As the percentages of cases undergoing pathological autopsies in Tokyo were thirty for males and twenty-six for females during the period from 1979 to 1983, the histologically classified death rates in Tokyo could be estimated by combining the reported cases of death from lung cancer with the proportion of these of known histological type. The results indicated an increase in adenocarcinoma, and a decrease in squamous-cell carcinoma, except for the older age-group of men. The latter result suggested that the results were affected by the decreasing proportion of smokers and by the improvement in cigarette quality. The increase in small-cell and large-cell carcinoma, and the decrease in undifferentiated carcinomas, could be explained by problems associated with differing diagnostic standards. However, when these three different types of carcinoma were considered as a single type, the death rate was shown to be increased except in younger age-groups of women. PMID- 3104260 TI - Heterogeneity of acute undifferentiated leukemia at the immunoglobulin and T-cell receptor genes level. AB - Phenotypic markers of leukemic cells from 76 children with acute leukemia were examined. Of these cases, 7 were diagnosed as acute undifferentiated leukemia (AUL) whose leukemic cells were negative for myeloperoxidase and did not react with lineage-specific or lineage-associated monoclonal antibodies. Then, we analyzed the configuration of both immunoglobulin (Ig) and T-cell receptor beta chain (T beta) gene in these 7 AUL cases. Three cases had no rearrangement of Ig or T beta genes which was suggestive of non-lymphoid origin of these cases. In contrast, 4 cases showed rearrangements of Ig and/or T beta genes. One of these 4 cases demonstrated T beta gene rearrangement with retention of the germline configuration of Ig genes. Two cases with both Ig and T beta gene rearrangements also showed kappa-chain gene rearrangements. These findings indicate the heterogeneity of AUL at the DNA level, and may cast new light on the early differentiation of hematopoietic progenitor cells. PMID- 3104261 TI - Synergistic antitumor effects of BCG and monoclonal antibodies capable of inducing antibody-dependent cell-mediated cytotoxicity. AB - Three monoclonal antibodies (MAbs) of different immunoglobulin subclasses against MH134 murine ascitic hepatoma cells, detecting the same antigenic determinant of tumor-associated antigen of the tumor cells, were tested for their ability to produce a synergistic antitumor effect with Mycobacterium bovis BCG in C3H/HeN mice. 12A2 (IgG2a) induced both antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against the tumor cells. C3H/HeN mice were inoculated ip with MH134 tumor cells (day 0), and received an ip injection of BCG (day 1) and/or 12A2 (day 5). The combined therapy with BCG and 12A2 brought about a significant prolongation of the survival period, whereas either BCG or the MAb alone exhibited poor therapeutic effectiveness. 11G2 (IgG1), inducing ADCC but not CDC against MH134 tumor cells, was shown to exhibit antitumor effects as potent as those of 12A2, when used in combination with BCG. However, 7C2 (IgM), capable of inducing CDC but not ADCC to the tumor cells, produced no apparent synergistic effect with BCG. ADCC of BCG-induced peritoneal cells was mediated by the adherent cell population of the cells and abolished by the addition of carrageenan, suggesting that the effector cells of the cytotoxicity were macrophages. Moreover, carrageenan abolished the combined antitumor effect of BCG and these MAbs in the serological Winn assay. These results suggest that activated macrophages play a major role in the synergistic antitumor effect of BCG and MAbs capable of inducing ADCC against MH134 tumor. PMID- 3104262 TI - Pharmaceutical aspects. Nasal and depot formulations of leuprolide. PMID- 3104263 TI - Phase III studies in prostatic cancer with leuprolide acetate. PMID- 3104264 TI - Pituitary-gonadal function in adult male rats subjected to chronic water restriction. AB - The effect of water restriction on the pituitary-gonadal axis has been studied in adult male rats. Water restriction did not modify FSH, LH and testosterone levels. However, both LH and testosterone responses to acute noise stress were impaired by water restriction. It was unlikely that the inhibition of the pituitary-gonadal response to stress was due to an alteration of the circadian pattern of LH since no evidence for such a daily rhythm was found in either of the two experimental groups. The effects of water restriction on the pituitary gonadal axis appear to be at least partially a consequence of the resulting reduction in food intake, so that the pituitary-gonadal response to stress would be a more sensitive index of abnormalities induced by protein-calorie deficit than basal concentrations of LH, FSH, or T. PMID- 3104265 TI - Hypogonadotropic hypogonadism and anosmia (Kallmann's syndrome) associated with a marker chromosome. AB - A patient with hypogonadotropic hypogonadism and anosmia (Kallmann's syndrome) had an associated chromosomal abnormality. Evaluation of the hypothalamic pituitary axis showed undetectable basal LH and FSH and slight increases in both gonadotropins in response to GnRH. Augmented gonadotropin response to GnRH after serial subcutaneous injections of GnRH confirmed a hypothalamic defect. Additional endocrine tests failed to reveal other hormone dysfunctions. A supernumerary chromosome was detected by routine chromosome analysis. The extra genetic material was identified by differential cytogenetic banding procedures as an accessory bisatellited marker chromosome originating from either chromosome group D or G. Chromosome analyses of both parents were normal. Our results suggest that, in at least some cases, the Kallmann's phenotype may be associated with a chromosome abnormality. PMID- 3104266 TI - Galactostatin, a new beta-galactosidase inhibitor from Streptomyces lydicus. PMID- 3104267 TI - Azinomycins A and B, new antitumor antibiotics. III. Antitumor activity. AB - Azinomycins A and B, isolated from the culture broth of Streptomyces griseofuscus S 42227, were examined for antitumor activities against P388 leukemia, P815 mastocytoma, B-16 melanoma, Ehrlich carcinoma, Lewis lung carcinoma and Meth A fibrosarcoma. Azinomycin B was markedly effective against the intraperitoneally inoculated tumors such as P388 leukemia, B-16 melanoma and Ehrlich carcinoma. The intraperitoneal administration of azinomycin B showed 57% survivors for 45 days and 193% ILS against P388 leukemia. For Ehrlich carcinoma, azinomycin B gave 161% ILS and 63% survivors for 45 days, but solid tumors such as Lewis lung carcinoma and Meth A fibrosarcoma were not susceptible to repeated injection of this substance. Azinomycin A was somewhat less effective than azinomycin B for the tumor systems tested. PMID- 3104268 TI - The sorangicins, novel and powerful inhibitors of eubacterial RNA polymerase isolated from myxobacteria. AB - A new antibiotic, sorangicin, was isolated from the culture supernatant of the myxobacterium, Sorangium (Polyangium) cellulosum strain So cel2. It is a macrocyclic lactone carbonic acid and is produced in two structural variants, sorangicins A and B. In addition small quantities of the respective glycosides, sorangiosids A and B, may be found. The antibiotic acts mainly against Gram positive bacteria, including myocobacteria, with MIC values between 0.01 and 0.1 microgram/ml, but at higher concentrations (MIC 3 approximately 30 micrograms/ml) Gram-negatives are also inhibited. Yeasts and molds are completely resistant. The new antibiotic is a specific inhibitor of eubacterial RNA polymerase which it blocks, however, only if added before RNA polymerization has started. PMID- 3104269 TI - Uptake of horseradish peroxidase from perilymph by cochlear hair cells. AB - The specific mechanisms involved in the uptake of an exogenous protein, horseradish peroxidase (HRP), by cochlear hair cells were studied morphologically in light and electron microscopy. HRP was internalized by coated vesicles which formed from the plasma membrane only in the basal portion of the hair cells. Inner hair cells demonstrated relatively greater uptake than adjacent outer hair cells. The lateral plasma membrane of outer hair cells was unique in that reaction product was never bound to this portion of the membrane. Subsequent to endocytosis, HRP was transported to the Golgi and its associated system of endoplasmic reticulum and lysosomes. The exogenous protein was sequestered in a striking accumulation of secondary lysosomes and multivesicular bodies which were restricted to the infracuticular region of the hair cells and persisted for periods of at least 72 h after introduction of HRP. It is not clear whether the hair cells were slowly degrading the HRP or if the lysosomal enzymes necessary for its breakdown were lacking. The pathway demonstrated by HRP uptake and intracellular transport may represent one route by which macromolecules requisite for basic metabolic or nutritional requirements of the hair cells are supplied from the perilymph. PMID- 3104270 TI - Hypoglycemia alters pulsatile luteinizing hormone secretion in the postpartum beef cow. AB - This study tested the hypothesis that the increased glucose requirement of lactation had effects that were independent of the suckling-dependent inhibition of postpartum endocrine function in beef cows. Mature Hereford cows were either suckled ad libitum and infused with saline iv (n = 9) from d 2 through 4 (d 0 = jugular catherization on d 32 +/- 3 postpartum); were nonsuckled and infused with saline from d 2 through 4 (n = 10); or were nonsuckled and infused with phlorizin (3 g/d) from d 2 through 4 (n = 10). Nonsuckled cows infused with phlorizin had lower (P less than .05) plasma concentrations of glucose and amino acid nitrogen (AAN) on d 2 compared with pre-infusion levels (d 1), but their metabolic profile returned to levels similar to the suckled cows by d 3 and 4. Nonsuckled cows infused with saline had elevated glucose and insulin and lower AAN and free fatty acids (FFA) on d 3 and 4 compared with pre-weaning (d 1) levels (P less than .05). Nonsuckled cows infused with phlorizin did not show this weaning-induced elevation in glucose and insulin. The number of luteinizing hormone (LH) pulses was not affected by treatment. However, in contrast to the large LH pulses observed in the nonsuckled cows infused with saline, both the suckled cows and the nonsuckled cows treated with phlorizin had more small and fewer large amplitude pulses (P less than .01). Treatment did not affect serum concentrations of follicle stimulating hormone, gonadotropin release in response to gonadotropin releasing hormone (25 micrograms) or the number of cows ovulating by 55 d after calving. We conclude that the increased glucose clearance caused by phlorizin infusion or lactation results in depression of LH pulse amplitude in suckled postpartum beef cows. PMID- 3104271 TI - Enhancement of ovulation rate in gilts by increasing dietary energy and administering insulin during follicular growth. AB - Two experiments were conducted to examine influences of dietary energy and insulin on ovulation rate and patterns of luteinizing hormone (LH), follicle stimulating hormone (FSH), glucose, insulin and estradiol in gilts during 6 d before estrus. In Exp. 1, 36 gilts were given altrenogest for 14 d to synchronize estrus. In a factorial arrangement, gilts were fed one of two levels of dietary energy (5,771 or 9,960 kcal metabolizable energy (ME)/d), and given one of two levels of porcine insulin (0 or .1 IU/kg body weight iv every 6 h). Dietary treatments began 4 d before and insulin treatments began 1 d after the last day of altrenogest, respectively, and lasted until 24 h after estrus. Main effect means for number of corpora lutea were 14.0 +/- 1.3 and 17.6 +/- .9 for 5,771 and 9,960 kcal ME (P less than .05), and 14.6 +/- 1.0 and 17.0 +/- .9 for 0 and .1 IU insulin (P less than .05). Number of LH peaks on d 3 was greater for gilts that received 9,960 kcal than 5,771 kcal (3.3 +/- .2 vs 2.7 +/- .2; P less than .05), and for .1 than 0 IU insulin (3.2 +/- .2 vs 2.7 +/- .2; P less than .05). During the first 24 h of sampling, concentrations of LH and FSH were greater (P less than .05) in gilts receiving 9,960 kcal ME plus insulin than for other treatment combinations. Concentrations of estradiol were not affected by treatments. In Exp. 2, two formulations of insulin were evaluated for influence on ovulation rate. All gilts received altrenogest and 9,960 kcal ME/d as in Exp. 1. Then on the first day after altrenogest, seven gilts each received short-acting insulin (as in Exp. 1), long-acting insulin (zinc suspension, 1.0 IU/kg body weight every 18 to 24 h), or served as controls. Ovulation rates were increased (P less than .05) by both insulin preparations (15.6, control; 19.1, short-acting; 18.5, long acting; SE = 1.2). Concentrations of LH tended to be greater after short-acting insulin, but differences were not significant (P = .13). We conclude that increases in ovulation rate produced by dietary energy and insulin are not necessarily accompanied by changes in gonadotropins or estradiol. PMID- 3104272 TI - Mupirocin ('pseudomonic acid')--a promising new topical antimicrobial agent. PMID- 3104273 TI - Combined imipenem/cilastatin and tobramycin therapy of multiresistant Pseudomonas aeruginosa in cystic fibrosis. AB - Ten patients with cystic fibrosis (CF) and chronic broncho-pulmonary Pseudomonas aeruginosa infection were given imipenem/cilastatin (100 mg/kg/day) in combination with tobramycin (15 mg/kg/day). Forced vital capacity and forced expiratory volume in the first second improved significantly in nine out of ten patients, and most of the patients improved clinically. P. aeruginosa was not eradicated in any patient and resistance against imipenem developed in all patients during treatment. A concomitant increase in MIC of piperacillin and ceftazidime occurred during treatment. In-vitro bactericidal synergy of imipenem and tobramycin was noted in 57% of pretreatment isolates. Seven patients complained of adverse reactions, mainly gastrointestinal, and treatment of three patients was discontinued after 5, 8, and 12 days of therapy, because of rash or nausea and vomiting. The side effects were considered to be due to imipenem/cilastatin. Because of the rapid development of imipenem resistance despite combination therapy, the high proportion of side effects, and the risk of induction of beta-lactam resistance, imipenem/cilastatin cannot be recommended for routine treatment of CF-patients with P. aeruginosa infection. PMID- 3104274 TI - Chequerboard titrations: the influence of the composition of serial dilutions of antibiotics on the fractional inhibitory concentration index and fractional bactericidal concentration index. AB - Chequerboard titrations carried out with modified serial dilutions of antibiotics such that consecutive concentrations in these series were four times smaller than those in two-fold serial dilutions enable MICs and MBCs to be determined with greater accuracy. Interaction indices calculated by this method can differ markedly from those calculated on the basis of two-fold serial dilutions. The differences calculated in this study ranged from -0.30 to +1.06. PMID- 3104275 TI - Imipenem and ceftazidime resistance in Pseudomonas aeruginosa and Klebsiella pneumoniae. PMID- 3104276 TI - Beta-lactamase induction and aminoglycoside susceptibility in Pseudomonas aeruginosa. AB - Recent clinical reports have described the emergence of cross-resistance to aminoglycosides during beta-lactam therapy. We therefore studied the effect of imipenem-mediated beta-lactamase induction on the susceptibilities of 92 clinical isolates of Pseudomonas aeruginosa to gentamicin, tobramycin, and amikacin. We performed a disc approximation test to look for truncation by imipenem of the inhibitory zone sizes of the aminoglycosides. We also compared aminoglycoside inhibitory zone sizes of strains grown in the presence and absence of subinhibitory concentrations of imipenem. Finally, we compared aminoglycoside MIC values determined with and without subinhibitory concentrations of imipenem. The results showed that simultaneous emergence of resistance to beta-lactams and aminoglycosides is very rare. PMID- 3104278 TI - Transport of chloramphenicol into sensitive strains of Escherichia coli and Pseudomonas aeruginosa. AB - The uptake of chloramphenicol by susceptible strains of Escherichia coli and Pseudomonas aeruginosa was measured as the depletion of 14C-chloramphenicol from the supernatant of centrifuged cultures. Chloramphenicol did not bind to nongrowing cells or isolated cell envelopes. Chloramphenicol was recovered from cells in an unchanged form and was intracellularly concentrated several times above external concentrations. The net accumulation of the drug was reduced by an inhibitor of electron transport, by an oxidative phosphorylation uncoupler, by an inhibitor of high energy phosphate synthesis, and by lowering the temperature to +15 degrees C. The initial uptake of drug was saturated at 1.98 mM chloramphenicol in the medium. A 100-fold excess of each of the unlabelled isomers: L-threo, D-threo, and L-erythro chloramphenicol in cultures of either strain effectively reduced the uptake of 14C-chloramphenicol. These results indicate that chloramphenicol enters Gram-negative bacteria by means of an energy dependent process. PMID- 3104277 TI - In-vitro antimicrobial activity of enoxacin in combination with eight other antibiotics against Pseudomonas aeruginosa, Enterobacteriaceae and Staphylococcus aureus. AB - Susceptibilities of 28 strains of Pseudomonas aeruginosa, 32 strains of Enterobacteriaceae and 24 strains of Staphylococcus aureus were tested against combinations of enoxacin with either cefsulodin, piperacillin, or amikacin, enoxacin with either aztreonam, latamoxef or amikacin, and enoxacin with either oxacillin, clindamycin or vancomycin, respectively. Synergy was detected by the agar dilution technique and was defined as a four-fold decrease in the inhibitory concentration of both drugs (sigma FIC less than or equal to 0.5). Against Ps. aeruginosa, synergy occurred in 28.5% of the strains for enoxacin plus cefsulodin, 17.6% for enoxacin plus piperacillin, and 3.7% for enoxacin plus amikacin. Against the Enterobacteriaceae, synergy was detected with enoxacin plus aztreonam, latamoxef or amikacin in 9.3%, 3.1% and 0% of strains, respectively. Against Staph. aureus, no synergy was demonstrable with enoxacin plus oxacillin, clindamycin or vancomycin. No antagonism was detected for any combination tested. Selected strains demonstrating synergy by the agar dilution method for enoxacin plus cefsulodin or piperacillin failed to show synergy in kinetic studies. PMID- 3104279 TI - Oxamniquine pharmacokinetics in hepatosplenic schistosomiasis in the Sudan. AB - Oxamniquine pharmacokinetics were determined in five normal Sudanese subjects and nine Sudanese patients with advanced hepatosplenic schistosomiasis, given 1 g as a single oral dose. There were no significant differences in oxamniquine mean area under the plasma concentration time curve (AUC), plasma half life (T1/2), or time to reach peak concentration (Tmax). However, patients had a 19% lower mean AUC, a 36% higher T1/2, and a 23% increase in Tmax. The peak concentration (Cmax) was 36% lower in patients (P = 0.04). There was no correlation between disease severity and oxamniquine pharmacokinetic values. A significant correlation between oxamniquine AUC and T1/2 suggests that its elimination may be non-linear. The higher dosage requirements for oxamniquine in the Sudan are unlikely to be due to lower plasma concentrations amongst the Sudanese. PMID- 3104280 TI - Cardiac output in exercise by impedance cardiography during breath holding and normal breathing. AB - Estimation of cardiac output by impedance cardiography (QZ) in exercise during normal breathing (NB) has been limited by motion artifact. Our objective was to obtain readable impedance cardiograms on five subjects during upright cycle exercise at 0, 50, 100, 150, and 200 W to permit comparisons of QZ during NB, expiratory breath hold (EXP) and inspiratory breath hold (INSP). Q was also determined using an equilibration CO2 rebreathing method [Q(RB)]. QZ during NB exceeded EXP QZ at 100, 150, and 200 W, and exceeded INSP QZ at 100 W (P less than 0.05). The low EXP QZ values were due to a significantly lower stroke volume at 100, 150, and 200 W (P less than 0.05). For the INSP QZ at 100 W, heart rate was lower than during EXP (P less than 0.05). Regression of QZ (NB) against Q(RB) resulted in a linear relationship (r = 0.93) over the range of Q = 7-26 1/min. The slope of the regression differed significantly from 1.0 (P less than 0.05). We conclude that QZ values obtained during EXP or INSP should not be assumed to represent QZ during NB, at least at work rates greater than 50 W. A consequence of the linear relationship between QZ(NB) and Q(RB) over the range of 0-200 W is that estimates of CO2 rebreathing cardiac output can be obtained by impedance cardiography if QZ is adjusted using an appropriate empirical factor. PMID- 3104281 TI - Does interstitial lung edema compress airways and arteries? A morphometric study. AB - We compared areas and diameters of small airways and arteries in three groups of anesthetized dogs: 1) control (n = 5), 2) hydrostatic edema induced by fluid overload (n = 13), and 3) increased permeability edema induced with alpha naphthylthiourea (n = 5). We measured pulmonary arterial and wedge pressures in all groups and cardiac output in the hydrostatic edema group. Postmortem, lobes were frozen at functional residual capacity and samples taken for measurements of extravascular lung water (Qwl/dQl) and for light microscopy. We also examined lobes from hydrostatic edema experiments fixed at transpulmonary pressures of 5 and 27 cmH2O. From the histology slides, bronchovascular bundles with respiratory bronchioles (n = 706) and bronchioles (n = 467) were photographed and airway and vessel areas and diameters measured. Alveolar and airway luminal edema were graded. We found that only in hydrostatic edema, pulmonary arterial and wedge pressures increased and vascular resistance fell with fluid infusion. Mean Qwl/dQl values were 3.80 +/- 0.17, 6.81 +/- 0.96, and 9.34 +/- 0.62 (SE) in control, hydrostatic, and increased permeability edema groups, respectively. By quantitative histology, airway and arterial areas and diameters did not decrease in edema and rose with increasing transpulmonary pressure. Variable quantities of air-space edema were seen. We conclude that interstitial edema does not compress small airways or arteries and that other mechanisms, including alveolar and airway luminal edema, may explain reported increases in airway resistance. PMID- 3104282 TI - Lipoxygenase and cyclooxygenase blockade by BW 755C enhances pulmonary hypoxic vasoconstriction. AB - Lipoxygenase products (leukotrienes) have been proposed as the mediators of pulmonary hypoxic vasoconstriction. However, the supporting data are inconclusive because the lipoxygenase and leukotriene receptor blockers that reduce hypoxic vasoconstriction (such as diethylcarbamazine and the FPL's) have confounding effects. We investigated BW 755C, a potent inhibitor of both lipoxygenase and cyclooxygenase, in eight intact anesthetized dogs with acute left lower lobe atelectasis. We examined two manifestations of hypoxic vasoconstriction: shunt fraction, as an inverse indicator of regional constriction in response to local hypoxia, and the pulmonary pressor response to global alveolar hypoxia, as an index of general hypoxic vasoconstriction. During normoxia, shunt fraction, measured using a sulfur hexafluoride infusion, was 32.0 +/- 7.0%. The pulmonary pressor response to hypoxia, defined as the increase in pulmonary end-diastolic gradient produced by 10% O2 inhalation, averaged 4.5 +/- 1.8 mmHg. Then, during normoxia, BW 755C was administered. Shunt fraction fell in all eight dogs from the previous mean of 32% to 25.5 +/- 6.1% (t = 6.5, P less than 0.0005). The hypoxic pressor response rose in all dogs, from the previous 4.5 mmHg to 9.0 +/- 3.5 mmHg (t = 4.5, P less than 0.005). BW 755C enhances hypoxic vasoconstriction, an effect consistent with its activity as a cyclooxygenase inhibitor. These data do not support a substantive role for the lipoxygenase pathway in hypoxic vasoconstriction. PMID- 3104283 TI - Effect of inspiratory resistive loading on control of ventilation during progressive exercise. AB - Eight healthy volunteers performed gradational tests to exhaustion on a mechanically braked cycle ergometer, with and without the addition of an inspiratory resistive load. Mean slopes for linear ventilatory responses during loaded and unloaded exercise [change in minute ventilation per change in CO2 output (delta VE/delta VCO2)] measured below the anaerobic threshold were 24.1 +/ 1.3 (SE) = l/l of CO2 and 26.2 +/- 1.0 l/l of CO2, respectively (P greater than 0.10). During loaded exercise, decrements in VE, tidal volume, respiratory frequency, arterial O2 saturation, and increases in end-tidal CO2 tension were observed only when work loads exceeded 65% of the unloaded maximum. There was a significant correlation between the resting ventilatory response to hypercapnia delta VE/delta PCO2 and the ventilatory response to VCO2 during exercise (delta VE/delta VCO2; r = 0.88; P less than 0.05). The maximal inspiratory pressure generated during loading correlated with CO2 sensitivity at rest (r = 0.91; P less than 0.05) and with exercise ventilation (delta VE/delta VCO2; r = 0.83; P less than 0.05). Although resistive loading did not alter O2 uptake (VO2) or heart rate (HR) as a function of work load, maximal VO2, HR, and exercise tolerance were decreased to 90% of control values. We conclude that a modest inspiratory resistive load reduces maximum exercise capacity and that CO2 responsiveness may play a role in the control of breathing during exercise when airway resistance is artificially increased. PMID- 3104284 TI - Ventilatory and blood gas dynamics at onset and offset of exercise in the pony. AB - The purpose of these experiments was to examine the temporal pattern of arterial carbon dioxide tension (PaCO2) to assess the relationship between alveolar ventilation (VA) and CO2 return to the lung at the onset and offset of submaximal treadmill exercise. Five healthy ponies exercised for 8 min at two work rates: 50 m/min 6% grade and 70 m/min 12% grade. PaCO2 decreased (P less than 0.05) below resting values within 1 min after commencement of exercise at both work rates and reached a nadir at 90 s. PaCO2 decreased maximally by 2.5 and 3.5 Torr at the low and moderate rate, respectively. After the nadir, PaCO2 increased across time during both work rates and reached values that were not significantly different (P greater than 0.05) from rest at minute 4 of exercise. Partial pressure of O2 in arterial blood and arterial pH reflected hyperventilation during the first 3 min of exercise. At the termination of exercise PaCO2 increased (1.5 Torr) above rest (P less than 0.05), reaching a zenith at 2-3 min of recovery. These data suggest that VA and CO2 flow to the lung are not tightly matched at the onset and offset of exercise in the pony and thus challenges the traditional concept of blood gas homeostasis during muscular exercise. PMID- 3104285 TI - Increased HVR in pregnancy: relationship to hormonal and metabolic changes. AB - In prior studies at high altitude, we have found that pregnancy increases maternal hypoxic ventilatory response (HVR) but the factors responsible are unknown. Changes in metabolic rate and hormones that occur during pregnancy have previously been shown to influence HVR. We therefore sought to determine the contribution of metabolic rate and hormonal changes to the pregnancy-associated rise in HVR. Pregnancy increased HVR in each of 20 normal, low-altitude (1,600 m) residents. As measured by the shape parameter A, HVR at week 36 was 237 +/- 26 (SE) or twofold higher than the 124 +/- 13 value measured 3 mo postpartum (P less than 0.01) despite the presence of the potentially depressant effects of hypocapnia [change in alveolar partial pressure of CO2 (delta PACO2) = -4 +/- 1 mmHg] and alkalosis [change in arterial pH (delta pHa) = 0.02 +/- 0.01 U] during pregnancy. Sixty percent of the increase in HVR values had occurred by week 20 of gestation at which time O2 consumption (VO2) and CO2 production (VCO2) were unchanged relative to values measured postpartum. The remaining 40% rise in HVR paralleled increases in VO2 and VCO2, and further elevation in VO2 and VCO2 with moderate exercise produced an additional increase in HVR. Serum estradiol and progesterone levels increased with pregnancy, but levels did not correlate with HVR. The women reporting the greatest symptoms of dyspnea had higher HVR A values at week 36 than the least dyspneic women (285 +/- 28 vs. 178 +/- 34, respectively, P less than 0.05). We concluded that factors intrinsic to pregnancy in combination with increased metabolic rate raised HVR twofold with pregnancy and may have contributed to the often-reported symptoms of dyspnea in pregnant women. PMID- 3104286 TI - Cyclooxygenase metabolites are compartmentalized in the human lower respiratory tract. AB - Cyclooxygenase metabolites of arachidonic acid are thought to play an important role in the regulation of diverse physiological functions in the lung. Although the concentration of these metabolites required to have effects is several orders of magnitude greater than the concentration of these mediators in the blood, it has been postulated that local concentrations within tissues are much higher. In a direct test of this hypothesis, the concentrations of the cyclooxygenase products of arachidonic acid including prostaglandin (PG) E, PGF2 alpha, 6-keto PGF1 alpha, and thromboxane B2, were measured in a specialized tissue compartment, the epithelial surface of the lower respiratory tract. The concentration of these mediators within this compartment was 50- to 80-fold greater than concurrent blood levels and are sufficient to likely have physiological effects. Thus the epithelial surface of the lower respiratory tract represents a specialized compartment with high local levels of cyclooxygenase products of arachidonic acid. PMID- 3104287 TI - Blood flow in respiratory muscles during maximal exertion in ponies with laryngeal hemiplegia. AB - Laryngeal hemiplegia increases the respiratory effort required during exercise. By use of 15-micron-diam radionuclide-labeled microspheres, respiratory muscle blood flows were studied at rest, submaximal exercise (SE), maximal exercise (ME), and ME + adenosine (3 mumol X kg-1 X min-1) in nine healthy laryngeal hemiplegic (LH) ponies to ascertain whether vasodilator reserve in these tissues may be exhausted during SE, which caused maximal respiratory frequency (f) to be reached. Blood flows were also studied in the limb muscles, and data were compared with normal ponies (M. Manohar, J. Appl. Physiol. 60: 1571-1577, 1986). The heart rate, f, and change in pleural pressure in LH ponies during SE were 205 +/- 5 beats/min, 91 +/- 10 breaths/min, and 61.2 +/- 8.7 cmH2O. Corresponding values for ME were 223 +/- 2 beats/min, 90 +/- 7 breaths/min, and 75.1 +/- 5.2 cmH2O. The treadmill speed for SE was set at 75% of that for ME. Mean aortic pressure (161 +/- 9 mmHg), diaphragmatic (206 +/- 27 ml X min-1 X 100 g-1), and intercostal muscle (124 +/- 12 ml X min-1 X 100 g-1) blood flows in LH ponies increased markedly with SE and these values were not different from ME (170 +/- 5 mmHg, 293 +/- 40 ml X min-1 X 100 g-1, 167 +/- 15 ml X min-1 X 100 g-1, respectively). This suggested that maximal vasodilation in the respiratory muscles was achieved during SE. Vascular resistance in the diaphragm and intercostal muscles of LH ponies also remained similar for SE, ME, and ME + adenosine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104288 TI - Effects of pulse-modulated microwave radiation and conventional heating on sperm production. AB - The effects on testicular function of pulse-modulated microwave radiation (PM MWR, 1.3 GHz) and of conventional heating were studied in the rat. Anesthetized adult males (Sprague-Dawley, 400-500 g) were treated then killed at specific intervals with respect to the 13-day cycle of the seminiferous epithelium. PM MWR at 7.7 mW/g (90 min) yielded a modest decline in daily sperm production (DSP) that derived primarily from effects on primary spermatocytes. PM MWR at 4.2 mW/g was ineffective. The mean intratesticular temperature during the former reached 40 degrees C and did not exceed 38 degrees C during the latter. MWR considerably in excess of 7.7 mW/g yielded decrements in virtually all germ cell types, with primary spermatocytes again being most markedly affected. Using conventional heating, intratesticular temperatures in excess of 39 degrees C for 60 min were required for significant decrements in DSP. Levels of circulating follicle stimulating hormone and of leutinizing hormone were resistant to either treatment. We conclude that the damage threshold and the differential sensitivity of immature germ cells to PM MWR can be adequately explained by the consequent macroscopic heating. PMID- 3104289 TI - Comparison of volume changes in the upper airway and thorax. AB - To describe the mechanical cycles of the upper and lower portions of the respiratory system, we measured volume change in and out of the isolated upper airway in 13 anesthetized dogs and compared volume changes in the upper airway with tidal volume change during spontaneous respiratory efforts. During inspiration the onset and peak increase in volume into the upper airway preceded the onset and peak of inspiratory tidal volume by 84 +/- 8 and 638 +/- 47 ms, respectively. The volume cycle of the upper airway was nearly complete by the end of inspiratory airflow into the thorax. With progressive hypercapnia there was an increase in the change in both upper airway volume and tidal volume but the temporal sequence was preserved. End-expiratory tracheal occlusion increased the volume change in the isolated upper airway at any level of CO2; however, the effect was disproportionately greater at low rather than at high levels of CO2. Following hyperventilation-induced apnea, a change in volume in the upper airway and thorax occurred on the first inspiratory effort. In most animals at lower levels of CO2, the percent change in upper airway volume with inspiration was relatively less than tidal volume, but the reverse was true at higher levels of CO2. These differences represent dissimilarities in the mechanical forces occurring as the result of upper airway and chest wall muscle contraction during inspiration. PMID- 3104290 TI - Effects of bronchoconstriction on respiratory muscle activity during expiration. AB - The effect of methacholine-induced bronchoconstriction on the electrical activity of respiratory muscles during expiration was studied in 12 anesthetized spontaneously breathing dogs. Before and after aerosols of methacholine, diaphragm, parasternal intercostal, internal intercostal, and external oblique electromyograms were recorded during 100% O2 breathing and CO2 rebreathing. While breathing 100% O2, five dogs showed prolonged electrical activity of the diaphragm and parasternal intercostals in early expiration, postinspiratory inspiratory activity (PIIA). Aerosols of methacholine increased pulmonary resistance, decreased tidal volume, and elevated arterial PCO2. During bronchoconstriction, when PCO2 was varied by CO2 rebreathing, PIIA was shorter at low levels of PCO2, and external oblique and internal intercostal were higher at all levels of PCO2. Vagotomy shortened PIIA in dogs with prolonged PIIA. After vagotomy, methacholine had no effects on PIIA but continued to increase external oblique and internal intercostal activity at all levels of PCO2. These findings indicate that bronchoconstriction influences PIIA through a vagal reflex but augments expiratory activity, at least in part, by extravagal mechanisms. PMID- 3104291 TI - Inspiratory neuron activity in the ventrolateral medulla of the dog. AB - The purpose of this study was to describe the distribution and activity pattern of respiratory neurons located in the ventrolateral medulla (VLM) of the dog. Spike activity of 129 respiratory neurons was recorded in 23 ketamine anesthetized spontaneously breathing dogs. Pontamine blue dye was used to mark the location of each neuron. Most VLM neurons displaying respiratory related spike patterns were located in a column related closely to ambigual and retroambigual nuclei. Both inspiratory and expiratory neurons were present with inspiratory units being grouped more rostrally. The predominant inspiratory neuron firing pattern was "late" inspiratory, although eight "early" types were located. All expiratory firing patterns were the late expiratory variety. Each neuron burst pattern was characterized by determining burst duration (BD), spikes per burst (S/B), peak frequency (PF), time to peak frequency (TPF), rate of rise to peak frequency (PF/TPF), and mean frequency. CO2-induced minute ventilation increases were associated with decreases in BD and TPF and increases in PF, S/B, and PF/TPF. In 11 experiments the relative influences of vagotomy and tracheal occlusion on late inspiratory units were compared. Tracheal occlusion increased late inspiratory BD and S/B but did not alter PF/TPF. Vagotomy increased BD and S/B beyond those obtained by tracheal occlusion and, in some neurons, decreased the PF/TPF. We conclude that the location of respiratory units in the VLM of the dog is similar to that in other species, the discharge pattern of VLM respiratory units is similar to those in cat VLM, and vagotomy and tracheal occlusion affect discharge patterns differently. PMID- 3104292 TI - Frequency-dependent effects of hypercapnia on respiratory mechanics of cats. AB - The effect of increasing arterial partial pressure of CO2 (PaCO2) on respiratory mechanics was investigated in six anesthetized, paralyzed cats ventilated by constant-flow inflation. Respiratory mechanics were studied after end-inspiratory occlusions. Zero frequency resistance (Rmax), infinite frequency resistance (Rmin), and static elastance (Est) were calculated for the respiratory system, lung, and chest wall. Alveolar ventilation was manipulated by the addition of dead space to achieve a range of PaCO2 values of 29.3-87.3 mmHg. Cats did not become hypoxic during the experiment. Under control conditions marked frequency dependence in Rmax, Rmin, and Est of the respiratory system, lungs, and chest wall was demonstrated. The chest wall contributed 50% of the total resistance of the respiratory system. With increasing PaCO2 the only resistance observed to increase was Rmax of the lung (P less than 0.01). There were also no changes in the static elastic properties of either the lungs or the chest wall. These results suggest that hypercapnia increases resistance by changes in the lung periphery and not in the conducting airways. PMID- 3104293 TI - Sequential changes in lung metabolism, permeability, and edema after ANTU. AB - Lung injury and pulmonary edema were induced in rats after intraperitoneal injection of 10 mg/kg alpha-naphthylthiourea (ANTU). The time course of development of lung injury was assessed by the clearance of 99mTc diethylenetriamine pentaacetate (99mTcDTPA) from the lung into the blood, the pharmacokinetics of tritiated prostaglandin E2 [( 3H]PGE2) in the isolated perfused lung, and by increase in the weight ratio (wet-to-dry) of lung. Two hours after ANTU administration, the clearance of 99mTcDTPA was significantly faster than in untreated animals and implied an increase in permeability of the alveolar-capillary barrier. This change preceded the increase in wet-to-dry weight ratio of lung, which was not significant until 5 h after ANTU administration. The pharmacokinetics of [3H]PGE2 were significantly altered after ANTU and these changes persisted beyond the time when both lung weight ratio and 99mTcDTPA clearance had recovered to normal values. We conclude that both 99mTcDTPA clearance and PGE2 pharmacokinetics change in ANTU-induced lung injury but with different time courses. In the progressive phase of lung injury due to ANTU, the early change in clearance of 99mTcDTPA suggests that an increased permeation of the alveolar capillary barrier by this small molecule precedes pulmonary edema due to an increased colloid permeability of the barrier. Abnormal metabolism in the pulmonary microvasculature persists when the permeability defect and edema have recovered. PMID- 3104294 TI - Catheter position and blood gases during constant-flow ventilation. AB - We studied the effect of catheter position and flow rate on gas exchange during constant-flow ventilation (CFV) in eight anesthetized, paralyzed dogs. The distal tips of the insufflation catheters were positioned 0.5, 2.0, 3.5, and 5.0 cm from the tracheal carina. Flow rates were varied between 10 and 55 l/min and steady state arterial blood gases were measured. At a given flow rate, arterial CO2 pressure (PaCO2) decreased as CFV was administered further into the lung up to a distance of 3.5 cm from the carina; there were no significant differences in PaCO2 at 3.5 and 5.0 cm. For a given catheter position, PaCO2 decreased with increasing flow rate up to a flow rate of 40 l/min. Further increases in flow rate had no significant effect on PaCO2. Arterial O2 pressure (PaO2) was relatively constant at all flow rates and catheter positions. We conclude that, up to a point, CO2 elimination can be improved by positioning the catheters further into the lung; advancing the catheters further than 3.5 cm from the carina may cause over-ventilation of specific lung regions resulting in a relative plateau in CO2 elimination and relatively constant PaO2's. Positioning the catheters further into the lung permits the use of lower flow rates, thus potentially minimizing the risk of barotrauma. PMID- 3104295 TI - Airflow-induced bronchoconstriction: role of epithelium and eicosanoid mediators. AB - We examined the role of cyclooxygenase-derived metabolites and epithelial cells in airflow-induced bronchospasm. Male dogs were anesthetized and collateral system resistance (Rcs) was measured with the wedged-bronchoscope technique. A 2 min high flow challenge with dry air in nine animals produced a mean increase in Rcs of 69 +/- 13% (SE). After treatment with indomethacin (5 mg/kg), the response was significantly attenuated; Rcs increased only 40 +/- 8%. Bronchoalveolar lavage performed 5 min after a dry air challenge yielded fluid with greater concentrations of prostaglandin D2 (PGD2) and thromboxane B2 than samples from unchallenged segments. Challenge with humidified air produced a smaller physiological response than did challenge with dry air. Lavage samples obtained after dry challenge had greater concentrations of PGD2 than samples taken after challenge with humidified air. After dry air challenge, epithelial cells in lavage fluid were increased by 454 and 515% when compared with control and humidified air challenge, respectively. Significant correlations were found between epithelial cell number and PGD2 recovered in lavage fluid after dry air challenges. We conclude that both epithelial cells and prostaglandins play an important role in peripheral lung responses to dry air. PMID- 3104296 TI - Breathing pattern in hypoxic exposures of varying duration. AB - The relative contributions of breathing frequency and tidal volume to the increase in ventilation during acute or prolonged exposure to hypoxia is uncertain. We examined the changes in breathing pattern during hypoxic exposures lasting minutes, hours, and days using data from previous studies. Increased tidal volume accounted for the increased ventilation during 7-10 and 30 min of isocapnic and poikilocapnic (no CO2 added) hypoxic exposures as well as during 7 h of poikilocapnic hypobaric hypoxia (4,800 m). Tidal volume was also a greater overall contributor than frequency to increased ventilation in sea-level residents during 3 days of isocapnic hypobaric hypoxia (4,100-4,600 m) and in Denver (1,600 m) residents during 5 days on Pikes Peak (4,300 m). In sea-level residents during 3 days of poikilocapnic hypobaric hypoxia (3,600-4,300 m) and during 7-8 days on Pikes Peak, increased frequency accounted for the rise in ventilation. Tidal volume thus contributed more than frequency to increasing ventilation during brief hypoxia, whereas the contribution of frequency was increased in prolonged hypoxia involving a 4,300-m altitude ascent and hypocapnia. PMID- 3104297 TI - Effects of naloxone on breathing movements during hypercapnia in the fetal lamb. AB - To determine whether endogenous opioids influence the fetal breathing response to CO2 we have investigated the effect of the opiate antagonist, naloxone on the incidence, rate, and amplitude of breathing movements during hypercapnia in fetal lambs in utero. In 20 experiments in six pregnant sheep (130-145 days gestation) hypercapnia was induced by giving the ewe 4-6% CO2-18% O2 in N2 to breathe for 60 min. After 30 min of hypercapnia either naloxone (13 experiments) or saline (7 experiments) was infused intravenously for the remaining 30 min. During hypercapnia breath amplitude increased from 5.8 +/- 0.5 to 9.1 +/- 1.2 mmHg (P less than 0.001), and infusion of naloxone was associated with a further significant increase to 15.7 +/- 1.2 mmHg (P less than 0.001). Naloxone had no effect on the incidence or rate of breathing movements during hypercapnia. After hypercapnia there was a significant decrease in the incidence of fetal breathing movements in the naloxone group (14.7 +/- 3.2%). Infusion of saline during hypercapnia had no effect on incidence, rate, or amplitude of fetal breathing movements. These results suggest that endogenous opioids act to suppress or limit breath amplitude during hypercapnia but do not affect rate or incidence of breathing movements. PMID- 3104298 TI - Diaphragmatic function during hypercapnia: neonatal and developmental aspects. AB - The effect of acute hypercapnia on diaphragmatic force output was studied in 6 young (4-8 days) and 6 older (16-20 days) anesthetized, spontaneously breathing piglets. Diaphragmatic force output was assessed by analysis of the transdiaphragmatic pressure (Pdi) generated during phrenic nerve stimulation. Pdi was measured under base-line conditions (50% O2-50% N2) and after 10 min of hypercapnia induced by breathing 5, 10, or 15% CO2 balanced with N2 and 50% O2. Pdi was significantly less than base line during the 10 and 15% hypercapnic conditions in the young (P less than 0.05) but not the older piglets. End expiratory lung volume was noted to decrease during 15% CO2 hypercapnia. Force output augmentation occurred at this lower end-expiratory lung volume and was significantly greater in the older piglet compared with its younger counterpart (P less than 0.05). When the effects of lung volume on Pdi were corrected for, there was no age-related difference in the response to 15% CO2 hypercapnia. We conclude that severe hypercapnia has a depressant effect on diaphragmatic force output in both young and older piglets, and a differential augmentation in diaphragmatic force-output gain occurs at lower end-expiratory lung volume between young and older piglets, with the greater output occurring in the more mature animal. PMID- 3104299 TI - Neither anticoagulant nor nonanticoagulant heparin affects monocrotaline lung injury. AB - The administration of monocrotaline to rats causes pulmonary vascular leak within 1 wk followed in 2-3 wk by perivascular proliferation and fatal pulmonary hypertension. Possibly blocking the proliferation might block the pulmonary hypertension, providing insight into its mechanism. Because heparin, given as an antiproliferative agent, reduced hypoxic pulmonary hypertension in mice, it might also block monocrotaline-induced pulmonary hypertension. Alternatively, anticoagulation could worsen the lung injury. We found that heparin (300 and 600 U/kg sc twice daily) inhibited clotting in rats given monocrotaline but did not change the vascular leak, the right ventricular pressure, the right ventricular hypertrophy, the increased medial thickness of the pulmonary arterioles, or the production of a slow-reacting substance of anaphylaxis-like material by the lungs. A nonanticoagulant heparin fragment (2 mg/kg sc twice daily), given to avoid anticoagulation also did not influence the monocrotaline injury. Thus neither anticoagulant nor nonanticoagulant heparin either attenuated or worsened the measured effects of monocrotaline. PMID- 3104300 TI - Respiratory phase detection and delay determination for breath-by-breath analysis. AB - The delay between air flow and gas concentration signals is generally assumed to be constant within a breath as well as from breath to breath, but it was not possible to examine the constancy of the delay with the delay determination techniques so far available. Thus we developed new methods for respiratory phase detection and delay determination. The presented algorithm for the detection of the start of inspiration and expiration (phase detection) replaces the generally used valve assembly with two pneumotachographs. Now, the pneumotachograph is used in a bidirectional mode, but with a volume criterion for phase detection replacing the less reliable threshold criterion. To measure the delay between flow and gas concentration signals, a test gas is periodically injected as a marker. This test gas contains less N2 than ambient air. Therefore, the delay is determined as time between the moment of injection and the drop of N2. These two methods rendered it possible to examine delay variations and their consequences. The investigation of various breathing patterns demonstrated that the usually assumed errors caused by delay uncertainty are underestimated. We suggest reliance on a breath-by-breath delay determination to account for delay variations. PMID- 3104301 TI - Hypocapnia on ventral medullary blood flow and pH during hypoxia. PMID- 3104302 TI - Confirmation of a retrovirus in a B95-8 cell line. PMID- 3104303 TI - Acid hydrolysis of proteins for chromatographic analysis of amino acids. AB - The conditions used to hydrolyze proteins are vital in determining amino acid compositions because they necessarily represent a compromise aimed at yielding the best estimate of amino acid composition. Variations in ease of peptide bond cleavage, differences in amino acid stabilities, and matrix effects from nonproteinaceous components all militate against a single set of hydrolysis conditions that quantitatively hydrolyze every peptide bond and concurrently cause no destruction of any amino acid. This presentation summarizes and reviews an extensive study which evaluated a number of variations in the techniques and procedures of the classical 6N HCl, 110 degrees C, 24 h hydrolysis of protein. The objectives of the recent investigation were: to compare hydrolysis at 145 degrees C, 4 h with 110 degrees C, 24 h for proteins in a wide range of different sample matrixes; to compare protein hydrolysis at 110 degrees C, 24 h conducted in sealed glass ampoules after vacuum removal of air with hydrolysis in glass tubes with Teflon-lined screw caps after removal of air by vacuum, nitrogen purge, and sonication; to evaluate a performic acid oxidation procedure before hydrolysis for the analysis of cystine and methionine in the different sample matrixes; to evaluate multiple hydrolysis times at 145 degrees C; to evaluate the variation of interlaboratory hydrolysates prepared at 145 degrees C, 4 h in 2 different laboratories on the amino acid analysis of an array of protein containing matrixes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104304 TI - Quantitative analysis of cystine, methionine, lysine, and nine other amino acids by a single oxidation--4 hour hydrolysis method. AB - The sulfur-containing amino acids cystine and methionine play important roles in animal, especially avian, nutrition. Because these sulfur-containing amino acids are destroyed to varying extents by 6N HCl hydrolysis, oxidation and hydrolysis of cystine to cysteic acid and methionine to methionine sulfone have been widely used for determination of cystine and methionine. Lysine is considered the next limiting amino acid after the sulfur amino acids in poultry nutrition; therefore, determination of the amino acid content of rations focuses first on these 3 amino acids. The objective of this investigation was to establish whether lysine and other amino acids could be accurately determined in proteinaceous materials which had undergone performic acid oxidation. To perform this evaluation, lysine was determined in a variety of protein-containing materials both with and without performic acid oxidation. Performic acid oxidation followed by 6N HCl hydrolysis at 145 degrees C for 4 h allows accurate measurement of 3 amino acids especially important to poultry nutrition, cystine, methionine, and lysine, in a single preoxidized hydrolysate; this method can be extended to another 9 protein amino acids. PMID- 3104305 TI - Liquid chromatographic determination of penicillin V potassium in tablets and powders for oral solution. AB - A reverse-phase liquid chromatographic method is described for the assay of penicillin V potassium in tablets and powders for oral solution. Under isocratic conditions, the combined use of an octadecylsilane column, with a mobile phase composed of acetonitrile-methanol-0.01M monobasic potassium phosphate (21 + 4 + 75, v/v), and photometric detection at 225 nm, separated penicillin V potassium from excipients, related compounds, and degradation products. Sulfadimethoxine was used as an internal standard. Detector responses were linearly related to concentrations of penicillin V over the range 25-225 micrograms/mL (r = 0.99997). Standard addition recoveries ranged from 98.8 to 99.9% (mean 99.5%, n = 8) for tablets and from 97.9 to 101.6% (mean 99.8%, n = 8) for powders for oral solution. The liquid chromatographic assay results were compared with those obtained by the official iodometric titration method. The proposed method is simple, selective, stability-indicating, and free from interference by excipients and degradation products. PMID- 3104306 TI - Serum immunoglobulins in psoriasis. PMID- 3104307 TI - Lithium and leukaemia--causal or coincidental? PMID- 3104308 TI - Phenytoin encephalopathy. PMID- 3104309 TI - Superoxide dismutase from the extremely halophilic archaebacterium Halobacterium cutirubrum. AB - Halobacterium cutirubrum, a member of the archaebacteria, contains one superoxide dismutase (EC 1.15.1.1). This enzyme functions in the high-ionic-strength intracellular environment and protects the organism against the toxic effects of the superoxide anion. The enzyme has been purified to about 90% homogeneity by a four-step procedure which never removes it from conditions of high ionic strength. The subunits of the purified enzyme have a molecular weight of 25,000 and are possibly in tetrameric association. The enzyme shows anomalously high resistance to azide inhibition and sensitivity to inactivation by hydrogen peroxide. Metal analysis indicates 0.2 atom of Mn, less than 0.03 atom of Cu, and less than 0.001 atom of Fe per subunit. The low content of Mn may explain the low specific activity found for this enzyme compared with that of eubacterial enzymes. Optimum activity occurs in 2 M KCl; KCl gives about twice as much activity as NaCl over the range of 2 to 4 M. The enzyme appears to be related to those isolated from other archaebacteria but also exhibits several novel features. PMID- 3104310 TI - Purification and characterization of ribitol-5-phosphate and xylitol-5-phosphate dehydrogenases from strains of Lactobacillus casei. AB - A simple three-step procedure is described which yields electrophoretically homogeneous preparations of ribitol-5-phosphate dehydrogenase and xylitol-5 phosphate dehydrogenase. The former enzyme is a 115,000-molecular-weight protein composed of two subunits of identical size and is specific for its substrate, ribitol. The xylitol-5-phosphate dehydrogenase exists as a tetrameric protein with a molecular weight of 180,000; this enzyme oxidizes the phosphate esters of both xylitol and D-arabitol. Characterization of the physical, kinetic, and immunological properties of the two enzymes suggests that the functionally similar enzymes may not be structurally related. PMID- 3104311 TI - Cyst production and brown pigment formation in aging cultures of Azospirillum brasilense ATCC 29145. AB - Encystation in Azospirillum brasilense ATCC 29145 was observed by using routine laboratory staining and phase-contrast and electron microscopy. Encystment occurred in liquid and in solid or semisolid media containing fructose (8 mM) and KNO3 (0.5 mM). The encysted forms consisted of a central body filled with poly beta-hydroxybutyric acid granules, an electron-transparent intinelike region, and a thick outer layer. Enlarged giant encysted forms with multiple central bodies were also observed during the germination of a desiccated brown colony. Morphogenetically different forms in an aging culture could be resolved by sucrose density gradient centrifugation. The dense encysted forms along with numerous granules in a fibrillar network pelleted at 70% sucrose, while empty saclike envelopes along with vegetative cells and coccoid bodies pelleted at 55% sucrose. Different media induced various degrees of pigmentation in A. brasilense ATCC 29145 after aging. The pigment possessed several of the properties reported for microbial melanins, including insolubility in water and organic solvents, solubility in cold and hot alkali, and bleaching in hydrogen peroxide. The UV absorption maxima of the alkali extract were at 280 and 310 nm. Electron micrographs of the brown pigment showed that it occurred as aggregated granules surrounding the encysting cells as well as being excreted into the medium in an aging culture. It is concluded that A. brasilense ATCC 29145 produces compounds that form a brown pigment similar to melanin and are expressed under the influence of certain cultural conditions conducive for encystment. PMID- 3104312 TI - Assembly of D-alanyl-lipoteichoic acid in Lactobacillus casei: mutants deficient in the D-alanyl ester content of this amphiphile. AB - D-Alanyl-lipoteichoic acid (D-alanyl-LTA) from Lactobacillus casei ATCC 7469 contains a poly(glycerophosphate) moiety that is acylated with D-alanyl ester residues. The physiological function of these residues is not well understood. Five mutant strains of this organism that are deficient in the esters of this amphiphile were isolated and characterized. When compared with the parent, strains AN-1 and AN-4 incorporated less than 10% of D-[14C]alanine into LTA, whereas AN-2, AN-3, and AN-5 incorporated 50%. The synthesis of D-[14C]alanyl lipophilic LTA was virtually absent in the first group and was approximately 30% in the second group. The mutant strains synthesized and selected the glycolipid anchor for LTA assembly. In addition, all of the strains synthesized the poly(glycerophosphate) moiety of LTA to the same extent as did the parent or to a greater extent. It was concluded that the membranes from the mutant strains AN-1 and AN-4 are defective for D-alanylation of LTA even though acceptor LTA is present. Mutant strains AN-2 and AN-3 appear to be partially deficient in the amount of the D-alanine-activating enzyme. Aberrant morphology and defective cell separation appear to result from this deficiency in D-alanyl ester content. PMID- 3104313 TI - 2',3'-Dialdehyde of ATP: a specific, irreversible inhibitor of component A3 of the methylreductase system of Methanobacterium thermoautotrophicum. AB - Among 17 purine and ATP derivatives tested, 3 were found to totally inhibit the methyl coenzyme M methylreductase system of Methanobacterium thermoautotrophicum at a concentration of 5 mM; these derivatives were 8-azido-ATP, alpha, beta-thio ADP and 2',3'-dialdehyde-ATP. 2',3'-Dialdehyde-ATP specifically and irreversibly bound to component A3 of the methylreductase system during ATP activation of the system. PMID- 3104314 TI - Isolation and structure of the sex pheromone inhibitor, iPD1, excreted by Streptococcus faecalis donor strains harboring plasmid pPD1. AB - The sex pheromone inhibitor iPD1, which is excreted by Streptococcus faecalis donor strains harboring bacteriocin plasmid pPD1 and which inhibits sex pheromone cPD1, was isolated, and its structure was determined. Its molecular weight is 828, and its amino acid sequence is H-Ala-Leu-Ile-Leu-Thr-Leu-Val-Ser-OH. PMID- 3104316 TI - Treatment of mania: a naturalistic study of electroconvulsive therapy versus lithium in 438 patients. AB - The efficacy of electroconvulsive therapy (ECT), adequate lithium therapy, inadequate lithium therapy, and neither ECT nor lithium therapy was compared by reviewing the charts of 438 patients hospitalized because of mania over a 12-year period. A significantly (p less than .05) greater percentage (78%) of patients who received ECT had "marked improvement" than did those who received either adequate or inadequate lithium treatment (62% and 56%, respectively) or neither treatment (37%). Of the patients with schizoaffective disorder, manic type, 87.5% who received ECT showed "marked improvement"; almost 70% of patients who failed to respond to adequate lithium had "marked improvement" with ECT. Unilateral and bilateral ECTs were equally effective. Psychosis was not useful in predicting treatment response. ECT was demonstrated to be an effective treatment for mania. PMID- 3104315 TI - Nucleotide sequence and expression of the beta-lactamase gene from Staphylococcus aureus plasmid pI258 in Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. AB - The structural gene for beta-lactamase in the Staphylococcus aureus plasmid pI258 was cloned into a Staphylococcus aureus-Bacillus subtilis-Escherichia coli shuttle vector, pWN101, and the nucleotide sequence of the gene was determined. pWN101 was structurally stable and the beta-lactamase gene was expressed efficiently from its native promoter and ribosome-binding site in all three hosts. PMID- 3104317 TI - Waldenstrom macroglobulinaemia treated with sequential hemibody irradiation. AB - A 40-year-old man presented with symptoms of anaemia and blurred vision. Waldenstrom macroglobulinaemia was diagnosed on the basis of plasmacytoid lymphocytes in the peripheral blood, extensive bone marrow involvement, and an IgM kappa monoclone in the plasma of 48 g/liter. Symptoms were immediately reversed by isovolaemic continuous-flow plasmapheresis coupled with red cell transfusion. Specific therapy was undertaken with sequential hemibody irradiation. At two years of follow-up the patient enjoys excellent health, has improved haematopoietic reserve in the bone marrow, and the only therapy required is intermittent plasmapheresis to control symptoms relating to rising viscosity. Thus, systemic irradiation, which is well tolerated and objectively reduces marrow tumour bulk, offers an alternative to chemotherapy in the palliative management of active macroglobulinaemia and may diminish but not prevent the need for intermittent plasmapheresis. PMID- 3104318 TI - Reactive sulfhydryl groups of alpha 39, a guanine nucleotide-binding protein from brain. Location and function. AB - The guanine nucleotide-binding proteins which mediate hormonal inhibition of adenylate cyclase as well as hormonal regulation of other membrane functions are alpha, beta, and gamma heterotrimers which are structurally homologous to each other. In brain, the predominant guanine nucleotide-binding component is a 39-kDa protein whose physiological role is as yet unknown. We have used N-ethylmaleimide to define functionally important sulfhydryl groups on alpha 39. Three cysteine residues in the molecule are reactive in unliganded alpha 39. Alkylation of two of these is reduced when guanosine 5'-(3'-O-thio)triphosphate (GTP gamma S) is bound. We have isolated and sequenced tryptic peptides containing the three reactive cysteines. The octapeptide containing the GTP gamma S-insensitive cysteine is at a position equivalent to amino acids 106-113 of the transducin alpha subunit (Lochrie, M. A., Hurley, J. B., and Simon, M. I. (1985) Science 228, 96-99). However, the equivalent peptide in transducin does not contain a cysteine residue. Alkylation of this cysteine blocks ADP-ribosylation of cysteine 351 by pertussis toxin. However, alkylation does not prevent association of alpha with the beta X gamma subunits nor does it inhibit GTPase activity. The two GTP gamma S-sensitive cysteines are at positions equivalent to cysteines 139 and 286 of the transducin alpha subunit. Alkylation of these residues inhibits GTPase activity. Neither of these GTP gamma S-sensitive cysteines are in those regions of alpha 39 which are highly homologous to the GTP-binding site of elongation factor Tu (Jurnak, F. (1985) Science 230, 32-36). However, both are present in the brain 41-kDa guanine nucleotide-binding protein and in the two transducins. The conservation of these cysteine residues suggests that they are important for the function of the subunits. PMID- 3104319 TI - Time-dependent restoration of the trigger pool of calcium after termination of angiotensin II action in adrenal glomerulosa cells. AB - In adrenal glomerulosa cells, angiotensin II causes an immediate release of calcium from an intracellular trigger pool (Kojima, I., Kojima, K., and Rasmussen, H. (1985) Am. J. Physiol. 247, E36-E43). The present study was conducted to determine how the trigger pool of calcium is restored after cessation of the agonist action. Upon termination of angiotensin II action, calcium influx rate decreased immediately while total cell calcium increased rapidly. The increase in total cell calcium is not affected by 1 microM nitrendipine, which blocks angiotensin II-stimulated calcium influx without inhibiting basal influx of calcium. In contrast, total cell calcium did not increase in medium containing 1 microM calcium, in which basal calcium influx is negligible. A rapid increase in total cell calcium after an addition of the antagonist was not accompanied by changes in cytoplasmic free calcium concentration. A second stimulation of cells with either angiotensin II or carbachol did not cause calcium release when the interval of two stimulations was shorter than 20 min. The longer the interval, the greater the magnitude of calcium release in response to the second stimulator. The maximum response was obtained when the interval was 40 min or more. When exogenous arachidonic acid, which mobilized calcium by acting directly on the inositol trisphosphate sensitive pool, was employed as a second stimulator, the magnitude of the decrease in total cell calcium was also dependent on the interval. These results suggest that, upon termination of angiotensin II action, calcium is rapidly accumulated first in an intracellular pool which is insensitive to either inositol 1,4,5-trisphosphate or arachidonic acid and that the trigger pool is restored gradually thereafter. PMID- 3104320 TI - Presence of a functional inhibitory GTP-binding regulatory component, Gi, linked to adenylate cyclase in adipocytes of ob/ob mice. AB - It has been reported recently (Begin-Heick, N. (1985) J. Biol. Chem. 260, 6187 6193) that adipocytes from the obese mouse strain (ob/ob), unlike normal mice (+/+), lack functional Gi, a GTP-regulated protein complex that mediates inhibition of adenylate cyclase. In contrast, we have found functional Gi linked to inhibition of adenylate cyclase in adipocyte membranes from both ob/ob and +/+ mice. This conclusion is based on observation of: 1) GTP-dependent inhibition of adenylate cyclase by antilipolytic agents, such as prostaglandin E2, nicotinic acid, and the adenosine receptor agonist, phenylisopropyladenosine (PIA); 2) classical biphasic GTP kinetics, with stimulation by low and inhibition by high concentrations of GTP; and 3) elimination of cyclase inhibition by antilipolytic agents upon treatment of ob/ob adipocytes with pertussis toxin. Upon treatment with pertussis toxin and [32P] NAD, purified adipocyte membranes from ob/ob mice incorporated twice as much radioactivity per unit membrane protein than those from +/+ mice in the 40,000-42,000 region. The inhibitory actions of PIA on adenylate cyclase were blocked by the adenosine receptor antagonists, theophylline and isobutylmethylxanthine. However, in contrast to other known inhibitory adenosine receptors, relatively high (100 nM) PIA concentrations were required for half-maximal inhibition of adenylate cyclases from both +/+ and ob/ob adipocytes. The adipocyte adenylate cyclase from both mouse strains were approximately equally susceptible to inhibition by nicotinic acid and prostaglandin E2. However, the ob/ob cyclase was inhibited by 47% with PIA, whereas the enzyme from the +/+ mouse was inhibited by only 27% (p less than 0.01). This greater inhibition by adenosine may contribute to abnormal fat metabolism in adipocytes from ob/ob mice. PMID- 3104321 TI - Different and synergistic actions of human tumor necrosis factor and interferon gamma in damage of liposome membranes. AB - The effects of human recombinant tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) in damage of liposome membranes were examined to elucidate the molecular mechanism of their antiproliferative actions on tumor cells. The extent of membrane damage was assayed by measuring the rate of release of the fluorescent dye calcein encapsulated in the liposomes at different pH values in the presence of TNF and/or IFN-gamma. At pH values below about 5, TNF bound to phospholipid liposomes composed of mixtures of phosphatidyl-serine and phosphatidylcholine in molar ratios of 2:1 and 1:2 and caused rapid release of calcein. In contrast, IFN-gamma induced very slow leakage of dye although it bound almost completely to the membranes, suggesting that it causes much less membrane damage than TNF. Small amounts of these two antitumor factors bound to phosphatidylcholine liposomes in the pH range of 4-7, inducing relatively slow leakage of calcein. In the presence of both TNF and IFN-gamma at pH 5, the maximal leakage rate was twice the sum of the rates with the two proteins individually, and the rate depended on the TNF/IFN-gamma ratio, indicating synergistic effects of TNF and IFN-gamma in induction of membrane damage. These different and synergistic actions on liposome membranes may account for the different antitumor properties of the two antitumor cytokines and their synergism. PMID- 3104322 TI - Structural and catalytic properties of L-alanine dehydrogenase from Bacillus cereus. AB - Alanine dehydrogenase from Bacillus cereus, a non-allosteric enzyme composed of six identical subunits, was purified to homogeneity by chromatography on blue Sepharose and Sepharose 6B-CL. Like other pyridine-linked dehydrogenases, alanine dehydrogenase is inhibited by Cibacron blue, competitively with respect to NADH and noncompetitively with respect to pyruvate. The enzyme was inactivated by 0.1 M glycine/HCl (pH 2) and reactivated by 0.1 M phosphate (pH 8) supplemented with NAD+ or NADH. The reactivation was characterized by sigmoidal kinetics indicating a complex mechanism involving rate-limiting folding and association steps. Cibacron blue interfered with renaturation, presumably by competition with NADH. Chromatography on Sepharose 6B-CL of the partially renatured alanine dehydrogenase led to the separation of several intermediates, but only the hexamer was characterized by enzymatic activity. By immobilization on Sepharose 4B, alanine dehydrogenase from B. cereus retained 66% of the specific activity of the soluble enzyme. After denaturation of immobilized alanine dehydrogenase with 7 M urea, 37% of the initial protein was still bound to Sepharose, indicating that on the average the hexamer was attached to the matrix via, at most, two subunits. The ability of the denatured, immobilized subunits to pick up subunits from solution shows their capacity to fold back to the native conformation after urea treatment. The formation of "hybrids" between subunits of enzyme from B. cereus and Bacillus subtilis demonstrates the close resemblance of the tertiary and quaternary structures of alanine dehydrogenases from these species. PMID- 3104323 TI - Signals for activation and proliferation of murine T lymphocyte clones. AB - Biochemical signals required for the growth of T cell clones were studied. Antigen-specific helper T cell clones, 6-1 and KO.6, could enter the state similar to the resting state where the cells expressed only small numbers of interleukin 2 (IL2) receptors and could not respond to IL2 without antigenic stimulation. A combination of a phorbol ester, 12-O-tetradecanoylphorbol-13 acetate (TPA), and a calcium ionophore, A23187, induced the expression of IL2 receptors on resting 6-1 cells and induced DNA synthesis in the presence of IL2. TPA alone did not induce IL2 receptors. A23187 induced the expression of the receptors to some extent but did not induce DNA synthesis even in the presence of IL2. IL2 receptors induced by A23187 alone were mostly low affinity receptors, whereas the combination of TPA and A23187 induced high affinity receptors in addition to low affinity receptors. Resting KO.6 cells produced IL2 in response to a combination of TPA and A23187, whereas either one of the agents did not induce the production of IL2. Dicaprylin, a permeable diacylglycerol and a potent activator of protein kinase C (the Ca2+/phospholipid-dependent enzyme) could replace TPA in both cases when dicaprylin was repeatedly added to the culture. These results suggest that strong and continuous activation of protein kinase C together with calcium mobilization is required for IL2 production and IL2 receptor expression. On the contrary, signals for DNA synthesis generated by binding of IL2 to IL2 receptors are different from those for IL2 production and IL2 receptor expression, as the combination of TPA and A23187 could not induce DNA synthesis without IL2. PMID- 3104324 TI - Crystallization and preliminary X-ray investigation of a recombinant form of human gamma-interferon. AB - A genetically engineered human gamma-interferon has been crystallized from solutions of ammonium sulfate. The crystals are trigonal, space group R32, with hexagonal axes of a = 114.0(1) A and c = 314.9(2) A. The crystals are moderately stable to x-rays and diffract to 2.85-A resolution. Density measurements indicate that the crystallographic asymmetric volume contains four interferon molecules. PMID- 3104325 TI - The D2-dopamine receptor of anterior pituitary is functionally associated with a pertussis toxin-sensitive guanine nucleotide binding protein. AB - Dopaminergic inhibition of prolactin release from the anterior pituitary may be mediated through both the adenylate cyclase and Ca2+ mobilization/phosphoinositide pathways. The D2-dopamine receptor of the bovine anterior pituitary has been partially purified by affinity chromatography on CMOS Sepharose (immobilized carboxymethyleneoximinospiperone). Reinsertion of these partially purified receptor preparations into phospholipid vesicles reconstituted guanine nucleotide-sensitive high affinity agonist binding, agonist-promoted GTPase and 35S-labeled guanosine 5'-O-(thiotriphosphate) [( 35S]GTP gamma S) binding activity in these preparations. Pertussis toxin treatment of the purified receptor preparation abolished agonist-stimulated GTPase and guanine nucleotide sensitive high affinity agonist binding. These observations suggest that the receptor copurifies with an endogenous, pertussis toxin-sensitive guanine nucleotide binding protein (N). [32P]ADP-ribosylation of affinity-purified D2 receptor preparations by pertussis toxin revealed the presence of a substrate of Mr 39,000-40,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Peptide maps generated using elastase of the [32P]ADP-ribosylated endogenous N protein, transducin, and Ni and No from brain revealed similarities but not identity between the endogenous pituitary N protein and brain Ni and No. Immunoblotting of the partially purified D2 receptor preparations showed an Mr 39,000-40,000 band with an Ni-specific antiserum raised against a synthetic peptide, and with RV3, an No-specific anti-serum, but not with CW6, an antiserum strongly reactive with brain Ni. Several lines of evidence indicate that endogenous pituitary N protein is functionally coupled to the D2 receptor. As measured by [35S]GTP gamma S binding, ratios of 0.2-0.6 mol N protein/mol receptor were observed. Association of N protein with the D2 receptor was increased by agonist pretreatment and decreased by guanine nucleotides. These results suggest that No and/or a form of Ni distinct from the Mr 41,000 pertussis toxin substrate (Ni) is the predominant N protein functionally coupled with the D2-dopamine receptor of anterior pituitary. PMID- 3104326 TI - Plasma cell membrane glycoprotein PC-1. Primary structure deduced from cDNA clones. AB - The PC-1 protein is a membrane glycoprotein that is selectively expressed on the surface of antibody-secreting cells. Previous work has shown that it consists of two apparently identical disulfide-bonded polypeptides, each of molecular weight approximately 120,000. We now describe the sequence of PC-1 mRNA and protein. The PC-1 protein is shown to consist of 905 amino acids and to have an uncommon transmembrane orientation. The NH2-terminal 58 residues are intracellular and the COOH-terminal 826 residues are extracellular. A cysteine-rich region of 85 amino acids lies adjacent to the extracellular surface of the membrane and appears to have arisen by exon duplication. In common with other membrane glycoproteins with this orientation, there is no obvious signal sequence other than the transmembrane segment. The PC-1 protein therefore has an overall structure and membrane orientation that resembles those of the transferrin receptor, the asialoglycoprotein receptor, and the Ia invariant chain. PMID- 3104327 TI - The hypoglycemic sulfonylureas glyburide and tolbutamide inhibit fatty acid oxidation by inhibiting carnitine palmitoyltransferase. AB - The hypoglycemic sulfonylureas glyburide and tolbutamide were found to be excellent inhibitors of the rat liver, heart, and skeletal muscle carnitine palmitoyltransferases, but glyburide was by far the most potent inhibitor. Carboxytolbutamide, a sulfonylurea that has no hypoglycemic effect, produced little or no inhibition of the enzyme from the three tissues examined. Fasting decreased the degree of inhibition of carnitine palmitoyltransferase by the sulfonylureas, and in genetically diabetic BB Wistar rats, a decrease in sensitivity was also clearly demonstrated. Initial rate kinetics of the inhibition of carnitine palmitoyltransferase indicated that glyburide inhibits noncompetitively with respect to palmitoyl-CoA while inhibition by malonyl-CoA was cooperatively competitive. Inhibition by malonyl-CoA was noncompetitive with respect to carnitine, but inhibition by glyburide was uncompetitive. These studies indicate that the hypoglycemic sulfonylureas inhibit carnitine palmitoyltransferase by a mechanism that is much different from inhibition by malonyl-CoA, but are, nevertheless, potent inhibitors of the enzyme. These results have important implications for energy metabolism in the liver and heart in relation to the use of sulfonylureas and for understanding the mechanism by which the sulfonylureas act to lower blood glucose, but there are also important implications of these results on the study of the metabolic regulation of fatty acid oxidation. PMID- 3104328 TI - Phorbol esters reduce gonadotrope responsiveness to protein kinase C activators but not to Ca2+-mobilizing secretagogues. Does protein kinase C mediate gonadotropin-releasing hormone action? AB - The demonstration that activators of the Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), such as phorbol esters and diacylglycerols, can provoke luteinizing hormone (LH) release from pituitary gonadotropes, suggests a possible role for protein kinase C in stimulus-release coupling. We now report that administration of phorbol myristate acetate (PMA) to pituitary cell cultures causes a sustained reduction in Triton X-100-extracted protein kinase C activity. Further, phorbol ester- and diacylglycerol-stimulated LH release, as well as inhibition by PMA of gonadotropin-releasing hormone (GnRH) stimulated inositol phosphate production, were reduced by pretreatment with PMA. The effects of phorbol ester pretreatment on PMA-stimulated LH release and protein kinase C activity were dose-dependent, sustained (greater than or equal to 24 h) and specific (no measurable effect with 4 alpha-phorbol didecanoate). The effect on PMA-stimulated LH release was apparently Ca2+-independent. In pituitary cell cultures with reduced protein kinase C activity, the gonadotropes have reduced responsiveness to PMA but release a similar proportion of cellular LH in response to Ca2+-mobilizing secretagogues (GnRH and A23187) as do control cells. The normal responsiveness to GnRH of cells with reduced responsiveness to protein kinase C activators calls into question the requirement for this enzyme for GnRH-stimulated LH release. PMID- 3104329 TI - Effect of thyrotropin-releasing hormone on the carbohydrate structure of secreted mouse thyrotropin. Analysis by lectin affinity chromatography. AB - Thyrotropin (TSH) is a glycoprotein hormone whose secretion from the anterior pituitary is regulated, in part, by the hypothalamic tripeptide thyrotropin releasing hormone (TRH). We have used serial lectin affinity analysis to explore whether TRH, in addition to promoting TSH secretion, alters the carbohydrate structure of secreted TSH. Hypothyroid mouse hemipituitaries were incubated in medium containing [3H] mannose, [3H]glucosamine, or [3H]fucose either with or without 10(-7) M TRH. TSH was immunoprecipitated, proteolytically digested into glycopeptides, and chromatographed on serial lectin-Sepharose columns. Under basal conditions, 37% of secreted [3H]mannose-labeled TSH glycopeptides failed to bind to concanavalin A (ConA)-Sepharose, 55% bound and eluted with 10 mM alpha methylglucoside, and 8% bound and eluted with 500 mM alpha-methylmannoside. Approximately 35% of glycopeptides not binding to ConA-Sepharose were bound by pea lectin-Sepharose, suggesting the presence of certain core fucosylated triantennary complex oligosaccharides. TRH caused a 2-fold increase in secretion of [3H]mannose-labeled TSH glycopeptides due almost exclusively to a specific increase in structures that bound to ConA-Sepharose and eluted with 10mM alpha methylglucoside, corresponding to biantennary complex or unusual hybrid species. There was no change in the distribution of intrapituitary TSH glycopeptides with TRH. Acid hydrolysis of secreted proteins showed little metabolism of the tritiated sugar precursors, except for a 20% conversion of [3H]mannose to [3H]fucose. Moreover, ConA-Sepharose chromatography of secreted [3H]glucosamine- and [3H]fucose-labeled TSH glycopeptides showed similar increases in ConA Sepharose binding with TRH as noted with [3H]mannose labeling. Subsequent lectin analysis of secreted [3H] mannose-labeled TSH glycopeptides on erythroagglutinating phytohemagglutinin-Sepharose and leukoagglutinating phytohemagglutinin-Sepharose disclosed no significant differences in TRH-treated versus control samples. These data suggest that secreted mouse TSH has greater carbohydrate heterogeneity than has been recognized previously. In addition, TRH in vitro promotes the secretion of specific TSH molecules apparently enriched in biantennary complex or unusual hybrid oligosaccharides. PMID- 3104330 TI - Hepatic lipase. Synthesis, processing, and secretion by isolated rat hepatocytes. AB - Hepatic lipase, a glycoprotein synthesized and secreted by the hepatocyte, binds to sinusoidal endothelium where it is involved in metabolism of lipoprotein phospholipid and triglyceride. To better understand the regulation of hepatic lipase, we investigated the synthesis, post-translational processing, and secretion of the enzyme by isolated rat hepatocytes. Metabolically labeled [35S]methionine hepatic lipase protein, produced by the collagenase-dispersed hepatocytes, was immunoisolated from detergent-solubilized cells and incubation medium at designated times, using a polyclonal rabbit anti-rat hepatic lipase antibody raised against hepatic lipase purified to homogeneity from rat liver post-heparin perfusates. Following polyacrylamide gel electrophoresis and fluorography, radiolabeled hepatic lipase was quantitated by densitometry. Newly synthesized hepatic lipase was rapidly secreted and accumulated in the medium as a 59,000-dalton protein in a manner consistent with a constitutive process. An intracellular 53,000-dalton precursor of the mature 59,000-dalton hepatic lipase was identified by immunoprecipitation. The 53,000-dalton form could also be generated by endoglycosidase digestion of the secreted 59,000-dalton protein. In pulse-chase experiments, the 53,000-dalton protein was converted into the 59,000 dalton form. A 47,000-dalton form of hepatic lipase was immunoisolated from cell lysates only after tunicamycin treatment and could be generated from the secreted 59,000-dalton enzyme by prolonged endoglycosidase digestion. These data show that hepatic lipase is synthesized and rapidly secreted by isolated rat hepatocytes. Further, an intracellular 47,000-dalton precursor peptide can be identified after tunicamycin treatment, which may represent the hepatic lipase polypeptide, presumably after removal of its signal sequence; a 53,000-dalton partially glycosylated peptide exists as a major precursor form in the cell; and the mature 59,000-dalton hepatic lipase is present in the hepatocyte, but it is rapidly secreted. PMID- 3104331 TI - Proteoglycans synthesized by cultured mouse osteoblasts. AB - Proteoglycan synthesis in nonmineralizing osteoblast cultures was investigated. Cultures were labeled with [35S]sulfate or [3H]serine, and proteoglycans were extracted from medium and cell layer with 4 M guanidine HCl. Labeled material was subjected to Sepharose CL-4B and DEAE-Sephacel chromatography and polyacrylamide gel electrophoresis. The size and composition of the glycosaminoglycan chains and the protein core size were determined. Two proteoglycan populations were isolated by Sepharose CL-4B chromatography: a minor excluded species with chondroitin sulfate chains of apparent Mr 25,000 and a smaller population (Kav = 0.43) accounting for 80% of the total labeled material. This small population resolved into two species by polyacrylamide gel electrophoresis. Both species contain dermatan sulfate chains of apparent Mr 40,000 and a core protein with Mr 45,000 on sodium dodecyl sulfate gels. With the exception of their glycosaminoglycan composition these species appear similar to those extracted from bone. In addition, high molecular weight hyaluronic acid and glycosaminoglycan peptides were found in cell extracts. PMID- 3104332 TI - In vitro regulation of granulosa cell differentiation. Involvement of cytoskeletal protein expression. AB - The link between the biochemical and morphological differentiation of granulosa cells was studied by investigating the organization and the expression of cytoskeletal proteins which determine cell shape and contacts. In cells treated with follicle-stimulating hormone (FSH), in a serum- and growth factor-free medium, or with other compounds which elevate cellular cAMP levels, the synthesis of the adherens junction proteins, vinculin, alpha-actinin, and actin was reduced significantly when compared to unstimulated cells (7-fold for vinculin, 5-fold for alpha-actinin, and 3-fold for actin). The in vitro translatability of the mRNAs coding for these proteins and the level of actin mRNA determined by RNA blot hybridization were generally reduced in differentiating cells. The synthesis and the organization of vimentin and tubulin was unaffected during this process, whereas the organization of actin and vinculin was dramatically affected, with FSH-treated cells displaying a diffuse pattern of actin and vinculin, with very little vinculin in adhesion plaques. Gonadotropin-releasing hormone agonist and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate which are known to antagonize the cAMP-mediated biochemical differentiation of granulosa cells by reducing cAMP levels or by activating protein kinase C and phospholipid turnover, blocked to a large extent the FSH-induced effect on the adherens junction proteins. Epidermal growth factor, which blocked the FSH-induced cAMP increase, but not the FSH-induced progesterone production, failed to block the synthesis of vinculin, alpha-actinin, and actin. Cytochalasin B could induce steroidogenesis and similar changes in the synthesis of these cytoskeletal proteins, whereas fibronectin, which causes cell spreading, blocked in part the FSH-induced effect on the expression of cytoskeletal proteins. The modulation of cytoskeletal proteins may therefore be an essential feature of programmed differentiation events leading to the final phenotype of granulosa cells. PMID- 3104334 TI - Reaction of discoidal complexes of apolipoprotein A-I and various phosphatidylcholines with lecithin cholesterol acyltransferase. Interfacial effects. AB - Complexes of phospholipids-apolipoprotein A-I-cholesterol, containing various bulk phosphatidylcholines or a matrix of the ether analog of 1-palmitoyl 2-oleoyl phosphatidylcholine including test phosphatidylcholines were used as substrates for human lecithin-cholesterol acyltransferase. The enzymatic reaction rates for both series of complexes were determined as a function of temperature, particle concentration, neutral salt concentration, and the type of anion present in solution. The kinetic results support the hypothesis that phospholipids, in discoidal complexes, modulate the reaction rates by molecular effects at the active site, but also by interfacial effects on the interaction of the enzyme with the particles. The relevant interfacial parameters are the lipid packing at the interface and the structure of apolipoprotein A-I. PMID- 3104333 TI - Evidence of protein kinase C involvement in phorbol diester-stimulated arachidonic acid release and prostaglandin synthesis. AB - Many stimulators of prostaglandin production are thought to activate the Ca2+- and phospholipid-dependent protein kinase first described by Nishizuka and his colleagues (Takai, Y., Kishimoto, A., Iwasa, Y., Kawahara, Y., Mori, T., and Nishizuka, Y. (1979) J. Biol. Chem. 254, 3692-3695. In this paper we report evidence that the activation of protein kinase C caused by 12-O tetradecanoylphorbol-13-acetate (TPA) is involved in the increased prostaglandin production induced by 12-O-tetradecanoylphorbol-13-acetate in Madin-Darby canine kidney (MDCK) cells. We have shown that TPA activates protein kinase C in MDCK cells with similar dose response curve as observed for TPA induction of arachidonic acid release in MDCK cells. Activation of protein kinase C was associated with increased phosphorylation of proteins of 40,000 and 48,000 daltons. We used two compounds (1-O-octadecyl-2-O-methyl-rac-glycero-3 phosphocholine (ET-18-OMe) and 1-(5-isoquinolinesulfonyl)piperazine) known to inhibit protein kinase C by different mechanisms to further examine if activation of protein kinase C was involved in the increased synthesis of prostaglandins in TPA-treated MDCK cells. We found that both compounds inhibited protein kinase C partially purified from MDCK cells and that ET-18-OMe inhibited the phosphorylation of proteins by protein kinase C in the intact cells. Addition of either compound during or after TPA treatment decreased both release of arachidonic acid from phospholipids and prostaglandin synthesis. Release of [3H]arachidonic acid from phosphatidylethanolamine in TPA-treated cells was blocked by ET-18-OMe or 1-(5-isoquinolinesulfonyl)piperazine addition. However, arachidonic acid release stimulated by A23187 is not blocked by Et-18-OMe. When assayed in vitro, treatment of cells with Et-18-OMe did not prevent the enhanced conversion of arachidonic acid into prostaglandins induced by pretreatment of cells with TPA. Our results suggest that the stimulation of phospholipase A2 activity by TPA occurs via activation of protein kinase C by TPA. PMID- 3104335 TI - Regulation of glycogen metabolism in primary cultures of rat hepatocytes. Restoration of acute effects of glucose in cells from diabetic rats involves protein synthesis. AB - Defective acute regulation of hepatic glycogen synthase by glucose and insulin, caused by severe insulin deficiency, can be corrected in adult rat hepatocytes in primary culture by inclusion of insulin, triiodothyronine, and cortisol in a chemically defined serum-free culture medium over a 3-day period (Miller, T. B., Jr., Garnache, A. K., Cruz, J., McPherson, R. K., and Wolleben, C. (1986) J. Biol. Chem. 261, 785-790). Using primary cultures of hepatocytes isolated from normal and diabetic rats in the same serum-free chemically defined medium, the present study addresses the effects of cycloheximide and actinomycin D on the chronic actions of insulin, triiodothyronine, and cortisol to facilitate the direct effects of glucose on the short-term activation of glycogen synthase. The short-term presence (1 h) of the protein synthesis blockers had no effect on acute activation of glycogen synthase by glucose in primary hepatocyte cultures from normal rats. Normal cells maintained in the presence of cycloheximide or actinomycin D for 2 and 3 days exhibited unimpaired responsiveness to glucose activation of synthase. The protein synthesis inhibitors were effective at blocking the restoration of glucose activation of synthase in diabetic cells in media which restored the activation in their absence. Restoration of glycogen synthase phosphatase activity by insulin, triiodothyronine, and cortisol in primary cultures of diabetic hepatocytes was also blocked by cycloheximide or actinomycin D. These data clearly demonstrate that restoration of acute glycogen synthase activation by glucose and restoration of glycogen synthase phosphatase activity in primary cultures of hepatocytes from adult diabetic rats are dependent upon the synthesis of new protein. PMID- 3104336 TI - The low density lipoprotein receptor. Identification of amino acids in cytoplasmic domain required for rapid endocytosis. AB - The 50-residue cytoplasmic domain of the low density lipoprotein receptor (amino acids 790-839) directs the receptor to coated pits, thereby facilitating rapid endocytosis of bound low density lipoprotein. To determine the structural features required for this targeting, we produced 24 mutations in the cytoplasmic domain through use of oligonucleotide-directed mutagenesis. The first 22 amino acids of the cytoplasmic domain (residues 790-811) are sufficient for rapid internalization. The amino acid at position 807 is especially critical. Aromatic residues (tyrosine, phenylalanine, or tryptophan) at this position allow rapid internalization. Charged or uncharged aliphatic residues do not substitute. Although the requirements at the neighboring positions (806 and 808) are less stringent, the insertion of proline at position 806 is detrimental. These specificities suggest that the juxtamembranous region of the cytoplasmic domain participates in protein:protein interactions that allow the low density lipoprotein receptor to cluster in coated pits. PMID- 3104337 TI - Subcellular site of synthesis of the N-acetylgalactosamine (alpha 1-0) serine (or threonine) linkage in rat liver. AB - We have studied the subcellular site of synthesis of the GalNAc(alpha-1-0) Ser/Thr linkage in rat liver. The specific and total activities of polypeptide:N acetylgalactosaminyltransferase (using apomucin as exogenous acceptor) were highly enriched in membrane fractions derived from the Golgi apparatus; virtually no activity was detected in membranes from the rough and smooth endoplasmic reticulum. Vesicles of the above organelles (which were sealed and of the same membrane topographical orientation as in vivo) were able to translocate UDP GalNAc into their lumen in an assay in vitro; the initial translocation rate into Golgi vesicles was 4-6-fold higher than that into vesicles from the rough and smooth endoplasmic reticulum. Translocation of UDP-GalNAc into Golgi vesicles was temperature dependent and saturable with an apparent Km of 8-10 microM. UDP GalNAc labeled with different radioisotopes in the uridine and sugar was used to determine that the intact sugar nucleotide was being translocated in a reaction coupled to the exit of luminal UMP. Following translocation of UDP-GalNAc, transfer of GalNAc into endogenous macromolecular acceptors was detected in Golgi vesicles and not in those from the rough and smooth endoplasmic reticulum. The above results together with previous studies on the O-xylosylation of the linkage region of proteoglycans (Nuwayhid, N., Glaser, J.H., Johnson, J.C., Conrad, H.E., Hauser, S.C., and Hirschberg, C.B. (1986) J. Biol. Chem. 261, 12936-12941) strongly suggest that, in rat liver, the bulk of O-glycosylation reactions occur in the Golgi apparatus. PMID- 3104338 TI - Expression and characterization of human apolipoprotein A-I in Chinese hamster ovary cells. AB - We produced human apolipoprotein A-I (apoA-I) in Chinese hamster ovary (CHO) cells. The CHO cells were transfected with an expression plasmid which placed the human apoA-I gene under the direction of the human metallothionein II gene promoter. Isolation of a clonal cell line resulted in high level expression of apoA-I. Greater than 30% of total protein secreted by these CHO cells was apoA-I, which enabled us to purify apoA-I with a single step purification scheme. As a result, large quantities of apoA-I can be produced and isolated without having to rely on plasma sources. Structural characterization of the recombinant apoA-I showed it to be identical to authentic apoA-I from human serum high density lipoprotein. Furthermore, we demonstrated approximately equal to 90% of the apoA I secreted by CHO cells is processed, mature protein. A portion of the secreted recombinant apoA-I was associated with lipid and floated at a density approximately equal to 1.10 g/ml. Additional analysis identified the presence of five isoforms of apoA-I in the CHO cell conditioned medium. Processing and post translational modification of the recombinant apoA-I occurred in the CHO cell cultures in the absence of serum components. We conclude that the human apoA-I produced by CHO cells is identical to circulating, mature apoA-I in humans and that recombinant mammalian expression offers an opportunity to investigate apoA-I processing. PMID- 3104339 TI - Purification and characterization of human placental aromatase cytochrome P-450. AB - Aromatase cytochrome P-450, which catalyzes the conversion of androgens to estrogens, was purified from human placental microsomes. The enzyme was extracted with sodium cholate, fractionated by ammonium sulfate precipitation, and subjected to column chromatography in the presence of its substrate, androstenedione, and the nonionic detergent, Nonidet P-40. The preparation exhibits a single major band when analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and has a specific content of 11.5 nmol of P 450/mg of protein. The purified enzyme displays spectroscopic properties typical of the ferric and ferrous forms of cytochrome P-450. Full enzymatic activity can be reconstituted with rabbit liver microsomal cytochrome P-450 reductase and Nonidet P-40. Purified aromatase cytochrome P-450 displays catalytic characteristics similar to the enzyme in intact microsomes in the aromatization of androstenedione, 19-hydroxyandrostenedione and 19-oxoandrostenedione. Testosterone and 16 alpha-hydroxytestosterone are aromatized at maximal rates similar to androstenedione, and all substrates exhibit relative affinities corresponding to those observed in microsomes. We have raised rabbit antibodies to the purified enzyme which show considerable specificity and sensitivity on immunoblots. PMID- 3104340 TI - Evaluation of the single radial-immunodiffusion assay for measuring the glycoprotein content of rabies vaccines. AB - The glycoprotein content of rabies vaccines containing the Pitman-Moore strain of rabies virus was measured by the single radial immunodiffusion assay and correlated with vaccine potency. The variability of this assay was 6.3% for a single vaccine lot tested over a one-year period. Using sera prepared against rabies virus glycoprotein from different strains of virus, the assay gave different values. These differences could be eliminated by using a homologous vaccine strain as an internal reference. Single radial-immunodiffusion values for Pitman-Moore vaccines correlated with the manufacturers' NIH potency assay, but required a mathematical transformation to convert values from one assay to the other. Single radial-immunodiffusion values for Street Alabama Dufferin and Flury LEP vaccines did not correlate with NIH values. Modification of the single radial immunodiffusion technique and the feasibility of using this assay for the determination of rabies vaccine potency are discussed. PMID- 3104341 TI - The use of the firefly bioluminescent reaction for the rapid detection and counting of mycobacterium BCG. AB - A rapid test for the counting of Mycobacterium BCG, based on firefly luciferase assay of bacterial ATP has been evaluated. Three different methods for the extraction of ATP from mycobacterial cells were examined. Extraction with n butanol proved to be the best method. The amount of ATP extracted correlated well with the number of colony forming units. It was found that the ATP content per colony forming particle of BCG varied only slightly after various periods of cultivation. PMID- 3104342 TI - The effect of strain differences on the assay of rabies virus glycoprotein by single radial immunodiffusion. AB - Antigenic differences between rabies virus strains used for vaccine manufacture can be demonstrated using monoclonal antibodies. We have shown that these differences are sufficiently large to affect the potency values of vaccines measured in single radial immunodiffusion (SRD) assays if the reference and test vaccines are antigenically heterologous. The production of reagents for use in SRD assays for each strain of rabies virus should be considered. PMID- 3104343 TI - Quantitative estimation of diphtheria and tetanus toxoids. 2. Single radial immuno-diffusion tests (Mancini) and rocket immuno-electrophoresis test in comparison with the flocculation test. AB - The concentration in Lf units, of an unknown diphtheria or tetanus toxoid preparation is estimated in the flocculation test relative to reference preparations of tetanus and diphtheria antitoxins, respectively. By replacing the antitoxin reference preparations with toxoid reference preparations it should be possible to use immunological methods other than the flocculation test for the quantitative estimation of toxoids in Lf units. A number of diphtheria and tetanus toxoids were tested by rocket immuno-electrophoresis and single radial immuno-diffusion (Mancini test). The concentrations of the unknown toxoids were expressed relative to a diphtheria toxoid calibrated in Lf units (DIFT) and a tetanus toxoid calibrated in Lf units (TEFT), respectively. These two toxoid preparations are regarded as candidates for establishment as international standard preparations. The results obtained in the two tests were compared with those obtained in the flocculation test. In most cases the differences between the results did not exceed 10%. It is concluded, therefore, that the rocket electrophoresis or the radial immuno-diffusion tests can be used as alternatives to the flocculation test. PMID- 3104344 TI - The effects of different inactivating agents on the potency, toxicity and stability of pertussis vaccine. AB - The effect of heat (56 degrees C for 10 min), formaldehyde (0.1% at 37 degrees for 24h), glutaraldehyde (0.05% at room temperature for 10 min), thimerosal (0.02% at 37 degrees C for 24h), acetone-I (three treatments at room temperature) and acetone-II (three treatments at room temperature and fourth treatment at 37 degrees C), when used as inactivating agents in the preparation of pertussis suspension, was studied with regard to potency, toxicity and stability. Five batches each of Bordetella pertussis strains 134 and 509 were used for the study. The thimerosal inactivated pertussis (TIP) preparation was 1.5-2 times more potent than the heat inactivated pertussis (HIP) preparation. The potency values of the formaldehyde inactivated pertussis (TIP) and glutaraldehyde inactivated pertussis (GIP) preparations were similar to those of the HIP preparation, while the potencies of the acetone-I treated pertussis (A(I)TP) and acetone-II treated pertussis (A(II)TP) preparations were about half those of the HIP preparation. The FIP preparation was the least toxic showing maximum weight gain in the mouse weight-gain test (MGWT), while the TIP preparation did not pass the MWGT. The weight gains shown the GIP, A(I)TP and A(II)TP preparations were greater than those shown by the HIP preparation. The potency of pertussis component in the adsorbed diphtheria-pertussis-tetanus (DPT) vaccine was stable at 4-8 degrees C and 25 degrees C for three months for all types of pertussis vaccine. There was about 54-65% loss in the potency of the samples after three months at 35 degrees C. The inactivating agents used in the manufacture of pertussis preparations had no effect on the stability of the vaccine. PMID- 3104345 TI - Tumor promoting activity of teleocidin in skin and forestomach of mice initiated transplacentally with 7,12-dimethylbenz(a)anthracene. AB - Experiments on the effect of transplacental initiation with 7,12 dimethylbenz(a)anthracene (DMBA) and postnatal promotion with teleocidin were carried out in mice. The percentage of tumor-bearing mice among females treated with DMBA transplacentally on day 17 of gestation and postnatally by topical application of teleocidin to the skin of the back was 73.3% in week 30, whereas that among females treated with DMBA on day 10 of gestation and postnatally by topical application of teleocidin was 20.0%. This indicates that teleocidin shows potent tumor promoting activity on mouse skin in a transplacental initiation and postnatal promotion protocol. Furthermore, in the males treated with DMBA transplacentally on day 17 of gestation and given diet containing 0.01% teleocidin postnatally five tumors of the forestomach were found in 5 of 19 effective mice (26.3%) in week 52. One of these five tumors was a squamous cell carcinoma, and the others were papillomas. This indicates that teleocidin also has tumor promoting activity in the forestomach of mice. PMID- 3104347 TI - Influence of mesna and cysteine on the systemic toxicity and therapeutic efficacy of activated cyclophosphamide. AB - Presumably the coadministration of the uroprotector mesna in cyclophosphamide treatment does not influence the systemic activity of its activated metabolite. This was newly investigated in a mouse model. The LD50 values of i.p. administered mafosfamide, a derivative of act. CP, were increased by the simultaneous i.p. administration of mesna (mafosfamide: mesna 1:2 on a molar weight basis) from 590 mg/kg to 750 mg/kg, and after i.v. injection of cytostatic and thiol from 505 mg/kg to 810 mg/kg. Administration of 2 X molar cysteine i.v. or i.p. to mafosfamide-treated animals was even more effective against its lethal toxicity (LD50 i.p. 1800 mg/kg and i.v. 1130 mg/kg). Bone marrow toxicity (severe leukocytopenia) was partially abolished by both thiols. Also the therapeutic efficacy of act. CP against L1210 leukemia in DBA2 mice was reduced by 50% in the presence of cysteine and of mesna. Compared with mesna the higher detoxification effect of cysteine is attributed to its longer half-life (t1/2 20 min vs 12 min of mesna) and presumably an accumulation of cysteine in some cell systems (distribution coefficient 1.20 ml/g vs 0.68 ml/g of mesna). Nevertheless, our study clearly demonstrates a distinct systemic deactivation of act. CP by mesna, which might be of clinical relevance. PMID- 3104346 TI - Early changes in the arachidonic acid metabolism of HeLa cells in response to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and related compounds. AB - In order to search for possible mediators involved in the transient radiomimetic effectiveness of TPA and related compounds early changes in the AA metabolism of HeLa cells prelabeled with 1-14C-AA have been analyzed. Maximum release of AA with different concentrations of TPA (3 X 10(-9) to 3 X 10(-5) M) was observed after 2-3 h treatment in the presence of 10% calf serum. Released AA was reincorporated by the cells after that period, a phenomenon which was largely abolished or delayed by cycloheximide. Reincorporation of released AA was observed in the presence of 10% fresh serum as well as with 0.5% BSA, and appears to be due to an induction of responsible enzyme(s) by the phorbol ester. The earliest metabolites of AA produced via the cyclooxygenase such as PGE2 and PGF2 alpha and via lipoxygenases such as 12-, and 15-hydroxyeicosatetraenoic acids appear in small amounts and after later time points. AA release exhibited a pluriphasic dose response to TPA with maxima at 3 X 10(-8) M and greater than or equal to 10(-5) M. Comparative dose response measurements with respect to AA release were established using various promoting skin mitogens which exhibited the following order of potency: TPA greater than teleocidin approximately equal to RPA greater than mezerein much greater than EPA greater than 4-O-Me-TPA. For reasons discussed it appears unlikely that AA, Prostaglandins, or hydroxyeicosatetraenoic acid products play a significant role as mediators of the radiomimetic effects of TPA in G2 of the cell cycle. PMID- 3104348 TI - Reversal of defective lymphoproliferation in postoperative patients with colon cancer. AB - To establish a method for evaluation of immunological parameters in small blood samples, a whole blood technique was developed for the estimation of mitogen- or antigen-induced proliferation. Studies regarding cellular immunity in patients with colon cancer were done with 108 patients in all tumor stages, aged 32 to 80 years. They were studied before surgery and 10 days after operation. A group of 35 patients were further tested 3 months after surgical treatment. In patients with colon cancer the proliferative responses of peripheral blood lymphocytes to mitogens were significantly lower in comparison to healthy controls. These results were found when the response to concanavalin A, phytohemagglutinin, OKT 3, and pokeweed mitogen were analyzed preoperatively and 10 days postoperatively. There was no relation to the stage of disease. The marked reduction of mitogen responses was followed by a gradual return toward normal values 3 months after surgical resection of neoplastic growth in 80% of the patients. Our studies indicate that the defects were largely restored when testing was performed 3 months after operation. Using this result, it will be possible to perform long term studies in order to establish if there is a correlation between the return to normal immune reactivity and the survival of individual patients. PMID- 3104349 TI - Distinct localizations of urokinase-type plasminogen activator and its type 1 inhibitor under cultured human fibroblasts and sarcoma cells. AB - We studied the immunocytochemical localization of urokinase-type plasminogen activator (u-PA) and the type 1 plasminogen activator inhibitor (PAI-1) in human fibroblasts and sarcoma cells, using both polyclonal and monoclonal antibodies. The u-PA was found to be located at discrete cell-substratum contact sites, and also at areas of cell-cell contacts, whereas PAI-1 was distributed as a homogeneous carpet excluding strialike areas on the substrate under the cells. To confirm the extracellular localization of u-PA and PAI-1, we stained the cells live at 0 degree C before fixation. A double-labeling experiment showed different distribution of u-PA and PAI-1 under the cells, and especially their peripheral parts. The staining pattern of u-PA and PAI-1 resisted treatment with 0.2% saponin followed by mechanical removal of cells, a method previously reported to isolate focal contact membranes of fibroblasts. We further demonstrated the deposition of u-PA to the contact areas of cells obtained by saponin treatment by zymography, and that of PAI-1 by metabolic labeling, reverse zymography, immunoblotting, and immunoprecipitation. Fibronectin was also present in the preparations. The deposition of both PAI-1 and fibronectin by the sarcoma cells was enhanced, after treating the cells with 10(-6) M dexamethasone. The confinement of u-PA to discrete contact sites and the more uniform distribution of PAI-1 on the cell substratum may explain how cells producing large amounts of enzyme inhibitors can produce PA-mediated focal proteolysis. PMID- 3104350 TI - Hyaluronate synthetase inhibition by normal and transformed human fibroblasts during growth reduction. AB - To establish the relation of glycosaminoglycan synthesis to cell proliferation, we investigated the synthesis of individual glycosaminoglycan species by intact cells and in a cell-free system, using normal and transformed human fibroblasts under differing culture conditions. Reducing serum concentration brought about a marked decline in the synthesis of hyaluronate (HA) as well as cell proliferation on both normal and transformed cells. Both HA synthesis and proliferation decreased with increasing cell densities markedly (in inverse proportion to cell density) in normal cells but gradually in transformed cells. This noticeable congruity of the changes in HA synthesis and proliferation indicates that the change in HA synthesis is related primarily to cell proliferation rather than to cell density or cellular transformation. Examination of HA synthesis in a cell free system demonstrated that the activity of HA synthetase also fluctuated in conjunction with cell proliferation. Furthermore, growth-reduced cells (except crowded transformed cells) inhibited cell-free HA synthesis and this inhibition was induced coincidentally with a decrease in both HA synthetase activity and proliferation. These findings suggest that the change in HA synthesis is significant in the regulation of cell proliferation. PMID- 3104351 TI - A mitotic form of the Golgi apparatus in HeLa cells. AB - Galactosyltransferase, a marker for trans-Golgi cisternae in interphase cells, was localized in mitotic HeLa cells embedded in Lowicryl K4M by immunoelectron microscopy. Specific labeling was found only over multivesicular structures that we term Golgi clusters. Unlike Golgi stacks in interphase cells, these clusters lacked elongated cisternae and ordered stacking of their components but did comprise two distinct regions, one containing electron-lucent vesicles and the other, smaller, vesiculo-tubular structures. Labeling for galactosyltransferase was found predominantly over the latter region. Both structures were embedded in a dense matrix that excluded ribosomes and the cluster was often bounded by cisternae of the rough endoplasmic reticulum, sometimes on all sides. Clusters were present at all stages of mitosis examined, which included prometaphase, metaphase, and telophase. They were also identified in conventionally processed mitotic cells and shown to contain another trans-Golgi marker, thiamine pyrophosphatase. Serial sectioning showed that clusters were discrete and globular and multiple copies appeared to be dispersed in the cytoplasm. Their possible role in the division of the Golgi apparatus is discussed. PMID- 3104352 TI - Stimulus-specific induction of phospholipid and arachidonic acid metabolism in human neutrophils. AB - Phospholipid remodeling resulting in arachidonic acid (AA) release and metabolism in human neutrophils stimulated by calcium ionophore A23187 has been extensively studied, while data obtained using physiologically relevant stimuli is limited. Opsonized zymosan and immune complexes induced stimulus-specific alterations in lipid metabolism that were different from those induced by A23187. [3H]AA release correlated with activation of phospholipase A2 (PLA2) but not with cellular activation as indicated by superoxide generation. The latter correlated more with calcium-dependent phospholipase C (PLC) activation and elevation of cellular diacylglycerol (DAG) levels. When cells that had been allowed to incorporate [3H]AA were stimulated with A23187, large amounts of labeled AA was released, most of which was metabolized to 5-HETE and leukotriene B4. Stimulation with immune complexes also resulted in the release of [3H]AA but this released radiolabeled AA was not metabolized. In contrast, stimulation with opsonized zymosan induced no detectable release of [3H]AA. Analysis of [3H]AA-labeled lipids in resting cells indicated that the greatest amount of label was incorporated into the phosphatidylinositol (PI) pool, followed closely by phosphatidylcholine and phosphatidylserine, while little [3H]AA was detected in the phosphatidylethanolamine pool. During stimulation with A23187, a significant decrease in labeled PI occurred and labeled free fatty acid in the pellet increased. With immune complexes, only a small decrease was seen in labeled PI while the free fatty acid in the pellets was unchanged. In contrast, opsonized zymosan decreased labeled PI, and increased labeled DAG. Phospholipase activity in homogenates from human neutrophils was also assayed. A23187 and immune complexes, but not zymosan, significantly enhanced PLA2 activity in the cell homogenates. On the other hand, PLC activity was enhanced by zymosan and immune complexes. Stimulated increases in PLC activity correlated with enhanced superoxide generation induced by the stimulus. PMID- 3104353 TI - Relationship of thrombin-stimulated arachidonic acid release and metabolism to mitogenesis and phosphatidylinositol synthesis. AB - Thrombin and certain prostaglandins are both capable of stimulating the proliferation of cultured cells. Since thrombin stimulates the release and metabolism of arachidonic acid, the precursor of prostaglandins, we examined the relationship between this release and metabolism and the stimulation of cell division in cultured fibroblasts. We also examined the role of prostaglandin synthesis in thrombin-stimulated phosphatidylinositol synthesis. The data in this report demonstrate that the release and metabolism of arachidonic acid are not necessary for thrombin-stimulated cell division. The presence of a low concentration of chymotrypsin prevented thrombin-stimulated arachidonic acid release and metabolism without affecting the stimulation of cell division. Furthermore, thrombin-stimulated cell division occurred in the presence of indomethacin concentrations that prevented cyclooxygenase-mediated metabolism of arachidonic acid. The following experiments showed that thrombin-stimulated phosphatidylinositol synthesis was brought about by a cyclooxygenase-mediated metabolite(s) of arachidonic acid. Indomethacin inhibited the cyclooxygenase mediated metabolism of arachidonic acid without affecting the thrombin-stimulated release of arachidonic acid. Indomethacin also inhibited thrombin-stimulated phosphatidylinositol synthesis. The dose dependence of this inhibition paralleled the inhibition by indomethacin of cyclooxygenase-mediated metabolism of arachidonic acid. In addition, prostaglandin F2 alpha stimulated phosphatidylinositol synthesis in the presence of indomethacin concentrations which prevented thrombin-stimulated phosphatidylinositol synthesis. PMID- 3104354 TI - Regional differences in arachidonic acid release in rat hippocampal CA1 and CA3 regions during cerebral ischemia. AB - Changes in the levels of arachidonic acid during ischemia in selectively vulnerable areas of the hippocampus were studied in the rat brain. Since neurons in the CA1 region are more vulnerable to ischemia than neurons in the adjacent CA3 region, the release of arachidonic acid in these two regions was measured during decapitation ischemia of 4- to 12-min duration. The concentration of free arachidonic acid increased with the duration of ischemia in both regions. However, the level was significantly higher in CA1 than in CA3 after 8 and 12 min of ischemia. This difference in arachidonic acid accumulation may reflect differences between the regions in agonist-dependent phospholipid breakdown as well as calcium-dependent phospholipase activity. The importance for the development of neuronal necrosis is discussed. PMID- 3104355 TI - Regional cerebral metabolic activity in the rat following experimental subarachnoid hemorrhage. AB - A new experimental model was employed to investigate alterations of cerebral metabolic activity in rats subjected to extensive subarachnoid hemorrhage (SAH). The hemorrhages were produced in anesthetized animals by inserting 0.37 ml fresh autologous arterial blood into the subarachnoid space. Rats that underwent sham operations received subarachnoid injections of mock CSF to study the effects of sudden raised intracranial pressure (ICP). Forty-eight hours after subarachnoid injection, the unanesthetized rats were given intravenous injections of [14C]2 deoxyglucose. Experiments were terminated 45 min later by decapitation, and the brains were removed and frozen. Regional brain metabolic activity was studied employing quantitative autoradiography. In comparison with control animals, cerebral metabolic activity was diffusely decreased following SAH. Statistically significant decreases in metabolic activity of less than 34% were observed in 17 of 30 brain regions studied. The largest percentage reductions were in regions displaying the highest basal metabolic rates. Subarachnoid injections of mock CSF also produced depression of cerebral metabolic activity, but quantitatively these changes were not as pronounced as in the hemorrhage group. These studies demonstrate regional changes in brain function following SAH. The data relate these changes to both the presence of blood in the subarachnoid space and sudden raised ICP. PMID- 3104356 TI - Parkinson's disease: evaluation and therapeutic strategy. PMID- 3104358 TI - AIDS and hemophilia: a cruel paradox. PMID- 3104357 TI - An elderly man with shoulder pain, dyspnea. PMID- 3104359 TI - Osteoporosis and 'affluent' diet. PMID- 3104360 TI - Ectopic hormonal syndromes in neoplastic disease. PMID- 3104361 TI - Hypercholesterolemia. Dietary and pharmacotherapy. PMID- 3104362 TI - Tolerating uncertainty. PMID- 3104363 TI - Diagnosis and management of ovarian cancer. PMID- 3104364 TI - Brain death in a murder victim: a medicolegal dilemma. PMID- 3104365 TI - The diabetic baby who got better. PMID- 3104367 TI - Humanism in medicine. PMID- 3104366 TI - Second-degree heart block after spontaneous abortion. PMID- 3104369 TI - Inflammation: Khartoum to Casablanca. PMID- 3104368 TI - Selecting an appropriate NSAID. PMID- 3104370 TI - What is the cause of incomplete right bundle branch block? PMID- 3104371 TI - Therapist-assisted versus self-help relaxation treatment of chronic headaches in adolescents: a school-based intervention. AB - This study compared the relative efficacy of a therapist-assisted relaxation treatment programme with a self-help approach and a self-monitoring condition in the treatment of chronic headaches in adolescents within a school setting. The subjects were 46 high school students, 16-18 years of age, who were randomly assigned to the three treatment conditions. The results indicated that the self help approach was as effective as the therapist-assisted relaxation condition in reducing the students' headache, and that these findings were maintained at a 5 month follow-up evaluation. The results suggest that the self-help relaxation procedure is a potential low-cost alternative treatment to a more traditional therapist-based intervention condition. PMID- 3104372 TI - Mass spectrometric evidence for the conversion of exogenous adrenate to dihomo prostaglandins by seminal vesicle cyclo-oxygenase. A comparative study of two animal species. AB - We present conclusive mass spectrometric evidence for the synthesis of 1a,1b dihomoprostaglandin E2 and 1a,1b-dihomoprostaglandin F2 alpha by sheep seminal vesicle microsomes and swine whole vesicular homogenates. Swine microsomes prepared according to standard procedure were catalytically inactive, possibly due to autoinactivation of the cyclo-oxygenase caused by metabolism of endogenous substrate released during the isolation procedure. Cyclo-oxygenase activity could be demonstrated, however, when the porcine vesicles were homogenized in the presence of exogenous substrate. Chemical and mass spectrometric evidence presented here allow unequivocal structural assignments. PMID- 3104373 TI - Determination of 15NH3 by gas chromatography-mass spectrometry. Application to the measurement of putrescine oxidation by human plasma. AB - A convenient and sensitive method for the determination of 15NH3 has been developed. Ammonia was purified from sample solutions by a modified microdiffusion method, derivatized with pentafluorobenzoyl chloride to pentafluorobenzamide (PFBA) and determined by gas chromatography-mass spectrometry using a multiple ion detector. PFBA was eluted from the gas chromatographic column within 2 min and resulted in a simple mass fragmentation pattern. The 15N/14N ratio was accurately determined with picomole amounts of PFBA by measuring the molecular ions of PFBA and [15N]PFBA. The method was applied to the assay of putrescine oxidation by human plasma. 15NH3 was produced by incubating 15N-labelled putrescine with plasma. The 15NH3 production was time dependent and strongly inhibited by the addition of aminoguanidine, an inhibitor of diamine oxidase. Exceedingly high 15NH3 production from [15N]putrescine was observed in the plasma from pregnant women. In contrast, only trace amounts of 15NH3 were formed in the plasma from normal men and non-pregnant women. The method seems to be applicable to various biological systems that produce ammonia as a metabolic product. PMID- 3104374 TI - Separation and quantitation of bacterial ribonucleoside triphosphates extracted with trifluoroacetic acid, by anion-exchange high-performance liquid chromatography. AB - Endogenous ribonucleoside triphosphates were determined in Escherichia coli and Pseudomonas aeruginosa by using anion-exchange high-performance liquid chromatography after extraction with trifluoroacetic acid (TFA). Results indicate that in E. coli this extraction method is more sensitive and reliable than trichloroacetic acid (TCA) and formic acid extraction. However, whereas in P. aeruginosa best yields of adenosine 5'-triphosphate and guanosine 5'-triphosphate are obtained following extraction with TFA, the yields of uridine 5'-triphosphate and cytidine 5'-triphosphate can be increased if extraction is performed with TCA. PMID- 3104375 TI - Simultaneous measurement of urinary and plasma norepinephrine, epinephrine, dopamine, dihydroxyphenylalanine, and dihydroxyphenylacetic acid by coupled column high-performance liquid chromatography on C8 and C18 stationary phases. AB - This paper describes a simple and sensitive method for measuring norepinephrine, epinephrine, dopamine, dihydroxyphenylalanine, and dihydroxyphenylacetic acid in urine and plasma. This method involves a two-stage frontal-chromatographic clean up, followed by coupled minibore high-performance liquid chromatography with electrochemical detection. The use of phenylboronate instead of alumina yields recoveries in the range of 80-90% for all the catecholamines, dihydroxyphenylalanine and dihydroxyphenylacetic acid without interferences. The interassay coefficient of variation for the measurement of these compounds was less than 12%. PMID- 3104376 TI - Gradient and isocratic high-performance liquid chromatography of proteins on a new agarose-based anion exchanger. AB - We describe a new, simple, and mild method for the preparation of anion exchangers, based on the coupling of alkylamines to epoxy-activated agarose (prepared by the reaction of agarose with butanediol diglycidyl ether). Since a polar OH-group is formed when an epoxide reacts with an OH or NH2 group, the ion exchanger did not show any hydrophobic interaction. This is important, since it may be impossible to desorb a protein from an ion exchanger having a hydrophobic character, because increasing the salt concentration of the eluent to decrease the electrostatic binding inevitably strengthens the hydrophobic interaction. By the method described, 3-diethylamino-2-hydroxy-propyl agarose (DEAHP-agarose) was prepared. High resolution of proteins was obtained by gradient elution at both high and low degrees of substitution. However, isocratic separations required a low degree of substitution, in accordance with a hypothesis previously put forward in connection with a theoretical and experimental study of the conditions for isocratic elution of macromolecules on amphiphilic gels. A study of the retention times of several proteins at different pH levels and buffer compositions indicated that different pH levels should be tested for maximal resolution and that, in many cases, the best resolution can be obtained if the DEAHP-agarose is operated in a buffer containing sodium acetate instead of sodium chloride. A quaternary amine agarose, 3-methyldiethylamino-2-hydroxy-propyl agarose (QAE-agarose), can be synthesized easily from DEAHP-agarose by alkylation with methyl iodide. The titration curves of DEAHP-agarose and QAE-agarose showed pK values around 9.5 and 11.3, respectively. PMID- 3104377 TI - Integrated biological-physicochemical system for the identification of antitumor compounds in fermentation broths. AB - A rapid, integrated biological-physicochemical system for the identification of six major classes of antitumor compounds in fermentation broths is described. The system relies upon preliminary fractionation of the fermentation broth by liquid solid extraction, gradient high-performance liquid chromatography with diode array spectrophotometric detection of the compounds and automated bioassay. The previously stored UV-VIS spectra of the biologically active peaks are used for identification. Confirmation of compound identity is by thermospray liquid chromatography-mass spectrometry. The method has been applied to representatives of the bleomycin, streptonigrin, echinomycin, chromomycin, actinomycin and anthracycline groups. PMID- 3104378 TI - Liquid chromatographic method for the determination of 3,4 dihydroxyphenylethylene glycol and 3,4-dihydroxymandelic acid in plasma. AB - A method is described for the simultaneous determination of the deaminated catecholamine metabolites 3,4-dihydroxyphenylethylene glycol (DOPEG) and 3,4 dihydroxymandelic acid (DOMA) in plasma by liquid chromatography with amperometric detection. The compounds are extracted from plasma by adsorption on alumina, then separated on a reversed-phase column coated with tributyl phosphate as the stationary liquid phase. It is a simple and selective method that permits the determination of basal levels of DOPEG and DOMA in plasma with a relative standard deviation of 3%. PMID- 3104379 TI - Dual-column determination of albumin and immunoglobulin G in serum by high performance affinity chromatography. AB - High-performance affinity chromatography was used for the simultaneous determination of albumin and immunoglobulin G in serum. Two columns in series, the first containing immobilized anti-albumin antibodies and the other containing protein A for binding immunoglobulin G, were eluted separately at pH 3 by means of a column-switching system. This method gave results in good agreement with commercially available methods, while requiring only 2 microliter of serum and 6.0 min per cycle. It was shown that albumin and immunoglobulin G were selectively retained, with little interference from other components, including immunoglobulins A and M. PMID- 3104380 TI - Purification procedure for peptide toxins from the cyanobacterium Microcystis aeruginosa involving high-performance thin-layer chromatography. PMID- 3104381 TI - Quantitative determination of carbaryl and carbaryl metabolites by reversed-phase high-performance liquid chromatography. PMID- 3104382 TI - Determination of the two dinitrate metabolites of nitroglycerin in human plasma by capillary gas chromatography with electron-capture detection. AB - This paper describes a sensitive method for the specific determination of 1,2 glyceryl dinitrate and 1,3-glyceryl dinitrate as metabolites of nitroglycerin at concentrations down to 250 pg/ml plasma. After addition of a known amount of 2 isosorbide mononitrate as internal standard, plasma is introduced onto an Extrelut cartridge and the compounds of interest are eluted with dichloromethane. The glyceryl dinitrates are then quantitated by capillary gas chromatography with electron-capture detection. PMID- 3104383 TI - Rapid and sensitive method for measurement of hyaluronic acid and isomeric chondroitin sulfates using high-performance liquid chromatography. AB - A high-performance liquid chromatographic method for the separation and analysis of the unsaturated tetrasaccharide and hexasaccharide from Streptomyces hyaluronidase (S.HAase) enzyme digestion products of hyaluronic acid (HA) and standard unsaturated disaccharides 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4 enepyranosyluronic acid)-D-galactose (delta Di-0S), 2-acetamido-2-deoxy-3-O-(beta D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (delta Di-4S) and 2 acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D galactose (delta Di-6S) is described. An amino phase chemically bonded to silica with a particle diameter of 6 micron was used as the column. The composition and the pH of the mobile phase were systematically varied to determine the optimal chromatographic conditions for separation and analysis of the compounds. For HA, a complete separation was accomplished in less than 12 min with a practical detection limit of 100 ng. Separation of the disaccharides also required less than 15 min with detection limits of 10 ng for delta Di-0S and 25 ng each for delta Di-4S and delta Di-6S. This chromatographic method represents a significant improvement over existing methods. It allows the simultaneous separation and analysis of HA and chondroitin sulfate isomers (after digestion of the latter with chondroitinase) at a higher speed, and with more sensitivity and efficiency. PMID- 3104384 TI - Gas chromatographic assay of glycerol mononitrates in biological samples. AB - A new gas chromatographic analysis of glycerol 1-nitrate and glycerol 2-nitrate is described. The method is suitable for a variety of biological samples and can detect down to the low nanogram range. An extract of the sample to be analysed is treated with phenylboronic acid. The glycerol mononitrates rapidly form cyclic boronates, with five- and six-membered rings, respectively, which can then be separated by gas chromatography and detected by an electron-capture detector. PMID- 3104385 TI - Simultaneous determination of carbohydrates and products of carbohydrate metabolism in fermentation mixtures by HPLC. AB - An improved procedure for separating and quantitating carbohydrates, alcohols, and organic acids in fermentation mixtures metabolized by intestinal microflora is described. The high-pressure liquid chromatographic method is efficient, reproducible, and sensitive. A column packed with cation-exchange resin in the hydrogen form, eluted isocratically with 0.028 M H2SO4 at 40 degrees C separates the compounds of interest. The eluate is monitored with ultraviolet and refractive index detectors in series. On-line acquistion and storage of detector output by a computer allows post-analysis data manipulation and quantitation. Using this method, the metabolic profiles for the fermentation of glucose, fructose, lactose, and sucrose by several intestinal microorganisms are characterized and compared. PMID- 3104386 TI - The effect of cost sharing on the use of antibiotics in ambulatory care: results from a population-based randomized controlled trial. AB - Little is known about how generosity of insurance and population characteristics affect quantity or appropriateness of antibiotic use. Using insurance claims for antibiotics from 5765 non-elderly people who lived in six sites in the United States and were randomly assigned to insurance plans varying by level of cost sharing, we describe how antibiotic use varies by insurance plan, diagnosis and health status, geographic area, and demographic characteristics. People with free medical care used 85% more antibiotics than those required to pay some portion of their medical bills (controlling for all other variables). Antibiotic use was significantly more common among women, the very young, patients with poorer health, and persons with higher income. Use of antibiotics for viral, viral bacterial, and bacterial conditions did not differ between free and cost-sharing insurance plans, given antibiotics were the treatment of choice. Cost sharing reduced inappropriate and appropriate antibiotic use to a similar degree. PMID- 3104387 TI - Gonadotropins and testosterone escape from suppression during prolonged luteinizing hormone-releasing hormone antagonist administration in normal men. AB - The ability of prolonged administration of a LHRH antagonist, [Ac-delta 3Pro1,4F D-Phe2,D-Trp3,6]LHRH (4F-antagonist), to suppress serum gonadotropin and testosterone levels was studied in normal men. The 4F-antagonist was given either as a continuous 13.3 micrograms/kg X h sc infusion for 72 h or as intermittent sc injections of 100 micrograms/kg every 6 h for 7 days. Serum FSH, LH, and testosterone levels decreased in the period immediately following initiation of 4F-antagonist administration. However, an escape toward baseline levels for each of these hormones occurred during prolonged antagonist administration. When men receiving the continuous infusion were challenged with iv bolus doses of 50 micrograms LHRH, the response of LH after the first 12 h of 4F-antagonist administration was similar to that before its administration. This gonadotropin and testosterone escape suggests that, at the doses used, the inhibitory action of the antagonist on gonadotropin secretion is progressively lost. The initial decrease in androgen levels could serve to augment endogenous LHRH release, which, in turn, overcomes the pituitary effects of the antagonist, or to augment endogenous LH secretion directly. These results demonstrate that the pituitary can escape from the suppressive effects of prolonged LHRH antagonist administration and partially restore serum gonadotropin and testosterone levels to normal in man. PMID- 3104388 TI - Suppression of pituitary-gonadal function by a potent new luteinizing hormone releasing hormone antagonist in normal men. AB - LHRH antagonists compete with endogenous LHRH for binding to receptors on pituitary gonadotrophs and thereby inhibit gonadal function by suppressing gonadotropin secretion. We studied the effects of a recently developed LHRH antagonist on the pituitary-gonadal axis in man. The antagonist Detirelix [( N-Ac D-Nal(2)1, D-pCl-Phe2,D-Trp3, D-hArg(Et2)6, D-Ala10]LHRH) was given as a single sc injection to nine normal men at three dose levels (5, 10, and 20 mg) at intervals of at least 7 days. Serum FSH, LH, and testosterone levels were measured before treatment, at frequent intervals for 48 h, and 72, 96, and 168 h after administration of the antagonist. Mean serum FSH levels decreased (P less than 0.001) from 6.9 +/- 0.5 (+/- SEM) mIU/mL to nadirs of 4.4 +/- 1.1, 3.6 +/- 0.9, and 4.1 +/- 0.9 after the 5-, 10-, and 20-mg doses, respectively. Serum LH levels decreased (P less than 0.001) from 6.2 +/- 0.3 mIU/mL to nadirs of 3.3 +/- 0.4, 2.8 +/- 0.3, and 2.7 +/- 0.3 after all three doses. Serum testosterone levels decreased (P less than 0.001) in a dose-dependent fashion from 5.1 +/- 0.2 ng/mL to nadirs of 1.3 +/- 0.3, 0.9 +/- 0.3, and 0.6 +/- 0.1 after the same doses. After the initial testosterone decrease, however, escape occurred 12-28 h after the lower doses. The area under the response curve, describing hormone concentrations as a function of time during the study, diminished by 23 +/- 2%, 36 +/- 4%, and 36 +/- 3% for FSH, by 14 +/- 6%, 30% +/- 6%, and 34 +/- 5% for LH, and by 41 +/- 5%, 58 +/- 6%, and 68 +/- 4% for testosterone with the same doses, respectively. The apparent plasma disappearance half-life of Detirelix by RIA was at least 41 h after all three doses. Detirelix elicited only a minor local reaction; no systemic side-effects were observed within the dose range used. These results indicate that this LHRH antagonist is a safe, highly potent inhibitor of the human pituitary-gonadal axis with an exceptionally long duration of action. PMID- 3104389 TI - Dynamics of plasma gonadotropin and sex steroid release in polycystic ovarian disease after pituitary-ovarian inhibition with an analog of gonadotropin releasing hormone. AB - To assess the dynamics of the suppression and recovery of plasma gonadotropins and sex steroids during and after inhibition of pituitary-ovarian function by a long-acting agonist GnRH-analog (GnRH-A), eight patients with polycystic ovarian disease were treated with 12 micrograms/kg X day GnRH-A for 56 consecutive days. In response to GnRH-A, these patients had a sharp and pronounced decline of their initially elevated immunoreactive LH and bioactive LH (bioLH) levels. Plasma immunoreactive FSH levels declined more rapidly than did bioLH, but the FSH decline was less sustained. Plasma testosterone, androstenedione, and estrone (E1) levels also declined during GnRH-A administration. The pattern of plasma androgen decrease resembled that of bioLH. There was a positive correlation between bioLH and the two androgens (r = 0.85; P less than 0.05, by Spearman's rank correlation, for both hormones). Cessation of GnRH-A administration was followed by prompt progressive increases in gonadotropin and androgen concentrations to pretreatment values. FSH recovered faster than bioLH. BioLH plasma concentrations reached pretreatment values by day 28. The recovery of plasma androstenedione and testosterone levels correlated positively with that of bioLH. Although plasma E1 levels were higher during the recovery period than during treatment, they never reached the concentrations found during the basal period, whereas estradiol concentrations were slightly but not significantly higher than those in the basal period. As a consequence, the E1 to estradiol ratio, very high in the basal period, approximated unity during recovery. These data indicate that hyperandrogenism in polycystic ovarian disease is gonadotropin dependent and accompanied by a relative abundance of LH bioactivity basally and during GnRH-A administration. Thus, the relative increase in bioLH secretion appears to be independent of the rate of gonadotropin secretion and the circulating sex steroid concentrations. PMID- 3104390 TI - Alterations in cytotoxic and phenotypic subsets of natural killer cells in acquired immune deficiency syndrome (AIDS). AB - Testing of cytotoxic function using a panel of natural killer (NK)-sensitive target cells, including a unique herpes simplex virus-infected Raji-cell target, was performed in conjunction with phenotypic cell analysis by dual-color flow cytometry to characterize the NK system. Subjects included in the study were at risk for or infected with the etiologic agent of the acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV). A generalized defect in NK function was temporally correlated with disease manifestations, as evidenced by deficient NK lytic function in patients with AIDS and AIDS-related complex (ARC). Healthy at-risk subjects, including those seropositive for HIV, exhibited robust NK-cell function. Phenotypic analysis revealed that normal proportions of the NK associated CD16+ (Leu11) Leu7- and CD16+(Leu11)Leu7+ lymphocyte subsets were maintained throughout the clinical progression of HIV infection. However, the proportion and numbers of cells of the CD8+(Leu2)Leu7+ subset were increased in AIDS, ARC, and healthy at-risk subjects, including those seronegative for HIV. These results are consistent with a qualitative defect in the NK system in AIDS, perhaps secondary to CD4-cell depletion and a concomitant lack of essential accessory factors. The elevation in CD8+(Leu2)/Leu7+ cells is not solely the result of HIV infection and may be a general response to viruses and/or other antigenic stimulation. PMID- 3104391 TI - Combined evaluation of circulating immune complexes and antibodies to Pseudomonas aeruginosa as an immunologic profile in relation to pulmonary function in cystic fibrosis. AB - We developed a solid-phase radioimmunoassay with a reference standard pseudomonas antigen and used this with 125I-labeled anti-human immunoglobulin to evaluate specific antibodies to Pseudomonas aeruginosa, qualitatively and quantitatively, in sera from children with cystic fibrosis (CF) whose lungs were colonized by this bacterium. The results of this IgG assay correlated with the number of precipitin antibodies to the standard reference antigen determined by cross immunoelectrophoresis in the same sera. Forced expiratory volume (FEV1; percentage predicted), determined as an indicator of lung injury in CF, was evaluated as an immunologic response to pseudomonas, against a profile derived from combined serial data on both the circulating immune complexes (CIC) and the Ps. aeruginosa antibodies (N = 25 CF patients; 108 sera). This revealed that in CF patients who had no specific IgG antibodies to Ps. aeruginosa and no IgG-CIC had the best pulmonary function (FEV1 = 115 +/- 14.52%) and those with high levels of antibodies to this organism and high IgG-CIC levels had the poorest lung function (FEV1 = 69.75 +/- 10.99%) (P less than 0.05). We believe that this indicates an immunologic basis for lung injury in cystic fibrosis. PMID- 3104392 TI - Peripheral blood mononuclear-cell interleukin-2 production, receptor generation and lymphokine-activated cytotoxicity in inflammatory bowel disease. AB - The interleukin-2 pathway is essential for the normal immune response to antigen stimulation; we have examined the possibility that this may underlie abnormal peripheral blood lymphocyte immunoregulatory function that has been observed in patients with inflammatory bowel disease. We studied 11 patients with Crohn's disease and 5 with ulcerative colitis, all with quiescent disease activity. Peripheral blood mononuclear cells were isolated from these patients and from healthy age- and sex-matched controls. Interleukin-2 production after mitogen and phorbol-myristate acetate stimulation was similar in both groups: 381 +/- 71 (mean +/- SE) U/ml by control cells and 451 +/- 70 by patient cells. Interleukin 2 receptor generation was also measured pre- and poststimulation by labeling with anti-Tac antibody. This was 10.45 +/- 1 and 69.95 +/- 3.85% for control cells and 11.41 +/- 1.38 and 60.9 +/- 4.25% for patients cells. Finally, we examined the response of these cells to interleukin-2 stimulation by generating cells with direct cytotoxicity to 51Cr-labeled Daudi-cell targets. Control cells caused 59.5 +/- 46% 51Cr release, whereas patient cells caused 50.8 +/- 5.18% release. None of the above results achieved statistical significance. We conclude that the peripheral blood interleukin-2 pathway is normal in inactive inflammatory bowel disease. PMID- 3104394 TI - Steroid profiles during cycles with HCG stimulation of luteal function during in vitro fertilization cycles. AB - 178 in-vitro fertilization cycles have been explored for luteal function. Clomiphene and human menopausal gonadotrophins were used for ovarian stimulation and some patients were supplemented with human chorionic gonadotrophin (HCG) (5000 IU) on the day of laparoscopy, and also 2 and 4 days later. An imbalance of luteal function was observed in non-supplemented stimulated cycles, with hyperoestrogenicity and a relatively low production of progesterone. The administration of HCG reduced this imbalance by improving the production of progesterone without affecting the production of oestradiol-17 beta. PMID- 3104395 TI - Observations on 767 clinical pregnancies and 500 births after human in-vitro fertilization. AB - Details of 767 clinical pregnancies and 500 births from Bourn Hall are reported. All treated patients included some over 40 years old, many with ovarian or uterine defects, male infertility, etc. Patients were treated during their natural cycle or stimulated with clomiphene or clomiphene and human menopausal gonadotrophin. Follicular maturation was induced by an endogenous luteinizing hormone surge or human chorionic gonadotrophin. A maximum of three embryos were replaced, except in a few patients receiving four. Twenty-eight percent of pregnancies aborted, occurring more frequently in patients who were over 40, with a complicated obstetric history, and given clomiphene alone. Approximately 18% of fetuses 'vanished' in multi-pregnancies. Seventy-one sets of binovular twins and nine sets of triplets have been born, and seven twins and three triplets are ongoing. Seventeen and a half per cent of patients aged 39 and less with one or more replaced embryos delivered one or more children, rising to almost 25% with three replaced embryos. A mean of 1.3 children were born per delivery when three embryos were replaced. Most deliveries were by Caesarean section. There were two cases of placenta praevia, one stillbirth, four major and eight minor anomalies. All the triplets, and some twins and singletons had low birth weights and were born prematurely. The sex ratio was 247 males to 253 females. PMID- 3104393 TI - Pulmonary alveolar macrophages in patients with sarcoidosis and hypersensitivity pneumonitis: characterization by monoclonal antibodies. AB - Using a panel of monoclonal antibodies (MoAbs), the frequency of cells bearing Class I and Class II major histocompatibility complex (MHC) determinants, transferrin receptor (TR) sites, and interleukin-2 receptors (IL-2R) has been evaluated on pulmonary alveolar macrophages (PAM) recovered from the bronchoalveolar lavage (BAL) fluid of 21 patients with pulmonary sarcoidosis (including 11 cases with active sarcoidosis and 10 cases with inactive disease), 8 patients with hypersensitivity pneumonitis (HP), and 6 normal non-smoking volunteers. When the frequency of Class II DR-positive cells was considered, 64.3% of control PAM expressed HLA-DR products. No statistically significant differences were observed between controls and sarcoid patients, while HP patients showed an enhanced proportion of DR+ PAM with respect to normal PAM (P less than 0.05). On the contrary, the frequency of PAM expressing HLA-DQ molecules was higher in both active sarcoidosis and HP patients with respect to patients with inactive sarcoidosis and normal subjects (P less than 0.001). A statistically significant increase in Class I antigen-positive PAM has been demonstrated in HP patients as compared to controls (P less than 0.05). Active sarcoid patients showed a higher number of PAM-bearing TR sites than controls and other groups of patients considered (P less than 0.001). An increase in the percentage of IL-2R-positive PAM has been demonstrated in active sarcoidosis (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104396 TI - Effects of oestradiol and progesterone on the synthesis of DNA and the anti haemophilic factor VIII antigen in human endometrial endothelial cells in vitro: a pilot study. AB - The effect of various concentrations of oestradiol and progesterone on DNA synthesis in endometrial endothelial cells derived from human decidua has been studied in vitro by means of a microfluorometric technique and [3H]thymidine incorporation. Oestradiol in concentrations of 10-40 ng/ml was found to significantly stimulate DNA synthesis in the cells whereas progesterone significantly decreased the incorporation of [3H]thymidine. A highly significant correlation (P less than 0.01) was found in the oestrogen-treated samples between the [3H]thymidine incorporation and the ethidium bromide fluorescence after the removal of RNA. No such correlation was found in the progesterone-treated samples. A microfluorometric assessment of the anti-haemophilic antigen Factor VIII following immunofluorescence labelling suggested an increase in the synthesis of this factor after oestradiol treatment whereas progesterone administration did not show any effect. Although no direct extrapolation can be made from the results of the in vitro studies to in vivo conditions the endothelial cell culture system provides a useful model for testing the effect of mitotic mediators and compounds interfering with intracellular protein synthesis. It may therefore contribute to a better understanding of the bleeding mechanism. PMID- 3104397 TI - Comparison between clomiphene plus pulsatile human menopausal gonadotrophin and clomiphene plus pulsatile follicle stimulating hormone in induction of multiple follicular development in women. AB - Eighteen normally cycling women with tubal infertility undergoing in-vitro fertilization and embryo transfer were treated with clomiphene only (nine cycles), clomiphene plus human menopausal gonadotrophin (HMG) (18 cycles) and clomiphene plus follicle-stimulating hormone (FSH) (12 cycles). Clomiphene was given from day 2 to 6 (150 mg daily). HMG and FSH were injected s.c. in a pulsatile manner via a pump (28 IU every 3 h). Plasma FSH and oestradiol levels and the number of follicles greater than or equal to 16 mm in diameter were similar in the clomiphene/HMG and the clomiphene/FSH cycles, but significantly higher than in the clomiphene-only cycles. In contrast, luteinizing hormone and progesterone levels during the treatment did not differ significantly among the three regimens. Twelve of the 18 women were treated with clomiphene/HMG in one cycle and clomiphene/FSH in another and eight of them with clomiphene only in a third cycle (a total of 32 cycles). In the clomiphene/HMG cycle seven of these 12 women (58%) had plasma FSH levels during treatment similar to those in the clomiphene/FSH cycle and six of them (86%) had the same number of follicles in both cycles. A significant, but not very strong correlation was found between FSH treatment levels and the number of follicles greater than or equal to 16 mm when all 32 cycles were combined (r = 0.40). It is suggested that pulsatile HMG and FSH in combination with clomiphene are in general equally effective in inducing multiple follicular development in normal women. However, individual responses show great variability. PMID- 3104398 TI - Autoimmunity, fetal losses, lupus anticoagulant: beginning of systemic lupus erythematosus or new autoimmune entity with gynaeco-obstetrical expression? AB - Among the various autoantibodies commonly found in women with systemic lupus erythematosus, the so-called lupus anticoagulant has been described in association with fetal losses. Recently, women with repeated spontaneous abortions and lupus anticoagulant, but no apparent systemic lupus erythematosus have been described. We have studied prospectively the possible connections between fetal losses and autoimmunity in a large control study of 130 idiopathic habitual aborters. These non-pregnant patients without any antecedent autoimmune disease were explored for the presence for autoantibodies especially lupus anticoagulant. Ten percent of the patients exhibit an antithromboplastin antibody (lupus anticoagulant) and half of this group possesses a striking association of biological manifestations of autoimmunity. In conclusion, two points appear: firstly, statistical correlation is demonstrated between antithromboplastin antibody and habitual abortion; secondly, doubt remains about the significance of the association between autoimmunity, fetal losses and antithromboplastin: beginning of systemic lupus erythematosus or new autoimmune entity with gynaeco obstetrical expression. PMID- 3104399 TI - Arachidonic acid metabolism in human granulosa cells: evidence for cyclooxygenase and lipoxygenase activity in vitro. AB - In view of the studies demonstrating the involvement of eicosanoids (prostaglandins and hydroxyperoxides, including leukotrienes) in ovulation in several mammalian species, we have examined the activity of the two enzyme systems, lipoxygenase and cyclooxygenase in human granulosa cells obtained from women undergoing in-vitro fertilization--embryo transfer. The activity of cyclooxygenase was assessed by radioimmunoassay of prostaglandin E and of 6-keto prostaglandin F1 alpha, the conversion product of prostacyclin, accumulated in the culture medium of granulosa cells. Lipoxygenase activity was detected by the conversion of [14C]arachidonic acid into its products (hydroxyperoxides and leukotrienes) separated by reversed phase high-performance liquid chromatography. The results confirmed the activity of cyclooxygenase in human granulosa cells, production in vitro of prostaglandin E and prostacyclin and demonstrated the presence of active lipoxygenase enzymes. These results support the possible involvement of eicosanoids in ovulation of the human. PMID- 3104400 TI - Management of gonadotrophin-induced cycles characterized by a significant discrepancy between oestrogen levels and dominant follicle size. AB - The incongruity between oestrogen elevation and immature follicles is one of the problems encountered during the induction of ovulation with gonadotrophins. This phenomenon is particularly pertinent in women with polycystic ovarian disease. Our work presents a regimen of treatment that was found helpful in overcoming this problem. It is based on a close ultrasonic assessment of the follicular growth, which also serves as the sole means for the decision of human chorionic gonadotrophin (HCG) administration (mature follicle range is 19-25 mm). Accordingly, the human menopausal gonadotrophin doses were individually adjusted and, if necessary, omitted in an effort to avoid excessive oestrogen elevation at the time of HCG administration. The resultant plateau or decline of oestrogen levels in our series do not interfere with ovulation. Seventeen conceptions occurred after 53 treatment cycles in 19 women. PMID- 3104401 TI - Clinical evaluation of drugs used in fertility regulation. AB - The clinical evaluation of drugs used in fertility regulation is initially assessed in Phase I, II and III trials. The design of each phase and the investigative staff must be adequate. In Phase I, normal, healthy human volunteers meeting specific guidelines are usually studied. Numbers vary between 20 and 80 and the purpose is to determine the acute toxicity of the compound. In Phase II, efficacy and safety are examined in a clinical target population, and emphasis may be placed on pharmacological and mechanistic studies. Usually between 50 and 200 patients are involved. In Phase III, large-scale clinical studies for local registration and the introduction of drugs to various countries are included. This paper describes the evaluation of various drugs used in contraception, including NORPLANT implants, and considers the efficiency, safety and acceptability of such drugs. Phase IV studies are usually needed to reveal chronic toxicities or rare events. PMID- 3104402 TI - T cell line-mediated EAE: prevention and therapy by a monoclonal antibody specific for T lymphoblasts. AB - We studied the effect of a novel monoclonal antibody, pta-3, on T cell line mediated experimental allergic encephalomyelitis (EAE). The antibody is specific for a differentiation antigen expressed by activated rat T lymphocytes and is cytotoxic in the presence of rat complement for a minor subpopulation of leukocytes, including encephalitogenic T cells (Schluesener et al. 1986). Single intraperitoneal injections of antibody effectively prevented or abrogated lethal EAE. Therapeutic effect was dependent on time of treatment, but even established disease could be cured. Due to the specificity of the antibody for the disease inducing lymphocytes, no side effects of treatment could be observed in living animals or by autopsy. PMID- 3104403 TI - Role of local immunosuppression in murine fetoplacental listeriosis. AB - Recent evidence suggests that local immunoregulation may prevent rejection of the placenta by the mother. This local immunoregulation may also compromise the response to placental infection. Listeria monocytogenes infection in 121 pregnant mice and 1,050 fetoplacental units was examined and the kinetics of bacterial growth in various maternal and fetal tissues were determined. A subset of pregnant mice developed overwhelming placental listeria infections. Pregnancy did not impair the maternal immune response in the liver and spleen. Pregnant mice without placental infection had numbers of listeria equivalent to nonpregnant controls and mice immunized during pregnancy had significantly less listeria than nonimmunized controls. The secondary response in immunized pregnant mice had no effect on the development of placental infection and the histologic features of placental infection were distinct from those in other organs. Our data suggest that an ineffective local immune response may contribute to the pathogenicity of listeria for the placenta. PMID- 3104404 TI - Gamma-interferon inhibits collagen synthesis in vivo in the mouse. AB - Subcutaneous implantation of osmotic pumps into CAF1 mice resulted in the formation of thick fibrous capsules around the pumps. When pumps were loaded with recombinant murine gamma-interferon (rMuIFN-gamma) to deliver 2 X 10(3) U/h for 14 d, there was a marked decrease in thickness and collagen content of the capsules from rMuIFN-gamma-treated animals compared with capsules from animals receiving diluent alone. The collagen content of the capsules was estimated by hydroxyproline analysis of the tissue and by quantitative electron microscopy of collagen bundles. Heat-inactivated rMuIFN-gamma failed to reduce the fibrotic response in this assay. These results provide compelling evidence that gamma interferon can down-regulate collagen synthesis in vivo and suggest the possibility that this lymphokine may be useful in the treatment of disease states characterized by excessive fibrosis. PMID- 3104405 TI - Pulmonary carbon dioxide and panic-arousing sensations after 35% carbon dioxide inhalation: hypercapnia/hyperoxia versus hypercapnia/normoxia. AB - Experimental research has demonstrated that CO2 inhalation provides a valid laboratory model for acute panic. Earlier studies employed CO2/O2 mixtures that were not only hypercapnic but also hyperoxic, raising the question of the relative contribution of the hyperoxidity. A comparison between a hypercapnic/hyperoxic mixture (35% CO2/65% O2) and a hypercapnic/normoxic mixture (35% CO2/20% O2/45% N2) revealed no differences on self-reported panic symptoms or end tidal pCO2. It is concluded that findings from previous CO2/O2 inhalation studies should be attributed to the hypercapnic, rather than to the hyperoxic, nature of the mixtures. PMID- 3104406 TI - Factor VIII related antigen positive macrophages and acquired immune deficiency syndrome (AIDS): a problem of antibody specificity. AB - A further histopathological complication of atypical mycobacterial infection in acquired immune deficiency syndrome (AIDS) is reported. Positive reactivity between mycobacterial antibodies within a polyclonal antiserum and mycobacteria within tissues resulted in false positivity with this reagent to factor VIII related antigen. This complication may be avoided either by prior testing of the antiserum, or by purification, or by the use of monoclonal antibodies. Histopathologists examining tissues from patients with AIDS and those with disseminated mycobacterial infections and using immunohistochemical techniques should be aware of this occurrence. PMID- 3104407 TI - Enzyme histochemistry on jejunal tissue embedded in resin. PMID- 3104408 TI - Experimental ovine sarcocystosis: sequential ultrastructural pathology in skeletal muscle. AB - Six lambs inoculated with 70,000 Sarcocystis oocysts were killed at 14, 25, 33, 42, 60 and 81 days post-inoculation (pi). Tissue changes and developing cysts in one muscle (left M. semimembranosus) were studied by transmission electron microscopy. Perivascular macrophages contained intracytoplasmic merozoites at 25 and 33 days pi. Cysts with metrocytes were established at 42 days pi, at which time cyst wall zones were simple without surface projections. At 60 days pi, cysts contained metrocytes, some in division, and immature cystozoites. Cylindrical cyst surface projections were 1.55 microgram tall, 0.45 microgram wide and had specialized tip and base zones. Cysts at 81 days pi contained metrocytes and mature cystozoites. Cyst surface projections had a regular association with mitochondria of the parasitized myocyte. A mild or moderate myositis developed during both meront (25 to 33 days pi) and cyst-forming (42 to 81 days pi) stages. Initially histiocytic, the exudate eventually consisted of plasma cells and macrophages. A small minority of parasitized myocytes attracted a local inflammatory reaction. Following macrophage invasion of the sarcoplasm, the cyst wall zone degenerated and underwent phagocytosis and cystozoites became pyknotic. With advanced cyst degeneration there was local destruction of the host muscle fibre. PMID- 3104409 TI - Careers in dentistry: a successful blending of practice and home. PMID- 3104410 TI - Dentistry: my personal goal. PMID- 3104412 TI - Academic/clinical career: the best of both worlds. PMID- 3104411 TI - Women in academic dentistry: the fight/flight dilemma. PMID- 3104413 TI - Caring for the community: dentistry at the Community Health Services in Hartford. PMID- 3104414 TI - Dental treatment of a patient with severe attrition of anterior teeth. PMID- 3104415 TI - HMO's incentives: a prescription for failure. PMID- 3104416 TI - The importance of understanding risk management and its potential impact on the professional liability crisis. PMID- 3104417 TI - Gardening: a relaxing rewarding hobby. PMID- 3104418 TI - The woman--1986. PMID- 3104419 TI - The affective domain--equal opportunity in nursing education? PMID- 3104420 TI - Continuing education approval program: interrater reliability. PMID- 3104421 TI - An innovative strategy to facilitate nurse-physician interaction. PMID- 3104422 TI - Integrating a critical care internship with a career ladder. PMID- 3104423 TI - Expanding the concept of continuing education conferences: the conference participants as a Delphi method sample. PMID- 3104424 TI - Effecting change in a community hospital: implications for staff development. PMID- 3104425 TI - A hospital-wide AIDS education program. PMID- 3104426 TI - Annual reports--amulets for administrators. PMID- 3104427 TI - Parakeratotic horns in a patient with myeloma. AB - We describe a patient who in association with myeloma developed generalized keratotic horns. Light microscopy revealed parakeratotic plugs resembling those seen in Kyrle's disease. Electron microscopy showed distortion of keratinosomes and laminated bodies indicating a profound disturbance in keratinization. A strong C3 and weaker IgG and IgA immunofluorescence were seen in the areas of epidermal plugs and horns but no circulating epidermal antibodies were detected. All symptoms disappeared when therapy for myeloma was started favoring that they were of paraneoplastic origin. PMID- 3104428 TI - Feeding gastrostomy. Part I. Indications and complications. PMID- 3104429 TI - Diabetic emergencies and the Loch Ness monster. PMID- 3104430 TI - Prolonged extracorporeal CO2-removal in severe adult respiratory distress syndrome. Neuropathological observations in two cases. AB - Extracorporeal CO2-removal (EC-CO2-R) using a membrane lung system was applied for 12 and 20 days respectively in two young men with adult respiratory distress syndrome (ARDS). Neuropathological examination revealed only moderate hypoxic changes of unusual distribution. In the first case nerve cell loss in Sommer's sector of the hippocampus and focal incomplete necroses in both putamina were interpreted as the result of cardiac arrest at the onset of the disease rather than of chronic hypoxia. Findings in the second case were confined to nerve cell necroses of a minor degree in the cerebral cortex. Remarkably, the cerebellum was spared in both cases. Our observations suggest that EC-CO2-R was not associated with neuropathological findings which could be attributed specifically to this procedure. PMID- 3104431 TI - Fluid resuscitation in diabetic emergencies--a reappraisal. AB - The first objective in diabetic ketoacidosis is to restore the circulating volume and improve tissue perfusion. In any form of hypovolaemic shock the most efficient way of restoring circulating volume is to be use colloid solutions rather than crystalloids. At least three times the amount of crystalloid must be used to achieve the same effect. The historical reason for using isotonic saline in diabetic ketoacidosis is related not to its similarity to the fluid lost, but to its supposed efficiency in correcting the circulating volume. Excess crystalloid expands the interstitial space which results in pulmonary oedema, peripheral oedema and possibly cerebral oedema. Although currently difficult to define precisely in their more subtle forms, they all produce adverse pathophysiological effects. The fluid loss in diabetic ketoacidosis is equivalent to "half-normal" saline, a relatively hypotonic solution. As well as causing extensive oedema, resuscitation with isotonic saline can increase serum sodium and osmolarity while not providing free water to replace the intracellular losses. PMID- 3104432 TI - Total parenteral nutrition in critically ill surgical patients: fixed vs tailored caloric replacement. AB - In critically ill patients accurate measurement of total energy expenditure (TEE) is possible by means of continuous indirect calorimetry. Since in many ICUs the necessary equipment is not available, the Harris-Benedict formula (HB) is frequently used to calculate TEE. Supplemental application of a clinical correction factor (HBc) has been advised. In this study we assessed the reliability of both methods of calculation and of a standard nutritional regimen, all three compared to the calorimetrically measured TEE (gold standard). Although the basic HB-formula did not perform better than the standard regimen, significantly better results were obtained by supplemental application of the clinical correction factor (HBc). It is left undecided, whether or not indirect calorimetry is actually to be preferred in daily clinical practice. PMID- 3104434 TI - Effects of lithium carbonate on the memory and motor speed of bipolar outpatients. PMID- 3104433 TI - Influence of nimodipine and nifedipine on intrapulmonary shunting--a comparison to other vasoactive drugs. AB - This study was assigned to investigate the influence of calcium channel blockers (nimodipine and nifedipine) in comparison to other vasoactive drugs (nitroglycerin, dopamine) on pulmonary shunting (Qs/Qt). Fifty anesthetised patients scheduled for aortocoronary bypass operation were randomly allocated to 5 groups receiving one of the following drugs: nimodipine 1.0 microgram X kg-1 X min-1; nifedipine 0.7 microgram X kg-1 X min-1; nitroglycerin (TNG) 0.5 microgram X kg-1 X min-1; dopamine; micrograms X kg-1 X min-1; placebo (0.9% NaCl). Nimodipine as well as nifedipine led to a significant increase in cardiac output (+44%; +39%), pulmonary vascular resistance simultaneously decreased (-25%; 28%). PaO2 increased significantly (+16%; +13%), too, whereas Qs/Qt remained almost unchanged. In contrast, the increase in cardiac output induced by dopamine (+27%) was accompanied by a significant increase in shunting (+34%). TNG application did not alter Qs/Qt, but pulmonary artery pressure (PAP) decreased markedly (-19%). PMID- 3104435 TI - Early tolerance to hemodynamic effects of high dose transdermal nitroglycerin in responders with severe chronic heart failure. AB - Transdermal systems for delivery of nitroglycerin have been shown to provide sustained blood levels of the drug for at least 24 hours. Investigations of hemodynamic effects of transdermal nitroglycerin in patients with heart failure have demonstrated a transient reduction in pressure lasting less than the expected 24 hours. These findings could be due to the development of circulatory tolerance to the vasodilatory effects of nitroglycerin or to insufficient drug dosing. In the present study, we compared the hemodynamic effects of the first and the second doses of high dose (120 mg) transdermal nitroglycerin given 24 hours apart in 11 responders (greater than or equal to 20% reduction in mean pulmonary artery wedge pressure lasting greater than or equal to 2 hours). Initiation of nitroglycerin therapy resulted in a significant reduction in mean right atrial pressure lasting for 14 hours and in a reduction in mean pulmonary artery and mean pulmonary artery wedge pressures lasting 24 hours. After administration of the second dose, mean right atrial pressure at 2 hours (9 +/- 5 versus 7 +/- 4 mm Hg), 4 hours (8 +/- 5 versus 6 +/- 4 mm Hg) and 8 hours (8 +/- 5 versus 6 +/- 3 mm Hg) was higher than after the first dose (p less than 0.05). Both mean pulmonary artery and mean pulmonary artery wedge pressures were significantly higher after the second nitroglycerin dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104436 TI - A computer-based Markov decision analysis of the management of symptomatic bifascicular block: the threshold probability for pacing. AB - This review illustrates the use of computer-based Markov models to estimate cost effectiveness and prognosis in a complex problem in clinical cardiology. Decision analysis and cost-effectiveness analysis were used to assess whether to implant a permanent cardiac pacemaker, treat with drugs, perform electrophysiologic studies or observe patients who have two clinical features--syncope and bifascicular block--that may or may not be causally related. Using a Markov process model, a computer program simulated the prognosis of five cohorts of such patients--one treated conservatively, one given empiric antiarrhythmic drug therapy, one receiving a pacemaker, one treated with empiric drugs and pacing and one tested with electrophysiologic studies. On the basis of data from published reports and expert opinion, quality-adjusted life expectancy was calculated by summing the average time a member of each cohort would survive with and without symptoms for each initial treatment choice. The costs were estimated from 1985 hospital charges. For patients with normal left ventricular function, electrophysiologic testing provides a benefit of 14 quality-adjusted months of life over observation, at an additional cost of $24,200. Empiric pacing would add 2.5 additional months, at a further cost of $14,300. In patients with poor left ventricular function, empiric drug therapy offers 1.5 additional quality-adjusted months over observation, at a cost of $6,900. Electrophysiologic testing provides a further 16.5 months at an additional cost of $16,900. These results hold when the relation between symptoms and arrhythmia is not firmly established. Varying the probabilities of underlying ventricular tachyarrhythmias, bradyarrhythmic conduction defects or noncardiac causes of syncope affects the cost-effectiveness relative to the alternative treatments. PMID- 3104437 TI - Nutrition support of the adult liver transplant candidate. AB - Liver transplantation now provides a viable alternative to patients with end stage hepatic failure. Because of the damaging effects of liver failure on other organ systems, transplant candidates frequently suffer from moderate to severe malnutrition. Chronic hepatic failure can result in deranged metabolism of not only macronutrients and micronutrients but also various hormones. Patients are frequently in a catabolic state. Wasting of the skeletal muscle mass occurs and synthesis of secretory proteins and clotting factors decreases. Hepatic encephalopathy and fluid/electrolyte imbalances often complicate the provision of appropriate nutrition support. Nutrition support may be provided by the oral route, tube feeding, parenteral nutrition, or a combination of those routes. A multidisciplinary approach to determine the appropriate nutrition support regimen is most optimal. To assess the efficacy of the support, monitoring of the nutritional/metabolic status is necessary on an ongoing basis. An aggressive nutrition support regimen can induce positive nitrogen balance, promote hepatic protein synthesis, and expand lean body mass, controlling the symptoms of malnutrition in end-stage liver disease. PMID- 3104438 TI - Regulation of thyrotropin secretion in nonthyroidal illness. PMID- 3104439 TI - Thyroxine kinetics in nonthyroidal illnesses. AB - Free T4 estimates by equilibrium dialysis appear to reflect serum free T4 levels in vivo in patients with nonthyroidal illnesses. However, patients with either elevated or modestly reduced free T4 values appear to be clinically euthyroid and have relatively normal free T4 availability to tissues as judged by the normal production rates of reverse T3 from T4, and by the minimally altered TSH status. Thus, increased or modestly reduced serum free T4 levels by equilibrium dialysis in patients with nonthyroidal illnesses do not appear to indicate the presence of overt T4 excess or deficiency, respectively, and, therefore, the clinician should strive to avoid unnecessary and potentially harmful therapy in these patients. Conversely, concurrent thyroid gland disease may be present which must be accurately diagnosed and treated to alleviate the morbidity induced by hyperthyroidism or hypothyroidism in sick patients. PMID- 3104440 TI - Drug induced changes in thyroid function parameters. PMID- 3104441 TI - The value of sensitive TSH measurements in clinical practice. PMID- 3104442 TI - Effects of hyperthermia on fetal breathing movements. AB - High environmental temperature is known to impair fetal growth and development. We now report long lasting changes in fetal breathing activity following the exposure of pregnant ewes to an ambient temperature of 43 degrees C for 8 h. In 16 trials in 10 ewes (119-138 days gestation) heat exposure increased maternal and fetal core temperatures 1.5-2.0 degrees C, and the hyperventilation by the ewe produced a fall in fetal PaCO2 from 53.5 +/- 1.3 to 34.8 +/- 5.3 mmHg (P less than 0.05). Fetal breathing movements decreased in incidence during the hyperthermia but remained episodic (present during low-voltage electrocortical activity) with occasional brief episodes of breathing at high rates (greater than 4 breaths/s). However, 1-2 h after the end of heating, when maternal and fetal core temperature and PaCO2 had returned to normal, fetal breathing movements became continuous, and were augmented 30-100% in amplitude. Fetal breathing movements occurred during both low- and high-voltage electrocortical activity. The results show that a heat load similar to that experienced by sheep in sub tropical regions in the summer months cause prolonged changes in the central regulation of fetal breathing. PMID- 3104443 TI - Ventilatory and metabolic responses to acute hypoxia in infants assessed by transcutaneous gas monitoring. AB - Transcutaneous PO2, transcutaneous PCO2 and respiratory pattern were monitored during acute mild hypoxia (15% O2) in quiet sleep. Eighteen healthy infants were studied sequentially at 1-5 days, 4-8 weeks and 10-14 weeks of age. The transcutaneous PCO2 changes (delta PCO2) related to the transcutaneous PO2 fall, were used as an index of the total ventilatory and metabolic response during the test. This calculated index was related to the occurrence of arousal and periodic breathing. Transcutaneous PCO2 increased above control levels in infants 1-5 days old, decreased markedly in infants 4-8 weeks of age, and decreased slightly or remained unchanged in the 10-14 weeks old infants. The changes in response pattern were significant (P less than 0.006). These differences in response were not reflected in the lowest values of transcutaneous PO2 attained during the test. The lowest transcutaneous PO2 levels did not differ significantly between the age groups, indicating that the mechanisms maintaining PO2 during hypoxia may change during development. Periodic breathing was always associated with a decrease in transcutaneous PCO2 and in 8 out of 10 tests where it occurred it commenced at the lowest transcutaneous PCO2 level recorded. These results do not support the concept that periodic breathing is a sign of hypoventilation. Arousal was observed in less than half of the infants and was not related to the degree of hypoxaemia. We conclude that hypoxic arousal in infants may not be the important escape mechanism as suggested previously. PMID- 3104444 TI - Aspiration after percutaneous gastrostomy. Assessment by Tc-99m labeling of the enteral feed. AB - Aspiration pneumonia, a recognized complication of enteral feeding via a nasogastric tube, is considered uncommon with percutaneously placed gastrostomy tube feeding. We report aspiration pneumonia during enteral alimentation in a neurologically compromised but conscious patient. Aspiration continued despite changing the route of enteral feeding from nasogastric to percutaneous gastrostomy. Quantitative scintigraphic studies with Tc-99m-labeled enteral infusion demonstrated frequent episodes of gastroesophageal reflux and aspiration of gastric contents, which increased when the infusion rate was speeded up for nutritional replacement. Gastric retention also occurred at the higher infusion rate. Thus, percutaneous gastrostomy may not decrease the frequency of aspiration in patients at risk. PMID- 3104445 TI - Influence of HBV replication and delta agent superinfection on T cell subsets and killer (Leu 7+) in chronic hepatitis B virus infection. AB - Peripheral blood T-lymphocyte subsets and cells reacting for Leu 7 antigen, which identifies a subset of killer and natural killer cells, have been examined in 32 patients chronically infected by the hepatitis B or D viruses (HBV, HDV) and in 28 normal subjects. The T8+ lymphocytes were increased and the T4/T8 ratio was decreased in patients with HBV replication (identified by the presence of HBcAg in liver and HBV-DNA in serum) and in patients with HDV infection (HDAg in liver). These patients had more active liver disease than patients without evidence of viral replication, B or D, who showed normal lymphocyte counts. Leu 7+ lymphocytes were also increased in patients with viral replication and active disease and correlated positively with alaninaminotransferase serum levels. These observations suggest the participation of both T8+ and Leu7+ cells in the pathogenesis of liver cell injury in HBsAg-positive chronic liver disease. PMID- 3104446 TI - Fluvoxamine in the treatment of the older depressed patient; double-blind, placebo-controlled data. AB - Fluvoxamine was given in placebo-controlled trials to 33 severely depressed patients of between 60 and 71 years, 29 received imipramine and 14 placebo. At week 4 of treatment fluvoxamine and imipramine were superior to placebo on the HAMD and CGI scales (P less than 0.05). There was indication of an earlier onset of antidepressant activity in the fluvoxamine group. There was no evidence of systematic changes in laboratory variables in any treatment group. Fluvoxamine and placebo had similar effects on heart rate and blood pressure. Imipramine was associated with significant postural falls in mean systolic pressure. The most frequent unwanted symptom with fluvoxamine was mild nausea, with imipramine, dry mouth. Toxic confusion was the major reason for dropout in the imipramine (n = 4) and nausea (n = 3) in the fluvoxamine-treated group. PMID- 3104448 TI - Single dose pharmacokinetics of 5 formulations of lithium: a controlled comparison in healthy subjects. AB - The single dose pharmacokinetics of 4 lithium preparations (Camcolit-400, Priadel, Liskonum, Litarex) and a new micro-encapsulated formulation were compared in normal volunteers using a balanced cross-over design. The data show an inverse relationship between rate of release and bioavailability. The pharmacokinetic characteristics of Camcolit-400 and Priadel were similar; both showed earlier and greater peak serum concentrations than the other 3. The new formulation, which accounted for most of the significant variance, had the slowest rate of release and the lowest bioavailability. Statistical analysis showed significant differences between the 5 preparations for C-max, T-max, 12-h serum levels, AUC and urinary excretion, but not for the 24-h serum levels. No serious untoward side-effects were noted. PMID- 3104447 TI - Prediction of the amitriptyline response: psychopathology versus neuroendocrinology. AB - In this prediction study 50 patients with DSM-III major depressive episode were assessed before treatment with respect to symptomatology (Newcastle and Hamilton features), diagnostic sub-types (according to the Newcastle scale and the DSM III) and neuroendocrinology (DST and TRH-test). Subjects were given 150 mg of amitriptyline daily and the treatment response was determined on day 11 and 21. The duration of hospitalization served as a further criterion of outcome. The data suggest that neither diagnostic sub-typing nor neuroendocrinological variables were significantly related to outcome. Prediction, however, became possible using the following clinical parameters: DSM-III depressive psychotic features, DSM-III personality disorder and sudden onset of illness were significantly associated with poor treatment response and explained 34% of the outcome variance. PMID- 3104449 TI - Chicken developmental antigens in 15I5-B-congenic lines. AB - Six partially developed 15I5-B-congenic lines of chickens were used to assess the genetic influence on the developmental expression of selected epitopes of two avian developmental antigen systems: chicken fetal antigen (CFA) and chicken adult antigen (CAA). Both CFA and CAA are serologically and molecularly complex hematopoietic antigen systems, yet little is known about genetic influences on their expression. Using polyclonal rabbit anti-CFA, only slight variations in overall CFA expression on peripheral erythrocytes were observed during neonatal development; no consistent trend was evident. In contrast, analysis with monoclonal antibody 10C6 revealed that the incidence of CFA determinant 8 (CFA8) on erythrocytes of the early neonate was significantly reduced in line 15I5 compared with lines .6-2, .7-2 and .15I-5; line .C-12 also exhibited a reduced CFA8 incidence at hatching. Likewise, the CAA epitope detected by monoclonal antibody 3F12 was found to appear at a slower rate on erythrocytes from lines 15I5 and .C-12 than on those of other lines. Similar results were obtained using the anti-CAA monoclonal 4C2 where reduced expression was found in lines 15I5, .C 12, and .P-13. Results of complement-mediated cytolysis using the positive control 9F9 monoclonal antibody suggested that observed genetic differences were not due to inherent differences in erythroid cytolytic sensitivity. Neither could the results be explained by the incidence of circulating reticulocytes vs. mature erythrocytes within the lines. Rather, the results suggest that different genetic lines of chickens vary in the developmental kinetics of definitive erythrocyte subpopulations bearing specific phenotypes defined by monoclonal antibodies. These findings are discussed in light of previous observations using these B congenic lines. PMID- 3104450 TI - Detection of mRNAs present at low concentrations in rat liver by in situ hybridization: application to the study of metabolic regulation and azo dye hepatocarcinogenesis. AB - In situ hybridization on tissue sections was used to detect mRNAs present at low concentrations during metabolic adaptation and azo dye carcinogenesis in rat liver. The method consisted of hybridizing the slices at relatively high stringency with [35S]-labeled single-stranded probes derived from cDNA insert clones into the M13 phage. L-pyruvate kinase mRNA was proved to be present at very low concentrations in hepatocytes of fasted rats and to be relatively abundant in all hepatocytes after 18 hr of refeeding on a carbohydrate-rich diet. Aldolase A mRNA concentrations have been previously shown to increase markedly in liver of 3'-methyl DAB-fed rats, with a maximum at the fourth week. We demonstrate here, using our in situ hybridization technique, that this phenomenon is not due to re-expression of this "fetal marker" in hepatocytes but to its abundancy in proliferating small cells (i.e., so-called oval and transitional cells). Small amounts were also detected in sinusoidal cells. In normal liver, aldolase A mRNAs were detected only in some sinusoidal cells. PMID- 3104451 TI - IL 1 expression in a clone of human T cells. AB - Three human T cell clones, all of which are T3+, T4+, T8-, and T11+, were examined for IL 1 production. Two clones were found to express readily detectable, membrane-bound IL 1 activity upon stimulation with OKT3 antibody, rIL 2, and PMA. Northern blot analysis of RNA from one of the clones shows that cells can be induced to express the genes for both IL 1 alpha and IL 1 beta. Furthermore, the pattern of expression in response to different stimuli suggests that the genes for IL 1 alpha and IL 1 beta are regulated independently. PMID- 3104452 TI - Role of CD2 and IL 1 beta in T cell responsiveness to IL 2. AB - We have evaluated the effects of an anti-CD2 monoclonal antibody (moAb), Leu-5b, on inhibition of lymphocyte responsiveness. Given previous reports that anti-CD2 moAb prevent production of interleukin 2 (IL 2), as well as up-regulation of IL 2 receptor, we chose a test system in which lymphocytes were activated by exogenously added recombinant IL 2 (rIL 2). Our studies thus allowed us to evaluate other possible mechanisms by which anti-CD2 moAb could act. We found that Leu-5b not only blocked the proliferative response of human peripheral blood leukocytes (PBL) to IL 2, but also the development of cytotoxicity as assayed in lectin-dependent cytotoxicity (LDCC). Addition of recombinant interleukin 1 beta (rIL 1 beta) reconstituted the proliferative response in the presence of Leu-5b but did not allow development of cytotoxicity. Our findings are consistent with the concept that Leu-5b delivers a signal to IL 2-responsive cells that prevents their subsequent proliferation and development of cytotoxicity, but that only the former event, i.e., proliferation, is reconstituted by the addition of IL 1 beta. PMID- 3104453 TI - Characterization of an immunosuppressive factor derived from colon cancer cells. AB - The colon cancer cell line, HT29, produces a soluble substance (HT29 factor) that blocks mitogen-induced T cell proliferation and the production of interleukin 2 (IL 2). Inhibition of T cell proliferation by the HT29 factor is reversible and is not due to a decline in cell viability or an alteration in the kinetics of T cell proliferation. It occurs even when the HT29 factor is added only 24 hr before terminating the T cell cultures, indicating that the factor affects cell division after activation of T cells has already occurred. No inhibitory activity was found in medium conditioned by human colonic epithelial cells or fibroblasts. The factor has an apparent m.w. of 56,000 and an isoelectric point of 7.9. It is sensitive to endopeptidases, heating to 56 degrees C, and extremes of pH. The HT29 factor also suppresses IL 2 production by T cells. However, low IL 2 availability alone cannot account for the suppressive effect of the factor on T cell proliferation, because the addition of exogenous IL 2 does not reverse the inhibition. This block in IL 2 responsiveness is not primarily due to a decrease in IL 2 receptors because Tac expression on activated T cells is minimally decreased during a 24-hr exposure to the HT29 factor. In addition, IL 2-induced proliferation of mitogen-activated T cells is inhibited only slightly by the HT29 factor, indicating that a block in the interaction of IL 2 with its receptor is not its main mechanism of action. Thus the inhibition of T cell proliferation is likely to be due primarily to a mechanism independent of IL 2. PMID- 3104454 TI - Ligand-receptor interactions required for commitment to the activation of the interleukin 2 gene. AB - Concanavalin A (Con A), which together with phorbol myristate acetate (PMA) can activate the human T cell line Jurkat to produce interleukin 2 (IL 2), is shown to depend on the expression of the T3/T cell antigen receptor heterodimer (T3/Ti) complex to induce activation. alpha-methyl mannoside was able to reverse all of the observed effects of Con A on intracellular biochemical events. Therefore, ligand-receptor occupancy appears to be required for sustaining biochemical events associated with triggering the T3/Ti complex. Studies of the time dependent requirements for the two stimuli required for activation revealed that simultaneous stimulation with both Con A and PMA is required for 2 to 4 hr for the cell to commit itself to activation, as measured by the appearance of secreted IL 2. This 2- to 4-hr requirement correlated precisely with the appearance of IL 2 mRNA, and the appearance of IL 2 transcripts depended on protein synthesis during this critical time period. PMID- 3104455 TI - Intracellular growth of Listeria monocytogenes as a prerequisite for in vivo induction of T cell-mediated immunity. AB - The in vivo induction of T cell-mediated immunity was studied by infecting mice with two genetically closely related mutants from Listeria monocytogenes, differing only with respect to the secretion of an active SH-dependent hemolysin. It is shown that even minute doses of hemolytic bacteria capable of growing in host tissues easily induced the expression of T cell-mediated immunity, as estimated by the level of delayed sensitivity, adoptive protection and long lasting immunological memory. On the contrary, nonhemolytic bacteria unable to multiply in host tissues totally failed to initiate the expression of T cell mediated immunity in vivo. This failure was even observed when mice were repeatedly infected by high doses of nonhemolytic bacteria, allowing to maintain a significant amount of viable bacteria for several days in host tissues. These results mean that the presence of viable bacteria at a significant level in the host is not sufficient per se to induce detectable T cell clonal expansion in the in vivo setting, implying that the process of bacterial growth inside macrophages is required to initiate in vivo the expression of T cell-mediated immunity. PMID- 3104456 TI - Experimental visceral leishmaniasis: production of interleukin 2 and interferon gamma, tissue immune reaction, and response to treatment with interleukin 2 and interferon-gamma. AB - During the first 2 to 4 weeks of progressive visceral infection with the intracellular protozoan, Leishmania donovani, spleen cells from BALB/c mice failed in response to leishmanial antigen to produce either of the activating T cell-derived lymphokines, interleukin 2 (IL 2) or gamma-interferon (IFN-gamma). Four weeks after infection, however, antigen-induced IL 2 and IFN-gamma secretion emerged and coincided with the onset of control over parasite replication and the subsequent killing of greater than 80% of intrahepatic L. donovani. The development of this immunosecretory activity correlated with the hepatic tissue response at the site of parasitized Kupffer cells. This response progressed from Kupffer cell fusion (week 1) to fusion plus a mononuclear cell infiltrate (week 2) to well-organized granuloma formation (weeks 4 to 8). In contrast, T cell deficient nude BALB/c mice exerted no control over L. donovani, their spleen cells failed to generate antigen-induced IFN-gamma, and at 4 weeks, their livers were devoid of any tissue reaction. Since spleen cells from 2-week infected normal mice did not produce antigen-stimulated IL 2 or IFN-gamma, these mice were treated with recombinant (r) lymphokines. Various protocols using both high and low dose human rIL 2 had no antileishmanial effect. Hepatic parasite replication was completely halted, however, by macrophage-activating doses of murine rIFN gamma. These results reemphasize that an intact T cell-dependent response is required for successful defense against L. donovani, indicate that this immune response can be measured at both the cellular (secretory) and tissue levels, and confirm that IFN-gamma can exert an antileishmanial effect in vivo. PMID- 3104457 TI - Start of mu-chain production by the further two-step rearrangements of immunoglobulin heavy chain genes on one chromosome from a DJH/DJH configuration in an Abelson virus-transformed cell line: evidence of secondary DJH complex formation. AB - A variant was selected from an Abelson virus-transformed cell line with identifiable and distinguishable DJH rearrangements on both chromosomes. Southern blotting experiments suggested that this variant resulted from a secondary DJH complex formation accompanied with the deletion of one of the DJH rearrangements on the same chromosome. Furthermore, this variant started making mu-chains by the further functional join of a VH gene to the secondarily formed DJH complex. Thus, we describe here the first evidence of a secondary DJH complex formation. PMID- 3104458 TI - A new cross-reactive idiotype-defined family in the phthalate humoral immune response of mice. I. Linkage of VH-Xmp to IgCH allotype locus and mapping with respect to other known VH genes. AB - A cross-reactive idiotype family was previously identified from a very large library of phthalate-specific hybridoma clones. The prototype of this idiotype family is the hybridoma, 2E9, secreting an IgM antibody with phthalate specificity. A portion of both primary and secondary anti-phthalate antibodies elicited in all BALB/c mice tested expresses the 2E9 cross-reactive idiotype. This idiotype has now been found in the anti-phthalate antibodies of several other inbred strains of mice (A/HeHa, DBA/2, and C3Hf/HeHa) tested but not in C57BL/6 mice. Anti-phthalate antibodies elicited from congenic mice BC.8, which express the same IgCH allotype as BALB/c mice but possess C57BL/6 genetic background, contain the 2E9 cross-reactive idiotype, whereas this idiotype is not expressed on the anti-phthalate antibodies derived from another congenic mouse CB.20, which expresses a C57BL/6 IgCH allotype and a genetic background of the BALB/c strain. These results indicate that the gene controlling the 2E9 idiotype is closely linked to the IgCH allotype locus. The 2E9 cross-reactive idiotype was also found in all of the F1 mice (BALB/c X C57BL/6) tested, and the level of expression of this idiotype in the F1 mice was quantitatively equivalent to the allotype/idiotype homozygous mice. The expression of the 2E9 idiotype in the phthalate repertoire has been followed in 12 different wild mouse populations. As expected, the 2E9 idiotype was observed in a large proportion of the wild mouse strains. Surprisingly, several examples of nonconcordance in the expression of idiotype and allotype were observed in these mice. One likely explanation for the linkage breakdown is a crossing over of the heavy chain constant and variable region gene complexes. In the SM/J inbred strain of mice, where such a crossover has occurred, nonconcordance between allotype and 2E9 idiotype expression was demonstrated. By using the recombinant inbred BXD strains of mice, the VH gene encoding the 2E9 idiotype has been mapped with respect to other known VH gene families. Relative to other VH genes the VH-Xmp is situated very close to the IgCH gene region. PMID- 3104459 TI - Nucleotide sequence of a cDNA clone encoding a rabbit immunoglobulin-lambda light chain: the V lambda region differs markedly from that of other species. AB - A cDNA clone (pDH7) has been isolated which encodes the entire leader peptide and variable (V) region and most of the constant (C) region of a rabbit lambda-light chain. Although similar to amino acid sequences derived from fragments of isolated lambda-chains from several Basilea rabbits, differences in the first framework region (FR1) suggest that at least two germ-line V lambda genes are expressed. There are major differences between rabbit V lambda sequences and light chains of other species: in particular, rabbit lambda-chains have an additional four amino acids in the vicinity of the FR2-CDR2 junction. The same region also has significant homology with the human D2 germ-line mini-gene sequence, especially with a 14-nucleotide sequence previously shown to be homologous to human and rabbit heavy chain CDR2 sequences. Similar homologies in other heavy and light chain sequences suggest that D-gene segments may be derived from VH genes, perhaps by transposition. The framework regions of the rabbit lambda-chain encoded by clone pDH7 show the greatest homologies with those of human kappa- and lambda-sequences (46 to 54% homology), with that of chicken sequence (55%), and least with murine V lambda sequences (40%). PMID- 3104460 TI - Eleven MRL-lpr/lpr anti-DNA autoantibodies are encoded by genes from four VH gene families: a potentially biased usage of VH genes. AB - The genes encoding 11 independently derived anti-DNA autoantibodies from the lupus-prone mouse strain, MRL-lpr/lpr, were examined with VH, D, and JH gene probes. These autoantibodies do not define new VH gene families, since all of the autoantibodies were encoded by VH genes from four of the nine known gene families. A minimum of nine different VH genes encoded this panel of 11 anti-DNA autoantibodies. These results are consistent with the stochastic use of the VH gene repertoire and the expression of multiple VH genes. However, the data is also consistent with a biased usage of the VH gene repertoire. First, two pairs of autoantibodies, one from the J558 family and one from the 7183 family, appear to express identical or closely related VH genes as determined by the position of two restriction enzyme sites 5' of the expressed VH genes. In addition, three autoantibodies that appear to be sister clones might define a third VH gene that is used repeatedly. Secondly, about 45% of the panel is encoded by the Q52 and 7183 families, which are the 3' most families. These families have been shown to be preferentially rearranged early in B cell ontogeny. This suggests that some anti-DNA autoantibodies might originate from a population of B cells that predominate early in ontogeny. An alternative hypothesis is that the potential bias in VH gene and gene family usage could be due to antigen selection. All four JH genes are expressed, although the JH1 gene appears to be underutilized in both expressed and unexpressed rearrangements. Two members of the panel that bind double-stranded DNA were encoded by two different VH gene families, the S107 family and the J558 family. PMID- 3104461 TI - Selective inhibition of 28S ribosomal RNA in macrophages activated by interferon gamma or -beta. AB - We have investigated the metabolism of RNA in mouse peritoneal exudate macrophages activated by interferon (IFN)-gamma or -beta. Both species of IFN induce cytotoxic activity in macrophages. We observed a decrease in the incorporation of [3H]-uridine into total RNA in macrophages treated with doses of IFN that induce cytotoxic activity. IFN-gamma was 100-fold to 1000-fold more potent that IFN-beta in inhibiting RNA synthesis. [3H]Uridine-labeled RNA was purified from IFN-activated and control macrophages and was size fractionated on agarose gels. Macrophages activated by either IFN-gamma or IFN-beta had an imbalanced accumulation of 28S ribosomal RNA compared with their accumulation of 18S ribosomal RNA. Pulse-chase experiments suggested that IFN induced a selective inhibition of the processing of 28S ribosomal RNA. These results provide the first evidence that IFN can modulate ribosomal gene expression at the post transcriptional level. Moreover, they indicate that inhibition of 28S ribosomal RNA accumulation in macrophages is a molecular event triggered by IFN-gamma, as well as IFN-beta. PMID- 3104462 TI - Molecular events involved in regulating human interferon-gamma gene expression during T cell activation. AB - The human T cell line Jurkat is a useful model of regulated T cell activation. After in vitro treatment of Jurkat with phytohemagglutinin (PHA) and phorbol ester (PMA), RNA transcripts of both interleukin 2 (IL 2) and interferon-gamma (IFN-gamma) appear, followed by secretion of both biologically active lymphokines. Employing the nuclear run-on technology, we first confirmed that the expression of both lymphokines after T cell activation is regulated at the transcriptional level. By using the recombinant approach of DNase I hypersensitivity mapping, we had previously localized a structurally unique, lymphocyte-specific genomic domain in the first intron of the human IFN-gamma gene that correlated with the transcriptional potential of that gene. By using several T cell lines that differ in their inducible expression of IFN-gamma, we have now localized several additional structural domains within the human IFN gamma gene that appear to be coordinately involved in regulating expression. These include: a distal 5' flanking region site also seen only in T lymphocytes that can express the gene, a proximal, promoter-associated site that appears only after PHA/PMA-mediated IFN-gamma induction, and a second intronic site seen only in T cells whose IFN-gamma gene is selectively inactive. Collectively, our data suggest that T cell activation is accompanied by transcriptional level induction of lymphokine gene expression. In the case of IFN-gamma, T cell nuclei possess specific structural domains within the gene itself that seem to participate both positively and negatively in activation-mediated regulatory events. PMID- 3104463 TI - Induction, maintenance, and reinduction of tumoricidal activity in bone marrow derived mononuclear phagocytes by Corynebacterium parvum. Evidence for the involvement of a T cell- and interferon-gamma-independent pathway of macrophage activation. AB - Rat bone marrow-derived mononuclear phagocytes, virtually homogeneous with respect to the cell lineage, do not exhibit spontaneous tumoricidal activity in the resting state. When incubated with macrophage-activating lymphokines, rat recombinant interferon-gamma (IFN), or heat-killed Corynebacterium parvum, bone marrow-derived mononuclear phagocytes readily evolve tumoricidal activity. Whereas tumoricidal activity induced by lymphokines and/or rat recombinant IFN gamma is short-lived, that elicited by C. parvum is maintained for at least 2 wk, provided that the C. parvum organisms are continuously present in the culture. After washing off extracellular organisms, C. parvum-induced tumoricidal activity decays rapidly, suggesting that sustained extracellular stimulation is required for its maintenance. Induction of tumoricidal activity by macrophage-activating lymphokines and/or rat recombinant IFN-gamma is fully prevented by polyclonal and monoclonal anti-IFN-gamma antibodies; in contrast, induction by C. parvum is not affected by anti-IFN-gamma. Since induction of tumoricidal activity by C. parvum takes place irrespective of the presence of anti-Thy-1 antisera or cyclosporin A, T cells and/or their products appear not to be involved in this type of macrophage activation. Accordingly, present findings provide evidence for the existence of lymphokine-independent pathways of macrophage activation. PMID- 3104464 TI - Chemotactic factor and P15E-related chemotaxis inhibitor in human melanoma cell lines with different macrophage content and tumorigenicity in nude mice. AB - The present study was designed to characterize the production of chemoattractants by human melanoma lines with high (M4Be, M3Da, NTerDa) or low tumorigenic (Doc8, M1Do) potential when heterotransplanted in nude mice. Supernatants from the Doc8 and M1Do cell lines were strongly chemotactic in vitro for mononuclear phagocytes. Chemotactic activity was destroyed by proteolytic enzymes, and upon gel filtration on Sephadex G75, it eluted in the cytochrome c region corresponding to an apparent m.w. of 12,000. Upon chromatofocusing, the Sephadex separated tumor-derived chemotactic factor (TDCF) showed an isoelectric point of 5.5 to 6. Cell lines with high tumorigenic potential contained low or no detectable chemotactic activity. When culture supernatants of cell lines with modest (M3Da) or no (M4Be) chemotactic activity were exposed to immobilized monoclonal antibodies directed against the retroviral transmembrane protein P15E, appreciable chemotactic activity was detectable (M4Be) or preexisting levels increased (M3Da). The material eluted from Sepharose-bound anti-P15E antibodies inhibited the migration of monocytes in response to chemoattractants. These findings demonstrate the coexistence in some human melanoma cell line supernatants of factors (TDCF and P15E-related inhibitor) with opposite influence on monocyte chemotaxis. That tumor cell products play a pivotal role in regulating the extravasation of monocytes into neoplastic tissues is suggested by the close correlation observed between macrophage levels in melanomas grown in nude mice and levels of chemotactic activity detectable in culture supernatants. PMID- 3104465 TI - T cell surface markers expression by immature human thymocytes in in vitro culture: role of Ia+ accessory cells. AB - Previous studies have indicated that the human thymus is composed of several discrete compartments. Cortical thymocytes are reactive with the monoclonal antibody anti-T6, whereas most medullary cells, unreactive with anti-T6, stain brightly with anti-T3 antibody, which defines mature T cell populations. By using an indirect immune rosette method, we isolated the minor thymocyte population (1 to 2% of all thymocytes) lacking both T3 and T6 but expressing T11 antigens. These cells could be maintained in culture supplemented with recombinant IL 2 (Rec-IL 2) for several days. Under these conditions, T3-T6- cells were shown to undergo phenotypic changes. In the absence of thymic macrophage (Mo), T3+ and T8+ thymocytes appeared in culture, whereas the development of T4+ cells strictly required the presence of Mo. The expression of T4 antigen could be largely prevented by the addition of anti-HLA-DR antibody, further indicating that Ia+ accessory cells had the ability to promote in vitro development of T4+ thymocytes. In the presence of Mo, not only T4+ but also T8+ cells were obtained. Double fluorescence staining with anti-T8-FITC and anti-T4-biotin demonstrated that after 12 days of culture, T4 and T8 antigens were mutually exclusive. Furthermore, during the course of these studies, we observed that under the culture conditions utilized (e.g., presence or absence of Mo), T3-T6-thymocytes failed to express the T6 antigen. Thus, the in vitro development of T cells bearing a mature phenotype could be obtained in the absence of intermediate expression of cortical (T6+) thymocytes. PMID- 3104466 TI - The role of the T cell receptor, CD8, and LFA-1 in different stages of the cytolytic reaction mediated by alloreactive T lymphocyte clones. AB - The cytotoxic reaction mediated by cytotoxic T lymphocytes (CTL) consists of three phases: first, the CTL binds to the target cell; next, the CTL is triggered to lyse the target cell; and in the third phase, the CTL detaches from the target cell which is lysed in the absence of the CTL. Recently, we obtained evidence that human alloreactive CTL clones initially adhere to target cells without the involvement of the interaction between the T cell receptor (Tcr) and its specific target antigen. In the present study, we investigated the effect of monoclonal antibodies specific for the Tcr on the cytotoxic reaction of three CD8+ HLA-A2 specific CTL clones, using a single cell assay in which the binding event can be distinguished from the post-binding (lytic) phase of the cytolytic reaction. It was found that monoclonal antibodies directed at a variable part of the Tcr do not affect the binding phase but strongly block the lytic phase of the cytotoxic reaction. An anti-constant region Tcr antibody and an anti-CD3 reagent had a similar effect on the two phases of the reaction as the anti-variable part Tcr antibodies. In contrast, antibodies specific for LFA-1 strongly blocked the adhesion phase but did not affect the lytic phase. Antibodies specific for CD-8 had intermediate effects. They could block both the adhesion as well as the lytic phase. The effect of anti-CD8 appeared to be dependent on the CTL clone tested. One clone was found to be inhibited in the adhesion phase, but not in the lytic phase, whereas anti-CD8 hardly blocked the adhesion phase of two other CTL clones, but affected the lytic step of those clones. Our data indicate that LFA-1 is a major adhesion molecule in the CTL reaction, whereas the Tcr/CD3 complex is implicated in a phase after the initial formation of conjugates. CD8 is associated with both steps in the cytolytic reaction. In addition to its minor role in the adhesion phase, our data suggest strongly that CD-8 is involved in the triggering phase of the cytolytic reaction. PMID- 3104467 TI - In vitro and in vivo activation of human mononuclear phagocytes by interferon gamma. Studies with normal and AIDS monocytes. AB - To determine the potential immunotherapeutic role of interferon-gamma (IFN-gamma) as a mononuclear phagocyte-activating agent, we examined the effector cell function of peripheral blood monocytes from healthy donors and acquired immunodeficiency syndrome (AIDS) patients after either in vitro and/or in vivo treatment with recombinant (r) IFN-gamma. When assayed immediately after a 24-hr in vitro pulse with 300 U/ml, normal and AIDS monocytes behaved similarly with little augmentation of their intrinsically high levels of H2O2 release and activity against Toxoplasma gondii; in contrast, activity toward the more resistant intracellular pathogen, Leishmania donovani, was appreciably enhanced by rIFN-gamma. In addition, upon testing 4 to 6 days after in vitro pulsing, both normal and AIDS monocytes showed clear evidence of persistent activation in all three assays. The capacity of IFN-gamma to similarly activate monocytes in vivo was confirmed in all ten treated AIDS patients by examining cells before and after 24-hr infusions of 0.03 and 0.5 mg of rIFN-gamma/square meter (M2) of body surface area. For postinfusion monocytes tested after 1 day in culture, H2O2 release and antitoxoplasma activity were essentially unchanged, but antileishmanial effects were augmented. After 5 to 7 days in culture, monocytes from treated patients showed 3.2- to 5.9-fold increases in H2O2-releasing capacity and increases of 49 to 68% and 35 to 61% in intracellular activity against T. gondii and L. donovani, respectively. These results indicate that the human monocyte can be induced by rIFN-gamma to express signs of both immediate and persistent activation and suggest that, as a direct activator of mononuclear phagocytes, rIFN-gamma may also have potential as an immunotherapeutic agent for patients with intracellular infections. PMID- 3104468 TI - Normal trophoblasts resist induction of class I HLA. AB - Very few types of normal cells fail entirely to express class I human leukocyte antigens (HLA), and many of those cells (sperm, fetal amnion epithelial cells, and fetal trophoblasts) are related to the process of reproduction. Susceptibility of sperm to modulation of class I antigens has not been examined, but it has recently been demonstrated that amnion cells respond to exposure to IFN-gamma with readily detectable levels of class I antigens. In addition, one of two trophoblast cell lines (BeWo) has been shown to exhibit enhanced expression of class I HLA in response to IFN-gamma. Expression by a second trophoblast cell line (Jar) was not inducible. Findings in the present study included demonstration of IFN-gamma-enhanced class I-specific mRNA synthesis in JEG-3 cells, which are derived from BeWo, and failure of synthesis by Jar cells. Those results eliminated trivial explanations for the preceding findings and confirmed the responsiveness of some but not all cells of trophoblast origin to IFN-gamma. When successful modulating conditions for amnion and malignant trophoblast cells were applied to normal tissues, third trimester term chorionic cytotrophoblasts and first trimester villous syncytial and cytotrophoblasts failed to exhibit class I HLA. Neither malignant nor normal trophoblasts expressed class II HLA under any condition of testing. Failure of induction of HLA expression by normal trophoblasts could not be attributed to either loss of viability by tissue explants or failure of modulating reagents to reach the trophoblasts. The results demonstrate that regulation of expression of histocompatibility antigens by major populations of normal trophoblasts and one of two choriocarcinoma cell lines differs markedly from that of other fetal and adult cells. Uncommon regulatory mechanisms may be essential to maintenance of the trophoblast as an immunologically inert barrier between the mother and her antigenically disparate fetus. PMID- 3104469 TI - Differential effects of interferon-alpha and interferon-gamma on interleukin 1 secretion by monocytes. AB - We examined the effect of interferon (IFN)-alpha and IFN-gamma on the ability of human monocytes to secrete interleukin 1 (IL 1). IFN-alpha directly induced IL 1 secretion by monocytes. IFN-gamma did not induce any IL 1. IFN-gamma-stimulated monocyte supernatants were also negative for pyrogenic activity. However, IFN gamma greatly enhanced the amount of IL 1 secreted when monocytes were stimulated by lipopolysaccharide or Staphylococcus aureus, even at concentrations which by themselves did not induce IL 1. IFN-alpha did not enhance IL 1 secretion induced by other stimuli. IFN-gamma enhanced IL 1 secretion by priming monocytes to be more sensitive to an IL 1-inducing stimulus. However, IFN-gamma does not enhance IL 1 induced by all stimuli, because there was no enhancement of IL 1 induced by PMA. Thus, IFN-alpha and IFN-gamma have very distinct roles in the induction and enhancement of IL 1 by monocytes. PMID- 3104470 TI - Biochemical and morphological characterization of basophilic leukocytes from two patients with myelogenous leukemia. AB - Basophilic leukocytes from two patients with myelogenous leukemia were enriched to a purity of 10 to 45% by density gradient centrifugation. Ultrastructurally, these basophilic leukocytes contained segmented nuclei and granules with reticular patterns resembling those of normal basophils, and other granules with scroll and grating patterns resembling those of normal connective tissue mast cells. The 35S-labeled macromolecules isolated from these cells were approximately 140,000 m.w. Pronase-resistant proteoglycans bearing approximately 15,000 m.w. glycosaminoglycans. On incubation with chondroitinase ABC, nitrous acid, and heparinase, the 35S-labeled proteoglycans were degraded 50 to 84%, 16 to 43%, and 8 to 37%, respectively, indicating the presence of both chondroitin sulfate and heparin. As assessed by high performance liquid chromatography, the 35S-labeled chondroitin sulfate disaccharides liberated by chondroitinase ABC treatment were approximately 95% monosulfated chondroitin sulfate A and approximately 5% disulfated chondroitin sulfate E. The presence of heparin was confirmed by two-dimensional cellulose acetate electrophoresis of the 35S-labeled glycosaminoglycans. Cell preparations, enriched to 75% basophilic leukocytes by sorting for IgE+ cells, also synthesized 35S-labeled proteoglycans containing chondroitin sulfate and heparin. In one experiment, treatment of the cells with 1 microM calcium ionophore A23187 resulted in a 12% net release of both chondroitin sulfate and heparin containing 35S-labeled proteoglycans, a 57% net release of histamine, and the de novo generation of 8, 8, and 0.16 ng of immunoreactive equivalents of prostaglandin D2, leukotriene C4, and leukotriene B4, respectively, per 10(6) cells. Because only mast cells have been found to contain Pronase-resistant heparin proteoglycans, to generate PGD2 on cell activation, and to contain granules with scroll and grating patterns, these findings indicate that in some patients with myelogenous leukemia there are basophilic cells that possess properties of tissue mast cells. PMID- 3104471 TI - Characterization of regulatory (interferon-alpha/beta) and accessory (LAF/IL 1) monokine activities from liver granuloma macrophages of Schistosoma mansoni infected mice. AB - Previously it was shown that macrophages (M phi) isolated from the vigorous (Vig) or modulated (Mod) liver granulomas (Gr) of Schistosoma mansoni-infected mice restored mitogen and parasite egg antigen-induced proliferative responses to accessory cell-depleted lymphocytes. Furthermore, supraoptimal concentrations of highly activated VigGrM phi suppressed lymphoproliferation to a greater extent than did the lesser activated ModGrM phi. In this study we investigated the role of soluble mediators in GrM phi accessory/regulatory activity. Indomethacin released VigGrM phi-mediated inhibition of mitogen but not antigen-induced lymphoproliferation. Extensively dialyzed serum-free GrM phi culture supernatant nonspecifically suppressed SEA- or KLH-induced blastogenesis. Culture supernatants also reduced vesicular stomatitis virus-induced plaque formation in supernatant-pretreated L-929 fibroblasts. The 20 to 45 Kd GrM phi-derived lymphoproliferation suppressive factor (SF) and the 20 to 50 Kd viral plaque reducing factor (PRF) were stable at low pH, but became inactivated by heat and trypsin digestion. Although freshly isolated Vig or ModGrM phi contained preformed SF and PRF, in vitro production of the factors were depressed by protein synthesis inhibitors. Moreover, SF was active only when added to cultures before day 3 of the 6-day proliferation assay. Both SF and PRF were specifically retained on rabbit anti-murine IFN-alpha/beta immunoaffinity columns. Thus, the suppressive activity of Vig or ModGrM phi is in part mediated by a monokine that shares physical, biological, and antigenic characteristics with murine IFN alpha/beta. In contrast to the suppression of antigen-driven proliferation, GrM phi culture supernatant costimulated PHA-induced mitogenesis. The 13 to 21 Kd GrM phi-derived lymphocyte-activating factor (LAF) was stable to heat, low pH, and trypsin digestion. Freshly isolated Vig or ModGrM phi contained preformed LAF, although its in vitro production was depressed by protein synthesis inhibitors. The physical and biological characteristics of GrM phi-derived LAF appear similar to IL 1. It is concluded that both Vig and ModGrM phi secrete regulatory/accessory monokines that may contribute to the initiation and maintenance of the focal inflammatory granulomatous response. PMID- 3104472 TI - The antigenic and mitogenic response of murine T and B lymphocytes to soluble proteins of Listeria monocytogenes. AB - Solubilized constituents from Listeria monocytogenes were fractionated by various techniques including isopycnic gradient centrifugation, molecular sieve chromatography, and preparative SDS-polyacrylamide gel electrophoresis (SDS PAGE). Fractionated material was tested in vitro for mitogenic and antigenic activity by quantitating the proliferation of splenic lymphocytes and the interleukin production by peritoneal T cells. Fractionation by isopycnic gradient centrifugation revealed both antigenic and mitogenic material fractionating with the protein at a density of 1.3 g/ml. This characteristic density, together with the reduction of activity with trypsin treatment, defined the material as protein. This material was termed soluble listerial proteins (SLP). Fractionation of SLP by molecular sieve chromatography using Sephacryl 200 (S-200) revealed predominant antigenic and mitogenic activity in proteins of greater than 100,000 m.w. In contrast, fractionation of SLP by preparative SDS-PAGE (nonreducing conditions) showed activity in groups of proteins with m.w. of less than 76,000. This difference (S-200 vs SDS-PAGE) may indicate an aggregation or subunit composition which is disrupted by SDS. When fractionated by SDS-PAGE, antigens which induced macrophage-dependent interleukin production by Listeria-immune T cells were observed over a broad range of molecular sizes. Major groups of antigenic proteins were observed at 57,000 to 76,000 m.w., approximately 40,000 and less than 25,000 m.w. Mitogenic activity (spleen cell proliferation) was associated with a more restricted group of proteins with major peaks at 57,000 and 40,000 m.w., with some weak activity in proteins less than 20,000 and greater than 64,000 m.w. Experiments involving T or B lymphocyte-depleted spleen cells and spleen cells from athymic mice revealed that the mitogenic response of splenic lymphocytes to SLP was predominantly B cell-mediated. Thus, we have defined groups of listerial proteins with potent antigenic activity with respect to T lymphocyte activation and as mitogenic activity for B cells. PMID- 3104473 TI - Characterization of B lymphocyte lineage progenitor cells from mice with severe combined immune deficiency disease (SCID) made possible by long term culture. AB - A single gene mutation results in near absence of B and T lymphocytes and their immediate progenitors in mice with severe combined immunodeficiency disease (SCID). However, long term culture conditions allowed rapid outgrowth of lymphocytes from SCID bone marrow suspensions, and this permitted their detailed analysis. The cells were judged to be committed to the B lymphocyte lineage on the basis of expression of the BP-1 antigen, as well as by the density and pattern of expression of other markers. Cultured SCID lymphocytes were indistinguishable from control BALB/c cells in terms of morphology, typing for 13 cell surface markers, and changes in cell surface antigen expression with time in culture. In contrast to cultures of normal cells, which always included IgM synthesizing cells, SCID lymphocytes rarely expressed mu heavy chains. Southern blot analysis demonstrated that at least the first Ig gene rearrangement step had occurred in most of the cultured cells. The patterns of JH gene rearrangements suggested that relatively limited population diversity existed in individual cultures of SCID and normal BALB/c marrow. In addition, there was evidence that abnormal Ig heavy chain gene rearrangements had taken place in lymphocytes from approximately 25% of the SCID cultures. These cells were distinguished by the absence of detectable JH gene segments. kappa light chain genes appeared to be unrearranged in SCID cultured lymphocytes. We conclude that the lymphopoietic microenvironments of SCID mice are probably normal, and the animals have infrequent progenitors of B cells. Aberrant or nonproductive IgH gene rearrangements may account for the absence of pre-B and B cells in SCID mice. This study demonstrates the usefulness of long term culture methodology for isolating rare subsets of non-transformed lymphoid cells from normal and genetically defective hemopoietic tissues. PMID- 3104474 TI - Expression of a 120,000 dalton protein during tumoricidal activation in murine peritoneal macrophages. AB - Modulation of protein expression during interferon-gamma (IFN-gamma) lipopolysaccharide (LPS)-mediated macrophage tumoricidal activation has been examined by metabolic radiolabeling of various murine peritoneal macrophage populations with [35S]methionine followed by SDS-PAGE analysis. Although both IFN gamma and LPS are capable of stimulating the expression of several proteins when used independently, combined treatment induced the enhanced or de novo expression of a 120,000 dalton polypeptide. The expression of this protein was synergistically regulated by both IFN-gamma and LPS in a manner strongly reminiscent of the functional synergism that these two agents exhibit with respect to induction of tumoricidal activity. p120 expression could be seen first at approximately 3 hr after the addition of both agents, reached optimal expression by 6 hr, and maintained elevated synthesis for up to 24 hr. This time course corresponds closely to that seen for the acquisition of tumoricidal competence. Macrophages elicited in the primed state of activity in vivo with methyl vinyl ether co-polymer II (MVE-II) did not express p120, but could be induced to do so when treated with low doses of LPS. Under similar conditions, MVE-II-elicited cells also acquire tumoricidal activity. Macrophages obtained from mice chronically infected with bacillus Calmette-Guerin constitutively expressed both p120 and cytolytic activity. If such macrophages were cultured for 24 hr, the expression of both events decayed and was lost, but could be restored by treatment with low doses of LPS. Thus the data support a strong correlation between the expression by macrophages of a novel 120,000 dalton protein and the expression of tumor cytotoxicity. PMID- 3104475 TI - Immunofluorescence determination of IgG in cerebrospinal fluid following high performance liquid gel permeation chromatography. AB - A simple technique using high performance liquid gel permeation chromatography for determination of IgG in cerebrospinal fluid (CSF) is described. Accurate determination of IgG was achieved by precolumn derivatization with fluorescein isothiocyanate-conjugated anti-human IgG Fab, a substance that readily yields a fluorescent immune complex. Immune complexes separated as a well-delineated peak in the column void volume, and were measured by the fluorescence of the column eluates (Ex = 490 nm, Em = 520 nm). The results were reproducible with a deviation of less than 2% and a good linear relationship over the range of 2.0 24.5 mg/dl. The IgG concentration assayed by the column method correlated well with values obtained by laser nephelometry. PMID- 3104476 TI - A simple new method for using antigens separated by polyacrylamide gel electrophoresis to stimulate lymphocytes in vitro after converting bands cut from Western blots into antigen-bearing particles. AB - The individual antigenic components present in microgram quantities of complex mixtures can be separated reproducibly by polyacrylamide gel electrophoresis and transferred onto nitrocellulose blots. We report that the ng quantities of antigen present in single lines cut from such Western blots can be used to induce maximal lymphoproliferative responses in 30-60 microtitre wells. In order to achieve this the excised lines of antigen-bearing nitrocellulose sheet must be converted into antigen-bearing particles small enough to be engulfed by macrophages. We describe optimal conditions and discuss the applications of this technique. PMID- 3104477 TI - The generation of lipid peroxides by stimulated human neutrophils. Detection using phenol red oxidation. AB - When activated, phagocytic cells undergo a burst of oxidative metabolism, consuming oxygen and converting it to several products including superoxide anion and hydrogen peroxide. The latter may be quantified using an assay based on the oxidation of phenol red catalysed by horseradish peroxidase. This method has been employed to evaluate peroxide formation by human neutrophils activated in vitro with a variety of stimuli. Evidence is presented to show that neutrophils secrete different major peroxides depending upon the stimulus, its concentration and the incubation time. Based on inhibition studies using enzymes and drugs these may be identified as hydrogen peroxide and a lipoxygenase product, probably 5 hydroperoxyeicosatetraenoic acid (5-HPETE). Thus, phenol red oxidation may, under certain circumstances, represent a simple assay of lipoxygenase activity in stimulated human neutrophils. PMID- 3104478 TI - Expression of immunoglobulin lambda chains in the laboratory rat. AB - We immunized a BALB/c mouse with the lambda-bearing rat IgG1 myeloma IR31, fused its spleen cells with the hybridoma parent line P3.X63.Ag8.653, and isolated a monoclonal antibody (G33/11) directed against rat immunoglobulin lambda chains. We used this antibody to classify two existing rat hybridomas as lambda-bearing proteins (D4.37HL.252 and PC61.5), and isolated one new lambda-bearing rat IgM hybridoma, G36/1. All the normal inbred rat sera that were tested contained lambda-bearing Ig as detected by G33/11, at levels ranging from 1.5% to 13% of the total serum Ig, the mean value being 7.9%. This antibody will be valuable for broadening our understanding of the immunogenetics of the rat, and for the characterization of monoclonal antibodies made in this species. PMID- 3104479 TI - Simultaneous responses to TD, TI-1 and TI-2 antigens originate from both specific and multipotent precursors. AB - The classification of antigens into TD, TI-1 and TI-2 varieties raises the question of whether responses to these antigens are produced by distinct or identical subpopulations of B cells. In the present study we have examined the extent of intraclonal specificity variation in the progeny of PFC appearing after stimulation with two unrelated antigens. Mouse lymphoid cells were stimulated with pairs of TD and TI antigens, PFC were individually cultured and daughter PFC examined for their specificity. In all combinations used, PFC responding to TD antigen engendered, after 48 h of culture, a high frequency of PFC daughters expressing one or the other antibody specificity, notwithstanding the specificity of parental PFC. However, PFC responding to TI antigens seemed less subject to variation in specificity, and PFC daughters engendered after a 48 h culture period were, in the majority, of the parental specificity. These results are analysed in relation to different subpopulations of B cells. PMID- 3104480 TI - In vivo administration of interleukin 1 to normal mice depresses their capacity to elicit contact hypersensitivity responses: prostaglandins are involved in this modification of immune function. AB - The administration of pyrogenic doses of interleukin 1 (IL-1) to normal mice before contact sensitization with dinitrofluorobenzene (DNFB) resulted in a significant reduction in the intensity of the elicited contact hypersensitivity (CH) responses. Adoptive transfer experiments established no difference between normal and IL-1-pretreated mice regarding their capacity to generate splenic suppressor-cell activity and lymph node effector-cell activity in response to DNFB. However, a marked reduction in the intensity of elicited responses was observed when primed CH-effector cells, obtained from normal donors, were adoptively transferred to IL-1-pretreated recipients. This finding was paralleled by a consistent reduction in the ability of the adoptively transferred cells to infiltrate the tissue sites of antigen challenge in the IL-1-pretreated animals. Treatment of mice with indomethacin, a potent inhibitor of prostaglandin production, abrogated the capacity of IL-1 to depress CH responses following skin sensitization with DNFB. Similarly, indomethacin was also capable of abrogating the ability of IL-1 to depress CH responses of adoptive recipients of primed CH effector cells. Our results indicate that the capacity of IL-1 to depress CH responses in normal mice is due to an indomethacin-sensitive process, presumably mediated through the IL-1-induced generation and action of prostaglandins. This was supported by our finding that treatment of mice with arachidonic acid or prostaglandin E2 caused a similar type of inhibition. The mechanism(s) responsible for this effect appears to act at the efferent level of the CH response, as evidenced by the reduced capacity of CH-effector cells to infiltrate the tissue sites of antigen challenge. PMID- 3104481 TI - In vitro antibiotic susceptibility of Rickettsia rickettsii and Rickettsia conorii: plaque assay and microplaque colorimetric assay. PMID- 3104482 TI - Experimental transmission of non-A, non-B hepatitis by saliva. PMID- 3104483 TI - Factors that influence the evolution of beta-lactam resistance in beta-lactamase inducible strains of Enterobacter cloacae and Pseudomonas aeruginosa. AB - Induction ratios were determined for beta-lactamase-inducible strains of Enterobacter cloacae and Pseudomonas aeruginosa by using 10 beta-lactam agents. For E. cloacae, pre-incubation with ceftriaxone, cefoxitin, cefamandole, cefoperazone, or imipenem produced significantly larger amounts of beta-lactamase than did pre-incubation with moxalactam, clavulanate, ceftazidime, or aztreonam. For P. aeruginosa, imipenem was the best inducer, whereas ceftriaxone, piperacillin, cefoperazone, cefamandole, clavulanate, and aztreonam were poor beta-lactamase inducers. The rate of emergence of resistance by E. cloacae p99 and P. aeruginosa ATCC 27853 did not correlate with the induction ratio of the selecting agent; however, a strong correlation was noted between the mutation rate and the ratio of the MIC to the concentration of selecting antibiotic used. Emergence of resistance is related to the MIC of the antibiotic and the concentration of antibiotic used to select for resistance and is independent of the efficacy of the beta-lactam inducer. Resistant mutants arise through both beta-lactamase-dependent and -independent mechanisms. PMID- 3104485 TI - Induction of hemoglobin synthesis in K562 cells by carbon dioxide deficiency. AB - Proliferation and differentiation are inversely related in many cell culture systems. The study of inducible systems is facilitated by optimal growth conditions in order that whatever differentiation is observed may be attributed to a specific effect of the inducer, rather than to a nonspecific effect of adverse growth conditions. To investigate the role of CO2 supply in an inducible system, the K562 human leukemia cell line inducible for hemoglobin synthesis was studied at 10%, 5% and 1.5% CO2 concentrations. The lower the CO2 concentration, the higher the percentage of benzidine-positive cells but the slower the growth rate. This increase in benzidine positivity reflected hemoglobin synthesis as indicated by incorporation of 3H-leucine into globin chains. If, in addition to reducing CO2 concentration, the complete medium was replaced by a bicarbonate free medium, the percentage of benzidine-positive cells was further increased and growth further slowed. However, if endogenously produced CO2 was retained by sealing the culture vessel, these effects were mitigated. Since addition of ribosides blocked these effects, the mechanism for these effects appears to be inhibition of riboside biosynthesis due to the depletion of CO2 as a substrate. The implication of this work is that, for reproducibility in studies of inducible systems in which reduction of proliferation may itself increase the probability of differentiation, the CO2 tension, the bicarbonate concentration in the medium and the rate of egress of endogenously produced CO2 must be kept constant. PMID- 3104484 TI - Passive immune therapy for experimental Pseudomonas aeruginosa pneumonia in the neutropenic host. AB - Studies were conducted in guinea pigs, myelosuppressed by cyclophosphamide, for determination of whether passive immune therapy for Pseudomonas aeruginosa pneumonia would be useful in the setting of neutropenia. Groups of infected animals (14 per group) were treated with a single intravenous infusion of hyperimmune IgG antibody to P. aeruginosa (PA-IGIV; 500 mg/kg), tobramycin (1.7 mg/kg per 8 hr), ticarcillin (120 mg/kg per 6 hr), or combinations of these regimens. Control groups received intravenous albumin solution. Survival rates were 0% with albumin only, 0% with PA-IGIV, 43% with tobramycin (P less than .05), 86% with tobramycin plus PA-IGIV (P less than .05 vs. tobramycin alone), 7% with ticarcillin, and 43% with ticarcillin plus PA-IGIV (.05 less than P less than .10 vs. ticarcillin alone). Additive intrapulmonary killing of P. aeruginosa and prevention of bacteremia were observed in animals treated with tobramycin plus PA-IGIV compared with either treatment alone. Thus, passive immune therapy for P. aeruginosa pneumonia may be useful in the neutropenic host, but only when used in conjunction with antimicrobial agents. PMID- 3104486 TI - AIDS and the oral cavity. Epidemiology and clinical oral manifestations of human immune deficiency virus infection: a review. AB - Since the first patients with acquired immune deficiency syndrome (AIDS) were seen in 1981, the disease has been recognized as an epidemic, now considered a major health threat. This article reviews, on the basis of the literature and personal observations of 120 human immune deficiency virus (HIV) infected patients, some aspects of the HIV (HTLV III/LAV) infection with emphasis on epidemiology and clinical aspects. The clinical oral manifestations include 5 groups of lesions: fungal infections, bacterial infections, viral infections, neoplasms and lesions of unknown etiology. In total, these 5 groups comprise 34 different lesions of the oral cavity. PMID- 3104487 TI - Sarcoidosis with maxillary involvement. AB - A case of sarcoidosis with maxillary involvement is presented. The patient complained of loose teeth in the upper anterior region, while radiographs revealed a poorly defined radiolucent area round the midline of the anterior maxilla. The diagnosis was verified by histopathologic examination. PMID- 3104488 TI - Acute myelofibrosis and multiple chloromas of the mandible and skin. AB - Acute myelofibrosis is a rare clinical entity characterized by severe marrow fibrosis and peripheral blood pancytopenia. It may be very closely related to and has been considered synonymous with megakaryocytic leukemia. Chloroma is also a rare entity composed of a localized collection of immature myeloid cells and is associated with a known or covert leukemia. A patient presenting with a rare combination of acute myelofibrosis, megakaryocytic leukemia and multiple chloromas of the mandible and skin, are described. Although presenting a diagnostic challenge, their combination in one patient aids in the understanding of the myeloproliferative process. To our knowledge, this is the 3rd case of chloroma involving the oral osseous structures. PMID- 3104489 TI - Osteosarcoma mimicking fibrous dysplasia of the jaw. AB - An unusual case of osteosarcoma of the jaw in a 53-year-old man is reported. The tumor primarily occurred in the right maxilla, and spread to the right mandible. Finally, the patient died of an intracranial extension of the tumor after about 4 years. Microscopically, the tumor was well-differentiated osteosarcoma, but was suspected at first to be fibrous dysplasia. PMID- 3104490 TI - Mesenchymal chondrosarcoma. AB - 2 cases of this rare tumour in Nigerian subjects is described. Clinical features indicated relatively slow but painful growth, aggravated in 1 case by dental extractions. Radical resection was followed by 6-year survival without recurrence or overt metastasis. Microscopic differential diagnosis is discussed. PMID- 3104491 TI - Delayed healing of fractures of the mandibular body. AB - 401 mandibular body fractures occurring during a 5-year period were analysed retrospectively. Out of these, 38 fractures (9.5%) were not consolidated by 50 days and made up the delayed healing group (DHG). A control group (CG) of another 38 fractures was constituted using the first mandibular body fracture consecutively following one in the DHG. The mean time until consolidation of the fractures was 116 days in the DHG and 35 days in the CG. The 2 groups were statistically analysed and mutually compared using a great number of variables including patient-, fracture site-, treatment- and end-result characteristics. It was concluded that a few days delay between trauma and treatment did not necessarily lead to a delayed healing. Uncooperative alcoholics with psycho social handicaps, and general as well as local periodontitis, were found to be especially liable to consolidate their fractures at a slower rate than the average patient. The DHG more often required changes of unstable dental fixation, prolonged maxillo-mandibular fixation time and treatment for late infections at the fracture site. The patients in this group lost more teeth than those in the CG but above all required considerably extended therapeutic efforts. It is suggested that patients with the above-mentioned characteristics should be given special attention and care. PMID- 3104492 TI - Vasogenic facial pain (cluster headache). AB - 8 cases of vasogenic facial pain are presented with delineation of differentiating clinical features. These vasogenic syndromes include classic episodic cluster headache, chronic cluster headache, and indomethacin responsive chronic cluster headache. Open clinical trials employing inhalation O2 therapy as an abortive treatment strategy utilized in combination with prophylactic nifedipine therapy proved highly efficacious in controlling pain among most classic and chronic cluster headaches. A single case of chronic paroxysmal hemicrania responded favorably to indomethacin. PMID- 3104493 TI - Clinical findings in patients with orofacial discomfort complaints. AB - In 113 patients with orofacial and general complaints, which they assumed were caused by galvanic currents and/or metallic restorations, clinical dental and medical examinations were performed. Most of the patients had natural teeth with dental metallic restorations. A number of dental diagnoses, such as caries, pulpitis, periapical osteitis and periodontitis, were found. However, 16% were edentulous in one or both jaws and had complete dentures. 69% had possible metal contacts. Some oral mucosal changes were observed, but they were as frequent in patients without as in those with metal contact possibility. Signs of parafunctions and functional disturbances of the masticatory system were extremely frequent. A careful oral examination in these patients thus revealed many clinical dental and oral signs that could be more-or-less related to the complaints. Because of the extremely varying symptoms reported, however, only a small proportion could be fully explained by odontological and/or medical diagnoses, and in 38% of the patients, no clear odontological diagnosis was found that could explain the complaints. PMID- 3104494 TI - Suprofen versus paracetamol after oral surgery. AB - A randomized double-blind trial was performed to evaluate efficacy and tolerability of suprofen 200 mg (Suprocil) in comparison to paracetamol 500 mg after surgical extraction of a wisdom tooth. The study lasted 4 days per patient at the longest. Pain intensity and pain relief were evaluated by the patients using a visual analog scale. A total of 59 patients took part in the study; of these, 30 were on suprofen and 29 on paracetamol. The 30-min pain relief with paracetamol was superior to that obtained with suprofen. Roughly, the 90-min pain relief scores were somewhat higher for suprofen than for paracetamol. However, none of the differences were statistically significant. No significant difference was seen between the 2 treatment groups with respect to the frequency of the number of capsules taken per day. Broadly, the efficacy was good or excellent in 18 patients in each group. With suprofen, there were 8 moderate results and 4 insufficient ones. With paracetamol, 6 results were moderate and 5 insufficient or worse. No significant differences between the 2 treatments was seen. Tolerability was rated good by all but 1 patient in each treatment group; with suprofen, 1 result was moderate, while with paracetamol, 1 result was poor. Adverse reactions occurred in 3 patients on suprofen and in 2 patients on paracetamol, though these reactions could not be related to the use of the drug itself. PMID- 3104495 TI - CT scan prior to installation of osseointegrated implants in the maxilla. AB - A method using computed tomography (CT) for evaluation of maxillary structures before installation of titanium fixtures is described. This method gives us comprehensive information of relevant bony structures and bone quality. The width of the paranasal sinuses, nasal cavity and incisal canal is properly evaluated and the method facilitates measurements of available space for position, number and length of fixtures to be installed. PMID- 3104496 TI - Dental extractions in relation to radiation therapy of 224 patients. AB - The case histories of 224 patients treated with radiation therapy for head and neck malignancies at the Radiotherapy Clinic of the University Central Hospital in Turku during the years 1974-77 are reviewed. Of the 92 patients surviving for 5 years, 90 were available for re-examination. The median radiation dosage was 61 Gy in 6 to 8 weeks in patients with squamous cell carcinoma and other solid tumours and 43 Gy in 5 weeks in patients with lymphoma. The oral status of the patients was examined clinically and radiographically. From these patients, 45 teeth had been extracted before irradiation and 94 after irradiation. In no case had this resulted in osteoradionecrosis of the jaws. It is evident that the repairing of patient's teeth before radiation treatment, coupled with continuous preventive care of caries, will prevent serious complications from arising. PMID- 3104497 TI - Position of the mandibular canal. AB - Because of its numerous advantages, sagittal split osteotomy of the ramus has become the method of choice during the past 30 years. Operative injury to the vascular and nerve bundle within the mandibular canal represents a main risk factor. X-ray studies have been carried out on dry bone material to determine position of the canal. On the basis of the results, the variety of its position was ranked into 4 groups. The risk factor of, and the operative contraindication for, splitting technique in groups 3 and 4 have been emphasized. PMID- 3104498 TI - Effect of 2 episodes of cryosurgery on carcinogen-treated hamster cheek pouch. AB - Hamster cheek pouches were treated with the topical carcinogen DMBA for 8 weeks. 2 episodes of cryosurgery, located within the area of previous carcinogen application enhanced the neoplastic process by comparison with matched controls. Comparison with previous studies suggests that the 2 episodes of cryosurgery may have a greater effect in provoking overt malignancy than a single episode of cryosurgery. PMID- 3104499 TI - Suppurative osteomyelitis of the mandible in a child. AB - The rare case of osteomyelitis of the mandible in a 4-year-old boy is reported. The literature of osteomyelitis in children is reviewed and discussed. Osteomyelitis in children is mainly affected in the mandible. In childhood, mandibular structure is so immature that the inflammation of the mandible extends easily and rapidly to a wide area. It is very difficult to perform adequate treatment. The therapy for osteomyelitis in childhood must be carried out after due consideration of the stage and anatomical features. PMID- 3104500 TI - [Epidemiological studies of hepatitis Be antigen and antibody in Okinawa]. PMID- 3104501 TI - [Group A hemolytic Streptococci detected in Nemuro, Hokkaido--changes in types and variations in sensitivity to drugs over a period of approximately seven years]. PMID- 3104503 TI - [Studies on the isolation of viruses from patients suspected of influenza- isolation of influenza viruses using a suspension culture of ESK cells]. PMID- 3104502 TI - [Analysis of deep-seated mycosis in elderly patients]. PMID- 3104504 TI - [Clinical studies of pediatric staphylococcal infections. Statistical analysis of pediatric staphylococcal infections. Report 1]. PMID- 3104506 TI - [Recent prevalence of intestinal parasites in the inhabitants of Tokyo and neighboring areas]. PMID- 3104505 TI - [Clinical studies of pediatric staphylococcal infections. Clinical experience with five autopsied cases of staphylococcal infection over the last five years. Report 2]. PMID- 3104507 TI - [Effect of slime produced by Pseudomonas aeruginosa on the bactericidal activity of chlorhexidine]. PMID- 3104508 TI - [Infection in systemic lupus erythematosus]. PMID- 3104509 TI - [Experimental infection of C. psittaci (MP) strain in mice--evaluation of changes in the histopathological findings in lungs and serum antibodies in mice intranasally inoculated with C. psittaci, and comparison with histopathological findings in organs in mice inoculated by various routes of infection]. PMID- 3104510 TI - [A report on amoebiasis as an opportunistic infection]. PMID- 3104511 TI - Spontaneous platelet aggregation and coagulation parameters as risk factors for arterial occlusions in diabetics. Results of the PARD-study. AB - PARD is a prospective study sponsored by the German Research Council with the aim to establish whether spontaneously enhanced platelet aggregation or changes of other hemostatic parameters are risk factors for new vascular occlusions in diabetic patients. 363 diabetic patients (aged 45-65, 232 men, 131 women) were observed for 5 years. Of the 232 men, 53 were on diet, 104 on oral antidiabetic drugs and 75 on insulin. Of 131 women 16 were on diet, 46 on oral antidiabetic drugs and 69 on insulin. At entry clinical examination and laboratory tests were performed, covering the known risk factors for cardiovascular complications. Hemostatic tests and clinical examination were performed at 3 months' intervals. The life status was followed for all patients. Endpoints were carefully defined. Until December 31, 1984, 42 patients died, 23 from cardiovascular disease and 19 from other causes. 13 patients suffered a myocardial infarction, 10 a stroke and 53 peripheral arterial occlusions. The occurrence of new vascular occlusions was significantly higher in those men with enhanced spontaneous platelet aggregation measured by PAT III angle alpha above 40 degrees at entry as compared to those with lower values. This was not the case for women. Other hemostatic parameters, which had also some relation to cardiovascular complications, in men were fibrinogen and F. VIII R:Ag. Established risk factors for which a significant relation to cardiovascular complications was observed in this study, were smoking, duration of diabetes, diastolic blood pressure, cholesterol, triglycerides and also HbA1. The results of the PARD-study have verified the hypothesis that spontaneous aggregation is a major risk factor for future vascular occlusions in diabetic men. They also lead to the hypothesis that high levels of F. VIII R:Ag and fibrinogen are further indicators of progressive vascular disease and may be useful as predictors of new vascular occlusions in combination with such established risk factors as smoking, duration of diabetes, diastolic blood pressure, cholesterol, and triglycerides. PMID- 3104512 TI - Incidence of myocardial ischemia during carotid endarterectomy. AB - Since patients undergoing carotid endarterectomy often suffer from coronary artery disease, the detection, adequate treatment and prevention of intra and postoperative myocardial ischemia are a major concern. Effectively, the deleterious effects of intraoperative ischemic episodes have been largely documented. They may lead to arrhythmia, left ventricular dysfunction lasting several hours or myocardial infarction. Anesthesia induced by fentanyl, flunitrazepam and pancuronium and maintained with N20 and volatile anesthetics when warranted, has the advantage of preventing cardiovascular stimulation during endotracheal intubation and surgery, and of significantly decreasing the incidence of intraoperative myocardial ischemia in patients suffering from mild angina pectoris. However, with this approach, the incidence of intraoperative ischemic episodes remains high in patients suffering from disabling angina pectoris. In such cases, prophylactic i.v. nitroglycerin, administered continuously at the dose of 0.7 microgram/kg-1/min-1, optimizes myocardial oxygenation during surgery and minimizes the risk of intraoperative myocardial ischemia. PMID- 3104513 TI - [Combined therapy of bromocriptine, clomiphene citrate and HMG in normoprolactinemic amenorrhea patients who fail to respond to bromocriptine clomiphene citrate therapy]. AB - The purpose of this study is to investigate the ovulatory effect of the following three methods on 40 patients with normoprolactinemic amenorrhea patients who failed to respond to clomiphene citrate (Cl) alone. Method I is the combined therapy with bromocriptine and Cl (Brc/Cl). Method II is the combined therapy with Brc/Cl and an additional small amount of HMG (less than or equal to 300 IU). Method III is the combined therapy with Brc/Cl and an increased amount of HMG (less than or equal to 1,200 IU) and HCG. The ovulation rate of method I was 57.5% (23/40) in 40 cases, and 55.6% (99/178) in 178 cycles. The pregnancy rate for this method was 23.8% (5/21). Out of the 12 nonrespondent method I cases, 5 additional cases were ovulated by method II and 3 cases were ovulated by method III. The total pregnancy rate was 42.9% (9/21) with these three methods. Seven cases were normal pregnancies, one case was a twin pregnancy and 1 case was an abortion. No other side effects were found in this study. From these results, the combined therapy with Brc/Cl or Brc/Cl + HMG had almost the same ovulatory rate as the HMG-HCG therapy, and fewer side effects. PMID- 3104514 TI - Heterogeneous expression of Leu3/T4 antigen on cord T cells. PMID- 3104516 TI - [The pharmacological effects of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on the function of immunocompetent cells. 1. The mitogenic response of thymocytes or spleen cells of young rats injected with EHDP]. PMID- 3104515 TI - The relation between allergy and immunity in leprosy. PMID- 3104517 TI - Suppressive effect of interferon-beta on development of tumoricidal activity in mouse macrophages. AB - The suppressive effect of IFN-alpha and IFN-beta on the induction of tumoricidal activity in mouse bone marrow-derived macrophages was investigated. Macrophages incubated for 24 hr with IFN-beta developed lower levels of cytolytic activity when stimulated with IFN-gamma and LPS, in comparison with macrophages pretreated with medium. The suppressive effect was dependent on the pretreatment dose of IFN beta over a concentration range of 1 to 1,000 U/ml. Analysis of IFN-gamma dose response curves of IFN-beta treated macrophages showed that these cells were less sensitive to IFN-gamma. The suppressive effects were fully neutralized by an antiserum to IFN-alpha/beta. Prostaglandins were apparently not involved in this process since the addition of indomethacin to IFN-beta treated macrophages did not prevent the loss of responsiveness to activating stimuli. In contrast to the results obtained with IFN-alpha and IFN-beta, macrophages pretreated with IFN gamma did not develop lower levels of cytolytic activity when again stimulated with IFN-gamma and LPS. These observations provide evidence for a potentially important negative regulatory role for IFN-alpha and IFN-beta in macrophage activation for tumor cell killing. PMID- 3104518 TI - Distribution and localization of lecithin:cholesterol acyltransferase and cholesteryl ester transfer activity in A-I-containing lipoproteins. AB - Two types of A-I-containing lipoproteins are found in human high density lipoproteins (HDL): particles with A-II (Lp(A-I with A-II] and particles without A-II (Lp(A-I without A-II]. We have studied the distribution of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer (CET) activities in these particles. Lp(A-I with A-II) and Lp(A-I without A-II) particles were isolated from ten normolipidemic subjects by anti-A-I and anti-A II immunosorbents. Most plasma LCAT mass (70 +/- 15%), LCAT (69 +/- 16%), and CET (81 +/- 15%) activities were detected in Lp(A-I without A-II). Some LCAT (mass: 16 +/- 7%, activity: 17 +/- 8%) and CET activities (7 +/- 8%) were detected in Lp(A-I with A-II). To determine the size subspecies that contain LCAT and CET activities, isolated Lp(A-I with A-II) and Lp(A-I without A-II) particles of six subjects were further fractionated by gel filtration column chromatography. In Lp(A-I without A-II), most LCAT and CET activities were associated with different size particles, with the majority of the LCAT and CET activities located in particles with hydrated Stokes diameters of 11.6 +/- 0.4 nm and 10.0 +/- 0.6 nm, respectively. In Lp(A-I with A-II), most of the LCAT and CET activities were located in particles similar in size: 11.1 +/- 0.4 nm and 10.6 +/- 0.3 nm, respectively. Ultracentrifugation of A-I-containing lipoproteins resulted in dissociation of both LCAT and CET activities from the particles. Furthermore, essentially all CET and LCAT activities were recovered in the non-B-containing plasma obtained by anti-LDL immunoaffinity chromatography. This report, therefore, provides direct evidence for the association of LCAT and CET protein with A-I-containing lipoproteins. Our conclusions pertain to fasting normolipidemic subjects and may not be applicable to hyperlipidemic or nonfasting subjects. PMID- 3104519 TI - Isolation and characterization of the fatty acid binding protein from human heart. AB - We have isolated in pure form a fatty acid binding protein (FABP) from human cardiac muscle. After preparation of a 100,000 g supernatant fraction, the procedure required only one gel chromatographic (Sephacryl S 200) and two cation exchange (CM-Sephadex C 50) steps. The recovery of FABP was 55%. Pure FABP (12.5 mg) was obtained from a 1-g of dry powder equivalent of the high-speed supernatant. The protein had an Mr of 15,500 +/- 1,000 Da and an isoelectric point of 5.3. The properties of human cardiac FABP, i.e., molecular mass, isoelectric point, amino acid composition, ultraviolet spectrum, and affinities for hydrophobic ligands, were close to those found for FABPs from bovine heart (Jagschies et al. 1985. Eur. J. Biochem. 152: 537-545). In addition, immunological cross-reactivities showed a relationship between FABPs from several mammalian heart tissues. The data elaborated by us and others support the existence of a cardiac-type FABP that is distinct from the well-defined hepatic type and gut-type FABPs. PMID- 3104520 TI - Phospholipid transfer activities in toad oocytes and developing embryos. AB - The role of lipid transfer proteins during plasma membrane biogenesis was explored. Developing amphibia embryos were used because during their growth an active plasma membrane biosynthesis occurs together with negligible mitochondrial and endoplasmic reticulum proliferation. Sonicated vesicles, containing 14C labeled phospholipids and 3H-labeled triolein, as donor particles and cross linked erythrocyte ghosts as acceptor particles were used to measure phospholipid transfer activities in unfertilized oocytes and in developing embryos of the toad Bufo arenarum. Phosphatidylcholine transfer activity in pH 5.1 supernatant of unfertilized oocytes was 8-fold higher than the activity found in female toad liver supernatant, but dropped steadily after fertilization. After 20 hr of development, at the stage of late blastula, the phosphatidylcholine transfer activity had dropped 4-fold. Unfertilized oocyte supernatant exhibited phosphatidylinositol and phosphatidylethanolamine transfer activity also, but at the late blastula stage the former had dropped 18-fold and the latter was no longer detectable under our assay conditions. Our results show that fertilization does not trigger a phospholipid transport process catalyzed by lipid transfer proteins. Moreover, they imply that 75% of the phosphatidylcholine transfer activity and more than 95% of the phosphatidylinositol and phosphatidylethanolamine transfer activities present in pH 5.1 supernatants of unfertilized oocytes may not be essential for toad embryo development. Our findings do not rule out, however, that a phosphatidylcholine-specific lipid transfer protein could be required for embryo early growth. PMID- 3104521 TI - Quantitation of lyso-platelet activating factor molecular species from human neutrophils by mass spectrometry. AB - Two physicochemical methods have been developed for the quantitative analysis of lyso-platelet activating factor (lyso-PAF) based on gas-liquid chromatography mass spectrometry (GLC/MS) and fast atom bombardment-mass spectrometry (FAB/MS) using stable isotope dilution. After addition of deuterated internal standards, lyso-PAF produced from neutrophils was purified by silicic acid chromatography and thin-layer chromatography (TLC). The GLC/MS assay employed phospholipase C or hydrofluoric acid for hydrolysis of the phosphocholine moiety to yield ether monoglycerides. Condensation of monoglycerides with acetone yielded the 1-O-alkyl 2,3-isopropylidene glycerol which could be analyzed by GLC/MS. The ions corresponding to M-15 fragments for both the labeled and unlabeled derivatives were monitored in a selected ion recording mode. Standard curves were found to be linear over the range tested (10-2000 ng) with a limit of detection found to be below 200 pg injected on column. For the FAB/MS assay, the unmodified lyso-PAF was well suited for direct analysis; however, the limit of detection (S/N greater than 3) using a glycerol matrix was found to be 5 ng placed on the probe tip. It was found that human neutrophils contain approximately 300 pg/10(6) cells which increased 2-3-fold during the 5-min period following challenge with 1.9 microM calcium ionophore, A23187. Two molecular species of lyso-PAF were identified as hexadecyl and octadecyl ethers at sn-1 with the octadecyl molecular species of lyso-PAF predominating in abundance after stimulation. PMID- 3104522 TI - The current state of sealant research. PMID- 3104523 TI - New DRG proposal expanded to physicians? PMID- 3104524 TI - Levels of LH-releasing hormone in hypophysial stalk plasma during an oestrogen stimulated surge of LH in ovariectomized rats. AB - Treatment of ovariectomized rats with 50 micrograms oestradiol benzoate, followed by 20 micrograms oestradiol benzoate 3 days later, induced surges of LH and FSH on the day following the second injection with oestradiol benzoate. During this surge of gonadotrophins, which was not blocked by the anaesthetic required to collect hypophysial stalk blood, increased hypophysial stalk plasma levels of immunoreactive LHRH were noted. Furthermore, the levels of LHRH in hypophysial portal blood were found to fluctuate. Measurement of LHRH in a pool of portal plasma revealed similar results when determined by radioimmunoassay and by a sensitive in-vitro bioassay. To mimic the observed release of LHRH during the surge of gonadotrophins, LHRH was infused, either systemically or directly into a long portal vessel, into oestrogen-treated, ovariectomized rats which had their endogenous release of LHRH blocked by pentobarbitone. An infusion of LHRH into the jugular vein, resulting in peripheral levels of LHRH which were somewhat lower than those measured in hypophysial stalk plasma, caused a surge of FSH similar to that found in rats used for collection of hypophysial stalk blood. When compared with the values in the latter animals, however, the levels of LH became two to four times higher by this infusion of LHRH. When LHRH was infused directly into a long portal vessel to mimic the observed secretion rate of LHRH during the oestrogen-stimulated surge of gonadotrophins, then the surges of LH and FSH were lower than those observed in the rats used for collection of stalk blood. PMID- 3104525 TI - The chemical reactions of irrigants used for root canal debridement. PMID- 3104526 TI - The effects of forced activity on circulating catecholamines and pH and water content of erythrocytes in the toad. AB - In vivo experiments were carried out to determine the effect of forced activity on circulating catecholamine levels, haematocrit, and the pH and water content of erythrocytes in the toad, Bufo marinus. In addition, the effect of the beta adrenergic agonist isoproterenol on erythrocyte pH and water content was examined in vitro. Forced activity caused a significant decrease in both whole blood and erythrocyte pH, while haematocrit and circulating adrenaline and noradrenaline levels increased. Erythrocyte water content did not change following forced activity. Addition of isoproterenol to toad blood in vitro had no effect on either erythrocyte pH or water content. The apparent absence of beta-adrenergic effects on erythrocyte pH and water content in the toad is in sharp contrast to the response of teleost fish erythrocytes to beta-adrenergic stimulation. The significance of these differences is discussed. PMID- 3104527 TI - Endocytosis and recycling of the T3-T cell receptor complex. The role of T3 phosphorylation. AB - An assay has been developed to assess the dynamics of cell surface glycoproteins, in which neuraminidase digestion of intact cells is used to determine the fate of cell surface molecules initially labelled via lactoperoxidase-catalyzed iodination. This approach has been used to demonstrate the constitutive endocytosis and recycling of the T3-T cell receptor (T CR) complex on the human T leukemic cell line HPB-MLT. Stable populations of both phosphorylated and nonphosphorylated forms of the T3 gamma peptide have been identified in these cells. Whereas the former are constitutively endocytosed, the latter appear to be excluded from this pathway. The results presented indicate that T3 gamma phosphorylation may control the endocytosis and recycling of the T3-TCR complex on this cell line. PMID- 3104528 TI - Expression of c-fos protooncogene in normal human peripheral blood granulocytes. AB - We have investigated by Northern blot analysis the expression of c-fos protooncogene in human peripheral blood polymorphonuclear leukocytes (PMN). Freshly isolated PMN, unlike highly purified circulating lymphoid cells, showed high levels of c-fos transcripts. Appreciable c-fos mRNA was detected in monocytes, but in lesser amounts compared with PMN. Upon exposure to a series of agents that functionally stimulate granulocytes (PMA, inactivated streptococci, TNF, granulocyte and granulocyte/macrophage colony-stimulating factor), a considerable increase in c-fos transcripts was detected. Expression of c-fos in PMN was superinduced by exposure to cycloheximide. These data indicate that the myelomonocytic differentiation pathway c-fos expression is not peculiar to monocytes/macrophages and that PMN may represent a suitable system with which to investigate the link between protooncogene expression and functional activation. PMID- 3104530 TI - Evaluation of the demented patient. AB - An adequate history from the patient and a family member, an examination for signs and symptoms suggestive of contributing organic disease, plus an individualized diagnostic battery of laboratory tests are sufficient workup for most patients presenting with the dementia syndrome. Electroencephalography, computerized axial tomographic scanning, or psychometric testing are not usually required. The results of eight studies investigating demented individuals are reviewed. Across these studies, 56 percent of cases were attributable to primary dementia, 15 percent were secondary to reversible causes, 13 percent were secondary to irreversible conditions, and 15 percent of individuals had been wrongly labeled demented. Of reversible dementias including depression, 56 percent of patients improved with therapy. Metabolic disorders were associated with about 25 percent of reversible dementias and accounted for less than 5 percent of all patients investigated for the dementia syndrome. PMID- 3104529 TI - The cellular receptor (CD4) of the human immunodeficiency virus is expressed on neurons and glial cells in human brain. AB - The expression of the CD4 antigen in normal human brain was investigated in parallel by immunohistochemical and Northern blot analyses. With anti-CD4 antibodies detecting different epitopes of the molecule, CD4+ neurons were defined in the cerebellum, thalamus, and pons. CD4+ glial cells were identified in the thalamus and pons. CD4-specific mRNA was detected in all three subareas and in the hippocampus, while other subareas were negative. The CD4+ cells were negative with anti-T cell antibodies (anti-CD2 and anti-CD8), as well as with antimonocyte antibodies (M-M 522 and M-M 42). PMID- 3104531 TI - Effect of mammalian gonadotropins on testosterone secretion in male alligators. AB - Male farm-reared alligators were injected with mammalian FSH, LH, hCG, prolactin, or saline. A blood sample was taken immediately prior to injection of hormone and at 24 h postinjection. Testosterone concentrations in the plasma were then determined by radioimmunoassay. Only the alligators injected with FSH showed a significant increase in plasma testosterone. In a second series of experiments male alligators were injected with ovine LH, ovine FSH, or saline and bled at 0, 2, 4, 16, and 24 h postinjection. Again, only the alligators injected with FSH showed significant increases in plasma testosterone at 16 and 24 h postinjection. Mammalian LH does not appear to stimulate testosterone secretion in male alligators. PMID- 3104533 TI - Hepatitis delta (delta) cDNA clones: undetectable hybridization to nucleic acids from infectious non-A, non-B hepatitis materials and hepatitis B DNA. AB - Hepatitis Delta (delta) cDNA clones were hybridized to RNA extracted from livers of chimpanzees infected with the blood-borne Non-A, Non-B hepatitis (NANBH) agent(s) and to total nucleic acids extracted from chimpanzee plasma containing a high titer of these NANBH agent(s). Since no hybridization was observed, the data suggests that the hepatitis Delta viral genome is not closely related to the genome(s) of the NANB agent(s). Our studies, in which the Hepatitis B virus genomic DNA was hybridized to hepatitis Delta cDNA clones, also confirm and extend previous studies [Hoyer et al, 1983], which report a lack of detectable homology between the hepatitis Delta genome and HBV DNA. PMID- 3104532 TI - Non-A, non-B hepatitis in Omdurman, Sudan. AB - One-hundred nineteen patients (cases) at least 13 years of age with acute hepatitis were studied to determine the viral etiology of acute hepatitis in Omdurman, Sudan. Ninety-eight control subjects (controls) were also evaluated to determine the risk factors associated with the development of clinical disease. Acute hepatitis non-A, non-B was diagnosed in 88 cases (73.9%), hepatitis B in 15 cases (12.6%), delta infection in 15 (12.6%), and hepatitis A in just one patient (0.8%). A higher percentage of hepatitis B cases had received a parenteral injection for medical therapy during the previous 6 months than control subjects (26.7% vs 4.1%, p less than 0.05). The data in this study indicate that hepatitis non-a, non-B may be the major cause of acute hepatitis in adults in this area of Sudan. The suggested association of parenteral therapy with the transmission of hepatitis B could have important implications for the spread of other parenterally-transmitted diseases. PMID- 3104535 TI - Stupor and affective state: alleviation of psychomotor disturbances by lorazepam and recurrence of symptoms after Ro 15-1788. AB - In a single patient suffering from a major depressive episode with melancholia (DSM-III), both severe psychomotor symptoms, such as stupor and mutism, and mood disturbances could be abolished completely and promptly by administration of the benzodiazepine lorazepam. Remission of symptoms was entirely and immediately reversed by the benzodiazepine antagonist Ro 15-1788. These drug effects were constantly reproducible. Possible mechanisms of action and the influence of GABAergic neurotransmission on affective and psychomotor state are discussed. PMID- 3104534 TI - Etiological types and clinical and epidemiological features of acute viral hepatitis in Xi'an in China. AB - The etiological types and some features of 163 in-patients with acute viral hepatitis in Xi'an in China are reported. Hepatitis A (HA) accounted for 89.2% in the age group 0-15 years, whereas hepatitis B (HB) mainly occurred at the age of 16 to 30 and non-A, non-B hepatitis 31 to 50. This is different from the age distribution in western countries. The cause of the difference is discussed. The transmission factors of NANB hepatitis might be different from those of HA and HB. Fever was more often seen in HA than in HB and NANB, while the maximal bilirubin was higher in HB than in NANB. Hepatic dysfunction of all three types of hepatitis seemed to be closely associated with the age of the patients. Of ten cases with fulminant hepatitis, none was due to hepatitis A; nine were adults. PMID- 3104536 TI - Differential effects of haloperidol, clozapine, and fluperlapine on tuberoinfundibular dopamine neurons and prolactin secretion in the rat. AB - Two atypical neuroleptic agents, clozapine and fluperlapine, produced rapid elevations in plasma PRL concentrations that were similar in magnitude to those produced by haloperidol. However, the PRL response to clozapine or fluperlapine was of much shorter duration than that elicited by haloperidol. Clozapine, but neither fluperlapine nor haloperidol, produced a rapid increase in the activity of tuberoinfundibular dopamine (TIDA) neurons, as evidenced by an enhanced accumulation of dihydroxyphenylalanine (DOPA) in the median eminence after the inhibition of DOPA decarboxylase. The clozapine-induced increase in DOPA accumulation was evident within 30 minutes after its administration and persisted for at least 4 hours. The clozapine-induced increase in the activity of TIDA neurons may account, in part, for the abbreviated PRL response to this neuroleptic. In addition, ability to produce a short-lived increase in PRL secretion in the rat appears to be common to the atypical neuroleptic drugs. PMID- 3104537 TI - The influence of acute and subchronic administration of various antidepressants on early morning melatonin plasma levels in healthy subjects: increases following fluvoxamine. AB - The influence of various antidepressants on the morning levels of plasma melatonin was studied in human volunteers after acute and subchronic administration in weekly increasing doses over a period of three weeks. Two monoamine oxidase (MAO) inhibitors (tranylcypromine: irreversible type A and B; pirlindole: reversible type A), two reuptake inhibitors (maprotiline: selective for noradrenaline; fluvoxamine: selective for serotonin) and an alpha 1/alpha 2 adrenergic and serotonin S2-receptor antagonist (mianserin) were administered to groups of 4 to 7 healthy volunteers each. Two hours after a single oral dose at 9 a.m., at the end of each week and one week after the last dose, morning levels of melatonin were measured using a radioimmunological method. In addition, platelet MAO activity and the uptake of 14C-5-HT into platelets were determined. Plasma melatonin concentrations at 9 a.m. were significantly increased after the intake of 150 mg fluvoxamine the night before; whereas, administration of the same dose in the morning did not lead to increases in melatonin during the day. Following subchronic administration, plasma melatonin levels were significantly increased after the 1st (50 mg/day), 2nd (100 mg/day) and 3rd (150 mg/day) week of fluvoxamine intake in comparison to pre-drug levels. No changes in early morning levels of plasma melatonin were measured in the subjects receiving the other antidepressants, after acute as well as after subchronic administration. The results seem to indicate that following fluvoxamine intake at night, the early morning decline of melatonin is delayed. It is suggested that the underlying mechanism leading to a rise in morning melatonin levels cannot be explained solely on the basis of an inhibition of 5-HT reuptake and that other pharmacological properties of fluvoxamine may be involved. PMID- 3104538 TI - Estimation of apparent quadrupolar coupling constants for complexes of magnesium ions with mono- and dicarboxylic acid ligands. Applications to magnesium ion: protein interactions. AB - 25Mg+2 ion NMR studies of complexes of magnesium ions with acetate and malonate ligands have yielded apparent quadrupolar coupling constants, chi, of approximately 1.5 MHz. The aquo magnesium ion yields a smaller chi value of 0.12 MHz, consistent with its expected higher symmetry. chi values for magnesium ion: acetate and magnesium ion: malonate complexes are utilized to calculate observed linewidths for magnesium ion: bovine prothrombin fragment 1 and magnesium ion: human Factor XII interactions. These calculated values are compared with observed values and implications of the agreement are discussed. PMID- 3104539 TI - Effect of intranigral administration of 6-hydroxydopamine and 5,7 dihydroxytryptamine on rat brain tryptamine. AB - Earlier experiments have shown that unilateral electrolytic lesions of the substantia nigra result in significant reductions in the rate of accumulation of rat striatal tryptamine. For elucidation of the type of neuronal degeneration that is associated with tryptamine depletion, the effects of intranigral injections of 6-hydroxydopamine or 5,7-dihydroxytryptamine, which would affect, respectively, dopamine- or indoleamine-containing neurons, have been assessed. Nigral 6-hydroxydopamine lesions resulted in an ipsilateral reduction in the rate of accumulation of striatal tryptamine, but no changes were observed after nigral injections of 5,7-dihydroxytryptamine. The present results suggest that decreases in the pargyline-induced accumulation of striatal tryptamine may be associated with lesions of the nigral dopamine-containing cell bodies. Alternatively, there may exist specific tryptamine-containing neurons that are damaged by 6 hydroxytryptamine and unaffected by 5,7-dihydroxytryptamine. PMID- 3104540 TI - Highly sensitive immunoassay for the alpha subunit of the GTP-binding protein go and its regional distribution in bovine brain. AB - Antisera were raised in rabbits against the alpha subunit of a GTP-binding protein, Go. Because the antisera cross-reacted weakly with the alpha subunit of inhibitory GTP-binding protein of adenylate cyclase (Gi), they were purified with a Go alpha-coupled Sepharose column. Purified antibodies reacted only with Go alpha and did not cross-react with the Gi alpha subunit or beta gamma subunits in an immunoblot assay. Using these purified antibodies, a highly sensitive enzyme immunoassay method for the quantification of bovine brain Go alpha was developed. The assay system consisted of polystyrene balls with immobilized antibody F(ab')2 fragments and the same antibody Fab' fragments labeled with beta-D-galactosidase from Escherichia coli. The minimal detection limit of the assay was 0.1 fmol, or 4 pg. The assay was specific for Go alpha, and it did not cross-react with Gi alpha or beta gamma. Samples from various regions of bovine brain were solubilized with 2% sodium cholate and 1 M NaCl, and the concentrations of Go alpha were determined. Go alpha was detected in all the regions, and the highest concentration was observed in the cerebral cortex. The immunohistochemical study showed that the neuropil was rich in Go alpha. PMID- 3104541 TI - Ossification of the posterior longitudinal ligament: a clinico-radiological study of 74 cases. AB - A clinico-radiological analysis of 74 cases of ossification of the posterior longitudinal ligament is reported. Eighteen cases (24%) were asymptomatic or only had neck or shoulder pain; 16 cases (22%) showed signs of radiculopathy, and the remaining 40 cases (54%) had myelopathy. Ossification of the posterior longitudinal ligament developed most frequently at C5, and was rare in thoracic and lumbar regions. Ossification of the posterior longitudinal ligament led to stenosis of the spinal canal; more marked stenosis caused clinical myelopathy. The data showed that 30% of stenosis caused by ossification of the posterior longitudinal ligament was critical for the production of myelopathy. PMID- 3104542 TI - Chorea and the lupus anticoagulant. PMID- 3104543 TI - Apnoea testing to confirm brain death in clinical practice. PMID- 3104544 TI - Phase II studies of recombinant human interferon gamma in metastatic renal cell carcinoma. AB - Thirty-three patients with metastatic renal cell carcinoma were treated with recombinant human interferon gamma (rIFN gamma) in two sequential, nonrandomized phase II studies. Fifteen patients received rIFN gamma by daily i.m. injection in doses ranging from 0.25 to 1.0 mg/m2, and 18 patients received it by daily continuous i.v. infusion in doses ranging from 0.01 to 0.05 mg/m2. Partial remissions were achieved by one of 14 (7%) evaluable patients in the i.m. study and in one of 16 in the i.v. study (6%). The incidence of clinical toxicity was similar for both studies. Toxicity was severe in patients receiving rIFN gamma by the i.m. route at 1.0 mg/m2 and by the i.v. route at 0.05 mg/m2. Toxicity includes constitutional symptoms (fatigue, anorexia, weight loss), leukopenia, abnormalities in liver function tests, and hypertriglyceridemia. At the doses and schedules used, rIFN gamma had minimal therapeutic activity as a single agent in metastatic renal cell carcinoma. PMID- 3104545 TI - Altered blood-nerve barrier permeability to small molecules in experimental diabetes mellitus. AB - Permeability-surface area products (PA) were determined with a quantitative in vivo injection technique at the blood-nerve barrier of tibial nerve, and at the blood-brain barrier, in control and streptozotocin-induced diabetic rats. The PA product for [14C]mannitol at the blood-nerve barrier was increased by 100% in diabetic animals, 3.12 +/- 0.15 X 10(-5) ml X s-1 X g-1, compared with controls, 1.61 +/- 0.10 X 10(-5) ml X s-1 X g-1. In contrast, PA for [14C]mannitol at the blood-brain barrier was unaltered in the diabetic animals. Following intravenous injection, no leakage of microperoxidase across the perineurium or endoneurial vessels of diabetic rats could be demonstrated by morphological techniques. Nerve blood-space, as determined with intravenous [3H]inulin, and blood-nerve barrier surface area as determined by morphometric methods, did not differ in diabetic when compared to control animals. Thus, the calculated permeability coefficient for [14C]mannitol at the blood-nerve barrier was about 100% greater in diabetic nerve compared to control nerves. The increased permeability was accompanied by a 7% increase in nerve-water content and a 32% decrease in motor-nerve conduction velocity. The results demonstrate a specific vulnerability of nerve as compared to brain in an animal model of diabetes mellitus. Chronically altered permeability to small water-soluble molecules reduces the protective effect of salt impermeability at the blood-nerve barrier against nerve edema, and may be an important pathogenic mechanism in diabetic neuropathy. PMID- 3104546 TI - Gonadal function after surgery and chemotherapy in men with stage II and III nonseminomatous testicular tumors. AB - The gonadal functions were studied in 54 patients with disseminated nonseminomatous testicular tumors who had been subjected to combination chemotherapy (cisplatin, vinblastine, and bleomycin [PVB]) and surgery (hemiorchiectomy, retroperitoneal lymph node dissection or removal of retroperitoneal residual tumor after chemotherapy) and in 17 patients with a stage I tumor subjected to hemiorchiectomy exclusively. In the patients treated with chemotherapy, the plasma testosterone levels remained at the lower limit of normal and the luteinizing hormone (LH) levels remained elevated for 2 years after completion of treatment. The follicle-stimulating hormone (FSH) levels also remained significantly elevated, but showed a tendency to decrease after 2 years. Semen analysis was performed in 25 patients; of the other patients, 18 had no antegrade ejaculation, eight had undergone a vasectomy and three patients did not cooperate. Before treatment, 72% of the patients showed azoo- or oligozoospermia; 2 years after discontinuation of the chemotherapy, 48% had azoo- or oligozoospermia while 28% had more than 60 X 10(6) spermatozoa/mL. However, interestingly the proportion of patients with azoospermia had increased from 4% to 28%. In the course of this study, eight pregnancies occurred; one ended in an early spontaneous abortion; the other seven pregnancies ran an uncomplicated course. Seven healthy children were born. In 17 patients with a stage I tumor treated by hemiorchiectomy only, the testosterone, LH and FSH levels were also observed for 2 years; until 2 years after treatment, the testosterone levels remained lower and the FSH levels remained higher than normal. Insufficiency of the Leydig's cells in the unaffected gonad appeared to be responsible for the altered hormone concentrations in the blood. PMID- 3104547 TI - Hypoxanthine:guanine phosphoribosyltransferase activity in primary human osteosarcomas. A rationale for therapy with methotrexate-thymidine rescue? AB - Hypoxanthine:guanine phosphoribosyltransferase (HPRT) activity was measured in 14 human osteosarcomas to test whether a subset of these tumors was deficient in the purine salvage pathway enzyme and thus provide a rationale for therapy with methotrexate-thymidine rescue. All tumors contained HPRT activity within the range previously reported for xenografts of human osteosarcoma. Three patients received methotrexate (3.375 g/m2/24 hours) as a 72-hour continuous infusion with thymidine rescue (2.0 g/m2/24 hours) beginning 24 hours after the start of the methotrexate infusion. The methotrexate-thymidine infusion was well tolerated by all patients with no significant toxicity; however, there were no responses. We conclude that osteosarcomas are not deficient in HPRT activity. Therefore, the previously reported rationale for therapy of osteosarcoma with methotrexate thymidine based on lack of activity of this enzyme is not valid. This combination, although well tolerated, is inconvenient and requires prolonged hospitalization. Therefore, without a valid rationale it cannot be recommended for therapy of patients with osteosarcoma. PMID- 3104548 TI - Chemotherapy administered in conjunction with osmotic blood-brain barrier modification in patients with brain metastases. AB - Clinical experience in seven patients with systemic malignancies (breast, lung and testicular) metastatic to the central nervous system treated with chemotherapy given in association with reversible osmotic blood-brain barrier modification is reviewed. A combination chemotherapy regimen including intra arterial methotrexate, intravenous cytoxan and oral procarbazine in conjunction with intra-arterial mannitol infusions was successfully carried out with minimal toxicity. The results in these patients demonstrate some therapeutic efficacy to the increased drug delivery achieved with this technique. Although suggestive, additional studies will be required to confirm that barrier modification is a key parameter in such efficacy. PMID- 3104549 TI - Immunocytochemical localization of factor VIII-related antigen in tumors of the human central nervous system. AB - Using both immunohisto- and immunocytochemical techniques with periodate-lysine paraformaldehyde (PLP) fixation, we have studied the distribution of Factor VIII related antigen (FVIIIR:Ag) in 12 cases of tumors of the human central nervous system (CNS) and one sample of non-tumor brain tissue. FVIIIR:Ag was found both extracellularly and intracellularly. It was localized in the vascular lumen, between endothelial cells, and in the endothelial cell basement membrane. In the endothelial cell cytoplasm, FVIIIR:Ag was found in the endoplasmic reticulum, perinuclear space, and in intracytoplasmic vacuoles and vesicles. Characteristic of malignant tumors (six out of seven) was a strongly-positive dilated endoplasmic reticulum. This may reflect increased FVIIIR:Ag synthesis in the endothelial cells of malignant tumors. Only one of five benign tumors showed such staining. Six of 12 tumors and the non-tumor brain showed perinuclear FVIIIR:Ag. Both ad- and abluminal vesicles in the tumor endothelial cells contained FVIIIR:Ag suggesting that endocytosis, transcellular transport, and/or endocytosis, as well as FVIIIR:Ag synthesis occurs. The non-tumor brain showed normal capillary structure and very little FVIIIR:Ag immunoreactivity. The relationship of these FVIIIR:Ag abnormalities to the hypercoagulable state seen in some malignant brain tumor patients remains to be clarified. PMID- 3104550 TI - Interruption of the connections of the mammillary bodies protects against generalized pentylenetetrazol seizures in guinea pigs. AB - Electrolytic lesions in the anterior and mid-diencephalon and ventral midbrain in guinea pigs were produced to examine the effects of interruption of the fornix (FX), mammillothalamic tracts (MT), and mammillary peduncles (MP), respectively, on the expression of pentylenetetrazol (PTZ) seizures. As a group, all mid diencephalic lesioned animals had some degree of protection from the electroencephalographic and behavioral convulsant and lethal effects of the drug. Through a composite volume analysis of protected versus unprotected animals, as well as a retrospective comparison between MT and non-MT lesioned animals, it was demonstrated that small mid-diencephalic lesions incorporating only the MTs and their immediate vicinity were capable of completely preventing the convulsant and lethal effects of PTZ. Lesions of the FX and MP were also protective against PTZ seizures but to a lesser degree than the MT lesions. These results demonstrate that the major afferent and efferent connections of the mammillary bodies are involved in expressing PTZ seizure activity and suggest that the MT may be the major pathway mediating paroxysmal activity from brain stem to the thalamus. PMID- 3104551 TI - Similarities between protein IIIa and protein IIIb, two prominent synaptic vesicle-associated phosphoproteins. AB - Protein IIIa (Mr 74,000) and protein IIIb (Mr 55,000) are 2 major phosphoproteins found in mammalian brain. It was previously shown in intact nerve cells that the phosphorylation state of these 2 proteins could be increased by electrical stimulation, by depolarizing agents in the presence of calcium, and by 8-bromo cAMP. We now report that protein IIIa and protein IIIb possess significant structural homology, as indicated by immunochemical studies using polyclonal and monoclonal antibodies and by peptide-mapping studies. A quantitative radioimmunoassay using immunolabeling in SDS-polyacrylamide gels has been used to study the tissue distribution and regional and subcellular distribution in the brain of the 2 proteins. The 2 proteins were found only in nervous tissue and the adrenal medulla. Subcellular fractionation studies suggested that both proteins are associated with synaptic vesicles. PMID- 3104552 TI - Thoracic myelopathy secondary to ossification of the spinal ligament. AB - The authors describe their experience with 26 cases of thoracic myelopathy secondary to hypertrophic ossification of the spinal ligament (posterior longitudinal ligament and/or ligamentum flavum). The clinical manifestations of this condition and results of its surgical treatment are described. The commonest symptoms were numbness or tingling in the legs and feet and gait disturbance. Most of the patients with involvement of the upper thoracic spine showed typical features of thoracic myelopathy: that is, sensory and motor deficits in both the trunk and lower extremities, sphincter disturbance, and exaggerated tendon reflexes. Several patients with involvement of the thoracolumbar junction presented with atypical symptoms of thoracic myelopathy and were sometimes misdiagnosed and treated inappropriately. Surgical treatment, particularly laminectomy, was not always successful. Inconsistencies in the surgical outcome were caused by either operative complications or reversal of the initial improvement during the follow-up period. The results of anterior surgery for the condition were more favorable; however, use of this procedure was rarely indicated. PMID- 3104553 TI - Evolution of tissue damage in compressive spinal cord injury in rats. AB - The evolution of tissue damage in compressive spinal cord injuries in rats was studied using an immunohistochemical technique and by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The rupture of small vessels accompanied by intense tissue permeation of serum components in and around the hemorrhagic foci appeared to be immediate consequences of the mechanical insult. The loss of cell membrane integrity in neural elements became evident within 1 hour after injury as shown by the diffuse albumin immunoreactivity of the cytoplasm. At the site of mechanical insult, approximately 30% of the neurofilament proteins were degraded within 1 hour, and 70% of them were lost within 4 hours after injury. A large number of cells positive for glial fibrillary acidic protein were found to demarcate the injured tissue within 1 hour after injury. The progression of tissue damage largely subsided within 48 hours. One week after injury, severe degeneration of the ascending tracts in the posterior funiculus was shown clearly by axon staining and less convincingly by myelin staining. Secondary degeneration of the corticospinal tract in distal segments remained inconspicuous for up to 3 months. PMID- 3104555 TI - Postoperative nutritional support in oral and maxillofacial surgery. AB - The patient sustaining maxillofacial trauma, disease or deformity presents with unique nutritional problems, especially during the postoperative period. By providing a nutritionally adequate diet in the preoperative and immediate postoperative period and during convalescence, complications can be reduced and healing improved. This paper details the nutritional requirements for patients and the indications for, and complications from, total parenteral nutrition and enteral nutritional support. PMID- 3104554 TI - Variability of arterial PO2 in hospitalized patients: implications for clinical practice and research. AB - The effects of position and ventilation on variability of PO2 in hospitalized patients were studied using a cross-over design. Arterial blood gases were obtained for 51 patients while they were lying and while they were sitting, and after five deep breaths (lying). The PO2 generally increased after five deep breaths but was not systematically changed by sitting up. Nineteen patients (37%) had changes in PO2 greater than or equal to 10 mm Hg. The patient's mean PO2 and respiratory rate influenced these differences. Among patients with a mean PO2 less than 85 mm Hg whose respiratory rates were greater than 20/min, only 11% had a change in PO2 greater than or equal to 10 mm Hg. In contrast, among patients with a mean PO2 greater than 85 mm Hg and a respiratory rate less than 20/min, 60% had a change in PO2 greater than or equal to 10 mm Hg. Considerable variability in PO2 is introduced by commonly encountered changes in position and ventilation. These conditions must be standardized when serial blood gas results are used to assess changes in a patient's condition. PMID- 3104556 TI - Ultrastructural and histochemical observations on intracellular and luminal microcalculi in the feline sublingual salivary gland. AB - As the genesis of salivary calculi in man has not been established, the fortuitous observation of microcalculi in sublingual glands of cats prompted this study. Microcalculi were seen occasionally within acinar cells and lumina and macrophages, and rarely interstitially. Microcalculi were stained with the periodic-acid/Schiff technique, and acid-phosphatase activity was associated with intracellular microcalculi. Intracellular microcalculi were seen ultrastructurally in acinar cells in membrane-bound vacuoles that also contained debris and sometimes what appeared to be secretory material. X-ray microanalysis showed the microcalculi to consist of crystals containing calcium and phosphorus. The observations suggest that the microcalculi form within autophagosomes in acinar cells by a precipitation of calcium and phosphorus present in degenerate material, and that the microcalculi eventually enter lumina, where they may be discharged in the saliva or retained and enlarge. PMID- 3104557 TI - Signet-ring cell microfollicular adenoma arising in a nodular ectopic thyroid. A case report. AB - A symptomless submandibular mass removed from a 61-year-old white male proved to be a signet-ring microfollicular adenoma arising in ectopic thyroid tissue. The lesion was established as a primary, non-mucin producing thyroid adenoma and a diagnosis of secondary signet-ring adenocarcinoma excluded. PMID- 3104558 TI - Immunoglobulin-producing cells in labial salivary glands of patients with rheumatoid arthritis and systemic lupus erythematosus. AB - The distribution of immunoglobulin-producing cells within labial salivary glands from normal individuals (n = 7) and patients with rheumatoid arthritis (n = 10) and systemic lupus erythematosus (n = 9) was studied using morphometric and indirect immunoperoxidase methods. Cell counts revealed a significant increase in the density of IgG cells within glands from both patient groups compared with glands from normal individuals. No significant differences in the density of IgA- or IgM-producing cells between the 3 groups were observed although large individual variations were apparent. Histomorphometric studies showed an increase in the lymphoid compartment and a decrease in glandular elements within glands from the 2 patient groups. When data for all specimens were pooled a significant positive correlation was obtained between the percent area of stromal lymphoid tissue and density of IgG and IgM cells. PMID- 3104559 TI - Analysis of HLA antigens in Japanese with oral lichen planus. AB - Analysis of HLA antigens was performed in 42 Japanese patients with oral lichen planus (OLP). There were no significant differences in the frequency of HLA-A, B, C antigens between OLP-patients and control subjects, although a decreasing trend in the frequency of Bw 52 and an increasing trend in that of Bw 61 and Cw 3 was noted. Among the HLA-DR and DQ antigens studied, the frequency of DRw 9 was significantly increased (Pc less than 0.05, RR = 3.3) and the relative risk was increased (RR = 6.0) when DRw 9 was carried on as a Bw 61/DRw 9 haplotype. Our results suggest that HLA-associated genetic factors play a role to some extent in the development of OLP. PMID- 3104560 TI - Dental and craniofacial anomalies of Axenfeld-Rieger syndrome. AB - Apart from the three distinguishing findings for the diagnosis of Axenfeld-Rieger syndrome (oligodontia, failure of periumbilical skin to involute, and ocular anterior chamber defects), a common feature is midface hypoplasia. Two theories have been proposed to explain the midface hypoplasia. One theory suggests a pleiotropic gene effect of defective neural crest cells, while the other theory proposes that midface hypoplasia is a local effect due to the absence of teeth. This study presents an evaluation of the craniofacial defects in a family affected with Axenfeld-Rieger syndrome. The maxillary deficiency in three affected patients was not limited to the alveolar regions. We conclude that a combination of skeletal and dentoalveolar factors contributes to the midface hypoplasia associated with Axenfeld-Rieger syndrome. PMID- 3104561 TI - The reversibility of the snuff-induced lesion: an experimental study in the rat. AB - Snuff lesions were induced in 30 rats. Ten of the snuff-exposed rats were killed immediately after 13 months snuff exposure, as were the 10 control animals. Ten rats were killed 1 month and 10 rats 4 months after the snuff administration had ceased. The rats exposed to snuff for 13 months exhibited hyperplastic, hyperorthokeratotic epithelium with focal mild atypia, focal ulcerations and marked subepithelial fibrosis. These changes were markedly reduced or absent in rats exposed to snuff and killed after a snuff-free interval of 1 or 4 months. Similar differences between the test-groups were seen in the epithelium lining the gingival sulcus of the lower incisors. This area seems to be more sensitive to chemical exposure than the oral mucosa proper as more severe microscopical changes were seen here. Snuff exposure results in the development of a hyperplastic, reactive, reversible lesion of the oral mucosa, suggesting that snuff predominantly has promoting activity when administered for a relatively short interval of time. PMID- 3104562 TI - Cells infiltrating human periapical inflammatory lesions. AB - Cells infiltrating human periapical granulomas and cysts were analyzed using cell suspensions. Over 50% of the total cells studied were lymphocytes whilst neutrophils were the next most frequent cell type observed. Two percent of the cells were mast cells. Only a few monocytes/macrophages and natural killer cells were found. More than half of the lymphocytes infiltrating the lesions were T cells, and more than half of the T cells were of the suppressor/cytotoxic (OKT8) phenotype. The OKT4/OKT8 ratio was 0.5. The findings are compared to previous reports and the differences discussed. PMID- 3104563 TI - The distribution of blood group antigens in experimentally produced carcinomas of rat palate. AB - It has been shown previously that rat oral epithelia express antigens cross reacting with antibodies against human blood group antigen B and its structural precursor, the H antigen (Type 2 chain). In the present study we investigated the expression of these antigens in malignant changes in the rat palate induced by a chemical carcinogen (4NQO). The H antigen, normally expressed on spinous cells in rats, was absent in malignant epithelium, whereas staining for the B antigen, normally expressed on basal cells, was variable. These changes are equivalent to those seen in human squamous cell carcinomas. The blood group antigen staining pattern in experimentally produced verrucous carcinomas showed an almost normal blood group antigen expression. This may have diagnostic significance. Localized areas of hyperplastic palatal epithelium with slight dysplasia revealed loss of H antigen and the presence of B antigen in suprabasal strata equivalent to the pattern seen in human premalignant epithelium. We conclude from these findings, that the rat model is well suited to study changes in cell surface carbohydrates during chemical carcinogenesis. PMID- 3104564 TI - Benign lymphoid hyperplasia of the palate. AB - Seven patients with benign lymphoid hyperplasia of the palate are reported. Clinically, these lesions presented as painless non-ulcerated masses that were unilateral in 6 of the cases and bilateral in one. Microscopically, the lesions were characterized by a mixed lymphoid infiltrate, germinal centres and vascular channels with hyperplasia of endothelial cells. The patients were followed for 3 10 years subsequent to diagnosis. One patient had 2 sequential lesions on opposite sides of the palate. Another patient with lesions of both submandibular salivary glands in addition to the palate developed rheumatoid arthritis, xerophthalmia and serologic changes consistent with systemic autoimmune disease. To date, none of the patients developed signs and symptoms of lymphoma or leukemia. The etiology of these lesions is unknown. Their distinction from lymphoma of the palate, as well as their possible relationship to the benign lymphoepithelial lesion of palatal mucous glands, is discussed. PMID- 3104566 TI - Malignant lymphoma of the oral cavity: clinicopathologic analysis of 20 cases. AB - Twenty cases of malignant lymphomas (ML) of the oral cavity were reviewed in the light of recent histologic classification. They occurred in 12 male and 8 female patients, with the age range of 11-80 years (median 51 years of age). Eighty percent of patients were stages IE and IIE. Histologically, 15 cases (75%) were ordinary non-Hodgkin's lymphoma (NHL) with diffuse large cell type being the most common. The remaining 5 cases, undefinable by classification scheme for ordinary NHL, were designated as malignant histiocytosis of the oral cavity (3 cases) and peripheral T-cell lymphoma (2 cases), respectively. There were no cases of follicular lymphoma. The present cases comprised 45% of high grade, 40% of intermediate grade, and 15% of low grade malignancy. A follow-up study showed that the stage of diseage, histologic classification, and frequency of mitosis correlated well with survival. PMID- 3104565 TI - Immunoglobulin-producing cells in human odontogenic cysts. AB - Immunohistochemical staining of immunoglobulin-containing plasma cells was performed on odontogenic keratocysts, dental (periapical) and dentigerous cysts. IgG-containing plasma cells were the predominant species in all cyst types examined, with a much lower percentage of IgA- and few IgM-containing plasma cells. Statistically significant differences in the percentage contributions of IgG and IgA plasma cells were observed between the keratocyst and both the dental (periapical) and dentigerous cysts and for IgM between the keratocyst and dental (periapical) cyst. Intense extracellular staining was observed for IgG in all cyst types. PMID- 3104567 TI - Localization of the genes shaking-B, small optic lobes, sluggish-A, stoned and stress-sensitive-C to a well-defined region on the X-chromosome of Drosophila melanogaster. AB - Using deletion mapping and complementation tests, we have localized 5 behavioral mutations: shaking-B2, small optic lobesKS58, sluggish-AEE85, stonedts1, and stress-sensitive-C1 to 4 genetic complementation groups at the base of the X chromosome. Shaking-B2 is an allele of the lethal complementation group R-9-29 near band 19E3; small optic lobesKS58 and sluggish-AEE85 belong to adjacent complementation groups, between lethals W2 and A112 near band 19F4; and stonedts1 and stress-sensitive-C1 are both alleles of the 8P1 lethal complementation group between lethals 114 and 13E3 near bands 20B-C. PMID- 3104568 TI - Suppression of inherited muscle degeneration in a Drosophila mutant by mechanical and genetical immobilizations. AB - The aperC (abnormal proboscis extension reflex C) mutation of Drosophila causes the degeneration of a particular pair of head muscles involved in the proboscis extension. To define the mechanisms underlying the muscle degeneration, we studied the influence of use or disuse on the muscle degeneration by two kinds of immobilization experiments. In the first experiment, the rostrum was fixed onto the cranium and the extension of the proboscis was mechanically prevented. In the second experiment, we created an aperC aperA double mutant, genetically preventing proboscis extension with the aperA mutation. Both immobilizations suppressed the muscle degeneration in aperC mutant flies. PMID- 3104569 TI - Sequential calcium and phosphorus balance studies in preterm infants. AB - Forty-six infant boys less than 1500 g at birth and less than 32 weeks gestation were fed enterally from birth until day 47. Cohorts were given milk formula varying in calcium and phosphorus content: group A, calcium 45 mg/dL, phosphorus 33 mg/dL; group B, calcium 85 mg/dL, phosphorus 33 mg/dL; group C, calcium 125 mg/dL, phosphorus 33 mg/dL; group D, calcium 125 mg/dL, phosphorus 50 mg/dL; and group E, calcium 125 mg/dL, phosphorus 64 mg/dL. Three-day balance studies were begun at days 10, 20, 30, and 40. Calcium net absorption and retention were influenced by postnatal age and calcium intake. Calcium retention best approached intrauterine accretion rates in group C. Phosphorus was well absorbed irrespective of the calcium content of the milk. Phosphorus retention increased with increments in the calcium content of the milk. Increasing the phosphorus content of the milk (groups D and E) resulted in no overall change in calcium absorption and retention but some increments in phosphorus retention. PMID- 3104570 TI - Effects of hydrogen peroxide on oral carcinogenesis in hamsters. AB - The effects of twice weekly topical applications of hydrogen peroxide on the buccal epithelium of Syrian hamsters were studied. Animals were treated either with hydrogen peroxide alone, with hydrogen peroxide and the carcinogen 9, 10 dimethyl-1,2-benzanthracene (DMBA), or with DMBA alone. In animals treated with 30% H2O2 alone, histopathologic examination after 22 weeks revealed hyperkeratosis and hyperplasia in all animals with hyperchromatic cells and mild dysplasia in four of nine: no tumors were seen. In animals treated with DMBA alone, three of seven (43%) developed epidermoid carcinoma, while six of 11 (55%) of animals treated with DMBA plus 3% hydrogen peroxide and five of five (100%) of animals treated with DMBA plus 30% hydrogen peroxide (P = 0.054) developed carcinoma. Thus, hydrogen peroxide can, by itself, induce pathologic changes frequently associated with preneoplastic lesions; it may also augment carcinogenesis associated with DMBA. PMID- 3104571 TI - [Modification of the sensitivity of Pseudomonas aeruginosa ATCC 15442 to chloroxylenol in the presence of protamine]. PMID- 3104572 TI - Antitumor effect of human recombinant interferon-gamma and -beta against human osteosarcoma transplanted into nude mice. AB - The antitumor activity of recombinant human interferon-gamma (ReIFN-gamma) and recombinant human interferon-beta (ReIFN-beta) against human osteosarcoma G-292 cells was compared in vitro and in vivo. Both IFNs inhibited the growth of G-292 cells cultured in vitro and transplanted into nude mice in vivo. In in vivo experiment, both IFNs injected i.t. were more effective at inhibiting the growth of G-292 cells than systemic administration such as i.v., i.p. or s.c. In comparing the various routes of systemic administration of both IFNs, i.v. injection was slightly more effective. Both IFNs exhibited more significant growth inhibition when they were administered every day for 10 d, as compared with a single or intermittent administrations, suggesting that the antitumor activity of both IFNs was time-dependent. Significant difference was not detected in the in vivo antitumor activity between both IFNs when they were compared on the basis of their antiviral units. However, the time dependency for antitumor effect of ReIFN-beta was more significant than that of ReIFN-gamma. ReIFN-gamma and ReIFN-beta used in combination exhibited synergistic antitumor activity both in vitro and in vivo, though the in vivo synergism of both IFNs was not so effective as that of in vitro: These results indicate that both ReIFN-gamma and ReIFN-beta are effective at inhibiting the growth of human osteosarcoma in vivo. PMID- 3104573 TI - Hyperalgesic action in mice of intracerebroventricularly administered arachidonic acid, PG E2, PG F2 alpha and PG D2: effects of analgesic drugs on hyperalgesia. AB - Hyperalgesic actions in mice of intracerebroventricularly (i.c.v.) administered arachidonic acid, prostaglandin (PG) E2, PG F2 alpha and PG D2 were studied. For the analgesic assay, the mouse tail pressure method was employed. The i.c.v. administration of arachidonic acid (0.01-100 micrograms/mouse), PG E2 (0.01-100 ng/mouse), PG F2 alpha (0.1-1000 ng/mouse) and PG D2 (0.1-1000 ng/mouse) decreased the pain threshold in a dose dependent manner. The doses that produced the maximal decrease in pain threshold for arachidonic acid, PG E2, PG F2 alpha and PG D2 were 10 micrograms/mouse, 10 ng/mouse, 100 ng/mouse and 100 ng/mouse, respectively. Acidic nonsteroidal antiinflammatory drugs (NSAIDs) produced much more potent analgesic effects in arachidonic acid-induced hyperalgesic mice than in normal mice and in PG E2-, PG F2 alpha- and PG D2-induced hyperalgesic mice, but nonacidic NSAIDs and morphine produced the same analgesic effect in both hyperalgesic and normal mice. Linoleic acid, linolenic acid and gamma-linolenic acid induced weak hyperalgesia, but this unsaturated fatty acids-induced hyperalgesia was not affected by indomethacin (2 mg/kg, p.o.). These findings indicate that the arachidonic acid and its metabolites were related to mediation or modulation of central pain pathways and that the central nervous system may be partially involved in the action of acidic NSAIDs. PMID- 3104575 TI - [Studies on the enhancing action of isoproterenol on the metabolism of mitomycin C]. PMID- 3104574 TI - Plasma levels of immunoreactive melatonin, estradiol, progesterone, follicle stimulating hormone, and beta-human chorionic gonadotropin during pregnancy and shortly after parturition in humans. AB - Plasma concentrations of immunoreactive melatonin, estradiol, progesterone, follicle stimulating hormone (FSH), and beta-human chorionic gonadotropin (beta hCG) were studied between 1000 and 1230 h in 105 Chinese females during six periods of normal pregnancy and 1-5 min after normal delivery. We have also examined the midday levels of immunoreactive melatonin in the cord blood of fetuses and plasma collected 1-5 min after and 24 h after delivery from their mothers. Concentrations of hormone immunoreactivities were determined by radioimmunoassay, and distinct fluctuations of all hormones were recorded during pregnancy. In the pregnant females, there were significant negative correlations between melatonin and estradiol, melatonin and progesterone, beta hCG and progesterone, and beta hCG and estradiol, and positive correlations between melatonin and FSH and progesterone and estradiol. Furthermore, plasma melatonin levels in the cord blood demonstrated no sex difference and were significantly lower than and correlated positively with the levels in their mothers. Our results suggest that sex steroids may inhibit and FSH may potentiate circulating melatonin levels in gravid women; changes in the levels of melatonin during pregnancy may affect the in utero development of the human embryo; and circulating melatonin in the mother may be the major source of blood melatonin in the fetus before parturition. PMID- 3104576 TI - Target organ directed drug delivery: evaluation of renal infusion of chromium-51 ethylenediaminetetraacetate and sodium o-[125I]iodohippurate in the Wistar Kyoto rat. AB - To evaluate the merits of intrarenal drug delivery, the disposition of chromium 51 ethylenediaminetetraacetate (51Cr EDTA) and sodium o-[125I]iodohippurate (125I OIH) was studied following their constant-rate infusion into either the jugular vein or the left or right renal artery of Wistar Kyoto rats. The contralateral kidney was removed. Renal blood flow through the lateral kidney was measured during the experiment via an electromagnetic flow probe. Urine and systemic arterial blood samples were taken at steady state. The clearance and extraction of both substances by the right kidney were independent of the route of administration. Nonlinear kinetics were observed during infusion of 125I OIH at the highest infusion rate in the left kidney. At steady state the advantage of intrarenal over systemic delivery was limited because of the relative high blood flow of the kidney. Only a small reduction (30%) in systemic concentration was achieved by infusion of 51Cr EDTA. Intrarenal infusion of the lower dose (10 nCi/min) of 125I OIH reduced the systemic concentration by greater than 80% when compared with systemic infusion. Intrarenal infusion of the higher dose (40 nCi/min) saturated elimination processes in parts of the left kidney because of nonhomogeneous flow distribution. PMID- 3104577 TI - Characterization of liposomes and an emulsion containing mitomycin C or lipophilic mitomycin C prodrugs. AB - The characteristics of liposomes and an oil-water emulsion containing either mitomycin C (MMC) or its lipophilic prodrugs were investigated. Prodrugs were incorporated into liposomes and oil droplets of an oil-water emulsion, and this incorporation was dependent on the lipid content of the liposomes and droplets. A good correlation was observed between the calculated lipid:water partition ratios and partition coefficients in chloroform:water. The prodrugs were rapidly distributed between the lipid and aqueous phases when they were injected into the dispersion medium of empty liposomes and an oil-water emulsion, or when the formulations incorporating prodrugs were diluted with water. Addition of prodrugs to liposomes containing perylene resulted in a decrease of fluorescence. Based on these findings, prodrugs were concluded to be incorporated into lipidic dispersion formulations based on their partitioning behavior. N1a [(Nonyloxy)carbonyl]MMC (7) showed the highest incorporation into lipidic formulations, while prodrugs with moderate lipophilicities were rapidly released from lipid particles. Liposomes incorporating 7 maintained their multilamellar vesicular form as shown by electron microscopy and by examining their entrapping capacity for water soluble marker dyes. The release of prodrug 7 from both formulations was slow in a buffer solution, but considerable release and conversion to the parent drug were observed when rat plasma was added to the same system. These results suggest that the stability of MMC could be improved by incorporation into lipidic formulations and that a suitable release rate in vivo could be accomplished by use of a prodrug. PMID- 3104578 TI - Gabexate mesylate inhibition of serine proteases: thermodynamic and computer graphics analysis. AB - The inhibitory effect of gabexate mesylate, which is used therapeutically in the treatment of pancreatitis and disseminated intravascular coagulation, and as a regional anticoagulant agent for hemodialysis, has been measured on bovine factor Xa, bovine alpha-thrombin, human Lys77-plasmin, human urinary kallikrein, human urokinase, porcine pancreatic beta-kallikrein-B, and bovine beta-trypsin catalyzed hydrolysis of p-nitrophenyl esters of N-alpha-carbobenzoxy-L-arginine and N-alpha-carbobenzoxy-L-lysine. On the basis of enzyme:gabexate mesylate affinities, the serine proteases can be arranged as follows: human urinary kallikrein approximately porcine pancreatic beta-kallikrein-B much less than bovine beta-trypsin approximately bovine factor Xa approximately human Lys77 plasmin approximately human urokinase approximately bovine alpha-thrombin. The mode of binding of gabexate mesylate to the serine proteases conforms to the active-reactive site geometries observed in their complexes with natural and synthetic inhibitors. Differences in gabexate mesylate affinities for these proteases reflect structural differences at their primary specificity subsite, which have been investigated by comparative analysis of amino acid sequences and by computer-graphics techniques. PMID- 3104579 TI - Synthesis and antimicrobial activities of N4-(2 acetoxyethoxymethyl)thiosemicarbazones and N3-(2-acetoxyethoxymethyl)thioureas. AB - A series of thiosemicarbazones and thioureas having an open-chain analogue of the ribosyl group, the 2-acetoxyethoxymethyl moiety, has been synthesized. Significant growth inhibitory activity versus gram-positive and gram-negative organisms, a yeast, and a mold has been found with the 2-acetoxyethoxymethyl derivatives of N-alkyl-, aryl-, and heteroaryl-thiosemicarbazones and thioureas. The molecules may function as inhibitors of ribonucleotide reductase or in utilization of the carbamyl group in pyrimidine biosynthesis. PMID- 3104580 TI - Antibacterial activity of 6,8-disubstituted-quinolone-3-carboxylic acids. AB - Twelve 6,8-disubstituted-1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid derivatives were prepared and evaluated for their antibacterial activity. Among these, only the 6,8-difluoroquinolinone-3-carboxylic acid showed moderate activity. PMID- 3104581 TI - Calcium ionophore (A23187)- and arachidonic acid-stimulated prostaglandin release from microvascular endothelial cells: effects of calcium antagonists and calmodulin inhibitors. AB - Calcium ionophore (A23187)-stimulated prostaglandin (PG) E2 and I2 (measured as 6 keto PGF1 alpha) release from cultured rabbit coronary microvessel endothelial (RCME) cells in a time- and dose-dependent manner. A23187-stimulated PG release was reduced by the calcium channel blockers nifedipine, verapamil and diltiazem and by the intracellular calcium blocker, 8-(diethylamino)-octyl-3,4,5 trimethoxybenzoate. A23187-stimulated PG release was significantly reduced by lowering the calcium concentration in the buffer to concentrations of 0.2 mM or less. A23187-stimulated 45Ca uptake was not inhibited by nifedipine (0.5 microM), diltiazem (10 micron) or verapamil (50 microM) although these same concentrations of calcium channel blockers significantly inhibited A23187-stimulated PG release. However, these concentrations of calcium blockers did inhibit K+ (10 mM) valinomycin (5 microM)-stimulated 45Ca uptake, indicating that, although RCME cells probably have voltage-dependent calcium channels and although calcium influx via these channels is blocked by the calcium channel blockers, voltage dependent calcium influx plays little or no role in A23187-stimulated 45Ca influx and PG release. KCl-valinomycin significantly stimulated PG release, but this increase was not significantly affected by either nifedipine (0.5 microM) or diltiazem (10 microM) despite complete inhibition of KCl-valinomycin-stimulated 45Ca influx. Verapamil (50 microM) exhibited a small but significant suppression of KCl-valinomycin-stimulated PG release. These observations most likely indicate that calcium influx by voltage-dependent calcium channels plays little or no role in the events leading to either A23187- or KCl-valinomycin-stimulated PG release. The calmodulin antagonists, trifluoperazine and calmidazolium, also reduced A23187-stimulated PG release. In vitro studies of porcine pancreatic phospholipase (PL) A2 activity suggested that the inhibitory actions of trifluoperazine, but not the calcium antagonists, may be mediated by direct inhibitory actions on PLA2. Studies with [3H]arachidonic acid (AA)- and [14C]stearic acid-prelabeled RCME cells suggested that A23187 stimulated both PLA2 and PLC activity, leading to the release of AA. Studies with exogenous AA indicated that reducing calcium availability by reducing buffer calcium concentrations resulted in an enhanced conversion of exogenous AA to PGs. RCME cells incubated in nominally calcium-free buffer exhibited a decreased rate of AA incorporation. The observed increase in AA conversion to PGs in low calcium buffer suggests that calcium may stimulate AA uptake and acylation as well as AA release.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3104582 TI - Arachidonic acid-induced endothelial-dependent relaxations of canine coronary arteries: contribution of a cytochrome P-450-dependent pathway. AB - Arachidonic acid (AA, 10(-8)-5 X 10(-6) M) induced dose-dependent relaxations of canine coronary arterial rings precontracted with dinoprost that were significantly greater (P less than .001) if the endothelium was intact. Cyclooxygenase inhibition with indomethacin displaced the dose-response curve to AA to the right but did not prevent the relaxant effects of the fatty acid. SKF 525A, an inhibitor of cytochrome P-450-dependent enzymes, also attenuated the response to AA although the combination of SKF-525A and indomethacin prevented any relaxant effect. Induction of cytochrome P-450-dependent enzymes in the coronary artery with 3-methylcholanthrene and beta-naphthoflavone given in vivo (40 mg/kg/day for 3 days) or depletion of these enzymes with cobalt chloride (24 mg/kg/day for 2 days) resulted in an enhancement or diminution, respectively, of AA-induced endothelial-dependent relaxations. These results implicate a cytochrome P-450-dependent mixed function oxidase in the endothelial-dependent relaxations to AA in the canine coronary artery. Precontraction of coronary arteries with U46619 in contrast to dinoprost failed to display endothelial dependent relaxations to AA, whereas the responses to bradykinin and acetylcholine were also partially attenuated. Pharmacologic manipulations of AA metabolism via cyclooxygenase and cytochrome P-450-dependent monooxygenases indicate that the endothelial-dependent relaxations induced by bradykinin are partially dependent upon metabolites of AA, whereas the relaxations produced by acetylcholine are independent of AA metabolites, suggesting that a number of potential relaxing factors may be released from the endothelium. PMID- 3104584 TI - Smear removal agents: a quantitative study in vivo and in vitro. PMID- 3104585 TI - Adenocarcinoma complicating a duodenal diverticulum. PMID- 3104583 TI - Ionic regulation of sea urchin sperm motility, metabolism and fertilizing capacity. AB - In order to pursue the significance of the ionic regulation of sea urchin sperm behaviour, alterations in the cation composition of sea water were tested for their effects on sperm fertilizing capacity. Nearly all changes which resulted in lowered sperm intracellular pH, including lowered sea-water pH, inclusion of the divalent ion chelator EGTA, addition of dithiothreitol, or removal of sea-water Na+, enhanced sperm viability for periods of up to a week. These conditions caused decreased cell motility and elevated ATP concentrations, and prevented the acrosome reaction. Conversely, changes which increased the intracellular pH, decreased sperm ATP concentrations, or induced the acrosome reaction, reduced sperm viability. A single medium, high sea-water K+ concentrations (greater than 100 mM), provided an exception to these general trends. At elevated K+ concentrations sperm were quiescent but became completely infertile. These data show that sperm fertilizing capacity is generally extended by maintenance of the sperm in an inactive state, and the results suggest that decreased cellular energy levels contribute to decreased fertility. PMID- 3104586 TI - Absence of HLA linkage in familial hypogonadotropic hypogonadism. AB - In a family with five daughters, three suffered from primary amenorrhea. The diagnosis of familial idiopathic gonadotropin deficiency (FIGD) was established. The entire family underwent HLA evaluation, and no linkage between the HLA and FIGD was found. PMID- 3104587 TI - Sex hormone status in women suffering from rheumatoid arthritis. AB - We studied the sex hormone status of 21 seropositive (IgM-RF) women with rheumatoid arthritis (RA), who were subdivided according to their premenopausal and postmenopausal status. Age matched women with secondary osteoarthritis were used as controls. The hormones evaluated were luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), 17-beta-estradiol (E2), progesterone (Pg), testosterone (T), delta 4-androstenedione (A), dehydrotestosterone (DHT), dehydroepiandrosterone sulphate (DHEAS) and cortisol (C). Normal concentrations of all the hormones considered were found in premenopausal women with RA. Statistically higher concentrations of T (p less than 0.05), A (p less than 0.05) and DHEAS (p less than 0.01) were observed in postmenopausal women with RA when compared to controls, whereas no differences were found for all other hormones studied. Although the significance of observed relative hyperandrogenism in postmenopausal women with RA is not clear, our data seem to indicate that sex hormone levels are altered in patients with RA. PMID- 3104588 TI - Growth hormone releasing factors. PMID- 3104589 TI - Benzimidazole derivatives with atypical antiinflammatory activity. AB - A number of substituted 2-[(2,2,2-trifluoroethyl)sulfonyl]-1H-benzimidazoles (4) have demonstrated antiinflammatory activity that appears to have a mechanism distinct from typical cyclooxygenase inhibiting nonsteroidal antiinflammatory drugs. Several of these compounds inhibit adjuvant-induced arthritis in rats at 25 mg/kg while showing no activity in the carrageenan paw edema model at up to 100 mg/kg. Two compounds, 4a and 4b, showed no significant inhibition of cyclooxygenase in vitro at concentrations as high as 5 X 10(-5) M. All compounds 4 active in adjuvant-induced arthritis were also found to inhibit release of lysosomal enzymes from neutrophils, raising the possibility that their antiinflammatory effect is at least partially mediated by an effect on neutrophil function. PMID- 3104590 TI - An oculocerebral hypopigmentation syndrome: a case report with clinical, histochemical, and ultrastructural findings. AB - A 4 year old boy is reported with tyrosinase positive hypopigmentation, mental retardation, ataxia, and myopia. Radiological investigation showed occipital cerebral atrophy, coxa valga, and generalised osteoporosis. The skin histology and electron microscopy are reported and discussed. The clinical features are similar to those of the oculocerebral hypopigmentation syndrome described by Preus et al. PMID- 3104591 TI - Penicillin-binding proteins in Streptococcus faecalis and S. faecium. AB - Penicillin-binding proteins (PBPs) of Streptococcus faecalis NCTC 775, S. faecium NCTC 7171 and an isolate of S. faecium (strain 37) highly resistant to beta lactam antibiotics were visualised by autoradiography. Five PBPs were detected in S. faecalis NCTC 775 and six in S. faecium NCTC 7171. Additional PBPs could not be found in the resistant isolate of S. faecium. The PBP affinities of beta lactams were compared with MIC values. The affinities of PBPs 3 and 4 of S. faecalis NCTC 775 for penicillin G, ampicillin, cefathiamidine, cephaloridine and cephazolin were related to the sensitivity of the strain to these antibiotics as were the affinities of PBPs 4 and 5 in each S. faecium strain for the beta lactams. It is postulated that PBPs 3 and 4 of S. faecalis NCTC 775 and PBPs 4 and 5 of S. faecium are the relevant target enzymes of the test antibiotics. PBPs 4 and 5 of the highly beta-lactam-resistant S. faecium strain 37 showed proportionally low affinities for the five beta lactams compared to that of the less resistant strain S. faecium NCTC 7171. Decreased affinities of PBPs 4 and 5 may account for the resistance in S. faecium strain 37 to beta lactams. The affinities for PBP 1, 2 and 5 in S. faecalis NCTC 775 and PBPs 1, 2, 3 and 6 in S. faecium were not related to the antibiotic sensitivities. PMID- 3104592 TI - Purification of cytotoxic enterotoxin of Aeromonas sobria by use of monoclonal antibodies. AB - Cytotoxic enterotoxin of Aeromonas sobria was purified by affinity chromatography with monoclonal antibodies. The purified enterotoxin gave a single protein band in polyacrylamide gradient gel electrophoresis and its mol. wt estimated by this technique was 63,000; it had a pI of 6.2. The purified enterotoxin caused fluid accumulation in rat ileal loops and in infant mice, was cytotoxic to cultured cells, was haemolytic to human erythrocytes, and was lethal to mice after intravenous injection. The relative concentrations of enterotoxic, cytotoxic and haemolytic activities were approximately the same in a culture filtrate and in purified, electrophoretically homogeneous enterotoxin. The three activities were also inactivated to the same extent after incubation for 10 min at 56 degrees C. There was no immunological cross-reactivity with cholera toxin (CT) nor did antiserum to CT neutralise the biological effects of the toxin. PMID- 3104593 TI - Identification and quantification of a monoclonal IgM euglobulin: pitfalls and methodologic instruction. AB - In a patient with Waldenstrom's macroglobulinemia routine agarose gel electrophoresis and immunofixation disclosed an IgM-kappa M-component with beta mobility, but failed to unveil a major monoclonal IgM-kappa euglobulin. This, however, was demonstrated when the procedures were performed in a buffer with NaCl-ion-strength of 0.1 M. Similarly, IgM quantification by routine nephelometry and electroimmunoassay led to dramatically inconsistent results. By a simple agarose gel electrophoresis in NaCl 0.1 M the IgM euglobulin was quantified proportional to the serum concentration of albumin. The identification and classification of an M-component, being exceedingly important diagnostically, may be missed, when solely routine electrophoresis and immunofixation is employed. As regards the quantification of M-components, these are not merely pathologic immunoglobulins nosologically. Also, biochemically they differ from normal, polyclonal immunoglobulins, resulting in immunological techniques being inapplicable for their quantification. For quantitative purposes, a simple, comparative agarose gel electrophoresis is described. PMID- 3104594 TI - Evaluation of different preparations of aggregated human IgG for use as a standard in the assays of circulating immune complexes. AB - Comparative studies were carried out with regards to different preparations of aggregated human IgG (AGHG) to be used as the standard protein in the assays to estimate the amounts of circulating immune complexes. 5 different preparations of AGHG were used, in which WHO reference AGHG and glutaraldehyde-polymerized AGHG were included. These AGHG preparations were measured by the 4 different binding assays. Glutaraldehyde-polymerized AGHG, though weaker than heat-denatured AGHG in the binding activities, showed apparent dose-dependent curves in the 4 assays. It was also shown that molecular size of AGHG affect the binding activities: the smaller the molecular size, the weaker the binding activities. These results are considered to provide invaluable information for the standardization of the preparation of AGHG. PMID- 3104595 TI - The effect of corticosteroids and other antineoplastic agents on the generation of leukocyte migration inhibition factor. AB - We have shown that hydrocortisone in physiological concentrations can inhibit the production of leukocyte migration inhibition factor (LMIF), but does not diminish the action of this lymphokine. Other agents tested failed to influence LMIF production. Inhibition of LMIF production by corticosteroids was influenced by the nature of the stimulus used for the production as an effect could be seen with PHA or Con A, but not Staphylococcal enterotoxin A (SEA). Production of LMIF was promptly restored after removal of the steroids. Furthermore, addition of a calcium ionophore to PHA restored the production of LMIF even in the presence of corticosteroids. In contrast, addition of exogenous IL-2 did not correct the defect in lymphokine secretion. We believe that inhibition of the production of LMIF by steroid may lead to defective granulocytic function and thus, predispose to infection. PMID- 3104596 TI - Immunoglobulin isotypes in the circulating immune complexes of diabetic rats with and without proteinuria: a chronological study. AB - Circulating immune complexes (CIC) have been postulated to contribute to the development of the secondary complications of diabetes mellitus. Therefore studies were performed to determine whether CIC are the cause of the consequence of the development of diabetic nephropathy. This was done by comparing the occurrence and concentration of CIC containing the different isotypes of immunoglobulins in control rats to those detected in streptozotocin-induced (Sz) diabetic rats that developed albuminuria (Group I) and that did not develop albuminuria (Group II). Only CIC containing IgM, IgG2b and IgG2c were detected in diabetic rats. By staging Group I albuminuric diabetic rats to a clinical reference point of albuminuria, there was no correlation between the occurrence or concentration of CIC containing any isotype of immunoglobulin and the onset of albuminuria. In all Group I albuminuric diabetic rats, the occurrences of all CIC were variable and their concentrations fluctuated during the development and early progression of nephropathy. However, after this group of diabetic rats progressed to overt nephropathy (marked by albuminuria and IgG proteinuria), CIC could be demonstrated in 100% of the animals. In diabetic rats that did not develop albuminuria (Group II), CIC containing IgG2b occurred earlier and more often than in Group I albuminuric rats. Similarly, the subclass IgG2c was detected in the CIC of Group II non-albuminuric rats more frequently and in higher concentrations than in Group I albuminuric rats. CIC containing IgM were detected in all 3 animal groups, however, in higher concentrations and occurrences in Group II non-albuminuric rats as compared to control and Group I albuminuric rats. The consistent elevation in CIC after the development of diabetic nephropathy, suggests that the CIC containing any immunoglobulin isotype either result from diabetic kidney, or from other deteriorating conditions associated with the diabetic state. The data also suggests that CIC are not involved in the onset or progression of diabetic nephropathy regardless of the isotypes of immunoglobulins contained within the CIC. However, there is an isotypic restriction in the immunoglobulins detected in the CIC of diabetic rats (IgM, IgG2b and IgG2c) that may signal some involvement of the immune system in the development of diabetic nephropathy. PMID- 3104597 TI - Membrane potentials and intracellular Cl- activity of toad skin epithelium in relation to activation and deactivation of the transepithelial Cl- conductance. AB - The potential dependence of unidirectional 36Cl fluxes through toad skin revealed activation of a conductive pathway in the physiological region of transepithelial potentials. Activation of the conductance was dependent on the presence of Cl or Br in the external bathing solution, but was independent of whether the external bath was NaCl-Ringer's, NaCl-Ringer's with amiloride, KCl-Ringer's or choline Cl Ringer's. To partition the routes of the conductive Cl- ion flow, we measured in the isolated epithelium with double-barrelled microelectrodes apical membrane potential. Va, and intracellular Cl- activity, acCl, of the principal cells identified by differential interference contrast microscopy. Under short-circuit conditions, Isc = 27.0 +/- 2.0 microA/cm2, with NaCl-Ringer's bathing both surfaces, Va was -67.9 +/- 3.8 mV (mean +/- SE, n = 24, six preparations) and acCl was 18.0 +/- 0.9 mM in skins from animals adapted to distilled water. Both Va and acCl were found to be positively correlated with Isc (r = 0.66 and r = 0.70, respectively). In eight epithelia from animals adapted to dry milieu/tap water Va and acCl were measured with KCl Ringer's on the outside during activation and deactivation of the transepithelial Cl- conductance (GCl) by voltage clamping the transepithelial potential (V) at 40 mV (mucosa positive) and -100 mV. At V = 40 mV; i.e. when GCl was deactivated, Va was -70.1 +/- 5.0 mV (n = 15, eight preparations) and acCl was 40.0 +/- 3.8 mM. The fractional apical membrane resistance (fRa) was 0.69 +/- 0.03. Clamping to V = -100 mV led to an instantaneous change of Va to 31.3 +/- 5.6 mV (cell interior positive with respect to the mucosal bath), whereas neither acCl nor fRa changed significantly within a 2 to 5-min period during which GCl increased by 1.19 +/- 0.10 mS/cm2. When V was stepped back to 40 mV, Va instantaneously shifted to -67.8 +/- 3.9 mV while acCl and fRa remained constant during deactivation of GCl. Similar results were obtained in epithelia impaled from the serosal side. In 12 skins from animals adapted to either tap water or distilled water the density of mitochondria-rich (DMRC) cells was estimated and correlated with the Cl current (ICl through the fully activated (V = -100 mV) Cl conductance). A highly significant correlation ws revealed (r = -0.96) with a slope of -2.6 nA/m.r. (mitochondria-rich cell and an I-axis intercept not significantly different from zero.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3104598 TI - Nucleotide sequences that define promoters that are used by Bacillus subtilis sigma-29 RNA polymerase. AB - There are at least five different forms of RNA polymerase holoenzyme in Bacillus subtilis. These enzymes differ in their sigma subunit and their specificity for promoter utilization. One form of RNA polymerase (E sigma 29) that contains a 29,000 Mr sigma appears in B. subtilis about two hours after the initiation of endospore formation. The determination of the nucleotide sequences that govern utilization of promoters by E sigma 29 has been limited by the small number of cloned promoters that are recognized by E sigma 29. We have determined the nucleotide sequence of a recently isolated promoter (G4) that is used exclusively by E sigma 29 both in vitro and in vivo. The start-point of transcription was identified by S1 nuclease mapping and dinucleotide priming experiments and the probable promoter element was sequenced. We compared the sequence with that of six promoters that are used to varying degrees in vitro by E sigma 29 and found these sequences to be highly conserved at the -10 and near the -35 regions of these promoters. Single base substitutions were generated at positions -12, -15 and -36 of the G4 promoter and assayed for their influence on utilization by E sigma 29 in in-vitro competition experiments. The effects of these mutations in G4 on its use by E sigma 29 support a model in which E sigma 29 utilizes its cognate promoters by interacting with unique nucleotide sequences at the -10 region and near the -35 region of these promoters. PMID- 3104599 TI - Template-directed synthesis on short oligoribocytidylates. AB - The oligonucleotides C(pC)n, n = 4, 5, 6, 7, are efficient templates for the oligomerization of guanosine-5'-phospho-2-methylimidazole (2-MeImpG). They yield oligomeric products that are substantially less regiospecific than those obtained on polycytidylate [poly(C)]. The overall distributions of products obtained on oligo(C)s are generally similar to those of products obtained on oligodeoxycytidylates [oligo(dC)s], but there are substantial differences in the ratios of isomers. The 3'-5'-linked dinucleoside monophosphate GpG efficiently initiates oligomer formation with 2-MeImpG on oligo(C) templates. The pattern of products obtained by chain extension parallels closely that of products obtained directly from 2-MeImpG, except that the former products lack the 5'-terminal phosphate group. PMID- 3104600 TI - Abiogenic synthesis of oligonucleotides on kaolinite under the action of ultraviolet radiation. AB - The present work deals with the processes involved in the abiogenic polycondensation of nucleotides adsorbed on the clay mineral kaolinite under the action of ultraviolet (UV) radiation. The dependence of the yield of synthesis products on irradiation dose was studied. The maximum yield corresponds to a 6-h exposure. The newly synthesized substances were analyzed by ion-exchange chromatography. Some fractions were studied for the type of bonds they contained by venom phosphodiesterase and RNase T2 enzymatic hydrolysis. It was determined that some of the products synthesized by exposure of AMP adsorbed on the surface of clay particles to UV radiation may be looked upon as oligonucleotides in which some fragments have 2'-5'-bonded and others 3'-5'-bonded nucleotides. PMID- 3104601 TI - Molecular evolution of the carbonic anhydrase genes: calculation of divergence time for mouse carbonic anhydrase I and II. AB - A cDNA clone in pBR322 that cross-hybridizes with a mouse carbonic anhydrase form II (CAII) probe has been sequenced and identified as mouse carbonic anhydrase form I (CAI). The 1224-base-pair clone encodes the entire 260-amino-acid protein and appears to contain an Alu-like element in the 3' untranslated region. The deduced amino acid sequence exhibits 77% homology to human CAI and contains 17 of the 20 residues that are considered unique to and invariant for all mammalian CAI isozymes. The results of a detailed comparison of the nucleic acid sequences spanning the coding regions of mouse CAI and rabbit CAI have been used to calibrate an evolutionary clock for the carbonic anhydrases (CAs). These data have been applied to a comparison of the mouse CAI and CAII nucleic acid sequences to calculate the divergence time between the two genes. The divergence time calculation provides the first estimation of the evolutionary relationship between CAs based entirely on nucleotide sequence comparison. PMID- 3104602 TI - Nucleotide sequences of Cyanophora paradoxa cellular and cyanelle-associated 5S ribosomal RNAs: the cyanelle as a potential intermediate in plastid evolution. AB - The 5S ribosomal RNAs from the cell cytoplasm and cyanelle (photosynthetic organelle) of Cyanophora paradoxa have been isolated and sequenced. The cellular and cyanelle 5S rRNAs were 119 and 118 nucleotides in length, respectively. Both RNAs exhibited typical 5S secondary structure, but the primary sequence of the cellular species was clearly eukaryotic in nature, while that of the organellar species was prokaryotelike. The primary sequence of the cyanellar 5S rRNA was most homologous to cyanobacterial 5S sequences, yet possessed secondary structural features characteristic of higher-plant chloroplast 5S rRNAs. Both sequence comparison and structural analysis indicated an evolutionary position for cyanelle 5S rRNA intermediate between blue-green alga and chloroplast 5S rRNAs. PMID- 3104603 TI - Characterization of the two nonallelic genes encoding mouse preproinsulin. AB - We have cloned and sequenced the two mouse preproinsulin genes. The deduced amino acid sequences of the mature mouse insulins are identical to the published protein sequences. However, the nucleotide sequence indicates that the mouse I C peptide has a deletion of two amino acids compared with the mouse II C-peptide. We used an S1 nuclease assay to confirm the presence of the deletion and to measure the ratio of transcripts from gene I to transcripts from gene II. The mouse preproinsulin I gene, like the rat gene I, is missing the second intervening sequence that normally interrupts the C-peptide region in other insulin genes. Comparison of the 5' flanking sequences of the mouse and rat genes II indicates that they are homologous for at least 1000 base pairs. The preproinsulin I genes also share homology in their 5' flanking DNAs; however, their homology to the preproinsulin II genes extends for only about 500 base pairs. PMID- 3104604 TI - Enzymatic synthesis and some properties of a model primitive tRNA. AB - A model primitive tRNA with the nucleotide sequence GGCCAAAAAAAGGCCp was synthesized using T4 RNA ligase. The nucleotide sequence of this newly synthesized oligonucleotide was confirmed by ladder analysis of several enzymatic digestion products. The secondary structure of the oligonucleotide was examined by comparison of the products of its digestion by single- and double-strand specific nucleases with those of the digestion of the intermediate oligonucleotide GGCCAAAAAAAOH. The results indicated that the two GGCC segments of the 5' and 3' ends of the model tRNA may form base pairs in solution. The same conclusion was derived from the result of affinity-column chromatography of the model oligonucleotide. When 32pGGCCAAAAAAAGGCCOH was passed through a poly(U) agarose column, about 70% of the applied sample bound to the poly(U)-agarose. In contrast, when the model oligonucleotide was passed through a poly(C)-agarose column, only 15% of the sample bound to the poly(C)-agarose. These results indicate that the newly synthesized oligonucleotide adopts a hairpin structure in solution. Two aspects of a potential biological activity of the synthetic model tRNA were examined. It was found that the oligonucleotide can bind to poly(U) programmed 30S ribosomes and is recognized by Q beta replicase as a template for RNA synthesis. PMID- 3104605 TI - The complete amino acid sequences of cytosolic and mitochondrial aspartate aminotransferases from horse heart, and inferences on evolution of the isoenzymes. AB - We report here the complete amino acid sequences of the cytosolic and mitochondrial aspartate aminotransferases from horse heart. The two sequences can be aligned so that 48.1% of the amino acid residues are identical. The sequences have been compared with those of the cytosolic isoenzymes from pig and chicken, the mitochondrial isoenzymes from pig, chicken, rat, and human, and the enzyme from Escherichia coli. The results suggest that the mammalian cytosolic and mitochondrial isoenzymes have evolved at equal and constant rates whereas the isoenzymes from chicken may have evolved somewhat more slowly. Based on the rate of evolution of the mammalian isoenzymes, the gene-duplication event that gave rise to cytosolic and mitochondrial aspartate aminotransferases is estimated to have occurred at least 10(9) years ago. The cytosolic and mitochondrial isoenzymes are equally related to the enzyme from E. coli; the prokaryotic and eukaryotic enzymes diverged from one another at least 1.3 X 10(9) years ago. PMID- 3104606 TI - Examination of protein sequence homologies: III. Ribosomal protein YS25 from Saccharomyces cerevisiae and its counterparts from Schizosaccharomyces pombe, rat liver, and Escherichia coli. AB - The sequences of the ribosomal proteins YS25, SP-S28, RL-S21, and Ec-S6, from Saccharomyces cerevisiae, Schizosaccharomyces pombe, rat liver, and Escherichia coli, respectively, have been examined using a computer program that searches for homologous tertiary structures. Matrices of comparisons among the eukaryotic sequences show that they match each other sequentially without any internal gaps. The average values of the correlation coefficients obtained from the comparison matrices are higher for the first halves of the sequences than for the latter halves. This result suggests that the first halves of the sequences may represent a more important domain than the latter halves. The comparison matrices between the eukaryotic and bacterial sequences of ribosomal proteins, however, do not show sequentially arranged homology, though there are six well-matching segments arranged in different orders in the two types of sequences. This implies that the eukaryotic sequences of the ribosomal protein were reconstituted by two internal transpositions and six deletions of 4-12 residues each from the ancestral sequence during the divergence between bacterial and eukaryotic genes. These findings may give insight into structural and quantitative studies of evolutionary divergence between eukaryotes and prokaryotes. PMID- 3104607 TI - Statistical properties of molecular tree construction methods under the neutral mutation model. AB - The statistical properties of three molecular tree construction methods--the unweighted pair-group arithmetic average clustering (UPG), Farris, and modified Farris methods--are examined under the neutral mutation model of evolution. The methods are compared for accuracy in construction of the topology and estimation of the branch lengths, using statistics of these two aspects. The distribution of the statistic concerning topological construction is shown to be as important as its mean and variance for the comparison. Of the three methods, the UPG method constructs the tree topology with the least variation. The modified Farris method, however, gives the best performance when the two aspects are considered simultaneously. It is also shown that a topology based on two genes is much more accurate than that based on one gene. There is a tendency to accept published molecular trees, but uncritical acceptance may lead one to spurious conclusions. It should always be kept in mind that a tree is a statistical result that is affected strongly by the stochastic error of nucleotide substitution and the error intrinsic to the tree construction method itself. PMID- 3104608 TI - Compositional constraints and genome evolution. AB - Nucleotide sequences of all genomes are subject to compositional constraints that affect, to about the same extent, both coding and noncoding sequences; influence not only the structure and function of the genome, but also those of transcripts and proteins; are the result of environmental pressures; and largely control the fixation of mutations. These findings indicate that noncoding sequences are associated with biological functions; that the organismal phenotype comprises two components, the classical phenotype, corresponding to the "gene products," and a "genome phenotype," which is defined by the compositional constraints; and that natural selection plays a more important role in genome evolution than do random events. PMID- 3104609 TI - Evolution of proteins in mammalian cytoplasmic and mitochondrial ribosomes. AB - The proteins of cytoplasmic and mitochondrial ribosomes from the cow and the rat were analyzed by co-electrophoresis in two dimensional polyacrylamide gels to determine their relative evolutionary rates. In a pairwise comparison of individual ribosomal proteins (r-proteins) from the cow and the rat, over 85% of the cytoplasmic r-proteins have conserved electrophoretic properties in this system, while only 15% of the proteins of mitochondrial ribosomes from these animals fell into this category. These values predict that mammalian mitochondrial r-proteins are evolving about 13 times more rapidly than cytoplasmic r-proteins. Based on actual evolutionary rates for representative cytoplasmic r-proteins, this mitochondrial r-protein evolutionary rate corresponds to an amino acid substitution rate of 40 X 10(-10) per site per year, placing mitochondrial r-proteins in the category of rapidly evolving proteins. The mitochondrial r-proteins are apparently evolving at a rate comparable to that of the mitochondrial rRNA, suggesting that functional constraints act more or less equally on both kinds of molecules in the ribosome. It is significant that mammalian mitochondrial r-proteins are evolving more rapidly than cytoplasmic r proteins in the same cell, since both sets of r-proteins are encoded by nuclear genes. Such a difference in evolutionary rates implies that the functional constraints operating on ribosomes are somewhat relaxed for mitochondrial ribosomes. PMID- 3104610 TI - Evolutionary role of posttranslational modifications of proteins, as illustrated by the glycosylation characteristics of the digestive enzyme pancreatic ribonuclease. AB - The glycosylation characteristics of the digestive enzyme ribonuclease are summarized. The evolutionary role of this posttranslational modification is discussed and evidence is presented that selection has much influence on the presence or absence of carbohydrate in glycoproteins and on the positions of the carbohydrate attachment sites. PMID- 3104612 TI - The eye lens crystallins: ambiguity as evolutionary strategy. AB - Comparative studies of the different families of lens-specific proteins of the vertebrates, the crystallins, and their genes reveal several interesting evolutionary features. The origin of alpha-crystallin can be traced back to the small heat shock proteins, while the superfamily of beta gamma-crystallins shows structural similarities with a bacterial spore coat protein. The crystallins display a great diversity within and between species, as well as during development. Ambiguous transcription, mRNA-processing, and translation contribute to this diversity of the crystallins and their expression. These mechanisms include the occurrence of atypical poly-A addition signals, alternative splicing, and the use of two initiation codons on a single mRNA. PMID- 3104613 TI - Protein export in prokaryotes and eukaryotes: indications of a difference in the mechanism of exportation. AB - Investigation of possible variations between prokaryotic and eukaryotic signal sequences of exported proteins has revealed unexpected differences. Apart from the known similarities (presence of a core hydrophobic sequence preceded by a positively charged amino terminus and followed by a flexible structure), we have found that the core is much more rigid in eukaryotic signals than in their prokaryotic counterparts, and that at both ends the constraints are much more stringent in bacteria than in human cells. The differences have been summarized as a set of 17 criteria describing noteworthy features discriminating between the two classes of signal peptides. The program we used permitted each class of sequences to be learned; Escherichia coli sequences were well learned (i.e., they could be recognized by the programs as having common features), whereas human sequences were found to exhibit a much wider variation. Thus it was possible to propose a consensus in the case of the bacterial peptides, but none (or a much looser one) in the case of the human sequences. Two sequences were exceptional among the E. coli signal peptides, those of lipoprotein and plasmid-borne beta lactamase, suggesting that they have special origins or destinations. Finally, the differences found strongly suggest that the mode of secretion is rather different in the two types of organisms, in spite of the common features of the signal sequences. PMID- 3104614 TI - Genomic blot hybridization as a tool of phylogenetic analysis: evolutionary divergence in the genus Drosophila. AB - Comparative, quantitative Southern analysis of genomic DNA, using single-copy sequence probes, potentially is valuable for phylogenetic analysis. We have examined 27 Drosophila species, belonging to two subgenera, seven species groups, and ten subgroups, using a variety of cloned and characterized probes: twelve cloned sequences from D. melanogaster, two from D. pseudoobscura, and two from D. grimshawi. The data are generally congruent with accepted phylogenetic relationships in Drosophila, and confirm or clarify some previously uncertain relationships. The potential and limitations of the method are discussed. PMID- 3104611 TI - Polite DNA: functional density and functional compatibility in genomes. AB - Certain as yet poorly defined functions of DNA appear to involve collectively domain-sized sequences. It is proposed that most sequence segments within a domain may be either functionally superfluous or instrumental, depending on how many related sequences are present in the domain. When redundant and functionally dispensable, such DNA segments presumably still have to conform to compositional or sequence-motif patterns that characterize the domain. In its relations with neighboring sequences, such DNA is required to be "polite." Polite DNA is DNA that, without being crucially involved in function, is subject to constraints of conformity and, through its base composition, respects a function for which it is not required. This concept is developed by contrasting the distribution of specific and general functions over DNA with this distribution as found in proteins and by distinguishing functional compatibility from pivotal functionality. The sequence constraints to which heterochromatin as well as, apparently, long interspersed repetitive sequences are known to be subject seem to imply that DNA, even when it does not carry out a pivotal function, is indeed, at the very least, required to be polite. PMID- 3104615 TI - The number of nucleotides required to determine the branching order of three species, with special reference to the human-chimpanzee-gorilla divergence. AB - A mathematical theory for computing the probabilities of various nucleotide configurations among related species is developed, and the probability of obtaining the correct tree (topology) from nucleotide sequence data is evaluated using models of evolutionary trees that are close to the tree of mitochondrial DNAs from human, chimpanzee, gorilla, orangutan, and gibbon. Special attention is given to the number of nucleotides required to resolve the branching order among the three most closely related organisms (human, chimpanzee, and gorilla). If the extent of DNA divergence is close to that obtained by Brown et al. for mitochondrial DNA and if sequence data are available only for the three most closely related organisms, the number of nucleotides (m*) required to obtain the correct tree with a probability of 95% is about 4700. If sequence data for two outgroup species (orangutan and gibbon) are available, m* becomes about 2600-2700 when the transformed distance, distance-Wagner, maximum parsimony, or compatibility method is used. In the unweighted pair-group method, m* is not affected by the availability of data from outgroup species. When these five different tree-making methods, as well as Fitch and Margoliash's method, are applied to the mitochondrial DNA data (1834 bp) obtained by Brown et al. and by Hixson and Brown, they all give the same phylogenetic tree, in which human and chimpanzee are most closely related. However, the trees considered here are "gene trees," and to obtain the correct "species tree," sequence data for several independent loci must be used. PMID- 3104617 TI - Silent nucleotide substitutions and G + C content of some mitochondrial and bacterial genes. AB - The G + C content of DNA varies widely in different organisms, especially microorganisms. This variation is accompanied by changes in the nucleotide composition of silent positions in codons. (Silent positions are defined and explained in the text). These changes are mostly neutral or near neutral, and appear to result from mutation pressure in the direction of increasing either A + T (AT pressure) or G + C (GC pressure) content. Variations in G + C content are also accompanied by substitutions at replacement positions in codons. These substitutions produce changes in the amino acid content of homologous proteins. The examples studied were genes for 13 mitochondrial proteins in five species, and A and B genes for bacterial tryptophan synthase in four species. In microorganisms, varying AT and GC mutational pressures, presumably resulting from shifts in the DNA polymerase system, exert strong effects on molecular evolution by changing the G + C content of DNA. These effects may be greater than those of random drift. The effects of GC pressure on silent substitutions in the systems examined are several times as great as the effects on replacement substitutions. GC pressure is exerted on noncoding as well as coding regions in mitochondrial DNA. This is shown by the close correlation (correlation coefficient, 0.99) of the G + C content of the noncoding D loop of mitochondria with the G + C content of silent positions in the corresponding mitochondrial genes. PMID- 3104616 TI - An evolutionary perspective on synonymous codon usage in unicellular organisms. AB - Observed patterns of synonymous codon usage are explained in terms of the joint effects of mutation, selection, and random drift. Examination of the codon usage in 165 Escherichia coli genes reveals a consistent trend of increasing bias with increasing gene expression level. Selection on codon usage appears to be unidirectional, so that the pattern seen in lowly expressed genes is best explained in terms of an absence of strong selection. A measure of directional synonymous-codon usage bias, the Codon Adaptation Index, has been developed. In enterobacteria, rates of synonymous substitution are seen to vary greatly among genes, and genes with a high codon bias evolve more slowly. A theoretical study shows that the patterns of extreme codon bias observed for some E. coli (and yeast) genes can be generated by rather small selective differences. The relative plausibilities of various theoretical models for explaining nonrandom codon usage are discussed. PMID- 3104618 TI - Evolutionary aspects of trypanosomes: analysis of genes. AB - The genes for four glycolytic enzymes of Trypanosoma brucei have been analyzed. The proteins encoded by these genes show 38-57% identity with their counterparts in other organisms, whether pro- or eukaryotic. These data are consistent with a phylogenetic tree in which trypanosomes diverged very early from the main branch of the eukaryotic lineage. No definite conclusion can be drawn yet about the evolutionary origin of glycosomes, the microbodies of trypanosomes which contain most enzymes of the glycolytic pathway. A bias could be observed in the codon usage of the glycolytic genes and genes for other housekeeping proteins, indicating that trypanosomes may have selected a nucleotide sequence that enables efficient translation. However, the genes for variant surface glycoproteins (VSGs) do not show such a bias. This lack of preference for special codons is explained by the high evolutionary rate that could be observed for VSG genes. PMID- 3104619 TI - The 3' ends of two genes in the Balbiani ring c locus of Chironomus thummi. AB - The 3'-end sequences of two nonallelic genes derived from the Balbiani ring c (BRc) locus of Chironomus thummi are described. Only one of the genes appears to be transcribed abundantly in normal late larval salivary glands. The two sequences are highly similar, even in the 3' untranslated regions, but sharply diverge beyond the polyadenylation site. Together with evidence from the 3' ends of BR1 and BR2 genes of C. pallidivittatus and C. tentans, independently characterized by others, this result suggests the existence of a sequence homogenization mechanism that operates across the 3' ends of all BR genes characterized to date. The 3'-terminal coding region of each BRc gene is divided into two portions by a short intron. The upstream portion is homologous to and continuous with the tandem repeats that make up the internal core of each BR gene; however, that portion is variant in sequence relative to the core, and apparently is not subject to the homogenization process that operates on the core repeats. The portion downstream of the intron encodes a unique, 111-residue polypeptide highly different from the rest of the BRc product. The evolution of the various segments of the BRc genes is discussed. PMID- 3104620 TI - Porous carbon implants. Induction of a cement-like layer. PMID- 3104621 TI - Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients. AB - It is current clinical practice to give intravenous nutrition (IVN) to critically ill postoperative septic intensive care patients to prevent loss of body protein, although it has not hitherto been possible to confirm this by direct measurement of body composition. Using a neutron activation analysis facility adapted to provide an intensive care environment and tritiated water dilution we directly measured total body water, protein and fat before and after 10 days of IVN (mean daily non-protein energy and amino acid intakes 2,750 kcal and 127 gm) in eight adult intensive care patients. All patients had recovered from the septic shock syndrome but were still ventilator dependent at the start of IVN. Six patients survived to leave hospital. As a group, the patients lost 12.5% of body protein (mean loss 1.5 +/- SE 0.3 kg; p = 0.001) despite a gain in fat (mean 2.2 +/- 0.8 kg; p = 0.026). There were, in addition, large losses of body water in most patients (mean, 6.8 +/- 2.6 kg; p = 0.036). We conclude that substantial losses of body protein occur in critically ill septic patients despite aggressive nutritional support and that further research is urgently required on the fate of infused substrates and the efficacy of alternative nutritional therapies. PMID- 3104623 TI - The effect of intraportal six-hydroxy-dopamine on hemorrhage after standardized liver trauma in rats. AB - Sympathetic denervation of the liver was accomplished by intraportal injection of 6-hydroxy-dopamine in rats. The animals were subjected to standardized liver trauma 1 week later. Blood loss and duration of bleeding from the cut raw surface were more than doubled in the denervated animals. Mean arterial blood pressure was significantly lower in the denervated animals, but stable during hemorrhage in both denervated and innervated animals. Platelet aggregation and the intrinsic coagulation system were not affected by the chemical denervation. Hepatic norepinephrine was almost eliminated by the denervation procedure. These findings suggest that the liver nerves at the porta hepatis should be preserved during hepatic resections. PMID- 3104622 TI - The blood F VIII:Ag/F VIII:C ratio as an early indicator of deep venous thrombosis during post-traumatic immobilization. AB - Twenty-two consecutive patients with spinal fractures (eight with spinal cord injuries) were studied. All patients were immobilized in bed for 6 weeks after trauma. The occurrence of deep venous thrombosis (DVT) was detected by the 125I labeled fibrinogen test and confirmed by venography. F VIII:C, F VIII:Ag, and AT III activities were determined 2, 6, and 10 to 12 days after trauma. All paralyzed patients (n = 8) developed DVT and two of them had pulmonary embolism within 5 days after trauma. F VIII:Ag and F VIII:C disproportionally increased and the values of F VIII:Ag/F VIII:C ratio above 2 predicted DVT. AT III remained normal during the whole immobilization time and the values of DVT(+) and DVT(-) groups were comparable. PMID- 3104624 TI - Comparative trials of regimes for the treatment of urinary schistosomiasis in The Gambia. AB - Alternative regimes for the treatment of Schistosoma haematobium infection were compared in two trials. Praziquantel at a dose of 40 mg kg-1 appeared to cure 63% of a random sample of heavily infected subjects; significantly more than the 18% cured by three fortnightly doses of metrifonate at 10 mg kg-1. However, praziquantel led to a greater incidence of mild, transient side-effects. A single dose of metrifonate was found to be an inadequate treatment in the same group of subjects as it left 53% with an egg count of at least 100 ova/10 ml. A combination of 10 mg kg-1 of metrifonate and 25 mg kg-1 of niridazole had a similar effect to that of a single dose of metrifonate alone and it had more side effects. Reduced doses of praziquantel had less effect on egg counts than the standard regime, but the difference was not significant in the case of 20 mg kg 1. Although a combination of metrifonate and praziquantel, each at 10 mg kg-1, had a greater effect than either constituent alone, the difference was not significant. Factors affecting the choice of drug for use in mass treatment of urinary schistosomiasis in The Gambia are discussed. The present findings suggest that the standard regime of praziquantel should be used or, if this is not possible, a three-dose metrifonate regime. PMID- 3104625 TI - In vitro studies of glucose metabolism of the rabbit urinary bladder. AB - The urinary bladder, as do all smooth muscle organs, depends on the delivery of oxygen and metabolic substrates for proper functioning. Although glucose metabolism has been studied and evaluated for a variety of smooth muscle systems, little is known about carbohydrate metabolism of the urinary bladder. In the present investigation glucose metabolism and glycogen formation of the urinary bladder of the rabbit was studied in vitro. Isolated urinary bladder strips were prepared from bladder base and body and the following metabolic determinations were made: glucose utilization, glycogen formation, CO2, and lactic acid formation. In addition, the effect of insulin on glucose metabolism was investigated. Glucose utilization was similar in bladder base and body (6.57 +/- 0.67 mumols/gm./2 hours in combined tissues). Eighty-one percent of the glucose utilized was metabolized to lactate whereas 11% was oxidized to CO2 and 4.7% was incorporated into glycogen. Insulin caused a small but significant increase in glucose utilization by bladder strips. PMID- 3104626 TI - The frail, the old, and diagnosis related groups. PMID- 3104628 TI - Cost-effectiveness and the management of pharyngitis. PMID- 3104627 TI - Cost-effectiveness of combined treatment for endocervical gonorrhea. Considering co-infection with Chlamydia trachomatis. AB - Three treatment regimens are currently recommended for penicillin-susceptible Neisseria gonorrhoeae infection of the cervix: ampicillin, tetracycline, and a combination of ampicillin and tetracycline. To evaluate the cost-effectiveness of these options, we developed a decision analysis model and analyzed the efficacy of each treatment in curing gonorrhea, as well as coexisting Chlamydia trachomatis infection, and in preventing subsequent pelvic inflammatory disease, ectopic pregnancy, and infertility. We included direct costs of medication and expenditures for management of unresolved infections and associated complications. Combination treatment is more than twice as cost-effective as tetracycline and seven times as cost-effective as ampicillin when the medical cost of managing pelvic inflammatory disease is considered. When the costs of ectopic pregnancies and infertility are included, the cost-effectiveness of combination treatment increases further. PMID- 3104629 TI - [The effect of CO2 on the coronary circulation--the changes in its responses with a Ca2+ entry blocker]. PMID- 3104630 TI - [Cardiovascular effects of a temporary shunt and nitroglycerin during aortic clamping for resection of a descending thoracic aortic aneurysm]. PMID- 3104631 TI - [The oxygen cost of breathing in critically ill patients]. PMID- 3104632 TI - [Antitumor effects of polyamine antimetabolites with polyamine-free diet]. AB - To evaluate the antitumor efficacy of polyamine antimetabolites such as methylglyoxal-bis-guanylhydrazone (MGBG), ethylglyoxal-bis-guanylhydrazone (EGBG), and alpha-difluoromethylornithine (DFMO), the combined therapies of polyamine antimetabolites with a polyamine-free diet were studied. The combination of EGBG plus DFMO or MGBG plus DFMO showed a marked suppression of tumor growth with a polyamine-free diet; and, when compared, EGBG was slightly superior to MGBG. The inhibition of DNA biosynthesis was also parallel to the above-mentioned results. Furthermore, from an analysis for polyamine levels in tumor tissues, it was confirmed that the polyamine depletion can be maintained by polyamine antimetabolites in combination with a polyamine-free diet in vivo. Moreover, as EGBG has lesser side effects than MGBG, EGBG might be more suitable for clinical use. PMID- 3104633 TI - [Serum apolipoprotein A-I, A-II & B levels in Japanese healthy persons]. PMID- 3104634 TI - [Recent advances in diabetes mellitus]. PMID- 3104635 TI - [A clinicopathological study of 11 patients with acute drug-induced hepatic failure]. PMID- 3104636 TI - [Nursing costs and DRG payments]. PMID- 3104637 TI - [Establishment of the nursing fee in the medical expenses and its history]. PMID- 3104638 TI - Activity of vagal afferent fibers innervating CO2-sensitive receptors in the tortoise, Testudo hermanni. AB - Experiments were done on the tortoise, Testudo hermanni (anesthetized), or on its lung-vagus preparation in which all other internal organs had been removed. By recording the afferent impulse patterns in fine strands of the vagus, three kinds of CO2-sensitive receptors were demonstrated. Heymans-type chemoreceptors: Afferents originating from thoracic arterial chemoreceptors fired randomly at amplitudes below 100 microV. Firing frequency increased when the animal was ventilated with CO2-enriched, nitrogen or hypoxic mixtures, or was given NaCN. Intrapulmonary CO2 receptors (IPC). In an artificially ventilated tortoise and in lung-vagus preparations where the lung CO2-fraction (FCO2) was below 2.5%, single units with a spike amplitude above 200 microV fired regularly. When CO2-enriched air was inspired, impulse frequency decreased markedly, and when the lung was washed with air, it returned to the control frequency following the initial excitation. In lung-vagus preparations the impulse frequency did not change with lung inflation, was null for FCO2 greater than 2.5-3.5%, and was inversely proportional to lower FCO2's. Intrapulmonary CO2-sensitive mechanoreceptors: In anesthetized artificially ventilated tortoises, impulse bursts synchronized with inspiration decreased when the animal inspired 5 or 10% CO2 in air. In lung-vagus preparations, slowly adapting mechanoreceptor responses provoked by lung inflation were reduced when the lung was inflated with CO2-enriched air. PMID- 3104639 TI - Change in O2 uptake during rebreathing in hyperoxia in man. AB - In pertaining to PO2 dependency of the pulmonary CO diffusing capacity during rebreathing, the O2 uptake (VO2) and cardiac output (Q) were measured at three different PO2 levels between 100 and 500 Torr. Since the VO2 measured by an O2 injection method is strongly influenced in hyperoxia by a gas exchange ratio (R), a simulation method using a R-PCO2 relation during rebreathing was developed. Gas volume in the lung-bag-system needed in the computation was measured from the difference in O2 concentration between before and after injecting a known amount of O2 into the rebreathing circuit. The accuracy of the volume was checked by comparing it with the volume measured successively with a body box. The VO2 was determined by comparing the simulated O2 and CO2 concentrations in rebreathing gas with the measured ones. The VO2 significantly increased by rebreathing in hyperoxia. To analyze the VO2 increase, the Q was computed by dividing the VO2 by the arteriovenous O2 content difference, which in turn was obtained by dividing the slope of the CO2 dissociation curve by that of the R-PCO2 line. The Q was almost linearly related to the VO2. Since there was no difference in VO2 in steady state breathing between normoxia and hyperoxia, the increase in VO2 and Q seemed to occur transiently. This finding is very important in evaluating the PO2 dependency of the pulmonary diffusing capacity for CO. PMID- 3104640 TI - [Estimation of anti IgE-induced asthma in guinea pigs by the use of Mead's apparatus, and its application in the examination of disodium cromoglycate]. PMID- 3104641 TI - [T-lymphocytosis and lymphokines in bronchoalveolar lavage fluid of a gold salt induced pneumonitis]. PMID- 3104642 TI - [Relation between CIA and principal variables of breathing pattern]. PMID- 3104643 TI - [Congenital broncho-esophageal fistula with a narrow trachea and double esophageal diverticula]. PMID- 3104644 TI - An epidemiologic study on the association between diet and breast cancer. AB - A case-control study of breast cancer was conducted in Hawaii with Japanese and Caucasian women between ages 45 and 74. Each case was matched to one hospital and one neighborhood control. In all, 183 sets of Japanese and 161 sets of Caucasian subjects were interviewed. No statistically significant differences were found between cases and controls in their mean intake of total fat, saturated fat, oleic acid, linoleic acid, animal protein, and cholesterol. Although there was a suggestion that cases consumed more saturated fat and oleic acid than neighborhood controls, the differences were not impressive. Consistent with other case-control studies, the present investigation did not provide strong support for the hypothesis that a high-fat diet is a risk factor for breast cancer. Further work is suggested to clarify the role of diet in determining breast cancer risk. PMID- 3104645 TI - An exploratory case-control study of brain tumors in adults. AB - An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies. PMID- 3104647 TI - Cancer mortality after multiple fluoroscopic examinations of the chest. AB - Total cancer deaths were not increased among 2,074 women and 1,277 men who were fluoroscopically examined an average of 73 and 91 times, respectively, during lung-collapse therapy for tuberculosis (TB). Patients who did not receive this form of therapy (2,141 women and 1,418 men) and general population rates were used for comparison. All subjects were discharged alive from eight TB sanatoria in Massachusetts between 1930 and 1954; the average follow-up was 23 years. Deaths due to breast cancer were not increased among exposed females [standardized mortality ratio (SMR) = 1.0, n = 24], and SMRs greater than 2.1 could be excluded with 95% confidence. In contrast to other series, our inability to detect a breast cancer excess was likely due to lower breast doses (66 rad) and higher average ages at exposure (28 yr) and thus lower sensitivity. A deficit of lung cancer among exposed males and females was observed (SMR = 0.8, n = 26), even though increased risks have been observed among other populations exposed to similar dose levels. The estimated average lung dose was 91 rad, and SMRs greater than 1.2 for lung cancer could be excluded with 95% confidence. Overall, this study indicates that the radiation hazard of multiple low-dose exposures experienced over many years is not greater than currently accepted estimates for breast and lung cancer. For lung cancer the radiogenic risk may be less than predicted from high-dose, single-exposure studies. PMID- 3104646 TI - Effect of a low-fat diet on hormone levels in women with cystic breast disease. I. Serum steroids and gonadotropins. AB - For examination of the effect of a low-fat diet on serum estrogen, progesterone, and gonadotropin levels, 16 patients with cystic breast disease and cyclic mastalgia were studied before dietary intervention and at 2 and 3 months thereafter. Four-day food diaries indicated that total fat intake was reduced from a prediet average of 69 g (35% of total kilocalories/day) to an average of 32 g (21% of total kilocalories) after 3 months. Highly significant reductions (P less than .001) occurred in dietary cholesterol and less changes occurred in protein and total kilocalorie consumption (P less than .05); fiber intakes were not affected. After 3 months on this low-fat diet, there were significant reductions in luteal-phase serum total estrogens (P less than .001), estrone (P less than .005), and estradiol (P less than .01); progesterone, luteinizing hormone, and follicle-stimulating hormone levels were unchanged. Two of the 16 patients were excluded from the hormone statistical analyses because the serum progesterone levels were not consistent with sampling in the luteal phase of the menstrual cycle. It is concluded that a reduction of dietary fat intake to 20% of the total kilocalories will result in significant decreases in circulating estrogens in benign breast disease patients and that this effect is achievable without increasing dietary fiber consumption. Absence of changes in serum progesterone and gonadotropins during the dietary intervention is consistent with altered enterohepatic circulation of estrogens rather than with effects on the pituitary-ovarian axis. PMID- 3104648 TI - Alcohol consumption and breast cancer. AB - The association between alcohol consumption and breast cancer was investigated in a case-control study involving 1,524 cases and 1,896 controls identified through a nationwide screening program. Ever drinking alcohol was not associated with any substantial increase in risk [odds ratio (OR) = 1.1; 95% confidence interval (Cl) = 1.0-1.3], but there was a significant trend in risk with increasing average weekly intake (P less than .04). Women who had one or fewer drinks daily (83% of all drinkers) did not experience any excess risk compared to nondrinkers, but significant excess risks were observed among those who drank from 1 to 2 (OR = 1.3; 95% Cl = 1.0-1.7) or more than 2 (OR = 1.7; 95% Cl = 1.2-2.4) drinks a day. An increased risk associated with alcohol consumption was evident only for those who drank at younger ages (less than 30 yr), regardless of current consumption. Alcohol effects were adjusted for a variety of factors, including reproductive history, were adjusted for a variety of factors, including reproductive history, socioeconomic indicators, and obesity, but none exerted any appreciable confounding influence. The results support an association between moderate alcohol consumption in early life and subsequent breast cancer risk, although interpretation should be cautious in the absence of dietary information. PMID- 3104649 TI - Prior dietary protein intake and DNA-binding 7,12-dimethylbenz[a]anthracene metabolites formed by isolated rat hepatocytes. AB - Hepatocytes were isolated from noninbred Sprague-Dawley rats previously fed diets containing 7.5 or 15% protein. These hepatocytes were incubated in the presence of exogenous DNA for examination of their ability to metabolize 7,12 dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6] and release reactive DNA-binding metabolites to the medium. An increased formation of extracellular water-soluble metabolites of DMBA was observed in hepatocyte cultures from rats fed a 15% protein diet compared with that in cells from rats fed 7.5% protein. As dietary protein increased, there was a reduction in the release of DNA-binding metabolites by isolated hepatocytes. Bay-region dihydrodiol-epoxide adducts were formed with extracellular calf thymus DNA and hepatic DNA. However, most of the binding of DMBA with extracellular and intracellular DNA was due to unidentified DMBA-DNA adducts that eluted, upon reversed-phase chromatography, after the bay region dihydrodiol-epoxide DMBA adducts were formed. The present studies show that feeding animals diets that are limiting in protein results in a decrease in DMBA detoxification and an increase in excretion of reactive DMBA metabolites from the liver. These results may explain the previously observed influence of dietary protein on the initiation of DMBA-induced mammary carcinogenesis in the rat. PMID- 3104650 TI - Androgen therapy in hemodialysis patients: I. Effects on red cell oxygen transport. AB - Measures related to red cell oxygen transport were evaluated in 17 hemodialysis patients receiving androgen therapy, 15 untreated hemodialysis patients and 15 normal subjects. Hemoglobin levels were higher in androgen-treated patients than in the untreated population and were directly related to the reticulocyte index. Hill coefficients were normal, and in vivo P5O values were increased to the same degree in both dialysis groups. However, DPG and serum phosphate explained 70% and 12%, respectively, of the variance in P5O in untreated patients but only 2% and 5% in androgen-treated subjects. In contrast, sample pH explained 34% of the variance in P5O in the androgen-treated group and less than 1% in the untreated dialysis population. Despite the relative importance of pH as a determinant of P5O in patients on androgen therapy, the Bohr coefficient in this group was only about half of that in untreated dialysis subjects. Androgen-treated patients also had lower red cell ATP levels. Finally, the expected correlation of MCHC with pH was noted in untreated dialysis subjects but not in patients receiving androgens. We conclude that androgen therapy in hemodialysis patients in addition to increasing red cell production, directly alters red cell metabolism. Moreover, although the androgen regimens used did not change the net oxygen transport characteristics of hemoglobin, they decreased the responsiveness of hemoglobin oxygen affinity to changes in pH, DPG and phosphate. Thus, red cell adaptation to changes in oxygen supply and/or demand may be limited in androgen treated patients, and the improvement in clinical performance expected from androgen stimulated erythropoiesis may not be realized. PMID- 3104651 TI - Interaction of Tamm-horsfall protein with bacterial extracts. AB - Crude extracts of uropathic Escherichia coli have been reported to inhibit the binding of human Tamm-Horsfall protein (THP) to homologous and heterologous anti THP antibody in immunoassays. This phenomenon was believed to be due to immunologic cross reactivity between THP and the bacterial antigens for the same antibody. Our attempts to further purify and characterize these "cross reactive" antigens with ion exchange and molecular sieve chromatography were unsuccessful. When purified anti-THP antibody was conjugated to sepharose beads forming an immunoadsorption column capable of isolating THP and cross reactive antigens from solution, the bacterial extracts did not react with the affinity column. However, binding between THP and the bacterial extracts and between THP and whole bacteria were demonstrated. These findings suggest that the cross reactivity seen in the immunoassays is caused by the interaction between the bacterial extracts and THP, and is not representative of true immunologic cross reaction for a common antibody. PMID- 3104652 TI - [Biliary tract procedures using the percutaneous transhepatic approach (review of the literature)]. PMID- 3104653 TI - [Treatment of incompetent biliodigestive anastomoses]. PMID- 3104654 TI - Effect of hypometabolism on cell injury. AB - Rats were given galactosamine 1 g/kg i.p. Pretreatment with propylthiouracil 14 days prior to intoxication and surgical thyroidectomy 10 days prior to intoxication significantly reduced the elevation of SGOT and GLDH activities and protected against hepatocellular necrosis 28 h after intoxication. T3 and T4 levels decreased significantly within the first 2 days in patients with acute myocardial infarction, while rT3 levels were found to be elevated within this period. TRH and TSH decreased during the first 2 days of the observation period and increased in course of time. The protective role of the "hypometabolic" state is discussed. PMID- 3104655 TI - Antacid protection of gastric mucosa. AB - Antacids containing aluminum hydroxide are protective for the stomach in that they prevent grossly visible mucosal necrosis and hemorrhages produced by noxious agents such as aspirin or absolute ethanol. Histologically, this protective effect is confined mainly to the tissue located deep in the gastric mucosa, essentially comprising gastric glands, while the damage to the surface epithelium is not significantly lessened. Accordingly, integrity parameters of the superficial epithelial layer (potential difference, mucus secretion, cell desquamation) do not indicate a protective action of antacids against damage by necrotizing agents. By contrast, significantly diminished microbleeding rates do suggest that protection by antacids works at a level deeper within the mucosa. The protective action of antacids may be mediated, at least in part, by endogenous prostaglandins, which were found to be elevated in this context. PMID- 3104656 TI - Is arachidonic acid protected gastric mucosa more resistant to rechallenge with a second dose of ethanol? AB - In our previous studies we found that pretreatment with arachidonic acid protects the gastric mucosa against ethanol-induced injury. In the present experiments we studied whether: gastric mucosa protected with arachidonic acid against ethanol injury is more resistant to a subsequent second ethanol injury, and whether a second ethanol dose produces further damage of the nonprotected damaged gastric mucosa in a control group. We found that: rechallenge with a second ethanol dose increases the extent of gastric mucosal necrosis in control rats; once protected (with arachidonic acid) the gastric mucosa is more resistant to subsequent ethanol rechallenge but some deep necrosis occurs and restoration of the surface epithelium is somewhat impaired when compared to the initial injury and repair. Thus, pretreatment of the gastric mucosa with a prostaglandin precursor dietary essential fatty acid confers excellent protection against alcohol damage with some residual protective activity against a subsequent rechallenge with alcohol. PMID- 3104657 TI - Prostaglandins and peptic ulcer disease: nocturnal administration of rioprostil vs ranitidine in duodenal ulcer healing. AB - Hypochlorhydria induced by potent antisecretory drugs is followed by a marked elevation of serum gastrin levels which leads to changes in ECL cell density in rats. "Soft" antiulcer drugs like prostaglandins do not increase gastrin levels. Their use in peptic ulcer disease seems to be mainly limited by a relatively high incidence of diarrhea and abdominal cramps. Rioprostil is a new prostaglandin E1 analogue. We compared the potency and duration of action of rioprosil 600 micrograms nocte with 300 micrograms bid on human gastric secretion in a placebo controlled double-blind study. We further evaluated the clinical effectiveness of rioprostil 600 micrograms nocte in the acute treatment of duodenal ulcer. Nocturnal gastric acidity (24:00 to 08:00) was inhibited from 54.5 +/- 1.7 mmol H+/L (placebo experiments; n =9) to 26.7 +/- 3.5 mmol H+/L (52%) by rioprostil 300 micrograms bid (p less than 0.05) and to 14.4 +/- 3.8 mmol H+/L (74%) by rioprostil 600 micrograms nocte (p less than 0.05). During the daytime (09:00 to 18:00), H+ activity was reduced by 33% and 15% respectively (n.s.). Two hundred and three patients with endoscopically proven duodenal ulcers were randomly allocated to treatment with either rioprostil 600 micrograms nocte or ranitidine 300 mg nocte for 4 weeks in a prospective double-blind study. The two groups were similar. After 2 and 4 weeks treatment respectively, about 55% and 85% of patients healed on rioprostil 600 micrograms nocte and 55% and 90% on ranitidine 300 mg nocte. There were no differences between the treatment groups in ulcer pain relief.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104658 TI - [Amphotericin B and flucytosine therapy of Aspergillus pneumonia and acute renal failure]. AB - Kidney failure and pneumonia by Aspergillus flavus and A. fumigatus were found in a 56-year-old woman who had received antibiotic and corticoid treatment to control high fever. Her bloody tracheal secretion was a suspension of granule like spore-free colonies of both Aspergillus species. Hemorrhages in mucous membranes and skin suggested a hematogenous dissemination of the fungi. Aspergillus spores in the soil of ornamental plants were assumed to be responsible for the inhalatory infection. The kidney function normalized rapidly under treatment by amphotericin B plus flucytosine and hemodialysis performed eight times. After 29 days of antimycotic treatment (amphotericin B 463 mg, flucytosine 150 g), besides normalization of the kidney function, healing of the pneumonia and bleeding from skin and mucal membranes took place. One and a half years later kidney function and blood parameters were found to be normal. In cases of Aspergillus pneumonia and kidney failure, a combined treatment by hemodialysis and amphotericin B plus flucytosine is recommended. In addition, there is discussion of the general importance of uremia and its influence on the mycotic infection. PMID- 3104659 TI - [Plasma renin activity and aldosterone behavior in critically ill patients]. AB - To investigate the influence of critical illness on plasma renin activity and aldosterone levels and to examine potential inhibitory effects of dopamine therapy on aldosterone responsiveness, we measured plasma renin activity, and potassium and creatinine in serum, as well as the responses of aldosterone, cortisol and prolactin levels to TRH 200 micrograms i.v. + Synacthen 0.25 mg i.v. in 63 unselected, critically ill patients (32 females, 31 males, aged 18-84 years). Of the patients 19 received dopamine treatment (3-13 micrograms/kg/min i.v.); 21 of the patients died in the further course of their disease. Plasma renin activity was increased in 66.7% of the patients and aldosterone levels were elevated in 90.5% of the patients. There were correlations (P less than 0.05) of lethality with plasma renin activity and cortisol levels and correlations (P less than 0.01) of aldosterone concentrations with plasma renin activity and cortisol levels. Whereas dopamine treatment had no inhibitory effect on aldosterone levels before and after stimulation, prolactin stimulation was decreased in dopamine treated patients. Thus, dopamine does not generally lose its potency of hormone inhibition in critically ill patients, but has no influence on the secondary aldosteronism developing regularly in the early phase of critical illness, which is apparently mainly due to the stimulatory effect of ACTH (or ACTH-related pituitary peptides) and is considered an epiphenomen of the stress mechanisms acting upon the patients in this condition. PMID- 3104660 TI - Selective removal of low density lipoproteins (LDL) by precipitation at low pH: first clinical application of the HELP system. AB - The first clinical application of a new extracorporeal procedure (HELP) for the selective elimination of low-density lipoproteins by heparin precipitation at acid pH is described. Plasma, obtained by filtration of whole blood through a 0.2 mu filter, is continuously mixed with an equal volume of an acetate buffer (pH 4.85) containing heparin. After removal of the precipitated heparin complex by filtration, excess heparin is adsorbed to a specially developed filter and the clear plasma filtrate is subject to bicarbonate dialysis/ultrafiltration to restore physiologic pH and remove excess fluid. The calculated efficiency for the elimination of low-density lipoproteins from plasma by HELP is 100% and is therefore comparable to conventional plasmapheresis. The HELP system shows a high degree of specificity with over 80% of total protein being returned to the patient. Over 130 treatment procedures have now been performed. Patient compliance and acceptance have been excellent and no major complications have been observed. PMID- 3104661 TI - Procollagen-III peptide serum levels in Paget's disease of the bone. AB - A commercially available radioimmunoassay kit was used to determine aminoterminal procollagen-III peptide (pNcoll III) serum levels in patients with Paget's disease of the bone and control subjects. In patients with Paget's disease pNcoll III concentrations were significantly elevated. They decreased to varying degrees under chronic therapy with human and salmon calcitonin, disodium ethane 1-hydroxy 1,1-diphosphonate (EHDP), or a combination therapy of EHDP and human calcitonin. The results were compared with the effect on traditional biochemical markers of disease activity: serum alkaline phosphatase and urinary hydroxyproline excretion, both of which reacted more acutely to the various therapies than pNcoll III, although pretreatment correlations were close. The most probable source of pNcoll III is not the Pagetic bone per se, but the vascular, fibrous connective tissue replacing normal bone marrow. PMID- 3104663 TI - [Decubitus ulcer--evaluation of risk]. PMID- 3104662 TI - [Thermodynamics of the state of a multicomponent CO2-CO-H2O-H2-N2 gas mixture in an electrolyzer with a solid electrolyte]. AB - The thermodynamic state of the gas mixture CO2 = CO = H2O = H2 = N2 in the cathode space of the electrolyzer containing a solid electrolyte is investigated. Calculation of the thermodynamic state makes it possible to determine the theoretical voltage of decomposition and concentration of individual components of this mixture at the outlet of the electrolyzer or each electrolytic cell as applied to various modes of operation. Knowledge of these parameters is important to build a technological scheme of a gas mixture regeneration system. Equations of four independent reactions are used to describe thermodynamic equilibrium reactions are used to describe thermodynamic equilibrium of the gas mixture. Particular cases that occur, when one, two or more conditions of the technological process are not satisfied, are considered. PMID- 3104664 TI - [Efficacy of decubitus prevention]. PMID- 3104666 TI - [Prevention and care of decubitus ulcers in community nursing]. PMID- 3104665 TI - [Changes in nursing practices in the prevention and treatment of decubitus ulcers]. PMID- 3104667 TI - [Aspects of methodologic actions in nursing. Supplemental considerations on care planning for decubitus ulcer as an example]. PMID- 3104668 TI - Local myotoxicity of ketamine hydrochloride in the marmoset. AB - An investigation of raised plasma aspartate aminotransferase (AST) in marmosets after intramuscular ketamine injection suggested a local myotoxicity. This was confirmed by a range of histopathological findings from myofibrillar striation loss to necrosis. In addition to the elevations in AST levels, creatine kinase and the lactate dehydrogenase-5 isoenzyme levels were elevated. It was further demonstrated that, although the physical properties of the injectable solution (pH, osmolality) and to a lesser extent the injection procedure itself caused slight changes in plasma enzyme levels, the ketamine was predominantly responsible for the lesion. No hepatic interactions were seen. This effect should be taken into consideration when this anaesthetic is used in the marmoset if the primary objectives of the experiment entail routine blood analyses. PMID- 3104669 TI - A new model of petit mal epilepsy: spontaneous spike and wave discharges in tremor rats. AB - A mutant rat, which was found in a colony of Kyoto:Wistar rats and genetically defined as a tremor rat (tm/tm), developed tremor of the whole body at 2 weeks of age but the tremor gradually disappeared between 6 and 8 weeks of age. The electroencephalogram (EEG) recorded using chronically implanted electrodes showed a 5-7 Hz (mostly 6 Hz) spike and wave complex synchronously in the cerebral cortex and hippocampus accompanied by absence-like seizure in all six tremor rats examined. The spike and wave complex appeared 0.8-1.9 times per minute and lasted for 1-17 s. However, normal EEG activity was observed in the intervening periods, free of absence-like seizure. Thus the tremor rat is considered to be a possible model for studying the pathogenesis and therapy of petit mal epilepsy in humans. PMID- 3104670 TI - Age-related differences in plasmalogen content of erythrocytes from patients with the cerebro-hepato-renal (Zellweger) syndrome: implications for postnatal detection of the disease. AB - Phosphatidylethanolamine plasmalogen levels were determined in erythrocytes from controls and 13 patients with the cerebro-hepato-renal (Zellweger) syndrome. It was found that in Zellweger patients 20 weeks of age or younger, erythrocyte phosphatidylethanolamine plasmalogen levels were lowered whereas in older patients (except in one) normal levels were found. The results obtained suggest a close relationship between the age of the patients at sampling and the phosphatidylethanolamine plasmalogen levels in their erythrocytes. A possible explanation for these findings and the implications for the postnatal detection of Zellweger syndrome are discussed. PMID- 3104672 TI - Identification of cystic fibrosis homozygotes and heterozygotes by isoelectric focusing of serum proteins. AB - Screening of 44 cystic fibrosis homozygotes, 17 heterozygotes and 36 normal controls, by identification of cystic fibrosis protein (CFP), was performed on sera using an improved isoelectric focusing technique. CFP was observed in 91% of homozygotes, 88% of heterozygotes and 8% of normal controls tested. Partial purification of CFP by chromatofocussing indicates that CFP has a molecular weight of about 52,000 u. It is speculated that CFP is a normal serum protein that exhibits a quantitative difference in concentration between CF homozygotes, heterozygotes and normals. PMID- 3104671 TI - Combined xanthine and sulphite oxidase defect due to a deficiency of molybdenum cofactor. AB - Increased urinary excretion of xanthine, hypoxanthine, sulphite, thiosulphate and decreased serum uric acid were observed in an infant with profound failure to thrive. Other clinical findings included refractory seizures, spastic quadriplegia and profound psychomotor retardation. The patient died at 20 months of age. There were no detectable activities for xanthine oxidase and sulphite oxidase in the postmortem liver. Urothione, which is the metabolic excretory product of the molybdenum cofactor for molybdoenzymes was not present in the urine. A deficiency of the molybdenum cofactor which is common to both xanthine and sulphite oxidase is presumed to be the metabolic defect responsible for the absent activities of both enzymes. PMID- 3104673 TI - A new variant of sphingomyelinase deficiency (Niemann-Pick): visceromegaly, minimal neurological lesions and low in vivo degradation rate of sphingomyelin. AB - Three males (aged 10 years, 3 years 9 months and 2 years 8 months) with profound sphingomyelinase deficiency are presented. The sphingomyelin storage in the liver biopsies attained 30-fold, 65-fold and 16-fold increases against controls, respectively. Levels of bis(monoacylglyceryl) phosphate were also increased. In two cases the bone marrow contained foam cells with liquid crystals of sphingomyelin. Besides the visceral involvement dominated by hepatosplenomegaly, all three cases showed discrete, so far stationary (8 years, 42 months and 28 months) neuropathic features and retinal lesions resembling the classical cherry red spot. Electrophysiological examinations showed a variable reduction of peripheral nerve conduction velocity and prolongation of the latencies of somatosensory, visual and auditory evoked potentials. Ultrastructural examination of skin nerves showed a slight storage, mainly in Schwann cells. In some myelinated fibres there were pseudomyelinic ovoids. The cases therefore displayed features of both A and B types of sphingomyelinase deficiency and should be conventionally classified as intermediate. However, the very low levels of in vivo sphingomyelin hydrolysis (not exceeding 6%, against 30 +/- 10% in type B and 77 +/- 5% in controls) were clearly within the range of type A values (5 +/- 2%). Accordingly, we suggest that the cases may be biochemically classified as variants of type A disease. PMID- 3104674 TI - Immunological evidence for a carbamylphosphate synthetase lesion resulting in the formation of enzyme with altered sub-unit size. AB - A partial carbamylphosphate synthetase (CPS: EC 6.3.4.16) deficiency (McKusick 23730) was found in a male child who presented with generalized convulsions, rickets and apnoeic attacks at six months of age. By his second year he showed serious developmental delay and a gut biopsy revealed an absence of CPS activity with an elevated ornithine transcarbamylase activity. Analysis of the gut biopsy sample on SDS-polyacrylamide gels, followed by electrophoretic transfer to a nitrocellulose filter probed with monospecific antibodies to CPS showed that the child had normal levels of immunoreactive enzyme, but instead of one band corresponding to normal CPS with a subunit size of 165,000 u, the patient had three immunoreactive bands, one larger and two smaller than that found in normal controls. The genetic defect in this child therefore results in an unusual form of CPS being made which has markedly reduced enzyme activity. PMID- 3104677 TI - Elimination of mycoplasmas from infected cell cultures by combined trypsin/antibiotics treatment. PMID- 3104676 TI - A new case of arginase deficiency in a Spanish male. AB - A new case of arginase deficiency is reported in a male newborn from Spain. In contrast with the majority of the earlier cases, this infant showed severe protein intolerance of early onset. The diagnosis was based on the assay of the urea cycle enzymes in a postmortem liver sample. Levels of erythrocyte arginase were also determined in the parents and in a sister of the patient, and were consistent with heterozygosity. From a study of the pedigree it appears that arginase deficiency in this family presents a dramatic course. PMID- 3104675 TI - Phosphoglycerate kinase: studies on normal and a mutant human enzyme. AB - Phosphoglycerate kinase was purified from a number of tissues obtained at autopsy from a subject with the deficiency. Properties of the mutant enzyme were compared to those of PGK purified from tissue obtained from normal subjects. The purified enzyme from the propositus contained two components, a minor fraction (about 2 5%) which behaved similarly to the normal enzyme during the purification procedure, and a major fraction (greater than 95%) which could not be purified by the same procedure. The major fraction demonstrated a number of other properties which differed from the normal. These included a tendency to form aggregates, increased heat sensitivity and altered nucleotide substrate specificity. The smaller fraction appeared to have effectively identical properties to that of the normal enzyme. In keeping with its X-linked mode of inheritance, phosphoglycerate kinase from all normal tissues appeared to have identical kinetic properties, although evidence for minor variations, presumably due to post-translational modifications, was obtained. PMID- 3104678 TI - A decrease in glycine cleavage activity in the liver of a patient with dihydrolipoyl dehydrogenase deficiency. PMID- 3104679 TI - Genetic analysis of partial dihydropteridine reductase deficiency in families with mental retardation. PMID- 3104680 TI - Atypical non-ketotic hyperglycinaemia. PMID- 3104681 TI - Phenylketonuria and scleroderma. PMID- 3104682 TI - Pregnancy in and incidence of xanthine oxidase deficiency. PMID- 3104683 TI - A new case of methylmalonic aciduria with unexplained negative urinary methylmalonic colorimetric test. PMID- 3104684 TI - Single cell studies on the immunological marker profile of plasmacytoid T-zone cells. AB - Plasmacytoid T cells (PTC) are known to home to thymic (T) zones in human lymph nodes and are characterized by their abundant, concentrically layered, rough endoplasmic reticulum. These cells have been found in reactive and neoplastic conditions. Three cases of PTC lymphomas have so far been reported. All of them were complicated by a myelomonocytic leukemia leading to the assumption of a functional relationship between PTC and the myeloid system. The immunologic phenotype of PTC, as revealed on frozen tumor tissue sections, comprised the expression of CD5 (T1), CD4 (T4), and HLA-DR, but not CD8 (T8) and CD2 (T11) and suggested an affiliation to the T cell system. Extending our previous report on one of these cases we here present the first study on the immunological marker profile of suspended PTC. The employment of unfractionated or PTC-enriched tumor cell suspensions rendered possible the application of a panel of monoclonal antibodies (moAbs) on both fixed and unfixed cells and enabled us to allocate various markers either to the intracytoplasmic or surface domain of this cell type. Our results suggest that PTC from our case rest in the G0/G1 phase of the cell cycle. They express the transferrin receptor, but not the Il-2 receptor (CD25) or the nuclear antigen Ki-67. No T cell antigen was demonstrated on the surface of unfixed suspended PTC. Under these conditions only HLA-DR and a predominantly monocytic antigen (CD36/moAb 5F1) were identified. Fixed cells, however, showed a weak cytoplasmic reactivity for CD5 and two myelomonocytic antigens (CD15/moAb 1G10 and CD14/moAb My4). Our findings do not sustain positive evidence for a T cell nature of PTC. Whether their phenotypical pattern indicates terminal differentiation with concomitant loss of T cell antigens or points to a cytogenetic relationship of PTC to the myeloid system, remains speculative. Until the cytogenesis of PTC is clarified we propose the noncommitted term "plasmacytoid T-zone cells" for this elusive cell type. PMID- 3104686 TI - The lupus anticoagulant. PMID- 3104685 TI - Analysis of absorptive cell occluding junction structure-function relationships in a state of enhanced junctional permeability. AB - Junctional strand count, the number of individual junctional strands which intersect a perpendicular, has been widely used as a morphological estimate of the ability of an occluding junction to resist passive transjunctional molecular flow. Such junctional analysis, which requires the study of freeze fracture replicas, has been useful in studies of occluding junction structure function relationships in unperturbed epithelia and in intestinal epithelia under conditions which lead to increases in junctional resistance. It is unclear if the above junctional structure-function correlates also exist in intestinal or in other epithelia under conditions which result in a state of enhanced junctional permeability. To gain further insight into occluding junction structure-function relationships under such conditions, we utilized an in vivo hypertonic perfusion model previously shown to result in the transfer of luminal macromolecules into the paracellular space of small intestinal villus epithelium. After a 1-hour perfusion with either 600 mOsmoles or 750 mOsmoles mannitol solutions, the macromolecule horseradish peroxidase diffusely filled the paracellular spaces of the upper half of villi. However, analysis of thin sections showed that only junctions at the tip of villi were leaking this tracer. Freeze fracture analysis revealed occluding junction structural abnormalities most marked at the villus tip thus corresponding to the site of transjunctional horseradish peroxidase leak. The most frequent abnormality noted was loss of strand-strand crosslinking and dilation of the interstrand compartments. At such sites, wide unobstructed channels could be traced through much of the junction. However, the apical junctional strand was never noted to display unequivocal discontinuities. Subsequent in vitro studies of perfused tissues revealed that dose dependent decreases in transepithelial resistance and junctional charge selectivity were induced by hypertonic mannitol perfusions. These studies indicate that: paracellular localization of a luminally applied tracer may result from a transjunctional leak at a distant site with subsequent lateral diffusion of the marker; traditional junctional strand count-function relationships may not hold in states which lead to the rearrangement of junctional architecture; and, at least the apical junctional strand may become permeable to macromolecules without the introduction of morphologically detectable strand discontinuities as assessed by routine freeze fracture techniques.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3104687 TI - Contraceptive steroid treatment affects steroid binding proteins and the percentage of free 17 beta-estradiol and testosterone in the cynomolgus monkey (Macaca fascicularis). AB - The levels of steroid binding globulins were characterized in cynomolgus monkeys that were treated with contraceptive steroid preparations delivered either by intravaginal rings (CVR) or orally (OC) in the diet. Levonorgestrel (dNG) was the bioactive progestin and the estrogen was either 17 beta-estradiol (E2) in the CVR treatment or ethinyl estradiol (EE) in the OC treatment. Both contraceptive treatments lowered sex hormone binding globulin (SHBG) levels below those observed in males (P less than 0.05) and normal females (P less than 0.01). Corticosteroid binding globulin (CBG) was elevated (P less than 0.01) in the OC treatment, demonstrating the potency of EE. The distribution of E2 and testosterone (T) between binding to SHBG or albumin and the unbound fraction was calculated after the determination of the percentage of free steroid by centrifugal ultrafiltration. Both contraceptive treatments increased the percentage of free T and E2 (P less than 0.01) in the subset of monkeys that were evaluated, but the percentage bound to SHBG and albumin were different only for the CVR group (P less than 0.05). Decreased total T concentrations in the treatment groups offset any increase in free T concentrations associated with an increase in the percentage of free T. The differences in the distribution of binding to SHBG associated with these contraceptive steroid treatments was influenced more by the reduction in the binding capacity of SHBG than by the displacement of E2 and T from SHBG by dNG. PMID- 3104688 TI - [Aldose reductase inhibitors]. AB - Aldose reductase (AR) is an enzyme which catalyzes the transformation of D glucose to sorbitol. Under non physiological conditions, like diabetes for example, the accumulation of polyols in the lens, sorbitol in particular, gives a basis to the osmotic hypothesis of cataract formation. AR inhibitors can protect against such accumulation. Oxidation of the constituents of the lens is a primary phenomenon in cataract formation, and some authors have suggested that the autoxidation of monosaccharides would originate the formation of cataract. For these authors, AR inhibitors would act by trapping the radical intermediates formed, inhibiting the denaturation of proteins in the organ and the lowering of glutathione. There classes of AR inhibitors can be distinguished: flavonoids and their related compounds, spirohydantoins--like sorbinil--and related compounds, and compounds with an acid function such as alrestatine. For each of these three classes, the authors try to establish the structure-activity relationship of the molecules. The possibility of a single site of interaction between AR and the different AR inhibitors is discussed. Differences in the inhibitory effect for a given compound between species, and for one species between tissues have been underlined. PMID- 3104689 TI - Role of intracellular calcium stores in the contractile response of uterus to several agonists. AB - A comparison was made of contractions produced by submaximal doses of oxytocin, noradrenaline, PGE2 and PGF2 alpha in estrogen-dominated rat uterus after the preparation had been loaded in Ca-free medium supplemented with EDTA 3 mM. The experiments were carried out in the presence of EDTA 1 mM to complex the contaminating Ca. The contraction was sustained as long as the preparation was exposed to the drug and was relaxed by washing. Cumulative concentration-response curves to oxytocin (6.25-100 microM), noradrenaline (0.05-1.6 mM), PGE2 (0.1-1.6 microM) and PGF2 alpha (0.02-0.32 microM) were made. The threshold concentration for PGF2 alpha was much lower than for PGE2, oxytocin and noradrenaline. Isoprenaline (10- -10(-4)M), KCl (56.3 mM) and caffeine (5 mM) were added. The results showed that isoprenaline and KCl did not produce contractile response. Caffeine produces only a small decrease in the resting tension and this effect is not reversible. After addition of noradrenaline, a concentration of oxytocin (6 microM) produced a uterine contraction smaller than the control response of uterus to oxytocin. The response to the oxytocin applied after washing out the caffeine was the same as the control response. All agonists tested that were capable of inducing uterine contraction in Ca-free medium act through specific receptors. This suggests a relation between receptor-operated Ca-channels and intracellular Ca-stores. PMID- 3104690 TI - Preliminary phytochemical, pharmacological and antibacterial studies of the alkaloidal extracts of the leaves of Synclisia scabrida Miers. AB - Preliminary phytochemical investigation of the leaves of Synclisia scabrida indicated the presence of two alkaloids in the water extracts and five alkaloids in the ethanol extracts. The alkaloidal fraction obtained from the cold ethanol extract furnished on column-chromatography, a homogeneous amorphous solid which has been designated as alkaloid C. Alkaloid C showed positive test for alkaloids. The UV and IR spectra and colour reactions of alkaloid C indicated that the compound may be a phenolic bisbenzylisoquinoline alkaloid. All the extracts delayed the onset and shortened the duration of apomorphine-induced stereotyped behaviour in chicks. In addition, 40 mg kg-1 i.p. of the ethanolic extract induced catalepsy in rats. The cold water extract (CWE) synchronized the EEG of the hyperstriatum, optic tectum and the reticular formation while the EMG activity was slightly enhanced. The hot ethanol alkaloidal extract (HEE) inhibited the growth of Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration of HEE on Pseudomonas aeruginosa strains I and II were 5 and 2.5 micrograms/ml while for Staphylococcus aureus strains I and II were 5 and 10 micrograms/ml, respectively. Up to 1 g kg-1 i.p. of the extract failed to induce any lethal effect in chicks and rats. These effects of the leaf extracts of Synclisia scabrida Miers support some of the local uses of the plant by traditional medical practitioners. PMID- 3104691 TI - In vivo activity of an extract of Pavetta owariensis bark on experimental Schistosoma mansoni infection in mice. AB - Mice were experimentally infected with Schistosoma mansoni. Comparisons were carried out of total body weight, weight of liver, spleen and left lung, number of adult worms and eggs, and size of liver granulomas between an untreated group and a group treated only with an alcoholic extract of Pavetta owariensis. In the treated group, liver granulomas were smaller for both the acute and chronic infections, indicating a modulation of the granulomatous reaction. A reduction of worm burden, especially of male worms was observed after treatment of chronically infected mice with the same extract. PMID- 3104692 TI - Comparison of continuous-wave lasers for endarterectomy of experimental atheromas. AB - The standard surgical lasers, argon ion, neodymium-yttrium aluminum garnet, and carbon dioxide, are often operated as continuous wave lasers with specific uses. Clinical trials of laser therapy for arteriosclerotic cardiovascular disease are underway with all three lasers. Therefore, we compared these three lasers under controlled experimental conditions. A thoracoabdominal exploration was performed in 17 arteriosclerotic rabbits. The aorta was isolated, heparin administered, and multiple endarterectomies were performed in each rabbit with each of the lasers. A line of laser craters was created at the proximal and distal ends of an atheroma. Continuous-wave laser radiation was used to connect the craters and thereby form proximal and distal end points. The plaques were dissected free from the aorta with laser light and the end points were fused by laser. The aortas were removed for light microscopy and the animals were killed. The endarterectomy surfaces and end points were serially sectioned and graded according to light microscopic findings (1 = worst, 4 = best). Argon ion laser endarterectomy (N = 16) required 106 +/- 10 J/cm2. The surface score was 3.5 and end point score 3.4. Neodymium-yttrium aluminum garnet laser endarterectomy (N = 13) required 1,289 +/ 115 J/cm2 with a surface score of 2.4 (p less than 0.001 from argon ion) and an end point score of 1.3 (p less than 0.001 from argon ion). Carbon dioxide laser endarterectomy (N = 9) required 30 +/- 5J/cm2 with a surface score of 2.0 (p less than 0.001 from argon ion) and and end point score of 1.6 (p less than 0.001 from argon ion). Perforation occurred in one of 16 argon ion studies (technical error, not laser), in 11 of 13 neodymium-yttrium aluminum garnet studies, and in six of nine carbon dioxide studies. This study demonstrates that of the currently available clinical continuous-wave lasers, the argon ion laser is superior for endarterectomy of experimental atheromas. PMID- 3104693 TI - Blood conservation for myocardial revascularization. Is it cost effective? AB - A total of 284 patients undergoing myocardial revascularization were prospectively studied to determine if the use of intraoperative autotransfusion or intraoperative autotransfusion plus postoperative reinfusion of shed mediastinal blood decreased transfusion requirements and the use of one or both techniques was cost effective. The Haemonetics Cell Saver System was used for intraoperative autotransfusion and the Sorenson Receptaseal autotransfusion system for postoperative reinfusion of shed mediastinal blood. During Phase 1, the Cell Saver System was used for 57 patients and 93 patients served as a control group. During Phase 2, the Cell Saver System plus the autotransfusion system were used in 43 patients and 91 patients were in the control group. Separate parallel analyses to compare the blood conservation groups to control groups were conducted for each phase of the study. The patient groups were comparable with regard to age, sex, preoperative red cell mass, preoperative hematocrit value, number of bypasses, and use of internal mammary grafts. Blood conservation techniques resulted in significant reductions in the use of bank blood. During Phase 1, Cell Saver System patients received an average of 2.8 units of packed cells versus 4.7 units for control patients. Transfusion was avoided entirely in 14% of Cell Saver System patients compared to 3% of control patients. During Phase 2, patients subjected to both the Cell Saver System and the autotransfusion system received an average of 1 unit of packed red cells versus 3 units for control patients. Transfusion was required in only 42% of patients subjected to both the Cell Saver System and the autotransfusion system compared to 85% of control patients. Multiple logistic regression analysis confirmed that the use of the Cell Saver System in Phase 1 and the Cell Saver System and autotransfusion system in Phase 2 were each independently predictive of decreased transfusion requirements. The total "blood-related costs" (including cost for all bank blood products plus Receptaseal and Cell Saver System equipment) was slightly lower for the blood conservation patients in both Phase 1 ($555.00 versus $615.00, no significant difference) and Phase 2 ($373.00 versus $426.00, no significant difference). Intraoperative use of the Cell Saver System is associated with substantial savings of bank blood, and the addition of postoperative reinfusion of shed mediastinal blood results in further bank blood savings. The use of blood conservation techniques is cost effective; that is, the costs incurred for the blood conservation equipment are more than offset by the resultant dollar savings for blood products. PMID- 3104694 TI - Repeat sternotomy after reconstruction of the pericardial sac with glutaraldehyde preserved equine pericardium. AB - The risk of repeat sternotomy is higher than that of the initial sternotomy, especially if the pericardial sac was left open at the first intervention. In 200 consecutive patients with a pericardial defect after open heart operations, the pericardium was closed with a glutaraldehyde-preserved equine pericardial patch. Precardiac adhesions at reoperation were assessed in four groups of patients on a scale of 6, ranging from 0 (no adhesions) to 5 (calcified or ossified adhesions). Group I comprised 13 patients in whom the pericardium was left open at the first operation and an equine pericardial patch was implanted at reoperation. Group Ia included the first five Group I patients who underwent reoperation less than 1 year (early reoperation) after the initial procedure. Group Ib included the other eight patients of Group I, who underwent reoperation more than 1 year (late reoperation) after the first procedure. Group II comprised nine patients who were reoperated on after reconstruction of the pericardial sac with a glutaraldehyde preserved equine pericardial patch. After a mean follow-up of 20.2 months, the incidence of patch-related complications was 1%. Statistical analysis shows less severe adhesions on reoperation in Group II patients (pericardial defect patched) than in Group I patients (pericardial defect left open): mean grade of adhesions 1.6 +/- 0.9 (Group II) versus 3.2 +/- 0.6 (Group I), p less than 0.001. Precardial adhesions with the pericardium left open were similar in patients having early and late reoperations: mean grade of adhesions 3.0 +/- 0.7 (Group Ia) versus 3.4 +/- 0.5 (Group Ib), no significant difference. Therefore, the glutaraldehyde-preserved equine pericardial patch can be considered a suitable material for primary closure of the pericardial sac in patients with inadequate autologous pericardium. PMID- 3104695 TI - Lymphoblastic lymphoma expressing natural killer cell-associated antigens: a clinicopathologic study of six cases. AB - We describe six patients with lymphoblastic lymphoma (LBL) whose neoplastic lymphoid cells expressed surface antigens associated with natural killer (NK) cells. The six cases were selected from a series of 38 specimens diagnosed as LBL based on morphologic criteria and further subclassified by the use of an extensive panel of monoclonal and polyclonal antibodies. Although the morphologic features in all six cases were similar to those previously reported for LBL, their expression of NK-associated antigens was unique. All cases were positive with anti-Leu 11b, an antibody which appears to define a specific subtype of lymphocytes considered to have NK function; and all cases expressed T11, a T-cell restricted antigen. The most commonly encountered immunophenotype of our cases of LBL was: Leu 11b+, T11+, Leu7+, TdT+, Leu 3a+, Ia+, pre-B-, and B-. As compared with more classical LBL of T-cell type, LBL of NK-cell type in our series occurred primarily in females and non-whites. Whereas treatment of classical LBL by multi-agent chemotherapy may lead to long-term survival, only two of our six patients were long-term survivors. The data derived from this study raise the possibility that LBL with the antigenic phenotype of NK cells may represent a biologic subtype of LBL. PMID- 3104696 TI - Pulmonary clearance of 99mTc-DTPA: a noninvasive assessment of epithelial integrity. PMID- 3104697 TI - Lung surfactant: how it does and does not work. PMID- 3104698 TI - Autoanticoagulation does not preclude pulmonary emboli. PMID- 3104700 TI - Bronchodilating effects of the anesthetic ketamine in an in vitro guinea pig preparation. PMID- 3104699 TI - Mechanisms affecting exercise performance in subjects with asbestos-related pleural fibrosis. PMID- 3104701 TI - Effects of adrenalectomy and thyroidectomy on postnatal rat lung development and cytoplasmic factors modulating adenylate cyclase activity. PMID- 3104703 TI - Effect of cigarette smoking on structure of the small airways. PMID- 3104704 TI - [Loss of resistance to chloramphenicol of clinical strains of Pseudomonas aeruginosa after infection with phage 119 X]. PMID- 3104705 TI - [Schistosomiasis as a possible cause of appendicitis in a person who visited an endemic region]. PMID- 3104706 TI - [Treatment of nasopharyngeal cancer with recombinant gamma interferon (IFN). A report based on 2 patients]. AB - Patients with advanced NPC and tumour relapses were efficiently treated with recombined gamma-interferon in some instances. The authors report on two selected cases with elevated EBV titres who belonged to the "high-risk group" and had an unfavourable prognosis. Both patients were treated with gamma-interferon over a period of 6 months and the EBV titres decreased. No relapses have been observed until now. Radiation therapy (RT) is the treatment of choice in NPC. Chemotherapy does not show any advantage in respect of relapse-free survival and overall survival. Interferon seems to be an efficient therapy in selected cases. Questions regarding the effectiveness, the dosage and side effects of the individual classes of interferons are still unclear and should be an important task for further research. PMID- 3104702 TI - alpha-1-Antitrypsin and the pathogenesis of emphysema. PMID- 3104707 TI - [Drug therapy of peptic ulcer. What is coming up?]. AB - Prostaglandin-E analogues inhibit gastric acid secretion after oral administration. Therefore, these drugs are tested in clinical trials and one of them--Misoprostol--has recently been registered. With regard to healing rate of peptic ulcers and improvement of clinical signs and symptoms the prostaglandin analogues are superior to placebo but only equally effective or even slightly inferior to H2-receptor blockers. Side effects such as diarrhea or uterotropic actions will probably limit their broad application. The exact therapeutic effectiveness of prostaglandin analogues in treatment of peptic ulcer remains to be evaluated in greater detail. The substituted benzimidazole omeprazole is the first drug which exerts a long lasting and almost complete suppressive effect on gastric acid secretion in humans. This unique inhibition leads to a significant and more rapid healing rate of duodenal ulcers compared to treatment with H2 blockers. Additionally, peptic ulcers resistant to H2-blocker therapy can be treated effectively with omeprazole. In spite of these promising results the exact therapeutic effectiveness of this drug requires further evaluation. PMID- 3104708 TI - Opioid modulation of thyrotropin releasing hormone induced prolactin secretion. AB - It is known that opioids stimulate prolactin (PRL) secretion by an action on hypothalamic neurons, but in vitro studies have suggested a direct action on the lactotrophs. The present study was performed on male rats known to have little or no PRL response to TRH. A beta-endorphin (beta EP) injection in the third ventricle stimulated PRL secretion and induced furthermore a PRL secretory reaction to TRH injected intravenously 20 min later. Pretreatment with naloxone 10 min before beta EP injection abolished not only the PRL response to beta EP but also the conjugated effect of beta EP and TRH. Pretreatment with naloxone methyl bromide (Br-naloxone), a quaternary naloxone derivative, which does not cross the blood-brain barrier, had no effect on the PRL response to beta EP but prevented the conjugated effect of beta EP and TRH on PRL secretion. Pretreatment of the animals with -methyl-parathyrosine resulting in a dopamine depletion or with haloperidol, a dopamine antagonist, could not induce lactotroph responsiveness to TRH. These results suggest that beta EP in male rat sensitizes the PRL cell to TRH by a direct effect and not through an inhibition of the dopaminergic tone. PMID- 3104709 TI - Effects of ubiquinones on spontaneous membrane hyperpolarizations in a cloned monkey kidney cell line. AB - The effects of ubiquinones on spontaneous membrane hyperpolarizations in JTC-12 cells were examined. There were three types of spontaneous hyperpolarizations; rhythmic, sporadic and oscillatory types. The oscillatory type was not observed in the standard medium, whereas it was observed in sodium-free medium or in the medium containing 300 nM coenzyme Q10. The number of the cells showing spontaneous hyperpolarizations significantly increased in the medium containing coenzyme Q10 (47.7%) as compared to the control (18.9%). However, coenzyme Q1 (500 nM) showed no effects. PMID- 3104710 TI - The involvement of central cholinergic mechanisms in cardiovascular responses to intracerebroventricular and intravenous administration of thyrotropin-releasing hormone. AB - Intracerebroventricular (i.c.v.) administration of thyrotropin-releasing hormone (TRH) in a range from 0.1 to 100 micrograms induced a dose-related increase in blood pressure in conscious rats, whereas TRH-free acid (TRH-OH) and histidyl proline diketopiperazine (His-Pro-DKP), metabolites of TRH, did not. The blood pressure responses to intravenous (i.v.) injection of 5 mg/Kg TRH were similar to those induced by TRH (i.c.v.). Pretreatment with atropine (50 micrograms, i.c.v.) significantly reduced the pressor effect of TRH administered through either route. Hemicholinium-3 (50 micrograms, i.c.v.), an inhibitor of choline uptake, also prevented the increase in blood pressure induced by TRH (10 micrograms, i.c.v.). These results indicate that both centrally and peripherally administered TRH have pressor effects that are mediated by central cholinergic mechanisms, probably by activating cholinergic neurons. PMID- 3104711 TI - Administration of an LHRH-antagonist to male mice: effects on in vivo secretion of hormones and on the growth of a transplantable human prostatic carcinoma. AB - The potent luteinizing hormone releasing hormone (LHRH) antagonist [N-Ac-D-p-Cl Phe1,2,D-Trp3,D-Arg6,D-Ala10]-LHRH was chronically administered to male nude mice bearing the transplantable human hormone-dependent prostatic adenocarcinoma PC 82. Treatment of tumor-bearing male mice with a daily dose of 100 micrograms (4 mg/kg b w.) for 21 days did not significantly affect the growth of the PC-82 tumor tissue, or the weights of ventral prostate, seminal vesicles and testes. At 24 hours after the last dose of the antagonist the mean plasma-testosterone (T) value in these animals was not different from the control level. Administration of similar doses of the antagonist to intact normal immunocompetent male mice significantly reduced plasma LH concentrations and suppressed plasma-T to near castrate levels, when blood was taken 2 hours after the last injection. At 24 hours after the last dose, however, plasma concentrations of LH and T had returned to control levels. This time-dependent pattern of T suppression by the antagonist was confirmed by a time-course experiment in animals receiving a single dose of the compound. These data demonstrate that a daily high dose of this antagonist cannot effectively suppress plasma-T in male mice. Therefore, the mouse may not be a suitable model for the investigation of the "castration-like" effect of LHRH-antagonists on androgen-dependent prostate xenografts. PMID- 3104712 TI - Spontaneous neural activity of a mechanoreceptive system is undiminished by replacement of external calcium with equimolar magnesium in the presence of EGTA. AB - Primary afferent neurons of the lateral-line mechanosensory organs, which are believed to be closely related to the auditory and vestibular organs, exhibit "spontaneous" action potentials in the absence of mechanical stimulation of the receptor cells (hair cells). Sinusoidal mechanical stimulation of the hair cells enhances the impulse rate of the afferent neurons. The spontaneous activity is found to be a decreasing function of increasing concentration of either external magnesium or calcium, when each cation is varied in the absence of the other and bath-applied to the synaptic side of the lateral-line mechanoreceptors. One mM to 6 mM magnesium with 5 mM EGTA (the latter for chelation of remaining traces of calcium) permits undiminished spontaneous afferent activity of lateral-line neurons for as long as 3 to 4 hours. With bath-applied calcium, mechanical stimulation results in evoked incremental activity--defined as total activity with stimulation minus spontaneous activity--which significantly increases with increasing calcium concentration. However, with magnesium and EGTA in the bath, mechanical stimulation produces no increase in the neural firing rate above spontaneous rate for any magnesium concentration tested. Taken together, these results suggest that spontaneous activity, in contrast to evoked incremental activity, does not require external calcium in the bath, and production of spontaneous neural action potentials may proceed via mechanisms that are modifications of those of classical stimulus-secretion coupling. PMID- 3104713 TI - Effect of phorbol and glucose on insulin secretion from the human fetal pancreas. AB - It has been reported previously that 12-0-tetradecanoylphorbol-13-acetate is capable of stimulating the release of insulin from adult and neonatal pancreatic tissue. The data from this study show that this agent at a concentration of 1.3 uM, in the presence of 2.8 mM glucose, was unable to cause significant secretion of insulin from cultured human fetal pancreatic explants. By contrast 20 mM glucose was able to cause a small but significant immediate increase in secretion of insulin, but was unable to maintain this response beyond ten minutes. When the two agents were combined, a synergistic effect was seen throughout the entire 50 minute period of stimulation. The reason for this synergism is unclear since, whilst both secretagogues were able to cause a rise in the levels of diacylglycerol, together no extra effect was observed. PMID- 3104716 TI - Gonococcal infections: a continuing diagnostic and therapeutic challenge. PMID- 3104715 TI - Metabolism of sterols of varying ring unsaturation and methylation by Caenorhabditis elegans. AB - The metabolism of three dietary 4,4-desmethylsterols and two 4 alpha methylsterols was investigated in the free-living nematode Caenorhabditis elegans. Dietary cholestanol was converted mostly to lathosterol. Dietary lathosterol, 7-dehydrocholesterol, 4 alpha-methylcholest-7-enol and 4 alpha methylcholest-8(14)-enol each remained largely unchanged. An absolute requirement for a substantial quantity of 7-dehydrocholesterol in C. elegans did not exist. C. elegans was unable to remove a 4 alpha-methyl group or introduce a double bond at C-5 and also demonstrated the lack of a delta 7-reductase. Its nutritional sterol requirement was satisfied by cholestanol, lathosterol or 7 dehydrocholesterol; growth was comparable to that obtained previously in media containing delta 5-sterols. However, the two 4 alpha-methylsterols appeared to be unsatisfactory sterol nutrients. The possible physiological importance of 4 alpha methylsterols is discussed briefly. PMID- 3104714 TI - Resolution of radiolabeled molecular species of phospholipid in human platelets: effect of thrombin. AB - Resolution of individual molecular species of human platelet 1,2-diradyl-sn glycero-3-phosphocholines and 1,2-diradyl-sn-glycero-3-phosphoethanolamines by reverse phase high pressure liquid chromatography (HPLC) allowed a thorough analysis of those phospholipids labeled with [3H]arachidonic acid. Approximately 54% and 16% of the total incorporated radiolabel was found in choline glycerophospholipids and ethanolamine glycerophospholipids, respectively, with ca. 90% of this being found in the 1,2-diacyl molecular species. Eighty percent of [3H]-arachidonic acid incorporated into 1-acyl-2-arachidonoyl-sn-glycero-3 phosphocholine in resting platelets was equally distributed between 1-palmitoyl-2 arachidonoyl and 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, while 70% of the radiolabel in 1-acyl-2-arachidonoyl-sn-glycero-3-phosphoethanolamine was found in 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphoethanolamine. Thrombin stimulation (5 U/ml for 5 min) resulted in deacylation of all 1-acyl-2 [3H]arachidonoyl molecular species of 1-acyl-2-arachidonoyl-sn-glycero-3 phosphocholine and 1-acyl-2-arachidonoyl-sn-glycero-3-ethanolamine. There was also a slight increase in 1-O-alkyl-2-[3H]arachidonoyl-sn-glycero-3 phosphocholine and a significant increase in 1-O-alk-1'-enyl-2-[3H]arachidonoyl sn-glycero-3-phosphoethanolamine molecular species of over 300%. Thus, HPLC methodology indicates that arachidonoyl-containing molecular species of phosphatidylcholine and phosphatidylethanolamine are the major source of arachidonic acid in thrombin-stimulated human platelets, while certain ether phospholipid molecular species become enriched in arachidonate. PMID- 3104717 TI - Helping the stepparent parent. PMID- 3104718 TI - Managing PKU: an update. PMID- 3104719 TI - Breast pump stimulation to promote labor. PMID- 3104720 TI - Neonatal update: surfactant replacement therapy. PMID- 3104721 TI - Evaluating patient learning. PMID- 3104722 TI - Consent for medical treatment. PMID- 3104723 TI - Systematic documentation of practice. PMID- 3104724 TI - Helping children cope with a national disaster. PMID- 3104725 TI - First pregnancy after 35: what is the experience? PMID- 3104726 TI - Responses of small preterm infants to bottle- and breast-feeding. PMID- 3104727 TI - [Program for interpreting acid-base disorders and assessing blood oxygenation]. AB - The paper describes a program for the interpretation of deviations in the acid base state (AAS) and the estimation of the blood oxygenation levels. The program was developed for the Iskra-226 microcomputer and is intended for a direct measurement of the gas composition of the blood. The program makes it possible to calculate the AAS and the blood oxygenation levels (20 parameters), to estimate the AAS deviation type and the degree of its compensation, it accumulates and stores the patient data, keeps records of case histories. PMID- 3104728 TI - Fluorine-19 NMR studies of tumor-bearing rats treated with difluoromethylornithine. AB - Copenhagen rats with implanted metastatic prostate carcinomas have been treated with the drug alpha-difluoromethylornithine (DFMO), an inhibitor of the enzyme ornithine decarboxylase. In vivo and in vitro 19F NMR observations were then carried out on a variety of organs and tissues. The distribution of the drug strongly favored tumor over surrounding muscle. DFMO, which gives a spectrum similar to that of the pH indicator difluoromethylalanine, has potential for determination of in vivo pH. However, in contrast to the alanine analog, DFMO exhibits a considerably smaller shift dependence in response to pH changes. PMID- 3104729 TI - Effects of graded intravenous doses of fructose on glycogen synthase in the liver of fasted rats. AB - We have examined in fasted rats the effects of graded doses of intravenous fructose (50 to 500 mg/kg) in order to determine potential mechanisms by which different concentrations of fructose reaching the liver may modify the activity of glycogen synthase (and phosphorylase). With increasing fructose doses the % synthase I increased threefold to a maximum at a dose of 125 mg/kg and then decreased progressively after higher fructose doses were given. The % phosphorylase a decreased by 30% to a minimum at a dose of 125 mg/kg but increased with higher doses to 370% of the control values. Both the % synthase I and the % phosphorylase a were elevated above the control values at fructose doses of 175 to 225 mg/kg. The increase in % synthase I after low doses of fructose occurred with a significant increase in glucose-6-P but no significant change in hepatic fructose, glucose, UDPglucose, ATP/Mg++, Pi, cAMP, plasma insulin, or glucagon concentrations. The reciprocal decrease in % synthase I and increase in % phosphorylase a occurred despite increases in glucose and glucose-6 P, at fructose doses resulting in no change in ATP/Mg++, Pi or cAMP, and only a small increase (0.39 mmol/L) in the fructose-1-P concentration. We propose that activation of synthase phosphatase by a rise in the glucose-6-P concentration is responsible for the increase in % synthase I after low doses of fructose. The mechanism by which higher fructose doses overcome the expected activation of synthase phosphatase by glucose and glucose-6-P and a decreased ATP/Mg++ ratio is uncertain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104730 TI - Cystine and lysine transport in cultured human renal epithelial cells. AB - The transport of the amino acids, cystine and lysine, was studied in epithelial cell lines propagated from human kidney cortex. Cystine uptake data were reproducible in different cell lines and did not vary over several cell passages of an individual cell line. The transport of this disulfide amino acid was sodium dependent with kinetic analysis showing one apparent Kt system of 0.09 mmol/L and Vmax of 0.054 mmol/L cell water/min. Studies of the kinetics of lysine transport, however, revealed two uptake systems with apparent high and low affinities with Kt of 0.14 mmol/L and 5 mmol/L and Vmax of 0.041 and 0.167 mmol/L cell water/min, respectively. Glutamate appeared to be the most potent inhibitor of cystine uptake by these cultured human renal cells and this interaction was competitive. Although cystine did not inhibit lysine uptake, arginine and ornithine were shown to be major inhibitors, thus providing evidence for the presence of a shared dibasic amino acid transport system. PMID- 3104731 TI - Quenching of the antibacterial activity of chlorhexidine and benzalkonium by Letheen broth and Letheen agar in relation to wild-type and envelope mutant strains of gram-negative bacteria. AB - Letheen broth and Letheen agar have been investigated for their ability to act as neutralising and recovery media for wild-type and envelope mutants exposed to chlorhexidine diacetate and benzalkonium chloride. At high dilutions, untreated cells of the envelope mutant of Pseudomonas aeruginosa 799/61 were unable to produce colonies on Letheen agar. As a result of various procedures, it was concluded that dilution in Letheen broth and plating in Isosensitest agar was a suitable method for quenching cationic bactericides without harming the test strains, and that the increasing use of Gram-negative bacteria with outer membrane defects means that considerable care may be necessary in selecting media for evaluating bactericidal activity. PMID- 3104732 TI - Effects of staphylolytic enzymes from Pseudomonas aeruginosa on the growth and ultrastructure of Staphylococcus aureus. AB - Pseudomonas aeruginosa produces two extracellular staphylolytic enzymes able to lyse Staphylococcus aureus cells when they are added to liquid cultures of S. aureus. In addition, when cultivation was carried out in the presence of both lytic enzymes and 1 M sucrose, the staphylococci either lacked cell walls or showed damaged walls. Lytic activity-resistant cells of S. aureus were also detected. PMID- 3104733 TI - [The effect of catalase added to Lowenstein-Jensen medium on the rate of growth of M. tuberculosis]. AB - In this study, the effect of catalase on the rate of growth Mycobacterium tuberculosis has been investigated. Thirty-five sputa were inoculated on the Lowenstein-Jensen medium and Lowenstein-Jensen medium modified by the addition of catalase 4 mcg/ml. Only four sputa were observed to have an early growth on the Lowenstein-Jensen medium with catalase five days than Lowenstein-Jensen medium. Of the 55 strains grown in the Lowenstein-Jensen medium the following results were obtained from the inoculations made in the Lowenstein-Jensen with catalase and Lowenstein-Jensen medium. At the end of a three week incubation in a medium with 5-10% CO2, a growth of 32 strains (58%) in the Lowenstein-Jensen medium with catalase and a growth of 21 strains (38%) in the Lowenstein-Jensen medium were observed Eleven strains (20%) were observed in the Lowenstein-Jensen medium with catalase and B strains (14%) in the Lowenstein-Jensen medium during the same time in normal atmosphere. PMID- 3104735 TI - [Infection chemoprophylaxis]. AB - It is still not determined exactly that, how and in which conditions infection chemoprophylaxis should be administered. In this review, the situations in which chemoprophylaxis is of proven benefit are discussed. PMID- 3104734 TI - [Escherichia coli, coliform bacteria, Pseudomonas aeruginosa, Proteus and Staphylococcus aureus carriers among children 5-15 years old]. AB - The throat swap cultures of 250 children between 5-15 years ages examined for the microorganisms, E. coli, Coliform, Protus, Ps. aeruginosa and S. aureus. 66 (26.4%) E. coli, 64 (25.6%) S. aureus, 9 (3.6%) Coliform, 3 (1.2%) Ps. aeruginosa, 2 (0.2%) Proteus organisms were isolated from throat swaps cultures of 144 (57.6%) children. 106 (42.4%) children had contained normal oral flora. S. aureus and E. coli strains were tested using disk method for the sensitivity of some antibiotics. S. aureus strains were resistant 12.5% to gentamycin, 9.4% to cefoperazone and (1% to cefazolin, 48.4% to lincomycin and 87.5% to ampicillin. E. coli strains were resistant 42% to gentamycin, 37% to cefoperazone and 74% to cefazolin. PMID- 3104736 TI - Pathophysiological implications of increased brain burden of histamine in protein malnutrition. AB - The complex syndrome of protein-energy malnutrition (PEM) in weanling children, usually complicated by concurrent presence of numerous adverse environmental factors, is a chronic stressful situation which elicits a number of neuroendocrine and metabolic adjustments. Histidine metabolism is severely impaired in PEM in children and in experimental animals, and evidence from the latter indicate markedly increased body burden of histamine. The brain is the organ most prominently affected. Although data are still incomplete, histamine conforms with most criteria required of a neurotransmitter. Histamine interacts with other neuroregulatory substances in modulating many neuroendocrine and vegetative processes. Some of the prominent pathophysiological features associated with PEM in children such as increased circulating cortisol, defective thermoregulation, fluid/electrolyte imbalance, impaired immunity, reduced cardiac output with prolongation of systemic recirculation time, and apathy bordering on a clinical state of depression are consistent with the known effects of histamine as determined by neurochemical and neuropharmacological studies. It is suggested that studies of histamine status in human PEM, and the functional relationships between markedly elevated level of this amine with other neuroregulatory substances, will shed more light on the complex pathogenesis of the nutritional syndrome. PMID- 3104737 TI - Transmucosal controlled-release nitroglycerin. PMID- 3104738 TI - Broad beam and narrow beam attenuation in Lipowitz's metal. AB - Attenuation properties of Lipowitz's metal have been studied for narrow and broad beams of cobalt-60 gamma rays and 4-10 MV x-rays. The measured transmitted fraction for geometries used in radiotherapy depends on the field size and depth of measurement. Therefore a calculation of dose for partially attenuated beams based on narrow beam attenuation coefficients can cause large errors in dosimetry. Our simple calculation of transmitted fractions based on primary attenuation and scattered radiation agrees quite well with the measured data for therapeutic geometries. Also given is a table for linear, mass attenuation, and mass energy absorption coefficients of Lipowitz's metal in the photon energy range from 10 keV to 10 MeV. PMID- 3104739 TI - A comparison of air-cavity inhomogeneity effects for cobalt-60, 6-, and 10-MV x ray beams. AB - The inclusion of air-filled spaces in treatment fields creates a potential dosimetric problem due to the loss of charged particle equilibrium near the air tissue interface. We have used a simulated larynx phantom and a small buildup/extrapolation chamber to compare the magnitude and spatial extent of underdosing and overdosing at the distal surface for two linear accelerators (10- and 6-MV x-rays) and a cobalt-60 machine. Surface doses were compared to doses measured in a similar but homogeneous phantom to give observed/expected ratios (O/E), which were greater than 1.0 for large field sizes and less than 1.0 for small field sizes on all machines. The minimum field sizes which produce no surface underdosing for a simulated 2-cm-diam larynx are roughly 7 X 7 cm for 10 MV x-rays, 6 X 6 cm for 6-MV x-rays, and 5 X 5 cm for cobalt-60. In addition, the depth over which underdosing occurs is seen to increase with increasing energy. PMID- 3104740 TI - Comments on "Buildup/surface dose and exit dose measurements for a 6-MV linear accelerator". PMID- 3104741 TI - Use of fast Fourier transforms in calculating dose distributions for irregularly shaped fields for three-dimensional treatment planning. AB - In three-dimensional radiation treatment planning, essentially all fields are irregular and compensated. Consequently, it is important to predict accurately dose for such fields to ensure adequate coverage of the target region and sparing of healthy tissues. Traditional approaches, namely, those involving scatter integration and extended source and those utilizing negatively weighted fields, are inaccurate, especially near the boundaries defined by blocks and collimators. In the method presented in this paper, dose distributions for arbitrarily shaped beams are calculated by two-dimensional convolution of the relative primary photon fluence distributions and kernels representing the cross-sectional profiles of a pencil beam at a series of depths. The pencil beam dose distributions are computed, once and for all, with the Monte Carlo method for photon energy spectrum for each treatment machine. The finite size of the source, which is important for cobalt machines, is also taken into account using convolution of the source with the relative primary fluence distribution. Convolutions are performed using fast Fourier transforms on an array processor. Results of calculations are in excellent agreement with measured data. While no data are presented for fields modified by compensators, the method of calculation should apply at least as well for such fields since the variations in fluence distribution for compensated fields are not as sharp as for points near the block boundaries. PMID- 3104742 TI - Photon dose perturbations due to small inhomogeneities. AB - An apparatus capable of measuring small fractional changes in ionization current has been used to study the effect of small inhomogeneities on photon dose in water. Small ring-shaped inhomogeneities were introduced into a water phantom and measurements have been made for 4-, 6-, and 18-MV x-rays. The results show beyond the range of secondary electrons, the dose perturbation is basically a photon transport phenomenon which becomes less important as the beam energy increases; within the range of secondary electrons, dose perturbation also involves electron transport, which has a strong dependence on atomic number and could result in a substantially large effect on dose deposition. PMID- 3104743 TI - The extended net fractional depth dose: correction for inhomogeneities, including effects of electron transport in photon beam dose calculation. AB - The extended net fractional depth dose (ENFD) is developed from the net fractional depth dose (NFD) previously described for unit-density media, basically by scaling the two geometric parameters, the side of the equivalent square field, and the depth along the ray by the relative electron density. Specifically, in the analytical description for the NFD, the geometric depth is replaced by the radiologic depth and, along the ray path, the geometric field side is scaled by the relative electron density. Interface effects on the electron and scattered-photon fluences are accounted for. In addition, a simple function is developed to correct for the effect of lateral as well as longitudinal electron transport at the central ray. In the present work the inhomogeneities are assumed to be of planar parallel shape and to extend across the entire beam. The treatment of smaller inhomogeneities is outlined but will be treated in detail separately. Calculated results are compared to measured and calculated data from the literature for 60Co and 10-MV x-rays, and to 15-MV data measured at the NCI. PMID- 3104744 TI - Characteristics of the 6-MV photon beam produced by a dual energy linear accelerator. AB - Clinical dosimetry data are presented for the lower-energy x-ray beam of a Varian Clinac 1800 linear accelerator. This beam has comparable characteristics to single energy linear accelerators with the same stated 6-MV x-ray energy. The nominal beam energy was found to be 5.3 +/- 0.3 MV on the central axis. Beam quality expressed in terms of half-value layer in water was found to vary by less than 10% over the entire field. The surface doses are only slightly, but consistently, larger than those reported in the literature for other 6-MV linacs. Dosimetric results presented include central axis percentage depth dose (% DD) and tissue-maximum ratio (TMR), surface and buildup doses, output factors, and inverse square law applicability. The flatness and symmetry characteristics are within the manufacturer's specifications for both large and small fields. PMID- 3104745 TI - Effect of tissue inhomogeneity on beta dose distribution of 32P. AB - In a homogeneous medium of soft tissue the radiation dose distribution due to a nonuniformly distributed beta source can be calculated by convolution of the beta dose point kernel of the nuclide with the source distribution. A possible extension of the technique to the calculation of the dose distribution in heterogeneous media involving relatively simple geometric interfaces requires the knowledge of the resulting perturbation to the beta point kernels in individual media. We simulated a soft-tissue-bone planar interface by a polystyrene (PST) aluminum junction and measured the change in beta dose from the dose value in homogeneous PST due to a point source of 32P using 7LiF thermoluminescent dosimeters. With the point source at the interface, the dose rates at 0-31, 125 156, and 283-314 mg/cm2 separations from the interface were increased by (12 +/- 3)%, (8 +/- 2)%, and (3 +/- 2)%, respectively, compared with homogeneous PST. With the point source at a PST-air planar interface to simulate a soft-tissue-air junction, the dose rates at 0-31, 139-170, and 283-314 mg/cm2 from the interface were decreased by (25 +/- 4)%, (11 +/- 7)%, and (5 +/- 2)%, respectively. The changes in dose rates for these two interfaces have also been measured with degraded spectra of 32P. Comparison of the experimental data with Monte Carlo calculation for a point source and the two-group method of calculation for a plane source is also presented. PMID- 3104746 TI - [Nutrition in tumor patients]. PMID- 3104747 TI - Photosensory behavior in procaryotes. PMID- 3104750 TI - Intravenous thyrotropin-releasing hormone in patients with amyotrophic lateral sclerosis. Dose-response and randomized concurrent placebo-controlled pilot studies. AB - Focal, small-to-moderate and transient improvement occurred in the muscle strength and function of patients with ALS who received TRH in dose-response and screening studies. In a small pilot study of 12 patients, 3 months administration of TRH at 10 mg per kg on alternate days resulted in localized increased strength of jaw muscles as well as significant improvement in lower extremity function. Aerobic exercise capacity was particularly improved in patients with ALS following administration of TRH. Autonomic effects of TRH on heart rate, respiration, and blood pressure were not serious and attenuated slightly over the course of the study. PMID- 3104751 TI - Intrathecal thyrotropin-releasing hormone in amyotrophic lateral sclerosis. AB - Thyrotropin releasing hormone (TRH) has potential therapeutic applications in amyotrophic lateral sclerosis (ALS) and related diseases because of its function as a neuroregulator of the anterior horn cell. However, its therapeutic potential, and that of other neuropeptides, is reduced by the blood-brain barrier that limits access to neuronal cells. We have thus explored the direct intrathecal administration of TRH in ALS, with both short-term boluses and infusions and chronic constant infusions. Our experience suggests that this approach is safe, has high patient acceptance, and is worthy of more careful evaluation. PMID- 3104752 TI - Observations on the clinical assessment of patients with motor neuron disease. Experience with a TRH analogue. AB - The need for improved assessment techniques in order to monitor the action of substances active in upper and lower motor neuron systems in motor neuron disease is discussed. A long-acting TRH analogue is shown to have detectable acute effects on bulbar symptoms, particularly speech, tone, fasciculations, and muscle force. Endocrine surveillance is essential in studies with TRH and analogues. PMID- 3104753 TI - Neuropsychological perspectives in amyotrophic lateral sclerosis. AB - Three aspects of neuropsychological functioning in patients with ALS are examined. Contrary to previous research, a new psychometric study of psychological adjustment suggested significant depression-distress in this population and related psychological disturbance differentially to signs of upper versus lower motor neuron involvement and to respiratory failure. An association between ALS and impaired neuropsychological functioning is discussed through an examination of the clinical and pathologic literatures. ALS appears to be a multisystem degenerative disease with a variety of expressions that may frequently include loss of cognitive-behavioral competency with progressive involvement of the prefrontal cortex and, in a few instances, profound dementia. Finally, the article describes an analysis of trends in psychological adjustment and in the perception of physical capability over the course of a pilot clinical trial. PMID- 3104749 TI - Nickel utilization by microorganisms. PMID- 3104754 TI - Update on influenza activity worldwide and World Health Organization and United States recommendations for influenza vaccine composition for the 1987-1988 season. PMID- 3104755 TI - Sex-, age-, and region-specific prevalence of sedentary lifestyle in selected states in 1985--the Behavioral Risk Factor Surveillance System. PMID- 3104756 TI - Update: Salmonella enteritidis infections in the northeastern United States. PMID- 3104757 TI - The prevalence of cancer--Connecticut, January 1, 1982. PMID- 3104758 TI - Immunization practices in colleges--United States. PMID- 3104759 TI - Tuberculosis in blacks--United States. PMID- 3104760 TI - Early syphilis--Broward County, Florida. PMID- 3104761 TI - Premature mortality due to sudden infant death syndrome--United States, 1980 1986. PMID- 3104762 TI - Enterically transmitted non-A, non-B hepatitis--East Africa. PMID- 3104748 TI - Methanogens and the diversity of archaebacteria. PMID- 3104764 TI - Behavioral Risk Factor Surveillance--selected states, 1986. PMID- 3104763 TI - Acute hemorrhagic conjunctivitis caused by coxsackievirus A24--Caribbean. PMID- 3104765 TI - Tuberculosis provisional data--United States, 1986. PMID- 3104766 TI - Metal ion inactivation and chelator stimulation of Streptococcus mitis arginine aminopeptidase. AB - Activation of Streptococcus mitis (ATTC 9811) arginine aminopeptidase resulted in removal of the metal(s) from the enzyme molecule, and the action of the heavy metal ion in the inactivation process was shown to involve formation of a chelate complex between the enzyme molecule and metal or oxidation of functional group(s) on the enzyme surface. The enzyme also underwent activation by bovine serum albumin, amino acids, phosphate, and citric acid, which are probable physiological chelators. PMID- 3104768 TI - Microinjection of transforming ras protein induces c-fos expression. AB - Microinjection of p21ras induced c-fos protein accumulation in three types of 3T3 cells. The induction was rapid and efficient and persisted for many hours. In addition, anti-ras antibody dramatically reduced c-fos accumulation after serum stimulation of injected cells. However, cells which expressed p21ras continuously did not maintain a high level of c-fos expression. PMID- 3104767 TI - Regulation of human T-lymphocyte gene expression by interleukin 2: immediate response genes include the proto-oncogene c-myb. AB - Antigen-stimulated human T lymphocytes must bind the immunoregulatory hormone interleukin 2 (IL-2) if they are to transit from the G1 to the S phase of the cell cycle. Indirect methods, such as the measurement of thymidine uptake rates, were previously the only means available for exploring the mechanism of action of IL-2. Several cDNA clones have been isolated which are expressed subsequent to IL 2 binding, and the expression of two of these genes. Tact52 and Tact75, is regulated directly at the level of transcription; expression of the proto oncogene c-myb is also regulated directly by IL-2 binding. These genes thus constitute a set which is coordinately regulated in the course of the transition from G1 to S phase of human T lymphocytes, and their expression depends on IL-2 binding. PMID- 3104769 TI - Organization of the Drosophila melanogaster hsp70 heat shock regulation unit. AB - Expression from the Drosophila melanogaster hsp70 promoter was controlled by a regulatory unit that was composed of two sequence elements that resembled the heat shock consensus sequence. The unit functioned in both orientations and at different distances from downstream promoter sequences. Each element of the unit alone was essentially inactive. Association of two elements resulted in a dramatic increase of transcription from the hsp70 promoter. This synergistic effect was independent of the relative orientation of the elements and, to a large extent, of the distance between them. Duplication of a region containing only one element also yielded a highly active, heat-regulated promoter. Genes with three to five elements were three to four times more active than those with a single regulatory unit. PMID- 3104770 TI - Kinds of mutations formed when a shuttle vector containing adducts of benzo[a]pyrene-7,8-diol-9,10-epoxide replicates in COS7 cells. AB - We have investigated the kinds of mutations induced when a shuttle vector containing covalently bound residues of the (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) replicates in the monkey kidney cell line COS7. The target for detecting mutations was the 200-base pair gene for a tyrosine suppressor tRNA (supF), inserted at the EcoRI site in shuttle vector p3AC (Sarkar et al., Mol. Cell. Biol. 4:2227-2230, 1984). When introduced by transformation, a functioning supF gene in progeny plasmid recovered from COS7 cells allows suppression of a lacZ amber mutation in the indicator Escherichia coli host. Treatment of p3AC with BPDE caused a linear increase in the number of BPDE residues bound per plasmid. Untreated plasmids and plasmids containing 6.6 BPDE residues were transfected into COS7 cells, and the progeny were assayed for mutations in the supF gene. The frequency of mutants generated during replication of the BPDE-treated plasmids was not higher than that from untreated plasmids, but the two populations differed markedly in the kinds of mutations they contained. Gel electrophoresis analysis of the size alterations of 77 mutant plasmids obtained with untreated DNA and 45 obtained with BPDE-treated DNA showed that the majority of the mutant progeny of untreated plasmids exhibited gross alterations, principally large deletions. In contrast, the majority of the mutants generated during replication of the BPDE-treated plasmids contained only minor alterations, principally point mutations. Sequence analysis of progeny of untreated plasmids containing putative point mutations showed insertions and deletions of bases and a broad spectrum of base substitutions; in those from BPDE-treated plasmids, all base substitutions involved guanosine . cystosine pairs. PMID- 3104771 TI - The ovarian, ecdysterone, and heat-shock-responsive promoters of the Drosophila melanogaster hsp27 gene react very differently to perturbations of DNA sequence. AB - The effect of various types of DNA sequence alterations on the activity of the ovarian, ecdysterone, and heat-shock-responsive promoters of the Drosophila melanogaster hsp27 gene was studied by P element-mediated germ line transformation. Regions of DNA required for proper expression of the gene under these different conditions were identified. Wild-type levels of transcription during oogenesis are dependent on two elements respectively located within a 64 base-pair (bp) fragment in the transcribed untranslated region and between -227 and -958 bp upstream of the transcription start site. This ovarian expression is particularly sensitive to both chromosomal position effects and an increased distance between the distal upstream promoter element and the TATAA homology. The ecdysterone-mediated expression during metamorphosis is dependent on a 145-bp domain including the TATAA box and additional upstream sequences that augment transcription by two- to five-fold. Finally, sequences necessary for heat shock expression are located much further upstream from hsp27 than those previously found for hsp70, although basal expression was correlated with the presence of more proximal heat shock consensus sequences. PMID- 3104773 TI - [Proteins induced by the double-stranded interferon inducer poly(I).poly(C)]. AB - The possible pathways for realization of antiviral activity of interferon inducer poly (I).poly(C) have been studied. The stimulating effect of interferon inducer on the net protein synthesis in human M19 fibroblasts has been demonstrated. Compositions of the specific proteins induced by poly(I).poly(C) or interferon in human M19 fibroblasts and in monkey cells 4647 have been analyzed by electrophoresis technique. The data obtained suggest the existence of common gene products for interferon and ds-inducer. The ds-inducer requires the synthesis of lesser amounts of proteins for realization of its biological activity as compared with interferon. PMID- 3104772 TI - Positive regulation of the beta-galactosidase gene from Kluyveromyces lactis is mediated by an upstream activation site that shows homology to the GAL upstream activation site of Saccharomyces cerevisiae. AB - In contrast to the Escherichia coli lac operon, the yeast beta-galactosidase gene is positively regulated. In the 5'-noncoding region of the Kluyveromyces lactis LAC4 gene, we mapped an upstream activation site (UAS) that is required for induction. This sequence, located between positions -435 and -326 from the start of translation, functions irrespective of its orientation and can confer lactose regulation to the heterologous CYC1 promoter. It is composed of at least two subsequences that must act in concert. One of these subsequences showed a strong homology to the UAS consensus sequence of the Saccharomyces cerevisiae GAL genes (E. Giniger, S. M. Varnum, and M. Ptashne, Cell 40:767-774, 1985). We propose that this region of homology located at about position -426 is a binding site for the product of the regulatory gene LAC9 which probably induces transcription of the LAC4 gene in a manner analogous to that of the GAL4 protein. PMID- 3104774 TI - [Transfecting activity of Pseudomonas aeruginosa bacteriophage SM]. AB - Factors affecting the efficiency of transfection of Ps. aeruginosa PAO1 cells by the temperate SM bacteriophage DNA have been determined. The efficiency of transfection by DNA preparations isolated from the wild type bacteriophage SMc+ or its thermoinducible mutant SM cts6 is practically the same. The frequency of transfection is (7-9) X 10(4) of infectious centers per mkg of transfecting DNA. Variability in the frequencies of transfection has been registered depending of the infection conditions or on the transfer of the Ps. aeruginosa PAO1 recipient strain population into the competence phase. The efficiency of transfection is increased by the addition of Ca2+ or Mg2+ ions affecting the adsorption and absorbtion of phage DNA by the recipient cells. Optimal concentrations of the bivalent metal ions are 0.15M CaCl2 and 0.2M MgCl2. The results obtained have been used for optimizing the conditions of Ps. aeruginosa PAO1 transfection by SM bacteriophage DNA. PMID- 3104775 TI - Inhibitory effect of phenolic compounds on aflatoxin B1 metabolism and induced mutagenesis. AB - The interaction between phenolic compounds and the food-borne carcinogenic mycotoxin, aflatoxin B1 (AFB1), was examined. 6 phenolic compounds (gallic acid, chlorogenic acid, caffeic acid, dopamine, p-hydroxybenzoic acid and salicylic acid) inhibited AFB1-induced mutagenesis in Salmonella typhimurium strain TA98 in a suspension assay in the presence of rat-liver microsomes (S9). The inhibitory effect was observed when the phenolic compound and the mutagen (AFB1 plus S9) were administered concurrently, but not when exposure to the mutagen was followed by the phenolic compound. The concentrations of the phenolic compounds used were not mutagenic to S. typhimurium strain TA98 and had no effect on the survival of the bacteria. The inhibition of AFB1 metabolism was studied using high-pressure liquid chromatography. Increasing the concentration of all 6 phenolic compounds resulted in a dose-dependent reduction of both major AFB1 metabolite peaks. The results are consistent with the hypothesis that the phenolic compounds do not react covalently with AFB1, and the inhibitory effect of phenolic compounds on AFB1-induced mutagenesis may be due to the inhibition of the activation enzymes. PMID- 3104776 TI - Patterns of epoxide metabolism by epoxide hydrolase and glutathione S-transferase associated with age and genotype in Drosophila melanogaster. AB - Epoxide hydrolase and glutathione S-transferase activities toward trans- and cis stilbene oxides were measured in 3 strains of Drosophila melanogaster. Differences in age dependence, substrate selectivity and subcellular location were detected suggesting the presence of multiple forms of these enzymes. In addition, interstrain differences indicate the presence of genetic variation for epoxide hydrolase and glutathione transferase activities. These results illustrate a potential use of these assays in D. melanogaster to complement existing tests (e.g. recessive lethal tests or Ames assays) for evaluating the relationship between epoxide hydrolase and glutathione S-transferase levels and the genotoxicity of epoxides. PMID- 3104777 TI - Internal standards for survival: increasing the accuracy for human cell mutation assays. AB - In mutation and cell transformation assays, it has long been recognized that the common practice of using different numbers of cells on dishes with or without selective conditions creates a source of bias in mutant fraction determination. This is simply because colony formation may be enhanced or suppressed at higher initial cell densities, depending on the assay and agent tested. We propose a solution that consists of the inclusion of an experimentally distinguishable population of cells as an internal standard for colony-forming ability at the high cell density required for detection of rare variants. This method is found to be highly satisfactory for use in measuring mutation to 6-thioguanine resistance in a diploid human B lymphoblast line. For treatment with anti-2,3 dihydroxy-1,10b-epoxy-1,2,3-trihydrofluoranthene (FDE), N-methyl-N'-nitro-N nitrosoguanidine (MNNG), and 4-nitroquinoline-oxide (4NQO), the calculated induced mutant fractions using the internal-standard method were significantly lower than those calculated using the conventional low-density-plating efficiency method. The results of these experiments and our analysis lead us to conclude that this approach is applicable to all single cell mutation or transformation assays and is a necessary feature of assays in which an accurate knowledge of the fraction of rare variants is required. PMID- 3104778 TI - Bio-antimutagenic effect of L-cysteine on diiodohydroxyquinoline-induced micronuclei in Swiss mice. AB - The mutagenic potential of diiodohydroxyquinoline (DIHQ), a common anti-amebic drug, was tested using the in vivo micronucleus test in Swiss mice following oral administration. It was found to be mutagenic in a dose-dependent manner. Using the same model system, the bio-antimutagenic effect of the sulfhydryl compound L cysteine against DIHQ was established. PMID- 3104780 TI - Sudden infant death syndrome continues to baffle researchers. PMID- 3104779 TI - Induction of unscheduled DNA synthesis in liver and micronucleus in bone marrow of rats exposed in vivo to the benzidine-derived azo dye, Direct Black 38. AB - The genotoxic activity of the benzidine-derived azo dye, Direct Black 38 (DB38), was studied in vivo, using two different genetic end-points: unscheduled DNA synthesis in liver (UDS) and bone marrow micronucleus (MN). Exposure times were 12, 24 or 36 h. Both assays were performed in the same rat, except for the 24-h exposure when only MN was investigated. For the liver UDS assay, the rat hepatocarcinogen, 6-dimethylaminophenylazobenzthiazole (6BT), was used as positive control and for the MN assay, cyclophosphamide (CP). In agreement with earlier results, 6BT gave rise to a dose-related increase in liver UDS after 12-h exposure to 25 or 50 mg/kg bw. After 36-h exposure, there was still an indication of a weak dose-response effect between 0 and 5 net nuclear grains (NG). DB38 induced liver UDS at the higher dose levels used (500 and 1000 mg/kg), and after both 12- and 36-h exposure. With the longer exposure time, a weak induction of UDS was also observed at 100 mg/kg. The strongest UDS induction (12.2 NG), was obtained in one rat after 36-h exposure to 500 mg/kg. DB38 also had a weak effect on the MN induction, which was statistically significant at the higher concentrations used. A dose-related response was observed at all exposure times used. PMID- 3104782 TI - Baby's biological clock may have implications for parents and health-care providers. PMID- 3104781 TI - SIDS project offers delactation advice. PMID- 3104783 TI - Faculty and students establish prenatal clinic. PMID- 3104784 TI - Ethics and patient advocacy in nursing research. PMID- 3104786 TI - Member hails collaborative practice. PMID- 3104785 TI - A matter of policy. PMID- 3104787 TI - Antimicrobial prophylaxis in surgery. PMID- 3104788 TI - Prevalence of paracoccidioidomycosis in hospitalized adults in Rio de Janeiro (RJ) Brazil. AB - Double immunodiffusion were used as screening test for the diagnosis of paracoccidioidomycosis. Five hundred hospitalized adults from general (150 patients--group I) and from a specialized chest disease hospital (350 patients- group II), were tested. All of them were without definitive etiological diagnosis and clinical specimens were obtained from the patients with positive serology. Testing sera obtained from 150 patients of the group I, fifty six cases of paracoccidioidomycosis were diagnosed. Specimens for mycological examination were subsequently obtained from 50 of these patients; P. brasiliensis could be recovered in 49 (98%). Fundamental importance was the finding of 17 (4.8%) cases of paracoccidioidomycosis among the 350 patients referred from a chest disease hospital (group II). Serological evidence of paracoccidioidomycosis found in 73 (14.6%) of the 500 screened patients, indicates a relatively high prevalence of this mycosis in adults patients admitted to several hospitals in RJ. These data probably do not reflect the real prevalence of paracoccidioidomycosis in RJ and should be considered as a gross underestimation. Thus, attention should also be paid to juvenile forms and DID could be of a great value in screening these cases too. PMID- 3104789 TI - Nomenclature of immunological markers. PMID- 3104790 TI - Somatic hypermutation of an immunoglobulin transgene in kappa transgenic mice. AB - Initial studies of somatically acquired mutations in immunoglobulin V regions from hybridomas and myelomas that are not derived from joining aberrations, suggested a controlled and specific hypermutation process, because spontaneous mutation rates observed for other genes are extremely low. Some evidence for the idea that mutations are introduced during V-gene rearrangement came from the clustering of mutations at the joining sites, from the absence of mutations in unrearranged V genes and from the low level of mutations in only partially (D-J) rearranged nonproductive heavy-chain alleles. Another model in which mutations accumulate with each cell division, rather than being introduced all at once, was supported by the finding that immunoglobulin genes of hybridomas derived from a single mouse frequently had several mutations in common, and so might be derived from the same precursor cell whose daughters then accumulated additional mutations. But the common mutations in some cases could be due to as yet unidentified related germline genes, or could represent the effect of antigen selection for certain amino acids. To try to detect hypermutation in the absence of V-gene rearrangement, we isolated B lymphocytes with endogenous heavy-chain gene mutations from transgenic mice carrying pre-rearranged kappa-transgenes. We found that these kappa-transgenes were also somatically mutated. This and other observations indicated that: ongoing rearrangement is not required for mutation; there are signals for hypermutation in the transgenes; the mutations are found only in the variable region, so the constant region may not be a target; different transgene insertion sites are compatible with hypermutations and more than one transgene is expressed in the same cell. PMID- 3104791 TI - Structure of a mutant of tyrosyl-tRNA synthetase with enhanced catalytic properties. AB - One surprising outcome of applying the techniques of protein engineering to the enzyme tyrosyl-transfer RNA synthetase was that the enzyme's activity could actually be increased by a specific sequence change. In particular, altering residue threonine 51 to a proline (mutant TP51) increased the enzyme's affinity for tyrosyl adenylate complexes. The non-additive effect of combining the TP51 mutation with a second sequence alteration (histidine 48 to a glycine) suggested that the effect of the TP51 change might be mediated by a structural change involving the peptide backbone. To address the question of the mechanism by which the TP51 change increases the activity of tyrosyl-tRNA synthetase we have determined the structure of the mutant enzyme. We find the change has a purely local effect on the structure of the enzyme, and conclude that the increased activity of the TP51 mutant probably results from the replacement of the polar threonine residue by a non-polar group: in the wild-type enzyme substrate binding is disfavoured by the displacement of solvent from the vicinity of threonine 51. This unfavourable effect is absent in the TP51 mutant. PMID- 3104792 TI - Food for thought. PMID- 3104793 TI - Archaeology: a Neolithic way of death. PMID- 3104794 TI - Patterns and rates of enamel growth in the molar teeth of early hominids. AB - A recent study of the surface manifestation of incremental lines associated with enamel formation suggested that the crowns of early hominid incisor teeth were formed more rapidly than those of modern humans. In the absence of comparative data, the authors were forced to assume that enamel increments in fossil teeth were similar to those in modern humans. We have used evidence from the fractured surfaces of molar teeth to deduce estimates for both long- and short-period incremental growth markers within enamel in east African 'robust' australopithecine and early Homo teeth. We conclude that in these early hominids, crown formation times in posterior teeth, particularly in the large thick enamelled molar teeth of the east African 'robust' australopithecines, were shorter than those of modern humans. This evidence, considered together with data on crown and root formation times in modern apes, suggests that the posterior teeth in these hominids both formed and erupted more rapidly than those of modern man. These results have implications for attempts to assess dental and skeletal maturity in hominids. PMID- 3104796 TI - Variations of AIDS virus relatives. PMID- 3104795 TI - Thy-1-mediated T-cell activation requires co-expression of CD3/Ti complex. AB - In addition to monoclonal antibodies against the CD3 (T3)-T-cell antigen receptor (CD3/Ti) complex, several other monoclonals directed towards distinct cell surface structures on human (CD2 (T11) and Tp44) and murine (Thy-1, TAP, and Ly 6) T lymphocytes are capable of activating T cells. It has been proposed that such structures may function as alternative pathways of stimulation. To examine directly whether any relationship exists between Thy-1-dependent activation phenomena and T-cell activation mediated through the CD3/Ti complex, we have transfected several CD3/Ti- variants of the human T-cell line Jurkat with the murine Thy-1.2 gene. Our data indicate that in CD3/Ti-, Thy-1.2+ transfectants, monoclonal antibodies against Thy-1.2 can induce a rise in cytoplasmic free calcium ([Ca2+]i), but fail to stimulate interleukin-2 (IL-2) production. The only defect in these variant cell lines responsible for the inability to produce IL-2 in response to Thy-1 stimulation was in the expression of the CD3/Ti complex, because replacement of defective Ti alpha- or beta-chain genes reconstributed both surface expression of CD3/Ti and responsiveness to Thy-1 in the IL-2 production assay. PMID- 3104798 TI - Conservation biology: living Latin binomials. PMID- 3104797 TI - Cloning of HTLV-4 and its relation to simian and human immunodeficiency viruses. AB - Although much is now known of the strain variation among the type-1 human immunodeficiency virus (HIV-1), which is the cause of AIDS (acquired immune deficiency syndrome) in the United States, Europe, and Central Africa, much less is yet known about a second group of viruses that have been found in West Africans. One member of this group, named human T-cell lymphotropic virus type 4 (HTLV-4), has been isolated from healthy Senegalese. Another is the virus isolated from West Africans with AIDS-like illness and originally called LAV-2 but now renamed HIV-2. Both these viruses seem to be less closely related to HIV 1 than they are to a virus of healthy African green monkeys, known variously as simian T-cell lymphotropic virus type 3 (STLV-3) or simian immunodeficiency virus (SIV), which in turn is related to viruses isolated from healthy sooty mangabeys and captive macaques with a form of immunodeficiency (to distinguish these viruses they are referred to as STLV-3 (or SIV)agm, STLV-3mac, or STLV-3smm). To clarify the relationship between the various HIVs, STLV-3s and HTLV-4 we are determining and comparing the molecular and biological characteristics of several of them. Following our recent publication of a restriction-site map of STLV-3agm, we now report that the equivalent map of three isolates of HTLV-4 is remarkably similar to it. In addition we present comparative sequence data on the long terminal repeats (LTR) of HTLV-4, STLV-3agm, HIV-1 and HIV-2, together with evidence that cloned HTLV-4 uses the same receptor as HIV-1 and induces some, but not all, of the cytopathic effects attributed to most isolates of HIV-1 and HIV 2. PMID- 3104799 TI - Synapsin I and the cytoskeleton. PMID- 3104800 TI - Synapsin I bundles F-actin in a phosphorylation-dependent manner. AB - Synapsin I is a neuron-specific phosphoprotein localized to the cytoplasmic surface of synaptic vesicles. This phosphoprotein is a major substrate for cyclic AMP-dependent and calcium/calmodulin-dependent protein kinases. Its state of phosphorylation can be altered both in vivo and in vitro by a variety of physiological and pharmacological manipulations known to affect synaptic function. Recent direct evidence suggests that it may be involved in the regulation of neurotransmitter release from the nerve terminal. In the nerve terminal, synaptic vesicles are embedded in a cytoskeletal network, consisting in part of actin. We report here the ability of the dephospho-form of synapsin I to bundle F-actin. This bundling activity is reduced when synapsin I is phosphorylated by cAMP-dependent protein kinase and virtually abolished when it is phosphorylated by calcium/calmodulin-dependent protein kinase II or by both kinases. These results, demonstrating an interaction of synapsin I with actin in vitro, support the possibility that synapsin I is involved in clustering of synaptic vesicles at the presynaptic terminal and that the phosphorylation of synapsin I may be involved in regulating the translocation of synaptic vesicles to their sites of release. PMID- 3104801 TI - Evaluating cost-effectiveness of preevaluation client contacts. PMID- 3104803 TI - [National mortality and the cost of health care]. PMID- 3104802 TI - State case mix systems for reimbursement long-term care for the elderly. PMID- 3104804 TI - [Brain death, a continuing discussion?]. PMID- 3104805 TI - [Percutaneous endoscopic gastrostomy]. PMID- 3104806 TI - Mitomycin C induced chromosomal aberrations and sister chromatid exchanges (SCEs) in lymphocytes of patients with precancerous and cancerous lesions of the uterine cervix. AB - Baseline and mitomycin C (MMC)-induced chromosomal aberrations and sister chromatid exchanges (SCEs) in blood lymphocytes of patients with cervical precancerous and cancerous lesions and normal women were studied. The baseline frequency of chromosomal aberrations and SCEs revealed a significant increase in higher grades of precancerous (moderate and severe dysplasias) and cancerous lesions compared to those of controls. The MMC-induced chromosomal aberrations and SCEs did not show any differential response in the different groups studied. The results thus indicate that chromosomal instability as observed in precancerous and cancerous lesions is not associated with their sensitivity to mitomycin C. PMID- 3104807 TI - Lactic acid concentration and acid-base balance in cerebrospinal fluid: observations of diagnostic importance in non-Hodgkin lymphoma. AB - Measurements of lactic acid concentration and gas analysis were performed in lumbar cerebrospinal fluid from 36 patients without malignant central nervous system involvement and four patients with meningeal dissemination of non-Hodgkin lymphoma. The upper lactic acid concentration in controls of 2.48 mmol/l was exceeded in all four patients, also in cases with low blast counts and normal protein and glucose content. The pH, pCO2, pO2 and standard bicarbonate concentration in spinal fluid of patients with meningeal dissemination in non Hodgkin lymphoma did not show significant differences compared with other patients and controls. Determination of the lactic acid concentration in cerebrospinal fluid add information, relevant to the diagnosis of meningeal involvement in non-Hodgkin lymphoma. PMID- 3104808 TI - Biochemical markers of malignant melanoma. AB - The excretion of Thormahlen positive melanogens (TPM), zincuria, serum dopaoxidase activity of tyrosinase and serum sialic acid were determined in 60 patients with primary and/or metastatic cutaneous melanoma and in 20 healthy persons. On the basis of our results we can recommend the following of TPM urinary excretion and serum dopaoxidase activity in the course of malignant melanoma as specific markers of the tumor growth. The following of serum sialic acid in the course of malignant melanoma is valuable from the standpoint of prognosis of the disease. The following of zincuria in the course of malignant melanoma is not recommended because of its low value for monitoring melanoma patients. PMID- 3104809 TI - Peptide and steroid hormone levels in pre- and postmenopausal breast carcinoma. AB - Circulating levels of LH, FSH, prolactin, estradiol, progesterone and testosterone were measured by radioimmunoassay in 15 premenopausal (PR-M) age matched healthy controls, 35 premenopausal breast cancer patients prior to therapy, 20 postmenopausal (PO-M) age matched healthy controls and 68-71 postmenopausal breast cancer patients prior to therapy. The patients had histologically proven breast cancer. In PR-M breast cancer group, the LH and progesterone did not differ significantly whereas prolactin showed marked elevation (p less than 0.001) and estradiol and testosterone showed significant decrease (p less than 0.001). The PO-M breast cancer patients exhibited remarkable increase in the levels of LH, FSH, prolactin and testosterone (p less than 0.001) whereas estradiol and progesterone showed little increase in the levels (p less than 0.2 and less than 0.1, respectively). From the results, it is concluded that prolactin and altered ratio of estrogen and androgen plays a major role in the genesis of breast cancer. PMID- 3104810 TI - Altered structural proteins in plaques and tangles: what do they tell us about the biology of Alzheimer's disease? AB - The progressive dysfunction and loss of neurons in Alzheimer's disease (AD) is accompanied by marked structural changes in innumerable neuronal cell bodies and neurites, particularly in limbic and association cortices. Qualitatively indistinguishable neuronal lesions occur in much smaller numbers during normal aging. Highly insoluble paired helical filaments (PHF) and antigenically related straight filaments accumulate in perikaryal tangles and the neurites of neuritic plaques. In addition, PHF antibodies reveal the presence of PHF antigens in many individual cortical neurites not clustered into discrete plaques. Recent studies in several laboratories indicate that altered forms of the microtubule-associated phosphoprotein, tau, are important constituents of PHF. Other neuronal cytoskeletal proteins, particularly microtubule-associated protein 2 and neurofilament, have also been associated with PHF. In contrast, the extracellular amyloid filaments found in the centers of many neuritic plaques and in cortical and meningeal vessels appear to be composed of hydrophobic low molecular weight protein(s) distinct from PHF. A major question for further study regards the cellular origin and role of microvascular amyloid in the degeneration of neurites of multiple neurotransmitter specificities in AD cortex. The widespread neuritic and perikaryal alterations in brain tissue are likely to represent, at least in part, the morphological substrate of cortical dysfunction in AD. PMID- 3104812 TI - [Anterior subtotal somatectomy for multi-level spondylosis and ossification of the posterior longitudinal ligament]. PMID- 3104811 TI - Cerebral oxygen consumption and blood flow in Fischer-344 rats of different ages. AB - Regional cerebral oxygen consumption and blood flow were determined and compared in conscious male Fischer-344 rats at 3, 12, 24 and 33 months of age to correlate the reported regional neurochemical and morphological changes which occur in these parameters during development, maturation, aging and senescence. Cerebral blood flow was determined with 14[C]-labelled iodoantipyrine and regional cerebral arterial and venous oxygen saturation was measured microspectrophotometrically. Oxygen consumption was obtained by multiplying cerebral blood flow and oxygen extraction. Systolic and diastolic blood pressure and heart rate decreased significantly with age. Average cerebral blood flow, oxygen extraction and oxygen consumption/100 g did not differ significantly between the four age groups examined. Oxygen consumption averaged 2.9 +/- 0.1 ml O2/min/100 g (mean +/- S.E.M.) in the 3-month-old group and 3.6 +/- 0.1 ml O2/min/100 g in the 33-month-old group. Differences in flow among the examined brain regions, which were present in the mature, 12-month-old brain, were not present in the developing, aging or senescent rat brain. Compensatory alterations in the efficiency or organization of neurochemical activity which occur during development, aging and senescence may modify the inter-regional differences in cerebral blood flow and oxygen consumption noted during maturation. There was no correlation found between the neurochemical and morphological changes which have been reported during maturation, aging or senescence and regional cerebral oxygen consumption. PMID- 3104813 TI - Selective tolerance of group III and IV somatosympathetic reflexes to the effects of alfentanil. AB - The effect of alfentanil on responses in renal sympathetic nerves evoked by supramaximal electrical stimulation of the radial nerve, has been observed in 6 dogs anaesthesized with alpha-chloralose, paralysed with suxamethonium and ventilated artificially. During an initial infusion of alfentanil the responses of the late group IV (C fibre) and early group III (A delta) were abolished by mean doses of 68 micrograms kg-1 (SEM 3.2 micrograms kg-1) and 797 micrograms kg 1 (SEM 120 micrograms kg-1), respectively. Recovery was allowed to occur to approximately 50% of control values (mean time 76 +/- 14.3 min). The preparations were then conditioned with 7 incremental doses from 7.5 to 120 micrograms kg-1 (i.v.) (total dose 308.5 micrograms kg-1), administered at intervals of 10 min, and subsequently tested with large bolus doses (up to 2000 micrograms kg-1) of alfentanil. In two preparations, the responses of both group IV and group III became completely tolerant to the effects of alfentanil while in the other four the response of the group IV was still eliminated by the drug and the response of group III showed selective tolerance. The heart rate and arterial pressure were reduced by 45 and 29%, respectively during the initial infusion of alfentanil. Thereafter there were no further significant changes in the circulation until the administration of naloxone (2 mg i.v.), which restored the sympathetic responses, heart rate and arterial pressure to control values. PMID- 3104814 TI - Interaction between thyrotropin-releasing hormone and the mesolimbic dopamine system. AB - The involvement of the mesolimbic dopamine (DA) system in the excitatory behavioral effects of thyrotropin-releasing hormone (TRH) has been a controversial topic. In this study TRH was injected into the nucleus accumbens, lateral ventricles or ventral tegmental area and changes in spontaneous motor activity and metabolism of DA in the nucleus accumbens and striatum measured. Injection of TRH into all three areas of the brain produced an increase in photocell counts of locomotor activity and, in the nucleus accumbens, a significant decrease in photocell counts of rearing was measured. Injection of TRH into the nucleus accumbens caused a marked increase in metabolism of DA in both the nucleus accumbens and striatum. A smaller increase in metabolism of DA was also observed after injection of TRH into the lateral ventricles, but no significant change was found after intra-ventral tegmental administration of TRH. These data indicate that while TRH probably acts in the nucleus accumbens to enhance the metabolism of DA, and presumably release of DA, the excitatory behavioral effect of TRH is only partially mediated by this dopaminergic mechanism. PMID- 3104815 TI - Behavioural and electrocortical spectrum power effects of growth hormone releasing factor in rats. AB - The effects on behaviour and electrocortical spectrum power of intracerebroventricular, intrahippocampal and intracaudate injections of human pancreatic growth hormone releasing Factor-40 (hpGRF) (10-100 ng) were studied in rats. The hpGRF, given into the third cerebral ventricle or into the dorsal hippocampus (50-100 ng), in freely-moving rats, produced behavioural sedation accompanied by electrocortical synchronization and an increase in the total voltage power with a predominant increase in the lower frequency bands. On the contrary, unilateral injection of hpGRF (75 ng) into the head of the caudate nucleus produced an increase in locomotor activity, marked postural changes, episodes of contralateral circling and an intense pattern of stereotyped movements. In all, these results indicate that, besides its specific endocrinological effects, hpGRF possesses, in small doses, marked behavioural and electrocortical actions, the mechanism(s) of which still remain to be elucidated. PMID- 3104816 TI - High affinity specific binding of the thyrotrophin releasing hormone metabolite histidylproline to rat brain membranes. AB - Histidylproline a metabolite of Thyrotrophin Releasing Hormone specifically binds to both high and low affinity sites in fresh rat brain membranes. Characterisation of the high affinity site under optimal conditions demonstrated an equilibrium dissociation constant (KD) of approximately 9nM and maximum binding capacity of approximately 120 fmols/mg protein. Kinetic analysis of [3H] His-Pro binding is limited by low binding density, instability of the high affinity site and rapid degradation of the radioligand. The thiol blocking reagent pHydroxymercuriphenylsulphonic acid (HMPS) inhibited [3H]-His-Pro degradation but also reduced binding of the peptide to membranes. The results are discussed with reference to the lack of specific binding sites in brain for the proposed neuropeptide and TRH metabolite cyclo(His-Pro). PMID- 3104817 TI - Experimental carbon dioxide laser brain lesions and intracranial dynamics: Part 3. Effect on cerebral blood flow. AB - Experimental carbon dioxide brain lesions were created over the intact dura mater of the left parietooccipital region of the anesthetized albino rabbit (40-watt impacts of 0.5-second duration, for a total of 4 seconds, with 0.5-second intervals between impacts), and cerebral blood flow (CBF) studies were performed with the hydrogen clearance technique. The animals were mechanically ventilated to maintain a constant PaCO2. Blood pressure, central venous pressure, electroencephalogram, and intracranial pressure were continuously monitored. The control CBF before lesion was 64.1 +/- 15.8 and 70.9 +/- 13.4 ml/100 g/minute for the left and the right hemispheres, respectively. CBF studies at 2, 4, 6, 8, and 24 hours after the lesion did not significantly change from the control values, save for a trend to increase over the right hemisphere only at 2 hours (range 106.0 +/- 55.4 to 41.6 +/- 9.3). It is concluded that in this model the changes in intracranial pressure and brain edema that are seen and have been previously reported are not due to change in cerebral circulation. The brain edema that results probably has characteristics similar to those seen in the cryogenic lesion (vasogenic) model, and this could account for the rise in intracranial pressure. PMID- 3104818 TI - An epileptic syndrome caused by mesial frontal lobe seizure foci. AB - We describe an epileptic syndrome of bilaterally coordinated limb movements, axial movements, vocalization, and nonmasticatory oral activity. EEG and physiologic evidence indicates the syndrome is caused by ictal discharge in the mesial frontal lobes. Two of 12 patients were not helped by anterior temporal lobectomy, and 3 others improved after section of the anterior two-thirds of the corpus callosum. PMID- 3104819 TI - Pharmacokinetics of intrathecal thyrotropin-releasing hormone. AB - An investigation of the efficacy of thyrotropin-releasing hormone in amyotrophic lateral sclerosis included study of the intrathecal pharmacokinetics of this neuropeptide. Its mean elimination half-life in CSF was 0.90 hours and was monoexponential. During a 2-hour infusion, 2.75% crossed the CSF/blood-brain barrier. Infusion for 12 months with an implanted pump in three patients at a rate of 3 mg/24 hr resulted in a mean CSF steady state of 2.88, 2.42, and 2.74 micrograms/ml, respectively. Pharmacokinetic data were similar at 6 and 12 months. This is an effective system with potential uses in the treatment of other degenerative diseases. PMID- 3104820 TI - Treatment of amyotrophic lateral sclerosis with the TRH analog DN-1417. AB - Thyrotropin-releasing hormone has been reported to increase strength in patients with amyotrophic lateral sclerosis (ALS). DN-1417 is an analog of thyrotropin releasing hormone, which has less endocrinologic activity, but more anterior horn cell stimulating effect (with no "autorefractory state"). However, 2 mg DN-1417, IM twice a day for 1 month in an open-label trial, produced no objective improvement of strength in nine patients with ALS. No patient entered the double blind, placebo-controlled phase of the trial. PMID- 3104821 TI - Prolactin response in PD. PMID- 3104822 TI - AIDS. Case for diagnosis, 1987. PMID- 3104823 TI - Mortality of Australian veterans of the Vietnam Conflict and the period and location of their Vietnam service. PMID- 3104824 TI - A practical review of obesity in military medicine. PMID- 3104825 TI - Selected reserve-civilian hospital collaborative training: Naval Reserve Naval Hospital Portsmouth 1305 and Grant Medical Center. PMID- 3104826 TI - U.S. Navy special psychiatric rapid intervention team (SPRINT). PMID- 3104827 TI - An aid to temporary staffing shortages: the nursing pool. PMID- 3104828 TI - Comparison of accident rates among departments of a Veterans Administration Medical Center (1981-1984). PMID- 3104829 TI - Lack of prevention of adhesion formation following tubal microsurgery in the rabbit. PMID- 3104830 TI - Third molars and acute pericoronitis: a military problem. PMID- 3104831 TI - The use of the Durnin-Womersley generalized equations for body fat estimation and their impact on the Army Weight Control Program. PMID- 3104832 TI - Removal of bacteria from blood. PMID- 3104833 TI - Case for diagnosis. Bronchial carcinoid, metastatic to the mandible. PMID- 3104834 TI - Predeposit autologous blood: a valuable resource for military blood banks. PMID- 3104835 TI - [Physiopathology of pancreas transplantation with reference to endocrine function and rejection]. PMID- 3104836 TI - Thyrotropin-releasing hormone (TRH)-immunoreactive boutons and nerve cell bodies in the dorsal horn of the cat L7 spinal cord. AB - With the use of the peroxidase-anti-peroxidase (PAP) technique, thyrotropin releasing hormone (TRH)-like immunoreactivity was found in axon terminals and cell bodies in the dorsal horn of the cat spinal cord L7 segment. In particular, a conspicuous band-shaped region of axon terminals was observed in laminae II and III, while the cell bodies were most frequent in lamina III. Electron microscopic analysis showed that the TRH-immunoreactive terminals made synaptic contacts with cell bodies and dendrites of various sizes. PMID- 3104837 TI - Diversity in neurohaemal organs for homologous neurosecretory cells in different insect species as demonstrated by immunocytochemistry with an antiserum to molluscan cardioexcitatory peptide. AB - Neurosecretory cells were histochemically identified in the thoracic ganglia of the Colorado potato beetle and Drosophila melanogaster with an antiserum to the molluscan cardioexcitatory neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2). These cells and the FMRFamide-immunoreactive neurosecretory cells identified in a locust are most likely homologous. The neurosecretory axon terminals in the 3 species use different neurohaemal organs. Such a structural diversity in release sites of apparently homologous neurosecretory cells in different species may account for the large structural variability in neurohaemal organs in insects in general. PMID- 3104838 TI - Weighing the costs and the benefits of students education to service agencies. PMID- 3104839 TI - The enterococcus--bacterial pathogen of the 1990s. PMID- 3104840 TI - Further probes into the molecular sites of damage to cerebral adenylate cyclase following postischemic reperfusion. AB - A variety of pharmacological agents were used as experimental probes to determine with greater precision the site(s) of damage to cerebral adenylate cyclase as a consequence of postischemic reperfusion in the gerbil. A paradigm of 60-min bilateral ischemia followed by 40-min reperfusion results in a decreased sensitivity of the catalytic site of adenylate cyclase to Mn2+. Likewise, the GTP transducer site (guanine nucleotide regulatory or G protein) revealed depressed responses to GTP in the absence or presence of norepinephrine, dopamine agonists, substance P, yohimbine, and cholera and pertussis toxins. Moreover, a crude preparation of GTPase disclosed that damage elicited by postischemic reperfusion was directed to the higher-affinity form of this enzyme, which is associated with the overall function of the guanine nucleotide regulatory protein. Injury to adenylate cyclase was unrelated either to the ability of adrenergic ligands to bind to associated receptor sites or to the capacity of the brain to generate visual evoked potentials in response to visual stimuli. PMID- 3104841 TI - Preventing multiple body tube mix-ups. PMID- 3104842 TI - Legal implications of removal of feeding tubes. PMID- 3104843 TI - Case-mix: matching patient need with nursing resource. PMID- 3104844 TI - FY'88: RAPping the ball to the MDs. PMID- 3104845 TI - Pregnancy complications among diabetic women: review 1965-1985. PMID- 3104846 TI - With cost-effectiveness analysis firms can compare health programs. PMID- 3104847 TI - DRGs and quality care. PMID- 3104848 TI - Influence of chronic melatonin on 9,10-dimethyl-1,2-benzanthracene-induced mammary tumors in female Holtzman rats exposed to continuous light. AB - Daily treatment of 'functionally' and surgically pinealectomized female Holtzman rats reared in continuous light (light:dark schedule, 24L:OD) with oral melatonin (100 micrograms/day/rat) initiated 30 days prior to and 90 days following 9,10 dimethyl-1,2-benzanthracene (DMBA) administration on day 55 of age, resulted in a highly significant suppression of mammary tumor incidence and prolongation of latency period of tumor appearance (p less than 0.001). An identical treatment schedule of melatonin to intact rats given DMBA, housed in short photoperiods (10L:14D), also resulted in a significant suppression of tumor incidence (p less than 0.05), though the latency period of tumor appearance was not prolonged. These results demonstrate for the first time that replacement or additive manipulations of melatonin from puberty to adulthood plays a critical role in the suppression of DMBA-induced mammary tumors. PMID- 3104849 TI - The possibility of measuring blood flow in the optic nerve head in the live eye. PMID- 3104850 TI - Home transfusion therapy: a new dimension in home care. AB - Visiting Nurse Service, Inc (VNS), of Akron, Ohio, has provided transfusion therapy in the home since January 1984. Home transfusion has proved a valuable alternative to inpatient treatment and to expensive, exhausting ambulance trips to the hospital for outpatient treatment for selected homebound patients, many of whom are terminally ill. The VNS program is based on detailed policies and procedures that include patient referral criteria, RN education, patient education, blood procurement and labelling, and protocols for transfusion complications. Recognizing the need for patient safety, VNS has a quality assurance program that provides for continuous monitoring and evaluation of the home transfusion therapy, especially of any adverse reactions that occur. PMID- 3104851 TI - Voluntary accreditation, government regulation, and nursing home quality. PMID- 3104852 TI - The American Psychiatric Association's psychiatric case management program. PMID- 3104853 TI - Monitoring and evaluation of the quality and appropriateness of care: an ambulatory health care example. Staff of the Division of Education and the Division of Accreditation, Joint Commission on Accreditation of Hospitals. PMID- 3104854 TI - The use of billing data in quality assurance. PMID- 3104855 TI - Assessing the quality of care in a hospital emergency unit: a framework and its application. AB - This article presents a specific application of a general approach to quality assessment by describing in detail both the theoretical and the practical aspects of quality assessment in a hospital emergency unit. The theoretical framework is established by specifying the level and scope of assessment, adopting a definition of quality, modeling emergency care as a succession of phases, specifying evaluative attributes, choosing a method for case selection, and selecting one or more methods of assessment. The practical application of this framework is illustrated using two methods, "tracer" and "trajectory," and selecting specific conditions amenable to assessment with each method. PMID- 3104856 TI - Faculty practice in home health care: a new education and service relationship in process. PMID- 3104857 TI - Predeposit autologous blood transfusion: an analysis of donor attitudes and attributes. AB - Predeposit autologous blood transfusion now accounts for 11% of the total transfusion volume at Saint Cloud Hospital in Minnesota. This hospitalwide program represents a major positive quality assurance/risk management change in transfusion practice. To understand the factors responsible for the success of the program, a questionnaire was sent to 224 patients donating during a 26-month period ending July 1, 1985. Factors important in the increasing utilization of the program include donor acceptance, clinician referrals, and perceived lack of conflict with the homologous donation process. PMID- 3104859 TI - A simple approach to quality assurance in a complex ambulatory care setting. AB - In an effort to implement ongoing and continuous monitoring and evaluation of the quality of care in its unusually complex ambulatory care setting, the University of Chicago Hospitals developed a system of clinic-based activity. All 60 of its clinics use the same procedure, involving indicators that address both servicewide and clinic-specific concerns and a single, adaptable tool for data collection and reporting that makes it easier for centralized bodies to review and act on reports. Specific examples show how the system has improved care and encouraged multidisciplinary involvement in the quality assurance effort. PMID- 3104858 TI - The ambulatory care parameter: a structured approach to quality assurance in the ambulatory care setting. AB - Assessing the quality of ambulatory care is difficult because practitioners see patients for only a short time and because the goals of care are not always clearly defined. The ambulatory care department of Methodist Hospital of Indiana, Inc, has developed a system, called ambulatory care parameters, that helps ambulatory health care professionals sort through the complexities of ambulatory care. The ten parameters provide a framework for evaluating the care provided. PMID- 3104861 TI - Two examples of monitoring and evaluating quality and appropriateness of care: a residential treatment center and hospice. PMID- 3104860 TI - Contextual and organizational correlates of the quality of hospital nursing care. PMID- 3104862 TI - Von Recklinghausen's neurofibromatosis. AB - More is being learned each year about the manifestations of neurofibromatosis, but unfortunately no cure has been found. In otolaryngology we see patients with this disease presenting a wide variety of pathology, which can include any of the regions or organs of the head and neck. Table 1 summarizes the otolaryngic manifestation of von Recklinghausen's disease. A well thought out management plan usually requires some sort of surgical management, as well as close coordination with other medical and surgical specialists who are also treating the patient. Due to the multiple organ system involvement in neurofibromatosis, a team approach is the most beneficial for the patient's progress and assistance in leading as functionally and cosmetically normal a life as possible. PMID- 3104863 TI - Annual meeting of the American Academy of Otolaryngology--Head and Neck Surgery Foundation, Inc. San Antonio, Texas, September 14-18, 1986. Abstracts. PMID- 3104864 TI - Murine spleen and lymph node cellular composition and function during cyclophosphamide and splenectomy induced resistance to Toxoplasma gondii. AB - Murine toxoplasmosis caused by a low virulence, cyst-forming strain of Toxcoplasma gondii (Pe strain) is characterized by splenomegaly, lymphadenopathy, decreased delayed-type hypersensitivity (DTH), and the presence of toxoplasma cysts in brain tissue. Cyclophosphamide (CY) in a single dose of 100 mg/kg injected 3 days before infection, or splenectomy 3 weeks before infection, augmented DTH and decreased the number of toxoplasma brain cysts. CY-induced augmentation of resistance during the first 3 weeks of murine toxoplasmosis was associated with: (1) an increase in mononuclear phagocytes and a decrease in T lymphocytes (including Lyt2+ cells) in spleens and lymph nodes; (2) suppressed toxoplasma antigen induced proliferation of cultured spleen cells: (3) augmentation of antigen induced proliferation of cultured lymph node cells; and (4) low levels of interferon-gamma production in both spleen and lymph node cultures. The best correlate of the enhanced in-vivo effects of CY was proliferation of nylon wool-purified lymph node cells to toxoplasma antigen. The presence of Lyt2+ cells in lymph nodes of toxoplasma infected mice inhibited maximal proliferation. PMID- 3104865 TI - Effect of protective and non-protective antibodies in the phagocytosis rate of Trypanosoma cruzi blood forms by mouse peritoneal macrophages. AB - The phagocytosis of Trypanosoma cruzi blood forms by mouse peritoneal macrophages is significantly enhanced by sera from chronic chagasic patients, rabbits and mice presenting 'lytic antibodies' (LA) which are associated with resistance and active infections as well as 'conventional serology antibodies' (CSA) which are immunoglobulins involved in the positivity of serological diagnostic tests. The phagocytosis rate, however, is not influenced by sera from mice immunized with T. cruzi antigen or chagasic patients submitted to specific treatment, both displaying only CSA but not LA. The efficacy of LA in increasing phagocytosis is related to their ability to bind to epitopes of living trypomastigotes, a property lacking in CSA that bind only to fixed parasites. This phenomenon is apparently the reason for the low effectiveness of antigens used for vaccination in Chagas' disease which only induce CSA, immunoglobulins apparently unable to mediate a number of regular effector immune mechanisms such as complement mediated lysis, antibody-dependent cell cytotoxicity and phagocytosis. PMID- 3104866 TI - [Release of plasminogen activator by SIN-1]. AB - SIN-1--a pharmacologically active metabolite of the vasodilating agent molsidomine--caused an increase in plasminogen activator release of about 50 per cent at a final concentration of 10(-7) mol/l on perfusion of isolated pig ears. An increase in SIN-1 concentration did not produce a further increase in activator release. The released activator is of the tissue-type. After repeated perfusion of the isolated pig ear with SIN-1 no further significant increase in plasminogen activator release occurred. PMID- 3104867 TI - [Biological effects of SIN-1 in the vascular wall]. AB - The biological effects of two vasodilatory drugs, SIN-1 (the active metabolite of molsidomine) and nitroglycerin were analysed in the arterial endothelium and vascular muscle. Both drugs induce the secretion of prostacyclin in endothelial cells in culture, but this secretion is short-lived and occurs for high doses of the two drugs (above 10(-5)M). These same drugs induce a dose-dependent relaxing effect on the smooth muscle contracted either by norepinephrine or 5 hydroxytryptamine with an ED50 of 5.10(-7)M. This relaxation is neither secondary to an endothelium-derived product nor to a cyclooxygenase or lipoxygenase-derived product. PMID- 3104868 TI - [Influence of molsidomine, SIN-1 and nitroglycerin on the metabolism of prostaglandins by human fibroblasts]. AB - In human skin fibroblasts, exposed during 24 h to molsidomine and SIN-1, the functional status of prostaglandin synthesis is altered in so far, that the bradykinin stimulation of thromboxane is inhibited whereas the production of other PG's is not different from control. Exposure to GTN induces no such inhibition of thromboxane. During the first 5 minutes of exposure, both SIN-1 and GTN stimulate the synthesis of 6-oxo-PGF1-alpha and of PGE2 but not of TXB2. Whereas SIN-1 shows a cumulative stimulatory effect with bradykinin, GTN lacks this effect. According to the findings of this human cell model, we conclude that the sydnonimines, like GTN, stimulate, at least under the present conditions, the formation of vasodilatory prostaglandins and, in addition, that they inhibit irreversibly the formation of proaggregatory thromboxane. PMID- 3104869 TI - [Assessment of the gas-transport function of human erythrocytes in an isolated rat heart model]. PMID- 3104870 TI - [Growth of transplantable aflatoxin B1-induced mammary cancer in Wistar rats during treatment with BCG vaccine]. PMID- 3104871 TI - Limitations in the use of indium-111-oxine-labeled leucocytes for the diagnosis of occult infection in children. AB - Fifteen children underwent scintigraphy with indium 111 (111In)-labeled white blood cells (WBC) for the detection of a local suppuration. The procedure generally contributed to a correct diagnosis. False negative results were observed in 5 children, but in two of them positive foci were also present. The missed lesions were 2 liver abscesses, 1 lung abscess, foci of osteomyelitis and 1 pericarditis. Two cases of chronic granulomatous disease are presented in which increased leucocyte accumulation was not observed in proven instances of infection. PMID- 3104872 TI - A case of pericardial hemangioma with consumption coagulopathy cured by radiotherapy. AB - An infantile case of pericardial hemangioma with large pericardial effusion and consumption coagulopathy is described. This is the first reported case of pericardial hemangioma cured by radiotherapy. PMID- 3104873 TI - Validation of doubly labeled water for assessing energy expenditure in infants. AB - Previous studies show that the doubly labeled water method is accurate for measuring energy expenditure in the adult human. To validate this method in infants, carbon dioxide production rate and energy expenditure were measured for 5 to 6 days by doubly labeled water (DLW) and periodic open circuit respiratory gas exchange (RGE) in 10 blinded studies in nine infants following abdominal surgery. Infants were maintained on consistent oral or parenteral nutrition prior to and during study. This avoided diet-related changes in baseline isotopic enrichment of body water which could theoretically contribute to significant errors in calculation of carbon dioxide production rate. For DLW, insensible water loss was assumed to be proportional to respiratory volume and body surface area, where the former was predicted from carbon dioxide production rate. Insensible water loss thus calculated averaged 18% of water turnover. Rates of carbon dioxide production measured by DLW were not significantly different from that of RGE (10.4 +/- 1.1 and 10.5 +/- 0.9 l/kg/day, mean +/- SD, respectively). Energy expenditure was calculated using respiratory quotients from dietary intake (DLW:DIET) and RGE (DLW:RGE) data. There was no significant difference between energy expenditure determined by DLW (DLW:DIET and DLW:RGE) and that measured by RGE (58.5 +/- 6.1, 56.8 +/- 6.1, and 57.3 +/- 5.1 kcal/kg/day, mean +/- SD, respectively). Rate of carbon dioxide production, DLW:diet, and DLW:RGE calculated by DLW differed from corresponding RGE values by -0.9 +/- 6.2, -1.1 +/ 6.1, and 1.6 +/- 6.2%, mean +/- SD, respectively. These findings demonstrate the validity of the doubly labeled water method for determining energy expenditure in infants without concurrent water balance studies. PMID- 3104874 TI - Erythrocyte age-dependent changes of membrane protein 4.1: studies in transient erythroblastopenia. AB - In high resolution sodium dodecyl sulfate-gel electrophoresis, the red cell protein, band 4.1, separates into a and b forms, which are closely sequence related polypeptides. In membranes from patients with hemolytic anemia, the relative amount of band 4.1b is increased, which has led to a suggestion that the relative proportion of these two 4.1 forms might be age dependent (Sauberman N, Fortier NL, Fairbanks GF, O'Connor RJ, Snyder LM 1979 Biochim Biophys Acta 556:292-313). We have measured the relative proportions of bands 4.1a and b in the red cells of seven patients with transient erythroblastopenia of childhood. In this disease, temporary cessation of erythroid cell production occurs, and the circulating red cells represent an aged cohort of erythrocytes. At diagnosis, the band 4.1 of red cell membranes was nearly entirely in the a form, and as reticulocyte levels rose during recovery, the predominant form became 4.1b. After recovery, the a/b ratio returned to normal. A transient period of moderate reticulocytosis and high levels of 4.1a could be detected in some cases, presumably marking the beginning of the recovery phase. These results support the proposal that the 4.1 band ratio is an internal marker of cell age in the human erythrocyte. PMID- 3104875 TI - Risk factors associated with candidemia in the neonatal intensive care unit: a case-control study. AB - Systemic candidiasis, especially candidemia, is an increasing problem among high risk neonates. Although possible predisposing factors have been suggested, no case-control study has evaluated potential risk factors. By retrospective chart review we identified 21 infants admitted to the neonatal intensive care unit between 1976 and 1983 (0.9% of all admissions) who had documented nosocomial candidemia before 4 months of age. Twenty patients were matched to a control infant with similar birth weight and date of admission. We found that the median durations of exposure to the following risk factors were significantly longer in patients compared with controls: hyperalimentation; intravenous fat emulsion; endotracheal tubes; and/or tracheostomies and antibiotic therapy. However, by discriminant analysis, duration of antibiotic therapy remained the variable most strongly (and independently) associated with the development of candidemia. Treatment of the 22 episodes of candidemia was variable including catheter removal alone in 12 and a combination of catheter removal, amphotericin, 5 fluorocytosine and/or ketaconazole in the others. Although the overall mortality for the series was 5 of 20 cases (25%), no infant larger than 2000 g died. We conclude that development of candidemia in neonates is associated with, and possibly caused by, prolonged exposure to antibiotics (as documented by multivariate analysis), hyperalimentation, intravenous fat emulsion and tracheal intubation (as documented by univariate analysis). To the greatest extent possible consistent with good clinical care, exposure to these risk factors should be minimized in high risk neonates. PMID- 3104876 TI - Effects of carbon dioxide on preoptic thermosensitive neurons in vitro. AB - Effects of carbon dioxide (CO2) on the firing rates of preoptic thermosensitive neurons were examined in rat brain slice preparations. The perfusing medium was saturated with gas mixtures consisting of 90% O2 and one of various concentrations (5%, 6.3%, 7.5%, and 10%) of CO2 balanced with N2. The medium containing 5% CO2 was used as control. Most preoptic neurons were inhibited during application of a high CO2 medium. An excitatory effect of CO2 on a small number of neurons was also significant, although this was weak and transient compared to the inhibitory effect. Thermosensitivities of the neurons did not correlate with their CO2 sensitivities. The influence of CO2 tended to be more evident at higher temperatures. We conclude that the direct effect of CO2 on PO thermosensitive neurons as well as on thermally insensitive neurons is mainly inhibitory. PMID- 3104877 TI - [Lupus anticoagulant]. PMID- 3104879 TI - Human carbonic anhydrase I cDNA. PMID- 3104878 TI - Molecular characterization of bsg25D: a blastoderm-specific locus of Drosophila melanogaster. AB - The blastoderm stage of Drosophila embryogenesis is a time of crucial transitions in RNA transcription, the cell cycle and segment determination. We have previously identified three loci encoding RNAs specific to this stage (Roark et al., Dev. Biol. 109, 476-488, 1985). We present here the complete nucleotide sequence of one of these loci, bsg25D, which encodes a 2.7 kb blastoderm-specific RNA. The primary structure of this RNA, and that of an overlapping 4.5 kb RNA, has been determined. The amino acid sequence of the predicted bsg25D protein has been compared to the NBRF protein database. Structural similarities between domains in the bsg25D, fos, and tropomyosin proteins, and their possible significance for early embryogenesis are discussed. PMID- 3104880 TI - Nucleotide sequence of phycocyanin beta-subunit gene of cyanobacterium Anacystis nidulans strain R2. PMID- 3104881 TI - The human kappa deleting element and the mouse recombining segment share DNA sequence homology. AB - We have used cloned mouse and human DNA probes to identify regions of conserved homology between the human and murine DNA segments, (termed kappa deleting element (kde) and recombining segment (RS) respectively) which are frequently recombined in lambda-producing B cells. Heteroduplex analysis indicated extensive homology in the region immediately downstream of the recombination site of both segments. This was confirmed by Southern and direct nucleotide sequence analyses. Fifty percent homology was detected within the 500 nucleotides that neighbour the recombination points in the kde and RS segments. These results indicate that the kde and RS sequences are evolutionarily conserved and may be functionally relevant to normal B cell development. PMID- 3104882 TI - Complete variable region sequence of a nonfunctionally rearranged kappa light chain transcribed in the nonsecretor P3-X63-Ag8.653 myeloma cell line. PMID- 3104884 TI - Sequence of the adenine methylase gene of the Streptococcus faecalis plasmid pAM beta 1. PMID- 3104883 TI - Translational regulation of the L11 ribosomal protein operon of Escherichia coli: mutations that define the target site for repression by L1. AB - The L11 ribosomal protein operon of Escherichia coli contains the genes for L11 and L1 and is feedback regulated by the translational repressor L1. The mRNA target site for this repression is located close to the Shine-Dalgarno sequence for the first cistron, rp1K (L11). By use of a random mutagenesis procedure we have isolated and characterized a series of point mutations in the L11 leader mRNA which eliminate or greatly diminish the regulation by L1. The mutations define a region essential for translational regulation upstream of the L11 Shine Dalgarno sequence and identify a region of structural homology with the L1 binding site on 23S rRNA. These results are also consistent with the previously proposed model for the secondary structure of the L11 leader mRNA. PMID- 3104885 TI - Activation of c-Ha-ras proto-oncogene by in vitro chemical modification with 2 amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 4-nitroquinoline N oxide (4NQO). AB - Chemical modification of a plasmid containing the human c-Ha-ras proto-oncogene (pSVMBras-gpt) in vitro with the ultimate carcinogens N-acetoxy-2-amino-6 methyldipyrido[1,2-a: 3',2'-d]imidazole (N-OAc-Glu-P-1) and N-acetoxy-4 aminoquinoline N-oxide (N-OAc-4AQO) generated an activated oncogene that transformed NIH3T3 cells. As DNA is only cellular macromolecule present in the reactions, the results clearly show that the chemical modification of DNA with carcinogens alone can cause the induction of transformation of mammalian cells. PMID- 3104886 TI - Effects of modification of 4-thiouridine in E. coli tRNAfMet on methylation reaction with a thermostable Gm-methylase. AB - Gm-methylase isolated from an extreme thermophile, Thermus thermophilus HB 27 methylates the 2'-OH of the ribose of G18 in the consensus GG sequence in the D loop, by recognizing the D loop-and-stem structure as a minimal substrate. Modification of s4U8 of E. coli tRNAfMet with S-benzylthioisothiourea resulted in a considerable decrease in methylation activity of Gm-methylase. The effect was cancelled by reduction with beta-mercaptoethanol. However, aminoacylation activity and methylation activity of m1A-methylase were scarcely influenced by the modification. These results suggest the involvement of s4U8 residue of tRNA in the recognition of Gm-methylase. PMID- 3104887 TI - Effects of onion extract on the development of hamster buccal pouch carcinomas as expressed in tumor burden. AB - One-hundred male, young-adult Syrian hamsters (Mesocricetus auratus) were divided into five equal groups of 20 animals each. Groups 1, 2, and 3 were painted three times a week in the left buccal pouches with a 0.5% solution of 7,12 dimethylbenz[a]anthracene (DMBA) in mineral oil. Group 1 animals also received a 20% onion extract in their drinking water and were also painted in left buccal pouches three times a week with a 50% onion extract in mineral oil. Group 2 animals received the onion extract in their drinking water, but they received only mineral oil in buccal pouches as a control for the painting with onion extract in mineral oil. Group 3 animals received DMBA but no onion extract. Group 4 animals received onion extract but no DMBA, and Group 5 animals were left untreated. Onion extract was found to significantly delay tumor formation in Groups 1 and 2 compared with Group 3 DMBA controls. PMID- 3104888 TI - Hydrazine sulfate: a current perspective. AB - Hydrazine sulfate is an anticachexia agent which interrupts host energy wasting as a result of the malignant process. An inhibitor of gluconeogenesis at the phosphoenolpyruvate carboxykinase (PEP CK) reaction, this agent has been shown in randomized, placebo-controlled, double-blind trials to improve glucose tolerance, reduce glucose turnover, increase caloric intake, and increase or stabilize weight; in single-arm controlled trials, this agent has been shown to increase appetite, improve performance status, decrease pain, diminish anorexia, normalize laboratory indices, stabilize tumor growth, induce tumor regression, and promote survival, while inducing little to no important clinical side effects. In view of its demonstrated capacity to effect anticancer response, this drug is suggested for trial as a sole agent in early drug-resistant cancer, in combination with cytotoxic and related therapies, and in conjunction with total parenteral nutrition. It is postulated that effective control of the mechanisms associated associated with cancer cachexia may contribute to control of malignant disease. PMID- 3104889 TI - The effect of different levels of dietary beta-carotene on DMBA-induced salivary gland tumors. AB - Different levels of beta-carotene (0, 5, 25, 125, and 250 mg/kg diet) were tested for their chemoprevention effects using 9,10-dimethyl-1,2-benzanthracene-induced salivary gland tumor model in rats. Tumor incidence and tumor weights were slightly lower in rats fed diets supplemented with 25 mg or more beta-carotene/kg diet. Hepatic vitamin A and beta-carotene levels were increased in a dose dependent fashion, reaching a plateau at 125 mg beta-carotene/kg diet. In plasma, beta-carotene concentrations were also increased with an increase in dietary beta carotene. Vitamin A levels in plasma were not affected. The normal salivary glands had higher concentrations of beta-carotene than did the tumors. The results suggest that the decreases in tumor incidence and tumor weight may be related to the increase in plasma and tissue levels of beta-carotene as a result of feeding high levels of beta-carotene. PMID- 3104890 TI - Protective effect of CR 1409 (cholecystokinin antagonist) on experimental pancreatitis in rats and mice. AB - CR 1409, a glutaramic acid derivative with competitive cholecystokinin antagonistic activity, was administered IP and evaluated in comparison with proglumide (the model CCK-receptor antagonist), gabexate (protease inhibitor) and PGE2 (cytoprotective) on two different models of experimental pancreatitis. Acute pancreatitis was induced in mice by six IP injections of 50 micrograms/kg caerulein at hourly intervals. The drugs were administered 30 minutes before each caerulein administration. Blood samples and pancreata were collected 3 hours after the last caerulein injection. In the second experiment, pancreatitis was induced in rats by injecting 0.3 ml 6% sodium taurocholate interstitially into the pancreas. The drugs were administered twice, 30 minutes before and 3 hours after taurocholate. The animals were killed 6 hours after laparotomy and blood samples and pancreata were collected. CR 1409 exhibited on both pancreatitis models a protective effect in a dose range of 0.3-10 mg/kg. Proglumide exhibited a protective activity at higher doses (200-400 mg/kg). Gabexate and PGE2 were effective only in pancreatitis induced by taurocholate in a dose range of 30-60 mg/kg and 60-130 micrograms/kg respectively. These results, showing a high protective effect of CR 1409 on different models of acute pancreatitis, suggest an important role of CCK in the pathogenesis of pancreatitis. PMID- 3104891 TI - [Tube feeding. Indications, methods and practical aspects]. PMID- 3104892 TI - Characterization of different amyloids with immunological techniques. AB - We studied 71 cases of amyloidosis from the autopsy material of our institute. 17 cases were secondary amyloidosis of which 7 had initially been diagnosed as primary amyloidosis; all cases reacted positively with an anti-substance A antibody; 13 showed a suppression and 4 a strong reduction of the Congo red staining following tissue incubation in KMnO4. 25 cases were identified as primary amyloidosis of which 7 had initially not been recognized as such. In 16 cases amyloid deposits reacted positively with antibodies specific for the light chains of the immunoglobulins (3 X kappa, 13 X lambda). A monoclonal plasmacytic cell proliferation in the bone marrow was seen in 14 cases. In all cases deposits were KMnO4 resistant, but 1 case showed a slight reduction of staining intensity. 27 cases were cardio-vascular (senile) amyloidosis; in 20 cases at least 3 organs showed deposits; 12 cases had deposits in 5 and more organs. 2 cases were heredofamilial amyloidosis. In those 29 cases deposits reacted positively with an anti-prealbumin antibody, but were negative for AA and the light chains of the immunoglobulins; the Congo red staining remained strong in all cases when previously incubated in KMnO4. KMnO4-Congo red staining and antisera specific for AA, L-chains and prealbumin proved of value for classification of amyloidosis and for its organ distribution. PMID- 3104893 TI - The direct lateral approach to the hip for arthroplasty. Advantages and complications. AB - The direct lateral approach to the hip as described by Hardinge in 1982 was used in the performance of 83 hip arthroplasties. This approach was found to give excellent visualization of the proximal femur and acetabulum and was found to have comparable operative time, blood loss, time to ambulation, and range of motion to other approaches. The postoperative dislocation rate was very low (2.5%) and redislocations have not occurred. The incidence of heterotopic ossification was high (61%) and this may limit the use of this approach in some cases. PMID- 3104894 TI - [Role of arachidonic acid metabolites in the mediation of pain]. PMID- 3104895 TI - [The structure of the infectious scrapie agent]. PMID- 3104896 TI - Chelation in metal intoxication. XXIV: Influence of various components of vitamin B complex on the therapeutic efficacy of disodium calcium versenate in lead intoxication. AB - The supplementation of vitamin-B complex reduces lead intoxication. With a view to identify the components of vitamin-B complex responsible for such protection, riboflavin, calcium pentothenate, pyridoxine, nicotinamide, folic acid and cyanocobalamine were investigated for their ability, and their influence on the efficacy of disodium calcium versenate (Na2CaEDTA), to enhance the urinary excretion of lead, mobilize tissue lead and restore lead induced biological alterations in lead intoxicated rats. Folic acid and pyridoxine besides thiamine may be the responsible factors in prophylaxis of lead poisoning by vitamin B complex or in enhancing the antidotal properties of Na2CaEDTA. PMID- 3104897 TI - [Treatment of pulmonary tuberculosis patients with primary drug resistant Mycobacterium tuberculosis]. PMID- 3104898 TI - [Differentiation of M. tuberculosis and M. bovis using the salicylate test and nitrate reduction]. PMID- 3104899 TI - B lymphocyte-specific protein binding near an immunoglobulin kappa-chain gene J segment. AB - Nuclear extracts from pre-B and B cell lines contain a nuclear DNA binding protein (kappa locus protein, KLP) that specifically recognizes a DNA sequence in the immunoglobulin kappa light chain joining (J) segment gene region. KLP is not observed in mature B cells, T cells, or nonlymphoid cell types. Two tandem binding sites for KLP designated KI and KII have been identified by methylation interference analysis to be immediately proximal to the J kappa 1 nonamer heptamer recognition sequences and separated by 38 base pairs from each other. Fragments of DNA containing KI and KII sites compete for binding to KLP, and both protein-DNA complexes have the same electrophoretic mobility. Other flanking sequences of immunoglobulin gene fragments do not bind to KLP. The position of KLP-DNA binding and its tissue-specific expression suggest that it may be involved in the regulation of lymphoid gene DNA rearrangements by targeting recombinase to the kappa-chain gene region. PMID- 3104900 TI - Peptide and nucleotide sequences of rat CD4 (W3/25) antigen: evidence for derivation from a structure with four immunoglobulin-related domains. AB - The rat W3/25 antigen was the first marker antigen of helper T lymphocytes to be identified. Subsequently, the human OKT4 antigen (now called CD4) was described, and cell distribution and functional data suggested that W3/25 and OKT4 antigens were homologous. This is now confirmed by the matching of peptide sequences from W3/25 antigen with sequence predicted from rat cDNA clones detected by cross hybridization with a cDNA probe for human CD4. Analysis of the two sequences suggests an evolutionary origin from a structure with four immunoglobulin-related domains, although only domain 1 at the NH2 terminus meets the standard criteria for an immunoglobulin-related sequence. CD4 domains 2 and 4 contain disulfide bonds but seem like truncated immunoglobulin domains, whereas domain 3 may have a pattern of beta-strands like an immunoglobulin variable domain, but without the disulfide bond. PMID- 3104901 TI - Genes for the major protein antigens of Mycobacterium tuberculosis: the etiologic agents of tuberculosis and leprosy share an immunodominant antigen. AB - Mycobacterium tuberculosis genes encoding immunologically relevant proteins were isolated by systematically screening a lambda gt11 recombinant DNA expression library with a collection of murine monoclonal antibodies directed against protein antigens of this pathogen. These antibodies, previously characterized by a World Health Organization workshop on monoclonal antibodies against mycobacteria, were used to isolate DNA sequences encoding five major protein antigens of this pathogen. To evaluate the extent of crossreactivity between these M. tuberculosis antigens and antigens of Mycobacterium leprae, recombinant antigens were probed with monoclonal antibodies directed against the protein antigens of these bacilli. One of the antigens, a 65-kDa protein, has determinants common to M. tuberculosis and M. leprae. We find not only that this antigen is recognized by mouse monoclonal antibodies but that it is the major protein recognized by anti-M. tuberculosis rabbit sera. The 65-kDa proteins of M. tuberculosis and M. leprae appear to play a role in the humoral and cell-mediated immune response to these pathogens. PMID- 3104902 TI - Induction of aldose reductase and sorbitol in renal inner medullary cells by elevated extracellular NaCl. AB - Aldose reductase [aldehyde reductase 2; alditol:NAD(P)+ 1-oxidoreductase, EC 1.1.1.21] catalyzes conversion of glucose to sorbitol. Although its activity is implicated in the progression of ocular and neurological complications of diabetes, the normal function of the enzyme in most cells is unknown. Both aldose reductase activity and substantial levels of sorbitol were previously reported in renal inner medullary cells. In this tissue, the extracellular NaCl concentration normally is high and varies considerably depending on the urine concentration. We report here on a line of renal medullary cells in which medium that is high in NaCl greatly increases both aldose reductase activity and intracellular sorbitol. In these tissue culture cells (and presumably also in the renal inner medulla), the intracellular sorbitol helps balance the osmotic pressure of elevated extracellular NaCl and thus prevents cellular dehydration. PMID- 3104903 TI - Oxygen transfer involving nonheme iron: the influence of leaving group ability on the rate constant for oxygen transfer to (EDTA)Fe(III) from peroxycarboxylic acids and hydroperoxides. AB - Ethylenediaminetetraacetato iron(III) [(EDTA)Fe(III)] has been shown to react with a series of four peroxycarboxylic acids and four alkyl hydroperoxides (YOOH; dry methanol solvent, 30 degrees C) by heterolytic O-O bond scission that accompanies the transfer of an oxygen atom to the iron(III) moiety [(EDTA)Fe(III) + YOOH----[(EDTA)(FeO)]+ + YOH]. A single linear free-energy relationship exists for both peroxycarboxylic acids and alkyl hydroperoxides when the logarithm of the second-order rate constant (kYOOH) for reaction of YOOH species with (EDTA)Fe(III) is plotted vs. the pKa of the YOH leaving group. PMID- 3104904 TI - Sporulation-specific sigma factor sigma 29 of Bacillus subtilis is synthesized from a precursor protein, P31. AB - Evidence is presented that a sporulation-essential sigma factor of Bacillus subtilis, sigma 29, is synthesized as an inactive precursor (P31) and that its activation occurs by a developmentally regulated cleavage of 29 amino acids from the P31 amino terminus. A pulse-chase experiment demonstrated that sigma 29 was derived from a preexisting protein, with appearance of radioactively labeled sigma 29 paralleling the disappearance of labeled P31. The disappearance of pulse labeled P31 did not occur when the experiment was done with a B. subtilis strain carrying a mutation in a locus (spoIIE) required for sigma 29, but not P31, synthesis. Microsequencing of sigma 29 protein revealed that its amino terminus originates at amino acid 30 of the P31 amino acid sequence. In order to test whether a proteolytic event alone could activate P31 to a protein with sigma 29 like properties, a fusion protein (P31*) containing most of P31 was overproduced in Escherichia coli and converted in vitro into a protein with the electrophoretic mobility of sigma 29 by limited treatment with Staphylococcus aureus V8 protease. Protease-treated P31*, but not untreated P31*, was capable of directing B. subtilis core RNA polymerase to specifically initiate RNA synthesis at a sigma 29-recognized promoter in vitro. PMID- 3104906 TI - Evolution of accelerated senescence in laboratory populations of Drosophila. AB - Ecological theories of life history evolution predict that natural selection should favor semelparous life histories in environments where juvenile survival is high relative to adult survival and rates of population growth are high. That is, organisms should complete their entire reproductive effort in a short period of time following maturation. Direct empirical verification of this idea has been lacking. Six independent populations of Drosophila melanogaster were maintained in two different environments, called r and K, for more than 120 generations. In the r environment population size was small, larval survival and rates of population growth were high, and reproduction was limited to a few days after eclosion. In the K environment population size was large and larval survival low, but adults were allowed to reproduce indefinitely. The fecundity of females of different sizes from each environment was measured daily for 4 weeks. No differences in fecundity were seen during the first week of adult life for females from the two environments. By the fourth week, however, the fecundity of large females from the r environment was 47-83% less than that of females from the K environment. The accelerated senescence exhibited by females from the r environment appears to be due to the accumulation of deleterious alleles whose effects are expressed late in life, which is consistent with the mutation accumulation hypothesis for the evolution of senescence. PMID- 3104905 TI - GTP-binding domain: three consensus sequence elements with distinct spacing. AB - A sequence comparison of nine functionally different GTP-binding protein families has yielded further information on the general characterization of the conservation and importance of amino acid sequences in the GTP-binding domain, including a consensus sequence composed of three consensus elements GXXXXGK, DXXG, and NKXD with consensus spacings of either 40-80 or approximately equal to 130-170 amino acid residues between the first and second elements and approximately 40-80 amino acid residues between the second and third sequence elements; the sequence NKXW in place of NKXD in the sequence element responsible for base specificity allows the use of ITP as well as GTP; dGTP can be used with essentially the same efficiency as GTP; signal transducing proteins and enzymes have been identified in the nine families; and family conservations allow the identification of the most probable consensus sequence element when more than one is present. Employing these features we have screened the protein sequence data base of the Protein Identification Resource and have identified only known GTP binding proteins with the exception of protein 2C from foot-and-mouth disease virus as matching the consensus sequence. Based on this finding we predict that foot-and-mouth disease virus protein 2C binds GTP and, by analogy, that protein 2C from several related viruses (polio, rhino, encephalomyocarditis, and cowpea mosaic) will bind a nucleotide as part of its biologic activity. PMID- 3104907 TI - Progressive dysplasia and aneuploidy are hallmarks of mouse skin papillomas: relevance to malignancy. AB - We report a systematic histopathologic study of papillomas at different times during promotion, correlating the results with those from cytogenetic analysis of the same tumors. Papillomas were induced in SENCAR mice by two-stage carcinogenesis (7,12-dimethylbenz[a]anthracene and phorbol 12-myristate 13 acetate). Individual tumors were randomly sampled at different times during promotion, and histopathologic and cytogenetic studies were carried out on every tumor. Early during promotion (10 weeks), most papillomas were well differentiated hyperplastic lesions with mild or no cellular atypia. No tumors showed severe dysplastic changes. By 20 weeks of promotion, a dramatic drop had occurred in the number of lesions with no dysplasia. Most of the tumors presented moderate dysplasia, and some already showed severe dysplastic changes. At later stages (30-40 weeks), most of the papillomas were classified as moderately or severely dysplastic papillomas, and several were considered to be intrapapillomatous carcinomas. This histopathologic evaluation was supported by nuclear measurements performed on papillomas at different time points. Chromosomal abnormalities followed a similar trend. Papillomas seem to start as diploid lesions, but between 10 and 20 weeks of promotion, hyperdiploid cells can be observed in almost every tumor. In some cases the stem line was taken over by aneuploid clones. At 40 weeks of promotion, all papillomas were aneuploid, most of them with hyperdiploid stem lines. A positive correlation was found between the histological and cytogenetic studies, with the most aggressive and atypical tumors being the more aneuploid. These results support the idea that most, if not all, papillomas are truly premalignant lesions in different stages of the potential progression toward malignancy. Chromosomal abnormalities might play an important role in the sequence of events leading to malignancy. PMID- 3104908 TI - Synthetic peptide with inhibin-like activity preferentially inhibits follitropin secretion in comparison with lutropin-releasing hormone antagonists. AB - Biological activity of a synthetic peptide with inhibin-like activity under in vitro and in vivo conditions was compared with three highly potent synthetic lutropin-releasing hormone antagonists. Unlike the synthetic lutropin-releasing hormone antagonists, which effectively inhibited both lutropin and follitropin secretion from the pituitary, the inhibin-like peptide showed a preferential effect by inhibiting follitropin release both in vitro and in vivo. Thus, small peptides such as inhibin-like peptide with a sequence unrelated to lutropin releasing hormone may provide a basis for design of selective inhibitors of gonadotropin release. PMID- 3104909 TI - High-affinity interleukin 2 binding by an oncogenic hybrid interleukin 2 epidermal growth factor receptor molecule. AB - Both interleukin 2 (IL-2) and epidermal growth factor (EGF) receptors exist in two forms that differ with respect to affinity for their ligand. Only the high affinity receptors appear to be responsible for the proliferation signal delivered upon binding of the growth factor. Fibroblasts transfected with IL-2 receptor cDNA generate only low-affinity receptors for IL-2, but fusion of membranes from these fibroblasts with T-cell membranes converts some receptors to high affinity, indicating the involvement of a T cell-specific factor in the generation of high-affinity receptors. We have constructed a chimeric cDNA molecule containing the extracellular IL-2-binding domain of the IL-2 receptor cDNA and the transmembrane and intracellular tyrosine kinase domains of the EGF receptor cDNA. When transfected into fibroblasts, this IL-2-EGF receptor cDNA generated high-affinity receptors for IL-2. Moreover, fibroblasts transfected with the chimeric molecule were morphologically transformed and produced rapidly growing tumors in nude mice. PMID- 3104910 TI - Functional analysis of a palindromic sequence required for normal replication of several staphylococcal plasmids. AB - Most small multicopy antibiotic-resistance plasmids of Staphylococcus aureus contain a major axis of hyphenated dyad symmetry (palA) that is required for normal replication and stability, although located outside of the minimal replicon. Rearrangements affecting palA cause plasmid instability, a marked reduction in copy number, and the accumulation of large quantities of strand specific circular single-stranded plasmid DNA. In view of the recent observation that pT181 initiates replication by a nick and 3'-extension mechanism (S. Khan, personal communication), it is suggested that these plasmids replicate by an asymmetric rolling-circle mechanism in which the displaced plus strand remains single stranded until palA is exposed, forming a hairpin that serves as the lagging strand origin. PMID- 3104911 TI - Mutations in the 2-microns circle site-specific recombinase that abolish recombination without affecting substrate recognition. AB - The site-specific recombinase encoded by the yeast plasmid 2-microns circle (FLP) forms a transient covalent linkage with its substrate DNA via a tyrosine residue, which appears to be located near its COOH terminus. The homology of the COOH terminus of FLP with that of the Int family of recombinases suggests that tyrosine-343 of FLP could be involved in forming the DNA-protein bridge. We have mutated tyrosine-343 to a phenylalanine or serine. We demonstrate that the binding of each of the two mutant proteins to its substrate is indistinguishable from that of wild-type FLP. However, both mutant proteins are incapable of catalyzing strand cleavage and recombination. PMID- 3104912 TI - Interferons regulate the in vitro differentiation of multilineage lympho-myeloid stem cells in hairy cell leukemia. AB - In vitro 14-day cultures of peripheral blood mononuclear cells from hairy cell leukemia patients consistently showed the presence of hematopoietic stem cells giving rise to multilineage colonies containing a high proportion of lymphoid cells associated with the myeloid and erythroid progenitors. These stem cells are not the hairy cells but appear to be pluripotent lymphomyeloid primitive stem cells persisting in this leukemia. Interferon alpha c or beta 1 did not inhibit the growth of these colonies, as they did the growth of colonies of normal hematopoietic progenitors, but markedly decreased the ratio of lymphoid to myelomonocytic cells, by increasing the formation of monocytes and other nonlymphoid cell types in these multilineage colonies. Interferon gamma did not have the same effects on differentiation. PMID- 3104913 TI - Incomplete Y chromosomes promote magnification in male and female Drosophila. AB - We have recently shown that magnification, an increase in the number of ribosomal RNA genes (rDNA) in gametes produced by rDNA-deficient flies, can occur in female Drosophila if they have a Y chromosome. We now have tested several X-Y translocation and recombinant chromosomes to determine which parts of the Y chromosome are necessary for magnification to occur in females. Our data indicate that the required region is the distal part of the long arm of the Y chromosome, YL. We have also used X-Y translocation chromosomes to study magnification of rDNA-deficient X chromosomes in males. Our data show that the region of the Y chromosome from the distal end of the nucleolus organizer through the centromere is not required for magnification in males. The frequency of magnification in males with rDNA-deficient Y fragments is comparable to that produced by Ybb-, a chromosome that has often been used to produce magnification in males. These results demonstrate that the Ybb-chromosome is not uniquely effective in causing magnification to occur in males. The results of these studies imply that sequences present on YL are required for magnification to occur in females; these sequences are probably also required for magnification in males. Since unequal sister chromatid exchange has been implicated as the major mechanism of ribosomal gene increase during magnification, the YL sequences required for magnification may be involved in encoding or regulating products needed for sister chromatid recombination in germ-line cells. PMID- 3104914 TI - Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners. AB - To elucidate the mechanism of the t(14;18)(q32;q21) chromosomal translocation found in follicular lymphoma, we examined the structure of both derivative (der) chromosomal breakpoints as well as their germ-line predecessors. We noted that chromosome segment 18q21 was juxtaposed with immunoglobulin heavy (H) chain gene diversity (DH) regions on all five der(18) chromosomes we examined, and we confirmed the juncture with immunoglobulin H-chain gene joining (JH) regions on the der(14) chromosome. However, the t(14;18) was not fully reciprocal in that chromosome 14 DNA between the DH and JH regions was deleted. Furthermore, extra nucleotides, reminiscent of "N" segments, were present at the der(14) and possibly der(18) junctions. This indicates that despite the mature B-cell phenotype of follicular lymphoma, the t(14;18) occurs during attempted DH-JH joining, the earliest event in immunoglobulin rearrangement in a pre-B-cell. Our detailed analysis of the germ-line 18q21 region indicated that most breakpoints clustered within a 150-base-pair major breakpoint region. However, we found no evidence for evolutionarily conserved immunoglobulin-like recombinational signals at 18q21, arguing against a role for immunoglobulin recombinase in chromosome 18 breakage. Instead, a direct repeat duplication of chromosome 18 sequences was discovered at both chromosomal junctures, typical of the repair of a naturally occurring staggered double-stranded DNA break. These results prompt a translocation model with illegitimate pairing of a staggered double-stranded DNA break at 18q21 and an immunoglobulin endonuclease-mediated break at 14q32 and with N-segment addition, repair, and ligation to generate der(14) and der(18) chromosomes. PMID- 3104916 TI - Pseudomonas exotoxin coupled to a monoclonal antibody against ovarian cancer inhibits the growth of human ovarian cancer cells in a mouse model. AB - In an effort to devise an alternative treatment for human ovarian cancer, we have isolated a monoclonal antibody (OVB-3) that reacts with all ovarian cancers tested (10/10) but few normal tissues. An immunotoxin produced by coupling OVB-3 to Pseudomonas exotoxin kills ovarian cancer cells in tissue culture and prolongs the life of animals bearing human ovarian cancers. These data suggest that this immunotoxin should be evaluated as a treatment for ovarian cancer in women. PMID- 3104917 TI - Scrapie, an unconventional virus: the current views. PMID- 3104915 TI - Adult B-cell repertoire is biased toward two heavy-chain variable-region genes that rearrange frequently in fetal pre-B cells. AB - Fetal pre-B cells rearrange a very restricted set of immunoglobulin variable genes for the heavy chain (VH). To determine whether the adult B-cell repertoire is similarly skewed, we first identified the genes that rearrange in pre-B cells from BALB/c mice and then determined their frequency of rearrangement in adult B cells. In fetal pre-B cell lines, two genes, VH81X from the 7183 subfamily and VHOx2 from the Q52 subfamily, comprise 75% of the rearranged alleles of an estimated 1000 genes (P less than 0.001). Sequencing analyses revealed that rearrangements involving the two genes were both productive and nonproductive. The biased rearrangement of these two VH genes persists in B-cell hybridomas from adult mice at a frequency of 22%, as determined by Southern gel analysis and RNA sequencing. The sequence of one VHOx2 rearrangement from a hybridoma shows that the rearrangement is productive, suggesting that the gene encodes an antibody that could participate in the immune response. The data indicate that the adult B cell repertoire is not random concerning usage of individual VH genes, and it may be shaped by the unknown mechanisms that cause preferential rearrangement of certain genes early in ontogeny. PMID- 3104918 TI - Aspirin-induced gastric injury in the rat: histologic changes and sucralfate cytoprotection. AB - The effect of pretreatment with intragastric sucralfate on aspirin acid-induced gastric mucosal lesions in the rat was studied. The finding by others that sucralfate is cytoprotective and that this cytoprotective effect probably is mediated, at least in part, by stimulation of endogenous prostaglandin synthesis was confirmed. In addition, a time course study revealed that the maximum cytoprotective effect was present 1 min after sucralfate administration and persisted for at least 6 hr. Microscopic evaluation of histologic sections revealed that sucralfate significantly decreased aspirin-induced deep mucosal erosions (those extending into the parietal cell area) but not superficial mucosal damage. Superficial mucosal damage (surface cell injury and erosions involving the mucous neck cell area) could not be detected grossly. The lesions seen grossly were deeper erosions involving the parietal cell area of the mucosa. PMID- 3104919 TI - Growth hormone response of bull calves to growth hormone-releasing factor. AB - Three experiments were conducted to determine serum growth hormone (GH) response of bull calves (N = 4; 83 kg body wt) to iv injections and infusions of human pancreatic GH-releasing factor 1-40-OH (hpGRF). Peak GH responses to 0, 2.5, 10, and 40 micrograms hpGRF/100 kg body wt were 7 +/- 3, 8 +/- 3, 18 +/- 7, and 107 +/- 55 (mean peak height +/- SEM) ng/ml serum, respectively. Only the response to the 40-microgram dose was greater (P less than 0.05) than the 0-microgram dose. Concentrations of prolactin in serum were not affected by hpGRF treatment. In calves injected with hpGRF (20 micrograms/100 kg body wt) at 6-hr intervals for 48 hr, GH increased from a mean preinjection value of 3.1 ng/ml serum to a mean peak response value of 70 ng/ml serum. Differences in peak GH response between times of injection existed within individual calves (e.g., 10.5 ng/ml vs 184.5 ng/ml serum). Concentrations of GH in calves infused continuously with either 0 or 200 micrograms hpGRF/hr for 6 hr averaged 7.4 +/- 3 and 36.5 +/- 11 ng/ml serum, respectively (P less than 0.05). Concentrations of GH oscillated markedly in hpGRF-infused calves, but oscillations were asynchronous among calves. We conclude that GH response of bull calves to hpGRF is dose dependent and that repeated injections or continuous infusions of hpGRF elicit GH release, although magnitude of response varies considerably. We hypothesize that differences in GH response to hpGRF within and among calves, and pulsatile secretion in the face of hpGRF infusion may be related to the degree of synchrony among exogenous hpGRF and endogenous GRF and somatostatin. PMID- 3104920 TI - [How to be a social force]. PMID- 3104921 TI - [Historical profile of the National Nursing Association. I]. PMID- 3104922 TI - [Study of the labor market and of the professional introduction of licensed nurses from 1978 to 1984]. PMID- 3104924 TI - [Nursing diagnosis. Its foundations reside in a conceptual model]. PMID- 3104925 TI - [Nursing diagnosis. A pedagogical application]. PMID- 3104923 TI - [Facts on acquired immunodeficiency syndrome (AIDS)]. PMID- 3104927 TI - ["Computers and nursing". Computerized nursing kardex]. PMID- 3104926 TI - [Nursing diagnosis. The why of its importance]. PMID- 3104928 TI - [Apropos of the selection for admission to nursing schools]. PMID- 3104929 TI - [Standards of nursing care]. PMID- 3104930 TI - [International Council of Nurses. Directives for the development of research on nursing care]. PMID- 3104931 TI - Effects of 5-bromo-2'-deoxyuridine on arachidonic acid metabolism of neuroblastoma and leukemia cells in culture: a possible role of endogenous prostaglandins in tumor cell proliferation and differentiation. AB - Effects of 5-bromo-2'-deoxyuridine (BrdU) were studied on two neuroblastoma and two leukemia cell lines, in terms of the relationship between prostaglandin (PG) synthesis and cell growth/differentiation. After treatment with BrdU (5 micrograms/ml), cell growth of the 4 cell lines was inhibited and one neuroblastoma cell line (GOTO) showed flattened morphology with positive S-100 protein, one of the differentiation markers for Schwann or glial cells. In the 4 cell lines, BrdU treatment reduced [1-(14)C]-arachidonic acid incorporation into phosphatidylinositol and phosphatidylethanolamine and was associated with an increase into phosphatidylcholine and triglyceride. BrdU treatment also increased fractions of 6-keto-PGF1 alpha and PGF2 alpha, with a decreased TXB2 fraction. The decreased ratio of TXB2/6-keto-PGF1 alpha or increased 6-keto-PGF1 alpha fraction correlated significantly with cell growth inhibition, suggesting that the changes in the balance of endogenous PGs might be associated with BrdU induced cell growth inhibition with or without differentiation of neuro-blastoma and leukemia cells in culture. PMID- 3104932 TI - Effects of scopolamine on locomotor activity and metabolic rate in mice. AB - Reduction of metabolic rate occurs in rodents in response to intoxication with several chemicals, including amphetamine. In the present study, cholinergic mediation of locomotor activity and metabolic rate was investigated by measuring the effects of scopolamine on the frequency of photobeam breaks, the rate of CO2 production, and rectal temperature in unrestrained mice. Increasing doses of scopolamine (0, 0.3, 1.0, 3.0, and 10.0 mg/kg IP) increased locomotor activity over a 72-min observation period. CO2 production (as minute volume exhaled CO2, VECO2), measured simultaneously with locomotor activity, was suppressed equally at all doses of the drug. Rectal temperatures taken 72 min after scopolamine declined slightly in a dose-related manner. These results parallel earlier findings with d-amphetamine and suggest that divergent effects on metabolic rate and locomotor activity may be induced by centrally-acting compounds acting on more than one neurochemical system. PMID- 3104933 TI - Suppressive effects of intraventricular injected dopamine and nomifensine on muricide induced by thiamine deficiency. AB - The effects of dopamine (DA) and nomifensine (NF) on muricide activity induced by thiamine deficiency were examined. The chronic administration of L-dopa and nomifensine during feeding of thiamine deficient diet attenuated the muricide activity. Moreover, acute administration of L-dopa or nomifensine (IP) and dopamine or nomifensine (ICV) suppressed the thiamine deficiency-induced muricide activity dose-dependently. Small doses of apomorphine inhibited the muricide response significantly. The suppressive effects of dopamine and nomifensine were antagonized by pretreatment with 6-hydroxydopamine, but were not changed by pretreatment with p-chlorophenylalanine. These results suggest that the dopaminergic system has an important role in the regulation to the thiamine deficiency-induced muricide response. PMID- 3104934 TI - Investigation of dressings designed for treatment of alveolitis sicca dolorosa ("dry socket"). Part 3: Influence of mannitol and sorbitol on properties of tablets and dressings comprising acetylsalicylic acid, mefenamic acid and aseptin P. AB - In the dressings for dry tooth sockets, mannitol and sorbitol as solid hydrophilizers have been applied. Increase of concentrations of these hydrophilizers in the tablets results in dressings with increased swelling ability and pharmaceutical availability but decreased viscosity and resistance to washing out. These properties of the dressings are also influenced by medicinal substances present. The dressing fills the tooth socket within several min, removes pain and remain there for 24-48 h. PMID- 3104935 TI - [The effect of ambroxol and bromhexine on the "respiratory burst" of alveolar macrophages]. AB - The effect of ambroxol and bromhexine on the yeast cell wall- and arachidonic acid (AA)-induced luminol-respectively lucigenin-dependent chemiluminescence (CL) of alveolar macrophages (AM) of patients with lung diseases has been investigated. Both drugs cause a suppression of the induced CL. These results suggest that ambroxol and bromhexine reduce the generation of reactive oxygen metabolites (ROM) by AM. The mechanism of action is thought to involve the activation of the acyl-CoA: lysophosphatide acyltransferase. The increase of this enzyme activity lowers probably the intracellular concentration of free AA and consequently also the production of ROM. The investigations show a new possibility for the influence of biosynthesis of ROM and likely of eicosanoids, which play an important role as pathogenetic mediators in different lung diseases. PMID- 3104936 TI - The effect of surface finish on the reflection of CO2 laser beams from specula. AB - A potential source of hazard during gynaecological surgery with a CO2 laser is the reflection of the laser beam from the surfaces of the metal speculum. An experimental method of measuring the levels of radiation reflected from a variety of surfaces is described. Results which compare the effectiveness of different surface treatments in reducing reflections and show how this varies over a range of angles of incidence are presented. The significance of the results in terms of hazards to patients and staff is discussed. PMID- 3104938 TI - Photoinitiated DNA damage by melanogenic intermediates in vitro. PMID- 3104937 TI - Photochemistry of melanin precursors: dopa, 5-S-cysteinyldopa and 2,5-S,S' dicysteinyldopa. PMID- 3104939 TI - Regulated synthesis of phycobilisome components. PMID- 3104940 TI - Time resolved quenching study of serine-195 labeled alpha-chymotrypsin. PMID- 3104941 TI - Spectral dependence of some UV-B and UV-C responses of Tetrahymena pyriformis irradiated with dye laser generated UV. PMID- 3104942 TI - Characteristics of vestibular reactions to canal and otolith stimulation at an early stage of exposure to microgravity. PMID- 3104943 TI - [Long-term rehabilitation of chronic alcoholic patients at psychiatric halfway houses]. AB - The psychiatric adjustment centre is an important link in the treatment of chronic alcoholics. The adjustment centre attached to the County. Neurological Hospital at Lubben is used as an example to discuss the problems associated with sheltered work, living and recreation places. On the basis of four years of experience it can be said that some 10% of our patients with alcohol problems, most of whom have already broken links with their families and some of whom have already rejected society, require this form of treatment. Attention is drawn to the gradual transition from ward to outpatient treatment of patients with alcohol problems. PMID- 3104944 TI - Grades 1 and 2 hypothyroidism in a state mental hospital: risk factors and clinical findings. AB - Thirty-six chronically psychotic patients (nine men and 27 women, mean age 56.7 +/- S.D. 13.4 years) were found to have elevated thyroid stimulating hormone (TSH) levels during review of thyroid function screening tests of 1150 patients over a 15 month period in a 700 bed state mental hospital. This study population of 36 patients was more likely to be female and older than the general hospital population. The spectrum and frequency of psychiatric diagnoses included dementia (3); schizoaffective disorder (12); bipolar disorder (6); schizophrenic disorder (4); organic affective disorder (7); major depression (3); and mental retardation (1). Only nine of these 36 patients failed to receive the goitrogens lithium (LI), carbamazepine (CBZ) and/or phenytoin (PTN) and five of those nine patients had a history of thyroid disease. Sex did not predict age, thyroxine (T4) level, triiodothyronine (T3) uptake, or TSH. The distribution of psychiatric diagnoses were the same for both sexes. Expectedly, there was an inverse relationship between TSH and T4 and T3 uptake. Using T4 to separate grades 1 and 2 hypothyroidism revealed that six (17%) patients had grade 1 disease. Men were more likely to have a seizure disorder and receive LI, CBZ, and PTN. Women were more likely to have a history of thyroid disease. The goitrogenic effects of LI + CBZ seemed additive compared with patients receiving LI alone. While T4, T3 uptake, and LI levels were the same for the two groups, patients receiving LI + CBZ had higher TSH values (p = 0.028) than did patients receiving LI alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3104945 TI - MMPI indicators of long-term therapy in a college counseling center. PMID- 3104946 TI - Hypothalamic control of pituitary and adrenal hormones during hypothermia. AB - In order to investigate neuroendocrinological mechanisms of hypothermia, we determined the changes in plasma concentrations of corticosterone (CS), prolactin (PRL), and thyrotropin (TSH), and their correlations with alterations in hypothalamic dopamine (DA) and thyrotropin releasing hormone (TRH), in rats restrained and immersed in a water bath at various temperatures. A graded decrease of body temperature induced a progressive increase in the plasma level of CS, whereas that of PRL showed a drastic decrease. The plasma level of TSH also showed an increase during mild hypothermia (about 35 degrees C), but this increase was not evident during profound hypothermia (below 24 degrees C). The changes in these hormones were readily reversed by rewarming animals. Although DA content in the hypothalamus was not affected, its metabolites, 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), showed an increase following the decrease of body temperature. Pretreatment of the animals with sulpiride, a D2-antagonist, prevented the hypothermia-induced inhibition of PRL release. Hypothalamic TRH was significantly decreased during mild hypothermia, and it returned to control levels after rewarming. These results suggest that the decrease in plasma PRL induced by hypothermia may be associated with the activation of hypothalamic DA neurons, whereas the increase in plasma TSH during mild hypothermia seems to be caused by the increased release of TRH in the hypothalamus. PMID- 3104947 TI - Influence of free thyroid hormone levels on the TSH response to TRH in endogenous depression. AB - The TSH response to TRH (delta max TSH) and the serum concentrations of free thyroxine (FT4), 3,5,3'-, and 3,3',5'-triiodothyronine (FT3 and FrT3) were studied in two groups of patients with endogenous depression before and after clinical recovery following electroconvulsive treatment (ECT). Before ECT, the patients from group 1 (n = 17) had a reduced delta max TSH (p less than 0.01), which after ECT rose to values not different from those found in controls. FT4 levels were elevated before ECT (p less than 0.01), and they decreased after ECT (p less than 0.05) to levels similar to those found in controls. FT3 and FrT3 levels were not different from the control values, but FrT3 decreased during ECT (p less than 0.01). In group 2 (n = 19), delta max TSH was reduced both before (p less than 0.02) and after (p less than 0.01) ECT. FT4 levels were increased both before and after ECT (p less than 0.02). Both parameters were unaffected by ECT. The data are compatible with the assumption that the decreased TSH response to TRH found in patients with endogenous depression is secondary to an increase in circulating FT4. PMID- 3104948 TI - Intoxicating effects of lorazepam and barbital in rat lines selected for differential sensitivity to ethanol. AB - The motor impairing effects and plasma concentrations of barbital and lorazepam were studied in the alcohol tolerant (AT) and alcohol non-tolerant (ANT) rat lines developed for low and high sensitivity to motor impairment from ethanol. The mixed (M) line, from which the AT and ANT rats were derived, was also included in the study. Like ethanol, barbital and lorazepam impaired the performance of the ANT rats more than that of the AT rats. The motor performance of the M rats was relatively more impaired after barbital than after lorazepam administration at the same dose used in the AT and ANT rats. At the two latter time points (2.5 and 3.5 h) the sensitive ANT rats had significantly higher serum barbital concentrations than the AT rats. The serum barbital concentrations of the AT and ANT rats did not differ, however, at the two first time points (0.5 and 1.5 h) of the tilting plane tests, although the ANT rats were significantly more intoxicated. The concentrations of lorazepam in plasma do not explain the differential motor impairment either, since the sensitive ANT rats had lower plasma concentrations than the insensitive AT rats. The results, thus, suggest that the selection involved in the development of the AT and ANT lines has not been specific for ethanol. The results also support the idea that ethanol, barbiturates and benzodiazepines have some modes of action in common. PMID- 3104949 TI - A comparative assay of nefopam, morphine and d-amphetamine. AB - Nefopam is a non-opioid analgesic reported to have some stimulant properties. The subjective, behavioral and physiological effects of nefopam, morphine and d amphetamine were compared in seven non-dependent substance abusers to assess the abuse potential of nefopam. Morphine and d-amphetamine had significant effects on a number of measures generally consistent with the effects of drugs of the opioid and psychomotor stimulant drug classes. Subjects correctly discriminated between morphine and d-amphetamine. Nefopam was most frequently identified by subjects as being amphetamine-like, though several measures indicated that nefopam produced some sedation. Little or no "liking" of the effects of nefopam was reported by subjects. Overall, nefopam was one fifth as potent as morphine and one quarter as potent as d-amphetamine in producing subjective and physiological effects. The results indicate that nefopam is neither entirely morphine-like nor d-amphetamine like. In our opinion, nefopam has a lesser potential to be abused than morphine or d-amphetamine. PMID- 3104950 TI - Suppression of deprivation-induced water intake in the rat by opioid antagonists: central sites of action. AB - The effects of naltrexone methobromide, a quaternary derivative of the opioid antagonist naltrexone, were investigated on deprivation (24 h)-induced water intake in the unilaterally cannulated rats. Naltrexone methobromide reduced post deprivational water intake with an ED50 of 7.3 micrograms when tested at 30 min (peak effect) after intracerebroventricular administration. It also dose dependently (0.3-10 micrograms) depressed water intake, with peak effects at 15 min, after microinjection into the paraventricular hypothalamic nucleus and into the supraoptic hypothalamic nucleus. The drug did not produce any other effects on behaviors. The ED50S were 1.4 micrograms when given into the paraventricular nucleus, and 3.3 micrograms when given into the supraoptic nucleus, respectively. Although injections of higher doses (1.0, 3.0 and/or 10 micrograms) of the drug into the preoptic area, zona incerta, and corpus callosum significantly suppressed water intake, other behavioral manifestations, such as rotational behaviors, convulsions, body shakes, head swaying, and/or backward locomotion were manifested simultaneously with the reduction in drinking. When injected into the lateral hypothalamic area, water intake was not significantly affected by the drug. These findings suggest that the paraventricular and supraoptic hypothalamic nuclei are important sites of action in the naltrexone-induced suppression of water intake. PMID- 3104951 TI - Fluoxetine suppresses palatability-induced ingestion. AB - Non-deprived rats were allowed 1-h access to a range of saccharin solutions from 0.001 to 0.1 M Na saccharin. Compared to a group of rats drinking tap water, the rats drinking the saccharin solutions ingested a great deal more fluid, with as much as 24-30 ml consumed of the 0.01 M concentration, compared to 3-5 ml in controls. Fluoxetine (IP) decreased this palatability-induced excessive consumption in a dose-related manner. Effects of 10 mg/kg fluoxetine were apparent for 48 h after injection. This effect on palatability-induced ingestion may relate to previously reported effects of fluoxetine on food consumption. PMID- 3104953 TI - Behavioral sensitization to methamphetamine in the rat: an ontogenic study. AB - The behavioral effect of repeated methamphetamine (MAP) treatment was observed in young rat to establish the ontogenetic period crucial to methamphetamine sensitization. Animals were treated with MAP (2 mg/kg, SC) once daily for 5 days (Group 1: postnatal days 2-6, G-2: 7-11, G-3: 12-16, G-4: 17-21, G-5: 22-26, G-6: 27-31). Control animals were similarly treated with an equal volume of saline. On the 35th postnatal day, all rats were challenged with MAP (2 mg/kg, IP). Behavioral sensitization to MAP was not found in G-1, G-2, G-3 or G-4, although responsiveness to MAP was observed in rats after the 2nd postnatal day. The animals in G-5 and G-6 showed hypersensitivity to MAP in locomotor activity and stereotyped behavior. These findings indicate that the period crucial to behavioral sensitization to MAP corresponds to the period of presynaptic dopamine autoreceptor formation in the rat brain. PMID- 3104952 TI - Benzodiazepine ligands, nociception and 'defeat' analgesia in male mice. AB - Recent studies have indicated that defeat experience induces acute non-opioid analgesia in intruder mice. To investigate the potential involvement of benzodiazepine receptors in this biologically-relevant form of environmentally induced antinociception, we initially assessed the effects of some benzodiazepine ligands on basal nociception (tail-flick assay). Chlordiazepoxide (5-30 mg/kg), midazolam (0.625-5 mg/kg), diazepam (0.5-4 mg/kg), Ro15-1788 (5-80 mg/kg) and CGS8216 (5 mg/kg) were found to be ineffective in altering basal nociception. However, higher doses of CGS8216 (10-20 mg/kg) induced significant analgesia, an effect also observed with the beta-carboline derivatives FG7142 (5-20 mg/kg) and DMCM (1-2 mg/kg). Time-course analyses revealed that the onset of CGS8216 analgesia was slower than for FG7142 and DMCM, but that all three drugs produced long-lasting elevations in tail-flick latencies. The analgesic effects of FG7142 and DMCM were completely reversed by Ro15-1788 (20 mg/kg) and by chlordiazepoxide (20 mg/kg), suggesting mediation by benzodiazepine receptor mechanisms. Although CGS8216 analgesia was also reversed by Ro15-1788, it was unaffected by chlordiazepoxide; however, diazepam (5 mg/kg) did significantly attenuate the reaction. Further studies indicated that the antinociceptive consequences of defeat experience were dose-dependently blocked by Ro15-1788 (10-40 mg/kg) and by diazepam (0.5-2 mg/kg). Surprisingly, however, neither chlordiazepoxide (5-20 mg/kg) nor midazolam (1.25-2.5 mg/kg) blocked "defeat" analgesia under present test conditions. Although several issues remain unresolved, present findings would not be inconsistent with the proposal that stimuli associated with the acute stress of defeat experience release an endogenous ligand which acts in an "inverse agonist-like" manner at benzodiazepine sites. PMID- 3104954 TI - Enhancement by secoverine and physostigmine of retention of passive avoidance response in mice. AB - A one-trial passive avoidance test in the mouse, in which drugs were injected intraperitoneally immediately after the shocked acquisition trial, was used. The effects of enhancing central cholinergic transmission on retention of passive avoidance was investigated using secoverine, which blocks muscarinic autoreceptor mediated inhibition of acetylcholine release, and using physostigmine, an acetylcholinesterase inhibitor. Secoverine (1.0-5.0 mg/kg) and physostigmine (0.1 0.4 mg/kg) were found to improve retention of the avoidance response measured 24 h after acquisition. These effects were augmented when the two drugs were given in combination. In contrast, atropine (5.0 mg/kg) tended to impair retention of passive avoidance and blocked the facilitatory effects of physostigmine. The results support the hypothesis of a novel approach to treatment of memory disorders based on blockade of muscarinic autoreceptors, to augment central cholinergic activity. PMID- 3104956 TI - Increased growth hormone response to clonidine in 6-hydroxydopamine-treated rats. AB - Alpha 2-adrenergic receptors mediate adrenergic stimulation of growth hormone (GH) secretion in the rat. The GH response to the alpha 2-adrenergic agonist clonidine has thus been used as an index of alpha 2-adrenergic receptor responsiveness. Pharmacologic manipulations known to upregulate alpha 2 adrenergic receptor sensitivity would then be expected to result in an enhancement of the GH response to clonidine. To test this hypothesis, rats were injected in the lateral ventricle with either 6-hydroxydopamine or sterile saline. One month following the lesion, urethane-anesthetized rats from each group were administered clonidine or saline. Venous samples for plasma GH were drawn prior to or following the clonidine or saline administration. Rats administered clonidine had greater GH responses than those administered saline within either the lesioned or nonlesioned groups. The GH response to clonidine was significantly greater in the lesioned group than in the nonlesioned group. As 6-hydroxydopamine pretreatment upregulates alpha 2-adrenergic receptors, these results support the validity of the use of the GH response to clinidine as an index of alpha 2-adrenergic receptor responsiveness. PMID- 3104955 TI - Psychopharmacological investigations of a lead-induced long-term cognitive deficit in monkeys. AB - This study investigated pharmacological manipulations of the cholinergic (ACh) and dopaminergic (DA) transmitter systems in monkeys with a long-term lead induced cognitive deficit on delayed spatial alternation (DSA). Both ACh and DA have been found to be affected by developmental lead exposure and to be involved with performance on spatial learning and memory tasks. The lead-induced deficit in performance accuracy on DSA persisted throughout the 2 years of this experiment, which ended more than 8 years after the end of the postnatal lead exposure. Acute administration of agonists and antagonists of the ACh and DA systems did not elicit differential effects from the lead-exposed and control groups in terms of DSA per cent correct performance. The ACh antagonist, scopolamine, caused a dose-related decline in performance in both groups. Significant amelioration of the lead-induced DSA deficit was achieved by chronic treatment with the DA agonist, L-dopa. After withdrawal from L-dopa, the lead related deficit reappeared. Improvement in performance of the lead-treated group was also seen after chronic amphetamine administration, but this effect was not significant. These data implicate DA mechanisms in the long-lasting cognitive effects of developmental lead exposure. The alleviation of the deficit with chronic administration of a DA precursor points to a possible line of treatment for the cognitive effects of developmental lead exposure. PMID- 3104957 TI - Latent inhibition is not affected by acute or chronic administration of 6 mg/kg dl-amphetamine. AB - Latent inhibition (LI) is a behavioral paradigm in which animals learn to ignore a repeatedly presented stimulus not followed by meaningful consequences. We previously reported that LI was disrupted following the administration of 1.5 mg/kg dl-amphetamine. The present experiments investigated the effects of 6 mg/kg dl-amphetamine administration on LI in a conditioned emotional response (CER) procedure consisting of three stages: pre-exposure, in which the to-be conditioned stimulus, tone, was repeatedly presented without reinforcement; conditioning, in which the pre-exposed stimulus was paired with shock; and test, where LI was indexed by animals' suppression of licking during tone presentation. The three stages were conducted 24 h apart. In Experiment 1, the drug was administered in a 2 X 2 design, i.e. drug-no drug in pre-exposure and drug-no drug in conditioning. LI was obtained in all conditions. In Experiment 2, animals were given either 5 days of 6 mg/kg amphetamine pretreatment and amphetamine in pre-exposure and conditioning or 7 days of saline. LI was not obtained under amphetamine, but this outcome reflected a state-dependency effect. In Experiment 3, animals received either 5 days of amphetamine pretreatment and amphetamine in pre-exposure, conditioning and test or 8 days of saline. LI was obtained in both the placebo and amphetamine conditions. Experiments 4a and 4b compared the effects of two drug doses, 1.5 (4a) and 6 mg/kg (4b), administered in pre exposure and conditioning. LI was abolished with the 1.5 mg/kg dose but not with the 6 mg/kg dose. PMID- 3104958 TI - Enhanced muscimol-induced behavioral responses after 6-OHDA lesions: relevance to susceptibility for self-mutilation behavior in neonatally lesioned rats. AB - Adult rats lesioned with 6-hydroxydopamine (6-OHDA), either as neonates or as adults, demonstrated increased turning, compared to unlesioned controls, when muscimol was unilaterally microinjected into the substantia nigra reticulata (SNR). At the higher doses of muscimol, the lesioned rats were so intensely lateralized that circling was impeded. These data suggest a functional supersensitivity of receptors associated with GABA function in the SNR of 6-OHDA lesioned rats. When 30 ng muscimol was administered bilaterally into the SNR, self-mutilation behavior (SMB) was observed in 2/11 of the control unlesioned rats, in 0/8 adult 6-OHDA-lesioned rats, and in 11/11 of the neonatally-lesioned rats tested. The ability of muscimol to produce SMB in the rats lesioned as neonates was dose related. Behavioral observations indicated that behaviors associated with SMB (self-biting and taffy pulling) were present in neonatal, but not adult lesioned rats. Behavioral responses to dopamine agonist administration were also different between rats lesioned as neonates and those lesioned as adults with 6-OHDA. These data support the view that lesions of dopaminergic neurons cause an increased functional responsiveness of receptors acted upon by muscimol in the SNR, and that the increased susceptibility for SMB in neonatally lesioned rats is determined by neurons distal to the GABA receptor complex in the SNR. PMID- 3104959 TI - Modulation of social memory in male rats by neurohypophyseal peptides. AB - Adult male rats spend a great amount of time investigating novel juveniles. In contrast, rats re-exposed to the same juvenile 30 min after the initial exposure display little investigatory behavior. If the re-exposure occurs 2 h later, the juvenile is thoroughly investigated. These results have been interpreted to mean that rats form a transient memory for a particular juvenile. In the present study, memory was enhanced when the initial exposure to the juvenile was followed by another exposure to the same juvenile (retroactive facilitation) and impaired when exposure to the original juvenile was followed by exposure to another juvenile (retroactive interference). Arginine vasopressin had retroactive facilitating effects on social memory and these effects were blocked by the vasopressor antagonist dPTyr(Me)AVP. Moreover, the antagonist had retroactive interfering effects, since it impaired the recognition of a familiar juvenile. Oxytocin shared the same inhibitory pattern of action. These results suggest that neurohypophyseal peptides may have a prepotent role in modulating the mnemonic processing of chemosensory information associated with social interactions. PMID- 3104960 TI - Effect of diazepam on the speed of mental rotation. AB - The effect of diazepam on spatial visualization was studied using a double-blind crossover design. Diazepam 10 mg (or placebo) was given orally to 12 healthy young men at bedtime, followed again by 10 mg (or placebo) the next morning. One hour after the administration of the morning dose, the subjects performed a mental rotation task. Diazepam effects were analyzed in terms of an information processing model previously constructed to account for performance of the task. Using this method, the slope and intercept parameters of a linear function relating reaction time to task condition (i.e., angular difference in orientation between two identical stimulus figures) were computed for diazepam and placebo conditions. Diazepam significantly increased the slope and intercept of the mental rotation function (P less than 0.05). These results suggest that diazepam impairs spatial visualization ability. PMID- 3104961 TI - Food deprivation and stimulant self-administration in rats: differences between cocaine and d-amphetamine. AB - The effects of food deprivation (24 h) on response rates of rats self administering d-amphetamine and cocaine were compared. Food deprivation clearly increased rates of responding for both drugs but did so to a significantly greater extent for cocaine than for d-amphetamine. Consistent with other findings, the results suggest that the neural substrates underlying cocaine and d amphetamine reinforcement are not identical. PMID- 3104962 TI - Conditioned locomotion and place preference elicited by tactile cues paired exclusively with morphine in an open field. AB - A novel version of the conditioned place preference (CPP) technique was used in an attempt to determine whether tactile stimuli previously associated with morphine elicit approach and sustained contact. Empirical support for this view has been equivocal, prompting some to question the validity of the CPP technique. In the present study, rats received, during conditioning, morphine (10 mg/kg, IP) paired exclusively with an open field floor made of four quadrants of one texture (CS+) and saline with another floor made of four quadrants of a different texture (CS-). On the test for CPP, rats were given saline and placed in an open field containing either 1, 2, or 4 quadrants of the CS+ (with 3, 2, 0 quadrants of the CS-, respectively). These animals showed high absolute CPP scores on the test, spending, on average, as much as 83% and 75% of their time on the CS+ when two and one CS+ quadrants, respectively, were present. Concurrent measures of activity indicated that animals were most active when all four quadrants were CS+ and least active when zero or one CS+ quadrant was present. Thus, once an animal approached and made contact with the CS+ it tended to maintain contact with this stimulus and to reduce its approach to and contact with other stimuli. The differentiating features of this version of the CPP technique, as well as the relationship between morphine-induced conditioned locomotion and CPP, are discussed. PMID- 3104963 TI - The effect of the tricyclic antidepressant drug, nortriptyline on left ventricular ejection fraction and left ventricular volumes. AB - Eight patients with major depression but otherwise healthy underwent radionuclide cardiography before and during nortriptyline treatment. The second examination was performed when the nortriptyline plasma concentration was within the therapeutic range (60-150 micrograms X l-1). Heart rate, arterial blood pressure, left ventricular ejection fraction, left ventricular volumes, systolic pressure volume ratio, and cardiac output were determined. Heart rate increased in mean by 13% (P less than 0.05). All other variables were unchanged. We conclude that nortriptyline in therapeutic doses produces no major adverse effect on left ventricular function. Routine radionuclide cardiography might be a suitable method to detect among those treated with tricyclic antidepressants the occasional susceptible patient. This may particularly apply to patients with known heart disease and to elderly patients. PMID- 3104965 TI - [Pseudo-arguments for an economic benefit. Do psychotherapists really help control costs?]. PMID- 3104964 TI - Mecamylamine pretreatment increases subsequent nicotine self-administration as indicated by changes in plasma nicotine level. AB - Acute administration of mecamylamine, a centrally active nicotinic cholinergic agonist, has been shown to increase amount of smoking as indicated by smoking topography (e.g., puff rate, puff duration), expired carbon monoxide changes, and other inferential measures. In the present study, subjects showed significantly greater increases in plasma nicotine following smoking of two high-nicotine research cigarettes when pretreated with mecamylamine than when pretreated with placebo, even though no significant differences in puff volume or puff number were detected. Interestingly, none of our subjects reported nausea, although some achieved plasma nicotine levels at which nausea would typically be expected. We attribute the observed increases in nicotine intake to compensatory behavior designed to overcome mecamylamine's blocking effects. PMID- 3104966 TI - Seeking answers to the slowing progress in lowering infant mortality. PMID- 3104967 TI - ADAMHA goes into high gear in the prevention, research, and treatment of drug and alcohol abuse. PMID- 3104968 TI - A second opinion on Zuni diabetes. PMID- 3104969 TI - Overview of the National Infant Mortality Surveillance (NIMS) project--design, methods, results. AB - The recent slowdown in the decline of infant mortality in the United States and the continued high risk of death among black infants (twice that of white infants) prompted a consortium of Public Health Service agencies to collaborate with all States in the development of a national data base from linked birth and infant death certificates. This National Infant Mortality Surveillance (NIMS) project for the 1980 U.S. birth cohort provides neonatal, postneonatal, and infant mortality risks for blacks, whites, and all races in 12 categories of birth weights. (Note: Neonatal mortality risk = number of deaths to infants less than 28 days of life per 1,000 live births; postneonatal mortality risk = number of deaths to infants 28 days to less than 1 year of life per 1,000 neonatal survivors; and infant mortality risk = number of deaths to infants less than 1 year of life per 1,000 live births.) Separate tabulations were requested for infants born in single and multiple deliveries. For single-delivery births, tabulations included birth weight, age at death, race of infant, and each of these characteristics: infant's live-birth order, sex, gestation, type of delivery, and cause of death; and mother's age, education, prenatal care history, and number of prior fetal losses at 20 weeks' or more gestation. An estimated 95 percent of eligible deaths were included in the NIMS tabulations. The analyses focus on three components of infant mortality: birth weight distribution of live births, neonatal mortality, and postneonatal mortality. The most important predictor for infant survival was birth weight, with an exponential improvement in survival by increasing birth weight to its optimum level. The nearly twofold higher risk of infant mortality among blacks was related to a higher prevalence of low birth weights and to higher mortality risks in the neonatal period for infants weighing 3,000 grams or more, and in the postneonatal period for all infants, regardless of birth weight. Regardless of other infant or maternal risk factors, the black-white gap persisted for infants weighing 2,500 grams or more. PMID- 3104970 TI - Regional differences in birth weight-specific infant mortality, United States, 1980. AB - To describe regional differences in birth weight-specific infant mortality in the United States, we used data from the National Infant Mortality Surveillance project. The infant mortality risk (IMR) for the nation was 11.0 deaths per 1,000 live births. The risk (with 95 percent confidence intervals [CI]) for the four U.S. Census regions were West 9.9 (9.7 to 10.1), Northeast 10.4 (10.1 to 10.6), North Central 10.8 (10.6 to 11.0), and South 12.1 (11.9 to 12.3). In all regions, the IMR for blacks was approximately twice that of whites. Seventy-two percent of the higher IMR in the South was due to a higher proportion of black births compared with the remainder of the nation, reflecting the higher mortality rates suffered by black infants, and 28 percent to higher mortality among southern whites. The IMR for whites in the South was significantly higher than in the remainder of the nation: 9.8 versus 9.1 (relative risk = 1.09, CI = 1.06 to 1.11). Thirty-six percent of this excess in IMR was due to a higher frequency of low birth weight (less than 2,500 grams), 18 percent was due to higher IMR in infants with birth weight less than 2,500 grams, and 46 percent due to higher IMR in infants with birth weights of 2,500 g or more. Black infants born in the West had a lower risk of death than black infants in the other regions. When compared with the Northeast and South, 36 percent of the lower risk in the West among black infants was due to a lower frequency of low birth weight, 38 percent due to lower IMR in infants w'ith birth weight less than 2,500 g, and 26 percent to lower IMR in infants with birth weight of 2,500 g or more. PMID- 3104971 TI - Variation in state-specific infant mortality risks. AB - Data from the National Infant Mortality Surveillance project were used to examine the State-specific variations in infant, neonatal, and postneonatal mortality and to examine some of the factors affecting the risks of death. The infant mortality risk, defined as the risk of death before 1 year of age to an infant born in the 1980 birth cohort, in the highest risk State was nearly three times that in the lowest risk State. Mortality risk ratios of two or greater were found when comparing high and low States for overall black infant mortality risks, overall neonatal mortality, neonatal mortality risks for black and white infants examined separately, neonatal mortality risks for low birth weight infants regardless of race, and overall postneonatal mortality and postneonatal mortality for white infants. The lowest State-specific black mortality risks were higher than the highest white risks for overall infant mortality and neonatal mortality. The differences between State extremes in mortality risks are greater than the differences between the United States and the Scandinavian countries with the lowest infant mortality. PMID- 3104972 TI - Birth weight-specific infant mortality, United States, 1960 and 1980. AB - National statistics on the risk of infant mortality by birth weight were collected most recently in 1980 and 1960. (Infant mortality risk is the number of deaths of infants under 1 year of age per 1,000 live births.) In this 20-year period, the infant mortality risk (IMR) for single-delivery infants declined 53 percent, from 23.3 deaths per 1,000 live births to 11.0; 91 percent of this decline was due to lower IMRs within birth weight categories, and 9 percent was due to reduced frequency of low birth weight. The greatest reduction in neonatal mortality (under 28 days)--73 percent--occurred among infants of 1,500-1,999 grams (g) birth weight, whereas the greatest reductions in postneonatal mortality (28 days to under 1 year)--51 percent to 54 percent--occurred among infants of 3,500 g or more birth weight. Trends in IMR for black and white infants were similar, and the twofold gap between the races in IMR persisted from 1960 to 1980. For whites, reductions in the frequency of low birth weights contributed to the decline in the IMR. For blacks, the percentage of infants with birth weights of less than 1,500 g increased, and the total reduction in the IMR was attributable to lower birth weight-specific mortality risks. In some regions of the United States, failure to observe an increase in birth weight for blacks may be a reporting artifact, reflecting improved reporting of births of very small black infants in 1980. Examination of changes in perinatal mortality risks (from 20 weeks gestation to less than 28 days of life) did not suggest that infant mortality trends were substantially affected by changes in the distinction between fetal and neonatal deaths over the 20-year period. Reducing the number of low birth weight infants remains the greatest potential for future reductions in infant mortality. PMID- 3104973 TI - Birth weight-specific causes of infant mortality, United States, 1980. AB - To describe underlying causes of infant death by birth weight, we used data from the 1980 National Infant Mortality Surveillance project and aggregated International Classification of Diseases codes into seven categories: perinatal conditions, infections, congenital anomalies, injuries, sudden infant death syndrome (SIDS), other known causes, and nonspecific or unknown causes. Compared with heavier infants, infants with birth weights of 500-2,499 grams (g) are at increased risk of both neonatal and postneonatal death for virtually all causes. Sixty-two percent of neonatal deaths (under 28 days of life) were attributed to "conditions arising in the perinatal period," as defined using codes from the International Classification of Diseases. Prematurity-low birth weight and respiratory distress syndrome (RDS) were the leading causes of such deaths among infants with birth weights of 500-2,499 g, while birth trauma-hypoxia-asphyxia and other perinatal respiratory conditions were the leading causes among heavier infants. For all birth weight groups, congenital anomalies were the second leading cause, representing 27 percent of neonatal deaths. Although perinatal conditions caused nearly one-third of postneonatal deaths (28 days to under 1 year of life) among infants with birth weights of 500-1,499 g, for the other birth weight groups these conditions were much less important; predominant causes of postneonatal death were sudden infant death syndrome (SIDS), congenital anomalies, infections, and injuries. Black infants had a roughly twofold higher risk of neonatal and postneonatal death than did white infants for all causes except congenital anomalies, which occurred with almost equal frequency in blacks and whites. However, for infants with birth weights of 500-2,499 g, blacks had lower risks of neonatal death from RDS and congenital anomalies. Between 1960 (the latest year for which national birth weight-specific mortality statistics had been available) and 1980, SIDS emerged as a major diagnostic rubric. Otherwise, except for infections and congenital anomalies among infants with birth weights of 500-1,499 g, all causes of death declined in frequency among all birth weight groups. PMID- 3104974 TI - Birth weight-specific infant mortality due to congenital anomalies, 1960 and 1980. AB - The impact of mortality due to congenital anomalies in single-delivery births was compared in 1960 and 1980 birth cohorts; data were used from the 1960 National Center for Health Statistics national linkage of birth and death certificates and the 1980 National Infant Mortality Surveillance project. In 1960 there were 14,714 deaths due to congenital anomalies, compared with 8,674 in 1980, a 41 percent reduction. The infant mortality risk (IMR) due to congenital anomalies fell 31 percent. This is in contrast with the observed 54 percent decline in IMR due to all causes. This reduction in mortality due to congenital anomalies occurred for both whites and blacks in the postneonatal period and for whites only in the neonatal period. Changes ranged from a 1.8 percent increase for the black neonatal mortality risk to a 46.6 percent decrease for the white postneonatal mortality risk. In spite of these relative reductions, the absolute percentage of all infant deaths due to congenital anomalies had increased from 15.8 percent in 1960 to 24.1 percent in 1980. Two categories, cardiovascular and central nervous system anomalies, accounted for 72 percent of infant deaths due to congenital anomalies in 1960 and for 59 percent in 1980; cardiovascular anomalies accounted for 48 percent of all deaths due to congenital anomalies in 1960 and 40 percent in 1980. Infant mortality risks in the United States showed a 2:1 black to white ratio in both 1960 and 1980. However, for infant mortality due to congenital anomalies, the black and white mortality risks were approximately equal in both 1960 and 1980. For infants with birth weights of 500-2,499 g, the risk of neonatal mortality for blacks was less than half the risk for whites. PMID- 3104975 TI - Differences in neonatal and postneonatal mortality by race, birth weight, and gestational age. AB - In recent decades, neonatal and postneonatal mortality rates have declined overall in the United States. Yet, the mortality rates for black infants continue to be approximately twice those for white infants. With the use of data from 45 of the 53 vital statistics reporting areas that participated in the 1980 National Infant Mortality Surveillance project, we extended previous State analyses to describe differences, nationally, in neonatal and postneonatal mortality risks for black and white infants according to gestational age and birth weight. After restricting our analysis to single-delivery infants with known and plausible combinations of gestational age of 26 or more weeks and birth weights of 500 grams (g) or more, the neonatal mortality risk (NMR)--that is, the number of deaths to infants less than 28 days of life per 1,000 live births--for black infants was 1.6 times higher than the NMR for whites. This difference was largely explained by two findings: First, although the NMR was lower for black than for white infants with gestational ages of less than 38 weeks and birth weights less than 3,000 g, that advantage was heavily outweighed by the higher percentage of such births among blacks, accounting for roughly two-thirds of the overall difference in NMR between blacks and whites. Second, most of the remaining difference in NMR was accounted for by higher NMRs among black infants with gestational ages of 38 or more weeks and birth weights of 3,000 g or more. A comparison of the lowest mortality risk for any combination of birth weight and gestational age showed that the black NMR was 1.89 times higher than the white NMR. The postneonatal mortality risk (PNMR)--PNMR equals the number of deaths to infants 28 days to less than 1 year of life per 1,000 neonatal survivors--for black infants was 2.09 times the PNMR for white infants. Black infants had higher PNMRs than white infants for nearly all combinations of birth weight and gestational age. Higher PNMRs among infants with gestational ages of 38 or more weeks and birth weights of 2,500 g or more accounted for 43 percent of the difference in PNMR between black infants and white infants. Eliminating the U.S. black-white infant mortality disparity will require not only reducing the higher frequency of prematurity and low birth weight among black infants, but also improving the survival during both the neonatal and postneonatal periods of term black infants with normal birth weights. PMID- 3104976 TI - Young maternal age and infant mortality: the role of low birth weight. AB - In 1980, there were 562,330 babies born in the United States to teenage mothers (19 years of age or younger). The offspring of teenage mothers have long been known to be at increased risk of infant mortality, largely because of their high prevalence of low birth weight (less than 2,500 grams). We used data from the National Infant Mortality Surveillance (NIMS) project to examine the effect of young maternal age and low birth weight on infant mortality among infants born in 1980 to U.S. residents. This analysis was restricted to single-delivery babies who were either black or white, who were born to mothers ages 10-29 years, and who were born in one of 48 States or the District of Columbia. Included were 2,527,813 births and 28,499 deaths (data from Maine and Texas were excluded for technical reasons). Direct standardization was used to calculate the relative risks, adjusted for birth weight, of neonatal mortality (less than 28 days of life) and postneonatal mortality (28 days to less than 1 year of life) by race and maternal age. There was a strong association between young maternal age and high infant mortality and between young maternal age and a high prevalence of low birth weight. Neonatal mortality declined steadily with increasing maternal age. After adjusting for birth weight, the race-specific relative risks for babies born to mothers less than 16 years of age were still elevated from 11 to 40 percent, compared with babies born to mothers 25-29 years of age. Otherwise, all the relative risks were nearly equal to 1. By contrast, most of the association between young maternal age and postneonatal mortality persisted after birth weight adjustment in all maternal age groups.These results suggest that the prevention of neonatal mortality and, to a lesser extent, postneonatal mortality among babies born to teenagers depends on preventing low birth weight. The prevention of postneonatal mortality may depend more on other factors, such as assisting teenagers with better parenting. Finally, although there maybe few biological reasons to postpone childbearing,teenage childbearing continues to place the mother and her baby at a social disadvantage. PMID- 3104977 TI - Analysis of unlinked infant death certificates from the NIMS project. AB - The National Infant Mortality Surveillance (NIMS) project used linked birth and infant death certificates to calculate birth weight-specific infant mortality risks for the 1980 U.S. birth cohort. Record linkage depends on complete registration of vital events, interstate exchange of vital records, accurate information on certificates, and a comprehensive linkage system. States reported 2,604 unlinked infant death certificates for 1980, ranging from 0 to 397 per State. Age at death for these infants ranged from 1 minute to 11 months. More than 41 percent of the unlinked death certificates were for postneonates, compared with 32.5 percent found in the cohort's total infant death experience. Only 38.2 percent of the unlinked infant death certificates showed strictly intrastate events (birth and death occurrence, and residence at death all in one State), compared with 92.9 percent in the cohort's total infant death experience. Estimates of the percentage successfully linked by State ranged from 86.0 to 100.0. After adjusting for the certainly unlinked infant death certificates, nine States' infant mortality risks increased by more than 0.2 per 1,000 live births. Improvements are needed both within and between States to ensure more complete birth and infant death certificate linkage. PMID- 3104979 TI - Using linked birth and infant death files for program planning and evaluation: NIMS workshop lessons. AB - Health planners should base program decisions on the best information available. Combining information from different sources can be valuable in identifying problems--the essential first step in program planning. To facilitate this process, a workshop was conducted during the National Infant Mortality Surveillance Conference in Atlanta, GA. Maternal and child health directors explored the use of linked birth and infant death data for program planning and evaluation. Linked birth and infant death certificate files permit evaluation of infant mortality by birth weight and other infant and maternal characteristics, thus providing more detailed information than birth or death certificates alone. An assessment of the birth weight distribution of live births, birth weight specific-mortality risks, distribution of deaths by birth weight, and birth weight-specific causes of death can help identify problems in the childbearing population and with the delivery of health services. Once the infant health problems are defined clearly, the selection and delivery of services can be better targeted and evaluated for the reduction of these problems. PMID- 3104978 TI - Experiences with linked birth and infant death certificates from the NIMS project. AB - The National Infant Mortality Surveillance (NIMS) project aggregated data provided by 53 vital statistics reporting areas--50 States, New York City, the District of Columbia, and Puerto Rico (subsequently called States)--from their files of linked birth and death certificates and compared individual States' total infant mortality experiences for the 1980 birth cohort by age at death, race, birth weight, and plurality. Therefore, it was essential to achieve maximum uniformity among the separate data sets and to specify when this uniformity could not be obtained. In working with these multiple sources, we identified five key issues that relate to data from linked birth and death certificates: Variations in definitions of variables are often embedded in data that have been gathered from several independent sources. (For NIMS, the sources were 53 reporting areas and the National Center for Health Statistics.) Variations in States' linking procedures--these are based on an individual State's primary purpose for linking the data--affect the completeness and comparability of the 1980 resident birth cohorts used for NIMS. Variations in the recording of some pregnancy outcomes as fetal deaths or live births are known to be a problem in vital statistics data that particularly affects data for events among infants weighing less than 500 g at birth. Ambiguities occur frequently in unknowns or zero values. For NIMS this effect was most pronounced for the pregnancy history variables. Examination of the values reported for unknown or zero categories helps in uncovering problems with and improving quality of data. (e) Analysis from a new perspective may reveal unexpected data problems. These problems tend to surface only during a reexamination of underlying data that is prompted by unusual findings.Continued alertness to these issues may improve further the quality of data in files of linked birth and death certificates and assure the integrity of analysis based on these data. PMID- 3104980 TI - The NCHS pilot project to link birth and infant death records: stage 1. AB - The National Center for Health Statistics (NCHS) has completed a pilot test of its method to develop national linked files of birth and infant death records. A linked file of the 1982 birth cohort was produced that successfully linked 97 percent of the death records for infants who died in a nine-State area. The method NCHS uses to create national linked files takes full advantage of two existing data sources: the NCHS fully coded natality and mortality files and State files of matched births and infant deaths. For the nine-State pilot area, NCHS obtained computerized linked files from the States and extracted from them the certificate numbers on matching birth and death records. With the use of these numbers, NCHS selected and linked birth and death statistical records from its final natality and mortality files, thus creating new statistical linked records. The initial match rate of 93.2 percent for the project's linked record file was increased to 96.7 percent as a result of efforts by the pilot States to complete the matching of birth and infant death records. Matching in the nine State linked file appears to be highly accurate, based on the results of two evaluation studies. In the second stage of the project, now underway, NCHS will continue to evaluate and improve State and national linked files for the four birth cohorts of 1983-86. With funding from the Department of Health and Human Services' Office of the Assistant Secretary for Planning and Evaluation, stage 2 will be conducted in collaboration with each of the 50 States, the District of Columbia, Puerto Rico, the Virgin Islands, and New York City, an independent registration area. PMID- 3104981 TI - Acquired immunodeficiency syndrome and black Americans: special psychosocial issues. AB - Approximately 25 percent of persons diagnosed with acquired immunodeficiency syndrome (AIDS) have been black. This paper examines three areas of concern when focusing on AIDS in the black population: differences from whites in patterns of transmission of the infection, cultural factors that may affect health education efforts, and ethnically relevant issues in the provision of medical care to black persons with AIDS. Recognition of these differences is important in developing appropriate AIDS-related services for the black population. First, the epidemiologic pattern of infection in the black population differs from whites. Although they represent only 12 percent of the American population, blacks make up nearly one-quarter of reported AIDS cases. Currently, it is estimated that between 1 and 1.4 percent of the black population may be infected with the human T-lymphotropic virus/lymphadenopathy-associated virus (HTLV-III/LAV), a rate estimated to be three times that of whites. In addition, epidemiologic patterns of viral transmission in the black community suggest a greater incursion into the heterosexual population. Second, educational interventions designed to slow the rate of infection need to be sensitive to cultural and behavioral differences between blacks and whites who are at increased risk for acquiring or transmitting an HTLV-III/LAV infection. These include possible differences in perceptions of being at risk and actual risk behaviors. Third, in caring for black AIDS patients there are psychological, sociocultural, and medical care issues that are relevant. Research findings specific to health care for blacks are reviewed with particular reference to concerns that might arise in the treatment of black persons with AIDS. Recommendations for research and health education efforts in the black community are presented. PMID- 3104982 TI - Age- and sex-related blood cell values in healthy black Americans. AB - Hemoglobin, mean corpuscular volume, erythrocyte count, and leukocyte count were measured, and hematocrit, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were computed electronically for 7,739 healthy black persons. The study population comprised 3,393 males and 4,346 females 1-84 years of age, all from the Washington, DC, metropolitan area. Persons with sickle cell disease and elevated hemoglobin F were excluded from analysis, but those with traits for hemoglobin S, C, and thalassemia were not. Mean and percentile values are presented in tabular form. Hemoglobin, hematocrit, and mean corpuscular volumes were lower than those reported in surveys of white populations. Beginning with the 11-15-year age groups, black males had higher red cell values than black females. After age 30, mean hemoglobin levels for men gradually declined, while those in women rose, so that the sex difference diminished after 60 years of age. Leukocyte counts were higher in young children and in women, compared with men ages 21-50 years. After 60 years of age, the sex difference disappeared. Further large surveys that exclude data on persons with iron deficiency are needed in black populations. PMID- 3104983 TI - The effect of a metabolic inhibitor upon the properties of the cerebral vasculature during a whole-head saline perfusion of the rat. AB - The effect of the metabolic inhibitor 2,4-dinitrophenol (DNP) has been assessed during a simple in situ Ringer solution perfusion of the rat brain. The preparation was perfused, with or without the addition of DNP, for periods ranging up to 30 min. Following this pre-test perfusion, both the vascular permeability and cerebral perfusate flow were assessed. In the absence of DNP significant barrier disruption had taken place by 10 min and the flow rates showed greater fluctuations with time. In the presence of DNP, however, perfusate flow remained constant and the blood-brain barrier remained intact to [14C]mannitol for at least 10 min, but subsequently the flow rate dropped and the barrier began to show evidence of disruption. The unbound visual marker, Evans Blue, was apparently excluded from all regions other than those that are known to lack a blood-brain barrier. The water content of the brain showed no significant increase until 20 min. Patency of the capillaries was demonstrated by direct visualization of the cerebral vasculature with an Indian ink-gelatin mixture and in some animals there was evidence of incomplete filling following 30 min of perfusion. It is concluded that the use of DNP in the perfusate provides a useful preparation for the short-term study of passive properties of the blood-brain barrier, such as carrier-facilitated diffusion, as well as mechanisms of barrier opening. PMID- 3104984 TI - Unilateral T cell maturation arrest in the thymus of CBA/H mice as a long-term effect after neutron irradiation. AB - Thymuses of CBA/H mice were investigated up to 570 days after whole-body irradiation with 2.5 Gy fast fission neutrons or 6.0 Gy X rays. A number of these thymuses, observed 220-270 days after neutron irradiation, have two equal sized lobes, one of which has an abnormal T cell distribution. The present paper reports on the distribution of lymphoid and stromal cell types in these thymuses. For this purpose, we employed immunohistology using the indirect immunoperoxidase method. We incubated frozen sections of these aberrant thymuses with monoclonal antibodies directed to cell surface differentiation antigens on lymphoid cells, such as Thy-1, T-200, MT-4, Lyt-1, Lyt-2, and MEL-14; monoclonal antibodies directed to major histocompatibility complex (MHC) antigens, such as I-A and H 2K; and monoclonal antibodies directed to determinants in various thymic stromal cell types. The results of this study show a T cell differentiation arrest in only one of the two thymic lobes. T cells in the aberrant lobe express Thy-1, T 200, and MEL-14 antigens but are MT-4- and Lyt-1-. In some lobes, a weak Lyt-2 expression was observed. The observed T cell maturation arrest is mainly restricted to the cortex since in the medulla, in addition to cells with an aberrant cortical phenotype, normal T cell phenotypes are observed. This indicates that cortex and medulla have independent generation kinetics in T cell maturation. The stromal cell composition in these abnormal lobes is not different from that in the normal lobe, but the size of the medulla tends to be smaller. Furthermore, the I-A expression on the cortical epithelial cells does not reveal the characteristic reticular staining pattern that is observed in the normal lobe, since the I-A determinants are not strictly confined to the epithelial cells. In addition, cortical lymphoid and stromal cells in these lobes are slightly H-2K+. These alterations in MHC expression in the cortex are discussed in relation to the observed T cell maturation arrest. PMID- 3104985 TI - Low attenuation material for table tops, cassettes and grids: a review. PMID- 3104986 TI - Tissue-type plasminogen activator (t-PA) and single chain urokinase-type plasminogen activator (scu-PA): potential for fibrin-specific thrombolytic therapy. PMID- 3104987 TI - Desmopressin (DDAVP) for treatment of disorders of hemostasis. AB - At a time when the acquired immunodeficiency syndrome as well as hepatitis and other blood-borne diseases are a threat to patients with bleeding disorders who need treatment with blood products, it is rewarding to realize that a number of these patients can be safely and effectively treated with their own desmopressin stimulated F.VIII:C and vWF. Desmopressin is clinically useful for treatment of patients with moderate and mild hemophilia. The limits of the clinical indications are established by the nature of the bleeding episode, the resting factor level, the level that must be achieved, and the length of time the level must be maintained to manage any given bleeding episode. In von Willebrand disease, desmopressin can be used more extensively to raise F.VIII:C levels than in classic hemophilia, because fewer of the patients have the severe form of the disease that is unresponsive to desmopressin. Increases in the level of F.VIII:C of about four times the resting value can be expected both in hemophilia and von Willebrand disease, but it must be borne in mind that the range of individual responses is large. Even though it is not easy to correct the prolonged bleeding time, particularly in patients with dysfunctional vWF, this drawback is of clinical relevance only in a minority of cases. A role for the use of desmopressin in acquired diseases of primary hemostasis has been proposed more recently, and experience is more limited than in congenital bleeding disorders. Uremia is probably the most firmly established indication because it has been shown that the bleeding time is often dramatically shortened by desmopressin, and hemorrhages can be stopped or prevented before surgical procedures. The indications for use of the compound in liver cirrhosis and congenital and acquired platelet dysfunctions are promising but much less established from a clinical standpoint. The bulk of available clinical experience is based on intravenous administration. Intranasal and subcutaneous administration have been successfully attempted and might be more convenient in selected circumstances, such as home treatment and the stimulation of blood donors to provide more abundant supplies of F.VIII:C and vWF. However, the responses after intranasal administration are less predictable and consistent than after intravenous administration. Desmopressin has few troublesome side-effects. Mild facial flushing, a small increase in heart rate, and, more rarely, mild headache can occur transiently during infusion. Signs of hyponatremia or cerebral edema are extremely rare, providing that excessive fluid intake is avoided.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3104988 TI - Factor VIII structure and proteolytic processing. PMID- 3104989 TI - [Isolation and structural characterization of ovarian follicular fluid inhibin]. PMID- 3104990 TI - Isolation of the cDNA for human prostaglandin H synthase. AB - Prostaglandin H Synthase (PGHS, cyclooxygenase) is a 67 kd protein which catalyzes the first step in prostaglandin synthesis. The primary amino acid sequence and the molecular mechanisms regulating expression are unknown. We report here isolation of a cDNA clone for the enzyme from human vascular endothelial cells for use in such studies. High titre, polyclonal antiserum against PGHS was developed in rabbits. The antiserum was monospecific, reacted with cyclooxygenase on Western blots at a limiting dilution of 1:500,000 and immunoprecipitated cyclooxygenase synthesized by in vitro translation of PGHS messenger RNA. It was used to screen a lambda gt11 cDNA expression library from human endothelial cells. Three positive clones were isolated. Following plaque purification, one clone reacted strongly with two other polyclonal antisera independently raised against highly purified cyclooxygenase and the aspirin acetylated enzyme. Western blot analysis confirmed production of a large approximately 180 kd fusion protein of cyclooxygenase and beta-galactosidase. The cDNA insert of approximately 2.2 kilo base pairs was excised and subcloned into plasmid pUC8. A 24 nucleotide DNA probe, synthesized according to the amino acid sequence of the aspirin-acetylation site of cyclooxygenase, hybridized strongly with the 2.2 kbp cDNA insert. It is concluded that the 2.2 kbp cDNA insert represents a cDNA clone for human cyclooxygenase, which also expresses the aspirin-acetylation site. This is the first reported isolation of the cDNA for this enzyme, and will facilitate further studies on the primary sequence and on the regulation of the enzyme at the molecular level. PMID- 3104992 TI - Effects of heavy metal ions on phospholipid metabolism in human neutrophils: relationship to ionophore-mediated cytotoxicity. AB - This study examined the effects of 0.1mM heavy metal ions (Au3+, Zn2+, Cr3+, Mn2+, and Cu2+) on ionophore-treated human neutrophils. Treatment of human neutrophils with 5-10 microM ionophore A23187 resulted in phospholipid deacylation and eicosanoid release within 5 min. After approximately 20 min, viability decreased significantly with near total cell death by 50 min. Heavy metal ions altered phospholipid metabolism, eicosanoid synthesis, and cytotoxicity in parallel fashion. Radioimmunoassays for 5-HETE and LTB4 demonstrated that Au3+ and Zn2+ stimulated, Cr3+ had little effect on, and Mn2+ and Cu2+ inhibited eicosanoid release from ionophore-treated neutrophils. Cells prelabelled with [3H]arachidonic acid exhibited similar metal-mediated effects on lipid metabolism. Strong negative correlations between metal effects on viability and the metabolism of arachidonic acid suggest that eicosanoids participate in ionophore-induced cytotoxicity. PMID- 3104991 TI - Stimulation of HCO3- secretion by the prostaglandin E2 analog enprostil: studies in human stomach and rat duodenum. AB - This study investigated the action of enprostil, a synthetic analog of PGE2, on gastric HCO3- secretion in humans and on duodenal HCO3- secretion in the anesthetized rat. A previously validated 2-component model was used to calculate gastric HCO3- and H+ secretion in 10 human subjects. Compared to placebo, a single 70 micrograms oral dose of enprostil increased basal gastric HCO3- secretion from 1810 +/- 340 to 3190 +/- 890 mumol/hr (P less than 0.05). In addition, enprostil reduced basal gastric H+ secretion from 5240 +/- 1140 to 1680 +/- 530 mumol/hr (P less than 0.02). Enprostil also increased HCO3- secretion and reduced H+ secretion during intravenous pentagastrin infusion. In the rat, duodenal HCO3- secretion was measured by direct titration in situ using perfused segments of duodenum just distal to the Brunner gland area and devoid of pancreatic and biliary secretions. Addition of enprostil (10 micrograms/ml) to the duodenal bathing solution increased duodenal HCO3- secretion from 6.3 +/- 1.3 to 15.1 +/- 2.0 mumol/cm X hr (P less than 0.01, n = 6). The stimulatory action of enprostil on duodenal HCO3- secretion at 10 micrograms/ml was comparable in magnitude and duration to that of 10 micrograms/ml natural PGE2. In summary, the PGE2 analog enprostil stimulated gastroduodenal HCO3- secretion, effects which may be beneficial in protection of the gastroduodenal mucosa against luminal acid. PMID- 3104993 TI - The Alamata experience. PMID- 3104994 TI - Back injuries: Part 2. The stories behind the statistics. PMID- 3104995 TI - Preceptor programmes: one answer to the professional development needs of nurses. Part One. PMID- 3104996 TI - Influence of scattered radiation on heterogeneity correction in three-dimensional treatment planning. AB - The first and multiple scattered radiations of 60Co gamma rays and 10 MV X-rays were measured using an ionization chamber, and the values obtained were compared with the calculated values. The experimental values of the angle distributions of the first scattered photons from tissue-equivalent materials in free space agreed well with the theoretical values calculated from the Klein-Nishina probability in the compton scattering process. However, the scattered radiation in phantoms was not represented by only the first scatter components. The results indicate that the weighting factor of all scattered radiations in the calculated three dimensional dose distribution can be set by the inverse square correction for the distance from the scattering point to the reference point within an accuracy required in clinical dosimetry. The present method provides a simple and practical approach to obtaining the computation speed in three-dimensional treatment planning. PMID- 3104998 TI - Practice of 3-dimensional treatment planning at the Fox Chase Cancer Center, University of Pennsylvania. AB - The use of 3-dimensional (3-D) dose distributions and dose-volume histograms in radiation therapy treatment planning is illustrated on a patient with a head and neck tumor. The patient was immobilized in a rectangular tissue compensation bolus box. The treatment was planned with a 14 MeV D-T derived fast neutron therapy beam. The isodose distributions and the dose-volume histograms at multiple adjacent levels are used to evaluate the adequacy of coverage of target volumes and the doses to the normal tissues. Such dose-volume histograms are useful and practical in summarizing the dose distribution throughout the irradiated volume, assessing the degree of uniformity of the dose distribution within the target volume, quantifying the amount of normal tissue irradiated, and evaluating rival treatment plans for both particle and nonparticle beams. PMID- 3104997 TI - Dosimetry comparison between interstitial and intracavitary irradiation in the treatment of uterine cervix cancer. AB - Locally advanced carcinoma of the uterine cervix, and carcinoma of the cervical stump are managed primarily by endocurietherapy [ECT] combined with external-beam pelvic irradiation. Two afterloading techniques of endocurietherapy are used, first, the intracavitary technique with 137Cesium, and second, the interstitial technique with 192Iridium. Because of displacement of the bladder and rectum away from the applicator in intracavitary ECT, compared to interstitial ECT where vaginal packing cannot be used, the rectal and bladder reference point doses are much lower. The use of the interstitial endocurietherapy technique should be limited to specific presentations where the distorted anatomy does not permit good intracavitary dosimetry in cases of locally advanced cervical and cervical stump cancers. A higher risk of major bowel and bladder complications must be accepted in order to achieve local tumor control if the Transperineal Template 192Iridium Endocurietherapy is required and used. PMID- 3104999 TI - Fibroblast growth factor as an intraovarian hormone: differential regulation of steroidogenesis by an angiogenic factor. AB - The potential role of fibroblast growth factor (FGF) in the regulation of granulosa cell differentiation was investigated because of its recent identification as the corpus luteum angiogenic factor. Treatment of rat ovarian granulosa cells with FGF inhibits the capacity of follicle stimulating hormone to stimulate estrogen production and to induce luteinizing hormone receptors. In contrast, although incubations with FGF can inhibit the estrogen-sensitive component of progesterone synthesis, the presence of FGF with suboptimal concentrations of follicle stimulating hormone significantly enhances the synthesis of progesterone. This capacity to differentially regulate steroidogenesis in the granulosa cell is comparable to the potency of FGF (ED50 = 30 pg/ml, 10(-12) M) in other in vitro assays. The observation that an angiogenic factor, like FGF, can specifically increase the sensitivity of progesterone synthesis and simultaneously inhibit estrogen formation supports the hypothesis that this growth factor plays an important role in the development and maintenance of a functional corpus luteum. As such, FGF may be involved in the local regulation of follicular selection, growth and atresia by simple virtue of its capacity to induce a neovascular response on one hand and by its ability to modulate the differentiated response to gonadotropins on the other. PMID- 3105000 TI - Automated 13CO2 analyzing system for the 13C breath test. AB - An automated 13CO2 analyzing system for the 13C breath test was designed, built and evaluated. The system, which was designed to be controlled by a micro computer, includes CO2 purification, 13CO2 abundance measurement, data processing and data filing. This article gives the description of the whole system with flow charts. This system has proved to work well and it has become feasible to dispose of 5 to 6 CO2 samples per hour. With such a system, the 13C breath test will be carried out much more easily and will obtain much greater popularity. PMID- 3105001 TI - [Morpho-functional evaluation of the small intestine patients with Crohn disease. Enema of the small intestine versus post-heparin plasma diamine oxidase]. AB - Our study was directed not only towards the diagnosis of small bowel Crohn's disease, but especially to a quantitative analysis, for a correct therapeutical approach. This experimental trial is based on the relationship between radiological evidence, measured during small bowel enema, and the seriousness of the morphological and functional damage to the intestinal mucosal membrane, evaluated with a post-heparin diamine-oxidase activity test. With this method we studied 35 selected patients; 16 of them were affected by the disease with an exclusive localization in the small bowel and 5 have been considered separately, because 3 patients had already been operated and the other 2 showed different localizations. In our results, the two parameters were not constantly related to each other. In other words the enema's morphological data sometimes do not accord with the mucosal membrane integrity index expressed by the enzyme. Anyway the importance of this study is the attempt of making an objective comparison between an anatomic situation and its functional consequence. These aspects have a great significance in Crohn's disease. PMID- 3105002 TI - [Evaluation of EDTA and its clinical use as an irrigating solution for root canals]. PMID- 3105003 TI - [Non-A, non-B hepatitis]. PMID- 3105004 TI - [Thrombotic phenomena and lupus anticoagulant in a series of 112 patients with systemic lupus erythematosus]. PMID- 3105006 TI - [Classification of Mycobacterium tuberculosis by phage typing markers in the City of Havana province]. PMID- 3105005 TI - [Schistosomiasis mansoni in Cuban patients. A clinical study of the first 4 cases imported from the People's Republic of Angola]. PMID- 3105007 TI - [Estimation of the impact of the principal diseases in rural Mali]. AB - The authors assess the health impact of major diseases in the circles of Kita, Bafoulabe and Kenieba (Western Mali) by measuring, for each of them, the number of healthy days of life lost through illness, disability and death. Malaria, birth diseases, infant gastro-enteritis and pneumopathies, measles, malnutrition and hemoglobinopathies account for 58.1% of healthy life lost due to all studied diseases. Parasitic diseases (except malaria), tuberculosis, leprosy are less important than usually said; on the contrary, the impact of hepatic, cardiovascular, and eyes diseases is great. In developing countries assessing the number of healthy days lost by the community due to different diseases is usefull to choose the health priorities and to compare the cost/effectiveness ratio of different health programs. PMID- 3105008 TI - [CO2 arterio-alveolar gradient in anesthesized patients]. PMID- 3105010 TI - [Intrahepatic cholestasis associated with light-chain deposition disease]. PMID- 3105009 TI - [Changes in the final expiratory fraction of CO2 after ischemia release]. PMID- 3105011 TI - Ca2+-dependent K+ transport in lymphocytes. AB - The treatment of rat thymocytes with A23187 + Ca2+, ascorbate-phenazine methosulphate or propranolol induced quinine-sensitive fluxes of K+ (Rb+) suggesting the presence in the cell membrane of Ca2+-dependent K+ channels. Concanavalin A induced K+ channel activation only at very high doses (13 micrograms/ml). Neither quinine nor the increase of the K+ concentration in the medium to 30 mM prevented the stimulation of amino acid transport induced by concanavalin A, suggesting that the Ca2+-dependent K+ channel is not involved in the early phenomena of lymphocyte activation. PMID- 3105013 TI - Medicaid elders in a rehabilitative trajectory. PMID- 3105012 TI - [Pseudothrombocytopenia and pseudoleukocytosis. Study of 17 cases of EDTA dependent platelet agglutination]. PMID- 3105014 TI - [Control of ingestive behavior and rumination by neuropeptides]. AB - In sheep as in other species, intracerebroventricular (ICV) administration of picomolar doses of several peptide hormones affects food intake and rumination, suggesting that these hormones play a role in the physiological control of feeding behavior. Their effects depend on their duration (short vs long-term) and/or their nature (orexigenic vs anorexigenic). Among the short-term satiety factors, CCK8, CRF and calcitonin, administered ICV, decrease food intake by reducing the rate (CCK8) or the duration (CRF, calcitonin) of ingestion; in contrast, the gastrin group of peptides (gastrin 17, penta or tetragastrin) reduces food intake by promoting an early period of rumination. Opioid peptides such as Met-enkephalin and Dynorphin initiate food intake in satiated sheep and are supposed to be active in the short-term regulation of food intake in these ruminants. In contrast both calcitonin gene-related peptide (CGRP) and growth hormone-releasing factor (GRF) increase the daily food intake, when ICV injected, but their centrally mediated orexigenic effects depend on the regimen and the digestive status. These results confirm the species differences observed in food intake regulation and the major role of the C.N.S. in controlling feeding behavior and energy balance in ruminants. PMID- 3105015 TI - Role of inflammation in asthma. PMID- 3105016 TI - The function and properties of human lung mast cells. AB - Mast cells may be recovered from human subjects by bronchoalveolar lavage. Such bronchoalveolar mast cells will release histamine in response to IgE-dependent challenge in a reaction that is dose-, time- and energy-dependent. They possess functional characteristics distinct from dispersed human lung mast cells. The percentage of mast cells within the bronchoalveolar cell population is critically dependent upon the underlying pathology. Greater numbers of mast cells may be recovered from the bronchoalveolar compartment of extrinsic asthmatics than from controls. In addition, bronchoalveolar mast cells from asthmatic subjects show an increased releasability of histamine in response to anti-IgE. Antigen challenge also leads to the release of histamine in vitro, demonstrating the potential for the antigen-specific initiation of bronchoconstriction in these subjects. Spontaneous release of histamine from bronchoalveolar mast cells of asthmatic subjects was also greater than in controls (up to 46%), a feature which may be related to non-immunological mechanisms of bronchoconstriction. Such non immunological mechanisms have been further investigated utilising mannitol as a model of hyperosmolar histamine release. Mannitol induced a dose-dependent release of histamine from bronchoalveolar mast cells of normal subjects, and this release was significantly inhibited by sodium cromoglycate. The leukotrienes are putative major mediators of human asthma. After challenge with anti-IgE in vitro, dose-dependent release of leukotriene C4 and prostaglandin D2 occurs from the bronchoalveolar cells of normal subjects. The release of PGD2 shows significant correlation with histamine release. Lying superficially, bronchoalveolar mast cells would be readily accessible to inhaled antigen. Mediator release from such cells may be relevant to the pathogenesis of asthma. PMID- 3105018 TI - [Pigeon-breeder's disease. Presentation of 5 cases]. PMID- 3105017 TI - [Gonadotropin secretion in congenital adrenal hyperplasia before and during glucocorticoid therapy. Differences between the newborn infant and late onset forms]. PMID- 3105019 TI - The role of interstitial implantation in the treatment of primary breast cancer. PMID- 3105020 TI - [The prevention of asthma: goals, methods, results]. PMID- 3105021 TI - Sleep apnea and autonomic cerebrovascular dysfunction. AB - Changes in common carotid blood flow (CCF) and resistance index (RI), calculated from velocity waveforms by a noninvasive pulsed Doppler technique, were measured during apneic episodes and voluntary breath holding in five sleep apnea patients (SA) and during breath holding in five normal subjects (N). During apneic episodes averaging 27 s, CCF was reduced by 9% and RI increased by 4%, both trends being related to apneic duration. Internal carotid artery measurements in one SA indicated more dramatic changes in blood flow and RI than noted in CCF. During breath holding, CCF decreased significantly in SA but not in N, and RI showed a smaller reduction in SA. These changes in CCF and RI during sleep apnea are similar to those noted in anesthetized dogs where vasomotor waves and associated apneas were induced by elevating intracranial pressure. Previously reported recordings of ventilatory and systemic cardiovascular responses in SA are similar to these recordings in dogs, and it is therefore proposed that vasomotor responses to intermittent cerebral ischemia and hypercapnia may be the principle event in SA and periodic breathing only a secondary consequence of the prevailing autonomic dysfunction. PMID- 3105022 TI - [Cardiomyopathies in children. III]. PMID- 3105023 TI - [Prenatal factors implicated in infant pathology]. PMID- 3105024 TI - [Diagnosis of vaginitis in girls]. PMID- 3105025 TI - [Acute opium poppy poisoning in children]. PMID- 3105026 TI - [Therapeutic aspects of juvenile bronchial asthma. II]. PMID- 3105027 TI - [Critical comments on the current treatment of neonatal hemolytic diseases due to anti-Rh(D) isoimmunization]. PMID- 3105028 TI - [Use of nonspecific immunotherapy in pediatric practice]. PMID- 3105029 TI - [Optimization of nutrition for premature infants using essential fatty acids]. PMID- 3105030 TI - [Chagas' megacolon: considerations on new physiopathological perspectives]. PMID- 3105031 TI - [Blood gastrin curves: difference of behavior to food stimulation in patients with hepatointestinal and hepatosplenic forms of schistosomiasis mansoni]. PMID- 3105032 TI - [Control of diabetes by transplants of islands of Langerhans prepared without the use of enzymatic digestion: experimental study in the rat]. PMID- 3105034 TI - [Crohn's disease]. PMID- 3105033 TI - [Post-antibiotic effect in the treatment of infections in neutropenic patients]. PMID- 3105035 TI - [Development of a hospital for extended care: the hospital of Youville in Sherbrooke (Canada)]. PMID- 3105036 TI - Infectivity of amastigotes of Trypanosoma cruzi. PMID- 3105037 TI - Dynamics of transmission of Trypanosoma cruzi in a rural area of Argentina. III. Persistence of T. cruzi parasitemia among canine reservoirs in a two-year follow up. PMID- 3105038 TI - [Immunological studies in hamsters (Cricetus auratus) infected with Schistosoma mansoni]. PMID- 3105039 TI - [Therapeutic evaluation of oltipraz in human S. mansoni infection]. PMID- 3105040 TI - Dialyzable transfer factor in experimental Chagas' disease: in vitro studies. AB - The dialyzable transfer factor (TF) was prepared from spleen and lymph node cells of either normal (TFn) or infected (TFi) mice with Trypanosoma cruzi. The ability of TFn and TFi in transferring cellular immunity to T. cruzi antigens was assessed by the macrophage migration inhibition assay and lymphocyte transformation test. The results obtained with these two immunological assays indicated that only TFi is able to transfer cellular immune responses. This phenomenon was antigen specific. The content of free amino acids in TFi preparation was higher than in TFn. However, our data indicated that the stimulation of lymphocyte transformation is not due to the increase in glycine and serine. This activity of TFi required the addition of T. cruzi antigens. Our findings support the hypothesis that TFi is derived from immune RNA. PMID- 3105041 TI - [Residue levels of polychlorinated biphenyls in fish muscles]. PMID- 3105042 TI - Effect of Gluma in acid-etched dentin cavities. AB - The marginal adaptation of a restorative resin in combination with a dentin bonding agent was investigated in dentin cavities treated either with a strong solution of phosphoric acid or with an 0.5 M EDTA solution neutralized to pH 7.4 with NaOH. It was found that both the maximum marginal contraction gap and the extent of the gap were significantly increased in acid-etched cavities when compared to cavities cleaned with the EDTA solution. PMID- 3105043 TI - Dentin-polymer bond established by Gluma and tested by thermal stress. AB - The walls of cylindrical cavities in human dentin were treated with Gluma and various resins before filling with either a microfilled or a macrofilled composite (Silux, P-30 or Concise). The extent of gaps (crevices) along the tooth/filling interface was observed before and after thermal cycling at restorations polished either 10 min or 24 h after curing of the composite. Application of a resin containing polymerization initiators and 1% propanal before filling with Silux or Concise resulted in restorations without contraction gaps along the tooth/filling interface. When P-30 was used in this procedure, one of six of the fillings exhibited gaps, but none of the six did so when removal of the marginal excess was postponed for 24 h. PMID- 3105044 TI - Induction of cytotoxic capacity by recombinant gamma interferon in human myelomonocytic leukaemia cell lines. AB - We have investigated the ability of human recombinant gamma interferon (IFN gamma) to induce functional differentiation in three human myelomonocytic cell lines U937, RC2A, and ML-2. Treatment with IFN-gamma induced natural killer (NK) cell like cytotoxicity against K-562 cells in ML-2 and RC2A but not in U937. U937 and RC2A displayed a spontaneous antibody-dependent cell-mediated cytotoxicity (ADCC), which against nucleated target cells was significantly increased in U937 but not in RC2A after treatment with IFN-gamma. ML-2 did not display ADCC against nucleated targets either before or after IFN-gamma treatment, but lysed efficiently antibody-coated erythrocytes. All three cell lines displayed enhanced ADCC against erythrocytes after IFN-gamma treatment. Spontaneous phagocytosis of erythrocytes was seen in U937, and this was enhanced by IFN-gamma treatment, while ML-2 and RC2A were phagocytically inactive before and after treatment with IFN-gamma. The differentiated functions induced by IFN-gamma treatment in this panel of phenotypically closely related cell lines offers an interesting model for further studies on the IFN-gamma regulated gene expression. Moreover, the increased cytolytic capacity after exposure to IFN-gamma might have implications on the use of IFN-gamma for treatment of myelomonocytic malignancies. In such cases, IFN-gamma might even increase the aggressiveness of the tumour. PMID- 3105046 TI - The emergence of resistance of Pseudomonas aeruginosa in patients treated with ceftazidime. PMID- 3105045 TI - Binding characteristics of human serum amyloid P component. AB - Serum amyloid P component (SAP), a normal human plasma glycoprotein, was found in a solid phase ELISA to have Ca2+-dependent binding for keyhole limpet haemocyanin (KLH), pectic acid, trinitrophenylated (TNP) macromolecules, and plastic surfaces. The binding to TNP-KLH was used to develop a sensitive ELISA. The binding of SAP to the ligands mentioned was inhibited by EDTA, KLH, pectic acid, TNP-conjugated macromolecules (bovine serum albumin, polyacrylhydrazide), and p nitrophenylarsonic acid. Underivatized and DNP-conjugated macromolecules did not inhibit the SAP binding; arsenilic acid, picric acid, and dinitrophenyl were weak inhibitors. SAP bound to TNP-agarose was eluated by either EDTA or p nitrophenylarsonic acid. Thus, a unique region of SAP is responsible for the polyspecific binding. We suggest that the polyspecific binding of SAP takes place through a Ca2+ bridge: half of the metal coordination sphere is occupied by SAP, with the other half available to interact with metal ligand. PMID- 3105047 TI - Endotoxin release from invasive meningococci related to sulfonamide resistance, serogroup and serotype. AB - The relationship between endotoxin liberation, sulfonamide resistance, serogroups and serotypes was studied in 28 Neisseria meningitidis strains isolated from patients with meningococcal disease. Sulfonamide resistance was present in 15/28 strains. 22 strains belonged to serogroup B, and 5 to group C; 1 strain was non groupable. Free endotoxin activity in growing cultures of meningococci with endotoxin titre of greater than or equal to 10(2) was found in 27/28 strains. A high endotoxin activity was present in both sulfonamide-sensitive and -resistant invasive meningococci. A high endotoxin release with titre greater than or equal to 10(3) seemed to be more associated with serogroup C than B, and more to the serotypes 2 and 15/16 than to the non-typable strains. PMID- 3105048 TI - Listeria monocytogenes meningitis in adults. Sixteen consecutive cases 1973-1982. AB - 16 adult patients with Listeria monocytogenes meningitis were reviewed to see whether clinical features or initial laboratory findings could discriminate between these patients and patients with purulent meningitis of other causes. Six patients suffered from known predisposing diseases and 4 were alcoholics. The initial clinical picture was indistinguishable from meningitis of other causes. Microscopy of cerebrospinal fluid (CSF) was negative in all cases but 2 where gram-positive rods were seen. CSF cytology and biochemistry could not discriminate from other causes of purulent meningitis although a low leucocyte content and a low percentage of neutrophils were often present. All L. monocytogenes strains isolated were sensitive to ampicillin and aminoglycosides whereas susceptibility to other antibiotics was low or varying. In adult patients suffering from purulent meningitis initial therapy should include ampicillin until an etiological diagnosis is established. The same is true in some cases of febrile encephalopathy with low content of neutrophils in CSF, especially when the glucose content is low. PMID- 3105049 TI - Strict protective isolation in allogenic bone marrow transplantation: effect on infectious complications, fever and graft versus host disease. AB - Complete microbial decontamination (laminar air flow room, sterile nursing and oral administration of cefamandole, gentamicin and nystatin) was carried out in 65 consecutive patients prior to allogeneic BMT for leukaemia (n = 58) or aplastic anaemia (n = 7). Very few microorganisms persisted during the post transplant treatment period, and the gut became sterile in all except for Candida in 11 patients. Six uncomplicated septicaemias, all with persistent organisms simultaneously present in the mouth (Pseudomonas 3, Serratia 1, Candida 2) occurred during a total of 1,360 days with granulocyte counts less than 0.5 X 10(9)/l. Post-transplant fever occurred in 52 patients, exceeding 40 degrees C in 25. Guided by the surveillance cultures only 46% of 43 unexplained febrile reactions were treated with systemic antimicrobials. Significant acute graft versus host disease (AGVHD) occurred in 14 (27%) of 52 patients receiving standard prophylaxis and HLA-matched grafts; immunosuppressive treatment was needed in 8 cases (16%). Thus, the additional costs of total microbial decontamination appear partially regained by a decreased morbidity and a reduced need for antimicrobial and immunosuppressive treatment, although neither fever nor AGVHD could be prevented. PMID- 3105051 TI - [Epidemiological study of severe vision impairment in Swiss children with special reference to retrolental fibroplasia]. AB - On December 31 1984, 262 children between 7 and 16 years of age were being trained in the major institutions for the visually handicapped in Switzerland. Of these, 173 (66%) were visually impaired and 89 (34%) were blind (i.e. some or no light perception). The causes of the visual impairment were malformations (65%), infectious diseases (14%), retrolental fibroplasia (12%), metabolic disorders (4%), tumors (3%) and accidents (2%). Among the blind children these diagnostic groups were distributed as follows: malformations (53%), RLF (25%), infections (10%), tumors (10%). The rates of blindness within The single diagnostic groups were as follows: accidents: 4 out of 5 children; tumors: 78%; RLF: 69%. This risk of developing blindness in RLF children, as compared to the risk in the overall population studied, had the highest statistical significance (p less than 0.0001). Malformations (28%) and infectious diseases (22%) represented a lower than average risk of developing blindness, the average figure for the whole population being 34%. The risk of developing blindness as a consequence of infections was statistically not different from that in the total population investigated. All RLF children had a birthweight below 2000 g. By extrapolation an incidence of 0.24% RLF cases was estimated for prematures below 2000 g. During the 10 years under investigation (1968-1977), 3.6 new cases of RLF/100,000 live births were diagnosed per year, with a peak in 1975 and 1976. This figure is probably an underestimate, since severely brain damaged blind children with multiple handicaps were not considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105050 TI - [Long-term problems of levodopa therapy in Parkinson disease]. AB - The dependence of motor side effects of L-DOPA therapy on clinical and pharmacodynamic parameters was investigated in 28 patients with Parkinson's disease. Duration of disease and degree of motor impairment were significantly less in a first group of 12 patients without motor side effects than in a second group of 16 patients with fluctuations of antiparkinsonian effects and dyskinesias. The two groups showed different pharmacodynamic patterns: the antiparkinsonian effect in the first group remained unchanged, with decreasing DOPA plasma concentrations (Type I), whereas in the second group a direct correlation between DOPA plasma levels and antiparkinsonian effect was observed (Type II). A possible mechanism for the different pharmacodynamic patterns and its relevance for therapy are discussed. PMID- 3105052 TI - [Non-specific chronic obstructive bronchopneumopathy and nutrition]. AB - Malnutrition is often observed in patients with chronic respiratory failure, particularly during acute episodes. In this short review, we discuss the nutritional status of patients suffering from chronic obstructive pulmonary disease (COPD) in the stable and acute phases, and the consequences of malnutrition for some components of the respiratory system (respiratory muscles, pulmonary tissue and ventilation control). Finally we propose a realimentation protocol, although at present time there is no proof that renutrition influences short or long term prognosis in such patients. PMID- 3105053 TI - [Retrospective (1970-1984) serological study of delta antigen and antibody. Observations on seroconversion and absence of delta in non-A, non-B hepatitis]. AB - 335 serum samples collected between 1970 and 1984 from 278 HBsAg positive patients were tested for HDV antigen and HDV antibody (HDV = hepatitis D virus; also referred to as delta virus). The first positive sample was obtained in February 1974. The prevalence of the delta coinfection fluctuated in the following years between 0 and 52% of HBV-infected subjects. It was 40% on average in subjects at risk for HBV infection (i.v. drug abusers, homosexuals and institutionalized mentally retarded subjects) and 6% in persons without risk factors. The antibody was also found in 22% of subjects in a group of drug abusers who recovered from HBV infection (positive for anti-HBs antibody). The study showed that dissemination of HDV infection in Switzerland after 1974 was small clusters occurring mainly in drug users. It also showed that the infection was principally associated with chronic active hepatitis. In addition, sequential serum samples were taken from five patients with chronic hepatitis B superinfected by HDV, over periods of 2 to 13 months. Seroconversion (HDV antigen to HDV antibody) was observed in 4 of these 5 patients, with simultaneous presence of antigen and antibody for periods of 2 to 6 weeks. 167 samples from patients with non-A, non-B hepatitis were all negative for anti-delta antibody. PMID- 3105054 TI - An unusual case of diarrhoea during enteral nutrition. AB - An unusual case of diarrhoea during enteral nutrition is reported. Disintegration of the capsule of a mercury-tipped enteric feeding tube resulted in spillage of mercury into the small intestine. This fault was discovered some days later when the tube was removed due to coincidental blockage of its lumen. PMID- 3105055 TI - Nutritional and metabolic support following acute hepatic trauma. AB - A patient undergoing partial hepatectomy subsequent to trauma was maintained post operatively on a specifically tailored total parenteral nutrition regimen. This, despite obviously impaired liver function, allowed adequate nutrition without the expected adverse metabolic sequelae associated with hepatic resection and nitrogen loading. The patient also demonstrated, in the absence of normal hepatic tissue, an ameliorated metabolic response to trauma. PMID- 3105056 TI - Human lymphocytes making rheumatoid factor and antibody to ssDNA belong to Leu-1+ B-cell subset. AB - B lymphocytes bearing the Leu-1 cell-surface antigen (Leu-1+), the human equivalent of mouse Ly-1+ B lymphocytes, have been detected in human peripheral blood, but there is little information on their frequency and properties. Analysis by fluorescence-activated cell sorter and double immunofluorescence showed that Leu-1+ B cells are consistently present in the peripheral blood and spleens of healthy subjects and constitute 17.0 +/- 5.0% (mean value +/- standard deviation) and 17.3 +/- 3.9%, respectively, of total B cells. When purified Leu 1+ and Leu-1- B lymphocytes were transformed into immunoglobulin-secreting cells by infection with Epstein-Barr virus and the culture fluids were tested for reactivity with self-antigens, at least two important autoantibodies, antibody to the Fc fragment of human immunoglobulin G (rheumatoid factor) and antibody to single-stranded DNA, were found to be made exclusively by Leu-1+ B cells. It is concluded that the Leu-1+ lymphocytes represent a major subset of the normal human B cell repertoire and include the B cells capable of making autoantibodies similar to those found in systemic lupus erythematosus and rheumatoid arthritis. PMID- 3105057 TI - Rheumatoid factor secretion from human Leu-1+ B cells. AB - A human B cell subpopulation identifiable by the expression of the cell surface antigen Leu-1 (CD5) is responsible for most of the immunoglobulin M rheumatoid factor secreted in vitro after the cells are stimulated with Staphylococcus aureus. The ability of B cells bearing the Leu-1 marker (Leu-1+) to secrete rheumatoid factor is present early in development and extends to adulthood, since Leu-1+ B cells from cord blood and from peripheral blood lymphocytes of both normal adults and patients with certain autoimmune conditions secrete rheumatoid factor in comparable amounts. The neonatal enrichment of Leu-1+ B cells, the presence of Leu-1+ B cells in increased frequencies in patients with autoimmune disease, and the involvement of Leu-1+ B cells in autoantibody secretion suggest both developmental and functional homologies between this human B cell subpopulation and the murine Ly-1 B cell subpopulation. PMID- 3105058 TI - Promotion of tubulin assembly by aluminum ion in vitro. AB - It has been proposed that aluminum ion is a contributing factor in a variety of neurological diseases. In many of these diseases, aberrations in the cytoskeleton have been noted. The effects of aluminum ion on the in vitro assembly of tubulin into microtubules has been examined by determining the association constants for the metal ion-guanosine triphosphate-tubulin ternary complex required for polymerization. The association constant for aluminum ion was approximately 10(7) times that of magnesium ion, the physiological mediator of microtubule assembly. In addition, aluminum ion at 4.0 X 10(-10) mole per liter competed effectively with magnesium ion for support of tubulin polymerization when magnesium ion falls below 1.0 millimole per liter. The microtubules produced by aluminum ion were indistinguishable from those produced by magnesium ion when viewed by electron microscopy, and they showed identical critical tubulin concentrations for assembly and sensitivities to cold-induced depolymerization. However, the rate of guanosine triphosphate hydrolysis and the sensitivity to calcium ion-induced depolymerization, critical regulatory processes of microtubules in vivo, were markedly lower for aluminum ion microtubules than for magnesium ion microtubules. PMID- 3105059 TI - OTA cites financial disaster of Alzheimer's. PMID- 3105060 TI - Common pathogenetic mechanism for three tumor types in bilateral acoustic neurofibromatosis. AB - Bilateral acoustic neurofibromatosis (BANF) is a genetic defect associated with multiple tumors of neural crest origin. Specific loss of alleles from chromosome 22 was detected with polymorphic DNA markers in two acoustic neuromas, two neurofibromas, and one meningioma from BANF patients. This indicates a common pathogenetic mechanism for all three tumor types. The two neurofibromas were among three taken from the same patient, and both showed loss of identical alleles demonstrating that the same chromosome suffered deletion in both tumors. The third neurofibroma from this patient showed no detectable loss of heterozygosity, which suggests the possibility of a more subtle mutational event that affects chromosome 22. In the two acoustic neuromas, only a portion of chromosome 22 was deleted, narrowing the possible chromosomal location of the gene that causes BANF to the region distal to the D22S9 locus in band 22q11. The identification of progressively smaller deletions on chromosome 22 in these tumor types may well provide a means to clone and characterize the defect. PMID- 3105061 TI - Role of the contact system in fibrinolysis. PMID- 3105063 TI - Arachidonic acid metabolites in the perinatal period--Part I. PMID- 3105062 TI - [Arthrography and arthroscopy in the diagnosis of meniscus injuries. A prospective blind study comparing their accuracy and economy]. PMID- 3105064 TI - Pathways of arachidonic acid metabolism with specific application to the fetus and mother. PMID- 3105065 TI - Purification and quantification of arachidonate metabolites: critical evaluation of methods and interpretation of results. PMID- 3105066 TI - The initiation of labor in women: regulation of phospholipid and arachidonic acid metabolism and of prostaglandin production. PMID- 3105067 TI - Activation of uterine smooth muscle contraction: implications for eicosanoid action and interactions. PMID- 3105069 TI - Inhibition of arachidonic acid metabolism in the perinatal period: pharmacology, clinical application, and potential adverse effects. PMID- 3105068 TI - Arachidonic acid metabolites and the regulation of placental and other vascular tone during pregnancy. AB - The eicosanoids are ubiquitous metabolites of arachidonic acid that possess an array of biological actions including marked vasoactivity. They are produced in significant quantities by the fetus, chorion, amnion, placenta, and maternal vascular tissues, and they have many important functions in the development and maintenance of normal vascular tone in human gestation. Imbalances in the production of certain eicosanoids may lead to failure of appropriate fetal growth and development, as well as to certain maternal vasoconstrictive disorders, such as preeclampsia. There is evidence that the eicosanoids have powerful vascular effects on both sides of the placental circulation, so it is likely that the control of blood flow in this vascular bed is largely dependent on eicosanoid metabolites. Current knowledge of production, regulation and physiologic actions of the lipoxygenase metabolites as they relate to pregnancy is in the embryonic stage of development. It will be necessary to learn more about the factors that regulate both eicosanoid production and action before a better understanding of the complexities involved in the control of the placental circulation will be achieved. PMID- 3105070 TI - Prostaglandins and the developing kidney. AB - Prostaglandins PGE2, PGD2, PGI2, and PGF2 alpha, as well as thromboxanes and leukotrienes, are synthesized by the fetal and neonatal kidney. The major prostaglandin, PGE2, PGD2, and PGI2, increase RBF, free water clearance, urine flow, and natriuresis. Alterations in the synthetic and catabolic activity of renal prostaglandins with advancing gestational and postnatal age occur along with concomitant alterations in RBF, GFR, and water and electrolyte excretion, suggesting that the prostaglandins play an important role in renal functional development. Indomethacin treatment may affect both fetal and neonatal renal function. Long-term maternal indomethacin treatment may decrease fetal urine output enough to alter amniotic fluid volume. Neonatal indomethacin therapy may cause transient dose-related renal dysfunction characterized by a decrease in urine output, but this renal dysfunction also depends in part on dosage, timing of therapy, and the cardiovascular and renal status of the infant prior to treatment. New areas of research interest include urinary prostaglandins as a marker for development of essential hypertension, and the possible interaction between antenatal steroids and renal function in the newborn. PMID- 3105071 TI - [Nursing care for respiratory patients undergoing diagnostic examinations]. PMID- 3105073 TI - [Humanization]. PMID- 3105072 TI - [What everyone should know about natural family planning]. PMID- 3105074 TI - [The stoma patient. A nursing challenge]. PMID- 3105075 TI - [Occupational health program for the workers of health centers]. PMID- 3105077 TI - [Integration of the teaching of nursing into the national education system. Its importance in the health development of Portugal]. PMID- 3105076 TI - [A method for trying to prevent in childhood the risk of obesity as an adult]. PMID- 3105078 TI - Evaluation of holistic medicine. AB - As an increasingly informed public becomes more and more disillusioned with the failure of scientific medicine to live up to its promises and to fulfill popular expectations, attention has been turning to 'holistic,' 'traditional,' 'alternative' or 'complementary' medicine. Forms of medical treatment such as acupuncture, homeopathy, and ayurvedic medicine have infrequently been rigorously evaluated. This paper reviews the traditional structures of clinical and economic evaluation of health care, and then describes a particular set of specific problems that would be encountered in applying these techniques to 'holistic' medicine under the headings 'reductionism' (bias from excluding certain categories of effects), 'taxonomic difficulties' (problems inherent in the choice of diagnostic criteria), and the 'logical basis for comparison' (procedural difficulties). Various methods for comparing the results of different schools of medical thought are suggested and evaluated. PMID- 3105079 TI - Coping with intestinal illness among the Kamba in Machakos, Kenya, and aspects of schistosomiasis control. AB - In a hyperendemic schistosomiasis mansoni area in Machakos District, Kenya, the Kamba use modern and traditional health services interchangeably with similar results. Schistosomiasis oral drug therapy administered through the Schistosomiasis Research Project reportedly achieved significantly higher cure rates than hospital and health center treatment, which in turn was not more effective than traditional medicine. Kamba knowledge and perceptions of the causes of intestinal illness, several types of preventive behavior, the role of women as health promotors, development of community water supplies and the utilization of plant molluscicides are briefly evaluated for possible use in the planned national schistosomiasis control program. PMID- 3105080 TI - [Bacteriology of tuberculosis]. PMID- 3105081 TI - [Antitubercular agents]. PMID- 3105082 TI - [Theoretical basis for the treatment of tuberculosis]. PMID- 3105083 TI - [Physiopathology of tuberculosis]. PMID- 3105084 TI - [Ergotamine tartrate]. PMID- 3105085 TI - Platelet satellitism: a possible mechanism. AB - Markedly increased platelet surface-bound IgG was found on platelets collected in citrate and heparin in a patient with platelet satellitism. The level on platelets collected in EDTA was mildly increased. However, neutrophils from this patient collected in EDTA had markedly increased surface IgG due to attached platelets, while no surface IgG was seen in citrate or heparin neutrophils, indicating that the anticoagulant EDTA in some way modified the surface IgG or neutrophil membrane resulting in platelet attachment. This is the first case in which a possible mechanism for platelet satellitism has been identified. PMID- 3105086 TI - Cold hemagglutinin disease in the operating room. AB - Cold hemagglutinin disease is infrequently recognized before complications ensue. We describe a patient with chronic cold hemagglutinin disease who sustained an acute hemolytic crisis during a routine operative procedure in a cool operating room. Cold agglutinins were present during routine preoperative blood cross matching with the Coombs' test positive for C3d. Analysis of the offending cold agglutinin revealed a high-titer monoclonal IgM-kappa antibody with anti-I specificity and broad thermal amplitude. Major complications from the presence of cold agglutinins have been poorly documented and are often thought to be of only theoretic concern. This case and literature review show that such complications may occur and emphasize the importance of careful preoperative plans when the Coombs' test suggests that cold agglutinins exist. PMID- 3105087 TI - Cost-effectiveness research in malaria control and the need for health behaviour and socio-economic research in malaria control in Thailand. AB - The complexity of the malaria situation in Thailand requires behavioural and socio-economic research in wide variety of areas including; migration, illness behaviour, motivation of staff and communities and the relationship of institutional and community expenditure to reduction in morbidity. The research ideally should be constructed in such a way as to maximize the availability of methods for incorporation into routine monitoring, evaluation, and policy making activities of the Anti-Malaria Programme. PMID- 3105088 TI - An economic perspective on the cost of disease. PMID- 3105089 TI - [Effect of nitroglycerin-retard on indices of plasma and platelet hemostasis]. PMID- 3105090 TI - [Ultrasonic aerosol treatment of open wounds of the extremities]. PMID- 3105091 TI - [Causes of disability after biliary tract surgery and ways of preventing it]. PMID- 3105092 TI - [Prediction of peripheral blood leukopenia during tumor chemotherapy]. PMID- 3105093 TI - [Evaluation of the effectiveness of artificial feeding of surgical patients]. PMID- 3105094 TI - Regional localization of carbonic anhydrase genes CA1 and CA3 on human chromosome 8. AB - The human carbonic anhydrase isozymes represent a family of homologous proteins which are important in respiratory function, fluid secretion, and maintenance of cellular acid-base homeostasis. Using somatic cell genetic techniques we have mapped two of the CA genes (CA1 and CA3) to human chromosome 8. In situ hybridization data demonstrates that both CA1 and CA3 map to the same region (q13 q22) of chromosome 8. PMID- 3105095 TI - Localization of UDP glucuronosyltransferase gene(s) on mouse chromosome 5. AB - The drug-metabolizing UDP glucuronosyltransferases are encoded by genes which constitute a multigene family. One rat gene subfamily codes for at least four constitutive enzyme forms, including those which glucuronidate the androgenic steroids testosterone (UDPGTr-3) and androsterone (UDPGTr-4). In the present study, UDPGTr-3 and UDPGTr-4 cDNAs were used to demonstrate that an homologous subfamily is present in the mouse genome. Using mouse X Chinese hamster somatic cell hybrids, we mapped at least one gene of this UDP glucuronosyltransferase subfamily (UDPGTr-3) to mouse chromosome 5 and suggest the name as the Udpgt-3 locus. PMID- 3105096 TI - [Variation in the right proper hepatic artery of importance to biliary tract surgery]. PMID- 3105097 TI - [Ovulation induction for in vitro fertilisation at the Tygerberg Hospital]. AB - The protocol for in vitro fertilisation (IVF) at Tygerberg Hospital is presented and the results are analysed. Indications for ovulation induction for IVF included the following: (a) irreversible tubal damage; (b) infertility due to immunological factors; (c) male factor-infertility; and (d) endometriosis. A combination of human menopausal gonadotrophin (HMG) and clomiphene citrate (Clomid; Mer-National) and human chorionic gonadotrophin was used. Clomid is given in dosages of 100 mg for 5 days depending on the cycle length. Three doses of HMG (150 IU) are given on alternate days, starting on the second day of clomiphene treatment. If the leading follicle has not reached a mean diameter of 14 mm the day after the last HMG dose, another dose is given. This dosage is continued until the leading follicle reaches a diameter of 14 mm. A total of 109 cycles in 100 patients was analysed. Ova were considered to be mature as soon as the dominant follicle had reached a sonographic average diameter of 18 mm, another two follicles of 16 mm average diameter being present. Serum luteinising hormone levels were determined 4-hourly from the stage when the leading follicles exceeded an average diameter of 14 mm. In this study the pregnancy rate was 21,3% per laparoscopy and 24,4% per embryo transfer. The oestradiol levels on the 5th day of treatment have a predictive value of the length of stimulation. PMID- 3105098 TI - The adult respiratory distress syndrome in association with diabetic keto acidosis. A case report. AB - A 41-year-old man presented in stupor, with ketoacidosis and acute severe respiratory failure. He had a history of alcohol abuse and had been on insulin therapy for diabetes secondary to chronic pancreatitis for 11 years. the condition was rapidly progressive and the patient died within 5 hours of presentation of profound hypoxia and hypotension despite aggressive therapy. Autopsy confirmed the clinical diagnosis of 'shock lung'. None of the more commonly associated precipitating factors of adult respiratory distress syndrome could be detected clinically or at autopsy and the pathogenesis of the condition remains elusive. PMID- 3105100 TI - [Results of curative high-voltage irradiation of prostatic cancer]. AB - The results of percutaneous irradiation of 111 patients with prostatic carcinomas during the years from 1974 through 1984 are retrospectively analyzed. A 8 MV X radiation was applied in form of a moving field therapy charging the prostatic bed with a dose of 67.5 Gy in the 90% isodose enclosing the tumor; the regional lymph nodes were exposed to a total dose of 40 to 50 Gy. CT irradiation planning was used since 1976. All patients showing metastases received endocrine treatment or a cytostatic therapy. The corrected probability of a 10 year survival is 88% for a collective of carcinomas mainly limited to the capsula. Local recurrences were found in 2.7% and local recurrences accompanied by formation of metastases in 5.4% of cases. 12% of the patients showed chronic radiogenic side effects. The influence exerted on the survival curves by tumor stage, histological grade as well as other prognostic factors is discussed. PMID- 3105099 TI - Epidemiology of gonorrhea: distribution and temporal changes in auxotype/serovar classes of Neisseria gonorrhoeae. AB - The auxotype/serovar (A/S) class of 489 isolates of Neisseria gonorrhoeae were determined and 425 isolates from 390 consecutive patients with gonorrhea who attended the Sexually Transmitted Diseases Clinic at Harborview Medical Center in Seattle during the first three months of 1985 were analyzed. Patients included 123 women, 187 heterosexual men, and 80 homosexual men. A total of 57 A/S classes of N. gonorrhoeae were identified during this study. For the first eight weeks, between three and seven new A/S classes were identified each week. The number of new A/S classes encountered in this community declined subsequently, and leveled off at about zero to two new A/S classes introduced per week. Two A/S classes were limited almost solely to homosexual men, one group of related classes was limited to heterosexual patients, and one class was initially limited largely to heterosexual men, possibly because of spread from a prostitute. The results show that the A/S classification system can be used in combination with epidemiologic data for tracing the introduction and spread of gonoccocal strains and their eventual elimination from a community. A/S classification can be used to study the clinical epidemiology of gonorrhea and may facilitate evaluation of strategies for control of gonorrhea. PMID- 3105101 TI - [Combination of bilateral pelvic lymphadenectomy, permanent iodine-125 implantation and percutaneous irradiation of localized prostate carcinoma. 1: Methods and results]. AB - Since the beginning of 1981, 32 patients at an age of 52 to 72 years who suffered from a locally confined adenocarcinoma of the prostate were treated by permanent implantation of iodine-125 seeds at the Urologic and Radiotherapeutic Hospital of the University of Erlangen. 25 patients were evaluated after a median observation period of 30 months. The first group consisting of 19 patients was submitted to a combined percutaneous and interstitial treatment, the other six patients were initially treated only by interstitial therapy because of severe complications observed in the meantime. After bilateral pelvic staging lymphadenectomy, permanent iodine-125 seeds were implanted into the patients of stage T1, T2, early T3, and pN0-1, in case of microscopic lymph node manifestation without capsular perforation also into patients of stage pN2 and pN4. Eight weeks later the patients received a moving beam irradiation with 10 MV photons at the linear accelerator. The centre of the prostate was faded out by a specially constructed H absorber in such a way that the prescribed target dose of 36 Gy in four weeks to the 90%-isodose was only applied to a spherical surface around the implant. One patient died perioperatively from an embolism due to phlebothrombosis of the thigh. 22 out of the other 24 patients are in complete remission, one patient had a local recurrence in the right seminal vesicle which appeared 28 months after primary therapy, and one patient developed skeletal metastases. The objective side effects and late complications of our combined treatment are considerable with respect to their incidence as well as their severity: a slight or medium radioproctitis was found after a latent period of one to two years in 28% (5/18) of cases, after a latent time of about 1 1/2 to two years another 28% (5/18) developed subsequently to a proctitis an urethral stricture and an ulcer situated on the anterior rectum wall facing the prostate, and four patients presented finally a prostato-rectal fistula. PMID- 3105102 TI - [Combination of bilateral pelvic lymphadenectomy, permanent iodine-125 implantation and percutaneous irradiation of localized prostate carcinoma. 2: Discussion and conclusions]. AB - Severe complications (urethral stricture, ulcer at the anterior rectum wall, prostato-rectal fistula) have been observed in 28%(5/18) of patients treated by combined percutaneous and interstitial therapy for locally confined prostatic cancer. These complications were caused above all by charging the big prostatic volumes with an excessive number of iodine-125 seeds applied through cannulas arranged too closely and by an insufficient distance between the mucous membrane of the rectum and the first seed. The evaluation of our data showed insignificant complications up to a total activity of 28 mCi, slight or medium complications between 28 and 35 mCi, and severe complications between 35 and 40 mCi. It is therefore necessary in case of an intended combination of interstitial and percutaneous irradiation to take precautionary measures already during the implantation in order to avoid critical accumulated doses: the spatial distribution of the seeds may be not so close and the total activity has to be lower (25 to 30 mCi). The MPD (minimal peripheral dose) can be by 30 to 40% below that of implantation alone and the dose in the centre of the implant should not exceed the MPD value by more than 100%. If a considerable volume (greater than 10 cm3) is irradiated by the implant with more than 240 Gy, the percutaneous boost generally performed up to 40 Gy has to be reduced, or the centre of the implant must be shielded by lead satellites after 20 Gy at the latest. The distance between the seeds and the mucous membrane of the rectum should be at least 1 cm, the interval between interstitial and percutaneous irradiation at least 8, better 12 weeks. A percutaneous boost is only performed in case of a very inhomogeneous interstitial dose distribution and a too low MPD (in form of a rotating irradiation up to 30 Gy: 16 Gy by open radiation and 14 Gy with H absorber) or in case of microscopic manifestations in the pelvic lymph nodes or suspected beginning manifestations in the seminal vesicles (in form of a four field irradiation up to 50 Gy using individual secondary collimators in order to shield sound tissues as well as the prostate which is already sufficiently irradiated by the seeds. PMID- 3105103 TI - Teratogenicity of di(2-ethylhexyl) phthalate, 2-ethylhexanol, 2-ethylhexanoic acid, and valproic acid, and potentiation by caffeine. AB - It is hypothesized that the teratogen di(2-ethylhexyl) phthalate (DEHP) acts by in vivo hydrolysis to 2-ethylhexanol (2-EHXO), which in turn is metabolized to 2 ethylhexanoic acid (2-EHXA), the proximate teratogen. Teratological studies were conducted with Wistar rats, with administration of these agents on day 12 of gestation. On an equimolar basis DEHP was least potent, 2-EHXO was intermediate, and 2-EXHA was the most potent of the three agents, which is consistent with the hypothesis. Similarity in the types of defects found with these agents also suggests a common mechanism, with 2-EHXA as the proximate teratogen. All three agents were potentiated by caffeine. Valproic acid, which is an isomer of 2-EXHA, also produced similar defects, and was approximately twice as potent as 2-EHXA. PMID- 3105104 TI - The effects of modulation of prostanoid metabolism on the thoracic platelet accumulation induced by intravenous administration of collagen in the guinea-pig. AB - The effects of intravenously administered collagen on the circulatory platelet count, TxB2, 6-keto PGF1 alpha and 51Cr-labelled platelet accumulation in the thorax have been evaluated in the guinea-pig. Administration of collagen induced a dose-related peripheral thrombocytopenia and a concomitant increase in 51Cr labelled platelets in the thorax. There was also a transient dose-related increase in plasma TxB2 but no change in plasma 6-keto PGF1 alpha levels. The thromboxane synthetase inhibitors tested, reduced the platelet accumulation, but only CGS 13080 significantly inhibited TxB2 production. In contrast all the cyclooxygenase inhibitors tested impaired the elevation of plasma TxB2 after collagen, but only diclofenac inhibited the 51Cr-labelled platelet accumulation. The greater effect of thromboxane synthetase inhibitors compared to cyclooxygenase inhibitors on platelet accumulation in this system cannot be completely explained by the changes measured in the circulating prostanoids. PMID- 3105105 TI - The interaction of the factor VIII/von Willebrand factor complex with hematin. AB - Intravenous infusion of hematin, used in the treatment of acute porphyria, induces a decline in the plasma factor VIII/von Willebrand factor complex (VIII/vWF) and thrombocytopenia. We investigated this problem by studying the interaction between hematin, purified VIII/vWF, and platelets in vitro. Hematin was labeled with either 59Fe or 3H and characterized by gel chromatography. Hematin self-aggregated, forming a complex with an average molecular weight of approximately 10,000 daltons. When incubated with VIII/vWF for 30 min at 37 degrees C and applied to Sepharose CL-4B, the hematin eluted with the VIII/vWF in the void volume. Hematin inhibited the dissociation of factor VIII antigen (VIII:Ag) from the von Willebrand antigen (vWF:Ag) in 0.25 M CaCl2, and reversed the aggregation of VIII:Ag induced by 0.1 M 6-aminocaproic acid. Both hematin and the hematin-VIII/vWF complex bound to washed normal platelets and to platelets from a patient with Bernard-Soulier syndrome. Thrombasthenic platelets were not aggregatable by hematin, and bound significantly less hematin-VIII/vWF than normal platelets suggesting that hematin-induced platelet activation was required for binding. Likewise, binding was inhibited by PGE1 which also prevented aggregation. We conclude that hematin forms complexes with VIII/vWF, alters the functional activity and dissociation of this compound, and participates in the binding of VIII/vWF to platelets. PMID- 3105106 TI - Bioavailability in rats of human recombinant tissue plasminogen activator after subcutaneous and intramuscular injection. AB - The bioavailability of human recombinant tissue plasminogen activator (rt-PA) in rats was measured after subcutaneous (s.c.) and intramuscular (i.m.) injection. Rt-PA was absorbed after both i.m. and s.c. injection, giving peak plasma concentrations within 30 min and 1 h, respectively, with detectable concentrations up to 6 h. These peak values of bioavailable t-PA were obtained in a functional fibrin plate assay of euglobulin precipitates and expressed as +88% and +243% (for s.c. and i.m. routes respectively) above basal rat fibrinolytic activity. Prior injection of rt-PA, s.c. or i.m., significantly reduced the weights of thrombi induced in the inferior vena cava after injection. PMID- 3105107 TI - Intrathoracic platelet accumulation in the guinea-pig induced by intravenous administration of arachidonic acid--effect of cyclooxygenase and thromboxane synthetase inhibitors. AB - Intravenous administration of arachidonic acid to guinea-pigs caused a dose related, rapid accumulation of 51Cr-labelled platelets in the thorax. Inhibitors of cyclooxygenase inhibited the platelet accumulation, induced by arachidonic acid (30 mg/kg), at doses which did not alter the thoracic blood volume (as measured by 131I-labelled human albumin). Thromboxane synthetase inhibitors had different effects on platelet accumulation depending on the dose. CGS 12970 (3 mg/kg) and N(1-carboxyheptyl) imidazole (100 mg/kg) reduced platelet accumulation. High doses of CGS 12970 and CGS 13080 caused an apparent enhancement of platelet accumulation which was associated with pooling of blood in the thorax, as measured by either 131I-labelled human albumin or 51Cr-labelled erythrocytes. This increase in thoracic blood volume was abolished if the guinea pigs were also pretreated with diclofenac (1 mg/kg) in addition to the thromboxane synthetase inhibitor. Increases in thoracic blood volume were also obtained following infusions of PGI2 but not PGD2 or PGE2. PMID- 3105108 TI - Further characterization of wheat germ agglutinin interaction with human platelets: exposure of fibrinogen receptors. AB - It was previously shown that Wheat germ agglutinin, (WGA)-induced platelet activation occurred when only 17% of the lectin binding sites were occupied on the platelet surface and WGA caused the release of a platelet constituent which in turn participates in the observed effect. We now further define the platelet activation induced by WGA: the lectin induces a binding of fibrinogen to specific surface receptors. 125I-fibrinogen binding increases with the WGA concentration from 5 to 15 micrograms/ml. Binding occurs without addition of exogenous calcium; its analysis demonstrated 54,000 sites with a Ka = 0.8 X 10(6) M-1. Addition of 1 mM Ca2+ enhances the 125I-fibrinogen binding and reveals a second class of sites with higher affinity (9200 sites, Ka = 0.17 X 10(8) M-1). This 125I-fibrinogen binding is totally abolished by EDTA, ATP and arginine, and inhibited by 75% by CP/CPK; cyclooxygenase inhibitors and PGE1 also reduce the fibrinogen binding. Thus the WGA-induced fibrinogen binding is release-dependent and responsible for the aggregation process but not for the agglutinating effect of the lectin. PMID- 3105109 TI - Factor VIII: C (FVIII: C) recovery and half-life after infusion of steam-treated high purity factor VIII concentrate in severe hemophilia A--comparison of one stage assay, two-stage assay and a chromogenic substrate assay. AB - Factor VIII:C recovery and half-life was measured in 16 hemophilia A patients under comprehensively standardized conditions. Each patient received the same lot of a steam-treated high purity FVIII concentrate at a dose of 19-33 U/kg body weight. A comparison was made between the one-stage assay, the two-stage assay and a chromogenic substrate test for FVIII:C determination using a FXa-sensitive chromogenic substrate. Factor VIII:C potency of the administered FVIII concentrate was measured using calibration curves derived from a concentrate standard and FVIII:C plasma levels were read from calibration curves derived from a plasma standard. The chromogenic assay showed a good reproducibility at FVIII:C levels between 0.015 and 0.50 U/ml. The FVIII:C recoveries calculated from the results of the one-stage assay, the two-stage assay and the chromogenic substrate test were 109 +/- 20, 92 +/- 14 and 81 +/- 11% (mean +/- SD), respectively. The elimination half-lives of FVIII:C were calculated by non-linear least square analysis using a modified computerized Gauss-Newton algorithm. The half-lives calculated from the FVIII:C plasma levels measured by the one-stage assay, the two-stage assay and the chromogenic test were 23.8 +/- 6.4, 22.2 +/- 5.7 and 17.1 +/- 4.8 h (mean +/- SD), respectively. No previous study has reported such long half-life values. Our findings indicate that measurements of recoveries and half lives by the chromogenic FVIII:C assay and by computerized non-linear least square analysis allow the possibility of individualized FVIII replacement therapy. PMID- 3105110 TI - Differential detection of single-chain and two-chain urokinase-type plasminogen activator by a new immunoadsorbent-amidolytic assay (IAA). AB - A new immunoadsorbent-amidolytic assay (IAA) for the specific differential detection of two-chain urokinase-type plasminogen activator (tcu-PA) and its single-chain precursor (scu-PA) in cell culture supernatants has been developed. The assay combines the selectivity of immunoassays with the specificity of enzyme activity assays exploiting both the antigenic and enzymatic properties of the two proteins. tcu-PA and scu-PA are selectively immunoadsorbed on the wells of a microtiterplate coated with the monoclonal antibody 5B4 and tested for enzymatic activity before and after activation by plasmin treatment. Both proteins are determined with similar efficiency since overlapping dose-response curves were obtained in the range between 12.5-200 ng/ml. The assay has been used to determine tcu-PA and scu-PA in A431 human epidermoid carcinoma cell supernatants. The analytical recoveries for tcu-PA and scu-PA added to A431 cell supernatants were 95.2% and 96.9% respectively. The intra- and inter-assay variations (CV) were 5.5% and 9.0% for tcu-PA and 9.7% and 9.8% for scu-PA respectively. PMID- 3105112 TI - Cyclooxygenase--independent pathway of phospholipase activation in carrageenan- induced platelet aggregation. AB - Carrageenan induced aggregation and ATP release of washed rabbit platelets. The aggregation was resistant to indomethacin or creatine phosphate/creatine phosphokinase system but sensitive to mepacrine or p-bromophenacyl bromide. Chlorpromazine, verapamil or tetracaine inhibited carrageenan-induced aggregation, ATP release reaction and membrane-bound calcium redistribution in washed platelets. Agents elevating cyclic nucleotides selectively inhibited the release reaction without affecting the aggregation. The mechanism of carrageenan mediated platelet responses may be due to both activation of phospholipases A2 and C. Platelet activating factor, protein kinase C and inositol triphosphate or phosphatidic acid could be mediated by carrageenan to accomplish the cyclooxygenase-independent events. PMID- 3105111 TI - Measurement of urokinase-type plasminogen activator (u-PA) with an enzyme-linked immunosorbent assay (ELISA) based on three murine monoclonal antibodies. AB - An enzyme-linked immunosorbent assay (ELISA) for the measurement of urokinase type plasminogen activator (u-PA) was developed. Three murine monoclonal antibodies to single chain urokinase-type plasminogen activator (scu-PA) were isolated and shown to react with non-overlapping epitopes in scu-PA. Two of the three antibodies were coated onto microtiter plates and bound u-PA was quantitated with the third antibody conjugated to horseradish peroxidase. The assay was equally sensitive to Mr 54,000 u-PA in the single chain or two-chain form but did not respond to Mr 33,000 urokinase. The lower limit of sensitivity of the assay was 0.1 ng/ml in buffer and 1 ng/ml in plasma. Coefficients of variation of the assay at physiological levels of u-PA were 6.5 percent within assays and 13 percent between assays. The level of u-PA in normal resting plasma was 1.9 +/- 0.66 ng/ml (mean +/- SD, n = 54). The assay can be performed within one working day and provides an efficient, reproducible, and stable means for the measurement of u-PA in biological fluids. As such it may facilitate physiological and pharmacological studies of urokinase-type plasminogen activators in man. PMID- 3105113 TI - A potential new procedure for removing anti-factor VIII antibodies from hemophilic plasma. AB - A new approach for removing the anti-factor VIII antibodies in hemophilic patients by immunoadsorption is proposed. The method is based on the fact that the anti-factor VIII antibodies were predominantly of the IgG4 subclass; anti human IgG4 antibodies were covalently linked to agarose and large amounts of anti factor VIII antibodies can be eliminated. A study of 21 blood samples from hemophilic patients with anti-factor VIII antibodies allows us to confirm the large predominance of IgG4 in the anti-factor VIII population. In some samples, the presence of IgG3 related anti-VIII:C was checked by adsorption on an anti IgG3 column. In a majority of cases, after IgG4 (or IgG4 + IgG3) immunoadsorption, the substitution therapy becomes possible or easier. PMID- 3105114 TI - von Willebrand factor antigen in urine. AB - Human urine was analyzed using a sensitive enzyme linked immunosorbent assay (ELISA) for von Willebrand factor (VWF) antigen. Urine of healthy persons contained VWF immunoreactivity. In the urine of a patient with severe von Willebrand disease, the VWF antigen was not detectable before but after intravenous infusion of von Willebrand factor-Factor VIII (VWF-FVIII) concentrate. The VWF antigen in normal urine was analyzed by gel permeation high performance liquid chromatography (HPLC). Three immunoreactive components of Mr 350 KDa, 60 KDa, and 20 KDa, respectively, were observed. Chromatography on concanavalin A-Sepharose revealed heterogeneity of the major 60 KDa component since only part of the material had affinity for the matrix. The 350 KDa material displayed affinity for Con A-Sepharose but not the 20 KDa. Gel electrophoresis combined with immunoblotting of normal urine gave similar results to those obtained by HPLC analysis. Immunoreactive components with apparent molecular weights similar to the largest urinary antigens were also observed in normal plasma but they were, nevertheless, not identical to the urinary antigens. PMID- 3105115 TI - Mechanism of vasopressin-induced platelet aggregation. AB - The mechanism of aggregation induced by arginine vasopressin (AVP) was studied in human platelet rich plasma. AVP--over the range of 1.8-113.6 mU/ml--caused a dose dependent aggregation with a concomitant stimulation of thromboxane B2 (TXB2) formation. d(CH2)5Tyr (Me)AVP did not by itself affect platelet aggregation or TXB2 release, but completely inhibited the action of AVP. DDAVP up to the concentration of 280 pM/ml had no effect on aggregation. Pretreatment of platelets with verapamil, trifluoroperazine or methylimidazole, a thromboxane synthetase blocker, prevented AVP-induced aggregation and TXB2 release. Neither phenidone in lower concentration nor nordihydroguaiaretic acid inhibited the ability of AVP to induce aggregation and TXB2 release. These results are consistent with the hypothesis that human platelets possess AVP receptor of the calcium-dependent vasopressor (V1) subtype and suggest that AVP-induced platelet aggregation is mediated via thromboxane release. PMID- 3105116 TI - Antithrombin antigen of high molecular weight associated with neoantigen in hemophilic plasma after factor IX concentrate therapy. AB - These studies were performed to investigate the cause(s) of the cathodal shift of mobility seen in crossed immunoelectrophoresis of antithrombin antigen in plasma of hemophilic patients after factor IX concentrate therapy. These plasmas were shown to contain antithrombin neoantigen with apparent identity to the neoantigen present in normal serum but not present in normal plasma. Sephacryl S-200 gel chromatography of serum demonstrated that the neoantigen eluted with the first two, early eluting protein peaks; thus the neoantigen had a higher molecular weight than native antithrombin. When the chromatographic fractions containing the neoantigen were studied by crossed immunoelectrophoresis, they were found to contain antithrombin antigen of more cathodal mobility than normal. Sephacryl S 200 chromatography of factor IX concentrate-treated hemophilic plasma also showed an early eluting peak of antithrombin antigen of more cathodal mobility than normal in crossed immunoelectrophoresis. The mobility of this peak was identical to the cathodal peak found in normal serum and in early eluting fractions from chromatography of normal serum. These results support the conclusion that factor IX concentrate-treated hemophilic plasma contained a non-functional, high molecular weight form of antithrombin, associated with the presence of neoantigen, which may represent complexed and/or modified antithrombin produced by the action of the concentrates in vivo. PMID- 3105117 TI - Antitumor activity of lipopolysaccharide in tumor-bearing mice pretreated with BCG. AB - The antitumor activity of lipopolysaccharide (LPS) was investigated in BCG treated mice. C3H/He mice and CDF1 mice were injected with BCG and then were inoculated with syngeneic mouse hepatoma MH134 and mastocytoma P815 respectively. Hemorrhagic necrosis and retarded growth of tumor were observed after an intravenous (i.v.) injection of LPS, when tumor cells had been inoculated subcutaneously (s.c.). However an intraperitoneal (i.p.) injection of BCG plus LPS did not increase the mean survival time of mice that had been inoculated with tumor cells i.p. Sera from mice that had been treated with BCG plus LPS i.v. were cytotoxic for cultured tumor cells. These results seemed to indicate that growth inhibitory effects of LPS on tumors inoculated s.c. were mediated by a humoral factor. PMID- 3105118 TI - Alternative delivery systems and employers. PMID- 3105119 TI - Binding of [14C] allylamine to isolated mitochondria from rat heart and aorta. AB - This study demonstrates specific and saturable binding of [14C] allylamine to mitochondria derived from rat aorta and heart. Specific binding is linear with respect to mitochondrial concentration and has a pH optimum of 7.0. Saturation isotherms reveal anomalous kinetics of specific binding on heart mitochondria with a high affinity site (KD 16 nM) and a lower affinity site (KD 80 nM); Scatchard plots have a common intercept. Exhaustive flow dialysis in the presence of SDS demonstrates that as much as 23.5% of bound radioactive moieties in aorta mitochondria are covalently bound, and as much as 42.6% are covalently bound in heart mitochondria. Hydrolysis of heart mitochondria with phospholipase C markedly enhances saturation of [14C] allylamine, and greatly increases the quantity of covalently bound radioactive ligand. Phospholipase C hydrolysis of heart mitochondria increased monoamine oxidase B activities and unmasked a small amount of benzylamine oxidase activity, whereas hydrolysis of mitochondria with phospholipases A2 and D diminish MAO-B activity. The monoamine oxidase B inhibitor, deprenyl, significantly reduced both specific and covalent binding of the 14C-activity from [14C] allylamine to phospholipase hydrolyzed mitochondria. The benzylamine oxidase inhibitor, phenelzine, significantly decreased specific binding but had no effect on the degree of covalent binding of [14C] allylamine to phospholipase C hydrolyzed mitochondria. The benzylamine oxidase inhibitor, semicarbazide, had no effect in inhibiting [14C] allylamine binding. Covalent binding of 14C-moiety from [14C] allylamine to mitochondria--which express specific binding sites for the [14C] allylamine--and inhibition of binding by monoamine oxidase inhibitors, suggest the formation of highly reactive intermediates. PMID- 3105120 TI - Iodoacetic acid and related sulfhydryl reagents fail to inhibit cell-cell communication: mechanisms of immunotoxicity in vitro. AB - The present study was undertaken to examine the effects of iodoacetic acid, a non phorbol tumor promoter, on metabolic cooperation between mutant human fibroblasts as measured by [14C]citrulline incorporation. Other thiol-reactive polyphenolic compounds such as hydroquinone and 2-hydroxyestrone were also examined. 12-O Tetradecanoyl phorbol-13-acetate (TPA), a potent skin tumor promoter, inhibited the cell-cell communication by more than 60% at 20 ng/ml. However, iodoacetic acid, hydroquinone, and 2-hydroxyestrone, had no effect on the process even at cytotoxic concentrations. Induction of intercellular contact (agglutination) among lymphocytes during the course of phytohemagglutinin (PHA)-induced blastogenesis was monitored turbidometrically at 620 nm. Hydroquinone and 2 hydroxyestrone suppressed the PHA-induced lymphocyte agglutination at 1-2 microM in vitro concentrations while iodoacetic acid was devoid of any effects at concentrations up to 100 microM. Hydroquinone and 2-hydroxyestrone concomitantly suppressed PHA-induced lymphocyte blastogenesis at 1-2 microM in vitro concentrations while the suppression by iodoacetic acid was significant at 10 microM. All 3 compounds failed to disrupt microtubule assembly, a sulfhydryl dependent process, in a rat brain crude extract. However, p-benzoquinone, an oxidation product of hydroquinone, did inhibit the process at 1 mM. In summary, these studies suggest that, unlike TPA, thiol-reactive non-phorbol tumor promoters and polyphenolic compounds do not inhibit cell-cell communication between mutant human fibroblasts. Although the compounds demonstrate diverse molecular mechanisms of action, they all inhibit in vitro immune functions suggesting that immunosuppression may play a role in tumor promotion. PMID- 3105121 TI - Purification and characterization of cytotoxic factors in the venom of the Okinawa habu (Trimeresurus flavoviridis). AB - Two cytotoxic factors in the venom of Okinawa habu (Trimeresurus flavoviridis), a crotalid, have been purified and characterized. They had cell monolayer disrupting activity against cells cultivated in vitro, but no proteolytic, hemorrhagic or direct hemolytic activity nor lethal toxicity. They were heat labile acidic proteins (isoelectric points 5.2 and 5.4) having similar molecular weights (approx. 14,000) and amino acid compositions. They were indistinguishable immunologically. PMID- 3105123 TI - The impact of DRGS on the OR. PMID- 3105122 TI - Cardiotoxicity of Naja nigricollis phospholipase A2 is not due to alterations in prostaglandin synthesis. AB - The basic phospholipase A2 from Naja nigricollis snake venom is cardiotoxic, causing decreased contractility and arrhythmias at concentrations which induce low levels of phospholipid hydrolysis. Cardiac tissue has a high content of arachidonic acid at the sn-2 position of the major membrane phospholipids, thus increased prostaglandin synthesis might contribute to the cardiotoxic effects of N. nigricollis phospholipase A2. Intracellular action potentials and cardiac contractility were monitored in the isolated right ventricular wall of the rat heart exposed for 1 hr to N. nigricollis phospholipase A2, with or without indomethacin, or to arachidonic acid. The tissues were homogenized, prostaglandins extracted and the 6-keto PGF1 alpha and PGE2 content of the hearts determined. The physiologic effects and prostaglandin content of hearts treated with N. nigricollis phospholipase A2 were not altered by indomethacin nor mimicked by concentrations of arachidonic acid comparable to that present in N. nigricollis phospholipase A2-treated tissue. These results support our previous suggestion that exogenously applied N. nigricollis phospholipase A2 causes cardiotoxic effects by a mechanism that is independent of phospholipid hydrolysis. PMID- 3105124 TI - Effect of immunosuppressives on gamma-interferon production, lymphocyte proliferation, and cytotoxic function of activated T lymphocytes. PMID- 3105125 TI - Both class I and class II responsive T cell subsets can separately initiate lethal graft-versus-host disease in H-2-incompatible murine radiation chimeras. PMID- 3105126 TI - T4+ cells can initiate human graft-versus-host disease. PMID- 3105127 TI - Murine cardiac allograft survival following treatment of recipients with monoclonal anti-L3T4 or Ly-2 antibodies. PMID- 3105128 TI - The effect of islet transplantation on diabetic retinal endothelial cell proliferation. PMID- 3105129 TI - The effect of chronic diabetes and continuous pretransplantation insulin infusion on the function of organ-cultured fetal islet isografts. PMID- 3105130 TI - The effect of murine fetal islet transplants on renal and retinal capillary basement membrane thickness. PMID- 3105131 TI - Transplanted fetal pancreas allografts regulate blood glucose to donor-strain levels. PMID- 3105132 TI - Rat fetal pancreas allograft survival is enhanced following donor tissue organ culture and host immunosuppression. PMID- 3105133 TI - Therapeutic use of the monoclonal antibody Orthoclone OKT3. PMID- 3105134 TI - Overview of the development of Orthoclone OKT3: monoclonal antibody for therapeutic use in transplantation. PMID- 3105135 TI - Immunologic monitoring of Orthoclone OKT3-treated patients: the problem of antimonoclonal immune response. PMID- 3105136 TI - A U.S. clinical study of Orthoclone OKT3 in renal transplantation. PMID- 3105137 TI - Use of Orthoclone OKT3 monoclonal antibody to reverse acute renal allograft rejection unresponsive to treatment with conventional immunosuppressive regimens. PMID- 3105138 TI - Orthoclone OKT3 treatment of acute renal allograft rejection in patients receiving maintenance cyclosporine therapy. PMID- 3105139 TI - Impact of Orthoclone OKT3 on liver transplantation. PMID- 3105140 TI - Use of Orthoclone OKT3 monoclonal antibody in cardiac transplantation: early experience with rejection prophylaxis and treatment of refractory rejection. PMID- 3105141 TI - Orthoclone OKT3 monoclonal antibody reversal of hepatic and cardiac allograft rejection unresponsive to conventional immunosuppressive treatments. PMID- 3105142 TI - Clinical development of Orthoclone OKT3. PMID- 3105143 TI - Renal failure in children of tropical West Africa. PMID- 3105144 TI - Orthoclone OKT3 treatment of acute renal allograft rejection. PMID- 3105145 TI - Nutrition in the management of renal failure in black children. PMID- 3105146 TI - [Light optical and electron microscopy research on the cyst-forming coccidium Sarcocystis muris]. AB - Part of the complicated life cycle of Sarcocystis muris, confined to the muscle cyst (sarcocyst), has been studied by light and electron microscopy. The early development of the sarcocyst proceeds strictly intracellularly, whereas the older and larger cysts tend to destroy the harbouring muscle cell, and since then their development seems to be intercellular rather than intracellular. Three different cell types are distinguished within the growing sarcocyst of S. muris differing from each other both structurally and functionally: metrocytes, intermediate cells and merozoites. These differ as well in the structure of their nuclei. The metrocyte nuclear chromatin is mainly in decondensed state with some minute granules taking the central part of the nucleus. The condensed chromatin of the intermediate cell is accumulated into some relatively large peripheral granules, whereas numerous RNP-granules appear in the karyolymph. The nuclear chromatin of merozoites is condensed to be seen as separate chromocenters scattered over the nucleus; the karyolymph is packed with RNP-granules. Metrocytes are seen to divide in young sarcocysts, although the mode of their division is still obscure. In sarcocysts of advanced age (2.5 months or more), only intermediate cells are seen to divide, their mode of division being endodyogeny. PMID- 3105147 TI - [Imipenem: correlation between agar diffusion tests and agar dilution tests]. PMID- 3105148 TI - [Comparative characteristics of the excretion of the nitrogenous components of phospholipids in diseases of the kidneys with secondary oxaluria in children]. PMID- 3105149 TI - Clinical use of carbon dioxide (CO2) laser in microsurgical vasovasostomy. AB - Herein are reported the first 4 clinical cases of carbon dioxide (CO2) laser microsurgical vasovasostomy. Fusion-coagulation of the vas wall was successfully accomplished, as demonstrated by adequate postoperative sperm counts and a 50 per cent pregnancy rate. A significant reduction in the total operative time was achieved as compared with the conventional microsurgical suture technique, corroborating the ability of the CO2 laser to simplify this technique while producing a sperm-tight anastomosis. PMID- 3105150 TI - Urethral diverticulum in females. PMID- 3105151 TI - [The effect of repeated administration of Oestrophan (SPOFA) on the quality of sexual function in breeding stock]. AB - The objective of the study was to check a contingent negative effect of repeated treatment of heifers by PGF2 alpha--Oestrophan (SPOFA)--on the course and quality of their ovarian activity and external heat signs. Changes in progesterone concentrations were evaluated three times a week. Three heifers were subjected to treatment eight times and two heifers nine times. Of 42 applications of Oestrophan (SPOFA) the response was positive in 95.2% (forty heats). When Oestrophan (SPOFA) was administered on the fourth and sixth day of the sexual cycle, in two cases no heat nor luteolysis of corpus luteum was detected; this was demonstrated by hormonal investigation. Of the forty evaluated heats, 82.5% were classified as strongly and medium expressive, the remaining were weakly expressive. The onset of heat was found to be on the average 72.6 hours after Oestrophan (SPOFA) administration, in 9.1% of the cases the heat started about 48 hours after administration, 12.4% of cows showed the heat signs between 72nd and 96th hours. PMID- 3105152 TI - [Chemical study of body organs in papular dermatitis in fattened pigs]. AB - In twenty fattened pigs with papular dermatitis (PD) and in seventeen pigs with no skin lesions (K),--the pigs had the live weight from 95 to 105 kg and came from a D. large fattening house situated in a region with extensive mining (lignite extraction)--we analyzed the skin, muscle, kidneys and liver for the contents of chemical elements (zinc, copper, manganese, lead, cadmium, mercury, chromium) and aflatoxin B1. In pancreas we analyzed only the content of aflatoxin B1. In comparison with the K group, the pigs with PD had in the skin the higher contents of zinc (PD 15.7 +/- 7.1 mg per kg, K 10.1 +/- 1.3 mg per kg, P less than 0.05) and aflatoxin B1 (PD 3.18 +/- 1.53 micrograms per kg, K 1.56 +/- 0.49 microgram per kg, P less than 0.05); in the muscle the higher contents of zinc (PD 30.2 +/- 7.6 mg per kg, K 23.8 +/- 5.4 mg per kg, P less than 0.05), of lead (PD 0.48 +/- 0.31 mg per kg, K 0.25 +/- 0.28 mg per kg, P less than 0.05) and copper (PD 3.19 +/- 3.11 mg per kg, K 0.98 +/- 0.41 mg per kg, P less than 0.01); in the kidneys the higher contents of lead (PD 0.96 +/- 0.75 mg per kg, K 0.26 +/ 0.34 mg per kg, P less than 0.01), cadmium (PD 0.38 +/- 0.14 mg per kg, K 0.26 +/- 0.20 mg per kg, P less than 0.05), manganese (PD 1.14 +/- 0.04 mg per kg, K 0.94 +/- 0.42 mg per kg, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105153 TI - [Dynamics of the incidence of coccidiosis in chickens in relation to the level of anticoccidial care]. AB - The incidence of coccidiosis was evaluated in pullets and broilers raised in large--scale conditions. We confirmed a relationship between the extensity and intensity of coccidium incidence on the one hand and the content of anticoccidic drugs in feed mixtures and the husbandry standard on poultry farms on the other. We studied the causes of failure of the efficiency of the anticoccidic drug Amprol Plus after a short time of its administration to the fowl and we demonstrated a resistant strain of the field isolate of Eimeria tenella in connection with low doses of this anticoccidic drug in feed mixtures. PMID- 3105155 TI - [The character of chromosome banding in the karyotype of the roebuck]. AB - We examined the karyotype in five individuals of roe-deer (Capreolus capreolus), coming from Southern Moravia. We subjected to examination the cells of bone marrow, lymphocytes of peripheral blood and germ sexual cells of roebuck. In all examined animals and in all examined tissues we found out a diploid number of seventy chromosomes. All autosomes were acrocentric, sex chromosomes had two arms. During the C-banding the centromere regions of all autosomes stained deep- dark; this demonstrated a great amount of constitutive heterochromatin. Chromosome X stained negatively during the C-banding. The pattern of G-banding was used to establish homologous pairs of chromosomes. PMID- 3105154 TI - [Effect of Sulfakombin SPOFA on the dynamics of the extent of coccidiosis in small rabbit breeding operations]. AB - We determined the yearly changes in coccidiosis extensity applying the results of an examination of 2707 rabbits performed in the years 1981-1984. A field trial was conducted to study the efficiency of the Czechoslovak anticoccidic drug Sulfakombin Spofa administered to control coccidiosis in small rabbit breedings. We made the calculations to find out the optimum time of administration of sulphonamide substances. We discuss certain factors that influence in a decisive way the changes in coccidiosis extensity in rabbit breedings. PMID- 3105156 TI - [Histologic and histochemical study of placentomes in cows after induced labor]. AB - The placentomes were extirpated from 16 cows after parturition induced with 750 micrograms cloprostenol or 20 mg dexamethasone on the 277th day of gravidity, on an average, from 9 cows after spontaneous parturition, and from 7 cows after hysterectomy in the eighth month of gravidity. In the cows with induced calving the foetal placenta was not expelled within 12 hours after calving in 68.7% of the cases whereas in the spontaneous parturitions this proportion was only 22.2% of cases. The placentomes obtained immediately after calf expulsion, and then after four and eight hours, were subjected to histological and histochemical examination. In the terminal crypts of the placentome in cross sections obtained from cows which expelled the placenta in time after natural and induced parturitions, the number of binuclear cells of the fetal syncytium and of cells of the dam epithelium (P less than 0.001) was found to be significantly lower than in the cases of afterbirth retention (1.2 and 3.9; 6.4 and 18.5). The cells of the cow's epithelium of the expelled placentae had a higher activity of acid phosphatase and lipids and the foetal syncytium had a higher activity of non specific esterase. Increased alkaline phosphatase activity was characteristic of the cow's epithelium in the cases of subsequent retention of afterbirth. These findings should be taken into account in efforts for developing new methods of the induction of parturition if the undesired occurrence of afterbirth retention is to be reduced. PMID- 3105157 TI - Invasion and intracellular development of Theileria annulata sporozoites in lymphoblastoid cell lines already transformed by T. annulata (Hissar), T. annulata (Ankara) and T. parva (Muguga). AB - Interactions between Theileria annulata sporozoites and lymphoblastoid cell lines already transformed by the Hissar and Ankara strains of T. annulata [T. a. (H) and T.A. (A), respectively] and the Muguga strain of T. parva [T.P. (M)] were studied in vitro. Although sporozoites of the Hissar strain of T. annulata attached to and entered peripheral blood lymphocytes (PBL) and lymphoblastoid cell lines transformed by T. a. (H) and T. a. (A), they neither attached to nor entered the T. p. (M) cell line. Whether the superinfecting T. a. (H) sporozoites developed intracellularly was studied by monitoring daily changes of mean schizont nuclear numbers and by determining electrophoretic mobilities of schizont glucose phosphate isomerase in each cell line using thin-layer starch gel electrophoresis. While the mean schizont nuclear number in freshly-infected PBL underwent a steady increase to the level of those in long standing T. annulata cultures, analysis of variance of similar data in T. a. (H) and T. a. (A) cell lines in which superinfection was demonstrated revealed no significant differences between them and their respective control counterparts, i.e., T. a. (H) and T. a. (A) cultures with no superinfection. Enzyme polymorphism studies showed the formation of uncontaminated species- or strain-specific bands of glucose phosphate isomerase (GPI) isoenzyme activity in the T. p. (M) and in the superinfected T. annulata cell lines. PMID- 3105158 TI - The effect of sarcoptic mange on growth performance, leukocytes and lymphocyte proliferative responses in pigs. AB - The effects of a single artificial infestation with sarcoptic mite (Sarcoptes scabiei var. suis DeGeer) on weight gain and lymphocyte blastogenic responses were studied in untreated and fenvalerate-treated pigs. Average daily feed intake, average daily gain and feed efficiency were monitored for 5 weeks in 32 infested and 16 uninfested pigs. Total and differential leukocyte counts were determined and lymphocyte proliferative responses, using a mitogen-stimulated lymphocyte blastogenesis assay, were evaluated in 24 pigs. Sarcoptic mite infestation or treatment for sarcoptic mange did not affect total or differential leukocyte counts (P greater than 0.10). Differences were not observed in weight gain or lymphocyte blastogenic responses between infested and uninfested pigs. PMID- 3105159 TI - Elimination of the gametocytes of Theileria annulata of cattle by primaquin phosphate. AB - Calves were experimentally infected with Theileria annulata and five drugs were administered in an attempt to exterminate the gametocytes of the parasite. The results of the experiment proved that primaquin phosphate is an effective parasiticide. The gametocytes from 30 calves treated with primaquin phosphate were exterminated completely. A further eight calves were treated with sulfamethoxypyrazine, trimethoprim, naganin and acaprin, but these drugs were not found to be effective in eliminating the gametocytes. The phase, size and colour of the gametocytes in these calves were the same as those of the four untreated control calves. PMID- 3105160 TI - Immunization against East Coast fever: the use of selected stocks of Theileria parva for immunization of cattle exposed to field challenge. AB - Two antigenically different stocks of Theileria parva parva (Kilifi and Marikebuni), previously characterized as belonging to groups A and C respectively on monoclonal antibody (MAb) profiles, were selected for immunization of different breeds of cattle against East Coast fever (ECF) by the infection and treatment method. A total of 52 immunized cattle and 33 susceptible controls of different group sizes were exposed to field challenge by ticks for periods of 42 90 days at three field sites where ECF is endemic on the Kenyan coast. All immunized cattle survived ECF challenge, but 87% of the controls died of the disease. The cattle exposed at one site had been immunized 1 year earlier and maintained tick-free in the intervening period. The level of immunity in these cattle was similar to that of cattle which had been immunized 1 or 2 months prior to exposure. Thus, immunity had not waned over the 1-year period. A study at another site showed that acaricidal treatment of immunized cattle could be safely extended from twice a week to once every three weeks, whereas in susceptible cattle even twice weekly spraying did not control ECF. The isolates made from infected controls during the trials indicated the presence of three T. p. parva stocks as defined by MAb profiles. Of the two stocks used for immunization, T. p. parva Marikebuni induced broader protection. In view of the apparent limited antigenic diversity of T. p. parva strains within the Coast Province it is suggested that the Marikebuni stock might represent a key stock for vaccination in this area. PMID- 3105161 TI - Relative importance of larval and adult Mecistocirrus digitatus in inducing resistance to a reinfection in calves. AB - Calves immunized with adult Mecistocirrus digitatus implanted directly into the abomasum did not develop a substantial degree of immunity to a subsequent large oral (challenge) dose of larvae, which developed to maturity. In contrast animals immunized by oral infection developed strong resistance. The calves implanted with adult worms appeared to show a greater degree of susceptibility to maturation of the challenge infection than controls which received a challenge of the same magnitude without any previous immunization. The implanted female adult worms established in the hosts and continued to produce more eggs for a longer time than those which developed to maturity from the oral immunizing infection with third-stage larvae. Passive haemagglutination studies revealed that the implanted adult worms stimulated little or no antibody response in the hosts. In the calves which did not show a response to the adult worm implant the subsequent challenge with an oral infective dose of third-stage larvae also failed to stimulate a response. Likewise the two calves from the group which showed a weak antibody response to the adult worm implant did not show an increased response when challenged. In contrast, calves immunized with an oral infection of third stage larvae had an antibody response which showed a vigorous rise on challenge in four of the five calves. Thus a direct relationship between resistance to challenge infection and the antibody response determined by the passive haemagglutination and gel-diffusion tests was observed in the calves immunized orally. PMID- 3105162 TI - Field evaluation of parvaquone against naturally occurring East Coast fever. AB - Parvaquone (Clexon Cooper) was clinically tested for efficacy as a treatment for East Coast Fever (Theileria parva parva infection) in naturally infected cattle. The drug showed a suppressive effect on Theileria schizonts and piroplasms. A recovery rate of 79% was recorded. Best results were obtained when Clexon treatment was initiated in the early stage of the disease, before many red blood cells were invaded and before respiratory distress was evident. A carrier state in animals recovered from East Coast Fever is suspected. PMID- 3105163 TI - Cultivation of Besnoitia besnoiti and evaluation of susceptibility of laboratory animals to cultured parasites. AB - Cultivation of Besnoitia besnoiti on five mammalian cell types showed that Vero (green monkey kidney), L929 (mouse fibroblasts) and BEK (bovine embryo kidney) cells were highly susceptible and were almost destroyed after 5 days of incubation, while MDBK (Madin-Darby bovine kidney) and BL (Theileria annulata infected bovine lymphoid) cells were less affected. Intraperitoneal infection with culture-derived endozoites was fatal for gerbils (Meriones tristrami) and sand rats (Psammomys obesus). Rabbits showed fever, conjunctivitis and orchitis, but survived the infection. Mice, rats, guinea pigs, hamsters and Microtus guentheri did not show signs of illness, but developed specific antibodies to B. besnoiti. B. besnoiti subcultivated for 2 years in BL cells remained virulent for gerbils. PMID- 3105164 TI - Ultrastructure of Sarcocystis spp. from donkeys (Equus asinus) in Egypt. AB - The fine structure of Sarcocystis spp. from donkeys (Equus asinus) in Egypt is described. Sarcocysts were found in the oesophagus, diaphragm and heart of 18 of 20 donkeys. Only one type of mature muscle cyst was found. Sarcocysts were 120 410.6 X 48.4-50.2 microns. The primary cyst wall had numerous 3.3-3.7 microns villi. Each villus contained 20-60 fibrillar elements which extended from the ends and sides of the villi throughout the ground substance, where they became tightly packed. The bundles of fibrillar elements formed junctions with the pellicles of the metrocytes. Ultrastructurally, Sarcocystis spp. of the donkey was similar to sarcocysts previously described from the horse. PMID- 3105165 TI - Hepar lobatum carcinomatosum due to metastatic breast carcinoma. AB - This is the first clinico-pathological report of hepar lobatum carcinomatosum (HLC), the rarest form of metastatic liver disease. The primary lesion was a scirrhous breast carcinoma. HLC closely resembles its syphilitic counterpart macroscopically, and is characterized by multifocal cancer-bearing scars and compensatory hyperplasia of the spared liver parenchyma. Multifocal carcinomatous obstruction of portal and hepatic venous vessels as well as rather slow progression of the clinical course may determine the development of HLC. In addition to the possible association of portal hypertension, the differential diagnosis from other types of unusual liver metastasis is discussed. PMID- 3105166 TI - Glycoconjugates in retinoblastoma. A lectin histochemical study of ten formalin fixed and paraffin-embedded tumours. AB - The binding of eleven biotin- or peroxidase-coupled lectins with different carbohydrate specificities to tumour tissue and remaining morphologically normal retina was studied in ten formalin-fixed and paraffin-embedded human eyes with retinoblastoma. In undetached retinas, outer and inner segments of photoreceptors bound concanavalin A (ConA) as well as Lens culinaris (LCA), wheat germ (WGA) Ricinus communis (RCAI) and peanut (PNA) agglutinins. Both nuclear and plexiform layers bound ConA, LCA and, in some specimens, WGA and RCAI. These results agree with those obtained with normal adult human retina, the main difference being that PNA labelled some rods in addition to cones in the retinoblastoma eyes. Flexner-Wintersteiner rosettes reacted with ConA and LCA, and often with WGA, PNA and RCAI. Undifferentiated retino-blastoma cells always bound ConA and LCA, and in some tumours WGA, PNA and RCAI. Pretreatment with neuraminidase increased the number of cells that bound PNA and RCAI, but diminished binding of WGA. Pokeweed mitogen and Bandeiraea simplicifolia I, Dolichos biflorus, soybean, Ulex europaeus I and Lotus tetragonolobus agglutinins labelled only vascular endothelial cells. Retinoblastoma cells most closely resembled photoreceptor cells in their lectin-binding patterns. PMID- 3105167 TI - Immunohistological characterization of a monoclonal antibody (OV632) against epithelial ovarian carcinomas. AB - A hybridoma cell line (OV632) producing monoclonal antibody against ovarian carcinomas was developed from the spleen cells of a mouse immunized with cystic fluid from a serous cystadenocarcinoma. Immunohistological studies in frozen sections showed that 22 out of 28 nonmucinous ovarian carcinomas, which included serous, endometrioid, clear cell, and undifferentiated tumours, reacted with this antibody. Three out of 7 mucinous ovarian carcinomas were positive, whereas only 7 out of 122 extra-genital malignant lesions, predominantly adenocarcinomas, were positive. The negative cases included 38 breast carcinomas and 24 colon carcinomas, tumours which are responsible for most of metastatic disease in the ovary. On the basis of these findings, the antibody OV632 is considered appropriate for histodiagnostic purposes as an aid in the distinction between primary and secondary ovarian cancer. PMID- 3105168 TI - Maintenance of normal human breast organoids within rat mammary fat pads in organ culture. AB - Normal human breast organoids, derived by collagenase digestion of reduction mammaplasty tissue specimens, have been cultured in vitro for up to 28 days after injection into organ cultures of virgin rat mammary fat pads. The culture medium was serum-free Waymouth's MB 752/1 with hormonal additives. The rat mammary tissue responded well to growth-promoting and lactogenic stimuli in the culture medium, in agreement with previous investigations. Using immunohistochemistry casein was identified in rat epithelia exposed to lactogenic medium. Human organoids in culture remained viable but did not show hormone-responsiveness. Electron microscopy confirmed the presence of both luminal epithelial cells and myoepithelial cells. The serum-free culture of normal human breast organoids in a three-dimensional matrix provides a system in which to study factors controlling growth and differentiation. PMID- 3105169 TI - Removal of cellular debris formed in the Disse space in patients with cholestasis. AB - Using electron microscopy, we investigated how cellular debris, formed in the Disse space during cholestasis, was cleared. Ten patients with cholestasis of varied origin and severity were studied and compared with 10 controls without liver disease. In cholestatic patients, sinusoidal cells contained variable amounts of amylase PAS-positive material. In clean perfusion-fixed sinusoids the endothelial cells often appeared swollen and active, with few fenestrations. Hepatocyte blebs and cellular debris were sometimes seen in the Disse space. Two mechanisms were apparently involved in the clearing process: phagocytosis by macrophages either infiltrated into the Disse space, or forming the barrier; and the passage of debris from the Disse space into the sinusoidal lumen through the endothelial wall. Debris was either forced through enlarged pores or through the wall, with a progressive invagination followed by an outpouching in the lumen. The force, possibly provided by endothelial massage, may not be sufficient to push out cellular debris from the Disse space; morphological data seemed to indicate that endothelial damage may be a necessary factor. Debris present in the lumen was phagocytized by numerous active macrophages. Cellular debris was not observed in the Disse space of control patients. PMID- 3105170 TI - Renal oncocytoma: immuno- and carbohydrate histochemical characterization. AB - Samples from renal and thyroid oncocytomas were studied with antibodies against intermediate filament proteins, nephron site specific antigens and nephron segment specific lectins to gather information on the immunohistological and carbohydrate histochemical features of these tumours. The results show a surprising failure of most antibodies and lectins used to react with the oncocytomas, although readily staining the surrounding normal tissue areas. No immunohistological evidence for derivation of oncocytomas from proximal tubular epithelial cells could thus be found. Instead, Triticum vulgaris (wheat germ agglutinin; WGA) and Concanavalin A (ConA) lectins were seen to stain the oncocytes specifically, suggesting that these lectins are useful to further characterize oncocytomas. PMID- 3105171 TI - Phenotypic expression of immune secretory function in focal pregnancy-like change of the human breast. AB - Fibrocystic disease of the breast in middle-aged women characteristically shows focal epithelial lesions of a very varied nature. The functional immunohistochemical changes in such lesions have been little studied. Focal Pregnancy-like Change in the breast has a striking morphological similarity to the secretory breast lobules in pregnancy and in lactation. We show that the epithelial cells in all the lesions of Focal Pregnancy-like Change studied simultaneously express secretory component, Ig A and J chain in their cytoplasm. Additionally these epithelial cells, unlike those in resting breast lobules, contain lysozyme and lactoferrin. All these phenotypic immunohistochemical changes in Focal Pregnancy-like Change resemble the breast lobules of late pregnancy and lactation. Possibly, the very focality of Focal Pregnancy-like Change reflects a peculiar and local sensitivity of 'resting' breast lobules to unidentified hormonal stimulation. PMID- 3105172 TI - Ultrastructural studies of cultured human epithelial sheets used as skin allografts. AB - In this work the ultrastructural features of cultured epithelial sheets (CES) used as skin allografts in humans are described, before and at various times after grafting. Prior to grafting, CES consisted of 4-5 layers of keratinocytes of a low to moderate degree of differentiation. However, after grafting, the CES developed progressively but rapidly features of a well-differentiated epidermis (including melanocytes and Langerhans' cells) and a dermal-epidermal junction. No evidence of rejection was observed. These results demonstrate the key role of normal dermis in the maturation of the surface epithelium and prove the suitability of CES as skin allografts. PMID- 3105173 TI - Kappa light chain nephropathy. A pathologic study. AB - Percutaneous renal biopsies from 4 patients with clinically unsuspected kappa light chain nephropathy were studied using light, immunofluorescence, and electron microscopy. The diagnosis in each case was established by demonstrating monoclonal kappa light chain deposits in basement membranes and basement membrane like structures of glomeruli, tubules, and blood vessels by immunofluorescence microscopy. Characteristic electron dense deposits occurred in every case but the intensity and distribution of electron densities did not correlate with the immunofluorescence findings. When light chain aggregation occurred, as evidenced by the distribution of electron dense deposits, it was proportional to the amount of basement membrane-like material as if these immunoglobulins had a particular affinity for structures chemically related to basement membranes. Although active tubulointerstitial lesions were prominent in all biopsies, there was considerable variation in glomerular pathology with only 1 case exhibiting the typical nodular glomerulosclerosis. Correlation of the light, immunofluorescence, and electron microscopic findings in these cases suggests that the pathogenesis of kappa light chain nephropathy is related to light chain nephrotoxicity directed to basement membrane-like structures with subsequent alterations in hemodynamics and structural renal damage. PMID- 3105174 TI - Isolated amyloidosis of the atrioventricular valves. A study of one case, curiously associated with diffuse storage of plant wax paraffin. AB - Autopsy of a 55-year-old man, whose death was due to coronary failure, revealed: localized amyloidosis limited to the leaflets of the atrioventricular valves and their chordae tendinae, with no apparent relationship to atherosclerosis, and deposits of crystallized vegetable hydrocarbons of dietary origin, mainly in the lungs, lymph nodes and liver. Observations of isolated amyloidosis in healthy valves are exceptional. The association with multi-organ deposition of vegetable wax hydrocarbons raises the question of a possible link between these two entities. PMID- 3105175 TI - Megamitochondria as a diagnostic marker for alcohol induced centrilobular and periportal fibrosis in the liver. AB - One hundred and five biopsies with centrilobular and/or portal/periportal fibrosis of different aetiology were examined by light microscopy for the presence of megamitochondria (MM). Sixty eight patients had some daily alcohol intake, 37 did not. The incidence of MM in the group with daily alcohol consumption was 49% and in the group without only 5%. Two types of MM were identified. Type I MM (round to oval) were located mainly in zone 3 and type II (needle-shaped) mainly in zone 1. Both types were related to alcoholic liver disease. PMID- 3105176 TI - [Morphologic changes and cytochrome P-450 induction in the liver of the rat after exposure to polychlorinated biphenyls in various diets]. AB - In is shown that administration of sovol, a mixture of polychlorinated diphenyls, in a dose of 500 mg/kg (about 1:10 LD50) induces pronounced changes in the rat liver structure, in particular, fat accumulation and diminution of RNA lump number in hepatocyte cytoplasma, alteration of nuclei, decrease in the number of hepatocytes and binuclear cells in the visual field. Structural disorders in the liver are observed during a long period (up to 5 months) and, to a certain extent, depend on the composition of the lipid component of the ration. Certain differences are recorded in the character of the morphological changes in the liver after single and repeated injections of the agent. No distinct relationship is recorded between the manifestation of hepatocyte fat infiltration and other morphological changes in the liver, and the index of microsomal cytochrome P-450 induction during sovol action. PMID- 3105177 TI - [Distribution of plasminogen activator and its inhibitor in the vascular bed]. PMID- 3105178 TI - [Effect of nitrogenous parenteral feeding on the protein spectrum of the blood of patients with acute pancreatitis]. PMID- 3105179 TI - Myoclonic encephalopathy in Jamaican children. PMID- 3105180 TI - [Endocrine constellation in androgenetic alopecia in the female]. AB - The mechanisms which induce androgenetic alopecia in females are only poorly understood at the molecular biological level. In predisposed, mainly centroparietal areas, androgenic stimulation of genetically predisposed hair follicles is considered to cause transformation from terminal to vellus hair follicles. However, reports on serum androgen levels in androgenetic alopecia in the female show broad variations. In the present study serum androgens, gonadotropins, oestradiol and sex hormone binding globulin were determined in the luteal phase of the menstrual cycle in 25 patients with female pattern androgenetic alopecia by radioimmunosorbent assay. In 16 of these patients skin slices from the alopecic areas were punch biopsied under local anaesthesia for determination of cytosol- and nuclear androgen receptor (AR). Mean values of all serum hormone levels were within the normal range. Cytoplasmatic AR was positive in 75% of cases, with a mean level of 22 fmol/mg protein. In 50% of cases nuclear AR was demonstrated, with a mean level of 119 fmol/mg DNA. No correlation was found between serum androgen levels and AR. Highly positive AR levels indicate a high androgen stimulability in female androgenetic alopecia. These findings support the concept of AR as regulators of genetically determined hair follicles in androgenetic alopecia. PMID- 3105181 TI - [Isolation of Neisseria meningitidis from the urethra and cervix]. AB - Meningococcal infections of the urogenital tract were considered rare until recently, but over the past few years an increasing number of cases of this hitherto uncommon infection have been reported. The rising incidence of N. meningitidis isolated from these sites has important epidemiological implications. The need for careful diagnostic procedures is emphasized. PMID- 3105182 TI - [Health management--physical therapy in chronic nonspecific airway diseases. Prevention and rehabilitation]. AB - First of all there is a description of the temporal change of a cure at a spa to a modern treatment for rehabilitation. Today treatments for rehabilitation are methods treating COLD in addition to medical care of a general practitioner or a specialist and the function of a hospital in acute and severe diseases the third practicability of treatment. Treatment in a sanatorium is preferred by social assurances. Diagnostic management and physical treatment, physical training and education in health represent an extensive medicine program. The cooperation of sanatorium of medicine rehabilitation with social workers for professional rehabilitation guarantees a transition from medical to professional rehabilitation, with the purpose to achieve an improvement for patients with bronchopulmonal handicaps in their social and professional situation. PMID- 3105184 TI - WHO Expert Committee on Drug Dependence. PMID- 3105183 TI - [Antibacterial therapy of acute exacerbated chronic bronchitis]. AB - An early therapy of the acute exacerbation is important for the long-term prognosis of chronic bronchitis. The aim of the therapy is to stop the progressive damage of the bronchial mucosa. The typical clinical symptoms and the knowledge of the usual pathogens (in at least 80% hemophilus influenzae and streptococcus pneumoniae) allow a "blind" chemotherapy with aminopenicillins, tetracyclines and the trimethoprim-sulphonamide combination as medication of choice. The treatment is successful when the purulent sputum turns mucoid within 2 to 5 days and the symptoms improve. If this does not happen, culture and antibiogram should be made and chemotherapy chosen according to the findings. The acute exacerbation can be complicated by an airway obstruction. In this case the short-term application of glucocorticoids in combination with bronchodilators and secretolytics is suggested. PMID- 3105185 TI - Difference in the effects of phenobarbital and 3-methylcholanthrene treatment on subunit composition of hepatic glutathione S-transferase in male and female rats. AB - Male rats more than seven weeks old showed significantly higher activity of hepatic cytosolic glutathione S-transferase (GST) than females. This sex-related difference in GST activities might be explained by the difference in subunit composition of the enzymes between males and females. The relative proportion of subunit composition of GST between adult male and female rats was as follows: Ya, female greater than male; Yb(Yb'), male much greater than female; Yc, female greater than male. Since phenobarbital (60 mg/kg, i.p. for seven days) induced the Yb subunit as well as Ya subunit, the enzyme activity was more increased in males than in females and the sex difference became more marked. 3 Methylcholanthrene (20 mg/kg, i.p. three times) caused an increase of Ya subunit alone, and then the increased extent was greater in females than in males, and resulted in the disappearance of sex difference. PMID- 3105186 TI - Effects of phenobarbital on the biliary excretion of aflatoxin P1-glucuronide and aflatoxin B1-S-glutathione in the rat. AB - Direct h.p.l.c. analysis of bile separated at least five major water-soluble metabolites of AFB; the two most prevalent AFB metabolites were identified as AFB S-glutathione (AFB-GSH) and AFP1-glucuronide, which accounted for 49-57% and 4 15% of total biliary AFB metabolites, respectively. In the two hours following AFB administration, phenobarbital-treated rats eliminated 50% more AFB-derived radioactivity in bile compared with controls. No qualitative differences in the profile of biliary AFB metabolites were noted between phenobarbital-treated and control rats. However, a 90% increase in the rate of excretion of AFB-GSH was found in phenobarbital-treated animals. Phenobarbital treatment had no significant effect on the amount of AFB remaining in the liver after two hours, but decreased the amount of AFB covalently bound to hepatic DNA by 55%. When individual animals from both control and phenobarbital-treated groups were considered, the correlation between the increase in excretion of AFB-GSH and the decrease in covalent binding was significant with a correlation coefficient of 0.77. This finding is consistent with the hypothesis that induction of GSH S transferase is responsible for the anticarcinogenic effects of phenobarbital towards AFB-induced hepatocarcinogenicity, although changes in the rate of formation of aflatoxin P1 or other biotransformation pathways may also be important. PMID- 3105187 TI - Induction of liver microsomal epoxide hydrolase, UDP-glucuronyl transferase and cytosolic glutathione transferase in different rodent species by 2 acetylaminofluorene or 3-methylcholanthrene. AB - Control activities vary 12-fold for microsomal epoxide hydrolase, two-fold for UDP-glucuronyl transferase and five-fold for cytosolic glutathione (GSH) transferase among the different rodents (rat, hamster, guinea-pig, mouse) examined. For all three enzymes the activities in rat liver are towards the lower values. In these rodents, except for a 100% increase in microsomal epoxide hydrolase in guinea-pig liver, 2-acetylaminofluorene induces the three phase 2 enzymes only in rat. Treatment with 3-methylcholanthrene also produces the largest effects on these three enzyme activities in rat liver; exceptions are its failure to induce microsomal epoxide hydrolase in female rat and the large induction of cytosolic GSH transferase in hamster liver. Quantitatively, hepatic microsomal epoxide hydrolase, UDP-glucuronyl transferase and cytosolic GSH transferase activities, and their inducibility by 2-acetylaminofluorene or 3 methylcholanthrene, in male Sprague-Dawley rats are not representative for other rodent species or even, in all cases, for female rat. PMID- 3105188 TI - Strain differences in the metabolic activation of aflatoxin B1 in the rat. AB - It has been reported that female Fischer rats are much more susceptible to the hepatocarcinogenic effects of aflatoxin B1 than female DA rats. Female Fischer rats are approximately twice as active as female DA rats in producing adducts of aflatoxin B1 with DNA in vivo, in freshly isolated hepatocytes and with hepatic microsomal fractions. There was no difference between the hepatic microsomal fractions from Fischer and DA rats in the production of adducts between aflatoxin B1 and microsomal protein. The difference between the strains in the formation of adducts with DNA was not due to either the activity of glutathione S-transferases or to the selective destruction of cytochrome P-450 in the DA strain. None of the differences reported here was of sufficient magnitude to explain the difference in susceptibility of the rat strains to the hepatocarcinogenic effects of aflatoxin B1. PMID- 3105190 TI - [Economic aspects of sexually transmissible diseases]. PMID- 3105189 TI - [Incidence of primary and secondary resistance of M. tuberculosis in East Germany in 1983 in hospitalized patients]. AB - The frequency of primary drug resistance in patients treated in hospital because of tuberculosis of the lung in 1983 was 2.3% (21 patients). Among them there were 5 patients (0.6%) with resistance to both INH and SM and 1 patient with a fourfold resistance. The frequency of secondary drug resistance was 20% (29 patients), among them a good third showed resistance to two or more drugs. Comparing to 1980 a decrease by half of patients treated repeatedly and also of the number of patients with secondary resistance can be recognized. Both the low share of primary drug resistance and the decrease of patients with repeated treatment indicate an effective therapy of tuberculosis in the GDR during the last years. PMID- 3105191 TI - [Distribution of the musculature of the posterior external cranial base and development of the occipital transverse torus in fossil hominids, especially in Homo erectus]. PMID- 3105192 TI - [Centrum medianum of the thalamus: review of morphofunctional organization]. PMID- 3105193 TI - Diphenylhydantoin induced granulocytopenia following a seizure prophylaxis after a depressed skull fracture. AB - The article deals with a rare case of granulocytopenia following a seizure prophylaxis after a severe head injury. Although fatal complications like the one described occur extremely seldom, we want to emphasize the necessity of regular controls during the critical time period between the 10th and the 67th day of diphenylhydantoin treatment. The blood level should not exceed 10-20 micrograms/ml to prevent any toxic reaction to the myelopoetic system. If this treatment cannot be provided, we suggest to administer Clonazepam or Convulex. PMID- 3105194 TI - Portal blood flow changes in hyperammonaemic rabbits. PMID- 3105195 TI - Effects of maturational changes upon the orientation of auricular activation vector in sheep. PMID- 3105196 TI - Maturational effects on the activation and recuperation ventricular vectors from sheep. PMID- 3105197 TI - Clinical pharmacology of cefazolin in calves. PMID- 3105198 TI - Pharmacokinetics of aditoprim, a new long-acting dihydrofolate reductase inhibitor, in heifers. PMID- 3105200 TI - [Neoplasms in poultry]. PMID- 3105199 TI - [The secretion of inorganic phosphorus in the saliva of P-depleted sheep]. PMID- 3105201 TI - Influence of halothane genotype and boar presence on puberty in gilts. PMID- 3105202 TI - Experimental intestinal obstruction in cattle. Part III: Therapy, outcome and autopsy findings. PMID- 3105203 TI - [Estimation by toads of the distance to the moving objects and their true size: neuroethological and comparative aspects]. AB - In two sets of experiments, studies have been made on the parameters by which the toad Bufo bufo estimates the neighbour and remote moving objects. In absence of the structural surrounding, a dark target with a diameter 17.2 degrees (3 cm at a distance of 10 cm) and with the rate of movement 36, 72 and 145 degrees/sec evoked in toads only feeding turns; at the rates 72 and 145 degrees/sec, together with these turns, animals usually fired with their tongues to the direction of the target, revealing evident underestimation of the distance and real size of the object. Under the same experimental conditions, a target with a diameter 1.2 degrees (0.25 cm at a distance of 12 cm) and the rate of movement 0.6 and 3 degrees/sec produced mainly frightful reaction, which indicates overestimation of the distance to the object and its size. The same object moving at a structural background evoked only feeding reactions, i.e. the animals correctly estimated the distance to the target and its size. PMID- 3105204 TI - [Immunological research and criteria for determining the etiology of acute bronchitis in young children]. AB - In the determination of the etiology of acute bronchitis in children, a complex of microbiological and immunological methods should be used. The isolation of Streptococcus pneumoniae and Haemophilus influenzae at a concentration of greater than or equal to 10(4) cels/ml from tracheobronchial washings is the early and most significant method for the determination of the etiology and therapy of acute bronchitis. On the basis of microbiological and immunobiological criteria, the etiological role of S. pneumoniae has been determined in 78% of patients and that of H. influenzae, in 48% of patients, mainly in association with pneumococci. PMID- 3105205 TI - Unusual renal involvement during diabetic ketoacidosis (DKA) in a newly diagnosed type I diabetic child. AB - A 10-year-old boy, in a precomatose state, was admitted to our Endocrine Unit for diabetic ketoacidosis. It took unusually long to reequilibrate the acidosis despite a bicarbonate drip. On the 4th day the patient suddenly complained of an acute abdominal pain associated with macrohematuria and oliguria; ankle edema was evident. No radio-opaque image was detected along the urinary tract. An intravenous pyelogram (IVP) showed an almost totally silent left kidney. Ten days later a control IVP showed complete normality of both kidneys. We postulated that the serious and protracted dehydration might have resulted in the formation of a blood clot along the renal tract and that the rehydration may have subsequently removed it. PMID- 3105206 TI - Thyroid hormone reserve in asymptomatic autoimmune thyroiditis. AB - Basal (B) and peak (P) serum levels of thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3), free triiodothyronine (FT3), and TSH were measured before and after oral TRH (40 mg) administration in 79 subjects affected with asymptomatic autoimmune thyroiditis (AAT) and in 69 normal subjects. The area under the curve (AUC) and peak values of T4, FT4, T3 and FT3 were considered as parameters of thyroid hormone reserve. Intrathyroidal iodine (ITI) was measured by the X-ray fluorescence method. The AAT subjects were divided into three groups on the basis of their basal and peak TSH values. In group I, these parameters were similar to those in the normal controls; in group II, basal TSH remained normal but peak TSH was significantly increased, and in group III both values were significantly increased. Group I differed from the controls by a decrease in P FT4 and AUC FT4, whereas in groups II and III B FT4 was also significantly lowered. T3 levels were similar in all groups except in group III, in whom they dropped. ITI was already lower in group I than in the controls. Its decline went further in groups II and III. An inverse correlation with significant r values was evidenced between log B and P TSH on one hand and log B FT4, P FT4 and AUC FT4 on the other. When group III was excluded, log P TSH was positively correlated with log B T3, P T3, AUC T3, and AUC F T3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105207 TI - Molecular genetical examinations of multiple myeloma and other B-cell malignancies. PMID- 3105208 TI - M protein idiotype in patients with monoclonal gammopathies. PMID- 3105209 TI - Circulating immunoglobulin secreting cells in patients in the premyelomatous state. PMID- 3105210 TI - Colony assay in patients with multiple myeloma--relationship between colony growth and clinical stage. PMID- 3105211 TI - Differential distribution of sialic acid in exocrine pancreas and parotid gland. AB - The sialic acid-specific lectin limulin (LPA, from Limulus polyphemus hemolymph) was used for the investigation of the distribution of accessible sialoglycoconjugates on the surface of cells from rat and rabbit parotid gland and exocrine pancreas. Fluorescence microscopy with rhodamine-conjugated LPA on fresh-frozen and fixed-frozen sections of the parotid gland revealed lectin binding sites on acinar and ductular epithelial cells. The staining was localized only at the periphery of the acini and ducts and was absent from the apical and lateral surface of epithelial cells. This staining pattern contrasted with that found in epithelial cells of acini and ducts in exocrine pancreas, where the luminal surface was intensely labeled by the fluorescent lectin. The luminal content of ductular tract and acini in parotid gland and pancreas was devoid of lectin-reactive sialoglycoconjugates. Connective tissue surrounding ducts and blood vessels bound the lectin heavily in both glands. These results outline that cells with similar structure and function, but constituents of different exocrine glands, exhibit differential distribution of sialoglycoconjugates on their corresponding plasmalemmal domains. PMID- 3105212 TI - Immunohistochemical demonstration of glial fibrillary acidic protein (GFAP) in nasal gliomas. AB - Using the Sternberger method (Immunoluk Histoset KIT) GFAP (glial fibrillary acidic protein) was demonstrated immunohistochemically in 4 nasal gliomas. In these histologically complex tumour-like lesions mesenchymal, epithelial, and neuroglial tissues as well as small groups of scattered glial elements could be differentiated specifically by the highly sensitive GFAP immunoperoxidase technique. GFAP was present in astrocytes and astrocyte-like differentiations. The reactivity of cell processes was essentially lower. The GFAP immunostain does not always correlate with Mallory's phosphotungstic acid hematoxylin (PTAH) stain and Gallyas' silver impregnation method for astrocytes. Additionally the immunohistochemical investigation of semithin sections prepared by the so-called pop off technique after Bretschneider et al. (1981) allows the correct localization of GFAP in astrocytes and their modulations. Furthermore, in this study, the intimate connection of epithelium and glial cells as well as astrocytes containing hemosiderin granules could be demonstrated. The latter findings suggest a possible phagocytotic activity of astrocytes. Our results show that the demonstration of GFAP by the Sternberger method is a valuable aid in establishing astrocytic glial differentiations and modulations in complex tumour like lesions such as nasal gliomas. PMID- 3105213 TI - [3 beta-Hydroxysteroid-dehydrogenases of the testis and epididymis of the Peking duck (Anas platyrhynchos L.)]. AB - This study is concerned with the histochemical activity of hydrosteroid dehydrogenases (HSD), glucose-6-phosphate dehydrogenase (G6PDH), and 6 phosphogluconate dehydrogenase (6PGDH) in testis and epididymis of 20 male Pekin ducks. Various 3 beta-HSD, the G6PDH, and the 6PGDH were localized in these organs. 3 beta-etiocholane was much quicker utilized by the 3 beta-HSD than epiandrosterone, dehydroepiandrosterone, and androstendiol. The capability of testis Leydig cells of utilizing the 3 beta-etiocholane was higher in winter than in summer. The G6PDH and the 6PGDH in the Leydig cells and basal cell layer of the tubuli seminiferi contorti were active throughout the year. There was weak 3 beta-HSD activity in the epithelia of the ductuli efferentes distales and in the ductus epididymidis from March to June. The G6PDH and the 6PGDH showed positive reaction in the rete testis and ductuli efferentes proximales throughout the year. The 3 beta-HSD activity in testis and epididymis is saisonally different: In summer, there is no 3 beta-HSD activity in both organs. In winter, the 3 beta HSD is demonstrable in the testis but not in the epididymis. In spring, there is 3 beta-HSD activity in the epididymis but not in the testis. PMID- 3105214 TI - Problems with ultrastructural demonstration of aryl sulphatase activity in rat liver parenchymal cells. AB - The classical method for the electron microscopical demonstration of aryl sulphatase activity in lysosomes (Hopsu-Havu et al. 1967) has been applied for selective demonstration of lysosomes in rat liver parenchymal cells. A positive reaction was obtained in some lysosomes, but the greater part of the precipitate was found in the form of big conglomerates which frequently filled up the interstices between various organelles rather than that they were localized within the organelles. Modifications of the procedure in order to try to confine the demonstration of enzyme activity to lysosomes only included measures: To reduce the amount of primary reaction product, to improve the trapping efficiency of the incubation medium, to prevent possible displacement of the final reaction product. Extralysosomal precipitate persisted under all circumstances; this is interpreted as an artefact rather than as a demonstration of enzyme activity localized in vivo in the cytoplasmic matrix. It is concluded that the present method for demonstration of aryl sulphatase activity is not well suited for microscopical identification of lysosomes in rat liver parenchymal cells. PMID- 3105215 TI - Lectin binding patterns in amphibian epidermis. AB - A battery of 6 different horseradish peroxidase conjugated lectins has been employed for structural localization of glycoconjugates in amphibian epidermis. Lens culinaris (LCA) lectin stained the basal membrane and gave no significant reaction on the epidermal layers. Canavlia ensiformis (Con A) and Griffonia simplicifolia II (GS II) lectins bound the keratinocyte cytoplasm and the basal membrane as well. Ulex europaeus I (UEA I) lectin had only reactivity with flask cells. Griffonia simplifolia I (GS I) and Glycine max (SBA) lectins preferentially bound the cell membranes of keratinocytes, being the intensity of the staining gradually increasing from the stratum spinosum to the stratum granulosum. These results show that UEA I, GS I, and SBA are good markers to distinguish different cell types and the degree of keratinocytes differentiation. PMID- 3105216 TI - Estrogen binding sites and estrophilin histochemistry and their correlation with oestrogen receptor biochemistry. AB - Since the application of mono- and poly-clonal antibodies to the estrogen receptor protein (estrophilin) classically admitted opinions about the interactions between estrogens and their target cells have changed. Biochemical assays of ER have been shown to provide false negative results; the key-mechanism seems to be located at the nuclear level, while until now most emphasis was put on cytosolic ER. In histochemistry, apparently contradictory reports have emphasized either cytoplasmic or nuclear labelling of estrogen binding sites (EBS). A lot of supputations have tried to explain in vitro translocations from the cytoplasm to the nucleus according to the physicochemical conditions which were used. Reading of some articles gives the impression that EBS histochemistry is yet an established and reliable method; commercially available histochemical "kits" may support this false idea. Therefore it is absolutely mandatory to intend to remain cautious and critical. Stepwise our knowledge is increasing; it is absolutely clear that the problems which did rise thanks to the "contradictory" histochemical studies gave a new impetus to both biochemical and histochemical research. Immunohisto- and cyto-chemistry of EBS and estrophilin go on in parallel and in correlation with biochemistry. PMID- 3105217 TI - Light microscopical localization of enzymes by means of cerium-based methods. V. Optimization of the cerium-lead (Ce-Pb)-technique for alkaline phosphatase. AB - A modification of the earlier published cerium-based technique for histochemical detection of alkaline phosphatase activity at light microscopical level (Halbhuber and Zimmermann 1985) is described. The reduction of the s-collidine concentration from 200 mmol to 50 mmol, increase of cerium ion concentration rom 1 mmol to 5 or 10 mmol, and sucrose concentration from 7.5% to 15% at increased from pH = 9.0 to 9.5 less than or equal to 9.9 in the incubation medium led to a high intensification of the histochemical reaction. The brush borders of the rat kidney (especially of the epithelial cells of the primary convoluted tubules) and of the enterocytes demonstrate black-brown tinged and precisely localized final reaction products. Moreover, a simplification of the histochemical procedure by employment of postfixed cryostat sections (small intestine) instead of the time consuming perfusion fixed material (kidney) is presented. Several fixatives were also tested. Nakane's periodate-lysine-paraformaldehyde (PLP) or the periodate lysine-glutaraldehyde (GLP) fixations are superior to the classical glutaraldehyde/paraformaldehyde double fixation. The proposed optimized cerium based techniques are recommended for a broad use. PMID- 3105218 TI - Rapid screening method for monoclonal antibodies against cytoskeletal proteins. AB - A horseradish peroxidase/anti-horseradish peroxidase monoclonal mouse antibody complex was prepared and used for the detection of mouse monoclonal antibodies against proteins of the whole cytoskeleton. A rapid qualitative assay of large number of antibody samples on the whole cytoskeleton and an early determination of their specificity by the immunoblot technique is described. PMID- 3105220 TI - Intensive care: cost and benefit. AB - This study presents a review of 961 patients treated in the general intensive care unit (ICU) of Akershus Central Hospital (ACH) from 1978 to 1981, including also a follow-up study of the 419 patients treated in 1978 and 1979 who were observed for an average period of 20 months after admittance to the ICU. The ICU patients represented 1.7% of all the patients admitted to the referring departments. Approximately 2/3 (67.3%) of the patients were surgical patients, representing 2.9% of the patients treated in that department, 19.6% were medical patients, and 8.6% came from the department of pediatrics. Surgery was the main reason for ICU admittance in 48.1% of the patients; in 70% of these, surgery by itself made postoperative intensive care necessary. Acute or chronic cardiovascular or respiratory disorders caused or contributed to ICU admittance in 78% of the patients; disorders of the nervous system (29.0%), gastrointestinal system (25%), and severe infections (28%) came next. The average stay in the ICU was 6.2 days. The patient's need for observation, nursing and therapy was assessed daily according to a care grade scale from 1 to 5, with 5 as maximum effort. The average care grade during the stay, multiplied by the duration of stay in days, gave the care product, which was used as an expression of the patient's need for ICU resources. The sum of care products for all the patients through 1 year thus expressed the total work load on the ICU. The ICU budget for 1 year, divided by the total care product for the same year, and thereafter multiplied by the care product for single patients or patient groups, was used as the basis for calculation of ICU costs. Patients receiving mechanical ventilation required 95% of the total work load in the ICU, and 66.3% of these efforts were directly associated with the ventilator treatment period as judged by the care product. Complications to treatment were recorded in 7.3% of the patients, and four of these patients dies of such complications. Improvement by intensive care was achieved in 81.4% of the patients, 5.2% were unchanged, and 13.4% died while in the ICU. Mortality was 9.5% below and 19.3% above the age of 60 years. Of the 419 patients who were followed for an average period of 20 months after admittance to the ICU, 56 died in the ICU, 28 died later during the same stay in ACH, and another 47 died after discharge from ACH, whereas 288 (68.7%) were still alive.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3105219 TI - Blood vessel endothelia in rat brain following experimental administration of BCNU (carmustine): karyometric studies and cytophotometric studies on DNA. AB - Studies on the effect of BCNU (Carmustine), administered in 4 intraperitoneal injections of 7.5 mg each, on cell nuclei of blood vessel endothelia were performed on the parietal cortex and the thalamus of 20 adult rats of Wistar strain. Karyometric studies demonstrated increased circumference and cross section area of cell nuclei in vascular endothelia following administration of the cytostatic drug. The nuclei acquired a more spheric shape and a decreased surface irregularity (decreased folding) of their cross-sections. Extinction of endothelial cell nuclei estimated following administration of BCNU showed also an increased content of DNA as well as a more compact and concentrated nuclear chromatin. The alterations noted in endothelial nuclei of thalamic blood vessels were more pronounced than those seen in the parietal cortex. PMID- 3105221 TI - The use of alfentanil (Rapifen) by infusion for surgical procedures of long duration. AB - The use of alfentanil was studied in 49 patients undergoing surgery with a duration of at least 90 minutes. Induction was performed with droperidol (Dehydrobenzperidol) and etomidate (Hypnomidate), maintenance with nitrous oxide/oxygen 2:1 and alfentanil. Alfentanil was administered as an initial bolus of 2-3 mg depending on the body weight of the patient, immediately followed by a continuous infusion of 0.75 microgram/kg/min. In case a stressful or painful event in surgery caused inadequate analgesia, additional increments of 1 mg of alfentanil were administered. Anesthesia was considered to be good in 90% of the patients. The number of additional increments needed did not increase as the anesthetic procedure progressed in time. In virtually all patients postoperative recovery was fast and not related to the number of increments. It is concluded that alfentanil infusion for longer procedures in combination with nitrous oxide/oxygen provided a good and easy method for maintaining a satisfactory level of analgesia. PMID- 3105222 TI - The effect of alfentanil on experimental myocardial infarction size: a comparison with fentanyl and halothane. AB - We compared the action of alfentanil on experimental myocardial infarction size with two widely used anesthetic drugs: fentanyl and halothane. Myocardial infarction size, measured by histological techniques, was identical for the three drugs investigated. Our results demonstrate that the action of alfentanil on factors governing myocardial oxygen supply and demand in the rat with coronary artery ligation is no different from the action of fentanyl or halothane. PMID- 3105223 TI - Evaluation of arterial blood sampling using the B 109 syringe (radiometer). AB - Arterial blood gas measurements were performed after sampling with two different syringes (B 109 Radiometer and "ONCE" ASIK) and storage of the samples at 0-4 degrees C for 15 min. The blood samples were analysed in an ABL3 blood gas analyser. We found no statistically significant difference between the mean PaO2, PaCO2 and pH values with either technique of sampling. The B 109 syringe does not offer any advantages over the common plastic 2.5 ml. syringe ("ONCE"). PMID- 3105224 TI - [Treatment of leprosy by human metabolites]. AB - We are interested for other human metabolites than desoxyfructo-serotonin (DFS), showing antileprosy activity. This is the case of desoxyfructo-5 hydroxytryptophan and of some liposoluble derivatives of DFS. The time of resorption and penetration into M. leprae infected tissue, is very different for these metabolites. For this reason the simultaneous application of these compounds may represent some advantage in the treatment of multibacillar form of leprosy. The use of DFS together with the antileprosy diet "NAL" have the supplementary advantage to stabilize the DFS level in the serum during the treatment. PMID- 3105225 TI - Changes of adenovirus hexon associated with different passage history of Ad h 1. AB - Two descendants of the prototype strain AD71-Washington D. C. were obtained by independent passaging for at least 18 years in Kiev, and in Budapest (Ad h 1 kappa, and Ad h 1B, respectively). By restriction endonuclease mapping, the DNA was identical corresponding to the patterns of human adenovirus type 1. In spite of this, SDS-polyacrylamide gel electrophoresis revealed that the purified hexon of Ad h 1 kappa was of lower Mr than the subunit of Ad h 1B. In contrast to this, the native capsomer (hexon) of Ad h 1 kappa exhibited lower electrophoretic mobility in agarose gel electrophoresis than the native hexon of Ad h 1B. Oligopeptide mapping of the main hexon bands from SDS-polyacrylamide gels revealed the presence of unique spots among the chymotryptic oligopeptides of Ad h 1B, too. Thus, the differences in the sensitivity to proteolytic cleavage during purification seem to have a structural basis. Antigenic analysis of the native hexon capsomers was performed using polyclonal antihexon immunsera. Immunodiffusion, immunoelectrophoresis, and competitive RIA were used for comparison. The results indicate that native hexon capsomers of Ad h 1 kappa and Ad ha 1B possess antigenic differences within the type-specific regions, nevertheless, their genetic background could not be detected by the restriction endonucleases applied. It cannot be excluded that the differences were results of altered assembly of virions under different passage conditions. PMID- 3105226 TI - Immunochemical and immunological study of cell-wall proteins of Pseudomonas aeruginosa. AB - Crude aqueous extract was obtained from acetone-dried cells of Pseudomonas aeruginosa strain 868 (serogroup O2, Lanyi and Bergan's schema) and subjected to ultracentrifugation (105,000 g, 3 h); the lipopolysaccharide (LPS)-containing precipitate was discarded and the supernatant containing water-soluble cell proteins was subjected to further fractionation. From a partially purified aqueous extract two fractions were obtained by step-wise precipitation with ammonium sulphate, namely, F1 (by 50% saturation), and F2 (by 80% saturation). By gel and ion-exchange chromatography from both fractions 9 subfractions were isolated differing in molecular weight, protein content, and LPS contamination. Subfractions 4 and 7 were practically free from LPS, and gave one precipitation line with antisera for strain 868. By immunoelectrophoresis subfraction 4 contained 2 cathodic and 1 anodic, whereas subfraction 7 mainly 1 anodic component. These subfractions were antigenically identical. With ELISA these subfractions were less active as compared to other subfractions, in particular to those of high molecular weight. The anti-subfraction 4 and anti-subfraction 7 sera were found to protect passively mice against intraperitoneal challenge by P. aeruginosa strain 8 (serogroup O2). These data support the authors' opinion that subfraction SF-4 and SF-7 are protective protein antigens (mol wt about 40,000 and 30,000, respectively), that are localized in the outer membrane of P. aeruginosa cell envelope. PMID- 3105227 TI - Effect of heat treatment on phage susceptibility of a Mycobacterium smegmatis strain. AB - Plating efficiency of mycobacteriophage butyricum (By) proved to be 10(-4)-10(-3) on Mycobacterium smegmatis strain Rabinowitz (M. sm. R.) cells being in the logarithmic phase. This increased to 10(-2)-10(-1) when the cells were held at 50 57 degrees C for 2 h before infection. After replacing the cells to 37 degrees C, plating efficiency of the phages returned to the starting values. This phenomenon could be inhibited by nalidixic acid (150 micrograms/ml) and chloramphenicol (10 micrograms/ml) but not by mitomycin C (0.05 microgram/ml). No return to the starting plating efficiency values were observed, if incubation of cells at 37 degrees C after heat treatment has been performed in buffer. The data suggest that By phage propagation in M. sm. R. cells is inhibited by a thermosensitive protein. PMID- 3105229 TI - [A case of melorheostosis treated with a diphosphonate]. PMID- 3105228 TI - Selective localization of gamma-enolase in stromal cells of cerebellar hemangioblastomas. AB - Three cases of cerebellar hemangioblastoma were studied using the immunoperoxidase technique to localize gamma-enolase, also known as neuron specific enolase. The stromal cells demonstrated positive staining for gamma enolase, while endothelial cells and pericytes showed no reactivity. Two vascular lesions, an angiosarcoma and a cutaneous angioma, were studied and found to be nonreactive for gamma-enolase. All tumors were also tested for factor VIII/von Willebrand factor, glial fibrillary acidic protein, and the S-100 protein. The lack of expression of gamma-enolase in endothelial cells of hemangioblastomas demonstrates a clear antigenic distinction from neighboring gamma-enolase positive stromal cells. The significance of this finding and its implications for stromal cell histogenesis are discussed. PMID- 3105230 TI - The vestibular blood flow during CO2-breathing in rabbits. AB - The microsphere method was used to measure the inner ear blood flow in albino rabbits before and during artificial ventilation with 5% CO2 in air. An increase in blood flow resulted in both the cochlear and the vestibular parts of the inner ear. PMID- 3105231 TI - Bacteriology in peritonsillitis. AB - Abscess material from 10 patients with peritonsillar abscesses was obtained by aspiration. Beside cultures and cultures in the laboratory, were performed 3-26 hours later, as well as routine nasopharyngeal and throat swab cultures. A total of 26 bacterial species were isolated from the abscess material; 19 of these were obligate anaerobes. In 4 patients a pure growth of anaerobes was found. In 3 patients a mixed aerobe/anaerobe flora was obtained. In 3 patients a pure growth of aerobes was found. Beta-hemolytic streptococci groups A and C respectively were isolated from 2 patients, but in pure culture from one patient only. The results of the nasopharyngeal and throat swab cultures showed a poor correlation to the results of cultures on aspirates. Comparison of the results of the bedside inoculation with the results of inoculation in the laboratory showed a moderate loss of bacterial species, viz. 3 of 26. All bacteria studied were susceptible to penicillin V, ampicillin and erythromycin when tested in vitro. PMID- 3105232 TI - The effect of carbon dioxide on the activity of cilia. A study on rabbit sinus mucosa in vitro. AB - The relation of ciliary activity to the partial pressure of carbon dioxide was studied with a photoelectric method on rabbit sinus mucosa in vitro. A dose response relationship was found, where by ciliary activity was impaired at pCO2 above 5 kPa. The effect of elevated partial pressure of carbon dioxide on ciliary activity in secretory otitis media and sinusitis is discussed. PMID- 3105233 TI - The suprastructure of the saccular macula. AB - Inclusion of tannic acid in the primary fixative fortuitously preserved the macular suprastructure, from the macular surface to the otoconia, in rat. Results demonstrate that fluid-filled channels around the stereociliary tufts and a slit like space immediately above the macula are artefacts of tissue preparation. Filaments fill the area between, and show linkage to, the macular surface and the more peripheral, closely knit layer identified here as the true otoconial membrane. The material also passes through the otoconial membrane at various sites to surround the otoconia and extends well beyond the maculas in all directions. Although it may prove later to be endolymph, it is referred to here as supramacular substance. Kinocilia and the tallest stereocilia as well as the otoconia are tethered to the otoconial membrane. Findings were confirmed in decalcified material. Results are discussed in terms of functional and biochemical implications, and by analogy to man-made acceleration sensing devices. PMID- 3105234 TI - Gut hormones and 'minimal enteral feeding'. AB - Previously we have identified multiple surges in plasma concentrations of gut hormones postnatally in enterally fed term and preterm infants. In this study on 104 preterm infants we have shown that such surges are induced after ingestion of very small quantities of human milk. Whereas 6-day-old exclusively parenterally fed infants showed no postnatal elevation in enteroglucagon, gastrin, GIP, motilin and neurotensin, infants recovering from hyaline membrane disease who had received restricted enteral nutrition had similar hormone surges to those seen in well infants on full enteral feeds. Significant elevations in enteroglucagon, gastrin and GIP occurred after a cumulative mean enteral feed volume since birth of only 24 ml (12 ml/kg body weight) had been consumed and after a mean total intake of 96 ml (50 ml/kg) the response was maximal. Greater feed volumes were required to produce a neurotensin or motilin surge, but even these volumes were substantially lower than those required for full enteral feeding. In view of the proposed roles of gut hormones in the adaptation to extrauterine nutrition these data have implications for mammalian biology and raise the possibility that 'minimal enteral feeding' might have a clinical therapeutic role in infants undergoing prolonged parenteral nutrition. PMID- 3105235 TI - Influence of valproic acid on the gonadotropin-releasing hormone test in puberty. AB - Twelve epileptic adolescents on valproate (VPA) treatment were studied by means of clinical observation and gonadotropin-releasing hormone stimulation (GnRH) tests. Five patients were investigated before and during VPA treatment. Before treatment the basal and peak levels of gonadotropins were appropriate for age; during treatment both levels were depressed and the areas under the curves were significantly decreased. The long-term effect of VPA was studied in an additional seven patients. The basal levels of gonadotropins were as low and their response to GnRH as poor as in the second test of the first five patients--i.e., during VPA treatment. No recovery was noted in two patients after dose reduction or in a further two patients 10 months after the discontinuation of VPA treatment. In all the patients, however, the usual clinical signs of pubertal development and maturity were unaffected by VPA treatment. The significance of the results for sexual development and fertility is therefore uncertain. PMID- 3105236 TI - Does centralized treatment of cystic fibrosis increase the risk of Pseudomonas aeruginosa infection? AB - Two hundred and forty Danish patients with cystic fibrosis (97% of the total CF population in Denmark) participated in a point-prevalence study of Pseudomonas aeruginosa infection. One hundred and ninety-two patients were treated at the Danish CF centre and 48 patients were treated in other places. The age distribution was significantly different as no patients older than 19 years were found in the non-centre group. Pathogenic bacteria were isolated from the sputum of 96% of the patients. P. aeruginosa was more prevalent in patients from the centre, whereas Staphylococcus aureus was more prevalent in the non-centre group. No difference in serogroup and phage pattern of P. aeruginosa was found. There was a tendency that non-centre treated patients acquired chronic broncho pulmonary P. aeruginosa infection later, but at the age of 16 years 90% of all patients will be chronically infected. Chronic P. aeruginosa infection was significantly more common in the age group 10-14 years at the centre than outside the centre. It is not possible to prevent chronic P. aeruginosa infection in CF patients treated in small groups and because of the better prognosis of centralized treatment the latter must be recommended. PMID- 3105237 TI - Home parenteral nutrition in infantile short bowel syndrome. PMID- 3105238 TI - Ectopic thyroid gland and thyroxine-binding globulin excess. AB - A female infant with an ectopic thyroid gland and thyroxine-binding globulin excess is described. The infant presented clinically with hypothyroidism while biochemically a falsely high serum thyroxine level posed therapeutic problems. PMID- 3105239 TI - Neonatal fat digestion and lingual lipase. AB - Lingual lipase (LL) activity, pH, and products of fat hydrolysis were determined in gastric aspirates from preterm infants who received formula milk feeds by a nasogastric tube. In 1-hourly (n = 9), 2-hourly (n = 8) and 3-hourly (n = 9) fed infants LL activity increased to reach its maximum value at 60, 90, and 120 min respectively after the feeds, and gastric pH levels fell from about 6.0 to less than 3.5. There was a reduction in triglyceride content to 50% of the initial value, measured immediately after a feed, and the products of hydrolysis were mainly diglycerides and FFA. In a subsequent study 3-hourly fed infants (n = 8) had a tube feed followed by a bottle feed, and then a bottle feed followed by a tube feed on successive days (cross-over). The LL activity observed after a bottle feed (mean maximal value 23.8 mumol FFA/ml/h) was significantly higher than after a tube feed (19.1 mumol FFA/ml/h). It is suggested that substantial triglyceride hydrolysis takes place in the stomach due to lingual lipase, and sucking seems to enhance enzyme production. PMID- 3105240 TI - Plasma growth hormone (GH) responses to growth hormone releasing factor (hp GRF 1 44) in familial GH deficiency. AB - In four children with familial GH deficiency peak and integrated GH responses to an acute intravenous bolus of hp GRF 1-44 were lower than in 18 children with non familial idiopathic GH deficiency and in 5 children with structural hypothalamic abnormalities. It is possible that the familial forms of GH deficiency described may be due to absence or biological inactivity of endogenous GRF or possibly GRF receptor or post receptor abnormalities. PMID- 3105241 TI - Immunoreactive anionic trypsin and anionic elastase in human milk. AB - Immunoreactive anionic trypsin and anionic elastase have been demonstrated in human milk, by immunodiffusion and immunoelectrophoresis. Cationic trypsin and cationic elastase could not be detected by these methods. The anionic trypsin is probably present in complex with IgA. No benzoyl-DL-arginine-p-nitroanilide (BAPNA) splitting activity was found in human skim milk. Anionic trypsin was isolated by immunoadsorption chromatography. The purified enzyme had a BAPNA splitting activity. PMID- 3105242 TI - Effects of regular inhalation of beclomethasone dipropionate and sodium cromoglycate on bronchial hyperreactivity in asthmatic children. AB - The efficacy of beclomethasone dipropionate (BDP) was compared with sodium cromoglycate (SCG) and placebo in a double-blind parallel group study of 30 asthmatic children over a two-month period. All the three treatment groups received salbutamol concomitantly. Lung volumes, airway mechanics and the nonspecific bronchial hyperreactivity to carbachol were measured at the beginning and the end of the study. Two patients were excluded because of unequal clinical conditions at the entry and the end of the study and three because of lack of co operation. Three patients (1 on SCG, 2 on placebo) dropped out because of worsening clinical symptoms. The improvement in airway mechanics shown by the group treated with BDP (n = 7) was significantly greater (p less than 0.01) than in the group treated with SCG (n = 8). Nonspecific hyperreactivity to carbachol improved significantly in the BDP group (factor 5.9) compared to the SCG group (factor 1.9). Childhood asthma seems to be better controlled by a combination of BDP and salbutamol, than by SCG and salbutamol. PMID- 3105243 TI - The antibacterial effect of selected phenothiazines and thioxanthenes on slow growing mycobacteria. AB - The aim of the present investigation was to illustrate the antibacterial effect of various phenothiazine and thioxanthene derivatives on mycobacteria in vitro. It was demonstrated that clopenthixol is about twice as potent as chlorpromazine (CPZ) and levomepromazine-maleate is about half as potent as CPZ, measured by the inhibitory effect on the growth of the mycobacterial strains. Measured in the same way the stereoisomeric compounds of flupenthixol are shown to be more potent than the stereo-isomeric compounds of clopenthixol and chlorprothixen. The two last-named compounds are equal in potency. The stereo-isomeric analogs of the thioxanthene derivatives are equal in antibacterial potency against the slow growing mycobacteria. The mycobacterial strains investigated show no difference in sensitivity between the cis (Z)--and and trans (E)--compounds of the thioxanthenes. It seems particularly promising that also the more resistant mycobacteria other than Mycobacterium tuberculosis, e.g. M. avium and M. intracellulare, are sensitive in the concentration range investigated. Considered as a whole, these results might be a stimulus to investigate the antimicrobial effect of the thioxanthenes in vivo. PMID- 3105244 TI - Protein I serotype of serum-resistant versus serum-sensitive Neisseria gonorrhoeae strains. AB - In order to characterize serum-resistant and serum-sensitive strains of N. gonorrhoeae, the protein I serotype, auxotype, and penicillin susceptibility of 128 strains were tested. Sensitivity to the complement-dependent bactericidal activity of normal human serum was highly associated with protein I serotype (p less than 0.001). Thus 85% of serotype 1-3 strains were serum-resistant, whereas 86% of serotype 8 strains and all strains with serotypes 8 + 9 or 9 were serum sensitive. Serum-resistance or sensitivity for a given serotype was independent of auxotype. The susceptibility to penicillin within the serotypes 1-3 was significantly associated with auxotype (p = 0.0016); all AHU- (requirement for arginine, hypoxanthine and uracil) strains had MICs of penicillin of 0.04 microgram/ml or less and were serotypes 1-3. Among the non-AHU-strains, serotype 9 was significantly more penicillin susceptible than the other serotypes (p less than 0.003). PMID- 3105245 TI - Changes in serotype caused by cell to cell contact between different Pseudomonas aeruginosa strains from cystic fibrosis patients. AB - Two Pseudomonas aeruginosa strains, one monoagglutinable and one polyagglutinable, isolated from cystic fibrosis patients were grown in mixed culture. The strains were then separated by means of their azlocillin susceptibility and a number of colonies were tested for serotype and phage type. Changes from monoagglutinable to polyagglutinable reaction and vice versa were observed. The monoagglutinable strain was able to perform bacteriophage infection of the polyagglutinable strain, but no free phages were released. If the donor strain was to produce plaques on the receptor strain, the presence of bacteria belonging to the donor strain was essential. PMID- 3105246 TI - In vitro activity of amifloxacin (WIN 49,375) compared with those of ciprofloxacin and ofloxacin. AB - The in vitro activity of the novel fluoroquinolone derivative, amifloxacin (WIN 49,375), was compared with the activities of ciprofloxacin and ofloxacin. A total of 500 clinical isolates of Gram-negative and Gram-positive bacteria were included, and the minimal inhibitory concentration (MIC) was determined by an agar dilution method. All drugs were highly active against Enterobacteriaceae, but ciprofloxacin showed the highest activity on a weight-for-weight basis (MIC 90% less than or equal to 0.03 mg/l). Ciprofloxacin was the most active agent against Pseudomonas isolates; all isolates being inhibited by 0.25 mg/l or less. The staphylococcal isolates were inhibited by ciprofloxacin and ofloxacin at relatively low concentrations (MIC 100% = 1 mg/l), whereas amifloxacin showed moderate activity against the majority of these isolates. Ciprofloxacin was highly active against enterococci, ofloxacin was moderately active, and amifloxacin was inactive. All Neisseria gonorrhoeae isolates were susceptible to the lowest concentrations of the agents that were employed in the study (0.03 mg/l). PMID- 3105247 TI - Susceptibility testing of 7 antibiotics against anaerobic bacteria: comparison of 2 different media and carbon dioxide concentrations. AB - Anaerobic agar (AA) and Danish Blood agar (DBA) were evaluated by a standardized agar diffusion and agar dilution test in 5% CO2. The activity of seven antibiotics (tetracycline, clindamycin, metronidazole, rifamycin, chloramphenicol, penicillin, erythromycin) was tested against 40 anaerobic bacteria, including 3 control strains (Cl.perfringens ATCC 13124, B.fragilis ATCC 25285, B.thetaiotaomicron ATCC 29741). 70% of the strains were resistant to erythromycin in 10% CO2, only 30% in 5% CO2. No evident CO2-effect could be seen with the other antibiotics. Mean MIC for tetracycline was twice as great on AA than DBA. In spite of that, tablet sensitivity testing with tetracycline on AA proved to be more accurate and completely separated the resistant and susceptible strains. For penicillin, the mean MIC was one dilution step higher on AA. No major differences could be seen with the other antibiotics. AA was superior to DBA in providing growth of anaerobes. Measurement on AA was easier, and it was more precise. Except for tetracycline. MIC on control strains fell well within range set by The National Committee for Clinical Laboratory Standards (NCCLS) on AA. Acceptable correlation coefficients were recorded between agar diffusion and agar dilution. Prediction of susceptibility based on zone diameter measurements was very good on AA. Only one discrepancy that could cause change of susceptibility status occurred on AA, while there were 12 on DBA. On DBA, there was poor correlation between MIC, compared with earlier results on the same agar. The 50% inhibitory concentration (IC50) was also measured, but offered no advantage over MIC. PMID- 3105248 TI - Effect of Pseudomonas aeruginosa proteases on human leukocyte phagocytosis and bactericidal activity. AB - The effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (Ela) on neutrophil phagocytosis and bactericidal activity was examined. It was found that both proteases reduced the phagocytic activity of the leukocytes against P. aeruginosa, whereas they had little effect on the phagocytosis of S. aureus. AP and Ela at concentration of up to 250 micrograms per ml (much higher than the levels detectable under in vivo conditions) did not interfere with the bactericidal activity of the leukocytes against both test organisms. Inhibition of phagocytosis by AP and Ela without effect on the bactericidal activity suggests that the P. aeruginosa proteases most probably exert their effect on the cell surface perhaps by proteolytic cleavage of the cell receptors which are necessary for phagocytosis. PMID- 3105249 TI - Expression of MHC class II antigen, interleukin-2 receptor, transferrin receptor and gp 40/80 glycoprotein during different phases of a normal PHA-driven lymphocyte activation in vitro. AB - This study characterizes the temporal profile of MHC class II antigen, interleukin-2 receptor, transferrin receptor and gp 40/80 glycoprotein lymphocyte activation markers in relation to each other during different phases of PHA dependent cellular activation in vitro. Binding of these monoclonal lymphocyte activation-probes was visualized by the avidin-biotin-peroxidase complex method. Maximum PHA-dependent MHC class II antigen expression of 27 +/- 3% was observed on culture day 1, but later no significant differences were observed in MHC class II antigen expression between PHA-driven or culture media-containing control cultures. On the contrary, interleukin-2 receptor (78 +/- 6%) and transferrin receptor (75 +/- 5%) expression reached a maximum on culture day 3, coinciding with a maximum proliferative response. On culture day 5, when 3H-thymidine incorporation was already on the decline, gp 40/80 glycoprotein reached a maximum PHA-dependent expression of 78 +/- 2%, which differed significantly from interleukin-2 receptor (60 +/- 8%, p less than 0.05) and transferrin receptor (51 +/- 8%, p less than 0.01) expression. This study suggests that MHC class II antigen, interleukin-2 receptor, transferrin receptor and gp 40/80 glycoprotein, although all of them are lymphocyte-activation markers, differ as to the chronological sequence of their appearance and disappearance. Their combined use in lymphocyte-activation marker profile assay therefore gives valuable information about the lymphocyte activation state. PMID- 3105250 TI - [Study of "Sebidin A" tablets from the perspective of the effect of accelerated aging on the stability of their components and their antimicrobial activity]. PMID- 3105251 TI - Unaltered 24 h serum PRL levels and PRL response to TRH in contrast to decreased 24 h serum TSH levels and TSH response to TRH in major depressive disorder. AB - The 24 h serum levels of prolactin (PRL) and thyrotropin (TSH) assessed at ten different time points and the PRL and TSH responses to TRH administration (delta PRL, delta TSH) were investigated in 26 inpatients meeting the RDC criteria for an acute major depressive disorder. Fourteen of these patients were reinvestigated in a state of partial or complete remission. Comparison between the patients during both relapse and remission and 23 healthy controls showed no differences in the paramenters reflecting the 24 h PRL levels or delta PRL. However, significantly lower 24 h TSH levels and delta TSH were found in the patient group in the acute phase. Antidepressant medication, sedatives or the outcome of the dexamethasone test did not significantly influence the PRL levels or delta PRL. Both the patient group and the controls revealed normal sleep associated PRL release indicating unaltered serotoninergic and/or dopaminergic neurotransmission regulating the PRL secretion. The present results indicate a selective disturbance affecting the pituitary TSH secretion, and are consistent with our hypothesis that the mechanism behind the decreased TSH levels and the impaired TSH response to TRH in acute major depressive disorder involves a down regulation of the pituitary TRH receptors. PMID- 3105252 TI - Dog erythrocyte rosette-forming lymphocyte: blockage by OKT11 monoclonal antibody. AB - Human peripheral blood mononuclear cells (PBM) were separated into sheep erythrocyte rosette-forming (Es+) and non Es+ cells by the Ficoll-Hypaque gradient sedimentation method. Thirty-eight percent of the Es+ cells formed rosettes with dog erythrocytes and were designated as Es+Ed+ cells. The remaining Es+ cells were designated as Es+Ed- cells. Only a few non Es+ cells formed rosettes with dog erythrocytes. Among Es+Ed+ cells, T4 antigen-positive cells were observed approximately 1.7 times as often as T8 antigen-positive cells, when measured by staining with OKT4 or OKT8 monoclonal antibody. Among Es+Ed- cells, however, T4 and T8 antigen-positive cells were observed in almost equal proportion. Preincubation of PBM with OKT11 monoclonal antibody, but not with OKT4 monoclonal antibody, inhibited the rosette formation with dog as well as sheep erythrocytes. These results indicated that Es+Ed+ cells were a subpopulation of T-cells in which a majority of the cells were T4 antigen positive, and that the binding sites of dog erythrocytes on human T-cells was closely linked with that of sheep erythrocytes. PMID- 3105253 TI - Metaplastic bone formation in a hyperplastic polyp of the stomach: a case report. AB - Metaplastic bony tissue along with hyperplastic mucosal epithelium showing no atypism was detected in biopsy materials from a Yamada type I gastric polyp. The tissue was metaplastic woven bone associated with calcification. Histogenesis of the bone formation is as yet unknown. This is the first reported case of the presence of metaplastic bone accompanied by hyperplastic gastric mucosa so far. PMID- 3105254 TI - Changes in the connective tissue and decrease in the number of mast cells in the testes of men with alcoholic and non-alcoholic cirrhosis. AB - The testicular connective tissue of patients with alcoholic and non-alcoholic cirrhosis was studied by Picrosirius staining for collagen fibres and electron microscopy, and then compared with the connective tissue of normal testes. Under polarized light, the interstitial connective tissue in the testes of patients with alcoholic and non-alcoholic cirrhosis exhibited a green birefringence which did not appear in normal testes, and the orange birefringence characteristic of the tunica propria in the testes of both cirrhotic and normal males was less developed in cirrhosis. This suggests that a connective tissue, consisting of smaller and less ordered collagen fibre bundles than those in the tunica propria is formed in the testicular interstitium of cirrhotic males, and the collagen fibre bundles of the tunica propria are less developed than in normal testes. The appearance of connective tissue was associated with a decrease in the number of mast cells in the testes of cirrhotic males suggesting the involvement of mast cells in the synthesis, packing, and organization of collagen fibres. The cause of the decrease in mast cell numbers may be related to hormone alterations, in particular testosterone deficiency. PMID- 3105256 TI - Changes of free histones in chick testicular and ovarian cells after embryonic and/or neonatal treatment with diethylstilbestrol (DES) or allyloestrenol (AE). AB - DES and AE when injected into the yolk sac of chick embryos on the 9th day of incubation decreased the neonatal weight of the testis and the PMB-reaction of spermatogonia whereas they increased the neonatal weight and granulosa cell PMB reaction of the ovary. In the ovary, embryonic treatment increased the efficiency of post-hatching hormone treatments. PMID- 3105255 TI - Intraocular invasion of recurrent epibulbar malignant melanoma. AB - A case of a recurrent epibulbar naevus is presented; it underwent malignant transformation and subsequently invaded the eyeball. The tumour histologically was a predominantly epitheloid cell melanoma containing numerous histiocytes and degenerated tumour cells. Electron microscopy revealed rare special structures, e.g. annulated lamellae, tubuloreticular structures, pseudocrystals in huge mitochondria. Besides, invasion of tumour cells into a capillary could be shown. PMID- 3105257 TI - Morphological characteristics of incrustates of intrauterine contraceptive devices. AB - The morphology of incrustates formed on intrauterine contraceptive devices (IUD) is described. It is demonstrated that due to manufacturing technology some IUDs have long, parallel excavations serving as sites for incrustate formation. A regional difference of incrustation on the different parts of IUD has also been observed. Electron microscopy was carried out in tissue fragments attached to removed IUDs. Alterations correspond to acute or chronic inflammation. Incrustate on the surface of IUD appears to have a primary role in induction of the process. PMID- 3105258 TI - Functional morphology of the adrenal cortex in newborns. I. Morphometric study. AB - Adrenal cortex of fetuses from abortion and newborns as well as 3 anencephalic monsters between 16 and 40 weeks gestational age was investigated. In order to follow the activity of adrenal cortex the volumes of nuclei and of cells were determined by means of morphometry in both the fetal and the definitive zones. The volume of cells showed correlation with gestational age only in the definitive zone. The absence of significant changes in the other (fetal) zone raises the possibility that dysfunction of the adrenal cortex and the consecutive insufficient adaptation could be made responsible for premature birth and perinatal mortality in the cases reported here. PMID- 3105259 TI - Functional morphology of the adrenal cortex in newborns. II. Morphological and biochemical analysis of lipid accumulation. AB - The adrenal cortex of 32 newborns and of 3 anencephalic monsters of 16 to 40 weeks' gestational age was examined. Functional activity of the adrenal cortex was followed by analysis of the zonal distribution of lipids and by measurement of the total cholesterol content. The cholesterol content ranged between 0.15 and 0.85 mg/100 g. Cholesterol accumulation was highest in the anencephalic monsters. The relative cholesterol content failed to show any correlation with gestational age. When compared with the biochemical determination of cholesterol content, morphological investigation of lipid accumulation proved to be superior and to be a suitable method for estimation of zonal maturity even in individual cases. PMID- 3105260 TI - Free histones in the cells of the rat uterus after neonatal treatment with diethylstilbestrol or allylestrenol. AB - Neonatal diethylstilbestrol and allylestrenol treatments resulted in a prompt release of free histones that could be demonstrated histochemically by the phosphomolybdic-acid-benzidine reaction. This effect could not be observed in the uterus of 6-10-week old rats but reappeared between 11-14 weeks in the myometrium and uterine epithelium without any repeated treatment. This may be due to the increased production of endogenous steroids. The finding suggest caution when applying steroids to pregnants and neonates. PMID- 3105262 TI - Fine structure of the neuromuscular junction in the small intestine of a teleostean fish: tench (Tinca tinca L.). AB - Innervation of the midgut musculature has been studied in the tench (Tinca tinca) by light and electron microscopic methods. Smooth and striated muscle layers of the tunica muscularis of the gut are innervated by the same nerve bundles. Thick nerve bundles are found in the connective tissue between the two muscle layers projecting branches into both the smooth and striated muscle layers. The nerve fibres are varicose, the varicosities contain various vesicle populations. Some of these comprise small clear vesicles (measuring 40 nm in diameter), and a few dense-core vesicles (120 nm in diameter), while in others the amount of dense core vesicles is higher; furthermore there are varicosities containing granules of peptidergic character measuring 200 nm in diameter. Nerve fibres often form neuropil in which synapses have not been observed. Axon terminals establish parallel membrane contacts with the muscle cells without synaptic specialization in the smooth muscle layer. Innervation of the striated muscle layer seems to be poor. Motor end-plates could not be found on the muscle fibres of the midgut, while these are common in the oesophagus, where the occurrence of striated muscle fibres is dominant. PMID- 3105261 TI - Morphometric studies of development of the rat testis under physiological conditions and after CdCl2 poisoning. AB - The morphometrical data of the rat testis were studied between the 1st day and 1.5 year of life under physiological conditions and after intraperitoneal injection of a single dose of cadmium chloride (1.5 mg CdCl2/kg body weight). Under physiological conditions three main period of development occur: between the 1st and 30th day of life, between the 30th and 45th day of life, and after the 45th day of life. The greatest changes after the injection of cadmium were noticed in the period between the 15th and 30th day of life. The periphery of the organ was the first to suffer severe damage. PMID- 3105263 TI - Late effects of embryonic allylestrenol treatment in chicken. AB - Allylestrenol when applied to chick embryos on the 9th day of incubation or on the 9th day of incubation and at hatching brought about a severe purulent inflammation of the oviduct at 6 weeks of age in 50% of the animals. Treatment at hatching only had no effect whatsoever. The findings suggest that allylestrenol must be applied with caution during pregnancy. PMID- 3105264 TI - Alterations in red blood cell morphology during a 500 metre dive. AB - Following compression to 500 m in a simulated chamber dive, the blood samples of the six divers were all found to contain several types of non-discoid erythrocytes. Compression to this depth induced a pressure stress and sensitisation in a proportion of each divers' erythrocyte population. Long in vitro decompression procedures further stressed these red cells and resulted in additional morphological changes. The formation of stomatocytes was increased by an acidic-buffered fixative, conversely, an alkaline medium caused echinocytosis. Cell counts of each morphological cell type showed that as echinocyte stage III & IV numbers were reduced a simultaneous decrease in mean haemoglobin concentration occurred. Decompressions of blood samples for routine haematology should be at a rate of 3 m/min so as to be completed within four hours from venesection. Hyperbaric exposure time explicitly influence these red cell anomalies and development of a subclinical anaemia. PMID- 3105265 TI - Applicability of the anaerobic threshold in patients with previous myocardial infarction. PMID- 3105266 TI - Effect of Norplant on mothers and infants in the postpartum period. AB - To evaluate the effect of Norplant on lactation and the growth of the infant, a comparative study on lactating women using a cohort approach has been carried out in Klinik Raden Saleh, Department of Obstetrics and Gynaecology, University of Indonesia and Dr Cipto Mangunkusumo General Hospital, Jakarta. The recruitment of the study group took place between 1 November 1983 and 31 August 1984. The inclusion criteria, among others, were age 18-40 years, full term gestation, spontaneous delivery, 4-6 weeks after delivery and plans to breastfeed for at least 6 months. The study group consisted of 60 Norplant acceptors, while the control group consisted of 60 Cu-7IUD acceptors. The subjects had a free choice in deciding which form of fertility regulation they preferred. After 6 months of observation the following conclusions were drawn: Norplant use did not have any effect on maternal body weight, hemoglobin concentration or breastmilk production in comparison with IUD use. The development of infants breastfed by Norplant acceptors was not delayed compared to that of infants breastfed by IUD acceptors. PMID- 3105267 TI - Renal proximal tubular brush-border membrane transport of phosphate with acute acidosis. PMID- 3105268 TI - Immune cells and bone resorption. PMID- 3105270 TI - Confirming long-stay status. AB - This paper discusses an assessment procedure for the formal identification of patients requiring long-stay geriatric care. It was introduced immediately prior to the reorganization of geriatric in-patient care at St Pancras Hospital which saw the abolition of mixed wards of acute, rehabilitation, and long-stay patients and their replacement by six specialized wards, three of which are long-stay wards accommodating 51 patients. The formal assessment and referral for long-stay care is itself one outcome of deliberations made by a multidisciplinary panel formed a few months before the hospital reorganization to examine the kind of care and environment that might best enable the long-stay elderly to enjoy, within the limits of their disabilities, as dignified and worthwhile lives as possible. The paper begins by outlining the reasons why an assessment procedure came to be seen as a necessary and important element in the new system of continuing care of geriatric patients. This is followed by a brief consideration of how the procedure operates. An example of the assessment form is included. PMID- 3105269 TI - Genetics of lactose digestion in humans. PMID- 3105271 TI - Prescribing patterns observed in registered nursing homes and long-stay geriatric wards. AB - Details of medication prescribed to 400 elderly patients in 18 registered nursing homes and 233 patients in 11 long-stay geriatric wards were obtained. Excluding laxatives, there was a mean of 2.15 medications prescribed for the long-stay patients, compared to 2.62 items for the nursing-home population. There was apparent over-prescribing of certain drugs within the nursing-home population. PMID- 3105272 TI - [Studies on 5-FU concentration in serum and bladder tumor tissue after oral administration of UFT]. AB - The concentration of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT), 5-fluorouracil (5 FU) and uracil in blood, the bladder tumor tissue and the bladder mucosa after oral administration of 600 mg per day of UFT for 7 consecutive days was examined in 10 cases of bladder tumors. The concentration of FT and uracil in the tumor tissue did not significantly increase as compared with that in the blood and the bladder mucosa. However, the concentration of 5-FU in the tumor tissue remarkably increased and was 10.7 and 4 times as much as that in the blood and the bladder mucosa, respectively. These results show that administration of UFT meaningfully increases the 5-FU content in bladder tumors and enhances the antitumor activity. PMID- 3105273 TI - [Epidemiological and therapeutic studies on gonorrheal infections--clinical efficacy of T-2588. (Sapporo Clinical Research Group for STD)]. AB - T-2588, a new oral cephalosporin antibiotic, for gonorrheal infections, was administered to 146 patients with gonorrheal infection cases (140 urethritis cases in males, 6 cervicitis cases in females). Twenty three strains (20.9%) out of 110 clinically isolated gonococci were PPNG. The MICs of T-2588 for the clinically isolated gonococci strains showed a distribution peak at 0.025 microgram/ml and ranged between 0.0125 microgram/ml to 0.1 microgram/ml when an inoculum size of 10(6)/CFU/ml was used. The distribution of MICs of PPNG also showed a peak at 0.025 microgram/ml and the maximum MIC was 0.2 microgram/ml, which is one dilution tube higher than the maximum MIC of non-PPNG. The rate of complication by Chlamydia trachomatis was 20.9% in male and 33.3% in female. At the dose of 400 mg given 2 times a day, the efficacy rate for the males on the 3rd and 7th day was 90.5% (efficacy rate against PPNG, 73.3%) and 95.3% (80.0%), respectively. At the dose of 300 mg given 3 times a day, it was 93.3% and 100%, respectively, and at the dose of 600 mg given 3 times a day, it was 100% and 100%, respectively. Therefore, the administration of T-2588 3 times a day resulted in a higher efficacy rate than that given 2 times a day. This effect was extremely marked in the case of patients with PPNG. The best clinical results were obtained at a daily dose of 600 mg t.i.d. Although the female patients were few, in number and no conclusion can be drawn, the best results were obtained with a daily dose of 600 mg t.i.d. (100%). There were three mild side effects (1.7%), which could not be attributed to the administration of T-2588 in the present study. In conclusion, T-2588 can be to be expected sufficiently clinically effective against gonorrheal infections, including PPNG, at a daily dose of 600 mg t.i.d. for 3 days. PMID- 3105274 TI - Observations of toxic blue-green algae (Cyanobacteria) in some Scandinavian lakes. PMID- 3105275 TI - The role of dural anomalies in vein of Galen aneurysms: report of six cases and review of the literature. AB - It is proposed that the vein of Galen aneurysm represents a venous ectasia secondary to an increased flow (usually caused by a deep-seated arteriovenous shunt draining either directly into the vein of Galen aneurysm or into a tributary of the vein of Galen) associated with obstruction of a dural sinus distal to the aneurysm. The closer the venous obstruction is to the vein of Galen, the better the chances are of developing obstructive (noncommunicating) hydrocephalus and the more likely it is that the venous drainage from the rest of the brain will be unaffected. The farther the venous obstruction is from the vein of Galen aneurysm, the better the chances are of developing a communicating type of hydrocephalus. The development of cardiac failure is related to the magnitude of the arteriovenous shunt. Brain damage, seizures, and hemorrhage may be related to the retrograde venous engorgement, causing impaired drainage of the healthy brain. Careful attention should be paid to the venous drainage characteristics of the lesion because the types of dural venous obstructions and anomalies vary from case to case. The term "vein of Galen aneurysm" should be abandoned in favor of the term "vein of Galen ectasia." PMID- 3105276 TI - Cerebral hemodynamics in arteriovenous malformations: evaluation by single-photon emission CT. AB - Cerebral hemodynamics in six patients with supratentorial arteriovenous malformations (AVMs) were studied by using single-photon emission CT with three types of radioactive isotopes: N-isopropyl-p-[123I] iodoamphetamine, 81mKr, and 99mTc-RBC in order to determine the local cerebral blood flow and blood volume associated with these malformations. The AVMs were shown to have high flow while other areas of the brain, including the contralateral hemisphere, had variable areas of diminished perfusion. There was increased blood volume in the regions of AVMs, and poor but evenly distributed blood volume in the other regions. CO2 reactivity during hypocapnia was preserved throughout the brain except for the region of the AVMs. In large AVMs, the ischemic state surrounding the nidus was considered to be caused mainly by the cerebral steal phenomenon. PMID- 3105277 TI - The vascular territories in the cerebellum and brainstem: CT and MR study. AB - More than 100 CT and 15 MR studies of infarcts in the cerebellum and brainstem were reviewed to define the most typical distribution of infarcts in the different vascular territories. Posterior inferior cerebellar artery and anterior inferior cerebellar artery territories are variable in size and are in a sort of equilibrium with each other. The posterior inferior cerebellar artery territory in transverse sections reveals a characteristic posterior crescent caused by its cranial posterior extension. The anterior inferior cerebellar artery territory may be limited to the lateral inferior pontine and floccular regions but usually extends over the whole petrosal surface of the cerebellum up to the lateral angle. Superior cerebellar artery territory is the most extensive territory and includes the largest part of the deep white matter. Infarcts in a single-branch distribution, vermian or hemispheric, have a characteristic sagittal or oblique orientation. Watershed cerebellar infarcts can also be recognized. In the brainstem, paramedian, lateral, and dorsal penetrating arteries have characteristic distributions at the medullary, pontine, and mesencephalic levels. With MR, lateral medullary infarcts can be demonstrated. Paramedian penetrating arteries are paired, and symmetric and small infarcts at medullary and pontine levels are sharply delimited on the midline. At the mesencephalic level, infarcts in this distribution usually involve all the arteries originating from the tip of the basilar artery and from the precommunicating segment of the posterior cerebral arteries, resulting in a central mesencephalic infarct with bilateral upward extension in the thalami. The different vascular territories in the cerebellum and in the brainstem are illustrated in schematic drawings in transverse, coronal, and sagittal planes. Knowledge of the vascular territories gained by the multiplanar capabilities of MR, and knowledge of the CT patterns of enhancement and evolution, will improve recognition and definition of infarcts. PMID- 3105278 TI - Cerebral angiography in brainstem revascularization. AB - Surgical management of patients with vertebrobasilar insufficiency has been developed within the past decade. Cerebral angiography plays a crucial role in identifying potential surgical candidates and in directing the surgical approach. Fifty-two patients underwent brainstem revascularization procedures at Henry Ford Hospital between November 1979 and August 1985. Twelve occipital artery to anterior inferior cerebellar artery bypasses, five occipital artery to posterior inferior cerebellar artery bypasses, four intracranial vertebral endarterectomies, 29 superficial temporal to superior cerebellar artery bypasses, and two superficial temporal to posterior cerebral artery bypasses were performed. The preoperative angiograms in these patients were analyzed to illustrate how angiographic localization of vascular disease directs the surgical approach. We report the results of postoperative angiograms. Technical features of the various surgical procedures, the role of the neuroradiologist, and several features of the angiographic technique used with these patients are described. PMID- 3105279 TI - CT of subinsular infarction and ischemia. AB - A number of CT head scans, covering a 2-year period and showing a variety of distinct curvilinear subinsular lucent lesions, were collected and reviewed. Variations in extent of involvement, tendency toward bilateral symmetry, and clinical background allowed the lesions to be grouped into four general patterns, most of which, to our knowledge, have not been specifically described in the radiologic literature. This project was undertaken first to bring to the attention of those involved in interpretation of cranial CT images several patterns of injury they may not heretofore have been aware of and second to attempt to derive a specific etiology for each of the patterns described. Pattern 1, which appears as a distinct curvilinear lesion (sometimes cystic) apparently limited to the lateral aspect of the putamen, is thought to represent the residua of previous lateral striatal hemorrhage. Pattern 2, occurring in a markedly younger age group appears as relatively symmetrical bilateral subinsular lucencies, which in one case completely resolved. A specific etiology for this pattern remains uncertain. Acute demyelination, either secondary to a variant of anoxic leukoencephalopathy or to a limited form of diffuse encephalomyelitis, is postulated. A third pattern, which extends from generalized deep frontal white matter lucency across the anterior limb of the internal capsule and tapering posteriorly in the subinsular area is thought to be on the basis of chronic ischemia similar to subcortical arteriosclerotic encephalopathy. The fourth pattern, occurring as a broad band of lucency extending from the frontal horn of the lateral ventricle and also tapering posteriorly is due to relatively proximal occlusion of the lateral lenticulostriate arteries. PMID- 3105280 TI - CT of ischemic infarctions in the territory of the anterior choroidal artery: a review of 28 cases. AB - The purpose of the present study was to examine the incidence, causal factors, and anatomic localizations of infarction in the territory of the anterior choroidal artery. We studied 28 patients who had CT evidence of infarction in this territory. The affected structures taken into consideration were the posterior limb of the internal capsule, the retrolenticular portion of the internal capsule, the internal portion of the globus pallidus, and the lateral thalamus. Three conclusions are drawn: that ischemic infarcts in the territory of the anterior choroidal artery are rare, representing 2.9% of all cerebral ischemic lesions in our material; that the incidence of a possible embolic origin is significant; and that the posterior two-thirds of the posterior limb of the internal capsule and the retrolenticular segment are the more frequently affected structures, and conversely, that the medial pallidus and the thalamus are less often involved. PMID- 3105281 TI - Saccular aneurysms in basilar artery fenestration. AB - Of 59 cases of vertebrobasilar junction aneurysms diagnosed and treated from January 1977 to April 1986, 21 (35.5%) saccular aneurysms arose in a fenestration of the proximal basilar artery. Defects of the media at the junctures of the fenestrated segments, as well as the possible presence of turbulent flow at the vertebrobasilar junction, may explain the high incidence of vertebrobasilar aneurysms associated with proximal basilar artery fenestration. PMID- 3105282 TI - Use of an open-ended guidewire: steerable microguidewire assembly system in surgical neuroangiographic procedures. PMID- 3105283 TI - Internuclear ophthalmoplegia: MR-anatomic correlation. AB - Internuclear ophthalmoplegia is a gaze disorder characterized by impaired adduction on the side of a lesion involving the medial longitudinal fasciculus with dissociated nystagmus of the abducting eye. Eleven patients with internuclear ophthalmoplegia (nine with clinical multiple sclerosis, two with clinical infarction) underwent MR imaging with spin-echo techniques on a 1.5-T system. Nine patients also had CT. MR showed focal or nodular areas of high signal intensity on T2-weighted images in the region of the medial longitudinal fasciculus in 10 of 11 patients. In one of four patients with internuclear ophthalmoplegia who had MR after intravenous gadolinium-DTPA, an enhancing ring lesion was seen in the region of the medial longitudinal fasciculus on short TR/TE images, indicating active blood-brain-barrier disruption, which correlated with this patient's recent-onset internuclear ophthalmoplegia. CT failed to show the lesions in all nine patients examined. This report demonstrates the superiority of MR in evaluating gaze disorders attributable to brainstem dysfunction, such as internuclear ophthalmoplegia, and correlates MR findings with the relevant neuroanatomy of the medial longitudinal fasciculus. PMID- 3105284 TI - Dynamic MR imaging: a further possibility for characterizing CNS lesions. AB - To improve the specificity of MR imaging, 45 patients with different lesions in the CNS were studied with gadolinium-DTPA from June to December 1985. With a dosage of 0.2 ml/kg body weight, no adverse effects were seen. Seventeen of these patients were also studied with dynamic MR imaging, using a spin-echo sequence of TR = 100 msec and TE = 30 msec and a display matrix of 128(2). Four parameters were determined and compared with histologic findings: the time to peak of signal intensity, the ascent to peak of signal intensity, the height of peak of signal intensity, and the percentage of peak of signal intensity at the end of measurement. In this small series, arteriovenous malformations had a short time to peak and a steep ascent to peak as compared with tumors. Gliomas had a slow ascent to peak and usually a longer time to peak as compared with tumors of mesodermal origin. Paragliomas according to Zulch's classification had a steeper ascent to peak than gliomas. Dynamic MR with gadolinium-DTPA may lead to further information about lesions in the CNS, as the ascent to peak parameter seems helpful in discriminating among different lesions. PMID- 3105285 TI - A nonplanimetric technique for measuring fluid volumes using MR imaging--phantom results. PMID- 3105286 TI - CT features of early Listeria monocytogenes cerebritis. AB - Listeria monocytogenes is a relatively uncommon pathogen affecting infants or adults with predisposing conditions, such as cirrhosis, diabetes mellitus, autoimmune disease, renal transplants, and solid and lymphoreticular malignancies. Cerebral parenchymal involvement is rare and consists of focal cerebritis, which may progress to abscess formation. This article presents three cases of early Listeria monocytogenes cerebritis, two of which demonstrated ill defined superficial areas of low attenuation with curvilinear gyral enhancement and one of which demonstrated a deep, low-attenuation lesion with faint surrounding enhancement. Although these findings are nonspecific, their early recognition in the proper clinical setting may help institute early antibiotic therapy, which appears to be successful without surgical intervention. PMID- 3105287 TI - Periventricular cavitations in the first week of life. AB - Eleven infants were encountered (nine premature, two term) in whom well-defined small periventricular cavitations were found by sonography in the first week of life. The sonographic findings bore remarkable similarity to subependymal pseudocysts in neonates previously described in autopsy specimens. The cavitations, which were identified predominantly along the superolateral aspects of the lateral ventricles, did not evolve in the manner of postnatally acquired periventricular leukomalacia. The location of the cavitations differed from the site of previously reported lesions of posthemorrhagic and postinfectious germinolysis along the medial aspect of the caudothalamic groove. Neurosonologists and neonatologists should be alerted to this finding and encouraged to follow these infants as a separate group to learn whether neurodevelopmental sequelae occur in these children. PMID- 3105288 TI - MR of postoperative syringomyelia. AB - Twenty-seven MR scans of 20 patients surgically treated for syringomyelia were reviewed. Thirteen patients had syringomyelia associated with the Chiari I malformation, four cases were posttraumatic, and three were idiopathic. The operations performed included syringosubarachnoid and syringoperitoneal shunts, myelotomies, and foramen magnum decompressions. Three of the foramen magnum decompressions had associated posterior fossa duroplasties, two had fourth ventricle-to-subarachnoid shunts, and two had plugging at the obex. On 20 scans of patients in whom the syrinx cavity had been shunted, the shunt catheter was seen in 15 (75%). When adequately treated by shunting, syringes are completely collapsed and show no flow void. Nine patients were treated by foramen magnum decompression; all were well seen by MR. Three of these patients had a poor clinical result; these were the only patients in whom CSF was not seen between the foramen magnum and the neural structures of the posterior fossa on any images. The proposed mechanisms of syrinx formation and extension are discussed and related to the surgical procedures used to treat syringomyelia. PMID- 3105290 TI - The optic syrinx: cavernous degeneration of the optic nerve demonstrated by iopamidol optic neurography. AB - Cavernous degeneration of the optic nerve has been described predominantly in association with long-standing glaucoma, although less frequently it has been reported in other, disparate disease processes. The only descriptions to date have been in pathologic specimens in vitro. This is the first report to describe syrinx formation of the optic nerves in vivo in two patients with nonglaucomatous conditions affecting the optic nerves. PMID- 3105289 TI - Osmotic disruption of the blood-ocular barriers. PMID- 3105291 TI - Imaging of rhabdomyosarcomas of the head and neck. AB - Rhabdomyosarcoma (RMS) is the most common childhood malignancy of the head and neck. The Intergroup Rhabdomyosarcoma Study now divides head and neck RMS into three categories by site of origin: orbital, parameningeal (middle ear, paranasal sinuses, and nasopharynx), and all other head and neck sites. CT is clinically applicable in the diagnosis of RMS of the head and neck, in treatment planning, and in the follow-up of patients with these tumors. Specific areas of applicability include determination of the presence/absence of intracranial and meningeal involvement, definition of tumor extent to guide radiation therapy planning, and demonstration of tumor regression or recurrence during and after treatment. CT has played an important role in the dramatically improved prognosis seen in RMS over the last 10 years. The role of MR in evaluating these patients is not yet defined, but it has promise because of the ease of obtaining multiple projections and the avoidance of ionizing radiation. PMID- 3105292 TI - Cerebellopontine angle lymphoma. PMID- 3105293 TI - MR in the diagnosis of colloid cysts of the third ventricle. PMID- 3105294 TI - Cerebral varix associated with a venous angioma. PMID- 3105295 TI - Lipomeningomyelocystocele. PMID- 3105296 TI - CT evaluation of plastic intraocular foreign bodies. PMID- 3105297 TI - Balloon embolization in a carotid-cavernous fistula in fibromuscular dysplasia. PMID- 3105298 TI - MR in diffuse angiomatosis. PMID- 3105299 TI - Thoracic spinal meningioma associated with hydrocephalic dementia. PMID- 3105300 TI - Compressive meningeal hypertrophy in mucopolysaccharidosis. PMID- 3105301 TI - Dilemmas of streptococcal pharyngitis. AB - Although the Group A beta-hemolytic streptococcus is the most common cause of acute bacterial pharyngitis in childhood, the clinical diagnosis is often not straightforward and throat cultures are advisable. To avoid unnecessary antibiotics, treatment should be delayed until culture results are available. Patients with negative cultures should discontinue any antibiotics already started on clinical grounds. Positive cultures may represent a carrier state, which can be identified by serologic studies. PMID- 3105302 TI - Capillary gas chromatography of cotton dusts associated with human pulmonary function studies. AB - The effects of geographical area of growth and cotton variety on pulmonary activity have been evaluated through human volunteer exposure studies conducted by NIOSH and USDA at the Cotton Quality Research Station, Clemson, S.C. These studies demonstrate that carding California cottons releases dust with less human pulmonary activity than dust released from the corresponding Mississippi cottons. Dust released from Texas cottons grown in 1982 was considerably less active than the dust from Texas cottons grown in 1983. Distinct differences in the chemical compositions of the Mississippi, Texas, and California cardroom dusts were found. Aqueous extracts of the dusts were freeze-dried and then derivatized. Capillary gas chromatography revealed that the California dust extracts and the 1982 Texas dust extract were characterized by relatively higher levels of malic acid, whereas the Mississippi dust extracts and the 1983 Texas dust extracts were characterized by relatively higher mannitol levels. PMID- 3105303 TI - Recombinant tissue plasminogen activator (rt-PA): is it the thrombolytic agent of choice for an evolving acute myocardial infarction? PMID- 3105304 TI - Enteral feeding in very-low-birth-weight infants. A comparison of two nasogastric methods. AB - Nutritional benefits and feeding-related complications were prospectively compared in 53 preterm very-low-birth-weight infants receiving isoenergetic feeding by either the continuous nasogastric (n = 30) or intermittent nasogastric (n = 23) route. Stepwise regression techniques were used to develop models relating feeding-associated factors. Feeding method significantly affected weight gain in infants 1000 to 1249 g birth weight with continuous nasogastric feeding associated with an additional weight gain of 3.6 to 6.1 g/kg/d. No effects of feeding method on changes in occipitofrontal circumference, triceps skin-fold thickness, bilirubin values, or total protein values were demonstrable. There were few major differences between feeding groups on measures of feeding complications. Continuous nasogastric feeding was fairly well tolerated and resulted in improved weight gain when compared with intermittent nasogastric feeding in preterm infants 1000 to 1249 g birth weight. PMID- 3105305 TI - Anti-platelet and anti-DNA IgM in Waldenstrom macroglobulinemia and ITP. AB - We describe a monoclonal IgM that was purified from the serum of a patient with Waldenstrom macroglobulinemia and thrombocytopenia. The binding and idiotypic characteristics of the patient's macroglobulin were similar to those of a human monoclonal IgM secreted by a hybridoma established from peripheral blood lymphocytes of a patient with systemic lupus erythematosus and immune thrombocytopenia. In the absence of other causes for thrombocytopenia in this patient, our results suggest an autoimmune mechanism for destruction of platelets by the monoclonal IgM. This is the first report of a Waldenstrom macroglobulinemia with anti-platelet activity of monoclonal IgM. Although the study involves a single patient, the results suggest that there may be a common origin for autoantibodies in autoimmune diseases and monoclonal immunoglobulins having autoantibody activity in monoclonal gammopathies. PMID- 3105306 TI - An acquired inhibitor to factor VIIIC in a non-hemophiliac: twenty years of observation and characterization. AB - A non-hemophilic patient with an acquired inhibitor to factor VIIIC was initially diagnosed in this laboratory 20 years ago at age 63. Following its initial appearance in 1963, the inhibitor was detectable on two other occasions. We believe that this is the longest duration such an inhibitor has persisted. No sample remained from his initial admission; however, samples were available from the last 8 years of his life for retrospective study. Preparative isofocusing, affinity chromatography, and immunoglobulin subtyping were used to determine the similarities and/or differences in the inhibitor over these 8 years. The following similarities and differences were observed in both the 1975 and 1983 plasmas. Isofocusing showed that both plasmas contained peaks of inhibitory activity with pIs of 7.25, 8.26, and 8.88; the 1975 sample in addition contained two peaks with pIs of 7.77 and 9.45, whereas two other peaks with pIs of 7.64 and 7.85 were found in the 1983 sample. For the final characterization, each isofocused inhibitory peak was eluted from Protein A Sepharose and incubated with antisera to determine the immunoglobulin subtype. Each peak consisted of mixtures of IgG1 and IgG4 with both kappa and lambda light chains. It was concluded that the inhibitor was polyclonal, based on the presence of inhibitory peaks with different pIs and immunoglobulin subtypes. These findings support the conclusion that the development of and changes in the inhibitor was a dynamic process with some inhibitors (antibodies) persisting, while at the same time others with different characteristics were being formed. PMID- 3105307 TI - Computerized order calculation and label generation for neonatal parenteral nutrient solutions. PMID- 3105308 TI - More on production of carbon dioxide gas after reconstitution of ceftazidime. PMID- 3105309 TI - Immunoglobulin gene rearrangements in adult non-Hodgkin's lymphoma. AB - Southern blotting was employed to analyze the immunoglobulin heavy and light chain genes and the gene for the T cell receptor beta chain in genomic DNA derived from the tumor specimens of 120 adults with pathologically classified and immunotyped non-Hodgkin's lymphoma and B cell chronic lymphocytic leukemia. In a consecutive series of 100 patients, one or two rearranged heavy chain genes could be detected in each of the 80 samples expressing clonal surface immunoglobulin. The kappa gene was rearranged in 70 percent of kappa-bearing tumors and in 23 percent of lambda-bearing specimens. Furthermore, a rearranged immunoglobulin gene was also observed in 21 of 29 lymphomas (nine from the consecutive series and 20 selected for surface immunoglobulin-negative status) in which B cell lineage was in doubt because of absent clonal surface immunoglobulin. These findings indicate that most cases of lymphoma and lymphocytic leukemia in adults are of B cell lineage, even when phenotypic evidence is inconclusive. The exceptional cases (only 3 percent in the consecutive series) were of either follicular lymphoma or diffuse large cell (histiocytic) lymphoma subtype; the lineage in cases of diffuse lymphocytic lymphoma or chronic lymphocytic leukemia was never in doubt. Although the convenience of surface marker analysis assures its continuing clinical application, gene study resolves indeterminate cases and extends the understanding of the pathogenesis of lymphoproliferative disease. PMID- 3105310 TI - Beneficial effects of dietary carbohydrate restriction in chronic cor pulmonale. AB - To explore the effects of moderate and severe reductions in carbohydrate intake on abnormal pulmonary physiology in chronic hypercapneic respiratory failure, spirometric, metabolic, arterial blood gas tension, and oximetric studies were carried out in eight patients who took, in random order daily for a week, either 50 g or 200 g of carbohydrate in an isocaloric diet. At the end of a week's daily intake of an isocaloric diet containing 200 g of carbohydrate, all patients experienced a subjective improvement; the mean body weight was 55.5 +/- 15.4 kg (1 SD) compared with 56.0 +/- 16.0 kg during the control dietary period, the arterial carbon dioxide tension decreased from a mean of 56.9 +/- 6.7 to 50.9 +/- 6.2 mm Hg (p less than 0.005), and the arterial oxygen tension increased from a mean of 50.6 +/- 7.3 to 62.0 +/- 14.5 mm Hg (p less than 0.02). After a week's intake of 50 g of carbohydrate in an isocaloric diet, the body weight and arterial oxygen tension did not change significantly, but the arterial carbon dioxide tension decreased still further to 48.0 +/- 7.8 mm Hg (p less than 0.05). Mouth pressure at 100 msec after the start of inspiration, as a measure of respiratory center output, was significantly higher during both the low carbohydrate intakes compared with the control dietary period. The spirometric data, ventilation-perfusion distribution measurements, oxygen consumption, and carbon dioxide production did not change significantly during various dietary periods. It is concluded that, under these short-term, hospital-controlled conditions, a reduction in the carbohydrate intake to 200 g a day improves the general well-being of patients with chronic hypercapneic respiratory failure, increases arterial oxygen tension, and decreases arterial carbon dioxide tension. A further reduction in the carbohydrate intake to 50 g a day provides further beneficial effects, and such a diet may be used in patients with intractable respiratory failure. PMID- 3105311 TI - Proteoglycans and hypertension: III: Aorta proteoglycans in Dahl salt-sensitive hypertensive rats. AB - The vascular proteoglycans probably have an important influence on the biomechanical properties of blood vessels and, therefore, may play a role in the development or maintenance of hypertension. In the aorta of the spontaneously hypertensive rat, the authors previously observed an increased content of chondroitin sulfate, an increased incorporation of [35S]sulfate into proteoglycans, and qualitative alterations in the [35S]polysaccharides compared to the normotensive Wistar Kyoto rat. To determine if these differences were related to hypertension or to strain variations, normotensive and hypertensive Dahl S rats were studied. There was a significant elevation (70%) in the aorta content of chondroitin sulfate, whereas the dermatan sulfate and hyaluronic acid contents were similar in the two groups. The in vitro incorporation of [35S]sulfate was increased 2.6-fold in the hypertensive animals. No differences between the two groups were observed with respect to the gel chromatographic profiles of the [35S]proteoglycans or the charge density of the [35S]glycosaminoglycans, as assessed by ion exchange chromatography. It was concluded that the increase in chondroitin sulfate and [35S]sulfate incorporation into proteoglycans occurred as a result of hypertension, regardless of genetic factors. PMID- 3105313 TI - Tissue plasminogen activator: from molecular biology to myocardial infarction. AB - The recent development of recombinant tissue plasminogen activator as a therapeutic agent during acute myocardial infarction is one of the most lucid examples of the potential impact of recombinant DNA technology in clinical medicine. This remarkable achievement would not have been possible without several key discoveries in molecular biology and clinical cardiology and exemplifies the synergistic relationship between basic and clinical research. This article chronicles this journey from molecular biology to myocardial infarction. PMID- 3105312 TI - Thrombolytic therapy for patients with acute myocardial infarction. AB - Thrombolytic therapy is becoming an important addition to the care of patients with transmural (Q-wave) myocardial infarction. In this review, the authors analyze the mechanisms of effect and thrombolytic capabilities of several currently used thrombolytic interventions and review the influence of reperfusion in reducing mortality and protecting segmental ventricular function in animal models and patients. The problems related to thrombolytic therapy also are discussed and patient subgroups most likely to benefit from thrombolytic therapy identified. Finally, the authors speculate concerning future alterations in thrombolytic agents and additions to thrombolytic therapy as they might be usefully applied in the care of patients with acute transmural myocardial infarcts. PMID- 3105314 TI - Cat-eye syndrome with different marker chromosomes in a mother and daughter. AB - Except for atypical eye findings in the daughter, a mother and daughter with bisatellited marker chromosomes had abnormalities consistent with cat-eye syndrome. The mother's marker chromosome (mar number 1) is derived from one 22 and another acrocentric, possibly also a 22; the daughter's marker (mar number 2) may be an iso-dicentric, inv-dup (22) derivative of mar number 1. The mother has a tertiary trisomy translocation chromosome composed of at least one and perhaps two copies of 22pter----q11.2, whereas the daughter clearly has a secondary trisomy 22pter----q11.2 isochromosome, confirming this region as a cause of cat eye syndrome. Results of hybridization using a unique sequence probe localized to 22q11 are consistent with the interpretation that both ends of both marker chromosomes are derived from 22. PMID- 3105315 TI - Vertical transmission of the neurofibromatosis/Noonan syndrome. AB - We are reporting on a boy and his mother with neurofibromatosis and manifestations of Noonan syndrome, including short stature, ptosis, midface hypoplasia, and short neck. Developmental delay was noted in the son, and the mother was noted to have a heart murmur. There was a family history of cafe-au lait spots, and photographs of several of these relatives showed a facial appearance suggesting Noonan syndrome. The presence of neurofibromatosis associated with Noonan syndrome manifestations in our related patients suggests presence of a unique disorder sharing characteristics of both conditions. PMID- 3105316 TI - Evidence that the "neurofibromatosis-Noonan syndrome" is a variant of von Recklinghausen neurofibromatosis. PMID- 3105317 TI - Recombination between the factor VIII gene and the DXS52 locus gives the most probable genetic order as centromere-fra(X)-DXS15-DXS52-F8C-telomere. AB - The linkage relationship between the factor VIII gene (F8C) and the DXS52 locus was examined in 8 families. Two recombinations were identified in 35 informative meioses (Zmax = 5.67; theta = 0.05), one in a family with hemophilia A, the other in a family with the fra(X) syndrome. Based on the latter recombination, the most probable order of loci was determined to be centromere-fra(X)-DXS15-DXS52-F8C telomere. When these data are added to those reported previously the most probable genetic distance between F8C and DXS52 is 3 cM (Z = 14.62). Identification of these and other recombinations suggests that the use of DXS52 as a genetic marker for carrier detection and prenatal diagnosis of hemophilia A has an error rate between 3-5%. PMID- 3105318 TI - State government financial effort in mental retardation. AB - A comparative analysis of the level of financial effort exhibited in the states for financing mental retardation services was presented. States were ranked on a criterion (aggregate personal income) that compensated for differences in each state's financial capacity. During the FYs 1977-1984 period, on a nationwide basis, state governments spent increasingly more of their own funds for community services and increasingly less for institutional operations; however, combined institutional and community services spending was relatively stable. A hierarchical multiple regression analysis on three economic variables was performed: state size, wealth, and degree of federal assistance. All were very poor predictors of community services fiscal effort, implying the presence of more complex determinants of mental retardation spending. Degree of federal assistance was an important, inversely related, predictor of institutional fiscal effort. PMID- 3105319 TI - Influence of mannitol and dopamine on renal function during elective infrarenal aortic clamping in man. AB - The impact of elective infrarenal aortic clamping on parameters of renal function was evaluated in 27 extracellular fluid volume expanded patients. Significant transient decreases (p less than 0.05) in glomerular filtration rate were observed in all three groups either in the early or late post-clamp release period, despite maintenance of hemodynamic stability. This study documents transient decreases in glomerular filtration rate which occurred following release of the infrarenal aortic cross-clamp. No clinically important benefit from the use of mannitol and dopamine over extracellular fluid volume expansion with saline alone was demonstrated in the prevention of the changes in renal function associated with aortic cross-clamping. PMID- 3105320 TI - Keeping enteral nutrition on track. PMID- 3105321 TI - The role of glutaraldehyde-induced cross-links in calcification of bovine pericardium used in cardiac valve bioprostheses. AB - Calcification is the principal cause of failure of tissue-derived cardiac valve replacements pretreated with glutaraldehyde (GLUT). The objective of this study was to determine the role of GLUT-induced cross-links in bovine pericardial tissue calcification. Various levels of 3H-GLUT incorporation were obtained by varying incubation pH, and protein modification was determined by amino acid analysis and resistance to collagenase digestion. Calcification of cross-linked tissue was studied using subdermal implants in rats. Low GLUT uptake (less than 150 nm/mg) resulted in minimal calcification (Ca2+, 12.8 micrograms/mg) and stability (4% residual weight following digestion) due to a limited crosslinking (lysine + hydroxylysine = 26.1 residues/1000 amino acids [AA]). In contrast, higher GLUT uptake induced more cross-links (Lys + Hyl = 8.2 residues/1000 AA) and consequent higher stability (95% residual wt); such tissues calcified severely (Ca2+, 93.5 micrograms/mg). Incorporation of GLUT two to three times beyond a critical level did not further enhance calcification. It is concluded that the amount of GLUT incorporated controls the extent of cross-links, which in turn directly determines tissue stability and calcification. PMID- 3105322 TI - Distribution of lymphocytes with interleukin-2 receptors (TAC antigens) in reactive lymphoproliferative processes, Hodgkin's disease, and non-Hodgkin's lymphomas. An immunohistologic study of 300 cases. AB - The authors investigated the distribution of interleukin-2 receptors (TAC antigen) in the lymph nodes of 300 patients with lymphoproliferative disorders. They used fresh-frozen sections to evaluate a possible correlation between the immunophenotype of specific lymphoid disorders and the presence or absence of TAC expression and to determine whether the TAC positivity of lymphoid cells contributes to the characterization of lymphoproliferative processes. All of the cases had previously been studied with a large screening panel of monoclonal antibodies and polyclonal antisera. Among 85 patients with a variety of benign reactive processes, the lymph nodes from 47 contained TAC-bearing lymphocytes in various patterns of distribution. Of 41 patients with Hodgkin's disease, 37 had TAC-bearing lymphocytes. Of 26 B-cell, well-differentiated lymphocytic lymphomas (WDL), 14 were diffusely TAC-positive and one had TAC-bearing cells in random distribution. Six cases of intermediate lymphocytic lymphoma were also studied, and three showed randomly distributed TAC-bearing lymphocytes. Of 19 patients with follicular or follicular and diffuse, poorly differentiated lymphocytic (PDL) lymphoma, 14 were TAC-positive. All 3 diffuse PDL lymphomas studied were TAC-negative. Among 23 cases of B-cell and 5 cases of T-cell mixed cell lymphoma, 15 and three, respectively, had TAC-positive lymphocytes. Of 39 large cell lymphomas (B-cell, 33; T-cell, 6), 14 were TAC-positive. All 13 cases of hairy cell leukemia were diffusely positive. Of 23 T-lymphoblastic lymphomas, only 1 showed positive TAC reactivity, which was focal. Of 5 cases of cutaneous T-cell lymphoma, 2 had TAC-bearing lymphocytes. Our study indicates that the TAC antigen is not lineage-specific, and that it may be expressed by lymphoid cells regardless of their phenotype. PMID- 3105323 TI - Expression of ras oncogene p21 antigen in normal and proliferative thyroid tissues. AB - The ras oncogene p21 antigen (p21) has been identified in several epithelial malignancies, including breast, colon, bladder, and prostate. The pattern and intensity of immunoreactivity between normal and neoplastic tissues has been distinctly different. The authors examined thyroid lesions from 73 different cases by immunohistochemistry for the expression of p21 with a monoclonal antibody (RAP-5). Normal thyroid tissues (4) showed the least immunoreactivity, while papillary carcinomas (8), Hurthle cell carcinomas (10), and follicular carcinomas as (3) showed slightly more intense staining than Hurthle cell adenomas (12) or follicular adenomas (9). Anaplastic carcinomas (4) showed much less intense staining than most other carcinomas, while medullary thyroid carcinomas (5) showed only slight immunoreactivity. Inflammatory thyroid lesions associated with goiters, including Hashimoto's thyroiditis (6) and Graves' disease (8), showed moderate to intense expression of p21 as did multinodular goiters (4). Semiquantitative analysis of staining intensity by serial dilution of the primary antibody showed significant differences in staining between normal thyroid and some carcinomas (P less than 0.05), but not between carcinomas and adenomas. These results show that while antibody RAP-5 detects an antigen that is only weakly expressed in normal thyroids, this antigen is more strongly expressed in benign and malignant thyroid tumors, as well as in inflammatory and nonneoplastic proliferative thyroid lesions. It is thus not helpful in identifying differences between neoplastic and non-neoplastic thyroid lesions. PMID- 3105325 TI - Rejection of combined heart-lung transplants in rats. Function and pathology. AB - Clinical experience with combined heart-lung transplantation has made it clear that several aspects of the rejection of combined organ transplants need further investigation. In this study, the rejection process of combined heart-lung allografts was examined for determining whether it affects the lung and heart synchronously and whether it differs from rejection when these organs are transplanted alone. The lungs of the combined allografts were functionally rejected prior to the heart (6 and 11 days, respectively). Accordingly, the pathologic changes were most severe in the lungs. The rejection pathology of these combinedly transplanted organs was similar to that described for lungs and hearts transplanted separately, except that the airways were found to be more extensively involved than had been appreciated in previous studies. It is concluded that after combined transplantation the lung is more prone to rejection than the heart. On the basis of the present observations, the definition of sequential rejection phases in the lung was slightly altered. PMID- 3105326 TI - Early detection of small bilateral acoustic tumors. AB - Bilateral acoustic tumors are one of the most difficult problems in acoustic tumor surgery. Total tumor removal with preservation of hearing has seldom been achieved in the past. Recently, hearing has been successfully preserved if the tumors are small when removed. We present the case of a child with a family history of von Recklinghausen's disease associated with bilateral acoustic tumors. A high index of suspicion of bilateral tumors and a thorough work-up resulted in the early diagnosis of small tumors. The tumors were removed with preservation of normal hearing. PMID- 3105324 TI - Human chorionic gonadotropin in the rectosigmoid colon. Immunohistochemical study on unbalanced distribution of subunits. AB - For investigation of cellular localization of subunits of human chorionic gonadotropin (hCG) in normal and neoplastic rectosigmoid colon, immunohistochemical studies were performed on nonneoplastic colons (10 fetuses, 3 infants, and 23 adults, including 4 cases of ulcerative colitis) and 7 carcinoid tumors, 19 adenomas, and 50 carcinomas of the rectosigmoid colon. The alpha-hCG immunoreactive cells were present in endocrinelike cells of non-neoplastic glands (6 fetuses older than 14th gestational week, 3 infants and 19 of 23 adults). Many of the positive cells were argyrophilic, and all were nonimmunoreactive for beta subunits of glycoprotein hormones. alpha-hCG immunoreactivity was also present in many argyrophilic cells of all carcinoid tumors and in some of the endocrine cell micronests. The immunoreactive cells for isolated beta-hCG were found in 14 infiltrating carcinomas. The distribution of hCG subunits was unbalanced, and both subunits may be expressed through an independent mechanism, commonly in normal and neoplastic rectosigmoid colon. PMID- 3105327 TI - Synthesis and characterization of 19F NMR chelators for measurement of cytosolic free Ca. AB - Fluorine 19 nuclear magnetic resonance (NMR) studies of intracellular fluorinated calcium chelators provide a useful strategy for the determination of cytosolic free calcium levels in cells and perfused organs. However, the fluorinated chelator with the highest affinity for calcium ions which has been described to date. 1,2-bis-(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBAPTA), exhibits a dissociation constant (Kd) value 5- to 10-fold greater than the intracellular calcium concentration levels in most cell types, thus limiting the ability of fluorine NMR to report these concentrations reliably. We have consequently designed and synthesized several fluorinated calcium chelators with higher affinity for calcium. The best of these, 2-(2-amino-4-methyl-5 fluorophenoxy)-methyl-8 aminoquinidine-N,N,N',N'-tetraacetic acid (quinMF), has a Kd value approximately 10 times lower than that of 5FBAPTA. Several of the newly synthesized indicators have different chemical shifts for the calcium complexed and uncomplexed chelators to allow the simultaneous use of two indicators. In addition to providing information about the level of cytosolic free calcium, chelators containing a quinoline ring exhibit considerable sensitivity to magnesium levels and hence have potential application for the determination of cytosolic-magnesium concentrations. Application of these chelators is illustrated by determination of the cytosolic-free calcium level in erythrocytes. Use of quinMF, the chelator with the lowest Kd value, gives a calcium value of 25-30 nM. PMID- 3105328 TI - Adrenocortical hormone secretory response to chronic NH4Cl-induced metabolic acidosis. AB - We examined the effect of chronic metabolic acidosis on adrenocortical hormone production by administering NH4Cl for 5 days to four normal subjects. Plasma aldosterone concentration, aldosterone secretion, and urinary excretion of aldosterone-18-glucuronide increased significantly, whereas there were no significant changes in the plasma concentrations of cortisol, corticosterone, or deoxycorticosterone, or in the urinary excretion of 17-hydroxycorticoids. By day 2, plasma renin activity (PRA) and concentration (PRC) were not significantly different from control, and the slope of the regression line relating plasma aldosterone concentration to PRA was significantly greater than the slope in the control period, i.e., the sensitivity of aldosterone secretion to renin stimulation was increased. By day 5, however, PRA and PRC were increased above control. Plasma potassium concentration did not change significantly. Thus chronic NH4Cl-induced acidosis induces a sustained stimulation of aldosterone secretion in the absence of a change in adrenocorticotropin-dependent adrenocortical hormone secretion. Factors other than an increase in renin secretion and plasma potassium concentration may be involved in at least the early phase of aldosterone stimulation, suggesting that plasma hydrogen ion concentration might be a separate regulator of aldosterone secretion. PMID- 3105329 TI - Role of luteinizing hormone in luteotropic complex of pregnant hamster. AB - Hamsters were hypophysectomized on day 4 of pregnancy (day 1 = sperm in vaginal smear) and injected subcutaneously on days 4-7 with various combinations of 200 micrograms prolactin (Prl), 10 micrograms follicle-stimulating hormone (FSH), and 20 micrograms luteinizing hormone (LH) in polyvinylpyrrolidone (PVP) to decrease its rate of absorption or in saline. End points for luteal function on day 8 were maintenance of pregnancy, serum progesterone (P4), luteal weight, and luteal binding for human chorionic gonadotropin, FSH, and Prl. After hypophysectomy, a drastic decline occurred in all parameters including an 89% decrease in luteal weight. Injection of Prl did not maintain pregnancy nor serum P4 but partially maintained luteal weight and human chorionic gonadotropin binding sites per corpus luteum. The minimal luteotropic complex of Prl and FSH was effective in maintaining pregnancy and significantly increased serum P4 and Prl and FSH receptors but not to control levels; Prl and LH (PVP) was also effective to the same extent. Antral follicles were lacking after either treatment. The effects of FSH cannot be attributed to LH contamination. All variables were restored to control levels by Prl plus FSH plus LH (PVP) and antral follicles were present; Prl plus FSH plus LH (saline), however, induced luteolysis and reduced most values to the levels found in untreated, hypophysectomized animals. Thus, the luteotropic activity of LH was only demonstrable when it was injected in a long acting form; when delivered as a bolus, LH (saline) was luteolytic. PMID- 3105330 TI - Role of ornithine decarboxylase in functional development of rat gastric mucosa. AB - The effects of inhibiting polyamine synthesis on the functional development of the gastric mucosa were studied in rats from 5 to 40 days old. They were treated from day 14 after birth with alpha-difluoromethylornithine (DFMO) at a concentration of 2% in the drinking water of mothers and pups. The rats were weaned on day 18. Basal acid and pepsin secretion, oxyntic gland mucosal pepsinogen content, and antral gastrin content followed similar developmental patterns in control animals. Levels of these parameters remained measurable but low until around the time of weaning, when dramatic log linear rises were observed. DFMO failed to delay the onset of the rises in any of these maturational indices. Ornithine decarboxylase (ODC) activity in the oxyntic gland mucosa was low but discernible in rats of every age studied. DFMO significantly reduced ODC activity at every age except 40 days, where there was no difference from control values. Our results suggest that ODC activity in the rat gastric mucosa does not change appreciably during neonatal development and that inhibiting putrescine synthesis from its precursor ornithine by DFMO treatment does not prevent or delay gastric mucosal maturation. PMID- 3105331 TI - Endocytosis by cultured mesangial cells and associated changes in prostaglandin E2 synthesis. AB - The mechanism of macromolecule uptake by cultured mesangial cells was studied by use of transmission electron microscopy. In parallel, we investigated the effect of macromolecular uptake on prostaglandin E2 (PGE2) formation. Cultured rat mesangial cells were studied in their third passage. As model molecules, we used colloidal gold particles (10 nm diameter) coated either with polyethylene glycol (PEG) or fresh serum (SCG). Mesangial cells were incubated from 1 to 60 min and up to 12 h with either PEG or SCG particles. Endocytosis of SCG significantly exceeded that of PEG particles. The mechanism involved binding to coated pits, followed by formation of coated vesicles (endosomes), and eventually delivery of particles to lysosomes. Pretreatment with cytochalasin B virtually prevented endocytosis of SCG particles, indicating active participation of the cytoskeleton. Determination of PGE2 production in parallel showed that SCG significantly stimulated PGE2 synthesis within minutes, whereas PEG-coated gold had no effect. When gold particles were coated with decomplemented serum instead of fresh serum, the stimulation of PGE2 was partially, but not completely, prevented, indicating that complement may be one, but not the only ligand responsible for enhanced PGE2 production. Stimulation of PGE2 synthesis by SCG was not dependent on actual endocytosis, as it was not altered by cytochalasin B pretreatment. Thus, surface ligand-receptor interaction may be sufficient to trigger PGE2 synthesis. The interaction between mesangial endocytosis and PGE2 production may be important for glomerular pathophysiology. PMID- 3105332 TI - Biphasic effect of oxygen radicals on prostaglandin production by rat mesangial cells. AB - Cultured rat mesangial cells were exposed to a reactive oxygen species (ROS) generating system (xanthine plus xanthine oxidase) to explore the effect of ROS on their metabolism of arachidonic acid (AA). Cell viability, as assessed by 51Cr release, was not affected by the concentrations of xanthine plus xanthine oxidase used. Prostaglandin E2 (PGE2) production following exposure to increasing quantities of xanthine plus xanthine oxidase was significantly decreased to 38.1 +/- 9.7 or 30.8 +/- 6.9% of control levels (P less than 0.05) when cells were stimulated with the calcium ionophore A23187 (1 microgram/ml) or AA (10(-6) M), respectively. Maximum suppression of production was seen within 10 min of ROS exposure. Thromboxane B2 production was similarly decreased to 83.1 +/- 7.6 (0.05 less than P less than 0.10) or 54.9 +/- 2.5% (P less than 0.05). This effect was reversed by addition of catalase to the ROS generating system but not by superoxide dismutase or mannitol, which suggested that H2O2 was the responsible metabolite. High levels of H2O2 (5 x 10(-4) M) suppressed PGE2 production to 44.0 +/- 4.1 or 17.4 +/- 6.2% of A23187- or AA-stimulated production (P less than 0.05). Lower levels of H2O2 resulted in significant stimulation of base-line PGE2 production. Analysis of release of [3H]AA-labeled metabolites from A23187 stimulated cells showed no effect of H2O2 on phospholipase activity. Thus ROS can stimulate or inhibit AA metabolism in the glomerular mesangium, which may have important effects on glomerular hemodynamics during glomerular injury. PMID- 3105333 TI - Effects of coronary occlusion on arterial baroreflex control of heart rate and vascular resistance. AB - This study was planned to assess whether circumflex coronary occlusion (CO) impairs the arterial baroreflex control of heart rate (HR) and hindlimb vascular resistance (HVR), and to determine the mechanisms involved in the mediation of these phenomena. Increasing doses of phenylephrine and nitroglycerin were given intravenously to anesthetized dogs with a constant flow-perfused hindlimb before and during 30-s CO. The reflex responses were assessed by the changes in HR and hindlimb perfusion pressure evoked by changes in arterial pressure following phenylephrine and nitroglycerin administration. During CO, there was an attenuation of the reflex control of HR and HVR as compared with control conditions. The application of lidocaine on the left ventricular epicardial surface was able to prevent the effect of CO on both the baroreflex responses. The intravenous administration of atropine prevented only the impairment in arterial baroreflex control of HR induced by CO. After the injection of phentolamine into the perfused hindlimb, the baroreflex had no effect on HVR either before or during CO. Finally, intravenous administration of propranolol failed to modify the effect of CO on both the baroreflex responses. These data indicate that CO attenuates the arterial baroreflex control of both HR and HVR through the stimulation of left ventricular receptors. The effect on HR is mediated by the parasympathetic system, whereas the effect on HVR is due to sympathetic efferents. PMID- 3105334 TI - TRH-induced TSH response in healthy volunteers: relationship to psychiatric history. AB - The authors measured thyroid-stimulating hormone (TSH) response to thyrotropin releasing hormone in 32 healthy volunteers who had never sought or received psychiatric treatment. Nine (28%) had a family or personal history of depression or alcoholism. Five of these nine subjects and one of 22 subjects without such a history showed TSH blunting (TSH data were not available for one subject). This difference was statistically highly significant. Although there were sex differences in TSH response, TSH blunting occurred most frequently in men with a family or personal history of depression or alcoholism. The fault may have utility as a marker of past episodes or as a true marker of trait. PMID- 3105335 TI - DST and TRH stimulation test in mood disorder subtypes. AB - Both the dexamethasone suppression test (DST) and the thyrotropin-releasing hormone (TRH) stimulation test have been reported to be useful in subtyping some depression diagnoses. Whether the DST discriminates delusional from nondelusional depression remains controversial, but this possibility has not been studied for the TRH test. The authors evaluated DST and TRH test results in 29 depressed hospitalized patients; both tests significantly discriminated patients with nonendogenous depression from those with endogenous depression. Furthermore, postdexamethasone cortisol levels but not the change in thyroid-stimulating hormone discriminated the patients with endogenous delusional depression from those with endogenous nondelusional depression. PMID- 3105337 TI - How problematic are nosocomial infections in the DRG reimbursement system? PMID- 3105336 TI - TSH and prolactin responses to TRH in patients with premenstrual syndrome. AB - The thyroid-stimulating hormone (TSH) and prolactin responses to thyrotropin releasing hormone (TRH), administered during the follicular and luteal phases of the menstrual cycle, were examined in 14 women with prospectively confirmed premenstrual syndrome and in nine control subjects. There were no differences in basal or maximum increase in TSH or prolactin values between menstrual cycle phases in patients or in control subjects or between patients and control subjects in either phase. However, there was significantly greater variability in TSH response to TRH among symptomatic patients (seven of 10 patients: three with blunted and four with augmented response) than among control subjects (none of nine patients). PMID- 3105338 TI - Reliability of reporting nosocomial infections in the discharge abstract and implications for receipt of revenues under prospective reimbursement. AB - Proper reporting of discharge diagnoses, including complications of medical care, is essential for maximum recovery of revenues under the prospective reimbursement system. To evaluate the effectiveness of abstracting techniques in identifying nosocomial infections at discharge, discharge abstracts of patients with nosocomial infections were reviewed during September through November of 1984. Patients with nosocomial infections were identified using modified Centers for Disease Control (CDC) definitions and trained surveillance technicians. Records which did not include the diagnosis of nosocomial infections in the discharge abstract were identified, and potential lost revenues were estimated. We identified 631 infections in 498 patients. On average, only 57 per cent of the infections were properly recorded and coded in the discharge abstract. Of the additional monies which might be anticipated by the health care institution to assist in the cost of care of adverse events, approximately one-third would have been lost due to errors in coding in the discharge abstract. Although these lost revenues are substantial, they constitute but a small proportion of the potential costs to the institution when patients acquire nosocomial infections. PMID- 3105339 TI - Newborn duodenal atresia: an improving outlook. AB - From 1973 through 1983, 20 newborns with congenital duodenal atresia were treated. These patients are compared with our previous series and with other published series. There were no fatalities among the 19 patients who underwent operation, an improvement from the 72 percent survival rate in our previous series. Fifty-five percent of the patients had associated congenital anomalies, which frequently complicated their management. The use of a transanastomotic jejunal feeding tube resulted in delayed oral feeding and prolonged hospitalization, and cannot be recommended. PMID- 3105340 TI - Infectious complications with the use of cyclosporine versus azathioprine after cadaveric kidney transplantation. AB - Infectious complications within 1 year of cadaveric kidney transplantation were compared in 45 patients treated with azathioprine, prednisone, and antilymphocyte globulin and 38 patients treated with cyclosporine and prednisone. Although there was no difference in the 1 year patient or graft survival rate, cyclosporine treated patients had significantly fewer wound infections, infection-related transplant nephrectomies, and infection-related graft failures than azathioprine treated patients. The cyclosporine-treated diabetic recipients had more nonviral pneumonias and opportunistic infections but fewer cases of infection-related transplant nephrectomy than did the azathioprine-treated diabetic patients. Our data suggest cyclosporine is associated with reduced infectious morbidity after cadaveric kidney transplantation in nondiabetic patients. PMID- 3105341 TI - Vaccines and antibody immunotherapy in surgical patients. AB - Immunoprophylaxis of infectious complications in surgical patients is currently practiced and is efficacious for disease caused by Clostridium tetani, rabies virus, Streptococcus pneumoniae, and hepatitis B virus. Evidence exists that immunoprophylaxis and treatment of herpes viruses as well as gram-negative pathogens is possible, although extensive clinical testing will be required to establish immunotherapy as a effective clinical treatment modality for the control of disease caused by these agents. Advances in our understanding of the host immune response and the ways in which it may be stimulated or supplemented should provide the means to further reduce the morbidity and mortality caused by a variety of pathogenic microbial agents. PMID- 3105342 TI - High-grade malignant cutaneous plasmacytoma metastatic to the central nervous system. A case report with electron microscopy, immunohistological, and neuropathological studies. AB - A case of high-grade malignant extramedullary plasmacytoma (EMP), unusual in its initial cutaneous localization and major involvement in the central nervous system rapidly resulting in death, is reported. Light- and electron-microscopic studies of a skin nodule revealed a high proportion of immature and mature plasmacytes. Immunohistological study revealed that both cells synthesized different amounts of a monotypic cytoplasmic kappa light chain. Neuropathological study revealed extensive infiltration of the leptomeninges and perivascular spaces as far as the deep parenchyma. In several places, effraction of vessels resulted in parenchymatous, tumor-like, plasmacytic infiltration. The findings of this case were compared with those of the few previously reported cases of EMP with initial cutaneous or intracranial localization, and with those of immunoblastic sarcoma occurring in some cases of myeloma. PMID- 3105343 TI - Central nervous system prostaglandins and ethanol. AB - There is growing interest in the effect of ethanol on cellular membranes, generally, and neuronal membrane systems, in particular. Perturbations of membranes have led to numerous enzymatically mediated processes, one of which is prostaglandin production. This paper reviews the nature and role of prostaglandins in the central nervous system, and what is known about the effect of ethanol on prostaglandin production in brain. Areas of central nervous system physiological function in which prostaglandins may mediate the actions of ethanol are discussed. Methodological considerations and future directions for research in the area of ethanol and prostaglandins are highlighted. PMID- 3105344 TI - Acute alcohol intoxication in women: relationship to dose and menstrual cycle phase. AB - This study investigated relationships between metabolic responses to acute alcohol intoxication and phases of the female menstrual cycle among women demonstrated to have ovulated during two consecutive cycles. Subjects were administered moderate (0.66 ml/kg) and high (1.0 ml/kg) alcohol doses during the early follicular, ovulatory, and midluteal phases of the menstrual cycles. Radioimmunoassays (RIAs) of serum estradiol, progesterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were performed from blood collected before each alcohol administration. Results showed decreased elimination times, reduced areas under the BAC-time curve (AUCs), and faster disappearance rates associated with the midluteal menstrual phase compared to the early follicular and ovulatory phases which were consistent for both moderate and high alcohol doses. Decreased elimination times, smaller AUCs, and faster disappearance rates were associated with increased levels of progesterone, elevated progesterone to estradiol ratios, and decreased FSH levels. No differences were found in absorption time or peak BAC across phases of the menstrual cycle. PMID- 3105345 TI - Costs, severity of illness and outcome in intensive care. AB - Severity of illness (Therapeutic Index Severity Score, Classes 1-4) and direct clinical costs (labour costs, diagnostic costs, drugs, disposables, etc.) were determined for 100 consecutive patients admitted to Royal Newcastle Hospital Intensive Care Unit over six weeks. Outcome was assessed using mortality, quality of life, functional status, productivity and mental status one month after separation from the Unit. The mean total admission cost was $1,357 (Class 4 mean = $3,706) but for over 70% of patients costs were less than $1,000. The main component of cost was labour (about 60% for all classes). TISS proved a strong predictor (P less than 0.001) of total admission costs. Survival to one month was 89% and optimal association between cost and survival was found with those with low costs more likely to survive (P less than 0.001). On the other hand, no association was found between total admission cost and resulting quality of life. However, there was an association between pre-admission and follow-up quality of life (P less than 0.0005). PMID- 3105346 TI - Antimicrobial activity of bupivacaine and pethidine. AB - The antimicrobial activity of bupivacaine and pethidine in concentrations commonly used in epidural practice was studied by an agar dilution method against ten common micro-organisms. Both drugs showed increasing microbe inhibition with increasing drug concentrations. Bupivacaine at common epidural concentrations inhibited eight of the ten organisms and pethidine inhibited six. These findings confirm previous reports of microbe inhibition by bupivacaine, and in addition demonstrate a similar but slightly lesser activity by pethidine. Although antimicrobial activity of epidural drugs can be regarded as a desirable property, clinical implications of such findings remain unclear. PMID- 3105348 TI - Radioiodination of proteins by reductive alkylation. AB - The use of the aliphatic aldehyde, para-hydroxyphenylacetaldehyde as the reactive moiety in the radioiodination of proteins by reductive alkylation is described. The para-hydroxyphenyl group is radiolabeled with 125I, reacted through its aliphatic aldehyde group with primary amino groups on proteins to form a reversible Schiff base linkage which can then be stabilized with the mild reducing agent NaCNBH3. The introduction of the methylene group between the benzene ring and the aldehyde group increases its reactivity with protein amino groups permitting efficient labeling at low aldehyde concentrations. Using this method, radioiodinated proteins with high specific activity can be produced. The reductive alkylation procedure is advantageous in that the labeling conditions are mild, the reaction is specific for lysyl residues, and the modification of the epsilon-ammonium group of lysine results in ionizable secondary amino groups avoiding major changes in protein charge. PMID- 3105347 TI - Computational analysis of density gradient distribution profiles. AB - A method is presented for the construction of distribution profiles following subcellular fractionation by density gradient centrifugation. The method allows reconstruction of the frequency-density distributions over user-defined density limits, enabling averaging of results from multiple experiments. An alternative format for data presentation, that of relative concentration versus density, is also introduced. This overcomes some practical problems associated with frequency density distribution profiles. The technique utilizes a direct noniterative approach to curve fitting and can easily be implemented on microcomputers. PMID- 3105350 TI - High-performance liquid chromatographic quantitation of desmosine plus isodesmosine in elastin and whole tissue hydrolysates. AB - Quantitation of desmosine and isodesmosine, the major crosslinks in elastin, has been of interest because of their uniqueness and use as markers of that protein. Accurate measurement of these crosslinks may allow determination of elastin degradation in vivo and elastin content in tissues, obviating lengthy extraction procedures. We have developed a method of quantitating desmosine plus isodesmosine in hydrolysates of tissue and insoluble elastin using high performance liquid chromatographic separation and absorbance detection that is rapid (21-35 min) and sensitive (accurate linearity from 100 pmol to 5 nmol). This method has been used to quantitate desmosines in elastin from bovine nuchal ligament and lung and in whole aorta from hamster. The ability to completely separate [3H]lysine from desmosine plus isodesmosine allows the method to be used to study incorporation of lysine into crosslinks in elastin. PMID- 3105349 TI - Analysis of the stereochemistry of lipoxygenase-derived hydroxypolyenoic fatty acids by means of chiral phase high-pressure liquid chromatography. AB - A chiral phase HPLC method was developed for the simultaneous determination of the positional and optical isomers of the lipoxygenase-derived hydroxypolyenoic fatty acids. With a Bakerbond chiral phase HPLC column (dinitrobenzoyl phenylglycine as chiral phase) the positional and optical isomers of the reduced dioxygenation products (by triphenylphosphine or borohydride) of linoleic acid and arachidonic acid were separated after methylation of the carboxylic groups. No cumbersome chemical derivatization such as conversion to a diastereomer was necessary. As compared with the methods used up till now chiral phase HPLC proved to be simpler and more sensitive. About 10 pmol of hydroxy fatty acids suffice for an analysis. The chiral phase HPLC can be used for the preparative separation of the optical antipodes of the lipoxygenase products. An optical purity of more than 90% can be reached in one preparative run. The method was applied to the determination of the stereochemistry of the dioxygenation products of polyenoic fatty acids formed by the lipoxygenases from soybeans, reticulocytes, pea seeds (isoenzyme I and II), tomato fruits, by the quasilipoxygenase activity of hemoglobin, and by the methylene blue-mediated photooxidation of arachidonic acid. PMID- 3105351 TI - Dating techniques in archaeology and paleoanthropology. PMID- 3105352 TI - Oxygen isotope ratio measurements on carbon dioxide generated by reaction of microliter quantities of biological fluids with guanidine hydrochloride. PMID- 3105354 TI - Analytical reference materials. Part VII. Development and certification of a sediment reference material for total polychlorinated biphenyls. PMID- 3105353 TI - Supercritical fluid-based sample introduction for inductively coupled plasma atomic spectrometry. PMID- 3105355 TI - Determination of polychlorinated biphenyls in waste oil by gas-liquid chromatography. PMID- 3105356 TI - Comparative study on carbonic anhydrase activity in the retina of different birds during development. AB - In the retina of vertebrates, carbonic anhydrase (CA) is present in the cells of the pigmented epithelial layer and in Muller cells. Its activity has been demonstrated to increase during development, corresponding to the maturity of the tissue. We have studied CA activity, either during embryonic development or after hatching, in the retina of 3 species of birds, having precocial or atricial broods. The research has been carried out, by histochemical and biochemical methods, in pigeon as an example of atricial brood, and in fowl and quail, that represent examples of precocial broods. Our results confirmed that CA activity may be taken as a marker of retina maturity, or, more precisely, of Muller cells maturity, for any species of vertebrates, depending solely on maturity of the offspring at birth time. PMID- 3105358 TI - Regression lines using multiple measurements from multiple patients. PMID- 3105357 TI - Effects of a specific benzodiazepine antagonist (RO 15-1788) on cerebral blood flow. AB - RO 15-1788, a specific benzodiazepine antagonist, although it effectively antagonizes the clinical effects of benzodiazepines (i.e., sedation and amnesia), can also induce subjective agonist effects such as sedation or inverse agonist effects such as anxiety. The purpose of this study was to investigate in seven healthy volunteers the effect of RO 15-1788 on cerebral blood flow when intravenously injected alone or with midazolam and to compare its effects with midazolam administered alone. Cerebral blood flow was measured with the 133xenon inhalation technique and the drugs were administered simultaneously in a double blind, randomized fashion during the four following sessions: placebo-placebo; midazolam-placebo; RO 15-1788-placebo; midazolam-RO 15-1788. No difference in cerebral blood flow was noted between the placebo-placebo, the RO 15-1788 placebo, and the RO 15-1788-midazolam sessions--although midazolam injected alone decreased cerebral blood flow by 30%. The sedation, amnesia, and the electroencephalograph (EEG) and muscle tone changes observed with midazolam placebo were not present during the RO 15-1788-placebo and RO 15-1788-midazolam sessions. This study demonstrates the absence of effects of RO 15-1788 on cerebral blood flow when injected alone and the efficacy of this new drug in antagonizing the depressant effects of midazolam on cerebral hemodynamics. PMID- 3105359 TI - Another technique for extending the life of oximetry monitoring probes. PMID- 3105361 TI - Video induction: CO2 wars. PMID- 3105360 TI - The actions of halothane, ibuprofen and BW755C on hypoxic pulmonary vasoconstriction. AB - The effect of halothane on the pressor responses to hypoxia (3% O2, 5% CO2, balance N2) and to Angiotensin II (Ang II) (0.2 microgram) has been compared in an in vitro perfused and ventilated rat lung preparation in the presence and absence of agents known to block the lipoxygenase (BW755C) and/or the cyclooxygenase (ibuprofen) pathways for arachidonic acid metabolism. Preliminary studies established the stability of the preparation (experiment 1) during two hours of observation and allowed estimation of (experiment 2) the concentration of BW755C that inhibited the HPV response by 50% (ED50 = 125 microM). In experiment 3, the rat lungs were subdivided into four groups: A, B, C, and D. Group A received the drug solvent, and B received 17 microM ibuprofen. Groups C and D received ibuprofen and, in addition, an ED50 dose of BW755C. The lungs were then tested for their response to hypoxia. In addition, groups C and D were tested for their response to 0.2 microgram Ang II. 0.5 MAC halothane was introduced into the ventilatory circuit of A, B, and D. Group C received no halothane. Responses to hypoxia and Ang II (groups C and D) were measured. Halothane was terminated and a further hypoxic response was tested in groups A and B. The results show, in group A, that the addition of halothane reduced the response to hypoxia from (mean +/- SE cm H2O) 13.4 +/- 1.56 to 6.5 +/- 1.28, a 50% reduction. The addition of ibuprofen in group B caused a 33% increase in the response, and the addition of halothane now caused only a 30% decrease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105362 TI - Diazepam and the hypercarbic response to carbon dioxide. PMID- 3105363 TI - [Medico-economic analysis of antithrombotic prophylaxis versus no prophylaxis in traumatology. Study of 920 cases]. PMID- 3105364 TI - Effectiveness of an infection control programmed unit of instruction in nursing education. AB - To determine whether programmed instruction is an acceptable, cost-effective alternative to classroom lectures for teaching the basic principles of infection control to nursing students, a 46-frame programmed unit of instruction (PUI), with a pretest and posttest, was developed, piloted, and tested for reliability and validity. The instruments were developed on the basis of current knowledge of the epidemiology of infectious diseases and the 1983 revised Centers for Disease Control guideline for category-specific isolation precautions. A study was undertaken to test the hypothesis: Student nurses who take a PUI in the basic principles of infection control will score higher on posttests than those who do not take the PUI. A sample of 40 subjects was selected from the senior class in a baccalaureate nursing program at a public university. The subjects were randomly assigned to four groups of 10. A Solomon four-group design was used for data analysis, and a two-way analysis of variance was performed on the posttest means. Results indicated that the treatment (PUI) effect was significant (p less than 0.001). Therefore, it was concluded that the PUI in the basic principles of infection control is an effective instrument for nursing education. PMID- 3105365 TI - Role of rapid tests for streptococcal pharyngitis in hospital infection control. AB - Rapid streptococcal antigen detection tests are now an alternative to throat cultures for diagnosing group A streptococcal pharyngitis. Used alone, they are not suitable for hospital infection control applications because of the risk that individuals with streptococcal pharyngitis and a falsely negative test will spread the infection within the institution. However, a rapid test may be an economical method for screening employees with pharyngitis, provided that a throat culture is performed for everyone with a negative test. Compared with the use of throat cultures alone, this strategy reduces the number of missed diagnoses and the number of work days lost. Cost-benefit analysis shows that over a wide range of streptococcal prevalence and carrier rate the total cost is also less with the use of rapid tests first. If the prevalence of streptococcal pharyngitis is very low, the use of cultures alone is more cost-effective. PMID- 3105367 TI - Selective venous hypercarbia during human CPR: implications regarding blood flow. AB - Thirty-five patients presenting to the emergency department in cardiopulmonary arrest had simultaneous measurement of central venous (cv) and arterial (a) blood gases during CPR with a pneumatic chest compressor and ventilator. The mean cv, arterial pH, and PCO2 values were markedly different (P less than .001). The mean pH gradient (pHa - pHcv) was .31 +/- .10 units and the mean PCO2 gradient (PcvCO2 - PaCO2) was 60.5 +/- 23.6 torr. This selective venous hypercarbia is probably due to a cardiac output that is inadequate to eliminate the CO2 produced from both residual aerobic metabolism and the buffering of anaerobically produced lactic acid. Central venous blood gases are probably a better reflection of actual tissue environment during prolonged cardiac arrest than are arterial blood gases. PMID- 3105366 TI - Mediators of human mast cells and human mast cell subsets. AB - Although a great deal has been learned about the mediators produced by mast cells, the ultimate biologic function(s) of mast cell remains a mystery. Histamine, LTC4, PAF, and possibly tryptase (C3a generation) all enhance vasopermeability. Mediators with anticoagulant activities such as heparin and tryptase (fibrinogenolysis) and antithrombotic activity, PGD2, would appear to facilitate dispersion in tissues of the plasma ultrafiltrate brought there by the subgroup of mediators that enhance vasopermeability. In contrast, PAF causes platelet aggregation and chymase may cause arteriolar vasoconstriction (decreasing the volume of plasma reaching venules) by generation of angiotensin II. Assessment of any differential production of mediators by different types of mast cells will be of obvious importance in sorting out the physiologic responses to mast cell activation as well as the pathophysiology of allergic reactions. PMID- 3105368 TI - Facilitated intravenous access through local application of nitroglycerin ointment. AB - Thirty-four patients with diminutive peripheral veins requiring peripheral IV access (PIVA) in the emergency department setting were randomly assigned to one of two treatment groups. One group of patients (Group A) received application of a bland ointment to the dorsum of the hand prior to attempts at cannulation, while the other group (Group B) received application of 2% nitroglycerin ointment to the dorsum of the hand prior to cannulation attempts. Cannulation was achieved in all 34 patients in the study, but required significantly fewer attempts in Group B patients (P = .04). No side effects of the drug were observed in any patient or any staff member applying the ointments. We conclude that application of 2% nitroglycerin ointment to the dorsum of the hand is a safe, effective method of inducing local venodilation that will ensure PIVA with significantly fewer attempts at cannulation. PMID- 3105369 TI - Seroreactivity of Peruvian sheep and goats to small ruminant lentivirus-ovine progressive pneumonia virus. AB - Sera from 3,369 sheep and 1,394 goats in Peru were examined by agar-gel immunodiffusion for antibodies to ovine progressive pneumonia virus (OPPV). The point prevalence rates for antibodies to OPPV in sheep were 1.7% to 40.6% (mean, 19.02%) in the 7 flocks studied, whereas for goats, the point prevalence rates for antibodies that cross-reacted with OPPV in 12 herds were 0.0% to 45.1%. For sheep, a direct association between increasing age and increasing seroreactivity to OPPV was established, and there was evidence to indicate that lambs born to primiparous ewes and raised separated from all other sheep after they were weaned may have been less likely to become infected with OPPV than those lambs born to multiparous ewes and not separated from other sheep after they were weaned. For goats, antibodies to OPPV were detected in 7 of 12 herds studied, the highest infection rate being present within a herd in the Lima department (district). PMID- 3105370 TI - BW755C modifies endotoxin-induced respiratory failure in pigs. AB - The porcine pulmonary response to endotoxemia was evaluated before and after 3 amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW755C), a dual inhibitor of the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Escherichia coli endotoxin (055-B5) was infused IV into anesthetized 10- to 14-week-old pigs at 5 micrograms/kg the first hour, followed by 2 micrograms/kg/hr for 3.5 hours. The BW755C was infused at 20 mg/kg before endotoxin was administered and at 2.2 mg/kg during endotoxemia. During phase 1 (ie, 0 to 2 hours), the endotoxin-induced pulmonary hypertension, increased pulmonary vascular resistance and alveolar-arterial oxygen gradient, and decreased cardiac index and lung dynamic compliance were blocked or modified by BW755C. During phase 2 endotoxemia (ie, 2 to 4.5 hours), BW755C modified or blocked the increases in pulmonary vascular pressures, pulmonary vascular resistance, alveolar dead space ventilation, alveolar-arterial oxygen gradient, lung water, and bronchoalveolar lavage albumin concentration. The BW755C also modified the phase 2 decreases in cardiac index, lung dynamic compliance, and aortic platelet count. With regard to the endotoxin-induced pulmonary vasoconstriction, bronchoconstriction, and impairment of gas exchange, the data do not support a role for lipoxygenase metabolites, because the modified blockade (provided by BW755C) was of no greater magnitude than that reported for indomethacin (cyclooxygenase blocker). However, the data supports a possible role for lipoxygenase metabolites with regard to altering vascular permeability, cardiac index, and aortic platelet count. PMID- 3105372 TI - As I see it ... Nurses must cope in competitive health care system. PMID- 3105371 TI - Placental transfer of specific antibodies during ovine congenital toxoplasmosis. AB - The passage of non-Toxoplasma antibodies from dam to fetus through damaged placenta was studied in sheep inoculated with Toxoplasma gondii. Six ewes were inoculated with chicken globulins and Leptospira bacterins 2 months before oral inoculation with Toxoplasma gondii oocysts. Ewes were euthanatized between 42 and 62 days after T gondii inoculation. Antibody titers against chicken globulins, Leptospira spp, Haemonchus contortus, Sarcocystis spp, and T gondii were measured in the maternal and fetal sera. All ewes became infected with T gondii and had grossly visible necrotic foci in the placentas, and T gondii antibodies were found in the fetuses and the ewes. Appreciable amounts of antibodies to Haemonchus contortus, Sarcocystis sp, Leptospira spp, and chicken globulins did not cross the placental barrier. Seemingly, serologic examination of the fetus was reliable for the diagnosis of ovine congential toxoplasmosis. PMID- 3105373 TI - Fast solubilization of human lung elastin by Pseudomonas aeruginosa elastase. AB - Pseudomonas aeruginosa may cause severe lung infections in humans. This bacteria secretes an elastase that might degrade lung elastin. We have studied the solubilization of human lung elastin by P. aeruginosa elastase in an attempt to delineate the pathogenic role of this proteinase in P. aeruginosa lung infections. We also used bovine ligamentum nuchae elastin and human leukocyte elastase for comparative purposes. With an elastin concentration of 5 mg X ml-1 and at physiologic ionic strength, P. aeruginosa elastase is about 50 times more active on human lung elastin than on bovine elastin. In contrast, human leukocyte elastase has similar specific activities on the 2 substrates. In addition, the bacterial enzyme is about 10 times more active on human elastin than the neutrophil elastase but the latter is about 5 times more active on bovine elastin than the former. In order to better quantitate these enzyme-substrate interactions, we have measured initial rates of elastolysis, derived from product versus time curves, as a function of elastin concentration. The substrate velocity curves, analyzed using an equation similar to the classic Michaelis Menten one, yielded 2 empirical kinetic parameters: [S50]-1, the apparent elastase-elastin affinity and Vm, the apparent catalytic efficiency of elastase. This analysis shows that human leukocyte elastase exhibits similar [S50]-1 and Vm values for the 2 elastins. The low activity of P. aeruginosa elastase on bovine elastin is due to the combined effects of low S50(-1) and Vm values, which could not be measured separately.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105374 TI - Human heart-lung transplantation: physiologic aspects of the denervated lung and post-transplant obliterative bronchiolitis. AB - Eighteen sequential follow-up measurements of pulmonary function were obtained over a period of 21 months after heart-lung transplantation in a patient who had undergone surgery for end-stage pulmonary lymphangioleiomyomatosis. In the early postoperative period, there was a moderate decrease in VC and TLC but gas exchange was maintained at essentially normal levels. The most conspicuous features of postoperative lung function were a very low airway resistance and an increase in FEV1/VC ratio above 95%. These alterations were associated with an unusual shape of the maximal expiratory flow-volume (MEFV) curve. Instead of showing a uniform decrease in expiratory flow as expiration proceeds to residual volume, the post-transplant MEFV curve showed a peak followed by a gently sloping plateau ending at a knee where flow suddenly fell. The knee occurred after exhalation of 80% VC. From the sixth postoperative month, the patient developed rapidly increasing air-flow obstruction, which proved to be due to obliterative bronchiolitis. As air-flow obstruction worsened, the knee on the MEFV curve progressively occurred at a higher lung volume, the flow plateau shortened, and flow after the knee became smaller at a given volume. From the ninth postoperative month, it was no longer possible to identify a plateau-knee configuration on the MEFV curve, which resembled that seen in severe obstructive airway disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105375 TI - Nosocomial infection by gentamicin-resistant Streptococcus faecalis. An epidemiologic study. AB - Enterococci with high-level resistance to gentamicin account for 55% of clinical isolates of enterococci found in patients at the Ann Arbor Veterans Administration Medical Center. We prospectively studied cultures obtained from all 100 patients hospitalized from 1 December 1985 through 23 January 1986 on the surgical and thoracic intensive care units and a general medical floor. Ten patients' cultures grew colonies of gentamicin-resistant enterococci--six after admission to the intensive care units and four after hospitalization on the medical ward. The initial sites of colonization were the rectal and perineal areas in seven patients, sternal wound in one, urine in one, and the rectal and perineal areas as well as urine after Foley catheter insertion in one. Nine patients died and three of the deaths were associated with enterococcal infection. The acquisition of resistant strains was associated with previous and more frequent exposure to antimicrobial agents, and with geographic clustering of patients. Resistant enterococci were isolated from the hands of hospital personnel and were frequently isolated from environmental surfaces. Nosocomial acquisition and interhospital spread of gentamicin-resistant enterococci was shown to have occurred when plasmid content was used as an epidemiologic marker. PMID- 3105376 TI - The enterococcus: "putting the bug in our ears". AB - High-level resistance to gentamicin among clinical isolates of enterococci has been found with increasing frequency in recent years. In this issue, Zervos and colleagues report findings from a prospective study in which they assessed the frequency of colonization and infection with such organisms at a university medical center, demonstrating probable person-to-person spread. Their findings suggest that hospitals should conduct systematic screening for enterococci with high-level resistance to gentamicin, that antimicrobial treatment habits be modified to limit the emergence of such organisms, and that rigorous infection control be practiced to minimize their spread. These observations are particularly timely because it has become clear that enterococci are extremely versatile pathogens which are both well suited for survival and capable of causing serious illness, especially in hospitalized patients treated with some of the newer broad-spectrum antibiotic agents. Enterococci with high-level resistance to gentamicin are also of growing concern because their resistance to many antibiotic agents severely limits the clinician's options for treatment. PMID- 3105377 TI - Primary bile duct cancer and von Recklinghausen disease. PMID- 3105378 TI - Anti-rhesus antibodies, immune thrombocytopenia, and human immunodeficiency virus treatment. PMID- 3105379 TI - Soluble interleukin-2 receptors in B-cell leukemia and the acquired immunodeficiency syndrome. PMID- 3105380 TI - Endocarditis after lithotripsy. PMID- 3105381 TI - Galactorrhea, gynecomastia, and hypothyroidism in a man. PMID- 3105382 TI - [Association of bacterial endocarditis and alcoholic cirrhosis in 9 patients]. AB - Ten cases of bacterial endocarditis were observed in cirrhotic patients. In 7 cases, endocarditis was due to group D Streptococcus, 5 of which were Streptococcus D. bovis. Special features were the involvement of tricuspid valve and the involvement of two or more valves in 4 cases. Surgery was necessary in the acute phase in 5 patients: cure was definitely obtained in 8 cases after a particularly long interval. A colonic lesion could have been the portal of entry in some cases. Liver cirrhosis was considered as a predisposing factor for bacterial endocarditis, especially due to group D Streptococcus or to other bacteria of intestinal origin. This is probably related to the frequency of the colonic origin of group D Streptococcus endocarditis. Loss of filter function of the liver may partly explain the features of these forms of endocarditis. PMID- 3105383 TI - The role of thrombin in transcellular metabolism of eicosanoids. PMID- 3105385 TI - Neurofibromatosis. PMID- 3105384 TI - Neurofibromatosis. A review of the clinical problem. AB - NF is a relatively common genetic disorder which predisposes to a variety of clinical manifestations involving multiple body systems. NF poses important questions to researchers involved with developmental neurobiology, nerve regeneration and growth, the mechanism of malignant degeneration, and the use of molecular techniques to identify genetic disorders. It is hoped that this conference will bring together researchers who have developed new techniques in these areas and will encourage them to apply these techniques to the problem of NF. PMID- 3105386 TI - Nerve growth factor modification of the ethylnitrosourea model for multiple schwannomas. AB - The administration of ethylnitrosourea (ENU) to pregnant rats late in gestation or to neonatal rats results in the induction of Schwann cell tumors in a high percentage of perinatally exposed animals. Exogenous administration of nerve growth factor (NGF) significantly reduces the number of Schwann cell tumors and other neurogenic tumors developing in ENU-treated rats. Administration of antibodies directed against NGF prior to neonatal ENU exposure results in a substantial increase in the incidence of Schwann cell tumors, particularly in the trigeminal nerves of both rats and mice. Transplacental ENU treatment causes early neoplastic proliferation (ENP) at 90 days of age in the Schwann cell population of trigeminal nerves in nearly all exposed rats. A variety of NGF treatment protocols (single or multiple inoculations or microinfusion prior to or following ENU exposure) resulted in a significant reduction in ENU-induced ENP in trigeminal nerves. These results indicate that NGF may convey protection either directly or indirectly, by an unknown mechanism, to Schwann cells and other supportive neural cells by reducing their sensitivity to ENU-induced neoplastic transformation. PMID- 3105387 TI - The malformative central nervous system lesions in the central and peripheral forms of neurofibromatosis. A neuropathological study of 22 cases. AB - The neuropathological features of 22 autopsied cases of NF have been reviewed, with special reference to the malformative and proliferative lesions implicating the intracranial and intraspinal neural structures. Eleven cases represented examples of the central form of the disease, and 11 examples of the peripheral form. The central form is defined by the association and multiplicity of cranial and spinal meningeal, nerve-sheath, and glial neoplasms (astrocytomas and ependymomas). Bilateral acoustic schwannomas are a frequent, but not invariable, component of the disease. Central NF is also characterized by the very frequent incidence (9 out of 11 cases) of distinctive malformative CNS lesions, which included intramedullary and perivascular schwannosis, meningioangiomatosis, discrete ependymal ectopias, atypical glial cell nests in the grey matter, and, less frequently, syringomyelia. Many of these hamartomatous changes were closely associated topographically with florid neoplastic lesions. Five of the 11 cases of peripheral NF showed involvement of the CNS by cellular proliferative changes that included subependymal gliofibrillary nodules in 3 cases (causing aqueduct stenosis in 2, with resulting hydrocephalus in 1); hyperplastic meningioencephalic gliosis involving the pons and the cerebellum in 1 case; and micronodular capillary and arteriolar proliferations typical of the vascular form of NF in 1 case. Whereas some of the glial proliferations are probably hamartomatous in nature, others may represent an abnormal productive neuroglial response to adjacent pathological conditions, such as antecedent cerebral hemorrhage or infarct, known to stimulate a proliferative gliosis. Such a response may exhibit morphological features that are indistinguishable from those of an astrocytoma, including leptomeningeal and perivascular invasion. The incidence of proliferative CNS lesions in both the central and the peripheral form of NF indicates that the spectrum of tissues implicated extends beyond those derived solely from the neural crest. PMID- 3105388 TI - Pathology of nerve sheath tumors. PMID- 3105389 TI - Growth-promoting factors in neurofibroma crude extracts. AB - Crude extracts of neurofibromas from two unrelated neurofibromatosis (NF) patients were prepared by mincing, homogenizing, and ultracentrifugation in the absence of added solvents. Explant cultures of neurofibromas from other NF patients were grown at low density in culture medium with and without neurofibroma extract supplementation. Differences in growth were monitored by comparing monolayer densities, colony counts, or uptake of [3]H-thymidine. A consistent enhancement of growth rate was demonstrated, and titration curves showed an increasing effect with increasing dosage (ranging from 1.5 microliter/ml to 25 microliters/ml). However, the extract could not substitute for fetal bovine serum. As determined by microscopic examination of Giemsa stained petri dishes, small spindle-shaped cells, distinct in morphology from ordinary fibroblasts, were the overwhelmingly predominant cell type in most extract-treated cultures. While the specific identity of the growth factor(s) involved is unknown, the following may be stated: The presence of one or more growth factors that may act in an autocrine or paracrine manner in neurofibromas in vivo is demonstrated. There is a preferential effect of such a factor on spindle-shaped cells (presumably Schwann cells), allowing for the selective enrichment of these cells in vitro. There is an enhanced yield of clones derived from single cells, allowing further analysis of the cellular heterogeneity of neurofibromas at the biochemical and molecular levels. These considerations should help to distinguish between those models for neurofibroma growth that emphasize secondary somatic mutations (including allelic exclusion) on the one hand, and cellular interaction on the other hand. PMID- 3105390 TI - Basement membrane proteins produced by Schwann cells and in neurofibromatosis. AB - Mouse Schwann cells and rat RN22 schwannoma cells cultured in the absence of neurons and fibroblasts produce typical basement membrane proteins. Heparan sulfate proteoglycan (low density form), nidogen, and protein BM-40 were identified by radioimmunoassays, immunoblotting, and by immunoprecipitation after metabolic labeling. The cells also produce a laminin-like protein that differs from authentic laminin by a reduced A chain content and lack of antigenic determinants located in the long arm of laminin. Laminin possessing A and B chains is, however, produced by PYS-2 teratocarcinoma cells grown under the same conditions. Laminin from Schwann cell culture medium promotes neurite outgrowth, and this activity could be immunoprecipitated but not blocked by various antibodies against authentic laminin. In addition, Schwann cell laminin is found complexed noncovalently with nidogen. Sulfate incorporation revealed the synthesis of proteoglycans and entactin. A similar set of proteins and in addition collagen IV could be demonstrated in neurofibroma tissue by immunohistology, and were localized to the laminae densae of the multilayered basement membranes around Schwann cells and capillaries. Laminin purified from 0.5 M NaCl neurofibroma tissue extracts possessed both A and B chains. Nidogen was identified in a partially degraded form. PMID- 3105391 TI - Collagens in neurofibromas and neurofibroma cell cultures. AB - Neurofibromas contain approximately 30-50% collagen of their lipid-free dry weight, which is about half of the value of skin but approximately twice that described for peripheral nerve endoneurium. Immunohistochemical stainings indicate that neurofibromas contain types I, III, IV, and V collagens and fibronectin. Most of the neurofibroma cells are type IV collagen and S-100 protein positive, which provides immunohistochemical evidence that neurofibromas are mostly composed of Schwann cell-like cells. The proteoglycan/collagen ratio is 4 to 10 times higher in the neurofibromas than in the surrounding dermal tissue. This would explain the typical soft consistency of the neurofibromas and may contribute to a favorable milieu for tumor growth. Pure fibroblastic cell cultures are obtained from neurofibromas after repeated passages. The cultured cells synthesized type I and III collagens and fibronectin, indicating that these cells are important in the production of the fibrous connective tissue proteins in neurofibromas. PMID- 3105392 TI - Connective tissue biochemistry of neurofibromas. PMID- 3105393 TI - Genetic linkage analysis of neurofibromatosis. PMID- 3105394 TI - On the natural history of von Recklinghausen neurofibromatosis. PMID- 3105395 TI - Genetic linkage analysis of neurofibromatosis with DNA markers. PMID- 3105396 TI - Oncogene expression in neurofibromatosis. AB - To investigate the role of oncogenes in malignancies characteristic of neurofibromatosis, oncogene transcripts were quantitated in a neurofibrosarcoma and in control tissue from a patient with hereditary neurofibromatosis. Sis and N ras were moderately hyperexpressed, raf, Blym, and erbA were slightly hyperexpressed, and abl, erbB, fes/fps, fgr, fos, mos, myb, myc, N-myc, rasHarvey, rasKirsten, ros, src, and yes were not hyperexpressed in the tumor compared to the control tissue. Although additional tumors will be assayed before conclusions are possible, it may be significant that the two oncogenes most hyperexpressed are prior suspects for a pathogenetic role in tumors of the nervous system. PMID- 3105397 TI - Sensitivity of cultured skin fibroblasts from patients with neurofibromatosis to DNA-damaging agents. AB - Neurofibromatosis (NF) is an autosomal dominant disorder associated with various constitutional abnormalities as well as a striking predisposition for malignant and nonmalignant neoplasms, both in cells originating in and not originating in the neural crest. We have examined the sensitivity of cultured skin fibroblasts from patients with neurofibromatosis to several types of DNA damage. Fibroblasts in Dulbecco's modified Eagle's medium were plated at 10(2) to 2 X 10(4) cells per 75 cm2 tissue culture plates, and exposed to various doses of gamma radiation (leads to DNA scission), actinomycin D (a DNA intercalating agent), or mitomycin C (a bifunctional alkylating agent leading to DNA cross-links). Cells were reincubated for 15 to 40 days until surviving colonies exhibited greater than 30 50 cells. Plates were then stained with 1% methylene blue and the colonies counted, with surviving fraction determined relative to plating efficiency. Nine skin fibroblast cell strains from normal individuals were studied as controls. One neurofibromatosis (NF) cell strain, SB23, exhibited normal sensitivity to all three DNA-damaging agents studied in early (7-8) and middle (12-13) in vitro passage. Strain GM0622, on the other hand, exhibited normal sensitivity to the three DNA-damaging agents studied at early passage, but showed a significant decrease in survival after exposure to both gamma radiation (D0 = 106 rad) and actinomycin D (D0 = 0.024 mcg/ml) with increasing passage. Strain GM1639 exhibited decreased survival after actinomycin D exposure at early passage (D0 = 0.017 mcg/ml), with normal survival after exposure to gamma radiation and mitomycin C at the same passage. Cell strains exhibited decreasing low density plating efficiencies and growth rates with increasing passage such that study of cytotoxicity was not feasible after middle passage in strains SB23 and GM0622, and after early passage in strain GM1639. The results suggest that cultured fibroblast cell strains from patients with NF exhibit early in vitro senescence which sometimes is associated with an inability to handle certain DNA-damaging agents. PMID- 3105398 TI - Evidence against linkage of von Recklinghausen neurofibromatosis and chromosome 19 markers. AB - In this paper we report the study of the segregation of three chromosome 19 markers known to be linked to myotonic dystrophy in nine families with von Recklinghausen neurofibromatosis. Clear evidence against linkage was found for all three markers excluding the von Recklinghausen neurofibromatosis gene from the myotonic dystrophy region of chromosome 19. PMID- 3105399 TI - Cell culture studies on neurofibromatosis (von Recklinghausen). Characterization of cells growing from neurofibromas. PMID- 3105400 TI - Hormonal modulation of Schwann cell tumors. I. The effects of estradiol and tamoxifen on methylnitrosourea-induced rat Schwann cell tumors. PMID- 3105401 TI - Neurofibromatosis. A genetic epidemiologist's point of view. PMID- 3105402 TI - Clinical diagnosis of von Recklinghausen's neurofibromatosis. PMID- 3105403 TI - Neurofibromatosis in the bicolor damselfish (Pomacentrus partitus) as a model of von Recklinghausen neurofibromatosis. PMID- 3105405 TI - Neurofibromatosis and cancer. PMID- 3105404 TI - The genetic aspects of neurofibromatosis. AB - Although the genetic pattern in NF has been definitely established as autosomal dominant, more precise data regarding penetrance, natural history, prevalence, and heterogeneity are needed for the counseling of families. NF is the prototypic disorder for the study of the biologic mechanisms of variable expressivity. The widely cited prevalence figure of Crowe is probably too high; thus the mutation ratio estimation in NF is among the highest in man but close to other common Mendelian disorders. With the existing data on frequency of Lisch nodules and with future prospective date on cafe-au-lait spot development, an age-of-onset penetrance curve for NF could be constructed for genetic counseling purposes. The segmental form of NF is of interest as cases of this presentation may be helpful in studying the hypothesis of human somatic mutation when DNA analysis is available. Guidelines for routine evaluation and ongoing health supervision of individuals with neurofibromatosis need to be developed; multidisciplinary NF clinics and collaborative study groups are appropriate settings for this undertaking. Neurofibromatosis is an important disorder for the study of the psychodynamic processes that families experience in dealing with uncertainty. PMID- 3105406 TI - Early family influences on suicidal behavior. PMID- 3105407 TI - Endogenous Bacillus cereus panophthalmitis. AB - Over the past seven years we have treated three cases of drug abusers in whom endogenous Bacillus cereus endophthalmitis rapidly progressed to panophthalmitis. Ocular features of infection with this organism include severe pain, chemosis, proptosis, corneal infiltration and ring abscess, subretinal exudation, retinal hemorrhages, and perivasculitis. The process becomes fulminant in an explosive manner and may be accompanied by fever and leukocytosis. Ophthalmologists should be cognizant of the apparent susceptibility of drug abusers to Bacillus cereus infections and should consider this organism in any severe, rapidly evolving intraocular infectious process. PMID- 3105408 TI - N1 latency prolongation in the guinea pig cochlea treated with nitrogen mustard-N oxide studied by narrow band analysis. AB - The effect of nitrogen mustard-N-oxide (NMO) upon the click and tone burst-evoked N1 latency was examined in 14 albino guinea pigs. In all animals except one, the pseudothresholds of action potentials were elevated, especially in the high tone area. In addition to the amplitude reduction, the N1 latency was prolonged in 12 animals. The narrow band analysis of N1 revealed that the latency was equally prolonged in all frequency areas, although the amount of the amplitude reduction was much larger in the high frequency area. It was concluded that the prolongation of the N1 latency in NMO-treated animals was due to dysfunction of outer hair cells along the entire cochlear partition. PMID- 3105409 TI - [Biochemical, pharmacological and therapeutic aspects of skin metabolism of arachidonic acid]. PMID- 3105410 TI - [17 beta-estradiol receptors in Schistosoma mansoni. Contribution to the explanation of the protective power of this hormone in Schistosoma mansoni bilharziasis in the mouse. Preliminary study]. AB - According to some of our experiments, in adult Schistosoma mansoni, the existence of receptors able to bind the molecules of 17 beta-estradiol might explain the protective power of this hormone in the experimental Schistosoma mansoni parasitosis in the mice and in the hamster. PMID- 3105411 TI - A nutrition team is not essential for optimal parenteral nutrition therapy. PMID- 3105412 TI - Polydioxanone suture in the gastrointestinal tract. AB - A randomized prospective trial was undertaken of polydioxanone suture (PDS) versus conventional suture material in 98 patients undergoing anastomoses in the gastrointestinal tract. Nine patients died within 6 months of surgery, one of these being related to an anastomotic leak. All other patients were followed up for between one and three and a half years. In 57 colonic anastomoses, 30 were randomized to a single layer of 2/0 (BPC) interrupted PDS and 27 to a single of 2/0 (BPC) interrupted silk. Follow up sigmoidoscopy and barium enemas were used to confirm the clinical suspicion of 6 benign anastomotic strictures, 5 of which occurred in the PDS group. At this stage, the colonic arm of the trial was discontinued because the 19% stricture rate with PDS was deemed unacceptable. In a second limb of the study, patients were randomized to two layers of 2/0 (BPC) continuous PDS or 2/0 (BPC) continuous chromic catgut. There were no significant differences in 32 gastric or small bowel anastomoses and in particular, no anastomotic strictures were apparent. The reasons for the high rate of stricture formation when using PDS for large bowel anastomoses are unclear. However, it would seem to be a suitable alternative to chromic catgut when confined to the stomach and small intestine. PMID- 3105413 TI - The surgical treatment of a pharyngeal pouch: inversion or excision? AB - Twenty eight patients with pharyngeal pouches were treated at the Radcliffe Infirmary, Oxford, between 1975 and 1985. Nineteen of these patients had the pouch excised and 9 patients had the pouch inverted. Preoperative and postoperative cine barium swallows were obtained on all patients. The results show pouch inversion to be an effective method of treatment with a low recurrence rate, and fewer complications compared with pouch excision. Inversion of a pharyngeal pouch with a cricopharyngeal myotomy is therefore recommended as a safe, satisfactory treatment. PMID- 3105414 TI - Visual processing in monkey extrastriate cortex. PMID- 3105415 TI - [Coronarography-scintigraphy comparison of the effects of trinitrin-spray in 15 patients with coronary disease]. AB - 15 patients with coronary disease underwent a dual investigation, angiographic and scintigraphic, first without treatment and after administration of 0.8 mg of sub-lingual trinitrin-spray. The radiocinema angiography enables to explore variations of the coronary and stenosic diameter, the duration of the opacification (inverse of circulatory velocity) and the tonality of the network. Plane scintigraphy with T1201 enables to quantify the regional fixation in 9 myocardiac territories, as well as the global fixation with the myocardium/background noise ratio and the index of mean perfusion deficit. The diameter of healthy arteries and the pre- and post-stenotic segments of the diseased arteries are uniformly dilated after trinitrin (11.5-12.5%) while the stenoses are on an average unchanged (+ 1.2% NS). 4 cases of stenotic dilatations were observed, but without any decrease of the degree of stenosis (the pre stenotic diameter increasing in the same proportions), nor any scintigraphic improvement. On scintigraphy, no difference of the myocardium/background noise ratio nor the mean deficit index was observed after trinitrin, which demonstrates the non-variation of the total coronary output. On the contrary, a redistribution of the regional activity (and therefore of the regional coronary flow) is observed in 10 patients. In comparing the stenotic areas which improve on scintigraphy (group I) and those which do not improve or deteriorate (group II) with the modifications of the arterial diameters under trinitrin, a correlation does not appear to be present. Also, the tonality is uniformly increased in both groups. The circulatory velocity is, however, significantly decreased in group II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105416 TI - [Flecainide by the intravenous route: a new method for decreasing auricular fibrillation]. AB - The action of intravenous flecainide was studied in patients presenting a tachyarrhythmia secondary to a permanent atrial fibrillation of recent onset. We obtained 9 improvements in 15 patients included in the protocol which consisted in the intravenous injection of 2 mg/kg of flecainide in 10 minutes. The side effects were minimal: no sign of cardia insufficiency nor alteration of the arterial blood pressure was noted. Nevertheless, although interesting, this method to decrease atrial fibrillation is not, in our opinion, destined to replace external electrical shock, except in some special cases. PMID- 3105417 TI - Postmortem endocrine levels in the vitreous humor. AB - The vitreous humor and sera from 51 autopsy cases were assayed for progesterone, estradiol, thyroxine, triiodothyronine, TSH, FSH, LH and prolactin. The results indicate that the blood retinal barrier has unique properties of its own. All hormones were measurable in the sera. Progesterone, estradiol, T3 and T4 were not detected despite their lipid solubility and their small molecular size while the larger glycoprotein hormones were easily measureable. PMID- 3105418 TI - Toxicity and pathological effects of a new dosage form of mitomycin C for carcinomatous peritonitis. AB - A new dosage form (MMC-CH) of mitomycin C (in a suspension of activated carbon adsorbing mitomycin C in saline), designed for intracavitary use in carcinomatous peritonitis, was studied for its toxicity and pathological effects in rats. The LD50 values determined with the Litchfield-Wilcoxon's method in three types of MMC-CH were 7.6 (100 micrograms/ml MMC and 0.5 mg/ml activated carbon in saline), 16.5 (100 micrograms/ml MMC and 0.75 mg/ml activated carbon in saline), and more than 25 mg/kg (100 micrograms/ml MMC and 1 mg/ml activated carbon in saline), while in mitomycin C solution the value was 3.05 mg/kg. The lethal toxicity decreased with the change of dosage form. Studies on survival, symptoms of intoxication and macroscopic and microscopic examinations of autopsied animals revealed that there was no evidence of any additional side effects produced by the change of dosage form. PMID- 3105419 TI - Augmentation of spontaneous cytotoxicity of human lymphocytes by RU 41.740 is due to monocyte-derived factors distinct from interleukin 2, interferon alpha and gamma. AB - In vitro exposure of human blood lymphoid cells to RU 41.740 (Biostim), a glucoprotein extract of Klebsiella pneumoniae, augments spontaneous cytotoxicity of the lymphocytes. It was observed that the augmentation could be blocked by inhibitors of RNA- and protein-synthesis, but not by an inhibitor of DNA synthesis. The increased cytotoxicity of Biostim-treated cells could not be explained by an increased proportion of lymphocytes binding to the target cells (K562). This indicates that Biostim acts by increasing the lytic activity of lymphocytes rather than by increasing the expression of target cell recognition structures. Further, it was shown that culture supernatants of Biostim-exposed monocytes, but not purified lymphocytes, contain factors that augment cytotoxicity of purified lymphocytes. This finding is in line with the previously reported monocyte-dependence of Biostim-induced augmentation of lymphocyte cytotoxicity. Interleukin-2 (IL-2) activity was not observed in supernatants of Biostim-exposed lymphoid cells and augmentation of lymphocyte cytotoxicity could not be inhibited by antibodies directed against interferon (IFN) alpha or gamma. This indicates that Biostim stimulates monocytes to liberate factors other than IL-2 or IFN which augment spontaneous cytotoxicity of lymphocytes. PMID- 3105420 TI - Long-term clinical assessment of pulpotomies with calcium hydroxide containing Ledermix in human permanent premolars and molars. PMID- 3105421 TI - Employer-based disability management and rehabilitation programs. PMID- 3105422 TI - Theory testing research: methodological issues. PMID- 3105423 TI - Contraceptive behavior. PMID- 3105424 TI - Policy for health? PMID- 3105425 TI - Health care policy, values, and nursing. AB - Dominant American values of individualism, competition, and inequality shape American health care policy. Nurses must critically analyze these basic value premises. This can be done by addressing two major flaws in American health care policy creation. First, health care policies are separated from politics and economics. Second, incremental policies are supported bereft of an analysis of their limitations and the need for structural changes if America is to have a humane and equitable health care system. PMID- 3105426 TI - Nursing, health, and policy within a community context. AB - This article describes a method of linking curriculum and the nursing role in health policy. Graduate students participated in a project to assess the impact of policy on the health of a community and the implications for nursing. The experience of this project indicates that learning about policy within a community context has merit for helping students understand the impact of policy on nursing. PMID- 3105427 TI - Deinstitutionalization of the mentally ill: oversimplification of complex issues. AB - Deinstitutionalization is the predominant public mental health policy in most states. An analysis of this policy in one state from a political-economic perspective gives support to the hypothesis that deinstitutionalization results in a two-class system of mental health care based upon the client's ability to pay. Inequalities exist in opportunities for care that are appropriate for the pathology suffered by the chronically mentally ill, and patients' basic needs are often unmet. Corporate actors involved in developing mental health policy overpower clients as well as nurses in the distributive process. The impact of this policy on quality of care and nursing is significant. PMID- 3105428 TI - Nursing ethics in an age of controversy. AB - Nursing ethics is examined within the context of the health care controversy concerning care v cure. Yarling and McElmurry's contention that nursing ethics should focus on autonomy and reform is critically appraised. In opposition, the moral sense of nursing practice is affirmed as the primary focus of nursing ethics. Reform concerns enhancing excellence in nursing within an expanding legitimate authority. The "in-between" situation of nurses is regarded as an excellent position from which to foster communal decisions by teams of health care workers engaged in the moral practice of fostering the well-being of the ill. PMID- 3105429 TI - Patient classification and resource allocation in Veterans Administration nursing homes. AB - Patient classification for Veterans Administration and non-Veterans Administration long-term care patients is discussed. Results are reported from 290 patients in two VA nursing homes by using both resource utilization groups and an independently generated classification system. Patient classes were generated by using the Automatic Interaction Detection Program, which was the methodology used to create the diagnosis related groups. The use of diagnoses in long-term care patient classification is also reviewed. The effect of disaggregated nursing times by type of provider and by type of nursing activity on patient classes is examined. PMID- 3105430 TI - An analysis of the liability insurance crisis. AB - The problem of the growing liability insurance crisis is examined from historical, economic, policy, and legislative perspectives. Specifics of arguments presented by physicians, nurses, lawyers, and insurers are provided to illustrate the conflict inherent in the situation. Reports of policy actions accomplished by these groups are presented with a discussion of related bills proposed in past years. Specific nurse populations directly affected by the insurance crisis are presented and actions to be taken by nurses and legislators to deal with the problem are suggested. PMID- 3105431 TI - [Comparative evaluation of the antibacterial activity of aminoglycosides by means of microcalorimetry]. AB - Possible use of microcalorimetry for comparative investigation of antibiotics is exemplified by estimation of the kinetics of the antibacterial effect of netilmicin, sisomycin and gentamycin sulfate on moderately sensitive strains of E. coli and P. aeruginosa. It is suggested that the area under the curve of the kinetics of the rate of heat release by the bacterial cultures in the presence of antibiotics be used as a parameter characterizing the integral antibacterial effect. The parameter was used for demonstrating the differences in the antibacterial action of netilmicin, sisomycin and gentamycin sulfate on the strains tested with application of various inoculum sizes and antibiotic concentrations. PMID- 3105432 TI - [Effect of lysine on cephalosporin biosynthesis and morphogenesis in Acremonium chrysogenum]. AB - The effect of exogenic lysine on production of cephalosporin by auxotrophic and prototrophic strains of A. chrysogenum and their development was studied. It was shown that lysine added to the medium at a concentration of 0.5 or 1 mg/ml partially eliminated the effect of catabolic repression by glucose and had a stimulating effect on production of cephalosporin in the presence of sucrose. Both phenomena were most pronounced in the prototrophic strain 309-A. High concentrations of lysine (10 mg/ml) inhibited cephalosporin biosynthesis more intensively in the auxotrophic strain 291-A than in the prototrophic strain 309 A. Marked differences in the character of the culture development in media supplemented with 1 or 10 mg/ml of lysine were also observed. PMID- 3105433 TI - [Principles for analyzing the kinetic curves of the antimicrobial effect in dynamic systems simulating the pharmacokinetic profiles of antibiotics]. AB - Alternative variants of the available methods for estimating the antimicrobial effect kinetics in the in vitro dynamic systems were analyzed. For defining and analyzing the concentration-effect relations in the in vitro dynamic systems it was recommended that two integral parameters characterizing the antimicrobial effect duration (TE) and intensity (IE) irrespective of the recording means be used. TE is defined by the time from the moment of antibiotic administration into the dynamic system till the moment when the count of the microorganisms reaches again its initial level. IE is defined by the area between the curves of the microbial growth kinetics in the presence and absence of an antibiotic. The possible application of TE and IE is exemplified by relation between the sisomicin antimicrobial effect on P. aeruginosa 58, E. coli 93 and K. pneumoniae 5056 and the antibiotic concentration under conditions of sisomicin pharmacokinetic profiles reproduction after intramuscular administration within the levels of the therapeutic doses with an account of individual variability of the aminoglycoside concentration in the blood of humans. PMID- 3105434 TI - [Methodological characteristics of the use of the immunofluorescence method for the rapid determination of the sensitivity of the anthrax microbe to antibiotics]. AB - An immunofluorescent method for rapid assay of antibiotic sensitivity of Bacillus anthracis was tested with the use of virulent strains. It was shown that the immunofluorescent method was applicable for assay of antibiotic sensitivity of Bacillus anthracis immediately upon inoculation of the native matter: soil samples and other materials. Comparison of the results obtained with the method of serial dilutions and the immunofluorescent method showed that the levels of the Bacillus anthracis sensitivity to rifampicin, benzylpenicillin, tetracycline, streptomycin and gentamicin coincided. The immunofluorescent method provided the results on antibiotic sensitivity of Bacillus anthracis 6-8 hours after initiation of the rapid assay, the inoculum size being at least 10(6) spores/ml. Isolation of the causative agent pure cultures was not required. Under laboratory conditions the assay required consideration of the characteristic features of the causative agent and fixation of smear replicates in a mixture of 96 degrees ethyl alcohol and 3 per cent hydrogen peroxide for 30 min. After the assay the panels should be disinfected by immersing for 16-18 hours into 6 per cent hydrogen peroxide supplemented with 0.5 per cent of a detergent. PMID- 3105435 TI - [Microbiological methods of pharmacokinetic research on chemotherapeutic (antibacterial and antitumor) preparations]. AB - Microbiological methods are the most accessible in clinical assay of drug concentrations in biological fluids. When a sensitive test system is available and the requirements for collection and investigation of the materials are observed such methods are applicable in studies of pharmacokinetics of both antibacterial and antitumor drugs. PMID- 3105436 TI - [Fusion of Streptococcus lactis protoplasts]. PMID- 3105437 TI - [Assessment by the material and energy balance method of the directed biosynthesis of riboxin by altering the external culture conditions]. AB - The effect of various agitation conditions on growth of the cell population of Bacillus subtilis and production of riboxin was studied. The physiological state of the culture was estimated by the relations for the respiration coefficient CO2/O2, the yield of the constructive metabolism products (X + P) by oxygen Yx + p/O2, the ratio of consumed glucose to ammonium nitrogen S/NH4+, the coefficient of the cell biosynthetic activity Yp/x and the parameter of the energetic efficiency of the substrate usage (eta). It was shown that the maximum biosynthetic activity was mainly defined by the culture state in the trophophase. The growth of the cell population in this case should proceed under conditions of conjugated aerobic metabolism. It was found that directed biosynthesis of riboxin could be provided by changing the cultivation conditions and estimation of the culture physiological state by the parameters of the material and energy balance. PMID- 3105438 TI - In vitro susceptibility of gram-positive cocci to paldimycin. AB - Paldimycin (U-70138F) is a new antimicrobial agent with activity against gram positive cocci. Clinical isolates of staphylococci and streptococci were tested. MICs were higher in Mueller-Hinton broth than in nutrient broth. Change in pH had minimal effect on the MICs in either broth. When inoculum size was varied, an inoculum effect was observed. The gram-positive cocci tested were generally more susceptible to paldimycin than to vancomycin. PMID- 3105439 TI - Early effects of beta-lactams on aminoglycoside uptake, bactericidal rates, and turbidimetrically measured growth inhibition in Pseudomonas aeruginosa. AB - In vitro studies of tircarcillin or cefsulodin combined with [3H]tobramycin were performed with Pseudomonas aeruginosa. The rate of bacterial killing, the uptake of tobramycin, and the effects on optical density were measured. Both beta lactams increased the uptake of subinhibitory concentrations of tobramycin. This result was quantitatively associated with a 2- to 4-h time-kill potentiation and confirmed earlier studies on the mechanism of beta-lactam-aminoglycoside synergy in Escherichia coli (P. H. Plotz and B. D. Davis, Science 135:1067-1068, 1962). PMID- 3105440 TI - Effect of acetyl salicylic acid on production and action of leukocyte-derived interferons. AB - Although acetylsalicylic acid does not itself induce interferon, acetylsalicylic acid was found to significantly enhance the production of both human alpha interferon and human gamma interferon when added with the appropriate inducers to cultures of human peripheral blood mononuclear cells. The mechanisms associated with this effect were investigated. PMID- 3105441 TI - In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium avium, Mycobacterium fortuitum, and Mycobacterium chelonae to ticarcillin in combination with clavulanic acid. AB - The in vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium avium, Mycobacterium fortuitum, and Mycobacterium chelonae (M. chelonei) to ticarcillin in combination with calvulanic acid (CA) was studied by the agar dilution method. All the M. tuberculosis, M. bovis, and M. africanum strains were inhibited at a ticarcillin concentration of 32 micrograms/ml or lower in combination with 5 micrograms of CA. M. chelonae and M. avium strains proved resistant to more than 128 micrograms of ticarcillin plus 5 micrograms of CA per ml. M. fortuitum strains needed 128 micrograms of ticarcillin plus 5 micrograms of CA to inhibit approximately 30% of the isolates. PMID- 3105443 TI - Pharmacokinetics and plasma bactericidal activity of aztreonam in low-birth weight infants. AB - Aztreonam (30 mg/kg) was administered intravenously every 12 h during week 1 and every 8 h during weeks 2 to 4 of life to 26 low-birth-weight (less than 2,000 g) infants, and plasma concentration-time curves were measured on two occasions. The pharmacokinetics were described equally well by one-compartment and noncompartment models, and the values on day 1 were similar to those measured during the steady state on days 3 to 6. The mean peak plasma concentrations at completion of the 10-min infusion were from 65 to 83 micrograms/ml, the higher concentrations being seen in the larger infants. The half-lives of aztreonam ranged from 5.4 to 8.6 h and did not change significantly with birth weight. The median peak and trough plasma bactericidal titer against a strain of Escherichia coli (MBC, 10 micrograms/ml) was 1:16. Against a strain of Pseudomonas aeruginosa (MBC, 16 micrograms/ml), the median peak and trough bactericidal titers were 1:8 to 1:16 and 1:4, respectively. The urinary concentrations of aztreonam on day 1 of therapy were from 24 to 460.7 micrograms/ml (mean +/- 1 standard deviation, 254 +/- 113 micrograms/ml). PMID- 3105442 TI - Characterization of impermeability variants of Pseudomonas aeruginosa isolated during unsuccessful therapy of experimental endocarditis. AB - We characterized five amikacin-resistant variants of Pseudomonas aeruginosa isolated from aortic valve vegetations during unsuccessful therapy of experimental endocarditis. These organisms were cross resistant to other aminoglycosides. No aminoglycoside-modifying enzymes were produced by these strains. However, all five variants demonstrated significant defects in permeability and intracellular uptake of [3H]amikacin when compared with the amikacin-susceptible parental strain (0 to 26% of that of the parental strain; mean, approximately 15%). The permeability defects were unstable in vitro, with normalization after serial passage in antibiotic-free media. The variants grew as nonpigmented, small-colony types, with in vitro generation times approximately 1.5 to 2 times longer than that of the parental strain (30 to 40 versus 20 min, respectively). Two impermeability variants were compared with the parental strain for ability to induce experimental endocarditis in rabbits with aortic catheters. Both variants were virulent in vivo; however, mean bacterial densities in vegetations were approximately 2.5 log10 CFU/g lower in animals challenged with the variants than in animals challenged with the parental strain, probably reflecting a slower in vivo growth rate. PMID- 3105444 TI - Silver-coated nylon fiber as an antibacterial agent. AB - A blend of nylon fiber and silver-coated nylon fiber (the latter known as X static) was used in these experiments. This fiber was bactericidal when bacteria were exposed to it directly or to an extract derived from its prior incubation in salt solution. At ambient temperatures, a rapid exponential decrease of survival occurred, usually after a delay of approximately 1 h. The rate of killing (decrease of survival) increased with an increase in X-static percentage of the fiber blend, temperature of fiber extraction, concentration of Tris buffer present during extraction, and temperature at which bacteria were exposed to the extract. When bacteria were exposed to the extract at 37 degrees C as opposed to ambient temperature, there was no delay in onset of killing. Escherichia coli was generally the indicator organism tested, but comparable results were also found for Pseudomonas, Klebsiella, Staphylococcus, and Streptococcus species. The rate of killing increased with increasing silver ion concentration of the fiber extract, as determined through atomic absorption spectrophotometry. The rate of killing was greater and the onset was earlier with an extract containing silver ions from fiber than with a salt solution containing the same concentration of silver ions from silver nitrate. Studies of the kinetics of ion release suggested that X-static may be an effective, sustained-release antibacterial agent. PMID- 3105446 TI - Pharmacokinetics and tissue penetration of Ro 23-6240, a new trifluoroquinolone. AB - A 400-mg dose of the trifluorinated quinolone Ro 23-6240 was administered orally to each of six healthy male volunteers, after which the concentrations of this agent in serum and cantharidin-induced inflammatory fluid were measured. Absorption was rapid, with a mean peak level in serum of 6.1 micrograms/ml, which was attained 0.71 h after administration. The elimination half-life in serum was 11.95 h. The agent penetrated the inflammatory fluid rapidly; the percent penetration was 89.7%. Urinary recovery of Ro 23-6240 was 58.6% by 72 h. PMID- 3105445 TI - Continuous-infusion ampicillin therapy of enterococcal endocarditis in rats. AB - Intermittent administration of ampicillin alone has resulted in high failure rates in previously described animal models of enterococcal endocarditis. We developed a rat model of enterococcal endocarditis which permits comparison of continuous intravenous infusion of ampicillin with intramuscular therapy. Continuous low-dose ampicillin infusion (450 mg/kg [body weight] per day) was compared with the same dose given intramuscularly in three divided doses and with high-dose infusion (4.5 g/kg per day) of the drug. For the infecting strain of Streptococcus faecalis, the MIC and MBC were 1 microgram/ml. Mean ampicillin levels in serum were 53.9 +/- 4.8 (peak) and less than 1 (trough), 8.7 +/- 1.4, and 244 +/- 29 micrograms/ml for intramuscular, low-dose, and high-dose regimens, respectively. Ampicillin infusion therapy significantly increased the survival rate and sterilization of blood cultures. Continuous infusions were superior to intermittent therapy in eradicating bacteremia. After 5 days of treatment, low dose ampicillin infusion was more effective than intermittent therapy in sterilizing cardiac vegetations (P less than 0.01). Continuous-infusion therapy at either dose was significantly more effective than intramuscular injection in reducing bacterial titers in cardiac vegetations (5.4 +/- 1.0 log10 CFU/g [low dose], 4.8 +/- 0.3 log10 CFU/g [high dose], and 7.7 +/- 0.3 log10 CFU/g [intramuscular]). However, no statistically significant advantage was found for high-dose compared with low-dose ampicillin infusion in lowering bacterial titers in vegetations (P greater than 0.3). PMID- 3105447 TI - Alterations in peptidoglycan of Neisseria gonorrhoeae induced by sub-MICs of beta lactam antibiotics. AB - Exposure of Neisseria gonorrhoeae to sub-MICs of selected beta-lactam antibiotics caused distortion of normal cell morphology. Analysis of the peptidoglycan indicated that the cells were accumulating increased quantities of disaccharide pentapeptide in their cell walls. The O-acetylated form of the disaccharide pentapeptide was not detected among the major peaks. The correlation of antibiotic binding to gonococcal penicillin-binding protein 2 and accumulation of non-O-acetylated disaccharide pentapeptide suggested an explanation for the previously observed relationship of penicillin-binding protein 2 and O acetylation of peptidoglycan. PMID- 3105448 TI - In vitro evaluation of tigemonam, a novel oral monobactam. AB - Tigemonam, a novel, orally administered monobactam, exhibited potent and specific activity in vitro against members of the family Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae. Its activity was variable to poor against gram-positive bacteria, Acinetobacter spp., Pseudomonas aeruginosa, and anaerobes. Within its spectrum of activity, tigemonam was far superior to oral antibiotics currently available, including amoxicillin-clavulanic acid, cefaclor, and trimethoprim-sulfamethoxazole. In addition, tigemonam was superior to cefuroxime, which is under development as an oral pro-drug, and more active than cefixime against several genera of the Enterobacteriaceae. The activity of tigemonam against the enteric bacteria, Haemophilus species, and Neisseria species was, in general, comparable to that of the quinolone norfloxacin. The excellent activity of tigemonam against beta-lactamase-producing bacteria reflected its marked stability to hydrolysis by isolated enzymes. The expanded spectrum of activity against gram-negative bacteria observed with tigemonam thus extends oral beta-lactam coverage to include members of the Enterobacteriaceae that are intrinsically or enzymatically resistant to broad-spectrum penicillins and cephalosporins. PMID- 3105449 TI - BMY 28100, a new oral cephalosporin. AB - BMY 28100, a new oral cephalosporin with a (Z)-propenyl side chain at the 3 position and a p-hydroxyphenylglycyl substituent at the 7 position, was evaluated in comparison with cefaclor and cephalexin and, when appropriate, ampicillin and vancomycin. In vitro, BMY 28100 was more active than the reference cephalosporins against streptococci, Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes, Haemophilus influenzae, Propionibacterium acnes, Clostridium perfringens, and Clostridium difficile. BMY 28100 was comparable to cefaclor and more active than cephalexin against Staphylococcus saprophyticus and ampicillin susceptible strains of Branhamella catarrhalis; but against ampicillin-resistant strains of B. catarrhalis, BMY 28100 was comparable to cephalexin and more active than cefaclor. Against Neisseria gonorrhoeae, BMY 28100 was comparable to cephalexin, but less active than cefaclor. Members of the family Enterobacteriaceae overall were equally susceptible to BMY 28100 and cefaclor but were less susceptible to cephalexin. In human serum, BMY 28100 was 45% protein bound. After an oral dose to mice, 82% of the drug was recovered in urine. The oral therapeutic efficacy of BMY 28100 in systemically infected mice reflected its activity in vitro. PMID- 3105450 TI - Role of beta-lactamase in in vivo development of ceftazidime resistance in experimental Pseudomonas aeruginosa endocarditis. AB - Two ceftazidime-resistant variants of Pseudomonas aeruginosa (PA-48, PA-60), obtained from cardiac vegetations of rabbits with endocarditis receiving ceftazidime therapy, were studied for mechanisms of resistance. Both resistant variants were stably derepressed for the type Id beta-lactamase, which was ceftazidime inducible in the parental strain (PA-96) used to initially infect the rabbits. There was no evidence of ceftazidime bioinactivation by the resistant strains, and their outer membrane permeabilities were comparable to those of the parental strain. No alterations were observed in patterns of outer membrane proteins or membrane lipopolysaccharides in the resistant variants as compared with the parental strain. Penicillin-binding protein patterns of the resistant variants revealed the absence of penicillin-binding protein 4 in both, with acquisition of a new protein of higher apparent molecular weight in PA-60. Calculation of the rate of appearance of ceftazidime in the periplasm at sub-MICs suggested that slow enzymatic hydrolysis of the beta-lactam, rather than nonhydrolytic trapping, was the major explanation for the induced resistance in vivo in strains PA-48 and PA-60. PMID- 3105452 TI - In vivo synergism of roxithromycin (RU 965) and interferon against Toxoplasma gondii. AB - We investigated the activity of roxithromycin (RU 965) and gamma interferon alone and in combination in a murine model of toxoplasmic encephalitis. Roxithromycin at a dosage of 35 or 50 mg per mouse per day decreased mortality. Gamma interferon alone significantly prolonged time to death. When combined, the two agents were remarkably synergistic. PMID- 3105451 TI - In vitro activity of CGP 31608, a new penem. AB - The in vitro activity of CGP 31608, a semisynthetic penem derivative, was compared with that of Sch 34343, imipenem, cefoxitin, cefuroxime, and ceftazidime and other beta-lactams, when appropriate, against 628 recent isolates and other beta-lactam-resistant strains. The MICs of CGP 31608 against 90% of the members of the family Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria spp., Bacteroides spp., Clostridium spp., staphylococci, and Streptococcus pneumoniae were between 0.25 and 8 micrograms/ml. The susceptibility of beta-lactamase-producing strains and known porin mutants of the Enterobacteriaceae suggests that CGP 31608 is resistant to many important beta lactamases (including the mutationally derepressed chromosomal enzymes) and is not excluded from the bacterial cell in strains expressing these known porin mutations. Generally, CGP 31608 was less active than imipenem, Sch 34343, and the cephalosporins, except against Pseudomonas aeruginosa. The activity of CGP 31608 against Staphylococcus aureus (including methicillin-resistant strains) was greater than that of the cephalosporins. The major target site in Escherichia coli K-12 for CGP 31608 was penicillin-binding protein 2. The serum protein binding of 5 micrograms of CGP 31608 per ml was 14%, and serum had little effect on activity. PMID- 3105453 TI - Simple method for screening aflatoxin-producing molds by UV photography. AB - UV absorption by aflatoxins was monitored in GY agar medium by UV photography. In the UV photographs, aflatoxin-producing molds were identified as gray or black colonies, whereas aflatoxin-nonproducing molds appeared as white colonies. By cellophane transplantation experiments and silica gel thin-layer chromatography, the products absorbing UV light substantially were found to be mainly aflatoxins B1 and G1 excreted from the mold mycelium into the agar medium. UV absorption did not occur when the agar medium contained aflatoxin-noninducible carbon sources instead of glucose. Various inhibitors of aflatoxin production, such as dichlorovos and dimethyl sulfoxide, also decreased the intensity of UV absorption. These results indicate that this technique can be used as a simple, safe, and rapid method of screening aflatoxin-producing molds. PMID- 3105454 TI - Transformation of toluene and benzene by mixed methanogenic cultures. AB - The aromatic hydrocarbons toluene and benzene were anaerobically transformed by mixed methanogenic cultures derived from ferulic acid-degrading sewage sludge enrichments. In most experiments, toluene or benzene was the only semicontinuously supplied carbon and energy source in the defined mineral medium. No exogenous electron acceptors other than CO2 were present. The cultures were fed 1.5 to 30 mM unlabeled or 14C-labeled aromatic substrates (ring-labeled toluene and benzene or methyl-labeled toluene). Gas production from unlabeled substrates and 14C activity distribution in products from the labeled substrates were monitored over a period of 60 days. At least 50% of the substrates were converted to CO2 and methane (greater than 60%). A high percentage of 14CO2 was recovered from the methyl group-labeled toluene, suggesting nearly complete conversion of the methyl group to CO2 and not to methane. However, a low percentage of 14CO2 was produced from ring-labeled toluene or from benzene, indicating incomplete conversion of the ring carbon to CO2. Anaerobic transformation pathways for unlabeled toluene and benzene were studied with the help of gas chromatography-mass spectrometry. The intermediates detected are consistent with both toluene and benzene degradation via initial oxidation by ring hydroxylation or methyl oxidation (toluene), which would result in the production of phenol, cresols, or aromatic alcohol. Additional reactions, such as demethylation and ring reduction, are also possible. Tentative transformation sequences based upon the intermediates detected are discussed. PMID- 3105455 TI - Increased susceptibility and reduced phytoalexin accumulation in drought-stressed peanut kernels challenged with Aspergillus flavus. AB - Three genotypes of peanut (Arachis hypogaea L.), with ICG numbers 221, 1104, and 1326, were grown in three replicate plots and drought stressed during the last 58 days before harvest by withholding irrigation water. Within each plot there were eight levels of stress ranging from 1.1 to 25.9 cm of water. Kernels harvested from the plots were hydrated to 20% moisture and challenged with Aspergillus flavus. Fungal colonization, aflatoxin content, and phytoalexin accumulation were measured. Fungal colonization of non-drought-stressed kernels virtually ceased by 3 days after inoculation, when the phytoalexin concentration exceeded 50 micrograms/g (fresh weight) of kernels, but the aflatoxin concentration continued to rise exponentially for an additional day. When fungal colonization, aflatoxin production, and phytoalexin accumulation were measured 3 days after drought stressed material was challenged, the following relationships were apparent. Fungal colonization was inversely related to water supply (r varied from -0.848 to -0.904, according to genotype), as was aflatoxin production (r varied from 0.876 to -0.912, according to genotype); the phytoalexin concentration was correlated with water supply when this exceeded 11 cm (r varied from 0.696 to 0.917, according to genotype). The results are discussed in terms of the critical role played by drought stress in predisposing peanuts to infection by A. flavus and the role of the impaired phytoalexin response in mediating this increased susceptibility. PMID- 3105456 TI - Conjugal transfer of nisin plasmid genes from Streptococcus lactis 7962 to Leuconostoc dextranicum 181. AB - Acriflavine-generated mutants of Streptococcus lactis 7962 with various combinations of plasmid molecular masses were screened for nisin production. Nisin was produced by both the wild type and mutants that contained a 17.5 megadalton plasmid, which was obscured by chromosomal fragments. No nisin was produced by plasmid-free mutants. Sucrose fermentation and nisin production were simultaneously expressed. A transconjugant obtained from nisin-producing donor S. lactis 7962 and recipient Leuconostoc dextranicum 181 was a "supernisin" producer. The L. dextranicum Nis+ transconjugant was resistant to S. lactis 7962 phage and vancomycin (greater than 1,000 micrograms/ml), and it contained an extra 17.5-megadalton plasmid. PMID- 3105457 TI - Microorganisms capable of metabolizing the herbicide metolachlor. AB - We screened several strains of microorganisms and microbial populations for their ability to mineralize or transform the herbicide metolachlor [2-chloro-N-(2-ethyl 6-methylphenyl)-N-(2-methoxy-1-methylethyl)-acetami de] because such cultures would potentially be useful in the cleanup of contaminated sites. Although we used various inocula and enrichment culture techniques, we were not able to isolate microorganisms that could mineralize metolachlor. However, strains of Bacillus circulans, Bacillus megaterium, Fusarium sp., Mucor racemosus, and an actinomycete were found to transform metolachlor. Several metabolites could be determined with high-performance liquid chromatography. The tolerance of the strains to high concentrations of metolachlor was also evaluated for the usefulness of the strains for decontamination. Tolerance of the actinomycete to metolachlor concentrations over 200 ppm (200 micrograms/ml) was low and could not be increased by doubling the sucrose concentration in the growth medium or by using a large biomass as inoculum. However, a Fusarium sp. could grow and transform metolachlor up to a concentration of 300 ppm. PMID- 3105458 TI - Salt tolerance of lactose-grown Vibrio parahaemolyticus carrying Escherichia coli lac genes. AB - Lac- strains of Vibrio parahaemolyticus were converted to Lac+ on receiving a hybrid plasmid containing the lactose utilization genes of Escherichia coli K-12. A V. parahaemolyticus strain containing this hybrid plasmid exhibited optimal growth rates on glucose and other carbon sources in the presence of 0.2 to 0.4 M NaCl. Growth of the same strain on lactose was inhibited at similar concentrations of NaCl. The altered growth rate responses in lactose medium appeared to be attributable to effects of NaCl on the activity of lactose permease, and possibly on that of beta-galactosidase, rather than on the levels of these enzymes in V. parahaemolyticus cells. PMID- 3105459 TI - Alteration of poly(adenosine diphosphoribose) metabolism by ethanol: mechanism of action. AB - We present evidence that ethanol alters intracellular poly(adenosine diphosphoribose) metabolism and we further describe the mechanism by which ethanol exerts its effect on polymer synthesis. One percent ethanol stimulates polymer accumulation as much as 2.5-fold but does not alter polymer degradation in intact cells following DNA damage. Ethanol directly stimulates polymer synthesis following low doses of DNA damage induce by deoxyribonuclease I in a nucleotide-permeable cell system that does not possess a functional polymer turnover system. Ethanol has no measurable effect on polymer synthesis in undamaged nucleotide-permeable cells or in permeable cells treated with high doses of deoxyribonuclease I. Ethanol concentrations that stimulate poly(adenosine diphosphoribose) polymerase activity in vitro specifically lower KDNA without affecting KNAD or Vmax. The results clearly show that ethanol alters the binding of this enzyme to the DNA component of chromatin and that this altered binding is responsible for the activation of the enzyme. Altered affinity of poly(adenosine diphosphoribose) polymerase and perhaps other regulatory proteins for chromatin may play an important role in the pathology of alcohol. PMID- 3105460 TI - [Research related to hormones in Nagase analbuminemic rats]. AB - The levels of hormones in the anterior pituitary gland and serum in Nagase analbuminemic rats (NAR) were examined. For the anterior pituitary gland, the contents of prolactin, TSH, GH, LH and FSH in male NAR were lower than those of normal rats. In female NAR, prolactin and TSH levels were also lower than those in normal rats, whereas LH, FSH and GH were unchanged. In serum, the concentrations of TSH, T3, T4, estradiol, testosterone and prolactin (female only) were examined. The serum prolactin level in female NAR was lower than that of normal rats, whereas a higher level of serum TSH was seen in NAR. Male NAR had a higher T3 level and a lower T4 level. Although the estradiol concentration in male NAR was normal, the serum testosterone level was only a quarter of that in normal rats. We investigated the reason for the low level of serum testosterone in male NAR through biochemical studies on steroid metabolism. The results indicated that the low serum concentration of testosterone in NAR was mainly attributable to decreased biosynthesis of testosterone in the testes. Prolactin is the primary hormone for experimental mammary tumorigenesis. In association with the lower prolactin level in female NAR, induction of tumors by 7, 12 dimethylbenz (a) anthracene (DMBA) was studied. NAR showed a significantly lower mammary tumor response to DMBA. The incidences of spontaneous mammary tumor in NAR and normal rats after 2 years were also compared. The incidence was much lower in NAR than in the controls. Thus the lower mammary tumor induction in NAR could mostly be ascribed to the lower level of circulating prolactin. PMID- 3105461 TI - [Studies on the new antibiotic kazusamycin and related substances]. AB - Kazusamycins A and B and leptomycin B have a structure characteristic of an unsaturated, branched-chain fatty acid with a terminal delta-lactone ring, and show antibacterial activity on some kinds of fungi. Kazusamycin A (KZM-A) showed cytotoxic activity on mammalian cells at very low concentrations (ng/ml) in vitro. The antibiotic inhibited not only the growth of transplantable murine tumors and their metastases to the lung but also human mammary tumors inoculated into nude mice. KZM-A became immediately distributed to the main organs of mice, and a certain quantity of the antibiotic was inactivated by binding to high molecular-weight substances such as albumin. A large quantity of KZM-A was carried to the liver and excreted into the bile, but was then reabsorbed by the small intestine. The growth of tumor metastases (L5178Y cells) in the liver was suppressed by KZM-A. The antibiotic induced severe diarrhea by causing necrosis and/or lysis of the mucous membrane of the small intestine. In contrast to this, the degree of myelotoxicity was relatively slight. The active site of the fatty acid of KZM-A appeared to consist of conjugated double bonds, carboxylic acid and hydroxyl moieties. PMID- 3105462 TI - [UFT therapy of experimental gastric cancer in beagles induced by ENNG]. AB - Therapeutic effects and dynamics of UFT were studied using beagles with ENNG induced gastric cancers. Nine canine subjects confirmed to have gastric cancers by punch biopsy under gastrofiberscopy were divided into 3 group given 5 mg/kg/day of UFT for 101 days, 7.5 mg/kg/day for 67 days and 12 mg/kg/day for 45 days, respectively. Although the extent of macroscopic change revealed by gastrofiberscopy was minor, one of the dogs in the third group did show a Grade II b effect according to the criteria of Histopathological Effects on Cancer Tissues by Chemotherapy proposed by Oboshi and Shimozato. Animals were sacrificed by bleeding 4 hours after the last administration of anticancer agent and concentration of 5-FU and tegafur in the serum and each organ were determined. It was recognized that the concentration of anticancer agent in gastric cancer tissue was higher than that in neighboring normal gastric tissue. PMID- 3105463 TI - [Direct and indirect antitumor effect of murine recombinant interferons]. AB - The antitumor effects of murine recombinant interferons (beta) and (gamma) against B-16 melanoma and B16-F10 melanoma were examined. In a pharmacokinetic study, intraperitoneal injection of Mu-rIFN (gamma) produced higher and longer detectable IFN activity than administration of Mu-rIFN (beta) in both plasma and organs. In clonogenic assay, Mu-rIFN (gamma) at 1,000 units/ml showed 80% inhibition of colonies of B16-F10 melanoma. However, Mu-rIFN (beta) hardly inhibited the colony formation of B16-F10 melanoma. Furthermore, both IFNs had different characteristics from each other in the augmentation of NK cell and macrophage activities. In the experimental metastasis of B-16 melanoma, the inhibitory effect of Mu-rIFN (beta) on the pulmonary metastasis was mediated by the host defense mechanism, and NK cells and macrophages were important for the inhibition. Mu-rIFN (gamma) showed a stronger effect against B16-F10 melanoma in the inhibition of the growth of sc implanted tumor and artificial metastasis. PMID- 3105464 TI - [Enhancement of the antitumor effect on Walker-256 of administration of noradrenaline in physiological saline for five minutes after intraarterial injection of MMC]. AB - An experimental study was performed on the enhancement of cytotoxic damage to a tumor by ischemia during chemotherapy. An antitumor effect was obtained by 10 minute ligation of the hindpaw of Wistar rats bearing implanted Walker-256 at four days before, and after administration of MMC into the same femoral artery. The injection of 0.5 microgram/ml of noradrenaline in physiological saline into the tumor-feeding artery at a rate of 1 ml/min for 5 minutes after intraarterial administration of MMC produced the same degree of improved antitumor effect as that observed in the 10-minute ligation therapy. PMID- 3105465 TI - [Treatment of renal cell carcinoma invading the inferior vena cava; role of preoperative targeting chemotherapy]. AB - Locally invasive carcinoma of the kidney, prognosis of which still remains unsatisfactory, is a therapeutic challenge in uro-oncology. Our recent experience has indicated that mitomycin C microcapsule therapy which is introduced as a prototype of intravascular targeting chemotherapy is an effective preoperative adjuvant in terms of improving the prognosis of locally invasive kidney carcinoma. Two cases with huge kidney carcinoma directly invading into the caval wall were presented. They were initially considered inoperable, but repeated microcapsule therapy for 5 months provided substantial tumor reduction and facilitated radical operation. The patients are tumor-free at 2 and 8 year after the treatment respectively. The role of targeting chemotherapy in the treatment of locally invasive carcinoma was discussed. PMID- 3105467 TI - [The problems of postoperative adjuvant chemotherapy in gastric cancer]. AB - We studied the survival rate and state of recurrence of histologically curatively resected cases in the 1st (Method II) and the 2nd studies of the Cooperative Study Group of Surgical Adjuvant Chemotherapy for Gastric Cancer. The administration of MMC combined with Futraful was most effective, but there was no difference of survival rate between the patients in the 1st study given Futraful for 3 months and those in the 2nd study given the drug for 12 months. Irrespective of the kind of drug and term of administration, cases with stage I showing recurrence within 2 years after surgery accounted for ca. 50% of all stage I cases recurring within 5 years. In spite of histological malignancy, cases with stage II showing recurrence within 2 years after surgery accounted for ca. 65% of all stage II cases recurring within 5 years. As to the recurrent hazard rate for each recurrent type of case with stage III, all types showed a high peak between 0.5 and 1.5 years after surgery. The peritoneal metastatic hazard rate was the highest. The hazard rates for Groups B (MMC + Futraful) and C (Futraful) were lower than those for Group A (MMC). The above findings suggest the importance of postoperative adjuvant chemotherapy, which is performed repeatedly and intensively for 2 years in order to prevent recurrence. PMID- 3105466 TI - [Application of cytopathology in a sensitivity test for anti-tumor agents. I. An experimental study]. AB - Although the human tumor clonogenic assay (HTCA) is extremely reliable in determining clinical correlations, it is a complicated process requiring considerable time in order to obtain results. Thus, an experimental study on cytopathologic observation (cytologic assay) and comparative evaluation between it and HTCA were performed in order to establish a more rapid and accurate drug sensitivity test. Materials included Colon 26, a cell line established in our department, malignant effusion and surgical specimens. In carrying out HTCA according to the Hamburger-Salmon method, the cell suspension samples following exposure to anti-tumor agents (MMC, L-PAM, ADM, CDDP) were cultivated in test tubes for 3-8 hours and stained by the Papanicolaou and Giemsa methods. According to Tokita's criteria, when cellular changes showed as nuclear pyknosis and nuclear destruction were found to have increased significantly in comparison with a control group, the cells were judged to be sensitive. Very similar and parallel results were obtained between HTCA and cytologic assay in this study, with a significant correlation. Cytologic assay was proved to be an easy, rapid and accurate method for testing drug sensitivity and its clinical application can be expected in the future. PMID- 3105468 TI - [Subrenal capsule assay for chemosensitivity testing]. AB - The subrenal capsule (SRC) assay for cancer chemotherapy was tested according to Bogden's methodology. Of 37 patients providing tumor tissue for assay, 29 cases were considered suitable for evaluable assays. Fourteen patients had clinically evaluable diseases and 10 cases were evaluable for SRC assays. Correspondence between sensitive assay and clinical sensitivity was seen in 2 cases, and that between resistant assay and clinical resistance was seen in 4 cases. Discordance between sensitive assay and clinical resistance was seen in 4 cases. In histological studies, cancer tissues implanted in the subrenal space in immunocompetent mice did not show marked proliferation and were replaced by prominent leukocyte infiltration and fibrosis on day 6 after inoculation. The degree of leukocyte infiltration in the xenografts in the mice administered some anti-cancer drugs was slight in comparison with that in untreated control mice, which showed a remarkable trend in xenografts treated with 5-fluorouracil and cyclophosphamide, respectively. Our study suggests that there are many problems involved in the SRC assay methodology of Bogden, and that careful examination of this aspect will be required. PMID- 3105469 TI - [Intravesical chemotherapy with interferon in superficial bladder tumors]. AB - Interferon (IFN) was used in the treatment of superficial bladder tumors. Interferon (IFN-beta, IFN-gamma) was instilled into the bladder at dosages ranging from 16 billion to 36 billion U IFN per 30 ml physiological saline. The IFN was instilled into the bladder once a day or twice a day for 10 to 20 days. In this trial, ten patients with superficial bladder tumors were treated at Okayama City Hospital, and of these, 1 CR, 3 PR, 2 MR and 4 NC were obtained. There were no signs of either irritable bladder or general side effects. IFN (especially IFN-beta) is considered a useful drug for superficial bladder tumors in intravesical chemotherapy. PMID- 3105470 TI - [Three cases of adenocarcinoma of the lower esophagus and cardia showing marked regression after radiotherapy with FT-207]. AB - Three cases of adenocarcinoma of the lower esophagus and cardia which is considered to be difficult to control by radiotherapy alone, were given radical irradiation combined with FT-207 suppository. Dosages of radiation and FT-207 were 70 Gy/35 f and 1.5 g/day (1 case) or 1.0 g/day (2 cases), respectively. The treatment was successful locally; dysphagia was improved in all cases and 1 case has shown no recurrence for a period of two and a half years. Side effects were leukopenia and hemorrhagic esophagitis in the case given 1.5 g/day of FT-207, but these were cured by conservative therapy. These results emphasize that radiotherapy combined with anticancer drugs should be considered as a local therapy for inoperable adenocarcinoma of the lower esophagus and cardia. PMID- 3105471 TI - Treatment of refractory supraventricular arrhythmias with flecainide acetate. AB - We treated 13 children aged 0.2 years to 15.7 years (median 7.1 years) with flecainide acetate for refractory symptomatic supraventricular tachycardia. Six children had direct atrioventricular accessory pathways, of whom four had overt Wolff-Parkinson-White syndrome on the 12 lead electrocardiogram, while in the other two the accessory pathway was concealed. Three children had nodal atrioventricular re-entrant tachycardia, two had a re-entrant tachycardia, the exact mechanism of which was not known, one child had ectopic atrial tachycardia, and one had atrial flutter associated with an atrial septal defect. The remaining 12 children had structurally normal hearts. Flecainide (2 mg/kg intravenously) resulted in termination of the tachycardia in 11 of the 12 children treated during tachycardia. In 11 of the children successful prophylaxis was achieved with oral flecainide. Side effects occurred in two children during intravenous administration, but there were no side effects with oral treatment. This experience indicates that flecainide, which has not been used extensively in children, is an effective and safe antiarrhythmic agent, capable of terminating and controlling supraventricular tachycardia in children. Furthermore, flecainide may be successful where conventional agents fail. PMID- 3105472 TI - Nebulised sodium cromoglycate and verapamil in methacholine induced asthma. AB - Fifteen children with asthma underwent challenges with methacholine on separate days after double blind administration by nebuliser of either verapamil (5 mg), cromoglycate (20 mg), or saline (placebo). The provocation doses that produced a 20% fall in forced expiratory volume in one second (PD20) were analysed. There was variation in the protective effects of verapamil and cromoglycate among the patients. Although cromoglycate produced an increase in PD20 in 53% of the children tested, the protection was not significant when compared with the placebo. Verapamil was partially protective, however, in 80% of children and achieved significantly better results than the placebo. We suggest that this is likely to be due to a direct effect on bronchial smooth muscle. PMID- 3105473 TI - Mastocytoma induced by cigarette smoke particulates: "cigarette tar". AB - Cutaneous mastocytomas were observed in female CD-1 mice following long-term application of three types of cigarette smoke condensate suspensions ("tars") from different cigarettes or of 7,12-dimethylbenz(a)anthracene (DMBA) and tetradecanoylphorbol-acetate (TPA) or tars. These mastocytomas were always accompanied by diffuse dermal mast cell infiltration (DDMI). These results indicate that mastocytomas were induced by agents present in the cigarette smoke condensate of DMBA plus TPA. PMID- 3105474 TI - Spironolactone in the treatment of hirsutism. AB - Spironolactone was used in 90 hirsute women because of its antiandrogenic effect. The drug was administered twice daily from the 4th to the 22nd day of six cycles (total dosage was 200 mg per day). The results suggest that spironolactone is suitable for the treatment of hirsutism. PMID- 3105475 TI - alpha-Difluoromethylornithine inhibits the first part of exoerythrocytic schizogony of Plasmodium berghei in rodents. PMID- 3105477 TI - Suppression of shivering decreases oxygen consumption and improves hemodynamic stability during postoperative rewarming. AB - Thirty-three patients undergoing elective myocardial revascularization were prospectively randomized into two study groups (Group S and Group P) to permit evaluation of the effects of shivering on oxygen consumption per minute (VO2), carbon dioxide production per minute (VCO2), and hemodynamic performance. Group S was allowed to shiver during the postoperative rewarming period, and Group P received hourly injections of pancuronium bromide and Metubine (metocurine) sulfate with sedation to block the shivering response. Group S demonstrated significantly higher increases in VO2 and VCO2, lower systolic blood pressure and mixed venous oxygen saturation, and a greater use of inotropic support than the patients in Group P. Suppression of the shivering response minimized increases in VO2 and VCO2, improved hemodynamic stability, and resulted in a decreased need for inotropic support. PMID- 3105476 TI - Fatty acid and glycerol kinetics in septic patients and in patients with gastrointestinal cancer. The response to glucose infusion and parenteral feeding. AB - The rates of glycerol and free fatty acid (FFA) kinetics in normal volunteers (VOL), non-weight-losing (NWL) gastrointestinal cancer patients, weight-losing (WL) gastrointestinal cancer patients, and in severely septic patients, using constant infusions of d-glycerol and 1-13C palmitic acid; were determined. Rates of FFA oxidation have also been quantitated. Measurements were made in the basal state, during glucose infusion (4 mg/kg/min), and during total parenteral nutrition (TPN). Rates of glycerol and FFA appearance (Ra) in volunteers and NWL cancer patients were similar, and in both groups there was a significant suppression after glucose infusion. The basal Ra values for glycerol and FFA were 2.4 +/- 0.2 and 6.5 +/- 0.8 mumol/kg/min, respectively, in the volunteers, and in the NWL cancer patients the corresponding values were 2.7 +/- 0.4 and 7.1 +/- 1.1 mumol/kg/min (not significantly different). Compared with the volunteers, the rates of glycerol and FFA turnover were significantly elevated in both septic patients and WL cancer patients. The values for glycerol and FFA Ra were 6.3 +/- 1.1 and 13.1 +/- 3.0 mumol/kg/min, respectively, in the septic patients. The corresponding values were 4.1 +/- 0.4 and 11.7 +/- 1.6 mumol/kg/min in the WL cancer patients. In contrast to the response seen in the volunteers and NWL cancer patients, glucose infusion did not suppress lipolysis in either the septic or WL cancer patients. In all groups studied, glucose infusion resulted in an increase in FFA recycling. Despite the fact that the WL cancer patients had an increased FFA availability, they were significantly less able to oxidize either endogenous FFA or infused lipid when compared with NWL cancer patients (the basal % of FFA uptake oxidized in WL cancer patients was 10 +/- 2% vs. 18 +/- 3% in NWL cancer patients). In contrast, the septic patients had an enhanced capacity to oxidize either endogenous FFA or infused lipid (the basal % of FFA uptake oxidized was 40 +/- 8%, and during TPN this increased in 65 +/- 10%). From these studies the following was concluded: in terms of lipid kinetics, NWL cancer patients are not significantly different from volunteers; WL cancer patients and septic patients have elevated rates of lipolysis, and in contrast to what was seen in NWL cancer patients and in volunteers, glucose infusion in WL cancer patients and in septic patients does not result in a significant inhibition of lipolysis; and WL cancer patients have an impaired capacity to oxidize either endogenous FFA or infused lipid.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3105478 TI - [Advances in ablative methods of fulguration]. PMID- 3105479 TI - [Percutaneous transluminal aortic valvuloplasty using a balloon catheter. A new therapeutic option in aortic stenosis in the elderly]. AB - Aortic valvular dilatation with a balloon catheter was performed in 44 patients, 20 men and 24 women, most of whom were very elderly (average age 77 years). The indication for valvular replacement had not been retained in these cases because of surgical contra-indications or a very high operative risk and in 3 cases because of patient refusal. Twenty-nine patients were in functional classes III or IV of the NYHA classification; 12 had syncopal episodes and 18 had invalidating angina. The dilatation was performed by a femoral arterial approach in 34 cases, and by a brachial arterial approach in 10 cases. MEDI-TECH catheters with 15, 18 or 20 mm diameters when inflated were used in the majority of cases. Several inflations lasting 10 to 240 seconds were performed in each case with balloons of increasing size. This was well tolerated in all but one patients who had a sharp syncope. The immediate results confirmed valvular dilatation. The average transvalvular pressure gradient fell from 76 +/- 25 mmHg to 30 +/- 13 mmHg (p less than 0.001). The aortic valve surface area calculated by the Gorlin formula increased from 0.5 +/- 0.18 cm2 to 1 +/- 0.42 cm2 (p less than 0.01). After dilatation the gradient was less than or equal to 40 mmHg in 37 cases; aortic valve surface area was greater than or equal to 1 cm2 in 14 cases and less than or equal to 0.7 cm2 in only 5 cases. The left ventricular ejection fraction increased immediately after valvuloplasty from 44 +/- 16 p. 100 to 49 +/- 15 p. 100 (p less than 0.01). In the 18 cases in which it was less than 40 p. 100 before valvuloplasty, it increased from 30 +/- 6 p. 100 to 36 +/- 9 p. 100 (p less than 0.02). Residual aortic regurgitation was only observed in one case. Two patients died in the hospital period (4.6 p. 100). There were no other serious complications. During an average follow-up period of 60 days (3 weeks to 6 months) there was a big improvement in symptoms in the great majority of cases and, in particular, syncopal and anginal attacks disappeared. Only 4 patients remained in functional classes III or IV after valvuloplasty. Percutaneous aortic valvuloplasty is a new, relatively simple, low risk, economic and very effective therapeutic procedure in all cases in which aortic valve replacement is contra indicated or refused by the patient.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3105480 TI - [Reoperations in valve surgery. Apropos of 194 cases]. AB - Between 1970 and 1985, 194 patients underwent one or several reoperations after conservative valvular surgery (Group A) or valvular replacement surgery (Group B). Group A: comprised 141 patients with a previous history of closed heart mitral commissurotomy (114 cases), open heart mitral commissurotomy (20 cases), mitral valvuloplasty (5 cases) or aortic commissurotomy (2 cases) reoperated after an average period of 153 +/- 44 months. At reoperation, prosthetic valve replacement of the previously operated valve was systematic and another valvular procedure was also performed in 66 cases. Hospital mortality was 7.8 p. 100. Mortality was high in patients reoperated in functional Class IV of the NYHA classification, after closed heart mitral commissurotomy performed over 10 years before hand. The global mortality rate was 17 p. 100 (average postoperative follow-up of 70 +/- 44 months). The actuarial 5 year survival rate was 85 +/- 6 p. 100 and the 10 year survival was 70 +/- 13 p. 100; NYHA Class IV cardiac failure was a significant poor prognostic factor (p less than 0.05). The prognosis of reoperation after commissurotomy depended mainly on the interval between the relapse of symptoms and reoperation. Group B: comprised 53 patients with valvular prostheses reoperated after an average period of 58 +/- 41 months. The indications of reoperation were prosthetic valve dysfunction (31 cases), perivalvular leak (5 cases), prosthetic valve thrombosis (6 cases), infective endocarditis (7 cases), haemolysis (1 case) and associated valvular disease (10 cases). Reoperation concerned mechanical prostheses in 26 cases and bioprostheses in 24 cases. It consisted in valvular replacement (51 cases) or reinsertion (2 cases). Eight patients underwent second reoperation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105481 TI - [Anti-tachycardia radiofrequency pacemakers. Experience with 44 cases]. AB - Programmed cardiac stimulation may be performed externally using implanted radiofrequency receiving capsules. Between 1979 and 1984, 44 patients underwent implantation of these devices, 12 with atrial leads for supraventricular tachycardias (8 orthodromic reciprocating tachycardias, 1 intranodal junctional tachycardia and 3 atrial tachycardias), and 32 with ventricular leads for ventricular tachycardias. In the first case the transmitter was given to the patients so that they could terminate the tachycardias themselves. In the second case, the transmitter was kept in the cardiology department. All patients were also prescribed prophylactic antiarrhythmic drugs. The radiofrequency method was effective in 11 out of 12 cases of supraventricular tachycardia with a follow-up period ranging from 24 to 65 months (average 45 +/- 11 months). In the ventricular tachycardia group, the device was used in 11 patients to terminate ventricular tachycardia and in all patients to evaluate the efficacy of the antiarrhythmic therapy by provocative programmed stimulation with a follow-up ranging from 2 to 81 month (average 24 +/- 20 months). This palliative therapeutic method has reduced the number of hospital admissions in these patients. The indications are relatively few because of the efficacy of currently available antiarrhythmic agents and the possibility of radical treatment of tachyarrhythmias by surgery or catheter ablation. PMID- 3105482 TI - [Exclusive permanent atrial stimulation. Clinical experience apropos of 65 cases with a follow-up of 1 to 5 years]. AB - The authors report their experience of permanent exclusive atrial pacing in the treatment of sinus node dysfunction in a series of 65 cases with a follow up of 1 to 5 years (average 37.6 months; 2406 patients months), 41 women and 24 men aged 74 +/- 3 years. Sixty one patients were symptomatic. The diagnosis was made from surface ECG recordings in 54 cases (83 p. 100) and after electrophysiological investigation in 11 cases (16 p. 100). Atrioventricular conduction was carefully evaluated before implantation: PR equal to or less than 200 ms, Wenckebach point equal to or greater than 130/min, absence of ventricular pauses longer than 3,000 ms after carotid sinus massage, HV interval equal to or less than 55 ms [measured in 57 cases (87 p. 100)], negative Ajmaline test in 6 patients with intraventricular conduction defects. Performed J-shaped atrial leads with active (66 p. 100) or passive fixations (34 p. 100) were implanted by an endocavitary approach (right subclavian vein in 60 cases: 92 p. 100). There were 3 cases of early lead displacement and one patient developed an elevated threshold of pacing. There were 5 deaths during the follow-up period (3 of cardiovascular origin). The neurological symptoms disappeared in 93 p. 100 of cases. No cases of cardiac failure were observed after permanent pacing. Fifteen patients had documented supraventricular arrhythmias before implantation; 5 patients continued to have the same paroxysmal or permanent arrhythmias but 10 patients had no further recurrences, 8 with and 2 without antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105483 TI - [Intracavitary extraction of fragments of intracardiac catheters using a pigtail catheter. Apropos of 14 operations]. AB - Endocavitary extraction of intracardiac fragments of intravenous catheters was attempted in 14 patients over a 7 year period. The fragments were recovered in 13 cases under local anaesthesia without complications. The average duration of the procedure was less than 15 minutes. The technique requires a pigtail catheter, a material which is usually readily available in all catheter laboratories. This simple procedure may prevent complications and enable some patients to avoid surgery. PMID- 3105484 TI - [Epidemiology of minor electrocardiographic anomalies predictive of the occurrence of ischemic cardiopathy]. AB - Common electrocardiographic manifestations (CEM) are predictors of ischemic heart disease (IHD). If precursors of the disease, their risk factors should be similar to those of IHD. This hypothesis has been assessed on results of multiphasic screening recorded in 1976 and 1981, in 1,347 45-65 year old men. Risk factors are social class (blue collar relative risk rr = 2.3), physical activity at work (sedentariness rr = 2.4), systolic blood pressure, no beer consumption and blood urea nitrogen with an exponential risk curve. Cholesterolemia, smoking, diabetes mellitus, overweight and uricemia are not predictors of CEM incidence within 5 years. These results support the idea that CEM are partially asymptomatic expression of IHD; they also have another significance. Subgroups should be individualized and analysis yielded on larger samples. Correlation analysis has been performed between IHD mortality and beer consumption on basis of French counties. A positive correlation (r = 62, p less than 0.01) is opposed to individual results. PMID- 3105485 TI - [Delayed filling of the anterior interventricular artery. Apropos of 9 cases]. AB - Selective coronary angiography has shown that typical angina pectoris may occur in the absence of atheromatous coronary stenosis. Other causes of these attacks of pain have been found: coronary spasm, small vessel disease, abnormal dissociation of haemoglobin or metabolic disturbances of the myocardial cell. Of all the patients undergoing coronary angiography in 1984 at the Centre Cantini, 9 had no classical coronary lesions but delayed filling of the left anterior descending artery. This syndrome was described for the first time in 1972 by Tambe as the "slow flow velocity syndrome". The aim of this study was to analyse the clinical, ECG and haemodynamic profiles of those patients. Five of them also underwent stress Thallium myocardial scintigraphy. An ergometrine provocation test was performed afterwards under ECG control. Delayed filling was appreciated by comparison with the other vessels and also by measuring the filling time which was two or three times longer than in a control series of 9 patients with angina and normal coronary arteries. The difference was statistically significant. These findings were only observed in strictly normal coronary vessels; they were reproducible and unaffected by the administration of nitrate derivatives. In our series all 9 patients were men with an average age of 51.4 years. One patient was asymptomatic and had a history suggestive of myocardial infarction, and 4 others had typical angina of effort: all had abnormal exercise stress tests. The other 3 patients had spontaneous atypical chest pain, normal resting ECG and a negative exercise stress test (impossible in one case). The five stress Thallium scintigraphies showed myocardial perfusion defects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105486 TI - [Total or partial electrical interruption of the atrioventricular pathway. Evaluation of clinical results and indications]. AB - After checking on the efficacy and innocuity of catheter ablation of the His bundle in an experimental study in the sheep, 22 patients with supraventricular tachycardia resistant to an average of 5.5 +/- 1.7 antiarrhythmic drugs per patient underwent this procedure. The most common arrhythmias were atrial fibrillation or flutter (poorly tolerated in 14 cases), and reciprocating tachycardia (8 cases, including 3 with accessory atrioventricular pathways). In 3 of the 5 patients with intranodal tachycardia, an initial attempt was made to modify one of the two AV nodal conduction pathways. Although complete atrioventricular block was obtained in all patients, atrioventricular conduction returned in 15 patients between the 30th minute and 4th day after the procedure. A second attempt at His bundle ablation was carried out in 9 patients. During follow-up ranging from 1 to 38 months, complete or an advanced degree of atrioventricular block persisted in 5 patients, the other patients being in sinus rhythm (12 cases) or slow atrial fibrillation (2 cases). The remaining patient who was in complete atrioventricular block died of septicaemia 2 months after the procedure. The clinical results were evaluated by electrophysiological investigation, exercise testing and Holter monitoring. There were 15 satisfactory clinical results (83.3 p. 100) and 3 poor results. This series shows that interruption or modification of the normal atrioventricular conduction pathway may be performed at low risk and with good results in a high percentage of cases. It is a valuable therapeutic option in patients with supraventricular tachycardia resistant to antiarrhythmic therapy. PMID- 3105487 TI - [Detection of arterial thrombi using blood platelets labeled with indium-111]. AB - Scintigraphy with Indium 111-labelled platelets was carried out in 62 patients (37 transient cerebral ischaemic accidents, 21 lower limb ischaemic episodes and 4 aortic aneurysms) to detect arterial thrombi. The results of this investigation were compared with the surgical findings and showed this to be a satisfactory method of detecting haematologically active thrombi. PMID- 3105488 TI - [Clinical and developmental aspects of 1-vessel right coronary atheroma. Therapeutic consequences]. AB - This study analysed the clinical profile, prognosis and consequences on left ventricular function of isolated obstructive atherosclerosis of the right coronary artery in order to establish the indications of percutaneous angioplasty. The inclusion criteria were at least one stenotic lesion greater than 75 p. 100 of a dominant or equilibrated right coronary artery and exclusion of stenosis of the other coronary vessels. A questionnaire was sent to the treating physician and to the patient to establish the actuarial survival (Cutler and Ederer's method). The average period of follow-up was 56 months (range 12 to 70 months). Seventy one patients (average age 53 years) were selected from a series of 2,675 consecutive coronary angiograms performed between 1979 and 1984 (2.7 p. 100). The incidence of previous infarction was 60 p. 100; this was located on the inferior wall in 75 p. 100, inferobasal wall in 12 p. 100 and infero-latero-basal wall in 13 p. 100. Bypass surgery was performed in 7 cases and percutaneous angioplasty in 2 cases. Sixty-two cases were managed medically. Analysis of the 71 angiographic films of the series showed in retrospect an indication for percutaneous angioplasty in 29 patients (42 p. 100 of the series). The 5 year mortality rate was 5.6 p. 100. Death was sudden in the 4 cases observed, including one on the 28th day after bypass surgery complicated by perioperative infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105489 TI - [Mitral stenosis with notable or important subvalvular changes. Complete open commissurotomies supported by chorda transfer]. AB - Since 1983, 40 consecutive patients with mitral stenosis (MS) and significant disease of the subvalvular apparatus underwent open heart mitral commissurotomy (OHMC). The aim of the study was to evaluate the effects of an unrestricted dilatation of the two commissures followed by repair of the subsequent mitral regurgitation. The mitral regurgitation created by this procedure in 24 cases was corrected by transferring 2 to 6 chordae tendinae to the free border of the anterior and/or posterior leaflet in the commissural region. A central regurgitant lesion due to lack of coaptation of the valvular surfaces was treated by annuloplasty with a Carpentier prosthesis in 12 cases. The subvalvular abnormalities were treated by the conventional techniques of fenestration, resection and division of the papillary muscles. Thirty of the 38 survivors had no residual murmur, and 6 had a short low intensity systolic murmur. The 2D echocardiographic study showed no residual stenosis. The residual systolic murmurs were evaluated by pulsed Doppler and corresponded to very localised regurgitation. This extensive operative technique gives very good immediate valvular results which, associated with an adequate subvalvular procedure, are considered to be an important prognostic factor. PMID- 3105490 TI - [Intravenous sotalol in the acute treatment of supraventricular tachycardias]. AB - The effects of intravenous sotalol (0.5 mg/kg in 6 minutes) were studied in 23 patients with supraventricular tachycardia (ventricular rate greater than 120 bpm) after failure of placebo (isotonic dextrose). Thirteen patients had atrial flutter or fibrillation and 10 a junctional tachycardia of recent onset. Sinus rhythm was restored in 4 of the patients with atrial flutter or fibrillation and the ventricular rate was slowed significantly in 3 patients (less than 100 bpm). In 3 other patients the ventricular rate decreased (31 to 35 p. 100) but remained above 100 bpm. Sinus rhythm was restored in 3 of the 10 patients with a junctional tachycardia five to twelve minutes after beginning the injection. A slight slowing of the heart rate (13 to 27 p. 100) was observed in the other 7 patients but the frequency remained over 100 bpm. Overall, a satisfactory result was obtained in 10 patients (43 p. 100) including 7 cases in which sinus rhythm was restored. Sotalol was well tolerated in 21 patients; one patient complained of cold in the legs and one patient developed asymptomatic bradycardia (46 bpm). This study shows that intravenous sotalol may be useful in the emergency treatment of supraventricular tachycardia. PMID- 3105491 TI - [Phono-mechanographic evaluation of aortic stenoses. Contribution of the B1 maximum murmur/B1-B2 index]. AB - The diagnostic value of phonomechanography in valvular aortic stenosis was reassessed with a rarely used index, the ratio S1-maximum intensity of the systolic murmur/S1-S2, or Thiron's index, the author of which only studied the correlations with the aortic transvalvular pressure gradient. The results obtained by the author being considered inconclusive, we decided to examine its correlations with aortic valve surface area calculated with the Gorlin's formula. The study was carried out in 38 patients with pure aortic stenosis, in whom 4 phonomechanographic parameters, the corrected left ventricular ejection time (Meiners), the carotid pulse half peak time, the S1-maximum intensity of the murmur interval and Thiron's index, were compared with the transvalvular pressure gradient and the aortic valve surface area at catheterisation. The first two parameters mentioned above were of limited value (correlations with aortic valve surface area r = 0.315, p less than 0.05 and r = 0.477, p less than 0.01 respectively). On the other hand, a good correlation was obtained with Thiron's index (r = 0.624, p less than 0.001) which was better than that found with the interval between S1 and maximum intensity of the systolic murmur (r = 0.483, p less than 0.001) in a population not excluding subjects with cardiac failure. These results indicate that: when Thiron's index less than or equal to 0.45, the aortic stenosis is probably mild (aortic surface area greater than 0.8 cm2), when Thiron's index is 0.46 greater than 0.56, the aortic stenosis is likely to be moderately severe (aortic surface area 0.8 less than 0.5 cm2), when Thiron's index is greater than 0.57, the aortic stenosis is probably severe (aortic surface area less than 0.5 cm2). In our series, Thiron's index was the best phonomechanographic parameter for the assessment of pure aortic stenosis. It could not be calculated in 10 out of 48 patients; this drawback was not encountered with the corrected left ventricular ejection time or the carotid pulse half peak time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105492 TI - [Reliability of automatic oscillometric monitoring of arterial pressure. Effect of hypotension and arrhythmias]. AB - The object of this study was to assess the reliability of automatic oscillometric monitoring of the systemic blood pressure. The trial was carried out in 4 patients in situations including hypotension and attacks of arrhythmia. The oscillometric pressure measured in the arm was compared with the pressure recorded by an intra-radial arterial catheter in the opposite arm. All patients were in the dorsal decubitus position. One hundred and ten comparative measurements were performed with values ranging from 48 to 200 mmHg for the systolic pressure, 36 to 112 mmHg for the diastolic pressure and 40 to 136 mmHg for mean arterial pressure. A satisfactory correlation was found between the two methods in 91 measurements in sinus rhythm with respect to systolic (r = 0.95, p less than 0.001), diastolic (r = 0.93, p less than 0.001) and mean arterial pressures (r = 0.95 p less than 0.001). The average duration of the measurements was 32 +/- 5 seconds. During the study, one patient developed paroxysmal atrial fibrillation during which 19 comparative measurements of the mean pressure were performed. The correlation between the two methods was not as good as that observed during sinus rhythm (r = 0.73, p less than 0.01) and the average duration of measurement increased significantly (44 +/- 14 seconds). A correlative study was also performed during hypotension. This was defined as directly recorded systolic blood pressures of less than 90 mmHg, diastolic pressures less than 60 mmHg and mean pressures of less than 70 mmHg (n = 40).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105493 TI - [Intermittent dysfunction of a Bjork-Shiley tricuspid prosthesis caused by thrombosis suspected through pulmonary scintigraphy]. AB - Thrombosis of a Bjork-Shiley tricuspid valve prosthesis was observed 4 years after its implantation. The resulting dysfunction was intermittent blocking the disc in the closed position leading to recurrent near-syncopal malaises probably due to a temporary fall in cardiac output and cerebral blood flow and a right to left interatrial shunt which was detected at pulmonary scintigraphy performed to exclude pulmonary embolism. The Bjork-Shiley prosthesis was replaced with a Carpentier-Edwards n. 29 prosthesis with a good result after a follow-up of one year. PMID- 3105494 TI - [An unusual protodiastolic bruit: the click of an aberrant mitral cord]. AB - An asymptomatic adult woman without clinical cardiac disease had an unusual early diastolic heart sound. All usual causes of this finding were excluded: it was not a delayed pulmonary component of the second heart sound, a mitral or tricuspid opening snap, an early diastolic third heart sound or a pericardial vibration. The only apparent cause was a left ventricular false tendon extending from the septal endocardium to the left ventricular free wall, demonstrated by 2D echocardiography. This type of aberrant intracardiac band has already been described but the possibility of early diastolic stretching of this structure giving rise to an abnormal early diastolic sound does not seem to have been previously reported. PMID- 3105495 TI - [Hypertensive arteriopathy and atherogenesis: cellular and molecular interactions]. AB - The spontaneously hypertensive rat (SHR)--animal model for human essential hypertension--develops a generalized arteriopathy. The present paper discusses the atherogenic influence of hypertensive arterial lesions. The following changes in the intima might influence its permeability and barrier function, increase the trapping effect and stimulate the smooth muscle cell proliferation: the hyper reactivity of endothelial cells; the decreased thickness of endothelial cell periphery; the reduced intercellular junction pathways; the increase in basal lamina and glycosaminoglycan sub-endothelial material; the mononuclear cell infiltrations; the widened fenestrae in the internal elastic lamina. Some hypertensive changes of the tunica media may also interact with atherogenic process through reduced smooth muscle cell lipolytic capabilities, slowed transmural diffusion, perturbed efflux, aggravated media hypoxia, namely: the decrease in esterase and cholinesterase activities, the activations of some lysosomal enzymes, the increase in collagen, glycosaminoglycan and elastin content; the increased media thickness and transmural passage; the modified smooth muscle cell behavior. PMID- 3105496 TI - [The arterial wall and atherosclerosis]. PMID- 3105497 TI - [Aortic valve stenosis in patients over 50 years of age. Anatomy and trials at dilatation]. PMID- 3105498 TI - [Low molecular weight heparin in extracorporeal circulation. 1st clinical applications]. AB - The haemorrhagic complications inherent to the use of heparin during cardiac surgery led us, after a pilot experimental study, to try out a low molecular weight heparin (LMWH), PK 10169, which has weaker haemorrhagic effects in vitro. Our initial experience was confined to 23 patients with differing pathologies, undergoing cardiopulmonary bypass lasting 30 to 165 minutes. The modes of injection of YK 10169 varied according to the results, especially with respect to the limitation of peaks of anti-Xa activity; 8 patients were given one bolus intravenous injection, 9 were given a bolus injection and a continuous infusion, and 6 were only given the continuous infusion. Biological monitoring of anticoagulation was based on anti-Xa activity. Analysis of the biological results showed that the principal feature was the partial correction, and occasionally the non-correction of anti-Xa activity by protamine sulphate, with no correlation between this anti-Xa activity and postoperative bleeding. The authors report cases of severe postoperative bleeding despite the supposed theoretical and experimental weakly haemorrhagic properties of LMWH, and also discuss the inefficacy of protamine sulphate. The indications for LMWH for cardiopulmonary bypass which were retained, were the rare cases of heparin-induced thrombocytopaenia. In conclusion, it is possible to use LMWH during cardiac surgery but we do not advise using it routinely as its theoretical advantages are not confirmed in practice. PMID- 3105499 TI - [Medium term outcome of 191 cases of coronary insufficiency technically operable and treated medically]. AB - After evaluation by clinical examination, stress testing and coronary angiography, coronary patients may be classified into several subgroups according to the therapeutic orientation: 1) surgical and operable, 2) surgical but inoperable, 3) operable, but not immediately, 4) inoperable and not referred for operation. Groups 1 and 2 have severe ischaemia at rest or on exercise and an incomplete response to medical therapy: surgical revascularisation may be possible (Group 1) or not (Group 2). The surgical indication in Group 4 is not formal, but would be this so the operation would not be possible technically: this is the case for example in isolated thrombosis of the right coronary or left anterior descending arteries after infarction in their territories. This study concerns cases in Group 3; a total of 196 patients were deliberately treated medically after exercise stress testing had indicated a probable good prognosis despite patent coronary lesions (1.76 vessels with over 70% stenosis or thrombosis). Of the 1,181 patients who underwent exercise stress testing without therapy before coronary angiography between January 1979 and March 1983, 700 were operated (Group 1), 200 were inoperable (Group 2), 50 were inoperable and not referred for surgery (Group 4) and 196 were deliberate abstentions (Group 3); 35 patients underwent angioplasty; the average age of these 196 patients (168 men and 27 women) was 57.6 +/- 9 years (range 29 to 76 years). The incidence of single, double and triple vessel disease in this subgroup was 42%, 38% and 20%, respectively; 37% had previous infarction; 16% had atypical chest pain; 40% had stable angina, recent in 44% of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105500 TI - [Variations in the amplitude of the Q wave at V5 during computerized exercise test. Value in the diagnosis of coronary insufficiency]. AB - The aim of this study was to evaluate the diagnostic value of changes in Q wave amplitude in the V5 chest lead in coronary artery disease, especially for the detection of significant (greater than or equal to 75% narrowing) left interior descending disease. The stress tests of 227 patients were reviewed and confronted with the results of coronary angiography in 93 patients with angiographically normal arteries, and 134 patients with left anterior descending disease of the latter, 37 had single vessel disease, 38 had double vessel disease and 59, triple vessel disease. The average values of the Q wave amplitude in V5 at the peak of effort were 0.97 +/- 1.04 mm in the control group; 0.53 +/- 0.65 mm (p less than 0.01) in the group with single vessel disease; 0.46 +/- 0.66 mm (p less than 0.01) in the group with double vessel disease and 0.64 +/- 0.9 mm (p = 0.04) in the group with triple vessel disease. The mean variations of the amplitude of the Q wave in lead V5 on effort in the same group of patients were: +0.55 +/- 0.73 mm (p less than 0.001); + 0.11 +/- 0.66 mm (NS); + 0.02 +/- 0.5 mm (NS) and + 0.05 +/- 0.53 mm (NS), respectively. The Q wave in lead V5 was generally deeper on effort in the control group and the average variation in its amplitude was statistically significant only in this group. In the coronary patients, the Q wave in lead V5 was generally smaller and its amplitude did not change significantly on effort.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105501 TI - [Value of the computerized analysis of ST segment depression during exercise without myocardial infarction. Apropos of 807 cases]. AB - The diagnostic value of ST segment changes on exercise were reassessed by computerised analysis in 807 patients without myocardial infarction who underwent coronary angiography. All the stress tests were carried out according to Bruce's protocol with a system of continuous averaging of the ST segment in V5, V2 and VF. An abnormal response was defined by the association of the following three criteria: 1) ST depression less than or equal to 1 mm, 2) the algebraic sum of the depression + ST slope less than or equal to -1, 3) changes occurring during exercise or the first minute of recovery. A significant coronary lesion was defined as at least 50 per cent narrowing of the vessel lumen. In the study population the prevalence of lesions was 55 per cent in men and 18 per cent in women. The sensitivity of exercise stress testing was 69 per cent but the specificity was only 65 per cent. The positive predictive value was 70 per cent in men, 29 per cent in women; the negative predictive value was 90 per cent in women compared with 62 per cent in men. The predictive values depended on the interpretation of the amplitude, morphology and topography of the ST depression. The low sensitivity and specificity were independent of the coronary angiographic criteria and not related to the bias usually encountered in the correlation between stress testing and coronary angiography. These results show that the quantitative analysis of ST changes during computerised stress testing is not sufficiently accurate in itself to detect atherosclerotic coronary artery disease. PMID- 3105502 TI - [Percutaneous mitral valvuloplasty in the adult. Apropos of 5 cases]. AB - The results of percutaneous mitral valvuloplasty in 5 adult patients with mitral stenosis are presented. The average age was 55 years (37-72 years); 4 patients were in functional Class III and 1 in Class IV. The three oldest patients were in atrial fibrillation, and 2 of them had severe valvular and subvalvular lesions. Valvuloplasty was carried out with a "Trefoil" balloon (3 X 12 mm; effective cross sectional area at maximal inflation: 3.8 cm2). The procedure was successful in 4 patients. In the other patient, it was not possible to position the balloon across the stenotic valve. After valvuloplasty, the mean mitral gradient decreased (14 +/- 5 to 6 +/- 2 mmHg, p less than 0.05) without a significant change in cardiac index (2.9 +/- 0.5 vs 2.7 +/- 0.4 l/mn/m2; NS): this indicated an increased mitral valve surface area (1.1 +/- 0.2 to 1.8 +/- 0.05 cm2, p less than 0.05). In parallel, echocardiographic measurements of mitral valve surface area increased from 0.9 +/- 0.2 to 1.8 +/- 0.3 cm2, p less than 0.05, and Doppler pressure halt time fell from 220 +/- 50 to 116 +/- 13 ms, p less than 0.05. There were no operative complications and, in particular, no resulting angiographic mitral regurgitation. These preliminary results suggest that percutaneous mitral valvuloplasty may be a valuable alternative therapeutic procedure to surgery in selected patients. PMID- 3105503 TI - [Isolated stenosis of the left anterior descending coronary artery and regional function of the left ventricle]. AB - This study compared regional and global left ventricular function of a population of patients with a stenosis of the left anterior descending (LAD) artery and a control population in a prospective 18 months protocol. The 25 patients in the LAD group, 21 men and 4 women (55 +/- 9 years), had a pure and isolated stenosis of the LAD artery (70 +/- 8%) without infarction with normal global systolic function. The 12 patients in the control group strictly no cardiovascular disease after extensive investigation. Cardiac catheterisation was carried out in the conventional manner under the same conditions in both groups, after withdrawal of all medication. Regional wall motion was studied on 30 degrees right anterior oblique selective left ventriculography by a technique derived from Ingel's method using every frame of a cycle in terms of amplitude, velocity and time of segmental shortening and lengthening. The patients in the LAD group had normal cardiac function and no hypo or akinesia. The principal characteristic was the finding of anterior wall asynergy which was significantly different from the uneven contraction common in control subjects. This asynergy is observed from the end of systole to early diastole and features: early termination of anterior wall contraction (normalised contraction time: 86 +/- 13% vs 97 +/- 4% in the control group; p less than 0.02; and 90% in the inferior zone, NS, compared with the control group and p less than 0.05 compared with the anterior wall); dephased velocities of segmental shortening at the end of ejection (positive velocities in the inferior zones 0.17 +/- 1.7 circ/sec and negative velocities in the anterior zones, -0.34 +/- 2.2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105504 TI - [Protective effects of inhibitors of oxygen free radicals on the ischemic and reperfused heart. Applications to cardioplegia]. AB - Oxygen free radicals play an important role in the induction of myocardial lesions by the sequence ischaemic-reperfusion. The aim of this study was to determine whether the protection afforded by a cardioplegic solution could be improved by the addition of different anti-oxygen free radical agents. Forty isolated, perfused, rat hearts' isovolumic contraction systems were divided into 5 groups of 8. In 4 groups, cardioplegia was stopped for 90 minutes in normothermia and then reperfused for 45 minutes. These hearts received a single initial injection of either standard cardioplegic solution or a solution enriched with dismutase peroxide (200,000 U/l), reduced glutathione (0.1 mM) or peroxidase (6,000 U/l). The fifth group of hearts was continually aerobically reperfused and served as a non-ischaemic control group. Based on post-ischaemic values of the pressure developed (maximal systolic-diastolic pressure), LVdP/dt, diastolic pressure and coronary flow, the best myocardial protection was observed in those hearts given cardioplegic solution enriched with peroxidase, the haemodynamic indices being comparable to those of the non-ischaemic controls. These results confirm that myocardial protection with cardioplegic solutions can be improved by the addition of anti-oxygen free radical agents, especially peroxidase which inactivates both hydrogen peroxide (precursor of the very cytotoxic hydroxyl radical) and some hydroperoxides, so interrupting the self-sustaining chain of lipidoperoxidation and limiting the damaging effects of this reaction on the cardiac cell membranes. PMID- 3105505 TI - [Hypertrophic obstructive cardiomyopathy in elderly patients. Retrospective study of 23 cases]. AB - This retrospective study was based on data obtained from 23 patients over 65 years old (72 +/- 1.04 years) with hypertrophic obstructive cardiomyopathy followed up for 3 years (37.2 +/- 5.4 months) in whom the diagnosis was established essentially on phonomechanographic and echocardiographic criteria under basal conditions or during pharmacodynamic stress testing when the initial examination was inconclusive. Under these conditions, diagnostic catheterisation was only required in 9 cases. The incidence of this disease seems to be substantially underestimated in this age group; clinical symptoms and ECG or chest X-ray changes are often attributed to other pathologies if these patients are not thoroughly investigated. In our experience, patients over 65 years represent 20 per cent of the total population of hypertrophic obstructive cardiomyopathy admitted to our Department during the 6 years' study period. Accurate diagnosis is important because of the therapeutic implications; digitalis and vasodilator therapy especially with nitrate derivatives are poorly tolerated by these patients. Betablockers and verapamil seem to be beneficial, judged on the decrease in the number of symptomatic patients when given these drugs. Only one of the 3 deaths observed in the 20 patients followed-up was attributed to cardiac causes, which seems to confirm the lower mortality rate in older patients with this condition. PMID- 3105507 TI - [2 cases of coronary embolism. Angiographic diagnosis and anatomopathological confirmation]. AB - The authors report two cases selected from a series of 61 cases of coronary embolism observed over an 18 year period at the Cardiovascular Hospital (Lyon) out of 4,860 autopsies of adult patients who died of cardiovascular causes. These two cases underwent coronary angiography, the results of which correlated with the autopsy findings. The authors review the causes and clinical manifestations of coronary embolism and compare their results with previously reported data, to establish the radiological features of coronary embolism. They notice the regular appearance of obstruction due to embolism and underline the importance of the associated negative signs (normality of the rest of the coronary circulation, absence of collateral vessels...) which makes the angiographic diagnosis one of elimination. PMID- 3105506 TI - [Prevention of myocardial ischemia during exercise 8 hours after use of transdermal nitrate derivatives]. AB - A controlled (placebo) double blind trial of a 20 cm2 transdermal system delivering 10 mg of Trinitrin per 24 hours, was carried out in 18 patients with stable angina and significant coronary artery disease. The exercise stress tests were performed at the same time of day using Bruce's protocol and computerised analysis (Case Marquette) after a 48 hour wash out period. All patients had two basal positive and reproducible exercise tests interrupted because of induced anginal pain and/or greater than or equal to 3.5 mm ST depression. There was no significant difference between the basal exercise stress tests and those performed after placebo. With the active drug the onset of ischaemia was delayed (ST less than -1 mm = 217 +/- 122 sec vs 150 +/- 70 sec with placebo, p less than 0.01); the duration of exercise was prolonged (419 +/- 119 sec vs 328 +/- 94 sec with placebo, p less than 0.01); for the same theoretical maximal heart rate, the ST depression was less (-1.6 +/- 0.9 mm vs -2.1 +/- 0.7 mm with placebo, p less than 0.01). On the other hand, the double rate pressure product was unchanged at rest and on effort. These results obtained after a 48 hour therapeutic window show statistically significant benefits with an increase in exercise tolerance and a decrease in myocardial ischaemia 8 hours after the application of transdermal Trinitrin system. PMID- 3105509 TI - [Postpartum myocardial infarction with normal coronary arteries. Apropos of a case]. AB - A case of painless anteroseptal and high lateral wall infarction presenting as cardiogenic shock with pulmonary oedema 24 hours after childbirth complicated by severe post partum haemorrhage with a coagulation defect, is reported. Coronary angiography performed one month later was normal, with a negative ergometrine provocation test. The authors review five previous reports in the medical literature, and discuss the possible physiopathological mechanisms which, alone or in association could have operated in the reported case. PMID- 3105508 TI - [Acute myocarditis in Lyme's syndrome. Value of myocardial scintigraphy with gallium 67]. AB - The authors report the case of a 35 year old man with no known previous cardiac disease. One month after a tic bite causing diffuse abdominal erythema, he was admitted to hospital with fever, breathlessness and bradycardia. The electrocardiogramme showed first degree atrioventricular block with a sinoatrial block (SA = 200 ms, AH = 240 ms). Echocardiography eliminated the diagnosis of pericardial effusion. Thallium 201 myocardial scintigraphy was pathological and showed irregular global uptake suggesting cardiomyopathy. Gallium 67 scintigraphy showed increased uptake in the left ventricle. The evolution was uncomplicated with normalisation of clinical, ECG and radiological changes. Cardiac catheterisation and angiography eliminated ischaemic and primary cardiomyopathy. Control radionuclide investigations were normal at one month: there was no persistent abnormal Gallium uptake. The diagnosis of Lyme's syndrome was confirmed by positive serology with successive titres of 1/1024 and 1/2048 (significant at titres over 1/256). This unusual case illustrates: the risk of myocardial disease in Lyme's syndrome; the diagnostic value of Gallium 67 scintigraphy in acute myocarditis: Gallium seems to fix specifically on inflamed tissues, so distinguishing myocarditis from primary cardiomyopathies. PMID- 3105510 TI - [False subaortic aneurysm after surgery of calcified aortic stenosis. Apropos of a case treated successfully]. AB - The authors report a case of false aneurysm of the posterior subaortic region of the left ventricle after a technically difficult surgical decalcification in a case of aortic stenosis. At reoperation, the surgeon used the femoral artery and both vena cavae for canulation. A direct approach of this "vascular" tumour, which was exterior to the great vessels, confirmed the diagnosis and enabled the localisation of the internal orifice inside the left ventricle. This was closed simply by suturing. No previous cases of this kind were found in the literature. This report underlines the necessity of taking the greatest care when decalcifying this region in order to avoid this type of serious complication. PMID- 3105511 TI - [Congenital intercoronary arterial anastomosis. Apropos of a case and review of the literature]. AB - The authors report a case of coronary arterial anastomosis between the right coronary and left circumflex arteries in the absence of other coronary pathology. This is an exceptionally rare congenital malformation which is situated either in the atrioventricular groove or at the apex in the interventricular groove. It constitutes a diagnostic pitfall because, in contrast to a collateral circulation, it is not an indirect sign of occlusive coronary artery. PMID- 3105512 TI - [Supplementary parenteral nutrition in premature infants. Adaptation to amino acid intake]. AB - The authors report a controlled study of the use of 2 types of amino-acid solutions for premature infants nutrition in the first days of life, one of the solution (solution I) being adapted for prematures. The average amino-acid blood levels in prematures receiving solution I were close to those observed in cord blood; Plasma taurine, alanine and arginine concentrations were significantly lower with normalized levels of aromatic amino-acids, lysine, taurine and proline; serum ammonia level was also lower. This study shows that using an amino acid solution adapted to prematures as a supplement to parenteral nutrition during the first days of life allows to progressively increase the nitrogen intakes without inducing dangerous plasma levels of some amino-acids. PMID- 3105513 TI - Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. III. Morphometric assessment of the dynamic changes in post-capillary venules as regulatory elements of lymphocyte recirculation in tumor-draining lymph nodes. AB - To evaluate the dynamics of lymphocyte recirculation in tumor-bearing mice, the post-capillary venules (PCV) were subjected to quantitative measurements in the regional (RLN) and nonregional (NRLN) lymph nodes during the progression of P815X2 mastocytoma in syngeneic DBA/2 mice. Mice were sacrificed at two-day intervals, and RLNs and NRLNs were analysed for their content of B- and T lymphocytes and their subsets, demonstrated by immunoperoxidase technique using monoclonal antibodies; Anti-Thy 1.2 (T cells), Anti-Lyt 1 (T-helper cells), Anti Lyt 2 (T-suppressor cells), and Anti-I-Ad (B cell) antigens, separately in the B- and T-cell compartments. In the PCVs, migration index (MI) and endothelial height (Hend) were measured. There was a biphasic elevation of MI in the RLNs, as compared with only a late rise in the NRLNs, reaching the peak (1.54) on day 14. In RLNs, there was a sharp reduction in Hend starting from the values (6.37 microns) on day 2, down to 4.79 microns on day 8. This is followed by rapid elevation close to the second-day values, e.g. 6.07 on day 10. The changes in MI paralleled the early influx of B cells, as evidenced by the decrease of Thy 1.2+/I-Ad+ cell ratio and a late recruitment of T cells as indicated by the elevation of that ratio as well as the Hend values in both the RLNs and NRLNs. The present experiment shows that morphology of PCVs in the RLNs and in NRLNs of P815X2-bearing mice is subjected to alterations reflecting the dynamics of lymphocyte recruitment into these organs. When combined with lymphocyte subset enumeration using monoclonal antibodies, the quantitative analysis of the PCVs permits predictions to be made on the recirculatory activity of these cell populations during the tumor progression. PMID- 3105514 TI - Effects of locally applied enzyme inhibitors of the arachidonic acid cascade on follicle growth and intra-ovarian oocyte release in hyperstimulated rabbits. AB - This study was conducted to examine follicle growth and intra-ovarian oocyte release in rabbit ovaries influenced by a local application of prostaglandin formation inhibitors. While five rabbits remained as unstimulated controls, twenty-seven mature rabbits were hyperstimulated by pure follicle stimulating hormone (FSH) followed by human chorionic gonadotropin (hCG) at time 0. At the same time, 1 mg lonazolac (lonazolac group), indomethacin (indomethacin group) or saline (so-called gonadotrophic stimulated controls) was applied into the vagina of each group. Both ovaries of each animal were evaluated morphometrically at 15, 20, 28 and 48 hr after hCG. The absolute numbers of smaller-sized preantral follicles were always higher in the gonadotrophic stimulated controls than in the unstimulated controls, the lonazolac, or the indomethacin group. The numbers of larger-sized preantral and antral follicles showed no differences. Unlike the gonadotrophic stimulated controls and the lonazolac group, the indomethacin group displayed an increase in its mature structures (large-sized antral and preovulatory follicles, follicle and luteinized cysts) from 20 to 28 hr after hCG. Call-Exner bodies underwent pseudomucification in preovulatory follicles. The absolute numbers of Call-Exner bodies were augmented by indomethacin. Maturation division of oocytes began to decrease in all three treated groups between 15 and 20 hr post hCG, but the height of intra-ovarian oocyte release (IOR) appeared at 28 hr. This coincided with a striking thrombus formation. It is assumed that: 1) lonazolac and indomethacin inhibit early development of proliferating follicles; 2) lonazolac and indomethacin have no effects on the maturation division of the oocyte and of IOR; 3) IOR extends over a longer period after ovulation induction in contrast to the maturation division of the oocyte; and 4) thrombus formation is related to IOR. PMID- 3105515 TI - Periodic acid in the staining of acid-fast bacilli in tissue section. PMID- 3105516 TI - Unusual thoracic manifestations of epithelioid hemangioendothelioma. AB - Intravascular bronchioloalveolar tumors are now recognized as the pulmonary analogue of epithelioid hemangioendotheliomas of the somatic soft tissues. These low-grade endothelial sarcomas have a typical histologic appearance and usually present as bilateral pulmonary nodules in young women. The present report describes four unusual clinical manifestations of the epithelioid hemangioendothelioma: as an anterior mediastinal mass, as diffuse pleural thickening resembling malignant mesothelioma, as a metastatic carcinoma with cancerization of the lymphatics (lymphagitic carcinoma), and as a solitary peripheral calcified nodule. These anomalous clinical presentations correspond to unusual histologic appearances of the tumor at open-lung biopsy, and need to be recognized by both the clinician and the pathologist. PMID- 3105517 TI - Thoracic lymphangiomatosis. AB - We report the case of a 33-year-old man with thoracic lymphangiomatosis. The patient had experienced a 17-year history of recurrent chylothoraces and worsening cor pulmonale. The neoplasm was composed of histologically benign lymphatic channels lined by endothelial cells containing factor VIII-related antigen by immunohistochemical staining. The neoplasm filled the chest cavity, thereby compressing the lungs and involving the pleura, mediastinum, and thoracic vertebrae. We contrast this case with previous reports of lymphangiomatosis. PMID- 3105518 TI - Studies on histaminergic compounds, IV. Non-isosterism between the imidazole, guanidino and isothiourea moieties at the H2-receptor. PMID- 3105519 TI - Quality care and cost-effectiveness. An organized approach to problem solving. AB - The reflexive approach to rising hospital costs and decreased revenue is to balance the budget by curtailing expenses. This places budgetary limitations on personnel, supplies, and equipment and ultimately has an impact on the quality of care. An alternative approach is to modify traditional practice patterns so that quality is preserved and costs are reduced. We reviewed elective class I and II coronary artery bypass graft surgery on a cost basis to identify potential problems. High costs in blood and blood-product usage were identified. An in depth analysis of practice patterns was conducted, and comparisons were made between data from our hospital and other institutions. Modifications that improved quality and reduced costs were designed. Blood and blood-product usage was reduced from an average of 9.2 U to 3.4 U per case, resulting in an estimated cost avoidance of $111,286 per year. No cost advantage was observed with the use of cell savers, membrane oxygenators, or automated coagulation analysis in these routine short pump run surgeries. Though not cost-effective, the cell saver did allow the salvage of 2 U of blood per case. Mediastinal drainage systems (Sorenson) as well as reeducation regarding the safe, albeit low, hematocrit (no transfusions for hematocrits above 25% [0.25]) were effective in eliminating unnecessary use of potentially dangerous and expensive blood products. PMID- 3105520 TI - [Effect of bacterial toxins on microcirculation (experimental research)]. AB - Histological and biomicroscopic methods were used to study the effects of toxic lemic and meningococcal microbial fractions on mesenteric blood microcirculation in rats. Aggregation ability of red blood cells and thrombocytes was investigated. The sublethal dose of meningococcal toxins was shown to induce marked impairment in the blood microcirculation 30 minutes after intravenous administration. The lethal dose of lemic toxins manifests itself later (in 2-4 hours). Meningococcal toxins are characterized by the increase in the aggregation ability of erythrocytes and thrombocytes in initial observation periods; lemic toxins increase the thrombocyte aggregation and produce almost no effect on erythrocyte aggregation. PMID- 3105521 TI - [Experimental dilatation of the cecum and colon in rats. III. A model induced by prolonged administration of lactose in the diet of animals in the chronic phase of infection by the Y strain of T. cruzi]. AB - Female Wistar albino rats (30 days of age), weighing about 60 g, were inoculated intraperitoneally with 1000 parasites/g of the Y strain of T. cruzi. The strain of T. cruzi has been maintained by in vivo passage of the parasites from mice to mice in the Department of Parasitology, Microbiology and Immunology, Medical School of Ribeirao Preto. Rats of the same sex and age were used as controls. One hundred days after inoculation the animals were allocated into 4 groups: group I (control), divided into subgroup L (fed lactose for 4 weeks) and subgroup S (fed saccharose for 4 weeks); group II (inoculated), divided into subgroup L (fed lactose for 4 weeks) and subgroup S (fed saccharose for 4 weeks); group III (control), divided into subgroup L-S (fed lactose for 4 weeks and saccharose for the following 4 weeks) and subgroup S (fed saccharose for 8 weeks); and group IV (inoculated), divided into subgroup L-S (fed lactose for 4 weeks and saccharose for the following 4 weeks) and subgroup S (fed saccharose for 8 weeks). The disaccharide (lactose or saccharose) was added to a standard laboratory diet, 25 g/100 g of the final weight of the diet. At the end of the experimental periods the animals were sacrificed in ether anesthesia. The volume of the large intestine was measured, and the weight of cecum and colon were recorded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105522 TI - Cerebro-ocular dysplasia-muscular dystrophy syndrome. Report of two cases. AB - Cerebro-ocular dysplasia-muscular dystrophy (COD-MD) syndrome is a rare disorder encompassing a triad of brain, eye, and muscle abnormalities. The principal central nervous system features are cerebral and cerebellar agyria micropolygyria, cortical disorganization, glial-mesodermal proliferation within the leptomeninges, neuronal heterotopias, hypoplasia of nerve tracts, hydrocephalus, and, occasionally, encephalocele. Ocular abnormalities include microphthalmia, cataract, immature anterior chamber angle, retinal dysplasia with or without retinal detachment, persistent hyperplastic primary vitreous, optic nerve hypoplasia, and coloboma. Skeletal muscle findings include fiber splitting, variable fiber size, and endomysial fibrosis. Recent evidence has shown that COD MD syndrome may be identical to the Walker-Warburg (also known as Warburg) syndrome. Fukuyama congenital muscular dystrophy is similar to the COD-MD and Walker-Warburg syndromes, although the ocular manifestations are less severe. We report the histopathologic findings in two siblings with multiple features of COD MD syndrome. PMID- 3105523 TI - The Lennox Gastaut syndrome. PMID- 3105524 TI - [Pseudomonas aeruginosa infections in turkey poults and treatment trials with apramycin]. PMID- 3105525 TI - Characterization of meprin, a membrane-bound metalloendopeptidase from mouse kidney. AB - Meprin is an intrinsic protein of the brush border, a specialized plasma membrane, of the mouse kidney. It is a metalloendopeptidase that contains 1 mol of zinc and 3 mol of calcium per mol of the 85,000-Mr subunit. The enzyme is isolated, and active, as a tetramer. The behaviour of the enzyme on SDS/polyacrylamide gels in the presence and absence of beta-mercaptoethanol indicates that the subunits are of the same Mr (approx. 85,000) and held together by intersubunit S--S bridges. Eight S-carboxymethyl-L-cysteine residues were detected after reduction of the enzyme with beta-mercaptoethanol and carboxymethylation with iodoacetate. The enzyme is a glycoprotein and contains approx. 18% carbohydrate. Most of the carbohydrate is removed by endoglycosidase F, indicating that the sugar residues are N-linked. The isoelectric point of the enzyme is between pH 4 and 5, and the purified protein yields a pattern of evenly spaced bands in this range on isoelectric focusing. The peptide-bond specificity of the enzyme has been determined by using the oxidized B-chain of insulin as substrate. In all, 15 peptide degradation products were separated by h.p.l.c. and analysed for their amino acid content and N-terminal amino acid residue. The prevalent peptide-bond cleavages were between Gly20 and Glu21, Phe24 and Phe25 and between Phe25 and Tyr26. Other sites of cleavage were Leu6-Cysteic acid7, Ala14-Leu15, His10-Leu11, Leu17-Val18, Gly8-Ser9, Leu15-Tyr16, His5-Leu6. These results indicate that meprin has a preference for peptide bonds that are flanked by hydrophobic or neutral amino acid residues, but hydrolysis is not limited to these bonds. The ability of meprin to hydrolyse peptide bonds between small neutral and negatively charged amino acid residues distinguishes it from several other metalloendopeptidases. PMID- 3105527 TI - The occurrence of a lipoxygenase pathway in reticulocytes of various species. AB - Reticulocytes from various species (rat, mouse, rhesus monkey) obtained by phenylhydrazine treatment of the animals metabolized polyenoic fatty acids via a lipoxygenase pathway. Linoleic acid was converted to 13-hydro(pero)xy 9,11(Z,E)octadecadienoic acid [13-H(P)ODE] and 9-hydro(pero)xy 10,12(E,Z)octadecadienoic acid [9-H(P)ODE], whereas arachidonic acid was oxygenated to 15-hydroxy-5,8,11,13(Z,Z,Z,E)eicosatetraenoic acid (15-HETE) as shown by straight-phase high-pressure liquid chromatography (SP-HPLC). Addition of calcium and ionophore A 23,187 strongly enhanced the formation of lipoxygenase products, whereas 5,8,11,14eicosatetraenoic acid (ETYA) completely inhibited their formation. Estimates of the specific radioactivities of the lipoxygenase products indicate differences in the metabolization of externally added and endogenously released polyenoic fatty acids. These results strongly suggest that lipoxygenases generally occur in immature red blood cells. PMID- 3105526 TI - Decarboxylation of alpha-difluoromethylornithine by ornithine decarboxylase. AB - The mechanism of inactivation of rodent ornithine decarboxylase by alpha difluoromethylornithine (DFMO) was studied using the inhibitor labelled with 14C in both the 1 and the 5 positions. [1-14C]DFMO was a substrate and was decarboxylated by the enzyme yielding 14CO2. A radioactive metabolite derived from [5-14C]DFMO was bound to the enzyme, and the extent of binding paralleled the irreversible inactivation of ornithine decarboxylase. The partition ratio of decarboxylation to binding was approx. 3.3. These results provide support for the postulated mechanism of action of DFMO [Metcalf, Bey, Danzin, Jung, Casera & Vevert (1978) J. Am. Chem. Soc. 100, 2551-2553], in which enzymic decarboxylation of the inhibitor leads to the generation of a conjugated imine, which then alkylates a nucleophilic residue on the enzyme. PMID- 3105528 TI - Pure enzymes in a test hierarchy for antibronchoconstrictory lipoxygenase inhibitors. AB - A test hierarchy for potential antibronchoconstrictive drugs acting as lipoxygenase inhibitors was developed which includes a purified mammalian lipoxygenase/leukotriene A4 synthase, purified cyclooxygenase, arachidonic acid metabolism of polymorphonuclear leukocytes, arachidonic acid-induced contraction of lung strips, isolated human bronchi, and ovalbumin-induced bronchoconstriction with sensitized guinea pigs. The lipoxygenase from rabbit reticulocytes turned out to be superior to a variety of other animal and plant lipoxygenases. Among the various test systems with respiratory tract preparations, the arachidonic acid-induced contraction of guinea pig lung strips gave the most reliable results in the search for new antiasthmatic drugs. The validity of the test hierarchy was ascertained in screening investigations. Novel classes of antibronchoconstrictory lipoxygenase inhibitors were found. PMID- 3105529 TI - The initiation of glycogen synthesis. PMID- 3105530 TI - Virus, toxin, complement: common actions and their prevention by Ca2+ or Zn2+. PMID- 3105531 TI - L-threo-3,4-dihydroxyphenylserine (DOPS) aldolase: a new enzyme cleaving DOPS into protocatechualdehyde and glycine. AB - An enzyme which cleaves L-threo-3,4-dihydroxyphenylserine into protocatechualdehyde and glycine was demonstrated in extracts of human brains. Equimolar production of protocachualdehyde and glycine was quantitatively confirmed using high-performance liquid chromatography. In subcellular fractions of the brain, the highest enzyme activity was found in cytosol and soluble fraction. L-threo-DOPS proved to be the best substrate for this enzyme. The L erythroisomer was less active and D-threo- and D-erythro-isomers were essentially inactive. The enzyme activity has an optimal pH around 7.4, and requires pyridoxal phosphate for maximal activity. PMID- 3105532 TI - Heterogeneity of cholecystokinin receptors in pancreas. AB - Specific labeling of a major Mr 85-95 K protein was obtained using the SH, NH2 heterobifunctional cross-linker m-maleimidobenzoyl N-hydroxysuccinimide ester (MBS) to affinity label cholecystokinin (CCK) receptors on rat pancreatic plasma membranes, pancreatic acinar cells and acinar cell tumor membranes with 125I-CCK 33. Endoglycosidase F (endo F) digestion of this species in gel slices indicated that at least two components were present which contain N-linked glycans. The smaller protein of Mr approximately 85 K was digested by endo F to a final product of approximately Mr 62 K while the larger Mr approximately 95 K protein generated two endo F products of Mr 55 K and Mr 43 K. These findings suggest that the receptor for CCK on pancreatic acinar cells exhibits an oligomeric structure, possessing two distinct CCK-binding proteins. PMID- 3105533 TI - Activation of polyamine biosynthetic decarboxylases during the acute phase response of rat liver. AB - The activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase increase in the livers of rats during the acute-phase response to inflammation. The increase reaches its maximum at 2.5 hr from injection of turpentine, and is maintained at the same level for the following 2 days. Pretreatment in vivo with an inhibitor of cyclooxygenase prevents the inflammation-associated increases of both polyamine biosynthetic decarboxylases: an inhibitor of the lipoxygenase pathway seems to counteract only the increase of ornithine decarboxylase. The administration of diaminopropane, an inhibitor of ornithine decarboxylase, has only limited effects on the activation of RNA synthesis by liver nuclei, which occurs 10 hr after turpentine treatment. The results suggest that stimulation of the polyamine biosynthetic decarboxylases is surely part of the acute-phase response and depends on the previous activation of arachidonate metabolism: however its role in supporting later events of the acute-phase response will need further investigations. PMID- 3105534 TI - GTP-binding protein(s) in green plant, Lemna paucicostata. AB - GTP-binding protein(s) assayed by [35S]GTP gamma S was detected in the extract of Lemna paucicostata containing membrane components. About 15% of [35S]GTP gamma S activated GTP-binding protein, separated from unbound [35S]GTP gamma S by gel filtration, was retained on Millipore HAWP membrane filter. 80% of [35S]GTP gamma S activated protein, mixed with charcoal solution, remained in the supernatant after centrifugation of the mixture. Successive treatments of the assay mixture by charcoal solution established the assay system for the activation of GTP binding protein. The Km value for the activation of GTP-binding protein was 8 nM. PMID- 3105535 TI - On the formation of a dicloxacillin-p-hydroxymercuribenzoate suicide complex mediated by beta-lactamase I from Bacillus cereus. AB - p-Hydroxymercuribenzoate is a non-competitive inhibitor of beta-lactamase I from Bacillus cereus and also, after preliminary preincubation, an inactivator of the enzyme. Submitted to the simultaneous action of PCMB plus dicloxacillin, the enzyme completely loses its activity. Extensive dialysis can restore the enzymatic activity only if preincubation had been carried out with either PCMB or dicloxacillin but not if both inhibitors had been simultaneously present. Mercaptoethanol protects the enzyme from the action of PCMB, but not from the severe inactivation caused by dicloxacillin-PCMB mixtures. All these data suggest the formation of a complex between PCMB and the acyl-enzyme intermediate generated upon hydrolysis of the beta-lactam bond of dicloxacillin. PMID- 3105536 TI - Studies of peptide conformation in the design of peptide agonists. PMID- 3105537 TI - Subcellular localization and properties of cytochrome P-450 and UDP glucuronosyltransferase in the rainbow trout kidney. AB - Rainbow trout kidney was subfractionated by differential centrifugation to obtain preparations suitable for the study of xenobiotic metabolizing enzymes and to ascertain the distribution of these activities in the cell. The cytochrome P-450 dependent monooxygenase, NADPH-cytochrome c reductase, and UDP glucuronosyltransferase, which are enzymes important in the biotransformation of xenobiotics, were enriched in the microsomal fraction. Another xenobiotic metabolizing enzyme, epoxide hydrolase, was enriched in the mitochondrial and microsomal fractions almost to the same extent. Cytochrome P-450-dependent monooxygenase and UDP glucuronosyltransferase activities were characterized in the trout kidney microsomes. The cytochrome P-450 deethylation of 7 ethoxycoumarin and 7-ethoxyresorufin as well as the glucuronidation of p nitrophenol in the kidney were found to proceed at rates comparable to those occurring in the liver. The difference spectrum of the complex between carbon monoxide and reduced trout kidney microsomes showed a peak at 448.5 nm. Addition of 7-ethoxycoumarin to kidney microsomes produced an absorbance change in difference spectrum similar to the substrate binding spectrum found in rainbow trout liver and rat liver microsomes. PMID- 3105538 TI - Preparative HPLC purification of prostaglandin endoperoxides and isolation of novel cyclooxygenase-derived arachidonic acid metabolites. AB - A preparative HPLC purification scheme for the isolation of prostaglandin endoperoxides prepared by short-time incubation of [1-14C]-labelled arachidonic acid (AA) with sheep seminal vesicle microsomes was developed. Milligram quantities of prostaglandin G2 (PGG2) and prostaglandin H2 (PGH2) were obtained in greater than or equal to 95% purity within shortest time. Furthermore, careful application of this HPLC technique led to the isolation of two minor [1-14C] labelled fractions which according to their spectral and chromatographic characteristics, were identical with 15(S)-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) and 15(S)-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE). Another HETE substituted at either C11 or C12 was also present. The formation of these products was mediated by cyclooxygenase as evidenced by aspirin (100 microM) and indomethacin (10 microM) inhibition. Sulfhydryl-blocking agents such as p-hydroxymercuribenzoate (1 mM) and/or the 12-lipoxygenase inhibitor esculetin (100 microM) were without effect. In addition to these AA metabolites four other fractions contained arachidonate-derived endoperoxides with antiaggregatory properties, all of which released malondialdehyde upon incubation with thromboxane A2 synthase. No thromboxane formation was observed although turnover numbers were comparable to those of PGG2 and PGH2. The formation of these endoperoxides did not occur via enzymatic or non-enzymatic degradation of PGG2 or PGH2. The exact chemical nature of these endoperoxides remains to be established. PMID- 3105539 TI - Nitroimidazole bioreductive metabolism. Quantitation and characterisation of mouse tissue benznidazole nitroreductases in vivo and in vitro. AB - We have investigated the nitroreduction of the 2-nitroimidazole benznidazole (BENZO) to its corresponding amine by murine normal tissues and tumours. In vivo concentrations of BENZO and its amine metabolite were measured by HPLC 3 hr after BENZO, 2.5 mmoles kg-1 i.p. This gave plasma and tissue BENZO concentrations of 96-160 micrograms ml-1 or g-1. Mouse plasma, KHT and RIF-1 tumour BENZO amine concentrations were very low (0.3-1.4 micrograms g-1); kidney and EMT6 tumours had intermediate levels; and liver contained very high amine levels (approximately 50 micrograms g-1). Three per cent of the BENZO dose was recovered as amine in the 24 hr urine, compared to 5% for the parent compound. Nitroreduction to the amine was demonstrated with liver and tumour preparations under N2 in vitro. The reaction was highly dependent on NADPH, and inhibited extensively in air. With liver microsomes and whole homogenates 2 and 3 moles respectively of BENZO were consumed per mole of amine formed. Inhibitor studies showed that NADPH: cytochrome P-450 (cytochrome c) reductase and cytochrome P-450 were both involved in BENZO reduction, predominantly at early and late reduction steps respectively. Aldehyde oxidase contributed to the cytosolic nitroreduction. Purified buttermilk xanthine oxidase also reduced BENZO to its amine under anaerobic conditions in vitro, but very inefficiently. The apparent Km and Vmax for BENZO amine production by whole liver homogenates were 0.148 mM and 1.45 nmole min-1 mg-1 protein respectively. Tumour homogenates were less active than liver; e.g. Vmax for the KHT tumour was 6-10-fold lower. PMID- 3105540 TI - Changes in rat hepatic microsomal mixed function oxidase activity following exposure to halothane under various oxygen concentrations. AB - This study demonstrates that the exposure of phenobarbitone-treated rats to halothane at an oxygen concentration of either 10% or 14% results in marked decreases in cytochrome P-450 content and aminopyrine demethylase activity in animals sacrificed from 1 to 48 hr post-exposure. The alterations observed in the hepatic mixed function oxidase system were accompanied by increases in serum alanine aminotransferase (ALT), ornithine carbamyl transferase (OCT) and changes in liver pathology. However, the minor changes in cytochrome P-450 content and aminopyrine demethylase activity observed following exposure of enzyme-induced rats to halothane under normoxic conditions (i.e. 21% oxygen) were not of a sufficient magnitude to lead to hepatic cell necrosis. Halothane administration in the absence of phenobarbitone pretreatment (i.e. 21% oxygen) or during hypoxia alone (i.e. either 10% or 14% oxygen) did not result in any systematic changes in the parameters assayed. The results suggest that cytochrome P-450 may catalyse its own inactivation by virtue of greater free radical production under conditions which favour the non-oxygen dependent metabolism of halothane. The impairment in microsomal function as evidenced by decreases in cytochrome P-450 and aminopyrine demethylase activity are considered to occur as a primary consequence of the reductive metabolism of halothane. Data are presented which support the concept of the initiation of hepatic damage occurring during the period of anaesthesia with halothane. PMID- 3105542 TI - Effect of a single subtoxic dose of aflatoxin B1 (AFB1) on glucose-6-phosphate dehydrogenase in mouse liver. PMID- 3105541 TI - The drug methoxsalen, a suicide substrate for cytochrome P-450, decreases the metabolic activation, and prevents the hepatotoxicity, of carbon tetrachloride in mice. AB - Methoxsalen, a potent suicide inhibitor of cytochrome P-450 that can be used in humans, might be of value for the prevention of hepatitis in subjects with carbon tetrachloride poisoning. As a preliminary step, we have determined its effects on the hepatotoxicity of carbon tetrachloride in mice. Several monooxygenase activities, the in vitro covalent binding of carbon tetrachloride metabolites to microsomal proteins, and in vitro microsomal lipid peroxidation initiated by carbon tetrachloride metabolites were decreased by 60-90% in microsomes from mice killed 2 hr after the administration of methoxsalen (250 mumol X kg-1); microsomal lipid peroxidation mediated by endogenous iron and NADPH was not modified. Administration of methoxsalen (250 mumol X kg-1) 30 min before carbon tetrachloride (0.1 ml X kg-1) decreased both the in vivo formation of conjugated dienes in microsomal lipids and the in vivo covalent binding of carbon tetrachloride metabolites to lipids and proteins. This pretreatment completely prevented the hepatotoxicity of carbon tetrachloride. Other cytochrome P-450 inhibitors (cimetidine, SKF 525-A or piperonyl butoxide) given at this low molar dose (250 mumol X kg-1) exerted no protective effect. Methoxsalen (500 mumol X kg 1) was also effective, but only partially, when given 30 min after carbon tetrachloride (0.025 ml X kg-1). We conclude that pretreatment with methoxsalen decreases the metabolic activation of carbon tetrachloride, and completely prevents its hepatotoxicity in mice. Post-treatment with methoxsalen must be given early and is only partially effective in mice. PMID- 3105543 TI - The glucuronosyltransferases: what progress can pharmacologists expect from molecular biology and cellular enzymology? PMID- 3105544 TI - [Comparative hemodynamics action of glycero-2-nitrate and glycerol trinitrate in various species and the pharmacokinetics of glycerol-2-nitrate in the dog]. AB - Comparative Hemodynamic Activity of Glyceryl 2-Nitrate and Glyceryl Trinitrate in Various Species and Pharmacokinetics of Glyceryl 2-Nitrate in Dog A single dose of glyceryl 2-nitrate (G-2-N) had practically identical hypotensive and cardiovascular activity when administered intravenously or enterally to the anaesthetized rabbit, cat or dog. In all three species the hypotensive and also cardiovascular activity of G-2-N lasted much longer than that of glyceryl trinitrate (GTN, Nitro Mack). In the rabbit, cat and dog enterally active doses of GTN were 500-1000 times greater than parenterally active doses. In all species enterally administered GTN was about 8 times more active than enterally administered G-2-N. G-2-N is 100% bioavailable in the conscious dog. PMID- 3105545 TI - Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro 10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 2nd communication: inhibitory effects on acute inflammation and prostaglandin-related reactions. AB - Since a newly synthesized nonsteroidal antiinflammatory drug (NSAID) having weaker effects on gastrointestinal tract, 2-(10,11-dihydro-10 oxodibenzo[b,f]thiepin-2-yl)propionic acid (CN-100), was found to markedly inhibit rat paw edema induced by carrageenin and other phlogists, the effects of the drug on other acute inflammatory reactions and prostaglandins (PGs)-related reactions were compared with those of known NSAID in this study. At even a large dose of CN-100, 20 mg/kg, the drug did not significantly inhibit the increased vascular permeability induced by histamine in rat skin, but CN-100 could dose dependently inhibit the increased vascular permeability induced by acetic acid in mouse peritoneum. The inhibitory activity of CN-100 in the latter was equivalent to that of pranoprofen and indometacin. CN-100 exerted a potent inhibitory action on erythema induced by UV irradiation, which was equal to and 3 times stronger than pranoprofen and indometacin in activity, respectively. Since PGs participate in these acute inflammatory reactions, the effects of CN-100 on reactions relevant to PGs were examined. The drug at dose levels lower than antiinflammatory doses could prevent acute death and diarrhea induced by i.v. injection of arachidonic acid in rabbits and endotoxin in mice, respectively, suggesting that the drug had a potent inhibitory action on biosynthesis of PGs. The adverse effects of CN-100 on gastric and small intestinal mucosa was very weak, the activity being about one-tenth of that of pranoprofen and indometacin. PMID- 3105546 TI - Interaction between naloxone, chlordiazepoxide and valproic acid evaluated by emotional operant behaviour in the rat. AB - The effects of chlordiazepoxide (CDP, 5 mg/kg i.p.), the sodium salt of valproic acid (VPA, 200 mg/kg i.p.) and naloxone (Nx, 1 mg/kg s.c.) alone and CDP-Nx, VPA Nx association on schedule controlled behaviour with signalled unpunished and punished periods, were investigated. Our results show that CDP and VPA under both the unemotional (variable ratio reinforcement schedule 20%) and the emotional (continuous reinforced schedule associated with electric shock) components significantly increase responding in the Skinner box. Nx, on the multiple schedule, non-significantly reduces responding under both components. With CDP-Nx association the increase in responding under the unemotional component is less than in the case of the benzodiazepine alone, while under the emotional component the increase in responding is not appreciably affected. With the VPA-Nx association the responding rate is lower than that of the control under the unemotional component while under the emotional component the increase in responding is reduced compared to the VPA alone. The higher rates of unemotional and emotional responding with both CDP and VPA depend on the dipsogenic and disinhibiting effects by both drugs. The different rate of emotional and unemotional responding with CDP-Nx and VPA-Nx associations indicates a specific influence on GABAergic and other systems by CDP and VPA. PMID- 3105547 TI - Perspectives of radiotherapy. AB - The 5 years' survival rate of all cancer patients is 35-45%. In that survival rate radiotherapy takes part in 15%. By further development of radiological methods and techniques radiotherapy gains significance in the recent time. Optimizing radiation planning and tactics, all modern imaging techniques are applied consequently. The radiotherapist must be able to asses their immanent specifity which should remain object of the radiological training, even if separated into therapy and diagnostics. Dose distribution is calculated by computer; three-dimensional planning is done in tumors of the mediastinum, oesophagus carcinoma and paraaortic lymphomas. Critical description of radiation techniques, results, problems and prognoses are given by results in tumors of the epipharynx and gastric cancer. After-loading, done until now only in gynaecological tumors, is performed in recurrences of pharyngeal tumors by individually shaped applicators. Reducing the number of therapy failures as well as possible, the application of higher tumor doses, new kinds of rays as neutrons and combinations with physical and chemical methods is outlined. Modifications of radiation volumes are discussed, especially the irradiation of the complete abdomen in ovarian cancer, the irradiation of the complete body surface by electrons in mycosis fungoides, and the total body irradiation prior to autologue bone marrow transplantation. Modifications of fractionation are shown in short time radiation of bone metastases and single-time radiation of brain lesions. Low penetrating electron therapy facilitates intraoperative single-time irradiation. Because of higher biological efficiency neutrons and heavy ions allow to irradiate low sensible tumors or recurrences embedded in fibrotic tissue respectively. The combination with hyperthermia yields good results in tumors of the head and neck with better local response and total remissions of 59%. There are potentials in synchronising with chemotherapeutics. Remissions of different duration were achieved in 190 patients. Because of neutrotoxicity there are still problems in applicating radiosensitizers. New methods are applied treating endocrine active tumors by labelled hormone precursers. PMID- 3105548 TI - Hydrops fetalis associated with immunologic and nonimmunologic factors. AB - Described is a pregnancy complicated by severe Rh sensitization and hydrops fetalis which was managed aggressively with frequent intrauterine transfusions initiated at 21 1/2 weeks of gestation. No improvement or only temporary improvement of the fetal hydrops was observed after each intrauterine transfusion. Postmortem examination of the infant revealed the additional presence of nonimmunologic factors involved such as pulmonic atresia and lung hypoplasia. In cases of severe Rh sensitization associated with persistent fetal hydrops despite frequent intrauterine transfusions, the presence of coexistent factors for nonimmunologic fetal hydrops should be considered. PMID- 3105549 TI - Lipids in plasma of enterally-fed very low-birthweight neonates. AB - Plasma lipid patterns (total lipids, free glycerol, triglycerides, free fatty acids, and cholesterol) were studied in 10 very low-birthweight neonates assigned alternately to continuous drip versus every 2-hr bolus feedings with a formula containing 50% of its fat as medium-chain triglycerides. In the group of neonates fed continuously, plasma lipids did not vary significantly during the 4-day study. In the bolus-fed group, free fatty acid concentrations peaked 30 min after feeding; the other fractions did not vary significantly during 2 hr after feeding. Mean plasma concentrations of total lipids and triglycerides were higher in the continuous than in the bolus-fed neonates; concentrations of the other fractions were similar. Compared to plasma concentrations measured in a group of 4-day-old very low-birthweight neonates before any exposure to exogenous fat, continuously fed neonates had higher total lipid, triglyceride, free fatty acid, and cholesterol concentrations; bolus-fed neonates only had significantly higher triglyceride levels. These data emphasize the need to obtain information on plasma lipid patterns that is specific for gestational maturity, postnatal age, and method and type of feeding. PMID- 3105550 TI - Injury as externality: an economic perspective of trauma. AB - Economists emphasize the costs in dollars or other desirable outcomes of additional safety in contrast to safety experts who remind people to design safe products and operate them safely. Society loses emotionally and financially from traumatic injury. The emotional loss must be balanced against allowing individuals free choice and encouraging them to develop judgment. Individuals are viewed as making their own best safety decisions, although they must have good information and face the correct indentives. Currently, society subsidizes risk taking in many ways, thereby discouraging safety. Health and life insurance ought to be required along with liability insurance, to correct the incentives to drivers. In addition, regulation is required to deal with physical externalities. PMID- 3105551 TI - Injury as metaphor: towards an integration of perspectives. AB - Despite some notable successes, the prevailing injury rates connected with transportation, recreation and the workplace suggest that most of the findings from injury research have yet to be taken seriously by the American public or their political representatives. While a number of explanations might be offered for this situation, this paper carefully examines one which ties the social neglect of research knowledge to the diversity of premises and perspectives on injury. The lack of public action to prevent injury in many areas stems not so much from ignorance as from disagreement, and consequently, confusion over the nature of the injury problem and what should be done about it. Most of these disagreements can be traced to the contending perspectives on injury found in research. This paper examines three perspectives, those of economics, law and public health, and analyzes the metaphor each uses to characterize injury for clues about the sources of disagreement among them. Attention then turns to the rationale for integrating these perspective in ways that might accommodate the disagreements and serve as a basis for building a social consensus for public action. PMID- 3105552 TI - Public policy and automobile occupant restraint: an economist's perspective. AB - Cost-benefit analyses (CBAs) of policies intended to increase occupant restraint in automobiles typically find that such policies generate social benefits that exceed social costs, often by a considerable margin. The analyses are incomplete, however, due to their inability to incorporate potentially important costs and benefits that are hard to measure and monetize. Furthermore, analyses fail to account for distributional and political considerations. Despite these limitations, the evidence produced by the occupant restraint CBAs tends to bolster the case of advocates of mandatory passive restraints and other restraint policies. Support for governmental involvement can also be found in economic theory, although the theoretical case is not necessarily compelling. The principal lesson of this review of economic analysis of the occupant restraint issue is that analysis can inform an injury policy debate, but it cannot provide conclusive answers, nor can it serve as a substitute for the political decision making process. PMID- 3105553 TI - Evaluating voluntary risks of injury. AB - Making sound safety decisions requires accurate estimates of the costs of injuries and the benefits of their reduction. These estimates may be produced intuitively by citizens exposed to risk of injury, or formally, for analysts considering alternative safety policies. All such estimates rely on behavioral assumptions, regarding how people perceive and respond to to risks. They also rely on ethical assumptions, regarding how people should respond. The nature and validity of these assumptions are analyzed here, in order to provide a consumer's guide to techniques designed to evaluate risks and devise safety policies. PMID- 3105555 TI - [Cost analysis in the dental office]. PMID- 3105554 TI - [Serum hyperosmolality in long-term use of etomidate (Radenarcon)]. PMID- 3105556 TI - Heterologous immunoprecipitates also have potential for therapeutic use. AB - Potential therapeutic usefulness of administered enzymes is limited by toxicity and allergenicity. To overcome these problems we are using scurvy to test various enzyme modifications that may be suitable for therapy. L-Gulonolactone oxidase, which catalyzes the final step in ascorbic acid biosynthesis, is immunoprecipitated with specific antisera from rabbits and then cross-linked with glutaraldehyde. The modified enzyme retains activity sufficient to elicit ascorbic acid synthesis in scorbutic guinea pigs. Intraperitoneal injection of this altered enzyme to animals supplemented with L-gulonolactone increases plasma concentrations of the vitamin. Importantly, multiple doses of the complex are tolerated. Therefore, it is possible to prolong survival time of animals fed an ascorbic acid-deficient diet by this enzyme replacement therapy. This procedure can also be applied to other enzymes that have potential therapeutic use. Serum cholinesterase and asparaginase both retain activity after this modification and are tolerated in single or in weekly repeated injections. Following three or four weekly injections, an anaphylactic reaction to serum but not to enzyme can be elicited if they are injected intravascularly. We conclude that the stability of the immobilized foreign enzyme is a critical factor in lessening the toxicity to multiple injections of these foreign proteins. PMID- 3105557 TI - Endoscopic laser surgery. An alternative in laryngeal cancer treatment. AB - Thirty-three patients with newly diagnosed laryngeal carcinoma underwent endoscopic treatment with the carbon dioxide laser under microscopic control and venturi jet ventilation. Ten of these patients underwent emergency tumor debulking to relieve airway obstruction and to avoid emergency tracheotomy for airway control, and 23 had definitive treatment of superficial or frankly invasive carcinoma. Among the first group, all had an adequate airway after tumor debulking and could be treated with elective laryngectomy with or without radical neck dissection once their metabolic conditions had improved and they had been appropriately evaluated. Among the second group, two died of lung carcinoma but were free of laryngeal disease and two were lost to follow-up at one year. With a minimal three-year follow-up, six of the remaining 19 patients underwent additional laser procedures. None have required external laryngeal surgery or radiation therapy. Endoscopic laser therapy appears preferable to a more radical approach for carcinoma in situ, microinvasive carcinoma, or superficially invasive carcinoma of the larynx. PMID- 3105558 TI - Astemizole. Its use in the treatment of patients with chronic vertigo. AB - Thirty-eight patients with chronic vertigo and positional and/or spontaneous nystagmus finished a double-blind study to determine the efficacy of astemizole on nystagmus and its symptoms. Patients with Meniere's disease were excluded. The study took 13 weeks with a follow-up examination. Six to eight noncaloric electronystagmograms were recorded at determined intervals. Three doses of the drug, 5, 10, and 20 mg/d, and placebo were tested. A patient was considered a responder if the number of nystagmic beats occurring in eight head and body positions was reduced by 50% or more and the symptoms of vertigo were greatly reduced. Twenty-eight of the 38 patients were responders. Blood levels of astemizole were related to effectiveness. Patients did not respond to placebo. The onset of drug effect was slow. Astemizole appears to be useful and safe to try on the patient with chronic dizziness. PMID- 3105559 TI - Carbon dioxide laser in removal of polytef paste. AB - Teflon injection is the most popular surgical technique for improvement of voice in patients with a unilaterally paralyzed larynx. The results with this method usually are good, but cases of overinjection with resultant poor voice, airway compromise, or both, do occur. The carbon dioxide laser has become a standard instrument for laryngeal surgery, and it might reasonably be used in attempts to correct the overinjected vocal cord. Realizing that Teflon could share flammable characteristics with other polymers, such as rubber and polyvinylchloride, we investigated the effect of the carbon dioxide laser on fresh polytef paste (Mentor O & O Inc, Hingham, Mass) before using it in a patient with an overinjected hemilarynx. Fresh paste was found to ignite after exposure to standard laser power at normal time settings, both in room air and in an oxygen enriched atmosphere. To determine the effect of the laser on Teflon in situ, the paste was injected subcutaneously and intramuscularly into a rat. After a suitable interval of time, the Teflon was found to glow but not ignite when exposed to the laser under standard operating conditions. Only under high power in an oxygen-enriched environment did ignition occur. In our patient, the laser was used to incise the mucosa over the polytef granuloma, and standard microsurgical (nonlaser) techniques were used to complete the removal with good results. Laryngologists should be aware of the dangers of using the carbon dioxide laser on or near Teflon, especially in freshly injected vocal cords. PMID- 3105560 TI - Effects of oxytetracycline treatment on enzymes of hepatic glycogen metabolism in genetically diabetic (db/db) mice. AB - The effects of daily oxytetracycline treatment on the activities of hepatic glycogen synthase, glycogen phosphorylase, plasma glucose, and insulin, and on liver glycogen, free fatty acid, and triglyceride levels were examined in 8- to 15-week-old genetically diabetic and lean mice. Oxytetracycline administration resulted in substantial reductions in the plasma glucose and immunoreactive insulin levels in both diabetic and lean mice. The drug had no significant effect on the liver glycogen content in either phenotype, regardless of age, but it increased hepatic lipids and depressed body weights in lean animals. The most prominent effect of the drug was in markedly altering the activities of both glycogen synthase and phosphorylase in the liver of older diabetic mice. Oxytetracycline treatment produced a three-fold increase in the percentage of glycogen synthase I activity and reduced by one-third the percentage of glycogen phosphorylase a activity in 15-week-old diabetic mice. In age-matched lean mice treated with oxytetracycline, the percentage of glycogen synthase I activity increased significantly, but the percentage of phosphorylase a activity was unchanged. These data suggest that the drug may alter an aspect of hepatic glycogen metabolism which might lead to an inhibition of glycogenolysis and subsequent diminution of blood sugar levels in the diabetic. The present results show that, while oxytetracycline may be effective in reducing the severity of some of the diabetic symptoms associated with carbohydrate metabolism in this animal model of maturity-onset diabetes, the drug may have adverse effects on aspects of protein and lipid metabolism in these animals. PMID- 3105561 TI - Liver glycogen metabolism in endotoxin shock. I. Endotoxin administration decreases glycogen synthase activities in dog livers. AB - The effects of E. coli endotoxin administration on hepatic glycogen content and glycogen synthase activities in dogs were studied. Liver glycogen content was decreased by 80% 2 hr after endotoxin injection. When enzyme preparations were preincubated at 25 degrees C for 3 hr prior to their assays, 75% of total glycogen synthase was in I form in control dogs. Under such conditions, endotoxin administration decreased the percentage I activity from 75 to 37%; decreased the Vmax and Km for UDP-glucose for total glycogen synthase by 62.2 and 35.3%, respectively; decreased the Vmax and Km for UDP-glucose for glycogen synthase I by 75.6 and 15.6%, respectively; increased the A0.5 for glucose-6-P for the activation of glycogen synthase D by 126% at high (10 mM) and by 18-fold at low (1 mM) UDP-glucose concentration; increased the percentage D activity from 24 to 72%; decreased the I50 for ATP for the inhibition of total glycogen synthase by 49.7%; decreased the I50 for ATP for the inhibition of glycogen synthase I by 26.4%; and decreased the percentage I activity from 78 to 33% at ATP concentrations below 6 mM. When enzyme preparations were not preincubated prior to their assays, 90% of total glycogen synthase was in D form in control dogs. Under such conditions, endotoxin administration decreased the Vmax and Km for UDP glucose for total glycogen synthase by 47.1 and 33.3%, respectively, and increased the A0.5 for glucose-6-P for the activation of glycogen synthase D by 24.2% at high (10 mM) and by 106% at low (1 mM) UDP-glucose concentration. From these results, it is clear that endotoxin administration greatly impaired hepatic glycogenesis by decreasing the activity of glycogen synthase; this impairment is at least in part responsible for the depletion of liver glycogen content in endotoxin shock. Kinetic analyses revealed that the decrease in the activity of glycogen synthase in endotoxic shock is a result of a decrease in the interconversion of this enzyme from inactive to active form and an increase in the interconversion from active to inactive form. PMID- 3105563 TI - A case of heterozygous Fabry's disease with a short PR interval and giant negative T waves. AB - A 55 year old woman with heterozygous Fabry's disease presented with cardiac symptoms. The electrocardiogram showed a PR interval of 0.12 s and giant negative T waves, suggesting apical hypertrophic cardiomyopathy. Endomyocardial biopsy, however, revealed myelin like substances characteristic of Fabry's disease. Increasing thickness of the left ventricular wall was seen by echocardiography over a period of five years. A deficiency of alpha galactosidase activity in the leucocytes confirmed the diagnosis of Fabry's disease, although this patient had neither angiokeratoma or proteinuria. The possibility of Fabry's disease should be considered in patients with cardiomegaly of unknown cause and the following electrocardiographic abnormalities: a PR interval less than or equal to 0.12 s, high voltage QRS complexes in the left precordial leads, and giant negative T waves. PMID- 3105562 TI - Studies on the effect of inflammation on the acute phase response using rat liver slices. AB - Liver slices from control and inflamed rats were incubated in McCoy's medium and incorporation of [3H]leucine into liver and medium proteins and into albumin and alpha 1-acid glycoprotein was monitored over 48 hr. The release of the new acute phase reactant, sialyltransferase was also monitored in this system. Earlier observations in which liver slices were incubated for 6 hr showed that increased leucine incorporation into liver and medium proteins and alpha 1-acid glycoprotein, coupled with decreased incorporation into albumin, correlated with the acute phase response of these proteins. Increased incorporation of leucine into these proteins was found following 48 hr incubation in McCoy's medium showing that slices were able to express the changes characteristic of the acute phase response over this longer time period of incubation. Sialyltransferase was released into medium in a linear fashion up to 15 hr and continued to increase for 30 hr in this system; there was a substantial increase in release of enzyme activity from slices from inflamed rats when compared to controls. Monokine conditioned medium prepared from peritoneal exudate cells isolated from rats at various times after lipopolysaccharide administration was used to induce the acute phase response by intraperitoneal injection. Slices were prepared from these rats and sialyltransferase release from slices was monitored. Monokines prepared from peritoneal exudate cells isolated from rats at about 30 hr were most effective in stimulating sialyltransferase release from liver slices. PMID- 3105564 TI - Effects of halothane, isoflurane and enflurane on ventilation in children. AB - The ventilatory effects of halothane in eight children were compared with those of isoflurane in eight children and enflurane in six children. All studies were completed before surgery commenced, and the children received no preoperative medication. The depression of ventilation produced by the three agents increased in a dose-related fashion as the alveolar concentrations were increased, and the depression of ventilation that they produced in oxygen was greater than that produced by equipotent concentrations in nitrous oxide. While the increase in ventilatory frequency and the decrease in TE associated with increasing concentrations of halothane were statistically significant (P less than 0.05), the increase in frequency associated with isoflurane was not, although it was sufficient to maintain the end-tidal and arterialized venous PCO2 in the isoflurane group at a value which did not differ significantly from that in the halothane group. Profound depression of ventilation was produced in the children by enflurane, clearly because no increase in ventilatory frequency was associated with its use. It was evident that the ventilatory effects of the three volatile agents in unstimulated children are very similar to those described elsewhere in the adult. There was no difference of any clinical significance between the degree of depression of ventilation produced by halothane and isoflurane in children. PMID- 3105565 TI - Double-blind study of the reversal of midazolam-supplemented general anaesthesia with Ro 15-1788. AB - The actions and side effects of the benzodiazepine antagonist Ro 15-1788 were evaluated in a randomized double-blind clinical study in which midazolam was used as an anaesthetic agent. Sixty women who underwent laparoscopy were treated with Ro 15-1788 or with placebo after the surgical procedure. Ro 15-1788 reversed the hypnotic effect of midazolam within a few minutes. The patients were alert, co operative, oriented and had good recall of events after awakening. The effects were statistically better than placebo for up to 30 min after administration. Arterial pressure and heart rate remained stable and there were no significant side effects. The availability of Ro 15-1788 allows effective reversal of midazolam when this is used during general anaesthesia. PMID- 3105566 TI - Reversal of midazolam sedation with anexate. AB - Anexate (Ro 15-1788) a specific benzodiazepine antagonist, was assessed for its action in reversing midazolam-induced sedation. Sixty-five patients undergoing prostatic surgery under subarachnoid anaesthesia received midazolam for intraoperative sedation (mean dose 16 mg) followed by either active drug (anexate) or placebo given as a randomized, double-blind i.v. injection. The anexate dose sufficient to reverse sedation (0.36 +/- 0.09 mg), produced immediate and dramatic improvements in ability to comprehend and obey commands, in orientation in time and space and in degree of anterograde amnesia. These changes remained significantly different from the control group for 60 min after injection. There was no effect on arterial pressure, heart rate or ventilatory rate and no anxiety states were observed. After initial complete awakening, sedation increased gradually in drug-treated patients, while in the control group, sedation scores and cognitive testing scores all diminished over the 4-h study period. Anexate used in doses up to 0.5 mg provided safe and effective antagonism of midazolam-induced sedation in a clinical setting. PMID- 3105567 TI - Assessment of a high frequency ventilator breathing system for use in the operating theatre. An experimental and clinical study. AB - A breathing system capable of delivering positive pressure ventilation to the lungs at high frequencies and using anaesthetic gases and vapours is assessed. The recommended fresh gas flow at the ventilatory rates tested in this study was 100 ml kg-1. At 80 and 100 b.p.m. the system provided adequate ventilation, good oxygenation and haemodynamic stability. When compared with conventional positive pressure ventilation (CPPV), peak airway pressure (peak Paw) was lower and mean airway pressure (Paw) was lower (80 b.p.m.) or unchanged (100 b.p.m.). There was some inherent positive end-expiratory pressure (PEEP) associated with the technique. PMID- 3105568 TI - Comparative haemodynamic effects of intravenous lignocaine, disopyramide and flecainide in uncomplicated acute myocardial infarction. AB - A prospective study evaluated the comparative haemodynamic effects of three Class I antiarrhythmics (lignocaine Class 1B, disopyramide Class 1A and flecainide Class 1C) in 30 patients with uncomplicated acute myocardial infarction. Three groups, each of 10 patients, were allocated to lignocaine (Group I) 1.5 mg kg-1 i.v. loading dose over 10 min followed by infusion at 3 mg kg-1 h-1, disopyramide (Group II) or flecainide (Group III), both administered as a 1.0 mg kg-1 i.v. loading bolus over 10 min followed by a 1.6 mg kg-1 h-1 infusion for 120 min. The plasma levels of each drug were in the described therapeutic range. Lignocaine decreased cardiac index (-0.3 l min-1 m-2 (9%); P less than 0.05) and stroke volume index (-5 ml m-2 (11%); P less than 0.01). Systemic blood pressure, heart rate and systemic vascular resistance index were unchanged. There was a small increase (+3 mm Hg (30%); P less than 0.01) in pulmonary artery occluded pressure (PAOP). Both disopyramide and flecainide increased systemic blood pressure; the maximum increases for mean blood pressure were +10 mm Hg (11%) and +4 mm Hg (4%) respectively. Both drugs reduced cardiac index (-0.5 l min-1 m-2 (16%): -0.4 l min-1 m-2 (11%)) and stroke volume index (-11 ml m-2 (25%): -5 ml m-2 (11%)). There were increases in heart rate (+13: +5 beats min-1) pulmonary artery occluded pressure (+2: +3 mm Hg) and systemic vascular resistance index (+696: +275 dyn s cm-5 m2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105569 TI - Glyceryl-1-nitrate pharmacokinetics in healthy volunteers. AB - The plasma kinetics and urinary excretion of glyceryl-1-nitrate (G-1-N), a metabolite of glyceryl trinitrate with antianginal potential, were investigated in 10 healthy male volunteers, after intravenous infusion and oral administration of 20 mg G-1-N. The apparent volume of G-1-N distribution was 601 corresponding to 0.761 kg-1 body weight, on average. It is suggested that total body water is the principal biological correlate of the hydrophilic drug. Mean intravenous clearance was 283 ml min-1 or 3.61 ml min-1 kg-1. The average of elimination half lives were 2.50 +/- 0.36 (s.d.) h after the intravenous and 2.54 +/- 0.40 (s.d.) h after the oral dose. Inter-subject variances of pharmacokinetic parameters were low compared to variances reported for glyceryl trinitrate. The coefficient of intra-subject variation of the elimination half-lives was 8.8%. 5.5% (i.v.) and 5.4% (p.o.) of the administered dose were excreted into urine up to 48 h after the administration. 1% (i.v.) and 1.5% (p.o.) were in the conjugated form. The oral dose was rapidly and almost completely absorbed. The oral bioavailability on the basis of areas under the curve amounted to 88.6% on the average. For clinical use, owing to its high oral bioavailability, long residence in the body, inactivation by metabolic conversion, and good predictability of kinetic parameters, G-1-N offers advantage over glyceryl trinitrate. PMID- 3105571 TI - Twenty-first Paterson symposium: bioactivation of quinone anti-tumor agents. PMID- 3105570 TI - Cytotoxic effects of tumour necrosis factor and gamma-interferon on acute myeloid leukaemia blasts. AB - We have studied the cytotoxic effects of recombinant tumour necrosis factor and recombinant gamma interferon on primary cultures of leukaemia cells. The agents were added alone or in a combination to cells from 17 patients. Eleven had acute myeloblastic leukaemia (6 at presentation, 5 at relapse), 4 had acute lymphoblastic leukaemia, one had hairy cell leukaemia, and 2 had chronic myeloid leukaemia--one of whom was in myeloid blast transformation. Cells from patients with lymphoid malignancies or from the patient with chronic phase CML were not affected by either agent in any dose combination. In contrast, reduction of viability of myeloid blasts was weakly accelerated by TNF and gamma-interferon individually. Combination of the agents invariably produced enhanced killing and additive or synergistic effects were seen when 20-500 IU ml-1 of each cytokine was present. This sensitivity was also shown by blast cells from 5 patients with relapsed AML. We therefore suggest that trials of such combination therapy may be indicated in drug resistant or relapsed AML. PMID- 3105572 TI - Conjugal exposure to polychlorinated biphenyls (PCBs). PMID- 3105573 TI - Clinical and microbiological investigation of women with acute salpingitis and their consorts. PMID- 3105574 TI - Modification of synthetic peptides related to lactate dehydrogenase (231-242) by protein carboxyl methyltransferase and tyrosine protein kinase: effects of introducing an isopeptide bond between aspartic acid-235 and serine-236. AB - The possibility that isoaspartyl residues contribute to the substrate specificity of eucaryotic protein carboxyl methyltransferases and/or tyrosine protein kinases has been investigated with two synthetic oligopeptides, Lys-Gln-Val-Val Asp/isoAsp-Ser-Ala-Tyr-Glu-Val-Ile-Lys, which correspond to amino acids 231-242 of lactate dehydrogenase. One version of the peptide contains the normal amino acid sequence of the chicken muscle M4 isozyme. The other version contains an isoaspartyl residue in position 235 in place of the normal aspartyl residue; i.e., Asp-235 is linked to Ser-236 via its side-chain beta-carboxyl group, rather than via the usual alpha-carboxyl linkage. The normal peptide corresponds to the sequence around Tyr-238 that is phosphorylated in Rous sarcoma virus infected chick embryo fibroblasts [Cooper, J. A., Esch, F. S., Taylor, S. S., & Hunter, T. (1984) J. Biol Chem. 259, 7835]. Using protein carboxyl methyltransferase purified from bovine brain, we found that the normal peptide did not serve as a methyl-accepting substrate but that the isopeptide served as an excellent substrate, exhibiting a stoichiometry of one methyl group per peptide and Km of 0.54 microM. With tyrosine protein kinase partially purified from normal rat spleen both peptides were found to serve as phosphate acceptors at Tyr-238, exhibiting Km values of 4.7 and 8.9 mM for the normal and isopeptide versions, respectively. These results support the idea that protein carboxyl methyltransferase selectively methylates the alpha-carboxyl group of atypical isoaspartyl residues. In contrast, the presence of isoaspartate had a modest negative effect on substrate activity for a tyrosine protein kinase from rat spleen. PMID- 3105576 TI - NMR studies of the interaction of chromomycin A3 with small DNA duplexes I. AB - 1H and 31P NMR spectral analysis of a chromomycin/d(ATGCAT)2 complex provides strong evidence for a nonintercalative mode of drug binding. Investigation of the imino proton region of the duplex suggests a protection of one of the two guanine imino protons from fast exchange with the bulk water up to at least 45 degrees C by the drug. Subsequent one-dimensional nuclear Overhauser enhancement experiments place the exchangeable chromomycin chromophoric hydroxyl proton less than 0.45 nm from this guanine imino proton and the chromophore 7-methyl less than 0.45 from the internal thymine 6-proton and/or the guanine 8-proton. 1H two dimensional NMR reveals that the duplex retains a right-handed B conformation but there are distortions at the TGC region of one chain and large deviations in the chemical shift of protons relative to the uncomplexed duplex in the other chain in the same TGC region. The data suggest that the chromomycin chromophore is oriented such that the hydrophilic side of the ring system is proximal to the helix center in the major groove near the TG region while the aromatic side of the ring is oriented away from the helix but is partially protected from the solvent by the aliphatic chain, which bends back over the two aromatic protons. Changes in the 31P spectrum of the duplex on binding of the drug are different from the effect of either actinomycin or netropsin on nucleic acid fragments. PMID- 3105575 TI - Transduction proteins of olfactory receptor cells: identification of guanine nucleotide binding proteins and protein kinase C. AB - We have analyzed guanine nucleotide binding proteins (G-proteins) in the olfactory epithelium of Rana catesbeiana using subunit-specific antisera. The olfactory epithelium contained the alpha subunits of three G-proteins, migrating on polyacrylamide gels in SDS with apparent molecular weights of 45,000, 42,000, and 40,000, corresponding to Gs, Gi, and Go, respectively. A single beta subunit with an apparent molecular weight of 36,000 was detected. An antiserum against the alpha subunit of retinal transducin failed to detect immunoreactive proteins in olfactory cilia detached from the epithelium. The olfactory cilia appeared to be enriched in immunoreactive Gs alpha relative to Gi alpha and Go alpha when compared to membranes prepared from the olfactory epithelium after detachment of the cilia. alpha subunits of G-proteins were not detected in cilia detached from the nonchemosensory respiratory epithelium of the palate. Immunohistochemical studies using an antiserum against the beta subunit of G-proteins revealed intense staining of the ciliary surface of the olfactory epithelium and of the axon bundles in the lamina propria. In contrast, an antiserum against a common sequence of the alpha subunits preferentially stained the cell membranes of the olfactory receptor cells and the acinar cells of Bowman's glands and the deep submucosal glands. Prolonged incubation periods with these antisera tended to obliterate these differences in staining patterns, giving rise to staining by both antisera of the ciliary surface, the olfactory receptor cell membranes, the axon bundles, and the acinar cells of the glands. In addition to G-proteins, we have identified protein kinase C in olfactory cilia via a protein kinase C specific antiserum and via phorbol ester binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105577 TI - Epidermal growth factor dependent phosphorylation of a 35-kilodalton protein in placental membranes. AB - In human placental membranes isolated in the presence of ethylenediaminetetraacetic acid (EDTA), epidermal growth factor (EGF) stimulated the [gamma-32P]ATP-dependent phosphorylation of tyrosine residues on the 170 kilodalton (kDa) EGF receptor and on a 35-kDa protein. The initial rate of phosphorylation of these proteins in the presence of EGF was 5.2 and 3.5 nmol of phosphate min-1 (mg of receptor protein)-1, and this was approximately 10- and 6 fold higher than the basal rate, respectively. Half-maximal phosphorylation of both proteins occurred at about 2.5 nM EGF. In the presence of p-nitrophenyl phosphate, EGF stimulated the phosphorylation of the 35-kDa protein but not the EGF receptor, suggesting that hormone-stimulated autophosphorylation of the receptor/kinase was not required for kinase activation. The 35-kDa protein exists in two forms: (1) 35Keluate, which was associated with the membrane in the presence of Ca2+ but was eluted with EDTA, and (2) 35Kmemb, which was not eluted from membranes with EDTA. Both forms were immunologically related to a 35-kDa protein previously isolated from A431 cells. Antiserum against the 35-kDa protein also reacted with a protein with an apparent size of 66 kDa that was phosphorylated in an EGF-dependent manner. In phosphorylation reactions performed in the presence of Mg2+, Ca2+ was required for phosphorylation of the 35Keluate form, but Ca2+ was not required for phosphorylation of the 35Kmemb form. Phosphorylation appears to change the membrane-binding properties of the 35Kmemb form because 32P-labeled 35Kmemb could be eluted from the membrane by EDTA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105578 TI - Chemical modification of 3 alpha,20 beta-hydroxysteroid dehydrogenase with diethyl pyrocarbonate. Evidence for an essential, highly reactive, lysyl residue. AB - Diethyl pyrocarbonate inactivated the tetrameric 3 alpha,20 beta-hydroxysteroid dehydrogenase with second-order rate constants of 1.63 M-1 s-1 at pH 6 and 25 degrees C or 190 M-1 s-1 at pH 9.4 and 25 degrees C. The activity was slowly and partially restored by incubation with hydroxylamine (81% reactivation after 28 h with 0.1 M hydroxylamine, pH 9, 25 degrees C). NADH protected the enzyme against inactivation with a Kd (10 microM) very close to the Km (7 microM) for the coenzyme. The ultraviolet difference spectrum of inactivated vs. native enzyme indicated that a single histidyl residue per enzyme subunit was modified by diethyl pyrocarbonate, with a second-order rate constant of 1.8 M-1 s-1 at pH 6 and 25 degrees C. The histidyl residue, however, was not essential for activity because in the presence of NADH it was modified without enzyme inactivation and modification of inactivated enzyme was rapidly reversed by hydroxylamine without concomitant reactivation. Progesterone, in the presence of NAD+, protected the histidyl residue against modification, and this suggests that the residue is located in or near the steroid binding site of the enzyme. Diethyl pyrocarbonate also modified, with unusually high reaction rate, one lysyl residue per enzyme subunit, as demonstrated by dinitrophenylation experiments carried out on the treated enzyme. The correlation between inactivation and modification of lysyl residues at different pHs and the protection by NADH against both inactivation and modification of lysyl residues indicate that this residue is essential for activity and is located in or near the NADH binding site of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105579 TI - Molecular cloning and sequence analysis of complementary DNA encoding rat mammary gland medium-chain S-acyl fatty acid synthetase thio ester hydrolase. AB - Poly(A)+ RNA from pregnant rat mammary glands was size-fractionated by sucrose gradient centrifugation, and fractions enriched in medium-chain S-acyl fatty acid synthetase thio ester hydrolase (MCH) were identified by in vitro translation and immunoprecipitation. A cDNA library was constructed, in pBR322, from enriched poly(A)+ RNA and screened with two oligonucleotide probes deduced from rat MCH amino acid sequence data. Cross-hybridizing clones were isolated and found to contain cDNA inserts ranging from approximately 1100 to 1550 base pairs (bp). A 1550-bp cDNA insert, from clone 43H09, was confirmed to encode MCH by hybrid select translation/immunoprecipitation studies and by comparison of the amino acid sequence deduced from the DNA sequence of the clone to the amino acid sequence of the MCH peptides. Northern blot analysis revealed the size of the MCH mRNA to be 1500 nucleotides, and it is therefore concluded that the 1550-bp insert (including G X C tails) of clone 43H09 represents a full- or near-full length copy of the MCH gene. The rat MCH sequence is the first reported sequence of a thioesterase from a mammalian source, but comparison of the deduced amino acid sequences of MCH and the recently published mallard duck medium-chain S-acyl fatty acid synthetase thioesterase reveals significant homology. In particular, a seven amino acid sequence containing the proposed active serine of the duck thioesterase is found to be perfectly conserved in rat MCH. PMID- 3105580 TI - Affinity selection of chemically modified proteins: role of lysyl residues in the binding of calmodulin to calcineurin. AB - In affinity selection, calcineurin selects from a population of randomly modified calmodulins those species with which it prefers to interact. The method shows that acetylation of lysines affects calmodulin so as to interfere with its ability to interact with calcineurin. Monoacetylation of any lysine of calmodulin reduces its affinity for calcineurin by 5-10-fold. Multiple acetylations amplify the loss of affinity; none of the modifications are imcompatible with activity. The lack of selectivity of calcineurin against any particular modified lysine indicates that the loss of affinity reflects changes induced by the removal of the charged groups and suggests an important role for electrostatic interactions in the cooperative structural transitions which calmodulin undergoes upon binding its target proteins or calcium. In the presence of calcineurin, a large and specific decrease in the rate of acetylation of Lys-75 and -148 of calmodulin is observed. The reactivity of the same residues is greatly increased in the presence of calcium alone [Giedroc, D. P., Sinha, S. K., Brew, K., & Puett, D. (1985) J. Biol. Chem. 260, 13406-13413]. Lys-75, located in the central helix, and the C-terminal Lys-148 [Babu, Y. S., Sacks, J. S., Greenhouse, T. J., Bugg, C. E., Means, A. R., & Cook, W. J. (1985) Nature (London) 315, 37-40] may act as sensors of the calmodulin allosteric transitions. Their reactivity changes in opposite directions in response to calcium-induced or calcineurin-induced structural changes. The reactivity of other residues such as Lys-21, decreased in the presence of calcineurin but not calcium, is also affected by a conformational change which is induced specifically by calcineurin. PMID- 3105581 TI - Homologues of the human C and A apolipoproteins in the Macaca fascicularis (cynomolgus) monkey. AB - We used antisera to human A and C apolipoproteins to identify homologues of these proteins among the high-density lipoprotein apoproteins of Macaca fascicularis (cynomolgus) monkeys, and NH2-terminal analysis was used to verify the homology. The NH2-terminal sequence of the M. fascicularis apoA-I is identical with that of another Old World species, Erythrocebus patas, and differs from human apoA-I at only 4 of the first 24 residues. M. fascicularis apoA-II contains a serine for cysteine replacement at position 6 and is therefore monomeric like the apoA-II from all species below apes. Human and monkey apoA-II are not otherwise different through their first 25 residues. About 20% of M. fascicularis apoC-I aligns with human apoC-I through residue 22, and 80% lacks an NH2-terminal dipeptide. Otherwise, the monkey apoC-I differs from the human protein at only 2 of 25 positions. Two forms of M. fascicularis apoC-II were identified. ApoC-II1 is highly homologous with human apoC-II, whereas an NH2-terminal hexapeptide is absent from apoC-II2. ApoC-II2 was the predominant species, and apoC-II1 appears to represent a propeptide from which a hexapeptide prosegment is cleaved at a Gln Asp bond. Both forms of monkey apoC-II are potent activators of lipoprotein lipase. There are two polymorphic forms of M. fascicularis apoC-III, and their electrophoretic mobilities become identical after treatment with neuraminidase. Except for a glycine for serine substitution at position 10, the first 15 NH2 terminal residues of M. fascicularis and human apoC-III are the same. PMID- 3105582 TI - Genetic analysis of the form and function of the viral src oncogene product. PMID- 3105583 TI - Cell-free translation products of basement membrane RNA from the EHS tumor. AB - The biosynthetic products of the Engelbreth-Holm-Swarm (EHS) tumor and the cell free translation products of EHS tumor cell RNA were characterized. Six distinct gene products (three laminin polypeptides, entactin/nidogen, and two collagen IV chains) comprising the basement membrane matrix were identified by a combination of proteolytic digestion and immunologic techniques. Analysis of the cell-free translation products using EHS tumor RNA precipitated by anti-laminin serum confirms earlier evidence that there are at least two B chains encoded by different genes. The anti-laminin serum also recognized entactin/nidogen, which was further identified by specific immunoprecipitation with anti-entactin serum. Radiolabeled laminin A chains, synthesized by the EHS tumor in organ culture, were also identified by the anti-laminin serum but were not detected among the cell-free translation products of EHS tumor RNA. Pulse-chase studies of EHS tumor in organ culture as well as in vitro translation of EHS tumor RNA suggest that the precursor forms of alpha 1(IV) and alpha 2(IV) collagen chains are nearly identical in size, with apparent molecular weights of 170,000. The mRNAs encoding these two polypeptides migrate differently on sucrose gradients. It is likely that glycosylation and hydroxylation of collagen IV account for the major differences in molecular weight of mature alpha 1(IV) and alpha 2(IV) chains in the EHS tumor matrix. PMID- 3105585 TI - Kinetic study on the suicide inactivation of tyrosinase induced by catechol. AB - Tyrosinase has a suicide inactivation reaction when it acts on omicron-diphenols. In the present paper, this reaction has been studied using a transient phase approach. Explicit equations of product vs. time have been developed for the multisubstrate mechanism of tyrosinase, and the kinetic parameters which characterize the enzyme acting on the suicide substrate catechol have been determined. The effect of pH has also been considered. PMID- 3105584 TI - The effects of phosphatase on the components of the cytochrome P-450-dependent microsomal monooxygenase. AB - Incubation of rabbit liver microsomes with alkaline phosphatase resulted in a marked decrease of NADPH-dependent monooxygenase activities. This decrease was found to be correlated with the decrease of NADPH-cytochrome c reductase activity catalyzed by NADPH-cytochrome P-450 reductase. Neither the content of cytochrome P-450, as determined from its CO difference spectrum, nor the peroxide-supported demethylase activity catalyzed by cytochrome P-450 alone was affected by the phosphatase treatment. NADH-cytochrome b5 reductase and cytochrome b5 were not affected by the phosphatase either. NADPH-cytochrome P-450 reductase purified from rabbit liver microsomes lost its NADPH-dependent cytochrome c reductase activity upon incubation with phosphatase in a way similar to that of microsome bound reductase. Flavin analysis showed that the phosphatase treatment caused a decrease of FMN with concomitant appearance of riboflavin. Alkaline phosphatase, therefore, inactivates the reductase by attacking its FMN, and the inactivation of the reductase, in turn, leads to a decrease of the microsomal monooxygenase activities. PMID- 3105586 TI - Studies of the modulation of essential fatty acid metabolism by fatty acids in cultured neuroblastoma and glioma cells. AB - In cultured neuroblastoma cells (N1E-115), the metabolism of the essential fatty acid, linoleic acid (18:2 (n-6)), to arachidonic acid (20:4(n-6)) can be altered by other fatty acids in a manner supporting a concerted action of the modulating fatty acid on the desaturation and chain elongation enzymes. In further examination of mechanisms involved, cultured glioma (C-6) or neuroblastoma-glioma hybrids (NG-108-15) cells showed similar patterns of activation by some fatty acids (e.g., 20:3(n-6) and 20:4(n-6)), and inhibition (e.g., 18:3(n-3) or 22:6(n 3)) or no effect (e.g., 18:1(n-9), 20:3(n-3)) by others. In contrast, only inhibition by 20:4(n-6) was seen in cultured HeLa cells, suggesting that the intracellular interactions may not be universal in all cell lines. For fatty acids that activate 20:4(n-6) formation, the lag observed when substrate and activator were administered simultaneously was eliminated by preincubation with activator. Maximal activation occurred within 4 h for neuroblastoma and 2 h for glioma; in each cell line activation declined steadily for 10 h after removal of the activator. Inhibition of protein synthesis did not alter activation. As 98% of the fatty acid incorporated was esterified to triacylglycerol or phospholipid and only the triacylglycerol mass expanded, several manipulations to potentially alter the flow of acyl chains between these lipid pools were evaluated using dual label and pulse-chase experiments. Results suggested that competition between 18:2(n-6) utilization for esterification to phospholipid and the desaturation chain elongation sequence as well as a more direct and specific interaction of certain fatty acids with the enzymes may influence 20:4(n-6) formation. A model to explain these observations is discussed. PMID- 3105587 TI - A method to screen apolipoprotein polymorphisms in whole plasma: description of apolipoprotein A-IV variants in dyslipidemias and a reassessment of apolipoprotein A-I in Tangier disease. AB - A sensitive and rapid immunological detection method was used to screen for apolipoprotein A-IV variants. Antibodies to human lymph chylomicron or plasma apolipoprotein A-IV, and plasma apolipoprotein A-I were raised in rabbits. Antibodies to apolipoprotein A-I or apolipoprotein A-IV were shown to be monospecific to their respective antigens by reactivity against human chylomicron apolipoproteins by immunoblot analysis. Plasma samples were obtained from dyslipidemic subjects from the Lipid Research Clinic of Columbia University. The plasma samples were isoelectrically focused (pH 4-6) on slab gels. Plasma proteins were then transferred to nitrocellulose paper for immunoblotting. Apolipoprotein A-IV polymorphism was determined by specific immunological detection of apolipoprotein A-IV. Identical apolipoprotein A-IV isoprotein patterns were observed when either antibodies to lymph or plasma apolipoprotein A IV were used for immunoblotting. All the dyslipidemic plasma samples screened contained the two major and one or two minor isoproteins of normal plasma. In two instances, new apolipoprotein A-IV variants having an additional isoform were detected. One subject was hypertriglyceridemic (triacylglycerols = 342 mg/dl, cholesterol = 251 mg/dl) and had an additional major acidic apolipoprotein A-IV isoform. Another subject with mild hypocholesterolemia (triacylglycerols = 209 mg/dl, cholesterol = 120 mg/dl) was found to have additional major and minor basic apolipoprotein A-IV isoforms. The specificity of this technique allows detection of polymorphism of apolipoproteins of similar isoelectric points by use of a single dimension isoelectric focusing gel. This technique also demonstrated the presence of altered apolipoprotein A-I isoforms in the plasma of a patient with Tangier disease. These isoforms were previously identified as isoforms 2 and 4 of normal plasma by use of two-dimensional gel electrophoresis. However, by use of this new technique and careful evaluation of previously published two dimensional gels, we now identify these apolipoprotein A-I isoforms as being more acidic than those of normal plasma. PMID- 3105588 TI - Distribution of phospholipid molecular species containing arachidonic acid and cholesterol in V79-UF cells. AB - V79-UF cells were isolated from Chinese hamster V79 cells as a cell line that requires exogenous unsaturated fatty acids for growth. V79-UF cells incorporated arachidonic acid into phospholipids. The molecular species of diacyl phosphatidylcholine and phosphatidylethanolamine containing arachidonic acid comprised 61.4 and 70.5% of the total phospholipid molecular species in total membranes and 58.1 and 64.7% in plasma membrane, respectively. Polyunsaturated molecular species were distributed in a higher amount in the intracellular membranes than in the plasma membrane. No significant difference was seen in the diffusion coefficient between the plasma membranes from cells supplemented with oleic and arachidonic acids in spite of a distinct difference in the degree of unsaturation between the molecular species of these plasma membranes. The amount of cholesterol in the plasma membrane was higher in the cells grown in the presence of arachidonic acid than in those grown in the presence of oleic acid. PMID- 3105590 TI - Human neutrophils incorporate arachidonic acid and saturated fatty acids into separate molecular species of phospholipids. AB - The incorporation of radiolabeled arachidonic acid and saturated fatty acids into choline-linked phosphoglycerides (PC) of rabbit and human neutrophils was investigated by resolving the individual molecular species by reversed-phase high performance liquid chromatography. PC from neutrophils incubated with a mixture of [3H]arachidonic acid and [14C]stearic or [14C]palmitic acid contains both radiolabels; however, double labeling of individual molecular species is minimal. After labeling for 2 h, the [3H]arachidonate is distributed almost equally between diacyl and 1-O-alkyl-2-acyl species, but it is incorporated into diacyl species containing unlabeled stearate or palmitate at the sn-1 position. In contrast, labeled saturated fatty acids are incorporated only into diacyl species and contain predominantly oleate and linoleate at the sn-2 position. Labeled linoleate is not incorporated into ether-linked species, but is found in the same species as labeled stearate. The findings suggest that mechanisms exist in neutrophils for specific shunting of exogenous arachidonic acid into certain phospholipid molecular species and support the concept that the 1-O-alkyl-2 arachidonoyl species may be a functionally segregated pool of arachidonic acid within the PC of neutrophils. PMID- 3105589 TI - Inhibition of arachidonic acid oxidation by beta-carotene, retinol and alpha tocopherol. AB - Prostaglandin and hydroxyeicosatetraenoic acid (HETE) production from arachidonic acid in bovine seminal vesicles and kidney as influenced by the addition of beta carotene, retinol or alpha-tocopherol was studied. The major product formed was prostaglandin E2 (approximately 85% prostaglandin E2 of control), and its proportion decreased with increasing concentration of the additives, while the proportion of HETE increased. Prostaglandin and HETE production was considerably inhibited by beta-carotene and retinol, and to a lesser extent by alpha tocopherol; HETE production was inhibited less than that of prostaglandin. It appears that beta-carotene, retinol and alpha-tocopherol influence both the cyclooxygenase and lipoxygenase pathways; this modulation of arachidonic acid oxidation by physiological compounds may have important in vivo implications. PMID- 3105591 TI - Distribution, purification and characterization of rat intestinal UDPgalactose: N acetylglucosaminyl(beta 1----4)galactosyltransferase. AB - Rat intestinal UDPgalactose: N-acetylglucosaminyl(beta 1--- 4)galactosyltransferase activity was studied as to its intestinal and villus-to crypt distribution, and then purified and characterized. Rapid UDPgalactose hydrolysis was noted in the duodenum and jejunum; little to no breakdown was detected in the distal ileum, cecum and proximal colon. Product analysis suggested that UDPgalactose hydrolysis was due to nucleotide-sugar pyrophosphatase and galactose-1-phosphate phosphatase activities; ileum appeared to have little of the first activity and none of the latter. An aboral gradient of galactosyltransferase activity was noted, activity being 3-4-fold higher in the ileum, cecum and proximal colon. Total homogenate exogenous acceptor galactosyltransferase activities showed no villus-crypt differences but activity measured with intact isolated cells demonstrated higher activity with crypt cells; this was particularly evident in the ileum. Galactosyltransferase activity was purified from ileal-colonic mucosa. An over 4000-fold purification with 75 percent yield was achieved. Only one band of approx. 70-75 kDa was noted on sodium dodecyl sulfate polyacrylamide electrophoresis. As with other eukaryotic galactosyltransferase activities, there was an absolute requirement for Mn2+; the concentration required for half maximal activity was only 2.5 microM and higher concentrations did not inhibit. The Km for UDPgalactose was 30 microM. PMID- 3105592 TI - The distribution and partial characterization of UDPgalactose: N acetylgalactosamine mucin galactosyltransferase activity from rat small intestine and its sensitivity to Zn2+. AB - UDPgalactose: N-acetylgalactosamine mucin galactosyltransferase activity of the rat intestine was studied and purified using asialo-ovine submaxillary mucin as the acceptor substrate and inhibitors to suppress UDPgalactose breakdown by pyrophosphatase activities particularly prevalent in the duodenal-jejunal regions. Despite adequate suppression of UDPgalactose breakdown, significant intestinal region differences of mucin galactosyltransferase activity were observed. Elevations of activity were observed in the duodenum and distal ileum of the small intestine and the cecum and proximal colon; these elevations in activity correspond to areas of increased mucin production. Similarly, mucin galactosyltransferase activity of duodenal cells isolated along a crypt-to-villus axis showed a moderate increase (67.7%) in activity associated with cells in the crypt region. Small intestine mucin galactosyltransferase activity was purified 800-fold using a series of ion exchange (DEAE-Sepharose), gel filtration (S-200 Sephacryl) and affinity chromatographic steps to isolate the mucin galactosyltransferase activity from a Triton X-100/Nonidet P-40 extract of homogenized cells obtained by scraping everted intestines. The partially purified enzyme showed two distinct protein bands of 81.5 and 50 kDa and a faint band at 53.3 kDa. Kinetic analysis gave an apparent Km of 152 microM for UDPgalactose. The enzyme showed optimal activity with Mn2+ (20 mM) and partial activities using a number of other divalent cations. Higher concentrations of Mn2+ were slightly inhibitory. Mucin galactosyltransferase activity was inhibited by more then 90% in the presence of Zn2+ (4 mM) and this inhibition could not be reversed by additional Mn2+. Addition of Zn2+ (4 mM) to assays containing Mn2+ (20 mM) did not cause appreciable UDPgalactose breakdown, as measured by high-voltage paper electrophoresis, suggesting that Zn2+ inhibition is not a result of pyrophosphatase activation. In addition, Zn2+ does not appear to activate a protease or glycosidase activity in the partially purified enzyme preparation which could hydrolyze the galactosylated product prior to isolation. PMID- 3105593 TI - Mechanism of arachidonic acid-induced Ca2+ mobilization from rat liver microsomes. AB - Recent evidence indicates that unesterified arachidonic acid functions as a mediator of intracellular Ca2+ mobilization by inducing Ca2+ release from the endoplasmic reticulum of pancreatic islet beta cells in a manner closely similar to that of inositol 1,4,5-trisphosphate. To test the generality and explore the mechanism of this phenomenon we have examined the effects of arachidonic acid on calcium accumulation and release by hepatocyte subcellular fractions enriched in endoplasmic reticulum (microsomes). At concentrations above 0.017 mumol/mg microsomal protein, arachidonate induced rapid (under 2 min) 45Ca2+ release from microsomes that had been preloaded with 45Ca2+. Arachidonate also suppressed microsomal 45Ca2+ accumulation when present during the loading period, as reflected by reduction both of 45Ca2+ accumulation at steady state and of the rate of uptake. Neither the cyclooxygenase inhibitor indomethacin nor the lipoxygenase/cyclooxygenase inhibitor BW755C suppressed arachidonate-induced 45Ca2+ release, indicating that this effect was not dependent upon oxygenation of the fatty acid to metabolites. The long-chain unsaturated fatty acids oleate and linoleate were less potent than arachidonate in inducing 45Ca2+ release, and the saturated fatty acid stearate did not exert this effect. Albumin prevented 45Ca2+ release by arachidonate, presumably by binding the fatty acid. As is the case for inositol 1,4,5-trisphosphate, the ability of arachidonate to induce 45Ca2+ release was dependent on the ambient free Ca2+ concentration. Arachidonate did not influence microsomal membrane permeability or Ca2+-ATPase activity and may exert its effects on microsomal Ca2+ handling by activation of a Ca2+ extrusion mechanism or by dissociating Ca2+ uptake from Ca2+-ATPase activity. PMID- 3105594 TI - Effect of extracellular Ca2+ on plasma membrane Ca2+ inflow and cytoplasmic free Ca2+ in isolated hepatocytes. AB - An initial rapid phase and a subsequent slow phase of 45Ca2+ uptake were observed following the addition of 45Ca2+ to Ca2+-deprived hepatocytes. The magnitude of the rapid phase increased 15-fold over the range 0.1-11 mM extracellular Ca2+ (Ca2+o) and was a linear function of [Ca2+]o. The increases in the rate of 45Ca2+ uptake were accompanied by only small increases in the intracellular free Ca2+ concentration. In cells made permeable to Ca2+ by treatment with saponin, the rate of 45Ca2+ uptake (measured at free Ca2+ concentrations equal to those in the cytoplasm of intact cells) increased as the concentration of saponin increased from 1.4 to 2.5 micrograms per mg wet weight cells. Rates of 45Ca2+ uptake by cells permeabilized with an optimal concentration of saponin were comparable with those of intact cells incubated at physiological [Ca2+o], but were substantially lower than those for intact cells incubated at high [Ca2+o]. It is concluded that Ca2+ which enters the hepatocyte across the plasma membrane is rapidly removed by binding and transport to intracellular sites and by the plasma membrane (Ca2+ + Mg2+)-ATPase and the plasma membrane Ca2+ inflow transporter is not readily saturated with Ca2+o. PMID- 3105595 TI - Induction of histidine decarboxylase by dexamethasone in mastocytoma P-815 cells. AB - Dexamethasone at a concentration as low as 10 nM significantly increased both the histamine content and histidine decarboxylase activity of cultured mastocytoma P 815 cells. Both effects were clearly seen using several glucocorticoids, which were as effective as dexamethasone. In contrast to that of histamine, the serotonin level of mastocytoma P-815 cells was decreased by treatment with dexamethasone. The dexamethasone-induced increases in histamine content and histidine decarboxylase activity were completely suppressed by the addition of cycloheximide and actinomycin D. Mastocytoma P-815 cells were found to possess binding sites for [3H]dexamethasone in the cytosol (Kd = 15.7 nM) and the nuclei (Kd = 1.26 nM). These results show that glucocorticoids significantly stimulate de novo synthesis of histidine decarboxylase. PMID- 3105596 TI - Epidermal growth factor actions on arachidonic acid metabolism in human amnion cells. AB - Epidermal growth factor (EGF) from human and murine sources increased prostaglandin E2 production by human amnion cells. An anti-EGF receptor monoclonal antibody abolished this stimulatory action of EGF and reduced the basal rate of amnion prostaglandin E2 biosynthesis. The rates of formation of arachidonate lipoxygenase products were also enhanced by EGF. PMID- 3105597 TI - N-ethylmaleimide inhibits Ca2+ influx induced by collagen or arachidonate on rabbit platelets. AB - N-Ethylmaleimide dose dependently inhibited platelet aggregation induced by collagen or arachidonate but did not inhibit the aggregation by thrombin or ionophore A23187 within the concentrations tested. [3H]Arachidonate release from membrane phospholipids of the collagen-stimulated platelets was inhibited by N ethylmaleimide in parallel with the inhibition of aggregation, but not in response to A23187. N-Ethylmaleimide prevented 45Ca2+ influx into platelet cells from outer medium induced by collagen, and also inhibited the increase in the concentration of cytoplasmic free Ca2+, which probably results from Ca2+ influx, as monitored by quin2 fluorescence, under stimulation with arachidonate. The concentration of N-ethylmaleimide giving a complete inhibition of Ca2+ influx was consistent with that required to inhibit collagen- or arachidonate-induced aggregation. Prostaglandin metabolism from arachidonate to thromboxane A2 was not disturbed by N-ethylmaleimide, while phosphatidate formation induced by arachidonate was slightly inhibited by it at concentrations at which aggregation was completely inhibited. These data suggest that N-ethylmaleimide preferentially suppresses increase in cytoplasmic free Ca2+ which is linked to thromboxane A2 receptor occupation in collagen- or arachidonate-stimulated platelets, probably due to blockage of Ca2+ influx through Ca2+-channel protein, thereby inhibiting aggregation induced by these agonists. PMID- 3105598 TI - Ca2+-dependent translocation of hexose carrier in mouse fibroblast Swiss 3T3 cells. AB - Ca2+-induced translocation of hexose carriers from microsomal membrane to plasma membrane was demonstrated in saponin-permeabilized Swiss 3T3 cells by a specific D-glucose-inhibitable cytochalasin B-binding assay. The number of hexose carriers in the plasma membrane and the hexose transport activity in intact cells were also compared. The incubation of permeabilized cells with 10 microM Ca2+ at 37 degrees C rapidly increased the number of D-glucose-inhibitable cytochalasin B binding sites in the plasma membrane from 13 to 40 pmol/mg protein and concomitantly decreased that in the microsomal membrane from 66 to 36 pmol/mg protein, each with a half-time of approx. 2 min. Furthermore, when Ca2+ stimulated cells were exposed to 50 microM EGTA, the effect of Ca2+ on the translocation of D-glucose-inhibitable cytochalasin B-binding sites was reversed with a half-time of approx. 5 min. The concentration of Ca2+ required for the half-maximal effect was approx 500 nM. The magnitude of the stimulatory effect of D-glucose-inhibitable cytochalasin B-binding sites in the plasma membrane closely correlated with the magnitude of stimulatory action of Ca2+ on 3-O-methylglucose transport in the intact cells. These results suggest that Ca2+ regulates the activity of hexose transport across the plasma membrane through a rapid and reversible translocation of hexose carrier between microsomal and plasma membranes of mouse fibroblast Swiss 3T3 cells. PMID- 3105599 TI - Purification and properties of a multifunctional calcium/calmodulin-dependent protein kinase from rat pancreas. AB - A calcium/calmodulin-dependent protein kinase (Ca/calmodulin protein kinase) was purified from rat pancreas using hydrophobic chromatography followed by gel filtration and affinity chromatography. Ca/calmodulin protein kinase from pancreas resembled previously described multifunctional Ca/calmodulin protein kinases from other tissues with respect to substrate specificity, autophosphorylation on serine and threonine residues, and catalytic and hydrodynamic properties. While Ca/calmodulin protein kinase from other tissues contains subunits of 53-60 kDa with variable proportions of a smaller 50-52 kDa subunit, pancreatic Ca/calmodulin protein kinase was found to contain a single component of 51 kDa. Experiments mixing brain Ca/calmodulin protein kinase with pancreatic homogenate suggest that the absence of a larger subunit in the pancreatic Ca/calmodulin protein kinase is not due to proteolytic degradation during enzyme preparation. Ca/calmodulin protein kinase binding to 125I-labeled calmodulin in solution was demonstrated using the photoaffinity cross-linker, N hydroxysuccinimidyl-4-azidobenzoate. 125I-labeled calmodulin binding to Ca/calmodulin protein kinase was also demonstrated using filters containing Ca/calmodulin protein kinase transferred from polyacrylamide gels after two dimensional gel electrophoresis. Finally, the ribosomal substrate for Ca/calmodulin protein kinase was identified as the ribosomal protein, S6. The purification procedure presented in this study promises to be useful in characterizing Ca/calmodulin protein kinase in other tissues and in clarifying the role of these enzymes in cellular function. PMID- 3105600 TI - Regulatory properties of pigeon heart muscle AMP deaminase. AB - The kinetic and regulatory properties of purified pigeon heart muscle AMP deaminase were investigated. In the presence of 100 mM potassium chloride, the enzyme exhibited a slightly sigmoidal type of kinetics. Addition of ATP to the incubation medium changed the reaction rate versus substrate concentration plot into a hyperbolic one, and caused a decrease of the half-saturation constant (S0.5). ADP presence caused the change of both the S0.5 and Vmax parameters, exerting either an activating or inhibitory effect, depending upon the substrate concentration. Orthophosphate inhibited the enzyme at all substrate concentrations, increasing the value of the S0.5 parameter. In the presence of ATP, ADP and orthophosphate, added to the incubation medium at approximately physiological concentrations, pigeon heart AMP deaminase still seems to preserve its activated form. Active long chain fatty acids clearly inhibited enzyme activity even at micromolar concentrations. Interpretation of the kinetic data in terms of the allosteric theory of Monod et al. (1965, J. Mol. Biol. 12, 88-118) indicates that heart muscle AMP deaminase may operate as a functionally active dimer. PMID- 3105601 TI - Platelet derived growth factor is present in human placenta: purification from an industrially processed fraction. AB - Platelet derived growth factor was purified from an industrially processed fraction of human placenta (EAP) donated by the Institut Merieux. We first demonstrated that EAP contains PDGF and the quantity of this growth factor was estimated by inhibition of its biological activity using antibodies against PDGF. According to this first estimation, 1 l of EAP (obtained from 125 kg of placenta) contains 10-1000 micrograms of PDGF. A purification procedure including fast flow chromatography (cationic S), heparin Sepharose affinity, chromatography on Cibacron Blue followed by a reverse phase on a C8 column gave a 6000-fold enrichment with a yield of 14%. This result suggests that the PDGF content in 1 l of EAP is between 10 and 30 micrograms. Mitogenic activity was measured on human fibroblast AG1523, Chinese hamster fibroblasts CCL39 and bovine epithelial cells BEC. Dose-response curves indicate that our preparation of purified PDGF from human placenta induces 50% of the maximal tritiated thymidine incorporation in CCL39 at a dose of 5 ng of PDGF/ml of culture medium. PMID- 3105602 TI - The complete amino acid sequence of the human aldolase C isozyme derived from genomic clones. AB - The complete protein sequence of the human aldolase C isozyme has been determined from recombinant genomic clones. A genomic fragment of 6673 base pairs was isolated and the DNA sequence determined. Aldolase protein sequences, being highly conserved, allowed the derivation of the sequence of this isozyme by comparison of open reading frames in the genomic DNA to the protein sequence of other human aldolase enzymes. The protein sequence of the third aldolase isozyme found in vertebrates, aldolase C, completes the primary structural determination for this family of isozymes. Overall, the aldolase C isozyme shared 81% amino acid homology with aldolase A and 70% homology with aldolase B. The comparisons with other aldolase isozymes revealed several aldolase C-specific residues which could be involved in its function in the brain. The data indicated that the gene structure of aldolase C is the same as other aldolase genes in birds and mammals, having nine exons separated by eight introns, all in precisely the same positions, only the intron sizes being different. Eight of these exons contain the protein coding region comprised of 363 amino acids. The entire gene is approximately 4 kilobases. PMID- 3105604 TI - One step purification of Escherichia coli beta-glucuronidase. AB - beta-glucuronidase was purified by affinity chromatography on thiophenyl glucuronide coupled to Sepharose. The enzyme was more than 95% pure. This enzyme is a tetramer composed of identical 74 kDa monomers. The amino-terminal sequence determined was: NH2-Met-Leu-Arg-Pro-Val. PMID- 3105603 TI - Monoclonal antibodies against acetylcholinesterase from electric organs of Electrophorus and Torpedo. AB - We studied the reactivity of monoclonal antibodies (mAbs) raised against acetylcholinesterase (AChE) purified from Electrophorus and Torpedo electric organs. We obtained IgG antibodies (Elec-21, Elec-106, Tor-3E5, Tor-ME8, Tor 1A5), all of them directed against the catalytic subunit of the corresponding species, with no significant cross-reactivity. These antibodies do not inhibit the enzyme and recognize all molecular forms, globular (G) and asymmetric (A). Tor-ME8 reacts specifically with the denatured A and G subunits of Torpedo AChE, in immunoblots. Several hybridomas raised against Electrophorus AChE produced IgM antibodies (Elec-39, Elec-118, Elec-121). These antibodies react with the A forms of Electrophorus electric organs and also with a subset of dimers (G2) from Torpedo electric organ. In addition, they react with a number of non-AChE components, in immunoblots. In contrast, they do not recognize AChE from other Electrophorus tissues or A forms from Torpedo electric organs. PMID- 3105605 TI - Proteolytic events in the post-translational processing of polypeptide hormone precursors. PMID- 3105607 TI - [Characteristics of 3,4-benzopyrene-induced cytochrome P-448 forms isolated from mouse liver microsomes]. AB - Two cytochrome P-448 fractions, B1 and B2, were isolated from liver microsomes of 3,4-benzpyrene-induced inbred C57Bl/6 mice, using chromatography on octyl Sepharose CL-4B and on Whatman 52E. During subsequent chromatography on hydroxylapatite fraction B1 was separated into 2 subfractions, G1 and G2. Cytochrome fractions B1, G1 and G2 have similar "peptide maps" differing from that of fraction B2. Cytochrome fraction B1 is immunologically identical to G2, partly to fraction B2 but is distinct from fraction G1. Fraction G2 is identified as the form of cytochrome P-448 catalyzing the hydroxylation of 3,4-benzpyrene and 7-ethoxyresorufin and existing in a low spin form. Cytochrome fraction G1 is apparently identical to the form P3-450. Fraction B2 was not yet described in current literature, since cytochrome P-448 (Mr = 53,000 Da) was identified only after the induction of mice with 3,4-benzpyrene but not with other inducers, e.g., polycyclic aromatic hydrocarbons. PMID- 3105606 TI - Membrane transport of sugar donors to the glycosylation sites. AB - The assembly of N-linked glycoproteins in eukaryotic cells begins with the segregation of these molecules within the lumen of intracellular vesicles. Since the sugar nucleotides are cytoplasmic molecules, translocation of the sugar moiety across the membrane appears as a crucial event in the glycoprotein synthesis. This N-glycosylation process occurs in two different cytological sites: in the rough endoplasmic reticulum, the stepwise synthesis of a large lipid-linked oligosaccharide takes place, as well as its transfer to protein; then after trimming the immature glycoprotein is further elongated in the Golgi apparatus. In this paper, a brief review will be given of the present knowledge on the sugar donor transport across the membrane barrier to the glycosylation site. Based upon the transmembrane orientation of oligosaccharide lipid intermediates and on the localization of the glycosyltransferase active sites, the different processes required to translocate the sugar moieties during the preassembly of the dolichyl-pyrophosphate-oligosaccharides will be examined. Combining the different results, obtained in several laboratories, it is suggested that the Man5-GlcNAc2-lipid is synthesized on the cytoplasmic side directly from the sugar-nucleotides and then translocated to the lumenal face where the Glc3-Man9-GlcNAc2-lipid is completed using Man-P-Dol and Glc-P-Dol as transmembrane carriers of these sugars. Concerning the elongation process leading to assembly of the antennae of N-acetyllactosamine type oligosaccharides, specific carriers for sugar nucleotides have been described as Golgi markers. Several authors have characterized such carriers for UDP-Gal, GDP-Fuc, CMP-NeuAc, UDP-GlcNAc and UDP-Glc using microsomal vesicles and similar results have been obtained in our laboratory using plasma membrane permeabilized cells. This carrier-mediated process leads to the formation of an intralumenal pool whose biological significance will be discussed. The translocation process of sugar donors occurring in the rough endoplasmic reticulum via lipid intermediates as well as in the Golgi apparatus via specific carriers would represent a regulation step based on the availability of the substrates for the glycosylation. PMID- 3105608 TI - [Possible role of the macromolecular environment in enzyme functioning in the cell. Interaction of E. coli beta-galactosidase with endogenous polycationic proteins and kinetic parameters of the enzyme in situ]. AB - The effect of endogenous protein polycations on the kinetic properties of beta galactosidase was studied. The dependence of kinetic properties of the enzyme (Km and V) in situ at the growth stage of microbial cultures was demonstrated. The observed phenomenon may be explained by the enzyme interaction with endogenous polycations. This interaction is of limited specificity, since it involves different types of biomolecules which display similar polyelectrolyte properties. PMID- 3105609 TI - Measurement of carbon dioxide production rate in sick ventilated premature infants. AB - A new method is described for measuring the rate of carbon dioxide production, and hence for estimating energy expenditure, in preterm infants receiving assisted ventilation. In a validation study, the mean error in carbon dioxide measurement was 1.9%. Measurements were made, over a 45-min period, on 11 sick, ventilated subjects and carbon dioxide production rate was 5.2 +/- 0.7 (SD) ml/min X kg body weight. We suggest that continuous monitoring of carbon dioxide output will contribute to the clinical assessment of the effects of different ventilator settings on pulmonary gas exchange and that estimated values for energy expenditure will be of value in nutritional studies on sick ventilated infants. PMID- 3105611 TI - Urinary levels of estrone sulfate and 11-ketotetranor prostaglandin F metabolite in pregnant guinea pigs given Clophen A50 (polychlorinated biphenyls). AB - The urinary levels of estrone sulfate and 11-ketotetranor prostaglandin F metabolite (11-ketotetranor PGF metabolite) during gestation in guinea pigs were measured by radioimmunoassays. Vehicle and Clophen A50 (polychlorinated biphenyls)-treated animals were compared. Gestation was arbitrarily divided into four periods, and the mean hormone levels during each period were compared between the two treatment groups. The Clophen A50 treatment (100 mg total, during Days 16-60), which causes fetal death, was correlated to significantly higher levels of estrone sulfate (p less than 0.05) and 11-ketotetranor PGF metabolite (p less than 0.01) during Days 47-60 (Period IV) of gestation. PMID- 3105610 TI - Effects of a potent antagonist to gonadotropin-releasing hormone on male rats: luteinizing hormone is suppressed more than follicle-stimulating hormone. AB - Previous work with female rats showed that serum levels of follicle-stimulating hormone (FSH) are suppressed by gonadotropin-releasing hormone (GnRH) antagonists less than are levels of serum luteinizing hormone (LH), suggesting a lesser dependency of FSH on GnRH stimulation. The differential regulation of LH and FSH is known to have some aspects that are sexually asymmetrical, and it was of interest to see if males also show differential gonadotropin suppressibility after injection of an antagonist to GnRH. Male rats were prepared for serial sampling 4 wk after castration. After a blood sample was removed at Time Zero, [Ac-3-Pro1, pF-D-Phe2, -D-Trp3,6]-GnRH (Antag) was injected subcutaneously in oil; doses were 0, 4, 20, 100, 500, and 2500 micrograms. Blood was sampled at 2, 5, 12, 24 and 36 h postinjection. All doses above 4 micrograms had lowered LH levels by 2 h, and LH remained suppressed for 12 to 24 h at the three higher doses. By contrast, serum FSH was unaffected by any dose at 5 h, and was only marginally suppressed by the highest doses thereafter. As in females, therefore, FSH secretion in male rats appears not to be as dependent on GnRH as is LH secretion. PMID- 3105612 TI - Effects of hyperprolactinemia on the control of luteinizing hormone and follicle stimulating hormone secretion in the male rat. AB - Experiments were conducted to determine the effects of acute hyperprolactinemia (hyperPRL) on the control of luteinizing hormone and follicle-stimulating hormone secretion in male rats. Exposure to elevated levels of prolactin from the time of castration (1 mg ovine prolactin 2 X daily) greatly attenuated the post castration rise in LH observed 3 days after castration. By 7 days after castration, LH concentrations in the prolactin-treated animals approached the levels observed in control animals. HyperPRL had no effect on the postcastration rise in FSH. Pituitary responsiveness to gonadotropin hormone-releasing hormone (GnRH), as assessed by LH responses to an i.v. bolus of 25 ng GnRH, was only minimally effected by hperPRL at 3 and 7 days postcastration. LH responses were similar at all time points after GnRH in control and prolactin-treated animals, except for the peak LH responses, which were significantly smaller in the prolactin-treated animals. The effects of hyperPRL were examined further by exposing hemipituitaries in vitro from male rats to 6-min pulses of GnRH (5 ng/ml) every 30 min for 4 h. HyperPRL had no effect on basal LH release in vitro, on GnRH-stimulated LH release, or on pituitary LH concentrations in hemipituitaries from animals that were intact, 3 days postcastration, or 7 days postcastration. However, net GnRH-stimulated release of FSH was significantly higher by pituitaries from hyperprolactinemic, castrated males. To assess indirectly the effects of hyperPRL on GnRH release, males were subjected to electrical stimulation of the arcuate nucleus/median eminence (ARC/ME) 3 days postcastration. The presence of elevated levels of prolactin not only suppressed basal LH secretion but reduced the LH responses to electrical stimulation by 50% when compared to the LH responses in control castrated males. These results suggest that acute hyperPRL suppresses LH secretion but not FSH secretion. Although pituitary responsiveness is somewhat attenuated in hyperprolactinemic males, as assessed in vivo, it is normal when pituitaries are exposed to adequate amounts of GnRH in vitro. Thus, the effects of hyperPRL on pituitary responsiveness appear to be minimal, especially if the pituitary is exposed to an adequate GnRH stimulus. The suppression of basal LH secretion in vivo most likely reflects inadequate endogenous GnRH secretion. The greatly reduced LH responses after electrical stimulation in hyperprolactinemic males exposed to prolactin suggest further that hyperPRL suppresses GnRH secretion. PMID- 3105613 TI - A serum-free defined culture system which maintains follicle-stimulating hormone responsiveness and differentiation of porcine granulosa cells. AB - A serum-free defined culture system has been developed that maintains follicle stimulating hormone (FSH)-dependent differentiation of porcine granulosa cells from small follicles for up to six days in culture. Confluent monolayers of epithelioid cells were established after culture on fibronectin-coated culture dishes (FBN, 2 micrograms/cm2) in nutrient medium supplemented with human low density lipoprotein (LDL, 10 micrograms/ml), insulin (I, 1 microgram/ml), and thrombin (TH, 1 NIH U/ml). Each of these factors was necessary to maintain the epithelioid morphology of the monolayers that attained 70% of the protein content and 71% of the cell number of replicate cultures maintained in nutrient medium supplemented with 10% fetal calf serum and insulin. Addition of FSH to the FBN/LDL/I/TH-supplemented cultures resulted in dose-dependent increases in progesterone secretion and [125I]-iodo-human chorionic gonadotropin (hCG) binding comparable to those obtained in the cultures containing serum. These results indicate that the attachment, epithelioid morphology, and differentiated function of porcine granulosa cells (GCs) can be maintained in defined culture conditions. This culture system will facilitate study of the effects of growth promoters and differentiative agents on GC function in the absence of poorly defined serum supplements. PMID- 3105614 TI - Relationships between luteinizing hormone, follicle-stimulating hormone and prolactin secretion and ovarian follicular development in the weaned sow. AB - Folliculogenesis was studied by assessing development of the largest 10 follicles obtained from 10 sows 48 h after weaning and by analyzing changes in plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) for 24 h before weaning until 48 h after weaning. Follicular diameter, follicular fluid volume, and concentrations of estradiol and testosterone and granulosa cell numbers were determined in all follicles, and 125I-hCG binding to theca and granulosa and maximal aromatase activity in vitro was determined in five follicles/sow. Overall, a significant rise in LH, but not in FSH, occurred at weaning, although in individual sows an increase in LH was not necessarily related to subsequent estrogenic activity of follicles. In 9/10 sows, PRL fell precipitously after weaning. In lactation, LH was negatively, and after weaning, positively, correlated with FSH and PRL. Marked variability in follicular development existed within and between sows. Overall, most follicular characteristics were positively correlated to follicular diameter; however, in larger follicles the number of granulosa cells was variable and unrelated to estrogenic activity, which--together with theca and granulosa binding of hCG- increased abruptly at particular stages of follicular development. Differences in maturation of similarly sized follicles from different sows were related to estrogenic activity of the dominant follicles but not to consistent differences in LH, FSH or PRL secretion. Both the dynamics and the control of folliculogenesis in the sow, therefore, appear to be complex. PMID- 3105615 TI - Linear rank tests for interval-censored data with application to PCB levels in adipose tissue of transformer repair workers. AB - Linear rank statistics are described for testing for differences between groups when the data are interval-censored. The statistics are closely related to those described by Prentice (1978, Biometrika 65, 167-179) for right-censored data. Problems in calculating the statistics are discussed and several approaches to computation including estimation of the efficient rank scores are described. Results from a small simulation study are presented. The methods are applied to data from a study relating tissue levels of PCBs to occupational exposure. PMID- 3105616 TI - [Anticonvulsive effect of superoxide dismutase]. AB - The influence of superoxide dismutase (SOD) on the development of focal epileptic activity (EpA) in the rat brain cortex has been investigated. Intraperitoneal administration of SOD to rats (1 mg/kg) 30 minutes before penicillin application to the sensorimotor cortex led to marked relaxation of EpA and a decrease in the concentration of lipid peroxidation (LPO) products in EpA focus. The results corroborate our earlier assumption on an important pathogenetic role of LPO disturbances in epileptogenesis and make reasonable the combination of the traditional anticonvulsive therapy with the agents activating the oxidative system. PMID- 3105617 TI - [The role of endogenous regulators in the compensatory process after salivary gland resection]. AB - The ways of penetration of submandibular salivary degeneration products into the blood after partial gland resection have been studied on 97 rats. Using isoenzyme LDH spectrum of the blood, as well as of gland and regional lymph node tissue, the acid-base balance values and morphological data, it has been shown that degeneration products of salivary glands penetrate into the general blood flow through regional lymph nodes, where they are partly modified. The true changes in LDH spectrum can be already registered half an hour after the injury of the gland. The influence of the degeneration products of gland tissue on the initiation of the compensation processes in cellular hyperplasia is discussed. PMID- 3105618 TI - Immunoradiometric quantitation of tissue plasminogen activator-related antigen in human plasma: crypticity phenomenon and relationship to plasma fibrinolysis. AB - A two-site immunoradiometric assay for tissue plasminogen activator (tPA) antigen has been developed using immunoaffinity purified antibody. Various treatments enhanced the detection of tPA antigen in the plasma samples. Maximum detection was obtained by acidification of plasma to pH 4.8 to 6.5 or addition of 0.5 mol/L of L-lysine or L-arginine. Acidification or addition of lysine to plasma is also required for maximum immunoadsorption of plasma tPA antigen on anti-tPA-Ig sepharose. These results indicate that plasma tPA antigen is partially cryptic to antibody in untreated plasma. The plasma tPA antigen isolated by immunoadsorption of either untreated plasma or acidified plasma on anti-tPA-Ig-sepharose consists mainly of a 100-kd plasminogen activator species as determined by fibrin-agar zymography. The 100-kd activity is possibly a tPA:inhibitor complex. A standardized sample preparation method was conveniently adopted by mixing 3 vol of plasma and 1 vol of 2 mol/L of L-lysine for the assay. Reconstitution and recovery studies showed that the method is specific and permits full detection of both free tPA and tPA:inhibitor complex. The validity of the assay is further supported by the finding that the spontaneous plasma fibrinolysis previously demonstrated to be dependent on plasma tPA antigen is correlated with tPA antigen content. Using the standardized assay, we found that tPA antigen concentrations in 16 blood bank plasmas are equivalent to 3.7 to 20 ng of 60 kd tPA/mL. In all the plasma tested, more than half of the antigen is undetected unless the plasma is treated as described above. PMID- 3105619 TI - Initiation and regulation of fibrinolysis in human plasma at the plasminogen activator level. AB - The initiation and regulation of fibrinolysis has been studied by reconstitution of fibrinolytic activity in human plasma in vitro. Depletion of tissue plasminogen activator (tPA) antigen by immunoadsorption of human plasma with anti tPA Ig Sepharose 4B leads to total loss of spontaneous fibrinolytic activity determined by lysis of a thrombin-induced clot. Addition of physiological concentrations of purified tPA to tPA-depleted plasma restores fibrinolytic activity as a function of the length of time between tPA addition and clotting. Addition of free tPA to tPA-depleted plasma followed by immediate clotting results in a high rate of fibrinolysis. In contrast, when free tPA is allowed to incubate in plasma for 10 to 60 minutes prior to clot formation, the fibrinolytic activity of tPA is gradually lost. The loss of tPA-induced fibrinolytic activity in unclotted plasma is accompanied by decreased partitioning of tPA antigen into fibrin after clotting and is kinetically correlated with the formation of a 100 kilodalton (kDa) tPA complex as demonstrated by SDS-gel electrophoresis and fibrin-agar zymography. These results suggest that free tPA is susceptible to complexation by the plasma inhibitor in the absence of a clot. Fibrin formation renders tPA relatively inaccessible to inhibition. The tPA antigen isolated from stored plasma consists mainly of 100 kDa activity in SDS-gel electrophoresis and zymography, indicating that the tPA complex is resistant to dissociation by SDS. Upon rezymography of the sliced gel, only a 60 kDa tPA activity is found, suggesting that the activity at 100 kDa is at least partly due to free tPA dissociated from the complex during the first zymography. Conversion of tPA complex to enzymatically active free tPA also occurs with brief SDS exposure followed by incubation in the presence of excess Triton X-100 or by hydroxylamine treatment. These results reconcile the apparent discrepancy of the 100 kDA inhibitor-tPA complex manifesting plasminogen activation activity during zymography. The plasma tPA-inhibitor complex is precipitated strongly by antisera against plasminogen activator inhibitors (PAIs) of human Hep G2 hepatoma and HT 1080 fibrosarcoma cells and weakly by antiserum against bovine aortic endothelial cell PAI but not by antiserum against a placental PAI (PAI-2) suggesting that the plasma inhibitor is immunologically related to Hep G2, HT-1080 and possibly endothedial cell PAIs. Based on the above findings, a simple model for the initiation and regulation of plasma fibrinolysis at the PA level has been formulated. PMID- 3105621 TI - Expression of the M-CSF (CSF-1) gene by human monocytes. AB - Monocyte colony-stimulating factor (M-CSF, CSF-1) is a macrophage lineage specific growth factor. Northern blot analysis using a human M-CSF cDNA probe and a specific bioassay for human M-CSF were used to investigate the cellular sources of M-CSF. Expression of the M-CSF gene was induced in blood mononuclear cells stimulated by phorbol myristate acetate (PMA) or gamma-interferon. When mononuclear cells were fractionated into highly purified populations of T cells and monocytes, M-CSF transcripts were detected predominantly in monocytes. Further, monocytes stimulated with PMA released an M-CSF-like activity. These results demonstrate that M-CSF can be produced by activated cells of the macrophage lineage. PMID- 3105620 TI - Receptor-specific inhibition of bone marrow erythropoiesis by recombinant DNA derived interleukin-2. AB - Interleukin-2 (IL-2) induces differential secretion of lymphokines by IL-2 receptor (IL-2R)-positive and IL-2R-negative T cells. We studied T cell IL-2R specific modulation of adult bone marrow erythropoiesis by recombinant IL-2 (rIL 2). I3-2R were induced by CD3 T cell surface determinant-triggering and analyzed by cytofluorography. Bone marrow monocyte and T cell-depleted (NAB-T) target cells were assessed for early erythroid progenitor expression (BFU-E) in the presence of 0 to 10(3) U/mL of rIL-2, rIL-2 had no significant effect on BFU-E expression in the absence of T cells or in the presence of IL-2R-negative T cells. rIL-2 caused a dose-dependent inhibition (75% to 90%) of BFU-E in the presence of autologous IL-2R-positive T cells. The addition of anti-IL2-receptor antibody to cultures containing rIL-2 plus IL-2R-positive T cells entirely abrogated rIL-2-mediated inhibition of BFU-E. In the presence of rIL-2 (10(2) U/mL) production of interferon gamma (IF-gamma) by adult marrow CD3-triggered IL 2R-positive T cells was increased 37- to 125-fold compared to IL-2R-negative T cells. rIF-gamma caused a dose-dependent (88% +/- 17% at 10(3) U/mL) inhibition of adult BFU-E in the presence of CD3-triggered autologous T cells. rIL2-mediated inhibition of adult BFU-E in the presence of IL-2R-positive T cells was partially abrogated (52% +/- 16%) following addition of monospecific IF-gamma antibody. These results demonstrate (a) rIL-2 modulation of adult marrow erythropoiesis is selectively dependent upon both the presence or absence of autologous T cells and the IL-2R status of these T cells; and (b) rIL-2-induced inhibition of adult marrow erythropoiesis is mediated in part by release of IF-gamma from IL-2R positive T cells. PMID- 3105622 TI - Type IIA von Willebrand disease with apparent recessive inheritance. AB - Type IIA von Willebrand's Disease (vWD) is the most common type II variant, and all reported cases (56 individuals in 26 families) have had autosomal dominant inheritance. An eight-year-old female with an increased bleeding tendency since infancy was found to have laboratory values typical of type IIA vWD, but her parents and siblings were asymptomatic. With the exception of uniformly decreased levels of ristocetin cofactor in relation to von Willebrand factor antigen, the results of family studies were normal including the presence of large multimeric forms of von Willebrand factor antigen. These findings are consistent with the propositus having the homozygous state of an autosomal recessive trait. Desmopressin infusion in the propositus was followed by a significant increase of factor VIII coagulant and von Willebrand factor antigen but a limited change in ristocetin cofactor with no development of large multimers. PMID- 3105623 TI - Cytosolic free calcium levels in sickle red blood cells. AB - In this study, we used a recently developed nuclear magnetic resonance (NMR) technique to measure ionized calcium in sickle erythrocytes. The NMR technique, which involves 19F NMR studies of a fluorinated calcium chelator quinMF, [2-(2 amino-4-methyl-5-fluorophenoxy)methyl-8-aminoquinoline-N,N,N',N'- tetraacetic acid] provides a novel approach to the study of ionized calcium in erythrocytes since the presence of hemoglobin precludes the use of fluorescent calcium indicators. The mean value for ionized calcium in oxygenated sickle erythrocytes was 18 +/- 2 nmol/L (SE). Experiments with normal RBCs gave a mean value of 21 +/ 2 nmol/L (SE). After 1 hour of deoxygenation, mean values for ionized calcium in sickle erythrocytes did not increase as compared with values obtained under oxygen. To investigate whether deoxygenation stimulated endocytosis, sickle erythrocytes were deoxygenated for 1 hour in the presence of impermeant FBAPTA (1,2 bis-(2-amino-5-fluorophenoxy) ethane N,N,N',N'-tetraacetic acid). Cells were then separated from the extracellular medium and assayed for the presence of FBAPTA; they had incorporated significant quantities of the extracellular FBAPTA. This incorporation was not observed with normal erythrocytes. These data are consistent with at least a portion of the elevation in total cell calcium in sickle erythrocytes arising as a consequence of an endocytotic process in which extracellular calcium ions are incorporated into vesicles. Additional experiments show that these intracellular vesicles accumulate Ca2+ on further deoxygenation, consistent with a transient increase in ionized cell calcium. These studies represent the first use of NMR spectroscopy to evaluate endocytotic processes. PMID- 3105624 TI - von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively. AB - Large multimers of von Willebrand factor (vWf) are released from the Weibel Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix. PMID- 3105625 TI - Expression of c-fos, c-myb, and c-myc in human monocytes: correlation with monocytic differentiation. AB - Terminal differentiation of human monocytic leukemia cells (THP-1 cells) was associated with the induction of c-fos, the down regulation of c-myb, and no significant change in the level of c-myc expression. Gamma interferon, which resulted in a slight decrease in c-myb but no change in c-fos or c-myc expression, had a transient antiproliferative effect without a morphological or functional differentiation of THP-1 cells. Resting human peripheral blood monocytes have a high c-fos, a low c-myc, and no detectable c-myb expression. These findings suggest that a switch in c-fos/c-myb expression is associated with the terminal differentiation of cells of the monocytic lineage. PMID- 3105626 TI - Immune status of Greek patients with beta-thalassemia major negative for anti HIV. AB - Patients with thalassemia who receive multiple blood transfusions are at risk for the acquired immunodeficiency syndrome. Peripheral blood lymphocyte subpopulations were studied in 22 multitransfused thalassemic patients; 10 patients were without splenectomy and 12 were studied after splenectomy. Both groups were negative for anti-HIV. Four additional patients who were found positive for anti-HIV and ten healthy controls were also included in this study. Patients without splenectomy compared to controls and to patients after splenectomy showed a significant decrease of both percentage (p less than 0.001) and absolute numbers (p less than 0.001) of Leu-7+ cells without significant abnormalities of T4/T8 ratio (1.56 +/- 0.4). Patients after splenectomy compared to controls and to patients without splenectomy showed a significant increase of the absolute numbers of lymphocytes and lymphocytes subsets T11+, T3+, T4+, T8+ and SmIg+ cells. In the seropositive patients for HIV only a significant increase of the absolute number of T8+ cells was observed while the T4/T8 ratio was 1.24 +/- 0.73. The decrease in the percentage of Leu-7+ cells in patients without splenectomy correlated inversely to the total amount of blood transfused. In conclusion patients with thalassemia had normal T4/T8 ratio and did not show the abnormal immunologic profile that has been reported in haemophiliacs. PMID- 3105627 TI - Increased factor VIII/vWf levels in patients with reduced platelet number. AB - Factor VIII/von Willebrand factor (VIII/vWf) related properties were studied in twenty six patients with thrombocytopenia. Fifteen patients were affected by idiopathic thrombocytopenic purpura (ITP) and 11 patients by thrombocytopenia of a different nature or non-ITP (n-ITP). All patients showed an enhancement of platelet associated IgG (PAIgG). A significant increase of factor VIII ristocetin cofactor (VIII R: RCoF) and factor VIII related antigen (VIII R:Ag) was found in ITP patients while normal values were observed for factor VIII coagulant (VIII:C). All factor VIII/vWf components, on the contrary, were increased in n ITP group with a prevalence of VIII R:RCoF as observed in ITP group even though with lower mean values. Multimeric analysis of VIII/vWf demonstrated a higher concentration of all multimeric components, with major representation of higher molecular weight multimers (HMWM) in patients of both groups. Two patients were studied before and after improvement in platelet count. A decrease of vWf related properties (VIII R:RCoF and VIII R:Ag) concomitant with the increase in platelet count was found. In n-ITP patients a statistical correlation between VIII R:RCoF and PAIgG was also observed while no correlation was found between other factor VIII/vWf components and PAIgG both in ITP and n-ITP patients. PMID- 3105628 TI - [Current role of chemotherapy in the treatment of adenocarcinomas of the endometrium]. PMID- 3105629 TI - Comparison of the promutagenic activity of liver homogenates from fish and rat in the Ames test. PMID- 3105630 TI - [Studies on the chemical analysis of mycotoxin (XIII). Determination of aflatoxin B1 in edible oil]. PMID- 3105631 TI - Intravesical mitomycin C for the treatment of recurrent superficial bladder tumours. AB - Forty-three patients with recurrent multiple superficial bladder tumours (Tis, Ta and Tl) were treated with Mitomycin C 20 mg in 20 ml water intravesically weekly for 8 to 12 weeks, and monthly instillations were continued for 5 to 6 months. Residual tumour was resected at 12 weeks, at which time 40 patients (93%) showed a response to treatment. A complete response was seen in 24 (56%) and 16 (37%) showed a partial response. After a follow-up of 12 to 48 months (median 19), 19 of 33 evaluable patients (58%) have shown tumour recurrence. Invasive tumour has developed in seven (17%) and transitional cell tumours of the ureter in two of those patients who showed an initial response to treatment. PMID- 3105632 TI - Parenteral nutrition in the surgical patient. PMID- 3105633 TI - The consultant's role in continuing medical education of general practitioners: the case of rheumatology. AB - Consultant rheumatologists were surveyed by questionnaire about their contribution to the continuing education of general practitioners, and 84% (203/243) replied. Altogether 157 respondents had participated in some form of teaching, 147 in collective teaching sessions such as lectures and 99 in the teaching of small groups. Arthritis comprised 44% of the rheumatological topics taught; there was a noticeable lack of teaching on problems commonly encountered in general practice, such as soft tissue rheumatism and injury and back pain, and on clinical skills including examination and injection of joints. Eighty eight respondents made comments and suggestions. The favoured educational strategies were small group teaching, apprenticeship schemes, and interchange between general practitioners and consultants about shared cases. This contrasts with what was typically done--namely, formal lectures on rheumatoid arthritis in postgraduate medical centres. These findings raise questions about the continuing education of consultants themselves as well as about the consultants' role in teaching others. PMID- 3105634 TI - Severe eczema of the hands due to an orthopaedic plate made of Vitallium. PMID- 3105635 TI - Reflections on death in childhood. PMID- 3105636 TI - Association between liberalization of Scotland's liquor licensing laws and admissions for self poisoning. PMID- 3105637 TI - Long live health promotion. PMID- 3105638 TI - Human papillomavirus infection of the uterine cervix of women without cytological signs of neoplasia. PMID- 3105639 TI - Childhood respiratory infection and adult chronic bronchitis in England and Wales. PMID- 3105640 TI - Dignity in hospital. PMID- 3105641 TI - Asthma and climatic conditions: experiences from Hong Kong. PMID- 3105642 TI - Hip fractures in healthy patients. PMID- 3105643 TI - Effect of aspirin on pruritus. PMID- 3105644 TI - Carcinoma in situ of the contralateral testis. PMID- 3105645 TI - Infectious diseases physicians and microbiologists. PMID- 3105646 TI - Paradoxical gas embolism in a scuba diver with an atrial septal defect. PMID- 3105647 TI - Acquired cystic disease of the kidney. PMID- 3105648 TI - Heat inactivation of specimens--AIDS. PMID- 3105649 TI - Primary pulmonary hypertension. PMID- 3105650 TI - Corticosteroids and bone mass in asthma. PMID- 3105651 TI - Neurological and neurosurgical approaches in the management of malignant brain tumours. PMID- 3105652 TI - Cost of anaesthetic drugs and clinical budgeting. PMID- 3105653 TI - Pelvic pain in women. PMID- 3105654 TI - Alfacalcidol and hypercalcaemia. PMID- 3105655 TI - Endoscopic removal of a pharmacobezoar of slow release theophylline. PMID- 3105656 TI - Fluorouracil and angina. PMID- 3105657 TI - Hypothyroidism after treatment with ketoconazole. PMID- 3105658 TI - Psoriasis, cyclosporin A, and AIDS. PMID- 3105659 TI - Day surgery: does it add to or replace inpatient surgery? PMID- 3105660 TI - The unremitting burden on carers. PMID- 3105661 TI - The increase in molluscum contagiosum. PMID- 3105662 TI - French lessons on surveillance of communicable diseases. PMID- 3105664 TI - Early onset pre-eclampsia: recognition of underlying renal disease. AB - A follow up study of 84 patients with early onset pre-eclampsia (before 37 weeks' gestation) showed a high prevalence of underlying renal disease. Renal abnormalities were found in 33 of the 49 primiparas (67%) and in 22 of the 35 multiparas (63%). Two thirds of the multiparas with pre-eclampsia before 37 weeks with a diagnosis of either essential hypertension or renal disease had recurrent pre-eclampsia. Maternal morbidity and fetal mortality were greater in the group with early onset pre-eclampsia than in a group with late onset disease. Idiopathic pre-eclampsia occurred in 10% of primiparas in the early onset group, whereas it was the main condition in over three quarters of primiparas in the late onset group. A presumptive diagnosis of idiopathic pre-eclampsia is likely to be correct only in primiparas who develop the disease after 37 weeks of pregnancy; in all other cases careful search will almost certainly detect an underlying abnormality, predominantly renal. PMID- 3105663 TI - Depression after stroke. PMID- 3105665 TI - Life threatening sickle chest syndrome treated with extracorporeal membrane oxygenation. AB - A young West Indian woman with established sickle cell disease developed a severe episode of sickle chest syndrome. Conventional treatment including exchange transfusions and mechanical ventilation was to no avail, and an infusion of epoprostenol also failed to halt her worsening condition. When her arterial oxygen tension (PaO2) had fallen to 6.5 kPa (49 mm Hg) extracorporeal membrane oxygenation was instituted. Within two days her PaO2 was greatly improved (maximum 11.6 kPa; 87 mmHg), and by the sixth day pulmonary vascular resistance was reduced and angiography showed reperfusion of many vessels. The patient recovered and six months later showed a transfer factor close to the predicted range and normal spirometric values. Extracorporeal membrane oxygenation should be considered for severe sickle chest syndrome when conventional methods of artificial ventilation fail. PMID- 3105666 TI - Inoperable aortic stenosis in the elderly: benefit from percutaneous transluminal valvuloplasty. AB - Eight patients with severe symptomatic calcific aortic stenosis were considered to be unsuitable for valve replacement. Four were admitted with pulmonary oedema and three in cardiogenic shock and one had angina at rest. With the use of echocardiographic and radiographic guidance percutaneous transluminal aortic valvuloplasty was carried out. Aortic gradients were reduced by an average of 40%. All four patients who presented with cardiac failure improved immediately and remained well six months later. The patient with angina was symptom free at nine months. Two of the three patients who presented in cardiogenic shock improved immediately and were well nine and three months later. The other patient died four hours after the procedure. Doppler echocardiographic studies showed a slight initial increase in aortic incompetence, but this did not worsen and valvar gradients remained improved three and six months later. Percutaneous valvuloplasty of the aortic valve is an effective therapeutic option in patients with severe calcific aortic stenosis who are unfit for surgery. Its role as an alternative to surgery has not been considered and should be investigated in a controlled clinical trial. PMID- 3105668 TI - What is a good GP? PMID- 3105667 TI - Unemployment and mortality: comparison of the 1971 and 1981 longitudinal study census samples. AB - Mortality in the period 1981-3 among men in the Office of Population Censuses and Surveys longitudinal study who were seeking work in 1981 was examined to investigate whether the finding of a high mortality rate among a comparable group of men who were followed up from the 1971 Census was repeated despite appreciable changes in the size and structure of the labour force over the intervening years. The pattern of mortality shortly after both censuses suggests that sick unemployed men were not categorised as seeking work, and it is concluded that for both samples the mortality of those who were reported to be seeking work was raised for reasons other than initial poor health. Other findings from the two censuses are also broadly similar. If confirmed after longer follow up this will add considerably to the evidence of the adverse health consequences of unemployment. PMID- 3105669 TI - Attitudes to prescribing iron supplements in general practice. AB - In response to a postal questionnaire general practitioners in the Southampton and New Forest area indicated a considerable understanding of the principles of iron prescribing and use of laboratory tests to determine iron deficiency. Many respondents, however, chose slow release and compound iron preparations as first treatments for iron deficiency. The role of parenteral iron appeared to be poorly understood. The use of and response to laboratory investigations for iron deficiency were generally appropriate, but many practitioners probably do not check for a response to oral iron sufficiently early during treatment or stop prescribing supplements before iron stores have been replenished. There is scope for further education in the biology and management of iron deficiency in general practice. PMID- 3105670 TI - The Liverpool urban obstetric flying squad: changing patterns of practice 1965 84. AB - Obstetric flying squads operate from most maternity units in the United Kingdom. The 20 years from 1965 to 1984 saw 860 calls being made to the obstetric flying squad in the Liverpool urban area, with striking changes occurring in both the number of calls made and the reasons for making the calls. Management of the problems encountered has now become almost exclusively conservative, with such procedures as blood transfusion and general anaesthesia being virtually eliminated from practice. PMID- 3105671 TI - Do adhesions cause pain? PMID- 3105672 TI - Wellcome developments in tropical medicine. PMID- 3105673 TI - Through the carpal tunnel. PMID- 3105674 TI - Retinal detachment. PMID- 3105676 TI - Called to account. PMID- 3105675 TI - The heritability of congenital heart disease. PMID- 3105677 TI - Social skills training. PMID- 3105678 TI - A poor start for the Health Education Authority. PMID- 3105680 TI - Systolic and diastolic blood pressures as predictors of coronary heart disease in middle aged Norwegian men. AB - Systolic and diastolic blood pressures were compared as predictors of mortality from coronary heart disease in Norwegian men aged 35-49. A total of 39,207 men were followed up for an average of 8.9 years; 385 died of coronary heart disease. Diastolic blood pressure seemed to be the better predictor, the difference being most pronounced in the age group 35-39. At this age 26% more deaths from coronary heart disease were found in the upper quintile of diastolic blood pressure compared with the upper quintile of systolic blood pressure. At ages 45-49 there were almost the same numbers of deaths from coronary heart disease in the upper quintiles of systolic and diastolic pressures. These findings suggest that the relative predictive strength of systolic and diastolic blood pressure may be dependent on age. Furthermore, for very obese men the association between blood pressure and death from coronary heart disease is much weaker. PMID- 3105679 TI - Partial splenic embolisation for hypersplenism of thalassaemia major: five year follow up. AB - Six patients with thalassaemia major were treated by partial splenic embolisation as an alternative to splenectomy and followed up for five years. Results were compared with those in a matched control group of seven patients treated by splenectomy. All patients treated by partial splenic embolisation showed a reduction in blood transfusion requirements comparable with those in the controls and which remained unchanged over the five years. Serious infections that commonly occur in patients splenectomised for thalassaemia did not occur after embolisation, presumably owing to preservation of some immune function by the splenic remnant. By contrast with the change in platelet counts seen after splenectomy, platelet counts remained normal after partial splenic embolisation, so reducing the risk of thromboses. On the other hand, pre-existing leucopenia and thrombocytopenia were corrected after embolisation. It is concluded that partial splenic embolisation provides an alternative to splenectomy for thalassaemia major and is equally effective and much safer. PMID- 3105681 TI - Pinch skin grafting or porcine dermis in venous ulcers: a randomised clinical trial. AB - Chronic venous ulcers are common, and even with effective compression or elevation large ulcers may take months to heal. Pinch skin grafting may allow healing from epithelial islands throughout the surface area of the ulcer, and a prospective randomised trial was therefore conducted comparing this treatment with porcine dermis dressings. Most patients were treated as outpatients, 25 ulcers being randomised to treatment with pinch skin grafts and 28 to treatment with porcine dermis. Though the groups were well matched, the mean healing rate in the first week was 15 cm2 for pinch skin grafts compared with 3.5 cm2 with porcine dermis (p less than 0.02). By life table analysis 64% of ulcers treated by pinch grafts were healed at six weeks and 74% by 12 weeks compared with 29% and 46% of ulcers, respectively, treated with porcine dermis dressings (chi2 = 4.1; p less than 0.05). All ulcers that failed to heal within 12 weeks included an area posterior to the medial malleolus, where local compression may have been inadequate. Pinch skin grafting improves the rate of healing in large venous ulcers and is a simple technique that may be performed as an outpatient procedure under local anaesthesia. PMID- 3105682 TI - Increased bacterial antibody titres and IgA deficiency in epileptic patients. PMID- 3105683 TI - Coagulation studies in cases of intrauterine death: overkill? PMID- 3105684 TI - Primary nocturnal enuresis in children with vesicoureteric reflux. PMID- 3105686 TI - Tinel's sign and the carpal tunnel syndrome. PMID- 3105685 TI - Extranodal lymphoma in a haemophiliac negative for antibody to HIV. PMID- 3105687 TI - What to do when you don't trust your doctor. PMID- 3105688 TI - Acute colitis in a district general hospital. AB - A review of all patients who had been admitted to hospital with acute ulcerative colitis in one health district between 1975 and 1984 showed that 96 had required 114 admissions with acute colitis: 42% (40) were admitted during their first attack, and 20% (19) required urgent surgery. A further nine patients underwent surgery after responding initially to intensive medical treatment that did not check the attack. There were no deaths from acute colitis. Thirteen patients underwent elective surgery for ulcerative colitis, and there were no deaths. The prognosis for acute colitis in district general hospitals has improved. PMID- 3105689 TI - Impact of cuts in acute beds on services for patients. AB - The current redistribution of resources in the National Health Service will require a reduction in the number of acute beds in many district health authorities. The effect of such a reduction on services for patients was examined. Two hundred and two general medical admissions and 201 general surgical admissions to hospitals in West Lambeth District Health Authority were reviewed retrospectively. The elements considered were the severity of the patient's illness at admission, the scope for reducing the length of stay, the potential for other forms of care, and what types of patients would be denied access at different levels of reductions in the number of beds. Given the assumptions a considerable potential for maintaining levels of service with fewer beds was identified. The finding was, however, that even if all of this potential was realised the cuts in the number of beds that are planned by districts that are losing resources would force real reductions in patient services. This suggests a "trade off." To increase services in districts that are gaining resources, real unmet need may have to be created in districts that are losing resources. PMID- 3105690 TI - The baby show. PMID- 3105691 TI - ABC of 1 to 7 (revised). Recurrent headache. PMID- 3105692 TI - Eczema herpeticum: a potentially fatal disease. PMID- 3105693 TI - Dr Gee goes to the House of Lords. PMID- 3105694 TI - The elusive orthopedic senior house officer. PMID- 3105695 TI - Osteoporosis: cause and management. PMID- 3105696 TI - When a woman asks for a caesarean section. PMID- 3105697 TI - Psychiatric disorder and gynaecological symptoms in middle age women. PMID- 3105698 TI - Acyclovir and pregnancy. PMID- 3105699 TI - Oral acyclovir in acute herpes zoster. PMID- 3105700 TI - Better reporting of adverse drug reactions. PMID- 3105701 TI - Pulmonary hypertension. PMID- 3105702 TI - HIV transmitted by kissing. PMID- 3105703 TI - Early emergency care. PMID- 3105704 TI - Occult chlamydial ophthalmia in men with non-gonococcal urethritis. PMID- 3105705 TI - Changing iodine intake and the effect on thyroid disease. PMID- 3105707 TI - Drums begin to beat in the waiting list jungle. PMID- 3105706 TI - Solvent abuse and the heart. PMID- 3105709 TI - Original pack dispensing. PMID- 3105708 TI - Overuse of monitoring of blood concentrations of antiepileptic drugs. PMID- 3105711 TI - Coronary prevention in Britain: action at last? PMID- 3105710 TI - Are pesticides carcinogenic? PMID- 3105712 TI - Chronic cardiac toxicity after inhalation of 1,1,1-trichloroethane. AB - Two patients showed evidence of chronic cardiac toxicity after repeated exposure to 1,1,1-trichloroethane. In both cases there was circumstantial evidence of a deterioration after routine anaesthetic use of the related compound halothane. An adolescent boy who sniffed trichloroethane presented with multiple ventricular arrhythmias during tonsillectomy. Follow up showed mild chronic left ventricular impairment. A 54 year old man had repeated industrial exposure to trichloroethane and deteriorated from mild stable cardiac failure to end stage cardiac failure after halothane anaesthesia for herniorrhaphy. Chronic cardiac toxicity is a previously unreported feature of this type of solvent exposure. Related compounds such as halothane may have a toxic interaction after exposure to trichloroethane. PMID- 3105713 TI - Digoxin-like immunoreactive substance in patients with aneurysmal subarachnoid haemorrhage. AB - Digoxin was measured by radioimmunoassay in the plasma of 25 patients with aneurysmal subarachnoid haemorrhage who had not received digoxin treatment. After heating the plasma an endogenous substance cross reacting with antibodies to digoxin was identified in 18 cases. The presence of this substance was significantly related to the total amount of blood and to the presence of blood in the frontal interhemispheric fissure and could not be explained by hypertension or intake of water and sodium. A negative sodium balance and volume depletion occurred more often in patients who were positive for digoxin, but this relation did not reach statistical significance. It is concluded that a digoxin like natriuretic factor is released in response to a subarachnoid haemorrhage, probably as a result of hypothalamic damage. PMID- 3105714 TI - Alcohol and ischaemic heart disease in middle aged British men. AB - The relation between alcohol intake and ischaemic heart disease was examined in a large scale prospective study of middle aged men drawn from general practices in 24 British towns. After an average follow up of 6.2 years 335 of the 7729 men had experienced a myocardial infarction (fatal or non-fatal) or sudden cardiac death. No significant relation was found between reported alcohol intake and the incidence of such events. Though the group of light daily drinkers had the lowest incidence of ischaemic heart disease events, it also contained the lowest proportion of current smokers, had the lowest mean blood pressure, had the lowest mean body mass index, and contained the lowest proportion of manual workers. These characteristics are more likely to account for the apparent protective effect of alcohol against ischaemic heart disease than a direct effect of alcohol. Compared with the effects of established risk factors alcohol seems to be quite unimportant in the development of ischaemic heart disease. PMID- 3105716 TI - "Glue sniffer's" heart? PMID- 3105715 TI - Congenital rubella in babies of south Asian women in England and Wales: an excess and its causes. AB - The incidence of congenital rubella was found to be 2.3 times higher in Asian than non-Asian births in England and Wales. This was attributed in part to higher susceptibility to rubella in Asian than non-Asian women, as shown by antenatal serological data from public health laboratories in Leeds, Luton, and Manchester. Examination of the ethnic origin of pregnant women requesting laboratory testing after contact with rubella or rash and of women with laboratory confirmed rubella in pregnancy also suggested that the disease was being underdiagnosed in pregnant Asian women. Failure to prevent congenital rubella by termination of infected pregnancies may therefore contribute to the increased incidence of the syndrome in Asians. Health education programmes about the dangers of rubella in pregnancy and of the need for vaccination can readily be promoted in the Asian community through existing ethnic organisations. Protection of other ethnic minorities likely to be at similar increased risk may require a vaccination programme aimed at national elimination of rubella. PMID- 3105717 TI - Myocardial infarction and primary ventricular fibrillation after glue sniffing. PMID- 3105718 TI - Ectopic pregnancy in Finland 1967-83: a massive increase. PMID- 3105719 TI - Treatment of palindromic rheumatism with chloroquine. PMID- 3105720 TI - Indigenous strongyloidiasis in Nottingham. PMID- 3105721 TI - Infection by airborne Chlamydia trachomatis in a dentist cured with rifampicin after failures with tetracycline and doxycycline. PMID- 3105722 TI - Perforation of nasal septum due to button battery lodging in nose. PMID- 3105723 TI - How complete is a total parathyroidectomy in uraemia? PMID- 3105724 TI - Are isolated maternity units run by general practitioners dangerous? AB - A retrospective survey was carried out of women admitted in labour to an isolated maternity unit run by general practitioners in Penrith. In the five years 1980-4, 1267 women began labour in Penrith, of whom 1153 (91%) never required help from a consultant unit. Ninety required transfer during labour. Ten mothers and four neonates required transfer during the early puerperium, all to one receiving unit in Carlisle. There were six perinatal deaths during the five years; five occurred in babies delivered after transfer. The perinatal mortality was 4.7/1000. The low mortality, the low level of intervention, and the preference of women all support the retention of isolated units. PMID- 3105726 TI - Inequalities in health in Britain: specific explanations in three Lancashire towns. AB - The reasons why mortality is higher in the poorer areas of Britain are largely unknown. Thus how to reduce inequalities in health is a matter of conjecture. In three neighbouring towns in northern England the rates of death from all causes differ greatly. Socioeconomic conditions in the towns are similar though below average for England and Wales. The pattern of disease specific rates was analysed and related to past differences in infant mortality. It is suggested that past differences in maternal health and physique and in the postnatal environment, particularly infant feeding, housing, and overcrowding, may be determinants of current differences in adult mortality. PMID- 3105725 TI - Phototherapy: the hospital as risk factor. AB - In a retrospective study over six years the incidence of phototherapy was examined in two groups of healthy neonates who were born spontaneously and at term in hospital. They were comparable in all respects except that one group was cared for at home and the other group was cared for in hospital. It appeared that the infants in hospital received phototherapy seven times more often than those at home, and surveillance at home was not inferior to that in hospital. There is no reason to assume that neonatal jaundice occurred more often in neonates in hospital than in those at home. Thus the difference in the frequency of treatment with phototherapy between the two groups is ascribed to the influence of the hospital environment, which may encourage intervention. PMID- 3105727 TI - ABC of 1 to 7 (revised). Bronchial asthma. PMID- 3105728 TI - Menorrhagia. PMID- 3105729 TI - Why doctors must grapple with health economics? PMID- 3105730 TI - Inadequacy of oleic acid in erythrocytes as a marker of malignancies. PMID- 3105731 TI - Dose dependent response of symptoms, pituitary, and bone to transdermal oestrogen in postmenopausal women. PMID- 3105732 TI - Head injuries in the elderly. PMID- 3105733 TI - Time for action on hepatitis B immunization. PMID- 3105734 TI - Identity cards for patients infected with HIV? PMID- 3105735 TI - Ulcerogenicity of piroxicam: an analysis of spontaneously reported data. PMID- 3105736 TI - Diagnostic classification of the aetiology of mental retardation in children. PMID- 3105737 TI - Relation between phenotype and banal melanocytic naevi. PMID- 3105738 TI - Stress hyperglycemia and cause of death in non-diabetic patients with myocardial infarction. PMID- 3105739 TI - Autologous blood transfusion. PMID- 3105740 TI - Ottorino Respighi: bacterial endocarditis in 1936. PMID- 3105741 TI - Consultant accountability. PMID- 3105743 TI - Nursing manpower. PMID- 3105742 TI - Abdominal aortic aneurysms. PMID- 3105744 TI - Long term urethral catheterisation in the elderly. PMID- 3105745 TI - Testing the sense of smell. PMID- 3105746 TI - Sterilisation and the mentally handicapped. PMID- 3105747 TI - Effect of protein restriction in insulin dependent diabetics at risk of nephropathy. AB - Persistent proteinuria is strongly associated with increased mortality in insulin dependent diabetes, and risk of this condition can be predicted many years in advance by subclinical increases in albumin excretion rate (microalbuminuria). Eight normotensive insulin dependent diabetics with microalbuminuria who had overnight albumin excretion rates of between 15 and 200 micrograms/min underwent a three week randomised crossover study of their normal protein diet (median 92 (range 55-117) g/day) and a low protein diet (47 (38-57) g/day). Both diets were isoenergetic, and the low protein diet was supplemented with calcium and phosphate. Median overnight albumin excretion rate fell from 23.0 (15.0-170.1) micrograms/min during the normal diet to 15.4 (4.1-97.8) micrograms/min during the low protein diet. No consistent change was found in urinary excretion of beta 2 microglobulin during the two diets. The reduction in albumin excretion rate was accompanied by a significant fall in median glomerular filtration rate and fractional renal clearance of albumin. Kidney volume remained unchanged. There were no significant changes in glycaemic control or arterial blood pressure. In these few patients restriction of dietary protein had a beneficial effect on microalbuminuria, independent of changes in glucose concentrations and arterial blood pressure. PMID- 3105749 TI - Infertile or childless by choice? A multipractice survey of women aged 35 and 50. AB - Eleven general practitioners examined the medical records of all women on their lists born in 1950 (617 patients) and 1935 (533 patients) to determine the prevalence of childlessness and specialist consultations about infertility. Eighty eight (14.3%) of the women born in 1950 and 41 (7.7%) of those born in 1935 were childless. Sixty eight women born in 1950 (11.0%) and 17 born in 1935 (3.2%) were considered childless by choice. Involuntary childlessness was found in 20 (3.3%) of the women born in 1950 and 24 (4.5%) born in 1935. Forty two (6.8%) of the women born in 1950 had consulted a specialist about infertility as compared with 19 (3.6%) born in 1935. This study found a significant increase in voluntary childlessness among the younger women; there was no evidence of a change in the prevalence of involuntary childlessness despite the increasing demand for specialist referral, which appeared to be made by women who were parous or destined to become so. PMID- 3105750 TI - Pressor effects of thyrotrophin releasing hormone during thyroid function testing. PMID- 3105748 TI - Does prophylactic thyroxine treatment after operation for non-toxic goitre influence thyroid size? AB - In order to evaluate the influence of thyroxine treatment on thyroid volume after thyroidectomy for non-toxic goitre 110 consecutive patients were randomised to receive thyroxine (150 micrograms daily) or no treatment three months after operation. Thyroid volume determined by ultrasonography did not differ significantly between the two groups one year after operation. Nevertheless, a similar decrease in volume was seen from three to 12 months postoperatively in the thyroxine treated and no treatment groups (median 18 (range 8-70) ml to 16 (range 7-57) ml, and median 20 (range 9-72) ml to 17 (range 8-58) ml, respectively). Three patients (two given thyroxine) had recurrence of goitre within the observation period of one year. In this series thyroid volume decreased during the first postoperative year independently of thyroxine treatment. Hence it seems questionable whether postoperative thyroid function studies can identify patients at risk of recurrence of goitre after operation for non-toxic goitre and whether routine postoperative treatment with thyroxine is justifiable. PMID- 3105751 TI - Chlorpromazine induced fluid retention masquerading as idiopathic oedema. PMID- 3105752 TI - Hepatic adenomas induced by norethisterone in patients receiving renal dialysis. PMID- 3105753 TI - Simulated patients in general practice: a different look at the consultation. AB - To develop a better empirical basis for developing quality assessment in general practice three simulated patients made appointments with 48 general practitioners during actual surgery hours and collected facts about their performance. The simulated patients were indistinguishable from real patients and presented a standardised story of a symptomatic urinary tract infection. Two months later the same general practitioners received a written simulation about a patient who had the same urinary tract infection and were asked how they would handle this in real practice. Both results were scored against an existing consensus standard. The overall score for both methods did not show any substantial differences. A more differentiated analysis, however, showed that general practitioners performed significantly better with simulated patients. It also showed that general practitioners answering the written simulation performed significantly more unnecessary and superfluous actions. The results of this study show that the use of simulated patients seems to show the efficient performance of general practitioners in practice. PMID- 3105754 TI - Case note chaos: prevention is better than cure. AB - The long term storage of hospital clinical records is becoming a big problem. A great reduction in the bulk of case notes can be achieved by compartmentalizing unstructured case notes. Such a system has many advantages for medical staff, and its widespread use would do much to alleviate storage problems in future years. PMID- 3105755 TI - Primary and secondary amenorrhoea. PMID- 3105756 TI - Portraits from memory. 10--Dr Thomas K Buchan (1885-1958). PMID- 3105757 TI - Testing for HIV without permission. PMID- 3105758 TI - Torsion of the testis: why is the prognosis so poor? AB - The cases of 83 boys who were admitted to hospital with acute testicular pain or swelling were studied. Twenty seven had torsion of the testis, and 15 (55%) of these lost a testis. The main reason for the poor results was delay by the patient or his parents in seeking medical attention. PMID- 3105759 TI - Sterilisation of mentally handicapped woman. PMID- 3105760 TI - ABC of 1 to 7 (revised). Sleep problems. PMID- 3105761 TI - Childhood leukemia and nuclear establishments. PMID- 3105762 TI - Respiration and connective tissue diseases. PMID- 3105763 TI - Reye's syndrome: an assessment of intracranial monitoring. PMID- 3105764 TI - Prejudice against doctors and students from ethnic minorities. PMID- 3105765 TI - Prejudice against women doctors. PMID- 3105766 TI - Early emergency care. PMID- 3105767 TI - AIDS counselling and informed consent. PMID- 3105768 TI - Phototherapy and dithranol treatment of psoriasis. PMID- 3105769 TI - Tennis elbow: conservative, surgical, and manipulative treatment. PMID- 3105770 TI - Portraits from memory: Dr E C Smith. PMID- 3105771 TI - Age and infertility. PMID- 3105772 TI - Major crush injury. PMID- 3105773 TI - Collagenous colitis: disease or diversion? PMID- 3105774 TI - Doctors' ignorance of statistics. PMID- 3105775 TI - Hypochondriasis: an acceptable diagnosis? PMID- 3105776 TI - Inequalities and the new Health Education Authority. PMID- 3105777 TI - Clinically apparent eating disorders in young diabetic women: associations with painful neuropathy and other complications. AB - Of 208 young women with insulin dependent diabetes, 15 (7%) had a clinically apparent eating disorder (anorexia nervosa or bulimia), a much higher prevalence than reported in non-diabetic women. Most, but not all, of these patients had a long history of poor glycaemic control. In contrast with previous suggestions, control did not deteriorate after the onset of the eating disorder. There was a high incidence and an early onset of diabetic complications. Eleven of the 15 patients had retinopathy, six with proliferative changes; six had nephropathy; and six neuropathy. Most strikingly, four patients with anorexia nervosa developed acute painful polyneuropathy. In each case pain started when the eating disorder developed, almost coinciding with the peak of weight reduction. Remission of pain occurred as weight was regained. The symptoms were accompanied by abnormalities in peripheral nerve electrophysiology and autonomic nerve function, some improvements in which accompanied weight recovery. It is suggested that nutritional factors may contribute to the high rate of early onset diabetic complications, particularly neuropathy. PMID- 3105778 TI - Parents' perceptions of food intolerance in primary school children. AB - In a study of about 7000 children, parents' perceptions were used to examine the prevalence of food intolerance, the types of food implicated, the association of intolerance with diseases, and the social background of those identified as being food intolerant. One hundred and ninety two children (3%) were perceived as being food intolerant, with a further 105 (2%) being classed as intolerant under a less stringent definition of intolerance. For 128 (67%) of these children a doctor was consulted. The pattern of food avoided was very similar in children for whom the decision to exclude certain foods was made by health staff and in those for whom the parents themselves made decisions about their child's diet. A strong association was seen between the mother's level of education and the child being perceived as being food intolerant. Between 20% and 30% of children with a disease associated with food intolerance--for example, eczema--had currently or previously avoided some types of food. The results of this study emphasise the need to develop criteria to tackle the growing demand for National Health Service treatment by parents who believe their child to be food intolerant. PMID- 3105779 TI - Impaired responsiveness of homosexual men with HIV antibodies to plasma derived hepatitis B vaccine. AB - Thirty five homosexual men (17 positive for antibody to the human immunodeficiency virus (HIV) and 18 consistently negative) were vaccinated against hepatitis B virus infection. Eight of the 17 seropositive patients failed to develop detectable hepatitis B surface antibody within three months of the third injection compared with only one of the 18 seronegative patients (p less than 0.01). HIV infection is prevalent in the developed world in groups at risk for hepatitis B infection and in certain Third World countries where widespread vaccination programmes exist. This study shows the impact that coincident HIV infection may have on an otherwise efficacious vaccine. The efficacy of this and other vaccines in patients infected with HIV needs to be studied urgently. PMID- 3105781 TI - A forgotten factor in pelvic inflammatory disease: infection in the male partner. PMID- 3105780 TI - From persistent generalised lymphadenopathy to AIDS: who will progress? PMID- 3105782 TI - Adverse reactions to drugs in children. PMID- 3105783 TI - Be your own coroner: an audit of 500 consecutive deaths in a general practice. AB - General practitioners' medical records of a geographically defined population of about 1600-1800 have been retained since 1964. Details of care by general practitioners and hospital correspondence were available for 500 deaths (277 men, 223 women) from 1964 to 1985, including deaths at home, at work, in the street, in short term and long term institutional care, and within six months of release from institutional care. The periods 1964-73 and 1974-85 were compared. The proportion of men aged greater than or equal to 80 who died increased from 20 (14%) in 1964-73 to 22 (16%) in 1974-85, but the proportion of women aged greater than or equal to 80 who died increased from 21 (23%) to 50 (39%). Of all deaths, 223 (45%) were thought to have had avoidable causal factors, of which 132 (59%) were attributed to patients, 45 (20%) to the general practitioner, 9 (4%) to hospitals, and 37 (17%) to others. The number of deaths related to smoking decreased from 31 (43%) in men aged less than 70 to 19 (30%) but in women aged less than 70 increased from 4 (10%) to 11 (26%). The proportion of deaths in women who were already dependent six months before death increased from 55 (58%) to 81 (63%) but in men remained constant at 64 (46%) in the first period and 62 (46%) in the second. Nearly two thirds of all deaths occurred at home in both periods--about twice the proportion for England and Wales--but the proportion of men dying at home decreased from 87 (62%) to 76 (56%). A critical analysis of deaths in whole populations by primary care teams can identify changes that are needed both in the work and organisation of the team and in the behaviour of the population itself. PMID- 3105784 TI - Information for managers in hospitals: representing maternity unit statistics graphically. AB - Staff who organise and run maternity units contribute many statistics to their health authority but do not find it easy to obtain information about their unit from these statistics. Data that are collected routinely, however, can be used to provide each unit with a graphical profile of its activity and resources. The method described here was derived from the personality profiles used by psychologists and allows staff in one unit to assess the outcome, activity, and use of resources in their unit in relation to similar units, to explain some of the differences when these occur, or to highlight potential problems. Examples are taken from a study of maternity units in the West Midlands. It is concluded that the technique can indicate potential problems and usefully be adopted by those who monitor maternity care in districts or hospitals. PMID- 3105785 TI - Social factors and disease: the medical perspective. PMID- 3105786 TI - ABC of 1 to 7 (revised). Services for children: primary care. PMID- 3105787 TI - Infertility. PMID- 3105788 TI - LMSSA: a back door entry into medicine? PMID- 3105790 TI - Drums begin to beat in the waiting list jungle. PMID- 3105789 TI - Public knowledge about AIDS increasing. PMID- 3105791 TI - Dangers from dissolution of latex in Celestin endo-esophageal tube. PMID- 3105792 TI - Assault on a GP. PMID- 3105793 TI - Effect of chloroquine on insulin and glucose homeostasis in normal subjects and patients with non-insulin dependent diabetes mellitus. PMID- 3105794 TI - Alcohol and violence. PMID- 3105795 TI - Effect of dietary cholesterol on plasma cholesterol concentration. PMID- 3105796 TI - Better reporting of adverse drug reactions. PMID- 3105797 TI - Adverse reaction monitoring using cohort identification. PMID- 3105798 TI - Future of the pathologist in an era of technological change and cost containment. PMID- 3105799 TI - Open access to orthopedic appliances for general practitioners. PMID- 3105800 TI - Restless legs syndrome. PMID- 3105801 TI - Epidural morphine for outpatients with severe anginal pain. PMID- 3105802 TI - Treating postural hypotension. PMID- 3105803 TI - Social future of elderly admitted to acute care hospital. PMID- 3105804 TI - What contribution has cardiac surgery made to the decline in mortality from coronary heart disease? PMID- 3105805 TI - Outbreak of Weil's disease in a food fad commune in India. PMID- 3105806 TI - Immunoscintigraphy of metastases with radiolabelled human antibodies. PMID- 3105807 TI - Medical staffing and training in the West Midlands region. PMID- 3105808 TI - Gustatory hallucinations in epileptic seizures. Electrophysiological, clinical and anatomical correlates. AB - Of the 718 patients investigated for intractable epilepsy by stereoelectrocencephalographic (SEEG) exploration, 30 (4%) manifested gustatory hallucinations as part of their seizures. In 20 patients, it was possible to make some electrophysiological, clinical and anatomical correlates. Gustatory hallucinations occurred as one manifestation of parietal, temporal or temporoparietal seizures. A brief isolated gustatory hallucination was induced mainly by electrical stimulation of the parietal or rolandic opercula in patients with gustatory seizures, in 1 epileptic patient with parietotemporal epilepsy who had never experienced gustatory hallucinations and in another with temporal lobe epilepsy with no history of gustatory manifestations. The electrically-induced seizures, which included a gustatory hallucination as one of the ictal events, were obtained mainly by stimulation of the hippocampus and amygdala. The associated ictal events of a seizure with gustatory manifestations differed depending upon the origin of the seizure. During parietal seizures, they consisted of staring reactions, clonic contractions of the face, deviation of the eyes and salivation. During temporal lobe seizures, the associated events included mainly oral movements, autonomic disturbances, purposeless movements and epigastric or other abdominal symptoms. Seizures affecting both the infra- and suprasylvian regions were characterized by symptoms of both categories listed above. Emotional disturbances were observed mainly when there was an involvement of the cingulate gyrus. When care was taken to avoid methodological errors in the interpretation of the clinical signs occurring after electrical stimulation, it became clear that gustatory hallucinations in man were related to the disorganization of the parietal and/or rolandic operculum. electrically-induced temporal lobe seizures which included gustatory hallucinations as an ictal event probably spread to the opercular region by a functional reorganization of the connections within these epileptogenic areas. PMID- 3105809 TI - Amphibian optokinetic after nystagmus: properties and comparative analysis in various species. AB - Optokinetic nystagmus and after nystagmus were studied in six amphibian species, three urodeles and three anurans. It was demonstrated that two of the urodeles, Hydromantes italicus and Salamandra salamandra, display a relatively well developed optokinetic after nystagmus, which is less pronounced in Bombina variegata and nearly absent in Bufo bufo, Rana temporaria, and Tylototriton verrucosus. These results indicate a certain degree of velocity storage in the optokinetic reflex of some amphibians. PMID- 3105810 TI - Noradrenergic and dopaminergic modulation of thyrotropin secretion in the rat. AB - Noradrenergic and dopaminergic regulation of thyrotropin (TSH) secretion was investigated in adult male Wistar rats. TSH secretion displayed a circadian variation with peak serum TSH levels at 10.00 h. The alpha 2-adrenoceptor agonist, clonidine (250 micrograms/kg, i.p.), was found to cause an enhancement of serum TSH levels at 10.00 h (160 +/- 10% of control values, P less than 0.001) which was antagonized by prior administration of the alpha 2-adrenoceptor antagonist, yohimbine (3 mg/kg, i.p.). The alpha-adrenoceptor antagonist phentolamine caused a significant decrease in serum TSH levels at 10.00 h (62 +/- 15% of control values, P less than 0.05) at a dosage of 2 mg/kg, i.p. The alpha 1 adrenoceptor agonist, phenylephrine (0.2 or 2 mg/kg, i.p.), was without effect as were the dopaminergic receptor agonist, apomorphine (1 or 5 mg/kg, i.p.), and the antagonist, sulpiride (20 mg/kg, i.p.). The beta-adrenoceptor agonist, isoproterenol (1 mg/kg, i.p.) was found to cause a decrease in serum TSH levels at 10.00 h (70 +/- 16% of control levels, P less than 0.01), which was completely antagonized by prior administration of the beta-adrenoceptor antagonist, propranolol (10 mg/kg, i.p.). TSH-releasing hormone (TRH, 5 micrograms/kg, i.v.) caused a significant stimulation of TSH secretion (470 +/- 63% of basal levels, P less than 0.001), which was not affected by prior treatment of the rats with yohimbine (0.1 mg/kg, i.p.), phentolamine (2 mg/kg, i.p.), propranolol (10 mg/kg, i.p.) or sulpiride (20 mg/kg, i.p.). There was, however, a tendency towards a decrease in the TRH-stimulated release of TSH in rats pretreated with phentolamine or propranolol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105811 TI - Melatonin, 5-methoxytryptamine and some of their analogs as cyclo-oxygenase inhibitors in rat medial basal hypothalamus. AB - Melatonin, and its analogs 6-chloro- and 6-fluoromelatonin inhibited in a dose dependent way (10(-8)-10(-5) M) labeled prostaglandin (PG) E2, PGF2 alpha, thromboxane (Tx) B2 and 6-keto-PGF1 alpha production from [14C]arachidonate by rat medial basal hypothalamus (MBH). 5-Methoxytryptamine also depressed arachidonate metabolism; at 10(-8) M concentrations the effect of 5 methoxytryptamine on PGE2, PGF2 alpha and TxB2 synthesis (93-96% inhibition), and 6-keto-PGF1 alpha (75% inhibition) was greater than that observed for melatonin (51-56% and 44% inhibition, respectively). Neither 6-hydroxymelatonin nor serotonin affected MBH cyclo-oxygenase pathway in vitro. PMID- 3105812 TI - Catecholamines and conditioned blocking: effects of ventral tegmental, septal and frontal 6-hydroxydopamine lesions in rats. AB - The performance of rats on the conditioned blocking test of learned inattention was measured in a two-way shuttle avoidance task after sham and dopamine (DA) depleting lesions of the frontal cortex, septum and ventral tegmental area (VTA). Animals were trained on two sessions with tone and/or light as conditioned stimuli. One group was trained with both stimuli on both sessions. A second group was trained on the first session with one stimulus and on the second with both stimuli. The blocking of conditioning to the added stimulus (b) was tested by presenting the stimuli (a and b) separately and measuring the blocking ratio (avoidance to b/a + b) and response latencies. No deficits were recorded on tests of sensory and motor ability. The VTA group alone showed a hyperlocomotor response to apomorphine treatment and did not acquire the avoidance response. The appearance of blocking in the septal group was delayed until the end of the test session. Blocking was mildly attenuated in the frontal group. DA levels were depleted by about 80% and noradrenaline (NA) levels by, respectively, 20 and 50% in frontal and septal areas. This suggests that the level of DA activity or the balance between the activity of DA and NA in frontal and limbic regions can contribute to efficient associative conditioning and/or the normal ability of rats not to attend to a redundant stimulus. PMID- 3105813 TI - Modulation of oxytocin secretion by ascending noradrenergic pathways: sexual dimorphism in rats. AB - We have investigated the role of ascending noradrenergic pathways in the control of oxytocin (OT) and arginine-vasopressin (AVP) secretion during acute immobilization stress in male and female rats. 6-Hydroxydopamine-induced lesions of the ventral noradrenergic bundle (VNAB) resulted in a selective depletion of hypothalamic noradrenaline content. In sham-lesioned rats plasma levels of OT were raised following stress, the response being significantly greater in female compared with male animals. VNAB lesions were not associated with altered responses in female rats, whereas lesioned males exhibited markedly elevated OT stress responses. AVP secretion was not modulated in VNAB-lesioned rats of either sex. The results provide functional evidence of a sexually dimorphic inhibitory role of the VNAB in the control of OT secretion. PMID- 3105814 TI - Brain neurons develop in a serum and glial free environment: effects of transferrin, insulin, insulin-like growth factor-I and thyroid hormone on neuronal survival, growth and differentiation. AB - We have developed a pure cortical neuronal culture free of glial cells, grown in a serum-free environment. The cultured cells immunostained positively with neurofilament antibody while they displayed virtually no glial cell characteristics, such as glial fibrillary acidic protein, glycerol phosphate dehydrogenase or glutamine synthetase. Insulin and transferrin were necessary and sufficient for neuronal survival, neurite extension and glutamic acid decarboxylase (GAD) expression. Insulin-like growth factor-I was able to replace insulin and was active close to its physiological concentration, suggesting it might be the in vivo factor influencing neuronal growth in the brain. The dynamics of the developmental process were striking. The neurons moved on the poly-D-lysine covered plastic dish, and rearrangements in contacts between cells were observed. At first the neurons underwent a general cellular growth manifested by a large increase in the culture total protein content and by the initiation of neurites. A more specific differentiation, as indicated by the sharp increase in GAD levels which was concurrent with an increase in interneuronal contacts, lagged behind the initial growth. Thyroid hormone (TH) affected the differentiation process, causing a future increase in GAD levels during the same time of increase in neurite growth, in interneuronal contacts, in thyroid hormone receptors and thyroid gland maturation. Removal of each of the hormones after a few days of cell growth revealed that transferrin was still required for neuronal survival while insulin became essential for general cellular growth but not specific neuronal differentiation, since it caused an increase in both the total protein and GAD levels but not in GAD specific activity. TH, on the other hand, affected the differentiation process as evident by its ability to increase GAD specific activity. This action of TH, however, required the presence of insulin, without which no increase in GAD level by TH was observed. This neuronal culture, glial and serum-free, provides a new system for investigating neuronal development and function in the complex mammalian central nervous system. PMID- 3105815 TI - Peripheral nerve carbonic anhydrase activity and chronic acetazolamide treatment of rats. AB - Examination of cranial nerves shows that the sensory infraorbital branch of the trigeminal nerve contains many carbonic anhydrase-reactive axons whereas axons of the motor facial nerve are non-reactive. This motor/sensory axon staining difference holds for both cranial and spinal nerves. Chronic treatment with acetazolamide produced no apparent changes in carbonic anhydrase histochemical activity or the structure of peripheral nerve fibers. PMID- 3105817 TI - The cytoskeleton of the human cerebellar cortex: an immunohistochemical study of normal and pathological material. AB - Monoclonal antibodies to non-phosphorylated and phosphorylated neurofilaments, as well as monoclonal and polyclonal antibodies to other cytoskeletal elements, were applied to the study of the cerebellar cortex of normal and pathological human material. The methods proved to be applicable to formalin fixed paraffin embedded tissue, provided the period of formalin fixation was short. The main difference between normal and pathological material was found in Purkinje cells and their dendrites. While normal Purkinje perikarya and dendrites expressed only non phosphorylated neurofilaments, reactive dendrites stained more intensely with antibodies to phosphorylated neurofilaments. Similar observations were made on the abnormal dendritic ramifications of the partially deafferented, hypertrophic, inferior olive. The significance of the appearance of phosphorylated neurofilament epitopes in abnormal dendrites remains unknown and requires further investigation. PMID- 3105816 TI - Suppression of neurofilament degradation by protease inhibitors in experimental spinal cord injury. AB - Intraperitoneal administration of the neutral protease inhibitors leupeptin and E 64c substantially suppressed the degradation of neurofilament proteins (NFP) at the site of mechanical insult and secondary axonal degeneration, and facilitated the recovery of motor functions in acute spinal cord injury in rats. The drug effects were assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis of NFP fractions from the injured tissue and by morphometry of degenerating axons revealed by the Fink-Heimer method in distal spinal cord segments with the aid of an automated image analyzer. The role of calcium activated neutral proteases in acute central nervous tissue damage and potential use of protease inhibitors as therapeutic modalities are discussed. PMID- 3105818 TI - Kindling antagonism: a role for hindbrain norepinephrine in the development of site suppression following concurrent, alternate stimulation. AB - The concurrent, alternate electrical stimulation of the septal nucleus and the entorhinal cortex results in the development of fully generalized seizures at one site (dominant site) and the lack of development of kindled seizures at the other (suppressed or antagonized site). We have labeled this phenomenon kindling antagonism. Previous work from our laboratory has demonstrated that the whole brain depletion of norepinephrine (NE) eliminates the development of kindling antagonism. In the present study animals were treated with the neurotoxin 6 hydroxydopamine (6-OHDA) as neonates. The neonatal administration of 6-OHDA produced robust increases in brainstem and cerebellar NE levels and depletions of forebrain NE levels when assayed at maturity. Striatal dopamine levels were spared by this treatment. Neonatal 6-OHDA did not alter the development of the kindling antagonism phenomenon which is typically observed following concurrent, alternate stimulation of the septal nucleus and entorhinal cortex. Neonatal 6 OHDA treatment significantly facilitated the rate of kindled seizure development at dominant sites but failed to alter thresholds for the elicitation of afterdischarges (AD) or patterns of development of AD durations. Other characteristics of kindling antagonism were similarly unaffected by 6-OHDA treatment. These data suggest that brainstem and/or cerebellar NE are sufficient to mediate the development of kindling antagonism in the relative absence of forebrain NE. PMID- 3105819 TI - Spontaneous and graft-induced behavioral recovery after 6-hydroxydopamine lesion of the nucleus accumbens in the rat. AB - In the present study the long-term evolution of behavioral deficits following a local lesion of the dopaminergic innervation of the nucleus accumbens with 6 hydroxydopamine (6-OHDA) was compared in two groups of rats: lesioned animals and animals bearing a dopaminergic implant in the nucleus accumbens. Lesioned animals gradually recovered on various behavioral tests (amphetamine-induced locomotion, exploration, hoarding) and were indistinguishable from the control group on most parameters by 10 months postlesion. The deficits were, however, reinstated by a second intra-accumbens 6-OHDA lesion, a finding which suggests a role for dopaminergic reinnervation in the observed recovery. Conversely, grafted animals still displayed marked deficits even 10 months after grafting, although the lesioned areas were well reinnervated by the graft. These results indicate that the graft, while being unable on its own to compensate for part of the deficits, can nevertheless impair and compete with endogenous processes leading to behavioral recovery following a local lesion. PMID- 3105820 TI - Timing of 6-hydroxydopamine administration influences its effects on visual cortical plasticity. AB - We recorded from the visual cortex of 4 groups of monocularly deprived kittens. Three groups were treated with intraventricular 6-hydroxydopamine (6-OHDA) at different times relative to monocular deprivation (MD). One group received only vehicle solution and MD. 6-OHDA caused the greatest decrease in plasticity in the kittens receiving 6-OHDA throughout the deprivation period; that is, these kittens were the least affected by MD. 6-OHDA caused a smaller decrease in plasticity in kittens receiving 6-OHDA just prior to eyelid suture and a still smaller decrease in kittens waiting a week between 6-OHDA treatment and eyelid suture. The kittens in all groups receiving 6-OHDA were equally depleted of norepinephrine (NE). We conclude that 6-OHDA decreases plasticity in the visual cortex; however, the time course of this decrease is better related to the time course of the 6-OHDA treatment than to the time course of NE depletion. PMID- 3105821 TI - 6-Hydroxydopamine induces serotonergic axon sprouting in cerebral cortex of newborn rat. AB - Newborn rats were administered the neurotoxin 6-hydroxydopamine (6-OHDA) to determine whether neonatal ablation of the noradrenergic (NE) innervation produces augmented growth (i.e., sprouting) of serotonergic (5-HT) raphe-cortical axons. Following NE denervation at birth, the density of 5-HT axons in motor cortex (AG1) was determined at 4 days postnatal. Using a computer microscope system, the positions of all 5-HT-positive axons were mapped in radial strips of cortex from treated and control rats. Cumulative axon length, expressed as a function of area inspected, was used as a parameter of innervation density. Following 6-hydroxydopamine, the cumulative length of 5-HT axons in motor cortex increases by 32% (P less than 0.05) while cortical serotonin levels measured by HPLC concomitantly increase by 29% (P less than 0.005). The combined increases in 5-HT axon density and in neurotransmitter levels indicate that NE denervation produces increased growth of the cortical 5-HT innervation by the 4th postnatal day. The amount of transmitter stored per unit length of 5-HT axons appears unchanged. In 6-OHDA-treated rats, 5-HT axons exhibit augmented growth in all layers of motor cortex. In the treated rats, the relative density of 5-HT axons in each cortical layer is roughly proportional to the normal innervation density. Accordingly, in motor cortex, the magnitude of 5-HT axon sprouting is greatest in layer VI, which normally receives a dense 5-HT innervation, and is less in layer V, which has a lower innervation density. Qualitative assessment of other cortical areas following 6-OHDA reveals that 5-HT axon density appears increased in cortical zones that normally receive a dense 5-HT innervation, while the density remains low in zones with sparse innervation. The absence of axonal sprouting is particularly striking in those zones which receive a dense NE innervation but are sparsely innervated by 5-HT axons. Thus, while 5-HT axons undergo sprouting, they do not appear to replace ablated NE terminals in areas with a sparse 5-HT innervation. Hence, normal laminar and regional specificity of 5-HT axons is preserved despite ablation of NE afferents. These data indicate that, while NE denervation may trigger serotonergic sprouting, competition between NE and 5-HT fibers for the same postsynaptic sites is not the main factor that regulates postnatal growth of these axonal projections. The present findings demonstrate that the early development of raphe-cortical projections is influenced by NE cortical innervation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3105823 TI - [Mitochondrial oxidative phosphorylation in the rat kidney during the perinatal period]. AB - Oxidative metabolism in the developing rat kidney has been studied on isolated mitochondria. An increase of about 50% in state 3 respiration has been observed at birth, using succinate, glutamate, or palmitoyl-L-carnitine as a substrate. The rate of respiration in the presence of 2,4-dinitrophenol was found identical to state 3 respiration in all cases. Cytochrome oxidase activity did not change between the fetal and newborn stages. The increase of mitochondrial respiration revealed here, which is not linked to a modification of the respiratory chain, could be involved in the rise of kidney ATP level and energy charge observed at birth. PMID- 3105822 TI - [Intracellular localization of beryllium by analytical ion microscopy]. AB - After injection in the rat of a soluble beryllium salt, the distribution of this element was studied at the subcellular level by analytical ion microscopy. Beryllium is concentrated inside the nuclei with a particular affinity for the nuclei of the proximal tubule cells of the kidney. The same tissue was studied by electron microscopy and abnormal intranuclear inclusions were observed in the same variety of cells. PMID- 3105825 TI - [Participation of the rostral portion of the spinal nucleus of the trigeminal sensory complex in nociception]. AB - Single unit responses elicited through noxious mechanical stimulation of orofacial receptive fields were recorded, with glass micro-electrodes, within the rat ventrobasal complex of the thalamus. The evoked activities were compared before and after de-afferentation of the caudal sub-nucleus by trigeminal tractotomy at the level of the obex. Only units responding to noxious stimulation of oral receptive fields were unaffected by tractotomy. These results provide evidence that the rostral part of the spinal nucleus is involved in trigeminal painful sensation. PMID- 3105824 TI - [Effect of the nature of carbohydrates in pig diets on the intestinal absorption of volatile fatty acids]. AB - The appearance of nutrients (amino nitrogen and reducing sugars) and microbial metabolites (volatile fatty acids, VFA) was measured quantitatively in five pigs. After ingestion of a semi-synthetic diet (RFL) containing 22% lucerne meal (6% crude fibre), the absorption of reducing sugars (RS) in the small intestine was high (97.8%) and that of VFA low (880 +/- mmoles/24 hrs.). Ingestion of a semi synthetic diet (RLa) containing 22% lactose and 6% purified cellulose led to lower absorption of RS (85.2%) and a higher absorption of VFA (1,180 +/- mmoles/24 hrs). PMID- 3105826 TI - [A statistical model for interpreting the antibiogram]. AB - Up to now, to interpret antibiotic susceptibility tests, the common practice has been to use: first, breakpoints without any quantitative justification, secondly, concordance curves between the different measurement techniques; these are not well adapted to the heterogeneous character of bacterial populations. We hereby propose another method: it is based on a global data analysis for each bacterial species, each antibiotic family and each measurement technique. So, we have drawn up a new model for the interpretation, both global and data-processed; it is based on qualifying classes, which are obtained and interpreted by hierarchical ascendent classification, principal components analysis, and comparison with pharmacological data. It can be used by any biologist. What is more, justified breakpoints with a numerical risk and quality control are defined. There are also some additional uses: evaluation of the effect of new antibiotics, standardization of new measurement techniques, detection of the emergence of new bacterial resistance in patients, guidance for research into unknown resistance mechanisms and characters. PMID- 3105828 TI - Mechanism of vertical transmission of the dengue virus in mosquitoes. AB - Both experimental and field data suggest that some tropical mosquito-borne flaviviruses, such as dengue and yellow fever, survive dry seasons by vertical (i.e. transgenerational) transmission in their mosquito hosts. Although vertical transmission of arboviruses in mosquitoes is considered to be transovarial in nature, observations reported here indicate that this is probably not true for dengue virus. Rather, infection of the next generation with this virus apparently takes place when the fully developed egg, enclosed in the chorion, is fertilized at the time of oviposition. In contrast to transovarial transmission, the latter mechanism permits the infection of progeny following a single maternal blood meal. PMID- 3105829 TI - [Characterization by cytofluorometry of the different types of adenohypophyseal cells in the rat]. AB - The different antehypophysical cell types which synthetize and release somatotroph (GH), corticothroph (ACTH), gonadotroph (LH-FSH) and lactotroph (PRL) hormones were analysed. The experiments were performed on hypophyses from five groups of animals: adult males, 14 days-old female, adult females, gestating adult females and lactating adult females. The cells were analysed by immunofluorescence using flow cytometry. For each of the hormones studied, there was a characteristic spectral distribution of cells. The evolution of cell size and granular content with respect to sex and physiological state of each group was studied by the analysis of diffused light. Small, slightly granular cells represented 50% of the cell population in males and 14 day-old females but only 8% in gestating or lactating females. The study of the cell cycle showed the presence of dividing cells in the population of large, granular cells from gestating and from lactating females. No features of cell division were observed in the population of small, slightly granular cells. This study indicates the potential value of multiparametric analysis in the separation of pure sub populations of antehypophysial cells. PMID- 3105827 TI - [Production of enkephalins by the human and bovine corpus luteum]. AB - In search of early pregnancy factors, we detected by radioimmunoassay the presence of enkephalin in bovine and human corpus luteum. In vitro met-enkephalin release by bovine corpus luteum is about 0.5 to 1 pmole/mg of fresh tissue/24 hrs. The content of the fresh tissue is between 0.7 and 1.9 pmoles per gram of human tissue, and 0.9 pmoles for bovine tissue. Furthermore, we determined the presence of leu-enkephalin and met-enkephalin Arg-Gly-Leu to. The ratios observed confirm a pro-enkephalin A expression in the ovary. Opiates or opioid-like peptides are present in the female genitalia at the time of early embryo development. The roles of these opioid peptides is discussed in term of ovum transport, granulosa cell physiology and early pregnancy factors. PMID- 3105830 TI - [In vitro translation of RNA extracted from corpuscules of Stannius of the eel (Anguilla anguilla); identification of the precursor of parathyrin in the corpuscules of Stannius (PCS)]. AB - Corpuscles of Stannius (CS) of Teleosts secrete a PTH like hormone (Parathyrin of CS: PCS) which is involved in calcium metabolism by acting mainly at the gill level. Translated products encoded by mRNA extracted from Eel Corpuscles of Stannius and among these, translated products immunoprecipitated by anti b-PTH immunserum were compared to the products synthetized during incubation of the glands with labelled methionine. The analysis was performed by polyacrylamide gel electrophoresis and fluorography. Biosynthesis of the PCS involves a mRNA encoding for a 45 kD precursor which is immunoprecipitated by anti b-PTH immunserum and totally displaced from antibody, either by 1-34 h-PTH or by purified PCS. PMID- 3105831 TI - [Hemodynamic parameters and blood-free surgical field with nitroglycerin in maxillofacial surgery]. AB - 73 oral facial surgery have been performed using controlled-hypotension induced with nitroglycerin (NTG) to reduce surgical bleeding. Surgical bleeding has been reduced in more than 45% of cases. But frequent lack of correlation between blood pressure, heart beat and bleeding might imply vascular reflex mechanisms induced by controlled-hypotension using NTG. Hemodynamic parameters such as blood pressure and heart rate seem to be insufficient to monitor controlled hypotension efficiency on surgical bleeding. The use of peroperative tissues blood flow monitoring may help for the better understanding of surgical bleeding during controlled-hypotension using NTG. PMID- 3105832 TI - Effects of vitamin D deficiency in the chicken embryo. AB - Vitamin D-deficient chicken embryos were obtained by feeding laying hens a diet in which 5 micrograms 1,25(OH)2D3/kg feed were substituted for the vitamin D3 supplement in the control diet. Hatchability, total Ca and inorganic P concentration in blood, and tibial ash/dry weight ratio were determined in the vitamin D-deficient embryos and in embryos obtained from hens fed the control diet supplemented with 1100 IU vitamin D3/kg feed. After 5 weeks on the substituted diet the hens laid eggs that showed decreased hatchability in spite of excellent shell quality. All determinations in blood and bones were made on embryos of eggs laid after 6-12 weeks on the diets. On the 17th day of incubation the embryos derived from hens fed the substituted diet showed significant hypocalcemia and hyperphosphatemia and a low tibial ash/dry weight ratio. Injection of 1,25(OH)2D3 3 days before killing corrected the hypocalcemia of the deficient embryos. Those chicks that managed to hatch had normal levels of calcium and inorganic phosphate 1 day after hatching. These findings support previous suggestions by us and other authors that vitamin D metabolites are required by the embryo in order to mobilize calcium from the shell, and decreased hatchability in vitamin D-deficient embryos is related to a defect in calcium mobilization from the shell. While in previous studies a decrease in hatchability was the only parameter used to judge D deficiency of the embryos in our present studies, the deficiency is confirmed by demonstrating a deficit in mineral metabolism which is a more specific sign of D deficiency. PMID- 3105833 TI - Failure of oral calcium to enhance the acute antiosteolytic effect of calcitonin. PMID- 3105834 TI - The definition and diagnosis of osteoporosis. PMID- 3105835 TI - Increased trabecular bone density due to bone-loading exercises in postmenopausal osteoporotic women. AB - A program of diverse and dynamic loading exercises of the distal forearm, a common site of osteoporotic fractures, was applied three times a week for 5 months to 14 postmenopausal osteoporotic women. Two parameters were used to assess the effect of the exercises on bone mass. The mass density of bone (g/cm3) was measured by the Compton scattering technique. The bone mineral content (g/cm2) was measured by single photon absorptiometry. Both measurements were taken at the same location in the distal radius 1 year prior to the exercise period, at its beginning, and at its end, in both the exercised group and a matched control group of 26 osteoporotic women. During the exercise period the mean bone density decreased by 1.9% in the control group whereas it increased by 3.8% in the exercise group. The bone mineral content results did not demonstrate any significant trend over the whole period of the study. It is concluded that the trabecular bone tissue in the distal radius of postmenopausal osteoporotic women responds favorably to dynamic and diverse bone stressing exercises even in the seventh decade of life. PMID- 3105836 TI - Calcium phosphate saturation levels in ultrafiltered serum. AB - Calcifications occurring in arteriosclerotic plaque and other pathological deposits are important health concerns, and the nature of these deposits and their mechanisms of formation warrant investigation. Crystals of the relevant calcium phosphates were equilibrated with the undiluted ultrafiltered human serum (u.f.s.) at 37 degrees C by constant stirring and periodically removing samples for calcium and phosphate analysis and for pH measurement. The solubility measurements were carried out both with and without a 5.5% CO2 atmosphere, the physiological partial pressure of CO2. The apparent ion activity products of well crystallized dicalcium phosphate dihydrate (DCPD), octacalcium phosphate (OCP), and hydroxyapatite (OHAp) equilibrated in u.f.s. were calculated from the calcium and phosphate concentrations and pH in each case for comparison with their known solubility products. In this way the well-crystallized calcium phosphates serve as fiducial solubility standards, thereby minimizing errors due to complexing of calcium and phosphate ions by u.f.s. constituents. Under 5.5%, CO2 native u.f.s. was found to be substantially undersaturated with respect to DCPD, slightly supersaturated with respect to OCP, and highly supersaturated with respect to OHAp. The ion activity product of DCPD in DCPD-saturated u.f.s. was 2.4 X 10(-7), and the ion activity product of OCP in OCP-saturated u.f.s. was 4 X 10(-49), slightly above their solubility products (Ksp(DCPD) = 2.3 X 10(-7), Ksp(OCP) = 2.5 X 10(-49). The ion activity products of DCPD and OCP in u.f.s. under CO2 indicate that the concentrations of calcium and phosphate complexing agents (except bicarbonate) are quite low. The u.f.s. remained supersaturated with respect to OHAp even after 2 months of equilibration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105837 TI - Triamterene and renal stone formation: the influence of triamterene and triamterene stones on calcium oxalate crystallization. AB - A constant composition method has been used to compare the effects of triamterene renal stone material, synthetic triamterene precipitates, and soluble triamterene on the nucleation and crystallization kinetics of calcium oxalate in aqueous solution in vitro. Crystallization studies have been carried out with the concentrations of calcium and oxalate ions maintained constant by the potentiometrically controlled addition of concentrated reagent solutions containing these ions. Triamterene renal stones were found to be much less effective than synthetic triamterene towards promoting the nucleation and crystallization of calcium oxalate from supersaturated solution. Renal stones composed of triamterene and matrix did not significantly enhance the deposition of calcium oxalate compared to nonseeded controls. The triamterene stones were also found to be ineffective in promoting calcium oxalate crystallization compared to other precipitates thought to be involved in the etiology of stone disease such as calcium hydroxyapatite. For stones of mixed triamterene/calcium oxalate composition, the enhancement of the nucleation and crystallization of calcium oxalate was directly related to the calcium oxalate content of the stone seed material. The presence of soluble triamterene or its metabolites in solution did not influence the crystallization kinetics of pure calcium oxalate seed materials. The results of this study indicate that triamterene in stones does not significantly contribute to further stone development through the enhancement of calcium oxalate crystallization processes. PMID- 3105838 TI - Osteochondroma induced by reflection of the perichondrial ring in young rat radii. AB - In order to investigate the effects of reflection of the perichondrial ring in osteochondroma formation, the perichondrial rings of the epiphyseal growth plates in 42 young rat radii were turned to the metaphyseal periosteum by means of blunt dissection. Seven days after surgery a small nest of chondrocytes appeared on the metaphyseal-diaphyseal bone surface at the level of the tip of the reflected perichondrial ring. From the 9th to the 15th days the histological pattern of the osteochondroma was established. The osteochondroma was not connected with the hypertrophic cartilage of the growth plate. During the third and fourth weeks the osteochondroma began to regress with the disappearance of the cartilage nest. During the development of the lesion the bone grew normally and the growth plate migrated distally while the lesion remained at its initial site. The growth plate zone devoid of perichondrial ring was covered by fibrous connective tissue and no removal of the perichondrial ring occurred. These results suggest that the origin of this osteochondroma is the perichondrial ring cells whose polarity has been surgically changed. PMID- 3105839 TI - Effects of unilateral arterial infusion of GH and IGF-I on tibial longitudinal bone growth in hypophysectomized rats. AB - We have studied the effect of local arterial infusion of bacterially produced human growth hormone (hGH), insulinlike growth factor I (IGF-I), or pituitary derived ovine prolactin (oPRL) on longitudinal bone growth of hypophysectomized rats. The substances were infused during a 14-day period by osmotic mini-pumps through a catheter which was implanted into the femoral artery of one hindlimb. Longitudinal bone growth was measured by the intravital marker tetracycline. Infusion of 1 microgram hGH per day stimulated bone growth only of the treated limb and not of the uninfused contralateral limb. Infusion of 10 micrograms hGH per day also stimulated unilateral longitudinal bone growth, but the uninfused contralateral limb also showed a significant growth response, probably because local administration of GH at this dose caused a significant elevation of GH in the systemic circulation. As a result, the differential growth response between the GH-treated and untreated limbs decreased compared to rats that were infused with 1 microgram hGH per day. Unilateral arterial infusion of 5 micrograms human IGF-I or 10 micrograms oPRL per day did not produce a significant growth response. The results of the present study confirm the observation by Schlechter and co-workers, who demonstrated that unilateral arterial infusion of GH maintained tibial cartilage width following hypophysectomy in the rat. The results of Schlechter and coworkers and the results of the present study show that GH in vivo stimulates epiphyseal cartilage growth directly. However, an increased local production of insulinlike growth factors is probably of importance for the expression of the direct effect of GH on longitudinal bone growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105840 TI - Bovine dentin phosphophoryn: calcium ion binding properties of a high molecular weight preparation. AB - The calcium ion binding properties of a high molecular weight bovine phosphophoryn preparation have been studied at high ionic strength (0.5 M KCl as supporting electrolyte). Surprisingly, even under these conditions at which intermolecular ionic interactions are effectively screened, phosphophoryn was capable of binding calcium ions. This suggests that calcium ion binding by bovine phosphophoryn involves formation of a coordination complex or chelation. Two classes of binding sites were identified. The high affinity sites have a relatively low affinity constant of approximately 775 moles but maximally represented about 90% of the (SerP + Asp) residues along the polypeptide backbone. Binding was nonideal in that the number of high affinity sites showed a marked dependence on phosphophoryn concentration, increasing with the protein concentration. This unusual concentration dependence suggests that calcium mediated intramolecular interactions may limit available high affinity sites at lower phosphophoryn solution concentrations by a requirement for intramolecular folding. In support of this conclusion, the reduced viscosity of dilute phosphophoryn solutions was found to fall rapidly as a result of intramolecular folding, whereas at higher phosphophoryn concentrations calcium-mediated intermolecular aggregate formation slowed the rate of viscosity decrease. At the lower physiological ionic strength the affinity constant for specific calcium ion binding is several orders of magnitude greater than under the extreme conditions described in this work. PMID- 3105842 TI - Inhibition of calcium phosphate precipitation by human salivary acidic proline rich proteins: structure-activity relationships. AB - Absence of precipitation of calcium phosphate salts onto tooth surfaces from human saliva, which is supersaturated with respect to calcium phosphate salts, has been attributed in part to the presence in the salivary secretions of a group of acidic proline-rich phosphoproteins (PRP). These macromolecules are considered to act by adsorbing onto dental enamel where they inhibit surface-induced precipitation of calcium phosphate salts. The inhibitory activity is known to be associated primarily with the amino-terminal region of the PRP. The aim of this study was to determine the features of the primary structure of this molecular segment responsible for inhibitory activity. The 30-residue, amino-terminal segment of PRP-3, which contains the two phosphoserines and 11 of the 13 carboxyl groups present in PRP-3, was obtained by tryptic digestion. This peptide, designated PRP-3(TI), was treated with thermolysin to give the monophosphopeptides, Val-PSer-Gln-Glu-Asp-Val-Pro and Leu-Val-Ile-Ser-Asp-Gly-Gly Asp-PSer-Glu-Gln, and with alkaline phosphatase to give the dephosphorylated analog, PRP-3(TI)DP. The inhibitory activities of PRP-3(TI) and the derived peptides, a synthetic peptide, phosphoseryl-phosphoserine (PSer-PSer), and O phosphoserine (PSer), were determined using an assay based on inhibition of seeded precipitation of calcium phosphate. Inhibitory activities, expressed as concentrations of inhibitors required to give standard inhibitory activities, were PRP-3(TI), 0.59 microM; PSer-PSer, 3.5 microM; the two monophosphopeptides, 29 and 32.5 microM; PRP-3(TI)DP, 56 microM; PSer, 329 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105841 TI - Influence of nutritional factors on calcium-regulating hormones and bone loss. AB - The relationships between nutritional factors, calcium regulating hormones, and bone density were evaluated in three groups of normal subjects in rural southeast Kansas. Dietary intake of calcium (Ca), phosphorous (P), protein, and vitamin D; and serum 25OHD, Ca, P, parathyroid hormone (iPTH), and bone density (distal 1/3 radius) were measured in 29 elderly women, 35 elderly men, and 50 perimenopausal women. Measurements were repeated 5 years and 4 years later respectively in 16 elderly women and 15 elderly men. The r values for significant regression correlations for each group were as follows: perimenopausal: bone density and dietary Ca:P--r = .29, iPTH and 25OHD--r = -.38; elderly women: 25OHD and dietary Vitamin D(D)--r = .58, change in bone density (delta BD) and initial bone density (BDI)--r = -.71, delta BD and serum 25OHD--r = -.60, serum calcium and age--r = .42; elderly men: Serum 25OHD and D--r = .61, iPTH and 25OHD--r = -.43, iPTH and serum phosphorous--r = .59. CONCLUSIONS: The more adequate the state of vitamin D nutriture, the lower the serum iPTH in perimenopausal women and elderly men and the less bone loss in elderly women. The Ca:P ratio in the diet may be important in maintaining bone density in perimenopausal women. PMID- 3105843 TI - The effect of an oral calcium load on plasma ionized calcium and parathyroid hormone concentrations in osteoporotic postmenopausal women. AB - Plasma ionized calcium (IC) and parathyroid hormone (PTH) concentrations were measured in 31 osteoporotic postmenopausal women at hourly intervals for 5 hours after a 1 g oral calcium load. Fifteen subjects had normal radiocalcium absorption and 16 subjects were malabsorbers of calcium. IC rose and PTH fell after the calcium load in both groups with a plateau at 3-4 hours, and the rise in IC was greater (P less than 0.01) in the normal absorbers. There was a nonsignificant trend for the fall in PTH to be greater in the normal absorbers. In the group as a whole the mean increase in IC (above baseline) at 4 hours was directly related to calcium absorption (P less than 0.025) and the mean change in PTH was inversely related to calcium absorption (P less than 0.05). These results demonstrate that in subjects with postmenopausal osteoporosis the responses of IC and PTH to an oral calcium load are a function of calcium absorptive status. PMID- 3105844 TI - Temporal relationship between fetal bovine skeletal growth and circulating hormonal levels. AB - Skeletal growth and serum hormonal levels in bovine fetuses were studied cross sectionally from late first trimester to late third trimester of gestation (corresponding approximately to 75-275 days of age, and a crown-rump (CR) 5-105 cm/in size). Measurements of tibial and femoral lengths showed that bone growth proceeds at a 30% faster rate in fetuses of 50-105 cm CR, coincident with the appearance and exponential growth (y = 0.000207 e 0.12522 x; y, dried weights of ossification in grams and x, CR in cm) of a secondary center of ossification in the epiphysis. During this period there is an increase in the proportion of [3H] thymidine-labeled nuclei (measured by autoradiography) in the proliferative zone of the epiphyseal growth plate and a progressive hypertrophy of chondrocytes in the epiphysis; in serum there is a rise in alkaline phosphatase activity, a rise in the calcium, and a decrease in the phosphorus concentrations. Cellularity (nuclei/area) and the proportion of [3H]-thymidine labeled nuclei in epiphyseal cartilage decline during the period of 15-105 cm CR, except at 25-45 cm CR when both parameters of chondrocyte growth have transiently stabilized. [35S]-Sulfate and [3H]-proline incorporation (cpm/100 micrograms DNA) in epiphyseal cartilage also decline initially during 10-25 cm CR, then attain a stable level during 25 50 cm CR; subsequently, [35S]-sulfate incorporation gradually increases and [3H] proline incorporation remains at a constant level. The proportion of [3H] thymidine-labeled nuclei in the epiphyseal growth plate also declines in early gestation, then becomes stabilized at 20-50 cm CR. The whole growth plate thickness varies during gestation and is maximal during 20-50 cm CR. The proliferative zone attains maximal thickness at 20-50 cm CR while the hypertrophied and degenerative zone has maximal thickness at 40-80 cm CR. Gestational changes of hormone levels were quantitated in fetal serum. Glucocorticoids and thyroxine were measured by radioimmunoassay; somatomedinlike bioactivity was measured as the capacity of a serum sample to stimulate [3H] thymidine incorporation in chondrocytes compared to that of a control serum. Temporally related to the changes occurring in the skeletal tissues, there is a high serum level of glucocorticoids at 10-20 cm CR when the cartilaginous activities are declining, a peak level of serum somatomedinlike bioactivity at 20 50 cm CR when cartilage growth and metabolism become stabilized, and a rise of thyroxine level after 45 cm CR during which time there is an increasing rate of bone formation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3105845 TI - Calcitonin gene-related peptide inhibits osteoclastic bone resorption: a comparative study. AB - Besides the calcitonin (CT) precursor, the calcitonin gene also encodes another peptide--calcitonin gene-related peptide (CGRP). We have previously reported that CGRP lowers plasma calcium in the rat. In the present study we have evaluated the effect of CGRP on resorption of bone by isolated rat osteoclasts and have compared these effects to those produced by calcitonins from three species (salmon, pig, and human calcitonins). There was a significant inhibition of bone resorption with rat calcitonin gene-related peptide (rCGRP) at a 1000-fold higher dose than that used for human CT. This effect well explains the CT-like effect of CGRP seen in the in vivo rat CT bioassay. Our results suggest that though CGRP may not be involved in the hormonal control of plasma calcium, the peptide may be an important local regulator of bone cell function. PMID- 3105846 TI - Effect of body weight on osteopenia in ovariectomized rats. AB - Bilateral ovariectomies or sham surgeries were performed in female Sprague Dawley rats that were 78 days of age and weighed an average of 210 g. Food was available ad libitum to the control rats and to a group of ovariectomized rats (obese OVX). The food consumption of a second group of ovariectomized rats (weight-matched OVX) was restricted to match their body weights to those of the control rats. All rats were sacrificed at 14 weeks postovariectomy. Radioimmunoassay of terminal serum estradiol confirmed the success of ovariectomy. The estradiol concentration in control rats was 24.9 +/- 20.2 pg/ml, whereas the hormone was undetectable (less than 10 pg/ml) in both groups of OVX rats. The final body weights of control and weight-matched OVX rats were nearly identical (approximately 260 g). In contrast, obese OVX rats weighed significantly more than both of the above groups (approximately 320 g, P less than 0.001). The proximal tibia and lumbar vertebra were processed undecalcified for quantitative bone histomorphometry. Tibial trabecular bone volume (TBV) was determined to be 17.6 +/- 4.5%, 7.9 +/- 5.3%, and 3.6 +/- 3.1% for the control, obese OVX, and weight-matched OVX groups, respectively. Tibial TBV for both OVX groups was significantly less than the control value (P less than 0.001). The difference in tibial TBV between obese OVX and weight-matched OVX rats was also statistically significant (P less than 0.02). Histologic indices of bone resorption and formation were indicative of increased bone turnover in the proximal tibia of both OVX groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105847 TI - Different schedules of administration of (3 amino-1-hydroxypropylidene)-1, 1 bisphosphonate induce different changes in pig bone remodeling. AB - Intermittent administration of antiosteoclastic agents has been proposed in order to increase trabecular bone volume (TBV). We evaluated the effect of two different intermittent schedules of administration of (3 amino-1 hydroxypropylidene)-1, 1 bisphosphonate (AHPrBP) on pig bone remodeling for a period of 60 days. AHPrBP (1.6 mumol/kg/injection) was given subcutaneously daily (group A1), or 5 consecutive days out of 21 days (group A2), or 1 out of every fourth day (group A3). Compared to control animals, group A1 significantly increased trabecular bone volume (TBV) (+62%) with a marked decrease in bone resorption assessed by interstitial bone thickness. Bone formation assessed by mean wall thickness (MWT) was also decreased due to a decrease in the number and activity of osteoblasts. There was not a delay in the coupling mechanism as assessed by the reversal surfaces. The two groups receiving intermittent schedules had markedly different results. Group A2 had very similar changes to group A1 despite receiving four time less drug. Compared to group A1 and A2, group A3 had smaller decrease in resorption and higher bone formation rate with identical MWT. These differences between group A2 and A3 were associated with similar levels of parathyroid hormone and vitamin D metabolites. Different bone concentrations induced by the two different schedules of AHPrBP may explain the greater effect on bone resorption and osteoblast recruitment in group A2 and thus a milder effect of the AHPrBP administration once every fourth day. PMID- 3105848 TI - The dichotomy in the effects of 1,25 dihydroxyvitamin D3 and 24,25 dihydroxyvitamin D3 on bone gamma-carboxyglutamic acid-containing protein in serum and bone in vitamin D-deficient rats. AB - Vitamin D-deficient, second generation, rachitic rats showed significant decrease in bone Gla protein (BGP) levels in circulation and in the skeleton. 1,25 dehydroxyvitamin D3 (1,25(OH)2D3) exhibited the most potent influence on serum BGP levels in a dose-dependent manner. At a dose 25 ng/100 g body weight 1,25(OH)2D3 showed a cumulative effect, i.e., the longer the treatment, the more circulating BGP was detected. 24,25 dehydroxyvitamin D3 (24,25(OH)2D3) at the same doses did not show similar effect on the serum BGP levels, regardless of the serum calcium levels. Bone BGP levels assayed at various sites representing endochondral and intramembranous ossification demonstrated an opposite pattern. 1,25(OH)2D3 administration was not sufficient to restore bone BGP levels to normalcy, whereas in animals treated with 24,25(OH)2D3, bone BGP and calcium levels were significantly higher than control (Vitamin D3-repleted) levels. The present results can be explained by the dual action of 1,25(OH)2D3 on both synthesis and release of BGP by bone turnover, whereas 24,25(OH)2D3 stimulates synthesis and accumulation of BGP in bone. These observations imply that caution is required in the interpretation of clinical data based solely on serum BGP determination. PMID- 3105849 TI - Endocytosis is required for the mitogenic effect of basic calcium phosphate crystals in fibroblasts. AB - Basic calcium phosphate (BCP) crystals stimulate mitosis of cultured fibroblasts and synoviocytes in vitro. Although intimate crystal-cell contact is required for mitogenesis, and lysosomotropic agents such as chloroquine and ammonium chloride block the mitogenic effect of crystals, the requirement of endocytosis has not been demonstrated. Synthetic BCP crystals, uniformly trace-labeled with 45Ca, were added to cultured, quiescent, confluent human foreskin fibroblasts in the presence or absence of ammonium chloride. After 4 or 24 hours, cultures were pulsed with 3H thymidine. The cells were then released with EDTA and trypsin, and fractionated on preformed Percoll density gradients. Fractions were analyzed for incorporation of 45Ca and [3H]thymidine and cell number. The cells containing 45Ca crystals also were heavily labeled with thymidine. Ammonium chloride decreased the amount of crystals endocytosed, and inhibited mitogenesis. These data suggest that mitogenesis induced by BCP crystals is preceded by endocytosis and dissolution in the acidic environment of phagolysosomes. PMID- 3105851 TI - Carbonic anhydrase III inhibition in normocapnic and hypercapnic contracting mouse soleus. AB - The physiological role of carbonic anhydrase III in slow-twitch skeletal muscle was investigated using isolated mouse soleus (N = 30) contracting once every 1.7 min for 75 min in Krebs-Henseleit solution gassed with either 95% oxygen - 5% carbon dioxide (normocapnia) or 90% oxygen - 10% carbon dioxide (hypercapnia). Each contraction was 500 ms in duration at 50 Hz. When muscles contracted in normocapnic solution (pH 7.42), the developed tension decreased an average of 6.1 +/- 0.8% over 25 min. For the next 50 min, 15 muscles remained normocapnic, while the remainder contracted in hypercapnic solution (pH 7.20). Tension decreased significantly more with hypercapnia. For the last 25 min, both normocapnic and hypercapnic muscles were divided into three treatment groups (N = 5). One group continued in the same environment, while acetazolamide (final concentration of 10(-5) M) was added to the bath of the second and sodium cyanate (final concentration of 10(-5) M) was added to the bath of the third group. Acetazolamide had no effect on tension in either carbon dioxide environment. Sodium cyanate significantly decreased tension from the hypercapnic control but had no effect in normocapnia. Thus carbonic anhydrase III inhibition with sodium cyanate increased the effect of hypercapnia implying that carbonic anhydrase III assists in the regulation of free hydrogen ion concentration in slow-twitch skeletal muscle. PMID- 3105850 TI - Hemodynamic and electrophysiologic effects of encainide in patients with bundle branch block. AB - Electrophysiologic studies were performed in 6 consecutive patients with bundle branch block and organic heart disease. All were studied after intravenous (0.9 mg/kg) encainide and 3 of the 6 after 36-72 hours of oral encainide (50 mg every 6 hours). After intravenous encainide, mean H-Q increased from 51 +/- 20 msec to 58 +/- 25 msec (14% p less than or equal to .05). After oral encainide (3 patients) H-Q increased to 90 +/- 39 msec (56% p less than or equal to .05, compared to baseline). Programmed ventricular stimulation was performed in 5. In 1 patient without spontaneous ventricular tachycardia, tachycardia was non inducible before and after encainide. Of 5 patients with spontaneous arrhythmia, 3 had ventricular tachycardia induced before and after intravenous encainide at mean cycle lengths of 287 +/- 130 msec and 407 +/- 261 msec, (not significant) respectively, while 1 had ventricular tachycardia induced only after encainide. Four patients began chronic treatment with oral encainide (2 patients with inducible rapid ventricular tachycardia after encainide were excluded). All suffered major adverse outcomes. One died suddenly after an electrophysiology study demonstrated inducible ventricular tachycardia, which occurred only after encainide. One experienced new syncope after baseline H-Q increased 75% after encainide. Two patients developed new sustained atrial tachycardias and 1 patient developed persistent ventricular tachycardia on encainide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105852 TI - Effects of cold storage on relaxation responses in the rat oesophageal tunica muscularis mucosae. AB - Tetrodotoxin-resistant relaxations produced by electrical field stimulation, 5 hydroxytryptamine (5-HT), and A23187 (calimycin) were investigated in the rat isolated oesophageal tunica muscularis mucosae subjected to cold storage of varied duration. Cold storage for 2 days abolished cholinergic nerve mediated contractions to field stimulation; however, field stimulation evoked relaxations and muscarinic agonist evoked contractions persisted undiminished. After 5 days of cold storage, field-stimulated relaxations, as well as tension generating capacity of the tissue, were significantly reduced. Proximodistal differences were observed in tunica muscularis mucosae sensitivity to the relaxant effects of serotonin and A23187 and these were exaggerated after cold storage. In the distal segment, cold storage for 2 days unmasked ketanserin-sensitive 5-HT receptors mediating contractions. Similarly, A23187 induced contractions rather than relaxation in cold-stored distal tunica muscularis mucosae; however, this effect was resistant to ketanserin. Immunohistochemical staining by means of the peroxidase-antiperoxidase technique revealed 5-HT-like immunoreactive "mast cells" within the tunica muscularis mucosae. These cells appeared to be associated with the smooth muscle rather than the vasculature. It is concluded that field-stimulated relaxation is not dependent on intramural nerves, and it is unlikely that the release of 5-HT from mast cells or other cells mediates field stimulated relaxation. However, confirmation awaits the provision of an antagonist against the novel 5-HT receptor that mediates 5-HT-induced relaxations. PMID- 3105853 TI - Effect of cyclooxygenase and thromboxane synthetase inhibition on furosemide stimulated plasma renin activity. AB - We studied the effects of a specific thromboxane (TX) synthetase inhibitor (U 63,557A) and a cyclooxygenase inhibitor on furosemide-induced renin release. Furosemide (2.0 mg X kg-1) was injected into Sprague-Dawley rats pretreated with indomethacin (10 mg X kg-1, i.v.), U-63,557A (1.0-32.0 mg X kg-1, i.v.), or vehicle (Na2CO3 0.03 M). Plasma renin activity was measured in blood samples collected 0, 10, 20, and 40 min after the injection of furosemide. Blood was also collected after the administration of vehicle, indomethacin, or U-63,557A for serum TXB2, a measure of platelet TXA2 synthesis. The results demonstrated that plasma renin activity rose with time following furosemide in the various groups of rats; indomethacin suppressed the furosemide-induced increments in plasma renin activity, while U-63,557A at doses of 4-8 mg X kg-1 augmented it. At doses below 4 mg X kg-1 or above 8 mg X kg-1, U-63,557A did not augment renin secretion. Indomethacin and U-63,557A reduced serum thromboxane by 81 and 90%, respectively. Thus, these experiments suggest that thromboxane synthetase inhibition, within a narrow dosage range, potentiates furosemide-induced renin release while cyclooxygenase inhibition suppresses it. PMID- 3105854 TI - Comparative study suggests greater care necessary in selecting absorbable sutures in surgical closings. PMID- 3105855 TI - Interbacterial adhesion between Pseudomonas aeruginosa and indigenous oral bacteria isolated from patients with cystic fibrosis. AB - Interbacterial adhesion between strains of Pseudomonas aeruginosa and strains of indigenous oral bacteria, both of which were isolated from the oral cavity of cystic fibrosis patients, was investigated by the phenomenon of the coaggregation reaction. A total of 22 strains of P. aeruginosa were isolated from the oral cavity of 17 patients and examined for their abilities to coaggregate with 5 strains each of Streptococcus sanguis, Streptococcus mitis, Actinomyces viscosus, and Actinomyces naeslundii. Coaggregation reactions were common between these oral bacteria and both the mucoid and nonmucoid variants of P. aeruginosa. All strains of P. aeruginosa were also able to agglutinate neuraminidase-treated or untreated human erythrocytes of blood types A, B, and O. Positive coaggregation reactions were further characterized by determining the effects of several sugars, and of heat and protease treatments of the bacteria. None of the coaggregtion reactions were inhibited by 0.05 M lactose, galactose, glucose, fucose, or mannose. All coaggregation reactions were dependent upon heat- and protease-sensitive components of the Pseudomonas. Thus, the interbacterial adhesions between P. aeruginosa and the oral bacteria studied appears to involve adhesins on the Pseudomonas cell, which bind to complementary receptors, on the cell surfaces of oral bacteria. The apparent prevalence and diversity of interbacterial adhesions between P. aeruginosa strains originating from the oral cavity of cystic fibrosis patients and strains of the indigenous oral bacteria suggest that some of these reactions may affect the extent to which P. aeruginosa colonizes in the oral cavity of cystic fibrosis patients, and thereby, influence susceptibility of the host to infection. PMID- 3105856 TI - Analysis of microcalorimetric curves for bacterial identification. AB - A numeric method is suggested for the treatment of microcalorimetric curves of bacterial growth to provide a new tool for their automatic identification. In this method the microcalorimetric curves are searched against certain reference profiles (stored in a library) by means of a cross-correlation analysis and a parametric comparison. The matching between the new curve and each reference profile is evaluated by means of a specific identification coefficient which provides an objective criterion for the identification of each species. The reliability of the method is discussed. PMID- 3105857 TI - Characterization by pyocine typing and serotyping of oral and sputum strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients. AB - Oral and sputum isolates of Pseudomonas aeruginosa in patients with cystic fibrosis were investigated. Of the 17 patients studied, 12 patients (71%) yielded both mucoid and nonmucoid variants of Pseudomonas aeruginosa from sputum and (or) various oral ecological sites, such as buccal mucosa, tongue dorsum, dental plaques, and saliva. A total of 51 strains of mucoid and nonmucoid Pseudomonas aeruginosa were isolated from these patients and were phenotypically characterized by both pyocine typing and serotyping. Five patients (42%) were colonized or infected by a single strain of Pseudomonas aeruginosa, whereas 7 patients (58%) were cocolonized or coinfected by two or more phenotypically different strains of Pseudomonas aeruginosa. To understand the mechanisms involved in Pseudomonas aeruginosa colonization, it may be necessary to identify multiple isolates of Pseudomonas aeruginosa not only from the sputum but also from the various oral ecological sites and to further explore the role of the oral cavity in this colonization. PMID- 3105858 TI - The role of beta-lactamase and the permeability barrier on the activity of cephalosporins against members of the Bacteroides fragilis group. AB - The role of beta-lactamase and the permeability barrier on the activity of some beta-lactams against 53 strains of the Bacteroides fragilis group was investigated. Minimal inhibitory concentrations of cefamandole, cefoxitin, and cephalothin were determined with or without the addition of clavulanic acid and (or) ethylenediaminetetraacetate using an agar dilution technique. A significant increase of susceptibility with clavulanic acid indicated a role for beta lactamase, and with ethylenediaminetetraacetate, a role for a permeability barrier. We found that both beta-lactamase and low permeability decreased the activity of the beta-lactams to some extent depending on the bacterial species and the antibiotic. The species-specific exception was B. distasonis which showed only a permeability barrier to all antibiotics tested. PMID- 3105860 TI - Free T4 measurement is preferred to the T4 test for thyroid evaluation in lithium treated patients. AB - Free T4 (fT4) measurement provides a more sensitive test of thyroid function than the commonly used T4. Recent commercial development of fT4 kit assays has made fT4 assessment widely available. Evaluation of the fT4 Amerlex kit in 26 lithium treated patients illustrates its utility as a sensitive laboratory test of thyroid function in this group of patients. This finding together with fT4's known superiority over T4 in identifying thyroid dysfunction suggests that fT4 should replace T4 estimations in the routine monitoring of thyroid function in lithium-treated patients. PMID- 3105859 TI - Feasibility of chemical screening of urine for neuroblastoma case finding in infancy in Quebec. AB - Neuroblastoma is the most common fatal solid tumour of childhood. Studies in Japan suggest that screening urine at 6 months for tumour-derived metabolites greatly improves early case finding and prognosis. The incidence rate of neuroblastoma in Quebec is at least 1 per 10,330 live births, higher than that of all other diseases responding to early treatment except congenital hypothyroidism screened for in the Quebec Network of Genetic Medicine. The feasibility of chemical screening of urine for elevated levels of homovanillic acid and vanillylmandelic acid in Quebec was assessed. The cost-effectiveness of screening 100,000 infants per year would be high (cost-benefit ratio 2.4), with a net saving of about $280,000 and eight lives per year. The estimated cost of adding neuroblastoma screening to the existing urine metabolite screening program is $70,700. The apparent sensitivity of the proposed test is 0.859 and the rate of false-positive results about 0.1%, both acceptable values. The attitude of potential participants toward the present urine screening program and the addition of a "tumour test" was positive. The results indicate that a pilot study of neuroblastoma screening in Quebec could be undertaken. PMID- 3105861 TI - Mental changes associated with tocainide, a new antiarrhythmic. AB - A case is reported in which tocainide, a relatively new cardiac antiarrhythmic for oral use, is believed to have caused a delirium. The patient had been admitted to a coronary intensive care unit for the treatment of ventricular arrhythmia and had developed confusion, impairment in concentration and severe anxiety. Her EEG was compatible with metabolic encephalopathy. The clinical picture varied with the use of tocainide so closely that it appeared to be the most likely cause of the delirium. Other factors were taken into consideration but did not seem to adequately disprove this impression. Tocainide has been known to cause minor, transient and treatable side effects in the form of gastrointestinal and central nervous symptoms--mainly nausea, tremor and dizziness. There have also been three case reports of paranoid psychoses. It is suggested that psychiatrists be aware of the above complications as they may have occasion to see patients taking tocainide, especially in consultation-liaison work. A table with the more common side effects and their frequencies is included. PMID- 3105862 TI - Phase II study of hepatic arterial degradable starch microspheres and mitomycin. AB - Twenty four patients with incurable primary or metastatic liver cancer were treated with hepatic arterial Mitomycin C admixed with degradable starch microspheres (DSM). Six objective responses (25% PR) were obtained in this heavily pretreated population with advanced disease. The median response duration was 3.5 months. Hematologic toxicity was minimal as would be expected from the reduced systemic exposure generated by the increased regional drug deposition. An apparent chemical hepatic arteritis developed in five patients after multiple courses, however, its relationship to prior hepatic arterial infusion therapies, Mitomycin, starch microspheres, and repeated dosing of the drug-microsphere mixture remains unclear. The responses seen in this study are encouraging given the heavily pretreated population in which they were obtained. Studies delineating the relative contribution of DSM to both the response and the toxicities of hepatic arterial Mitomycin and other appropriate antineoplastic agents in the treatment of single tumor types are needed. PMID- 3105863 TI - Immunologic profile in patients with Hodgkin's disease in complete remission. AB - Mononuclear cell subsets in peripheral blood, in vitro production of interleukin 2 (IL-2) and gamma interferon (IFN gamma), spontaneous cell-mediated cytotoxicity (SCMC) and circulating levels of Type I IFN, neopterin, beta-2 microglobulin (B2 M), immunoglobulins and complement fractions were studied in 33 patients with Hodgkin's disease (HD) in complete remission. The mean percentages, but not the absolute numbers, of T-lymphocytes expressing pan-T markers (OKT11, OKT3, ER, E AET R) were significantly decreased compared with control values. Furthermore, patients showed a selective loss of OKT4+ cells, as well as increased percentages and numbers of Leu7+ and OKIa+ lymphocytes, and of OKM1+, LeuM2+, and LeuM3+ cells. OKT4+ cell depletion was a characteristic of patients with shorter time since beginning of remission as well as of those with nodular sclerosis (NS), mixed cellularity Hodgkin's disease (MC-HD), and systemic symptoms at diagnosis. Multifactorial statistical analysis carried out to investigate the effect of disease characteristics and the time since remission began on peripheral mononuclear blood cell (PMBC) subsets showed that histologic condition was the single best predictor of T-cell pool or OKT4+ cell subset size. Time since remission duration and other disease-related factors determined differences in the percentages, but not in the absolute numbers, of T-cell fractions. In addition, neither the disease features nor the time since remission duration determined significant differences in the absolute number of non-T-mononuclear cells in the various patient groups. Patients displayed decreased in vitro synthesis of IL-2 and IFN gamma. The values of SCMC, Type I IFN, neopterin, B2-M, immunoglobulins, and complement fractions did not differ greatly from those of controls. PMID- 3105864 TI - Differences between the F10, BL6 and F1 sublines of the B16 melanoma in the enhancement of plasminogen activator and plasminogen activator inhibitor secretion by phorbol myristate acetate. AB - Analysis of conditioned medium from three sublines of the B16 melanoma [F1 (parental), BL6 (invasive), F10 (metastatic)] by SDS-PAGE and zymography revealed the presence of plasminogen activator activity at 60,000 daltons. The relative activity was F10 greater than F1 greater than or equal to BL6. Treatment of the cells with the tumor promoter, phorbol myristate acetate (PMA) led to increased secretion of PA by F10 cells and a lesser increase in secretion by F1 cells and BL6 cells. In addition, a second plasminogen activator activity at 45,000 daltons was detected in conditioned medium from PMA treated F10 cells. Conditioned medium from F10 and F1 cells was also shown to contain a 33,000 dalton plasminogen activator binding protein. Upon PMA treatment the concentration of the binding protein increased in medium from F10 cells but not in similarly treated F1 cells. The binding protein, very likely a plasminogen activator inhibitor, was nearly undetectable in conditioned medium from control and PMA-treated BL6 cells. Therefore, the three sublines, which differ in in vivo phenotypic characteristics, also differ in their in vitro regulation of proteinase and proteinase inhibitor synthesis. PMID- 3105866 TI - Quantitation of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene binding to nuclear macromolecules in human and rat mammary epithelial cells. AB - Our laboratory has developed virtually identical techniques for the isolation and culture of mammary epithelial cells (MEC) from rats and humans. In a cell mediated mutagenesis assay, rat MEC activated 7,12-dimethylbenz(a)anthracene (DMBA) but not benzo(a)pyrene [B(a)P] to mutagenic forms, and the opposite pattern was found with human MEC. These species-specific patterns were not readily explained by either qualitative or quantitative differences in Phase I metabolism of these compounds. In contrast, relative levels of covalent binding of these compounds to DNA in the human and rat cells under identical assay conditions generally parallel the pattern of the mutagenesis results, while not reflecting the absolute levels of metabolism in each system. The ability of the rat MEC to bind relatively higher levels of DMBA than B(a)P to nuclear DNA, and the reversed pattern in human MEC, was found at all incubation times tested between 6 and 48 h. Culture density was found to exert a greater effect on the levels of PAH-DNA binding in rat than in human cells, but in neither case did it affect the ratio of DMBA to B(a)P binding within a species. C2SO4 gradient separation of nuclear macromolecules from PAH-treated MEC revealed that the relative DNA binding levels of DMBA and B(a)P did not correlate with relative levels of nuclear protein binding. For both species, nuclear (DNA + protein) binding levels of B(a)P were approximately 2-fold higher than DMBA. However, these binding levels were 4 to 5-fold higher for both carcinogens in the human than in the rat MEC. The species-specific patterns of PAH activation shown by these cells suggest that caution should be used in extrapolating rodent carcinogenesis data to humans, for either quantitative or qualitative purposes. PMID- 3105865 TI - Immunomodulatory and immunotherapeutic properties of recombinant gamma-interferon and recombinant tumor necrosis factor in mice. AB - These studies were designed to examine the immunodulatory and immunotherapeutic properties of recombinant murine interferon gamma (rM IFN-gamma) and recombinant human tumor necrosis factor (rH TNF). We report that rM IFN-gamma activated murine natural killer cells and macrophages in a dose-dependent manner in vivo. The rM IFN-gamma, which demonstrated a bell-shaped therapeutic response curve, must be administered at specific doses and schedules to produce optimal therapeutic activity. Optimal activity was observed after i.v. administration of 50,000 U/animal rM IFN-gamma three times per week. In contrast, rH TNF produced its major therapeutic activity in the treatment of metastatic disease after i.v. but not i.p. administration. The therapeutic effects of rH TNF were as great in these in vivo systems as those of rM IFN-gamma. Furthermore, rH TNF had additive therapeutic activity when administered in conjunction with suboptimal doses of rM IFN-gamma. Unlike rM IFN-gamma, rH TNF did not activate natural killer cells in vivo or in vitro but did augment in vivo and in vitro macrophage tumoricidal activity. It also had synergistic cytostatic properties with rM IFN-gamma for some murine tumor cell lines in vitro. High levels of rH TNF were readily detected in the serum with a half-life of approximately 30 min after i.v. administration. In contrast, only minimal serum TNF activity occurred after i.p. administration, suggesting that i.v. administration may more efficiently facilitate systemic therapeutic activity. In summary, rH TNF and rM IFN-gamma have therapeutic activity for metastatic disease as individual agents and additive therapeutic activity when used in combination. Furthermore, it appears that in addition to therapeutic potential as cytostatic agents, the immunomodulatory properties of rH TNF have a role in its therapeutic properties. PMID- 3105867 TI - Synergistic antitumor effects of tumor necrosis factor and gamma-interferon on human colon carcinoma cell lines. AB - We assessed the antiproliferative effects of tumor necrosis factor (TNF-alpha) and gamma-interferon (IFN-gamma) alone and in combination, on nine human colon carcinoma cell lines. All were resistant (less than 30% inhibition) to TNF-alpha alone. Four cell lines were resistant to IFN-gamma alone, two exhibited a minimal degree of sensitivity (30-50% inhibition), one was moderately sensitive, and two were inhibited 70% or greater. A synergistic antiproliferative effect occurred in eight of the nine cell lines treated with a combination of TNF-alpha and IFN gamma. In seven of these eight, the combination of cytokines resulted in 30-40% more growth inhibition than predicted had an additive interaction occurred (P less than 0.005). In two cell lines with an induced resistance to mitomycin C, an increase in resistance to combined TNF-alpha and IFN-gamma treatment correlated with an increasing resistance to mitomycin C. The data were further analyzed to determine if combination treatment altered the sensitivity of the cells to one or both agents in addition to synergistically potentiating growth inhibitory effects. Combinations of TNF-alpha/IFN-gamma enhanced the dose response activity of TNF-alpha in three cell lines (P less than or equal to 0.09) and decreased the dose response activity of IFN-gamma in another three (P less than or equal to 0.02). Colony forming experiments on HCT 116 cells demonstrated a reduction in the number of 250-micron colonies in the IFN-gamma/TNF-alpha treatment groups when compared to controls, indicating that combined treatment had a cytotoxic effect. We conclude that combination TNF-alpha/IFN-gamma treatment has a synergistic cytotoxic effect on human colon carcinoma cells. IFN-gamma may enhance the effectiveness of TNF-alpha in some cell lines, but not conversely. These results may have therapeutic implications. PMID- 3105868 TI - Modification of Ha-ras oncogene p21 expression and cell cycle progression in the human colonic cancer cell line HT-29. AB - Multiparameter flow cytometric measurements of the Ha-ras oncogene product, Ha p21, versus DNA content were used to study the effect of prednisolone, sodium butyrate, and hyperosmolality on the expression of this gene during the cell cycle of HT-29, a human colonic carcinoma cell line. In control cells the expression of Ha-p21 was cell cycle dependent; it increased during G1 and remained approximately constant as cells traversed the S- and G2 + M phases. Two compartments of G1 cells, one expressing low (G1A) and the other (G1B) high levels of Ha-p21 could be identified. Cells grown with prednisolone (1.4-2.1 microM) expressed higher Ha-p21 levels than controls. Cell cycle analysis revealed that this effect was accompanied by a change in the distribution of cells in G1 phase: whereas the proportion of cells in G1A was reduced, that of cells in G1B was increased. The steroid had no detectable effect on cells in S and G2 + M. By contrast, sodium butyrate and hyperosmolality caused a marked decrease in Ha-p21 content. This reduction was not accompanied by any modification of the proportion of cells in the cell cycle compartments. These results would suggest that Ha-p21 is not likely to be a primary regulator of cell cycle progression in HT-29 cells. PMID- 3105869 TI - Estrogen receptor binding to nuclei from normal and neoplastic rat mammary tissues in vitro. AB - To investigate the role of hormones in regulating growth of neoplastic mammary cells, we established a heterologous assay for studying interactions of partially purified calf uterine [3H]estradiol-charged estrogen receptor ([3H]ER) with rat tumor nuclei in vitro. This system displays saturable high affinity binding of [3H]ER which is time and salt dependent. Optimal assay conditions required for the heterologous system were identical to those we reported for the homologous calf nuclear binding system. Specificity of [3H]ER binding was demonstrated; 10 fold excess unlabeled estrogen-charged ER (EcR) competed for greater than 90% of the [3H]ER binding sites and binding of [3H]estradiol (not complexed with ER) was less than 1% of [3H]ER binding. Binding of [3H]ER displayed tissue specificity in decreasing order: R3230AC mammary tumor greater than lactating mammary gland = liver greater than kidney greater than lung. Scatchard analysis of saturation data provided estimates of binding affinity to nuclei from R3230AC mammary tumors [Kd, 2.0 +/- 0.3 (SE) nM); the number of binding sites per nucleus for R3230AC tumors was 95,000 +/- 13,800. [3H]ER binding to nuclei isolated from R3230AC rat mammary tumors grown in intact rats was 40% higher than that observed in tumors from ovariectomized animals. Results of administration of individual pharmacological doses of either progesterone or an estrogen to ovariectomized rats did not restore nuclear ER binding levels in R3230AC tumors to those detected in tumors from intact rats. These results suggest that the physiological levels of endogenous hormones produced by the ovaries are important in regulating the number of ER binding sites in nuclei from these mammary tumors. PMID- 3105870 TI - Establishment of a human B-cell tumor in athymic mice. AB - Human B-cell tumors have been established in athymic, BALB/c mice using the EBV positive Burkitt lymphoma cell line Namalwa. One-hundred-one of 104 animals (97%) developed tumors 10-14 days following s.c. injection of a mixture of 20 x 10(6) Namalwa and 5 X 10(6) irradiated human fibrosarcoma (HT-1080) cells. Tumors developed at the site of injection and reached approximately 300 mm2 (product of cross-sectional diameters) after 21 days; no metastases were found. Histological analysis showed that tumors consisted solely of lymphoid cells. Immunofluorescence assays demonstrated that while 85% of the tumor cells retained reactivity with the monoclonal B-cell antibody BA-1, 96% retained reactivity with antibody BA-2 and 43% with BA-3. A similar reactivity profile was observed with cultured Namalwa cells. Tumors were passaged serially 10 times without significant change in BA-1, BA-2, or BA-3 reactivity. Indirect immunofluorescence demonstrated that antibody BA-2 reached tumor cells within 2 h following i.p. injection; antigen modulation was not observed. These results demonstrate the suitability of this B-cell model for testing the in vivo efficacy and stability of anti-B-cell immunoconjugates. PMID- 3105871 TI - Association of colorectal tumor epithelium expressing HLA-D/DR with CD8-positive T-cells and mononuclear phagocytes. AB - Forty-eight human colorectal adenocarcinomas, removed at different stages of development, have been examined immunohistochemically for the expression of class II molecules and for the relationship of such class II expression to infiltrating leukocytes. Forty-four% of tumor epithelium samples express class II molecules. This expression is confined to the proteins coded for by the HLA-D/DR subregion although the surrounding infiltrating cells express HLA-D/DR, -DQ, and -DP coded proteins. In addition, there are significantly greater numbers of mononuclear phagocytes and T-cells of the CD8 antibody-positive subset associated with the tumors expressing class II molecules on tumor epithelium compared to the class II negative tumors. The T-cells appear not to be activated judging by the lack of expression of the receptor for interleukin-2 but the mononuclear phagocytes express CR1, the receptor for the complement component C3b, which suggests that they are stimulated. PMID- 3105872 TI - Rationale and strategies for chemoprevention of cancer in humans. AB - The potential for chemical intervention (chemoprevention) as a means of halting or delaying the process of carcinogenesis is assessed as a strategy for reducing the incidence of human cancer. The process of carcinogenesis is dissected into its constituent steps, thereby exposing sites for intervention. These sites are then critically discussed with regard to the existence of chemicals active at these sites using data gained from the laboratory and from epidemiological studies, intrinsic problems or advantages associated with intervention at specific sites in the carcinogenic process, and practical aspects of intervention in humans. The design and potential long-term positive and negative consequences of chemoprevention clinical trials are critically discussed, with the objective of exposing the major differences that exist between clinical trials in cancer chemoprevention and those in cancer chemotherapy. Results of completed prevention trials and details of ongoing trials are presented and discussed. Based on the laboratory, epidemiological, and clinical evidence presented, it is concluded that chemoprevention offers excellent prospects as a means of reducing cancer incidence. Among currently available agents, the retinoids possess the best combination of properties. However, much more research is needed to optimize drugs and protocols and to develop interim end points for assessing response. The authors finally caution that overambitious claims for the prospects for chemoprevention may lead to reduced emphasis on the need for changes in life style (principally in smoking and diet) that are viewed as having the greatest potential for reducing cancer incidence. PMID- 3105873 TI - Schedule-dependent interaction of alpha-difluoromethylornithine and cis diamminedichloroplatinum(II) against human and hamster pancreatic cancer cell lines. AB - The interaction of cis-diamminedichloroplatinum (cisplatin) and alpha difluoromethylornithine (DFMO) has been previously shown by us to be roughly additive in enhancing the growth-inhibitory effects of cisplatin and by another group of investigators to be antagonistic. Since two different schedules of administration were used, we sought to investigate systematically the role of schedule dependence in the interaction of cisplatin and DFMO in a panel of pancreatic adenocarcinoma cell lines (PANC-1, of human origin, and WD PaCa and PD PaCa, both of hamster origin). Dose-effect relationships of single drug alone and in combination were analyzed by the median-effect principle and by the combination indices for the quantitation of synergism or antagonism with the aid of a microcomputer. Pre-cisplatin administration of DFMO for 2 or 5 to 6 days at concentrations of 50 or 100 micrograms/ml (0.21 or 0.42 mM) was found to antagonize the effects of cisplatin to various degrees in the cell lines. In contrast, whenever post-cisplatin DFMO was administered, marked enhancement, which was synergistic in most instances, of cisplatin's inhibition of colony formation was found. Thus, the interaction of cisplatin and DFMO is felt to be schedule dependent with deleterious effects found only when DFMO is administered prior to and not following cisplatin. Furthermore, the combination shows promise as an approach to overcoming drug resistance in pancreatic cancer. PMID- 3105874 TI - Comparison of cell-associated and soluble galactosyltransferase isoenzymes from a human bladder transitional cell carcinoma line. AB - We investigated the asialo-agalactofetuin galactosyltransferase solubilized by Triton X-100 from a human bladder transitional cell carcinoma line (cell associated form). The specific activity of this enzyme was dependent on cell population density, being about 50% higher in cells from confluent than from sparse cultures. We compared the properties of this enzyme with those of a galactosyltransferase isoenzyme present in the culture medium (soluble form). Electrophoresis on nondenaturing polyacrylamide gels showed the two forms to be isoenzymes, in that the mobility of the soluble enzyme was greater than that of the cell-associated enzyme. The isoenzymes differed in that the Km for UDP galactose of the cell-associated enzyme (1 X 10(-5) M) was one-half that of the soluble isoenzyme. The isoenzymes differed by 1 order of magnitude in their affinity for a fetuin-derived acceptor with a Km of 16 X 10(-5) M for the cell associated and 1.2 X 10(-5) M for the soluble form, although the Km for ovalbumin and asialomucin as acceptor was similar for both. Both enzymes were active over a broad pH range and their response to divalent cations was the same: the most efficient cation was Mn2+; but modest activity was detected in the presence of either Cd2+ or Co2+. As determined by gel filtration on Sepharose 6B, the cell associated galactosyltransferase showed a molecular weight of 66,000, whereas that of the soluble form was 51,000. Limited proteolysis of the cell-associated enzyme with thermolysin and subsequent analysis by nondenaturing polyacrylamide gel electrophoresis demonstrated that the cell-associated enzyme could be converted to an isoenzyme showing the same electrophoretic mobility as the soluble enzyme present in the culture medium, presumably by removal of a portion of the peptide chain. The same result was obtained by treating the cell associated enzyme with a cell extract. This suggests but does not prove that the soluble enzyme secreted or shed into the medium is produced from the cell associated form by an endogenous protease. PMID- 3105875 TI - Ovarian toxicity of cyclophosphamide alone and in combination with ovarian irradiation in the rat. AB - The effects of radiation and chemotherapy on gonadal function are relevant to the morbidity induced by such treatments. Cyclophosphamide given i.p. to rats on Day 30 of age delayed vaginal opening, prevented vaginal cyclicity, and caused a reduction in serum estradiol and progesterone. Antral follicular atresia increased in a dose-dependent fashion in response to cyclophosphamide (0 mg/kg, 53.5%; 1 mg/kg, 67.3%; 50 mg/kg, 65.7%; 100 mg/kg, 73.9%; 150 mg/kg, 92.2%). Despite such alterations in ovarian function, serum gonadotrophins did not rise. The concurrent administration of 0, 20, 30, 40, 50, and 60 Gy of radiation to the exteriorized ovaries in rats receiving 50 mg/kg cyclophosphamide induced widespread loss of primordial, preantral, and healthy antral follicles associated with reduction in serum progesterone and estradiol. Such irradiation induced dose related increases in serum follicle-stimulating hormone and luteinizing hormone. Parenteral cyclophosphamide and local irradiation appear to induce ovarian toxicity by different mechanisms. PMID- 3105876 TI - Nutritional requirements of human malignant (leukemic) cell lines: implications for adjuvant therapy. AB - Metabolic requirements of malignant cell lines derived from patients with chronic myelogenous and acute lymphoblastic leukemias were compared to those of proliferating normal cells (mitogen-stimulated human lymphocytes) and circulating blasts from acute myeloblastic and acute lymphoblastic leukemias. Requirements were judged by degree of amino acid (AA) utilization in short-term cultures and assessed by the effect of selective AA deprivation on cell growth. Cell growth was measured by DNA synthesis and growth rate analysis. Six AAs (serine, threonine, methionine, valine, phenylalanine, and lysine) were appreciably utilized (52-87%) by IM-9, CEM, MOLT-4, and K-562 cells, but little or no utilization of these or any other AAs were noted in HSB cells, in leukemic blasts, or in mitogen-stimulated normal lymphocytes in short-term culture. Omission of lysine from culture media greatly inhibited cell growth (DNA synthesis by 91%), and cell density (by 83%) of IM-9 cells. However, omission of lysine, valine, serine, threonine, methionine, or phenylalanine had less of an effect on CEM and MOLT-4 cell lines. These observations demonstrate that under the conditions used the IM-9 cell line is uniquely dependent on extracellular lysine levels in contrast to the other cell lines studied. This suggests that human malignancies other than acute lymphoblastic leukemia which exhibits an obligate dependence on extracellular asparagine might be manageable by enzymatic degradation in vivo or by dietary restriction of indispensable AAs. PMID- 3105877 TI - Relative importance of incision and polymerase activities in determining the distribution of damaged sites that are mended in xeroderma pigmentosum group C cells. AB - Those pyrimidine dimers that are repaired in confluent xeroderma pigmentosum Group C cells are clustered together in the genome. Although the average level of repair in this complementation group is of the order of 25% of normal, this percentage represents normal levels of repair in one quarter of the genome and little repair in the remainder. The factors that regulate this clustering process have been investigated using inhibitors of the initial incision step of repair (novobiocin) and of the polymerization step (aphidicolin). Novobiocin at a concentration that permitted 30% of repair to continue reduced the clustering of mended sites only slightly. Aphidicolin, in contrast, at a concentration that permitted 30 to 60% of repair to continue caused the mended sites to be distributed randomly. The clustering of repair sites seen in xeroderma pigmentosum Group C cells, therefore, is produced by an excision repair mechanism in which an aphidicolin-sensitive DNA polymerase, presumably alpha, plays an important regulatory role in determining which damaged sites are mended. PMID- 3105878 TI - 5-HT reuptake inhibitors in healthy human subjects. PMID- 3105879 TI - New neuroendocrine aspects of depression and anxiety. PMID- 3105880 TI - Guanine nucleotide regulatory proteins and signal transduction in the CNS- multiple mechanisms. PMID- 3105881 TI - Phase I-II study of eflornithine and mitoguazone combined in the treatment of recurrent primary brain tumors. AB - Eflornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and mitoguazone (MGBG), a competitive inhibitor of S-adenosylmethionine decarboxylase, were evaluated in a phase I-II study for patients with primary recurrent malignant brain tumors. All patients had failed prior radiation therapy and most had also failed prior chemotherapy. Two dose schedules were used, with the second schedule (Group II) a modification of the first schedule (Group I). The Group II schedule, with different dose levels, was better tolerated than the Group I schedule. Gastrointestinal and myelotoxicity were dose-limiting in most patients, and tinnitus was dose-limiting in two patients. Nineteen of 33 evaluable patients had anaplastic gliomas, in whom response was observed in 21%, stable disease in 53%, and immediate progression after one course of therapy in 26%. Of six patients with glioblastoma multiforme, two had brief stabilization of disease. An additional patient with brainstem glioma and ependymoma also had disease stabilization. Four patients with medulloblastoma, a spinal cord mixed glioma, and one with oligodendroglioma failed DFMO-MGBG. Based on this study, we believe that a combination of DFMO and MGBG is well-tolerated and deserves further evaluation for patients with anaplastic gliomas, particularly those that appear to be biologically slow growing. PMID- 3105883 TI - 3,7-Anhydro-2-azi-1,2-dideoxy-D-glycero-L-manno-octitol, a photoaffinity label for beta-D-galactosidase from E. coli. PMID- 3105882 TI - Transfer of D-galactosyl groups to 6-O-substituted 2-acetamido-2-deoxy-D-glucose residues by use of bovine D-galactosyltransferase. AB - Bovine D-galactosyltransferase was found to transfer D-galactose from UDP galactose to 6-O-substituted 2-acetamido-2-deoxy-beta-D-glucopyranosides. The resulting 6-O-substituted N-acetyllactosamines were readily synthesized in milligram amounts and conveniently isolated on a reverse-phase support when prepared as the 8-methoxycarbonyloctyl glycosides. The 6-O-substitution tolerated by the enzyme include an alpha-L-fucopyranosyl group and the methyl ester of alpha-linked N-acetylneuraminic acid, but not the free acid itself. The product trisaccharides were characterized by 1H-n.m.r. spectroscopy and fast-atom bombardment mass spectrometry. PMID- 3105885 TI - Re: Works published in CVIR by Robert A. Slutsky, M.D. PMID- 3105884 TI - Neoglycolipid micro-immunoassays applied to the oligosaccharides of human milk galactosyltransferase detect blood-group related antigens on both O- and N-linked chains. AB - Reduced O-linked chains and reducing N-linked chains were obtained from human milk galactosyltransferase by degradation with alkaline borohydride and hydrazinolysis, and then purified by ion-exchange chromatography. The reactivities of the conjugates of the oligosaccharides with L-alpha-phosphatidyl ethanolamine dipalmitoyl (PPEADP) towards monoclonal anti-Lea and anti-SSEA-1 were then determined, either by antibody-binding assays after absorbing the neoglycolipids onto plastic wells, or by inhibition assays after incorporating the neoglycolipids into liposomes and testing them as inhibitors of antibody binding. The oligosaccharides were also immunostained with monoclonal anti-Lea after h.p.t.l.c. and coupling to PPEADP. Antigenic activities were detected in the O-linked chains by all three assay systems, whereas, for the less abundant N linked chains, reactivities were detected by the inhibition assays only. The results provide evidence for the expression of Lea and SSEA-1 antigen activities on both the O- and N-linked chains of this enzyme glycoprotein. PMID- 3105886 TI - Postoperative intravenous administration of lysine acetylsalicylate: effect on pain relief and platelet function. AB - The effects of lysine acetylsalicylate, a new injectable salicylate, on postoperative pain relief and platelet function were studied in ten men who had surgery for peptic ulcer. Four of five patients receiving lysine acetylsalicylate had satisfactory pain relief. One patient required an additional injection of 15 mg of pentazocine. Of the five patients in the control group, an average (+/- SD) dose of 90 +/- 23.7 mg of pentazocine was required to achieve adequate postoperative pain relief. Lysine acetylsalicylate decreased platelet aggregability but without resulting in hemorrhage. We concluded that this new salicylate administered intravenously to patients in the postoperative period provided adequate analgesia while allowing effective hemostasis despite its inhibitory effect on platelet aggregation. PMID- 3105887 TI - Interaction of saccharin with hexitol metabolism by Streptococcus mutans. PMID- 3105888 TI - Purification and characterization of an acidic beta-galactosidase from rabbit kidney. PMID- 3105889 TI - Structural changes at pure cholinergic synaptosomes during the transmitter release induced by A-23187 in Torpedo marmorata. A freeze-fracture study. AB - Pure cholinergic synaptosomes isolated from the electric organ of Torpedo marmorata were stimulated by calcium ionophore A-23187. The effect of time course of stimulation on the changes in intramembrane particles (IMPs) on presynaptic membranes was studied by quick-freezing and aldehyde-fixation freeze-fracture. We showed that the decrease of small-particle density at the P-face and the increase of large-particle density at the E-face was maximum after 30 sec of A-23187 stimulation. Later, the density of synaptic vesicles decreased. We suggest that the redistribution of IMPs on the presynaptic membrane and acetylcholine (ACh) release from pure cholinergic synaptosomes have a similar time course when triggered by A-23187. PMID- 3105891 TI - Single dose metrifonate in the treatment of urinary schistosomiasis in an area of low prevalence and intensity of infection. PMID- 3105890 TI - Ultrastructural demonstration of nerve endings containing a substance related to growth hormone-releasing factor in the guinea-pig paraventricular nucleus. AB - By means of a preembedding immuno-electron-microscopic technique, a large number of nerve endings containing a substance related to human growth hormone-releasing factor (hGRF) have been demonstrated in the paraventricular nucleus of the guinea pig. They made synaptic contacts primarily with dendritic shafts: 80% of these contacts were symmetrical. The immunoprecipitate was located mainly in large granules and around small clear vesicles. These findings suggest that a peptide related to hGRF may play a role in neural communication in the paraventricular nucleus. PMID- 3105892 TI - Autonomous requirements for the segment polarity gene armadillo during Drosophila embryogenesis. AB - Embryos hemizygous for armadillo produce a "segment polarity" phenotype in which the naked posterior two-thirds of each segment is replaced by denticles with reversed polarity. Small patches of homozygous arm cells induced by mitotic recombination also form such denticles, indicating that the changes in cellular fate observed in homozygous arm embryos are autonomous at the level of single cells. Clonally derived arm patches do not, however, show the characteristic arm polarity reversals, arguing that this feature of the phenotype depends on cell interactions in fully mutant embryos. Few, if any, clones were found in the posterior-most regions of the naked cuticle, and none were found in the posterior compartments of the thorax. PMID- 3105893 TI - Three types of muscle-specific gene expression in fusion-blocked rat skeletal muscle cells: translational control in EGTA-treated cells. AB - When rat skeletal muscle cells were treated with EGTA, an inhibitor of cell fusion, a battery of muscle-specific mRNAs was synthesized but not translated despite the synthesis of many other proteins. Most of the muscle-specific mRNAs were associated with polysomes in fused myotubes, whereas they were found in postpolysomal fractions in EGTA-treated cells. Therefore, in addition to the well documented transcriptional and posttranscriptional control of muscle-specific genes, translational control of this specific group of genes, presumably involving a Ca2+-dependent process, is also observed in these fusion-blocked cells. These findings and results obtained with other fusion inhibitors demonstrate that three types of muscle-specific gene expression take place in the fusion-blocked cells depending on the inhibitors used: one, neither muscle specific mRNAs nor proteins are synthesized; two, the mRNAs are synthesized but not translated; and three, both the mRNAs and the proteins are synthesized. PMID- 3105895 TI - Triggering of interferon gamma-primed macrophages by various known complement activators for nonspecific tumor cytotoxicity. AB - Five known complement activators were evaluated for their capacity to directly activate murine macrophages and to trigger activation of lymphokine primed macrophages for nonspecific tumor cytotoxicity. Bacterial lipopolysaccharide (LPS), Lipid A, polyinosinic-polycytidylic acid, cobra venom factor (CVF), and zymosan directly activated macrophages in a dose-dependent fashion at high concentrations. Subactivating concentrations of each of these agents were found to effectively trigger macrophages which were preprimed either by macrophage activating factor or by murine recombinant interferon gamma for enhanced tumoricidal activity. An Fc receptor blockade with opsonized sheep erythrocytes abrogated LPS-mediated direct activation and triggering of interferon gamma primed macrophages, but had no inhibitory effect on direct activation or triggering by CVF for nonspecific tumor cytotoxicity. This study characterizes the capacity of a diverse group of known complement activators to serve as second signal triggers for culmination of the activation process of interferon-primed macrophages for nonspecific tumoricidal activity. These findings suggest that complement activators may directly activate macrophages by stimulation of interferon beta production by macrophages for self-priming and, as we have shown, act as self-triggers. The putative role of macrophage-associated complement components in the activation process is discussed. PMID- 3105894 TI - Interleukin 2 responsiveness of immature T-cell colony-forming cells (T-CFC) from patients with acute T-cell lymphoblastic leukemias. AB - T-cell colony-forming cells (T-CFC) from 13 of 17 patients with T-ALL generated colonies in methylcellulose in the absence of added growth factors or mitogenic stimulation. As previously described, these colonies were composed of immature T cells displaying the same karyotypic abnormalities as fresh leukemic cells. Biochemically purified (bIL-2) and recombinant IL-2 (rIL-2) without any mitogen enhanced colony growth from both unfractionated and blast-enriched cell fractions in patients with a relatively low (less than 50 colonies/5 X 10(4) cells) plating efficiency. However, dose-response experiments revealed that the optimal dose of rIL-2 needed to enhance colony growth varied from patient to patient. Anti-IL-2 (DMS1) and anti-IL-2 receptor (anti-Tac) moAbs inhibited both spontaneous and rIL 2-induced colony formation in a dose-dependent manner. Direct staining of fresh leukemic cells with anti-Tac revealed less than 10% positive cells in all but two patients. However, cell incubation in the absence of growth factors or mitogens for 2-48 hr resulted in an increase of Tac+ cells. These observations indicate that a subset of immature T-CFC from T-ALL patients display functional IL-2 receptors. In addition, our findings strongly suggest that the IL-2/IL-2-R system could be involved in the spontaneous proliferation of some immature T-CFC of T ALL patients. PMID- 3105896 TI - A significant role of the macrophage accumulation induced by MCF in the protection of mice against Listeria monocytogenes in vivo. AB - Analysis was done on macrophage chemotactic factor (MCF) produced in the culture supernatant of spleen cells from mice immunized with Listeria monocytogenes. MCF was produced by Thy-1+, Lyt-1+ lymphocytes. MCF activity was resistant against pH 2 treatment and heating at 56 degrees C for 30 min, but was abolished by digestion with trypsin. G-100 gel filtration chromatography revealed that the approximate molecular weight of MCF was 15,000. MCF-rich fraction obtained by gel filtration chromatography showed neither MAF activity nor interferon activity. MCF activity in MCF-rich fraction was not affected by treatment with anti-rIFN gamma antibody. An injection of MCF-rich fraction into the peritoneal cavity of mice induced a significant degree of accumulation of polymorphonuclear leukocytes (PMN) in a very short time after injection and macrophages thereafter. Resistance against listerial infection was augmented at the site where macrophage accumulation was provoked by the injection with MCF-rich fraction. It was shown that MCF plays an important role by itself in the protection against listerial infection by the accelerated accumulation of macrophages. PMID- 3105897 TI - Enhancement of human T-lymphocyte growth by human transferrin in the presence of fetal bovine serum. AB - All dividing cells require transferrin as a growth factor. During in vitro culture of human lymphocytes, transferrin is usually supplied in the form of serum, either synergic or xenogenic (usually fetal bovine serum (FBS)). In the present work the growth of certain human T-cell lines was examined; these lines were derived from the synovium of rheumatoid arthritis patients and maintained in 10% FBS and 1% synovial fluid. Their growth especially at limiting dilutions was found to be strongly dependent on the presence of synovial fluid at low concentration (0.05-0.1%) in culture medium containing 10% FBS. Further studies indicated that this effect of synovial fluid was duplicated by human serum or plasma, and was due to the presence of human transferrin. A significant effect on T-cell growth was observed using 2 micrograms/ml human transferrin with optimal growth at 10-20 micrograms/ml. This requirement for human transferrin was not a peculiarity of the synovium-derived T-cell lines, but was observed with all T cell lines tested irrespective of phenotype or function. These observations suggest that bovine transferrin is inadequate for T-cell growth, and that the growth enhancing properties of FBS do not primarily reflect the provision of transferrin. Since some T cells have recently been shown to be capable of secreting transferrin upon activation, endogenous synthesis of transferrin may be an important factor in the in vitro growth of T cells so that such cells would be selected when FBS is the source of serum used to grow human T-cell lines or clones. PMID- 3105898 TI - Intracellular polyamine biosynthesis is required for interleukin 2 responsiveness during lymphocyte mitogenesis. AB - The objective of the present investigation was to define a more precise role for intracellular polyamine biosynthesis with respect to specific inducible events which regulate lymphocyte mitogenesis. In this regard, we have examined the effect of polyamine depletion on interleukin 2 (IL-2) production, receptor expression, and responsiveness in Con A stimulated mononuclear leukocytes (MNL). Polyamine depletion was achieved utilizing the specific irreversible inhibitor of ornithine decarboxylase (ODC), DL-alpha-difluoromethylornithine (DFMO). Polyamine depletion of MNL augmented detectable levels of Con A-induced IL-2 activity. In contrast, the ability of polyamine depleted MNL to respond to saturating levels of IL-2 (100 U/ml) following 72 or 96 hr of Con A stimulation was reduced 100 and 81%, respectively. Nonetheless, polyamine depletion did not impair the induction of IL-2 receptor expression. High-affinity IL-2 receptor density in the polyamine depleted population was greater than control cells late in culture (96 hr). The expression of high-affinity IL-2 receptors did not correlate with an ability to respond to IL-2 in the polyamine depleted population. The results of this study demonstrate for the first time that intracellular polyamine biosynthesis is required for IL-2 responsiveness during a primary mitogenic lymphocyte response. PMID- 3105899 TI - The effects of cytokines and adherent cells on the interleukin 4-mediated induction of Ia antigens on resting B cells. AB - In this report we have extended our previous studies on interleukin 4 (IL-4) [previously termed B-cell stimulatory factor-1 (BSF-1)]. Our results demonstrate that 8 hr of exposure to IL-4 is sufficient to induce maximal expression of Ia antigens. This increase in expression of Ia antigens on resting B cells is due to the direct action of IL-4 on the B cells since adding or removing adherent cells or utilizing low density cultures of B cells at 50-100/culture had no effect on the IL-4-mediated increase in Ia. Monoclonal anti-IL-4 antibody completely abrogated the Ia-inducing activity of IL-4. A variety of other purified lymphokines including interleukin 2 (IL-2), interleukin 1 (IL-1), and a source of either B-cell differentiation factor for IgM (BCDF mu), or B-cell growth factor II (BCGF II), did not alter the expression of Ia antigens on resting B cells. However, interferon-gamma can partially inhibit the IL-4-mediated induction of Ia. PMID- 3105900 TI - [The effect of amniotic fluid on the growth of Neisseria gonorrhoeae]. PMID- 3105901 TI - Genetic study on ossification of posterior longitudinal ligament. AB - Family studies and blood grouping tests were conducted in an attempt to elucidate the etiology and genetic mechanism of ossification of posterior longitudinal ligament of the spine (OPLL). Analysis of the collected date revealed the following results: Testing of inheritance pattern Fitness of OPLL to the hypotheses of simple recessive inheritance, simple dominant inheritance and multifactorial inheritance was tested, but fitness to any one of these hypotheses was statistically denied. Analyses of OPLL and genetic markers A comparative study was made between the OPLL patients and healthy donors residing in Tokyo on the phenotype frequency of the blood groups (eight systems), serum groups (six systems) and red cell enzyme groups (three systems). A significant association of OPLL with MN blood groups, Hp types and PGM1 types was observed. Examination of the correlation after combining MN and Hp showed the coefficient of contingency to be C = 0.6739 and that after the multiple combination of MN, Hp and PGM1 revealed the coefficient of contingency to be C = 0.8923, indicating a remarkably high correlation. PMID- 3105902 TI - Slicing technique for tooth specimens in histological preparation. AB - A slicing technique for the preparation of a tooth specimen is described. A low speed saw (ISOMET) was used for this modified technique. It is a slicing machine fitted with a diamond-impregnated cutting disc of 0.5 mm in thickness. The formalin was used for lubrication to serve as both a coolant and a fixative simultaneously. It is thought that the preparation will not damage or disturb the surface of the tooth specimen by careful management under 200 rpm with a loading of 50 grams. The cutting of slices can be controlled by adjusting the specimen arm with a micrometer to the desired thickness. A high quality histological preparation can be obtained when the specimen is sliced as mentioned above soon after it is removed from the living body before decalcification. By the observation of specimens such as the resected jaw bone or other large hard tissue specimens, it is suggested that the sliced specimens of 2 mm in thickness can be obtained routinely for histological study by using this method. PMID- 3105903 TI - Thymidylate synthetase and thymidine kinase activities in DMH-induced colon carcinomas in rats and effects of UFT. AB - Carcinoma of the colon was induced in rats by injection of a carcinogen 1,2 dimethylhydrazine (DMH), and thymidylate synthetase (TS) and thymidine kinase (TK) activities, which catalyze the biosynthesis of dTMP by the de novo pathway and the salvage pathway of pyrimidine synthesis, respectively, were measured in normal control colon, DMH-treated normal colon, and DMH-induced colon carcinoma with or without administration of two doses of an anti-cancer drug UFT (a combination of tegafur and uracil). TS and TK activities were both increased after treatment with DMH, markedly in colon carcinoma tissue, and to a lesser degree in normal-appearing colon tissue. This phenomenon is well explained by the hypothesis that biochemical alterations of DNA-synthesizing enzyme activities occur as a preliminary step prior to the development of overt cancerous transformation. A low dose of UFT inhibited TS activity but enhanced TK activity, therefore, the salvage pathway may compensate for the reduced level of the de novo synthesis. On the other hand, a large dose of UFT reduced both TS and TK activities, perhaps due to cytotoxic effects of UFT incorporation into RNA. PMID- 3105904 TI - Studies on the mechanism of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) induced hepatotoxicity. II. Biochemical and morphological characterization of the injury and its prevention by phenobarbital. AB - The present study characterizes the biochemical, morphological, and histological sites of CCNU-induced hepatotoxicity and investigates the effect of modifiers of drug metabolism on this toxicity. A single oral dose (100 mg/kg) of CCNU caused four- and ninefold increases in serum GOT and GPT respectively 48 h after administration in rats. A 25-fold rise in serum bilirubin, a total loss of bile flow, and a decrease in BSP clearance were also observed. Cytochrome P-450 content and EM-N-demethylase activity were significantly decreased to 88% and 66% of control values respectively. A histopathological time course study of CCNU induced injury showed a progression of acute inflammation, edema, and fibrin deposition in portal areas over 24 h with necrosis and sloughing of bile duct epithelium at 24 and 36 h. Treatment of rats with PB (40 mg/kg/day for 4 days, i.p.) 24 h prior to CCNU administration protected against CCNU-induced hepatotoxicity. Thus, the levels of serum GOT, GPT, and bilirubin were only 2.5 and 4 times higher than in untreated or PB-treated controls. Histopathological examination also showed reduced severity of bile duct lesions in PB-pretreated animals. In rats receiving both PB and CCNU, bile flow was restored and BSP clearance was increased compared to the CCNU-treated rats. The mixed-function oxidase activity in PB + CCNU-treated rats was not significantly different from that in PB-treated controls. It is concluded that pretreatment of rats with PB can markedly suppress the hepatotoxic manifestations, including histopathological changes, the rise in serum bilirubin, and the cholestasis observed in CCNU treated rats. PMID- 3105905 TI - Single and repeated dose pharmacokinetics of thio-TEPA in patients treated for ovarian carcinoma. AB - Triethylenethiophosphoramide (thio-TEPA) pharmacokinetics were studied in 15 patients being treated for epithelial ovarian carcinoma. Unchanged thio-TEPA was assayed in serum and urine by means of a gas chromatographic procedure. No accumulation or alteration of the pharmacokinetics occurred during therapy, which was continued for up to 7 months with biweekly administrations of 20 mg, after two initial loading courses with 20 mg daily for 3 consecutive days 2 weeks apart. No significant difference in the pharmacokinetics between i.m. and i.v. administration was demonstrated. However, three patients showed a reduced absorption ability from the i.m. injection site to the systemic circulation and an apparent increase in the elimination half-life (3.86 +/- 0.97 h), which could be of clinical relevance. A first-order elimination process with a short elimination half-life (approximately 1.5 h) was demonstrated for thio-TEPA in all patients after i.v. administration. The apparent volume of distribution averaged 50 1. The renal clearance was below 1% of the total-body clearance, which averaged 412 ml/min. The urinary excretion of unchanged thio-TEPA was complete within 8 h after administration, with an average urinary recovery of 0.14% of the dose. Calculation of the area under the serum concentration vs time curve revealed wide variation between patients (range 517-1480 ng/h ml-1), indicating the need for drug monitoring during therapy. PMID- 3105906 TI - Failure to preserve fertility in patients with Hodgkin's disease. AB - The hypothesis that the "down-regulated" gonad is less vulnerable to the effects of cytotoxic chemotherapy for advanced Hodgkin's disease has been investigated. Thirty men and eighteen women were randomly allocated to receive an agonist analogue of gonadotrophin-releasing hormone prior to, and for the duration of, cytotoxic chemotherapy. Buserelin (d-Ser-[TBU]6 LHRH ethylamide) was prescribed in two different dosage schedules to twenty men, and in a single dosage schedule to eight women. A standard gonadotrophin-releasing hormone test (GnRH 100 micrograms) was performed 1 week prior to and on day 1 of each cycle of chemotherapy. In all patients peak luteinizing hormone responses to GnRH were suppressed throughout treatment. The higher of the two dosage schedules used in the men caused more effective suppression of luteinizing hormone, and both regimens led to an initial suppression of peak follicle-stimulating hormone responses to GnRH, which was not maintained. At follow-up assessment up to 3 years from the completion of treatment, all men treated with buserelin were profoundly oligospermic and four of the eight women were amenorrhoeic. All ten male controls were profoundly oligospermic, and six of nine female controls were amenorrhoeic. In the dosages and schedules investigated, buserelin was ineffective in conserving fertility. PMID- 3105907 TI - Transient pulmonary platelet sequestration during endotoxemia in dogs. AB - We evaluated the time-course of regional platelet sequestration, following a bolus dose of endotoxin in anesthetized dogs. Autologous indium 111 labeled platelets, representing less than 1% of the circulating platelets, were injected 35-60 min prior to administering endotoxin intravenously to dogs. A gamma camera was used to monitor the distribution of these platelets within the thorax and abdomen. Alterations in the circulating blood platelet count paralleled the changes in blood radioactivity, enabling us to use external imaging to evaluate platelet kinetics. Marked hypotension and thrombocytopenia occurred within 6 min after administering endotoxin. The platelet pool in the lungs peaked at 9 min and was temporally related to the decrease in circulating platelet count, hypotension and increase in liver size. Translocation of platelets from the lungs to the circulating platelet pool occurred during the subsequent hour with sequestration occurring in the liver and possibly other organs. During this phase there was a recovery in platelet count to 35% of baseline levels but without significant recovery in mean arterial pressure. Based on these results we propose that endotoxin-induced thrombocytopenia results from pulmonary and hepatic sequestration of platelets, but that sequestration of platelets in the lungs is only transient. The mechanism and significance of subsequent translocation of platelets from the lungs to other sites, particularly the liver and the circulating platelet pool, remain to be investigated. PMID- 3105908 TI - Cardiorespiratory alterations produced by centrally administered thyrotropin releasing hormone during canine endotoxin shock. AB - Endogenous opiates have been implicated in the pathophysiology of endotoxin, hemorrhagic, and spinal shock. Blockade of these compounds with peripherally or centrally administered naloxone has been shown to produce beneficial effects. More recently, it has been suggested that thyrotropin-releasing hormone (TRH) may be able to block the detrimental effects of endogenous opiate compounds without removing their analgesic effects. Improved cardiovascular function during endotoxin shock has been demonstrated in rat and primate models; however, this drug has not been tested in the canine endotoxin shock model. The present study was designed to determine if TRH administered through ventriculocisternal (VC) perfusion could significantly improve cardiorespiratory function during canine endotoxin shock. Cardiac output, arterial pressure, end-tidal CO2, heart rate, respiratory rate, pulse pressure, and total peripheral resistance were determined for three separate groups of animals. One group of animals received TRH only and served as a drug control. One of the remaining groups received endotoxin only, while the other group received endotoxin plus TRH. The results of the study suggest that TRH administered centrally is capable of improving cardiac output during endotoxin shock. No significant difference was found in any of the other parameters measured. Based on these findings, it can be concluded that TRH has a minimal effect during canine endotoxin shock. The discrepancy between these results and those from other endotoxin shock models may result from species variation, TRH metabolism and sensitivity, and/or anesthetic effect. PMID- 3105909 TI - Intestinal vasodilation by epoxyeicosatrienoic acids: arachidonic acid metabolites produced by a cytochrome P450 monooxygenase. AB - Purified synthetic products from the cytochrome P450 pathway of arachidonate metabolism were applied to the intestinal serosa. Arteriolar blood flow was calculated using video microscopy. After a steady-state baseline, a bolus containing 10-60 micrograms 14,15-epoxyeicosatrienoic acid/ml (14,15-EET) had no detectable effect on blood flow. However, 25 +/- 3 micrograms 11,12-EET/ml and 36 +/- 2 micrograms 8,9-EET/ml caused increases (134 +/- 8% and 127 +/- 6%) that were similar to those elicited by 8 +/- 2 micrograms adenosine/ml (138 +/- 12%). Furthermore, the increases (275 +/- 38%) produced by 32 +/- 6 micrograms 5,6 EET/ml exceeded those elicited (160 +/- 10%) by a similar concentration (27 +/- 3 micrograms/ml) of adenosine. Thus, a structure-activity relationship is suggested. Nevertheless, these values probably underestimate the potency of the EETs because the vasoactivity was reduced by contact with water. The activity of the cyclooxygenase pathway seemed to limit the formation of vasoactive quantities of EETs, or other nonprostanoids, from exogenous arachidonate in the serosa but not the mucosa. A bolus (1.3 +/- 0.2 mg/ml) or continuous application (122 +/- 45 micrograms/ml) of arachidonate caused blood flow increases (236 +/- 14% or 229 +/ 27%) that were almost eliminated (129 +/- 5% or 121 +/- 9%) by a cyclooxygenase inhibitor; the residual response was abolished by a cytochrome P450 inhibitor. However, cytochrome P450 inhibitors alone did not attenuate the arachidonate response. In contrast, a continuous application of 194 micrograms arachidonate/ml to the mucosa caused a markedly smaller blood flow increase (119 +/- 8%) and cyclooxygenase inhibitors potentiated (132 +/- 8%), rather than reduced, this response. We conclude that EETs are a labile class of vasodilators with a potency comparable to adenosine in the intestinal microcirculation. Indirect evidence suggests regional differences in the formation of vasoactive quantities of arachidonate metabolites within the intestinal wall. PMID- 3105911 TI - [Use of dot-ELISA in the diagnosis of schistosomiasis]. PMID- 3105910 TI - [A comparative study of COP and IHA in the epidemiological evaluation of schistosomiasis japonica in eradicated endemic area]. PMID- 3105912 TI - [Effects of praziquantel and artemether on tegumental surface antigens of different developmental stages of Schistosoma japonicum]. PMID- 3105913 TI - A randomized, blinded, placebo-controlled trial of recombinant human tissue-type plasminogen activator in patients with unstable angina pectoris. AB - Twenty-four patients with unstable angina pectoris, defined as chest pain at rest with transient ST segment deviation of at least 1 mm, were randomly assigned to blinded treatment with either placebo or intravenous recombinant human tissue type plasminogen activator (rt-PA). Before randomization, all patients were treated with oral beta-blockers, calcium antagonists, nitrates, and continuous intravenous heparin for a monitoring period of 12 to 28 hr. After this monitoring period the 24 patients were randomly assigned to receive either placebo or 1.75 mg/kg intravenous rt-PA given over 12 hr at a rate of 0.75 mg/kg over 1 hr, 0.5 mg/kg over 4 hr, and 0.5 mg/kg over 7 hr. One patient, assigned to receive placebo, developed acute myocardial infarction after randomization but before receiving the study drug. Ischemic events were recorded during a hospital follow up period of at least 4 days unless a further intervention was indicated or the coronary angiogram was normal. The follow-up period was 7 +/- 5 days (mean +/- SD) after the placebo infusion and 8 +/- 4 days after the infusion of rt-PA. Unstable angina pectoris persisted after the completion of the infusion in six of 11 patients receiving placebo and only one of 12 patients receiving rt-PA (p less than .03). Coronary angiography, performed 38 +/- 19 hr after the infusion, demonstrated subocclusive thrombus in eight of 11 patients receiving placebo but in none of 11 patients treated with rt-PA (p less than .002). One patient on rt PA refused coronary angiography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3105914 TI - Recombinant tissue plasminogen activator in patients with pulmonary embolism: correlation of fibrinolytic specificity and efficacy. AB - Blood samples from 24 patients who received recombinant human tissue-type plasminogen activator (rt-PA) for angiographically documented acute pulmonary embolism were examined to identify and quantify fibrinolysis. Before and after the intravenous administration of 50 mg rt-PA over a 2 hr period, levels of total fibrinogen, fibrin(ogen) degradation products (FDP), and cross-linked fibrin degradation products (XDP) were measured in each patient. Elevated levels of XDP were found in all patients before treatment (mean 2.0 micrograms/ml, normal less than 0.2 microgram/ml), and these increased 12-fold with treatment. Fibrinogen levels fell 30% and FDP levels increased 24-fold for the entire group of patients. Over this 2 hr period, 10 of 24 patients (responders) demonstrated 25% or greater improvement in the extent of pulmonary artery thrombus as quantified by Urokinase Pulmonary Embolism Trial score, and these patients were found to have a significantly lower XDP/FDP ratio after rt-PA (p less than .04) than those patients who failed to respond. These data suggest that the intravenous administration of pharmacologic doses of rt-PA in patients with pulmonary embolism produces both fibrinolysis and fibrinogenolysis, successful thrombolysis in these patients is associated with a preponderance of fibrinogenolysis over fibrinolysis, the XDP/FDP ratio is a useful indicator of fibrinolytic specificity, and in patients with acute pulmonary embolism the endogenous fibrinolytic pathways are activated, albeit ineffectively, as indicated by the increased circulating XDP levels seen in all 24 patients before the administration of rt-PA. PMID- 3105916 TI - [The anti-shock effect of the acupoint renzhong and characteristics of its hemodynamics]. PMID- 3105917 TI - [The pressor reaction induced by acupuncture and its physiological characteristics]. PMID- 3105915 TI - Intramuscular administration of human tissue-type plasminogen activator in rabbits and dogs and its implications for coronary thrombolysis. AB - To determine whether sustained plasma concentration of human tissue-type plasminogen activator (t-PA) can be induced promptly after intramuscular injection with enhancers of absorption devoid of deleterious local and systemic effects, we studied 250 rabbits and 13 dogs. In rabbits with t-PA injected directly into exposed muscle followed by local electrical stimulation at the site, early absorption was increased markedly by addition of 0.63M methylamine plus 0.079M hydroxylamine to the excipient. Elevations peaked within 5 min and increased with dose of t-PA, concentration of methylamine, and volume of injection medium. The enhancers were effective with percutaneous injections in the absence of local electrical stimulation as well. They did not elicit any obviously deleterious local or systemic effects. In separate experiments in rats, intramuscular injections of 0.63M methylamine plus 0.079M hydroxylamine induced local egress of intravascular radiolabeled albumin within the injection site and endothelial gaps in venules detected with colloidal carbon--changes consistent with direct effects on vascular permeability. In dogs, percutaneous intramuscular injection of t-PA in excipient without enhancers did not lead to early elevations of human t-PA in plasma, although late elevations were seen. When the enhancers were used, early elevations occurred as well, with functional activity documented by fibrin plate assays of serially obtained plasma samples and by sequential coronary angiography delineating thrombolysis after experimentally induced coronary thrombosis. The results indicate that intramuscular administration of t PA with selected enhancers of absorption is a feasible approach for rapid induction of fibrinolysis. PMID- 3105918 TI - [Sympathetic innervation of rabbit liver parenchyma and the effect of acupuncture during hemorrhagic shock]. PMID- 3105920 TI - [The effect of acupuncture at renzhong on hepatic glycogen of rabbits during hemorrhagic shock--a histochemical study]. PMID- 3105919 TI - [The effect of acupuncture at renzhong on hepatic phosphorylase of rabbits during hemorrhagic shock. Histochemical observation]. PMID- 3105921 TI - The study of the acupuncture effect on experimental allergic shock in mice. PMID- 3105922 TI - The regulatory function of acupuncture of the stomach. PMID- 3105924 TI - [The observation of the influence of the post-acupuncture effect on the post operative motility function of the gastrointestinal tract with the electrogastrogram and electrointestinogram on the body surface]. PMID- 3105923 TI - [Acupuncture can influence the motile function of the stomach and intestine]. PMID- 3105925 TI - [Effects of electro-acupuncture (EA) on T lymphocytes from the peripheral blood of normal man]. PMID- 3105926 TI - [Observation of the effects of electro-acupuncture (EA) on some components of the complement system in normal man]. PMID- 3105927 TI - [Morphological observation on the effect of acupuncture on mast cells at the zusanli point]. PMID- 3105928 TI - Effect of acupuncture on prolactin secretion of lactating rats. PMID- 3105929 TI - [Clinical observation of the effect of acupuncture at the zusanli acupoint on hyperlipemia]. PMID- 3105930 TI - [The adjustable functional effect of acupuncture and moxibustion on the respective mechanisms of immuno-competence]. PMID- 3105931 TI - [The adjustable functional effect of acupuncture and moxibustion on the changing rate of various proteins, activity of blood cholinesterase fluctuational situation, and inorganic salt content]. PMID- 3105932 TI - Isolation and purification of creatine kinase conversion factor from human serum and its identification as carboxypeptidase N. AB - Creatine kinase conversion factor has been isolated from human serum and purified to electrophoretic and chromatographic homogeneity. The enzyme sequentially converts creatine kinase MM3 to MM2 and MM1 and hydrolyzes lysine and arginine from hippuryl-L-lysine and hippuryl-L-arginine. Data on molecular weight, (316,000 dalton), electrophoretic mobility (alpha-globulin), prevalence in serum (26 mg/L), subunit composition (two subunits, 80,000 and 52,200 dalton) indicate that creatine kinase conversion factor is identical to carboxypeptidase N. The previously reported lower molecular weight of 190,000 dalton of partially purified creatine kinase conversion factor is attributed to proteolytic degradation. PMID- 3105933 TI - Enhanced-latex-agglutination assay for C-reactive protein in serum, with use of a centrifugal analyzer. AB - This is an improved assay of C-reactive protein in serum, for use with the Baker "Encore" centrifugal analyzer. Features of this assay include: 250-specimen throughput per hour, within-batch CV 2.2%, between-batch CV 2.7%, no antigen excess problems up to 1000 mg/L, negligible interference from rheumatoid factor, and good correlation (r = 0.99) with radial immunodiffusion. The method is inexpensive and automated, involving no predilution steps. It can be adapted for use in a wide range of systems and can be used for single urgent estimations. PMID- 3105934 TI - Problems with blood gas analysis revisited. PMID- 3105936 TI - Anti-inflammatory activity of IFN-beta in carrageenan-induced pleurisy in the mouse. AB - The effect of IFN-beta on the development of the inflammatory reaction was studied in an experimental animal model, carrageenan-induced pleurisy in the mouse. Intrapleural inoculation of IFN-beta at the same time as carrageenan administration inhibited both migration of inflammatory cells and exudate formation in the pleural cavity in a dose-dependent fashion. Similarly, IFN-beta decreased the presence of the arachidonate metabolites PGI2, TXA2 and PGE2 (highly active molecules involved in the regulation of the inflammatory reaction) in inflammatory exudates. A marked inhibition of the inflammatory response to carrageenan was also evident when IFN-beta was administered several hours after the inflammatory challenge. In contrast, administration of IFN-gamma did not modify significantly any of the inflammatory parameters considered. PMID- 3105935 TI - Inhibition of lymphocyte motility by interleukin 2. AB - These studies described were designed to determine whether interleukin 2 (IL-2) inhibits lymphocyte migration. The human lymphoblastoid cell line QIMR-WIL was used as an indicator of lymphocyte migration inhibition. Interleukin 2 inhibited QIMR-WIL migration in a dose-dependent manner, high doses of IL-2 (100 units) being strongly inhibitory, and low doses (12.5 units) less inhibitory. Purified natural IL-2 and recombinant IL-2 both inhibited QIMR-WIL migration. The effect of IL-2 on lymphocyte migration was specific. When the IL-2 receptors were blocked with anti-Tac (anti-IL-2 receptor) antibodies, the inhibitory effect of IL-2 was significantly reduced. Similarly antibody to IL-2 blocked the inhibitory effect of IL-2. Lymph node lymphocytes were also used as indicator cells in migration studies and IL-2 inhibited their motility. These data suggest a role for IL-2 in inhibiting lymphocyte migration similar to that of lymphocyte migration inhibition factor produced by antigen- or mitogen-stimulated T lymphocytes. While it is widely recognized that lymphocyte motility can be reduced by lymphocyte migration inhibition factor, these data indicate that IL-2 can also reduce lymphocyte motility. PMID- 3105937 TI - Is the serum amyloid A protein in acute phase plasma high density lipoprotein the precursor of AA amyloid fibrils? AB - Serum amyloid A protein (SAA), an apolipoprotein of high density lipoprotein (HDL), is generally considered to be the precursor of AA protein, which forms the fibrils in reactive systemic amyloidosis in man and animals. This view is based on amino acid sequence identity between AA and the amino-terminal portion of SAA. However, in extensive and well-controlled studies of experimentally induced murine AA amyloidosis, we were unable to demonstrate a direct precursor-product relationship between SAA, in SAA-rich HDL preparations from acute phase or amyloidotic mouse or human serum, and AA protein in the amyloid deposits. This raises the possibility that SAA in its usual form, as an apolipoprotein of HDL synthesized during the acute phase response, may not be the major precursor of AA fibrils. The amyloidogenic forms of circulating SAA molecules may not be isolated during the preparation of HDL. Alternatively, particularly in the light of recent evidence that SAA mRNA is expressed in many different tissues throughout the body of appropriately stimulated animals, amyloidogenic SAA may be derived from sources other than the liver cells in which SAA-rich HDL is synthesized. PMID- 3105938 TI - Neutrophil-mediated tumor cell destruction in cancer ascites. II. A OK-432 attracts killer neutrophils through activation of complement C5. AB - When a streptococcal preparation, OK-432, was administered intraperitoneally to patients with malignant ascites, the number of neutrophils with cytotoxic activity against tumor cells was increased in the peritoneal cavity immediately after the OK-432 injection. In order to investigate the underlying mechanisms of such neutrophil accumulation, a possible neutrophil chemotactic activity in ascitic fluid was assayed by a modified Boyden method. The chemotactic activity for neutrophils was found significantly higher 6 hr after the OK-432 injection. OK-432 along had no direct chemotactic activity for neutrophils. The chemotactic activity was generated in vitro when ascitic fluid from patients without OK-432 treatment was incubated with OK-432 for 30 min at 37 degrees C. However, preheating of the fluid at 56 degrees C for 30 min or the addition of EDTA to the fluid resulted in the failure of generation of the chemotactic activity after the incubation with OK-432. The addition of EGTA did not show a significant effect. The chemotactic activity in ascitic fluid was found near cytochrome c marker (MW 12,400 D), when fractionated by Sephadex G-200 gel chromatography. The chemotactic activity was heat stable, nondialyzable, and neutralized completely with anti-human complement C5 antibodies. These results suggest that C5a generated via the alternative pathway activated by OK-432 may be responsible for the infiltration of killer neutrophils in the peritoneal cavity in patients with malignant ascites when they are treated by the intraperitoneal injection of OK 432. PMID- 3105939 TI - Plasma interleukin 2 receptor levels in renal allograft recipients. AB - Shed/soluble interleukin 2 receptor (IL2R) was measured by an enzyme-linked immunosorbent assay (ELISA) in serial samples of plasma from 32 patients with renal allografts. Patients on chronic dialysis (pretransplant) had elevated IL2R levels which fell toward normal after transplantation. Patients with acute rejection and viral infection had significantly higher levels of plasma IL2R than did patients with stable renal function or with cyclosporine nephrotoxicity (all P less than 0.005). Acute renal failure from other causes (renal artery stenosis, hemolytic-uremic syndrome) did not have a comparable rise in IL2R. The assay of shed/soluble IL2R may have diagnostic value in the clinical management of allograft recipients, a possibility that deserves further clinical evaluation. PMID- 3105940 TI - Effect of sodium cromoglycate on an experimental model of IgA nephropathy. AB - Recently, we reported on an experimentally-induced model of IgA nephropathy in mice, in which the lesions were very similar to those found in human IgA nephropathy. This model was achieved by long-term oral immunization and intravenous injection of colloidal carbon in order to achieve reticuloendothelial (RES) dysfunction. In this paper, we investigated the effects of sodium cromoglycate (SCG), an anti-allergic agent, on this model. Mice were treated with a small amount of colloidal carbon three times to block the RES, in addition to receiving oral administration of lactalbumin, as a food antigen. Open renal biopsy was performed at 18 weeks after the RES blockade, and mice were divided into 2 groups. One group received orally administered SCG and lactalbumin [SCG(+)], and the other group received lactalbumin only [SCG(-)] from 19 to 30 weeks. At 30 weeks, all mice were sacrificed for histopathological observation of renal tissue and blood sampling. IgA nephropathy had developed in all mice of the SCG(-) group, but had not developed in 7 out of the 9 mice in the SCG(+) group, at 30 weeks. Serum IgA levels obtained on sacrifice were significantly higher in the SCG(-) group. It was concluded that SCG effectively inhibited, not only the onset, but also the progression of IgA nephropathy in our original model. The effective mechanisms of this drug may act to suppress the local immunity produced through sensitization of gastrointestinal mucosa by food antigens. PMID- 3105941 TI - Topographic distribution and severity of brain lesions in Wernicke's encephalopathy. AB - The distribution and severity of the brain lesions were studied in 45 cases (age range: 26-84 years) of Wernicke's encephalopathy. The process was acute or subacute (active) in 24 cases and chronic (inactive) in 21. Cases with acute and subacute disease had more extensive and severe lesions than the chronic ones. The majority of the acute cases had lesions involving the mammillary bodies and thalamus and the subependymal structures along the third and fourth ventricles and the aqueduct. Only three acute cases had lesions restricted to the mammillary bodies. Among the chronic cases, the majority of the lesions were restricted to the mammillary bodies and the thalamus. Only two lesions extended as far down as the inferior collicles. Eleven out of 21 chronic cases has isolated lesions of the mammillary bodies. The affection of the mammillary bodies in chronic cases varied from barely visible to subtotal destruction of the tissue. Similarly, the lesions in the thalamus varied from slight gliosis in the dorsomedial nucleus to extensive nerve cell loss in several nuclei. There were similar variations in the severity of the clinical picture. Memory loss was recorded in three cases with isolated lesions of the mammillary bodies. PMID- 3105942 TI - [A mitochondrial encephalomyopathy: a case of a defect of complex I in the electron transport chain]. PMID- 3105943 TI - [A case of epilepsia partialis continua associated with nonketotic hyperglycemia due to steroid-induced diabetes mellitus]. PMID- 3105944 TI - Intra-arterial vasodilator agents to reverse human finger vasoconstriction. AB - Persistent vasospasm of the digits is difficult to attenuate or reverse. We studied the effect of intra-arterial nitroprusside on humoral and neurogenic digital vasoconstriction. Fingertip blood flow (FBF) was measured by venous occlusion plethysmography and capillary flow (CF) by the disappearance rate of a local injection of radioisotope. Small doses of nitroprusside (1 to 2 micrograms/min) increased FBF in fingers vasoconstricted by intra-arterial norepinephrine (4.7 +/- SE 1.7 to 38.4 +/- 26 ml min-1 100 ml-1 of tissue). Large doses of nitroprusside (up to 40 micrograms/min) did not increase FBF (11.8 +/- 6.0 ml to 6.6 +/- 3.9 ml) in fingers vasoconstricted by sympathetic nerve stimulation (body cooling). Forearm blood flow was measured in six subjects in the cool room and all showed an increase in flow with nitroprusside (6.7 +/- 1.1 ml to 26.0 +/- 6.0 ml), demonstrating that effective doses were used. Nitroglycerin (2.5 to 5 micrograms/min) significantly increased FBF from 5.1 +/- 1.9 ml to 14.8 +/- 6.9 ml as did phentolamine (50 to 100 micrograms/min) from 6.7 +/- 2.8 ml to 36.0 +/- 11.3 ml in sympathetically vasoconstricted subjects. Only phentolamine increased CF significantly (0.8 +/- 0.2 ml to 2.8 +/- 0.6 ml). Nitroprusside is an effective vasodilator for humorally induced vasoconstriction, but sympathetic digital vasoconstriction is resistant to nitroprusside and nitroglycerin is less effective than phentolamine. Phentolamine is the preferred agent because it increased FBF and CF. PMID- 3105945 TI - [Value of leukocyte and gallium scintigraphy in the differential diagnosis of splenic abscess/-infarct]. AB - The authors describe the limited role of non-invasive imaging procedures in the differential diagnosis of splenic abscess versus infarction. Sonography and computed tomography often do not offer any characteristic findings in these splenic disorders. A case is reported as an example. By means of 111 In-labelled leukocyte and gallium-67-scintigraphy exclusion of acute inflammatory processes can be performed with great certainty, and unnecessary surgical interventions can thus be avoided. PMID- 3105946 TI - Gartner's duct associated with diverticulosis of the fallopian tubes. AB - Hysterosalpingography demonstrated unilateral opacification of Gartner's duct and bilateral diverticulosis (salpingitis isthmica nodosa) of the fallopian tubes. An association of two mesonephric abnormalities in the same patient is postulated. The case also serves as a reminder of the association of diverticulosis with tubal ectopic pregnancy and infertility. PMID- 3105947 TI - The role of exercise testing in pulmonary diagnosis. AB - Exercise stresses the body's functional reserves that allow for the increased metabolic work and gas transport necessary for the efficient production of energy with physical activity or stress. Disease that reduces reserve in the gas transport organs will produce exertional symptoms not present at rest. Exercise testing has been well established in the evaluation of healthy persons and cardiac patients who are limited by cardiac or peripheral muscle function. For patients with lung disease, however, whose exercise performance is limited by reduced ventilatory capacity and disordered gas exchange, principles of exercise testing (and training) are different. In the evaluation of pulmonary patients, exercise testing can be used to measure exercise tolerance, assess the limitation to exercise in patients with unexplained dyspnea, evaluate patients for respiratory disability, assess blood gas changes with exercise, and detect exercise-induced asthma. Nevertheless, our understanding of the role of exercise in pulmonary diagnosis is at an early stage of development and much needs to be learned about the practical applications of exercise testing in the diagnosis, staging, and serial evaluation of pulmonary diseases. PMID- 3105948 TI - Determination of the effect of antimicrobics in combination against Listeria monocytogenes. AB - The in vitro activity of selected penicillins, extended spectrum cephalosporins, vancomycin, gentamicin, erythromycin, tetracycline, rifampin, and trimethoprim and sulfamethoxazole (alone and in combination) was determined by microtiter technique for 20 isolates of Listeria monocytogenes. The activity of selected combinations of antimicrobics was determined by the microtiter checkboard technique. Trimethoprim-sulfamethoxazole (1:20 ratio) was the most active agent in inhibitory tests and also showed bactericidal activity. The combinations of gentamicin with either ampicillin or vancomycin and that of erythromycin with tetracycline showed bactericidal effect in synergy studies. Combining ampicillin with an extended spectrum cephalosporin showed no antagonism, whereas, combining rifampin with trimethoprim or with trimethoprim/sulfamethoxazole led only to indifference or antagonism. These observations may have importance in selection of therapy in animal models or in selected clinical situations. PMID- 3105949 TI - Role of Chlamydia trachomatis and Mycoplasma pneumoniae in acute pharyngitis in children. AB - In a group of children with acute, nonstreptococcal pharyngitis, only one (2%) of the 44 children tested showed serologic or direct-immunofluorescence evidence of a recent Chlamydia trachomatis infection. Only two (5%) of the 43 children tested showed serologic evidence of a recent Mycoplasma pneumoniae infection. Neither C. trachomatis nor M. pneumoniae appears to be an important cause of acute pharyngitis in children. PMID- 3105950 TI - Antiarrhythmic agents for chronic ventricular arrhythmias. AB - A vast array of new antiarrhythmic agents have joined the old agents among the clinician's available resources. While treatment of ventricular arrhythmias is completely justifiable for patients with symptoms, their use to prevent sudden cardiac death has not yet been established. Because of their potential risks, the benefit/risk ratio must always be kept in mind. If we elect to treat patients who have benign or potentially lethal ventricular arrhythmias (usually to eliminate refractory symptoms) we typically begin with either a beta blocker or one of the new potent class IC antiarrhythmic agents such as flecainide or encainide. These drugs cause few side effects, no organ toxicity, and in the case of encainide or flecainide, have marked potency. Few important proarrhythmic effects are seen with these potent drugs in this group of patients. If these fail, one can try either a class IA or IB agent or a combination of a IA and IB agent. We always avoid amiodarone. In patients with lethal ventricular arrhythmias, one should choose a drug without negative inotropic potential such as quinidine or encainide as initial therapy. The combination of IA and IB agents should also be considered early in therapy. In patients with overt congestive heart failure with markedly depressed left ventricular function in the setting of lethal arrhythmias, disopyramide, beta blockers, and flecainide should be avoided. Amiodarone is used in this population only when the other available agents have proven to be ineffective or badly tolerated. PMID- 3105951 TI - Economic appraisal of preventive dental techniques. AB - In this paper the principles and particular problems involved in applying economic appraisal to the evaluation of preventive dental care are investigated. There is no cost benefit analysis in the existing literature which gives a reliable indication of the relative efficiency of preventive and restorative dental techniques. This is because of difficulties involved in trying to attach monetary values to the benefits of programmes which are publicly provided. These difficulties are not resolved by representing the benefits of prevention by restorative costs averted. Although cost effectiveness analysis may seem a more straightforward method, it suffers from the inappropriateness of the dmft (or dmfs) statistic for measuring the relative effectiveness of restorative and preventive treatments. An alternative measure of dental health outcome is suggested which encompasses aspects of the quantity (in life years) and quality of teeth produced by restorative and preventive care. The full potential of economic appraisal of preventive dentistry will be realised only if such comprehensive measures of dental health outcome are produced. The task of producing such measures should involve dentists, consumers of dental care and health care researchers. PMID- 3105952 TI - Localization of Rh1(D), 2(C), 3(E), 4(c), 5(e) and 25(LW) antigens of human Rh blood groups in fetal erythrocyte membranes. AB - The fetal erythrocyte membranes were partially solubilized with Triton X-100 at the low concentration (0.5%). The localizations of Rh1(D), 2(C), 3(E), 4(c), 5(e) and 25(LW) were investigated. Using hemagglutination inhibition assay, Rh1(D) antigen activity was observed in the Triton-treated membrane (Triton shell) containing mainly band 1, 2 (spectrin), band 5 (actin), band 4.1 and a part of band 3, while Rh2(C), 3(E), 4(c), 5(e) and 25(LW) antigens were detected in the supernatant containing band 3, 6, 2.2, 2.3 and 4.2. It is suggested that: Rh1(D) antigen would associate with cytoskeleton matrix of fetal erythrocyte membranes; Rh1(D) and Rh25(LW) antigens might be integral membrane proteins, while Rh2(C), 3(E), 4(c) and 5(e) antigens would be surface membrane proteins which are easily released from membranes by EDTA, mercaptoethanol and alkaline treatments. PMID- 3105953 TI - Interspecies differences in rhodanese (thiosulfate sulfurtransferase, EC 2.8.1.1) activity in liver, kidney and plasma. AB - Rhodanese levels have been measured in liver, kidney and plasma from a number of species. Liver activity was low in marmosets, pigeons and beagle bitches. Levels were high in rats and somewhat lower in hamsters and guinea pigs while levels in two strains of rabbits were intermediate between guinea pigs and marmosets. The relationship between hepatic and plasma rhodanese and cyanide sensitivity is discussed. PMID- 3105954 TI - C3-like activity in C3-deficient dog serum. AB - A complete absence of the third component of complement has been demonstrated in a colony of Brittany spaniels. The deficiency is inherited in an autosomal recessive fashion and is clinically characterized by an increased susceptibility to infection and renal disease. Despite having no detectable antigenic C3, C3 deficient dog serum has approximately 10% of normal serum C3 hemolytic activity. This report characterizes the nature of the C3-like activity in C3-deficient dog serum. The activity is inhibited by heating serum to 56 degrees C for 30 min and by incubation in 0.01 M EDTA. The activity is also sensitive to both methylamine and D-76, in a dose-dependent fashion. The lytic activity in C3-deficient dog serum appears to be complement mediated. Furthermore, lysis of EAC1,4,oxy2 cells by deficient dog serum is inhibited by methylamine. Although lysis is boosted by the addition of purified C5, a greater boost is obtained in the absence of methylamine. Therefore, there exists a methylamine-sensitive protein other than C4 in C3-deficient dog serum which interacts with C5. It is possible that this protein may be a newly discovered complement protein for which appropriate conditions for its detection have not previously been available. PMID- 3105955 TI - Paediatric nursing: home healing. PMID- 3105956 TI - Use of fine needle aspiration biopsy in differential diagnosis between nephrotoxicity and rejection. PMID- 3105958 TI - Comparison of arterial blood gas with continuous intra-arterial and transcutaneous PO2 sensors in adult critically ill patients. AB - We compared the partial pressure of oxygen directly via a continuous intra arterial probe (PiaO2) and indirectly using a transcutaneous device (PtcO2) with simultaneously obtained arterial blood PaO2. The PiaO2 values were measured using a bipolar oxygen sensor placed through an 18-ga arterial catheter. The PtcO2 values were measured using a transcutaneous O2-CO2 sensor placed on the abdomen. Seven critically ill, hemodynamically stable, ventilator-dependent adult patients were studied. Measurements were obtained at varying concentrations (0.25 to 1.0) of inspired oxygen after a 10-min stabilization. A total of 78 simultaneous values were obtained; by linear regression: PiaO2 = 0.91 PaO2 + 1.39 (r = .98, standard errors of the estimate [SEE] = 18.6); PtcO2 = 0.39 PaO2 + 36.2 (r = .89, SEE = 14.1). To assess these instruments as trend monitors, we compared the changes in simultaneous PaO2, PiaO2, and PtcO2 values; by linear regression: delta PiaO2 = 0.90 delta PaO2 + 3.88 (r = .96, SEE = 27.7); delta PtcO2 = 0.43 delta PaO2 + 5.6 (r = .94, SEE = 15.2). We conclude that, although these instruments correlate highly with the PaO2, the SEE was substantial and therefore may limit their clinical reliability in adults. Any acute or clinically significant change in PiaO2 or PtcO2 should be confirmed with a blood gas PaO2. PMID- 3105957 TI - Clinical results of ciclosporin-prednisone therapy in renal transplantation. PMID- 3105959 TI - Hypoalbuminemia as an indicator of diarrheal incidence in critically ill patients. AB - Recently, we noted that substantial numbers of critically ill patients admitted to a medical ICU developed diarrhea. We checked them for infectious, metabolic, and untoward medication effects, which were negative. We next considered a possible causal relation between reduced serum albumin and diarrhea. To document the frequency of diarrhea in this population, explore the relation between hypoalbuminemia and diarrhea, and make a preliminary assessment of a peptide based, chemically defined diet in these catabolic patients, a study of consecutive medical ICU patients was begun. For each patient, we recorded the principal diagnosis, type of diet received, the frequency and volume of stool, and the serum albumin concentration at admission. When diarrhea developed, attention was paid to the serum albumin levels as well as the effects of various diets. Overall, 12 (34%) of 35 study patients developed diarrhea. No patient had a previous history of diarrhea, malabsorption, weight loss, or GI symptoms that may precede the onset of diarrhea. The stools from each patient with diarrhea were examined for enteric pathogens, ova and parasites, Clostridium difficile culture and cytotoxin assay, and qualitative stool fat, which were all negative. Every patient with a serum albumin level less than 2.6 g/dl developed diarrhea. No patient with a serum albumin level of 2.6 g/dl or greater developed diarrhea, regardless of the type of nutritional support received. Four of the 12 patients with hypoalbuminemia and diarrhea were placed on a peptide-based, chemically defined diet, after which their diarrhea resolved and their serum albumin concentrations increased. PMID- 3105960 TI - Venous hypercarbia in canine hemorrhagic shock. AB - The venous-arterial PCO2 gradient may increase in certain low-flow states, such as CPR and canine endotoxemia. To determine whether venous hypercarbia also occurs in hemorrhagic shock, we studied 12 anesthetized, mechanically ventilated dogs. We performed laparotomies on the animals, inserting catheters into their renal, superior mesenteric, and external iliac veins. Flow in the corresponding arteries were determined using electromagnetic flow probes. The dogs were randomized into a control group (n = 6), and a hemorrhagic shock group (n = 6) which was bled to a mean arterial pressure of 45 to 50 mm Hg and maintained at this pressure for the 6-h study. The results demonstrated a significant (p less than .05) increase in lactate and venous-arterial PCO2 gradient systemically and in all three regional beds. A significant decrease of venous blood pH accompanied these changes which are consistent with our previous findings in low-flow, canine endotoxemia. We conclude that venous hypercarbia is a nonspecific phenomenon, common to low-flow states. The increased CO2 represents both an increased CO2 production and a decreased removal, secondary to low-flow. PMID- 3105961 TI - Propylene glycol intoxication and nitroglycerin therapy. PMID- 3105962 TI - Thyrotropin releasing hormone: effects in monkeys and dogs subjected to experimental circulatory shock. AB - We tested the hypothesis that thyrotropin releasing hormone (TRH) would improve cardiovascular function and survival in circulatory shock by opposing the adverse effects of endogenous opioids and other pathophysiologic mediators. Cynomolgus monkeys and mongrel dogs were anesthetized and catheterized to measure mean arterial pressure (MAP) and left ventricular contractility (LV dp/dtmax). Hemorrhagic shock was induced by bleeding into a reservoir to achieve and maintain MAP at 45 mm Hg for one hour. Endotoxic shock was produced by the iv injection of an LD80 dose of Escherichia coli lipopolysaccharide endotoxin (3 mg/kg in dogs and 5 mg/kg in monkeys). Animals were treated iv with either TRH (2 mg/kg plus 2 mg/kg X h) or equivolume saline. TRH significantly increased MAP and LV dp/dtmax in primate hemorrhagic and endotoxic shock. In primate hemorrhagic shock, TRH significantly (p = .02) improved survival (alive/total = 4/5 vs. 0/5). However, TRH had no effect on survival in endotoxemic primates. In contrast, TRH treatment in dogs produced only a transient hemodynamic response after endotoxemia and no significant hemodynamic effect after acute hemorrhage (even at twice the TRH dose). TRH did not affect survival in either dog model of circulatory shock. Based on extensive evidence with the opiate receptor antagonist naloxone in other studies, endogenous opioids play a role in the cardiovascular depression in primate and canine circulatory shock. From these studies with TRH, we conclude that TRH is relatively ineffective in canine circulatory shock, and physiologic antagonism of the adverse effects of opioids and other cardiodepressant substances by TRH administration may prove to be a useful alternative treatment of primate hemorrhagic shock. PMID- 3105963 TI - Factors affecting ascorbate oxidation in aqueous humor. AB - Aqueous humor from human glaucomatous eyes was divided into two groups. Group I aqueous humor contains a negligible amount of ascorbate, while group II contains ascorbate. Group I aqueous humor stimulates ascorbate oxidation. This oxidative effect is inhibited by the addition of EDTA, indicating the presence of metallic ions. The amount of copper determined by atomic spectrophotometry in these samples was 1.54 micrograms/ml. On the contrary, group II aqueous humor protects against ascorbate oxidation. The small amount of albumin present in these samples accounts for part of this protective effect. PMID- 3105964 TI - New anticonvulsants in pediatrics: carbamazepine and valproate. AB - The majority of patients with epilepsy have their first seizure during childhood and are first evaluated and diagnosed by their pediatrician. For many patients the medication selected by the pediatrician will be taken for an extended time period, perhaps even for a lifetime. The first job of the pediatrician is to be sure that the patient's recurrent attacks represent genuine epilepsy and not some other paroxysmal medical disorder such as migraine or cardiac arrhythmias. Epileptic seizures are then classified by a careful clinical description of the attacks in conjunction with the results of the physical and EEG examinations. Based on all of the information at hand, the clinician chooses the drug that is most likely to reduce or eliminate further seizures without exposing the child to unnecessary medical risk or behavioral-cognitive adverse effects. In properly selected patients, both carbamazepine and valproate are safe, physically well tolerated, and less likely to provoke chronic mental side effects than the pediatrician's "traditional" choices: phenobarbital or phenytoin. Although carbamazepine and valproate have been widely acclaimed by neurologists and epileptologists, practicing pediatricians have heretofore been less likely to initiate treatment with these drugs. Yet pediatricians have something of priceless value to offer the child with epilepsy: seizure control and a clear mind. The information in this monograph should assist the practicing pediatrician in the rational choice, initiation, and follow-up of treatment with these two excellent anticonvulsants. PMID- 3105965 TI - Endobronchial tuberculosis. Serial fiberoptic bronchoscopy and natural history. AB - Endobronchial tuberculosis in the preantibiotic era was considered a complication of advanced post-primary disease. Bronchial mucosa adjacent to parenchymal cavities was bathed in infectious sputum, resulting in implantation. Effective antituberculosis drug therapy has reduced childhood exposure, resulting in an increase in adult primary tuberculosis with unusual clinical and roentgenographic presentations. We studied four adults with endobronchial tuberculosis who presented with unusual lobe involvement mimicking bronchogenic carcinoma. Fiberoptic bronchoscopy illustrated the range of endobronchial appearances, including evolution of mucosal ulcer to hyperplastic polyp and bronchostenosis. Complete fibrostenosis with lobar atelectasis was observed in one patient, and an eroding tuberculous lymph node in another. In the current era, endobronchial tuberculosis is more likely to be discovered in adults with progressive primary tuberculosis who have non-cavitary lower lung field infiltrates. Bronchial mucosal ulceration can result from submucosal lymphatic spread of organisms from adjacent parenchymal disease, as well as implantation. PMID- 3105966 TI - Primary pulmonary hypertension. Length of survival in patients referred for heart lung transplantation. AB - The paucity of data on the natural history of primary pulmonary hypertension (PPH), and the observation that some patients awaiting heart-lung transplantation (HLT) appeared to be living longer than expected, led us to analyze the survival data of patients with PPH who had been referred for consideration of HLT. Ninety patients (female: male = 3.6:1) met clinical and hemodynamic criteria for PPH. Age at diagnosis was 29.8 +/- 7.9 years (mean +/- SD) (range 13-48 years). Symptom duration was 65.9 +/- 47.4 months, while survival from diagnosis was 42.9 +/- 42.6 months, giving a mean lead time of 23 months. Mean pulmonary artery pressure (PAP) at diagnosis was 61.6 +/- 15.0 mm Hg. The incidence of patent foramen ovale (PFO) was 19 percent, postpartum onset 16 percent, family history 6 percent, and cirrhosis 3 percent. The survival of 27 patients who died without operation was 50.3 +/- 52.5 months (median 37 months), with a symptom duration of 68.4 +/- 57.5 months (median 64 months). Both a high mean right atrial pressure (RAP) (p less than 0.025) and high mean PAP (p less than 0.025) correlated inversely with survival. For the whole group, none of the variables, age at diagnosis, sex, mean PAP or mean RAP at diagnosis, symptom duration prior to diagnosis or the presence of a PFO, postpartum onset or positive family history, significantly influenced survival. However, a low cardiac output (p less than 0.05) adversely influenced prognosis. The discrepancy between the mean and median length of survival in our group and previous reports confirms the need for further clarification of natural history and for appropriate clinical trials to assess therapeutic endeavors. PMID- 3105967 TI - Ventilation-perfusion inequality in lung disease. PMID- 3105968 TI - Difluoromethylornithine enhances the uptake of methylglyoxal-bis(guanylhydrazone) prior to inhibiting leukemic cell proliferation. AB - Difluoromethylornithine (DFMO) is a nonreversible inhibitor of ornithine decarboxylase (ODC), the initial rate-limiting enzyme in the polyamine biosynthetic pathway. When HL60 leukemic cells were incubated in the presence of concentrations of DFMO from 0.05 mM to 5 mM, there was a concentration-dependent inhibition of ODC activity apparent within 24 h. Likewise, cellular polyamine levels were reduced by the presence of DFMO in a concentration-dependent manner after 4 days. The growth of cells incubated with 0.5 mM or greater was inhibited after 3-4 cell doublings. When the concentration of DFMO was less than 0.5 mM, growth was not inhibited. Methylglyoxal-bis(guanylhydrazone) (MGBG) uptake was enhanced in cells treated with concentrations of 0.05-0.5 mM DFMO, but not enhanced in cells treated with DFMO concentrations of 1 mM or greater. DFMO induced cellular polyamine depletion does enhance MGBG uptake into HL60 cells, but treatment with high concentrations of DFMO, which deplete polyamines to the extent that growth is inhibited, negate this effect. PMID- 3105969 TI - Comparative efficacy of praziquantel and its optic isomers in experimental therapy of schistosomiasis japonica in rabbits. PMID- 3105970 TI - Free jejunal graft for reconstructing the pharynx and cervical esophagus. PMID- 3105971 TI - Effects of wrapped supine, unwrapped supine and prone positions on transcutaneous oxygen tension in neonatal pneumonia. PMID- 3105972 TI - Significance of low levels of blood and hair selenium in dilated cardiomyopathy. PMID- 3105973 TI - Ultrastructural investigation of osteogenic cells. PMID- 3105974 TI - Intrahepatic cholestasis of pregnancy and its complications. Analysis of 100 cases in Chongqing area. PMID- 3105975 TI - Investigations on the prevalence, immunodiagnosis and experimental model of giardiasis. PMID- 3105976 TI - Nasal mucociliary function in normal adults and different nasal diseases. PMID- 3105977 TI - Risk factors in postoperative wound infection. PMID- 3105978 TI - Effects of aging on airway hyperreactivity in normal persons. PMID- 3105979 TI - Isolation of Toxoplasma gondii from a disomus with hydrocephalus in the Beijing area. PMID- 3105980 TI - Thrombophilia caused by primary antithrombin-III deficiency. Report of an autopsy case. PMID- 3105981 TI - [The effect of cryosurgery on premalignant lesions of hamster cheek pouch mucosa]. PMID- 3105982 TI - [Image patterns of the cervical spine on the CT-scan]. PMID- 3105983 TI - [The effect of sodium crompromate in preventing exercise-induced asthma]. PMID- 3105984 TI - Current status of aldose reductase inhibitors. PMID- 3105987 TI - [Clinical trial of UFT in malignancies--an analysis of 337 patients. Co-operative Group for Clinical Study of UFT]. AB - Clinical phase II trial of UFT (4:1 mixture of 5-Fu and FT-207) prepared by Jinan Pharmaceutical Company was carried out cooperatively from 1984-1985. In 337 patients treated, 289 received UFT alone. The drug contains 50mg FT 207 per tablet. The dose given was #4, T. i. d. The total dose ranged from 8.4 g to 75.5 g in 6-8 weeks, majority of patients received 20-40 g. Complete remission was obtained in 7 patients (2.4%), while partial remission in 65 (22.5%), stable in 158 (54.7%) and progression in 59 (20.4%). Data showed that favorable results were observed in stomach cancer, esophageal cancer, rectum and colon cancer, and breast cancer. Excellent results were obtained in nasopharyngeal cancer with UFT in combination with irradiation. The gastro-intestinal tract reaction was mild, and bone marrow depression was observed in less than 15% of all patients treated. In conclusion, UFT may become an useful means in the management of common malignancies. PMID- 3105986 TI - Comparison of efficacy of human and porcine insulin in treatment of diabetic ketoacidosis. AB - The efficacy of semisynthetic human insulin (HI) and monocomponent porcine insulin (PI) in treatment of diabetic ketoacidosis (DKA) was compared in 10 (PI) and 11 (HI) patients in a double-blind randomized study. Insulin (8 U/h i.v.), fluid replacement (0.65% NaCl and 5% glucose), and KCl supplements were administered according to a fixed protocol. Glucose, potassium, sodium, creatinine, calcium, phosphate, and free-insulin concentrations were never significantly different during the study. At the start, mean +/- SD of pH was 7.10 +/- 0.14 in the HI group and 7.10 +/- 0.12 in the PI group. The time to reach arbitrary values for pH, bicarbonate, base excess, and beta-hydroxybutyrate was shorter during HI treatment, but the differences were not statistically significant. During HI treatment, the arbitrary value of 1.0 mM of acetoacetate was reached faster than during PI treatment (5.2 +/- 2.6 and 8.4 +/- 0.9 h, respectively; P less than .05). The concentration of acetoacetate was significantly different between the two groups after 6 and 7 h of insulin treatment (6 h: HI 0.82 +/- 0.50 mM and PI 2.19 +/- 1.65 mM, P less than .05; 7 h: HI 0.51 +/- 0.40 mM and PI 1.74 +/- 1.54 mM, P = .05). We conclude that recovery from DKA during treatment with HI might be slightly faster than during treatment with PI. If this difference is real, it does not seem clinically important. PMID- 3105985 TI - Risk of ketosis during intensive insulin therapy in pre-school-age diabetic children. AB - The risk of ketosis and its relationship to the mode of insulin therapy were studied in a subset of pre-school-age diabetic children. These five children, who initially responded poorly to standard in-hospital diabetes management, were selected for a program of intensified therapy directed at achieving more stable blood glucose control. Optimized conventional therapy was first employed for 16 +/- 5 mo and did not improve substantially blood glucose level or stability. During this period, there was an average of almost one episode of ketonuria per patient per month, and three diabetic ketoacidosis episodes were observed. Because of its limited efficacy, the treatment was then changed to continuous subcutaneous insulin infusion. This mode of therapy had a rapid favorable effect on blood glucose control, with no concomitant increase of the frequencies of ketonuria or diabetic ketoacidosis, most of which occurred during the first months of insulin pump therapy. Deliberate cessation of either conventional or subcutaneous insulin infusion therapy for 7 h under close in-hospital control resulted in similar metabolic changes: a slight nonconstant increase of blood glucose, and an abrupt rise of blood 3-hydroxybutyrate to 3 mM, with massive ketonuria. The management of these young diabetic children with insulin pump therapy was thus not associated with an increased frequency or an accelerated rate of development of ketosis. However, the possible failures originating from the infusing device and the rapid increase of ketosis in young ages require special vigilance from the parents, based on twice-daily urine testing for ketones and appropriate insulin supplementation. PMID- 3105988 TI - Plasma and testicular testosterone in experimental diabetic rats. AB - Testicular and plasma testosterone levels were found to be decreased markedly in streptozotocin diabetic rats compared with those of controls. Treatment with 6 units NPH insulin daily for one week almost normalized plasma testosterone levels parallel to the increase in body and liver weights in diabetic rats, while testosterone levels in testicles were not significantly changed. Plasma prolactin and LH levels were unchanged among control, diabetic and diabetic insulin-treated rats. Thus, testosterone reduction in the testis might play a role in diabetic impotence. PMID- 3105989 TI - [Fine structure of the nucleus of the parasitic flagellate Trypanoplasma borreli (Kinetoplastida) in the interphase and mitosis]. PMID- 3105990 TI - Structure-metabolism relationships (SMR) for the prediction of health hazards by the Environmental Protection Agency. II. Application to teratogenicity and other toxic effects caused by aliphatic acids. PMID- 3105991 TI - I.v. infusion devices: are they always justified? AB - Electronic infusion device (EID) use is increasing and contributes substantially to hospital costs, approximately $1,000,000 per year at the University of Michigan Hospitals. Only two studies have been conducted with the purpose of determining potential advantages of EID over less-expensive roller clamps. Neither clearly demonstrated that controllers are more beneficial than roller clamps. Pumps have not received this type of study. EID use should, therefore, be limited only to those situations in which they are decidedly advantageous. PMID- 3105992 TI - Economic examination of cefoperazone therapy. AB - Medical records of 1137 patients from 35 hospitals were reviewed to examine the total cost of care for patients receiving cefoperazone as initial therapy compared to a control group receiving alternative agents. The direct costs of care measurable through a retrospective review of patient records were examined, including the cost of antibiotic acquisition, drug administration, laboratory testing, and room and board. Results of a regression analysis show that cefoperazone as initial therapy is associated with lower costs for all factors studied except acquisition cost. Antibiotic acquisition averaged $24 per patient more for the cefoperazone group (p less than 0.01). However, for cefoperazone patients drug administration was $63 less (p less than 0.0001), laboratory testing costs averaged $9 less (p = 0.22), and costs associated with room and board charges were $80 less (p = 0.40). Total costs averaged $3073 per cefoperazone patient and $3228 per control patient (p = 0.20). These data suggest that the previously accepted definitions of antimicrobial costs (i.e., cost per gram, cost per dose, cost per day) may no longer be adequate in this era of cost containment. In order to make sound clinical decisions with lowest total costs, practitioners should identify how and where costs are incurred. PMID- 3105993 TI - Effect of retinol toxicity on hepatic S-adenosylmethionine-dependent transmethylation in rats. AB - Hepatic metabolism of the labile methyl group donor, S-adenosylmethionine (SAM), was investigated in rats fed toxic levels of retinol (1,000 IU/g of diet) since this treatment is known to decrease hepatic SAM concentration. The turnover rate of the hepatic SAM pool was not affected by the excess retinol, but the use of SAM as a labile methyl donor was restricted. Incorporation of the methyl group into phosphatidylcholine was reduced by 51% and oxidation of the methyl group to CO2 was decreased by 40%. In addition, the concentrations of cysteine and cystine, which are synthesized subsequent to demethylation of SAM, were reduced by 32% and 30%, respectively, in liver of high-retinol-fed rats, while methionine concentration was unchanged. The toxic level of dietary retinol may bring about a shift in the metabolism of SAM from transmethylation toward pathways that regenerate methionine via 5'-methylthioadenosine. PMID- 3105995 TI - [Meningoencephalitis caused by Brucella abortus infection]. PMID- 3105996 TI - [Lung injury following mitomycin C]. PMID- 3105994 TI - Effect of aluminum on the hepatic mixed function oxidase and drug metabolism. AB - The effect of aluminum injection on the hepatic mixed function oxidase was examined in male Wistar rats. A cannula was surgically implanted in both the control and aluminum treated animals to provide a common port for aluminum injection. In addition, the control animals were pair-fed to the aluminum treated animals. The treated animals accumulated aluminum at about 0.1 mg/gm dry weight of liver/day. At 14 days, the cytochrome P-450 was decreased 20%, but the other components, cytochrome b5 and cytochrome reductases, were unchanged. By day 21 both cytochrome P-450 and cytochrome b5 were reduced 25%. Although NADPH cytochrome c reductase was not affected, the other flavoprotein, NADH cytochrome c reductase, was reduced. Drug metabolism, O-demethylation of p-nitroanisole and p-hydroxylation of aniline, was not affected at 14 days. However, at 21 days O demethylation was not affected, but aniline hydroxylation was decreased, indicating an affect of aluminum on a specific isoenzyme of cytochrome P-450. Uniquely, the nonactivated glucuronyl transferase activity was fourfold greater in the aluminum treated animals. The increase was greater than cation activation and was similar to the detergent activated activity. Thus, aluminum infusion does produce specific alterations in microsomal function, including drug metabolism and conjugation. PMID- 3105998 TI - [Percutaneous gastrostomy]. PMID- 3105997 TI - [Diagnosis of growth hormone deficiency with the growth hormone releasing factor GRF 1-40. The potentials and limits]. AB - Eleven patients with constitutionally delayed development, seven patients with idiopathic growth hormone deficiency and ten patients with craniopharyngeoma received growth hormone releasing factor GRF 1-40 in a dose of 1 micrograms/kg body weight as a bolus injection. In the patients with constitutionally delayed development, a mean maximum HGH value of 86.7 microU/ml was measured 30 minutes after GRF injection. Considerably higher HGH stimulation values were thus obtained after GRF than with conventional stimulation methods. In the patients with idiopathic growth hormone deficiency or craniopharyngeoma, there was mostly only a slight rise of the growth hormone level with a delayed onset. Merely two patients with craniopharyngeoma could be adequately stimulated in accordance with conventional criteria (HGH greater than 12 microU/ml), although their values also remained markedly below those of the patients with constitutionally delayed development. Both patients had somatomedin C values which were below that normal for their age; together with the delayed rise in HGH after GRF, this allowed diagnosis of growth hormone deficiency. PMID- 3105999 TI - Iron deficiency. Misunderstood, misdiagnosed and mistreated. AB - Iron deficiency is a common medical problem that may present in a variety of ways to the general practitioner or the specialist. An understanding of iron physiology is relevant to diagnosis and treatment of iron deficiency. Human iron metabolism is a system based on conservation. For this reason, the most common cause of iron deficiency is loss of the normal conservation of iron and this usually means blood loss. The important implication is that the search for the cause of iron deficiency will usually focus on the gastrointestinal tract in males and non-pregnant, non-menstruating females. Iron deficiency is commonly misdiagnosed. The usual error is misinterpretation of the laboratory features of the anaemia of chronic disease. The serum iron is low, but the iron binding capacity is normal and ferritin is normal or high. There are problems and exceptions involved in interpretation of iron indices. Treatment of iron deficiency requires an understanding of iron absorption and the ability of the marrow to respond. In most circumstances, iron deficiency will respond to adequate doses of oral iron; however, there are a few situations when oral iron is unsuitable and parenteral iron is required. An inadequate response to iron may indicate inadequate supply of iron to the bone marrow (e.g. malabsorption, non compliance) or failure of the marrow to respond (e.g. concomitant folate deficiency). Pregnancy is a special situation in which conservation of iron is overcome by fetal iron requirements and in which application of the knowledge of iron physiology should be applied to prevent and treat iron deficiency. PMID- 3106000 TI - [Orthostatic tremor: clinical aspects, pathophysiology and therapy]. AB - Orthostatic tremor is characterized by its isolated occurrence in leg and trunk muscles during standing with undisturbed sitting, lying and walking. In a female patient with this tremor syndrome the basic electrophysiological feature of muscle activity was a 16 Hz, highly synchronized tremor in all leg muscles and sometimes in the arm muscles. This rhythmic EMG activity however, was not restricted to stance but occurred during all kinds of muscle activation in sitting, lying or standing positions, despite only standing was accompanied by a subjective sensation of unsteadiness and falling to the ground. Mechanical tremor analysis at the patella revealed an additional 8 Hz tremor caused by alternating large and small amplitudes of the 16 Hz tremor bursts. The occurrence of the 8 Hz tremor was much more related to the feeling of unsteadiness than the 16 Hz tremor. Single motor units mostly fired at a frequency of 8 Hz, but only at the time of tremor bursts. Hence the 16 Hz-pattern may not be explained as the result of a pure motoneuronal abnormality. There were no indications for abnormal reflexes contributing to tremor genesis. A fixed time relation of the tremor bursts in different muscles has been found suggesting a common generator within the CNS for the tremor. After successfully treatment with Primidon the pattern of muscle activation was normalized during sitting and lying, however, during standing and walking the 16 Hz tremor was still present. We believe that an unknown central oscillator is causing the tremor and central structures which are involved in stance regulation have a predominant access to switch on this oscillator. PMID- 3106002 TI - [Visual evoked potentials and hemispheric differences: on the functional significance of homologous regions]. AB - A total of 18 right handed subjects participated in an experiment, in which visually evoked potentials were recorded from four scalp electrodes (01, 02 and P3, P4) when words or flashes of diffuse light were presented as stimuli. The evoked potentials were subdivided into three components, an early component (Komp1, 0-150 ms) and two late components (Komp2, 150-300 and Komp3, 300-450 ms). For each of these components and for each subject, correlations were computed between different recording sites. The results show that homologous correlations (01:02, P3:P4) yield values, which are significantly higher than the values of the intra- (01:P3, 02:P4) and diagonal interhemispheric (01:P4, 02:P3) correlations. This result, which holds true for all of the three components in a similar way, is independent from the type of presented stimuli. In contrast to homologous correlations, intra- and diagonal interhemispheric correlations do vary as a function of stimulus type and different components as well. Here, the results show that the degree of correlation between different recording sites is positively related to the degree of cognitive load: with increasing cognitive load, the degree of synchronous neural activity increases. Homologous correlations are independent from the type of stimuli (words and pictures) and from the type of VEP-components (Komp1, 2, and 3) as well. Thus, it can be concluded that homologous correlations reflect attentional rather then cognitive processes. PMID- 3106001 TI - [Spectral analyses in ocular microtremor in disorders of brain stem function]. AB - In 61 healthy and 79 patients the small involuntary movements were recorded using a piezoelecric strain gauge transducer mounted on a modified optical frame. The recording was followed by a spectralanalytic process with special programs. We used a detailed neurological examination for estimating the clinical condition of the patients. The spectral analysis of the ocular microtremor supplies results which correspond to the clinical condition in each case of the patients with increased central herniation. A irreversible loss of cerebral function (brain death) can also be documented. Patients with special clinical syndromes show tremograms which answer the probably extent of damage of (meso-)pontine parts. We investigated and discussed effects of the influence of central-nervous drugs, age dependent relations, the significance of cardiovascular pulsations and questions and questions of the comparability of findings between both bulbi. The ocular microtremor shows burst-like components with a frequency peak between 60 and 90 oscillations per second. At present must be assessed that it could be a potential monitor of the function of the reticular (meso-)pontine formation. PMID- 3106003 TI - [Methodology and normal values in recording evoked motor potentials following transcranial stimulation in the human]. AB - Electric non-invasive stimulation of the motor cortex was performed in 19 healthy subjects. Muscle responses were recorded with surface electrodes from the abductor, pollicis brevis and anterior tibial muscle. The mean central motor latencies for pathways regulating the function of the upper limbs was 4.5 msec (standard deviation 0.5 msec), the corresponding latency for the lower limbs was 9.6 msec (standard deviation 1.2 msec). The reproducibility of latencies and configuration of the potentials obtained indicates that the method described can be used as a reliable method in the diagnosis of affections of the motor system. PMID- 3106004 TI - [Value of early acoustic and somatosensory evoked potentials in monitoring and prognostic assessment of coma in barbiturate therapy--comparison with clinical aspects and EEG]. AB - 25 comatose patients suffering from severe cerebral lesions of different etiology were examined during barbiturate-therapy by Glasgow-Pittsburg-Coma-Scoring-System (GPCS), EEG, somatosensory and brainstem acoustic evoked potentials. The findings were correlated in view of prognostic prediction and importance for monitoring. A modified form of the Glasgow-Outcome-Score (GOS; independent-survival, dependent survival, dead) was used for evaluating the outcome. In case of an initial GPCS less than 10 points none of the patients survived, in case of GPCS greater than 10 points 11 out of 19 patients survived. The latter relation of survival was also found in patients with improving or impairing scores during the observation period. In case of initial burst-suppression pattern in the EEG 7 out of 11 patients survived, in case of diffuse abnormalities with or with-out additional focal signs - 4 out of 10 patients survived, but in the latter there was none with an outcome of independent survival. All patients with an isoelectric EEG died. In case of bilateral recording of scalp- SEP 7 out of 11 patients survived, in case of unilateral loss of scalp-EP 4 out of 8 patients survived, but in the latter cases none with an outcome of independence. All patients with initial bilateral failure of scalp-SSEP or loss during the observation period died. In case of bilateral registrable BAEP (wave I to V) 11 out of 17 patients survived. All patients with initial uni- or bilateral failure of those potentials or loss during the observation period died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106005 TI - [Brain mapping--topographic demonstration of the EEG and evoked potentials in psychiatry and neurology]. AB - Brain mapping of EEG and evoked potentials permits the topographic display of electrical activity of the brain and is superior to conventional polygraphic procedures. Data from 16 scalp electrodes and two ear reference electrodes were worked up. The spontaneous EEG and the EEG during different testing conditions to activate particular brain regions was measured. 2 s EEG data segments were subjected to spectral analysis by a fast Fourier transformation (FFT). For late evoked potentials (VEP, AEP, SEP and P300) a single value representing the amplitude of EP at each 2-ms poststimulus latency point served for subsequent topographic mapping. Statistical techniques (Student's t-test) have been used in conjunction with EEG and EP data to render visible the regions where a clinical population differ from normal subjects. The results show abnormalities of EEG and EP in patients with psychical und neurological diseases. PMID- 3106006 TI - [Static NMR magnetic fields change somatosensory evoked potentials in the human]. AB - In strong static magnetic fields as used by NMR for clinical diagnosis we found oscillations in somatosensory evoked potentials of man when stimulating the Nervus medianus at the wrist joint. These new signals are to register only, when the head of the test person is inside of the magnetic field. A magnetic influence only of the stimulated arm has no effect of the normal SEP-signal. PMID- 3106007 TI - [Cortical distribution of 2 delta frequencies in slow wave sleep]. AB - Many persons show two different types of delta-activity during synchronized sleep; these can already be differentiated visually as follows: one is located over the anterior brain areas, has a high frequency and is monomorph, the other one is located over the posterior brain areas, has a low frequency and is polymorph. However, both rhythms overlap considerably regarding their cortical distribution. The high high frequency delta-activity usually ranges from 1.5-2.9 Hz with a maximum at 2Hz; the one with low frequency ranges from 0.1-1.4 Hz with a maximum at 0.9 Hz. The interhemispheric coherence of the delta-activities is high with 0.7-0.9; for the anterior regions it is slightly higher than for the posterior ones. The intrahemispheric coherence is low, as was to be expected, and it is less than 0.3. PMID- 3106008 TI - Corticoids modulate FSH action in cultured porcine granulosa cells. AB - The effect of corticosteroids on FSH-stimulated production of progesterone and on LH/hCG receptor binding of 125I-hCG were studied in immature porcine granulosa cells. Deoxycorticosterone, deoxycorticosterone-acetate (DOC), corticosterone, aldosterone and dexamethasone enhanced FSH stimulated progesterone production in a dose-dependent manner. In contrast, cortisol cortisone and tetrahydrocorticosterone did not affect progesterone production. delta 4 androstenedione did not alter the enhancing effect of DOC. Incubation of granulosa cells with dbcAMP caused no significant increase of progesterone synthesis. All corticosteroids tested markedly inhibited stimulation of 125I-hCG binding on granulosa cells by FSH. It was concluded that the modulatory effect of corticosteroids on ovarian responsiveness to FSH consists of direct action on granulosa cells. PMID- 3106009 TI - Biological activity of TRH thionalogue and its diastereoisomers. AB - Binding affinity and TSH-releasing activity of [Prot3] TRH analogue (L pyroglutamyl-L-histidyl-L-proline thioamide), TRH and their LDL and LLD diastereoisomers were compared in rats. Binding affinity and dose-related increase of TSH secretion were similar for both [Prot3] TRH and TRH. Moreover, similar effect of both peptides on sleeping time and motoric activity of rat was found. Substitution of L- for D-amino acids of TRH and [Prot3] TRH decreased the binding affinity and TSH-releasing activity as well. It was concluded that [Prot3] TRH analogue is as active as native TRH. PMID- 3106010 TI - Thyroid hormone-binding proteins in plasma facilitate uniform distribution of thyroxine within tissues: a perfused rat liver study. AB - We used autoradiography to test the hypothesis that a major function of thyroid hormone-binding proteins in plasma is to ensure uniform distribution of thyroid hormones among cells of a given tissue. The distribution of [125I]T4 within rat hepatic lobules was determined after its single pass perfusion through the portal vein in solutions containing or lacking thyroid hormone-binding proteins. These proteins included thyroid hormone-binding globulin, thyroid hormone-binding prealbumin, and albumin. In the absence of these proteins, virtually all of the perfused T4 was taken up by the periportal cells, and subsequent perfusion with protein-free solution did not cause redistribution of this T4. In the presence of these proteins, in contrast, the perfused T4 was taken up uniformly by all cells within the lobule. Albumin alone was sufficient to ensure uniform cellular uptake of T4. However, variation of oleic acid concentrations within the physiological range markedly influenced the concentration of free T4 in a solution of 4% human serum albumin, but not in human serum. These results indicate that uniform distribution of T4 within tissues requires circulating thyroid hormone-binding proteins, and that the specific binding proteins, thyroid hormone-binding globulin and thyroid hormone-binding prealbumin, are required to ensure nonfluctuating circulating concentrations of free T4 in vivo. Other hormone binding proteins in plasma and some transport proteins may function similarly. PMID- 3106011 TI - Dynamic actions of arachidonic acid and protein kinase C in pituitary stimulation by gonadotropin-releasing hormone. AB - The relative contributions of arachidonic acid (AA)- and protein kinase C dependent pathways during the immediate LH response to short term stimulation by GnRH were analyzed in perifused anterior pituitary cells cultured on Cytodex beads. The LH response to a 2-min pulse of 10 nM GnRH was biphasic, with a rapid increase to an initial peak, followed by a second peak or shoulder before the gradual return to baseline release. Retinal, which inhibits activation of protein kinase C, reduced the total LH response to GnRH by 35-40% and advanced the termination of the response, but did not alter the height, position, or rate of onset of the initial LH peak. In contrast, pretreatment with the lipoxygenase inhibitor nordihydroguaiaretic acid decreased the total LH response to GnRH by 60%, reduced the magnitude and latency of the first LH peak, and shortened the duration of the response. Pretreatment with both retinal and nordihydroguaiaretic acid abolished the GnRH-induced LH release. Addition of 2-min pulses of AA induced LH responses of short duration that coincided with the first phase of GnRH-stimulated LH release. Application of 2-min pulses of either tetradecanoyl phorbol 13-acetate (TPA) or dioctanoyl glycerol generated LH responses with delayed onsets that corresponded to the second phase of the GnRH-induced response. The LH response to the combined action of AA and TPA approximated that induced by GnRH. These results suggest that mobilization and metabolism of AA are important in the rapid initial phase of the LH response to GnRH, and that activation of protein kinase C-dependent mechanisms participates in the maintenance of the LH response. During continuous perifusion with 10 nM GnRH, addition of 2-min pulses of 100 nM GnRH and 100 microM AA, but not 100 nM TPA, stimulated further increases in LH release. This suggests that during prolonged GnRH action, LH release is primarily maintained by protein kinase C-dependent mechanisms. The results of this study indicate that GnRH stimulation of LH release requires the coordinated actions of at least two major interrelated mechanisms, namely those activated by AA and/or its metabolites and those maintained by protein kinase C-dependent pathways. PMID- 3106012 TI - Cholesterol side-chain cleavage P450 messenger ribonucleic acid: evidence for hormonal regulation in rat ovarian follicles and constitutive expression in corpora lutea. AB - Using an affinity-purified antibody against cholesterol side-chain cleavage P450 (P450scc) and a human P450scc cDNA probe, 11 rat P450scc cDNA clones were identified and isolated from our rat granulosa cell lambda gt11 cDNA expression library. Two clones were plaque purified and subcloned into pBR322. One of these P450scc cDNA clones, approximately 1.2 kilobases (kb) in size, was used as a probe for Northern and filter hybridization assays to analyze the tissue distribution and hormonal regulation of P450scc mRNA in rat ovarian follicles and corpora lutea. Northern transfers revealed a single P450scc mRNA species about 2.0 kb in size. Filter hybridization assays showed that P450scc mRNA was low in granulosa cells and thecal cells of small antral follicles, was increased in both tissues of preovulatory follicles, and was rapidly (within 7 h) and maximally increased (30-fold) during hCG-induced luteinization. P450scc enzyme and mRNA were also elevated in corpora lutea isolated from pregnant rats (days 4-22 of gestation) and rats 1 day after parturition (day 23). The elevation of P450scc enzyme and mRNA was maintained despite the marked decline in serum progesterone concentrations between days 19-22, suggesting that once P450scc mRNA is induced in luteal tissue it may be constitutively expressed. Administering hormones to granulosa cells in culture and to hypophysectomized immature rats in vivo demonstrated that the induction of P450scc mRNA by FSH in granulosa cells was time, dose, and estradiol dependent. High doses of FSH acting on estradiol-primed cells gave the greatest response. The increase in P450scc mRNA in cultured granulosa cells was also stimulated by forskolin and was directly associated with increased synthesis of cAMP and progesterone accumulation. Thus, whereas the induction of P450scc mRNA in granulosa cells was dependent on hormones and cAMP, the maintenance of P450scc mRNA and P450scc protein in corpora lutea appears to involve constitutive expression of P450scc mRNA. PMID- 3106013 TI - Tumor necrosis factor-alpha (cachectin) stimulates bone resorption in mouse calvaria via a prostaglandin-mediated mechanism. AB - Recombinant human (h) and murine (m) tumor necrosis factor (TNF)-alpha stimulated bone resorption and the production of prostaglandin (PG) E2 in neonatal mouse calvaria in organ culture. In experiments of 72-h duration, the effect on bone resorption was of large magnitude (an average increase in medium calcium of 3.3 mg/dl above control values in 11 separate experiments) and occurred over a concentration range of 0.1-20 ng/ml mTNF and 0.5-50 ng/ml hTNF. Accompanying the TNF-enhanced release of bone calcium there was enhanced accumulation of PGE2 in the culture medium. The increases in medium calcium and PGE2 were both inhibited completely by nontoxic concentrations of 4 different PG cyclooxygenase inhibitors (indomethacin, piroxicam, ibuprofen, and acetylsalicylic acid) but not by the noncyclooxygenase inhibitor salicylic acid. The magnitude of the PGE2 response, but not the calcium release, was less for bones treated with TNF than for those treated with equipotent doses of epidermal growth factor or human transforming growth factors-alpha or -beta, suggesting that the local site of production of PGE2 in bone may be different for TNF than for the other factors. Repeated sc injections of hTNF to intact mice for a 48-h period produced a statistically significant elevation of the plasma calcium concentration. Because TNF is produced by cells of the monocyte/macrophage lineage in response to invasive stimuli such as the presence of tumor, our findings indicate that a host factor produced in response to malignant cells can cause enhanced bone resorption. Thus, the concept of the humoral hypercalcemias of malignancy must be expanded to include mediators not produced by the tumor cells themselves. PMID- 3106014 TI - Potential precursors to neuromedin N in the cat and their processing by pepsin. AB - Acidic (0.1 N HCl) extracts of feline brain and ileal mucosa were found to contain a number of basic proteins which yielded immunoreactive neuromedin N (NMN) when treated with hog pepsin. These proteins substrates were separated using Sephadex G-25, Sephadex G-75, and reverse phase HPLC. In a calibrated sodium dodecyl sulfate-polyacrylamide gel electrophoresis system, the major substrates from cat ileum gave mol wt of about 15K and 20K. Minor bands of substrates, possible aggregates, were observed under both reducing and nonreducing conditions at 40K and 75K. Substrate-derived immunoreactive NMN was indistinguishable from synthetic or native NMN during reverse phase HPLC and gave equal measurements with two antisera with different specificities. During equilibrium centrifugation of isotonic homogenates of cat brain and ileum in a gradient of sucrose, NMN and the substrates banded together, apparently associated with particles resembling synaptosomes and vesicles. These results suggest that these substrates represent precursors to NMN and that pepsin can mimic the physiological processing enzyme(s) involved in the biosynthesis of this regulatory peptide. PMID- 3106015 TI - Estrogens, progestogens, and androgens enhance the follicle-stimulating hormone stimulated plasminogen activator production by cultured rat granulosa cells. AB - We have previously shown that FSH caused a dose-dependent increase in plasminogen activator (PA) production by cultured rat granulosa cells. PA production was assayed by culturing granulosa cells, obtained from immature diethylstilbestrol treated rats, on [125I]fibrin plates and determining the extent of fibrinolysis after the addition of the specific substrate plasminogen. To study the effect of ovarian steroids on FSH-stimulated PA production, concomitant treatment with FSH and estradiol [(E2) 10(-7) M], progesterone [(P) 10(-6) M], testosterone [(T) 10( 7) M] or 5 alpha-dihydrotestosterone [(DHT) 10(-7) M] were tested in these cultures. Treatment with E2 significantly enhanced the FSH-stimulated PA production by 35-210% over the whole range of the FSH dose response curve. The augmentation of FSH-stimulated PA production by E2 was not affected by the concomitant treatment with the antiprogestin RU 486 (10(-6) M). Similarly, P significantly enhanced the FSH-stimulated PA production by 34 to 90%. The stimulating action of P on FSH-dependent PA production was blocked by the simultaneous treatment with RU 486. Concomitant treatment with T significantly increased the FSH-induced PA production by 22-60%. That the effect of T was not due to the aromatization to E2 was evidenced by the augmentation by DHT of FSH stimulated PA production. DHT caused a significant 20-39% enhancement in the responsiveness of the granulosa cells to FSH by further increasing PA production. The enhancement of PA production by androgen is decreased partially by concomitant treatment with the antiandrogen flutamide (10(-5) M) and the antiprogestin RU 486. These in vitro data demonstrated the importance of estrogens, progestogens, and androgens in modulating the stimulating effect of FSH on PA production by immature rat granulosa cells. PMID- 3106017 TI - N-methyl-D,L-aspartate elicits hypothalamic gonadotropin-releasing hormone release in prepubertal male rhesus monkeys (Macaca mulatta). AB - In higher primates, the protracted delay from infancy to puberty results from an interruption in hypothalamic GnRH release. To determine whether the quiescent hypothalamic GnRH neurons of the prepubertal macaque are capable of discharging the decapeptide in response to a generalized neural depolarization, an excitatory amino acid analog, N-methyl-D,L-aspartate (NMA), was administered systemically to orchidectomized rhesus monkeys between 13 and 20 months of age. GnRH secretion was estimated indirectly by monitoring changes in circulating LH concentrations after the responsivity of pituitary gonadotropes to GnRH had been greatly facilitated by the chronic intermittent iv infusion of GnRH (0.1 microgram/min for 3 min every hour). The iv bolus administration of increasing doses of NMA (1.5, 4.8, and 15.0 mg/kg BW), 10-14 h after termination of the priming infusion of GnRH, elicited distinct discharges of LH, with magnitudes directly related to the amount of the excitant injected. Administration of a higher dose of NMA (48 mg/kg BW), however, failed to induce further LH release. The finding that pretreatment with a long-acting and potent GnRH receptor antagonist [( AcD2Nal1,4ClPhe2,DTrp3,DArg6,DAla10] GnRH-HOAc) abolished the LH-releasing activity of NMA provides compelling evidence for the view that the action of the neural excitant to induce gonadotropin release was exerted at a suprapituitary level. The additional observation that an N-methyl-D-aspartate receptor antagonist (D,L-2-amino-5-phosphono-valeric acid) blocked the NMA-induced release of GnRH suggests that the amino acid analog interacted with the N-methyl-D aspartate receptor on neurons that synthesize and/or control the release of the hypothalamic hormone. Most interestingly, three sequential GnRH discharges, with a period and an amplitude apparently similar to those generated by the hypothalamus of the adult, were elicited from the brain of prepubertal monkeys by the sequential administration of three injections of NMA at hourly intervals. Taken together these findings demonstrate that the apparent dormancy of hypothalamic GnRH neurons, which is characteristic of prepubertal development in higher primates and underlies the protracted delay in the onset of puberty in these species, may be readily terminated by application of a generalized neural excitation. Plasma FSH, PRL, GH, and cortisol concentrations were also monitored during the course of some of these experiments, and release of each of these four hormones was observed after the iv injection of NMA (15 mg/kg BW). PMID- 3106016 TI - Selective suppression of follicle-stimulating hormone by 3 alpha-hydroxy-4 pregnen-20-one, a steroid found in Sertoli cells. AB - Previous reports have not identified a naturally occurring steroid that selectively inhibits FSH secretion without also inhibiting LH secretion. The effect of 3 alpha-hydroxy-4-pregnen-20-one (3-HP), a steroid produced in Sertoli cells, on gonadotropin secretion in intact and castrate male and female, prepubertal and adult rats and in cultures of anterior pituitary cells was investigated. Intact prepubertal male rats were treated with a single sc injection of 0.2 mg/kg 3-HP, and castrate male and female rats were given a daily sc injection of 0.2 mg/kg 3-HP for 4 days. Serum FSH levels were suppressed by 26 44% (P less than 0.001-0.05), with no similar effect on serum LH levels. The acetyl derivative of 3-HP (3-HPA), administered to castrate prepubertal and adult rats for 4 days (0.625 mg/kg), resulted in significant decreases (P less than 0.001) in serum FSH to 45% and 19% of castrate control levels, respectively, without a significant effect on LH levels. Treatment of castrate prepubertal male rats with various doses of 3-HPA (0.001-0.625 mg/kg X day) for 4 days resulted in a dose-related suppression of serum FSH. Similar results were obtained with chronic (14-day) treatment of intact male rats with 3-HPA. Treatment of young (15 day-old) intact males with either 3-HP or 17 beta-hydroxy-5 alpha-androstan-3-one (DHT) for 14 days showed that DHT resulted in significant increases in prostate and seminal vesicle weights, while 3-HP showed no apparent androgenic activity. The effects of treatment with 3-HP, 3 beta-HP, 17 beta-estradiol, and DHT (0.025 0.625 mg/kg X day) were compared. Treatment with 3 beta-HP resulted in significant increases in serum FSH levels; 17 beta-estradiol and DHT suppressed both gonadotropins (at the higher doses administered), while 3-HP suppressed only FSH. 3-HP (3.16 X 10(-11) M) and/or LHRH (3 X 10(-8) M) were employed in primary cultures of anterior pituitary cells. Addition of LHRH resulted in 6- to 8-fold increases in the secretion of FSH and LH, while 3-HP suppressed basal (P less than 0.05) and LHRH-stimulated (P less than 0.001) FSH secretion by 26% and 77%, respectively. We conclude that 3-HP selectively suppresses FSH secretion and may be involved in the normal regulation of FSH secretion in the male. PMID- 3106018 TI - Prolactin inhibition by p-tyramine in the male rat: site of action. AB - In a previous report, a consistent hypoprolactinemic effect of p-tyramine was observed in male rats under several experimental conditions in vivo. In the present experiments the action of p-tyramine on PRL release in vitro, or after challenge with different hyperprolactinemic drugs (serotonin, morphine, and TRH) was tested. Furthermore the participation of octopamine, a metabolite of tyramine, was evaluated with regard to the hypoprolactinemic action of the amine. P-Tyramine inhibited PRL release from hemipituitaries incubated in vitro at doses of 10(-4) and 10(-6) M (inhibition to 31% and 59% of control values, respectively). When tested for its ability to displace [3H]spiperone binding in vitro to a crude fraction of anterior pituitary membranes it was found that it did not compete with the D2 receptor labeled by [3H]spiperone, even at the concentration of 10(-4) M. P-Tyramine (40 mg/kg) antagonized the elevation of serum PRL levels by morphine, serotonin, and TRH. On the other hand, octopamine, which is formed from tyramine, also inhibited high PRL values found after stress, though the effective dose was higher than that of tyramine. Pretreatment with diethyldithiocarbanic acid, which inhibits conversion of p-tyramine to octopamine, did not modify the effect of tyramine in stress. The present results indicate that tyramine can inhibit PRL release due to certain drugs, by acting directly at the pituitary level. It does not displace [3H]spiperone binding from anterior pituitary membranes, and octopamine which lowers PRL release itself, cannot account for the effect of tyramine. PMID- 3106019 TI - Epidermal growth factor enhances [125I]iodo-follicle-stimulating hormone binding by cultured porcine granulosa cells. AB - Epidermal growth factor (EGF) has been shown to have diverse effects on granulosa cells (GC). Although a potent mitogen for GC from several species, EGF attenuates many FSH-mediated processes associated with GC differentiation, suggesting that EGF promotes cell proliferation at the expense of cell differentiation. The extent to which EGF effects involve modulation of the FSH receptor level in proliferating GC has not been established. Accordingly, we investigated the effect of EGF on [125I]iodo-FSH binding by porcine GC isolated from small follicles maintained in monolayer cultures. Relative to cells cultured in medium with insulin alone, EGF treatment increased total monolayer [125I]iodo-FSH binding (per culture) 120% (P less than 0.005). This was due to a 40-50% (P less than 0.01) increase in binding per U protein and/or per U cell and a 40-60% (P less than 0.005) increase in both monolayer cell and protein contents. EGF stimulated GC hyperplasia, but not hypertrophy. Optimum EGF doses for increased total monolayer [125I]iodo-FSH binding and binding normalized per U protein or cell were 0.5 and 0.1 ng/ml, respectively. Fibroblast growth factor was 20- to 100-fold less potent than EGF, and thrombin was without effect. Whereas [125I]iodo-FSH binding per U protein or cell was not affected by the serum concentration of the culture medium, the EGF effects on total monolayer binding and cell proliferation were directly related to the serum concentration (P less than 0.005). Thus, EGF-mediated increases in total monolayer [125I]iodo-FSH binding were paralleled by increases in cell number. The equilibrium dissociation constants (Kd) for [125I]iodo-FSH binding to cells cultured with and without EGF were 5.3 and 2.5 X 10(-10) M, respectively. Thus, EGF treatment significantly increased FSH receptor number, but significantly decreased receptor-binding affinity (P less than 0.05). Chronic FSH treatment during monolayer culture decreased total monolayer [125I]iodo-FSH binding and binding per U protein or per cell and attenuated EGF-stimulated cell proliferation, but markedly stimulated cell hypertrophy. Thus, concomitant treatment with EGF and FSH stimulated cell hypertrophy rather than hyperplasia. EGF and FSH each would appear capable of modulating the action of the other with respect to GC function. Our results indicate that EGF-mediated GC proliferation is associated with the expression of FSH-binding sites. This appears to be due to both an increase in FSH receptors among the cell population and an increase in the monolayer cell population.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3106020 TI - Effects of interferon-gamma and other cytokines on collagen synthesis in fetal rat bone cultures. AB - Control of trabecular bone volume is mediated by local events. Recently, it has been shown that the cytokines interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha), and TNF beta [also called lymphotoxin (LT)] produced by immune cells all stimulate osteoclast activity, whereas the lymphokine interferon-gamma (IFN gamma) inhibits osteoclast activity stimulated by these agents. We report here the effects of each of these cytokines on bone collagen content measured as incorporation of proline into collagen and noncollagen protein in 20-day-old fetal rat calvariae. We found that IL-1, LT, and TNF decreased bone collagen synthesis and, to a lesser degree, noncollagen protein synthesis when the bones were exposed continuously to these agents. In addition, these cytokines stimulated DNA synthesis in the calvariae. In contrast to its action on bone resorption, where it opposed the resorptive effects of IL-1, TNF, and LT, IFN gamma inhibited bone collagen synthesis and had an additive effect with TNF and LT when bones were exposed to both. However, unlike the other cytokines, IFN gamma also decreased DNA synthesis in the calvariae. These data indicate that cytokines released by immune cells in the bone marrow microenvironment may work in concert to affect osteoblast activity in vitro. PMID- 3106022 TI - Characterization of the content of occluded biliary endoprostheses. AB - In an attempt to establish why biliary endoprostheses clog we analysed the contents of 21 occluded endoprostheses. The major components of the endoprosthesis sludge were protein (25%) and an insoluble residue (20%) which consisted mainly of plant fibers. Compared with bile the material was also rich in unconjugated bilirubin, while the major components of bile--bile acids and lecithin--accounted for only 15%. Although the sludge often contained some cholesterol crystals, no cholesterol gallstones or pigment or mixed stones were found. The material contained bacteria, but not in abundance. Scanning electron microscopy of the walls of clogged endoprostheses revealed adherence of amorphous material, probably protein. SDS-polyacrylamide gel electrophoresis of the protein fraction of the material from different endoprostheses showed a characteristic pattern. The material always contained two major bands of approximately 16 and 13 kDalton, which were not observed in corresponding bile samples. The 16 and 13 kDalton proteins bound most avidly to the endoprosthesis wall. We postulate that the initial phase in the clogging process is adsorption of proteins, after which other materials such as bacteria, fibers from food and unconjugated bilirubin bind to the wall of the endoprosthesis. PMID- 3106021 TI - Lipoxygenase inhibitors reduce insulin secretion without impairing calcium mobilization. AB - Inhibitors of pancreatic islet lipoxygenase (LPX) impair nutrient-induced insulin (I) release. To define the mechanism of action of these inhibitors, studies were carried out at subthreshold glucose concentrations (0-1.7 mM) in order to minimize any effects of LPX blockade on the potentiating effect of extracellular fuels. Barium chloride (Ba2+; 2 mM) increased 45Ca2+ release from prelabeled islets in Ca2+-free medium and, thus, is a model for the mobilization of intracellular Ca2+ stores. Inhibition of LPX (using nordihydroguaiaretic acid, BW755c [3-amino-1-(trifluomethyl-phenyl)2-pyrazoline] or butylated hydroxytoluene) did not have any consistent effect on the influx of Ba2+ (as assessed by 133Ba uptake) or on the consequent release of cellular Ca2+ stores; however, each LPX inhibitor vitiated Ba2+-induced I release. The LPX inhibitors were not merely acting as nonspecific antioxidants, since two inhibitors which do not act by scavenging hydroperoxides (5,8,11,14-eicosatetraynoic acid and 15 hydroxy-5,8,11,13-eicosatetraenoic acid) also impeded the effect of Ba2+ on I secretion; furthermore, a series of hydroxyl radical scavengers, reducing agents, or agents that block nonenzymatic and/or NADPH-activated lipid peroxidation did not inhibit I secretion. LPX inhibitors also blocked the residual I response to 16.7 mM glucose in Ca2+-free medium. Additionally, they reduced secretion induced by 46 mM K+ or 1 mM isobutylmethylxanthine (provided in the presence of extracellular Ca2+), without inhibiting K+- or isobutylmethylxanthine-induced Ca2+ fluxes. Stimuli sensitive to LPX blockade were also antagonized by antimycin A (an inhibitor of energy flux) or TMB-8 [8-(N,N-diethylamino)octyl 3,4,5 trimethoxybenzoate hydrochloride; which appeared to deplete critical intracellular Ca2+ stores]. In contrast, the effects of exogenous phospholipase C (and several other Ca2+-dependent membrane-active agonists) were resistant to the LPX inhibitors, TMB-8, and antimycin A; thus, LPX inhibitors are not nonspecific global poisons of all Ca2+-dependent exocytotic hormone release. We conclude that LPX (or a very similar enzyme) may modulate the effects (or redistribution) of an ATP-dependent trigger pool of Ca2+ at a site distal to and independent of its mobilization by primary islet agonists. LPX inhibitors also blocked secretion induced by 12-O-tetradecanoyl-phorbol-13-acetate; this effect may reflect an effect of LPX on the activation of protein kinase C or a modulation of its synergism with the same trigger Ca2+ pool(s). PMID- 3106023 TI - Fluorescence correlation spectroscopy in the nanosecond time range: rotational diffusion of bovine carbonic anhydrase B. AB - A fluorescence correlation experiment for measurement of rotational diffusion in the nanosecond time scale is described. Using this method, the rotational diffusion coefficient of bovine carbonic anhydrase B labelled with tetramethylrhodamine isothiocyanate was estimated to be Dr = (1.14 +/- 0.15) X 10(7) s-1 at 22 degrees C. The experiment is based on a cw argon ion laser, a microfluorometer with local solution flow inside the sample cell, and two photon detectors. The fluorescence intensity autocorrelation function in the nanosecond time range is computed with the help of a time-to-amplitude converter and a multichannel pulse-amplitude analyser. PMID- 3106024 TI - Evaluation of Pluronic Polyol F127 as a vehicle for petroleum hydrocarbons in the Salmonella/microsomal assay. AB - Complex hydrocarbon mixtures have proven difficult to evaluate in in vitro mutagenicity assays owing to their insolubility in aqueous environments. Pluronic Polyol F127 (BASF Wyandotte, Parsippany, NJ), prepared as a 50% (w/w) solution in absolute ethanol, proved effective in emulsifying various petroleum hydrocarbon fractions. Its effectiveness in the Salmonella/microsomal assay was evaluated using model solutions each comprising a polycyclic aromatic hydrocarbon (PAH) dissolved in mineral oil. The PAHs used were benzo(a)pyrene, 3 methylcholanthrene, and 7,12-dimethylbenz(a)anthracene. Model solutions were evaluated neat and as emulsions with the Pluronic F127 solution or Tween 80. Similar levels of each PAH were prepared in dimethyl sulfoxide (DMSO) for comparison. Cytotoxicity and mutagenesis were evaluated in the preincubation technique using strain TA97. Little or no cytotoxicity or mutagenesis was evident for model solutions tested neat. However, emulsification of these PAH-laden mixtures with the Pluronic F127 solution yielded cytotoxic and mutagenic responses similar to, or greater than, those observed for PAHs delivered in DMSO. Model mixtures emulsified with Tween 80 were less active. Study results demonstrate that Pluronic F127, prepared as a 50% (w/w) solution in absolute ethanol, is an effective vehicle for evaluating the mutagenic potential of complex hydrocarbon mixtures containing PAHs in the Salmonella/microsomal assay. Since PAHs are a class of insoluble hydrocarbons, the results also suggest the potential usefulness of the Pluronic F127 solution to detect the mutagenicity of other insoluble hydrocarbons and hydrocarbon mixtures. PMID- 3106025 TI - Lack of mutagenicity of the organophosphorus insecticide malathion in Drosophila melanogaster. PMID- 3106026 TI - Generation of hemolytic activity in ozone-treated phosphatidylcholine. AB - When liposomes prepared from purified soybean phosphatidylcholine were treated with ozone, at least two types of hemolytic agents were formed. One type was stable at 0 degree C but was destroyed rapidly at 37 degrees C. A second type was evolved during storage of ozone-treated phosphatidylcholine at 37 degrees C in the absence of EDTA. This study is concerned mainly with the heat-labile type. The hemolytic activity was not associated with lipid hydroperoxides. A number of substances were shown to inhibit the hemolytic activity and these may be divided into two classes. The first included cysteine, polyamines, n-heptylamine, semicarbazide, and tryptophan. Preincubation of the ozone-treated phosphatidylcholine was necessary with a Class 1 inhibitor, presumably for the interaction of the inhibitor with a functional group of the hemolytic agents. The Class II inhibitors, including BHT and vitamin C, required no preincubation. These possibly abolished the hemolytic activity by scavenging free radicals in the process. PMID- 3106027 TI - The effects of "yusho" type PCB on triglyceride lipase and fatty acid composition. AB - Yusho type polychlorinated biphenyl (Y-PCB) was prepared in order to study lipid disorder of the PCB poisoning "yusho." Y-PCB caused hypertriglyceridemia and hypercholesterolemia in the rat. Triglyceride lipase (TGL) activities in liver and postheparin serum were suppressed by Y-PCB administration, whereas it was not suppressed in fat. In in vitro experiments, Y-PCB did not suppress TGL in either liver or fat. Although Y-PCB increased fatty acids in the liver 2.5-fold, the relative proportion of fatty acids composition was not changed so remarkably as that in absolute concentrations. These findings suggested that liver is the target of Y-PCB -mediated alteration of lipid metabolism. PMID- 3106028 TI - Childhood lead toxicity and impaired release of thyrotropin-stimulating hormone. AB - Decreased stature of children is epidemiologically associated with increased blood lead independent of multiple socioeconomic and nutritional variables. Since endocrine dysfunction occurs in adult lead workers, we studied two girls, 2 years of age, before and after calcium disodium edetate chelation for blood leads (PbB) of 19-72 micrograms/dl. The height of both children had crossed from the 50th to below the 10th percentile during the course of chronic lead toxicity. Basal free T4, T4, T3, cortisol, somatomedin C, and sex steroids were normal. A decrease in the growth hormone response and elevation of basal prolactin and gonadotropins were noted in one. Both children demonstrated blunted thyrotropin-stimulating hormone (TSH) responses to thyrotropin-releasing hormone (TRH) in six of seven challenges. This prompted in vitro studies of cultured cells from rat pituitaries. After incubation of pituitary cells with 0.1-10 microM Pb2+ for 2 hr, followed by the addition of TRH, there was a dose-dependent inhibition of TSH release. Lead did not interfere with the assay of TSH. To investigate the interaction of lead and calcium, 45Ca2+ kinetic analyses were done on rat pituitary slices after 1 hr incubation with 1.0 microM lead. The impaired late efflux was consistent with a decrease in the size and exchangeability of the tightly bound pool of intracellular microsomal or mitochondrial calcium. The rat pituitary cell model provides a model for the decreased TSH release of lead poisoning, supports the biological plausibility of a neuroendocrine effect on growth, and suggests that interference with calcium-mediated intracellular responses is a basic mechanism of lead toxicity. PMID- 3106029 TI - Identity of rat liver mitochondrial asparagine-pyruvate transaminase with phenylalanine-pyruvate transaminase. AB - Identification of rat liver mitochondrial asparagine-pyruvate transaminase with phenylalanine-pyruvate transaminase has been done. When a mitochondria extract was subjected to isoelectric focusing, the two enzyme activities were identically focused. This procedure and DEAE-Sepharose chromatography revealed multiple forms of the enzyme, in which the main form was purified. In the various purification steps the two enzyme activities appeared in the same fraction. The enzyme of the final preparation step gave a single band in polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. During the purification, a similar increase of the specific activity and yield were obtained in the two activities. Phenylalanine was found to be a competitive inhibitor of asparagine transaminase. These results suggest the identity of the two enzymes. PMID- 3106030 TI - Polymorphism of aldehyde dehydrogenase and alcohol sensitivity. AB - The metabolism of acetaldehyde has received considerable attention in the past years owing to its acute and chronic toxic effects in humans. Aldehyde dehydrogenase (ALDH) catalyzes the oxidation of acetaldehyde in liver and other organs. Two major isozymes of hepatic ALDH (ALDH I or E2 and ALDH II or E1), which differ in their structural and functional properties, have been characterized in humans. The ALDH I with a low Km for acetaldehyde is predominantly of mitochondrial origin and ALDH II which has a relatively higher Km is of cytosolic origin. An inherited deficiency of ALDH I isozyme has been found among Japanese and Chinese which is primarily responsible for producing acute alcohol sensitivity symptoms (flushing response) after drinking mild doses of alcohol. Biochemical, immunochemical and molecular genetics data indicate a structural mutation in the ALDH I isozyme gene responsible for the loss in catalytic activity. Population genetic studies indicate a wide prevalence of this ALDH polymorphism among individuals of Mongoloid race. Flushing response to alcohol shows familial resemblances and preliminary family data from Japan, China and Korea hint to an autosomal codominant inheritance for ALDH I isozyme deficiency. The ALDH polymorphism is apparently responsible for the low incidence of alcoholism in Japanese, Chinese and Koreans. Alcohol-induced sensitivity due to ALDH isozyme deficiency may act as an inhibitory factor against excessive alcohol drinking thereby imparting a protection against alcoholism. PMID- 3106031 TI - Microsomal ethanol-oxidizing system. AB - Advances in our knowledge of the microsomal metabolism of ethanol enable us to understand a number of complications that develop in the alcoholic. After chronic ethanol consumption, microsomal ethanol-oxidizing system (MEOS) activity increases with an associated rise in microsomal cytochrome P-450, including a form different from that induced by phenobarbital and methylcholanthrene and which has a high affinity for ethanol, as shown in reconstituted systems. The role of this MEOS in vivo and its increase after chronic ethanol consumption was most conclusively shown in alcohol dehydrogenase-negative deer mice. Microsomal induction is also associated with enhanced metabolism of other drugs, resulting in metabolic drug tolerance. Furthermore, there is increased conversion to toxic metabolites of known hepatotoxic agents (such as CCl4), which may explain the enhanced susceptibility of alcoholics to the toxicity of industrial solvents. Furthermore, the ethanol-induced form of cytochrome P-450 has a high capacity for the conversion to toxic metabolites of some commonly used drugs, such as acetaminophen, and also carcinogens, such as dimethylnitrosamine which is activated at concentrations much lower than those required for other microsomal inducers. Moreover, catabolism of retinol is accelerated through a newly discovered microsomal pathway, thereby contributing to hepatic vitamin A depletion and possibly vitamin A toxicity. There is also induction of microsomal enzymes involved in lipoprotein production, resulting in hyperlipemia. Contrasting with the chronic effects of ethanol consumption, acutely, ethanol inhibits the metabolism of other drugs through competition for an at least partially shared microsomal detoxification pathway. PMID- 3106032 TI - Ventilatory control studied with circulatory occlusion during exercise recovery. AB - Mechanisms involved in the control of pulmonary ventilation were studied in seven male subjects following 6 min of exercise on a cycle ergometer at 98w. Circulation to the legs was occluded by thigh cuffs (27 kPa) during the last 15 s of exercise and the subsequent 4 min of recovery. Respiratory gas exchange and the tidal partial pressures of O2 and CO2 were measured breath-by-breath. The results were compared to control studies without occlusion. There was a significant increase in both systolic and diastolic blood pressures during occluded recovery. Following occlusion systolic pressure remained elevated while diastolic pressure returned to control values. Occlusion during recovery caused hyperventilation during the first 1.5 min after exercise as evidenced by significantly higher VE/VCO2, VE/VO2, PETO2, and lower PETCO2. Following the release of the cuffs PETCO2, VE, VCO2, VO2, and heart rate all increased significantly above control values, while PETO2 decreased. PETCO2 rose abruptly 14.5 +/- 0.9 s after the release of the cuffs. Marked increases in VE and heart rate were seen, and occurred 30.8 +/- 1.5 s and 12.8 +/- 1.3 s, respectively, after cuff release. The 16.3 +/- 1.4 s lag between the increase in PETCO2 and VE after occlusion suggests that the ventilatory response to a sudden load of hypercapnic blood is not mediated by a pulmonary chemoreceptor. Other receptors, probably the peripheral chemoreceptors, appear to be responsible for hypercapnic hyperventilation. PMID- 3106033 TI - Resistant strains of Pseudomonas aeruginosa isolated after exposure to several beta-lactam antibiotics. AB - Successive transfer of three clinical isolates of Pseudomonas aeruginosa in liquid medium containing serial dilutions of several beta-lactam antibiotics was used to isolate resistant variants. The alpha-carboxy-penicillins (carbenicillin and ticarcillin), the acylureidopenicillins (piperacillin and azlocillin) and cephalosporins (moxalactam, cefoperazone, cefsulodin and ceftazidime) were used as the selective antibiotics. Resistant variants were isolated from two of the three strains (strains 27 and 45), using an inoculum size of 10(4)-10(5) CFU/ml, which showed a mean 5 to 8-fold increase in MIC for most of the selected antibiotics. The 27-carbenicillin and 27-cefsulodin resistant variants showed beta-lactamase production similar to that of the parent. However, alterations were found in outer-membrane proteins and lipopolysaccharides. With azlocillin, moxalactam and ceftazidime as the selective antibiotics, resistant variants were isolated from strains 27 and 45 which showed a stable increased constitutive beta lactamase production. From the third strain, 9150, the only variants isolated showed a two dilution-step increase in MIC to the antibiotics tested. The beta lactamase production, outer-membrane proteins and lipopolysaccharides of these variants were similar to those of the parent. PMID- 3106034 TI - Serum bactericidal activity of ciprofloxacin and ofloxacin in volunteers. AB - The serum bactericidal activity of two newer quinolones, ciprofloxacin and ofloxacin, against 206 clinical bacterial isolates was determined in six male volunteers after oral administration of either 500 mg of ciprofloxacin or 200 mg of ofloxacin respectively. The highest bactericidal titers were achieved against Enterobacteriaceae 1 h after ciprofloxacin administration, ranging from 1:121 for indole-positive Proteus species to 1:30 for Serratia spp. Ofloxacin generated lower titers, ranging from 1:14 for indole-positive Proteus spp. to 1:2.5 for Enterobacter spp. Only low serum bactericidal titers were found for Pseudomonas aeruginosa, Acinetobacter spp. and gram-positive cocci. It is concluded that the activity of orally administered ciprofloxacin is superior to that of orally administered ofloxacin in the serum bactericidal test. PMID- 3106035 TI - Nucleotide sequence of a cellulase gene of Bacillus subtilis. AB - The nucleotide sequence of an endolytic cellulase gene of Bacillus subtilis was determined and compared with the NH2-terminal amino acid sequence of the purified enzyme. The mature protein appeared to be extended by a signal sequence of 36 amino acids. The putative AUG initiation codon was preceded by a sigma 43-type promoter of B. subtilis and an AAGGAGG sequence, typical of procaryotic ribosomal binding sites. Partial homology of amino acid sequences was found between B. subtilis cellulase and an alkalophilic Bacillus cellulase. PMID- 3106036 TI - Free apolipoproteins A-I and A-IV present in human plasma displace high-density lipoprotein on cultured bovine aortic endothelial cells. AB - Adult bovine aortic endothelial (ABAE) cells, exposed to serum-free medium, specifically bind 125I-labeled human high-density lipoprotein (125I-HDL). Addition of human lipoprotein-deficient serum (LPDS) reduces the specific binding of 125I-HDL in a concentration-dependent manner, such that LPDS at a concentration of 6 mg protein/ml almost completely inhibits the specific binding of 125I-HDL. ABAE cultures exposed to 125I-labeled LPDS (125I-LPDS) specifically bind two peptides, which appear as minor iodinated components in 125I-LPDS. The binding of these two components is abolished in the presence of excess amounts of unlabeled LPDS or HDL. Preincubation of ABAE cells with 25-hydroxycholesterol (25 HC) results in an increase in the binding of the two 125I-LPDS components, similar to the increase observed in 125I-HDL binding in the presence of 25-HC. These two LPDS components comigrate on sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) with apolipoproteins A-I and A-IV of molecular masses 28 kDa and 43 kDa respectively. Furthermore, these two proteins were transferred from the SDS gel to nitrocellulose paper and interacted specifically with anti-(A I) and anti-(A-IV) sera respectively. When ABAE cultures, pretreated with 25-HC in the presence of LPDS, are subjected to cell-surface iodination, the A-IV appears as one of the major proteins on the cell surface accessible to iodination. The interaction of A-IV with the cell surface of 25-HC-treated cells is not specific to ABAE cells and appears also in human skin fibroblasts. Analysis of the relative amounts of various apolipoproteins in the 125I-HDL bound to ABAE cells demonstrates a decrease in the relative amount of iodinated A-II concomitant with increase in the relative amounts of the other iodinated apolipoproteins, when compared to the composition of the native 125I-HDL. These changes are similar whether the binding is done in the presence or absence of LPDS. It indicates that the decrease in 125I-HDL binding in the presence of LPDS is not due to displacement of the iodinated apolipoproteins A-I and A-IV in the 125I-HDL by unlabeled A-I and A-IV present in LPDS. The results indicate that free apolipoproteins A-I and A-IV, present in LPDS, can displace HDL on the cell surface of ABAE cells. Thus, free A-I and A-IV, present in plasma, control the binding of HDL to endothelial cells and may regulate the process of cholesterol removal from the cells performed by HDL. PMID- 3106037 TI - Purification and characterization of extracellular alpha-amylase and glucoamylase from the yeast Candida antarctica CBS 6678. AB - An alpha-amylase and a glucoamylase were purified to homogeneity from the culture fluid of beta-cyclodextrin-grown Candida antarctica CBS 6678 by protamine sulfate treatment, ammonium sulfate precipitation, gel filtration (Sephadex G-75 sf, Ultrogel AcA 54), DEAE-Sephacel chromatography, hydroxyapatite chromatography and affinity chromatography on acarbose--AH-Sepharose 4B. Both enzymes were monomeric glycoproteins with fairly different amino acid compositions. Their apparent relative molecular mass, sedimentation coefficient (Szero20,w), isoelectric point, absorption coefficient (280 nm), pH and temperature optima were estimated as 48,500, 4.7 S, 10.1, 1.74 cm2 mg-1, 4.2 and 57 degrees C, respectively, for glucoamylase and as 50,000, 4.9 S, 10.3, 1.53 cm2 mg-1, 4.2 and 62 degrees C, respectively, for alpha-amylase. Kinetic analyses indicated that both enzymes preferentially hydrolyzed high-molecular-mass substrates, including some raw starches. alpha-Amylase was active on cyclodextrins, whereas debranching activity was demonstrated for glucoamylase. Trestatins were potent inhibitors of both alpha-amylase (Ki less than 1 microM) and glucoamylase (Ki less than 0.1 microM), being more effective than Bay e 4609 (Ki less than 10 microM). Glucoamylase was selectivity and strongly inhibited by acarbose (Ki less than 0.1 microM). Activity of the latter enzyme was also affected by 1-deoxynojirimycin (Ki less than 1 mM), maltitol and amino alcohols (Ki less than 10 mM). Unlike alpha amylase, glucoamylase adsorbed strongly onto raw starch, the adsorption site being non-identical with the active site. PMID- 3106038 TI - The titre of juvenile hormone during the pupal and adult stages of the life cycle of Drosophila melanogaster. AB - Using combined gas chromatography/selected-ion mass spectroscopy, the titer of juvenile hormone was determined for whole-body extracts at various morphologically defined stages of the life cycle of Drosophila melanogaster. Only juvenile hormone III (JH-III) was detected. JH-III is present in early metamorphosis but by mid-metamorphosis it is below the level of detection (0.05 pmol/g). It then increases as the pharate adult matures and rises dramatically, beginning just prior to eclosion and reaching 5-7 pmol/g shortly after eclosion. The titer then begins to fall again as the adults mature in both males and females, though the decrease is more rapid in females. Preliminary studies show that low levels of JH-III are present during all the larval instars but are absent from eggs. PMID- 3106039 TI - Mode of inhibition of the DNA polymerase of Methanococcus vannielii by aphidicolin. AB - The mode of action of aphidicolin on DNA synthesis catalysed by the DNA polymerase of Methanococcus vannielii is competitive for dCTP, noncompetitive for dATP, dGTP and dTTP and uncompetitive for activated DNA. The kinetic data are accounted for by a mechanism in which dCTP and aphidicolin compete for the dCTP specific binding site on the DNA polymerase. The dissociation constant for the aphidicolin--DNA-polymerase complex is 0.04-0.07 microM. Similar modes of inhibition of DNA synthesis exist for DNA polymerase alpha of higher eucaryotes but not for eubacteria or viruses and suggests a close functional relationship between the DNA polymerase of eucaryotes and of the archaebacterium M. vannielii. PMID- 3106040 TI - Purification and immunochemical characterization of the major pertussis-toxin sensitive guanine-nucleotide-binding protein of bovine-neutrophil membranes. AB - Bovine peripheral neutrophils contain high levels of a 40-kDa pertussis toxin substrate, which was found highly enriched in a light membrane fraction upon subcellular fractionation of neutrophil homogenates. The 40-kDa pertussis toxin substrate, referred to as alpha n, was purified to near homogeneity from this fraction by sequential ion-exchange, gel-filtration and hydrophobic chromatography. Purified alpha n was shown to interact with beta gamma subunits, undergo ADP-ribosylation by pertussis toxin, and bind guanine nucleotides with high affinity. The mobility of purified alpha n on SDS/polyacrylamide gels was intermediate between those of the alpha subunits of Gi and Go, purified from bovine brain, and slightly lower than the mobility of the alpha subunit of transducin (Gt). Several polyclonal antisera against the alpha subunits of bovine Gt and Go did not react with alpha n on immunoblots. CW 6, a polyclonal antiserum reactive against the bovine alpha i, reacted only minimally with alpha n. These results suggest that the major pertussis toxin substrate of bovine neutrophils, designated Gn, is structurally different from previously identified pertussis toxin substrates and may represent a novel guanine-nucleotide-binding protein. PMID- 3106042 TI - Nucleotide sequence of barley chymotrypsin inhibitor-2 (CI-2) and its expression in normal and high-lysine barley. AB - cDNA clones for chymotrypsin inhibitor-2 (CI-2) have been isolated from an endosperm-specific library of barley using a synthetic oligonucleotide probe. The nucleotide sequences of several of the cDNAs predict an open reading frame (beginning with an ATG codon) which encodes a protein of 84 residues (Mr 9380). In the longest clone another ATG codon is present, a further 69 nucleotides upstream. The nucleotide sequence between these two ATG codons predicts an amino acid sequence with the characteristics of a signal peptide, as found in other cloned plant protease inhibitors. However, it contains an in-frame TAA stop codon, which is also present in all of the shorter cDNAs which extend into this region. From in vitro translation experiments, using mRNAs synthesized from cDNAs, we conclude that, in vitro, translation of all or the vast majority of CI 2 mRNAs begins at the second ATG codon, 31 nucleotides downstream from the ochre stop codon. Southern blotting of genomic DNA shows that CI-2 is encoded by a small multigene family, while sequence analysis of the cDNAs shows that at least two sub-families of mRNAs, which are more than 90% homologous, are present in the endosperm. Northern blotting analysis shows that related but different sequences are present in leaf and shoot RNA populations. Further Northern blot hybridizations using RNA from the normal line, Sundance, and the high-lysine barley mutant, Hiproly, show that endosperms of the latter contain greatly increased levels of CI-2 mRNA. This correlates with the increased amount of CI-2 protein deposited in Hiproly, and demonstrates that the differential expression of CI-2 in the two genotypes is controlled at the level of transcription and/or stability of the mRNA. In contrast, the abundance of CI-2 mRNAs in leaves and shoots is not affected. PMID- 3106041 TI - Glucose-6-phosphate oxidation pathway in rat-liver microsomal vesicles. Stimulation under oxidative stress. AB - The glucose-6-phosphate oxidation pathway present in microsomes was studied using intact microsomal membranes. The oxidation activity, which was measured by monitoring the formation of 14CO2 from [1-14C]glucose 6-phosphate, was greatly stimulated when azodicarboxylic acid bis(dimethylamide), methylene blue or cumene hydroperoxide was added to the assay mixture. Glutathione peroxidase and glutathione reductase are suggested to be involved in the oxidation reaction induced by these oxidizing reagents. We detected a significant activity of the glutathione reductase inherent to microsomes. The microsomal glutathione reductase is latent and requires detergent to reveal its activity. 4,4' Diisothiocyanostilbene 2,2'-disulfonic acid (DIDS) inhibited the 14CO2 formation, but the inhibition was released by the addition of a detergent. Moreover, the inhibitory effect of DIDS was reversed by glucose 6-phosphate but not by mannose 6-phosphate. We conclude that the glucose-6-phosphate oxidation pathway in intact microsomes starts working under oxidative stress and that a transporter specific for glucose 6-phosphate is involved in the reaction. PMID- 3106044 TI - Cost-effectiveness analysis of single-dose therapy of urinary tract infection compared to conventional treatment. AB - A cost effectiveness analysis comparing single-dose with conventional antibiotic treatment for uncomplicated urinary tract infection is described. The analysis is based on aggregated effectiveness and side effect rates reported in the medical literature. A comparison of single-dose and conventional regimens of trimethoprim sulfamethoxazole and amoxicillin indicates that single-dose regimens are preferable to conventional regimens of either drug, and that trimethoprim sulfamethoxazole is preferable to amoxicillin, on the grounds both of days of morbidity averted and of medical care costs. Thus single-dose therapy is cost effective compared to conventional treatment. PMID- 3106043 TI - Improved tumor localization of 111In labeled monoclonal antibody with chelator administration to host nude mice. AB - Administration of calcium disodium edetate (EDTA) substantially increased the tumor:muscle ratios of nude mice injected with 111In labeled monoclonal antibody 9.2.27. This effect was apparent 3 days to 7 days after antibody injection of mice bearing the BRO human melanoma, but not earlier. The tumor:muscle ratios decreased during this time for animals not receiving chelator. Contemporaneously, EDTA treated mice lost whole body radioactivity more rapidly than did their untreated counterparts, suggesting that 111In which had dissociated from the antibody-DTPA-radiometal complex was chelated and excreted. These results suggest that effective chelator treatment might improve tumor localization of radioactivity after injection of 111In labeled antibodies. PMID- 3106045 TI - Monuril and modification of pathogenicity traits in resistant microorganisms. PMID- 3106046 TI - Insulin sensitivity and beta-cell function assessed by C-peptide in young adults with cystic fibrosis. AB - Eight patients with cystic fibrosis (CF) aged 18-34 who had normal random plasma glucose levels were studied with a continuous infusion of glucose with model assessment (CIGMA) and plasma C-peptide to assess beta-cell function, and plasma insulin to assess insulin sensitivity. Two had impaired glucose tolerance, two had impaired beta-cell function and all had normal insulin sensitivity. The results of previous studies suggesting that glucose intolerance is common in CF may reflect the inability of an impaired liver to handle a large oral glucose load. The few CF patients who become diabetic may be those who have a preexisting diabetic trait. PMID- 3106047 TI - Very low density lipoprotein metabolism after insulin over-treatment and during a euglycaemic clamp. AB - The disturbance of very low density lipoprotein (VLDL) metabolism that occurs as a result of intensive insulin treatment and during a euglycaemic clamp have been investigated in a rat model. Normal rats were maintained with fed blood glucose levels below 5 mmol l-1 for 8 weeks by subcutaneous insulin injections (normal fed levels 5.8 +/- 0.4 (SD) mmol l-1). Glucose requirement to maintain a glucose clamp was significantly reduced (116 +/- 3 mumol min-1 kg-1 (SE) vs. 173 +/- 5 mumol min-1 kg-1, P less than 0.001), compared with weight-matched normal control rats. In the fasting state (blood glucose 3.5 +/- 0.2 mmol l-1 vs. 3.9 +/- 0.1 mmol l-1, NS) plasma non-esterified fatty acid levels were reduced. Fasting VLDL triglyceride turnover, measured by bolus injection of 14C-VLDL, was also lower (3.17 +/- 0.12 mumol min-1 kg-1 vs. 3.50 +/- 0.07 mumol min-1 kg-1, P less than 0.05). Despite decreased turnover, insulin over-treated rats had normal plasma triglyceride concentrations indicating a removal defect. At the end of a 3-h euglycaemic clamp, plasma triglyceride concentrations and VLDL-triglyceride turnover were decreased in both normal control and insulin over-treated animals, and turnover remained significantly lower in the insulin over-treated rats (2.59 +/- 0.13 mumol min-1 kg-1 vs. 3.08 +/- 0.10 mumol min-1 kg-1, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106048 TI - Acetaldehyde modification of low density lipoprotein accelerates its catabolism in man. AB - Acetaldehyde (AcA), the first metabolite in ethanol oxidation, is chemically highly reactive and binds covalently to the free amino groups of various proteins. In this study, we examined the metabolism of acetaldehyde-modified LDL (AcA-LDL) in man. LDL was isolated from human volunteers, radiolabelled with either 125I or 131I, incubated in various AcA concentrations (Aca-LDL) and injected back into the donors simultaneously with LDL incubated in identical conditions but omitting AcA (C-LDL). Acetaldehyde treatment did not change the chemical composition, electrophoretic mobility or the flotation characteristics of LDL. The proportion of free amino groups of AcA-LDL, ranging from 97 to 54.5%, was negatively correlated with the final concentration of AcA used in the incubation medium (r = -0.99, P less than 0.001). AcA modification of LDL accelerated its in vivo catabolism in man in such a way that the fractional catabolic rate (FCR) for AcA-LDL was negatively correlated with the percentage of free amino groups in AcA-LDL (r = -0.87, P less than 0.01). The clearance of AcA LDL modified in 0.4, 2.0, 4.0 and 8.0 mM AcA was 0.9, 1.4, 2.5 and 3.7 times faster than the clearance of C-LDL, respectively. If AcA-LDL is formed in man after ethanol ingestion, its rapid clearance may be one possible mechanism for the low LDL levels observed in chronic alcohol users. PMID- 3106049 TI - Exaggerated natriuretic response to isotonic volume expansion in hypertensive renal transplant recipients: evaluation of proximal and distal tubular reabsorption by simultaneous determination of renal plasma clearance of lithium and 51Cr-EDTA. AB - In fourteen hypertensive and fourteen normotensive renal transplant recipients, and in a group of thirteen healthy controls, changes in natriuresis, glomerular filtration rate (GFR), and tubular reabsorption of sodium were determined in relation to intravenous infusion of 2 mmol isotonic sodium chloride per kg body weight. An exaggerated natriuresis was demonstrated in the hypertensive renal transplant recipients. This new finding indicates that the augmented natriuresis following plasma volume expansion, which is a characteristic finding in subjects with arterial hypertension, is not mediated by the renal nerves. Investigation of the tubular reabsorption rates of sodium by simultaneous determination of the renal clearance of 51Cr-EDTA and lithium showed that in the hypertensives the changes in tubular handling of sodium were different from those registered in the normotensive subjects. The increased sodium excretion in the hypertensive renal transplant recipients was caused by an increased output of sodium from the proximal tubules which was not fully compensated for by an increased distal reabsorption. Whether this increased delivery of sodium to the distal segments was caused by changes in GFR or in the proximal tubular reabsorption of sodium could not be clarified in the present study and warrants further investigations. PMID- 3106050 TI - Alterations in the peritoneal transport of water and solutes during peritonitis in continuous ambulatory peritoneal dialysis patients. AB - The in situ intraperitoneal volume and the mass transfer area coefficients (MTC) of urea, lactate, creatinine, glucose, kanamycin, inulin, beta 2-microglobulin, albumin and IgG were studied in eight continuous ambulatory peritoneal dialysis (CAPD) patients. All patients were studied during a 4-h dialysis dwell, first during peritonitis and subsequently after recovery from the infection. The maximal intraperitoneal volume was reached at 68 min during peritonitis and at 150 min in the study after recovery (P less than 0.01), suggesting increased water transport during the infection. For all investigated solutes MTCs were higher in the presence of peritonitis than after recovery. This increase was most marked for the proteins (greater than 100%). The power curve relationships between MTCs and molecular weight indicated that peritoneal transport of the low- and middle-molecular weight solutes was determined by free diffusion and that the infection-induced rise was due to an increase in effective surface area. For protein transport restricted diffusion was found. The increase of this transport during peritonitis was probably caused by both a larger effective surface area and a higher vascular permeability. PMID- 3106051 TI - A new model to assess deoxycholic acid metabolism in health using stable isotope dilution technique. AB - A model has been developed that permits calculation of the absorption rates of newly formed and deconjugated deoxycholic acid (DCA) from the intestine, the fractional absorption rate of deconjugated DCA and the daily rate of formation of DCA. The model is based on steady state conditions and isotopic equalities of conjugated DCA in blood and in the enterohepatic circulation, as well as between unconjugated DCA in blood and in the intestinal content. The model requires measurement of isotopic enrichment in the conjugated and unconjugated fractions of DCA in serum after administration of an isotopic label. The measurements were carried out in seven healthy volunteers using capillary gas chromatography/mass spectrometry after oral administration of 24-13C-DCA. Intestinal absorption of deconjugated DCA exceeded that of newly formed DCA: (mean +/- SD) 7.4 +/- 5.6 vs. 4.5 +/- 2.1 mumol kg-1 d-1. Total absorption of unconjugated DCA (11.9 +/- 6.9 mumol kg-1 d-1) accounted for approximately 6% of estimated total intestinal DCA absorption. The fractional absorption rate of unconjugated DCA in the intestine averaged 55.5 +/- 15.1%; 8.2 +/- 3.3 mumol kg-1 d-1 DCA were formed daily by 7 alpha-dehydroxylation of cholic acid. This rate of DCA formation compares well with values for fecal DCA excretion (15 mumol kg-1 d-1) and cholic acid synthesis rate (11.9 mumol kg-1 d-1) obtained in comparable controls by the same laboratory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106052 TI - Effects of vitamin E therapy on ethanol-induced changes in platelet aggregation, thromboxane formation, factor VIII levels and serum lipids. AB - A transient increase in platelet thromboxane formation has been observed in non alcoholics during acute ethanol intoxication and in alcoholics shortly after ethanol withdrawal. Whether these effects are related to the generation of free radicals and lipid peroxidation was investigated by using vitamin E as a free radical scavenger and inhibitor of lipid peroxide formation. The results demonstrate that a high dose of vitamin E (1800 IU) taken daily by non-alcoholic men slightly (P less than 0.05) decreases aggregation-associated platelet thromboxane formation during ethanol oxidation. Likewise, vitamin E prevents the ethanol-induced increase (P less than 0.01) in factor VIII coagulant activity. These observations suggest that the enhancement of platelet thromboxane formation and factor VIII coagulant activity by acute ethanol ingestion may be related to stimulated lipid peroxidation. By contrast, similar effects of vitamin E were not found in alcoholics shortly after ethanol withdrawal suggesting other mechanisms for their platelet hyperreactivity. PMID- 3106053 TI - Increased levels of platelet-activating factor in blood from patients with cirrhosis of the liver. AB - The levels of platelet-activating factor (paf-acether) were measured in blood and ascitic fluid from cirrhotic patients and in blood from a group of controls, using a recently described technique for extraction and measurement. In addition, activity of acetylhydrolase, the main catabolic enzyme for paf-acether, was also measured. The highest levels of paf-acether in blood were found in decompensated cirrhotics (1.78 +/- 0.62 ng ml-1; mean +/- SD, n = 8). Compensated cirrhotics showed lower blood values (0.79 +/- 0.21, n = 4), but higher than controls (0.20 +/- 0.04, n = 12). Paf-acether levels in ascitic fluid were similar to those of blood. Values of acetylhydrolase in serum were similar in all the groups studied (3.0 +/- 0.4 in cirrhotics vs. 2.3 +/- 0.4 nmol min-1 mg-1 of protein in controls). These data suggest an enhanced production of paf-acether in cirrhotic patients rather than a decreased catabolism. High levels of paf-acether in blood could be involved in the impaired haemodynamics of cirrhotic patients and in their renal function alterations. PMID- 3106055 TI - Type 1 (insulin-dependent) versus type 2 (non-insulin-dependent) diabetes mellitus: characterization of serum lipoprotein alterations. AB - Serum lipoprotein lipids and apolipoproteins A-I, B, and E were investigated in Type 1 (insulin-dependent) diabetics, Type 2 (non-insulin-dependent) diabetics, and two control groups, twenty subjects each. Lipoproteins were separated and analysed by common methods, apolipoproteins were measured by endpoint immunonephelometry. Compared with controls, Type 2 diabetics had increased serum apolipoprotein E levels (0.116 +/- 0.020 vs. 0.079 +/- 0.014 g 1-1, P less than 0.01) together with an increased content of cholesteryl ester-enriched very low density lipoproteins. Furthermore, Type 2 diabetics had higher apolipoprotein B concentrations (1.06 +/- 0.21 vs. 0.85 +/- 0.21 g l-1 P less than 0.01), but lower high-density lipoprotein cholesterol concentrations than the controls. Conversely, Type 1 diabetics had elevated serum apolipoprotein A-I values vs. controls and Type 2 diabetics (1.70 +/- 0.33 vs. 1.49 +/- 0.22 and 1.43 +/- 0.21 g 1-1, P less than 0.01). It is concluded that Type 2 diabetics, like other groups at risk for atherosclerotic diseases, are characterized by an increased concentration of partly catabolized very low-density lipoproteins. Sufficiently insulinized Type 1 diabetics have, on the other hand, an increased number of high density lipoprotein particles. PMID- 3106054 TI - Collagen metabolism in normal and complicated pregnancy: changes in the aminoterminal propeptide of type III procollagen in serum. AB - The turnover of type III collagen, a major constituent of the myometrium and the uterine cervix, during pregnancy was evaluated by monitoring serum antigens related to the aminoterminal propeptide of type III procollagen. Their concentration increased markedly towards term in most uncomplicated pregnancies, while their size distribution throughout the pregnancy resembled that seen in the sera of normal healthy persons. In some patients, however, the level remained low, indicating interindividual variation in the release into serum and metabolism of the propeptide. There were no distinct changes during or immediately after vaginal delivery. Values exceeding the reference range for uncomplicated pregnancies were found during weeks 28-37 in patients with pre eclampsia, essential hypertension, intrahepatic cholestasis of pregnancy or twin pregnancy. Thus, pregnancy should be taken into account when evaluating results of the serum assay for the aminopropeptide and the use of this assay as an indicator of pregnancy complications warrants further study. PMID- 3106057 TI - Abstracts and index of the 21st annual meeting of the European Society for Clinical Investigation. March 21-24, Copenhagen-Elsinore, Denmark. PMID- 3106056 TI - High content of dietary linoleic acid does not reduce platelet reactivity in patients with hyperlipoproteinaemia. PMID- 3106058 TI - Blocking of interleukin 2 (IL 2) binding to the IL 2 receptor is not required for the in vivo action of anti-IL 2 receptor monoclonal antibody (mAb). I. The production, characterization and in vivo properties of a new mouse anti-rat IL 2 receptor mAb that reacts with an epitope different to the one that binds to IL 2 and the mAb ART-18. AB - A mouse anti-rat interleukin 2 (IL 2) receptor (IL 2R) monoclonal antibody (mAb), ART-65, has been developed. As shown by fluorescence-activated cell sorter analysis and immunoprecipitation studies, ART-65 recognizes in a species-specific manner the same molecule as does ART-18, a mAb which has been shown previously to recognize the rat receptor for IL 2. ART-65 and ART-18 do not competitively inhibit the binding of each other to activated T cells. ART-65, in contrast to ART-18, does not inhibit the binding of IL 2 to cells nor does it have any inhibitory effect in vitro on IL 2-driven proliferation of rat T lymphoblasts. Therefore, ART-65 is another mAb recognizing the rat IL 2 receptor, but binding to an epitope distinct from that recognized by either IL 2 or ART-18. We compared the in vivo activity of the mAb ART-65 and ART-18 with that of the W3/25 mAb in a local graft-vs-host reaction (GVHR). Similar to the anti-W3/25 treatment, ART-65 and ART-18 inhibited GVHR. The results demonstrate that GVHR depends on a small subpopulation of IL 2R+ cells present in the W3/25+ T cell population because IL 2R-targeted therapy was as effective as the treatment with W3/25 mAb which reacts with the entire T helper cell population. Moreover, the results argue against the possibility that anti-IL 2R mAb act via blockade of the IL 2 binding to IL 2R+ cells and/or by inhibiting the IL 2-driven expansion of the antigen-activated clones. The results support the view that IL 2R-targeted therapy results in the elimination of the IL 2R+ cells. PMID- 3106059 TI - Enumeration of T cells reactive with Mycobacterium tuberculosis organisms and specific for the recombinant mycobacterial 64-kDa protein. AB - The major goal of the present study was to develop a limiting dilution system for the enumeration of T cells which respond to mycobacterial antigens. Purified T cells from M. tuberculosis-immune mice were restimulated with mycobacterial antigens and accessory cells, and after 4 days expanded with antigen, accessory cells and T cell growth factor. After another 3 days, proliferative responses were determined. Similar cultures performed without antigen served as controls. Limiting dilution analysis revealed that approximately 1/2000 to 1/3000 T cells from M. tuberculosis-immune mice responded to whole M. tuberculosis organisms while T cells from normal mice did not respond. Similar T cell numbers reacted with several mycobacterial strains indicating expression of shared T cell antigens. Using a semi-purified recombinant 64-kDa protein from M. bovis the frequency of T cells generated after immunization with M. tuberculosis which reacted with a single mycobacterial protein could be estimated. We found that approximately 1/5 of the M. tuberculosis-reactive T cells recognized this particular antigen. Immunization with the recombinant 64-kDa protein in an adjuvant containing trehalose dimycolate, monophosphoryl lipid A and mycobacterial cell wall skeleton stimulated an equally high number of M. tuberculosis-reactive T cells (1/2000). These findings demonstrate that a high proportion of tuberculosis-responsive T cells are directed against the 64-kDa protein and that immunization with this antigen in an appropriate adjuvant system is capable of stimulating high numbers of M. tuberculosis-reactive T cells. Limiting dilution analysis with a panel of mycobacterial proteins or peptides may allow their ranking from immunodominant to immunosilent and facilitate identification of antigens or epitopes relevant to protection. PMID- 3106060 TI - High connectivity, natural antibodies preferentially use 7183 and QUPC 52 VH families. AB - Twenty-seven B cell hybridomas derived from spleen cells of nonimmunized, 6-day old BALB/c mice and previously characterized serologically were screened for VH gene expression: hybridomas expressing the two most D-proximal VH-gene families, 7183 and QUPC 52 were over-represented in this sample. Strikingly, clones serologically characterized by high degree of degenerate "specificity" and high idiotypic connectivity were found to use almost exclusively these two VH-gene families. As these serological properties are a unique feature of "natural" antibody repertoires, the results may reflect a functional relationship between expression of these VH genes and activation of B cells in the internal environment, particularly in the context of idiotypic interactions. PMID- 3106061 TI - Antibody diversity in amphibians. Noninbred axolotls used the same unique heavy chain and a limited number of light chains for their anti-2,4-dinitrophenyl antibody responses. AB - Noninbred axolotls (Ambystoma mexicanum, amphibia, urodela) were immunized with trinitrophenylated sheep red blood cells (TNP-SRBC) and anti-2,4-dinitrophenyl (DNP)/TNP antibodies were individually purified by affinity chromatography. The isolated IgM-like antibodies were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing (IEF) under reducing conditions. The SDS-PAGE and IEF-separated heavy (H) and light (L) chains were electroblotted onto nitrocellulose, probed with mouse monoclonal antibodies specific for H or L axolotl Ig chains and stained by a rabbit anti mouse Ig horseradish peroxidase conjugate. The specific detection of axolotl anti DNP/TNP H chain spectrotypes shows for each of the 14 individually analyzed samples a very similar pattern of 4-5 ordered spaced bands. This suggests that all animals express the same VH chain segment representing the germinal expression of a unique VH gene. When the same analysis was performed starting from a pool of nonimmunized axolotl sera, a low background of natural anti-DNP antibodies was detected. When analyzed by IEF, the H chains of the pooled anti DNP natural antibodies display the same pattern of restricted heterogeneity when compared to the H chain spectrotypes of the individual immune anti-DNP/TNP antibodies. The specific detection of the axolotl anti-DNP/TNP L chain spectrotypes indicates at the individual level more heterogeneous and polymorphic patterns compared with H chains, although most animals share the majority of their bands. Our experiments indicate that in axolotl, the production of antibodies to DNP results from the germinal expression of a very limited set of V genes, already expressed as naturally occurring anti-DNP antibodies before immunization. This seriously restricts the possible extension of the antibody repertoire and perhaps even the nature of antibody "specificity" in this primitive vertebrate. PMID- 3106062 TI - Ir gene control of the murine secretory IgA response to cholera toxin. AB - In these experiments we examined the genetic control of the secretory IgA (sIgA) response to cholera toxin (CT) after CT feeding. Inbred, congenic and intra-H-2I region recombinant mouse strains were immunized with intragastric application of 10 micrograms CT on days 0 and 14. Samples of intestinal secretions and plasma were collected 1 week after the second dose and antibodies to CT measured in them by antigen- and isotype-specific enzyme-linked immunosorbent assay. In three different sets of H-2-congenic strains the intestinal IgA anti-CT response clearly depended on the H-2 haplotype rather than on background or IgH genes. H 2b (B10, A.BY/SnJ, C3H.SW) and H-2q (B10.T(6R), DBA/1J) strains were high responders, H-2k (B10.BR, C3H/He), H-2s (A.SW/SnJ) and H-2d (B10.D2) strains were low responders. Within the H-2 complex the intestinal IgA anti-CT response was mapped to the I-A subregion with the use of congenic intra-H-2I region recombinant strains: B10.A(3R) and B10.A(5R) were high responders and B10.A(4R), B10.MBR and B10.GD were low responders. Plasma IgG anti-CT after CT feeding paralleled the sIgA results. Surprisingly, the sIgA and plasma IgG anti-CT responses in individual mice of the various strains tested showed a highly significant positive correlation. We conclude that both the sIgA response and plasma IgG anti-CT response after CT feeding is controlled by the I-A subregion of H-2. PMID- 3106064 TI - Provision of the immunoglobulin heavy chain enhancer downstream of a test gene is sufficient to confer lymphoid-specific expression in transgenic mice. AB - To test whether the immunoglobulin heavy chain enhancer is sufficient to direct lymphoid specific gene expression in vivo, we have incorporated into the mouse germ line a test gene (chloramphenicol-acetyl transferase) whose transcription is potentiated by the enhancer. Analysis of transgenic mice bearing single-copy integrations of the injected DNA indicates that provision of the enhancer downstream of the test gene (beyond the polyadenylation site) is sufficient to direct lymphoid-specific expression. The tissue specificity is considerable as judged by the fact that transgene expression is at least one thousandfold higher in spleen than in liver. Within the lymphoid family, expression of the transgene is much higher in surface IgM+ spleen cells than in thymocytes high in Thy-1 expression, suggesting that the enhancer preferentially directs expression to cells of the B lineage. PMID- 3106063 TI - Accessory molecules and T cell activation. II. Antibody binding to L3T4a inhibits Ia-independent mouse T cell proliferation. AB - Monoclonal antibody (mAb) blocking assays using L3T4- and lymphocyte function associated antigen-1 (LFA-1)-specific reagents were used as an approach to investigate the involvement of these accessory molecules in various T cell activation pathways. As previously reported, rat mAb to L3T4a and LFA-1A functional epitopes efficiently blocked antigen-driven T helper cell proliferation. In contrast, antigen- and Ia-independent T cell triggering induced by appropriate mAb to the Thy-1 or the T cell receptor molecules were found to be inhibitable by L3T4a- but not LFA-1A-specific mAb, although the extent of inhibition varied, depending on the cell type and the activating signal examined. These results provide further evidence that the inhibiting effects of L3T4 specific mAb on T cell responses may be due, in addition to an impairment of L3T4 class II major histocompatibility complex molecular interaction, to a down regulatory signal possibly transmitted by the L3T4 molecule itself. PMID- 3106065 TI - Thymic immune response gene function in radiation chimeras reconstituted with purified hemopoietic stem cells. AB - Thymectomized (C57BL/6[B6] X bm1)F1 mice and thymectomized (B6 X bm12)F1 mice were engrafted with neonatal parental thymus of either B6 type [H-2b mouse, Sendai virus cytotoxic T cell (Tc) responder] or bm1 type (H-2Kb mutant, Sendai virus Tc nonresponder) and B6 type (H-Y Tc responder) or bm12 type (H-2 I-Ab mutant, H-Y Tc nonresponder), respectively. All mice were irradiated and reconstituted with highly purified syngeneic pluripotent hemopoietic stem cells. All types of thymus engraftment resulted in a restored T cell immunocompetence. The Tc reaction to Sendai virus in (B6 X bm1)F1 mice engrafted with both responder type B6 and nonresponder, type bm1 neonatal thymus allowed maturation of Sendai-specific, H-2Kb-restricted Tc. For the Tc reaction to H-Y, only responder type B6 thymus restored the Tc response, whereas this was not achieved with nonresponder type bm12 thymuses. We conclude from this study that in this radiation stem cell chimera system the radioresistant component of the thymus dictates major histocompatibility complex (MHC) specificity and immune response phenotype of T cells restricted to class II MHC molecules but not of T cells restricted to class I MHC molecules. PMID- 3106066 TI - In vitro studies on human IgD. II. IgD-secreting cells preferentially elaborate IgD, lambda molecules. AB - The "IgD paradox" describes the unexpected finding that, despite a predominance of kappa (kappa) light (L) chains on the surface of IgD+ human B cells, the majority of monoclonal IgD proteins are of lambda (lambda) type. This potentially informative phenomenon appears to be based on a preferential association between delta (delta) heavy (H) and lambda L chains of IgD-secreting cells. The current studies analyze the phenomenon in vitro. Initial assays on tonsil "spent" supernatants showed that the higher IgD-"externalizing" cultures displayed progressively elevated IgD, lambda/kappa ratios due to parallel shifts in total IgD and IgD, lambda while IgD, kappa remained stable. The cells of the same higher-IgD cultures demonstrated that individual IgD-containing cells had a predominance of lambda chains in contrast to IgM-containing cells of the same cultures using fluorochrome-antibody double staining. Certain tonsil culture IgD containing cells remarkably appeared to have exclusively lambda chain. These same tonsils show evidence of IgD secretion (Litwin, S. D. and Zehr, B. D., Eur. J. Immunol. 1987. 17:483); thus, these data align preferential delta-lambda chain association with IgD-secreting normal tonsil B cells in vitro and emphasize the usefulness of IgD, lambda/kappa ratio in monitoring IgD secretion. In another approach the relationship between the cellular location of IgD and the preferential delta-lambda chain association was studied using Triton X-114 partitioned cell lysates. IgD, lambda/kappa ratios were one or less in the detergent phase (membrane-enriched fraction) consistent with expected IgD, kappa predominance in membrane IgD. In contrast, the aqueous phase (intracellular enriched fraction) of IgD-secreting cultures had 2-4 times higher supernatant IgD, lambda/kappa ratios. The restriction of high IgD, lambda/kappa ratios to intracellular fractions and supernatants of IgD-secreting cultured cells parallels the predicted distribution of secretory IgD. In sera studies, the correlation between total IgD and IgD, lambda/kappa ratio values was consistent with secreted sera IgD showing preferential lambda chain expression. It was concluded that the phenomenon of delta-lambda chain preferential association is expressed in vitro as well as in vivo; a property of normal, nonmalignant human IgD-secreting B cells; and closely related to the secretory form of IgD. In certain cultures, the delta-lambda chain preference was so striking as to imply limited heterogeneity of the IgD immune response. PMID- 3106067 TI - Cross-linking of the T cell receptor complex with the subset-specific differentiation antigen stimulates interleukin 2 receptor expression in human CD4 and CD8 T cells. AB - Nonpolymorphic interactions between the T cell differentiation antigens CD4 or CD8 and major histocompatibility complex (MHC)-encoded molecules have been postulated to participate in antigen recognition of MHC-restricted T cells. This would imply simultaneous binding of CD4/8 and of the T cell receptor complex (Ti/CD3) to MHC molecules on the stimulator or target cell. In this report experimental evidence is provided that simultaneous binding by antibodies of Ti/CD3 and of CD4 or CD8 leads to the expression of interleukin 2 (IL 2) receptors in resting human T cells and to their subsequent proliferation in the presence of recombinant IL 2 (rIL 2). This could be shown by using a novel anti CD3 monoclonal antibody (BMA 030) which alone only marginally stimulates highly purified human T cells even when applied in cross-linked form. However, human T cell subpopulations could be stimulated to grow in the presence of rIL 2 when BMA 030 was fixed to a solid support in combination with antibodies to either CD4 or CD8. In limiting dilution experiments, the frequencies of CD4 and CD8 T cells activated by the antibody combinations were similar to those activated by phytohemagglutinin in the presence of irradiated adherent cells. No stimulation was achieved if both or one antibody was applied in soluble form. In contrast, soluble antibodies inhibited activation by solid-phase antibodies. Taken together, cross-linking of Ti/CD3 with CD4/8 seems to be essential for T cell activation in cases of ligands that bind but do not activate T cells on their own -a situation that may reflect the interaction of T cell receptors with MHC encoded molecules in association with antigen. PMID- 3106069 TI - Complement activation by IgM: evidence for the importance of the third constant domain of the mu heavy chain. AB - We have isolated and analyzed the DNA encoding the mu heavy chain constant region of a mutant IgM which is defective in initiating complement-dependent cytolysis. By assaying the expression of mu genes which were constructed in vivo from mutant and normal gene segments, we have mapped the mutation into a 555-base pair segment. In this segment there is one nucleotide change, such that the mutant mu gene encodes serine rather than the normal proline at amino acid position 436 in the third constant domain. We have used site-directed mutagenesis to revert this mutation to the normal sequence and shown that this substitution results in the production of IgM with the normal phenotype. PMID- 3106068 TI - The response of selected human B cell lines to B cell growth and differentiation factors. AB - Fifteen human B cell lines were tested for their ability to respond to B cell growth and differentiation factors present in phytohemagglutinin-conditioned medium. Five lines responded significantly: CESS showed an increase in IgG production only, HFB1 and BALM1 showed an increase in proliferation only and L4 and BALM4 showed an increase in both IgG production and proliferation. When four of the responding lines (CESS, HFB1, L4 and BALM4) were cultured with human recombinant-derived interleukin 1, interleukin 2, interleukin 4 or interferon gamma no significant response was seen. CESS, L4 and BALM4 all increased IgG production in response to partially purified B cell growth factor (Cellular Products, Inc., Sera-Lab., Crawley Down, GB) and B cell differentiation factor containing supernatant from the T24 bladder carcinoma cell line. HFB1, L4 and BALM4 all showed increased tritiated thymidine incorporation in response to purified B cell growth factor but not in response to B cell differentiation factor-containing supernatant. These lines may prove useful in the study of B cell growth and differentiation factors and their receptors. PMID- 3106070 TI - Differentiation in the murine B cell lymphoma I.29: individual mu + clones may be induced by lipopolysaccharide to both IgM secretion and isotype switching. AB - Cells from the monoclonal B cell lymphoma I.29 expressing surface IgM (mu +) are capable of differentiating in vitro to IgM secretion and of switching to IgA or IgE production in response to lipopolysaccharide (LPS) stimulation. To determine whether a single mu + B cell is capable of undertaking both differentiative pathways (isotype switch and plasma cell differentiation) I.29 mu + cells were cloned by limiting dilution and a panel of clones were analyzed by immunofluorescence, endogenous labeling and Northern blotting. While 100% of the clones could differentiate toward IgM secretion, only a proportion of them (greater than 70%) also switched to IgA and/or IgE production. Certain clones switched preferentially to a specific isotype. Taken together with the observation that C gamma genes were never the target of switching in our experiments, these data suggest that individual mu + clones from the I.29 lymphoma are "precommitted" as for their switching potentials. The subclones that showed a high frequency of switching to IgA transcribed the germ line C alpha gene(s), suggesting a role for chromatin structure in determining the isotype switch specificity. Switch variant clones expressing either IgA or IgE on the cell surface were isolated and found capable of further differentiating toward Ig secretion in response to LPS. On the contrary, we could not induce switch to IgA in IgE-producing cells. Unlike mu + and alpha + cells, all the switch variant clones expressing IgE tested by endogenous labeling constitutively secreted large amounts of IgE in the supernatants even in the absence of LPS stimulation. PMID- 3106071 TI - Comparison of the effects of 1,25-dihydroxyvitamin D3 on T lymphocyte subpopulations. AB - Previous studies have demonstrated that 1,25-dihydroxyvitamin D3 (calcitriol) is a potent inhibitor of human T lymphocyte proliferation. It has been reported that only CD4+ cells are sensitive to the anti-proliferative action of calcitriol. To further evaluate this observation, we first performed cell cycle analysis of unfractionated phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMC) in the absence or presence of calcitriol. The CD4/CD8 ratio was similar between control and treated cells for each phase of cycle (G0----G1, S, G2 + M), suggesting that calcitriol did not selectively block proliferation of either T cell subpopulation. Secondly, the growth-inhibitory activity of calcitriol on PBMC selectively depleted of either CD4+ or CD8+ cells was comparable to that observed with unfractionated PBMC. Furthermore, the induction of transferrin receptors was inhibited by calcitriol to a comparable degree in each T cell subset, suggesting that equivalent inhibition of transition into late G1 was observed. Finally, calcitriol inhibited the proliferation of highly purified T cell subsets (greater than 99% pure) to equivalent degrees. These data suggest that T cell subsets defined by either the CD4 or by the CD8 antigen are both sensitive to the growth inhibitory effects of calcitriol. PMID- 3106073 TI - Presence of c-fos-like immunoreactivity in the adult rat brain. PMID- 3106072 TI - Expression of the bcl-2 gene in mouse B lymphocytic cell lines is differentiation stage specific. AB - cDNA clones of mouse bcl-2 have been isolated and characterized by homology to the human bcl-2 gene, a putative oncogene that is found on the portion of chromosome 18 characteristically involved in the t(14;18) translocation present in nearly all human follicular B cell lymphomas. Our mouse cDNA clone detects 7.9 and 6.3-kb bcl-2 RNAs in mouse B cell lymphomas, but only in tumors consisting of pre-B and follicular center mature B cells, not in pro-B cell or plasma cell tumors. Thus, this gene appears to be a B cell differentiation marker that is expressed only in committed B cells, but is shut off in end stage plasma cells. This pattern of expression is unique among oncogenes, and we suggest that it may be responsible for the high frequency of translocations at this locus in the common malignancy of human mature B cells, follicular lymphomas. PMID- 3106074 TI - Modulation of arterial smooth muscle cells from contractile to synthetic phenotype requires induction of ornithine decarboxylase activity and polyamine synthesis. AB - The role of polyamines in modulating cultivated arterial smooth muscle cells from contractile to synthetic phenotype was studied by biochemical and electron microscopic methods. Ornithine decarboxylase (ODC), the first and overall rate limiting enzyme in polyamine biosynthesis, showed no detectable activity in freshly isolated contractile cells, rose to a peak of activity after 2 days of culture, simultaneously with the most rapid phase of phenotypic modulation, and thereafter returned to a lower level of activity. The increase in ODC activity was accompanied by a gradual rise in the cellular concentrations of the polyamines putrescine, spermidine and spermine. The polyamine synthesis inhibitors alpha-difluoromethylornithine and methylglyoxal-bis(guanylhydrazone) prevented transition into synthetic phenotype as well as initiation of cell growth. The results indicate that polyamines play an important role in the control of smooth muscle phenotype and growth. PMID- 3106075 TI - Induction of ornithine decarboxylase activity and putrescine synthesis in arterial smooth muscle cells stimulated with platelet-derived growth factor. AB - Cultivated arterial smooth muscle cells were used to study the effects of platelet-derived growth factor (PDGF) on polyamine synthesis and of polyamine synthesis inhibitors on initiation of DNA synthesis by PDGF. Quiescent (serum starved) cells showed no detectable activity of ornithine decarboxylase (ODC), the first and overall rate-limiting enzyme in polyamine synthesis, and had low levels of the polyamines putrescine, spermidine and spermine. PDGF caused a marked increase in ODC activity, with a peak after 6 h followed by a rapid decline. The rise in enzyme activity was blocked by actinomycin D and cycloheximide, suggesting control at the transcriptional and translational levels, alpha-Difluoromethylornithine (DFMO), a catalytic and irreversible inhibitor of ODC, prevented the appearance of enzyme activity. The cellular content of putrescine increased distinctly in response to PDGF, with a peak after 8 h, abolished by simultaneous treatment with DFMO. In contrast, the concentrations of spermidine and spermine changed but little within the 20-h period examined here. DFMO inhibited the initiation of DNA synthesis without affecting the length of the prereplicative lag phase and was fully active if added within 4 h after PDGF. The effect of DFMO on DNA synthesis was counteracted by addition of polyamines to the culture medium and exogenous polyamines were also found to stimulate DNA synthesis in PDGF-free medium (spermine greater than spermidine greater than putrescine). It is concluded that induction of ODC and putrescine synthesis are integral parts in the mitogenic response of arterial smooth muscle cells to PDGF. PMID- 3106077 TI - Effect of recombinant gamma interferon on chronic myelogenous leukemia bone marrow progenitors. AB - In order to understand its mechanism of action and explore its potential as a therapeutic agent, we studied the effect of recombinant gamma interferon (IFN) on in vitro proliferation and on karyotype of bone marrow-derived hematopoietic stem cell progenitors (BFUe, CFUmix) obtained from patients with Ph1-positive chronic myelogenous leukemia (CML). Addition of IFN to culture resulted in a dose dependent inhibition of both normal and CML BFUe and CFUmix. The maximum dose dependent suppression of CML BFUe (92% +/- 4%) and CML CFUmix (100%) exceeded the maximum suppression of normal BFUe (40% +/- 4%) and normal CFU mix (68% +/- 6%) (p less than 0.001 and p = 0.008). In parallel studies, CML BFUe and CFUmix were cultured with and without IFN, and cells recovered from culture were examined cytogenetically. Treatment of CML bone marrow cells (BMC) with IFN resulted in an increase in the proportion (p less than 0.001) of Ph1-negative metaphases when compared to control cells grown in the absence of IFN. Recombinant gamma interferon has a significant antiproliferative effect against CML bone marrow derived stem cell progenitors in vitro, and the addition of this agent to culture increases our ability to identify a cell population derived from a Ph1-negative progenitor pool. Recombinant gamma interferon may selectively spare Ph1-negative hematopoietic progenitors, and may be an active agent in the treatment of CML. PMID- 3106076 TI - In vitro retroviral transfer of ras genes to single hemopoietic progenitors. AB - Recent studies have shown that retroviruses can serve as efficient vectors of exogenous genes that can be inserted and expressed in a variety of mammalian cell types. Several investigators have exposed total bone marrow populations to retroviruses in vitro and have demonstrated the presence of exogenous genes after inoculation into irradiated mice. Our approach was to identify individual pluripotent hemopoietic progenitors in vitro and to use these single cells as targets for retroviral gene transfer. This approach was made possible by our previous identification of in vitro colonies containing pluripotent, undifferentiated blast cells with very high secondary replating efficiencies. By using a monoclonal antibody to detect the product of the transferred gene, we were able to document infection of single multipotent cells and to quantitate the percentage of the progeny cells that expressed the transferred gene. Specifically, individual blast cells were obtained by micromanipulation, exposed to Harvey sarcoma virus, and ras gene expression was detected by immunofluorescence in individual colonies. A variety of types of p21-positive colonies were seen, including a macrophage (m)-neutrophil (n)-erythroid (E)-mast cell (mast)-megakaryocyte (M) colony, an mEmastM colony, an nmmast colony, mnE colonies, mn colonies, and m colonies. These results demonstrated that multipotent progenitors were recipients of exogenous genes and that these genes were expressed in the differentiated progeny. Initial experiments failed to demonstrate that the cells in the infected colonies were transformed. Retroviral infection of isolated blast cells may provide a unique method for studies of the effects of a variety of genes, including oncogenes, in hemopoietic cells. PMID- 3106078 TI - Changes in phrenic, mylohyoid, and hypoglossal nerve activities that follow intravenous infusions of aminophylline. AB - We determined whether or not administrations of aminophylline would produce differential changes in activities of the hypoglossal nerve and the mylohyoid branch of the trigeminal nerve, compared with phrenic nerve activity. The former two nerves innervate muscles influencing the upper airway, whereas the phrenic nerve innervates the diaphragm, a major muscle of the ventilatory pump. Neural activities were recorded in decerebrate, vagotomized, paralyzed, and ventilated cats. Peak integrated phrenic activity generally increased with intravenous infusions of cumulative doses of aminophylline ranging from 1.0 to 64 mg/kg. The concomitant changes in trigeminal and hypoglossal activities were extremely variable. In some animals, peak integrated trigeminal and/or hypoglossal activities rose progressively with increasing doses of aminophylline. For other animals, maximum levels of neural activities were attained at intermediate doses and declined at higher dose levels. Results were similar in animals having bilateral sections of the carotid sinus nerves. The variable changes in neural activities may reflect the multiple sites of action of aminophylline in the brain stem. PMID- 3106079 TI - Trichinella spiralis: behavior, structure, and biochemistry of larvae following exposure to components of the host enteric environment. AB - Four layers are present on the surface of infective larvae of Trichinella spiralis isolated from host muscle in pepsin-HCl. Trypsin treatment of pepsin-HCl isolated worms caused partial degradation and removal of large patches of the two outer surface layers. Following exposure to bile, only traces of the outer layers remained on the worms surface. These changes in the worm surface were accompanied by a shift from Type I behavior, typical of pepsin-HCl isolated larvae, to Type II behavior, (snakelike) following exposure to either trypsin or bile. Worm behavior was also temperature dependent. Type I behavior was typical of worms maintained at room temperature regardless of treatment, while Type II behavior displayed by worms held at 37 C was treatment dependent. The absorption of in vitro glucose or beta-methyl-D-glucoside was lowest in pepsin-HCl isolated first stage infective larvae, significantly higher in trypsin treated worms and greatest in worms following exposure to bile. Sugar uptake by worms isolated from the host small intestine after 1 hr of enteral infection was similar to that seen in worms isolated from host muscle in pepsin-HCl. Sugar uptake in vitro in worms 2 hr following enteral infection was similar to worms following exposure to bile. The highest levels of sugar absorption in vitro occurred in worms which had resided in the small intestine for 3 hr. The lowest rates of incorporation of label into worm tissues was seen in 1 hr enteral and pepsin-HCl isolated worms. Infective larvae treated with trypsin or bile incorporated significantly greater amounts of label than the two former groups. The highest levels of incorporation of label into worm tissues was seen in 3 hr enteral worms. These findings support the view that trypsin, bile, and temperature serve as environmental cues which lead to alteration of the parasite's behavioral and nutritional status. PMID- 3106081 TI - Photoreactivation of UV damage in cultured Drosophila cells. AB - Cell survival and photoreactivation of 254 nm ultraviolet (UV) light damage in a wild type Drosophila cell line was assayed by colony formation in liquid medium. Fo, Fq, and extrapolation number for the exponential portion of survival curves are 21 J/m2, 3.6 J/m2, and 1.5 for non-photoreactivated cells and 110 J/m2, 11.2 J/m2, and 1.3 for those exposed to photoreactivating light. Maximal photoreactivation occurs at the 100 J/m2 region of the curve. At 10 and 50% survival, 75-80% of the UV damage was photoreactivable. PMID- 3106080 TI - Cross-reactive monoclonal antibodies to alcohol dehydrogenases. AB - Three anti-horse liver alcohol dehydrogenase (HLADH) monoclonal antibodies are described. Two are specific for ADH and cross-react with class I and II enzymes from mouse, horse and Chinese hamster. They are specific for the native enzyme but do not inhibit enzyme activity except when combined at high concentration. The third antibody was isolated as a response to rabbit metallothionein. It binds metalloproteins and inhibits ADH activity. PMID- 3106082 TI - Insulin but not phorbol ester treatment increases phosphorylation of vinculin by protein kinase C in BC3H-1 myocytes. AB - Insulin was found to increase protein kinase C activity in BC3H-1 myocytes as determined by in vitro phosphorylation of both a lysine-rich histone fraction (histone III-S) and vinculin. TPA treatment for 20 min or 18 h provoked an apparent loss of histone-directed but not vinculin-directed phosphorylation by cytosolic C-kinase. Thus, chronic TPA-induced 'desensitization' or 'depletion' of cellular protein kinase C is more apparent than real, and is not a valid means for evaluating the role of C-kinase in hormone action. PMID- 3106083 TI - Luteinizing hormone-releasing hormone (LHRH)-induced arachidonic acid release in rat granulosa cells. Role of calcium and protein kinase C. AB - In rat granulosa cells prelabeled with [3H]arachidonic acid, addition of LHRH, A23187 or 12-0-tetradecanoyl phorbol-13-acetate (TPA) enhanced the release of [3H]arachidonic acid into the culture medium. The effect of A23187 was significant as early as 5 min and the lowest effective dose was 5 X 10(-8)/M. On the other hand, TPA was effective only at dosages greater than 10(-6)M. These results suggest that the stimulatory effect of LHRH on arachidonic acid release is coupled more tightly to a Ca2+-dependent rather than a protein kinase C mediated pathway. PMID- 3106084 TI - Stimulus-response coupling in a cell-free platelet membrane system. GTP-dependent release of Ca2+ by thrombin, and inhibition by pertussis toxin and a monoclonal antibody that blocks calcium release by IP3. AB - The Ca2+-mobilizing action of thrombin was demonstrated in a cell-free platelet membrane system consisting of open sheets of plasma membrane plus sealed membrane vesicles that accumulate Ca2+ and release Ca2+ in response to IP3. Thrombin plus GTP, acting on plasma membrane (not vesicles), produced a soluble factor (destroyed by alkaline phosphatase) that released Ca2+ from the vesicles. This effect of thrombin/GTP was blocked by a monoclonal antibody that binds to vesicles and prevents Ca2+ release by IP3. Pertussis toxin plus NAD ADP ribosylated plasma membrane polypeptides of 39 and 41 kDa and blocked Ca2+ release by thrombin/GTP, but not by IP3. PMID- 3106085 TI - Amiloride selectively inhibits the urokinase-type plasminogen activator. AB - The diuretic drug amiloride, an inhibitor of Na+ uptake, competitively inhibits the catalytic activity of the urokinase-type plasminogen activator (u-PA), with a Ki of 7 X 10(-6) M. Generation of plasmin, cleavage of peptide substrates, and interaction of u-PA with a specific macromolecular proteinase inhibitor are all prevented in the presence of the drug. In contrast, amiloride does not affect the activity of either tissue-type plasminogen activator, plasmin, plasma kallikrein or thrombin. The inhibition of u-PA by amiloride may be related to the previously reported inhibition of u-PA-type enzymes by Na+. Amiloride or related compounds could prove useful in selectively controlling u-PA-catalyzed extracellular proteolysis. PMID- 3106086 TI - A model of the nucleotide-binding site in tubulin. AB - Tubulin uses GTP to regulate microtubule assembly and is thought to be a member of a class of GDP/GTP-binding proteins (G-proteins) as defined by Hughes [(1983) Febs Lett. 164, 1-8]. How tubulin is structurally related to G-proteins is not known. We use a synthesis of sequence comparisons between tubulin, other G proteins, and ADP/ATP-binding proteins and topological arguments to identify potential regions involved in nucleotide binding. We propose that the nucleotide binding domain in the beta-subunit of tubulin is an alpha/beta structure derived from amino acid residues approximately 60-300. Five peptide sequences are identified which we suggest exist as 'loops' that extend from beta-strands and connect alpha-helices in this structure. We argue that GDP binds to four of the five loops in an Mg2+-independent manner while GTP binds in an Mg2+-dependent manner to a different combination of four loops. We propose that this switch between loops upon GTP binding induces a conformational change essential for microtubule assembly. PMID- 3106088 TI - Apolipoprotein A-I-binding protein from human term placenta. Purification and partial characterization. AB - A protein that binds to the main apoprotein, apoA-I, of human high density lipoprotein (HDL) has been isolated from human placenta. Ligand blotting after SDS gel electrophoresis indicated that the 120 kDa protein in the absence of reducing agents binds apoA-I. If gel electrophoresis was performed under reducing conditions two main bands, approx. 50 and 30 kDa that did not bind apoA-I, were evident. In an enzyme-linked immunosorbent assay the binding protein specifically bound apoA-I, delipidated or as HDL. ApoA-II, apo E and LDL did not compete with apoA-I for binding to this protein. PMID- 3106087 TI - The generation of an organic free radical in substrate-reduced pig kidney diamine oxidase-cyanide. AB - When the cyanide complex of the copper protein, pig kidney diamine oxidase, is reduced anaerobically by cadaverine (1,5-diaminopentane), the broad, 480 nm, absorption band characteristic of the resting enzyme is bleached and a new absorption spectrum with features at 457, 429, 403 (shoulder), 360 (shoulder) and 332 nm appears. Concomitantly, the EPR spectrum of the enzyme Cu(II)-CN complex decreases in intensity and a new signal is observed that is attributable to an organic free radical. The g values and hyperfine splittings are similar to those previously assigned to a free radical observed when the cyanide complex of lentil seedling diamine oxidase is reacted with the substrate p dimethylaminomethylbenzylamine [(1984) FEBS Lett. 176, 378-380]. The optical absorption and EPR spectra of the organic radical observed in both proteins are consistent with the same semiquinone-type structure, as expected if pyrroloquinolinequinone (PQQ) is the bound cofactor found in both enzymes. PMID- 3106089 TI - Patterns of gene expression during plasmacytoid differentiation of chronic lymphocytic leukaemia cells. AB - Chronic lymphocytic leukaemia (CLL) cells may be induced to undergo plasmacytoid differentiation in vitro in response to 12-O-tetradecanoyl phorbol acetate (TPA). We show here that plasmacytoid differentiation and the accompanying accumulation of Cmu immunoglobulin mRNA are preceded by a rapid transient increase in the expression of the proto-oncogenes, c-myc and c-fos. In terminally differentiated cells the level of c-fos mRNA returned to the original basal level whilst c-myc expression remained appreciably higher than in undifferentiated CLL cells. These data support a possible role for c-fos and c-myc in the programmed chain of events that occur during terminal differentiation of B-lymphocytes. PMID- 3106090 TI - Iron binding to microsomes and liposomes in relation to lipid peroxidation. AB - The effects of ADP, ATP, citrate and EDTA on iron-dependent microsomal and liposomal lipid peroxidation, and on 59FeCl3 binding to the lipid membranes were measured. The aim was to test if initiation of lipid peroxidation is a site specific mechanism requiring bound iron. In the absence of chelator, iron was bound to both membranes. EDTA and citrate removed the iron and inhibited peroxidation. ATP and ADP stimulated peroxidation, but whereas ADP allowed only half of the iron to remain bound, all was removed by ATP. Chelators, therefore, cannot be simply influencing a site-specific mechanism. Their effects must relate to the reactivities of the different iron chelates as initiators of lipid peroxidation. PMID- 3106091 TI - Misunderstanding or misrepresentation? 'Reticulocyte lipoxygenase, ingensin, and ATP-dependent proteolysis'. PMID- 3106092 TI - A new method for the selective isolation of phosphoserine-containing peptides. AB - Meyer et al. [(1986) FEBS Lett 204, 61-66] have shown that phosphoserine can be converted to S-ethylcysteine by beta-elimination and addition of ethanethiol. I have utilised this modification to develop a rapid method for the selective purification of phosphoserine-containing peptides from complex mixtures. Changing phosphoserine to S-ethylcysteine increases the hydrophobicity of a peptide, altering its mobility during reverse-phase chromatography. The number of S ethylcysteine residues in a peptide can be quantified at the picomolar level, following acid hydrolysis and conversion to the phenylthiocarbamyl derivative. The procedure may be particularly powerful for the analysis of peptides that are phosphorylated at multiple sites in vivo. PMID- 3106093 TI - Leukocyte-derived metabolites of arachidonic acid in ischemia-induced myocardial injury. AB - Within minutes of occlusion of a major coronary artery the polymorphonuclear leukocytes (PMNs) are activated whereby they adhere to the vascular endothelium and migrate through the endothelial layer. Interactions with the endothelium can promote increased vascular resistance, diminished collateral flow, capillary blockade, and predisposition to vasospasm, as well as enhanced vascular permeability. On subsequent reperfusion entrapped leukocytes contribute to the no reflow phenomenon, while more leukocytes gain access to the previously ischemic region. The leukocytes infiltrate the myocardium where they exacerbate the process of tissue injury and the development of arrhythmias. The release of leukocyte-derived mediators including arachidonic acid (AA) metabolites and oxygen-derived free radicals probably underlies these activities of the leukocytes. PMNs contain active lipoxygenase enzymes capable of metabolizing AA to products that are not normally found in the myocardium, and can dominate the metabolic profile of that tissue, leading to changes in myocardial integrity and function. Inhibitors of the lipoxygenase enzymes suppress the accumulation of leukocytes into the ischemic myocardium and reduce infarct size. However, because the drugs prevent cell invasion it cannot be inferred that a lipoxygenase metabolite per se is deleterious to the ischemic heart, inasmuch as any leukocyte dependent mechanism of injury will be attenuated whether it is mediated by eicosanoids or by any other leukocyte-derived product. Additional studies with specific inhibitors/antagonists are required to determine the biochemical mechanisms underlying the different aspects of leukocyte-mediated myocardial injury. PMID- 3106095 TI - Oxytocin enhances thyrotropin-releasing hormone-induced prolactin release in normal menstruating women. AB - The effects of oxytocin (OT) on basal thyrotropin-releasing hormone (TRH) stimulated thyrotropin (TSH) and prolactin (PRL) secretion were evaluated in normal menstruating women during follicular, periovulatory, and luteal phases. Two different studies were performed. In one study, 15 subjects were treated with OT or saline; in the other study, 20 women were tested with TRH alone or in combination with OT. Results during follicular, periovulatory, and luteal phases were similar. OT did not produce any effect on basal serum TSH and PRL levels and on the TRH-stimulated TSH secretion, whereas it significantly enhanced the PRL response to TRH. At all examined phases during the menstrual cycle, the mean peak PRL response was reached within 20 minutes after TRH injection, and the peak was about three times higher than basal value when TRH was given alone and about four times when OT was present. These data suggest that in normal women OT is not involved in the control of basal and TRH-stimulated TSH secretion and of basal PRL release. In contrast, the enhancement of the TRH-induced PRL release suggests that OT plays a role in the control of the acutely stimulated PRL secretion. Because results were similar regardless of the phase of the menstrual cycle, estrogen and/or progesterone do not appear to be involved in the effect of OT on the TRH-induced PRL release. PMID- 3106094 TI - Prolactin response to thyrotropin-releasing hormone in women with infertility and/or randomly elevated serum prolactin levels. AB - Infertile women with normal serum prolactin (PRL) levels have been known to establish a pregnancy after the use of bromocriptine, a dopamine agonist. These data imply that there may be a group of women with a slight but significant increase in PRL secretion that may have resulted in their infertility. This study evaluates the thyrotropin-releasing hormone (TRH)-induced PRL and thyroid stimulating hormone (TSH) response in normal women (NL, n = 6), women with anovulation and/or inphase endometrial biopsies (AN/IN, n = 12), and women with histologic evidence of luteal phase deficiency (LPD, n = 12). Most of these women were found to have elevated serum PRL values on random testing. There was a statistically significant increase in PRL response at all time intervals after TRH between the NL and AN/IN groups compared with the group with LPD on the basis of repeated measures analysis (P = 0.0013). There was no statistical difference in the TSH response between these three groups. Although the PRL response was statistically different, individual PRL response patterns were not diagnostic. It appears from these data that there is an increased PRL secretion in infertile women who have histological evidence of a LPD. PMID- 3106096 TI - Evidence against the involvement of opiate neurons in mediating the effect of clomiphene citrate on gonadotropin-releasing hormone neurons. AB - This study was designed to assess whether the hypothalamic action of clomiphene citrate (CC) on gonadotropin-releasing hormone (GnRH) neurons required activity of opiate neurons. Ten women were studied in two successive cycles. In the first cycle they received infusion of saline or naloxone (2 mg intravenous bolus followed by 1.6 mg/hour) for 9 hours, in random order on days 5 and 6 of the cycle. In the second cycle each woman was treated with CC (100 mg) for 5 days before study on day 6. In each study, blood samples were collected at 15-minute intervals for 9 hours; during the last hour 10 micrograms GnRH was given to test the pituitary response. After CC, luteinizing hormone (LH) pulse frequency was accelerated, and mean serum LH, serum follicle-stimulating hormone, and estradiol increased, but the pituitary response to GnRH was unchanged. These changes are best explained by an increase in activity of GnRH neurons. Conversely, naloxone had no effect on LH pulsatility or the pituitary response to GnRH. This indicates that the action of CC at least during the early follicular phase is exerted primarily at the levels of the hypothalamic GnRH pulse generator and does not depend on the activity of opiate neurons. PMID- 3106097 TI - Evaluation of "Determine; The OvuTest" as a device for identifying optimal time for conception. AB - The device known as "Determine; The OvuTest" (Ventco Medical Trading Company, Montreal, Quebec, Canada) was appraised for its stated function of determining the optimal time for human conception by detecting the presence of the protein, uteroglobin (UTG), in cervical mucus. Twenty volunteers used the device daily through three cycles in which ovulation was indicated by rise in basal body temperature and/or elevated levels of luteinizing hormone. No correlation was found between the instrument readings and time of ovulation. When tested in vitro, it did not distinguish the presence of UTG. When vaginal flushings, containing cervical mucus, were analyzed for UTG by double immunodiffusion, no lines of precipitation were observed. We conclude that "Determine; The OvuTest" does not identify the approximate time of ovulation and therefore is not a reliable aid to conception. It does not detect UTG, and periovulation cervical mucus does not contain UTG. PMID- 3106098 TI - Ovarian hyperstimulation syndrome: prediction by number and size of preovulatory ovarian follicles. AB - Monitoring of human menopausal gonadotropin (hMG) treatment for induction of ovulation according to either preovulatory estrogen levels or the presence of a dominant ovarian follicle was found insufficient to prevent ovarian hyperstimulation syndrome (OHS). In 65 infertile patients treated with hMG and human chorionic gonadotropin (hCG), a possible correlation between the number and size of all ovarian follicles on the day of assumed ovulation and the occurrence of OHS was evaluated in order to assess the value of ultrasonography in predicting OHS. It was found that patients with OHS had significantly more follicles at the time of hCG than patients without OHS. Mild OHS was characterized by the presence of eight to nine follicles, 68.7% of which were of intermediate size (9 to 15 mm). In moderate to severe OHS 95% of the preovulatory follicles were less than 16 mm, most of them (54.7%) less than 9 mm in diameter. It can be concluded that a specific preovulatory follicular configuration characterizes mild and severe hyperstimulation. This is important information before hCG administration and emphasizes the value of ovarian ultrasonography in predicting OHS. PMID- 3106099 TI - Characteristics and incidence of dysfunctional ovulation patterns detected by ultrasound. AB - The nature and incidence of normal and abnormal spontaneous ovarian cycles, identified with ultrasound and endocrine tracking, were examined in 45 regularly cycling infertile women with no definitive cause and 15 women who were apparently normal and were receiving donor insemination because of clearly infertile partners. In 136 cycles, four apparently distinct abnormal patterns were detected. The total incidence in the infertile group was 58% compared with 23% in the donor insemination group (P less than 0.005). Twelve of 26 subjects who had at least three cycles tracked showed two different abnormalities, and 1 subject had three different abnormalities in five abnormal cycles. These results suggest that abnormal cycles are a significant factor in unexplained infertility and that diagnosis and treatment cannot be based on the study of a single cycle. PMID- 3106100 TI - Treatment-independent, treatment-associated, and pregnancies after additional therapy in a program of in vitro fertilization and embryo transfer. AB - Although the technique of in vitro fertilization and embryo transfer (IVF-ET) was developed for couples with untreatable tubal factor infertility, IVF-ET is now being applied to women with other causes of infertility and normal pelvic anatomy. In an effort to determine the treatment-independent pregnancy rate, we retrospectively reviewed the first 245 couples enrolled in the IVF-ET program at Duke University Medical Center. There were 19 treatment-independent pregnancies in 18 women and 3 treatment-associated pregnancies in cycles in which the oocyte retrieval was canceled (in 2 women washed intrauterine insemination was substituted for oocyte retrieval). Six pregnancies were established after an unsuccessful attempt at IVF-ET with additional non-IVF-ET therapy, including washed intrauterine insemination in three couples, and donor insemination in two couples. These observations suggest that a significant number of treatment independent pregnancies will occur in couples clinically deemed appropriate for IVF-ET, pregnancies can be established in cycles of controlled hyperstimulation without oocyte retrieval, and additional non-IVF-ET therapy can result in pregnancy despite failure of IVF-ET in selected couples. PMID- 3106101 TI - Ovarian stimulation by a combination of a gonadotropin-releasing hormone agonist and gonadotropins for in vitro fertilization. AB - In the first of two studies, 20 patients were selected on the basis of tubal infertility and were randomly assigned to two groups receiving different ovarian stimulation protocols. In group A, 10 patients were given follicle-stimulating hormone (FSH), FSH was continued until the criteria for human chorionic gonadotropin (hCG) administration were satisfied. In group B, 10 patients received Buserelin (0.3 ml twice a day subcutaneously) for 14 days to induce pituitary desensitization. Stimulation with FSH was then started, and Buserelin treatment was continued until hCG administration. In the second study, patients were included if they had had at least two previous attempts at ovarian stimulation that failed to reach the stage of follicular aspiration. Ovarian stimulation was conducted with a combination of Buserelin and human menopausal gonadotropin. Use of the gonadotropin-releasing hormone (GnRH) agonist in in vitro fertilization increased the number of oocytes collected, the fertilization rate, the length of the luteal phase and the pregnancy rate. The GnRH agonist also contributed to a generally better ovarian response in patients whose estradiol production had previously responded poorly to conventional ovarian stimulation protocols. PMID- 3106102 TI - Testicular involution in elderly men: comparison of histologic quantitative studies with hormone patterns. AB - An endocrinologic and quantitative histologic study was carried out in 64 elderly men who underwent orchidectomy owing to prostatic carcinoma. The men were classified into age groups (decade of life), and each group was subdivided into group A (testes with complete spermatogenesis in most tubules) and group B (testes showing maturation arrest of spermatogenesis in most tubules). Up to 80 years of age, men of group A showed hormone levels and testicular parameters similar to those of young control men. From 50 to 60 years of age, men of group B showed a significant decrease in testicular volume, tubular volume, tubular length, number of germ cells, Sertoli cells and Leydig cells per testis, and plasma testosterone levels, whereas the tunica propria thickness and plasma levels of both follicle-stimulating hormone and luteinizing hormone were increased. PMID- 3106103 TI - Reduction of fertility in the male rat by systemic treatment with follicle regulatory protein. AB - Forty-five-day-old rats received daily injections of follicle regulatory protein (FRP). After 15, 30, 45, and 70 days of therapy, serum was measured for testosterone, androstenedione, estradiol, and follicle-stimulating hormone levels. Testes were evaluated for sperm head counts, plasminogen activator activity, weight, and length of seminiferous epithelial stages. In no case was serum follicle-stimulating hormone concentration reduced in FRP-treated rats. After 75 days of treatment, there was a significant decrease in the number of the sperm head counts. After 60 days of treatment, the length of the dark zone of the tubule was longer than that of control. Pregnancy rates for FRP-treated rats were reduced after 45 and 60 days of treatment. In conclusion, systemic injection of FRP alters seminiferous epithelial function by reducing development of mature sperm. PMID- 3106104 TI - Serum levels of cholesterol and lipoproteins in rhesus monkeys: comparison of the effect of gonadotropin-releasing hormone agonist and the progestin, levonorgestrel. AB - Levonorgestrel, a progestational steroid, and the more widely used antigonadotropin, danazol have been used in the treatment of endometriosis. Both of these agents decrease serum levels of HDL cholesterol. Recently, GnRH agonists came into use for treatment of endometriosis. Our objective in this study was to compare the effects of levonorgestrel and a GnRH analog on serum cholesterol levels in rhesus monkeys being treated for surgically induced endometriosis. A high dose of levonorgestrel significantly reduced total serum cholesterol and HDL cholesterol during a 12-week treatment period. Levonorgestrel had no significant effects on the concentration of LDL/VLDL cholesterol or the percentage of total cholesterol in the HDL fraction. Conversely, the GnRH agonist had no significant effect on total serum cholesterol, HDL cholesterol, LDL/VLDL cholesterol, or the percentage of HDL cholesterol. Because the concentration of HDL cholesterol is closely correlated with atherosclerotic risk, this factor should be weighed in the overall risk/benefit analysis for the patient with endometriosis. PMID- 3106105 TI - Outcome of in vitro fertilization in women with low response to ovarian stimulation. AB - The occurrence of low-response (LR) cycles (defined as peak estradiol levels less than 300 pg/ml) in an in vitro fertilization program using a 3 ampule/day human menopausal gonadotropin regimen were retrospectively reviewed. LR occurred in 51 of 564 patients (9%). The LR serum estradiol levels were categorized into four different patterns that were further analyzed for outcome in these initial cycles, as well as for their predictive value of response in subsequent in vitro fertilization cycles. Changing the stimulation protocol to a combination of clomiphene citrate and human menopausal gonadotropin did not improve the ovarian response in this group of LR patients, and their chance to complete a subsequent normal-response treatment cycle was 32%. Suggestions are made to predict outcome and govern management of women with previous LR cycles. PMID- 3106106 TI - The outcome of continued treatment of luteinizing hormone-surged cycles in in vitro fertilization with the use of human menopausal gonadotropin. AB - Over a 2-year period 75 patients were treated for 109 cycles with human menopausal gonadotropin for in vitro fertilization. The occurrence of endogenous luteinizing hormone (LH) surges was monitored by daily blood sampling. Forty-six cycles (42%) showed an endogenous LH surge. Instead of canceling the treatment cycle as other programs do, we proceeded to oocyte collection when the surge was detected. Human chorionic gonadotropin was administered routinely to the "surge" patients as soon as the LH surge was determined. The oocyte collection was carried out around 24 hours after the "surge" blood had been drawn, although the beginning of the endogenous LH surge was unable to be pinpointed. Significantly more immature oocytes, lower fertilization rate, and lower cleavage rate were seen in the "surge" patients than in the "nonsurge" patients. In five "surge" cycles laparoscopy for oocyte collection was canceled, but none was canceled because of premature ovulation detected by the immediately preoperative ultrasonography. In four "surge" cycles no potentially fertilizable egg was recovered. This was not significantly different from that of the "nonsurge" group. The pregnancy rate of the "surge" group (4/41 or 9.8% per laparoscopy and 4/34 of 11.8% per embryo transfer) was not statistically different from that of the "nonsurge" group (7/61 or 11.5% per laparoscopy and 7/56 or 12.5% per embryo transfer). This study presents the possibility of proceeding to oocyte collection, fertilization, embryo transfer, and pregnancy in patients with endogenous LH surge in in vitro fertilization procedures with the use of human menopausal gonadotropin treatment. PMID- 3106107 TI - Results of in vitro fertilization attempts in patients with one or two ovaries. AB - The purpose of this communication is to evaluate the results of in vitro fertilization attempts in women with infertility due to a tubal factor, with one or two ovaries. Four hundred fifteen patients (788 cycles) with two ovaries and 86 patients (162 cycles) with one ovary were stimulated with gonadotropins starting on day 3 of the cycle for multiple follicular development. Although the mean number of preovulatory oocytes per laparoscopy and per transfer was significantly higher (2.33 versus 1.67 and 2.28 versus 1.99, respectively) in patients with two ovaries than in those with one ovary, the pregnancy rates per transfer were almost identical in the two groups (24.4% with two ovaries, 23.9% with one ovary). Results are presented according to different stimulation protocols and different age groups. It is concluded that although fewer fertilizable oocytes may be recruited from patients with one ovary, the potential for achieving a pregnancy is no different from that of patients with two ovaries. PMID- 3106108 TI - Comparative study of continuous and pulsed CO2 laser on tissue healing and fertility outcome in tubal anastomosis. AB - Continuous wave (CW) CO2 laser using a power of 20 W and a spot size of 0.2 mm was used to cut the left uterine horn in 15 rats. Pulsed CO2 laser using a power of 14 W, pulse repetition rate of 400 pps, and a spot size of 0.2 mm was used to cut the left uterine horn in 16 rats. The right uterine horn was sham-operated and used as a control in each group. Microsurgical anastomosis of the cut horn was performed. The effect on fertility showed a pregnancy rate of 66.6% and 81.25% for the CW and pulsed CO2 laser, respectively. Histopathology studies of the anastomotic site revealed thinning of muscularis with fibrosis of both muscularis and subserosal layers in the CW CO2 laser-treated group. There was no thinning, disruption, or fibrosis of muscularis in pulsed laser-treated group. Adhesion score was not different in the two groups. PMID- 3106109 TI - Cost-effectiveness of a monitor technician program: an analysis. PMID- 3106110 TI - [Modules--functional units of the visual brain--and their role in visual perception]. PMID- 3106111 TI - [The selectivity factor in the organization of the complex behavior of the monkey]. PMID- 3106112 TI - Vitamin K-dependent carboxylation. PMID- 3106114 TI - Purification and characterization of camel liver glutathione S-transferase. AB - Glutathione S-transferases have been purified (18-fold) in 65-70% yield from the liver of one humped camel using affinity chromatography on glutathione-linked agarose. Chromatofocusing technique resolves the glutathione S-transferases into seven distinct isoenzymes with apparent pI of 8.7, 8.4, 8.0, 7.8, 7.3 and 6.5. The major isoenzyme (pI 8.7) which accounted for over 95% of the total activity was composed of two identical subunits of molecular mass 24,000 and was immunologically similar to the other six isoenzymes. The substrate specificities and the effect of various inhibitors on the activity of the abundant camel liver isoenzyme were also examined. PMID- 3106113 TI - The inactivation of beta-galactosidase (E. coli) by the carbodiimide reaction. AB - When beta-galactosidase reacted with 1-ethyl-3(3-dimethylaminopropyl) carbodiimide (EDC), activity was lost. The inhibitor, isopropyl-beta-D galactopyranoside (IPTG), decreased inactivation. Of 3 nucleophiles tested, incorporation was only decreased in the protected (IPTG added) enzyme when sulfanilic acid was the nucleophile but HPLC profiles of tryptic peptides were identical in protected and unprotected enzyme (except for magnitude). There were also no differences (except for magnitude) of HPLC profiles after 10 and 90 min of reaction and between active (soluble) and inactive (precipitated) enzyme. The data indicate that inactivation is not caused by reaction with a specific active site group. Inactivation probably occurs when a combination of groups are reacted. PMID- 3106115 TI - Carbonic anhydrases. AB - Some of the current studies of carbonic anhydrases are directed to the genetic mechanisms underlying their synthesis. Determination of the structure of their genes will probably most readily resolve the question of whether the membrane bound forms of the enzyme represent products of additional loci other than those of the three well-known soluble forms. Extensions of our knowledge of the sequences of these isozymes as well as those from lower animals and from plants will make possible a more precise evaluation of the extent of the multigene aspects of these proteins and their evolutionary backgrounds. Studies of the interrelationships of the regulation of the transcriptional and translational processes of the well-known isozymes and in particular the effects of hormones will be of interest. Insights into modifications of the isozymes' synthetic processes occurring in various diseases should also be forth-coming from these studies. In addition to the above the applications of what are perhaps today somewhat classical methods of protein chemistry will be needed to explore the reasons for the changes in activity accompanying the sequence variations of the different isozymes, the decreases or increases in activity accompanying derivatizations of specific residues and the reasons for the differences in the activity of different inhibitors on the various isozymes. The broad specificity of these enzymes for different substrates and the ability of CA-III to hydrolyze various phenyl esters and in some cases to become derivatized also present problems in protein structural chemistry. In terms of the latter reactions, the meaning of the relationships of these activities to those of the protein ubiquitin, which is homologous to CA-III, needs clarification. It would appear that various of the protein structural studies will be aided by crystallographic investigations of not only CA-III but of various of its derivatives which undergo either increases or decreases in activity. The above areas of studies present a wide variety of problems for workers in various disciplines and backgrounds who are interested in the carbonic anhydrases. PMID- 3106116 TI - Effect of phosphatidyl-L-serine and vinculin on actin polymerization. AB - The effects of phosphatidyl-L-serine (PS) and/or vinculin on actin polymerization are examined by spectrophotometry, viscometry and electrophoresis. Actin polymerization is inhibited by PS alone and stimulated by PS and vinculin. The results suggest that actin does not directly adhere to cell membrane and that vinculin is a protein which is involved in structures connecting actin microfilaments to cell membranes. PMID- 3106117 TI - Biphasic effect of thyrotropin-releasing factor (TRH) on alpha-melanotropin secretion from frog intermediate lobe in vitro. AB - The kinetics of alpha-MSH secretion induced by prolonged TRH infusion were studied using perfused frog neurointermediate lobe (NIL). During a 2 h administration of TRH (10(-8) M), the secretion rate of alpha-MSH displayed two phases. During the first phase, secretion of alpha-MSH increased rapidly reaching a maximum within 20 min and then, despite continued TRH infusion, this secretion slowly declined. The second phase was characterized as plateau of elevated release (relative to basal secretion); within this second phase there was often a small peak of released alpha-MSH occurring at about 100 min. Exposure of NIL to another TRH (10(-8) M) pulse 90 min later induced a normal stimulation of alpha MSH secretion, thus demonstrating the viability of tissue in perifusion. Continuous infusion of cycloheximide (10(-5) M) during a 5 h period totally inhibited the biosynthetic activity of NIL but did not influence TRH-induced alpha-MSH secretion. In particular, cycloheximide had no effect on the second phase of the response to prolonged infusion of TRH. Similarly, during continuous infusion of the monovalent carboxylic ionophore monensin (10(-6) M), the biphasic response to prolonged infusion of TRH (10(-8) M) was still observed. Administration of a short pulse of TRH (10(-7) M) during the declining part of the first phase or during the second phase of prolonged TRH (10(-8) M) infusion induced a significant enhancement of alpha-MSH stimulation. From these results we conclude that prolonged TRH infusion causes alpha-MSH release in a biphasic manner; attenuation of the secretory response to continuous TRH administration does not result from exhaustion of the releasable pool of alpha-MSH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106118 TI - Human chorionic gonadotropin stimulation of immunoreactive prostaglandin synthase in the rat ovary. AB - Follicular prostaglandins (PG) increase markedly in the hours after the preovulatory gonadotropin rise in the rat. The present investigation was performed to determine if the increased prostaglandins result from elevation of the amount of the principal enzyme in the conversion of arachidonic acid to prostaglandins, i.e. PG synthase. PG synthase was purified from sheep seminal vesicles and rat ovaries for the preparation of monoclonal antibodies. A monoclonal antibody was utilized in a competitive, microtiter plate-based enzyme immunoassay to quantitate PG synthase protein. Follicular development was stimulated in 26-day-old rats by injection of 20 IU of PMSG, and 51 h later 20 IU of hCG was injected. Ovaries were removed from rats before and 8 h after the hCG injection for quantitation of PG synthase by enzyme immunoassay. PG synthase immunologic activity was increased three-fold by hCG stimulation. These findings support the hypothesis that the preovulatory gonadotropin rise causes increased PG synthase protein in the rat ovary. PMID- 3106119 TI - The indirect flight muscle of Drosophila accumulates a unique myosin alkali light chain isoform. AB - Mapping of the 5' and 3' ends of the Drosophila myosin alkali light chain (MLC ALK) mRNA by S1 nuclease and primer extension assays has shown that the primary transcripts are identical irrespective of the time in development that the RNA was prepared. As shown by S1 nuclease experiments these transcripts are alternatively spliced in a tissue-specific fashion generating mRNAs that encode tissue-specific protein isoforms. Antibodies were raised to synthetic peptides identical in sequence to the unique portion of each protein. Western blots of one dimensional polyacrylamide gels using the type-specific antibodies confirmed and extended the results obtained from the S1 nuclease experiments. The indirect flight muscle is the only tissue in the adult that accumulates the alternatively spliced mRNA. The choice between splicing pathways involves the use of a nonconsensus 3' splice junction in larvae and in the tubular muscles of adults, whereas in the indirect flight muscle of the adult only consensus sequences are utilized. The involvement of a trans-acting factor to activate the nonconsensus splice site in the myotubes of larvae and the tubular myotubes of adults is proposed. PMID- 3106120 TI - Translation of maternal histone mRNAs in sea urchin embryos: a test of control by 5' cap methylation. AB - Recent results have demonstrated the occurrence of mRNA cap methylation in the sea urchin embryo following fertilization. It has been suggested that this methylation event is responsible for the translational activation of maternal histone mRNAs in these embryos. We have used aphidicolin, an effective inhibitor of both DNA synthesis and cap methylation in cleavage stage sea urchin embryos, to examine the relationship between cap methylation and translation. At 5 micrograms/ml, a dose which rapidly abolishes DNA replication and blocks cleavage, we note no effect on recruitment or translation of maternal alpha subtype histone mRNAs. This suggests that a postfertilization cap methylation event is not critical to the process of regulation of the translation of stored alpha-subtype histone mRNAs. PMID- 3106121 TI - Changes in the phosphorylation and distribution of vinculin during nerve growth factor induced neurite outgrowth. AB - The mechanism of neurite initiation and elongation was studied using nerve growth factor (NGF) treatment of PC12 cells. The distribution of focal adhesion sites and of the cytoskeletal protein vinculin was determined in large, fused, multinucleated PC12 cells. In the absence of NGF, focal adhesion sites as seen by interference reflection microscopy were restricted to the cell periphery in a regular distribution. Vinculin assemblies (foci), observed by indirect immunofluorescence microscopy using affinity purified anti-vinculin antibodies, were restricted to the cell periphery at focal adhesion sites. Within 4 hr after NGF treatment of the cells, the distribution of both vinculin and focal adhesion sites began to change. Focal adhesion sites became restricted to discrete protruding portions of the cell periphery. Larger, brighter vinculin foci appeared at the tips of the cell margin extensions, concomitant with the loss of foci at locations between the protrusions. As neurites elongated focal adhesion sites and vinculin foci remained with the tips of the growth cone extensions. Both focal adhesion sites and vinculin foci were rarely seen in the perikarya of cells with elongating neurites, and these were always confined to extended portions of the cell body margin. Occasionally, vinculin foci could be seen at the proximal portion of the neurite, at bending elbows, and at discrete expansions along the length. By immunoprecipitation of vinculin from 32P-labeled cells, vinculin phosphorylation was found to be increased within 1 hr of NGF treatment. The role of vinculin phosphorylation and assembly in the formation and directional elongation of neuritic processes in response to NGF is discussed. PMID- 3106122 TI - Sulfonylurea-induced inhibition of glucagon secretion from the perfused rat pancreas: evidence for a direct, non-paracrine effect. AB - The effects of sulfonylurea on glucagon secretion were characterized in the perfused rat pancreas using glibenclamide (1 microgram/ml) or tolazamide (10 micrograms/ml) in the presence of 3.3 mmol/l glucose. Glucagon release, which was unaffected by glibenclamide at 2.75 mmol/l calcium, was suppressed at 1.19 and 0.64 mmol/l but transiently stimulated at 0.25 mmol/l extracellular calcium. The insulinogenic effect of glibenclamide at 0.64 and 0.25 mmol/l calcium was enhanced by 35% and 89%, respectively, compared to the response at 2.75 mmol/l calcium. The stimulatory effect of the compound on somatostatin secretion, however, was lost at the lower calcium levels. The effects of tolazamide at 2.75 and 0.64 mmol/l calcium mimicked those of glibenclamide, thus indicating that our results with the latter compound may be representative for all sulfonylureas. In pancreata from insulin-deficient alloxan-diabetic rats, glibenclamide completely lost its inhibitory effect on glucagon release at 0.64 mmol/l calcium. Inhibition was not restored by adding insulin (25 U/l) to the perfusate. However, when diabetic rats had been treated with insulin for 6-7 days, glibenclamide suppressed glucagon release at low calcium levels in the absence of stimulated insulin and somatostatin release. It is concluded that, at low calcium concentrations, sulfonylureas suppress glucagon secretion by a direct action on the A cell and not through paracrine interactions by insulin and somatostatin. Prolonged insulin deficiency impairs the sulfonylurea action on glucagon secretion. PMID- 3106123 TI - Effect of growth hormone releasing hormone on growth hormone secretion in type 2 (non-insulin-dependent) diabetes mellitus. AB - Growth hormone levels following an intravenous bolus injection of 1 micrograms/kg body weight growth hormone releasing hormone were measured in 21 non-obese and 26 obese patients with Type 2 (non-insulin-dependent) diabetes mellitus and in 13 control subjects. Growth hormone responses in non-obese Type 2 diabetic patients were not statistically different from control subjects. However, obese Type 2 diabetic patients had significantly decreased growth hormone responses to growth hormone releasing hormone when compared with non-obese Type 2 diabetic patients (p less than 0.02). In 9 Type 2 diabetic patients growth hormone releasing hormone tests were performed both during hyperglycaemia and after metabolic improvement by insulin treatment. Growth hormone responses before and after insulin treatment were not statistically different. Our data demonstrate that growth hormone responses to growth hormone releasing hormone in non-obese Type 2 diabetic patients do not differ significantly from control subjects; obesity blunts growth hormone responses to growth hormone releasing hormone in Type 2 diabetes mellitus; and growth hormone responses following growth hormone releasing hormone administration in Type 2 diabetes mellitus are not influenced by the state of metabolic control. PMID- 3106124 TI - Prolongation of graft survival in allogeneic islet transplantation by (-) 15 deoxyspergualin in the rat. AB - The effect of 15-Deoxyspergualin, a novel drug which has been described to have anti-tumour activity, on allogeneic graft survival (Dark Agouti----Lewis rats) after pancreatic islet transplantation was tested. A marked prolongation of graft survival could be shown using doses of 1.0, 2.5 and 5.0 mg Deoxyspergualin/kg on day 0 until day +9 post transplantation. A maximum of 55.6 days (average) survival time was observed using 2.5 mg/kg Deoxyspergualin compared to 5.2 +/- 0.6 days without immunosuppression. Using the chemiluminescence reaction of recipient monocytes after islet transplantation, a marked suppression of the monocyte system exceeding the treatment period could be observed. Since, in contrast to cyclosporin, B-cell toxicity could not be shown, the new drug seems to be a hopeful step towards successful allogeneic islet transplantation for treatment of diabetes. PMID- 3106125 TI - Prolongation of rat pancreatic islet allograft survival by treatment of recipient rats with monoclonal anti-interleukin-2 receptor antibody and cyclosporin. AB - Since interleukin-2-receptor expressing cells play a role in allograft rejection, we investigated the effect of anti-interleukin-2 receptor monoclonal antibody treatment on graft survival of allografted pancreatic islets. When pancreatic islets obtained from Lewis A-rats (haplotype RT1a) were grafted under the kidney capsules of streptozotocin-diabetic Lewis rats (haplotype RT1u), the recipients relapsed into hyperglycaemia within 11 days (7 +/- 1 days). Treatment of the recipient rats with low-dose cyclosporin (1.5 mg/kg body weight) had no effect on allograft survival (9 +/- 1 days). The application of anti-interleukin-2 receptor monoclonal antibody (1 mg/kg body weight) for 10 days resulted in a prolongation of allograft survival (42.5 +/- 15.3, p less than 0.01). In 3 out of 11 animals a permanent normoglycaemia (greater than 120 days) associated with glucose intolerance was observed. When the recipients were treated for 10 days with cyclosporin and anti-interleukin-2 receptor monoclonal antibody, the allograft survival was also prolonged (45.1 +/- 14.6, p less than 0.01); again 3 out of 11 animals remained permanently normoglycaemic while exhibiting a normal glucose tolerance. PMID- 3106127 TI - [Evaluation of the use of parenteral nutrition in chronic and severe radiation enterocolitis]. AB - The effects of parenteral nutrition in the treatment of patients with severe chronic radiation enterocolitis is not known. We retrospectively studied 19 adult patients who received parenteral nutrition during 8.6 +/- 2.4 months (mean +/- SEM), including 6 cases in our home-parenteral nutrition-program. Parenteral nutrition was started 49 +/- 12 months after radiation therapy; follow-up after parenteral nutrition was 22 +/- 7 months. Indication for parenteral nutrition was malnutrition (weight = 73 +/- 2 p. 100 of ideal body weight, serum albumin level = 27 +/- 1 g/l) due to multifocal gastrointestinal radiation injuries with stenoses (n = 12), fistulae (n = 3) and short bowel syndrome (n = 4). Parenteral nutrition was given during the peri-operative period in 15 patients. Neither fistulae nor stenoses resolved with parenteral nutrition alone (n = 7) or in association with steroids (n = 5). There was a 57 p. 100 mortality rate (11 patients): 10 p. 100 were postoperative (2 of the 3 patients with fistulae), 21 p. 100, due to radiation complications and 26 p. 100, due to progression of cancer. In those patients with severe and multifocal chronic radiation enteropathy, parenteral nutrition did not influence the lesions in the digestive tract. Nutritional support could, however, be considered as an useful adjunct with a low perioperative mortality rate. In the 14 patients without superimposed unresponsive cancer, parenteral nutrition followed by curative abdominal surgery seemed to be associated with the best prognosis and in 7 of the 8 survivors, parenteral nutrition has been discontinued without reappearance of clinical malnutrition. PMID- 3106126 TI - Impact of metabolic control in progression of clinical diabetic nephropathy. AB - Renal clearance of 51Cr-EDTA as a measure of glomerular filtration rate was followed prospectively for 21 months in 18 Type 1 (insulin-dependent) patients with juvenile-onset diabetes and nephropathy. Hypertension was treated aggressively, attaining a mean blood pressure of 154/88 mmHg in the supine and 126/82 mmHg in the standing position. The mean glycosylated haemoglobin value (HbA1c) during the observation period was found to correlate well with the mean of random blood glucose values (r = 0.72). It also correlated to the rate of glomerular filtration rate decline over time, whether the latter was calculated as slope coefficient for all available data (r = -0.52, p less than 0.05) or based on the first and last observations only (r = -0.57, p less than 0.05). In a multiple linear stepwise regression analysis also including mean arterial blood pressure, the correlation between glomerular filtration rate decline and HbA1c was significant at p less than 0.01; this explained one-third of the progression, while mean arterial pressure could not be shown to contribute. It is concluded that hyperglycaemia, contrary to the general belief, is a risk factor for the progression of clinical diabetic nephropathy with reduced glomerular filtration rate. PMID- 3106128 TI - Paradoxical effects of gastrin releasing peptide on gastrin release and gastric secretion in the rat. AB - The effects of gastrin releasing peptide (GRP) on gastrin release and gastric secretion were studied in anesthetized rats. Intravenous infusion of GRP (1-16 micrograms/kg/hr) caused a dose-dependent increase in serum gastrin level, however, it had no effect on basal gastric secretion in the lumen-perfused stomach preparation. Furthermore, GRP inhibited gastric secretion stimulated by pentagastrin or histamine dose-dependently, but not by carbachol. Simultaneous infusion of GRP and a beta adrenergic blocking agent, propranolol, an inhibitor of somatostatin release, did not alter the inhibitory effect of GRP on pentagastrin-stimulated gastric secretion. These results suggest that the inhibitory effect of GRP on gastric secretion in a stimulated condition is mediated via peptide hormones coreleased by GRP, and not via beta-adrenergic pathways. PMID- 3106130 TI - Histogenesis of malignant histiocytosis of the intestine. PMID- 3106129 TI - Human mucosal cytotoxic effector cells. AB - Human intestinal lamina propria mononuclear cells have been shown to mediate mitogen-induced cellular cytotoxicity, antibody-dependent cellular cytotoxicity, and lymphokine activated killer cell function. However, although natural killer cells have been demonstrated in the gut mucosa of rodents, recent reports found little or no spontaneous cytotoxic activity in the lamina propria of the human gut. Using the natural killer cell-related monoclonal antibody NKH-1, which has not previously been applied to studies of mucosal killer cell function, we have shown by immunofluorescence that 2%-3% of enzymatically dispersed lamina propria lymphocytes are NKH-1+. A "panning" technique was then used to enrich for the NKH 1+ cells. Panned cells were consistently greater than or equal to 80% NKH-1+ by indirect immunofluorescence. Unlike their counterparts in the peripheral blood, the mucosal NKH-1+ cells were Leu-11-. Although unseparated lamina propria lymphocytes failed to exhibit natural killer activity against K562 targets in 4-h chromium release assays at effector to target ratios of up to 100:1, the NKH-1+ cells were cytolytically active at ratios of less than 5:1. Mucosal lymphocytes depleted of natural killer cells (NKH-1-) exhibited cytotoxic activity when cultured for 72 h with interleukin-2. The precursors of the lymphokine culture activated phenomenon were NKH-1-, Leu-11-, T4-, T3-, T11+, and T8+. Although lamina propria T3+ cells did not exhibit spontaneous or culture activated cytotoxicity, they were shown to exhibit nonspecific anti-CD3 (anti-T3)-induced T cell cytotoxicity. In conclusion, functional natural killer and lymphokine activated killer cells are both present in the human gut mucosa and represent distinct populations of cytotoxic cells. In addition, anti-CD3-induced cytotoxicity is a feature of mucosal T cells. These mucosal killer cell subsets differ phenotypically from those previously described in the peripheral blood. PMID- 3106131 TI - Endoscopic placement of nasoenteral feeding tubes. PMID- 3106132 TI - [Treatment of urinary tract infections with SolcoUrovac]. AB - Urinary tract infections are among the most common infections found in women. If recurrences or reinfections become frequent treatment can be problematic. Immunisation of the patients by vaccinating them against urinary tract pathogens offers a possibility of managing these infections. In clinical trials we tested SolcoUrovac, a new vaccine to counteract bacterial pathogens, with regard to efficacy, frequency of recurrence, and tolerance. 113 of the 118 patients included in this study with bacteriuria (urine culture germ count greater than or equal to 10(5)/ml), had acute cystitis. 47 of these patients had recurring urinary tract infections. Follow-up examinations were conducted after 2, 3, 4, 5, 6 and 12 months. A urine culture assay was performed during each examination, as well as a relevant bacterial differentiation test and a urine sediment evaluation. Two to six weeks after termination of the vaccination series 72.6% of the patients were largely free from signs and symptoms. The rate of recurrence/reinfection dropped from 2.5 to 0.24 infections for a period of 12 months. After one year, 94 of the patients (80%) were still free from reinfection. PMID- 3106133 TI - [Approach to a new compensatory management of the hypotrophic fetus]. AB - This is a report on a new possibility of effecting direct compensatory supply of vitally essential substances on the hypotrophic foetus. Supply of amino acids and other important substances is effected via an indwelling catheter introduced into the abdominal cavity of the foetus. To avoid infections it is advisable to provide for sufficiently long tunnelling of the mother's skin and to implant an application capsule into the abdominal wall of the mother in such a manner that the system is in no way openly connected to the outside, treatment being effected transcutaneously through the mother's skin. It is well known from peritoneal dialyses that the peritoneum is highly permeable especially for low molecular substances. A report is given on a case where the system could however be applied for 9 days only because of premature rupture of the foetal membranes and subsequent birth of a viable child. During the intraperitoneal supply of the foetus it was possible to show by instillation of 13C leucine (effected in cooperation with paediatricians) that the foetus had taken up the supplied amino acids and had metabolised and excreted these via the placenta and finally the mother's expiratory air to a slight extent only; the major part had, therefore, been utilised for anabolism. The article discusses potential risks that can be envisaged at the present moment, such as intestinal injuries during puncture, infections and premature rupture of the membranes. PMID- 3106134 TI - The search for ideal antidote treatment in Gramoxone intoxication. AB - The herbicide Gramoxone (the active ingredient is paraquat) actively accumulates in the lung in the mammalian organism, where it exerts its toxic effect through the generation of oxygen radicals. Efforts were made to counteract the toxic effect in experiments in mice. Its penetration into the cells was blocked with the diamines putrescine and cadaverine. The synthesis of the prostaglandins, which are supposed by responsible for the acute symptoms, was inhibited with Aspisol. Accumulation inhibition with biogenic amines is considered the most effective. PMID- 3106135 TI - Effect of selective monoamine oxidase inhibitors on the morphine-induced hypothermia in restrained rats. AB - Morphine (30 mg/kg i.p.) produced a hypothermic effect in restrained rats which was antagonized by naloxone pretreatment (10 mg/kg s.c.). This hypothermia was inhibited by deprenyl pretreatment (5 mg/kg i.p.) and by beta-phenylethylamine treatment (25 mg/kg i.p.). However, the effect of morphine was partially potentiated when a higher dose of deprenyl (10 mg/kg i.p.) was administered. Pretreatment with clorgyline (1 mg/kg i.p.) potentiated the morphine-induced hypothermia. In contrast, the effect of morphine was antagonized when a higher dose of clorgyline was used (5 mg/kg i.p.). Based on these results, a possible role of brain serotonin and dopamine in the thermoregulatory effects of morphine is proposed in this paper. PMID- 3106136 TI - Effects of a new anorectic drug (PM 170) on development of gold thioglucose induced obesity in mice. AB - Gold thioglucose (GTG)-injected mice and lean mice were treated for 16 days with PM 170. The body weight and body fat were significantly increased by GTG injection and these increases in the GTG-obese group were reduced by PM 170. PM 170 also reduced food intake (16%), total body triacylglycerol (51%) and total body cholesterol (36%). Basal lipolysis of white adipose tissue, as measured by glycerol release, was stimulated by 150%. Compared to GTG-PM 170 mice, body weight gain was 2 times higher in GTG-pair-fed mice. Body fat and total body lipid content remained elevated. PMID- 3106137 TI - Peptides with antilipolytic and lipogenic activities from seeds of the bitter gourd Momordica charantia (family Cucurbitaceae). AB - Decorticated Momordica charantia seeds were extracted with acidic ethanol. The pH of the extract was adjusted to 8 and the resulting precipitate was chromatographed on CM Sepharose CL-6B and then desalted on Sephadex G-10. A number of factors which exhibited antilipolytic and lipogenic activities in rat adipocytes were isolated. Two of the factors were demonstrated to be peptides with similar amino acid compositions and a molecular weight of approximately 8000. However the peptides greatly differed in their chromatographic behavior on CM-Sepharose CL-6B and in their mobilities in agarose and polyacrylamide gel electrophoresis. PMID- 3106138 TI - Ovine ureteral motility as a new assay for the cyclo-oxygenase blocking potency of non steroidal anti-inflammatory drugs. AB - Isolated sheep ureteral ring suspended in an organ bath exhibits rhythmic contractions which are dose-dependently inhibited by indomethacin and revived by prostaglandin E2 or F2 alpha. Seven non-steroidal anti-inflammatory drugs (NSAID) belonging to different chemical groups were tested on the isolated ureteral ring model in molar concentrations of 10(-8)-10(-4) to determine the time elapsing from application of test drug to complete inhibition of ureteral contraction ("stop-time"). The descending order of potency of the NSAID was: flurbiprofen greater than indomethacin greater than flufenamic acid greater than tolmetin greater than aspirin greater than phenylbutazone greater than isoxicam. A parallelism was observed in the plot of log concentration of NSAID and "stop time" amongst all compounds except aspirin and isoxicam. The sheep isolated ring preparation is a simple reproducible biological model for assessment of anti inflammatory cyclo-oxygenase inhibitory activity of compounds. PMID- 3106139 TI - [Non-surgical management of obstructive jaundice]. PMID- 3106140 TI - [Echography of abdominal abscesses]. PMID- 3106142 TI - [Hemorrhoids and portal hypertension]. PMID- 3106141 TI - [Endoscopic sclerosis of esophageal varices in children]. PMID- 3106144 TI - [Liver transplantation. Possibilities in Venezuela]. PMID- 3106143 TI - [Effects of YAG-laser on the mucosa of the upper digestive tract. In vitro study]. PMID- 3106145 TI - [Precocious and advanced malignant gastric neoplasm. Endoscopic analysis and pathological correlation]. PMID- 3106146 TI - [Hemobilia review apropos of a case]. PMID- 3106148 TI - Behavioral and cytogenetic analysis of the cacophony courtship song mutant and interacting genetic variants in Drosophila melanogaster. AB - The courtship song of a Drosophila melanogaster male consists of tone pulses interspersed with humming sounds. An X chromosomal mutation, cacophony (cac), causes the production of polycyclic pulses readily distinguishable from those in wild type, which are mono- or bicyclic. Yet, courtship hums and flight wing beats are normal in this mutant, suggesting a specific role of the cac gene in the neural program underlying one particular feature of the fly's wing vibrations. A precise cytogenetic localization of cac is presented; this was obtained by uncovering the song abnormality with deletions that are missing all or the distal part of region 11A; the flies tested were diplo-X adults that had been turned into males by the transformer mutation. Duplications including distal 11A covered cac. The possibility of behavioral specificity for cac's effects was examined by screening a variety of sexual and nonsexual behaviors; these experiments included tests of flies in which the mutation was uncovered by a small deletion. We conclude that cac causes only a limited array of well-defined defects: longer and louder tone pulses in the song and depressed locomotor activity. Further complementation tests involving cac and other closely linked genetic variants- the night-blind-A (nbA) visual mutation, l(1)L13 lethal mutations, and a series of X chromosomal breakpoints--suggested complex interactions among these factors: the breakpoints uncover all three types of mutations; cac and nbA appear to be alleles of l(1)L13, whereas the two behavioral mutations complement each other. PMID- 3106147 TI - [Primo-infection histoplasmosis with esophageal localization (1st case reported in Venezuela)]. PMID- 3106150 TI - [Construction of plasmids integrating into the Bacillus subtilis chromosome through homologous recombination and their use as integration vectors]. AB - We constructed a number of plasmids which integrate into the chromosome of Bacillus subtilis through homology recombination. Plasmids consist of pBR322 replicon, different fragments of Bac. subtilis chromosomal DNA, Cm resistance marker from pBD64 plasmid. Frequency of transformation was 10(-4) per bacterial cell. Foreign DNA (genes for tryptophan metabolism of Bac. mesentericus) was introduced into the chromosome of Bac. subtilis with the help of these plasmids. PMID- 3106149 TI - DdcDE1, a mutant differentially affecting both stage and tissue specific expression of dopa decarboxylase in Drosophila. AB - The isolation and characterization of a unique Dopa decarboxylase (Ddc) mutant in Drosophila melanogaster is reported. This mutant, DdcDE1, exhibits stage- and tissue-specific altered Ddc expression. Homozygous DdcDE1 embryos, central nervous systems (CNSs) at pupariation and newly eclosed adult epidermis all have approximately 5% as much specific dopa decarboxylase (DDC) activity as the pr control stock in which DdcDE1 was induced. In contrast, the DdcDE1 epidermis at pupariation has roughly 50% as much DDC activity as controls, a 10-fold increase over the relative activity detected in other tissues and stages. Although the adult cuticle lacks proper pigmentation as expected in flies with low DDC activity (less than or equal to 5%), the bristles unexpectedly have wild-type black pigmentation. This implies that the bristle forming cells have more DDC activity than the rest of the adult epidermis. This variegated phenotype, black bristles and pale cuticle, plus the fact that DdcDE1 was originally isolated in a reciprocal translocation between proximal X heterochromatin and the euchromatic left arm of the second chromosome, 42 bands from the Ddc locus, suggested that the mutant might be an example of position-effect variegation. All tests for position-effect variegation, including persistence of the mutant phenotype when DdcDE1 was removed from the translocation, were negative. At pupariation DDC cross-reacting material (CRM) levels are similar in DdcDE1 and wild-type controls, but in newly eclosed adults CRM levels are approximately 35% of wild type controls. This suggests that DDC produced by DdcDE1 adults has less activity per DDC molecule than the DDC produced at pupariation by DdcDE1. If the DDC enzyme produced by DdcDE1 at adult eclosion had full DDC activity (35% DDC CRM = 35% DDC activity) then no mutant phenotype would be exhibited by DdcDE1 since flies with as little as 10% activity have a wild-type phenotype. DDC thermolability assays clearly demonstrate that DDC from DdcDE1 is more thermolabile than control DDC at both pupariation and adult eclosion. Furthermore, DDC from adults in both DdcDE1 and the pr control is more thermolabile than DDC from white prepupae. Mixing experiments indicate the difference in DDC thermolability between pr white prepupae and pr adults is not due to a difference in the white prepupal and adult supernatants. This suggests that in wild-type different isoforms of DDC are produced either by differences in post-translational modification or as a result of a different primary amino acid sequence.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3106151 TI - A chromosomal segment conserved since divergence of lineages leading to man and mouse: the gene order of aminoacylase-1, transferrin, and beta-galactosidase on mouse chromosome 9. PMID- 3106152 TI - The primary structure of cynomolgus monkey apolipoprotein A-1 deduced from the cDNA sequence: comparison to the human sequence. AB - We have cloned and analyzed a cDNA containing the complete coding sequence for cynomolgus monkey apolipoprotein A-1 (apoA-1). This cDNA clone was found to share approx. 97% nucleotide sequence identity with the published human apoA-1 and encodes a protein of the same size as the human protein. Paired proline residues are present at positions 3 and 4 in the mature protein as has been reported for other primate species and the propeptide sequence is identical to the human propeptide. The amino acid content derived from the nucleotide sequence predicts a more basic protein than human apoA-1 and this was confirmed by isoelectric focusing analysis. In addition, we present evidence for two different transcriptional initiation sites for the cynomolgus monkey gene in contrast to only one for human. PMID- 3106153 TI - The organization and nucleotide sequence of the Bacillus subtilis hisH, tyrA and aroE genes. AB - The nucleotide sequence of approximately 3 kb of Bacillus subtilis DNA distal to the trp operon was determined. Three open reading frames were found and these were shown to encode the hisH, tyrA and aroE genes. Integrative plasmids were constructed to interrupt transcription through this region. These data suggest that these three genes can be transcribed from both the trp promoter preceding the trp operon and from a promoter within the trpA structural gene. PMID- 3106154 TI - Fusion of pro region of subtilisin to staphylococcal protein A and its secretion by Bacillus subtilis. AB - Subtilisin is synthesized as a preproenzyme in Bacillus subtilis. We fused that region of the subtilisin gene, (apr[BamP]), which encodes the signal sequence and pro region, to the mature gene sequence (spa) for a heterologous protein (staphylococcal protein A). B. subtilis cells harboring this gene fusion synthesized a fusion protein consisting of the signal and pro sequence of subtilisin fused to the protein A; the signal sequence was processed and a fusion protein (pro + protein A) was secreted into the growth medium. PMID- 3106155 TI - Sequence analysis of the Bacillus subtilis argC promoter region. AB - A previously characterised promoter region upstream from the Bacillus subtilis argC gene was sequenced. The in vivo position of transcription start point (+1), was determined by mung-bean-nuclease mapping. The nucleotide (nt) sequences in the '-10' (TATAAT) and '-35' (TTGAAT) regions closely resemble consensus promoter sequences recognised by B. subtilis sigma 43 and Escherichia coli sigma 70 RNA polymerases. Between +9 and -64 are three imperfect inverted repeats with high homology to the E. coli arginine biosynthetic gene putative operator sequences (ARG boxes) [Cunin et al., Nucl. Acids Res. II (1985) 5007-5019] and which contain variable intra-repeat distances. Upstream from the '-35' region, extending as far as -71, is a 97% AT-rich sequence. The argC mRNA has a short leader region containing a B. subtilis ribosome-binding site 8 nt upstream from a TTG start codon for an open reading frame (ORF). The deduced amino acid sequence for this ORF contains regions of homology to that for the E. coli argC N-terminal region. PMID- 3106156 TI - Expression in Escherichia coli of synthetic human interleukin-1 alpha genes encoding the processed active protein, mutant proteins, and beta-galactosidase fusion proteins. AB - We have synthesized, cloned, and expressed the coding region for the C-terminal 159 amino acids (aa) of the human active interleukin polypeptide hormone IL-1 alpha. The sequence was assembled in stages and includes preferred Escherichia coli codons and unique restriction sites. The coding region was cloned on a multicopy plasmid vector adjacent to signals for transcription and translation that directed synthesis of 6% of total E. coli protein as IL-1 alpha. Active IL-1 alpha mutants that have a C-terminal additional eleven aa and that have N terminal deletions of six and fourteen aa are described. Plasmids expressing beta galactosidase fusion proteins with various parts of IL-1 alpha at their N-termini were constructed. PMID- 3106157 TI - The human transferrin gene: 5' region contains conserved sequences which match the control elements regulated by heavy metals, glucocorticoids and acute phase reaction. AB - Transferrin is a major plasma protein that transports iron to proliferating cells throughout the body. A clone containing the 5' region of the human transferrin gene has been isolated and characterized. A 14 kb EcoRI fragment was identified that contained the first 8 exons of the transferrin gene and 3.6 kb of its 5' flanking region. Conserved sequences identical or homologous to regulatory elements responding to heavy metals, glucocorticoid receptor and a putative acute phase reaction signal were identified in the 5'flanking region and intron 1. Also, the regulatory region of the transferrin gene contains a 14-bp sequence which closely matches sequences found in the interleukin-2 and gamma-interferon genes. All three genes are expressed by T lymphocytes before proliferation. A secondary loop structure similar to that proposed for the ovotransferrin gene can be formed by sequences in the 5' untranslated region of the transferrin mRNA. PMID- 3106158 TI - The beta-glucanase gene from Bacillus amyloliquefaciens shows extensive homology with that of Bacillus subtilis. AB - The nucleotide sequence of a 1583-bp DNA fragment containing gene bg1A for endo beta-1,3-1,4-glucanase (EC 3.2.1.73) of Bacillus amyloliquefaciens strain BE20/78, a high producer of secreted enzymes, has been determined. The gene bg1A comprises an open reading frame (ORF) of 717 bp (= 239 codons) starting with ATG at 469 up to the translation stop codon TAA at 1188. Upstream from the translation initiation codon ATG, the ribosome-binding sequence 5'-AAAAAAGGGGG-3' and two putative bglA promoters have been identified. A box of eleven AT out of twelve base pairs (bp) precedes the -35 region of promoter P1. Beyond the translation stop codon UAA, a sequence of 69 bp can be folded into a hook-like stem-loop structure which probably functions as a transcriptional terminator. The ORF region of the gene bglA reveals about 90% homology with another beta glucanase gene, bglS of Bacillus subtilis C120 sequenced by Murphy et al. (1984). Three regions of frequent amino acid (aa) changes are indicated. However, the major difference between these is a set of deletions within the non-coding region separating the bglA gene from an unknown preceding ORF and by one deletion shortening the proposed signal peptide by three aa (Pro-Tyr-Leu-). The putative transcription terminator of gene bglA completely lacks homology with a B. subtilis bglS gene. The signification of deletions erasing the 'sacR-homology region' in B. amyloliquefaciens, which have been detected in proximity of the beta-glucanase gene of B. subtilis by Steinmetz and Aymerich (1986), is discussed. PMID- 3106159 TI - Bacillus subtilis phage phi 29 main promoters are efficiently recognized in vivo by the Streptomyces lividans RNA polymerase. AB - A DNA fragment from the Bacillus subtilis phage phi 29, containing the main early and late viral promoters, has been inserted upstream of the aminoglycoside phosphotransferase gene (neo) derived from the transposon Tn5 and present in a Streptomyces lividans promoter-probe plasmid. The phi 29 promoters are specifically recognized by the S. lividans RNA polymerase which initiates transcription in vivo at the same sites utilized in B. subtilis. Moreover, the viral promoters efficiently direct the synthesis of high levels of the APHII enzyme in S. lividans. PMID- 3106160 TI - Withholding treatment when death is not imminent. AB - Withholding or withdrawing life-sustaining treatment when death is not imminent goes beyond the issue of whether or not medical interventions are simply prolonging dying. It treads on the slippery slope of quality of life judgments. Courts, in keeping with a tradition of self-determination, continue to protect a patient's right to decide whether his or her life has quality enough to prolong it. Patients may refuse treatment despite predictably dire consequences of refusal, including death. This choice is not evidence per se of incompetence, despite any conflict with medical values. Judicious use of technology is urged when there is conflict between the worthy principles of prolongation of life and relief of suffering. The patient is the best judge of his or her life's quality. PMID- 3106161 TI - General principles for treatment planning for squamous cell carcinoma of the head and neck. PMID- 3106162 TI - Treatment planning of esophagus, stomach, rectum and pancreas. PMID- 3106163 TI - Technical and practical considerations in the radiotherapy of children. PMID- 3106164 TI - State of the art of high energy photon treatment planning. AB - A virtual revolution in computer capability has occurred in the last few years, based largely on rapidly decreasing costs and increasing reliability of digital memory and mass-storage capability. These developments have now made it possible to consider the application of both computer and display technologies to a much broader range of problems in radiation therapy including dose computation, therapy planning and treatment verification. Various similar methods of three dimensional dose computations in heterogeneous media capable of 2-3% accuracy are likely to be available, but significant work still remains especially for high energy X-rays where electron transport, and possibly pair production, needs to be considered. Innovative display and planning techniques are emerging and show great promise for the future. No doubt these advances will lead to substantially improved treatment planning systems in the next few years. However, it must be emphasized that for many of these applications a tremendous software and hardware development effort is required. Yet it is not clear whether the investments and efforts for improved capabilities and accuracies are warranted with respect to clinical outcome. The question must be addressed for the advancement in the practice of radiotherapy. PMID- 3106165 TI - Evaluation of treatment plans using dose volume histograms. PMID- 3106166 TI - Total body irradiation. PMID- 3106167 TI - Histochemical and morphological study of the regenerating corneal epithelium after limbus-to-limbus denudation. AB - Two typical characteristics of the limbal epithelium, namely, its high mitochondria content and histochemically proven proclivity towards carbonic anhydrase staining, were used to identify regenerating corneal epithelium as originating from the limbus. In addition, the period necessary for metaplasia of limbus epithelial cells into typical corneal epithelia was studied in light of these two criteria. It was proven that, on completion of the morphological transformation, after 7 days the positive carbonic anhydrase reaction was identifiable only in the basal cells of the limbus area, as in those of the control animals. It is concluded that in the early phase of reepithelialization, the forward-proliferating epithelial cells can be directly traced to the basal limbus epithelial cells. PMID- 3106168 TI - [Economic efficacy of hygienic recommendations in regional planning]. PMID- 3106169 TI - [Feasibility of the rapid evaluation of the toxicity of polymer materials and products made from them in hydrobionts]. PMID- 3106170 TI - [Experimental basis for the maximum allowable concentration of glutaraldehyde in the water of bodies of water]. PMID- 3106171 TI - Local immune response in gonorrheal cervicitis. PMID- 3106172 TI - Measurement of arachidonate and its metabolites extracted from human normal and malignant gastrointestinal tissues. AB - This is the first report of human gastrointestinal arachidonate and prostanoids measured quantitatively by gas chromatography-mass spectrometry (GC-MS) in extracts of human cancers and macroscopically normal tissues from the stomach and colon. There were microgram/g amounts of arachidonate, and the particularly high yield from the tumours may explain why they usually produce more prostaglandins than the normal tissues in which they arise. There was only a small conversion of the arachidonate into prostanoids. 6-Keto-PGF1 alpha was the most abundant metabolite measured, particularly in the tumour extracts, with smaller amounts of prostaglandins E2, F2 alpha and D2. PMID- 3106173 TI - Endometrial carcinoma: treatment of positive paraaortic nodes. AB - From 1974 to 1979, 138 patients who were treated for endometrial carcinoma underwent pelvic and paraaortic node dissection. Eighteen patients had positive paraaortic nodes (12.5%). Eleven out of twelve patients with microscopic disease and five out of six patients with gross disease received 5000 XRT to the paraaortic region as well as 4500 XRT to the pelvis. Megace at a dose of 160 mg daily was also given. Five-year survival rates were as follows: 66.7% (8/12) for microscopic disease, 16.7% (1/6) for gross disease. For Stage I microscopic disease, 66.5% (5/8), for Stage I gross disease 0% (0/4). For Stage II microscopic disease 66.7% (2/3) and for Stage II gross disease 50% (1/2). External RT to the paraaortic nodes appears to be beneficial for patients with microscopic disease in Stage I and Stage II endometrial carcinoma with minimal complications. PMID- 3106174 TI - Hexamethylmelamine in ovarian cancer after failure of cisplatin-based multiple agent chemotherapy. AB - A prospective study was initiated in 1979 to investigate the effect of hexamethylmelamine (HMM) as a second-line chemotherapeutic agent in the treatment of advanced adenocarcinoma of the ovary after failure of cisplatin-based multiple agent chemotherapy. Of 20 evaluable patients, there were 5 patients (25%) who had objective responses (4 complete and 1 partial). Four additional patients have remained without evidence of disease. Six of these 9 patients are still alive, disease free. There were significant differences (P less than 0.001) in both the progression-free interval and survival time for these 9 patients, 13.3 and 15.1 months, respectively, as compared to the 15 nonresponders, 0.8 and 5.8 months, respectively. There was no significant difference in survival between the 4 patients with stable disease and the 11 patients with progressive disease. Performance status less than 2 (P less than 0.05) and absence of clinically measurable disease at the time of entry into the study (P less than 0.05) were found to be significant variables with regard to determining outcome. Only 2 of 24 patients suffered severe enough side effects from the HMM to warrant its discontinuation. This study demonstrates that HMM at doses of 6-8 mg/kg/day for 21 out of every 28 days can induce a complete response and provide an extended disease-free interval and prolonged survival with tolerable side effects in a significant number of patients with ovarian cancer who have previously failed cisplatin-based multiple-agent chemotherapy. PMID- 3106175 TI - [Routine vaccination at the I. University Gynecologic Clinic. Rhesus prevention and rubella vaccination in the puerperium]. PMID- 3106176 TI - Evaluation of the genotoxicity of theobromine and caffeine. AB - Published data on the mutagenicity and genotoxicity of theobromine and caffeine were analysed by the Carcinogen Prediction and Battery Section (CPBS) method. In spite of some positive responses, these analyses did not predict for theobromine a potential for causing cancer by virtue of a genotoxic mechanism. Caffeine, on the other hand, clearly has potential for genotoxic carcinogenicity. The predictive performance of cost-effective batteries consisting of selected combinations of four assays was also evaluated. The predictions were similar to those derived when all the available test results were considered. PMID- 3106177 TI - Catecholamines and pituitary function. VI. Effect of different dopamine doses on TRH-induced prolactin release in women with pathological hyperprolactinemia. AB - The present study was designed to examine the effect of low-dose dopamine (DA) infusion rates (0.02 and 0.1 microgram/kg X min) on both basal and TRH-stimulated prolactin release in normal and hyperprolactinemic individuals. Sixteen normally menstruating women in the early follicular phase of a cycle and 23 hyperprolactinemic patients were studied. 0.1 microgram/kg X min DA was infused in 8 normal women and 15 patients with pathological hyperprolactinemia, while 8 normal controls and 8 patients received 0.02 microgram/kg X min DA TRH (200 micrograms, i.v.) was administered alone and at the 180th min of the 5-hour DA infusion in all controls and patients. A significant reduction in serum PRL levels, which was similar in normal women (-59.5 +/- 4.0%, mean +/- SE) and hyperprolactinemic patients (-48.2 +/- 5.5) was observed in response to 0.1 microgram/kg X min DA. In normal cycling women DA infusion significantly (P less than 0.02) reduced the PRL response to TRH with respect to the basal TRH test (delta PRL 45.0 +/- 7.0 vs. 77.9 +/- 15.4 ng/ml). On the contrary, the PRL response to TRH was significantly higher during 0.1 microgram/kg X min DA than in basal conditions in hyperprolactinemic patients, both in absolute (delta PRL 91.8 +/- 17.6 vs. 38.4 +/- 6.8, P less than 0.03) and per cent (198.5 +/- 67.6 vs. 32.1 +/- 7.5, P less than 0.02) values. A normal PRL response to TRH, arbitrarily defined as an increase greater than 100% of baseline, was restored in 11 out of 15 previously unresponsive hyperprolactinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106178 TI - Clinical and endocrinological characterization of two subjects with Reifenstein syndrome associated with qualitative abnormalities of the androgen receptor. AB - The androgen receptor in fibroblasts cultured from a biopsy of scrotal skin from 1 subject with Reifenstein syndrome has been found to be normal in amount and to bind dihydrotestosterone with normal affinity but to be qualitatively abnormal as evident by thermolability and instability upon ultracentrifugation. The family study of this subject and endocrine studies document androgen resistance in the index patient and his affected uncle. These findings provide evidence for X linkage of this disorder, and suggest that the mutations that give rise to this phenotype are probably allelic to the mutations of the androgen receptor that cause testicular feminization. PMID- 3106179 TI - Ectopic corticotrophin-releasing-factor and growth hormone releasing factor secretion: diagnosis using human pituitary cell culture. AB - Cell culture of human pituitary tissue has been used to diagnose a patient with Cushing's syndrome due to ectopic secretion of corticotrophin-releasing factor (CRF; case 1) and a case of acromegaly associated with ectopic secretion of a growth-hormone releasing factor (GRF; case 2). In both patients a pituitary tumour was not detected. Case 1 had a small cell carcinoma and symptoms of the ectopic ACTH syndrome, but in culture the carcinoma failed to secrete detectable ACTH. However, the culture medium used to maintain this carcinoma in vitro was found to contain a substance which stimulated ACTH secretion by human pituitary corticotrophs in cell culture. Radioimmunoassays and HPLC indicated that this substance had similar elution characteristics to human CRF and cross-reacted with antiserum to ovine CRF. Case 2 was found to have a lung tumour, the removal of which led to regression of her acromegalic symptoms. In culture, this tumour did not secrete GH, but did secrete a GRF. We conclude that the Cushing's syndrome and acromegaly, in cases 1 and 2, respectively, were due to ectopic secretion of CRF and GRF leading to hyperstimulation of the pituitary gland. PMID- 3106180 TI - Short-term pulsatile administration of luteinizing hormone releasing hormone in male adolescents with multiple idiopathic pituitary hormone deficiencies. AB - In order to define both level and severity of defect in patients with idiopathic multiple pituitary hormone deficiencies (MPHD) and to find out which patient might benefit from pulsatile LHRH substitution therapy, the effect of short-term pulsatile LHRH infusion in 6 affected male adolescents was studied. Controls were 9 boys with constitutional delay of puberty (CD). During a spontaneous nocturnal plasma profile LH and FSH levels were prepubertal with little evidence of pulsatile secretory LH activity in all MPHD patients. During short-term pulsatile LHRH stimulation (36 h), however, all showed a significant rise in mean LH and FSH levels (p less than 0.0001). Linear regression analysis revealed significant continuous increases of FSH (p less than 0.001) in all patients and of LH (p less than 0.01) in all but one patient. These changes were not accompanied by an increase of testosterone, androstenedione and DHAS levels. Since all MPHD patients showed steadily increasing gonadotropin levels if stimulated in a pulsatile manner, we conclude that the defect might only in part be located at the pituitary level. Long-term pulsatile substitution therapy with LHRH is likely to be successful in these patients as has been demonstrated in patients with known hypothalamic defect. PMID- 3106181 TI - Influence of short-term fasting on the pituitary-testicular axis in normal men. AB - To investigate whether short-term fasting affects serum testosterone (T) in normal subjects, 10 healthy men of normal weight were studied on two occasions: after an overnight fast (8 h), and after an additional 48 h of fasting. Blood glucose declined by 22 +/- 3% between the tests (p less than 0.001). Basal serum T fell from 8.7 +/- 0.7 to 5.7 +/- 0.8 micrograms/l (p less than 0.01), and LH from 6.9 +/- 0.8 to 5.0 +/- 0.7 U/l (p less than 0.01). Serum estradiol (E2) and FSH remained unaffected. To explore possible mechanisms behind the decreased basal release of T and LH, 9 small doses of glucose were given orally at regular intervals during a 56-hour fast to 9 additional normal men to maintain blood glucose levels. These men did not experience a fall in serum T or LH. Six additional normal men were given 50 micrograms GnRH intravenously after an overnight fast, and after a fasting period of 56 h. No acute increase in T was seen after the overnight fast, but after the 56-hour fast GnRH raised serum T by 55 +/- 14% (p less than 0.02). Moreover, fasting augmented the GnRH-induced LH response by 64 +/- 15% (p less than 0.02. These results imply that: short-term fasting exerts inhibitory influence on Leydig cell function via a mechanism which might involve a reduced hypothalamic and/or pituitary stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106182 TI - Male hypothalamic hypogonadism: induction of spermatogenesis by subcutaneous pulsatile gonadotrophin-releasing hormone. AB - Six male patients (aged 21-34 years) with isolated hypothalamic hypogonadism were given subcutaneous pulses of gonadotrophin-releasing hormone every 90 min for 14 74 weeks. The therapy produced an increase in testicular volume (4 patients) and a rise in serum luteinizing hormone, follicle-stimulating hormone, and testosterone levels in every patient. Motile sperm developed in 3 patients after a mean of 17 weeks, but were not seen in other patients who were less sexually developed after a mean of 31 weeks of therapy. Computerized tomography scans of the pituitary fossa revealed an empty sella in 4 patients and a partially empty sella in 2. Subcutaneous pulsing of gonadotrophin-releasing hormone is a simple and safe way of inducing spermatogenesis, but it is more likely to be successful in patients whose pubertal development is otherwise near completion. Previous human chorionic gonadotrophin and/or testosterone treatment does not interfere with and may benefit subsequent gonadotrophin-releasing hormone therapy. PMID- 3106183 TI - Possible direct effect of serotonin on pituitary prolactin secretion: in vivo and in vitro studies. AB - In this work we analyze the possibility of serotonin (5-HT)-releasing prolactin (PRL) through a direct action at the pituitary level. 5-HT (2 mg/kg i.v.) stimulates PRL secretion in hypophysectomized autotransplanted animals (HAG) significantly and this effect was not influenced by pretreatment with the dopaminergic antagonist domperidone. In perifused pituitaries, 5-HT administration (0.01, 0.1 and 1 microM for 90 min, or 1, 10, 100 microM for 15 min) was ineffective in stimulating PRL release. In pituitaries obtained from animals previously treated with the neurotoxic 5,7-dihydroxytryptamine (5,7-DHT) or vehicle and incubated in the presence of 5-HT (2.5, 5 and 10 microM), no response in PRL secretion was observed. These results suggested that 5-HT does not release PRL through a direct pituitary action, and that the effect observed in HAG animals could be mediated through the release of a PRL-releasing factor after 5-HT administration. PMID- 3106184 TI - Interferon-gamma production by peripheral blood mononuclear cells of patients with chronic liver disease. AB - We investigated the role of the interferon system in the pathogenesis of chronic liver disease. Interferon-gamma production by peripheral blood mononuclear cells was measured with an ELISA. While concanavalin A-stimulated and recombinant interleukin 2-stimulated production of interferon-gamma in patients with chronic active hepatitis and liver cirrhosis was significantly decreased when compared with that of controls (518 +/- 189 and 729 +/- 195 units per ml, mean +/- S.D.), there was also a lot of overlap. Addition of indomethacin to the cultures partially restored interferon-gamma production in patients with chronic active hepatitis and liver cirrhosis, indicating that suppressor function of monocytes was, in part, responsible for the diminished interferon-gamma production. Serial studies showed that interferon-gamma production rose during acute deterioration of illness, during treatment with interleukin 2 and with the improvement of clinical course. Interferon-gamma production was not different among hepatitis B e antigen or antibody positive, and non-A, non-B patients with chronic active hepatitis and liver cirrhosis. Our findings suggest that diminished interferon gamma production is associated with disease severity in chronic liver disease, irrespective of the hepatitis B virus carrier state. It would be interesting to compare the efficacy of treatment with interferon-gamma or interferon-gamma inducers such as interleukin 2 in chronic hepatitis B patients with and without decreased in vitro interferon-gamma production. PMID- 3106186 TI - Plight of elderly turns long-term care insurance into reality. PMID- 3106188 TI - Autopsy data and DRG reimbursement: another view. PMID- 3106187 TI - A model for human body composition by total body counting. PMID- 3106185 TI - Immunoprecipitation of the interleukin-2 receptor from Hodgkin's disease derived cell lines by monoclonal antibodies. AB - The nature of Hodgkin and Reed-Sternberg (H-RS) cells and their normal counterpart remains a matter of controversy. Our recent investigations have suggested that H-RS-cells derive from certain activated lymphocytes of either B or T cell origin. In keeping with this concept, we were able to demonstrate that in the majority of cases of Hodgkin's disease the interleukin-2 receptor (IL2-R) was detectable on H-RS-cells by three monoclonal antibodies (anti-Tac, Tu69 and ACT-1) with the sensitive alkaline phosphatase anti-alkaline phosphatase (APAAP) tissue staining procedure. In extension of these studies, we precipitated IL2-R antigen from two established permanent cell lines (L540 and L591) derived from patients with Hodgkin's disease. Although these cell lines are different in nature, in that the L540 line shows rearrangement for the T cell receptor beta chain gene and the L591 line displays rearrangement for immunoglobulin genes (gamma heavy and lambda light chain), the antigen precipitated by monoclonal antibodies against IL2-R exhibited a molecular weight of approximately 53 kd on the L591 line and 58 kd on the L540 line. Thus, these data strongly support the view that the labelling of H-RS-cells in tissue sections for IL2-R was not merely due to cross-reactivities of the two anti-IL2-R antibodies with a determinant of an unrelated structure but represents true IL2-R molecules. PMID- 3106190 TI - Recreation therapy for long-term patients. PMID- 3106191 TI - Director of patient programs. PMID- 3106192 TI - Peer counselling in a long-term care facility: people supporting people. PMID- 3106193 TI - Assignment of ribose carbon-13 resonances of puromycin and its analogs by 2D NMR: correlation between resonance position and electronegativity. PMID- 3106194 TI - Differential catalytic inhibition of lactoperoxidase and rat submaxillary peroxidase by antiserum raised against pure lactoperoxidase. PMID- 3106189 TI - Mammalian T-lymphocyte antigen receptor genes: genetic and nongenetic potential to generate variability. AB - T lymphocytes of higher vertebrates are able to specifically recognize a seemingly unlimited number of foreign antigens via their receptors, the T cell antigen receptors (TCRs). T lymphocytes mature by passing through the thymus and acquire antigen specificity by expressing the TCR molecules on their cell surface. Genetic and somatic diversification mechanisms give rise to the enormous degree of TCR variability observed in mature T cells: germline and combinatorial diversity as well as junctional and the so-called N-region diversity. In contrast to the situation in immunoglobulin genes somatic hypermutation does not seem to play a significant role in TCR diversification. It is argued here that the enzyme terminal nucleotidyl-transferase is potentially a major factor in generating the immense diversity. We propose furthermore that this enzyme ensures the flexibility of T cell responses to novel antigens by random insertion of so called N-region nucleotides. Apart from the physiological functions of TCR genes any involvement in the etiology of T cell neoplasia remains to be proven. PMID- 3106195 TI - Frequency analysis of augmented CTL production associated with Corynebacterium parvum-induced tumour regression. AB - A limiting-dilution frequency assay was employed to estimate the increased production of cytolytic T lymphocytes (CTL) associated with Corynebacterium parvum-induced regression of the P815 mastocytoma growing subcutaneously in semisyngeneic mice. It was found that intratumour C. parvum functioned to augment greatly the underlying concomitant production of CTL that occurs normally in response to a progressively growing untreated immunogenic tumour. The lymph node draining a C. parvum-treated tumour contained about eight times more CTL than the lymph node draining a control tumour. Intratumour C. parvum also caused a large increase in CTL production in the spleen and an increase in the number of CTL that could accumulate in a peritoneal exudate. At the peak of the anti-tumour response, the largest number of CTL was found in the draining lymph node (1.66 X 10(5], followed by the spleen (3.47 X 10(4) and by a 24-hr casein-induced peritoneal exudate (6.01 X 10(3]. Presumably, this greatly augmented production of CTL explains why C. parvum given intralesionally early enough during tumour growth can cause the regression of the weakly immunogenic P815 mastocytoma. PMID- 3106196 TI - A role of L3T4+ antigen in the Con A response of regenerating splenic L3T4+ T cells after Cy treatment. AB - The role of L3T4 antigens in the concanavalin A (Con A) response of regenerating spleen cells (Cy-SCs) after cyclophosphamide (Cy) treatment was studied. Anti L3T4 monoclonal antibodies (Mabs) markedly inhibited the Con A response of the regenerating Cy-SCs, which do not require Ia molecules expressed on accessory cells (ACs) for Con A activation. However, the Con A response of normal spleen cells (N-SCs), which do require Ia molecules on ACs, was not inhibited by the same Mabs, although the Con A response of N-SCs, as well as that of Cy-SCs, was demonstrated to be mediated by L3T4+ T cells. The optimal times for the inhibitory effect of anti-L3T4 Mab was 7 days after Cy treatment, when the number of spleen cells increased to a maximum following a regenerative phase. Its inhibitory effect was reduced by high concentrations of Con A, and was restricted to the early phase of the Con A response. A short time exposure of the Cy-SCs to the anti-L3T4 Mabs was sufficient to decrease the response to Con A. Our results cannot explain the hypothesis that the L3T4 molecule functions solely by interacting with non-polymorphic parts of Ia molecules on ACs. Taken together, these results and those of other groups of investigators suggest that Con A induced T-cell activation may be mediated by at least two or more interaction mechanisms involving either Ia or L3T4 molecules. Firstly, normal L3T4+ T cells may mainly interact with Con A involving self Ia molecules on the ACs. The extent of this interaction is sufficient to induce T-cell activation, and then does not need another L3T4 molecule. Secondly, the regenerating L3T4+ T cells may usually interact with the cell surface antigens of other T cells, including L3T4+, by the binding of both cell surface molecules to Con A in the absence of ACs, and then transmit a signal for T-cell activation. Anti-L3T4 Mabs may exert inhibitory effects somewhere in this process. PMID- 3106198 TI - Antigen presentation in brain: MHC induction on brain endothelium and astrocytes compared. AB - Primary cultures of rat brain endothelium and astrocytes were cultured in vitro, stimulated with interferon-gamma (IFN gamma), and the levels of MHC expression were then measured by an enzyme immunoassay (EIA). Class I expression is enhanced on brain endothelium by Day 1 following stimulation, and attains a plateau level of expression. Class II is normally absent, but starts to appear at Day 2, and continues to increase until Day 5. Class II rat I-A homologue is induced much more strongly than I-E, and the dose-response curves show that I-A expression is dependent on interferon dose within the range 2-500 units/ml, whereas class I enhancement is uniform over this range. The endothelium was compared with astrocytes, in regard to MHC induction. The surface density of class I and class II molecules was lower on the astrocytes in all conditions, and both class I enhancement and class II induction were in some cases slower to appear than on endothelium treated similarly. We also describe a pre-astrocytic cell line, C9, which shows strong I-E expression when stimulated with IFN gamma, but is apparently unable to express I-A. The implications of these findings for the development of immune reactions in the brain are discussed. PMID- 3106197 TI - T-cell activation by anti-idiotypic antibody: evidence for the internal image. AB - Human lymphoproliferative responses to a rabbit anti-idiotypic antibody (anti-Id TB71) and the corresponding mycobacterial protein antigen [38,000 molecular weight (MW)] have been investigated in a number of donors. It was found that responsiveness to anti-Id TB71 correlated with responder and non-responder (four subjects each) status to the 38,000 MW antigen. Furthermore, the induction of T cell proliferation by both the 38,000 MW antigen and the anti-Id TB71 was dependent on accessory cells. When taken together with the concordance between the 38,000 MW antigen and anti-Id responsiveness, this implies that the 38,000 MW antigen and anti-Id TB71 stimulate related, or at least partially overlapping, repertoires of T cells. This was confirmed by the finding that cloned T cells reactive with the 38,000 MW antigen also proliferated in response to the anti-Id TB71. These observations are readily explained if the anti-idiotypic antibody contains an internal image of, and can therefore mimic, the antigen. PMID- 3106200 TI - Decrease of elevated plasma leucine enkephalin levels by thyrotropin-releasing hormone in traumatic tetraplegics during spinal shock. PMID- 3106199 TI - Gene transfection of the HuLy-m2 (Leu-9) antigen into mouse L cells. AB - Human DNA was transfected into mouse L cells and tk+ HuLy-m2+ (= CD7+) transfectants isolated after growth in hypoxanthine, aminopterin, thymidine medium and repeated cloning. After several cycles of transfection, greater than 90% of HuLy-m2+ L cells could be detected, by rosetting and by cytofluorography, which showed the transfectants to have a density of CD7 two to five times that found on peripheral blood lymphocytes. Despite this, the 37 kd CD7+ dimer could only be identified with difficulty using cell-surface radioiodination and sodium dodecyl sulfate-polyacrylamide gel electrophoresis techniques. An antiserum was produced (C3H anti-HuLy-m2+ L cells) which, after absorption, was shown to react with HuLy-m2+ antigens present on human thymocytes and lymphocytes and on CD7+ transfected L cells. PMID- 3106201 TI - Comparison of latex agglutination inhibition test & bioassays for rapid estimation of serum gentamicin levels. PMID- 3106202 TI - Effect of intracerebroventricularly injected copper on rectal temperature of rabbits. PMID- 3106203 TI - Nutritional status in relation to socioeconomic level and nutritional knowledge. PMID- 3106204 TI - Nutrition policy in health plans. PMID- 3106205 TI - A study of ecological determinants of nutrition profile of preschool children in Ganderbal block of Kashmir Valley. PMID- 3106206 TI - Granule enzymes of human and rabbit polymorphonuclear leukocytes: an investigation of enzyme solubility. AB - Granules were isolated from both human and rabbit polymorphonuclear leukocytes (PMNs), and the quantity and solubility of certain granule enzymes compared. Lysozyme and alpha-mannosidase were found to be the most soluble enzymes in the granules of both species and could be released by lysis with 0.1% (v/v) Triton X 100. Alkaline phosphatase was also released by this lytic procedure, but its release required higher concentrations of Triton. The main difference between the species was found in the less-soluble enzymes that were retained as an insoluble complex after lysis by Triton X-100. Both myeloperoxidase and the neutral proteinase activity of rabbit PMNs were found to be highly insoluble, requiring 0.6 M sodium chloride for their extraction from this complex. The corresponding enzymes from human PMNs were more soluble, 0.15 M sodium chloride releasing the majority of the neutral proteinase activity. In addition, the insolubility of the rabbit neutral proteinase activity seemed to prevent its release from PMNs stimulated to degranulate in vitro by treatment with the calcium ionophore, A23187. Since rabbit PMNs were also shown to contain significantly less neutral proteinase activity than human PMNs, it would seem that the rabbit is a poor model for the study of PMN-mediated tissue injury in man. PMID- 3106207 TI - Total parenteral nutrition in neonates. A practical approach. PMID- 3106208 TI - [Clinical studies of peripheral venous parenteral nutrition. Effect of a 3.5% amino acid solution on postoperative metabolism with special reference to amino acid homeostasis]. AB - We studied 20 patients following vaginal hysterectomy until the third postoperative day. 10 patients (group I) in this randomized controlled study were infused only with water and electrolytes in a volume of 40 ml/kg BW. 10 patients (group II) received a 3.5% amino-acid solution with 6% carbohydrates in the same volume. In group II the nitrogen balance was significantly better than in group I. The nitrogen retention of 81% was judged as rather good. We have shown that there were no changes in the concentration of free plasma amino acids in group II, opposite we found significant changes especially in the branched-chain amino acids and alanine in group I. The normalization of metabolized amino acids and the normal concentration of the nonesterified fatty acids in group II demonstrated that the utilization of added amino acids took place not only in peripheral but also in visceral tissues. Our study indicates that the proven amino-acid solution can be recommended as peripheral-venous parenteral nutrition in the postoperative phase. PMID- 3106209 TI - [Assessment of risk status using nutrition diagnostic studies in surgical patients. 1. Determination of preoperative risk status in patients with stomach cancer]. AB - The diagnosis of the nutritional state is an essential component in determining the risk in patients with carcinoma of the gastrointestinal tract. Based on the results of multivariate, statistical analyses of numerous biochemical, anthropometric and immunologic parameters in 63 patients with gastric carcinoma, we can now simplify the determination of the nutritional state considerably. With the help of cluster analysis and together with clinical aspects, the nutritional state can be divided into 2 groups ('normal' and 'disturbed'), in contrast to the former classification ('normal' and several degrees of disturbed). Using discrimination analysis, a combination of parameters was found which allows a sufficiently good classification of subjects into either the 'normal' group or the 'disturbed' group, and in this way characterizes the nutritional state. Classification of the patients is accurate in 97% of the cases. 6 practically relevant parameters were determined with the discrimination analysis: serum albumin, serum transferrin, hemoglobin, upper arm circumference, triceps skin fold thickness, and the intracutaneous skin test quotient. The nutritional quotient, EQ2, can be determined from these values (in comparison to the nutritional quotient, EQ1, which is based on the 33 point evaluation scale), thus enabling a quantification of the nutritional state. The use of only individual parameters yields major differences from the results obtained with 6 parameters. However, a relation between the nutritional state and the existing immuno competence can be suspected when the results - especially of the skin test reactions - are in agreement with the results of the lymphocyte transformation. The test results of cell-mediated immunity in particular represent the extent of a reduced immunological reaction as opposed to the results of humoral immunity. Inclusion of less complex immunological investigation procedures must be reserved for future studies. The determination of daily urea production (urea production rate; dependent on protein supply) can be implemented as a practically relevant and reliable supplemental test for the evaluation of the existing metabolic state. PMID- 3106210 TI - [Parenteral use of a fat emulsion in the early postoperative period]. AB - Parenteral application of fat emulsions has been established as useful in long term artificial nutrition especially during weaning off the ventilator. In order to ascertain whether these advantages can also be proved in nonventilated patients in the immediate postoperative phase, alternatively carbohydrates versus a new fat emulsion were investigated. 30 patients were randomly allocated to three different nutrition regimens. The caloric and nitrogen supplementation was identical for all groups, while the carbohydrate and fat content was different. Group I: only carbohydrates (as caloric source), group II: high fat load (3 g/kg/day), group III: medium fat dosage (1.5 g/kg/day). Routine laboratory parameters as well as acid-base-status and fat metabolism were evaluated. While most of the routine parameters were not significantly different between the groups, triglyceride levels in serum were highest in group II but never exceeding 280 mg/dl (-x). Nitrogen balance as well as protein metabolism were significantly improved using regimen III, thus documenting the beneficial effect of a medium fat dosage in the immediate postoperative phase. Parenteral nutrition combining amino acids, carbohydrates and a fat emulsion seems to be the optimal postoperative regimen even in patients without ventilatory support. PMID- 3106211 TI - [Cholestasis in total parenteral nutrition. A review]. AB - Intrahepatic cholestasis is a frequent, however, unresolved complication of total parenteral nutrition in infancy. A frequency of 10-50% is reported. The concentration of serum bile acids seems to be a sensitive indicator for a beginning cholestasis. As typical histological alterations of the liver are considered: inflammatory portal reaction, fibrosis and proliferation of bile ducts. As important components of the obviously multifactorial etiology are considered: lacking oral alimentation, fetal bile acid synthetic pathways, amino acid toxicity, hypoalbuminemia, sepsis and substrate excess. PMID- 3106212 TI - Loading and maintenance dose for the determination of amino acid kinetics in plasma. AB - Intravenous bolus kinetics of amino acids and calculation of the kinetic parameters with an 1-compartment model revealed weak spots. Therefore, a new study design with a loading and maintenance dose and description of the plasma concentration time data with a 2-compartment model was created and studied in 9 healthy volunteers. After an over night fast the amino acid mixture Thomaeamin n 10% was infused with a loading dose of 20 mg AA/kg-1 X min-1 for 5 min and a maintenance dose of 5 mg AA/g-1 X min-1 for 55 min. The postinfusion period lasted 120 min. The PAA was determined with a Biotronic LC 6001 and the kinetic parameters were calculated by a Wang 2200 computer with the TOPFIT program package. The results showed mean values (means +/- SE) of the volume distribution between 4.7 +/- 0.6 till 9.4 +/- 1.8 liters, an elimination rate constant of 1.7 +/- 0.5 till 11.0 +/- 2.0 h-1, a total clearance of 186 +/- 37 till 846 +/- 66 ml X min-1 and transfer or endogenous production rate between 12 +/- 0.8 till 135 +/ 16 mumol kg-1 X h-1. The total transfer amounts to 17.6 mmol kg-1 X d-1 (= 2.2 g AA/kg-1 X d-1). It can be concluded that an optimal study design for the investigation of AA kinetics should increase the PAA levels 2-3 fold above basal during the infusion period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106213 TI - [Metabolism-oriented postoperative nutritional therapy--possibilities and limits in the use of glucose and xylitol]. AB - Carbohydrates and polyols are essential constituents of intravenous nutrition. In order to better understand the problems associated with the supply of energy sources, the physiology of enteral nutrition will be covered and compared with intravenous nutrition. This review article will deal with the metabolic actions of glucose and xylitol and derive therapeutical consequences for their intravenous use during different illnesses. PMID- 3106214 TI - Molecular cloning and expression of Rickettsia tsutsugamushi genes for two major protein antigens in Escherichia coli. AB - Several polypeptide antigens of Rickettsia tsutsugamushi are recognized by human or primate convalescent sera and may be important protective immunogens. Molecular cloning and expression of the genes encoding the 110K (110 kilodalton) and 56K polypeptide antigens of R. tsutsugamushi Karp were accomplished in the lambda gt11 expression vector system. Southern blot analysis with the cloned fragments for the 56K polypeptide antigen (0.7 kilobases) and the 110K polypeptide antigen (5.4 kilobases) confirmed that the insert DNA was rickettsial and not host cell in origin. Expression of a complete 110K polypeptide was shown to be independent of isopropyl-beta-D-thiogalactopyranoside induction, suggesting that an intact rickettsial promoter was operational. Epitopes of the 56K polypeptide were expressed as lac promoter-dependent beta-galactosidase fusion proteins. Polyclonal antibody, affinity purified against the recombinant 110K and 56K polypeptides, reacted with polypeptides of similar size in the Kato and Gilliam strains of R. tsutsugamushi. Group-reactive, but not strain-specific, monoclonal antibodies against the 56K polypeptide reacted with the cloned portion of the 56K polypeptide. Western blot analysis demonstrated that the cloned 56K Karp antigen gene product is recognized by human convalescent serum. PMID- 3106215 TI - Probing the surface of Neisseria gonorrhoeae: simultaneous localization of protein I and H.8 antigens. AB - Gonococcal outer membrane protein I and the neisserial antigen H.8 are being investigated for inclusion in a gonococcal vaccine. To determine the distribution of immunoaccessible protein I and H.8 molecules on the surface of viable gonococci and to approximate the accessibility of these antigens to vaccine elicited antibodies, immunologic probes composed of protein I- and H.8-specific antibodies linked to gold spheres were developed. When whole gonococci were exposed to the protein I and H.8 immunologic probes and examined by transmission electron microscopy, gold spheres clearly marked the surface of some of the gonococci, but not the surface of other gonococci from the same culture. The immunologic accessibility of gonococcal protein I or neisserial H.8 varied among gonococci. This diversity may affect the efficacy of a vaccine composed of these surface antigens. PMID- 3106216 TI - Gamma interferon as a crucial host defense against Rickettsia conorii in vivo. AB - Gamma interferon (IFN-gamma) plays an important role as a host defense in rickettsial infection. Swiss Webster mice, which are resistant to Rickettsia conorii (Malish 7 strain) infection, were treated with a monoclonal antibody against mouse IFN-gamma. When the antibody-treated mice were inoculated with 12 50% tissue culture infective doses of R. conorii, the mortality was 47% and the morbidity was 100%. None of the control mice, which received the same dose of R. conorii, died or became ill. The enumeration of rickettsiae in organs by direct immunofluorescence in paraffin sections demonstrated higher quantities of rickettsiae in the spleen had liver of IFN-gamma-depleted mice as compared with those of the infected controls. The kinetic analysis of IFN-gamma levels in sera showed depletion in the treated mice. These results indicate that IFN-gamma plays an important role as a host defense in the early stage of rickettsial infection. Survival of some mice despite continued treatment with antibody to IFN-gamma suggests that other immune mechanisms may also be important. PMID- 3106217 TI - Structural requirements of muramylpeptides for induction of necrosis at sites primed with Mycobacterium tuberculosis in guinea pigs. AB - Intracutaneous injection of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) in guinea pigs caused an extensive necrotic reaction in footpads prepared by injection of heat-killed Mycobacterium tuberculosis in water-in-mineral-oil emulsion. We examined a variety of analogs and derivatives of muramylpeptides for their ability to provoke this reaction. A maximum and a minimum structure responsible for the necrotic reaction were found to be N-acetylglycosaminyl beta(1-4)-N-acetylmuramyl-tripeptide (GlcNAc-MurNAc-L-Ala-D-isoGln-meso-A2pm) and MDP, respectively. An unexpected finding was that GlcNAc-MurNAc-tetrapeptides having L-amino acids at their C termini, unlike comparable compounds having C terminal D-amino acids, exhibited definite necrosis-inducing activity, probably due to their tendency to undergo in vivo degradation to GlcNAc-MurNAc-tripeptide. Introduction of some acyl groups, especially the stearoyl group, to the 6-O position of the muramic acid or the peptide moiety of muramylpeptides increased the necrosis-inducing activity of the parent molecules. However, this was not observed with 1-thio-muramic acid analogs of MDP. Modification of the alpha- or gamma-carboxyl groups of the glutamic acid residues of muramylpeptides tended to decrease their necrosis-inducing ability. Analogs and derivatives of muramylpeptides which are capable of inducing necrosis at a primed site, with few exceptions, exhibited powerful adjuvanticity against ovalbumin in guinea pigs. However, the reverse was not necessarily true. PMID- 3106218 TI - Macrophage activation as an immune correlate to protective immunity against schistosomiasis in mice immunized with an irradiated, cryopreserved live vaccine. AB - Immune responses against Schistosoma mansoni were evaluated in C57BL/6 mice injected with one of two populations of irradiated schistosomules, the larval preparations differing only in the degree of freezing-induced damage sustained upon cryopreservation. Mice injected with larvae which successfully withstood cryopreservation showed a significant reduction in worm burden following cercarial challenge. No protection was achieved in mice which received larvae damaged by a suboptimal thawing rate. Parallel comparison of several humoral and cellular responses in mice which received either inoculum revealed that induction of activated macrophages and production of macrophage-activating lymphokine activity were the strongest correlates to development of protective immunity. Protected mice also showed marginal 30-min skin test reactivity and weak but transient 24-h delayed-type hypersensitivity to a soluble adult worm preparation. In contrast, indistinguishable levels of circulating antibodies to soluble and tegumental antigens developed in the two immunization groups, and antigen stimulated lymphocyte blastogenic responses were strong and essentially equivalent in magnitude. These studies strongly suggested that in this new model for investigating anti-schistosome effector mechanisms, responses contributing to the development of activated macrophages may be essential for induction of protective immunity. PMID- 3106219 TI - An early response to lipopolysaccharide is the elicitation of macrophages specialized for antigen degradation with negative regulatory effects on the induction of specific immune responses. AB - The ability of macrophages to catabolize antigens is relevant both as a means to process complex antigens before presentation to T cells and as a way to down regulate immune responses by destroying the antigenicity of polypeptides. With these considerations in mind, we investigated the regulation of macrophage catabolic activity by lipopolysaccharide (LPS). Catabolic activity was quantitated by following the distribution and molecular form of 125I-labeled surface components of heat-killed Listeria monocytogenes after their uptake by macrophages. We compared the catabolic activity of macrophages from peritoneal exudates of mice injected intraperitoneally with saline or LPS and found that LPS elicited macrophages displayed a greatly enhanced (threefold) rate of catabolism. This increase in catabolic activity peaked 3 days after LPS injection and slowly declined thereafter, approaching a base-line level after 3 weeks. The enhancement of catabolic activity was under Lps gene control. Macrophages that were elicited 3 days after intraperitoneal injection of LPS rapidly destroyed the antigenicity of bacterial antigens, expressed low levels of Ia molecules, and processed and presented antigen slowly when tested as antigen-presenting cells in vitro. We also showed that an injection of LPS before infection with L. monocytogenes resulted in diminished development of T-cell reactivity to this organism. These results suggest that LPS elicits a macrophage population specialized for antigen degradation functions, with negative regulatory effects on the induction of specific immune responses. PMID- 3106220 TI - Induction and repression of outer membrane proteins by anaerobic growth of Neisseria gonorrhoeae. AB - Neisseria gonorrhoeae is generally considered to be an obligate aerobe; it can, however, grow in the absence of oxygen by anaerobic respiration by using nitrite as a terminal electron acceptor. The outer membrane protein compositions of aerobically and anaerobically grown N. gonorrhoeae strains were compared by one- and two-dimensional polyacrylamide gel electrophoresis. Anaerobically grown strains expressed at least three proteins (Pan 1 to Pan 3) at much higher levels than did aerobically grown cells. Conversely, at least five other proteins (Pox 1 to Pox 5) were found to be expressed at significantly higher levels in aerobically grown cells. None of the Pan or Pox proteins were heat modifiable, and none of the heat-modifiable protein IIs or other major outer membrane proteins (protein I, protein III, pilin, or H-8 protein) were significantly altered in expression by anaerobic growth. There were also no apparent differences in lipopolysaccharide composition in aerobically and anaerobically grown gonococci. The regulation of protein expression by oxygen availability suggests that anaerobic growth is a physiologically significant state for this organism. PMID- 3106221 TI - Screening of a recombinant mycobacterial DNA library with polyclonal antiserum and molecular weight analysis of expressed antigens. AB - A lambda gt11 expression library containing recombinant DNA from Mycobacterium tuberculosis was screened using hyperimmune anti-M. tuberculosis rabbit serum. The majority (22 of 29) of the recombinant clones selected by using polyclonal serum expressed three antigens that were previously identified by using mouse monoclonal antibodies, thus indicating the immunodominance of these proteins. Western blot analysis of the recombinant clones demonstrated that expression of these antigens is frequently independent of the formation of beta-galactosidase fusion proteins. The molecular weight of each expressed antigen can vary between clones and is not necessarily identical to that found in mycobacterial extracts. PMID- 3106222 TI - Injury to endothelial cells by phagocytosing polymorphonuclear leukocytes and modulatory role of lipoxygenase products. AB - Phagocytosis of microorganisms by polymorphonuclear leukocytes (PMN) is accompanied by inadvertent extracellular release of microbicidal products; this could result in tissue damage. We investigated whether PMN damages endothelial cells when phagocytosis of Staphylococcus aureus occurs on the endothelial surface and how this damage might be modulated. Damage was assayed by the measurement of cell detachment or cell lysis of cultured endothelial cells that were radiolabeled with 51Cr. Uptake of bacteria was accompanied by nonlytic detachment of endothelial cells from the monolayer. This effect was inhibited by alpha-1-antitrypsin but remained unaffected by scavengers of toxic oxygen species. During phagocytosis, PMN adhered to the endothelial cells. Adherence could be prevented by inhibition of the lipoxygenase pathway of arachidonic acid metabolism of the PMN with nordihydroguaiaretic acid. This inhibition also resulted in a marked decrease of the detaching activity of the PMN. The addition of exogenous leukotriene B4 during phagocytosis greatly enhanced the damage to the endothelial monolayer. These results indicate that phagocytosis of staphylococci by PMN is accompanied by injury to endothelial cell monolayers due to released lysosomal proteases and that products of the lipoxygenase pathway of PMN play a modulatory role in this injury. PMID- 3106224 TI - Growth inhibition of Trypanosoma cruzi in cultured murine myocardial cells mediated by a specifically induced lymphokine. AB - An in vitro model for studying the protection of mouse myocardial cells against Trypanosoma cruzi was developed. It was demonstrated that immune mouse lymphocytes stimulated with a specific antigen elicited a mediator which protected myocardial cells from newborn mice against T. cruzi infection. The substance responsible for this activity was sensitive to acid (pH 2) treatment. PMID- 3106223 TI - Genetic relationships and clonal population structure of serotype 2 strains of Neisseria meningitidis. AB - Two hundred and thirty-four strains of Neisseria meningitidis, including 94 serotype 2a, 111 serotype 2b, and 19 serotype 2c isolates, together with 10 isolates that were serotyped as 2 with polyvalent antiserum but did not react with monoclonal antibodies, were characterized by the electrophoretic mobilities of 15 metabolic enzymes. Of these enzymes, 14 were polymorphic, and 56 distinctive combinations of alleles at the enzyme loci (electrophoretic types) were identified, among which the mean genetic diversity per locus was 0.413, or about 75% of that recorded for the species N. meningitidis as a whole. Mean genetic diversity among electrophoretic types of the same serotype (2a, 2b, or 2c) was, however, on average, less than half the total species diversity, and no multilocus genotypes were shared between isolates of the different serotypes, which belong to distinctive clonal lineages. Recent temporal changes in the frequencies of recovery of pathogenic strains of serotypes 2a and 2b in South Africa and North America resulted from clone replacement in these populations rather than evolutionary modification of the serotype protein of the initially dominant clones. PMID- 3106226 TI - Adherence of Pseudomonas aeruginosa to cilia of human tracheal epithelial cells. AB - Pseudomonas aeruginosa was found to adhere selectively to cilia of human ciliated tracheal epithelial cells (TECs). P. aeruginosa bound in equal numbers to TECs of smokers and nonsmokers, with the mean adhesion index for binding of P. aeruginosa 492c to TECs of healthy individuals (+/- standard deviation) being 6.83 +/- 6.00 bacteria per TEC. PMID- 3106225 TI - Characterization of the binding of Pseudomonas aeruginosa alginate to human epithelial cells. AB - The alginate produced by Pseudomonas aeruginosa has been reported to play a role in the adhesion of this bacterium to epithelial cell surfaces, although some controversy concerning this role exists. To clarify this controversy, we investigated the ability of alginate to bind to human buccal epithelial cells (BECs) and human tracheal epithelial cells (TECs). Alginate from P. aeruginosa 492c bound to both BECs and TECs. Alginate from strain 492c was found to be multivalent and thus capable of agglutinating both BECs and TECs. The multivalency of alginate complicated the determination of the number of alginate specific receptors on the BEC and the apparent association constant (Ka). By using the analysis of Hogg and Winzor (Biochim. Biophys. Acta 843:159-163, 1985), an average valency of 2.6 BEC binding domains per alginate molecule was determined, and the maximum binding capacity per BEC was calculated to be 5.8 X 10(-4) micrograms, with a Ka of 4.1 X 10(-2) ml/micrograms. The binding of alginate to immobilized BECs (where only 50% of the BEC surface is exposed) yielded values of 2.52 X 10(-4) micrograms of alginate per BEC for the maximum binding capacity per BEC and a Ka of 3.30 X 10(-2) ml/micrograms. The alginate specific site on the BEC surface was trypsin sensitive. Alginate from P. aeruginosa 492a did not bind to BECs, differing substantially from that of strain 492c. The data presented here demonstrate that alginate purified from some strains of P. aeruginosa may bind to TECs and BECs in a defined, specific manner, whereas alginate from other strains does not, reflecting structural diversity in P. aeruginosa alginates. PMID- 3106227 TI - [Clinical study of the effectiveness and tolerance of norfloxacin in the therapy of complicated urinary tract infections and in long-term prevention of recurrent urinary tract infections]. AB - The efficacy and tolerance of norfloxacin in the treatment of complicated urinary tract infections and in low dose long-term prophylaxis over six months for recurrent UTI were investigated in 60 and 27 patients, respectively. In the prophylaxis group, compliance with medication was controlled weekly using Mecur BT. Five to nine days after treatment, the urine was sterile in 50 out of the 60 patients treated (83.3%); relapse occurred in six patients and was associated with development of resistance in two. Four patients suffered re-infection within the study period. Failure of treatment was closely related to persisting complicating factors in the urinary tract. The overall tolerance of norfloxacin was satisfactory. However, there was one severe allergic reaction. During the total 391 weeks of low dose long-term prophylaxis given to 27 patients, only one break-through infection occurred. Yet compliance studies proved that antimicrobial activity was present in the urines of less than 50% of the patients. During prophylaxis, the rate of infection was reduced from three to four to 0.13 to 0.05 infections/patient/year. There was no development of resistance in the isolates from these patients. Only two adverse reactions were observed. PMID- 3106229 TI - [Effect of Pseudomonas immunoglobulin on the antibacterial activity of human phagocytes]. AB - The in vitro influence of a pseudomonas immunoglobulin in active and inactivated serum on the bactericidal activity and phagocytosis of human polymorphonuclear leukocytes was evaluated against Pseudomonas aeruginosa. No lysis of the bacteria could be found in either serum, however, the bactericidal activity of the leukocytes was significantly enhanced in active serum (p less than or equal to 0.05); whereas no effect was measurable in inactivated serum. Phagocytosis could be increased in concentrations of 10% immunoglobulin, (equivalent to 5 mg IgG/ml); however, a concentration of 15% showed a lower phagocytosis index which was comparable to that in the 5% preparation. This immunoglobulin proved to be able to support the bacterial phagocytosis and killing of P. aeruginosa by human polymorphonuclear leukocytes in vitro. PMID- 3106228 TI - [Significance of Pseudomonas aeruginosa virulence factors in acute and chronic Pseudomonas aeruginosa infections]. AB - The virulence of Pseudomonas aeruginosa is multifactorial and caused by several extracellular enzymes and other substances. The importance of these virulence factors for the pathogenesis of human P. aeruginosa infections is dependent on the type of infection. For acute, systemic infections in immunocompromised patients, exotoxin A, alkaline protease and elastase are essential virulence factors. In localized infections (e.g., cystic fibrosis) they seem to be of minor importance, since they are neutralized by specific antibodies in immune complexes, and in the case of exotoxin A cleavage by proteinases from polymorphonuclear leukocytes occurs. The rhamnolipid of P. aeruginosa which has been detected in sputa of patients with cystic fibrosis evades the host's immune response and has to be regarded as a potential virulence factor together with the phenazine pigments, also in chronic P. aeruginosa infections. PMID- 3106230 TI - [Pseudomonas aeruginosa immunoglobulin in experimental pneumonia]. AB - A guinea pig model of experimental Pseudomonas aeruginosa pneumonia was used to evaluate factors affecting the efficacy of passive immune therapy with Psomaglobin N, a hyperimmune P. aeruginosa globulin. Animals treated 2 h after infection with a single intravenous infusion of Psomaglobin N, 500 mg/kg, demonstrated 33% survival. Lower dosages were less effective and no survivors occurred among albumin-treated controls. Treatment with Psomaglobin N was effective if given 2 h or 8 h after infection but not if delayed until 24 h after infection. Animals rendered neutropenic with cyclophosphamide did not survive if treated with Psomaglobin N alone. However, when Psomaglobin N was added to tobramycin treatment, a significant increase in survival occurred (86%) as compared to that observed with tobramycin alone (43%) (p less than 0.05). We conclude that Psomaglobin N may offer a useful therapeutic option in management of P. aeruginosa pneumonia. PMID- 3106231 TI - [Pseudomonas aeruginosa as the pathogen in opportunistic infections]. AB - Pseudomonas aeruginosa, in spite of being an ubiquitous microorganism, rarely colonizes healthy individuals. Hospitalization, as well as the length of time spent in hospital, significantly increase the rate of colonization, especially in immunocompromized patients. Antibacterial chemotherapy or prophylaxis together with invasive diagnostic procedures favour colonization and infection with P. aeruginosa. Immune deficiencies and adverse interactions of P. aeruginosa with the immune system facilitate infection. Thus, a number of exogenous as well as endogenous factors and their interactions favour infection of patients with P. aeruginosa. PMID- 3106232 TI - [Experiences with a Pseudomonas immunoglobulin in artificially respirated patients with Pseudomonas pneumonia at a surgical intensive care unit]. AB - In a clinical trial, the efficacy of a Pseudomonas immunoglobulin was studied in ten ventilated patients suffering from Pseudomonas pneumonia. Compared to ten patients of a previous study who had received a polyvalent immunoglobulin (control group), patients treated with Pseudomonas immunoglobulin fared better with respect to clinical success and duration of treatment, the period of antibiotic treatment being significantly shorter than in the control group. PMID- 3106233 TI - [Use of Pseudomonas immunoglobulin in artificially respirated patients at an interdisciplinary surgical intensive care unit]. AB - The clinical efficacy and safety of a new pseudomonas hyperimmune globulin for intravenous administration were examined in 30 patients in a prospective randomized study. Although the statistical evaluation of the measurable parameters did not show relevant differences between the therapy group (n = 15) and the controls (n = 15), the clinical course of the disease was markedly better in patients treated with hyperimmune globulin. In the control group, three patients died from Pseudomonas aeruginosa infections, but none in the therapy group. The preparation was very well tolerated. PMID- 3106235 TI - Infection and trauma: an overview. PMID- 3106234 TI - [Prevention using a Pseudomonas immunoglobulin in burn patients]. AB - Pseudomonas aeruginosa belongs to the most frequent pathogens isolated from patients with burns. In a mouse model for artificial burns it was found that prophylactic administration of a hyperimmune globulin with antibody titres against P. aeruginosa (Fisher immunotypes 1, 2, 4 and 6) reduced mortality. Therefore, the prophylactic administration of Pseudomonas immunoglobulin was examined in a prospective randomized study in two groups of 13 patients each. Severely burned patients with at least second degree burns over 30% to 70% of the total body surface area received 250 mg Pseudomonas immunoglobulin/kg body weight by the intravenous route between days 3 and 13. After treatment, plasma IgG levels were significantly raised between days 7 and 16 as compared to the controls, yet the incidence of infections caused by P. aeruginosa was not reduced. However, only two of the six infected patients, developed septicaemia, whereas in the control group, local Pseudomonas infection led to septicaemia in five out of seven patients. The number of septicaemic Staphylococcus aureus infections was also lower in patients on immunoglobulin prophylaxis, with two cases compared to four cases in the control group. Due to the limited number of cases studied, statistically significant results could not be obtained, however, there was a positive trend in favour of Pseudomonas immunoglobulin treatment. PMID- 3106236 TI - Anti-idiotypic antibodies as staphylococcal enterotoxin receptor probes on monkey mast cells. AB - The immediate-type skin reaction in unsensitized monkeys upon challenge with staphylococcal enterotoxin B (SEB) was studied to define the role of mast cell receptors in the action of the toxin. For this purpose anti-idiotypic antibodies (anti-Id) were raised in BALB/c mice against monoclonal anti-SEB antibodies and purified by idiotype affinity chromatography. Anti-Id completely abolished skin reactions upon challenge with SEB without having biological functions itself. The data are compatible with the view that receptors for staphylococcal enterotoxin actually exist on the mast cell membrane of primates and anti-Id may be of potential value to influence the course of staphylococcal enterotoxin-mediated effects. PMID- 3106237 TI - Accessory molecules in T lymphocyte activation. AB - The currently accepted hypothesis used to explain the role of Lyt-2 and L3T4 in T cell activation proposes how these molecules interact with class I and II major histocompatibility complex molecules, respectively, on the antigen-presenting or target cell, to increase the avidity of binding of the antigen-specific T cell receptor. This has been tested using two antigen-specific, class II-restricted T cell clones expressing both Lyt- and L3T4. Inhibition of function was observed only with monoclonal antibody against L3T4, not Lyt-2. One interpretation of these results is that L3T4 and the class II-restricted T cell receptor can physically associate during T cell activation to form a multi-molecular complex from which Lyt-2 is excluded. PMID- 3106238 TI - Activation of basophils and mast cells for mediator release. AB - Biochemical events involved in both IgE-dependent and IgE-independent mediator release from basophils and mast cells were analyzed. The results revealed that bridging of IgE receptors activates a variety of membrane-associated enzymes, such as serine protease, phospholipase C, methyltransferases and adenylate cyclase, resulting in the stimulation of phosphatidylinositol (PI) turnover and a transient increase in both phospholipid methylation and intracellular cAMP. Mobilization of intracellular Ca2+ monitored by Quin-2 fluorescence is detected within 5 s after antigen challenge and appears to be the earliest intracellular change detectable after receptor bridging. Stimulation of PI turnover results in the generation of inositol 1,4,5-triphosphate (IP3) and of 1,2-diacylglycerol (DAG), which in turn activates protein kinase C. Evidence was obtained that the guanyl nucleotide (GTP)-binding protein Ni is not involved in the transduction of IgE-mediated triggering signals for mediator release. Although the sequence of enzyme activation following receptor bridging is not clear, the results suggest that the mobilization of intracellular Ca2+ is a crucial initial signal in the IgE-mediated activation of basophils and mast cells. In the mediator release induced by IgE-independent stimuli, enzymes involved in the mediator release are different from one stimulus to another. The results indicate the presence of multiple biochemical pathways for mediator release from basophils and mast cells. PMID- 3106239 TI - In vitro IgE synthesis induced by human T cell clones in normal B cells and its suppression by heterogenous T cell populations. AB - Thirty-four out of 119 human T cell clones established from tonsillar or peripheral blood T cell suspensions of 3 nonallergic individuals were able to induce normal B cells to synthesize remarkable amounts of IgE in vitro. The activity of these clones was apparently mediated by triggering of the monomorphic molecular complex CD3 immediately before or during their incubation with the target B cells. The addition to the cultures of mitogen-stimulated autologous unfractionated T cells inhibited in a dose-dependent fashion, the T cell clone induced IgE, but not IgG, synthesis. PMID- 3106240 TI - Current concepts in the pathogenesis of occupationally induced allergic pneumonitis. PMID- 3106242 TI - Purification, identification and elimination of a natural human serum antibody with cytotoxic effect on guinea pig thymocytes. AB - Normal human sera contain one or several factors cytotoxic for normal guinea pig thymocytes, and when serum is precipitated with ammonium sulphate (60% saturated) and the precipitate dissolved and dialyzed, the activity is preserved. Gel chromatography with Sephadex G-150 and Sepharose CL-6B indicated a molecular weight of approximately 900,000 daltons. The active fractions contained a high amount of IgM according to single radial immunodiffusion and two-dimensional gel electrophoresis. Quantitation of the IgM band in one-dimensional gel electrophoresis preparations by gel scanning indicated that IgM accounted for 65% of the eluted proteins in active fractions. Purified human IgM from myeloma patients eluted as the active factor during gel chromatography. Elimination of IgM from serum by affinity chromatography eliminated the cytotoxic activity. The serum could also be inactivated by heating. The mixing of IgM-depleted serum with either polyclonal IgM or heat-inactivated serum restored the activity. Thus, the cytotoxic activity is due to IgM antibodies plus a heat-labile component (presumably complement). The presence of the cytotoxic activity in autologous (guinea pig) serum was recently demonstrated. The possible functional role of these antibodies in the elimination process of a large number of cortical thymocytes is suggested. PMID- 3106241 TI - Effect of schistosome-derived inhibitory factor on the cell cycle of T lymphocytes. AB - A schistosome-derived inhibitory factor (SDIF) with immunosuppressive properties has been investigated for its effect on human T cell proliferation. We show here that SDIF has no effect on the process of lymphocyte activation because peripheral blood leukocytes (PBL) stimulated with lectin in the presence of SDIF increased normally their RNA content and showed normal acquisition of interleukin 2 (IL-2) and transferrin receptors. IL-2 production was not altered by SDIF but utilization of IL-2 was decreased, suggesting that SDIF blocked cells before or in the early s phase. Jurkat T cell line cells physically enriched for G1 cells were also more susceptible to SDIF inhibition. On the contrary, normal PBL or Jurkat cells which were already in the s phase were no more inhibited by SDIF. While SDIF has no effect on T lymphocyte activation and on production of regulatory lymphokines it selectively blocks T cell proliferation at G1 transition of the cell cycle. PMID- 3106243 TI - E-rosetting of guinea pig lymphocytes with lyophilized rabbit red cells after treatment with papain and glutaraldehyde. AB - Guinea pig lymphoid cells were reacted to form spontaneous rosettes (E-rosettes) with rabbit red blood cells before and after treatment with papain or a very low concentration (0.01%) of glutaraldehyde alone or both. The papain-glutaraldehyde treated cells showed as high ability as papain-treated cells to rosette with lymphoid cells prepared from thymus, spleen, lymph node and peripheral blood of guinea pigs. Moreover, papain-glutaraldehyde-treated red cells were lyophilized and stored for 1 year without any change in their ability to form E-rosettes with these lymphoid cells. Binding between lymphocytes and treated or nontreated red cells was completely inhibited by specific anti-guinea pig thymocyte serum. Furthermore, a lymphocyte population enriched for B cells from lymph nodes or leukemic cells of strain 2 guinea pigs (B cells) did not show any substantial E rosettes with nontreated or treated red cells. Scanning electron microscopy revealed no surface alteration in the treated cells when compared to those in nontreated red cells. PMID- 3106244 TI - Forward motility protein (FMP): localization in hamster epididymal spermatozoa. AB - The presence of FMP was investigated by immunocytochemistry in spermatozoa from the hamster caput and cauda epididymis. Spermatozoa from the caput showed no staining whereas spermatozoa pre-incubated with FMP were stained on the acrosome. Pre-treatment of the same sperm with epididymal plasma induced staining on the principal piece of the flagellum. Spermatozoa from the cauda were stained without previous incubation both on the acrosome and on the principal piece of the flagellum. These results suggest that the action of FMP, which prevents head-to head agglutination of motile spermatozoa and allows acquisition of forward motility, may be due to at least two proteins. The first localizes to the acrosome during epididymal transit (anti-sticking factor), whilst the second localizes to the principal piece of the flagellum (forward motility initiation factor). PMID- 3106245 TI - Induced hyperprolactinaemia does not alter FSH binding or ABP secretion in the rat testis. AB - The effects of induced hyperprolactinaemia in male Wistar rats were studied by grafting two pituitary glands under the kidney capsule. Transplants were performed at 15 and 60 days of age, and rats killed 4 weeks later when tissue and serum samples were obtained. Serum concentrations of LH were reduced significantly in rats grafted at 60 days of age, whereas no change was observed in rats grafted at 15 days of age. Serum testosterone levels were slightly suppressed only in the older group of grafted rats. Testicular FSH receptors and the epididymal content of androgen-binding protein (ABP) were not modified by induction of hyperprolactinaemia. The results indicate that hyperprolactinaemia was not associated with changes in at least two functional parameters of the tubular compartment of the rat testis. PMID- 3106246 TI - Testicular vascular resistance in the rat after intratesticular injection of an LRH-agonist. AB - Testicular vascular resistance (TVR) was estimated 1, 2, 4 and 8 h after unilateral intratesticular injection of 1 or 10 ng of an LRH-agonist (A). The lower dose had no effect on plasma levels of testosterone or LH, but there was a significant increase in TVR 2 h after injection when compared to the vehicle injected contralateral testis. Injection of 10 ng LRH-A induced an increase in plasma levels of LH at 1 and 2 h after treatment and in the plasma levels of testosterone at 1, 2 and 4 h. In the same rats there was a decrease in TVR at 2, 4 and 8 h after LRH-A treatment compared to the contralateral testis. It is concluded that LRH-A can have both stimulatory and inhibitory effects on TVR in the rat and that the direction of this effect may be related to the ambient level of LH. PMID- 3106247 TI - The activation-associated antigen 4F2 predicts patient survival in low-grade B cell lymphomas. AB - Expression of the activation-associated 4F2 antigen, transferrin receptor and interleukin-2 (IL-2) receptor on suspended cells from 75 biopsied low-grade non Hodgkin lymphomas (L-NHL) of B-cell origin was correlated to patient survival, clinical prognostic parameters and estimated DNA synthesis. 4F2 antigen expression correlated significantly with poor patient survival, high DNA synthesis and transferrin receptor expression. Transferrin receptor expression was associated with high DNA synthesis and treatment response, but not with patient survival. On the other hand, IL-2 receptor was correlated neither to patient survival nor to other studied markers for cell activation, but seemed to be expressed on certain subsets of lymphomas. We suggest that monoclonal antibody (MAb) against the activation-associated 4F2 antigen could be used to select patients with L-NHL for aggressive chemotherapy. PMID- 3106249 TI - Clonal rearrangement of the T-cell receptor gene and the diagnosis of mycosis fungoides. PMID- 3106248 TI - Outpatient therapy of bite wounds. Demographic data, bacteriology, and a prospective, randomized trial of amoxicillin/clavulanic acid versus penicillin +/ dicloxacillin. AB - Thirty patients received penicillin (17 of these also received dicloxacillin) and 31 received amoxicillin/clavulanic acid in a randomized study of the outpatient management of bite wounds. A wide variety of aerobic (185 strains) and anaerobic (47 strains) bacteria were isolated from these wounds. The control and study regimens were equally effective. There were four therapeutic failures in all. Aggressive wound management along with antimicrobial therapy led to a 87-96% cure rate. Loose stools or diarrhea was a more frequent side effect with amoxicillin/clavulanic acid than with penicillin +/- dicloxacillin. PMID- 3106250 TI - Lectin binding to formalin-fixed paraffin sections of human endometrium. AB - The binding of fluorescein isothiocyanate conjugated concanavalin A (Con A), Triticum vulgaris (WGA), Glycine maximum (SBA), dolichos biflorus (DBA), Ulex europaeus (UEA), Arachis hypogaea (PNA), and Ricinus communis (RCA) to human proliferative, secretory, and atrophic endometrium was studied. The binding of Con A and WGA increased markedly during the progression of the endometrium from the proliferative to the secretory phase. Triticum vulgaris seemed to bind to the secretion and was transported from the glandular cells to the glandular lumen during the secretory phase. Glycine maximum bound to the surface epithelium but not to the glandular cells. Some of the stromal cells showed binding with various lectins that also partly followed the endometrial cycle. The binding of the lectins in formalin-fixed paraffin sections as compared with that in frozen sections showed only slight differences that were restricted to SBA and DBA. The changes in the lectin binding of the endometrium reflect morphological and functional changes and lectin staining might possibly be used in further studies relating to functional disturbances of the endometrium. PMID- 3106251 TI - Metabolic profile in obese women with the polycystic ovary syndrome. AB - Nine obese women with oligo- or ameno-rrhoea, all with clinical and endocrinological signs of polycystic ovary syndrome (PCO) were submitted to metabolic studies. Their mean weight was 96 kg and their mean plasma testosterone concentration was 3.5 nmol/l. A group of nine obese, regularly menstruating women of similar age and degree of obesity (mean body weight 102 kg) served as controls. Their mean testosterone concentration was 1.9 nmol/l. The high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations in plasma were significantly lower in women with PCO than in control women. Furthermore, in the whole group the testosterone level showed significant inverse relationships to HDL-cholesterol (r = -0.64; P less than 0.01) and apo A-I (r = 0.59; P less than 0.01). The lipoprotein lipase activity (LPLA) in adipose tissue was lower in the women with PCO than in the control group with levels similar to those found in adipose tissue in men. There was an inverse relationship between the testosterone concentration in plasma and LPLA in adipose tissue (r = -0.51; P less than 0.05). The fat cells were of similar size at different regions in the women with PCO but showed marked differences in the control subjects who had much larger cells at the femoral than the abdominal site. The results show that the hyperandrogenism in PCO affects adipose tissue LPLA which could explain the lower HDL cholesterol values in women with PCO. PMID- 3106252 TI - Low serum free T3 concentrations in postobese patients previously treated with very-low-calorie diet. AB - Thirteen postobese patients with stable body weights were studied and compared with obese patients and normal subjects. Six had previously been treated with a very-low-calorie diet (VLCD) whereas seven had been treated with gastroplasty (GP). The median observation time of post-obesity was 20 months for GP patients, but significantly (P less than 0.001) shorter by 2 months in VLCD patients. The median serum concentration of free triiodothyronine (T3) was significantly (P less than 0.005) reduced in the postobese VLCD patients (3.4 pmol/l) but normal in postobese GP patients (4.2 pmol/l) and obese patients (4.5 pmol/l). The serum level of total T3 was correspondingly lowered in the postobese VLCD patients. Also the postobese GP patients had a small, but significant (P less than 0.01) reduction in the median serum concentration of total T3 suggesting a slight decrease in the binding capacity. The serum levels of thyroxine-binding globulin and thyroxine-binding prealbumin were normal in both postobese and obese patients. Furthermore, the serum levels of thyroxine were normal showing that the postobese patients were euthyroid. The study shows that serum concentrations of T3 are not associated with body weights and low serum concentration may be seen in postobese patients after VLCD. PMID- 3106253 TI - Inhibition of mammalian host cell infection by insect-derived, metacyclic forms of Trypanosoma cruzi in the presence of human or rabbit anti-T. cruzi antibodies. PMID- 3106254 TI - Protein fraction from Trypanosoma cruzi infected spleen cell supernatants with immunosuppressive activity in vitro. PMID- 3106255 TI - [What is established in the therapy of heart failure?]. PMID- 3106256 TI - Spontaneous inhibition of bacterial growth in experimental gram-negative endophthalmitis. AB - We compared the growth patterns of gram-negative bacilli in the vitreous humor (experimental endophthalmitis in rabbits) and in a subcutaneous site of infection (croton oil pouches in rats). In untreated animals, inoculation of Klebsiella pneumoniae or Pseudomonas aeruginosa into either site was followed by a period of rapid bacterial multiplication. Thereafter, the numbers of bacteria in the vitreous humor fell spontaneously, whereas those in the subcutaneous site remained stable. During treatment with antibiotics, there was a decline in the numbers of bacteria in both sites. However, once the drug had been eliminated, the numbers of bacteria remained low in the vitreous humor but increased in the subcutaneous site. These findings suggest that during the course of infection, there was depletion of an essential bacterial nutrient or accumulation of an antibacterial substance in the vitreous humor but not in the subcutaneous site. To examine some of these possibilities, we made biochemical measurements during the course of untreated infection. In general, the biochemical changes in the two sites were similar except that the pH fell to about 6.6-6.8 in the vitreous humor but remained above 7.0 in the subcutaneous site. None of the biochemical changes that we observed seemed likely to account for the spontaneous decline in bacterial numbers in the vitreous humor. Further study is warranted to determine the cause of the antibacterial effect in the vitreous humor during the course of experimental bacterial endophthalmitis. PMID- 3106257 TI - Effect of size and lipid composition on the pharmacokinetics of intravitreal liposomes. AB - We investigated the influence of size and lipid composition on the pharmacokinetic behavior of liposomes and their contents in the rabbit eye. Small and large unilamellar vesicles (SUV and LUV), prepared with and without cholesterol in the membrane, were injected intravitreally in rabbits. The vesicles were labelled with 125I and contained 51Cr-EDTA in the aqueous compartment. The mode of elimination of the vesicles from the vitreous humor is uncertain but may be via the anterior route; 51Cr-EDTA, like gentamicin, probably is eliminated by the anterior route. The rate of clearance of the lipid label appeared to be related to the size but not to the cholesterol content of the liposomes. Liposome-encapsulation prolonged the half-life of 51Cr-EDTA by up to 11-fold in the vitreous humor of normal eyes. The prolongation was greatest with cholesterol-containing vesicles, presumably because these are most stable, and was somewhat greater with large than with small vesicles. For SUV and LUV, the rate of elimination of 51Cr-EDTA from the normal eye was determined mainly by the rate of leakage from the liposomes, whereas for SUV-cholesterol and LUV cholesterol, it was determined mainly by the rate of clearance of the liposomes themselves. Both 51Cr-EDTA and liposomes (125I label) had a shorter half-life in infected than in normal eyes. Encapsulation of 51Cr-EDTA prolonged its half-life by up to sevenfold in infected eyes; the effect was greatest with cholesterol containing vesicles. These results suggest that both the structure of the liposome and the state of the eye may markedly affect the pharmacokinetic behavior of intravitreal liposomes. PMID- 3106258 TI - Scrapie incubation periods and end-point titers in mouse strains differing at the H-2D locus. AB - In extending findings on the influence of the mouse H-2D locus on the scrapie incubation period, we showed that with the intracerebral (i.c.) route of injection, SJL and NZW mice (s and z alleles, respectively) had shorter incubation periods than C57BL mice (b allele) at several concentrations of two scrapie strains, ME7 and 139A. The three mouse strains have the same Sinc genotype, s7s7. Incubation period data among the three mouse strains after intraperitoneal (i.p.) injection revealed a different rank order of incubation periods from that seen after i.c. injection. End-point titers in the three mouse strains were similar after i.c. injection, but both scrapie strains yielded very low titers in NZW mice after i.p. injection. There were marked differences between 139A and ME7 incubation periods after both i.c. and i.p. injections in the three mouse genotypes, providing an additional parameter that distinguishes these two scrapie strains. PMID- 3106259 TI - Low-dose aurothioglucose in pemphigus vulgaris. AB - Three female Jewish patients with typical pemphigus vulgaris involving the skin and the oral mucosa were managed with weekly i.m. aurothioglucose injections less than or equal to 25 mg. After obtaining a remission, the interval between injections was gradually lengthened. Fluocortolone was given in the first few weeks in decreasing dosages, starting with 60 mg/day. The two younger patients, aged 50 and 39, were in complete remission on follow-up 42 and 27 months later, respectively. They currently receive 25 mg of aurothioglucose every 6 to 8 weeks. One had had transient parotitis while on therapy. The other had had benign familial leukopenia, prior to the institution of gold therapy, and her total leukocyte and differential counts remained constant. The third patient, aged 80, who had widespread and deteriorating pemphigus, was switched to a steroid azathioprine regimen because gold did not improve her condition quickly enough. Thus, some pemphigus patients may experience prolonged clinical remissions and improved quality of life on low doses of gold. PMID- 3106260 TI - Temporal firing patterns of single units, pairs and triplets of units in the auditory cortex. AB - The spontaneous and acoustically driven activities of single units, pairs and triplets of units in the auditory cortex were analyzed. Data were obtained in two sets of experiments from nonbehaving awake cats and from a behaving monkey. The results of the two sets of experiments indicated that neighboring neurons usually fire independently. The weak correlations found between pairs of adjacent neurons were mostly indicative of a common input driving both units. In some cases, signs of synaptic interaction between the neurons were found. When triplets of units were considered, it was found that several independent inputs exist, even within a small group of adjacent neurons. When such small groups of neurons were studied in the behaving monkey, it was found that the temporal firing pattern of single neurons and the interactions between pairs of neurons were in some cases dependent on the behavioral state and on the sensorimotor association. PMID- 3106261 TI - [Nuclear antibodies as serologic markers in progressive systemic scleroderma]. AB - In all, 36 patients with progressive systemic sclerosis (29 women, 7 men) were studied clinically and immunologically; 15 patients had acrosclerosis (type I) and 21, sclerosis extending beyond the wrist (type II). The sera of all patients were evaluated for ANA (HEp-2-cells), Scl-70, centromere and other ENA antibodies. The centromere antigen was characterized by immunoblotting. All patients had high-titer ANA antibodies (100%); 36% of patients had the Scl-70 antibody (a marker antibody for PSS); and in 22% of our patients a centromere antibody was detected. In all cases the anti-centromere sera reacted with a 19.5 kd polypeptide and in 2 cases they reacted with 23- and 25.5-kd proteins in addition. In patients with centromere antibodies there was increased organ involvement (heart, lung, kidney) compared with patients who had anti-Scl-70 or other nuclear antibodies. PMID- 3106262 TI - Shielding design for the ceiling of a 6-MV accelerator in an existing facility. PMID- 3106263 TI - Sigmoid growth and the assessment of hormesis: a case for caution. AB - Recent advances in procedures for the analysis of sigmoid curves have provided some sensitive methods of detecting and evaluating hormesis in the growth responses of organisms exposed to a variety of stressors. Based on a reparameterized Richards process error model, these procedures allow the quantification and independent evaluation of the three major properties of a sigmoid growth curve: size: a measure of the asymptote approached by the growth process, rate: a measure of the approximate amount of time required to complete growth, and shape: a quantity which indicates the specific path or trajectory taken by the growth process to approach the asymptote within the time constraints of the growing period. When applied to growth data for cypress tree seedlings and two species of waterfowl exposed chronically to low levels of a variety of stressors, these analyses revealed that curve shape was more likely to change in response to stress than were either asymptotic size or growth rate. The types of changes observed suggested that growth size, rate and curve shape may respond independently and in some cases, in opposite directions. Thus, while one aspect of growth may change in a fashion suggestive of hormesis (e.g. larger asymptote or faster growth rate), other aspects of the same growth function may be changing in a way suggestive of a stress response. Thus, studies designed to reveal growth hormesis should be specific with respect to which particular mathematical model is chosen, as well as with respect to which aspect of the growth response is being considered. PMID- 3106264 TI - Influence on cell proliferation of background radiation or exposure to very low, chronic gamma radiation. AB - Investigations carried out on the protozoan Paramecium tetraurelia and the cyanobacteria Synechococcus lividus, which were shielded against background radiation or exposed to very low doses of gamma radiation, demonstrated that radiation can stimulate the proliferation of these two single-cell organisms. Radiation hormesis depends on internal factors (age of starting cells) and external factors (lighting conditions). The stimulatory effect occurred only in a limited range of doses and disappeared for dose rates higher than 50 mGy/y. PMID- 3106265 TI - Comments on HCFA hospital death rate statistical outliers. Health Care Financing Administration. AB - In March 1986, the Health Care Financing Administration (HCFA) released ten lists of death-rate "outlier" hospitals, one for all 1984 Medicare discharges and nine for specific DRGs. Recent Medicare hospital discharge abstracts have substantially undercounted in-hospital deaths, with large variations by state. Apart from the proportion of a hospital's cases in 80 DRGs, the predictive models had no measures of case severity based on diagnosis or procedure. Having DRG 123 (all deaths from acute myocardial infarction) as an independent variable in the all-death regression model probably accounted for much of its high r2. Inclusion of an independent variable for average length of stay (ALOS) favored hospitals in higher ALOS states by higher predicted death rates. Model bias also favored lower risk hospitals. Small numbers of predicted deaths for specific DRGs limited low volume hospitals on these outlier lists to those with high ratios of actual to predicted deaths. On six of the nine DRG-specific outlier lists, a total 1,222 hospitals had unfavorable residuals, while only 8 were favorable. Ten recommendations are given to increase reliability of future outcome analyses. PMID- 3106266 TI - Pew Memorial Trust policy synthesis: 2. Postretirement health benefits. AB - One-fourth of all those over 65 have some form of employer-provided retirement medical benefits. For these retirees and dependents, having this medical coverage may mean the difference between retirement security and ruin; but for employers, providing it could mean serious financial strain or even a threat to survival. The unfunded liability for retirement medical coverage has been variously projected from +100 billion to nearly +2 trillion. Continuing corporate concerns over the costs of health care, and recent changes in federal policies regarding Medicare and the taxation of employee benefit funds, threaten to alter the system of postretirement health benefits substantially and perhaps irrevocably for many. Employers are being forced to reassess their retiree commitments. Some corporations have undertaken to modify and even eliminate postretirement medical coverage for those over 65. These changes will affect not only the corporations involved and their retirees, but also the national and state governments to whom retirees may turn for additional assistance in meeting their health care needs. The purpose of this synthesis is to explain the issue of postretirement health benefits (PRHBs) for both public and private sector policymakers who will be most involved with this issue over the next five years. The analysis identifies the issues involved, considers the dimensions of the problem, and attempts to assess the implications for the future. PMID- 3106267 TI - Cost-sharing and the use of general medical physicians for outpatient mental health care. AB - Many patients with emotional disorders receive their mental health care from general medical physicians. In this article, we examine differences in costs and style between mental health care delivered by mental health specialists and that provided by general medical physicians, and the sensitivity to insurance of the patient's choice of mental health care provider. We use data from a randomized trial of cost-sharing, the RAND Health Insurance Experiment. Even when all outpatient mental health care was free (up to 52 visits a year), one-half of the users of outpatient mental health services visited general medical providers only. This half accounted for only 5 percent of outpatient mental health care expenditures, because the treatment delivered by general medical providers was much less intensive than that delivered by mental health specialists. Mental health status, at enrollment, was similar for those who received their mental health care from either provider group. Despite the large difference in cost of care, the choice of provider (mental health specialist versus general medical provider) was not sensitive to the generosity of insurance. PMID- 3106268 TI - Impact of long-term home care on hospital and nursing home use and cost. AB - This article reports the long-range impact of a long-term home care program in Chicago on hospital and nursing home use and on overall health care costs over four client-years of observation. The evaluation utilized a quasi-experimental design with a comparison group composed of clients who received home-delivered meals. The health services utilization experience of consecutively accepted treatment (N = 157) and comparison group (N = 156) subjects was monitored for 48 client-months following acceptance to care. Imputed costs were then assigned to each type of care measured. Findings include a significantly lower risk of permanent admission to sheltered and intermediate-level nursing home care in the treatment group but no difference in risk of permanent admission to skilled-level nursing home care. Despite savings in low-intensity nursing home days, preliminary findings indicate that total costs of care were 25 percent higher in the treatment group. However, these costs are accompanied by significant quality of-life benefits in the treatment group (reported elsewhere). PMID- 3106269 TI - Penicillin resistance of Pseudomonas aeruginosa clinical isolates from urinary tract infections. PMID- 3106271 TI - [Further development of pneumatization of the mastoid apophysis in long-term drainage of the tympanum]. AB - Tubal insufficiency evoked by inflammation or mechanical obstruction due to enlarged adenoids plays an important role in the pathogenesis of chronic serous otitis media. Serous and mucous tympanic effusions in the presence of immature middle ear mucosa and pneumatisation follow. An adhesive process can be the result. Secretory outflow as well as constant pressure compensation between the tympanic cavity and the auditory meatus can only be achieved by a long-term tympanic drainage. Progression of pneumatisation is achieved by recovery of the middle ear mucosa and in most cases an adhesive process can be prevented. PMID- 3106270 TI - Histochemical detection of alpha-D-glucosidases and their molecular forms with 5 Br-4-Cl-3-indoxyl-alpha-D-glucoside. AB - 5-Br-4-Cl-3-Indoxyl-alpha-D-gluco(pyrano)side was found to be the most suitable synthetic substrate for the demonstration of alpha-D-glucosidases in situ. Using an azoindoxyl procedure with hexazotized pararosaniline or new fuchsine at pH 5 in freeze-dried celloidine-mounted cryostat sections acid alpha-D-glucosidase (EC 3.2.1.20) was shown for the first time in lysosomes of many cells of fetal and adult rat, mouse, guinea-pig, marmoset and human organs. At pH 6.5, in chloroform acetone pretreated cryostat sections plasma membrane alpha-D-glucosidases were shown in the brush border of enterocytes of the small and large intestine, in the brush border of proximal renal tubule cells and in the stereocilia of the epididymal duct. In an indigogenic procedure with ferricyanide/ferrocyanide as redox catalysator plasma membrane alpha-D-glucosidases were depicted as well as with the azo-indoxyl method; the demonstration of the acid alpha-D-glucosidase was inferior to that achieved with the azo-indoxyl procedure. Using tetrazolium salts as capture reagent intracellular localization was unsatisfactory. In enterocytes, a localization in the Golgi apparatus was shown by the azo-indoxyl procedure only. Analytical isoelectric focusing revealed organ-dependent differences of plasma membrane and lysosomal alpha-D-glucosidases. Compared with the already existing methods the azo-indoxyl and indigogenic procedures are by far the most suitable techniques. PMID- 3106273 TI - Antibodies in calves on feed supplemented with chlortetracycline after vaccination with Brucella abortus strain 19. AB - Twenty dairy heifers each consumed 350 mg of chlortetracycline/day in their feed. Four tests were performed on serum specimens from these and 20 control calves after vaccination with Brucella abortus strain 19. The numbers of positive test results on the card test and mean titers on the tube and rivanol agglutination and complement-fixation tests were compared in the 2 groups. Using the rivanol and complement-fixation tests, there were differences in the mean titers at weeks 5 and 6 after vaccination, but by week 10, differences were not found. The results suggest that addition of low concentration of chlortetracycline in feeds have minimal effects on postvaccinal serologic reactions determined after strain 19 inoculation. PMID- 3106274 TI - Arterial blood gas tensions in the horse during recovery from anesthesia. AB - The effects of body position and postoperative oxygen supplementation on arterial blood gas tensions (PaO2 and PaCO2) and pH were examined in clinically normal adult horses during recovery from halothane anesthesia. Hypoxemia developed during recovery from anesthesia in spite of adequate alveolar ventilation in horses without postanesthetic oxygen supplementation. Hypoxemia developed in horses positioned in left lateral or right lateral recumbency, and in horses that were rolled to the opposite side during the recovery period. Arterial blood gas tensions were not significantly (P greater than 0.05) different between horses insufflated with 100% oxygen at the rate of 10 L/min during recovery and horses that did not receive oxygen supplementation during the recovery period. Horses that received 100% oxygen at the rate of 50 L/min through a demand valve had arterial blood gas tensions similar to those in standing awake horses. PMID- 3106272 TI - Repair of sublethal radiation injury after multiple small doses in mouse kidney: an estimate of flexure dose. AB - Functional kidney damage in mice was measured after a series of fractionated X irradiations. Doses per fraction of 0.75-12.5 Gy were given as 2, 5, 10, 30, 40, 60, or 80 equal doses in a total treatment time of 4 weeks. Renal function (measured by clearance of 51CrEDTA or hematocrit levels) deteriorated progressively, in a dose related manner, from 20 to 46 weeks after the start of treatment. The changes in renal function versus time were fitted by a polynomial regression through all data and interpolated values for 51CrEDTA clearance were then calculated at 30 and 40 weeks after treatment. Steep dose response curves were obtained and these were used to calculate isoeffective doses for the different fractionation schedules. There was a marked increase in total isoeffective doses from 2-30 fractions and these data were well described by a linear quadratic (L.Q.) expression for damage with an alpha/beta ratio of 2.3 +/- 0.2 Gy. There was only a slight increase in the total isoeffect dose as the size of the dose per fraction was decreased below 2 Gy and the measured isoeffect doses after 40 to 80 fractions were lower than predicted on the basis of an L.Q. model assuming complete repair between successive irradiations. The flexure dose for mouse kidneys irradiated 3 times per day was, effectively, 1 to 2 Gy and hyperfractionation using lower doses per fraction did not lead to significant, additional repair. PMID- 3106275 TI - The problem of smoking and lung cancer in Japan with special reference to the rising trend in age-specific mortality rate by number of cigarettes smoked daily. PMID- 3106276 TI - Transforming activity of human c-Ha-ras-1 proto-oncogene generated by the binding of 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole and 4-nitroquinoline N oxide: direct evidence of cellular transformation by chemically modified DNA. AB - An activity that transforms NIH 3T3 cells was generated by the in vitro modification of plasmids containing the human c-Ha-ras-1 proto-oncogene with the synthesized ultimate carcinogen, 2-acetoxyamino-6-methyldipyrido[1,2-a:3',2'-d] imidazole (N-OAc-Glu-P-1). DNAs isolated from the transformed cells were analyzed by restriction fragment length polymorphism (RFLP) assay using the restriction enzyme Msp I. Of fourteen transformants studied, six contained a mutation in the region of the CCGG sequence of the eleventh and the twelfth codons, in which GG corresponds to the first two nucleotides of the twelfth codon. Transforming activity was also generated by the chemical modification of the plasmids with 4 acetoxyaminoquinoline N-oxide (N-OAc-4AQO). The results clearly indicate that formation of DNA adducts with N-OAc-Glu-P-1 or N-OAc-4AQO causes the induction of transformation of mammalian cells. PMID- 3106277 TI - A factor inducing differentiation of the human monocytic cell line U-937 produced by 12-O-tetradecanoylphorbol 13-acetate-treated U-937. AB - A new factor capable of inducing differentiation of human leukemic cell line U 937 into macrophages was found and partially purified from the conditioned medium of U-937 previously treated with 12-O-tetradecanoylphorbol 13-acetate. The purification procedure included ultrafiltration, DEAE-Sephacel and butyl Toyopearl column chromatography. The purified factor gave a major band of protein with a molecular weight of 67,000 daltons which coincided with the biological activity of differentiation-inducing factor, and it was not adsorbed on a concanavalin A column. These results suggest that this factor is distinct from other differentiation-inducing factors. PMID- 3106278 TI - Presence of tumor promoters in the seed oil of Jatropha curcas L. from Thailand. AB - The seed oil of Jatropha curcas L. was shown to contain skin tumor promoters in a two-stage mouse carcinogenesis experiment. By using the irritant test on mouse ear to monitor activity, the "irritant fraction" was partially purified from the methanol extract of the seed oil by column chromatographies on Florisil and Sephadex LH-20. The irritant fraction obtained induced ornithine decarboxylase in mouse skin and inhibited the specific binding of 3H-12-O-tetradecanoylphorbol-13 acetate to a particulate fraction of mouse skin. After initiation with 7,12 dimethylbenz[a]anthracene (DMBA), this "irritant fraction" induced tumors in the skin of 36% of the mice tested in 30 weeks. Tumor incidences in the groups treated with DMBA alone and "irritant fraction" alone were 7% and 13% in week 30, respectively. Since the skin of Thai people comes into direct contact with this seed oil, an epidemiological study on human skin cancer in Thailand is indicated. PMID- 3106279 TI - Characterization of three monoclonal antibodies (VAK3-5) that identify p24, core protein of human immunodeficiency virus, and its precursors. AB - VAK3, VAK4 and VAK5 monoclonal antibodies (mAbs) were raised by using disrupted purified human immunodeficiency virus (HIV) as an antigen. These mAbs exclusively reacted with an HIV-infected cell line, H9/HIV, and did not react with human T cell lymphotropic virus (HTLV)-I or -II infected cell lines. Strip radioimmunoassay based on the Western blotting technique revealed that these mAbs recognize a single band that corresponds to a 24-kd (p24) core protein of HIV when disrupted viruses were used as antigens. When cell lysates of H9/HIV were used as antigens, these mAbs gave two bands with molecular weights of 40 kd (p40) and 57 kd (p57) in addition to p24. VAK5-conjugated Sepharose 4B beads precipitated non-glycosylated proteins, p24, p40 and p57 from [L-35S]methionine labeled H9/HIV. P57 and p40 appear to be a precursor and an intermediate precursor of p24, respectively. Purified IgG of VAK3 and VAK4, and the serum from an individual infected with HIV inhibited the binding of VAK5 mAb to HIV. These findings suggest that p24 of HIV contains structure(s) with strong antigenicity. PMID- 3106280 TI - Non-simultaneous primary cancers in five different organs in a case of cancer family syndrome. AB - Non-simultaneous primary malignant tumors in five different organs were detected in a case of cancer family syndrome, and the patient's offspring were found to have colorectal cancers during follow-up. The first cancer in the patient was found in the transverse colon at the age of 47, and partial colectomy was carried out. The second and third were cancers of the cecum and gallbladder which were found concurrently at the age of 61, and ileocecal resection and cholecystectomy were carried out simultaneously. The fourth was cancer of the urinary bladder which was found at the age of 66, and partial cystectomy with interstitial irradiation using a radon seed in the residual urinary bladder was carried out. The fifth was cancer of the stomach at the age of 72, and subtotal gastrectomy was carried out. All of the resected specimens were demonstrated to be different carcinomas histologically. The father and 5 of the 7 siblings of this patient suffered from gastrointestinal or uterine cancers. Furthermore, two daughters of this patient were affected with cancer; the younger with cancer of the descending colon at the age of 47, and the elder with cancers of the transverse colon and rectum at the age of 54. Thus, familial clustering of cancer was shown. Genetic characteristics may have contributed to the development of multiple primary cancers in this family. PMID- 3106281 TI - Specific expression of unusual GM2 ganglioside with Hanganutziu-Deicher antigen activity on human colon cancers. AB - This paper reports the presence of GM2 ganglioside containing N glycolylneuraminic acid (NeuGc) in human colon cancer tissues. GM2(NeuGc) was detected by two-dimensional thin layer chromatography (2d-TLC)/enzyme immunostaining using affinity-purified chicken antibody against GM3(NeuGc) and horseradish peroxidase-conjugated rabbit anti-chicken IgG antibody. Like usual GM2 ganglioside containing N-acetylneuraminic acid (NeuAc) isolated from Tay Sachs brain, GM2(NeuGc) in colon cancer could be converted into GM3(NeuGc) by human kidney beta-N-acetylhexosaminidase A in the presence of a GM2-specific activator protein isolated from guinea pig kidney. Three of 7 specimens of Hanganutziu-Deicher (HD) antigen-positive human colon cancer tissues so far examined expressed this unique ganglioside. In order to detect and determine specifically GM2(NeuGc) on human colon cancers, specific antibody against GM2 (NeuGc) has been prepared by immunizing chickens. By a sensitive TLC/immunostaining method using the antibody, the amounts of the antigen were determined to be 0.3-3% of total lipid-bound sialic acid. NeuGc-containing gangliosides were also detected in meconium and fetal intestinal tissues. Three species of antigenic gangliosides in pooled meconium were tentatively identified as GM3(NeuGc), sialylparagloboside and sialylhexaosylceramide on the basis of their migration positions on 2d-TLC and the results of endo-beta-galactosidase treatment. GM3(NeuGc) was the sole HD-active ganglioside in fetal intestinal tissue from one of 3 individuals tested; the other two showed no HD-active ganglioside at all. GM2(NeuGc), however, could not be detected in either meconium or fetal tissues so far examined, suggesting that this unique ganglioside is a tumor-specific antigen, at least for human intestinal tissues. PMID- 3106282 TI - Dysfunction of Ia-positive antigen-presenting cells in tumor-bearing mice. AB - The activities of T cells and antigen-presenting cells in spleen from tumor bearing mice were studied in vitro. The in vitro induction of trinitrophenyl (TNP)-specific proliferative T cell responses and TNP-specific cytotoxic T cell responses was markedly impaired in spleen cells from X5563 plasmacytoma-bearing C3H/He mice. The activity of TNP-hapten presentation to proliferative T cells and cytotoxic T cells was also impaired in spleen from tumor-bearing mice. Suppressor macrophage activity was not observed in spleen from tumor-bearing mice, because the addition of TNP-modified spleen cells from tumor-bearing mice to TNP-modified spleen cells from normal mice did not suppress the activity of TNP-hapten presenting cells from normal mice and the addition of indomethacin, an inhibitor of prostaglandin synthesis, to the culture of T cells with TNP-modified spleen cells from tumor-bearing mice did not restore their activity. The population of I region associated antigen (Ia)-positive cells in spleen macrophages decreased in tumor-bearing mice. Furthermore, the production of interleukin 1 by spleen macrophages was also impaired in tumor-bearing mice. These results suggest that one of the mechanisms leading to immunological abnormality in the tumor-bearing host is mediated by the dysfunction of Ia-positive antigen-presenting cells. PMID- 3106283 TI - Restoration of impaired T cell functions in tumor-bearing mice by the administration of interleukin 1. AB - The effect of in vivo administration of recombinant human interleukin 1 (IL-1) on T cell functions in tumor-bearing mice was studied using an in vitro assay system. The in vitro induction of trinitrophenyl (TNP)-specific cytotoxic T cell and proliferative T cells responses from spleen cells was impaired in X5563 plasmacytoma-bearing C3H/He mice. However, the administration of IL-1 alpha or IL 1 beta to tumor-bearing mice restored T cell functions in a dose-dependent manner. Antigen-presenting activities of spleen cells in tumor-bearing mice for T cell activation were not restored by the administration of IL-1. The activities of cytotoxic T cells and cytostatic T cells specific for X5563 cells were also enhanced by the administration of IL-1. Furthermore, in IL-1-treated mice, NK cell activity of spleen cells detected in terms of the killing of Yac-1 cells was also restored. In accordance with these results, the growth of X5563 cells was significantly inhibited and the lymphocytes from IL-1-treated mice specifically inhibited the growth of tumor cells. These results suggest that the in vivo administration of IL-1 restored the impaired T cell and NK cell functions in tumor-bearing mice and activated protective immunity against tumor cells. Thus, recombinant IL-1 can be applied for tumor immunotherapy. PMID- 3106285 TI - Human alveolar macrophages: wheat germ agglutinin-dependent tumor cell killing. AB - Human alveolar macrophages (AM) obtained by bronchoalveolar lavage from healthy donors were examined for ability to cause lectin-dependent tumor cell killing. Of five plant and two animal lectins tested, only one lectin, wheat germ agglutinin (WGA), induced significant and reproducible lectin-dependent macrophage-mediated cytotoxicity (LDMC) against human bladder cancer (T-24) cells. There was no significant difference between the LDMCs of AM and blood monocytes. All 6 tumor cell lines tested were sensitive to various extents to LDMC induced by WGA. Quantitative analysis with WGA-FITC conjugate showed the presence of various levels of receptors for WGA on the surface of AM, monocytes and tumors. A relatively good correlation was found between the sensitivities of the tumor cells to LDMC mediated by AM and the numbers of receptors for WGA. Pretreatment of AM or monocytes with LPS did not affect their LDMC. These results indicate that a plant lectin, WGA which binds to both human AM and tumor cells, renders human AM cytotoxic to allogeneic tumor cells by a different mechanism(s) from that involved in the nonspecific tumor cytotoxicity of activated macrophages. PMID- 3106284 TI - Restoration of lipopolysaccharide-mediated cytotoxic macrophage induction in C3H/HeJ mice by interferon-gamma or a calcium ionophore. AB - Proteose peptone-induced peritoneal exudate macrophages (PEM) from C3H/HeJ mice do not respond to lipopolysaccharide (LPS) in vitro in terms of activation for tumor cytotoxicity. This unresponsiveness of PEM was overcome by addition of culture supernatant of normal mouse spleen cells stimulated with insoluble concanavalin A. The supernatant component responsible for the restoration of PEM sensitivity to LPS was indicated to be interferon (IFN)-gamma, because pretreatment of the supernatant with anti-mouse IFN-gamma antiserum, but not with anti-IFN-(alpha + beta) antiserum, abolished the supernatant activity and because recombinant murine IFN-gamma (rIFN-gamma) could replace the supernatant effect. Not only the LPS activation of tumor cytotoxicity of PEM but also the sensitivity of PEM to the lethal toxicity of LPS was restored by rIFN-gamma. IFN-gamma action in restoring the LPS responsiveness of PEM was mimicked by a calcium ionophore, A23187, but not by phorbol 12-myristate 13-acetate. These results suggest that IFN-gamma can restore LPS responsiveness of PEM from C3H/HeJ mice and that elevation of the intracellular calcium level is involved in the action of IFN gamma. PMID- 3106286 TI - Studies on beta-lactam antibiotics. I. Synthesis and in vitro anti-pseudomonal activity of 3-isothiazole-cephalosporin derivatives. AB - The synthesis and in vitro activity of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(2 carboxy-2- alkoxyimino)acetamido]cephalosporins with a (4-carboxy-3-hydroxy-5 isothiazolyl)thiomethyl group at the 3-position are described. These cephalosporins (9a approximately 9i) showed excellent activity against Gram negative bacteria including beta-lactamase producing strains. The most interesting compound of the series was 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2- (2 carboxy-2-propoxyimino)acetamido]-3-cephem-4-carboxylic acid (9g, YM-13115) because of its outstanding inhibitory potency against Pseudomonas aeruginosa and highly prolonged plasma half-life in rats. PMID- 3106287 TI - Effect of amino acids on the biosynthesis of beta-amino acids, constituents of bacillomycins F. PMID- 3106288 TI - A novel polyether antibiotic, AC7230 (3-hydroxycezomycin or its stereoisomer). PMID- 3106289 TI - The aurachins, new quinoline antibiotics from myxobacteria: production, physico chemical and biological properties. AB - The aurachins, new quinoline alkaloids, were extracted with acetone from the biomass of the myxobacterium, Stigmatella aurantiaca strain Sg a15 and purified by column chromatography. The four described aurachins A, B, C and D, were inhibitory for Gram-positive bacteria and a few yeasts and molds. They blocked NADH oxidation in beef heart submitochondrial particles. PMID- 3106290 TI - The effect of kazusamycin on the growth of murine solid tumors and their spontaneous metastasis. PMID- 3106291 TI - Prostaglandins in the semicircular canal of the frog. AB - The synthesis of prostaglandins by ampulla and duct tissue isolated from the frog posterior semicircular canal was investigated in vitro. Ampulla and duct produced PGE2 (9 and 6 pg/structure, respectively) and prostacyclin (26 and 12 pg/structure). In the ampulla, prostaglandins mostly originated from the part containing dark and sensory cells and was not altered by 10(-3) M streptomycin. Prostaglandin levels were time-dependent and temperature-dependent. Arachidonic acid (3 X 10(-5) M) stimulated PGI2 synthesis by ampulla and duct (by 11.4 and 17 times) and PGE2 synthesis by 50 times in both structures. Ionophore A23187 stimulated ampulla and duct PGI2 synthesis (by 4.8 and 5.6 times) and PGE2 synthesis (by 2.4 and 1.8 times). Subcutaneous 100 mg/kg aspirin reduced PGI2 and PGE2 synthesis (ampulla: -87%, -33%; duct: -100%, -33%). Indomethacin (10(-6) M), in vitro, decreased PGI2 and PGE2 synthesis (ampulla: -47%, -47%; duct; -22%, 77%). Within 3 h, aspirin (5 X 10(-6) M) or arachidonic acid (2 X 10(-5) M) did not change Na and K concentrations in endolymph. It is concluded that frog inner ear produces PGI2 and PGE2, mostly from the part containing the dark cells, and that prostaglandins could be involved in the physiology of inner ear. PMID- 3106292 TI - Pituitary responsiveness of mares challenged with GnRH at various stages of the transition into the breeding season. AB - Four groups of mares, representing anestrus (AN; n = 8), early transition (ET; n = 7), late transition (LT; n = 8) and estrus (EST; n = 12) were used to examine release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) after a bolus injection of gonadotropin releasing hormone (GnRH) during the transition from anestrus into the breeding season. Estrous mares received GnRH on d 2 or 3 of estrus in the cycle immediately preceding slaughter. Anestrous, ET and LT mares received GnRH exactly 1 wk prior to slaughter. A single injection of GnRH (Sigma LHRH, L-0507, 2.0 micrograms/kg body weight in .9% saline, iv) was given to each mare. Blood samples were collected at -2, h, -1 h, directly prior to GnRH, then 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, 360, 420 and 480 min post-injection. Maximum release of LH and FSH was observed within 30 min after injection of GnRH. Except for the LH response in EST mares, concentrations of both hormones had returned to pre-injection baseline levels within 8 h. Group means for area under the curve (AUC) of concentrations of LH in serum, and the maximum amount (MAX) of LH quantified in serum, post-GnRH, increased (P less than .05) progressively from AN to the breeding season. The AUC and MAX responses for FSH showed a reverse pattern, decreasing (P less than .05) from AN to the breeding season.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106293 TI - Passive immunization of cyclic mares against androgen: gonadotropin and progesterone concentrations and estrous characteristics. AB - Antiserum generated in a horse against testosterone conjugated to bovine serum albumin (BSA) was administered to six lighthorse mares (androgen-immunized mares) 1 to 3 d before a prostaglandin-induced estrus and twice again at 2-d intervals. Six control mares were administered antiserum generated against BSA on the same schedule. Relative to testosterone, cross-reactivities of other steroids with the testosterone antiserum were (%): dihydrotestosterone, 52; 5 alpha-androstane-3 alpha,17 beta-diol, 8.6; androst-4-ene-3,17-dione, 1.2; and all others tested less than .1. Tritiated testosterone binding in plasma increased (P less than .01) in androgen-immunized mares within 1 h and remained elevated (P less than .01) relative to controls for greater than 21 d. There was no effect (P greater than .10) of passive immunization against androgen on interval to estrus after prostaglandin injection, duration of estrus, ovarian volume, number of palpable follicles or follicular volume during estrus. In contrast, concentrations of luteinizing hormone (LH) were higher (P less than .05) in androgen-immunized mares than in control mares during estrus and early diestrus. Concentrations of follicle stimulating hormone (FSH) and progesterone at those times were not affected (P greater than .10). From these data, we conclude that androgens in the mare during estrus may be involved with the regulation of LH secretion. In contrast, no involvement with FSH secretion was apparent under these short-term conditions. PMID- 3106294 TI - Effect of charcoal-extracted porcine follicular fluid and 17 beta-estradiol on follicular growth and plasma gonadotropins in gilts fed a progesterone agonist, altrenogest. AB - Thirty-four gilts in two experiments were fed altrenogest for 18 d to block spontaneous growth of ovulatory follicles after luteolysis. They were injected with estradiol or charcoal-extracted porcine follicular fluid (pFF) to determine 1) whether gonadotropin secretion could be depressed and 2) whether exposure to reduced levels of gonadotropins would result in decreased numbers of medium follicles (3 to 6 mm in diameter). Gilts in Exp. 1 received treatments in a 2 X 2 X 2 factorial arrangement starting 48 h before the last feeding of altrenogest. Corn oil or estradiol (2 micrograms/kg body weight), 5 ml of charcoal-extracted porcine serum (pS) or pFF were injected im four times at 8-h intervals and gilts were sacrificed 24 or 96 h after last feeding of altrenogest. In Exp. 2, gilts received one of four treatments consisting of 1) pS, injected iv nine times at 8 h intervals starting 48 h before the last feeding of altrenogest; 2) pFF, with injection protocol the same as for pS; 3) estradiol injected im three times and 4) four times at 8-h intervals starting 0 and 24 h, respectively, before the last feeding of altrenogest. Compared with pS or corn oil, estradiol increased (P less than .001) plasma estrogen and decreased (P less than .05) plasma luteinizing hormone (LH) without a significant effect on plasma follicle stimulating hormone (FSH). Estradiol, compared with corn oil, decreased (P less than .01) the number of medium follicles from 24.8 to 0/gilt and decreased (P less than .05) the weight of ovarian follicular fluid from 4.2 to 2.1 g/gilt at 72 h after the first injection. Five milliliters of pFF had no significant effect on plasma gonadotropins or number of medium follicles. However, 20 ml of pFF, compared with pS, decreased (P less than .05) plasma FSH from 45 ng/ml to 9 ng/ml 32 h after the first injection, had no effect on plasma LH, decreased (P less than .01) the number of medium follicles from 29.2 to 2.2/gilt and decreased (P less than .01) follicular fluid weight from 3.9 to 1.6 g/gilt by 72 h after the first injection. These results indicate that estradiol or a non-steroidal component of follicular origin can decrease secretion of gonadotropins and suppress recruitment of medium follicles in the pig. PMID- 3106295 TI - Plasma somatotropin response to exogenous growth hormone releasing factor in lambs. AB - Two experiments were performed to examine the ability of human pancreatic growth hormone releasing factor (hGRF) administration to stimulate endogenous growth hormone (GH) secretion in lambs. Each study utilized eight Dorset wether lambs in replicated 4 X 4 Latin square experiments. Growth hormone response (integrated area under the curve for 150 min post-injection) for 0, 1, 5 and 10 micrograms hGRF/kg body weight averaged 13, 23, 92 and 134 units, respectively. While the 1 microgram hGRF dose was not different (P greater than .05) than the response to saline injection, there was an increased (P less than .01) GH response to 5 or 10 micrograms hGRF. Overall the GH response increased in a log dose-response fashion. There was distinct variation between lambs in their response to hGRF. Study II examined the optimal method to administer 40 micrograms hGRF/kg body weight to maximize GH concentration over 24 h. Continuous infusion (CI) was compared with eight (8X), four (4X), or two (2X) injections/d. Hourly blood samples were obtained from all lambs. Growth hormone response (area under the curve for 24 h) was 162, 305, 306 and 220 units for CI, 8X, 4X and 2X, respectively. Growth hormone response to CI was inferior to discrete injections, and the GH response to 4X or 8X was superior to 2X/d. Results demonstrate that, in spite of lamb-to-lamb variation, one can utilize exogenous hGRF to enhance GH secretion in lambs. Thus, the ability of exogenous hGRF to enhance growth performance merits further study. PMID- 3106296 TI - Tryptophan and threonine requirements of young pigs and their effects on serum calcium, phosphorus and zinc concentrations. AB - Four 28-d trials were conducted using a total of 432 pigs, with average initial weight across trials ranging from 6.3 to 9.7 kg, to estimate the tryptophan (trials 1 and 2) and threonine (trials 3 and 4) requirements of pigs fed low protein, corn-sunflower meal diets. The effect of tryptophan, threonine and protein level on serum calcium, phosphorus and zinc also was studied. The diets contained either 12 or 13% protein and were calculated to be adequate in all nutrients except crude protein and the amino acid being investigated. A lysine supplemented, 18% protein, corn-sunflower meal diet was included in all trials as a positive control. In trial 1, weight gains of pigs increased linearly (P less than .005) while feed conversion improved cubically (P less than .05) as dietary tryptophan increased from .14 to .22%. Pigs fed the 18% protein diet gained faster (P less than .05) and required less feed/gain than pigs fed low protein diets. In trial 2, weight gains improved quadratically (P less than .005) and feed conversion improved linearly (P less than .05) as dietary tryptophan increased from .104 to .204%. Serum phosphorus and zinc concentrations were lower (P less than .05) in pigs fed the 18% protein diet. In both trials, serum urea N responded quadratically (P less than .05) to increasing dietary tryptophan, and was lower (P less than .05) in pigs that were fed diets supplemented with L tryptophan than in those fed the low protein basal or 18% protein diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106297 TI - Hormonal patterns of boars exposed to natural or supplemental lighting during pubertal development. AB - Thirty-two crossbred boars (Hampshire X Duroc X Yorkshire) were reared under natural lighting (35 lx) or supplemental lighting (1,400 lx) beginning at 4 wk of age. Boars received supplemental lighting from six 40-W fluorescent bulbs between 0530 and 2030 in a nursery unit. From 9 to 32 wk of age, boars received either natural lighting (30 lx) or supplemental lighting (100 lx) in a growing-finishing unit. Blood samples were collected from indwelling cannulae at 20-min intervals for 6 h every 2 wk from 2.5 to 7 mo of age. Libido scores were evaluated during alternate weeks when intensive blood samples were not taken. Libido scores were not different between natural and supplemental lighting treatments (P greater than .30). However, at 122 d of age, libido scores of boars exposed to supplemental lighting tended to be higher (P = .10) than those exposed to natural lighting. Although mean serum concentrations of luteinizing hormone (LH) were higher (P less than .05) in boars at 75, 89, 103 and 131 d of age reared under supplemental lighting than boars of the same age reared under natural lighting, the number of LH secretory spikes was similar between the treatment groups (P = .39). Serum concentrations of LH decreased in both treatment groups as boars became older (P less than .05). However, the incidence of LH spikes was similar across ages and between treatment groups from 2.5 to 7 mo of age. Mean serum concentrations of follicle stimulating hormone and testosterone were similar between treatments (P greater than .75). PMID- 3106298 TI - The effect of nitrogen and carbon sources on proteinase production by Pseudomonas fluorescens. AB - Some factors influencing the production of an extracellular proteinase by Pseudomonas fluorescens NCDO 2085 were studied. Proteinase production was optimal at 20 degrees C and pH 6.9 in static culture when calcium was included in the medium. Proteinase was not detectable in basal medium but could be induced by organic nitrogen compounds. The proteinase was produced in the exponential phase of growth on protein substrates but not until early stationary phase during growth on amino acids. The organism did not utilize lactose, the most abundant carbohydrate in milk. Citrate was readily utilized as an energy source but had a strong repressive effect on proteinase production. A medium containing sodium caseinate and pyruvate supported good growth and enzyme production. All the amino acids utilized as a sole carbon source, with the exception of serine, could induce proteinase production. Asparagine was the most effective amino acid inducer. Particular combinations of amino acids could induce or repress proteinase production. The regulation of proteinase production by Ps. fluorescens NCDO 2085 appears to be based on a balance between induction by low concentrations of low molecular weight degradation products and sensitivity to end product catabolite repression. The results suggest that the function of the proteinase is to ensure a supply of carbon rather than amino acids for protein synthesis. PMID- 3106300 TI - In-vitro susceptibility of Pseudomonas species to fifteen antimicrobial agents. AB - The in-vitro susceptibility of four Pseudomonas spp. (P. aeruginosa, P. fluorescens, P. maltophilia and P. putida) to 15 antimicrobials was determined. Ciprofloxacin had the greatest in-vitro activity. Although the susceptibility of the different species to individual agents was quite variable, they tended to be less susceptible to agents such as amikacin, aztreonam, cefoperazone, ceftazidime and piperacillin, already in clinical use at our institution, than to newer agents, not currently in clinical use. PMID- 3106299 TI - The cutaneous microbiology of normal human feet. AB - A survey has been made of the bacterial and fungal populations carried at three different sites on the feet of 60 individuals. The bacteria found at the three sites were quantitatively similar and Micrococcaceae and aerobic coryneform bacteria predominated. The carriage of other bacterial groups was generally low. There was a quantitative variation between sites--mean total counts were 1.04 X 10(7) cfu/cm2 skin in the fourth toe cleft, 4.08 X 10(5) cfu/cm2 skin on the sole and 1.21 X 10(3) cfu/cm2 skin on the dorsal surface. Staphylococci were most often dominant on the sole and dorsal surface whereas aerobic coryneforms predominated in the majority of fourth toe clefts. The higher the total count at a given site the more likely it was that aerobic coryneform bacteria predominated. The skin surface pH was significantly higher on the sole (mean value 6.25) than on the dorsal surface (mean value 5.23). Factors controlling the microbial ecology of the foot are discussed. PMID- 3106301 TI - Dynamics of ceftazidime-pefloxacin interaction shown by a new killing curve chequerboard method. AB - Since in-vitro methods for studying drug interactions are difficult to evaluate and different results occur with the chequerboard (isobolograms-FIC index) and killing curve methods, a new approach associating these two methods was used to study the ceftazidime-pefloxacin interaction. In 64 tubes in a chequerboard pattern, viable bacteria were counted at 0, 2.5, 5 and 24 h, by a microdilution method and a multiple inoculator replicating method. The bacterial inoculum consisted of 5 X 10(6)-10(7) cfu/ml. Twelve strains belonging to six genera were tested: Acinetobacter, Citrobacter, Enterobacter, Klebsiella, Serratia and Pseudomonas. During the first 5 h no antagonism was noted, but few differences in viable count equal to or greater than 2 log10 were observed. The results of the drug interaction were equivalent to those of the more rapid bactericidal antibiotic concentrations (ceftazidime or pefloxacin). At 24 h, synergy was observed: ceftazidime prevented the late regrowth noted with pefloxacin, but with Citrobacter spp. regrowth was also observed with ceftazidime and none of the combinations were bactericidal. PMID- 3106302 TI - Rapid and automated measurement of Km and specific Vmax values of beta-lactamases in bacterial extracts. AB - A method is reported for automating measurements of Km and specific Vmax values from single progress curves of hydrolysis of beta-lactam antibiotics by crude (or purified) beta-lactamase preparations. The method is based on the half-time analysis procedure of Wharton & Szawelski (1982). The specific Vmax is obtained in units of mols of substrate hydrolysed /min/mg dry wt of cells, but could be expressed as easily in terms of mols of enzyme or mg of protein. We propose that the method will allow reporting of Km and specific Vmax values, rather than relative rates of hydrolysis, in surveys of bacterial beta-lactamases. PMID- 3106303 TI - Susceptibility of Rickettsia conorii and R. rickettsii to pefloxacin, in vitro and in ovo. AB - The activity of pefloxacin against Rickettsia conorii and R. rickettsii was determined by several methods. The mean survival time of embryonated eggs infected with R. conorii was increased by pefloxacin 50 micrograms/egg; plaque formation in Vero cells was inhibited by 1 mg/l. In a microplate assay, the MIC of pefloxacin was 0.5 mg/l for R. conorii and 1 mg/l for R. rickettsii. The results support the use of pefloxacin in treating spotted fever rickettsioses. PMID- 3106304 TI - In-vitro bacterial killing kinetics of ticarcillin/clavulanic acid. AB - An in-vitro model was developed to study the rates of killing by ticarcillin/clavulanic acid combinations of various beta-lactamase producing, ticarcillin resistant, logarithmic phase clinical isolates. Killing, defined as a 3 log reduction, was dependent on the organism, the concentration of clavulanic acid and the duration of exposure. For most isolates studied an optimum period of exposure to and concentration of clavulanic acid could be defined. Certain test strains showed optimum response to readily attainable in-vivo concentrations of clavulanic acid while other strains, although sensitive by MIC data showed a poor response. The clinical implications of this are discussed. PMID- 3106305 TI - Comparison of the activity of antibiotic combinations in vitro with clinical outcome and resistance emergence in serious infection by Pseudomonas aeruginosa in non-neutropenic patients. AB - Techniques for demonstrating synergy in vitro were compared in testing different beta-lactam-aminoglycoside combinations against 30 isolates of Pseudomonas aeruginosa. Poor concordance was noted among the results from chequerboard and 6 h and 24 h time-kill methods. Comparison of in-vitro synergy results with clinical outcome in 14 patients with pseudomonas infection showed that antagonism in the 24 h time-kill method was the most reliable prognostic indicator of clinical and bacteriological outcome. Although more than 70% of patients were cured clinically with cefsulodin or ticarcillin with tobramycin or amikacin, pseudomonas resistant to the beta-lactam emerged in 7 of 14 patients (50%); of those seven, three had poor clinical outcome. The rationale of adding aminoglycoside to beta-lactams against P. aeruginosa to prevent emergence of resistance needs closer examination. PMID- 3106306 TI - Induction of the beta-lactamases of a strain of Pseudomonas aeruginosa, Morganella morganii and Enterobacter cloacae. PMID- 3106307 TI - Role of carotid chemoreceptors and pulmonary vagal afferents during helium-oxygen breathing in ponies. AB - Our purpose was to assess compensatory breathing responses to airway resistance unloading in ponies. We hypothesized that the carotid bodies and hilar nerve afferents, respectively, sense chemical and mechanical changes caused by unloading, hence carotid body-denervated (CBD) and hilar nerve-denervated ponies (HND) might demonstrate greater ventilatory responses when decreasing resistance. At rest and during treadmill exercise, resistance was transiently reduced approximately 40% in five normal, seven CBD, and five HND ponies by breathing gas of 79% He-21% O2 (He-O2). In all groups at rest, He-O2 breathing did not consistently change ventilation (VE), breathing frequency (f), tidal volume (VT), or arterial PCO2 (PaCO2) from room air-breathing levels. During treadmill exercise at 1.8 mph-5% grade in normal and HND ponies, He-O2 breathing did not change PaCO2 but at moderate (6 mph-5% grade), and heavy (8 mph-8% grade) work loads, absolute PaCO2 tended to decrease by 1 min of resistance unloading. delta PaCO2 calculated as room air minus He-O2 breathing levels at 1 min demonstrated significant changes in PaCO2 during exercise resistance unloading (P less than 0.05). No difference between normal and HND ponies was found in exercise delta PaCO2 responses (P greater than 0.10); however, in CBD ponies, the delta PaCO2 during unloading was greater at any given work load (P less than 0.05), suggesting finer regulation of PaCO2 in ponies with intact carotid bodies. During heavy exercise VE and f increased during He-O2 breathing in all three groups of ponies (P less than 0.05), although there were no significant differences between groups (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106308 TI - Effects of prostaglandin F2 alpha and prostacyclin on pulmonary microcirculation in the cat. AB - In pulmonary microcirculation, using a new X-ray television system, we measured the effects of prostaglandin F2 alpha (PGF2 alpha) and prostacyclin on the internal diameter (ID), flow velocity, volume flow, and transit times of a contrast medium in small arteries (Ta) and veins (Tv) in anesthetized cats. The ID of the arteries and veins ranged from 100 to 500 micron. PGF2 alpha, 0.3, 1, and 3 micrograms/kg, predominantly decreased ID on the arterial side in a dose dependent manner but increased flow velocity 27-62%. Consequently, volume flow was kept relatively constant. With PGF2 alpha, Ta and Tv were decreased 18-41% and 4-15%, respectively. Prostacyclin, 2 and 4 micrograms/kg, uniformly dilated the ID of small arteries 9-16% but did not change small veins. With prostacyclin, flow velocity was unchanged or decreased, whereas volume flow was increased significantly, 27-32%. No significant changes of Ta and Tv were observed in response to prostacyclin. When both prostaglandins, PGF2 alpha and prostacyclin, were administered, they canceled each other with respect to the ID of small pulmonary arteries. Prostacyclin also prevented the PGF2 alpha-induced vasoconstriction of the pulmonary venous microcirculation. PMID- 3106310 TI - Use of a random forcing for high-frequency ventilation. AB - Previous applications of high-frequency oscillatory ventilation (HFOV) have used cyclic forcings with the frequency of oscillation considered to be a fundamental parameter. A question that is addressed in the present study is whether or not periodicity is an essential requirement for this mode of ventilation to occur. It was found possible to adequately ventilate anesthetized and paralyzed cats with volume excursions below the dead-space level using a random band-limited forcing. Experimental conditions were close to a constant flow variance (VARF) state, and arterial CO2 tension varied linearly as a function of the ratio of noise bandwidth and VARF. Periodicity per se did not appear to be a requirement for HFOV to occur, a result consistent with predictions of Taylor dispersion theory. PMID- 3106309 TI - Effects of cyclooxygenase inhibition on pulmonary vascular responses to serotonin. AB - The vasopressor response to graded bolus doses (50-500 micrograms) of serotonin (5-hydroxytryptamine; 5-HT) was examined in the isolated canine lower left lung lobe (LLL) perfused at constant flow with autogenous blood before and after cyclooxygenase inhibition (COI). Lobar vascular resistance (LVR) was partitioned into pre- (Ra) and postcapillary (Rv) segments by venous occlusion with lobar blood volume changes monitored gravimetrically. Before COI, 5-HT produced transient, dose-dependent increases in pulmonary arterial pressure (Ppa) of 43.8 +/- 4.8-123.0 +/- 8.5% (n = 22) and simultaneous decreases in lobar blood volume (5.5 +/- 0.5-8.2 +/- 0.6 g/100 g LLL) with nearly proportionate increases in Ra and Rv at each 5-HT dose. After the initial challenge to 5-HT, LLL's were treated either with saline (n = 7) or one of three chemically distinct cyclooxygenase inhibitors. COI with 40 microM indomethacin (n = 6) or 45 microM meclofenamate (n = 6) increased resting LVR by 36.0 +/- 8.3% (P less than 0.01; n = 12) and decreased the Ra/Rv from 1.9 +/- 0.3 to 1.1 +/- 0.2 (P less than 0.01), whereas 1 mM aspirin (n = 3) caused a fourfold increase in resting LVR without affecting Ra/Rv. After indomethacin or meclofenamate treatment, the vasopressor response to graded doses of 5-HT was markedly potentiated as Ppa increased by 71.6 +/- 7.6 207.0 +/- 24.6%. COI did not potentiate the lobar vasopressor response to graded doses (10-100 micrograms) of norepinephrine (NE, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106311 TI - Physiological neutrophil sequestration in the lung: visual evidence for localization in capillaries. AB - Although the lung is known to be a major site of neutrophil margination, the anatomic location of these sequestered cells within the lung is controversial. To determine the site of margination and the kinetics of neutrophil transit through the pulmonary microvasculature, we infused fluorescein isothiocyanate-labeled canine neutrophils into the pulmonary arteries of 10 anesthetized normal dogs and made fluorescence videomicroscopic observations of the subpleural pulmonary microcirculation through a window inserted into the chest wall. The site of fluorescent neutrophil sequestration was exclusively in the pulmonary capillaries with a total of 951 labeled cells impeded in the capillary bed for a minimum of 2 s. No cells were delayed in the arterioles or venules. Transit times of individual neutrophils varied over a wide range from less than 2 s to greater than 20 min with an exponential distribution skewed toward rapid transit times. These observations indicate that neutrophil margination occurs in the pulmonary capillaries with neutrophils impeded for variable periods of time on each pass through the lung. The resulting wide distribution of transit times may determine the dynamic equilibrium between circulating and marginated neutrophils. PMID- 3106312 TI - Ventilation-perfusion inequality during constant-flow ventilation. AB - Previous work by Lehnert et al. (J. Appl. Physiol. 53:483-489, 1982) has demonstrated that adequate alveolar ventilation can be maintained during apnea in anesthetized dogs by delivering a continuous stream of inspired ventilation through cannulas aimed down the main-stem bronchi. Because an asymmetric distribution of ventilation might introduce ventilation-perfusion (VA/Q) inequality, we compared gas exchange efficiency in nine anesthetized and paralyzed dogs during constant-flow ventilation (CFV) and conventional ventilation (intermittent positive-pressure ventilation, IPPV). Gas exchange was assessed using the multiple inert gas elimination technique. During CFV at 3 l X kg-1 X min-1, lung volume, retention-excretion differences (R-E*) for low- and medium-solubility gases, and the log standard deviation of blood flow (log SD Q) increased, compared with the findings during IPPV. Reducing CFV flow rate to 1 l X kg-1 X min-1 at constant lung volume improved R-E* and log SD Q, but significant VA/Q inequality compared with that at IPPV remained and arterial PCO2 rose. Comparison of IPPV and CFV at the same mean lung volume showed a similar reversible deterioration in gas exchange efficiency during CFV. We conclude that CFV causes significant VA/Q inequality which may be due to nonuniform ventilation distribution and a redistribution of pulmonary blood flow. PMID- 3106313 TI - Distribution of blood flow in muscles of miniature swine during exercise. AB - The purpose of this study was to determine how the distribution of blood flow within and among the skeletal muscles of miniature swine (22 +/- 1 kg body wt) varies as a function of treadmill speed. Radiolabeled microspheres were used to measure cardiac output (Q) and tissue blood flows in preexercise and at 3-5 min of treadmill exercise at 4.8, 8.0, 11.3, 14.5, and 17.7 km/h. All pigs (n = 8) attained maximal O2 consumption (VO2max) (60 +/- 4 ml X min-1 X kg-1) by the time they ran at 17.7 km/h. At VO2max, 87% of Q (9.9 +/- 0.5 l/min) was to skeletal muscle, which constituted 36 +/- 1% of body mass. Average total muscle blood flow at VO2max was 127 +/- 14 ml X min-1 X 100 g-1; average limb muscle flow was 135 +/- 17 ml X min-1 X 100 g-1. Within the limb muscles, blood flow was distributed so that the deep red parts of extensor muscles had flows about two times higher than the more superficial white portions of the same muscles; the highest muscle blood flows occurred in the elbow flexors (brachialis: 290 +/- 44 ml X min-1 X 100 g-1). Peak exercise blood flows in the limb muscles were proportional (P less than 0.05) to the succinate dehydrogenase activities (r = 0.84), capillary densities (r = 0.78), and populations of oxidative (slow-twitch oxidative + fast twitch oxidative-glycolytic) fiber types (r = 0.93) in the muscles. Total muscle blood flow plotted as a function of exercise intensity did not peak until the pigs attained VO2max, although flows in some individual muscles showed a plateau in this relationship at submaximal exercise intensities. The data demonstrate that blood flow in skeletal muscles of miniature swine is distributed heterogeneously and varies in relation to fiber type composition and exercise intensity. PMID- 3106314 TI - Ventilatory compensation for changes in functional residual capacity during sleep. AB - The role of conscious factors in the ventilatory compensation for shortened inspiratory muscle length and the potency of this compensatory response were studied in five normal subjects during non-rapid-eye-movement sleep. To shorten inspiratory muscles, functional residual capacity (FRC) was increased and maintained for 2-3 min at a constant level (range of increase 160-1,880 ml) by creating negative pressure within a tank respirator in which the subjects slept. Minute ventilation was maintained in all subjects over the entire range of increased FRC (mean change +/- SE = -3 +/- 1%) through preservation of tidal volume (-2 +/- 2%) despite slightly decreased breathing frequency (-6 +/- 2%). The decrease in frequency (-13 +/- 2%) was due to a prolongation in expiratory time. Inspiratory time shortened (-10 +/- 1%). Mean inspiratory flow increased 15 +/- 3% coincident with an increase in the slope of the moving time average of the integrated surface diaphragmatic electromyogram (67 +/- 21%). End-tidal CO2 did not rise. In two subjects, control tidal volume was increased 35-50% with CO2 breathing. This augmented tidal volume was still preserved when FRC was increased. We concluded that the compensatory response to inspiratory muscle shortening did not require factors associated with the conscious state. In addition, the potency of this response was demonstrated by preservation of tidal volume despite extreme shortening of the inspiratory muscles and increase in control tidal volumes caused by CO2 breathing. Finally, the timing changes we observed may be due to reflexes following shortening of inspiratory muscle length, increase in abdominal muscle length, or cardiovascular changes. PMID- 3106315 TI - Derivation of CO2 output from oscillations in arterial pH. AB - Theory predicts that the rate of rise of the oscillation in arterial CO2 partial pressure (PaCO2) is linearly dependent on CO2 flux from venous blood to alveolar gas. We have measured, in the anesthetized cat, CO2 output (VCO2) and oscillations in arterial pH. The pH signal was differentiated to give the maximum rate of fall of pH on the downstroke of the oscillation (dpH/dt decreases max). Since oscillations in pH are due to oscillations in arterial PCO2, dpH/dt decreases max was considered to be equivalent to the maximum rate of rise of the PCO2 oscillation. VCO2 was increased by ventilating the intestines with CO2 and by the intra-arterial infusion of 2,4-dinitrophenol. VCO2 was decreased by filling the intestines with isotonic tris(hydroxymethyl)methylamine buffer. The maximum range of VCO2 covered was 7.8-51 ml/min, and the mean range was from 13.6 +/- 1.3 to 29.7 +/- 1.6 (SE) ml/min. Although CO2 loading produced a small rise and CO2 unloading a small fall in mean PaCO2, the changes were not statistically significant, so that overall the response was close to isocapnia. Over the limited range of VCO2 studied there was a highly significant linear association between dpH/dt decreases max and VCO2 which supports the contention that the slope of the upstroke of the PaCO2 oscillation is determined by the CO2 flux from mixed venous blood to alveolar gas. As such this slope is a potential chemical signal linking ventilation to CO2 production. PMID- 3106316 TI - Initiation of pulmonary gas exchange by fetal sheep in utero. AB - The role of umbilical cord occlusion in the initiation of breathing at birth was investigated using unanesthetized fetal sheep that were provided with access to a tracheal supply of hyperoxic air. Near-term fetuses were studied in utero to eliminate extraneous sensory stimuli. Gasping movements began 1.4 +/- 0.1 min after cord occlusion. Breathing was irregular for several minutes before continuous breathing (greater than or equal to 40 min-1) began 6 +/- 1 min after cord occlusion (n = 10). Arterial PO2 rose significantly from 18 +/- 2 mmHg before occlusion and was 115 +/- 15 mmHg immediately before cord release at 15 or 30 min. Breathing continued even during high-voltage electrocortical activity. Cord release caused the breathing rate to decrease from 77 +/- 13 min-1 during the last 5 min of cord occlusion to 5 +/- 3 min-1 10 min after cord release (P less than 0.002; n = 7). Results indicate the change from placental to lung gas exchange can occur in the absence of sensory and thermal changes normally present at birth and that the transition is reversible. PMID- 3106317 TI - Diamine oxidase is important in assessment of polyamine effects on hemopoietic cell proliferation in vitro. AB - A difference was observed in the effect of difluoromethlyornithine (DFMO), a specific inhibitor of ornithine decarboxylase, on human and murine granulocyte macrophage precursor cell (CFU-C) proliferation in vitro, in the presence of fetal bovine serum (FBS) and horse serum (HS). A dose of DFMO which almost totally abolished CFU-C colonies in cultures containing FBS had no effect or very little effect on CFU-C in cultures supplemented with HS. This effect could be reversed by aminoguanidine reacting with diamine oxidase (DAO), which is present in FBS but not in HS. The importance of DAO in the assessment of polyamine effects is also suggested by decreased colony formation in cultures containing HS and DFMO only after the addition of this enzyme. Additionally, Mo T cell line cultures containing DFMO demonstrated a substantially lower intracellular concentration of putrescine in the presence of FBS rather than HS. PMID- 3106318 TI - Phylogenetic analysis of the coryneform bacteria by 5S rRNA sequences. AB - Nucleotide sequences of 5S rRNAs from 11 coryneform bacteria were determined. These were the type strains of Corynebacterium glutamicum, Corynebacterium xerosis, Brevibacterium linens, Arthrobacter globiformis, Cellulomonas biazotea, Aureobacterium testaceum, Curtobacterium citreum, Pimelobacter simplex, and Caseobacter polymorphus and representative strains of "Corynebacterium aquaticum" and Corynebacterium xerosis. A phylogenetic tree constructed from the sequences of these bacteria and published sequences indicated that the coryneform bacteria consist of a distinct eubacterial branch together with Streptomyces and Micrococcus spp. These bacteria could be further divided into four subgroups. PMID- 3106319 TI - Genetic analysis of RNA polymerase-promoter interaction during sporulation in bacillus subtilis. AB - The discovery of secondary sigma factors in Bacillus subtilis that enable RNA polymerase to transcribe cloned sporulation genes in vitro has led to the proposal that the appearance of new sigma factors during sporulation directs RNA polymerase to the different temporal classes of sporulation genes. One sigma factor, which appears 2 h after the initiation of sporulation, is sigma E (formerly sigma 29). Mutations that inactivate the structural gene for sigma E prevent transcription from promoter G4. To determine whether sigma E-RNA polymerase interacts with the G4 promoter in vivo, we examined the effects of six single-base-pair substitutions in the G4 promoter on its utilization in vivo and in vitro by sigma E-RNA polymerase. The mutations in the G4 promoter affected utilization of the promoter in vivo in the same way that they affected its utilization in vitro by purified sigma E-RNA polymerase; therefore, we conclude that this polymerase interacts directly with the G4 promoter in vivo. The effects of these mutations also support the model in which sigma E-RNA polymerase utilizes promoters by interacting with two distinct sets of nucleotides located 10 and 35 base pairs upstream from the start point of transcription. PMID- 3106320 TI - Functional expression of plastid allophycocyanin genes in a cyanobacterium. AB - In Cyanophora paradoxa, the allophycocyanin apoprotein subunits, alpha and beta, are encoded in the cyanelle (plastid) genome. These genes were transferred to the cyanobacterium Synechococcus sp. PCC 7002 on a plasmid replicon. Phycobilisomes isolated from transformed cyanobacteria were found to contain C. paradoxa allophycocyanin subunits. Thus, these plastid genes are expressed in the cyanobacterium as polypeptides which become linked to a chromophore and are incorporated into the light-harvesting apparatus. PMID- 3106321 TI - Cloning and characterization of the c1 repressor of Pseudomonas aeruginosa bacteriophage D3: a functional analog of phage lambda cI protein. AB - We cloned the gene (c1) which encodes the repressor of vegetative function of Pseudomonas aeruginosa bacteriophage D3. The cloned gene was shown to inhibit plating of D3 and the induction of D3 lysogens by UV irradiation. The efficiency of plating and prophage induction of the heteroimmune P. aeruginosa phage F116L were not affected by the presence of the cloned c1 gene of D3. When the D3 DNA fragment containing c1 was subcloned into pBR322 and introduced into Escherichia coli, it was shown to specifically inhibit the plating of phage lambda and the induction of the lambda prophage by mitomycin C. The plating of lambda imm434 phage was not affected. Analysis in minicells indicated that these effects correspond to the presence of a plasmid-encoded protein of 36,000 molecular weight. These data suggest the possibility that coliphage lambda and the P. aeruginosa phage D3 evolved from a common ancestor. The conservation of the functional similarities of their repressors may have occurred because of the advantage to these temperate phages of capitalizing on the potential of the evolutionarily conserved RecA protein to monitor the level of damage to the host genome. PMID- 3106322 TI - Molybdenum-sensitive transcriptional regulation of the chlD locus of Escherichia coli. AB - The chlD gene in Escherichia coli is required for the incorporation and utilization of molybdenum when the cells are grown with low concentrations of molybdate. We constructed chlD-lac operon fusions and measured expression of the fusion, Mo cofactor, and nitrate reductase activities under a variety of growth conditions. The chlD-lac fusion was highly expressed when cells were grown with less than 10 nm molybdate. Increasing concentrations of molybdate caused loss of activity, with less than 5% of the activity remaining at 500 nM molybdate; when tungstate replaced molybdate, it had an identical affect on chlD expression. Expression of chlD-lac was increased in cells grown with nitrate. Strains with chlD-lac plus an additional mutation in a chl or nar gene were constructed to test whether the regulation of chlD-lac required the concerted action of gene products involved with Mo cofactor or nitrate reductase synthesis. Mutations in narL prevented the increase in activity in response to nitrate; mutations in chlB, narC, or narI resulted in partial constitutive expression of the chlD-lac fusion: the fusion was regulated by molybdate, but it no longer required the presence of nitrate for maximal activity. Mutations in chlA, chlE, or chlG which affect Mo cofactor metabolism, did not affect the expression of chlD-lac. PMID- 3106323 TI - The Escherichia coli dnaJ mutation affects biosynthesis of specific proteins, including those of the lac operon. AB - Temperature-sensitive dnaJ mutants of Escherichia coli showed a thermosensitive defect in the synthesis of beta-galactosidase. Synthesis of the lac mRNA was greatly reduced at the restrictive temperature. The mutants were also conditionally defective in the synthesis of a subset of membrane proteins such as succinate dehydrogenase, whereas the synthesis of anthranilate synthetase, encoded by trpED, as well as that of most cellular proteins, was unaffected at the restrictive temperature. The defect was specific for the dnaJ mutants among several dna mutants which are known to be involved in the initiation of DNA synthesis: dnaK, dnaA, and dnaB mutants synthesized each of these proteins normally even at the restrictive temperature. At the restrictive temperature, growth of the dnaJ mutants was arrested at a specific stage of the cell cycle. PMID- 3106324 TI - Nucleotide sequence of the streptothricin acetyltransferase gene from Streptomyces lavendulae and its expression in heterologous hosts. AB - The nucleotide sequence of the streptothricin acetyltransferase (STAT) gene from streptothricin-producing Streptomyces lavendulae predicts a 189-amino-acid protein of molecular weight 20,000, which is consistent with that determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme. The amino acid composition and the NH2-terminal sequence determined by using the purified protein are in good agreement with those predicted from the nucleotide sequence, except for the absence of the NH2-terminal methionine in the mature protein. High-resolution S1 nuclease protection mapping suggests that transcription initiates at or near the adenine residue which is the first position of the translational initiation triplet (AUG) of STAT. Another open reading frame located just upstream of the STAT gene was detected and contains a region bearing a strong resemblance to DNA-binding domains which are conserved in known DNA-binding proteins. By addition of promoter signals and a synthetic ribosome-binding (Shine-Dalgarno) sequence at an appropriate position upstream of the STAT translational start codon, the STAT gene confers streptothricin resistance on Escherichia coli and Bacillus subtilis. The STAT coding sequence with both the promoter of a B. subtilis cellulase gene and a synthetic Shine Dalgarno sequence was functionally expressed in Streptomyces lividans, which suggests that the addition of an artificial leader upstream of the translational initiation codon (AUG) does not significantly influence the translation of STAT. PMID- 3106325 TI - Effect of growth temperature on the lipids, outer membrane proteins, and lipopolysaccharides of Pseudomonas aeruginosa PAO. AB - Growth of Pseudomonas aeruginosa PAO1 at 15 to 45 degrees C in tryptic soy broth resulted in changes in the lipids, lipopolysaccharides (LPSs), and outer membrane proteins of the cells. Cells grown at 15 degrees C contained, relative to those cultivated at 45 degrees C, increased levels of the phospholipid fatty acids hexadecenoate and octadecenoate and reduced levels of the corresponding saturated fatty acids. Furthermore, the lipid A fatty acids also showed thermoadaptation with decreases in dodecanoic and hexadecanoic acids and increases in the level of 3-hydroxydecanoate and 2-hydroxdodecanoate as the growth temperature decreased. In addition, LPS extracted from cells cultivated at the lower temperatures contained a higher content of long-chain S-form molecules than that isolated from cells grown at higher temperatures. On the other hand, the percentage of LPS cores substituted with side-chain material decreased from 37.6 mol% at 45 degrees C to 19.3 mol% at 15 degrees C. The outer membrane protein profiles indicated that at low growth temperatures there was an increase in a polypeptide with an apparent molecular weight of 43,000 and decreases in the content of 21,000 (protein H1)- and 27,500-molecular-weight proteins. PMID- 3106326 TI - Cloning, nucleotide sequencing, and genetic mapping of the gene for small, acid soluble spore protein gamma of Bacillus subtilis. AB - The Bacillus subtilis gene (sspE) which codes for small acid-soluble spore protein gamma (SASP-gamma) was cloned, and its chromosomal location (65 degrees, linked to glpD) and nucleotide sequence were determined. The amino acid sequence of SASP-gamma is similar to that of SASP-B of Bacillus megaterium, but these sequences are not as highly conserved across species as are those of other SASPs. The SASP-gamma gene is transcribed only in sporulation in parallel with other SASP genes and gives a single mRNA that is approximately 340 nucleotides long. The results of hybridization of an sspE gene probe to Southern blots of B. subtilis DNA suggested that there is only a single gene coding for the SASP-gamma type of protein in B. subtilis. This was confirmed by introducing a deletion mutation into the cloned sspE gene and transferring the deletion into the B. subtilis chromosome, with concomitant loss of the wild-type gene. This sspE deletion strain sporulated well, but lacked the SASP-gamma type of protein. PMID- 3106327 TI - Genetic and physical mapping and expression in Pseudomonas aeruginosa of the chromosomally encoded ribulose bisphosphate carboxylase genes of Alcaligenes eutrophus. AB - We have previously shown that functional ribulose bisphosphate carboxylase (RuBPCase, rbc) genes in Alcaligenes eutrophus ATCC 17707 are present both on the chromosome and on the indigenous plasmid pAE7. Here we demonstrate that the chromosomal rbc locus encodes both a large (rbcL)- and a small (rbcS)-subunit gene. A 2.3-kilobase DNA fragment containing both subunit genes was subcloned into the broad-host-range vector pRK310 to yield plasmid pAE312. This plasmid was transferred into Pseudomonas aeruginosa in which expression of both the rbcL and rbcS genes took place, as demonstrated by Western blot analysis. A high level of RuBPCase activity was observed for P. aeruginosa(pAE312), suggesting that assembly of the subunits took place. Plasmid pAE312 was mutagenized with Tn5 in Escherichia coli. Complementation of A. eutrophus RuBPCase structural gene mutants with pAE312 containing mapped Tn5 insertions allowed functional analysis of the rbc gene region. The polar effect of the Tn5 insertions suggested that the two subunit genes were cotranscribed in A. eutrophus, with rbcL located promoter proximal. Northern blot analysis of total RNA from P. aeruginosa(pAE312) confirmed cotranscription of the two subunit genes. DNA probes containing both the rbcL and rbcS genes, or fragments of each gene, all hybridized to a predominant transcript about 2.1-kilobases long. These observations indicate that the chromosomally encoded rbcL and rbcS genes of A. eutrophus constitute an operon. PMID- 3106328 TI - Endo-beta-1,4-glucanase gene of Bacillus subtilis DLG. AB - The DNA sequence of the Bacillus subtilis DLG endo-beta-1,4-glucanase gene was determined, and the in vivo site of transcription initiation was located. Immediately upstream from the transcription start site were sequences closely resembling those recognized by B. subtilis sigma 43-RNA polymerase. Two possible ribosome-binding sites were observed downstream from the transcription start site. These were followed by a long open reading frame capable of encoding a protein of ca. 55,000 daltons. A signal sequence, typical of those present in gram-positive organisms, was observed at the amino terminus of the open reading frame. Purification of the mature exocellular beta-1,4-glucanase and subsequent amino-terminal protein sequencing defined the site of signal sequence processing to be between two alanine residues following the hydrophobic portion of the signal sequence. The probability of additional carboxy-terminal processing of the beta-1,4-glucanase precursor is discussed. S1 nuclease protection studies showed that the amount of beta-1,4-glucanase mRNA in cells increased significantly as the culture entered the stationary phase. In addition, glucose was found to dramatically stimulate the amount of beta-1,4-glucanase mRNA in vivo. Finally, the specific activities of purified B. subtilis DLG endo-beta-1,4-glucanase and Trichoderma reesei QM9414 endo-beta-1,4-glucanase (EC 3.2.1.4) were compared by using the noncrystalline cellulosic substrate trinitrophenyl-carboxymethyl cellulose. PMID- 3106329 TI - Anaerobic catabolism of formate to acetate and CO2 by Butyribacterium methylotrophicum. AB - The catabolism of sodium formate to acetate and carbon dioxide by the anaerobic acetogen Butyribacterium methylotrophicum was analyzed by fermentation time course and 13C nuclear magnetic resonance studies. Significant hydrogen production and consumption fluxes were observed during formate catabolism but not during the catabolism of formate plus CO. In the latter case, formate and CO were simultaneously consumed and label distribution studies with mixtures of 13C labeled CO and formate demonstrated their preferential incorporation into the acetate carboxyl and methyl groups, respectively. Hydrogen consumption was inhibited by CO when both were present, whereas hydrogen and formate were simultaneously consumed when CO2 was supplied. Carbon dioxide was required for the conversion of CO to acetate, but a similar need was not observed when methanol plus CO or formate plus CO was present. These analyses indicate a bifurcated single-carbon catabolic pathway in which CO2 is the sole single-carbon compound that directly supplies the carbonyl and methyl group synthesis pathways leading to the formation of acetyl coenzyme A, the primary reduced product. We discuss causes for the reported inability of B. methylotrophicum to use formate as a sole substrate. PMID- 3106330 TI - Gene fusion is a possible mechanism underlying the evolution of STA1. AB - DNA from the STA1 (extracellular glucoamylase) gene of Saccharomyces diastaticus was used as a probe to enable the cloning by colony hybridization of three DNA fragments from Saccharomyces cerevisiae; these were designated S1, S2, and SGA (intracellular, sporulation-specific glucoamylase gene). To examine the evolutionary relationship among these sequences at the nucleotide level, we sequenced S2, S1, SGA and compared them with STA1. These data and RNA blot analysis revealed that the following regions of STA1 were highly conserved in S2, S1, and SGA: upstream regulatory sequences responsible for transcription, a signal sequence for protein secretion, a threonine- and serine-rich domain, and a catalytic domain for glucoamylase activity. These results suggest that an ancestral STA gene was generated relatively recently in an evolutionary time scale by the sequential fusions of S2, S1, and SGA, with S1 functioning as a connector for S2 and SGA. We describe a model for the involvement of short nucleotide sequences flanking the junctions in the gene fusions. PMID- 3106331 TI - Regulation of the aroH operon of Escherichia coli by the tryptophan repressor. AB - Regulation of expression of aroH, the structural gene for the tryptophan sensitive 3-deoxy-D-arabinoheptulosonic acid-7-phosphate synthetase, by the tryptophan repressor and its corepressor, L-tryptophan, was studied in vivo by using aroH-lacZ fusions. Protein and operon fusions were constructed on multicopy plasmids and subsequently crossed in single copy to the bacterial chromosome via the specialized transducing bacteriophage lambda RZ5. Analysis of the resulting lysogens demonstrated that aroH-lacZ expression in a trpR mutant strain varied four- to fivefold relative to an isogenic trpR+ strain under fully repressing conditions. In trpR+ strains containing either fusion, a modest (ca. 50%) change in activity was seen in response to the addition of L-tryptophan to the culture medium. These data demonstrate that aroH gene expression is only moderately regulated by the tryptophan repressor and that this regulation is at the level of transcription. Addition of L-phenylalanine, L-tyrosine, or Casamino Acids (Difco Laboratories, Detroit, Mich.) to the cell culture medium resulted in a tryptophan repressor-dependent derepression of aroH expression. We believe that this effect is caused by L-tryptophan limitation as a result of repression and feedback inhibition of the tyrosine- and phenylalanine-specific 3-deoxy-D arabinoheptulosonic acid-7-phosphate synthetase isoenzymes. Derepression of aroH expression by the L-tryptophan analogs, 3-beta-indoleacrylic acid and indole-3 propionic acid, is also documented. PMID- 3106332 TI - Use of bacterial luciferase to establish a promoter probe vehicle capable of nondestructive real-time analysis of gene expression in Bacillus spp. AB - We report the construction and use of a new promoter probe vehicle capable of allowing extremely sensitive measurements of transcriptional activity promoted from random, chromosomal DNA fragment inserts. Coupled with the advantage of sensitivity, the detection system is noninvasive, nondestructive, and provides real-time reportage of expression potential. These latter aspects make it an especially valuable system for a continuing analysis of the complex transcriptional regulation patterns now recognized as a dominant control feature during the differentiation and morphogenesis characteristic of the sporulation cycle in Bacillus species. In this respect we describe the isolation of DNA fragments from B. megaterium and B. subtilis capable of initiating transcription in both the respective parent organisms and, in certain instances, also in Escherichia coli. Detailed luminescence studies showed that several promoter regions which are entirely or substantially developmentally controlled were isolated. PMID- 3106333 TI - Structure of the Bacillus subtilis pyrimidine biosynthetic (pyr) gene cluster. AB - A 10.5-kilobase PstI endonuclease fragment encoding the entire Bacillus subtilis pyrimidine biosynthetic (pyr) gene cluster was cloned in Escherichia coli by transformation of a carB strain to uracil-independent growth. The cloned fragment also complemented E. coli pyrB, pyrC, pyrD, pyrE, and pyrF mutants. From the ability of subclones to complement E. coli pyr mutants, the gene order was deduced to be pyrBCADFE. The B. subtilis pyrB gene was shown to be expressed in E. coli, but synthesis of the enzyme was not repressible by the addition of uracil to the growth medium. The approximate molecular weights of the polypeptides encoded by B. subtilis pyrA, pyrB, pyrC, pyrD, pyrE, and pyrF were found to be 110,000, 36,000, 46,000, 34,000, 25,000, and 27,000, respectively. PMID- 3106334 TI - Regulation of the glutamate-glutamine transport system by intracellular pH in Streptococcus lactis. AB - Various methods of manipulation of the intracellular pH in Streptococcus lactis result in a unique relationship between the rate of glutamate and glutamine transport and the cytoplasmic pH. The initial rate of glutamate uptake by S. lactis cells increases more than 30-fold when the intracellular pH is raised from 6.0 to 7.4. A further increase of the cytoplasmic pH to 8.0 was without effect on transport. The different levels of inhibition of glutamate and glutamine transport at various external pH values by uncouplers and ionophores, which dissipate the proton motive force, can be explained by the effects exerted on the intracellular pH. The dependence of glutamate transport on the accumulation of potassium ions in potassium-filled and -depleted cells is caused by the regulation of intracellular pH by potassium movement. PMID- 3106335 TI - Phosphoenolpyruvate:sugar phosphotransferase system of Bacillus subtilis: cloning of the region containing the ptsH and ptsI genes and evidence for a crr-like gene. AB - The genes ptsI and ptsH, which encode, respectively, enzyme I and Hpr, cytoplasmic proteins involved in the phosphoenolpyruvate:sugar phosphotransferase system, were cloned from Bacillus subtilis. A plasmid containing a 4.1-kilobase DNA fragment was shown to complement Escherichia coli mutations affecting the ptsH and ptsI genes. In minicells this plasmid expressed two proteins with the molecular weights expected for Hpr and enzyme I. Therefore, ptsH and ptsI are adjacent in B. subtilis, as in E. coli. In E. coli a third gene (crr), involved in glucose translocation and also in catabolite repression, is located downstream from the ptsHI operon. The 4.1-kilobase fragment from B. subtilis was shown to contain a gene that enables an E. coli crr mutant to use glucose. This gene, unlike the E. coli crr gene, was located to the left of ptsH. PMID- 3106336 TI - Purification and properties of the hydroxylase component of methane monooxygenase. AB - Methane monooxygenase from Methylobacterium sp. strain CRL-26 which catalyzes the oxygenation of hydrocarbons was resolved into two components, a hydroxylase and a flavoprotein. An anaerobic procedure was developed for the purification of the hydroxylase to homogeneity. The molecular weight of the hydroxylase as determined by gel filtration was 220,000, and that determined by sedimentation equilibrium analysis was about 225,000. The purified hydroxylase contained three nonidentical subunits with molecular weights of about 55,000, 40,000, and 20,000, in equal amounts as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that it is an alpha 2 beta 2 gamma 2 protein. Optical absorption spectra revealed peaks near 408 and 280 nm, and fluorescence spectra revealed emission peaks at 490 and 630 nm. The purified hydroxylase contained 2.8 +/- 0.2 mol of iron and 0.5 +/- 0.1 mol of zinc per mol of protein but negligible amounts of acid-labile sulfide. The antisera prepared against the hydroxylase showed cross-reactivity with hydroxylase components in soluble extracts from other methanotrophs. PMID- 3106337 TI - Identification and characterization of UDP-GalNAc: NeuAc alpha 2-3Gal beta 1 4Glc(NAc) beta 1-4(GalNAc to Gal)N-acetylgalactosaminyltransferase in human blood plasma. AB - Normal human plasma was found to contain beta 1-4N acetylgalactosaminyltransferase catalyzing the transfer of N-acetylgalactosamine from UDP-GalNAc to 3'-sialyl-lactose, NeuAc alpha 2-3Gal beta 1-4Glc. The transferred N-acetylgalactosaminyl residue was cleaved from the desialylated reaction product by the beta-N-acetylhexosaminidase from jack beans. Methylation and hydrolysis of the desialylated reaction product yielded only 2,3,6-tri-O methylgalactose and 2,3,6-tri-O-methylglucose as neutral sugars, indicating that the N-acetylgalactosaminyl residue was introduced at position C-4 of the galactosyl residue of 3'-sialyllactose. The enzyme required Mn2+ ions for its activity and showed a pH optimum between 6.5 and 8.5. By using a wide variety of oligosaccharides and glycoconjugates, the acceptor specificity of the beta 1-4N acetylgalactosaminyltransferase was investigated. No detectable amount of N acetylgalactosamine was transferred to either 6'-sialyllactose or lactose. The enzyme did not act on ganglioside GM3, NeuAc alpha 2-3Gal beta 1-4Glc-ceramide, suggesting that the hydrophobic ceramide portion of GM3 interferes with the enzyme reaction. On the other hand, glycoproteins carrying terminal NeuAc alpha 2 3Gal beta 1-4GlcNAc structures on their N-linked oligosaccharide chains, e.g. Tamm-Horsfall glycoprotein, were efficient acceptors. PMID- 3106338 TI - Incorporation of coenzyme M into component C of methylcoenzyme M methylreductase during in vitro methanogenesis. AB - Reduction of the methyl group of [methyl-3H,thio-35S]2-methylthioethanesulfonic acid to methane by a reconstituted enzyme system resulted in a slow incorporation of [thio-35S]2-mercaptoethanesulfonic acid (HS-CoM) into component C of the methylreductase system. Only 35S label was associated with component C. The ratio of incorporated HS-CoM to component C was 1.96 to 1. The ratio of HS-CoM to factor F430, the nickel-containing cofactor of component C, was 1.18 to 1. Extraction of factor F430 from the protein resulted in the release of 62 +/- 8% of the 35S label, but the label was not covalently bound to F430. The incorporation of label into component C was coupled to methyl group reduction; no label was found associated with component C from a reconstituted reaction containing unlabeled 2-methylthioethanesulfonic acid and [thio-35S]HS-CoM. PMID- 3106339 TI - Genistein, a specific inhibitor of tyrosine-specific protein kinases. AB - Tyrosine-specific protein kinase activity of the epidermal growth factor (EGF) receptor, pp60v-src and pp110gag-fes was inhibited in vitro by an isoflavone genistein. The inhibition was competitive with respect to ATP and noncompetitive to a phosphate acceptor, histone H2B. By contrast, genistein scarcely inhibited the enzyme activities of serine- and threonine-specific protein kinases such as cAMP-dependent protein kinase, phosphorylase kinase, and the Ca2+/phospholipid dependent enzyme protein kinase C. When the effect of genistein on the phosphorylation of the EGF receptor was examined in cultured A431 cells, EGF stimulated serine, threonine, and tyrosine phosphorylation was decreased. Phosphoamino acid analysis of total cell proteins revealed that genistein inhibited the EGF-stimulated increase in phosphotyrosine level in A431 cells. PMID- 3106340 TI - Regulation of acetyl-CoA:1-alkyl-sn-glycero-3-phosphocholine O2-acetyltransferase (lyso-PAF-acetyltransferase) in exocrine glands. Evidence for an activation via phosphorylation by calcium/calmodulin-dependent protein kinase. AB - Stimulation of secretion in guinea pig exocrine cells is associated with an enhanced synthesis in these cells of 1-O-alkyl-2-sn-acetyl-glycero-3 phosphocholines (PAF) from 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (Soling, H-D., and Fest, W. (1986) J. Biol. Chem. 261, 13916-13922). This results from a stimulation of the activity of lyso-1-alkylglycerophosphocholine acetyltransferase (EC 2.3.1.67). Here we have analyzed the effects of various agonists on the activity of this enzyme in guinea pig parotid gland microsomes. Carbamoylcholine leads within less than 30 s to a 2- to 4-fold activation of lyso PAF-acetyltransferase, which persists after solubilization of the microsomal enzyme with octyl glucoside. The calcium ionophore A23187 has a similar though smaller effect. Neither isoproterenol (2 X 10(-5) M), which stimulates exocytosis more than carbachol, nor phorbol ester significantly affected lyso-PAF acetyltransferase activity. Incubation of microsomes from unstimulated parotid gland acini with cAMP-dependent and calcium/calmodulin-dependent protein kinase resulted in a 4-fold and 2.9-fold activation of lyso-PAF-acetyltransferase activity, respectively. Protein kinase C had no significant effect. Activation with calcium/calmodulin-dependent protein kinase was inhibited by 40 microM trifluoperazine. When microsomes from carbachol-stimulated glands were used, in vitro activation of the enzyme by calcium/calmodulin-dependent protein kinase was almost abolished. Protein phosphatase 2A in vitro strongly reduced lyso-PAF acetyltransferase activity in microsomes from both stimulated and unstimulated glands, whereas alkaline phosphatase and protein phosphatase 1 had only small effects. Following treatment with protein phosphatase 2A, enzyme activity in microsomes from stimulated glands could be enhanced more than 8-fold by subsequent incubation with calcium/calmodulin-dependent protein kinase. Although unsuccessful attempts have made it impossible so far to demonstrate directly the incorporation of phosphate into lyso-PAF-acetyltransferase, the results reported here strongly suggest that the enzyme in exocrine cells is regulated by phosphorylation-dephosphorylation and that a calcium/calmodulin-dependent protein kinase is responsible for the activation of the enzyme and type-2 protein phosphatases for its inactivation. PMID- 3106341 TI - Characterization of recombinant human single chain urokinase-type plasminogen activator mutants produced by site-specific mutagenesis of lysine 158. AB - The cDNA encoding full-length single chain urokinase-type plasminogen activator (scu-PA) was cloned and sequenced, and the recombinant scu-PA (rscu-PA) was expressed in Chinese hamster ovary cells. Two mutants, constructed by in vitro site-specific mutagenesis of Lys158 in rscu-PA to Gly158 (rscu-PA-Gly158) or to Glu158 (rscu-PA-Glu158), were also expressed in Chinese hamster ovary cells. Wild type and mutant rscu-PAs were purified to homogeneity by immunoadsorption on an insolubilized monoclonal antibody raised against natural scu-PA (nscu-PA), followed by gel filtration. The specific activity of the mutant scu-PAs on fibrin plates is very low (less than 1,000 IU/mg) compared to that of the wild type rscu PA (44,000 IU/mg). The mutants, in contrast to the wild type rscu-PA, are not converted to amidolytically active two chain u-PA (tcu-PA) by plasmin and do not cause lysis of a 125I-fibrin-labeled plasma clot immersed in citrated plasma. However, in a purified system, both rscu-PA-Gly158 and rscu-PA-Glu158 activate plasminogen following Michaelis-Menten kinetics, with a much lower affinity (Km = 60-80 microM) but with a higher turnover rate constant (k2 = 0.01 s-1) as compared to the wild type rscu-PA (Km = 1.0 microM, k2 = 0.002 s-1). We conclude that conversion of scu-PA to tcu-PA is not a prerequisite for the activation of plasminogen. Substitution of Lys158 by Gly158 or Glu158 does, however, markedly decrease the stability of the Michaelis complex. PMID- 3106342 TI - Structure-function analysis of human interleukin-2. Identification of amino acid residues required for biological activity. AB - To locate functional domains of the interleukin-2 (IL-2) protein, a cDNA clone encoding biologically active human IL-2 was mutagenized using synthetic oligonucleotides to incorporate defined amino acid substitutions and deletions in the mature protein. The IL-2 analogs were then produced in Escherichia coli and assayed for the ability to induce proliferation of IL-2-dependent cells and the ability to compete for binding to the IL-2 receptor. Our analysis of over 50 different mutations demonstrated that the integrity of at least three regions of the IL-2 molecule is required for full biological activity: the NH2 terminus (residues 1-20), the COOH terminus (residues 121-133), and 2 of the 3 cysteine residues (58 and 105). Deletion of the NH2-terminal 20 amino acids or the COOH terminal 10 amino acids resulted in the loss of greater than 99% of bioactivity and binding. Amino acid substitutions at specific positions in these regions also resulted in proteins which retained less than 1% activity. The NH2 terminus and an adjacent internal region were recognized by neutralizing anti-IL-2 antibodies. In combination with the results from epitope competition analysis with neutralizing antibodies, these data are consistent with the IL-2 protein being folded such that the NH2 terminus, the COOH terminus, and the internal 30- to 60 region are juxtaposed to form the binding site recognized by the IL-2 receptor. PMID- 3106343 TI - Platelet-activating factor stimulation of rabbit platelets is blocked by serine protease inhibitor (chymotryptic protease inhibitor). AB - The serine protease inhibitors diethyl p-nitrophenyl phosphate and phenylmethylsulfonyl fluoride (chemical modifiers of serine residue) and N-acetyl l-tryptophan ethyl ester (competitive inhibitor of chymotryptic protease) inhibited 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC; platelet activating factor)-induced platelet aggregation and secretion. The inhibition was dependent on the preincubation time with the serine protease inhibitor and on the concentration of AGEPC and inhibitor. The IC50 value of diethyl-p-nitrophenyl phosphate, phenylmethylsulfonyl fluoride, and N-acetyl-l-tryptophan ethyl ester towards 5 X 10(-10) M AGEPC in serotonin release was 2.2 X 10(-4), 8.0 X 10(-4), and 5.0 X 10(-4) M, respectively. In experiments where platelets were incubated with these inhibitors and then washed with buffer, the inhibition of AGEPC stimulation was not observed. Prostaglandin H2 analog U46619 (10(-6) to 10(-5) M) and thrombin (0.1 unit/ml)-induced platelet activation were also blocked by 1 mM diethyl p-nitrophenyl phosphate and 1 mM N-acetyl-l-tryptophan ethyl ester. The binding of AGEPC (1.5 X 10(-11) to 9.4 X 10(-10) M) to platelets and the platelet cyclic AMP level were not affected by diethyl p-nitrophenyl phosphate, phenylmethylsulfonyl fluoride, and N-acetyl-l-tryptophan ethyl ester. However, 1 mM diethyl p-nitrophenyl phosphate and 1 mM N-acetyl-l-tryptophan ethyl ester suppressed 10(-9) M AGEPC-induced breakdown of phosphatidylinositol 4,5 bisphosphate and formation of phosphatidic acid to 10-12 and 39-42%, 40-kDa protein phosphorylation to 4 and 30%, and arachidonic acid release to 17 and 28% of controls, respectively. On the other hand, 5 mM diethyl p-nitrophenyl phosphate did not inhibit diacylglycerol production and arachidonic acid release initiated by 2.5 mM deoxycholate treatment, suggesting that receptor-mediated phospholipase C and phospholipase A2 activation were inhibited by the serine protease inhibitor, but the deoxycholate (physicochemical stimulant)-initiated activation was not. AGEPC-induced 20-kDa protein phosphorylation and the inhibitory action of AGEPC on cyclic AMP accumulation were abolished in the presence of diethyl p-nitrophenyl phosphate and phenylmethylsulfonyl fluoride. However, a tryptic protease inhibitor, 1 mM p-aminobenzamidine and 1 mM benzoyl-l arginine methyl ester, did not prevent the AGEPC-induced platelet secretion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3106344 TI - Identification of the mucin core protein by cell-free translation of messenger RNA from bovine submaxillary glands. AB - Bovine submaxillary mucin was purified and subjected to chemical deglycosylation by treatment at 20 degrees C with either anhydrous hydrogen fluoride or trifluoromethane sulfonic acid. Virtually all of the sialic acid, galactose, fucose, and over 90% of the N-acetylhexosamines were removed by these treatments. The amino acid compositions of the deglycosylated and native mucins were similar indicating that chemical deglycosylation did not cause significant degradation of the protein. Antiserum specific for the deglycosylated bovine submaxillary mucin was produced by immunization of rabbits with the deglycosylated mucin. RNA was isolated from bovine submaxillary glands by extraction with guanidine hydrochloride and further fractionated by chromatography on oligo(dT)-cellulose to yield poly(A)+ mRNA. The poly(A)+ mRNA was translated in a rabbit reticulocyte cell-free translation system using [35S]methionine, [3H]leucine, [3H]threonine, [3H]proline, or [3H]serine as radiolabel and the translation products were analyzed by gel electrophoresis and fluorography before and after immunoprecipitation with the antiserum. A labeled product of molecular weight 60,000 was present in the immunoprecipitates obtained in the absence but not in the presence of the unlabeled competitor deglycosylated mucin. It is concluded that the primary translation product of the bovine submaxillary gland gene is a 60,000-dalton protein and that the monomer subunit of the mucin is about 170,000. Thus, in the native state the mucin consists of several self-associating subunits. PMID- 3106345 TI - Fibrinogen lysine residue A alpha 157 plays a crucial role in the fibrin-induced acceleration of plasminogen activation, catalyzed by tissue-type plasminogen activator. AB - In previous studies, we have shown that the stretch 148-197 of the fibrinogen A alpha chain plays a crucial role in the acceleration of the tissue-type plasminogen activator (t-PA)-catalyzed plasminogen activation. In this study we have synthesized parts of A alpha 148-197 and analogues thereof. We found that the peptides with sequences identical with A alpha 148-161 and A alpha 149-161 of human fibrinogen accelerate the plasminogen activation by t-PA, whereas the corresponding peptides in which lysine residues A alpha 157 had been replaced by valine or arginine had no accelerating capacity. Furthermore, succinylation of the lysine residue(s) in the synthesized peptides A alpha 148-161 and A alpha 149 161 leads to loss of accelerating action. These findings show that lysine residue A alpha 157 is crucial for the accelerating action of fibrin on the t-PA catalyzed plasminogen activation. PMID- 3106346 TI - Basement membrane procollagen IV and its specialized carboxyl domain are conserved in Drosophila, mouse, and human. AB - Interaction with the extracellular matrix is important for the proliferation and differentiation of cells during development. A specialized extracellular matrix, basement membrane, is built around a scaffold of procollagen IV molecules. We report the sequence of a 2.5-kilobase cDNA which contains the carboxyl end of a Drosophila melanogaster procollagen IV. The amino acid sequence of the carboxyl terminal domain, which forms an essential intermolecular linkage between procollagen IV molecules, is 59% identical in Drosophila and vertebrate procollagens IV, and an additional 17% of residues are conservatively substituted. This implies that the nature of the linkage is also conserved. We suggest that intermolecular junctions through procollagen IV carboxyl domains are fundamental elements of the molecular architecture of Metazoan basement membranes and have been conserved during evolution. The isolation and identification of this basement membrane collagen gene of Drosophila will help in deducing the function of procollagen IV in basement membranes. PMID- 3106347 TI - Interaction between the calcium and adenylate cyclase messenger systems in dispersed chief cells from guinea pig stomach. Possible cellular mechanism for potentiation of pepsinogen secretion. AB - To determine the role of the adenylate cyclase system in potentiation of enzyme secretion, we used cholera toxin to activate adenylate cyclase before examining the effects of agents on chief cell cAMP and pepsinogen secretion. Dispersed chief cells were obtained from guinea pig stomach by fractionation of mucosal cells on a Percoll gradient. Incubation of cells with 100 nM cholera toxin for 90 min and subsequent incubation with carbachol or cholecystokinin resulted in augmentation of cellular cAMP and potentiation of pepsinogen secretion. The rate of increase in cAMP with carbachol or cholecystokinin was similar to that for the potentiated secretory response. To determine the role of changes in cell calcium on these effects, we examined the actions of the ionophore A23187. In cells preincubated with cholera toxin, A23187 augmented cAMP and caused potentiation of pepsinogen secretion. The effects of A23187, carbachol, and cholecystokinin on cells preincubated with cholera toxin were abolished by removing extracellular calcium or by adding the calmodulin inhibitor trifluoperazine. These data indicate that in chief cells preincubated with cholera toxin, secretagogue induced increases in cell calcium concentration activate calmodulin thereby augmenting levels of cAMP and causing potentiation of pepsinogen secretion. Modulation of adenylate cyclase by changes in chief cell calcium concentration appears to be one mechanism whereby secretagogue interaction can result in potentiation of pepsinogen secretion. PMID- 3106348 TI - Aminoacetone oxidase from goat liver. Formation of methylglyoxal from aminoacetone. AB - An enzyme which oxidizes aminoacetone to methylglyoxal has been purified from the particulate fraction of goat liver. Polyamines, such as spermidine and spermine, are also good substrates for this enzyme. The pH optimum for aminoacetone oxidation was found to be 8.2. The apparent Km values of the enzyme for aminoacetone and spermidine were 0.009 and 0.095 mM, respectively. The subunit molecular weight of the enzyme was 93,000 as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The apparent molecular weight of the native enzyme was 186,000 by gel filtration. The enzyme is highly sensitive to carbonyl group reagents. The enzyme is not inhibited by monoamine and diamine oxidase inhibitors. PMID- 3106349 TI - [3H]forskolin. Direct photoaffinity labeling of the erythrocyte D-glucose transporter. AB - Irradiation of erythrocyte ghosts in the presence of [3H]forskolin resulted in a concentration-dependent, covalent incorporation of radiolabel into several of the major membrane protein bands. Most of the incorporation occurred in four regions of the gel. Peak 1 (216 kDa) was a sharp peak near the top of the gel in the region corresponding to spectrin. Peak 2 appeared to be associated with band 3 (89 kDa), while a third peak occurred around the position of band 4.2 (76 kDa). The fourth region of labeling was a broad area between 43-75 kDa which corresponds to the region of the glucose transporter. Forskolin labeling of this region was inhibited by cytochalasin B and D-glucose, but not L-glucose. Extraction of extrinsic membrane proteins resulted in a loss of radiolabeled protein from the 216- and 76-kDa regions. Treatment of membranes labeled with either cytochalasin B or forskolin with endo-beta-galactosidase resulted in identical shifts of the 43 to 75-kDa peaks to 42 kDa. Similarly, trypsinization of membranes photolabeled with either cytochalasin B or forskolin resulted in the generation of a 17-kDa radiolabeled fragment in both cases. Photoincorporation of [3H]cytochalasin B into the glucose transporter was blocked in a concentration dependent manner by unlabeled forskolin. PMID- 3106350 TI - Characterization of carrier-mediated transport systems for small neutral amino acids in human fibroblast lysosomes. AB - Analog inhibition studies of the uptake of proline, serine, and threonine into human fibroblast lysosomes, purified on Percoll gradients, reveal the presence of three new transport systems. These systems fail to show the Na+ requirement usual for the plasma membrane. Proline uptake into fibroblast lysosomes occurs mainly by two routes: a predominant route half-saturating at 0.01 mM, and a lower affinity route, half-saturating at 0.07 mM. The latter so far appears specific for L-proline and its 3,4-dehydro derivative. The high affinity route has a broad scope, recognizing best, beyond these two amino acids, various unbranched neutral amino acids not over 5 carbons long. Neither system accepts to a significant extent D-proline, hydroxyproline, cationic or anionic amino acids, nor neutral ones with bulky side chains. 2-Aminoisobutyrate and its N-methyl derivative have little effect on proline uptake, in contrast to their effectiveness on its uptake by the intact fibroblast. The rate of lysosomal proline uptake maximizes at about pH 6.4, is inversely related to the osmolarity of the medium, and is unaffected by the extralysosomal presence of MgATP. The competition among alanine, serine, and threonine points to sharing of the broad-scope system for proline, although the main part of their uptake occurs by a third route that rejects amino acids in which the alpha-amino group is methylated. PMID- 3106351 TI - Isolation of the DNA polymerase alpha core enzyme from mouse cells. AB - DNA polymerase alpha has been purified from mouse hybridoma cells approximately 30,000-fold using a combination of conventional and high performance liquid chromatography. In contrast to previous characterizations of mammalian DNA polymerase alpha, this enzyme has a single high molecular mass polypeptide (185 kDa) in tight association with a 68-kDa polypeptide and this structure appears to be the core DNA polymerase of the mouse cells. The biochemically purified enzyme, with a specific activity of approximately 200,000 units/mg protein, has an estimated molecular mass by gel filtration chromatography of 240 kDa and sedimentation value of 9 S, consistent with the enzyme being a heterodimer of 185 and 68 kDa. The enzyme is sensitive to both N-ethylmaleimide and aphidicolin and insensitive to ddTTP. Using an activated DNA template, the apparent Km values for the deoxynucleotide triphosphates are approximately 0.5-1 microM. The purified DNA polymerase has neither exonuclease nor primase activities and is the predominant DNA polymerase alpha activity in the mouse cells. PMID- 3106352 TI - Phosphatidylethanolamine biosynthesis in rat mammary carcinoma cells that require and do not require ethanolamine for proliferation. AB - Epithelial cells and some of their transformed derivatives require ethanolamine to grow normally in defined culture medium. When these cells are cultured without ethanolamine, the amount of cellular phosphatidylethanolamine is considerably reduced. Using a set of rat mammary carcinoma cell lines whose growth is responsive (64-24 cells) and not responsive (22-1 cells) to ethanolamine, the biochemical mechanism of ethanolamine responsiveness was investigated. The biosynthesis and metabolism of phospholipid, particularly of those involving phosphatidylethanolamine, were thus compared between the two types of cells. The incorporation of [3H]serine into phosphatidylserine and phosphatidylethanolamine in 64-24 cells was 60 and 37%, respectively, of those in 22-1 cells. However, the activity of phosphatidylserine decarboxylase was virtually the same in these cell lines. When these cells were cultured in the presence of [32P]phosphatidylcholine and [32P]phosphatidylethanolamine, the rate of accumulation of 32P-labeled phosphatidylserine from the radioactive phosphatidylethanolamine was considerably reduced in 64-24 cells compared to that in 22-1 cells, although the rate of synthesis of phosphatidylserine and phosphatidylethanolamine from the radioactive phosphatidylcholine was similar between the two cell lines. The rate of labeling phosphatidylcholine from the radioactive phosphatidylethanolamine was also reduced in 64-24 cells, although the difference was not as great as that of phosphatidylserine. Incorporation of 32P into phosphatidylethanolamine was correlated with the concentration of ethanolamine in the culture medium in 64-24 cells, whereas in 22-1 cells the incorporation was not influenced by ethanolamine. Enzyme activities of the CDP-ethanolamine pathway were not significantly different between the two cell lines. The rate of degradation of phosphatidylethanolamine was also similar in these cell lines. These results show that ethanolamine responsiveness of 64-24 cells, and probably other epithelial cells, is due to a limited ability to synthesize phosphatidylserine resulting from a limited base-exchange activity utilizing phosphatidylethanolamine. PMID- 3106353 TI - Quantitative studies of hydroperoxide reduction by prostaglandin H synthase. Reducing substrate specificity and the relationship of peroxidase to cyclooxygenase activities. AB - The peroxidase activity of prostaglandin H (PGH) synthase catalyzes reduction of 5-phenyl-4-pentenyl hydroperoxide to 5-phenyl-4-pentenyl alcohol with a turnover number of approximately 8000 mol of 5-phenyl-4-pentenyl hydroperoxide/mol of enzyme/min. The kinetics and products of reaction establish PGH synthase as a classical heme peroxidase with catalytic efficiency similar to horseradish peroxidase. This suggests that the protein of PGH synthase evolved to facilitate peroxide heterolysis by the heme prosthetic group. Comparison of an extensive series of phenols, aromatic amines, beta-dicarbonyls, naturally occurring compounds, and nonsteroidal anti-inflammatory drugs indicates that considerable differences exist in their ability to act as reducing substrates. No correlation is observed between the ability of compounds to support peroxidatic hydroperoxide reduction and to inhibit cyclooxygenase. In addition, the resolved enantiomers of MK-410 and etodolac exhibit dramatic enantiospecific differences in their ability to inhibit cyclooxygenase but are equally potent as peroxidase-reducing substrates. This suggests that there are significant differences in the orientation of compounds at cyclooxygenase inhibitory sites and the peroxidase oxidation site(s). Comparison of 5-phenyl-4-pentenyl hydroperoxide reduction by PGH synthase and horseradish peroxidase reveals considerable differences in reducing substrate specificity. Both the cyclooxygenase and peroxidase activities of PGH synthase inactivate in the presence of low micromolar amounts of hydroperoxides and arachidonic acid. PGH synthase was most sensitive to arachidonic acid, which exhibited an I50 of 0.6 microM in the absence of all protective agents. Inactivation by hydroperoxides requires peroxidase turnover and can be prevented by reducing substrates. The I50 values for inactivation by 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid are 4.0 and 92 microM, respectively, in the absence and presence of 500 microM phenol, a moderately good reducing substrate. The ability of compounds to protect against hydroperoxide induced inactivation correlates directly with their ability to act as reducing substrates. Hydroquinone, an excellent reducing substrate, protected against hydroperoxide-induced inactivation when present in less than 3-fold molar excess over hydroperoxide. The presence of a highly efficient hydroperoxide-reducing activity appears absolutely essential for protection of the cyclooxygenase capacity of PGH synthase. The peroxidase activity is, therefore, a twin-edged sword, responsible for and protective against hydroperoxide-dependent inactivation of PGH synthase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3106354 TI - Early steps initiating a degradation pathway in Escherichia coli. Characterization of the first intermediate. AB - Our previous studies demonstrated that a site-specific cleavage event initiates the degradation of large premature termination polypeptides of beta-galactosidase in Escherichia coli. We have isolated the first cleavage intermediate, the "B" polypeptide, by elution from sodium dodecyl sulfate-polyacrylamide gels. The NH2 terminus of this protein, determined by automated Edman degradation, was that of the wild-type molecule and thus established that the first cleavage event was at the COOH-terminal end. The sequence of the COOH-terminal end of the B polypeptide was determined by using the enzyme carboxypeptidase Y. Direct assignment of COOH terminal residues was made by using o-phthaldialdehyde derivatization and the stoichiometry confirmed by a double-label analysis. The COOH-terminal end of the B polypeptide is at position 837 in the beta-galactosidase sequence. If a single endoproteolytic cleavage event was responsible, the cleavage would have occurred between 2 threonine residues (at positions 837 and 838) that are located within a hydrophobic domain. We have observed other covalent modifications that precede the appearance of the B polypeptide, but these do not appear to participate in signaling the first cleavage event. The structure of the COOH-terminal end of B suggests a high degree of specificity by the initial cleavage enzyme. We propose that this unique site serves as a specific signal and that exposure of this site to the specific cleavage enzyme controls the event initiating the degradation pathway. PMID- 3106355 TI - Regulation of insulin receptor internalization in vascular endothelial cells by insulin and phorbol ester. AB - Phorbol 12-myristate 13-acetate (PMA) was used to examine the role of insulin receptor phosphorylation in the regulation of insulin receptor internalization in vascular endothelial cells. Association of 125I-insulin in rat capillary and bovine aortic endothelial cells preincubated with PMA was increased by 80 and 64% over control, respectively. The increase was due to enhanced 125I-insulin internalization as opposed to an effect on surface-bound hormone. PMA had no significant effect on 125I-insulin degradation or on release of internalized insulin from the cells. Internalization of 125I-labeled insulin receptor was determined by the resistance of labeled receptor to trypsinization. At 10 degrees C, nearly all of the labeled receptor was sensitive to removal by trypsin, indicating that it was exposed on the cell surface. Exposure of labeled cells to insulin (100 nM) at 37 degrees C resulted in the rapid appearance of trypsin resistant insulin receptor, indicating receptor internalization. Steady state for receptor internalization was attained at 10-15 min. When surfaced-labeled cells were preincubated with PMA at 37 degrees C, the rate of insulin receptor internalization was increased by 3.6 +/- 0.2-fold and 2.1 +/- 0.5-fold at 1 and 5 min of insulin exposure, respectively (ED50 at 16 nM PMA). This effect of PMA was associated with an increase in serine phosphorylation of the insulin receptor. Thus, PMA increased insulin internalization in the endothelial cells by modulating the insulin-induced internalization of the receptor. The additive effects of PMA and insulin on insulin receptor phosphorylation suggest that the phorbol ester and insulin act via independent signaling mechanisms. PMID- 3106356 TI - Substrate specificities of rat kidney lysosomal and cytosolic alpha-D mannosidases and effects of swainsonine suggest a role of the cytosolic enzyme in glycoprotein catabolism. AB - Swainsonine is a potent inhibitor of lysosomal alpha-D-mannosidase, causes the production of hybrid glycoproteins, and is reported to produce a phenocopy of hereditary alpha-mannosidosis. We now report that the effects of swainsonine administration in the rat are different in two respects from those found in other animals thus far studied. Swainsonine caused the accumulation of oligosaccharide in kidney and urine but not in liver or brain. The accumulated oligosaccharides were mainly Man(alpha 1-3)[Man(alpha 1-6)]Man(beta 1-4)GlcNAc, Man(alpha 1 3)[Man(alpha 1-6)[Man(alpha 1-3)]Man(beta 1-4) GlcNAc, and Man(alpha 1 3)[Man(alpha 1-6)]Man(alpha 1-6)[Man(alpha 1-3)]Man(beta 1-4)GlcNAc. Analogous branched Man4 and Man5 structures are found in pig and sheep tissues, but they are N, N'-diacetylchitobiose derivatives. The substrate specificities of rat kidney lysosomal and cytosolic alpha-D-mannosidases were investigated because in one type of hereditary alpha-mannosidosis, that occurring in man, the major storage products are linear rather than branched oligosaccharides. The lysosomal enzyme showed much greater activity toward linear oligosaccharides than toward the branched oligosaccharides induced in the kidney by swainsonine. On the other hand, cytosolic alpha-D-mannosidase preferred the branched oligosaccharides, a result suggesting that this mannosidase might be inhibitable by swainsonine and that the enzyme might play a normal role in glycoprotein catabolism. Swainsonine was indeed found to inhibit this enzyme at relatively high concentrations (I50 at 100 microM swainsonine), and concentrations of this magnitude were in fact found in the cytosol of kidney of swainsonine-fed rats. The kidney cytosolic alpha-D mannosidase levels were reduced in these rats and, more important, the accumulated oligosaccharides were present mainly in the cytosol rather than in lysosomes. These results point to possible involvement of cytosolic alpha-D mannosidase in glycoprotein degradation in the rat. PMID- 3106357 TI - CO2 adducts as reactive analogues of carboxylate substrates for aconitase and other enzymes of carbohydrate metabolism. AB - The CO2 adducts resulting from N-, O-, and S-carboxylation of suitable precursors are close analogues of carboxylate substrates in which -NH-CO2-, -O-CO2-, or -S CO2- replaces -CH2-CO2- in the physiological substrate, -NOH-CO-2 replaces -CHOH CO-2 and O-CO2- replaces -O-PO3H- R-XH + CO2 in equilibrium with R-X-CO2- + H+ X( XH = -NH2, -NHOH, -OH or -SH). We find that aconitase catalyzes the CO2-dependent dehydration of N-hydroxy-DL-aspartate and erythro-beta-hydroxyl-L-aspartate with respective kcat values 62 and 90% of kcat for citrate and Km values of 3.6 and 3.2 mM, respectively. The CO2 adducts (carbamates) of the precursors would be structural and stereo analogues of the physiological substrate isocitrate. Detailed kinetic analyses of the behavior of intermediates and products show that aconitase catalyzes the formation of the enzyme-bound CO2 adducts from enzyme bound precursors and CO2 and directs them, as well as the preformed CO2 adducts, into alpha,beta water elimination reactions formally identical to the isocitrate/cis-aconitate reaction. Six other enzymes of carbohydrate metabolism (succinate thiokinase and isocitrate, glucose-6-phosphate, succinate semialdehyde, glutamate, and malate dehydrogenase) utilize CO2 adducts as reactive substrate analogues. At least one of these (glucose-6-phosphate dehydrogenase) catalyzes the formation of the enzyme-bound CO2 adduct (presumed to be D-glucose 6-carbonate in this case) from enzyme-bound precursor (D-glucose) and CO2 in the manner of aconitase. The case of malate dehydrogenase is unique because the reactive malate analogue, -O2C-O-CHOH-CO-2, arises from nucleophilic attack of HCO-3 on the carbonyl of glyoxylate, rather than electrophilic attack of CO2 on the hydrated carbonyl of glyoxylate. PMID- 3106358 TI - Diacylglycerol increases cytosolic free Ca2+ concentration in rat pituitary cells. Relationship to thyrotropin-releasing hormone action. AB - To elucidate possible functions of elevation of endogenous diacylglycerol induced by thyrotropin-releasing hormone in pituitary cells, we have studied the actions of two synthetic diacylglycerols, sn-1-oleoyl-2-acetylglycerol (OAG) and sn-1,2 dioctanoylglycerol (DiC8), on cytosolic free calcium concentration ([Ca2+]i) in GH4C1 cells. OAG induced an immediate increase in [Ca2+]i which gradually reached a peak that was twice the basal level after the first min; [Ca2+]i then returned to remain at basal level after 3 min. The increase in [Ca2+]i was dependent on the concentration of OAG added with two apparent potencies; half-maximal actions on [Ca2+]i were observed at 70 nM and greater than 20 microM. The increase in [Ca2+]i induced by OAG was blocked completely by chelating extracellular calcium, or by pretreatment with calcium channel blockers. The phorbol ester 12-O tetradecanoylphorbol-13-acetate, which itself induces a rise in [Ca2+]i in these cells that is similar in time course, magnitude, and drug sensitivity to that of OAG, blocked completely the actions of subsequent exposure to OAG. Analogous results were obtained using DiC8, although DiC8 induced a transient inhibition to 75% of basal levels of [Ca2+]i after the initial increase in [Ca2+]i, and DiC8 was less potent than OAG. These data indicated that diacylglycerols induce influx of extracellular calcium in these cells, possibly by activation of voltage dependent Ca2+ channels. Furthermore, diacylglycerols and phorbol esters appear to utilize a common pathway in eliciting these actions on [Ca2+]i, possibly involving activation of a protein kinase C. These actions of diacylglycerol provide a pathway by which thyrotropin-releasing hormone may act to enhance calcium channel activity. PMID- 3106359 TI - Cloning of the gene encoding a catalytically self-sufficient cytochrome P-450 fatty acid monooxygenase induced by barbiturates in Bacillus megaterium and its functional expression and regulation in heterologous (Escherichia coli) and homologous (Bacillus megaterium) hosts. AB - In a previous publication (Narhi, L. O., and Fulco, A. J. (1986) J. Biol. Chem. 261, 7160-7169) we described the characterization of a 119,000-dalton P-450 cytochrome that is strongly induced by barbiturates in Bacillus megaterium. In the presence of NADPH and O2, this single polypeptide can catalyze the hydroxylation of long-chain fatty acids without the aid of any other protein. The gene encoding this unique monooxygenase (cytochrome P-450BM-3) has now been cloned by an immunochemical screening technique. The Escherichia coli clone harboring the recombinant plasmid produces a 119,000-dalton protein that appears to be electrophoretically and immunochemically identical to the B. megaterium enzyme and contains the same N-terminal amino acid sequence. The recombinant DNA product also exhibits the characteristic cytochrome P-450 spectrum and is fully functional as a fatty acid monooxygenase. In E. coli, the synthesis of P-450BM-3 is directed by its own promoter included in the DNA insert and proceeds constitutively at a very high rate but is not stimulated by pentobarbital. However, when the cloned P-450BM-3 gene, either intact or in a truncated form, is introduced back into B. megaterium via an E. coli/Bacillus subtilis shuttle vector, its expression is constitutively repressed but is induced by pentobarbital. This finding demonstrates that the regulatory region of the P 450BM-3 gene that responds to barbiturates is included in the cloned DNA. The evidence also indicates that pentobarbital cannot directly act on the gene to cause induction but presumably interacts with another component such as a repressor molecule that is present in B. megaterium but is absent in the E. coli clone. PMID- 3106360 TI - Identification and characterization of two functional domains in cytochrome P 450BM-3, a catalytically self-sufficient monooxygenase induced by barbiturates in Bacillus megaterium. AB - In a previous publication (Narhi, L. O. and Fulco, A. J. (1986) J. Biol. Chem. 261, 7160-7169) we described the characterization of a soluble 119,000-dalton P 450 cytochrome (P-450BM-3) that was induced by barbiturates in Bacillus megaterium. This single polypeptide contained 1 mol each of FAD and FMN/mol of heme and, in the presence of NADPH and O2, catalyzed the oxygenation of long chain fatty acids without the aid of any other protein. We have now utilized limited trypsin proteolysis in the presence of substrate to cleave P-450BM-3 into two polypeptides (domains) of about 66,000 and 55,000 daltons. The 66-kDa domain contains both FAD and FMN but no heme, reduces cytochrome c in the presence of NADPH, and is derived from the C-terminal portion of P-450BM-3. The 55-kDa domain is actually a mixture of three discrete peptides (T-I, T-II, and T-III) separable by high performance liquid chromatography. All three contain heme and show a P 450 absorption peak in the presence of CO and dithionite. The major component, T I (Mr = 55 kDa), binds fatty acid substrate and has an N-terminal amino acid sequence identical to that of intact P-450BM-3, an indication that this domain constitutes the N-terminal portion of the 119-kDa protein. T-II (54 kDa) is the same as T-I except that it is missing the first nine N-terminal amino acids and does not bind substrate. T-III (Mr = 53.5 kDa) has lost the first 15 N-terminal residues and does not bind substrate. Since trypsin digestion of P-450BM-3 carried out in the absence of substrate yields T-II and T-III but no T-I, it appears that 1 or more residues of the first nine N-terminal amino acids of this protein are intimately involved in substrate binding. Although both the heme- and flavin-containing tryptic peptides retain their original half-reactions, fatty acid monooxygenase activity cannot be reconstituted after proteolysis, and the two domains, once separated, show no affinity for each other. In most respects, the reductase domain of P-450BM-3 more closely resembles the mammalian microsomal P-450 reductases than it does any known bacterial protein. PMID- 3106361 TI - Stimulation of epidermal growth factor receptor threonine 654 phosphorylation by platelet-derived growth factor in protein kinase C-deficient human fibroblasts. AB - We have tested the hypothesis that the mechanism of platelet-derived growth factor (PDGF) and phorbol diester action to decrease the apparent affinity of the epidermal growth factor (EGF) receptor is the phosphorylation of the EGF receptor at the Ca2+/phospholipid-dependent protein kinase (protein kinase C) phosphorylation site, threonine 654. Protein kinase C-deficient cells were prepared by prolonged incubation of human fibroblasts with phorbol diester. Addition of phorbol diesters to these cells fails to regulate EGF receptor affinity or threonine 654 phosphorylation. In contrast, PDGF treatment of both control and protein kinase C-deficient fibroblasts causes a decrease in the apparent affinity of the EGF receptor and an increase in threonine 654 phosphorylation. Thus, the ability of PDGF or phorbol diester to modulate EGF receptor affinity occurs only when threonine 654 phosphorylation is increased. The stoichiometry of threonine 654 phosphorylation associated with a 50% decrease in the binding of 125I-EGF to high affinity sites was 0.15 versus 0.3 mol of phosphate per mole of EGF receptor when 32P-labeled fibroblasts are treated with PDGF or phorbol diester, respectively. It is concluded that EGF receptor phosphorylation at threonine 654 can be regulated by PDGF independently of protein kinase C, substoichiometric phosphorylation of the total EGF receptor pool at threonine 654 is caused by maximally effective concentrations of PDGF, and different extents of phosphorylation of EGF receptors at threonine 654 are observed for maximally effective concentrations of PDGF and phorbol diester, respectively. The data are consistent with the hypothesis that a specific subpopulation of EGF receptors that exhibit high affinity for EGF are regulated by threonine 654 phosphorylation. PMID- 3106364 TI - [Absorbable synthetic clips and pulmonary excision. Our clinical experience]. AB - Analysis of the first 50 clinical cases confirmed conclusions of experimental studies in large animals with respect to the use of absorbable synthetic clips formed of lactomer and polydioxanone. The advantages of clips when compared with ligatures include rapidity and simplicity of use and ease of insertion, even in regions difficult to approach surgically with the fingers. The advantages of clips of the absorbable synthetic type over conventional metallic material are: safety and reliability due to their locking system and the conservation of sufficient residual resistance, improved behavior in biologic media, radio transparency and total inertia in magnetic fields compatible with postoperative radiation and modern medical imaging procedures (CT scan, IRM), and finally progressive resorption predictable by simple hydrolysis and then total disappearance after 6 to 7 months. With staplers of the TA and GIA type these clips make sutures and ligatures during lung resection surgery entirely automatic. PMID- 3106362 TI - Cytochrome P-450 and NADPH-cytochrome P-450 reductase are degraded in the autolysosomes in rat liver. AB - We have investigated the degradation in rat liver of two typical endoplasmic reticulum (ER) membrane proteins, phenobarbital (PB)-inducible cytochrome P-450 (P-450[PB]) and NADPH-cytochrome P-450 reductase (FP2). Autolysosomes, almost completely free from contamination by the other organelles such as ER, were prepared from leupeptin-treated rat livers according to the method of Furuno et al. (Furuno, K., T. Ishikawa, and K. Kato, 1982, J. Biochem., 91:1943-1950). Quantitative immunoblot analysis showed that these two proteins were found in large amounts in the autolysosomes regardless of PB treatment. The specific content of P-450 (PB) in the autolysosomes changed along with that in the microsomes during and after PB treatment, whereas hardly any P-450(PB) was detected in the cytosol fraction throughout the experiment. We also found a marked increase in the autolysosomal proteins 3 d after cessation of PB treatment when microsomal proteins are degraded most rapidly. Ferritin immunoelectron microscopy revealed directly that when the limiting membranes of the premature autolysosomes were partially broken the smooth vesicles segregated within the autolysosomes were heavily stained with ferritin anti-P-450(PB) conjugates. Thus, for the first time, we could present convincing evidence that P-450(PB) and FP2 are segregated to be degraded in the autolysosomes. PMID- 3106365 TI - [Congenital diverticulum of the lower choledochus. Apropos of a case with intraduodenal development]. AB - The onset of subicterus in a patient revealed the presence of a congenital diverticulum of lower common bile duct of intraduodenal development. A part from the rarity of this lesion this case is of interest due to the complete range of ultrasound, endoscopic and CT scan imaging performed, the association of a common mesentery and the surgical technique employed. The latter comprised exeresis by transduodenal approach and a side-to-side choledocho-duodenal anastomosis through the intermediary of the diverticular sleeve. The nosology and differential diagnosis of diverticulum of lower common bile duct are discussed and data from a literature review used to describe diagnostic, etiopathogenic and histopathologic aspects as well as complications and treatment of this type of congenital dilatation of lower biliary tract. PMID- 3106363 TI - Plasminogen activator and mouse spermatozoa: urokinase synthesis in the male genital tract and binding of the enzyme to the sperm cell surface. AB - When ejaculated mouse spermatozoa were embedded in a plasminogen-containing insoluble protein substrate, a zone of proteolysis developed progressively, centered around the sperm head region. Lysis did not occur in absence of plasminogen or in presence of antibodies against the urokinase-type plasminogen activator (u-PA). Zymographic and immunological analyses confirmed the presence of u-PA in extracts of ejaculated mouse spermatozoa. In contrast, the u-PA activity of sperm cells obtained from testis or from vas deferens was low, although these cells were able to bind added murine u-PA. The sites of u-PA synthesis were identified by measuring u-PA activity and u-PA mRNA content in protein extracts and in total RNA preparations of various portions of the male genital tract. The highest levels of u-PA activity and of u-PA mRNA were found in vas deferens and seminal vesicles. The cells that synthesize u-PA were localized by hybridizing frozen sections of various portions of the genital tract to a u-PA cRNA probe. In all tissues examined, u-PA mRNA was predominantly located in the epithelial layer, and the strongest signal was observed over that of the vas deferens. Hence, the u-PA associated with ejaculated sperm cells is probably acquired from genital tract secretions. Sperm-bound u-PA may participate in the proteolytic events that accompany capacitation and fertilization. PMID- 3106366 TI - [Congenital diverticulum of the bile ducts. Apropos of a case and review of the literature]. AB - The authors report a case of Congenital Diverticulum of the common bile duct treated by surgery. Literature reviews are giving detailed reports on this rare affection which falls within the scope of Congenital Diverticulum of the common bile duct, it has only a small share in this report. The comments relate the anatomic, pathogenic, diagnostic and evolutive data. The treatment appears to be possible in any case: surgical exeresis of the diverticulum. PMID- 3106368 TI - Hypoglycemia: factitious or felonious? PMID- 3106369 TI - The temporomandibular joint syndrome. PMID- 3106367 TI - Catastrophic health insurance. PMID- 3106370 TI - Pathophysiology of Graves' disease. PMID- 3106371 TI - Management of gastroesophageal reflux: an algorithm. PMID- 3106372 TI - Hyperalimentation: primary therapy for IBD? PMID- 3106374 TI - Cyclosporine: a double-edged sword. PMID- 3106373 TI - New approaches to management of colorectal carcinoma. PMID- 3106375 TI - Carlos J. Finlay: the mosquito man. PMID- 3106376 TI - An 8-year history of pulmonary emboli, deep-vein thrombosis. PMID- 3106377 TI - 'Normal' vs. physiologic saline. PMID- 3106378 TI - Hemochromatosis: gene frequency and Fe feeding. PMID- 3106379 TI - Respiratory distress in man with prosthetic valve. PMID- 3106380 TI - Atypical pneumonia and an unexpected pathogen. PMID- 3106381 TI - Clinical cognition 101. PMID- 3106382 TI - Supraventricular tachycardia after coronary bypass surgery. PMID- 3106383 TI - The genetics of diabetes. PMID- 3106384 TI - Differential diagnosis of jaundice. PMID- 3106385 TI - Quantitative high-performance liquid chromatographic analysis of Dabsyl-amino acids within 14 min. PMID- 3106386 TI - High-efficiency preparative-scale reversed-phase high-performance liquid chromatographic purification of 14C-labelled antibiotics. AB - The 14C-labelled antibiotics [2-14C]mupirocin, and [thienyl-3-14C]temocillin cannot be satisfactorily purified on a small scale by conventional methods of chromatography or recrystallisation. Their purification was successfully achieved by high-efficiency preparative-scale reversed-phase high-performance liquid chromatography. The purifications employed 250 mm X 10 mm I.D. or 22 mm I.D. stainless-steel columns packed with Merck LiChrosorb RP-18 (10 microns) stationary phase which were eluted with aqueous buffer solutions at flow-rates of 10-25 ml min-1 using conventional analytical instrumentation. PMID- 3106387 TI - Improvement of chemical analysis of antibiotics. IX. A simple method for residual tetracyclines analysis in honey using a tandem cartridge clean-up system. AB - A simple, rapid and precise analytical method for the residual tetracyclines in honey has been established using a tandem cartridge clean-up system (prepacked reversed-phase and ion-exchange cartridges) followed by high-performance liquid chromatography. The recoveries of oxytetracycline (OTC), tetracycline (TC), chlortetracycline (CTC) and doxycycline (DC) from honey spiked at a level of 1.0 ppm are 87.1, 85.3, 98.0 and 99.0%, respectively, with coefficients of variation of 1.1-3.9%. The detection limits in honey are 0.02 ppm for OTC and TC, and 0.05 ppm for CTC and DC, respectively. The time required for the analysis of four samples is only 1 h. PMID- 3106388 TI - Rapid determination of disaccharides from chondroitin and dermatan sulphates by high-performance liquid chromatography. PMID- 3106389 TI - Separation and characterization of high-density lipoprotein subpopulations by gel permeation chromatography. AB - High-density lipoproteins (HDL) contain at least five distinct subpopulations when analyzed by gradient gel electrophoresis. This report represents the first description of a simple technique for isolating these subpopulations of HDL in quantities sufficient to enable characterization in terms of particle size, apolipoprotein AI and apolipoprotein AII content and chemical composition. Lipoproteins were separated and subfractionated on a column of Superose 6B using a fast protein liquid chromatography system. Five normal subjects were studied: HDL2b and HDL3a were isolated as essentially single subpopulations from all subjects, while HDL2a could be isolated from only three of the subjects. HDL3b was isolated in a relatively impure form (70%) from all subjects. Identical subpopulations were identified in each subject by gradient gel electrophoresis of unseparated HDL. PMID- 3106390 TI - Anion-exchange fast protein liquid chromatographic characterization and purification of apolipoproteins A-I, A-II, C-I, C-II, C-III0, C-III1, C-III2 and E from human plasma. AB - This paper describes a procedure for the rapid isolation of urea-soluble apolipoproteins (apo) from delipidated human very-low- and high-density lipoproteins using anion-exchange fast protein liquid chromatography. The separation was complete within 30 min and peaks corresponding to apolipoproteins A-I, A-II, C-I, C-II, C-III0, C-III1, C-III2 and E were identified by comparing their chromatographic, electrophoretic and immunological behaviour with that of purified standards of each protein. A second purification step is necessary to obtain pure apolipoproteins. Apo E, which is difficult to purify by conventional chromatography, has been obtained in a good yield. The apo C-II that was obtained produced a symmetrical peak on chromatography but three bands in isoelectric focusing. The method can be upgraded to a preparative scale and offers the possibility of direct purification of apolipoproteins both from high-density lipoproteins and (following preliminary gel chromatography) from very-low-density lipoproteins. PMID- 3106391 TI - Gas chromatographic technique to simultaneously quantitate the gases produced by intestinal microorganisms from fermentation mixtures. PMID- 3106392 TI - Gas chromatographic method for the measurement of sodium valproate utilization by kidney tubules. PMID- 3106393 TI - Serum bioactive and immunoreactive follicle-stimulating hormone levels and the response to clomiphene in healthy young and elderly men. AB - Testicular function declines with normal aging, while serum immunoreactive LH and FSH levels increase. Since there are reports of an age-related decrease in the ratio of bioactivity to immunoreactivity (B/I ratio) for LH, we used a newly available bioassay for FSH to assess age-associated changes in the bioactivity and B/I ratio of FSH in man. Thirty-nine healthy men (23 young and 16 elderly) had single blood samples drawn. In addition, a subset of these men (12 young and 13 elderly) underwent frequent blood sampling for 24 h, both before and after 7 days of clomiphene citrate (CC) administration. Hourly blood samples from the 24 h sampling were pooled, and these, along with the single samples, were assayed for FSH by an in vitro bioassay system, using estrogen production by immature rat granulosa cells as the end point, and by RIA. Baseline single sample mean FSH, as measured by bioassay, was similar in young and elderly men [386 +/- 98 (+/- SEM) and 342 +/- 77 ng/mL, respectively]. Baseline mean FSH, measured by RIA, was significantly higher (P less than 0.001) in elderly men (234 +/- 31 ng/mL) than in young men (122 +/- 12 ng/mL). The baseline FSH B/I ratio based on single sampling was significantly lower (P less than 0.01) in elderly men (1.4 +/- 0.2) than in young men (2.7 +/- 0.3). In the men given CC and sampled for 24 h, mean bioactive FSH levels increased significantly in both the young (1180 +/- 282 ng/mL) and the elderly (992 +/- 227 ng/mL; P less than 0.01 for both values compared to baseline). Mean FSH by RIA also increased to similar levels in these young (217 +/- 34 ng/mL) and elderly (258 +/- 45 ng/mL) men. The FSH B/I ratio was 4.8 +/- 0.8 in young and 4.7 +/- 1.1 in elderly men after CC administration. We conclude that serum bioactive FSH levels are similar in elderly and young men, suggesting that the age-related decline in testicular function in man cannot be explained by a chronic deficiency in FSH stimulation; elderly men have a lower serum FSH B/I ratio than young men, which may reflect changes in the circulating form of FSH with aging; and administration of CC to young and elderly men increases both bioactive and immunoreactive serum FSH, implying preserved hypothalamic-pituitary responsiveness in the elderly. PMID- 3106394 TI - Hormonal dynamics during luteal-follicular transition. AB - To gain insights into the neuroendocrine basis for the initiation of folliculogenesis, the hormonal dynamics during the period from the late luteal to the early follicular phase of the menstrual cycle (the luteal-follicular transition) were examined. Blood samples were obtained at 2-h intervals for 5 consecutive days in seven women and at 15-min intervals for 8 h on each of 4 consecutive days in five women. The results indicate that the luteolytic process, as reflected by an exponential decline of both serum estradiol and progesterone levels, began at least 64 h before the onset of menses. During estradiol and progesterone withdrawal, there was a selective increase in mean serum FSH levels (P less than 0.001) beginning 24 h before and reaching a peak 24 h after the onset of menses. The frequency of LH pulses increased slightly but not significantly during this period, with a significant rise in mean serum LH levels on the day of menses. Thus, an acute rise in FSH concentrations the day before and in LH concentrations the day after the onset of menses occurs during luteal follicular transition. The dissociation of FSH and LH secretion observed suggests that additional neuroendocrine events other than changes in pulsatile GnRH secretion may be operative during this period. These findings indicate that the initiation of folliculogenesis for the ensuing cycle occurs during the late luteal phase by a process of selective augmentation in FSH secretion independent of hypothalamic GnRH secretion. This event may ultimately prove to be a manifestation of the action of recently characterized ovarian peptides on FSH secretion. PMID- 3106395 TI - Variable androgen receptor levels in infertile men. AB - Labeled methyltrienelone was used to determine androgen receptor (AR) levels in cultured pubic skin fibroblasts in 40 infertile men with primary seminiferous tubule disorders and 18 normal men. LH pulse patterns and mean serum LH levels were also determined by blood sampling at 10-min intervals for 6 h. The infertile men and the normal men had similar mean receptor levels [mean, 28.1 +/- 2.0 (+/- SEM) and 24.8 +/- 1.8 fmol/mg protein, respectively]. However, 5 men with chromosomal disorders had a higher mean AR level (41.3 +/- 6.2 fmol/mg protein) than the normal men, and 5 of the remaining infertile men (14.2%) had receptor levels that were less than the minimum value in normal men. In men with idiopathic oligospermia, 19.0% had low receptor levels. Although mean serum FSH and testosterone levels were similar in the infertile men with low AR levels and in the normal men, mean LH levels were significantly elevated in this group (7.1 vs. 3.6 IU/L), the higher values being a result of increased LH pulse amplitude (mean, 5.6 vs. 2.8 IU/L). The LH-testosterone product (an index of androgen resistance) was also elevated in these men. When infertile men with low AR levels were matched with infertile men with normal receptor levels, the mean LH values were significantly elevated in the former, as was the LH-testosterone product. Testosterone values were similar in the two groups of men. After excluding subjects with chromosomal disorders, there were no significant correlations between AR levels and other indices of androgen action, such as semen volume, seminal fructose, or sex hormone-binding globulin levels. We conclude that AR levels are higher in patients with severe testicular failure associated with X chromosome disorders. Also, AR defects were found in 19.0% of infertile men with idiopathic oligospermia. Finally, elevation of mean LH levels in men with seminiferous tubule disorders may reflect resistance to androgen action. PMID- 3106398 TI - Separate induction of MHC and thyroid microsomal antigen (McAg) expression on thyroid cell monolayers: enhancement of lectin-induced McAg expression by interferon-gamma. AB - Interferon-gamma (IFN gamma) induced the expression of the MHC class II antigens HLA-DR and -DQ on 1- to 2-week-old thyrocytes from normal thyroid tissue and thyroid tissue from patients with autoimmune thyroid disease; it also enhanced the expression of B2-microglobulin, which is associated with MHC class I molecules. However, the expression of thyroglobulin and thyroid microsomal antigen (McAg) was not detected after IFN gamma stimulation. Autologous and allogeneic peripheral blood mononuclear cells had the same ability as IFN gamma to induce antigen expression when cocultured with thyrocytes. In contrast, leucoagglutinin (LAG) induced McAg as well as HLA-DR and B2-microglobulin expression on thyrocytes, but not thyroglobulin expression. Concanavalin A and pokeweed mitogen also induced McAg expression. The time course of LAG induction of McAg was not always correlated with that of HLA-DR. Anti-IFN gamma, antiinterleukin-2 receptor, and anti-HLA-DR monoclonal antibodies inhibited LAG or peripheral blood mononuclear cell induction of HLA-DR expression, but not LAG induction of McAg expression. Anti-HLA-DR reduced the IFN gamma induction of HLA DR. INF gamma enhanced thyrocyte McAg expression induced by LAG, especially when thyrocytes were incubated with IFN gamma for 24 h before LAG stimulation. In contrast, in the absence of LAG stimulation, IFN gamma suppressed already present spontaneous McAg expression. TSH did not induce McAg and HLA-DR expression on DR negative thyrocytes, but enhanced weak DR expression induced by other stimulants, e.g. IFN gamma or lectins. These data suggest that in vitro induction mechanisms of MHC class I and II antigens and McAg are different; MHC antigens are induced by IFN gamma, whereas McAg is induced by lectin, probably acting on thyrocytes directly; and IFN gamma has an enhancing effect on LAG-induced thyrocyte McAg expression. PMID- 3106397 TI - Evidence for Leydig cell dysfunction in infertile men with a selective increase in plasma follicle-stimulating hormone. AB - Recent studies in acutely castrated males of several species have demonstrated that testosterone (T) alone, given in doses that produce normal plasma T levels, can maintain normal plasma FSH and LH levels. This suggests that a nonsteroidal factor from the seminiferous tubule is not required to regulate FSH release, and raises the possibility that Leydig cell function may not be fully normal in oligo or azoospermic men with increased plasma FSH levels. To clarify this, we studied T production rates in 11 sexually mature, infertile, but otherwise healthy men who had increased plasma FSH and normal plasma LH, T, and estradiol levels and in 9 normal men. Although individual plasma T and LH levels in the infertile men were within the normal ranges, the mean plasma T level of the infertile men was significantly lower (P less than 0.002), and the mean plasma LH level was significantly higher (P less than 0.002) than values in the normal men. The infertile men also had significantly lower plasma free T concentrations (P less than 0.005), while sex hormone-binding globulin and estradiol levels were similar to those of the normal men. The production rate of T in the infertile men was half that in the normal men (P less than 0.001). We conclude that T production is significantly reduced in infertile men who have a selective increase in plasma FSH. Because of the known role of Leydig cell sex steroids in the negative feedback control of FSH, this finding may explain the elevated plasma FSH concentrations characteristic of men with germ cell loss without the need to postulate a deficiency of a separate seminiferous tubule factor. PMID- 3106396 TI - Effects of increasing the frequency of low doses of gonadotropin-releasing hormone (GnRH) on gonadotropin secretion in GnRH-deficient men. AB - The effects of increasing the frequency of pulsatile GnRH administration on LH and FSH responsiveness were studied in five GnRH-deficient men who had achieved normal sex steroid levels during prior long term GnRH replacement. Intravenous doses of GnRH were employed that had previously been demonstrated to produce LH and FSH levels in each subject similar to those in normal men. Both acute and chronic changes in pituitary responses were studied after progressive increases in GnRH frequency (from every 120 to 60 min, from 60 to 30 min, and from 30 to 15 min) during three 12-h admissions, each separated by 7 days. During the two intervals between the studies GnRH frequency was 60 and 30 min, respectively. Pituitary responses were characterized by determining the mean serum LH and FSH levels, LH pulse amplitudes, and mean LH and FSH levels which were normalized for the frequency of GnRH administration (nLH and nFSH). As the frequency of GnRH stimulation was increased acutely, mean serum LH levels rose progressively, in contrast to both LH pulse amplitude and nLH levels which decreased, while serum testosterone (T) concentrations remained constant. No further evidence of gonadotroph desensitization occurred after chronic GnRH administration at either 60- or 30-min intervals. At higher frequencies of GnRH stimulation, discrete pulses of LH were not always apparent after injections of GnRH, and in two men, marked destabilization of the gonadotroph responses occurred. Even without detectable LH pulses, serum T levels did not decline during administration of GnRH at intervals as rapid as 15 min. In contrast, there was no change in mean FSH concentrations, although nFSH values decreased progressively as the GnRH frequency was increased. nFSH levels fell to a greater degree than nLH after each increase in GnRH frequency. Thus, pituitary gonadotroph responsiveness to a fixed dose of GnRH decreased as the frequency of GnRH stimulation increased. FSH responsiveness decreased to a greater degree than did LH. Gonadotropin secretory responses are destabilized at higher frequencies of GnRH administration. Pulsatile LH stimulation of the testes does not appear necessary to maintain T secretion. PMID- 3106399 TI - Short term administration of gonadotropin-releasing hormone analog to a patient with a testosterone-secreting ovarian tumor. AB - A GnRH superagonist, buserelin, was administered for 16 days to a postmenopausal woman with a testosterone-secreting ovarian tumor. Serum gonadotropin levels decreased by more than 70%, and serum testosterone fell by more than 50%. This short term study demonstrates that in these uncommon tumors androgen secretion is gonadotropin sensitive, and suggests that GnRH analogs may have therapeutic value in such patients. PMID- 3106401 TI - Post-marketing surveillance of oral contraceptives. AB - Problems arise in the post-market surveillance of the possible long-term effects of oral contraceptives. These drugs are taken by very large numbers of people, in various doses, types and duration. One aspect is considered in this paper, the effects on pregnancy of these drugs taken before conception. Retrospective case trial studies are described together with longitudinal studies on women from their first exposure to a specific oral contraceptive. The difficulties of this approach, the causes of bias, the effect of social habits, and the discontinuity of usage are debated. PMID- 3106400 TI - Membrane IgD-positive B cells of "low-IgD serum phenotype" individuals fail to secrete IgD and fail to shift to preferential lambda light-chain expression in vitro. AB - IgD production by short-term human peripheral blood mononuclear cell (PBM) cultures was studied to establish the in vitro correlates of low serum IgD expression. Cells of persons with less than 3 micrograms/ml IgD in the serum, referred to as the low-serum IgD phenotype (LISP), were analyzed. Advantage was taken of recently developed data on spontaneous IgD biosynthesis by human B cells and the observation that lambda light chains are preferentially expressed by IgD secreting cells in vitro. Initial analysis of an IgD serum distribution showed that all LISP sera contained low but detectable amounts of IgD, with a mean value of 0.85 microgram/ml; this figure was 30- to 35-fold lower than the mean of the majority of the population. LISP PBM contained normal numbers of IgD-positive B cells which displayed a normal intensity of IgD per cell using comparative analysis of mean channel fluorescence by cell flow cytometry. Several lines of evidence suggested that IgD-secreting cells could not be generated from LISP lymphocytes in vitro. Namely, it was found that no IgD immunoglobulin-containing cells were found among PBM of LISP persons; cell lysates enriched for the intracellular fraction by Triton X-114 phase separation showed low IgD in LISP cells despite "normal" amounts of IgD in membrane-enriched fraction preparations; there was no spontaneous IgD secretion by any LISP PBM cultures; and neither LISP sera nor cellular IgD preparations showed IgD lambda/kappa ratios greater than 1.0, indicative of the absence of the preferential lambda light-chain expression associated with secretion of IgD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106402 TI - Drugs used in ovulation induction. Safety of patient and offspring. AB - Data on the safety of agents used to induce ovulation in women are presented, with a special reference to the normality of children at birth and puberty. No overall increase in anomalies has been found after the use of clomiphene citrate. This drug has been given up to day 35 of pregnancy, and its safety in these circumstances requires further analysis. More studies will also be needed on offspring as they pass through puberty, to ensure there are no defects in their Mullerian system. No increase in anomalies has been noted after the use of human menopausal gonadotrophins (HMG). The onset of menstrual rhythms and other parameters in the offspring appear to be normal. No increase in various cancers has been identified following the use of clomiphene or HMG, although most treated women have yet to enter the high risk years. PMID- 3106403 TI - Follicular steroids in relation to oocyte development and human ovarian stimulation protocols. AB - Oocytes of pre-ovulatory follicles were collected by laparoscopy for in-vitro fertilization in 118 women. Patients were treated either during the natural cycle, or after induction of ovulation with clomiphene citrate, or with human menopausal gonadotrophin (HMG), or clomiphene citrate combined with HMG. The oestrogens (oestrone + oestradiol) and total aromatizable androgens (androstenedione, testosterone and dehydroepiandrosterone and its sulphate) were assayed in follicular fluids using an enzymatic method. The levels of progesterone, 17 alpha OH-progesterone, thromboxane, and prostaglandins (PGE2 and PGF2 alpha) were determined by radioimmunoassay. The best follicular fluid indicator of oocyte fertilization in vitro was the A/E ratio, which was less than 1 when the oocyte was fertilized in vitro and led to a pregnancy. The lowest value for the A/E ratio was obtained with spontaneous ovulation protocols. Regardless of oocyte development, the progesterone level was always greater than 2000 ng/ml, and the PGE2/PGF2 alpha ratio was greater than 1 in all stimulated cycles. Our investigations show that a combination of clomiphene citrate and HMG provides the best stimulation, on the basis of follicular fluid analysis and the outcome of fertilized oocytes. PMID- 3106404 TI - Endocrine and follicle characteristics of cycles with and without endogenous luteinizing hormone surges during superovulation induction with pulsatile follicle-stimulating hormone. AB - The induction of superovulation in women with human gonadotrophins may result in blockage of the endogenous luteinizing hormone (LH) surge, but the reasons for this are not known. Ten normally ovulating women with longstanding infertility volunteered for this study. They were treated with 225 IU follicle-stimulating hormone (FSH) daily s.c. in a pulsatile manner (28 IU every 3 h) starting on cycle day 2. Serum FSH and oestradiol levels increased and serum LH levels decreased significantly during the FSH treatment, as compared to their spontaneous cycles. Only five women displayed an LH surge during the FSH treatment. Serum FSH and LH levels during treatment were significantly lower and the number of follicles 12-15 mm in diameter and their total fluid volume was significantly greater in the cycles without an endogenous LH surge. Basal LH levels in the cycles without an LH surge increased soon after the end of the FSH treatment (cycle day 18), while FSH levels were still very low without any incremental tendency. These results suggest that a high number of small follicles may have a suppressive effect on both tonic and mid-cycle gonadotrophin secretion. Furthermore, the LH suppressive mechanism seems to be different from that of the FSH. PMID- 3106405 TI - Results of planned in-vitro fertilization programming through the pre administration of the oestrogen-progesterone combined pill. AB - The use of an oestrogen-progesterone combined pill permits the induction of ovulation in the absence of any developing follicle. Two treatments were compared. In the first, patients received no prior treatment before stimulation. In the second, combined oestrogen-progesterone treatment was given during approximately two menstrual cycles prior to stimulation. No differences between the two groups were found in relation to oocyte maturity, fertilization in vitro, cleavage, replacement and pregnancy. Fewer luteinizing hormone surges occurred in patients pre-treated with steroids. The utilization of the oestrogen-progesterone combined pill prior to induction of ovulation facilitates the forward planning of patients for in-vitro fertilization. PMID- 3106407 TI - Comparison of the Gono-Pak system with the candle extinction jar for recovery of Neisseria gonorrhoeae. AB - Maximum CO2 levels in the Gono-Pak system were obtained 2 h after activation, with a mean value of 1.5%. Although this is less than the 2 to 3% CO2 level obtained with the candle jar, Gono-Pak produced comparable recovery of Neisseria gonorrhoeae in 357 clinical specimens and stock cultures. Using adjustable CO2 incubators, we found the recovery at 1% CO2 to be comparable to that at 5%, whereas 10% CO2 was inhibitory. PMID- 3106406 TI - Production and characterization of monoclonal antibodies to toxic shock syndrome toxin 1 and use of a monoclonal antibody in a rapid, one-step enzyme-linked immunosorbent assay for detection of picogram quantities of toxic shock syndrome toxin 1. AB - Twenty-six hybridoma cell lines that produced monoclonal antibodies to toxic shock syndrome toxin 1 (TSST-1) were generated by immunizing mice with a highly purified preparation of TSST-1 and fusing their splenic lymphocytes with SP2/0-Ag 14 cells. One monoclonal antibody of the immunoglobulin G1 isotype, designated as PEC-1 10-2SCH, was selected for extensive study. The specificity of this antibody was determined by testing spent culture fluid filtrates of TSST-1- and non-TSST-1 producing strains of Staphylococcus aureus by sodium dodecyl sulfate polyacrylamide gel electrophoresis and enzyme-linked immunoelectrotransfer blot techniques. Monoclonal antibody PEC-1-10-2SCH was specific for TSST-1-producing strains of S. aureus, reacting with TSST-1 and two other proteins which appear to be unique to S. aureus strains that produce TSST-1. Monoclonal antibody PEC-1-10 2SCH was used in conjunction with polyclonal rabbit antibodies to TSST-1 in a rapid, one-step, sensitive, specific, and quantitative enzyme-linked immunosorbent assay. This assay was shown to be more sensitive, faster, and simpler to perform than previously described isoelectric focusing, immunodiffusion, and solid-phase radioimmunoassays for TSST-1. Monoclonal antibody PEC-1-10-2SCH was not reactive with Staphylococcus protein A under the conditions of the test. PMID- 3106408 TI - Comparison of the AMS gram-negative susceptibility flex panel GNS-V and agar disk diffusion for testing of Pseudomonas aeruginosa. AB - Sixty Pseudomonas aeruginosa isolates were tested by the agar disk diffusion, AMS Vitek GNS-V flex panel (Vitek Systems, Inc., Hazelwood, Mo.), and agar dilution methods. Although the results of aminoglycoside tests were satisfactory, those of piperacillin and cefoperazone by Vitek GNS-V (T2.05 program) were not acceptable. PMID- 3106409 TI - Alginate production by clinical nonmucoid Pseudomonas aeruginosa strains. AB - The slime material from a revertant nonmucoid variant, derived by serial passage of a heavily mucoid Pseudomonas aeruginosa strain isolated from a patient with bacteremia, was found to contain 16% uronic acids, 48.5% carbohydrates, 11% protein, and 2% lipids. Chromatographic analysis by ion exchange chromatography revealed that this extracellular material consisted of three fractions, one uronic acid fraction with properties similar to those of the alginate fraction of the parental strain and two other fractions consisting of neutral sugars and proteins in approximately a 5:1 ratio. In addition, the slime material from six other clinical macroscopic nonmucoid P. aeruginosa strains was found to contain alginate. These results demonstrate that alginate production in various amounts is a property shared by all P. aeruginosa strains. PMID- 3106410 TI - Atypical isolates of Brucella abortus from Canada and the United States characterized as dye sensitive with M antigen dominant. AB - A total of 41 Brucella isolates, examined by standard biotyping procedures, were found to be similar to Brucella abortus biovar 2 in dye sensitivity but had a dominant M antigen. Oxidative metabolic tests performed on 39 of the isolates confirmed them as B. abortus. Additional biochemical and bacteriophage susceptibility studies were performed on 35 of the isolates. The isolates had identical reactions in the various tests, except for one isolate which was resistant to lysis by all phage strains used. Two isolates were injected into guinea pigs and shown to be virulent. The isolates described in this study appear similar to atypical Brucella isolates previously reported in the United Kingdom and the United States and may form the basis of a new biovar, B. abortus biovar 10. PMID- 3106411 TI - Density profile of group B streptococci, type III, and its possible relation to enhanced virulence. AB - The buoyant densities of virulent and colonizing group B streptococci, type III, were determined by centrifugation of bacteria on a linear, hypotonic density gradient. A total of 28 strains were investigated. Eleven strains were obtained from blood cultures of babies with early-onset disease, and eight strains were isolated from the cerebrospinal fluid of babies with late-onset septicemia and meningitis. Nine colonizing strains were genital isolates from pregnant women subsequently giving birth to healthy children. In each strain the buoyant density was determined before and after neuraminidase treatment. All strains showed an increase in the buoyant density after enzymatic removal of sialic acid, and the density differences before and after desialylation were calculated. The mean values of these differences for blood, cerebrospinal fluid, and colonizing isolates were 23.4, 25.3, and 10.6 mg/ml, respectively. The mean value for the colonizing strains differed significantly from the mean value for each group of virulent strains. All colonizing strains banded singly in the gradient, whereas five of the virulent strains divided into two density populations. Extracts of the low-density cells produced markedly more dense immunoprecipitates with type antiserum than did extracts of the high-density bacteria. One double-banding strain was positive for R protein. After separation of the two density populations, this antigen was detected only in the low-density population. The results indicate that bacterial buoyant density is inversely related to the amount of capsular polysaccharide enveloping the cell and that a determination of the density profile of the bacteria may be used for discriminating strains with an increased pathogenic potential. PMID- 3106412 TI - DNA probes for detection and identification of Mycoplasma pneumoniae and Mycoplasma genitalium. AB - DNA probes specific for Mycoplasma pneumoniae and Mycoplasma genitalium were selected from genomic libraries prepared in pUC13. The 32P-labeled probes could detect, by dot blot hybridization, down to about 0.1 ng of the specific mycoplasma DNA or 10(5) CFU. Biotinylation of probe decreased the sensitivity of detection and produced nonspecific background reactions with nonhomologous DNAs. Sulfonation of probe yielded a similar level of sensitivity with less background. PMID- 3106413 TI - Attempted reduction of Abbott MS-2 false-susceptible errors for cefotaxime resistant Pseudomonas aeruginosa by medium modification. AB - Thirty-five modifications of Abbott MS-2 growth medium were evaluated in an attempt to reduce the high frequency of false-susceptible errors produced by the MS-2 system when testing resistant Pseudomonas aeruginosa against cefotaxime. A hypotonic modification with 0.1% KNO3 reduced the errors from 41 to 20% for 23 resistant isolates. All hypertonic modifications proved unsatisfactory. No modification reduced false-susceptible errors to acceptable clinical levels. PMID- 3106414 TI - Lymphocytic activation in peripheral blood and cerebrospinal fluid during the course of chronic relapsing experimental allergic encephalomyelitis. AB - A monoclonal antibody against the human interleukin-2 receptor (anti-Tac) has been found to cross-react with an antigen on the surface of guinea pig leucocytes. Cells marking with anti-Tac and with an anti-pan T cell monoclonal antibody have been quantitated in the peripheral blood and cerebrospinal fluid (CSF) of guinea pigs with chronic relapsing experimental allergic encephalomyelitis (CR-EAE). T cells account for about 90% of peripheral blood leucocytes in all animals whilst in the CSF, T cells are the major contributor only when there is a pleocytosis. The proportion of T cells marking with anti Tac, a measure of T cell activation, in blood and CSF of control animals is 12%, rising to 23% in blood in the post-acute phase of the disease. However, a fall in the blood Tac/T ratio to 13% occurs during the first 10 days of relapse with a subsequent rise to 30-35%. This change is related to the time after onset of relapse irrespective of the subsequent course of the disease. From first relapse onwards CSF lymphocytes show a greater level of activation than lymphocytes from paired peripheral blood samples but the proportion of Tac+ cells in CSF does not increase with increasing CSF pleocytosis. The data is consistent with migration of activated T cells from blood to CSF at the onset of relapse. PMID- 3106415 TI - Calcium ionophore, phorbol ester, and chemotactic peptide-induced cytoskeleton reorganization in human neutrophils. AB - Formyl-methionylleucylphenylalanine (fMLP) activation of neutrophils causes an increase in intracellular Ca2+, activation of protein kinase C and an increase in F-actin content. To examine the role of Ca2+ and protein kinase C activation as determinants of change in F-actin content of neutrophils, we used the NBD phallacidin extraction assay to compare the kinetics and extent of change in F actin content of cells activated with fMLP, the calcium ionophore A23187 or phorbol myristate acetate (PMA). All stimuli increase the F-actin content in a dose-dependent manner; however, the rate of increase is slower and the maximum F actin content is less for calcium ionophore and PMA than for fMLP-activated cells. The A23187-induced increase in F-actin content, but not that of fMLP, depends upon external free [Ca2+]. In A23187-activated cells, F-actin content increases at [Ca2+]free greater than or equal to 5 microM, is maximal at [Ca2+]free greater than or equal to 10 microM and is negligible at physiologic free [Ca2+] (10(-7)-10(-6) M). Combinations of PMA with A23187 or fMLP inhibit the A23187, but not the fMLP, activated actin polymerization. Comparison and combination of these activators shows that neither Ca2+-dependent activation with A23187 nor activation with PMA alone or in combination mimic the fMLP-induced changes in cytoskeleton organization of neutrophils. PMID- 3106417 TI - n-Butyrate inhibition of hyaluronate synthesis in cultured human fibroblasts. AB - The effects of the short-chain aliphatic carboxylic acid, n-butyrate, on glycosaminoglycan (GAG) accumulation were studied in cultured human skin fibroblasts. Normal fibroblast cultures were grown to confluence, shifted to a medium without or with n-butyrate for 24 h, labeled with either [3H]acetate or [3H]glucosamine and analyzed for [3H]GAG and [3H]hyaluronate accumulation. Accumulation was stimulated at low concentrations (0.1-1 mM) by up to 27%. Higher concentrations of n-butyrate (greater than 1 mM) inhibited [3H]GAG by up to 70 90%. This effect was maximal at 10 mM and half-maximal at 3 mM. Propionate had similar effects but was less potent. Parallel studies conducted in colonic fibroblasts revealed that n-butyrate could markedly inhibit [3H]GAG accumulation in that cell type as well. These effects were rapid, occurring within 3 h of treatment, and were reversible. Chondroitin sulfate accumulation was unaffected by the compound. A pulse-chase study failed to demonstrate any effect on [3H]GAG degradation. PMID- 3106418 TI - High-resolution ultrasonography of wrist ganglia. AB - High-resolution ultrasonography was performed on 14 patients with soft tissue swelling of the wrist and hand. The examination was done using a real-time 10-MHz sector probe placed directly on the lesion. The sonographic image could always demonstrate the liquid nature of cystic lesions. In recent ganglia, the fluid content was anechoic, and the cystic walls were rather thin; in some older lesions, irregular internal echoes and thicker walls were found. Rather often, multiple ganglia were observed, grouped in clusters. The presence of a liquid filled duct directed to the articular space was demonstrated in 8/11 cases (73%). This finding is considered a diagnostic characteristic of ganglia, and it is very useful for correct surgical planning. In extensor cystic tenosynovitis, the echographic picture was quite different: the anechoic cavity was longitudinal in shape, following the tendon sheath, and the communicating duct was absent. Finally, the sonographic pattern of one case of de Quervain's disease was analyzed and discussed. PMID- 3106416 TI - Inhibition of human endothelial cell proliferation by gold compounds. AB - Neovascularization has a role in the propagation of rheumatoid synovitis because the spread of mononuclear cell infiltration and the growth of pannus are dependent on the growth of new blood vessels. Growth of such vessels requires local endothelial cell (EC) proliferation. Inhibition of synovial EC proliferation, therefore, would have the potential to diminish rheumatoid inflammation. We have, therefore, studied the effects of gold sodium thiomalate (GST), auranofin, and gold chloride on the proliferation of human umbilical vein EC. GST suppressed both basal and EC growth factor-induced tritiated thymidine incorporation into EC in a dose-dependent fashion. Inhibition was observed with concentrations as low as 1 microgram/ml GST, 5 micrograms/ml gold chloride, and 0.1 microgram/ml auranofin, levels attainable in blood and synovium of patients. These results suggest that gold compounds have an antiangiogenic effect. The low concentrations inhibiting EC proliferation suggest that gold compounds may suppress rheumatoid synovitis by reducing the number of small blood vessels available for mononuclear cell infiltration and synovial tissue proliferation. PMID- 3106419 TI - Mathematical modeling of fetal growth. III. Evaluation of head growth using the head profile area. AB - Growth of the fetal head has been reexamined in a longitudinal study of 32 normally growing fetuses using the head profile area (HA). The Rossavik growth model (characterized by the coefficients c, k, and s) fit these data very well (R2 [+/- SD] 99.6 [+/- 0.3]%), and regression analysis indicated that optimum results are obtained when the coefficient k is kept constant. Head area growth before 28 weeks was found to be related to the coefficient c, which was strongly correlated (R2 69.2%) with the time of HA growth initiation. These results suggest that c reflects the genetic factors controlling growth in the early part of pregnancy. The coefficient s was negatively correlated with c (R2 82.1%) and had two components, one associated with c (pred. s) and one not associated with c (s-residual). This linkage between c and s, together with the parallel head growth seen after 30 weeks, suggests the possibility of a maternal system in which genetically determined head size (c) can be sensed and modified by other factors (s) to maximize compatibility between the fetal head and maternal pelvis. PMID- 3106420 TI - Prenatal diagnosis of bilateral cystic adenomatoid malformation of the lung. AB - Bilateral cystic adenomatoid malformation of the lung (CAML), solid type (Stocker III), is a rare malformation that we observed sonographically in two fetuses at 23 weeks. The ultrasonic image showed an echogenic mass compressing the heart and occupying the whole thoracic cavity. Massive ascites, probably as a result of heart failure, was apparent. The prognosis is fatal. Prenatal diagnosis enables termination of pregnancy and saves the mother from invasive procedures in case of fetal distress. In unilateral, more favorable lesions, the managing physician is prepared for respiratory distress of the newborn and an emergency operation. PMID- 3106421 TI - Mathematical modeling of fetal growth. IV. Evaluation of trunk growth using the abdominal profile area. AB - Growth of the fetal abdomen has been reexamined in a longitudinal study of 32 normally growing fetuses using the abdominal profile area (AA) and the Rossavik growth model. The growth of the fetal abdomen was compared to that of the fetal head. In early pregnancy the growth rate was higher for the fetal head than for the fetal abdomen, whereas the opposite was the case in late pregnancy. The coefficient k was lower, and the s was higher, for AA than for the head profile area (HA), giving a less prominent sigmoid shape to the AA growth curve. The best correlation to fetal weight at birth was found for the AA growth curve as a whole. The AA s-residual correlated best of all single parameters, with the coefficient c of HA being next. The s-residual appears to reflect the nutritional supply available in late pregnancy, and we conclude that fetal weight at birth depends more on this supply than on the genetic factors controlling fetal growth. PMID- 3106422 TI - Ultrasonography of the acute scrotum. AB - The acute scrotum remains a difficult clinical challenge because of numerous etiologies including inflammatory processes, testicular torsions, traumas, and tumors that can justify early surgery. Ultrasound study appears to be the imaging modality of choice to confirm the clinical assessment. We reviewed 825 scrotal scans performed with high-resolution scanners; 283 were considered pathologic and classified as follows: 27 tumors (9.5%), 21 traumas including torsions (7.4%), 142 infectious diseases (50.1%), 99 dystrophic diseases (29.2%), and 16 miscellaneous (5.6%). Acute scrotal pain was the only symptom in 83 cases (29.3%). In this paper, we emphasize the different roles of ultrasound depending on the initial clinical presentation, which determines the clinician's questions. In the typical cases, ultrasound has a major role in the prognosis, as it allows evaluation of the severity of the lesions. On the other hand, in atypical cases, ultrasound has a decisive role in planning the management, which will be immediate surgery when sonographic findings highly suspicious for testicular torsion or acute ischemia of the testis are found. Based on our experience, we believe that ultrasound is a highly reliable modality for guiding medical or surgical treatment of an acute scrotum. PMID- 3106423 TI - Ultrasonic presentation of giant hydrosalpinges in asymptomatic patients. PMID- 3106424 TI - Ultrasonography of acute obstructive suppurative cholangitis: serial observation by ultrasound. PMID- 3106425 TI - Hepatic scar along a transhepatic biliary drainage tract simulating metastatic diseases. PMID- 3106426 TI - Prenatal ultrasound diagnosis of thoracopagus conjoined twins. PMID- 3106427 TI - Combined contrast echocardiographic and hemodynamic evaluation of atrial septal defect associated with persistent left superior vena cava and partial anomalous pulmonary venous connection. PMID- 3106428 TI - Sonographic changes in a parasagittal cerebral lesion in an asphyxiated newborn. PMID- 3106429 TI - A new ultrasound annotation and report card system. PMID- 3106430 TI - Clinical experience with intraoperative Doppler color flow imaging in hepatectomy. AB - Real-time two-dimensional Doppler echography (2-D Doppler), which permits both structural and blood flow evaluations simultaneously, was applied during hepatectomy in three cases. Intrahepatic portal flow was observed in one case both before and after Pringle's maneuver. Hemihepatic blood flow interruption, which was guided by 2-D Doppler imaging, was tried in two cases. Extrahepatic blood flow was also detected easily with 2-D Doppler techniques. This approach is useful for both anatomic and hemodynamic evaluation during hepatic surgery. PMID- 3106431 TI - Distribution of carbonic anhydrase activity in neurons of the rat. AB - Certain neurons of dorsal root ganglia (DRG) and some fibers of the sciatic nerve contain histochemically demonstrable carbonic anhydrase activity. Since the distribution of this enzyme throughout the nervous system has not yet been evaluated systematically, we conducted a comprehensive histochemical survey focusing particularly on structures derived from the neural crest and nonneural crest ectoderm. In the peripheral nervous system, we observed carbonic anhydrase activity in some, but not all, neurons of dorsal root, trigeminal, celiac, and myenteric ganglia as well as in glial cells throughout the CNS. Some neurons of the nodose ganglion also showed carbonic anhydrase activity. In all first order sensory ganglia that were studied, the enzyme was found only in large (50 micron or above) and medium (20-50 micron) size neurons; in the case of spinal ganglia, the reactive neurons constituted approximately 30% of the total neuronal population. Of these reactive neurons, 56% were heavily stained and 44% were moderately stained. Several possible roles for neuronal carbonic anhydrase are considered. PMID- 3106432 TI - Resting metabolic rates in boid snakes: allometric relationships and temperature effects. AB - Resting metabolic rates (RMR) of 34 species from 18 genera of boas and pythons (Serpentes: Boidae), with body masses ranging from 2 to 67,800 g, were determined as oxygen consumption (VO2) and carbon dioxide production (VCO2) at three ambient temperatures (Ta). The temperature coefficient of metabolism (Q10) averaged 2.61 between Ta of 20-30 degrees C and 2.65 between 30 and 34 degrees C. The respiratory exchange ratio RE (= VCO2/VO2) increased slightly with increasing Ta (0.795 at 20 degrees C, 0.819 at 30 degrees C, and 0.834 at 34 degrees C). Interspecific differences in Q10 and RE were slight or insignificant. A multiple regression relating metabolism (VO2) to mass and Ta explained 97% of the variance in the pooled interspecific data. The mass exponent was 0.806, which is approximately the same as reported for squamates and for all reptilian taxa combined. The mean within-species slope (0.732) was significantly less than the slope for pooled data, but did not differ significantly from 0.75. In 40 of 42 cases (14 species at 3 Ta), within-species slopes did not differ from each other. Values of the adjusted mean Y, from covariance analysis, were significantly and positively correlated with mass, indicating that the mass coefficient increases with increasing mass. Considerable variation in metabolic rate is apparent both within and between ecological and taxonomic categories. PMID- 3106433 TI - Simplified, noninvasive PET measurement of blood-brain barrier permeability. AB - Blood-brain barrier (BBB) permeability to [68Ga]EDTA was measured by positron emission tomography (PET) in four normal volunteers and in 11 patients with brain tumors. A unidirectional transfer constant, Ki, was calculated applying multiple time graphical analysis (MTGA). This method allows the detection of backflux from brain to blood and, by generalization, the measurement of the constant Kb (brain to blood). Furthermore, the need for an independent measurement of the intravascular tracer is obviated: MTGA itself provides an estimate of the cerebral plasma volume (Vp). In the four normal volunteers the Ki was 3.0 +/- 0.8 X 10(-4) ml g-1 min-1 (mean +/- SD) and the Vp 0.034 +/- 0.007 ml g-1. A net increase in Ki up to a maximum of 121.0 X 10(-4) ml g-1 min-1 (correspondent value of Kb = 0.025 min-1) as well as an increase of Vp was observed in malignant tumors. The input function was calculated using both the [68Ga]EDTA concentration in sequential arterial blood samples and, noninvasively, the activity derived from the superior sagittal sinus image. The values of Ki and Vp from these two calculations were in good agreement. The application of MTGA to PET permits the evaluation of passage of substances across the BBB without making assumptions about the compartments in which the tracer distributes. PMID- 3106434 TI - The Historical Museum of Medicine and Dentistry and how do we individually relate to it? What is our role in its future? PMID- 3106435 TI - Drugs, your patient, and you: the need for a continually updated medical history. PMID- 3106436 TI - Controlled substances prescribing guide for Connecticut dentists compiled by the Connecticut Joint-Dental Pharmaceutical Committee with the assistance of the Drug Control Division of the Connecticut Department of Consumer Protection. PMID- 3106437 TI - Infection in the compromised host (the fatal periodontal pocket). PMID- 3106438 TI - Recent advances in antimicrobial therapy. PMID- 3106439 TI - Osteomyelitis of the maxilla. Report of a case. PMID- 3106441 TI - The state of economic health of dentists in the U.S.A. with a special focus on New England. PMID- 3106440 TI - Assessment of wide tips for visible light curing units. PMID- 3106442 TI - Survival of lactic acid bacteria in the human stomach and adhesion to intestinal cells. AB - The survival of four strains of lactic acid bacteria in human gastric juice, in vivo and in vitro, and in buffered saline, pH 1 to 5, has been investigated. The strains studied include two Lactobacillus acidophilus strains, Lactobacillus bulgaricus, and Streptococcus thermophilus. In addition, the adhesion of these strains to freshly collected human and pig small intestinal cells and to pig large intestinal cells has been studied and the effect of milk on both survival and adhesion tested. As a result of these investigations, an in vitro test system for screening potential cultures for use as human dietary adjuncts can be developed. The ability to survive in gastric juice and to adhere varied significantly for the strains tested; L. acidophilus ADH survived and adhered better than the others while S. thermophilus survived and adhered poorly. For all strains, both survival and adhesion was enhanced by milk. As all strains adhered to some extent to both human and pig intestinal cells, the adhesion mechanism is probably a nonspecific attachment as opposed to other reported specific Lactobacillus adhesion to gastric tissue. From the survival and adhesion data it seems feasible to obtain elevated levels of viable Lactobacillus sp. in human intestine by careful selection of the bacterial strains ingested. Furthermore, the in vitro methods used here should be valuable to screen potential strains. The data presented here can then be correlated with human in vivo studies monitoring the beneficial effect of ingestion of these Lactobacillus. PMID- 3106443 TI - Phage resistance in Streptococcus lactis ssp. diacetylactis transconjugant SLA3.2501 and its derivatives. AB - Phage 18-16, which was virulent for Streptococcus lactis ssp. diacetylactis SLA3.25 was used to study phage-resistant characteristics of mucoid S. lactis ssp. diacetylactis transconjugant SLA3.2501 obtained through conjugative cotransfer of pSRQ2201 (Lac-plasmid) and pSRQ2202 (Muc-plasmid) to SLA3.25 (15). Interaction of phage 18-16 with SLA3.2501 and its derivatives showed that phage resistance was not related to either the lack of phage adsorption or restriction modification. Suppression of phage replication in SLA3.2501 and its derivatives was not completely relieved by curing of either pSRQ2201 or pSRQ2202 or both. PMID- 3106444 TI - Growth hormone-releasing factor effects on pituitary function, growth, and lactation. AB - Growth and lactation are complex processes controlled by several metabolic hormones such as insulin, glucagon, and thyroid hormones but most notably growth hormone. Growth hormone secretion is regulated by two hypothalamic hormones, somatostatin, an inhibitory regulatory factor, and growth hormone-releasing factor. The quantity and pattern of growth hormone secretion is ultimately regulated in concert by the secretion of both regulatory factors from the hypothalamus through the hypothalamo-hypophyseal portal system, where they exert their actions at unique pituitary receptors. Because the potential use of exogenous growth hormone administration for the stimulation of growth efficiency and lactation has been demonstrated, recent efforts have been directed toward the enhancement of production through manipulation of endogenous growth hormone secretion via its releasing factor. Thus far, releasing factor-stimulated growth and lactation has not been achieved to the same extent as that of exogenous growth hormone. Growth hormone-releasing factor has stimulated growth in two growth hormone-deficient children, as well as female, but not male, rats. Although all food-producing species tested to date respond to growth hormone releasing factor with the appropriate growth hormone response, continuous or pulsatile administration of releasing factor has not resulted in increased growth rate in sheep, chicks, or hogs. Despite levels of circulating growth hormone that would be expected to produce a 30% increase in milk production if given exogenously to dairy cows, releasing factor-stimulated growth hormone secretion has resulted in only a 3 to 9% increase. It is clear from these studies that further developments are necessary to demonstrate the practical application of growth hormone-releasing factor. PMID- 3106445 TI - Long-term effects of family-based treatment of childhood obesity. PMID- 3106446 TI - APACHE II. PMID- 3106447 TI - Alpha-myosin heavy chain isoform and atrial size in patients with various types of mitral valve dysfunction: a quantitative study. AB - The cardiac myosin phenotype, an important determinant of myocardial contractility, is modified by chronic increases in hemodynamic load. To quantify the proportion of atrial alpha-myosin heavy chain in various types of left atrial overload and to assess the possible relation between this proportion and atrial size, 34 patients were studied, 4 with Wolff-Parkinson-White syndrome, 29 with various types of mitral valve dysfunction and 1 with an atrial septal defect. Four normal autopsy hearts were also studied. The proportion of alpha-myosin heavy chain among total (alpha plus beta) myosin heavy chains was determined in each atrial sample, using an enzyme-linked immunosorbent assay. The size of the left atrium was assessed by one- and two-dimensional echocardiography. Alpha myosin heavy chain was the main isoform present in the normal atria (85.5 +/- 9% of total myosin heavy chains). Patients with pure tight mitral stenosis (n = 9), mitral stenosis plus mild regurgitation (n = 8) and severe mitral regurgitation (n = 8), who had a higher indexed left atrial transverse diameter than those with Wolff-Parkinson-White syndrome (33 +/- 6, 39 +/- 10 and 46 +/- 5 versus 19.5 +/- 2 mm/m2, p less than 0.01, p less than 0.001 and p less than 0.001, respectively), also demonstrated a much smaller percent of alpha-myosin heavy chain content (28 +/- 20, 23.5 +/- 13 and 12 +/- 10 versus 58 +/- 18%, p less than 0.01, p less than 0.01 and p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106448 TI - Chrysotherapy in the treatment of corticosteroid-dependent asthma. AB - The efficacy of parenteral gold therapy was evaluated in patients with steroid dependent asthma. Five of eight patients improved in terms of reduced steroid requirement while they were maintaining or improving lung function. Two patients developed significant proteinuria that resolved with cessation of gold. Chrysotherapy appears to have a corticosteroid-sparing effect in some patients and may have a useful role in the management of severe refractory asthma. PMID- 3106449 TI - Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. AB - Single-dose salbutamol (200 micrograms), beclomethasone dipropionate (200 micrograms), and sodium cromoglycate (SCG) (10 mg) administered by inhalation 10 minutes before allergen challenge were examined with regard to inhibition of allergen-induced early (EAR) and late (LAR) asthmatic responses and allergen induced increase in bronchial responsiveness to inhaled histamine. Ten atopic subjects with asthma participated in a blinded, crossover, placebo-controlled trial. The EAR was inhibited by salbutamol and SCG but not by beclomethasone dipropionate or placebo (p less than 0.01). The LAR (p less than 0.01) and the allergen-induced increased bronchial responsiveness to histamine 7 hours (p less than 0.01) and 30 hours (p less than 0.05 and p less than 0.01 for various comparisons) were inhibited by SCG and beclomethasone diproprionate but not by salbutamol or placebo. The allergen-induced LAR and associated increased responsiveness are now believed to be more important clinically than the EAR. The clinical relevance of these results is to stress the importance of the prophylactic nonbronchodilator drugs (SCG and steroids) and the potential inadequacy of bronchodilators used alone in the treatment of both perennial and seasonal allergic asthma. PMID- 3106450 TI - Effects of two doses of cromolyn on allergen-induced late asthmatic response and increased responsiveness. AB - We selected five atopic children with asthma with previously documented late asthmatic response (LAR) associated with increased hyperresponsiveness to methacholine after the inhalation of Dermatophagoides pteronyssinus. The children had four allergen inhalation tests on 4 different days, at least 14 days apart. On days 1 and 4, saline placebo was inhaled 1 hour before the expected onset of LAR, and FEV1 was measured hourly until FEV1 returned within 10% of baseline value; then methacholine challenge was performed. On days 2 and 3, 20 and 40 mg of cromolyn was inhaled double blind 1 hour before the expected onset of LAR. FEV1 and methacholine responsiveness were measured as on days 1 and 4. The two doses of cromolyn significantly delayed the LAR onset without altering the overall LAR magnitude and prevented the allergen-induced increase in methacholine responsiveness. Both these effects were greater at the maximal dose used. We conclude that cromolyn can prevent the allergen-induced increase in methacholine responsiveness and that this effect is not due to alteration in the magnitude of LAR. Our findings reveal a possible explanation of the effectiveness of this drug in the treatment of allergic asthma. PMID- 3106451 TI - A computerized diet analysis system for the research nutritionist. AB - A computerized diet analysis system can assist in the many dietary computations performed daily by the research nutritionist. When selecting a computerized diet analysis system, the research nutritionist must consider present and future needs and select a system that is accurate, efficient, and cost-effective. The purpose of this article is to review the computer needs of the research nutritionist, identify areas to be considered when selecting a diet analysis system, and describe a system that functions easily in research or clinical settings. The diet analysis system described here is interactive and easy to use and provides flexible programming to accommodate changing research or clinical needs. The nutrient data base is accurate, verified, and periodically updated by the company that provides the system. Data entry is easy, and new foods or recipes can readily be added to the nutrient data base. The system's programs and special features provide efficient, accurate methods for creating and analyzing complex research diets, analyzing nutrient intake, and reporting nutrient data. PMID- 3106452 TI - Geriatric patient outcomes and costs in three settings: nursing home, foster family, and own home. AB - Forty-nine matched triads of geriatric patients were compared after three months in their respective placement settings: nursing homes, geriatric foster homes, and own homes with supportive services. Compared to similarly disabled patients in nursing homes, patients in the two community settings made greater improvements in self-care skills and mobility, expressed greater well-being, had similar types and amounts of morbidity, and entailed lower costs. The results support the expansion of home and community-based services as alternatives to institutional care for a substantial number of geriatric patients. PMID- 3106453 TI - UCLA geriatric grand rounds: diabetes in the elderly. PMID- 3106454 TI - AIDS and the geriatrician. AB - Ten percent of acquired immune deficiency syndrome (AIDS) cases are in persons over 50 years of age with 25% of these cases in persons over 60, and 4% in persons over 70 years of age. If the present age distribution holds, there will be 27,000 AIDS cases in persons over 50, and 1100 cases in persons over 70 years of age, by 1991. Older persons are more likely to acquire AIDS through blood transfusions than to homosexual exposure or drug abuse. Changes in the management of blood products will benefit older persons. The nearly 1 million elderly homosexual men, who have been sheltered from the virus by their pattern of sexual activity, will face greater risks as the prevalence of the virus and the age of the carriers increases. The underappreciated neurological consequences of human T cell lymphotrophic virus type III (HTLV-III) infection, subacute encephalitis, vacuolar myelopathy, and psychiatric disorders will be of particular interest to geriatricians who are often consulted to evaluate neurological dysfunction. Geriatricians will need to become familiar with the spectrum of HTLV-III infection and prepared to counsel patients and extended-care facilities. PMID- 3106455 TI - Effects of 6-hydroxydopamine and the PNMT inhibitor LY134046 on pressor responses to stimulation of the subretrofacial nucleus in anaesthetized stroke-prone spontaneously hypertensive rats. AB - The subretrofacial nucleus of the rostral ventrolateral medulla is an important site for the control of sympathetic vasomotor tone and is the location of the C1 PNMT-containing cell bodies. In the present study the involvement of central monoaminergic neurons in the pressor responses evoked by chemical or electrical stimulation of this nucleus was examined in urethane-anaesthetized stroke-prone spontaneously hypertensive rats (SHRSP). Vehicle-treated rats were compared to animals treated with the PNMT inhibitor LY134046, the catecholamine neurotoxin 6 hydroxydopamine (6-OHDA) or a combination of 6-OHDA and the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). LY134046 caused a 43% depletion of adrenaline content in the hypothalamus and medulla but not in the spinal cord but had no effect on the pressor responses to stimulation of the subretrofacial nucleus. However, intraventricular administration of 6-OHDA reduced the pressor responses to subretrofacial nucleus stimulation by 50%. 6-OHDA caused profound depletion of noradrenaline in the brain and spinal cord, and adrenaline in the hypothalamus. Combined treatment with 6-OHDA and 5,7-DHT caused the additional depletion of serotonin to 34% and 13% in the hypothalamus and spinal cord, respectively, but caused no further reduction of pressor responses than with 6-OHDA alone. These results suggest that the pressor responses elicited by subretrofacial nucleus stimulation involve a 6-OHDA-sensitive pathway (presumably catecholaminergic) other than the bulbospinal adrenaline pathway but that serotonergic mechanisms do not contribute. PMID- 3106456 TI - The visualisation of cardiovascular innervation in the guinea pig using an antiserum to protein gene product 9.5 (PGP 9.5). AB - The various subpopulations of autonomic and sensory nerves supplying the mammalian cardiovascular system may be demonstrated using specific immunocytochemical and histochemical techniques, but no single marker has previously been available for the visualisation of the entire innervation. Protein gene product (PGP) 9.5 was first identified in extracts of human brain and found to represent a major protein component of the neuronal cytoplasm. We have demonstrated that PGP 9.5 immunoreactivity occurs in the guinea pig cardiovascular innervation and is present in more individual nerve fibres than other general neuronal markers (neuron-specific enolase and neurofilaments). PGP 9.5 immunoreactivity was localized to both intrinsic neurones and nerve fibres in the guinea pig heart. In the vascular system PGP 9.5-immunoreactivity occurred in an extensive plexus of fine perivascular nerve fibres and fascicles running around and along both arteries and veins, mainly at the adventitial-medial border. At the ultrastructural level, this immunoreactive material was localized to the axonal cytoplasm and did not appear to be associated with cytoskeletal elements or secretory vesicles. 6-Hydroxydopamine (6-OHDA) pretreatment resulted in the degeneration of noradrenergic axon terminals containing PGP 9.5, tyrosine hydroxylase (TH) and neuropeptide tyrosine (NPY) immunoreactivities. Most of the perivascular nerve fibres which remained displayed substance P- and calcitonin gene-related peptide (CGRP) immunoreactivity, as well as PGP 9.5 immunoreactivity. Capsaicin pretreatment resulted in a depletion of both substance P and CGRP immunoreactivity, but had no apparent effect on PGP 9.5 immunostaining. In the heart PGP 9.5 immunoreactivity also appeared to be present in presumed postganglionic cholinergic nerves. PGP 9.5 may be a useful marker when examining regional variations in cardiovascular innervation and for determining the relative proportions of nerve subpopulations. PMID- 3106457 TI - [Macular manifestations of monoclonal dysgammaglobulinemias. Apropos of 3 cases]. AB - Macular oedema is one of the scarcely known manifestations of monoclonal dysglobulinemia. It is most common in Waldenstrom's macroglobulinemia because the serum's viscosity may reach a very high level, but it occurs also in multiple myeloma (first case described here). This specific oedema is secondary to immunoglobulin deposits in retinal layers and subretinal space. Early treatment is necessary to prevent irreversible visual loss, especially because the patient's expected life span becomes lengthened. Plasmaphereses are very useful in reducing serum's hyperviscosity, and rapidly improve most of the ocular manifestations. PMID- 3106458 TI - Growth hormone and somatomedin-C response to synthetic human pancreatic tumor GH releasing factor in hypopituitary and constitutionally short children. AB - GH and somatomedin-C response to acute hpGRF-44 iv administration (1 microgram/Kg bw) was studied in 16 patients with hypopituitarism (GHD) and in 7 constitutionally short subjects. GH-deficient patients evidenced a significant GH increase peaking between 15 and 60 min. (4.95 +/- 0.88 ng/ml, mean +/- SE) (p less than 0.01 vs placebo). In non GH-deficient subjects GH increase was more pronounced (peak 18.00 +/- 3.01 ng/ml; p less than 0.01 vs both placebo and GHD group). Acid-extractable somatomedin-C was slightly, but significantly higher than baseline at 12th h (p less than 0.01) in both patients with hypopituitarism (basal value: 0.067 +/- 0.021 U/ml; 12 h: 0.096 +/- 0.024 U/ml) and constitutionally short subjects (basal value 0.62 +/- 0.13; 12h 0.72 +/- 0.16 U/ml). In 3 subjects with hypopituitarism multiple iv administrations (1 microgram/kg bw at 09:30 and 21:30 h for 4 days) produced on the average a modest increase of the GH responsiveness, were more effective to enhance somatomedin-C concentration, but not sufficient to reach normal levels. Sc administration of the same dose at 4-h intervals by a programmable portable pump - performed on 6 GHD subjects - produced an increase of GH peak response on the 4th day of treatment (1.38 +/- 0.31 ng/ml) with respect to the one observed on the first day (0.42 +/- 0.09 ng/ml). Somatomedin-C increase was low and inconstant. These data support the use of a 4-5-day pulsatile treatment in the differentiation between hypothalamic and pituitary deficiency, and the possibility of therapeutical use of GRF with the same protocol when a response is evidenced. PMID- 3106460 TI - Synthetic growth hormone-releasing hormone (GHRH 1-44) in the differential diagnosis between hypothalamic and pituitary GH deficiency. AB - GH response to an iv bolus of growth-hormone-releasing hormone (GHRH 1-44, 2 micrograms/kg iv) was evaluated in 17 prepubertal children with total GH deficiency (GHD), 6 with partial GHD and in 7 prepubertal normal but short children tested as control. GH response to conventional pharmacological (insulin and arginine or L-Dopa) and physiological stimuli (sleep test) and to GHRH test was also compared. GHRH-induced GH peak occurred at variable times and marked heterogeneity in magnitude of the individual responses to this peptide was observed in GHD patients and in controls. GH increases after GHRH with a peak greater than 10 ng/ml suggested an hypothalamic origin of the GHD in 12 patients (8 with total GHD and 4 with partial GHD). A significant difference (p less than 0.025) of GH peak mean following GHRH administration between total GHD children and normal short children was found. GH response to GHRH injection was usually higher than to conventional stimuli. Nevertheless GH peak following GHRH administration was lower than GH peak following conventional stimuli in 6 children (2 partial GHD children and 4 normal ones). A normal short child failed to respond to GHRH test performed twice. GHRH test is an important diagnostic tool in order to point out hypothalamic GHD. PMID- 3106461 TI - Finding the levers, finding the courage: lessons from cost containment in North America. AB - "Learning" is broader and more complex than simply the orderly acquisition of new knowledge. At least as important is the evolution of the background of assumptions and beliefs held by the community, or its principal decision makers, and implicit in its institutions and policies. These may bear only a loose relation to evidence or knowledge narrowly defined. The pressures of cost escalation over the past twenty years, and the attempts at containment in the U.S. and Canada, have added substantially to our knowledge of how the health care system works. Containment is possible, and the successful mechanisms, thus far, are quite specific. But the results of these attempts and (in the U.S.) the continued escalation have also significantly shifted the broader set of assumptions in the community about appropriate priorities and policies in health care. Attitudes towards physician supply, variations in practice patterns, capitated practice, and for-profit organization, for example, have changed radically, although the supporting evidence has not. But cost pressures have created an audience which wants to hear, whose background assumptions provide a different "fit" for the evidence. PMID- 3106459 TI - Effect of simultaneous administration of GHRH (1-40) and TRH on GH, PRL and TSH secretion in normal man. AB - The GHRH test represents a new tool in the study of secretion in man. Nine normal fasting males received on separate occasions in random order 1) GHRH 1-40 (1 microgram/Kg bw) iv at time 0; 2) TRH (6 micrograms/min) infusion between -30 and +120 min; 3) GHRH 1-40 (1 microgram/Kg bw) iv at time 0 plus TRH (6 micrograms/min) infusion between -30 and +120 min. Blood samples were drawn for GH, PRL and TSH at -90, -60, -30, 0 min and then every 15 min for 2 h. GHRH significantly increased GH in all subjects. The same GH response was found during GHRH plus TRH test. No effect was found either on PRL and TSH secretion after GHRH administration, or on GH pattern after TRH administration. A significant decrease of TSH, but not of PRL response was observed after GHRH plus TRH administration in comparison to TRH alone. These results underline that the inhibitory effect exerted by TRH on GH secretion during some experimental conditions is not linked to a pituitary interference between GHRH and TRH. The difference in TSH secretion, following GHRH plus TRH in comparison with TRH alone, could be due to a GHRH-induced central inhibitory mechanism, probably GHRH related. PMID- 3106462 TI - New federalism and health care policy: states and the old questions. AB - The New Federalism that evolved under the Reagan administration tends to grant states more discretion in the implementation of health care programs. It thereby rekindles old concerns about the commitment, capacity, and progressivity of the states. This paper reviews recent policy developments and reconsiders state performance from the vantage point of the mid-1980s. While hard evidence remains elusive, a plausible case exists that any gap between the states and Washington on commitment, capacity, and progressivity has diminished. State administrative capacity in particular has probably increased. The continued presence of substantial variation among the states needs to be underscored, however. Moreover, the relentless imperative of economic development, or migration, theory sets severe limits on how far states can go in adopting redistributive measures to assure adequate medical care for the poor. Given current federal laws, the most optimistic, plausible scenario envisions the rise of a technical politics of efficiency in the states. In spite of state limitations, health policy reformers need to pay increased attention to their potential role. PMID- 3106463 TI - Severe intrahepatic cholestasis and rapidly progressive renal failure in a patient with immunocyte-related amyloidosis. AB - A woman developed severe cholestatic jaundice and progressive renal failure secondary to amyloid deposition. The amyloid protein was of AL type, consisting of IgG-related kappa chains. This form of amyloidosis is classified as immunocyte related, not associated with myeloma. PMID- 3106464 TI - Issues in the application of high cost medical technology: the case of organ transplantation. PMID- 3106465 TI - Inhibition of Plasmodium knowlesi isoenzyme bands using antibody produced by lymphocyte hybridoma technique. PMID- 3106467 TI - Carbonic anhydrase III: a new histochemical marker for myoepithelial cells. AB - Carbonic anhydrase III, a major protein of red skeletal muscle, was localized immunohistochemically in smooth muscle cells of human uterus and in myoepithelial cells of mammary and prostate glands. The presence of this antigen in myoepithelial cells could be used to detect these not easily recognizable cells in paraffin-embedded tissue sections. Some epithelial cells of larger mammary ducts revealed occasional strongly positive cells. These cells may represent a new epithelial cell type transitional between myoepithelium and ductal epithelium. PMID- 3106466 TI - The involvement of eggs and soluble egg antigens in resistance to Schistosoma japonicum. AB - Mice presensitized with SEA and subsequently injected with S. japonicum eggs into their lungs or liver developed pathology similar to that found in infected mice and were consequently resistant to challenge (average 33% and 53%, respectively). However, soluble egg antigens were also capable of inducing low levels of resistance in mice (average 22.5%), but intact eggs alone injected into the lungs, liver or subcutaneous tissues were not. Thus, prior sensitization to 'marginally' protective soluble egg antigens is necessary for egg induced resistance. PMID- 3106468 TI - Leu-7 immunoreactivity in human, monkey, and pig bronchopulmonary neuroepithelial bodies and neuroendocrine cells. AB - Anti-Leu 7 is a monoclonal antibody recognizing a surface antigen on human natural killer cells. By applying the indirect immunoperoxidase method, we demonstrated Leu-7 immunoreactivity in the cytoplasm of neuroepithelial bodies (NEB) and neuroendocrine cells (NEC) of human, monkey, and pig respiratory mucosa. In addition, the anti-Leu-7 monoclonal antibody stained the myelin sheaths of nerve fibers in all tissues investigated. Our findings support the hypothesis that shared antigens exist between the nervous, endocrine, and immune systems. PMID- 3106469 TI - Unusual binding sites for horseradish peroxidase may contribute to "background" adsorption of the enzyme. PMID- 3106470 TI - Effect of oxytetracycline and erythromycin on Syrian hamsters after intratracheal infection with Mycoplasma pneumoniae. AB - Male Syrian hamsters were infected intratracheally with Mycoplasma pneumoniae and treated here after for ten days with either OTC or erythromycin. The purpose of this study was to investigate whether there exists a relation between the persistence of M. pneumoniae in the lungs and the infection dose respectively the days passed after infection before starting treatment with antibiotics. The influence of antibiotic therapy on the immune response of the hamsters was also investigated. PMID- 3106471 TI - Heterogeneity of signal requirements in T cell activation within a panel of human proliferative T cell clones. AB - Activation of T lymphocytes is initiated by receptor ligand interactions at the cell surface leading to the transduction of intracellular signals followed by the de novo synthesis and expression of T cell activation markers (including receptors for interleukin 2 (IL 2) and transferrin), production of lymphokines, and T cell proliferation. This requisite first step for activation of T lymphocytes can be mimicked in certain situations with a variety of stimuli. These include antibodies to certain integral membrane proteins, phorbol esters, and plant lectins that act as mitogens. In this paper, we report that at least two classes of human T cell clones can be distinguished based upon signal requirements necessary to induce proliferation. Although all clones analyzed expressed IL 2 receptors and secreted IL 2 after non-antigenic activation, one subset of clones did not proliferate in response to the same non-antigenic signals. In that subset, complete activation leading to proliferation required interaction of the T cell with specific antigen. The ability to subset these T cell clones into two groups did not correlate with phenotypic differences, source of the clone, nor with magnitude of intracellular calcium mobilization. By studying the stimulation requirements of these two subsets of human T cell clones through the use of specific antigen or antigen-independent stimuli, it was possible to demonstrate that different stimuli varied in their ability to induce steps of T cell activation. Analysis of reactivity of these clones to suboptimal stimulation allowed the definition of intermediate stages of T cell activation. Such intermediate stages might reflect a diversity of intracellular signaling pathways or a complexity of regulatory mechanisms distal to the events that allow intracellular calcium mobilization. Thus for the first time, it has been possible to study ordered events of T cell activation in non-transformed, antigen dependent human T lymphocytes. The data presented in this paper suggest that T cell activation is not an all or nothing phenomenon, and there is an ordered sequence of events that can be differentiated based upon signal requirements at the T cell membrane. PMID- 3106472 TI - Prostaglandin synthesis in human T cells: its partial inhibition by lectins and anti-CD3 antibodies as a possible step in T cell activation. AB - The human leukemic T cell line Jurkat was used to study arachidonic acid (AA) metabolism. We demonstrated that Jurkat cells are able to convert AA into prostaglandins (PG) and thromboxanes. The presence of tritiated 6-keto-PGF1 alpha, PGE2, PGA2 (B2), and thromboxane B2 in the culture medium was shown either by thin-layer chromatography after a 4-hr incubation period of [3H]AA-prelabeled Jurkat cells or by using specific radioimmuno assays. PG synthesis was inhibited by both indomethacin and niflumic acid, two cyclooxygenase inhibitors. AA metabolism through the cyclooxygenase pathway was followed during T cell activation. T cells were activated by lectins or anti-CD3 monoclonal antibodies (mAb) to trigger the T3-Ti complex and by 12-0-tetradecanoylphorbol 13-acetate (TPA) to mimic IL 1-dependent pathways. Our results show that lectins and anti CD3 mAb both reduce the amount of PG released by the cells, whereas TPA did not. We confirmed that a combination of TPA and lectins or TPA and anti-CD3 mAb is necessary to obtain full activation of Jurkat cells if this event is monitored by using measurement of IL 2 synthesis. In addition, lectins and anti-CD3 mAb can be replaced by the cyclooxygenase inhibitors indomethacin or niflumic acid. Indeed, a combination of TPA and one of these two drugs induced maximal IL 2 synthesis. These results thus suggest that a reduction in PG synthesis might be a prerequisite to allow the cascade of events involved in T cell activation. PMID- 3106474 TI - Distinction of virgin and memory T lymphocytes. Stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic stimulation. AB - The Pgp-1 glycoprotein was identified on a minor (27%) subset of peripheral Lyt 2+ or L3T4+ T cells. In contrast, mature medullary-type thymocytes (Lyt-2+ L3T4-, Lyt-2- L3T4+) were nearly devoid of cells expressing detectable surface Pgp-1. The appearance of peripheral Pgp-1- T cells was found to be thymus dependent, as demonstrated by the diminished proportion of Pgp-1- T cells after thymectomy and their virtual absence in athymic nude mice. The subsequent acquisition of surface Pgp-1 was found to be a stable differentiation event occurring concomitantly with primary antigenic stimulation; selected Pgp-1- mature T cells from thymus or periphery acquired constitutive expression of Pgp-1 after stimulation in vitro with alloantigen or mitogens. These observations were extended by studies in vivo showing that immunization with various antigens augmented the percentage of Pgp 1+ spleen cells within the Lyt-2+ subset. Furthermore, the frequencies of antigen specific CTLp, after immunization by any of three different antigens tested, were greatly enriched in the Pgp-1+ compared with the Pgp-1- subpopulations. Peritoneal exudate Lyt-2+ cells, after a localized allograft rejection, demonstrated a particularly prominent Pgp-1+ subpopulation (78%) that contained virtually all the allospecific cytolytic activity. A model consistent with all of these data proposes that mature thymocytes lacking surface Pgp-1 upon emigration to the periphery acquire its expression at the time of primary antigenic stimulation. Hence, expression of Pgp-1 among peripheral T cells is an important differentiation marker for identifying antigen-stimulated memory T cells. PMID- 3106473 TI - Human T lymphocyte activation by tumor promoters: role of protein kinase C. AB - Protein kinase C (PKC) has a major role in a ligand-receptor-mediated signal transduction system in a variety of cell types including T lymphocytes. One of the early phenotypic changes associated with T cell activation is the expression of cell surface receptors for interleukin 2 (IL 2). To test the role of PKC in regulation of IL 2 receptor (IL 2-R) expression and T cell activation in general, we used tumor promoters (TP) as modulators of PKC and compared their effects on intact human T cells and on the enzymatic activity of T cell-derived PKC in a cellfree system. In T cells, the phorbol ester 12-O-tetradecanoyl phorbol 13 acetate (TPA) induced IL 2-R expression and proliferation associated with cytosol to-membrane PKC translocation. A dose of TPA (1 to 4 ng/ml) that induced about 50% of the maximal activation of PKC in the enzymatic assay also induced half maximal effects on cell proliferation, IL 2-R expression, and PKC redistribution in intact T cells. Structure-function studies with several phorbol ester analogs and non-phorbol ester TP directly correlated tumor promotion activity with the ability to activate PKC and induce IL 2-R. An inhibitor of PKC, chlorpromazine, was found to suppress TPA-mediated proliferation and IL 2-R expression, and inhibited T cell-derived PKC by competing with the phospholipid. Ca2+ ionophore, which synergizes with TPA in induction of T cell proliferation, facilitated the TPA-induced PKC translocation to the membrane. The results thus demonstrate a direct correlation between the effects of various chemicals on: subcellular redistribution of PKC in T cells; induction of T cell proliferation and IL 2-R expression; and activation of T cell-derived PKC in vitro. These data provide further support for the role of PKC in transduction of activation signals in T cells and in regulation of IL 2-R expression. PMID- 3106475 TI - Membrane glycoprotein p150,95 of human cytotoxic T cell clone is involved in conjugate formation with target cells. AB - The p150,95 heterodimer, one of three members of the leukocyte function associated antigen (LFA) family, is expressed by monocytes, granulocytes, NK cells, and a small percentage of lymphocytes. We now report that the p150,95 glycoprotein is expressed by some cytotoxic T cell clones and that it is involved in cell-mediated cytolysis by these clones. Two CTL clones, clone JS-93 (CD3+ CD4+ CD8-) and clone JS-102 (CD3+ CD4- CD8+) expressed high levels of p150,95 and were shown to be specifically directed against HLA-DR and HLA-A2, respectively. Immunoprecipitations followed by two-dimensional gel electrophoresis demonstrated no heterogeneity in the p150,95 molecule isolated from both clones. Furthermore, we demonstrated that monoclonal antibodies (moab) directed against p150,95 could inhibit the cytotoxic activity of both clone JS-93 and clone JS-102 (50% and 47%, respectively). Single cell assays revealed the inhibition to occur at the level of conjugate formation rather than at the level of the lethal hit. Similar results were obtained with moab directed against LFA-1 (p170,95). The capacity of the moab directed against LFA-1 and p150,95 to inhibit CTL activity and conjugate formation were additive, resulting in a similar percentage of inhibition as found with moab directed against the common beta-chain of these molecules. It is concluded that at least some CTL clones express the p150,95 antigen at their cell surface, and that this molecule, like LFA-1, acts at the level of conjugate formation between effector and target cells. PMID- 3106476 TI - Induction of macrophage Ia expression by lipopolysaccharide and Listeria monocytogenes in congenitally athymic nude mice. AB - Experiments were performed to analyze the mechanism by which lipopolysaccharide (LPS) modulates the expression of Ia by murine peritoneal macrophages in vivo. We investigated the effect of LPS on Ia expression in T cell deficient mice by using the congenitally athymic nude mouse model. Injection (i.p) of LPS into athymic (nu/nu) mice resulted in a dramatic increase in the expression and biosynthesis of Ia by peritoneal macrophages 7 days after injection. The magnitude and kinetics of this induction were equivalent to increases observed after LPS injection of euthymic (nu/+) mice. Viable Listeria monocytogenes also increased Ia expression in athymic mice, but in contrast to the induction observed in euthymic mice at 3 and 7 days after injection, increased Ia expression was not seen until 7 days. Ia induction by either LPS or L. monocytogenes in athymic mice was not due to the presence or development of mature T cell function as defined by assays for T cell mitogenesis and interleukin 2 production. We conclude that increased macrophage Ia expression by LPS and L. monocytogenes in vivo can occur in the absence of mature functioning T cells. PMID- 3106477 TI - Dissociation between lymphocyte activation for proliferation and for the capacity to adoptively transfer uveoretinitis. AB - We have shown previously that immunization with bovine interphotoreceptor retinoid-binding protein (IRBP) induces in rats severe eye disease, experimental autoimmune uveoretinitis (EAU). This study examined the uveitogenic capacity of IRBP of another species, the monkey, and tested the cross-antigenicity between these two proteins by a battery of immunological assays. Monkey IRBP was found to be approximately 20 times less uveitogenic in Lewis rats than bovine IRBP. High levels of cross-reactivity between bovine and monkey IRBP were demonstrated by antibodies as measured by the enzyme-linked immunosorbent assay, and by the radiometric ear test of delayed-type hypersensitivity, by using rats immunized with either one of the IRBP. On the other hand, lymphocytes from these rats failed to detect the cross-reactivity between the two IRBP by the proliferation response in culture. Yet, such lymphocytes did recognize the nonimmunizing IRBP when activated in culture for acquiring the capacity to adoptively transfer EAU into naive recipients. The data are discussed with regard to the limited usefulness of the lymphocyte proliferation assay for detection of immunopathogenic processes and the role of cross-reacting antigens in initiation of autoimmune responses. PMID- 3106478 TI - Reversal of advanced murine lupus in NZB/NZW F1 mice by treatment with monoclonal antibody to L3T4. AB - Murine lupus in NZB/NZW F1 (B/W) mice can be prevented by weekly treatment with monoclonal antibodies (MAb) to L3T4 (on "helper/inducer" T cells) if treatment is begun prior to the onset of clinical illness. To determine whether anti-L3T4 could reverse as well as prevent murine lupus, we monitored a cohort of 30 B/W females until age 7 mo, when severe autoimmune disease was established, and then we examined the effects of weekly treatment with MAb to L3T4. The rate of target cell clearance by MAb was considerably slower in old B/W mice than it was in young B/W mice or in normal (BALB/c and C57BL/6) mice. Nonetheless, treatment with anti-L3T4 depleted 90% of circulating L3T4+ cells over 3 mo. In treated mice, the concentration of anti-DNA antibodies fell by 80%, renal insufficiency was reversed, and 1 yr survival was 75% compared to 17% in controls. These findings indicate that L3T4+ cells play an important role in perpetuating murine lupus in B/W mice even after severe disease is present. Because the L3T4 antigen in mice is homologous to the Leu-3/T4 (CD4) antigen in humans, these findings suggest that treatment with CD4 MAb may be effective in people with systemic lupus erythematosus. PMID- 3106479 TI - Susceptibility of astrocytes to class I MHC antigen-specific cytotoxicity. AB - Cell-mediated immune mechanisms contribute to tissue injury within the central nervous system (CNS) in a number of experimental diseases, including experimental allergic encephalomyelitis and some viral infections, and may mediate lesion formation in multiple sclerosis. We investigated the conditions under which murine astrocytes can become susceptible targets of cytotoxic T cells. We demonstrate that mouse astrocytes in vitro can be susceptible targets of class I major histocompatibility complex (MHC)-specific cytotoxicity mediated by L3 cytotoxic T lymphocytes (CTL). Expression of appropriate class I MHC antigen on the astrocytes is a requirement, because only cells bearing the H-2d phenotype are susceptible to lysis by L3 cells. BALB/c-H-2dm2 astrocytes lacking the specific determinant recognized by L3 cells are not susceptible to lysis. Astrocyte lysis can, however, occur under culture conditions in which MHC antigen expression is immunocytochemically low or undetectable. Cytolysis can be inhibited by pretreatment of the effector L3 cells with either anti-Lyt-2 monoclonal antibody (mAb) or anti-clonotypic mAb and by preincubation of the glial target cells with an appropriate anti-H-2 antibody (anti-H-2Ld). mAb to lymphocyte function-associated antigen does not inhibit cytotoxicity of the L3 clone against glial cells. Knowledge regarding the role of CTL within the CNS, including the surface molecules involved in glial cell lysis, could further the development of immunotherapies designed to effect immune reactivity within the CNS. PMID- 3106480 TI - Role of the interleukin 2 receptor in differentiation of a clone of Ly-1+ B cells. AB - CH12.LX, an in vitro subclone of a murine B cell lymphoma that makes IgM reactive with sheep erythrocytes (SRBC), has cell surface receptors for the lymphokine interleukin 2 (IL 2). The binding of recombinant murine IL 2 to these receptors did not stimulate CH12.LX cells to differentiate and secrete antibody. However, the binding of either of two monoclonal antibodies (Mab) specific for the IL 2 receptor increased the proportion of CH12.LX cells that secrete hemolytic IgM. The effect did not require the presence of antigen. One of the Mab, 3C7, is known to block the binding of IL2 to its receptor on T cells, whereas the other, 7D4, which also reacts with the IL 2 receptor, does not block the binding of IL 2. The differentiation of CH12.LX induced by 3C7, but not that induced by 7D4, was inhibited by recombinant IL 2. Neither IL 2 (up to 200 U/ml) nor 3C7 (up to 10 micrograms/ml) had any significant influence on incorporation of [3H]thymidine; 7D4 at 10 micrograms/ml decreased thymidine incorporation by about 60%. Mitomycin C and hydroxyurea, which both inhibit the incorporation of [3H]thymidine into CH12.LX cells, also both induce antibody secretion. In both cases, the concentration necessary to cause differentiation is substantially lower than that needed to cause detectable inhibition of thymidine uptake. We conclude that the IL 2 receptor on CH12.LX cells is a functional signal transducing molecule, and we discuss the possible inverse relationship between proliferation and differentiation. PMID- 3106481 TI - Identification of a rabbit class I-like thymocyte-specific antigen. AB - The availability of a monoclonal antibody, 5E2, has made it possible to characterize a new class I-like thymocyte-specific antigen in the rabbit. Flow cytometry and cyto-fluorescent microscopy show that approximately 70 to 80% of the cells reacting with 5E2 are located throughout the thymic cortex. Structural studies reveal that the cell surface molecule recognized by 5E2 is a non covalently associated heterodimer consisting of a 45,000 dalton glycoprotein and a low m.w. beta-2-microglobulin protein. Certain properties of the 5E2 antigen were similar to the murine TL and human T6 antigens. Therefore we have tentatively assigned to the 5E2 antigen the designation R-Ta on the premise that the structural gene(s) encoding this molecule will be associated with the rabbit major histocompatibility complex. PMID- 3106482 TI - Differential ability of human immunodeficiency virus isolates to productively infect human cells. AB - Isolates of HIV showed distinct differences in the ability to replicate in continuous human hematopoietic cell lines. Moreover, although all PMC cultures obtained from healthy individuals could be infected with HIV, considerable variation in the amount of virus released from different PMC cultures was observed. These biological properties of HIV could not be correlated with clinical state, binding properties of the virus isolates to target cells, or differences in target cell CD4 antigen expression. Some isolates of HIV that could not directly infect the HUT-78 cell line showed productive infection when PMC infected with these viruses were added to this human T cell line. These observations emphasize the importance of cell to cell contact in the spread of virus. The results demonstrate for the first time the differences in the host range specificity of HIV isolates in several individual PMC cultures, and indicate that the optimal isolation of HIV is achieved with normal human PMC rather than established human cell lines. PMID- 3106483 TI - A purified 28,000 dalton protein from Schistosoma mansoni adult worms protects rats and mice against experimental schistosomiasis. AB - We have purified a 28,000 dalton (P28) protein from Schistosoma mansoni adult worms and used it to immunize Fischer rats. Immunofluorescence assays demonstrated that the P28 antigen was mainly located in the parenchyma of the schistosomulum and of the adult worm, including the dorsal spines of the parasite. Western blot analysis revealed that this antigen was present in three species of schistosomes: S. mansoni, S. japonicum, and S. bovis. The antibody response raised against this protein was able to kill S. mansoni schistosomula in in vitro cytotoxicity assays in the presence of rat eosinophils. The inhibition of this cytotoxic activity by an aggregated myeloma IgG2a indicated that one of the major isotypes involved in this in vitro model is IgG2a. The passive transfer of P28 antisera induced a significant level of protection against experimental infection. Moreover, we have immunized Fischer rats and BALB/c mice with the purified 28,000 dalton protein and observed a marked decrease (up to 70%) in the parasite burden in both experimental infection models. PMID- 3106484 TI - Role of c-myc and other genes in interleukin 2 regulated CT6 T lymphocytes and their malignant variants. AB - The cloned murine cytotoxic T cell line CT6 solely requires interleukin 2 (IL 2) for viability and cell cycle progression. Treatment of G arrested cultures of CT6 cells with recombinant IL 2 induces the rapid sequential expression of the nuclear proto-oncogenes c-fos, c-myc, and c-myb but does not affect the expression of several cytosolic or membrane-associated proto-oncogenes. A comparison of early genes induced by growth factor treatment of quiescent NIH/3T3 fibroblasts and CT6 cells demonstrated that only c-fos and c-myc induction is shared in the two different lineages. Factor-independent lines derived from CT6 cells show no mitogenic response to IL 2, yet binding of IL 2 with its receptor in the cells was capable of inducing the expression of c-fos and c-myc. In factor independent cell lines, c-myc was uniformly expressed at high constitutive levels, suggesting that c-myc abrogates growth factor requirements of these cells. The levels of c-myc expression in the factor-independent lines was not due to an autocrine production of IL 2 but may be a consequence of constitutively activated IL 2 receptors. PMID- 3106485 TI - Reaction of T lymphocytes with anti-T3 induces translocation of C-kinase activity to the membrane and specific substrate phosphorylation. AB - Reaction of the T cell membrane with monoclonal antibodies to T3 can initiate cellular activation, and this is associated with increased intracellular Ca2+ and inositol-trisphosphate (IP3) release. We therefore studied the possible involvement of Ca2+/phospholipid-dependent kinase (C-kinase) in these phenomena. Quantitative assays of exogenous substrate phosphorylation in unstimulated cells showed Ca2+/phospholipid-dependent kinase activity in the cytosol, but no comparable activity in the particulate fractions corresponding to membrane and cytoskeleton material. At concentrations of soluble anti-T3 that partially activate T cells in the absence of macrophages, there was a 50 to 60% decrease in C-kinase activity in the cytosol, with a comparable increase in activity in the membrane fraction. A similar transfer of activity was also induced with the known C-kinase activator, 12-O-tetradecanoyl-phorbol-13-acetate, although redistribution was more rapid in onset, more complete, and more sustained. Redistribution of enzyme activity was additionally confirmed by qualitative assays of endogenous substrate phosphorylation. Labeling of intact cells followed by immunoprecipitation analysis with anti-T3 indicated signal-dependent phosphorylation of two components of the T3 complex and an unidentified 94,000 substrate that was resistant to reduction and alkylation. These findings are consistent with an important role for C-kinase in transduction of membrane events by the T3-Ti complex. PMID- 3106486 TI - Switch region content of hybridomas: the two spleen cell Igh loci tend to rearrange to the same isotype. AB - We have examined the switch region content of 25 hybridomas that secret antibodies of various isotypes with specificity for phosphocholine or glycoproteins of herpes simplex virus. These Southern hybridization experiments included probes for the murine JH region as well as probes for the mu, gamma 3, gamma 1, gamma 2b, gamma 2a, and alpha switch regions. For 22 of the hybridomas, the deletion model of the heavy chain switch fits the data well--all switch regions upstream of the rearranged (and expressed) switch regions are deleted and all switch regions downstream remain in the germline configuration. As exceptions to a simple deletion model of the switch recombination, we have observed two, and perhaps three, examples of switch region rearrangements downstream of an expressed heavy chain gene. The 25 hybridoma DNA samples include 28 rearranged gamma switch regions; the sizes of at least 25 of these rearranged fragments are consistent with recombination in the tandemly repeated sequences associated with gamma genes. For those hybridomas with two spleen cell-derived Igh loci, including three mu-expressers, three gamma 3-expressers, four gamma 1-expressers, and one gamma 2b-expresser, the two loci tend to be rearranged to the same switch region, suggesting that the heavy chain switch rearrangement is an isotype specific event. The exceptions within this group include three hybridomas in which the switch seems to be incomplete--on one chromosome the JH complex is rearranged to the S gamma 3 region, while on the other it remains associated with the S mu region. A second group of hybridomas, which includes four gamma 3 expressers, have both gamma 3 and gamma 1 switch rearrangements. Each of these four hybridomas includes three rearranged JH segments, suggesting that they may be the result of an unusual differentiative pathway or a technical artifact. These experiments suggest that the heavy chain switch rearrangement in normal spleen cells is a deletion event that occurs within tandemly repeated elements. The rearrangement is mediated by factors with partial, or perhaps complete, isotype specificity. PMID- 3106487 TI - Suppression of Ia-unrestricted primary anti-Qa-1 cytotoxic T lymphocyte responses by class II major histocompatibility complex-restricted cellular interactions. AB - A model has been established for investigating the cellular interactions for the generation and regulation of primary cytotoxic T lymphocyte (CTL) responses to Qa 1 alloantigens. Although NZB anti-BALB/c one-way mixed leukocyte cultures (MLC) generate anti-Qa-1b CTL, anti-Qa-1 CTL responses are not generated during BALB/c anti-NZB one-way MLC or during two-way MLC with NZB and BALB/c spleen cells. However, depletion of L3T4+ cells from the spleens of BALB/c mice before two-way MLC with NZB spleen cells resulted in anti-Qa-1b CTL responses. Likewise, the addition of anti-L3T4 monoclonal antibody (mAb) or anti-I-Ad mAb to two-way MLC with NZB and BALB/c spleen cells resulted in the generation of anti-Qa-1b CTL. Conversely, anti-Lyt-2 mAb inhibited the generation of anti-Qa-1 CTL. These data indicate that class II major histocompatibility complex-restricted cellular interactions are capable of suppressing the generation of Ia-unrestricted anti-Qa 1 CTL responses by Lyt-2+ responder cells. This model provides a novel opportunity to both characterize the cellular interactions responsible for regulating primary CTL responses to the Qa/Tla-encoded class I molecule Qa-1, and determine the contribution of this L3T4+ Ts-dependent defect in NZB mice to the pathogenesis of autoimmunity. PMID- 3106488 TI - Inhibitory effects of anti-interleukin 2 receptor and anti-L3T4 antibodies on delayed type hypersensitivity: the role of complement and epitope. AB - Although it is often assumed that anti-T cell antibodies mediate immunosuppression by targeting T cells for destruction, other activities should be considered. To dissect the mechanisms by which anti-L3T4 and anti-interleukin 2 receptor (IL 2R) monoclonal antibodies (Mab) mediate immunosuppression, the effects of anti-L3T4 and two complement-fixing anti-IL 2R Mab of the same isotype, but defining functionally distinct epitopes, were probed in a delayed type hypersensitive (DTH) model using BALB/c as well as two C5-deficient mouse strains. Low doses of anti-L3T4 and the M7/20 anti-IL 2R Mab, which competitively blocks IL 2 binding, inhibit DTH in BALB/c mice whereas an anti-receptor antibody which does not block the IL 2 binding site did not effectively abrogate DTH. Interestingly, anti-L3T4, but not M7/20 anti-IL 2 Mab treatment blocked DTH in the C5-deficient strains. On the other hand, M7/20 does not cause immunosuppression solely by blocking the IL 2R from occupancy by IL 2 because binding to T blasts by M7/20 is equivalent in BALB/c and C5-deficient strains. Consequently, immunosuppression mediated by anti-IL 2R Mab is dependent on both IL 2 receptor site blockade and C5. Clearly, anti-L3T4 and M7/20 have disparate requirements for C5 in mediating immunosuppression. There can be no doubt that factors other than the cellular targeting patterns influence the immunosuppressive activities of Mab. Ideally, anti-T cell Mab should fix complement and inhibit T cell function. PMID- 3106489 TI - CD5 antibodies increase intracellular ionized calcium concentration in T cells. AB - The binding of a variety of monoclonal antibodies to the CD5 (T, gp67) pan T cell differentiation antigen has been shown to potentiate T cell proliferation. In this paper we show that CD5 monoclonal antibodies cause increased intracellular free calcium concentration ([Ca2+]i) in T cells. An increase in [Ca2+]i occurred within 1 min in indo-1-loaded PBMC after the addition of CD5 monoclonal antibodies and cross-linking with a second step anti-mouse kappa light chain antibody. Cross-linking of CD5 was effective when done directly on the cell surface or by the administration of preformed soluble complexes that contained CD5 antibodies. Calcium mobilization induced by suboptimal concentrations of CD3 antibodies was specifically augmented and sustained by CD5 antibodies, although the enhancement was modest in magnitude. When cell surface phenotype was correlated with calcium mobilization, it was found that the CD5 response was restricted to CD5+/CD3+ cells, and that approximately 90% of CD5+ cells had responded. CD5-induced calcium mobilization was found to differ from CD3 stimulation in that EGTA entirely ablated the CD5 response, whereas the CD3 response was resistant to EGTA, indicating that the CD5-induced increased [Ca2+]i is derived primarily or entirely from extracellular calcium. CD5-stimulated calcium mobilization also differed from CD3 in that the CD5 response was inhibited by pretreatment with phorbol myristate acetate, whereas the CD3 response was not, suggesting that depletion of protein kinase C causes an uncoupling of signal transduction between CD5 and calcium channels. Finally, experiments were done with T cells after antigenic modulation of the CD3 or CD5 molecules. Unexpectedly, both the CD5 and the CD3 responses were ablated on CD3 modulated cells, whereas only the CD5 response was ablated on CD5-modulated cells. In addition, several Cd5+/CD3- T cell leukemia lines also failed to respond to CD5 stimulation, providing further evidence which indicates that the CD5 response depends on the cell surface expression of CD3 or a CD3-associated structure. These findings suggest that one mechanism for CD5-induced augmentation of mitogen-stimulated T cell proliferation involves increased [Ca2+]i which is distinct from but interdependent with that induced by stimulation of the CD3 molecule. PMID- 3106490 TI - Human T cell clones use a CD3-associated surface antigen recognition structure to exhibit both NK-like and allogeneic cytotoxic reactivity. AB - In the present study, we developed human non-MHC-restricted CTL clones from human peripheral blood mononuclear cells activated in vitro with recombinant IL 2 and subsequently expended with PHA. The CD3/Ti+ clones were selected for their ability to exhibit non-MHC-restricted CTL reactivity by killing various tumor cell lines in culture, including the line K562 which does not express MHC antigens. We report that, at least for some of the NK-like T cell clones, it is possible to establish an allo-CTL activity, and that the CD3-associated surface antigen recognition structure might be involved in both reactivities. PMID- 3106491 TI - Interferon blocks interleukin 1-induced prostaglandin release from human peripheral monocytes. AB - We have studied the short-term effects of interleukin 1, lipopolysaccharide, and interferon on prostaglandin release from freshly isolated human peripheral monocytes. When the cells were pretreated for 8 to 9 hr with either E. coli lipopolysaccharide or recombinant interleukin 1 (beta), prostaglandin release increased. Inclusion of recombinant IFN-alpha or IFN-gamma during the pretreatment phase blocked subsequent prostaglandin release. Interferons were effective at concentrations in the range of 1 to 10 antiviral units/ml, and the inhibition was manifested within several hours after exposure to the lymphokine. Similar trends were observed by measuring thromboxane release. These data suggest antagonistic roles for interleukin 1 and interferon in the regulation of eicosanoid release from monocytes. PMID- 3106492 TI - M241 (CD1) expression on B lymphocytes. AB - The human thymus leukemia-like antigens (CD1a-c) consist of three similar glycoproteins found on subpopulations of normal thymocytes, T cell acute leukemias, and cutaneous dendritic cells. The CD1c antigen recognized by the M241 monoclonal antibody was detected on the circulating mononuclear cells of three children with severe combined immunodeficiency disease (SCID). Two-color immunofluorescence analysis demonstrated that M241 expression (43 to 95%) was limited to cells expressing the B cell-restricted antigens B4 (CD19), B1 (CD20), and surface immunoglobulin. To confirm M241 expression on normal cells of the B lineage rather than aberrant expression limited to SCID B cells, its expression was demonstrated serologically and biochemically on purified B cells from spleen, tonsil, and peripheral blood. Parallel analyses with monoclonal antibodies NA1/34 and 4A76 demonstrated that the CD1a and CD1b molecules were negative on all B cells that were studied. It has been hypothesized that the CD1 molecules represent the human counterpart of the murine thymus leukemia antigens due to their similar size, limited tissue distribution, and association with beta 2 microglobulin. This study suggests that a subset of CD1 antigens detected by M241 (CD1c) may represent a human analog of a murine Qa antigen due to its extended distribution on normal peripheral B cells. PMID- 3106493 TI - Expression of functional IL 2 receptors by lipopolysaccharide and interferon gamma stimulated human monocytes. AB - Human peripheral blood monocytes were stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) alone or in combination. Stimulated but not resting monocytes displayed the Tac peptide of the interleukin 2 (IL 2) receptor within 24 hr as measured by immunofluorescence staining and [3H] Tac binding. The total number of anti-Tac binding sites on co-stimulated monocytes was 13,700. By using scatchard analysis with radiolabeled IL 2, the activated cells were shown to express low numbers (below 100 sites/cell) of high affinity binding sites with a KD of approximately 15 pM. LPS and IFN-gamma were additive in augmenting the number of IL 2 and anti-Tac binding sites. By using an ELISA assay specific for the soluble released form of the Tac peptide we identified 112 U/ml of IL 2 receptors in the supernatant of monocytes stimulated for 24 hr with IFN-gamma, 233 U/ml after stimulation with LPS, and 519 U/ml after the addition of both stimulating agents. Both the membrane form (55,000 daltons), as well as the soluble form (45,000 to 50,000 daltons) of the Tac, IL 2 receptor, peptide from monocytes were shown by immunoprecipitation and gel electrophoresis to be similar size to the comparable forms of these receptors derived from activated T cells. In addition, monocytes stimulated for 8 hr contained mRNA specifically hybridizing to a cDNA probe coding for the Tac peptide. Finally, activated monocytes responded to the addition of recombinant IL 2 by an increase in H2O2 production that was measured by using fluorescent indicator 2,7 dichlorofluorescein. This response as well as the observed induction of monocytic IL 2 receptors by LPS may point to a functional role for this receptor during monocyte/macrophage responses to microbial infections. PMID- 3106494 TI - The production of tumor necrosis factor by mouse bone marrow-derived macrophages in response to bacterial lipopolysaccharide and a chemically synthesized monosaccharide precursor. AB - Lipid X, a monosaccharide biosynthetic precursor of lipid A, has been chemically synthesized and was shown to induce bone marrow-derived macrophages to release tumor necrosis factor (TNF) in vitro. However, relatively high amounts of lipid X were necessary for induction, and the levels of TNF were much less than those induced by small amounts of lipid A itself or LPS. Lipid X prepared by extraction of Escherichia coli mutants induced higher levels of TNF than the chemically synthesized material, but this is probably partially due to amounts of impurities in the extracted material. Pretreatment of macrophages with IFN-gamma resulted in the release of higher amounts of TNF on subsequent induction with either LPS or lipid X. In contrast, pretreatment of macrophages with LPS induced hyporesponsiveness for TNF production on subsequent rechallenge with LPS. Lipid X, on the other hand, was incapable of making macrophages hyporesponsive for TNF production. PMID- 3106495 TI - Cell matrix adhesion-related proteins VLA-1 and VLA-2: regulation of expression on T cells. AB - The mitogens phytohemagglutinin (PHA) and concanavalin A inhibited the appearance of the very late activation antigen (VLA)-1, but did not inhibit VLA-2 expression on cultured activated T cells. In contrast to diminished VLA-1 expression, mitogen treatment caused increased cell surface expression of other activation antigens such as T10, HLA-DR, interleukin 2 (IL 2) receptor, and 4F2, and greater cell proliferation. Conversely, when T cells were not repetitively restimulated with mitogen, these less proliferative "postactivated" T cells had elevated VLA-1 expression. The diminished expression of VLA-1 caused by PHA was reversible since subsequent removal of mitogen was associated with increased VLA-1, paralleled by a decrease in interleukin 2 receptor levels. In addition to preventing or delaying the initial appearance of VLA-1, PHA stimulation also was somewhat effective in causing the disappearance of VLA-1 already present, especially on recently established cultures. However, cultures that had either never seen PHA, not seen PHA for several weeks, or been stimulated regularly with PHA, but were several months old, did not lose VLA-1 in response to PHA stimulation, suggesting that a state of insensitivity to PHA effects could be attained. Unlike PHA stimulated T cells, T cells repetitively restimulated with alloantigen or the monoclonal antibody T3 did not show a marked absence of VLA-1 but rather showed an increased level of VLA-2 relative to VLA-1. Taken together, results of stimulation by either mitogen, alloantigen, or anti-T3 monoclonal antibody support the conclusion that T cell stimulation in general can cause a decreased VLA-1:VLA-2 ratio, whether by decreased VLA-1 or increased VLA-2. These shifts in VLA-1:VLA-2 ratios are probably not simply the result of shifts in the relative proportions of different subpopulations, because similar growth-related changes in this ratio were observed on the T cell line ANITA, which is a homogeneous population of cells. Because both VLA-1 and VLA-2 are differentially regulated on cultured, long term activated T cells depending on stage of activation and growth conditions, and are members of a family of at least five heterodimers that includes cell matrix adhesion molecules, we suggest that these studies will provide clues to novel aspects of T cell growth regulation, perhaps relating to T cell-matrix adhesion. PMID- 3106496 TI - Mycobacterium leprae antigen-induced suppression of T cell proliferation in vitro. AB - The extent to which M. leprae and its products induced suppression of T lymphocyte proliferation in vitro was evaluated. M. leprae antigens suppressed T cell proliferation in response to mitogens and antigens in both lepromatous and tuberculoid patients, as well as controls never exposed to M. leprae or M. leprae endemic areas. Both soluble and particulate fractions of M. leprae were found to suppress proliferation in a dose-dependent manner. The extent of suppression was inversely related to the proliferative response of the donors mononuclear cells to M. leprae. Evidence indicates that M. leprae contains both stimulatory and suppressive molecules for T cells. One such suppressive antigen, Lipoarabinomannan (LAM)-B of M. leprae, also suppressed the proliferative response of tuberculoid patients. Suppression was also observed with the LAM-B of M. tuberculosis. The suppressive effects observed were not due to the toxicity of the antigen. Some of the suppressive activity was mediated by T8+ suppressor cells and was expressed in both lepromatous and tuberculoid patients. We suggest that previous sensitization to M. leprae and other cross-reactive mycobacterial antigens determines the sensitivity of T cells to the suppressive effects of M. leprae antigens. PMID- 3106497 TI - Immunoglobulin variable region heptamer-nonamer recognition sequence joined to rearranged D-J segment: implications for the immunoglobulin recombinase mechanism. AB - We have found a novel immunoglobulin gene rearrangement in a murine hybridoma in which a heavy chain variable region (VH) heptamer-nonamer recognition sequence is joined to the diversity segment (D) through head-to-head fusion. The heptamer nonamer recognition sequence and its adjacent 5' DNA are derived from the downstream flanking region of a germline VH gene. Sequence analysis indicates that this adjacent DNA is homologous to the downstream flank of VH108B, and it has characteristics of RNA processing that may suggest it was derived from an mRNA intermediate; these unusual features indicate that the segment is a processed gene. Because of head-to-head fusion, the recognition sequence and the flanking sequence are in opposite transcriptional polarity to D. The latter is joined correctly at its 3' border to a joining (J) gene segment. A gamma 1 constant region (but not mu) is located further downstream. Thus this fragment has several features common to normal immunoglobulin heavy chain gene rearrangement despite the unusual joining event involving V-D. Linkage of the VH heptamer-nonamer recognition sequence to D has not been observed previously. Although the recognition sequence described is inverted with respect to D and J, the endonucleolytic process that cleaved the recognition sequence at the 5' border of the heptamer before rearranging it to D was accurate. We suggest that of the three functions associated with the recombinase reaction; recognition, cutting, and ligation, only recognition and cutting may be limited to specific structures, and the ligation step may be less restricted because it is not confined to forming coding-to-coding or flank-to-flank joints. This aberrant ligation product suggests that the information leading to normal rearrangements may be found in structures that include more than the recognition sequences or coding regions alone, because the joining described here has spliced the incorrect end of a recognition sequence to a coding region to yield a nonproductive recombination. PMID- 3106498 TI - Somatic evolution of diversity among anti-phosphocholine antibodies induced with Proteus morganii. AB - The variable region sequences of light and heavy chains (VL and VH) were determined for 11 hybridoma antibodies produced in response to the PC moiety on Proteus morganii. These hybridomas were derived from two separate fusions, one obtained from mice early in a secondary response and the other from late in a secondary response. All of these antibodies possessed a cross-reactive idiotype found on anti-PC antibodies in the M603 family, and exhibited preferential specificity for PC in the context of P. morganii. We found that all of the antibodies were derived from a single VH/VL pair. VH was encoded by V1, DFL16.1 and JH1, and VL was encoded by a consensus VK8 gene and JK5. Antibodies differed from each other by somatic point mutations that occurred at a high rate. The mutations in VL were approximately one-third as abundant as those in VH and were randomly distributed throughout the molecule. Mutations in VH were concentrated in CDR 2 and 3 and had a replacement to silent ratio that was three to six times greater than predicted from random accumulation. Based on the sequence data, a single genealogic tree with multiple branches could accommodate all the hybrids from a fusion. We concluded that in both examples the anti-PC response arose by somatic mutation and stepwise selection from a single precursor. Antigen binding studies with these 11 hybridomas and a 12th that had no mutations revealed that the acquisition of preferential specificity for antigen was dependent on somatic mutation of germline genes. Additional binding studies demonstrated that continued selection during clonal expansion was probably antigen driven. An unexpected finding was five independently selected antibodies from one fusion that had identically mutated VH and VL sequences. We suggest that the hypermutation mechanism is not a continuously active process during clonal expansion and that it is regulated, probably during the mid to late phase of the primary response. PMID- 3106499 TI - Re.: The analysis of natural killer cell subpopulations by a double marker method. PMID- 3106500 TI - Separation of human IgA1 and IgA2 using jacalin-agarose chromatography. AB - A lectin isolated from the tropical jackfruit, jacalin, previously reported to precipitate human immunoglobulin A (IgA), and conjugated to agarose was used to separate the two subclasses of IgA from secretions. Jacalin-agarose binds specifically to the D-galactose moiety of IgA1 but not to IgA2 which has a different carbohydrate content and structure. IgA2 passed through the jacalin agarose column and was collected in the void volume. IgA1 was eluted from the lectin by 0.8 M galactose. Of a representative diluted anti-alpha chain-purified colostral IgA preparation containing 50.2 micrograms IgA1 and 55.8 micrograms IgA2, 40.3 micrograms IgA1 (80.3% of the original) and 49.6 micrograms IgA2 (88.9%) was collected following jacalin-agarose chromatography. The jacalin purified IgA1 fraction contained 8.0% IgA2 and the IgA2 fraction contained no IgA1. In addition, the IgA1 and IgA2 fractions had naturally occurring antibody activity to a normal oral bacterium. The method is easy, reproducible and specific and has many applications to mucosal immunological investigations. PMID- 3106501 TI - Quantitation of free kappa light chains in serum and urine using a monoclonal antibody based inhibition enzyme-linked immunoassay. AB - The murine monoclonal antibody K-1-21 with specificity for free but not heavy chain-associated kappa chains was used to develop an inhibition enzyme immunoassay for quantitation of free kappa chains in serum and urine. The assay utilizes a biotin conjugate of the monoclonal antibody and has an effective working concentration range of 0.5-50 micrograms/ml free kappa chain. Normal serum and urine yielded mean values of 1.2 and 4.9 micrograms/ml respectively using this assay system. Serum levels in patients with kappa chain myelomatosis ranged from 2 to 1700 micrograms/ml while serum from patients with lambda chain malignancies exhibited normal free kappa chain levels. The importance of the ability to readily quantitate light chains in serum was demonstrated by the finding in one patient of an absence of free kappa chains in the urine despite elevated levels of serum kappa chains. A significant drop in serum-free kappa chain levels was observed in this patient following a course of chemotherapy. The assay should prove valuable in the diagnosis, prognosis and monitoring of B cell neoplasias characterized by free kappa light chain secretion. PMID- 3106502 TI - A new assay for interleukin-1 in the presence of interleukin-2. AB - A simple and reliable assay for interleukin-1 (IL-1) is described which has the advantage over other assays that it is independent of interleukin-2 (IL-2) production by the test cells. The assay makes possible the detection of IL-1 in the supernatants of T cell populations. The ability of IL-1 to induce IL-2 receptor expression in the absence of T cell mitogen is the basis of this assay. Thus, proliferation of mouse thymocytes incubated in the presence of saturating concentrations of IL-2 (10 U/ml) was directly dependent on the concentration of IL-1. The sensitivity of the assay is comparable to the sensitivity of the classical thymocyte co-stimulator assay. Natural and recombinant human and murine IL-1 were measured in this test system with comparable sensitivity. PMID- 3106503 TI - Measurement of human factor VIII by avidin-biotin dot immunobinding ELISAs. AB - Hemophilia A is a congenital bleeding disorder which is characterized by a functional deficiency of the coagulation protein factor VIII. We have developed sensitive enzyme-linked immunosorbent assays (ELISAs) for measuring the antigenic reactivity of factor VIII. The assays utilize dot immunobinding techniques, commercial monoclonal antibodies, and a detection system enhanced by the interaction of avidin and biotin. The dot immunobinding ELISAs were optimized for measuring factor VIII in normal and hemophilic plasma, and in partially and highly purified preparations of factor VIII. Linear standard curves were established for all samples, defining the range for accurate measurement. Factor VIII was detected at concentrations as low as 0.0005 U/ml, which represents 0.1 pg of protein. PMID- 3106504 TI - Quantitative enzyme-linked immunosorbent assay (ELISA) for non-enzymatically glycated serum protein. AB - A competitive ELISA for quantitative determination of glucitollysine, the reduced hexose alcohol form of glucose conjugated to the epsilon amino group of lysine was developed. We applied it to measure non-enzymatically glycated serum proteins. The antiserum obtained by immunizing guinea pigs with reductively glycated human albumin was capable of identifying and quantitating glucitollysine residues of serum proteins in normal and diabetic subjects after reduction of the proteins with sodium borohydride. The ELISA assay developed here had satisfactory reproducibility as judged by the intra-assay precision of 2.3-7.6% and the interassay precision of 6.7-9.8%. Results from this assay procedure correlated well with those from the radioimmunoassay and the boronate affinity chromatography procedure. The data suggested that diabetic serum proteins contained at least three times as much immunochemically detectable glucitollysine residues as normal serum proteins after reduction of the proteins with sodium borohydride. This method allows to quantitate glucitollysine residues on any of the proteins that have been implicated in the pathological sequelae of diabetes. PMID- 3106505 TI - Enteric encephalopathy. PMID- 3106506 TI - Acute schistosomiasis (Katayama fever): clinical deterioration after chemotherapy. PMID- 3106507 TI - Factors influencing susceptibility to meningococcal disease during an epidemic in The Gambia, West Africa. AB - A study was made of factors that influenced susceptibility to group A meningococcal disease during an epidemic that affected The Gambia, West Africa during the dry season of 1982-83. No explanations were found for the distribution of cases between villages or within affected villages. Socio-economic status, crowding, nutrition and previous exposure to meningococcal disease all appeared to be unimportant. Examination of serum samples obtained before the outbreak from a few children who subsequently became patients and from an equal number of age matched controls from the same village showed a higher mean serum IgA value in children who became patients than in controls. There were not, however, any significant differences found in the concentrations of IgG, IgM, complement or meningococcal antibody between the two groups. Four children who developed culture-proven group A meningococcal disease had raised titres of bactericidal antibody to the epidemic strain 2-3 months before their illnesses. Our findings suggest that some important risk factors for group A meningococcal disease remain to be identified. PMID- 3106508 TI - A novel synthetic vitamin A-like compound (a polyprenoic acid derivative, E-5166) inhibits the release of arachidonic acid stimulated by epidermal growth factor. AB - Little is known about the mechanisms of anti-inflammatory activity of retinoids. A new synthetic vitamin A-like compound (polyprenoic acid derivative, E-5166) has a strong in vitro binding affinity to intracellular binding proteins for acidic retinoids. In order to elucidate the anti-inflammatory activity of E-5166, we studied the effect of E-5166 on the epidermal growth factor (EGF)-stimulated arachidonic acid (AA) release of pig epidermis. E-5166 significantly inhibited the EGF-stimulated AA release and this inhibitory effect of E-5166 required a longer incubation than hydrocortisone did. Furthermore, E-5166 inhibited the EGF stimulated phosphatidylinositol (PI) turnover of pig epidermis. These results indicate that E-5166 inhibited the EGF-stimulated AA release through the inhibition of the EGF-stimulated PI turnover. PMID- 3106509 TI - Evaluation of epidermal cell kinetics following freezing or wounding of mouse skin and their potential as initiators of carcinogenesis. AB - It has been shown that abrasion, and consequent regenerative hyperplasia, acts as a promoting agent in mouse skin carcinogenesis. The present experiments were designed to evaluate the possibility that ulceration and its consequent regeneration might also act as initiators. Female Sencar mice were used, and ulceration was induced either by the application of a frozen rod or by incision of the skin of the back. The time course of the ulceration, regeneration, and repair of the mouse skin following ulceration by either method was evaluated utilizing morphologic and autoradiographic techniques. The labeling index of the epidermis, using [3H]-thymidine and autoradiography, reached a maximum level 7 days after ulceration and the epidermal hyperplasia was most pronounced at days 7 14. The potential initiating activity of freeze ulceration or incision was evaluated by performing these procedures on 7-week-old female Sencar mice followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) applied twice a week to the ulcerated areas, 5.2 micrograms in each application. Extending the total experimental observation to 1 year indicated that freeze ulceration and incision did not initiate carcinogenesis in the mouse skin when promoted with TPA. PMID- 3106510 TI - beta-Lactamase production in experimental endocarditis due to aminoglycoside resistant Streptococcus faecalis. AB - We used a beta-lactamase-producing (beta L+) strain of Streptococcus faecalis that also had high levels of resistance to all aminoglycosides to induce experimental endocarditis in rats. The rats were treated for five or 10 days with procaine penicillin, vancomycin, gentamicin, rifampin, or ciprofloxacin (alone or in various combinations), or with penicillin plus clavulanic acid. The levels of penicillin in serum and vegetations declined rapidly in the beta L+-infected rats treated with procaine penicillin alone, unlike the sustained levels of penicillin in either beta L- -infected rats treated with procaine penicillin or beta L+ infected rats treated with penicillin plus clavulanic acid. For the beta L+ infected rats, the enterococcal counts in vegetations were significantly reduced (greater than 3 log10 cfu/g) only by vancomycin and by penicillin plus clavulanic acid. The efficacy of the latter regimen probably resulted from the inhibition of penicillin inactivation by clavulanic acid in vegetations infected with the beta L+ strain. Our in vivo findings document the biologic significance of beta lactamase production. PMID- 3106512 TI - Isolation of Mycoplasma pneumoniae from bronchoalveolar lavage fluid. PMID- 3106511 TI - Killing of Neisseria meningitidis by human neutrophils: implications for normal and complement-deficient individuals. AB - The contributions of complement-dependent phagocytosis and serum bactericidal activity (SBA) to the killing of 62 strains of meningococci were examined by using C8-depleted or pooled human serum (PHS). The complement-dependent nature of killing by neutrophils was confirmed by restoring survival to control values by using heated serum. Serogroups B and 29E, but not A, C, Y, and W135, were ingested and killed by neutrophils in C8-depleted PHS (PHS-C8Dep; 41.7% +/- 7.3% and 60.5% +/- 17.8% vs. greater than or equal to 100% survival, respectively, at 30 min). Group B meningococci were resistant to complement-mediated SBA, whereas group Y were susceptible. Deposition of C3 on serogroups B and Y was similar (28.5 +/- 2.9 vs. 23.5 +/- 2.7 C3 fluorescence units; P greater than .05); however, susceptibility to complement-dependent phagocytosis and complement mediated SBA of serogroups B and Y did not correlate. We also examined meningococcal phagocytosis by using serum from a C8-deficient patient. In contrast to PHS-C8Dep, this serum supported rapid phagocytic killing of serogroups A, C, Y, and W135 meningococci. This finding suggests that vaccinating individuals deficient in late-complement components may shift the burden of host defense from SBA to phagocytosis. PMID- 3106513 TI - Development of resistance after beta-lactam therapy. PMID- 3106514 TI - Biphasic effect of vanadium salts on in vitro tumor colony growth. AB - Vanadium is a trace element widely distributed in nature. It interferes with a variety of enzyme systems and is also reported to increase DNA-synthesis and in vitro clonal growth of human and mouse fibroblasts. The purpose of the present study was to determine the effect of vanadium salts on the in vitro growth of fresh human tumor specimens. Various concentrations of ammonium metavanadate (AMV), vanadyl sulfate trihydrate (VST) and ortho sodium vanadate (OSV) were tested in a human tumor cloning assay (HTCA). Thirty-four evaluable specimens were tested at concentrations of less than or equal to 10(-10) M of one or more vanadium salts. At this concentration, colony formation was increased by greater than or equal to 150% as compared to control at one or more concentrations in 16 specimens (47%). Twelve evaluable specimens were tested against various concentrations greater than 10(-10) M. Colony formation was inhibited by greater than or equal to 50% of the control at one or more concentrations in all specimens. In further experiments we performed a head-to-head comparison of OSV (10(-3)M) and our standard positive control for cell kill (chromomycin A3, 100 micrograms/ml) in 34 specimens. OSV led to a comparable or better cell kill in 28 tumors (82%). We conclude that vanadium salts at low concentrations (less than or equal to 10(-10)M) can stimulate in vitro colony formation from human tumors. At higher concentrations (greater than 10(-10)M) tumor colony formation is inhibited. OSV might be useful as a very inexpensive positive control in the HTCA. In addition, the value of vanadium salts as antitumor agents should be further investigated in vivo. PMID- 3106515 TI - Nycteria medusiformis Garnham and Heisch, 1953: a malaria parasite of the Egyptian insectivorous bat, Taphozous perforatus. PMID- 3106516 TI - Prevalence of bilharziasis among children in Gharbia Governorate, Egypt. PMID- 3106517 TI - The rheumatoid factor in human schistosomiasis. PMID- 3106518 TI - Markers and subpopulations of T lymphocytes in schistosomiasis. PMID- 3106519 TI - Immunoglobulin levels and intensity of infection in patients with fascioliasis, single or combined with schistosomiasis. PMID- 3106520 TI - The diagnostic importance of intraepithelial lymphocytes in some colonic diseases in Egypt. PMID- 3106521 TI - Serological studies of the antigens prepared from Biomphalaria glabrata snails infected and uninfected with Schistosoma mansoni. I. Indirect immunofluorescent antibody test using infected snail and adult worm antigens. PMID- 3106522 TI - Treatment of murine interferon-alpha/beta-sensitive and -resistant friend leukemia cells with tumor necrosis factor in combination with murine interferon alpha/beta or -gamma. AB - Interferon-alpha/beta (IFN-alpha/beta)-sensitive (FLC 745) and -resistant (FLC 3Cl8) Friend leukemia cells (FLC) were fairly refractory to the cytotoxicity of murine tumor necrosis factor (MuTNF) in vitro. Both lines became highly sensitive to mTNF when treated in combination with murine IFN-gamma; when treated with IFN alpha/beta, only the FLC 745 became sensitive to MuTNF. Romeo et al. have reported previously that an antiviral state was induced in both FLC lines by IFN gamma, but only in FLC 745 by IFN-alpha/beta. The present results suggest that the sensitivity to the synergistic cytotoxic effect of IFN and TNF in these cells is correlated with the ability to be induced into an antiviral state. PMID- 3106523 TI - Structure and activity of recombinant human interferon-gamma analogs. AB - We have prepared interferon-gamma (IFN-gamma) analogs to study the structural role of particular amino acids in relation to their effects on antiviral activity. Three IFN-gamma analogs were prepared on the basis of predicted secondary structure. In two of the analogs, [Gln25]IFN-gamma and [Thr45]IFN gamma, changes were made at residue 25 (Asn to Gln) and at residue 45 (Met to Thr), respectively. [Gln25Lys78]IFN-gamma had two changes, at residue 25 (Asn to Gln) and residue 78 (Asn to Lys). Another analog, [Cys-Tyr-Cys]IFN-gamma, incorporated Cys-Tyr-Cys at the amino terminus. Comparison of the structure and activity of these analogs with that of the natural sequence protein suggested that residues 25 and 78 are at the protein surface and play an important role in antiviral activity. The residue at position 45 was found to be important for maintaining the protein structure, as assessed by circular dichroism spectroscopy. The addition of Cys-Tyr-Cys resulted in a small perturbation of protein structure and a small decrease in antiviral activity. PMID- 3106524 TI - Pharmacokinetic studies with human and rat interferons-gamma in different species. PMID- 3106526 TI - Interferon-gamma enhances biosynthesis of pterins in peripheral blood mononuclear cells by induction of GTP-cyclohydrolase I activity. AB - In a recent publication, evidence was presented that cellular immune responses are associated with increased in vivo and in vitro excretion of neopterin. Our study aimed at investigating the biosynthesis of unconjugated pterins in highly purified human macrophages and T lymphocytes before and during stimulation with supernatants of activated T cells or with recombinant human interferon-gamma (IFN gamma) by monitoring the following parameters: substrate concentration (GTP, guanosine triphosphate), activity of the enzyme initiating the biosynthesis of pterins (GTP-cyclohydrolase I) and product concentrations of total neopterin, biopterin, and pterin. In contrast to T cells and other tissues, macrophages were unable to produce tetrahydrobiopterin. This was indicated by our failure to detect biopterin and pterin. Instead, products of the first biosynthetic step accumulated, which were measured as total neopterin. We concluded that in macrophages the other enzymes required for biosynthesis of tetrahydrobiopterin are limiting. GTP concentration correlated with GTP cyclohydrolase I activity. An increase in both was induced by IFN-gamma and suppressed by neutralization of T cell supernatants with monoclonal antibodies having specificity for IFN-gamma. Addition of tetrahydrobiopterin to the culture medium only led to a suppressed increase in GTP cyclohydrolase I activity and neopterin, but not in GTP concentration. Thus, it appears that IFN-gamma selectively stimulates the early steps of pterin biosynthesis in macrophages, thereby leading to accumulation and excretion of dihydroneopterin and neopterin. Although the physiological role of this phenomenon remains obscure, the fact that it seems to reflect endogenous release of IFN-gamma deserves particular attention. PMID- 3106525 TI - Structure and activity of glycosylated human interferon-gamma. AB - Structural properties and activity of recombinant human interferon-gamma (IFN gamma) purified from Chinese hamster ovary (CHO) cells or a natural source were determined and compared with those of Escherichia coli-derived IFN-gamma. One preparation of CHO-derived IFN-gamma showed three bands, with the middle band being a doublet, in a SDS-polyacrylamide gel. The two higher-molecular-weight bands were shown to be glycosylated. Western blot analysis indicated that the three bands are IFN-gamma and lack an intact carboxyl terminus. The circular dichroic (CD) spectra showed that conformation of the CHO-derived IFN-gamma is similar in the native state, in acid, and after renaturation from acid to the E. coli-derived IFN-gamma. These results indicate that neither glycosylation nor carboxy-terminal processing affects conformational properties of the protein, as detected by CD spectroscopy. However, the antiviral activity was fourfold lower for the preparation of CHO-derived IFN-gamma than for the E. coli-derived IFN gamma. A different preparation or a natural IFN-gamma preparation with less extensive carboxy-terminal processing showed similar conformational properties and antiviral activity to the E. coli-derived IFN-gamma. These results indicate that the carboxyl terminus, but not glycosylation, plays an important role in the antiviral activity of IFN-gamma. PMID- 3106527 TI - [Detection of serum Candida antigen by an enzyme-linked immunosorbent assay with avidin-biotin system (2)]. PMID- 3106528 TI - [Meningitis caused by Haemophilus influenzae type Ib resistant to ampicillin and chloramphenicol]. PMID- 3106529 TI - [Diagnosis of enterotoxigenic Escherichia coli by the hydrophobicity test using salting out]. PMID- 3106531 TI - [Fundamental studies on the measurement of antibody against C-polysaccharide extracted from cell walls of group A Streptococcus by the enzyme-linked immunosorbent assay (ELISA)]. PMID- 3106530 TI - [Comparative clinical trial of HBK and amikacin (AMK) in the treatment of respiratory infections]. PMID- 3106532 TI - [Antibiotic susceptibility of Haemophilus influenzae from clinical isolates]. PMID- 3106533 TI - [Detection of antibodies to delta antigen in hepatitis B virus infections]. PMID- 3106534 TI - [Cellular analysis of the bronchoalveolar lavage fluid of hamsters infected with Mycoplasma pneumoniae]. PMID- 3106536 TI - [The 61st congress of the Japanese Association for Infectious Diseases. 2-3 April 1987, Tokyo. Abstracts]. PMID- 3106535 TI - [Antimicrobial susceptibility of Vibrio parahaemolyticus and Vibrio alginolyticus isolated from human feces and foods]. PMID- 3106537 TI - [The effect of thermochemotherapy on ovarian cancer using human ovarian cancer xenograft transplanted to nude mice]. PMID- 3106539 TI - [A case of Lafora disease diagnosed by liver biopsy]. PMID- 3106540 TI - [Pathophysiology and treatment of thrombosis. (5) An attempt at the diagnosis of thrombosis by radio-labeled platelets]. PMID- 3106538 TI - [Changes in Leu 7+ lymphocyte subset in the peripheral blood of cancer patients during radiotherapy--analysis with flow-cytometry]. PMID- 3106541 TI - [Studies on the hypothalamic-pituitary dopaminergic system in Parkinson's disease and spinocerebellar degeneration. Response to TRH and sulpiride]. PMID- 3106542 TI - Dislocation of extensor tendons of the hand caused by focal myoclonic epilepsy. AB - A case of dislocation of the extensor tendons of the hand caused by focal myoclonic epilepsy is presented. This particular aetiology, which has not previously been reported, is discussed. The tendons were repositioned and there was no sign of recurrence one year later. PMID- 3106543 TI - Reproducibility of ventilatory measurements during sleep on different nights in patients with chronic obstructive pulmonary disease. AB - To evaluate the reproducibility of respiratory measurements between nights we performed studies in 20 outpatients with stable, moderately severe chronic obstructive pulmonary disease. All patients had symptoms from their lung disease but had no sleep complaints. Their mean age was 61 years, mean 1-second forced expiratory volume was 42% of predicted, and mean functional residual capacity 195% of predicted. Arterial Pco2 averaged 40 +/- 1 (SEM) mm Hg and mean Po2 64 +/ 1 mm Hg. Sleep was monitored for 7 hours by standard techniques on 2 nights 1 week apart. Breathing was assessed by measuring airflow at the nose and mouth with thermistors, and rib cage and abdominal respiratory movements with inductive plethysmography. Oxygen saturation was measured with an ear oximeter. Patients slept on the average 58% of the time in the first night and 63% in the second. Arousals were common but apneas uncommon in both nights. There was no significant difference in median nocturnal O2 saturation on the 2 nights. Tidal volume and minute ventilation, but not respiratory rate, were significantly lower and more variable in rapid eye movement (REM) sleep as compared with wakefulness and non REM sleep; however, mean values and the variance for tidal volume, respiratory rate, or minute ventilation were similar on both nights. PMID- 3106544 TI - Intracranial extension of paranasal sinus aspergillosis. PMID- 3106545 TI - Malignant external otitis. AB - During the years 1972-1985, 50 patients with malignant external otitis (MEO) were seen in our department. All our patients complained of severe earache; they presented initially with an apparently simple external otitis, but failed to improve when the usual measures were adopted. They all presented with granulation tissue in the external ear canal, and five of our patients had multiple cranial nerve involvement. MEO is in effect a severe external otitis which, if untreated, proceeds towards an osteomyelitis of the skull base. MEO is more prevalent in the summer, when external otitis is rampant. In some years, a relatively large number of these patients appear; in others there are none. The reason for this is unknown. In Israel, the disease is more prevalent in Jews than in Arabs. Diabetes was present in 68 per cent of our patients-severe diabetes in 42 per cent, mild diabetes in 26 per cent but 32 per cent of our patients were diabetes-free. The only otological past history in our patients was of a recent traumatic insult to the external ear canal; this was the case in about 8 per cent of them. Today, the treatment of choice of this important disease is local debridement supplemented by appropriate antibiotic treatment for 6-8 weeks. This should include some semi synthetic penicillin to which pseudomonas aeruginosa is sensitive, combined with an appropriate aminoglycoside. During the earlier years of our encounter with MEO, two of our 10 patients died of it; later on, when we learned better how to treat it, the mortality rate decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106546 TI - Malignant external otitis versus acute external otitis. AB - Malignant External Otitis (MEO) and Acute External Otitis (AEO) are clinically very similar in their beginnings. It is important to differentiate between them very early. Bone scanning is the best diagnostic tool. Eight cases of AEO and MEO are herewith presented. PMID- 3106547 TI - The diagnostic criteria of malignant external otitis. AB - The diagnostic criteria of malignant external otitis (MEO) have been reviewed. They were divided into two categories: obligatory and occasional. The obligatory criteria are: pain, edema, exudate, granulations, microabscess (when operated), positive bone scan or failure of local treatment often more than 1 week, and possibly pseudomonas in culture. The occasional criteria are diabetes, cranial nerve involvement, positive radiograph, debilitating condition and old age. All of the obligatory criteria must be present in order to establish the diagnosis. The presence of occasional criteria alone does not establish it. The importance of Tc99 scan in detecting osteomyelitis is stressed. When bone scan is not available, a trial of 1-3 weeks of local treatment is suggested. Failure to respond to such treatment may assist in making the diagnosis of MEO. PMID- 3106548 TI - Activation of murine polymorphonuclear neutrophils for fungicidal activity by recombinant gamma interferon. AB - Recombinant murine gamma-interferon (IFN) was tested for its ability to enhance murine polymorphonuclear neutrophil (PMN) fungicidal activity in vitro. PMNs, elicited by intraperitoneal injection of thioglycollate 4 hr prior to collection, were treated with 0.00003-300,000 units of IFN per milliliter for 1 hr prior to challenge with yeast form Blastomyces dermatitidis. These PMNs were not fungicidal for Blastomyces in the absence of IFN; significant enhancement of PMN fungicidal activity by IFN treatment occurred in a dose-dependent manner with maximal enhancement observed at 30,000 U/ml (21% killing). Pretreatment of IFN with rabbit anti-IFN antiserum before addition to PMNs eliminated the enhancement of fungicidal activity by effective doses of IFN. PMN fungicidal activity against phagocytizable Candida albicans was significantly (P less than .001) higher (71.3 +/- 17.4%) than against B. dermatitidis. Candidacidal activity was not significantly enhanced by IFN treatment of PMNs. Exogenously added lipopolysaccharide, at levels corresponding to those found in this preparation of IFN, did not activate PMNs for enhanced fungicidal capacity. These data indicate a stimulatory role for IFN in the killing of B. dermatitidis by PMNs, suggesting that IFN is an active component of the communication between T lymphocytes and PMNs with respect to antimicrobial resistance. They suggest a natural role for IFN in host defense against blastomycosis and other fungal infections, and a possible therapeutic use for exogenous IFN in fungal disease. PMID- 3106549 TI - Pantethine inhibits cholesterol and fatty acid syntheses and stimulates carbon dioxide formation in isolated rat hepatocytes. AB - The effects of pantethine on cholesterol and fatty acid metabolism were investigated in isolated rat hepatocytes. Preincubation of the cells with pantethine induced a concentration-dependent decrease of the radioactivity incorporated into carbon dioxide and lipids in incubations with [2-14C]acetate. When pantethine and the labeled substrate were simultaneously added to the cell suspension, there was an enhancement of carbon dioxide radioactivity at short incubation time (5 min) whereas, at longer incubation time, values were comparable to those of controls; lipid radioactivity, instead, was dramatically reduced by pantethine even at short incubation time and decreased further during the incubation, being 23% of that of controls at 60 min. Analysis of the incubation medium showed that pantethine induced a concentration- and time dependent release of acetate into the medium. Results of the effect of the acetate concentration on the incorporation of [2-14C]acetate radioactivity into CO2 and lipids in control hepatocytes allowed the conclusion that the above described modifications induced by pantethine are only partially attributable to the dilution of the labeled substrate, and that catabolism of acetate to carbon dioxide is stimulated by the disulphide pantethine, whereas cholesterol and fatty acid syntheses are inhibited. PMID- 3106550 TI - Primary structure of apolipoprotein A-II from inbred mouse strain BALB/c. AB - The primary structure of apolipoprotein A-II (apoA-II) isolated from the plasma high density lipoprotein (HDL) fraction of the inbred mouse strain BALB/c is described in this work. The complete 78 amino acid protein sequence was determined by proteolytic fragmentation, gas-phase microsequence analysis, and fast atom bombardment (FAB) mass spectrometry. The apolipoprotein has a calculated molecular weight of 8,715 and a net negative charge conveyed by ten acidic and eight basic amino acid residues. There exists a 55% amino acid sequence homology between the BALB/c mouse apoA-II and human apoA-II. Unlike human plasma apoA-II, which exists as a disulfide dimer, BALB/c apoA-II lacks cysteine and is a monomer. BALB/c apoA-II contains one residue each of histidine and arginine, neither of which are found in the human A-II protein. Chou and Fasman analysis of the BALB/c apoA-II primary structure predicts approximately 68% alpha-helical potential compared with a 62% potential for human apoA-II. The alpha-helical domains are structurally amphipathic, generating a polar and an apolar face consistent with the proposed models describing apolipoprotein phospholipid interaction. PMID- 3106551 TI - Fatty acid composition of diacyl, alkylacyl, and alkenylacyl phospholipids of control and arachidonate-depleted rat polymorphonuclear leukocytes. AB - Phospholipid fatty acid composition and phospholipid subclass distribution of control and arachidonate-depleted rat polymorphonuclear leukocytes (PMN) were compared. The 20:4-depleted PMN contained significantly higher amounts of 16:1, 18:1 and 20:3 (delta 5,8,11) and lower amounts of 18:2 and 20:4 than the phospholipids from control cells. Choline-containing glycerophospholipids (CGP) were the major phospholipids of both control and 20:4-depleted cells representing 34% and 37% of the total phospholipids, respectively. Significant amounts of ethanolamine-containing glycerophospholipids (EGP) (29% and 30%) and sphingolipids (20% and 18%) were also present in both cell types. Serine containing glycerophospholipids (SGP) together with inositol-containing glycerophospholipids (IGP) constituted 16% and 13% of the phospholipids in control and 20:4-depleted cells, respectively. CGP from control cells had significantly higher amounts of 16:0 and 18:2 and lower amounts of 18:0 and 20:4 than EGP, whereas CGP from 20:4-depleted cells has higher amounts of 16:0 and 16:1 and lower amounts of 20:3 than EGP. Analysis of the subclass composition of CGP and EGP revealed that both control and 20:4-depleted cells contained significantly large amounts of alkylacyl-GPC and alkenylacyl-GPE. Small amounts of alkylacyl-GPE and alkenylacyl-GPC were also observed. The predominant fatty acyl residues found in the 1,2-diacyl-GPC, alkylacyl-GPC of control cells were 16:0, 18:0, 18:1, 18:2, and 20:4, while those of 20:4-depleted cells were 16:0, 16:1, 18:0, 18:1, and 20:3. More than 60% of CGP-bound 20:4 of control cells and about 70% of the CGP-bound 20:3 of 20:4-depleted cells were found in their alkylacyl species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106552 TI - Justice and competitive markets. AB - This essay challenges the view that the provision of health care must take place within a competitive-free system. The author argues that, presuming that there is a requirement to meet the demands of those who cannot pay for health care, a competitive market provides a good way to deal with injustices within the health care system. The author concludes that the demands for justice are best met when indigent individuals use some portion of the funds they receive from the government to purchase one of the many competing forms of health care. This scheme requires a competitive market in the delivery of health care. PMID- 3106553 TI - A scanning electron microscopic evaluation of four root canal irrigation regimens. PMID- 3106554 TI - Idiotypic self binding of a dominant germline idiotype (T15). Autobody activity is affected by antibody valency. AB - We have previously described (1-3) an IgM antibody that binds to PC, expresses the T15 idiotype, and binds also to itself or T15 if insolubilized. Because of the simultaneous presence of complementary idiotopes and paratopes this type of antibody has been termed autobody. The self binding involves the antigen-binding site because the F(ab')2 fragment of T15, PC, and no other haptens inhibit the self binding. DNA sequence analysis of 11E7-1 using primer extension cDNA sequencing showed that the variable sequences of H and L chains of 11E7-1 are identical to the germline sequence of the prototype T15 idiotype. Furthermore, monomeric and dimeric T15 IgA were shown to bind to insolubilized T15 and other T15+ antibodies including 11E7-1. Thus, the self-binding activity is an inherent property of the T15 germline sequence. The self binding is highly dependent on the polymeric state of the binding antibody since the IgM pentamer of 11E7-1 is about three fold more effective than the T15 dimer and 50 times more than the T15 monomer. These data suggest that the self-binding activity of a germline-encoded idiotype may play an important role in the biology of its expression, and more specifically, may be responsible for the establishment of its dominant expression. PMID- 3106555 TI - Gonococcal pilin variants in experimental gonorrhea. AB - When pilus+ Gc were introduced into a male subject's urethra, they gave rise to pilus+ variants whose pilin mRNAs differed from that of input Gc. The differences stemmed from the Gc genome's single complete pilin gene having undergone gene conversion by different partial pilin genes' sequences and by different length stretches of a single partial pilin gene. In some instances, the variant's pilin mRNA appeared to reflect two independent gene-conversion events that used sequences from two different partial pilin genes. The resulting variants' pilins exhibited antigenic differences compared with the pilin polypeptide of input Gc; these differences were discernible by immunoblotting with mAbs. Amino acid and antigenic changes occurred in a segment of the variants' pilin polypeptides that previously was thought to be conserved or constant in sequence. PMID- 3106556 TI - A major immunogen in Schistosoma mansoni infections is homologous to the heat shock protein Hsp70. AB - A 70,000 mol wt protein of Schistosoma mansoni was shown to be a major immunogen that invariably elicited an antibody response in infected humans. The universality of the response to this abundant antigen was confirmed in experimental animals and included the antibody response associated with the protective irradiated cercarial vaccine. We identified the 70,000 mol wt antigen as an S. mansoni homologue of the major eukaryotic heat-shock protein hsp70 by DNA sequence analysis of a cDNA insert from a lambda gt11 clone expressing the antigen and located the immunodominant epitope near the COOH-terminus of the molecule. The antigenic relationship of hsp70 to schistosome infections suggested an important role for this protein in parasite development and pathogenesis. PMID- 3106557 TI - Functional gamma chain-associated T cell receptors on cerebrospinal fluid-derived natural killer-like T cell clones. AB - We have derived 33 independent T cell clones from the cerebrospinal fluid (CSF) of a patient with subacute sclerosing panencephalitis using a single T cell cloning method. 6% (2 of 33) of these clones express the T cell receptor gamma (TCR-gamma) protein and are called CSF TCR-gamma clones. Phenotypic analyses of the CSF TCR-gamma clones indicate that they are WT-31-, CD3+, CD4-, and CD8-. The TCR-gamma protein exists on the cell surface as part of an 85-kD disulphide linked dimer noncovalently associated with the CD3 polypeptides. The CSF TCR gamma clones have NK-like activity that can be inhibited by anti-CD3 mAbs. Both CSF TCR-gamma clones proliferated in response to anti-CD3 mAbs coupled to Sepharose beads and/or IL-2. Furthermore, stimulation of one of these clones with anti-CD3 mAbs results in a rapid rise in intracellular calcium. These data suggest that T cells bearing the CD3-TCR-gamma protein complex are functional and play a role in the human immune response. PMID- 3106558 TI - Variability of L-thyroxine replacement dose in elderly patients with primary hypothyroidism. AB - Sixty-three elderly patients (aged more than 65 years) who manifested primary hypothyroidism during 4 1/2 years from September 1980 to March 1985 were studied. Patients were divided into two groups depending on the presence or absence of chronic associated disorder at the time of diagnosis. Patients in the sick group were required to consume several medications throughout the study period in addition to L-thyroxine for their total therapeutic management. Subjects in the healthy group required L-thyroxine administration alone for their therapy. Prior to institution of L-thyroxine therapy, serum thyroxine (T4) was not significantly different in the two groups. However, serum triiodothyronine (T3) and thyroid stimulating hormone (TSH) levels were significantly lower and T3 resin uptake was significantly higher in the sick group compared with the healthy patients (P less than .01 for all comparisons). Furthermore, these differences in T3, TSH concentration, and T3 resin uptake values appeared to persist on achieving euthyroid state. The optimal daily L-thyroxine dose was markedly lower (97 +/- 3 micrograms) in the sick patients compared with the healthy group (144 +/- 3 micrograms) as well as with the younger counterparts reported in the literature (150 +/- 8 micrograms). These findings indicate that the decrease in optimal daily L-thyroxine dosage reported in previous studies is not a universal finding in all elderly hypothyroid patients; the decrease is present only in patients with associated chronic disorders, and hence may be attributed to the presence of an associated chronic disorder or medications consumed for treatment of these disorders rather than old age. PMID- 3106559 TI - Effects of changes in pulmonary arterial blood flow on ventilation in dogs. PMID- 3106561 TI - [The assessment of pleural biopsy culture in the diagnosis of tuberculous pleurisy]. PMID- 3106560 TI - Hypothalamic-pituitary function in Chinese and idiopathic hypothalamo-pituitary dwarfism. PMID- 3106562 TI - The corrosive effect of root canal irrigants on endodontic instruments. PMID- 3106563 TI - Phosphate depletion and ATP metabolism in muscle and liver during trauma, sepsis and total parenteral nutrition. PMID- 3106564 TI - Murine T cell clones directed to rabies virus: isolation and some of their properties. AB - Seventeen Thy-1+ cell clones were induced in A/J mice immunized with the HEP Flury strain of rabies virus after repeated stimulations with antigens in vitro. Ten clones with cell surface phenotypes Thy-1+, Lyt-1-,2+ were cytotoxic T lymphocytes (CTL) which lysed the virus-infected target cells under H-2 restriction. Target cells expressed the G and M2 structural proteins of rabies virus on their surface; however, target lysis by CTL clones was not blocked by anti-rabies antibody or by monoclonal antibodies to these proteins. All of the CTL clones efficiently and equally lysed target cells infected with three different strains of rabies virus and were cross-reactive for target cells infected with one (Duvenhage virus) of three different rabies serogroup viruses. Another five clones having phenotype Thy-1+, Lyt-1+,2- did not show any cytotoxic activity. The proliferation response of these clones to antigen stimulation was virus-specific and H-2-restricted. These clones were able to grow in culture medium without any or with the addition of low concentrations of T cell growth factor, in contrast to CTL clones, and were considered to be helper T lymphocytes (HTL). Both CTL and HTL clones produced gamma-interferon in response to antigen stimulation. The remaining two clones were Thy-1+, Lyt-1-,2-, asialo-GM1+, and were not cytotoxic to target cells even in the presence of anti-rabies antibody but were cytotoxic to YAC-1 cells. Further studies with these clones should allow us to investigate more closely the role of T cells in the pathogenesis of rabies. PMID- 3106565 TI - Four serotypes of haemorrhagic fever with renal syndrome viruses identified by polyclonal and monoclonal antibodies. AB - Antigenic relationships among 20 strains of haemorrhagic fever with renal syndrome (HFRS) viruses isolated in Korea, China, U.S.S.R., Finland, Japan and U.S.A. were examined with rat immune sera, patient sera, eight monoclonal antibodies against the SR-11 strain and 10 monoclonal antibodies against the 76 118 strain. Antigen analyses by indirect immunofluorescent antibody and immune adherence haemagglutination tests using polyclonal and monoclonal antibodies demonstrated that HRFS viruses may be divided into four serotypes, i.e. Apodemus (Type 1), Rattus (Type 2), Clethrionomys (Type 3) and Microtus (Type 4). Further, it was demonstrated that Type 1 could be divided into three subtypes and Type 3 into two subtypes. The two sets of monoclonal antibodies were useful for identification of the antigenic types of viruses isolated from patients in endemic areas. PMID- 3106566 TI - Characterization of scrapie infection in mouse neuroblastoma cells. AB - A mouse neuroblastoma cell line was successfully infected with scrapie agent. Agent derived from infected mouse brain or spleen infected cultures. However, agent from infected hamsters did not infect mouse cell cultures, suggesting that species specificity influenced the infection process in vitro. Positive cultures supported scrapie replication for as many as 47 passages in vitro. Agent was shown to be cell-associated and between 631 and 7943 unselected culture cells constituted 1 mouse LD50. However, fluctuation analysis indicated that only one of 144 cells in unselected cultures was actually infected. Thus, agent was confined to a small percentage of cells and only 4.4 to 55.1 positive cells were needed to confer a mouse LD50. PMID- 3106567 TI - A genetic analysis of glutamatergic function in Drosophila. AB - Neurotransmitters are essential for communication between neurons and hence are vital in the overall integrative functioning of the nervous system. Previous work on acetylcholine metabolism in the fruit fly, Drosophila melanogaster, has also raised the possibility that transmitter metabolism may play a prominent role in either the achievement or maintenance of the normal structure of the central nervous system in this species. Unfortunately, acetylcholine is rather poorly characterized as a neurotransmitter in Drosophila; consequently, we have begun an analysis of the role of glutamate (probably the best characterized transmitter in this organism) in the formation and/or maintenance of nervous system structure. We present here the results of a series of preliminary analyses. To suggest where glutamatergic function may be localized, an examination of the spatial distribution of high affinity [3H]-glutamate binding sites are presented. We present the results of an analysis of the spatial and temporal distribution of enzymatic activities thought to be important in the regulation of transmitter glutamate pools (i.e., glutamate oxaloacetic transaminase, glutaminase, and glutamate dehydrogenase). To begin to examine whether mutations in any of these functions are capable of affecting glutamatergic activity, we present the results of an initial genetic analysis of one enzymatic function, glutamate oxaloacetic transaminase (GOT), chosen because of its differential distribution within the adult central nervous system and musculature. PMID- 3106568 TI - Posttranslational modification of neurofilament polypeptides in rabbit retina. AB - Three polypeptides that compose neurofilaments, designated H, M, and L, are synthesized in the cell bodies of neurons and subsequently conveyed down their axons by the process of slow axonal transport. The axonal form of H, which is a component of the cross bridges between the neurofilaments, is antigenically different from the form in the cell bodies and dendrites. To understand how this special form of H is directed to the axon, and more generally how intracellular differentiation is established and maintained by the selective delivery of different molecular species to different compartments of a cell, we have studied the events that occur immediately after the synthesis of the three neurofilament polypeptides in the retinas of rabbits. We observed that H and M are synthesized in the retina as precursor polypeptides, EH and EM, that migrate markedly faster on SDS polyacrylamide gels than their mature axonal forms. The maturation of these precursors requires more than one day and appears to involve their phosphorylation. Only the electrophoretically mature forms appear in the axons of the retinal ganglion cells in the optic nerve. We consider the following interpretation of these observations. Shortly after they are translated in the cell body, the neurofilament polypeptides become phosphorylated at multiple sites. However, only after they have moved a distance of several hundred micrometers down the axon, H and M are phosphorylated at additional sites, causing their conformation or binding properties to change. This change, which is reflected in the reduction of their electrophoretic mobility and the appearance of new antigenic determinants, may function to alter the H-mediated crossbridges and produces the morphological and structural properties of the neurofilament lattice that is characteristic of axons. PMID- 3106569 TI - Resection of heterotopic ossification and Didronel therapy--regaining wheelchair independence in the spinal cord injured patient. AB - Ankylosis of the joints secondary to heterotopic ossification in the spinal cord injured is not uncommon. Five patients had ankylosis of the hip and knee joints which limited their ability to function in their wheelchairs. They underwent eight resections to improve their functional capabilities. All patients were treated pre- and postoperatively with disodium etidronate (EHDP, DIDRONEL). The average interval from injury to surgery was nine years nine months and the average interval from surgery to follow-up was two years three months. With clearly defined goals, proper patient selection, good pre- and postoperative management and intense rehabilitation combined with Didronel, optimum functional results were achieved. PMID- 3106570 TI - The reaction between ferrous polyaminocarboxylate complexes and hydrogen peroxide: an investigation of the reaction intermediates by stopped flow spectrophotometry. AB - The reactions of Fe(II)EDTA, Fe(II)DTPA, and Fe(II)HEDTA with hydrogen peroxide near neutral pH have been investigated. All these reactions have been assumed to proceed through an active intermediate, I1, (Formula: see text) where pac is one of the three polyaminocarboxylates mentioned above. I1, whether .OH radical or an iron complex, reacts with ethanol, formate, and other scavengers at rates relative to k2 that, with the exception of t-butanol and benzoate, are similar, but not identical, to those expected for the.OH radical. In contrast, at pH 3, in the absence of ligands the reaction of I1 with Fe2+ was inhibited by ethanol and t-butanol and the reactivity of I1 towards these two scavengers relative to ferrous ion is identical to that exhibited by the hydroxyl radical. When pac = HEDTA, the intermediate of the first reaction reacts with formate ion to form the ferrous HEDTA ligand radical complex, which is characterized by absorption maxima at 295 nm (epsilon = 2,640 M-1 cm-1) and 420 nm (epsilon = 620 M-1 cm-1). For the reaction of Fe(II)HEDTA with H2O2, the following mechanism is proposed: (Formula: see text) where k17 = 4.2 X 10(4) M-1 sec-1 and k19 = 5 +/- 0.2 sec-1. PMID- 3106571 TI - Evidence for an involvement of membrane lipids in the control of neuronal nicotinic receptor function using bungarotoxin II-S1. AB - Previous work has shown that a toxin fraction, bungarotoxin (BGT) II-S1, isolated from Bungarus multicinctus venom could inhibit nicotinic receptor-mediated function. Experimental evidence suggested that this effect of the toxin might be due to a direct interaction of the toxin at the acetylcholine binding site and/or to its phospholipase activity. The toxin's enzymic activity has been further characterized; it has phospholipase activity of the A2 type with a Vmax of 12 pmol/min/ng protein and a Km of 300 microM. Phospholipases can produce their effects on a tissue through a variety of mechanisms including the disruption of important lipid protein bonds or the production of free fatty acids which interact with the tissue. To test for this latter possibility, various concentrations of fatty acid-free bovine serum albumin were added to the incubation medium. Fatty acid-free bovine serum albumin partially reversed the inhibition of carbachol-stimulated 1-[1,2-3H(N)]amino-4-guanidobutane ([3H]agmatine) uptake (used as a measure of ion flux) into the ganglion produced by BGT II-S1 (1.0 microM). In an attempt to determine which fatty acids might be responsible for this effect, various fatty acids were added to the incubation medium and their effect on nicotinic receptor-mediated [3H]agmatine uptake determined. Arachidonic acid decreased amine uptake by approximately 50% over the control carbachol-stimulated uptake; linoleic and oleic acid, on the other hand, did not significantly affect the response. This observation could imply that arachidonic acid is the fatty acid produced by the action of BGT II-S1 on the tissue to mediate the toxin's inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106572 TI - Effect of bicuculline-induced status epilepticus on prostaglandins and hydroxyeicosatetraenoic acids in rat brain subcellular fractions. AB - Rat cerebrum, prelabeled in vivo by intraventricular injection of [1 14C]arachidonic acid, was used to assess cyclooxygenase and lipoxygenase reaction products in total homogenates, cytosol, synaptosomes, and microsomes. Effects of bicuculline-induced status epilepticus on arachidonic acid metabolism in synaptosomes and microsomes were also measured. Lipoxygenase activity, resulting in the synthesis of hydroxyeicosatetraenoic acids (HETEs), and cyclooxygenase activity, resulting in the synthesis of prostaglandins (PGs), were measured by reverse-phase and normal-phase HPLC with flow scintillation detection. Endogenous lipoxygenase products in synaptosomes were identified by capillary gas chromatography-mass spectrometry. PGs and HETEs were detected in all subcellular fractions. The synaptosomal fraction showed the highest lipoxygenase activity, with 5-HETE, 12-HETE, and leukotriene B4 as the major products. Following bicuculline-induced status epilepticus, endogenous free arachidonic acid and other fatty acids accumulated in synaptosomes, but not in microsomes. Incorporation of [1-14C]arachidonic acid into synaptosomal and microsomal phospholipids was decreased after bicuculline treatment. Bicuculline-induced status epilepticus resulted in increased synthesis of HETEs in synaptosomes. PG synthesis increased in the microsomal fraction. When [1-14C]arachidonic acid labeled synaptosomes and microsomes were incubated for 1 h at 37 degrees C the synthesis of eicosanoids, particularly PGD2, was increased significantly in bicuculline-treated rats, as compared with untreated rats. Depolarization (45 mM K+) of synaptosomes induced a loss of [1-14C]arachidonic acid from phosphatidylinositol, and increased the synthesis of PGD2 and HETEs, an effect that was enhanced in bicuculline-treated rats. This study localizes changes in arachidonic acid metabolism and lipoxygenase activity resulting from bicuculline induced status epilepticus in the brain subcellular fraction enriched in nerve endings. PMID- 3106573 TI - Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4 phenylpyridinium ion on activities of the enzymes in the electron transport system in mouse brain. AB - The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4 phenylpyridinium ion (MPP+) on activities of enzyme complexes in the electron transport system were studied using isolated mitochondrial preparations from C57BL/6J mouse brains. Both MPTP and MPP+ dose-dependently inhibited activity of NADH-ubiquinone oxidoreductase (EC 1.6.5.3). The inhibition was reversible. Preincubation of freeze-thawed mitochondria with MPTP or MPP+ had no effect on the inhibition; however, when nonfrozen mitochondria were used, NADH-ubiquinone oxidoreductase activity was reduced to 46% of that in the nonincubated sample after a 5-min preincubation with MPTP and to 77% of that in the nonincubated sample after a 5-min preincubation with MPP+. Kinetic analyses revealed that inhibition of MPTP was noncompetitive and that of MPP+ uncompetitive with respect to NADH. On the other hand, inhibition of MPTP was uncompetitive and that of MPP+ noncompetitive with respect to ubiquinone. Succinate-ubiquinone oxidoreductase (complex II), dihydroubiquinone-cytochrome c oxidoreductase (complex III), and ferrocytochrome c-oxygen oxidoreductase (EC 1.9.3.1) activities were either slightly inhibited or not inhibited by MPTP or MPP+. The significance of these findings is discussed in relation to the mechanism of MPTP-induced neuronal degeneration. PMID- 3106574 TI - Specific antisera against the catecholamines: L-3,4-dihydroxyphenylalanine, dopamine, noradrenaline, and octopamine tested by an enzyme-linked immunosorbent assay. AB - Antisera were raised against L-3,4-dihydroxyphenylalanine (L-DOPA), dopamine (DA), noradrenaline (NA), and octopamine (OA). This was achieved by coupling each molecule to bovine serum albumin or human serum albumin using glutaraldehyde. The conjugated aromatic amines were kept in a reducing medium containing sodium metabisulfite. Antiserum specificity was tested using an enzyme-linked immunosorbent assay method for catecholamines. Competition experiments were done between the immunogen coated on the well plates and each catecholamine, either in the free state or in conjugated form, previously incubated with an antiserum. In each case, the nonconjugated compound was poorly recognized. The nonreduced conjugates of L-DOPA and DA were well recognized, whereas those of NA and OA were poorly immunoreactive. The cross-reactivity ratios established in the competition experiments allowed the specificity of the immune response to be defined. In each case, it was found to be high. The results suggest that the antibodies of L-DOPA and DA antisera recognize preferentially the catechol moiety, whereas for the anti-NA and anti-OA antibodies, the lateral chain is important. PMID- 3106575 TI - Threonine entry into rat brain after diet-induced changes in plasma amino acids. AB - Passage of amino acids across the blood-brain barrier is modified by the amino acid composition of the blood. Because blood amino acid concentrations respond to changes in protein intake, we have examined associations among diet, plasma amino acid patterns, and the rate of entry of threonine into the brain. Rats were adapted for 8 h/day for 7-10 days to diets containing 6, 18, or 50% casein before receiving a single, independently varied, final meal of a diet containing 0, 6, 18, or 50% casein. After 4-7 h, they were anesthetized and infused intravenously with [14C]threonine for 5 min before plasma and brain samples were taken for determination of radioactivity and amino acid content. Plasma and brain threonine concentrations decreased as protein content increased in the diets to which the rats had been adapted. Plasma threonine concentrations increased twofold, from 1.6 to 3.0 mM, when rats adapted to 6% casein meals received a single 50% casein meal rather than a nonprotein meal; a fivefold increase, from 0.13 to 0.69 mM, occurred when rats had been previously adapted to 50% casein meals. Increasing the protein content of the final meal did not increase brain threonine concentrations. Highest and lowest rates of threonine entry into the brain occurred, respectively, in rats adapted to 6 and 50% casein meals. Changes in plasma threonine concentrations and threonine flux into brain reflected protein content of both pretreatment and final meals. PMID- 3106576 TI - Evidence for the participation of a cytosolic NADP+-dependent oxidoreductase in the catabolism of gamma-hydroxybutyrate in vivo. AB - The concentration of gamma-hydroxybutyrate (GHB) in brain, kidney, and muscle as well as the clearance of [1-14C]GHB in plasma have been found to be altered by the administration of a number of metabolic intermediates and drugs that inhibit the NADP+-dependent oxidoreductase, "GHB dehydrogenase," an enzyme that catalyzes the oxidation of GHB to succinic semialdehyde. Administration of valproate, salicylate, and phenylacetate, all inhibitors of GHB dehydrogenase, significantly increased the concentration of GHB in brain; salicylate increased GHB concentration in kidney, and alpha-ketoisocaproate increased GHB levels in kidney and muscle. The half-life of [1-14C]GHB in plasma was decreased by D-glucuronate, a compound that stimulates the oxidation of GHB by this enzyme and was increased by a competitive substrate of the enzyme, L-gulonate. The results of these experiments suggest a role for GHB dehydrogenase in the regulation of tissue levels of endogenous GHB. PMID- 3106577 TI - Factor VIII R:Ag as a prognostic parameter in intracranial haemorrhage. AB - Factor VIII R:Ag was measured serially in 42 patients who had intracranial haemorrhage. It was found that the factor decreased or remained static in the 24 patients who improved (p less than 0.025), while it increased in the 18 who died (p less than 0.0005). It is suggested that this factor can be used as a prognostic parameter to predict the outcome after intracranial haemorrhage. PMID- 3106579 TI - Cerebellar syndrome in lithium poisoning: a case of partial recovery. PMID- 3106578 TI - Focal epileptic activity following intravenous contrast material injection in patients with metastatic brain disease. AB - Four patients with metastatic brain disease were referred for computed tomographic (CT) examination with contrast material injection. Within 2 to 4 minutes after the intravenous administration of water soluble contrast agent, focal epileptic activity occurred. The seizures became generalised in two of the patients who later died following status epilepticus. In the other two patients the focal seizures correlated with the localisation of the metastatic mass lesions. None of the patients had a previous history of epilepsy. PMID- 3106580 TI - A case of tabes dorsalis with tonic pupils and lightning pains relieved by sodium valproate. PMID- 3106582 TI - ELISA using mycobacterial antigens as a diagnostic aid for tuberculous meningitis. AB - An enzyme-linked immunosorbent assay (ELISA) was studied as a possible laboratory test to aid in the diagnosis of tuberculous meningitis (TBM) in an Indian population. The assay detected mycobacterial antibodies in the cerebrospinal fluid (CSF) of TBM patients. Three antigens, PPD, BCG and M. tuberculosis were tested for use in the assay and of these, M. tuberculosis was found to be the most suited. A sensitivity of 72% and specificity of 92% with M. tuberculosis as antigen was obtained for the ELISA under discussion. The system therefore does hold promise as a diagnostic laboratory test for TBM. PMID- 3106581 TI - A mitochondrial encephalomyopathy with cardiomyopathy. A case revealing a defect of complex I in the respiratory chain. AB - We describe a 16-year-old Japanese girl with a mitochondrial encephalomyopathy who presented with progressive dementia, limb weakness and atrophy, episodic vomiting, generalized convulsions, myoclonic seizures, and hypertrophic cardiomyopathy. CT scan revealed transient focal low density areas in her occipital and parietal lobes, and cerebellar atrophy. The clinical features were consistent with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Microscopically, most of muscle fibers in the skeletal muscles and heart were occupied by markedly increased mitochondria. Polarographic studies on mitochondria isolated from postmortem heart muscle showed severe impairment of oxidation of NADH-linked substrates in contrast to normal succinate oxidation. The rotenone-sensitive NADH-coenzyme Q reductase activity was markedly decreased in heart, skeletal muscle and liver mitochondria. The biochemical investigations have led to the identification of a defect of complex I in the respiratory chain. Reported cases of a defect of complex I have revealed pure myopathy, encephalopathy or encephalomyopathy. The reason for a varied clinical expression of a single defect remains to be clarified. PMID- 3106583 TI - Clinical course of breast cancer patients with liver metastases. AB - Between June 1973 and November 1980, 1,171 patients with metastatic breast cancer were treated with various doxorubicin-containing regimens at our institution (M.D. Anderson Hospital and Tumor Institute, Houston). Retrospective analysis of all 233 cases (20%) with liver metastases was done to correlate various clinical and biochemical characteristics with response to treatment, survival, and causes of death. A similar analysis was performed for 58 consecutive patients with liver metastases treated at this hospital between December 1955 and December 1957 with hormone therapy or single-agent chemotherapy. Objective responses were observed in 132 of 233 patients (57%) treated with combination chemotherapy. The median survival was 14 months in the 1970s and 5 months in the 1950s. Among patients who had liver metastases at the time of initial diagnosis of breast cancer, survival was longer for the group treated with combination chemotherapy. All cases were classified according to the number of organ sites involved by metastases. Patients with only liver metastases, or liver plus bone lesions had the longest survival. Other clinical and biochemical factors that correlated significantly with longer survival were: no prior chemotherapy, performance status of 1 to 2, absence of ascites, normal bilirubin and lactic dehydrogenase (LDH), SGOT less than or equal to 2 times normal and albumin greater than 4.5 g/dL. The main cause of death was multiorgan failure, with only 20% of patients dying of liver failure. The present study shows that the presence of liver metastases in breast cancer is not by itself an ominous factor. Most patients respond to therapy, and significant palliation with extended survival is possible for several prognostic subgroups. Further improvement in length and quality of survival is expected with earlier diagnosis. PMID- 3106584 TI - A phase I clinical trial of recombinant DNA gamma interferon. AB - Recombinant gamma interferon (r-GIFN) demonstrates in vitro and in vivo characteristics that contrast with those of alpha and beta interferons. It has relatively weak antiviral properties, yet relatively potent immunomodulatory effects. A phase I trial was performed with r-GIFN (specific activity 2.6 X 10(6) IU/mg protein), administered as a continuous intravenous (IV) infusion over 24 hours for five days (Cl X 5) and repeated every 28 days. This schedule was chosen based on the short half-life of r-GIFN in animal systems and the in vitro augmentation of biologic effects with continuous exposure to interferons. Twenty one patients with refractory solid tumors received 46 evaluable courses of therapy. The dose-limiting toxicities included fever, flu-like symptoms, cardiovascular toxicity, and neurotoxicity. The cardiovascular toxicity included hypotension and one episode of cardiac ischemia with chest pain. Neurotoxicity consisted of lethargy and confusion. These toxicities were reversible, and although dose-limiting, occurred sporadically throughout all dosage levels. Mild to moderately severe non-dose-limiting toxicities included nausea and vomiting, leukopenia, and liver function abnormalities. Other infrequent toxicities included hypocalcemia, diarrhea, constipation, and alopecia. The maximally tolerated dose of r-GIFN on this schedule is 0.5 X 10(6) IU/m2/d. Partial responses were seen in one patient with metastatic melanoma and in one patient with renal cell carcinoma. Toxicity and antitumor activity were seen at doses where interferon serum levels could not be detected by radioimmunoassay. In addition, the toxicity and antitumor activity seen were at much lower doses than previously described for shorter infusion schedules of other recombinant gamma interferon preparations. Differences in biologic activity of interferon preparations and/or differences in scheduling may account for this variability. Although this study defines a recommended phase II dose of r-GIFN based on the maximally tolerated dose, the optimal therapeutic index may exist at a lower dosage level. PMID- 3106585 TI - The efficacy of mesna (2-mercaptoethane sodium sulfonate) as a uroprotectant in patients with hemorrhagic cystitis receiving further oxazaphosphorine chemotherapy. AB - We examined the possibility of continuing oxazaphosphorine therapy in patients with previously documented cyclophosphamide- or ifosfamide-induced hematuria by concomitant use of the uroprotective agent, mesna. Twenty-six patients with oxazaphosphorine-induced hematuria received additional cyclophosphamide or ifosfamide with mesna. Twelve, who had previously experienced hematuria with ifosfamide, received a median of 3.5 more cycles of ifosfamide/mesna. One patient developed further hematuria (grade 1). Of seven patients who experienced acute hematuria with cyclophosphamide, one experienced further hematuria after an additional course of cyclophosphamide with mesna, but none of the other six patients developed further hematuria when administered either cyclophosphamide/mesna (two) or ifosfamide/mesna (four). Seven patients who had chronic cyclophosphamide-induced hematuria had further oxazaphosphorine with mesna without worsening of their hematuria. Mesna is an effective uroprotective agent that prevents recurrent acute hemorrhagic cystitis, or worsening of chronic hemorrhagic cystitis, in patients receiving further oxazaphosphorine after previous ifosfamide- or cyclophosphamide-induced hematuria. PMID- 3106586 TI - Changes in local cerebral glucose utilization induced by the beta-carbolines FG 7142 and DMCM reveal brain structures involved in the control of anxiety and seizure activity. AB - The brain regions that may be functionally involved in the control of anxiety and the development of seizures were examined using quantitative 1-14C-deoxyglucose autoradiography. For this purpose, beta-carbolines FG 7142 and DMCM were employed. They exert their effects via the benzodiazepine receptor, and whereas both possess anxiogenic properties, FG 7142 is a proconvulsant and DMCM a potent convulsant. The pattern of increases of local cerebral glucose utilization (LCGU) induced by FG 7142 was mainly restricted to limbic structures, such as the lateral septal nucleus, the anterior thalamic nuclei, and the mamillary nuclei. However, structures involved in motor regulation were also affected. A pronounced increase in LCGU was observed in the posterior part of the substantia nigra, pars reticulata. Further, the LCGU of the globus pallidus, the ventral thalamic nucleus, and the cerebellum was increased. DMCM likewise increased LCGU of the mamillary body and the lateral septal nucleus. In contrast to FG 7142, the hippocampal formation displayed an increase in LCGU, while LCGU of the anterior thalamic nuclei was unchanged. A pronounced increase in LCGU was seen in the substantia nigra, pars reticulata in addition to other structures functionally involved in central motor regulation. The specific benzodiazepine antagonist Ro 15-1788 antagonized the effects of both FG 7142 and DMCM. It is concluded that the beta-carbolines FG 7142 and DMCM produce selective effects upon LCGU that are mediated by benzodiazepine receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106587 TI - Background and bleaching equivalence in steady-state adaptation of vertebrate rods. AB - We have investigated background and bleaching adaptation in vertebrate rods by intracellular recording in the retina of Bufo marinus. Backgrounds and bleaching produce adaptation in photoreceptors and lead to a shift and a compression of the response operating range. Threshold elevation due to backgrounds follows the Rose DeVries rule at low intensities and the Weber-Fechner rule at high intensities. Threshold elevation due to bleaching is linear almost up to 17% bleached pigment and exponential thereafter. An equivalence can be established between bleaching and backgrounds with respect to threshold elevation, on the one hand, and with respect to response compression, on the other. These equivalences are the same within experimental error. The equivalence, moreover, appears to extend to the complete response curve. These results have implications for psychophysics as well as for photoreceptor transduction. PMID- 3106588 TI - Quantitative changes in the synaptic vesicle proteins synapsin I and p38 and the astrocyte-specific protein glial fibrillary acidic protein are associated with chemical-induced injury to the rat central nervous system. AB - Measurements of neuron-specific and glia-specific proteins were used to characterize chemical-induced injury to the rat CNS. Trimethyltin (TMT), a neurotoxicant that preferentially damages neurons in limbic structures, was employed to produce consistent, time-dependent, dose-related, cell type-specific alterations in CNS morphology. Brain weights and histology were used to verify the cytopathological effects of TMT. Accompanying changes in 2 synaptic vesicle associated proteins, synapsin I and p38, and the astrocyte-associated protein, glial fibrillary acidic protein (GFAP), were measured by radioimmunoassay (RIA). Immunohistochemistry of GFAP and incorporation of 3H-thymidine into GFAP-positive astrocytes also were used to characterize astrocytic responses to TMT-induced injury. Finally, quantitative 2-dimensional PAGE was employed to detect additional proteins affected by TMT. Acute administration of TMT caused large dose- and time-dependent decreases in synapsin I and p38 in hippocampus; the same proteins were largely unaffected in a nonlimbic structure, the frontal cortex. Twelve weeks after dosing, the concentrations of synapsin I and p38 and, to a lesser extent, the absolute amount of these proteins in hippocampus had returned to near control values, findings that are suggestive of reactive synaptogenesis. TMT caused large dose- and time-dependent increases in GFAP that were not confined to hippocampus. Twelve weeks after dosing, the amounts of GFAP in hippocampus and frontal cortex had returned to near control values, findings indicative of a transient astrocytic response to brain injury. Immunohistochemistry of GFAP revealed widespread astrocytic reactivity as a consequence of exposure to TMT, a response that resulted in part from the proliferation of astrocytes. Additional neurotypic proteins altered by TMT induced injury included one of the neurofilament (NF) triplet proteins (p68) and a protein with the electrophoretic characteristics of neuron-specific enolase (NSE). The data indicate that measurements of neurotypic and gliotypic proteins may be used to characterize the temporal and regional patterns of neuronal and glial responses to injury. PMID- 3106589 TI - Synapsin I in PC12 cells. I. Characterization of the phosphoprotein and effect of chronic NGF treatment. AB - PC12 cells contain a synapsin I-like molecule. Several serum and monoclonal antibodies raised against bovine brain synapsin I bind to and precipitate this molecule, demonstrating immunochemical similarity between the brain and PC12 species. PC12 synapsin I, like brain synapsin I, is a phosphoprotein: It is phosphorylated in intact cells and, when partially purified, serves as a substrate for several synapsin I kinases. PC12 cell synapsin I is structurally similar to brain synapsin I as shown by peptide mapping of 35S-methionine-and 32P phosphate-labeled molecules from the 2 sources. Chronic NGF treatment of the cells induces a significant increase in the amount of synapsin I relative to total cell protein, measured either by immunolabeling or incorporation of 35S methionine. The synapsin I present in untreated PC12 cells migrates predominantly as a singlet and that present in cells treated chronically with NGF as a doublet in SDS-PAGE. PMID- 3106590 TI - Immunohistochemical localization of choline acetyltransferase during development and in Chats mutants of Drosophila melanogaster. AB - The distribution of choline acetyltransferase (CAT) in the nervous system of Drosophila melanogaster was determined by indirect immunohistochemical procedures using a monoclonal antibody specific to the enzyme. Immunoreactivity was first detected in the nervous system of 16 hr embryos, and increased considerably by the end of embryogenesis. Neuropil was preferentially stained, though cell bodies could also be observed. Staining was prominent in the CNS of all 3 larval instars but decreased substantially during the mid-pupal stage. Prior to eclosion, the level of immunoreactivity increased and the adult staining pattern became discernible. In the adult brain, staining was extensive, with numerous structures, such as the optic lobes and mushroom bodies, staining strongly. The adult thoracic ganglia were also moderately immunoreactive. These results imply a wide distribution of cholinergic neurons in the CNS of Drosophila. Immunoreactivity was also determined for 2 temperature-sensitive CAT mutants, Chats1 and Chats2. These files exhibit reduced CAT activity at permissive temperature, 18 degrees C, which eventually falls to undetectable levels after incubation at nonpermissive temperature, 30 degrees C. Chats2 mutants, after incubation at either 18 or 30 degrees C displayed virtually no staining. This result indicated that the immunoreactivity observed in wild-type flies was specifically associated with the enzyme encoded by the Cha gene. The intensity of staining in Chats1 mutants incubated at 18 degrees C appeared greater than in control flies, even though CAT enzyme activity in Chats1 is lower. This suggests that the enzyme molecule itself is structurally altered in Chats1 mutants. After incubation at 30 degrees C, staining in Chats1 flies decreased but did not disappear. PMID- 3106591 TI - Phosphorylation of neurofilament proteins and chromatolysis following transection of rat sciatic nerve. AB - States of phosphorylation of neurofilament proteins were examined in the perikarya of rat sensory and motor neurons between 3 and 28 d following either a distal transection [6-7 cm from the L4-L5 dorsal root ganglia (DRG)] or a proximal transection (1-2 cm from the L4-L5 DRG) of the sciatic nerve. Paraffin sections of the right (experimental) and left (control) L4 and L5 DRG from animals with unilateral transection of the right distal sciatic nerve were stained immunocytochemically with monoclonal antibodies to phosphorylation dependent (NF-P), dephosphorylation-dependent (NF-dP), or phosphorylation independent (NF-ind) epitopes on the largest (NF200), mid-sized (NF150), or smallest (NF68) neurofilament protein subunits. Increased immunoreactivity to NF P on NF200 and NF150 was detected in experimental DRC at 10 d, peaking by 20 d, and declining to near control levels by 28 d. Conversely, immunoreactivity to NF dP declined in experimental DRG beginning at 6 d, reaching a maximum decline at 10-16 d, and returning to near control levels by 28 d. Immunocytochemical changes were confirmed with biochemical studies on tissue homogenates that demonstrated an increase of immunoreactivity to NF-P and a decrease of reactivity to NF-dP in the experimental DRG. Changes in immunoreactivities to NF-P and NF-dP were observed only in the perikarya of large neurons and were closely associated with chromatolytic changes in these neurons. Marked enhancement of chromatolysis, as well as the immunoreactivities to NF-P and NF-dP, occurred following a proximal (left side) versus distal (right side) transection in the same animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106592 TI - Correlation of tumor plasminogen activator with peritumoral cerebral edema. A CT and biochemical study. AB - Extracts from 15 human cerebral tumors were tested by a fibrin-plate plasminogen dependent assay for levels of tumor plasminogen activator (TPA) activity. The TPA activity was correlated with the amount of perineoplastic edema as quantified on computerized tomography (CT) brain scanning. Analysis of the results showed a correlation coefficient of 0.72 when all tumors were included. Analysis of the nine tumors with the highest TPA levels showed a correlation coefficient of 0.96. One metastatic tumor had the highest level of TPA activity, equivalent to a pure 100-micrograms/ml solution of urokinase, and the greatest amount of cerebral edema on CT. Meningiomas generally had the next highest levels of TPA activity and edema, followed by astrocytomas of varying grades, which generally had the lowest level of TPA activity. However, three astrocytomas that had low TPA activity also had significant edema surrounding the tumor, indicating that more than one mechanism may be producing peritumoral edema. There was no correlation between tumor size and the amount of perineoplastic edema. These preliminary results suggest that TPA's may be involved in the production of perineoplastic cerebral edema and that treatment of patients with currently available plasminogen activator inhibitors may be successful in reducing peritumoral edema. PMID- 3106593 TI - Comparison of leukocytes labeled with indium-111-2-mercaptopyridine-N-oxide and indium-111 oxine for abscess detection. AB - Indium-111 leukocyte scanning has evolved into a practical and highly accurate method for the identification of infectious and inflammatory processes. The most commonly used agent for labeling leukocytes has been [111In]oxine. We have investigated a newer agent, 2-mercaptopyridine-N-oxide (Merc) at our institution which unlike oxine, allows us to label leukocytes in plasma, using a simple kit procedure. Of the 92 consecutive patients referred for detection or localization of an infectious process, autologous leukocytes of 55 patients were labeled with [111In]Merc, while those of the remaining 37 patients were labeled with [111In]oxine. The sensitivities for Merc and oxine procedures were 87% and 92%, respectively, while the respective specificities were 100% and 92%. We conclude that the [111In]Merc-labeled leukocytes are equally effective as [111In]oxine labeled leukocytes in detecting infectious processes. The use of [111In]Merc is advantageous over [111In]oxine for white blood cell labeling because of its easier preparation. PMID- 3106594 TI - Cause and significance of cold bone defects on indium-111-labeled leukocyte imaging. AB - Although photon deficient defects on bone scan have received a great deal of interest, such defects in bones on Indium-111 (111In) leukocyte imaging have not been as well recognized. We therefore undertook a retrospective review to determine the frequency and significance of such "cold" defects on 111In-labeled leukocyte imaging. Three hundred thirty-two scans on 290 patients were reviewed and 40 cases of decreased activity involving bone were found, for an incidence of 12%. The causes of the defects were: fracture (eight), nontraumatic avascular necrosis (eight), solid tumor (six), prostheses and other orthopedic hardware (four), advanced age (four), radiation (three), leukemia (two), osteomyelitis (two), myelofibrosis (one), postlaminectomy (one), and idiopathic (one). To determine the frequency of cold defects in osteomyelitis, all 15 cases of osteomyelitis in this series were reviewed and 12 showed increased activity, two were cold, and one was normoactive. Thus, 14% of cases of osteomyelitis presented as cold defects. We conclude that cold bone defects do occur on 111In-labeled leukocyte scans and that the causes of such defects are similar to those reported for bone and bone marrow scanning. PMID- 3106595 TI - New method for the chelation of indium-111 to monoclonal antibodies: biodistribution and imaging of athymic mice bearing human colon carcinoma xenografts. AB - B72.3, a murine monoclonal antibody (MAb) that reacts with 85% of human colon carcinomas as well as other epithelial neoplasias, was labeled with 111In using four chelating agents: 1-(p-isothiocyanatobenzyl)-DTPA (SCN-Bz-DTPA), isobutylcarboxycarbonic anhydride (MA-DTPA), cyclic anhydride (CA-DTPA), and 1-(p isothiocyanatobenzyl)-ethylenediaminetetraacetic acid (SCN-Bz-EDTA). Comparative biodistribution and imaging studies were performed in athymic mice bearing human colon carcinoma xenografts (LS-174T). Tumor uptake of radiolabel was very similar between the chelates (30% ID/g) and tumors were identified in scintigraphic images with all the chelate-antibody complexes. The uptake by normal organs, especially the liver, was greater for MA-DTPA, CA-DTPA, and SCN-Bz-EDTA chelate B72.3 IgG (1.3:1 to 2.5:1) in comparison to that found with the B72.3-SCN-Bz-DTPA (approximately 5:1) and abdominal organ, and uptake was very prominent on imaging with these chelate-MAb complexes but was virtually absent in the mice injected with B72.3-SCN-Bz-DTPA. Purification of the MAb-chelate complex by Sephadex G-50 chromatography followed by HPLC using a TSK-3000 column provided better subsequent biodistribution and also resulted in clearer images as compared to MAb chelate complexes purified by less rigorous purification protocols. We conclude that the 111In-SCN-Bz-DTPA complex is superior, at least when bound to MAb B72.3, to other chelate-complexes currently in use. PMID- 3106596 TI - Increasing the cost-effectiveness of research in clinical settings. PMID- 3106597 TI - The cost-quality balance: an analysis of quality, effectiveness, efficiency, and cost. AB - Present day fiscal pressures dictate the need for balancing nursing costs and quality concerns. This article presents logical and organized methodologies for interrelating quality compliance, patient volume, and nursing resource consumption and determining the costs associated with the delivery of quality nursing care. These methodologies provide the chief nursing officer a means for evaluating the impact of fiscal constraints on quality compliance and for judging any effectiveness/efficiency trade-offs. PMID- 3106598 TI - Bioavailability to rats of iron in six varieties of wheat grain intrinsically labeled with radioiron. AB - Bioavailability to anemic rats of iron in six varieties of wheat grain was assessed by a whole-body radioassay procedure. Intrinsically labeled kernels were harvested from plants grown in 59Fe-labeled nutrient solutions. The varieties used were selected from 18 varieties of field-grown wheat grain that were analyzed for iron, protein and phytate content. Concentrations of iron, phytate and protein in grain of field-grown varieties ranged from 34 to 55 ppm, 0.7 to 1.2% dry wt and 11.3 to 15.4% dry wt, respectively. In grain from varieties grown in nutrient solutions, iron, phytate and protein concentrations ranged from 35 to 50 ppm, 1 to 1.2% dry wt, and 13.8 to 16.8% dry wt, respectively. Depending on the variety of intrinsically labeled grain fed in test meals to anemic rats (hemoglobin averaged 5.8 g/dL), absorption of 59Fe ranged from about 62 to 74% of the dose; differences among varieties were not significant (P greater than 0.05). Rats fed 59Fe-labeled FeCl3 absorbed about 71% of the dose, which was similar to the average amount (69% of dose) absorbed by rats fed wheat. We concluded that selection of wheat varieties for increased yield or protein content has not adversely affected the bioavailability of iron in the grain. PMID- 3106600 TI - Influence of prior dietary protein intake on metabolism, DNA binding and adduct formation of 7,12-dimethylbenz[a]anthracene in isolated rat mammary epithelial cells. AB - These studies were designed to examine the influence of prior dietary protein intakes in rats on the ability of their isolated mammary cells to metabolize 7,12 dimethylbenz[a]anthracene (DMBA). Total metabolism of DMBA increased as dietary protein increased. After 6 h of incubation, water-soluble metabolites made only a minor (less than 12%) contribution to total DMBA metabolism. The binding of DMBA to isolated mammary cell DNA after 6 h of incubation from rats fed 15% dietary protein was 20% higher than binding from cells of rats fed 7.5% dietary protein. The increased binding in mammary epithelial cells from rats fed 15% protein was associated with an increase in the syn-dihydrodiol-epoxide adduct. The syn dihydrodiol-epoxide:deoxyadenosine adduct was the major contributor to binding. The present studies are consistent with a decrease in carcinogen activation in tissues obtained from animals fed diets limiting in protein. PMID- 3106599 TI - Metabolism of cysteine and cysteinesulfinate in rat and cat hepatocytes. AB - The metabolism of cysteine and cysteinesulfinate was studied in freshly isolated hepatocytes from fed rats and cats. In incubations of rat hepatocytes with cysteinesulfinate, the rate of hypotaurine plus taurine production was approximately the same as the rate of conversion of the 1-carbon of cysteinesulfinate to CO2. In contrast, no significant production of hypotaurine plus taurine occurred in incubations of cat hepatocytes with cysteinesulfinate. These data are consistent with the species difference in the activity of hepatic cysteinesulfinate decarboxylase, which converts cysteinesulfinate to hypotaurine. In incubations of either rat or cat hepatocytes with cysteine, no hypotaurine plus taurine production was detected. However, the 1-carbon of cysteine was converted to CO2 and the production of urea plus ammonia nitrogen was significantly increased over the rates observed in incubations of cells without substrate. Our results suggest that most cysteine oxidation by hepatocytes occurs by pathways that do not involve formation of cysteinesulfinate. PMID- 3106601 TI - Measurement of the quality of life in angina. PMID- 3106602 TI - Economics in hypertension management: cost and quality trade-offs. AB - Hypertension is a pervasive public health problem with enormous economic as well as medical consequences. Progress in developing more effective, safer and more convenient medications has been remarkable. Similarly, progress in focusing public and professional attention on hypertension has led to earlier treatment and undoubtedly contributed significantly to reduced stroke and cardiovascular mortality rates. Challenges in the next decade will be to resolve residual uncertainties about the balance of benefits and risk of treatment in mild diastolic hypertension and isolated systolic hypertension, and to develop incentives for maximizing the cost-effectiveness of treatment in those for whom treatment is, on balance, beneficial. Quality-of-life parameters will play prominent roles in clinical and policy decisions with respect to each of these challenges. PMID- 3106603 TI - Comparison of the antimicrobial susceptibility patterns of Pseudomonas aeruginosa isolates from two hospitals. PMID- 3106604 TI - Current concepts in nutrition: enteral tube feeding. PMID- 3106605 TI - Genotypic analysis of lymph node biopsies. PMID- 3106606 TI - Nutritional support for the infant with extrahepatic biliary atresia. AB - Some infants with biliary atresia obtain dramatic improvement for prolonged periods after the performance of hepatic portoenterostomy. Such infants may have life styles not substantially different from those of normal children. In others, the benefit from this operation, if any, is short lived. These infants are very vulnerable to the debilitating effects of severe, prolonged malabsorption and ultimately require orthotopic liver transplantation to sustain life. The physician caring for infants awaiting liver transplantation can do much, not only to prolong survival but to maintain satisfactory growth and development. The key consideration is to provide adequate nitrogen and nonnitrogen calories, liberally utilizing modern methods of enteral alimentation when necessary. In addition, attention must be directed toward several vitamin and mineral deficiencies, particularly those of the fat-soluble vitamins, that inevitably accompany severe malabsorption in children. Management of extrahepatic biliary atresia in infants is difficult and requires meticulous attention to details. Nevertheless, the long term cure of this disorder provided by liver transplantation makes their care a rewarding experience. PMID- 3106607 TI - Efficacy of beta-lactamase-resistant penicillin and influence of penicillin tolerance in eradicating streptococci from the pharynx after failure of penicillin therapy for group A streptococcal pharyngitis. AB - We studied the ability of dicloxacillin, a beta-lactamase-resistant penicillin, to eradicate persistent group A streptococci from the upper respiratory tract of children previously given penicillin V, and concomitantly assessed the role of antibiotic (penicillin and dicloxacillin) tolerance as a contributing factor. During a group A streptococcal pharyngitis outbreak, 66% of 324 children were found to be culture positive for group A streptococci. Ninety percent of these isolates were serotype M-1, T-agglutination pattern T-1. The treatment failure rate after initial orally administered penicillin treatment was 21% (42 of 204). These 42 children then received either a second course of penicillin V orally or a course of dicloxacillin. The resulting rates of failure to eradicate the homologous streptococcal serotype were 83% (20 of 24) and 50% (9 of 18), respectively (P less than 0.02). Of 189 streptococcal isolates tested by the gradient replicate plate method for penicillin tolerance, 18 (10%) were tolerant. In this study, penicillin-tolerant strains of group A streptococci were no more frequently isolated from children in whom initial penicillin treatment failed than from those who were successfully treated. Dicloxacillin tolerance was not a factor in failure of dicloxacillin therapy. These data, when evaluated with data from previous studies, suggest that reasons for failure to eradicate group A streptococci from the upper respiratory tract are complex, but dicloxacillin may be beneficial in some patients who fail to respond to orally administered penicillin therapy. PMID- 3106608 TI - Therapy for intractable diarrhea. PMID- 3106609 TI - Requirement of low oxygen tension for adaptation of a new isolate of Plasmodium falciparum to continuous in vitro culture. PMID- 3106610 TI - Cardiac histology of mice with experimental Chagas' disease. PMID- 3106611 TI - Autoimmunity in Chagas' disease. PMID- 3106612 TI - Growth of pathogenic Candida isolates anaerobically and under elevated concentrations of CO2 in air. AB - Individual isolates of seven potentially pathogenic yeast species in the genus Candida all grew to some extent in Eagle's minimal essential medium including serum under elevated concentrations of CO2 and in anaerobic gas jars. The C. glabrata and C. tropicalis isolates had the highest anaerobic growth rates and yields, the C. guilliermondii and C. parapsilosis isolates had the lowest, and the C. albicans, C. krusei and C. pseudotropicalis isolates gave intermediate growth rates and yields. The same relative abilities to grow anaerobically were seen when the seven isolates were cultured in liquid and on agar formulations of a peptone-glucose broth and two media containing Yeast Nitrogen Base. PMID- 3106613 TI - Candida lusitaniae septicemia in a patient on extended home intravenous hyperalimentation. AB - This is a report of the successful therapy of a case of Candida lusitaniae septicemia in a patient with short bowel syndrome who had been on home intravenous hyperalimentation for approximately 3 months when the infection developed. C. lusitaniae was isolated from multiple blood cultures taken over the course of 2 days. PMID- 3106614 TI - Pharmaceutical evaluation of hollow type suppositories. V. Preparation of valproic acid suppository and rectal absorption of valproic acid in rabbits. AB - Seven kinds of suppositories were constructed with oleaginous base materials (Witepsol H-15 (H-15) and E-85 (E-85]: a conventional type suppository containing valproic acid (VPA) mixed with E-85 (I), a conventional type suppository containing sodium salt of VPA (sodium valproate) (S-VPA) mixed with H-15 (II), hollow type suppositories containing VPA in the forms of oily liquid (free acid) (III), macrogol 1000 or 6000 mixture (IV or V), powder (S-VPA) (VI) and aqueous solution (S-VPA was dissolved in 0.9% NaCl solution) (VII) in each cavity. The content of VPA in type I was decreased considerably by volatility and type II was found to be hygroscopic. Therefore conventional type suppositories containing VPA or S-VPA were not of practical use, whereas III and VI prevented volatility of VPA and minimized the hygroscopic property of S-VPA. Plasma concentration of VPA was measured in rabbits after rectal administrations of III, IV, VI and VII. By using VI, the highest values of the mean of the peak plasma VPA concentration (Cmax) (49.8 +/- 2.6 micrograms/ml) and the mean of the area under the plasma concentration-time curve (AUC) (90.0 +/- 3.7 h X micrograms/ml) were obtained. The Cmax and the AUC estimated after administration of VII were not significantly different from those of VI. The Cmax and the AUC were lower with III than with IV, VI or VII but the extent of bioavailability (EBA) of III was about 80%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106615 TI - In vitro aldose reductase inhibitory activity of substituted N benzenesulfonylglycine derivatives. AB - A number of N-benzenesulfonylglycines, alanines, sarcosine, and prolines, which contain the minimum pharmacophore moieties necessary for aldose reductase inhibitory activity, were prepared and tested in the rat lens assay. In this assay, the benzenesulfonylglycines are considerably more potent than the corresponding alanine and sarcosine derivatives which, in turn, are more active than the proline analogues. Of the monosubstituted benzenesulfonylglycines, the 2 nitro and 4-amino derivatives were most active with 50% inhibitory concentration (IC50) values of 13 and 16 microM, respectively. The most potent derivatives evaluated were the beta- and alpha-naphthylenesulfonylglycines with IC50 values of 0.4 and 1.3 microM, respectively. The structure-activity data obtained from evaluation of the benzenesulfonylamino acids suggests that the aromatic ring and ring substituents, as well as the sulfonamide group and carboxylate moiety, all contribute to the inhibitory potency through direct interaction with complimentary binding sites present on aldose reductase. PMID- 3106616 TI - Ocular pharmacology of methazolamide analogs: distribution in the eye and effects on pressure after topical application. AB - The authors studied the relation between physicochemical properties and lowering of intraocular pressure (IOP) after topical application to rabbit in a series of 5-acylimino- and related imino-substituted analogs of methazolamide (Compound 4). All had Ki vs. carbonic anhydrase C of about 10(-8) M. The parent, methazolamide (5-acetyl) does not lower IOP, in contrast to the 5-CF3 acetyl compound (Compound 28). The 5-propionyl compound (6) unexpectedly was 3 times more water soluble than methazolamide and had 10 times greater CHCl3-buffer partition. The in vivo transcorneal permeability constant was 6 times greater than methazolamide. One hour after 1 drop of a 2% suspension of Compound 6, anterior aqueous concentration (in micromolar) was 69 (for methazolamide, 8), posterior aqueous was 19 and ciliary process was 17. IOP dropped 2.2 mm Hg and returned to normal in 4 hr. Other compounds in the series showed varying degrees of activity, ranging from Compound 28, which elicited an IOP fall of 3.5 mm Hg, to Compound 7, (n-pentyryl), for which the fall was 1.3 mm Hg. Also studied are substitutions for CH3 on the ring N at position 4. There are multiple criteria for in vivo activity; a major factor is the balance between water and lipid solubility. The methazolamide analogs are compared with benzothiazole-2-sulfonamides, another class under investigation as topical carbonic anhydrase inhibitors designed to treat glaucoma. PMID- 3106617 TI - Effect of increasing age on the endothelium-mediated relaxation of rat blood vessels in vitro. AB - The effect of age on cholinergic endothelium-mediated relaxation was examined in vitro using blood vessels from Fischer 344 rats ranging in age from 1 to 27 months. Although no differences were seen in contractile response to alpha adrenergic agonists, both aortic ring segments and perfused caudal arteries showed an increase in sensitivity of endothelium-mediated relaxation to the cholinergic agonist methacholine. This increase in sensitivity occurs between the ages of 6 and 12 months, with no further significant increase in sensitivity up to 27 months of age, suggesting it is a consequence of growth and development rather than old age. No difference with age in cholinergic relaxation was observed in the perfused mesenteric bed, indicating either no change of sensitivity in smaller resistance vessels or an effect that is hidden in this more complex perfused system. In contrast to findings with cholinergic stimulation, responses of the perfused caudal artery to the calcium ionophore A23187 were not altered with age. This suggests that the alteration with age in response to methacholine involves the muscarinic receptor or receptor-coupling mechanism rather than the generation of, or response to, endothelium-derived relaxing factor. PMID- 3106618 TI - Antagonism of calmodulin-stimulated adenylate cyclase by trifluoperazine, calmidazolium and W-7 in rat cerebellar membranes. AB - Ca++-calmodulin (CaM)-dependent stimulation of adenylate cyclase in rat cerebellar plasma membranes was demonstrated by removal of endogenous Ca++ and CaM and addition of exogenous Ca++ and CaM to the membranes. This CaM-dependent adenylate cyclase activity could be inhibited by calmidazolium and trifluoperazine in an apparently competitive manner, whereas the inhibition produced by W-7 was not competitive. The potency of the antagonists was strictly dependent upon the concentration of exogenous CaM present in the assay. Preincubation of membranes with exogenous CaM, followed by addition of anti-CaM agents, greatly reduced the inhibition of CaM-dependent adenylate cyclase activity. The potency of the anti-CaM agents was further decreased in membranes that had not been depleted of endogenous Ca++ and CaM (native membranes). The results suggest that optimal inhibition of CaM-dependent adenylate cyclase activity occurs upon simultaneous addition of exogenous CaM and anti-CaM agents to membranes depleted of endogenous Ca++ and CaM. Association of CaM with the catalytic unit of adenylate cyclase before introduction of CaM antagonists results in a CaM-C complex that is relatively refractory to inhibition by these anti-CaM agents. This CaM-catalytic unit complex probably exists in native membranes, rendering the antagonism of adenylate cyclase activity supported by endogenous Ca++-CaM essentially insensitive to low concentrations of CaM antagonists. PMID- 3106619 TI - Regulation of heme metabolism and monooxygeneses in liver and kidney: influence of therapeutically used gold compounds. AB - Two gold compounds, gold sodium thiomalate (AuTM) and auranofin (AF) are presently in clinical use in therapy of rheumatoid arthritis. The effects of varying doses of AF administered to rats by either the p.o. or the i.p. route on heme metabolism were determined. Twenty four hours after a single dose of AF, decreases in the sulfhydryl-containing enzymes, delta-aminolevulinic acid dehydratase and ferrochelatase activities were observed in the liver and kidneys. These decreases in heme biosynthetic enzymes were accompanied by decreases in cytochrome P-450-dependent enzymic activities and increases in microsomal heme oxygenase activity. These changes were observed with AF dosages as low as 5 mg/kg, with maximal changes occurring at a p.o. dose of about 15 mg of AF per kg and an i.p. dose of 5 to 10 mg of AF per kg. Dose-response studies with AuTM showed that maximal changes in heme metabolism occur at a lower dose of AF than of AuTM, even though AF was administered p.o. and AuTM was administered parenterally. In addition, the kidneys appeared to be more susceptible to the inhibitory effects of the two chrysotherapeutic agents than did the liver. The present studies demonstrate the p.o. drug AF affects heme metabolism in a manner similar to that reported previously with the parenterally administered AuTM. PMID- 3106620 TI - Effects of sulfinpyrazone and its metabolite G25671 on platelet activation and desensitization and on bronchoconstriction induced by the prostaglandin endoperoxide analog U46619. AB - Sulfinpyrazone (100 microM) and its thioether metabolite G25671 (50 microM) suppressed arachidonic acid-induced platelet aggregation, thromboxane (Tx) B2 formation and ATP release. Platelet activation by the endoperoxide analog U46619 also was prevented by sulfinpyrazone or G25671 (0.3-1 mM). Previous studies have shown that human platelets pre-exposed to arachidonic acid or to U46619 and then washed and resuspended failed to respond to a second challenge by both arachidonic acid and U46619; desensitization by arachidonic acid and U46619 occurred at a site sensitive to endoperoxides/Tx receptor antagonists; and the desensitizing effects of U46619 were direct, whereas those of arachidonic acid were mediated by a cyclooxygenase-dependent metabolite. We now demonstrate that the presence of sulfinpyrazone or G25671 during platelet exposure to arachidonic acid or U46619 prevented desensitization. We also studied the threshold aggregating concentration of arachidonic acid and U46619 in healthy subjects before and after treatment with sulfinpyrazone and we found a good correlation between ex vivo and in vitro findings. We finally examined the actions of sulfinpyrazone and G25671 on the bronchoconstriction in vivo and parenchymal lung strip contraction in vitro induced by U46619. Neither drug had any preventive effect. Our results demonstrate that sulfinpyrazone and its metabolite G25671 are not only cyclooxygenase inhibitors but can also act as endoperoxide/Tx antagonists and indicate clearly that antagonism of U46619 by both drugs is selective for platelets. PMID- 3106621 TI - Partial purification and characterization of Naegleria fowleri beta-glucosidase. AB - Naegleria fowleri cells, grown axenically, contain high levels of beta-D glucosidase which catalyzes the hydrolysis of 4-methylumbelliferyl-beta-D glucopyranoside (4MUGlc) (Km, 0.9 mM), octyl-beta-D-glucoside (Km, 0.17 mM), and p-nitrophenyl-beta-D-glucopyranoside at relative rates of 1.00, 2.88, and 1.16, respectively (substrate concentration, 3.0 mM). When the amebae are subjected to freeze-thawing, sonication, and centrifugation (100,000 g, 1 h), 85% of the beta glucosidase activity appears in the supernatant fraction. The beta-glucosidase was purified 40-fold (34% yield) using a combination of chromatographic steps involving DE-52 cellulose, concanavalin A-Sepharose, and hydroxylapatite followed by isoelectric focusing. The predominant soluble beta-D-galactosidase activity in the Naegleria extract copurifies with the beta-D-glucosidase; the two activities have the same isoelectric point (pI, 6.9), similar heat stabilities, are both inhibited by lactobionic acid (Ki, 0.40 mM), and exhibit optima at pH 4.5, indicating that they are probably the same enzyme. The Naegleria beta-D glucosidase has an apparent molecular weight of 66,000, a Stokes radius of 25 A, and a sedimentation coefficient of 4.2S. The beta-glucosidase is not inhibited by conduritol beta-epoxide or galactosylsphingosine but is completely inhibited by 1.25 mM bromo conduritol beta-epoxide. The latter compound, when present in the growth medium, inhibits the growth of the organism and profoundly alters its ultrastructure, the main effect being the apparent inhibition of cytokinesis and the generation of multinucleate cells. The issue of the role of the beta glucosidase in the metabolism of the ameba and its possible role in pathogenic mechanisms are discussed. PMID- 3106622 TI - The fine structure of the paralabial organelle in the rumen ciliate Ophryoscolex purkinjei Stein, 1858. AB - The paralabial organelle of the rumen ciliate Ophryoscolex purkinjei, located on the ventral side of the ciliophor, is a highly specialized part of the somatic cortex. It consists of alternating rows of short modified cilia and thin pellicular folds which form a ridge-like structure. The central "top kinety" is composed of monokinetids which bear cilia with 9 + 2 axonemes and 2 microns in length. The top kinety is accompanied by a comb-shaped fold on its distal side and by a broad wedge-shaped fold on its proximal side. To both sides there follow two or three lateral kineties made of dikinetids. The anterior kinetosome of each pair bears a clavate cilium, only 0.5-0.7 micron in length and with a 9 + 0 axoneme while the cilium of the posterior kinetosome is even shorter. Lateral folds with numerous microtubules cover these lateral kineties and rows of barren basal bodies. The fine structure of this supposed sensory organelle show a basic pattern in four other ophryoscolecids, and its increasing complexity parallels the suggested phylogenetic line of evolution of these ciliates. PMID- 3106623 TI - Chromosomal aberrations in an ionizing radiation-sensitive mouse lymphoma mutant cells exposed to gamma-rays and 4-nitroquinoline-1-oxide. PMID- 3106624 TI - [A misleading manifestation of urogenital schistosomiasis in man]. AB - Lesions of seminal vesicles during urogenital schistosomiasis are a frequent finding but their manifestation as a palpable mass is a rare feature. An exceptional case of a large schistosomial spermatocyst is reported in which diagnosis was by histopathology. PMID- 3106626 TI - Short-term effects of FSH in vitro on granulosa cells of individual sheep follicles. AB - In Romanov ewes at Day 13 or 14 of the cycle, granulosa cells originating from individual follicles were studied in short-term incubations for aromatase activity and thymidine incorporation. The study was performed on 76 follicles of different sizes (2-7 mm diameter) and degree of atresia, as assessed by histological examination of smears of granulosa cells. As atresia progressed, the labelling index and aromatase activity of granulosa cells decreased. In normal follicles, when follicular diameter increased, the labelling index decreased, while aromatase activity of granulosa cells and oestradiol-17 beta concentration in follicular fluid increased. There was a negative relationship between oestradiol concentration in follicular fluid and the labelling index of granulosa cells in vitro (rs = -0.75; P less than 0.01), suggesting an inverse relationship between growth and differentiation of granulosa cells in normal sheep follicles. In normal small and medium-sized follicles (2-6 mm), incubation with FSH (100 ng/ml) for 2 h increased significantly the labelling index of granulosa cells. In normal medium-sized follicles (4-6 mm), incubation with FSH (50 ng/ml) for 1 h decreased the aromatase activity of granulosa cells. From these results, it is suggested that FSH acts mainly on cells in the G1 phase of the cell cycle, which are steroidogenically active, and makes them move into the S phase where their steroidogenic activity is temporarily inhibited. PMID- 3106625 TI - Reproductive hormone secretion and testicular growth in bull calves actively immunized against testosterone and oestradiol-17 beta. AB - Groups of bull calves received a primary immunization against testosterone (Group T; N = 7) or oestradiol-17 beta (Group E; N = 9) at 3 months of age and booster injections on four occasions at approximately 2 month intervals. Controls (Group C, N = 7) were immunized against human serum albumin alone using the same protocol. Immunity was achieved against both steroids as judged by the secondary antisteroid antibody titres in Group T (730 +/- 231; reciprocal of titre) and Group E (12,205 +/- 4366) bulls; however, peak antibody titres generally declined with successive booster injections. Mean plasma concentrations of LH, FSH and testosterone during the period from 3 to 10 months of age were higher (P less than 0.05) in Group T bulls than in Groups C and E. Group T bulls had larger testes compared with controls from 6 months of age onwards. At castration at 14 months of age, testes of Group T bulls were heavier (P less than 0.05) than those of Groups C and E (179 +/- 13, 145 +/- 8 and 147 +/- 6 g, respectively). At 10 months of age, there were no differences among treatment groups in LH responses to LHRH, but the testosterone responses were greater (P less than 0.05) in bulls in Group T (26.2 +/- 4.9 ng/ml) and Group E (16.6 +/- 1.8 ng/ml) compared with those in Group C (6.9 +/- 0.6 ng/ml). Testosterone responses to hCG determined at 13 months of age were also greater (P less than 0.05) in Groups T and E relative to controls. At 14 months of age daily sperm production rates per bull (X 10(-9)) were higher (P less than 0.10) in Group T bulls (2.2 +/- 0.1) than those in Groups C (1.6 +/- 0.2) and E (1.6 +/- 0.1). These results indicate that early immunity against testosterone is associated with increased gonadotrophin secretion and accelerated growth of the testes in prepubertal bulls. Also, chronic immunity against testosterone or oestradiol-17 beta enhances the steroidogenic response of bull testes to gonadotrophic stimulation. If the above responses observed in young bulls are shown to be sustained, then immunity against gonadal steroids early in life may confer some reproductive advantage in mature animals. PMID- 3106627 TI - Disparate effects of endogenous and exogenous oestradiol on luteal phase function in women. AB - Five normally ovulating women were induced to superovulate with pulsatile 'pure' FSH (28 i.u. every 3 h by a s.c. pump), and another 5 women were given an i.m. injection of 10 mg oestradiol benzoate in the late follicular phase. Serum oestradiol concentrations in the luteal phase were similar in both groups and significantly higher than in corresponding control cycles. The luteal phase was of shorter duration in the FSH (11.2 +/- 0.7 days) than in the control (13.4 +/- 0.2 days) and the oestrogen-treatment cycles (13.4 +/- 0.7 days) (P less than 0.05, mean +/- s.e.m.). FSH cycles had significantly lower early luteal serum LH (Day 1: 5.3 +/- 1.5 mi.u./ml) and mid-luteal serum progesterone values (35.4 +/- 3.5 nmol/l) compared with the control (27.8 +/- 5.8 mi.u./ml and 65.4 +/- 5.7 nmol/l, respectively) and oestrogen treatment cycles (25.3 +/- 8.3 mi.u./ml and 59.1 +/- 8.4 nmol/l, respectively) (P less than 0.05, mean +/- s.e.m.). These results suggest that, in hyperstimulated cycles, the luteal phase can be disrupted even without follicle aspiration, and that suppression of endogenous LH secretion may be responsible. PMID- 3106628 TI - Effect of photoperiod on LH, FSH and prolactin patterns in ovariectomized oestradiol-treated heifers. AB - Angus and Angus crossbred heifers were ovariectomized, treated with oestradiol implants and randomly assigned to the natural photoperiod of fall to spring for 43 degrees N latitude or extra light simulating the photoperiod of spring to fall. Weekly blood samples were taken for 6 months (fall to spring equinox). All heifers were cannulated every 4 weeks and blood samples were taken for 4 h at 15 min intervals. Sera were assayed for LH, FSH, prolactin and oestradiol. In samples taken weekly, serum LH and FSH concentrations were higher while serum prolactin was lower in heifers exposed to natural photoperiod. There was a photoperiod X time interaction for both FSH and prolactin with concentrations diverging as photoperiod diverged. Circulating concentrations of oestradiol were not different between groups. In samples taken every 4 weeks at 15-min intervals, baseline concentrations of LH and FSH and LH pulse amplitude were higher while prolactin pulse frequency was lower in heifers exposed to natural photoperiod. There was a photoperiod X time interaction for each of these pulsatile characteristics. The correlation between LH and prolactin concentrations estimated from the 15-min samples differed between the two photoperiod treatment groups. The pooled correlation coefficient (r) was -0.12 under natural photoperiod and +0.50 under extra light. There was also a photoperiod X time interaction with negative correlations occurring when photoperiod was decreasing and positive correlations occurring when photoperiod was increasing. These results support the hypothesis that photoperiod alters serum concentrations of LH, FSH and prolactin in cattle. PMID- 3106629 TI - Gonadotrophin secretion and pituitary responsiveness to LHRH in castrated and intact male rabbits exposed to different photoperiods. AB - Adult male wild rabbits were exposed to at least 16 weeks of 16L:8 D before experiments began. Plasma LH and FSH concentrations increased significantly (P less than 0.001) when rabbits were castrated in 16L:8D but declined when rabbits were transferred to 8L:16D. Concentrations had returned to normal for castrated rabbits in 16L:8D by 74 days after the start of the 8L:16D treatment. Treatment of intact male rabbits with an injection of LHRH before and after transfer to short daylengths caused a transient increase in plasma LH which lasted 50-80 min and this produced a concomitant rise in plasma testosterone. The daylength change had no effect on this response even though testicular size declined after the transfer to short daylengths. Rabbits moulted in response to exposure to 8L:16D. This suggests that hypothalamic activity responds to photoperiod and that changes in pituitary responsiveness to LHRH and steroid negative feedback are unimportant. PMID- 3106630 TI - Gold induced ulcerative proctitis: report and review of the literature. AB - A case of ulcerative proctitis complicating chrysotherapy for rheumatoid arthritis and a literature review of gold induced enterocolitis is presented. Only 26 patients have been reported with this complication. No specific therapy is available, except supportive measures and cessation of gold therapy. PMID- 3106631 TI - Osteonecrosis, fractures, and protrusio acetabuli secondary to x-irradiation therapy for prostatic carcinoma. AB - Two years after pelvic irradiation for prostatic cancer, bilateral protrusio acetabuli and collapse of the right femoral head requiring prosthetic arthroplasty developed in a 73-year-old man with chronic rheumatoid arthritis. There was no evidence of metastases. Histologic evaluation showed empty lacunae in the bone but no evidence of obliterative endarteritis. Osteonecrosis and pathologic fractures constitute a rare complication of high voltage irradiation. PMID- 3106632 TI - Hematuria in patients with rheumatoid arthritis receiving gold and D penicillamine. AB - We reviewed the urinalyses from 2 multicenter controlled randomized trials, one comparing moderate and low dose D-penicillamine to placebo and another comparing gold sodium thiomalate (GSTM), auranofin (AF) and placebo. In the D-penicillamine trial 30% of the 40 patients taking placebo, 34% of the 70 patients receiving 125 mg/day of D-penicillamine and 31% of the 61 patients receiving 500 mg of D penicillamine had recurrent hematuria. In the GSTM/AF trial, 35% of the 43 placebo treated patients, 35% of the 54 GSTM treated patients and 30% of the 64 AF treated patients had hematuria. No significant difference in the frequency of hematuria between the groups in either trial was apparent. These findings suggest that the traditionally held belief that gold and D-penicillamine cause hematuria should be reconsidered. PMID- 3106633 TI - Cost-effectiveness of investigations for invasive bladder cancer. AB - The results of diagnostic and staging investigations in consecutive cases of invasive transitional cell carcinoma of the bladder are reviewed. Urine culture, urine cytology and intravenous urography had positive results in a high percentage of cases. As diagnostic investigations they are cost-effective but certainly do not remove the obligation to perform cystoscopy and examination under anaesthetic. Isotopic bone scan and liver scan showed metastases in 4 and one cases respectively and only when there were clinical signs of disseminated disease. Chest X-ray showed metastases in one case. These investigations are not cost-effective. Lymphangiography was positive in 12 of the 94 cases and, although expensive (pounds 70), is still a staging investigation of value in planning treatment. PMID- 3106634 TI - Systemic lupus erythematosus in child with autoimmune thrombocytopenic purpura and circulating lupus anticoagulant. PMID- 3106635 TI - Examination of lochia as an aid to the early diagnosis of bovine brucellosis. AB - The standard technique for diagnosing bovine brucellosis is the serological examination of blood samples. As affected females may excrete large numbers of the Brucella organism in the lochia, the bacteriological and smear examination of such material appeared to be a suitable alternative for early diagnosis. Of the lochia samples collected from 210 cows and heifers within 12-24 h after parturition or abortion, 10.9% were bacteriologically positive. Only 70% of these could be diagnosed correctly as positive by microscopic examination. This technique also resulted in 3.3% false negative and 1.4% false positive diagnoses. Results of the serological examinations of blood, collected simultaneously with the lochia samples, correlated fairly well with those obtained microscopically. Culture of lochia samples on a suitable medium appears to be the method of choice, when dealing with the early diagnosis of bovine brucellosis. PMID- 3106637 TI - Transfer of mitochondrial DNA from the northern red-backed vole (Clethrionomys rutilus) to the bank vole (C. glareolus). AB - Using a silver staining method to detect DNA fragments produced by restriction enzymes, it was possible to compare mitochondrial DNAs (mtDNAs) from 85 individuals of the bank vole (Clethrionomys glareolus) trapped at 25 localities in Fennoscandia. There are two distinctly different mtDNA lineages, one occurring in southern and central Fennoscandia and the other in the northern parts. A fragment comparison method shows about 12.7% nucleotide sequence divergence between these two lineages. This major difference between animals of the same species could theoretically be explained by intraspecific lineage survivorship independent of species hybridization, or by introduction of an atypical mtDNA via hybridization with a closely related species. Analysis of mtDNAs from the two other Clethrionomys species present in Fennoscandia (C. rutilus and C. rufocanus) shows that the mtDNA of northern C. glareolus is very similar to that of C. rutilus and that the mtDNA lineages of these two species cluster together in a phenogram, with small genetic distances among them. By contrast, electrophoresis of proteins encoded by 17 nuclear loci reveals fixed allelic differences between these two species at 8 loci. Hence the presence of two distinctly different mtDNA lineages within C. glareolus may be a consequence of a limited episode of hybridization between C. glareolus and C. rutilus, probably during the postglacial recolonization of Fennoscandia 8000-13,000 years ago. PMID- 3106636 TI - An amiloride-sensitive Na+ conductance in the basolateral membrane of toad urinary bladder. AB - Exposing the apical membrane of toad urinary bladder to the ionophore nystatin lowers its resistance to less than 100 omega cm2. The basolateral membrane can then be studied by means of transepithelial measurements. If the mucosal solution contains more than 5 mM Na+, and serosal Na+ is substituted by K+, Cs+, or N methyl-D-glucamine, the basolateral membrane expresses what appears to be a large Na+ conductance, passing strong currents out of the cell. This pathway is insensitive to ouabain or vanadate and does not require serosal or mucosal Ca2+. In Cl-free SO2-(4) Ringer's solution it is the major conductive pathway in the basolateral membrane even though the serosal side has 60 mM K+. This pathway can be blocked by serosal amiloride (Ki = 13.1 microM) or serosal Na+ ions (Ki approximately 10 to 20 mM). It also conducts Li+ and shows a voltage-dependent relaxation with characteristic rates of 10 to 20 rad sec-1 at 0 mV. PMID- 3106638 TI - Interrelatedness of 5S RNA sequences investigated by correspondence analysis. AB - Correspondence analysis (a form of multivariate statistics) applied to 74 5S ribosomal RNA sequences indicates that the sequences are interrelated in a systematic, nonrandom fashion. Aligned sequences are represented as vectors in a 5N-dimensional space, where N is the number of base positions in the 5S RNA molecule. Mutually orthogonal directions (called factor axes) along which intersequence variance is greatest are defined in this hyperspace. Projection of the sequences onto planes defined by these factorial directions reveals clustering of species that is suggestive of phylogenetic relationships. For each factorial direction, correspondence analysis points to regions of "importance," i.e., those base positions at which the systematic changes occur that define that particular direction. In effect, the technique provides a rapid determination of group-specific signatures. In several instances, similarities between sequences are indicated that have only recently been inferred from visual base-to-base comparisons. These results suggest that correspondence analysis may provide a valuable starting point from which to uncover the patterns of change underlying the evolution of a macromolecule, such as 5S RNA. PMID- 3106640 TI - Molecular evolution of the Saccharomyces cerevisiae histone gene loci. AB - The core histone genes of Saccharomyces cerevisiae are arranged as duplicate nonallelic sets of specifically paired genes. The identity of structural organization between the duplicated gene pairs would have its simplest evolutionary origin in the duplication of a complete locus in a single event. In such a case, the time since the duplication of one of the genes should be identical to that since duplication of the gene adjacent to it on the chromosome. A calculation of the evolutionary distances between the coding DNA sequences of the histone genes leads to a duplication paradox: The extents of sequence divergence in the silent component of third-base positions for adjacent pairs of genes are not identical. Estimates of the evolutionary distance between the two H3-H4 noncoding intergene DNA sequences are large; the divergence between the two separate sequences is indistinguishable from the divergence between either of the regions and a randomly generated permutation of itself. These results suggest that the duplication event may have occurred much earlier than previously estimated. The potential age of the duplication, and the attractive simplicity of the duplication of both the H3-H4 and the H2A-H2B gene pairs having taken place in a single event, leads to the hypothesis that modern haploid S. cerevisiae may have evolved by diploidization or fusion of two ancient fungi. PMID- 3106641 TI - Qualitative and quantitative variability in different classes of proteins: comparison of mouse and rat. AB - Proteins of membranes and cytosols were extracted from the livers and brains of mice (inbred strain DBA/6J) and rats (inbred strain DA/Han) and separated by two dimensional electrophoresis (2-DE). The 2-DE patterns were compared with regard to qualitative (spot position) and quantitative (spot intensity) characteristics of the proteins of these two species. The following results were obtained: Brain had more (higher percentage) conservative proteins (proteins found in both mice and rats) than liver; plasma membranes had more conservative proteins than the cytosols; organ-unspecific proteins contained more conservative proteins than relatively organ-specific proteins; the pattern of distribution of genetic variability among different classes of proteins represented by findings 1-3 was the same for the qualitative and quantitative characteristics of the proteins; and some observations indicated that quantitative variability occurred more frequently among proteins than did qualitative variability. Our conclusion is that regulatory sequences in the DNA (regulatory genes) are subjected to functional constraints that differ in strength among different classes of proteins by the same ratios as the constraints acting on the structural genes. The overall effect of the selective pressure is, however, less stringent for regulatory genes than for structural genes. The results obtained here by comparing two different species are very similar to previous results we obtained by studying different subspecies (inbred strains of the mouse). From this finding arises a new concept: the study of molecular evolution on the basis of different classes of proteins. Our results were compared with data from the literature that were obtained in part from studies on cultured cells. The comparison suggested that cultured cells have lost their tissue-specific proteins, and so generate predominantly extremely conservative proteins. PMID- 3106639 TI - The secondary structure of human 28S rRNA: the structure and evolution of a mosaic rRNA gene. AB - We have determined the secondary structure of the human 28S rRNA molecule based on comparative analysis of available eukaryotic cytoplasmic and prokaryotic large rRNA gene sequences. Examination of large-rRNA sequences of both distantly and closely related species has enabled us to derive a structure that accounts both for highly conserved sequence tracts and for previously unanalyzed variable sequence tracts that account for the evolutionary differences in size among the large rRNAs. Human 28S rRNA is composed of two different types of sequence tracts: conserved and variable. They differ in composition, degree of conservation, and evolution. The conserved regions demonstrate a striking constancy of size and sequence. We have confirmed that the conserved regions of large-rRNA molecules are capable of forming structures that are superimposable on one another. The variable regions contain the sequences responsible for the 83% increase in size of the human large-rRNA molecule over that of Escherichia coli. Their locations in the gene are maintained during evolution. They are G + C rich and largely nonhomologous, contain simple repetitive sequences, appear to evolve by frequent recombinational events, and are capable of forming large, stable hairpins. The secondary-structure model presented here is in close agreement with existing prokaryotic 23S rRNA secondary-structure models. The introduction of this model helps resolve differences between previously proposed prokaryotic and eukaryotic large-rRNA secondary-structure models. PMID- 3106642 TI - Recruitment of lysozyme as a major enzyme in the mouse gut: duplication, divergence, and regulatory evolution. AB - Two major types of lysozyme c (M and P) occur in the mouse genus, Mus, and have been purified from an inbred laboratory strain (C58/J) of M. domesticus. They differ in physical, catalytic, and antigenic properties as well as by amino acid replacements at 6 of 49 positions in the amino-terminal sequence. Comparisons with four other mammalian lysozymes c of known sequence suggest that M and P are related by a gene duplication that took place before the divergence of the rat and mouse lineages. M lysozyme is present in most tissues; achieves its highest concentration in the kidney, lung, and spleen; and corresponds to the lysozyme partially sequenced before from another strain of M. domesticus. In M. domesticus and several related species, P lysozyme was detected chiefly in the small intestine, where it is probably produced mainly by Paneth cells. A survey of M and P levels in 22 species of muroid rodents (from Mus and six other genera) of known phylogenetic relationships suggests that a mutation that derepressed the P enzyme arose about 4 million years ago in the ancestor of the housemouse group of species. Additional regulatory shifts affecting M and P levels have taken place along lineages leading to other muroid species. Our survey of 187 individuals of wild house mice and their closest allies reveals a correlation between latitude of origin and level of intestinal lysozyme. PMID- 3106643 TI - DNA synthesis in pulmonary alveolar macrophages and type II cells: effects of ozone exposure and treatment with alpha-difluoromethylornithine. AB - An increase in the number of pulmonary alveolar macrophages (AM) can be induced by a number of toxic insults to the lung, including ozone, an important photochemical oxidant air pollutant. This increase could arise from an influx of monocytes from the vascular or interstitial compartments, or from proliferation of AM in situ. While proliferation of alveolar type II cells after oxidant exposure has been well documented, it is not clear whether AM are also capable of this response. Rats were exposed to air or to 0.12, 0.25, or 0.50 ppm ozone for 1, 2, 3, 7, or 14 d, 20 h/d. The labeling index in both AM and type II cells increased about 10-fold after 2 d of exposure to 0.25 and 0.50 ppm of ozone, but returned to control levels by the end of 1 wk of exposure. These changes closely paralleled the temporal and dose-response characteristics of changes in total lung DNA synthesis. alpha-Difluoromethylornithine (DFMO) administered to rats during a 2-d exposure to 0.50 ppm ozone did not inhibit the ozone-induced increase in labeling index in AM or type II cells, although evidence of inhibition of lung ornithine decarboxylase activity was obtained, and the ozone induced increase in total lung DNA synthesis was inhibited by 23%. These results suggest that, like type II cells, AM are capable of entering the cell cycle and synthesizing new DNA in situ in response to short-term exposure to environmentally relevant doses of ozone, and that the ozone-induced stimulation of DNA synthesis in these cell types was refractory to inhibition by DFMO. PMID- 3106644 TI - Influence of polyunsaturated fatty acid supplementation and membrane fluidity on ozone and nitrogen dioxide sensitivity of rat alveolar macrophages. AB - The phospholipid polyunsaturated fatty acid (PUFA) content and the membrane fluidity of rat alveolar macrophages were modified dose-dependently and in different ways. This was done to study the importance of both membrane characteristics for the cellular sensitivity toward ozone and nitrogen dioxide. Cells preincubated with arachidonic acid (20:4) complexed to bovine serum albumin (BSA) demonstrated an increased in vitro sensitivity versus ozone and nitrogen dioxide. The phenomenon was only observed at the highest 20:4 concentrations tested, whereas the membrane fluidity of the 20:4-treated cells already showed a maximum increase at lower preincubation concentrations. Hence it could be concluded that the increased ozone and nitrogen dioxide sensitivity of PUFA enriched cells is not caused by their increased membrane fluidity, resulting in an increased accessibility of sensitive cellular fatty acid moieties or amino acid residues. This conclusion receives further support from other observations. These results strongly support the involvement of lipid oxidation in the mechanism(s) of toxic action of both ozone and nitrogen dioxide in an intact cell system. PMID- 3106645 TI - Long-chain acyl-coenzyme A synthetase in rat brain myelin. AB - Long-chain acyl-CoA synthetase (EC 6.2.1.3), an enzyme(s) that activates fatty acids prior to incorporation into phospholipids and other substances, has been detected in highly purified myelin from rat brain stem. The high levels relative to microsomes (11% and 15% for oleate and arachidonate, respectively) tended to preclude contamination by the latter membrane as the source of activity. Additional evidence came from sequential purification and mixing experiments. Km values were not appreciably different for the two substrates with the two membranes, but Vmax values were approximately 2-4-fold greater for arachidonate in both membranes. Triton X-100 increased activity somewhat in myelin but not in microsomes; with arachidonate as substrate it reduced activity in the latter. Heat inactivation studies and pH profiles suggested the presence of two different enzymes, as previously shown for other tissues. PMID- 3106646 TI - Evaluating trauma care: the TRISS method. Trauma Score and the Injury Severity Score. AB - Evaluation of trauma care must be an integral part of any system designed for care of seriously injured patients. However, outcome review should offer comparability to national standards or norms. The TRISS method offers a standard approach for evaluating outcome of trauma care. Anatomic, physiologic, and age characteristics are used to quantify probability of survival as related to severity of injury. TRISS offers a means of case identification for quality assurance review on a local basis, as well as a means of comparison of outcome for different populations of trauma patients. Methods for calculating statistics associated with TRISS are presented. The Z and M statistics are explained with the nonstatistician in mind. We feel this article is a source for those interested in developing or upgrading trauma care evaluation. PMID- 3106647 TI - Pilot survey of urinary porphyrins from persons transiently exposed to a PCB transformer fire. AB - In rats and humans chronically exposed to large amounts of PCB (polychlorinated biphenyls) and PCDF (polychlorinated dibenzofurans), the urinary excretion of uroporphyrin and coproporphyrin are altered. However, porphyrin excretion in humans after acute transient low level exposure has not been evaluated. Following such an exposure in which bystanders and firefighters were in contact with smoke from a PCB transformer fire, we surveyed 90 self-referred individuals by questionnaire and by determining single 24 hour urinary excretion of uroporphyrin and coproporphyrin 2-4 weeks after the fire. Questionnaire variables that assessed exposure were not associated with the magnitude of either uroporphyrin or coproporphyrin excretion. Uroporphyrin excretion was slightly elevated in nine subjects (range 66-106 micrograms/24 hours, normal less than 60), which is much less than in clinical cases of porphyria cutanea tarda. Uroporphyrin excretion was inversely correlated with coproporphyrin excretion (r = -0.3844, p = 0.0002). For 5 subjects (3 with elevated initial uroporphyrin excretion) retested at 3-4 weeks after the fire, all 5 showed increases in uroporphyrin and decreases in coproporphyrin excretion when compared to initial determinations. These two reciprocal relationships would be the expected result from inhibition of uroporphyrinogen decarboxylase, a known experimental effect of PCB and PCDF in mice. Overall, urinary porphyrin excretions were not altered or sensitive measures of exposure. PMID- 3106648 TI - Long-term follow-up of severe protein-energy malnutrition in Eastern Zaire. PMID- 3106649 TI - Expression of interferon-inducible genes in RD-114 cells. AB - RD-114 is a cell line which is partially responsive to interferon (IFN). Although both IFN-alpha and IFN gamma inhibit production of the resident retrovirus, they do not inhibit replication of other viruses, such as vesicular stomatitis virus and encephalomyocarditis virus, in these cells. In the studies reported here, we studied the characteristics of induction of seven IFN-inducible mRNAs in RD-114 cells. We observed that mRNAs 561, 6-16, 1-8, 2A, and 6-26 have similar induction characteristics in RD-114 cells and in HeLa cells, a fully responsive line. mRNA 2'-5'-oligo-adenylate synthetase (2-5(A) synthetase), however, was induced more efficiently by IFN-alpha in HeLa cells than in RD-114 cells. The same was true for the induction of metallothionein II mRNA by IFN-gamma. However, the latter mRNA was induced equally strongly in both lines when ZnCl2 was used as the inducer, suggesting that the gene is not defective in RD-114 cells. Although IFN alpha induced 2-5(A) synthetase mRNA poorly and IFN-gamma did not induce it at all in these cells, a mixture of IFN-alpha and IFN-gamma induced this mRNA quite effectively, to a level of induction comparable to that in HeLa cells. Only 1 U of IFN-gamma per ml was sufficient to elicit this synergism, and the data suggested that an IFN-gamma-inducible protein was needed for this process. Induction of mRNA 561 by IFN-alpha in RD-114 cells, unlike that in HeLa cells, did not need ongoing protein synthesis. Once induced, this mRNA turned over rapidly in both cell lines, and this turnover could be slowed down by inhibiting protein synthesis in either cell line. IFN-induced mRNAs, such as 561 and 1-8, were polysome associated in IFN-treated RD-114 cells, suggesting that they were actively translated. Therefore, it is unlikely that the products of these IFN inducible genes, by themselves, mediate the inhibition of replication of those viruses which are insensitive to IFN action in RD-114 cells. PMID- 3106651 TI - Re: Preliminary observations on the results of combined temporary 192iridium implantation and external beam irradiation for carcinoma of the prostate. PMID- 3106652 TI - Percutaneous management of renal pelvic tumors: a treatment option in selected cases. AB - Nine patients with renal pelvic transitional cell carcinomas were selected for treatment with percutaneous resection because of a solitary kidney (3), bilateral synchronous disease (1), renal insufficiency (1), poor surgical risk (2) or preoperative evidence of a single, low grade, superficial tumor (2). Eight patients underwent second-look procedures 2 to 28 days postoperatively, at which time 6 received neodymium: YAG laser irradiation. Supplemental intracavitary therapy through the nephrostomy tube was given in 6 patients (mitomycin C in 1 and bacillus Calmette-Guerin in 5). Of those patients 2 had third-look procedures. Five patients remain free of recurrence with a followup of 3 to 28 months (mean 9.5 months). In the other 4 patients there was recurrent disease in the renal pelvis (3) or reappearance of positive cytology studies (1) 4 to 5 months postoperatively. Extrarenal tumor recurrence was not observed. Percutaneous surgery provided adequate information to assess tumor architecture, grade, invasiveness and multifocality, and the presence of contiguous mucosal abnormalities, which, along with positive cytology and a history of or concurrent tumors in other segments of the urinary tract, increased the likelihood of tumor recurrence. Second-look procedures appeared to be useful to assess the effectiveness of the initial procedure and to remove any residual disease. Our results suggest that percutaneous surgery can provide results similar to those of an open conservative operation, although further investigation is needed to determine the ultimate place of this technique. PMID- 3106650 TI - The membrane-binding domain and myristylation of p60v-src are not essential for stimulation of cell proliferation. AB - Previous studies showed that the amino-terminal domain of Rous sarcoma virus p60v src involved in myristylation and membrane association of the protein is required for morphological transformation and anchorage independence. Analysis of src delection mutants revealed that the amino-terminal one-third of p60v-src, including the membrane-binding domain, is not essential for induction of cell proliferation. These results demonstrated that, in contrast to the cellular target(s) involved in morphological transformation and anchorage independence, the target(s) involved in mitogenic activity is accessible to nonmyristylated src proteins. PMID- 3106653 TI - Bacillus Calmette-Guerin for treatment of superficial transitional cell carcinoma of the bladder in patients who have failed thiotepa and/or mitomycin C. AB - Thirty patients with stage Ta carcinoma in situ or T1 superficial bladder cancer received 6 weeks of intravesical bacillus Calmette-Guerin. All patients had persistent or recurrent tumor despite thiotepa and/or mitomycin C. Response was determined by the results of endoscopy, bladder wash cytology and biopsy performed 4 weeks after the last dose of bacillus Calmette-Guerin. Of the 30 patients 15 (50 per cent) had a complete response. The likelihood of a complete response was better for those with initial Ta lesions (62 per cent) and carcinoma in situ (56 per cent) than for patients with an initial T1 lesion (25 per cent). Although the longest followup is only 36 months (mean 16 months) patients with a complete response have a much better prognosis in terms of subsequent tumor, need for cystectomy and death of bladder cancer. PMID- 3106654 TI - Prostate biopsy after definitive treatment by interstitial 125iodine implant or external beam radiation therapy. AB - The response to definitive radiation therapy of localized carcinoma of the prostate by 125iodine implantation or external beam radiotherapy was monitored by examining specimens from biopsies performed after treatment. We analyzed 126 biopsy specimens obtained 18 months or more after treatment: 71 were obtained from 109 patients treated by 125iodine and 55 from 197 patients treated by external beam radiotherapy. Thereafter, the disease status of these patients was examined at minimum 3-year intervals. No significant statistical difference was found between the negative specimen rates of the 2 treatment modalities: 46 of 71 (65 per cent) after 125iodine implantation and 39 of 55 (71 per cent) after external beam radiotherapy were negative. To analyze the predictive value of biopsy results 103 patients whose prostatic examination results were normal at biopsy or who showed regression of tumor size and tumor induration after radiation were evaluated. The biopsy results from all patients were combined for analysis. Of 77 patients with negative biopsy specimens 16 (21 per cent) have had recurrent disease, compared to 17 of 26 (65 per cent) with positive biopsy specimens (p equals 0.00005). Of the 77 patients with negative biopsy specimens 7 (9 per cent) had local disease recurrence, compared to 12 of 26 (46 per cent) with a positive biopsy specimen (p equals 0.0001). The value of a positive specimen to predict failure remained significant with patients stratified by pre treatment clinical stage and grade of the disease. Our results show that patients with positive specimens from the prostate who had been judged clinically by rectal examination to have responded to radiation therapy had a significantly increased incidence of local and distant failure compared to patients who had negative biopsy specimens. PMID- 3106655 TI - Angiosarcoma of the bladder: a case report. AB - We report a case of angiosarcoma of the bladder. Numerous cases of hemangioma of the bladder have been reported previously but only 3 cases of angiosarcoma have been published. In our case immunoperoxidase staining for factor VIII antigen was useful in substantiating the diagnosis of angiosarcoma. PMID- 3106657 TI - Immunizations, immunoprophylaxis, and chemoprophylaxis to prevent selected infections. US Preventive Services Task Force. PMID- 3106656 TI - Addition of sulfonylurea to insulin treatment in poorly controlled type II diabetes. A double-blind, randomized clinical trial. AB - This study examined the potential beneficial effects of the addition of a second generation sulfonylurea to insulin therapy for poorly controlled type II diabetes. A randomized, double-blind, crossover experimental design was utilized in 16 type II diabetic patients for a period of eight months. Treatment with glyburide, 20 mg/d (plus insulin), compared with placebo (plus insulin) resulted in a significant reduction in mean basal glucose (232 +/- 12 vs 262 +/- 11 mg/dL [12.8 vs 14.4 mmol/L]) and hemoglobin A1C (10.2% +/- 0.5% vs 10.9% +/- 03%) concentrations. Concomitant with this change, basal C-peptide and free insulin values increased with glyburide therapy, but this pharmacological agent did not alter the ability of the patient's erythrocytes to bind insulin. We conclude that in type II diabetic subjects receiving more than 28 units of insulin per day, the addition of glyburide results in a marginal, but statistically significant improvement in basal glucose concentration, but not in glucose tolerance as assessed by integrated glucose concentration. Whether this small improvement in glycemia is worth the additional cost of sulfonylureas or the risk of drug side effects is not known. PMID- 3106659 TI - Serum pepsinogen, a genetic marker in duodenal ulcer. PMID- 3106658 TI - Leads from the MMWR. Enterically transmitted non-A, non-B hepatitis--East Africa. PMID- 3106660 TI - Portal systemic encephalopathy (PSE). PMID- 3106661 TI - Radiometric detection of bacteria. PMID- 3106662 TI - Study of thyroid hormones and TSH levels in patients with hypothyroidism in Karachi. PMID- 3106663 TI - Apolipoprotein A-I and apolipoprotein B in survivors of myocardial infarction. PMID- 3106665 TI - Internal carotid artery aneurysm presenting with severe epistaxis. PMID- 3106664 TI - A study of tuberculosis contacts. PMID- 3106666 TI - Changing pattern of bio and serotypes of vibrio cholerae 01 in rural Bangladesh. PMID- 3106667 TI - Serum ferritin levels in apparently healthy subjects. PMID- 3106668 TI - Free amino acids composition of aqueous humor from Pakistani subjects with senile cataract. PMID- 3106669 TI - Influence of Vitamin C administered after radiation. PMID- 3106670 TI - The protective effect of ascorbic acid on oxytetracycline induced nephrotoxicity and hepatotoxicity. PMID- 3106671 TI - Effect of pyrazinamide on serum and urinary uric acid levels. PMID- 3106672 TI - Autotransfusion in ruptured tubal pregnancy. PMID- 3106673 TI - [The effect of gastrectomy on serum 5-FU concentrations of patients administered UFT per os]. AB - Ten post-total gastrectomy patients and five postsubtotal patients were administered with UFT 3 capsules per os. Then the concentrations of the serums FT 207, 5-FU and Uracil, and that of 5-FU in the lymph-nodes were measured chronologically. The concentration of serum FT-207 reached to its peak one hour after administration of the regimen for both the total and subtotal gastrectomy patients and gradually lowered. The 5-FU serum concentration, on the other hand, showed a rapid drop after reaching a peak one hour after administration of the UFT for both the post-total and subtotal gastrectomy patients. The concentration of 5-FU in the lymph nodes remained five times as high as the serum concentration after four hours for both the post-total and subtotal gastrectomy patients. PMID- 3106674 TI - [An autopsy case of plasmacytoma of the thyroid gland]. AB - An autopsy case of a 75-year-old woman with plasmacytoma of the thyroid gland is presented. There were no toxic symptoms and no abnormal serum protein. On autopsy, a nodule measuring 5.5 X 4.5 X 8 cm was found in the left lobe of the thyroid gland. No myeloma lesions were found in the bone marrow or in other organs. Histologically, the marginal area of the nodule was occupied by typical plasmacytoma, whereas necrotic tissues resembling anaplastic carcinoma were present in the central portion. Chronic thyroiditis was not associated. Immunohistochemically, only the kappa-light chain was demonstrated in the cytoplasm of the tumor cells. PMID- 3106676 TI - [Studies of the pathogenesis of pure red cell aplasia associated with multiple myeloma]. PMID- 3106677 TI - [Treatment of pre-disseminated intravascular coagulation state with gabexate mesilate (FOY)]. PMID- 3106675 TI - [Combined treatment of irradiation and 8 MHz radiofrequency hyperthermia with chemoembolization in advanced renal tumor]. AB - A combined treatment of irradiation and 8 MHz radiofrequency hyperthermia after chemoembolization, using 20 mg of microencapsulated mitomycin C (MMC.mc), was undertaken in a patient with an advanced left renal tumor. The patient, a 70-year old man, noticed a gross hematuria in February, 1984. CT showed a left renal tumor, 88 X 70 mm in size. Histological examination revealed clear cell carcinoma of the left kidney. The tumor was unresectable because of an invasion into the surrounding tissues. Chemoembolization was performed before the combined treatment of irradiation and hyperthermia. He received 23.2 Gy of irradiation and 10 sessions of hyperthermia. Intratumoral temperature reached 42.6 degrees C during the heating. After treatment, there was a tumor regression rate of 58%, as well as pain relief, and an improvement in his appetite loss. He died 8 months after this treatment. An autopsy specimen revealed bionecrotic tumor cells among the prominent necrotic and fibrotic tissues. PMID- 3106678 TI - [Macroglobulinemia with specific skin lesions]. PMID- 3106679 TI - [The stiff-man syndrome]. PMID- 3106681 TI - [Studies on non-A, non-B hepatitis: recent trends]. PMID- 3106680 TI - [Therapy of postoperative hypoxia following mediastinal lymph node excision of esophageal cancer]. PMID- 3106682 TI - [Assistance in home management of central venous hyperalimentation and feeding through a gastric fistula--with special reference to instructions to be given prior to discharge]. PMID- 3106683 TI - Metastatic calcification in the stomach demonstrated by a bone scan in Bence Jones lambda myeloma. AB - A 53-year-old male with Bence Jones lambda myeloma developed hypercalcemia and acute renal failure (calcium 14.4 mg/dl, BUN 40 mg/dl, creatinine 3.0 mg/dl) after initial response to chemotherapy. A 99mTc-MDP bone scan revealed unusual isotope accumulation in the left hypochondrium. Extensive calcium deposition was confirmed in the gastric mucosa in the postmortem examination. Detection of gastric calcification by a bone scan is very rare. Only two cases of gastric calcification visualized on bone scans can be found in the literature, one with multiple myeloma) and one in Hodgkin's disease). PMID- 3106684 TI - Effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS), an immediate precursor of norepinephrine, on the cerebral blood flow in rats. AB - L-threo-3,4-Dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) precursor, 3 mg/kg, i.v., increased the cerebral blood flow (CBF) in both the striatum and hippocampus as well as the mean arterial blood pressure (MABP) in urethane anesthetized rats, as NE infusion did. The L-DOPS induced increase in CBF was inhibited by benserazide (3 mg/kg/hour), a peripheral aromatic L-amino acid decarboxylase inhibitor, and propranolol (3 mg/kg, i.p.), a beta-adrenoceptor blocker as well. These results suggest that the effects of L-DOPS may be attributed to the action of NE formed from L-DOPS, and the action may be mediated by stimulation of beta-adrenoceptor. PMID- 3106685 TI - Enhancement of gastric acid output and mucosal blood flow by tripeptide thyrotropin releasing hormone microinjected into the dorsal motor nucleus of the vagus in rats. AB - Central effect of thyrotropin releasing hormone (TRH) on gastric acid output and mucosal blood flow (MBF) was examined in urethane anesthetized rats. TRH, microinjected into the dorsal vagal complex [the dorsal motor nucleus of the vagus (NDV), the nucleus tractus solitarius and area postrema] induced dose dependent (0.5-50 pmole) increases in gastric acid output and MBF. In contrast, 5 pmole TRH microinjected into various hypothalamic regions had no effect on these gastric parameters. Administration of TRH intraventricularly (i.c.v.) also increased these gastric parameters; however, about a 10 times higher dose of TRH was required to obtain the same order of excitatory effects seen with microinjection to the dorsal vagal complex. Application of anti-TRH serum to the dorsal vagal complex inhibited the increases in gastric acid output and MBF induced by TRH (i.c.v.). The effect of TRH applied to the dorsal vagal complex and i.c.v. were not modified by a concomitant administration of atropine. These results suggests that NDV is probably the site of action of TRH in inducing gastric hyper-functions. The mode of action of TRH seems to be independent of cholinergic muscarinic mechanisms present in the NDV. PMID- 3106686 TI - Inhalation of carbon dioxide enhances the coronary vasodilating action of isosorbide dinitrate in the dog. AB - Two kinds of inspiratory gases, 100% O2 and 81% O2 + 19% CO2, were used for the artificial respiration. Elevating the inspiratory CO2 tension enhanced the decrease in coronary vascular resistance caused by isosorbide dinitrate (100 micrograms/kg), without any change in heart rate and systemic arterial pressure. Such a change in coronary vascular resistance was prevented by indomethacin. The results suggested an interaction between isosorbide dinitrate and CO2, which was mediated by prostaglandins. PMID- 3106687 TI - Pathogenesis of epilepsy in childhood. PMID- 3106688 TI - Functional partial epilepsies in childhood. AB - Out of the 314 children with partial epilepsies below the age of 15 who had been followed for more than 5 years, 122 children with functional partial epilepsies (FPE) were the subjects of this study. The specific modality of interictal EEG findings reminiscent of that of the Rolandic spikes (Dalla Bernardina, 1982, 1984) was compared between functional and organic partial epilepsies. The results were: 1) One hundred and twenty-two patients were found to have FPE out of a total of 314 patients (39%). 2) Fifty-five patients were diagnosed as typical benign epilepsy of children with centro-temporal EEG foci (BECCT) of the 122 functional cases (45%). The remaining 67 patients who defied the diagnostic criteria of BECCT were; 9 cases with frontal EEG focus (7%), 11 cases with central and/or midtemporal EEG foci (9%), 10 cases with occipital EEG focus (8%) and 14 cases with multiple foci (11%). 3) Unfavorable seizure control was observed in cases with frontal foci (44%) and with multiple EEG foci (64%) compared with those whose EEG focus was located in the centro-midtemporal area, (including BECCT; 98%) and in the occipital region (80%). 4) It was noteworthy that the recurrent interictal spikes similar to those of the Rolandic spikes (Dalla Bernardina) were found in more than 50% of the patients not only with functional but with organic partial epilepsies. Our results, at least at the present time, appear to indicate that the recurrent spikes never did signify the benignancy of the seizure prognosis. The importance of differential diagnosis of BECCT from FPE was specifically stressed. PMID- 3106689 TI - Primary generalized epilepsy in adolescence. PMID- 3106690 TI - Application of liposome-entrapped drugs. PMID- 3106691 TI - Demonstration of Akabane virus antigen in experimentally infected mice using immunoperoxidase method. PMID- 3106692 TI - Detection of serum antibody to Leucocytozoon caulleryi in naturally infected chickens by enzyme-linked immunosorbent assay. PMID- 3106694 TI - Role of interleukin-2 (IL-2) and IL-2 receptor expression in the proliferative defect observed in mitogen-stimulated lymphocytes from patients with gliomas. AB - Patients with primary malignant brain tumors manifest, as previously demonstrated, a variety of abnormalities in cell-mediated and humoral immunity. Diminished lymphocyte reactivity has been recently shown in these patients to be linked to deficiencies in interleukin-2 (IL-2) production. In the present study, this observation was expanded by demonstrating that exogenous purified or recombinant IL-2 does not improve the mitogen responsiveness of lymphocytes obtained from these patients. Studies were also conducted to determine the percentage of IL-2-receptor-positive cells at various times after phytohemagglutinin stimulation with the use of anti-TAC monoclonal antibody. The results demonstrated that the number of lymphocytes induced to express receptors for IL-2 was reduced as compared to normal values. These cumulative data therefore suggest that the failure of mitogen to induce blastogenesis in lymphocytes from patients with malignant gliomas results from intrinsic deficiencies in potentially responsive cells, which are expressed in the early phase of the cell cycle. PMID- 3106693 TI - Rearrangement of the c-myc oncogene with heavy-chain immunoglobulin enhancer in tumor DNA from an acute lymphoblastic leukemia patient. AB - The DNA obtained from the leukemia cells of an acute lymphoblastic leukemia (ALL, L3 type) with a pre-B-phenotype and a typical t(8;14) chromosomal translocation showed a rearrangement juxtaposing the c-myc gene and the immunoglobulin (Ig) heavy-chain gene enhancer. This abnormality was only present in the leukemia cells of the patient and correlated with the clinical course of the disease. The breakpoint on chromosome 8 occurred within c-myc intron 1, between 790 and 638 base pairs upstream of c-myc exon 2. This breakpoint position was the nearest to the c-myc exon 2 so far described in Burkitt's type lymphoma-leukemias, and it mapped very near to the location of a major cryptic promoter used by truncated c myc genes. In spite of what was detected in a human lymphoma cell line (Manca) carrying a similar rearrangement, in this case the amount of c-myc transcript was not increased compared to an Epstein-Barr virus-transformed normal lymphoblastoid cell line obtained from the same patient. This may in part be due to the breakpoint position and to the fact that the efficiency of the major cryptic promoter present within the first intron could have been affected by the translocation event. Finally, as previously suggested by others, the phenotype expressed by the leukemia cells supported the notion that this particular type of rearrangement (linking together the c-myc gene and the Ig heavy-chain gene enhancer element) may be associated with a subgroup of B-ALLs showing an immunologic phenotype relatively more immature than that of classical B-ALL. PMID- 3106695 TI - Enhancement of carcinogenesis by the natural anticarcinogen indole-3-carbinol. AB - Indole-3-carbinol (I3C), a natural constituent of cruciferous vegetables, is an inhibitor in several experimental animal models of carcinogenesis by polynuclear aromatic hydrocarbons or aflatoxin B1 (AFB1) when administered prior to or during carcinogen exposure. For assessment of the postinitiation effects of I3C, rainbow trout were exposed to dietary I3C in two different protocols--before and during AFB1 exposure or after AFB1 exposure only. Preinitiation exposure to I3C reduced AFB1-initiated hepatocellular carcinomas in trout as previously reported, but post-initiation I3C exposure strongly enhanced the tumor incidence above the positive AFB1 control. These results reveal the need for additional research to elucidate the overall effect of I3C on chemical carcinogenesis. PMID- 3106696 TI - [Comparative evaluation of the efficacy of nitrosorbide and nitroglycerin in acute myocardial infarct patients]. AB - Intravenous isosorbide dinitrate and nitroglycerin administered within early hours of myocardial infarction have a marked antianginal effect, stabilize the size of necrotic focus and promptly control acute left-ventricular insufficiency. Unlike nitroglycerin, isosorbide dinitrate has a more lasting action and does not affect heart rate and arterial blood pressure. It can therefore be used more extensively in patients with acute myocardial infarction. PMID- 3106697 TI - [Effect of nitroglycerin on hemostasis and the rheologic properties of the blood in acute myocardial infarct]. PMID- 3106698 TI - Fibrillary glomerulonephritis: an entity with unusual immunofluorescence features. AB - We describe seven patients with renal biopsy findings of mild glomerular abnormalities on light microscopy but with prominent accumulation of randomly arranged fibrillar material in the mesangium and capillary walls on electron microscopy. This material differed from amyloid in that fibrils were thicker (diameter range 10 to 19.5 nm) and did not stain with Congo Red. In six of seven cases fluorescence microscopy showed prominent staining for IgG and kappa light chain in mesangium and glomerular capillary walls; in three cases weak lambda chain staining was also present. Stains for IgA, IgM, and lambda chain were otherwise negative. One biopsy showed equal staining for kappa and lambda light chains, but not for heavy chain components. Clinical findings were heterogeneous. Patients presented with features of nephritis and/or nephrotic syndrome. No patient had an associated lymphoplasmacytic disorder, paraproteinemia, or other evidence of systemic disease. On follow-up ranging from five months to 12 years, all patients are still alive; six progressed to end-stage renal disease requiring dialysis. One patient developed recurrent disease in a renal allograft five years after transplantation. Non-amyloidotic fibrillary glomerulonephritis is an ultrastructurally distinct entity of undetermined etiology. The apparent association with monoclonal IgG and kappa light chain deposition observed in this series deserves further study. PMID- 3106699 TI - [Diverticulosis of the appendix]. PMID- 3106700 TI - [Parenteral feeding after operations on the organs of the abdominal cavity]. PMID- 3106701 TI - [Pathogenetic programs of rational parenteral feeding for stomach cancer patients]. PMID- 3106702 TI - [The hyperalimentation of burn patients]. PMID- 3106704 TI - [Parenteral feeding with protein hydrolysates in the combined therapy of burns]. PMID- 3106703 TI - [Treatment of Pseudomonas aeruginosa infection in burn patients]. PMID- 3106705 TI - [Therapy of degenerative maculopathy with Cosaldon A + E]. AB - Results of long-term treatment with Cosaldon A + E in 173 patients (= 345 eyes) exhibiting various stages of degenerative maculopathy are presented (5 tables and 4 figures). Depending on the initial status up to 80% of the treated eyes responded positively to this therapy with only a small side-effect rate: these results suggest that Cosaldon A + E is a promising alternative in the treatment of degenerative maculopathy. PMID- 3106706 TI - [Bilateral complete cryptophthalmos]. AB - A case of bilateral complete cryptophthalmos combined with other malformations is described. The clinical appearance, histology, and the results of computed tomography and electro-ophthalmological investigations are communicated. PMID- 3106707 TI - [Experimental studies of the effect of subconjunctival administration of ascorbic acid on changes in pH, pO2 and pCO2 of the aqueous humor of the rabbit eye after corneal burn with alkaline solution]. PMID- 3106708 TI - [The hypothalamo-hypophyseal thyroid axis, plasma protein concentrations and the hypophyseo-gonadal axis in low T3 syndrome following acute myocardial infarct]. AB - In patients with severely acute diseases, a special relationship of thyroidal hormones with decreased T3 and increased rT3 levels is known, the so-called low T3 syndrome. The aim of this study was to elucidate the involvement of the hypothalamo-pituitary thyroid axis, the pituitary-gonadal axis, the altered hepatic function, the plasma proteins in the low T3 syndrome, and the evaluation of these parameters for prognosis in patients with acute myocardial infarction. Thirty-one patients (29 male, 2 female) with AMI entered the study for the determination of hypothalamo-pituitary thyroid axis and the plasma proteins. Besides routine laboratory determinations, TRH, TSH, T4, T3, rT3, CHE, albumin, total protein, TBG, and estradiol concentrations in plasma were measured daily for 5 days after AMI using immunological and other methods. Twelve male patients with AMI entered the study for the determination of pituitary-gonadal axis; the T3, rT3, estradiol, testosterone, FSH, and LH concentrations in serum were determined using immunological methods. We found that T3 and T4 decreased significantly to a minimum on the first and the second day, respectively, after admission and increased in the course of the observation period. In contrast, rT3 was elevated significantly within the first 2 days and decreased later. TSH and TRH decreased in the first 2 days and increased in the following days. CHE, albumin, and total protein levels significantly showed a minimum on day 4 and TBG significantly showed a minimum on the second day after AMI and increased to day 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106709 TI - Plasma levels of thyrotropin-releasing-hormone in various splanchnic, renal, suprarenal, and cerebral veins. AB - Endogenous TRH levels were determined in plasma obtained selectively via percutaneous transhepatic and femoral catheterization. TRH was measured using a very sensitive RIA method. In the pancreatic veins, internal jugular vein, left testicular vein, and other described veins, normal peripheral levels were found. An involvement of the TRH degrading enzyme (TDE) or a rapid intravasal dilution leading to normal peripheral TRH levels in the veins leaving the brain or pancreas, respectively, is discussed. PMID- 3106710 TI - Pompe's disease in Chinese and prenatal diagnosis by determination of alpha glucosidase activity. AB - We measured the activities of two major forms of alpha-glucosidase in lymphocytes and cultured fibroblasts from normal healthy controls and patients with Pompe's disease by using 4-methylumbelliferyl-alpha-D-glucoside as substrate. We found (1) enzyme activity of the pH 4 and pH 6 forms varied with age, and (2) patients with Pompe's disease showed very low activity of the pH 4 form and a low ratio of pH 4 to pH 6 forms. We established a reference range and were also able to diagnose prenatally the homozygote and heterozygote forms of Pompe's disease which occurred in families of southern Chinese and aborigines in Taiwan. This enzyme biochemical study may be useful in anthropology. PMID- 3106711 TI - Biochemical study of sialidosis type I in a Russian family. AB - A 7-year-old boy from a Russian family with decreased vision and a cherry-red spot but without any somatic and mental abnormalities is described in this paper. The decreased neuraminidase activity in the child's leukocytes and cultured skin fibroblasts and his 10-fold increase in urinary sialyloligosaccharides allowed us to conclude that he was affected by type I sialidosis. Some other results of the biochemical study of this child and his parents are presented. It is the first case of sialidosis in the Russian population. PMID- 3106712 TI - Intracerebral paraventricular hyperdensities: a new CT sign in Krabbe globoid cell leukodystrophy. AB - Computer-assisted tomographic (CT) scanning showed intracranial paraventricular calcification in two out of six patients with enzymatically and/or histologically confirmed Krabbe globoid cell leukodystrophy (GLD) 1-5 months after the onset of symptoms of the disease. PMID- 3106713 TI - Normal dolichol concentration in urine sediments from four patients with neuronal ceroid lipofuscinosis (Batten's disease). AB - The dolichol contents of urine sediments from a patient with infantile (Santavuori), a patient with late infantile (Jansky-Bielschowsky) and two patients with juvenile (Spielmeyer-Vogt) neuronal ceroid lipofuscinosis (Batten's disease) were not elevated when compared to those from healthy controls. PMID- 3106714 TI - Multiple implantation of normal amnion into cattle with generalized glycogenosis type II. AB - One normal and two carrier calves, and two calves affected by generalized glycogenosis type II were given multiple transplants of normal bovine amnion inserted below the external oblique abdominal muscle in the flank. The interval between transplants was approximately 5 months. The amniotic tissue was not acutely rejected but a host versus graft reaction did occur. The level of acid alpha-glucosidase activity in the amniotic tissue fell rapidly but was still present 2 months after transplantation. Enzyme levels in blood or other tissues did not rise. Excess glycogen deposition and muscle damage occurred in the affected calves and appeared to progress at a rate similar to that in untreated affected animals. One of the affected animals died aged 16 months, which was the same age as the longest surviving non-treated animal in our herd. The other treated animal died aged 24 months. PMID- 3106715 TI - Purification and characterization of sialic acid containing materials accumulated in cultured skin fibroblasts from a patient with type II sialidosis. AB - Sialyl conjugates which accumulate in sialidase deficient fibroblasts were made radioactive in the sialic acid moiety by culturing the cells in the presence of [3H]N-acetylmannosamine. The accumulated radioactive compounds were fractionated by anion exchange chromatography and gel filtration. At least nine chromatographically distinct sialyl conjugates were obtained. Neutral and amino sugar analysis of these compounds indicated that all were sialyloligosaccharides of the type which could be derived from glycoproteins containing complex, N asparagine-linked carbohydrate groups. PMID- 3106716 TI - The effect of D-(+)-glucosamine on levels of free N-acetylneuraminic acid and UDP N-acetylhexosamines in infantile sialic acid storage disease (ISSD) fibroblasts. AB - An impairment in the regulation of N-acetylneuraminic acid (NANA) biosynthesis might potentially contribute to accumulation of free NANA in fibroblasts of patients with sialic acid storage disease (ISSD). By the use of a glucosamine loading test an increase in uridine-diphosphate-N-acetyl-hexosamines (UDP-HexNAc) but not in free NANA was found. NANA biosynthesis therefore appears to be under normal regulatory control in ISSD. PMID- 3106717 TI - Comparative use of glucose and fructose in cultured fibroblasts from patients with hereditary fructose intolerance. AB - The utilization of fructose and glucose by fibroblast cultures obtained from patients with hereditary fructose intolerance (HFI) was studied in comparison with fibroblast controls. The cell growth, the time course of D-glucose or D fructose uptake and the consumption of fructose were similar for both HFI and control cells. Some results showed significant differences between these two cell types: HFI cells consumed less glucose, produced less lactate and contained less glycogen than control cells. Furthermore, significantly less [U-14C]D-glucose and [U-14C]D-fructose was incorporated into lipids in HFI cells than in control cells. The mechanisms responsible for these differences observed between the two cell types are not known. PMID- 3106718 TI - Plasma amino acid values and pancreatic beta-cell function in phenylketonuria. AB - In 16 phenylketonuric (PKU) patients aged 5-12 years, plasma glucose, immunoreactive insulin (IRI), C-peptide (CP) and plasma amino acids were measured in basal conditions and under a standard oral glucose tolerance test (OGTT). The beta-cell response to OGTT was higher in PKU patients than in normal subjects as demonstrated by peak levels and areas under the curves of plasma concentrations of IRI and of CP. A significant correlation was observed between plasma phenylalanine values and both IRI and CP 'output' in PKU patients. Mean concentrations of branched chain amino acids and tyrosine in plasma decreased significantly during OGTT, while phenylalanine values increased in PKU subjects. PMID- 3106719 TI - A new family affected by the syndrome of hyperornithinaemia, hyperammonaemia and homocitrullinuria. AB - We have reported three cases of hyperornithinaemia associated with hyperammonaemia and homocitrullinuria (HHH). They deal with two brothers and a sister from a family where the parents and four other children are healthy on clinical and biochemical examination. The biochemical findings in our patients indicate the existence of a defect in the transport of ornithine into the mitochondria. Cultured skin fibroblasts from two of these patients incorporated six times less [14C]ornithine into protein as compared to control cells. The most characteristic sign of the clinical picture is the progressive spastic paraparesis found in one of the cases. Ornithine supplementation and restricted protein intake may be useful in the treatment of this syndrome since after three years of treatment the clinical response was favourable and the patients showed no adverse clinical effects. PMID- 3106720 TI - Arylsulphatase C activity in leukocytes of patients and carriers of X-linked ichthyosis. AB - In Triton X-100 solubilized leukocytes of 17 patients and 8 obligate carriers of X-linked recessive ichthyosis (XLI) the activity of arylsulphatase C (ASC) was determined and expressed as the ratio to beta-galactosidase activity. The ASC/beta-gal ratio of XLI patients is markedly decreased (range 0.07-0.48) in comparison to the corresponding control group of males (range 1.3-2.7). The enzyme ratios of 8 obligate carriers of XLI are decreased (range 0.90-1.9) in comparison to the normal females (2.13-5.52). These results indicate that the determination of the enzyme ratio of ASC/beta-gal in Triton X-100 solubilized leukocytes is a sensitive test for biochemical identification of patients and probably of carriers of XLI. PMID- 3106721 TI - Lethal multiple acyl-CoA dehydrogenation deficiency with dysmorphic features. PMID- 3106722 TI - Control of CO2 lasers during surgery. PMID- 3106724 TI - Stimulation of neomucosal growth by systemic urogastrone. AB - Patching small intestinal defects with colon serosa results in the growth of functional neomucosa. However, the rate of neomucosal growth is slow and the defect contracts markedly. The aim of this study was to determine if systemic urogastrone would enhance neomucosal growth. Twenty-two New Zealand white rabbits had two 2 X 5-cm ileal defects patched with colon serosa and osmotic pumps placed subcutaneously. Eleven animals had saline infused at a rate of 5 microliter/hr. The other eleven rabbits had urogastrone (1 mg/ml saline) infused at the same rate. One animal died in this group. There was a modest increase in neomucosal growth after 2 weeks of urogastrone infusion. Three weeks after patching, defect coverage was significantly greater in the urogastrone group (99.8 +/- 0.1 vs 96.0 +/- 1.2%, P less than 0.005) and more defects were completely covered by neomucosa (6/10 vs 1/12, P less than 0.05). Less contraction occurred in the urogastrone group (46 +/- 2 vs 35 +/- 3% initial defect, P less than 0.005) and resultant neomucosal surface area was greater (361 +/- 12 vs 266 +/- 20 mm2, P less than 0.0005). In vitro glucose uptake was significantly greater in the urogastrone group but disaccharidase and diamine oxidase activity were similar. Crypt cell production rate was significantly greater 2 weeks after operation compared to 3 weeks in both groups and was greater in the urogastrone group compared to the saline group at 2 weeks (24.9 +/- 1.1 vs 20.1 +/- 1.1, P less than 0.02). Systemic urogastrone enhances neomucosal growth by increasing the rate of growth and diminishing contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106723 TI - Intraperitoneal nutritional support: initial results in a canine model. AB - To evaluate the capacity of the peritoneal membrane to efficiently absorb complex nutritional solutions, five adult mongrel dogs were prepared with peritoneal and intravenous catheters. In duplicate studies each dog's peritoneal catheter was rapidly infused with 1 liter of fluid containing 1.25% glucose, 5% fat emulsion, 2.5% mixed amino acids, and 20 ml of standard electrolyte additive solution. Plasma and peritoneal fluid nutrient and electrolyte concentrations and osmolarities were measured initially, 1/2 hr, and hourly for 5 hr after infusion. Mean peritoneal fluid volume increase was 56 +/- 45 ml at 5 hr (P less than 0.05). Plasma osmolarity remained unchanged as peritoneal fluid osmolarity rapidly declined to plasma level over the initial 2 hr. Peritoneal fluid concentrations of glucose, triglycerides, and amino acids all fell precipitously during the first hour (P less than 0.01) while plasma concentrations rose in reciprocal fashion (P less than 0.01). Maximal rises above basal plasma concentrations all occurred at 1/2 hr and amounted to 42.7% for glucose, 39.7% for triglycerides, and 113.2% for amino acids. Levels returned to normal or near normal by 5 hr. Net absorption of glucose was 91.7% of the total glucose load after 5 hr of intraperitoneal dwell time. Triglyceride absorption was 65.1% and amino acid absorption was 91.9%. Greater than 75% of total nutrient absorption occurred during the initial hour of dwell. It is estimated that both nonprotein energy and nitrogen requirements could be met with two to three intraperitoneal nutrient solution exchanges per day. Thus, provision of total nutritional needs may be possible with an intraperitoneal support system. PMID- 3106725 TI - Mastectomies for malignancy: a DRG-based hospital utilization analysis. AB - The study identified hospital utilization patterns by diagnosis-related group (DRG) produced by mastectomies for malignancy in Sacramento, California, and Syracuse, New York, for the years 1981-1984. A total of 3,449 discharges were included. Total and subtotal mastectomy discharges per capita increased in both areas. The proportion of mastectomy discharges attributed to total mastectomies increased in Sacramento and decreased in Syracuse. Mean stays for mastectomy DRGs declined by 13.72 to 56.38%. In 1984 mean stays ranged from 4.79 to 7.49 days for total mastectomies and 1.88 to 5.44 days for subtotal mastectomies. A major problem identified by the study was the lack of DRG sensitivity to differences in types of procedures. Under DRGs, radical and simple mastectomies are combined in one type of category, while subtotal mastectomies, quadrant resections, and breast biopsies are combined in another. PMID- 3106726 TI - Influence of phlebotomy treatment on abnormal hypothalamic-pituitary function in genetic hemochromatosis. AB - To test the hypothesis that deficiencies in hypothalamic-pituitary function in genetic hemochromatosis result from cellular injury by iron deposits, we conducted provocative tests in 11 men with genetic hemochromatosis before and after iron depletion by serial phlebotomy and in 10 control subjects. We gave combination intravenous injections of insulin (0.15 U/kg), luteinizing hormone releasing hormone (LHRH, 100 micrograms), and thyrotropin releasing hormone (400 micrograms) and then measured plasma glucose, growth hormone, corticosteroids, follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid stimulating hormone at 30-minute intervals for 90 minutes. Phlebotomy caused a substantial decrease in median values for serum ferritin, deferoxamine-chelatable iron, and hepatic iron concentration. Before phlebotomy, stimulation by hypoglycemia and thyrotropin releasing hormone caused significantly less secretion of growth hormone (P = 0.004) and prolactin (P = 0.03) in patients than in control subjects. No significant improvement was noted, however, in growth hormone or prolactin secretion after phlebotomy. Of the 11 patients, 7 had secondary hypogonadism, and phlebotomy did not improve the serum testosterone, follicle-stimulating hormone, luteinizing hormone, or responses to LHRH in any case. Chlorpromazine injections failed to elevate serum prolactin in all patients, and administration of levodopa caused a partial reduction in serum prolactin; thus, the hypothalamus may be an important locus of endocrine malfunction in these patients. We conclude that abnormal hypothalamic-pituitary function in genetic hemochromatosis is not substantially improved by iron depletion therapy. PMID- 3106727 TI - Effects of development and ageing on pulmonary NADPH-cytochrome c reductase, glutathione peroxidase, glutathione reductase and thioredoxin reductase activities in male and female rats. AB - The behaviour of the principal NADPH-consuming detoxification enzymes (NADPH cytochrome c reductase, glutathione peroxidase-glutathione reductase system, and thioredoxin reductase) was studied during development and senescence of the rat lung. We have also studied the influence of sex on the development and senescent values. The NADPH-cytochrome c reductase activity increases at birth and afterwards remains constant until the 25th day after birth, at which age there is a maximum activity. Its activity decreases during the ageing period in both sexes. The glutathione reductase and thioredoxin reductase activities show significant differences with respect to sex during the adult stage, however during ageing these differences disappear. These enzymes show maximum activity at 25 days after birth, and afterwards the activity decreases continuously until the adult levels are reached. The activity of glutathione reductase is increased during the ageing period, especially in the female rats, however, in senescence the levels of thioredoxin reductase are lower than in the adult stage. The glutathione peroxidase shows a significant difference between both sexes during senescence and in the male its activity in this stage is higher than during development and adulthood. PMID- 3106728 TI - [Gonococci as producers of beta-lactamase in Catalonia]. PMID- 3106729 TI - Nutritional aspects of preoperative management. AB - The preoperative evaluation of the surgical patient should include a careful evaluation of the patient's nutritional status. A careful history and physical examination are appropriate and reliable means for evaluation of nutritional status. Patients with certain diagnoses, such as Crohn's disease or visceral malignancies, are likely to become malnourished even if they are not malnourished at the time of hospital admission. Preoperative and postoperative nutritional support, continued until the patient is able to take adequate nutrients by mouth, is an important part of the management of these patients and can improve the care and decrease the likelihood of complications. PMID- 3106730 TI - Protective effect of triflusal and acetylsalicylic acid against arachidonic acid induced cerebrovascular occlusion in anesthetized rats. AB - Within 60 sec after intracarotid injection of 0.33 mg/kg arachidonic acid, a pronounced attenuation of electrocortical activity, approaching electrocerebral silence, was induced in the ipsilateral hemisphere of anesthetized and heparinized rats. This effect was a consequence of the cerebrovascular occlusion due to platelet aggregates induced by arachidonic acid. This model has been used to evaluate the protective effect of acetylsalicylic acid (ASA) and of triflusal 2 hr after a single oral dose of 50 mg/kg or after 50 mg/kg, for 5 days. Pentylenetetrazol at 10 mg/kg, i.v. exerts a stimulant effect on CNS, and was used as a positive control. ASA and triflusal exhibit a protective effect in about 35% of animals when acutely administered. After chronic treatments (5 days), the effect of triflusal (60% protection) was superior to that of ASA (27% protection) (p less than 0.01). PMID- 3106731 TI - [Therapy of allergic rhinitis in childhood]. AB - Allergic rhinitis is the most common of all allergic disorders. After summarising the clinical features and diagnostic approach with regard to differential diagnosis, we will discuss the therapeutic modalities. As with all long-term therapy measures, it is essential to persuade both the child and the parents to participate in the treatment and to get their co-operation. PMID- 3106732 TI - Characteristics of human T-cell clones from BCG and killed M. leprae vaccinated subjects and tuberculosis patients. Recognition of recombinant mycobacterial antigens. PMID- 3106733 TI - Peptides as potential immunodiagnostic reagents to detect mycobacterial infections. PMID- 3106734 TI - Analysis of a leprosy-specific antibody epitope. PMID- 3106735 TI - Immunogenic synthetic peptides against mycobacteria of potential immunodiagnostic and immunoprophylactic value. PMID- 3106736 TI - Lepromin stimulates interleukin-2 production and interleukin-2 receptor expression in situ in lepromatous leprosy patients. PMID- 3106737 TI - Regulation of cell-mediated immunity in lepromatous leprosy. PMID- 3106738 TI - Attempts to assess the contribution of T lymphocytes from the L3T4+ and LYT2+ subsets in the immunological control of cutaneous leishmaniasis. PMID- 3106739 TI - Effects of lithium on the pituitary-gonadal axis in the rat: evidence for dose dependent changes in plasma gonadotropin and testosterone levels. AB - The purpose of the present study was to examine the effects of lithium, a drug which is now used rather widely in the treatment of acute mania and the prophylaxis of manic-depressive bipolar disorders, on the pituitary-gonadal function in the laboratory rat. Sexually adult male rats, maintained under standardized laboratory conditions (LD 14: 10; lights on at 06:00 h, CST), were injected (ip) with lithium chloride both acutely for 1 day and chronically for 5 days, and by utilizing a low and high dose. For the low dose, lithium was injected twice daily (at 10:00 and 15:00 h) at 2.5 meg/Kg for 1 and 5 days, whereas in the high dose groups, also receiving lithium twice daily and at the same hours, the dosages were 5 meq/Kg for 1 day and 3.5 meq/Kg for 5 days. Animals were sacrificed 4 hours after the last lithium (or saline) injections. Plasma and pituitary levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and plasma levels of testosterone (T) were measured by radioimmunoassay (RIA). The administration of the low dose led to a significantly higher (P less than 0.001) plasma FSH, but unaltered plasma LH, levels after 5 days. In contrast, the high dose lithium led to significant suppressions of plasma LH (P less than 0.02; on day 5) and FSH (P less than 0.001; on both day 1 and 5) levels. The levels of plasma T also showed a significant reduction following the low dose (P less than 0.02; on day 5), as well as the high dose lithium treatment, as evident after both 1 (P less than 0.02) and 5 (P less than 0.02) days. Regardless of the dosage, or the duration of treatment, pituitary gonadotropin levels remained unaltered following lithium. The results of our present experiments suggest that lithium administration, either acutely or on a chronic basis, might be associated with significant adverse effects on the pituitary-testicular axis. Furthermore, since some of the hormonal changes were evident when plasma lithium concentration was within the therapeutic range, our data may have potential clinical implications. PMID- 3106740 TI - Effects of parenteral nutrition with high doses of linoleate on the developing human liver and brain. AB - The developmental changes in the fatty acid composition of ethanolamine phosphoglycerides (EPG) and choline phosphoglycerides (CPG) were studied in the liver and brain of 18 newborn infants with gestational ages ranging from 20 to 44 wk. A small group of five newborns receiving total parenteral nutrition (TPN) with high doses of linoleic acid (18:2 omega 6) was also studied and compared to controls of the same gestational age to look for effects on the developmental fatty acid patterns of liver and brain EPG and CPG. TPN with Intralipid 20% was given for 4-12 days, the total fat intake being 14.7-90 g (mean +/- S.D. = 47.1 +/- 29.8 g). The main developmental changes in the liver and brain of the control group were an increase in 22:6 omega 3 (docosahexaenoic acid) at the end of gestation and a linear decrease in 20:4 omega 6 (arachidonic acid) and 18:1 omega 9 (oleic acid) in EPG and CPG. A very good correlation in the percent values of these fatty acids in the brain and liver tissues was obtained. Very significant changes in the fatty acid composition of liver EPG and CPG could be found in the infants receiving TPN with Intralipid-mainly an increase in 18:2 omega 6, a decrease in the linoleate elongation/desaturation to longer members of the series and a decrease in the 22:6 omega 3 levels of liver EPG and CPG. In the brain, only an increase in the 18:2 omega 6 value of CPG, not accompanied by any increase in the longer omega 6 fatty acids, could be detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106741 TI - Role of the lymphatic system in the transport of absorbed 7,12 dimethylbenzanthracene in the rat. AB - To determine the role of the intestinal lymphatic system in the absorption of a polycyclic aromatic hydrocarbon, 7,12-dimethylbenzanthracene, a radiolabeled preparation of the compound was given by intraduodenal infusion to rats in doses of 10 micrograms, 10 mg and 20 mg in olive oil solution. The hydrocarbon appeared to be absorbed from the intestine in a fractional manner, ca. 20% of the administered radioactivity being recovered totally in bile and intestinal lymph in 24 hr at all three dose levels. Biliary radiolabel accounted for 75-82% of combined recovery of radioactivity in bile and lymph with all three doses. The recovery of significant amounts of radiolabel in bile before the appearance of isotope in lymph, together with the fact that the biliary radiolabel greatly exceeded at all times the lymphatic recovery of isotope, suggests that an alternative pathway, presumably the portal venous route, is of major importance in the transport of the absorbed hydrocarbon. PMID- 3106742 TI - Lack of hepatitis B virus DNA sequences in sera from patients with acute and chronic liver diseases diagnosed as non-A, non-B-hepatitis. AB - The sera of 15 individuals with transfusion-associated acute or chronic non A, non B hepatitis, which lacked hepatitis B virus markers, were tested for hepatitis B virus DNA by dot blot hybridization test. Three sera of two patients positive in this test, however, also gave positive results when the labeled plasmid was used as probe instead of labeled HBV-DNA, indicating false positive results in the initial test. In conclusion, the data indicated that sera of patients with confirmed non A, non B hepatitis do not contain DNA-sequences in the serum hybridizing with HBV-DNA. PMID- 3106744 TI - [Specific anti-Trypanosoma cruzi antibodies in children with acute Chagas' disease]. PMID- 3106745 TI - [Chagas' disease in dogs experimentally infected with Trypanosoma cruzi]. PMID- 3106743 TI - The fate of electron opaque tracers (horseradish peroxidase and lanthanum chloride) during valproic acid-induced choleresis. AB - Horseradish peroxidase (HRP) and lanthanum chloride (LaCl3) are useful tools for, respectively, the study of vesicular transport through the hepatocyte and the study of the permeability of junctional complexes. These tracers have been used to detect the changes associated with the choleresis independent of bile acids induced by valproic acid (VPA) in rats. The animals were given a single dose of VPA (600 mg/kg, ip). HRP (100 mg/kg) or 5 mM LaCl3 were given intraportally after 1 h, when bile flow had increased twofold. The excretion of HRP in bile was measured colorimetrically up to 2 h after HRP. Ultrastructural morphometry was conducted on liver of intact rats taken from 1 to 40 min after HRP. The volume density (VD) of HRP-containing vesicles and of HRP-containing multivesicular bodies (MVB) was counted. In VPA-treated rats, HRP appeared in bile with a peak showing at 5 min against 20 min in controls, but the total amount of HRP excreted was less than in controls. The intrahepatocytic vesicular transport of HRP was also modified, showing a peak at 3 min in VPA-treated rats compared to 10 min in controls, together with a decreased VD of pericanalicular vesicles. This was accompanied by an increase of HRP-containing MVB, already evident at 5 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3106746 TI - [Immunoglobulin E and Chagas' disease]. PMID- 3106747 TI - [Chronic active hepatitis]. PMID- 3106748 TI - Humoral antibody response in mice infected with Trypanosoma cruzi. PMID- 3106749 TI - Serious infections caused by Bacillus species. AB - Thirty-eight patients with serious infections caused by organisms belonging to the genus Bacillus are described. Our experience, and that reported in the literature, indicates that, in most cases, isolated Bacillus bacteremia is not a particularly serious disease. Therefore, under most circumstances, empiric antibiotic therapy designed specifically for treatment of Bacillus is probably not necessary. Endocarditis can occur, but apparently follows bacteremia only infrequently. When these bacteria cause localized infection such as pneumonia, pan-ophthalmitis, visceral abscess, or musculoskeletal infections, tissue necrosis and profound morbidity are the rule. The frequency of these complications following bacteremia appears to be low but cannot be estimated from our experience or that reported in the literature reviewed. The role of intravascular devices and trauma as predisposing factors is emphasized. Immunocompromised hosts and intravenous drug abusers appear predisposed, but intravascular devices in the former group may play an important role in the pathogenesis of Bacillus infections. Antibiotics which appear especially useful in the treatment of Bacillus infections are clindamycin and vancomycin, to which the vast majority of strains are susceptible in vitro. Beta-lactam antibiotics, including the new cephalosporins and penicillins, are of little value in this setting. PMID- 3106750 TI - [Problems in acute therapy of coronary heart disease using drugs that reduce preload and afterload]. PMID- 3106751 TI - [Problems in long-term therapy of coronary heart disease: clinical aspects]. PMID- 3106752 TI - [Problems in long-term therapy of coronary heart disease: pharmacotherapy]. PMID- 3106754 TI - The contribution of small gut to the 3-methylhistidine metabolism in the adult rat. AB - Twenty male adult Sprague-Dawley rats received parenteral nutrition following a duodenoileostomy which left only 8% to 10% of the small gut intact. On the first postoperative day, the urinary 3-methylhistidine (3-MH) excretion rose to 1.5 to 1.7 times the preoperative level but fell again within 12 to 14 days to the basal level. A control group of 10 rats with small gut anastomosis without resection yielded similar results. We conclude that, at least in rats, the small intestine does not make a significant contribution to 24-hour urinary excretion of 3-MH. The transient postoperative rise in 3-MH excretion is probably due to postinjury metabolism. PMID- 3106753 TI - [Comparative biological characterization of Berenice and Berenice-78 strains of Trypanosoma cruzi isolated from the same patient at different times]. AB - The Berenice-78 strain of T. cruzi is very different from the Berenice strain isolated 16 years earlier from the same patient. The authors verified its high infectivity and low virulence for C3H inbred mice that survived the acute phase of infection. In these animals, it was verified that the tropism of parasites was more accentuated for cardiac and skeletal musculature and the parasitaemic level progressively increased with successive blood passages with posterior stability. In relation to Berenice strain the same characteristics were observed as described by Brener, Chiari & Alvarenga (1974). The increase in its virulence for albino mice was again demonstrated. The authors discussed the possibility of reinfection of the patient called Berenice and the importance of knowledge about T. cruzi strains of low virulence for laboratory animals. PMID- 3106755 TI - Effects of sauna and glucose intake on TSH and thyroid hormone levels in plasma of euthyroid subjects. AB - The effect of sauna on thyroid function parameters and its modification by glucose was studied in young euthyroid male volunteers. A 30-minute stay in sauna resulted in an increase in plasma TSH; the response was exaggerated if glycemia had been increased by oral glucose intake at the beginning of the experiment. Plasma rT3 also increased in sauna, this response was, however, blunted by the higher glycemia. TSH response to sauna was definitely present in young men (aged 20 to 25) and absent in middle-aged ones (50 to 55). To explore the mechanism of the effect of increased glycemia, TRH tests were performed and dopamine infusions were administered with and without glucose pretreatment. Increased glycemia did not affect TSH and T3 response to TRH in young volunteers; however, 90 minutes after the administration, plasma rT3 levels were significantly lower in glucose pretreated subjects than in those receiving TRH injections after water pretreatment. Simultaneous infusion of glucose prevented the inhibitory effect of dopamine infusion on plasma TSH. It was concluded that glucose directly modulates the effect of sauna on plasma TSH at a suprapituitary level, while the inhibiting effect of glucose on plasma rT3 response to sauna and TRH is probably mediated by the insulin effect on thyroid hormone metabolism. PMID- 3106756 TI - Effects of CS-514 on serum lipoprotein lipid and apolipoprotein levels in patients with familial hypercholesterolemia. AB - Effects of CS-514, a new competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum lipoprotein lipid and apolipoprotein levels were studied in 13 heterozygous patients with familial hypercholesterolemia. Treatment with 10 mg of CS-514 twice daily reduced total serum cholesterol, low-density lipoprotein (LDL), and intermediate-density lipoprotein (IDL) cholesterol levels by 25%, 33%, and 33%, respectively, and increased high-density lipoprotein (HDL) cholesterol levels by 15%. Apolipoprotein B, E, and C-II levels decreased by 24%, 20%, and 19%, and apolipoproteins A-I and A-II levels increased by 10% and 7%, respectively. One patient showed abnormally high levels of SGOT, SGPT, and serum alkaline phosphatase, which returned to normal levels immediately after the cessation of CS-514. No other adverse effects were observed. Thus, CS-514 reduces atherogenic lipoproteins and apolipoprotein B, and increases HDL and apolipoprotein A-I and A-II, and appears to be a useful drug for heterozygous familial hypercholesterolemia. PMID- 3106757 TI - Effects of two new aldose reductase inhibitors, AL-1567 and AL-1576, in diabetic rats. AB - Two new potent aldose reductase inhibitors, AL-1567 (DL-spiro(2-fluoro-9H-fluoren 9,4'-imidazolidine)-2',5'-dione) and AL-1576 (spiro-(2,7-difluoro-9H-fluoren-9,4' imidazolidine)2',5'-dione), have been characterized with respect to in vitro activity toward rat lens and human placental aldose reductase and in vivo activity in uncontrolled, severely diabetic rats dosed acutely with the compounds. The IC50 values for inhibition of rat lens aldose reductase are 2.7 X 10(-8) mol/L for AL-1567 and 8.5 X 10(-9) mol/L for AL-1576; very similar IC50 values were measured for each compound with the human placental enzyme. When the compounds were administered orally once per day to 3-week diabetic rats for a period of eight days, the ED50 values for normalization of lens sorbitol levels were 0.60 mg/kg for AL-1567 and 0.05 mg/kg for AL-1576, and for normalization of sciatic nerve sorbitol levels; 0.22 mg/kg for AL-1567 and 0.04 mg/kg for AL-1576. Compared with published data on other aldose reductase inhibitors evaluated in very similar diabetic rat models, both compounds have unusually high activity in lens, and AL-1576 appears to be the most active such compound in both lens and sciatic nerve reported thus far. The evidence linking increased sorbitol pathway activity to diabetic complications, such as cataract and neuropathy in animal models, suggests that aldose reductase inhibitors will be useful therapeutic agents in human diabetics. PMID- 3106758 TI - Endometrium and plasma hormone profile in the peri-menopause and post-menopause. AB - Endometrial histology and plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 beta-oestradiol (E2), oestrone (E1) and progesterone (P) were studied in 483 women over a period of 13 yr (6 yr before and 7 yr after the start of definitive amenorrhoea, defined as the last menstrual bleeding). The patterns for these parameters were established on the basis of the results of 1227 gonadotrophin and steroid determinations and 721 endometrial biopsies. Three periods were identified. During the first, from year-6 to year-3, gonadotrophin levels increased gradually, while those of E2 remained normal, with peaks in some cases. Mean plasma P levels were within the normal range until year-3, but they then decreased progressively. Endometrial histology was similar to that observed during reproductive life. In the second period, from year-3 to year+1, there was a concomitant rise in gonadotrophins as the E2 and P levels decreased. However, at the start of definitive amenorrhoea, the mean E2 and P levels fluctuated between 60 and 100 pg/ml and between 2 and 3 ng/ml, respectively. The endometrium reflected this decrease in E2 and P production. It was not atrophic but proliferative when definitive amenorrhoea commenced. During the last period, from year+1 to year+7, gonadotrophins reached a plateau at high levels, while those of E2 continued to fall, reaching very low values at year+4, after which they reached a plateau. P levels were at the detection limit of the technique. The correlations between all plasma steroid levels and endometrial histology demonstrated discrepancies in 30% of cases: proliferative or hyperplastic endometria were seen at E2 levels of under 60 mg/ml, atrophic endometric at E2 levels of over 60 pg/ml and secretory endometria at very low P levels. PMID- 3106759 TI - Occurrence of antipseudomonal beta-lactams and aminoglycosides resistance in Pseudomonas aeruginosa during therapy. AB - Four strains of Pseudomonas aeruginosa clinical isolates were studied for resistance to antipseudomonal beta-lactams and aminoglycosides. Two of these strains were isolated from two different patients before antibiotic treatment, the other two strains, isolated during therapy, developed resistance to many of antipseudomonal beta-lactams and, in addition, to aminoglycoside antibiotics. All the strains produced a constitutive chromosomal beta-lactamase, while the latter two showed a significant reduction in permeability coefficient. Thus, a permeability change may be the major factor involved in the resistance to most antipseudomonal beta-lactams and may be responsible for development of cross resistance to aminoglycosides. PMID- 3106760 TI - Surveillance of meningococcal meningitis in the Latium region, Italy 1984-1985. AB - A surveillance system on meningococcal meningitis was set up in an Italian region in 1984, to monitor the trend and distribution of the disease, to acquire bacteriological data, to evaluate control measures. Results of the first two years show no overall increase in the incidence of the disease, on the other hand an increased incidence in the 15-24 age group, a high fatality rate, a prevalence of serogroup C and serotype 2a and widespread resistance to sulfonamides were observed. Features characteristic of an epidemic period are thus present in the context of an endemic setting. PMID- 3106761 TI - Dimerization of 2,6-dimethoxyphenol by Aspergillus flavus: evidence for the reaction occurring close to mycelia. AB - Aspergillus flavus grown on 2,6-dimethoxyphenol as sole carbon source produced tetramethoxy-p-dibenzoquinone by a free radical mechanism. The product was identified by H-nmr and ms. Scanning electron microscopy and light microscopy were used to follow the growth of mycelia and the attachment of crystals to the mycelial surfaces. Formation of dimer was inhibited by the presence of glucose in the medium. PMID- 3106762 TI - Planned pregnancy in a patient who was receiving home parenteral nutrition. AB - A planned pregnancy with a satisfactory outcome is reported in a 33-year-old woman who had received long-term home parenteral nutrition after a massive volvulus, with resection of almost the entire small intestine, six years previously. No obstetric complications were observed and a normal baby girl was delivered by caesarean section. The only nutritional complication that was encountered was aching pain in the limbs and weakness at 20 weeks' gestation, which was due possibly to calcium deficiency and/or the metabolic bone disease that is peculiar to long-term parenteral nutrition and to other unidentified nutrient deficiencies. PMID- 3106763 TI - [Taxonomic position of so-called small mites of medical and veterinary significance]. PMID- 3106764 TI - [Post-traumatic necrosis of the tongue]. PMID- 3106765 TI - [Submergence of dental roots under the alveolar mucosa. Review of the literature]. PMID- 3106766 TI - [Dentin adhesive compound in Black's class V cavities treated with different detergents]. PMID- 3106767 TI - Reimbursement resistance to treatment and support for the long-term mental patient. PMID- 3106768 TI - Tuberculosis control among homeless populations. PMID- 3106769 TI - Treatment and perceived blood pressure control among self-reported hypertensives- Behavioral Risk Factor Surveillance System, 1986. PMID- 3106770 TI - Mortality due to conditions preventable by medical intervention--New Hampshire, 1970-1985. PMID- 3106771 TI - Bicycle-related injuries: data from the National Electronic Injury Surveillance System. PMID- 3106772 TI - Trends in human immunodeficiency virus infection among civilian applicants for military service--United States, October 1985-December 1986. PMID- 3106773 TI - Organic solvents in the workplace. PMID- 3106775 TI - Deaths among the homeless--Atlanta, Georgia. PMID- 3106774 TI - Update: human immunodeficiency virus infections in health-care workers exposed to blood of infected patients. PMID- 3106776 TI - Measles--United States, 1986. PMID- 3106777 TI - Human immunodeficiency virus infection transmitted from an organ donor screened for HIV antibody--North Carolina. PMID- 3106778 TI - Rocky Mountain spotted fever--United States, 1986. PMID- 3106779 TI - Premature mortality due to cerebrovascular disease--United States, 1983. PMID- 3106780 TI - Recreational boating fatalities--Ohio, 1983-1986. PMID- 3106781 TI - Update: Creutzfeldt-Jakob disease in a patient receiving a cadaveric dura mater graft. PMID- 3106782 TI - Potential increased demand for lead testing as a result of recent HUD regulations. PMID- 3106783 TI - Tuberculosis among Asians/Pacific Islanders--United States, 1985. PMID- 3106784 TI - [Study on perigastric lymphatics using 111In-oxine-labeled lymphocytes]. PMID- 3106785 TI - [Effects of the combination of glucose, fructose and xylitol as carbohydrates with branched-chain enriched amino-acids on postoperative total parenteral nutrition of esophageal cancer patients]. PMID- 3106786 TI - Immunological localization of the GTP-binding protein Go in different tissues of vertebrates and invertebrates. AB - Bovine brain contains two GTP-binding proteins, Gi and Go, which are substrates for ADP ribosylation by pertussis toxin. The Gi protein mediates hormone and GTP inhibition of adenylate cyclase, but the function and the precise tissue distribution of Go are unknown. To immunologically probe the localization of Go, we have purified the Go alpha and G beta, gamma subunits of Go and have raised antibodies against them. The polyclonal anti-Go alpha antibodies obtained were very selective for Go alpha compared to Gi alpha or Gs alpha. The positive Go alpha and G beta, gamma immunoreactivities were investigated in different tissues of vertebrates and invertebrates on immunoblots after gel electrophoresis of the crude membranes. The anti-G beta, gamma antibodies recognized a 35-36-kDa protein in brain of vertebrates such as mammals (rat), avians (pigeon), amphibians (frog), fish (trout), and reptiles (turtle) but not in the invertebrates such as molluscs (snail) and insects (locust). With the anti-Go alpha antibodies a high level of immunoreactivity was detected at molecular weights of 39,000-40,000 in the brain of invertebrates as well as in the central nervous system of vertebrates. Moreover, ADP ribosylation with pertussis toxin occurred in the nervous system of invertebrates. These results suggest that the GTP-binding proteins of invertebrates either are devoid of G beta, gamma subunit or, more probably, possess immunologically different G beta, gamma subunits when compared to those of vertebrates. In the vertebrates, Go alpha immunoreactivity was also present in the peripheral nervous system in areas such as the superior cervical ganglia and sciatic nerve. When examined with the anti-Go alpha antibodies, the neuro-and adenohypophysis exhibited a similar immunoreactivity which was about 6 times lower than in brain. Our antibodies also recognized a 40-kDa protein in human adipocytes but at a concentration 17 times lower than that recognized in brain. Taken together, these data show that the Go alpha subunit is well conserved through evolution and, furthermore, confirm that Go alpha is not strictly limited to the nervous system. This suggests that the protein Go ensures a function required for neuronal activity but also present in some other non nervous tissues. PMID- 3106787 TI - [Allelic exclusion in hybridomas. II. Characteristics of the synthesis of 2 allelic variants of rat immunoglobulin kappa-chains in a cloned hybridoma line]. AB - Production of Igk-1a and Igk-1b allelic variants of rat Ig kappa-chains in hybridoma clone 4C2 was studied. Gel-filtration of the culture fluid demonstrates that the cells secrete isolated L-chains in monomeric and dimeric form. Different L-chain allotypes fail to associate in dimers. Immunofluorescence studies prove that both allelic variants are produced in a single cell. Cells with double allotype production loose the ability to produce one or both allotypes at an essentially heightened rate as compared to those producing Igk-1a or Igk-1b alone. The results fit well into the regulated allelic exclusion model. PMID- 3106789 TI - [Growth hormone secretion following administration of growth hormone releasing hormone in constitutional short stature and idiopathic growth hormone deficiency]. AB - A stimulation test using 1 microgram growth-hormone-releasing factor (GRF 1-29 X NH2)/kg bodyweight was performed in children with familial short stature and in children with constitutional delay of growth and development. The GH secretion induced by this means was not different in these groups, but there was a difference in the response between normal children and children with idiopathic growth hormone deficiency (GHD). GH secretion after GRF administration was significantly lower in the GHD group than in the other groups. However, 6 of 24 patients with GHD responded to the test with a normal increase in GH (greater than 10 ng/ml), and 11 with an intermediate response (2-10 ng/ml). Thus, the test does not differentiate individual patients with defective growth hormone secretion from normal short children. PMID- 3106788 TI - [Selective interaction of immunoglobulin polypeptide chains. Quantitative evaluation of the idiotypic and antigen binding activity of reassociated immunoglobulin molecules]. AB - We have analysed reassociated Ig molecules, containing heavy (H) or light (L) chains of Ig-B2 monoclonal antibody with human fibronectin binding activity and L of H chains of normal mouse serum immunoglobulin (Ig-NM). Examination of Ig-B2 idiotype expression in reassociated Ig indicated that 0.4% L-NM and 0.8% H-NM were able to restore Ig-B2 idiotype. The analysis of antigen binding capacity of reassociated Ig demonstrated, that only 4% H-NM created antigen binding site in complex with L-B2. We have determined the leading role of L-chain in creation of idiotype and binding site of Ig-B2. Selectivity of interaction between H and L chains is discussed. The results indicate, that not more than 4-6% of random H--L combinations produce functional Ig. PMID- 3106790 TI - [Spectrum of post-enteritic reactive arthritis in childhood]. AB - Eleven children (7 boys and 4 girls) suffered from reactive arthropathies following an enteritis. Mean age at onset of disease was 9.7 years (range 3.3 14.5 years). Six children had a classical Reiter's syndrome and two a juvenile spondyloarthritis diagnosed earlier. In 10/11 children, onset of disease was within 5 weeks following a febrile enteritis. The enteritis was confirmed in all 6 cases examined during the first three months after onset of disease. The arthritis was predominantly oligoarticular and affected mostly the joints of the lower extremities and toes. Recurrent enthesopathies and arthralgias occurred in most children. HLA-B27 was positive in 9 (82%). During a follow-up of 0.9 to 6.7 years, arthritis relapsed in most of the patients and 4 children had severe arthritis, and 5 sacroiliitis. Urethritis and occular signs relapsed frequently, but there were no noticeable disabilities. Two other girls had self-limited arthralgia and erythema nodosum following a febrile enteritis. This disease may represent the first stage of the broad clinical spectrum of the reactive arthropathies. In our outpatient clinic of paediatric rheumatology, 9% of 127 patients had reactive arthropathies. They show close relationships to each other and to other HLA-B27-associated spondyloarthropathies. The differentiation of this group of diseases from the juvenile rheumatoid arthritis is possible and relevant. PMID- 3106791 TI - c-myc gene expression and interleukin-2 receptor levels in cloned human CD2+,CD3+ and CD2+,CD3- lymphocytes. AB - The levels of c-myc mRNA and interleukin-2 receptors (IL-2 Rec) were studied in human peripheral blood lymphocytes (PBL); mature CD2+,CD3+ T cell clones and CD2+,CD3- natural killer (NK) cell clones, and CD2+,CD3+ and CD2-,CD3- T lymphoma cell lines. A transient induction of the expression of c-myc and IL-2 Rec was observed in PBL after activation with phytohemagglutinin (PHA). Expression of c myc and IL-2 Rec was also found in the CD2+,CD3+ and CD2+,CD3- clones. The CD2+,CD3+ showed higher levels of c-myc mRNA and IL-2 Rec than the CD2+,CD3- clones. In three T lymphoma cell lines constitutively high levels of c-myc mRNA but no IL-2 Rec were found. Only in JURKAT (CD2+,CD3+), c-myc mRNA levels could be further enhanced by PHA. These results suggest that in the presence of PHA, expression of c-myc and IL-2 Rec is induced via the CD3 receptor, and in the absence of PHA and/or the CD3 receptor alternative routes of induction are involved. PMID- 3106793 TI - Bilateral chylothorax secondary to subclavian vein catheterization: a case report. PMID- 3106792 TI - Serious infections in the elderly. PMID- 3106794 TI - [Study of the 210-degree region of the Bacillus subtilis chromosome using recombinant plasmids]. AB - The 210 degrees region of Bacillus subtilis DNA containing the rib operon and genes for the first (dapA) and last (lysA) steps of lysine biosynthesis was cloned. PstI fragments of B. subtilis m.m. 4.7 MD DNA containing the lys and the proximal part of rib operon were isolated from different B. subtilis strains (SB25 and SHgW) and shown to have the same restriction and genetic maps. The restriction mapping of EcoRI fragment of B. subtilis m.m. 6.3 MD DNA containing the rib operon has been carried out. PMID- 3106795 TI - [Transport of basic amino acids into Yersinia pestis cells]. AB - The transport of the basic amino-acids into the plague microbe cells has been shown to proceed by means of two transfer systems, the common transfer system and the system specific for lysine. Besides that, arginine can be transported into the plague microbe cells by the histidine transport system. The vaccine strain EV NIIEG was used as a model to study the amino-acid transport systems. PMID- 3106796 TI - Chromosomal instability in mutagen-sensitive mutants isolated from mouse lymphoma L5178Y cells. II. Abnormal induction of sister-chromatid exchanges and chromosomal aberrations by mutagens in an ionizing radiation-sensitive mutant (M10) and an alkylating agent-sensitive mutant (MS1). AB - To determine the mutual relationships between cell survival and induction of sister-chromatid exchanges (SCEs) as well as chromosomal aberrations (CAs), mutagen-induced SCEs and CAs were analyzed in an ionizing radiation-sensitive mutant (M10) and an alkylating agent-sensitive mutant (MS 1) isolated from mouse lymphoma L5178Y cells. The levels of CA induction in both mutants strictly corresponded to the sensitivity to lethal effects of mutagens, except that caffeine-induced CAs in M10 are considerably lower than those in L5178Y. The results clearly indicate that except for caffeine-induced CAs in M10, mutagen induced lethal lesions are responsible for CA induction. In contrast, SCE induction in mutants was complicated. In M10, hypersensitive to killing by gamma rays, methyl methanesulfonate (MMS), and 4-nitroquinoline 1-oxide (4NQO), but not sensitive to UV or caffeine, the frequency of SCEs induced by gamma-rays was barely higher than that in L5178Y, and the frequencies of MMS- and UV-induced SCEs were similar to those in L5178Y, but 4NQO- and caffeine-induced SCEs were markedly lower than those in L5178Y. MS 1, which is hypersensitive to MMS and caffeine, but not sensitive to UV or 4NQO, responded to caffeine with an enhanced frequency of SCEs and had a normal frequency of MMS-induced SCEs, but a reduced frequency of UV- and 4NQO-induced SCEs. Thus, susceptibility to SCE induction by mutagens is not necessarily correlated with sensitivity of mutants to cell killing and/or CA induction by mutagens. Furthermore, the spontaneous levels of SCEs are lower in M10 and higher in MS 1 than that in L5178Y (Tsuji et al., 1987). Based on these results, we speculate that M10 may be partially defective in the processes for the formation of SCEs caused by mutagens. On the other hand, MS 1 may modify SCE formation-related lesions induced by UV and 4NQO to some repair intermediates that do not cause SCE formation. In addition, MMS-induced lethal lesions in MS 1 may not be responsible for SCE induction whereas caffeine induced lethal lesions are closely correlated with SCE induction. Thus, the lesions or mechanisms involved in SCE production are in part different from those responsible for cell lethality or CA production. PMID- 3106797 TI - 4NQO- or MNNG-resistant variants established from a human cell line, RSb, with high sensitivity to both agents. AB - From a human cell line, RSb, with high sensitivity to the killing effects of 4 nitroquinoline 1-oxide (4NQO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 254-nm ultraviolet light, a 4NQO-resistant variant, Qr-10, and an MNNG-resistant one, Gr-10, were established using ethyl methanesulfonate as the mutagen. Cell proliferation studies and colony-formation assays revealed that Qr-10 and Gr-10 cells actively proliferated under conditions where RSb cell proliferation was greatly inhibited by 4NQO and MNNG, respectively. Total cellular DNA synthesis, as estimated by [Me-3H]thymidine uptake into acid-insoluble cell materials, was depressed in 4NQO-treated Qr-10 and MNNG-treated Gr-10 cells as it was in chemical-treated RSb cells, but recovered more markedly from such inhibition in the variants. 4NQO- and MNNG-induced DNA-repair replication synthesis was enhanced to a greater extent in Qr-10 and Gr-10 cells, respectively, than in RSb cells. The Qr-10 and Gr-10 cells showed the same respective susceptibility to the effects of MNNG and 4NQO, on cell growth and DNA synthesis and DNA-repair synthesis as did the parent cells. But, Qr-10 cells had more resistance to UV killing and higher levels of UV-induced DNA-repair synthesis than did RSb cells, while UV-susceptibility of Gr-10 cells was the same as that of the latter. PMID- 3106798 TI - On the localization of mitomycin C-induced aberrations in normal human and Fanconi's anaemia cells. AB - This paper summarizes the results of a series of experiments with primary cultures of normal human fibroblasts and lymphocytes designed to investigate chromatid aberration 'break-point' localization after a 1-h pulse of mitomycin C. For discontinuities and interchanges, 60-70% of the inferred 'break-points' were localized to defined paracentric heterochromatin and the centromeric regions (i.e. approximately 21% by length of the normal karyotype), irrespective of 'dose', aberration frequency, sample time or cycle sub-phase as determined by replication banding. Chromatid intrachanges are non-(or negatively) localized because of an inescapable scoring bias. SCE in fibroblasts show no such localization. Cells from a number of Fanconi's anaemia subjects were examined. In poorly growing cultures, localization was as high as in normal cells but in vigorous cultures localization was reduced to approximately 30%. It is suggested that the enhanced aberration sensitivity of this syndrome could arise because non localized aberrations, usually eliminated before division in normal cells, are allowed to reach mitosis in FA cells. PMID- 3106799 TI - Different effects of 1-beta-D-arabinofuranosylcytosine and aphidicolin in S-phase cells--chromosome aberrations, cell-cycle delay and cytotoxicity. AB - Some effects of a 2-h exposure to either aphidicolin (APC) or cytosine arabinoside (ara-C) on S-phase cells of the cell line JU56 have been measured. At a concentration of 1.5 X 10(-5) M of either drug, incorporation of tritiated thymidine into log-phase cultured was reduced by 97-99%. A 2-h exposure to either drug at the same concentration induced chromosome aberrations in cells in S when they subsequently reached mitosis. However, exposure to ara-C induced small numbers of aberrations per damaged cells, and most cells were undamaged. Exposure to APC induced gross chromosomal damage (pulverized chromosomes) in damaged cells. More cells were delayed, and for longer, after exposure to APC than after exposure to ara-C. The results of clonal assays were consistent with the assumption that chromosome aberrations are the proximal cause of reproductive cell death. In the case of ara-C, the results of this and a previous study are consistent with the assumption that cell death and chromosome aberrations are correlated with incorporation of ara-C into DNA in S-phase cells, but that these biological effects manifest themselves only with doses when inhibition of semi conservative DNA synthesis is greater than 97%. PMID- 3106800 TI - The roles of different excision-repair mechanisms in the resistance of Micrococcus luteus to UV and chemical mutagens. AB - M. luteus mutants showing increased sensitivity to both UV and 4-NQO were isolated after the treatment of parental ATCC4698 strain with MNNG. The mutants were also highly sensitive to mitomycin C, cis-platinum, 8-methoxypsoralen (8 MOP) plus near-UV and angelicin plus near-UV in various degrees. The endonuclease activity specific for pyrimidine dimers in UV-irradiated DNA was normally detected in extract of the mutants. With regard to host-cell reactivation ability the mutants fell into two groups. The hcr- mutants lacked the ability to reactivate UV-damaged N6 phage and were resistant to X-rays. The incision of DNA did not occur during incubation after the treatment with angelicin plus near-UV in the hcr- mutants, whereas it occurred in the parental strain. The facts indicate that the hcr- mutants are defective in the incision mechanism which has a wide substrate specificity, similar to the UVRABC nuclease of E. coli. On the other hand, the incision of DNA and the removal of UV-induced thymine dimers from DNA occurred in the hcr- mutants as well as in the parental strain, which is ascribed to the UV endonuclease activity. Compared with the hcr- mutants, hcr+ mutants were highly sensitive to X-rays, like recA- mutants of E. coli. PMID- 3106801 TI - Isolation and cross-sensitivity of X-ray-sensitive mutants of V79-4 hamster cells. AB - The V79-4 Chinese hamster line was mutagenized and surviving clones screened for X-ray sensitivity using a replica microwell technique. One slightly sensitive clone and 3 clearly sensitive clones were isolated from approximately 5000 screened, and designated irs 1 to irs 4. The 3 more sensitive clones showed different responses to the genotoxic agents mitomycin C (MMC), ethyl methanesulphonate (EMS) and ultraviolet light (UV). irs 1 showed considerable sensitivity to all the agents tested, in the order MMC much greater than EMS greater than UV. irs 2 and irs 3 had similar sensitivities to EMS and to UV (EMS greater than UV) but irs 3 was more sensitive than irs 2 to MMC. None of these mutants is identical in phenotype to previously published mutants. PMID- 3106802 TI - O6-methylguanine-DNA methyltransferase and alkylation of liver DNA in mice exposed to dimethylnitrosamine during dietary deficiency of essential amino acids. AB - Male NMRI mice were fed a diet containing a complete mixture of amino acids or a mixture deficient in methionine-cysteine or lysine (30% of the control level) for a period of 6 days. During the feeding period all mice received dimethylnitrosamine in the drinking water ad libitum. The exposure averaged 1 mg dimethylnitrosamine/kg body weight and day. The concentration of O6-methylguanine DNA methyltransferase was measured in liver extracts. It decreased significantly in the methionine-cysteine deficient mice. When DNA from the liver was analyzed for alkylated purine bases the mice received a single dose of 14C-labeled dimethylnitrosamine (0.5 or 1 mg/kg body weight) at 120 min before sacrifice. The concentration of O6-methylguanine increased significantly over the control level upon feeding the deficient diets and was restored to the concentration of the controls by refeeding lysine for 2 days following 6 days of lysine deficiency. The increased ratio of O6-methylguanine to N-7-methylguanine indicated that methylation of guanine in the N-7 position was not subject to variation by the intake of dimethylnitrosamine during the dietary deficiencies. The results demonstrate the requirement for a balanced composition of amino acids in the diet to maintain a sufficient concentration of O6-methylguanine-DNA methyltransferase in the cells and thus to permit efficient removal of the methyl group from the O 6 position of guanine in DNA after exposure to dimethylnitrosamine. PMID- 3106803 TI - Mutational activation of oncogenes in animal model systems of carcinogenesis. PMID- 3106804 TI - Influence of S9 mix in the induction of SOS system by quercetin. AB - The induction of recA, umuC and sfiA genes by quercetin was studied in the presence and in the absence of S9 mix. The inducing activity of quercetin is higher for sfiA than for recA and umuC genes in the absence of S9 mix. The putative genotoxic metabolites of quercetin produced by S9 mix display different inducing activities of the three SOS genes as compared to quercetin. The induction of sfiA gene is decreased by the presence of S9 mix, whereas an opposite effect was observed concerning umuC and recA. These data suggest that the error-prone repair pathway participates in mutagenesis by quercetin and its metabolites. Moreover, the type of DNA damage exerted by quercetin seems to be determined by its metabolic fate. The importance of testing for the induction of other SOS genes, together with sfiA, in the study of SOS functions as a genotoxic index is emphasized. PMID- 3106805 TI - Mutagenicity studies in Drosophila melanogaster with Lannate 20. AB - Lannate 20 a carbamate pesticide was evaluated for its mutagenicity in Drosophila melanogaster by the sex-linked recessive lethals and chromosome II-III translocation tests by continuous larval feeding. The 3 sublethal doses of 0.2, 0.4 and 0.6 microliter of Lannate per 100 ml of the food medium induced a significant (P less than 0.01) increase in the number of sex-linked recessive lethals over the controls. However, no translocations were observed either in the treated or the control series. PMID- 3106806 TI - A test using cultured cells with induced mixed-function oxygenase in the unscheduled DNA synthesis assay for detecting promutagens/procarcinogens. AB - The human FL cell line contains very low levels of constitutive AHH activity, but it could be greatly induced by NE, beta-NF and 3-MC, and induced slightly by PB. When two different types of inducer, for example, 3-MC and PB or 3-MC and NE were given in combination, an additive inductive effect was not observed. Both the constitutive and induced AHH in FL cells have characteristics of MFO, namely, NADPH-dependence and CO-sensitivity. The fact that the constitutive and induced AHH in FL cells could be inhibited by a known hydroxylase inhibitor 7,8-BF indicated that the AHH in FL cells belongs to the cytochrome P-448 dependent MFO type. After removal of inducer from the medium, the induced AHH activity remained at a high level for at least 24-36 h. By using AHH-induced FL cells in the UDS assay system for the detection of promutagens/procarcinogens, we found that AFB1 and 3-MC did not induce a UDS reaction in uninduced FL cells, while in beta-NF induced cells, 10(-6)-10(-4) M AFB1 and 10(-7)-10(-6) M 3-MC elicited a very significant UDS reaction, which was concordant with the results obtained in the UDS assay system using HeLa cells or FL cells supplemented with liver microsomes or using primary cultured hepatocytes as indicator cells. B(a)P elicited the UDS reaction at concentrations of 10(-6)-10(-3) M in beta-NF induced cells, whereas 10(-4)-10(-3) M was required in uninduced cells. The results above indicate that this new design is feasible, but further study is needed to assure its accuracy. PMID- 3106807 TI - Surface carbohydrates of procyclic forms of African trypanosomes studied using fluorescence activated cell sorter analysis and agglutination with lectins. AB - Living culture form procyclics of Trypanosoma brucei brucei, T.b. rhodesiense, T.b. gambiense, T. congolense and T. simiae were tested for binding of eight different lectins. The binding of fluorescein isothiocyanate (FITC)-conjugated lectins was measured using a fluorescence activated cell sorter (FACS) and by agglutination with unlabelled lectins. Five of the lectins failed to bind to any of the procyclic organisms in both tests. All parasites bound concanavalin A (Con A) and all T.b. brucei, T.b. rhodesiense and T. congolense procyclics bound Ricinus communis agglutinin 120 (RCA) and wheat germ agglutinin (WGA). Trypanosoma b. gambiense procyclics failed to bind RCA and thus could be easily discriminated from other subspecies of T. brucei. Similarly, T. simiae did not bind WGA, unlike T. congolense, the other species of the genus Nannomonas. All positive reactions were inhibited by 0.2 M concentrations of the relevant sugars. The results indicate that all species and subspecies of the procyclic culture forms tested have surface-exposed structures resembling alpha-D-mannose moieties and that T.b. brucei, T.b. rhodesiense and T. congolense have surface-exposed molecules resembling D-galactose and N-acetyl D-glucosamine (or sialic acid) moieties. Molecules resembling D-galactose and N-acetyl D-glucosamine residues are absent or inaccessible in T.b. gambiense and T. simiae respectively. A group of T. congolense clones of parasite stocks isolated at Kilifi on the Kenyan coast showed quantitatively different binding of RCA when compared to the other T. congolense clones tested indicating that these organisms differ in surface carbohydrate structure. PMID- 3106809 TI - A hard look at cost containment. PMID- 3106808 TI - Uniform detection of immunoglobulin-gene rearrangement in benign lymphoepithelial lesions. AB - The term "benign lymphoepithelial lesion" is used to describe the salivary-gland lymphocytic infiltration and epithelial changes typically found in association with Sjogren's syndrome. We used Southern blot hybridization techniques to examine the immunoglobulin genes in salivary-gland tissue derived from eight patients with benign lymphoepithelial lesions. Three of these patients had intrasalivary non-Hodgkin's lymphoma complicating the lesions, whereas the lesions in the remaining five were all histologically benign. Ten samples from the eight patients all revealed rearrangement of both the heavy-chain and light chain immunoglobulin genes. In one of the patients in whom non-Hodgkin's lymphoma involved both the salivary-gland lesion and an ipsilateral lymph node, the rearrangements of the heavy-chain and light-chain immunoglobulin genes detected at the two sites were identical. One other patient had two distinct benign lymphoepithelial lesions removed two years apart. The rearrangements of the heavy chain as well as the kappa light-chain genes detected in these two lesions were entirely different. These data suggest that B-cell clonal expansion has an integral role in the pathophysiology of the benign lymphoepithelial lesion and may explain the increased incidence of lymphoma noted in association with this disorder. PMID- 3106810 TI - Increased concentrations of cholestanol and apolipoprotein B in the cerebrospinal fluid of patients with cerebrotendinous xanthomatosis. Effect of chenodeoxycholic acid. AB - We investigated the effect of chenodeoxycholic acid on cerebrospinal fluid sterol and protein composition in six patients with cerebrotendinous xanthomatosis, a progressive neurologic disease, and in 11 control subjects. In the cerebrospinal fluid from the controls, the mean (+/- SD) levels of cholesterol and cholestanol were 400 +/- 300 and 4 +/- 7 micrograms per deciliter, respectively. The levels were almost 1.5 and 20 times higher in cerebrospinal fluid from untreated patients with cerebrotendinous xanthomatosis. Cholestanol levels were also markedly elevated in the plasma of untreated patients, but their plasma cholesterol levels (215 +/- 61 mg per deciliter) were not different from control values. Treatment with chenodeoxycholic acid reduced cerebrospinal fluid cholesterol by 34 percent and cholestanol threefold. Plasma cholestanol levels also decreased sharply. Normal cerebrospinal fluid contained small quantities of albumin, apolipoproteins, and lecithin:cholesterol acyltransferase. In cerebrospinal fluid from untreated patients with cerebrotendinous xanthomatosis, immunoreactive apolipoprotein B or apolipoprotein B fragment was increased about 100-fold and albumin about 3.5-fold; apolipoprotein AI, apolipoprotein D, and lecithin:cholesterol acyltransferase were 1.5 to 3 times more concentrated. Apolipoprotein AIV and apolipoprotein E concentrations were comparable to those in controls, and apolipoprotein AII was considerably decreased. During treatment, the concentrations of albumin and apolipoproteins AI and B declined. These results suggest that increased cerebrospinal fluid sterols are derived from plasma lipoproteins by means of a defective blood-brain barrier in patients with cerebrotendinous xanthomatosis. Therapy with chenodeoxycholic acid reestablished selective permeability of the blood-brain barrier and normalized the concentrations of sterol and apolipoprotein in the cerebrospinal fluid. PMID- 3106812 TI - Genetic and biological markers in drug abuse and alcoholism. PMID- 3106811 TI - Aflatoxin B1 production in orange (Citrus reticulata) juice by isolates of Aspergillus flavus Link. AB - Out of 7 isolates of Aspergillus flavus obtained from rotting orange (Citrus reticulata) fruits, 3 isolates were found to be toxigenic, producing variable amounts of aflatoxin B1 on a semisynthetic liquid medium. The most toxigenic isolates were further evaluated in plain juice and juice supplemented either with 0.05% yeast extract or 0.5% sucrose or both, at three different incubation periods. The maximum yield of aflatoxin B1 (162.5 micrograms/25 ml) was obtained from the juice supplemented with both sucrose and yeast extract within an incubation period of 10 days, whereas a sharp decline in aflatoxin B1 (30 micrograms/25 ml) was observed when incubation was extended beyond 10 days. The addition of yeast extract has a promoting effect on the yield of aflatoxin in comparison to the sucrose. PMID- 3106813 TI - Genetic and biological markers in drug abuse and alcoholism: a summary. PMID- 3106814 TI - Recommendations for future research on genetic and biological markers in drug abuse and alcoholism. PMID- 3106815 TI - Individual differences in opiate-induced alterations at the cytogenetic, DNA repair, and immunologic levels: opportunity for genetic assessment. PMID- 3106816 TI - Pharmacogenetic approaches to the prediction of drug response. PMID- 3106817 TI - Studies on an animal model of alcoholism. AB - Past and ongoing studies indicate that the selectively bred P line of rats satisfies virtually all the suggested criteria for an animal model of alcoholism. They attain pharmacologically active levels of BAC and develop tolerance and physical dependence with voluntary oral ethanol ingestion, while in the free feeding state. Ethanol is positively reinforcing to the P rats and consumption appears to be directed by the post-ingestive, pharmacological effects of ethanol, as revealed by the intragastric self-administration studies. Some interesting differences between the P and the NP lines have been uncovered. They differ in the content of serotonin in several brain regions and they respond differently to ethanol. The P rats develop acute tolerance to sedative-hypnotic doses of ethanol more rapidly than do the NP rats, and they exhibit stimulation with low doses of ethanol. These differences suggest hypotheses on mechanisms underlying alcohol seeking behavior which can now be tested experimentally. It should be emphasized, however, that the described findings are the product of but a single genetic experiment. Clearly, replication is needed, and we are currently doing this, using a better defined, heterogeneous stock of rats. This one experiment, however, has demonstrated the feasibility of developing animal models of alcoholism and offers hope that the genetic and biological basis of alcohol seeking behavior can be explored in the laboratory. The screening and testing of pharmacological agents able to deter alcohol-seeking behavior is an obvious practical application of this model. PMID- 3106818 TI - Genetics as a tool for identifying biological markers of drug abuse. PMID- 3106819 TI - Genetic markers of drug abuse in mouse models. PMID- 3106820 TI - Inheritance of risk to develop alcoholism. PMID- 3106821 TI - Genetic and biological markers in alcoholism and drug abuse. PMID- 3106822 TI - Evolution east of Eden. PMID- 3106823 TI - Behaviour modification by in vitro mutagenesis of a variable region within the period gene of Drosophila. AB - The period gene of Drosophila melanogaster, implicated in the control of both the circadian and male courtship song rhythms, is found to be polymorphic. Alleles differ in the length of a region of the gene encoding a series of threonine glycine repeat units. The phenotypes of transformed fruit flies, in which the only functional period gene lacks the entire perfect threonine-glycine repeat region, show that the effects of the period gene on the circadian and male courtship song rhythms can be dissociated. PMID- 3106824 TI - Interleukin-2 and GTP binding in lymphocytes. PMID- 3106825 TI - Expression and functional characterization of artificial mutants of interleukin-2 receptor. AB - The physiological proliferation of T lymphocytes (T cells) requires interaction between the humoral growth factor, interleukin 2 (IL-2) and its cell-surface receptor. Studies of IL-2 binding to the IL-2 receptor (IL-2R) on T cells have revealed that there are two distinct species of IL-2R, one with high and one with low affinity. Isolation and characterization of cDNA for the human IL-2R made it possible to deduce the complete primary sequence (251 residues) of the receptor protein. However, expression of IL-2R alone is not sufficient for either growth signal transduction or high-affinity site formation: another lymphocyte-specific molecule called converter seems to be required for the biological activity of IL 2R. We found that the converter did not form a stable complex with IL-2R unless the receptor bound the ligand (the 'affinity conversion' model). To discover which are the functionally important parts of the human IL-2R we have constructed artificial mutant cDNAs encoding the receptor. The mutant receptors produced from them had deletions or substitutions in the cytoplasmic region (13 residues), the transmembrane region (19 residues) or the carboxy-terminal portion of the extracellular region (219 residues). All were active in growth signal transduction, efficient internalization and high-affinity site formation in two mouse T-cell lines, suggesting that the extracellular region of IL-2R and the converter may be responsible for growth signal transduction. PMID- 3106826 TI - Release of mature starfish oocytes from interphase arrest by microinjection of human centrosomes. AB - Mature oocytes (unfertilized eggs) are arrested at definite cell-cycle stages which vary from species to species. In frogs and mammals, the oocytes are arrested at the second metaphase of meiosis whereas in echinoderms they are blocked later, at the pronucleus stage. What causes the maturing oocytes to stop at some point in the cell cycle is not entirely clear. In frogs, the metaphase arrest seems to be maintained by a cytostatic factor. In echinoderms, which stop at interphase, no such a factor has so far been found. The fertilization process, beyond the introduction of paternal chromosomes, releases the oocyte from cell cycle arrest and provides a functional centrosome to replace the endogenous centrosome which is apparently lost during oogenesis in most species. Several lines of evidence suggest that release from cell-cycle arrest is mediated by a Ca2+ burst which is associated with fertilization, and it is known that the functional centrosome provided by the sperm is necessary for mitotic spindle formation and cleavages. We report here that microinjection of purified human centrosomes into mature starfish oocytes is sufficient to release them from arrest at interphase and to support many cleavages leading to the occasional formation of normal embryos. In this species centrosome induced re-entry into the cell cycle does not require a transient calcium burst nor does it require intact microtubules. PMID- 3106827 TI - Blood products lab. PMID- 3106828 TI - Who is the 'real' Homo habilis? PMID- 3106829 TI - G proteins and diabetes. PMID- 3106830 TI - Circular T-cell receptor gene recombination products. PMID- 3106831 TI - New partial skeleton of Homo habilis from Olduvai Gorge, Tanzania. AB - A new partial skeleton of an adult hominid from lower Bed I (about 1.8 Myr ago), Olduvai Gorge, is described. This specimen's craniodental anatomy indicates attribution to Homo habilis, but its postcranial anatomy, including small body size and relatively long arms, is strikingly similar to that of some early Australopithecus individuals. PMID- 3106832 TI - Abolition of the expression of inhibitory guanine nucleotide regulatory protein Gi activity in diabetes. AB - Many cell-surface receptors for hormones appear to exert their effects on target cells by interacting with specific guanine nucleotide binding regulatory proteins (G-proteins) which couple receptors to their second-messenger signal generation systems. A common intracellular second messenger, which is used by many hormones, is cyclic AMP. This is produced by adenylate cyclase, whose activity is controlled by two G-proteins, Gs which mediates stimulatory effects and Gi inhibitory effects on adenylate cyclase activity. In liver, the hormone glucagon increases intracellular cAMP concentrations by activating adenylate cyclase by a Gs-mediated process. This effect of glucagon is antagonised by the hormone insulin, although the molecular mechanism by which insulin elicits its actions is obscure. However, insulin receptors exhibit a tyrosyl kinase activity and appear to interact with G-proteins, perhaps by causing phosphorylation of them. In type I diabetes, circulating insulin levels are abnormally low, giving rise to gross perturbations of metabolism as well as to a variety of complications such as ionic disturbances, neuropathies of the nervous system, respiratory and cardiovascular aberrations and predisposition to infection. We show here that experimentally-induced type I diabetes leads to the loss of expression of Gi in rat liver. As it has been suggested that Gi may couple receptors to K+-channels as well as mediating the inhibition of adenylate cyclase, aberrations in the control of expression of this key regulatory protein in type I diabetes may be expected to lead to pleiotropic effects. PMID- 3106833 TI - Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta. AB - The vascular endothelium, in response to pulsatile flow and vasoactive agents including acetylcholine, secretes the endothelium-derived relaxing factor (EDRF), a substance which regulates vascular tone. Recent interest in EDRF has focused on its possible dysfunction in atherosclerosis. In animal models of the disease, endothelium-dependent relaxation is markedly reduced. The continuous exposure of the endothelium in hyperlipidaemia to high concentrations of low-density lipoprotein (LDL), a known atherogenic risk factor, may explain this dysfunction. Here, we demonstrate that pathophysiological concentrations of LDL directly inhibit endothelium-dependent relaxation. Chemically modified LDL, in contrast, is inactive, implying that the inhibition is through a receptor-dependent mechanism. PMID- 3106834 TI - Interactions between DNA and coat protein in the structure and assembly of filamentous bacteriophage fd. AB - Bacteriophage fd is a class I filamentous virus (others are M13 and f1) that comprises a circular, single-stranded DNA molecule enclosed in a cylindrical protein sheath to form a flexible particle approximately 890 nm long and 7 nm in diameter. The viral DNA contains 6,408 nucleotides incorporating 10 genes, and the protein sheath is composed of about 2,700 major coat protein subunits in a shingled helical array, the symmetry of which is defined by a fivefold rotational axis combined with a twofold screw axis of pitch 3.2 nm. The DNA extends throughout the length of the particle but is not base-paired and has a symmetry different from that of the protein helix. How the DNA is packed remains unclear but the number (2.4) of nucleotides packaged per major coat protein subunit is certainly not integral, in contrast with, say, the packaging of RNA in tobacco mosaic virus. The coat protein subunit is 50 amino-acid residues in length and, in the virus particle, adopts a largely alpha-helical conformation, with the long axis of the helix aligned close to the long axis of the filament. This protein is arranged with its negatively charged N-terminal region on the outside of the filament and its positively charged C-terminal region on the inside abutting the DNA. We report here that positive charge on one of the four lysine side chains in the latter region has a direct effect on DNA packaging, because when this charge is absent, elongated particles are produced with lengths that can be correlated with the residual positive charge in the C-terminal region of the coat protein subunit. PMID- 3106835 TI - [Hormonal aspects of normal spermatogenesis and its disorders]. PMID- 3106836 TI - [Cost-effectiveness of follow-up studies after curative surgery of colon or rectum carcinoma]. PMID- 3106837 TI - [Mortality of undiagnosed type I diabetes mellitus in 0-19-year-olds in the Netherlands]. PMID- 3106838 TI - [An alternative to the heat treatment of factor VIII products: the quarantine method]. PMID- 3106839 TI - [Brain death, a continuing discussion?]. PMID- 3106840 TI - [Cost-benefit analysis of the diagnosis of patients with deep venous thrombosis]. PMID- 3106841 TI - [Diagnosis of the hyperventilation syndrome]. PMID- 3106842 TI - [Rehabilitation of chronic schizophrenic patients in long-term communities]. PMID- 3106845 TI - Mannitol-induced acute renal failure. AB - Mannitol is an osmotic diuretic widely used in the diagnosis and prevention of acute oliguric renal failure, acute cerebral edema and acute glaucoma. Mannitol, though ordinarily a benign substance, may accumulate in renal failure with potentially deleterious consequences. Mannitol intoxication is ordinarily characterized by confusion, lethargy, stupor, and if severe enough, coma. The use of mannitol in renal failure has rarely been associated with a worsening of the preexistent renal dysfunction. We report a case of acute oliguric renal failure solely attributable to mannitol administered in the course of therapy for acute glaucoma. PMID- 3106846 TI - Hyperthyroidism and high serum levels of TSH associated with pituitary tumour. AB - We report a 28-year-old male with persistent clinical and laboratory findings of hyperthyroidism associated with marked elevated serum levels of TSH and no response to TRH despite hemithyroidectomy and subsequent antithyroid drug therapy two years previous to admission to our hospital. Subsequent skull X-rays, CT scans and angiographic findings demonstrated the presence of a pituitary tumour. After operation and radiation therapy T3, T4 and TSH levels returned to normal values. Seven years later the patient is still euthyroid. We conclude that hyperthyroidism in our patient was due to excessive secretion of TSH by the pituitary tumour. PMID- 3106848 TI - Efficacy and safety of tissue plasminogen activator. AB - Simple aspiration to remove acute intracerebral hematomas has been thwarted by the solidity of the clot. Urokinase, a first generation fibrinolytic agent, has been used to liquefy such clots with some success. Therefore, tissue plasminogen activator (t-PA), a second generation fibrinolytic drug that may be safer and more effective, was studied to evaluate its ability to lyse clot in vitro and its reactivity in the brain and subarachnoid space. t-PA seems to cause partial clot lysis in small dosages (3750 units/70-cc clot) and in a short time (15 minutes). It seems to perfuse through the clot when injected in one place. It does not cause inflammation or bleeding when injected into the rat brain, but indeed seems to promote resorption of blood when the two are injected together. It does not cause aseptic meningitis when injected into the cisterna magna of rabbits. t-PA may prove to be an important adjuvant to the stereotactic aspiration of intracerebral hematomas. It may be particularly helpful in lysing these clots to make possible more gentle aspiration, removing the risk to surrounding brain of strong vacuum. PMID- 3106847 TI - Bimodal effects of neuropeptide Y on hypothalamic release of gonadotropin releasing hormone in conscious rabbits. AB - Neuropeptide Y (NPY) is present in large quantities in the hypophysiotropic areas of the brain and has a similar distribution pattern as gonadotropin-releasing hormone (GnRH). The aim of this study was to measure GnRH release during perfusion of NPY through the mediobasal hypothalamus of intact and ovariectomized (OVEX) does. Does were fitted with push-pull (PP) cannulae directed into the median eminence and were subjected to subsequent PP perfusion at a flow rate of 20 microliters/min for a total of 6 or 8 h. Six intact does and seven OVEX does received intrahypothalamic perfusion of NPY (14 micrograms/ml) for either 2 or 3.5 h during the 6 or 8 h, respectively, of PP perfusion. The PP samples and femoral vein blood samples were collected at 10-min intervals on ice. Perfusate GnRH and plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) levels were measured by specific radioimmunoassays. The pulsatile parameters of all hormones were analyzed by the 'PULSAR' program. Perfusion of NPY significantly decreased mean levels, pulse amplitudes, and pulse frequencies of GnRH in OVEX does. Also, mean levels of LH were decreased, whereas levels of FSH and PRL were unaffected by NPY. In contrast to these inhibitory effects on GnRH in OVEX does, the same NPY perfusion stimulated mean levels and pulse amplitudes of GnRH in intact does. Plasma levels of neither gonadotropin nor PRL were affected significantly by the NPY treatment in intact rabbits. These results indicate that NPY may have central effects on neuronal release of GnRH, and that ovarian factors are critical in the directional mode of these NPY actions. PMID- 3106849 TI - Ossified prolactinoma: case report. AB - The authors report a case of ossified prolactinoma that was identified as a calcified nodule on the roentgenograms. Histologically, the ossified tissues were diffuse, and the osteoid was mineralized in various degrees, subsequently forming bones. Adenoma cells were sparse among the ossified tissues. This is probably the first report of ossified pituitary adenoma associated with osteoid metaplasia. The pathogenesis of osteoid metaplasia in pituitary adenomas is possibly due to proliferative connective tissue resulting from degeneration of the pituitary adenoma; this connective tissue may possess osteogenic potency. PMID- 3106850 TI - Lack of withdrawal signs of dependence following cessation of treatment or Ro 15,1788 administration to rats chronically treated with buspirone. AB - Failure to gain weight during withdrawal from chronic regimens of dependence producing drugs is observed in laboratory rats. Withdrawal from the benzodiazepine anxiolytic agent diazepam, whether induced by cessation of treatment or precipitated by administration of the specific benzodiazepine antagonist Ro-15,1788, is accompanied by weight loss. However, the same withdrawal treatments following a chronic regimen of equal doses of the nonbenzodiazepine antianxiety drug buspirone are not associated with weight loss. Buspirone-treated rats gain weight during withdrawal, suggesting that this novel anxiolytic should lack dependence liability in man. PMID- 3106851 TI - Locomotor activity in relation to dopamine and noradrenaline in the nucleus accumbens, septal and frontal areas: a 6-hydroxydopamine study. AB - Locomotor activity was automatically recorded in a circular corridor in rats treated with 6-hydroxydopamine in the ventral tegmental area (VTA), septum and frontal cortex. Control and experimental groups showed similar hyperlocomotor responses in the novel apparatus lasting 3 h. Circadian changes are described. VTA lesions resulted in increased dark activity and a large response to apomorphine compared to other lesion and control groups. Septal lesions did not affect locomotion. The frontal group showed a small increase of locomotion after apomorphine treatment that might reflect increased receptor sensitivity in cortical or subcortical areas. Together with correlations between motor activity and cortical levels of dopamine and noradrenaline these results are interpreted to support a role for dopamine, noradrenaline and the frontal cortex in modulating locomotion which is primarily mediated by VTA-accumbens-dopamine activity. PMID- 3106852 TI - Visuospatial and motor attention in the monkey. AB - Visuospatial attention involves the selection of stimuli from the environment for further neural processing. The attention-related enhancement of visual responses in posterior parietal cortex is a possible neural substrate for visuospatial attention. By analogy with the selection process in the spatial domain, motor attention is postulated to involve a selection among simultaneous upper motor signals. Selection of motor programs within the oculomotor system is used as an example of this attentional process. Since attentive fixation modulates the effect on the oculomotor system of electrical stimulation of the frontal eye fields, a given upper motor neuronal signal need not necessarily invoke a movement. That the brain has multiple simultaneous motor signals is apparent from the profusion of sensory-driven upper motor neurons. The frontal cortex is probably important in selecting which upper motor signals actually evoke movements, by elaborating motor programs for purposive behavior, but not for all movements. PMID- 3106853 TI - Diagnosis of argininosuccinic aciduria after valproic acid-induced hyperammonemia. PMID- 3106854 TI - [Recklinghausen disease and hypertrophic cardiomyopathy. Description of a case with regional hypertrophy]. PMID- 3106855 TI - [Nutritional support in the surgery of hip fractures in the elderly. Experience and results]. PMID- 3106856 TI - Cryopreservation of mouse, monkey and human islets of Langerhans for transplantation purposes. AB - Transplantation of islets of Langerhans is a possible future therapy for insulin dependent diabetes mellitus. In contrast to total pancreas, isolated islets of Langerhans can be treated prior to transplantation to reduce their immunogenicity. Thus the success rate in allotransplantation of islets can be increased. The isolation of large amounts of islets from human pancreas is still a problem and islets from different donors have to be collected and stored by cryopreservation. In this paper we describe the methods used in our laboratory to isolate islets of Langerhans from rodent, monkey and human pancreas. The results are presented of successful cryopreservation of these islets. Firstly, by a more conventional freezing method using dimethylsulfoxide as cryoprotectant. Secondly, by vitrification using a mixture of cryoprotectants. The latter method has not been used previously for cryopreservation of islets. The integrity of the islets before and after freezing was tested in vitro and, for mice, in vivo. PMID- 3106857 TI - Pancreas transplantation in diabetes mellitus: solutions and enigmas. PMID- 3106858 TI - Mannitol-induced hyperosmolality and cerebrospinal fluid vasopressin in anesthetized cats. AB - Arginine-vasopressin (AVP) has been found to influence brain water. Since AVP is released by hyperosmolality into plasma we determined the role of AVP in controlling cerebrospinal fluid (CSF) pressure. Adult cats were anesthetized with pentobarbital and samples of plasma and cisternal CSF were collected 1 or 2 h before i.v. infusion of 2 g/kg of mannitol and for 2 h afterwards. We found a significant increase in plasma osmolality from 320.0 +/- 1.6 to 331.6 +/- -3.4 mOsm/l (mean +/- S.E.M.), while CSF osmolality was unchanged. Prior to mannitol infusion, AVP was elevated to 105 +/- 19 pg/ml in plasma and to 136 +/- 19 pg/ml (mean +/- S.E.M.) in CSF. After infusion of mannitol AVP levels were unchanged in either plasma or CSF. The reduction of CSF pressure by mannitol is independent of AVP in the anesthetized cat. PMID- 3106859 TI - 4-phenylpyridine and three other analogues of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine lack dopaminergic nigrostriatal neurotoxicity in mice and marmosets. AB - C57 black mice were injected repeatedly with maximal tolerated doses of 2 chemical analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); 4 phenylpyridine and 4-phenyl-1,2,3,6-tetrahydropyridine. Although both compounds were clearly acutely toxic to mice, neither caused any reduction in striatal dopamine content after chronic exposure. Two MPTP analogues which may be formed endogenously during the metabolism of brain monoamines, 2-methyl-1,2,3,4 tetrahydroisoquinoline and 2-methyl-1,2,3,4-tetrahydro-beta-carboline, were injected repeatedly into common marmosets. Again, although both compounds appeared highly toxic, neither caused any reduction in striatal dopamine content. It appears unlikely that any of these 4 MPTP analogues causes idiopathic Parkinson's disease. PMID- 3106861 TI - Preoperative nutritional support. PMID- 3106863 TI - Nutrition in the critically ill. PMID- 3106862 TI - Hyperalimentation of patients with obstructive jaundice. PMID- 3106860 TI - Turnover of central biogenic amines in one-kidney, one-clip renal hypertensive rats. AB - Turnover rates, as estimated from the accumulation of the intermediates, 3,4 dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) following decarboxylase inhibition, were used to investigate the relationship between central catecholaminergic and serotonergic neurons and the development of hypertension in the one-kidney, one-clip renal hypertensive rats. Results indicated that at one week following clipping, 5-HTP accumulation was decreased in the posterior hypothalamus. At 5 weeks no changes were observed. At 20 weeks higher accumulations of both DOPA and 5-HTP were observed in the medulla oblongata while in the anterior hypothalamus DOPA accumulation was increased. PMID- 3106864 TI - An analysis of the effect of percent of RN staff on nursing costs by DRG. PMID- 3106865 TI - Third-party billing. PMID- 3106866 TI - General downturn in Medicaid dentistry. PMID- 3106867 TI - Metal decomposition rates of 111In-DTPA and EDTA conjugates of monoclonal antibodies in vivo. AB - We have studied the metal chelate decomposition rates in vivo in both 111In labelled benzyl EDTA and DTPA (bicyclic anhydride) conjugates of monoclonal anti IAk IgG2a with identical Ka = 1 X 10(11)M-1 in both Ag+ve and Ag-ve mice. Twenty mu Ci was given i.v. and whole body counting done immediately and daily for 10 days, with six to eight mice in each group. Half the mice in each group received i.p. injections of 5.0 mg CaNa2 EDTA chase (Versenate) to facilitate urinary excretion of free 111In. 50% of control 111In-citrate remained at nine days but only 8% with chase. No significant loss of 111In with chase occurred with C1 substituted EDTA conjugates. A 19% increase in excretion was demonstrated with the chase in mice given DTPA conjugates (1.9% per day). While this will not interfere with radioimmunoimaging up to 24 h after injection, waiting periods of a week or longer will produce significant background of free 111In in the reticuloendothelial system, RES. 111In-EDTA stability was important in accurate metabolic rate measurements of anti-IAk; T1/2 = 7.0 days in Ag-ve mice, T1/2 = 9.3 days in Ag-ve mice. It will be important to measure the in vivo rates for each new metal complex, especially those intended for therapy such as Y-90. PMID- 3106868 TI - Cost-benefit analysis in radiation protection. PMID- 3106869 TI - Comparative utility of repeat Papanicolaou smears, cervicography, and colposcopy in the evaluation of atypical Papanicolaou smears. AB - In an attempt to establish the significance and management of the atypical Papanicolaou smear, 97 patients with atypical Papanicolaou smears were each evaluated with a repeat Papanicolaou smear, cervicography, and colposcopy. In the detection of significant lesions, cervicography was more sensitive than a repeat smear, but less so than colposcopy. Forty-two percent of the colposcopically detected lesions would have gone undetected by repeat Papanicolaou smears, compared with 11% by cervicography. However, Papanicolaou smears were more specific than cervicography (55 versus 29%). The cost per case detected using cervicography for triage was equal to that using follow-up Papanicolaou smears, but was a third higher than referring all patients directly to colposcopy. Merely using repeat smears in patients with atypical Papanicolaou smears may result in nondetection of many significant lesions, especially in populations where follow up is poor. PMID- 3106871 TI - Gonadotropin binding sites in human ovarian follicles and corpora lutea during the menstrual cycle. AB - Gonadotropin binding sites were localized by autoradiography after incubation of human ovarian sections with 125I-labeled gonadotropins. The binding sites for 125I-labeled human follicle-stimulating hormone (125I-hFSH) were identified in the granulosa cells and in the newly formed corpora lutea. The 125I-labeled human luteinizing hormone (125I-hLH) binding to the thecal cells increased during follicular maturation, and a dramatic increase was preferentially observed in the granulosa cells of the large preovulatory follicle. In the corpora lutea, the binding of 125I-hLH increased from the early luteal phase and decreased toward the late luteal phase. The changes in 3 beta-hydroxysteroid dehydrogenase activity in the corpora lutea corresponded to the 125I-hLH binding. Thus, the changes in gonadotropin binding sites in the follicles and corpora lutea during the menstrual cycle may help in some important way to regulate human ovarian function. PMID- 3106870 TI - The diagnosis of gonorrhea in a low-prevalence female population: enzyme immunoassay versus culture. AB - In a low-prevalence population for sexually transmitted disease, accurate methods of identifying Neisseria gonorrhoeae infections are of paramount importance. Tests with low sensitivity are of concern to each practitioner. Of no less concern, however, are the possible social and emotional consequences of a false positive test in a family-based, rural, or military community. Several centers serving high-prevalence populations have shown that the Gonozyme Enzyme Immunoassay may provide many advantages in the rapid detection of gonococcal infection in these groups. Few studies, however, have evaluated its efficacy in low-prevalence populations. We compared the Gonozyme with Martin-Lewis culture medium in 1490 women considered at risk for infection with N gonorrhoeae at Keesler USAF Medical Center, Mississippi. Fifty-three women had culture-proved infections (3.6% disease prevalence). The sensitivity and specificity of the Gonozyme in this population were 92.4 and 97.2%, respectively. However, the predictive value of a positive test was only 55.1%, mandating culture confirmation. It appears that in a low-prevalence female population, standard culture techniques provide a more efficient and reliable means of detecting N gonorrhoeae than does the Gonozyme Enzyme Immunoassay. PMID- 3106873 TI - Patient satisfaction--an attribute or indicator of the quality of care? AB - Systematic measurement of patient satisfaction is seldom included in routine quality assurance (QA) programs. Practical reasons have been given to explain this omission: the mental and physical state of patients, their lack of the necessary scientific and technical knowledge, the rapid pace of events of care, and methodological problems related to measuring patient satisfaction. However, a strong case can be made to include patient satisfaction in QA, including ethical considerations, philosophical changes occurring in the health care field, and a clear definition of the impact of patient satisfaction on quality care. This article concludes that patient satisfaction is part and parcel of quality health care; that patients are capable of assessing the quality of care; and that patient satisfaction can be measured. PMID- 3106872 TI - The effect of enzymatic contact lens cleaning on adherence of Pseudomonas aeruginosa to soft contact lenses. AB - Previous studies have demonstrated that Pseudomonas aeruginosa adheres more readily to soft contact lenses with a mucin coating than to unworn contact lenses. The mucin coatings that develop on soft contact lenses may, therefore, play a significant role in the pathogenesis of contact lens-associated Pseudomonas corneal ulceration. We tested the ability of a variety of enzymatic contact lens cleaners and other enzyme solutions to decrease the adherence of Pseudomonas to mucin-coated soft contact lenses. Of the commercially available solutions that were tested, cleaning with Optizyme and Extenzyme significantly reduced the adherence of Pseudomonas to the lenses, whereas cleaning with the Softmate Weekly Cleaning System had no effect. Optizyme and Extenzyme were as effective as a 10% solution of acetylcysteine and more effective than a 0.25% trypsin solution. Neuraminidase at pH 5 was the most effective solution at reducing the adherence of Pseudomonas to the lenses, supporting the finding that sialic acid is a specific receptor for Pseudomonas aeruginosa. Soft contact lenses should be cleaned frequently with an effective enzymatic cleaner to reduce the likelihood of Pseudomonas adhering to the lens and thereby reduce the incidence of Pseudomonas corneal ulceration in soft contact lens wearers. PMID- 3106874 TI - An audit of the effect of two cord-care regimens on bacterial colonization in newborn infants. AB - Proper care of the umbilical cord of newborn infants may prevent later infections. When St Joseph's Hospital in Hamilton, Ontario, started using alcohol instead of triple dye for umbilical cord care, there was a dramatic increase in the incidence of bacterial colonization in newborns in the nursery and, later, in the number of cases of staphylococcus-related skin infections in infants born at the hospital. Follow-up on 1,545 infants revealed that triple dye was significantly more effective than alcohol in reducing the growth of gram-positive organisms, especially Staphylococcus aureus and group B streptococcus, and several gram-negative organisms. Because hospital medical staff had carefully collected data on bacterial colonization, they were quickly aware of the problem and could justify resuming the use of triple dye. PMID- 3106875 TI - The Joint Commission's model for monitoring and evaluation of quality care. PMID- 3106876 TI - Toward meaningful blood usage review: comprehensive monitoring of physician practice. AB - During a one-year period, all blood transfusions at an acute care Veterans Administration hospital were concurrently reviewed. Inappropriate transfusion episodes represented less than 2% of the total according to clinical criteria established for purposes of screening cases. The percentage of episodes reviewed that did not meet the screening criteria decreased progressively (3.6% to 0.3%) during the study period. Episodes in which red blood cells (RBC) or fresh frozen plasma (FFP) alone and RBC and FFP together were transfused comprised almost all of the cases that were unjustified by peer review. The findings indicated that, although comprehensive review may document the overall appropriateness of clinical transfusion practice, more detailed profiling of clinical circumstances of each episode is necessary to provide convincing arguments for major revisions in hemotherapy practice. PMID- 3106877 TI - Quality of care for life-supported children who require prolonged mechanical ventilation at home. AB - Home care is now possible for ventilator-dependent children. It is crucial, however, to ensure that the children's conditions are medically stable and that their home care is carefully planned before they are discharged. The Ventilator Dependent Discharge Program at Children's Memorial Hospital in Chicago uses a comprehensive, multidisciplinary approach to discharge planning. The program includes training for parent caregivers, organization of community resources, and arrangement for funding. PMID- 3106878 TI - Taking care of the doctors: the hospital's duty to evaluate, monitor, and discipline its medical staff. AB - The heart of a hospital's credentialing responsibilities lies in its duties to evaluate, to monitor, and to discipline its medical staff. Some key elements of an effective credentialing system are the skills of the medical staff coordinator, the use of physician proctors to evaluate new applicants, careful investigation of applicants for initial appointment and for reappointment, and education for department chairmen. Inevitable problems include physicians who do not work harmoniously with others and allegations of incompetence and impairment. PMID- 3106879 TI - Clinical trials and technology assessment. AB - This article focuses on clinical trials in technology assessment. The relation between technology assessment... and quality assessment... is very close in this area, because the health benefits and safety of new interventions are tested in direct patient care. PMID- 3106880 TI - [Osteotomy using a CO2-laser]. PMID- 3106881 TI - [Possibility of restoring function after complete transection of the spinal cord and ways of achieving this goal (review of the problem. Part 1)]. PMID- 3106882 TI - Teaching in the clinic: objectives and style. PMID- 3106883 TI - Three dimensional CT reconstruction for the evaluation and surgical planning of facial fractures. AB - Despite advances in radiology--including CT scanning--the three-dimensional (3D) nature of facial fractures must still be inferred by the spatial imagination of the physician. A computer system (Insight Phoenix Data Systems, Inc., Albany, N.Y.) uses CT studies as substrate for 3D reconstructions. We have used the Insight computer for the evaluation and surgical planning of facial fractures of 16 patients with complex injuries. We present five illustrative cases, directly photographed from the computer monitor. Images can also be manipulated in real time by rotating or planar sectioning (functions best appreciated on video). The ability to cybernetically extract the facial skeleton from living subjects provides precise anatomic data previously unobtainable. The images are valuable for an accurate assessment of the relationship between the injured and uninjured sections of the face. We conclude that 3D reconstruction is an important advance in the treatment of facial fractures. PMID- 3106884 TI - Epithelial-myoepithelial carcinoma of the subglottic region: a case presentation and review of the literature. AB - Epithelial-myoepithelial carcinomas are a rare form of salivary gland carcinoma. They are found predominantly in the parotid glands and rarely occur in the upper airway and in minor salivary glands. These neoplasms are found predominantly in women in the seventh and eighth decades of life and account for less than 1% of all salivary gland ductal carcinomas. These tumors may demonstrate infiltrative and destructive patterns, with a tendency to metastasize. It is recommended that they be approached and treated along the same avenues as any other malignant lesions of the head and neck. PMID- 3106885 TI - Fibromyxoma of the maxilla. PMID- 3106886 TI - Osteomyelitis of the maxilla in a patient with osteopetrosis (Albers-Schonberg disease). PMID- 3106887 TI - Frontal sinus obliteration using liposuction. AB - Frontal sinus obliteration is performed for a variety of reasons, including chronic sinus disease, traumatic injuries, mucoceles, and osteomas of the sinus. Once the decision is made to obliterate the sinus, it is paramount that all mucosal remnants be removed and that the material used to fill the irregular expanses of the frontal sinus help prevent recurrence of the disease process. The materials most commonly used for this purpose are fat, muscle, and pericranium. Fat obtained from the abdomen, gluteal area, or lateral thigh is probably the most frequently used substance. The procurement of fat in the traditional way adds significant time to the operation and is associated with significant morbidity at the donor site. Fat obtained in this manner is often bulky and does not truly conform to the sinus contour. In an attempt to minimize operating time and donor-site morbidity--as well as obtain a more malleable graft--we used liposuction to obtain our fat grafts for sinus obliteration. Using this method, we were able to obtain an adequate amount of tissue from either the abdomen or lateral thigh in all patients. We have used this technique in eleven patients, with follow-ups ranging from 3 to 18 months. We have had no donor-site morbidity and (to date) there has been no recurrence of sinus disease in these patients. While the follow-up period is not adequate for final evaluation in these patients, we believe this is a valuable adjunct to frontal sinus surgery. PMID- 3106888 TI - Evaluation and treatment of frontal sinus fractures. AB - We treated twenty-three patients with blunt or penetrating wounds of the frontal sinus from 1978 through 1983. Nondisplaced anterior wall fractures were observed or explored. Posterior table fractures--with displacement confirmed by computed tomography or polycycloidal tomography--were explored. Either obliteration of the sinus or nasofrontal duct reconstruction with a Sewall-Boyden-McKnaught flap was selected, depending on the magnitude of duct injury. In all cases, the anterior wall was primarily reconstructed. All penetrating wounds with posterior table involvement were treated by cranialization of the frontal sinus and temporalis muscle obliteration of the nasofrontal ducts. Only one case of meningitis occurred, resulting in prolonged hospitalization. PMID- 3106890 TI - Snoring: clinical implications and treatment. AB - Snoring has only recently come under wide study. Recent research has established the close relationship of severe snoring to sleep apnea in terms of the obstructive pathophysiology. Snoring tends to increase in severity over time and may progress to sleep apnea. Severe snoring may be associated with pulmonary and systemic hypertension, secondary polycythemia, and cardiac arrhythmias. PMID- 3106889 TI - Sleep parameters after surgery for obstructive sleep apnea. AB - Obstructive sleep apnea (OSA) is a disorder that is frequently treated surgically. Few reports in the literature give objective reports of the effect of such treatment on polysomnographic parameters before and after treatment, although symptomatic improvement is common. This article reviews total sleep time (TST) spent in apnea, number of apneic episodes per hour or sleep apnea index (SAI), and oxygen desaturations in such patients treated with tracheostomy, uvulopalatopharyngoplasty (UPP), and combinations of these. Although improvement is noted in these parameters after UPP, this is not as impressive as some reports in the literature indicate. Our suggested indications for this type of surgery are discussed. PMID- 3106891 TI - Squamous metaplasia in the trachea: the tracheotomized rabbit as an experimental model and implications in recurrent papillomatosis. AB - Squamous metaplasia following tracheotomy has been well documented. Most studies have dealt primarily with changes at--or adjacent to--the cuff site and have failed to evaluate its effect in the distal trachea. We have used rabbits as experimental models for the induction of tracheal squamous metaplasia, using uncuffed tracheotomy tubes. Rabbits were routinely killed 24, 36, 48, 72, 120, and 168 hours posttracheotomy, and the entire larynx, trachea, and main-stem bronchi were step-sectioned for histologic examination. Patchy areas of squamous metaplasia were found in all rabbits with tracheotomy equal to or longer than 48 hours. The metaplasia appeared to increase with time of intubation. Induction of squamous metaplasia (following tracheotomy as a contributing factor to the spread of laryngeal papillomatosis) is discussed. PMID- 3106893 TI - Infectious croup: a critical review. AB - Infectious croup is a viral or bacterial syndrome characterized by a barking cough, hoarseness, and stridor. Three separate conditions will be discussed: laryngotracheobronchitis, spasmotic croup, and bacterial tracheitis. Each clinical entity will be defined and its treatment reviewed. Current treatment regimens for infectious croup involve various combinations of mist therapy, racemic epinephrine, corticosteroids, and syrup of ipecac. Tradition, rather than science, appears to be the basis of many of these treatments. Despite the frequent occurrence of infectious croup, no treatment has proved consistently successful. Prevention and better treatment methods are the keys for reducing the high cost of infectious croup to the medical care system. PMID- 3106892 TI - Incendiary characteristics of a new laser-resistant endotracheal tube. AB - Endotracheal tube fires are the most frequent complication of laser surgery of the larynx. We investigated the incendiary characteristics of a new laser resistant endotracheal tube, compared to polyvinyl chloride (PVC) and red rubber (RR) tubes, with different gas mixtures. A CO2 laser was focused on each tube and the probability of fire was assessed with oxygen fractions (FiO2) of 30%, 40%, 50%, 70%, and 100%, the balance being N2 or N2O. The laser-resistant tube could not be penetrated by a single laser pulse, regardless of laser energy or gas composition. PVC and RR tubes were readily ignited, the probability of ignition being related to oxygen concentration and laser energy. Nitrous oxide readily supported combustion. We suggest that laser surgery of the larynx can be most safely performed with a laser-resistant endotracheal tube and with gas mixtures containing the minimal safe O2 concentration (without nitrous oxide). PMID- 3106894 TI - Functional electrical stimulation for the treatment of bilateral recurrent laryngeal nerve paralysis. AB - We have previously presented the concept of electrophysiologic pacing of bilaterally paralyzed vocal cord abductors as a solution to the difficult problem incurred in this clinical situation. Initially, we demonstrated that it was indeed feasible to electrophysiologically pace abduction of the vocal cords synchronously with respiration, employing the EMG activity of the diaphragm as a trigger stimulus. Further research has led us to evaluate other possible physiologic trigger stimuli to ascertain which of these will prove most suitable in long-term pacing studies. In this article, we will report our preliminary results, employing negative intrathoracic pressure occurring with respiration--as detected by an implanted pressure transducer as a trigger stimulus. This device was interfaced with a muscle stimulator attached to electrodes placed in the cricoarytenoid muscles in five canines whose recurrent laryngeal nerves had been sectioned bilaterally. In all animals, obvious physiologic synchrony of vocal cord abduction and a reduction of negative inspiratory intratracheal pressure was achieved during electrical pacing. This reinforces our initial findings that it is indeed feasible to pace vocal cord abduction in bilateral recurrent laryngeal nerve paralysis with resultant return of physiologic normality to the glottis. Thus, functional electrical stimulation offers an alternative approach to the difficult problems incurred in the patient with bilateral recurrent laryngeal nerve paralysis. It also demonstrates that physiologic negative intrathoracic pressure activity occurring with inspiration can be a trigger source. PMID- 3106895 TI - Classification of nasal defects: a practical guide for reconstruction. AB - Nasal defects are among the most complicated problems frequently facing the otolaryngologists--head and neck surgeon. The complex role of the nasal structure and its anatomy makes a practical guide for reconstruction particularly attractive. The nose, as a unique facial component, must ideally perform important airway functions, while also having an acceptable appearance. A range of reconstructive problems from simple defects to total nasal loss is addressed. PMID- 3106896 TI - The degree to which accuracy of preoperative staging of laryngeal carcinoma has been enhanced by computed tomography. AB - In this retrospective study, the accuracy of preoperative staging by high resolution CT and clinical evaluation (indirect-direct laryngoscopy) is compared to the postsurgical pathologic staging of laryngeal cancer. Forty-two patients who were admitted to St. Louis University Hospital between the years of 1978 to 1985 with diagnoses of laryngeal cancer were included. All patients received high resolution CT scan of the larynx preoperatively and subsequently underwent total or partial laryngectomy. None of these patients received preoperative radiotherapy. The accuracy of the clinical vs. CT staging--as well as the accuracy of the staging by combination of the two modalities--was determined by comparison with the postsurgical pathologic staging. The accuracy was assessed separately for glottic, supraglottic, and transglottic carcinoma. The accuracy of CT staging for glottic carcinoma was 75%. However, clinical evaluation in this group of lesions was very reliable, offering 92.9% accuracy. The accuracy of CT staging increased in the supraglottic and transglottic lesions, to become superior to the clinical staging. With combined information gained by both examinations, the preoperative staging accuracy was 91.4% for supraglottic carcinoma and 87.5% for transglottic carcinoma. It is, therefore, recommended that high-resolution CT should be included in the preoperative staging of laryngeal cancer. PMID- 3106897 TI - Long-term intracochlear implantation in man. AB - Whether long-term intracochlear implantation and direct electrical stimulation of the acoustic nerve will induce intracochlear bone growth or cause further degeneration of a severely compromised auditory system is an important clinical consideration. Thin-section CT evaluations of the cochleas of six subjects who have used their cochlear implant devices on a daily basis for 3 or more years demonstrated no evidence of osteoneogenesis of the cochlea in the vicinity of the active electrode. No corrosion of the electrode or insulation material was noted on electron microscopy of an explanted electrode system. Electrical threshold and dynamic range measurements have remained stable or even improved during the period of observation. Performance measures using a variety of audiologic tests and speech-tracking scores have demonstrated stability of performance. PMID- 3106898 TI - Thyroid nodules in children. AB - Thyroid nodules are infrequently encountered in children. During the era of low dose therapeutic irradiation, the incidence of malignancy in these lesions was 40% to 70%. Recent studies suggest that this incidence is declining, resulting in a concomitant relative increase in the proportion of benign nodular conditions. There is also a heightened awareness that secondary thyroid neoplasms may occur in children surviving primary malignant diseases. Records of 38 children treated surgically at Texas Children's Hospital between 1972 and 1984 have been reviewed to determine the incidence of benign vs. malignant pathosis and to study the role of prior irradiation or chemotherapy in the pathogenesis of thyroid disease. Benign conditions were diagnosed in 27 children (71%), with diffuse hyperplasia (10 children, 26%) and follicular adenoma (8 children, 21%) occurring most frequently. Thyroid carcinoma was diagnosed in the remaining 11 children (29%). All of these patients were euthyroid at presentation, none had received multimodal therapy for a prior malignant condition, and only one had a history of head and neck irradiation in infancy for a treatment of a benign condition (a congenital hemangioma). The clinical presentation, diagnostic evaluation, and surgical management of these patients are reviewed and closely parallel those of patients in other recently published series. No conclusions can be drawn regarding the development of thyroid neoplasia following multimodal therapy for primary disease; however, this incidence must be very low. PMID- 3106899 TI - Influence of embryonal fusion lines for recurrence of basal cell carcinomas in the head and neck. AB - A reinvestigation of 171 basal cell carcinomas of the head and neck treated by surgical excision revealed 23 recurrences. Recurrence rate in one group of basal cell carcinomas, situated on embryologic fusion lines, was statistically higher than in other groups of basal cell carcinomas situated on other parts of the face and on the capillitium which served as control. Histopathologic subclassification of the recurrent basal cell carcinomas revealed a higher incidence of nodular type with infiltrative margin and of the infiltrative type. Basal cell carcinomas situated in fusion lines tended to grow deeper than in other sites. It was concluded that embryologic fusion lines in the face provide risk zones for spread and recurrence of basal cell carcinomas. Subclassification of basal cell carcinomas should be performed in the routine histopathologic reporting of these neoplasms as a means of predicting recurrence. PMID- 3106900 TI - Magnetic resonance imaging of the head and neck. AB - Magnetic resonance imaging (MR) has already gained wide acceptance in the evaluation of intracranial and spinal canal abnormalities. MR also provides excellent resolution of certain tumors of the head and neck and is particularly useful for the evaluation of neoplasms in the vicinity of the skull base. The absence of a bone signal prevents the streaking artifact so troublesome with computerized axial tomography (CT) and allows better definition of tumor. MR does not use ionizing radiation and appears to be an innocuous imaging mode--thus multiple examinations in young patients are not objectionable with MR. The ability to obtain images in multiple planes by control of the magnetic gradients allows for axial, sagittal, and coronal imaging, without changing the supine position of the patient. Multiple projections are helpful in providing better preoperative assessment of the extent and size of certain neoplasms of the neck. PMID- 3106901 TI - The effect of sterile inflammation on skin flap survival. AB - Several investigations have suggested that a sterile inflammatory reaction in a skin flap enhances flap survival. A chemical peel produces a mild chemical burn, which is one form of nonbacterial inflammatory response. Some authors advocate the concomitant use of face lift and chemical peel, while others caution that the peel might jeopardize the facial flaps. To determine whether the reaction caused by a chemical peel enhances or impairs skin flap survival, a study using miniature pigs was undertaken. Survival length of flaps treated with a chemical peel was compared to that of untreated flaps. A total of 36 dorsally based random flaps were used on three miniature pigs. Six identical 14 X 4 cm flaps were designed on each side of the pigs. A chemical peel was applied to the area of 18 of the proposed flaps 2 days prior to elevation. Alternate flaps on each side of the pigs were treated. As the flaps were elevated, the tips were examined to document the inflammatory response histologically. After 14 days, the surviving length of the flaps was measured. As determined by the Wilcoxon matched-pairs signed-ranks test, there was no significant difference between the treated and untreated groups. Our study shows that a nonbacterial inflammatory response produced by a chemical peel does not improve skin flap survival, at least not in pigs. PMID- 3106902 TI - Computed tomography and the thyroglossal duct cyst. AB - Thyroglossal duct cysts (TDC) classically present as midline neck masses in close relation to the hyoid bone; yet--not uncommonly--their locations may be varied from the midline and from the hyoid. By means of the diagnostic modality of computed tomography (CT), high-resolution images of several cases of alternate presentations and locations of the TDC are examined. Included are examples of TDC in the suprahyoid, transhyoid, infrahyoid, and lateral positions. The potential value of CT in the diagnosis of the unusual cyst will be demonstrated and discussed. PMID- 3106903 TI - Routine use of office endoscopy in otolaryngology. AB - A skilled endoscopist using a flexible fiberoptic nasopharyngolaryngoscope can complete a thorough examination of the upper aerodigestive tract in less time than it takes to heat up a laryngeal mirror. The examination is accomplished with only minimal discomfort for the majority of patients. Consistently clear photographs may be made of the physical findings. The yield, in terms of disease demonstrated and documented, well justifies the routine use of the flexible fiberoptic nasopharyngolaryngoscope on virtually every patient seen for otolaryngologic evaluation. I shall present sixteen examples of pathosis of the upper aerodigestive tract that were overlooked by the traditional means of otolaryngologic examination. All were discovered by the "routine" use of flexible fiberoptic endoscopy. Seven malignant conditions are included. PMID- 3106904 TI - Congenital conductive hearing loss in Apert syndrome. AB - Acrocephalosyndactyly (Apert syndrome) is a rare craniosynostotic syndrome characterized by acrocephaly, syndactyly of the hands and feet, and--occasionally -conductive hearing loss. We report three cases of conductive hearing loss in Apert syndrome. One patient was found to have bilateral stapes fixation. His daughter (the second case) had chronic bilateral otitis media with effusion. The third case involved a fixed incus and hypomobile stapes. The management of these patients and a review of the literature are presented. PMID- 3106905 TI - Middle ear cilia activity as a determinant of tympanostomy tube placement. AB - Three hundred and twenty-six patients with diagnoses of serous otitis media--or mucoid otitis media--were reviewed for the presence or absence of middle ear cilia activity. This study strongly suggests that if active cilia can be observed, ventilating tubes are not needed. This easily observed activity in the anterior-inferior quadrant offers the otolaryngologist an accurate tool for determination of the future health of the middle ear. PMID- 3106906 TI - The state of tinnitus after inner ear surgery. AB - A retrospective study of several procedures--for either treatment of vertigo or resection of acoustic neuromas--was performed to determine their effect on tinnitus. Subjective ratings of the state of tinnitus (resolution, improvement, maintenance, or deterioration) were obtained by questionnaire. Surgical procedures performed for correction of vertigo frequently alter tinnitus. In general, procedures that conserve hearing--namely, retrolabyrinthine vestibular neurectomy (RVN), middle fossa vestibular neurectomy (MFVN), and endolymphatic shunt procedures (ELS)--have a 50% to 65% chance of helping relieve tinnitus and up to a 22% chance of worsening tinnitus. When there is no serviceable hearing, cochleovestibular neurectomy (CVN) offers the best cure rate for tinnitus (76%) and the least chance of worsening tinnitus (3%). When hearing is minimal and the patient complains of tinnitus, a CVN--rather than a labyrinthectomy--should be recommended. However, when useful hearing is present, a CVN is not usually recommended for relief of tinnitus, since the actual cure rates are only 35%. When vertigo is not a complaint, there is currently no surgical procedure known that can be recommended for the treatment of tinnitus. PMID- 3106907 TI - A technique to model the nasal airway for aerodynamic study. AB - This article presents a new technique for creation of a model that can be used to study the aerodynamics of the nasal airway. The model is employed to determine parameters used to calculate nasal resistance and modified to compare various types of nasal obstruction. It quantitatively compares the importance of septal deviation, turbinate size, and nasopharyngeal port size to airflow. A new parameter of nasal resistance is introduced. PMID- 3106908 TI - Otosurgical model in the guinea pig (Cavia porcellus). AB - The guinea pig is a useful model for otologic research. Common problems encountered in working with individual animals include preexisting chronic middle ear disease, anesthetic deaths, and a lack of knowledge of the surgical anatomy and landmarks of the middle and inner ear. The methods detailed in this article will benefit those interested in a reliable, inexpensive, otosurgical animal model. PMID- 3106909 TI - Facial nerve dissection by use of acoustic (loudspeaker) facial EMG monitoring. AB - The development of the surgical microscope in 1953, and the subsequent development of microsurgical instrumentation, signaled the beginning of modern day acoustic neuroma surgery. Preservation of facial nerve function and total tumor removal is the goal of all acoustic neuroma surgery. The refinement of the translabyrinthine removal of acoustic neuromas by Dr. William House significantly improved preservation of facial nerve function. This is made possible by the anatomic identification of the facial nerve at the lateral end of the internal auditory canal. When the surgery is accomplished from a suboccipital or retrosigmoid approach, the facial nerve may be identified at the brain stem or within the internal auditory canal. Identifying the facial nerve from the posterior approach is not as anatomically precise as from the lateral approach through the labyrinth. The use of a facial nerve stimulator can greatly facilitate identification of the facial nerve in these procedures. PMID- 3106910 TI - Calvarial bone grafting of facial defects. AB - Bony defects of the face continue to challenge the reconstructive surgeon. Traditional sources of autologous bone from the rib or pelvis have been associated with the limitations of pain at the donor site, the need for a second operative field, variable "take" of the graft with poor eventual survival and, ultimately, less than optimal reconstruction. Calvarial bone grafting provides a readily accessible source of bone from an inconspicuous donor site, usually within the same operative field. The morbidity is minimal. The calvarial bone graft is especially useful in repair of the frontal sinus, orbital floor, nasal and malar regions, as well as in certain instances of cleft palate with alveolar involvement. PMID- 3106912 TI - Duration of intubation in children with acute epiglottitis. AB - Nasotracheal intubation has been demonstrated to be effective in supporting the airways of children with acute epiglottitis. Length of intubation and criteria used for extubation are still controversial. A 6-year retrospective review at Children's Hospital of Pittsburgh identified 100 cases of acute epiglottitis, which were initially managed with nasotracheal intubation. Extubation was based on direct laryngeal inspection performed in the operating room (1979-1981) and, more recently, in the intensive care unit (1982-1984). Length of intubation decreased from 63.8 hours in 1979 to 42.1 hours in 1984. The percent of children intubated longer than 48 hours decreased from 69% to 22% in the same time period. These data indicate that a shorter period of intubation is aided by daily laryngeal inspection in the ICU. We propose a staging system for acute epiglottitis to aid in the decision to safely extubate these children. PMID- 3106913 TI - Intractable vertigo--when not to operate. AB - Patients with episodic vertigo--or one severe episode of vertigo--may respond to vestibulosuppressive medications or operations on the labyrinth. In patients with constant incapacitating vertigo or disequilibrium, the clinician should suspect nonlabyrinthine disease. A careful history and physical and neurologic examinations will provide clues to underlying disease and direct the selection of further objective tests. PMID- 3106911 TI - Pediatric vestibular evaluation with harmonic acceleration. AB - A group of 101 otologically normal infants and children were evaluated with low frequency harmonic acceleration (HA) to determine the feasibility of use of this procedure in evaluation of vestibular function in a pediatric population. Ninety six of the subjects were successfully tested and normative data are presented. A maturational trend was noted (in the presence of nystagmus) in subjects up to 10 months of age and in the phase-lag measurement up to approximately 4 years of age. PMID- 3106914 TI - CO2 laser management of laryngeal stenosis. AB - The introduction of the carbon dioxide laser as an endoscopic surgical instrument has stimulated interest in its application for removal of stenotic lesions of the larynx. Clinical reports have indicated mixed results in the efficacy of this treatment modality. Nineteen large dogs received acute subglottic injuries from a high-speed electric drill and electrocautery. All animals developed obstructing lesions from 7 to 21 days after injury. With at least weekly removal of granulation tissue and dilations, all animals developed mature subglottic and/or posterior commissure scars. Two animals required tracheostomy. The 15 animals in the experimental group underwent 16 laser procedures. Three animals had vaporization of one third of the scar, three of one half of the scar, and three had total circumferential vaporization. Five animals underwent microtrapdoor flap procedures. Of these, four had a single flap and one had three separate flaps created. In the remaining animal in the experimental group a glottic web developed, which was totally ablated. In one animal treated with a microtrapdoor flap procedure a posterior sinus tract also developed and was treated with laser ablation. The animals undergoing segmental resection of scar demonstrated no improvement in airway size. Those undergoing total resection experienced a worsening of the condition. Those undergoing microtrapdoor flap repair demonstrated moderate improvement in airway size. It can be concluded that large areas of scar removal in the larynx by the CO2 laser will result in prompt recurrence and possible worsening of the scar and smaller submucosal resection of the scar, with preservation of mucosa by the microtrapdoor flap technique, may be helpful in improving the airway. PMID- 3106915 TI - Staple closure of the gullet after laryngectomy: an experimental study. AB - Traditionally, gullet closure that is done after a laryngectomy has been accomplished with tedious and time-consuming suturing procedures. As an alternative to this, staple closure of the gullet has been growing in acceptance and implementation as a mucosal eversion technique. In this article, we shall present several aspects and considerations of this method of surgical closure. PMID- 3106916 TI - Lethal cholesteatoma. AB - Aural cholesteatoma is a disease entity well known to the otologic community. Complications of cholesteatoma, although uncommon, are not usually life threatening. We present two cases in which a unique and hitherto unreported pathway of spread of a cholesteatoma is noted. The cholesteatoma, after originating in the ear, entered the diploe and spread insidiously between the inner and outer tables to distal parts of the skull. Osteomyelitis, in concert with the cholesteatoma, destroyed large areas of the skull in both patients. One patient died of his disease. The other patient was operated on and is alive but has unresectable disease and purulent drainage from three separate cranial fistulas. PMID- 3106917 TI - The otolaryngologist and tetanus. PMID- 3106918 TI - Vestibular responses to pressure variations: a review. AB - A selected review of the literature concerning different forms of pressure stimulation of the normal and abnormal vestibular labyrinth is presented. On the basis of this review, it can be stated that there are definite vestibular signs and symptoms associated with pressure stimulation. The exact mechanisms remain in doubt. The responses, however, appear to be mediated through the vestibular hair cells. PMID- 3106919 TI - A new drape for otolaryngologic laser surgery. PMID- 3106920 TI - Annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. Chicago, Illinois, September 19-23, 1987. 1987 instruction course program. PMID- 3106921 TI - Live oral Salmonella vaccines: potential use of attenuated strains as carriers of heterologous antigens to the immune system. AB - Live attenuated strains of salmonellae are showing promise as live oral vaccines against human typhoid fever and other Salmonella infections of man and animals. Attenuation can be achieved by introducing genetically defined, non-reverting mutations into specific genes on the Salmonella chromosome. Mutations in the gal E or aroA genes of Salmonella inhibit the ability of the bacteria to grow in vivo, and strains carrying such lesions are effective vaccines against salmonellosis. Genetic determinants encoding for the expression of potentially protective antigens from heterologous, non-Salmonella pathogens can be readily introduced into these attenuated Salmonella strains. Expression of the heterologous antigen does not affect the ability of the Salmonella host to be used as a Salmonella vaccine. Mice infected orally with a Salmonella typhimurium aroA vaccine expressing the Escherichia coli heat-labile toxin B subunit developed both a secretory and serum antibody response to this antigen. These serum antibodies were able to neutralise the activity of E. coli heat-labile toxin in tissue culture assays. A humoral and cell-mediated (DTH) immune response was detected against beta galactosidase, an intracellular antigen, in mice infected with an aroA vaccine expressing this cloned antigen. The prospects for the development of live Salmonella vaccines as a method for delivering heterologous antigens derived from bacteria, viruses and parasites is discussed. PMID- 3106922 TI - Activation by synergism between endotoxin and lymphokines of the mouse macrophage cell line J774 against infection by Trypanosoma cruzi. AB - The mouse macrophage cell line J774 was easily infected by T. cruzi epimastigotes which were transformed to amastigotes that multiplied inside the cells. Spleen-T cells from T. cruzi immune mice stimulated with Concanavalin A or T. cruzi, but not with unrelated antigens, released lymphokines into the supernatants that when added to J774 cells were unable to induce complete trypanocidal activity, although they were able to delay the rate of infection by protecting the cells from being infected. Addition of bacterial lipopolysaccharide (LPS), although inactive by itself, acted synergistically with the supernatants in inducing complete trypanocidal activity without affecting the susceptibility of J774 cells to infection. Gamma-interferon (gamma-IFN) activity was detected in the supernatants, however, but was not solely responsible for the trypanocidal inducing activities, since: there was no correlation between the levels of gamma IFN and macrophage activation; gamma-IFN alone was less effective than the supernatants alone; and two active fractions of 100,000-150,000 mol. wt and 30,000 mol. wt were separated by gel filtration chromatography of the lymphokine preparations. The latter, which showed the characteristics of gamma-IFN with respect to size, pH 2 sensitivity and antiviral activity, had some trypanocidal activity alone. However, the 100,000-150,000 mol. wt fraction was active only in the presence of LPS. Finally, this trypanocidal inducing activity of the supernatants was not due to the induction of synthesis of gamma-IFN by the J774 cells. PMID- 3106923 TI - The effect of hydrocortisone, thyroxine, and phenobarbital on diamine oxidase activity in newborn rat intestine. AB - There is a reported association between administration of prenatal glucocorticoids and a decreased incidence of necrotizing enterocolitis in human infants. In rats, the degree of ischemic bowel disease correlates negatively with intestinal diamine oxidase (E.C. 1.4.3.6) activity. Since the administration of hydrocortisone, thyroxine, or phenobarbital to newborn rat pups affects the development of intestinal enzymes, we were interested in knowing whether hydrocortisone, thyroxine, or phenobarbital specifically affect intestinal diamine oxidase activity. We injected rat pups with hydrocortisone sodium succinate, 1-thyroxine pentahydrate, sodium salt, sodium phenobarbital, or the control solution on days 4, 6, 8, or 10 of life (phenobarbital, days 3, 5, 7, or 9). Pups were injected 3 days consecutively (phenobarbital, 4 days), and all were sacrificed on days 7, 9, 11, and 13. Intestinal diamine oxidase and intestinal invertase (E.C. 3.2.1.26) activities were measured. Invertase was used as a control enzyme because it is known to be induced by glucocorticoid hormones. We found that the hydrocortisone-injected pups had 10-fold higher specific activity of invertase than the saline-injected animals. Diamine oxidase activity was significantly higher in the group receiving hydrocortisone and sacrificed on days 7, 9, and 11. Enzyme activity in both the hydrocortisone-injected and saline injected groups was equal on day 13, as was enzyme activity on all days in the thyroxine-injected and sodium hydroxide-injected groups, and the phenobarbital injected and the saline-injected groups. Our results suggest that diamine oxidase activity may be induced by hydrocortisone, but is not affected by thyroxine or phenobarbital. PMID- 3106925 TI - False positivity of Legionella serology in patients with cystic fibrosis. AB - Respiratory deterioration accounts for the morbidity and mortality observed in patients with cystic fibrosis. The role of Legionella in this deterioration was determined in a 2-year prospective study of 49 patients with cystic fibrosis and 19 sibling controls. Sera were obtained from participants on enrollment and at quarterly intervals. Legionella antibodies were measured in parallel using an indirect fluorescent assay. No seroconversions were observed. Eleven of 49 patients with cystic fibrosis (22%) were seropositive compared to none of 19 siblings (P less than 0.05). Six of the 11 patients demonstrated high titers (greater than or equal to 1:512) that persisted throughout the study. Absorption with pools of various Pseudomonas species reduced the antibody titers such that only 3 remained positive after absorption. Legionella was not found to be an important cause of clinical deterioration during this study. The results of the absorption studies suggest that high titers to Legionella in this population are due to cross-reacting antibodies. PMID- 3106924 TI - Taurine concentrations in plasma, blood cells, and urine of children undergoing long-term total parenteral nutrition. AB - Taurine concentrations in plasma, platelets, lymphocytes, granulocytes, erythrocytes, and urine were measured in 19 children who were undergoing long term home parenteral nutrition for 27.4 +/- 7.1 (SEM) months. The parenteral solutions contained methionine, but not taurine or cysteine. The patients' plasma, platelet, and urine taurine concentrations were significantly reduced to 54, 48, and 16%, respectively, of the values from normal children of similar ages. The most significant reductions in plasma and platelet taurine concentrations were observed in the children who were estimated to absorb less than 5% of their daily calorie needs from the enteral tract. Lymphocyte and erythrocyte taurine levels tended to be lower but were not significantly different from those in normal children. The patients' plasma methionine and cystine levels were not different from normal. There was a direct correlation between plasma and platelet taurine concentrations and between plasma and urine taurine. Both plasma and platelet taurine tended to be directly correlated with age and, after the 1st yr of total parenteral nutrition, with the duration of total parenteral nutrition therapy. PMID- 3106926 TI - Early onset neonatal sepsis due to Neisseria meningitidis W135. PMID- 3106927 TI - Effective reduction of lactose maldigestion in preschool children by direct addition of beta-galactosidases to milk at mealtime. AB - We examined the efficiency of two beta-galactosidase preparations--one derived from the yeast, Kluyveromyces lactis (Lactaid), the other derived from the fungus, Aspergillus oryzae (Takamine)--to assist the in vivo digestion of lactose consumed by healthy Guatemalan preschool children. Milk prehydrolyzed by in vitro incubation with enzymes was used as the standard of reference, and the degree of incomplete digestion of lactose from 240 mL of milk was determined using the hydrogen breath test. In in vivo dose-response studies, both 3,250 neutral lactose units of Lactaid and 6,635 food and chemical codex lactose units of Takamine completely eliminated excess H2 excretion in a small sample of lactose maldigesting subjects. When evaluated in a controlled, clinical trial setting, the same dose of Lactaid added directly to the milk at consumption produced an 82% relative reduction in H2 excretion, whereas Takamine was equally as effective as the prehydrolyzed milk. Thus, intraluminal conditions and gastrointestinal transit in the preschool child support the effective assisted digestion of milk lactose in an efficient manner and with the same enzyme to milk ratios as observed previously in adults. PMID- 3106928 TI - The effect of alkaline pH and transmural pressure on arterial constriction and membrane potential of hypertensive cerebral arteries. AB - These studies were undertaken to examine the effect of alkalosis to modify "pressure-induced" activation of isolated cerebral arteries from spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. At pH 7.4 and PCO2 of 34 torr elevation of transmural pressure from 0-140 mm Hg resulted in myogenic activation preceded by membrane depolarization in both SHR and WKY. The degree of developed myogenic tone in SHR was elevated above WKY. Alkalosis (pH 7.4-7.7) depolarized and activated SHR cerebral arteries to a greater extent than WKY. Furthermore, both the electrical and mechanical responses to elevation in transmural pressure were exaggerated in SHR compared to WKY at pH 7.7 (PCO2 constant at 34 torr). Manipulation of PCO2 at constant pH of 7.4 had similar effects on "pressure-induced" myogenic tone in both SHR and WKY. Thus, cerebral arteries from both SHR and WKY depolarize and develop myogenic tone in response to increasing transmural pressure. This response is augmented in SHR, but to a much greater extent upon elevation of extracellular pH, while PCO2 is maintained within normal limits. The implications of these findings are discussed. PMID- 3106929 TI - Molecular analysis of elements inserted into mouse gamma-actin processed pseudogenes. AB - DNA from ten mouse genomic clones, each containing distinct gamma-actin processed pseudogenes, was subjected to electron microscopic heteroduplex analysis, and in three cases (lambda mA36, lambda mA118 and lambda mA119) the heteroduplex formed with the DNA of a reference clone was found to be interrupted by a single stranded loop. The genomic regions corresponding to these loops were subjected to structural analysis and they were found to represent different elements (IEs) inserted into the pseudogenes in a manner that gave rise to short target-site direct repeats. IE 36 (500 base-pairs in length) was found to be an intercisternal A-particle solo long terminal repeat (LTR), a 46 nucleotide region of which had undergone five-fold tandem amplification and subsequent mutation. IE 119 (501 base-pairs in length) was also a solo LTR, bearing similarity to the recently-described GLN-3 class of murine retroviral-like elements. IE 118 (865 base-pairs in length) is repeated 1000-2000 times in the mouse genome. It is not related to any known class of mobile elements, but does possess some sequence motifs that suggest it may be an LTR of a hitherto unrecognized family of retroviral-like elements. It also possesses a 26 out of 27 nucleotide identity to a region of the flanking pseudogene, suggesting that it may have suffered gene conversion. PMID- 3106930 TI - Heat shock loci 93D of Drosophila melanogaster and 48B of Drosophila hydei exhibit a common structural and transcriptional pattern. AB - A comparison of gene structure, sequence, and transcription pattern of heat shock loci 93D of Drosophila melanogaster and 48B of Drosophila hydei has been performed. Both heat shock loci consist of an unique region that is flanked by an internally repetitive element. Different members of these elements are highly conserved, repeat unit length, however, and primary sequence diverged totally. Whereas the overall gene structure in both species is substantially related, sequence conservation is only observed at very few sites in the unique region. These represent primarily sequences that are identified as regulatory elements for faithful transcription and processing. The number and size of transcripts obtained from heat shock locus 48B in third instar larvae closely resembles the pattern of heat shock locus 93D. Thus their quite alike structure and transcription pattern suggest strongly a conserved hitherto unknown function. PMID- 3106931 TI - Structure and expression of the Drosophila calmodulin gene. AB - We have isolated and characterized cDNA and genomic clones representing the calmodulin gene of Drosophila melanogaster. As demonstrated by genomic blots and by reconstruction experiments, the calmodulin gene is represented once in the Drosophila genome. In situ hybridization of cloned probes to the polytene chromosomes of third instar larvae permitted the localization of the gene to region 49A on the left arm of the second chromosome. Two transcripts of 1.65 and 1.9 kb are produced from this gene. The accumulation of calmodulin message was measured at several stages of Drosophila development. The results of these experiments suggest developmental regulation of the gene. Three intervening sequences interrupt the protein coding nucleotides and two of these are located within calmodulin functional domains. The DNA sequence encoding the protein is presented; the derived amino acid sequence is compared to that of other species. The structural similarities of the Drosophila calmodulin gene to calmodulin genes of other species and to other calcium binding protein genes are discussed. PMID- 3106932 TI - The twist gene: isolation of a Drosophila zygotic gene necessary for the establishment of dorsoventral pattern. AB - The twist zygotic gene appears to be involved in the establishment of the dorso ventral pattern in Drosophila embryos. Homozygous twist embryos are partially dorsalized, their gastrulation is abnormal, and they fail to differentiate mesoderm. We determined the temperature-sensitive period of twist around the gastrulation time, and we isolated the gene. A 300 kb chromosomic walk allowed the detection of the 70 kb deletion that delimits the twist region in Df(2R)twiS60. Southern blot analyses of 21 EMS induced twist allele DNAs and systematic Northern blot analyses all over this 70 kb region lead to the localization of the twist gene: within about 10 kb at the left border of the deletion, 2 twist alleles show each a small deletion that uncover a transcription unit whose expression occurs about at the time of gastrulation. PMID- 3106933 TI - Transient formation of DNA strand breaks during the induced differentiation of a human promyelocytic leukaemic cell line, HL-60. AB - During the induced differentiation of the human promyelocytic leukaemic cell line, HL-60, along the myelocytic lineage, DNA strand-breaks are formed. These breaks which are formed in the face of a proficient DNA repair mechanism, are only transiently maintained and subsequently become religated. The ligation of these breaks requires the activity of the nuclear adenosine diphosphoribosyl transferase (ADPRT). Inhibition of nuclear ADPRT, an enzyme totally dependent on the presence of DNA strand-breaks for its activity and required for efficient DNA repair in eukaryotic cells, blocks the religation of these breaks but not their formation. The inhibition of DNA strand ligation in the differentiating HL-60 cells results in loss of viability and cell death. PMID- 3106935 TI - [Economical aspects of diseases of the digestive system]. PMID- 3106936 TI - Costs and benefits in the treatment of duodenal ulcers. PMID- 3106934 TI - DNA repair in human promyelocytic cell line, HL-60. AB - The human promyelocytic cell line, HL-60, shows large changes in endogenous poly(ADP-ribose) and in nuclear ADP-ribosyl transferase activity (ADPRT) during its induced myelocytic differentiation. DNA strand-breaks are an essential activator for this enzyme; and transient DNA strand breaks occur during the myelocytic differentiation of HL-60 cells. We have tested the hypothesis that these post-mitotic, terminally differentiating cells are less efficient in DNA repair, and specifically in DNA strand rejoining, than their proliferating precursor cells. We have found that this hypothesis is not tenable. We observe that there is no detectable reduction in the efficiency of DNA excision repair after exposure to either dimethyl sulphate or gamma-irradiation in HL-60 cells induced to differentiate by dimethyl sulphoxide. Moreover, the efficient excision repair of either dimethyl sulphate or gamma-irradiation induced lesions, both in the differentiated and undifferentiated HL-60 cells, is blocked by the inhibition of ADPRT activity. PMID- 3106938 TI - Assessment of TRH as a potential MSH release stimulating factor in Xenopus laevis. AB - This study considers the possible involvement of the tripeptide TRH (thyrotropin releasing hormone) in the physiological regulation of melanophore stimulating hormone (MSH) secretion from the pars intermedia of the toad, Xenopus laevis. TRH was shown to stimulate release of MSH from superfused neurointermediate lobes obtained from white-background adapted animals, but had no effect on secretion from lobes of black-background adapted animals. Immunohistochemical analysis revealed a rich TRH-containing neuronal network terminating in the neural lobe of the Xenopus pituitary. Plasma levels of TRH, determined with a specific radioimmunoassay, proved to be extremely high and no significant difference in this level could be found between white- and black-adapted animals. Plasma TRH probably originates from the skin, and our results show that its concentration is within the effective concentration range established for this peptide in stimulating MSH release from the pars intermedia. Therefore, while both our superfusion and immunohistochemical results argue favourably for a function of TRH in the regulation of MSH secretion, we conclude that, in any regulatory role, it would likely have to function within the pars intermedia at concentrations exceeding the high plasma values. While TRH could be involved in short-term activation of the secretory process in white-background adapted animals or in animals undergoing the initial stages of black background adaptation, our results indicate that this peptide may have no function in the maintenance of secretion from the pars intermedia of animals fully adapted to black background. PMID- 3106937 TI - Vasoactive intestinal peptide stimulates plasminogen activator activity by cultured rat granulosa cells and cumulus-oocyte complexes. AB - Vasoactive Intestinal Peptide (VIP), originally considered to be a gut hormone, has recently been found to increase estrogen and progesterone production by ovarian granulosa and luteal cells. Because several studies indicate that granulosa cells and oocytes are capable of producing plasminogen activators, we have studied the effects of VIP on plasminogen activator activity in cultured granulosa cells and cumulus-oocyte complexes collected from the ovaries of hypophysectomized, estrogen-treated immature rats. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by a fibrin overlay technique to assess plasminogen activator activity, we observed that treatment with VIP stimulated the secretion of tissue-type plasminogen activator (tPA), but not urinary-type plasminogen activator (uPA), in a dose-dependent manner by cultured granulosa cells as well as by cumulus-oocyte complexes, but not by denuded oocytes. However, preparation of cumulus-free oocytes from cumulus-oocyte complexes which had previously been treated with VIP indicated substantial increases in tPA activity within the oocyte. The actions of VIP on tPA activity in granulosa cells were specific, because other closely related peptides (PHM-27 and glucagon) were ineffective. These effects of VIP, in addition to the previously observed effects on steroidogenesis, suggest that VIP may be an important regulator of ovarian function. PMID- 3106939 TI - [Congenital diverticulum of the duodenum]. PMID- 3106940 TI - Home parenteral nutrition and the family. AB - When a patient begins home parenteral nutrition (HPN), everyone in the patient's family is affected. In the early stages, the predominant issues are unfamiliarity with the HPN equipment and fear of acute complications. Later, adjustments become necessary in routine family activities such as eating, traveling, and recreation. The indwelling catheter used for parenteral feeding is a source of body-image distortion and anxiety for the patient, his or her sexual partner, and family members in general. The role of the consultation-liaison psychiatrist in the multidisciplinary home hyperalimentation team is described. PMID- 3106941 TI - The effect of some flavonoids on non-enzymatic lipid oxidation and enzymatic oxidation of arachidonic acid. AB - Twenty flavonoids isolated from plants or transformed into methyl or acetyl derivatives were tested with regard to their influence on cyclooxygenase from the ram seminal vesicle microsomes and lipoxygenase from soya beans. Moreover, their antioxidant properties were evaluated by estimating the amount of the malonylaldehyde formed from arachidonic acid. Only rhamnetin and myricetin inhibited the soybean lipoxygenase. Most of the tested flavonoids stimulated cyclooxygenase at a high (100 microM) substrate concentration, myricetin being the most potent. Rhamnetin was the strongest antioxidant, while myricetin was about ten times weaker. Structural requirements for the cyclooxygenase stimulation, lipoxygenase inhibition and antioxidant properties were different in the case of the twenty tested flavonoids. PMID- 3106943 TI - [Endodontic treatment and the chairside assistant]. PMID- 3106942 TI - Avascular nonunion of a subtrochanteric femur fracture with formation of a heterotopic bone strut. A case report. AB - Comminuted, subtrochanteric fractures of the femur are a complex and challenging form of skeletal injury. Reconstruction and fixation are technically demanding, and fracture nonunion is a known complication of both surgical and closed treatment. A case of an avascular nonunion in a subtrochanteric femur fracture with an interesting resolution is reported. PMID- 3106944 TI - [Professional activity and eye lesions]. PMID- 3106945 TI - [Indications for compiling the periodontal chart]. PMID- 3106946 TI - [Disinfection and sterilization in the dental office]. PMID- 3106947 TI - [Hepatic cytochrome P-450]. PMID- 3106948 TI - A differential response in turkey poults to various antibiotics in diets designed to be deficient or adequate in certain essential nutrients. AB - Two experiments, each consisting of two trials, were conducted with day-old Nicholas Large White turkey poults to compare the effectiveness of four antibiotics for growth promotion and the utilization of sulfur amino acids. A corn-soybean meal basal diet that contained no supplemental methionine, choline, or inorganic sulfate was used in order to furnish nutritional stress. The diet was calculated to contain 25.4% protein, .448% methionine, .403% cystine, 1014 mg/kg choline, and 2990 kcal metabolizable energy/kg. In Experiment 1, a 2 X 4 factorial arrangement of treatments was used. This included two levels, (0% (control) and .18%), of supplemental DL-methionine and no antibiotic or bacitracin MD, flavomycin, or virginiamycin; antibiotics were fed at 50, 2, and 20 g/ton, respectively. In Experiment 2, lincomycin also was included as a treatment (at 4 g per ton) resulting in a 2 X 5 factorial arrangement of treatments. Only the addition of Virginiamycin to the control diet in Experiment 1 resulted in significantly increased body weights. Supplementation by .18% methionine increased body weights and feed efficiency. In addition, all three antibiotics increased body weights significantly when added to the .18% methionine diets. Feed efficiency values were improved by all four antibiotics at both methionine levels. In Experiment 2, increases in body weights similar to those in Experiment 1 were obtained with the addition of .18% methionine to the basal diets. Addition of lincomycin and virginiamycin improved body weights and feed efficiencies in the presence and absence of supplemental methionine. PMID- 3106949 TI - Influence of orally administered thyrotropin-releasing hormone on plasma growth hormone, thyroid hormones, growth, feed efficiency, and organ weights of broiler chickens. AB - Thyrotropin-releasing hormone (TRH) was administered continuously or intermittently in the drinking water of male broiler chickens from 2 to 21 days of age. Intermittent administration of TRH was accomplished by giving birds access to the solution for 2 hr, then removing it for 2 hr, with six repetitions of this procedure each 24 hr. The TRH concentration was such that the birds each would ingest 10 to 20 micrograms of the material during each 2-hr period that it was available. Plasma growth hormone (GH) levels were elevated within 30 min after an episode of TRH administration at 2, 7, and 14 days of age but not at 21 days. Continuous administration of TRH had no effect on GH in plasma at any age. Thyroxine concentrations in plasma were increased within 30 min of first exposure to TRH at 2 days of age, but they were unaffected by intermittent episodes of TRH at 7, 14, and 21 days of age. Triiodothyronine concentrations in plasma were unaffected by TRH at any age. Even though intermittent TRH administration elicited significant elevation in plasma GH for at least 14 days of the experiment, it had no effect on body weight, feed consumption, or weight of the gastrocnemius muscle, the pectoralis major muscle, liver, tibia, or abdominal fat pad. PMID- 3106950 TI - [Comparison of the anti-allergic and anti-asthmatic effects of SM 857 (Doqualast) and DNCG]. PMID- 3106951 TI - [Kinetic study of 3,4-dihydroxyphenyl-L-alanine synthesis in Citrobacter freundii cells immobilized in carrageenan]. AB - A kinetic study was carried out of the enzymatic synthesis of 3,4-dihydroxyphenyl L-alanine (DOPA) by the Citrobacter freundii 62 cells, possessing tyrosine-phenol lyase (TPL) activity, immobilized in carrageenan, and optimum conditions of the reaction were found. The dependence of the TPL activity and its stability on the conditions of the DOPA synthesis was investigated. The TPL activity was higher and more stable in the immobilized cells as compared to free ones. PMID- 3106952 TI - [Electrochemical immobilization of glucose oxidase in the polyacrylamide coating in the presence of glutaraldehyde]. AB - A new electrolyte composition for preparing polyacrylamide coatings with immobilized glucose oxidase that contains glutaraldehyde as a component is proposed. The polarographic behaviour of glutaraldehyde at increased ZnCl2 concentrations answers the criterion of electrochemical polymerization. Glutaraldehyde improves cross-linkage within polyacrylamide, provides an increase of the coating mass and its better quality and adherence, as well as the covalent binding of the enzyme during electrochemical immobilization. PMID- 3106953 TI - [Immunologic method of predicting the tuberculosis process]. PMID- 3106954 TI - [Nutrient media for cultivating Mycobacterium tuberculosis]. PMID- 3106955 TI - [Potentiating the specific activity of isoniazid and streptomycin by benzimidazole derivatives]. PMID- 3106956 TI - Sarcocystis mucosa (Blanchard 1885) Labbe 1889 in unadorned rock wallabies (Petrogale assimilis) and Bennett's wallabies (Macropus rufogriseus). AB - Macroscopic cysts of a protozoan parasite were detected in the gastro-intestinal walls of two unadorned rock wallabies (Petrogale assimilis) and 20 Bennett's wallabies (Macropus rufogriseus). The cysts were located predominantly in the muscularis externa and the submucosa of the forestomach, small intestine and colon and sometimes in the muscularis externa of the oesophagus and caecum. All cysts exhibited similar morphological and ultrastructural characteristics. They were bounded by thick primary cyst walls (containing distinctive bulbous-like protrusions) and were surrounded by collagen fibres and host connective tissue cells (mainly fibrocytes). The cysts were divided by septae into internal compartments containing metrocytes and cystozoites. The cystozoites contained numerous organelles typical of apicomplexan protozoan parasites (including an apical complex, a micropore, rhoptries, micronemes, polysaccharide granules and 22 subpellicular microtubules) and they were observed to divide by the process of endodyogeny. Despite the unusual location of the cysts, they were classified on the basis of their ultrastructural characteristics as Sarcocystis mucosa (Blanchard 1885) Labbe 1889. PMID- 3106957 TI - An enzyme linked immunosorbent assay to diagnose Babesia bovis infection in cattle. AB - The optimum gel filtration fraction from lysate of Babesia bovis infected erythrocytes was determined for use as an antigen in an ELISA to diagnose B. bovis infection in cattle. Of four enzyme labels tested, horseradish peroxidase was the most suitable. The assay is both sensitive and specific in detecting antibody for 2-4 years after a single infection. False positive reactions were obtained only with some sera from some Anaplasma marginale infected cattle. PMID- 3106958 TI - Antibodies to laminin in Trypanosoma rangeli-infected subjects. PMID- 3106959 TI - Combined effects of alpha-difluoromethylornithine and doxorubicin against pancreatic cancer cell lines in culture. AB - Pancreatic adenocarcinoma presents a clinical and experimental challenge because of its relative resistance to conventional modes of therapy. The present study explores a novel, biologically based approach to enhancing its chemosensitivity and to overcoming its chemoresistance in a panel of pancreatic adenocarcinoma cell lines (two human lines: PANC-1 and COLO-357; and two hamster lines: WD PaCa and PD PaCa). Difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase (ODC) that produces antiproliferative effects by polyamine depletion, was combined with the cytotoxic agent doxorubicin (DOX) in vitro. The inhibitory effects of DFMO were cytostatic and roughly additive to those of DOX. Although the response to the combination varied as a function of the cell lines studied and the response to DFMO as a single agent, all cell lines studied showed some increased inhibition with the combination. The most striking enhancement was seen in our most DOX-resistant cell line, WD PaCa, and also in PANC-1, a relatively sensitive cell line. Thus, the combination of DFMO and DOX shows promise as an experimental approach to the problem of drug resistance and the limited chemosensitivity of pancreatic cancer. PMID- 3106960 TI - Characteristics of L-glutamine transport in the perfused rat exocrine pancreas: lack of sensitivity to insulin and streptozotocin-induced experimental diabetes. AB - The transport specificity of L-glutamine influx in the perfused rat exocrine pancreas has been investigated using a dual isotope tracer dilution technique. During a single circulation through the isolated pancreas, an epithelial uptake of 71 +/- 1% (n = 10) was measured for L-(3H)glutamine relative to the extracellular marker D-(14C)mannitol. L-(3H)glutamine uptake was markedly inhibited during perfusion with 10 mM L-glutamine, L-histidine, L-methionine, L serine, or L-cysteine. The system A--specific analogue alpha methylaminoisobutryic acid and L-glutamic acid were ineffective inhibitors. L Glutamine transport was saturable (0.05 - 32 mM), with an apparent Kt = 14 +/- 1 mM and Vmax = 13.4 +/- 0.7 mumol/min g (n = 6), and largely insensitive to perfusion with 1 mM ouabain or a sodium-free solution. In kinetic inhibition experiments, the Vmax/Kt ratio for L-glutamine remained unaltered during perfusion with 10 mM L-serine, whereas L-glutamine appeared to inhibit L-serine transport noncompetitively. Tracer L-glutamine efflux was enhanced by increasing concentrations of unlabeled L-glutamine and 10 mM L-serine. Similarly, tracer L serine efflux was accelerated in the presence of 10 mM L-glutamine. Unlike L serine, the transport activity for L-glutamine was not stimulated by 100 microU/ml exogenous insulin or streptozotocin-induced experimental diabetes. These findings suggest that in the exocrine pancreas, L-glutamine transport is mediated primarily by a large neutral system L. PMID- 3106961 TI - Deduced amino acid sequence of bovine retinal Go alpha: similarities to other guanine nucleotide-binding proteins. AB - A bovine retinal cDNA clone encoding the complete sequence (354 amino acids) of Go alpha, a guanine nucleotide-binding protein (G protein), was isolated by using oligonucleotide probes complementary to published sequences in two putative clones for the alpha subunit of bovine transducin (T alpha). The deduced amino acid sequence contained sequences identical to those in seven tryptic peptides (total 63 amino acids) from bovine brain Go alpha. The cDNA for bovine retinal Go alpha exhibits greater than 90% identity in both coding and 3' untranslated regions with a recently described partial cDNA clone for Go alpha from rat brain [Itoh, H., Kozasa, T., Nagata, S., Nakamura, S., Katada, T., Ui, M., Iwai, S., Ohtsuka, E., Kawasaki, H., Suzuki, K. & Kaziro, Y. (1986) Proc. Natl. Acad. Sci. USA 83, 3776-3780]. Comparison of the nucleotide and deduced amino acid sequences of the bovine Go alpha clone with those previously reported for other G proteins of bovine origin (Gs alpha, Gi alpha, and T alpha) reveals extensive regions identical to those surrounding the amino acids modified by cholera toxin and pertussis toxin. There are also marked similarities of sequence in regions of the G proteins, elongation factors, and the ras p21 gene products that are believed to be involved in guanine nucleotide binding and GTP hydrolysis. PMID- 3106962 TI - Reaction of argininosuccinase with bromomesaconic acid: role of an essential lysine in the active site. AB - We have undertaken studies on bovine liver argininosuccinase (L-argininosuccinate arginine-lyase, EC 4.3.2.1) with the active site-directed reagent bromo[U 14C]mesaconic acid, an analogue of fumaric acid. Reactivity, measured by enzyme inactivation, followed pseudo-first-order kinetics, and the rate increased with reagent concentration. Argininosuccinate completely protected the enzyme against inactivation, but neither arginine nor fumarate was protective. A plot of the degree of inactivation as a function of alkyl groups incorporated was extrapolated to 4 mol per mol of enzyme, or 1 mol per active site. After large scale alkylation of the enzyme (and digestion with trypsin), two 14C-labeled tryptic peptides were isolated. These were chemically sequenced by the Edman method. The amino acid sequences proved to be identical with regions of the deduced amino acid sequences or argininosuccinases from human and yeast sources [O'Brien, W. E., McInnes, R., Kalumuck, K. & Adcock, M. (1986) Proc. Natl. Acad. Sci. USA 83, 7211-7215; Beacham, I. R., Schweitzer, B. W., Warrick, H. M. & Carbon, J. (1984) Gene 29, 271-279]. The 14C-labeled tryptic peptide in the active site region had the sequence Gly-Leu-Glu-Xaa-Ala-Gly-Leu-Leu-Thr-Lys; Xaa represents an unknown phenylthiohydantoin derivative detected in cycle 4. The corresponding amino acid was identified as lysine-51 on the basis of sequence similarity with human and yeast amino acid sequences in this region. The reaction of the enzyme with the alkylating agent and the specific protection against inactivation by argininosuccinate suggest that this lysine residue has an essential role in the binding of argininosuccinate to the enzyme and, consequently, is essential for catalysis. PMID- 3106963 TI - Purification, properties, and immunocytochemical localization of human liver peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase. AB - A molecular understanding of genetic disease in which peroxisomal functions are impaired depends on analysis of the structure of normal and mutant enzymes of peroxisomes. We report experiments describing the isolation, characterization, and immunocytochemical localization of enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme (PBE) of the peroxisomal fatty acid beta oxidation system from normal human liver and compared it with that of rat liver enzyme. The human enzyme, purified approximately equal to 2300-fold by ion exchange chromatography, is homogeneous as judged by NaDodSO4/PAGE. This PBE is localized exclusively in the matrix of peroxisomes in liver cells by the protein A/gold immunocytochemical method. The human PBE is similar to rat enzyme in size (Mr, approximately equal to 79,000), isoelectric point (pI, 9.8), pH optima, molecular structure as observed by rotary shadowing, and peptide pattern on NaDodSO4/PAGE after proteolytic digestion with Staphylococcus aureus V8 protease. The human and rat enzymes differed in their immunological properties by having partial identity with each other; this is reflected in their slightly dissimilar composition of the amino acids aspartic acid, threonine, glutamic acid, tyrosine, and glycine. COOH-terminal amino acid were similar for both the enzymes: -Gly-Ser Leu-Ile-COOH. These results suggest that the human and rat liver PBE may be different in their amino acid sequences at their antigenic sites. PMID- 3106964 TI - Coinduction of glucose-regulated proteins and doxorubicin resistance in Chinese hamster cells. AB - The glucose-regulated protein (GRP) system in mammalian cells is induced by glucose deprivation, anoxia, the calcium ionophore A23187, and 2-deoxyglucose. In Chinese hamster ovary cells the major GRPs are approximately equal to 76, 97, and 170 kDa. Removal of each of these four GRP-inducing stresses leads to the coordinate repression of GRPs and induction of the major heat shock proteins at 70 and 89 kDa. The application of each of these four GRP-inducing conditions leads to a significant induction of resistance to the drug doxorubicin. Removal of each GRP-inducing condition results in the rapid disappearance of this resistance in a manner that correlates with the repression of the GRPs. The retention of doxorubicin by GRP-induced cells does not explain the induced drug resistance. When the RIF in vitro/in vivo tumor system is probed with an antibody against the 76-kDa GRP, a significant increase in this GRP is observed in cells obtained from the central regions of tumors. Since hypoxia and/or nutrient deprivation can occur during tumor development, a GRP-induced state in the tumor may confer resistance to doxorubicin treatment. PMID- 3106965 TI - A molecular phylogeny of the hominoid primates as indicated by two-dimensional protein electrophoresis. AB - A molecular phylogeny for the hominoid primates was constructed by using genetic distances from a survey of 383 radiolabeled fibroblast polypeptides resolved by two-dimensional electrophoresis (2DE). An internally consistent matrix of Nei genetic distances was generated on the basis of variants in electrophoretic position. The derived phylogenetic tree indicated a branching sequence, from oldest to most recent, of cercopithecoids (Macaca fascicularis), gibbon-siamang, orangutan, gorilla, and human-chimpanzee. A cladistic analysis of 240 electrophoretic characters that varied between ape species produced an identical tree. Genetic distance measures obtained by 2DE are largely consistent with those generated by other molecular procedures. In addition, the 2DE data set appears to resolve the human-chimpanzee-gorilla trichotomy in favor of a more recent association of chimpanzees and humans. PMID- 3106966 TI - Molecular cloning and characterization of esterase-6, a serine hydrolase of Drosophila. AB - The Est-6 gene of Drosophila melanogaster was cloned by screening libraries with synthetic oligonucleotides corresponding to tryptic peptides from purified esterase-6 (Est-6) protein. cDNA clones were isolated that hybridized in situ to the site of Est-6 on chromosome 3 at 69A1. Inserts in putative Est-6 cDNA clones were 1.85 kilobases (kb) long, and blot hybridization analysis of electrophoretically fractionated RNA, using a cDNA clone as a probe, revealed two transcripts, of 1.68 and 1.83 kb. The two transcripts showed the same developmental profile as the Est-6 protein. Neither transcript was detected in an Est-6-null line. The cDNA fragment was homologous to a 2.3-kb EcoRI-BamHI fragment in genomic clones, and this region was interrupted by the 8-kb B104 transposable element in the Est-6-null line. Conceptual translation of the cDNA sequence revealed a protein of 548 residues with 19% sequence similarity to acetylcholinesterase from the Torpedo ray. PMID- 3106967 TI - Regulation of murine class I genes by interferons is controlled by regions located both 5' and 3' to the transcription initiation site. AB - Interferons regulate the expression of a large number of mammalian genes, including the major histocompatibility antigen genes. To investigate the mechanisms involved in interferon action, we have analyzed the ability of murine H-2Ld and H-2Dd DNA sequences to control the responses to interferon. The results indicate that interferon regulation of class I gene expression is complex and involves at least two mechanisms that are dependent on class I sequences located upstream and downstream to the transcription initiation site. In transfected mouse L cells, both of these regions are required for full enhancement of class I gene expression, with the major portion of the response controlled by the sequences located 3' to the transcription initiation site. The fine-mapping analysis of the 5' region-encoded response also suggests that recombinant alpha and gamma interferons may exert their effects on class I gene expression by using different cis-acting regulatory sequences. PMID- 3106968 TI - Interferon gamma induces lung colonization by intravenously inoculated B16 melanoma cells in parallel with enhanced expression of class I major histocompatibility complex antigens. AB - Treatment of H-2-deficient nonmetastatic B16 melanoma cells with physiological doses of interferon gamma (IFN-gamma) reduced cellular growth in vitro but induced a shift to the lung-colonizing phenotype as assessed after intravenous injection of the treated cells. As little as 1 antiviral unit of recombinant IFN gamma per ml induced B16 cells to form 3-40 pulmonary metastases in each injected mouse, whereas a 1000-fold higher concentration of IFN-beta was required to see similar effects. IFN-gamma may induce cell-surface molecules that contribute to the metastatic ability of the tumor cells. The efficient enhancement of metastatic ability after IFN-gamma treatment of the B16 cells was paralleled by an increased H-2 antigen expression and decreased sensitivity to natural killer cells. The experiments support the idea that metastasis may not depend exclusively on stable genetic changes or heterogeneity within a tumor population but may be also influenced through the modulation of the phenotype by physiological or pharmacological agents. The results are also discussed with regard to the role of different effector cells in tumor cell clearance and in relation to lymphokine-based strategies for therapy. PMID- 3106969 TI - Recognition of Alzheimer paired helical filaments by monoclonal neurofilament antibodies is due to crossreaction with tau protein. AB - Neurofibrillary tangles and senile plaques are the principal pathological features of Alzheimer disease. Neurofibrillary tangles and the neurites of senile plaques contain paired helical filaments (PHF) that consist of two 10-nm filaments twisted into a double helix. The precursor proteins of PHF are not fully known. To identify these precursors, numerous immunochemical studies have been carried out during the past decade. Two apparently conflicting results have been reported. (i) Some, but not all, monoclonal antibodies to neurofilaments stained neurofibrillary tangles. (ii) Polyclonal antibodies prepared to PHF purified in NaDodSO4 because of their unusual insolubility did not recognize normal proteins, including neurofilaments, on electrophoretic transfer blots of human brain homogenates. These results have been confirmed in several laboratories, including by the use of electron microscopic labeling. Recently, we reported that polyclonal PHF antibodies include antibodies to tau proteins, a family of heat-stable microtubule-associated phosphoproteins, and that antibodies to tau stain Alzheimer neurofibrillary tangles. Those monoclonal neurofilament antibodies that recognize tangles are reported to be directed against phosphorylated epitopes. These facts prompted us to reexamine certain neurofilament monoclonal antibodies that stain neurofibrillary tangles. All monoclonal neurofilament antibodies that stain tangles that we examined, including those initially reported, reacted with tau proteins. Our results suggest that these antibodies react with phosphorylated tau proteins in PHF, not neurofilament proteins, highlighting the problem of using antibodies to phosphorylated protein epitopes in immunochemical studies. Independent evidence for the presence of neurofilament proteins in human paired helical filaments is now required. PMID- 3106970 TI - Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells. AB - A chimeric mouse-human antibody has been created that recognizes an antigen found on the surface of cells from many carcinomas. Immunoglobulin constant (C) domains of the mouse monoclonal antibody L6, C gamma 2a and C kappa, were substituted by the human C gamma 1 and C kappa by recombining cDNA modules encoding variable or C domains. The cDNA constructs were transfected into lymphoid cells for antibody production. The chimeric antibody and mouse L6 antibody bound to carcinoma cells with equal affinity and mediated complement-dependent cytolysis. In the presence of human effector cells, the chimeric antibody gave antibody-dependent cellular cytotoxicity at 100 times lower concentration than that needed for the mouse L6 antibody. The chimeric antibody, but not the mouse L6 antibody, is effective against a melanoma line expressing small amounts of the L6 antigen. The findings point to the usefulness of the chimeric antibody approach for obtaining agents with strong antitumor activity for possible therapeutic use in man. PMID- 3106971 TI - Cholinergic phosphatidylinositol modulation of inhibitory, G protein-linked neurotransmitter actions: electrophysiological studies in rat hippocampus. AB - In electrophysiological studies using the rat hippocampal slice preparation, cholinergic agonists and phorbol 12,13-diacetate, a stimulator of protein kinase C, block the inhibitory actions of baclofen, a gamma-aminobutyric acid B receptor agonist, and adenosine. Relative potencies of cholinergic agonists in stimulating the phosphatidylinositol system, as measured biochemically, parallel their activity in blocking adenosine assessed electrophysiologically. Electrical stimulation of cholinergic afferents also reverses adenosine's inhibitory action. These findings indicate that stimulation of protein kinase C by the phosphatidylinositol system mediates cholinergic blockade of adenosine and baclofen. As these inhibitory agonists act by way of receptors linked to GTP binding proteins, protein kinase C's inactivation of the GTP-binding protein involved may account for this cholinergic action. PMID- 3106972 TI - Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells. AB - Human granulosa cells cultured with calf serum actively proliferated for 18-20 generation and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and alpha inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin. PMID- 3106973 TI - Metallothionein genes in Drosophila melanogaster constitute a dual system. AB - We have selected a metallothionein (MT) cDNA clone from a cadmium-resistant Drosophila melanogaster cell line. This clone includes an open reading frame coding for a 43-amino acid protein whose characteristics are a high cysteine content (12 cysteines, 28% of all residues) and a lack of aromatic amino acids. This protein differs markedly from the Drosophila MT (Mtn gene) previously reported [Lastowski-Perry, D., Otto, E. & Maroni, G. (1985) J. Biol. Chem. 260, 1527-1530). The MT system of Drosophila thus consists of at least two distantly related genes, in sharp contrast with vertebrate MT systems, in which the different members of MT gene families display high similarity. The gene corresponding to our MT cDNA (Mto) is inducible in Drosophila cell lines and in both larval and adult flies. PMID- 3106974 TI - Relocation of a protease-like gene segment between two retroviruses. AB - An anomalous sequence in certain lentiviruses was found to be related to a region in a completely different part of the simian retrovirus type I (SRV-I) and its close relative, the hamster intracisternal A particle (IAP-H18). The segment is not present in the human immunodeficiency virus (HIV), which is also a lentivirus, nor is it found in any one of a dozen other retroviruses whose sequences have been reported. These observations imply that a horizontal transfer of newly acquired genetic information has taken place between an SRV-I-type virus and one of the lentivirus type, and that this event occurred more recently than did the divergence of members of this latter group and HIV. Comparison of the viral nucleic acid sequences that encode these segments revealed the presence of imperfect direct nucleotide repeats resembling the retroviral endonuclease cleavage sites at the 5' and 3' ends of these regions. PMID- 3106976 TI - N-terminal methionine-specific peptidase in Salmonella typhimurium. AB - Crude extracts of a multiply peptidase-deficient strain of Salmonella typhimurium contain an aminopeptidase that specifically removes N-terminal methionine from peptides. This activity shows pronounced specificity for the peptide's second amino acid. Methionine is removed from peptides with alanine, threonine, or glycine in this position but not when the second amino acid is leucine or methionine. The activity is stimulated by Co2+ and is inhibited by EDTA. Mutations that lead to overproduction (up to 30-fold) of the activity have been obtained by selecting for growth on Met-Gly-Gly as a methionine source. These mutations map at approximately 3 map units, phage P22 cotransducible with leu. The overproducer mutations are dominant to wild type, and duplication of the wild type allele of the locus leads to a gene dosage effect on peptidase levels. This suggests that the locus of the overproducer mutations may be the structural gene for the peptidase. NaDodSO4/PAGE shows an increased level of a single protein (34 kDa) in the overproducer mutant. This protein is highly enriched in a purified preparation of the peptidase. The specificity of this enzyme suggests that it is involved in the cleavage of methionine from newly synthesized peptide chains. This activity can specifically remove methionine from the N terminus of a completed protein. Treatment of purified, unprocessed (N-terminal methionine) interleukin 1 beta with the purified peptidase results in removal of N-terminal methionine with no additional alterations. N-terminal processing of at least this protein can occur after translation is complete. We propose to call this enzyme peptidase M (methionine-specific aminopeptidase). PMID- 3106975 TI - Purification and characterization of yeast myristoyl CoA:protein N myristoyltransferase. AB - Myristoyl CoA:protein N-myristoyltransferase (NMT) catalyzes the addition of myristic acid to the amino-terminal glycine residues of a number of eukaryotic proteins. Recently, we developed a cell-free system for analyzing NMT activity and have begun to characterize the substrate specificity of this enzyme by using a series of synthetic peptides. We have now purified NMT from Saccharomyces cerevisiae to apparent homogeneity. The native enzyme is a 55-kDa protein, exhibits no requirement for divalent cation, and appears to contain a histidine residue critical for enzyme activity. A total of 42 synthetic peptides have been used to define structure/activity relationships in NMT substrates. An amino terminal glycine is required for acylation; substitution with glycine analogues produces peptides that are inactive as substrates or inhibitors of NMT. A broad spectrum of amino acids is permitted at positions 3 and 4, while strict amino acid requirements are exhibited at position 5. Replacement of Ala5 in the peptide Gly-Asn-Ala-Ala-Ala-Ala-Arg-Arg with Asp ablates the peptide's myristoyl accepting activity. A serine at this position results in a decrease by a factor of approximately equal to 500 in the apparent Km in the context of three different sequences. Penta- and hexa-peptides are substrates, but with decreased affinity. These studies establish that structural information important for NMT ligand interaction exists beyond the first two amino acids in peptide substrates and that the side chains of residue 5 play a critical role in the binding of substrates to this enzyme. PMID- 3106977 TI - Kinesin is associated with a nonmicrotubule component of sea urchin mitotic spindles. AB - Sea urchin embryos in second division have been lysed into microtubule stabilizing buffers to yield mitotic cytoskeletons (MCSs) that consist of two mitotic spindles surrounded by a cortical array of filaments. Microtubules have been completely extracted from MCSs by incubation at 0 degrees C with Ca2+ containing buffer. An antibody to the microtubule translocator kinesin stains the spindles in MCSs and in MCSs treated with 5 mM ATP and also stains spindle remnants of the MCSs after the microtubules have been extracted. We conclude that kinesin binds to a nonmicrotubule component in the mitotic spindle. Based on these results, we present several models of kinesin function in the spindle. PMID- 3106978 TI - Cloning and characterization of a dispersed, multicopy, X chromosome sequence in Drosophila melanogaster. AB - We have isolated and characterized a dispersed middle repetitive DNA sequence from Drosophila melanogaster that is concentrated on the euchromatic portion of the X chromosome. In situ hybridization of the repeat unit to salivary gland chromosomes shows the sequence is distributed among approximately 10 major and 20 minor X chromosomal sites. Based on DNA sequence analysis of homologous sequences from three different cytogenetic regions, the 372-base-pair repeat unit appears to be (A + T)-rich and noncoding and shows strong sequence conservation among units from different chromosomal regions. The nature and distribution of this sequence are suggestive of the hypothetical X chromosome DNA sequences thought to be involved in the primary establishment of sex determination and dosage compensation in Drosophila. PMID- 3106979 TI - Human epidermal Langerhans cells cointernalize by receptor-mediated endocytosis "nonclassical" major histocompatibility complex class I molecules (T6 antigens) and class II molecules (HLA-DR antigens). AB - HLA-DR and T6 surface antigens are expressed only by Langerhans cells and indeterminate cells in normal human epidermis. We have previously demonstrated that T6 antigens are internalized in Langerhans cells and indeterminate cells by receptor-mediated endocytosis. This process is induced by the binding of BL6, a monoclonal antibody directed against T6 antigens. In the present study, using a monoclonal antibody directed against HLA-DR antigens, on human epidermal cells in suspension, we show that the surface HLA-DR antigens are also internalized by receptor-mediated endocytosis in Langerhans and indeterminate cells. Moreover, using immunogold double labeling, we demonstrate that T6 and HLA-DR antigens are internalized through common coated regions of the membrane of Langerhans or indeterminate cells. The receptor-mediated endocytosis that is induced involves coated pits and vesicles, receptosomes, lysosomes, and also, in Langerhans cells, the Birbeck granules. Thus, T6 antigens, which are considered to be "unusual" or "nonclassical" major histocompatibility complex class I molecules, and the major histocompatibility complex class II molecules, HLA-DR, are internalized in Langerhans and indeterminate cells through common receptor-mediated endocytosis organelles. PMID- 3106980 TI - High-frequency expression of a conserved kappa light-chain variable-region gene in chronic lymphocytic leukemia. AB - Malignant B lymphocytes from several patients with chronic lymphocytic leukemia (CLL) were examined for reactivity with murine monoclonal antibody 17.109. This antibody, prepared against the rheumatoid factor (RF) paraprotein Sie, recognizes a crossreactive idiotype on 48% of human IgM RF paraproteins, but does not react with IgM paraproteins without RF activity or substantially with normal pooled immunoglobulin. The 17.109-reactive idiotype is a marker for a kappa III variable region gene, designated V kappa RF, that is conserved in outbred human populations. In a limited study of 31 CLL patients, the leukemic cells from 5 of 20 patients with kappa light chain-expressing CLL were recognized by the 17.109 monoclonal antibody. Despite having malignant cells specifically reactive with this antibody, patients with 17.109-positive CLL did not have elevated serum levels of circulating antibody bearing 17.109-reactive determinants. Total RNAs isolated from the CLL B lymphocytes, or from hybridomas produced by fusing the CLL cells with the WI-L2-729-HF2 cell line, were fractionated electrophoretically and examined by blot hybridization. Under stringent hybridization conditions capable of discerning a single base-pair mismatch, RNA from the 17.109-idiotype positive CLL cells hybridized to synthetic oligonucleotide probes corresponding to framework and complementary-determining regions in the V kappa RF gene. The high frequency of the 17.109-associated idiotype and the V kappa RF gene in CLL suggests that the disease may arise from B lymphocytes that express a restricted set of inherited immunoglobulin variable-region genes with little or no somatic mutation. PMID- 3106981 TI - Somatic diversification of S107 from an antiphosphocholine to an anti-DNA autoantibody is due to a single base change in its heavy chain variable region. AB - The S107 myeloma cell line expresses the germ-line sequence of the T15 antiphosphocholine (P-Cho) antibody, which is the major antibody made by BALB/c mice in response to P-Cho, either on a variety of bacterial polysaccharides or when attached to a protein carrier. We have previously reported that a somatic mutant of the S107 cell line produces an antibody that has lost the ability to bind P-Cho and has acquired binding for double-stranded DNA. This antibody has a substitution of an alanine for a glutamic acid at residue 35 in the heavy chain variable region. We now show that this amino acid substitution is due to a single A-C transversion, which is the only nucleotide change in the heavy and light chain variable regions. Further, it appears that this change is due to somatic mutation rather than to gene conversion. PMID- 3106982 TI - Antiviral activity of mismatched double-stranded RNA against human immunodeficiency virus in vitro. AB - The biological response modifier r(I)n.r(C12-U)n, referred to here as mismatched double-stranded (ds) RNA, was examined for antihuman immunodeficiency virus (HIV) activity in vitro because of its known antiviral activity and ability to induce interferon (IFN) in other biological systems [Carter, W. A., Strayer, D. R., Hubbell, H. R. & Brodsky, I. (1985) J. Biol. Response Modif. 4, 495-502]. We found that cultures of the highly HIV-permissive T-cell line C3 were afforded significant protection from HIV infection when incubated in growth media supplemented with mismatched dsRNA at 10-50 micrograms/ml prior to virus challenge. Similar results were obtained at 50 micrograms of mismatched dsRNA per ml in cultures of the T-lymphoblastoid cell line CEM. Infections were monitored by indirect immunofluorescence of cells for viral p24 antigen expression, reverse transcriptase activity in culture fluids for virus production, and vital dye uptake for cytopathic effect. Antiviral activity was increased by the continued presence of mismatched dsRNA in cultures following virus challenge. A one-time exposure to mismatched dsRNA (50 micrograms/ml) provided greater antiviral activity than either a one-time exposure to recombinant IFN-alpha [250 international units (IU)/ml], IFN-beta (250 IU/ml), or IFN-gamma (50 IU/ml) in cultures of CEM cells, or a one-time exposure to a combination of all three IFNs (150 IU each per ml) in cultures of C3 cells. Mismatched dsRNA at 50 micrograms/ml had no effect on cell division, RNA and protein synthesis, or virus replication in all T-cell lines examined. A clear distinction between the activities of mismatched dsRNA and IFN was the ability of IFN to suppress the in vitro replication of HIV that occurred at IFN concentrations (150 IU each of alpha, beta, and gamma per ml) that provided less antiviral activity than mismatched dsRNA (50 micrograms/ml). The results of these in vitro studies suggest a potential therapeutic value for mismatched dsRNA in the treatment of acquired immunodeficiency syndrome (AIDS). PMID- 3106983 TI - Nonrandom allele associations between unlinked protein loci: are the polymorphisms of the immunoglobulin constant regions adaptive? AB - Consistent linkage disequilibrium was observed between independently segregating protein loci. In natural populations of the European rabbit Oryctolagus cuniculus, highly significant, nonrandom associations between alleles of the constant regions of the immunoglobulin light and heavy chains were found, both within localities and between localities. We suggest that the population genetic data presented here are relevant to the adaptive significance of the genetic polymorphisms of the antibody constant regions. PMID- 3106984 TI - Role of intracellular calcium in renal nerve-mediated renin release. AB - We evaluated the role of intracellular calcium in renal nerve-mediated renin release in four groups of anesthetized dogs. Each dog received renal nerve stimulation (RNS)(0.5 Hz) twice as follow: control, RNS, recovery; control, RNS, recovery. Group 1 served as time control. Group 2 received Ca ionophore A23187 (Io) and Groups 3 and 4 received verapamil at 2.5 and 5 micrograms/kg X min respectively during the second RNS. In Group 1, renin secretion rate (RSR) increased from 95 +/- 22 to 223 +/- 73 (P less than 0.05) and from 13 +/- 5 to 108 +/- 20 ngANG I/hr X min (P less than 0.005) during the first and second RNS, respectively. In Group 2, RSR increased from 210 +/- 85 to 402 +/- 118 (P less than 0.02) and from 88 +/- 11 to 157 +/- 39 ngANG I/hr X min (NS) during the first and second RNS, respectively. In both groups, systemic and renal hemodynamics and UNaV did not change. In Group 3, verapamil alone did not increase RSR. During RNS, RSR also did not increase. In Group 4, verapamil alone increased RSR from 42 +/- 12 to 273 +/- 71 ngANG I/hr X min (P less than 0.03) despite a similar reduction in systemic blood pressure as in Group 3. RNS did not increase RSR further during verapamil infusion. The present study suggests that increased intracellular Ca by Io inhibits renal nerve-mediated renin release. A low dose of verapamil has no effect on renin release and does not augment renal nerve-mediated renin release. A high dose of verapamil increases renin release but does not enhance RNS-mediated renin release. We conclude that intracellular calcium plays an important role in renin release and may be the final messenger in renal nerve-mediated renin release. PMID- 3106985 TI - Effects of cycloheximide during the periovulatory period on ovarian follicular FSH, hCG, and prolactin receptors and on follicular maturation in the hamster. AB - Hamsters were injected sc at 1400 hr on proestrus with either 4 mg cycloheximide (which blocks ovulation but only transiently affects ovarian protein synthesis) or saline and killed at 2-hr intervals until 0400 hr on estrus. After cycloheximide, the first surge of FSH (at 1600 hr) was half the normal value and the second surge of FSH (beginning at 2200 hr) was eliminated. Control follicles at 1400 hr had approximately the same number of FSH and hCG receptors with about one-third as many PRL receptors. Down regulation of FSH and hCG receptors for control follicles occurred by 2400 hr while PRL receptors dropped abruptly 4 hr earlier. Compared to the 1400-hr control values, the maximal loss of FSH, LH, and PRL receptors was 40, 45, and 85%, respectively. Although cycloheximide tended to slightly delay the loss of FSH receptors at 2000-2200 hr it did not prevent the ultimate fall in FSH and hCG receptors; the loss of PRL receptors was accelerated by 4 hr. Cycloheximide prevented or delayed follicular growth, resumption of meiosis, and cumulus expansion. The altered proestrous profile of steroids after cycloheximide (prolonged follicular estradiol and reduced progesterone) is therefore not associated with drastic alterations in the number of FSH and hCG binding sites. On the other hand, PRL receptors represent fast turnover protein(s). PMID- 3106986 TI - Possible involvement of the phospholipases in the mitogenic actions of prolactin (PRL) on Nb2 node lymphoma cells. AB - The possible role of the phospholipase enzymes in the prolactin stimulation of mitogenesis in Nb2 node lymphoma cells was investigated. Two phospholipase inhibitors including quinacrine and alpha-para-dibromoacetophenone (BPB) were employed. Quinacrine at concentrations of 1-5 microM attenuated the magnitude of the PRL stimulation of cell division; at concentrations of 10 microM and above quinacrine abolished the PRL response. BPB at concentrations of 1-10 microM also inhibited the mitogenic effect of PRL in a concentration response fashion. The polyunsaturated fatty acid arachidonic acid partially reversed the inhibitory effects of these drugs. In further studies, exogenously added phospholipase C at concentrations of 5-50 ng/ml was found to potentiate the mitogenic effect of prolactin when prolactin was employed at a concentration that evoked a half maximal response. By itself, however, phospholipase C had no effect on the rate of cell division. Phospholipase A2 either by itself or in the presence of prolactin was without effect. PMID- 3106987 TI - Endothelium-dependent vasorelaxation induced by Cn-acetal plasmalogens. AB - In this study the effects of the synthetic acetal plasmalogens (AP) C17-AP, C13 AP, C9-AP on isolated rabbit aorta were investigated with emphasis on their putative relationship with endothelium-dependent relaxing factor (EDRF). The various AP were obtained by total synthesis from the related fatty acid chlorides. In isolated rabbit aorta precontracted with phenylephrine (PE, 10(-7) M), C17-AP (greater than 10(-6) M) and C13-AP (greater than 10(-5) M) exerted an endothelium-dependent relaxation (EDR). In contrast, C9-AP was totally devoid of effect. Given 30 or 45 min before PE, C17-AP (greater than 10(-6) M) and C13-AP (greater than 10(-5) M) abolished the carbachol-induced ERD; moreover, following preincubation with C17-AP, enhanced contraction was obtained with carbachol. Similar effects were obtained with preincubation of aortas with both AA(10(-4) M) and A 23 187 (10(-8) M). Conversely preincubation of aortas with carbachol (3X 10(-6) M) and ATP (3 X 10(-5) M) did not significantly modify the carbachol induced EDR. Atropine (3 X 10(-7) M) did not affect the relaxation induced by C17 AP and C13-AP. The in vivo effects are correlated with the in vitro actions of acetal plasmalogens: C17-AP and C13-AP but not C9-AP, given iv (5 mg/kg) induced a pronounced but transient hypotension which lasted 2-3 min and which was followed by a persistent hypertensive state. Atropine (0.5 and 1 mg/kg; iv) given 5 min before C17-AP inhibited the secondary hypertensive phase. These results show that C17-AP and C13-AP should be added to the list of compounds capable of releasing EDRF. PMID- 3106989 TI - Conversion of arachidonate to prostanoids by lung microsomes from rats fed varying amounts of vitamin E. AB - This study was conducted to investigate the effect of dietary vitamin E on prostaglandin (PG) synthesizing activities in the rat lung. Five groups of weanling male rats were fed for 9 wk a vitamin E deficient diet supplemented with 0, 20, 40, 200 and 400 mg-dl-alpha-tocopherol acetate/kg (E0, E20, E40, E200 and E400). Microsomes from lungs of each group were incubated in the presence of [1 14C]-arachidonate. Separation of metabolites was achieved by reversed phase HPLC. Six prostanoids: 6-keto-PGF1 alpha, 6-keto-PGE1, TXB2, PGF2 alpha, PGE2 and PGD2 were eluted isocratically with the solvent system of acetonitrile-water (pH 3.0) (34:66, V/V). Fractions of eluent were collected and the radioactivity of each fraction was determined. The predominant prostanoid synthesized by rat lung microsomes was 6-keto-PGF1 alpha. The specific activity (pmole PG produced/mg protein/min) for the synthesis of 6-keto-PGF1 alpha was 17.6, 29.3, 16.3, 15.3 and 21.2 for the E0, E20, E40, E200 and E400 groups, respectively. Only minor amounts of 6-keto-PGE1, TXB2, PGF2 alpha, PGE2 and PGD2 were synthesized by rat lung microsomes. Although rats fed vitamin E at 20 mg/kg diet showed the highest enzymatic activity for the synthesis of 6-keto-PGF1 alpha, dietary vitamin E had little overall effect on lung microsomal prostanoid biosynthesis. PMID- 3106988 TI - Differential effects of putative inhibitors on cytosolic and membrane associated platelet lipoxygenase. AB - The effects of Indomethacin, Esculetin, ETYA (4, 7, 10, 13-eicosatetraynoic acid, U53119), 3-amino-1-trifluoromethyl-7-phenyl-pyrazoline (BW 755C), Quercetin, Phenidone, and Nordihydroguaretic acid (NDGA) on the synthesis of 12-L hydroxyeicosatetraenoic acid (12-HETE) by human platelet 12-lipoxygenases were investigated. Except Indomethacin and Esculetin, all other drugs demonstrated significant inhibitory effect on 12-lipoxygenase activity. The rank order of potency for the inhibition of lipoxygenase in intact human platelets was ETYA greater than Quercetin greater than NDGA greater than Esculetin greater than Indomethacin. BW755C and Indomethacin were effective against platelet cyclooxygenase also. ETYA (U53119) was the most potent and selective inhibitor of platelet lipoxygenases. Results of our studies suggest that known lipoxygenase inhibitors display differential effects on platelet cyclooxygenase as well as membrane and cytosol associated lipoxygenases. PMID- 3106990 TI - Effect of the 5HT2 antagonist ritanserin on food intake and on 5HT-induced anorexia in the rat. AB - The present study investigated the effect on the rat's eating behavior of the new selective 5HT2 antagonist ritanserin. The results obtained indicate that: single subcutaneous (SC) injection of ritanserin, at doses between 0.1 and 1 mg/kg b.wt., neither elicits food intake in sated rats, nor increases the intake induced by food deprivation; subchronic SC treatment (15 days) with 0.1 mg/kg does not increase food intake nor body weight gain; subchronic SC treatment with high doses, 1 or 10 mg/kg, produces small and transient increases in food intake without affecting body weight gain. When ritanserin was tested for its ability to block the anorectic effect of exogenous 5HT, it inhibited the effect of intraperitoneal (IP) 5HT, but proved to be completely inactive versus the effect of 5HT injected into the hypothalamic paraventricular nucleus, which is highly sensitive to this effect of 5HT. This last finding suggests that the anorectic action of central endogenous 5HT is also not blocked by ritanserin, thus proposing a reasonable explanation for the absence of orexigenic effect following its administration. Moreover, it suggests that in rats the hypothalamic receptors mediating the effect of 5HT on eating behavior are different from the 5HT2 of the frontal cortex which have been shown to be completely blocked by ritanserin under the experimental conditions employed in our study. PMID- 3106991 TI - Studies on the central action of L-threo-3,4-dihydroxyphenyl-serine (L-threo DOPS) in FLA-63-treated mice. AB - In order to clarify the central action of L-threo-DOPS, the effect of benserazide on behavioral and biochemical changes by L-threo-DOPS in FLA-63-treated mice was studied. L-threo-DOPS in combination with nialamide markedly increased both the locomotor activity and the concentrations of the brain, heart and kidney norepinephrine (NE) in the FLA-63-treated mice. Benserazide at low doses did not alter either the rise of the brain NE level or the increase in locomotor activity, whereas it significantly inhibited the rise of the heart and kidney NE levels. Benserazide at a high dose significantly inhibited all of them. These results suggested that the increase in locomotor activity might be mediated via activation of the central noradrenergic neurons system by L-threo-DOPS. PMID- 3106992 TI - Reduced anti-immobility effect of repeated desipramine (DMI) treatment in adult rats undernourished at perinatal age. AB - Adult rats submitted to a protein deprivation schedule at perinatal age showed a reduced anti-immobility effect following seven days of DMI treatment (20 mg/kg/day) in the forced swimming test. The ineffectiveness of DMI treatment is attributed to the inability of deprived animals to produce neuronal adaptative changes in central monoaminergic pathways. PMID- 3106993 TI - The pyrazoloquinoline, CGS 8216, reduces sham feeding in the rat. AB - The pyrazoloquinoline CGS 8216, a benzodiazepine receptor ligand, produced a dose related (2.5-10.0 mg/kg, IP) attenuation of sham feeding a 30% sucrose solution by rats with open gastric fistulas. Ingestion was reduced by over 50% following the largest dose of CGS 8216 in a 60 min test. The initiation of sham feeding was not delayed by CGS 8216, but sham feeding was subsequently slowed over an extended test period. The suppressant effect of CGS 8216 was reversed by the specific benzodiazepine receptor antagonist Ro15-1788 (20 and 40 mg/kg, IP). Hence the effect of CGS 8216 on sham feeding may be mediated by benzodiazepine receptors, and is consistent therefore with the characterization of CGS 8216 as a benzodiazepine partial inverse agonist. In contrast to sham feeding, CGS 8216 (10.0 mg/kg, IP) did not affect sham drinking in 17 hr water-deprived rats. The results are discussed in relation to possible benzodiazepine receptor involvement in the neurochemical mediation of food palatability. PMID- 3106994 TI - Influence of polyethylene glycol 6000 and mannitol on the in-vitro dissolution properties of nitrofurantoin by the dispersion technique. AB - Employing the dispersion technique the influence of mannitol and polyethylene glycol (PEG) 6000 on the in-vitro dissolution of nitrofurantoin was investigated. Dispersions of the drug with PEG 6000 showed faster dissolution rates when compared with dispersions of the drug in mannitol. Tablet formulation of the drug -PEG 6000 dispersion exhibited better drug releasing properties as compared to tablets prepared from the drug's PEG 6000 physical mixture, or the drug's formulation with Avicel PH 101. PMID- 3106995 TI - Determination of three parameters describing the uncollimated electron beam in air. AB - The parameters that describe the electron dose distribution phi (r, theta, z) produced in air by an uncollimated clinical electron beam are accurately determined. For the determination of these parameters the multiple scattering theory of Fermi is assumed. A new method which determines the angular variance at the phantom surface is introduced and the results appear to be in good agreement with the multiple scattering theory. Knowledge of the values of these parameters is essential for a numerical determination of the dose distribution in air and in the patient. PMID- 3106996 TI - Description of the uncollimated electron beam in air by means of a directional pencil beam model. AB - The dose distribution of an uncollimated electron beam in air, described by phi(theta x, x, z), is shown to be mathematically equivalent to a directional pencil beam model. In this model the multiple scattering theory of Fermi is assumed. After implementation of the model by using a computer program, dose distributions of electron fields of various shapes were calculated and compared with dose distributions obtained by experiment. In general, the distributions appear to agree well, but in some situations noticeable differences can be observed, which is probably due to the fact that large-angle scattered electrons are not considered in this model. PMID- 3106997 TI - Gold thioglucose-induced brain lesions in hamsters. AB - Previous studies suggest species differences in the central neural effects of gold thioglucose (GTG). To further assess these differences, we studied the effects of single intraperitoneal injections of GTG on the brains of golden hamsters (Mesocricetus auratus). Within 48 hr of treatment, each of the GTG doses tested (500, 1000 and 1500 mg/kg) had produced lesions in the ventromedial hypothalamus and area postrema. These findings are of interest since they identify the hamster as the first animal known to be susceptible to GTG-induced lesion formation, but resistant to the hyperphagia commonly associated with glucose analog glucoprivation. PMID- 3106998 TI - Influence of regimen and insulinemia on orexigenic effects of GRF1-44 in sheep. AB - The effects of intracerebroventricular (ICV) and intravenous (IV) administration of human GRF1-44 on feeding behavior were tested in hay- and concentrate-fed non lactating ewes. Administered ICV 5 min prior to hay disposal in 16 hr fasted ewes, GRF1-44 increased the first 3 hr and daily (8 hr) food intake by 25.3 and 24.5% respectively; this corresponded to a higher rate of ingestion during the first 3 hr. Similar effects on feeding behavior were observed after IV administration of a 10-times greater dose of GRF1-44 (1 microgram X kg-1), with daily hay consumption increasing from 1125 +/- 44 g (control) to 1407 +/- 91 g. In contrast, food intake of concentrates was significantly (p less than 0.05) higher only during the first hour of feeding and the daily food intake was unchanged. Both ICV (40 mU X kg-1) and IV (400 mU X kg-1) administrations of insulin did not affect feeding behavior per se, but suppressed the increased food intake of hay induced by IV GRF1-44. It is concluded that the orexigenic effects of GRF1-44 are probably centrally mediated and depend on regimen and digestive status. It is suggested that the insulin response to a meal of concentrates may be responsible for the early blockade of the orexigenic effects of GRF. PMID- 3106999 TI - Water drinking caused by intracerebroventricular infusions of hypertonic solutions in cattle. AB - Infusions into the lateral cerebral ventricle of hypertonic solutions of NaCl, mannitol or sucrose all induced water drinking in cattle. However, infusion of hypertonic NaCl caused a significantly greater water drinking response than did the infusions of mannitol or sucrose, despite the fact that CSF osmolality increase was similar. In contrast, hypertonic solutions of NaCl or mannitol had similar dipsogenic effects when infused intravenously. The intracerebroventricular infusions of hypertonic NaCl or mannitol did not affect the intakes of food or Na solution. The results are consistent with the hypothesis that both cerebral osmoreceptors and Na sensors are involved in regulating thirst in cows. PMID- 3107000 TI - Changes in sodium appetite in cattle induced by changes in CSF sodium concentration and osmolality. AB - Alteration of the sodium concentration in the cerebrospinal fluid (CSF) of sheep induces reciprocal changes in sodium appetite. Similar studies have now been performed in cattle. Heifers were prepared with a unilateral parotid fistula and guide tubes were implanted in the skull for the introduction of probes into the lateral ventricles in order to sample CSF and infuse artificial CSF solutions. The cows were Na depleted by loss of saliva for 46 hr and then given free access for 2 hr to 300 mM NaCl/NaHCO3 solution. Artificial CSF infusions at 1.9 ml/hr were begun one hour before Na access. In control experiments, the cows drank 26.4 +/- 1.2 l of Na solution in 2 hr, 1.2 +/- 0.2 l of water in the preceding hour, and 0.3 +/- 0.1 l of water during Na access. Sham or standard isotonic CSF infusions did not alter these values. CSF [Na+] rose from approximately 142 to approximately 148 mmol/l, attributable to the effects of drinking the large volume of hypertonic Na solution. Infusion of 500 mM NaCl CSF increased CSF [Na+] and reduced Na intake and increased water intake. Infusion of 700 mM mannitol: 150 mM NaCl CSF reduced CSF [Na+] and increased both Na and water intake. Infusion of a mixture of these solutions had no effect on CSF [Na+] and increased water intake only. Infusion of 270 mM mannitol CSF reduced CSF [Na+] and slightly reduced Na intake. Standard isotonic CSF containing 0.5 or 2.0 micrograms/ml of angiotensin II increased water intake only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107001 TI - Separate mechanisms for central osmotically-induced drinking and vasopressin release in minipigs. AB - Operant drinking and lysine vasopressin (LVP) release were investigated in minipigs following intracerebroventricular (ICV) injections of hypertonic equiosmolar (1.4 osM) solutions of NaCl and of sucrose and mannitol dissolved in 0.15 M NaCl or water, and of urea dissolved in 0.15 M NaCl. Hypertonic (0.74 M) NaCl produced significant drinking and LVP release in all minipigs tested whereas hypertonic equiosmolar (1.4 osM) solutions of sucrose and mannitol induced only drinking. Mannitol, both with and without NaCl, was more effective than sucrose. Hypertonic urea was ineffective both as an osmotic dipsogen and at stimulating the release of LVP. These results suggest that two independent mechanisms could be involved in drinking and LVP responses to ICV administration of hypertonic solutions in minipigs. PMID- 3107002 TI - Characterization of self-transmissible plasmids determining lactose fermentation and multiple antibiotic resistance in clinical strains of Klebsiella pneumoniae. AB - The lactose fermentation (Lac+) and antibiotic resistance (R+) phenotypes were conjugally transferred from Klebsiella pneumoniae strains (K166, K182, K186, K218, and K220) to Salmonella typhi, S. typhimurium, Shigella flexneri, and Vibrio cholerae. The genes for lactose fermentation and antibiotic resistance were located on the plasmids. Further analysis of plasmid DNA from these isolates indicated the presence of multiple plasmids (Mr ranged less than 2.7 to 70 X 10(6)). The Lac+R+ plasmids p166 and p182 were members of the FII incompatibility group. The fertility inhibition property of plasmids, p182, p218, and p220 was fi+ type. Furthermore, phage typing experiments showed that plasmids p166 and p218 (Lac+R+) conferred the ability to inhibit the multiplication of bacteriophages 12 and 13 in S. typhimurium. However, the plasmids p182, p186, and p220 (Lac+R+) could inhibit the visible lysis of all the 30 phages in S. typhimurium. This study describes the characterization of Lac+R+ plasmids and the medical significance of an intergeneric transfer of lactose fermentation to non lactose-fermenting pathogens. PMID- 3107003 TI - Chloramphenicol resistance cloning vector based on pUC9. AB - Plasmid pPR328 has been constructed for use as a chloramphenicol-resistant, intermediate cloning vector when manipulating DNA fragments cloned in vectors of the pUC family. The method used in its construction may be of general use for the replacement of the ampicillin resistance marker of pBR322-based plasmids with other drug resistance cassettes. PMID- 3107004 TI - Streptococcus faecalis sex pheromone (cAD1) response: evidence that the peptide inhibitor excreted by pAD1-containing cells may be plasmid determined. AB - Streptococcus faecalis strains harboring the conjugative plasmid pAD1 excrete a small peptide, iAD1, which inhibits the sex pheromone cAD1. Studies making use of the host strain Streptococcus faecium 9790, which normally does not excrete peptide pheromones, suggest that iAD1 may be determined directly by pAD1. PMID- 3107005 TI - [Learning ability in adulthood. A contribution to clinical developmental psychology]. PMID- 3107006 TI - [Specific aspects of psychological disorders of performance in children with epilepsy]. AB - We examined 49 normal intelligent epileptic and parallelised in sex, age and intelligence just as much healthy and 14 minimal cerebral damaged children without seizures. Using a psychological test battery psychic/psychomotor speed, flexibility/preservation proneness, memory span and memory and concentration were registrated. Besides reduced memory performances we found a deceleration of psychic/psychomotor speed as primary basic disorder within the performance structure of epileptic children analogous to our previous examined adults. The tridimensional comparison suggests remarkable psychopathological differences among the two groups of patients. PMID- 3107007 TI - [Fitness for automobile driving of patients at an epilepsy outpatient care unit]. AB - Patients who were free from seizures and not in possession of a driving license were examined for reasons for their being considered unfit to drive at an outpatient care centre for epileptics catering for 477 patients. The composition of the group was analyzed in respect of age, sex, intake of pharmaceuticals, risk factors and appropriateness of behaviour in traffic. Corresponding conclusions are drawn. PMID- 3107009 TI - CO2 vulnerability in panic disorder. AB - The immediate effects of a single inhalation of a 35% CO2 mixture in oxygen were examined in 12 patients with panic disorders and 11 normal control subjects. Compared to a placebo air inhalation, the CO2 inhalation provoked short-lived autonomic panic symptoms in both patients and normals; it also elicited high subjective anxiety in patients with panic disorders. The latter rated the overall CO2-induced state as very similar to a real-life panic attack. PMID- 3107008 TI - [Long-term patients at the acute psychiatric hospital--a status determination and catamnestic study]. AB - 119 so-called "long-term" hospitalised patients (more than 4 months stay in the hospital) have been described by the records of illness and the AMDP documentation system. They were also examined 1 year after discharge. 92.5% of the "long-term" patients have been classified as "improved" or "well improved" when leaving the hospital. 1 year later 51.6% of those patients showed the same psychopathological state, 14.3% showed a better state and 28.6% had decreased. 5 patients had committed suicide. The family situation had improved only for 10% of the patients and 8.1% showed a decrease. The professional level of 20.9% decreased. Only 8.2% where able to improve themselves. The "typical long-term patient" suffers from a schizoaffective or affective psychosis. He is either between 18 and 29 or older then 60 years. He is unmarried, and has never or only few times been in hospital before. He leaves the hospital after long stay as "improved" or "well improved". One year later this success by a long-term indoor treatment proved still to be stabile with 2/3 of the patients. The results are compared with those in literature and the problem of "long-term" hospitalisation is discussed. PMID- 3107010 TI - Male gender identity: early developmental roots. AB - The purpose of this paper has been to bring together a wide variety of ideas about male gender and sexual development into a broader and updated view. Toward that end, I have suggested that we view the concept of gender identity along three intertwining strands; core gender identity, gender role identity, and choice of love object. I have also suggested some important contributions made to each of these strands at various phases of development. I have concentrated upon the early childhood roots of gender identity, particularly as the earliest years are the time when important internal structures are established and consolidated. Later manifestations, although not the same as the early ones, have their roots in the early childhood configurations. However, the contributions to an overall broad sense of gender identity made during the latency and adolescent years must not be overlooked. The final outcome of any position along any of the strands is not finally consolidated until the end of adolescence. Indeed, adult experiences may also make important contributions. PMID- 3107011 TI - Toward a new psychology of men: psychoanalytic and social perspectives. PMID- 3107012 TI - The male superego. PMID- 3107013 TI - Becoming a father: a psychoanalytic perspective on the forgotten parent. AB - This article has presented a psychoanalytic perspective on the process of becoming a father. It began with a discussion of the neglect of the father during pregnancy and briefly considered evidence as to the unique contributions made by fathers of the newborn. Nine psychodynamically based wishes emerging throughout the developmental process were next proposed to embody the male's motivation to become a father. The final section examined seven specific phases of expectant fatherhood, from getting ready through parturition. PMID- 3107014 TI - Fathering from infancy to old age: a selective overview of recent psychoanalytic contributions. PMID- 3107015 TI - The psychoanalytic model of male homosexuality: a historical and theoretical critique. PMID- 3107016 TI - Turning women things into men: masculinization in Papua New Guinea. PMID- 3107017 TI - Oedipus and the aging male: a comparative perspective. PMID- 3107018 TI - The myth of the death of the hero: a Jungian view of masculine psychology. PMID- 3107019 TI - Fantasies of college men: then and now. PMID- 3107020 TI - Concerning a psychoanalytic view of maleness. PMID- 3107021 TI - Male-female relationships: 600 years of change. PMID- 3107022 TI - Divorce, oedipal asymmetries, and the marital age gap. PMID- 3107023 TI - College youth: gender roles in flux. PMID- 3107025 TI - "For better and for worse". PMID- 3107024 TI - Some observations regarding men's contemporary views on women. PMID- 3107026 TI - Psychopharmacology of midalcipran, 1-phenyl-1-diethyl-amino-carbonyl-2 aminomethylcyclopropane hydrochloride (F 2207), a new potential antidepressant. AB - Midalcipran is a new potential antidepressant selected for its equipotent inhibition of noradrenaline and serotonin uptake and its lack of effect at any postsynaptic receptor. In mice it antagonized the depressant effect of tetrabenazine with an oral ED50 value of 0.5 mg/kg as compared to 2.5 mg/kg for desipramine and 5.1 mg/kg for imipramine. Similar findings were obtained for the inhibition of yohimbine-induced mortality. In the "behavioral despair" test, in mice, immobility was significantly reduced by 10 mg/kg midalcipran whereas 20 mg/kg of desipramine was required for a similar effect. Midalcipran enhanced the behavioral changes induced by 1-tryptophan in the rat and antagonized p chloramphetamine-induced hyperthermia in mice. In contrast to tricyclic antidepressants, midalcipran showed no anticholinergic, sedative or stimulant properties. PMID- 3107027 TI - Drug deprivation and reinforcement by diazepam in a dependent population. AB - Individuals who were using therapeutic doses (approximately 15 mg diazepam or its equivalent daily) of a benzodiazepine persistently and wished to attempt to stop were recruited into a study offering a medically supported outpatient behavioral treatment with a goal of abstinence. All subjects received the same behavioral treatment that emphasized the development of strategies for coping with abstinence and alternatives to benzodiazepines as a coping mechanism. The goal of abstinence was to be achieved within approximately 8 weeks by means of gradual tapering of the daily dose. Some subjects (Group D, n = 23) were randomly assigned to a condition in which their dose was to be tapered on a regime of active diazepam. Others (Group P, n = 19) were switched to placebo at the first treatment session and "tapered" from this pharmacologically inert substitute for diazepam. Supplies of tablets of each preparation were provided by the experimenters, and subjects were specifically requested to use only those tablets. The principal dependent variable was "supplementation", or use of a benzodiazepine other than that specifically authorized by the therapist. Supplementation was detected by measures of plasma benzodiazepine levels as compared to levels predicted if there had been strict compliance with the therapeutic regime. These comparisons were made by two expert judges who were blind to the subjects' experimental assignment. Self-report of supplementation was also obtained. Plasma level determinations indicated a significantly greater frequency of supplementation (84% versus 33% of subjects) for subjects in Group P.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107028 TI - BM-5, a centrally active partial muscarinic agonist with low tremorogenic activity. In vivo and in vitro studies. AB - The acute and chronic effects of the centrally active oxotremorine analog, BM-5, [N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)-acetamide] were examined in rats and mice. In vivo studies in mice and rats indicated that this compound is a partial muscarinic agonist with large regional differences in its efficacy: BM-5 produced low tremor in doses which evoke full salivary response. The maximal tremor response to BM-5 was much smaller than that produced by oxotremorine, while the maximal salivary response to BM-5 was greater than that evoked by oxotremorine. The tremor response to BM-5 was bell-shaped, the peak dose being around 2 mg/kg. In contrast, the salivary response increased with increasing doses of BM-5. The apparent muscarinic antagonist properties of higher doses of BM-5 were specific to the striatum in which BM-5 (0.05-10 mg/kg) caused significant decreases in the level of acetylcholine while these levels were unaltered in the cerebral cortex, hippocampus, and brainstem. Pretreatment of rats with BM-5 (5 mg/kg) also prevented the increase in striatal acetylcholine induced by oxotremorine (0.75 mg/kg). Chronic treatment of mice with BM-5 (0.2-2 mg/kg) for 14 days also showed that BM-5 at higher doses, behaved as an antagonist, since it caused supersensitivity to oxotremorine on the tremor response. In addition, the number of receptor sites, as measured by binding of 3H 3-quinuclidinyl benzilate (3H-3-QNB), was increased in the striatum while no similar increase was observed in other brain areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107029 TI - The effect of kappa-opioid agonist U-50, 488H on wet-dog shaking behavior induced by hippocampal stimulation in rats. AB - The effect of a selective kappa-opioid agonist, U-50, 488H, on wet-dog shaking (WDS) induced by hippocampal stimulation was investigated and compared with that produced by morphine. U-50, 488H, as well as morphine, inhibited the appearance of WDS in a dose-dependent manner. U-50, 488H was approximately three times more potent than morphine in this effect. Neither drug showed any effect on hippocampal afterdischarge. The inhibition of WDS produced by U-50, 488H was blocked significantly by a kappa-opioid antagonist, MR-2266, but not by naloxone. On the other hand, the inhibitory effect of morphine was completely antagonized by both MR-2266 and naloxone. The present results strongly suggest that not only mu-but also kappa-opioid receptors are involved in the appearance of WDS induced by hippocampal stimulation. PMID- 3107030 TI - Effects of fluprazine (DU27716) and ethanol on target biting behavior and intruder-evoked attacks. AB - The effects of an "aggression"-reducing drug, fluprazine, and an "aggression" enhancing drug, ethanol, were evaluated in mice using the target biting and resident-intruder paradigms. Under baseline conditions there was a high target biting rate immediately after the delivery of a 2.0 mA tail shock, an intermediate target biting rate during a 2-min intershock interval, and a low target biting rate during a 15-s tone stimulus which signaled the shock. During the 10-min resident intruder test sessions, resident males attacked bulbectomized intruders an average of 11.3 times with an average latency to the first attack of 68.3 s. Fluprazine caused a dose-dependent decrease in postshock and intershock interval target biting behavior, increased the latency to the first attack, and decreased the number of attacks in the intruder-evoked aggression paradigm. Ethanol exerted a biphasic effect in both paradigms. A dose of 0.5 g/kg increased and 4.0 g/kg decreased intershock interval target biting behavior. Likewise, ethanol at a dose of 1.0 g/kg increased the number of intruder-evoked attacks and 0.5 g/kg reduced the latency to the first attack whereas 2.0 g/kg ethanol reduced the number of intruder-evoked attacks. These observations are discussed in reference to the specificity with which different drugs and paradigms are able to dissociate offensive versus defensive aggression. PMID- 3107032 TI - Reduction in 2-deoxy-D-glucose analgesia following acute, but not chronic antidepressant treatment. AB - Acute, but not chronic, antidepressant treatment potentiates the analgesic responses following cold-water swims. The present study evaluated the effects of acute (10 mg/kg) and chronic (10 mg/kg, twice daily over 7 days) pretreatment with desipramine (DMI) upon the analgesic response following 2-deoxy-D-glucose (2DG) in rats as measured by the jump test. Acute, but not chronic, DMI pretreatment significantly reduced 2DG analgesia. These effects are discussed in terms of the heterogeneity of pain-inhibitory responses. PMID- 3107033 TI - Conditioned taste aversion induced in rats by intracerebral or systemic administration of monoamine oxidase inhibitors. AB - Conditioned taste aversion (CTA) elicited by systemic or intracerebral application of the monoamine oxidase inhibitors clorgyline (C), pargyline (P) or deprenyl (D) was studied in 402 rats. Water-deprived animals were allowed 15 min access to 0.1% sodium saccharin (CS) followed 10 min later by IP or by intracerebral injection of the drug. In the latter case, the animals were anesthetized 5 min after saccharin drinking with pentobarbital and the drug was stereotaxically injected (1 microliter/min, 1-2 microliters) into the target structure. CTA was assessed in a two-choice retention test performed 2 days later. A geometric progression of three to six dosages applied to groups of rats (n = 10) was employed to establish the effective doses of the drugs which were 4, 20 and 32 mg/kg with IP and 2.5, 10 and 80 micrograms per rat with intracerebral (n. raphe magnus) injections of C, P, and D, respectively. The ratios of intracerebral to systemic dosages eliciting comparable CTA were 1:300 for C, 1:800 for P and 1:100 for D. Injections of 2.5 micrograms C and 10 micrograms P into the mesencephalic reticular formation, medial hypothalamus and cerebral cortex were ineffective, as were injections of 10 micrograms P into the nucleus of the solitary tract and cerebellum. The results indicate that CTA is elicited more efficiently by inhibition of monoamine oxidase A (selectively inhibited by C) than of monoamine oxidase B (selectively inhibited by D). PMID- 3107031 TI - Hyperactivity induced by dexamphetamine/chlordiazepoxide mixtures in rats and its attenuation by lithium pretreatment: a role for dopamine? AB - Dexamphetamine (DEX) and chlordiazepoxide (CDZP) given together as mixtures have previously been shown to induce a characteristic "compulsive" form of locomotor hyperactivity in rats placed in unfamiliar environments, which was much greater than activity obtained with any dose of either drug given separately; acute pretreatment with lithium counteracted mixture-induced hyperactivity. The role of dopamine in these effects was investigated by measuring concurrently the levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. DEX (0.02-2 mg kg-1) increased horizontal (entries) and vertical (rears) activity, and increased DA and decreased DOPAC and HVA in the striatum. Chlordiazepoxide (CDZP) (12.5 or 20 mg kg-1) increased horizontal activity but did not affect vertical activity or DA or its metabolites. Lithium by itself in acute (2 meq kg-1, 24 and 4 h before test) or extended (2 meq kg-1 daily for 9 days) dosage had little effect on horizontal or vertical activity or levels of DA or DOPAC. Given together, DEX and CDZP (1.18 mg kg-1 + 12.5 mg kg-1), as expected, increased entries much more than did either drug given separately, but rears and levels of DA and metabolites remained similar to those with DEX given alone. Acute lithium pretreatment counteracted the mixture-induced increase in entries. Neither acute nor extended lithium pretreatment significantly altered DEX-induced changes in activity or levels of DA or DOPAC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107034 TI - Beta-funaltrexamine antagonizes the discriminative stimulus effects of morphine but not naltrexone in pigeons. AB - Antagonistic actions of the irreversible, mu-selective antagonist beta funaltrexamine (beta-FNA) were evaluated in pigeons trained to discriminate among intramuscular injections of morphine (5.6 mg/kg), saline, and naltrexone (10.0 mg/kg). Beta-FNA administered alone (1.0 or 10.0 mg/kg) failed to mimic the discriminative stimulus effects of morphine or naltrexone. Beta-FNA attenuated the discriminative stimulus effects of morphine. A three-fold larger dose of morphine was required for complete generalization when pigeons were pretreated with a dose of 1.0 mg/kg beta-FNA. A dose of 10.0 mg/kg beta-FNA completely antagonized the morphine discriminative stimulus, so that pigeons responded predominantly on the saline key up to doses of morphine that suppressed responding. Doses of beta-FNA that attenuated the effects of morphine had no effect on the discriminative stimulus effects of naltrexone. These results demonstrate that, like naltrexone, beta-FNA attenuates the discriminative stimulus effects of morphine in pigeons and, at sufficiently large doses, antagonizes morphine in an unsurmountable manner. Beta-FNA does not, however, share discriminative stimulus properties with naltrexone in these pigeons, and fails to attenuate the discriminative stimulus effects of naltrexone, lending support to the suggestion that naltrexone exerts discriminative stimulus effects under these experimental conditions predominantly by a non-mu opioid mechanism. PMID- 3107035 TI - Sequential changes in behavior induced by continuous infusions of amphetamine in rats. AB - Rats infused with amphetamine (0.65 mg/kg/h) for 5 days through Alzet (Tm) minipumps displayed a multiphasic sequence of behavioral changes. The behavior of the animals was characterized during daily 40-min test sessions in behavioral pattern monitors (BPM). Within 24 h after implantation of the minipumps, rats infused with amphetamine exhibited prolonged periods of oral stereotypies (licking or biting). By the 3rd day this stereotypy was replaced with locomotor and investigatory activation as the predominant response pattern. In addition, the magnitudes of tactile startle responses were reduced in a separate group of animals infused with amphetamine for 9 days. In accord with previous findings, dopamine (DA) in the corpus striatum was markedly reduced by the 3rd day, whereas DA in the nucleus accumbens was transiently increased. These results indicate that continuous infusion of amphetamine produces a relatively selective depletion of striatal DA resulting in a reduction in amphetamine-induced stereotypy with a corresponding increase in locomotor activation. PMID- 3107036 TI - Sex differences in nicotine's effects on consummatory behavior and body weight in rats. AB - Nicotine administration and cessation have greater effects on body weight and eating behavior in female than in male rats. These generalizations are based on studies of body weight and eating behavior for 2-3 week periods before, during, and after nicotine administration. Therefore, the sex differences may reflect differences in sensitivity to nicotine or simply differences in the time course of nicotine's effects. The present research was designed to replicate these previous studies and to examine long-term effects of nicotine cessation on body weight. Nicotine or saline was administered SC to female and male Sprague-Dawley rats for 16 days. Body weight, food consumption, and water consumption were measured before, during, and after nicotine administration. In addition, body weight was measured for 4 months after cessation of nicotine. There was an inverse relationship between nicotine and body weight. Also, there was an inverse relationship between nicotine and general consummatory behavior for females but not for males. The body weight of females that had received nicotine were indistinguishable from controls up to 4 months after cessation of nicotine. The body weight of males that had received 12 mg nicotine per kg per day remained lower than controls. PMID- 3107037 TI - Sex differences in the sensitivity of CBA mice to convulsions induced by GABA antagonists are age-dependent. AB - The administration of the GABA-blocking agents picrotoxin and bicuculline to adult (2.5-3 months old) CBA/HZgr mice resulted in the appearance of convulsions, the occurrence and/or lethality of which was greater in males than in females. The latency of picrotoxin-induced convulsions was also shorter in male mice. Strychnine, a drug which induces convulsions by blocking glycine receptors was equally effective in producing convulsions in both male and female adult mice. Unlike adult mice, young (20 days old) or old (2 years old) mice fail to display sex differences following the picrotoxin administration. Accordingly, the observed sex differences in the sensitivity of CBA mice to administration of convulsive agents are specific for the GABA system and present only in sexually mature, but not in immature or old animals. PMID- 3107038 TI - Effect of alcohol on rate of forgetting. AB - The effect of alcohol (1 ml per kg body weight) on the rate of forgetting was investigated using a continuous recognition memory paradigm. Subjects were required to make a speeded old/new response to each of 200 items presented sequentially on a computer screen. Ninety-five items appeared twice. The numbers of items intervening between the first and second occurrence were 1, 4, 9, 19 and 49 (19 of each). With alcohol, subjects were less sensitive (decreased d-prime) and more conservative (increased beta). Recognition speed and accuracy were both impaired by alcohol and by increasing numbers of intervening items. In addition, an interaction between the effects of alcohol and of delay on recognition accuracy indicates that the impairment of memory with alcohol can be at least partly attributed to faster forgetting. PMID- 3107039 TI - Different effects of chronic nicotine treatment regimens on body weight and tolerance in the rat. AB - The effect of different chronic nicotine administration regimens on body weight and the development of tolerance was examined in female rats. Groups of animals were either treated with nicotine via a subcutaneous continuous release pellet or via two injections each day of either a high (5.6 mg/kg) or low (0.8 mg/kg) dose. Both the Pellet and Low injection groups showed a progressive weight loss during nicotine treatment followed by a weight gain upon cessation of treatment, but the time course and size of these weight changes were quite distinct. In contrast, the High injection group gained weight during the 17 days of nicotine treatment. Tolerance, as measured by locomotor activity following an acute injection of nicotine 1 week after cessation of chronic nicotine treatment, was evident only in the Low injection group. This study demonstrates that the regimen in which nicotine is administered is an important factor in determining the behavioral effects produced by chronic nicotine treatment. PMID- 3107040 TI - Attenuation by pimozide of the suppressant effect of d-amphetamine on operant behaviour. AB - The interaction between pimozide (a selective D2-dopamine receptor antagonist) and d-amphetamine on the operant performance of rats maintained under variable interval schedules of positive reinforcement was examined. In Experiment 1, eight rats responded under variable-interval 30-s and variable-interval 300-s. Pimozide (0.0625, 0.125, 0.25, 0.5 mg/kg) suppressed performance maintained under both schedules in a dose-dependent manner, the degrees of suppression being equivalent in the two schedules. In Experiment 2, 12 rats responded under the same schedules. d-Amphetamine (0.1-3.2 mg/kg) suppressed performance under both schedules, the degree of suppression being somewhat greater in the case of variable-interval 30-s. Pre-treatment with pimozide (0.0625, 0.125 mg/kg) significantly attenuated the suppressant effect of d-amphetamine under both schedules. It is suggested that D2-dopamine receptors may be involved in mediating the suppressant effect of d-amphetamine on operant behaviour. PMID- 3107042 TI - L-dopa causes an acute, partial and reversible reversal of denervation-induced supersensitivity of striatal dopaminergic receptors. AB - Denervation-induced supersensitivity of the striatal dopamine receptors can be quantified by the turning behaviour induced by apomorphine. With this experimental model we found that high-dose L-dopa/carbidopa administration reduced this supersensitivity. This effect was seen on the 1st day and did not alter over 5 or 10 days of treatment, but disappeared when medication was discontinued. The degree of reduction was the same, independent of the dose and period of administration. This effect could provide a useful model for studying the phenomenon of the irreversibility of the supersensitivity of the striatal dopamine receptors. PMID- 3107043 TI - Home cage and test apparatus artefacts in assessing behavioural effects of diazepam in rats. PMID- 3107041 TI - Facilitation of latent inhibition by haloperidol in rats. AB - Latent inhibition (LI) is a behavioral paradigm in which prior exposure to a stimulus not followed by reinforcement retards subsequent conditioning to that stimulus when it is paired with reinforcement. Two experiments investigated the effects of 0.1 mg/kg haloperidol administration on LI as a function of number of CS pre-exposures. The investigation was carried out using a conditioned emotional response (CER) procedure consisting of three stages: pre-exposure, in which the to-be-conditioned stimulus, tone, was repeatedly presented without reinforcement; conditioning, in which the pre-exposed stimulus was paired with shock; and test, where LI was indexed by animals' suppression of licking during tone presentation. The three stages were conducted 24 h apart. In Experiment 1, 40 CS pre-exposures were given. LI was obtained in both the placebo and haloperidol conditions, but the effect was much more pronounced under the drug. Experiment 2 used ten CS pre exposures. LI was not obtained in the placebo animals but was clearly evident in animals injected with haloperidol. The implications of these findings for the effects of neuroleptics on learning are discussed. PMID- 3107044 TI - Poor bioavailability of CGS 8216 in a water/tween vehicle following intraperitoneal injection. PMID- 3107045 TI - New developments in long-term preventive therapy. AB - Lowering of standard serum lithium levels to 0.5-0.8 mmol/l has led to a marked reduction of side effects. Safety is increased through temporary discontinuation or dosage reduction of lithium in special risk situations. In unipolar but not in bipolar patients maintenance treatment with antidepressants is a valid alternative to lithium, and treatment choice may be determined by individual tolerance. Carbamazepine and valproate are worth trying in bipolar patients not responding to or not tolerating lithium. General principles for long-term preventive therapy are discussed. PMID- 3107048 TI - [Radiation physics and clinical aspects of whole body irradiation]. PMID- 3107047 TI - [Mutability of the germ cells of the progeny of irradiated male Drosophila]. AB - The increased frequency of random and radiation-induced mutation was registered in germ cells of drosophila irradiated male descendants of the first generation. The effect observed depended on of radiation dose delivered to parent males, test dose to progeny, type of mutation registered, and sex of the descendants under study. PMID- 3107046 TI - Effects of microwaves on three different strains of rats. AB - Confounding factors influencing the sensitivity of biological indicators of microwave exposure--lethality, colonic temperature (Tco), decreased body mass (dW), corticosterone (CS), thyrotropin (TSH), thyroxine (T4), free thyroxine (FT4), and prolactin (PRL) concentration--were studied in Long-Evans (LE), Wistar Kyoto (WKY), and spontaneous hypertensive (SHR) rats. The microwave signal was 2.45 GHz amplitude modulated at 120 Hz. Test power density ranged from 1 to 50 mW/cm2 for 2 h. In contrast to the LE and WKY rats, the SHR rats were characterized by intolerance (death) between 40 and 50 mW/cm2 (9.2 to 11.5 W/kg). The lowest lethal Tco was 41.1 degrees C. Survivors including all the LE and WKY rats were capable of maintaining Tco lower than 41.0 degrees C. In general, strain of rat seemed to influence other bioindicators and to interact with power density on these bioindicators. Except for Tco and PRL, baseline for the various bioindicators varied among the different strains of rats. Responses of T4 and FT4 were limited in magnitude and inconsistent among strains of rats. In general, the magnitude of Tco increase was more pronounced in SHR than in WKY. Differences between SHR and LE, however, could be noted only at 1, 10, and 50 mW/cm2. Increased Tco, increased magnitude of Dw, increased CS, decreased TSH, and increased PRL (stress reactions) could be noted in rats exposed to 30 mW/cm2 (approximately 6 W/kg) or higher, irrespective of strain. At least two of three strains of rats (WKY and SHR) exposed to 20 mW/cm2 (approximately 4 W/kg) showed changes in Tco, CS, TSH, and PRL. At 10 mW/cm2 (2 W/kg), increased Tco could be found in all three strains of rats accompanied by changes in dW and TSH in LE, TSH in WKY, and dW and CS in SHR. At 1 mW/cm2 (0.2 W/kg), increased Tco could be noted in two of three strains (LE and SHR) and increased PRL in LE only. The smallest Tco increases for a consistent response (increased magnitude of response with power density) were 1.59 degrees C for dW, 0.70 degrees C for CS, 0.24 degrees C for TSH, and 0.97 degrees C for PRL. Tentatively, the threshold intensity for response to microwave exposure for rats could be considered as 2 W/kg or a 0.24 degrees C increase at 24 degrees C ambient temperature. PMID- 3107050 TI - Skeletal proteins: significance in cell biology and pathology. PMID- 3107049 TI - Paraorbital tumors and tumor-like conditions: role of CT and MRI. AB - Tumors and tumor-like conditions of the paraorbital tissues that affect the eye usually require CT or MR imaging for complete evaluation. This article provides an overview of the wide variety of pathologic conditions to be considered when a paraorbital tumor is discovered or suspected. Some of the CT and MR imaging features of these disorders that aid in the differential diagnosis are reviewed. PMID- 3107051 TI - Decrease in the sialoglycoprotein content of the glomerular basement membrane in experimental nephrosis. AB - Phosphotungstic acid at low pH on glycolmethacrylate sections allows the detection of sialic acid groups in the lamina rara externa of the glomerular basement membrane. This staining procedure was used to study the alterations in puromycin aminonucleoside nephrosis and adriamycin nephrosis. In both model systems defects were detected in the sialic acid content of the lamina rara externa and the epithelial cell coat was also affected. The possible role of sialic acid in glomerular filtration is discussed. PMID- 3107053 TI - Alzheimer dementia: a study of the senile plaque with antisera and a monoclonal antibody specific for neurofilament proteins. PMID- 3107052 TI - Immunophotometric analysis of immunoglobulin synthesis and deposition in synovial membranes of patients with rheumatoid arthritis. AB - Immunophotometrical measurements of the Ig synthesis of plasma cells in joint capsules of patients with rheumatoid arthritis and osteoarthritis were compared. Patients with rheumatoid arthritis showed higher mean values in the single plasma cell than patients with osteoarthritis for all Ig isotypes except IgG. These results are indicative for a B cell activation with increased synthesis of Ig in RA. PMID- 3107054 TI - [The microquantitative distribution of alcohol dehydrogenase activity in the liver parenchyma of various mammals]. PMID- 3107055 TI - [Microscopic determination of glucose-6-phosphate dehydrogenase and malic enzyme in liver acinus]. PMID- 3107056 TI - Application of an automated image analyzer (TAS, Leitz Wetzlar) for morphometric analysis of peroxisomes in rat liver tissue. PMID- 3107058 TI - [Semi-automatic measurement of redox activity in single cells with a fluorescent formazan]. PMID- 3107057 TI - [Comparison of two red-emitting fluorochromes for their use in lectin histochemistry]. PMID- 3107059 TI - Autoradiographic investigations on sialoglycoconjugates in the CNS of normothermic and hibernating fat dormice (Glis glis). PMID- 3107060 TI - The cytoskeleton of rat aortic smooth muscle cells: normal conditions, experimental intimal thickening and tissue culture. PMID- 3107061 TI - Translocation of immunoglobulins across human epithelia: review of the development of a transport model. PMID- 3107062 TI - Biochemical micromethods. PMID- 3107063 TI - Scrapie and its association with 'amyloid-like' fibrils and glycoproteins encoded by cellular genes: an animal model for human dementia. PMID- 3107064 TI - Trachea and lung surgery in childhood. PMID- 3107065 TI - Pathophysiology of subglottic tracheal stenosis in childhood. AB - Two particularly problematic clinical entities are chosen from the many possible causes of the pathophysiology of subglottic tracheal stenoses in childhood: malformations of the "hard" and "soft" types of stenosis occurring typically as primary lesions; and stenoses caused by trauma (following intubation or faulty tracheostomy) as the most common secondary lesions. It is shown with reference to experimental investigations that subepithelial layers play the leading role in the origin of stenoses, in contrast to hitherto existing ideas based on clinical observations. Traumatic stenoses caused by unphysiological mechanical stressing show striking parallels to those in other age groups, suggesting the conclusion that a reaction of the mesenchymal tissue layers of the airway regions in question is a typical response to mechanical forces. PMID- 3107066 TI - Scimitar syndrome and associated pulmonary sequestration: report of a successfully corrected case. AB - A case of scimitar syndrome with pulmonary sequestration is reported. Anomalous pulmonary venous return from the right lung to the infradiaphragmatic vena cava inferior was diagnosed by pulmonary angiogram and sequestration of the right lower lobe was confirmed by aortogram. Venous return from the sequestrated lung was partly into the vena cava inferior and partly into the left atrium. Successful repair was achieved by resection of the sequestrated lobe and direct reimplantation of the scimitar vein into the left atrium. Accurate preoperative diagnosis and intraoperative evaluation of the anatomy is mandatory to correct this rare anomaly. PMID- 3107067 TI - Congenital cystic adenomatoid malformation of the lung. AB - The clinical and pathologic-anatomical picture of this rare lung malformation is described with reference to three cases from three different paediatric surgical hospitals. Methods of differential diagnosis against lung sequestration, pulmonary cysts, lobar emphysema, diaphragmatic hernia and pneumothorax are indicated. A definitive diagnosis and classification can be made only by means of histomorphological examinations. PMID- 3107068 TI - Experience in surgical treatment of pulmonary and bronchial tumours in childhood. AB - From the patient material of three paediatric surgical centres and the patient material of the paediatric surgical hospitals of Zurich, Switzerland and Leipzig, GDR, 24 cases of lung and bronchial tumours are reported. The aim of this review is to show a spectrum of the cases observed in our region. The most frequent of these very rare tumours was pulmonary blastoma, followed by endobronchial adenoma in its different variants. Since only the latter can be endoscopically diagnosed, endoscopy should be carried out as early as possible when the diagnosis is not clear. Cystic lung disease seems to be particularly frequently associated with pulmonary blastomas. Uncertainties in diagnosis and therapy owing to the rareness of these diseases cause further problems. PMID- 3107069 TI - Treatment of congenital cricoid stenosis. AB - Congenital cricoid stenosis is a rare malformation generally diagnosed at autopsy. Out of a total of fourteen cases reported by others, only five were treated successfully. Over a 10-year period, seven patients presented with congenital cricoid stenosis at the Sophia Children's Hospital in Rotterdam. On the basis of these numbers we surmise that this anomaly is less rare than is commonly thought. All seven patients were treated successfully. A new method of treatment is described, consisting of a combination of microsurgical laryngofissure and prolonged intubation with a new, low-friction, atoxic, soft, silicone rubber nasotracheal tube. The specially designed intubation material is also recommended for the treatment of iatrogenically damaged airways. The results indicate that this method constitutes a major advance not only in the treatment of cricoid stenosis but also in the treatment of damaged airways. PMID- 3107070 TI - Surgical correction of laryngotracheal stenoses in children. AB - A modified surgical technique according to Rheti is described: the cricoid and the uppermost tracheal rings are longitudinally dissected ventrally and dorsally. The enlargement of the lumen is stabilized by interposition of a notched piece of costal cartilage into the dissected posterior wall of the cricoid. A total of 63 children with laryngotracheal stenosis have been operated on by this method in Zurich since 1973 and in Munich since 1982. Laryngotracheal plasty is successful in over 80% of small children in whom the procedure is necessary. The voice becomes a little hoarse, but respiration is adequate, as demonstrated by our juvenile patients, some of whom have been decannulated for over 10 years. The earlier opinion that laryngoplasty performed in small children might impair laryngeal growth and result in severe stenoses has been disproved by the results presented. Our experience shows that prognosis is worse in children with tracheal stenosis and associated anomalies, such as paralysis of the vocal cord. PMID- 3107071 TI - Surgical treatment of congenital laryngotracheo-oesophageal cleft. AB - Laryngotracheo-oesophageal cleft has been considered a rare congenital anomaly, diagnosed when there is respiratory distress on feeding, associated with multiple congenital disorders. A tracheo-oesophageal fistula should be excluded. Diagnosis, even in skillful endoscopic hands, is difficult. Different approaches to surgical repair have been advocated in literature. Most authors prefer the lateral approach. Only 7 patients have reportedly been treated via the anterior approach. The anterior approach offers the advantage of excellent and also easy exposure of the anomaly. The theoretical disadvantage of postoperative laryngeal instability is not substantiated by experimental work (Calcaterra, Ann Otol 83:810-813, 1974), nor by our own clinical experience in six juvenile patients who underwent laryngofissure for other reasons. A further advantage of the anterior approach is that the laryngeal nerves are not jeopardized as in the lateral approach. We have treated 4 patients. Two patients have been treated successfully via a lateral pharyngotomy approach; each of them has a left recurrent nerve palsy. The other two patients were treated via a laryngofissure, one of them successfully; in the other patient the cleft has been closed with success, but the larynx is still stenosed by excessive mucous membrane folds. Cicatricial subglottic stenosis, which may occur postoperatively, and the frequently coinciding tracheomalacia, have been successfully treated with prolonged nasotracheal intubation with siliconized silicone rubber tubes. Four patients were treated successfully. Three other patients have come to our attention. As is often the case, this disorder seems to occur more frequently than was previously thought. PMID- 3107072 TI - Free periosteal grafts in tracheal reconstruction: an experimental study. AB - If resection followed by end-to-end anastomosis is not possible in obstructive lesions of the trachea other methods of reconstruction must be used. The ability of a periosteal graft to induce bone or cartilage formation when transplanted to cover a tracheal defect was confirmed in a previous experimental study. In this study free tibial periosteal grafts were used for repair of tracheal defects created in rabbits. The graft was placed circumferentially around the trachea. It is concluded that there is a high risk of development of severe osseous tracheal stenosis when periosteal grafts are placed circumferentially around the trachea. PMID- 3107073 TI - Tumour-induced intraluminal stenoses of the cervical trachea--tumour excision and tracheoplasty. AB - Three children with stenoses of the cervical trachea caused by tumours are reported on. The first was a 13-year-old girl with a sarcoma of the tracheal wall 20 cm down. We performed partial resection of the trachea and turned a skin flap according to Denecke into the defect. In the second case a capillary haemangioma had caused severe stenosis, requiring resection of the tumour together with the tracheal mucosa. A haemangioma had caused tracheal stenosis in the third case, too; in this child partial tracheal resection and skin flap plasty were performed. The postoperative course was uneventful in all three children. So far, there is no recurrence of the sarcoma 4 1/2 years after operation. PMID- 3107074 TI - Cardiopulmonary bypass in tracheal surgery in infants and small children. AB - Five resections of the distal trachea with cardiopulmonary bypass were carried out in four children aged 6 weeks to 24 months. Only technical aspects are discussed, and the operative method is described in detail. The use of cardiopulmonary bypass and heparinization of the patients did not cause any problems. Cardiopulmonary bypass allows an easy and unhurried procedure. Although other authors do not regard cardiopulmonary bypass as necessary in similar circumstances, we believe that it is the safest way of providing optimal operative conditions and results in surgery of distal tracheal stenoses. PMID- 3107075 TI - Resection of an intrathoracic tracheal stenosis in a child. AB - A 6-year-old boy sustained a severe head injury during a traffic accident. He was first treated at another hospital. Despite a short intubation period of only 3 days, within 4 weeks he developed severe tracheal stenosis, with a residual lumen 3 mm in diameter and a total length of 2.3 cm, ending 3 cm above the carina. After initial bougienage enlarging the lumen to 6 mm in diameter, surgery was performed at our hospital 6 weeks after the accident. The stenosis was resected in toto, and tracheal continuity was restored by interrupted sutures using the Grillo technique. The postoperative course was uneventful. Follow-up tracheoscopy 3 months later showed a residual stenosis of 20% within the anastomotic region, and the patient was free of symptoms. PMID- 3107077 TI - Long-distance resection of the trachea with primary anastomosis in small children. AB - While tracheal resection with primary anastomosis has been accepted as the therapy of choice for tracheal stenoses in adults since the 1960s, only 26 case reports are available on continuity resections of the trachea in children. The advantages of continuity resection include the one-stage procedure and the preservation of the natural wall structures. Anastomosis should be accomplished with pericartilaginous sutures and absorbable suture material. The increased tension on anastomoses inserted following resection of long tracheal segments does not necessarily have a negative influence on wound healing. The case histories of three small children are given in this report: they all underwent tracheal continuity resections involving four or five rings because of postintubation stenoses. The results of resection after up to 5 years' follow-up are very good, so that this method can be recommended in preference to the reconstructive tracheoplasty in children, which takes longer. If the cricoid cartilage is also involved a combination of tracheal resection and cricoid resection/dilatation is recommended. PMID- 3107076 TI - Treatment of tracheal stenoses by resection in infancy and early childhood. AB - An inquiry of Austrian paediatric and thoracic surgeons revealed six children aged 4 months to 5 years who had undergone circumferential resection of the trachea for congenital or acquired tracheal stenoses. Clinical data relating to these six Austrian cases are briefly presented. Experience shows that circumferential resection of localized tracheal stenoses can also be recommended for infants and young children. PMID- 3107078 TI - Subglottic stenosis in newborns after mechanical ventilation. AB - Mechanical ventilation in the neonatal period is sometimes followed by difficulty in removal of the endotracheal tube although the patient does not need further respiratory support. This problem results from subglottic stenosis consequent on prolonged use of endotracheal tubes. We found this complication in 5 patients among 854 newborns who required artificial respiration. A further patient was admitted from another hospital because of extubation problems. Our clinical diagnosis was confirmed by endoscopy. Drug therapy with steroids and anti inflammatory agents was tried in all six patients and was successful in two. In four patients conservative management failed and laser surgery was performed; three of these infants required tracheostomy. In two decannulation has already been performed at the age of 2 1/2 years. IN CONCLUSION: five of six patients were treated successfully, and one 3-year-old patient is still being treated. In the light of reports from other authors, this approach can be recommended for the management of acquired subglottic stenosis. PMID- 3107080 TI - Extralobar sequestration of the lung in children. AB - Sixteen patients with extralobar sequestration of the lung are reported on. The age at time of diagnosis varied from 21 days to 12 years (mean 3.6 years). Most of the patients presented with respiratory symptoms, such as dyspnoea, pneumonia, coughing attacks, cyanosis and asthmatic symptoms, but diagnosis was made incidentally in 4. Diagnosis was established by chest X-ray in every case. Preoperative angiography and bronchography was carried out in six cases. All 16 patients underwent thoracotomy for removal of the sequestration. Rudimentary bronchial remnants were found in 6 cases. Extralobar sequestration was associated with 12 additional malformations in 10 of the 16 patients. The clinical picture varies considerably and many of the "typical" features, such as systemic arterial blood supply, left lower lobe localization and diaphragmatic defect, are often absent. Diagnosis and treatment are easy. PMID- 3107081 TI - [Ceramidase (acylphingosinedeacylase)]. PMID- 3107079 TI - Clinical symptoms and therapy of lung separation. AB - This paper refers to the different terminology used in so-called lung separation/sequestration and to the standpoint of the pathologist. Theories of development are discussed. Clinical symptoms, diagnosis, indications for operation and operative technique are described, and nine cases of lung separation (six with extralobar and three with intralobar forms) tabulated analysed. Among them there is a 5-month-old female infant with extralobar lung separation in the right hemithorax resulting in recurrent pleural effusions with severe respiratory insufficiency. There was evidence of aeration in the pathohistological preparation. Pleural effusion and the origin of the aeration in the separated lung are discussed. PMID- 3107082 TI - Conversion of arachidonic acid into 12-oxo derivatives in human platelets. A pathway possibly involving the heme-catalysed transformation of 12-hydroperoxy eicosatetraenoic acid. AB - Analysis of arachidonic acid metabolites in human platelets by reverse-phase HPLC with radioactivity and UV detection revealed, besides Thromboxane B2 (TXB2), 12 hydroxy-heptadecatrienoic acid (HHT) and 12-hydroxy-eicosatetraenoic acid (12 HETE) previously described, two peaks of unidentified material absorbing at 280 nm. This material was purified by straight-phase HPLC and characterized by UV spectroscopy and gas chromatography-mass spectrometry. Three carbonyl compounds were identified: 12-keto-5,8,10,14-eicosatetraenoic acid and two geometric isomers of 12-oxo-5,8,10-dodecatrienoic acid. In a 5 min incubation at 37 degrees C in the presence of 9 microM arachidonic acid, the yield was of 0.5 to 1% of added arachidonic acid for the ketonic compound and of 4 to 7% for the sum of the two isomeric fatty acid aldehydes in comparison to 10 to 13% and 25 to 28% for TXB2 and 12-HETE, respectively. Because the three compounds carry a carbonyl group at position 12, their relationship with the 12-lipoxygenase pathway was investigated. It was found that the three compounds were formed when 12 hydroperoxy-eicosatetraenoic acid (12-HPETE) was incubated with intact or heat denaturated platelets or hemoproteins, strongly suggesting that these carbonyl compounds are products of a heme-catalysed transformation of 12-HPETE. PMID- 3107083 TI - Naturally occurring conjugated octadecatrienoic acids are strong inhibitors of prostaglandin biosynthesis. AB - Fatty acids from natural sources (mostly seed oils) were isolated and assayed for their effect on the bioconversion of arachidonic acid into prostaglandin E2, using sheep vesicular gland microsomes. Homologues and isomers of the naturally occurring fatty acids, obtained by chemical modification and/or organic synthetic methods, were also tested. Two very active cyclooxygenase inhibitors were discovered, namely jacarandic acid (8Z, 10E, 12Z-octadecatrienoic acid), isolated from Jacaranda mimosifolia, the concentration which gives 50% inhibition ([I]50) being 2.4 microM and the synthetic 8Z, 10E, 12E-octadecatrienoic acid, having an [I]50 of 1.0 microM. Under the conditions of the assay (75 microM substrate), earlier described potent inhibitors showed the following [I]50's: indomethacin: 1.3 microM; 9,12-octadecadiynoic acid: 1.3 microM, 8Z, 12E, 14Z-eicosatrienoic acid: 2.7 microM; 5,8,11,14-eicosatetraynoic acid: 4.4 microM. At a concentration of about half that of the substrate, the following naturally occurring fatty acids revealed inhibition ([I]50): columbinic acid (29 microM), calendulic acid (31 microM), liagoric acid (31 microM), ximenynic acid (39 microM), crepenynic acid (40 microM) and timnodonic acid (43 microM). Other fatty acids, and some of the above acids, were converted themselves more or less rapidly, mostly into conjugated monohydroxy fatty acids. PMID- 3107084 TI - Prostaglandin synthesis along the gastrointestinal tract of the rabbit: differences in total synthesis and profile. AB - In the present study we systematically investigated the synthesis of prostaglandins in the mucosa and the muscle layer along the length of the rabbit gut. Homogenates of mucosa and muscle layer were incubated with (14C)-labelled arachidonic acid, and prostaglandin formation was determined using thin-layer chromatography. With respect to total prostaglandin synthesis the highest values in the mucosa were measured in fundus, antrum and colon, whereas the prostaglandin synthesis in the muscle layer was maximal in the small bowel, particularly the ileum. In the mucosa, the prostaglandins E2 and F2a predominated, and there were minor differences along the gastrointestinal tract. In the muscle layer of the stomach, high amounts of 6-keto prostaglandin F1a, the stable degradation product of prostacyclin were produced, while small and large bowel homogenates synthesized mostly F2a. Consistently the prostaglandins A2/B2 were a major product in most locations. In addition, PG E2 catabolism to 15-keto PG E2 and 13,14-dihydro-15-keto PG E2 in the absence of NAD was slow. No significant changes in total prostaglandin synthesis and prostaglandin profile were detected between 24 hrs fasted and normally fed rabbits at any part of the gastrointestinal tract. PMID- 3107085 TI - Results of two randomised clinical trials of neutron therapy in rectal adenocarcinoma. PMID- 3107086 TI - Three-dimensional dose distributions for radiotherapy of sinus maxillary tumours. AB - Three-dimensional dose distributions for the radiation therapy of sinus maxillary tumours have been calculated. Irradiation techniques with 8 MV X-rays and 15 MV X rays from a linear accelerator (Siemens Mevatron 74 and Siemens Mevatron 77) and 60Co gamma-irradiation (Siemens Gammatron S80) are compared to each other. Using an anterior and a lateral field, the three-dimensional dose distribution of high energy photons shows that the radiation burden of the lens and the skin is significantly lower than with the use of 60Co irradiation. Sufficient dose coverage and sparing of the lens and the skin can be reached using the irradiation technique with 8 MV X-rays. PMID- 3107087 TI - What degree of accuracy is required and can be achieved in photon and neutron therapy? AB - In this paper an attempt is made to formulate criteria for the accuracy in the delivery of absorbed dose to a patient during photon or neutron therapy. These requirements are mainly based on the relative steepness of dose-effect curves for local tumour control and normal tissue damage. A review of these dose-effect curves after photon irradiation shows a great variety in steepness; the curves for normal tissue complications in general may be steeper than those for local tumour control. From these data a standard requirement for the combined uncertainty of type A (random) and type B (systematic), given as one relative standard deviation, in the absorbed dose delivery of 3.5% is proposed, even though it is known that in many cases larger values are acceptable and in a few special cases an even smaller value should be aimed at. From the available radiobiological and clinical data it can be concluded that no statistically significant difference can be observed in the relative steepness of dose-effect curves after photon or neutron irradiation. Similar limits will thus be requested in neutron therapy. The uncertainties in the various steps involved in the delivery of an absorbed dose to a point in a patient have been analysed for a treatment with two parallel-opposed beams. The results of this analysis showed that even for these simple treatment conditions, the required accuracy in the delivery of the absorbed dose cannot completely be obtained in photon therapy, and not nearly in neutron therapy. The uncertainties in physical, radiobiological and clinical approaches for weighting of the biological effectiveness of neutron radiation have been compared. The uncertainty in the RBE ratio will replace the type B uncertainty in the absorbed dose during patient treatment if the same dosimetry protocol is applied during biological and clinical procedures. PMID- 3107088 TI - Further investigations on neurotensin as central modulator of intestinal motility in rats. AB - Previous studies have shown that neurotensin (NT) administered intracerebroventricularly (i.c.v.) to rats provokes an inhibition of intestinal propulsion linearly related to the log of administered doses. In the present study it is demonstrated that, in contrast to morphine, repeated i.c.v. administrations of NT (2.5 nmol/rat/day) did not result in tolerance to the intestinal effect. Naloxone (Nx) administered i.c.v. fully antagonized the intestinal inhibition of i.c.v. morphine, but did not significantly alter the NT effect. However, centrally administered thyrotropin-releasing hormone (TRH) inhibited NT-induced (but not morphine-induced) intestinal inhibition. Direct microinjections of NT into the periaqueductal gray matter (PAG) produced complete inhibition of intestinal propulsion when the microinjections were localized in the dorsal portion. Finally, subdiaphragmatic vagotomy totally abolished the inhibition induced by NT into the PAG, while morphine was not affected. Some considerations are put forward concerning the existence in the central nervous system of a peptidergic pathway modulating intestinal function. PMID- 3107089 TI - Attenuation of polychlorinated biphenyls in soils. PMID- 3107091 TI - [Prevalence of high ALAT and serologic markers of hepatitis B virus in blood donors incriminated in non-A, non-B posttransfusion hepatitis]. PMID- 3107090 TI - [ABO and Rh distortions, in newborn brothers]. PMID- 3107092 TI - [Blood gases: methods of evaluation, interpretation]. PMID- 3107093 TI - [Evaluation of respiratory control]. PMID- 3107094 TI - Unresponsiveness of phospholipase C to the regulatory proteins Ns and Ni in pancreatic islets. AB - The possible participation of the regulatory proteins Ns and Ni in the regulation of phospholipase C activity in rat pancreatic islets was investigated. The islets were preincubated for 120 min with myo-[2-3H]inositol and the fractional outflow rate of [3H]inositol or production of [3H]inositol 1-phosphate was then measured. Glucagon failed to affect these metabolic variables, whether in the absence or presence of D-glucose. Pretreatment of the islets with cholera toxin also failed to affect basal or glucose-stimulated [3H]inositol outflow. Likewise, clonidine, which abolished insulin release evoked by D-glucose and carbamylcholine, failed to prevent the stimulant action of these secretagogues upon either [3H]inositol outflow or [3H]inositol 1-phosphate production. It is concluded that the regulatory proteins Ns and Ni apparently do not play any major role in the regulation of phosphoinositide phosphodiesterase activity in islet cells. PMID- 3107095 TI - Effects of esterase inhibitors and buthionine sulfoximine on the prevention of acetaminophen hepatotoxicity by N-acetylcysteine. AB - Mice poisoned with acetaminophen were treated with esterase inhibitors, buthionine sulfoximine, and N-acetyl-L-lysine in experiments designed to explore the mechanism of N-acetylcysteine protection in vivo. Three esterase inhibitors, phenylmethylsulfonyl fluoride, bis-(p-nitrophenyl)-phosphate, and diisopropylfluorophosphate, had no effect on the antidote effectiveness of N acetylcysteine, although each provided partial protection against acetaminophen poisoning. Buthionine sulfoximine, a specific inhibitor of gamma-glutamyl cysteine synthetase, antagonized the antidote effect of N-acetylcysteine. Acetaminophen-induced hepatotoxicity, as measured by plasma alanine aminotransferase activity, and mortality failed to decline, consistent with stimulation of glutathione synthesis as the primary mechanism of antidote protection. N-Acetyl-L-lysine was given at doses up to ten-fold higher than N acetylcysteine yet had no effect on acetaminophen hepatotoxicity or its prevention by N-acetylcysteine. These results advance the view that N acetylcysteine acts primarily as a glutathione precursor. They further suggest the esterase inhibitors limit poisoning by acetaminophen and may be useful agents in antagonizing the toxicity of other metabolically activated drugs. PMID- 3107096 TI - Plausible mechanism of inactivation of plasma alpha 1-proteinase inhibitor by acrolein. AB - Evidence is presented to show that inactivation of alpha 1-proteinase inhibitor caused by acrolein depends upon the modification of lysine and histidine residues. Approximately 90% activity was lost when twenty three lysine and eight histidine residues were modified. PMID- 3107097 TI - Intravitreal trifluorothymidine and retinal toxicity. AB - Intraocular trifluorothymidine was administered to one group of albino rabbits as an intravitreal injection, and to a second group of albino rabbits in the infusion solution during pars plana vitrectomy. The eyes of both populations were evaluated with preoperative and postoperative indirect ophthalmoscopy, electroretinography, and histologic examination. From these data, it was determined that an intravitreal injection of 200 micrograms/0.1 ml and a vitrectomy solution containing a concentration of 60 micrograms/ml trifluorothymidine were nontoxic to the rabbit eye. PMID- 3107098 TI - [A case of intermittent preexcitation syndrome using a Mahaim fiber]. PMID- 3107099 TI - Effects of carotid denervation on interactions between lung inflation and PaCO2 in modulating phrenic activity. AB - Hypercapnia attenuates the effects of static airway pressure (Paw) on phrenic burst frequency (f) and the expiratory duration. We examined the role of carotid chemoreceptors in this response using an experimental preparation that allowed independent control of lung inflation and CO2 reflexes. Experiments were conducted in intact (n = 6) and carotid denervated (CBX; n = 12) chloralose/urethane anesthetized dogs. Integrated phrenic amplitude (Phr), f, and the inspiratory (TI) and expiratory durations (TE) were measured as a function of Paw (2-12 cm H2O) at levels of PaCO2 between 30 and 80 mm Hg. In intact dogs: (1) f decreased as Paw increased, and elevated PaCO2 decreased the slope of this relationship; (2) neither PaCO2 nor Paw affected TI; and (3) TE increased hyperbolically with Paw, and elevated PaCO2 attenuated this relationship. In CBX dogs: (1) f decreased as Paw increased, but this relationship was not affected by PaCO2; (2) TI increased as PaCO2 increased but was unaffected by Paw; and (3) TE increased as Paw increased but was unaffected by PaCO2. The results indicate that carotid chemoreceptors are necessary in the mechanism whereby hypercapnia attenuates the effects of Paw on f and TE. Furthermore, carotid denervation reveals an effect of hypercapnia on TI, an effect that is not evident in dogs with functional carotid chemoreceptors. PMID- 3107100 TI - [Clinical course of cases of typhoid and paratyphoid A and B fevers in relation to the sensitivity of the causative agent to chloramphenicol]. PMID- 3107101 TI - [Anaphylactic shock due to highly purified porcine insulin]. PMID- 3107102 TI - [Colitis caused by Schistosoma mansoni]. PMID- 3107104 TI - [Microbiological study of urethritis in men]. PMID- 3107103 TI - [Metabolic balance of an enteral feeding formula in healthy subjects]. PMID- 3107105 TI - [Percutaneous endoscopic gastrostomy]. PMID- 3107106 TI - [Percutaneous endoscopic gastrostomy]. PMID- 3107107 TI - [Convulsive crises in elderly persons]. PMID- 3107108 TI - [Discontinuation of treatment in epileptic seizures in adolescence]. AB - A retrospective survey on the frequency of seizure-recurrence after drug withdrawal in all forms of adolescent seizures has been undertaken to detect possible prognostic criteria. Patients were selected according to 3 criteria: first seizure between 11 and 19 years of age; out-patients seen by one of us between 1955 and 1979 within the year of onset of epilepsy; all patients followed for at least 5 years after the first seizure. Two-hundred and seventy two patients entered the study. One-hundred and four patients (49 per cent) relapsed, most of them (83 per cent) within the first year after drug withdrawal. In univariate analysis, partial seizures, a normal initial EEG, an isolated seizure, a short length of illness, a long seizure-free period, one seizure only during the first year were significantly linked to a low relapse rate. The probability of being seizure-free after drug withdrawal was about 73 per cent in partial epilepsy, 20 per cent in idiopathic generalized epilepsy, and 36 per cent in undetermined generalized epilepsy. In patients having had a single seizure a dramatic difference was noted according to the seizure type: 12 per cent of relapses after a partial seizure, 69 per cent after a generalized seizure. Neither the age of onset of epilepsy nor the presence of an etiological factor were significant variables in predicting the outcome. When all factors were analysed simultaneously with Cox's hazard function, the type of seizure and the initial EEG appeared to be the only two independent factors significant for a risk of relapse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107109 TI - Dollars and sense of percutaneous biopsy demonstrates the cost effectiveness of the procedure. PMID- 3107110 TI - Cost-effectiveness ratio of chorionic villi biopsy for the prenatal diagnosis of chromosomal aberrations as compared with amniocentesis. AB - The observed cost of amniocentesis for the prenatal diagnosis of chromosomal aberrations in pregnancies at risk because of advanced maternal age was compared with the estimated cost of chorionic villi biopsy (CVB). The cost of CVB was estimated to be 22% less than that of amniocentesis when the cost of the sampling procedure, the laboratory charges and the cost of spontaneous and therapeutic abortions were considered. PMID- 3107111 TI - Do you still believe these myths about tube feeding? PMID- 3107112 TI - Duodenal diverticula demonstrated by endoscopic retrograde cholangio pancreatography (ERCP)--their relationship to biliary calculi and gastrooesophageal reflux. AB - In 24 patients with duodenal diverticula, demonstrated by ERCP, food-stimulated gastrooesophageal reflux was demonstrated in 33% of the patients and biliary tract calculi in 81%. This is in contrast to a previous study in patients with duodenal diverticula demonstrated by barium examination where gastroesophageal reflux occurred in 81% and biliary tract calculi in 38% of the patients. Differences in clinical selection are believed to be the underlying cause to these varying results. PMID- 3107113 TI - [Everyday life of the leukemic child]. PMID- 3107114 TI - [Aflatoxin M1 in type B milk solid in the municipality of Sao Paulo, SP (Brazil)]. PMID- 3107115 TI - Treatment of tinnitus with lidocaine and tocainide. AB - The efficacy of lidocaine and tocainide in the rational treatment of tinnitus aurium was evaluated in a double-blind randomized cross over study against saline as placebo. Forty patients with severe long lasting (more than six months) tinnitus and sensorineural hearing loss were included in the study. In 24 patients treated with lidocaine (loading dose: 3 mg/kg body weight in 10 min; maintenance dose: 1 mg/kg in 20 min), in 19 patients treated with tocainide infusion (750 mg in 30 min), and 10 patients treated with tocainide orally (400 to 2,400 mg per day), tinnitus intensity was reduced by more than 50%, compared with placebo (designated as a positive result). In some patients, ABRs showed prolongation of interpeak latencies (IPLs) indicating a retrochlear site of drug action. This hypothesis is supported by our own animal experiments with lidocaine in rabbits. IPLs showed a dose dependent reversible prolongation without hearing loss. PMID- 3107116 TI - A sensitive ELISA for von Willebrand factor (vWf:Ag). AB - A sensitive and precise enzyme-linked immunosorbent assay for the measurement of the von Willebrand factor (new nomenclature:vWf:Ag, previous name: F VIII:RAg) of plasma and factor VIII concentrates was constructed using a microtitre plate based sandwich technique. The coating antibody extracted vWf:Ag from standard and test material. Bound fraction was detected by a F(ab')2 peroxidase conjugate of the same antibody as used for coating. The sensitivity limit of the assay was 0.004 IU/ml, at least 10 times lower than the electro-immunoassay (EIA) using the same antibody, and better than any previously reported polyclonal ELISA for vWf:Ag. Imprecision between runs was 5.1% (CV%) at the 0.50 IU/ml level. Plasma from 30 healthy people gave 1.02 +/- 0.25 IU/ml (mean +/- 1SD) in the ELISA assay and 0.99 +/- 0.30 IU/ml (mean +/- 1SD) using electro-immunoassay (EIA) with a correlation coefficient of 0.967. Two cases of homozygous recessive von Willebrand's disease revealed vWf:Ag values at or below buffer blank in all dilutions. In 18 patients with type I von Willebrand's disease, a correlation coefficient of 0.899 was found comparing ELISA and EIA. All patients with variant von Willebrand's disease tested exhibited complete dose-response congruity of patient plasma and pooled standard plasma calibrated against the 1st International Standard for Plasma F VIII. Factor VIII concentrates also behaved like normal plasma in the assay. PMID- 3107117 TI - Selective expansion of a CD3+CD4-CD8- subpopulation in clinical groups associated with human immunodeficiency virus infection. AB - T lymphocytes (CD3+) without expression of CD4/CD8 surface antigens have recently been described in the thymus and peripheral lymphoid organs. We have conducted a retrospective analysis of the literature, seeking quantitative variations in this T-cell subset in normal heterosexual controls, and in risk, pre-AIDS, and AIDS groups, by means of the subtraction [CD3-(CD4+CD8]) and the ratio 100 X [CD3 (CD4+CD8])/CD3. Dramatic T lymphocytopaenia in AIDS patients and the progressive decay of CD4+ lymphocytes and increase of CD8+ lymphocytes throughout the clinical spectrum of HIV infection have been confirmed. Furthermore, we hereby demonstrate the selective expansion of CD3+CD4-CD8- lymphocytes, directly related to the clinical state in different clinical groups of infected people when compared with controls (P less than 0.05). The inverse relationship between the CD3+CD4-CD8- cell subset and other mature T-cell subsets, mainly CD4+ (r = -0.49; P less than 0.01), suggests the existence of mutual regulatory interactions. These in vivo results, which are in agreement with those obtained in long-term infected cultures, cannot be explained by direct cytopathic effects of the virus on the very few infected cells. Thus, the implication of the expansion of these functional precursors on the prognosis for infected people, and the paradoxes of the immunodeficiency, such as lymphoproliferation and autoimmune features, are discussed. PMID- 3107118 TI - Characterization of amyloid proteins AA and SAA as apolipoproteins of high density lipoprotein (HDL). Displacement of SAA from the HDL-SAA complex by apo AI and apo AII. AB - An AA-like protein with a molecular weight of 8600 complexed to high-density lipoprotein (HDL) was demonstrated in several acute-phase sera with high levels of SAA. The protein 'apo AA' (to distinguish it from tissue AA) was isolated by elution from sodium dodecyl sulphate (SDS)-polyacrylamide gel, and showed antigenic identity with purified tissue protein AA in double immunodiffusion. Normal HDL was shown to bind purified tissue AA in vitro. When the in vitro associated HDL-AA complexes were given intravenously to mice during induction of amyloidosis, human AA was incorporated in the amyloid fibrils. Both apo AI and apo AII were shown to displace SAA from acute phase HDL when added to HDL-SAA complexes in vitro. This might be of importance in amyloidogenesis, as the liver and the small intestine, which are the main sites for AI and AII synthesis, are also sites of early amyloid deposition. PMID- 3107119 TI - A novel arachidonic acid metabolite with stimulatory effect on PHA-induced mitogenesis of lymphocytes. AB - The isolation of a novel arachidonic acid (Aa) metabolite from the supernatant of unstimulated human cord blood mononuclear leucocytes is reported. The metabolite, arbitrarily named 'compound 4' is neither a known lipoxygenase nor a cyclooxygenase product. 'Compound 4' was added to PHA-stimulated peripheral blood mononuclear leucocytes (PBML) from healthy blood donors, from mothers at term and from patients with immunodeficiency. 'Compound 4' induced an increase in the 3H TdR incorporation by the maternal PBML and by the PBML from patients with various immunodeficiencies such as Wiskott-Aldrich syndrome and common variable immunodeficiency, whereas it had no effect on the proliferation of PBML from blood donors. PMID- 3107120 TI - [Hemodynamic effects of an osmotic bolus for the reversible opening of the blood brain barrier]. AB - Reversible opening of the blood-brain barrier before administration of watersoluble cytoreductive agents constitutes a new tool in the treatment of central nervous malignancies. In this study a volume of 172 ml mannitol 25% has been injected into one of the cerebral arteries within 30 seconds. 5 minutes later the osmolality had augmented from 286 to 303 mosmol/kg and the plasma volume by 15%. The hemodynamic measurements--cardiac index (+47%), heart rate (+7%), LVSWI (+50%), systemic vascular resistance (-20%) and blood volume (+15%)- indicate a biphasic response with early fall in SVR followed by a rise in cardiac performance which is independent of the preload. PMID- 3107121 TI - [A new group of gastrointestinal viruses ("Toroviridae")]. PMID- 3107122 TI - Insulin rapidly increases diacylglycerol by activating de novo phosphatidic acid synthesis. AB - The mechanisms whereby insulin increases diacylglycerol in BC3H-1 myocytes were examined. When [3H]arachidonate labeling of phospholipids was used as an indicator of phospholipase C activation, transient increases in [3H]diacylglycerol were observed between 0.5 and 10 minutes after the onset of insulin treatment. With [3H]glycerol labeling as an indicator of de novo phospholipid synthesis, [3H]diacylglycerol was increased maximally at 1 minute and remained elevated for 20 minutes. [3H]Glycerol-labeled diacylglycerol was largely derived directly from phosphatidic acid. Insulin increased de novo phosphatidic acid synthesis within 5 to 10 seconds; within 1 minute, this synthesis was 60 times greater than that of controls. Thus, the initial increase in diacylglycerol is due to both increased hydrolysis of phospholipids and a burst of de novo phosphatidic acid synthesis. After 5 to 10 minutes, de novo phosphatidic acid synthesis continues as a major source of diacylglycerol. Both phospholipid effects of insulin seem important for generating diacylglycerol and other phospholipid-derived intracellular signaling substances. PMID- 3107123 TI - Primary structure and biochemical properties of an M2 muscarinic receptor. AB - A partial amino acid sequence obtained for porcine atrial muscarinic acetylcholine receptor was used to isolate complementary DNA clones containing the complete receptor coding region. The deduced 466-amino acid polypeptide exhibits extensive structural and sequence homology with other receptors coupled to guanine nucleotide binding (G) proteins (for example, the beta-adrenergic receptor and rhodopsins); this similarity predicts a structure of seven membrane spanning regions distinguished by the disposition of a large cytoplasmic domain. Stable transfection of the Chinese hamster ovary cell line with the atrial receptor complementary DNA leads to the binding of muscarinic antagonists in these cells with affinities characteristic of the M2 receptor subtype. The atrial muscarinic receptor is encoded by a unique gene consisting of a single coding exon and multiple, alternatively spliced 5' noncoding regions. The atrial receptor is distinct from the cerebral muscarinic receptor gene product, sharing only 38% overall amino acid homology and possessing a completely nonhomologous large cytoplasmic domain, suggesting a role for the latter region in differential effector coupling. PMID- 3107124 TI - A small viral RNA is required for in vitro packaging of bacteriophage phi 29 DNA. AB - A small RNA of Bacillus subtilis bacteriophage phi 29 is shown to have a novel and essential role in viral DNA packaging in vitro. This requirement for RNA in the encapsidation of viral DNA provides a new dimension of complexity to the attendant protein-DNA interactions. The RNA is a constituent of the viral precursor shell of the DNA-packaging machine but is not a component of the mature virion. Studies of the sequential interactions involving this RNA molecule are likely to provide new insight into the structural and possible catalytic roles of small RNA molecules. The phi 29 assembly in extracts and phi 29 DNA packaging in the defined in vitro system were strongly inhibited by treatment with the ribonucleases A or T1. However, phage assembly occurred normally in the presence of ribonuclease A that had been treated with a ribonuclease inhibitor. An RNA of approximately 120 nucleotides co-purified with the phi 29 precursor protein shell (prohead), and this particle was the target of ribonuclease action. Removal of RNA from the prohead by ribonuclease rendered it inactive for DNA packaging. By RNA-DNA hybridization analysis, the RNA was shown to originate from a viral DNA segment very near the left end of the genome, the end packaged first during in vitro assembly. PMID- 3107125 TI - Bacterial resistance to beta-lactam antibiotics: crystal structure of beta lactamase from Staphylococcus aureus PC1 at 2.5 A resolution. AB - beta-lactamases are enzymes that protect bacteria from the lethal effects of beta lactam antibiotics, and are therefore of considerable clinical importance. The crystal structure of beta-lactamase from the Gram-positive bacterium Staphylococcus aureus PC1 has been determined at 2.5 angstrom resolution. It reveals a molecule of novel topology, made up of two closely associated domains. The active site is located at the interface between the domains, with the key catalytic residue Ser70 at the amino terminus of a buried helix. Examination of the disposition of the functionally important residues within the active site depression leads to a model for the binding of a substrate and a functional analogy to the serine proteases. The unusual topology of the secondary structure units is relevant to questions concerning the evolutionary relation to the beta lactam target enzymes of the bacterial cell wall. PMID- 3107126 TI - Allelic exclusion in transgenic mice that express the membrane form of immunoglobulin mu. AB - Antibody-producing cells display a special form of regulation whereby each cell produces immunoglobulin from only one of its two sets of antibody genes. This phenomenon, called allelic exclusion, is thought to be mediated by the product of one heavy chain allele restricting the expression of the other. Heavy chains are synthesized in two molecular forms, secreted and membrane bound. In order to determine whether it is specifically the membrane-bound form of the immunoglobulin M (IgM) heavy chain (mu) that mediates this regulation, transgenic mice were created that carry a human mu chain gene altered so that it can only direct the synthesis of the membrane-bound protein. The membrane-bound form of the human mu chain was made by most of the B cells in these animals as measured by assays of messenger RNA and surface immunoglobulins. Further, the many B cells that express the human gene do not express endogenous mouse IgM, and the few B cells that express endogenous mouse mu do not express the transgene. Thus, the membrane-bound form of the mu chain is sufficient to mediate allelic exclusion. In addition, the molecular structures recognized for this purpose are conserved between human and mouse systems. PMID- 3107127 TI - Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. AB - Gamma interferon (IFN-gamma) and B cell stimulatory factor-1 (BSF-1), also known as interleukin-4, are T cell-derived lymphokines that have potent effects on B cell proliferation and differentiation. They are often secreted by distinct T cell clones. It is now shown that IFN-gamma stimulates the expression of immunoglobulin (Ig) of the IgG2a isotype and inhibits the production of IgG3, IgG1, IgG2b, and IgE. By contrast, BSF-1 has powerful effects in promoting switching to the expression of IgG1 and IgE but markedly inhibits IgM, IgG3, IgG2a, and IgG2b. These results indicate that BSF-1 and IFN-gamma as well as the T cells that produce them may act as reciprocal regulatory agents in the determination of Ig isotype responses. The effects of IFN-gamma and BSF-1 on isotype expression are independent. PMID- 3107128 TI - Tissue-specific expression of functionally rearranged lambda 1 Ig gene through a retrovirus vector. AB - To explore the potential use of retrovirus vectors for the transfer of genomic DNA sequences into mammalian cells, recombinant retroviral genomes were constructed that encode a functionally rearranged murine lambda 1 immunoglobulin gene. Several of these genomes could be transmitted intact to recipient cells by viral infection, although successful transmission depended both on the orientation of the lambda 1 sequences and on their specific placement within vector sequences. The lambda 1 gene transduced by viral infection was expressed in a cell lineage-specific manner, albeit at lower levels than endogenous lambda 1 gene expression in cells from the B-lymphocyte lineage. Vectors yielding integrated proviruses that lacked viral transcriptional enhancer sequences were used to show that neither viral transcription nor the viral transcriptional sequences themselves had any effect on the tissue specificity of lambda 1 gene expression or the absolute amount of lambda 1 transcription. Vector transcription did, however, dramatically decrease the amount of lambda 1 protein that could be detected in tranduced cells. These results suggest that retrovirus vectors may be useful reagents not only for the expression of complementary DNA sequences but also for studies of tissue-specific transcription in mammalian cells. PMID- 3107129 TI - The earliest "humans" were more like apes. PMID- 3107130 TI - Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. AB - Linkage analysis of 15 Utah kindreds demonstrated that a gene responsible for von Recklinghausen neurofibromatosis (NF) is located near the centromere on chromosome 17. The families also gave no evidence for heterogeneity, indicating that a significant proportion of NF cases are due to mutations at a single locus. Further genetic analysis can now refine this localization and may lead to the eventual identification and cloning of the defective gene responsible for this disorder. PMID- 3107132 TI - Micro-organisms in agriculture. PMID- 3107131 TI - The spectrum of skeletal changes associated with long-term administration of 13 cis-retinoic acid. AB - The roentgenographic changes noted in 13 patients, who had been treated with long term 13-cis-retinoic acid for inherited scaling disorders, are presented. These patients were aged 13-16 years and had received this therapy for 16-87 months (mean, 58 months). The most pronounced abnormality was osteophyte formation, particularly in the cervical spine. Other changes which were noted included ossification of the anterior longitudinal and atlanto-occipital ligaments, proliferative enthesopathies, diminished bone density, premature fusion of epiphyses, and modeling abnormalities. Six of the 13 patients were asymptomatic and the osseous manifestations of this therapy were identified only by roentgenographic evaluation. PMID- 3107133 TI - Probiotics. PMID- 3107134 TI - The role of micro-organisms in the dairy industry. PMID- 3107135 TI - Current progress in reducing salmonella colonization of poultry by 'competitive exclusion'. PMID- 3107136 TI - The ecology of drug resistance in enteric bacteria. PMID- 3107137 TI - Mastitis, the non-antibiotic approach to control. PMID- 3107138 TI - Chronic pain and depression. AB - Patients with chronic pain syndromes often have concomitant depression. In this paper we discuss the clinical and biologic characteristics of depression, and also briefly discuss the various subtypes of depression, potential modes in the development of depression, neuroendocrine markers of depression, and patient response to antidepressant medication. PMID- 3107140 TI - [Hemosorption in severe diabetic ketoacidosis]. PMID- 3107141 TI - Absolute left ventricular volume changes after sublingual nitroglycerine and nifedipine intervention. AB - The haemodynamic effects of two vasodilators, sublingual nitroglycerine and nifedipine, on absolute end-diastolic volume, end-systolic volume, stroke volume (SV), heart rate, systolic blood pressure (SBP), cardiac output (CO) and corresponding cardiac indices were measured in two different groups, each consisting of 20 ischaemic heart disease patients, with gated blood pool scintigraphy. A control study was done in 5 ischaemic heart disease patients without intervention. Direct measurement of left ventricular (LV) volume was done by correcting LV activity for tissue attenuation utilising a geometric method. With nifedipine intervention only SBP (125.25 +/- 19.8 mmHg) showed a significant mean decrease (11 mmHg). The other measured parameters did not change significantly. With nitroglycerine all the parameters except LV ejection fraction showed significant changes. Mean CO decreased by 8% while mean SV decreased by 16%. The results in the control group showed excellent repeatability. The absolute haemodynamic changes of future cardiac drugs might easily be measured in vivo by this non-invasive technique. PMID- 3107142 TI - A method for securing nasogastric tubes in unco-operative patients. AB - A method for securing nasoenteric tubes in the unco-operative patient is presented. It may help reduce the complications associated with these devices from the need to replace them or from incorrect positioning. PMID- 3107139 TI - A serological survey of scrub, tick, and endemic typhus in Sabah, East Malaysia. AB - A seroepidemiological survey of 837 people and 383 febrile patients was performed in rural areas of Sabah. We determined that the rickettsial diseases scrub typhus and endemic typhus were uncommon causes of febrile illness, as was tick typhus, except in forest dwelling peoples. The rate of occurrence of SFGR specific antibody was 16.5% among 412 forest dwellers, indicating that tick typhus may be a frequent cause of illness in this population. PMID- 3107143 TI - The anatomic basis of the fascio-cutaneous flap of the posterior interosseous artery. AB - The authors present a study of the surgical anatomy of the posterior interosseous artery (PIA) in 70 cases to establish the anatomic basis of a new forearm fascio cutaneous flap, the posterior interosseous flap which has been described by one of the authors (AC Masquelet). The PIA was verified in every case. Its course corresponds to a line drawn from the lateral epicondyle of the humerus to the head of the ulna, i.e. to the septum between the extensor carpi ulnaris and extensor digiti minimi proprius muscles. The artery, whose average caliber is 1.7 mm, gives off 7 to 14 cutaneous branches in its course. The point of emergence of the artery in the posterior aspect of the forearm corresponds to the junction between the upper and middle thirds of the line from the epicondyle and the ulnar head. The PIA anastomoses with the anterior interosseous artery and the dorsal carpal network in 98.6% of cases. The artery remains closely related to the deep branch of the radial nerve and is crossed by the branches of this nerve to the extensor carpi ulnaris muscle. The cutaneous distribution of the PIA extends from elbow to wrist, centered on the epicondylarulnar line, with an average breadth of 5 cm. Twelve operations have already been performed using the posterior interosseous flap, 2 with a direct pedicle and 10 with a retrograde pedicle, and all survived completely. PMID- 3107144 TI - Anatomic basis of Arnold's ear-cough reflex. AB - A clinical survey of 500 patients revealed 4.2% incidence of Arnold's ear-cough reflex. The reflex was bilateral in 2.8% of the patients. It was also elicitable from the anterior meatal wall in 2% of the patients, thus questioning the classically taught distribution of Arnold's nerve. Arnold's nerve also mediates the auriculo-palatal, auriculo-lacrimal, auriculo-cardiac and the ear-vomiting reflexes; but these are less apparent and not so commonly encountered. PMID- 3107145 TI - Cross-sectional anatomy of the pericardial sinuses, recesses, and adjacent structures. AB - Detailed drawings of four cross sections through the mediastinum which pass through the sinuses and recesses of the pericardial cavity, are presented. The drawings depict the location and extent of the pericardial sinuses, recesses, and their closely associated extrapericardial structures. Two previously unnamed recesses within the serous pericardium are defined and named, one the inferior aortic recess of the transverse sinus and the other, the right pulmonic recess of the transverse sinus. The terminology of the pericardial sinuses and recesses has been inconsistent, and the authors propose a nomenclature for standardizing the names of the recesses of the serous pericardium. Important anatomic pericardial relationships with regard to pericardial effusions and lymphadenopathy are discussed. PMID- 3107146 TI - Morphology of the middle rectal arteries. A study of 30 cadaveric dissections. AB - The middle rectal arteries were studied in 30 cadavers of adult and older individuals (29 Caucasians and one Negro) of both sexes (15 males and 15 females). The middle rectal artery was present in 56.7% of the cases, bilaterally (36.7%) or unilaterally (20%), originating from the internal pudendal (40%), inferior gluteal (26.7%), internal iliac (16.8%), and less frequently from other pelvic branches. The average external diameter of the middle rectal artery was found to be 1.7 mm, its average length about 7 cm, and the point of penetration in the rectal wall about 6 cm (average) superior to the anus. The most frequent sites of the rectal wall pierced by the middle rectal arteries were the anterior (50% of the cases) and posterior (45%) quadrants of the rectum, whether isolated or combined (43.3%). These anatomical features justify, when needed and possible, the preservation of the middle rectal artery in surgical interventions on related organs. The term middle rectal arteries in Nomina Anatomica should be changed to inferior rectal arteries and indented under internal pudendal artery; the current term inferior rectal arteries should be changed to anal arteries to follow the already adopted division of the terminal intestine into rectum and anal canal. PMID- 3107147 TI - The inferior alveolar artery in its bony course. AB - Based on the dissection of 30 hemi-mandibles, the authors report a study of the inferior alveolar artery in its intraosseous course. On morphologic considerations they propose a classification of the collaterals into two groups: the principal collaterals destined for the teeth and the bony alveolar tissue and the secondary collaterals destined for the sheath and the nerve as well as the bony tissue around the canal. Loss of the teeth and absorption of the alveolar bone modify the caliber of the inferior alveolar arterial axis, the distribution of its collaterals and possibly its mode of termination. These facts suggest a consideration of the vascularization of the mandible in terms of four sectors. They arrive at practical conclusions that may be drawn from this study in stomatology. PMID- 3107148 TI - The left recurrent laryngeal nerve at birth: anatomy and surgical applications. AB - The aim of this study was to define the origin, course, caliber and relations of the left recurrent laryngeal nerve (N Laryngeus recurrens) in order to localize the nerve during surgery for esophageal atresia. Eighteen anatomic specimens were dissected and 12 surgical cases were analysed. Left recurrent laryngeal nerve palsy after this particular form of neonatal surgery is a very real risk. It seemed useful to describe an anatomic technique of identifying the nerve in the mediastinum during such surgery, in order to prevent this complication. PMID- 3107149 TI - Anatomic study of the lateral cutaneous rami of the subcostal and iliohypogastric nerves. AB - On the supposition that some "pseudocoxalgias" might be due to a neuralgia of the lateral rami leaving the subcostal and iliohypogastric nerves above the lateral edge of the iliac crest, the authors undertook an anatomic study of their pathways and pattern of distribution. These rami supplying the skin below the iliac crest, which they cross close together, the ramus arising from the subcostal nerve by perforating the internal and external oblique abdominal muscles, that arising from the iliohypogastric nerve a little lower, creating a bony groove palpable in thin subjects and transformed into an osseomembranous tunnel by the aponeurosis of these muscles. This arrangement may give rise to an entrapment syndrome. At this intersection, the course is either vertical or "bayonet-shaped", directly subcutaneous, and hence exposed to possible friction and microtraumata (tight clothes). The two rami are of unequal length. Frequently, the ramus arising from the subcostal nerve is short, not exceeding 10 cm, below the iliac crest, thus corresponding to the usual description. That arising from the iliohypogastric nerve descends further, passing 3 to 5 cm anterior to the great trochanter. It ends either at this level or 8 to 10 cm below. This accounts for the distribution of the pain felt when there is irritation of this ramus. PMID- 3107150 TI - Radio-anatomic study of the carotid axis with regard to the implantation of microsurgical vascular anastomoses. AB - The authors report a radio-anatomic study of the carotid axis in the context of the implantation of microsurgical vascular anastomoses. The information derived from 36 dissections and 50 arteriographic studies suggests the preferential use of the superior thyroid, facial and lingual branches. Section and turning-down of the external carotid and direct end-to-side implantation on the common carotid could provide fall-back solutions when the collaterals are slender. Because of anatomic variations and frequent atheromatous lesions, arteriographic study before implantation appears essential. PMID- 3107151 TI - Simplified endoscopic photography for anatomic correlation with CT and MR of the larynx and pharynx. AB - Improvements in photographic film and the availability of fluid light transmitters rather than fibro-optics permit endolaryngeal and nasopharyngeal photography to be conducted using the same light levels as simple diagnostic examinations of these areas. The added perspective of endoscopic examination can often clarify many confusing bulky lesions that distort CT and MR anatomy. Thus endoscopic photography is a tremendous teaching tool. PMID- 3107152 TI - A rare cause of acromegaly: ectopic production of growth hormone-releasing factor by a bronchial carcinoid tumor. AB - Ectopic production of growth hormone-releasing factor (GRF) is a rare cause of acromegaly. In addition to its production by gangliocytomas, both hypothalamic and intrasellar, in rare cases various neuroendocrine neoplasms produce the substance, with resultant growth hormone cell hyperplasia of the pituitary and acromegaly. We report an endocrinologically well-documented case of a GRF producing bronchial carcinoid tumor in which the associated acromegaly was cured by lobectomy. PMID- 3107153 TI - Histopathologic investigation of a case of meningioangiomatosis not associated with von Recklinghausen's disease. AB - A case of meningioangiomatosis not associated with von Recklinghausen's disease is reported. Microscopically, irregularly branched blood vessels extending into the gray matter from the meningeal surface are surrounded by a concentric arrangement of proliferating spindle-formed cells. Ultrastructurally these proliferating cells are composed of elongated heterochromatin-rich nuclei and slender cytoplasm-containing microfilaments, occasionally associated with desmosomal junctions and basal laminalike structures. Judging from these findings, together with a negative immune reaction for S-100 protein, the histogenesis of these proliferating cells is most probably meningothelial in origin. PMID- 3107154 TI - Ocular involvement in the fetal alcohol syndrome. AB - Maternal alcohol abuse during pregnancy causes malformations of the eyes with serious consequences to the vision of the affected children. A high percentage (up to 90%) of children suffering from the fetal alcohol syndrome have eye abnormalities, including malformation in the outer eye region, disorders of motility, and defects of different intraocular structures. Two kinds of malformations stand out as most typical--hypoplasia of the optic nervehead (up to 48%) and increased tortuosity of the retinal vessels, especially of the arteries (up to 49%). Visual acuity is often moderately or severely reduced. Considering the developmental timing of different tissues of the eye, one can presume that there is a risk for deleterious effects of alcohol on eye structures at any point of time from early gestation until development is completed. PMID- 3107155 TI - Canine islet autografts with and without administration of cyclosporine. AB - Cyclosporine administration prolongs the survival of immediately vascularized allografts. However, its role in the prevention of rejection of dispersed pancreatic islet allografts is uncertain, and some studies have suggested that it may be harmful. We performed total pancreatectomies in 21 mongrel dogs, followed by intrasplenic autotransplantation of islet-enriched, dispersed pancreatic tissue prepared by means of ductal perfusion and collagenase digestion. Ten dogs received no other therapy (controls) and 11 received orally administered cyclosporine from the day before to 30 days after transplantation. Therapeutic blood levels of cyclosporine were documented by means of high-pressure liquid chromatography. There was no difference in engraftment in six of 10 controls, and eight of 11 cyclosporine-treated dogs remained normoglycemic for more than 30 days. Intravenous glucose tolerance test results (K values), fasting serum insulin levels, and insulin secretion in response to a glucose challenge were similar in the two groups. There were two late treatment failures in the control group and one in the cyclosporine-treated group. We were unable to detect an adverse effect of cyclosporine on the engraftment or function of canine islet autografts. We conclude that cyclosporine remains a promising drug for use in studies of islet transplantation in human beings. PMID- 3107156 TI - [Regional peptic acid activity in gastroduodenal ulcers]. AB - The acid peptic activity in different parts of the gastroduodenal area using an original method was investigated in 25 patients with duodenal ulcer, 39 patients with gastric ulcer and 14 controls. Acidity and proteolytic activity in the gastroduodenal area were different and correlated with morphofunctional peculiarities of the mucosa. The acid peptic activity in the zone of ulceration in mediogastric and anthropyloric ulcers did not exceed that in persons without gastroduodenal pathology. The acid peptic activity in the proximal part of the duodenum was higher in the patients with duodenal ulcer than in the controls. PMID- 3107157 TI - [Functiono-morphologic substantiation of the diagnostic value of the atropine test in patients with duodenal ulcer]. AB - The basal production of hydrochloric acid, pepsin, the level of immunoreactive gastrin-17 in the blood serum and gastric juice, endocrine G-, EcI- and Ec-cells of the gastric mucosa were studied in 42 patients with duodenal peptic ulcer. Patients with a negative atropine test were characterized by a high production of hydrochloric acid, hypergastrinemia, an elevated secretion of gastrin with gastric juice, hyperplasia of G- and EcI-cells. In a positive atropine test these indices were lower with the exception of a great amount of Ec-cells in the antral mucosa. Thus the atropine test reflected the functional-morphological arrangement of the secretory apparatus of the gastric mucosa and was of diagnostic value. PMID- 3107158 TI - [Effect of indomethacin on basic parameters of gastric secretion, aggregative activity of blood platelets and fibrinolysis]. AB - Indomethacin at a therapeutic dose of 50 mg causes a significant increase in the basal and histamine-stimulated acid and pepsin secretion, a decrease in bicarbonate production, the suppression of ADP-induced platelet aggregation and antiaggregational activity of the vascular epithelium, and intensification of fibrinolysis at the expense of activation of its first phase. These effects determined by the blockade of prostaglandin cyclooxygenase, can contribute to the development of erosive-ulcerative hemorrhagic lesions of the gastroduodenal mucosa. The sensitivity of different people to indomethacin varies within broad limits. A study of a response of the thromboxan-prostacycline system to the drug administration can serve for objective assessment of individual drug tolerance, prognosis of complications and a choice of an effective therapeutic scheme. PMID- 3107160 TI - Factor VIII coagulant moiety binds to platelets by binding to phospholipids of the platelet membrane. AB - Washed human platelets were incubated with commercial factor VIII concentrate, or with purified factor VIII coagulant moiety. Platelets were then washed again and lysed by sonication. VIII:Ag and vWf:Ag were measured in the platelet lysate prior to and after incubation of the lysate with phospholipase C (PL-C). Platelet bound VIII:Ag was significantly higher after incubation of washed platelets with factor VIII concentrate than after incubation with buffer. Platelet bound VIII:Ag was further increased when platelets had been incubated with concentrate in the presence of thrombin and collagen. In contrast, only a slight increase in platelet bound vWf:Ag was observed after incubation of platelets with concentrate. When washed platelets had been incubated with factor VIII coagulant moiety, also significantly more platelet bound VIII:Ag was observed than after incubation with buffer. Measurable VIII:Ag, but not vWf:Ag, increased significantly after incubation of the platelet lysate with PL-C. When intact washed platelets had been treated with PL-C prior to the incubation with concentrate, binding of VIII:Ag to platelets was nearly completely abolished. Our data suggest that the factor VIII coagulant moiety binds to phospholipids of the platelet membrane and thereby contributes to the assembly of the factor X activating complex on the platelet surface. PMID- 3107161 TI - The outcome of idiopathic Bence Jones proteinuria. AB - The authors studied two patients with idiopathic Bence Jones proteinuria (BJP) that fulfill all the criteria proposed by Kyle and Greipp. None had evidence of overt multiple myeloma, of its variants, of primary systemic amyloidosis, or of other lymphoid tumors. In a patient with kappa type idiopathic BJP an elevation of a labelling index was found when an evolving myeloma developed 2 years later. The other had benign lambda type BJP until he died of bronchogenic carcinoma after 14 years. In most of patients with idiopathic BJP overt multiple myeloma or systemic amyloidosis have developed after a long period. An elevation of labelling index in the course of illness is expected to be a premonitory sign for malignant transformation. Idiopathic BJP may be characterized by less nephrotoxicity or amyloidogenicity of Bence Jones protein synthesized as well as a slow growth rate of tumor cells. PMID- 3107159 TI - [Hydroxyquinoline-induced interstitial pneumopathy]. PMID- 3107162 TI - Formation of polycystic ovary in mature rats by the long-term administration of human chorionic gonadotropin. AB - The critical role of high level of serum LH in polycystic ovary syndrome was evaluated in rats by the long-term administration of hCG. Wistar-Imamichi strain mature female rats (age; 12 weeks) which showed at least two consecutive estrous cycles in vaginal smears were daily injected 10 IU hCG subcutaneously from diestrus for 80 days. Control rats were received saline solutions. On the next day after the last administration the rats were killed, and serum hormone levels and histological changes in the ovaries were examined. In 8 of 11 control rats the vaginal smears showed the regular estrous cycles (group 1) during the experimental period. None of the controls exhibited polycystic ovaries. In 19 of 25 experimented rats there were old corpora lutea and degenerated follicles (group 2). The remained animals (n = 6; group 3) showed polycystic ovaries and no corpora lutea except one. HCG treatment elevated the serum prolactin and estradiol levels in group 3, but reduced the progesterone level. Thus, it was suggested that the hCG-induced formation of PCO in rats might be able to refer to the pathogenesis in polycystic ovary syndrome. PMID- 3107164 TI - Management of acid-base balance with red blood cell carbonic anhydrase (RCA). II. Control of acid-base balance with acetazolamide. AB - Acetazolamide, a carbonic anhydrase (CA) inhibitor, was used to normalize metabolic alkalemia. A dosage of acetazolamide for normalizing metabolic alkalemia has not yet been experimentally determined. The dosage of acetazolamide for this purpose is experimentally calculated in this paper. The correlation between various concentration of acetazolamide mixed with blood and the base excess (BE) levels in blood at the start of normalizing metabolic alkalosis was studied in vitro. The change rate of the BE level was calculated from BE levels noted before and after tonometry of the blood with and without acetazolamide. A dosage of acetazolamide which can cause the change rate of the BE level to decrease is considered to be an effective dosage. Metabolic alkalosis in vitro was produced by adding bicarbonate into the blood. An effective dosage of acetazolamide for metabolic alkalemia of which the BE range was from 0 to + 30 mEq/liter was calculated. CA activities in the kidney and the blood of dogs administered acetazolamide were examined. The effective dosage of acetazolamide obtained from in vitro experiments inhibited the CA activities not only in the blood but also in the kidneys. An effective dosage of acetazolamide to normalize a BE of + 10 mEq/liter in vitro was converted into about 7-12 mg/kg in vivo. This dosage inhibited the red blood cell carbonic anhydrase (RCA) activity to 20-40%, whereas the normal physiological variation range is 25%. An effective dosage of acetazolamide in the blood did not proportionally increase with an increase of HCO3- during severe alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107163 TI - Plasma GH responses to GHRH and other provocative stimuli in idiopathic GH deficiency with or without abnormal delivery. AB - Seventeen patients with idiopathic growth hormone deficiency (GHD) were divided into two groups: one has no perinatal abnormalities (group A, n = 7) and the other has perinatal abnormalities, i.e. breech delivery and asphyxia (group B, n = 10). To see whether there are any differences in hypothalamo-pituitary dysfunctions in the two groups, the pituitary growth hormone (GH) reserve was examined. After 100 micrograms of synthetic growth hormone releasing hormone (GHRH) injection, group A showed a much higher peak values compared to group B (mean +/- S.E.: 16.1 +/- 3.5 ng/ml vs. 3.6 +/- 0.7 ng/ml, p less than 0.01), although there were no differences in their baseline GH values. In addition, plasma GH responses to arginine and L-dopa, which were performed at the diagnosis of GHD, were also greater in group A than group B (mean peak value: arginine, 3.4 +/- 0.5 ng/ml vs 1.8 +/- 0.5 ng/ml, p less than 0.05; L-dopa, 3.2 +/- 0.7 ng/ml vs. 1.3 +/- 0.2 ng/ml, p less than 0.01). There were no significant differences in the bone ages in the two groups, but bone age to chronological age ratio and pubertal development were significantly lower in group B. High frequency of primipara was observed in group B (7/10) compared to group A (2/7). These results indicate that pituitary GH reserve is much impaired in GHD with abnormal delivery compared to that without abnormal delivery, probably depending on the irreversible hypothalamo-pituitary damages due to prolonged anoxic state during the delivery. Especially, such risks seems to be high when cases of breech presentation are delivered from primipara mothers. PMID- 3107165 TI - Inhibitory effect of L-methionine-deprived amino acid imbalance using total parenteral nutrition on growth of ascites hepatoma in rats. AB - The antitumor effect of an amino acid imbalance characterized by the absence of L methionine was investigated in AH-109A ascites hepatoma-bearing rats with the technique of total parenteral nutrition (TPN). A central venous catheter was placed at the superior vena cava of the rat and hypertonic glucose solution plus an amino acid mixture, an ordinary amino acid compound but lacking L-methionine and L-cysteine, was administered as protein source for seven days. Increases in the volume of ascites and the number of tumor cells were significantly inhibited in the rats receiving glucose plus L-methionine-free amino acid mixture compared to the control rats given glucose only, glucose plus ordinary amino acid mixture and laboratory rations. Unfavorable side effects of TPN with amino acid compound lacking L-methionine and L-cysteine were loss of body weight and development of hypoproteinemia. No evidence of hepatic injury and bone marrow suppression due to this treatment were obtained from the results of biochemical and hematological studies. In liver cells and ascites tumor cells, morphologically, prominent enlargement of the nucleoli was observed in the rats treated with the amino acid mixture lacking of L-methionine and L-cysteine. PMID- 3107166 TI - Chronic pulmonary effects in guinea pigs from prolonged inhalation of cotton dust. AB - Inhalation of cotton dust has been associated with development of byssinosis. An animal model has been described recently in which guinea pigs exposed to cotton dust for a 6-week period demonstrated acute respiratory reactions consisting of increased breathing frequency, reduced tidal volume, and airflow fluctuations most prominent on the first day of exposure following a period without exposure, often referred to as a "Monday" response (Ellakkani et al., 1984). The current study examined the effects of cotton dust inhalation for 52 weeks in order to evaluate the animal model for ability to demonstrate more chronic effects of cotton dust exposure. Twenty guinea pigs were exposed to 21 mg/m3 cotton dust for 6 hr/day, 5 days/week, for 52 weeks. Twenty control animals received sham exposure. Parameters used to indicate chronic effects included respiratory measurements, weight gain, lung volume and weight, and histopathological evaluation. Respiratory measurements were taken while animals were breathing ambient air and also while breathing a mixture of 10% CO2, 20% O2, and 70% N2. Pulmonary effects were noted to change during the 12 months of exposure. For the first 3 months experimental animals displayed an increase in breathing frequency and a decrease in breathing volume measured as whole-body plethysmographic pressure. These effects were pronounced on the "Monday" of each week. During Months 3-6, reactions occurred on each day of exposure, although Monday responses were most severe. After 6 months, respiratory reactions were pronounced daily. Other indications of a chronic effect of exposure were increased lung volume, measured by water displacement, 15.0 +/- 3.3 ml (mean +/- SD) for the exposed group, compared with 9.8 +/- 2.0 ml for the controls; increased lung weight 9.4 +/- 1.5 g vs 7.0 +/- 0.8 g; and bronchiolar epithelial hyperplasia and hyperplasia of alveolar type II cells. Additionally, a histomorphometric study of the lungs performed by others (Coulombe et al., 1986) detected changes in the peripheral conducting airways, including increased thickness of bronchiolar epithelium and increased thickness of septa at the alveolar level, denoting chronic exposure. Taken together, these results indicated chronic respiratory effects in guinea pigs as a result of 52 weeks of continued exposure to cotton dust. The parallel in development of symptoms in guinea pigs and in humans exposed to cotton dust indicates that the guinea pig is a suitable model for byssinosis. PMID- 3107167 TI - A time-course investigation of vitamin A levels and drug metabolizing enzyme activities in rats following a single treatment with prototypic polychlorinated biphenyls and DDT. AB - Xenobiotics previously characterized as selective inducers of drug-metabolizing enzymes were chosen to probe possible relationships between enzyme induction and vitamin A metabolism. Liver, kidney and serum retinol and retinyl palmitate levels were investigated in male Sprague--Dawley rats receiving a single i.p. injection of the polychlorinated biphenyls (PCBs), 2,2',5,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl or 2,2',4,4',5,5'-hexachlorobiphenyl (300 mumol/kg) or 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)-ethane (DDT) (150 mumol/kg). While 2,2',5,5'-tetrachlorobiphenyl, a weak or non-inducer, and 2,2',4,4',5,5' hexaclorobiphenyl and DDT, phenobarbital-type inducers of cytochrome P-450, led to no reduction in total vitamin A content of liver or kidney during the 7 day time-course, administration of 3,3',4,4'-tetrachlorobiphenyl, a toxic PCB and a potent 3-methylcholanthrene-type inducer of cytochrome P-450, resulted in progressively lowered liver vitamin A levels (to 40% of control values by day 7). During this time, kidney total vitamin A content increased 3-fold. The increase in kidney vitamin A (due primarily to increased retinol content) was only equal to 1/40 of total vitamin A which had disappeared from the liver. Although 3,3',4,4'-tetrachlorobiphenyl specifically induced certain drug-metabolizing enzyme activities, e.g. aryl hydrocarbon hydroxylase and UDP glucuronosyltransferase (toward 4-nitrophenol), no highly significant correlations were found among the vitamin A levels and drug-metabolizing enzyme activities in the liver (aminopyrine N-demethylase, aryl hydrocarbon hydroxylase, aldrin epoxidase, microsomal epoxide hydrolase, UDP-glucuronosyltransferase toward 4-nitrophenol, glutathione transferase toward 1-chloro-2,4-dinitrobenzene and cytochrome P-450 content) as determined by multiple linear regression analysis. PMID- 3107168 TI - Clinically significant danazol-carbamazepine interaction. AB - In six patients with epilepsy and fibrocystic breast disease the concentration in serum of antiepileptic drugs was obtained before, during, and after danazol therapy. Carbamazepine serum levels increased almost twofold in the presence of danazol. Thus, interaction between carbamazepine and danazol producing acute carbamazepine toxicity is clinically significant. If these drugs are administered concurrently, an awareness of the potential for this drug-drug interaction along with monitoring of carbamazepine levels is required for optimal patient care. PMID- 3107170 TI - Rejection of murine cardiac allografts. II. Evidence that splenocytes bearing Lyt2 inhibit responsiveness in long-term heart graft recipients. AB - Mixed lymphocyte culture--lymphocyte-mediated cytotoxicity (MLC-LMC) reactions by recipient spleen cells were strongly and specifically increased shortly after primarily vascularized heart grafts were placed in mice. Subsequently, in strain combinations in which eventual long-term graft survival occurred, the MLC-LMC became markedly suppressed, unlike the case in situations in which the recipients rejected their allografts. Unseparated spleen cells from long-term recipients are unchanged or slightly depressed in their in vitro MLC-LMC capacity. However, when splenocytes from the long-term B10.A recipients of B10.BR heart grafts were depleted of B cells and Lyt-2-positive cells, they were found to significantly enhance responses when added as third-party cells to MLC-LMC cultures. Similarly depleted splenocytes from naive mice were unaffected or depressed in their ability to contribute to this response as third-party cells. It was concluded that non-Ig-bearing, nonadherent Lyt 2+ lymphocytes from long-term heart graft recipient spleens were present that inhibited the responsiveness of other cells in these spleens. PMID- 3107169 TI - Long-term treatment with sodium valproate: monitoring of venous ammonia concentrations and adverse effects. AB - Adverse effects and venous blood ammonia concentrations were monitored over a period of 7 months in patients with epilepsy treated with valproate (VPA). During the 1st, 4th, 12th, 20th, and 28th weeks of therapy, blood samples for analysis of ammonia and anticonvulsants were taken immediately before the morning dose of VPA as well as 2 h after dosing. In all, 40 patients completed the follow-up; 16 of these (Group 1) received VPA alone, while the remaining 24 (Group 2) were treated simultaneously with VPA and other anticonvulsants (phenobarbital, phenytoin, and/or carbamazepine). In Group 1 patients, a slight though significant increase in ammonia concentrations was found during long-term VPA treatment; this trend was even more pronounced in Group 2 patients. The difference between postdose and predose ammonia levels in Group 2 patients was significant at each of the five follow-up examinations. In contrast, no such difference was demonstrated in patients of Group 1. VPA concentrations were found to be consistently higher in Group 2 patients than in Group 1. Twenty-three patients complained of various long-term adverse effects, while the other 17 remained symptom-free. The adverse effects reported included drowsiness, tremors, weight gain, hair loss, and gastrointestinal symptoms. Our data confirm the previously suggested hypothesis that changes in venous blood ammonia are particularly evident in patients taking VPA in combination with other antiepileptic drugs, such as phenobarbital and phenytoin. PMID- 3107171 TI - T cell function in chickens bursectomized at 60 hours of incubation. AB - Chickens surgically bursectomized in ovo (Bx) at 60 hr of embryonic development offer a unique model to study selectively the influence of the bursa of Fabricius on thymus-dependent immune functions because the lymphoid cells of these animals develop in the total absence of the bursal microenvironment. The Bx chickens have been shown to be unable to respond to antigenic stimulation by specific antibody production. In the present study, we have characterized different aspects of T cell-mediated immunity in Bx chickens. Our results indicate the existence of a normal, functional T cell system in these animals. Peripheral blood leukocytes from Bx chickens were able to induce normal graft-versus-host reaction and mixed lymphocyte reaction. The capacity of peripheral blood T cells from Bx animals to produce interleukin-2 was indistinguishable from that of their normal counterparts, suggesting normal function of T helper cells. We demonstrate that peripheral blood leukocytes from Bx birds have normal in vitro proliferative responses to nonspecific T cell mitogens, concanavalin A, and phytohemagglutinin, and to a specific antigen, keyhole limpet hemocyanin. The inability of the Bx chickens to respond to specific antigens is therefore restricted to B cells and to production of specific antibodies. Our findings indicate that the bursa of Fabricius is not necessary for the development of thymus-dependent immune functions and support the suggestion that the specific function of the bursa is the creation of antibody diversity. PMID- 3107172 TI - Lymphocyte subpopulations and memory of MHC antigens. I. Quantitative aspects of neonatal heart graft rejection in normal and immune rats. AB - Using PVG-RT1av1 neonatal heart grafts transplanted to the plantar space in irradiated PVG recipients, and adoptive transfer of normal and immune cells, we have analyzed the role of lymphocyte subsets in graft rejection. This assay was found to be reproducible and to show good dose-response characteristics, permitting a precise analysis of the potency of the cells transferred. Immune cells were 36 times more potent than normal cells and all of their activity was in the T cell fraction. The increase in potency of immune populations was entirely within the CD8+ population defined by the mouse monoclonal antibody MRC OX-8. The CD4+ population, defined by the antibody W3/25, in both normal and immune populations, restored first-set rejection. All the graft rejection activity of CD4+ cells could be ascribed to the MRC OX-22- subset of these cells. PMID- 3107173 TI - Prolongation of liver allograft survival induced by donor spleen cells in RT1 incompatible rats. PMID- 3107174 TI - Isolation and quantification of canine islet tissue for transplantation. PMID- 3107175 TI - Hepatitis-associated aplastic anemia after liver transplantation. PMID- 3107177 TI - The synergistic effect of cyclosporine and mizoribine on heterotopic heart and partial-lung transplantation in rats. PMID- 3107176 TI - Combined heart-lung transplantation in the rat. Comparison of thoracic and abdominal operation techniques. AB - Recently, we developed two techniques for the combined transplantation of heart and the left lung into the left hemithorax of rats. One technique, with two vessel anastomoses, comprised the microsurgical repair of aorta, anterior vena cava, and left main bronchus. With the other, single vessel technique, only the aorta and bronchus were anastomosed. In this study, we determined the function and histology of syngeneic and cyclosporine (CsA)-treated allogeneic grafts transplanted with both techniques, and compared the results with those of heterotopic heart-lung grafts transplanted with a previously described technique for transplantation into the rat's abdomen. The survival rate of rats operated with either of the thoracic transplantation techniques was high (83%). Lungs and hearts of the grafts functioned well for over two months and had normal morphology when the double vessel technique was used. With the single vessel technique, the function of the lungs started to deteriorate from the third postoperative week onward, probably secondary to congestion. The results of thoracic grafts were superior to those of abdominal transplants, where the nonventilated lungs--especially during immunosuppression--were frequently infected. We conclude that these new techniques for thoracic transplantation are most suitable for research of combined heart-lung transplantation. PMID- 3107178 TI - Hamster-to-rat orthotopic liver xenografts. PMID- 3107179 TI - Prolonged survival of intraportal versus subrenal capsular transplanted islet allografts. PMID- 3107180 TI - [Possibility of the long-term fixation of the cells of a HeLa culture without disturbing their ultrastructure]. AB - It is shown that the composition of fixatives (2.5% glutaraldehyde in 0.1 M phosphate buffer with pH 7.2-7.4, and the mixture of 2.5% glutaraldehyde with 2% paraformaldehyde in 0.1 M phosphate buffer with pH 7.2-74) and duration of fixation (30 minutes, 24 hours, 7 days, and 30 days) under the room temperature exerts no influence on preservation of HeLa cultured cells. The ultrastructure of all the organelles of these cells is similar in any cases examined. All the membrane structures are well preserved; no condensation of chromatin is observed; the widths of the canals of endoplasmic reticulum, and of the intracristal and lateral spaces of mitochondria are invariable. Polysomes are present in the cytoplasm throughout the period of fixation. PMID- 3107181 TI - Preoperative chemotherapy and radiotherapy in the management of epidermoid carcinoma of the anal canal. AB - Sixteen patients affected by epidermoid carcinoma of the anal canal were treated preoperatively by means of an i.v. infusion of mitomycin C (15 mg/m2) on day 1 and 5-fluorouracil (750 mg/m2) days 1 to 5, followed by radiotherapy (3000 R in 3 weeks). Four to 6 weeks after the end of radiotherapy the response to the preoperative treatment was evaluated by means of biopsy. A reduction of the neoplastic mass was observed in 13 of the 16 patients. An evident correlation exists between the stage of the tumor and 1) the response to preoperative treatment, 2) local recurrence, and 3) long-term survival. In fact: 3/4 T1 patients reached a complete response (CR), and 1/4 T1, 5/5 T2 and 4/7 T3 patients achieved a partial response (PR); only 3/7 T3 patients never responded to preoperative treatment. After the initial surgery, only T2 (3/5) and T3 (4/7) patients underwent a second operation for a recurrence. Overall survival at 42 months was 62.5% (T1, 100%; T2, 80%; T3, 28.5%). PMID- 3107182 TI - [Neutropenia during treatment with valproate]. PMID- 3107183 TI - [Self-administered intermittent enteral nutrition. A therapeutic method in chronic malnutrition]. PMID- 3107184 TI - [Scavenging of excess gas from a pediatric nozzle insufflation system]. PMID- 3107185 TI - [Perforated duodenal diverticulum]. PMID- 3107186 TI - [Rhabdomyolysis with acute renal failure after a grand mal seizure]. PMID- 3107187 TI - [Flecainide. A new anti-arrhythmic agent]. PMID- 3107188 TI - [Prostaglandin E1 (misoprostol) versus cimetidine in the treatment of duodenal ulcer. A controlled clinical trial]. PMID- 3107189 TI - Blood-gas transport in awake rabbits exposed to normobaric hyperoxia. AB - The time course and terminal effects of normobaric oxygen exposure on the gas transport chain were studied in awake, catheterized rabbits exposed to air (n = 8) for 96 h or 100% O2 (n = 10) until death. O2-breathing animals survived 60.2 (+/- 13.5 SD) h. Pao2 increased and was maintained until within 4.9 (+/- 1.4) h of death. Mixed venous O2 tension rose sharply but transiently upon O2 exposure. In most animals, death followed a precipitous fall in PaCO2, a moderate rise in PaCO2, and a drop in pHa. The terminal acidosis was largely metabolic, nearly half due to lactic acidemia. There were transient appearances of metabolic acids early in the exposures before the PaCO2 decreased. Furthermore, in the last hours, fixed acids appeared when PaCO2 was unchanged or slightly decreased, but before the animal became hypoxemic. Metabolic acidosis without arterial hypoxemia could result from cardiac insufficiency, or alterations in metabolism, or in patterns of distribution of blood flow within peripheral beds. Thus, normobaric O2 exposure has precipitous and terminal effects on pulmonary gas exchange, but arterial hypoxemia is not necessarily the cause of death. PMID- 3107190 TI - [Pulmonary fibrosis following instillation of mitomycin C in the urinary bladder]. AB - Intravesical prophylaxis against recurrence of bladder carcinomas using mitomycin C has proved to be an effective treatment with few side effects. No side effects involving the lungs have so far been observed with systemic administration; with intravesical use, however, this is not the case. We report a 32-year-old man in whom pulmonary interstitial fibrosis occurred after intravesical instillation of mitomycin C. The clinical picture, including the therapy, and the differential diagnosis and practical consequences are all discussed. PMID- 3107191 TI - The best suture for hypospadias? AB - In a study designed to determine the best suture for use in hypospadias surgery, polydioxanone (PDS), chromic catgut, and polyglycolic acid (Dexon) were studied under similar conditions in the penile foreskin of 16 baboons. Gross and microscopic observations were made at intervals of six to forty-eight days. The wounds sutured with catgut were all healed by twenty-four days with complete suture resorption and no evidence of scar formation. Both polyglycolic acid and polydioxanone sutures showed delayed resorption, wound abscesses, and granulomas. Catgut remains the best available suture to use in the penile foreskin. Polyglycolic acid and polydioxanone sutures, because of their prolonged resorption and excess reaction, should not be used in hypospadias surgery. PMID- 3107192 TI - Urethral diverticulum in females. PMID- 3107193 TI - Surgical diseases of the esophagus. AB - The diagnosis and management of surgical diseases of the esophagus are discussed. Esophageal foreign bodies, strictures, esophagobronchial fistulas, diverticula, gastroesophageal intussusception, hiatal hernias, and megaesophagus are included in the discussion. PMID- 3107194 TI - [Interdependence of the level of total proteins, magnesium and beta-carotene in the plasma of dairy cows]. AB - The degree of dependence of the concentration of total protein, magnesium and beta-carotene in the blood plasma of over 3,400 dairy cows in the first and second phases of lactation and in months 8 and 9-9.5 of pregnancy was attested statistically. It was shown that in late pregnancy the concentration of all three indices drops both with winter and summer feed rations and that the connection between all three pairs of indices is positive. The highest values of the linear correlation coefficient were ascertained between the total protein and magnesium of blood plasma (+0.87 in the winter period, +0.63 in the summer period and +0.75 in both periods), the correlation was somewhat lower between magnesium and beta carotene (+0.56, +0.75 and +0.36) and it was lowest between total protein and beta-carotene (+0.45, +0.41 and +0.42). The discussion deals with the causes of the stochastic correlation of these components of blood plasma. PMID- 3107195 TI - [Changes in the acid-base equilibrium in cattle in relation to the time intervals between sampling and study under field conditions]. AB - The parameters of acid-base balance were investigated in relation to the time difference between the blood sampling and the examination and ambient temperature in the field conditions. The transfer of the samples from field conditions to a laboratory was imitated by putting the case with the samples into a thermostat at the temperature of 20 degrees C and 37 degrees C. In the first trial, at the temperature of 20 degrees C, statistically significant changes in pH values were recorded in seven hours. If the temperature in the case was 37 degrees C, the differences in pH, BE, SBi and BB values and in the partial pressure of CO2 were statistically significant in six hours. Applying the above results we state that the acid-base parameters can be examined within five hours after blood sampling supposing that the blood samples are kept at the temperature of 0-4 degrees C and using for veterinary diagnostics the equilibration method after Astrup. PMID- 3107196 TI - [Incidence of the 1/29 Robertsonian translocation in the cattle population in Czechoslovakia]. AB - We studied the inheritance of a serious chromosomal aberration--Robertsonian translocation 1/29 (R.t.1/29) in the female and male progeny of three successive generations after five heterozygous sires, carriers of this chromosomal aberration. Of the total number of 43 progenies that were examined cytogenetically, we found in ten sons of the second successive generation R.t.1/29 in 50% and in 26 daughters in 53%. In the third successive generation we found out this chromosomal aberration in one of two bullocks and in none of five heifers. In all cases we recorded the diploid chromosome number 59,XYt or 59,XXt in heterozygous constitution, in 100% of all examined mitoses. The translocation is of a monocentric type. The results including the data on the fertility of sires do not, however, demonstrate explicitly the reduced fertility of sires with this aberration, or of their progeny, as mentioned by some researchers. PMID- 3107197 TI - [Ultrastructure of frozen and thawed ram sperm]. AB - With the aid of a transmission electron microscope we studied the ultrastructure of frozen and thawed ram sperm. The cryoprotective agents do not completely prevent the occurrence of structural changes in spermatozoa. The sperm membrane system is affected. The greatest and most frequent damage is to the acrosome, the cell membrane and mitochondria are less injured. We observed regional differences in the damage to the cell membrane. It is most damaged above the acrosome, least in the postacrosomal area and in the principal piece of the tail. We found considerable variability in the changes among individual spermatozoa from the same ejaculate. The changes are not in the nature of mechanical damage as a result of the occurrence of ice microcrystals. We therefore think that the occurrence of structural changes is dependent on damage at molecular level and consists of a change in the physical-chemical properties of membranes. PMID- 3107198 TI - [Correlation between the acid-base equilibrium of blood as determined on the ABL4 Astrup apparatus and possibilities of studying blood after storage]. AB - With the latest type of Astrup machine ABL4 we studied the temporal dynamics of blood-testing immediately following the taking of the blood-sample and then after 30 minutes, 3, 6 and 8 hours. After suitable storage of the samples (in a refrigerator at a temperature of +5 degrees C) we did not record any statistically significant differences in the values of the acid-base indices of blood after any interval of time. After testing the Radiometer hypodermic syringe, which the manufacturer supplies for the taking of arterial blood-samples from humans, it was shown that it was also completely suitable for taking venous blood-samples from animals. After application of a glass bead and mixing, the blood did not congeal even after eight hours. Testing both Radiometer and Rekord syringes for the taking of blood-samples, we ascertained that the results pointed to the suitability of both in ascertaining the acid-base values in all the intervals of time studied by us. PMID- 3107199 TI - [Horse infestation with the larva of the deer warble fly, Hypoderma diana Brauer, 1985 (Diptera, Hypodermatidae)]. AB - In South Bohemia a case was discovered of a yearling colt attacked by the larva of the IIIrd instar of the deer warble fly Hypoderma diana Brauer. The dead, almost mature larva of the fly was squeezed out of a subcutaneous lump above the shoulder in the first decade of April, 1985. The case is evaluated from the point of view of the possibility of the transition of specific parasites--warble flies- to another host. The attacking of a non-specific kind can occasionally occur only when there is a large number of the parasites and both kinds of host. At present the degree of attacking of deer by subcutaneous warble flies is high and therefore under favourable circumstances even domestic animals can be attacked by this type of warble fly. The above case is the first to be ascertained of a horse being attacked by a deer warble fly. PMID- 3107201 TI - Occurrence of Listeria monocytogenes in raw milk. PMID- 3107200 TI - Experimental encephalitozoonosis in neonatal dogs. AB - The in vivo infection of neonatal dogs by the microsporidian protozoan parasite, Encephalitozoon cuniculi, was studied. Microscopic examination of tissues from infected animals showed granulomatous nephritis, meningoencephalitis, hepatitis, and pneumonitis. A large component of the inflammatory infiltrate consisted of plasma cells and lymphocytes. In addition, hyperplasia of B-lymphocyte-dependent regions of lymph nodes and erythrophagocytosis were consistently seen in infected dogs. Infected dogs developed lymphocytosis, hypergammaglobulinemia, anti encephalitozoon antibodies, and an antigen-specific blastogenic response to E. cuniculi spores. Lymphocyte blastogenic responses to the lectin phytohemagglutinin A (PHA) were depressed compared to controls. Dogs dying during the 2-month experimental trial were bacteremic. The findings of these experiments suggest that postnatal infection results in a demonstrable although seemingly ineffective immune and inflammatory response without detectable clinical disease. PMID- 3107202 TI - Bilateral facial paralysis in a cow with listeriosis. PMID- 3107203 TI - Further evidence supporting the concurrent influence of aflatoxin and manganese. AB - Trace elements, including manganese may afford protection from deleterious effects of aflatoxin. Young male Fischer rats received ip injections of aflatoxin B1 (AFB1) in dimethyl sulfoxide (DMSO), 1 mg/kg, 2 mg/kg or 4 mg/kg. Control groups received DMSO ip or no injection. All animals were intubated with 3 microCi of [54Mn]-MnCl2 12 hr post-injection. Sacrifice occurred 72 hr after gavage of the radiolabel. All tested levels of AFB1 affected the loss of total body radioactivity. This response was observed within 12 hr when toxin-treated groups excreted almost 4 times more counts than controls. From 12-36 hr following radiolabel administration, AFB1 appeared to enhance excretion; by 72 hr, toxin treated animals (especially those receiving higher doses) appeared to conserve the metal. Aflatoxicosis manifested itself through reduced body weight gain. The data provide support evidence that Mn and AFB1 biointeract. PMID- 3107204 TI - A rapid analysis of water for anatoxin a, the unstable toxic alkaloid from Anabaena flos-aquae, the stable non-toxic alkaloids left after bioreduction and a related amine which may be nature's precursor to anatoxin a. AB - Poisoning of animals by Anabaena Flos-Aquae alkaloid is a common, but sporadic event (1). Anatoxin A is the toxic principle responsible for acute fatalities (2), and tends to disappear along with the toxicity within a few days of the event, thus complicating diagnosis. This report reveals our simplified analytical methodology for Anatoxin A (2-acetyl-9-azabicyclo[4.2.1] non-2,3-ene), for the non-toxic compounds into which it bioreduces, the chair and boat forms of 2 acetyl-9-azabicyclo[4.2.1] nonane, and for an as yet uncharacterized amine C10H15N. PMID- 3107205 TI - Effect of PCB on some MFO enzyme activities in pregnant and virgin rabbits. AB - Fenclor 64 (a PCB's commercial mixture) was administered twice i.p. to virgin and pregnant New Zealand rabbits at the dose of 100 mg/Kg to evaluate its inducing properties on the following hepatic microsomal MFO activities: p-nitro-anisole-O demethylase, amino-pyrine-N-demethylase, acetanilide-hydroxylase and aryl hydrocarbons-hydroxylase. The results indicate that Fenclor 64 evoked a "mixed type" induction in virgin as well as in pregnant rabbits since it increased liver weight, cytochrome P-450 levels, as well as p-nitro-anisole-O-demethylase and acetanilide-hydroxylase. Pregnancy by itself affects only amino-pyrine-N demethylase levels. PMID- 3107206 TI - Left ventricular ultrastructure in pulmonary stenosis and in tetralogy of Fallot. AB - Twelve patients underwent haemodynamic studies and myocardial biopsies: 7 with pulmonary stenosis (PS) and 5 with tetralogy of Fallot (TOF). Their ages ranged between 2 and 43 years. Right ventricular pressure was 128 +/- 43 mmHg in PS and 98 +/- 8 mmHg in TOF. Aortic blood oxygen saturation was 97.0% +/- 1.4% in PS, and 88.4% +/- 6.3% in TOF. Left ventricular (LV) weight was normal in TOF while it was increased in PS: 140.7 +/- 74.3 vs 74.0 +/- 8.7 g/m2 (P less than 0.001). Contractility was altered in both PS and TOF: ejection fractions were 56% +/- 7% vs 65% +/- 6% (P less than 0.001). Light microscopy showed abnormal transverse diameter of left ventricular myocytes in both PS and TOF: 18.6 micron +/- 4.0 micron vs 19.4 micron +/- 4.9 micron. The percentage of interstitium was normal: 29.6% +/- 3.9% vs 26.2 +/- 5.1%. Transmission electron microscopic examination revealed hypertrophic changes in all patients and degeneration in 7 of them. Hyperfunctional alterations of the myocytes were characterized by the increased number and reduced size of mitochondria, the enlarged Golgi complex, the increased number of ribosomes, the marked folding and convolutions of the nuclear membrane, the dilatation and tortuosity of T tubules. Myofibrillar lysis was the major degenerative change, which was also observed in the right ventricle (RV) of the same patients. No correlation was observed between these alterations and the patient ages, RV pressures, aortic blood oxygen saturations and ejection fractions. These findings led us to conclude that: (1) suprasystemic pressure overload of the RV induces macroscopic LV hypertrophy; (2) mild and suprasystemic pressure overload of the RV induces hyperfunctional changes in the LV; (3) myocardial degeneration is not related to hypertrophy nor to hypoxia, but is part of a more widespread cardiovascular fetopathy. PMID- 3107207 TI - The host-parasite relationship of Toxoplasma gondii in the brains of chronically infected mice. AB - The host parasite relationship in the brains of asymptomatic mice chronically infected with Toxoplasma gondii was examined at 3, 6 and 12 months post-infection (PI) using electron microscopy. The parasites were located in large numbers within tissue cysts which ranged in size from 10-50 microns in diameter. The cysts were predominantly found in the grey matter. The toxoplasms were enclosed by a cyst wall consisting of a membrane, with irregular invaginations, and an underlying layer of homogeneous osmiophilic material. A detailed examination of 50 cysts revealed that all the cysts were present within intact host cells irrespective of their size or the period PI. The majority of host cells could be positively identified as neurons by the presence of synapses. No extracellular cysts were observed. It is probable that the intracellular location of the cysts protects them from recognition and attack by the host immune system. PMID- 3107208 TI - Ultrastructural alterations in cardiac muscle of diabetic BB Wistar rats. AB - The cardiac muscle of BB Wistar rats suffering from diabetes for 8 and 16 weeks (8-Wk and 16-Wk of DM) were examined by light and electron microscopy. The diabetic rats were kept alive by injections of small doses of insulin and exhibited severe hyperglycaemia, glycosuria and weight loss. The heart/body weight ratio of all diabetic groups was greater than that of age matched controls. Over the experimental period, the left ventricular myocardium of the diabetic BB rats sustained damage that was progressively more serious with the duration of the diabetic state. In BB rats after 8-wk of diabetes the myocardium contained large numbers of lipid droplets and glycogen granules around mitochondria which showed patchy swelling, and slight loss of myofilaments. Disruption of mitochondrial membranes and extensive loss of myofilaments were seen in rats diabetic for 16 wk. In addition, dilatation of the sarcoplasmic reticulum-transverse tubular system, formation of a contraction band and myelin bodies and widening of the intercellular space at the fasciae adherens of the intercalated disc were characteristically observed in BB rats after 16-wk of diabetes. However, there were no evident alterations in the capillaries of any diabetic BB rats. Morphometric analyses showed the volume percentage of myofibrils in diabetic rats to be significantly decreased when compared with controls. The loss of myofibrillar elements may be a primary damage induced by insulin deficiency. The formation of contraction bands suggests Ca2+ overload caused by diabetic metabolic disturbances. PMID- 3107210 TI - Malignant teratoma of the left colon associated with chronic ulcerative colitis. AB - An autopsy case of a malignant teratoma of the descending colon is presented, the first observed in this site. A 41-year-old woman had suffered from chronic ulcerative colitis and was operated because of an abscess forming a mass in the left colon. However, the tumour proved to be inoperable and the patient died from septicaemia. Histologically, the tumour was a highly metastasizing malignant teratoma containing mature tissue elements (hair, cartilage, adipose tissue, squamous epithelium, bronchial, endometrial and cervical tissues). The relationship between the ulcerative colitis and the teratoma is obscure. PMID- 3107209 TI - Synaptophysin: a reliable marker for medulloblastomas. AB - Synaptophysin is an acidic, integral membrane glycoprotein (Mr 38,000) of presynaptic vesicles in various neurons and neuroendocrine cells, and in tumours derived from such cells. By indirect immunofluorescence microscopy of cryostat sections, using the monoclonal antibody SY 38 to synaptophysin, a consistent positive immunoreactivity was observed in all medulloblastomas (n = 6) and neuroblastomas (n = 3) as well as a ganglioneuroma and a glioneuronal hamartoma. The presence of synaptophysin in medulloblastomas was confirmed biochemically by immunoblotting experiments. For purpose of comparison, the expression of intermediate-sized filament (IF) proteins was also examined. While neurofilament proteins were consistently expressed in the neuroblastomas (3/3), the ganglioneuroma and the glioneuronal hamartoma, IF distribution in medulloblastomas was variable. A neurofilament-positive type of tumour (1/6) could be distinguished from vimentin-expressing neoplasms (4/6) by immunocytochemistry. These data indicate that synaptophysin is a reliable marker for medulloblastomas as well as other differentiated and undifferentiated neuronal tumours and in this respect is superior to the more heterogeneous expression patterns of IF proteins in these tumours. PMID- 3107211 TI - Immunohistochemical demonstration of glial markers in retinoblastomas. AB - Twenty retinoblastomas were studied immunohistochemically in order to visualize glial cells. In the retina, the glial cells in the ganglion cell layer and the Muller cells were GFAP positive, while only the glial cells of the ganglion cell layer expressed S-100 reactivity. In the tumours S-100/GFAP positive glial cells were found in areas near the retina and along many tumour vessels. Some S-100 reactive cells previously interpreted as tumour cells were refound in a few tumours. In areas with Flexner-Winterstein rosettes and in areas with light cells showing photoreceptor-like differentiation, glial cells reactive for both S-100 and GFAP were demonstrated. The latter findings may represent differentiation in a glial direction in the more mature parts of retinoblastoma. PMID- 3107212 TI - The fine structure of gliomatosis cerebri. AB - The ultrastructural features of five biopsies of gliomatosis cerebri (GC) are described. Four main types of tumour cells are seen: anaplastic astrocytes poor in organelles with a variable amount of glial microfilaments; atypical oligodendrocytes with scanty cytoplasm in which microtubules are present; intermediate forms with aboundant cytoplasm rich in organelles, with microtubules and microfilaments; and small cells with round nuclei and a very scanty rim of cytoplasm. In two cases several concentrically folded cytoplasmic lamellae of glial processes were arranged either around themselves or around the perikaryon of other cells. This ultrastructural study indicates that GC is a neoplastic process of small undifferentiated elements, transitional forms of astroglia (to oligodendroglia) and anaplastic cells of astrocytic origin in all stages of development. PMID- 3107213 TI - The antral gastrin-producing cells in duodenal ulcer patients. A light microscopic and ultrastructural study during long-term, low dose treatment with cimetidine. AB - The antral mucosa has been examined in four duodenal ulcer patients before and during long-term, low dose treatment with cimetidine (given a total dose of between 472 g and 894 g). No convincing changes were found in the number or the volume of G cells. Signs of inactivity were demonstrated ultrastructurally, with small granules of intermediate type, a reduced amount of granular endoplasmatic reticulum and Golgi complex, mostly showing no signs of granulogenesis. The occurrence of bundles of cytoplasmic microfilaments, not observed before treatment and the reduced number of D cells may also be signs of inactivity. Hyperplasia and/or neoplasia were not seen in other antral endocrine cells. PMID- 3107214 TI - Human immunodeficiency virus infection of monocytic and T-lymphocytic cells: receptor modulation and differentiation induced by phorbol ester. AB - The monocytic leukemic cell line U937 can be infected with human immunodeficiency virus type 1 (HIV-1) to become permanently infected virus producers. Uninfected U937 cells express T4 (CD4) antigen and form syncytia when mixed with HIV-1 producing cells. Anti-T4 monoclonal antibodies block syncytium formation indicating that the HIV-1 receptors on U937 cells include T4 antigen. The promyelocytic leukemic cell line HL60, while expressing only low amounts of surface T4 and not forming syncytia on exposure to HIV-1, can be infected by HIV 1 at lower efficiency than U937 and T-cell lines. 12-O-Tetradecanoylphorbol-13 acetate (TPA) treatment induces the differentiation of U937 cells into macrophages. HIV-infected U937 cells retain the ability to differentiate, though less efficiently, as shown by the appearance of monocyte/macrophage surface markers. T4 antigen on both U937 and T-cell lines is down regulated by TPA treatment. Functional receptors for HIV-1, assayed by syncytium induction and pseudotype plating, are lost concomitantly with T4 antigen following TPA treatment of U937 cells and T cells. PMID- 3107215 TI - [Effect of decimeter-wave therapy and "dry" carbon dioxide baths on the regional hemodynamics of patients with atherosclerosis of the aorta and peripheral vessels in the early postoperative period]. PMID- 3107217 TI - [Selection phage-resistant strains of Bacillus subtilis for alpha-amylase production]. PMID- 3107216 TI - [Effect of acid extraction on the osteogenic activity of bone tissue]. AB - Rat bones demineralized in HCl and TCA exhibited distinct osteoinductive activity while the bones demineralized using EDTA did not show the activity. HCl- and TCA extracts of bones differed from EDTA extracts by chromatographic and radiochromatographic profiles. At the same time, HCl- and TCA-extracts contained additional fraction. The substances involved in the fraction appear to be responsible for inhibition of the osteoinductive factor of bone tissue. PMID- 3107218 TI - [The effect of nucleic acids and their precursors on the growth of Mycobacterium tuberculosis H37Ra and BCG]. PMID- 3107219 TI - Cost-effectiveness of fecal occult blood screening. PMID- 3107220 TI - Technology for water supply and sanitation in developing countries. Report of a WHO Study Group. PMID- 3107221 TI - Hospitals and health for all. Report of the WHO Expert Committee on the Role of Hospitals at the First Referral Level. PMID- 3107222 TI - Acceptability of cell substrates for production of biologicals. Report of a WHO Study Group on Biologicals. PMID- 3107223 TI - Pharmacological significance of the species differences in bupropion metabolism. AB - Bupropion provided a dose-dependent prevention of tetrabenazine-induced sedation in mice but not rats. Bupropion was extensively metabolized in mice, rats, dogs and man. About 85% of the dose was excreted in urine of rats and man. The predominant metabolites in rat urine were side chain cleavage products of bupropion (m-chlorobenzoic acid) with a minor fraction consisting of basic side chain hydroxylated metabolites. Mice, dogs and man form a major side chain hydroxylated product (BW 306U) which appeared in higher concentration than bupropion in plasma of these species but not rats. The relatively high plasma levels of BW 306U in mice but not rats may account for the species difference in pharmacological response observed with bupropion. PMID- 3107224 TI - Potential mechanisms for redistribution of polychlorinated biphenyls during pregnancy and lactation. AB - Female mice treated with 14C-2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) two weeks prior to mating eliminated virtually their entire body burden of the compound through milk during one lactation cycle. 6-CB was shown to distribute among rat and human plasma lipoproteins and protein in vitro. It was readily transferred among plasma constituents and its distribution was related to the triacylglycerol:protein ratio in plasma. At one hour following its intravenous administration to virgin rats, 6-CB was primarily distributed to LDL. With the hypertriglyceridemia of late pregnancy, more than 70% of circulating 6-CB was associated with VLDL. VLDL is a major substrate for mammary gland lipoprotein lipase which is elevated during lactation. When 6-CB was complexed with human VLDL and injected i.v. into late pregnant mice, mammary gland concentrations of 6 CB exceeded those of adipose tissue at all sacrifice times between 5 min and 6 h. No differences between adipose tissue and mammary gland concentrations of 6-CB were observed with Emulphor:ethanol:saline as vehicle until 6 h. Isolated hepatocytes were capable of secreting protein and triacylglycerol in the form of VLDL into serum-free media. Eighty percent of 6-CB released from hepatocytes was in association with VLDL, with the remainder in association with protein. Adipocytes isolated from epididymal fat pads of male rats which were pretreated with 6-CB released progressively less radioactivity to incubation media with time after treatment even though PCB content of these cells increased. 6-CB may not be evenly distributed among adipocyte lipids. PMID- 3107225 TI - Transdermal drug delivery and cutaneous metabolism. AB - The delivery of drugs via the skin to achieve systemic therapeutic effect is currently under intense investigation. The skin offers unique advantages and limitations for drug input into the body. For example, while hepatic first pass may be circumvented, the excellent barrier function of the stratum corneum (the thin outermost layer of skin) precludes, at present, all but the most potent drugs from this route of administration. Examples of approved transdermally delivered drugs are scopolamine, nitroglycerin, clonidine and estradiol. The delivery systems which have been formulated for these agents have been designed to provide essentially zero-order input kinetics for between 1 and 7 days. The impact of cutaneous metabolism on transdermal drug delivery has not yet been evaluated rigorously. Limited in vivo data for nitroglycerin suggest a cutaneous first pass effect of between 10 and 20%. More work has been directed towards the use of topical prodrugs and the design of molecules better able to transport across the stratum corneum and then undergo local enzymatic activation. Further research in this area will require a more specific quantitative understanding of the metabolic capabilities of human skin in vivo. PMID- 3107226 TI - [Complications of parenteral nutrition]. PMID- 3107227 TI - Long term home oxygen therapy in chronic respiratory care--a Belgian experience in management. AB - Report on organization, financing, indications, preceding examinations, current observation, practical experiences and results during 2 years of application of oxygen concentrators in long term home treatment of patients with chronic respiratory distress. The authors plead for less restricted indications and propose measures to extend the action area of the patients. PMID- 3107228 TI - [Infections caused by Mycoplasma pneumoniae in children and adolescents]. AB - The authors describe the signs and symptoms in 82 children and adolescents with infections due to Mycoplasma pneumoniae, diagnosed by the complement fixation reaction. They discuss the results in relation to other reports about mycoplasma infections. PMID- 3107229 TI - [Nutritional status and small intestine absorption]. AB - A high percentage of hospitalized patients are malnourished. By means of biochemical examinations (visceral proteins), anthropometric measurements (body mass, triceps skinfold, arm muscle circumference, creatinine index) and immunological methods (total lymphocyte count in the blood, skin testing with test antigens) it is possible to classify nutritional conditions in severity and kind of malnutrition. 158 patients with chronic inflammatory diseases of the GI tract and cancer without generalization were studied by means of an exact nutritional assessment and by means of the modified D-xylose test. There was no significant correlation between the degree of malnutrition and the extent of intestinal absorption. Only in 5.7 per cent of malnourished patients existed a malabsorption. PMID- 3107230 TI - [Studies of protein clearance in patients treated with and without gold preparations in rheumatoid arthritis]. AB - It is reported on investigations of protein clearance in rheumatics treated with Tauredon in comparison to non-treated patients suffering from rheumatoid arthritis. In that way no significant differences concerning the secretion of selective and unselective proteins could be found between the observed groups of patients. Secondary effects of the gold therapy in the form of a relevant proteinuria as elaborated by some authors cannot be confirmed in our patients. On the other hand investigations of protein clearance allow the premature recognition of renal failure and thus they can contribute to the increasing of the patients' security in the application of this therapy. PMID- 3107231 TI - [Recent aspects of Parkinson therapy]. AB - After a short summary of the leading symptoms, the neuropathological and the pathobiochemical findings in Parkinson's disease, the possibilities of pharmacological treatment are pointed out. The choice of the suitable medication depends on the stage and severity of the disorder and the leading symptoms. Medical side-effects and contraindications of the different antiparkinsonica must be considered. Problems of long-term medication especially of L-dopa are discussed. Examples of reasonable "combined therapies" are given allowing the attempt to reduce the L-dopa dose without losing treatment effectiveness. In addition to the pharmacological treatment and for special indications, surgical i.e. stereotactic manipulations, intensive physiosocial care, physiotherapy and logotherapy are very necessary. PMID- 3107232 TI - [Long-term dialysis treatment in advanced age]. AB - In Europe 40% of patients under regular dialysis therapy (RDT) are aged over 55. In our hospital 40% of patients under RDT are aged over 70%. The causes of terminal renal failure in the aged are similar to those of the younger patients. 45% of patients between 60 and 70 years and 25% of those between 70 and 80 years survive 5 years after initiation of RDT. Quality of life under RDT is good enough for the elderly to be grateful for prolongation of their lives. A general upper age limit for RDT is difficult to set. In rare instances RDT may become questionable in the aged, mainly when cerebral dysfunction becomes prominent. In these cases it might be ethical not to start, or to withdraw from RDT. PMID- 3107233 TI - An integrated molecular and immunological approach towards a meningococcal group B vaccine. AB - There has been a notable lack of success in producing an effective vaccine against Neisseria meningitidis group B infections, despite such prophylaxis being available for group A and C disease. The reasons for this are reviewed and evidence presented that a vaccine based on the group B capsular polysaccharide should be pursued. To be effective, a clear understanding of, and improvement in the poor immunogenicity of the polysaccharide is required. Consequently, the nature of the antigenic structure involved in immune recognition has been evaluated at the molecular level and reasons for the poor immunogenicity of the B polysaccharide are presented. Methods of increasing the immunogenicity are proposed with the intention of undertaking human volunteer trials. PMID- 3107234 TI - Prospects for the prevention of meningococcal disease: special reference to group B. AB - Safe and effective polysaccharide (PS) vaccines for prevention of bacteraemia and meningitis due to meningococcal serogroups A, C, Y, and W135 have been licensed for a number of years in the United States and in some European countries. The bivalent AC and the tetravalent ACYW135 PS vaccines have generally been used in the civilian population only for the control of outbreaks. A major meningococcal disease problem persists in parts of Africa, especially in the so-called 'meningitis belt'. Studies by Greenwood and Wali have shown that a cost effective way to control the disease in Africa is to vaccinate the entire population of a village at the start of an outbreak. When this was done they found that further cases of group A disease ceased within ten days. There are, however, some problems with the existing PS vaccines. The group C PS is less immunogenic in young children than the three other PS, and does not protect children below 18 to 24 months of age. This problem will probably be solved by conjugation of the group C PS to a protein carrier, analogous to that which has been done with the Haemophilus influenzae type b PS. PMID- 3107235 TI - [A case of juvenile xanthogranuloma]. PMID- 3107236 TI - [Effect of isorhythmic and heterorhythmic stimulation of the septum and mammillary bodies on the EEG of the rabbit]. AB - The influence was studied of combined isorhythmic and heterorhythmic stimulations of the septum and mammillar bodies (S + MB) on spatial organization of brain biopotentials and on the speed of acquisition of defensive conditioned reflex (CR) to light. Analysis of the effect of the isorhythmic stimulation on learning showed that CR elaboration was impeded and in some situations was even impossible. Apparently, isorhythmic S + MB stimulation did not prevent closing of the temporary connection but disturbed CR realization. At simultaneous heterorhythmic electric S + MB stimulations, in most cases cortical parts reproduced only one rhythmic process corresponding to the frequency of the septal stimulation. Combined heterorhythmic S + MB stimulation promoted successful defensive CR elaboration though prolonged action of such stimulations led to development of neurotic state in animals. PMID- 3107237 TI - [Effects of injecting 6-hydroxydopamine into areas of the nigro-striatal (A9) and mesolimbic (A10) dopaminergic systems on the elaboration of a conditioned feeding reflex in the rat]. AB - Wistar male rats were bilaterally injected under nembutal anaesthesia (40 mg/kg) with 16 mcg of 6-hydroxidopamine (6-HODA) in the A9 and A10 areas during petilil action and without it. In a month, operated, pseudo-operated and control rats were conditioned to a food-procuring reaction in a T-maze. Injection of 6-HODA both to A9 and A10 areas without petilil made the learning impossible. Fluorescence was lowered both in dopamine and noradrenaline containing brain nuclei. Rats injected with 6-HODA in A9 against the background of petilil did not learn. After 6-HODA injections in A10 in these conditions, the learning worsened but was possible. Fluorescence of dopamine after 6-HODA injection in A9 during petilil action was reduced in the caudate nucleus, and after injection in A10--in n. accumbens and the olfactory tubercle. The obtained results point to a significant role of predominantly nigro-striate system in performance of alimentary conditioned reactions in the T-maze. PMID- 3107238 TI - [Functional hemispheric asymmetry in children with hypersynchronous activity in the EEG. A tachistoscopic study using visuolinguistic stimulus material]. AB - 24 patients of a child psychiatric clinic with focal epileptiform activity located in different brain areas were tested with tachistoscopically presented letter and word stimuli to examine functional hemisphere asymmetry. Children with epilepsy were excluded. No differences were found concerning the lateralisation of the examined functions between the clinical groups and a matched pair nonclinical control group. All children showed an advantage of the left hemisphere in processing the presented visuo-linguistic stimuli. Children with bihemispheric epileptiform discharges showed superior performance on all tasks in contrast to children with left hemispheric discharges and the control group. Results were discussed in the theoretical framework of raised cortical vigilance in these children. Asymmetric hemispheric functions focal epileptiform discharges tachistoscopic study letter/word recognition test. PMID- 3107239 TI - Organization, polymorphism, and regulation of class II genes of the major histocompatibility complex. PMID- 3107240 TI - Immunotoxicology--1985. PMID- 3107241 TI - Interleukin-1: amino acid sequences, multiple biological activities and comparison with tumor necrosis factor (cachectin). AB - Interleukin-1 (IL-1) now refers to a family of polypeptides which are produced by the host in response to injury, infection, and various immunological reactions. To date, two forms have been cloned but there are likely others. Recombinant IL 1s confirm the multiple and diverse biological properties that had been described previously using natural IL-1s. In this review, the cloning approaches for are discussed; in addition, the molecular control of IL-1 synthesis and processing are considered. The various biological activities of recombinant IL-1s are presented and are discussed regarding their clinical relevance. The multiple biological activities of recombinant tumor necrosis factor (cachectin) are compared to those of recombinant IL-1s. PMID- 3107242 TI - [Problems in classification of fractures of the proximal humerus]. PMID- 3107243 TI - [The evaluation of integrity damage following spinal injuries according to the Accident Insurance Law]. PMID- 3107244 TI - [Double-plate osteosynthesis according to the laminated spring principle]. PMID- 3107245 TI - [The status of endoprosthetic management of proximal femoral fractures in Zieglerspital Bern]. PMID- 3107246 TI - [Tibial fractures with loss of bony substance (concerning 3 case reports)]. PMID- 3107247 TI - [Immobilization of leg fractures using Sarmiento's orthosis or a PTB-supported boot cast]. PMID- 3107248 TI - [Base fracture of the 5th metatarsal. Classification and therapy using a strapping bandage]. PMID- 3107249 TI - [Optimal treatment of radial head fractures in relation to age]. PMID- 3107250 TI - [Follow-up of 100 wrist fractures]. PMID- 3107251 TI - [Fracture of the base of the 5th metatarsal bone: treatment using boot cast or zinc paste?]. PMID- 3107252 TI - [Long-term results of surgical treatment and treatment with a walking cast in fresh complex ligament injuries of the knee]. PMID- 3107253 TI - [Detection of mycobacteria in tissue in urogenital tuberculosis]. AB - 121 tissue specimens of the urogenital systems (66 from the kidney, 39 from the epididymis and testis, 8 from the prostate, 4 from the bladder and 4 from the female genital tract) were examined by microscopy, culture and animal experiment on the presence of mycobacteria. In 37 of these specimens (30.6%) mycobacteria were demonstrated, 10 of that only by microscopy and in 27 cases by culture and/or animal experiment. Up to 20 weeks after onset of treatment mycobacteria were demonstrated from the kidney tissue of treated patients by the diagnostic methods mentioned above. After this time mycobacteria never could be demonstrated. There was no correlation between the histological findings and the mycobacteriological investigations. The investigation of tissue specimens on the presence of mycobacteria also from other organs of the urogenital tract is suitable method of the bacteriological proof of tuberculosis, especially in the absence or positive bacteriological findings from the urine or accessory gland secretion for the estimation of species and resistance of these bacteria. PMID- 3107254 TI - [Hygiene of meat production and processing]. AB - Meat becomes unavoidably contaminated already at slaughtering. During storage and processing this contamination is increasing in a considerable degree. Cooling immediately and continuously enables a psychrotrophic saprophytic microflora to propagate. This will provoke characteristic spoilage after a longer period of storage or at interruption of the cooling chain. A limitation of total counts from the early beginning of meat processing increases stability of meat considerably. Potential pathogenic or toxinogenic microorganisms may occur, too. Their origin has to be seen at the living animals and at the meat handlers. These microorganisms may not be allowed a competitive growth within a comprehensive psychrotrophic microflora normally. On the other hand they may get hygienic importance as resistant parts to processing steps or as recontaminants after elimination of accompanying microflora. A good manufacturing practice must be directed by limiting growth criteria for microflora components. These are lower limits of growth temperature, water activity, pH-value or anaerobic condition after packing. A good manufacturing practice may be achieved considering the HACCP-concept: Meat and meat products must be defined as risk carriers according to animal and product specialties. The numerous microflora habitats have to be known very well. Generally the risk factors and especially the critical control points in each production area have to be explained. An effective control during process stages and/or of the final products must be applied. The determination of the total count or of the count of Enterobacteriaceae as indicator organisms may be suitable at the microbiological process control. Index microorganisms may be used at special final products. The practice of processing meat and meat products may be optimized considerably. The most important aspects concerning the questions mentioned before are listed in this paper. PMID- 3107255 TI - Specific nutritional requirements of Lactobacilli spp. from meat. AB - The nutritive requirements of atypical streptobacteria isolated from fresh meat were examined. Niacin and pantothenate were essential for all strains and some strains also required pyridoxal phosphate and riboflavin. Most of them were characterized by their great requirements for aminoacids and their failure to ferment many sugars compared with L. plantarum or L. casei. PMID- 3107256 TI - [A food-borne infection caused by Campylobacter jejuni serotype Lauwers 19]. AB - Report on a outbreak due to contaminated food involving 556 schoolchildren who got their lunch from a school kitchen. The outbreak occurred abruptly without any secondary infectious. Examinations for Salmonellae, Shigellae, Enteritis-coli, Yersiniae and Rotaviruses were negative. However, Campylobacter jejuni were isolated from 105 specimens of faeces in Rostock. Sixty of these strains and another 2 that had been isolated at the same time but had no relation to the outbreak in Rostock, were further differentiated in Berlin-Buch. All of them proved to be Campylobacter jejuni biotype 2. Serotyping according to Lauwers revealed that 58 out of the 60 strains isolated belong to serotype 19. One of the two remaining strains could not be typed, the other was identified as serotype 1. One of the two cultivated strains that were not related to the outbreak in Rostock, was untypable, the other being of serotype 2. Therefore it can be assumed that the outbreak came from the same source of infection. Epidemiological investigations pointed to some food which had been served 6 days prior to the outbreak. The meal had consisted of white cabbage stew with beef. The kitchen supplies the cooked food to several institutions; 3 different dishes being prepared each day, referred to as dish, A, B and C. The institutions receiving dish A - which on November 1, 1985 was the above-mentioned white cabbage stew - actually included several classes of a school as well as a kindergarten. On that particular day however the kindergarten had not been supplied with dish A but, as an exception, with dish B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107257 TI - [Estimating the biological effect of detrimental substances on E. coli with flow microcalorimetry. I. Flow microcalorimetric test systems using microorganisms for antibiotics and chemicals (literature review)]. AB - Flow microcalorimetry has found increasing use in many rather different sections of biological science in order to investigate metabolic reactions accompanied by heat production during the last few years. The microcalorimetric technique seems to be adequate for investigating liquid microbial cultures, particularly. Flow microcalorimetry is preferentially used for testing the effect of antibiotics and to a smaller extend the effect of other chemical compounds on bacteria and yeasts. The test substances are usually added during the logarithmic growth phase of the microbial culture or to cultures of nongrowing cells in glucose buffer solution. There are less reports on the addition of the test substances during the steady heat plateau of a respiring or grown through culture. The received power-time-curves are compared to "control curves" recorded under identical conditions without test substances. Difficulties and errors can be caused by external influences (e.g. changes in room temperature) or by latent processes within the detector and tubes of the calorimeter (e.g. mixing reactions, ad- and desorption, adhesion to and growth on the walls of the tubes, obstruction by clots of cells). A substantial advantage of the microcalorimetric technique as compared to traditional bioassays is the continuous monitoring of the effect, an additional advantage is its quick and simple performance. The sensitivity is comparable to other bioassays of antibiotics. PMID- 3107258 TI - [Estimating the biological effect of detrimental substances on E. coli with flow microcalorimetry. III. Studies using m-cresol in glucose phosphate buffer]. AB - Investigations are carried out to characterize the influence of the phenolic compound m-cresol on the heat production of glucose-respiring E. coli cells suspended in glucose phosphate buffer in a flow microcalorimeter according to the method of Perry et al. (5) The results are usually obtained within one hour. When testing m-cresol by this method thermic irritations occurred. A modified test procedure which largely avoids these troubles is described. The height (Q = heat flow) of the power-time-curves is evaluated 30 min and 60 min after the addition of the test substance. These values are compared to the values obtained from control-curves without any test substance. The 60 min-values seem less variable than the 30 min-values. The minimum effective m-cresol concentrations come to 7.50 mmol/l after 30 min and to 9.37 mmol/l after 60 min. The coefficients of variation are distinctly lower than +/- 10% at concentrations of less than 11.25 mmol/l. The coefficients of variation from 3 to 5 tests can extend +/- 20% both for the 30 min-values and the 60 min-values at higher concentrations (e.g. 15 mmol/l). Under the influence of increasing m-cresol concentrations the germ content in the solution and the heat flow decrease in a similar way. The results indicate that the used flow microcalorimetric technique is suitable to check the effect of a test substance on a test culture within only one hour's time. Possibly, the method can be helpful for pretesting disinfectants. The gathering of further experience with this system seems advisable. PMID- 3107259 TI - [Recent studies on the recolonization of drinking water]. AB - About the re- or aftergrowth in drinking water there are some reports. But there are still no real ideas about the reasons and the colony counts to which the water may rise under practical conditions when there is no external influence. In these investigations drinking water was stored in a reservoir for 3-6 weeks and the increase of colonies was observed. In all six tests there was an increase in the colony count. The maximum counts fluctuated between 8-2000 colonies/ml. The water, a mixture of surface- and groundwater, had not a homogeneous tendency of re- or aftergrowth. The chemical parameters gave no indications to these differences. PMID- 3107261 TI - [Demonstration of Legionella pneumophila in dental units]. AB - 42 dental units in 35 dentist practices were bacteriologically examined. Legionella of the species Legionella pneumophila--SG1 could be isolated from 4 dental units. Infection can occur during inhalation of finest aerosols, which are formed during the use of dental turbines and sprays. PMID- 3107260 TI - Bacterial colonization and occurrence of Legionella pneumophila in warm and cold water, in faucet aerators, and in drains of hospitals. AB - Warm and cold water as well as water from wash basin drains and faucet aerators was examined to determine the number of viable and dead bacteria by culture and by staining and to establish the spectrum of species with special consideration of Legionella pneumophila. The relation between the number of Legionella pneumophila, the temperature, and the iron content of the water was determined in three separate warm water systems. High colony counts (up to 8.9 X 10(5) colony forming units), were detected in both warm and cold water at certain sampling sites. The most prevalent genera were Pseudomonas, Bacillus, Flavobacterium, Acinetobacter, and Moraxella. Legionella pneumophila was found in every building in 35 of 150 warm samples and in 1 of 43 cold water samples. The highest water temperature of a sample containing Legionella pneumophila was 64 degrees C. The correlation between high colony counts and the occurrence of Legionella pneumophila in the samples was not significant. High iron concentrations, however, appear to have a positive effect on the growth of Legionella pneumophila. PMID- 3107262 TI - [Bacterial infection agents in hospitalized patients]. AB - During six months the pattern of microbial isolates has been analysed from 1492 urinary tract infections, from 1445 wound infections, from 451 bronchial secretions, from 3067 blood cultures, from 116 peritoneal swabs and from 39 cerebrospinal fluids. All the specimens investigated were taken from patients of surgical, neurosurgical, internal wards and two intensive care units. In total, the most frequent isolates were grampositive microorganisms like Staphylococus aureus, Straphylococcus epidermidis and Streptococcus sp. of different serotypes. Out of the Enterobacteriaceae Escherichia coli and Klebisella pneumoniae predominated followed by Enterobacter cloacae and indolnegative and -positive Proteus species. The over all isolation rate of Pseudomonas aeruginosa in nosocomial infections was about 10%. In the last time Pseudomonas maltophilia will be isolated more frequently as well as occasional Streptococcus faecium and Corynebacterium JK. Dependent from the site of infection anaerobic bacteria like Bacteroides sp., Peptococcus- and Peptostreptococcus sp. are really important in the infectious diseases. The epidemiological data should be always transmitted to the infection control board. From there preventive measures must be induced. PMID- 3107264 TI - [Water hygiene in the hospital]. AB - After defining what we mean by water hygiene and a short survey of contamination sources for water of drinking-water quality in a hospital, we describe by 2 focal points of water demand, namely dialysis and physical therapy (hydrotherapy pools): at which points and by which means water may suffer from microbiological contamination or by alterations of chemical parameters, which infectious agents and chemical parameters primarily are involved, which measures are required to secure the quality of this water. The major regulations and DIN-standards pertinent to water hygiene are pointed out, and the importance of considering measures of water hygiene for the supply of qualitatively unobjectionable water in the hospital is demonstrated. PMID- 3107265 TI - [Hygiene problems in dental practice with special attention to dental units]. AB - Within a scope of an investigation concerning hygiene-problems in dental practice a longitudinal study was carried out in 20 dental offices with 53 units. In order to guarantee equal experimental conditions and to eliminate variations caused by changing water flow during the day, we took the samples before office hours alternating mondays, tuesdays and wednesdays. Those samples gathered from all handpieces (n = 530) and the drinking water faucets (n = 200) were examined according to the "Trinkwasser-Verordnung" (1986), diagnostics were supplemented concerning special groups of bacteria (see also Table 1). Analyses of copper, zinc and iron were done once during the study. Selecting certain sampling spots (see also Table 2) the surface contamination of the units and the surroundings was examined using the "Rodac"-method (n = 4800). The results of the study may be summarized as follows: The investigation concerning the surface contamination showed under qualitative and quantitative aspects (see also Fig. 10) constant contaminations on the patients' head- and armrests, the operating lamp, cuspidor bowl and hand-wash-basin. In samples taken from the water system of dental units potentially pathogenic bacteria were isolated in 71%, in first place Ps. aeruginosa, followed by Ps. acidovorans and other species of this group. Legionella species occurred sporadically in the units and potable water of 8 offices. On the base of the total germ count (22 degrees C and 37 degrees C) the diagnosis "drinking-water quality" was possible only in 31%. The longitudinal investigation showed, that the contamination of the water system follows different progressive forms regarding extent and quality (see also Fig. 7). Relating to these results in the first step the development of a theoretical model concerning the different influencing factors (quality of water tubes and other devices, variation of temperature, quality of potable water and the effect of ionic exchangers, indirect contamination by patients and dental staff, nature of dental treatment, utilization frequency of the direct handpieces) appears to be necessary. Thus the contamination has to be understood as a developing process determined by specific promotors and catalyzers; in the second step the evaluation of adequate bactericidal and virucidal decontamination procedures fitting into the daily practical needs of dental offices should follow. PMID- 3107263 TI - [Nosocomial virus infections]. AB - Enveloped viruses, e.g. influenza- or varicella viruses may cause highly contagious airborne infections. Their spread is difficult to control, also in hospitals. In the case of influenza and varicella immune prophylaxis and chemotherapy/chemoprophylaxis are possible. This is of particular significance, since varicella and zoster are of increasing importance for immunocompromized patients. Diarrhea is caused to a large extent by viruses. Rotavirus infections play an important role in infancy, and are frequently acquired in the hospital. In a study on infectious gastroenteritis of infants in a hospital we were able to show that 30 percent of all rotavirus infections were of nosocomial origin. Admission of a rotavirus-excreting patient (or personnel) may start a long chain of rotavirus infections on pediatric wards. Even careful hygienic measures in the hospital can hardly prevent the spread of enterovirus infections. Such infections may be severe and lethal for newborns, as shown by us in a study on an outbreak of echovirus 11 disease on a maternity ward. We have recently obtained data on the "stickiness" of enteroviruses on human skin. This could explain essential features of the spread of enteroviruses in the population. PMID- 3107267 TI - [Dental prostheses and dental impressions from a hygienic viewpoint]. AB - Dentures, dental impressions, removable orthodontic appliances and all dental technical devices, which are part of any dental treatment are parts as well of a potential crosscontamination chain in dental treatment. Most of those items do not tolerate heat as a sure sterilization medium. For disinfection, chemical disinfectant solutions may be used as far as they work properly and as they are tolerated by the materials in question. Though, one can report some progress in disinfection of dentures and impressions, there are still questions open depending on safety and/or compatibility of the particular materials. For disinfection of removable dentures chlorine-yielding preparations such as Maranon can be recommended. Peracid preparations, such as Sekusept, Sekusept steril and Dentavon may be useful for disinfection of dental impressions. To do the possible means to reduce the infection risk for all persons involved in the dental treatment, patient, dentist, dental technician and all auxiliary persons. This includes both, active hygiene provisions as sterilization and disinfection, as well as possible passive self protection. PMID- 3107266 TI - [Barriers to the enforcement of hygiene requirements in dental practice]. AB - In a psychological exploration study 40 dentists were interviewed on the basis of an attitude-orientated decision-making model; 20 of them also made dental units in their consulting rooms available to M. Borneff (10) for analysis and examination. Both subsamples are comparable in terms of structure; differences in the way of answering were not detected. The study focuses on the analysis of complex psychological barriers which would permit us to explain and predict unsatisfactory hygienic behavior in dental practice. The following major results deserve attention: Hygiene and infection prophylaxis in dental practice are questions of relatively high current relevance and sensitivity. The dealing with hygienic hazards and related prophylactic measures is relatively varied and indicates that dentists are willing to further receive and absorb information. But the elimination of possible risk factors is impaired by a variety of psychological barriers which do not exist independently from each other and which also tend to reciprocally intensify one another: Barriers for lack of knowledge While interviewees attribute increasing significance to hygiene in the study of dentistry, the compulsory subject hygienics plays a rather minor role within one's individual education. Knowledge in the field of hygiene and hygienic behavior are essentially a question of further training. But sources of information providing additional continued training are used rather sporadically and judged diversely. Incomprehensibilities and inconsistencies in scientific publications, unsatisfactory effectiveness and practicability of possible hygienic measures do not contribute to a coherent, systematic formation of opinion relevant to behaviour. Deficiencies in terms of knowledge also occur in dental assistants who play a crucial role in carrying out hygienic measures in dental practice. Barriers on account of probability Being aware of the essential hygienic risk factors (dental staff and patients, handpieces and angle pieces, dental impression materials, instruments, dental units) and also knowing of possible prophylactic measures the subjective probability that hazards will actually occur in one's own dental practice is low; only in a few individual instances a hazardous case was encountered already once before. The willingness to invest in statistically only probable and remote (in terms of time) risk eventualities, i.e. the readiness to bear objective as well as psychological "costs" without guarantee of amortization, is only slight. Barriers on account of problems.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3107268 TI - [Hand, skin and mucous membrane disinfection in medical and dental practice]. AB - Disinfection of hands, skin or mucous membranes or the mere cleansing of hands have different functions, which should be differentiated clearly. With different cleansing methods dirt will be removed, whereas disinfection methods will eliminate microbial contamination or reduce the resident skin flora. Cleansing of hands removes only a very limited amount of microorganisms and cannot replace disinfection. Skin has to be disinfected when the integrity of the body is harmed. Depending on the tasks which are to be performed, sometimes an immediate onset of action and not a long duration of effect can be desirable. In other cases it is just the prolonged action, even with slow onset, that is required. Furthermore a long-lasting effect can be useful, when recontamination takes place later on. Skin disinfectants can be applied by spraying or swabbing. There are only limited data known over disinfection of mucous membranes and till now there exist no suitable test-methods. Experimental studies have shown no really convincing results, even though sometimes a sufficient disinfection could be seen in clinical practice. This is partly due to the bacteriostatic effect. The problematical nature of recontamination of mucous membranes is naturally very serious, but the adhesion of disinfectants due to the special conditions on mucous membranes usually rather bad. Which procedures have to be applied in particular cases has to be decided after weighting the risks against each other. PMID- 3107269 TI - [Allergens in the household]. AB - As an introduction a survey is given of the great changes the biotope "household" has undergone during the last decades which had quite important consequences regarding the composition and quantity of the allergens found there. Organic substances are of primary importance among the inhalation-allergens: especially animals (insects (housedust mites!) and pets), but also moulds and organic dusts. Inorganic substances, like fumes of cleansers or of formaldehyde, act more as primary irritants and only rarely cause real allergies. Among contact-allergens on the contrary, inorganic substances like metals, cleansers and the like are more often the cause of dermatitis than organic material, but juices of fruits, vegetables and sometimes also of meat or fish can provoke real allergic sensitizations. PMID- 3107270 TI - [Technical solvents in the household and industry]. AB - The scope of prevention within environmental health protection demands to place man into the focus of environmental protection measures. In this connection, also the effects of technical solvents are increasingly discussed. Their use in the fields of trades and crafts as well as in households and for do-it-yourself purposes is indispensable nowadays. As compared to the industrial use, their consumption in these fields is low. The most important fields of application of the solvents in households and trades have been condensed into several tables, and the possibilities of emission into various environmental compartments (e.g. indoor air, outdoor air, sewage) are shown by several examples. As in part considerable emissions of solvents are caused by the users, their application should be minimized as far as possible for reasons of precaution to protect human health and the environment. Finally, the necessity of complex studies and evaluation of the environmental compatibility of solvents is pointed out. Appropriate investigational approaches are described. PMID- 3107271 TI - [Chemical contaminants in food]. AB - Due to a direct material linking between environment and man via breath, food and potable water, toxic substances have always been in the food of man, only modern analytical methods have made it possible to safely register concentrations in the ppb-range and below. This is why we discover more and more potential hazardous substances in food, becoming conscious of the full extent of contamination more and more. Such concentrations make a toxicological evaluation very difficult, most of all when a long-term effect is concerned. There are different reasons for the occurrence of toxic substances in our food. Substances occurring naturally in food like trypsin inhibitors, solanine and cumarin. Substances that are added to food purposely. To these belong artificial dyes and sweetening agents, sulphur dioxide and pesticides resp. herbicides. Substances that are formed during the production, preparation or storage of food like polycyclic aromatic hydrocarbons, peroxides of unsaturated fatty acids, mycotoxins and nitrosamines. Substances that are taken in due to environmental influences, considering primarily the toxic heavy metals lead, cadmium and mercury as well as polychlorinated biphenyls (PCBs). Legislative authorities have taken numerous steps to protect the consumer against food that is detrimental to his health, based mainly on the so-called "principle of prohibition" that stands for the general prohibition of additives as long as they are not formally permitted. The fundamental prohibition of the "Lebensmittel- und Bedarfsgegenstandegesetz" (law for food and requirements) to produce or handle food in such a way that its consumption is qualified to harm the health of the consumer, has an extensive protective effect. This effect is supported by regulation for additives and special directives. An important group of possibly toxic substances in our food are pesticides and their residues. In 1985 1839 pesticides based on 302 active components were officially admitted in the Federal Republic of Germany, 40% of these as herbicides, 23% as insecticides. The investigations of the food control authorities are oriented on the regulation of maximum amounts for pesticides which includes maximum values for about 470 active substances. There is a report on special investigations of the "Landesuntersuchungsamt" (office for the investigation of food and requirements).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3107272 TI - [Food of animal origin that is potentially infected and in danger of becoming infected by contact. (Food hygiene consequences by the example of the occurrence of Salmonella in meat of slaughtered animals and of hepatitis A viruses in mussels)]. AB - Certain pathogenic micro-organisms in or on food of animal origin still constitute a particular hygienic risk. Salmonellae are found chiefly on meat and in meat products including poultry. Most of the infections with salmonellae in men are presumably caused by the consumption of raw products of animal origin. Our stock of slaughter animals is most often latently infected. During the slaughter and the processing meat surfaces are contaminated with salmonellae. Nevertheless a precautionary decontamination of these surfaces is not undertaken. Furthermore contaminations are still ignored by the official microbial meat inspection, and it is still allowed to use the meat for the production of minced meat meant to be eaten raw. Foods are also "infected" when the pathogenic organisms are introduced by contamination. It is not admissible to consider a small amount of salmonellae in food of animal origin as an acceptable lack of security that is to be respected by the consumer. Usual thinking models and customs are to be made dubious. It is shown at the example of raw meat and mussels that the hygiene of food must be optimized by comprising food technology. PMID- 3107273 TI - [The hygiene of keeping dogs in city apartments]. AB - 16 family households with school-aged children and 15 elderly couples without children were questioned about their views on the hygienics of holding dogs in their apartment. The dogs of each household were clinically treated three times at intervals of four weeks. Samples were taken of dog feces and smears were made of the oral mucosa, skin, feeding dishes, water bowls and of their resting places for parasitological, bacteriological and mycological examinations. Families with children had a more positive attitude towards keeping a dog in the household than did elderly couples who had no children. At the beginning of the investigation all dogs were clinically healthy; most dogs had been dewormed and had received the usual vaccinations. On checking for ectoparasites, there were only two cases of dogs with fleas. An examination for endoparasites and the mycological examination were negative except for two unrelated and insignificant cases of dogs with Toxocara canis. The bacteriological examination demonstrated that among the majority of healthy dogs the very low concentration of bacteria of test areas remained unchanged. There was no difference between the two groups of households as far as the concentration of bacteria was concerned. In outbreaks of diseases such as occasional diarrhea and dermatitis there was a large concentration of E. coli and Staphylococcus aureus in all test samples. The lack of adequate hygiene leads to an increase of bacteria and to an extreme increase of pathogenic bacteria (staphylococci, Pseudomonas aeruginosa). During the study no one became sick (including children) and there was no food poisoning with staphylococcus although the dogs' feeding dishes and water bowls stood in the kitchen. Salmonellae could not be demonstrated. An assessment of the results of the study confirms that keeping dogs in city households does not pose a danger to the health of humans when hygienic conditions are good. PMID- 3107274 TI - [Infant nutrition with prefabricated foods]. AB - Hygienic problems with industrially prefabricated foods for infants are rare. Industrial prefabrication has considerably increased safety of infant feeding. Problems may result from preparation for feeding. Least complications occur with ready-to-feed formulae which can be filled immediately before feeding. There may however be pitfalls in the technological preparations of these formulae especially through heating procedures. The use of prefabricated Beikost in powdered from or in containers is hygienically safe and guarantees constant nutrient and vitamin content throughout the whole year. Rewarming may be dangerous. PMID- 3107275 TI - [Animal hygiene and environmental hygiene]. AB - Animal Hygiene has developed historically from the field of Animal Health Care and is as a part of Veterinary Hygiene now about 100 years old. From her very beginning Animal Hygiene has dealt with the influences of the live and inanimate environment on the health of animals an also investigated the reverse developments. From a historical point of view it can be stated that Animal Hygiene has done active research in the field of environmental hygiene ever since. This tendency was intensified by the modern developments of keeping animals in confinements, enlargement of livestock, new kinds of residues like slurry which demanded a change in the management of arable and forage land combined with an increase in the agricultural utilization of residues form the municipal area like sewage sludge and compost made from refuse. Based on selected examples from the field of production and processing of animals the research on Animal Hygiene in the framework of environmental hygiene is described. This refers especially to emissions and other environmental problems (malodor, dust, airborne microbes) which derive from keeping animals in confinements as well as such which are caused by storage and utilization of animal residues (farm-yard manure, urine, slurry). The most serious problems are caused by production and utilization of slurry (transmission of infectious agents, malodors, damages of soils, plants, surface and ground waters by excess fertilization of arable and forage land). It was Animal Hygiene which made most valuable contributions for solving such problems of environmental hygiene. It was also Animal Hygiene which warned of the possible negative environmental influences of disinfectants. Respective investigations were made and recommendations to avoid damages to the environment given. Also in the field of the agricultural utilization of residues from the municipal area (sewage, sewage sludge, refuse composts) Animal Hygiene has developed basic investigation methods whose results were reflected in several legal regulations for environmental protection. PMID- 3107277 TI - [Keeping pets from the psychological viewpoint]. AB - The research data are based on a representative psychological study (280 persons without domestic animals, 345 dog owners and 305 persons keeping other pets in their homes) and on an interdisciplinary pilot study in 30 households provided with dogs. The following major results deserve attention: Man and dog share a relationship of interaction and of mutual dependence. Animals are determined and shaped by man and vice versa. The dog contributes a great deal to the satisfaction of crucial human needs, to quality of life and well-being. As to adequate keeping of dogs suited to the animal there are still deficiencies in terms of knowledge; in addition, discernible tendencies towards humanization in pets frequently forestall desirable behavior. To convey and to enlarge existing awareness and existing behavioral norms in connection with animal-adjusted behavior, adequate feeding, proper care, vaccination prophylaxis but also in connection with personal hygienic necessities in dealing with the pet is therefore of particular significance. The bacteriological as well as the psychological results reveal that if nutrition, care and prophylaxis appropriate to the animal and personal physical hygiene are observed correctly, health hazards for man caused by the animal and vice versa are practically impossible to occur. Traceable pathogenic findings are results of human lapses and shortcomings; in the cases in which pathogenic germs occur the psychological man dog-relationship is less positive the hygienic requirements and standards in connection with dog keeping are less differentiated on account of a limited personal sensitivity to hygiene there is neither constant care nor is time and attention devoted to the dog to the same invariable extent and deficiencies in terms of healthy nutrition become apparent. The relationship between man and animal--similar to human relations--is still characterized by prejudice, lack of information and thus insecurity with regard to correct behavior and also by mistakes and lapses. Particularly the veterinarians are called for--because of the greater impact of personal conversation and communication; not least also on behalf of competence in the field of behaviorism required and expected from them. PMID- 3107276 TI - [Hygienic problems of keeping pets in the Federal Republic of Germany]. AB - Pet animals i.e. vertebrates from fish to mammals are often suspected to transmit germs of various systematic position (viruses, bacteria, fungi and parasites) to human beings. A critical analysis shows that only a very limited number of such organisms can be transmitted from animals to man. Zooanthroponoses with pet animal origin is a very rare phenomenon. Bacteria like salmonellae which were incriminated to be the cause of about 250,000 infections of man per year, particularly of children, in the USA in the early 70th have really no importance in the Federal Republic of Germany. The statistical dates published every year by the "Statistisches Bundesamt" show clearly that only about 1 case in a year can be traced backwards to reptiles in spite of about 50,000 registered cases of human salmonellosis per year. If we compare the number of about 1 million of reptiles in captivity the incidence is very low. Similar relations exist for other germs, too. As an example the choriomeningitis of golden hamsters is often mentioned. In newspapers and other popular publications this infection is said to be extremely dangerous for children but in reality only a few cases were registered years ago. Nowadays precautions in the breeding farms etc. make it very unlikely that such virus transmissions have any practical importance. This situation is comparable with mycosis caused by fungi like Trichophyton which have their origin in certain mammals. Also psittacosis--in form r times not infrequently the cause of sickness and death in man--nowadays is only found sporadically in man, in spite of about the same number of cases in parakeets and other birds. The terrible risk of the disease can be prevented since tetracycline therapy is a successful treatment. It can be stated that zooanthroponoses which have their origin in pet animals is a very rare manifestation, but often misinterpretations are given either ignoring the knowledge of a certain infection or fishing for publicity! One of such examples is toxoplasmosis. About 15 years after the discovery of the life cycle of the protozoon Toxoplasma gondii and the experimentally proven fact that oocysts can be produced only in cats, and therefore transmission to humans is only possible with these stages other animals like rabbits or guinea pigs are still incriminated as the cause of human infections. Apart from the discussed problems and the possibility of transmission of infectious agents from animals to man we must also take into consideration the positive psychological aspects of animal keeping for the hobbyist, and particularly for children.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3107278 TI - [Hygiene in international animal transport]. AB - Animal hygiene at international animal transport can be discussed with respect to three main aspects: The hygienic prevention of contagious diseases where at legislation is to be emphasized. As there are: import and transit regulations, origin and health certificates and precautious disinfection. Some of the latter show the particularity of the sea and air transport. By the means of contagious disease-legislation animals of the respective territory, but also the human are protected. In dependence of the duration of transport, either defined symptoms of a disease can be evident during the transport or at arrival in the destination port, on the other hand animals can be still within incubation time. In the latter case only a quarantine at the destination can provide full efficiency. The curative veterinary aspect. In this special case is referred to experiences with "Enterotoxaemia" of sheep during sea-transportation. The disease leads to heavy losses of animals depending on the duration of the voyage (influence of stress of transport). Preventive measures, like vaccination at beginning of the transport and using superphosphate in the pens, depressed the losses persistent. The aspect of animal protection. Exemplary proposals for sufficient ventilation rates during air transport were given. PMID- 3107279 TI - [9th Dusseldorf Hygiene Seminar. March 1986]. PMID- 3107280 TI - [Hospital infections in changing times]. AB - It has already been known in ancient medicine that diseases with similar clinical picture can occur all at once at a certain place and under certain climatic conditions, and the Hippocratics dedicated a special book of their Hippocratic Scriptures to epidemics. The symptom complex of what is nowadays called "hospitalism", however, could only develop when the first hospitals were founded in early Christian cultures, which means social foundations, which were not at all hospitals like today, but social institutions for the old people, for pilgrims and--only in the third place--an asylum for poor, homeless, ill people. As well as in other places where large numbers of people are crowded together under poor hygienic conditions, e.g. in prisons or on overcrowded ships, in those overcrowded hospitals, which were called "Nosokomeion" in the Byzantine world and thus might well have been institutions where nursing of sick people was done, specific epidemic diseases occurred which were rarely found in individuals living in freedom or at their domiciles. Like all other epidemics, they were thought to be attributed to a miasma transported by the air and resulting from bad vapours, and it was for two milleniums that this remained the explanation for infectiosity. As in the hospitals before introduction of anti- and asepsis wound healing per secundam, i.e. purulence, was regarded as normal and pus was called "Pus bonum and laudabile", which was thought to be the supposition for wound healing and was the reason for the infernal stench which one could smell. One attributed the occurrence of miasma to this component. It was therefore attempted to combat the hospital infections by all means with desodorizing procedures, thus trying primarily to suppress the stench by frequent whitewashing of the rooms, spraying of vinegar, by burning powder and even using precious incense. On the other hand, various infectious diseases could easily be brought into those overcrowded hospitals, where often three up to six patients had to share one bed, so that still in 1865 no less a person than the famous Theodor Billroth (1829 1894) felt himself obliged to warn of the dangers of a stay in hospital. The danger of "hospitalism" or of "nosocomial infection" let the rich refrain from going into a hospital, until the progress in surgery, which was initiated by the introduction of narcosis, allowed surgical treatment only to be effected in hospitals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3107281 TI - [Biological properties of antibiotic-resistant mutants of the mildly pathogenic Rickettsia prowazekii E strain]. AB - The use of R. prowazekii strain E with low pathogenicity as live vaccine against exanthematous typhus is limited by its high specific reactogenicity, which is probably due to the reversion of the virulence of the strain. One of the approaches to the stabilization of the avirulent properties of strain E is obtaining its mutants with stable decreased pathogenic properties. The article presents the data on the infectious properties of R. prowazekii antibiotic resistant strain E mutants obtained in earlier experiments, in respect of chick embryos and laboratory animals, as well as the capacity of this strain for producing immunity to challenge with R. prowazekii virulent strain in guinea pigs. The study has revealed that the erythromycin-resistant mutant of R. prowazekii strain E, induced by nitrosoguanidine (NG), has lower infective capacity for chick embryos, guinea pigs, cotton rats and white mice. The infective capacity of the NG-induced rifampicin-resistant and spontaneous erythromycin-resistant mutants of R. prowazekii strain E is similar to the infective capacity of the initial strain. The rifampicin-resistant and spontaneous erythromycin-resistant mutants of R. prowazekii strain E possess immunogenicity similar to that of the initial strain E, and the NG-induced erythromycin-resistant mutant possesses lower, but sufficiently pronounced immunogenicity despite its decreased infective capacity for guinea pigs. PMID- 3107282 TI - [Relation between natural bacterial colonization and adhesion to human buccal epithelium]. AB - As the results of the quantitative study of Streptococcus salivarius adhering to buccal epithelial cells, three levels of their natural colonization were established: low (less than 20 bacteria per epithelial cell), medium (20-50 bacteria), and high (more than 50 bacteria). The characteristics of natural colonization by S. salivarius inversely correlated with the resistance of epithelial cells to the adhesion of Pseudomonas aeruginosa. In the process of interaction with P. aeruginosa highly adhesive strain, S. salivarius, naturally colonizing the cells of the buccal epithelium, decreased in number 2-10 times up to complete desorption. These results may be regarded as the manifestation of one of the mechanisms regulating the microecological balance in the system of mucous membranes. PMID- 3107283 TI - [Cultivation of the gonococcus in nutrient broths]. AB - The dynamics of the multiplication of gonococci and the parameters of their growth have been studied in the process of batch cultivation in liquid culture media with different content of bovine blood serum. The protective and stimulating action of the serum on the growth of gonococci has been shown. The optimization of the process of cultivation has been carried out; as a result, the growth of test strains in a culture medium containing no serum has been achieved. Phasic changes in the ultrastructure of gonococci in the process of their cultivation in liquid media have been followed. 9- to 12-hour cultures of gonococci grown in liquid culture media have been found the most valuable and physiologically active. PMID- 3107284 TI - [Modelling of the epidemic process of suppurative septic infections using a Pseudomonas aeruginosa bacteriophage]. AB - The method for modeling the epidemic process of pyoseptic infections with the use of P. aeruginosa bacteriophage is proposed. The application of this method in urological and traumatological wards has made it possible to confirm the role of patients as the sources of infection and the part played by instruments and the hands of the medical personnel in its transfer. PMID- 3107285 TI - [Evaluation of transplantable cell lines as a substrate for producing biologically active substances]. PMID- 3107286 TI - [Quantitative evaluation of a population of immunocompetent cells having a receptor for the anthrax protective antigen]. AB - Studies of the number of immunocompetent cells with receptors to anthrax protective antigen in the blood of hamadryas baboons infected with Bacillus anthracis carried out by the rosette-formation technique have shown a statistically significant increase in the number of these cells in the animals as early as 12 hrs after their infection. PMID- 3107287 TI - [Pseudomonas aeruginosa and Proteus antigenemia and antibody formation in mono- and mixed infections in patients with suppurative inflammatory diseases]. AB - P. aeruginosa and Proteus antigenemia and antibody production have been studied in 335 patients with purulent inflammatory diseases. The study has revealed that in the association of P. aeruginosa and Proteus with staphylococci and representatives of the family Enterobacteriaceae the level of antigenemia is considerably lower than in monoinfections or in the association of these microorganisms with streptococci. In mixed infections humoral immune response develops later than in cases of monoinfection. An important role of ecological and physiological relationships between microorganisms in the course of purulent processes and in their influence on the host has been confirmed. The use of the enzyme immunoassay in the clinical practice has made it possible to determine the etiological role of P. aeruginosa and Proteus in the development of suppurative inflammatory diseases, to select adequate immunotherapy, including the use of anti-P. aeruginosa and anti-Proteus plasmas, and to evaluate the effectiveness of treatment. PMID- 3107289 TI - [Effect of thyroliberin on the clinical manifestations of the alcoholic abstinence syndrome]. AB - In a double blind diagnostic study of the reserve thyrotropic function of the hypophysis, the authors have investigated the effect of the thyrotropic releasing hormone (TRH) versus placebo on the clinical manifestations of the alcohol abstinence syndrome in 60 patients with stage 2 chronic alcoholism. TRH and placebo-reactive and resistant symptoms of abstinence have been identified. TRH has a positive effect on some psychopathological and somatovegetative manifestations of alcohol abstinence. It is suggested that the use of TRH, in addition to its therapeutic and diagnostic value, will help to better study-at the clinical level-the role of the peptidergic system in the pathogenesis of alcohol-induced disorders. PMID- 3107288 TI - [Comparative morpho-functional characteristics of the capillary bed of the mammillary bodies and temporal lobe of the human cerebral cortex in young and late middle-aged hypertensive patients]. AB - Using a morphometric technique the author has studied the regional characteristics of compensatory-adaptive reactions of the capillary bed in the mamillary bodies and cortex of the temporal lobe in hypertensive patients who has died in young and old age. It has been found that compensatory reactions of the capillary bed of the cortex fail faster than those of the mamillary bodies under the same conditions. A hypothesis is validated that this phenomenon may account for the tissue changes in the specified areas in young versus old hypertensive patients. PMID- 3107290 TI - [Features of peripheral circulatory disorders in patients with progressive muscular dystrophies]. AB - A total of 135 patients with primary and secondary progressive muscular dystrophies have been studied rheovasographically. On the basis of the findings obtained the authors have identified the main types and peculiarities of peripheral circulation disorders and described the principal pathogenetic mechanisms of their development. The clinical and physiological correlations are presented. The authors show the importance of detected changes in the peripheral circulation for the medical expert evaluation of working ability. PMID- 3107291 TI - Dolichol biosynthesis in rat liver peroxisomes. PMID- 3107292 TI - Systemic lupus erythematosus with rectal stenosis simulating tumour or diverticulosis. Case report. AB - A case of systemic lupus erythematosus (SLE) with focal involvement of the rectum is reported. The lesion roentgenologically resembled a malignant tumour and was resected. Histologic examination disclosed only typical SLE changes in a very restricted area, with the remaining gastrointestinal tract unaffected. This appears to be the first report of focal colitis as a complication of SLE. The case points the importance of suspecting symptoms from any organ system in patients with connective tissue disorders to be manifestations of that underlying pathology. PMID- 3107293 TI - The origin of immunoglobulin diversity. PMID- 3107294 TI - Glucocorticoid modulation of growth hormone secretion in vitro. Evidence for a biphasic effect on GH-releasing hormone mediated release. AB - Glucocorticoids have been shown to have both stimulatory and suppressive effects on GH secretion in vitro and in vivo. In order to study the kinetics of glucocorticoid action on the somatotrope, cultured rat pituitary cells were exposed to dexamethasone for varying periods of time. During short-term incubations (less than or equal to 4 h), dexamethasone inhibited GHRH and forskolin-elicited GH secretion, but during longer incubation periods, the glucocorticoid enhanced both basal and GHRH-stimulated GH release. The inhibitory effect of brief dexamethasone exposure was also seen in cells which previously had been exposed to dexamethasone. In addition, growth hormone secretion from cultured rat and human somatotropinoma cells was inhibited by a brief exposure to dexamethasone. Thus, the nature of glucocorticoid action on the isolated cultured somatotrope is biphasic, with brief exposure inhibiting, and more prolonged exposure stimulating GH secretion. PMID- 3107295 TI - Hemiovariectomy and follicular growth in the immature rat. AB - Female rats were hemiovariectomized on day 1 (T2) or day 10 (T3) after birth. The population of growing follicles in the remaining ovary and the plasma levels of FSH an LH were compared to controls (T1) on post-natal days 20, 30 and 38. There was a non significant trend towards higher FSH and LH levels in hemicastrates. Hemicastration had a significant (P less than 0.05) overall effect on the number of small (1 to 2 layers of granulosa cells) and preantral follicles (more than 2 layers of granulosa cells and diffuse antrum): small follicles were more numerous (P less than 0.05) in ovaries of the T3 group, whereas preantral follicles were more numerous in the T2 group. Atresia was somewhat lower in hemicastrates compared to controls. The observed increase in the whole population of follicles, in the remaining ovary, may be attributed to several factors including a decrease in steroids and inhibin, an increase in FSH and/or a neural discharge signal. The increased number of follicles may constitute a reserve to maintain the characteristic ovulation pattern of the species in later life. PMID- 3107296 TI - Thyrotropin-releasing hormone immunoreactivity in human blood, urine, spinal fluid, amniotic fluid, saliva, and gastric juice. AB - TRH immunoreactivity levels were measured in human blood, urine, saliva, spinal fluid, amniotic fluid and gastric juice. Urinary TRH excretion during a 48-h period was measured in 11 healthy persons. Blood and urinary TRH immunoreactivity were measured at 2 and 5 h, respectively, after administration of 40 mg of TRH. All the samples were prepurified by SP-Sephadex-C-25 cation-exchange chromatography and subjected to reverse-phase high-pressure liquid chromatography (HPLC). TRH immunoreactivity levels were then measured by our TRH radioimmunoassay. The TRH immunoreactivity (TRH-ir) levels found in urine were 14.6 +/- 2.5 pmol/l; in blood 7.5 +/- 2.0 pmol/l; in spinal fluid 2.8 +/- 1.4 pmol/l, and in gastric juice 23.2 +/- 7.1 pmol/l. In all of the amniotic fluid and saliva samples, in almost one half of the blood and spinal fluid samples, and in almost one third of the gastric juice samples, TRH-ir was below the detectable limit. In blood and urine samples taken after oral administration of TRH, TRH-ir was eluted at the same time as synthetic TRH. The recovery of synthetic TRH added to the samples ranged from 36 to 99%. In all of the biological fluid samples, endogenous TRH-ir was eluted at the same time in HPLC, at 15-18 min, as was synthetic TRH which had been added to the samples. Urine was found to contain two TRH immunoreactive peaks, the second of which was eluted at the same time as synthetic TRH. No diurnal variation in urinary TRH excretion or TRH-ir levels was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107298 TI - Effect of serotonin on basal and TRH-induced release of prolactin from rat pituitary glands in vitro. AB - The effect of serotonin on the release of prolactin (PRL) was studied in vitro. Anterior hemipituitary glands from ovariectomized rats were incubated for 1 h in the presence of different doses of serotonin. Serotonin added into the culture medium caused a significant increase in basal PRL release. The effect was dose related between 10 and 30 nmol/l serotonin, but responsiveness declined towards basal levels with higher concentrations. When studied as a function of incubation time, basal release of PRL was significantly increased up to 1 h but decreased thereafter. Serotonin also enhanced the release of prolactin induced by 30 nmol/l thyrotropin-releasing hormone (TRH), at all doses tested. A serotonin concentration of as little as 30 nmol/l was already effective. A significant response was seen at 15 min and further increases occurred during the following incubation periods. Serotonin (approximately EC50 4.6 X 10(-8) mol/l) was less potent than TRH (EC50 about 1.2 X 10(-8) mol/l) to increase basal PRL release. On the other hand, the indole amine appeared to act with similar potency in stimulating PRL release both basal and TRH-induced. In addition, the combined effect of the releasing agents was found to be additive. These results suggest that serotonin and TRH could act through separate mechanisms. Methysergide, a serotoninergic blocking agent, had no effect on the in vitro PRL release either basal or TRH-induced, but it completely blocked that evoked by serotonin suggesting that serotonin may interact with specific receptors on the lactotropes. These findings clearly demonstrate that serotonin may stimulate the release of PRL by acting directly at the pituitary gland level. PMID- 3107297 TI - Serum free thyroid hormones in different degrees of hypothyroidism and in euthyroid autoimmune thyroiditis. AB - Serum total and free T4 and T3, thyroxine-binding globulin (TBG) and TSH, basal and 20, 30 and 60 min after TRH (200 micrograms, iv), were evaluated in 125 hypothyroid patients (38 with severe, 23 with mild, and 64 with subclinical hypothyroidism), in 35 euthyroid subjects with autoimmune thyroiditis, and in 51 healthy controls. T4/TBG and T3/TBG ratios were also calculated. A significant decrease in all indices of thyroid function except for T3 occurred simultaneously with a significant increase in basal and TRH-stimulated TSH levels from healthy subjects to subclinical hypothyroids, from subclinical to mild and from mild to severe hypothyroids; euthyroid patients with autoimmune thyroiditis did not differ from healthy subjects. All severe hypothyroid patients had low T4 as well as free T4 (FT4), free T3 (FT3), T4/TBG and T3/TBG ratios, but among mild and subclinical hypothyroids direct determination of FT4 and FT3 proved to be a better index of thyroid function than determination of T4 and T3 even after correction for TBG levels. FT4 was the most commonly abnormal index (19 of 23 subjects with mild and 14 of 64 with subclinical disease). Regression analysis showed that FT4, T4/TBG ratio, T4, and FT3 had a significant inverse correlation with TSH in hypothyroid patients. Discriminant analysis showed that among the thyroid parameters, FT4 is the variable which discriminates best between control subjects and the 3 groups of hypothyroid patients. These data extend previous reports and in a large series of patients confirm the biological meaning and the clinical value of direct measurement of serum free thyroid hormones in hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107300 TI - Cholinergic mediation of growth hormone secretion induced by thyrotropin releasing hormone in cirrhotic patients. AB - In order to evaluate the possible involvement of muscarinic cholinergic receptors in the GH response to TRH in patients with liver cirrhosis, 8 males with post hepatitic cirrhosis and 11 males with post-alcoholic cirrhosis were primed with the anticholinergic agent pirenzepine and tested with TRH. In addition, 10 male patients affected by piecemeal necrosis were tested in a similar manner. High basal concentrations of GH were found in all groups. None of the patients with piecemeal necrosis responded to TRH, whereas in patients with post-hepatitic and in post-alcoholic cirrhosis, TRH induced a significant rise in GH levels. The priming with pirenzepine (40 mg given iv 10 min before TRH) completely blocked the TRH-induced GH increase, but did not affect the TRH-induced TSH release. These data suggest that a muscarinic cholinergic pathway is involved in the anomalous response of GH to TRH in patients with liver cirrhosis. The lack of effect of pirenzepine on the TRH-stimulated TSH release suggests that the muscarinic cholinergic mediation is peculiar for the effect of TRH on GH secretion. PMID- 3107299 TI - Foetal steroid binding protein in British and Japanese women. AB - In order to examine the newly-discovered sex-steroid binding protein, foetal steroid binding protein (FSBP) in different populations, its binding characteristics and its level were studied by two-tier column ligand binding assay and enzyme-linked immunosorbent assay (ELISA) respectively. In 10 Japanese premenopausal women, analysis of 5 alpha-dihydrotestosterone (DHT) binding in the Cibacron Blue 3GA-Sepharose 6B portion of the column showed a rising plateau pattern with a mean maximum binding of 31.1 +/- 7.41%, whereas of 9 similar British women, 8 displayed unsaturable, non-cooperative binding of 11.6 +/- 8.22% (P less than 0.01). After partial purification of FSBP in these samples, the protein exhibited saturable binding kinetics, median binding 25 (interquartiles 23-34) and 19 (13-25) nmol DHT/l in Japanese and British women, respectively (P less than 0.05). By analyzing FSBP by ELISA in 56 Japanese (45 premenopausal) and 59 British (25 premenopausal) women, higher levels were obtained in the whole Japanese group (P = 0.0016) and in the premenopausal Japanese women (P = 0.018) than in their British counterparts. In both nationalities, FSBP levels were higher in premenopausal women, and there was a significant negative correlation of FSBP with age in both populations, particularly in postmenopausal women. FSBP levels did not correlate with weight, parity, sex hormone binding globulin or albumin levels. The influence of FSBP on free steroid levels remains unclear, but some relationship with ovarian function seems a possibility. PMID- 3107301 TI - A lesson from IVF endocrinology: the importance of the follicular phase to success and failure in non-IVF cycles. AB - Sixty-three patients treated with exogenous gonadotropins for a total of 232 non IVF cycles were monitored by serum E2 and/or total urinary estrogen excretion. The endocrine profile of follicular phase during HMG-HCG stimulation was evaluated with regard to an effect on the pregnancy rate. Six different follicular phase patterns were observed: A-profiles (daily exponential increase of sE2 or total urinary estrogen values followed by a sustained exponential increase on the day after HCG injection) seem to be necessary to obtain pregnancy, being followed by conception in 21.5% of all cases. Other profiles have lower conception rate (10%); no conception occurred when non exponential E2 rise was observed. The different responses are not related to total dosage of HLG administered. Patients who were treated for hypogonadotropic hypogonadism had a high pregnancy rate (80%) even in absence of post-HCG estrogen rise (G-endocrine profiles. Women aged 35 years must have significantly higher doses of gonadotropins to obtain A-profiles. Monitoring by E2 seems to be more adequate than the TUE only (conceptual pregnancy rate/cycle of 15.25%, versus 10.34%). In conception cycle, midluteal E2/P ratio never exceeds 50. PMID- 3107302 TI - A direct action of kallikrein on spermatozoal motility? AB - Semen samples from infertile normozoospermic and slight to moderate asthenozoospermic subjects were tested in parallel with and without kallikrein (dry substance) by the Kremer's capillary tube test. Penetration in human midcycle cervical mucus and AB Rh + serum was evaluated. Kallikrein increased spermatozoal penetration into cervical mucus after 3 hrs incubation (p 0.01 in normozoospermic subjects). PMID- 3107303 TI - Aetiopathogenesis of coeliac disease. PMID- 3107304 TI - [Esophageal lesion caused by drugs]. AB - Two cases of esophageal injury secondary to drugs are hereby presented, reviewing the different types of drugs, predisposing factors, physiopathology and complications. PMID- 3107305 TI - Serial studies of bone marrow-derived fibroblastoid colony-forming cells and granulocyte/macrophage precursor cells in patients with acute leukemia. AB - Bone marrow-derived fibroblastoid colony-forming cells (CFU-F) and granulocyte/macrophage precursor cells (CFU-GM) were studied in patients with acute leukemia. The numbers of CFU-F and CFU-GM were significantly lower in patients with acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) at diagnosis than in normal subjects, although patients with AML had a very wide range of CFU-F colony-forming efficiency. However, a suppressive effect of leukemic cells on normal CFU-F colony formation was not observed. CFU-F and CFU GM in patients with acute leukemia recovered to normal levels when complete remission (CR) was achieved and decreased again at relapse. Serial studies showed that the increase in CFU-F preceded the recovery of CFU-GM. In AML, furthermore, patients who achieved CR had a higher number of CFU-F than patients without CR, suggesting that the CFU-F level at diagnosis may contribute to the prediction of the likelihood of remission induction in patients with AML. PMID- 3107307 TI - Anaplastic myeloma as extramedullary relapse of multiple myeloma in remission. Case report and review of the literature. AB - Anaplastic myeloma represents a rare variety of multiple myeloma, with poor prognosis and no response to therapy. 56 cases reported in the literature are reviewed and one case evaluated with immunohistochemical techniques is described. This case is of special interest in the following points: the anaplastic myeloma arose in extramedullary sites in a patient with typical multiple myeloma in remission; differential histological diagnosis between anaplastic myeloma and immunoblastic lymphoma was very difficult without immunohistochemical techniques; the anaplastic phase presented an atypical neurologic feature, the Collet-Sicard syndrome, and the treatment with radio-chemotherapy (including adriamycin) did not induce any clinical improvement. PMID- 3107306 TI - Treatment of severe aplastic anemia with combined immunosuppression (antithymocyte globulin and high-dose methylprednisolone). AB - Fifteen patients with transfusion-dependent severe aplastic anemia (SAA) were treated with combined immunosuppression consisting of horse-antithymocyte globulin (ATG; Atgam, Upjohn) and high-dose 6-methylprednisolone (MP). Oxymetholone was scheduled for 2 years but was discontinued in 7 patients after 10-385 days due to liver toxicity. Serious side effects usually seen in ATG monotherapy were rare during combined immunosuppression. Currently 12 of 15 patients are alive 110-1,275 days (median 475.5) after start of treatment. One patient has received too short treatment to be evaluated. All the others are transfusion-independent. Three patients died; two from septicemia before hemopoietic recovery could be expected and one after relapse. Our results confirm that the addition of high-dose MP abrogates the side effects of ATG monotherapy, and the addition of MP does not counteract, but rather enhances the beneficial effect of ATG in SAA. We recommend combined immunosuppressive treatment with ATG and high-dose MP as a highly feasible, safe and effectful therapy for patients with transfusion-dependent SAA. PMID- 3107308 TI - Acute hematotoxicity of oral benzo(a)pyrene: the role of the Ah locus. AB - Our results show a marked acute hematotoxicity of oral benzo(a)pyrene (BaP) in D2 mice as well as the extreme resistance of BDF1 individuals to bone marrow toxicity induced by oral BaP. Continued oral BaP produced severe bone marrow depression in D2 mice affecting all myelopoietic lineages, but produced only moderate bone marrow depression in BDF1 mice affecting erythropoiesis only. Pluripotent hematopoietic stem cells were almost completely destroyed in D2 individuals, but only reduced to approximately 40% in BDF1 individuals after 7 days of BaP. D2 mice were killed by 13 days of continued oral BaP, but BDF1 mice were still alive and in good condition even after 19 days of continued oral BaP. Analysis of the bone marrow and peripheral blood changes showed that severe toxic chemical bone marrow depression in D2 mice by continued oral BaP cannot serve as an experimental model system of acute aplastic anemia. PMID- 3107309 TI - Severe pancytopenia due to copper deficiency. Case report. AB - A patient with copper deficiency and renal failure was suffering from pancytopenia. Marrow examination showed cytoplasmic and nuclear vacuolizations of the erythroid and myeloid series. These abnormalities disappeared after oral copper therapy. Possible mechanisms causing the pancytopenia are discussed. Copper supplementation is needed for patients receiving dietary changes. PMID- 3107310 TI - Severe aplastic anaemia following hepatitis A. AB - A 3-year-old child developed severe aplastic anaemia following hepatitis A. Since no HLA-compatible donor was available, he was treated with oxymetholone, antithymocytic globulin and methylprednisolone, but no haematologic recovery was observed and he consequently died of pneumonia. Although the association of aplastic anaemia and hepatitis A has already been recognized, this patient represents the first case of aplastic anaemia in which the previous hepatitis A has been well documented. PMID- 3107311 TI - Periodical appearance of erythropoietin-independent erythropoiesis in chronic myelogenous leukemia with cyclic oscillation. AB - A patient with Ph1-positive chronic myelogenous leukemia (chronic phase) had a cyclic oscillation in white blood cells, platelets and percent saturation of transferrin. The cycle comprised about 70 days. The number of circulating granulocyte-macrophage colony-forming units (CFU-GM) oscillated with the same phase, while that of bone marrow CFU-GM and erythroid colony-forming units (CFU E) oscillated in a reverse phase. At the nadir, we observed an abnormal increase in bone marrow endogenous CFU-E (e-CFU-E). An erythropoietin (Epo) dose-response curve of CFU-E showed a high Epo-sensitivity. Anti-Epo rabbit serum did not inhibit the e-CFU-E colony formation. This indicates that Epo-independent erythropoiesis occurs periodically at the nadir. It is suggested that the interactions between the abnormal stem cell and the hematopoietic regulating system cause cyclic oscillation. PMID- 3107312 TI - Cold agglutinins in parenteral drug-addicts positive for HIV antibody. PMID- 3107313 TI - Cataract after busulphan therapy. PMID- 3107314 TI - Hematopoietic effects of continuous intravenous infusion of mice with growth factors produced by the WEHI-3 cell line. AB - A method for continuous intravenous infusion of unanesthetized adult C3H/HeJ or Wx/Wv anemic mice was designed using cage immobilization and a tail vein catheter connected to a model 940 Harvard infusion pump. Infusates included: WEHI-3 cell line dialyzed, 5 times concentrated conditioned medium containing multi-colony stimulating factor (C-SF) interleukin 3 (IL-3); purified murine IL-3; bacterial endotoxin; serum-free medium, or normal saline. Mice were monitored at days 5-7 after infusion for complete peripheral blood counts and production of granulocytes in vitro by explanted marrow in long-term bone marrow cultures. We observed a stimulatory effect of WEHI-3 conditioned medium infusion that was not attributable to endotoxin and produced significant increases in peripheral blood WBC count and neutrophils, colony-forming units in spleen and numbers of granulocyte/macrophage colony-forming unit culture responsive to both C-SF-1 (L cell C-SF) and multi-C-SF in vitro. This infusion method should prove valuable for test of the in vivo effects of purified growth factors and molecularly cloned hematopoietins. PMID- 3107315 TI - Japanese patients with leukaemia following the use of Thorotrast including a patient with marked chromosomal rearrangements. AB - It is estimated that 20,000-33,000 persons have been injected with Thorotrast in Japan. By August 1984, 12 patients with leukaemia following the use of Thorotrast have been reported. Their clinical and haematological data indicate that most of the patients were males over 50 years of age and that the most frequent type of leukaemia involved the stem cells common to the granulocytic, erythroid and/or megakaryocytic lines. This assumption was supported by the evidence of marked chromosomal rearrangements in 100% of the cells from the bone marrow in our case. The median latent period from the administration of Thorotrast to the onset of leukaemia in Japan was 35 years, ranging from 16 to 45 years, which indicates that patients who were injected with Thorotrast should be carefully followed up in the future. PMID- 3107316 TI - A case of acute myelogenous leukaemia associated with eosinophilia: cytogenetic study of eosinophilic colonies showing the origin of the normal clone. AB - We describe a case of acute myelogenous leukaemia presenting with remarkable eosinophilia in relapse. Since the patient had chromosomal abnormalities, haemopoietic as well as eosinophilic colonies grown in culture were cytogenetically analysed to determine the origin of the eosinophils. Eosinophilic colonies as well as erythroid bursts revealed a normal karyotype, while a short term culture of peripheral blood cells in relapse revealed an abnormal karyotype which had been observed before treatment. These data clearly demonstrate that the eosinophilia in this case originated from a normal clone. The cytogenetic analysis of eosinophilic colonies is a useful technique for the definite diagnosis of eosinophilic leukaemia or reactive eosinophilia in patients having marker chromosomes. PMID- 3107317 TI - Stimulation of human eosinophilopoiesis by hydrocortisone in vitro. AB - Excess hydrocortisone (HC) evokes neutrophilia and eosinopenia in man. In addition, the hormone enhances human granulopoiesis in vitro at physiological as well as pharmacological concentrations. This study addressed the prospect that HC exerts opposite effects on the precursors of neutrophils and eosinophils, stimulating the former and inhibiting the latter. Experiments conducted on unseparated bone marrow (BM) cells demonstrated an increase in eosinophil clonogenesis in vitro with the addition of HC to the culture system. Secondary cultures, established from such primary harvests, revealed that HC had a direct impact on the clonogenic cells. Furthermore, administration of HC to normal subjects, at a dose which resulted in consistent eosinopenia, prompted an increase in the generation of eosinophil clones from peripheral blood cells ex vivo. Thus the hormone stimulates production of both neutrophils and eosinophils. Previous reports of opposite effects appear to have resulted from deficiencies of growth factors in the cell cultures. The contrasting effects of HC on neutrophil and eosinophil concentrations in the peripheral blood are more likely due to opposite effects on the distribution of these terminally differentiated cells in the circulation and extravascular tissues. PMID- 3107318 TI - Protein C and antithrombin III in polytransfused thalassemic patients. AB - Seventy-four patients with beta-thalassemia major were studied to test the hypothesis that a deficiency of protein C (PC) and antithrombin III (AT III), both antithrombotic proteins, could contribute to the pathogenesis of CNS thromboembolic lesions. In 70 patients, PC levels were found to be significantly lower than normal, whereas AT III activity was found to be lower only in 41 patients. The lowest values of PC and AT III were found in older splenectomized patients, a low PC value only was found in chronic hepatitis patients. Prothrombin time and fibrinogen were found to be particularly abnormal in patients with chronic hepatitis and without spleen. A relatively poor correlation was observed between PC and AT III (p less than 0.02). PC correlated with age (p less than 0.001), transfusional iron (p less than 0.001) and ferritin (p less than 0.001). It also correlated with serum albumin (p less than 0.001), prothrombin time (p less than 0.001) and fibrinogen (p less than 0.02) and with serum transaminases (GPT) (p less than 0.001). The same indexes correlated less significantly with AT III activity. Nevertheless, only 2 of our patients had CNS thromboembolic complications. It is probable that low clotting factors, hyperfibrinolysis and thrombocytopenia (which are common in chronic liver disease) could have the opposite effect on hemostasis from that of low levels of anticoagulant proteins such as PC and AT III. PMID- 3107319 TI - Suppression of hemoglobin H in disorders of iron metabolism. AB - Disorders of iron metabolism affect the expression of hemoglobin H in hemoglobin H disease. Two cases of iron deficiency with reduced synthesis of hemoglobin H are described in the literature. We report two more cases, one with anemia of chronic disease and another with alcoholic sideroblastic anemia where the hemoglobin H was not detected at presentation and appeared after treatment of the underlying disorder. The pathogenesis of suppression of hemoglobin H is discussed. PMID- 3107320 TI - A retrospective analysis of a consecutive series of patients splenectomized for various hematologic disorders. AB - At our hospital, 47 out of 184 consecutive splenectomies performed over 7 recent years were carried out on patients afflicted with various hematologic diseases. The results of these 47 splenectomies were the subject of a careful retrospective analysis. The majority of the splenectomies (81%) were therapeutic. Cytopenia, particularly thrombocytopenia, was the most common indication for surgery. As a whole, good therapeutic responses with rapid improvements in peripheral blood picture and/or diminished symptoms of pressure discomfort from an enlarged spleen were obtained. There was no peri- or postoperative mortality; 23% major and 26% minor postoperative complications were recorded. In patients with perioperative bleeding and various postoperative complications, the spleens were larger than in subjects who run an uneventful peri- and postoperative course. During the follow up period, 4 septicemias occurred in 3 patients. In 2 of these patients, the septicemias coincided with a cholecystitis and a pneumonia, respectively. None of the infections was lethal. It is concluded that elective splenectomy for hematologic disease in well selected and carefully prepared patients is beneficial and can be performed without mortality or major hazards. PMID- 3107321 TI - Danazol therapy in refractory chronic immune thrombocytopenic purpura. AB - We report our experience with danazol in the treatment of patients with refractory immune thrombocytopenic purpura (ITP). The effects of this drug were investigated in 10 patients, 6 males and 4 females, aged from 40 to 85 years, (median 58 years), with a platelet count below 50 X 10(9)/l. The patients had previously been treated with steroids; one of them had also been unsuccessfully splenectomized. Danazol was administered at a dosage of 600 mg/day for 3 months. Before and after treatment, detection of antiplatelet antibodies was performed. Seven patients were treated for 3 months. One of them showed a transient increase of platelet count, in the others, no significant rise was noted. Six patients experienced side effects during treatment. We think that danazol does not appear to be an alternative therapeutical approach in refractory ITP. PMID- 3107322 TI - Screening for hemoglobin C using Technicon H-6000: the effect of formalin. AB - It has recently been shown that the automated H-6000 cell counter is unable to correctly process blood samples containing hemoglobin C. In this paper, we report that formalin is responsible for the failure of red blood cell lysis in the H 6000. PMID- 3107323 TI - Large-cell lymphoma presenting as acute cholecystitis. AB - A 62-year-old woman presenting with a clinical picture of acute cholecystitis was found to have lymphoma upon pathological examination of the gallbladder. Such a presentation of large-cell non-Hodgkin's lymphoma is unique and has not been described before. PMID- 3107324 TI - Autoimmune hemolytic anemia associated with IgA--diagnostic and therapeutic aspects in a case with long-term follow-up. AB - A 51-year-old woman presented with superficial thrombophlebitis and severe hemolytic anemia. The initial direct antiglobulin test using a broad-spectrum antiserum for screening was negative. Later testing with monospecific antisera revealed the rare finding of an autoimmune hemolytic anemia (AIHA) associated with IgA autoantibody. In IgA-AIHA the direct antiglobulin test with a broad spectrum antiserum may be falsely negative, because a standardized anti-IgA level is not compulsory. This case illustrates the diagnostic significance of monospecific antisera in IgA-AIHA. Our patient responded well to high-dose steroids, but due to repeated exacerbations this treatment could not be tapered. Splenectomy was performed 19 months later. Since then the AIHA remained in remission, even after steroids were stopped, and although the direct antiglobulin test continued to be positive for IgA and became positive again for C3d. Available data about pathogenesis and therapy of IgA-AIHA are reviewed. PMID- 3107325 TI - Downgrading of non-Hodgkin's lymphoma following chemotherapy. AB - A case of high-grade non-Hodgkin's lymphoma (malignant lymphoma centroblastic) is presented which, following chemotherapy, manifested low-grade histology. The importance of repeated biopsies in cases of persistent or recurrent disease following therapy for lymphoma is emphasized. PMID- 3107326 TI - Cytochemistry of N-acetyl-beta-glucosaminidase in normal and leukemic T cells. AB - A cytochemical study of the N-acetyl-beta-glucosaminidase (NABG) activity in normal and leukemic T cells was carried out to ascertain any relationships between cytochemical reactivity and membrane phenotype. Under normal conditions, most T4-positive cells, defined on the basis of monoclonal antibodies and immunogold, were characterized by focal reactivity. In chronic T lymphoproliferative disorders, the reaction product of T4-positive cells consisted of a single coarse granule, while T8-positive cells demonstrated many scattered granules. In all cases of acute T cell malignancies, lymphoblasts were positive with a single coarse granule or many coarse and small granules located at one pole of the cell. PMID- 3107327 TI - Polyarticular pneumococcal pyarthrosis in a young haemophiliac. AB - A case of pneumococcal pyarthrosis involving multiple joints in a moderate haemophiliac is reported. To our knowledge this is the second report of this rare complication in the English literature. Infection should be considered in an acutely inflamed joint in a haemophiliac with hyperpyrexia and unresponsive to replacement therapy. A review of the literature and our observation in this case highlight some criteria that could be used to diagnose this rare but debilitating complication early. PMID- 3107328 TI - [Diagnosis of radionuclide uptake using a whole body counter]. AB - Measurements of whole body radioactivity are performed at our department using a shadow shield whole body counter with automated gammaspectrum analysis. After the radioactive fall-out in Austria due to the reactor accident in Chernobyl the instrument has mainly been used for the assessment of the radiation level in the general population. Amongst the radionuclides incorporated 131-I and 137-Cs had the highest activities. The results of our measurements are summarized in two graphs. At present an increase of 137-Cs activity in the population is clearly observed. PMID- 3107329 TI - Plasma clearance of fat emulsion during continuous heparin infusion. AB - Intravenous fat tolerance was tested in two groups of patients given a continuous i.v. infusion of heparin for several days. One group of 11 patients with deep vein thrombosis (DVT) of the leg was given 25,000-35,000 IU heparin daily for 4-5 days. The other group comprised 10 patients who had central venous catheters (CVC) for total parenteral nutrition. These patients were given 20,000 IU heparin daily for 6 days as prophylaxis against CVC-related thrombosis. In the DVT group heparinization was associated with a 44% decrease in plasma fat removal capacity (P less than 0.05). This reduction persisted for 2 days after the discontinuation of heparin therapy. In the CVC group the plasma fat removal capacity decreased by 29% during heparinization (P greater than 0.05, NS). During heparinization activated partial thromboplastin time was more than three times the basal value in the DVT group but less than twice those in the CVC group. One week after the heparin therapy the serum triglyceride levels were higher in both groups compared with initial values (DVT group: 1.2 +/- 0.2 s.e. mean vs. 1.7 +/- 0.3 mmol/l; P less than 0.05. CVC group: 1.0 +/- 0.1 vs. 1.4 +/- 0.2 mmol/l; NS). The possibility that full-dose heparinization reduces plasma fat removal capacity and that this may be due to a partial depletion of lipoprotein lipase stores is discussed. PMID- 3107330 TI - Mucopolysaccharidoses and anaesthetic risks. AB - The purpose of this review is to asses the current knowledge of mucopolysaccharidosis (MPS), with reference to the serious complications which may arise in connection with anaesthesia and operation. MPS consists of a heterogeneous group of hereditary diseases which are characterized by an abnormal accumulation of mucopolysaccharides, especially in cartilaginous and bone tissue. Because of their progressive and disabling nature, frequent surgical intervention is common, and is associated with a high degree of per- and postoperative risk. The clinical manifestations of MPS are frequently dwarfism, scaphocephaly, grotesque facial features with snub nose, hypertelorism, macroglossia and dental anomalies. The chest is deformed by pectus carinatum or excavatum, club-formed ribs and kyphosis with gibbus. Furthermore, cardiomegaly, abdomen pendens, hepatosplenomegaly, umbilical hernia, corneal clouding, conductive deafness and subnormal intelligence are common findings. Prior to operation, patients should be thoroughly evaluated through clinical examination and laboratory investigations. In particular, lung function should be optimized by lung physiotherapy and treatment of airway infections. When inducing general anaesthesia, spontaneous respiration is recommended until the patient has been intubated, as airway anomalies, bleeding and salivation may make intubation extremely difficult. Local or regional anaesthesia is often preferable, though age and mental status are relative contraindications. When used in combination with careful sedation, many problems may be overcome. Postoperatively, it is important to treat stagnation of secretions and airway infections with lung physiotherapy positive end-expiratory pressure, and antibiotics. In connection with anesthesia, it is vital to monitor the patient carefully before, during and after anaesthesia. PMID- 3107331 TI - Effects of rectal thiopentone and methohexitone on carbon dioxide tension in infant anaesthesia with spontaneous ventilation. AB - The influence of rectal administration of barbiturates on PCO2 during mask anaesthesia with spontaneous ventilation was studied in 72 infants. The age of the patients ranged between 6 and 24 months and they were all subjected to minor paediatric surgery. The patients were divided into four equally large groups: a control group receiving no premedication, a group receiving rectal thiopentone 30 mg X kg-1 and two groups receiving methohexitone either 20 or 30 mg X kg-1. In all patients PCO2 was measured in an arterialized capillary blood sample obtained during stable anaesthesia with oxygen, nitrous oxide and halothane before and after surgery. After rectal induction with barbiturates, the mean PCO2 was significantly higher in the different barbiturate groups than in the control group (P less than 0.05). The mean PCO2 value +/- s.d. in kPa for the control group was 5.6 +/- 0.7, for the group receiving thiopentone 30 mg X kg-1 6.5 +/- 1.6, for the groups receiving methohexitone 20 or 30 mg X kg-1 6.1 +/- 1.2 and 6.3 +/- 1.1, respectively. It is concluded that the combination of rectal induction with barbiturates and mask anaesthesia with oxygen, nitrous oxide and halothane carries an increased risk of hypoventilation in infants under 2 years of age. PMID- 3107332 TI - Biochemical anatomy of human bone: comparative study of compact and spongy bone in femur, rib and iliac crest. AB - Using EDTA extraction procedure, compact and spongy bone from human femur, rib and iliac crest were compared in terms of their content in collagen, sialoprotein, proteoglycan and carbohydrate. The bone matrix sizes displayed significant variations, the femur having the smallest size and iliac crest the largest one. No significant difference in the matrix size has been found between the spongy and compact bone. The EDTA extractability of the spongy bone was higher than that of the compact bone, with femur showing the lowest extractability. The collagen content of the 3 bones studied was similar although the femur had slightly lower values. The sialic and uronic acids and hexose contents were higher in the femur than in the rib and iliac crest. The collagen/hexose, collagen/sialic acid and collagen/uronic acid ratios in the bone matrix were highest in the iliac crest and lowest in the femur, suggesting that alterations in the amounts of bone matrix can affect the mechanical properties of different parts of the bony skeleton and vice versa. PMID- 3107333 TI - [Stuporous state in an epileptic treated with sodium valproate. Diagnostic problems]. AB - The authors report a case of stupor secondary to valproic acid, in a patient treated with this drug and phenobarbital for a complex partial form of epilepsy. The pathogeny of this rare complication is discussed. In this patient, a paradoxical epileptic reactivation is excluded, and the authors favor a metabolic mechanism: either hyperammoniemia or a perturbation in cerebral neuro-transmitter systems are proposed. PMID- 3107334 TI - Regional cerebral blood flow during cortical spreading depression in rat brain: increased reactive hyperperfusion in low-flow states. AB - The purpose of the present study was to characterize the initial vascular events accompanying cortical spreading depression (CSD) of the rat brain. Regional cerebral blood flow (rCBF) was measured during the first 1-2 min of CSD using 14C iodoantipyrine autoradiography. The material included a reference group, and 4 groups where rCBF was altered by indomethacin treatment, hypo- or hypercapnia, or one previous episode of CSD. rCBF did not change prior to, or during the onset of CSD. Thirty seconds later, rCBF increased depending on the pre-existing level of blood flow, i.e. the rise of rCBF was pronounced at depressed flow levels, but small or absent at normal or high flow levels. The prevalent view that CSD is intimately associated with vasodilatation was accordingly not supported. The activated rCBF in normocapnic rats ranged between 93 and 175 ml/100g/min, supranormal values were the exception rather than the rule. The rCBF rise, when present, probably succeeds a period of brain hypoxia, and should be classified as a reactive hyperfusion. The results together with earlier clinical and experimental findings, support that CSD may serve as experimental migraine model. PMID- 3107335 TI - Quantitation of IgG and albumin in CSF and serum from multiple sclerosis patients by enzyme-linked immunosorbent assay. AB - Immunoglobulin G (IgG) and albumin from unconcentrated cerebrospinal fluid (CSF) and serum of patients with multiple sclerosis (MS) and non-MS controls were quantitated using enzyme-linked immunosorbent assay (ELISA). The IgG levels, IgG/albumin ratios and IgG indexes were significantly increased in CSF of MS patients compared to those of non-MS controls. The method is sensitive, rapid and reproducible and can be applied to routine laboratory use for quantitation of IgG and albumin in unconcentrated CSF from humans as well as in experimental animals used as models for demyelinating diseases. PMID- 3107336 TI - Arthroplasty infections. Antisepsis and asepsis in orthopedics. PMID- 3107337 TI - Ultraclean air and antibiotics for prevention of postoperative infection. A multicenter study of 8,052 joint replacement operations. AB - To determine the value of ultraclean air in operating rooms, 8,052 operations for total hip- or knee-joint replacement were followed up for 1-4 years. For operations done in ultraclean air, bacterial contamination of the wound, deep joint sepsis, and major wound sepsis were substantially less than for operations done in conventionally ventilated rooms. Sepsis was also less frequent when prophylactic antibiotics had been given. The two precautions acted independently so that the incidence of sepsis after operation in ultraclean air and with antibiotics was much less than that when either was used alone. Wound sepsis was associated with an enhanced risk of joint sepsis. Staphylococcus aureus was the commonest joint pathogen, but infections with other organisms, often considered to be of low pathogenicity, were almost as numerous. Most S. aureus infections were traced to sources in the operating room. PMID- 3107338 TI - Ophthalmia neonatorum with special reference to Chlamydia trachomatis. Diagnosis and treatment. PMID- 3107339 TI - Hepatitis-associated aplastic anemia with systemic plasmacytosis. AB - An autopsy case of hepatitis associated aplastic anemia was presented. A 58-year old Japanese female with non-A, non-B hepatitis was admitted on August 2, 1983. Moderate grade of fever and hemorrhagic diathesis appeared on September 16, when hepatitis was evaluated as being under resolving. The peripheral blood and bone marrow findings were consistent with aplastic anemia. Since infection was suggested by increased levels of serum gammaglobulin and CRP, treatment with antibiotics as well as prednisolone and blood transfusion was initiated. Since September 21, gradual tenderness and edema on the right lower abdominal wall appeared. She died on October 3. On postmortem examination, systemic plasmacytosis with lymphadenopathy and septic monilial infection was revealed. Numerous plasma cells were atypical, but were immunohistochemically proved to be polyclonal. The bone marrow showed a massive and diffuse plasma cell proliferation with extremely scarce myeloid cells and megakaryocytes. There was a large granulomatous lesion with monilial infection in the wall of the ileocecum. By these findings, systemic plasmacytosis was suspected to be due to chronic monilial infection. The pathogenesis of systemic plasmacytosis in aplastic anemias and in other diseases were discussed with relation to the present case. PMID- 3107340 TI - An immunohistochemical study on the distribution of glial fibrillary acidic protein, S-100 protein, neuron-specific enolase, and neurofilament in medulloblastomas. AB - In order to clarify the differentiation of medulloblastomas, the authors studied on the morphological features and immunohistochemical expression of glial fibrillary acidic protein (GFAP), S-100 protein, neuron-specific enolase (NSE), and neurofilament (NF) in 31 medulloblastomas. GFAP was detected only in a small number of tumor cells of 5 medulloblastomas; S-100 protein in both small tumor cells and some so-called spongioblastic cells in 16 medulloblastomas; NSE in the more abundant tumor cells and the matrix in 28 medulloblastomas; NF in a few tumor cells of 12 medulloblastomas; GFAP and NF in 2 medulloblastomas, but each of them in different tumor cells. These results suggest that medulloblastomas have a capacity of differentiation along neuronal and/or glial lines. The conventional morphological markers of differentiation in medulloblastomas such as spongioblastic cells and Homer Wright rosettes were not necessarily compatible with expression of immunohistochemical markers such as GFAP or NF. NSE and S-100 protein seem less valuable markers of differentiation because they were detected in both neuronal and glial elements. But NSE, which was observed in most medulloblastomas, might have a value as a marker for medulloblastomas. PMID- 3107341 TI - [Inhibition of aldose reductase from the rat lens by flavonoids]. PMID- 3107342 TI - [Relationship between the efficacy of praziquantel on rabbits infected with Schistosoma japonicum and the immune level of the host]. PMID- 3107343 TI - Irregular chronic stress related selective presynaptic adaptation of dopaminergic system in rat striatum: effects of (-)deprenyl and amitriptyline. AB - Rats were exposed to irregular chronic stress (IRCS, an animal model of depression). Changes in dopamine and serotonin utilization by striata and hippocampi were measured. IRCS did not influence serotonin uptake, serotonin, dopamine, 5-hydroxyindolacetic acid and homovanillic acid levels, while it decreased 3,4-dihydroxyphenylacetic acid level and dopamine uptake. This would reflect selective presynaptic adaptation to IRCS. Neither (-)deprenyl (21 X 0.25 mg/kg, s.c.), nor amitriptyline (21 X X 15 mg/kg, i.p.) could prevent the effects of IRCS. PMID- 3107344 TI - Differences between the effects of two meclofenoxate doses on active training for two-way avoidance in rats. AB - Male Wistar rats were trained for active two-way avoidance in a shuttle-box apparatus for five consecutive days. Meclofenoxate, in doses of 100 and 300 mg/kg i.p., was applied in two separate groups of rats, 60 min before the beginning of the training. Meclofenoxate (Mf), applied in a dose of 100 mg/kg, slightly improved the avoidance training, whereas in a dose of 300 mg/kg it "deteriorated" learning during the last two training days. Retrospective analysis of the experimental results showed that Mf caused a dose-dependent increase in the percentage of rats who were "poor learners", compared with the percentage of "poor learners" among the controls. On the other hand, the Mf-treated "good learners" manifested an essentially better capacity for avoidance training, compared with the control "good learners". The data obtained suggest that Mf increases the adaptational capacities of rats trained for active avoidance possibly in two different ways: in part of the animals it causes improvement of the conditioned reflex activity, in another part of the animals it increases their resistance to the stressogenic stimuli used during such a training. PMID- 3107346 TI - CO2 sensitivity in humans breathing 1 or 2% CO2 in air. AB - Ventilation increases when the concentration of CO2 in the inspired gas is increased, thereby limiting the increase in alveolar and arterial PCO2. The extent of this compensation at low levels of inspired CO2 has been debated. In five healthy humans, we have measured arterial PCO2, arterial pH and ventilation during exposure to 1 and 2% CO2 in the inspired gas. Each exposure lasted at least 7 min and arterial blood was sampled over at least 30 s during the last minute of each period. The ventilation was measured in the sixth and seventh min. The protocol included the sequences: control-test-control and test-control-test with 'test' representing CO2 loading and 'control' 0% CO2, respectively. We found that arterial PCO2 increased and pH decreased at both levels of inspired CO2. The mean increase in arterial PCO2 was 0.09 and 0.25 kPa, at CO2 1 and 2%, respectively. Three subjects were exposed to 1% CO2 in the inspired gas for 28 min flanked by similar control periods. In each period arterial blood samples were taken at 2- or 3-min intervals. Arterial PCO2 remained elevated for at least 20 min during the CO2 loading. The sensitivity to CO2 (ratio of increase in ventilation to increase in arterial PCO2) was within the range described by others at higher levels of inspired CO2. Arterial PCO2 increased by about 10% of the imposed load. We conclude that the increase in ventilation provides only incomplete compensation for exposure to CO2: arterial CO2 is increased and arterial pH decreased also at very low levels of inspired CO2. PMID- 3107345 TI - Free oxygen radicals decrease electrical resistance of microvascular endothelium in brain. AB - The effect of free oxygen radicals on the electrical resistance of brain venular endothelium was studied in anesthetized frogs. The technique allowed continuous recording of the electrical resistance of the vascular wall reflecting its ionic permeability. The oxygen radicals were generated by an enzymatic reaction between xanthine oxidase and hypoxanthine supplied to the surface of the exposed brain. Electrical resistance of the venular endothelium decreased within 1-2 s after the reaction was initiated. Hypoxanthine (1 mM) and xanthine oxidase at a concentration of 10, 25, 50, 100, and 250 mU ml-1 lowered resistance to 1.0, 0.9, 0.8, 0.5 and 0.2 X control value, respectively, within a 3 min period of administration. The effect induced by 25 and 50 mU ml-1 of xanthine oxidase was readily reversible, whereas that induced by the two highest concentrations was irreversible within the observation time. The response was totally blocked by allopurinol as well as by superoxide dismutase plus catalase. Pretreatment with methylprednisolone or BW755C (an inhibitor of cyclo- and lipoxygenase) did not inhibit the response, nor did removal of calcium or magnesium from the extracellular medium. Free oxygen radicals are powerful agents that rapidly induce dynamic changes in the electrical resistance of brain vessels, supporting the notion that they may be important mediators of vascular endothelial damage in the brain. PMID- 3107347 TI - Arterial P CO2 and lung ventilation in man exposed to 1-5% CO2 in the inspired gas. AB - Conflicting results have been published on the shape of the curve relating the change in lung ventilation to the change in alveolar or arterial PCO2 induced by increased inspired CO2 (the CO2 sensitivity). In this study eight human subjects with in-dwelling arterial cannulae were each exposed to five different levels of increased inspired CO2 (1-5%). Arterial PCO2 and ventilation were measured in the 7th minute of each period of CO2 exposure. Each CO2 exposure period was flanked by control periods in which similar measurements were carried out during air breathing. We found non-linear increases in both ventilation and arterial PCO2 with increasing levels of inspired CO2. When 5% CO2 in air was inspired the arterial PCO2 increased by about 15% of the inspired CO2 load. There was no significant non-linearity in the relation between change in alveolar ventilation (normalized to body surface) and change in arterial PCO2. The inter-individual variation in CO2 sensitivity was less when alveolar ventilation was normalized to the CO2 output rather than to body surface area. We conclude that the sensitivity to CO2 is close to constant within the range 0-5% CO2 in the inspired gas. PMID- 3107349 TI - Spinal cord electrophysiological activities after small doses of TRH in control subjects and ALS patients. PMID- 3107350 TI - First results with percutaneous endoscopic gastrostomy. PMID- 3107348 TI - Cisternal and lumbar CSF levels of arachidonate metabolites after subarachnoid haemorrhage: an assessment of the biochemical hypothesis of vasospasm. AB - Several naturally occurring compounds have been identified in human cerebrospinal fluid (CSF) after subarachnoid haemorrhage (SAH) as possible vasoactive agents involved in the biochemical mechanism of vasospasm. The authors have measured, in 30 patients admitted for SAH, CSF concentrations of two arachidonic acid metabolites. Prostacyclin and Prostaglandin D2, as representative of vasodilator and vasoconstrictor compounds. CSF samples were made available by lumbar punctures and intraoperative cisternal punctures. Nine patients presented with symptomatic vasospasm: lumbar CSF Prostaglandin D2 levels are significantly higher than in patients without vasospasm. The Cisternal Prostaglandin D2 level is significantly higher than the lumbar CSF concentration; CSF Prostacyclin levels do not significantly differ in the two groups of patients. These data suggest the presence of an imbalanced biochemical situation responsible for promoting vasospasm. The evaluation of cisternal levels of arachidonate metabolites support the hypothesis of the clotting phenomenon around the ruptured aneurysm wall as an important predictive pattern of vasospasm onset after SAH, as shown in computed tomography. PMID- 3107351 TI - Proteases, their inhibitors and the extracellular matrix: factors in nerve-muscle development and maintenance. PMID- 3107352 TI - Therapeutic trial of intrathecal thyrotropin-releasing hormone (TRH) and a TRH analogue in amyotrophic lateral sclerosis (ALS). PMID- 3107353 TI - Hospital nutrition in geriatric long-term care medicine: II. Effects of dietary supplements. AB - The effects of three different dietary supplements were studied in 28 women admitted to geriatric long-term care by recording the dietary intake, anthropometric variables and selected biochemical analyses before and during an 8 week experimental period. The validity of the dietary intake measurements was investigated and judged as acceptable. Before supplementation the mean daily intake of energy was 5.2 MJ/1247 kcal and vitamin D and thiamine were the nutrients most commonly deficient. One third of the patients had low dietary intake of vitamin A. The intake of ascorbic acid, riboflavine and calcium were appropriate. The mean values of haemoglobin, serum albumin, plasma prealbumin and transferrin were within reference limits despite the fact that a quarter of the patients had signs of inflammation. The dietary intake improved significantly during the experimental period in all three groups and the intake of energy increased by 25%. A gain of weight was noted in all groups. The level of serum retinol-binding protein increased in two of the groups. The suppression of the appetite due to supplementation was low and the intake of snacks decreased from 20% to 11% of the energy intake. PMID- 3107354 TI - Pharmacologic characterization of the antiinflammatory properties of a new dual inhibitor of lipoxygenase and cyclooxygenase. AB - SK&F 86002 [6-(4-fluorophenyl)2,3-dihydro-5-(4-pyridinyl)imidazo (2,1 b)thiazole], a dual inhibitor of arachidonic acid metabolism, administered orally to rats prevented the development of carrageenan-induced edema, immune- and nonimmune-mediated inflammation of adjuvant-induced arthritis (AA) and reduced established inflammation in AA and collagen type II-induced arthritis. A similar profile of activity was observed following treatment with the cyclooxygenase inhibitor, indomethacin. However, unlike other nonsteroidal antiinflammatory drugs, SK&F 86002 exhibited antiinflammatory activity in inflammation models that are insensitive to cyclooxygenase inhibitors such as the established inflammation in carrageenan-induced edema and the edema induced by arachidonic acid and platelet activating factor. Moreover, SK&F 86002, but not indomethacin, inhibited the immune-mediated inflammatory responses evoked in sensitized animals by challenge with purified protein derivative. In addition, SK&F 86002 produced dose related analgesia in mice, which was not reversed by the narcotic antagonist, naltexone. SK&F 86002 thus represents an orally active antiarthritic and analgesic compound with novel antiinflammatory properties. PMID- 3107355 TI - [Manifestation of mictional disturbance in four cases of von Recklinghausen's disease]. AB - Four patients with neurofibromatosis (von Recklinghausen's disease) manifesting mictional disturbance are presented. They were a man aged 41 years (A) and 3 women aged 26 (B), 46 (C) and 32 (D) years, and their chief complaints included urinary retention, dysuria, urinary frequency and urinary retention. None of them had any organic obstructive disorders in the lower urinary tract. Case A who had neurofibroma at the C2 and L1-2 vertebral bodies had inactive bladder and his urinary flow rate was less than 10 ml/sec. In case B, cystometrogram was initially normal, but changed to inactive bladder type one year later and neurofibromas were found in the vertebral bodies of Th7-8 and L2. Case C, who had inactive bladder cystometrically, underwent removal of 1-acoustic neurinoma and neurinomas of cauda equina. Case D had hyperactive bladder and received resection of the neurofibroma of vertebral bodies from C6 to Th4. The finding of cystometrogram and type of urinary miction disorders suggested vertebral neurofibroma at an early stage. PMID- 3107356 TI - [Studies on the usefulness of a long-term, high-dose treatment of methylcobalamin in patients with oligozoospermia]. AB - Methylcobalamin (CH3-B12) was administrated in a dose of 6 mg per day (group A, 16 cases) or 12 mg per day (group B, 23 cases) for 16 weeks to patients with oligozoospermia. There was no difference between group A and group B regarding vitamin B12 concentrations in the serum or seminal fluid. CH3-B12 appeared to be transported to seminal fluid very efficiently. However, results from group A and group B did not differ with respect to this parameter. The efficacy rate for group A was 37.5% and that for group B was 39.1%. From these results, it was concluded that a long-term, high dose treatment of CH3-B12 was useful for the treatment of patients with oligozoospermia. Since the efficacy rates were not different between the two groups, 6 mg per day would be the recommended dose. Clinical adverse reactions were observed in one patient in each group. Drug related laboratory adverse reactions were observed in only one patient in group B. PMID- 3107357 TI - Inhibition of N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder tumor in rats by alpha-difluoromethylornithine. AB - The therapeutic effects of alpha-difluoromethylornithine (DFMO) on rats with bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) were examined. Eight-week-old male Wistar rats were given 0.05% BBN in their drinking water for a period of 4 weeks. Therapy (0.1% DFMO in their drinking water) was started at week 4 and all rats were killed at week 60. DFMO was seen to significantly reduce the incidence, the mean number and the total size of tumors. No side-effects of DFMO were noted, except alopecia, which started at month 7 of the therapy. PMID- 3107358 TI - [Combined administration of human chorionic gonadotropin and human menopausal gonadotropin in idiopathic male infertility]. AB - Clinical experiences of HCG-HMG therapy for 56 cases of idiopathic male infertility were studied. Serum levels of LH, FSH and testosterone were measured before therapy. Sperm density improved in 25% of all cases. In the low FSH group, sperm density showed a high rate of improvement. The basal FSH was the best indicator to predict the prognosis of fertility. Additional measurements of LH and FSH response to GnRH gave further information on the prospect of fertility. PMID- 3107359 TI - Penile magnification pharmacoarteriography: details of intrapenile arterial anatomy. AB - To establish a base of normality against which state-of-the-art penile arteriograms can be assessed, we analyzed selective magnification penile pharmacoarteriograms from 23 men who were not believed to have arteriogenic impotence. The penile arteries showed no evidence of acquired obstructive disease, and all individuals had had normal sexual function in the recent past. The vascular patterns were highly variable and frequently differed from classic descriptions found in textbooks of anatomy. Normal variations that could be easily confused with arterial obstruction were unilateral origin of all cavernosal branches, unilateral hypoplasia of a dorsal penile artery, and aberrant origin of bulbar or cavernosal arteries. Multiple potential collateral routes were shown, including transverse collaterals at the root of the penis and communications between cavernosal and dorsal penile arteries. Appreciation of the type and frequency of anatomic variants and potential collateral routes is important in correctly interpreting penile angiograms and in evaluating the hemodynamic significance of suspected stenoses. PMID- 3107360 TI - Osteomyelitis complicating fracture: pitfalls of 111In leukocyte scintigraphy. AB - 111In-labeled leukocyte imaging has shown greater accuracy and specificity than alternative noninvasive methods in the detection of uncomplicated osteomyelitis. Forty patients with suspected osteomyelitis complicating fractures (with and without surgical intervention) were evaluated with 111In-labeled leukocytes. All five patients with intense focal uptake, but only one of 13 with no uptake, had active osteomyelitis. However, mild to moderate 111In leukocyte uptake, observed in 22 cases, indicated the presence of osteomyelitis in only four of these; the other false-positive results were observed in noninfected callus formation, heterotopic bone formation, myositis ossificans, and sickle-cell disease. These results suggest that 111In-labeled leukocyte imaging is useful for the evaluation of suspected osteomyelitis complicating fracture but must be used in conjunction with clinical and radiographic correlation to avoid false-positive results. PMID- 3107361 TI - Evaluation of ectopic bone by CT. AB - The CT appearance of ectopic bone and its maturation in 25 patients were correlated with the findings on radiographs and bone scans. Ossification progressed from an early appearance of soft-tissue density of lower attenuation than muscle to a calcific density paralleling radiographic and scintigraphic evidence of bone formation. Persistent unossified, low-density soft tissue was detected adjacent to mineralized areas of ectopic bone in 14 patients up to 16 years after neurologic injury, often with bone-scan evidence of maturity of the ectopic bone. This soft tissue most likely corresponds to immature, unossified connective tissue, which may have a potential for ossification. Detection of areas of soft-tissue density by CT and their avoidance during surgical resection of an ankylosing mass of ectopic bone may reduce intraoperative hemorrhage and postoperative ectopic bone recurrence. PMID- 3107363 TI - Evidence for dermal absorption as the major route of body entry during exposure of transformer maintenance and repairmen to PCBs. AB - Traditional industrial hygiene assessment of exposure to polychlorinated biphenyls (PCBs) has long focused on air concentrations as a surrogate measure of worker dose. Evidence is presented to support the hypothesis that the dermal and dermal/oral routes of worker PCB exposure are major contributors to total PCB body burden in the group of transformer maintenance and repair personnel studied. Additional evidence is presented to demonstrate the critical role of work practices in determining PCB exposure. These hypotheses challenge the long-held notion of the pre-eminent importance of respiratory exposure to PCBs. PMID- 3107362 TI - Occurrence of exercise-induced and spontaneous wide complex tachycardia during therapy with flecainide for complex ventricular arrhythmias: a probable proarrhythmic effect. AB - Flecainide acetate, a new antiarrhythmic agent, possesses favorable pharmacokinetic and hemodynamic properties and demonstrates highly favorable antiarrhythmic activity in patients with ventricular arrhythmias. However, the proarrhythmic potential of flecainide deserves further evaluation. In 7 (13%) of 55 consecutive patients treated with oral flecainide, 200 to 600 mg/day, for complex ventricular arrhythmias (including sustained ventricular tachycardia in 14), we observed the appearance of new or more sustained exercise-induced (five patients) or spontaneous (two patients) wide complex tachycardia. The mechanism of wide complex tachycardia appeared to be ventricular tachycardia in all seven. In our series, episodes were self-remitting or successfully treated. In four patients, wide complex tachycardia did not recur during exercise testing during alternative antiarrhythmic therapy (three patients) or no antiarrhythmic therapy (one patient). These observations raise the possibility of flecainide-related proarrhythmia, manifested as an increased propensity to exercise (activity) induced wide complex tachycardia, which was not reliably predicted by results of Holter recordings or programmed electrical stimulation. Patients with complex ventricular arrhythmias beginning long-term treatment with oral flecainide should be considered for treadmill exercise testing together with ambulatory monitoring as part of the initial assessment of drug efficacy. PMID- 3107364 TI - Risk factors for the development of proarrhythmic events. AB - Definitions of proarrhythmia, including clinical consequence, were applied to the flecainide and encainide data bases to determine risk factors for serious proarrhythmic events or deaths. Such outcomes with flecainide were far less common for patients with benign or potentially lethal ventricular arrhythmias compared to patients with predominantly lethal ventricular arrhythmias. No deaths from proarrhythmia during flecainide therapy occurred in patients without structural heart disease. Serious proarrhythmic events and deaths were more common in patients in whom therapy was initiated in hospital than in those in whom therapy was initiated out of hospital. When the flecainide dosage for patients with lethal ventricular arrhythmias was chosen using steady-state pharmacologic principles, the occurrence of all proarrhythmic events and deaths dropped from 26% and 13% to 10% and 0%, respectively. Structural heart disease, sustained ventricular tachycardia, inpatient initiation and large-dose escalation of class IC drugs are the primary risk factors for development of proarrhythmic events. PMID- 3107365 TI - Ten-year effect of medical and surgical therapy on quality of life: Veterans Administration Cooperative Study of Coronary Artery Surgery. AB - The long-term effect of medical vs surgical therapy on quality of life was evaluated by New York Heart Association functional classification, severity of angina and exercise performance in 427 surviving patients with stable angina at 10 years. Surgically assigned patients had significantly more improvement in functional classification, relief of angina and exercise performance at 1 and 5 years than medically assigned patients. Relative to entry, functional classification was improved in 65% of surgically treated patients at 1 year and in 51% at 5 years, compared with 45% and 40%, respectively, of medically treated patients. Marked improvement in angina was observed in 49% of surgical patients at 1 year and in 41% at 5 years, vs 12% and 17%, respectively, in medical patients. At 10 years, quality of life was not significantly different in the 2 treatment groups: 52% of surgical patients had an improved functional classification, compared with 46% of medical patients, while 33% of surgical and 37% of medical patients had a marked improvement in angina. Exclusion of medical and surgical nonadherers had little effect on the 1- and 5-year comparisons. The 10-year treatment differences, however, were accentuated when 123 medically assigned patients who later underwent operation and who benefited from it were excluded from the analysis. In surgical patients, a strong association was observed between graft patency and functional class at 1 year, but not at 5 and 10 years. In general, patients with some or all grafts open had more improvement in functional classification than patients with all grafts closed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107366 TI - Need for better severity indexes of acute myocardial infarction under diagnosis related groups. AB - Clinical, demographic and administrative data, including length of stay and institutional charges, were examined for 219 patients hospitalized for acute myocardial infarction (AMI). Neither length of stay nor charges differed among AMI patients with or without cardiovascular complications as defined by Medicare's diagnosis-related group (DRG) categories (DRG 121 and 122, respectively) for patients who are discharged alive. Myocardial enzyme peak levels are the best predictors of hospital resource consumption for patients with AMI when considered alone or in combination with other factors. The "cardiovascular complications" designated by discharge diagnoses did not reflect resource consumption in our patient population. Sixteen percent of the patients studied underwent cardiac catheterization during hospitalization. These patients stayed in the hospital longer and incurred 70% higher charges; nevertheless, they were grouped with the remaining AMI patients in the current DRG formulation. Clinical evaluations such as cardiovascular complications are subject to interpretation, and are therefore less credible than enzyme measurements for recognizing the severity of a patient's AMI. Reimbursement based on objective measurements may avoid payment inequities. PMID- 3107367 TI - Tissue plasminogen activator activity and inhibition in acute myocardial infarction and angiographically normal coronary arteries. AB - Parameters of blood coagulation, blood platelet reactivity and fibrinolysis were analyzed in 18 patients with acute myocardial infarction (AMI) and angiographically normal coronary arteries. This study group was compared with a patient control group of 18 AMI patients with 1-vessel obstructive coronary artery disease. Patients were matched for sex, age and AMI date. A healthy control group consisted of 18 sex- and age-matched volunteers. Blood coagulation measurements and platelet reactivity were similar in the 3 groups, except for fibrinogen, which was significantly higher in the patient control group. Plasma activity of tissue plasminogen activator (tPA) was detectable in only 2 patients in the study group, 9 in the patient control group (p less than 0.02) and 12 in the healthy control group (p less than 0.0001). Median plasma tPA inhibitory activity was higher in the study group (10.3 IU/ml) and the patient control group (8.1 IU/ml) than in the healthy control group (2.7 IU/ml, p less than 0.0001 and p less than 0.03). Thus, reduced activity and enhanced inhibition of plasma tPA may be important factors in the origin of coronary thrombosis, especially in the absence of coronary artery disease. PMID- 3107368 TI - A metabolic comparison of a pure long-chain triglyceride lipid emulsion (LCT) and various medium-chain triglyceride (MCT)-LCT combination emulsions in dogs. AB - Two 20% lipid emulsions containing mixtures of long-(LCT) and medium-chain triglycerides (MCT) were compared with a 20% LCT lipid emulsion. Beagles were infused with emulsions containing either 100% LCT, 75% LCT-25% MCT, or 50% LCT 50% MCT. The emulsions were part of a total parenteral nutrition (TPN) regimen that included 10% dextrose and 5.5% amino acids. Basic nutritional parameters as well as elimination kinetics were monitored. Plasma linoleic acid, ketone, lactate, pyruvate, insulin, glucose, and carnitine were analyzed. The 75% LCT-25% MCT emulsion offers little advantage over 100% LCT as a metabolic substrate. The 50% LCT-50% MCT combination proved to be a potentially better caloric source due to rapid elimination kinetics, increased ketone production, lack of deposition, and no interference with linoleic acid metabolism. PMID- 3107369 TI - Conservative treatments for obesity. PMID- 3107370 TI - Acquired von Willebrand disease due to inhibitor of human myeloma protein specific for von Willebrand factor. AB - A patient with acquired von Willebrand disease associated with multiple myeloma (IgG-lambda) is described. Mixture of his plasma or IgG fraction with washed control platelets resulted in the inhibition of aggregation with ristocetin, but mixture of control plasma or IgG fraction with washed patient platelets showed no inhibition of ristocetin-induced aggregation. Although his vWF: Ag, RCo, and factor VIII coagulant activity were all normal, inactivation of RCo was induced in normal plasma by incubation with patient plasma. Crossed immunoelectrophoretic analysis showed that vWF:Ag was composed of much more anodic component. A marked increase of Factor VIII and a rapid return of RCo to the baseline after 1-deamino 8-arginine vasopressin (DDAVP) infusion were observed. A transient increase in vWF:Ag after the infusion of DDAVP showed with less anodic forms and in the relative proportion as in normal. Treatment of the underlying disease also led to a correction of the bleeding time, improvement of platelet adhesion and ristocetin-induced aggregation, and normalization of crossed immunoelectrophoresis of vWF:Ag. The present study showed that myeloma-associated IgG interacted specifically with the antigenic sites on the von Willebrand portion of the Factor VIII complex. PMID- 3107371 TI - Ileocolonic schistosomiasis presenting as lymphoma. AB - The blood flukes of the genus Schistosome have a wide geographic distribution. Schistosoma japonicum is found in the Far East while Schistosoma mansoni is found in Africa, South America, the Middle East, and the Carribean. There are numerous other species of Schistosome; however, japonicum, mansoni, and hematobium account for the majority of human disease. Infection of the gastrointestinal tract is not uncommon in the United States. Recognition of this disease is important for appropriate medical therapy and avoidance of unnecessary surgery. A case of schistosomiasis simulating small bowel lymphoma is presented and salient features of this infection are reviewed. PMID- 3107372 TI - Penicillin VK-induced esophageal ulcerations. PMID- 3107373 TI - Gastric plasmacytoma: an early lesion diagnosed with the aid of immunoperoxidase and immunogold techniques. AB - A case of gastric plasmacytoma in a 34-yr-old woman has been presented. The demonstration of monotypic intracytoplasmic immunoglobulin of IgM-kappa type in biopsy specimens by immunoperoxidase technique contributed the confident histological diagnosis. In the resected stomach, IgM-kappa monoclonal proliferation of plasmacytic tumor cell was also demonstrated in the lamina propria and in the perivascular space of the submucosa, which was distinct from plasma cells of polyclonal nature diffusely infiltrating in the adjacent mucosa. The double immunogold staining confirmed the presence of immunoglobulin IgM-kappa type in the distended rough endoplasmic reticulum of the tumor cell. PMID- 3107374 TI - Correction of the bleeding time in treated patients with severe von Willebrand disease is not solely dependent on the normal multimeric structure of plasma von Willebrand factor. AB - Even though it is generally held that cryoprecipitate and fraction I-O correct the prolonged bleeding time (BT) in patients with von Willebrand disease (VWD), perusal of reported data indicates that the correction is usually short-lasting and often partial. We decided to do a controlled study of the relationship between the multimeric structure of von Willebrand factor (VWF) and the BT in five patients with severe (type III) VWD after infusion of three plasma concentrates ("wet" cryoprecipitate, lyophilized cryoprecipitate, and fraction I O) given in random order. The dosage of concentrates was tailored from in vitro measurements to achieve post-infusion levels of ristocetin cofactor above the lower normal limit (50 U/dL) for at least 3 hours. The postinfusion BT became transiently normal in only two of five patients treated with wet cryoprecipitate, whereas it remained prolonged in all five patients treated with lyophilized cryoprecipitate or fraction I-O. For all the concentrates, the proportion of large VWF multimers calculated by scanning the electrophoretic gels were the same as those for normal standard plasmas. An intact multimeric structure was recovered in postinfusion plasmas of patients treated with wet cryoprecipitate, whereas there was a postinfusion loss of large multimers after lyophilized cryoprecipitate and fraction I-O. These findings indicate that the attainment of a normal BT is the exception rather than the rule after the infusion of three plasma fractions used in the treatment of severe VWD, and that an intact multimeric structure in concentrates and postinfusion plasmas is necessary but not sufficient to sustain a normal BT. PMID- 3107375 TI - Pregnancy in lupus nephritis and related disorders. AB - We studied retrospectively the influence of lupus nephropathy on the outcome of pregnancy and of pregnancy on the course of lupus nephritis in 213 pregnancies observed from 1962 to 1985 in a series of 73 patients with systemic lupus erythematosus (SLE). Renal biopsy demonstrated diffuse or focal proliferative glomerular lesions in 48 of 66 patients. The overall incidence of live births was 162 in 213 (76%). Fetal death rate, corrected for induced abortions, was markedly higher when SLE first manifested during or immediately after the index gestation (five of 11, or 45%) than in pregnancies that began prior to clinical onset of SLE (16 of 140, or 11.4%) and in those occurring after onset of SLE (five of 38, or 13.1%). Relapse or an exacerbation of SLE activity occurred in 18 (34%) of 53 pregnancies (in 35 women) which took place after the clinical onset of the disease. Such complications were more frequent (16 of 26 cases, or 61%) in pregnancies in which SLE was clinically active at conception as compared with gestations in which SLE was in clinical remission prior to conception (two of 27 cases, or 7%). There were six instances of severe renal "flare-up," four of which progressed to end-stage renal failure (ESRF) within a few years, including one instance in a patient who was in remission before conception. We conclude that successful outcome of pregnancy without deterioration of maternal renal function may most often be obtained even in previously severe forms of SLE, provided gestation is started in a period of sustained therapeutic remission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107376 TI - The donor's decision in renal transplantation: a cost-benefit analysis. AB - We previously suggested that a fully informed competent potential donor be allowed to donate his/her kidney as long as society will not suffer from the proposed transplant, even if there is added risk for the donor. To help make this sometimes difficult determination, we have constructed a benefit equation that calculates the benefit to society (either positive or negative) of any proposed living-related transplant. We believe that as long as the benefit calculated is positive, the prospective donor should generally be allowed to donate his kidney, since society will not be injured. It is emphasized that the benefit equation should be viewed as a guide to be used in difficult situations where the donor may be at added risk of renal death, and is not meant to supplant the entire complex decision-making process regarding living-related kidney donation. PMID- 3107377 TI - Psychogenic polydipsia with hyponatremia: report of eleven cases. AB - Psychogenic polydipsia is an uncommon clinical disorder characterized by excessive water-drinking in the absence of a physiologic stimulus to drink. The excessive water-drinking is well tolerated unless hyponatremia supervenes. This report describes 11 patients with psychogenic polydipsia and hyponatremia (ten men and one woman) who were collectively hospitalized a total of 70 times for treatment of complications of this disorder. This group differs from the classical patient with psychogenic polydipsia, ie, a hospitalized schizophrenic, in that none was institutionalized and there was a high incidence of chronic alcoholism (10), intractable hiccups (7), self-induced vomiting (6), and laboratory evidence for rhabdomyolysis (5). PMID- 3107379 TI - Activity of ciprofloxacin and other fluorinated quinolones against mycobacteria. AB - The new fluorinated quinolones display interesting but variable activity against mycobacteria. Almost all compounds tested (ciprofloxacin, ofloxacin, enoxacin, norfloxacin, difloxacin, CI-934, A-56620, and megalone) inhibit Mycobacterium tuberculosis at achievable serum concentrations, with ciprofloxacin and ofloxacin most active by weight (minimal inhibitory concentration at which growth of 90 percent of strains is inhibited is equal to 1 microgram/ml or less). The growth of Mycobacterium kansasii, Mycobacterium xenopi, and Mycobacterium fortuitum is also well inhibited by these agents in the same range of concentrations. Activity against the Mycobacterium avium complex is method-dependent, with growth of perhaps one third of the strains isolated from patients with the acquired immune deficiency syndrome inhibited by ciprofloxacin. Determination of individual drug efficacy data in experimental mycobacterial infections is not a practical goal. However, combination therapy studies are in progress using murine models of both M. tuberculosis and M. avium challenges. Ofloxacin has been used with some success in human patients with pulmonary tuberculosis. Oral administration may be an important advantage, and, when used in combination with other active agents, the new quinolones may have a useful role in treating mycobacterial infections. PMID- 3107378 TI - Long-term comparisons of citrate and heparin as anticoagulants for hemodialysis. AB - Citrate was compared to heparin as an anticoagulant during chronic hemodialysis. A randomized crossover design was used in six stable male dialysis patients. There were no measurable crossover effects. Use of citrate as the sole anticoagulant for periods of 2 months was easily accomplished, free of complications, and resulted in comparable clearance of solutes. Major laboratory parameters were similar with both anticoagulants. Importantly, there was no significant citrate accumulation. The results also indicate that recurrent use of heparin during dialysis has no measurable effect on lipid metabolism in stable patients. PMID- 3107380 TI - Evaluation of ciprofloxacin's synergism with other agents by multiple in vitro methods. AB - The efficacies of ciprofloxacin, ceftizoxime, azlocillin, mezlocillin, and amikacin (minimal inhibitory concentration and minimal bactericidal concentration) against six Pseudomonas aeruginosa, six Enterobacteriaceae, and six group D streptococcal strains were evaluated using both agar and broth susceptibility methods, two inoculum sizes (5.7 log10 colony-forming units (cfu)/ml and 7.7 log10 cfu/ml), and aerobic and anaerobic incubation conditions. The results showed agreement between broth and agar methods of susceptibility determination; inoculum effects with beta-lactam antimicrobials; and decreased susceptibility to amikacin under anaerobiasis. Ciprofloxacin combined with azlocillin, ceftizoxime, or aminoglycosides in broth microdilution checkerboards against 100 gram-negative bacilli and gram-positive cocci demonstrated that ciprofloxacin combined with azlocillin or ceftizoxime was synergistic against at least 50 percent of P. aeruginosa and Serratia marcescens isolates and that ciprofloxacin combined with amikacin was synergistic against at least 50 percent of S. marcescens and Staphylococcus aureus isolates. Ciprofloxacin and azlocillin in combination were evaluated by microdilution checkerboard, agar dilution, and broth macrodilution time-kill methods at two inoculum sizes to assess antibacterial activity. Comparison between in vitro combination methods showed the following: the presence or absence of checkerboard synergism (as defined by the fractional inhibitory concentration index and the fractional bactericidal concentration index) with ciprofloxacin and azlocillin did not correlate with time-kill results; and good agreement between methods when comparing broth macrodilution time-kill (3 log10 cfu/ml or more decrease) with antimicrobial combinations at a single concentration in both agar and microdilution broth for ciprofloxacin and azlocillin. Rabbit studies using subcutaneous dialysis membrane chambers inoculated with six P. aeruginosa, six Enterobacteriaceae, and six group D streptococcal strains were performed using ciprofloxacin, azlocillin, ceftizoxime, and amikacin alone and in combination as therapy. In vitro testing of antibiotic combinations that provided the best prediction of in vivo outcome were combination antibacterial activity (3 log10 cfu/ml or more decrease) at 24 hours using either broth macrodilution time-kill or antimicrobial combinations at a single concentration in either agar or broth (microdilution). For the most efficacious in vivo combination, ciprofloxacin plus azlocillin, there was in vitro correlation with in vivo outcome for 17 of 18 isolates. PMID- 3107381 TI - Efficacy of ciprofloxacin in stationary-phase bacteria in vivo. AB - The granuloma pouch model in mice infected with Escherichia coli or Pseudomonas aeruginosa was used to investigate the bactericidal effect of ciprofloxacin in vivo on bacteria in the stationary growth phase. Ciprofloxacin caused a rapid decline in the number of colony-forming units (cfu) of E. coli shortly after initiation of therapy (40 mg/kg, intraperitoneally). Ciprofloxacin was more effective than norfloxacin or pefloxacin and comparable in efficacy to ofloxacin. The drugs penetrated well into the pouch exudate, exceeding the minimal inhibitory concentrations (MICs) of the infecting organisms. The concentrations of pefloxacin or ofloxacin were higher than those of norfloxacin or ciprofloxacin. Ciprofloxacin also showed good killing effects in pouches infected with one strain of P. aeruginosa (ICB 7453, MIC of 0.06 micrograms/ml). However, with another P. aeruginosa strain (ICB 7933), which has a MIC of 0.5 micrograms/ml, killing of stationary cells in vivo was not very pronounced. Electron microscopic evaluation of the pouch exudate revealed that phagocytosed and non-phagocytosed E. coli cells were severely damaged in comparison with untreated control cells. The earliest ultrastructural changes could be observed 15 minutes after initiation of therapy. The results demonstrate that ciprofloxacin is effective in mice for the treatment of a local inflammatory abscess harboring a stationary population of E. coli or P. aeruginosa. This specific kind of killing occurs in vivo when drug concentrations are at least eight to 10 times higher than the MIC. PMID- 3107382 TI - Light chain cast nephropathy and acute renal failure associated with rifampin therapy. Renal disease akin to myeloma kidney. AB - Acute renal failure developed in a patient with a normal serum creatinine level, after treatment with rifampin was begun for tuberculosis. Renal biopsy revealed an obstructive nephropathy due to tubular casts. Immunoperoxidase and immunofluorescence studies demonstrated the presence of heterogeneous light chains within these casts. This unique drug-induced renal disease is discussed with reference to the literature and to possible analogies with myeloma kidney. PMID- 3107383 TI - Catheter-related sepsis: pathogenesis and treatment. PMID- 3107384 TI - Prevention of venous thromboembolism after general surgery. Cost-effectiveness analysis of alternative approaches to prophylaxis. AB - A number of methods of prophylaxis can reduce the risk of postoperative venous thromboembolism in patients undergoing general surgery. The cost-effectiveness of several of these--low-dose subcutaneous heparin, intermittent pneumatic compression, graduated compression stockings, heparin plus dihydroergotamine, heparin plus stockings, and intermittent pneumatic compression plus stockings- was assessed by pooling data from published reports of randomized controlled trials. Using clinical protocols, costs for prophylaxis, diagnosis, and treatment of venous thromboembolism were determined. The expected outcomes and costs of each strategy were then calculated using techniques of decision analysis. The results indicate that stockings are the only prophylactic method that is actually cost-saving. Costs of care average $34 less per admission for patients using stockings than for those receiving no prophylaxis. Most other methods of prophylaxis further reduce thromboembolic risk, but increase costs by $50 to $88 per patient relative to costs for the use of stockings. Differences in the cost effectiveness of these prophylaxis are more marked, ranging from about $50,000 to almost $500,000 per additional life saved. PMID- 3107385 TI - American trypanosomiasis (Chagas' disease) in Central American immigrants. AB - A survey was conducted to determine the prevalence of infection with Trypanosoma cruzi, the protozoan etiologic agent of American trypanosomiasis (Chagas' disease), among Nicaraguan and Salvadoran immigrants living in the Washington, D.C., area. The serum samples of study subjects were tested for reactivity with T. cruzi antigens in an enzyme-linked immunosorbent assay, and also tested for antibody specific for the 72 and 90 kilodalton (kDa) surface glycoproteins of the parasite in an immunoprecipitation and electrophoresis procedure. Xenodiagnosis using reduviid bugs to detect parasites, and clinical evaluations for cardiac and gastrointestinal disease were performed in patients in whom results of both serologic tests were positive. Of 205 subjects studied, 4.9 percent were infected with T. cruzi, and parasites were isolated from 50 percent of those in whom xenodiagnosis was attempted. No significant cardiac or gastrointestinal abnormalities were detected in the six infected patients who were evaluated clinically. These findings suggest that a sizable proportion of persons in this immigrant group are infected with this organism. Thus, routine serologic testing for antibody to T. cruzi may be warranted in immigrants from these countries, especially in view of the potentially serious consequences of infection with this parasite, and also because of the risk of transmission of T. cruzi by blood transfusion. PMID- 3107386 TI - Thrombolytic therapy for MI. PMID- 3107387 TI - The ovarian renin-angiotensin system: renin-like activity and angiotensin II/III immunoreactivity in gonadotropin-stimulated and unstimulated human follicular fluid. AB - Renin-like activity and angiotensin II/III immunoreactivity in follicular fluids from 34 women stimulated with human menopausal gonadotropin and human chorionic gonadotropin (56.8 +/- 6.5 ng angiotensin I per milliliter per hour and 187 +/- 21 pg/ml [mean +/- SEM], respectively) were much higher (p less than 0.001) than in follicular fluids from 12 unstimulated preovulatory women (1.41 +/- 0.37 ng angiotensin I per milliliter per hour and 58.5 +/- 13.7 pg/ml) and in simultaneously drawn plasma (4.47 +/- 0.73 ng angiotensin I per milliliter per hour and 31.8 +/- 11.6 pg/ml, respectively; p less than 0.001). Plasma renin-like activity and angiotensin II/III immunoreactivity in stimulated cycles did not differ from unstimulated cycles. Follicular fluid angiotensin II/III immunoreactivity correlated significantly with follicular fluid renin-like activity in stimulated (r = 0.72; p less than 0.01) and in unstimulated samples (r = 0.86; p less than 0.01). Significant correlation was found also between follicular fluid renin-like activity and estradiol. A sharp preovulatory rise of renin-like activity and angiotensin II/III immunoreactivity was noted in unstimulated follicular fluid samples collected on cycle days 13 and 14 compared to days 9 through 12 (p less than 0.01). The findings that follicular fluid renin like activity and angiotensin II/III immunoreactivity are correlated, and that gonadotropins have a stimulatory effect on follicular fluid concentrations support our concept of a physiologic intrinsic ovarian renin-angiotensin system. PMID- 3107388 TI - Chlamydia trachomatis infection and pregnancy outcome. AB - Chlamydia trachomatis is now recognized as the most common sexually transmitted disease organism in the United States. Although the potential for vertical transmission of C. trachomatis from pregnant women to their infants is well established, the extent to which infection adversely affects pregnancy and causes perinatal complications remains controversial. We report herein the results of a prospective study of 270 pregnant women with endocervical C. trachomatis compared with 270 matched control subjects (age +/- 1 year, race, and socioeconomic status). Among the entire group (n = 540), the rates of pregnancy complications were: premature rupture of the membranes, 54/270 (10%); preterm delivery, 55 (11%); amnionitis, 20 (4%); intrapartum fever, 23 (4.3%); small for gestational age, 76 (14.5%); postpartum endometritis, 31 (6%); and neonatal sepsis, 10 (1.8%). No statistically significant differences were noted between cases and controls for any of these variables. In the subset of women with recent or invasive chlamydial infection, indicated by the presence of IgM antibody against C. trachomatis, preterm delivery occurred in 13/67 IgM-positive versus 8/99 IgM negative (p = 0.03) cases. Premature rupture of the membranes was present in 13/67 IgM-positive versus 8/99 IgM-negative (p = 0.03). PMID- 3107389 TI - Chlamydia trachomatis infection among patients undergoing chorionic villus sampling. AB - Chlamydia trachomatis was recovered from the cervices of 0.5% (3/560) of women undergoing chorionic villus sampling. Because this population has been identified as a low-risk group, routine screening of sexually transmitted Chlamydia prior to chorionic villus sampling is not warranted. PMID- 3107390 TI - Effects of plasma on the platelet antiaggregatory action of prostacyclin in pregnancy. AB - Platelet-poor plasma from 13 nonpregnant, 33 normally pregnant, and eight preeclamptic women was incubated with prostacyclin. The ability of platelet-poor plasma to diminish the antiaggregatory effect of prostacyclin was assessed by measuring this effect on arachidonic acid-induced platelet aggregation. Platelet aggregation greater than 95% in response to arachidonic acid was observed when incubated plasma without exogenous prostacyclin was assayed. When prostacyclin and platelet-poor plasma were preincubated together, subsequent arachidonic acid induced platelet aggregation measured 9.6% in samples from nonpregnant patients, 40.3% in samples from normally pregnant patients, and 78.2% in samples from patients with preeclampsia. The ability of exogenous prostacyclin to inhibit arachidonic acid-induced platelet aggregation was significantly different in the presence of plasma from nonpregnant, normally pregnant, and preeclamptic women. These observations suggest that a plasma factor may affect the action of prostacyclin during pregnancy. PMID- 3107391 TI - Conservative management of a severely Rh-sensitized pregnancy. PMID- 3107392 TI - The effects of laser smoke on the lungs of rats. AB - The sequelae of long-term inhalation of carbon dioxide laser smoke on 10 white rats were studied in a three-phase experiment. The fine particulate matter resulting from tissue vaporization was deposited in the animals' alveoli, which produced congestive interstitial pneumonia, bronchiolitis, and emphysema. The pathologic findings induced by laser plume are not dissimilar to those resulting from the long-term inhalation of other types of particulate matter. Use of an efficient smoke evacuator should offer substantial protection against these normal effects. PMID- 3107393 TI - Systemic mononuclear-cell vasculitis in MRL/Mp-lpr/lpr mice. A histologic and immunocytochemical analysis. AB - The cellular mechanisms governing the expression of mononuclear cell vasculitis are poorly understood. For determination of the precise sequence of events in the development of vasculitis in autoimmune MRL/lpr mice, histologic sections from 4 20-week-old mice were evaluated with a panel of cytochemical and immunohistochemical stains. The results show that vascular disease in MRL/lpr mice develops as follows: Thy 1+, Ly 1+, L3T4- T cells assemble around predominantly small-to-medium muscular arteries at approximately 8 weeks of age. At 12 weeks of age, an adventitial inflammatory focus forms, composed of large "reactive" mononuclear inflammatory cells adjacent to hypertrophied vascular smooth muscle cells (VSMCs). Blastic Thy 1+, Ly 1+, L3T4- T cells subsequently infiltrate the tunica media, and selective VSMC karyolysis results. Occasional cytotoxic/suppressor T cells, macrophages, and possibly NK cells are noted primarily distal to the infiltration site. The outer zone of the inflammatory infiltrate is composed of mature B cells and occasional B-cell precursors. These findings suggest that cellular constituents of the immune response mediate mononuclear cell vasculitis in MRL/lpr mice. PMID- 3107394 TI - Ultrastructural evidence that the granules of human natural killer cell clones store membrane in a nonbilayer phase. AB - Electron-microscopic examination of five LGL clones, JT3, JTB18, CNK6, CNK7, and CNK10, expressing natural killer activity and T11 and NKH1 phenotype, showed that three of the clones, JT3, CNK6, and CNK7, had crystalline structures in their densest granules. These structures generally consisted of hexagonally packed lattices with a 6.9-nm point-to-point spacing. JTB18 and CNK10 had no structures in their granules. The attack of one clone, JT3, on two resistant target tumor cell lines, KG1 and Laz509, was also examined under three conditions. First, JT3 cells and targets were incubated together. There was little adherence, degranulation, or killing. Second, cells were incubated with anti-T11(2) and T11(3), antibodies against the E-rosette receptor/antigen complex, which activate resting T cells and enhance cytolytic activity of NK clones and CTL. JT3 cells adhered to the targets, formed zones of apposition between NK and target cell membranes, polarized, and degranulated into the space between the two cells, killing the targets. Third, cells were incubated with both anti-T11(2/3) and anti LFA-1, an antibody that inhibits adherence. The JT3 cells did not form zones of apposition with the targets, but degranulated in discrete areas on their own surface. In all cases, discharged crystalline granules transformed to sheets of membrane and vesicles. These studies suggest that phospholipids are packed in hexagonal lattices in the granules of the resting cells and transform to bilayer structures during exocytosis. The crystalline nature of the granule may immobilize lytic molecules and protect the resting cell from lysis. Further, the vesicles may serve to transport the lytic molecules from the effector to the target cell. Anti-LFA-1 does not inhibit target recognition or exocytosis, but instead blocks membrane interactions of the effector cell with its target. PMID- 3107396 TI - On the eruption pattern of the permanent incisors and first permanent molars in Paranthropus. AB - It has been claimed recently that Australopithecus exhibited a pattern of permanent tooth eruption like that of extant great apes, whereas a significantly different pattern was shared by Paranthropus and Homo (Dean, 1985). More particularly, each of the four Paranthropus specimens examined in that study was held to show advanced development and eruption of the permanent incisors relative to the first molar. It is demonstrated here that the eruption sequence that was posited for at least one of these four Paranthropus specimens (SK 61) is clearly erroneous, while the developmental/eruption sequences manifested by the other three specimens would appear to be more ambiguous than was claimed. Another juvenile specimen of Paranthropus (KNM-ER 1820) that was not included in Dean's study also does not necessarily support the eruption pattern that was said to characterize that taxon. PMID- 3107395 TI - The H-RS-like cells in infectious mononucleosis are transformed interdigitating reticulum cells. AB - The lymphoid tissues from patients with infectious mononucleosis or, less frequently, with other reactive conditions may contain Reed-Sternberg (RS)-like cells. These tissues also contain cells resembling the lacunar cells or lymphocytic/histiocytic (L/H) variants, which are present in the lymphocyte predominant type of Hodgkin's disease. The phenotype of these RS- and L/H-like cells was determined with a large panel of antibodies and lectins. The cells expressed sialylated Leu-M1, Con A, LN-2, and, less frequently, interleukin-1, S 100, and peanut agglutinin receptor. They reacted negatively with two markers for RS cells, Ki-1 and HeFi-1. These RS-like cells were consistently negative for T- and B-cell markers, including immunoglobulins. The markers of the RS-like cells are distinctly different from those in B-immunoblasts, but closely resemble those in interdigitating reticulum cells. It is concluded that interdigitating reticulum cells, when stimulated, can be transformed into lacunar-, L/H-, or RS like cells. PMID- 3107397 TI - Evolution of the lumbosacral angle. AB - The lumbosacral angle (LSA) was studied in 131 children ranging in age from birth to 5 years. This angle increases from an average of 20 degrees at birth to an average of 70 degrees at the age of 5 years; it remains at that level thereafter. This study demonstrates that the formation of the LSA is not related to increasing age, height, or weight. Nor do obstetrical requirements seems to play any major role in the formation of the lumbosacral angle. Rather, it appears that the development of the LSA is related to the progressive acquisition of erect posture and the ontogeny of bipedal locomotion. This angle is almost nil in the nonprimate mammals (who only infrequently stand erect). It is minimal in monkeys who occasionally assume bipedal postures and increases somewhat in living apes who engage in facultative bipedal positional behavior. In the early australopithecines, the LSA is increased over that in apes, and it reaches its maximum in Homo sapiens. Deviations from normal and healthy erect posture in Homo sapiens result in corresponding changes in the lumbosacral angle. Lumbar and sacral angles (both forming the lumbosacral angle) are almost equal in all mammalian species. Since the sacral angle of Australopithecus afarensis is approximately 15 degrees, it can be implied that its lumbosacral angle was small, thus attesting to its "imperfect" erect posture and "primitive" form of bipedal locomotion. PMID- 3107398 TI - Bone breakage in the Krapina hominid collection. AB - The fragmentary condition of the Krapina Neandertal remains has been offered as one line of evidence for the hypothesis that these hominids were the victims of cannibals seeking marrow and brains. Two other hypotheses regarding the causes of the framentation have been raised: a substantial portion of the breakage in the Krapina collection is attributable to excavation damage; and the rest of the breakage is attributable to sedimentary pressure and to natural rock falls that occurred during the site's prehistory. The purpose of this paper is report on tests of these three hypotheses concerning the cause of breakage in the Krapina material. Microscopic inspection of all Krapina hominid specimens showed that 23% of the material was inadvertantly broken during excavation or during quarrying that took place at the end of the last century. The morphology of the prehistoric breakage is inconsistent with the cannibalism hypothesis and supports the hypothesis that prehistoric breakage was caused by sedimentary pressure and/or roof falls. PMID- 3107399 TI - Mortuary practices at the Krapina Neandertal site. AB - It has often been reported that the Krapina Neandertal remains bear incised linear striations which appear to be cutmarks. Here, the plausibility of the striations as cutmarks is tested by comparing them to Mousterian butchery marks on large fauna and to cutmarks on modern human skeletons known to have been defleshed with stone tools. The anatomical location, gross appearance, and frequency of occurrence of the striations on the Krapina material do not resemble Mousterian butchery marks on reindeer. The Krapina striations do closely match authenticated cutmarks on 22 modern human skeletons defleshed with stone tools after partial decomposition, preparatory to secondary burial. Data are presented supporting the hypothesis that the striations on the Krapina Neandertal remains are consistent with postmortem processing of corpses with stone tools, probably in preparation for burial of cleaned bones. PMID- 3107400 TI - Functional characterization of cell-to-cell coupling in cultured rat aortic smooth muscle. AB - Gap junction (GJ) occurrence and function was studied in cultured rat aortic smooth muscle cells, since cell-to-cell coupling is proposed to coordinate smooth muscle function but is difficult to study in the intact tissue. Cell proliferation in vitro formed a multilayered structure 10-15 cells thick. GJs connected cells to lateral and vertical neighbors, appearing in freeze fracture as P-face particles aggregated into circular plaques but also as linear arrays. The membrane potential was 58 +/- 3 mV. From quantification of the spread of electrotonic potentials according to a two-dimensional model, the intercellular resistivity was 900-1,400 omega X cm, whereas the nonjunctional membrane resistivity was 10(4) omega X cm2. Intercellular spread of 5(6) carboxyfluorescein (CF; mol wt 376) in aortic cultures suggests that metabolic coupling is an important consequence of GJs in smooth muscle. CF transfer was not blocked by A23187 (10(-5) M), although rat fibroblasts became uncoupled by 10(-6) M. Ultimately uncoupled by the more potent ionophore ionomycin (10(-5) M), aortic cells seem more able to maintain GJ permeability during challenge from increased intracellular Ca than cells of noncontractile origin. PMID- 3107401 TI - Use of adult rat cardiomyocytes to study cardiac glycogen metabolism. AB - The use of adult rat cardiomyocytes to model cardiac glycogen metabolism was investigated by monitoring the response of glycogen phosphorylase and glycogen synthase to epinephrine and insulin treatment. Cardiomyocytes derived from normal rats respond to epinephrine in the range of 1 X 10(-7) to 5.5 X 10(-6) M epinephrine with an increase in the percent of phosphorylase in the AMP independent form from 11.5 to 24.8%. In the same cells, insulin in the range of 10(-9) to 10(-7) M increased the glucose 6-phosphate independent form of glycogen synthase from 30.5 to 40.5%. Cells derived from alloxan-diabetic hearts exhibit a hypersensitive phosphorylase activation and a refractile synthase inactivation in response to epinephrine treatment. This pattern is similar to that recorded using perfused heart preparations. The data presented suggests that adult rat cardiomyocytes represent a valid model of glycogen metabolism in both the normal and alloxan-diabetic rat. PMID- 3107402 TI - Pancreatic calcification and stone formation: a thermodynamic model of calcium in pancreatic juice. AB - CaCO3 is a major constituent of pancreatic stones, salivary stones, and many pigment gallstones. Elucidation of the physicochemical state of calcium is necessary for definition of calcium solubility in these systems. Pancreatic stones are observed in both humans and cattle, and are approximately 95% CaCO3 (calcite) in both species. Despite its importance, little is known about the physicochemical state of calcium in pancreatic juice. This paper presents an a priori model, based on established physicochemical principles, for the state of calcium in the juice at all levels of secretion. Two postulates of the model are the following: the limiting free [Ca2+] in the juice is governed by the solubility product (K' sp) for CaCO3; if K' sp is exceeded, the juice is supersaturated and precipitation of CaCO3 is thermodynamically possible; total calcium, [Ca], in the juice is the sum of four distinct species: free ionized calcium, Ca2+; calcium-bicarbonate complex, CaHCO3+; calcium carbonate ion-pair, CaCO3(0); and protein-bound calcium, CaProt. Overall equations of the model and graphical corollaries are presented. The model predicts an inverse hyperbolic relationship between [Ca2+] or [Ca] and [HCO3-]. Calcium solubility is maximal at low [HCO3-]; as [HCO3-] increases, both [Ca2+] and [Ca] decline to respective limiting values of approximately 0.015 and 0.15 mM. At low [HCO3-], most of [Ca] is present as Ca2+ and CaProt, whereas at high [HCO3-], most [Ca] is CaHCO3+ and CaCO3(0). Protein, HCO3-, and CO3(2-) ions are thus important buffers for Ca2+ in the juice. The model provides a quantitative framework for further elucidation of calcium lithogenicity in the pancreas, salivary gland, and biliary tract. PMID- 3107403 TI - Free radical-mediated endothelial damage in blood vessels after electrical stimulation. AB - The endothelium plays an important role in mediating vasodilator effects of several agents (acetylcholine, thrombin, A23187, etc.). The goal of this study was to determine the ability of oxygen free radicals generated by electrical field stimulation to alter endothelial function in isolated tissue systems. Tail artery strips and the mesenteric microvasculature isolated from Sprague-Dawley rats were used. Following smooth muscle contraction induced by norepinephrine, these preparations relaxed in response to acetylcholine chloride or ionophore A23187. All vessels were then subjected to electrical stimulation (9 V, 1-2 ms, 4 Hz) of the physiological buffer in which they were bathed or perfused. In some of these preparations, an antioxidant, (10(-4) M sodium ascorbate, 3.6 X 10(-5) M glutathione, 1.3 X 10(-2) M dimethyl sulfoxide) was included in the buffer. Relaxation responses persisted in vessels where an antioxidant had been included in the electrically stimulated buffer. Tissues stimulated without this protection did not relax on subsequent exposures to endothelium-dependent vasodilators. Scanning-electron microscopy of the tissues revealed significant endothelial damage (cell membrane pitting) in tissues exposed to electrical stimulation without antioxidant protection. These results suggest that electrical stimulation causes endothelial damage in isolated vascular preparations. This seemingly adverse effect proves to be a useful tool for removing the endothelium in studies of isolated vascular tissues. PMID- 3107404 TI - Thermogenin amount and activity in hamster brown fat mitochondria: effect of cold acclimation. AB - To investigate the acclimation process in a hibernator, four different parameters of thermogenin amount and activity were investigated in brown adipose tissue mitochondria from cold-exposed and cold-acclimated Syrian hamsters. Hamsters, which are hibernators, have been considered to be "primed" for thermogenesis and thus not to show cold-acclimation effects, but here a significant increase in [3H]GDP-binding capacity was observed (from 0.5 nmol in control to 0.9 nmol GDP/mg in cold-acclimated hamsters), and this increase was paralleled by an increase in thermogenin antigen amount, as measured in an enzyme-linked immunosorbent assay. The transient nature of the effect of cold exposure on [3H]GDP binding, characteristically observed with rat mitochondria, was not observed with hamster mitochondria, and the increase in [3H]GDP binding occurred without a change in the dissociation constant (0.7 microM). The increase in thermogenin amount was paralleled by an increase both in GDP-sensitive Cl- permeability of the mitochondria and in GDP-sensitive respiration. It was established that it is the maximal activity of thermogenin that is rate limiting for thermogenesis in isolated mitochondria, provided that an optimal substrate is used (such as palmitoyl carnitine). Cold acclimation also increased the total amount of mitochondria in the tissue, leading totally to a sixfold increase in thermogenin content of the hamster. It is concluded that (contrary to the general view) hamsters show the expected physiological, pharmacological, and biochemical signs of cold acclimation (i.e., an increased capacity for nonshivering thermogenesis). PMID- 3107405 TI - Quaternary ammonium sulfanilamide: a membrane-impermeant carbonic anhydrase inhibitor. AB - A novel carbonic anhydrase (CA) inhibitor, quaternary ammonium sulfanilamide (QAS), was tested for potency as a CA inhibitor and for its ability to be excluded from permeating biological membranes. Inhibitor titration plots of QAS vs. pure bovine CA II and CA from the gills of the blue crab, Callinectes sapidus, yielded Ki values of approximately 15 microM; thus QAS is a relatively weak but effective CA inhibitor. Permeability of the QAS was directly tested by two independent methods. The inhibitor was excluded from human erythrocytes incubated in 5 mM QAS for 24 h as determined using an 18O-labeled mass spectrometer CA assay for intact cells. Also QAS injected into the hemolymph of C. sapidus (1 or 10 mM) did not cross the basal membrane of the gill. The compound was cleared from the hemolymph by 96 h after injection, and at no time during that period could the QAS be detected in homogenates of gill tissue. Total branchial CA activity was only slightly reduced following the QAS injection. These data indicate that QAS is a CA inhibitor to which biological membranes are impermeable and that can be used in vivo or in vitro in the study of membrane associated CA. PMID- 3107406 TI - Membrane-associated carbonic anhydrase in gills of the blue crab, Callinectes sapidus. AB - The presence of the enzyme carbonic anhydrase (CA) on the basal membrane of the branchial endothelial cells in the blue crab and its physiological significance were studied in vivo using a membrane-impermeant CA inhibitor, quaternary ammonium sulfanilamide (QAS). Injection of QAS into the hemolymph of Callinectes sapidus resulted in the rapid development of a respiratory acidosis; PCO2 rose almost 2 Torr, pH was lowered by approximately 0.25 units, and total CO2 rose by 2 mM. These results support the hypothesis that membrane-associated CA exposed to hemolymph is present in the crustacean gill and that it is physiologically significant in mobilizing hemolymph HCO-3 to CO2 to facilitate CO2 excretion across the gill. The recovery from this acidosis coincides with the clearance of the inhibitor from the hemolymph. Hemolymph osmotic and ionic parameters were unaffected by QAS, reconfirming the role of branchial cytoplasmic CA in ion regulation and also providing a convenient bioassay for determining CA inhibitor permeability in the intact organism. PMID- 3107407 TI - An analysis of DRG-based reimbursement for psychiatric admissions to general hospitals. AB - The authors analyzed the potential financial impact of paying general hospitals on the basis of diagnosis-related groups (DRGs) for Medicare alcohol-drug abuse and psychiatric admissions. Average costs per admission were substantially higher for general hospitals with special psychiatric units that are currently exempt from the prospective payment system (PPS) than for hospitals without exempt units. Simulations of DRG-related payments indicated that these payments would be greater for admissions to hospitals with exempt psychiatric units than for admissions to hospitals without exempt units. However, the differences in costs between these two types of facilities were greater than the differences in payments that would occur under a PPS. PMID- 3107409 TI - Exotic stock of Trypanosoma cruzi (Schizotrypanum) capable of development in and transmission by Triatoma protracta protracta from California: public health implications. AB - A stock of Trypanosoma cruzi was recovered from a Triatoma dimidiata from Tegucigalpa, Honduras. This stock was shown to be capable of development and transmission by native California Triatoma protracta protracta. Isozyme analysis indicated that this T. cruzi is closely related to the Tehuantepec strain and to a lesser extent the Miles' zymodeme 1 strain. The potential public health significance of development and transmission of exotic stocks of T. cruzi by native reduviids is discussed. PMID- 3107408 TI - Bringing psychiatric patients into the Medicare prospective payment system: alternatives to DRGs. AB - The basis of Medicare's prospective payment for alcohol, drug abuse, and mental illness hospital admissions has been the patient classification system known as diagnosis-related groups (DRGs). This paper describes two alternative patient classification systems, disease staging and clinically related groups, and reports how well each system predicts resource use compared to the DRG system. Medicare data from four states were used to test the comparative strength of these patient classification systems. Although disease staging and clinically related groups performed better than DRGs, they were still poor predictors of resource use. PMID- 3107410 TI - Insect-borne and culture-derived metacyclic Trypanosoma cruzi: differences in infectivity and virulence. AB - We report in this paper significant differences in the virulence of insect derived and cultured metacyclic forms of Trypanosoma cruzi which are morphologically indistinguishable. Mice infected intraperitoneally with 10(3) metacyclic T. cruzi isolated from Rhodnius prolixus showed average parasitemia levels greater than 2 X 10(5) organisms/ml around day 10 post-infection (when first measured) and peak levels recorded on day 16 post-infection exceeded 4 X 10(7) organisms/ml. None of these animals survived after 30 days post-infection. In contrast, in mice infected with 10(3) or 10(4) metacyclic forms from axenic cultures the highest average parasitemia was approximately 10(4) organisms/ml and occurred around day 19 post-infection. In these animals, parasitemias declined with time to become undetectable and no mortality was recorded over the 100-day observation period. There was also a marked difference in the 50% lethal dose of insect- and culture-derived metacyclics. The value for the former was 670 parasites whereas none of the mice infected intraperitoneally with up to 10(6) cultured metacyclics died. These results point to a marked difference in the biological properties of insect-borne and cultured T. cruzi metacyclics under our experimental conditions and caution against extending results obtained with the latter to vector-transmissible metacyclics, at least in infectivity and virulence studies. PMID- 3107411 TI - Factors influencing Rickettsia tsutsugamushi infection of cultured cells. AB - Several factors which influence Rickettsia tsutsugamushi infectivity of, and replication in, cultured cells have been investigated in order to establish standard laboratory conditions for reliable quantitation and maximization of rickettsial yield and to begin to explore the nature of the relationship between the rickettsia and its host cell. The extent of scrub typhus rickettsial association with host cells was dependent on the rickettsial and target cell concentrations and on the medium in which the infection took place. Brain heart infusion broth, a standard rickettsial diluent for infectivity, was markedly inhibitory. Both rickettsial and host cell replication were dependent on a component(s) supplied by serum to the tissue culture medium; rickettsial multiplication was less affected by small temperature variation (optimum 34 to 37 degrees C) than was host cell growth (optimum 37 degrees C). The antibiotic daunomycin was very useful in selectively inhibiting host cell replication and permitting attainment of somewhat greater rickettsial yields than in uninhibited cells. These findings have underscored the close relationship between parasite and infected cell and have led to more predictable, higher yields of rickettsiae in vitro. PMID- 3107413 TI - Emergency management of choledochal cysts in adult patients. AB - Congenital cystic dilation of the biliary tree is rarely considered as cause of cholangitis in the adult patient. Emergency operation in seven adults with unsuspected choledochal cysts resulted in reoperation in all seven. Each patient presented with right upper quadrant pain, a mass, and cholangitis or jaundice. Abdominal ultrasonography incorrectly identified the cyst as a dilated gallbladder in three of the patients. All initial emergency drainage procedures required subsequent modification to cyst excision and Roux-Y reconstruction. From review of the experience presented and the literature to date, we recommend that otherwise stable patients be managed nonsurgically and undergo endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography to plan primary single-stage excisional operation. Patients requiring emergency decompression should have cholecystostomy or choledochostomy for good control without compromising subsequent operation. At the time of excision, a technical consideration not previously reported is the presence of small daughter cysts in Calot's triangle which must be distinguished from the hepatic bile ducts. The surgical literature has frequently addressed the problems of elective surgery for choledochal cysts; however, emergency complications requiring urgent operative intervention are seldom addressed. We believe emergency intervention should correct the urgent complication without compromising the definitive surgical treatment. PMID- 3107412 TI - Improved plaque assay for Rickettsia tsutsugamushi. AB - The assay of Rickettsia tsutsugamushi infectivity by plaquing has been improved substantially by a number of changes which were based on our understanding of factors which enhance scrub typhus rickettsial infection of, and replication in, cultured cells. Greater numbers of plaques and/or larger plaques resulted from: use of tissue culture medium instead of brain heart infusion broth as the rickettsial diluent; plaquing in a contact-inhibited mouse embryo cell line rather than in growth-inhibited or uninhibited Vero cells; infection and incubation of monolayers at 35 degrees C instead of at lower temperatures; frequent feeding of infected cultures with medium containing ample amounts of serum; and inclusion of chicken serum in the overlay medium. Plaquing in 24-well tissue culture plates instead of in petri dishes or flasks greatly simplified the handling of large numbers of samples and was beneficial economically as well. Easily recognized rickettsial plaques were counted microscopically under x40 magnification, and maximum counts were obtained 12-14 days after infection, depending on the rickettsial strain. Slightly longer incubation yielded macroscopically visible counts. In addition to enhancing plaque number and size, the changes in standard R. tsutsugamushi plaquing methods resulted in an easier, faster, and more reliable assay, with improved reproducibility of plaque formation, maintenance of infected cell monolayers, and avoidance of microbial contamination. PMID- 3107414 TI - Nonoperative observation therapy for splenic injuries: a safe therapeutic option? AB - Combining these reported and estimated incidences of mortality from overwhelming postsplenectomy infection, splenic salvage with nonoperative observation therapy and operative therapy, and the incidence of posttransfusion hepatitis and related mortality provides a conditional probability estimation of the risks of death with nonoperative observation therapy and operative therapy (Figure 4). The combined mortality rates for nonoperative observation and operative therapies are based on the following measured and estimated statistics: The post-transfusion hepatitis death rate per unit of blood transfused is 0.14 percent. Forty percent of children and 20 percent of adults who have successful nonoperative observation therapy receive an average of 2 units of blood. One hundred percent of children and adults in whom nonoperative observation therapy is unsuccessful receive an average of 4 units of blood. Twenty percent of children and adults who undergo operation initially receive an average of 2 units of blood. Ten percent of observed children require laparotomy and 75 percent of these patients then undergo splenectomy. Forty percent of adults who have nonoperative observation initially later require laparotomy, 93 percent of whom also require splenectomy. Ten percent of children and adults treated with initial operation later require splenectomy. Death from overwhelming postsplenectomy infection occurs in 0.026 percent of adults who undergo splenectomy and 0.052 percent of children who undergo splenectomy. Given these assumptions, the conditional probability of death in a child who initially undergoes nonoperative observation therapy is 0.17 percent compared with 0.06 percent for initial operative therapy. In adults, 0.26 percent of the observed patients die compared with 0.06 percent for those operated on initially. As stated, many of the percentages or probabilities listed are estimations based on the best available clinical data. The inability to establish a mortality rate from overwhelming postsplenectomy infection remotely resembling that reported for otherwise healthy patients required an unsubstantiated estimate. However, even when mortality rates from overwhelming postsplenectomy infection of 0.43 percent and 0.6 percent were substituted, early laparotomy still produced lower mortality rates. This continues to be true if one assumes that early laparotomy will result in 50 percent or even 100 percent of patients undergoing splenectomy, although in these cases the statistical differences would be less. We acknowledge that these statistics may exceed or underestimate the true risk of either treatment plan.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3107415 TI - Causes of Rh sensitization in Alabama. PMID- 3107416 TI - Nutritional support of the critically infected patient. PMID- 3107417 TI - Anaesthesia for combined heart and lung transplantation. AB - In December 1983, Harefield Hospital started a programme for combined heart and lung transplantation. Fifty-two transplants have been successfully performed, with 36 survivors (April 1986). Patient selection and anaesthetic management of both donor and recipient are discussed. Two case histories are presented which illustrate the principles of anaesthetic management and postoperative care. PMID- 3107418 TI - [ARDS following amniotic fluid embolism. Case report of successful long-term intensive therapy]. AB - A case of severe ARDS following amniotic fluid embolism is described. During the 15 month period of I.C.U. treatment a number of respiratory complications had to be overcome. Chronic hypercapnia led to changes of bone and soft tissue composition. The patient was discharged home with a marked restriction of pulmonary function. Respiratory infections continue to occur. PMID- 3107419 TI - [Effect of Disoprivan (propofol) on the circulation and oxygen consumption of the brain and CO2 reactivity of brain vessels in the human]. AB - The effects of Disoprivan on cerebral blood flow (CBF), cerebral oxygen consumption, and CO2-reactivity of the cerebral vessels were studied in 11 male patients between 49 and 63 years of age who were about to undergo coronary artery bypass surgery. Mean perfusion pressure was decreased by 25% under anaesthesia by 0.2 mg/kg per minute Disoprivan, but remained within the ranges of autoregulation. CBF decreased by 51% and cerebral vascular resistance (CVR) increased by 55% following a 36% decrease in cerebral oxygen consumption which was associated with a decrease in neuronal activity in the EEG. Hyperventilation led to a 25% further decrease in CBF due to a 43% increase in CVR while cerebral oxygen consumption remained unchanged. Hypoventilation was followed by a 67% increase in CBF and a 44% decrease in CVR cerebral oxygen consumption was decreased by 38%. This study shows that the reactivity of the cerebral vessels to changes in paCO2 is well maintained under Disoprivan. PMID- 3107420 TI - [ABS 800: expanding the possibilities of respiratory therapy]. AB - A new module of the Drager modular device system provides a means for demand CPAP (to increase FRC) and assisted spontaneous breathing. Both features together may largely increase the potency of ventilatory therapy for spontaneously breathing patients. The machine may reduce the need for full ventilatory support in acute respiratory failure, but also provides a valid and rational tool for respiratory therapy. PMID- 3107421 TI - Radioiodination and 125I-labeled peptide mapping of proteins on nitrocellulose membranes. AB - A rapid procedure for generating dozens of 125I-labeled peptide maps from a protein band excised from a single lane of a sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) gel has been developed. Proteins, which can be rapidly purified by 2 X SDS-PAGE separation, are electroblotted onto nitrocellulose paper (NCP) and located by aqueous naphthol blue-black staining. All subsequent steps of radioiodination, and enzyme or chemical cleavage, are carried out on the NCP making it possible to test a variety of cleavage reagents on the same protein sample. The resultant peptidic residues, which can be separated by thin-layer electrophoresis-thin-layer chromatography (2D TLE-TLC), SDS-PAGE, or HPLC, can be used in comparative studies or they can be recovered for further structural and immunological analyses. PMID- 3107422 TI - Thermal gels: a procedure for determination of heat-inactivation temperature of enzymes. AB - A facile procedure for the study of inactivation temperatures of enzymes that could be stained for activity after electrophoresis is described. This is particularly suitable for enzymes that have multiple electrophoretic forms. The results of studies on Drosophila dehydrogenases and acetylcholinesterase are presented. The procedure may be useful in the study of genetic variants. PMID- 3107423 TI - Synthesis of NG-monomethylagmatine, a decarboxylation product of NG-monomethyl-L arginine. AB - NG-Monomethylagmatine, a decarboxylation product of NG-monomethyl-L-arginine, has been synthesized by reacting putrescine with N,S-dimethylthiopseudouronium iodide. The structural identity of the product was confirmed by proton NMR and mass spectroscopy, and its properties were determined on thin-layer and electrophoretic chromatography. PMID- 3107424 TI - Effects of different batches of 125iodine on properties of 125I-hFSH and characteristics of radioligand-receptor assays. AB - Radioiodination of highly purified human follicle-stimulating hormone (hFSH) (4000 IU/mg) was performed every other week for 23 weeks using 2 mCI carrier free Na125I (Amersham Corp., 15 mCi/micrograms I2) in the presence of lactoperoxidase. Incorporation of 125I into hFSH was determined by the method of R. C. Greenwood, W. M. Hunter, and J. S. Grover (1963) Biochem. J. 89, 114). Hormone binding was studied in vitro under steady-state conditions (16 h, 20 degrees C) using different calf testis membrane preparations having similar receptor characteristics. Each 125I-hFSH preparation was characterized for maximum bindability, specific activity of bindable radioligand as determined by self displacement analysis, and by determination of Ka and Rt. Incorporation of 125I into FSH was relatively constant over the large number of experiments (62.4 +/- 6.4 microCi/micrograms; n = 23). By comparison, however, specific radioactivity of the receptor bindable fraction of 125I-hFSH was related to the lot of 125I utilized, and was significantly (P less than or equal to 0.01) lower and more variable (28.7 +/- 10.5 microCi/micrograms). Maximum bindability of 125I-hFSH was not correlated to specific activity (r = 0.06) but was negatively correlated to hFSH 125I incorporation (r = -0.47; P less than or equal to 0.05). These observations demonstrate the need to assess the quality of each batch of radioligand before undertaking radioligand-receptor assays and suggest that differences in Na125I lots affect specific radioactivity of the radioligand and its receptor binding characteristics. PMID- 3107425 TI - A selective extraction of growth hormone from bovine pituitary gland and its further purification and crystallization. AB - A highly efficient method for the isolation of bovine growth hormone (GH) is described. The method is based on selective extraction of GH from 15,000 g subcellular sediment of anterior pituitary gland with 130-150 mM NH4HCO3, 1 mM EGTA, pH 7.2-7.4, at 2-6 degrees C for 60 min, purification of the extracted GH by ammonium sulfate fractionation, one-step ion-exchange column chromatography on DEAE-cellulose (or CM-cellulose), and gel filtration on Sephadex G-75. This 2-3 day procedure provides a highly pure hormone in high yield (up to 70-80 mg per 35 40 g of the whole pituitary gland), which can be crystallized by the batch method at a low ionic strength and isoelectric pH. PMID- 3107427 TI - The use of N-[beta-(4-diazophenyl)ethyl]maleimide as a heterobifunctional agent in developing enzyme immunoassay for neurotensin. AB - A heterobifunctional crosslinking agent N-[beta-(4-diazophenyl)ethyl]maleimide (DPEM) was newly synthesized and characterized to possess the maleimide group with a stability greater than that previously reported for N-(4 diazophenyl)maleimide. Using the peptide hormone neurotensin (NT) as a model hapten, DPEM was used in the conjugation reaction with bovine serum albumin (BSA) and with beta-D-galactosidase (beta-Gal) in developing an enzyme immunoassay (EIA) for NT. The NT-DPEM-BSA conjugate elicited anti-NT antibodies in rabbits and the NT-beta-Gal conjugate behaved as an enzyme marker of NT in the EIA. The EIA developed double antibody was reproducible and sensitive in detecting NT at concentrations as low as 30 fmol per tube. The specificity of anti-NT serum seems to be primarily toward the carboxy-terminal region of NT, showing cross-reactions with such NT fragments as NT2-13, NT8-13, and NT1-8 for 120, 22, and less than 0.1%, respectively. The utility of this assay was also demonstrated by measuring the NT immunoreactivity in several rat organs. DPEM could be useful for developing EIAs for other peptide hormones (even those which contain neither a free amino group nor a free carboxyl group), using the imidazole, phenolic, or indole group(s) of amino acids as a binding site for carrier proteins. PMID- 3107426 TI - Extraction of starch by dimethyl sulfoxide and quantitation by enzymatic assay. AB - A method for the rapid, sensitive, and specific determination of starch in plant tissues is described. Starch from a variety of plant tissues is solubilized by stirring for 24 h or by sonication for 40 min in dimethyl sulfoxide. Dilution of this extract to less than 20% dimethyl sulfoxide permits a nearly complete hydrolysis of the starch in less than 3 h with glucoamylase from Rhizopus niveus. Quantitation of liberated glucose by a coupled hexokinase and glucose-6-phosphate dehydrogenase method provides an additional degree of specificity. PMID- 3107428 TI - Antibody for detection and quantitation of membrane-associated folate-binding protein from Lactobacillus casei. AB - Lactobacillus casei cells contain a 25 kDa, membrane-associated, folate-binding protein (fbp), which is a component of the folate transport system. Polyclonal antibody to fbp (anti-fbp) has been prepared, and conditions have been established for detection and quantitation of the protein. Anti-fbp did not block [3H]folate transport or binding in L. casei cells. As judged by Western blots, the antibody reacted only with fbp on sodium dodecyl sulfate electrophoretograms of Triton X-100 extracts of L. casei membranes. Anti-fbp showed no cross reactivity with L. casei dihydrofolate reductase, L. casei 5,10 methenyltetrahydrofolate synthetase, L1210 dihydrofolate reductase, rat liver dihydrofolate reductase, or L1210 folate-binding protein. Enzyme-linked immunosorbent assay measurements indicated the presence of an fbp in membranes of Lactobacillus salivarius and two transport-defective sublines of L. casei. Anti fbp was used to demonstrate selective extraction, with n-butanol, of fbp from a mixture of Triton-solubilized L. casei membrane proteins; repression of fbp in membranes of L. casei cells grown on high levels of folate; and localization of fbp by electron microscopy, using anti-fbp in conjunction with goat anti-rabbit IgG gold conjugate, in L. casei membranes. PMID- 3107430 TI - Butorphanol improves CO2 response and ventilation after fentanyl anesthesia. AB - We have determined that the mixed agonist-antagonist narcotic, butorphanol, improves CO2 response and ventilation after fentanyl anesthesia. A tentative dosage range has been established. Twenty-two patients were anesthetized with isoflurane, nitrous oxide, and fentanyl, which was continuously infused throughout the study. Postoperatively three 1-mg doses of butorphanol were administered IV. Blood pressure, heart rate, plasma epinephrine and norepinephrine concentrations, and pain intensity were essentially unchanged after butorphanol. Most of the improvement in breathing occurred after the first 1-mg dose. Mean respiratory rate increased from 7.8 +/- 5.0 to 11.0 +/- 4.8 min-1 (P less than or equal to 0.005), tidal volume increased from 469 +/- 302 to 844 +/- 390 ml (P less than or equal to 0.005), minute ventilation increased from 4.32 +/- 2.97 to 8.51 +/- 3.14 L/min (P less than or equal to 0.005), and the slope of the ventilatory response to CO2 increased from 0.36 +/- 0.37 to 0.90 +/- 0.80 L X min-1 X mm Hg-1 (P less than or equal to 0.05). Resting PaCO2 decreased from a baseline of 57.8 +/- 11.1 to 51.7 +/- 5.12 mm Hg (P less than or equal to 0.05) after the third dose. PMID- 3107429 TI - Vertical ascending connections in the isocortex. AB - Different fluorescent tracers were applied to the surface of the cortex of rats, marmosets and one hedgehog. Irrespective of the kind of tracer and the depth of penetration, some perikarya of layer VI were labelled in each specimen and in all cortical regions. In the rat almost all labelled neurons were packed in sublayer VIb, in the marmoset such cells were dispersed throughout layer VI, whereas in the hedgehog the degree of their segregation to sublayer VIb was intermediate. Additional experiments in the rat indicated that most of the medium-sized neurons in the VIb layer project to layer I, that most of the perikarya projecting to the thalamus are localized in sublayer VIa, that different neurons project to the thalamus and to the surface of the cortex, and that only very few perikarya in deep parts of layers III and V and of sublayer VIa send axons or axon collaterals to layers I and II. PMID- 3107431 TI - Tidal volumes required to maintain isocapnia at frequencies from 3 to 30 Hz in the dog. AB - We ventilated seven mongrel dogs with high frequency oscillatory ventilation (HFO) at frequencies from 3 to 30 Hz. At each frequency, the tidal volume required to achieve isocapnia (VTiso) was measured by plethysmography. In an individual dog, VTiso could be related to frequency by an equation of the form VTiso = KfA. A was similar for the seven dogs, A = -0.54 +/- 0.03. K varied from 179 to 325 cc- Hz-A, reflecting differences between the dogs in dead space, CO2 production and gradient for gas transport. This relation is consistent with that predicted from the data of previous investigators who used different ventilators, circuits and methodology. From 3 to 30 Hz, VTiso decreased from 1.2 to 0.4 times anatomic plus equipment dead space, but minute volumes required to maintain isocapnia increased from 6 to 18 times those required during conventional ventilation. We conclude that low tidal volume ventilation is also high minute volume ventilation. PMID- 3107433 TI - Is fentanyl an anesthetic in the dog? AB - The authors used the absence of vocalization and movement during application of a hemostat clamped to the first ratchet at the base of the tail as an indication of anesthesia for evaluation of the anesthetic properties of fentanyl in the dog. Eighty-six unpremedicated, unrestrained, untrained mongrel dogs were given one of eight doses of fentanyl citrate (125, 250, 500, 750, 1000, 1500, 2000, and 3000 micrograms/kg) as a single intravenous bolus injection. Dogs breathed spontaneously without oxygen supplementation. Anesthesia was assessed every 5 min until absence of anesthesia was recorded for two consecutive evaluations. Venous plasma samples were obtained in two or three dogs receiving each of the doses of fentanyl 5 min after fentanyl injection and again when application of the tail clamp elicited either vocalization or movement (positive response). Fentanyl resulted in recumbency in all animals except two receiving 125 micrograms/kg. Although all doses of fentanyl produced anesthesia in at least one animal 5 min after injection, the duration of anesthesia was short, responses unpredictable, and anesthesia achieved in all animals only with a dose of 3000 micrograms/kg. Increasing doses of fentanyl resulted in higher plasma fentanyl concentrations 5 min after injection and at the time of the first positive response to tail clamp but there was great variability. All doses of fentanyl caused statistically significant decreases in heart and respiratory rates but none produced apnea or a PaCO2 higher than 67 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107434 TI - Induced hypotension: action of sodium nitroprusside and nitroglycerin on the microcirculation. A micropuncture investigation. AB - Sodium nitroprusside (SNP)-induced hypotension is associated with tissue hypoxia in liver and skeletal muscle, suggesting a redistribution of nutritional capillary flow. To test this hypothesis, the effects of SNP and nitroglycerin (NTG) on striated muscle vessels were studied in 42 hamsters using intravital microscopy, quantitative video image analysis, a platinum multiwire electrode for local Po2 measurements, and a micropuncture system for the determination of microcirculatory pressure. A transparent chamber was implanted in a dorsal skin fold. When the mean arterial pressure was reduced to 70 or 40 mmHg by SNP, the precapillaries dilated and precapillary resistance decreased, but significant changes in venular diameter were not observed. However, SNP-induced hypotension was associated with a consistent increase in intravascular pressure within the venules. As a result, the arteriolar-venular pressure gradient was reduced by more than 50%. Furthermore, the functional capillary density was less, and tissue hypoxia was present during SNP hypotension. In contrast, NTG dilated both arterioles and venules in the microvascular network. Despite a lower blood cell velocity in all segments, the functional capillary density and local Po2 remained unchanged during NTG, principally because there was only a 10% reduction of the arteriolar-venular pressure gradient. These findings suggest that, in terms of tissue oxygenation, NTG may be preferable to SNP for deliberate hypotension. PMID- 3107432 TI - Removal of tracheal secretions in anesthetized dogs: balloon catheters versus suction. AB - Artificial secretions were removed by suction (using 12- or 18-French suction catheters) or by means of a balloon-tipped catheter (6-French Fogarty arterial embolectomy catheter) in 20 experiments performed on five dogs anesthetized with halothane. Each dog had 5 ml of mucin injected 10 cm down the endotracheal tube prior to a 30-sec period of intermittent positive pressure ventilation. After this procedure, the ventilator was disconnected and the secretions were removed by suction with the 12- or 18-French catheters or by the Fogarty catheter. Each dog had balloon removal performed twice and suction performed once with the 12 French and once with the 18-French catheter. The endotracheal tube was cleaned and a 15-min stabilization period was allowed between each experiment. Arterial blood pressure (MAP) and pulmonary artery pressure (PAP) did not change after either technique. There were no ECG changes, arrhythmias, or alterations in PaCO2. The PaO2 was significantly lower in the two suction catheter groups [520 +/- 33 mm Hg (12 French) and 451 +/- 31 mm Hg (18 French)] than in the balloon removal group (564 +/- 10 mm Hg) (P less than 0.05). The balloon technique removed more secretions (4.52 +/- 0.06 ml) than did suction (12 French, 1.32 +/- 0.17 ml; 18 French, 2.11 +/- 0.44 ml). Balloon removal of tracheal secretions has two advantages over conventional suction techniques: it removes more secretions, and it has less detrimental effect on arterial oxygenation. PMID- 3107436 TI - Unusual end-tidal CO2 waveform. PMID- 3107437 TI - Low-dose intranasal nitroglycerine attenuates pressor response. PMID- 3107435 TI - Alteration of blood flow distribution and vascular capacitance during induced hypotension in deafferented dogs. AB - The effects of three hypotensive agents, sodium nitroprusside (SNP), nitroglycerin (NTG), and adenosine triphosphate (ATP), on blood flow distribution and vascular capacitance were examined in dogs anesthetized with sodium pentobarbital. To eliminate the modification by the baroreflex, carotid sinus was denervated and aortic and cardiopulmonary vagal fibers were sectioned. Total systemic circulation was divided into two parallel compartments, splanchnic (SP) and extra-splanchnic (ESP) vascular beds. Alteration of vascular capacitance was assessed by a change in systemic blood volume with constant cardiac output and constant venous pressure using a total heart-lung bypass. SNP- and ATP-induced hypotension caused blood flow redistribution from the SP to ESP beds, and this redistribution is greater (P less than 0.01) with ATP than that with SNP. In contrast, NTG-induced hypotension did not significantly cause redistribution. Systemic blood volume was increased during NTG- (10.4 +/- 2.2 ml/kg), and SNP induced (4.8 +/- 1.1 ml/kg) hypotension. The increase by NTG was significantly greater (P less than 0.05) than that by SNP. In contrast, ATP-induced hypotension did not significantly change systemic blood volume. Since redistribution can result in a passive change in vascular capacitance, the differences in capacitance among SNP, NTG, and ATP can be explained in part by differences in redistribution of blood flow. Redistribution of blood flow from SP to ESP beds can increase venous return due to increasing the slope of the venous return curve. The results suggest that redistribution should be taken into consideration in evaluating the hemodynamic changes during induced hypotension. PMID- 3107438 TI - [Hemodynamic effects of nitroglycerin]. PMID- 3107439 TI - [Prevention of postresuscitation heart damage with gutimine]. PMID- 3107440 TI - [Status of various neurohumoral systems during treatment of the postoperative pain syndrome by the electroacupuncture method]. PMID- 3107441 TI - Clinical experience with a transdermal nitroglycerin system. AB - Forty-seven patients with chronic stable angina pectoris entered a thirteen-week open-label study with a transdermal therapeutic system of nitroglycerin in order to evaluate its clinical efficacy, safety, and patient acceptance. In 19 patients, a beta-blocker and in 17 patients a calcium-channel blocker were continued throughout the study period without alteration of their doses. The study consisted of a two-week run-in period and an eleven-week active drug period. Acute titration was done with nitroglycerin patches on the basis of weekly patient diaries on frequency of angina and sublingual nitroglycerin consumption. Overall, reductions in frequency of angina and in nitroglycerin consumption were statistically significant (p less than 0.05). Adverse reactions were common but tolerable. The reported side effects were headache in 32, skin rash in 18, dizziness in 10, palpitation and itching in 9 each, nausea in 7, flushing in 3, and vomiting in 1 patient. In conclusion, the present study demonstrates that individual dose titration with nitroglycerin patches for obtaining significant antianginal effect is essential. The present therapeutic system is convenient to use and well tolerated and had acceptable side effects in our study population. PMID- 3107442 TI - [Assessment of the efficacy and tolerance of a benzodiazepine antagonist (Ro 15 1788)]. AB - The aim of this study was to evaluate the efficacy and the tolerance of Ro 15 1788, a specific benzodiazepine antagonist, in reversing the effects of midazolam. Six healthy male volunteers (mean age 32 +/- 3 years; mean weight 75.5 +/- 5 kg) took part in this study. Two of the three following drugs: midazolam (0.15 mg X kg-1), Ro 15-1788 (0.1 mg X kg-1) or placebo, diluted in 10 ml isotonic saline, were injected intravenously in 15 s at 5 min intervals in a double-blind manner in each subject during six randomized sessions: midazolam placebo; Ro-placebo; placebo-midazolam; placebo-Ro; midazolam-Ro; Ro-midazolam. At least four days were allowed between each session for each subject. The evaluation of the effects on the central nervous system was as follows. At the time of injection of the first drug and, if possible, at the time of injection of the second drug, the subject was asked to count aloud to 150. The following variables were timed: start of dysarthria, cessation of counting, abolition and duration of absence of the ciliary reflex and duration of induced sleep. Retrograde and anterograde amnesia were evaluated by the recall of a playing card and a number. Haemodynamic effects (variations of systolic and diastolic pressures and pulses rate) as well as respiratory ones (apnoea) were also studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107443 TI - Reversal of sleep-induced hypoventilation and chronic respiratory failure by nocturnal negative pressure ventilation in patients with restrictive ventilatory impairment. AB - The efficacy of negative pressure ventilation (NPV) in alleviating sleep-induced reductions in alveolar ventilation and in producing long-term clinical benefits was studied in 5 patients (54 +/- 8 yr of age; mean +/- SD) with chronic respiratory failure secondary to restrictive ventilatory impairment (VC, 40 +/- 14% predicted; TLC, 72 +/- 18% predicted; FEV1/FVC, 89 +/- 15%). In control sleep studies, arterial O2 saturation decreased from 81 +/- 6% during wakefulness to 79 +/- 1% during non-REM sleep and to 67 +/- 3% during REM sleep, and transcutaneous PCO2 increased from 80 +/- 16 mm Hg during wakefulness and non-REM sleep to 87 +/ 16 mm Hg during REM sleep. Nocturnal NPV in a cuirass ventilator improved baseline ventilation during wakefulness and prevented deterioration of alveolar ventilation during sleep. Upper airway obstruction during sleep induced by NPV was successfully managed with either a tricyclic medication or nasal CPAP. After 8 wk of nocturnal NPV, all patients felt considerably better. Daytime resting arterial PCO2 decreased from 56 +/- 2 to 46 +/- 3 mm Hg (p less than 0.05) and PO2 increased from 51 +/- 9 to 70 +/- 10 mm Hg (NS). Four patients have continued NPV at home on a regular basis and have returned to full-time employment. We conclude that nocturnal NPV is an effective method of preventing sleep-induced reductions in alveolar ventilation and a practical method of long-term management of patients with nonobstructive chronic respiratory failure. PMID- 3107444 TI - Effects of intermittent negative pressure ventilation on respiratory muscle function in patients with severe chronic obstructive pulmonary disease. AB - The reduced respiratory muscle strength and increased work of breathing in patients with severe chronic obstructive pulmonary disease (COPD) may predispose these patients to the development of respiratory muscle fatigue and consequent respiratory failure. To test the hypothesis that these patients may be experiencing chronic respiratory muscle fatigue, we studied the effects of resting the respiratory muscles in a group of patients with severe COPD. Fifteen stable patients with severe COPD were randomized into study and control groups. In 8 study group patients (Group B), breathing was assisted with a negative pressure ventilator 3 to 6 h daily for 3 consecutive days. The remaining 7 patients served as controls (Group A) and did not receive any intervention. Baseline lung function was evaluated by spirometry and arterial blood gas determinations. Respiratory muscle strength and endurance were evaluated by maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and the maximal duration that isocapnic hyperventilation equal to 50 and 70% of the 12-s maximal voluntary ventilation could be sustained (DSV). Baseline DSV was determined as the best effort of several practice trials. All measurements were repeated on the final day of assisted ventilation approximately 2 to 3 h after its discontinuation. After assisted ventilation, the DSV at 50 and 70% of the maximal voluntary ventilation improved significantly (p less than 0.05). Maximal inspiratory pressure and MEP increased to 114% (p less than 0.05) and 112% (p = 0.05) of baseline values, respectively. Mean arterial PCO2 in the hypercapnic subgroup of Group B patients decreased from 60 mm Hg before to 52 mm Hg after assisted ventilation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107445 TI - Eicosanoids and lung inflammation. PMID- 3107446 TI - [Severe encephalopathy in a bone marrow transplant in a case of immunodeficiency]. AB - The case of a child with a severe immunodeficiency (purine-nucleoside phosphorylase deficit) in whom an allogenic bone marrow transplant was performed is reported. CT scan showed image suggestive of cerebral infarction. Clinical course and hemostasis alterations suggest a non-bacterial thrombotic endocarditis. Neurologic complications in bone marrow transplant are review. PMID- 3107447 TI - Life-threatening flecainide toxicity. A pharmacodynamic approach. AB - Ventricular tachyarrhythmias and severe bradycardia, flecainide acetate's most serious side effects, occur in patients with chronic heart disease or in healthy persons after frank overdose. Toxic effects appear to correlate closely with drug levels in plasma. The surface electrocardiogram can indicate toxicity by demonstrating this drug's electrophysiologic potency to depress all major cardiac conduction pathways with marked prolongation of the PR and QRS intervals. We report the clinical course of a young, healthy person who developed polymorphous ventricular tachycardia after taking a 3800-mg dose of flecainide acetate. Sinus rhythm was restored without pacing or cardioversion after infusion of a beta sympathomimetic agent, physostigmine, and a sodium load. The initial flecainide serum levels were five times greater than the usual upper therapeutic level. Electrocardiography showed that the lengthened electrocardiographic time intervals decreased in correlation with falling drug levels. Flecainide associated life-threatening arrhythmias and available therapeutic interventions are discussed. PMID- 3107448 TI - Glyburide-induced hepatitis. AB - Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons. PMID- 3107449 TI - Potential "losers" under per-case payment. PMID- 3107450 TI - The lupus anticoagulant: a confusing misnomer. PMID- 3107451 TI - [Lupus anticoagulant and thromboses in scleroderma]. PMID- 3107452 TI - ["Continuity". Progress of a team in today's psychiatry]. AB - Long-term psychiatric treatments still present unsolved problems. They are interesting as far as we do our best to keep them within the general frame of reference in the working practice of our sector. Our aim here, therefore, is not to define a model which could be used everywhere, but mainly to describe the ever questioned research of a team involved in today's psychiatry. That team chose to organise their reflexion around two polarities representing good illustrations of the whole situation as they are faced with everyday: "Crisis" and "Continuity". The purpose of "continuity" is to find out and maintain a therapeutical position which would not oversimplify the difficult problems of psychosis--that is to say avoiding the care to psychotic patients to become a routine. In order to do so, we try to use at their best the current abilities of each team member, whose multi-disciplinary capabilities allow for an individualized and diversified approach; the care-givers also try to maintain a permanent and coherent dialogue between them. This therapeutical stance is time-consuming for all members of the team, but does not require any extra equipment. The point is to organise and maintain the function of a group of caregivers around and together with a specific patient and his environment. Today's psychiatry cannot but raise the question of iatrogenicity in its interventions, of which "Chronicity" might well be one of its end-results. With the "Continuity" concept, we intend to maintain a fairly clear therapeutical relationship both with the patient and his environment, thus preventing, as far as possible, defects in the future. PMID- 3107453 TI - Role of the preoptic area in the neuroendocrine regulation of reproduction: an analysis of functional preoptic homografts. AB - In conclusion, POA grafts that contain GnRH cell bodies are capable of correcting many of the reproductive deficiencies that are associated with a genetic failure to produce GnRH. The previously infertile animals exhibit steroidogenesis and gametogenesis. Ovulations associated with mating suggest that the grafted GnRH cells are responding to some environmental cues and may be under some regulation by the host brain. Although the grafts contain tissue that may have sexually dimorphic characteristics, the studies with the hpg mice have not yet revealed any effects of the grafts that could be related to the sex of the donor. PMID- 3107455 TI - [Biological behavior of Sarcoptes scabiei var. suis in swine epidermis. A scanning electron microscopy study in hyperkeratotic (or Norwegian) scabies of swine]. AB - The behaviour of Sarcoptes scabiei var. suis has been studied in hyperkeratotic scabies of pigs (fig. 1). The scanning electron microscope enabled us to observe the outer surface of the eggs in the burrow and even within the cut body of the fertilized female mite (fig. 2). Early events during hatching of the eggs and the first steps of the newborn larva (fig. 3) are shown. The presence of crystals containing calcium and phosphate is shown to occur in places where huge amounts of faecal material are collected (fig. 4). Although some of these aspects have not been published previously we observed many similarities in behavior between Sarcoptes scabiei var. hominis and suis in their respective hosts affected with hyperkeratotic scabies. As to the therapeutic aspect of scabies in humans, carefully selected drugs currently used in the systemic treatment of scabies in pigs would be worth a trial in patients difficult to treat. PMID- 3107454 TI - Signal transduction in insulin secretion: comparison between fuel stimuli and receptor agonists. AB - The initial events in signal transduction in insulin-secreting cells are summarized in FIGURE 8. Both nutrient stimuli, such as glucose and amino acids and the muscarinic agonist carbachol (carbamylcholine) raise [Ca2+]i. Although the rise in [Ca2+]i precedes the stimulation of insulin release, it is not a moment-to-moment regulator of release. The metabolizable fuel stimuli cause Ca2+ influx through voltage-dependent Ca2+ channels following depolarization of the membrane potential. In contrast, carbachol, which does not depolarize, elicits Ptd Ins 4,5-P2 hydrolysis, a reaction catalyzed by phospholipase C. The generation of Ins 1,4,5-P3 in this instance is Ca2+ independent, but appears to involve a GTP-binding protein. However, this protein is not a substrate for pertussis toxin. The levels of Ins 1,4,5-P3, which releases Ca2+ from an ATP dependent Ca2+ pool of the endoplasmic reticulum, are increased prior to the rise in [Ca2+]i. The mitochondria may take up Ca2+ after large increases in [Ca2+]i. A previously proposed second messenger, arachidonic acid, is much less selective than Ins 1,4,5-P3 in that it releases Ca2+ from mitochondria as well as from the endoplasmic reticulum in a slow and irreversible manner. As Ins 1,4,5-P3 is also generated during glucose stimulation of islets, albeit in a Ca2+-dependent manner, this metabolite could mediate not only the action of carbachol but also contribute to amplifying the [Ca2+]i rise in response to glucose. PMID- 3107456 TI - [Thrombopenia and erythroblastopenia in a 1-month-old infant treated with valproate]. PMID- 3107457 TI - The influence of blood hydrogen ion concentration on the level of consciousness in diabetic ketoacidosis. AB - Among 287 cases of diabetic ketoacidosis, 212 patients were alert, 48 drowsy, 10 stuporous and 17 comatose. The mean blood hydrogen ion concentrations in these 4 groups of patients were 50.0; 72.8; 106.8 and 109.9 nmol/l, respectively. Increased blood hydrogen ion concentration seems to be an important factor in lowering the level of consciousness in diabetic ketoacidosis. PMID- 3107458 TI - [Continuous enteral feeding of the gastrectomized patient with malnutrition]. AB - The development of nutritional parameters, anthropometric and biologic, under polymeric continuous gastro-intestinal feeding, was followed during 3 to 7 weeks in a group of 10 gastrectomised patients with malnutrition and compared with a group of 10 patients with malnutrition secondary to intake deficiencies and receiving the same treatment. Body weight, mid-arm muscle circumference, triceps skinfold and serum transferrin increased significantly from the beginning to the end of the gastro-intestinal feeding in both groups, and in a comparable fashion. Continuous gastro-intestinal feeding is therefore an effective treatment of malnutrition in the gastrectomised patient. The response obtained, as far as nutrition is concerned, may be compared to that of the patient with malnutrition secondary to intake deficiencies. PMID- 3107459 TI - Naloxone reverses the inhibition by sodium valproate of GABA transport across the Deiters' neuronal plasma membrane. PMID- 3107460 TI - Paleoanthropological applications of amino acid racemization dating of fossil bones and teeth. AB - The general principals of the amino acid racemization based dating technique are discussed. The results obtained at Olduvai Gorge (Tanzania) and Zhoukoudian (China) are presented as an illustration of the paleoanthropological application of racemization dating. Tooth enamel provides the best material for the racemization dating of Middle to Lower Pleistocene deposits, although in some cases bones also yield reliable ages. The racemization method provides a means of dating teeth and bones which are too old for radiocarbon dating. Only small samples are required and processing procedures are straightforward. The technique is particularly useful in paleoanthropological studies since hominid fossils can be directly dated. PMID- 3107461 TI - Evaluation of combination chemotherapy in a lightly anesthetized animal model of Pseudomonas pneumonia. AB - Gram-negative bacillary pneumonia is a major cause of morbidity and mortality in hospitalized patients. The use of synergistic combinations of aminoglycosides and beta-lactams for therapy of this infection has been recommended but remains controversial. We designed a new model of Pseudomonas pneumonia in a lightly sedated guinea pig by using a long-acting anesthetic to impair natural respiratory defenses. We used this model to compare the efficacy of ceftazidime and tobramycin alone and in combination in the therapy of Pseudomonas pneumonia. The two antibiotics were shown to be synergistic in vitro for the strain of Pseudomonas aeruginosa tested. Treated animals receiving both antibiotics had fewer viable bacteria remaining in lung tissues (P less than 0.05) and exhibited a trend towards improved survival in comparison to animals receiving a single drug. In this model of Pseudomonas pneumonia, in vitro synergy was reflected by increased efficacy in vivo. PMID- 3107463 TI - Biological activity of analogs of guanine and guanosine against American Trypanosoma and Leishmania spp. AB - The growth inhibitory effects of six guanine and guanosine analogs, 3 deazaguanine (compound 1); 3-deazaguanosine (compound 2); 6-aminoallopurinol (compound 3); 9-beta-xylofuranosyl guanine (compound 4); a ribosylated derivative of compound 3, 6-aminopyrazolo(3,4-d)pyrimidin-4-one (compound 5); and 5 aminoformycin B (compound 6), were tested against some pathogenic members of the family of American Trypanosomatidae. Compounds 1 and 2 were highly active against Trypanosoma cruzi, Trypanosoma rangeli, and American Leishmania spp. in in vitro culture forms. Both compounds also showed antiprotozoal activity in T. cruzi infected mice, with the optimal dose being about 30 mg/kg of body weight per day given as 10 consecutive doses. Compound 3 was the most active compound in vitro, inhibiting all of the American Trypanosomatidae culture forms tested. It was also highly inhibitory in mice that were acutely infected with T. cruzi, with the optimal dose being about 10 mg/kg of body weight per day. Ribosylation of compound 3 resulted in a derivative that showed decreased inhibitory activity on Trypanosomatidae multiplication. Compound 6 was highly inhibitory of in vitro multiplication of American Leishmania and T. rangeli but had no effect on T. cruzi epimastigotes and on mice that were acutely infected with T. cruzi. Compound 4 showed only a slight effect on T. cruzi epimastigotes. PMID- 3107462 TI - Norfloxacin versus thiamphenicol for treatment of uncomplicated gonorrhea in Rwanda. AB - In an open prospective study, single oral doses of norfloxacin (800 mg) and thiamphenicol (2.5 g) were used to treat, respectively, 122 and 46 consecutive patients with uncomplicated gonorrhea. Neisseria gonorrhoeae was eradicated from 119 (97.5%) patients treated with norfloxacin and from 35 (76.0%) patients treated with thiamphenicol. Norfloxacin treatment failure was not related to drug resistance or to insufficient absorption of the drug. Thiamphenicol failure correlated with low in vitro susceptibility of the infecting strain. In a single oral dose of 800 mg, norfloxacin appeared to be an excellent alternative treatment regimen for uncomplicated gonorrhea in an area with a high prevalence of penicillin-resistant gonococci. PMID- 3107464 TI - Enterococcus faecalis hemolysin-bacteriocin plasmids belong to the same incompatibility group. AB - Plasmid pair coexistence was studied both among nine Enterococcus faecalis hemolysin-bacteriocin (Hly-Bcn) plasmids, including pJH2, pAD1, pAM gamma 1, and pIP964, and between pIP964 and five R plasmids. Some of the Hly-Bcn plasmids used were derivatives encoding resistance to erythromycin or tetracycline. The Hly-Bcn plasmids were incompatible with each other; 40 to 100% displacement was observed bilaterally for eight pairs and unilaterally for one pair. In contrast, pIP964 stably coexisted with each of the R plasmids. Entry exclusion was associated with incompatibility for most of the Hly-Bcn plasmids. The nine Hly-Bcn plasmids harbored by E. faecalis form a distinct incompatibility (Inc) group, designated IncHly. PMID- 3107465 TI - Effects of several mycotoxins on specific growth rate of Butyrivibrio fibrisolvens and toxin degradation in vitro. AB - Four strains of Butyrivibrio fibrisolvens did not degrade aflatoxin B1. Acetyl T 2 toxin, T-2 toxin, HT-2 toxin, deoxynivalenol, diacetoxyscirpenol, verrucarin A, zearalenone, and ochratoxin A did not affect the specific growth rate of B. fibrisolvens CE51 significantly, but all were degraded to greater or lesser extents. Breakdown products were produced as a result of deacetylation reactions. PMID- 3107466 TI - Immersible probe for continual monitoring of the population density of microorganisms grown in liquid media. AB - A common technique of measuring population density of microorganisms grown in liquid media is to withdraw a sample of the suspension and measure its apparent optical density with a spectrophotometer. The device we describe is capable of continually and automatically monitoring the population density of microorganisms grown in suspension. PMID- 3107467 TI - Survival of pathogenic bacteria in various freshwater sediments. AB - Four human-associated bacteria, Pseudomonas aeruginosa, Salmonella newport, Escherichia coli, and Klebsiella pneumoniae, were tested for survival in five freshwater sediments. Bacterial survival in continuous-flow chambers was monitored over 14-day periods on sediments ranging from organically rich high clay fractions to organically poor sandy fractions. Bacterial die-off ranged from 1 to 5 orders of magnitude in sediments. E. coli survived as long as or longer than S. newport. P. aeruginosa and K. pneumoniae tended to survive longer than E. coli. Survival of E. coli and S. newport was greater in sediments containing at least 25% clay. Good reproducibility allowed the development of linear models to describe die-off rates. PMID- 3107468 TI - Use of membrane filters for measurement of mycobactericidal activity of alkaline glutaraldehyde solution. AB - Bactericidal assays of 2% alkaline glutaraldehyde solution were carried out using Millipore membranes, and the rate of kill was compared with that of mycobacteria in suspension and on Penicylinder surfaces when using the methods recommended for the official tuberculocidal test. The rate of inactivation observed on the membrane filter surface was similar to that achieved using Penicylinders. The absence of visible colonies on the treated membranes provided a direct demonstration of sterility. The use of filter membranes in tuberculocidal tests provides a simple quantitative assay. PMID- 3107469 TI - Oxygen regulation of nitrate uptake in denitrifying Pseudomonas aeruginosa. AB - Oxygen had an immediate and reversible inhibitory effect on nitrate respiration by denitrifying cultures of Pseudomonas aeruginosa. Inhibition of nitrate utilization by oxygen appeared to be at the level of nitrate uptake, since nitrate reduction to nitrite in cell extracts was not affected by oxygen. The degree of oxygen inhibition was dependent on the concentration of oxygen, and increasing nitrate concentrations could not overcome the inhibition. The inhibitory effect of oxygen was maximal at approximately 0.2% oxygen saturation. The inhibition appeared to be specific for nitrate uptake. Nitrite uptake was not affected by these low levels of aeration, and nitrite reduction was only partially inhibited in the presence of oxygen. The regulation of nitrate respiration at the level of transport by oxygen may represent a major mechanism by which the entire denitrification pathway is regulated in P. aeruginosa. PMID- 3107470 TI - Regulation by forskolin of octopamine-stimulated adenylate cyclase from brain of the dipterous Ceratitis capitata. AB - Forskolin, a diterpene that exerts several pharmacological effects, activates adenylate cyclase in brain and in some other mammalian tissues. Properties of forskolin activation of adenylate cyclase from central nervous system of the dipterous Ceratitis capitata are described. The interaction of forskolin with the insect adenylate cyclase system was studied by evaluating its effect on metal-ATP kinetics, protection against thermal inactivation, membrane fluidity and enzyme modulation by fluoride, guanine nucleotides, octopamine, and ADP-ribosylation by cholera toxin. The diterpene stimulated basal enzyme activity both in membranes and Triton X-100-solubilized preparations, apparently devoid of functional regulatory unit, this effect being rapidly reversed by washing the membranes. An increase of Vmax accounts for the activation of soluble and membrane adenylate cyclase preparations by forskolin, whereas the affinity of the enzyme for the substrate was not affected. Forskolin apparently protects the membrane enzyme from thermal inactivation, and at concentrations that promote the enzyme activity the diterpene does not alter membrane microviscosity. Forskolin does not appear to alter the sensitivity of insect adenylate cyclase to sodium fluoride, guanine nucleotide, or regulatory subunit ADP ribosylated by cholera toxin, the combined effect of these factors with the diterpene resulting in a nearly additive enzymatic activation. However, forskolin blocks the octopamine stimulatory input. Results obtained with the insect adenylate cyclase system are discussed and compared to what is known about mammalian systems to propose a mechanism of enzyme activation by forskolin. PMID- 3107471 TI - In vivo regulation of form I ribulose 1,5-bisphosphate carboxylase/oxygenase from Rhodopseudomonas sphaeroides. AB - When autotrophically grown cells of Rhodopseudomonas (Rhodobacter) sphaeroides were supplied with an organic carbon source, the activity of ribulose 1,5 bisphosphate carboxylase/oxygenase (RuBPC/O) decreased 30 to 60%. The extent of inactivation varied depending on the level of derepression of form I and form II RuBPC/O, and on the nature of the organic carbon source, pyruvate being the most effective. Raising the concentration of CO2 in the gas phase of autotrophic cultures brought about a similar loss of RuBPC/O activity. Immunological assays of form I and form II RuBPC/O proteins indicated that the synthesis of both enzymes had been repressed. Moreover, it is demonstrated that the observed loss of RuBP carboxylase activity was due to inactivation of the form I enzyme; the form II RuBPC/O was not affected. The isolated inactivated form I RuBPC/O exhibited a fivefold lower specific activity compared to the active form I enzyme. The inactivation was accompanied by changes in the properties as well as the structure of the form I enzyme. In autotrophic cells, form I RuBPC/O appeared to be associated with a phosphate-containing compound that decreased the enzyme's relative mobility in nondenaturing gels and increased its density in sucrose gradients. Form I RuBPC/O was released from an apparent complex or aggregate upon in vivo inactivation and/or after in vitro heat treatment. The inactive form I enzyme was found to reactivate in vitro by a slow reaction that was accelerated by heat treatment. However, experiments showed no evidence for in vivo reactivation after cells were reexposed to autotrophic conditions (1.5% CO2 in H2). All these data indicate that R. sphaeroides RuBPC/O activity is controlled at the transcriptional and post-transcriptional levels, through regulatory systems that repress the synthesis of form I and form II RuBPC/O and inactivate the predominant form (form I) when the carbon source no longer becomes limiting for growth. PMID- 3107472 TI - Expression of a functional 78,000 dalton mammalian flavoprotein, NADPH-cytochrome P-450 oxidoreductase, in Escherichia coli. AB - A cDNA containing the complete coding nucleotide sequence for rat liver NADPH cytochrome P-450 oxidoreductase was constructed from two overlapping cDNA clones. This full-length cDNA was inserted into the plasmid expression vector pCQV2, transfected into Escherichia coli, and expressed reductase was identified in cell lysates by electrophoresis followed by electrophoretic transfer to nitrocellulose and immunodetection. Various strains were screened for maximal expression and minimal intracellular degradation of the expressed protein, and strain C-1A was selected for preparation of the expressed enzyme. Induced cells from 12-liter cultures were pelleted, lysed in a French press, and the 50,000g supernate was fractionated by DEAE-cellulose and 2'5'-ADP agarose chromatography. Thirty-five grams of packed cells yielded approximately 2 mg of affinity-purified protein that was essentially free of E. coli proteins. The final preparation exhibited considerable proteolytic degradation and only an estimated 5-10% of the immunoreactive protein was undegraded. Four principal forms could be distinguished upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with molecular weights of 65,000, 66,000, 74,000, and 78,000, the latter being equivalent to that of intact reductase. High-performance liquid chromatography with a Spherogel-DEAE column resolved these forms but resulted in the loss of the 78-kDa form; three peaks eluted with molecular weights of 65,000. Several of the HPLC fractions exhibited cytochrome c reductase activity, indicating correct incorporation of both flavin prosthetic groups, with the 66-kDa form showing the highest specific activity (44 mumol of cytochrome c reduced/mg reductase/min at 22 degrees C). HPLC assay of flavin content demonstrated equimolar FMN and FAD concentrations, and spectrophotometric analysis of the 66-kDa form revealed a spectrum essentially identical to that of reductase purified from rat liver. When the affinity-purified preparation was reconstituted with cytochrome P-450c, rates of benzo[a]pyrene metabolism approaching rates observed with liver reductase were obtained, indicating that the undegraded component in the affinity-purified preparation was able to interact with cytochrome P-450 and catalyze electron transfer from NADPH. PMID- 3107473 TI - Substrate specificity of phosphorylase kinase: effects of heparin and calcium. AB - Phosphorylase b and two peptides with sequences homologous to phosphorylation site 2 (syntide 2) and site 3 (syntide 3) of glycogen synthase were compared as substrates for purified muscle phosphorylase kinase. The substrate specificity of phosphorylase kinase varied according to whether heparin (at pH 6.5) or Ca2+ (at pH 8.2) was used as a stimulator of its activity. Phosphorylase b was preferentially phosphorylated in the presence of Ca2+; the rate of syntide 2 phosphorylation was the same for both stimulators; and the phosphorylation of syntide 3 was completely dependent on the presence of heparin. A kinetic analysis confirmed this stimulator-dependent substrate specificity since both the Vmax and Km for these substrates were affected diversely by heparin and Ca2+. Heparin stimulated phosphorylase kinase maximally at pH 6.5, whereas the effect of Ca2+ was optimal at a pH above 8. However, the stimulator-related substrate specificity could not be explained by the different pH values at which the effects of the stimulators were assessed. Nor did substrate-directed effects by heparin or Ca2+ apparently play a role. No indications were found for a stimulator-dependent specificity in the phosphorylation of sites in protein substrates of phosphorylase kinase (phosphorylase b, the alpha- and beta-subunits of phosphorylase kinase, or glycogen synthase). The diverse substrate specificity of the calcium- and heparin-dependent activities of phosphorylase kinase could be explained in two ways: either by the existence of separate calcium- and heparin stimulated catalytic sites, or by just one catalytic site with two active conformations. The second possibility is favored by the observation that both calcium and heparin stimulated the isolated gamma-subunit (gamma X calmodulin complex) of phosphorylase kinase. PMID- 3107474 TI - Purification and characterization of fatty acid-binding protein from rat kidney. AB - We detected the presence of a fatty acid-binding protein (FABP) in rat kidney cytosols. This protein was eluted and purified 9.3-fold by sequential gel filtration and anion-exchange chromatography. Homogeneity was shown by a single band on polyacrylamide gel with a molecular weight of about 15,500. It had an optimum binding pH of 7.4. The binding of palmitate to the protein was saturable. Examination of fatty acid binding revealed the presence of a single class of fatty acid-binding sites. The apparent dissociation constant was 1.0 microM and the maximal binding capacity was 48 nmol/mg of protein. This protein showed similar binding characteristics for palmitate, oleate, and arachidonate. Rabbit antibody to this cytosolic FABP gave a single precipitin line with the antigen and selectively inhibited [14C]palmitate binding to the protein. PMID- 3107476 TI - [Combined effect of human recombinant interferon alpha, beta and gamma on tumor cell growth and the cell cycle in vitro]. AB - Antiproliferative effect and the effect on cell cycle distribution of human recombinant interferon (rHu-IFN)-alpha, -beta and -gamma in combination on a human colon cancer cell line were investigated in vitro. Combined treatment with rHuIFN-beta and rHuIFN-gamma had a marked antiproliferative effect. Combination of rHuIFN-beta (200U/ml) and rHuIFN-gamma (200JRU/ml) had a similar antitumor effect to rHuIFN-gamma (5,000JRU/ml). From the analysis of the cell cycle obtained by flow cytometry, rHuIFN-beta showed accumulation of the S phase, while rHuIFN-gamma revealed accumulation of the G1 phase. With the combination of rHuIFN-beta and rHuIFN-gamma, G2 + M phase decreased markedly and G1 phase increased. These results suggest that combined treatment with rHuIFN-beta and rHuIFN-gamma can be an effective therapy for human cancer. PMID- 3107475 TI - [Colony-stimulating factor]. AB - The nature, type and mechanism of action of various colony stimulating factors (CSFs) have been described. Among these CSFs, injection of the recombinant human granulocyte CSF (rhG-CSF) caused a marked increase in neutrophils in mice as well as in monkeys. The neutrophilia of injected mice were preceded by a marked increase of hematopoietic precursors in hematopoietic organs. Injection of monkeys with rh granulocyte-macrophage CSF (rhGM-CSF) also induced a marked increase in peripheral blood neutrophils as well as eosinophilia and monocytosis. Injection of recombinant mouse interleukin 3 (rmIL-3) caused a significant increase in peripheral blood eosinophils, neutrophils and lymphocytes. With rmIL 3, however, a remarkable increase was observed in various hematopoietic precursor cells in hematopoietic organs. Both G-CSF and GM-CSF were shown to shorten significantly the period of neutropenia after irradiation and autologous bone marrow transplantation in monkeys. rhG-CSF was demonstrated to accelerate the recovery from neutropenia induced in mice and monkeys by 5-fluorouracil or cyclophosphamide. Human urinary CSF (CSF-HU), which had been reported to stimulate monocyte-macrophage to produce G-CSF, was demonstrated to be effective in accelerating the recovery from neutropenia in patients with various kinds of gynecological and urological malignancies after chemotherapy for their cancers. It also accelerated the recovery from neutropenia after allogenic as well as autologous bone marrow transplantation. These results indicate that CSFs are very effective for the treatment of neutropenia after cancer chemotherapy and bone marrow transplantation. PMID- 3107477 TI - [Lymphocyte cytotoxicity against autologous tumor cells and the effect of interferon-beta on their activities. (2) Evaluation of large granular lymphocytes (LGL)]. AB - Large granular lymphocytes (LGL) were obtained by Percoll density gradient centrifugation of peripheral mononuclear cells from 15 patients with hematological malignancies (10 acute leukemias and 5 non-Hodgkin's lymphomas). Five-hour 51Cr-release cytotoxic assay by LGL was performed against frozen autologous tumor cells in these patients. Mean percentage cytotoxicity by LGL was 5.6%, and this was enhanced to 15.0% by the addition of IFN-beta to the culture medium. A decrease of cytotoxicity was observed when LGL was treated with anti Leu 11b antibody plus complement, or when LGL was pretreated with the unlabelled K562 as a competitive inhibition assay. The addition of monocytes also induced a decrease of cytotoxicity, suggesting that monocytes may act as a suppressive agent in autologous tumor cell killing by LGL. PMID- 3107478 TI - [Clinical results of treatment with the UFT fine granule preparation under cooperative study. Tokyo Cancer Chemotherapy Cooperative Study Group]. AB - We have carried out Phase II study by single oral administration of UFT fine granule preparation consisting of 1-(2-tetrahydrofuryl)-5-fluorouracil(FT-207) and uracil in the molar ratio of 1 : 4. There were 40 evaluable cases out of 54 registered cases, and PR rate was 10.0%. We have observed 2 PR cases out of 14 evaluable cases with stomach cancer, and the response rate was 14.3%. There were PR cases in hepatoma and breast cancer also. Myelosuppression appeared in 10.6% and subjective and objective side effects in 27.1%, in which major symptoms were gastrointestinal disorder similar to those observed in the study of UFT Capsule preparation. We did not observe hepatic and renal malfunctions. PMID- 3107479 TI - [In vivo chemosensitivity test for UFT and FT-207. II. Chemosensitivity test on human tumor xenografts transplanted in nude mice]. AB - The present study was designed to predict the clinical effect of UFT and FT-207 in short-term administration using a nude mouse-xenograft system. Five human tumor xenografts transplanted into nude mice were used. UFT and FT-207 were administered with the LD10 doses orally for seven consecutive days. Tumor size was measured on day 7, 14 and 21 after the administrations. No significant differences in antiproliferative effects were observed between the measurements of tumor size made on day 7 and day 21. UFT inhibited significantly the tumor growth of CH-I established from colon cancer in which the prolongation of life span has been obtained by clinical long-term administration of UFT. These results suggest that this chemosensitivity test system using nude mice is useful for prediction of clinical response at 7 days after final administration of UFT and FT-207. PMID- 3107481 TI - Carbon dioxide lasers: a broader perspective. PMID- 3107480 TI - [Effect of combination of UFT and MMC (UFT-M therapy) on human colonic cancer xenotransplanted into nude mice]. PMID- 3107482 TI - Plasmapheresis in a patient with scleromyxedema. AB - We describe a patient with progressive scleromyxedema who failed to respond to previously described treatment modalities. A trial of plasmapheresis was initiated, but after an initial promising response, his disease continued to progress. The skin involvement appeared to progress even more rapidly after the plasmapheresis was discontinued. PMID- 3107483 TI - Studies with an enthesis index as a method of clinical assessment in ankylosing spondylitis. AB - The histopathological characteristic of ankylosing spondylitis (AS) is the presence of chronic enthesitis. Our aim was to develop a clinical measurement of the severity of tenderness over entheses. The scoring system was based on the patients' response to palpation over entheses easily accessible to examination. The enthesis index (EI) correlated with pain (r = 0.67, p less than 0.01) and stiffness (r = 0.46, p less than 0.05) scores. A single, blind, crossover study was conducted to determine the sensitivity of the index to change in clinical state associated with non-steroidal antirheumatic drug therapy and to record the interobserver variability. The index showed significantly lower scores after one week's drug treatment (p less than 0.05). The EI is a convenient, non-invasive measure of disease severity in patients with AS. Potential applications include the assessment of enthesitis in other polyarthritides and a means of distinguishing clinically between severity of enthesitis and synovitis in different types of polyarthritis. PMID- 3107484 TI - Arachidonic acid and pulmonary function in heart-lung-preparation of guinea-pig: modulation by PCO2. AB - In normocapnic and deeply hypocapnic guinea-pig heart-lung-preparations (HLPs), dose-response relationships were estimated for the bronchoconstrictor and pulmonary hypertensive responses to histamine (H), 5 hydroxytryptamine (5HT), arachidonic acid (AA) and U-46619, a prostaglandin endoperoxide analogue acting on thromboxane (TXA2) receptors. Hypocapnia potentiated in a different way the bronchoconstrictor effects of AA (increased slope of dose-response curve) and of U-46619 (shift to the left of the curve). The pulmonary vascular effects of U 46619 were unaffected by CO2 tension, whereas a linear log dose-dependence of the pulmonary hypertensive responses to AA was present only in hypocapnic HLPs. The amount of TXA2-like material released in normocapnic HLPs was compatible with the AA/U-46619 potency ratio calculated for the bronchoconstrictor responses in normocapnic HLPs and for the pulmonary vascular responses in hypocapnic HLPs. The above described effects of hypocapnia were different from those produced on the bronchial and pulmonary vascular reactivity to H and 5HT, suggesting that specific mechanisms are involved in the modulating effect of PCO2. The inhibition by indomethacin of AA-induced pulmonary vasoconstriction was unaffected by changes in CO2 tension; conversely, the bronchoconstrictor effects of AA were more substantially reduced by indomethacin in normocapnic HLPs. It is concluded that: the relative contribution of different AA metabolites to the final response of the airway system to the precursor is affected by changes in CO2 tension; different receptorial or prereceptorial mechanisms are involved in the CO2-AA interaction taking place in the two components of the lung parenchyma; the pulmonary outflow of AA metabolites provides only circumstantial evidence of the functional meaning of this release. PMID- 3107485 TI - Different sensitivities of arteries and veins to glyceryltrinitrate-induced relaxation and tolerance: an "in vitro" study on isolated vessels from rabbits. AB - Glyceryltrinitrate (GTN)-induced relaxation was examined in helical strips of rabbit femoral and mesenteric vessels after precontraction with norepinephrine (EC-50). Concentration-response curves over a wide concentration range (10(-9) to 3 X 10(-4) mol/l) appeared to be biphasic with a plateau at 10(-6) mol/l. Threshold concentrations for relaxation (EC-10) were different in arteries (2 X 10(-8) mol/l) and in veins (2 X 10(-9) mol/l), indicating a higher sensitivity of veins than of arteries to low concentrations of GTN. After induction of GTN tolerance (60 min preincubation with EC-90) the arterial vessels revealed a monophasic concentration response curve (EC-10: 10(-6); EC-50: 10(-5) mol/l). The relaxation at the lower concentration range was abolished (shift to the right at lower GTN-concentration). On the other hand, in veins the concentration-response curve was completely shifted to higher concentrations (EC-10: 10(-8) mol/l) and the high sensitivity component was diminished to 50%. However, the enhanced sensitivity of veins in comparison to arteries was preserved. 10(-3) mol/l cystein was unable to affect tolerance in arteries, but partially reversed the development of tolerance effects in veins. Moreover, 10(-6) mol/l indomethacin could mimic GTN-tolerance in arteries but not in veins. Thus, relaxation as well as tolerance induced by GTN, seem to be mediated at least by 2 different mechanisms. Only in arteries the prostaglandin system appears to be involved. On the other hand depletion of SH-groups seems to play a major role in veins in agreement with the hypothesis of Ignarro et al. (1981). PMID- 3107486 TI - Heparin resistance induced by intravenous nitroglycerin. A word of caution when both drugs are used concomitantly. AB - Intravenous (IV) nitroglycerin was found to interfere with the anticoagulant effect of heparin during eight infusions of both drugs in seven patients who were closely monitored with frequent activated partial thromboplastin time determinations. All patients were resistant to heparin when receiving IV nitroglycerin and had a marked increase in sensitivity when discontinuing the IV nitroglycerin therapy. This effect was present whether or not propylene glycol was in the preparation. Patients treated with simultaneous IV nitroglycerin and IV heparin must be monitored often to avoid inadequate anticoagulation, and heparin dosage should be decreased when stopping IV nitroglycerin therapy to avoid hemorrhage. PMID- 3107487 TI - Maintenance etidronate in the prevention of malignancy-associated hypercalcemia. AB - Normocalcemic patients with cancer who had been successfully treated for an episode of hypercalcemia were enrolled in a randomized, multisite, double-blind, placebo-controlled trial designed to determine the efficacy of maintenance oral etidronate in preventing the recurrence of moderate to severe hypercalcemia (serum calcium level, greater than 11.5 mg/dL [greater than 2.87 mmol/L]). Ten (40%) of 25 etidronate-treated patients and 17 (46%) of 37 placebo-treated patients had recurrence of hypercalcemia within 150 days. Although patients taking etidronate had a longer time to the development of hypercalcemia (median, 55 days vs 28 days), this was not significantly different from the control group. The high attrition rate in this trial from hypercalcemia and other malignancy related causes represents a major difficulty in conducting studies with agents that may require prolonged administration before producing a therapeutic effect. PMID- 3107488 TI - [Long-term clinical results of the implantable automatic defibrillator]. AB - Between October 1982 and May 1986, 12 patients were implanted with an automatic defibrillator AID-B; 7 had coronary artery disease, 2 had dilated cardiomyopathies and 3 had torsades de pointe with or without long QT intervals. Five patients had a thoracic approach with a left ventricular patch and implantation of a right atrial endocavitary electrode. Thereafter a subcostal approach was used with 2 patch electrodes. Two of the first 5 patients rejected the device, but this complication was not observed in the remaining 7 cases. The threshold of defibrillation was greater than 25 joules in 1 case out of 5 with a patch and endocavitary electrode. This threshold was less than 25 joules in all patients with 2 patch electrodes. The AID-B was triggered in less than 20 seconds. One patient died of pulmonary embolism 8 days after implantation; 2 others had a temporary aggravation of their arrhythmias. There were no cases of inappropriate activation of the AID-B device during follow up: 5 patients had no arrhythmia or defibrillation. The 6 others had 2 to 35 defibrillations with documented arrhythmias before or after defibrillation. One patient suffered a sudden death after exhaustion of the device which had functioned on two occasions but had not been replaced for economic reasons. The technique of implantation has been simplified, so limiting local complications. This device is reliable and represents an effective palliative treatment of sudden death due to ventricular arrhythmias. PMID- 3107489 TI - [Study of sinus function and nodal conduction using transesophageal recordings]. AB - Transoesophageal pacing is mainly used for treatment of supraventricular tachycardias and assessment of refractory periods of accessory pathways. It has been proposed for the study of sinus node function and A-V nodal conduction. The aim of this study was to know if transoesophageal pacing could modify the vago sympathetic tone, therefore the results of the tests, knowing it can be discomfortable and that endodigestive procedures can induce vagal responses. Furthermore, the stimulation is elicited near the left atrium, and not in the right atrium as during endocavitary tests. We have compared in 20 patients (age 68 +/- 12) the results obtained by both endocavitary and transoesophageal pacing (tension 21.2 +/- 4.5 V, duration 16 msec, interelectrode spacing 30 mm). We measured sino-atrial conduction time (SACT), sinus node recovery time (SNRT), Wenckebach's point and nodal refractory periods. After introduction of the oesophageal lead we observed a significant (p less than 0.01) but slight and transitory tachycardia. The results of A-V nodal conduction parameters were not significantly different and were significantly correlated (r = 0.94 for Wenckebach's point and effective refractory period). For the sinus node function, there was no significant difference between the parameters if the oesophago atrial delay (mean 104.4 +/- 25.9 msec) is taken into account. The correlation is poor for sino-atrial conduction time (corrected SACT, r = 0.55), tighter for sinus node recovery time (maximal corrected SNRT, r = 0.92).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107490 TI - [Myocardial metabolism in angina with angiographically normal coronary arteries]. AB - Myocardial metabolism was studied during rapid atrial pacing in 22 patients with angina and angiographically normal coronary arteries. Pyruvate, non esterified fatty acid and lactate levels were measured in the coronary arteries and veins under basal conditions, at the peak of atrial pacing and during the recovery phase. A control group of 8 patients had neither angina, ST depression, or lactate production during atrial pacing. A correlation was observed between the coronary arterio-venous difference and arterial pyruvate and non esterified fatty acid levels in the 22 patients during the 3 periods of study. The control patients did not differ significantly from the rest of the population. There was a correlation between the coronary arterio-venous difference and arterial lactate levels under basal conditions in all of the study and control groups. This correlation remained significant during atrial pacing and the recovery period only in the control group. It was possible to distinguish a group of 14 patients (64 p. 100) (Group A) with a correlation coefficient of lactate production similar to the control group (+/- 2 standard deviations) during atrial pacing, from a second group of 8 patients (36 p. 100) (Group B) with abnormal myocardial metabolism. The arterial lactate concentrations were similar in both groups in the 3 periods of study. A coefficient of lactate extraction less than 10 p. 100 was observed in 2 patients in Group A and in 7 patients in Group B (88 p. 100, p less than 0.01). One patient in Group B had a coefficient of lactate extraction greater than 10 p. 100 (+ 13 p. 100).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107491 TI - [Surgery of Wolff-Parkinson-White: value of the epicardial approach. Apropos of 28 surgically treated cases]. AB - The authors report their experience of 28 cases of the Wolff-Parkinson-White (WPW) syndrome treated by surgery. Four patients had multiple accessory pathways; of the 32 bundles of Kent detected, 16 were in the postero-septal region. Surgery, performed under cardio-pulmonary bypass after epicardial mapping, consisted in atrioventricular disconnection using no special physical agent. With the exception of 2 cases, the left lateral accessory pathways were operated using a classical left intraatrial approach whereas in the right lateral and septal forms the main procedure of dissection of the right atrioventricular groove was carried out by an epicardial approach. There was one operative death due to haemodynamic and haemorrhagic problems in a top class athlete with two bundles of Kent, the interruption of which required two consecutive bypass procedures. In the 27 survivors, 29 of the 30 accessory pathways were successfully interrupted (96 p. 100). The only failure occurred in a patient with two bundles of Kent. On the other hand, in 2 patients, complete atrioventricular block was successfully obtained by surgical section of the His bundle during the same procedure in one case, and by postoperative catheter ablation in the other case in which surgery had failed. There were no cases of accidental permanent atrioventricular block. The results in this series confirm the value of surgery in the treatment of the WPW syndrome, especially in the septal forms which are reputed to be the most difficult but in which the approach is greatly simplified by the initial dissection of the tricuspid ring by an epicardial approach.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107492 TI - [Value of the negative U wave during exercise test in the diagnosis of coronary insufficiency]. AB - In order to determine the value of inversion of the U wave during exercise for the diagnosis of coronary insufficiency, the stress tests of 227 patients were reviewed and confronted with the results of coronary angiography which showed 93 subjects with angiographically normal arteries and 134 subjects with left anterior descending disease; 37 patients had single vessel disease (Group I), 38 had double vessel disease (Group II) and 59 had triple vessel disease (Group III). When compared to the two classical criteria, anginal pain and less than or equal to 1 mm ST depression, inversion of the U wave was more specific: 82.8 +/- 7.6 p. 100 vs 77.4 p. 100 for anginal pain, and 66.7 +/- 9.6 p. 100 for ST depression. The sensitivity of this new sign for the detection of coronary insufficiency was 26.9 +/- 7.5 p. 100 vs 80.6 +/- 6.7 p. 100 for ST depression and 56.7 +/- 8.4 p. 100 for anginal pain. The positive predictive value of U wave inversion on effort was 70.9 +/- 12 p. 100 compared to 77.7 +/- 6.9 p. 100 for ischaemic ST depression and 78.3 +/- 8.2 p. 100 for induced anginal pain. Conversely, in angiographically normal coronary arteries, the absence of U wave inversion had a negative predictive value of 44.8 +/- 7.4 p. 100 compared to 70.5 +/- 9.5 p. 100 for the absence of ischaemic ST changes and 55.4 +/- 8.5 for the absence of anginal pain. These results confirm previously published data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107493 TI - [Gamma-angiography in the diagnosis of akinesia and dyskinesia after myocardial infarction]. AB - A one year prospective double blind trial included all patients with myocardial infarction and clinical, electrocardiographic or radiographic signs of left ventricular aneurysm. All 36 patients underwent ventriculography and radionuclide angiocardiography in the same projections: right anterior oblique, antero posterior, left anterior oblique and left lateral. The angiographic diagnosis of left ventricular aneurysm was based on the finding of a deformation of the ventricular contour persisting in diastole; 22 patients were classified as having a left ventricular aneurysm and the 14 others had akinesia alone. The radionuclide diagnosis of left ventricular dyskinesia was based on the finding of the following 3 criteria in at least one projection: crossing of the systolic and diastolic isocontours; over 4 p. 100 of LV pixels having a negative ejection fraction; the dephased infarcted region having a movement separate from that of the remaining healthy myocardium. None of the clinical criteria of inclusion allowed diagnosis of LV aneurysm when compared with the results of ventriculography. The results of radionuclide and conventional ventriculography correlated 100 p. 100 in the diagnosis of severe contractile abnormalities. When compared with ventriculography, radionuclide angiocardiography had a specificity of 95 p. 100 and a sensitivity of 86 p. 100 for the diagnosis of aneurysm. The only false negative was a non-surgical septal aneurysm. The multiplication of the incidences of examination increases the sensitivity of the results of radionuclide angiography. PMID- 3107494 TI - [Results of valvular replacement in chronic or paucisymptomatic aortic insufficiency. Apropos of 79 patients]. AB - The aim of this study was to assess the outcome of 79 patients operated for chronic, pure, severe aortic incompetence with little or no symptoms (Grades I or II of the NYHA Classification). The average age of the patients was 42 years (range 14 to 76 years) and the average follow-up period was 59.4 months (range 3 to 190 months). The preoperative left ventricular volumes on angiography were: end diastolic volume 224 +/- 47 ml/m2, end systolic volume 121 +/- 39 ml/m2. The ejection fraction was 48 +/- 10 p. 100. Forty two mechanical prostheses and 37 bioprostheses were implanted. There were no operative deaths. The 8 year survival rate was 87 p. 100. Ninety four per cent of the survivors remained asymptomatic; 91 p. 100 have had no thromboembolic complications and 90 p. 100 have not been reoperated. The incidence of myocardial dysfunction was 8.8 p. 100 during this period. The most significant poor prognostic factor was a preoperative ejection fraction of less than 40 p. 100. These results show that early surgery in patients with aortic incompetence and little or no symptoms has a low operative risk and a low incidence of late myocardial dysfunction despite severe left ventricular dilatation with decreased left ventricular function. PMID- 3107495 TI - [Medical treatment of hypertrophic myocardiopathy. Comparison of propranolol and verapamil]. AB - It remains difficult to make a reasoned choice between betablockers and calcium antagonists in the medical treatment of hypertrophic cardiomyopathy. In order to help in making this choice, we compared the effects of 320 mg of propranolol and 480 mg of verapamil, prescribed in a random order for an average period of 2.5 months in 24 patients. In 15 patients the two therapeutic sequences were preceded and followed by a clinical examination and an exercise stress test after withdrawal of all treatment. The overall functional status correlated to oxygen consumption was unchanged by the two drugs, but patients felt better more often with verapamil. These was no significant change in maximal power developed during exercise testing although verapamil increased it by 9 p. 100 throughout with a corresponding increase in oxygen consumption. Two parameters were significantly changed by both drugs: the maximal heart rate fell from 161 +/- 22 to 122 +/- 18 with propranolol, and to 145 +/- 28 with verapamil; the oxygen pulse (equivalent to the systolic index) increased from 10.9 +/- 2.2 to 14.8 +/- 3.9 with propranolol, and to 13.7 +/- 2.4 with verapamil. There were no changes in the blood pressure profiles during exercise. Side effects were observed with both drugs; muscular weakness was the biggest problem with propranolol and sinus node dysfunction with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107496 TI - [Hemodynamic effects of a new alpha-1 antagonist, AR-C 239 administrated in intravenous bolus, in patients with cardiac insufficiency]. AB - A new specific alpha-1 antagonist was studied in 16 patients with left ventricular failure. In Group I (8 patients) the drug was given as a 40 micrograms/kg intravenous bolus, and in Group II (8 patients) at the dose of 80 micrograms/kg. A thermodilution Swan-Ganz catheter, a Millar microtransducer introduced via the femoral artery were relayed to a SYSCOMORAM system to record the systemic artery pressures (SAP), pulmonary artery pressures (PAP), left ventricular pressures, and to calculate cardiac output and systemic and pulmonary arterial resistances (SAR, PAR) over a 30 minute period. In Group I (40 micrograms/kg), administration of AR-C 239 led to a significant decrease in PAP and SAP (-24 +/- 17 p. 100, p less than 0.02) with a fall in time-tension index ( 20 +/- 19 p. 100, p less than 0.05) and a significant increase in LV stroke volume (+23 +/- 12 p. 100, p less than 0.01). At 80 micrograms/kg there was also a fall in LV filling pressures (-29 +/- 25 p. 100, p less than 0.05) and PAP (-38 +/- 28 p. 100, p less than 0.02) and an improvement in LV compliance (Gaaschisk 43 +/- 19 p. 100, p less than 0.01). These results show that AR-C 239 is a powerful vasodilator without secondary beta mimetic effects or influence on LV contractility; it may provide an effective means of treating cardiac failure. PMID- 3107498 TI - [Mitral valve prolapse, simple anomaly or risk disease]. PMID- 3107497 TI - [Major thrombopenia induced by heparin. Practical approach to cardiac surgery under extracorporeal circulation]. AB - Major heparin-induced thrombocytopaenia (HIT) is a condition which is feared more for its thrombotic complications than for the risk of haemorrhage. The platelet count is part of routine surveillance of patients receiving this treatment which must be withdrawn if HIT occurs. The use of heparin remains essential for cardio pulmonary bypass surgery. There are two possible scenarios: The thrombocytopaenia occurs in the postoperative period: the standard heparin may be relayed by oral anti-vitamin K anticoagulants, platelet antiaggregant drugs or by low molecular weight heparin (LMWH). The diagnosis of HIT is made before surgery: three therapeutic attitudes are discussed with respect to the urgency of surgery: surgery is deferred for 6 to 8 weeks to allow the platelet count to return to normal and the responsible circulating antibody to disappear; the use of LMWH providing the tests of platelet aggregation are negative with this product; in addition, there are other problems specific to their use in cardiopulmonary bypass to be considered; blood exchange at the beginning of cardiopulmonary bypass to eliminate the circulating factor responsible and so allow the use of standard heparin during and after the operation: this is the only possible solution in cases with in vitro aggregant activity of LMWH. PMID- 3107499 TI - [Porcine valvular bioprosthesis. Results 6 years later]. AB - Between January, 1977 and December, 1980, 128 porcine bioprostheses were implanted in 109 European patients hospitalized at the Boucicaut hospital, Paris: 47 were aortic valve replacements (AVR), 43 mitral valve replacements (MVR) and 19 dual valve replacements (DVR). The operative mortality rate was 11% (12 patients): MVR 21%, AVR 6.4%, DVR 0%. 3 patients were lost sight of. The mean follow-up period was 59.3 months (3-96 months). The overall survival rate at 6 years, including early deaths, was 74.4 +/- 8%: MVR 66.1 +/- 15%, AVR 84.9 +/- 10%, DVR 68.6 +/- 20%. Eighteen late deaths were reported (3.7% patient-years [PY]), 3 of which were due to the valve (0.6% PY). The probability at 6 years of escaping death due to the valve was 96.3 +/- 4%: MVR 96.9 +/- 4%, AVR 100%, DVR 87 +/- 17%. Complications associated with the valve were observed in 17 patients (3.5% PY); they were: degeneration in 2 (0.8% PY), thromboembolic accident in 2 (0.4% PY), haemorrhagic accident in 4 (0.8% PY), endocarditis in 5 (1% PY) and simple disinsertion in 2 (0.4% PY). The probability at 6 years of escaping a complication due to the valve was 80.7 +/- 10%: MVR 90.4 +/- 13%, AVR 81.8 +/- 13%, DVR 55.3 +/- 35%. The probability at 6 years of escaping death and re operation due to the valve was 88.5 +/- 8%: MVR 96.0 +/- 6%, AVR 87.9 +/- 11%, DVR 60.2 +/- 37%. This study and those already published show that compared with mechanical prostheses, bioprostheses clearly reduce the incidence of thromboembolic and haemorrhagic accidents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107500 TI - [Clinical study of double-chamber stimulation. Apropos of 50 cases followed-up for 1 to 5 years]. AB - The authors report their experience of dual chamber pacing in 29 men and 21 women of mean age 71 +/- 4 years. 35 had sinus node dysfunction associated with node His bundle conduction disorders; 31 presented with neurological symptoms and 4 with heart failure (due to pacemaker syndrome in 1 case). Sinus node dysfunction was diagnosed by surface ECG in 25 cases and after electrophysiological studied in only 10 cases. Fifteen patients had atrioventricular block without sinus node dysfunction: 2 of them were young subjects, 1 had pacemaker syndrome and 12 were actual or potential heart failure patients for whom preservation of the atrial systole was justified. Nine patients presented with neurological symptoms. 43 (86%) had cardiac or arterial disease associated with cardiac rhythm and conduction disorders. The percutaneous single subclavian vein approach was used in 36 cases (78%). 41 active and 9 passive fixation electrodes were utilized. The mean follow-up period was 25 months (12 to 70 months), with a cumulative figure of 1,253 months/patients. Two late re-operations for displacement of the atrial electrode were performed. Dual chamber pacing was abandoned, 14 months on average after implantation, in 9 patients (18%), on account of arrhythmias in 4 of them. Three cases of tachycardia from "electronic re-entry" and 6 cases of supraventricular arrhythmia transferred to the ventricle by the pacemaker were observed. Sixteen patients (32%) died 12 +/- 4 months on average after surgery: 12 (33%) had sinus node dysfunction and 4 (26%) had AV block. Death was caused by a cardiovascular disease in 12 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107501 TI - [Emergency surgical repair of acute aortic arch dissection. Apropos of 14 cases]. AB - Among 70 patients operated upon for acute dissection of the ascending aorta between 1977 and 1984, 14 (age range 40-72 years) benefited from emergency aortic arch repair motivated by the presence in, or extension to, this segment of the portal of entry, or by lesions of the supra-aortic main vessels. The operation was performed under cardiopulmonary bypass in all cases. Cerebral protection was ensured in 9 patients by deep hypothermia alone or with circulatory arrest for a mean period of 5 minutes (7 cases), and in 5 patients by continuous brain perfusion (carotid blood flow 4 ml/kg/min; perfusion pressure 70 mmHg). Repair consisted of ascending aorta replacement combined with gluing of the arch whenever possible, or bevelled resection in the concavity of the arch, or complete aortic arch replacement with reimplantation of the cervico-cerebral vessels when necessary. In every case the gelatin-resorcin-formalin glue was used to reinforce the aortic wall or the areas with sutures. Operative mortality was nil. Hospital mortality was 28.5%. In patients operated upon under deep hypothermia alone or associated with circulatory arrest the main complications were neurological (4 cases) and respiratory (3 cases) disorders; these were responsible for the death of 3 patients. A fourth patient died of mediastinitis. No neurological or respiratory complication occurred in patients who had brain perfusion. The mean follow-up period was 37 months (range 7-84 months). Late mortality was nil. All but one patient (sequelae of paraplegia) are in excellent clinical condition. Post-operative angiography alone or combined with computerized tomography showed satisfactory blood distribution in all cases and no aneurysm formation on the dissected aorta despite a persistent false lumen. PMID- 3107502 TI - [Prognostic value of a new perfusion index calculated from coronarography]. AB - A new perfusion index was determined from the study of the coronary vascular bed in 8 myocardial territories: upper septal, lower septal, upper anterior, lower anterior, apical, lateral, posterior and inferior. Stenosis of a vessel reduces perfusion in all territories fed by that vessel, downstream of the stenosis. The perfusion index is calculated by adding up the lesions in all 8 territories. In a population of 418 consecutive patients who had undergone coronary arteriography in 1972 and 1973, survival was evaluated according to the perfusion index and to those parameters which classically have the greatest influence on survival. The perfusion index came out as the most important prognostic factor since such parameters as the number of stenotic vessels and ventricular kinetics lose their prognostic value when adjusted to that index. According to the perfusion index, the 8-year prognosis is the same as in subjects without coronary disease when the reduction in overall perfusion does not exceed 40%. With a 40 to 79% reduction the death risk at 8 years is 30% whatever the exact percentage in each individual. When perfusion is reduced by 80% the death risk at 8 years rises to 72%. This perfusion index, easy to determine, provides a better evaluation of prognosis than the conventional parameters. PMID- 3107503 TI - [Comparative study of auricular stimulation by transesophageal and endocavitary approach for evaluating sinus and atrioventricular node function]. AB - The purpose of this study was to find out whether non-invasive transoesophageal pacing could effectively replace right intra-atrial pacing for the indirect evaluation of sinus node and atrioventricular (AV) node function. In a population of 17 patients the corrected sinus node recovery time (CSRT), the atrio-sinu atrial conduction time (ASACT) and Wenckebach's point (W) were calculated by intracavitary pacing, then by transoesophageal pacing. There was no significant difference between the two methods in pre-pacing sinus cycle. With right intra atrial pacing, mean CSRT value was 365 +/- 54 ms (with 5 values greater than 520 ms), mean ASACT value was 229 +/- 29 ms (with 8 values greater than 220 ms), and W occurred at a mean cycle length of 425 +/- 29 ms. With transoesophageal pacing, mean CSRT value was 406 +/- 87 ms (with 5 values greater than 520 ms), mean ASACT value was 222 +/- 17 ms (with 8 values greater than 220 ms), and W occurred at a mean cycle length of 408 +/- 26 ms. The two methods correlated very closely for CSRT and W (r = 0.97) and relatively well for ASACT (r = 0.84). The number of CSRT and ASACT values regarded as prolonged was the same with the two methods; 84% of recorded (i.e. maximal) CSRT values occurred with the same length of pacing cycle. There was no statistically significant difference between the two methods in the calculation of CSRT and ASACT, but W occurred at a slightly shorter cycle (p less than 0.05) with transoesophageal pacing. Thus, transoesophageal pacins is a non-invasive, easy to perform method for indirect exploration of sinus node and AV node function in patients who do not require subnodal conduction studies. PMID- 3107504 TI - [Correlation between late surface potentials and inducible ventricular arrhythmias. Apropos of 115 cases]. AB - Programmed ventricular stimulation and a search for late surface potentials (LP) by means of signal-averaging and quantification by Simson's method were performed in 115 patients divided into five groups: group I (n = 50) with no myocardial infarction (MI) and no clinical or induced ventricular tachycardia (VT); group II (n = 28) with MI and no clinical or induced VT; group III (n = 8) with MI, no clinical VT but induced non sustained VT (NSVT); group IV (n = 19) with MI, no clinical VT but induced sustained VT (SVT); group V (n = 15) with clinical and induced VT. The terminal portion of the averaged signal (AS) was analyzed by three parameters: duration of AS terminal portion less than 40 microvolts (Dur TP), AS amplitude 50 and 40 ms before its end (Amp 50, Amp 40). The presence of TP was defined in two ways: criterion A = Amp 40 less than 25 mcv, criterion B = at least two sub-criteria: Dur TP greater than 40 ms, Amp 50 less than 25 mcv, Amp 40 less than 15 mcv. Compared to groups I and II, the AS of group V was characterized by a prolonged and low amplitude terminal portion (p less than 0.001). Groups III and IV were intermediate. The incidence of TP in groups I to V was 20, 28, 37, 56 and 80% respectively with criterion A, and 4, 4, 0, 28 and 66% respectively with criterion B. The lower incidence of TP in group IV as compared to group V was probably due to the induction of purely artefactual SVT's, notably those with rapid cycle (greater than 270 cps/min) which are remarkable on several accounts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107505 TI - [Gallium-67 scintigraphic evaluation of primary dilated myocardiopathies in adults]. AB - Myocardiopathy (MCP) is diagnosed by exclusion in patients with congestive heart failure in the absence of lesions of the coronary vessels or cardiac valves. Endo myocardial biopsies and several cases of clinical improvement under immunosuppressive therapy suggest that it may be due due to an immune mechanism. Gallium-67 is taken up by the myocardium and may be regarded as a scintigraphic marker of myocardial inflammation. It may therefore be used to determine which patients would benefit from immunosuppressants. Our study involved 47 patients (mean age 40.1 +/- 10.2 years) with MCP evidenced by angiography and coronary arteriography. Isotopic ejection fraction (EF) and Ga-67 uptake by the myocardium were evaluated in all cases. A significant Ga-67 uptake was observed in 22 patients, 20 of whom could be divided into two groups: group I received an immunosuppressive treatment (azathioprine plus prednisone); group II did not receive such treatment. A new radionuclide cardiac examination was carried out 5 months after the beginning of treatment. No significant Ga-67 uptake could be detected in either group. Significant improvement of EF was observed in 6 patients of group I and in 2 patients of group II. Four patients had died: 1 in group I and 3 in group II. Thus, a decrease in Ga-67 uptake was noted in all patients 5 months after the initial examination, irrespective of the treatment received, which suggests that this decrease belongs to the natural history of the disease. The effect of immunosuppressive therapy on MCP, therefore, ought to be re-evaluated. PMID- 3107507 TI - [Diastolic coronary prolapse in partial left pericardial agenesis]. AB - A few rare cases of coronary artery stenosis and occlusion have been reported in partial left pericardial agenesis. The authors report a privileged observation of partial left pericardial agenesis associated with an atrial septal defect in which diastolic collapse of the left marginal artery was demonstrated; this chronology was confirmed by synchronous analysis. The peroperative findings may explain the pathogenesis of the coronary disease encountered in this type of malformation, providing a new diagnostic sign of partial left pericardial agenesis. PMID- 3107506 TI - [Treatment of chronic cardiac failure with cadralazine. Short- and medium-term results]. AB - The clinical and haemodynamic effects of a single oral dose of cadralazine were studied in 22 patients with an average age of 64 years presenting with severe chronic cardiac failure. Haemodynamic monitoring during the first 24 hours after oral administration of 30 mg of cadralazine showed a peak increase at the 8th hour of the cardiac index (+ 64 p. 100, p less than 0.001), the systolic index (+ 45 p. 100, p less than 0.001) and the left ventricular work (+ 52 p. 100, p less than 0.001) whilst the systemic and pulmonary arterial resistances decreased by 40 p. 100 (p less than 0.0001) and 30 p. 100 (p less than 0.01) respectively. There was no significant change in heart rate or diastolic pulmonary arterial pressures. The haemodynamic improvement was maintained at the 24th hour (cardiac index + 35 p. 100, p less than 0.01 and systemic arterial resistances - 20 p. 100). These results were confirmed at one month. There were few side effects, none of which necessitated withdrawal of the drug. This study shows the efficacy of a single 30 mg daily dose of cadralazine, an arterial vasodilator, in patients with severe cardiac failure. The treatment was well tolerated over the one month study period. PMID- 3107508 TI - [Lipomatous hypertrophy of the interauricular septum. Morphological and electrocardiographical aspects]. AB - The authors report a case of lipomatous hypertrophy of the interatrial septum diagnosed by echocardiography and confirmed by computerised tomography. The electrocardiogram showed an intra-atrial conduction defect considered to be virtually pathognomonic of this condition. The differential diagnosis and clinical implications of this abnormality, which is usually a fortuitous finding, are discussed in the light of recent publications. A precise diagnosis avoids confusion with other pathologies necessitating specific treatment such as intra atrial thrombi and tumours. PMID- 3107509 TI - [Total pericardectomy. Exceptional treatment for recurrent idiopathic cortico dependent pericarditis]. AB - The authors report a case of definitive treatment of idiopathic relapsing pericarditis by total pericardectomy in the absence of signs of constrictive pericarditis after a 15 month period marked by multiple invalidating recurrences and the development of dependence on corticosteroid therapy. The indications of total pericardectomy must be discussed in these exceptional cases of failure of medical therapy in idiopathic relapsing pericarditis. PMID- 3107510 TI - [Gap, phase III and IV block and supernormal conduction of the right bundle branch]. AB - A recent review of the literature corroborated that several factors explained why supraventricular impulses falling gradually earlier in the cycle could traverse the His-Purkinje system while other impulses occurring later could fail to do so. The present report deals with the coexistence (in the same patient) of three distinct mechanisms whereby progressively more premature impulses could be "unexpectedly" conducted. Phase III left bundle branch block coexisted with the following conduction disturbances in the right bundle branch; late "pseudosupernormal" conduction sandwiched in between periods of phase III and phase IV block; intermediate "pseudosupernormal" conduction resulting from the so called type 2 gap, during which propagation occurred, but with H-V intervals longer than later in the cycle; early "true" supernormal conduction (related temporarily to the end of the T wave) exposed when a premature ventricular beat reached the affected zone in a concealed retrograde fashion. These findings show how, with block late in the cycle, conduction in earlier part of the cycle was not always due to "true" supernormal conduction. PMID- 3107511 TI - Characterization of chromosome and plasmid transformation in Bacillus subtilis using gently lysed protoplasts. AB - Competent cells of Bacillus subtilis were transformed with DNA from gently lysed protoplasts. Significant linkages among markers separated by distances of approximately 2.3% of the total chromosome were found, which have not been detected for conventional transformation. In comparison to previous reports, enhanced plasmid transformation was observed [4.0 X 10(7) transformants per microgram DNA (one transformant per 5 X 10(4) molecules added)], when competent cells were transformed with DNA from lysed protoplasts harboring pUB110. PMID- 3107512 TI - Buoyant density fluctuations during the cell cycle of Bacillus subtilis. AB - A simple rapid method for preparing synchronous cultures of Bacillus subtilis has been used to investigate changes in density during the cell cycle. Asynchronous cells separated on a stepped Percoll density gradient had a mean cell density of 1.117 g ml-1 +/- 0.004. Samples from a synchronous culture exhibited variation (ca. 1.5%) in mean cell density which was greatest at the onset of cell division. An asynchronous control culture showed little variation in density. These results are discussed in relation to previous work on Escherichia coli. PMID- 3107513 TI - [Severe epithelio-exfoliative colitis in infants. I. Clinical data]. AB - Two cases of colitis with neonatal onset are reported. They were characterized by their severity which made early exclusive parenteral nutrition necessary, by the lack of ulcerations visible at endoscopy and of biological inflammatory signs and by an associated neural deafness. In spite of prolonged digestive and corticosteroid treatment, a colectomy had to be performed in both cases. The specificity of the histologic abnormalities of the colon individualizes this severe colitis in infancy. PMID- 3107514 TI - L-deprenyl in Alzheimer's disease. Preliminary evidence for behavioral change with monoamine oxidase B inhibition. AB - Since monoamine neurotransmitter disturbances exist in some cases of dementia of the Alzheimer's type (DAT), monoamine-enhancing drugs may ameliorate some symptoms of DAT. L-Deprenyl is a monoamine oxidase (MAO) inhibitor that is generally free of undesired effects. At low doses (10 mg/d) it selectively inhibits MAO-B, an enzyme whose level is elevated in the brains of patients with DAT who are studied post mortem. At higher doses it has more complex effects, including inhibition of MAO-A plus MAO-B. We administered 10 mg/d and 40 mg/d of L-deprenyl to 17 patients with DAT in a double-blind, placebo-controlled, serial treatment. Total Brief Psychiatric Rating Scale scores decreased significantly during 10-mg/d treatment, with decreases in measures of anxiety/depression, tension, and excitement. Approximately one half of the patients' conditions were judged to be improved clinically, with evidence of increased activity and social interaction along with reduced tension and retardation. Similar but smaller changes were observed during 40-mg/d treatment. The behavioral changes were associated with improvement in performance on a complex cognitive task requiring sustained effort. There were minimal physiologic and side effects. The greater effect of low-dose L-deprenyl therapy suggests that it is the inhibition of MAO B, and not MAO-A, that may be important in the behavioral effects of L-deprenyl administration to patients with DAT. PMID- 3107515 TI - Indirect immunofluorescence technique to detect monoclonal antinuclear antibody. AB - Monoclonal proteins directed against nuclear antigens are extremely rare. We describe the use of a double antibody immunofluorescence technique to document the existence of a monoclonal antibody with nuclear antigen activity. The patient was an elderly woman with a small monoclonal protein, but no evidence of a lymphoproliferative or autoimmune disorder. A homogeneous antinuclear antibody (ANA) prompted further studies to determine whether the monoclonal protein was related to the ANA activity. A double-antibody immunofluorescence procedure is described by which the ANA positivity was shown to be entirely due to a monoclonal IgMK protein. It consists of using fluorescein anti-kappa and rhodamine anti-lambda applied to a section of mouse kidney treated with the patient's serum. Documentation of antigenic specificity of monoclonal antibodies by double antibody fluorescence provides a straightforward method that can be utilized by routine clinical laboratories. PMID- 3107516 TI - Large-artery welding with a milliwatt carbon dioxide laser. AB - Microvascular laser welding can be effectively used in large-diameter artery techniques. The carotid arteries of 12 anesthetized mongrel dogs were exposed. Following heparinization, the carotid arteries were transected, cleaned along their edges, and repaired on the right side by laser and on the left side by suture. The laser-assisted vascular anastomosis (LAVA) required four stay sutures and laser power for welding. Six-week patency for LAVA vs suture anastomosis was 100% vs 92%, respectively. Anastomotic time requirements were less with LAVA (seven vs 25 minutes). Intimal healing for both techniques immediately demonstrated an intraluminal thrombus, which resolved showing complete endothelial repair by four weeks. The laser seal demonstrated little inflammation compared with the giant cell reaction of suture anastomosis. Immediate wall tensions of 6 to 18 X 10(5) dynes/cm2 were tolerated after both techniques. Laser assisted vascular anastomosis of large-diameter arteries is feasible, strong, and associated with minimal inflammation. PMID- 3107517 TI - Arterial regeneration over polydioxanone prostheses in the rabbit. AB - We analyzed histologic, ultrastructural, and functional characteristics of rabbit aortic conduits regenerated over absorbable polydioxanone prostheses. Twenty eight polydioxanone-elicited prosthesis/tissue complexes harvested two weeks to 12 months following implantation were analyzed grossly; photographed; sectioned for light, scanning, and transmission electron microscopy; and studied for compliance, bursting strength, and prostacyclin and thromboxane metabolite contents. No aortic-related deaths or hemorrhages occurred. Smooth regenerated conduits without stenoses were seen in 27 of 28 specimens, with one small aneurysm. Transprosthetic myofibroblast migration and proliferation paralleled the kinetics of macrophage-mediated prosthetic dissolution, which was consequently delayed compared with polyglycolic acid prostheses. Confluent endothelial-like luminal surfaces were present after two weeks. Progressive inner capsular thickening ended after three months at 420 micron. Ex vivo compliance curves resembled arterial elasticity. Regenerated tissue withstood 1200 mm Hg of systolic pressure, and 6-keto-prostaglandin F1 alpha to thromboxane B2 ratios did not differ from normal control specimens. PMID- 3107518 TI - Carbon dioxide vs air in pneumoperitoneum. PMID- 3107520 TI - Species differences of glucuronidation and sulfation in relation to hepatocarcinogenesis. AB - The role of glucuronidation and sulfation in the control of proximal and ultimate carcinogens is briefly reviewed. In accordance with the adopted practice of tumor risk assessment, data from two rodent species (rat, mouse) and man have been compared. Sulfate esters have been established as ultimate carcinogens in 2 acetylaminofluorene, safrole and estragole induced hepatocarcinogenesis. In interspecies comparisons the tumor incidence paralleled sulfotransferase activity (Miller and Miller 1981). Glucuronides are often stable transport forms of carcinogens and in this way determine their organ specificity, for example in 2 naphthylamine-induced bladder carcinogenesis and in colon carcinogenesis produced by 2',3-dimethyl-4-aminobiphenyl. In contrast to sulfotransferase activity certain UDP-glucuronyltransferase activities are differentially inducible by xenobiotics. A 3-methylcholanthrene-inducible phenol-glucuronyltransferase (GT1), present in rat, mouse and man, appears to be part of an adaptive program to detoxify aromatic hydrocarbons. After initiation of hepatocarcinogenesis permanent alterations of these enzymes occur; GT1 is markedly increased whereas sulfotransferase is decreased. Together with changes of other drug metabolizing enzymes these alterations often lead to toxin-resistance of initiated hepatocytes. This phenomenon may facilitate selective growth of initiated hepatocytes and may enhance the probability of multiple hits in their genome. PMID- 3107519 TI - Lack of correlation between formation of reactive metabolites and thymic atrophy caused by 3, 4, 3', 4'-tetrachlorobiphenyl in C57BL/6N mice. AB - The possible role of active metabolites of 3, 4, 3', 4'-tetrachlorobiphenyl (TCB) in causing thymic atrophy was investigated using inbred strains of mice. The generation of reactive species which bind covalently to cellular proteins was used to monitor the formation of active TCB metabolites. The amount of in vitro covalent binding of TCB to proteins by liver microsomes was increased markedly by pretreatment of AHH-responsive C57BL/6N mice with either 3-methylcholanthrene (MC) or TCB itself, although these two inducers were not effective in AHH nonresponsive DBA/2N mice. MC treatment also caused an induction of microsomal TCB-binding activity in all of the (C57BL/6N X DBA/2N) F1 mice. Moreover, among 38 individuals of [(C57BL/6N) (DBA/2N) F1 X DBA/2N] backcross, 23 mice responded to MC with respect to microsomal TCB-binding activity while others did not. These results suggest that the conversion of TCB to protein-bound metabolites is mediated by particular form(s) of cytochrome P-450 which is (are) induced by an Ah receptor mechanism. In order to ascertain whether the active TCB metabolites play a role in causing thymic atrophy, 14C-labeled TCB was administered IP to C57BL/6N mice and the amount of covalent binding of radioactive metabolites to tissue proteins was determined. The in vivo binding was evident in the liver, particularly in the microsomal fraction, on the basis of protein content. In contrast, the thymic proteins contained no measurable amounts of bound radioactivity even when the mice showed marked thymic atrophy. These data suggest that thymic atrophy caused by TCB is not likely to result from the generation of reactive metabolites. PMID- 3107521 TI - DNA damage and repair in mouse liver. AB - The formation of DNA adducts in mouse liver has been demonstrated for numerous chemicals including members of most major classes of carcinogens. Considerably less is known about the persistence and repair of DNA adducts in mouse liver. Likewise, major gaps in present knowledge exist regarding the molecular dosimetry of DNA adducts and their potential for miscoding during continuous exposure to high versus low doses of carcinogens. A prime example of this is 2 acetylaminofluorene (2-AAF), the carcinogen used in the ED01 megamouse study. There are no molecular dosimetry studies on the DNA adducts of 2-AAF, even though such a unique data base exists for the dose-response relationship of mouse liver tumors. Reviewing the pertinent literature, identifying deficiencies, and conducting the required research will hopefully permit a better determination of the relevance of mouse liver tumors to man. PMID- 3107522 TI - Individual differences in DNA repair capacities in man. AB - After metabolic activation of benzo[a]pyrene to the 7,8-dihydrodiol-9,10-epoxide, this ultimate carcinogen preferentially binds to the exocyclic amino group of guanine. In order to investigate possible interindividual differences in the capacity of repair of the DNA adducts formed from benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide, their persistence in freshly isolated lymphocytes of several donors was studied. The results show a surprisingly large interindividual variation in DNA adduct formation and their persistence in freshly isolated lymphocytes. This range included several individuals with an apparent complete lack of repair capability for these adducts. Compared with controls, smokers showed on average a lower initial extent of the DNA adducts formed from benzo[a]pyrene-7,8 dihydrodiol 9,10-epoxide, suggesting induction of inactivating enzymes. However, one of the smokers was an individual with apparent complete lack of repair for the DNA adducts formed from benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide, combining exposure to benzo[a]pyrene with a long persistence of the DNA adducts formed from benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide. The investigation of the DNA repair of methylnitrosourea-induced lesions showed significant interindividual differences in the adaptive response triggered by repeated exposure to the carcinogen, whereas the interindividual variations after single doses were low. PMID- 3107523 TI - Variables influencing DNA-binding in mouse liver. AB - The suitability of certain mouse strains for carcinogenicity testing has been questioned. Some chemicals increase the incidence of liver tumors above a relatively high background, an effect not seen in rats. This raises the question whether species and tissue specific effects are involved which are reflected in the DNA binding of metabolites. DNA binding indices in mouse liver have been determined in only a few instances. They are comparable to those found for rat liver DNA with aniline, benzo(a)-pyrene, butadiene, dimethylnitrosamine, methylnitrosourea and they are lower in the mouse with aflatoxin B1, trans-4 acetylaminostilbene and 2-aminofluorene derivatives. The available data on DNA binding in mouse liver suggest that the same adducts are formed as in rats but that metabolism and repair are variables which can modify the extent of DNA damage. However, the extent of DNA binding does not always correlate with the susceptibility of this tissue to carcinogenesis. But mouse liver is no exception in this respect. It is concluded that the formation of mouse liver tumors in long term studies with genotoxic chemicals indicates tumor initiating potential. In contrast, there are other chemicals such as chlorinated hydrocarbon insecticides which do not bind to DNA to any extent and which are not genotoxic in common short term tests and yet give rise to liver tumors in mice but not in rats. Positive results in long term studies are suggested to indicate promoting properties of such compounds. PMID- 3107525 TI - A history of the Arkansas State Dental Association. PMID- 3107524 TI - The role of necrosis in hepatocellular proliferation and liver tumors. AB - A sequence of events which appear to be common in the development of cancer in all mammalian species includes atrophy, hyperplasia, and neoplasia. Evidence to date suggests that cell death (necrosis) is an integral, perhaps essential, factor in the initiation and maintenance of the process but the extent to which necrosis is involved, and the nature of that participation is unclear. Choline deficient B6C3F1 mice have been used to accentuate and investigate necrosis and the development of liver neoplasia following exposure to aflatoxin B1. The binding of AFB1 to DNA correlates with the level of acute necrosis and the early appearance of foci of alteration and later, tumor development. Adducts of GSH-DNA varied as do other parameters including products of peroxidation, but the relation of these variables to necrosis and cancer are unclear at present. These parameters are currently under study. PMID- 3107526 TI - Arkansas State Dental Association. The histories of our districts. PMID- 3107527 TI - A history of the Arkansas State Board of Dental Examiners. PMID- 3107529 TI - Women in dentistry. PMID- 3107528 TI - Arkansas Dental Journal. PMID- 3107531 TI - A history of the Arkansas State Dental Hygienists Association. PMID- 3107530 TI - A history of the Arkansas State Dental Auxiliary. PMID- 3107532 TI - A history of the Arkansas State Dental Assistants Association. PMID- 3107533 TI - Volume of distribution of phenytoin not altered in storage disease. PMID- 3107534 TI - Decrease in reactive amino groups during oxidation or endothelial cell modification of LDL. Correlation with changes in receptor-mediated catabolism. AB - The monocyte/macrophage appears to be the precursor of many of the lipid-laden cells in atherosclerotic lesions, but the mechanism by which these cells accumulate cholesterol to become foam cells remains unclear. We have previously reported that cultured endothelial cells can modify low density lipoprotein (LDL) in a manner that leads to rapid uptake by the acetyl LDL receptor of macrophages. This modification involves free radical-induced peroxidation of LDL and is accompanied by many changes in the physicochemical properties of LDL including increased electrophoretic mobility, increased density, decreased content of esterified cholesterol, hydrolysis of phosphatidylcholine, and fragmentation of apolipoprotein B. Under conditions highly favorable to oxidation, a similar modification can occur even in the absence of cells. In the present studies, oxidation of LDL simply by exposure to 5 microM Cu++ resulted in a modification that was indistinguishable from that produced by endothelial cells. Moreover, it was demonstrated that LDL oxidation by either method is accompanied by a marked decreased in amino group reactivity, comparable to that seen with the chemical modifications of LDL that lead to recognition by the acetyl LDL receptor. Inhibitors of proteolytic enzymes did not reduce fragmentation of apolipoprotein B during oxidation. The rate of catabolism of intravenously injected oxidized LDL in guinea pigs was very rapid, and over 80% of the degradation occurred in the liver. The studies demonstrate that all of the changes associated with endothelial cell modification of LDL can be attributed to oxidation. The cells can, however, promote oxidation under conditions where it would otherwise occur very slowly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107535 TI - Influence of dietary fats on blood coagulation and prostaglandin production in the common marmoset. AB - Common marmosets were fed a standard marmoset diet (REF) or diets supplemented with 12% (wt/wt) sunflower seed oil (SSO) or sheep fat (SF) for a period of 90 weeks. The values for coagulation indices, clotting time, and Russel viper venom time were consistent with decreased thrombotic tendency of platelets from animals on the SSO diet relative to the low fat, REF diet animals, while an increased tendency to thrombosis was observed with SF-fed marmosets. The SSO- and SF supplemented marmosets showed a significantly reduced thromboxane (TXB2) generation from platelets aggregating to collagen (ASC) relative to the REF group, while at 50 micrograms/ml ASC this difference was maintained only by the SSO group. The SF diet-fed marmosets showed a reduced prostacyclin (measured as 6 keto-PGF1 alpha) generation from incubated aorta relative to the REF or SSO-fed groups, which were not different from each other. A reduced proportion of platelet phospholipid arachidonic acid (20:4, n-6) and increased alpha-tocopherol concentration was consistent with the decreased aggregability and thromboxane generation of platelets from SSO-fed marmosets relative to the REF and SF groups. The SF diet-fed marmosets, on the other hand, showed minimal change in arachidonic acid, alpha-tocopherol or platelet reactivity from the REF group. These differing responses to dietary fats are discussed in relation to the potential for the development of thrombosis and atherosclerosis. PMID- 3107537 TI - Completing the peer review circle. PMID- 3107536 TI - Low density lipoprotein metabolism in human macrophages stimulated with microbial or microbial-related products. AB - To determine whether stimulation of macrophages with products related to, or released as a consequence of, infectious processes could play a role in inducing the formation of foam cells, we studied the metabolism of native and acetylated low density lipoprotein (LDL) by human macrophages stimulated with lipopolysaccharide (LPS), muramyl dipeptide (MDP), polyinosinic:polycytidilic acid (Poly I:Poly C) and gamma-interferon. Cholesteryl ester (CE) synthesis by macrophages stimulated with LPS, MDP and Poly I:Poly C was markedly increased when the cells were incubated with native LDL (p less than 0.05). When incubated with acetylated LDL, LPS-stimulated macrophages showed a depression in CE synthesis (p less than 0.05). When incubated with acetyl-LDL, macrophages stimulated with Poly I:Poly C and gamma interferon showed a significant increase (p less than 0.05) in CE synthesis. The increase in CE synthesis by LPS stimulated macrophages exposed to native LDL and by gamma-interferon-stimulated macrophages exposed to acetylated LDL was paralleled by an increase in cholesterol ester mass. The increase in CE synthesis and accumulation observed in LPS-stimulated macrophages incubated with native LDL seems to be due to an increase in the receptor mediated uptake of LDL. LPS inhibited and gamma interferon activated the expression of the scavenger pathway in human macrophages. This may explain the changes observed in CE synthesis and accumulation when macrophages activated by the above stimuli were incubated with acetylated LDL. In conclusion, activation of human macrophages by some products released during, or as a consequence of, infectious processes led to an increase in CE synthesis and accumulation that may be relevant to the formation of "foam cells". PMID- 3107538 TI - Effects of bursectomy, irradiation, and cyclophosphamide on turkeys vaccinated with CU cholera strain. AB - Turkeys surgically bursectomized, irradiated, and/or injected with cyclophosphamide at 1 day were vaccinated with the live Clemson University (CU) strain of Pasteurella multocida. Bursectomized turkeys vaccinated via drinking water or wing-web puncture at 7 weeks and challenged at 11 weeks had a significantly (P less than 0.05) lower survival rate after challenge than unbursectomized controls. Bursectomized and unbursectomized turkeys vaccinated via drinking water at 7 weeks, revaccinated via the auditory tube at 11 weeks, and challenged at 15 weeks had similar survival rates. The vaccinated bursectomized turkeys had significantly (P less than 0.05) lower levels of serum anti-P. multocida antibody than vaccinated unbursectomized controls. Radiation had no immunosuppressive effect. The immunosuppressive effect of cyclophosphamide was dosage-dependent. Bursectomy and injection of cyclophosphamide in the same turkey were complementary. It was concluded that in young turkeys, the development of immunity to the avirulent CU vaccine is highly dependent upon the bursa of Fabricius, but that as they grow older the bursa is of less importance, particularly if they were vaccinated via a parenteral route, such as in the air spaces of the head. PMID- 3107539 TI - Fowl cholera vaccination of growing turkeys with CU strain via routes other than oral. AB - Turkeys developed a high level of protective immunity and serum anti-Pasteurella multocida antibody when vaccinated with the Clemson University (CU) strain of P. multocida via the following routes: wing-web puncture with the recommended dosage or 1:10 dilution of this dosage, subcutaneous, crop injection, cloacal perfusion of the bursa of Fabricius, and intratracheal. The development of immunity after vaccination via the wing-web puncture and subcutaneous routes was dose-dependent: the lower dosages induced less serum antibody and protective immunity. Immunity was greatest 3 weeks after vaccination via wing-web puncture, although immunity was evident as early as 4 days after vaccination. A high level of antibody and protective immunity with no adverse reactions was induced by vaccinating twice, either by the drinking water followed by a similar dosage parenterally or by a parenteral route followed by the drinking water; these regimens were similar to one vaccination in the drinking water. Vaccination via wing-web puncture and possibly subcutaneous injection and bursal perfusion could be used for flocks with a history of a high mortality after vaccination with the CU vaccine in the drinking water and suspected of being immunosuppressed. PMID- 3107540 TI - Vaccination of turkey breeder hens and toms for fowl cholera with CU strain. AB - Unvaccinated laying breeder hens and semen-producing toms were susceptible to the CU strain of Pasteurella multocida and highly susceptible to a virulent strain of P. multocida. Laying breeders vaccinated with CU strain when environmental temperatures were low ceased egg production during the first week after vaccination and had 29% mortality, whereas those vaccinated when temperatures were moderate had only a 25% decrease in egg production and 17% mortality. Comparable nonlaying breeders vaccinated during moderate temperatures did not die. Although few semen-producing toms died postvaccination and the quantity and quality of semen was not affected, 21.7% developed torticollis. Laying breeders were protected against CU vaccine and challenge with virulent P. multocida if vaccinated every 4 weeks beginning when 7 weeks old. Potential breeders vaccinated before laying with combinations of 3 vaccinations via drinking water, wing-web puncture, or inoculation into the air spaces of the head through the auditory tube were protected against challenge after the onset of laying. However, vaccination via wing-web puncture at 25 weeks of age resulted in abscesses that failed to resolve. The combination of vaccinations most effective in protecting laying breeders was vaccination in the drinking water at 7 and 11 weeks and inoculation into the air spaces of the head at 15 weeks. PMID- 3107541 TI - The effect of light on the sexual behavior of Drosophila affinis. AB - Drosophila affinis is a species whose mating is facilitated by light. Although sexually mature D. affinis males court D. affinis males and females vigorously in the light, they do not perform any of the courtship behaviors in the dark. This lack of courtship is not caused by the males and females being unattractive in the dark, since D. affinis males and females elicit high levels of courtship from Drosophila melanogaster males in light and in darkness. Fertility tests confirmed previous observations that mating occasionally occurs in the dark, suggesting that some D. affinis males are capable of courting in the dark. PMID- 3107542 TI - Contrasting patterns of geographic variation in the cosmopolitan sibling species Drosophila melanogaster and Drosophila simulans. AB - An electrophoretic study was carried out to compare the geographic pattern of genetic variation in Drosophila simulans with that of its sibling species, Drosophila melanogaster. An identical set of 32 gene-protein loci was studied in four geographically distant populations of D. simulans and two populations of D. melanogaster, all originating from Europe and Africa. The comparison yielded the following results: tropical populations of D. simulans were, in terms of the number of unique alleles, average heterozygosity per locus, and percentage of loci polymorphic, more variable than conspecific-temperate populations; some loci in both species showed interpopulation differences in allele frequencies that suggest latitudinal clines; and temperate-tropical genetic differentiation between populations was much less in D. simulans than in D. melanogaster. Similar differences between these two species have previously been shown for chromosomal, quantitative, physiological, and middle-repetitive DNA variation. Estimates of Nm (number of migrants per generation) from the spatial distribution of rare alleles suggest that both species have similar levels of interpopulation gene flow. These observations lead us to propose two competing hypotheses: the low level of geographic differentiation in D. simulans is due to its evolutionarily recent worldwide colonization and, alternatively, D. simulans has a narrower niche than D. melanogaster. Geographic variation data on different genetic elements (e.g., mitochondrial DNA, two-dimensional proteins, etc.) are required before these hypotheses can be adequately tested. PMID- 3107543 TI - Historical effective size and the level of genetic diversity in Drosophila melanogaster and Drosophila pseudoobscura. AB - We report the results of a sequential gel electrophoretic study of protein variation in Drosophila melanogaster and its comparison with D. pseudoobscura. The number of alleles and mean heterozygosity were lower in D. melanogaster than in D. pseudoobscura. On the other hand, geographical populations of Drosophila melanogaster have been shown to be much more differentiated than those of D. pseudoobscura. The results suggest that in D. melanogaster low-frequency alleles have been lost during the colonization process and that major alleles have become differentiated among populations. Population bottlenecks, due to various causes, appear to have played a significant role in the shaping of genetic variation in natural populations of many species. It is proposed that a comparison of genetic variation at homologous gene loci between related species can bring out effects of historical bottlenecks and provide an alternative approach for analyzing causes of genetic variation in natural populations. PMID- 3107545 TI - Cathepsins B and D in rat brain glia during experimentally induced neuropathological defects. An immunocytochemical approach. AB - The lysosome-associated cathepsins B and D were localized by means of immunocytochemistry (peroxidase-antiperoxidase technique) in glial cells of rat brain. A specific reaction pattern of hippocampal neuroglia could be observed after intracerebroventricular application of the neurotoxin kainic acid. After the induction of a focal epilepsy in rats by the implantation of cobalt pellets there was a pronounced immunoreaction of glia near the primary focus as well as the mirror focus. It is concluded that both cathepsins are useful immunocytochemical markers to trace functionally activated glia. PMID- 3107544 TI - The effects of recessive lethal Notch mutations of Drosophila melanogaster on flavoprotein enzyme activities whose inhibitions cause Notch-like phenocopies. AB - The biochemical action of the Notch locus whose mutants cause morphological aberrations in flies, viz., notches of wings and bristle multiplication, has been analyzed by the addition to the food medium of enzyme inhibitors causing phenocopies of Notch and by comparison of enzyme activity patterns of Notch mutants with different degrees of phenotypic expression. Notch phenocopies were induced by inhibitors of enzyme activities in two biochemical pathways: the de novo pyrimidine synthesis by 5-methylorotate (inhibitor of dihydroorotate dehydrogenase) and the choline shunt by amobarbital (inhibits choline dehydrogenase) and methoxyacetate (inhibits sarcosine dehydrogenase). The inhibition of de novo pyrimidine synthesis prevents the production of deoxyuridine-5-phosphate, the substrate for the synthesis of thymidine-5 phosphate via thymidylate synthase, whereas the inhibition of the choline shunt prevents the production of HCHO groups and glycine, both of which are involved in the synthesis of 5,10-methylenetetrahydrofolate, which is a cofactor of thymidylate synthase. It was already known that the inhibition of the latter enzyme in vivo induces Notch phenocopies. Notch mutants with a strong morphological expression show low enzyme activities for dihydroorotate dehydrogenase and choline dehydrogenase. Both are flavoprotein enzymes linked to the respiratory chain. The correspondence between the low enzyme activities in Notch mutants with a strong morphological expression and the phenocopying effect of antimetabolites on these enzymes in the two biochemical pathways involved strongly suggests that the morphological effects of Notch on flies are a consequence of lowered activities of choline dehydrogenase and dihydroorotate dehydrogenase. PMID- 3107546 TI - Effect of prazosin and propranolol on lipoproteins of hypertensive patients. AB - A comparative study between prazosin and propranolol with twenty male patients with mild to moderate essential hypertension was used to study the effects of these antihypertensive agents on plasma lipoproteins, and more specifically high density lipoproteins-2 and Apo A-I. After 4 weeks on placebo, the patients were randomly assigned to prazosin therapy (Group A) and other ten patients to propranolol therapy (Group B) for 8 weeks. Doses required for normalization of blood pressure ranged between 1 to 8 mg/day for prazosin and 20 to 240 mg/day for propranolol. The mean blood pressure was lowered to normal by both drugs. The results indicate that prazosin has no adverse effects on plasma lipids and lipoproteins separated by density gradient centrifugation. In contrast, propranolol increased total plasma triglycerides and decreased high density lipoprotein-2 apoprotein A-I and cholesterol levels by 50% in the group of ten patients. Since low levels of high density lipoproteins have been found to be associated with an increased incidence of coronary artery disease, the data obtained suggest that propranolol may induce significant, potentially atherogenic changes on lipid metabolism in hypertensive patients. PMID- 3107547 TI - Large scale purification of intralumenal alkaline phosphatase from calf intestine by immunosorbent affinity chromatography. AB - Electrophoretically and immunologically homogeneous alkaline phosphatase (AP) can be obtained by a simple and rapid two-step procedure. Step 1: Immunosorbent affinity chromatography using immobilized polyclonal anti-AP-antibodies and elution of the bound enzyme by triethylamine solution, pH 11.4. After affinity chromatography the specific activity of the extracted crude material increases from 3.5 to 793 IU/mg. Step 2: Final purification to a specific activity of 1524 IU/mg by DEAE-cellulose ion exchange chromatography. One investigator is able to purify 100 mg AP within 3 days. The overall recovery is 65%. Methods for characterization and selection of anti-AP-antiserum using immunoinhibition of AP are described. PMID- 3107548 TI - [Detection of low molecular weight trypsin inhibitors in small samples of cartilage, cartilage extracts and synovial fluid by gel diffusion]. AB - The radial diffusion assay is a very useful method for detection of low amounts of proteinase inhibitors in biological materials. The determination of low molecular weight (LMW) inhibitors in the presence of high molecular weight inhibitors is possible by the combination of radial diffusion and ultrafiltration. Using this method LMW trypsin inhibitors could be demonstrated in human articular cartilage, but not in human synovial fluid. In cow, pig and sheep a LMW trypsin inhibitor could be found in both the articular cartilage and in the synovial fluid. On the other hand, a LMW trypsin inhibitor could not be found neither in the canine cartilage nor in the canine synovial fluid. The method allows also the direct determination of LMW trypsin inhibitors in cartilage extracts in the presence of 4 M guanidinium hydrochloride or 6 M urea. Therefore, the method is recommended for direct determination of LMW inhibitors by column chromatographic separations of inhibitors. PMID- 3107550 TI - Human myeloma cells acquire resistance to difluoromethylornithine without overproducing ornithine decarboxylase. AB - An exposure of a human myeloma cell line to 2-difluoromethylornithine the mechanism-based inhibitor of ornithine decarboxylase (EC 4.1.1.17), resulted in a selection of tumor cells readily growing in the presence of 4 mM difluoromethylornithine, a concentration that swiftly halted the growth of the parental cells. Determination of the intracellular polyamines revealed that there were measurable amounts of putrescine and spermidine in the resistant cells. Restriction enzyme analyses of genomic DNA isolated from the resistant cells indicated that the gene dosage for ornithine decarboxylase was not increased to any appreciable extent. Similarly, the accumulation of mRNA was unaltered. The resistant myeloma cells, however, displayed arginase (EC 3.5.3.1) activity that was roughly ten times higher than that in the parental cells. PMID- 3107549 TI - A phospholipase A2 isoenzyme provokes lipoxin B formation from endogenous sources of arachidonic acid in porcine leukocytes. AB - Porcine leukocytes incubated with an isoenzyme of phospholipase A2 (PLA2) (isolated from snake venom) produced several trihydroxytetraene- containing compounds which were derived from endogenous sources of arachidonic acid. The formation of these compounds was dose-dependent with an EC50 of approximately 1.25 X 10(-8) M. At this concentration of the isoenzyme and time of exposure the cells remained viable as determined by the exclusion of trypan blue. The compounds were purified by HPLC and their identities were determined by physical criteria which included U.V. spectrometry, GC/MS and by comparison with both synthetic and authentic materials. The biologically derived compounds proved to be lipoxin B (5S, 14R, 15S-trihydroxy-6, 10, 12-trans-8-cis-eicosatetraenoic acid) and its two structural isomers (8-trans-LXB and 14S-8-trans-LXB). Of interest, only small amounts of lipoxin A and its isomers were found in these incubations. Results of the present study indicate that porcine leukocytes can generate lipoxin B and its isomers from endogenous sources of arachidonic acid. Moreover, they suggest that certain PLA2 isoenzymes may initiate the formation of lipoxins and related compounds. PMID- 3107551 TI - Galactosialidosis: a direct evidence that a 46-kilodalton protein restores deficient enzyme activities in fibroblasts. AB - The intracellular function of a specific protein to protect lysosomal beta galactosidase and neuraminidase activities against proteases in human fibroblasts was studied. Beta-Galactosidase was purified from human placenta to different degrees; a preparation (A) contained also two concomitant proteins, and a highly purified preparation (B) contained only the mature beta-galactosidase. The protein concentrate of the culture medium of normal fibroblasts restored the activities of the deficient enzymes, beta-galactosidase and neuraminidase, in galactosialidosis cells. This effect was inhibited only by the anti-A anti-serum, and not by the anti-B antiserum. A 46-kilodalton protein, secreted from fibroblasts cultured in the presence of ammonium chloride, was detected again only by the anti-A antiserum, and not by the anti-B antiserum. It was concluded that this protein has a function to restore their activities in fibroblasts from galactosialidosis patients after being endocytosed from the culture medium. PMID- 3107552 TI - The inhibition of 3 beta HSD activity in porcine granulosa cells by 4-MA, a potent 5 alpha-reductase inhibitor. AB - Addition of 17 beta-N,N,-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstane-3 one, a potent 5 alpha-reductase inhibitor, to granulosa cell cultures inhibited the FSH-stimulated progesterone synthesis during both the initial 48 h induction period and the subsequent 6h test period in a dose-dependent fashion. Besides being a more potent inhibitor of FSH-stimulated progesterone synthesis than testosterone, 4-MA also synergized with the androgen to inhibit progesterone synthesis. These results indicate that 4-MA has a direct inhibitory action on 3 beta-HSD. PMID- 3107554 TI - Epidermal growth factor stimulates tyrosine phosphorylation of human glucocorticoid receptor in cultured cells. AB - Human breast epithelial HBL100 cells, which bind both epidermal growth factor (EGF) and glucocorticoids, were labelled to steady state specific activity with 32Pi and the glucocorticoid receptor was immunoprecipitated from cell lysates with polyclonal antiserum GR884. Immunoprecipitated receptor was resolved by NaDodSO4-polyacrylamide gel electrophoresis and identified by autoradiography. Immunoprecipitated receptor also was characterized by western blot analysis and affinity labelling with [3H]dexamethasone-21-mesylate. Phosphoamino acid analysis of 32P-glucocorticoid receptor revealed 89% phosphoserine and 11% phosphotyrosine. Treatment of steady state 32Pi-labelled cells with EGF stimulated total and alkali-stable phosphorylation in the 97 kDa receptor band by about 35%. Prior incubation with dexamethasone inhibited EGF stimulated, alkali stable phosphorylation of the 97 kDa glucocorticoid receptor band. PMID- 3107555 TI - Multiple isoforms of ADP-ribosylated G-like proteins from mammalian thyroid membranes. AB - Bovine, canine, and porcine thyroid membrane proteins which were [32P] ADP ribosylated by cholera and pertussis toxin in vitro were analyzed by one and two dimensional polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. These three mammalian species have similar cholera toxin substrates (Mr 42,000 and 48,000) and pertussis toxin substrates (Mr 40,000). Resolution by two dimensional gel electrophoresis of these ribosylated proteins revealed that they each consist of at least 6 distinct polypeptides with similar isoelectric points ranging from approximately 5.5-7.0. PMID- 3107553 TI - Endothelial cell proliferation may be mediated via the production of endogenous lipoxygenase metabolites. AB - Endogenous regulators of endothelial cell proliferation have not been clearly defined. We investigated whether the cyclooxygenase and/or lipoxygenase metabolites are involved in this process, and report that lipoxygenase products can modulate endothelial cell growth. Nordihydroguaiaretic acid--a lipoxygenase inhibitor, inhibited endothelial cell proliferation as well as DNA synthesis. 5,8,11,14-Eicosatetraynoic acid--an inhibitor of both lipoxygenase and cyclooxygenase also inhibited endothelial cell DNA synthesis, while indomethacin- a selective cyclooxygenase inhibitor did not affect cell proliferation or DNA synthesis. While arachidonic acid stimulated DNA synthesis, this effect was completely abolished by nordihydroguaiaretic acid. These results demonstrate that products of the lipoxygenase pathway can affect endothelial cell proliferation. PMID- 3107556 TI - Time-dependent effects of follicle-stimulating hormone on progesterone metabolism by cultured rat granulosa cells. AB - The effects of FSH on the accumulation of endogenous progesterone and 20 alpha hydroxy-4-pregnen-3-one as well as on the metabolism of [4-14C]progesterone were studied in 24, 48 and 72 h cultures of rat granulosa cells. FSH stimulated the accumulation of both progesterone and 20 alpha-hydroxy-4-pregnen-3-one by 6-18 fold and 2.5-44 fold, respectively. Short term exposure (24 h) to FSH resulted in the ratio of progesterone to 20 alpha-hydroxy-4-pregnen-3-one accumulations significantly increased (by 2.6 fold), while the reverse was observed for the longer (48 and 72 h) cultures whereby control levels of the ratio of progesterone to 20-alpha-hydroxy-4-pregnen-3-one were significantly greater (by 50% and 270%, respectively) than those of FSH-treated cultures. Effects of FSH on [4 14C]progesterone were also time-dependent. Twenty-four hour cultures were associated with FSH induced inhibition of 20 alpha-reduced metabolites of progesterone (by 55%) while the 48 and 72 h exposures to FSH resulted in a significant increase of the 20 alpha-reduced metabolites above control levels (by 73% and 230%, respectively). Consequently, it is postulated that FSH may exert biphasic time-dependent actions on 20 alpha-hydroxysteroid dehydrogenase activity with short term inhibitory and longer term stimulatory effects. PMID- 3107557 TI - Drosophila melanogaster contains a set of polypeptides capable of polymerizing into intermediate-like filaments. AB - A partial purification scheme applied to the Triton X-100 insoluble pellet of adult flies homogenates yielded a fraction which upon polymerization reproducibly produces filaments which in the electron microscope have all the typical properties of intermediate filaments. This is the first report of the presence of protein components with such properties in Drosophila. Thus, it is highly possible that insects and arthropodes, like other lower invertebrates, may contain the third extremely insoluble element of the cellular cytoskeleton. PMID- 3107558 TI - Synthesis of alkyl-ether glycerophospholipids in rat glomerular mesangial cells: evidence for alkyldihydroxyacetone phosphate synthase activity. AB - We studied the ability of rat glomerular mesangial cells and their microsomal fractions to incorporate 1-[14C]hexadecanol to glycerophospholipids via an O alkyl ether linkage and assessed the presence and activity of the required enzyme: alkyl-dihydroxy acetone phosphate synthase. Suspensions of cultured mesangial cells incorporated 1-[14C]hexadecanol to the phosphatidyl ethanolamine and phosphatidyl choline lipid pools, via a bond resistant to acid and base hydrolysis. When cell homogenates or microsomal fractions were incubated with palmitoyl-DHAP and 1-[14C]hexadecanol, alkyl-DHAP and 1-O-alkyl glycerol were formed (alkyl:hexadecyl). The activity of the enzyme responsible for the O-alkyl product formation was calculated to be 2.5 +/- 0.3 and 544 +/- 50 pmoles/min/mg protein for mesangial cell homogenates and mesangial cell microsomes, respectively. These observations provide evidence that mesangial cells may elaborate either linked lipid precursors de novo for the biosynthesis of O-alkyl glycerophospholipids. PMID- 3107559 TI - Phospholipase A2 activation in chemotactic peptide-stimulated HL60 granulocytes: synergism between diacylglycerol and Ca2+ in a protein kinase C-independent mechanism. AB - In dimethylsulfoxide-differentiated HL60 granulocytes, the chemotactic peptide N formyl-Met-Leu-Phe (FMLP) augments arachidonic acid (AA) release via phospholipase A2 activity induced by the Ca2+-ionophore, A23187. Evidence indicates that this augmentation is mediated by diacylglycerols formed endogenously during FMLP receptor activation: The augmentation is mimicked by the synthetic diglyceride 1-oleoyl-2-acetyl-glycerol (OAG) and the tumor promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate; Pertussis toxin inhibits FMLP induced augmentation but not OAG-induced augmentation: At suboptimal concentrations FMLP and OAG act cooperatively to augment ionophore A23187-induced AA release but not at optimal concentrations. These data indicate that phospholipase A2 activation in FMLP-stimulated HL60 granulocytes involves cooperative interactions between diacylglycerol formed endogenously and Ca2+. Interestingly, this effect of diacylglycerol appears not to be mediated by protein kinase C, since a specific protein kinase C inhibitor, 1-(5 isoquinolinylsulfonyl)-2-methylpiperazine (H7) does not inhibit receptor-mediated release of AA by stimulated HL60 granulocytes. PMID- 3107560 TI - Thrombin-induced transfer of arachidonic acid in human platelets is not inhibited by trifluoperazine. AB - Human platelets have been shown to contain a Ca++- and CoA-independent transacylase enzyme that catalyzes the transfer of arachidonic acid from phosphatidylcholine (PC) to lysoplasmenylethanolamine. It has been suggested that this route may represent a major source for released arachidonic acid in stimulated platelets. In this study, we have shown using arachidonic-labelled human platelets that the thrombin-induced activation of a transacylase reaction was not affected by concentrations of trifluoperazine (TFP) (15 micrograms/2 X 10(9) cells) which abolished the accumulation of free [3H]arachidonic acid in the presence of the cyclooxygenase/lipoxygenase inhibitor BW755C. TFP, at this concentration failed to block the hydrolysis of phosphatidylcholine (PC) completely and had no effect on the increased radioactivity seen in total phosphatidylethanolamine (PE) (160% of control after 4 min of incubation). These results suggest that the transacylase pathway activated in response to thrombin is not likely dependent on calcium. As TFP blocks effectively both the accumulation of free [3H]arachidonic acid and the mass of arachidonic acid without affecting the transfer of this fatty acid from PC to PE in thrombin stimulated human platelets, it is very unlikely that the transacylation pathway represents a major source of release arachidonic acid. Based on these findings, we conclude that the above pathway may be primarily involved in the turnover of plasmenylethanolamine lipids in stimulated human platelets. PMID- 3107561 TI - Biochemical and genetic evidence for distinct membrane-bound and cytosolic sialic acid O-acetyl-esterases: serine-active-site enzymes. AB - A cytosolic sialic acid-specific O-acetyl-esterase was previously described that can remove O-acetyl esters from the 9-position of sialic acids. We show that rat liver Golgi vesicles contain a distinct sialic acid-esterase located within the lumen of the same vesicles that add O-acetyl esters to sialic acids. Studies of a retinoblastoma cell line genetically deficient in the cytosolic enzyme also confirm the existence of distinct membrane-associated sialic acid esterase activity. We developed a sensitive, specific and facile assay, which measures release of [3H]acetyl groups from [3H-acetyl]9-O-acetyl-N-acetylneuraminic acid. Using this assay, we show that rat liver membranes may contain different sialic acid O-acetyl-esterases. The membrane-associated enzyme(s) bind to Concanavalin A Sepharose, whereas the cytosolic enzyme does not. Membrane-bound and cytosolic esterases are inactivated by di-isopropyl-fluorophosphate, showing they are serine-active-site enzymes. PMID- 3107562 TI - The actions of interferon and antiinflammatory agents of induction of indoleamine 2,3-dioxygenase in human peripheral blood monocytes. AB - Interferon substantially induced indoleamine 2,3-dioxygenase and increased L tryptophan metabolism in human peripheral blood monocytes. The induction of dioxygenase by gamma-interferon was significantly higher than that observed with alpha-interferon. This cytokine-dependent induction of the enzyme was markedly and differentially altered by antiinflammatory drugs (i.e., acetaminophen, 3 deazaadenosine, indomethacin and dexamethasone). Dexamethasone potentiated the effect of gamma-interferon and resulted in "super-induction" of the enzyme. This is the first demonstration of the interferon-elicited induction of the dioxygenase in the cells of the immune system and of a novel mechanism for regulating tryptophan metabolism in the cells. PMID- 3107563 TI - GDP beta S enhances the activation of phospholipase C caused by thrombin in human platelets: evidence for involvement of an inhibitory GTP-binding protein. AB - Guanosine 5'-O-thiotriphosphate (GTP gamma S) and thrombin stimulate the activity of phospholipase C in platelets that have been permeabilized with saponin and whose inositol phospholipids have been prelabeled with [3H]inositol. Ca2+ has opposite effects on the formation of [3H]inositol phosphates induced by thrombin or GTP gamma S. While the action of GTP gamma S on the formation of [3H]inositol phosphates is inhibited by Ca2+, action of thrombin is stimulated by Ca2+. Guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), which inhibits the function of GTP-binding proteins, also inhibits the effect of GTP gamma S on phospholipase C stimulation but, surprisingly, increases the effect of thrombin. Ca2+ increases the inhibitory effect of GDP beta S on GTP gamma S activation of phospholipase C, but Ca2+ further enhances the stimulatory effect of GDP beta S on the thrombin activation of phospholipase C. This indicates that two mechanisms are responsible for the activation of phospholipase C in platelets. A GTP-binding protein is responsible for regulation of phospholipase C induced by GTP gamma S, while the effect of thrombin on the stimulation of phospholipase C is independent of GTP binding proteins. However, the effect of thrombin may be modulated by the action of an inhibitory GTP-binding protein. PMID- 3107564 TI - Antigen-and ionophore-stimulated synthesis of platelet-activating factor by the cloned mast cell line, MC9. AB - MC9 mast cells stimulated by a soluble (calcium ionophore A23187) or by an Fc epsilon-receptor agonist (IgE plus hapten) produce platelet activating factor (PAF). MC9 cells incorporate either exogenous [3H]acetic acid or [3H]lyso-PAF into PAF. PAF was identified by mobility on thin layer chromatography, platelet aggregatory activity inhibitable by known PAF antagonists, and by enzymatic modification. Quantified by aggregation of rabbit platelets, MC9 cells produce 6 pmoles PAF/10(6) cells. MC9 cells express acetyltransferase activity of 0.19 nmole/5 min-mg protein. Analysis of MC9 phospholipids by HPLC showed that MC9 cells contain large amounts of phosphatidylcholine (82 nmoles/10(7) cells) but contain little ether-linked phosphatidylcholine (4 nmoles/10(7) cells). PMID- 3107565 TI - Active metabolism of phosphatidylethanolamine plasmalogen in stimulated platelets, analyzed by high performance liquid chromatography. AB - To investigate the stimulus-linked metabolism of platelet phosphatidylethanolamine plasmalogen (PEP) which is not separable from diacyl PE by conventional methods, phospholipids extracted from stimulated platelets prelabelled with 3H-arachidonate (AA) were analyzed by high performance liquid chromatography (HPLC) reported by us (Thrombos. Res. 36, 335, 1984 & 42, 461, 1986). When washed human platelets were stimulated by thrombin or A23187, the amount of PEP monitored by optical density was significantly decreased in consort with phosphatidylcholine (PC), indicating an active participation of PEP in the liberation of AA. Unlike other major phospholipids, PEP hardly incorporated 3H-AA in the resting state but upon stimulation gradual but significant uptake of 3H-AA by PEP was observed. The amount of uptake was not affected by the level of cytosolic free Ca2+ or by the amount of liberated AA, ruling out a direct participation of this unique reacylation process as negative feed back system. PMID- 3107566 TI - Production of 5-formyluracil from thymine in an in vitro active oxygen-generating system. AB - Thymine was placed in a model active oxygen-generating system containing ferrous sulfate, EDTA, and ascorbic acid. The oxidative products of thymine were separated by Sephadex LH-20 chromatography and a reversed phase high-performance liquid chromatography (HPLC) into at least five major components. One of them had a UV spectrum characteristic of 5-formyluracil and mass spectrometric analysis of this material also indicated this material to be 5-formyluracil. PMID- 3107567 TI - Intracellular aflatoxin B1-binding proteins in rat liver. AB - Intracellular aflatoxin B1 binding in rat liver was studied under both in vitro and in vivo conditions. Binding in vivo appeared similar to that observed in vitro except that some covalent adduct formation was detected. Participation of previously described carcinogen-binding proteins such as the Ah receptor, h2-5S protein, 4-5S receptor for 3-methylcholanthrene and the Z-protein fraction was discounted on the grounds of competition binding studies and gel-permeation chromatography. The molecular weight of 45,000 was estimated for the major aflatoxin B1-binding component. Aflatoxin B1 co-eluted with the glutathione S transferases during gel-permeation and separation of the various isozymes by cation-exchange chromatography indicated interactions with the YaYa and YaYc forms. These proteins, however, account for less than 20% of the total intracellular aflatoxin binding. A protein of apparent monomeric structure appears to form the major in vitro/in vivo complex with aflatoxin B1. PMID- 3107569 TI - Initial studies on the cellular pharmacology of 2',3'-dideoxyadenosine, an inhibitor of HTLV-III infectivity. PMID- 3107568 TI - A heterogeneous beta-D-glucosidase activator from monkey parotid gland and its use as an affinity ligand in the purification of human salivary beta-D glucosidase. AB - We have isolated a heat-stable, low molecular weight activator peptide(s) from monkey parotid gland that specifically activated human salivary beta-D glucosidase. This activator appeared to be heterogeneous on Sephadex G-25 gel filtration and polyacrylamide gel electrophoresis under non-denaturing conditions. About 45% of the human salivary beta-glucosidase could bind to the activator immobilised on Sepharose and be eluted by Cutscum. The purified enzyme was nearly homogeneous, with a subunit Mr of 46,000 as revealed by SDS-gel electrophoresis and silver staining. PMID- 3107570 TI - The possible involvement of the phospholipid phase of membranes in mediating the effects of verapamil on Ca2+ transport. AB - The effect of verapamil in a model system of A23187-induced Ca2+-uptake into liposomes was studied. This was done in order to separate the effects of verapamil on the lipid phase of membranes from its effects on membraneous proteins. In the absence of A23187, the liposomes exhibited a very low Ca2+ permeability, which did not change with addition of verapamil. Creation of a valinomycin-induced negative inside membrane potential combined with increased membrane permeability to Ca2+ (A23187), increased Ca2+-entry fivefold and more. Addition of verapamil under these conditions led to a further increase in Ca2+ entry. The negative inside polarization of the liposomes' membrane (as estimated from [3H]TPP+ uptake) was not affected by verapamil. [3H] Verapamil bound specifically to native synaptic plasma membranes with a Kd = 87.4 nM +/- 21.5 (SD) and Bmax = 2.19 pmol/mg protein +/- 0.92 (SD). Specific binding to the liposomes could not be demonstrated. High nonspecific binding of up to about 20% of the total verapamil in the external solution was observed (3.8 pmoles [3H]verapamil/mg phospholipid when 30 nM verapamil was used and 50 nmoles/mg phospholipid when 200 microM [3H] verapamil was used). The high nonspecific binding of verapamil to the liposomes had no detectable effect on the fluidity of their membrane, as seen in fluorescence-anisotropy studies with the fluorescent probe DPH. PMID- 3107571 TI - Identification of 12-keto-5,8,10-heptadecatrienoic acid as an arachidonic acid metabolite produced by human HL-60 leukemia cells. AB - An unusual cyclooxygenase-derived metabolite of arachidonic acid has been shown to be produced by N,N-dimethylformamide (DMF)-induced, terminally differentiated human HL-60 promyelocytic leukemia cells and to a much lesser extent by untreated cells. Biochemical evidence in conjunction with gas chromatography/mass spectrometry and liquid chromatography/thermospray mass spectrometry analyses indicates that the product is 12-keto-5,8,10-heptadecatrienoic acid (KHT). Both KHT and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) were produced when arachidonic acid was incubated with cell lysates obtained from differentiated HL 60 granulocytes. Indomethacin and the thromboxane synthetase inhibitor UK-38485 inhibited the production of both metabolites, whereas ethacrynic acid inhibited only the production of KHT. In 100,000 g supernatant fractions, obtained from either untreated or differentiated cells, KHT was produced when HHT was used as substrate. The addition of exogenous NAD, but not NADP, to incubations caused a significant increase in the production of KHT coincident with a decrease in the level of HHT. These data suggest that, in both differentiated and undifferentiated HL-60 cells, an NAD-dependent enzyme, apparently 15 prostaglandin dehydrogenase (15-PGDH), is expressed and catalyzes the conversion of HHT to KHT. In differentiated HL-60 cells, this metabolite is produced from arachidonic acid through a multi-enzymatic process involving the activities of cyclooxygenase, thromboxane synthetase and 15-PGDH. The production of KHT from arachidonic acid in undifferentiated HL-60 cells is probably limited, therefore, by the virtual absence of cyclooxygenase activity in these cells. PMID- 3107572 TI - Involvement of pentylenetetrazole in synapsin I phosphorylation associated with calcium influx in synaptosomes from rat cerebral cortex. AB - To determine precisely how pentylenetetrazole (PTZ) is involved in the biochemical processes at the presynaptic nerve terminal, the effect of PTZ, under various conditions, on the phosphorylation of synapsin I (previously called protein I) was investigated, using 32Pi in synaptosomes from rat cerebral cortex. PTZ markedly stimulated the incorporation of 32P into this protein as determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and autoradiography, but it failed to stimulate protein phosphorylation in Ca2+-free medium containing ethylene glycol bis-(beta-aminoethylether)-N',N'-tetraacetic acid (EGTA). Moreover, the PTZ-stimulated synapsin I phosphorylation was reversed by addition of EGTA sufficient to chelate all external free Ca2+. PTZ also stimulated synaptosomal accumulation of Ca2+. The PTZ-stimulatory effects of both synapsin I phosphorylation and synaptosomal accumulation of Ca2+ were inhibited markedly by tetrodotoxin as well as by cobalt chloride and lanthanum chloride. The calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W 7, strongly) and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5, weakly) reduced the PTZ-stimulatory effect on synapsin I phosphorylation by about 75 and 15%, respectively, whereas these antagonists had essentially no effect on PTZ stimulated synaptosomal accumulation of Ca2+. These results suggest that PTZ causes the influx of Ca2+ into the presynaptic nerve terminal secondary to the elevated Na+ and is consequently involved in the synapsin I phosphorylation step, facilitating the Ca2+/calmodulin-mediated presynaptic event leading to seizure discharge. PMID- 3107573 TI - Experiments on the mode of action of piriprost (U-60,257), an inhibitor of leukotriene formation in cloned mouse mast cells and in rat basophil leukemia cells. AB - We studied the effect of piriprost, an inhibitor of sulfidopeptide leukotriene (LT) formation, on the generation of the known products of the 5-lipoxygenase pathway of arachidonate metabolism in calcium ionophore A23187-challenged rat basophil leukemia cells and cloned, growth factor-dependent, mouse mast cells. Piriprost inhibited the formation of 5-hydroxyeicosatetraenoic acid (5-HETE), and LTB4, and the sulfidopeptide leukotrienes (LTC4 in the mouse mast cells and both LTC4 and a mixture of LTD4 and LTE4 in the rat basophil leukemia cells) in parallel (IC50 values ranged between 9 and 14 microM for the mouse mast cells and between 15 and 50 microM for the basophil leukemia cells). Our previous observation that piriprost is only a very weak inhibitor of the solubilized LTC synthase of rat basophil leukemia cells was extended to similar enzyme preparations derived from the mouse mast cells (IC50 1.5 mM). The results are consistent with the conclusion that piriprost acts as an inhibitor of the 5 lipoxygenase reaction and that its activity in intact cells is not likely to involve the inhibition of the LTC synthase. PMID- 3107574 TI - Lethal and sublethal effects of the combination of doxorubicin and the bisdioxopiperazine, (+)-1,2,-bis (3-5-dioxopiperazinyl-1-yl) propane (ICRF 187), on murine sarcoma S180 in vitro. AB - Doxorubicin and the bisdioxopiperazine, ICRF 187, synergistically inhibit proliferation of murine sarcoma S180 cells in vitro. Cell cycle analysis was employed to help discriminate cytokinetic from lethal effects of the drug combination. Twenty-four-hour incubation with either agent produced dose dependent partial G2M arrest. At high doses, ICRF 187 produced partial G2M arrest, inhibition of cell division, and continued DNA synthesis at a higher ploidy, resulting in a second G2M arrest of an 8n population. The addition of ICRF 187 to doxorubicin resulted in enhancement of cell cycle blockade at G2M. The combination also produced enhanced lethality as measured by reduced colony forming efficiency of drug-treated S180 cells. Measurement of [14C]doxorubicin accumulation in, and effux from, ICRF 187 pretreated cells failed to reveal an effect of pretreatment with the bisdioxopiperazine on anthracycline disposition by S180 cells, suggesting that the enhanced cytotoxic and cytostatic effects do not result from increased intracellular concentrations of doxorubicin. The positive interaction between the two drugs may represent site-specific enhancement of the anthracycline effect by ICRF 187 at an intracellular target site. PMID- 3107575 TI - Stimulation by vasoactive intestinal polypeptide of catecholamine synthesis in isolated bovine adrenal chromaffin cells. Possible involvement of protein kinase C. AB - In isolated bovine adrenal medullary cells, vasoactive intestinal polypeptide (VIP) stimulated 14C-catecholamine synthesis from 14C-tyrosine, but not from 14C DOPA. This stimulatory effect of VIP on 14C-catecholamine synthesis was not dependent upon extracellular Ca2+. VIP did not affect the intracellular cyclic AMP (cAMP) level. The stimulatory effect of VIP on 14C-catecholamine synthesis was additive with that of carbamylcholine, which was dependent upon extracellular Ca2+, but not with that of phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of protein kinase C. Moreover, 1-(isoquinolinyl-sulfonyl)-2 methylpiperazine (H-7), an inhibitor of protein kinase C, inhibited not only TPA stimulated, but also VIP-stimulated 14C-catecholamine synthesis from 14C tyrosine. These results suggested that VIP stimulated catecholamine synthesis by activation of tyrosine hydroxylase and that protein kinase C was involved in this stimulatory mechanism. PMID- 3107576 TI - [Determination of beta-galactosidase activity on nitrocellulose plates using 5 bromo-3-indolyl-beta-D-galactopyranoside and tetrazolium salts]. AB - A simple and convenient technique has been developed for detection of beta galactosidase from E. coli on nitrocellulose sheets using a mixture of 5 bromoindol-3-yl-beta-D-galactopyranoside and nitro blue tetrazolium, which enables rapid detection of fmole (10(-15) mole) quantities of the enzyme at pH 9.5. The technique has the following advantages: the substrates are stable for a long period; reaction products give non-fading intense blue colour, resolution is extremely good with essentially no diffusion. PMID- 3107577 TI - Anticardiolipin antibodies in patients with systemic lupus erythematosus. AB - We studied a group of 59 unselected patients with systemic lupus erythematosus (SLE); these patients were from a defined population who lived in southern Sweden. We found that serum concentrations of anticardiolipin antibodies were increased in 32 SLE patients (54.2%). No significant correlation between increased amounts of anticardiolipin antibodies and clinical symptoms, such as thrombocytopenia or thrombosis, was found. Serial serum samples from 28 patients (12 patients were from the epidemiologic cohort) were analyzed. Sixteen of these 28 patients (57.1%) had increased levels of anticardiolipin antibodies; in most cases, there was no variation in these values with regard to clinical disease flares or treatment. Increased concentrations of anticardiolipin were observed in 4 patients with cerebral infarction. However, very high concentrations of anticardiolipin antibodies were observed in several patients with inactive SLE who had no history of thrombosis or thrombocytopenia. Our results underscore the importance of studying unselected patient groups when correlating laboratory data with clinical manifestations of disease. PMID- 3107578 TI - Anticardiolipin antibody. PMID- 3107579 TI - Morphological changes in Neisseria gonorrhoeae induced by various subinhibitory concentrations of cefotiam. AB - A wide variety of morphological changes is induced in gonococci exposed to subinhibitory concentrations of cefotiam. The spectrum reaches from phenomena like enlargement or lysis of cells which can already be seen on the light microscopic level to others which can only be detected by ultrastructural analysis. Most of the changes rarely also occur during the life cycle of gonococci not exposed to an antibiotic. Yet they are more frequent and also more distinct even in the presence of rather low concentrations of cefotiam. The development of mixed (layered and tubular) and even further disorganized mesosomes, however, seems to be characteristic of antibiotic interference. PMID- 3107580 TI - Diphtheria presenting in the accident and emergency department. AB - A case of diphtheria encountered in the accident and emergency department is described. In addition, 38 cases of diphtheria have been analysed, and demonstrate that, although now rare in this country, the disease still exists and its clinical features remain unchanged. It presents almost as often in the accident and emergency department as it does to the general practitioner and remains overwhelmingly a disease of children. Diphtheria is still a notifiable disease. The diagnosis must be made clinically and appropriate action taken before the bacteriological confirmation is received. This prevents unnecessary delay in treatment and makes contact tracing less arduous. PMID- 3107581 TI - Separation of the motivational and motor consequences of 6-hydroxydopamine lesions of the mesolimbic or nigrostriatal system in rats. AB - The effects of 6-hydroxydopamine (6-OHDA) lesions in the ventral tegmental area (VTA) or substantia nigra, pars compacta (SN/pC) on the behaviour of hungry rats were examined in a Columbia obstruction box test. The lesions of dopaminergic neurones in the VTA as well as in the SN/pC decreased the number of crossings of an electric obstruction for food. After the lesion in the VTA the reaction of rats became independent of the level of hunger--the number of their crossings was similar at different levels of hunger. In contrast, no effect of the lesion was found when the animals were trained and tested in the absence of shock. The 6 OHDA lesion in the SN/pC also decreased the number of crossings, but the animals remained sensitive to motivational hunger stimuli: they were still crossing the obstruction in a hunger-dependent manner. Lesions in neither the VTA nor the SN/pC significantly altered the spontaneous food intake and sensitivity to painful electric stimuli. In the Rotarod test only the SN/pC-lesioned rats showed a substantial motor impairment; lesions in the VTA had no effect in that test. The obtained results are discussed in terms of the role of the dopaminergic mesolimbic and nigrostriatal systems in mediation of the motivational arousal and motor performance of an instrumental food response. PMID- 3107582 TI - Impairment of spontaneous alternation behavior in sequential test procedures following mammillary body lesions in mice: evidence for time-dependent interference-related memory deficits. AB - The experiments reported here examined the effects of either radio frequency or kainic acid lesions of the median mammillary nucleus (MM) on spatial spontaneous alternation (SA) in mice. Animals were tested in a T-maze with sessions of six to nine successive trials given at varying intertrial intervals (ITIs). In the first experiment, conducted with an ITI of 30 s, damaged animals exhibited normal rates of SA on the second trial of the session but were progressively impaired on subsequent trials compared with controls. This finding was interpreted as an increased vulnerability to proactive interference. The second experiment was designed to investigate the effect of the ITI, and the results indicated that the previously observed impairment was completely suppressed by reducing the ITI from 30 s to 5 s. In order to further test our interference hypothesis, a third experiment was designed to investigate whether providing the animals with an extrinsic cue on one trial (5th) would increase the rate of SA on the subsequent (6th) trial (release from interference). Unexpectedly, results from this experiment showed that performance dramatically improved as soon as the cue was provided (i.e., on the 5th trial). These results are discussed in relation to a possible role of the mammillary bodies in memory processes. Specifically, it is suggested that as for Korsakoff patients, MM damaged mice suffer from an impaired ability to make temporal order judgments. Thus changing the context serves to help the animal actively reconstruct the sequence of past events. PMID- 3107583 TI - 16th forum in immunology. The role of the CD4 (L3T4) molecule in T-cell activation. PMID- 3107584 TI - L3T4 interacts with class II molecules on target cells. PMID- 3107585 TI - Anti-L3T4 monoclonal antibody inhibits T-cell activation by anti-T-cell receptor antibody through a pathway not involving "associative recognition". PMID- 3107586 TI - The role of L3T4 (CD4) in T-cell activation. PMID- 3107587 TI - Structure and potential function of the murine L3T4 molecule. PMID- 3107588 TI - The role of CD4/L3T4 in T-lymphocyte function. PMID- 3107589 TI - P815 mastocytoma cells, classical targets for cytotoxic T lymphocytes, exert natural cytotoxicity. AB - While investigating the tissue distribution of cytotoxic-T-lymphocyte-associated (CTLA) gene transcripts, we found that some of these could be detected in mast cells. This led us to test the cytolysis exerted by a number of mast cell populations. We briefly report here that P815 cells, classically known as excellent target cells for cytotoxic T cells, exert natural cytotoxicity toward WEHI-164 target cells. PMID- 3107590 TI - Recognition of hybrid HLA molecules expressed on murine P815 cells using human alloreactive cytotoxic T lymphocytes. AB - The HLA-A2 and -A3 genes were used to construct intra-exon hybrids in which part of the third exon (corresponding to the second domain) was of one type and the rest of the other. Murine P815 cells expressing these hybrid constructs were assayed with human alloreactive cytotoxic T-lymphocyte lines specific for either HLA-A2 or HLA-A3. Specific recognition patterns were obtained which indicate that, in some cases, a small portion of the HLA-A2 sequence in an HLA-A3 background is sufficient for recognition by HLA-A2-specific cytotoxic T cells. PMID- 3107591 TI - Monocytes activate eosinophils for enhanced helminthotoxicity and increased generation of leukotriene C4. AB - Recent observations have shown that eosinophils are activated in certain clinical conditions and that activation may enhance the role of eosinophils in immune protection against helminth parasites and in the pathogenesis of certain diseases associated with high eosinophilia. Our laboratory has attempted to identify the immunological mechanisms causing such an activation. The data summarized here show that eosinophils can be activated in vitro with supernatants of resting or stimulated monocytes. The supernatants enhance eosinophil helminthotoxicity by increasing cell degranulation; they also enhance the generation of leukotrienes in eosinophils by exerting a permissive effect on an early step of arachidonic acid metabolism. Biochemical analysis of the enhancing activities suggests that they are carried by a unique molecule or a unique set of molecules whose biochemical and functional properties are different from those of previously described monokines such as IL-1, IFN-alpha,beta, CSF and TNF. Studies on individuals with chronic schistosomiasis suggest that such regulatory interactions between eosinophils and macrophages may take place in the hepatic granulomatous reactions in patients with hepatosplenic schistosomiasis. PMID- 3107592 TI - An eleven year survey (1975-1985) of fulminant hepatitis: considerations on epidemiology and pathogenesis. AB - This review covers 42 patients with fulminant hepatitis treated at the Clinic of Infectious Diseases of University of Pavia over a period of 11 years (1975-1985). This group is 1.9% of the 2181 subjects hospitalized for viral hepatitis, and consists of 25 males (59.5%) and 17 females (40.5%) with a mean age of 44 years. 26 patients (62%) had a virus B hepatitis, whereas in the remaining 16 the non-B type was diagnosed. B hepatitis had an overall prevalence of 56.4%. No case of fulminant hepatitis showed prothrombin levels above 23 (overall average 14%) and bilirubin below 17 mg/dl (overall average 24.5 mg/dl). SGOT and SGPT values were 1684 and 1868 UI/l respectively. 24 patients (57.1%) developed coma after admission to hospital and 18 had this diagnosis upon entry. History evidenced a heroin habit for 6 patients (14.2%); antiblastic treatment for 13 (30.9%); a preexisting liver disease for 7 (16.6%); other major pathologies for 6 (14.2%); steroid anabolizers, barbiturates + pirazolone derivatives and oral contraceptives use for 4 (9.5%) respectively. The overall mortality rate was 90.5%. 17 subjects (40.4%) were treated in an intensive care unit with a mortality rate of 75%. PMID- 3107593 TI - [New findings on the immunology of bronco-82]. AB - The effect of Bronco-82 treatment, a bacterial polyvalent vaccine, was determined on some of the most significant parameters of the immune response, i.e. PHA induced blastogenesis, secretory IgA levels, IL 2 receptor expression, human T cell activation antigen (MLR 3) and gamma-interferon production. The results obtained pointed out a high immunostimulating activity of the vaccine on the parameters considered. Some aspects of the complex immunomodulating effects of Bronco-82 are discussed. PMID- 3107594 TI - Enzyme activities and ultrastructure of intestinal epithelium in the mouse treated with chloramphenicol. AB - Several enzyme activities in the enteric mucous membrane (maltase, lactase, leucineaminopeptidase) were assayed and intestinal epithelium ultrastructure was evaluated in mice treated with chloramphenicol, per os, in different doses (50 mg/Kg and 100 mg/Kg), for 10 days. Of the enzyme activities assayed, only leucineaminopeptidase was found to be significantly lower in treated animals than in controls. Enterocyte ultrastructure and mitochondrial morphometrical parameters were not found to be significantly modified in treated animals. PMID- 3107595 TI - Pharmacologic enhancement of composite graft survival. AB - The use of composite grafts in facial reconstruction has been limited by a history of unpredictable survival beyond a radius of 1 cm. Numerous pharmacologic agents have been employed to improve the survival of random skin flaps but, to our knowledge, have not been studied in composite grafts. Three agents that have demonstrated efficacy in random skin flap survival, intravenous heparin sodium, topical nitroglycerin, and intramuscular methylprednisolone sodium succinate, were investigated for their effect on composite graft survival. Using a rabbit model, full-thickness auricular composite grafts were created, rotated 180 degrees, and reattached. At 21 days, all grafts were assessed for area of survival and postexcisional weight. Animals receiving 30 mg/kg of intramuscular methylprednisolone sodium succinate daily, during the first four postoperative days, demonstrated a significant increase in graft survival compared with controls. Heparin and nitroglycerin produced no change compared with controls. Furthermore, the only grafts to achieve 100% survival were found in the group treated with methylprednisolone. PMID- 3107596 TI - Studies on heterocyclic compounds: indol-2,3-dione derivatives. V. Structure antimicrobial activity of aromatic and heterocyclic azomethines of indol- and substituted indol-2,3-dione. PMID- 3107597 TI - [A case of subtentorial ventricular diverticulum accompanied with choroid plexus papilloma in the lateral ventricle]. AB - Marked non-communicating hydrocephalus may rarely cause ventricular rupture producing either a dilated cystic cavity (ventricular diverticulum) or communication between ventricle system and subarachnoid space (spontaneous ventriculostomy). Ventricular diverticulum has been believed to be collection of cerebrospinal fluid which escaped beneath the pia mater after rupture of ependymal layers and cerebral parenchyma. We proposed herein to report a case of subtentorial ventricular diverticulum which accompanied with choroid plexus papilloma of the lateral ventricle. A nine year-old girl admitted to our hospital complaining of clumsiness of hands and walking, disability of reading, headache and vomiting. The neurological examination revealed alexia, papilledema, anisocoria, righ hemianopsia, weakness of right upper limb, and cerebellar ataxia. CT brain scan showed a large high density area at the trigone of the left lateral ventricle with non-communicating hydrocephalus and an extra-axial low density area in the posterior fossa. The medial space of the left trigone was especially ballooned and is just shifted above incisura tentoria by the tumor. The intraventricular tumor was totally removed by operation and proved to be benign choroid plexus papilloma microscopically. The subtentorial mass was confirmed to be a cyst contiguous to the medial trigone of the lateral ventricle, namely ventricular diverticulum. Three special features were recognized in this case. The first, this was the first example of ventricular rupture accompanied with tumor in the lateral ventricle reviewing all reports of both ventricular diverticulum and spontaneous ventriculostomy. The second, this ventricular diverticulum was not produced merely by hydrocephalus alone but mainly by direct effects of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107598 TI - [Longitudinal study of epileptic foci in childhood]. AB - We performed the longitudinal study in patients with focal spikes about characteristic changes in epileptic foci for periods of between one year and 5 years 9 months. The 116 epileptic children were evaluated, ranging in onset age from 10 month to 12 year 9 month old (mean age: 6 year 11 month). They were subdivided into four groups according to their region of foci: group 1, 41 patients with the centro-temporal spikes (Rolandic discharges); group 2, 14 patients with the occipital spikes; group 3, 6 patients with frontal pole spikes; group 4, 55 patients with the other focal spikes. EEG examinations were followed 6 months interval in each patients, and total 412 EEG trancing were investigated. Migration of epileptic foci was recognized in thirty eight patients (32.8%): 17 (41%) in Rolandic discharges, 7 (50%) in occipital spikes, 4 (67%) in frontal pole spikes and 10 (18%) in other spikes. The mean time to the migration of next foci was 45.6 months in Rolandic discharges, 18.4 months in occipital spikes, 17.6 months in frontal pole spike and 61.4 months in other spikes. As to the regions of migrated foci, Rolandic discharges tended to move to the near and horizontal areas such as from central to temporal. Whereas, occipital spikes and frontal pole spikes tended to move to the distant and vertical areas such as from occipital to frontal pole and from frontal pole to occipital. But other spikes showed no tendency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107599 TI - Carbonic anhydrase isoenzymes in isolated rat peripheral monocytes, tissue macrophages, and osteoclasts. AB - The presence of carbonic anhydrase isoenzymes I and II in rat monocytes and macrophagelike cells was studied using monospecific antisera against rat carbonic anhydrase I and II purified from red blood cells. CA II was strongly stained immunohistochemically in osteoclasts and macrophagelike cells in the umbilical cord. Foreign body giant cells, peritoneal macrophages, lung macrophages, and cultured peripheral monocytes, the presumed progenitor cells for osteoclasts, were negative with both antisera. Radioimmunoassay and immunoblotting similarly failed to demonstrate CA II in peripheral monocytes. The lack of CA in monocytes adds a new aspect to the discussion concerning the origin of osteoclasts and monocyte-mediated bone resorption. PMID- 3107600 TI - Influence of spinal and general anaesthesia on haemostasis during total hip arthroplasty. AB - One hundred and one patients with osteoarthritis were randomly allocated to undergo total hip arthroplasty under either spinal (subarachnoid) or general anaesthesia. Venous blood was sampled before, during and after surgery and on the 5th day after operation to study the haemostatic mechanism. There were no preoperative differences between the two anaesthetic groups. Although there was pronounced individual variability, similar patterns of change in coagulation, platelets and fibrinolysis were seen in both groups. However, there were significant differences between the two groups in platelet count, thrombin production, and Factor VIIIRAg in the intra- and immediate postoperative periods. Also, compared with general anaesthesia, there was less intraoperative activation of fibrinolysis, as measured by the euglobulin clot lysis time, with spinal anaesthesia. These differences suggest slight modification of the haemostatic response to surgery with spinal anaesthesia, which could be consistent with a neuroendocrine mechanism. By the 5th day both groups exhibited a very similar "hypercoagulable" postoperative state. PMID- 3107601 TI - Recovery of bowel motility after surgery. Detection of time of first flatus from carbon dioxide concentration and patient estimate after nalbuphine and placebo. AB - Co-ordinated bowel motility has been studied after surgery. The time to first flatus (TFF) was noted by 20 patients aged 60 yr or older and measured simultaneously using a carbon dioxide analyser. After cystoscopy under general anaesthesia, 10 patients received nalbuphine 20 mg i.v., and 10 patients had placebo (normal saline). In 16 patients (80%) the two observed times coincided and there were no false reports. Two patients were asleep, and did not report TFF. In two others the sampling tube became obstructed. Therefore, both methods are of value; the carbon dioxide analyser, however, is a sensitive and accurate monitor of the initial passage of flatus which does not require patient co operation. In the i.v. nalbuphine group, the median TFF was more than three times as long (212 min) as that in the placebo group (64 min) (P less than 0.01). PMID- 3107602 TI - Effect of pre-treatment with lysine acetyl salicylate on suxamethonium-induced myalgia. AB - The hypothesis that prostaglandin inhibitors might reduce the incidence and severity of suxamethonium-induced myalgia was investigated using lysine acetyl salicylate (LAS) 13 mg kg-1 i.v. 3 min before the administration of suxamethonium in 20 patients. A comparison was made with atracurium 0.09 mg kg-1 (and placebo) in a double-blind prospective randomized trial. LAS and atracurium were effective in reducing the incidence and severity of postsuxamethonium myalgia and the increases in serum potassium concentration. There were no appreciable changes in serum calcium, sodium, chloride, phosphate, magnesium, creatinine, creatine phosphokinase concentrations or plasmacholinesterase activity. Atracurium caused a delay in the onset of action and a decrease in the intensity of suxamethonium induced neuromuscular block. It is concluded that LAS pretreatment might have a place in suitable patients in the prevention of suxamethonium-induced myalgia and increases in serum potassium concentration. PMID- 3107603 TI - Does a bolus of mannitol initially aggravate intracranial hypertension? A study at various PaCO2 tensions in dogs. AB - In two groups of anaesthetized dogs, with (n = 28) or without (n = 28) induced intracranial hypertension, we compared the effects on intracranial pressure (ICP) of the rapid administration of mannitol 2 g kg-1 i.v. at PaCO2 2.7, 4.0, 5.3, and 6.7 kPa (n = 7). In dogs with no induced intracranial hypertension, ICP increased during the administration of mannitol, reached a peak at 2 min after infusion, and then gradually decreased (P less than 0.05). More marked changes in ICP were observed in response to higher values of PaCO2 (P less than 0.05). In dogs with induced intracranial hypertension, the rapid infusion of mannitol caused an exponential decrease in ICP, without initial increase, which was significantly steeper at higher values of PaCO2 (P less than 0.05). This was followed by a more gradual decrease which achieved pre-balloon inflation values 10 min after infusion. We postulate that the absence of the initial increase in ICP is the result of a concomitant decrease in arterial pressure, a reduction in the volume pressure response of the brain, the failure of mannitol to dilate further the cerebral arterial vascular bed and a hitherto unnoticed early water-drawing effect. Our study confirmed the safety of rapidly expanding the circulating blood volume with mannitol in circumstances of increased ICP in dogs. PMID- 3107604 TI - Effect of nitroglycerine-induced hypotension on canine spinal cord blood flow. AB - Twenty-four mongrel dogs were anaesthetized with pentobarbitone and morphine sulphate. Neuromuscular blockade was achieved using pancuronium. Spinal cord blood flow was measured using the radionuclide microsphere and hydrogen washout methods before, during, and following nitroglycerine-induced hypotension. Heart rate, mean arterial pressure, cardiac output, pulmonary capillary wedge pressure, and acid-base balance were determined with each measurement. Mean arterial pressure was reduced by 50%. Spinal cord blood flow, as measured by the microsphere method, increased during the period of hypotension, whereas values obtained using the hydrogen washout method were not significantly different from those at normotension. No significant change in spinal cord blood flow was detected by either method after the application of spinal distraction. Nitroglycerine acts predominantly on venous capacitance vessels and it is postulated that perfusion pressure, and therefore flow, is maintained despite a reduction in arterial pressure. PMID- 3107605 TI - Effects of felodipine on haemodynamics and exercise capacity in patients with angina pectoris. AB - We studied the effects of adding felodipine to beta-adrenoceptor blockade on haemodynamics and exercise capacity in 14 patients with stable angina pectoris using a placebo controlled double-blind crossover protocol. Felodipine reduced supine and standing systolic pressure by 13% (P less than 0.01) and 14% (P less than 0.01) respectively and increased supine heart rate 7.4% (P less than 0.05). Felodipine at a plasma concentration of 15.5 +/- 3.0 nmol l-1 increased exercise duration by 16% (P less than 0.01) but failed to attenuate the degree of ST segment depression during exercise. The mean daily number of episodes of angina (0.53 +/- 0.16 on placebo vs 0.37 +/- 0.11 on felodipine) and mean daily GTN consumption (0.51 +/- 0.07 on placebo vs 0.36 +/- 0.12 on felodipine) were not significantly reduced (0.1 less than P greater than 0.05). These findings suggest that felodipine may provide useful additional benefits in patients with hypertension or angina pectoris, who are already receiving beta-adrenoceptor blockers. PMID- 3107606 TI - Sorbinil pharmacokinetics in male and female elderly volunteers. AB - Sorbinil pharmacokinetics were studied, following a single oral dose, in eight male and eight female healthy, elderly volunteers. Elimination half-life tended to be longer in males than in females. There was no sex difference in AUC or renal clearance. The long elimination half-life of sorbinil in the elderly suggests that accumulation is likely to occur with chronic dosing. PMID- 3107607 TI - Soluble interleukin-2 receptors in the serum of patients with Hodgkin's disease. PMID- 3107608 TI - Phenotypic evolution of CTL B-lines in vitro. AB - This study demonstrates that cytolytic T-cell lines exhibit progressive in-vitro modifications of their phenotype and of their growth behaviour and may use different pathways for their multiplication. Comparing three established cell lines, we firstly demonstrated that the expression of LFA-I is stable but the Lyt 2, 3 is rapidly lost. In this case, a high lectin-dependent cytotoxicity appears. Secondly, we demonstrated that two of the cell lines used the interleukin 2 interleukin 2 receptors (IL-2-IL-2R) binding pathway. Two different monoclonal antibodies showed that the IL-2 receptors distribution does not correlate with the number of functional sites which determines the IL-2 requirement. In contrast, the third cell line, although bearing high levels of IL-2 receptors, grows without the addition of IL-2; this cell growth is not inhibited by anti-IL 2 receptors monoclonal antibodies. Thirdly, it appears that the new property of IL-2 independence is associated with acquisition of the simultaneous capacity to induce tumour grafts in nude mice. As it has been recently reported that cytolytic T-lymphocytes against tumour cells could be promising immunotherapeutic agents, the spontaneous malignant transformation of such CTL lines should be taken into account before using them for adoptive immunotherapeutic purposes. PMID- 3107610 TI - Analysis of leucocyte differentiation antigens in blood and bone marrow from patients with Waldenstrom's macroglobulinaemia. AB - Peripheral blood and bone marrow mononuclear cells from 10 patients with newly diagnosed Waldenstrom's macroglobulinaemia were analysed for the presence of leucocyte differentiation antigens using flow cytometry. Most patients had circulating intracytoplasmic-mu cells that were positive for the B-cell specific antigens B1, B2 and B4 and for the plasma cell antigen PCA-1. When such monoclonal cyto-mu + cells were purified by immune rosette depletion they were shown to express B1 to a much lesser extent than B2, B4 and PCA-1. In bone marrow samples cells with a similar phenotype, but with higher B1 expression were found in all patients. When the serum IgM paraprotein concentrations were compared to surface markers longitudinally from presentation and during the first courses of chemotherapy, a decreased serum IgM level was accompanied by a decrease in B1 cells in peripheral blood. These data demonstrate that WM cells possess a unique phenotype with coexpression of B-cell and plasma cell associated antigens. PMID- 3107609 TI - The effect of age and hair colour on human hairbulb tyrosinase activity. AB - We studied tyrosinase activity from human hairbulbs from 51 subjects, aged 5-72 years. We used anagen hairbulbs and grouped the subjects according to hair colour. We did not observe an age-dependent fall in hairbulb tyrosinase activity. We observed considerable inter-individual variation in activity, with a range of 8-342 pmol DOPA formed/three hairbulbs/30 min. The mean tyrosinase activity from red hairbulbs was significantly higher than the mean for the other hair colours. White hairbulbs did not express tyrosinase activity, and specific antibodies to tyrosinase were used to establish that tyrosinase antigen was absent from white hairbulbs. PMID- 3107611 TI - The effect of naturally occurring Rh antibodies on the survival of serologically incompatible red cells. AB - Investigations on six males with naturally occurring Rh antibodies are described. In two subjects in whom the antibody (one anti-E and one anti-D) could be detected only by a two-stage papain technique, the survival of incompatible red cells was normal. In the remaining four subjects, the antibodies (two anti-E and two anti-D) could be detected by the indirect antiglobulin test and, in these, incompatible red cells were destroyed at an accelerated rate; in two of the subjects, 75-99% of the cells were cleared within 24 h; in the other two, 50% of the cells were cleared within 24 h and the remaining cells were cleared far more slowly. All six antibodies were mainly or wholly IgG; a clear-cut immune response was observed in only one case. PMID- 3107612 TI - Luteal phase after ovarian hyperstimulation. AB - The luteal phase was investigated in 17 women with normal menstrual cycles and tubal infertility who were superovulated with clomiphene (9 cycles), clomiphene plus pulsatile human menopausal gonadotrophin (hMG) (12 cycles) and clomiphene plus pulsatile follicle stimulating hormone (FSH) (11 cycles) during an in-vitro fertilization programme. Follicles were aspirated 34-36 h after the onset of the endogenous LH surge. Urinary total oestrogen levels during the first 6 days of the luteal phase were significantly higher, the duration of the luteal phase was significantly shorter and the luteal levels of urinary pregnanediol were significantly lower in the two combination treatment cycles than in the clomiphene only cycles. When the three treatment groups were combined the mid luteal peak pregnanediol levels and the duration of the luteal phase showed significant negative correlations with plasma or urinary oestrogen levels during the follicular and the luteal phase. It is suggested that the luteal function in cycles superovulated with clomiphene/hMG or clomiphene/FSH is disrupted and this is related to the high amounts of circulating oestrogen. PMID- 3107614 TI - The effect of cellular calcium on Na+/K+ cotransport in human red blood cells. AB - The increase in Ca2+ permeability by addition of ionophore A23187 in the presence of external Ca2+ did not alter the bumetanide-sensitive Na+/K+ effluxes in human red blood cells. An inhibition of this pathway by cellular Ca2+ could be observed only under conditions in which the cellular ATP content was drastically depleted. PMID- 3107615 TI - Benzamide-DNA interactions: deductions from binding, enzyme kinetics and from X ray structural analysis of a 9-ethyladenine-benzamide adduct. AB - The interaction of benzamide with the isolated components of calf thymus poly(ADP ribose) polymerase and with liver nuclei has been investigated. A benzamide agarose affinity gel matrix was prepared by coupling o-aminobenzoic acid with Affi-Gel 10, followed by amidation. The benzamide-agarose matrix bound the DNA that is coenzymic with poly(ADP-ribose) polymerase; the matrix, however, did not bind the purified poly(ADP-ribose) polymerase protein. A highly radioactive derivative of benzamide, the 125I-labelled adduct of o-aminobenzamide and the Bolton-Hunter reagent, was prepared and its binding to liver nuclear DNA, calf thymus DNA and specific coenzymic DNA of poly(ADP-ribose) polymerase was compared. The binding of labelled benzamide to coenzymic DNA was several-fold higher than its binding to unfractionated calf thymus DNA. A DNA-related enzyme inhibitory site of benzamide was demonstrated in a reconstructed poly(ADP-ribose) polymerase system, made up from purified enzyme protein and varying concentrations of a synthetic octadeoxynucleotide that serves as coenzyme. As a model for benzamide binding to DNA, a crystalline complex of 9-ethyladenine and benzamide was prepared and its X-ray crystallographic structure was determined; this indicated a specific hydrogen bond between an amide hydrogen atom and N-3 of adenine. The benzamide also formed a hydrogen bond to another benzamide molecule. The aromatic ring of benzamide does not intercalate between ethyladenine molecules, but lies nearly perpendicular to the planes of stacking ethyladenine molecules in a manner reminiscent of the binding of ethidium bromide to polynucleotides. Thus we have identified DNA as a site of binding of benzamide; this binding is critically dependent on the nature of the DNA and is high for coenzymic DNA that is isolated with the purified enzyme as a tightly associated species. A possible model for such binding has been suggested from the structural analysis of a benzamide-ethyladenine complex. PMID- 3107613 TI - Prostaglandin metabolism and intraocular pressure. AB - The plasma lipid alterations characteristic of essential fatty acid deficiency (EFAD) generally appear one to two weeks after the initiation of fat free parenteral nutritional (PN), and may be associated with a reduction in prostaglandin (PG) formation. In the present study the relationship between exclusion of fat from the diet and changes in intraocular pressure (IOP) and PGE2 plasma levels were studied in 28 patients. The results indicated that three weeks after the omission of dietary fat a significant reduction in IOP levels occurred which persisted throughout the follow-up period of 7 (SD 1.2) weeks. Plasma PGE2 levels were also significantly reduced in patients on fat free PN for three weeks as compared with levels measured while patients were on a fat containing diet. This clinical observation is not yet understood and might be related to changes exerted by fatty acid deficiency. PMID- 3107616 TI - Properties of discoidal complexes of human apolipoprotein A-I with phosphatidylcholines containing various fatty acid chains. AB - In this study we demonstrate that apolipoprotein A-I determined the common size classes of discoidal particles formed with numerous phosphatidylcholines, and with ether analogs of phosphatidylcholines. We show furthermore, that the nature of the lipids dictates the distribution of particles among the different size classes. These experiments were performed with discoidal complexes containing various phospholipids (phosphatidylcholines with saturated and unsaturated fatty acid chains of different lengths and the ether analog of 1-palmitoyl-2 oleoylphosphatidylcholine), cholesterol, and human apolipoprotein A-I, prepared by the sodium cholate dialysis method, and fractionated by Bio-Gel A-5m gel filtration chromatography. The complex preparations were analyzed in terms of their average composition, spectral properties of the apolipoprotein, and the dynamic behavior of the lipid domains. Nondenaturing gradient gel electrophoresis was used to analyze the size classes of particles present in the complex preparations. Starting with reaction mixtures containing around 100:1, phospholipid/apolipoprotein A-I molar ratios, complexes were isolated with molar ratios from 40:1 to 100:1. In most complexes apolipoprotein A-I had high levels of alpha-helical structure (65-77% alpha-helix), and tryptophan residues in a nonpolar environment. The lipid domains of complexes exhibited the dynamic behavior expected of the main phospholipid components. In the average size range from 90 to 100 A diameters, discrete particle classes with 80, 87, 102, 108, or 112 A Stokes diameters were observed for all the complexes containing different phospholipids. These discrete, recurring particle sizes are attributed to distinct apolipoprotein A-I conformations and variable lipid content. PMID- 3107617 TI - Changes in unsaturated fatty acids in serum lipids of hamsters infected with schistosomes (S. mansoni). AB - Measurements have been made of the fatty-acid composition of lipids in normal hamster sera compared with sera of hamsters infected with Schistosoma mansoni. The results show a consistent decrease of linoleic and eicosapentaenoic acids, and an increase in arachidonic acid in the phosphatidylcholine and lysophosphatidylcholine of the infected animals. Arachidonic acid was also increased in cholesterol ester, and docosahexaenoic acid was raised in free fatty acid and in phosphatidylcholine in sera from infected animals. PMID- 3107618 TI - [Allosteric properties of phosphorylase b]. AB - Rabbit skeletal muscle phosphorylase b was separated into two fractions by column chromatography on AMP-Sepharose. The first fraction protein was eluted by glucose 6-phosphate while the second fraction protein was eluted in an AMP concentration gradient. The bulk of the protein eluate was represented by the first fraction protein. Chromatography of phosphorylase b from bovine skeletal muscle under identical conditions also resulted in two fractions, however, with a reverse correlation: the bulk protein of this fraction was eluted by AMP. It was shown that the two phosphorylase b forms eluted by glucose-6-phosphate and AMP differ by their kinetic and physico-chemical properties as well as by the SH-group reactivity. The phosphorylase b forms eluted by the nucleotide were practically uninhibited by glucose-6-phosphate. It can thus be assumed that the equilibrium between the "active" (R) and "inactive" (T) conformations of the protein changes depending on metabolic peculiarities of a given tissue used as a source for enzyme isolation. PMID- 3107620 TI - Serial DST, TRH test, and TRH-like immunoreactivity measurements in major affective disorders. AB - Neuroendocrine functions in depressed patients with major affective disorders were serially investigated by the Dexamethasone Suppression Test (DST), the thyrotropin-releasing hormone (TRH) stimulation test, and the plasma TRH-like immunoreactivity (TRH-LI) measurement. Prior to antidepressant therapy, the sensitivity for nonsuppression to the DST was 36.0%, whereas that for blunted thyroid-stimulating hormone (TSH) response to TRH was 28.0%. Both DST nonsuppression and TSH blunting appeared to be state-related markers for depressed patients. Specifically, a significant increase of maximum TSH response to TRH after 4 weeks of antidepressant therapy was associated with clinical improvement. Plasma TRH-LI in depressed patients was significantly lower than that of healthy controls. It is possible that the lower plasma TRH-LI level is related to the pathophysiology of some depressed patients with major affective disorders. PMID- 3107619 TI - Systemic lithium administration alters rat cerebral cortex phospholipids. AB - Systemic lithium administration is known to alter the metabolism of myo-inositol and choline, both of which are precursors for phospholipid synthesis. We report that systemic administration also induces a number of changes in the relative levels of rat cerebral cortex phospholipids, including phosphatidylinositol, phosphatidylcholine, sphingomyelin, and phosphatidylethanolamine. As phospholipids play an integral role in the maintenance of biological membranes, these changes are functionally quite significant and may have implications for a better understanding of lithium's therapeutic actions. PMID- 3107621 TI - Prolactin response to TRH in Alzheimer's disease. PMID- 3107622 TI - The effect of transferrin and lysozyme on antibacterial activity of amniotic fluid. AB - Amniotic fluid obtained from normal full term gestation inhibited the growth of E. coli, Staph. aureus and B. subtilis, while Ps. aeruginosa, Str. faecalis and Str. agalactiae proliferated readily in amniotic fluid. But when amniotic fluid was heated at 100 degrees C for 5 minutes, its antibacterial activity was completely lost. The levels of transferrin and lysozyme in amniotic fluid at term were determined to be 29.1 +/- 17.6 mg/100 ml (n = 90) and 19.1 +/- 8.3 micrograms/ml (n = 145), respectively. Antibacterial activity against E. coli was restored by adding transferrin into heat-treated amniotic fluid at a concentration of 250 mg/100 ml or higher, but simultaneous addition of transferrin and sufficient concentration of iron to form a transferrin-iron complex resulted in the loss of antibacterial activities. When lysozyme was added to the amniotic fluid, which had lost its antibacterial activity through exposure to heat, the antibacterial effect on B. subtilis was restored. The growth of Staph. aureus in heat-treated amniotic fluid was inhibited by the concomitant addition of lysozyme and aminobenzyl penicillin. PMID- 3107623 TI - Stimulatory and inhibitory effects of progesterone on follicular development in the hypophysectomized follicle-stimulating hormone/luteinizing hormone-treated hamster. AB - Cyclic hamsters hypophysectomized at estrus (Day 1 of the cycle) and injected with 5 micrograms follicle-stimulating hormone (FSH) on Day 1 and 20 micrograms luteinizing hormone (LH) in polyvinylpyrrolidone (PVP) from Days 1-4 ovulated 15.3 ova, in response to 30 IU human chorionic gonadotropin (hCG) administered at 1500 h on Day 4 (Kim and Greenwald, 1984). When 1 mg progesterone (P4) was administered daily from Days 1-4 concurrent with the above regimen, ovulation increased to 38 ova, a clearcut superovulatory response. However, daily injection of 1, 10, or 100 micrograms P4 plus FSH and LH reduced the number of antral follicles present on the afternoon of Day 4 to 3-4 per ovary, compared to 9 per ovary after FSH-LH alone, and the ovulation rate was drastically reduced with most animals being anovulatory. Substituting 1 mg 17 alpha-hydroxyprogesterone or estradiol cyclopentylpropionate for P4 on Days 1-4 did not alter the number of antral follicles on Day 4 from FSH-LH alone, whereas 1 mg androstenedione or 1 mg testosterone cyclopentylpropionate reduced the number of antral follicles to 3 or less. Hence, the stimulatory effects of 1 mg P4 are not attributable to its conversion to other P4 derivatives. After the concurrent injection of 1 mg P4 and FSH-LH, on the afternoon of Day 3, an average of only 1.8 large preantral follicles was present per ovary. By the morning of Day 4, however, the ovary contained 14 large preantral and early antral follicles in addition to 8 large antral follicles. Injection of hCG at this time resulted in the ovulation of 14.5 ova.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107624 TI - The glycosaminoglycan chondroitin-4-sulfate alters progesterone secretion by porcine granulosa cells. AB - Porcine granulosa cells from small (1-2 mm), medium (3-5 mm), and large (6-12 mm) antral follicles were cultured in monolayer for 2 to 3 days with 0 to 3 mg of chondroitin-4-sulfate (C-4-S)/ml in the presence or absence of 0.5 microgram follicle-stimulating hormone (NIH-FSH-S13)/ml. Testosterone (1.4 microgram/ml) was added to some cultures as substrate for estrogen synthesis. Progesterone and estrogen secreted into the media were measured by radioimmunoassay. Concentrations of C-4-S similar to concentrations of chondroitin sulfates (CS) reported for small antral or atretic follicles inhibited both basal and FSH stimulated progesterone secretion. Progesterone secretion was not inhibited by C 4-S when pregnenolone was added to the media. Thus 3 beta-hydroxysteroid dehydrogenase activity was not inhibited by C-4-S. Estrogen secretion was also not inhibited by even the highest concentration of C-4-S tested. Testosterone did not influence C-4-S inhibition of progesterone secretion. Granulosa cells from medium-sized follicles were more sensitive to C-4-S than cells from small follicles. Granulosa cells from large follicles were completely resistant to C-4 S inhibition of progesterone secretion. These observations suggest that C-4-S may play a role in altering gonadotrophin-stimulated and basal progesterone secretion in follicles during differentiation of granulosa cells. PMID- 3107625 TI - F.p.l.c. analysis of the leakage products of proteins crosslinked on Dacron vascular prostheses. AB - The haemocompatibility of vascular, Dacron prostheses was improved by coating with albumin and/or collagen crosslinked with glutaraldehyde (GTA) or carbodiimide (CDI). F.p.l.c. (fast protein liquid chromatography) analysis of the products desorbed from polymeric matrices incubated in physiological conditions for periods extended up to 10 d did not detect the monomers or polymers of collagen and albumin but small amounts of degradation products, the molecular weights of which were less than 45,000, thus minimizing an eventual immunogenic response after implantation. However GTA and CDI matrices required extensive washing to neutralize the cytotoxic effect of GTA and achieve the release of CDI from protein complexes. PMID- 3107627 TI - The activity of the pyruvate dehydrogenase complex in heart muscle in the previously obese mouse model. AB - Obese gold thioglucose injected mice were reduced to lean control weight by food restriction. When pair fed with lean controls these animals then gained weight (were metabolically more efficient). Serum glucose was also elevated in this group (14.5 +/- 0.4 (14) vs 12.1 +/- 0.3 mmol/L, p less than 0.001). If previously obese animals were weight maintained with lean controls (by mild food restriction), serum glucose remained at control levels. The activity of the pyruvate dehydrogenase complex in heart muscle was decreased in both obese and pair fed previously obese, whilst it was similar to that of lean controls in the weight maintained previously obese and in obese mice actually dieted. In all obese and previously obese animals serum insulin was elevated. In hearts from control animals subjected to mild food restriction the pyruvate dehydrogenase complex was activated (11.53 +/- 1.80 (5) vs 3.34 +/- 0.62 (9) U/g dry weight), despite a reduced serum insulin level (42 +/- 2 vs 74 +/- 10 microU/ml, p less than 0.01). These diverse changes in the proportion of the pyruvate dehydrogenase complex in the active form and insulin levels argue for a persistent alteration in the sensitivity of the pyruvate dehydrogenase complex to insulin in obesity, as well as indicating that glucose metabolism in obese animals is altered by both body weight and diet amount. PMID- 3107626 TI - Correlation between inhibitory effect on platelet aggregation and disposition of sulfinpyrazone and its metabolites in rabbits. Part I: Single dose study. AB - Simultaneous evaluation of inhibition of the sodium arachidonate-induced platelet aggregation and drug disposition was studied in rabbits receiving single doses of sulfinpyrazone (SO) and its sulfide metabolite (S). The metabolism of SO was found to be interconversible with that of S. Due to the parallelism of disposition profiles, the observed concentration-related inhibition not only strongly correlated with the much more potent sulfide, but also correlated with the p-OH-sulfide (OH-S) or with a summation of two substances. Exaggeration of inhibition at 24-30 h and rebound effect at 48 h were found after the substances were administered. There may exist a circadian rhythm of platelet aggregation. PMID- 3107628 TI - The development pathology of collagen in humans. PMID- 3107629 TI - Predictive markers of chronic liver disease in hemophilia. AB - In an attempt to predict progressive liver damage in hemophiliac patients by noninvasive means, we conducted a retrospective analysis of clinical and laboratory data from 44 liver biopsies taken from 35 hemophiliac patients. This showed that serum IgG was normal in patients with chronic persistent hepatitis (CPH) but significantly elevated in those with chronic active hepatitis (CAH) or cirrhosis (CIR) (P less than .001). Relationships were less significant between liver histology and IgM (P less than .01), IgA (P less than .05), and globulin (P less than .05). This was unaffected by human immunodeficiency virus (HIV) antibody status in asymptomatic individuals. Although patients with progressive liver disease were also older than those with CPH (P less than .001), the immunoglobulin abnormalities were independent of this. Neither clinical examination nor liver biochemistry at the time of biopsy were of significant diagnostic value. Our results indicate that in the absence of AIDS an elevated IgG level is a reliable indicator of progressive hemophilic liver disease. PMID- 3107630 TI - A test for Fanconi's anemia. AB - A simple and reliable cytogenetic test for Fanconi's anemia (FA) that is based on the hypersensitivity of FA cells to mitomycin C (MC) is described. Equal volumes of whole blood from a patient in whom the diagnosis of FA is suspected and from a normal person of the opposite sex are co-cultured in phytohemagglutinin containing medium in the presence and absence of MC. After five days' co cultivation, 100 quinacrine-stained metaphases from both the MC-containing and the MC-free cultures are examined for the presence of a Y chromosome using fluorescence microscopy. In all bona fide FA patients in whom testing was successful, hypersensitivity to MC was readily demonstrated by the striking deficiency of FA metaphases (0.9% to 14.9%) in the MC-containing co-cultures. In contrast, none of the three patients with Diamond-Blackfan anemia and none of the five with undiagnosed conditions reminiscent of FA exhibited hypersensitivity to MC; cells from them, from parents of FA patients, and from several normal laboratory personnel constituted approximately half of the metaphases (40.4% to 71.2%) of MC-containing co-cultures, as would be expected in the absence of hypersensitivity to MC. PMID- 3107631 TI - The proliferative response of B cell chronic lymphocytic leukemia to interleukin 2: functional characterization of the interleukin 2 membrane receptors. AB - To determine the growth properties of B cell chronic lymphocytic leukemia (B CLL) and to identify possible abnormalities thereof, we examined the in vitro action of interleukin 2 (IL2) in four patients. Using radiolabeled IL2 and monoclonal antibodies reactive with IL2 membrane receptors we show that CLL cells, after their activation in vitro, express IL2 receptors of a high- as well as a low affinity type, exactly as has been reported for normal T and B blasts. In three of the four reported cases, CLL proliferation (measured with 3H-thymidine incorporation) depended on the addition of phytohemagglutinin (PHA) to activate the cells and IL2 (optimal concentration, 10 to 100 U IL2/mL). In contrast, the cells of the fourth case of CLL (CLL-4) proliferated in an autonomous fashion, ie, without a need for PHA and IL2 in culture. Specific blocking of the IL2 binding sites with anti-IL2 receptor monoclonal antibodies almost completely inhibited the proliferation of these cells, which indicated that functional IL2 receptors were required for the autonomous proliferation. The demonstration of low concentrations of IL2 activity in the culture medium conditioned by the cells suggests that endogenous IL2 had been responsible for the spontaneous 3H thymidine uptake by the CLL cells of patient 4. However, we were unable to extract IL2 mRNA from the cells (neither fresh nor after various in vitro incubations) in quantities detectable by Northern blot analysis that would prove that the CLL cells of patient 4 were actively synthesizing IL2 during culture. Thus, individual cases of B CLL are subject to variable growth regulation involving functional IL2 receptors on the cell surface: after activation with PHA the cells respond to exogenous IL2 in a fashion similar to normal B lymphocytes, or the cells are stimulated by endogenous IL2 (or an IL2-like activity) and do not require activation with PHA. PMID- 3107632 TI - Liver transplantation in hemophilia A. AB - Four patients with hemophilia A have undergone liver transplantation in our institution, three successfully. The first was a 21-year-old man with chronic active hepatitis (CAH) in whom the effects of previous abdominal operations prevented the satisfactory technical insertion of the new liver. He died intraoperatively. The second patient was a 15-year-old boy with CAH who began to synthesize factor VIII coagulant activity (F VIII:C) within 18 hours of successful liver transplantation and has continued to do so for almost 2 years (F VIII:C range 0.89 to 3.20 U/mL). The first 2 months of his postoperative course were complicated by infections, but since that time he has done well and has returned to school. The third patient was a 48-year-old man with portal fibrosis and severe ascites. He synthesized F VIII:C (range 0.96 to 1.50 U/mL) within six hours after reestablishment of circulation through the new liver. His postoperative course was complicated by numerous infections, and he died with sepsis and an acquired immunodeficiency-like syndrome 4 months after transplantation. The fourth patient was a 47-year-old mild hemophiliac with CAH who produced adequate factor VIII:C levels following transplantation (range 0.79 to 2.80 U/mL). These patients demonstrate that liver transplantation in hemophiliacs with end-stage liver disease may be lifesaving and results in correction of the F VIII:C deficiency and associated hemorrhagic tendency. PMID- 3107634 TI - A human tumor-specific antigen from lung cancer--a new purification method. PMID- 3107635 TI - Acute toxicity of endosulfan to crab: effect on transport property of haemocyanin. PMID- 3107633 TI - Ultrastructural analysis of human natural killer cell activation. AB - In this study we describe characteristic ultrastructural changes of CD3- large granular lymphocytes (LGL), ie, natural killer (NK) cells, following stimulation with recombinant (r) interleukin 2 (IL 2) or r-gamma interferon (r-gamma IFN) and after interaction with K562 target cells (TC) or Sepharose-bound anti-Fc gamma receptor (FcR) monoclonal antibody (MoAb). When compared to resting cells the cytolytic activity of r-IL 2- and r-gamma IFN-stimulated cells against K562 TC was enhanced. The r-IL 2-stimulated LGL were larger and consistently displayed the shape and cytoskeletal rearrangement characteristic of activated cells. The Golgi apparatus was expanded, and the number of electron-dense granules and vesicles was increased. The ultrastructural changes in r-gamma IFN-stimulated LGL were markedly different from those observed following r-IL 2 activation. Cells did not exhibit changes in size, shape, cytoskeletal organization, or in the structure of the Golgi apparatus. However, r-gamma IFN-stimulated cells exhibited distinctive changes in the structure and content of electron-dense granules with deaggregation of the matrix and parallel tubular arrays (PTAs). Within organelles apparently derived from the electron-dense granules, vesicular and tubular structures were noted that may be the morphological equivalent of cytotoxic factors produced by cytolytic effector cells. These ultrastructural observations indicate that r-IL 2 and r-gamma IFN enhance the lytic ability of NK cells by acting on distinct cell machineries. The cytolytic ability was decreased when LGL were pretreated with K562 TC or immobilized anti-FcR antibody. In both experimental conditions cells displayed ultrastructural features indicating activation as well as loss of cytoplasmic granules and other Golgi-derived organelles. Stimulation of r-gamma IFN- or r-IL 2-activated LGL with K562 TC or Sepharose-bound anti-FcR antibody decreased their cytolytic ability, with cells depleted of granules at the ultrastructural level. Intracytoplasmic fusion of granules and a massive release of the granule content were found in r-IL 2 stimulated cells, reminiscent of the mechanism of basophil degranulation. These observations suggest that multiple activation signals involving distinct surface membrane molecules induce release of cytolytic factors by both resting and activated NK cells. PMID- 3107636 TI - Disposition of low and high environmental concentrations of PCBs in snapping turtle tissues. PMID- 3107638 TI - Elimination of 2,4,5,2',4',5'-hexachlorobiphenyl by the purple sea urchin, Strongylocentrotus purpuratus, following single exposure. PMID- 3107637 TI - Toxic effects of organic solvents on the growth of blue-green algae. PMID- 3107639 TI - Influence of light on chlorophyll, a content of blue-green algae treated with heavy metals. PMID- 3107641 TI - Average daily intake of pesticides and polychlorinated biphenyls in total diet samples in Osaka, Japan. PMID- 3107640 TI - Effect of early postnatal exposure to polychlorinated biphenyls (PCBs) on fertility in male rats. PMID- 3107644 TI - Too sick and old for intensive care. PMID- 3107643 TI - Current state of heart transplantation. AB - Heart transplantation has now been accepted as a proven therapy for terminal heart disease by the medical profession and the Government, and in the USA by insurance companies. Major improvements have been achieved in donor and recipient selection and management, organ preservation, immunosuppressive techniques, and the prophylaxis, diagnosis and treatment of infectious complications. The successful introduction of cyclosporin A to clinical heart transplantation in December 1980 at Stanford University heralded a dramatic expansion in the application of heart transplantation, resulting from improved patient survival, a reduction in serious morbidity, a shorter hospital stay and reduced cost. PMID- 3107642 TI - Relative toxicity of para-substituted phenols: log KOW and pKa-dependent structure-activity relationships. PMID- 3107645 TI - Epidemiology of meningococcal infection. PMID- 3107646 TI - Interferon-gamma: actions and importance. AB - Interferon-gamma is an important immune modulator that activates macrophages and enhances their antigen-presenting ability, boosts cell-mediated immune responses and increases antibody formation. It also enhances host cell-mediated immunity against cancer cells and it can inhibit their growth directly. PMID- 3107647 TI - The consequences of loss followed by recovery of noradrenergic nerve function on muscarinic receptors in the chick expansor secundariorum muscle. AB - The effects of chemical sympathectomy with 6-hydroxydopamine on the response of the expansor secundariorum muscle to noradrenergic nerve stimulation, noradrenaline and acetylcholine have been investigated. Expansor muscles from 60 day old chicks were sensitive to noradrenergic nerve stimulation and exogenous noradrenaline but virtually unresponsive to acetylcholine. Chemical sympathectomy with 6-hydroxydopamine caused loss of function of noradrenergic nerves of the expansor muscle, induced supersensitivity to exogenous noradrenaline and gradually increased the response of the expansor muscle to acetylcholine. As the patency of noradrenergic nerves reappeared there was a decline in the extent of supersensitivity to noradrenaline and the response to acetylcholine gradually declined. The time courses of these changes differed, indicating that the mechanisms responsible for changes in response to noradrenaline and acetycholine are different. PMID- 3107648 TI - The identification of autoantigens, autoantibodies and their idiotypes. PMID- 3107650 TI - Full-length ureteric splintage in the management of bilharzial ureteric strictures. AB - Our experience with full-length ureteric splintage is reviewed with a note on the technique and its outcome. It is safe, effective and simple, easy to teach and easy to learn. It is recommended as the operation of choice in bilharzial ureteropathy. PMID- 3107649 TI - Sodium aurothiomalate toxicity and sulphoxidation capacity in rheumatoid arthritic patients. AB - The association between sulphoxidation capacity and sodium aurothiomalate toxicity was investigated in 65 patients undergoing treatment for rheumatoid arthritis. Of those showing side-effects, 30/37 (81%) were also poor sulphoxidizers compared with only 9/28 (32%) in the group not displaying adverse reactions. A patient with poor sulphoxidation had a nine-fold greater risk of developing toxicity. The prior measurement of sulphoxidation capacity may help to identify those patients most susceptible to the deleterious effects of this drug. PMID- 3107651 TI - Gynaecomastia following cytotoxic therapy for testicular cancer. AB - Sixteen patients in complete remission after chemotherapy or radiotherapy for testicular cancer developed gynaecomastia which appeared 2 to 9 months after the end of therapy and had a mean duration of 4.8 months. These patients had statistically significant higher levels of oestradiol, FSH and oestradiol/testosterone ratio than a control group without gynaecomastia that had received similar treatment. Both groups tended to have testosterone levels in the lower normal range and all patients had normal levels of beta-HCG, prolactin and progesterone. The gynaecomastia in our patients was probably the result of an absolute increase in oestradiol or an increase relative to testosterone. Cytotoxic therapy affects both spermatogenesis and Leydig cell function, with a resultant rise in gonadotrophins which may in turn increase testicular oestrogen secretion. In testicular cancer patients, gynaecomastia may be a sign of tumour activity but it may also be caused by hormonal changes resulting from cytotoxic therapy. It is our experience that the latter treatment-related type is harmless, transient and unrelated to the patient's prognosis. PMID- 3107652 TI - Indicators of depressed fibrinolytic activity in pre-operative prediction of deep venous thrombosis. AB - Euglobulin lysis time (ELT), tissue plasminogen activator (tPA), and the fast acting inhibitor of tPA, were measured pre-operatively in 128 patients who underwent elective major abdominal surgery. Deep venous thrombosis (DVT) was detected by 125I-labelled fibrinogen scan in 37 patients (29 per cent) after operation. Pre-operatively, there was diminished euglobulin lysis activity (332 +/- 197 versus 255 +/- 156 min, mean +/- s.d.; P less than 0.025), and tissue plasminogen activator activity (4.2 +/- 9.9 versus 7.7 +/- 14.3 milliunits/ml, mean +/- s.d.; P = 0.094) in patients who subsequently developed postoperative DVT compared with those who did not. There was no significant difference between the two groups in the level of inhibition of tissue plasminogen activator (160.6 +/- 75.4 per cent versus 152.5 +/- 77.5 per cent, mean +/- s.d.; n = 47). Stepwise logistic discriminant analysis of the data obtained preoperatively showed that tissue plasminogen activator, a more specific measure of fibrinolytic activity, was a weaker predictor of DVT than euglobulin lysis time. The results confirm other observations which indicate that lowered fibrinolytic activity is a risk factor for postoperative DVT. In addition, they suggest that this is not due entirely to low levels of activity of tissue plasminogen activator in plasma. PMID- 3107653 TI - Improved wound healing response in surgical patients receiving intravenous nutrition. AB - The wound healing response was assessed in 90 surgical patients by measuring the accumulation of hydroxypyroline that occurred over a 7 day period, in fine tubes of thin walled GORE-TEX placed in the subcutaneous layers of the arm. In 47 patients presenting for intravenous nutrition, the wound healing response was less (0.34 +/- 0.23 microgram hydroxyproline/cm of tubing) than that of 36 normally nourished patients (0.49 +/- 0.30 microgram/cm; P less than 0.01). However, it was higher when measured after intravenous feeding had commenced (0.88 +/- 0.62 microgram/cm; P less than 0.005). In 29 patients two sequential studies of wound healing were conducted over a 14-day period of intravenous nutrition. The mean accumulation of hydroxyproline during the first week of intravenous nutrition was 0.36 +/- 0.24 microgram/cm and this was increased significantly over the second week of feeding to 0.78 +/- 0.67 microgram/cm; P less than 0.005. The wound healing response that occurred in wounds made after a period of pre-operative nutrition was better than that which occurred when only postoperative nutrition had been given (P less than 0.02). These results show that the wound healing response in surgical patients requiring intravenous nutrition is improved by this treatment. This improvement is seen after only one week of therapy and before there is an obvious change in nutritional status. It also appears that the improved wound healing response is more marked when intravenous nutrition is given before, rather than after the surgical procedure. PMID- 3107654 TI - Drug formularies in hospitals. PMID- 3107655 TI - Analgesia in the neonate. PMID- 3107656 TI - Diet of young children and cardiovascular disease. PMID- 3107658 TI - Type II diabetes of early onset: a distinct clinical and genetic syndrome? AB - The inheritance of non-insulin-dependent (type II) diabetes was studied by a continuous infusion of glucose test in all available first degree relatives of 48 diabetic probands of various ages and with differing severity of disease. In an initial study of 38 type II diabetic subjects and their first degree relatives six islet cell antibody negative patients with early onset disease (aged 25-40 at diagnosis) were found to have a particularly high familial prevalence of diabetes or glucose intolerance. Nine of 10 parents available for study either had type II diabetes or were glucose intolerant. A high prevalence of diabetes or glucose intolerance was also found in their siblings (11/16;69%). In a second study of the families of a further 10 young diabetic probands (presenting age 25-40) whose islet cell antibody state was unknown a similar high prevalence of diabetes or glucose intolerance was found among parents of the five islet cell antibody negative probands (8/9; 89%) but not among parents of the five islet cell antibody positive probands (3/8;38%). Islet cell antibody negative diabetics with early onset type II disease may have inherited a diabetogenic gene or genes from both parents. They commonly need insulin to maintain adequate glycaemic control and may develop severe diabetic complications. Early onset type II diabetes may represent a syndrome in which characteristic pedigrees, clinical severity, and absence of islet autoimmunity make it distinct from either type I diabetes, maturity onset diabetes of the young, or late onset type II diabetes. PMID- 3107659 TI - Arterial disease in chronic leg ulceration: an underestimated hazard? Lothian and Forth Valley leg ulcer study. AB - Six hundred patients with chronic leg ulcers were interviewed and examined for evidence of arterial impairment. There were 827 ulcerated legs. Pedal pulses could not be felt in 94 (11%). A Doppler resting pressure index of 0.9 or less was found in 176 legs (21%). Risk factors for arterial impairment included age, ulceration affecting the foot, and a history of claudication, ischaemic heart disease, or cerebrovascular disease. Roughly half the patients with arterial impairment also showed the clinical features of chronic venous insufficiency. Careful assessment for arterial disease is mandatory before patients with chronic leg ulcers are treated with elastic compression. PMID- 3107657 TI - The unacceptable face of tipping. PMID- 3107661 TI - Irritable bowel syndrome as a cause of chronic pain in women attending a gynaecology clinic. PMID- 3107660 TI - Enprostil and ranitidine in prevention of duodenal ulcer relapse: one year double blind comparative trial. AB - One hundred and forty two patients with duodenal ulcer who after a short term study had relief of pain and healed ulcers proved endoscopically were allocated at random to double blind maintenance treatment with enprostil (a synthetic dehydroprostaglandin E2) 35 micrograms or ranitidine 150 mg at bedtime for up to 12 months. Patients were monitored every third month and examined by endoscopy at three, six, and 12 months, or more often if warranted. The cumulative relapse rates in the enprostil group at three, six, and 12 months were 37% (25/67), 56% (37/66), and 62% (41/66), respectively. The corresponding rates in the ranitidine group were 8% (6/71), 19% (13/69), and 29% (20/69). These differences were highly significant and further enhanced by life table analysis adjusting for withdrawals and by an "intention to treat" analysis in which absence of proof of non recurrence was counted as failure, more patients in the enprostil group having been withdrawn because of adverse events or recorded as non-compliant with the protocol. Enprostil 35 micrograms at bedtime cannot be recommended for preventing relapse of duodenal ulcer. Furthermore, the results challenge the clinical relevance of using so called "cytoprotection" for preventing recurrence. PMID- 3107662 TI - Lower oesophageal contractility as an indicator of brain death in paralysed and mechanically ventilated patients with head injury. PMID- 3107663 TI - Effect of combined implants of oestradiol and testosterone on libido in postmenopausal women. PMID- 3107664 TI - Medical leeches as sources of wound infection. PMID- 3107665 TI - Primary myelodysplastic syndrome and cancer. PMID- 3107666 TI - Chronic lymphocytic leukaemia contemporaneous with HIV infection. PMID- 3107667 TI - Fitness, unfitness, and phosphate. PMID- 3107668 TI - Are general practitioners doing enough to promote healthy lifestyle? Findings of the Medical Research Council's general practice research framework study on lifestyle and health. AB - The health survey questionnaire was used to collect information about cigarette smoking, alcohol consumption, physical exercise, and dieting and weight. Completed questionnaires were received from 25,496 men and 36,657 women registered with 47 group practices in England and Scotland. The proportions of respondents who stated that they had a problem ranged from 1% (women and drinking, n = 406) to 34% (women and weight, n = 12,526). Between 49% (women and drinking, n = 18,048) and 67% (men (n = 17,095) and women (n = 24,550) and weight) thought that their general practitioners should be interested in their lifestyle. The proportions who could recall having received relevant advice ranged from 2% (women and drinking, n = 591) to 24% (women and weight, n = 8946). Advice about smoking had been given to 4055 (40%) of the women and 2941 (39%) of the men who smoked. Only 96 (10%) of the 989 women and 331 (17%) of the 1948 men who drank excessively could recall having received advice about alcohol consumption. These results suggest that patients are concerned about their lifestyle, that most would welcome relevant counselling, and that doctors should become more concerned with prevention of this kind. PMID- 3107669 TI - Can more efficient use be made of x ray examinations in the accident and emergency department? AB - Increasing workloads in our radiology department prompted a study of casualty officers' use of x ray examinations, of which there were 5463 in the period. While casualty officers were in post referrals for x ray examination did not become more selective, but skills in interpreting films improved. Overall, 4.9% of trauma radiographs were misinterpreted, but this fell from 7.1% to 2.9% during tenure of post. One in four errors was clinically important. Clinical guidelines for selective radiography produced a significant and sustained reduction in the number of x ray examinations requested by the department. Analysis of one common injury indicated that the quality of patient care was not adversely affected. The number of x ray examinations carried out in the accident and emergency department can be reduced by using guidelines, and this does not compromise the quality of patient care. Appreciable savings may be made in patients' waiting times and radiodiagnostic expenditure. PMID- 3107670 TI - Irregular vaginal bleeding. PMID- 3107672 TI - Portraits from memory. 11--Lieutenant Colonel Harold J Bensted OBE, RAMC (1888 1966). PMID- 3107671 TI - The aftermath of Angie's overdose: is soap (opera) damaging to your health? AB - In a study designed to evaluate the behavioural impact of a fictional parasuicide -namely, Angie's overdose on the popular television soap opera EastEnders- information about cases of deliberate overdose treated in accident and emergency departments in 63 hospitals throughout Britain was obtained for the week after the televised overdose (experimental period) and the week before the overdose (control period). After adjusting for trends in the equivalent weeks in a control year (1985) the increase in the cases of parasuicide treated by hospitals during the experimental week was not found to be significant. A significant increase (31%) was found among people aged greater than or less than 45, but this is not thought to be reliable. The increase among women alone (21%) was significant with a one tailed test. Contrary to expectations there was a positive association between trends in overdose and distance from London--that is, the further the distance of the region from London the greater the increase in cases of overdose during the experimental period--and a negative association between trends in overdose and viewing figures--that is, the higher the viewing figure the less the impact on the incidence of overdoses. These findings do not lend support to the claim that there was a strong imitation effect after this televised parasuicide. PMID- 3107673 TI - Pretended paralysis requiring artificial ventilation. PMID- 3107675 TI - Impact of cuts in acute beds on services for patients. PMID- 3107674 TI - Environmental factors and disease: the man made environment. PMID- 3107676 TI - AIDS and the heterosexual epidemic. PMID- 3107677 TI - Propofol infusion for sedation in the intensive care unit. PMID- 3107678 TI - Effect of the pollen season on the nasal mast cells. PMID- 3107679 TI - Asthma mortality: comparison between New Zealand and England. PMID- 3107680 TI - An uncompromising report on health visiting for the elderly. PMID- 3107681 TI - Barrett's oesophagus. PMID- 3107682 TI - AIDS and intravenous drug use. PMID- 3107683 TI - Bronchial asthma. PMID- 3107684 TI - Oral acyclovir in acute herpes zoster. PMID- 3107685 TI - Alcohol: an important cause of hypertension. PMID- 3107686 TI - Antenatal, perinatal, or postnatal brain damage? PMID- 3107687 TI - Screening for congenital dislocation of the hip. PMID- 3107688 TI - More evidence on unemployment and health. PMID- 3107689 TI - Treating Paget's disease. PMID- 3107690 TI - Prenatal asphyxia, hyperlacticaemia, hypoglycaemia, and erythroblastosis in growth retarded fetuses. AB - The umbilical venous oxygen and carbon dioxide tensions, pH, lactate and glucose concentrations, nucleated red cell (erythroblast) count, and haemoglobin concentration were measured in 38 cases of intrauterine growth retardation in which fetal blood sampling was performed by cordocentesis. The oxygen tension was below the normal mean for gestational age in 33 cases; in 14 it was below the lower limit of the 95% confidence interval for normal pregnancies. The severity of fetal hypoxia correlated significantly with fetal hypercapnia, acidosis, hyperlacticaemia, hypoglycaemia, and erythroblastosis. These findings indicate that "birth asphyxia" is not necessarily due to the process of birth. PMID- 3107691 TI - Malignant hypertension in women of childbearing age and its relation to the contraceptive pill. AB - Eleven of 34 women aged 15-44 with malignant phase hypertension were taking oral contraceptives at presentation. All had had normal blood pressure before starting to take the pill. In four the interval between the start of oral contraception and the diagnosis of malignant hypertension was less than four months, and in eight no other cause for the hypertension was found. Underlying renal disease and renal failure were less common among pill users than among non-users with malignant hypertension who were of similar age. No pill user became normotensive after withdrawal of the pill, but blood pressure was well controlled (diastolic less than 90 mm Hg) in three patients taking only one drug. By contrast, all 23 non-users needed two or more antihypertensive drugs to control blood pressure. Ten year survival was 90% among pill users and 50% among non-users. These results suggest that oral contraceptives may be a common cause of malignant hypertension in women of child-bearing age. If the pill is stopped and underlying renal disease excluded the long term prognosis for such patients is excellent. PMID- 3107693 TI - Lyme arthritis in southern England. PMID- 3107692 TI - Childhood asthma in adult life: a further study at 28 years of age. AB - A group of 323 subjects who had wheezed in childhood and 48 control subjects of the same age were studied prospectively from 7 to 28 years of age. A classification system based on wheezing frequency was found to correlate well with clinical and spirometric features of airway obstruction. The amount of wheezing in early adolescence seemed to be a guide for severity in later life with 73% of those with few symptoms at 14 continuing to have little or no asthma at 28 years. Similarly 68% of those with frequent wheezing at 14 still suffered from recurrent asthma at 28 years. Most subjects with frequent wheezing at 21 continued to have comparable asthma at 28 years. Of those with infrequent wheezing at 21, 44% had worsened at 28 years. Women fared better than men between 21 and 28 with 19% having worse symptoms compared with 28% of men. Treatment at all ages was generally inadequate. The number of smokers among those with asthma was of concern. PMID- 3107694 TI - Auditory rehabilitation: should we listen to the patient? PMID- 3107696 TI - Haemodynamic changes during the early puerperium. PMID- 3107695 TI - Erythrocyte zinc in differential diagnosis of hyperthyroidism in pregnancy: a preliminary report. PMID- 3107697 TI - Reflections on primary care. Thirst for new wine: responses to "Agenda for discussion". PMID- 3107698 TI - Social class, non-employment, and chronic illness: continuing the inequalities in health debate. AB - The 1981-2 General Household Survey showed steep class gradients in limiting longstanding illness for men and women aged 20-59 that were very similar to the class gradients in mortality in the 1979-83 decennial supplement. The class gradient for women classified by their husband's occupation was stronger than that when they were classified by their own occupation. Men and women who lacked paid employment reported poorer health than the employed and were concentrated in the lower social classes. Inequalities in ill health due to class were partly caused by the higher proportion in the lower social classes who were without work. Class differences in ill health still existed, however, among the currently employed, with unskilled men reporting particularly poor health and women manual workers reporting poorer health than women in non-manual jobs. Class differences were greater for the occupationless than for the currently employed. Thus class remains an important indicator of health inequalities despite the current high level of unemployment. PMID- 3107699 TI - Unemployment and child abuse. AB - The employment state of men living in the homes of children at the time that child abuse was diagnosed was determined. The series included a wide range of abuse, including non-accidental injury, failure to thrive, neglect, and emotional deprivation. Two cohorts of children seen during 1974-9 and 1980-5 were compared; these periods were chosen because a large increase in unemployment began in Sheffield in 1980. Although the proportion of the men without work was significantly increased during the second period, this increase could not be ascribed to the rise in either long term or short term unemployment among those who had previously been in regular employment. It was accounted for by a rise in the proportions of single parent families and families in which the resident man had never had regular employment. This may reflect an increase in pregnancies among young mothers. There was no evidence to support the belief that the loss of a job in otherwise stable families leads to an increase in child abuse. PMID- 3107700 TI - Promoting prevention in primary care: controlled trial of low technology, low cost approach. AB - A study is described in which three general practices were provided with low cost, low technology support from a "facilitator" and were compared with control practices in the ascertainment of major risk factors for cardiovascular disease in middle aged patients. Patients who were attending for a consultation with their general practitioners were recruited to make an appointment with a practice nurse for a health check, and this was compared with ordinary consultations in the control practices. Practices were helped by the facilitator to develop the nurse's role. During the study the increase between intervention and control practices in blood pressure recording was doubled and in the recording of smoking habit it was quadrupled, and there was a fivefold increase in the recording of weight. This model can be applied to other aspects of prevention and general practice care. PMID- 3107701 TI - ABC of AIDS. Development of the epidemic. PMID- 3107702 TI - The natural environment and disease: an evolutionary perspective. PMID- 3107703 TI - Failure to warn. PMID- 3107704 TI - Intensive care: a specialty or a branch of anaesthetics? PMID- 3107705 TI - Long term urethral catheterization in the elderly. PMID- 3107706 TI - LMSSA: a back door entry into medicine? PMID- 3107707 TI - Abdominal aortic aneurysms. PMID- 3107708 TI - Overuse of monitoring of blood concentrations of antiepileptic drugs. PMID- 3107709 TI - Effect of dietary cholesterol on plasma cholesterol concentration. PMID- 3107710 TI - Health care for travellers. PMID- 3107711 TI - Consultant accountability. PMID- 3107712 TI - Aftermath of Chernobyl. PMID- 3107713 TI - Chlormethiazole and alcohol: a lethal cocktail. PMID- 3107714 TI - Congenital rubella in babies of south Asian women in England and Wales. PMID- 3107715 TI - Clinical trials and the acceptance of uncertainty. PMID- 3107716 TI - Kawasaki's disease. PMID- 3107717 TI - The different forms of neurofibromatosis. PMID- 3107718 TI - RAWPing general practice. PMID- 3107719 TI - Look after your heart. PMID- 3107720 TI - Asthma and bronchial reactivity. PMID- 3107722 TI - Mortality from myocardial infarction in different types of hospitals. AB - Hospitals ranging from large urban teaching hospitals to small country hospitals were stratified into four levels of care and examined for their effectiveness of coronary care in relation to these levels. The crude hospital mortality among 2265 patients admitted for definite or possible acute myocardial infarction was 21% at level 1 (the most elaborate level), 22% at level 2, 21% at level 3, and 19% at level 4 (the least elaborate). Adjustment for age or other prognostic factors produced no significant differences across levels either for coronary care unit care or for combined coronary unit and ward care. Success in resuscitation was also similar across levels. These findings suggest that increased resources for coronary care units--whether for new services or for upgrading existing ones--may not be required. PMID- 3107721 TI - Successful treatment of asymptomatic endometriosis: does it benefit infertile women? AB - The relation between asymptomatic endometriosis and infertility was investigated in a randomised double blind placebo controlled trial of the impact of treating the endometriosis with gestrinone. The 12 month cumulative conception rate in those patients treated with gestrinone was 25% (5/20) and in those given placebo 24% (4/17). These same patients were divided into those in whom no visible endometriosis was present at the second laparoscopy and those in whom residual disease was present and the 12 month cumulative conception rates were 25% (4/16) and 30% (6/20) respectively. None of these rates differed significantly, and they compared with a rate of 23% (6/26) in a control group of patients with unexplained infertility. Those patients in whom the disease was eliminated did not return to normal fertility, though all other causes of infertility were excluded. This study failed to show any impact of treatment or the absence or presence of asymptomatic endometriosis on future fertility compared with patients with unexplained infertility. The findings therefore question any causal role of the disease in infertility. PMID- 3107723 TI - Housing conditions and ill health. AB - Lack of empirical evidence that living in damp houses has detrimental effects on health may partly be due to inadequate research. A preliminary study was therefore carried out of a random sample of council owned residences in a deprived area of Edinburgh, a respondent from consenting households being interviewed to obtain a profile of the physical and mental health of all adults and children. In addition, information was gathered about other factors that might be important, particularly smoking and selective bias in the allocation of tenants to houses. Independent measures of dampness were made by environmental health officers. No conclusive effects of damp on the health of adults were identified. Nevertheless, children living in damp houses, especially where fungal mould was present, had higher rates of respiratory symptoms, which were unrelated to smoking in the household, and higher rates of symptoms of infection and stress. Housing should remain an important public health issue, and the effects of damp warrant further investigation. PMID- 3107724 TI - Simple thyroid cyst: cause of acute bilateral recurrent laryngeal nerve palsy. PMID- 3107725 TI - Remission of symptoms in carcinoid syndrome with a new 5-hydroxytryptamine M receptor antagonist. PMID- 3107726 TI - Continuous opportunistic and systematic screening for hypertension with computer help: analysis of non-responders. AB - For two years an office computer was used to identify patients to prompt for opportunistic screening and call for systematic screening. After the two years 92% of patients on the list had had blood pressure readings recorded within the previous five years, of which 34% resulted from special prompts and 22% from screening letters. Those who failed to respond to letters were sent questionnaires, and their records were compared with those of screened patients. With the help of a microcomputer it is practicable to sustain a continuous screening rate of between 90% and 95%. PMID- 3107727 TI - Use of the automatic external defibrillator-pacemaker by ambulance personnel: the Stockport experience. AB - In an attempt to reduce the number of people who die from a cardiac arrest in the Stockport area ambulances were equipped with automatic external defibrillator pacemakers, and ambulance personnel were trained in their use. Over an 18 month period ambulance personnel attended 113 patients in cardiac arrest with these devices. One patient subsequently survived, and three patients survived for up to three days. The reasons for these poor initial results include the failure of bystanders to provide cardiopulmonary resuscitation, a delay in calling for the ambulance, and too few defibrillators being available. PMID- 3107728 TI - Role of macrophages in the pathogenesis of alcohol induced tissue damage. PMID- 3107729 TI - Inner city care. PMID- 3107730 TI - Compulsory detention in hospital under the Mental Health Act 1983. PMID- 3107731 TI - ABC of AIDS. Range and natural history of infection. PMID- 3107732 TI - Spinal cord compression: remember osteoporosis. PMID- 3107733 TI - Consultant accountability. PMID- 3107734 TI - Punctuality. PMID- 3107735 TI - Hypochondriasis: an acceptable diagnosis. PMID- 3107736 TI - Testing the sense of smell. PMID- 3107737 TI - Inadequacy of oleic acids in erythrocytes as a marker for malignancies. PMID- 3107738 TI - Childhood leukemia in relation to nuclear establishments. PMID- 3107739 TI - Torsion of the testis: why is the prognosis so poor. PMID- 3107740 TI - Head injuries in the elderly. PMID- 3107741 TI - Testing for HIV without permission. PMID- 3107742 TI - Bronchial asthma. PMID- 3107744 TI - Pretended paralysis requiring artificial respiration. PMID- 3107743 TI - Case notes chaos. PMID- 3107745 TI - Infection by airborne Chlamydia trachomatis in a dentist cured with rifampicin after failures with tetracycline and doxycycline. PMID- 3107746 TI - Hospital doctor's responsibility for prescribing. PMID- 3107747 TI - Medical staffing and training in the West Midlands region. PMID- 3107748 TI - Bacteriophage therapy. PMID- 3107749 TI - Long-latency spinal reflex in man after flexor reflex afferent stimulation. AB - Electromyographic (EMG) flexor muscle responses evoked by electrical stimulation of ipsilateral peripheral nerves were studied in 16 patients with clinically complete spinal cord transection. Stimuli were applied either to a cutaneous nerve (sural) or to a mixed nerve (tibial) and muscle responses were recorded from tibialis anterior, biceps femoris and rectus femoris. EMG recordings after both sural and tibial nerve stimulation showed that distinct early and late ipsilateral flexor muscle responses could be elicited. This distinction was more evident for tibialis anterior. The latency of the early responses averaged approximately 100 ms with sural and 75 ms with tibial nerve stimulation. This corresponds to the latency of the flexion withdrawal reflex previously described in normal man. After sural stimulation, the early reflex appeared in biceps femoris at a threshold intensity not significantly different from that in normal man given the same stimulation parameters. Late responses appeared after a longer latency (130 ms) and at a lower threshold than the early flexor reflex. In all patients a striking feature of the late response was that its latency increased with increasing stimulus intensity, the maximum latency being as long as 450 ms. This increase also occurred with increasing duration of high intensity stimulus trains. Neither the appearance of a late response nor its latency increase could be explained by a peripheral loop due to a preceding muscle contraction (from either motor axon stimulation or motoneuronal discharge corresponding to the early flexion reflex). It was therefore concluded that both were directly elicited by the afferent volley set up by electrical stimulation. The low threshold of the late reflex corresponded to the excitation of relatively rapidly conducting afferents and its central spinal delay was more than 100 ms. The late reflexes were compared with those described by Anden et al. (1964) in the acute spinal cat injected with DOPA and were found to have similar characteristics. The mechanism for the increase in latency of the late response is discussed in relation to the interpretation of Lundberg (1979). PMID- 3107750 TI - Bradyphrenia in Parkinson's disease and psychomotor retardation in depressive illness. An experimental study. AB - Thirty newly diagnosed patients with Parkinson's disease and 30 patients with primary depressive illness showed slowing of response on a computerized digit symbol substitution test when compared with 30 matched normal control subjects. Significant slowing was related, in the parkinsonian patients, to structural brain disorder and affective impairment and, in the depressed patients, to motor impairment. A second computerized test, cognitively simpler but requiring the same motor response, was also administered to each subject. Both cognitive and motor slowing seemed to contribute to slowing of response in the digit symbol test in both parkinsonian and depressed patients. The tests were repeated after about six months in 12 subjects from each group. The parkinsonian patients, on dopaminergic treatment, showed neither significant change in motor or affective impairment, nor improvement in response time for the digit symbol test, but change in response time was related to change in depression rating. The depressed patients, on conventional treatment, showed significant improvement in both affective and motor impairment and improvement in response time for the digit symbol test, due to improvement in cognitive slowing. It is proposed that bradyphrenia in Parkinson's disease and psychomotor retardation in depressive illness are closely related, and that impairment of dopaminergic systems may be involved in both. PMID- 3107751 TI - Proto-oncogene c-fos is highly induced by disruption of neonatal but not of mature brain tissue. AB - The proto-oncogene c-fos can be induced in cells to high transcript levels by numerous exogenous stimuli. We show here by S1 nuclease protection assay that mere mechanical disaggregation and incubation at 37 degrees C induces high levels of c-fos hnRNA and subsequently of mature mRNA in neonatal mouse cerebellar tissue. This specific increase of c-fos steady-state levels is dependent on the incubation time with a maximal level of induction (over 40-fold) after approximately 1 h. The accumulation of c-fos transcripts is suppressed by alpha amanitin while cycloheximide intensifies induction only moderately. Excessive elevation of c-fos mRNA levels is age-dependent and occurs only in early postnatal but not in adult cerebellar tissue. We conclude that the steady-state level of c-fos transcripts is inducible in a development-dependent manner, and thus may be involved in normal neurogenesis of the mammalian cerebellum. PMID- 3107752 TI - Effects of triethyltin bromide on protein phosphorylation in subcellular fractions from rat and rabbit brain. AB - Phosphorylation of specific proteins in subcellular fractions of rat brain is affected by the presence of low concentrations (1-50 microM) of triethyltin bromide (Et3SnBr), in vitro. SDS-PAGE and autoradiography showed that Et3SnBr increased phosphorylation of an Mr = 42,000 phosphorylation of an Mr = 52,000 component. The Mr = 42,000 and 76,000-80,000 phosphoproteins have been identified as the alpha-subunit of pyruvate dehydrogenase (PDH) and synapsin, respectively. Et3SnBr-induced phosphorylation of rabbit brain PDH results in partial inactivation of the PDH complex. PMID- 3107753 TI - GABA-antagonist inverts movement and object detection in flies. AB - Movement detection is one of the most elementary visual computations performed by vertebrates as well as invertebrates. However, comparatively little is known about the biophysical mechanisms underlying this computation. It has been proposed on both physiological and theoretical grounds that inhibition plays a crucial role in the directional selectivity of elementary movement detectors (EMDs). For the first time, we have studied electrophysiological and behavioral changes induced in flies after application of picrotoxinin, an antagonist of GABA. The results show that inhibitory interactions play an important role in movement detection in flies. Furthermore, our behavioral results suggest that the computation of object position is based primarily on movement detection. PMID- 3107754 TI - Neuronal evidence that inferomedial temporal cortex is more important than hippocampus in certain processes underlying recognition memory. AB - Amnesia has been reported to result from combined damage to the amygdala, hippocampus and inferomedial temporal cortex in man and monkey. Evidence is presented that neuronal activity in the monkey inferomedial temporal cortex reflects memory for the previous occurrence of visual stimuli: 26 (15%) of 173 single units responded more strongly to first than to subsequent presentations of unfamiliar stimuli. No such responses were found for neurones recorded in the hippocampus and subicular cortex. The findings suggest that the inferomedial temporal cortex plays a central role in processes necessary for recognition memory. PMID- 3107755 TI - The central amygdala and immobilization stress-induced gastric pathology in rats: neurotensin and dopamine. AB - Bilateral microinjections of neurotensin (3, 10 and 30 micrograms) into the central amygdala had a dose-related attenuating effect on cold-restraint gastric ulcers in rats. Similar inhibitory effects were also observed with intra amygdalar dopamine (3, 10 and 30 micrograms). Pretreatment with 6-hydroxydopamine (10 micrograms) or haloperidol (1 mg/kg), however, reversed the ulcer attenuating effect of neurotensin. The results indicate that the central amygdala is important in the mediation of the cytoprotective effects of neurotensin and dopamine. PMID- 3107756 TI - Expression of apolipoprotein E by mouse brain astrocytes and its modulation by interferon-gamma. AB - We have found that mouse brain astrocytes in culture synthesize and secrete apolipoprotein E (ApoE) and that its expression is modulated by interferon-gamma, which influences the functional state of astrocytes. Interferon-gamma, which induces expression of Ia determinants on the surface of the astrocyte, reduced secretion of ApoE while enhancing intracellular expression of ApoE. Our data suggest that the synthesis and secretion phases of the ApoE pathway are regulated independently. It is possible that, by the production of ApoE, astrocytes may perform functions that are usually ascribed to macrophages and that may be important in immune reactivity in the brain. PMID- 3107757 TI - Ectopic axon hillock-associated neurite growth is maintained in metabolically reversed swainsonine-induced neuronal storage disease. AB - An experimentally induced and reversible model of a neuronal storage disease, swainsonine-induced feline alpha-mannosidosis, has been used to study the modifiability of ectopic, axon hillock-associated neurites and their new synaptic contacts. Earlier studies have fully documented that a variety of neuronal storage disorders are characterized by such changes in neuronal geometry and connectivity. Swainsonine administration was ended after 6 months of continuous treatment which had resulted in characteristic signs of alpha-mannosidosis. Studies of this animal 6 months after reversal showed that even though neuronal vacuolation and other CNS changes essentially normalized, ectopic neurites and their synaptic connections were still present and appeared similar to those of another animal which had been treated with swainsonine for the entire 12-month period. These results suggest that once initiated during the disease process, ectopic axon hillock-associated dendrites become an integral part of the soma dendritic domain of affected neurons and may not be reversible. These findings may have relevance for current attempts to devise therapies involving enzyme replacement for individuals with inherited neuronal storage disease. PMID- 3107758 TI - Immunohistochemical localization of guanine nucleotide-binding protein in rat retina. AB - The localization of a guanine nucleotide-binding protein, Go, in rat retina has been immunohistochemically examined by use of affinity-purified antibody against the alpha-subunit of Go. Dense Go-immunoreactive products are localized in the inner and outer plexiform layers which are considered as the region of synaptic interplay between neuronal components of the retina. Weak Go-immunoreactivity is also found in the neuropil of the ganglion cell layer and the inner nuclear layer. The selective enrichment of Go in synaptic zones of the retina suggests its major role in neuronal transmission within the retina. PMID- 3107759 TI - Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity. AB - The VTA contains the A10 group of DA containing neurons. These neurons have been grouped into nuclei to be found on the floor of the midbrain tegmentum--Npn, Nif, Npbp and Nln rostralis and caudalis. The VTA is traversed by many blood vessels and nerve fibers. Close to its poorly defined borders are found DA (A8, A9, A11) and 5-HT containing neurons (B8). Efferent projections of the VTA can be divided into 5 subsystems. The mesorhombencephalic projects to other monoaminergic nuclei, the cerebellum and a fine projection descends to other tegmental nuclei as far as the inferior olive. Fibers to the spinal cord have not been demonstrated. The mesodiencephalic path projects to several thalamic and hypothalamic nuclei and possibly the median eminence. Functionally important examples are the anterior hypothalamic-preoptic area, N. medialis dorsalis and reuniens thalami. These two subsystems are largely non-dopaminergic. A minor mesostriatal projection is overshadowed by the large mesolimbic projection to the accumbens, tuberculum olfactorium, septum lateralis and n. interstitialis stria terminalis. There are also mesolimbic connections with several amygdaloid nuclei (especially centralis and basolateralis), the olfactory nuclei and entorhinal cortex. A minor projection to the hippocampus has been detected. The mesocortical pathway projects to sensory (e.g. visual), motor, limbic (e.g. retrosplenial) and polysensory association cortices (e.g. prefrontal). Prefrontal, orbitofrontal (insular) and cingulate cortices receive the most marked innervation from the VTA. A more widespread presence of DA in other cortices of rodents becomes progressively more evident in carnivores and primates. Most but not all projections are unilateral. Some neurons project to more than one area in mesodiencephalic, limbic and cortical systems. The majority of these fibers ascend in the MFB. Most areas receiving a projection from the VTA (DA or non-DA) project back to the VTA. The septohippocampal complex in particular and the limbic system in general provide quantitatively much less feedback than other areas. The role of the VTA as a mediator of dialogue with the frontostriatal and limbic/extrapyramidal system is discussed under the theme of circuit systems. The large convergence of afferents to certain VTA projection areas (prefrontal, entorhinal cortices, lateral septum, central amygdala, habenula and accumbens) is discussed under the theme of convergence systems.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3107760 TI - Nature of salivation produced by thyrotropin-releasing hormone (TRH). AB - In the unanesthetized cat, TRH was injected into the cerebral ventricles (ICV) through chronically implanted cannulae and the nature of the evoked salivation was investigated. TRH injected in doses from 0.1 to 1.0 mg evoked salivation which was not dose-dependent. The antimuscarinic drug atropine as well as the ganglionic blocking agent mecamylamine injected also ICV prevented the salivation induced by ICV TRH. On the other hand, virtually no effect on the TRH-salivation was induced by the following drugs injected ICV: alpha and the beta adrenergic blocking agents, yohimbine and propranolol; dopamine antagonist, chlorpromazine; 5-hydroxytryptamine antagonist, methysergide; and the antihistamine, antazoline. Further, in cats pretreated with ICV reserpine and 6-hydroxydopamine, but not with ICV 5,6-dihydroxytryptamine and hemicholinium, the salivation caused by ICV TRH was abolished. It is concluded that central cholinoceptive and catecholaminergic mechanisms are involved in the salivation induced by ICV TRH. PMID- 3107761 TI - Release and antimicrobial activity of silver sulphadiazine from different creams. AB - The release and antimicrobial activity of silver sulphadiazine from five different creams were studied: unguentum emulsificans aquosum, unguentum hydrophylicum non ionogenicum, paraffin cream (15 per cent), a homemade preparation and a commercially available preparation (Flamazine). A diffusion cell was used to measure the release and the agar well diffusion technique to determine the antibacterial activity of the silver sulphadiazine released. The paraffin cream (15 per cent) preparation had the highest release rate, followed by the homemade cream and the commercially available cream. The antibacterial activity ran parallel with the release results. This study shows the silver sulphadiazine paraffin cream to be superior to the other four preparations, including the commercially available silver sulphadiazine cream, using release and antibacterial activity as criteria. PMID- 3107762 TI - Smoke inhalation injury from newer synthetic building materials--a patient who survived 205 days. AB - A 25-year-old factory worker sustained inhalation injury and 2 per cent deep burns while fighting a fire in his factory (LSI factory) which was made of new synthetic building materials. He became unconscious and inhaled noxious substances from the smoke. Although he survived the acute stages following injury, his pulmonary function subsequently deteriorated with a damaged trachea and bronchi, repeated attacks of pneumonia, atelectasis, pneumothorax and lung fibrosis, leading to death with hypercapnia (PaCO2 more than 100 mmHg) after 205 days in hospital. Autopsy revealed scarring contraction and dilatation of the trachea and bronchi, acquired bronchiectasis, lobular pneumonia, bleeding, hyperaemia and oedema of the lungs. Systemic administration of corticosteroids was only transiently beneficial in reducing the increased airway resistance. PMID- 3107763 TI - Oral hyperalimentation and the prevention of severe weight loss in burned patients. AB - It is well known that the marked hypermetabolic response of the human body to thermal injury requires aggressive nutritional support. In order to minimize catabolic conditions resulting in severe weight loss, an oral hyperalimentation regimen has been successfully implemented in the burns unit of Tygerberg Hospital, Cape Town. Ninety-eight patients with deep burns, varying from 20 per cent to more than 60 per cent of body surface area, were included in this study. The results indicated a general increase in the percentage of patients who gained weight from week to week after week 2 post-burn in all burns categories. An exception was the 60 per cent and more burns category in which an increasing number of patients lost weight until week 4 post-burn. The results of this study and the apparent discrepancy in the above 60 per cent category are presented. PMID- 3107764 TI - [A variety of human autoantibodies recognizes in HeLa cells 2 proteins related to the TFIIIA factor of Xenopus laevis which regularizes the transcription of ribosomal 5S RNA]. AB - Using the sera from two patients with autoimmune disorders, we have identified by immunoprecipitation of HeLa cell extracts two proteins with apparent molecular masses of 37 kDa (p 37) and 32 kDa (p 32). These proteins are associated with 5 S RNA. They are antigenetically related to Xenopus laevis 5 S RNA transcription factor TFIIIA, which is very abundant in early oocytes of this species. In contrast to what is observed in X. laevis oocytes, the TFIIIA-related proteins of HeLa cells are present in very small amounts. Our data suggest that proteins p 37 and p 32 are involved in the control of 5 S RNA transcription. PMID- 3107765 TI - [Implication of HLA class I molecule from monocyte in T-cell activation by CD2 or CD3 monoclonal antibodies]. AB - The role of monocytes in human T-cell activation by monoclonal antibodies (mAb) recognizing CD3 molecule or by 2 mAb pairs directed against different epitopes of CD2 "GT2+T11(1)" or "D66+T11(1)" has been studied. It appears that HLA-cl I molecules from monocytes are involved in the early activation phase of T-cells stimulated by CD3 or CD2 when direct contacts between T-cells and monocytes are required. Thus, pretreatment of monocytes with HLA-cl I mAb inhibited IL 2 receptor appearance and IL 2 synthesis on T-cells stimulated by CD3 mAb or CD2 "GT2+T11(1)" mAb pair. PMID- 3107766 TI - Imaging in breast cancer. PMID- 3107767 TI - Imaging strategies for tumors of the kidney, adrenal gland, and retroperitoneum. PMID- 3107768 TI - Imaging strategies for tumors of the gastrointestinal system. PMID- 3107770 TI - Regional variations in histomorphometric bone dynamics from the skeleton of an osteoporotic woman. AB - Histomorphometric evaluation of bone formation in an intravital tetracycline labeled skeleton of a suddenly deceased osteoporotic woman is presented. The 24 skeletal sites investigated displayed substantial regional variations which, for two out of four cortical bone dynamics and all trabecular bone dynamics, were significantly higher than the intraspecimen variation. Poor agreement was found between bone formation in left- and right-sided iliac crest specimens. Furthermore, no agreement was found between trabecular bone formation and amount of hematopoietic bone marrow. With all the limitations that the study of a single patient involves it is suggested that bone biopsy in individual patients should not be the only basis for therapeutic decisions in postmenopausal osteoporosis; amount of hematopoietic marrow does not seem to influence bone formation; and bone formation in the skeleton displays large regional variations, which are larger for the fraction of labeled surfaces than for appositional rate. PMID- 3107769 TI - The circadian rhythm of serum osteocalcin concentrations: effects of 1,25 dihydroxyvitamin D administration. AB - The effects of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) administration on serum osteocalcin (Oc) concentrations were determined. 2.0 micrograms doses of 1,25(OH)2D3 were administered orally and intravenously to four healthy adult males. Blood was sampled hourly for 24 hours on four occasions: once prior to the two treatment days (i.v. and p.o.), on each of the treatment days, and during a second nontreatment day 2 years later. Mean circadian Oc rhythms of the four subjects on each study day were compared with each other and with a previously derived mathematical representation of the normative Oc rhythm, the circadian Oc rhythm model. We found overall conservation of the mean Oc pattern across time and 1,25(OH)2D3 treatment. However, 1,25(OH)2D3 administration resulted in a rapid rise (within 6 hours) in Oc concentrations that blunted or eliminated the morning fall in Oc levels. The increased Oc levels were sustained for the remainder of the 24 hour period though pattern shapes converged with those of the nontreatment days and the model. We conclude that serum Oc levels are rapidly responsive to near physiological doses of 1,25(OH)2D3 in healthy adult males and that the effects are maintained for at least 24 hours. PMID- 3107771 TI - Effects of neonatal estrogenization on rat bone development: a histomorphometric study. AB - The effects of a single dose of 500 micrograms of estradiol benzoate, administered on the first day of life, on rat bone development have been histomorphometrically studied at 15 days of age. Estrogenized animals presented decreased total tibial length (16.55 +/- 0.50 vs. 17.84 +/- 0.73 mm, P less than 0.05) and increased thickness of the cartilage growth plate (528.92 +/- 13.30 vs. 382.77 +/- 37.85 micron, P less than 0.01). This increase was mostly due to the presence of a wider (P less than 0.01) layer of hypertrophic cartilage in the estrogenized rats than in control ones. It might be related to the decreased number of chondroclasts (0.20 +/- 0.01 vs. 0.36 +/- 0.06 mm-1, P less than 0.05) found in the resorption zone. Two metaphyseal zones have been considered. In the upper metaphyseal zone there was an increase in the surface density of the cartilaginous trabeculae (49.20 +/- 1.80 vs. 40.72 +/- 1.95 mm2/mm3, P less than 0.05), without changes in the volume density. It was related to the presence of thinner and more irregular trabeculae in the estrogenized animals. In the lower metaphyseal zone both the volume (0.19 +/- 0.01 vs. 0.14 +/- 0.01 mm3/mm3, P less than 0.01) and surface (34.83 +/- 3.01 vs. 26.52 +/- 2.46 mm2/mm3, P less than 0.05) densities of the osseous trabecular tissue were increased in estrogenized rats. No significant differences were found either in the number of osteocytes per area unit of osseous tissue or in the number of osteoclasts per unit length of trabecular osseous tissue. PMID- 3107772 TI - Ovariectomy and trabecular bone remodeling in the dog. AB - The early effects of ovariectomy (OX) on serum biochemistry and trabecular bone remodeling in the dog were investigated. Adult beagle dams were ovariectomized (n = 8) or sham-ovariectomized (n = 6) and followed for 6 months. All dogs received an iliac crest biopsy at the time of surgery to establish baseline remodeling data. A second contralateral biopsy was obtained at sacrifice. Serum osteocalcin became significantly elevated approximately 8 weeks following OX and remained elevated for the duration of the study. Histomorphometric analysis of serial transilial specimens showed that, at 6 months, OX had significantly increased the rate of bone remodeling in the ilium. Six months following OX in the dog, changes in serum biochemistry and trabecular bone remodeling in the ilium are consistent with those seen in postmenopausal women suffering from "high remodeling osteoporosis". PMID- 3107773 TI - Indomethacin does not inhibit the anabolic effect of parathyroid hormone on the long bones of rats. AB - Chronic administration of parathyroid hormone, hPTH 1-34, increased bone mass in normocalcemic, young rats. Since PTH can stimulate prostaglandin E2 (PGE2) production in bone in vitro, and since PGE2 can stimulate bone formation, the anabolic effect of PTH could be mediated by PGE2. To test this hypothesis, experiments were done to determine if indomethacin, which blocks endogenous PG production, would inhibit the anabolic response of bone to PTH. In the first experiment, male Sprague-Dawley rats, 70-100 g, in groups of five, were treated for 12 days with either hPTH 1-34, 8 micrograms/100g/day; PTH vehicle; indomethacin, 2 mg/kg/day; or a combination of PTH and indomethacin. In the second experiment, groups of 6 rats each were given vehicle or hPTH 1-34, 8 micrograms/100g/day, in combination with indomethacin, 0, 1, 2, or 4 mg/kg/day. Subcutaneous injections of PTH wee given once daily and indomethacin was given orally in divided doses, twice a day. Rats were killed on day 12 in both experiments; their sera were analyzed and the trabecular and cortical bone of distal femurs processed to determine calcium (Ca) and hydroxyproline content and dry weight. PTH and indomethacin had no significant effect on serum Ca, phosphate, alkaline phosphatase, urea nitrogen and creatinine, or systemic and long-bone linear growth. In rats treated with PTH alone or in combination with indomethacin, bone Ca of distal femurs increased by 28-44%; dry weight by 29-41%, and hydroxyproline by 17-45%. Indomethacin alone had no effect on bone growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107774 TI - Electron microscopic study of chondroid tissue in the cat mandible. AB - This paper deals with electron microscopic appearance of chondroid tissue. Samples from eight cat mandibles were studied without decalcification. The ultrastructural characteristics of the chondroid tissue cells are common with young osteocytes. The interterritorial matrix of chondroid tissue is mineralized, being constituted of large collagen fibrils and calcospherites. The compositions of these parts of the chondroid tissue matrix and of bony matrix are similar but they are two different tissues. The pericellular matrix of the chondroid tissue consists of finely branched filaments, thin collagen fibrils, and an abundant ground substance. It resembles a cartilage matrix and contains type II collagen which is not present in bony matrix. PMID- 3107775 TI - Effect of cortisol on [3H] 1,25-dihydroxyvitamin D3 uptake and 1,25 dihydroxyvitamin D3-induced DNA-dependent RNA polymerase activity in chick intestinal cells. AB - The influence of cortisol on intestinal DNA-dependent RNA polymerase activity was studied in purified nuclei of vitamin D-deficient or 1,25-dihydroxyvitamin D3 treated chicks. Six- to 7-week-old vitamin D-deficient cockerels were given 5 mg of cortisol or vehicle intraperitoneally 24 and 48 hours before sacrifice. Three hours before sacrifice, 200 ng of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was administered intracardially. Cortisol did not alter the uptake or metabolism of 1,25(OH)2D3 in the intestinal mucosa. After a 200 ng dose of 1,25(OH)2D3 the in situ intestinal ligated loop technique revealed a 39% increase in calcium absorption compared to control birds (P less than 0.001). The administration of cortisol (5 mg) to chickens given 1,25(OH)2D3, however, resulted in a significant decrease in intestinal calcium transport in vivo (P less than 0.0025). When intestinal nuclei were prepared from birds treated in a manner identical with that described above, 1,25(OH)2D3-treated and 1,25(OH)2D3 plus cortisol-treated chicks had intestinal RNA polymerase II transcriptional activities that were significantly greater than those of vitamin D-deficient controls (P less than or equal to 0.02, P less than or equal to 0.005). There was no difference between RNA polymerase II and I + III activities of the 1,25(OH)2D3-treated birds and that of the cortisol plus 1,25(OH)2D3-treated birds. Vitamin D-deficient chicks treated with cortisol alone showed RNA polymerase I + III activity that was significantly higher (P less than or equal to 0.01) than that of birds treated with vehicle alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107776 TI - Effect of aging on vitamin D stores and bone density in women. AB - It has been suggested that the decrease in vitamin D stores with aging is a contributory cause of age-related osteoporosis. We studied this question by measuring bone mineral density (BMD) of the mid-radius, distal radius, and lumbar spine assessed by single and dual photon absorptiometry in 122 women, aged 33-94 years, selected from a random sample of Rochester, MN residents. We measured serum 25-hydroxyvitamin D (25OHD), the major storage form of vitamin D, as well as 25OHD3 (representing both endogenous and exogenous sources of vitamin D), and 25OHD2 (representing only exogenous sources). Both baseline serum total 25OHD (r = -0.29, P less than 0.001) and the metabolite 25OHD3 (r = -0.41, P less than 0.001), were negatively associated with age at baseline. After adjusting for the effect of age by multiple regression analysis, there was no association between serum levels of 25OHD2, 25OHD3, or total 25OHD and BMD for any of the three skeletal scanning sites. Thus, in a northern American population we cannot demonstrate that reduced bioavailability of vitamin D plays a major role in age related bone loss. PMID- 3107777 TI - Infantile hypophosphatasia: enzymatic defect explored with alkaline phosphatase deficient skin fibroblasts in culture. AB - Evidence that infantile hypophosphatasia may result from defective regulation of an intact structural gene for the tissue nonspecific (bone/liver/kidney) isoenzyme of alkaline phosphatase (TNSALP) was explored by studying physicochemical properties of ALP in sonicates of monolayers of cultured dermal fibroblasts from 7 patients (PT) and 5 age- and sex-matched control (CT) subjects. Both groups had low levels of ALP activity when assayed with 4 methylumbelliferyl phosphate substrate. The mean specific activity of ALP in the PT fibroblasts was markedly subnormal (Vmax less than 1% of CT), but apparently not from extracellular loss of enzyme, since defined medium had less ALP activity when conditioned by PT compared to CT cells. Although the mean Km for the sonicate ALP was similar for both groups at pH 10.1, pH optimum, thermal stability and response to several inhibitors appeared to be different. Nevertheless, it seemed that some TNSALP-like enzyme was present in the PT group. Exposure of cells in culture to 5-azacytidine and several putative inducers of ALP failed to increase the enzyme activity in either the PT or CT groups. Had the physicochemical properties of the constitutive (or inducible) ALP been the same in the PT and CT cell groups, the findings would have provided evidence for the generality of our previous observations in one patient which indicated that defective regulation of an intact structural gene for TNSALP could account for hypophosphatasia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107778 TI - Osteonectin content in human osteogenesis imperfecta bone shows a range similar to that of two bovine models of OI. AB - Samples of human osteogenesis imperfecta (OI) bone were analyzed for osteonectin content by SDS gel electrophoresis and immunodetection on Western blots. The OI bone osteonectin content varied from normal to severely depressed. Previously, we showed that two clinically identical but genetically unrelated bovine models of OI were differentiated biochemically by their bone osteonectin content: one OI model had normal bone osteonectin while the other was severely depressed in this parameter. The data in this pilot study suggest that further investigation of bone osteonectin content may prove useful in the clinical assessment of human OI cases. PMID- 3107779 TI - Binding of calcium by proteoglycans in vitro. AB - Proteoglycans from bovine nasal septa or the Swarm rat chondrosarcoma, as potassium salts, effectively inhibit the precipitation of tricalcium phosphate in vitro at pH 7.8. The same preparations, and many other similar preparations, however, do not site bind calcium, as assessed with a calcium ion specific electrode. However, after treatment of aggregate preparations of proteoglycans with EDTA, the preparations can site bind calcium. The amount thus bound is approximately equal to one-half the sum of the equivalents of the ester sulfate and the uronic acid carboxyl groups in the preparations. This latter observation suggested the possibility that the supposed potassium salts of the proteoglycans had, in the course of preparation, acquired calcium and held onto it strongly. In checking this possibility, using neutron activation analysis, it was found that some of the preparations do contain small amounts of calcium but these amounts are insufficient to saturate the binding sites potentially available to this end. In view of the above observations, it is suggested that the proteoglycans inhibit the formation of calcium phosphate precipitates in vitro not because the calcium is site bound but because the calcium ions are territorially bound. PMID- 3107781 TI - Effects of forskolin on bone resorption in the absence and presence of parathyroid hormone and calcitonin. AB - Release of previously incorporated 45Ca from fetal rat long bones was determined with the diterpene forskolin, both in the absence and presence of parathyroid hormone (PTH) and calcitonin (CT). In the absence of hormone, increased bone resorption was observed with 10(-7)M forskolin, but biphasic responses, consisting of initial decreases in 45Ca release that were followed by increased calcium mobilization, were produced with 10(-6)M and 10(-5)M forskolin. Inhibition of 45Ca release was pronounced and delayed more with 10(-5)M forskolin while the greatest stimulation of bone resorption was elicited by 10(-6)M forskolin, a response that was inhibited by 100 mU/ml CT. In the presence of 250 ng/ml PTH, a synergistic enhancement of 45Ca release occurred with 10(-7)M forskolin treatment while, in contrast, calcium mobilization was inhibited by 10( 6)M and 10(-5)M forskolin. Inhibition by 10(-6)M forskolin was characterized by "escape" while that of 10(-5)M forskolin was continuous over a 5 day interval. Inhibition throughout the experimental period also was noted when 10(-5)M forskolin was combined with 2.5 ng/ml PTH, but no effect on calcium mobilization was observed upon addition of 10(-7)M forskolin and, rather than inhibition, an enhancement of 45Ca release occurred when 10(-6)M forskolin was combined with 2.5 ng/ml PTH. Inhibition of 250 ng/ml PTH, but lack of inhibition of 2.5 ng/ml PTH by 10(-6)M forskolin suggests a 10(-6)M forskolin-sensitive portion of PTH mediated calcium efflux. Absence of "escape" when 10(-5) M forskolin is combined with 250 ng/ml PTH suggests that heterologous desensitization may not play a major role in the "escape" which occurs with 10(-6) M forskolin. PMID- 3107780 TI - Bone modeling in gallium nitrate-treated rats. AB - Gallium nitrate (GaN) reduces cancer-related hypercalcemia and inhibits bone resorption in vitro. This study investigated the effects of chronic GaN administration on bone, kidney, and parathyroid gland activity of growing rats. Experimental animals received GaN (1.75 mg elemental gallium i.p. QOD X 8, Ga+), and controls received the solvent (Ga-). In the bone of Ga+ rats the number of osteoclasts was increased (Ga+: 70.4 +/- 2.31 osteoclasts/mm2; Ga-: 46.5 +/- 1.61 osteoclasts/mm2, P less than 0.001), and apposition rate and osteoid width were unchanged. Ga was concentrated in bone (2.4 mumol/g cortical bone) and detected by electron microprobe on the surface of a few trabeculae. Alkaline (Alp) and acid (Acp) phosphatase activities were higher in Ga+ than in Ga- calvaria (Ga+: Alp 223 +/- 23.4 U/mg prot, Ga-: Alp 145 +/- 13.3 U/mg prot, P less than 0.02; Ga+: Acp 69.5 +/- 4.7 U/mg prot, Ga-: 57.5 +/- 2.8 U/mg prot, P less than 0.05). Serum iPTH was increased (Ga+: 112.9 +/- 17.6 pg/ml, Ga-: 41.4 +/- 7.4 pg/ml, P less than 0.01), serum calcium was reduced (Ga+: 2.4 +/- 0.02 mmol/l, Ga-: 2.6 +/ 0.03 mmol/l, P less than 0.001); calciuria remained comparable to controls. Relative to the hypocalcemia this suggests renal loss of Ca. The calcemic response to hPTH 1-34 (i.v. 50 micrograms/kg) was decreased 2 hours after injection of the hormone (delta Ca: TPTX Ga+: 0.11 +/- 0.04 mmol/l, Ga-: 0.33 +/- 0.03 mmol/l P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107782 TI - Two bovine models of osteogenesis imperfecta exhibit decreased apatite crystal size. AB - In recent years advances have been made in detailing the changes in both collagen and noncollagenous proteins caused by a variety of mutations leading to osteogenesis imperfecta. Much less, however, is known about the mineral phase in the affected bone. In this report, we measured the crystallinity of the apatite in bovine OI bone. Line broadening of the 002 reflection (which estimates changes in the long or c axis of the crystals) and of the 310 reflection (which estimates changes in the thickness of the crystals) both show large decreases (30 and 35% respectively). Transmission electron micrograph measurements indicate that these changes were most probably a result of smaller crystals. No decrease in the ash weight of the bone was observed. PMID- 3107784 TI - Conditioned medium from osteoblast-like cells mediate parathyroid hormone induced bone resorption. PMID- 3107783 TI - Calmodulin in rat incisor secretory ameloblasts as revealed by protein A-gold immunocytochemistry. AB - Thin sections of aldehyde-fixed, undecalcified, embedded rat incisor enamel organ were incubated with sheep antiserum to bovine testes calmodulin to reveal the sites of antigen-antibody reaction at the ultrastructural level in secretory ameloblasts using the protein A-gold immunocytochemical technique. Specific immunolabelling was localized intensely on free polyribosomes and those attached to rough-surfaced endoplasmic reticulum but only rarely observed in the cisternal space. The nuclei, mitochondria, cytosol, and plasma membranes were also immunoreactive. The Golgi membranes and related vesicles, secretion granules, and lysosomes were unlabelled. The proximal and distal cell web junctional complex systems were not immunoreactive. These findings suggest that calmodulin location reflects its synthetic site and multifunctional roles in the immunolabelled cytoplasmic components of secretory ameloblasts. PMID- 3107785 TI - Competition between fatty acids and carbohydrate or ketone bodies as metabolic fuels for the isolated perfused heart. AB - The ability of carbohydrate fuels (lactate, pyruvate, glucose) and the ketone bodies (acetoacetate, beta-hydroxybutyrate) to compete with fatty acids as fuels of respiration in the isolated Langendorf-perfused heart was studied. Oleate and octanoate were used as fatty acid fuels since oleate requires carnitine for entry into mitochondria, whereas octanoate does not. The two ketone bodies inhibited the oxidation of both oleate and octanoate implying an intramitochondrial site of action. Pyruvate, lactate, and lactate plus glucose inhibited oleate oxidation but not octanoate oxidation, indicating a mechanism of inhibition that involves the carnitine system. Pyruvate was a more potent inhibitor than lactate at equal concentrations, but the effect of lactate could be greatly increased by dichloroacetate, an inhibitor of pyruvate dehydrogenase kinase. The physiological and mechanistic implications of these observations are discussed. PMID- 3107786 TI - Mitomycin C pharmacokinetics in patients with recurrent or metastatic colorectal carcinoma. AB - The pharmacokinetics of mitomycin C as a single agent have been determined in 25 treatment courses given to 18 patients with recurrent or metastatic colorectal carcinoma using a high performance liquid chromatography (HPLC) assay to analyze plasma and urine samples. The plasma pharmacokinetics conformed to a two compartment linear model in 21 of 25 courses monitored with a mean t1/2 lambda 1 of 9.8 +/- 1.2 (SEM) min and mean t1/2 lambda z of 64.1 +/- 8.9 (SEM) min. The large variation observed in t1/2 lambda z was not related to dose or treatment, but an interaction of these two factors approached significance (p = 0.057). Renal excretion in the 12 courses in which it was determined averaged only 2.3% of the total administered dose during the first 4 h monitored and no mitomycin C metabolites were detected in plasma or urine by the HPLC technique used. The most common toxicity, thrombocytopenia, did not correlate with t1/2 lambda z or the area under the curve. This may be due to a failure to monitor active metabolites of mitomycin C; other factors besides plasma drug concentrations that mediate toxicity towards marrow elements; or the small number of courses associated with thrombocytopenia (less than 100,000/mm3). Our study indicates that an interaction of drug dose and treatment course may be associated with increasing t1/2 lambda z; the renal clearance contributes a small component of mitomycin C elimination; metabolites of mitomycin C cannot be detected by the present HPLC technique; and routine monitoring of mitomycin C using present methods cannot be recommended for clinical use to predict toxicity. PMID- 3107787 TI - The interaction of histamine with other bronchoconstrictor mediators. AB - The lack of therapeutic efficacy of antihistaminic drugs in the treatment of asthma has led to the search and discovery of other bronchoconstrictor agents, particularly leukotrienes, thromboxanes, and platelet-activating factor. However, specific receptor antagonist for any of these substances have also not been particularly effective in inhibiting allergic bronchoconstriction. It is now generally accepted that histamine, arachidonic acid metabolites, platelet activating factor, and possibly other substances are all involved to varying degrees in asthma and may indeed interact. This paper reviews the interaction of these mediators and how they contribute to airway hyperreactivity. PMID- 3107788 TI - Production of cytotoxin by clinical strains of Pseudomonas aeruginosa. AB - Presence of cytotoxin was studied in extracts of 57 strains of Pseudomonas aeruginosa (46 bacteremia, 4 environmental, and 7 Fisher immunotype), 10 Pseudomonas species, and 7 nonpseudomonas isolates. Cytotoxin was identified by Western immunoblot in extracts of all P. aeruginosa isolates. None of the Pseudomonas species or nonpseudomonas isolates were shown to produce this protein. No immunologic cross-reactivity was observed between cytotoxin antibody and P. aeruginosa alkaline protease, toxin A, or elastase. In partially purified extracts of two bacteremia strains and PA 158 (parent strain for cytotoxin production), detection of cytotoxin by Western immunoblot was correlated with biological activity, as measured by the cell swelling assay. Cytotoxin appears to be produced by all strains of P. aeruginosa and biological activity can be demonstrated in extracts of the strains tested. This biological activity is neutralized by specific antibody. Because of its known marked cytotoxic effect on most eukaryotic cells, P. aeruginosa cytotoxin might be an important factor in the pathogenesis of P. aeruginosa infections. PMID- 3107789 TI - Expenditures on health care in British Columbia. PMID- 3107790 TI - Mycoplasma pneumoniae infections in a rural setting in Canada. AB - Mycoplasma pneumoniae infection was monitored in patients with symptoms of acute respiratory tract infection in a village in southeastern Ontario from April 1983 to April 1984. M. pneumoniae was isolated from 51 (48%) of the 106 patients. The incidence began to increase in May 1983, reached a peak in July and declined to normal by mid-August. During the epidemic period M. pneumoniae was detected in 36 of the 43 symptomatic patients. The most prominent features of the outbreak were the considerable intrafamilial attack rate and the high frequency of pneumonia among infected patients. Treatment with tetracyclines and erythromycin reduced the duration of the illness and accelerated the resolution of symptoms. PMID- 3107791 TI - Canadian surgeon happy to be coming home after stint in US. Interview by Patrick Sullivan. PMID- 3107792 TI - Nutrition services in the continuum of health care. AB - Nutrition services are important components of all phases of the continuum of health care services to older persons. Nutrition and food services can play a major role in improving the health status of older individuals, maintaining their independence and dignity, reducing the rate and length of institutionalization, and possibly lowering health care costs. Nutrition screening and assessment are beneficial to consider when the individual enters the health care system. Monitoring nutritional status periodically helps define the change in the individual's needs over time and provides direction to nutritional care. Nutrition interventions, including clinical nutrition care, counseling, education, and food programs, are important options to consider in attempting to alleviate nutritional problems in the older population. Providing easy access to nutrition services in institutional and community-based health care settings will promote well-being in the older population. Evaluation of food and nutrition services should be routine and conducted with objective measurement techniques. It is important to review the available institutional and community-based health and social programs that serve older individuals and incorporate appropriate, professional nutrition services. The provision of an optimal mix of nutrition services will require significant changes in state regulations and modifications in current program operations. As future health policies develop, the appropriate types and levels of nutrition services are important to consider. The potential benefits of nutrition services in the older population should stimulate the design of a coordinated system of nutrition services in the continuum of community and institutional services for the older population. PMID- 3107793 TI - Nutrition and immune function in the geriatric population. AB - Aging in experimental animals and in man is associated with a significant defect of helper/inducer T-lymphocytes. This quantity deficiency is paralleled by a qualitative deficiency of T-lymphocyte number and function. Similar defects have been observed in protein calorie malnutrition and zinc deficiency, and there is evidence that both may exist in the aged ill and perhaps even in aged healthy individuals. Nutritional support improves the immune defect in aged ill patients and it may be of value in improving this deficiency, even when administered to aged healthy subjects. PMID- 3107794 TI - Nutrition, aging, and the immunohematopoietic system. AB - Aging is associated with declines in immune and hematopoietic functions, which bear many similarities to those caused by protein-calorie malnutrition. This review describes the age-related decline in the immunohematopoietic system and discusses the potential modulatory role of nutrition in these changes. PMID- 3107795 TI - Immunosuppressive acidic protein in true histiocytic lymphoma. AB - Serum immunosuppressive acidic protein (IAP) was determined in patient with true histiocytic lymphoma. The change of serum level of IAP correlated well with the clinical course, i.e., increased at relapse and decreased during remission. Immunohistochemistry showed IAP was present in the cytoplasms of normal granulocytes and histiocytes but not in neoplastic histiocytes. PMID- 3107796 TI - The effect of dietary seaweeds on 7,12-dimethyl-benz[a]anthracene-induced mammary tumorigenesis in rats. AB - Six groups of female rats were fed diets containing 2% of one of six powdered seaweeds for 152 days and a basic diet for 59 or 60 successive days, and controls were fed the basic diet for the whole experimental period. The 7,12 dimethylbenz[a]anthracene was given to all rats intragastrically (20 mg/kg X 1), 27 days after the start of feeding. Diets with 3 weeds, Porphyra tenera (PT), Laminaria religiosa (LR) and L. japonica var. ochotensis (LO), showed an inhibitory effect on mammary tumorigenesis. Tumor incidences were 35% (7/20), 35% (7/20) and 50% (9/18), respectively, whereas that in the control group was 69% (20/29). There was a significant delay in the time to first palpable tumor in LR fed and PT-fed rats (P less than 0.01). As for the tumor weight per rat in each group, it was significantly lower in the LR-fed group with a weight of 1.6 g, as compared with that of 16.3 g in the control group (P less than 0.02). PMID- 3107797 TI - Importance of the duration of inhibition on intestinal carcinogenesis by difluoromethylornithine in rats. AB - The effect of the duration and sequence of inhibition of intestinal tumor formation in rats was studied to determine whether part time inhibition has any value. Four groups of male Sprague-Dawley rats were given 8 weekly s.c. injections of azoxymethane (AOM) 8 mg/rat. Three groups were given the inhibitor, difluoromethylornithine (DFMO) in the drinking water; one for the entire 26 weeks of the study, one for the first 13 weeks only, and one for the last 13 weeks. A control group was not given the inhibitor. While the continuous treatment group developed the least number of tumors per rat (1.5 vs. 5 for controls), still both groups given the inhibitor for just 13 weeks also developed fewer tumors than controls 5 vs. 3.2 (early treatment) and 5 vs. 2.8 (late treatment). These results show that part time inhibition, including its late application, does reduce intestinal tumor formation in rats. PMID- 3107798 TI - In vitro drug sensitivity studies in human transitional cell carcinoma of the bladder. AB - An in vitro clonogenic assay was used to study the activity of 3 established cytotoxic drugs and 3 experimental agents against a series of 33 human transitional cell carcinomas. Strict adherence to rigid colony size criteria gave very reproducible results with the 3 cytotoxic drugs (adriamycin, mitomycin C and thiotepa) and our sensitivity curves are of the form expected on the basis of past experience with tumour cell lines. The unexplained plateau form curves which have previously led to criticism of the assay were not seen. Resistant subpopulations were found only in poorly differentiated tumours. This modified assay was then used to test 3 experimental agents for activity against transitional cell carcinoma. Sulphopentosan, DMSO and retinoic acid all proved inactive in this system. PMID- 3107799 TI - Promotion of hepatocarcinogenesis by suxibuzone in rats initiated with 3'-methyl 4-dimethylaminoazobenzene. AB - Among phenylbutazone (PZ) and its related compounds, suxibuzone (SUX) caused the most extensive decrease in pyruvate kinase (PK) activity with lower toxicity. Therefore, we studied the effect of SUX on rat hepatocarcinogenesis to confirm our assumption that an agent which causes a prolonged decrease in PK activity in rat liver promotes hepatocarcinogenesis. For initiation rats were fed a diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) for 4 weeks. At the end of 53 weeks of the experiment the incidences of liver tumors were 14.3 and 70.0% in the rats fed basal diet and in the rats fed 0.5% SUX diet, respectively, after the initiation. No tumors were observed in rats fed the SUX diet without the initiation. The result shows that SUX promotes hepatocarcinogenesis and supports the above assumption. PMID- 3107800 TI - Magnetic polyethyleneimine (PEI) microcapsules as retrievable traps for carcinogen electrophiles formed in the gastrointestinal tract. AB - Semi-permeable magnetic microcapsules containing polyethyleneimine (PEI) have been developed as retrievable carcinogen traps. In vitro, the soluble core PEI and membrane both bound reactive substances of limited aqueous stability, such as from [14C]N-methyl-N-nitrosourea ([14C]NMU), and aqueous stable dyes of molecular weight up to 1000. The core/membrane location ratio of binding was dependent upon membrane characteristics of the microcapsule batch used. Microcapsules administered intragastrically to rats bound up to 0.006% of [14C]dimethylhydrazine ([14C]DMH) and 1.4% of [14C]NMU administered i.p. or intrarectally, respectively. Time-dependency of [14C]DMH binding was consistent with labelling of microcapsules within the small intestine. There were no detectable metabolites from [14C]DMH trapped within the colon, whereas binding of [14C]NMU indicated that microcapsules could bind transient species present within the colon in competition with the faecal bulk. These results indicate that this approach could be used to detect highly unstable and possibly genotoxic substances in situ, hitherto unknown, formed within the intestinal lumen. PMID- 3107801 TI - The metabolism in vitro of 7,12-dimethylbenz[a]-anthracene by human bone marrow. AB - The leukaemogenic polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]-anthracene (DMBA) has been incubated with human bone marrow cells. It was found that these cells could metabolise DMBA to a number of products and that the process was dependent upon incubation time and upon cell number. Different bone marrow fractions from the same individual formed different DMBA dihydrodiols. Evidence was obtained that suggested that conjugation of DMBA metabolites with glucuronic acid occurred during incubation with bone marrow cells. The differential site specific metabolism of DMBA by human bone marrow fractions may have implications for future epidemiological studies. PMID- 3107802 TI - Effects of progestins on growth of experimental breast cancer in culture: interaction with estradiol and prolactin and involvement of the polyamine pathway. AB - The role of progesterone either alone or in combination with other hormones in breast cancer growth is not well established. In these experiments, using the hormone-responsive N-nitrosomethylurea-induced rat mammary tumor grown in the soft agar clonogenic assay, we tested the colony-stimulating effect of progesterone and the synthetic progestin R5020 over a wide range of physiological and pharmacological concentrations (from 0.1 nM to 10 microM). Both progesterone and R5020 were found to have a significant colony-stimulating effect which was more pronounced in the absence of serum. The action of progesterone appeared to plateau at concentrations of 10 or 100 nM, whereas R5020 was maximally effective at lower concentrations (approximately 1 nM). A biphasic dose-dependent effect was occasionally seen both with progesterone and R5020 with a loss of colony stimulating effect at high concentrations. The combined administration of varying doses of progesterone (0.1, 1, 10, and 100 nM) and estradiol (10(-10) M and 10( 9) M) was found at times to potentiate and at times to decrease colony formation over that observed with the individual treatments. The former effect, when present, was usually seen with low doses of progesterone, while the latter was frequently observed with high concentrations (100 nM). No major potentiation or suppression of colony formation over individual treatments was observed when varying doses of progesterone (1, 10, and 100 nM) were added together with prolactin (50 ng/ml). The administration of the polyamine biosynthesis inhibitor alpha-difluoromethylornithine completely blocked the colony-stimulating effect of progesterone. The inhibitory effect of alpha-difluoromethylornithine was completely reversed in a dose-dependent fashion by exogenous administration of spermidine, thus implying a critical involvement of the polyamine pathway in progesterone action. PMID- 3107803 TI - Monoclonal antibodies to ethanol-induced rat liver cytochrome P-450 that metabolizes aniline and nitrosamines. AB - Hybridomas were prepared from mouse myeloma cells and spleen cells derived from female BALB/c mice that had been immunized with a partially purified ethanol induced rat liver cytochrome P-450 (P-450et). Monoclonal antibodies (MAbs) produced by the hybridomas were screened for binding to P-450et with a radioimmunoassay. Thirty-one independent hybrid clones produced MAbs that had a high affinity for P-450et. Each clone produced MAbs of a single subclass of the mouse immunoglobulins IgG1, IgG2a, IgM, or IgA. Ten of the 31 MAbs also immunoprecipitated P-450et as determined by Ouchterlony double-immunodiffusion analyses. One of the MAbs was tested for cross-reactivity with other rabbit and rat liver cytochromes P-450 and was found not to cross-react with rat liver P-450 induced by either phenobarbital, beta-naphthoflavone, or rabbit liver P-450LM2 or P-450LM4. Nine of the MAbs were tested for cross-reactivity with rat liver clofibrate-induced P-450, rat liver pregnenolone-16-alpha-carbonitrile-induced P 450, and a human liver P-450. All the MAbs showed no cross-reactivity except for one MAb which cross-reacted with both pregnenolone-16-alpha-carbonitrile and human P-450 and three MAbs which cross-reacted with human P-450. Three antigen precipitating MAbs and four nonprecipitating MAbs were tested for their effects on the aniline p-hydroxylase activity of liver microsomes of untreated rats and from rats treated with acetone, pyrazole, methylpyrazole, or imidazole. One of the seven MAbs tested, 1-91-3, inhibited enzyme activity of acetone-, pyrazole-, or methylpyrazole-induced microsomes by 54, 47, and 48%, respectively. This indicates that at least 50% of microsomal cytochrome P-450 aniline p-hydroxylase activity in the latter is a function of a P-450 enzyme that contained the epitope to which the MAb 1-91-3 is directed. With untreated and imidazole-induced microsomes, 32 and 21% inhibition of the enzyme activity was observed. In reconstituted systems containing phospholipid and NADPH-cytochrome P-450 reductase, MAb 1-91-3 inhibited aniline p-hydroxylase activity of purified ethanol-induced P-450et and acetone-induced P-450 by more than 90%. Nitrosodimethylamine demethylase activity of acetone-induced rat microsomes was inhibited by the various MAbs up to 77% and the activity of the purified acetone induced P-450 was inhibited up to 92%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3107804 TI - Xenogenization of a mouse lung carcinoma (3LL) by transfection with an allogeneic class I major histocompatibility complex gene (H-2Ld). AB - We investigated the tumorigenicity and immunogenicity of tumor cells transfected with an allogeneic class I major histocompatibility complex gene. A single clone (3LL/3) from a Lewis lung carcinoma in the C57BL/6 strain (H-2b) was cotransfected with a BALB/c genomic clone containing an H-2Ld gene and a bacterial neo gene conferring resistance to G418. Three Ld-positive, three Ld negative, and two Neor clones were selected by means of a 125I-protein A binding assay using an anti-H-2Ld monoclonal antibody. The antigenic expression of the H 2Ld gene products was only 20-40% on the Ld-positive clones compared with Meth-A tumor cells of BALB/c mice. The 50% lethal tumor dose of these clones in C57BL/6 mice was 5.6 X 10(6) in the Ld-positive clones, but only 1.3 X 10(5) in the 3LL/3 parent clone, 1.2 X 10(5) in the Neor clones, and 2.2 X 10(5) in the Ld-negative clones. The tumorigenicity of the Ld-positive clones was, therefore, reduced to less than 1/40 of that of the parent tumor cells. The decreased tumorigenicity of the Ld-positive clones was abrogated in mice irradiated with 600 rads. After inoculation and spontaneous regression of the viable Ld-positive clone cells, the mice acquired transplantation resistance against the challenge of a parental 3LL/3 tumor. However, the immunogenicity variation between Ld-positive, Ld negative, Neor, and 3LL/3 parent clones showed no statistical difference. These results indicate that tumor cells transfected with an allogeneic class I H-2 gene can express an H-2 foreign antigen, can regress in syngeneic hosts, and can induce antitumor transplantation resistance against the original tumors, although they are not able to enhance their immunogenicity. PMID- 3107805 TI - Mutagenicity, unscheduled DNA synthesis, and metabolism of 1-nitropyrene in the human hepatoma cell line HepG2. AB - The cell line HepG2 is derived from a well differentiated human hepatoblastoma, which retains many of the morphological characteristics of liver parenchymal cells. These cells at passages greater than 95 were found to metabolically activate carcinogens to genotoxic metabolites. The addition of 6.8 microM 1 methyl-3-nitro-1-nitrosoguanidine, 5.3 microM 4-nitroquinoline-N-oxide, and 4 20.3 microM 1-nitropyrene resulted in the induction of mutations at the HGPRT locus as determined by 6-thioguanine resistance. This is the first description of the induction of mutations in these cells. Additionally, unscheduled DNA synthesis in the presence of 4 mM hydroxyurea was increased by 9% with 5.3 microM 4-nitroquinoline-N-oxide, 57% with 13.6 microM 1-methyl-3-nitro-1 nitrosoguanidine, and 300% with 8.2 microM 1-nitropyrene. High performance liquid chromatographic analysis of metabolites formed following incubation of HepG2 with either [3H]-1-nitropyrene or [14C]benzo(a)pyrene demonstrate the occurrence of arene oxidation as well as nitroreduction. PMID- 3107806 TI - Events associated with mouse skin tumor promotion with respect to arachidonic acid metabolism: a comparison between SENCAR and NMRI mice. AB - NMRI and SENCAR, two stocks of mice commonly used in multistage skin carcinogenesis studies, were compared with respect to the effects of inhibitors of arachidonic acid metabolism for the following 12-O-tetra-decanoylphorbol-13 acetate (TPA)-elicited events: tumor promotion, DNA synthesis in vivo and in vitro, ornithine decarboxylase induction, and prostaglandin (PG) E2 synthesis. Previous work had shown that the cyclooxygenase inhibitor indomethacin enhanced TPA promotion in SENCAR mice. We report here that over the same dose range (50 to 200 micrograms) indomethacin caused a dose-dependent inhibition of promotion in NMRI mice. Significant reversal of this inhibition was achieved with concomitant application of 10 micrograms PGF2 alpha but not PGE2. DNA synthesis studies showed that low doses of indomethacin and flurbiprofen increased TPA-stimulated DNA synthesis in primary cultures from SENCAR mice; indomethacin suppressed this response in NMRI cultures. In vivo DNA synthesis studies showed the same pattern: indomethacin enhanced TPA-stimulated DNA synthesis in SENCAR mice but inhibited in NMRI mice. Other classes of inhibitors of arachidonate metabolism (i.e., the cyclooxygenase-lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid and phenidone and the phospholipase A2 inhibitor dibromoacetophenone) had inhibitory activity in vitro and in vivo in both stocks of mice. Indomethacin was found to inhibit TPA-induced ornithine decarboxylase activity to the same extent in both mice. Indomethacin was also very effective in inhibiting TPA-induced PGE2 synthesis in both stocks of mice. 5,8,11,14-Eicosatetraynoic acid and phenidone were likewise suppressive in both stocks of mice. It is concluded that the NMRI and SENCAR mice respond similarly to TPA with respect to promotion, DNA synthesis, ornithine decarboxylase induction, and PG synthesis. The difference appears to be in the degree of involvement of the lipoxygenase pathway. PMID- 3107807 TI - Selective cytotoxicity of 4-S-cysteaminylphenol on follicular melanocytes of the black mouse: rational basis for its application to melanoma chemotherapy. AB - We have previously shown that 4-S-cysteaminylphenol (4-S-CAP) causes a significant inhibition of in vivo melanoma growth. To clarify the mechanism of the in vivo antimelanoma effect, this study evaluated the cellular and subcellular changes of follicular melanocytes after s.c. administration of 4-S CAP on the lumbar areas of black and albino mice. 4-S-CAP produced a prompt, selective swelling and lysis of melanocytes, resulting eventually in the necrosis of melanocytes and the depigmentation of black hair follicles. None of the degenerative changes were seen in melanocytes and keratinocytes of control albino follicles. Comparison of melanocytes in black and albino follicles revealed that melanin synthesis is highly active in the melanocytes of black follicles while melanin and tyrosinase synthesis is not seen in the melanocytes of albino follicles. The findings indicate that the selective melanocytotoxicity of 4-S-CAP is manifested by lysis and necrosis of cells which are actively engaged in melanin synthesis. 4-S-CAP appears to provide a new modality for rational chemotherapy of malignant melanoma. PMID- 3107808 TI - Nutritional support of bone marrow transplant recipients: a prospective, randomized clinical trial comparing total parenteral nutrition to an enteral feeding program. AB - Although standard supportive care for bone marrow transplant (BMT) recipients includes total parenteral nutrition (TPN), it has not been shown that this is the most appropriate method of nutritional support. To determine whether current BMT recipients require TPN during the early recovery period, we conducted a prospective, randomized clinical trial comparing TPN and an individualized enteral feeding program (counseling, high protein snacks and/or tube feeding). Nutritional assessment included measurement of serum proteins, anthropometry, and body composition analysis. For the latter, total body water and extracellular fluid were measured by standard radioisotope dilution techniques and used to quantitate body cell mass and body fat plus extracellular solids (FAT + ECS). In 27 TPN patients, body composition 28 days after BMT, expressed as a percentage of baseline, was body cell mass, 100%, extracellular fluid, 108%, FAT + ECS, 108%, and in 30 enteral feeding program patients, was body cell mass, 93%, extracellular fluid, 104%, and FAT + ECS, 94%. Only the difference in FAT + ECS was statistically significant (p less than 0.01). Compared to the enteral feeding program, TPN was associated with more days of diuretic use, more frequent hyperglycemia, and more frequent catheter removal (prompted by catheter-related complications), but less frequent hypomagnesemia. There were no significant differences in the rate of hematopoietic recovery, length of hospitalization, or survival, but nutrition-related costs were 2.3 times greater in the TPN group. We conclude that TPN is not clearly superior to individualized enteral feeding and recommend that TPN be reserved for BMT patients who demonstrate intolerance to enteral feeding. PMID- 3107809 TI - Interactions of cis-diamminedichloroplatinum(II) with 1-beta-D arabinofuranosylcytosine in LoVo colon carcinoma cells. AB - Prior reports demonstrated more than additive cytotoxic effects of cis diamminedichloroplatinum(II) (CDDP) and 1-beta-D-arabinofuranosylcytosine (ara-C) in LoVo colon carcinoma cells. We have extended these findings by analyzing mechanisms that may underlie the effect of ara-C on CDDP-induced cytotoxicity. In contrast to a previous study, ara-C neither enhances DNA interstrand cross-link formation by CDDP nor affects the excision of platinum from DNA. Features peculiar to ara-C, such as its misincorporation into DNA, probably contribute since more than additive cytotoxic effects do not occur by combinations of CDDP with inhibitors of DNA synthesis that are not incorporated into DNA. Also, while ara-C does not significantly enhance the degree of inhibition of DNA synthesis caused by CDDP, the recovery of DNA synthesis after drug removal is significantly slowed when cells are exposed to both drugs. These findings contrast with those obtained with CDDP and aphidicolin (the latter agent resembles ara-C in competing with dCTP for binding to DNA polymerase alpha but, unlike ara-C, is not incorporated into DNA). Lastly, ara-C is incorporated into LoVo cell DNA undergoing replicative synthesis as well as into DNA undergoing repair synthesis after CDDP-induced induced DNA damage. PMID- 3107810 TI - Sequential appearance of anchorage independence, uncontrolled nuclear division and tumorigenicity in 7,12-dimethylbenz(a)anthracene-exposed rat tracheal epithelial cells. AB - Epithelial cell lines derived from rat tracheal implants 2 and 9 months after a 4 week exposure to 200 micrograms dimethylbenz(a)anthracene-beeswax pellets, and previously assayed for growth in soft agarose and tumorigenicity, were tested at the same time of subculture for cytochalasin B-induced multinucleation to determine the relationships between anchorage-independent growth, uncontrolled nuclear division, and tumorigenicity. The relationships among the three phenotypic markers could be separated into five distinct groups. Group I cell lines showed no growth in agarose, showed no cytochalasin-induced multinucleation, and formed no tumors in nude mice. Group II cell lines exhibited anchorage independence but were negative for the other markers. Group III cell lines were anchorage independent and exhibited a positive response to cytochalasin B (more than 10% of the cells had three or more nuclei), but were tumor negative. Group IV cell lines were positive for all three markers. Group V cell lines grew in soft agarose, were cytochalasin B negative, but formed tumors only 4 months after the cell inoculations. The 20 cell lines generated 2 months after carcinogen exposure distributed in the groups as follows: Group I, 20%; Group 2, 20%; Group III, 50%; Group IV, 15%; and Group 5, 10%. The 27 cell lines generated 9 months after carcinogen exposure distributed among the groups as: Group I, 4%; Group II, 18%; Group III, 26%; Group IV, 52% and Group V, 0%. The results indicate that: anchorage independence precedes the two other markers of growth autonomy; uncontrolled nuclear division appears as a separate property after anchorage independence and before tumorigenicity; tumorigenicity appears preferably in the cell populations that exhibit anchorage independence and uncontrolled nuclear division; and progression in growth autonomy occurs in the tracheal implants in vivo which can be detected in vitro as an increase in cell lines positive for the three phenotypic markers. PMID- 3107811 TI - Hormonal modulation of plasminogen activator: an approach to prediction of human breast tumor responsiveness. AB - We have determined that the primary reason for the frequently encountered poor survival of human scirrhous breast carcinomas in short-term (4 days) organ culture is mechanical injury to the tumor tissue during explant preparation. It was possible to minimize this injury by preparing 0.5-mm-thick slices using very sharp blades. This resulted in much improved preservation of tissue structure and function, as assessed by histology, DNA content, and enzyme synthesis and secretion. With the exception of insulin, which was always present in the culture medium, exogenous hormones, including estrogen, or serum did not further improve explant preservation. In rodent mammary tumors, growth in vivo and production of the serine protease plasminogen activator (PA) in organ culture are coordinately regulated by hormones, suggesting that PA may be a valuable indicator of tumor hormone responsiveness. We have now tested the effect of estrogen and other hormones on PA secretion in organ cultures of primary human breast carcinomas. We found that: modulation of PA by 17-beta-estradiol (10-8) M) occurred only in carcinomas which were positive for both estrogen and progesterone receptors; of 21 such tumors, 11 (52%) were responsive. Plasminogen activator was not modulated by estradiol in any of the 22 tumors which were negative for one or both receptors; hydrocortisone (10(-7) M) effectively inhibited, and 3,5,3'-L triiodothyronine (10(-8) M) and adenylate cyclase activators effectively stimulated PA in most breast tumors, regardless of their estrogen and progesterone receptor status. Prolactin (5 micrograms/ml) had no effect when tested alone; urokinase-type PA was found to be the principal PA produced by human breast tumors. Changes in its rate of synthesis and secretion and not in the content of PA inhibitors appeared to be the prevailing mechanism of enzyme regulation by hormones. In summary, short-term organ culture coupled with the use of PA as an index of response appears to be a promising approach to the study of hormone sensitivity of primary human breast carcinomas. PMID- 3107812 TI - Interaction of hyperthermia and metabolic inhibitors on the induction of chromosome damage in Chinese hamster ovary cells. AB - We have examined the chromosomal effects of heating asynchronously growing Chinese hamster ovary (CHO K1) cells in the presence of actinomycin D or cycloheximide. Actinomycin D was found to strongly potentiate the chromosome damaging effects of heat shock, an effect correlated with a strong nonadditive reduction in cell survival. In contrast, cycloheximide treatment reduced heat shock induced chromosome damage and resulted in a significant nonadditive increase in cell survival following heat shock. The different effects of these two inhibitors on chromosomal damage and cell survival are correlated in part with their effects on the rate of DNA synthesis during heat shock. The results suggest that an important aspect of the interaction of heat and metabolic inhibitors involves changes in cell cycle phase distribution of and/or progression through the S phase of the cell cycle induced by drug treatment prior to and during heat shock. The data indicate that the protective effect of cycloheximide in heat shocked cells may involve altered cell cycle progression and/or phase distribution of cells during hyperthermia. PMID- 3107813 TI - Hormones and multistage carcinogenesis. AB - Initiation, promotion and the role of hormones in carcinogenesis are viewed within the framework of a two-stage model for malignant transformation that has been shown by Moolgavkar and Knudson to be consistent with the main body of epidemiological and experimental data on carcinogenesis. It is argued that hormones influence carcinogenesis principally by clonal expansion or contraction of initiated or first-stage cells. The role of hormones in breast cancer and endometrial cancer is briefly discussed. PMID- 3107814 TI - From pathogenesis to hormone prevention of mammary carcinogenesis. AB - The study of an experimental model, the induction of breast carcinomas by administration of the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) to virgin rats, has allowed us to determine that the susceptibility of the mammary gland to a carcinogen depends upon its degree of differentiation at the time of exposure. The mostly undifferentiated gland of young virgin rats is highly susceptible due to the high proliferative rate of the terminal ductal structures or terminal end buds (TEBs), ready for differentiation into alveolar buds (ABs) which avidly bind the carcinogen. Complete differentiation through a full-term pregnancy renders the gland resistant to carcinogenesis due to the replacement of TEBs by lobules whose epithelium has a low proliferative rate and low DMBA binding. Although pregnancy is the most complete stimulus, differentiating the highly susceptible TEBs of the virgin female into more resistant lobules, administration of certain pituitary, ovarian or placental hormones considerably modifies the mammary gland structure, thus influencing its response to chemical carcinogenesis. The observation that contraceptive agents administered for a short period of time also exert a protective effect allows us to postulate that this model could be developed as a protocol for breast cancer prevention. PMID- 3107815 TI - Phase II trial of ifosfamide and mesna in advanced colorectal cancer. PMID- 3107816 TI - "Role of hexamethylmelamine in the treatment of ovarian cancer: where is the needle in the haystack?". PMID- 3107817 TI - [Modification of ouabain-induced arrhythmia test in anesthesized guinea pigs]. PMID- 3107818 TI - [Atherosclerosis and prostaglandins: new biochemical frontiers of a more rational therapy]. PMID- 3107819 TI - Aneurysm of the right ovarian vein--an unusual cause of pulmonary embolism. AB - This case reports a 23-year-old female who experienced a massive bilateral pulmonary embolism. The source of thrombi was found to be in a large saccular aneurysm of the right ovarian vein. The pulmonary emboli were treated by local infusion of streptokinase. The patient was cured after removal of the aneurysm by surgery. PMID- 3107821 TI - Formation of an undesirable guide wire loop with the Cope introduction set. PMID- 3107820 TI - First clinical results with a new caval filter. AB - A new percutaneous inferior venacaval filter was used in 15 patients. The filter is constructed of stainless steel wires formed into a helical basket and anchoring legs. It can be inserted through a 10F catheter in an antegrade or retrograde fashion and can also be retrieved percutaneously. In a follow-up period of up to 13 months, the filter was well tolerated. One patient died of recurrent embolism despite filter protection. Local thrombogenicity was noted in 2 patients, but no other side effects were observed. Short-term heparinization following filter insertion is advisable. Heparin coating of the filter is under evaluation. PMID- 3107822 TI - Failure of Ivalon to provide permanent hepatic arterial occlusion. AB - Ivalon (polyvinyl alcohol) is a commonly used embolic agent, generally considered to be permanent. In a patient with the carcinoid syndrome, embolization of hepatic metastases with Ivalon failed to produce permanent occlusion, and recurrent tumor was supplied by many of the same small arteries identified on the original arteriogram. Occasionally, Ivalon may have only a temporary occlusive effect. A possible explanation for this phenomenon is proposed. PMID- 3107823 TI - Technique for transfemoral percutaneous pulmonary angiography. PMID- 3107824 TI - Application of cold antibacterial prepping solution to the skin. PMID- 3107825 TI - What is an arteriovenous malformation? PMID- 3107826 TI - The use of the Fourier transform in cardiac digital angiography. AB - Digital angiography has achieved broad clinical application as a morphological imaging modality through the technique of temporal subtraction known as digital subtraction angiography (DSA). After applying the Fourier transform to the intensity time curves (ITC) of an angiographic sequence, we are able to produce both morphological and functional images. The resulting pictures show an improved signal-to-noise ratio, reduction of motion artifacts, easy application of phase synchronous subtraction, and integration and quantitative visualization of blood flow. The methods are demonstrated with nonselective angiograms and intravenous levocardiograms. Furthermore, when applied to angiographic sequences, the Fourier transform leads to a significant reduction in data without loss of important information. PMID- 3107827 TI - Could inspiratory apnea disturb left ventricular volume assessment by contrast angiography? AB - To assess the influence of postinspiratory apnea on the measurement of the left ventricular volumes, contrast ventriculography was performed on 19 patients during spontaneous breathing and then in postinspiratory apnea. Data obtained were similar for end diastolic volumes (81 +/- 29 ml/m2 vs. 83 +/- 25; NS), end systolic volumes (35 +/- 20 ml/m2 vs. 34 +/- 19; NS), systolic index (46 +/- 13 ml/m2 vs. 49 +/- 12; NS), and ejection fraction (0.57 +/- 0.11 vs. 0.59 +/- 0.12; NS). Postinspiratory apnea suppressed the overlapping of the left ventricle with abdominal viscera in 15 of 17 patients. Diaphragmatic immobility permitted the assessment of regional left ventricular function in all 19 patients. However, pressures recorded in inspiratory apnea can no longer be compared to a transmural pressure, and, to assess ventricular compliance, intrapleural pressure must be measured simultaneously. We conclude that left ventricular volume assessment by contrast ventriculography is not disturbed by inspiratory apnea. This maneuver improves the quality of the images and allows a better evaluation of left ventricular segmental function. Spontaneous breathing can be recommended to simplify left ventricular compliance study. PMID- 3107829 TI - Steel coil embolization of hepatoportal fistulae. AB - Two patients with portal hypertension secondary to hepatoportal fistulae, of nontraumatic origin, were treated by transcatheter embolization of feeding hepatic artery branches with Gianturco-Anderson-Wallace steel coils. Both patients demonstrated immediate improvement of the symptoms related to their portal hypertension, 1 patient needing no further treatment after 3 years. It is concluded that using steel coils for this purpose is more effective and safer than other materials such as Gel-foam, and may cure portal hypertension in some cases. PMID- 3107828 TI - DSA--control of implanted devices for arterial hepatic perfusion. AB - In contrast to conventional film angiography, the perfusion pattern of hepatic arterial chemotherapy was consistently visualized by DSA in 40 patients with implanted Infusaid pump or Port-A devices. Incomplete perfusion of a liver region by the cytotoxic agent was recognized by DSA as accurately as by nuclide scintigraphy. Furthermore, DSA appeared to be more sensitive in determining aberrantly perfused extrahepatic regions; this was especially true when there was a nonligated right hepatic artery. Specific details of vascular lesions and associated complicating events also could be satisfactorily analyzed by DSA only. PMID- 3107830 TI - Peripheral embolization of diffuse hepatic arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia. AB - Ivalon particles were used for hepatic arterial embolization of diffuse arteriovenous malformation in a patient with hereditary hemorrhagic telangiectasia. The methods of the procedure and possible complications are discussed. PMID- 3107831 TI - CT demonstration of an aortoesophageal fistula. AB - A case of aortoesophageal fistula (AEF) is reported in a patient with esophageal bleeding resulting from ingestion of a foreign body. CT showed a saccular aneurysm in close proximity to the esophageal lumen at the level of the bleeding site. AEF has not previously been described on CT. PMID- 3107832 TI - New technique for left adrenal vein catheterization. AB - A technique for left adrenal vein catheterization utilizing a Mikaelsson catheter is described. This technique allows a stable catheter position within the left adrenal vein and permits bilateral adrenal vein catheterization using a single catheter. PMID- 3107833 TI - Unilateral left leg edema: a variation of the May-Thurner syndrome. AB - A single patient with left leg edema was examined with venography and computed tomography. A tortuous left common iliac artery was found to be compressing the left common iliac vein, causing near total obstruction of the left iliac vein. Hemodynamic pressure measurements confirmed the significance of the obstruction. PMID- 3107834 TI - Low-dose streptokinase thrombolysis of axillary-subclavian vein thrombosis. AB - Nine patients with 10 episodes of acute axillary-subclavian vein thrombosis were treated with local low-dose streptokinase infusion. All patients except one were heparinized during the procedure with conversion to oral anticoagulation upon completion of the infusion. Recanalization was achieved in 7 patients (70%). Thrombosis recurred in 1, and in 2 patients the procedure was unsuccessful. No major complications were encountered. We concluded that local low-dose streptokinase infusion is a safe, simple, and effective method for treating acute axillary-subclavian vein thrombosis. PMID- 3107835 TI - The role of CT in the management of pelvic arteriovenous malformations. AB - Four cases of pelvic arteriovenous malformations (AVM) were diagnosed and managed by CT, angiography, and embolotherapy. CT was used to determine the size, extent, and vascularity of each AVM and the involvement of adjacent organs. Thus CT was pivotal in the choice between surgical extirpation or embolotherapy. CT was also useful in monitoring patients following therapy. PMID- 3107836 TI - Dosage trial of a combination of oxamniquine and praziquantel in the treatment of schistosomiasis in Zimbabwean schoolchildren. PMID- 3107837 TI - Prolactin in cluster headache: diurnal secretion, response to thyrotropin releasing hormone, and relation to sex steroids and gonadotropins. AB - The diurnal rhythmicity of serum prolactin (PRL) and the PRL and thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) were studied in 31 cluster headache patients (4 chronic cases) and 14 healthy controls. Sixteen of the patients were studied both during clinical remission and headache periods. In males the nocturnal PRL peak was blunted during remissions as compared with that in cluster periods and that in control individuals. The 24-h mean PRL levels were lower during remission and cluster periods than in the controls. There were no significant differences in the PRL levels between female patients and controls. Headache attacks were often associated with increases of serum PRL levels. The PRL response to TRH was lower in the female patients but not in the male patients as compared with controls. The maximum testosterone levels were lower during cluster periods than during clinical remission but not when compared with controls. Serum levels of luteinizing hormone, follicle-stimulating hormone, progesterone, estradiol, T3, T4, and TSH did not differ between patients and controls. The results suggest an altered regulation of PRL secretion not only during active cluster periods but also during symptom-free intervals. The possible influence of sleep, estradiol, testosterone, medication, pain, and serotoninergic and dopaminergic mechanisms are discussed. PMID- 3107838 TI - pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane. AB - CD4 functions as the cell-surface receptor for human immunodeficiency virus (HIV); however, the mechanism of virus entry into susceptible cells is unknown. To explore this question we used a human T lymphoblastic cell line (VB) expressing high levels of surface CD4. Neutralization of endosomal compartments (pH greater than 6.4) with lysosomotropic agents did not effectively inhibit HIV nucleocapsid entry into the cytoplasm, and virus treated at low pH (5.5) failed to induce rapid cell-to-cell fusion in uninfected cells. Electron microscopy of VB cells acutely exposed to HIV at neutral pH revealed direct fusion of the virus envelope with the plasma membrane within minutes at 4 degrees C. No endocytosed virions were visualized upon rewarming the HIV-exposed cells to 37 degrees C for as long as 60 min. These results indicate that HIV penetrates CD4-positive T cells via pH-independent membrane fusion. PMID- 3107839 TI - Cycling of the integral membrane glycoprotein, LEP100, between plasma membrane and lysosomes: kinetic and morphological analysis. AB - LEP100 (an integral membrane glycoprotein, Mr = 100,000) occurs in three subcellular compartments: lysosome (approximately 90% of the molecules), endosome (5%-8%), and plasma membrane (2%-3%). Rate constants for movement to and from each compartment have been estimated. The movement of LEP100 from endosomes to lysosomes was blocked by chloroquine, causing redistribution to a new steady state in which about 30% of LEP100 molecules were localized in clathrin-coated patches on the cell surface, while intracellular LEP100 occurred in nearby endocytic vesicles. The cell-surface and endosomal pools of LEP100 remained in rapid equilibrium (t1/2 about 5 min). These results support the existence of a hitherto unappreciated pathway of membrane flow from lysosomes. The lysosome should not be considered simply a terminal target of membrane trafficking. PMID- 3107840 TI - Germ line and soma cooperate during oogenesis to establish the dorsoventral pattern of egg shell and embryo in Drosophila melanogaster. AB - Mutations in gurken and torpedo cause a ventralization in the follicle cell epithelium during Drosophila oogenesis and in the pattern of the embryo that develops in the resultant egg. Both genes lie midway in an epistatic series between fs(1)K10 and dorsal; the mutations block the dorsalization normally observed in K10 eggs but have no effect on the phenotype of embryos derived from dorsal mothers. Analysis of germ-line mosaics demonstrates that both ovarian and embryonic phenotypes will be produced when either the gurken+ gene is removed from the germ line or torpedo+ is removed from the soma. This shows that the dorsoventral pattern of the Drosophila egg chamber depends on the transfer of spatial information from the germ line to the somatic follicle cells, and from somatic cells to the oocyte. PMID- 3107841 TI - Lectin binding and inhibition studies reveal the importance of D-glucose, D mannose and N-acetylglucosamine during early sexual development of Dictyostelium discoideum. AB - Fluorescein-conjugated and non-conjugated lectins were used to determine which surface sugars are involved in the early events of sexual (macrocyst) development in Dictyostelium discoideum. Only zygote giant cells showed unique binding of FITC-WGA and FITC-PNA while all cell types (amoebae, gametes, binucleates, giant cells) showed identical patterns of FITC-Con A, -Gorse and -RCA II binding. In spite of its non-selective labelling of all cell types, Con A inhibited macrocyst formation. The temporal addition of Con A with and without specific hapten sugars indicates the importance of both D-mannose and D-glucose in phagocytosis and, possibly, cell fusion. WGA also inhibited macrocyst formation. Varying the time of addition of the lectin plus/minus its primary hapten sugar implicates N acetylglucosamine as being important in cell fusion. Neither Gorse, RCA II nor PNA had any detectable inhibitory effects on macrocyst development leaving the appearance of increased PNA receptors at the giant cell surface as an enigma. PMID- 3107842 TI - Angiotensin II is chemotactic for a T-cell subset which can express migration inhibition factor activity in murine schistosomiasis mansoni. AB - In murine schistosomiasis mansoni, ova induce a delayed-type hypersensitivity, granulomatous response in which angiotensins are produced. Angiotensin II (AII) elicits a chemotaxis for splenic mononuclear cells derived from these infected animals. The effect of AII upon the migration of a T-lymphocyte subset was defined functionally to further delineate this observation. A chemotaxis chamber was developed that permitted collection of large numbers of viable cells which migrate in response to AII. In a direct migration inhibition factor (MIF) assay, MIF activity was demonstrated with 100-fold fewer chemotactically attracted cells as opposed to whole splenic leukocytes. The MIF activity was eliminated by treatment of the cells with anti-Lyt 1.1 or-Thy 1.2 serum and complement. This observation was particularly interesting since migrated and whole spleen cell populations comprised equal numbers of T cells. Incubation of spleen cells with AII prior to assay did not alter MIF activity. These findings suggest that AII is chemotactic for at least one important T-cell subset relevant to the granulomatous response. PMID- 3107843 TI - The role of lymphokine-activated cell-associated antigen. III. Inhibition of T cell activation by monoclonal killer-blocking antibody. AB - The addition of monoclonal killer blocking antibodies (KBA MAb) to cultured T cells resulted in significant inhibition of T-cell responses to concanavalin A (Con A), class I antigen and class II antigen, whereas T-cell responses to phytohemagglutinin are insensitive to KBA MAb. The inhibitory effect of KBA MAb is observed only when KBA MAb is added to the culture at an early time. This indicates that the lymphokine-activated cell-associated antigen (LAA) defined by KBA MAb plays an important role in the early stages of T-cell activation. Con A induced interleukin 2 (IL-2) receptor acquisition and IL-2 production, both of which are required for the early steps of T-cell activation, were greatly inhibited by KBA MAb. However, KBA MAb did not inhibit the action of IL-2, which is required for later stages of T-cell activation. PMID- 3107844 TI - Oxygen radicals in brain injury. AB - Experimental fluid percussion brain injury in anesthetized cats causes vascular injury characterized by sustained arteriolar dilation, abnormal reactivity to vasoconstrictor and vasodilator interventions, focal endothelial lesions, and reduction of the oxygen consumption of the vessel wall. These abnormalities are minimized or completely inhibited by pretreatment with cyclooxygenase inhibitors or with oxygen radical scavengers. They were therefore ascribed to oxygen radicals generated in the course of accelerated arachidonate metabolism via cyclooxygenase. Following this type of brain injury, there is an increase in the activity of phospholipase c in the brain and a transient increase in brain concentration of prostaglandins. Superoxide anion radical was detected in the extracellular space of the brain both immediately following brain injury as well as one hour afterwards as the superoxide dismutase inhibitable portion of nitroblue tetrazolium reduction. The sustained dilation and abnormal reactivity of cerebral arterioles following brain injury were also reversed by superoxide dismutase and catalase applied on the brain surface 30 minutes after injury. These results suggest that treatment with oxygen radical scavengers might be effective in inhibiting or reversing some of the effects of brain injury, even though the intervention with the therapeutic agents occurs sometime after the injury has taken place. PMID- 3107845 TI - [Personal experience with ovarian stimulation in an in vitro fertilization and embryo transfer program]. PMID- 3107846 TI - The effect of ketamine anaesthesia on the acidotic fetal lamb. AB - The following study in pregnant ewes was done to examine the effects of ketamine oxygen anaesthesia on the fetal lamb made acidotic by partial occlusion of the umbilical cord. Fifteen pregnant ewes were instrumented under general anaesthesia to allow continuous measurement of maternal and fetal mean arterial pressure and pulse rate and for withdrawal of arterial blood samples for blood gas analysis. An occlusion loop was loosely secured around the umbilical cord. Following a recovery period of 48 hours, a tracheostomy was performed on each ewe. After a control period, the umbilical occlusion loop was slowly inflated until fetal pH had decreased to 7.12-7.15. Following inflation the animals were divided into groups A and B. Group A received no anaesthesia. In Group B, the ewes received ketamine 3 mg X kg-1 intravenously and controlled ventilation with FIO2 of 1.0. After ten minutes ketamine 1 mg X kg-1 was given. In both groups radioactive microspheres were injected into the fetus at 0, 5, and 15 minutes. Ketamine anaesthesia in the pregnant ewe abolished the fetal hypertension and bradycardia produced by partial cord occlusion. All fetuses survived the 15 minutes of ketamine anaesthesia and there were no significant changes in arterial blood gases or pH. Blood flows determined by the microsphere method to the brain, heart, and kidneys were not significantly altered by ketamine. We conclude that ketamine-oxygen anaesthesia does not cause further deterioration in the acidotic fetal lamb. PMID- 3107847 TI - Water-contact patterns and socioeconomic variables in the epidemiology of schistosomiasis mansoni in an endemic area in Brazil. AB - A study was carried out in Comercinho in south-east Brazil where information relating to socioeconomic factors and water contacts was obtained from 290 (99% of the total) households and 1208 (82% of the total) inhabitants, respectively. Stool examinations and physical examinations were performed on 90% and 82% of the population, respectively. The rates of Schistosoma mansoni infection and splenomegaly were higher in families whose heads were manual workers, in individuals living in houses without piped water and of poor construction, and in those who were born in Comercinho. A total of 1017 (84%) individuals reported water contact; 75% of these contacts were for household activities or bathing and 21% for leisure. The faecal egg counts decreased in persons over 15 years of age, while the degree (intensity) of water contact did not. The mean degree of water contact was higher in individuals without than with piped water in the household (96.8+/-0.6 v. 25.7+/-0.6). The main risk factors for splenomegaly weer no piped water, intense water contact, bathing in streams, and daily contact (odds ratio=7.3, 5.1, 4.5 and 3.6, respectively). These results indicate that the extension of piped water to houses should decrease the incidence of splenomegaly in this endemic area. PMID- 3107848 TI - Interferon-gamma and cytotoxic agents studied in combination using a soft agarose human tumor clonogenic assay. AB - The in vitro antiproliferative activity of human recombinant interferon-gamma (IFN-gamma) was tested against human tumor cells in vitro in combination with doxorubicin, cisplatin, or vinblastine. Using a human tumor clonogenic assay (HTCA), IFN-gamma alone showed dose-dependent inhibition of colony growth in six or seven human tumor cell lines as well as in each of nine fresh ovarian tumor specimens. The combination of IFN-gamma and either doxorubicin or cisplatin showed additive antiproliferative effects against all the cell lines with the exception of an IFN-gamma-resistant endometrial cancer cell line (HEC-1A). In combination with vinblastine, IFN-gamma rarely had an additive effect. Inclusion of macrophages from malignant effusions in the HTCA potentiated the antiproliferative effect of IFN-gamma alone as well as the combination of IFN gamma and doxorubicin; however, the efficacy of the two agents was never more than additive. The results show that combinations of IFN-gamma with doxorubicin or cisplatin are additive and warrant further investigation. The antitumor effect of IFN-gamma alone or in combination with cytotoxic drugs may be significantly enhanced by tumor-associated macrophages. PMID- 3107849 TI - 5-fluorouracil, adriamycin, and mitomycin-C (FAM) chemotherapy in advanced adenocarcinoma of the lung: comparison of two dosage schedules. AB - Fifty patients with inoperable adenocarcinoma of the lung were randomized in a prospective study to receive either standard doses or high doses of 5 fluorouracil, adriamycin, and mitomycin-C (FAM versus Hi-FAM). The response/stabilization rate was 32% for FAM and 34% for Hi-FAM (P greater than 0.05), and the median survival was 27 weeks for FAM group and 24 weeks for Hi-FAM group (P greater than 0.05). Myelotoxicity was mild in FAM, but moderate to severe in Hi-FAM. It is concluded that Hi-FAM did not yield a higher response rate or median survival compared with FAM, but caused significantly more severe myelotoxicity. PMID- 3107850 TI - Macromolecular binding of the thyroid carcinogen 3-amino-1,2,4-triazole (amitrole) catalyzed by prostaglandin H synthase, lactoperoxidase and thyroid peroxidase. AB - 3-Amino-1,2,4-triazole, a thyroid carcinogen and goitrogen, is negative in a wide variety of short-term mutagenicity assays. However, amitrole induces gene mutations and morphological transformation in Syrian hamster embryo fibroblasts, cells known to carry out the prostaglandin H synthase (PHS)-mediated peroxidative metabolism of other carcinogens. Therefore, we have investigated the peroxidase mediated binding of [14C]amitrole to macromolecules in vitro. We report here the PHS- and lactoperoxidase-catalyzed binding of [14C]amitrole to protein and tRNA, as well as protein binding by rat and hog thyroid peroxidase. PHS was an order of magnitude more active than lactoperoxidase and two orders of magnitude more active than thyroid peroxidase. The low levels of binding observed with thyroid peroxidase could be explained by the rapid and potent inhibition of this enzyme by amitrole. Although the thyroid peroxidase-mediated binding of amitrole was quite low, it was not inhibitable by compounds that would be expected to be competing substrates in vivo (i.e. I-, monoiodotyrosine, diiodotyrosine). Neither catalase nor horseradish peroxidase catalyzed binding of [14C]amitrole. It was also observed that an interaction between amitrole and protein and/or nucleic acid resulted in the slow generation of hydrogen peroxide, which then served as a substrate to drive peroxidase-mediated binding of [14C]amitrole. These data suggest that PHS may be responsible for conversion of amitrole to a mutagenic intermediate in Syrian hamster embryo cells. Furthermore, the generation of reactive metabolites of amitrole by thyroid peroxidase and/or PHS may contribute to the complete carcinogenicity of this compound by adding a mutagenic response to its potent hormonal effects. PMID- 3107851 TI - Stereoselective metabolism of benzo[c]phenanthrene to the procarcinogenic trans 3,4-dihydrodiol. AB - The enantiomeric compositions of benzo[c]phenanthrene trans-3,4-dihydrodiol, a metabolic precursor of the ultimate carcinogenic bay-region 3,4-dihydrodiol-1,2 epoxides, formed in the metabolism of BcPh by liver microsomes from untreated, phenobarbital (PB)-treated, 3-methylcholanthrene (MC)-treated and polychlorinated biphenyls (PCB; Aroclor 1254)-treated rats of the Sprague-Dawley and Long-Evans strain were each determined by chiral stationary-phase h.p.l.c. and circular dichroism spectral analyses. The percentage of 3R,4R enantiomer in the trans-3,4 dihydrodiol metabolite of BcPh varies, depending on the concentration of liver microsomal enzymes used and the time of incubation: 29-30% (control), 46-54% (PB), 94-100% (MC) and 90-99% (PCB). PMID- 3107852 TI - Early stimulation: psychomotor development of two girls with Aicardi syndrome. AB - The psychomotor development achieved by two girls with the Aicardi syndrome is described. Until now this syndrome has been considered to produce a total dissociation from the environment in those affected. The results of early intervention, although not spectacular, are sufficient to recommend early stimulation in these children. PMID- 3107853 TI - Renal microthrombosis following endotoxin infusion may be mediated by lipoxygenase products. AB - Renal microvascular thrombosis following endotoxin infusion was assessed by measuring accumulation of 125I-labeled fibrinogen and transmission electron microscopy. Endotoxin shock was induced in unanesthetized Sprague-Dawley rats using 14 mg/kg Escherichia coli endotoxin (Difco) infused intravenously over a 5 hour period. Fifteen minutes after infusion of endotoxin was started, intravenous treatment was initiated. Two-thirds of the treatment was given over a period of 20 minutes followed by the remaining dose over the next 2 hours. Five rats received methyl prednisolone sodium succinate (Solu-Medrol) (U-9,088) (39.5 mg/kg). Six rats received a Solu-Medrol analog (methyl prednisolone 21(N Methyltaurosuberate), sodium salt) (U-67,590A) (61.08 mg/kg). Six rats received a 5-lipoxygenase inhibitor (1-naphthalenol,2,3,diethyl-4-methoxy-acetate) (U 66,855) (20 mg/kg). Six rats received a prostacyclin analog (pentanoic acid, 5- less than hexahydro-5-hydroxy-6-(3-hydroxy-1-octenyl)-3a-methyl-2(1H)- pentalenylidene greater than -calcium salt, hydrate) (U-61,431F) (0.04 mg/kg). Six rats received a thromboxane synthase inhibitor (2-benzofurancarboxylic acid, 5-(3-pyridinylmethyl), sodium salt monohydrate) (U-63,557A) (18 mg/kg). Eight endotoxin-infused rats received only normal saline. Six control rats received no endotoxin infusion, only saline. Composition and location of thrombi were assessed by transmission electron microscopy. Glomerular thrombosis was quantitated by determination of whole blood equivalents of 125I fibrin/g of tissue. Electron microscopy and radioactive quantitation demonstrated microthrombosis in the nontreated endotoxin group. The thrombi contained fibrin, platelets, erythrocytes, and leukocytes. The extent of thrombosis was significantly elevated compared to saline-treated controls. Three treated groups (U-9,088, U-67,590A, and U-66,855) all had significantly less thrombosis than the nontreated endotoxin rats. Two treated groups (U-63,557A and U-61,431F) developed glomerular thrombosis similar to untreated endotoxin rats. The results suggest that endotoxin stimulation of procoagulant activity and microthrombosis may be mediated by production of arachidonic acid metabolites via the lipoxygenase pathway. PMID- 3107854 TI - ELISA for determination of albumin in the nanogram range: assay in cerebrospinal fluid and comparison with radial immunodiffusion. AB - An ELISA double antibody sandwich technique on polystyrene microtiter plates for quantitation of albumin in cerebrospinal fluid is described. Commercially available reagents are used for this assay, in which albumin in the range between 0.1-1 ng/100 microliters can easily be detected. Albumin determinations in 30 CSF samples by this method revealed concentrations of 0.1-0.8 mg/ml. Results obtained by ELISA correlated significantly with those from parallel experiments with commercially available RID assays. The ELISA described is a sensitive, simple, and expeditious assay for determination of albumin in the nanogram range and may be a promising method for routine analysis of albumin concentrations in CSF. PMID- 3107855 TI - Effects of exogenous beta-galactosidase on cultured fibroblasts with beta galactosidase deficiency. PMID- 3107856 TI - Immunological comparison of biotinidase in serum from normal and biotinidase deficient individuals. AB - An antiserum specific to enzymatically active human serum biotinidase was prepared. Using this antiserum, two immunologically cross-reacting protein fractions, only one of which corresponds to the active enzyme, were observed in sera from individuals with normal biotinidase activity. Neither of these protein fractions was detected in sera from 18 individuals with biotinidase deficiency from 15 families. PMID- 3107857 TI - Inhibition of sympathetic constriction of the ex vivo tail artery perfused with blood from rats given frusemide. AB - Blood was withdrawn at a constant rate from the cannulated carotid artery of an anaesthetized rat and perfused an ex vivo segment of tail artery cannulated at both ends and contained in an organ bath. Blood returned to the rat via a cannulated jugular vein. The tail artery was constricted and perfusion pressure increased by peri-arterial stimulation at 5 Hz for 5 s every 2 min. Intravenous frusemide (5 mg/kg) decreased the stimulation responses of the tail artery. Diuresis-induced volume losses after frusemide were circumvented by a urinary bladder-intravenous shunt. Frusemide-induced reduction of tail artery vasoconstrictor responses was not seen in nephrectomized rats nor in rats pretreated with indomethacin or saralasin. Indomethacin did not change responses already reduced by frusemide. Exogenous arachidonate or angiotensin II infused into the blood perfusing the tail artery did not alter stimulation responses. We conclude that intravenous frusemide administration to a rat reduces sympathetic vasoconstrictor responses of the ex vivo blood perfused tail artery segment by a diuresis-independent but prostaglandin and angiotensin II dependent release of another hormone from the kidney. PMID- 3107858 TI - Nutritional and metabolic consequences of extensive bowel resection. PMID- 3107859 TI - Platelet hyperaggregability in the nephrotic syndrome which is not dependent on arachidonic acid metabolism or on plasma albumin concentration. AB - In 20 patients with nephrotic syndrome we confirm previous findings of in vitro platelet hyperaggregability to arachidonic acid, and describe similar hyperaggregability to ristocetin. As previously reported also, the addition of albumin to nephrotic platelet-rich plasmas corrected platelet hyperaggregability to arachidonic acid, but exerted little effect on ristocetin-induced aggregation, and there was no correlation between platelet aggregation thresholds to arachidonate and to ristocetin. Incubation with indomethacin abolished the generation of thromboxane B2 after stimulation with arachidonate, but had no effect on the stimulation with ristocetin, during which no TxB2 was produced. The nephrotic patients had elevated factor VIII-related antigen (Factor VIII R:Ag) concentrations in their plasma, but in addition both decreased serum IgG and platelet-associated IgG were found which were correlated. The hyperaggregability of nephrotic platelets to ristocetin may relate to the elevated factor VIII R:Ag levels, or to the low platelet-associated IgG, since platelet IgG Fc receptors and von Willebrand factor receptors are spatially close or identical. PMID- 3107860 TI - Renal biopsy in Fabry's disease eight years after successful renal transplantation. AB - Late graft histology after renal transplantation for Fabry's disease has only once been previously reported. Clinical data and kidney biopsy findings in a case of Fabry's disease before and eight years after successful kidney transplantation are presented. The graft maintains normal function. Graft histology in light microscopy showed no abnormalities reminiscent of the diseased native kidney. Electron microscopy revealed occasional small myelin figures which were present only in the vascular endothelium. Their significance and a review of conflicting reports and opinions from the literature are discussed. PMID- 3107861 TI - Economic evaluation of extracorporeal shock wave lithotripsy, percutaneous ultrasonic lithotripsy, and standard surgical treatment of urolithiasis--a Canadian perspective. AB - In order to provide information for decision making regarding urolithiasis treatment programs for the population of the Central West Region (population 1.8 million) of Ontario, we conducted an incremental cost-effectiveness analysis of standard surgery, percutaneous ultrasonic lithotripsy, and extracorporeal shock wave lithotripsy for the removal of renal and ureteric stones. Estimates of costs and effects were calculated for a 5-year period, beginning in 1985. Direct medical costs estimated were fees, both professional and technical, operating costs, and hospitalization costs for standard surgery, percutaneous ultrasonic lithotripsy, and extracorporeal shock wave lithotripsy. Capital costs, opportunity costs, and depreciation were included for extracorporeal shock wave lithotripsy, but not for standard surgery or percutaneous ultrasonic lithotripsy, thus creating a bias against extracorporeal shock wave lithotripsy. All costs were expressed in 1985 Canadian dollars; both costs and effects from years 2-5 were discounted using a rate of 5%. The effects estimated were disability days. Failure rates, complication rates, length of hospital stay, and disability days were median values reported in the medical literature. Assuming 400 procedures per year (based on previous experience in the Central West Region), the total 5 year costs in millions of dollars, were 8.86 for standard surgery, 7.84 for extracorporeal shock wave lithotripsy, and 7.51 for percutaneous ultrasonic lithotripsy. Costs per procedure were 4,429 for standard surgery, 3,918 for extracorporeal shock wave lithotripsy, and 3,756 for percutaneous ultrasonic lithotripsy. The total disability days generated were 69,098 for standard surgery, 18,184 for percutaneous ultrasonic lithotripsy, and 9,092 for extracorporeal shock wave lithotripsy. Because standard surgery costs more and generates more disability days than either percutaneous ultrasonic lithotripsy or extracorporeal shock wave lithotripsy, it is clearly the least desirable alternative. At 400 procedures per year, the cost of each disability day averted by extracorporeal shock wave lithotripsy, compared to percutaneous ultrasonic lithotripsy, is $35.60. At 500 procedures per year, extracorporeal shock wave lithotripsy costs less and generates fewer disability days than percutaneous ultrasonic lithotripsy and is therefore the desired alternative. Sensitivity analyses demonstrate that cost effectiveness results are most affected by the number of procedures performed, the length of stay, and the number of disability days generated. PMID- 3107862 TI - Calcinosis at the site of leakage from extravasation of calcium disodium edetate intravenous chelator therapy in a child with lead poisoning. AB - Painful calcinosis appeared at the wrist of an eight-year-old girl with lead poisoning. Careful history revealed that calcification occurred at the site of previous extravasation of calcium disodium edetate (EDTA) used in chelation therapy. Light microscopic, ultrastructural, electron activation, and X-ray diffraction studies demonstrated apatites with some suggestion of an admixture of octacalcium phosphate. PMID- 3107863 TI - Heterotopic ossification and pseudoarthrosis in the shoulder following encephalitis. A case report and review of the literature. AB - Heterotopic bone formation, or myositis ossificans, is common, particularly following trauma, total hip arthroplasty, spinal cord injury, severe head injury, and long-term coma. Although the mechanism is unknown, the pathogenesis is assumed to depend on transformation of mesenchymal cells to bone forming cells in response to a variety of stimuli. The clinical findings, laboratory data, roentgenograms, and radionuclide studies are standard aids in the diagnosis of heterotopic ossification. The treatment usually consists of range-of-motion exercise, nonsteroidal antiinflammatory drugs, X-ray therapy, disodium etidronate (EHDP), and excisional surgery. Reported here is a rare case of periarticular heterotopic ossification in the shoulder of a 38-year-old woman following head injury and 13 months in a coma. The unusual feature was the development of a pseudoarthrosis within the heterotopic bone. The patient's shoulder became markedly stiff with the development of a heterotopic pseudoarthrosis. Excision of the heterotopic bone and pseudoarthrosis was performed to improve the range of motion. Clinical roentgenographic, radionuclide, and pathologic observations are presented on the formation of a synovial joint within the heterotopic bone. PMID- 3107864 TI - Liver scintigraphy in chronic hepatosplenic schistosomiasis. A predictor of disease severity. AB - Liver-spleen scintigrams were performed in 42 patients with chronic hepatosplenic schistosomiasis. The scan patterns found are described and classified in five stages of increasing hepatic involvement. The scintigraphic classification correlates well with clinical parameters of disease severity. With higher stages, the number of symptoms and the severity of complications increase. The liver spleen scan provides a simple and accurate means to determine extent of hepatic involvement and probabilities of complications in this disease. PMID- 3107865 TI - Scintigraphy of persistent vertebral transverse process epiphysis. AB - Two cases of increased scintigraphic activity in a persistent transverse process epiphysis are presented to illustrate the need to recognize this as a normal developmental variant. Differentiation from fracture or neoplasm usually can be made by correlative radiographic imaging. PMID- 3107867 TI - Neurofibromatosis. AB - Neurofibromatosis (NF) is an inherited disorder characterized by the development of a wide variety of clinical manifestations, including characteristic "freckle like" pigmentations (cafe au lait spots) that develop in infancy, followed by skin tumors that may vary widely in size, number, and distribution. In addition to skin tumors, bone, neurologic, and endocrine abnormalities are common. NF is recognized in eight different types, with clinical heterogeneity being the hallmark of this disease. Malignant degeneration of the tumor to neurofibrosarcoma is rare. Early diagnosis, genetic counseling, treatment of symptoms, and appropriate surgery are the tools available for management of NF patients. Surgical procedures generally involve judicious subtotal resection, combined with reconstructive efforts aimed at functional improvement and cosmesis. PMID- 3107866 TI - Digital swelling following long-term administration of prostaglandin E1 in an infant. AB - A premature infant with hypoplasia of the right heart and pulmonary arteries required treatment with prostaglandin E1 (PGE1) for 107 days prior to surgical intervention. Digital swelling was noted at 40 days of age. Swelling was measured by determining the ratio of the distal phalangeal depth to interphalangeal depth. The ratio declined from 1.16 to 0.94 in the first 64 days after treatment. We believe digital swelling is a reversible complication of PG therapy. PMID- 3107868 TI - Pseudomalignancies. AB - The plastic surgeon encounters a variety of lesions that are benign histologically, but malignant in terms of their manifestations and clinical course. Many of these desperate pathologic situations present exceedingly difficult problems in terms of their diagnosis and management. Clinical entities that tend to be grouped within this type of pathologic phenomenon include giant pigmented nevi, arteriovenolymphatic malformations, neurofibromatosis, and localized overgrowth. The authors examine such lesions on the basis of their presentations, pathogeneses, and pathophysiology. PMID- 3107869 TI - Changes in pulmonary venous pressure and albumin concentration during treatment of severe diabetic decompensation. AB - Pulmonary capillary wedge pressure (PCWP), serum albumin concentrations, and arterial oxygenation (PaO2) were monitored during crystalloid loading in 10 patients with severe decompensated diabetic states (SDDS). Rapid infusion of crystalloid induced marked rises in PCWP (median 6 mmHg, range 1-21 mmHg) and falls in albumin concentrations (median 5 g/l, range 0.8-15 g/l) over the first few hours of treatment. PaO2 was significantly related (r(s) = -0.25, p less than 0.05) to the calculated hydrostatic forces across the pulmonary capillary bed. However, hypoxaemia was found at initiation of therapy in 2 patients where calculated COP greatly exceeded PCWP. Hypoxaemia developing during crystalloid loading for SDDS may imply the formation of sub-clinical pulmonary oedema and the subsequent fluid replacement regimen should then be appropriately reviewed. PMID- 3107870 TI - A prospective study of cryoprecipitate administration: absence of evidence of virus infection. AB - In a prospective study of cryoprecipitate administration to patients who had never received large pool concentrates, no evidence of hepatitis or HIV infection was detected in a follow up period of one year. Following the introduction of screening of blood donors for anti-HIV in the UK in October 1985 the use of cryoprecipitate in selected cases should be reconsidered. PMID- 3107872 TI - In vitro activity of RO 23-6240 (AM-833): a new fluoroquinolone. AB - The in vitro activities of RO 23-6240 (AM-833) and four comparative fluoroquinolones were studied. Minimal inhibitory concentrations (MICs) of RO 23 6240, which inhibited at least 90% of strains, were less than or equal to 0.03-1 microgram/ml for Staphylococcus aureus, Staphylococcus epidermidis, Enterobacteriaceae, Acinetobacter anitratus Aeromonas hydrophila, Branhamella catarrhalis, and Haemophilus influenzae, 2-8 micrograms/ml for Staphylococcus saprophyticus, streptococci, diphtheroids, and Pseudomonas spp., and 1-32 micrograms/ml for anaerobic species. MICs of ofloxacin, pefloxacin, norfloxacin, and ciprofloxacin paralleled those of RO 23-6240. With all five drugs, MICs were minimally affected by inoculum size and minimal bacterial concentrations (MBCs) were always within two dilution steps (log2) of MICs. PMID- 3107873 TI - Molecular biology of Homo sapiens. PMID- 3107871 TI - Binding and antibody blocking effects of intravenous IgG preparation on peripheral blood cells. AB - The mode of action of high dose intravenous gammaglobulin (IVGG) in idiopathic thrombocytopenic purpura (ITP) is controversial. This study used immunofluorescence techniques to investigate the possibility that IVGG binds to peripheral blood cells and that such binding blocks attachment of cell specific autoantibodies. IVGG bound to platelets, neutrophils, monocytes and lymphocytes. Erythrocytes appeared to bind only anti-A and anti-B present in the IVGG. Multimeric and monomeric fractions of IVGG also bound to these cells. However, F(ab')2 fragments of the IVGG reacted only weakly with platelets, neutrophils, monocytes and lymphocytes. Binding of IVGG to platelets and neutrophils did not prevent opsonization of these cells by monoclonal antibodies with specificities corresponding to those previously ascribed to platelet and neutrophil autoantibodies. This suggests that IVGG does not act by blocking attachment of autoantibodies to platelets in ITP. PMID- 3107874 TI - The gene map of Homo sapiens: status and prospectus. PMID- 3107875 TI - Cloned factor VIII and the molecular genetics of hemophilia. PMID- 3107876 TI - Comparison of deficiency alleles of the beta-globin and factor VIII:C genes: new lessons from a giant gene. PMID- 3107877 TI - Fossil evidence on human origins and dispersal. PMID- 3107879 TI - Molecular genetic investigations of ancient human remains. PMID- 3107878 TI - Hominoid evolution based on the structures of immunoglobulin epsilon and alpha genes. PMID- 3107880 TI - Biochemical and biological properties of single-chain urokinase-type plasminogen activator. PMID- 3107882 TI - Lymphokines and monokines in anti-cancer therapy. PMID- 3107881 TI - Interleukin-2 and its receptor: structure and functional expression of the genes. PMID- 3107883 TI - Molecular basis of a human purine nucleoside phosphorylase deficiency. PMID- 3107884 TI - Molecular biology of Homo sapiens. PMID- 3107885 TI - Interleukin-2 receptor: structure, function, and expression. PMID- 3107886 TI - Chromosomal mapping of genes involved in growth control. PMID- 3107887 TI - Exploration of the cellular mediated immunity by the blastogenesis test during chronic brucellosis in human. AB - The diagnosis of the chronic, human brucellosis is frequently difficult and usually needs experimental methods. This paper describes a lymphocyte stimulation test with a Brucella antigen and the results of this test concerning 45 brucellic or not brucellic patients. It is concluded that this test is interesting, especially for the chronic and sero-negative Brucellosis diagnosis. PMID- 3107888 TI - Profiles of heterophile antibody to various mammalian erythrocytes in rural populations of Zambia. AB - Heterophile antibodies to sheep red blood cells (SRBC), rabbit red blood cells (RRBC), horse red blood cells (HRBC), murine (rat) red blood cells (MRBC) were investigated in a total of 416 serum samples from two rural areas of Zambia where major parasitic diseases are endemic. Distribution of antibody titers to RRBC were significantly different between the two study areas, whereas titers to SRBC were not significantly different. Sheep RBC's did not reveal a uniform consistent difference between the two communities with respect to schistosomiasis and malaria. Rabbit erythrocytes showed significant differences (P less than 0.05) between parasitologically positive and negative samples for schistosomiasis and malaria, respectively. No significant difference was observed between sexes, although females generally have a slightly higher titer for both SRBC and RRBC than males. No significant agglutinins were detected to HRBC and BRBC. Agglutinins to MRBC were generally too high to be of any differential value. It is suggested that sheep and rabbit erythrocytes might be useful probes for evidence of exposure to parasites and assessment of humoral immunologic status, albeit nonspecific. Further, it is inferred that the incidence of infectious mononucleosis in this region is rather low. A controlled investigation into the distribution of E-B viruses is suggested to explain absence of I-M-like agglutinins in a region climatically conductive to existence of arborviruses in general, and the E-B virus group in particular. PMID- 3107889 TI - Large scale isolation of RNA polymerase I of Tetrahymena pyriformis and the identification of polymerase-associated polypeptides. AB - A procedure has been developed for a large scale and rapid isolation of RNA polymerase I (EC 2.7.7.6) of Tetrahymena pyriformis. The enzyme is precipitated from the cell homogenate by Polymin P, extracted from the sediment and separated from RNA polymerase II by a treatment with phosphocellulose. The further purification procedure involves sedimentation in glycerol gradients and chromatography on heparin-Sepharose and DEAE-Sephadex. The last step achieved the separation of RNA polymerase I from RNA polymerase III. On the basis of different criteria RNA polymerase I is assumed to consist of two large subunits of 180 and 118 kDa and nine subunits smaller than 50 kDa. Additional polypeptides have been identified which are associated with RNA polymerase I but are not found in integral stoichiometric amounts. Except for certain minor differences RNA polymerase I purified from the cell homogenate shows the same structure as the enzyme obtained from isolated macronuclei (Mueller et al., 1985). PMID- 3107890 TI - Glutathione transferase activity during Bufo bufo development. AB - High levels of glutathione transferase activity were measured during the development of the embryos of Bufo bufo including unfertilized eggs. After stage 4 glutathione transferase activity gradually decreased until stage 25 when the minimum was reached. No change in the number of isozymes was noted during development according to isoelectric focusing analysis performed on the cytosolic fractions of selected stages. PMID- 3107891 TI - Neurofibromatosis: clinical and genetic features. PMID- 3107893 TI - The orthopaedic manifestations of neurofibromatosis. PMID- 3107892 TI - Neurological manifestations of neurofibromatosis. PMID- 3107894 TI - Hypertension and neurofibromatosis: secondary causes. PMID- 3107895 TI - Diagnostic imaging in neurofibromatosis. PMID- 3107896 TI - Neurofibromatosis: 1977-1987. PMID- 3107897 TI - New concern for an old disease. PMID- 3107898 TI - Anesthesia for combined heart and lung transplantation. PMID- 3107899 TI - Enteral nutrition. AB - The introduction of fine-bore tubes and other equipment for tube feeding and the appearance on the market of defined formula nutritional preparations have revolutionised the technique of enteral feeding making it cheap, effective and relatively free of complications when used correctly. Although primarily a clinical exercise, it relies very much on biochemical support, particularly in difficult cases. The clinical biochemist should therefore have a general understanding of this and other aspects of clinical nutrition if he is going to provide that support appropriately. PMID- 3107900 TI - Practical aspects of intravenous nutrition. PMID- 3107901 TI - Practical aspects of paediatric nutrition. PMID- 3107902 TI - Metabolism and its control. PMID- 3107903 TI - Digestion and absorption of carbohydrate protein and fat. PMID- 3107904 TI - Pharmacotherapy for recovery of function after brain injury. AB - Considerable attention has recently been focused on the development of pharmacotherapies for promotion of recovery of function after brain injury. This article reviews both animal and human experimentation in two areas which appear to have considerable clinical applicability in the very near future for promoting recovery: drug manipulation of neurotransmitter systems and administration of gangliosides. Since the most important problem after brain injury is restoration of lost behavioral capabilities, this is the central theme of this review. The possible mechanisms of the effects of these pharmacological agents are only discussed for treatments with demonstrated beneficial or harmful effects on behavioral recovery. An attempt is also made to indicate possible common mechanisms and the clinical potential of the various treatments; future directions for research are suggested. PMID- 3107905 TI - Control of morphogenesis in myxobacteria. AB - The myxobacteria are Gram-negative soil bacteria that live in large communities known as swarms. The most remarkable characteristic of myxobacteria is their ability to form fruiting bodies that have a species-specific shape and color. Fruiting body formation requires the concerted effort of hundreds of thousands of cells. Development is initiated only when two conditions are satisfied. The cells must be nutritionally deprived (environmental signal) and there must be many other cells in the vicinity (intercellular signal). The development of one species, Myxococcus xanthus, has been studied in the most detail. M. xanthus uses amino acids as its primary carbon, nitrogen, and energy source. Starvation for a single amino acid, or for inorganic phosphate, serves as the environmental signal. A variety of intercellular signals appear to control the initiation of development and the timing of subsequent developmental events. PMID- 3107907 TI - Identification of the specific phosphorylated serine in the bovine alpha crystallin A1 chain. AB - Previous work (1,2,3) has indicated that the in vivo post-translational modification of the alpha crystallin primary gene product A2 is due to a specific phosphorylation process involving a serine residue located in a chymotryptic fragment with the sequence ARG-LEU-PRO-SER-ASN-VAL-ASP-GLN-SER-ALA-LEU which corresponds to the residues 119 to 129 of the polypeptide chain. To define which of the two serines is phosphorylated, the present experiments were carried out. The 32P-labeled chymotryptic fragment was obtained from alpha crystallin isolated from the outer cortex of calf lenses incubated in the presence of [32P] orthophosphate. By analyses of the products obtained after Edman degradation, utilizing electrophoresis in cellulose TLC plates and radioautography, it was possible to locate the phosphate in the serine residue at position 122 in the polypeptide chain. No phosphate could be detected in the serine residue at position 127. PMID- 3107906 TI - Inhibition of aldose reductase from human retina. AB - Aldose reductase was prepared from a pool of 21 male and 16 female human retinas by ammonium sulphate fractionation (40-75% saturation) and chromatography on DEAE Sephacel and Matrex-OA. The overall purification was 132-fold with 50% recovery of enzyme activity. The concentrations of the aldose reductase inhibitors Sorbinil, Statil and M79175 required to give 50% inhibition (IC50 value) of enzyme activity with the model substrate 4-nitrobenzaldehyde (4NB) were 3.4 microM, 2.3 microM and 0.22 microM respectively. This indicated that M79175 was the most effective inhibitor tested of aldose reductase with 4NB in vitro. These inhibitors were more effective when tested against aldose reductase activity with glucose, the substrate which might play a role in the pathogenesis of diabetic complications. Sorbinil gave an IC50 (glucose) of 0.40 microM; M79175 and Statil were more effective. At an inhibitor concentration of 0.1 microM the % inhibitions observed were: Sorbinil 20% M79175 55%, Statil 76%. Thus Statil was the most potent compound tested against human retinal enzyme using the more physiological substrate in vitro. This report provides the first direct evidence that human retinal aldose reductase is susceptible to inhibition by compounds designed for chemotherapy of diabetic complications, and indicates that the concentrations of inhibitor required for a substantial block of activity in vitro are lower than those attained in plasma in man. PMID- 3107908 TI - Cytochrome P450, drug metabolizing enzymes and arachidonic acid metabolism in bovine ocular tissues. AB - Little information is available on drug metabolizing enzymes in ocular tissues. We investigated the presence of various cytochrome P450 isozymes by measuring different drug metabolizing enzymes, i.e., aryl hydrocarbon hydroxylase, 7 ethoxycoumarin-o-deethylase and benzphetamine demethylase activities in ciliary body, corneal epithelium and endothelium, retina and retinal pigment epithelium. Our results demonstrate that the ciliary body and the retinal pigment epithelium possess the highest activities of cytochrome P450-dependent monooxygenases in the eye. The highest activity of drug metabolizing enzymes is accompanied by high activity of NADPH cytochrome P450 (C) reductase, an integral component of this enzyme system. Heme oxygenase, a key enzyme for the regulation of heme availability to hemoproteins such as cytochrome P450 also demonstrate high activity in these two ocular tissues. Although the corneal epithelium has a lower activity of drug metabolizing enzymes, it possesses the highest activity of cytochrome P450 species capable of metabolizing arachidonic acid to biologically active compounds, whereas the other ocular tissues possess cyclooxygenase as the main microsomal enzyme that metabolizes arachidonic acid. Whether the observed catalytic activities of drug metabolizing enzymes seen in ocular tissues are associated with major or minor forms of cytochrome P450 is not yet know. However, the specialized location of cytochrome P450 isozymes in ocular tissues suggests a physiological function related to activation of endogenous compounds such as arachidonic acid, in addition to detoxification of drugs. PMID- 3107909 TI - Chondroitin 6-sulfate glycosaminoglycan is a major constituent of primate cone photoreceptor matrix sheaths. AB - Recent work suggests that chemically and structurally distinct domains of the interphotoreceptor matrix ("cone matrix sheaths") surround cone photoreceptor outer segments and ellipsoids. This specific regionalization of at least some molecular constituents of the interphotoreceptor matrix may establish a unique cone-associated microenvironment. Previous histochemical and biochemical investigations have shown that a variety of glycosaminoglycans are components of the interphotoreceptor matrix and that the structural integrity of cone sheaths is slightly disrupted by glycosaminoglycan-degrading enzymes. In order to pursue the possibility that specific glycosaminoglycan species establish cone matrix sheath domains, monoclonal antibodies directed against various unsaturated glycosaminoglycans have been screened on sections of primate retina. The results of these studies identify chondroitin 6-sulfate glycosaminoglycan as a specific component of primate cone matrix sheaths. PMID- 3107910 TI - Nature of the inflammatory process in the central nervous system of mice infected with lymphocytic choriomeningitis virus. PMID- 3107911 TI - Questioning the role of the embryonic bursa in the molecular differentiation of B lymphocytes. PMID- 3107912 TI - Immunoglobulin gene rearrangements in pre-B cells. PMID- 3107913 TI - Differentiation of murine B-cell progenitors in agar culture: determination of the developmental potential of clonable pre-B cells. PMID- 3107914 TI - Expression of the immunoglobulin heavy-chain variable gene repertoire. PMID- 3107915 TI - Programmed development of the antibody repertoire. PMID- 3107916 TI - Enhancement and attenuation of cytogenetic damage by vitamin C in cultured human lymphocytes exposed to thiotepa or L-ethionine. AB - Vitamin C (vit C) at 2 mM enhanced sister chromatid exchange (SCE) frequencies induced by Thiotepa (THIO) or L-ethionine (L-ETH) in cultured human lymphocytes. However, when vit C was tested at 0.02 mM and 0.2 mM a rather protective effect on SCE rates induced by THIO or L-ETH was identified. Vit C (2 mM) caused a cell division delay in cultures treated with THIO or L-ETH. Division delays caused by THIO or L-ETH were reversed in the presence of 0.02 mM or 0.2 mM vit C. Mitotic indices (MIs) in cultures treated with THIO or L-ETH continued to be suppressed in the presence of 2 mM vit C. However, vit C at 0.02 mM reversed suppression of MIs caused by L-ETH or THIO. These findings illustrate the complexity of the interactions of vit C in biological systems and indicate that with different concentrations vit C can cause or prevent genetic toxicity. PMID- 3107917 TI - Localization of the human catalase and apolipoprotein A-I genes to chromosome 11. AB - Studies of the catalase and apolipoprotein A-I genes are pertinent to the understanding of human disease. Not only are these genes involved in acatalasemia and atherosclerosis, respectively, but they are also important gene markers for chromosome 11, deletions of which are involved in the development of Wilms tumor. We have used in situ hybridization to localize these genes to specific bands on chromosome 11. Hybridization with a catalase cDNA yielded a significant number of cells (38%) exhibiting label at band 11p13. A high percentage of metaphase cells (50%) hybridized with a human genomic fragment containing the gene for apolipoprotein A-I displayed labeling at 11q13. PMID- 3107918 TI - The gene for human carbonic anhydrase II (CA2) is located at chromosome 8q22. AB - The gene CA2 for the human carbonic anhydrase II isozyme is encoded in band q22 of chromosome 8. These data and supporting evidence predict that the genes for carbonic anhydrase I and III are also physically closely linked in this chromosomal region. PMID- 3107919 TI - [Carbonic anhydrase activity in human saliva and the formation of deposits on the teeth]. PMID- 3107920 TI - Vasodilator therapy-induced pacemaker syndrome. AB - Disabling presyncopal attacks were provoked in a patient with a sinus nodal disorder and cardiac pacemaker by treatment with antianginal vasodilators. At cardiac catheterization a severe fall in aortic pressure was documented during ventricular pacing, when desynchronized atrial contractions coincided with ventricular systoles. After withdrawal of the medication, no obvious changes in arterial pressure were associated with ventricular pacing, and the patient became free of dizziness. Vasodilating drugs may provoke episodic hypotension with characteristic features of the pacemaker syndrome. PMID- 3107921 TI - Diurnal rhythm of asthma. AB - A diurnal rhythm in the occurrence and severity of asthma symptoms is almost universal with disturbed sleep due to enhanced symptoms at night paralleled by a change in lung function. The mechanisms involved are not completely understood. However, it appears to be related to an exaggerated response to a circadian rhythm in lung function observed in healthy individuals. The circadian nature of asthma must be considered in diagnosis and evaluating the adequacy of therapy. Inhaled therapy with additional suppressive and anti-inflammatory treatment as required should be effective in treating most patients with nocturnal asthma. PMID- 3107922 TI - Studies on intrahepatic hepatitis B virus DNA in 98 viral hepatitis B patients. PMID- 3107923 TI - Micro-wave: an alternative to electric heating in the treatment of chronic lymphedema of extremities. PMID- 3107924 TI - Fluorocarbon preservation of kidney transplants. PMID- 3107925 TI - Integrated approach to malaria control emphasizing reduction of man-mosquito contact. PMID- 3107926 TI - Systemic scleroderma: a clinical and immunological study. PMID- 3107927 TI - Clinical evaluation of cefoperazone. PMID- 3107929 TI - Mesangial IgA glomerulonephritis in Hong Kong. A clinical review. PMID- 3107928 TI - The serum and red cell folate levels in pregnant women in Beijing. PMID- 3107931 TI - Congenital hypertrichosis universalis associated with gingival hyperplasia and macromastia. PMID- 3107930 TI - Albendazole in nematode, cestode, trematode and protozoan (Giardia) infections. PMID- 3107932 TI - Comparative study on serum monoaminoxidase and EEG in nickel carbonyl workers. PMID- 3107933 TI - Studies on the habitat of Phlebotomus chinensis in Beijing suburbs. PMID- 3107934 TI - Diacetylchitin coated resin hemoperfusion in dog acute pentobarbital intoxication. PMID- 3107935 TI - Membrane-associated HPRTase activity in hyperuricemic and Lesch-Nyhan syndrome cells. PMID- 3107936 TI - Histopathological observation of phacolytic glaucoma. Report of 5 cases. PMID- 3107937 TI - [The Hickman catheter in bone marrow transplantation, long-term cytostatic and infusion therapy. Experience of 102 catheters in children]. AB - Right atrial Hickman catheters are used for long-term venous access in children suffering from leukemia and malignoma. Parenteral alimentation, blood withdrawal and bone marrow transplantation can be performed safely without high incidence of cutaneous infections and sepsis due to a long subcutaneous tunnel. Aseptic dressing changes and catheter care are the most important prerequisites for a low complication rate in the use of these catheters. Septicemia and technical complications observed following the use of 102 Hickman catheters in 81 children are reported and discussed. PMID- 3107938 TI - [DMBA-induced leukoplakia of the tongue in rats]. PMID- 3107939 TI - Discovery and partial characterization of primate motor-system toxins. AB - beta-N-Oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) are chemically related excitant amino acids isolated from the seed of Lathyrus sativus (BOAA) and Cycas circinalis (BMAA), consumption of which has been linked to lathyrism (an upper motor neuron disorder) and Guam amyotrophic lateral sclerosis (ALS), respectively. Both diseases are associated with degeneration of motor neurons. Experimentally, single doses of BOAA or BMAA induce seizures in neonatal mice and postsynaptic neuronal oedema and degeneration in explants of mouse spinal cord and frontal cortex. Preliminary studies show that these behavioural and pathological effects are differentially blocked by glutamate receptor antagonists. In macaques, several weeks of daily oral doses of BOAA produce clinical and electrophysiological signs of corticospinal dysfunction identical to those seen in comparably well-nourished animals receiving a fortified diet based on seed of Lathyrus sativus. By contrast, comparable oral dosing with BMAA precipitates tremor and weakness, bradykinesia and behavioural changes, with conduction deficits in the principal motor pathway. BOAA and BMAA (or a metabolite thereof) are the first members of the excitotoxin family to have been shown to possess chronic motor-system toxic potential. These observations provide a rational basis for searching for comparable endogenous neurotoxins in sporadic and inherited forms of human motor neuron disease. PMID- 3107940 TI - [Glutamate dehydrogenase determination in epilepsy]. PMID- 3107941 TI - [Smear-positive and culture-negative results in detecting acid-fast bacilli in the sputum and their clinical significance]. PMID- 3107942 TI - Bicentennial anniversary of the birth of J.E. Purkinje (1787-1987). PMID- 3107943 TI - Calcification of the driving diaphragm in a total artificial heart. AB - The implications of mineralization on the diaphragm of a TAH were highlighted. The problem was discussed from the point of view of time and site of calcifying deposit formation, and individual patterns of calcification as well as the question of the relationship between mineralization processes and thrombogenicity were considered. Attention was likewise given to actual calcification with regard to its mechanism, and to the risks that the calcification process in an artificial heart pose to the organism. Next, the options to prevent mineralization were reviewed. The issue as analysed especially on the basis of results obtained in the Centre of the State Research project called "Assistance and Replacement of the Heart", Regional Institute of National Health in Brno, Department of Pathological Physiology. It was pointed out that diaphragm calcification can compromise the life of an individual after many years of surviving with an artificial heart. Still, the risk is zero within the first two or three months following artificial heart implantation. The fact was underlined that the last model of a Czechoslovak-made artificial heart, called TNS Brno VII, re-designed in an effort to prevent the breaking away of calcified microemboli from the diaphragm, features optimal athrombogenity. Thus, the clinical version of this brand-new Czechoslovak TAH can be regarded as the best model of an artificial heart to be implanted as a life-saving measure tiding the patient over a period before a cardiac transplantation can be performed. PMID- 3107944 TI - Czechoslovak contribution to current concepts in impotence, its pathogenesis, diagnosis and treatment. AB - Czechoslovak contribution to the current concepts in impotence, its pathogenesis, diagnosis and treatment, consists especially in: the recognition of the haemodynamics of erection. The process involves two stages; in the first one, the arterial bed must deliver to the corpora cavernosa (CC) threshold values of volume and pressure needed for filling and distention of the CC, in the second period, the CC function as a closed system on the hydraulic principle, and contractions of the ischiocavernous muscles increase intracavernous pressure to suprasystolic values, the observation that it is just failure of the haemodynamics of erection that plays an important role in the pathogenesis of impotence in a majority of patients. The development of artificial erection into a real functional examination of the CC enables to differentiate: disorders with normal haemodynamics of erection, those due to insufficient arterial supply, insufficient blockage of venous return, or insufficient and ineffective contractions of the ischiocavernous muscles. the development of the phalloarteriographic technique which allows a precise anatomical diagnosis of the lesions in the afferent arterial bed, providing the basis for the development and indication of a number of reconstructive procedures in the arterial bed supplying the CC. In addition, the examination has also helped to clarify the relationship between erectile disorders, arterial disease and their risk factors. In retrospect, Czechoslovak research into impotence has substantially contributed to the recognition of vasculogenic impotence, to the therapy of arteriogenic erectile disorders and to a basic change in the concepts of the aetiology and pathogenesis of impotence. PMID- 3107946 TI - Regulation of iron uptake in erythroid and non-erythroid cells. AB - Iron uptake and the transferrin endocytotic cycle were studied in Friend erythroleukemia 707 cells cultured over a period of 5 days after induction with dimethylsulphoxide, or without it. The increase in iron uptake observed 5 days following induction with dimethylsulphoxide is not associated with a corresponding increase in the number of transferrin receptors. While the uptake rate of induced cells is 26 atoms of iron per one transferrin receptor per hour, in non-induced cells, the rate is only 15 atoms of iron. Induced cells retain all iron, with endocytosis and transferrin release occurring at the same rate. By contrast, the rate of iron release from non-induced cells is slower and part of the iron bound to transferrin returns from the cell. Haem inhibits iron uptake in induced cells and has no effect on non-induced cells. Its regulatory role is apparently confined to the erythroid cell with massive haemoglobin synthesis. The differences in the efficacy of iron release from induced and non-induced erythroleukemia cells are, possibly, apart from the changes in the number of transferrin receptors, an additional factor involved in the control of cellular iron uptake. PMID- 3107945 TI - Preparation and implementation of pancreas transplantation programme in diabetic patients. AB - Having reviewed the state-of-the art trends in pancreas transplantation over the world, the authors describe their own experimental studies preceding elaboration of the technique of pancreatic segment transplantation with duct obliteration. In their technique, the splenic artery is interposed in the course of the iliac arteries of the recipient. The procedure of the selection of diabetic patients suitable for a combined pancreas and kidney transplantation is presented. The results in 13 recipients with insulin-dependent diabetes and progressed organ complications are evaluated. In these patients a combined pancreas and kidney transplantation is of a better prognosis compared with the conventional treatment methods. PMID- 3107947 TI - Experience with orthotopic heart transplantation. AB - Improving results of heart transplantation have led to a substantial increase in the number of transplantations performed each year ever since the early 1980s. The paper offers a review of our own experience with orthotopic heart transplantation. In the period between January 1984 and October 1986, a total of 11 transplantations has been carried out. Two patients died in the early postoperative period, nine were discharged from the hospital. There were two deaths in the late postoperative period. The seven surviving patients are in a satisfactory condition. Experience gathered hitherto in the world, and confirmed by our own results, shows that heart transplantation has become a therapeutic modality in patients selected on the basis of stringent criteria. The procedure, however, must be performed only in centres having a sufficient body of experience in cardiology, cardiac surgery, and transplantation of other organs. PMID- 3107948 TI - Experimental parameters and a biological standard for acridine orange detection of drug-induced alterations in chromatin condensation. AB - We investigated a number of sample-preparative parameters for use of flow cytometry to detect chromatin condensation in cells stained with acridine orange after DNA in situ is partially denatured by acid treatment. Stability and data reproducibility for both control and drug-treated ME-180 and HT-29 cells were assessed over: a range of cell concentrations in 2.56 X 10(-5) M acridine orange; 15 days of storage in fixative; various times between RNase digestion and staining; and increasing times between staining and analysis. Listmode data for red and green fluorescence were collected and mean fluorescence intensities of G1, S, and G2 subpopulations of HT-29 and ME-180 cells were computed. These were normalized to data from HeLa-S3 cells and fluorescent microspheres to control for inter-experiment variations in staining and instrumental parameters, respectively. The normalized red and green fluorescence data were used to calculate alpha 1 for G1 cells [alpha t = red fluorescence/(total fluorescence)]. Exponentially growing HeLa-S3 cells were a very consistent and reproducible biological standard to control for fixation and staining variability. Mean fluorescence intensities of control and difluoromethylornithine-treated (i.e., polyamine depleted) cells remained stable and reproducible across all tested ranges for cell concentration, storage in fixative, and time after RNase digestion. This technique can thus be used to evaluate difluoromethylornithine induced changes in chromatin condensation of samples stored for as long as 2 weeks and analyzed all on 1 day. PMID- 3107949 TI - Simultaneous increased expression of E-rosette receptor (CD2, T11) and T cell growth factor receptor on human T lymphocytes during activation. AB - The E-rosette receptor (CD2, T11) is a differentiation antigen expressed on immature and mature human T lymphocytes. Activation of T cells from human peripheral blood with phytohemagglutinin (PHA) or with monoclonal antibody to the CD3-Ti complex (anti-Leu-4) caused the expression of CD2 to increase 10- to 20 fold. Dual parameter correlated analyses with antibody to the T cell growth factor (TCGF) receptor (anti-Tac) and anti-CD2 antibody demonstrated that the increase in CD2 expression occurred at the same time and on the same cells that expressed the TCGF receptor after stimulation with PHA. The increased expression of CD2 and the initial expression of Tac were totally inhibited by cycloheximide, but were not affected by sufficient actinomycin-D to block the T cell proliferative response. The expression of CD2 was compared with the expression of CD4 and CD8, i.e., T cell differentiation antigens on cytotoxic/suppressor or helper T cells, respectively. Although virtually all of the small percentage of freshly isolated Tac+ peripheral blood cells belonged to the CD4+, CD8- subset, both CD4+ and CD8+ T cells were equivalently activated by PHA to express Tac. By 20-30 hr after activation, the expression of CD4 or CD8 was initially decreased 10-50%. Subsequently, the expression of CD4 and CD8 returned to the levels on resting T cells but did not increase further. Therefore, the increase in CD2 expression does not reflect a universal property of cell surface antigens on activated T lymphocytes. PMID- 3107950 TI - Computers: buying the best. PMID- 3107952 TI - Planning the perfect practice. PMID- 3107953 TI - Good scheduling stops stress. PMID- 3107951 TI - Improve your interviewing skills. PMID- 3107954 TI - Partnerships: when the honeymoon is over. PMID- 3107955 TI - Computerized information management: is it cost-effective for diabetes care? PMID- 3107956 TI - [Carcinoma of esophagus treated by 8MV X-ray and checked by simulator]. AB - From January 1, 1978 to December 31, 1983, 570 patients with carcinoma of esophagus were treated by 8 MV X-ray and checked by the Philips simulator. In order to assess their value, a series of 3,798 patients reported previously was used for comparison. To further evaluate the effect of 8 MV X-ray and simulator separately, a series of 154 patients was treatment by non-8 MV X-ray during the same period. The results showed that the 1 and 3 year survival rates of 8 MV X ray series were better than the 3,798 series (P less than 0.01). It means that after the use of simulator and 8 MV X-ray the survival rates were improved. As compared to the radiation other than 8 MV X-ray, there was no difference between 8 MV X-ray and non-8 MV X-ray series, which means that the improvement may have been due to the better localization by the simulator. Having more importance, no radiation myelitis was found after the use of simulator. The sex, age, length, location, X-ray type, NSD and causes of failure were compared in these groups. PMID- 3107957 TI - [Reconstruction of the liver microsomal monooxygenase system in a solution from NADP-H-cytochrome P-450 reductase and cytochrome P-450 monomers]. PMID- 3107958 TI - The post-antimicrobial suppressive effect of quinolone agents. AB - A post-antimicrobial effect (PAE) was seen with all of the new 4-quinolones studied: ciprofloxacin, ofloxacin, Cl-934, Ro 23-6240, A-56619 and S-25930. The post-antimicrobial suppression of growth was for 4-8 h in the case of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa. PEA was demonstrated both in Mueller-Hinton broth at pH 7.4 and in urine at pH 5.5 with a Mg2+ concentration of 9.5 mM. Resistant organisms, with MICs greater than 4 micrograms/ml, showed a PAE after a 2-h exposure to 200 micrograms/ml of 4 quinolones. This demonstrates that PAE is seen for 4-quinolones even under conditions in which they are less active. PMID- 3107959 TI - A new trifluorinated quinolone: Ro 23-6240 (AM 833). AB - Ro 23-6240 is a new fluoroquinolone displaying pronounced activity against a wide range of Gram-positive and Gram-negative pathogens. In order to obtain information about the absorption, distribution and excretion of this quinolone in man, six healthy volunteers received in cross-over an intravenous infusion of 100 mg Ro 23-6240 and an oral dose of two tablets corresponding to 400 mg Ro 23-6240. Serial plasma and urine samples were assayed for unchanged substance by HPLC with subsequent fluorescence or UV detection. Pharmacokinetics were evaluated from these data assuming a two-compartment open model. Characteristic of this new antibacterial are the high plasma levels following oral administration (Cmax: 4.5 micrograms/ml) and the long elimination half-lives (8-12 h). Both these parameters are favourable kinetic prerequisites for a once-a-day dosage regimen. In addition, the volume of distribution at steady state clearly exceeds 1 l/kg and points to good tissue penetration. Total systemic clearance was 122 ml/min and total renal clearance reached 89 ml/min. Within 96 h, 60-70% of the administered dose was recovered from urine as unchanged drug. The absolute bioavailability (extent of absorption) of the tablet amounted to 96%, indicating a complete absorption of this galenic formulation. PMID- 3107960 TI - Should dihydroergotamine-heparin be used for prevention of postoperative thromboembolism? AB - The combination of heparin 5000 U and dihydroergotamine 0.5 mg (HDHE) was marketed in the U.S. in 1985 for prophylaxis of postoperative deep venous thrombosis (DVT). This article evaluates the efficacy, safety, and cost of HDHE for abdominal, pelvic, thoracic, and total hip surgical prophylaxis. Although several controlled trials comparing HDHE to minidose heparin (MDH) indicate superior efficacy of HDHE for nonorthopedic surgical procedures, others do not. Differences in study design and insufficient sample sizes may account for the dichotomy. In the U.S. Multicenter Trial, MDH was surprisingly ineffective for preventing radiofibrinogen uptake test-proven DVT. The apparent superiority of HDHE over MDH is therefore questionable. Ergot-related side effects have been minimized in all studies due to careful patient selection. In actual use, the potential for such side effects appears to be increased. Because twice-daily HDHE is no more effective, costs 4-11 times more, and may pose a greater risk than MDH, the authors do not recommend its use for general surgical prophylaxis. HDHE may prove to be useful in patients undergoing total hip replacement. PMID- 3107961 TI - Carbamazepine and erythroid arrest. AB - A patient who developed anemia with an isolated erythroid toxicity following chronic carbamazepine administration is reported. The anemia quickly resolved with discontinuation of this drug. Other hematologic toxicities of carbamazepine are well described; however, an isolated erythroid toxicity is unusual. In addition, the onset of this drug-induced toxicity developed later than is expected for carbamazepine-associated hematological toxicities. This case demonstrates the suddenness with which hematological toxicities can occur with carbamazepine, and affirms the need for regular monitoring of patients. Any significant decrease in the patient's hemoglobin or hematocrit level requires close monitoring for the sudden development of serious anemia. PMID- 3107962 TI - Comment: topical mupirocin. PMID- 3107964 TI - Experiments on the interaction between orofacial function and morphology. PMID- 3107963 TI - [Surgery in chronic pancreatitis. II. Late results following non-resection operations]. AB - Between 1966 and 1985, 994 patients with chronic pancreatitis were treated at a University Surgical Department, 346 by drainage or diversion procedure, 339 by resection and 309 conservatively. The most frequent non-resecting procedures were: pancreatic pseudocyst drainage in 146, biliary-digestive tract anastomosis in 80, gastro-enterostomy in 15, biliary-tract revision in 58 and pancreatic duct drainage in 7 patients. More than half the patients had previously been operated on at least once. Overall postoperative death rate was 6.6%. Of those operated on up to 1983, whose subsequent course was analysed retrospectively, 16% had died (mean observation period 4.6 years). As many as 29% of patients had further bouts of pancreatitis. Weight remained steady or increased in 82%, the number of those with diabetes increased by 6%. All but 12% remained free of pain postoperatively or had only minor and occasional symptoms. Alcohol abuse decreased markedly. If alcohol consumption remained moderate (less than 50 g daily), late mortality rate was definitely decreased. Drainage or diversion procedures and pancreas resection are not competitive but complementary methods in chronic pancreatitis. Imaging techniques have helped the trend towards more conservative management. PMID- 3107965 TI - [Typical recurrent disease behavior of NANB hepatitis. A computer-assisted analysis]. AB - 1013 ALAT-attacks--in addition to the frequent asymptomatic onset of the disease and the high tendency of chronicity a typical symptom of the non-A, non-B hepatitis--were statistically analysed on 333 patients (of these 216 with uniform parenteral source of infection). 52% of the patients showed a multiphasic course. The aim of the analysis was the exact mathematical description of the attack behaviour and the discovery of presumed regularities. The investigation of the periodicity of the attacks showed a maxima of spectral density corresponding to a 7-day-rhythm. The trend function of the ALAT-amplitudes in the time-course was assessed as an exponential function. Between mono- and multiphasic ALAT-courses no significant differences existed concerning the clinical picture (icteric- anicteric--subclinical), but as regards the late prognosis the multiphasic courses exhibited highly-significantly more transitions into chronic hepatitis. From the time-serial analysis of the attacks can be deduced for practical application that the reliable detection of non-A, non-B hepatitis cannot be guaranteed with weekly screenings. Screenings at 2-day-intervals which take into consideration the attack-behaviour and the ascertained time of incubation are recommended. PMID- 3107966 TI - Stimulation of growth hormone release in dwarf and normal chickens by thyrotrophin releasing hormone (TRH) or human pancreatic growth hormone releasing factor (hpGRF). AB - The effect of thyrotrophin releasing hormone (TRH) or human pancreatic growth hormone releasing factor (hpGRF) on growth hormone (GH) release was studied in both dwarf and normal Rhode Island Red chickens with a similar genotype except for a sex-linked dw gene. Both TRH (10 micrograms/kg) and hpGRF (20 micrograms/kg) injections stimulated plasma GH release within 15 min in young and adult chickens. The increase in GH release was higher in young cockerels than that in adult chickens. The age-related decline in the response to TRH stimulation was observed in both strains, while hpGRF was a still potent GH releaser in adult chickens. The maximal and long acting response was observed in young dwarf chickens, suggesting differences in GH pools releasable by TRH and GRF in the anterior pituitary gland. The pituitary gland was stimulated directly by perifusion with hpGRF (1 microgram/ml and 10 micrograms/ml) or TRH (1 microgram/ml). Repeated perifusion of GRF at 40 min intervals blunted further increase in GH release, but successive perifusion with TRH stimulated GH release. The results suggest the possibility that desensitization to the effects of hpGRF occurs in vitro and that the extent of response depends on the number of receptors for hpGRF or TRH and/or the amount of GH stored in the pituitary gland. PMID- 3107967 TI - Plasma disappearance half-time and metabolic clearance rate of exogenous human growth hormone-releasing hormone-(1-44)-NH2 in normal subjects. AB - By means of human growth hormone-releasing hormone (hGHRH)-RIA using an antiserum directed toward the C-terminal region of hGHRH-(1-44)-NH2, the plasma disappearance half-time and metabolic clearance rate (MCR) of immuoreactive hGHRH (IR-hGHRH) were examined in normal subjects after an iv bolus injection of synthetic hGHRH-(1-44)-NH2 (1 microgram/kg BW). The disappearance of IR-hGHRH from plasma was characterized by a biexponential decay curve, with initial distribution and subsequent metabolic t1/2 value of 5.0 +/- 1.0 and 29.6 +/- 5.4 min (mean +/- SE), respectively. The MCR of IR-hGHRH was 6.1 +/- 1.2 ml/min X kg. The volume of distribution of IR-hGHRH was 3.3 +/- 0.4 liters. The molecular size of the plasma IR-hGHRH was not different from that of hGHRH-(1-44)-NH2 for at least 90 min after the injection of hGHRH-(1-44)-NH2 when examined by gel filtration chromatography. This prolonged clearance of hGHRH from human plasma relative to that of other hypothalamic hormones may in part explain the sustained plasma GH rises after hGHRH injection in man. PMID- 3107968 TI - Regulation of muscle fructose 2, 6-bisphosphate levels by sulfonylureas. AB - We examined the effect of sulfonylureas on the level of fructose 2, 6 bisphosphate (F-2, 6-P2) in muscle using a mouse hindlimb flow-through perfusion system. The F-2, 6-P2 level in muscle was increased by adding glibenclamide or tolbutamide in a dose-dependent manner. The stimulatory potency of each drug on F 2, 6-P2 formation was parallel to its hypoglycemic potency. Sulfonylurea stimulation of muscle F-2, 6-P2 formation is thought to be an important extrapancreatic action improving the deranged carbohydrate metabolism in diabetics. PMID- 3107971 TI - Effects of irradiation on canine tracheal epithelium: a physiological and morphological correlate. AB - We delivered 20 Gy irradiation in one fraction to a 6 cm segment of trachea in 11 dogs. Tracheal mucous transport was studied before and whenever possible at weekly intervals after irradiation using a gamma camera system and 99m technetium labeled sulfur colloid. Ten of the eleven animals were sacrificed at three different time intervals (1-2, 15-16 and 30-34 weeks) post-irradiation, and the tracheal epithelium removed for studies using Ussing chambers followed by preparation for microscopic analysis. Mucous transport along the length of the trachea was normal before irradiation, but following irradiation it became abnormal in the irradiated zone. Compared to the epithelium from the cranial and caudal segments, the irradiated epithelium had similar bioelectric measurements (potential difference, short-circuit current and resistance) and mannitol permeability. Also, the changes in the bioelectric measurements following indomethacin (10(-6) M) and epinephrine (10(-6) M) used sequentially, were similar in both the control and irradiated tissues. Scanning electron microscopic analysis of the irradiated zone revealed patches of nonciliated epithelial cells among the ciliates. We conclude that irradiation caused a persistent replacement of ciliated cells with nonciliates throughout the entire study period and that this alteration impaired mucous transport but did not affect epithelial ion secretion or barrier function. PMID- 3107969 TI - 6-keto prostaglandin F1 alpha and thromboxane B2 in isolated, buffer-perfused lungs from monocrotaline pyrrole-treated rats. AB - Monocrotaline pyrrole (MCTP) causes pulmonary endothelial cell injury and pulmonary hypertension in rats. Damage to endothelial cells in culture has been associated with altered prostacyclin (PGI2) production; therefore, it was of interest to determine if MCTP affected pulmonary PGI2 production. Release of the stable metabolites of PGI2 and thromboxane A2, 6-keto prostaglandin F1 alpha (6 keto PGF1 alpha) and thromboxane B2 (TxB2), respectively, was examined in isolated, buffer-perfused lungs from MCTP-treated rats at times when elevated pulmonary arterial pressure is first observed (day 7) and when the pulmonary hypertensive state has existed for some time (day 14), 6-keto PGF1 alpha release was not affected by MCTP treatment 7 or 14 days after a single intravenous injection of MCTP. TxB2 release was also unaffected at day 7, however 14 days after treatment TxB2 release was greater in lungs from MCTP-treated rats compared to controls. The concentration of both 6-keto PGF1 alpha and TxB2 increased when arachidonic acid was infused into lungs from control or treated rats. These data indicate that MCTP treatment increases the release of TxB2 from isolated lungs at a time when pulmonary hypertension is well-established, but not during early development of pulmonary hypertension. PMID- 3107970 TI - Effects of oxygen, calcium ionophore, and arachidonic acid on prostaglandin production by monolayer cultures of mixed cells and endothelial cells from rat fetal lungs. AB - Prostaglandins (PGs) synthesized by fetal and neonatal lungs play pivotal roles in pulmonary physiology, especially during the transition from uterine to independent life. One regulator of prostaglandin synthesis at this time may be oxygen. We examined the effects of 1% O2, 21% O2 and 50% O2 in 5% CO2, balance N2 (PO2 values in medium = 30 +/- 4, 142 +/- 4, and 260 +/- 3 mm Hg, respectively), on prostaglandin production from monolayer cultures of mixed or endothelial cells prepared from day 20 gestation rat fetal lungs. Cells were untreated or stimulated to produce prostaglandins by the addition of the calcium ionophore, A23187 (10(-5) M), or the prostaglandin precursor, arachidonic acid (AA, 1 microgram/ml). Prostaglandins 6-keto F1 alpha (6KF, the hydrolysis metabolite of prostacyclin, PGI2), E2, F2 alpha and 13,14-dihydro-15-keto PGF2 alpha (FM, the enzymatic metabolite of PGF2 alpha) were measured by radioimmunoassay. The basal release of 6KF from mixed cells into serum-free medium was approximately 2 ng/10(6) cells/3 days. The levels of 6KF were 10-fold greater than those of the other prostaglandins. Basal endothelial cell release of 6 KF was 30 ng/10(6) cells/3 days, and this was 15- to 100-fold greater than that of the other prostaglandins measured. In mixed cells, oxygen treatment for 3 days had no effect upon the basal release of any prostaglandin, nor was there any effect of oxygen upon the basal 6KF or PGE2 production in endothelial cells. However, both PGF2 alpha and PGFM production by endothelial cells was decreased (p less than 0.05) in 50% O2 compared to 1% O2. Both A23187 and AA enhanced prostaglandin release from mixed and endothelial cells. Ionophore-stimulated 6KF net production in mixed cells was greater in 21% O2 than in 1% O2 (p less than 0.05). Calcium ionophore stimulated the net production of 6KF and PGE2 in endothelial cells in 21% O2 versus 1% O2 (p less than 0.05), and AA enhanced the net production of 6KF, PGE2 and PGF2 alpha in endothelial cells in 21% O2 versus 1% O2. We conclude that rat fetal pulmonary cells produce prostaglandins from endogenous and exogenous substrates, that prostaglandin production is sensitive to Ca2+ mobilizing agents, and that the production of the vasodilators PGI2 and PGE2 increases in the presence of 21% O2 and a stimulating factor. PMID- 3107972 TI - Effects of anticonvulsants on cell growth and enzymatic and receptor binding activity in a neuroblastoma x glioma hybrid cell culture. AB - The effects of anticonvulsants on markers of growth, intracellular enzymes, and synaptic functions were evaluated using a rapidly dividing cholinergic neuroblastoma x glioma hybrid cell-line (NG108-15). Cell cultures were exposed for 4 days to phenobarbital, phenytoin, carbamazepine, or valproic acid. Anticonvulsant concentrations added to the media were selected to produce free levels in the cell media that were equivalent to free levels in humans ranging from therapeutic to very toxic. Free levels of anticonvulsants in the toxic range affected cell number, protein content, and neurochemical markers. However, only valproic acid and phenytoin reduced cell growth at therapeutic free drug concentrations. Valproic acid was the only medication to act as a differentiating agent, significantly increasing the activity of choline acetyltransferase, beta galactosidase, and muscarinic cholinergic receptor binding. These results emphasize the importance of performing drug studies at appropriate free drug concentrations and suggest that valproic acid differs from other commonly prescribed anticonvulsants by having both a growth-suppressing and a differentiating effect. PMID- 3107973 TI - Acute effect of anticonvulsants on amygdaloid kindled seizures induced with low frequency stimulations. AB - Acute effects of several antiepileptic drugs on low-frequency amygdaloid-kindled seizures were assessed. The number of stimulating pulses required for the provocation of epileptic afterdischarge (pulse-number threshold, PNT) was used as an indicator for the seizure-generating threshold. The duration of epileptic afterdischarge (AD duration) was used as an indicator for the severity of the induced seizures. Phenytoin (PHT) and carbamazepine (CBZ) reduced AD duration more than did elevating PNT. Conversely, phenobarbital (PB) and diazepam (DZP) elevated PNT more than did reducing AD duration. Weak effects on the two indicators, valproic acid (VPA) and ethosuximide (ESM), were observed. Low frequency kindling may be a useful experimental model of epilepsy in drug assessments. PMID- 3107974 TI - The effect of chronic felbamate administration on anticonvulsant activity and hepatic drug-metabolizing enzymes in mice and rats. AB - The possibility of tolerance development from chronic administration of felbamate (FBM) was investigated in mice and rats. Chronic administration (15 days) of FBM (150 mg/kg i.p.) in mice had no significant effect on either intravenous pentylenetetrazol (PTZ) seizure threshold or hexobarbital sleep time; however, hexobarbital sleep time was significantly increased after a single dose. Chronic administration (5-7 days) of FBM (48 or 95 mg/kg orally) in rats also had no significant effect on either maximal electroshock seizure activity or hexobarbital sleep time. Chronic administration of FBM at 238 mg/kg slightly decreased anti-subcutaneous PTZ activity in chronically treated rats (one of eight protected) as compared with those receiving only a single dose (three of eight protected), but there was no significant change in hexobarbital sleep time. Chronic treatment of rats for 7 days with 48 mg/kg had no significant effect on any hepatic parameters. However, 95 or 238 mg/kg of FBM significantly increased p nitroanisole O-demethylase activity. It is concluded that the increased hexobarbital sleep time induced by an acute dose of FBM reflects the CNS depressant effect of the substance. The increased p-nitroanisole O-demethylase activity observed after chronic administration may be indicative of some liver microsomal induction. Overall, FBM in doses ranging from 48 to 238 mg/kg appears to have minimal potential for tolerance development. PMID- 3107975 TI - Effects of radiofrequency radiation and simultaneous exposure with mitomycin C on the frequency of sister chromatid exchanges in Chinese hamster ovary cells. AB - Chinese hamster ovary (CHO) cells were exposed for 2 hr with and without mitomycin C (MMC) (1 X 10(-8)M) to pulsed wave radiofrequency radiation (RFR) at 2450 MHz. The repetition rate of 25,000 pulses per sec (pps), pulse width of 10 microseconds, and exposure geometry used, resulted in a specific absorption rate (SAR) of 33.8 W/kg. The following exposure regimens were used: a 37 degrees C water bath control; a water bath temperature control (TC) in which the continuously monitored medium temperature closely followed the temperature rise in the RFR-exposed flasks; and the RFR-exposed cells in a water bath set at 37 degrees C prior to exposure. RFR exposure resulted in a maximum cell culture medium temperature of 39.2 degrees C. In the absence of MMC, there was no significant increase in sister chromatid exchange (SCE) in the RFR-exposed or TC groups over that of the 37 degrees C control. When a simultaneous treatment of RFR and MMC occurred there was no statistical difference in SCE frequency from that caused by chemical treatment alone. PMID- 3107976 TI - Evaluation of aflatoxin B1 mutagenesis: addition of glutathione and glutathione-S transferase to the Salmonella mutagenicity assay. AB - The effects of glutathione (GSH) and the combination of GSH and glutathione-S transferase (GST) on aflatoxin B1 (AFB1) mutagenesis in the Salmonella mutagenicity assay using Salmonella typhimurium strains TA98 and TA100 were tested. Ten concentrations of AFB1 (0-1.0 micrograms/plate) were added to a liver microsomal homogenate (S9 mix) or to S9 mix containing GSH or S9 mix containing the combination of GSH + GST. One-third of the samples were plated directly. Two thirds were incubated for 30 min at 37 degrees C prior to plating, and of those, half included bacteria. All samples were plated according to Ames et al [1975]. The results show that the addition of GSH and GSH + GST affected AFB1 mutagenesis by forming the AFB1-GSH conjugate and decreasing the availability of AFB1-8,9 epoxide. The effect of GST on GSH activity varied with the strain because of the different amounts of S9 mix used. The formation of the AFB1-GSH conjugate was verified by using reverse-phase high-performance liquid chromatography for quantitation of AFB1 and detection of AFB1-GSH. PMID- 3107977 TI - Studies on the toxicity of cypermethrin and fenvalerate in different strains of Drosophila melanogaster Meig. (Insecta, Diptera). AB - To improve our knowledge of pyrethroid toxicity mechanisms, Drosophila melanogaster was chosen as a model species, with well-defined characteristics. This study reports the results of the toxic effects of cypermethrin and fenvalerate on larvae and adults of four D. melanogaster strains. Our results show that cypermethrin is more toxic than fenvalerate at larval and adult stages, that growth on media containing insecticide significantly decreases the rate of preimaginal development, and that adult males are more sensitive than are females to both insecticides. PMID- 3107978 TI - Effect of sugar mill effluent on oxygen uptake and carbon dioxide output of rice (Oryza sativa L.c.v. Mushoori) seedlings. AB - The effects of a sugar mill effluent on respiration of rice (Oryza sativa L.c.v. Mushoori) seedlings have been investigated. Each experiment consisted of two parts, the effect of various concentrations of the effluent and the time dependent changes induced by the undiluted effluent. A marked increase in the rate of respiration was noticed upon treatment with various concentrations of the effluent. The time-dependent changes in the respiratory rate were about threefold with the 12 hr of treatment, and thereafter a rapid loss was noticed. Additionally, the respiratory quotient was studied to elucidate the nature of the metabolism of seedlings as influenced by the effluent. PMID- 3107979 TI - Organization of the murine Ig-related lambda 5 gene transcribed selectively in pre-B lymphocytes. AB - lambda 5 is an immunoglobulin lambda light chain-related gene which is selectively transcribed in murine pre-B lymphocytes to yield a 1.2 kb poly(A)+ mRNA. Comparison of the nucleotide sequence of a 1 kb cDNA clone with the sequence of a genomic clone isolated from 70Z/3 murine pre-B lymphoma cells shows lambda 5 is composed of three exons spanning a 3.75 kb DNA segment. Conserved splice signal sequences at all exon/intron boundaries and the presence of a long open reading frame indicate that a functional mRNA molecule can be made. Exon I contains a cap-site and a potential ATG start codon as well as sequences encoding a signal peptide. This gene could encode a lambda 5 protein of 209 amino acids which has, however, not yet been identified. The 3' portion of exon II and all of exon III shows strong sequence homologies to J lambda L and C lambda L exons. Homology to the lambda L chain genes is lost in the 5' portion of exon II and throughout exon I. In exon I short homologies to leader sequences and to VH framework 1 sequences are seen. PMID- 3107980 TI - cDNA sequence for human bcr, the gene that translocates to the abl oncogene in chronic myeloid leukaemia. AB - The hallmark of human chronic myeloid leukaemia is a 9;22 chromosome translocation that fuses most of the c-abl oncogene to the 5' portion of the breakpoint cluster region (bcr) gene, such that a hybrid bcr-abl mRNA and polypeptide are generated. To clarify further the nature of this translocation, we have analysed the structure of normal human bcr mRNA by isolating large cDNA clones that collectively span the entire coding region and extend 2.6 kb upstream of those previously described. The 3150-bp nucleotide sequence reported here includes 534 bp of a GC-rich 5' non-coding segment and indicates, in conjunction with published sequences, that the bcr polypeptide comprises 1271 amino acid residues. The predicted polypeptide is unrelated to serine or tyrosine kinases, or indeed to any previously published sequence; its structure provides no evidence of a transmembrane region. Since probes from throughout the 4.8-kb cloned region hybridized to both the 4.5 and 6.7 kb normal bcr transcripts, both RNAs contain most or all of that region. PMID- 3107981 TI - Analyses of chicken immunoglobulin light chain cDNA clones indicate a few germline V lambda genes and allotypes of the C lambda locus. AB - cDNA libraries of chicken spleen and Harder gland (a gland enriched with immunocytes) constructed in pBR322 were screened by differential hybridization and by mRNA hybrid-selected translation. Eleven L-chain cDNA clones were identified from which VL probes were prepared and each was annealed with kidney DNA restriction digests. All VL probes revealed the same set of bands, corresponding to about 15 germline VL genes of one subgroup. The nucleotide sequences of six VL clones showed greater than or equal to 85% homology, and the predicted amino acid sequences were identical or nearly identical to the major N terminal sequence of L-chains in chicken serum. These findings, and the fact that the VL clones were randomly selected from normal lymphoid tissues, strongly indicate that the bulk of chicken L-chains is encoded by a few germline VL genes, probably much less than 15 since many of the VL genes are known to be pseudogenes. Therefore, it is likely that somatic mechanisms operating prior to specific triggering by antigen play a major role in the generation of antibody diversity in chicken. Analysis of the constant region locus (sequencing of CL gene and cDNAs) demonstrate a single CL isotype and suggest the presence of CL allotypes. PMID- 3107982 TI - Molecular analysis of the locus elav in Drosophila melanogaster: a gene whose embryonic expression is neural specific. AB - The embryonic lethal abnormal visual system (elav) locus in Drosophila melanogaster, a vital gene mapping within the 1B5-1B9 region of the X-chromosome has been cloned and analysed. Previous developmental analyses have shown that in addition to the embryonic requirement there is a post-embryonic requirement for elav function in the cells of the visual system. A DNA segment containing elav+ function was defined through germ line transformation experiments. This region encodes three embryonic poly(A)+ RNAs and two adult transcripts which are preferentially expressed in the head. In situ hybridization experiments clearly demonstrate that the embryonic expression of elav is restricted to the nervous system. PMID- 3107983 TI - Structure and nucleotide sequence of a Drosophila melanogaster protein kinase C gene. AB - Genomic and cDNA clones encoding a Drosophila melanogaster protein kinase C (PKC) homologue were identified using a bovine PKC cDNA probe. The cDNA clones contain a single open reading frame that encodes a 639 amino acid, 75-kd protein having extensive homology with bovine, human and rat PKC and homology with the kinase domains of other serine, threonine and tyrosine kinases. The Drosophila PKC gene is localized to region 53E of chromosome 2. The gene spans approximately 20 kb and contains at least 14 exons. Messenger RNA for PKC could not be detected in 0 3 h Drosophila embryos. Adult flies contain three PKC transcripts of 4.3, 4.0 and 2.4 kb. PMID- 3107984 TI - Catalysis in the crystal: synchrotron radiation studies with glycogen phosphorylase b. AB - Direct observation of the progress of a catalysed reaction in crystals of glycogen phosphorylase b has been made possible through fast crystallographic data collection achieved at the Synchrotron Radiation source at Daresbury, UK. In the best experiments, data to 2.7 A resolution (some 108,300 measurements; 21,200 unique reflections) were measured in 25 min. In a series of time-resolved studies in which the control properties of the enzyme were exploited in order to slow down the reaction, the conversion of heptenitol to heptulose-2-phosphate, the phosphorylysis of maltoheptaose to yield glucose-1-phosphate and the oligosaccharide synthesis reaction involving maltotriose and glucose-1-phosphate have been monitored in the crystal. Changes in electron density in the difference Fourier maps are observed as the reaction proceeds not only at the catalytic site but also the allosteric and glycogen storage sites. Phosphorylase b is present in the crystals in the T state and under these conditions exhibits low affinity for both phosphate and oligosaccharide substrates. There are pronounced conformational changes associated with the formation and binding of the high affinity dead-end product, heptulose-2-phosphate, which show that movement of an arginine residue, Arg 569, is critical for formation of the substrate-phosphate recognition site. The results are discussed with reference to proposals for the enzymic mechanism of phosphorylase. The feasibility for time-resolved studies on other systems and recent advances in this area utilizing Laue diffraction are also discussed. PMID- 3107985 TI - Superinduction of the human gene encoding immune interferon. AB - Mitogen-induced interferon-gamma (IFN-gamma) gene expression was analyzed in human tonsil cells by titration of IFN-gamma activity and by quantitation of IFN gamma mRNA. Expression of the IFN-gamma gene can be superinduced extensively by two distinct methods: exposure to various inhibitors of translation, or to low doses of gamma-irradiation. gamma-Irradiated cells produce, after exposure to cycloheximide, up to 12-fold greater amounts of IFN-gamma activity. Within as little as 4 h after the addition of translation inhibitors, IFN-gamma mRNA levels rise 3- to 5-fold. Superinduction acts to increase the size of the wave of IFN gamma mRNA. Primary transcription of the IFN-gamma gene does not increase in cells superinduced by cycloheximide, nor can superinduction be explained by stabilization of IFN-gamma mRNA sequences. These findings show that, during normal induction, a labile protein acts post-transcriptionally to repress the accumulation of mature IFN-gamma mRNA sequences. The superinductive effects of cycloheximide and gamma-irradiation on levels of IFN-gamma are additive, suggesting that they affect different aspects of IFN-gamma gene expression. Superinduction by gamma-irradiation also has a post-transcriptional basis and is consistent with the possibility that expression of the IFN-gamma gene is normally controlled by the action of suppressor T cells. Even though the genes for human IFN-gamma and for interleukin-2 are both superinducible, a striking difference in the regulation of expression of these lymphokine genes is observed. Superinduction of IFN-gamma mRNA is not due to superinduction of interleukin-2. PMID- 3107988 TI - Class 1B agents lidocaine, mexiletine, tocainide, phenytoin. PMID- 3107987 TI - Electrophysiologic and clinical effects of intravenous and oral encainide in patients with Wolff-Parkinson-White syndrome and paroxysmal atrial fibrillation. AB - The electrophysiologic effects of encainide were studied in 10 patients with Wolff-Parkinson-White syndrome after intravenous (1 mg kg-1 in 60 minutes) and oral administration of two dose regimens (75 and 150 mg daily). Under control conditions atrial fibrillation (AF) with a rapid ventricular response was induced in all patients and atrioventricular reciprocating tachycardia (AVRT) in 9 patients. After intravenous encainide AF was no longer induced in 3/9 patients; in 3 of the remaining the accessory pathway (AP) was totally blocked and in the others the shortest RR interval increased from 213 +/- 6 to 297 +/- 91 ms and the mean RR interval from 293 +/- 39 to 362 +/- 79 ms. The lower dose of oral encainide prolonged the shortest RR interval from 206 +/- 24 to 273 +/- 64 ms and the mean RR interval from 280 +/- 48 to 368 +/- 52 ms in 6 patients; in 2 cases no preexcited beats were recorded and in 1 AF was not inducible. After the higher dose of oral encainide AF was still inducible in 7/8 cases; in 3 the AP was blocked and in the others the shortest and mean RR intervals increased from 202 +/- 30 to 280 +/- 24 ms and from 276 +/- 59 to 436 +/- 80 ms, respectively. After intravenous encainide antegrade conduction over the AP was blocked in 4/9 patients and the antegrade effective refractory period (ERP) was prolonged in another 4. Oral encainide blocked AP conduction in 4 cases and prolonged ERP considerably in the others.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107986 TI - EGF homologous sequences encoded in the genome of Drosophila melanogaster, and their relation to neurogenic genes. AB - The function of the neurogenic genes of Drosophila melanogaster is required for a normal pattern of commitment of neural and epidermal progenitor cells. In the course of searching for a molecular basis for the functional interrelationships that exist between the neurogenic genes, fragments of cloned DNA from the genes master mind (mam), Delta (Dl), Enhancer of split [E(spl)] and Notch (N) were hybridized to each other. Strong cross-hybridization was observed between a fragment of the Dl gene and a fragment of the N gene encoding a peptide with homology to several proteins of mammals, including the epidermal growth factor (EGF). Sequencing of this Dl fragment revealed an open reading frame encoding four EGF-like repeats with homology to the repeats found in the N gene. Screening genomic and cDNA libraries under conditions of reduced stringency with Dl and N probes that encode EGF-like repeats uncovered several cross-hybridizing clones, suggesting that other Drosophila genes may also encode such peptides. Part of a cross-hybridizing cDNA clone, derived from a gene located at position 95F on the third chromosome, was sequenced and found to encode five repeats with homology to those encoded by N and Dl. Preliminary evidence on the spatial pattern of transcription indicates that the gene at position 95F is regulated in its expression, as it is transcribed in all ectodermal derivatives, with the exception of the central nervous system. Indirect evidence suggests that this clone may derive from the crumbs (crb) gene, which is likely to be an hitherto unknown neurogenic gene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107989 TI - Flecainide and encainide. AB - Flecainide and encainide (class IC) are presently under clinical evaluation in Italy. They prolong the duration of the QRS but not the period of ventricular repolarisation: the prolongation of QT is due solely to the prolongation of the Q J. Flecainide and encainide are extremely powerful and are suitable for the treatment of reciprocating supraventricular paroxysmal tachycardia and of persistent reciprocating tachycardia, the prophylaxis of WPW atrial fibrillation including cases with a short anterograde refractory period of the anomalous pathway and the treatment of ventricular ectopic beats and ventricular tachycardia. Both drugs are probably effective for the treatment of atrial fibrillation. However, in the case of atrial flutter they are of little effect of sinus rhythm cardioversion; on the other hand they significantly prolong the duration of the A-A interval, with variable results on ventricular rate. Flecainide and encainide have 'parodoxical' arrhythmogenic effects, related to administration dosages, severity of the arrhythmia and seriousness of cardiopathy. Encainide shows peculiar pharmacokinetics due to hepatic oxidating metabolisation and to production of metabolites; among these the O demethylencainide and the 3-methoxy-O-demethylencainide have an antiarrhythmic activity, which is probably more important than the encainide parent and is longer-lasting. There are 'extensive', 'poor' and 'non-metaboliser' subjects. This results in wide pharmacokinetic inter- and intraindividual variability which must be taken into account during clinical treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3107990 TI - Studies on diphosphonate kinetics. Part I: Evaluation of plasma elimination curves during 24 h. AB - To improve the understanding of diphosphonate affinity to metabolically active bone, the underlying diphosphonate kinetics have been evaluated and compared to Cr-EDTA kinetics. MDP binds to plasma proteins, varying from 25% initially to approximately 70% after 24 h. The renal clearance of diphosphonate is found to be equal to Cr-EDTA clearance. Using simultaneous bolus injection of 99Tc-MDP and 51Cr-EDTA, it has been possible to obtain a coarse estimate of bone uptake of MDP. This uptake is found to correlate well with s-alkaline phosphatase, but since MDP binding to bone is reversible, the plasma elimination curve is not monoexponential. Therefore it has not been possible to describe the uptake of MDP in bone mathematically. PMID- 3107991 TI - Studies on diphosphonate kinetics. Part II: Whole body bone uptake rate during constant infusion--a refined index of bone metabolism. AB - To elaborate the understanding of diphosphonate kinetics, a non compartmental analysis is introduced. Using continuous infusion of 99mTc-methylene diphosphonate (Tc-MDP) and 51Cr-EDTA, as a cotracer, the diphosphonate clearance to bone (BDC) can be calculated. BDC is found to correlate well with the 24 h whole body retention of diphosphonate (WBR) (r = 0.89, P less than 0.01) when renal function is normal, but not in cases of reduced 51Cr-EDTA clearance. These findings indicate that BDC measurements are superior to the WBR technique in the estimation of bone turnover, especially when renal function is reduced. The BDC measurements may also constitute a useful tool for studies of diphosphonate uptake in bone, the foundation of bone scintigraphy. PMID- 3107993 TI - Inhibitory effect of intravenous lysine infusion on urea cycle metabolism. AB - Intravenous infusion of 0.5 mmol/kg L-lysine monohydrochloride was performed in six normal volunteer subjects aged 10-14 years to study the inhibitory effect of lysine on urea cycle metabolism. The lysine infusion resulted in a significant increase in plasma levels of arginine and ornithine, and in urinary homocitrulline, putrescine, and orotic acid, accompanied by a significant increase in blood ammonia. There was little change in plasma urea and citrulline. The increase in plasma arginine appears to reflect an inhibited arginase activity although the plasma urea level did not change. The increased homocitrulline excretion suggests that ornithine conversion to citrulline via ornithine transcarbamylase (OTC) was inhibited. The simultaneous increase in plasma ornithine and urinary putrescine may reflect an inhibition of mitochondrial ornithine transport. In addition to the direct ammoniagenic property of lysine, impaired ornithine conversion to citrulline resulting from the inhibition of both OTC activity and mitochondrial ornithine uptake by lysine may be responsible for the increase in blood ammonia and urinary orotic acid. Despite the retarded citrulline formation, a promoted efflux of citrulline from mitochondria may have kept the plasma citrulline level unchanged. PMID- 3107992 TI - Mechanisms of anticonvulsant drug action. I. Drugs primarily used for generalized tonic-clonic and partial epilepsies. AB - The mechanisms by which the clinically effective anticonvulsant drugs act include effects on neurotransmitter action, effects on repetitive neuronal firing mechanisms, effects on neuronal networks, and effects on neuronal ionic transport. The combination of effects possessed by each individual agent along with its pharmacokinetic properties determine the usefulness of each agent. Phenytoin, carbamazepine and phenobarbital are effective in generalized tonic clonic and partial epilepsies. Phenytoin exerts important effects on neuronal sodium and calcium ion transport, reduces repetitive firing, reduces excitation in neuronal networks of the brainstem reticular formation, and produces some decrease in the effect of the inhibitory transmitter, gamma-aminobutyric acid (GABA). Carbamazepine blocks repetitive firing mechanisms, reduces excitation in neuronal networks with some effect on sodium and potassium ion transport, and has effects on the actions of norepinephrine, adenosine and perhaps acetylcholine. Phenobarbital enhances the action of GABA with some reduction of repetitive firing and reduces excitation in reticular formation neuronal networks. PMID- 3107995 TI - Valproate increases cerebrospinal fluid glutamine levels. PMID- 3107996 TI - Neural circuits involved in parkinsonian motor disturbance studied in monkeys. AB - The outline of neurophysiological studies on a parkinsonian model in monkeys with mesencephalic ventromedial tegmental lesions was presented. By radiologically and physiologically controlled, selective deep-seated lesions, rigidity with or without tremor could be produced separately. From the results obtained mainly by microrecording from various levels of the brain, a neural circuit involved in production of rigidity and tremor has been proposed. PMID- 3107994 TI - Mechanisms of anticonvulsant drug action. II. Drugs primarily used for absence epilepsy. AB - The usefulness of the anticonvulsant drugs is determined by the mechanisms by which the agent acts and its pharmacokinetics. The general mechanisms of action of these agents include (1) effects on neurotransmitter action, (2) effects on repetitive neuronal firing mechanisms, (3) effects on neuronal networks, and (4) effects on neuronal ionic transport. Ethosuximide, valproic acid and clonazepam are used primarily in absence epilepsy. Valproic acid is also effective against generalized tonic-clonic epilepsy. Diazepam is used primarily in status epilepticus. Valproic acid enhances gamma aminobutyric acid (GABA)-mediated inhibition, reduces repetitive firing, and reduces both inhibition and excitation in neuronal networks. Clonazepam and diazepam enhance the inhibitory action of GABA, decrease inhibition in neuronal networks and affect calcium ion transport with lesser effects on repetitive firing. Ethosuximide reduces inhibition in neuronal networks, may interact with dopamine, and possibly affects sodium and potassium ion transport. Further work is needed to assess the degree of involvement of these effects in the anticonvulsant action versus the adverse effects of these agents. PMID- 3107998 TI - Adherence of gram-negative uropathogens to human uroepithelial cells. AB - The ability of bacteria to adhere to the mucosal surface is generally regarded as an important factor in infection. In particular, most urinary tract pathogens reach the kidney from the bladder. The attachment to the mucosa may promote colonization of the ureters and penetration of the renal pelvis by ascending infection. We have examined 50 patients with urinary tract infection and the uropathogens isolated from their urines were tested for adhesion to epithelial cells from fresh morning urine of healthy women. The results confirm that adherence of the microorganisms to uroepithelial cells is important for the establishment of infections of the upper urinary tract. PMID- 3107997 TI - A biochemical basis for psychotic symptoms in patients with brain dysfunction. AB - Thirteen brain dysfunctional patients with psychosis were compared to 11 brain dysfunctional patients without psychosis by EEG, CT scan and neuropsychological test abnormalities, and abnormalities in serine metabolism. None of the tests of conventional measures of brain pathology and pathophysiology significantly differentiated between the psychotic and nonpsychotic patients; only the last measure which has previously been shown to be a biochemical vulnerability factor for psychosis, was significantly different in the two groups. This study suggests that the brain pathology and pathophysiology per se are not significant factors that make such patients psychotic, but these patients are vulnerable to psychosis because of a biochemical abnormality. PMID- 3107999 TI - Radionuclide tests for the assessment of intestinal permeability. AB - 14C labelled-D-mannitol and aquo (ethylene-diaminetriacetoacetic acid) 51chromium (III) (51Cr EDTA) have been evaluated as markers of intestinal permeability in twenty-four healthy control subjects, sixteen patients with recently diagnosed coeliac disease and twenty subjects with coeliac disease in remission on a gluten free diet. The percentage excretion of 14C mannitol in urine collected for 6 h was significantly less in patients with coeliac disease (mean 6.7%) than controls (mean 13.5%). Conversely the excretion of 51Cr EDTA was significantly greater in patients with coeliac disease (mean 1.23%) compared with controls (mean 0.28%). The mean ratio of the percentage excretion of 51Cr to the percentage excretion of 14C was 0.29 in patients with untreated coeliac disease compared with 0.023 for healthy control subjects (P less than 0.001). Patients with untreated coeliac disease were clearly separated from control subjects by use of the 51Cr EDTA: 14C mannitol ratio but not by the excretion of independent markers. PMID- 3108001 TI - Metabolic consequences of differing protein diets in experimental renal disease. AB - Investigation into the effects of two different dietary proteins, casein and soya, fed at isonitrogenous and isocaloric levels, upon renal function, plasma amino acids and serum lipids, in normal and subtotally nephrectomized rats was undertaken. Groups 1 (24% casein, n = 10) and 2 (24% soya, n = 10) were maintained upon the diets for a 10-week period following subtotal nephrectomy, whilst groups 3 (24% casein, n = 6) and 4 (24% soya, n = 5) served as normal controls. Determination of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and histological analysis were undertaken at the end of the study. Serum lipids and plasma amino acids were determined in subtotally nephrectomized rats (group 5, 24% casein, n = 11: group 6, 24% soya, n = 12) 12 weeks following reduction in renal mass, and serum lipids determined in normal control animals (group 7, 24% casein, n = 10: group 8, 24% soya, n = 10). The glomerular filtration rate and ERPF in normal animals fed casein were significantly greater than those fed soya (P less than 0.01). Survival, proteinuria, renal histological damage and blood urea when killed were all significantly worse in subtotally nephrectomized animals fed casein. Serum cholesterol of groups 5 and 7 fed casein were significantly higher than groups 6 and 8 (P less than 0.05), whilst a significant reduction in serum triglyceride was found for group 6 (P less than 0.001). Plasma amino acids, and essential amino acid ratios of subtotally nephrectomized rats were equivalent, with the exception of plasma glycine (P less than 0.05). PMID- 3108000 TI - Altered interaction between triiodothyronine and its nuclear receptors in absence of cortisol: a proposed mechanism for increased thyrotropin secretion in corticosteroid deficiency states. AB - Thyroid hormones occasionally appear less effective when administered alone to patients with panhypopituitarism, and manifestations suggestive of hypothyroidism have been reported in patients suffering from untreated Addison's disease. In the latter condition, thyrotropin secretion is increased: this occurs already after as little as 2 days of temporary withdrawal of therapy with substitution doses of corticosteroids while circulating levels of thyroid hormones remain within normal limits. Therefore, a possible role of cortisol in interaction between triiodothyronine and its nuclear receptors was examined at the level of circulating lymphocytes obtained from patients with primary or secondary adrenocortical failure. The affinity of these receptors was found to be decreased, by more than 50% on average, in the absence of cortisol treatments. This change was promptly corrected upon resumption of therapy. The number of binding sites was not significantly modified. The influence of cortisol on thyroid hormone receptors discussed here might account for the clinical observations mentioned above. PMID- 3108002 TI - Pathogenesis of clinical hyponatremia: observations of vasopressin and fluid intake in 100 hyponatremic medical patients. AB - The pathogenesis of hyponatremia remains debated; therefore, we determined the roles of plasma vasopressin, fluid intake and renal free water excretion in hyponatremic medical patients. We evaluated 100 consecutive hypo-osmolar hyponatremic patients (PNa = 127 +/- 0.7 mM l-1) in a prospective manner. We observed: hyponatremia was often found in association with advanced congestive cardiac failure (twenty-five of 100 patients), liver cirrhosis (16%) and primary volume contraction (29%). There was a 17% in-hospital mortality of hyponatremic patients. This was primarily related to the severity of underlying illnesses rather than to hyponatremia per se. The most consistently observed laboratory finding of hyponatremia was non-osmotic vasopressin stimulation; mean observed PADH was 4.7 +/- 0.7 pg ml-1 and vasopressin was detectable by radioimmunoassay (RIA) in 91% of all patients. In addition to vasopressin stimulation we also found evidence of advanced 'circulatory underfilling' in most hyponatremic patients. Mean urinary osmolality was hypertonic to plasma (441 +/- 17.4 m0sm kg H2O-1). This applied to patients with hyponatremic cardiac failure, liver cirrhosis and volume contraction. Almost all of these patients received high ceiling diuretics. (v) Spontaneous mean daily fluid intake was 2.4 +/- 0.2 l. In summary, our findings suggest that disturbances of vasopressin, fluid intake and renal free water excretion co-operate in the pathogenesis of hyponatremia. In clinical states of advanced circulatory underfilling the occurrence of hyponatremia indicates a poor prognosis of the patient. PMID- 3108003 TI - Amino acid metabolism during the anabolic phase of severely burned patients: with special reference to sulphur amino acids. AB - Owing to the high content of cyst(e)ine and sulphated mucopolysaccharides in skin tissues, an increased demand for sulphur amino acids could be expected during the anabolic phase in severely burned patients. As a marker for sulphur amino acid deficiency, leucocyte glutathione, methionine and taurine concentrations and urinary excretion of sulphur amino acids and inorganic sulphate were followed in five severely burned patients during a 5-month period (1-6 months post injury). Reduced leucocyte concentrations of glutathione, methionine and taurine, and decreased urinary excretion of inorganic sulphate, methionine, cyst(e)ine and taurine were observed, and were most pronounced 2 or 3 months after injury. Simultaneously a minor decrease in urinary output and leucocyte concentration of branched-chain amino acids and serine were also found, whereas normal levels of glycine, threonine, and glutamine were registered. The episode of limited availability of sulphur amino acids coincides with the period of most intensive collagen and keratin resynthesis of burned skin tissue. PMID- 3108004 TI - Iron uptake by rat duodenal microvillous membrane vesicles: evidence for a carrier mediated transport system. AB - The mechanism of iron translocation from intestinal lumen to portal plasma is poorly understood. To examine these processes, uptake of Fe2+ and Fe3+ by rat duodenal microvillous membrane vesicles prepared by a Ca2+ precipitation procedure was studied. Membrane aliquots were incubated with increasing concentrations of 59FeCl3 in the presence of a one-thousand-fold molar excess of citrate or 59FeSO4 with a twenty-fold molar excess of L-ascorbic acid. After various time intervals the incubation reaction was stopped by addition of 0.1 mM FeCl3 (4 degrees C), and uptake of 59Fe was determined by a vacuum filtration assay. Initial uptake velocity of 59FeCl3 and 59FeSO4 was determined from the slope of the cumulative uptake curves, which was linear for the first 60 s. Initial uptake rates of both, 59Fe3+ and 59Fe2+ revealed an identical saturable uptake component with a Km of 19-22 nM and Vmax of 8 pmol min-1 mg protein-1. In addition, transport of Fe2+ revealed a linear unspecific uptake phase, which was predominant at high substrate concentrations. Saturable uptake of Fe2+ and Fe3+ was temperature dependent, and significantly reduced by trypsin pretreatment of the microvillous membrane vesicles, indicating the involvement of a protein in the uptake process. This suggestion was pursued by isolation of an iron binding protein from duodenal brushborder membranes. After solubilization of microvillous plasma membranes with 1% Triton X 100, affinity chromatography of the membrane protein mixture over an iron chelate gel derived from epoxy activated Sepharose and elution with 50 mM EDTA yielded a single 52,000 dalton protein. The protein co-chromatographed over an Ultro-Pac TSK G 3000SW HPLC column together with 59FeCl3 and 59FeSO4. It showed no immunologic activity to rabbit antibodies against whole rat serum or rat transferrin. Furthermore, by photoaffinity labelling technique a single iron binding protein with a molecular weight of about 52,000 dalton was identified in microvillous membranes of the rat duodenum. These data are compatible with the hypothesis that intestinal iron absorption is mediated by a specific carrier-dependent transport system. PMID- 3108005 TI - In-vivo studies on Haemaccel-fibronectin interaction in man. AB - An enzyme-linked immunoassay has been recently set up for direct measurement of the binding capacity of plasma fibronectin to gelatin. This binding capacity could be completely inhibited in vitro by an eight-fold excess of gelatin, of Haemaccel, but not of Geloplasma. On the contrary, the levels of immunoreactive fibronectin measured by laser nephelometry did not change, in presence of 10 to 1000 micrograms ml-1 of gelatin, of Haemaccel or of Geloplasma. When infused into normal volunteers, Haemaccel provoked a strong and immediate inhibition of the plasma fibronectin binding capacity to gelatin. This inhibition was dose dependent and maximal after infusion of 500 ml of Haemaccel. Twenty-four hours after this infusion, there was a progressive recovery of the gelatin-binding capacity, which was almost completely achieved 96 h later. The formation of complexes between Haemaccel and fibronectin was demonstrated by gel filtration chromatography and by affinity chromatography. Immunoreactive plasma fibronectin levels remained unchanged up to 24 h after infusion of 500 ml of Haemaccel. A transient decline to 50% of its initial value then occurred the second day after the infusion. Therefore, a delay existed between the formation of fibronectin Haemaccel complexes and their elimination from the bloodstream. This delay decreased when smaller volumes of Haemaccel were infused, which strongly suggests that plasma fibronectin is cleared by means of Haemaccel and does not seem to play a role of opsonin in these conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108007 TI - Effect of naloxone on the antral motor response to solid food in man. AB - Antroduodenal motor activity was recorded in eight healthy subjects using perfused tubes connected to external strain gauge transducers. Each subject was studied over a 2.5-h period following ingestion of a solid meal, on 2 separate days. Intravenous saline was administered on one day and saline plus naloxone (40 micrograms kg-1 h-1) on the other, in randomized order. Naloxone markedly inhibited the antral motor response to food and this effect was due to decreased amplitude and contractile frequency. The duodenal motor response to solid food and the postprandial rise in serum gastrin and plasma pancreatic polypeptide were not altered by naloxone. These observations suggest that peripheral or central opiate receptors play a role in regulating the antral motor response to food. PMID- 3108006 TI - Severe sodium restriction alone and with potassium supplementation does not alter blood lipoproteins in essential hypertension. AB - Seventeen 50-year-old men, previously untreated and all with mild to moderate essential hypertension, were given a low sodium diet for 2 weeks. During the second week, the diet was supplemented with potassium. Urinary excretion of Na+ decreased from 201 +/- 11 to 24 +/- 5 and 19 +/- 4 mmol 24 h-1, respectively, after 1 and 2 weeks (means +/- SE) while the urinary Na+: K+ ratio changed from 2:1 to 1:4 and 1:11. Despite significant changes in blood pressure, body weight, serum electrolytes, sympathetic noradrenergic tone, haemoglobin concentration and haematocrit, no significant change appeared in serum total cholesterol, HDL cholesterol or triglycerides. Thus, low sodium diet alone and combined with potassium supplementation seems neutral to blood lipoproteins in the treatment of essential hypertension. PMID- 3108008 TI - Ketanserin and the arterial baroreceptor reflex in normotensive subjects. AB - The effects of oral ketanserin 40 and 120 mg on the responses to baroreflex activation and deactivation by phenylephrine and nitroglycerin, respectively, were investigated in normotensive subjects. Plasma catecholamine levels were measured at the same times. Two hours after the administration of ketanserin, and regardless of its effect on arterial pressure (no change after 40 mg, decrease after 120 mg), there was no alteration either in resting heart rate or baroreflex sensitivity during baroreceptor activation or deactivation. The lack of reflex tachycardia in response to the drug-induced hypotension may be related to the alpha 1-adrenoceptor blockade-mediated sympathoinhibitory effect of ketanserin, which leaves unaffected both plasma catecholamines and the normal reactivity of the sympathetic system. PMID- 3108010 TI - Bioavailability of indomethacin from a modified release system containing indomethacin as the lysine salt. AB - The bioavailability of a new controlled release formulation of indomethacin lysine salt in tablets was tested in 6 healthy humans against a conventional indomethacin lysinate formulation in capsules. Both contained 100 mg of the drug, i.e. 70 mg indomethacin. Peak plasma levels were lower and more lasting and the AUC was higher with the new controlled release formulation. The latter on average produced active plasma levels for 12 h, and so it can be recommended for twice daily administration. PMID- 3108009 TI - New transdermal and transmucosal nitroglycerin delivery systems in patients with ischaemic heart disease. AB - The efficacy of a transdermal (Nitroderm-TTS) and a transmucosal (Trinitrolong) nitroglycerin (NG) formulation has been compared with sublingual NG in 9 patients with ischaemic heart disease and stable angina pectoris. The duration and the degree of anti-ischaemic effect were assessed in terms of similar, individually adjusted work loads performed prior to and repeatedly after drug application in comparison with placebo. The anti-ischaemic effect of nitroderm appeared in 0.5-3 h after administration, reached a maximum in about 3.8 h and persisted for 7.9 h. The maximal nitroderm effect was significantly lower than that of sublingual NG or Trinitrolong. The effect of Trinitrolong was less variable and lasted for 4.6 h. It was evident in all patients 0.5 h after drug administration. Plasma NG levels were monitored in 9 patients after sublingual NG and trinitrolong and in 4 following Nitroderm. The relative bioavailability of Nitroderm and Trinitrolong according to the pharmacokinetic data was 29% and 256%, respectively, of sublingual NG tablets. A therapeutic NG level in blood (0.5 ng/ml) after Trinitrolong appeared much earlier (2 min) than after Nitroderm (1 h). A significant reduction in the effect of sublingual NG was observed during Nitroderm application. Thus, the transdermal NG formulation did not exhibit an antianginal effect lasting for 24 h; transmucosal NG had a relatively short, but more pronounced and stable antianginal effect. PMID- 3108011 TI - Flecainide--an intravenous infusion regimen. AB - An intravenous infusion regimen for flecainide was studied in 12 patients. Therapeutic drug levels were rapidly established and maintained throughout the 48 h infusion period. Two patients were withdrawn because of possible drug related problems, but in general the regimen seemed both effective and well tolerated. PMID- 3108012 TI - Differences in diazepam pharmacokinetics in Chinese and white Caucasians- relation to body lipid stores. AB - We have compared diazepam pharmacokinetics in 16 Chinese and 18 white Caucasian healthy male volunteers, resident in Hong Kong and have correlated them with physical attributes. Serum concentrations of diazepam and desmethyldiazepam were measured in venous blood by an enzyme-linked immunoassay (0-3 h samples) and HPLC (3-72 h samples). Pharmacokinetic parameters were derived assuming a two compartment model, distribution phase less than 6 h, and 100% oral systemic availability. Compared with the Chinese the white Caucasians were older, heavier, taller, and fatter, as judged by skin fold thickness (SFT) and total body weight to 'Ideal' body weight (TBW/IBW) ratio; respective mean differences being 16%, 27%, 4%, 26%, and 15% (p less than 0.05). Mean diazepam apparent volume of distribution (V) and V/IBW were larger in the white Caucasians (52% & 39% respectively, p = 0.002). SFT and TBW/IBW ratio yielded the best correlations with V, V/TBW and V/IBW (0.50-0.75, p less than 0.05). Obesity indices contributed most to the overall regressions (R2 up to 0.52), and for V there was a further small effect (2%, partial F test) due to ethnic group, possibly reflecting stature. Mean peak diazepam concentration (Cmax) was similar in both ethnic groups. Time to Cmax (tmax) was more often prolonged in the Chinese (chi 2 test, p = 0.01). Body fat and stature may thus account for these inter-ethnic differences in the apparent volume of distribution of diazepam, a highly lipid soluble drug. PMID- 3108013 TI - Lack of relationship between sodium valproate-induced adverse effects and the plasma concentration of its metabolite 2-propylpenten-4-oic acid. AB - The concentrations of valproic acid (VPA) and of its metabolites 3-oxo-VPA and 4 en-VPA were measured in the plasma of 12 selected epileptic patients 1, 2, 3, and 4 h after administration of a loading dose of VPA. Four of the patients, all on polytherapy, had had short-term adverse effects during chronic VPA treatment, and in them there has been abnormal NH3-values after a test doese of VPA. Eight patients (4 on monotherapy and 4 on polytherapy) had been free from adverse effects. No significant difference in the VPA, 3-oxo-VPA and 4-en-VPA concentrations was found between the three groups of patients. Accumulation of 4 en-VPA is not involved in the short-term adverse effects and hyperammonaemia induced by VPA. PMID- 3108014 TI - The induction of class I HLA by interferon-alpha is independent of the cell cycle, but the expression is enhanced by a G1/S block. AB - The induction of class I HLA expression by interferon-alpha (IFN-alpha) was studied in lymphoid cells arrested or traversing different stages of the cell cycle. Exponential cultures of MOLT-4 cells and the MOLT-4 cell variant YHHH were treated with the cell cycle inhibitors aphidicolin and colcemid to obtain cell populations arrested in G1/S and G2/M, respectively, and also cells traversing from S to M and vice versa. Cytofluorimetry with the monoclonal antibody YTH/76.3 (which specifically detects those class I molecules which are most susceptible to IFN-alpha induction) was used to quantitate the class I HLA response to IFN alpha. The results showed that the response to IFN-alpha is not restricted to a given stage of the cell cycle. These studies also revealed that when the cells were arrested at G1/S, the absolute level of class I HLA expression was enhanced 2-3-fold, both in the presence or absence of either IFN-alpha or IFN-gamma. Therefore, even when absolute levels changed, the ratio of IFN-induced expression to basal expression remained constant at all cell cycle stages. The level of expression of another surface antigen (the CD1 antigen HTA-1) was not affected by the G1/S block. The results were confirmed by dot blot hybridization of poly(A)+ RNA using cDNA-specific probes. These findings suggest that the effect of IFN alpha is continuous throughout the cell cycle but that a G1-dependent event determines the extent of class I HLA expression, and leads to a synergistic superinduction by IFN in G1/S-arrested cells. PMID- 3108015 TI - Effective activation of resting mouse T lymphocytes by cross-linking submitogenic concentrations of the T cell antigen receptor with either Lyt-2 or L3T4. AB - We studied the activation of small resting mouse T lymphocytes by antibodies to the T cell antigen receptor in combination with antibodies to other T cell surface antigens. Solid-phase but not soluble antibodies KJ16-133 and F23.1, both directed to beta chains of the V beta 8 family, activate T cells to proliferate in the presence of growth factors, in a dose-dependent fashion. Antibodies to Lyt 2 and to L3T4 had no activating effect at any concentration. However, submitogenic concentrations of KJ16-133 and of F23.1 synergized with a wide range of concentrations of anti-Lyt-2 and anti-L3T4 to cause T cell proliferation similar or greater in magnitude to that caused by high concentrations of anti-T cell receptor antibody. Synergistic activation was also observed with antibodies to Lyt-1, LFA-1 and H-2 class I antigens but to a significantly lower degree. This was particularly clear in limiting dilution experiments in which the corrected frequencies of T cells proliferating in response to low amounts of anti T cell receptor antibody together with anti-Lyt-2 were 1/4 to 1/7 for BALB/c T cells. The frequencies of BALB/c T cells responding to high concentrations of anti-T cell receptor antibody alone were between 1/14 and 1/126 and still lower frequencies of T cells proliferated in synergistic responses with anti-LFA-1 or anti-Lyt-1. Synergistic activation leads to the induction of functional cytotoxic cells. We interpret these data as suggestive that cross-linking of the T cell antigen receptor with either Lyt-2 (CD8) or L3T4 (CD4) represents an optimal activating signal for resting T cells. We think that, in physiological T cell activation, cross-linking of the T cell receptor to CD8 or CD4 is induced by their simultaneous binding to major histocompatibility complex (MHC) class I (for CD8) or MHC class II (for CD4) molecules on stimulator cells. We consider the possibility that similar cross-linking requirements may also exist during T cell repertoire selection in ontogeny, thus accounting for the strict coexpression of MHC class I and class II-restricted T cell receptors with CD8 and CD4 molecules, respectively. PMID- 3108016 TI - Interleukin 2 pathway is autonomously activated in human T11+3-4-6-8- thymocytes. AB - Mitogenic membrane ligands have been shown to activate interleukin 2 (IL2) production only in mature T cells, IL2 constitutive secretion having not yet been demonstrated. Here we have isolated a population of T11+3-4-6-8- human thymocytes and CD7+/T11-3-4-6-8- prothymocytes which produce and consume IL2 upon phytohemagglutinin triggering. Interestingly, their proliferation in the absence of any exogenous stimulating agent was related to an autonomous use of the IL2 system (IL2 secretion and binding to its specific receptor, whose constitutive, functional expression in human early thymocytes was recently shown). The internal activation of this system before T cell receptor acquisition stresses the relevance of the understanding of the alternative activation pathway(s) in T cell development. These findings, together with the demonstration of IL2-promoted differentiation of human early thymocytes into mature T cells, suggest that IL2 may also be a growth and differentiation factor acting specifically early in T cell development. PMID- 3108017 TI - DNA fragmentation and cytotoxicity caused by tumor necrosis factor is enhanced by interferon-gamma. AB - Recombinant human tumor necrosis factor (rhuTNF) induced DNA fragmentation in sensitive cell lines. This fragmentation was similar to that caused by lymphotoxin-containing cytotoxic T cell culture supernatants. The percentage of DNA cleaved correlated with the degree of cell growth inhibition shown by individual cell lines. DNA fragmentation was first seen after 12 h treatment, and increased slowly with time. The presence of 100 microM ZnSO4 inhibited the rhuTNF induced DNA cleavage in MCF-7 cells. Recombinant interferon-gamma (rhuIFN-gamma) did not induce DNA cleavage, although it reduced the growth of all the cell lines used in this study. However, it interacted with rhuTNF to produce a doubling in the percentage of DNA fragmentation, and increased cytotoxicity in rhuTNF sensitive cell lines. Pretreatment with rhuIFN-gamma for 1 h prior to rhuTNF treatment also enhanced DNA fragmentation and cell killing. PMID- 3108018 TI - The effect of recombinant interferon-gamma on human monocyte-derived macrophages. AB - The effect of recombinant interferon-gamma (rIFN-gamma) on human macrophage functions was studied, using monocytes which had matured to macrophages within hydrophobic containers. Following exposure to rIFN-gamma, the number of surface expressed specific IgG-binding sites was increased. This increase was restricted to high-affinity Fc receptors (FcR), however; low-affinity FcR were not increased in number. Exposure to rIFN-gamma led to an enhanced chemiluminescence (CL) signal in the presence of luminol and a variety of respiratory burst stimuli, such as zymosan, phorbol 12-myristate 13-acetate or IgG-sensitized sheep erythrocytes (EA). In contrast, phagocytosis of EA was markedly depressed in rIFN gamma-treated cells. Both increase in CL response and decrease in phagocytic activity were manifest after 1 day of treatment and were more pronounced after 2 days. While 5 U/ml of rIFN-gamma was an insufficient dose, 50 to 5000 U/ml yielded significant dose-dependent changes in both functional assays. Thus, using rIFN-gamma as a biological response-modifier, FcR expression and FcR-mediated CL can be dissociated from FcR-mediated phagocytosis. PMID- 3108019 TI - Cardiac M2 receptors consist of two different types, both regulated by GTP. AB - Cardiac muscarinic receptors are predominantly M2 receptors, and have three agonist binding sites (super-high(SH), high(H) and low(L) affinity agonist binding sites). Treatment of cardiac membranes with 50 nM propylbenzilyl choline mustard (PrBCM) caused 88% loss of binding sites for [3H]QNB. Carbamyl choline (CCh) inhibits this alkylation dose dependently and, theoretically, generates uneven alkylation of multiple agonist binding sites. Pretreatment of the membranes with 50 nM PrBCM and 0.5 mM CCh resulted in almost complete disappearance of L sites with similar degrees of conservation of H sites and SH sites. In these pretreated membranes, guanine nucleotide and sulfhydryl reagent caused a change in the ratio of residual SH and H sites but not of L sites though previous studies showed that, in intact membranes, these reagents affected the ratio of SH and L sites without significantly changing that of the H site. These results indicate the existence of two equilibria regulated by guanine nucleotide and sulfhydryl reagent in cardiac muscarinic receptors: one between SH and H sites and the other between H and L sites. The participation of GTP binding protein(s) in all cardiac muscarinic responses is suggested. PMID- 3108021 TI - N-acetylcysteine and 2-mercaptoethane sulphonate inhibit anti-pseudomonas activity of antibiotics in vitro. AB - The in vitro activity against Pseudomonas aeruginosa was investigated for serial dilutions of eight anti-Pseudomonas antibiotics in combination with serial dilutions of N-acetylcysteine (NAC) and 2-mercaptoethane sulphonate (MES). The results indicated that addition of NAC and MES to the antibiotics increased the MIC values for tobramycin, netilmicin, piperacillin, azlocillin, cefsulodin, ceftazidime and imipenem but not for colistin. The decrease of MIC found in high concentrations of NAC and MES was probably due to the bacteriostatic effect of the drugs per se and not to synergism with the antibiotics. PMID- 3108020 TI - Morphological and functional effects of Na2EDTA on the outflow routes for aqueous humor in monkeys. AB - The chelating agent Na2EDTA was perfused through the anterior chambers of monkeys eyes in an attempt to find a concentration that would cause a rise in outflow facility without harming the cornea or anterior uvea. Na2EDTA (0.5 mM) proved effective in increasing the facility within 60 min. There were marked effects on the tissue at the iridocorneal chamber angle with loss of cell processes from the trabecular cells, ballooning of the juxtacanalicular region and the inner wall of Schlemm's canal into the canal and ruptures of the inner wall of Schlemm's canal. After 60 min of perfusion there were mild vascular changes in the ciliary muscle and the iris and more pronounced stasis and leukocyte extravasation at the base of the ciliary processes and in the pars plana region. The corneal endothelium tended to swell but only after prolonged perfusion. After interruption of the perfusion there was rapid reduction in outflow facility, that seemed to be due to occlusion of the ruptures in Schlemm's canal by thrombocytes. PMID- 3108022 TI - A possible mechanism for binocular depth judgements in anurans. AB - Two experiments were performed to analyze how anurans (Bufo marinus) use binocular cues to gauge the distance of their prey. In the first, bilateral lesions of the nucleus isthmi eliminated the major source of input from the ipsilateral eye to the tectum. These lesions did not disrupt the animals' ability to use binocular cues to judge distance, suggesting that frogs and toads may not employ binocular disparity-selective cells to assess prey distance. They may instead use a scheme more overtly akin to triangulation, with each tectum providing an output signal encoding the angular position of the prey with respect to the contralateral eye and with distance extracted from the difference between these tectal outputs. In the second experiment, prisms imposed large (13.5 degrees) vertical disparities between the two eyes' images. The toads continued to use binocular cues. The added vertical disparities, like added horizontal ones, caused toads to undershoot their prey. Thus the binocular system must tolerate such vertical disparities and fail to distinguish them from horizontal ones. PMID- 3108023 TI - Photoreceptor degeneration during infection with various strains of the scrapie agent in hamsters. AB - Hamsters were inoculated intracerebrally with the 22C, 79A, and ME7 strains of the scrapie agent to compare the effects on the retina with those caused by strain 263K. The animals developed clinical signs of encephalopathy. Photoreceptor degeneration occurred in all experimental animals. The changes were similar to those seen in animals infected with the 263K strain of scrapie although somewhat more variable and less extensive. PMID- 3108024 TI - Schistosoma spp.: progress toward a defined vaccine. AB - During the last 2 decades, much was learned concerning the nature of acquired immunity in schistosomiasis, under experimental as well as field conditions. The knowledge is being applied now to design of a defined vaccine against this major parasitic disease. Several Schistosoma spp. antigens have been purified and shown to potentially protect in vivo. Determination of a method for presenting these antigens that will induce an optimal combination of cellular and humoral immune responses remains a critical step in vaccine development. PMID- 3108025 TI - HBV pre-vaccination screening in hospital personnel: cost-effectiveness analysis. AB - The purpose of this study was to identify the most cost-effective method for screening subjects for hepatitis B vaccination. Such a method would ideally permit detection of all susceptible individuals at the lowest possible cost. Two hundred-five hospital workers from the Piedmont region of Italy participated in the study. The sero-epidemiological conditions of this group with regard to hepatitis B markers was representative of hospital workers in this region as a whole. All subjects, excluding carriers, persons with anti-HBs titers greater than or equal to 10 mIU and subjects positive for anti-HBc at a 1/100 dilution, were vaccinated. Their responses were evaluated 15 days and 1 month after vaccination. The presence of a booster effect following vaccination was correlated with the immunological status of the subject at the time of pre vaccination screening. In the light of the results obtained, 5 screening procedures and the procedure of vaccination without screening were evaluated. The most cost effective screening strategy proved to be that of sequential testing for anti-HBc, anti-HBs and finally HBsAg and vaccination of the following subjects: those who were negative for anti-HBc, those who were anti-HBc-positive with anti-HBs titers 10 less than mIU and those who were HBsAg negative. PMID- 3108026 TI - Multiple myeloma: light chain isotype suppression--a marker of stable disease at presentation. AB - Prognosis in multiple myeloma (MM) is related to the establishment of an immunologically and kinetically characteristic plateau phase. Patients who present with this state may not benefit from immediate chemotherapy. We assessed 20 patients with MM who were staged according to the Salmon and Durie classification at diagnosis and monitored throughout the course of their disease. Patients with a lambda paraprotein and a kappa/lambda lymphocyte ratio in the blood greater than 4.0 were considered to demonstrate light chain isotype suppression (LCIS). Similarly, patients with a kappa paraprotein and a kappa/lambda ratio of less than 0.55 were also considered to have LCIS (1). 14 patients had LCIS; of these, 6 were classified as stage IA, 2 as stage IB, 3 as stage IIA, and 3 as stage IIIA. 6 patients did not have LCIS; 3 were classified as stage IIA, 1 as stage IIIA and 2 as stage IIIB. 10 patients with LCIS were assessed for treatment benefit following administration of melphalan and prednisone, as defined by a fall in the serum paraprotein level of greater than 50% over 6 months. In 8 patients the serum paraprotein levels did not fall, and the patients remained in good health without clinical deterioration. Thus LCIS at presentation may indicate patients in whom treatment can be safely deferred or in whom aggressive therapy is not indicated. PMID- 3108027 TI - An IgG kappa-monotypic anti-Pr 1h associated with fresh varicella infection. AB - The first cold agglutinin occurring in an adult patient with fresh varicella infection is described. The antibody caused a hemolytic crisis. It had anti-Pr 1h specificity. It belonged to the rare cold agglutinins of the IgG class and was a kappa-monotypic (monoclonal) antibody. PMID- 3108028 TI - [Reinduction of the cytochrome P-450 system of the liver in rats exposed to polychlorinated biphenyls during starvation]. AB - Contents of cytochrome P-450 and b5, rates of oxidation of aniline, amidopyrine and dimethylaniline as well as activities of NADP-H- and ascorbate-dependent systems of lipid peroxidation (LPO) in rat liver microsomes five months after single administration of the mixture of polychlorinated diphenyls (PCD) significantly exceeded the control level. Starvation of the animals for 120 hours led to an additional increase of cytochrome P-450 content and LPO activation. The rat liver monooxygenase system retained the ability to respond to the inducing action of the mixture of PCD (500 mg/kg) during starvation. PMID- 3108029 TI - The amino acid sequence of the aliphatic amidase from Pseudomonas aeruginosa. AB - Amino acid sequence studies show that the aliphatic amidase (EC 3.5.1.4) from Pseudomonas aeruginosa PAC142 consists of a single polypeptide chain of 346 residues, giving an Mr of 38,400. The evidence from the amino acid studies is in complete agreement with that deduced from the DNA sequence of the amiE gene. Studies of the protein from Pseudomonas putida A87 show that it differs from the Ps. aeruginosa protein by about 30 amino acid substitutions. It now becomes possible to relate changes in the enzyme which result in altered specificity to structural changes in the protein. PMID- 3108030 TI - The nucleotide sequence of the amiE gene of Pseudomonas aeruginosa. AB - The nucleotide sequence of the amiE gene, encoding the aliphatic amidase of Pseudomonas aeruginosa, has been determined. The sequence of 1038 nucleotides shows a strong bias in favour of codons with G or C in the third position, and only 44 different codons are utilised. PMID- 3108031 TI - Presence of three pertussis toxin substrates and Go alpha immunoreactivity in both plasma and granule membranes of chromaffin cells. AB - GTP-binding proteins have been proposed to be involved in some secretory processes. Bordetella pertussis toxin is known to catalyze ADP-ribosylation of several GTP-binding proteins. In this paper, the subcellular localization of B. pertussis toxin substrates has been explored in chromaffin cells of bovine adrenal medulla. With appropriate gel electrophoresis conditions, three ADP ribosylated substrates of 39, 40 and 41 kDa were detectable in both plasma and granule membranes. The more intense labelling occurred on the 40 kDa component, while the 41 kDa species exhibited electrophoretic mobility similar to that of Gi alpha. Significant immunoreactivity with anti-Go alpha antibodies was detected at the level of the 39 kDa faster component. The association of G-proteins with granule and plasma membranes suggests the involvement of these proteins in the exocytotic process or in its regulation. PMID- 3108032 TI - Adenylate cyclase of bovine adrenal cortex plasma membranes. Divergence between corticotropin and fluoride combined effects with forskolin. AB - The diterpene forskolin maximally stimulated bovine adrenal cortex adenylate cyclase activity 9-fold with a concentration producing half-maximum effect (ED50) of about 4 microM. The effects of forskolin and the fully active corticotropin fragment ACTH (I 24) were additive over nearly the whole range of concentration of both effectors, indicating separate and independent mechanisms of action. By contrast, 10 mM NaF blocked forskolin action in the nanomolar range of the diterpene concentration, while it allowed a partial stimulation by forskolin in the micromolar range. NaF thus reveals a heterogeneity of forskolin action in the adrenal cortex plasma membranes. Moreover, our data suggest that ACTH and NaF activation effects, both mediated by the stimulatory regulatory protein Gs, proceed through different mechanisms. PMID- 3108033 TI - The kinetics of calcium binding to fura-2 and indo-1. AB - The kinetics of Ca2+ dissociation from fura-2 and indo-1 were measured using a stopped-flow spectrofluorimeter. The dissociation rate constants were 84 s-1 and 130 s-1, respectively, in 0.1 M KC1 at 20 degrees C. The rate constants were insensitive to pH over the range 7.0 to 8.0. The second order association rate constants were estimated indirectly to be in the region of 5 X 10(8) M-1 X s-1 and thus approach the diffusion-controlled limit. The results demonstrate that these new generation indicators are well-suited to measure rapid changes in concentration of intracellular Ca2+. PMID- 3108035 TI - Intracellular stimulation of mast cells with guanine nucleotides mimic antigenic stimulation. AB - Exocytosis was followed in single rat peritoneal mast cells, by measuring the cell membrane capacitance using circuit analysis and patch-clamp techniques. After antigenic stimulation or intracellular perfusion with guanine nucleotides, exocytosis followed a time course characterized by a lag period d, area expansion factor A, and a time constant tau. We suggest that A depends entirely on the cell's morphology, d reflects the properties of a GTP-binding regulatory protein that appears to rate limit the response and tau is due to an independent and yet unknown process. In contrast, cells stimulated by compound 48/80 can respond without a measurable delay and degranulate within 2 s, suggesting that this compound acts at a site after the GTP-binding regulatory protein. PMID- 3108034 TI - PA-II, the L-fucose and D-mannose binding lectin of Pseudomonas aeruginosa stimulates human peripheral lymphocytes and murine splenocytes. AB - Pseudomonas aeruginosa lectin PA-II agglutinates human peripheral lymphocytes and stimulates mitogenesis (predominantly in T cells), like the plant lectins PHA and Con A. Murine splenocytes are also agglutinated and stimulated by PA-II as by Con A. Sialidase treatment of the human and murine cells enhances their agglutination and augments the stimulation of human lymphocytes at low PA-II concentrations. The PA-II agglutinating and mitogenic effects are specifically inhibited by L fucose. The bacterial source and the specificity of PA-II for L-fucose are both rare features among the hitherto described mitogenic lectins. However, since this lectin also binds mannose, a mannose-bearing receptor might be involved in its mitogenicity. PMID- 3108036 TI - Cleavage of the Arg-Ile bond in the native polypeptide chain of human pancreatic stone protein. AB - The pancreatic stone protein (PSP) isolated from calculi (Mr 14,000) and the 5 protein forms (PSP S1-5) detected in pancreatic juice (Mr 14,000-19,000) derive from the same source differing seemingly in their carbohydrate contents or/and in their polypeptidic chain lengths. This kind of protein would inhibit in vivo CaCO3-crystal growth in pancreatic juice. PSP and PSP S1 N-terminal sequences are identical (NH2Ile-). This report demonstrates that: in PSP S2-5 the amino terminal is blocked; the C-terminus is alike in every form; the single polypeptide chain of PSP S2-5 is converted into that of PSP S1 or PSP by the specific trypsin cleavage of the Arg-Ile bond. PMID- 3108037 TI - ADP-ribosylation of specific membrane proteins in pheochromocytoma and primary cultured brain cells by botulinum neurotoxins type C and D. AB - Type C1 and D toxins produced by Clostridium botulinum caused ADP-ribosylation of a protein of 24 kDa in membrane preparations of rat clonal pheochromocytoma cells (PC12) and of proteins of 25 and 26 kDa in neuron-rich culture of fetal rat brain cells. The ADP-ribosylation reaction was dependent on the presence of MgCl2, GTP and GTP gamma S. The results obtained suggested that the ADP-ribosylation reaction is responsible for the development of the biological activity of the botulinum neurotoxins and that the target of this reaction may be novel GTP binding proteins localized on cell membranes. PMID- 3108038 TI - [Hygienic significance of air environmental factors]. PMID- 3108040 TI - [Secretion of cefsulodin and moxalactam in the saliva]. PMID- 3108039 TI - [Effect of stimulation of the posterior hypothalamic nuclei on the cell proliferation of immunocompetent organs and the beta radioactivity of the blood after DMBA exposure]. PMID- 3108041 TI - [Effect of preliminary enzymatic hydrolysis of enterically introduced mixtures of natural food products on the absorption of their nitrogenous component]. PMID- 3108042 TI - Significant increase of urinary low-sulfated heparan-sulfate-related protein in patients with severe systemic scleroderma. AB - Radioimmunoassay with an antibody produced against urinary low-sulfated heparan sulfate-related protein was devised and used to screen the heparan sulfate level in the urine of patients with systemic scleroderma. Patients with diffuse scleroderma, and patients also showing polymyositis/dermatomyositis had elevated values, whereas the value in patients with acrosclerotic scleroderma did not differ from that of the control population. In addition, an increase in this protein was associated with the positivity of anti-Scl-70 antibody. These findings suggest an important role for low-sulfated heparan sulfate in the pathobiology of severe systemic scleroderma. PMID- 3108043 TI - Eicosanoids in psoriasis--15-HETE on the stage. PMID- 3108044 TI - Are Lisch nodules an ocular marker of the neurofibromatosis gene in otherwise unaffected family members? AB - A male patient with classical neurofibromatosis is reported. Examination of the other family members revealed 2 patients with solitary cutaneous neurofibromas and 2 with one or more Lisch nodules without other cutaneous or systemic signs of neurofibromatosis. This suggests that Lisch nodules can be a marker for the neurofibromatosis gene in otherwise unaffected family members. PMID- 3108045 TI - Choice of an ovarian stimulation protocol according to the follicular puncture method in an in vitro fertilization programme. AB - In order to ascertain the adequacy of ovarian stimulation protocols with a type of follicular puncture, 126 women undergoing in vitro fertilization received either combination clomiphene/hMG or hMG alone according to a randomized test protocol. Within both groups patients for whom a pelvic examination was required had laparoscopies, while others had transvaginal ultrasonically guided punctures as far as possible. Clomiphene/hMG was more efficient than hMG alone as assessed from the cleavage rate (68% vs. 54%; p less than 0.01) and the pregnancy per attempt rate (16% vs. 5%; p less than 0.05). Laparoscopic punctures were more efficient than ultrasonically guided punctures (mean number of recovered oocytes: 4.8 +/- 2.6 vs. 3 +/- 2.5; p less than 0.001), but slightly better results were achieved by this latter method in ongoing pregnancy per puncture rate (18% vs. 8%; NS). With ultrasonically guided punctures, stimulation by clomiphene/hMG allowed better oocyte recoveries (3.8 +/- 2.5 vs. 2.3 +/- 1.9, p less than 0.05). Such results constitute an argument for preferential use of the clomiphene/hMG stimulation protocol with ultrasonically guided punctures. PMID- 3108046 TI - A late developmental change in lysosomal enzyme sulfation specific to newly synthesized proteins in Dictyostelium discoideum. AB - During development in Dictyostelium discoideum, several lysosomal glycosidases undergo changes in post-translational modification that are thought to involve differences in the extent of sulfation or phosphorylation, and appear to be required for the maintenance of cellular enzyme activity late in development. We have used monoclonal antibodies specific to the lysosomal enzyme alpha mannosidase-1 to study the major late (12 hr) developmental change in the modification system. Pulse-chase experiments performed both early and late in development reveal that the substrate for the late form of modification is restricted to newly synthesized alpha-mannosidase-1 precursor protein. We have identified one modification difference between the two developmentally distinct isozymes of alpha-mannosidase-1: 35SO4 pulse-chase data show that the newly synthesized "late" enzyme precursor is significantly undersulfated in comparison with the enzyme synthesized early in development. This apparent lack of sulfation is associated with the lack of acquisition of endoglycosidase H resistance. By contrast, an aggregation-deficient mutant, which is defective with regard to the accumulation of alpha-mannosidase-1 activity late in development, synthesizes the "early" sulfated form of the enzyme throughout development. We conclude that the late developmental change in post-translational modification specifically involves one of the biochemical steps in which the N-linked oligosaccharide side chains of the newly synthesized alpha-mannosidase-1 precursor are modified by sulfation. PMID- 3108047 TI - Ovoperoxidase assembly into the sea urchin fertilization envelope and dityrosine crosslinking. AB - Ovoperoxidase, the enzyme implicated in hardening the extracellular coat of the fertilized sea urchin egg, is inserted into the assembling uncrosslinked (soft) fertilization membrane via specific interactions with a protein, proteoliaisin (P. Weidman, E. Kay, and B. M. Shapiro (1985). J. Cell. Biol. 100, 938-946), and the vitelline scaffold. Dityrosine crosslinks introduced by ovoperoxidase have been postulated to harden the assembled structure from such indirect data as the discovery of dityrosine in hard fertilization membranes (Foerder and B. M. Shapiro (1977). Proc. Natl. Acad. Sci. USA 74, 4214-4128; H. G. Hall (1978). Cell 15, 343-355). In this report, we show directly that soft fertilization membranes (SFM) contain no dityrosine residues but acquire these crosslinks in vitro only during hardening. In vitro hardening alters the susceptibility of the fertilization membrane to disruption in cation-depleted solutions and in detergent; the kinetics of these phenomena are all similar to those of hardening in vivo. Ovoperoxidase substrates were identified as a class of high-molecular weight proteins of SFM by polyacrylamide gel electrophoresis after in vitro hardening or after an ovoperoxidase-catalyzed radioiodination reaction. The specificity of ovoperoxidase for particular substrates decreased once it was no longer associated with these polypeptides within the SFM. Moreover, after disruption of the SFM, ovoperoxidase had an increased capacity to iodinate an exogenous protein, myoglobin. These data suggest that assembly of ovoperoxidase into a specific locus within the soft fertilization membrane provides a regulatory mechanism to guarantee the crosslinking of only certain appropriately juxtaposed tyrosyl residues in the assembled structure. PMID- 3108048 TI - 7C female sterile mutants fail to accumulate early eggshell proteins necessary for later chorion morphogenesis in Drosophila. AB - Seven noncomplementing female sterile mutations that affect eggshell assembly in Drosophila have been mapped to the 7C1-3 region of the X-chromosome. TEM of the mature eggshell of one of the alleles, fs(1)410, shows a lack of organization within the endochorion and an accumulation of electron dense material in the vitelline membrane of stage 14 eggchambers. SDS-PAGE of radiolabeled eggshell proteins shows that two proteins, s67 and s85, fail to accumulate in the fs(1)410 eggshell. In wild-type flies s85 is produced during stage 10 of oogenesis and then processed to s67 in stages 13 and 14. Neither s85 nor an additional stage 10 specific follicle cell protein (s130) are detected in fs(1)410 or four of the mutant alleles. Short-term labeling studies, analyses of in vitro translation products, and the simultaneous occurrence of s85 and s130 as electrophoretic variants in geographic fly strains indicate s85 is derived from s130. Although major biochemical differences appear in stage 10, mutant and wild-type eggshells are morphologically indistinguishable until stages 13-14. These results suggest that follicle cell proteins synthesized during the time of vitelline membrane deposition (stage 10) are important for proper assembly of the chorion layers during stages 13 and 14. PMID- 3108049 TI - Expression of epidermis-specific antigens during embryogenesis of the ascidian, Halocynthia roretzi. AB - We have produced two monoclonal antibodies (Epi-1 and Epi-2) which specifically recognize epidermal cells and their derivative, the larval tunic, of developing embryos of the ascidian Halocynthia roretzi. The antigens, examined by indirect immunofluorescence staining, first appear at the early tailbud stage and are present until at least the swimming larval stage. There were distinct and separate puromycin and actinomycin D sensitivity periods for each antigen. Aphidicolin, a specific inhibitor of DNA synthesis, prevented the appearance of each antigen when embryos were exposed to the drug continuously from cleavage stages. These results suggest that the antigens are synthesized during embryogenesis by developing epidermal cells and that several rounds of DNA replication are required for the antigen expression. Early cleavage stage embryos, including fertilized but unsegmented eggs, in which cytokinesis had been blocked with cytochalasin B expressed the antigens, and blastomeres exhibiting the antigens were always of the epidermis lineage. In partial embryos produced by four separated blastomere pairs of the 8-cell embryos, the expression of antigens was seen only in those developed from the animal blastomere pairs, which are progenitors of epidermal cells. These observations indicate that differentiation of epidermal cells in ascidian embryos takes place in a typical "mosaic" fashion. PMID- 3108050 TI - Immunohistochemical characterization of delta crystallin-containing retina/optic nerve "boundary" cells in the chick embryo. AB - The term "transdifferentiation" has been used to describe the apparent phenotypic conversion of chick embryo neural retina Muller glial cells into lens-like cells in vitro. This phenotypic conversion is characterized by expression of such lens specific proteins as delta crystallin and has been viewed as an example of cells transforming from the phenotype of a given tissue to that of another. We have identified a population of neuroglia-like cells in the embryonic chick retina which express high levels of delta crystallin as a function of normal development. The position and morphology of these cells is quite distinctive in that they form a loose meshwork which defines the boundary between the neural retina and the optic nerve head. These "boundary" cells are detectable as early as Day 5 of development through hatching. However, the meshwork structure formed by the cells is only readily observed between Days 8 and 9 of development. Double immunolabeling procedures comparing delta crystallin staining to that of glial and neuronal markers suggest that these cells are a form of retinal Muller glial cell. The results show that under appropriate microenvironmental conditions, expression of delta crystallin falls into the normal repertoire of retinoblast cells. The results also demonstrate the presence of a cellular boundary defining the junction between the neural retina and the optic nerve, tissues that are ontogenetically and structurally continuous but functionally distinct. PMID- 3108051 TI - Immobilized animal cells. PMID- 3108052 TI - Cultivation of Bowes melanoma cells in the Opticell system: influence of the addition of protein supplements to the serum-free medium on the production of plasminogen activator. AB - The influence of a protein-free and a protein-rich, supplemented serum-free medium on the production of plasminogen activator (t-PA) from Bowes melanoma cells was investigated in the Opticell culture system and compared to tissue culture flask cultures. In the presence of medium supplements metabolic activity and t-PA production were favoured in both systems. The addition of supplements was apparently more effective in the Opticell than in flask cultures, because t PA activity obtained in the Opticell was 2-3 times higher in protein-rich medium, but 2 times lower in unsupplemented medium than in flasks. These results indicate that the protein content in a serum-free medium is important for product formation in the Opticell, and serum-free media which work at small scale in tissue culture flasks are not always suited for technical culture systems such as the Opticell but have to be adapted to them. PMID- 3108053 TI - Process-scale purification from cell culture supernatants: monoclonal antibodies. AB - A method for processing monoclonal antibodies (mAb) from large volumes of cell culture supernatants using recently developed high performance and fast flow chromatography media is described. A high-antibody producing mouse hybridoma cell line was adapted to low serum containing medium (1% foetal calf serum) for the production of anti-tissue Plasminogen Activator (anti-tPA) monoclonal antibody (murine subclass IgG1). The process consisted of three main chromatographic steps: desalting, cation exchange on S Sepharose Fast Flow and gel filtration on Superose 6 prep grade. With this process for the purification of anti-tPA monoclonal antibody, the final product was greater than 95% pure with a total recovery of 75% i.e. 1.4 g was recovered in 0.345 l from 35 l of culture supernatant originally containing 1.9 g of mAb. The adaptation of this process for purification of other monoclonal antibodies is discussed. PMID- 3108054 TI - Human cell lines secreting lymphokines. I. Establishment of T-T hybridomas. AB - Lymphokines (Lks) are conventionally produced by mitogen stimulation of T lymphocytes. However, this procedure results in a mixture of factors, some of which may have antagonistic effects. An alternative method of producing Lks is the construction of monoclonal T-T hybridomas which secrete distinct Lks. By adapting the hybridoma technology for T cells, one can select distinct T hybridomas which may serve as constant sources for the production of uniform and well defined Lks. Since the compatibility of a certain cell line to serve as a fusion partner is unpredictable, several lines were tried in the hybridization procedure. An obligatory requirement of such a mutant line is its sensitivity to a selective medium, in which only the hybrid cell would survive. For this purpose three 8-azaguanine (8AG) resistant mutant lines (Jurkat/12 CEM/14 and Molt-4/10) were established from the respective T leukemic cell lines. This was achieved by culturing the cells in the presence of 200 microM 8AG. The surviving resistant cells were sensitive to aminopterin and azaserine inhibitors. Depending on the cell line and the inhibitor, death of these mutants was complete in 7 to 14 days. Non-adherent peripheral blood lymphocytes (PBL) stimulated for 48 hours with 1 microgram/ml phytohemagglutinin (PHA), were fused with the CEM/14 line. Fifteen hybridomas secreted a substance with B cell growth factor (BCGF) activity, nineteen hybridomas secreted T cell growth factor (IL-2), and eight hybridomas secreted gamma-interferon (gamma-IFN). The six lines which exhibited BCGF activity only, were expanded and cloned. The BCGF activity in the supernatant of a positive clone, designated TH-5, was found to be 3-fold more potent than a preparation of BCGF obtained by stimulation of PBL with PHA. PMID- 3108055 TI - Screening for monoclonal antibodies with covalently linked antigen. AB - Microtitre plates prepared for ELISA are treated for the maximum adsorption of gamma-globulins (at pH 9). The adsorption of other soluble proteins (e.g. antigens) is sometimes less effective and therefore requires a higher amount of protein for the primary coat of wells. In order to reduce the amount of pure antigen required for the screening of mAb-producing hybridomas, we improved the sensitivity of our screening ELISA technique by coupling the antigen covalently to the surface of the microtiter wells. The antigen (urokinase) was coupled by the glutaraldehyde or carbodiimide procedures respectively using "aminoplates" (Nissho Iwai, Japan). The glutaraldehyde method led to at least a five fold increase of the sensitivity compared to coventional adsorption. Reduced requirement of antigen for the assay is thus achieved by a simple procedure. PMID- 3108056 TI - A rapid and sensitive method for the detection of mycoplasmas in infected cell cultures using 6-methyl purine deoxyriboside. AB - 6MPDR causes the death of cells lightly infected with mycoplasmas. This is brought about by the action of the mycoplasmal enzyme adenosine phosphorylase which converts 6MPDR to highly toxic metabolites. If the medium conditions are adjusted to favour the growth of mycoplasmas by the addition of pig serum to the medium, infections as low as 1 mycoplasma per 200,000 cells can be detected within 7 days. This finding enables mycoplasma tests to be carried out rapidly and reliably by untrained personnel. PMID- 3108057 TI - Amphetamine reverses learning deficits in 6-hydroxydopamine-treated rat pups. AB - At 5 days of age, rat pups were treated with a combination of desmethylimipramine (DMI) and 6-hydroxydopamine (6-OHDA) to selectively deplete brain dopamine (DA) or with vehicle (saline) control solutions. Two days later, all animals received conditioning to a novel odor by pairing the odor with intraoral milk. When the odor was anise, treated pups spent less time near the conditioned stimulus than did controls, but there were no 6-OHDA effects when the stimulus was a lemon odor (Experiment I). The difference in performance between the treated and control animals was not attributable to alterations in activating effects of the reinforcer (Experiment I), changes in olfactory sensitivity or olfactory preference (Experiment II), or sensitization to the stimulus (Experiment III). In Experiment IV, animals received d-amphetamine sulfate (0.5 mg/kg) prior to conditioning, testing, or both conditioning and testing. Amphetamine treatment before conditioning produced an improvement in performance in animals previously treated with 6-OHDA/DMI, but it impaired performance in controls, regardless of the time of injection. The results indicate a role of brain DA in learning in young rats. PMID- 3108059 TI - Joint venture makes new wing a reality. PMID- 3108058 TI - Increased vascular permeability in spontaneously diabetic BB/W rats and in rats with mild versus severe streptozocin-induced diabetes. Prevention by aldose reductase inhibitors and castration. AB - 125I-labeled albumin permeation (IAP) has been assessed in various tissues in spontaneously diabetic insulin-dependent female BB/W rats and in male Sprague Dawley rats with severe or mild forms of streptozocin-induced diabetes (SS-D and MS-D, respectively). In BB/W diabetic rats and in rats with SS-D, indices of IAP were significantly increased in tissues and vessels predisposed to diabetic vascular disease in humans, including the eyes (anterior uvea, posterior uvea, and retina), sciatic nerve, aorta, kidney, and new vessels formed after induction of diabetes. No evidence of increased IAP was observed in heart, brain, testes, or skeletal muscle in BB/W or SS-D rats. In MS-D rats, indices of IAP were increased only in the kidney and in new vessels formed after the onset of diabetes. Marked tissue differences were observed in the effects of two structurally different aldose reductase inhibitors (sorbinil and tolrestat) and of castration on diabetes-induced increases in IAP and in tissue levels of polyols in SS-D rats. Both aldose reductase inhibitors and castration completely prevented diabetes-induced increases in IAP in new vessels and in sciatic nerve in BB/W and SS-D rats. Both aldose reductase inhibitors also markedly decreased IAP in the anterior uvea (approximately 85%), posterior uvea (approximately 65 75%), retina (approximately 65-70%), and kidney (approximately 70-100%); castration reduced IAP in the anterior uvea (approximately 55%), kidney (approximately 50%), and retina (approximately 30%) but had no effect on the posterior uvea. The diabetes-induced increases in IAP in the aorta were reduced only slightly (approximately 20%) by aldose reductase inhibitors and castration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108061 TI - Renal subcapsular versus portal vein site for islet transplantation in mice. PMID- 3108060 TI - Changes in the factor VIII complex in diabetic ketoacidosis: evidence of endothelial cell damage? AB - Factor VIII-related antigen and von Willebrand factor are synthesised by and released from vascular endothelium. Acute increases in the plasma concentration of these proteins may reflect endothelial cell damage. We have thus measured the plasma concentration of factor VIII-related antigen and von Willebrand factor, together with procoagulant factor VIII, during the course of acute diabetic ketoacidosis in seven patients. In addition, evidence for qualitative changes in the factor VIII complex was sought. Plasma factor VIII-related antigen and von Willebrand factor were markedly increased (plasma factor VIII-related antigen at presentation, median 2.75 U/ml; von Willebrand factor 2.95 U/ml) and returned toward normal with clinical and biochemical resolution (plasma factor VIII related antigen at clinical recovery, median 1.80 U/ml; von Willebrand factor 2.05 U/ml). Plasma procoagulant factor VIII followed a similar pattern, but levels were less elevated (plasma procoagulant factor VIII, at presentation, median 1.6 U/ml; at clinical recovery, 1.2 U/ml). Crossed immunoelectrophoresis and sodium dodecyl sulphate-acrylamide electrophoresis with autoradiographic identification of multimeric structure revealed no evidence of structurally abnormal factor VIII-related antigen in diabetic ketoacidosis. However, an extra peak on crossed immunoelectrophoresis ("pre-peak") was a feature in the acute phase ketoacidotic plasma in six subjects, and may represent aggregated factor VIII. Changes in plasma factor VIII are a feature of diabetic ketoacidosis and, whilst not specific to this condition, may be the result of endothelial cell damage. PMID- 3108062 TI - [Aid to decision for nutritional support in chronic digestive diseases]. AB - In patients with chronic gastro-intestinal disease, deciding whether or not to provide nutritional support is difficult. The aim of the present study was to develop an objective index to help clinicians to decide which patients should be treated with nutritional support. Two hundred and two patients were studied prospectively. Seventy-one had an inflammatory bowel disease, 51, a malabsorption syndrome, 59, an esophagogastric disorder, and 21, a pancreatic disease. On admission, nutritional status was assessed by anthropometric and biological measurements, and spontaneous oral caloric intake. Clinical assessment of the nutritional condition was performed by an independent observer. Using discriminant analysis, collected data were correlated to the therapeutic outcome of the patient during the 15 days after admission, i. e. whether or not they received nutritional support. Clinical global assessment proved to be the most discriminant variable: 83 p. 100 of the patients were correctly classified. This variable was deleted from further analysis to obtain an objective index, calculated with four variables: mid-arm muscle circumference, body weight, serum albumin, and caloric oral intake expressed as kcal X IBW kg-1 X day-1. The index classified correctly 84 p. 100 of the patients. This study demonstrates that subjective clinical assessment is the best variable to decide whether or not a gastrointestinal patient should receive nutritional support. We suggest that this index might be of help in these situations. PMID- 3108063 TI - Percutaneous endoscopic gastrostomy. Indications, success, complications, and mortality in 314 consecutive patients. AB - The aim of this study was to determine the indications, success rate, procedure related mortality, and major and minor complication rates in 314 consecutive patients in whom we attempted a percutaneous endoscopic gastrostomy. The most common indications for placement of the gastrostomy tube were neurologic (n = 235, 75%) and oropharyngeal disorders (n = 42, 13%). We noted that the gastrostomy tube was successfully placed in 299 (95%) of the 314 patients. Ninety three percent (n = 291) of the patients had the procedure performed in the hospital and 7% (n = 23) were outpatients when the procedure was performed. In those patients with stable underlying conditions, the procedure can safely be performed in the outpatient setting. A low rate of procedure-related mortality (1%), major complication (3%), and minor complication (13%) was noted. Our experience suggests that the percutaneous endoscopic gastrostomy is safe and has a low mortality rate even in patients who are medically debilitated secondary to their underlying disease. PMID- 3108064 TI - Gastric acidification inhibits meal-stimulated gastric acid secretion after prostaglandin synthesis inhibition by indomethacin in humans. AB - The effects of cyclooxygenase inhibition by indomethacin on gastric acid secretion were studied in 8 healthy men. Oral doses of indomethacin (200 mg), administered 15 and 2 h before testing, were known to inhibit prostaglandin synthesis by 90% in 3 of the subjects as determined by prostaglandin E2 generation assay on endoscopically obtained gastric mucosal biopsy specimens. Acid-induced inhibition of gastric acid secretion was evaluated in a randomized and blinded study in which acid output was measured for 2 h during basal conditions by aspiration, for the next 2 h by intragastric titration during distention with isotonic glucose, and for the following 2 h by intragastric titration during meal stimulation with peptone. The studies were done on separate days, and intragastric pH was maintained at either 2.5 or 5.5 after administration of indomethacin or placebo. Basal acid output was not altered by indomethacin treatment. Distention of the stomach stimulated acid output significantly to a similar degree in all groups, without affecting plasma gastrin. Meal stimulation increased plasma gastrin and acid output significantly more at pH 5.5 (47 +/- 12 pM, 13 +/- 2 mmol/30 min) than at pH 2.5 (30 +/- 8 pM, 6 +/- 2 mmol/30 min). No effect of indomethacin treatment was observed. It is concluded that the participation of cyclooxygenase products in the mechanisms by which acid inhibits the gastric phase of acid secretion in humans is likely to be minor. These results also cast doubt on an important physiologic role for cyclooxygenase products in the regulation of basal acid secretion or of acid secretion stimulated by distention or a peptone meal. PMID- 3108066 TI - [Experience using preparations for parenteral feeding in the treatment of burns]. PMID- 3108065 TI - [Metabolic effects and general side effects in the treatment of endometriosis with an LHRH agonist]. AB - Between 1983 and 1986 40 patients were treated for external genital endometriosis with the LHRH agonist buserelin. Ovarian suppression was achieved for a period of six months with a dose of 900 to 1,800 mcg per day. In addition to gynecological findings, liver and kidney function and lipid metabolism were checked prior to treatment and at regular intervals during treatment. No deviations from normal ranges were found. The general side effects observed during treatment were as a rule attributable to the buserelin-induced relative estrogen deficiency. The efficacy of the medication in the treatment of endometriosis was demonstrated by control pelviscopy. Since no undesirable metabolic side effects have so far been observed with buserelin, it may be considered an effective new alternative treatment for endometriosis. PMID- 3108067 TI - Metabolism in sea raven (Hemitripterus americanus) hepatocytes: the effects of insulin and glucagon. AB - The metabolism of the sea raven, Hemitripterus americanus, hepatocyte preparation was studied, emphasizing the roles of insulin and glucagon on carbohydrate status. Sea raven hepatocyte glycogen was depleted throughout the preincubation and 2-hr incubation period in the presence of either glucose or serine. Bovine glucagon stimulated glycogen loss and increased glucose levels and serine flux to glucose. Porcine insulin prevented glycogen depletion at least over 1.5 hr of incubation, but did not affect glucose levels in the hepatocytes. It also significantly increased serine flux to glucose, glycogen, and protein, and alanine flux to glucose, CO2, and protein. Teleost insulin did not alter the pattern of hepatic glycogen depletion, while it did increase glucose levels and serine flux to glucose, glycogen, and lipids, and alanine flux to CO2 and glucose. Both glucagon and porcine insulin increased glucose flux to glycogen, but neither altered glucose conversion to CO2, lactate, or protein. The teleost insulin had no effect on glucose conversion to any product tested. Teleost insulin had an additive effect on the glucagon-induced increases in total glucose production and gluconeogenesis from serine, while glucagon offset the insulin stimulation of serine flux to glycogen and CO2. The results demonstrate that glucagon functions to increase glucose production from gluconeogenic precursors and glycogen in sea raven hepatocytes, while insulin demonstrates anabolic effects through gluconeogenic precursors. It is suggested that insulin functions in sea raven hepatocytes to increase glycogen stores through increased amino acid utilization and/or to increase glucose production for transport to, and storage in, glucose-utilizing tissues (e.g., muscle). An antagonism between insulin and glucagon on the glycolytic/gluconeogenic pathways as is found in mammalian livers is not as clear in sea raven hepatocytes. These findings are consistent with the carnivorous diet of the sea raven and a preferentially gluconeogenic role for the liver of this species. PMID- 3108068 TI - Effects of insulin-like growth factor I (IGF-I) on growth hormone-releasing factor (GRF) and thyrotropin-releasing hormone (TRH) stimulation of growth hormone (GH) secretion in the domestic fowl (Gallus domesticus). AB - Recent studies in mammalian species indicate that IGF-I may act as a negative feedback inhibitor of GH release through alteration of pituitary secretion or sensitivity to hypothalamic regulatory factors. Although avian GH secretion appears to be regulated by the differential release of hypothalamic inhibitory (somatostatin) and stimulatory (GRF and TRH) factors, feedback effects of IGF-I on in vivo GH release in birds have not been investigated. To study the effects of elevated IGF-I concentration on GRF- and TRH-stimulated GH secretion, 4-week old chickens received an intravenous injection of recombinant human IGF-I either 15 min prior to (6 micrograms, study 1), or simultaneous with (10 micrograms, study 2). GRF (hGRF44NH2, 5 micrograms/kg) or TRH (0.5 microgram/kg) administration. Radioimmunoassay analysis of plasma collected prior to and following peptide treatment indicated that circulating IGF-I concentrations were elevated 83.9, 60.6, 77.9, and 88.8% at the time of TRH and GRF administration in studies 1 and 2, respectively. Peak GH concentrations (mean of +5- and +15-min samples) subsequent to TRH injection were significantly (P less than 0.01) depressed 45.1 and 48.2% in IGF-I-treated as compared with control chicks in the first and second studies, respectively. GRF-stimulated GH secretion was significantly (P less than 0.01) decreased by IGF-I administration in study 2 (41.3%) but not in study 1. An estimated half-life for IGF-I in the chicken is less than 15 min based on the disappearance rate of the elevation produced by exogenous IGF-I injections. Thus, IGF-I exerts a negative feedback effect on pituitary hormone secretion in avian as well as mammalian species. PMID- 3108069 TI - Linkage and segregation analyses of apolipoproteins A1 and B, and lipoprotein cholesterol levels in a large pedigree with excess coronary heart disease: the Bogalusa Heart Study. AB - Robust methods were employed, using data from a single large pedigree, to screen serum apolipoprotein A1 and B levels, serum lipoprotein cholesterol levels, and ratios of serum lipoprotein cholesterol fractions to apolipoprotein A1 and B levels for genetic linkage to 31 polymorphic markers. Segregation analyses were performed for each of the apolipoprotein and lipoprotein cholesterol fractions to obtain estimates for use in applying likelihood methods of linkage analysis. Trait-marker combinations for which linkages were suggested from the robust methods were then reexamined for linkage using the likelihood (lod score) method. Results from the segregation analyses were consistent with major gene determination of apo B and HDL-C levels, the HDL-C to apo A1 ratio, the LDL-C to apo B ratio, and a measure of relative content of cholesterol in HDL-C and LDL-C. Linkage between haptoglobin and the HDL-C/apo A1 ratio was suggested, with a lod score of 1.72 at theta = 0.05. PMID- 3108070 TI - Major locus inheritance of apolipoprotein B in Utah pedigrees. AB - A major locus that determines levels of apolipoprotein B (apoB) was revealed by likelihood analysis on 331 members of 36 pedigrees. The major locus explained 43.2% of the observed variance, with the remainder attributed to random environmental factors. Estimated mean apoB levels (mg/dl) were 110.5 +/- 2.5, 141.9 +/- 4.4, and 208.1 +/- 11.5 for low homozygotes, heterozygotes, and high homozygotes, respectively. The corresponding genotypic frequencies were 0.718, 0.259, and 0.023. The apoB locus explained 13% and 14% of the variance in total and low-density-lipoprotein cholesterol levels, respectively. Persons with elevated apoB had normal to high levels of total serum cholesterol and triglyceride and low to normal levels of high-density lipoprotein and apolipoprotein A-I. Sixteen members of three of the pedigrees were heterozygous for familial hypercholesterolemia (FH). Their apoB levels were estimated as 35.72 +/- 7.16 mg/dl above the apoB genotypic means, assuming that the two loci act independently. Therefore, two major loci, the FH locus and the apoB locus, affect two levels, apoB and LDL cholesterol. PMID- 3108071 TI - Recalibration of the Pseudomonas aeruginosa strain PAO chromosome map in time units using high-frequency-of-recombination donors. AB - High-frequency-of-recombination donors of P. aeruginosa strain PAO were generated using a temperature-sensitive, replication mutant of the IncP-1 plasmid R68, loaded with the transposon Tn2521. Fourteen donors so isolated mobilized the chromosome in a polarized manner from a number of different transfer origins. The donors were used to construct a time of entry map of the entire chromosome and this was achieved by determining the time of entry of 32 randomly dispersed markers in crosses using nalidixic acid to interrupt chromosome transfer. Analysis of the time of entry data enabled the recalibration of the chromosome map to 75 min. PMID- 3108073 TI - Cytogenetics of Notch mutations arising in the unstable X chromosome Uc of Drosophila melanogaster. AB - A derivative of the unstable X chromosome, Uc, isolated in 1978 is still unstable and exhibits most of the genetic properties characteristic of the original Uc. This derivative, Df(1)cm-In, contains an inversion of the genes between bands 6F1 2 and 3D3-5 and a lethal deficiency between 6D5-7 and 6F1-2. This chromosome generated Notch mutations at a rate of 3.47 +/- 0.32% during seven consecutive generations. Cytological analysis of 50 Notch mutations of independent origin in the Df(1)cm-In chromosome showed that all of the 50 had an apparently identical deletion involving the region between 3D3-5 and 3C7-8 of the X chromosome. The results of in situ hybridization indicated that the extent of deletion in all of the 20 Notch deficiencies sampled from the 50 mentioned above involves about 10 kb of the sequences from the 3' end of the Notch locus. In addition to hypermutability and the accumulation of site-specific chromosome breaks, the Df(1)cm-In chromosome reinverts its inversion to the normal sequence and exhibits use of the existing chromosome breakpoints to generate new rearrangements. PMID- 3108072 TI - Post-translational control of alcohol dehydrogenase levels in Drosophila melanogaster. AB - A trans-acting regulatory gene that alters in vivo protein levels of alcohol dehydrogenase (ADH) has been mapped to a region of the third chromosome of Drosophila melanogaster. The gene has been found to affect the in vivo stability of ADH protein. It was not found to alter levels of total protein of two other enzymes assayed. The action of the gene over development and its possible mode of control are discussed. PMID- 3108074 TI - A cell marker system and mosaic patterns during early embryonic development in Drosophila melanogaster. AB - An embryonic cell marker system has been developed in Drosophila melanogaster that has enabled us to identify the genotype of cells as early as the cellular blastoderm stage of development. This system allows unambiguous detection of embryos homozygous for most X-linked lethal mutations at stages prior to when their first defects become obvious. By examining gynandromorphs at this stage, we have observed that the number of nuclei per unit area in male regions is about half that in female regions. An examination of early cleavage stage embryos whose DNA has been stained with Hoechst 33258 and whose actin has been stained with phalloidin suggests that this difference is due to a cell cycle delay in cells losing the ring-X. These experiments also demonstrate the existence of a mechanism which controls the timing of nuclear divisions in cycle 10-14 embryos. PMID- 3108076 TI - A cytogenetical study of 7-day-old bovine embryos of poor morphological quality. AB - Seven-day-old embryos were collected from Canadian Holstein and Ayrshire heifers after superovulation with pregnant mare's serum gonadotropin (PMSG) or follicle stimulating hormone (FSH). A total of 103 morphologically abnormal (type C) and 23 morphologically normal (type A) embryos were cytogenetically analyzed after 4, 20-24, or 44-48 h of culture in enriched phosphate-buffered saline or Eagles minimum essential medium. Twenty-one of 23 (91.3%) type A and 75 of 103 (72.8%) type C embryos had cells in metaphase. Among the 21 type C embryos produced by PMSG stimulation, 17 (80.9%) could be analyzed: 6 were mixoploid (two 2n/3n, three 2n/4n, one 2n/6n), 2 were aneuploid (61 XXY), and 9 were diploid. Among the 82 type C embryos produced by FSH stimulation, 58 (70.7%) could be analyzed: 6 were mixoploid (one n/2n, one 2n/3n, three 2n/4n, one 2n/4n/8n), 2 were polyploid (4n), and 50 were diploid. No abnormalities were observed in the type A embryos. PMID- 3108075 TI - The P-M hybrid dysgenesis cline in Eastern Australian Drosophila melanogaster: discrete P, Q and M regions are nearly contiguous. AB - The dramatic latitudinal cline in P-M hybrid dysgenesis characteristics along the east coast of Australia is not smooth. Tests of recent collections of Drosophila melanogaster from the southeastern coast define the previously described cline as comprising three discrete, apparently contiguous regions of P, Q and M phenotypes, respectively. Northern populations from Cairns (16.9 degrees SLat) to Ourimbah (33.4 degrees SLat) are phenotypically P; populations from Wollongong (34.4 degrees SLat) to Eden (37.1 degrees SLat) are Q; and populations from Genoa (37.5 degrees SLat) to Cygnet (43.2 degrees SLat) are M. The decline in P activity from northern Queensland (55-60% gonadal dysgenesis (GD) in cross A) to mid-New South Wales (20-30% GD in cross A) is gradual; proceeding south, there then is a sharp drop to Q populations (less than 10% GD in crosses A and A*). This drop in P activity occurs in only 150 km, across the urban and suburban area of Sydney. Q populations are then found south to Eden, but Genoa, only about 50 km further southeast, is clearly M (48% GD in cross A*), as are two populations further south. The two discontinuities in the P-M cline do not correspond to obvious climatic differences along the coast, nor to obvious barriers to dispersal of D. melanogaster. The cline has apparently not moved between 1983 and 1985-1986. PMID- 3108077 TI - The Donald P. Kent memorial lecture. Strategic planning: the catastrophic approach. PMID- 3108078 TI - Merit Gram: a form of recognition in a long-term care setting. PMID- 3108079 TI - Institutional care utilization by the elderly: a critical review. PMID- 3108080 TI - Ownership, regulation, quality assessment, and performance in the long-term health care industry. PMID- 3108081 TI - Do you need a computer? Can you afford a computer? Part II. Choosing a computer system that is cost effective. PMID- 3108082 TI - Maximizing RN potential in a long-term-care setting. PMID- 3108084 TI - Effect of the hormonal contraception on serum reverse triiodothyronine levels. AB - Thyroid hormones and the thyroxine-binding globulin are increased during hormonal treatment with oral contraceptives without changes in the thyroidal economy. Now we report that even reverse triiodothyronine, the main peripheral catabolite of thyroxine, is significantly increased during therapy with oral contraceptives. PMID- 3108083 TI - Study on the hyperresponsiveness of pituitary FSH to GnRH 6 weeks after delivery. AB - We investigated the mechanism underlying the hyperresponsiveness of pituitary FSH to GnRH stimulation in puerperal women 6 weeks after delivery. No pulse of LH during the 3-hour sampling period was observed in all of 4 puerperal women studied on day 42 postpartum, while each of 5 eumenorrheic women on day 8 or 9 of the normal cycle had one or two pulses of LH in the 3-hour sampling period. In puerperal women on day 42 postpartum, the mean basal level of serum FSH was slightly, but not significantly higher than that in eumenorrheic women on day 8 or 9 of the normal cycle, but the mean basal levels of serum LH and estradiol were significantly lower than those in eumenorrheic women. The response of serum FSH to GnRH stimulation was significantly and 2-fold higher in puerperal women on day 42 postpartum than in eumenorrheic women on day 8 or 9 of the normal cycle, but there was no difference in the response of serum LH to GnRH between the two groups. These results suggest that the hyperresponsiveness of pituitary FSH to GnRH stimulation in puerperal women on day 42 postpartum may result from the slower frequency of GnRH secretion. PMID- 3108085 TI - Decreased killer cell activity in preeclampsia. AB - Anti-D antibody-dependent cellular cytotoxicity of peripheral blood mononuclear cells was measured against O, Rh (D)-positive erythrocytes in 20 healthy pregnant women (chosen from all trimesters), and in 16 toxemic patients; it was then compared to the cytotoxic activities of 20 women 3 months after parturition and to that of 42 nonpregnant women. The application of an enzyme-like kinetic model for measurement of maximal cytotoxic function has permitted sensitive determination of the K cell function. It was found that during normal pregnancy maternal K cell activity did not change, whereas it was significantly decreased in preeclampsia. PMID- 3108087 TI - Leukapheresis in CLL. PMID- 3108086 TI - The molecular basis of cell reproduction; have we been looking in the wrong place? PMID- 3108088 TI - New prognostic factors in multiple myeloma. PMID- 3108089 TI - Cytochemical study of tetrahydrofolate dehydrogenase in myelodysplastic syndromes. PMID- 3108090 TI - Serum beta 2 microglobulin in multiple myeloma and related plasma cell dyscrasias. PMID- 3108091 TI - The disaggregation of Hodgkin's lymph node: a preparative technique using a new dissociation chamber. PMID- 3108092 TI - Chromosome studies in human hematologic diseases: non-Hodgkin's lymphomas. PMID- 3108093 TI - Surface phenotype and clinical stages in B-cell chronic lymphocytic leukaemia. PMID- 3108094 TI - Spontaneous deep haematomas in two patients with myelofibrosis. Evidence of platelet membrane glycoprotein modifications. PMID- 3108095 TI - Haematopoietic factors in haemodialysed patients. Epidemiologic study and therapeutic suggestions. PMID- 3108096 TI - DA-DAPI positive heterochromatin in the interphase nuclei of human white blood cells. PMID- 3108097 TI - Use of locally injected anti-T monoclonal antibodies in the treatment of acute corneal graft rejection. PMID- 3108099 TI - A case of Richter's syndrome due to the spontaneous proliferation of two immunologically unrelated B cell malignancies. PMID- 3108098 TI - Low-dose cytosine arabinoside (Ara-C) therapy in the myelodysplastic syndromes and acute myelogenous leukemia. PMID- 3108100 TI - Treatment of adult acute non-lymphoblastic leukemia: a computer-aided analysis. PMID- 3108101 TI - Endothelium, vessel injury and thrombosis. PMID- 3108102 TI - 4'-Deoxydoxorubicin (esorubicin) in non-Hodgkin's lymphomas and plasma cell tumors: first evidence of activity. PMID- 3108103 TI - Effect of insulin therapy on coagulation and platelet function in type II (non insulin-dependent) diabetes mellitus. AB - Twenty type II (non-insulin-dependent) poorly controlled diabetics had tests of coagulation and platelet function performed while receiving high-dose sulphonylurea therapy and at 1 and 3 months following their conversion to insulin. Although no overall change in glycaemic control (assessed by glycosylated haemoglobin) was noted, a reduction in thrombin generation was observed, as judged by a significant fall in fibrinopeptide A concentrations. No changes in factor VIII coagulant activity (VIII:C), factor VIII-related antigen or antithrombin III were found. Glycosylated haemoglobin concentrations showed significant correlations with antithrombin III and factor VIII:C, suggesting that improved glycaemic control might lead to an improvement of antithrombin III function and lower factor VIII:C concentrations. No changes in platelet function were detected. The introduction of an insulin regimen that improves glycaemic control might lead to a reversal of the 'hypercoagulable state' found in type II diabetes. PMID- 3108104 TI - Nonenzymatic glucosylation as a contributing factor to defective fibrinolysis in diabetes mellitus. AB - Kinetics of activation of plasminogen purified from the plasma of 3 uncontrolled diabetic patients by tissue type plasminogen activator revealed substrate inhibition in the fibrin-stimulated system. After improvement of metabolic parameters activation of plasminogen was found to be normal in 1 of these patients and partially improved in another patient. Studies performed to investigate a possible nonenzymatic glucosylation of plasminogen showed that purified control plasminogen incorporates 14C-glucose in a dose- and time dependent manner and that in vitro glucosylation of control plasminogen results in functional abnormalities of plasminogen, which resemble those observed with plasminogen from diabetic patients as far as substrate inhibition in the fibrin stimulated system is concerned. PMID- 3108105 TI - Neurophysiological variables and fibrinolysis in insulin-dependent diabetes treated with an aldose reductase inhibitor or placebo. A double-blind randomized study. AB - In a double-blind study we randomized insulin-dependent diabetics (n = 19) into a group (n = 12) given daily 250 mg Sorbinil, a potent aldose reductase inhibitor reported to ameliorate diabetic neuropathy, and another group (n = 7) given placebo for 1 year. Objective, neurophysiological variables (biothesiometry, electromyography, nyctometri) were followed throughout the study and correlated with fibrinolytic variables in blood. We found that Sorbinil did not improve any of the selected neurophysiological variables. Neither did Sorbinil induce marked changes in the fibrinolytic activities of the extrinsic, tissue-type plasminogen activator (t-PA), or in the intrinsic factor XII-dependent or factor XII independent (urokinase-like) plasminogen activator systems. We found no effect of Sorbinil on the activity of the fast-reacting inhibitor (PA-I) of plasminogen activator. Levels of PA-I in plasma influence the amounts of t-PA precipitated in euglobulins. PMID- 3108106 TI - A clinico-pathologoanatomical study of renal damage in patients with diabetes mellitus. PMID- 3108107 TI - On the question of polygenic type heredity in duodenal ulcer disease. PMID- 3108108 TI - X-ray therapy in degenerative-distrophic diseases of the bones and joints. PMID- 3108109 TI - Scintigraphic diagnosis of occult bone metastases in patients with operable breast cancer. PMID- 3108110 TI - The interdependence between maximum mean expiratory flow (MMEF25-75%) and some spirographic diffusion and blood-gas indices in patients with chronic non specific lung disease (CNLD). PMID- 3108111 TI - A study of the effect of the rotating magnetic field on erythrocytes acid resistance. PMID- 3108112 TI - Combination of fixed and removable prostheses in contemporary treatment of edentulous areas. PMID- 3108113 TI - A method of CT-examination of the lymphatic nodes in the maxillofacial and cervical regions. PMID- 3108114 TI - Electron microscope studies of the ulcer-surrounding mucosa in stomach ulcers. PMID- 3108115 TI - A method of casting and forming plaster working casts using metal boxing strips. PMID- 3108116 TI - Bacterial isolation from and transmission by Boophilus decoloratus and Boophilus geigyi. AB - Bacteria were isolated from the haemolymph of Boophilus decoloratus and Boophilus geigyi which had engorged on trade cattle in Nigeria. All the genera of the bacteria were also isolated from the eggs which they laid although some of them were missing from the larvae which eventually hatched. When clean rabbits were inoculated with some genera of bacteria and clean, laboratory bred larvae of B. decoloratus and B. geigyi fed on them, the same genera of bacteria were subsequently isolated from the haemolymph of the engorged adults, the eggs they produced and the larvae which hatched from them. Staphylococcus pyogenes and Pseudomonas aeruginosa were consistently encountered in the haemolymph, eggs and larvae of both Boophilus species while Proteus mirabilis was additionally consistent in B. geigyi. PMID- 3108117 TI - Geographic distribution of Bhanja virus. AB - A review on the geographic distribution, vectors and hosts of Bhanja virus (Bunyaviridae) is based on reports about: isolations of the virus; antibody surveys. Bhanja virus has been isolated in 15 countries of Asia, Africa and Europe, and antibodies against it have been detected in 15 additional countries. Vector range includes ticks of the family Ixodidae (subfam. Amblyomminae; not subfam. Ixodinae): 13 species of 6 genera (Haemaphysalis, Dermacentor, Hyalomma, Amblyomma, Rhipicephalus and Boophilus) yielded the virus. Bhanja virus has only rarely been isolated from vertebrates (Atelerix, Xerus, Ovis, Bos; possibly bats), though antibodies have been detected frequently in a wide range of mammals (Ruminantia being the major hosts), in several species of birds (Passeriformes, Galliformes) and even reptiles (Ophisaurus apodus). Natural foci of the Bhanja virus infections are of the boskematic type (sensu Rosicky), associated closely with pastures of domestic ruminants infested by ticks in the regions of tropical, subtropical and partly temperate climatic zones. PMID- 3108118 TI - Effect of various inducing agents on bacteriocin (klebocin) production by Klebsiella pneumoniae. AB - The influence of various inducing agents on growth, synthesis and release of klebocin by Klebsiella pneumoniae was studied. A significant level of klebocin was detected only after induction. The highest level of klebocin was achieved with mitomycin C followed by rifampicin and polymyxin B. Chloramphenicol and UV irradiation did not show any effect on klebocin production. Maximum klebocin release occurred after 8 h of induction with all the agents. Concentration of mitomycin C did not show any significant effect on klebocin production. PMID- 3108120 TI - Formation of extracellular neutral proteinase and the stringent response in Bacillus subtilis. AB - The kinetics of extracellular neutral proteinase synthesis by an isogenic stringent (IS58) and a relaxed (IS56) strain of B. subtilis were compared. The specific enzyme formation rate by the stringent strain was higher than that of the relaxed one. Norvaline addition (1 mg/mL) induced the formation of pppGpp and ppGpp, respectively, as well as the appearance of extracellular neutral proteinase activities in cultures of the stringent strain IS58 and a strain with high proteinase production (ZF-178) only. These correlations support the suggestion that (p)ppGpp are involved in the regulation processes responsible for production of extracellular neutral proteinases by B. subtilis. PMID- 3108119 TI - Factors influencing the activity of cellular alkaline phosphatase during growth and sporulation of Bacillus cereus. AB - Alkaline phosphatase (EC 3.1.3.1) is synthesized in media with a low phosphate concentration (0.37 mM of total and 19 microM of inorganic phosphate, respectively) already during the exponential phase of growth of Bacillus cereus. The enzyme is repressed by higher phosphate concentrations (3.7 mM) during the whole growth period; during sporogenesis the enzyme activity in cells slightly increases even under these conditions. During growth the enzyme is not secreted into the medium, a minor amount being released after cessation of growth. The enzyme activity can be increased by adding Zn2+ ions (10 microM). When during growth without phosphate the pH of the medium decreases below 5.0, the enzyme activity temporarily decreases and growth is slowed down, followed by a subsequent increase of the enzyme activity. In this case the onset of sporulation is also delayed. PMID- 3108121 TI - Estimation of australopithecine stature from long bones: A.L.288-1 as a test case. AB - Regression equations for the estimation of stature from long bones, although derived from modern human populations, are frequently applied to early hominids. In fact, some of these equations have even been recommended or especially created to be applied to Australopithecus remains. In this study, 45 sets of regression and correlation formulae, recurrent in anthropological and medico-legal literature, are applied to long bones of the Pliocene hominid A.L.288-1 ('Lucy'), in order to assess which, if any, could be considered suitable for stature reconstruction in 'gracile' australopithecines. Virtually every method based on regression equations overestimates stature as compared with the estimate based on reconstruction of all the preserved skeletal parts. In addition, most methods failed to give consistent results with data from different limb segments. None of the sets of regression formulae tested here can be recommended as a reliable means of stature estimation in 'gracile' australopithecines. PMID- 3108122 TI - New wrist bones of Proconsul africanus and P. nyanzae from Rusinga Island, Kenya. AB - The anatomy of the wrist of two species of the early Miocene hominoid Proconsul is described based on new material collected on Rusinga Island, Kenya. These fossils generally confirm previous findings that the wrist of Proconsul is monkey like in much of its morphology. However, the structure of the ulnar side of the wrist, particularly the ulnocarpal joint, is significantly different from that of extant monkeys and suggests some functional affinities with extant hominoids. Thus the wrist of Proconsul is neither monkey-like nor ape-like in its total morphology. Instead, it shows a unique combination of features which once again point to the oversimplicity of forcing fossil forms into categories based only on extant taxa. PMID- 3108124 TI - Induction of rat hepatic monooxygenase activity by polychlorinated diphenyl ethers. AB - Polychlorinated diphenyl ethers are recognized environmental contaminants. Twelve of these compounds were tested for their ability to induce liver cytochrome P-450 and monooxygenase activities in Sprague-Dawley rats. All the compounds increased P-450 levels or increased monooxygenase activities in a manner resembling 3 methylcholanthrene, phenobarbital or a combination of both (mixed). The responses obtained resembled those of the polychlorinated biphenyls, some of which are known to be toxic. PMID- 3108123 TI - Effect of dietary carbohydrate type and content on the response of male rats to dietary sodium saccharin. AB - The role of dietary carbohydrate composition and concentration in the response of male rats to sodium saccharin (NaS) was ascertained by comparing the response to 5% dietary NaS in rats given diets containing 65% starch, 50% sucrose together with 15% starch, 65% glucose, or 3% sucrose. NaS induced similar levels of caecal enlargement and increases in urine volume and bladder mass when given with any of the three forms of carbohydrate at 65% in the diet. However with the 3% sucrose diet, NaS caused a lesser caecal enlargement and no increase in urine volume or bladder mass. These findings suggest that NaS not only inhibits saccharide hydrolysis but also inhibits glucose transport. The significance of these findings in relation to NaS-associated bladder tumours is discussed. PMID- 3108125 TI - Occult malunion of ankle fractures--a cause of disability in the athlete. AB - Occult malunion of the ankle is a condition in which the talus appears to be situated in its normal position on standard radiographs. The lateral malleolus, however, is incompletely reduced. This causes a subluxation of the distal tibiofibular joint and some degree of talar instability. The malunion of the lateral malleolus is best visualized on lateral radiographs or tomograms. This condition can be corrected by osteotomizing the lateral malleolus and restoring the integrity of the distal tibiofibular joint by pulling the lateral malleolus distally and internally rotating it. PMID- 3108126 TI - [Peptic ulcer. New H2 blockers, prostaglandins, benzimidazoles]. PMID- 3108127 TI - [Electroencephalographic foci without structural diagnostic correlates]. AB - On account of the increasing availability of various new, computer-aided and non invasive imaging techniques it seems advisable to reconsider the structural diagnostic use of the EEG which is a functional-diagnostic instrument by its nature. On the level of visuo-morphologic description local and locally accentuated patterns can only be conceived as deformations of the temporo-spatial gestalt of the EEG. On the level of interpretation, i.e. in answering the question whether such patterns are indicative of a circumscribed structural lesion or not, further information is required. In addition to clinical data such information is provided by the electroencephalographic context. Typical arrangements of the EEG-context which make improbable an assumption of a structural lesion can be demonstrated for certain anterior-left as well as posterior-right localized patterns. From such regular co-incidencies, which are illustrated by paper chart examples, we conclude that these "foci" represent local manifestations of a global functional impairment. Whereas the intermittently occurring anterior-left accentuated slow wave patterns refer to an incipient global functional disintegration, the posterior-right accentuated slow wave patterns can be regarded as a reflection of a global functional deficit of maturation. A third phenomenal domain which persistently confronts us with the structural-diagnostic limitations of the EEG consists of the focal patterns in patients with epilepsy. It may be assumed that the pronounced lateral inconsistency of these focal patterns, occurring within the recording period and even more when comparing serial recordings, is dependent both on the actual (vigilance) and the relatively outlasting level of central nervous organization (maturation). PMID- 3108128 TI - The New Jersey DRG system: another view. PMID- 3108129 TI - Viable strategies for dealing with the uninsured. PMID- 3108130 TI - Calcitonin and hepatic fatty acid synthesis: effect of thyroparathyroidectomy on the elevation of ATP citrate lyase activity by refeeding of starved rats. AB - The effect of thyroparathyroidectomy (TPTX) on ATP citrate lyase regulation, a rate-limiting enzyme of fatty acid synthesis in hepatic cytosol, was investigated in rats refed after a 24 h fast. ATP citrate lyase activity in the hepatic cytosol was increased 2-fold by refeeding. This increase was suppressed about 50% by TPTX. The suppression of the enzyme activity by TPTX was completely restored by administration of calcitonin (CT; 80 MRC mU/100 g body weight). This hormonal effect was also observed at 20 MRC mU/100 g dose of CT. CT administration to refeeding-TPTX rats produced a significant increase in the calcium content of the liver tissue and the cytosol. The cytosolic ATP citrate lyase activity increase with CT administration was completely blocked by treatment of cytosol with EGTA (10 microM). This inhibition was clearly reversed by addition of calcium ion (1.25-5.0 microM). In addition, CT-induced rise in enzyme activity was markedly reduced by the presence of W-7 (5 and 50 microM), a calmodulin inhibitor, in the enzyme assay system. The present results suggest that CT plays a role in the elevation of hepatic ATP citrate lyase activity brought about by refeeding of fasted rats, and that this hormonal regulation might depend on Ca2+-calmodulin. PMID- 3108131 TI - Cardiovascular, catecholamine and psychological responses to TRH in four types of affective disorder patients. AB - When 500 micrograms of TRH is given intravenously, an increase in TSH, blood pressure, plasma catecholamines and positive emotions follows. Four groups of patients with major, minor or bipolar depression or schizoaffective disorder increased their TSH levels by similar amounts after TRH. The neurohormone also significantly increased diastolic blood pressure by 5.5 +/- 1.6 mm Hg, and decreased heart rate by 7.6 +/- 1.3 beats/min. There was a weak trend for bipolar depressives to have less cardiovascular response to TRH than the other groups. Plasma norepinephrine (NE) was higher after TRH than after placebo. The NE response differed between patient groups (P = .0023) because of a smaller response by major depressives. TRH decreased anger, tension and depression, and increased friendliness. Positive emotional responses were significantly greater in the bipolar depressives than in other groups. Forty-one other studies have found a subnormal TSH response does not distinguish between subtypes of the affective disorders, but cardiovascular, catecholamine and mood responses may do so. PMID- 3108132 TI - Changes in LH and FSH serum pattern following L-T4 withdrawal in L-T4 substituted hypothyroids. PMID- 3108133 TI - Metabolism of GnRH in man: influence of estrogens. AB - To clarify the influence of estrogens on the metabolism of gonadotropin-releasing hormone (GnRH), we studied the metabolic clearance rate (MCR) of GnRH (MCRGnRH), and the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and testosterone (total and free fraction) in 9 sexually mature men and 7 women under basal conditions and after treatment with the antiestrogen tamoxifen (2 X 10 mg/day p.o.) for 7 days. In women, the medication was started on day 7 +/- 1 of their menstrual cycles. To calculate the MCR, synthetic GnRH was continuously infused (1.53 micrograms/min) and its serum levels were measured by a radioimmunoassay. During tamoxifen treatment we observed a small but significant decrease in the MCR in men (455 +/- 48 to 357 +/- 46 ml/min/1.86 m2), whereas the known cyclic increase in the MCR in women was blunted (1,769 +/- 147 to 1,558 +/- 119 ml/min/1.86 m2). There was a small but significant increase in LH levels in women (8.3 +/- 2.1 to 11.5 +/- 2.5 mU/ml). LH and testosterone levels in men, and FSH and estradiol levels in both sexes did not change significantly. CONCLUSION: (1) estrogens regulate the MCRGnRH either directly or by changing gonadotropin levels, but the effect is only slight; (2) an enhanced metabolism of GnRH may contribute to the feedback of estrogens on the secretion of gonadotropins, and (3) the sex-specific difference of the MCR is presumably not caused by estrogens. PMID- 3108134 TI - TSH and PRL responses to domperidone and TRH in men with insulin-dependent diabetes mellitus of different duration. AB - The effect of domperidone, a specific blocker of dopamine receptors, on serum TSH and PRL levels was evaluated in 16 euthyroid men affected by insulin-dependent diabetes mellitus (IDDM) of different duration and in 7 age-matched normal controls. Diabetics were divided into 2 groups of 8 men according to the duration of their disease (group I: 1-9 years; group II: 11-18 years). Both groups had normal basal levels of TSH and PRL. Responses of these hormones to domperidone were similar in normal controls and in group I diabetics, whereas they were significantly reduced in patients of group II. When all 16 diabetics were studied together, a significant negative correlation was found between mean maximal peaks of TSH and PRL responses to domperidone and duration of diabetes. In order to evaluate whether the reduced effect of domperidone in diabetics was due to alterations of the dopaminergic control of TSH and PRL secretion, the domperidone test was repeated in 6 normal controls and in 6 diabetics of group II after infusion of dopamine (4 micrograms/kg/min for 2 h). Dopamine infusion induced parallel decreases in TSH and PRL concentrations, without modifying hormonal secretory patterns in response to domperidone. These data suggested that the reduced TSH and PRL responses to domperidone in diabetics were not due to alterations of the dopaminergic control of pituitary function but to a defect at the pituitary level. To test this hypothesis, TSH and PRL responses to TRH were evaluated in group I and group II diabetics and in normal controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108135 TI - Dopamine inhibits thyrotropin-releasing hormone release from rat adrenal gland in vitro. AB - The effects of dopamine on the release of thyrotropin-releasing hormone (TRH) from the rat adrenal gland were studied in vitro. The rat adrenal glands were incubated in medium 199 with 1.0 mg/ml of bacitracin and 100 micrograms/ml of ascorbic acid (pH 7.4) (medium) for 20 min. The amount of TRH release into the medium was measured by radioimmunoassay. The immunoreactive TRH (ir-TRH) release from the rat adrenal gland was inhibited significantly in a dose-related manner with the addition of dopamine and enhanced with the addition of pimozide or domperidone to the medium. Dopamine's effects on ir-TRH release from the adrenal gland were blocked with the addition of pimozide or domperidone. The elution profile of methanol-extracted rat adrenal gland was identical to that of synthetic TRH. The findings suggest that the dopaminergic system inhibits TRH release from the rat adrenal gland. PMID- 3108137 TI - Occupational exposures to chlorophenoxy herbicides. PMID- 3108136 TI - Western blot analysis of gonococcal serogrouping reagents. AB - The W class antisera used in the coagglutination method of serogrouping Neisseria gonorrhoeae were analysed using sodium dodecyl sulphate polyacrylamide gel electrophoresis and western blot transfers. All were found to contain antibodies to the homologous protein II as well as antibodies to protein I group antigens. Examination of local isolates showed that some strains owed their reaction with coagglutination reagents to epitopes on their protein II not their protein I. How this may lead to difficulties when using coagglutination patterns to subdivide the W groups is discussed. PMID- 3108138 TI - Lysine: arginine ratio of protein and its effect on cholesterol metabolism. PMID- 3108139 TI - A monoclonal antibody inhibiting leucocyte adhesion blocks induction of IL-2 production but not IL-2 receptor expression. AB - Monoclonal antibody 60.3 defines the leucocyte antigen CD 18 and recognizes a cell surface glycoprotein with an apparent molecular weight (MW) of 90,000 expressed by most human peripheral blood and bone marrow cells. This antibody can, among other things, block phorbol ester-induced adhesion among human mononuclear leucocytes. We show in this study that phorbol esters alone can induce peripheral blood mononuclear cells (PBL) to secrete interleukin-2 (IL-2) and that the IL-2-dependent cell line CTLL can be used for measuring this lymphokine without influence of the phorbol esters themselves. These findings make it possible to analyse the capacity of antibody 60.3 to interfere with IL-2 production and receptor expression by phorbol ester or phytohaemagglutinin (PHA) treated human PBL. A significant positive correlation between blockage of induced cell aggregation by antibody 60.3 and reduction in IL-2 release was observed. The addition of interleukin-1 (IL-1) restored IL-2 secretion in PHA-treated, but not in 4-beta-phorbol 12, 13-dibutyrate [P(Bu)2]-treated, cells in the presence of this antibody. In parallel, IL-2 receptor expression was determined by immunofluorescence using biotinylated anti-IL-2 receptor (Tac) antibodies. FACS analysis showed that IL-2 receptor expression was unaffected by antibody 60.3, whereas DNA synthesis of the same P(Bu)2-treated PBL was inhibited. However, addition of external recombinant IL-2 overcame this proliferation blockade. These results indicate that a cell-to-cell adhesion step is necessary for the production of IL-2, but not for the expression of its receptor on both PHA- and P(Bu)2-treated human PBL. PMID- 3108141 TI - Inhibitory mechanism of the proliferative response of B lymphocytes: suppression of the proliferation induced by anti-mu antibody and BSF1 by immune complexes. AB - We studied the effect of immune complexes (IC) on the responses of polyclonally activated murine B cells. For this, normal resting B cells were stimulated with the F(ab')2 fraction of goat anti-mouse mu-chain antibody and B-cell stimulating factor 1 (BSF1) after preculturing them with IC. Next, the relative membrane potential changes and the subsequent proliferative response were analysed. IC, particularly in antibody excess, inhibited both membrane depolarization and while those in antigen excess did poorly. Neither antigen nor antibody alone was effective. Inhibition was mediated via binding of IC to FcR gamma on B cells in a dose-dependent manner. Kinetic experiments showed that at least 6 hr was necessary for inducing the suppression of B-cell responses after binding of IC. We conclude that IC bound to FcR gamma on B cells regulates B-cell responses by acting on the initial step of activation. PMID- 3108140 TI - Biosynthesis and secretion of the third component of complement by human endothelial cells in vitro. AB - The third component of complement (C3) is synthesized and released by cultured human capillary endothelial cells. After the incubation of cells in a methionine free medium containing 35S-methionine for 48 hr, culture supernatants were immunoprecipitated with anti-human C3 serum. SDS solubilization and 2-ME reduction of the immunoprecipitates, followed by separation with SDS polyacrylamide gel electrophoresis and autoradiography, revealed two major bands comparable to those of the alpha and beta chains of human C3. The content of C3 in the culture medium harvested at different time-intervals was determined by ELISA. The C3 secretion rate was about 250 ng/10(6) cells/5 days in the primary culture medium and 75 ng/10(6) cells/5 days after seven passages. The capillary endothelial cells described here have factor VIIIRAg specific for endothelial cells, and exhibit ring formation resembling capillary lumina, but they lack Weibel-Palade bodies. PMID- 3108142 TI - Human cytotoxic T lymphocytes. II. Frequency analysis of cyclosporin A-sensitive alloreactive cytotoxic T-lymphocyte precursors. AB - A limiting dilution (LD) culture system was used to investigate the effect of cyclosporin A (CsA) on the activation and differentiation of human alloreactive cytotoxic T-lymphocyte precursors (CTL-p). CsA reduced in a dose-dependent fashion the frequency of alloantigen-inducible CTL-p. With most normal individuals tested there was a 20- to 50-fold reduction of alloreactive CTL-p frequencies in the presence of 500-1000 ng/ml CsA. Both unseparated T cells and CD8+ T cells were CsA-sensitive under LD culture conditions. Importantly, however, alloreactive CTL-p from two out of 21 normal individuals were found to be largely CsA-resistant. CsA did not affect the growth of MLR-primed CTL in secondary LD culture. Furthermore, CsA slightly inhibited the cytolytic activity of some alloantigen-specific CTL clones. These results are discussed with respect to the clinical use of CsA in transplantation medicine. PMID- 3108143 TI - Toad splenocytes bind human IL-2 and anti-human IL-2 receptor antibody specifically. AB - Human r-DNA IL-2 and fluorescent (Fl) mouse anti-human IL-2 receptor antibody have been tested separately and in competition with each other for their capacities to bind to the splenocytes of Xenopus laevis, the South African clawed toad. Binding by Fl*-mouse anti-DNP antibody of the same subclass (IgG1, kappa) was used as a control. The results of visual tests using rIL-2 coated fluorescent Covaspheres demonstrate that the human mediator will bind cells of the toad spleen. Moreover, the mediator inhibits binding of the antibody against the human IL-2 receptor, as detected by cytofluorimetry. Some of the IL-2 receptors on the toad cells appear to be constitutive, since they are expressed on freshly biopsied lymphocytes. Activation of these cells in vitro will increase the percentage of those cells able to bind both the anti-receptor antibody and rIL-2. Since the human mediator is only able to modulate in vivo immune activity in antigen-activated toads, it appears that in spite of having some constitutive IL 2 receptors, a quantitative increase in receptor expression is required before immunological behavior can be effected. More stringent controls of receptor expression may have provided an additional regulatory level as mammalian mechanisms evolved. PMID- 3108145 TI - Subpopulations of T lymphocytes. PMID- 3108144 TI - Clonal activation of cytotoxic lymphocyte precursors by monoclonal anti-CD3 antibody: analysis of feeder cell requirements. AB - Activation of cytotoxic lymphocyte precursors (CLP) by the mitogenic monoclonal anti-CD3 antibody OKT3 was studied under limiting dilution (LD) culture conditions. One out of 2-6 E-rosette-purified T cells gave rise to a cytotoxic T cell (CTL) clone when cultured in the presence of OKT3 (0.2-2 ng/ml), recombinant IL-2 (100 U/ml), and irradiated feeder cells. Clonal CLP activation was optimally supported by a combination of E-rosette-depleted non-T feeder cells with small numbers of T cells added back. Among the cell lines tested, Fc-receptor-bearing monocytic cell lines U937 and HL-60 were efficient feeder cells whereas T cell lines (Jurkat, Molt-4, Ke37) did not support clonal CLP activation. These data indicate that clonal activation of CLP and differentiation into cytotoxic effector cells under LD culture conditions are critically influenced by the type and number of feeder cells used. PMID- 3108147 TI - Precocious disjunction of XY-bivalent in mouse germinal cells exposed in vivo to mitomycin C. PMID- 3108146 TI - IFN-gamma is not an essential mediator of murine antibody responses in vitro. AB - We have used purified murine gamma-interferon (Mu IFN-gamma) and anti-Mu IFN gamma monoclonal antibody to study the participation of gamma-interferon (IFN gamma) in in vitro plaque-forming cell (PFC) responses to antigen. We have studied several supernatants with T-cell replacing factor (TRF) activity as well as helper T-cell dependent anti-sheep red blood cells (SRBC) PFC responses. Our findings demonstrate that neither TRF- nor T-cell mediated responses are critically dependent upon IFN-gamma. PMID- 3108149 TI - Radiobiology of Bacillus megaterium spores: physicochemical events involving oxygen and caffeine. PMID- 3108148 TI - Modulation of macrophage activity by microorganisms. PMID- 3108150 TI - Temperature induced changes in brush border lactase and alkaline phosphatase activities of developing rat intestine. PMID- 3108151 TI - Effect of Nosema algerae vavra and undeen spores infection on longevity and fecundity of larval instars of Aedes aegypti L. and Culex fatigans Weid. PMID- 3108153 TI - In vitro antibiotic susceptibility pattern of Neisseria gonorrhoeae isolated at Pune. PMID- 3108152 TI - Protease & elastase production & their association with aeruginocine & pigment production by clinical isolates of Pseudomonas aeruginosa. PMID- 3108154 TI - Nutritional status of preschool children in a backward community. PMID- 3108155 TI - New experimental approaches to reducing carcinogenicity in animals by modifying regimens. PMID- 3108156 TI - Prevention of urotoxic side effects by regional detoxification with increased selectivity of oxazaphosphorine cytostatics. AB - Urotoxic side effects, particularly haemorrhagic cystitis, have been a limiting factor for the therapeutic use of the oxazaphosphorine cytostatics cyclophosphamide, ifosfamide and trofosfamide. The development of mesna (Uromitexan) has made it possible to carry out regional detoxification in the kidneys and the efferent urinary tract and thus to achieve clinically prophylaxis against the urotoxic side effects of oxazaphosphorines. In the body, mesna is rapidly converted to the biologically inactive disulfide form (dimesna). After glomerular filtration, dimesna is reduced by interaction with the glutathione system of the renal tubular cells and is excreted in the urine as mesna, the free thiol compound. This compound is then capable of definitively detoxifying the oxazaphosphorine metabolites in the urine. In extensive experiments on rats, it has been demonstrated that the cyclophosphamide-induced occurrence of urinary bladder tumours could be reduced or even eliminated by simultaneous administration of mesna. Detoxification by mesna enables the clinical use of higher doses and, consequently, a possible increase in therapeutic efficiency. PMID- 3108157 TI - Arachidonic acid-induced inflammation: inhibition by dual inhibitor of arachidonic acid metabolism, SK&F 86002. AB - The antiinflammatory activity of the structurally novel dual inhibitor of arachidonic acid metabolism, SK&F 86002 was evaluated using arachidonic acid induced edema and inflammatory cell infiltration. Histological examination demonstrated extensive subcutaneous edema and neutrophil (PMN) accumulation in perivascular and interstitial locations one hour after application of arachidonic acid to the ear. SK&F 86002 and, to a lesser extent, phenidone demonstrated potent inhibition of this inflammatory response following oral and topical administration. Nordihydroguaiaretic acid (NDGA) displayed only topical activity. The selective cyclooxygenase inhibitors ibuprofen and naproxen were either inactive or stimulated ear swelling. Histological evaluation of the lesion in drug-treated animals revealed that SK&F 86002 impaired edema formation and caused a significant reduction in numbers of infiltrating neutrophils. Using arachidonic acid-induced peritoneal exudation, a reduction in the cellular infiltrate was observed after oral treatment with SK&F 86002 or phenidone, but not with naproxen. Taken together, these data illustrate the potent antiinflammatory effects of SK&F 86002 and support the suggestion that 5-lipoxygenase products play a significant role in both the edematous and cellular phases of arachidonic acid-induced inflammation. PMID- 3108158 TI - Effect of acute inflammation on rat apolipoprotein mRNA levels. AB - Hybridization studies using specific cDNA have been used to determine the mRNA levels for rat apolipoproteins AI, AII, AIV, and E in extracts of rat liver and intestine. The ratios of intestinal mRNA/liver mRNA for apolipoprotein AI (apo AI), apo AIV, and apo E were 1.3, 1.7, and 0.1, respectively. Apo AII mRNA was detected in the liver but not in the intestine. The mRNA levels for apo AII and apo AIV in rat liver decreased during inflammation to minimums of 40% and 25% of normal, respectively. The mRNA levels for apo AIV in the intestine, apo E in the liver and for apo AI in both the liver and intestine did not change significantly during inflammation. The time course for the decrease in the hepatic mRNA levels for apo AIV was similar to those previously observed for the negative acute-phase proteins albumin and transthyretin. The serum levels for apo AIV were not affected by inflammation. PMID- 3108159 TI - [Effect of lipid emulsions on nitrogen balance within the scope of perioperative parenteral feeding regimens]. AB - Patients with colorectal cancer were parenterally fed before and after surgery by two different isocaloric regimens: One group was infused with high carbohydrate solutions (carbohydrate group), the other group with carbohydrate in combination with fat emulsions (fat group). The daily dose of fat was restricted to 1 g fat/kg BW/day. These conditions led to the following results: No significant changes in the protein balance were observed between the patients of the two regimens. The protein sparing effect and the synthesis of short living proteins were comparable. The infused fat emulsions were utilized without metabolic complications. Patients in the fat group were adequately supplied with essential fatty acids which was documented by the higher level of linolic acid in the blood. The biochemical and histological analysis of the liver samples which were excised on occasion of surgery gave comparable triglyceride content in both groups. In the fat group little lipid deposition was seen in the parenchymal cells but lipid droplets were observed in the reticuloendothelial system (v. Kupffer cells). Thus, distribution of fat droplets is different in the 2 groups. Unfortunately analysis of lipid depositions in the liver at the end of the parenteral nutrition could not be performed. PMID- 3108161 TI - [6th joint annual meeting: German Society for Artificial Nutrition and the Austrian Society for Clinical Nutrition. Augsburg, 26-29 March 1987. Abstracts]. PMID- 3108160 TI - [Experiences with MCT containing fat emulsions in premature and newborn infants]. AB - Total parenteral nutrition (TPN) was given for 8-9 days to 15 prematures and full term neonates (gestational age 26-40 weeks) with respiratory problems or respiratory distress syndrome (RDS). The solutions were administered via peripheral veins during 24 h. Serum electrolytes, calcium, triglycerides and amino acids were measured before and on the 2nd, 4th and 7th day of TPN acid-base balance, blood glucose and serum bilirubin were measured daily and serum transaminases and total protein on the final day of TPN. The total amount of findings administered was 126 ml/kg BW/day and consisted of 10.4 g glucose, 1.9 g fat and 1.95 g amino acids with the total amount of calories reaching an average of 68.7 kcal/kg BW/day (61% glucose, 27.6% fat and 11.4% protein). Three children (2 very small prematures, 1 with severe perinatal asphyxia) died of causes unrelated to TPN. Serum electrolytes, calcium and blood glucose levels were in the normal range in all cases, acid-base balance was affected minimally and moderate hyperbilirubinemia was observed in all neonates. Serum transaminase values were in the normal range as was total protein. Hypertriglyceridemia with values over 3 mmol/l was observed in the very premature neonates and in one neonate with septicemia. Our findings are in favor of administration of MCT fat emulsion to prematures and full term neonates. PMID- 3108162 TI - Penetration in vitro of human and ferret dentine by three bacterial species in relation to their potential role in pulpal inflammation. PMID- 3108163 TI - Influence of xid on anti-azophenylarsonate (Ar) antibody responses of (CBA/N x A/J)F1 mice: differential idiotype expression induced by only one of two Ar antigens. AB - The influence of an X chromosome-linked immune deficiency gene (xid) on several properties of the anti-azophenylarsonate (Ar) antibody responses of (CBA/N x A/J)F1 (NAF1) mice was examined. With respect to response magnitude, it was found that male, xid-expressing NAF1 mice showed about 1/3 the concentration of serum anti-Ar antibody as normal female NAF1 mice in hyperimmune responses to Brucella abortus (BA)-Ar. In responses induced by keyhole limpet hemocyanin (KLH)-Ar, males showed responses of about 1/8 to 1/2 the female levels, depending on the assay time point. The kinetics of the latter response were identical in mice of the two sexes. No significant difference could be detected in the time-dependent avidity maturation of the anti-Ar antibody elicited by KLH-Ar in xid vs. normal mice. The isotype profile of the day 38 anti-Ar primary response elicited by KLH Ar in male NAF1 mice differed from that of the female mice in two ways: IgG2a levels were depressed, and a significantly lower number of the male mice demonstrated detectable IgG3 anti-Ar antibody production. The primary focus of htis work was to determine the effect of xid on the expression of the major cross reactive idiotype--CRIA--of A strain mice. It was found that while a significant higher proportion of the female mice could be classified as high CRIA producers in responses to BA-Ar, no difference could be demonstrated if the inducing antigen was KLH-Ar. It is proposed that the difference observed with the two antigens may be due to the more selective activation by KLH-Ar of a small subset of high affinity Ar-specific clones--which may be enriched for CRIA + precursors- in both normal and immune defective mice. In contrast, BA-Ar may 'sample' more of the total anti-Ar repertoire and thus reveal within it an xid-determined depression in the proportion of CRIA + clones. Finally, it is noted that the influence of xid appears to be largely of a stochastic, and not an absolute character. PMID- 3108165 TI - Induction of antiphosphocholine antibodies utilizing lambda light chains in BALB/c mice. AB - BALB/c mice immunized with 1 or 100 micrograms of phosphocholine (PC)-keyhole limpet hemocyanin absorbed on aluminum hydroxide gel (alum) produced up to 50% lambda 1-light-chain-containing anti-PC antibodies in their serum. Only 10% lambda 1 antibodies were seen when complete Freund's adjuvant or bentonite were used as the adjuvant or if PC-bovine serum albumin was used with alum. Thus, the induction of large lambda-antibody responses to PC (a response usually dominated by kappa-antibodies) was both adjuvant- and carrier-dependent. PMID- 3108166 TI - Reactivity of two major allergens isolated from Schistosoma japonicum eggs against IgE and IgG antibodies in human serum. AB - Antigenicity and specificity of two major allergens termed J1 and J2, both of which had been purified from soluble egg antigen (SEA) preparation of Schistosoma japonicum, were examined against serum from schistosomiasis japonica patients. By using enzyme-linked immunosorbent assay, specific IgE or IgG levels to J1 or J2 in the patients' sera correlated well with those to crude SEA, indicating that J1 and J2 are the major antigens in SEA binding human IgE and IgG antibodies. Binding inhibition studies using 125I-J1 and 125I-J2 clearly showed that cross reactivity was not present between J1 and J2 in terms of their capacity to bind IgG or IgE antibody. When antibody levels of an individual patient to these two purified antigens were compared, a high degree of correlation was observed between them, regardless of the class of antibody. However, specific IgE antibody levels of individual serum to J1 or J2 were not correlated with IgG antibody levels to the respective antigen. PMID- 3108164 TI - Interleukin-2 responses of MRL/lpr mouse splenocytes and lymph node cells induced by TPA and A23187. AB - Treatment of splenocytes and lymph node cells of 5 month-old MRL/lpr mice with TPA induced IL-2-dependent proliferation of the cells in the presence of CA++. The induced response was inhibited completely by a monoclonal antibody to IL-2 receptor. The combination of TPA and A23187 in the lpr cells induced both proliferation and production of IL-2 in a Ca++-dependent fashion. The proliferative response of the lpr cells was equivalent to that of congenic (MRL/+/+) or normal cells, but the quantity of IL-2 secreted from the lpr cells was significantly less than that of the controls. Actinomycin D, but not mitomycin C, blocked IL-2 secretion from the treated lpr cells indicating de novo synthesis of IL-2 mRNA in the cells. Thus the lpr lymphocytes can be activated to proliferate in response to IL-2, yet they do not secrete IL-2 at a normal level even if activation signals are transmitted into the cells. PMID- 3108167 TI - Melanoma cell lysis by human CTL clones: differential involvement of T3, T8 and HLA antigens. AB - Three lymphocyte clones, derived by micromanipulation from peripheral blood lymphocytes (PBL) of a melanoma patient and expressing a broad pattern of reactivity against different target cells, were analyzed for the involvement of T cell markers and HLA antigens in the lysis of target cells by blocking experiments with a panel of monoclonal antibodies (MAbs). The clones lysed autologous melanoma cells (Me 28) and 18 out of 22 allogeneic targets including neoplastic and normal cells of different histological origin. Anti-T3 and anti-T8 MAbs strongly inhibited the cytotoxicity of the lymphocyte clones against Me 28, 3 allogeneic melanomas and 3 carcinomas, but failed to affect the lysis of K562. Anti-HLA class-I MAb (w6/32) produced a significant enhancement of the lysis of Me 28 by the 3 clones without modifying cytotoxicity against one allogeneic melanoma or against K562 cells. Anti-HLA class-II MAb (D1.12) did not affect the lysis of the same targets by the 3 clones. These results thus indicate that some anti-melanoma CTL clones may interact with autologous tumor cells by the T3 and T8 structures in an HLA class-I unrestricted manner. PMID- 3108168 TI - Glycoproteic nature of surface molecules of effector cells with lymphokine activated killer (LAK) activity. Evidence that T11, T8 or T3 molecules are not involved in tumor-cell lysis by LAK effector T cells. AB - Human peripheral blood mononuclear cells cultured in the presence of interleukin 2 (IL-2) acquire the capability of lysing NK-resistant fresh tumor target cells. In an attempt to delineate the surface structure(s) present on the effector cells, the latter were first treated with different amounts of pronase and neuraminidase. The effect of the enzymes on cytolytic activity against fresh melanoma cells was evaluated and compared with the NK-like activity against K562 target cells of the same effector population. At a pronase concentration of 0.01 mg/ml, no inhibition of NK-like activity was detected, whereas LAK activity was inhibited by more than 75%. In addition, neuraminidase had no effect on NK-like activity, even at 1 U/ml, whereas as little as 0.03 U/ml inhibited LAK activity by more than 75%. Metabolic inhibition of N-linked glycosylation with Tunicamycin prevented the generation of LAK activity, even when added late (18 hr before termination of the culture). Tunicamycin, on the other hand, had no effect on the boost of NK activity induced by IL-2. Provided that LAK activity can also be generated in T-cell (E-rosetting) populations, in the presence of adherent cells, we analyzed the inhibitory activity of monoclonal antibodies (MAbs) to T11, T3 and T8 molecules. While all these MAbs strongly inhibited the specific target cell lysis by alloreactive CTLs, they had no effect on the LAK activity. PMID- 3108169 TI - Prompt relief of vasospastic angina by calcium antagonists. AB - A 57-year-old man had recurrent episodes of angina pectoris at rest. An electrocardiogram (ECG) during attack revealed transient ST elevations in leads V1 to V5. His symptoms were not relieved by sublingual nitroglycerin (TNG), but subsided promptly following sublingual or intravenous calcium antagonists. However, there was no difference between the degree of ST elevation on ECG recorded during the treatment of angina with either TNG or with calcium antagonist. Recurrent angina and painless ST elevation on Holter ECG recordings were prevented by a large dose of diltiazem. Coronary arteriography revealed only mild stenosis at the proximal portion of the left anterior descending coronary artery. It is suggested that coronary artery spasm was the cause of angina in this case and that sublingual or intravenous calcium antagonist was more effective in the treatment of acute attack of vasospastic angina than sublingual TNG. PMID- 3108170 TI - Influence of short-term lithium carbonate administration on stimulated insulin secretion in normal man. AB - We have studied the effects of short-term treatment with lithium carbonate (900 1,200 mg/day for 4 days) on insulin secretion and blood glucose levels of 28 healthy volunteers (8 females and 20 males, aged 23-29 years) who underwent the following stimulations: two intravenous glucose loads of 25 and 5 g (IVGTT25; IVGTT5); arginine infusion (25 g over 30 min); tolbutamide test (0.25 g i.v.). Seven subjects for each group were tested. A placebo treatment was also performed. Short-term lithium treatment significantly reduced the insulin response to IVGTT25, arginine and tolbutamide. No differences were observed in blood glucose levels during all stimuli. Serum electrolyte levels and thyroid function were not affected by the treatment. In conclusion, these findings suggest, in healthy subjects, a good peripheral glucose utilization after brief term lithium administration, in spite of impaired insulin response to various stimuli. PMID- 3108172 TI - Drug-concentration dependent sensitivity to lysis by antibody and complement, of adriamycin- or mitomycin-treated murine lymphoma cells. AB - Murine lymphoma cells (RDM4) were pretreated in culture, with Adriamycin (ADM) and with Mitomycin C (Mit C), at different concentrations, for 20 h and carefully washed. In a first series of experiments, they were labelled with 51Cr and used as target to the lytic action of alloantiserum and complement (Ab + c), as appraised by the specific 51Cr release test. It was found that exposures of the prospective target cells to high drug concentrations (e.g. 32 micrograms/ml of ADM or 20 micrograms/ml of Mit C) enhanced their susceptibility to Ab + c killing, whereas exposures to low concentrations (i.e. 0.1 microgram/ml of ADM, or 1 microgram/ml of Mit C) protected them from Ab + c mediated lysis. In a second experimental series, similarly treated RDM4 were pulsed with 3H-TdR after their exposure to Ab + c. In this case, the cytotoxic effect was appraised as "inhibition" of isotope incorporation. Using this second criterion, the protective action of pretreatment with low drug concentrations was confirmed, and was particularly clearcut in the case of ADM. The protective effect of pretreatment with low concentration of ADM (0.1 microgram) was also confirmed in vivo, with the "Winn assay". PMID- 3108171 TI - Serotonin S2 receptors blockage and generalized anxiety disorders. A double-blind study on ritanserin and lorazepam. AB - Serotonin (5-HT) and 5-HT receptors are involved in mood disturbances, such as anxiety and depression. Ritanserin is a new substance with highly selective blocking activity on S2 receptors for 5-HT in the central nervous system. Ritanserin, (20 mg daily) and lorazepam (5 mg daily) were administered to 24 patients suffering from generalized anxiety disorders (DSM III), in a double blind fashion for six weeks. The results obtained showed comparable improvement in almost all patients with both drugs. Future studies should pay particular attention to psychosomatic disturbances, depressed mood and dysthymic-like disorders, in which ritanserin seems to be more efficacious, according to the best responding items of the general anxiety check list used. PMID- 3108173 TI - Male unemployment and cause-specific mortality in postwar Scotland. AB - This article reports a time-series analysis of male unemployment and mortality in postwar Scotland. The results provide little evidence to support the hypothesis that unemployment exerts a significant and consistent positive impact on mortality from all causes, lung cancer, ischemic heart disease, and cerebrovascular disease. Although significant positive associations between unemployment and mortality from lung cancer and ischemic heart disease were detected for older males in the short term, the long-term association between unemployment and mortality tends to be negative. Further progress on establishing possible causal relationships between unemployment and health requires both the collaboration of medical and social scientists and a well designed prospective study that avoids many of the problems associated with time-series and cross sectional analyses. PMID- 3108174 TI - Relationships between training volume, physical performance capacity, and serum hormone concentrations during prolonged training in elite weight lifters. AB - A follow-up study of 1 year was performed on 11 male elite weight lifters. Several parameters including training volume, weight lifting performance, and serum hormone concentrations were measured during seven test occasions. In addition, the same measurements were repeated three times during a 6-week period preceding the primary competition, which took place about 5 months after beginning of the follow-up. The primary findings were observed during the 6-week period from which the first 2 weeks of stressful training was associated with significant decreases (P less than 0.01-0.001) in serum testosterone concentration, in testosterone/cortisol and in testosterone/SHBG ratios, and with a significant (P less than 0.001) increase in serum LH concentration. The individual changes during the stressful training in serum testosterone/SHBG ratio were related (r = .63; P less than 0.05) to the individual changes in the weight lifting result in the clean and jerk lift. During the following "normal" 2-week and reduced 2-week training periods, the concentration of serum testosterone remained unaltered, but serum cortisol and serum LH decreased significantly (P less than 0.05-0.01). During these periods, the serum testosterone/SHBG ratio increased (P less than 0.01). The individual changes during this preparatory 4 week training before the primary competition in serum testosterone/SHBG ratio and the individual changes in the weight lifting result in the clean and jerk lift correlated significantly with each other (r = .68; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108175 TI - Interactions between parasites and their hosts: metabolic aspects. PMID- 3108176 TI - Recent advances in human protozoan parasites of the gastrointestinal tract. PMID- 3108177 TI - Selection of the host for resistance: genetic control of protective immunity to schistosomes. PMID- 3108178 TI - Solving parasite-related problems in cultured crustacea. PMID- 3108179 TI - The regulation of trematode populations by density-dependent processes. PMID- 3108180 TI - Control of non-vector-borne protozoa. PMID- 3108182 TI - High performance liquid chromatographic determination of riboflavin in food--a comparison with a microbiological method. AB - The riboflavin content of commercial products of different origin was determined by reversed phase liquid chromatography. The method was compared with a standard microbiological assay with Lactobacillus casei. A comparison between the two methods gave a correlation coefficient of 0.9996 for vitamin enriched foods, dairy and health-food products. For these products the LC-method is well adapted for use in routine work. The results obtained from unenriched flours and flours with a high rate of extraction showed significantly lower values for the LC method. The sensitivity for the LC-method is good with a minimum detectable quantity of 50 pg. PMID- 3108181 TI - Lipid and retinol contents in the milk of Egyptian mothers with normal and sick infants. AB - Mature breast milk was collected from Egyptian lactating mothers (N = 35) and was analyzed for its lipid, retinol and carotene contents. Mean values of 3.78 +/- 0.3%, 29.5 +/- 4.92 micrograms/100 g and 65.2 +/- 16.28 micrograms/100 g were obtained for lipid, retinol and carotene in the milk of mothers with normal infants. The milk of mothers with sick infants was inferior in its quality with respect to the lipid and retinol contents. Milk retinol level correlated significantly with the growth of the normal infants. PMID- 3108183 TI - The effect of bilateral adrenalectomy on metabolism and tissue distribution of ascorbic acid in the rat. AB - Adult, male, Sprague-Dawley rats were injected with [1-14C] -ascorbic acid 11 days post bilateral adrenalectomy or sham-adrenalectomy, and immediately placed in metabolism chambers. Excreta (CO2 and urine) were collected for 48 hours. The animals were then sacrificed and 10 tissues were processed and assayed for total ascorbic acid (AA) and radioactivity. There was no significant difference in weight gain between groups post-operation. Adrenalectomized rats excreted significantly less radioactivity, resulting in a significantly longer estimated half-life of AA (173 +/- 7 h) than the sham-adrenalectomized controls (141 +/- 7 h). Weights of tissues were similar between groups. The concentration of AA was significantly higher (43%) in the heart and lower (17%) in the liver in adrenalectomized animals. This group of animals also had significantly higher levels of radioactivity in the heart (51%), kidney, and spleen (19%). The specific activity of AA (% dose/mg AA) was not different between groups for any tissue examined. These results demonstrate that adrenalectomy affects the degradation of AA and its concentration in selected tissues, with a profound effect on the heart. PMID- 3108184 TI - Evaluation of the EDTA-washed diet for use in the experimental production of zinc deficiency in human subjects. AB - Ethylenediaminetetraacetate (EDTA) is known to bind zinc (Zn) and other metals. EDTA-washed soy protein-based diet has been extensively used as a dietary model for the production of Zn-deficiency in human subjects as well as in experimental animals. The present study was conducted to test this diet for possible contamination with EDTA (inhereted by washing procedure) and also to evaluate it for its acceptability and palatibility by human subjects. In the first experiment, EDTA-washed soy protein-based diets were prepared as previously described (repeated washing with EDTA-sodium salt followed by washing with deionized water and filteration), but 14C-EDTA was used. Scintillation counter analysis showed no traces of 14C in the prepared diet (100% of the 14C activity was recovered in the filtrate). In the second experiment, the diets were prepared using inactive EDTA, then fed to 10 volunteers for sensory evaluation. Results of this trial showed that the palatibility and acceptability of these diets are generally very poor. In conclusion, the use of EDTA-washing procedure did not result in any contamination of the soy assay protein with the EDTA. However, the present dietary model may not be used to induce zinc deficiency in human volunteers on a long term basis since the palatibility of the washed product is poor. PMID- 3108185 TI - [Resuscitation of a 36-year-old patient with a short PQ time and a history of Hodgkin's disease]. PMID- 3108186 TI - Role of metabolism in effects of diflubenzuron on growth of B16 melanomas in mice. AB - The insect growth regulator diflubenzuron (DFB), which also inhibits growth of experimental tumors in mice, was studied to determine the influence of in vivo microsomal metabolism on its antitumor activity. DFB inhibits chitin synthesis and growth of imaginal epidermis in insects and suppresses melanogenesis and uptake of nucleosides in mouse melanoma cells, but the means of cell growth regulation and the role of metabolism of DFB in such regulation have not been established. Five daily injections of DFB (total of 4000 mg/kg) into C57BL/6 mice with B16 melanomas induced an acute 11-20% decrease in tumor volume and a 2-3 day increase in the initial tumor volume doubling time (Td), but at mid-treatment tumors regained maximum (control-like) rate of volume increase. Tumors in mice conditioned with a mixed function oxidase inhibitor (CoCl2) and treated with DFB did not decrease in mean volume, but their rate of volume increase was reduced by about 75% and the Td was increased by 4.2 days. In contrast, induction of mixed function oxidase with 3-methylcholanthrene (3-MC) or beta-napthaflavone (B-NF) enhanced the effects of DFB by a factor of 1.5 to 2.0. Therefore, aromatic hydroxylation of DFB may be required for tumor growth regulation. Three metabolites of DFB--two hydroxylated forms and a scission product, 4 chlorophenylurea (CPU), were also tested for tumor growth regulation. CPU was ineffective; a form oxidized at the 3 carbon of the phenyl ring (3-OH-DFB) was only marginally effective; but the 2-carbon form (2-OH-DFB) induced a 24% decrease in mean tumor volume and a 2.4 day increase in Td. Pretreatment with 3 MC and treatment with 2-OH-DFB also resulted in a 24% decrease in tumor volume and a 2.2 day increase in Td, but also reduced tumor volume increase to 20% between the 5th and 10th days after the initial 2-OH-DFB injection, compared to a 125% increase without 3-MC. Further, 3-MC pretreatment caused the otherwise marginally effective 3-OH-DFB to become almost as effective as 2-OH-DFB. These data support our previous report that DFB alters tumor growth and show that mixed function oxidase enhances effects of DFB, 2-OH-DFB and 3-OH-DFB. PMID- 3108187 TI - Heterogeneous survival responses of human gastric cancer clones to alpha difluoromethylornithine in vitro. AB - The effects of alpha Difluoromethylornithine (DFMO)2 on survival of human gastric cancer clones were studied in vitro. The responses were dose and time dependent. Treatments which lasted for less than 12 h were cytotoxic at only the highest doses used. The greatest effects on survival were observed only when cells were treated for 48 and 72 h. The effects on the clones produced by such prolonged treatment durations were heterogeneous, with survival values differing by as much as 460%. By contrast, the clonal survival responses to short DFMO treatments (12 h) were very uniform (dose differential of only 19%); however, this uniformity in response could be achieved only by using non-pharmacological doses of DFMO. The heterogeneity in survival responses in the clones might be slightly associated with their levels of intracellular spermidine. Clones with the smallest amounts of intracellular spermidine at the start of treatment were most sensitive to DFMO. However, this association may not hold up with further testing in other gastric cancer clones or when studied in other cancer lines in vitro. PMID- 3108188 TI - Cell cycle kinetics responses of human stomach cancer cells to reduction in polyamine levels by treatment with alpha difluoromethylornithine in vitro. AB - Treatment of human gastric cancer clones in vitro with low doses of DFMO (5 mM) produced elongation of the cell population doubling times and lowering of the saturation densities. By contrast, DFMO treatment of normal human skin fibroblasts altered only the saturation density. The lack of an effect of 5 mM DFMO on the doubling time of normal fibroblasts may be directly related to baseline intracellular putrescine levels, which were about 2.5 times higher than in the cancer cells. The same dose of DFMO caused a rapid decrease in intracellular polyamine levels in the tumor clones. The effects on the doubling time and saturation density were almost totally abolished by the addition of 50 microM putrescine to the growth medium during the first 24 h of treatment with DFMO. Exposure to 5 mM DFMO for 24 h caused the human gastric cancer cells to become blocked in G1 phase only, and this led to a reduction in the fraction of cells in S phase. The G1 block was reversible and this cohort of cells eventually passed through S phase and then through G2 and M. A higher 100 mM dose of DFMO and longer exposure times for both doses produced cell cycle changes and death of more than 90% of the cell population. These data suggest that cell kinetics changes observed under these experimental conditions may reflect polyamine related alterations in the biochemical events of cell cycle progression kinetics; but may also be the result of DFMO-induced loss of cell viability. PMID- 3108189 TI - Cause and prevention of mafosfamide-induced venous pain. AB - An experimental rat model for the study of venous pain induced by 4-hydroxy cyclophosphamide (4-OH-CP) derivatives was developed and validated. Using various metabolites and chemical variants of 4-OH-CP it was found that pain induction was independent from the compound's alkylating activity but possibly related to the spontaneous generation of minute amounts of acrolein from the 4-OH-CP molecule. Accordingly, the pain could be prevented by the addition of thiol compounds such as mesna or N-acetyl-cysteine. PMID- 3108191 TI - The uses of LH-releasing hormone and analogs in infertility. PMID- 3108190 TI - Recombinant gamma interferon in advanced breast cancer: a phase II trial. AB - Fifteen patients with advanced carcinoma of the breast who had failed prior chemotherapy, were treated with recombinant gamma interferon at a dose of 2mg/m2 (1mg = 2.4 X 10(7) international units) intravenously for five consecutive days every other week. The median patient age was 51 and all patients had a performance status of 0-2 (Karnofsky greater than or equal to 50). Thirteen patients had two or three sites of metastatic disease and seven were estrogen receptor positive. No complete or partial responses were noted. Although some patients had brief periods of stable disease, almost all patients progressed after one or two courses. Only one patient was able to receive six courses of induction therapy and a brief course of maintenance. Flu-like symptoms and nausea were seen in all patients; vomiting and anorexia were frequent. Hepatic toxicity manifested by enzyme elevation was common and was most severe in patients with liver metastases. In this study a highly purified biologically active gamma interferon was not associated with anti-tumor activity in previously treated women with metastatic breast cancer. PMID- 3108192 TI - Lipoxygenase isozymes in higher plants: biochemical properties and physiological role. PMID- 3108193 TI - Normal thyrotropin-releasing hormone responsiveness in thyrotoxic Graves' disease. PMID- 3108194 TI - Clinicians or committees--who should cut costs? PMID- 3108195 TI - The community blood supply and patients' choice. The community: still the best source of blood. PMID- 3108196 TI - Anti-thymocyte globulin therapy of hematologic disorders. PMID- 3108197 TI - Determining hospital product mix: an exploratory analysis. AB - Using an index to measure the scope and complexity of services provided by a hospital is an effective way to explore the relationship between the extent of a hospital's programs and its annual cost of operation. Ways to use the index to support a hospital's program development are presented. PMID- 3108198 TI - Update on tube-feeding formulas. PMID- 3108200 TI - Efficient radiolabeling of mammalian cells using 111In-tagged liposomes. AB - When indium-111 oxine labeled neutral liposomes were incubated with Chinese hamster V79 cells in the presence of 100 mM calcium, the cell-associated radioactivity increased approximately 75-fold over that observed in the absence of calcium. This is considerably higher (approximately 20 times) than the cellular uptake obtained when these cells are incubated in the presence of 111In oxine alone. The highest uptake of radioactivity occurred when no bovine serum albumin was present in the medium, while as little as 0.001% of the protein greatly reduced the cell-liposome association. These efficient cell labeling conditions were not found to affect the survival of the cells. PMID- 3108199 TI - Characterization of the uptake of 16 alpha-([18F]fluoro)-17 beta-estradiol in DMBA-induced mammary tumors. AB - In order to investigate possible correlations between the uptake of 16 alpha ([18F]fluoro)-17 beta-estradiol (18F-ES) by 7,12-dimethylbenz(a) anthracene (DMBA)-induced tumors in rats and the estrogen receptor (ER) content of these tumors, a comprehensive study was performed in which the tissue distribution of 18F-ES was measured in tumor-bearing rats, together with simultaneous measurements of blood volume (by technetium-labeled red blood cells) and blood flow (by iodoantipyrine infusion). In addition, the time course of 18F-ES metabolism and the tissue distribution of the metabolites was studied. Metabolism of 18F-ES is very rapid, and after 2 h, most of the activity in blood and nontarget tissues is due to metabolites; target tissue activity, however, is due mainly to unmetabolized compound. Most of the circulating activity, both 18F-ES and its metabolites, is strongly associated with macromolecules or cells, and while the metabolites are not taken up selectively by target tissues, they do enter nontarget tissues. Tumor blood volume and blood flow vary widely, but not in a way that appears related to tumor necrosis. The uptake of 18F-ES by the uterus and DMBA-induced mammary tumors of adult rats reaches maximum levels (ca 0.35 and 0.10% I.D./g X kg, respectively) at early times (0-1 h), and drops slowly thereafter. The uterus to nontarget or tumour to nontarget tissue ratios, however, start low and continue to increase, reaching maximum levels (ca 20 and 15, respectively) at 2-3 h. There does not, however, appear to be a simple relationship between tumor uptake (either as % I.D./g X kg or tumor to nontarget ratio) measured at a single 3 h time point and tumor ER content, even considering differences in tumor blood flow. This suggests that an estimation of tumor ER content will require the application of more complex pharmacodynamic models that involve the measurement of the complete profile of receptor lignad uptake, retention, and washout from target to nontarget areas. The application of such models will be assisted by the development of estrogen receptor binding ligands that are not converted to circulating metabolites. PMID- 3108201 TI - Hb E-Saskatoon or alpha 2 beta 2(22)(B4)Glu----Lys in a Spanish family. PMID- 3108202 TI - A new case of Hb Dagestan [alpha 60(E9)Lys----Glu]. PMID- 3108203 TI - [Mucopolysaccharidosis IV-A (Maroteaux-Lamy disease, severe form): incipient compressive myelopathy, cerebrospinal fluid fistula and tracheal stenosis in an adult patient]. AB - A 25-year-old male with the severe form of Maroteaux-Lamy disease (mucopolysaccharidosis VI-A) developed rhinoliquorrhea of undetermined origin. The head was held permanently in extension, and there was both inspiratory and expiratory stridor. Flexion of the head worsened the stridor and caused dyspnea. Radiological examination showed a massive narrowing of the trachea and a marked retropharyngeal and retrotracheal swelling. Hyperreflexia and slight impairment of the sensation of the lower limbs were found on neurological examination. Computed tomography revealed hydrocephalus and extreme narrowing of the subarachnoid space in the region of the occipito-cervical junction, caused by marked epidural soft tissue thickening and a dysplastic arch of the atlas protruding dorsally into the foramen magnum, and displacement of the cervical spinal cord. At the age of 26 years rhinoliquorrhea suddenly stopped and the patient developed acute signs of occlusive hydrocephalus. Emergency ventriculo peritoneal shunting was performed. PMID- 3108204 TI - A new fixed cryosection technique for the simultaneous immunocytochemical demonstration of T6 and S100 antigens. AB - A formalin-calcium fixation method of preparing cryosections is described, which allows demonstration of Langerhans' cells by S100 antigen staining on frozen sections. The number of Langerhans' cells given by T6 antigen staining is also higher in formalin-calcium fixed frozen sections than acetone fixed frozen sections. The preparation is suitable for dual demonstration of the two antigens on the same section enabling a more accurate numerical evaluation of Langerhans' cell populations in the normal cervical epithelium. PMID- 3108205 TI - Tube feeding enteral nutritional support in patients receiving radiation therapy for advanced head and neck cancer. AB - A retrospective study evaluated the role of tube feeding enteral nutritional support in patients receiving radiation therapy (RT) for Stage III and IV squamous cell carcinoma of the head and neck. Tube feeding (TF) by either nasogastric, cervical esophagostomy, or gastrostomy route was based on individual physician preference and patient acceptance. TF feeding starting before and continuing through RT (planned TF) was completed in 17 patients, whereas 9 patients did not receive TF until they lost weight during RT (interventional TF). No tube feeding was performed in 63 patients. By the end of RT, the planned TF group lost an average of 4.8% of initial body weight, compared to 7.1% in the no TF group and 9.4% in the interventional TF group. At the end of RT, only 6% of the planned TF group had lost over 10% of initial body weight, compared to 24% of the no TF group and 44% of the interventional group. Excluding patients who continued to lose weight after the end of RT due to rapidly recurrent tumor, 49% of the no TF group had a post-RT nadir weight loss over 10% of initial body weight, compared to 0% of the planned RT group. However, failure to receive the full RT dose and/or lengthy rest periods during RT were just as likely to occur in the planned TF group as in the no TF group. This retrospective review also could not demonstrate improved survival in the planned TF group. Complications, including peptic ulcer disease, aspiration pneumonia, cervical stoma abscess, and hepatic encephalopathy, occurred in 7 of the 26 patients (27%) receiving either planned or interventional TF. We conclude that TF will help minimize weight loss due to side effects of RT for head and neck cancer, particularly when TF is instituted before the onset of significant weight loss due to RT side effects. Survival differences, however, were not apparent. PMID- 3108206 TI - Benefits and costs of a control program for an epizootic of Staphylococcus aureus mastitis. AB - In response to an epizootic of Staphylococcus aureus mastitis, the owner of a 2,000-cow dairy instituted a treatment, prevention, and control program (hereafter, "intervention program") consisting of teat dipping, bacteriologic culturing of milk from all fresh cows and from cows with clinical signs of infection, and culling cows found to be infected. The program was highly beneficial, yielding $2.40 in direct benefits for every $1 invested. PMID- 3108207 TI - Multiple myeloma associated with the heavy chains of immunoglobulin A in a dog. AB - On the basis of microscopic evaluation of bone marrow aspirate, multiple myeloma and secondary marrow hypoplasia was diagnosed in a 7-year-old female Doberman Pinscher. Electrophoresis, radial gel diffusion, and immunoaffinity chromatography indicated that serum and urine specimens contained alpha immunoglobulins without kappa or lambda light chains. Whole immunoglobulins (Ig) A, IgG, or IgM were not found. The dog was treated with prednisolone and melphalan for 11 weeks, after which time the owner refused examination and treatment of the dog. PMID- 3108208 TI - Metabolic activation and covalent binding to nucleic acids of carcinogenic heterocyclic amines from cooked foods and amino acid pyrolysates. PMID- 3108210 TI - Induction of forestomach lesions in rats by oral administrations of naturally occurring antioxidants for 4 weeks. AB - The effects of naturally occurring antioxidants on rat forestomach epithelium were compared with those of synthetic antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), of which the former is a known forestomach carcinogen. Groups of five F344 male rats were given diet containing BHA, BHT, gallic acid, syringic acid, sesamol, caffeic acid, chlorogenic acid, ferulic acid, eugenol or esculin for 4 weeks at a level of 0.7% for BHT or 2% for other compounds. Histological examination of the forestomach showed that BHA induced hyperplasia mainly in the prefundic region near the esophageal orifice, caffeic acid induced pronounced hyperplasia throughout the forestomach epithelium, and sesamol induced large ulcers and hyperplasia in the central region. Thus, these naturally occurring antioxidants showed different toxicities and abilities to induce hyperplasia in the rat forestomach. PMID- 3108209 TI - Enhancing effects of N-ethyl-N'-nitro-N-nitrosoguanidine and sodium taurocholate on development of pepsinogen 1 decreased pyloric glands in rats initiated with N methyl-N'-nitro-N-nitrosoguanidine. AB - Sequential quantitative analyses were made of pepsinogen 1 (Pg 1) decreased pyloric glands after treating male WKY rats first with N-methyl-N'-nitro-N nitrosoguanidine (MNNG) and then with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) as a second gastric carcinogen or sodium taurocholate (Na-TC) as a gastric promoter. Animals received a single dose of MNNG (160 mg/kg body weight) by gastric intubation followed two weeks later by either ENNG in drinking water (100 micrograms/ml) (group 1), basal diet containing 0.25% Na-TC (group 2), or basal diet and tap water (group 3), from weeks 3 to 24. Animals were sacrificed at weeks 8, 12, 16, 20 and 24. Sections of the pyloric mucosa were investigated for Pg 1 immunostaining. In comparison with group 3, induction of Pg 1 decreased pyloric glands was significantly enhanced by ENNG from week 8 and by Na-TC from week 16. The former exerted a significantly stronger effect at each time point. The results suggest that Pg 1 decreased pyloric glands represent a good marker for early detection of gastric carcinogens and promoters in in vivo test systems. PMID- 3108211 TI - A transforming gene, hst, found in NIH 3T3 cells transformed with DNA from three stomach cancers and a colon cancer. AB - DNA samples from 5 out of 15 stomach cancers and from 5 out of 15 colon cancers showed transforming activity in NIH 3T3 cells upon transfection. A transforming gene from an NIH 3T3 transformant induced by transfection of DNA from a stomach cancer was cloned, and showed transforming activity amounting to 120 focus forming units/micrograms. The transforming gene was identified as hst. The hst gene was also responsible for acquisition of the transforming activity in DNA samples from 2 other stomach cancers and one colon cancer. PMID- 3108213 TI - Early change of adenosine triphosphate levels in L5178Y cells during hyperthermia. AB - The time course of the change of cellular ATP level was studied in L5178Y cells exposed continuously to various temperatures and compared with that of cell death determined by means of a dye-exclusion test. The ATP level first increased at all temperatures tested and then decreased at temperatures higher than 42 degrees. The onset of this decrease always preceded the beginning of cell death. The results support the idea that the cellular lethality of heat treatment is well correlated with cellular ATP content in L5178Y cells. PMID- 3108212 TI - Antitumor activity of erbstatin, a tyrosine protein kinase inhibitor. AB - A tyrosine protein kinase inhibitor, erbstatin, showed no antineoplastic effect on L-1210 mouse leukemia when it was injected alone. Erbstatin was found to be inactivated by incubation in serum, but not in dialyzed serum. It was also inactivated in reconstituted serum containing dialyzed serum components and ferric or ferrous ion. Because erbstatin was considered to be inactivated by the ferric or ferrous ion in serum, foroxymithine, which is a potent chelator for the ferric ion, was given to the mice together with erbstatin. Administration of both erbstatin and foroxymithine showed antineoplastic activity against L-1210 leukemia. PMID- 3108214 TI - The long-term prognosis of patients gastrectomized for benign gastroduodenal diseases. AB - To study the long-term prognosis after gastrectomy, a total of 6,662 gastrectomized patients who had been operated on for benign gastroduodenal diseases between 1965 and 1980 were followed up from September 1, 1984 to May 30, 1986. The final vital status for the observed period could not be confirmed in 493 patients (7.4%), giving a follow-up rate of 92.6%. The average observation period was 13.1 years. The mortality from total deaths was almost identical to that of the general population adjusted for sex, age, and time trends of mortality, except for lower mortality among males in the first five years after operation. The risk of cancer mortality at all sites was lower than that of the general population, mainly due to the lower mortality from stomach cancer. This trend was not affected either by the type of gastroduodenal disease or by the method of operation. However, lung cancer mortality among males was significantly higher and one of the reasons for that could be excess smoking by males. PMID- 3108215 TI - Relationship between westernization of dietary habits and mortality from breast and ovarian cancers in Japan. AB - To clarify the relationship between the westernization of dietary habits and the changes of mortality from breast and ovarian cancers in Japan, correlation analyses were performed using data from the Vital Statistics and National Nutritional Survey Reports. With increasing population size of the areas, the age adjusted death rates (AADRs) for both types of cancer increased together with the per capita intakes of fat, animal protein and western-style foods such as butter & margarine, cheese, ham & sausage and dairy products. The association of the AADRs with the population size was strong after the age group of 45-54 years in breast cancer, and became stronger as the age increased in ovarian cancer. The association of the AADRs with western-style foods was also observed in the correlation analyses among the 12 geographical districts in Japan. From chronological correlation analyses, the correlation coefficients for some nutrients and foods in breast cancer were highest when the "time-lag" between the foods/nutrients intake and the cancer mortality was assumed to be around 10 years. The results of the present study suggest that an increase of western-style fat-rich foods such as butter & margarine, cheese, bread and ham & sausage among Japanese might be associated with the recent increase of AADRs for breast cancer and ovarian cancers in Japan. PMID- 3108216 TI - Relationship between the duration of treatment and the incidence of renal cell tumors in male F344 rats administered potassium bromate. AB - In order to ascertain the minimum induction time, minimum treatment period and total dose required for development of renal cell tumors, KBrO3 at a concentration of 500 ppm was administered in the drinking water to a total of 232 male F344 rats divided into 14 experimental groups and the development of tumors was examined by two different approaches. In a continued-treatment study, administration of KBrO3 was stopped at week 13, 26, 39, 52 or 104 and rats were immediately sacrificed for comparison with controls given distilled water (DW) alone. Renal cell adenomas were found as early as after 26 weeks of treatment with KBrO3. The yields of dysplastic foci, adenomas and adenocarcinomas of the kidney, follicular cell tumors of the thyroid and mesotheliomas of the peritoneum increased with treatment, the final incidences all being statistically significant after administration of KBrO3 for 104 weeks. To examine the effect of discontinued treatment, on the other hand, the rats were given KBrO3 for the first 13, 26, 39 or 52 weeks and were subsequently maintained on DW alone until sacrifice at week 104. The incidences of tumors in these groups were compared with that of a group continuously administered KBrO3 for 104 weeks. The yields of renal dysplastic foci, adenomas and adenocarcinomas in all discontinued-treatment groups were approximately equal to or even higher than those in the group given KBrO3 continuously for 104 weeks. It is concluded that, under the conditions of this study: the minimum induction time for the development of renal adenomas was 26 weeks and the minimum treatment period and total dose for the induction of renal adenomas and adenocarcinomas were 13 weeks and 4 g/kg, respectively, when the rats were maintained thereafter on DW for 2 years. PMID- 3108217 TI - The involvement of chromosome 13 in the X-ray-induced in vitro transformation of mouse m5S cells. AB - The transformation of an immortalized but nonmalignant near-diploid mouse cell line (m5S) by X-ray irradiation was studied, and the chromosome constitutions of the morphologically transformed foci were analyzed. The frequency of transformation increased in a dose-dependent manner. Chromosome analysis revealed that 17 out of 24 transformants showed a common chromosome change, being characterized by a diminution of the C2-ter region of chromosome 13 as compared with the chromosome constitution of the parental untransformed cells. In these transformants, the diminution of 13(C2-ter) was critical in forming transformed foci, but was not sufficient to engender anchorage independence and tumorigenicity. The agar clonability and tumorigenicity were associated with the further appearance of an extra chromosomal segment seen as an abnormally banded region, probably consisting of tandem repeats of actively functioning genes. This experimental system thus revealed the progressive multistep nature of neoplastic transformation initiated by a loss of suppressive function. PMID- 3108218 TI - Urinary metabolites of N-nitrosodibutylamine and N-nitrodibutylamine in the rat: identification of N-acetyl-S-alkyl-L-cysteines. AB - N-Acetyl-S-butyl-L-cysteine, N-acetyl-S-3-oxobutyl-L-cysteine and N-acetyl-S-3 hydroxybutyl-L-cysteine have been isolated and identified (as their methyl esters) from the urine of rats given N-nitrosodibutylamine (NDBA), N nitrodibutylamine (NO2DBA) and their 1-acetoxy derivatives. Greater amounts of these N-acetyl-S-alkyl-L-cysteines were detected in the urine after administration of NDBA than of NO2DBA, and greater urinary excretion of the three N-acetyl-S-alkyl-L-cysteines was observed with 1-acetoxy NDBA than with 1-acetoxy NO2DBA. This suggests that the markedly different biological activities of NDBA and NO2DBA might be due, in part, to a difference in their alkylating abilities in vivo. PMID- 3108219 TI - Kinetic analysis of active efflux of vincristine from multidrug-resistant P388 leukemia cells. AB - Kinetic analysis of vincristine transport in parental and multidrug-resistant P388 leukemia cells was attempted by indirect assessment of its efflux. Practically, the initial velocity and steady-state level of vincristine uptake by ATP-depleted cells, and its steady-state level in untreated cells, were measured. As a result, a saturable process of not only influx but also efflux of vincristine was observed for the first time with both cell lines, suggesting the existence of a carrier-mediated system for influx and efflux. With increasing extracellular drug concentrations, the contribution of the mediated transport to the total flux was decreased and that of the unsaturable process, that is, simple diffusion, was increased. It should be particularly noted that the Km and Vmax values of efflux in the resistant cells were significantly less and greater, respectively, than those of the sensitive cells, providing a biochemical basis for enhanced efflux as a mechanism of multidrug-resistance. No significant difference in kinetic parameters of vincristine influx and intracellular binding contributing to resistance was found between the two cell lines. PMID- 3108220 TI - Enhanced anticancer efficacy by use of mitomycin C adsorbed on small activated carbon particles in mice. AB - A new dosage form of mitomycin C (MMC-CH) was tested for toxicity and therapeutic efficacy against intraperitoneally inoculated cancer cells in mice. MMC-CH is a suspension comprising 7.16 mg/ml of activated carbon particles, 1 mg/ml of mitomycin C (MMC) and 20 mg/ml of polyvinylpyrrolidone in saline. The LD50 value determined by means of the Litchfield-Wilcoxon method after intraperitoneal administration was 2.29 times higher for MMC-CH than for MMC aqueous solution. Mice were inoculated intraperitoneally with 2 X 10(5) P388 leukemia cells and given an intraperitoneal injection of 10 to 1.25 mg/kg of MMC in the form of MMC CH or MMC aqueous solution 24 hr after the inoculation. The median survival time was prolonged to 270.5%, 223.0% or 168.3% by MMC-CH at the dose equivalent to 10, 5 or 2.5 mg/kg of MMC, respectively, while it was prolonged to 182.7%, 139.6% or 155.4% by MMC aqueous solution at the dose of 5, 2.5 or 1.25 mg/kg of MMC, respectively, as compared with the median survival time in the non-treated group. MMC-CH prolonged the survival time to more than 120% as compared with the same dose of MMC given as MMC aqueous solution, and was less toxic. PMID- 3108221 TI - The antitumor potency of oral tegafur against adenocarcinoma 755 in mice is markedly enhanced by oral (E)-5-(2-bromovinyl)-2'-deoxyuridine. AB - A significant inhibition of the growth of adenocarcinoma 755 tumors in BDF1 mice was effected by oral tegafur (FT) in combination with oral (E)-5-(2-bromovinyl) 2'-deoxyuridine (BVdUrd), at doses at which neither drug used alone had antitumor activity. The maximum inhibition of tumor growth (97%) was achieved by using a combination of 50 mg FT/kg with 10 mg BVdUrd/kg but, even at a dose as low as 1 mg BVdUrd/kg, the antitumor potency of FT was enhanced. The effect which BVdUrd has on the antitumor potency of FT is apparently due to inhibitory action by bromovinyluracil, the phosphorolytic product of BVdUrd, on the degradation of 5 fluorouracil, the oxidative product of FT, by dihydrothymine dehydrogenase. PMID- 3108222 TI - Evidence for a role of cyclooxygenase (prostaglandin synthetase) and prostaglandins in the sperm acrosome reaction and fertilization. AB - Three cyclooxygenase (prostaglandin synthetase) inhibitors, indomethacin, phenylbutazone, and oxyphenbutazone, decreased fertilization in vitro when mixed with capacitated mouse spermatozoa before addition of the treated gametes to oocytes. Fertilization was inhibited whether the oocytes were intact, follicle cell-free, or both follicle cell-free and zona-free. At various concentrations of inhibitor, no effect was observed on the motility or forward progression of the spermatozoa. These cyclooxygenase inhibitors also decreased the guinea pig acrosome reaction. Inhibition of the acrosome reaction did not occur when a mixture of the prostaglandins (PGE2 or PGF2 alpha) and one of the inhibitors was added to the spermatozoa. Alone, these prostaglandins tended to enhance the rate at which the acrosome reaction took place. Lowered calcium levels reduced the occurrence of the acrosome reaction, an effect that could be reversed at least partially by the addition of PGE2. Even in the nominal absence of calcium, some acrosome reaction took place when PGE2 was present in the medium. These results support an essential role for cyclooxygenase and arachidonic acid metabolites, including prostaglandins, in the events leading to the acrosome reaction and fertilization. PMID- 3108223 TI - Follicle stimulating hormone, luteinizing hormone and testicular Leydig cell responses to estradiol immunization in Ile-de-France rams. AB - Active immunization of Ile-de-France rams against estradiol (E2) resulted in the production of E2-neutralizing antibodies and an elevation in the plasma concentrations of FSH, LH, and testosterone. The presence of E2 antibodies did not affect the testosterone metabolic clearance rate, indicating that the immunization-mediated 10-fold increase in plasma testosterone was the result of a 10-fold increase in testicular testosterone production. Testis weights, as well as nuclear and cytoplasmic volumes of individual peritubular and perivascular Leydig cells, were greater in E2-immunized rams than in albumin-immunized controls. Leydig cell numbers were not affected by treatment. The E2 antibodies were capable not only of neutralizing the inhibitory effects of endogenous E2 on gonadotropin levels in intact rams, but were able to block the effects of exogenously administered E2 on their FSH and LH secretory response to castration. It is concluded that circulating E2 in the ram is involved in pituitary testicular endocrine homeostasis and that E2 immunoneutralization can be employed to enhance testosterone secretion in this species. PMID- 3108224 TI - The structure of inducing factors for virginiamycin production in Streptomyces virginiae. AB - Virginiamycin inducing factors (inducing material or inducing factor) of Streptomyces virginiae were isolated from the culture broth of this microbe and separated into three closely related compounds. They were named virginiae butanolides A, B and C and their structures were determined as 2-(1'-hydroxy-5' methylhexyl)-3-(hydroxymethyl)butanolide (6), 2-(1'-hydroxy-4'-methylhexyl)-3 (hydroxymethyl)butanolide (7) and 2-(1'-hydroxyhexyl)-3-(hydroxymethyl)butanolide (8), respectively. Part of their stereochemistry was also determined. Racemic virginiae butanolide C was synthesized to confirm their structures. PMID- 3108225 TI - Cochlear blood flow in the rat. A methodological evaluation of the microsphere method. AB - With the microsphere method it is possible to quantify the blood flow in various organs. The blood flow in the cochlea is only a very small part of the cardiac output and only relatively few microspheres are caught in this organ, which necessitates large groups of animals for such studies. The method has, however, not been fully evaluated for studies of small organs in small animals. In this study, 130 rats of various ages with normal or arterial hypertension were investigated. The blood flows of 97 animals were possible to evaluate. It was found that physiological parameters, such as PCO3, pH, PO2 and mean arterial blood pressure within the rather wide limits usually present in the anesthetized animal did not affect the cochlear blood flow to any great extent and that the method is feasible for studies of the blood flow through the inner ear in small animals. PMID- 3108226 TI - Follicle stimulating hormone pattern and luteal function in ewes receiving bovine follicular fluid during three stages of the estrous cycle. AB - The objectives of this study were to determine 1) the ability of charcoal extracted bovine follicular fluid (bFF) to suppress endogenous follicle stimulating hormone (FSH) at various stages of the estrous cycle and 2) the effects of suppression of FSH on luteal function and lengths of the current and subsequent estrous cycles. Twenty-six mature ewes were assigned randomly to receive 5 ml of either bFF or saline, subcutaneously, at 8-h intervals on d 1 through 5 (bFF n = 6; saline n = 3), d 6 through 10 (bFF n = 6; saline n = 3) or d 11 through 15 (bFF n = 6; saline n = 2) of the estrous cycle (d 0 = estrus). Blood was collected daily beginning at estrus and continued until the third estrus (two estrous cycles) or 40 d; more frequent samples were collected 2 h prior to initiation of treatment (0600), hourly for the first 8 h of treatment, then every 4 h until 0800 on the first day after treatment, and finally at 1600 and 2400 on that day. Plasma concentrations of FSH were lower (P less than .001) in bFF-treated than in saline-treated ewes. Treatment with bFF reduced (P less than .05) plasma concentrations of progesterone during the current but not during the subsequent estrous cycle. Treatment with bFF did not affect plasma concentrations of estradiol-17 beta. Administration of bFF on d 11 through 15 of the estrous cycle lengthened the interval from the decline in progesterone to estrus and the inter-estrous interval by approximately 3 and 4 d, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108227 TI - The frequency of in-vitro resistance development to fluoroquinolones and the use of a murine pyelonephritis model to demonstrate selection of resistance in vivo. AB - The frequency of development of resistance to the fluoroquinolones in vitro was generally low with Escherichia coli (in the order of 10(-7) to less than 10(-9) and high with Pseudomonas aeruginosa (in the order of 10(-5) to 10(-7)). Susceptibility to the fluoroquinolones also decreased after serial transfer in increasing concentrations of the drug. Although the MICs for the resistant E. coli variants were higher than that of the parent organism, they were still susceptible to achievable serum concentrations of all the quinolones except nalidixic acid. On the other hand some of the P. aeruginosa variants selected for resistance were resistant to achievable serum concentrations of all the quinolones. When E. coli pyelonephritis in mice was treated with the fluoroquinolones, difloxacin, A-56620, and ciprofloxacin were more effective than norfloxacin and nalidixic acid in lowering viable bacterial counts in the kidneys. The susceptibility of E. coli isolated from kidneys of mice treated with the quinolones was the same as that of the parent strain. When P. aeruginosa pyelonephritis in mice was treated with the fluoroquinolones an initial reduction in the cell count was seen, followed by an increase in the number of resistant variants. The resistant variants differed in their colony morphology and cell envelope proteins. The levels of resistance for the P. aeruginosa variants ranged from a two- to a 64-fold increase in the MIC. PMID- 3108228 TI - Significance of in-vitro penicillin tolerance in experimental enterococcal endocarditis. AB - Although penicillin tolerance has been increasingly recognized among clinical isolates of many Gram-positive organisms, the significance of this phenomenon in vivo is not clear. The present study was performed to characterize penicillin tolerant enterococci by several in-vitro parameters and to examine the significance in vivo in a rabbit model of infective endocarditis. Tolerant enterococci exhibited several characteristics which distinguished them from non tolerant bacteria: significantly greater ratios of MIC to MBC of penicillin, resistance to penicillin-induced lysis and killing, and growth in areas of superinhibitory concentrations of penicillin upon transfer from penicillin gradient to penicillin-free plates. In-vivo studies of aortic valve endocarditis in rabbits treated with procaine penicillin G (300 mg/kg/day) revealed strikingly different responses between infections due to one tolerant and one non-tolerant strain. Animals infected with a tolerant enterococcus showed consistently greater bacterial counts in vegetations during ten days of therapy and significantly lower rates of vegetation sterilization. Serum penicillin levels were not significantly different between the two groups, but serum bactericidal titres were significantly lower for the tolerant than for the non-tolerant strains. These findings indicate that penicillin tolerance identified by several in-vitro criteria is a significant determinant of the in-vivo response of enterococci to penicillin therapy. PMID- 3108230 TI - Saliva lithium monitoring in prepubertal children. PMID- 3108229 TI - Comparative metabolic effects of fructose and glucose in human fibroblast cultures. AB - The comparative metabolic effects of fructose and glucose were determined in human fibroblast cultures. Cells were grown in four different media containing 5.5 and 27.5 mM of glucose and fructose, respectively. For these two hexoses, we compared their uptake, consumption, and conversion into 14CO2 and 14C-lipids. D Fructose was taken up in fibroblasts by an unsaturable process and its consumption was much smaller than that of D-glucose. Whatever the experimental procedure, the glycogen content of cells grown in fructose media was significantly lower than of those grown in glucose media. Labeling of fructose and glucose with 14C showed that more carbon from fructose than from glucose was incorporated into CO2 and glycerolipids. The relative distribution of 14C in the different lipid fractions was similar for both hexoses. These results indicated that the pathways of intermediary metabolism in fibroblast cultures were influenced by the nature of the carbohydrate present in the culture medium and that fructose was a better lipogenic substrate than glucose in human fibroblast cultures. PMID- 3108231 TI - "Giant pigmented hairy nevus in von-Recklinghausen's disease". PMID- 3108232 TI - Sequence analysis of the 17-kilodalton-antigen gene from Rickettsia rickettsii. AB - DNA obtained from the Sheila Smith strain of Rickettsia rickettsii was digested to completion with the restriction endonucleases BamHI and SalI and ligated with the plasmid vector pUC19. The ligation mixture was used to transform Escherichia coli. A total of 465 bacterial clones were screened for antigen production with hyperimmune rabbit serum. One of the reactive clones, containing a recombinant plasmid designated pSS124, was solubilized and subjected to immunoblot analysis and revealed expression of a 17-kilodalton protein reactive with anti-R. rickettsii serum that comigrated with an antigen from R. rickettsii. A 1.6 kilobase PstI-BamHI fragment from pSS124 was subcloned and continued to direct synthesis of the 17-kilodalton antigen. The nucleotide sequence was determined for this 1.6-kilobase subclone, which encompassed the gene encoding the polypeptide as well as flanking regions containing potential regulatory sequences. The open reading frame consisted of 477 nucleotides that specified a 159-amino-acid protein with a calculated molecular weight of 16,840. The deduced amino acid sequence contained a hydrophobic sequence near the amino terminus that resembled signal peptides described for E. coli. The carboxy terminus was hydrophilic in nature and probably contained the exposed epitopes. PMID- 3108233 TI - The phs gene and hydrogen sulfide production by Salmonella typhimurium. AB - Salmonella typhimurium produces H2S from thiosulfate or sulfite. The respective pathways for the two reductions must be distinct as mutants carrying motations in phs, chlA, and menB reduced sulfite, but not thiosulfate, to H2S, and glucose repressed the production of H2S from thiosulfate while it stimulated its production from sulfite. The phs and chlA mutants also lacked a methyl viologen linked thiosulfate reductase activity present in anaerobically grown wild-type cultures. A number of hydroxylamine, transposon Tn10 insertion, and Mu d1(Apr lac) operon fusion mutants defective in phs were characterized. One of the hydroxylamine mutants was an amber mutant, as indicated by suppression of its mutation in a supD background. The temperature-sensitive phs mutants produced H2S and methyl viologen-linked thiosulfate reductase at 30 degrees C but not at 42 degrees C. The reductases in all such mutants grown at 30 degrees C were as thermostable as the wild-type enzyme and did not differ in electrophoretic relative mobility, suggesting that phs is not the structural gene for thiosulfate reductase. Expression of beta-galactosidase in phs::Mu d1(Apr lac) mutants was dependent on anaerobiosis and the presence of reduced sulfur. It was also strongly influenced by carbon source and growth stage. The results are consistent with a model in which the phs gene encodes a regulatory protein essential for the reduction of thiosulfate to hydrogen sulfide. PMID- 3108234 TI - Regulation of expression of pectate lyase genes pelA, pelD, and pelE in Erwinia chrysanthemi. AB - The regulation of pelA, pelD, and pelE genes encoding three of the five major pectate lyase isoenzymes (PLa, PLd, and PLe) in Erwinia chrysanthemi B374 was analyzed by using genetic fusions to lacZ. These three genes are clustered on a 5 kilobase DNA fragment in the order pelD-pelE-pelA and constitute three independent transcriptional units. We localized the pelDEA cluster near the pro-1 marker on the genetic map of B374 by chromosomal mobilization with RP4::mini-Mu plasmid pULB110. Three classes of regulatory mutations responsible for constitutive pectate lyase synthesis have been described (kdgR, gpiR, and cri). We studied the effects of each mutation on pelE, pelD, and pelA expression independently. The mutations kdgR and gpiR mainly affect the expression of pelE and pelD, although PLa synthesis is slightly increased. The cri mutation results in a low level of constitutive expression of the three pel genes, but it is a pleiotropic mutation since other genes not involved in pectinolysis are also affected. In addition, we demonstrated that exuR, a negative regulatory gene governing the catabolism of hexuronates, does not modify the expression of pel genes. The frequency of gpiR or cri mutations (about 10(-8)) and the resulting constitutivity of pectate lyase synthesis suggest that these genes act as negative regulatory genes in addition to kdgR, which is already known to encode a repressor. Moreover, we found that expression of pel-lac fusions carried on pBR322 derivatives was higher in E. chrysanthemi than in Escherichia coli; this fact suggests the existence of positive regulation of pectate lyase synthesis in E. chrysanthemi. PMID- 3108236 TI - Alteration of the Fe protein of nitrogenase by oxygen in the cyanobacterium Anabaena sp. strain CA. AB - Changes in protein composition were noted when heterocysts of Anabaena sp. strain CA were isolated from filaments grown in 1% CO2-99% N2 and subsequently exposed to oxygen. Immunospecific Western blot analysis showed that the Fe protein of nitrogenase is altered. In cells grown under microaerobic conditions, the Fe protein was found in a form with an apparent molecular weight of 30,000. Exposure to oxygen caused a shift in the migration of this polypeptide to a position corresponding to an apparent molecular weight of 31,500. This modification was reversible upon removal of oxygen from the culture. Chloramphenicol did not inhibit the alteration in either direction. Suppression by ammonium nitrate of the recovery of nitrogenase activity from the effects of oxygen did not prevent the alteration of the protein. Other inhibitors of nitrogenase activity, (metronidazole, carbonyl cyanide m-chlorophenylhydrazone, and phenazine methosulfate) were tested for their effect on Fe protein modification. Alteration of the Fe protein may relate to the protection of nitrogenase from the deleterious effects of oxygen. PMID- 3108235 TI - Creation of a test plasmid for detecting G-C-to-T-A transversions by changing serine to arginine in the active site of beta-lactamase. AB - Oligonucleotide-directed mutagenesis of the beta-lactamase gene, bla, on pBR322 was used to change the codon for the active-site serine 70, AGC, to CGC, coding for arginine. Escherichia coli cells carrying the mutant plasmid, pGD104, were sensitive to ampicillin, indicating that the arginine-containing enzyme is inactive. We characterized the reversion of the mutant bla gene by a number of mutagens and in different genetic backgrounds and demonstrated that full ampicillin resistance can be restored only by a G-C-to-T-A transversion occurring at the first base of the codon. Thus, reversion of the mutant bla gene is diagnostic for G-C-to-T-A transversions, and bacteria carrying pGD104 can be used as test strains to detect the occurrence of this mutation. PMID- 3108237 TI - Genetic characterization of a highly efficient alternate pathway of serine biosynthesis in Escherichia coli. AB - There exists in Escherichia coli a known set of enzymes that were shown to function in an efficient and concerted way to convert threonine to serine. The sequence of reactions catalyzed by these enzymes is designated the Tut cycle (threonine utilization). To demonstrate that the relevant genes and their protein products play essential roles in serine biosynthesis, a number of mutants were analyzed. Strains of E. coli with lesions in serA, serB, serC, or glyA grew readily on minimal medium supplemented with elevated levels of leucine, arginine, lysine, threonine, and methionine. No growth on this medium was observed upon testing double mutants with lesions in one of the known ser genes plus a second lesion in glyA (serine hydroxymethyltransferase), gcv (the glycine cleavage system), or tdh (threonine dehydrogenase). Pseudorevertants of ser mutants capable of growth on either unsupplemented minimal medium or medium supplemented with low levels of leucine, arginine, lysine, threonine, and methionine were isolated. At least two unlinked mutations were associated with such phenotypes. PMID- 3108238 TI - Isolation and characterization of light-regulated phycobilisome linker polypeptide genes and their transcription as a polycistronic mRNA. AB - Several cyanobacteria adjust both the phycobiliprotein and linker protein composition of the phycobilisome, a light-harvesting complex in cyanobacteria and some eucaryotic algae, to maximize absorption of prevalent wavelengths of light. This process is called complementary chromatic adaptation. We sequenced the amino terminus of a linker polypeptide which is associated with phycocyanin and accumulates to high levels during growth of the cyanobacterium Fremyella diplosiphon in red light. A mixed oligonucleotide encoding a region of this amino terminus was synthesized and used to identify a fragment of F. diplosiphon genomic DNA encoding the linker polypeptide. This linker gene was located between two other linker genes and contiguous to the red-light-induced phycocyanin gene set. Sequences of all three linker genes are presented. These genes were transcribed together onto a large polycistronic mRNA which also encoded the red light-induced phycocyanin subunits. The relationship of this transcript to the biogenesis of the phycobilisome when F. diplosiphon is grown under different conditions of illumination is discussed. PMID- 3108240 TI - Neutral amino acid transport by membrane vesicles of Streptococcus cremoris is subject to regulation by internal pH. AB - The pH dependence of transport of the neutral amino acids L-serine and L-alanine by membrane vesicles of Streptococcus cremoris have been studied in detail. The rates of four modes of facilitated diffusion (e.g., influx, efflux, exchange, and counterflow) of L-serine and L-alanine increase with increasing H+ concentration. Rates of artificially imposed electrical potential across the membrane (delta psi)-driven transport of L-serine and L-alanine show an optimum at pH 6 to 6.5. Under similar conditions, delta psi- and pH gradient across the membrane (delta pH)-driven transport of L-leucine is observed within the pH range studied (pH 5.5 to 7.5). The effect of ionophores on the uptake of L-alanine and L-serine has been studied in membrane vesicles of S. cremoris fused with proteoliposomes containing beef heart mitochondrial cytochrome c oxidase as a proton motive force (delta p)-generating system (Driessen et al., Proc. Natl. Acad. Sci. USA 82:7555 7559, 1985). An increase in the initial rates of L-serine and L-alanine uptake is observed with decreasing pH, which is not consistent with the pH dependency of delta p. Nigericin, an ionophore that induced a nearly complete interconversion of delta pH into delta psi, stimulated both the rate and the final level of L alanine and L-serine uptake. Valinomycin, an ionophore that induced a collapse of delta psi with a noncompensating increase in delta pH, inhibited L-alanine and L serine uptake above pH 6.0 more efficiently than it decreased delta p. Experiments which discriminate between the effects of the internal pH and the driving force (delta pH) on solute transport indicate that at high internal pH the transport systems for L-alanine and L-serine are inactivated. A unique relation exists between the internal pH and the initial rate of uptake of L serine and L-alanine with an apparent pK of 7.0. The rate of L-alanine and L serine uptake decreases with increasing internal pH. The apparent complex relation between the delta p and transport of L-alanine and L-serine can be explained by a regulatory effect of the internal pH on the activity of the L serine and L-alanine carriers. PMID- 3108239 TI - Molecular cloning and characterization of the recA gene from the cyanobacterium Synechococcus sp. strain PCC 7002. AB - The recA gene of Synechococcus sp. strain PCC 7002 was detected and cloned from a lambda gtwes genomic library by heterologous hybridization by using a gene internal fragment of the Escherichia coli recA gene as the probe. The gene encodes a 38-kilodalton polypeptide which is antigenically related to the RecA protein of E. coli. The nucleotide sequence of a portion of the gene was determined. The translation of this region was 55% homologous to the E. coli protein; allowances for conservative amino acid replacements yield a homology value of about 74%. The cyanobacterial recA gene product was proficient in restoring homologous recombination and partial resistance to UV irradiation to recA mutants of E. coli. Heterologous hybridization experiments, in which the Synechococcus sp. strain PCC 7002 recA gene was used as the probe, indicate that a homologous gene is probably present in all cyanobacterial strains. PMID- 3108241 TI - Novel alkaline- and heat-stable serine proteases from alkalophilic Bacillus sp. strain GX6638. AB - An alkalophilic Bacillus sp., strain GX6638 (ATCC 53278), was isolated from soil and shown to produce a minimum of three alkaline proteases. The proteases were purified by ion-exchange chromatography and were distinguishable by their isoelectric point, molecular weight, and electrophoretic mobility. Two of the proteases, AS and HS, which exhibited the greatest alkaline and thermal stability, were characterized further. Protease HS had an apparent molecular weight of 36,000 and an isoelectric point of approximately 4.2, whereas protease AS had a molecular weight of 27,500 and an isoelectric point of 5.2. Both enzymes had optimal proteolytic activities over a broad pH range (pH 8 to 12) and exhibited temperature optima of 65 degrees C. Proteases HS and AS were further distinguished by their proteolytic activities, esterolytic activities, sensitivity to inhibitors, and their alkaline and thermal stability properties. Protease AS was extremely alkali stable, retaining 88% of initial activity at pH 12 over a 24-h incubation period at 25 degrees C; protease HS exhibited similar alkaline stability properties to pH 11. In addition, protease HS had exceptional thermal stability properties. At pH 9.5 (0.1 M CAPS buffer, 5 mM EDTA), the enzyme had a half-life of more than 200 min at 50 degrees C and 25 min at 60 degrees C. At pH above 9.5, protease HS readily lost enzymatic activity even in the presence of exogenously supplied Ca2+. In contrast, protease AS was more stable at pH above 9.5, and Ca2+ addition extended the half-life of the enzyme 10 fold at 60 degrees C. In contrast, protease AS was more stable at pH above 9.5, and Ca2+ addition extended the half-life of the enzyme 10-fold at 60 degrees C. The data presented here clearly indicate that these two alkaline proteases from Bacillus sp. strain GX6638 represent novel proteases that differ fundamentally from the proteases previously described for members of the genus Bacillus. PMID- 3108243 TI - Conformation of the constant fragment of the immunoglobulin light chain: effect of cleavage of the polypeptide chain and the disulfide bond. AB - In order to understand the conformations and stabilities of the immunoglobulin domains, a derivative of the type-lambda constant fragment in which the peptide bond Arg190-Ser191 is cleaved and a derivative of the type-kappa constant fragment in which the peptide bond Arg142-Glu143 is cleaved were prepared by limited proteolysis with the proteinase from mouse submaxillary gland, endoproteinase Arg-C [EC 3.4.21.40]. The cleaved peptide bond of each derivative is located in the loop formed by the intrachain disulfide bond and the two peptides formed are linked by the disulfide bond. The two nicked CL fragments did not assume any ordered conformation. On the other hand, a derivative in which the intrachain disulfide bond is reduced had a conformation very similar to that of the intact CL fragment, although the stability was considerably low. Since the entropy of the nicked fragment should be nearly the same as that of the reduced CL fragment in the unfolded state, a destabilizing effect of cleavage of the polypeptide bond in the folded state in addition to the entropic effect in the unfolded state seems necessary to account for the conformations of the nicked CL fragments. PMID- 3108242 TI - Genetic structure of Neisseria meningitidis populations in relation to serogroup, serotype, and outer membrane protein pattern. AB - The genetic structure of populations of Neisseria meningitidis was examined by an analysis of electrophoretically demonstrable allelic variation at 15 genes encoding enzymes in 650 isolates of eight serogroups (A, B, C, W135, X, Y, Z, and 29E) and 38 nonserogroupable isolates. A total of 331 distinctive multilocus genotypes (electrophoretic types, ETs) was identified, among which mean genetic diversity per locus (H = 0.547) was greater than in Escherichia coli and other bacterial species thus far studied. The intercontinental distribution of some ETs and the recovery of organisms of identical genotype over periods of many years strongly suggest that the genetic structure of N. meningitidis is basically clonal as a consequence of low rates of recombination of chromosomal genes. Variation among strains in serogroup, serotype, and the electrophoretic pattern of the major outer membrane proteins has little relationship to the complex structure of populations revealed by enzyme electrophoresis, which involves 14 major lineages of clones diverging from one another at genetic distances greater than 0.50. Genetic diversity among ETs of isolates of the same serogroup was, on average, 84% of that in the total sample. Clones of serogroup A were unusual in being genotypically less heterogeneous than those of other serogroups and in forming a single phylogenetic group. Isolates of the same serotype or outer membrane protein pattern were also highly heterogeneous; on average, 87 and 97%, respectively, of the total species diversity was represented by ETs of the same serotype or outer membrane protein. PMID- 3108244 TI - Phosphorylation of RNA polymerase I-associated polypeptides of Tetrahymena pyriformis. AB - In the ciliate Tetrahymena pyriformis phosphorylation of RNA polymerase I [EC 2.7.7.6] and of polymerase-associated polypeptides was investigated in growing and growth-arrested cultures which differ widely in their rates of rRNA synthesis. Several putative subunits of RNA polymerase I (of 180, 21.5, and 19.5 kDa) and a polymerase-associated polypeptide of 27 kDa were found to be phosphorylated, independent of the growth conditions. However, an additional enzyme-associated polypeptide of 26 kDa was intensively labeled with 32P only after arrestment of growth by starvation. The molar quantities of both phosphorylated, enzyme-associated polypeptides thereby did not differ in growing and growth-arrested cultures, and the specific 32P-labeling of cellular ATP remained nearly unchanged under the different culture conditions. These findings indicate a selective, reversible phosphorylation of the RNA polymerase I associated 26 kDa polypeptide correlated with conditions of repressed rRNA synthesis induced by the starvation procedure. In vitro phosphorylation in macronuclei isolated from growing and growth-arrested cultures using [gamma 32P]ATP revealed essentially the same pattern of labeling of the enzyme associated polypeptides of 27 and 26 kDa as it was found in vivo. PMID- 3108245 TI - Euglena gracilis cadmium-binding protein-II contains sulfide ion. AB - Sulfide ions are a constituent of the cadmium-binding protein-II in the alga Euglena gracilis. Their presence was demonstrated by the methylene blue assay, by acid labilization induced reductions in the Cd-S charge transfer band at 254 nm and by reactions with the thiol reagent, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). Direct reduction of DTNB by sulfide and precipitation of CdS yield a complex stoichiometry for the DTNB reaction. The S2-/Cd2+ ratios determined, 1.25 +/- 0.10 (methylene blue) and 1.37 +/- 0.16 (DTNB), are in good agreement. PMID- 3108246 TI - In vivo regulation of hepatic LDL receptor mRNA in the baboon. Differential effects of saturated and unsaturated fat. AB - The effects of diets enriched with cholesterol and different fats upon plasma lipoproteins and hepatic low density lipoprotein (LDL) receptor mRNA levels were studied in a group of 18 normal baboons. Animals were fed diets containing 1% cholesterol and 25% fat as either coconut oil, peanut oil, or olive oil for a period of 20 weeks. Plasma total cholesterol, high density lipoprotein (HDL) cholesterol, beta-lipoprotein (LDL + very low density lipoprotein) cholesterol, apolipoprotein B and apolipoprotein A-I were measured in samples obtained at 4 week intervals. All three diet groups demonstrated a statistically significant increase in plasma cholesterol as compared to base line throughout the experiment. Hepatic LDL receptor (LDL-R) mRNA levels were quantified by dot blot hybridization in serial liver biopsies. Animals fed saturated fat sustained a significant reduction in hepatic LDL-R mRNA as compared to those fed either monounsaturated or polyunsaturated fat. A strong negative correlation between LDL R mRNA and plasma total cholesterol (r = -0.71), HDL cholesterol (r = -0.76), and plasma apo A-I (r = -0.77) was observed only in those animals fed coconut oil. Weak negative correlations between LDL-R mRNA and other plasma parameters did not achieve statistical significance. We conclude that saturated and unsaturated oils may influence plasma cholesterol levels in part through differential effects on LDL receptor biosynthesis in baboons. PMID- 3108247 TI - Lethal perinatal osteogenesis imperfecta due to the substitution of arginine for glycine at residue 391 of the alpha 1(I) chain of type I collagen. AB - A baby with the lethal perinatal form of osteogenesis imperfecta was shown to have a structural defect in the alpha 1(I) chain of type I procollagen. Normal and mutant alpha 1(I) CB8 cyanogen bromide peptides, from the helical part of the alpha 1(I) chains, were purified from bone. Amino acid sequencing of tryptic peptides derived from the mutant alpha 1(I) CB8 peptide showed that the glycine residue at position 391 of the alpha 1(I) chain had been replaced by an arginine residue. This substitution accounted for the more basic charged form of this peptide that was observed on two-dimensional electrophoresis of the collagen peptides obtained from the tissues. The substitution was associated with increased enzymatic hydroxylation of lysine residues in the alpha 1(I) CB8 and the adjoining CB3 peptides but not in the carboxyl-terminal CB6 and CB7 peptides. This finding suggested that the sequence abnormality had interfered with the propagation of the triple helix across the mutant region. The abnormal collagen was not incorporated into the more insoluble fraction of bone collagen. The baby appeared to be heterozygous for the sequence abnormality and as the parents did not show any evidence of the defect it is likely that the baby had a new mutation of one allele of the pro-alpha 1(I) gene. The amino acid substitution could result from a single nucleotide mutation in the codon GGC (glycine) to produce the codon CGC (arginine). PMID- 3108248 TI - Structure, evolution, and regulation of chicken apolipoprotein A-I. AB - A full-length cDNA clone for the precursor form of chicken liver apolipoprotein A I (apoA-I) was isolated by antibody screening of a chicken liver cDNA library in the expression vector lambda gt11. The complete nucleotide sequence and predicted amino acid sequence of this clone is presented. The identity of the clone was confirmed by comparison with partial amino acid sequences for chicken apolipoprotein A-I. Chicken preproapolipoprotein A-1 consists of an 18-amino acid prepeptide, a 6-amino acid propeptide, and 240 amino acids of mature protein. The sequence of the protein is homologous to mammalian apoA-I and is highly internally repetitive, consisting largely of 11-amino acid repeats predicted to have an amphipathic alpha-helical structure. The sequence of the propeptide (Arg Ser-Phe-Trp-Gln-His) differs in two positions from that of mammalian apoA-I. The mRNA for chicken apoA-I is about 1 kilobase in length and is expressed in a variety of tissues including liver, intestine, brain, adrenals, kidneys, heart, and muscle. This quantitative tissue distribution has been determined and is similar to that observed for mammalian apoE and different from that of mammalian apoA-I mRNA. This reinforces the concept that avian apoA-I performs functions analogous to those of mammalian apoE. Moreover, comparisons revealed sequences of chicken apoA-I similar to the region of mammalian apoE responsible for interaction with cellular receptors. Previous studies have demonstrated striking changes in the rates of synthesis of apoA-I in breast muscle during development and in optic nerve after retinal ablation. We now demonstrate that these changes are paralleled by changes in mRNA levels. ApoA-I mRNA levels increase approximately 50-fold in breast muscle between 14 days postconception and hatching and then decrease about 15-fold to adult levels. The levels of apoA-I mRNA increase about 3-fold in optic nerve following retinal ablation. ApoA-I mRNA is also found in the brain in the absence of nerve injury. This may indicate that locally synthesized apoA-I has a routine or housekeeping function in lipid metabolism in the central nervous system. PMID- 3108249 TI - Variability of the intracellular ionic environment of Escherichia coli. Differences between in vitro and in vivo effects of ion concentrations on protein DNA interactions and gene expression. AB - Effects of changes in intracellular ion concentrations on the interactions of Escherichia coli lac repressor with lac operator mutants and on the interactions of RNA polymerase with various promoters have been investigated in vivo. The intracellular ionic environment was reproducibly varied by changing the osmolality of the 4-morpholinepropanesulfonic acid minimal growth medium. As the osmolality of the growth medium is varied from 0.1 to 1.1 osmolal, the total intracellular concentration of K+ increases linearly from 0.23 +/- 0.03 to 0.93 +/- 0.05 molal and the total intracellular concentration of glutamate increases linearly from 0.03 +/- 0.01 to 0.26 +/- 0.02 molal. The sum of the changes in the total concentrations of these two ions appears sufficient to compensate for a given change in external osmolality, indicating that K+ and glutamate are the primary ionic osmolytes under these conditions and that these ions are free in the cytoplasm. In support of this, in vivo 39K NMR experiments as a function of external osmolality indicate that changes in the total cytoplasmic K+ concentration correspond to changes in the free cytoplasmic K+ concentration. Extents of interaction of lac repressor and RNA polymerase with their specific DNA sites were monitored by measuring the amounts of beta-galactosidase produced under the control of these sites. For both lac repressor and RNA polymerase, it was found that formation of functional protein-DNA complexes in vivo is only weakly (if at all) dependent on intracellular ion concentration. These results contrast strongly with those obtained on these systems in vitro, which showed that both the equilibria and kinetics of binding are extremely salt-dependent. We discuss several possible mechanisms by which E. coli may compensate for the potentially disruptive effects of these large changes in the intracellular ionic environment. PMID- 3108250 TI - Regulation of N-carbamoyl-beta-alanine amidohydrolase, the terminal enzyme in pyrimidine catabolism, by ligand-induced change in polymerization. AB - N-Carbamoyl-beta-alanine (NC beta A) amidohydrolase (EC 3.5.1.6) is regulated in opposing fashion by the substrate, NC beta A and the product, beta-alanine. The native enzyme from rat liver has a molecular weight of 235,000 in the absence of ligands. NC beta A and substrate analogs (N-amidino-beta-alanine, N-carbamoyl glycine) produced association of the enzyme. beta-Alanine and its analog gamma aminobutyrate caused dissociation of the enzyme and produced inhibition. Negative cooperativity was observed for the binding of all ligands as measured by the change in polymerization of the enzyme, with an average Hill coefficient (napp) of 0.5. Enzyme that had been dissociated by preincubation with beta-alanine had little or no initial activity; only after a lag of 9 s was a steady state progress curve evident. The existence of a regulatory site is proposed as a model to explain physical and kinetic data. The enzyme activity was highest in rat liver and detectable in kidney; activity was not detected in brain, lung, muscle, or spleen of rat, nor in mouse Ehrlich ascites tumor cells. The rat liver enzyme has a pH optimum of 6.8, with a Km of 6.5 microM for NC beta A and a Ki of 1.08 mM for beta-alanine at this pH. PMID- 3108251 TI - Purification and characterization of Ca2+/calmodulin-dependent protein kinase I from bovine brain. AB - Ca2+/calmodulin-dependent protein kinase (Ca2+/CaM kinase I), which phosphorylates site I of synapsin I, has been highly purified from bovine brain. The physical properties and substrate specificity of Ca2+/CaM kinase I were distinct from those of all other known Ca2+/CaM kinases. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that the purified enzyme preparation consisted of two major polypeptides of Mr 37,000 and 39,000 and a minor polypeptide of Mr 42,000. In the presence of Ca2+ and calmodulin (CaM), all three polypeptides bound CaM, were autophosphorylated on threonine residues, and were labeled by the photoaffinity label 8-azido-ATP. Peptide maps of the three autophosphorylated polypeptides were very similar. The Stokes radius and the sedimentation coefficient of the enzyme were, respectively, 31.8 A and 3.25 s. A molecular weight of 42,400 and a frictional ratio of 1.38 were calculated from the above values, suggesting that Ca2+/CaM kinase I is a monomer. It is possible that the polypeptides of lower molecular weight are derived from the polypeptide of Mr 42,000 by proteolysis; alternatively, the polypeptides may represent isozymes of Ca2+/CaM kinase I. Synapsin I (site I) was the best substrate tested (Km, 2-4 microM) for Ca2+/CaM kinase I. Of many additional proteins tested, only protein III (a phosphoprotein related to synapsin I) and smooth muscle myosin light chain were phosphorylated. Ca2+/CaM kinase I was found in highest concentration in brain, where it showed widespread regional and subcellular distributions. In addition, the enzyme had a widespread and predominantly cytosolic tissue distribution. The widespread neuronal and tissue distribution of Ca2+/CaM kinase I suggests that other substrates might exist for this enzyme in both neuronal and non-neuronal tissues. PMID- 3108252 TI - Fast atom bombardment mass spectrometry and tandem mass spectrometry of biologically active peptidoglycan monomers from Neisseria gonorrhoeae. AB - Fast atom bombardment mass spectrometry (FABMS) and tandem mass spectrometry (MS/MS) were employed to define the structures of Neisseria gonorrhoeae peptidoglycan monomers that were of interest because of their abilities to mediate diverse biological reactions ranging from arthritogenicity to somogenicity. FABMS-determined molecular weights of individual components present in several different enzymatically derived classes of gonococcal monomers revealed that each of these classes was a complex mixture of up to 13 distinct peptidoglycan fragments. These ranged from the predominant disaccharide tetrapeptides possessing reducing or nonreducing 1,6-anhydro-N-acetylmuramic acid ends to relatively minor constituents containing glycine or asparagine in addition to traditional peptidoglycan amino acids, i.e. alanine, glutamic acid, and diaminopimelic acid. FABMS of high performance liquid chromatography-purified monomers yielded some sequence information; however, analysis even of unfractionated peptidoglycan mixtures using a JEOL HX110/HX110 tandem mass spectrometer operating at 10 kV provided unambiguous primary sequence data for the peptidoglycan monomers and defined the position of glycine in four compounds as well as the location of O-acetyl substituents (present on some compounds) on C 6 of the N-acetylmuramic acid residue. PMID- 3108253 TI - The role of asparagine-linked carbohydrate in natural killer cell-mediated cytolysis. AB - Chinese hamster ovary cell lines with specific lesions in the formation of glycoconjugates were tested for their sensitivity to lysis by interferon-boosted human natural killer cells. We report here that the type of asparagine-linked carbohydrate present on target cell glycoproteins determines their susceptibility to natural killer lysis. The targets tested were Chinese hamster ovary parent cells and Lec1, Lec2, and Lec8 mutants. Lec8 and Lec2 cells show an overall reduction of galactose and/or sialic acid in their glycoconjugates due to defects in the translocation of UDP-galactose and CMP-sialic acid, respectively. Due to a specific block in N-linked carbohydrate processing, Lec1 cells produce only high mannose-type oligosaccharides, but their glycolipids are identical to those of the parent. Both Lec2 and Lec8 mutants are more sensitive to natural killer lysis than the parent cells. This is consistent with their extensive reduction in cell surface sialic acid. Furthermore, Lec1 mutants are more susceptible to natural killer lysis than the parent cells. To confirm that the increased natural killer sensitivity of Lec1 cells was due to the modification of N-linked carbohydrate, parent cells were treated with swainsonine, a specific inhibitor of N-linked oligosaccharide processing. Swainsonine-treated parent cells are nearly as sensitive to natural killer lysis as the Lec1 mutants. PMID- 3108255 TI - Eggs of the sea urchin, Strongylocentrotus purpuratus, contain a prominent (11R) and (12R) lipoxygenase activity. AB - Recent work has shown that oocytes of the starfish synthesize (8R) hydroxyeicosatetraenoic acid and that this eicosanoid has a potent and highly specific action in induction of oocyte maturation. These striking results prompted us to examine the lipoxygenase activity of eggs of the sea urchin Strongylocentrotus purpuratus. Four hydroxyeicosanoids were formed in homogenates of sea urchin eggs; their structures and stereochemistry were characterized by high pressure liquid chromatography, UV spectroscopy, and gas chromatography-mass spectrometry. The compounds were identified as (11R)-hydroxy-5,8,12,14-ZZEZ eicosatetraenoic acid and (12R)-hydroxy-5,8,10,14-ZZEZ-eicosatetraenoic acid (from arachidonic acid) and the corresponding (11R)- and (12R)-hydroxy analogs of eicosapentaenoic acid. The formation of these egg products was not blocked by a cyclooxygenase inhibitor, indomethacin (10 microM), and their precise structures are consistent with their formation by a lipoxygenase reaction. Eicosapentaenoic acids with a prochiral tritium label in the 10-D or 10-L position were used to investigate the mechanism of biosynthesis. The formation of (12R) hydroxyeicosapentaenoic acid proceeded with the stereoselective abstraction of the 10-D hydrogen from the substrate. This reaction was shown to be opposite to the (12S) oxygenation catalyzed by porcine leukocyte 12-lipoxygenase. These results with S. purpuratus eggs constitute the first demonstration of (11R)- or (12R)-lipoxygenase activity in any cell type or tissue. PMID- 3108254 TI - The factor IX phospholipid-binding site is required for calcium-dependent activation of factor IX by factor XIa. AB - To determine the functional role of the metal-dependent conformational changes in Factor IX, two populations of conformation-specific anti-Factor IX antibodies were prepared. Anti-Factor IX X Mg(II) antibodies bind to Factor IX in the presence of Mg(II) and other metal ions, but not in the absence of metal ions. Anti-Factor IX X Ca(II)-specific antibodies bind to Factor IX in the presence of Ca(II) and Sr(II), but not in the presence of Mn(II), Mg(II), and Ba(II). In the presence of a metal ion that induces the conformational transition recognized by the anti-Factor IX X Mg(II) antibodies, the concentrations of CaCl2 and SrCl2 needed for the half-maximal binding of the anti-Factor IX X Ca(II)-specific antibodies to Factor IX were reduced 3- and 20-fold, respectively. Factor IX binding to phospholipid vesicles was inhibited by the Fab fragments of the anti Factor IX X Ca(II)-specific antibodies, but was not inhibited by the Fab fragments of the anti-Factor IX X Mg(II) antibodies. Factor XIa activation of Factor IX was also inhibited by the Fab fragments of the anti-Factor IX X Ca(II) specific antibodies, but not by the anti-Factor IX X Mg(II) antibodies. These results support the hypothesis that Factor IX undergoes two metal-dependent conformational transitions: FIX----FIX'----FIX*. The first transition (FIX--- FIX') is metal-dependent but cation-nonselective; the second transition (FIX'--- FIX*) is metal-selective for Ca(II) or Sr(II). The second transition results in the expression of conformational determinants necessary for membrane binding and the Ca(II)-dependent activation of Factor IX by Factor XIa. These results suggest chemical similarity between a surface of a domain of Factor XIa and phospholipid vesicles, both of which interact with Factor IX in the presence of Ca(II). PMID- 3108256 TI - Mechanisms subserving the steroidogenic synergism between follicle-stimulating hormone and insulin-like growth factor I (somatomedin C). Alterations in cellular sterol metabolism in swine granulosa cells. AB - Swine granulosa cells respond to follicle-stimulating hormone (FSH) and the insulin-like growth factor, IGF-I (somatomedin C), with synergistic increases in progesterone production. This facilitative interaction was not attributable to decreased catabolism of progesterone to 20 alpha-hydroxypregn-4-en-3-one, but rather to enhanced pregnenolone biosynthesis observed in response to provision of 25-hydroxycholesterol as exogenous sterol substrate. The latter evidence of increased functional cholesterol side-chain cleavage activity was accompanied by augmented incorporation of [35S]methionine into specific immunoisolated components of the cholesterol side-chain cleavage apparatus, viz. cytochrome P 450scc and adrenodoxin. The synergism between FSH and IGF-I could be sustained over 4 days of serum-free monolayer culture. Under these conditions, compactin, a competitive inhibitor of de novo endogenous cholesterol biosynthesis, suppressed stimulated progesterone production by approximately equal to 50%. However, synergism was not expressed at the levels of [14C]acetate incorporation into nonsaponifiable lipids or endogenous 3-hydroxy-3-methylglutaryl coenzyme A reductase activity per se. Conversely, exogenous sterol substrate provided in the form of low-density lipoprotein (LDL)-borne cholesterol increased the absolute magnitude of the combined actions of IGF-I and FSH by 3-6-fold. This increase in steroidogenesis in response to LDL was associated with enhanced surface binding, internalization, and degradation of [125I] iodo-LDL. In addition, when granulosa cells were incubated with [3H]cholesteryl linoleate-labeled LDL, FSH and IGF-I synergistically augmented the intracellular accumulation of [3H]cholesterol and [3H]cholesteryl ester and the production of [3H]progesterone. Moreover, FSH and IGF-I coordinately increased the total mass of free and esterified cholesterol contained in granulosa cells. We conclude that FSH and IGF-I can augment absolute rates of progestin biosynthesis by granulosa cells by activating dual mechanisms: stimulation of functional cholesterol side chain cleavage activity and enhancement of effective cellular uptake and utilization of low-density lipoprotein-borne sterol substrate. PMID- 3108257 TI - Malic enzyme from archaebacterium Sulfolobus solfataricus. Purification, structure, and kinetic properties. AB - An NADP-preferring malic enzyme ((S)-malate:NADP oxidoreductase (oxalacetate decarboxylating) EC 1.1.1.40) with a specific activity of 36.6 units per mg of protein at 60 degrees C and an isoelectric point of 5.1 was purified to homogeneity from the thermoacidophilic archaebacterium Sulfolobus solfataricus, strain MT-4. The purification procedure employed ion exchange chromatography, ammonium sulfate fractionation, affinity chromatography, and gel filtration. Molecular weight determinations demonstrated that the enzyme was a dimer of Mr 105,000 +/- 2,000 with apparently identical Mr 49,000 +/- 1,500 subunits. Amino acid composition of S. solfataricus enzyme was determined and found to be significantly higher in tryptophan content than the malic enzyme from Escherichia coli. In addition to the NAD(P)-dependent oxidative decarboxylation of L-malate, S. solfataricus malic enzyme was able to catalyze the decarboxylation of oxalacetate. The enzyme absolutely required divalent metal cations and it displayed maximal activity at 85 degrees C and pH 8.0 with a turnover number of 376 s-1. The enzyme showed classical saturation kinetics and no sigmoidicity was detected at different pH values and temperatures. At 60 degrees C and in the presence of 0.1 mM MnCl2, the Michaelis constants for malate, NADP, and NAD were 18, 3, and 250 microM, respectively. The S. solfataricus malic enzyme was shown to be very thermostable. PMID- 3108258 TI - Properties of talin from chicken gizzard smooth muscle. AB - This paper describes the structural and biochemical characterization of talin, a protein localized to various cellular sites where bundles of actin filaments attach to the plasma membrane. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the protein has a molecular mass of 225,000 +/- 5,000 daltons. Hydrodynamic measurements at protein concentrations less than 0.72 mg/ml indicate a monomeric protein with a native molecular mass of 213,000 +/- 15,000 daltons. Sedimentation equilibrium experiments indicate self-association at protein concentrations of 0.72 mg/ml and higher. The data suggest that this self association is a simple monomer:dimer equilibrium over the range of concentrations observed. At low protein concentrations where talin is a monomer, the Stokes radius and sedimentation coefficient vary with ionic strength. Under low ionic strength conditions (5-20 mM NaCl), talin has a Stokes radius of 6.5 nm and a sedimentation value of 9.4, suggesting an asymmetric globular molecule; whereas under high ionic strength conditions (200 mM NaCl), the Stokes radius increases to 7.7 nm and the sedimentation coefficient decreases to 8.8, suggesting a more elongated protein. This conformation change is confirmed by electron microscopy which reveals a more globular protein at low ionic strength which unfolds to become an elongated flexible molecule as the ionic strength is increased to physiological and higher levels. The amino acid composition of talin indicates a low level of aromatic residues, consistent with its relatively low extinction coefficient, talin has an isoelectric point between pH 6.7 and 6.8 based on isoelectric focusing. The detailed purification of talin is described. PMID- 3108259 TI - Selective inhibition of catalytic activity of smooth muscle myosin light chain kinase. AB - Systematically synthesized derivatives of ML-9, 1-(5-chloronaphthalenesulfonyl) 1H-hexahydro-1,4-diazepine, were found to inhibit both Ca2+-calmodulin-dependent and -independent smooth muscle myosin light chain kinases with a similar concentration dependence, and their inhibitions were of the competitive type with respect to ATP. Moreover, ML-9 as well as ATP or ADP exhibited an effective protection to inactivation of smooth muscle myosin light chain kinase by the nucleotide affinity label 5'-p-fluorosulfonylbenzoyladenosine, suggesting that ML 9 binds at or near the ATP-binding site on the kinase molecule. These derivatives, which were structurally unrelated to ATP and exhibited more hydrophobic properties detected by reverse-phase high-performance liquid chromatography, exhibited more potent inhibition toward smooth muscle myosin light chain kinase, indicating that the hydrophobic properties of these derivatives positively correlated well with their potencies of inhibiting the catalytic activity for the enzyme. These findings suggest that the ATP-binding site at the active center of smooth muscle myosin light chain kinase is located in a hydrophobic environment. The potent vaso-relaxing effect of ML-9 on rabbit vascular strips and on saponin-treated skinned smooth muscle cells was discussed in relation to the in vivo inhibition by this drug of smooth muscle myosin light chain kinase. PMID- 3108260 TI - Requirement of pro-sequence for the production of active subtilisin E in Escherichia coli. AB - Subtilisin E, an alkaline serine protease of Bacillus subtilis 168, is first produced as a precursor, pre-pro-subtilisin, which consists of a signal peptide for protein secretion (pre-sequence) and a peptide extension of 77 amino acid residues (pro-sequence) between the signal peptide and mature subtilisin. When the entire coding region for pre-pro-subtilisin E was cloned into an Escherichia coli expression vector, active mature subtilisin E was secreted into the periplasmic space. When the pre-sequence was replaced with the E. coli OmpA signal peptide, active subtilisin E was also produced. When the OmpA signal peptide was directly fused to the mature subtilisin sequence, no protease activity was detected, although this product had the identical primary structure as subtilisin E as a result of cleavage of the OmpA signal peptide and was produced at a level of approximately 10% of total cellular protein. When the OmpA signal peptide was fused to the 15th or 44th amino acid residue from the amino terminus of the pro-sequence, active subtilisin was also not produced. These results indicate that the pro-sequence of pre-pro-subtilisin plays an important role in the formation of enzymatically active subtilisin. It is proposed that the pro-sequence is essential for guiding appropriate folding of the enzymatically active conformation of subtilisin E. PMID- 3108261 TI - The late results of tarsometatarsal joint injuries. AB - The late results of tarsometatarsal injuries in 33 patients have been reviewed. The average follow-up period was 15 years (range 11 to 20 years). Methods of treatment included cast immobilisation, and closed or open reduction with or without internal fixation. All patients noted diminishing symptoms after injury and all but six returned to their former occupation. Neither the initial fracture type nor the treatment had any apparent bearing on subsequent function; nor was there any correlation between radiographic assessment of the injury and the patient's symptoms. PMID- 3108262 TI - Bone scanning of the foot for unexplained pain. AB - This paper reports the results of bone scans on 78 painful feet. Scanning helped in the diagnosis of persistent foot pain following injury and it enabled stress fractures, fractures of the sesamoids and subtalar arthritis to be diagnosed earlier. It reliably excluded bone infection and was useful as a screening test when radiographs were normal. PMID- 3108263 TI - Reproductive and endocrine gonadal capacity in patients treated with COPP chemotherapy for Hodgkin's disease. AB - Testicular and ovarian functions were assessed in 33 patients with Hodgkin's disease 1 to 17 years after cessation of COPP chemotherapy with cyclophosphamide, vincristine, procarbazine, prednisone. Diagnostic procedures consisted of hormone measurements, interviews, and semen analyses. In women serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), 17 beta-estradiol, progesterone, prolactin, and in men FSH, LH, 17 beta-estradiol, testosterone, and prolactin were determined. Semen analyses were performed in all men. Information concerning pregnancies, pregnancy outcome, future fertility wishes, sexual functions, menstrual pattern, and incidence of premature menopausal symptoms was ascertained by interview and questionnaire. Nineteen of 19 (100%) men showed elevated serum FSH levels between 715 and 1910 (median 1095) ng/ml and azoospermia, 1 to 11 years after therapy. Serum levels of testosterone were within normal limits in 18/19 (95%) of the men, and LH values were normal in all men. Permanent ovarian failure occurred in 8/14 (57%) women, causing infertility and premature menopausal symptoms. The incidence of ovarian failure in women over 24 years was 86% (6/7) versus 28% (2/7) in those under 24 years at the time of treatment. In women receiving estrogen replacement, incidence and severity of these symptoms were significantly reduced. Of 14 women 3 (21%) became pregnant and delivered 5 healthy children after treatment. Our results suggest irreversible sterility and normal Leydig cell function after COPP chemotherapy in all men. Drug-induced ovarian failure was age-related and caused premature menopausal symptoms, detracting from the quality of the patient's life. To reduce premature menopausal symptoms and to prevent adverse cardiovascular and metabolic late sequelae, hormonal replacement is indicated. Pregnancies ending in normal live births can be achieved after COPP chemotherapy in young women. In both men and women, serum FSH and LH levels proved to be feasible markers to determine degree and duration of endocrine and reproductive gonadal injury after chemotherapy. PMID- 3108264 TI - Three-dimensional organization of Drosophila melanogaster interphase nuclei. I. Tissue-specific aspects of polytene nuclear architecture. AB - Interphase chromosome organization in four different Drosophila melanogaster tissues, covering three to four levels of polyteny, has been analyzed. The results are based primarily on three-dimensional reconstructions from unfixed tissues using a computer-based data collection and modeling system. A characteristic organization of chromosomes in each cell type is observed, independent of polyteny, with some packing motifs common to several or all tissues and others tissue-specific. All chromosomes display a right-handed coiling chirality, despite large differences in size and degree of coiling. Conversely, in each cell type, the heterochromatic centromeric regions have a unique structure, tendency to associate, and intranuclear location. The organization of condensed nucleolar chromatin is also tissue-specific. The tightly coiled prothoracic gland chromosomes are arrayed in a similar fashion to the much larger salivary gland chromosomes described previously, having polarized orientations, nonintertwined spatial domains, and close packing of the arms of each autosome, whereas hindgut and especially the unusually straight midgut chromosomes display striking departures from these regularities. Surprisingly, gut chromosomes often appear to be broken in the centric heterochromatin. Severe deformations of midgut nuclei observed during gut contractions in living larvae may account for their unusual properties. Finally, morphometric measurements of chromosome and nuclear dimensions provide insights into chromosome growth and substructure and also suggest an unexpected parallel with diploid chromatin organization. PMID- 3108265 TI - Three-dimensional organization of Drosophila melanogaster interphase nuclei. II. Chromosome spatial organization and gene regulation. AB - In the preceding article we compared the general organization of polytene chromosomes in four different Drosophila melanogaster cell types. Here we describe experiments aimed at testing for a potential role of three-dimensional chromosome folding and positioning in modulating gene expression and examining specific chromosome interactions with different nuclear structures. By charting the configurations of salivary gland chromosomes as the cells undergo functional changes, it is shown that loci are not repositioned within the nucleus when the pattern of transcription changes. Heterologous loci show no evidence of specific physical interactions with one another in any of the cell types. However, a specific subset of chromosomal loci is attached to the nuclear envelope, and this subset is extremely similar in at least two tissues. In contrast, no specific interactions between any locus and the nucleolus are found, but the base of the X chromosome, containing the nucleolar organizer, is closely linked to this organelle. These results are used to evaluate models of gene regulation that involve the specific intranuclear positioning of gene sequences. Finally, data are presented on an unusual class of nuclear envelope structures, filled with large, electron-dense particles, that are usually associated with chromosomes. PMID- 3108267 TI - Bombesin induction of c-fos and c-myc proto-oncogenes in Swiss 3T3 cells: significance for the mitogenic response. AB - Bombesin is a potent mitogen for Swiss 3T3 cells and acts synergistically with insulin and other growth factors. We show here that addition of bombesin to quiescent Swiss 3T3 cells causes a striking increase in the levels of c-fos and c myc mRNAs. Enhanced expression of c-fos (122 +/- 14-fold) occurred within minutes of peptide addition followed by increased expression of c-myc (82 +/- 16-fold). The concentrations of peptide required for half-maximal increase in the levels of c-fos and c-myc mRNAs were 1.0 and 0.9 nM, respectively. The peptide [D-Arg1, D Pro2, D-Trp7,9, Leu11] substance P which inhibits the binding of bombesin to its receptor and bombesin-stimulated DNA synthesis in Swiss 3T3 cells blocked the increase in c-fos and c-myc mRNA levels promoted by bombesin. Down-regulation of protein kinase C by long-term exposure to phorbol esters prevented c-fos and c myc induction by bombesin. This and other results indicate that the induction of these proto-oncogenes by bombesin could be mediated by the coordinated effects of protein kinase C activation and Ca2+ mobilization. The marked synergistic effect between bombesin and insulin was used to assess whether the increase in the induction of c-fos and c-myc is an obligatory event in cell activation. In the presence of insulin, bombesin stimulated DNA synthesis at subnanomolar concentrations but had only a small effect on c-fos and c-myc mRNA levels. This apparent dissociation of mitogenesis from proto-oncogene induction was even more dramatic in 3T3 cells with down-regulated protein kinase C. In these cells bombesin stimulated DNA synthesis in the presence of insulin but failed to enhance c-fos and c-myc mRNA levels at comparable concentrations. Thus, the induction of c-fos and c-myc may be a necessary step in the mitogenic response initiated by ligands that act through activation of protein kinase C but the expression of these proto-oncogenes may not be an obligatory event in the stimulation of mitogenesis in 3T3 cells by mitogens that utilise other signalling pathways. PMID- 3108266 TI - Biosynthesis and processing of platelet GPIIb-IIIa in human megakaryocytes. AB - Platelet membrane glycoprotein IIb-IIIa forms a calcium-dependent heterodimer and constitutes the fibrinogen receptor on stimulated platelets. GPIIb is a two-chain protein containing disulfide-linked alpha and beta subunits. GPIIIa is a single chain protein. These proteins are synthesized in the bone marrow by megakaryocytes, but the study of their synthesis has been hampered by the difficulty in obtaining enriched population of megakaryocytes in large numbers. To examine the biosynthesis and processing of GPIIb-IIIa, purified human megakaryocytes were isolated from liquid cultures of cryopreserved leukocytes stem cell concentrates from patients with chronic myelogenous leukemia. Immunoprecipitation of [35S]methionine pulse-chase-labeled cell extracts by antibodies specific for the alpha or beta subunits of GPIIb indicated that GPIIb was derived from a precursor of Mr 130,000 that contains the alpha and beta subunits. This precursor was converted to GPIIb with a half-life of 4-5 h. No precursor form of GPIIIa was detected. The glycosylation of GPIIb-IIIa was examined in megakaryocytes by metabolic labeling in the presence of tunicamycin, monensin, or treatment with endoglycosidase H. The polypeptide backbones of the GPIIb and the GPIIIa have molecular masses of 120 and 90 kD, respectively. High mannose oligosaccharides are added to these polypeptide backbones co translationally. The GPIIb precursor is then processed with conversion of high mannose to complex type carbohydrates yielding the mature subunits GPIIb alpha (Mr 116,000) and GPIIb beta (Mr 25,000). No posttranslational processing of GPIIIa was detected. PMID- 3108268 TI - Peripheral nerve tumors in the upper extremity. AB - Peripheral nerve tumors involving the hand and upper extremity are rare. The types of tumors are few and they can usually be suspected on clinical grounds. The hand surgeon should have a knowledge of the diagnostic possibilities and the treatment options. PMID- 3108269 TI - Effect of neonatal 6-hydroxydopamine treatment on experimental vasospasm following a subarachnoid hemorrhage in the rat. AB - Intracisternal injection of blood in the rat produces an angiographically demonstrable biphasic cerebral arterial vasospasm. Systemic 6-hydroxydopamine (6 OHDA) treatment in the neonatal stage, which causes a depletion of noradrenaline (NA) from both sympathetic and central NA-containing nerve fibers, prevents the development of the late spasm phase, while the acute spasm occurs to the same extent as in normal animals. The occurrence of acute spasm can be prevented by lesioning in the mesencephalon of the ascending catecholamine fibers originating in the lower brainstem and projecting to the hypothalamus. It is suggested that 6 OHDA treatment results in the altered spasm pattern via its effect on catecholamine fibers projecting between the medullary A1 and A2 nuclei and the hypothalamus. The occurrence of acute but not late spasm indicates that there is a different pathway underlying the two spasm phases. PMID- 3108270 TI - Cortical vasodilatation produced by vasoactive intestinal polypeptide (VIP) and by physiological stimuli in the cat. AB - In chloralose-urethanized cats, vasoactive intestinal peptide (VIP), applied by superfusion in steady-state concentration (10(-10)-10(-6) M) onto cortical vessels in situ resulted in a rapid concentration-dependent vasodilatation in vessels that were mildly constricted by prostaglandin F2 alpha (PGF2 alpha) (5 X 10(-5) M) or hypocarbia (PaCO2 = 26). The maximum dilatation produced by VIP (10( 6) M) was about 60% over baseline in pial arteries and 40% in pial veins. Blockade of local neuronal activity with tetrodotoxin (TTX) (10(-5) M) had no effect on the VIP-evoked dilation of pial vessels. Activation of the cortex by either direct electrical stimulation or indirectly by stimulation of the mesencephalic reticular formation (MRF) resulted in a rapid dilatation of pial arterioles and venules. The vasodilatory effects of VIP and of cortical activation via direct cortical stimulation were not blocked by phentolamine (10( 4) M), propranolol (10(-4) M), atropine (10(-4) M), or naloxone (10(-4) M), indicating that the stimulated vasodilatation was not mediated by adrenergic, cholinergic, or opiate receptors. The dilatory effects of MRF, but not direct cortical stimulation, were not blocked by TTX. VIP antiserum (1:25) preincubated in cortical cups had no effect on resting vessel diameter, but resulted in a significant, though subtotal, reduction in the vasodilatation elicited by direct cortical and MRF stimulation. Normal rabbit sera or VIP antiserum preincubated with saturating amounts of VIP were ineffective. In similar experiments, pial arteriolar and venular dilation evoked by hypercarbia was not attenuated by cortically applied VIP antisera. These observations suggest that pial dilation evoked by local increases in neuronal activity may be mediated in part by the local release of VIP from intrinsic neurons. Such a substrate would define a close obligatory coupling between local neuronal activation and local perfusion, such that nutritive flow could be enhanced prior to the onset of any metabolic deficit. PMID- 3108271 TI - In vivo studies on intracellular pH, focal flow, and vessel diameter in the cat cerebral cortex: effects of altered CO2 and electrical stimulation. AB - The time course of changes in cortical tissue pH (pHi) and blood flow during cortical seizures in halothane-anesthetized cats was examined. The clearance of the molecular form of umbelliferone (Um) was used to estimate focal cortical blood flow (CBFu), whereas the ratio of the molecular to the ionic form of the molecule was used to concurrently calculate the local pHi. Resting pHi and flow in normocarbic animals was 7.116 +/- 0.008 and 46 +/- 8 ml/100 g/min, respectively. Respiratory induced alterations of PaCO2 over a range of 20-60 torr revealed a correlated change in pHi from 7.39 +/- 0.05 to 7.01 +/- 0.03 and a monotonic increase in the rate of Um clearance (slope 0.89 +/- 0.13 ml/100 g/min/torr). Focal electrical stimulation of the cortex resulted in a rapid vasodilation (50% dilation = 1-3 s) of pial arterioles and venules and an increase in Um clearance. pHi showed no significant change until around 10 s. The maximum fall in pHi occurred by 30-60 s (6.85 +/- 0.054). Longer intervals of stimulation (10 min) resulted in no further decline in pHi, but upon cessation of stimulation. pHi remained acidotic for poststimulation periods up to 10 min, with a mild but statistically significant acidosis being observed at 20 min. The absolute decline in pH observed following stimulation appeared to be closely regulated, as comparable levels following stimulation were observed during hypocarbia and hypercarbia. These observations thus suggest that pHi regulation during intense cortical activation may be considered in three phases: following the onset of activity, an initial acute regulation of pHi at control levels; an intracellular acidosis of around 6.8, which is closely regulated and which can be readily reversed upon termination of stimulation; and during continued stimulation, a change in state where in spite of no further change in pHi, the ability of the cortex to return to control pHi appears to be significantly impaired. PMID- 3108272 TI - The ordeal of a Vietnam veteran. PMID- 3108273 TI - Approaches to chronic headache. PMID- 3108274 TI - Classic heatstroke: a serious challenge for the elderly. PMID- 3108275 TI - Hemolytic anemia with jaundice and ascites. PMID- 3108276 TI - Early diagnosis of congestive heart failure. PMID- 3108277 TI - What bad apples? PMID- 3108278 TI - How lymphocytes kill tumor and other cellular targets. PMID- 3108279 TI - Anaphylactoid reactions to iodinated contrast media. PMID- 3108282 TI - The cruel paradox of AIDS: a letter and a reply. PMID- 3108280 TI - Thrombolysis in acute myocardial infarction. PMID- 3108281 TI - Sudden painless vision loss and retinal artery occlusion. PMID- 3108283 TI - Coma in the elderly: evaluation and treatment. PMID- 3108284 TI - Adenosine deaminase deficiency. PMID- 3108285 TI - Insulin infusion rate. PMID- 3108286 TI - Mitral prolapse and echocardiography. PMID- 3108287 TI - Pacemakers in asymptomatic patients. PMID- 3108288 TI - Intractable gouty arthritis. PMID- 3108289 TI - A reversible cause of progressive renal destruction. PMID- 3108290 TI - Treating cardiac ischemia: pathophysiologic guidelines. PMID- 3108291 TI - Lipoprotein metabolism: hormonal regulation. PMID- 3108292 TI - Abnormal thyroid function in a healthy newborn. PMID- 3108293 TI - Current uses of phlebotomy therapy. PMID- 3108294 TI - World health: a dream deferred. PMID- 3108296 TI - Psychological testing of patients in pain. PMID- 3108295 TI - Bilateral lung infiltrates in a dialysis patient. PMID- 3108297 TI - Conversations with a Chinese editor. PMID- 3108298 TI - Derailed by the availability heuristic. PMID- 3108299 TI - Hemoptysis, large lung 'abscess' in alcoholic man with bad teeth. PMID- 3108300 TI - What kind of AV dissociation? PMID- 3108301 TI - Diuretic mechanisms as a guide to therapy. PMID- 3108303 TI - Cyclic biospecific affinity chromatographic method for the purification of the sex steroid binding protein (SBP): application to the purification of SBP from toad. AB - A novel biospecific affinity chromatographic procedure was developed for the purification of the sex steroid binding protein from Bufo arenarum. A charcoal column connected in series to the affinity column allows the removal of any ligand non-covalently bound to the matrix or released during its storage, thus avoiding the need for exhaustive and prolonged washing procedures. In addition, it is not necessary to remove the endogenous ligand from the starting material and the binding to the affinity column can be monitored to determine the time required to achieve the maximum yield. The advantages are the charcoal adsorption of the ligand "washed" from the affinity column by the protein to be purified and the amplification provided by the cyclic use of the system. The procedure improves the yield from less than 1% (by conventional procedures) to more than 50%. With minor modifications this procedure can be useful for the purification of binding proteins and receptors. PMID- 3108302 TI - Liquid chromatographic assay for constituent disaccharides of hyaluronic acid and chondroitin sulphate isomers. AB - An improved high-performance liquid chromatographic (HPLC) method for unsaturated disaccharides prepared from hyaluronic acid and various chondroitin sulphate and dermatan sulphate isomers was developed, which involves an ion-exchange resin prepared from a sulphonated styrene-divinylbenzene copolymer. The retention times of the individual unsaturated disaccharides were unique and reproducible, the disaccharides appearing in the following order: unsaturated non-sulphated disaccharide derived from hyaluronic acid, then unsaturated 6-sulphated, non sulphated and 4-sulphated disaccharides from chondroitin sulphate isomers. Unsaturated disulphated disaccharide G had a much shorter retention time than the unsaturated non-sulphated disaccharide derived from hyaluronic acid. The contents of these individual unsaturated disaccharides could be determined with similar sensitivities on the basis of their ultraviolet absorbance. Selective and unique retention times and good resolutions were found for various unsaturated disulphated and trisulphated disaccharides. The proposed method can be used to determine various chondroitin sulphate and dermatan sulphate isomers in addition to hyaluronic acid in amounts as small as 100 ng to 8 micrograms. The practicality of this method was verified by its application to the separation and determination of the different types of chondroitin sulphate and dermatan sulphate isomers derived from human arteries in the presence of appreciable amounts of hyaluronic acid. PMID- 3108304 TI - Bromocriptine treatment in adolescent boys with familial tall stature: a pair matched controlled study. AB - Recently, bromocriptine has been proposed as a novel agent for the treatment of excessively tall stature in adolescents. To further test its value, we treated nine boys, aged 10.0-15.4 yr, for 1 yr with bromocriptine (7.5 mg/day). A paradoxical plasma GH response to TRH was demonstrated in four of eight boys before and in five boys after 6 months of bromocriptine treatment. At the onset of therapy, the mean adult height prediction was 202.2 +/- 4.3 (+/- SD) cm (Bayley-Pinneau), 202.1 +/- 4.7 cm (TW Mark II), and 198.6 +/- 5.3 cm (Roche Wainer-Thissen). After 1 yr of therapy, the mean adult height prediction had changed by -4.5 +/- 2.6 cm (Bayley-Pinneau), -3.4 +/- 2.2 cm (TW Mark II), and 2.6 +/- 1.2 cm (Roche-Wainer-Thissen). These reductions were solely due to a decrease in growth velocity and not to an increased skeletal maturation rate. To substantiate these findings, each treated boy was pair-matched with an untreated tall boy so that their chronological and skeletal ages differed by less than 1 yr. After 1 yr of follow-up, height predictions in the treated boys compared with those in the matched control boys gave significantly reduced results with the Bayley-Pinneau and the Roche-Wainer-Thissen, but not with the TW Mark II, method. Because of this discrepancy it is uncertain whether final height in tall boys will really be reduced by treatment with bromocriptine. PMID- 3108305 TI - Subcutaneous administration of gonadotropin-releasing hormone: absorption kinetics and gonadotropin responses. AB - To evaluate the suitability of the sc route for the pulsatile delivery of GnRH, plasma GnRH, LH, and FSH levels were measured by RIA in five women with hypothalamic amenorrhea after sc injection of single doses of 2.5, 5, and 10 micrograms GnRH. The results were compared with those obtained after bolus iv injection of 10 micrograms GnRH. After sc injection, plasma GnRH levels rose to a dose-related maximum after 5-10 min and fell to less than 10% of the peak value by 90 min. The mean plasma disappearance half-time was 24 min (range, 18-30 min). After bolus iv injection, an initial rapid phase of disappearance (t1/2, 2.8 min) was followed by a slower phase (t1/2, 33 min), falling within the 95% confidence intervals for the disappearance half-time after sc administration (12-36 min). The patterns of LH response to sc and iv GnRH were similar, with maximum levels reached between 20 and 30 min after injection, then declining to 50-69% of the peak value by 90 min after sc injection and 61% of the peak value 90 min after iv injection. There was no significant difference between peak LH responses to 10 micrograms iv and sc doses of GnRH [15.2 +/- 2.5 (+/- SEM) vs. 13.2 +/- 2.2 IU/L]. Subcutaneous administration of three consecutive GnRH pulses at 90-min intervals to four women resulted in gonadotropin responses to each GnRH pulse. We conclude that sc GnRH administration results in pulsatile plasma GnRH and gonadotropin responses, the latter resembling those seen after iv GnRH. These results confirm the suitability of the sc route for pulsatile GnRH delivery. PMID- 3108306 TI - [Effect of testosterone on growth hormone (GH) secretory profiles in female rats]. PMID- 3108307 TI - Effects of etomidate on ovarian steroidogenesis. AB - The present study investigated the influence of two i.v. induction agents, etomidate (0.25 mg/kg) and thiopental (4 mg/kg) followed by isofluorane anaesthesia on the venous blood concentrations of prolactin (PRL), follicle stimulating hormone (FSH), 17 beta-oestradiol (E2), progesterone (P), 17OH progesterone (17OH-P) and testosterone (T) in 18 patients during laparoscopy for oocyte aspiration for in-vitro fertilization. A sharp decrease in the plasma concentration of E2 (P less than 0.01), P (P less than 0.01), 17OH-P (P less than 0.01) and T (P less than 0.01) was observed within 10 min after induction of anaesthesia with etomidate, followed by a gradual return to the baseline levels thereafter. No such decrease was noted after the administration of thiopental. These findings suggest that etomidate, which has previously been reported to inhibit adrenocortical steroidogenesis, can also interfere with the endocrine function of the ovary. PMID- 3108308 TI - The effect of progesterone supplementation prior to the induction of ovulation in women treated for in-vitro fertilization. AB - Thirty-one patients superovulated with clomiphene citrate (CC) and human menopausal gonadotrophin (HMG) were given a single injection of 25 mg progesterone (P group) 6 h prior to injection of human chorionic gonadotrophin (HCG). Levels of urinary and plasma luteinizing hormone (LH) were significantly higher (P less than 0.001) immediately prior to HCG in the P group compared with thirty-one control patients who had HCG on the same night. Plasma levels of progesterone remained significantly elevated (P less than 0.02) for 80 h after injection in the P group, thereafter the level was similar to controls. The number of oocytes recovered, fertilized and replaced per patient was identical in both groups. However, four control patients had no embryos replaced due to failed fertilization. It is concluded that in the majority of P patients the timing of ovulation induction by HCG injection was appropriate as an LH surge was elicited thus reflecting a physiological stage of readiness, and elevated plasma progesterone levels around the time of oocyte recovery and in the early luteal phase do not increase the likelihood of the establishment of pregnancy in patients stimulated for in-vitro fertilization and embryo replacement (IVF/ER) with CC and HMG. PMID- 3108309 TI - Identification of Streptococcus faecalis and Streptococcus faecium and susceptibility studies with newly developed antimicrobial agents. AB - Identification and susceptibility studies were performed on 301 blood and urine Streptococcus faecalis and Streptococcus faecium isolates. Strep Trio-Tubes S4, S5, and S3 (Carr-Scarborough Microbiologicals, Inc.) were compared with conventional methods for accuracy and rapidity. Of 282 isolates identified as S. faecalis, 98% were identified by species in 4 h with Trio-Tubes; the same percentage of isolates analyzed by conventional methods were identified in 24 h. All 14 S. faecium isolates (approximately 5% of the total number of isolates) were identified by Trio-Tubes in 24 h. In vitro MIC susceptibility testing of the isolates was performed by the Dynatech 2000 microdilution technique (Dynatech Laboratories, Inc.). Several newly developed antimicrobial agents, including imipenem (a carbapenem) and some of the quinolone drugs, i.e., CI-934, ciprofloxacin, A-56619, A-56620, amifloxacin, norfloxacin, and enoxacin, were tested, as were ampicillin, erythromycin, and vancomycin. Both ampicillin and vancomycin showed good activity against S. faecalis, with MICs for 90% of isolates tested (MIC90S) of 1 and 2 micrograms/ml, respectively; with S. faecium, ampicillin exhibited an MIC90 of 16 micrograms/ml and vancomycin exhibited an MIC90 of 2 micrograms/ml. Of the newer antimicrobial agents, imipenem and CI-934 exhibited the greatest activity against S. faecalis strains, with MIC90S of 2 and 0.5 micrograms/ml, respectively. MBCs against the isolates were determined with CI-934, with 90% of S. faecalis strains showing MBCs of 1 microgram/ml or less. PMID- 3108310 TI - Comparison of the Chinese schema and the International Antigenic Typing System for serotyping Pseudomonas aeruginosa. AB - Twelve strains of Pseudomonas aeruginosa representing 12 serogroups in the serogrouping schema used in the People's Republic of China were compared with serogroups in the International Antigenic Typing System (IATS). The first eight groups originated in the People's Republic of China, and group II appears to have a new major antigen that is not found in the IATS. Groups I, III, IV, V, VI, VII, and VIII correspond to groups 11, 6, 9, 4, 8, 3, and 1, respectively, of the IATS. Groups IX, X, XI, and XII are immunotypes 3, 4, 5, and 1, respectively, of Fisher et al. (M. W. Fisher, H. B. Devlin, and F. J. Gnabasik, J. Bacteriol., 98:835-836, 1969); they exhibited a wide range of serological cross-reactions but correspond mainly to IATS groups 2, 3, 10, and 6, respectively. PMID- 3108311 TI - Media for study of growth kinetics and envelope properties of iron-deprived bacteria. AB - Ion-exchange chromatography was used to remove iron from complex and chemically defined laboratory media. The kinetics of metal cation removal from the media was investigated by using atomic absorption spectrophotometry, and the results indicated that over 90% of the iron could be eliminated from certain complex media by this treatment. The treated medium was used for growth studies in a gram positive and a number of gram-negative organisms that were isolated from infections in humans. High-molecular-weight outer membrane proteins that are known to be induced under iron-depleted growth conditions (iron-regulated membrane proteins) were observed when a number of gram-negative pathogens were cultivated in the treated media. Iron uptake by Staphylococcus aureus varied, depending on the iron content of the medium. PMID- 3108312 TI - beta-Glucosidase in Candida albicans and its application in yeast identification. AB - In this report we attempt to explain the discrepancy between beta-glucosidase (EC 3.2.1.21) activity in Candida albicans as measured by commercial kits and that found in an experimental assay. beta-Glucosidase activity in American and Israeli isolates of C. albicans was evaluated with the API ZYM and YeastIdent systems (Analytab Products) and with experimental biochemical assays. Activity was found with whole cells and cell extracts of isolates from both sources. The greatest beta-glucosidase activity was found at pH 5.0 and with p-nitrophenyl-beta glucopyranoside (PNP-BDG) as the substrate. In assays with beta-naphthyl-beta-D glucopyranoside and 6-bromo-2-naphthyl-beta-D-glucopyranoside (6-Br-2-naphthyl BDG), no enzyme activity was detected in whole cells and only limited activity was found in cell extracts of isolates from both sources. In studies with PNP-BDG at pH 5.0 and 7.5, 29 to 38% less activity was found at both pHs with American whole cells, and minor activity (20%) was found at pH 7.5 with isolates from both sources. Because assays with PNP-BDG in cell extracts of isolates from both sources showed no significant differences in activity, the more limited beta glucosidase activity in American whole cells was most likely due to less efficient transport. Because the API ZYM system uses 6-Br-2-naphthyl-BDG as the substrate and because the substrate is buffered at pH 7.5 in the API YeastIdent kit, both systems appear to be of limited value for the detection of beta glucosidase activity in C. albicans. PMID- 3108313 TI - Immunological characteristics of malaria antibodies in two regions of Madagascar. AB - Antibodies directed against antigens of the asexual blood stages of Plasmodium falciparum were studied in the plasma of 29 individuals infected with P. falciparum and living in two areas of Madagascar. These plasma samples were investigated by four immunological methods: indirect fluorescence, immunoprecipitation of radiolabeled P. falciparum polypeptides, inhibition of the in vitro growth of P. falciparum, and double diffusion in a gelose plate. A multifactorial correspondence analysis of the results obtained for each sample revealed that the nature of several of the antibodies varied according to the age and place of residence of the subjects. In comparison with plasma samples from older individuals, specimens from young children had a higher immunofluorescence titer, immunoprecipitated several additional peptides (90, 110, and 118 kilodaltons), revealed more precipitation lines in the Ouchterlony plate technique, and did not inhibit the in vitro growth of P. falciparum to the same extent. Furthermore, as opposed to plasma samples from individuals living in the high central plateau, plasma samples from individuals living on the east coast of the island inhibited the penetration of erythrocytes by merozoites of one of the two studied P. falciparum strains and preferentially immunoprecipitated low-, rather than high-, molecular-weight peptides. PMID- 3108314 TI - Rapid diagnosis of human Crimean-Congo hemorrhagic fever and detection of the virus in naturally infected ticks. AB - An enzyme-linked immunosorbent assay (ELISA) was developed to detect Crimean Congo hemorrhagic fever (CCHF) virus-specific immunoglobulin M (IgM) in human serum samples. For this test, a heat-inactivated antigen was prepared from the brains of suckling mice infected with CCHF virus. The IgM-capture ELISA proved more sensitive than indirect fluorescence tests for IgM to this virus. A human serum containing high-titer IgM to CCHF virus was used for an antigen-capture ELISA to detect this virus in heat-inactivated suspensions of virus-infected ticks. The antigen-capture ELISA appeared to be as sensitive as virus isolation in suckling mice. The studies described suggest that the IgM-capture ELISA and the antigen-detection ELISA should provide a rapid and sensitive diagnosis of human CCHF virus infection and should be useful in ecologic studies of this virus. PMID- 3108315 TI - Extraoperative cortical functional localization in patients with epilepsy. AB - Functional localization prior to cortical resections for intractable seizures has usually been performed in the operating room in awake patients. Chronically placed subdural electrodes offer the possibility of performing such testing outside of the operating room and without the unavoidable stresses and time limitations of the surgical setting. The use of the technique is reviewed. PMID- 3108316 TI - Paying for hospital care: evolution and implications. PMID- 3108317 TI - Health without wealth? Costa Rica's health system under economic crisis. PMID- 3108318 TI - Role of nicotinamide adenine dinucleotide and adenosine triphosphate in glucocorticoid-induced cytotoxicity in susceptible lymphoid cells. AB - The possibility that corticosteroid cytotoxicity could be mediated by activation of poly(ADP-ribose) polymerase and consequent depletion of NAD and ATP was evaluated in steroid-sensitive S49.1 and steroid-resistant S49.143R mouse lymphoma cells and in lymphocytes from a patient with chronic lymphocytic leukemia. All cell types were shown to have the enzyme poly(ADP-ribose) polymerase and to increase activity in response to DNA strand breaks. Incubation of susceptible cells with 1 microM dexamethasone resulted in DNA strand breaks. Susceptible cells also showed a dose-dependent decrease in NAD and ATP that preceded loss of cell viability. These studies suggest that steroid-induced cytotoxicity in susceptible lymphocytes is due to the presence of DNA strand breaks that activate poly(ADP-ribose) polymerase to a sufficient degree to consume cellular pools of NAD with a consequent depletion of ATP and loss of cell viability. PMID- 3108319 TI - Interaction between lymphocytes and platelets in the synthesis of prostacyclin. AB - To test the hypothesis that prostacyclin (PGI2) is formed via a biochemical interaction between platelets and lymphocytes, we measured eicosanoids by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). A distinct 6 keto-prostaglandin F1 alpha (6KPGF1 alpha) peak was noted when [14C]arachidonic acid ([14C]AA) was added to the mixed cell preparations which was increased by pretreating platelets with 1-benzylimidazole (1-BI). Lymphocytes prelabeled with [14C]AA failed to form 6KPGF1 alpha when stimulated with phytohemagglutinin (PHA) or ionophore A23187. When the prelabeled platelets were suspended together with aspirin-treated lymphocytes and stimulated with ionophore, thrombin, or collagen, a 6KPGF1 alpha peak was detected and enhanced by 1-BI. These results were supported by quantifying the 6KPGF1 alpha content in the HPLC-purified fraction by RIA. Adding prostaglandin H2 (PGH2) directly to lymphocytes led to 6KPGF1 alpha production. Platelet aggregation and release were inhibited by lymphocytes in a dose-related manner. We conclude that lymphocytes possess PGI2 synthase activity which is capable of converting platelet-derived PGH2 into PGI2. PGI2 formed is sufficient to inhibit platelet function. PMID- 3108320 TI - Clinical diversity in glycogenosis type II. Biosynthesis and in situ localization of acid alpha-glucosidase in mutant fibroblasts. AB - The molecular basis of clinical diversity in glycogenosis type II (Pompe's disease) was investigated by comparing the nature of acid alpha-glucosidase deficiency in cultured fibroblasts from 30 patients. Biosynthetic forms of acid alpha-glucosidase with different molecular mass were separated electrophoretically and identified by immunoblotting. Immuno-electron microscopy was employed to determine the intracellular localization of mutant enzyme. Our studies illustrate that maturation of acid alpha-glucosidase is associated with transport to the lysosomes. Deficiency of catalytically active mature enzyme in lysosomes is common to all clinical phenotypes but, in the majority of cases, is more profound in early onset than in late onset forms of the disease. Thus, the results suggest that the clinical course of glycogenosis type II is primarily determined by the amount of functional acid alpha-glucosidase. The role of secondary factors can, however, not be excluded because three adult patients were identified with very low activity and little enzyme in the lysosomes. PMID- 3108321 TI - Aspirin prolongs bleeding time in uremia by a mechanism distinct from platelet cyclooxygenase inhibition. AB - We reported that aspirin (ASA) abnormally prolongs bleeding time (BT) in uremia. The present study was designed to investigate whether the abnormally prolonged post-ASA BT in uremia is due to different ASA pharmacokinetics and bioavailability that might be a consequence of uremic condition, platelet cyclooxygenase is peculiarly sensitive to ASA in uremia, and ASA affects primary hemostasis in uremia by a mechanism independent of cyclooxygenase inhibition. Our results showed that in patients with uremia, but not in normal subjects, ASA markedly prolongs the BT. This effect is transient and depends on the presence of ASA in the blood. The observed differences in ASA kinetic parameters are not an explanation of the exaggerated effect of ASA on primary hemostasis in uremia. The sensitivity of platelet cyclooxygenase to ASA inhibition is comparable in uremics and in normal subjects. The temporal dissociation between ASA-induced prolongation of BT and the effect on platelet thromboxane A2 generation suggests that ASA inhibits platelet function in uremia by a mechanism distinct from cyclooxygenase blocking. This possibility is strengthened by the observation that ibuprofen at a dose that fully inhibits platelet cyclooxygenase activity does not significantly prolong BT. PMID- 3108322 TI - Metabolism of platelet-activating factor in isolated perfused rat lung. AB - The administration of platelet-activating factor (PAF) into the airway system of the lung is known to cause profound effects, yet little is known about the metabolism of this active lipid mediator. 3H-Labeled PAF administered into the airway of isolated rat lungs was rapidly and extensively metabolized. The tissue retained 96% of the administered radiolabel while the perfusate contained 4%. Characterization of the tissue retained lipid indicated metabolism into lyso-PAF (3.3%), phosphatidylcholine (82.3%), neutral lipid (1.7%) and intact PAF (10.2%). Analysis of tissue phosphatidylcholine by mass spectrometric techniques revealed metabolism of PAF to 1-0-hexadecyl-2-arachidonoyl-GPC, which represented 20-23% of the administered radiolabeled hexadecyl-PAF. These findings support the hypothesis that a relationship between PAF and arachidonate metabolism exists at the intact organ level. Autoradiographic analysis of the cellular distribution of the radiolabeled PAF metabolites in the lung tissue indicated labeling of two cell types, the alveolar type II cell and the nonciliated bronchiolar epithelial cell (Clara cell). PMID- 3108324 TI - Rapid introduction of oral feedings to tube-fed patients. AB - Eleven patients on prolonged tube feedings were introduced to oral feedings in a 2- to 3-week inpatient feeding program. All but one patient successfully made the transition to full oral feeding in this period with minimal disruption of family life and parental anxiety. The program depends on proper selection of oral feeding candidates, preparation of the patient prior to hospital admission, and a firm, consistent approach to overcoming the child's resistance to eating food. A case study, overall results of the program, and management steps are described. PMID- 3108323 TI - Human immunodeficiency virus infection down-regulates HLA class II expression and induces differentiation in promonocytic U937 cells. AB - We studied the effect of human immunodeficiency virus (HIV) infection on the surface-marker expression of the human promonocytic cell line U937. U937 cells persistently produced HIV as detected by reverse transcriptase activity in culture supernatant. Expression of HLA class II antigens on U937/HIV cells was decreased 2- to 10-fold, depending on the Mab used. Class II expression of U937/HIV cells increased approximately two-fold by treatment with r-interferon gamma. Whereas noninfected U937 cells expressed moderate amounts of lymphocyte function-associated antigen-1 (LFA-1) (CD11a) and minimal amounts of the C3bi receptor (CD11b) and p150/95 (CD11c), U937/HIV cells expressed moderate amounts of C3bi receptor and p150/95 and showed elevated expression of LFA-1 alpha (CD11a) and -beta (CD18) chains. Expression of these adhesion molecules resulted in strongly enhanced phorbolester-induced aggregation of U937/HIV cells compared with the noninfected U937 cells. In addition, almost all U937/HIV cells, but not noninfected U937 cells, intensely stained for cytoplasmic nonspecific esterase activity. The effects of HIV infection on U937 cells strikingly resemble the effects of differentiation-inducing agents, such as PMA and DMSO, on the U937 phenotype. Our finding suggests that HIV infection, apart from down regulating class II expression, induces differentiation of U937 cells. PMID- 3108325 TI - Opsonisation and phagocytosis of group B meningococci by polymorphonuclear leucocytes: comparison of sulphonamide sensitive and resistant strains. AB - A large proportion of disease caused by sulphonamide resistant strains of group B type 15 meningococci affects patients 10-24 years. In contrast, disease caused by sulphonamide sensitive strains conforms to the usual pattern, and most infection occurs in early childhood. In an attempt to explain this phenomenon possible differences in susceptibility of resistant and sensitive strains to phagocytosis by polymorphonuclear leucocytes were investigated, using radioactively labelled bacteria. In initial experiments a group B resistant strain required higher concentrations of normal human serum and longer opsonisation times for phagocytosis than an ungroupable non-pathogenic meningococcus. Comparison of sulphonamide resistant and sensitive group B meningococci showed that with either heat inactivated serum or agammaglobulinaemic serum, phagocytosis did not occur with any of the strains, whereas if these two sera were used together, phagocytosis was restored to the level seen with normal human serum. Thus both antibody and complement are required for phagocytosis. Furthermore, opsonisation depended on an intact classical pathway of complement for each group B strain. In all the experiments there was no significant difference between the phagocytosis of sulphonamide sensitive and resistant group B strains neither with regard to the efficiency of opsonisation by normal human serum nor the exact requirements for antibody and complement. PMID- 3108326 TI - Value of charcoal media for recovering staphylococci incorporated in mupirocin ointment. AB - The use of charcoal blood agar supported a good recovery of staphylococci incorporated in Mupirocin ointment in a test in vitro system. The efficacy of this medium was particularly emphasised in the recovery of staphylococci damaged by six hours' exposure to Mupirocin. The media will be of value in following the progress of staphylococcal carriage or infection in patients or carriers being treated with topical Mupirocin. PMID- 3108327 TI - Chlamydial and gonococcal antibodies in sera of infertile women with tubal obstruction. AB - Sera from 48 infertile women with tubal pathology and from 77 infertile women with normal fallopian tubes were tested by enzyme linked immunosorbent assay (ELISA) using Chlamydia trachomatis and Neisseria gonorrhoeae antigens. Control sera were obtained from women undergoing abortion, sterilisation, and from women practising barrier contraception. The results of ELISA for antibodies to chlamydiae were in close agreement with results published previously of an immunofluorescence test on these sera. Antibodies to C trachomatis were found in 73% of the infertile women with tubal pathology, significantly more than in any of the control groups. Only a very low prevalence (2-5%) of antibodies to gonococcal pili was found in all groups, except women undergoing abortion (16%). PMID- 3108329 TI - Appendicular schistosomiasis: a cause of clinical acute appendicitis? AB - The role of schistosomes in the pathologenesis of acute appendicitis in an endemic area was investigated. Of 1600 appendicectomies received in our laboratory, 26 showed appendiceal schistosomiasis, which prompted what we believe to be the first detailed histopathological evaluation of all appendices with schistosomal infestation, without prior knowledge of the clinical and operative diagnoses. The results suggest that there are two types of schistosomal appendicitis, each with distinct clinicopathological features and different pathogenetic mechanisms. They could be called obstructive and granulomatous schistosomal acute appendicitis, respectively. PMID- 3108328 TI - Heat treatment for endocrinological investigations on plasma positive for human immunodeficiency virus (HIV). AB - The effects of heat treatment of serum samples on the hormone analyses used in this laboratory were studied. Total T4, testosterone, progesterone, and growth hormone were not systematically affected by heat treatment over the whole range of analyte concentrations studied; for thyroid stimulating hormone, no effect was noted on serum samples with concentrations of less than 10 mU/l. Significant changes occurred in total T3, cortisol, follicle stimulating hormone, luteinizing hormone, and prolactin. It is suggested that with appropriate preliminary study, heat treated plasma samples may be used in endocrinological investigations without adversely affecting the diagnostic validity of the results. PMID- 3108330 TI - Cost effectiveness of routine postmortem histology. AB - In a retrospective study of the records of 160 necropsies it was found that, according to the clinical and gross necropsy findings, no clinically important abnormality would have been anticipated in 46% of the tissue samples. The estimated annual cost of processing this material alone was pounds 10,500, including the salary of one full time medical laboratory scientific officer (MLSO). Few of the microscopic findings led to a change in diagnosis. It is suggested that unselected postmortem histology is, for diagnostic purposes, not cost effective. PMID- 3108331 TI - Cell surface expression of beta 2-microglobulin (beta 2m) correlates with stages of differentiation in B cell tumours. AB - Cell surface beta 2-microglobulin (beta 2m) densities of malignant B cells were determined by enzyme immunoassay in 97 cases of immunologically defined lymphoproliferative disease. Absolute beta 2m densities were found to depend on disease category with the lowest levels found on cells from chronic lymphocytic leukaemia (mean = 5.6 ng/10(6) cells, n = 27); atypical chronic lymphocytic leukaemia (mean = 5.9 ng/10(6) cells, n = 8); and prolymphocytoid chronic lymphocytic leukaemia variant (mean = 6.0 ng/10(6) cells, n = 16). beta 2m densities for B non-Hodgkin's lymphoma (n = 14) and B prolymphocytic leukaemia (n = 17) cases were 8.1 and 10.0 ng/10(6) cells, respectively, and the highest densities were found on cells from "late-B cell" tumours (mean = 14.3 ng/10(6) cells). Plasma cells from cases of Ig secreting tumours expressed unexpectedly low beta 2m densities (mean = 9.3 ng/10(6) cells; n = 6). PMID- 3108332 TI - Control of oral anticoagulant treatment by chromogenic prothrombin assay. AB - Doses of oral anticoagulants in 50 patients on long term treatment were easily and satisfactorily monitored over six months by an automated chromogenic assay of prothrombin (CPA). It is suggested that chromogenic assay of one or more of the vitamin K dependent coagulation factors would provide a readily standardised alternative to those conventional tests which depend on human brain derived reagents, now regarded as a biohazard. PMID- 3108334 TI - Spurious increase in plasma potassium concentration and reduction in plasma calcium due to in vitro contamination with liquid potassium edetic acid at phlebotomy. PMID- 3108333 TI - Analysis of latex agglutination test for Clostridium difficile toxin A (D-1) and differentiation between C difficile toxins A and B and latex reactive protein. AB - Virulent toxigenic and avirulent non-toxigenic strains of Clostridium difficile gave a positive result in the latex agglutination test (LAT) for C difficile toxin A (D-1). Similar concentrations of latex agglutinating antigen were produced by these strains in vivo. Positive reactions were also given by C sporogenes, proteolytic C botulinum Types A, B, and A/F, and Bacteroides assaccharolyticus. The latex agglutinating antigen was denatured by boiling for 10 minutes, but not by heating at 56 degrees C for 30 minutes. The reaction was abolished by incubation of test material with crude C difficile antitoxin but not with other clostridial antitoxins or specific antitoxin to C difficile toxin A. The latex agglutinating antigen present in C difficile eluted between 0.39% and 0.47% M sodium chloride, and that produced by the other clostridia, between 0.35% and 0.43% M sodium chloride by fast protein liquid chromatography. The latex agglutinating antigen of C difficile was neither cytotoxic nor mouse lethal and was distinct from toxin A and toxin B. In the analysis of faecal specimens from patients with diarrhoea the latex agglutination test correlated better with the presence of C difficile than with toxin B and detected both toxigenic and non toxigenic strains. The latex agglutination test should only be used in the laboratory as an alternative to culture for C difficile and not as a method for the detection of C difficile toxins. PMID- 3108335 TI - Procuring incentives for community health promotion programs. AB - Many community health promotion programs have used incentives to encourage participation and to reward health behavior change. To minimize expenses and to enhance a sense of shared responsibility, a number of projects have turned to community merchants as a source of incentives. This study investigated the relative effectiveness of solicitation methods used to procure incentives from local merchants for community health promotion programs. The effect of setting, i.e. level of urban development, and type of business were also analyzed in terms of procurement rates. Two hundred and eighteen merchants were solicited to gain incentives for two programs. Twenty-four incentives were procured at a total value of $480. Telemarketing and face-to-face contact had similar procurement rates, restaurants were by far the type of business most likely to donate, and rural merchants provided incentives significantly more often than urban merchants, while developing urban area merchants' donation rates were midway in between. Telemarketing was the solicitation method clearly most cost effective. PMID- 3108336 TI - Organization of postcranial kinesthetic projections to the ventrobasal thalamus in raccoons. AB - To determine the presence and organization of kinesthetic, as compared with other mechanosensory projection zones in the thalamus of raccoons, unit-cluster responses to mechanical stimulation of the postcranial body were mapped electrophysiologically in the thalami of 14 raccoons anesthetized with Dial urethane. A distinct zone of kinesthetic projections (from receptive fields in muscles, tendons, and joints) was found in the rostral and dorsal aspects of the mechanosensory projection zone. These projections are somatotopically organized: those from axial structures lie dorsalmost and those from successively more distal limb regions are successively more caudoventral. The kinesthetic forelimb representation is large and lies rostrodorsal to a large central core of cutaneous projections from the forepaw digits. A few scattered kinesthetic projections were found at the caudal edge of the sensory thalamic region. The large, spatially and somatotopically distinct kinesthetic projection zone in the thalamus parallels those seen in the cortex and medulla of raccoons. Similar findings in monkeys, and suggestions from data in cats and humans support the hypothesis of a distinct pathway to the cortex for kinesthetic information in all mammals. PMID- 3108337 TI - Non-von Recklinghausen's neurofibromatosis presenting as hemifacial neurofibromas and contralateral cafe au lait spots. AB - The term neurofibromatosis designates a spectrum of disorders, the most common of which is von Recklinghausen's disease. We describe two patients with forms of neurofibromatosis other than von Recklinghausen's neurofibromatosis, characterized by involvement of half of the face and the contralateral lower extremity. Neither patient had a family history of neurofibromatosis, and a thorough evaluation of both patients failed to reveal evidence of von Recklinghausen's disease. The classification of neurofibromatosis is briefly summarized, with special emphasis placed on the need for a specific diagnosis regarding the type of neurofibromatosis for purposes of estimating prognosis and providing genetic counseling. The relationship between pregnancy and neurofibromatosis is also discussed. PMID- 3108338 TI - Xanthomas in the Watson-Alagille syndrome. AB - The Watson-Alagille syndrome is a distinctive type of congenital cholestasis, in which hepatic ductular hypoplasia is associated with various ocular, bony, and cardiac anomalies, often with a characteristic facies. The prognosis is surprisingly good, and we present a 26-year-old woman with this syndrome in whom intense pruritus and xanthomatosis had been prominent during infancy but had subsequently cleared completely. The recognition of this syndrome in a young child with cholestatic jaundice may obviate the need for a diagnostic laparotomy. PMID- 3108339 TI - Plasma amino acids and milk protein production by cows fed rumen-protected methionine and lysine. AB - Eighteen Holstein cows in midlactation were used to study the effectiveness of encapsulated rumen-protected methionine and rumen-protected lysine to deliver methionine and lysine postruminally. The experimental design was a 2 X 2 factorial, a center point, and a control treatment run in a partially balanced, incomplete block design. Treatments were administered over three periods of 3 wk. Cows were fed a blended diet consisting of corn silage, corn, and soybean meal supplemented with five different amounts of rumen-protected methionine and lysine. The amounts of DL-methionine and L-lysine (g/d), respectively, supplied from the encapsulated rumen-protected preparations for the six treatments were 1) 0, 0; 2) 10.40, 18.00; 3) 4.52, 7.82; 4) 16.28, 7.82; 5) 16.28, 28.18; and 6) 4.52, 28.18. In vitro results indicate that amino acids in both of the encapsulated preparations were 94% stable at a pH (5.4), which simulated the rumen, and 94% released at a pH (2.9), which simulated the abomasal environment. A linear increase of plasma methionine and lysine was observed as the amount of methionine and lysine supplied postruminally increased. The concentrations (microgram/ml) of methionine and lysine in plasma for the six treatments were 1) 2.47, 9.05; 2) 3.73, 11.59; 3) 3.60, 11.86; 4) 6.09, 10.45; 5) 5.28, 13.43; and 6) 3.33, 13.27. Rumen-protected lysine increased feed intake, milk yield, and 4% fat-corrected milk production within the surface treatments but had no effect when compared with the unsupplemented control treatment. Rumen-protected methionine and lysine increased production of milk protein. Lysine appeared to improve the utilization of methionine. PMID- 3108340 TI - A new feeding device for treatment of glycogen storage disease. AB - To facilitate nighttime management of patients with glycogen storage disease, intragastric drip infusions of concentrated solutions of either glucose or dextrins has been recommended. This paper reports a removable maxillary acrylic appliance used successfully as a feeding device. PMID- 3108341 TI - Advanced dental education for the general dentist: a perspective. PMID- 3108342 TI - Treatment of multiple facial neurofibromas with dermabrasion. AB - Three patients with multiple facial neurofibromas were treated by dermabrasion with good cosmetic results. Wound healing was entirely normal and no complications were observed. There was no evidence of accelerated regrowth of tumors during follow-up. PMID- 3108343 TI - Effects of sublethal doses of methoprene on reproduction and longevity of Drosophila melanogaster (Diptera: Drosophilidae). PMID- 3108344 TI - A white paper: the cost benefits of ET nursing in modern health care delivery. PMID- 3108345 TI - Combination of tocainide and quinidine for better tolerance and additive effects in patients with coronary artery disease. AB - The efficacy and tolerance of tocainide used alone and in combination with quinidine were studied in 20 patients with coronary artery disease and frequent (greater than 30/h) ventricular premature complexes. Holter electrocardiographic monitoring was performed at baseline and during therapy with tocainide alone, quinidine alone and a combination of tocainide and quinidine. During single drug therapy, the dose of tocainide was 1,680 +/- 437 mg/day and that of quinidine was 1,340 +/- 235 mg/day. During combination therapy, with smaller doses of tocainide (1,350 +/- 394 mg/day) and quinidine (1,060 +/- 268 mg/day) in many patients, no patient had side effects. At baseline before therapy, the mean ventricular premature complexes/h were 629 +/- 567, couplets/h were 23.9 +/- 29.7 and nonsustained ventricular tachycardias/24 h were 60.5 +/- 152.2. Compared with baseline values (100%), the frequency of ventricular premature complexes was reduced to 33 +/- 44% with quinidine, 39 +/- 30% with tocainide and 10 +/- 16% with combination therapy (p less than 0.01 for combination versus quinidine or tocainide alone; p = NS for quinidine versus tocainide). Individually, an effective regimen (greater than 83% reduction of ventricular premature complexes and abolition of nonsustained ventricular tachycardia) was found in 3 (15%) of 20 patients receiving tocainide alone, in 6 (30%) receiving quinidine alone and in 16 (80%) receiving combination therapy (p less than 0.01 for tocainide versus combination, quinidine versus combination; p = NS for tocainide versus quinidine). Thus, the antiarrhythmic effects of quinidine and tocainide are additive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108347 TI - Incidence of protein calorie malnutrition in the nursing home population. AB - That nutritional parameters change with age is a well-known phenomenon. Physical activity, lean body mass, and metabolic rate all decline with increasing age. There has been little work regarding the nutritional assessment of geriatric nursing home patients to determine their nutritional status and to focus attention on their nutritional needs. The purpose of this study was to assess the nutritional status of the residents of two urban nursing homes. The nutritional status of 227 nursing home residents (mean age 72.2 years) was evaluated using biochemical and anthropometric measurements. Midarm muscle circumference, triceps skinfold thickness, weight, height, serum albumin, serum pre-albumin, serum retinol binding protein, and a complete blood count with differential were obtained. The evaluation of this data indicated that there was a 52% incidence of malnutrition. This can be broken down to: 24% hypoalbuminemic malnutrition, 19% Kwashiokor-Marasmus mix, and 9% Marasmus. Twenty-eight percent of all patients were anergic, and 76% of the patients were anemic. In conclusion, there appears to be far more documentable malnutrition than anticipated or previously reported in this population. PMID- 3108346 TI - Acute coronary artery obstruction in myocardial infarction: overview of thrombolytic therapy. AB - Pump failure, ranging from ventricular dysfunction to acute cardiogenic shock, is now the leading cause of cardiac death. Efforts at temporary mechanical or pharmacologic support of the heart have been largely unsuccessful so that attention is now directed toward prevention of ventricular failure and limitation of myocardial infarct size or even outright prevention of infarction itself. In particular, attention has been refocused on earlier reperfusion efforts with streptokinase. The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function and early mortality was studied in subsets of patients in a randomized trial (Netherlands Interuniversity Cardiology Institute). Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared with conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hours after onset of symptoms indicative of acute myocardial infarction. Of the patients eligible for this detailed analysis, 245 were allocated to thrombolytic therapy and 243 to conventional treatment. Early angiography was preformed in 212 of the 245 patients allocated to thrombolytic therapy. Patency of the infarct related artery was achieved in 181 patients (85%). Enzymatic infarct size, measured from cumulative alpha-hydroxybutyrate dehydrogenase release, was smaller in patients allocated to thrombolytic therapy (median 760 versus 1,179 U/liter in control subjects, p = 0.0001). Left ventricular ejection fraction measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% versus 43% in control subjects, p = 0.0001). Twelve month mortality was lower in patients allocated to thrombolytic therapy (8% versus 16% in the control group, p less than 0.01). In multivariate regression analysis infarct size limitation, improvement of left ventricular ejection fraction and 3 month mortality were predicted by sigma ST, time from onset of symptoms to admission and Killip class at admission. Thrombolysis was most useful in patients admitted within 2 hours after onset of symptoms and in patients with a sigma ST segment of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function or mortality were observed in the subset of patients with sigma ST less than 1.2 mV, admitted 2 to 4 hours after onset of symptoms. PMID- 3108348 TI - Pituitary-hypothalamic response in adolescents with growth failure due to fear of obesity. AB - Nine patients (4F, 5M) aged 12-17 years with "fear of obesity" were studied with a sequential stimulation test utilizing insulin, LRH, TRH, and L-dopa. The comparative groups were nine female with classic anorexia nervosa, five males with undifferentiated nutritional dwarfing, and nine children (1F, 8M) with constitutional growth delay. The serum TSH, glucose, cortisol, somatotropin, prolactin, LH, and FSH were sampled periodically over 2 hours. Basal T3, T4, transferrin, and Somatomedin-C levels were also obtained. The "fear of obesity" patients did not have any pituitary function changes that were unique. These patients, as well as the comparison groups, revealed a delayed TSH response in proportion to the weight deficit which, when expressed as an integrated response, correlated well to the weight deficit for height (P less than 0.001) and to the ability to recover from hypoglycemia (p less than 0.001). The Somatomedin-C level was low and correlated to the T3 level (p less than 0.05) and not correlated to the elevated Somatotropin levels. The pituitary response to combined stimulation in patients with fear of obesity was determined to be a component of the spectrum starting at normal and proceeding to the extreme undernutrition of anorexia nervosa. Pituitary responsiveness, therefore, changes not as a function of the etiology of the malnutrition, but simply as a function of its severity. PMID- 3108349 TI - Efficacy of enteral diets in the prevention of stress-induced gastric erosions in rats. AB - This study compares the prophylactic effects of two different diets and routes of feeding on restraint stress-induced gastric erosions in the rat. Thirty male Sprague-Dawley rats were food-deprived and immobilized for 24 hours using a steel wire mesh. A small silicone tube was placed into either the proximal jejunum or the stomach via a laparotomy. There were three groups of ten rats (five jejunum fed, five stomach-fed), receiving infusions (50 ml/24 h) of: (A) normal saline; (B) free amino acids (Vivonex HN, Norwich Eaton Pharmaceuticals) (60 cal and 0.318 G nitrogen); or (C) a peptide diet, with the nitrogen source as lactalbumin hydrolysate, otherwise identical to B. Gastric acidity was measured every 4 hours. At 24 hours, blood was collected and serum gastrin levels determined. The animals were then sacrificed and the stomachs examined. The results were analyzed using one-way analysis of variance. Fewer gastric erosions and lower serum gastrin levels and gastric acidity were found in animals fed diets B and C, versus animals fed normal saline (p less than 0.05). There was no difference between groups B and C. Our results also show that enteral diets using the jejunal route are better than those using the gastric route in reducing the incidence of stress-induced gastric erosions in rats. PMID- 3108350 TI - Elevation of serum IgG levels and normalization of T4/T8 ratio after hepatitis in a patient with common variable hypogammaglobulinemia. AB - Acute hepatitis infection developed in a 47-year-old male patient with common variable hypogammaglobulinemia as a consequence of plasma transfusion therapy. Coincident with increases in serum transaminase activities indicative of acute hepatitis, serum IgG levels continued to rise to 506 mg/dl. When plasma replacement therapy was stopped, a transient decline in IgG level (to 371 mg/dl) was produced, followed by a sharp increase in IgG to 607 mg/dl. During this period, the patient's T4/T8 ratio, which had been inverted (0.89), exhibited significant normalization to 1.57. Nevertheless, the patient failed to produce specific antibody after immunization with a number of defined antigens. The mechanism whereby this presumed non-A, non-B hepatitis augmented endogenous IgG production in this patient remains unknown but may be related to diminished suppressor T cell activity. The patient's inability to produce specific antibody during this period suggests an underlying defect in one or more lymphocyte subsets involved in either helper T cell activity and/or immunologic memory. PMID- 3108351 TI - Pathophysiology and biochemical mechanisms involved in MPTP-induced parkinsonism. PMID- 3108352 TI - Heterotopic ossification in poststroke hip fracture: a case report. PMID- 3108353 TI - Prevention of oxygen toxicity with superoxide dismutase and catalase in premature lambs. AB - The use of high oxygen concentrations and high mean airway pressures during mechanical ventilation of premature newborn infants with respiratory distress syndrome leads in 20%-30% of the survivors to chronic lung disease. This study explores if exogenous polyethylene glycol conjugated superoxide dismutase (PEG SOD) and catalase (PEG-CAT) mitigate oxygen toxicity in premature lambs with respiratory distress syndrome. Six pairs of premature lambs were delivered by cesarean section and treated by tracheal instillation of 60 mg natural sheep surfactant/kg/body weight. After birth, all lambs were ventilated with 100% oxygen, and one of each pair received a single intravenous injection of 1 million U/kg PEG-CAT and 50,000 U/kg PEG-SOD. At 8 h of age or after respiratory failure was established, the lambs were killed and the lungs were removed intact. Lung damage was assessed by microscopy. The arterial blood gases, pH, and mean airway pressures of the lambs treated with PEG-SOD/PEG-CAT did not differ from those of the controls. Mean PaO2 was greater than 140 mmHg during the first 4 h of the experiments. In the lambs treated with PEG-SOD/PEG-CAT, SOD and CAT levels were very high during the study period and less bronchiolar epithelial damage and lung hemorrhages were found at microscopy. PMID- 3108354 TI - Lack of effect of moderate hypercalcemia on gonadotropin responsiveness to GnRH. AB - To investigate whether moderate exogenous hypercalcemia influences the release of gonadotropin from human gonadotrophs, 6 normal men were given 50 micrograms GnRH iv on two occasions. On one of these occasions GnRH was administered on an iv background infusion of calcium gluconate, on the other GnRH was injected on a background infusion of saline. The calcium infusion induced moderate hypercalcemia (2.7-2.9 mmol/l) during the GnRH stimulation, whereas normocalcemia prevailed (2.1-2.2 mmol/l) when saline was infused over an identical time period. Similar FSH and LH responses to GnRH were obtained during normo- and hypercalcemia. Moreover, serum testosterone (T) and estradiol (E2) remained unchanged by the hypercalcemia. These results imply that moderate exogenous hypercalcemia does not affect hormone release from pituitary gonadotrophs, and fails to affect peripheral cells involved in the production of T and E2. PMID- 3108355 TI - Prolactin unresponsiveness to repeated sulpiride administration in man: recent findings. AB - The mechanism of prolactin (PRL) unresponsiveness to repeated sulpiride (SUL) administration was investigated by means of two experimental protocols. The first one was carried on in seven male volunteers (age 24 to 34 yr) and consisted of two phases separated by a 5-day interval. In both phases 1 mg/kg of SUL was given im and repeated, 24 h later, together with either placebo (PL, 2 ml saline iv) or TRH (200 micrograms iv). 7-10 days later a standard TRH test (200 micrograms iv) was performed. In the second protocol the usual dose (1 mg/Kg im) of SUL was administered alone and, 24 h later, together with 0.1 U/Kg iv of insulin (insulin tolerance test: ITT) to six male volunteers (age 20 to 32 yr). A control standard ITT (0.1 U/Kg iv) was also performed 7-10 days later. Plasma samples for the evaluation of PRL were taken in basal conditions and at regular intervals after each drug administration. In the first protocol, PRL showed a significant increase (peak values at 30 min) after SUL administration in both phases (phase A: 54.8 +/- 5.6 ng/ml, mean +/- SE vs 6.4 +/- 0.3, p less than 0.001. Phase B: 77.5 +/- 3.9 vs 7.0 +/- 0.6, p less than 0.001). Twenty-four h later, PRL levels were still higher than basal and were not affected by the administration of SUL + PL or SUL + TRH. Also in the second protocol, SUL alone induced a significant PRL increase (peak values at 30 min: 47.1 +/- 7.2 vs 4.2 +/- 0.5, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108357 TI - [Lupus erythematosus, circulating anticoagulant and obstetric complications. Apropos of 2 cases]. AB - Systemic lupus erythematosus (SLE) is a disease occurring mostly in women in the childbearing age. We present two cases of pregnancy complicated one by SLE, the other by a "lupus-like" syndrome. In the first case, the fetus suffered from a complete heart block; in the second one, a lupus anticoagulant was discovered in the mother. These two cases are discussed by the light of the literature. PMID- 3108358 TI - Ulnar nerve entrapment due to heterotopic bone formation after a severe burn. AB - Heterotopic bone formation occurs in approximately 2% of severe burns. It occurs most frequently about the elbow and is not related to the location of the burn. Although bony encasement of the ulnar nerve is frequently found, signs and symptoms of ulnar nerve compression due to heterotopic bone have not been previously reported. Early anterior transposition of the nerve is recommended to prevent progressive neurologic loss if compressive symptoms are found in the face of developing heterotopic bone. PMID- 3108356 TI - The GH-releasing hormone (GHRH) test in acromegaly before and after adenomectomy. AB - The GHRH test may represent a new tool in the study of GH dynamics in acromegaly. GH responsiveness to GHRH 1-40 (50 micrograms iv) has been studied in 21 acromegalic patients. Nineteen out of 21 had active disease. Five patients were also studied 1-12 months after neurosurgery. Two apparently cured acromegalics were studied 1-2 yr after surgery. GH secretion has been evaluated in all patients by means of TRH, bromocriptine and insulin hypoglycemia tests, too. GH response to GHRH has also been performed in 14 normal subjects. In acromegaly, GH responses after GHRH (p less than 0.01 vs placebo) were variable. The GH peak ranged from 8 to 445 ng/ml in patients with active disease. Maximum GH increase after GHRH (calculated as peak/basal value ratio) was significantly reduced in acromegaly (2.9 +/- 0.5 ng/ml; mean +/- SE) in comparison to controls (34.1 +/- 10.9 ng/ml; p less than 0.01). No significant differences in GH pattern after GHRH were found between untreated and previously treated patients with active disease. A significant correlation was found between GH basal levels and GH incremental area (p less than 0.05) and between GH basal and peak levels (p less than 0.01) after GHRH. A significant increase in PRL secretion was observed in acromegalic patients after GHRH (p less than 0.01 vs placebo). No discernable variation was found in the other pituitary hormones pattern after the peptide administration. A positive correlation was observed between GH increase after GHRH and insulin hypoglycemia (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108359 TI - Using home equity to finance long-term care. AB - A majority of elderly Americans have the bulk of their assets tied up in the houses they own. Reverse mortgages could tap this home equity, providing loan disbursements without requiring older homeowners to make monthly payments on principal and interest. In this paper we analyze the potential of using home equity to finance long-term care of the elderly, including payments for home care and for long-term care insurance. We first estimate each homeowner's risk of need for care (and risk of institutionalization) and then calculate the degree to which home equity could be used to cover the costs of home care (or of insurance premiums). Special emphasis is placed on those in the highest risk group and on those with the lowest incomes, who often turn out to be the same people. PMID- 3108360 TI - Total parenteral nutrition for patients with respiratory insufficiency. PMID- 3108361 TI - An automated APACHE II scoring system. PMID- 3108362 TI - Lack of response to selection for directional asymmetry in Drosophila melanogaster. AB - Thirty generations of selection for directional asymmetry of eye size was practiced on a stock of D. melanogaster homozygous for the mutant eyeless recessive. There was no obvious response, supporting previous findings that it is difficult to select for right- and left-handed expression of traits in Drosophila. PMID- 3108363 TI - Synteny of SIS and IGLC in owl monkeys. Evidence for karyotype evolution. AB - Two cloned human DNA sequences specific for the SIS and IGLC genes were hybridized with DNAs from panels of rodent-owl monkey somatic cell hybrids. Independent segregation analysis of the related owl monkey DNA sequences for these two genes demonstrated that both the SIS locus and the IGLC locus are localized on owl monkey chromosome 3 of karyotype VI, chromosome 3 of karyotype V, and chromosome 6 of karyotype IV. These syntenic assignments provide genetic evidence for the homology of, at least, a portion of these chromosomes from three owl monkey karyotypes. The findings also help to redetermine the possible chromosome rearrangement that characterized the chromosome complement of owl monkey from Panama and northwestern Colombia with karyotypes II, III, IV, VIII, and IX from other owl monkey populations with karyotypes I, V, VI, VII, X, and XI. PMID- 3108364 TI - Update on thrombolytic therapy. PMID- 3108365 TI - Hemorrhoidectomy in a hemophiliac with factor VIII inhibitors. PMID- 3108366 TI - Subcellular localization of gonadotrophic hormones LH and FSH in frog adenohypophysis using double-staining immunocytochemistry. AB - We applied double post-embedding immunocytochemical methods using specific antibodies against bullfrog (Rana catesbeiana) luteinizing hormone (LH) and follicle-stimulating hormone (FSH) with immunogold staining (5- and 20-nm particles) to determine the subcellular localization of both gonadotropins and to observe their immunostaining patterns in anterior pituitary of the frog Rana pipiens. Results showed that individual gonadotrophs may store either one or both gonadotropins in a given secretory granule and in large globules (lysosomes?). Most gonadotrophs (50-88%) contain both hormones; 12-50% contain only FSH, and only a few (0-7%) contain LH alone. Individual secretory granules, even in cells that contain both hormones, may contain only one or both gonadotropin molecules. Evaluation of the percentage of monohormonal and multihormonal secretory granules revealed that multihormonal secretory granules were the most numerous and that LH monohormonal secretory granules were the least numerous. These results indicate that cellular storage of gonadotropin in amphibian pituitary is similar to that described for mammals, where a single cell type containing both gonadotropins predominates. Variability in hormone content both of cells and of granules in all individuals is consistent with the hypothesis that frog pituitary possesses a single multipotential gonadotroph. PMID- 3108367 TI - Selectively increased production of interferon-gamma by subsets of Lyt-2+ and L3T4+ T cells identified by expression of Pgp-1. PMID- 3108368 TI - Human T cell rosetting is mediated by LFA-3 on autologous erythrocytes. PMID- 3108369 TI - Functional T cell deficits after bone marrow transplantation across minor histocompatibility barriers: effects of graft-vs-host disease on precursor frequency of reactive cells. AB - We have studied T cell responses in mice transplanted with bone marrow from H-2 identical, minor histocompatibility loci-nonidentical donors (B10.BR----CBA) in which graft-vs-host disease is induced by the addition of donor T cells. T cell responses to mitogen were examined both in high density, conventional bulk cultures and by limiting dilution analysis. Long-lasting deficits in the frequency of functional T cells were observed, for both IL 2-producing and cytotoxic cells, in proportion to the severity of the graft-vs-host disease induced. These deficits did not reflect a corresponding loss of Thy-1+ cells nor a loss of function in conventional cultures in mice studied at later times after bone marrow transplantation. These deficits in reactive cells are not completely correctable with IL 2, and provide further insight into the nature of T cell reconstitution of the immune system after bone marrow transplantation. PMID- 3108370 TI - Precursor phenotype of lymphokine-activated killer cells in the mouse. AB - Lymphokine-activated killer (LAK) activity has been proposed to functionally differ from natural killer (NK) activity largely on the basis of a broader target cell spectrum and different kinetics of response to interleukin 2 (IL 2). Similarly, it has been proposed that the precursor cells for LAK activity are phenotypically distinct from NK cells. In most precursor studies, phenotype comparisons have been made between fresh NK cells and LAK cells which have been generated by 3 to 5 days of culture in IL 2. In the present study, we utilized positive selection with monoclonal antibodies to characterize the surface phenotype of precursor cells which give rise to rIL 2-augmented NK activity within 24 hr and to classically generated LAK activity which appears after 3 to 5 days of culture in rIL 2. The results demonstrated that highly purified (93 to 95%) Lyt-2+ or L3T4+ T lymphocytes were unable to generate appreciable amounts of either augmented NK activity or LAK activity when cultured with rIL 2, whereas the highly purified (98%) Lyt-2-, L3T4-, asialo GM1+ lymphocyte subset gave rise to both augmented NK and LAK activities. These findings demonstrate that both augmented NK and LAK activities can arise from precursors expressing the same phenotype. Overall, the results suggest that NK cells in mouse spleen constitute a major precursor component for the generation of LAK activity from that organ. PMID- 3108371 TI - Early effects of HIV on CD4 lymphocytes in vivo. AB - Low circulating CD4 cell numbers and CD4 cell dysfunction are distinguishing features of HIV-mediated disease. The current study delineates the in vivo effects of HIV on distinct functional subsets of CD4 cells in homosexually active men who have been infected with HIV for different lengths of time, and examines the capacity of lymphocytes from these men to proliferate in vitro in response to soluble antigen. Although peripherial blood mononuclear cells from most acquired immune deficiency syndrome (AIDS) patients did not proliferate in response to either tetanus toxoid or Candida albicans, cells from most HIV seropositive men without AIDS, many of whom had been infected for more than 18 mo, responded normally to both. Non-responsiveness in HIV-infected men without AIDS was a late event and was associated with longer duration of infection, lower CD4 cell numbers, and subsequent development of AIDS. A defect in this response was observed in only one of 19 HIV seropositive men whose CD4 levels were greater than 300/mm3, but in eight of 10 with levels less than 300/mm3. The defect could not be attributed to a selective depletion of defined CD4 subpopulations that respond to soluble antigen. Dual-color immunofluorescent flow cytometry indicated that 4B4+, 2H4-, and HB-11- CD4 cells were not lost at a faster rate than other CD4 subsets. PMID- 3108372 TI - Depletion of T-4+ lymphocytes with monoclonal antibody reactivates toxoplasmosis in the central nervous system: a model of superinfection in AIDS. AB - Central nervous system toxoplasmosis causes disability and death in up to 30% of patients with acquired immune deficiency syndrome (AIDS). The source of the toxoplasma infection in these patients and the specific immune deficit that allows for this virulent form of the infection are unknown. By using a mouse model of toxoplasmosis, we found that selective depletion of T-4+ lymphocytes (CD4+ T cells) produces overwhelming infection and death in both acute and chronic toxoplasmosis. However, the pattern of infection is remarkably different in chronically infected mice as compared with acutely infected mice when the mice are depleted of CD4+ T cells. During acute infection loss of the CD4+ T cell population leads to severe systemic infection with only mild disease in the brain. In chronically infected mice depleted of CD4+ T cells, death follows severe CNS damage due to toxoplasma infection with only minor systemic involvement. In chronically infected mice treated with anti-CD4 monoclonal antibody, reactivation of the toxoplasma infection occurs despite high titers of circulating antitoxoplasma antibody. In parallel with these results in mice, CNS toxoplasmosis in AIDS patients may be due to reactivation of infection acquired much earlier in life. PMID- 3108373 TI - Autoimmune effector cells. IX. Inhibition of adoptive transfer of autoimmune encephalomyelitis with a monoclonal antibody specific for interleukin 2 receptors. AB - This study was conducted to determine whether a monoclonal antibody (MAb) specific for rat interleukin 2 receptors (IL 2R) inhibits the activation of effector T cells that adoptively transfer experimental allergic encephalomyelitis (EAE). MAb OX 39 appears to be specific for IL 2R because it binds to concanavalin A-activated, but not resting, rat lymphocytes and inhibits mitogen- and IL 2-induced proliferation of rat spleen cells. Moreover, this MAb inhibits the in vitro activation of effector cells of EAE by myelin basic protein when added to immune donor spleen cell at the start of 72-hr culture or after 24 hr, but not when added after 48 hr of culture. Other studies employed MAb W3/25, which reacts with the rat helper T cell subset and appears to define the rat homolog of the human CD4 marker present on T4-positive cells. MAb W3/25 also blocks in vitro activation of EAE effector cells, and this blocking effect can be abrogated by adding rat T cell growth factor or partially purified IL 2 to the donor spleen cell cultures. T cell growth factor alone is incapable of activating EAE effector cells. These findings are discussed with respect to the role of lymphokines in the generation of autoreactive T cells. PMID- 3108374 TI - Proteins associated with B lymphocyte hyperactivity in New Zealand black mice. AB - New Zealand Black (NZB) mice exhibit polyclonal B cell activation and elevated immunoglobulin production, an abnormality associated with the spontaneous autoimmune disease that affects this strain. To further our understanding of this abnormality of B cell differentiation and maturation, we have employed two dimensional polyacrylamide gel electrophoresis to analyze the proteins synthesized by lymphocytes of several strains. Two proteins were produced by lymphocytes from NZB mice but not those from normal strains. One was a 16 kd protein with a pI of 5.1, and the other was a 27.5 kd protein with a pI of 4.5. The presence of the xid gene on the NZB background suppressed production of both proteins. They were synthesized by spleen cells but not by bone marrow or lymph node cells, and production was restricted to enlarged B lymphocytes. p16 was synthesized by normal mouse strain B cells upon stimulation with LPS. The 27.5 kd protein was shown to be secreted. On the basis of partial amino acid sequence determination of proteins eluted from gels, p27.5 was identified as J chain and p16 as the C terminal fragment of mu-chain. The synthesis of two other proteins, 13 kd and 18 kd in size, was elevated in NZB spleen lymphocytes. The 18 kd protein was identified as translation initiation factor eIf-4D. The increased level of this protein may be related to the upregulation of immunoglobulin synthesis. PMID- 3108376 TI - Synergistic effect of recombinant IL 2 and interferon-gamma on the proliferation of human monoclonal lymphocytes. AB - We studied the effect of interferon-gamma (IFN-gamma) on the proliferation of lymphocytes from 10 B-type chronic lymphocytic leukemia (B-CLL) patients. In no instance did IFN-gamma induce a proliferative response whether used alone or in combination with anti-mu antibody (Ab). This was observed regardless of the responsiveness of a given patient's cells to interleukin 2 (IL 2) and to B cell growth factor (BCGF). In contrast IFN-gamma strongly and reproducibly synergized with IL 2 (but not with BCGF) to support B-CLL proliferation in five of the 10 patients. The effect of IFN-gamma was dose related and could be inhibited by an anti-IFN-gamma monoclonal Ab. A monoclonal Ab toward the IL 2 receptor molecule was also inhibitory. Preincubation with IFN-gamma potentiated the responsiveness of B-CLL to IL 2 in secondary cultures, showing that IFN-gamma exerts its effect before that of IL 2. PMID- 3108375 TI - Lymphokine activation of T4+ T lymphocytes and monocytes. AB - The function of the T4 antigen, a marker for a differentiated T cell subset, is not well understood. Our previous observation that a chemoattractant human lymphokine, lymphocyte chemoattractant factor (LCF), which selectively induces motile responses in unactivated T4+ lymphocytes, led us to investigate whether LCF could also induce T4+ cell activation. Because LCF acts selectively on T4+ cells, we next determined whether the T4 antigen has a function in this LCF induced cellular activation. A T4+ lymphocyte migratory response is induced by divalent anti-T4 antibody, but not by corresponding Fab fragments of the same antibody. Fab fragments of anti-T4 antibody, but not Fab fragments of anti-T3 antibody, block the migratory effect of both LCF and divalent anti-T4. Furthermore, LCF but not divalent anti-T4, evokes the expression of interleukin 2 (IL 2) receptors and HLA-DR antigen on T4+ lymphocytes in 24 hr. These effects are quantitatively similar to those observed by anti-T3 antibody activation. LCF induced IL 2 receptor expression is blocked by co-incubation with anti-T4 antibody and anti-T4 Fab fragments, whereas anti-T3 activation is not inhibitable by anti-T4 Fab fragments. Because cultured monocytes express the T4 antigen, we investigated the action of LCF on cultured monocyte migration and HLA-DR expression. Induction of monocyte migration by LCF and anti-T4 antibody increases proportionally as T4 antigen expression increases in vitro. This enhanced migration is inhibitable by anti-T4 Fab fragments. Monocyte activation, as measured by augmented HLA-DR expression 24 hr after incubation with LCF, but not anti-T4 antibody, is quantitatively similar to the effects of interferon-gamma. Augmented HLA-DR expression is blocked by anti-T4 Fab fragments but not by antibody to interferon-gamma. These studies indicate that LCF interacts with T4+ lymphocytes and monocytes to induce migration and cellular activation. PMID- 3108377 TI - IgE-enhancing activity directly and selectively affects activated B cells: evidence for a human IgE differentiation factor. AB - T cells from highly atopic individuals spontaneously secrete in vitro a factor that specifically induces IgE synthesis from normal human B cells. We investigated the effects of such T cell supernatants derived from atopic individuals (TCSN-A) on functionally distinct B cell subsets to determine at what developmental stage B cells become responsive to this IgE-enhancing activity. B cells from normal and allergic donors were separated into subsets of small resting and large activated cells by density centrifugation or unit gravity sedimentation. When stimulated by TCSN-A, large activated B cells made more IgE than small resting B cells. The difference was as much as 3300% in comparing these subsets from allergic donors. Similarly, resting B cells stimulated by Staphylococcus aureus Cowan I (SAC) made 52 to 125% more IgE in response to TCSN A than unstimulated small resting B cells. However, IgE production from large B cells, already activated in vivo, was not enhanced by the addition of SAC. Notably, the IgE level synthesized by in vivo large activated B cells from allergic persons was markedly greater than that seen with similar cells from normal donors, whereas resting B cells purified from allergic and normal donors produced comparable levels of IgE in response to TCSN-A. These results suggest that this enhancing activity functions as an IgE differentiation factor for activated B cells. This was further confirmed by the effects of TCSN-A on the IgM and IgE-secreting EBV-transformed human B cell line K1D5. TCSN-A specifically enhanced IgE synthesis from these cells; TCSN from normal donors, IL 2, IFN gamma, and BCGF did not. These results confirm that this activity functions as an IgE-specific differentiation factor, directly influencing activated B cells to synthesize IgE. PMID- 3108378 TI - Structural and functional characteristics of the CD3 (T3) molecular complex on human thymocytes. AB - The CD3 (T3) molecular complex is noncovalently associated with the antigen receptor molecule on T cells. The mitogenic properties of anti-CD3 antibodies have suggested that this complex may be the transducer of the antigenic signal to the intracellular environment. In the present investigation, we studied some of the structural and functional characteristics of the CD3 complex on human thymocytes. In 11 specimens tested, we found that anti-CD3 antibodies react with 50 to 76% of the thymocytes. Two-color immunofluorescence analysis revealed that the majority (greater than 50%) of thymocytes express both CD3 and CD1 on their surfaces. The latter is a marker of immature thymocytes. However, a distinct subpopulation comprising 13 to 19% of the total cells displays only CD3, while an approximately equal percentage of cells expresses only CD1. The mitogenic potential of anti-CD3 antibodies on peripheral T cells is dependent on the presence of monocytes. Anti-CD3 antibodies by themselves cannot activate thymocytes, indicating that functionally active monocytes are absent from the thymocyte population. Even the addition of peripheral monocytes does not allow a response of thymocytes to anti-CD3 antibodies. However, when the anti-CD3 antibody 64.1 is added in the presence of exogenous rIL 2, a strong antibody and lymphokine dose-dependent response ensues. Only CD1- CD3+ thymocytes are stimulated by the addition of antibody and IL 2. The mere expression of CD3 on the CD1+ CD3+ subpopulation of thymocytes apparently is not sufficient to render the cells responsive to the signals of anti-CD3 and IL 2. PMID- 3108379 TI - The effect of LPS on expression of the early "competence" genes JE and KC in murine peritoneal macrophages. AB - The expression of early "competence" genes has been examined in murine peritoneal macrophages treated with bacterial lipopolysaccharide (LPS). This set of genes (e.g., c-myc, c-fos, r-fos, JE, and KC) were first described in BALB/c 3T3 cells treated with platelet-derived growth factor. We have previously reported that LPS induces the rapid and transient expression of both c-myc and c-fos in macrophages. In the present report, we present evidence demonstrating that the mRNA for JE and KC are also induced in macrophages after treatment of LPS. The r fos gene was not detectably induced by LPS under the experimental conditions used in this study. The induction of JE and KC were dependent upon the dose of LPS and exhibited different time courses. mRNA for both KC and JE was induced within 30 min from the initiation of treatment. Although mRNA for JE continued to accumulate for up to 24 hr, mRNA for KC was optimally seen after 60 min and had disappeared by 4 hr. c-fos, JE, and KC mRNA were all inducible by a variety of structurally diverse but functionally similar agents (e.g., heat killed Listeria monocytogenes, maleyl-bovine serum albumin, and fucoidan). Interferon-gamma, a potent but functionally distinct stimulus of macrophage activation, did not effect the expression of JE or KC mRNA. The expression of mRNA for c-fos could be readily induced by treatment of macrophages with phorbol myristate acetate (PMA) alone and that for JE by PMA plus the inophore A23187; mRNA for KC was largely unaffected by these agents. These results suggest that expression of the c-fos and JE genes are regulated by products of polyphosphoinositide hydrolysis. The difference between c-fos or JE and KC raises the possibility that LPS may stimulate at least two independent routes of early gene expression. LPS does not promote macrophage proliferative activity alone, and in fact inhibits the proliferative response to the macrophage growth factor colony-stimulating factor 1. Taken together these findings suggest that the products of these genes may function in the acquisition of competence for highly differentiated functions in addition to that for cell division. PMID- 3108380 TI - Clonal and frequency analyses of tumor-infiltrating T lymphocytes from human solid tumors. AB - A limiting dilution analysis (LDA) was used to assess the functional profiles of tumor-infiltrating lymphocytes (TIL) recovered from 15 human solid tumors. The microculture system applied in this study has been shown to allow virtually all normal peripheral blood T lymphocytes (PBL-T) to undergo clonal proliferation and was applied to obtain estimates of the frequency of both proliferating and cytolytic cells among the TIL population. A total of 624 microcultures proliferating in the presence of irradiated allogeneic spleen cells and interleukin 2 (IL 2) were expanded for clonal analysis. These TIL microcultures were assessed for surface antigen phenotype, IL 2 production (helper function) and for their cytolytic capabilities against the human erythroleukemic line K562 (natural killer (NK)-like activity) and P815, a mouse mastocytoma line, in the presence of phytohemagglutinin (PHA), i.e., lectin-dependent cell cytotoxicity (LDCC) which allows the detection of cytolytic activity irrespective of the antigenic specificity of the effector cells. Whenever feasible, cytolytic activity against autologous and allogeneic tumor cells was tested. LDA first demonstrated that the proliferative potential was decreased in T lymphocytes infiltrating human solid tumors (approximately 1 in 50 to 1 in 2 proliferating T lymphocyte precursors (PTL-P) in this series) as compared to normal PBL-T (1 in 2 to 1 in 1 PTL-P). The growth pattern in the titration cultures showed a remarkable agreement with the single-hit Poisson model implying that third party cells are unlikely to be involved in the reduced proliferative potential. Quantitative estimates of functional precursors showed that, in spite of reduced proliferative potential, cytolytic T lymphocyte precursors (CTL-P) against unknown antigens (LDCC-reactive) accounted for a considerable part of the microcultures in many cases. The precursor frequency of T lymphocytes with NK like activity was usually low in situ (with the exception of glioma), whereas it was in the normal range in the patient's autologous PBL-T. In four evaluable cases, quantitative assessment showed that 1 in 200 to 1 in 1000 T lymphocytes from TIL was cytolytic against allogeneic tumor cells, which is in the range of alloreactive cytolytic T lymphocytes (CTL) generated in the mixed lymphocyte culture from normal PBL. Cytolytic activity against autologous target cells could not be quantitatively estimated but out of 88 clones from 4 patients, 3 clones originating from 2 glioma patients showed high lytic values against autologous tumor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3108381 TI - Antigen-driven T cell clones can proliferate in vivo, eradicate disseminated leukemia, and provide specific immunologic memory. AB - The aim of the current study was to determine the ability of antigen-driven cloned helper cell independent cytotoxic T lymphocytes (HITc) to proliferate and to survive in vivo and to mediate tumor therapy. The HITc clone utilized (denoted 1.B6) was specifically cytolytic to FBL-3, a syngeneic Friend virus-induced murine leukemia. Activation in vitro (48 hr) with FBL-3 induced secretion of interleukin 2 (IL 2), expression of IL 2 receptors (IL 2R), and in vitro proliferation. These cells could be "rested" for several weeks without stimulation, which resulted in reduced expression of IL 2R; however, restimulation with antigen resulted in reinduction of IL 2R and proliferation. The ability of cloned HITc to proliferate and to survive in vivo was examined in cyclophosphamide (CY) pretreated donor mice congenic for the Thy-1 gene. Adoptively transferred cloned HITc could be found in large numbers, and were widely distributed in vivo 1 wk after transfer. In tumor therapy, 1.B6 cells when injected into a site of tumor (i.p.) and used as an adjunct to CY were effective against disseminated FBL-3. In this circumstance, cloned 1.B6 cells could be recovered from cured mice 125 days after transfer and were shown to specifically lyse tumor and proliferate in vitro in response to FBL-3. Thus as an adjunct to CY, tumor-specific cloned HITc are capable of eradicating disseminated leukemia, persisting long-term in vivo, and providing specific immunologic memory. PMID- 3108382 TI - Human T cells targeted with anti-T3 cross-linked to antitumor antibody prevent tumor growth in nude mice. AB - Human peripheral blood T cells were tested for the ability to prevent tumor growth in nude mice when targeted with anti-T3 cross-linked to antitumor antibodies. LS174T human colon adenocarcinoma cells were mixed with human PBL coated either with anti-T3 (Fab) cross-linked to 315F6 (Fab) (an antitumor monoclonal antibody) or with no antibody, and were injected subcutaneously into nude mice. Tumor growth was totally inhibited at effector to target (E:T) ratios of 7.0:1 and 2.1:1, and was partially inhibited at 0.7:1 with antibody-coated PBL, but was not inhibited by uncoated PBL. T cell-mediated protection against tumor growth occurred when an antitumor was physically cross-linked to anti-T3. Neither a mixture of unlinked anti-T3 and antitumor antibodies nor anti-human MHC class I cross-linked to antitumor antibody prevented tumor growth. Whereas in vitro cytotoxicity was mediated exclusively by T8+ cells and was augmented by brief exposure of effector cells to IL 2, tumor neutralization in vivo was mediated by both T4+ and T8+ cells and was not significantly stimulated by prior exposure of the cells to IL 2. We conclude that human T cells, when targeted with appropriate antibody heteroaggregates, can specifically inhibit tumor growth at low E:T ratios, and that cells mediating tumor neutralization in vivo may differ from those mediating cytotoxicity in vitro. PMID- 3108383 TI - Frequency analysis of class I MHC-reactive Lyt-2+ and class II MHC-reactive L3T4+ IL 2-secreting T lymphocytes. AB - The reactivity of Lyt-2+ or L3T4+ T cells stimulated with either mutant class I or class II MHC alloantigens was studied. Whereas stimulation with class I MHC antigens induced only Lyt-2+ T cells to proliferate and to secrete IL 2, stimulation with class II MHC alloantigens induced L3T4+ but not Lyt-2+ T cells. When the frequencies of precursors of IL 2-secreting T lymphocytes (IL 2TL-p) were determined by limiting dilution analyses, class I MHC-reactive Lyt-2+ T cells displayed frequencies (f = 1/200) as high in magnitude as those within class II MHC-reactive L3T4+ (f = 1/100). Clonally developing IL 2TL of either T cell subset were antigen-specific, as shown in split-culture experiments. Whereas L3T4+ helper TL could be induced to specific IL 2 secretion over a long time period (days 3 to 9), Lyt-2+ TL showed a marked time optimal on day 4; thereafter, the number of TL colonies inducible to secrete IL 2 decreased steadily. IL 2 production and IL 2TL-p frequencies of unseparated T responder cells were not the numerical superposition of the two individual T cell subsets (Lyt-2+ + L3T4+); the latter finding is likely to reflect regulatory influences of Lyt-2+ T cells on IL 2-secreting L3T4+ T cells. PMID- 3108384 TI - Tumor necrosis factor-alpha enhances cytolytic activity of human natural killer cells. AB - The effect of recombinant tumor necrosis factor-alpha (rTNF alpha) on human natural killer (NK) function was examined. Lysis of both the NK-sensitive K562 erythroleukemia line and the relatively insensitive renal carcinoma line Cur by nonadherent peripheral blood lymphocytes was significantly enhanced as a result of an 18-hr preincubation with either rTNF alpha or recombinant interleukin 2 (rIL 2). When cells were preincubated with rTNF alpha and low doses of rIL 2 (1 to 10 U/ml), marked additional augmentation of lysis of both targets was noted which was greater than that caused by either cytokine alone. Similar results were observed when responses of CD16+ large granular lymphocytes selected with the fluorescence-activated cell sorter after staining with the NK-specific monoclonal antibody Leu-11 were examined, indicating that the action of the cytokines was directly on the cytotoxic cells. Augmentation of tumor cell lysis could not be ascribed to a cytolytic activity of rTNF alpha on the targets, because no combination of rIL 2, rTNF alpha, or interferon-gamma caused lysis of K562 or Cur. By flow cytometric analysis, it was found that expression of IL 2 receptors was induced on purified CD16+ large granular lymphocytes by rTNF alpha alone and to an even greater degree by the combination of rTNF alpha and rIL 2. Additional analysis of the expression of surface antigens and blocking studies with monoclonal antibodies showed that enhanced tumor cell lysis was not caused by the augmentation of leukocyte function-associated antigen-1-mediated effector/target interactions. These data indicate that rTNF alpha alone, or in combination with rIL 2, directly augments NK cytotoxic activity. PMID- 3108385 TI - Interferon-gamma enhances expression of secretory component, the epithelial receptor for polymeric immunoglobulins. AB - Recombinant interferon-gamma (IFN-gamma) increased in a dose-dependent manner the intracellular pool, the membrane expression, and the shedding of secretory component (SC) in human colonic adenocarcinoma cell line (HT-29). A similar dose response relationship was observed when we examined the binding of polymeric IgA to HT-29 cells treated with IFN-gamma, thus reflecting expression of functional SC. Because IFN-gamma is produced by T cells during immune responses, activated T cells may be able to promote the external transport of dimeric IgA and pentameric IgM and thereby enhance the efferent limb of the secretory immune system. This is, therefore, the first observation indicating how the secretory transport capacity may be adjusted to increased local immunoglobulin production. PMID- 3108386 TI - Effect of serotonin (5-HT) and other monoamines on murine macrophages: modulation of interferon-gamma induced phagocytosis. AB - We have previously shown that serotonin (5-HT) suppresses interferon-gamma (IFN gamma)-induced Ia expression. In the present report, we show that 5-HT as well as other monoamines, histamine and dopamine, modulate IFN-gamma-induced phagocytosis in murine bone marrow macrophages. The effect of 5-HT on IFN-gamma-induced phagocytosis varied according to the concentration of IFN-gamma to which the macrophages were exposed. At low concentrations of IFN-gamma, 5-HT augmented phagocytosis, whereas at high concentrations of IFN-gamma, 5-HT suppressed phagocytosis. At both low and high IFN-gamma concentrations the response to 5-HT was dose-related and occurred at physiologic concentrations; the half-maximal effect was 6 X 10(-7) M and 3 X 10(-7) M for low and high IFN-gamma concentrations, respectively. Both histamine and dopamine also augmented IFN gamma (1 U/ml) induced phagocytosis, at half-maximal augmenting concentrations of 7 X 10(-8) M and 4 X 10(-7) M, respectively. The 5-HT effects were blocked by the 5-HT antagonists spiperone, ketanserin, LY53857, mCPP, and PAPP, but not by the histamine antagonists pyrilamine, chlorpheniramine, or cimetidine. Histamine augmentation of IFN-gamma-induced phagocytosis was blocked by the H1 antagonists pyrilamine and chlorpheniramine, but not by the H2 antagonist cimetidine. The dopamine effect was blocked by spiperone and pyrilamine, both of which have been shown to block dopaminergic effects in other systems. This data provides functional evidence that at least part of the modulation of IFN-gamma-induced phagocytosis by 5-HT occurs through a 5-HT receptor-mediated mechanism, and 5-HT, dopamine, and histamine modulate IFN-gamma-induced phagocytosis independently through their respective receptors. PMID- 3108387 TI - Role of a guanine nucleotide regulatory protein in the activation of phospholipase C by different chemoattractants. AB - It is well established that formyl peptide chemoattractants can activate a phospholipase C in leukocytes via a pertussis toxin (PT)-sensitive guanine nucleotide regulatory (G) protein. Whether this pathway is similarly used by chemoattractant receptors as a class has been unclear. We now report that lipid and peptide chemoattractants in direct comparative studies induced similar amounts of initial (less than or equal to 15 sec) inositol trisphosphate (IP3) release in human polymorphonuclear leukocytes, but the response to lipid chemoattractants was more transient. Production of IP3 by all chemotactic factors was inhibited by treatment of the cells with PT, indicating that chemotactic factor receptors as a class are coupled to phospholipase C via a G protein that is a substrate for ADP ribosylation by PT. The peptide and lipid factors had comparable chemotactic activity, which was also inhibitable by PT. However, transient activation of phospholipase C is apparently an insufficient signal for full cellular activation, since the lipid chemotactic factor leukotriene B4 and platelet-activating factor were poor stimuli for O2- production and lysosomal enzyme secretion compared with N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu Phe). Nonetheless, treatment with PT inhibited O2- production and enzyme secretion in response to all chemoattractants, but as previously noted, did not affect Ca2+ ionophores, lectins, or phorbol myristate acetate. Formyl peptide and lipid chemotactic factors induced similar levels of Ca2+ mobilization when monitored by Quin 2 or chlortetracycline (CTC) fluorescence. Although these responses to fMet-Leu-Phe were blocked by PT, the Quin 2 and initial CTC response to the lipid factors were only partially susceptible. Thus, the lipid factors apparently utilize an additional PT-resistant mechanism for redistributing intracellular Ca2+. This latter process requires extracellular Ca2+ and may be independent of the PT-sensitive G protein. PMID- 3108388 TI - An IgG monoclonal antibody to group B meningococci cross-reacts with developmentally regulated polysialic acid units of glycoproteins in neural and extraneural tissues. AB - The structurally similar polysialic acid capsules of group B meningococci and Escherichia coli K1 are poor immunogens, and attempts are currently being made to improve their immunogenicity by chemical modifications. An IgG monoclonal antibody to these polysialic acid capsules was used for the study of the presence of structurally similar components in tissue glycoproteins to investigate the reasons for the poor immunogenicity and to evaluate potential dangers in active or passive immunization. By immunoblotting polysialic acid was detected outside the brain in newborn rat kidney, heart, and muscle. It appeared in immunoblots as one component and with similar mobility to the neural cell adhesion molecule N CAM. Specificity studies of the antibody and endosialidase treatment showed that the polysialic acid glycans detected were composed of chains as long as eight sialic acid residues or more. The polysialic acid was not detected in the corresponding tissues of the adult animal. These results indicate that polysialic acid units are developmentally regulated components of both neural and extraneural tissues, and are bound to components with properties similar to a known cell-adhesion molecule. This together with the presence of low amounts of polysialic acid even in the adult brain, suggests potential hazards in vaccination trials and suggested immunotherapy of meningitis caused by group B meningococci or E. coli K1, which should be carefully assessed. PMID- 3108389 TI - Mycobacterial growth inhibition by interferon-gamma-activated bone marrow macrophages and differential susceptibility among strains of Mycobacterium tuberculosis. AB - Growth inhibition of the intracellular bacterial pathogens Mycobacterium bovis and M. tuberculosis by lymphokine-activated murine bone marrow macrophages was studied. Mycobacterial growth was assessed by the uptake of 3H-uracil or by determination of colony-forming units. Stimulation of macrophages with recombinant interferon-gamma (r-IFN-gamma) or with IFN-gamma-containing supernatants from antigen- or mitogen-stimulated T cells markedly reduced growth of M. bovis strain BCG Phipps or M. tuberculosis strain H37Rv. In contrast, M. tuberculosis strain Middelburg proved resistant to lymphokine-stimulated macrophages, suggesting heterogeneous susceptibility toward lymphokine-activated macrophages among different M. tuberculosis strains. Stimulation could be blocked by anti-IFN-gamma antiserum, indicating that IFN-gamma was capable of activating antimycobacterial macrophage functions. Stimulation with r-IFN-gamma and subsequent phagocytosis of M. bovis did not lead to increased chemiluminescence responses by bone marrow macrophages, suggesting that mycobacterial growth inhibition was not paralleled by the release of reactive oxygen metabolites. We conclude that IFN-gamma-mediated macrophage activation represents a major step in acquired resistance against tuberculosis and that evasion from this mechanism contributes to mycobacterial virulence. PMID- 3108390 TI - Functional properties of a rat monoclonal IgE antibody specific for Schistosoma mansoni. AB - A rat monoclonal antibody of IgE isotype (B48-14) raised against Schistosoma mansoni has been generated by the fusion of mesenteric lymph node cells from LOU/M rats immunized with a preparation of adult schistosome worms and IR973F nonsecreting rat myeloma cells. Investigation of the in vitro effector functions of this IgE antibody showed a high level of cytotoxicity against S. mansoni schistosomula in the presence of eosinophils, macrophages, and platelets. A significant level of protection (40 to 60%) against a challenge infection with S. mansoni cercariae was achieved by passive transfer experiment of B48-14 IgE to naive recipient rats. By immunoprecipitation, B48-14 IgE antibodies were shown to react with an antigen of 26 kDa present in excretion-secretion products of schistosomula, previously described as a potential immunogen eliciting a protective IgE response against schistosomiasis. PMID- 3108391 TI - Mechanism of escape of exoerythrocytic forms (EEF) of malaria parasites from the inhibitory effects of interferon-gamma. AB - We have studied the mechanism of inhibition by interferon-gamma (IFN-gamma) of the development of exoerythrocytic forms (EEF) of Plasmodium berghei in the livers of rats. At the time corresponding to the maximum development of EEF (44 hr after injection of sporozoites), the livers of the IFN-gamma-treated rats contained less parasite DNA as compared with controls. Twenty-four to 72 hr later, the livers of both groups of animals were free of parasites; that is, IFN gamma treatment does not delay the development of the EEF. The decrease in parasite DNA observed in the IFN-gamma-treated rats was due to a diminution in the number, but not the size, of EEF. It appears, therefore, that treatment with the lymphokine either destroys the parasites or does not affect their replication. To study the mechanism of resistance to IFN-gamma of a small population of EEF, we subjected the parasites to four cycles of selection by IFN gamma. The parasites from the "selected" and "nonselected" populations were equally susceptible to inhibition by IFN-gamma, indicating that the escape from IFN-gamma activity is not inherited. PMID- 3108392 TI - Structure of the T15 VH gene subfamily: identification of immunoglobulin gene promotor homologies. AB - We have sequenced and analyzed the flanking and coding regions of four closely related mouse VH gene segments referred to as the T15 gene subfamily. We have found that although the sequence homologies between the four members of this family are greatest in the coding region, significant homologies extend into the leader sequences and the flanking regions as well. Sequence comparisons of the promoter regions of other VH gene segments indicate that the octamer promoter sequence is part of a larger conserved sequence that may play an important role in immunoglobulin gene transcription. Analysis of the lambda clones containing the members of this subfamily indicate that despite the close linkage of two of the members, the average number of kilobases of DNA between the germ-line gene segments of this family is likely to be very great. PMID- 3108393 TI - Induction of platelet cytotoxic functions by lymphokines: role of interferon gamma. AB - Antigen- or mitogen-stimulated CD4+/CD- lymphocytes produced factors able to induce normal human platelets into cytotoxic effectors toward the young larvae of Schistosoma mansoni. The neutralization by monoclonal anti-IFN-gamma antibody of the induction of the platelet killer effect, the presence of IFN-gamma in the CD4+/CD8- lymphocyte supernatant, and, finally, the direct inducer effect of recombinant IFN-gamma clearly demonstrated that IFN-gamma was one of the factors responsible for the induction of platelet cytotoxic functions. PMID- 3108394 TI - Destructive and nondestructive patterns of immune rejection of syngeneic intraocular tumors. AB - Two immunogenic, syngeneic murine tumors were used to analyze the immunopathological processes associated with the immune rejection of primary intraocular tumors. Intracameral inoculation of P91 mastocytoma, an immunogenic variant of P815 mastocytoma, into DBA/2 mice resulted in progressive tumor growth for several weeks before immune rejection eradicated the intraocular neoplasm. The histopathologic characteristics of the tumor rejection included: a) destruction of the vascular endothelium of the microvasculature feeding the tumor; b) ischemic bulk necrosis; c) extensive innocent bystander damage to normal ocular structures; and d) absence of direct inflammatory cell-to-tumor cell contact. Thus, the immunopathological features resembled a delayed-type hypersensitivity (DTH) lesion. A second intraocular tumor model was similarly studied. UV5C25 fibrosarcoma grew slowly in the eyes of syngeneic BALB/c hosts. In sharp contrast to P91 tumors, a mononuclear cellular infiltrate was prominent within the tumor. After 5 wk, the intraocular tumors were completely rejected without detectable damage to normal ocular structures. The rejection of UV5C25 tumors did not produce scar tissue, damage to vascular endothelium, bulk necrosis, or atrophy of the globe. Although tumor-specific cytotoxic T lymphocytes (CTL) and DTH responses were readily detected, there was no histological evidence for DTH-mediated tumor rejection. Moreover, in situ immunoperoxidase staining indicated that the majority of the infiltrating lymphocytes were CTL, based on their characteristic phenotype: Thy-1+, Lyt-2+. Furthermore, the growth of UV5C25 fibrosarcoma in athymic, natural killer (NK) cell competent BALB/c nude mice demonstrated progressive tumor growth without infiltrating host cells. Collectively, the results indicate that immunogenic intraocular tumors can undergo strikingly different patterns of immune rejection with profoundly different pathological consequences. In one case (P91), tumor rejection occurs by a process that strongly resembles DTH and produces extensive nonspecific damage to normal tissues, resulting in irrevocable loss of vision. In contrast, the second intraocular tumor undergoes an immune rejection that is characterized by precision and a notable absence of damage to normal ocular tissues. The weight of evidence presented here strongly supports the hypothesis that the latter form of tumor rejection is mediated by CTL. Thus, the immunologic pathway invoked for tumor rejection in the eye has a profound effect on the fate of this delicate organ and the preservation of vision. PMID- 3108395 TI - B cell stimulatory factor-1 (interleukin 4) activates macrophages for increased tumoricidal activity and expression of Ia antigens. AB - Macrophages are activated by lymphokines (LK) to kill tumor cell and microbial targets. Interferon-gamma (IFN) is the major LK activity in conventional, antigen or mitogen-stimulated spleen cell culture fluids for induction of these macrophage effector functions. In view of the recent demonstration that murine macrophage-like cell lines have receptors for B cell stimulatory factor 1/interleukin 4 (BSF-1), a possible role for BSF-1 in regulation of macrophage function was considered. In this communication, thioglycollate-elicited murine peritoneal macrophages were shown to express about 2300 high affinity (Ka approximately 2 X 10(10) M-1) BSF-1 receptors/cell. Peritoneal macrophages treated with purified, T cell-derived BSF-1 developed potent tumoricidal activity against fibrosarcoma target cells. The concentration of BSF-1 that induced 50% of maximal tumor cytotoxicity was 38 +/- 4 U/ml for seven experiments; similar dose responses were observed with recombinant BSF-1. That BSF-1 dose-responses for induction of macrophage-mediated tumor cytotoxicity were not affected by 5 micrograms/ml polymyxin B suggested that contaminant endotoxins played little or no role in cytotoxic activity. BSF-1 alone (less than or equal to 500 U/ml) was not directly toxic to tumor cells or macrophages. Macrophage tumoricidal activity induced by BSF-1 but not by IFN was inhibited greater than or equal to 90% with monoclonal anti-BSF-1 antibody. BSF-1 induced Ia antigen expression on peritoneal macrophages and increased (twofold to threefold) FcR(II)-dependent binding of murine IgG immune complexes to bone marrow-derived macrophages (greater than 98% macrophages). Based on these findings, it was concluded that BSF-1 is a potent macrophage activation factor. PMID- 3108396 TI - Interaction between cytokines and 8-mercaptoguanosine in humoral immunity: synergy with interferon. AB - In previous studies it has been demonstrated that a T cell-like differentiation signal is transmitted by C8-substituted guanine ribonucleosides such as 8 mercaptoguanosine (8MGuo) to antigen-stimulated B cells. A large subset of potentially reactive B cells remains unresponsive to antigen even in the presence of signals provided by these nucleosides except when this signal is preceded by a soluble activity present in mixed lymphocyte culture supernatants. Studies with purified preparations of interleukin (IL)-1, IL-2, IL-3, granulocyte-macrophage colony stimulating factor, B cell stimulatory factor 1 (IL-4), and B cell growth factor II (IL-5) indicated that none of these activities is capable of synergizing with 8MGuo to augment B cell responsiveness to antigen. Therefore, supernatants from a number of cloned cell lines were examined for activity that could synergize with 8MGuo, in order to determine the cellular source of this activity. Soluble products secreted by cloned 24/G1 T cells act synergistically with 8MGuo to evoke enhanced antibody responses to specific antigen in populations of purified B cells. Because concanavalin (Con) A-activated 24/G1 cells produce large quantities of interferon-gamma (IFN-gamma), the possibility that interferons might mediate synergy with 8MGuo was investigated. Purified murine IFN-gamma is unable to interact synergistically with 8MGuo; moreover, treatment of active 24/G1 supernatants with monoclonal anti-IFN-gamma antibodies or at pH 2 fails to abrogate their ability to synergize. In contrast to IFN gamma, when B cells were supplemented with either IFN-alpha or IFN-beta, antigen dependent synergy with 8MGuo was observed. However, abrogation of IFN-alpha and IFN-beta activity with specific antibodies fails to interfere with synergy between 8MGuo and mixed lymphocyte culture or Con A supernatants. Therefore, it appears that although IFN-alpha and IFN-beta are not responsible for the synergizing activity present in activated T cell supernatants, they nonetheless represent a previously unrecognized source of synergizing activity. PMID- 3108397 TI - The chemotherapeutic effect of praziquantel against Schistosoma mansoni is dependent on host antibody response. AB - To assess the role of host humoral immune responses in the mechanism of action of praziquantel (PZQ) against Schistosoma mansoni, the efficacy of the drug was compared in infected B cell-depleted (mu-suppressed) vs immunologically intact C3H/HeN mice. We found that PZQ was on the average only 20% as effective in eliminating adult schistosomes from mu-suppressed as compared with control animals. Indeed, in three of four experiments performed, the drug failed to significantly reduce adult worm burdens in the mu-suppressed mice. These results were not due to a delay in parasite death in the infected B cell-depleted animals, because adult worms recovered from these mice as late as 7 wk after chemotherapy were indistinguishable in number and appearance from those recovered from non-drug-treated animals. The efficacy of PZQ against schistosomes in mu suppressed mice was completely restored by passive transfer of immune serum from donor mice infected for 6 wk and partially restored with IgG purified from the same sera. Moreover, IgG as well as IgM antibodies were detected by immunofluorescence on the surface of adult worms recovered from intact mice as early as 1 hr after administration of the drug in vivo. The tubercles of the male worms appeared to be a major site for antibody binding. These results formally demonstrate that the mechanism of action of PZQ, the most important anti schistosomal compound in current use, involves a synergy between the drug and the humoral immune response of the host, and suggest that the relevant effector antibodies act directly against parasite antigens which become exposed on the surface of the worms as a consequence of interaction with the drug. PMID- 3108398 TI - Mitogen-driven B cell proliferation and differentiation are not accompanied by hypermutation of immunoglobulin variable region genes. AB - Hybridomas were constructed from splenic B cells after mitogen stimulation in vitro with lipopolysaccharide and dextran sulfate for 9 to 11 days. Extensive proliferation and differentiation (secretion of IgG isotypes) was evident in these cultures before fusion. Hybridomas that express a VH gene segment whose germ-line sequence is known were isolated, and the nucleotide sequences of these expressed VH genes were determined. A total of 3775 VH nucleotides was analyzed in this way, and only one difference from the germ-line VH sequence was observed. The rate of V gene somatic mutation that has been estimated to occur during antigen-driven immune responses in vivo is 10(-3)/base pair/cell division. Given an estimated value for the number of cell divisions that occurred before hybridoma formation, at least 15 changes from the germ-line VH sequence should have been observed if mutation had been occurring at the in vivo rate during the culture period. Therefore, the data suggest that mitogen-driven B cell proliferation and differentiation are not sufficient to induce the hypermutation of Ig V region genes. PMID- 3108399 TI - Suppressed expression of surface Ia on macrophages by lipopolysaccharide: evidence for regulation at the level of accumulation of mRNA. AB - The surface expression of class II major histocompatibility molecules (immune associated or Ia antigens) is an acquired property of macrophages, essential to their ability to interact effectively with T lymphocytes. Surface expression of Ia is induced by stimulants such as interferon-gamma and is suppressed by agents such as lipopolysaccharide (LPS). Recent studies on several cultured cell lines indicate that interferon-gamma can heighten cellular levels of mRNA encoding Ia, and the level of such mRNA may represent an important regulatory focus for controlling expression of surface Ia. Murine peritoneal macrophages were treated with interferon-gamma and/or LPS and expression of Ia mRNA determined by Northern blot analysis with a probe specific for the murine beta-chain of I-A. mRNA specific for I-A beta was not detectable in explanted macrophages obtained from sites of sterile inflammation but was induced by treatment of purified recombinant interferon-gamma. This effect was dose dependent and was optimal by 24 hr after stimulation. Ia-specific mRNA preceded the surface expression of Ia as monitored by a radioimmunoassay using a monoclonal antibody specific for I-A beta. When a physiologic dose of LPS was added concomitantly with the interferon gamma, the time course of induction if Ia-specific mRNA was not altered, but the amount of such mRNA detected was suppressed 40 to 80%. This effect was dependent on the dose of LPS, and the levels of mRNA correlated closely with subsequent surface expression of Ia. The ability of LPS to suppress both mRNA and cell surface Ia expression required that the suppressive agent be added within 12 hr of the inducing stimulus. This is the time frame during which accumulation of mRNA occurs. Thus the data demonstrates that accumulation of specific mRNA is a major regulatory focus governing expression of Ia both by interferon-gamma and LPS. PMID- 3108400 TI - Induction of macrophage Ia antigen expression by rIFN-gamma and down-regulation by IFN-alpha/beta and dexamethasone are mediated by changes in steady-state levels of Ia mRNA. AB - In previous studies, the induction of Ia antigens on murine peritoneal exudate macrophages by recombinant IFN-gamma (rIFN-gamma) and the antagonism of rIFN gamma-induced Ia expression by the inhibitors IFN-alpha/beta and glucocorticoids have been examined. In this report, these findings have been extended to an analysis of total or cytoplasmic mRNA from macrophage cultures treated with rIFN gamma in the absence or presence of these two inhibitors. Recombinant IFN-gamma induced a 5.7- to 6.5-fold increase in steady-state levels of Ia (A alpha specific) mRNA. Coordinate increases in steady-state mRNA for A beta, and E alpha were observed in response to rIFN-gamma. Maximum induction occurred 24 hr post treatment and required the continued presence of rIFN-gamma. Induction of A alpha specific mRNA was sensitive to the protein synthesis inhibitor cycloheximide. Simultaneous treatment of macrophage cultures with rIFN-gamma and IFN-alpha/beta or the glucocorticoid dexamethasone (DEX) resulted in a significant decrease in steady-state, A alpha-specific mRNA levels compared with treatment with rIFN gamma alone. This analysis suggests that both the induction of Ia expression by rIFN-gamma, and the antagonism of rIFN-gamma-induced Ia gene expression by IFN alpha/beta and DEX, are regulated by cognate changes in Ia mRNA. PMID- 3108401 TI - Identification of cellular mechanisms operational in vivo during the regression of established pulmonary metastases by the systemic administration of high-dose recombinant interleukin 2. AB - The systemic administration of high-dose recombinant IL 2 mediated significant reductions of established 3-day pulmonary micrometastases from both weakly immunogenic and nonimmunogenic sarcomas. However, when treatment with IL 2 was delayed for 10 days after the injection of tumor cells in an attempt to treat grossly visible pulmonary macrometastases, only those established from weakly immunogenic sarcomas remained susceptible. Established 10-day pulmonary nodules from the nonimmunogenic sarcomas became refractory to IL 2 therapy. We utilized selective depletion of lymphocyte subsets in vivo by the systemic administration of specific monoclonal antibodies to cells bearing either the L3T4 or Lyt-2 marker or a heteroantiserum to cells bearing the ASGM-1 glycosphingolipid to identify lymphocytes involved in IL 2-induced tumor regression. Cells with potent lymphokine-activated killer (LAK) activity against fresh tumor targets in vitro were identified in the lungs of IL 2-treated mice. By flow cytometry analysis, the majority of these effector cells were Thy-1+, L3T4-, Lyt-2-, ASGM-1+. Depletion in vivo of ASGM-1+ cells before the onset of IL 2 administration eliminated the successful therapy of 3-day pulmonary metastases from nonimmunogenic sarcomas, with concurrent elimination of LAK cell activity in the lungs. In mice with 3-day pulmonary metastases from weakly immunogenic sarcomas, both Lyt-2+ cells and ASGM-1+ cells were involved in IL 2-mediated tumor regression, but Lyt-2+ cells appeared to be the more potent mediator in the response. Lyt-2+ cells were also involved in the elimination of grossly visible 10-day macrometastases from these weakly immunogenic tumors. Depletion of L3T4+ cells had no effect on tumor regression. Thus, although LAK effectors derived from ASGM-1+ precursors can eliminate pulmonary micrometastases regardless of tumor immunogenicity, Lyt-2+ cells are predominant effectors in the elimination of both pulmonary micro- and macrometastases from weakly immunogenic sarcomas. PMID- 3108402 TI - Interferon-gamma regulates the T cell response to precursor nevi and biologically early melanoma. AB - To examine the potential regulatory role of interferon-gamma in the cellular immune response to melanoma and its precursor lesions, we have tested the capacity of this lymphokine to enhance HLA class II antigen-dependent T lymphocyte blastogenesis, its in vitro production by autologous T cells stimulated by melanoma, and its presence in melanocytic lesions in situ. Cell lines derived from a dysplastic nevus, a radial growth phase primary tumor, a vertical growth phase primary, and metastatic lesions were induced by recombinant interferon-gamma to express increased amounts of HLA class II antigens. Such cells were then examined in radioimmunoassay for expression of HLA-DR antigens and in co-culture for their ability to stimulate proliferation of autologous T cells. Interferon-gamma treatment of melanocytic cells increased their expression of HLA-DR antigens threefold to sixfold. In parallel with these findings, co culture of T cells with interferon-treated cells of a dysplastic nevus and a radial phase melanoma led to augmented T cell incorporation of tritiated thymidine, and this stimulation was inhibited with a monoclonal antibody to HLA DR antigens. Despite augmented expression of HLA class II antigens (HLA-DR, -DQ, and -DP), vertical growth phase and metastatic melanoma cells failed to stimulate autologous T cells. When T cells were co-cultured with stimulating melanoma cells, culture supernatants contained significantly increased amounts of interferon-gamma (12 U/ml) in comparison with supernatants of T cells alone (4 U/ml). No interferon was detectable in cultures of melanoma cells alone. To link these in vitro phenomena to in situ events, we used murine monoclonal antibodies to interferon-gamma, the interleukin 2 receptor, and HLA-DR antigens in an immunoperoxidase system to detect interferon production and lymphocyte activation in frozen sections of lesions representative of melanocytic tumor progression. In these studies, precursor dysplastic nevi and radial phase melanomas contained the highest numbers of activated lymphocytes and stained positively for interferon gamma. These results suggest that interferon-gamma plays a central role in the regulation of the cellular immune response to melanoma. It is produced by T cells, likely activated by tumor antigens seen in the context of HLA class II antigens. In turn, interferon-gamma production enhances expression of HLA class II antigens by melanoma and precursor cells, and such enhancement is associated with additional T cell activation in a positive feed-back loop. PMID- 3108403 TI - Large granular lymphocytes from SCID horses develop potent cytotoxic activity after treatment with human recombinant interleukin 2. AB - Peripheral blood mononuclear cells from foals with hereditary severe combined immunodeficiency (SCID) have morphologic characteristics of large granular lymphocytes (LGL). Attempts to demonstrate cytotoxic activity were without success unless the LGL were incubated with 100 U of human recombinant interleukin 2 (rIL 2)/ml for 24 hr. With rIL 2 incubation, low effector to target ratios (10:1) consistently yielded high levels of cytotoxic activity (30 to 50%) in a standard 4-hr 51Cr-release assay using YAC-1 lymphoma or K562 erythroleukemia cell lines as targets. Monoclonal antibody EqT12 reacted with a large percentage of these cells, and the level of cytotoxic activity was directly correlated to the percentage of EqT12+ cells in the preparation. In normal horses, the percentage of circulating EqT12+ cells is low (5%), while at the same time, cytotoxic activity is not usually detectable even with rIL 2 incubation. In contrast, the percentage of EqT12+ cells in blood of SCID horses is high (up to 40%), as is the IL 2-inducible cytotoxic activity. These results indicate that cytotoxic cells with morphologic and functional characteristics of natural killer cells are produced by horses with SCID. PMID- 3108404 TI - Differential mRNA responses in human macrophages activated by interferon-gamma and muramyl dipeptide. PMID- 3108405 TI - A fish oil diet inhibits amyloid P component (AP) acute phase responses in arthritis susceptible mice. AB - Amyloid P component (AP) bears close homology with C-reactive protein and behaves as an acute phase reactant in the plasma of mice but not in man. Our aim was to determine whether AP is influenced by diet, gender, and arthritis severity in a murine model of arthritis. B10.RIII mice were segregated according to gender and diet at 8 wk of age: the source of fat was either corn oil, fish oil, or beef tallow (5% by weight). Four weeks later, each mouse was immunized with 100 micrograms fetal bovine type II collagen, and the incidence and severity of arthritis was noted at weekly intervals. AP was measured by competitive ELISA in plasma taken 5 wk and 15 wk after immunization. AP levels were less in fish oil fed males and females. Under all conditions tested AP levels of females were greater than in males. There was a negative correlation between AP levels and the severity of arthritis. We conclude from these data that although AP levels cannot be used as indices of arthritis severity, there are significant dietary and gender effects on AP concentrations as long as 15 wk after immunization with type II collagen. PMID- 3108406 TI - Lymphocyte activation by phytohaemagglutinin and pokeweed mitogen. Identification of proliferating cells by monoclonal antibodies. AB - Using a two-colour immunofluorescence technique, we have investigated the mitogenic effects of phytohaemagglutinin-M (PHA-M) and of pokeweed nitrogen (PWM) on human lymphocyte subsets. These were identified by CD1, CD3, CD4, CD8, and CD16 monoclonal antibodies, and proliferation was demonstrated by a polyclonal anti-transferrin antibody. Evidence has been obtained for the generation of a population expressing both the CD4 and CD8 antigens simultaneously, in short-term cultures of peripheral blood mononuclear cells in the presence of PWM and of PHA M. PMID- 3108407 TI - Specific selection of lymphocyte subpopulations by avidin-biotin immune rosetting. AB - An immune rosetting method used for positive selection of lymphocyte subpopulations is described that uses biotinylated monoclonal antibody in conjunction with biotinylated red blood cells linked by an avidin bridge. Limiting dilution data are presented that demonstrate the ability of this method to positively select a monoclonal antibody-targeted tumor cell subpopulation. Application of the separation technique to a peripheral blood lymphocyte population resulted in the positive selection of a relatively pure targeted T cell subpopulation and the parallel efficient depletion of the targeted subpopulation from the lymphocyte population. This technique is simple and reproducible, and can be used to efficiently positively select or negatively deplete selected cell subpopulations. PMID- 3108408 TI - Improvement of the in vitro T cell proliferation assay by a modified method that separates the antigen recognition and IL-2-dependent steps. AB - T cell activation is commonly assayed in vitro by measuring the proliferative response of primed cells to an antigenic stimulus. We have modified the conventional form of this assay by dividing up the response into two stages. During the first stage, antigen drives the specific expression of IL-2 receptor expression. This phase is carried out in the presence of homologous mouse serum, in order to reduce non-specific responses to a minimum. During the second phase, proliferation of these activated T cells is driven by the addition of excess exogenous IL-2. This modified form of proliferation assay significantly increased the signal to noise ratio which can be attained, and is of particular value when looking at the T cell response to weak (e.g., cross-reactive) antigens, or low concentrations of antigen. PMID- 3108409 TI - Rhinocerebral mucormycosis. PMID- 3108410 TI - Distribution of ABO and Rh blood groups in Coimbatore district of Tamil Nadu. PMID- 3108411 TI - Epidemiological features of acute viral hepatitis among the Israeli Defence Forces, 1977-83. AB - High morbidity rates of non-B hepatitis in the Israeli Defence Forces has stimulated efforts towards its prevention. This paper analyses morbidity over a period of 7 years since a programme of pre-exposure prophylaxis with human normal immunoglobulin began. Among 1480 cases studied, about 5% were of hepatitis B. In 360 patients further investigated 11% of illnesses were caused by hepatitis non-A non-B viruses; the remainder by hepatitis A virus. Females comprised about 15% of all three groups. Ethnic origin, social class and education were similar in all those with hepatitis A and non-A non-B hepatitis. This was not so for hepatitis B. None of those with hepatitis B gave a history of former blood transfusions or illicit use of drugs. The importance of risk groups and mode of transmission of the various hepatitis viruses is discussed. PMID- 3108412 TI - Effect of mupirocin on the growth and lifespan of human fibroblasts. AB - We have examined the effect of the antibiotic mupirocin on the growth and proliferative lifespan of human fibroblasts. Human embryonic lung fibroblasts were grown in Dulbecco's minimal essential medium, containing 10% fetal bovine serum and various concentrations of mupirocin ranging from 0.5-756 micrograms/ml. There is little difference in the rate of exponential growth and the final saturation density reached between control cultures and those grown in 0.5 microgram, 72 micrograms, or 76 micrograms/ml mupirocin. Growth was retarded or inhibited in cultures containing 650-750 micrograms/ml mupirocin. The proliferative lifespan of adult skin fibroblasts was examined in cultures serially subcultivated in medium containing either 7 micrograms/ml or 100 micrograms/ml mupirocin. Cultures incubated in these concentrations of mupirocin were capable of reaching their full proliferative potential. This study shows that the growth and proliferative lifespan of human fibroblasts is unaltered in the presence of at least 100 micrograms/ml mupirocin although growth of human fibroblasts is inhibited by 700 micrograms/ml mupirocin. These observations suggest that long-term use of low but bactericidal concentrations of mupirocin will not impair growth of fibroblasts in healing wounds. PMID- 3108413 TI - Genotypic analysis of cutaneous T-cell lymphomas. AB - The gene encoding the beta-chain of the T-cell antigen receptor (TCR) has been analyzed for evidence of rearrangement in skin, blood, and lymph node specimens from 23 cases of known or suspected cutaneous T-cell lymphoma (CTCL). Two cutaneous large cell lymphomas, 4 cases of Sezary syndrome, and 5 cases of advanced (tumor) stages of mycosis fungoides showed clonal rearrangement of the TCR beta-chain gene in all samples, including lymph nodes in which histologic examination revealed only dermatopathic lymphadenitis. These results indicate that DNA analysis provides a valuable means for improving the diagnosis of extracutaneous disease in advanced stages of CTCL. In contrast, the gene was in a germline configuration in all samples from 12 patients with plaque stages of mycosis fungoides or suspected early CTCL, suggesting that in these 2 conditions the T-cell proliferation is either polyclonal or contains very few monoclonal (i.e., neoplastic) cells. PMID- 3108414 TI - A comparison of the melanocyte response to narrow band UVA and UVB exposure in vivo. AB - The visible cutaneous pigmentary response to ultraviolet-A (UVA) is immediate and, following sufficient exposure, may persist, whereas ultraviolet-B (UVB) induced pigmentation appears after a delay of several days. We compared the in vivo response of melanocytes to single and multiple exposures of narrow band UVA and UVB irradiation which produced visibly equal increases in pigmentation. Using a xenon-mercury source matched to a monochromator, human volunteers were exposed to 304 (+/- 5) and 365 (+/- 10) nm radiation. Biopsies were performed 1, 7, and 14 days after irradiation. For each biopsy, the number of melanocytes per square millimeter of epidermis was determined using L-3,4-dihydroxyphenylalanine (dopa)- and tyrosine-incubated split epidermal preparations. Vertical sections were also examined. At days 7 and 14, after both 304 and 365 nm radiation, melanocytes were more intensely dopa-positive than in unirradiated controls, and demonstrated enlarged perikarya and a greater number of enlarged dendrites. Following both 304 and 365 nm radiation the number of dopa-positive melanocytes was increased at days 7 and 14 by 44% and 58%, respectively. Tyrosine positivity, an indicator of enhanced tyrosinase activity and increased melanin formation, was absent in controls and at day 1, and became positive in all but one sample at day 7 and day 14. Therefore, one day after UVA exposure, visible pigmentation but not tyrosinase activity was increased. At day 7, the number of tyrosine-positive melanocytes approximately equaled the number of dopa-positive melanocytes. Although UVA and UVB induce different pigmentary responses, their effects on melanocyte number and function were indistinguishable. PMID- 3108415 TI - [Regional coronary outflow and coronary reserve assessed by the thermodilution technique: an experimental study]. AB - Coronary blood flow distribution and coronary flow reserve were experimentally evaluated by the thermodilution technique. Using a special catheter with two external thermistors 5 cm apart, the great cardiac vein (GCV) outflow and coronary sinus (CS) outflow were measured. Coronary inflows in the left anterior descending (LAD) and circumflex (LCX) arteries were measured by electromagnetic flow probes during arterial occlusion or bolus arterial injection of nitroglycerin and dipyridamole injection in a peripheral vein. On the LAD side, the venous flow due to the interventions increased both GCV and CS outflows, while the interventions in the LCX increased CS outflow without significant changes in the GCV flow. LAD inflow and GCV outflow, and LCX inflow and (CS-GCV) flow correlated well, and there were significant close correlations between each inflow and outflow. Coronary reserve in the LAD and LCX was studied in successive 70% and 90% stenoses produced by a calibrated constrictor. Maximal coronary flow was obtained during reactive hyperemic response after coronary artery occlusion. Although there was no significant coronary reserve in the coronary inflow or outflow in the basal state, coronary reserve in the GCV and CS decreased significantly in stenoses of the LAD and LCX. These results suggest that this method allows practical assessment of drainage from the LAD and LCX areas and that stenosis greater than 70% can be estimated from the changes in regional venous outflows. This method may be helpful in evaluating regional coronary hemodynamics clinically. PMID- 3108416 TI - Interferon-gamma potentiation of lipopolysaccharide-induced eicosanoid release from human monocytes. AB - Interferon-gamma (IFN-gamma) can act to potentiate lipopolysaccharide (LPS) stimulated processes in mononuclear phagocytes, including interleukin-1 release and tumoricidal activity. The present investigation examined the capacity of IFN gamma to modulate LPS-stimulated prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) release from counterflow isolated human monocytes. The release of PGE2 and TxB2 was compared for cells incubated with IFN-gamma prior to treatment with LPS and for cells treated simultaneously with IFN-gamma and LPS. Treatment of cells with IFN-gamma prior to stimulation with LPS (10 micrograms/ml, Salmonella typhimurium) resulted in elevated prostaglandin E (by immunoassay) and [3H]PGE2 release from monocytes when compared with LPS-treated cultures. In contrast, IFN gamma pretreatment did not potentiate labeled or immunoreactive TxB2 release from LPS-treated monocytes. IFN-gamma pretreatment without LPS stimulation did not result in elevated eicosanoid release over controls. In addition, continuous treatment of monocytes with both IFN-gamma and LPS did not result in greater release of PGE2 and TxB2 than the summed individual effects of IFN-gamma and LPS. These results indicate that IFN-gamma selectively potentiates LPS-stimulated arachidonic acid conversion to PGE2 and not TxB2 in human monocytes. This effect was observed only for monocytes pretreated with IFN-gamma prior to stimulation with LPS. PMID- 3108417 TI - Induction of interferon production by natural killer cells by organogermanium compound, Ge132. AB - Interferon (IFN)-inducing activity of the organogermanium compound Ge132 in human peripheral mononuclear cells was investigated. By using Percoll discontinuous density gradient centrifugation, peripheral blood nonphagocytic and nonadherent mononuclear cells were divided into the low-and high-density fractions. Natural killer (NK)-enriched low-density fractions, but not the T-cell-enriched high density fractions, showed IFN production by the stimulation of Ge132. The maximal titer of IFN by NK-enriched fractions (F1 + F2) was observed after a 74-h cultivation in the presence of 200 micrograms/ml Ge132. IFN production by the NK enriched fractions was abrogated by treatment of the cells with monoclonal antibody against human NK cells in the presence of complement. The treatment with antiserum-neutralizing human IFN-gamma resulted in a marked reduction, indicating that a major part of IFN was IFN-gamma. These results suggested that Ge132 might possess affinity to NK cells, inducing IFN production by NK cells. PMID- 3108418 TI - Interferon-gamma-induced expression of class I HLA antigens on K-562 cells grown in serum-free medium. AB - Human interferon-gamma (IFN-gamma), encoded in Escherichia coli by recombinant human DNA, induces the expression of HLA antigens in the pluripotent hematopoietic stem cell line K-562 grown in serum-free growth medium. Expression was noted in 90% of the cells within 4 days and there was a high density of expression per cell, as determined by cytofluorography. Upon subculture, the cells rapidly lose their ability to express HLA, indicating that the continued presence of IFN-gamma is necessary for the expression. Reinduction of expression with IFN-gamma occurs in a high percentage of cells (up to 90%), which is comparable to the induction in freshly treated control cells. PMID- 3108420 TI - [Clinical evaluation of the prolactin secreting capacity for the diagnosis of occult hyperprolactinemia]. AB - To clarify the diagnostic criteria of occulted or transient hyperprolactinemia, the resting prolactin level and the prolactin secreting capacity of normal women, which were tested with a 500 micrograms of TRH injection, were compared with those of patients with occulted hyperprolactinemia. Results revealed that: resting levels of prolactin in normal women were 13.4 +/- 4.4 ng/ml (mean +/- S.D.) in the follicular phase and 13.4 +/- 5.6 ng/ml in the luteal phase, which overlapped those of occulted hyperprolactinemia. the prolactin secreting capacity of occulted hyperprolactinemia was significantly greater than that of the normal women. These results indicated that it was impossible to distinguish the occulted hyperprolactinemia from the normal by the measuring the resting prolactin level, but possible by the evaluating the prolactin secreting capacity. If the serum prolactin was more than 150 ng/ml at 15 min. after TRH administration, occulted hyperprolactinemia was strongly suggested. PMID- 3108419 TI - Antibodies to the carboxyl terminus of mouse interferon-gamma neutralize its immunoregulatory and antiviral activities. AB - Antibodies to a synthetic carboxy-terminal peptide (Cys-Ser-Leu-Arg-Lys-Arg-Lys Arg-Ser-Arg-Abu) (gamma-C-TP) of mouse interferon-gamma (MuIFN-gamma) were produced in rabbits. They neutralized the antiviral activity of MuIFN-gamma but not that of MuIFN-alpha/beta or human (Hu) IFN-alpha/beta or -gamma. They also inhibited the IFN-dependent enhancement of natural cytotoxic cells (NCC) and the in vivo plaque-forming cell (PFC) response to sheep red blood cells (SRBC). Thus, our results indicate that polyclonal antibodies specific for the nine carboxy terminal amino acids of MuIFN-gamma can specifically inhibit the antiviral and immunoregulatory activities of this IFN in vitro. In addition, our findings indicate that endogenous production of MuIFN-gamma in vivo plays a role in development of the full antibody response to SRBC surface antigens. PMID- 3108421 TI - [Indication and effect of bromocriptine in euprolactinemic amenorrhea--comparison with clomiphene]. AB - Effect of bromocriptine on induction of ovulation and occurrence of pregnancy was examined in patients with normoprolactinemic ovulatory disturbances. The patients under study (53 in number) were divided into two groups, A and B, depending on the effect clomiphene had on the ovulatory responses and the occurrence of pregnancy. Of the group A, patients (21 in number), who had failed to show any ovulatory response to clomiphene, 8 patients ovulated on bromocriptine alone. Three out of 13 patients who complained of sterility became pregnant. Three out of 8 patients who had not ovulated on bromocriptine therapy alone ovulated on a combination of bromocriptine and clomiphene, and 2 out of these 3 cases became pregnant. Of the group B patients (31 in number), who had failed to become pregnant in spite of ovulatory responses to previous clomiphene therapies, 7 out of 23 became pregnant, who complained of sterility when on bromocriptine alone. Out of 12 cases who had failed to get pregnant on the bromocriptine alone, 2 patients became pregnant on the combination of bromocriptine and clomiphene. These data may indicate that the bromocriptine or the combined therapy of bromocriptine and clomiphene is useful for the treatment of patients with ovulatory disturbances or sterility who do not respond to the clomiphene therapy. PMID- 3108422 TI - [Steroid profiles in patients with amenorrhea during induction of ovulation with HMG]. AB - Serum concentrations of various hormones in seven normal women were measured daily for 5 days before and after ovulation. Steroid levels were also measured in severe amenorrheic patients during the induction of ovulation with HMG-HCG. Blood samples from the patients of II grade amenorrhea were collected on the day when the cervical mucus increased more than 200 mm3 in HMG therapy. HCG was given after the blood samples were obtained. Ovulation was successfully induced in six patients and they were classified as group I. In 8 patients induction of ovulation did not succeed and these patients were classified as group II. Hormone levels including LH, FSH, estradiol (E2), progesterone (P4), 17 alpha OH-P4 (17P4), delta 4 androstenedione (delta 4 A), testosterone (Tes.), pregnenolone (P5), 17 alpha OH-P5 (17P5), DHA, delta 5 androstenediol (delta 5 AD), and 20 alpha OH-P4 (20P4) were measured by specific RIA. The following results were obtained. Steroid levels during normal ovulatory cycle: Levels of E2 (380 +/- 16 pg/ml), P5 (6.9 +/- 4.1 ng/ml), and Tes. (3.3 +/- 1.2 ng/ml) showed a peak on the day before LH surge. A significant increase in P4, 17P5 and 20P4 levels was observed after ovulation. Hormone levels in group I: FSH in group I was significantly higher while LH was lower than that in normal women measured during -1 to -3 days from LH surge. On the other hand, among the steroids measured, significantly low Tes. and high 17P5, and E2 levels were noticed in group I. Comparison of hormone levels between group I and II: FSH and LH levels showed no significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108423 TI - Characterization of transplant generations of primary rat adenocarcinoma and some chemotherapeutic observations. AB - Rats (Wistar) bearing subcutaneous implants of tumor fragment of DMBA-induced tumor were used in this study. Studies have been made of their proliferative characteristics, and their response to Cis-dichlorodiammine platinum (CDDP) has been measured. The transplanted tumor appears to be on homogeneous solid structure throughout all transplant generations, although the primary site is concomitant adenocarcinoma showing both glandular and solid structure. Microangiography showed that the transplanted tumor was more hypervascular than the primary tumor. Compared with the previous reports using the primary autochthonous tumor, the antitumor effect of CDDP is excellent and the histologic effect is observed in all areas of the sectioned surface. The transplanted tumor could provide a useful experimental system for the laboratory study of the chemotherapy of ovarian adenocarcinoma and the possibility of predicting ovarian adenocarcinoma seemed to be great because of the morphological similarity. PMID- 3108424 TI - Cholesterol and steroid levels in human follicular fluids of human menopausal gonadotropin-induced cycles for in vitro fertilization. AB - Fifty-eight follicular fluids (FF) were obtained from 18 women undergoing in vitro fertilization (IVF). Follicular development was induced by human menopausal gonadotropin (hMG) and follicular aspiration was performed 36 hr after an ovulatory dose of human chorionic gonadotropin (hCG). Two stages of oocyte-corona cumulus complexes (OCCCs) morphological maturation was identified in this population: intermediate and mature. FF from which intermediate and mature OCCCs were obtained did not differ in 17 beta-estradiol (E2), progesterone (P), and cholesterol levels. Fifty OCCCs were fertilized and eight were not fertilized. No difference was found in E2, P, and cholesterol levels in those two populations of OCCCs. Forty hours after insemination 50% of the oocytes were at the two-cell stage and 50% were at the three-cell stage. Steroids and cholesterol levels did not differ in FF from which those two groups of embryos originated. A direct correlation was found among the levels of cholesterol, E2, and P in the FF. An inverted ratio of high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) was found in FF compared to serum in 10 women. It is concluded that FF cholesterol levels have no value in predicting follicular maturation. PMID- 3108425 TI - Combination clomiphene citrate/human menopausal gonadotropin stimulation protocols for in vitro fertilization-embryo transfer. AB - Various protocols have been utilized for stimulation of multiple ovarian follicles in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). Previous studies have suggested that the combination of clomiphene citrate (CC) and human menopausal gonadotropins (hMG) is superior to either CC or hMG alone in terms of follicular development, oocyte recovery, and embryo transfer. However, no significant increase in viable pregnancy rates has been reported with any of the protocols. This report examines five different CC/hMG protocols. While differences were seen in terms of serum estradiol response and fertilization rates of mature oocytes among the various protocols, no significant differences were found in terms of follicular development, oocyte recovery, embryo transfer, or pregnancy. The pregnancy rate in IVF-ET appears unaffected by variations in the dose and timing of CC and hMG in a combination protocol. PMID- 3108426 TI - Gonadotropin-induced successful follicular development, oocyte recovery, fertilization, and cleavage of embryos in undiagnosed early pregnancy. PMID- 3108427 TI - Use of GnRH analogues in ovulation induction for in vitro fertilization: benefit of a short administration regimen. PMID- 3108428 TI - Interdepartmental unit for IVF/ET, Serlin-Hakirya Maternity Hospital, Tel Aviv, Israel. PMID- 3108429 TI - Effects of two low-dose oral contraceptives on circulating components of the coagulation and fibrinolytic systems. AB - We studied the effects on plasma levels of coagulation and fibrinolysis factors of two currently used "sub-50" oral contraceptive preparations (OCs), one containing 750 micrograms lynestrenol and 37.5 micrograms ethinyl estradiol (LYN EE) and the other containing 150 micrograms levonorgestrel and 30 micrograms ethinyl estradiol (LNG-EE), in groups of about 25 women aged 21 +/- 2 years. After 3 months, plasminogen levels increased in the two experimental groups (LYN EE and LNG-EE), by 40% and 32%, respectively. This change was positively correlated with changes in ceruloplasmin levels, indicating that an estrogenic effect might be involved. Histidine-rich glycoprotein concentration decreased by 26% and 16%, respectively. Tissue-type plasminogen activator (t-PA) activity increased by 260% and 167%; t-PA antigen decreased by 12% and 18%, and t-PA inhibitor activity decreased by 31% and 32%, respectively. In the coagulation system, in both groups factor XII increased by 47% and 34%, respectively. The main inhibitor of factor XII, C1-inactivator, decreased slightly, but this was significant only in the LNG-EE group. The von Willebrand factor antigen fell by 8% and 9%, whereas factor VIII activity did not change. Antithrombin III antigen decreased by 14% in both groups. Factor IX activity increased by 15% and 21%. The difference in hormonal effects of both preparations was reflected by the increases in sex hormone binding globulin (by 130% and 21%) and ceruloplasmin (by 98% and 51%), indicating that LYN-EE had a more estrogenic potency than LNG-EE. In a control group of 25 matched subjects, who were observed simultaneously, we found no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108430 TI - In vitro correlation of platelet aggregation with occurrence of disseminated intravascular coagulation and subacute bacterial endocarditis. AB - Platelet-bacterial interactions were examined in vitro by incubating organisms isolated from patients with septicemia with normal platelet-rich plasma. The potency of various species of gram-positive and gram-negative bacteria to induce irreversible platelet aggregation was then determined in an aggregometer. The aggregation curves produced by the bacteria resembled the normal platelet response to collagen and were impeded by the presence of aspirin. Strains of Staphylococcus aureus and Pseudomonas aeruginosa isolated from 25 different patients produced maximum increases in light transmission and irreversible platelet aggregation with relatively rapid mean aggregation times; six of these patients had clinical and laboratory evidence of disseminated intravascular coagulation. In contrast, isolates of alpha streptococcus and Staphylococcus epidermidis induced irreversible platelet aggregation much less commonly and were associated with considerably longer mean aggregation times. None of the latter group of patients had evidence of disseminated intravascular coagulation. Isolates of bacteria from a small number of patients with subacute bacterial endocarditis uniformly induced irreversible platelet aggregation. Addition of paired bacterial isolates to normal platelet-rich plasma demonstrated a synergistic aggregation response. These data suggest that a relative hierarchy exists in bacterial strain potency to induce irreversible platelet aggregation. The rapidity and degree of aggregation in vitro correlated well with the clinical and laboratory evidence for subacute bacterial endocarditis and disseminated intravascular coagulation in vivo. These observations may provide useful adjunctive laboratory information to help establish the diagnosis of subacute bacterial endocarditis, especially in the clinical setting where the classical findings of endocarditis are not obvious during initial presentation. PMID- 3108431 TI - Evaluation of fibrinolytic capacity by a combined assay system for tissue-type plasminogen activator antigen and function using monoclonal anti-tissue-type plasminogen activator antibodies. AB - An assay system has been developed that allows consecutive quantification of tissue-type plasminogen activator (t-PA) activity and t-PA antigen in the same plasma sample. In the first step t-PA is bound to an immobilized IgM monoclonal anti-t-PA antibody and functional activity of bound t-PA is quantified by its plasminogen-activating activity. In the second step the amount of bound t-PA antigen is determined by using a different peroxidase-labeled monoclonal anti-t PA antibody. In this combined assay system t-PA functional activity was found to depend not only on the amount of t-PA antigen but also on the amount of plasminogen activator inhibitor (PAI), whereas in the t-PA antigen assay PAI did not affect the results. In plasma samples obtained from normal controls t-PA activity was detected only in post-venous occlusion plasma (3.7 +/- 2.5 IU/ml), whereas 2.7 +/- 0.5 ng/ml t-PA antigen was found before and 12.6 +/- 4.4 ng/ml after venous occlusion. Using this combined assay system to study plasma samples from patients who did not respond to venous occlusion with shortening of the euglobulin clot lysis time (ECLT), it was possible not only to confirm that in none of these patients could t-PA activity be detected in the postocclusion plasma samples but also to subdivide that group of patients into a group of about 39% not reacting with normal t-PA antigen release to venous occlusion and into a second group of about 61% that reacted with normal t-PA antigen release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108432 TI - A case of nasal glioma and neurofibromatosis. A new association. AB - A man of 25 with von Recklinghausen's neurofibromatosis (VR) developed nasal polyps. Subarachnoid haemorrhage occurred shortly after surgical excision and he died 9 weeks later. Post-mortem examination showed chronic hydrocephalus due to aqueduct stenosis. Histologically the polyps were a nasal glioma, a forme fruste of anterior encephalocoele not previously associated with VR, though other cranial defects are well recognized. Nasal glioma should be considered in the differential diagnosis of nasal lesions in VR. PMID- 3108433 TI - Ossified segments of the stylohyoid ligament. A case of radiological misdiagnosis. AB - An ossified segment of the stylohyoid ligament was misdiagnosed as a foreign body. PMID- 3108434 TI - Intestinal apolipoprotein A-I and B-48 metabolism: effects of sustained alterations in dietary triglyceride and mucosal cholesterol flux. AB - In recent studies (1985. J. Lipid Res. 26:368-379 and 1986. J. Lipid Res. 27:30 39) we characterized aspects of synthesis of rat intestinal apolipoproteins (apo) A-I and B-48 in vivo, and their short term regulation by dietary and biliary lipid flux. We now report studies extending these observations to the effects on intestinal apoA-I and apoB-48 metabolism of sustained (3 or 6 weeks) isocaloric intake of diets containing 0-30% (by weight) triglyceride, the latter as either butter fat (saturated) or corn oil (polyunsaturated). Additional studies were conducted to determine, separately, the effects of perturbations of intestinal mucosal cholesterol flux and hypothyroidism on intestinal apoA-I and apoB-48 metabolism. Intestinal synthesis (% total protein) of apoA-I and apoB-48 was not influenced by either dietary triglyceride quantity or quality (saturated vs. polyunsaturated fat); the values that were obtained were strictly comparable to those of both chow-fed animals and animals maintained for 3 weeks on fat-free chow. Intestinal apoA-I synthesis was not influenced by either acute or chronic perturbations of mucosal cholesterol flux. Hypothyroid rats demonstrated a 50% suppression of jejunal apoA-I synthesis. Intestinal synthesis of apoB-48, by contrast, appeared to undergo regulation by chronic (but not acute) perturbations of mucosal cholesterol flux. Maneuvers that augmented intestinal cholesterol uptake (particularly hypothyroidism) appeared to suppress intestinal apoB-48 synthesis by over 40%, while Surfomer (AOMA) administration reduced cholesterol absorption (control, 54 +/- 7%; AOMA, 26 +/- 8%; P less than 0.0005) and resulted in a 24% increase in apoB-48 synthesis by jejunal enterocytes. Intracellular intestinal lipoproteins demonstrated marked cholesteryl ester enrichment of the triglyceriderich lipoprotein fractions in hypercholesterolemic, hypothyroid rats. When all the groups were compared, cholesterol absorption (used as an index of mucosal cholesterol uptake) was negatively correlated with jejunal apoB-48 synthesis (r = -0.92, P less than 0.05). The data suggest that regulation of rat intestinal apoA-I and apoB-48 metabolism is independent of triglyceride flux. It is further concluded that an important regulatory effect of mucosal cholesterol flux can be demonstrated on enterocyte apoB-48 synthesis. Finally, the data suggest the additional possibility that circulating levels of thyroid hormone may exert an independent effect on the expression of rat intestinal apolipoproteins A I and B-48. PMID- 3108435 TI - Iodinated proteins in normal human thyroid gland. Thyroid albumin. AB - Iodinated proteins in normal thyroid tissue extracts were analyzed immunochemically, immunohistochemically and physicochemically after isoelectric focusing. An albumin-like protein ranging from pI 4.80 to 5.21 was found in normal human thyroid tissue extracts, and its pI range was not compatible with that of serum albumin ranging from pI 4.85 to 6.16. An immunodiffusion study suggests that T3 loosely combines with the albumin-like protein, and that this compound is so-called thyroid albumin. Amino acid analysis revealed a difference in the basic amino acid composition of thyroid albumin and serum albumin, and our immunohistochemical study showed that thyroid albumin and T3 were localized in follicular epithelial cells, but not in the colloid. Based on these results, thyroid albumin may be described as consisting of T3 and an albumin-like protein which is distinguishable from serum albumin and distinct from thyroglobulin immunochemically. It appears that a low molecular weight hormone like T3 can be detected when it combines with a protein molecule. Recently, DeGroot et al. (1975) suggested a collateral pathway of hormone metabolism through the thyroid albumin in thyroid follicular cells. Our results seem to support the existence of this pathway. PMID- 3108436 TI - Cost-benefit analysis of diagnosis and treatment of syphilis in pregnant women. PMID- 3108437 TI - Inhibin-like activity in Sertoli cell culture media and testicular homogenates from rats of various ages. AB - The influence of age on testicular inhibin in untreated, neonatally hemicastrated and prenatally irradiated rats was studied using in-vivo and in-vitro experiments. In testicular cytosols prepared from 1-, 7-, 14-, 21-, 42- and 63 day-old rats concentrations of testicular inhibin could be measured with an in vitro bioassay method using dispersed pituitary cells. Preparations of testicular cytosols caused a dose-dependent suppression of pituitary FSH secretion, whereas no effects were found on LH secretion. Testicular content of inhibin increased gradually with age, while after 14 days of age a relatively large increase of peripheral FSH concentrations occurred in all experimental groups. Neonatal hemicastration or prenatal irradiation resulted in decreased inhibin content of the testis and increased plasma FSH levels. The production of inhibin activity by Sertoli cells obtained from 7-, 14-, 21-, 42- and 63-day-old normal rats was measured during a 24-h incubation period on the third day of culture. The inhibin production per 10(6) plated Sertoli cells decreased rapidly after 14 days of age and the lowest production of inhibin was found in Sertoli cells from rats of 63 days of age. After pre-incubation with ovine FSH significantly larger amounts of inhibin activity were detected in spent media from 21-day-old rat testes. In contrast, suppression of inhibin production was found after pre-culture in the presence of testosterone at most of the ages studied. These data from in-vivo and in-vitro experiments indicate that a reciprocal relationship exists between pituitary FSH secretion and inhibin production before the age of 21 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108438 TI - Effects of catecholaminergic blockade by haloperidol or propranolol at different stages of the oestrous cycle on ovulation and gonadotrophin levels in the rat. AB - Rats with a 4-day oestrous cycle were injected with 2.5 mg haloperidol/kg, a dopaminergic blocker, or with 2.0 mg propranolol/kg, a beta 1- and beta 2 receptor blocker, at 13.00 h on oestrus, dioestrous day 1, dioestrous day 2 or pro-oestrus. Animals were autopsied on the next expected day of oestrus. Haloperidol blocked ovulation when injected on oestrus, dioestrous day 1 or pro oestrus and was less effective when injected on dioestrous day 2. Propranolol caused a decrease in the number of ova shed when injected on dioestrous day 2 or pro-oestrus. Serum concentrations of FSH at oestrus were below the control values in those animals in which ovulation was blocked by haloperidol. No significant changes in serum concentrations of LH were observed. The normal gonadotrophin peak which occurs during the afternoon of pro-oestrus was blocked by administration of haloperidol on oestrus or dioestrous day 1. Administration of gonadotrophin-releasing hormone (GnRH) to haloperidol-treated animals on oestrus or dioestrous day 1 did not restore ovulation or increase serum FSH levels. When the same dose of GnRH was given to rats treated with haloperidol on pro-oestrus, they all ovulated and their FSH levels rose normally. Treatment with both FSH and LH of rats given haloperidol at oestrus restored ovulation in 50% of the animals, whereas it was ineffective in animals treated on dioestrous day 1. Fifty per cent of the animals treated with haloperidol on oestrus or dioestrous day 1 ovulated when oestradiol benzoate was injected on dioestrous day 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108439 TI - Endogenous testosterone enhances growth hormone (GH)-releasing factor-induced GH secretion in vitro. AB - The influence of endogenous gonadal steroids in male and female rats on basal and growth hormone-releasing factor (GRF)-stimulated GH secretion from perifused anterior pituitaries was studied. After 75 min of perifusion with basal medium, freshly dissected pituitaries were exposed to human GRF(1-44) (10 nmol/l) for 15 min. Neonatal (day 1-2) or prepubertal (day 25) gonadectomy of male rats suppressed baseline GH release (ng/min per mg dry weight) as well as GRF stimulated GH release by 40-70%. This effect was slightly more pronounced in neonatally gonadectomized animals. In prepubertally gonadectomized male rats, the suppression of GH release was completely reversed by testosterone replacement therapy. In female rats, prepubertal gonadectomy did not affect GH secretion from perfused pituitaries. However, treatment of ovariectomized female rats with oestradiol reduced baseline and GRF-induced GH release to levels lower than those observed in sham-operated or vehicle-treated ovariectomized animals. The data suggest that testicular androgen secretion in adult male rats increases the pituitary GH release in response to GRF in vitro, whereas ovarian oestrogen secretion is of less importance for the GRF responsiveness of female rat pituitaries. PMID- 3108440 TI - Specific binding sites for LH/chorionic gonadotrophin, low-density lipoprotein, prolactin and FSH in homogenates of human corpus luteum. I: Validation of methods. AB - The specific binding of 125I-labelled human chorionic gonadotrophin (hCG), human low-density lipoprotein (hLDL), human FSH (hFSH) and human prolactin (hPRL) to homogenates of human corpus luteum tissue was measured. Specific binding of 125I labelled hCG was dependent on the temperature and duration of incubation, was inhibited by divalent metal ions or chelating agents, and increased linearly with homogenate concentration. Recovery of bound hormone was more effective using Millipore filtration or polyethylene glycol precipitation compared with centrifugation alone. Binding of 125I-labelled hCG was inhibited specifically by low levels of hCG and human LH (hLH) but not by ovine LH or bovine LH. Incubation of human luteal tissue with ice-cold citrate buffer (pH 3) released more than 90% of specifically bound 125I-labelled hCG within 5 min. This treatment inactivated LH receptors, but did not affect the immunoactivity of hLH released, enabling the measurement of released hormone by radioimmunoassay. Scatchard plots of binding of 125I-labelled LDL to human corpus luteum demonstrated a single class of binding sites. Binding was saturable, increased linearly with increasing concentration of homogenate, and was displaceable by low concentrations of unlabelled LDL. Binding of 125I-labelled hPRL to human luteal homogenates was increased by Mg2+ and was specific for lactogenic hormones (human prolactin, human growth hormone and ovine prolactin). Binding of 125I-labelled hFSH was not dependent on divalent metal ion concentration (in marked contrast to hFSH binding to immature pig granulosa cell receptors) and was displaced by hFSH preparations but not by hPRL, ovine LH or hCG at 1 microgram/ml. These results establish optimal conditions and hormone specificities for the measurement of human luteal gonadotrophin and LDL receptors, and methods for the estimation of hLH/hCG endogenously bound to human corpus luteum tissue. PMID- 3108442 TI - Thermal dependence of maximum Ca2+-activated force in skinned muscle fibres of the toad Bufo marinus acclimated at different temperatures. AB - Mechanically skinned muscle fibres from the twitch region of the iliofibularis muscle of cool- (16 +/- 1 degree C) and warm- (32 +/- 1 degree C) acclimated cane toads (Bufo marinus) were activated maximally by Ca2+ in solutions of different pH and at different temperatures (approx. 1-35 degrees C). Acclimation of up to 12 weeks at 16 degrees C and up to 8 weeks at 32 degrees C did not modify the marked thermal dependence of isometric force in the skeletal muscle fibres of the cane toad. The prominent decline of maximum Ca2+-activated force at lower temperatures, a property which is not characteristic of muscles from other anurans, was associated with an obvious decline in fibre stiffness at temperatures below about 20 degrees C, regardless of the temperatures at which the toads were kept prior to experimentation. The results suggest that the decline of isometric force at lower temperatures is due both to a reduction in the number of cross-bridges and to a decrease in the force output per cross bridge. The maximum Ca2+-activated force response increased when fibres were activated in solutions of increasing pH at all temperatures investigated. This trend is expected to have a compensatory effect on the thermal dependence of the maximum Ca2+-activated force under physiological conditions, because of the elevation of intracellular pH as temperature declines. The isometric force did not depend on the concentration of the zwitterionic species of the pH buffer in solutions. The skinned fibre preparation developed a Ca2+-insensitive residual force following maximal activation. The increment in residual force followed a linear relationship with the duration of activation at a given temperature and a power relationship of activation temperature for a given duration of activation. Fibres from warm-acclimated animals developed less residual force following activations at 15 degrees C than did fibres from cool-acclimated animals, suggesting that thermal acclimation may substantially reduce the magnitude of this phenomenon at temperatures below 20 degrees C. PMID- 3108441 TI - Extracellular accumulation of proline, serine and trehalose in the haemolymph of osmoconforming brackish-water mosquitoes. AB - Larvae of Culex tarsalis, a mosquito, are capable of surviving and developing in dilutions of sea water ranging from 0 mosmol l-1 to 700 mosmol l-1. In waters more dilute than 400 mosmol l-1, the larvae osmoregulate, whereas in those more concentrated than 400 mosmol l-1, the osmotic strength of the haemolymph parallels that of the medium, i.e. the larvae osmoconform. Over the full range of external concentrations tested, the larvae regulate the levels of Na+, K+, Mg2+, Ca2+ and Cl- in the haemolymph. Analyses of haemolymph samples from larvae adapted to media of 50 mosmol l-1 or 600 mosmol l-1 indicate that the increase in haemolymph osmotic concentration observed in media above 400 mosmol l-1 is due to the accumulation of organic compounds, particularly proline, serine and trehalose. PMID- 3108443 TI - Development of fetal thymocytes in organ cultures. Effect of interleukin 2. AB - Most fetal thymocytes from 14-d mouse embryos are Thy-1+, L3T4-, Ly-2-, and express the receptor for interleukin 2 (IL-2). The development of thymocytes has been followed in fetal thymus organ cultures. When fetal thymus from 14-d embryos were cultured for a 6-d period, thymocytes increased in number 20-40-fold, and 95% became Thy-1+, L3T4+, Ly-2+. The addition of IL-2 to organ cultures of 14-d fetal thymus inhibited, in a dose-dependent manner, cell proliferation and the appearance of Thy-1+, L3T4+, Ly-2+ thymocytes. The addition of IL-2 also resulted in the appearance of a population of cells that were cytotoxic for syngeneic and allogeneic fetal thymocytes and syngeneic tumour targets. While the events that lead to the expression of the IL-2 receptor on 14-d fetal thymocytes are unknown, IL-2 in fetal thymus organ cultures inhibits the normal maturation of fetal thymocytes and raises the question of whether the cytotoxic cells that appear reflect selection through an alternative pathway of development. PMID- 3108445 TI - Phenotypic analysis of the inflammatory exudate in murine lymphocytic choriomeningitis. AB - The massive inflammation of the cerebrospinal fluid (CSF) which occurs in adult mice injected with lymphocytic choriomeningitis virus (LCMV) has been analyzed by flow microfluorometry (FMF). The great majority of the T cells detected by direct examination of freshly obtained CSF were found to be Lyt-2+, with an almost total absence of L3T4+ lymphocytes. The Lyt-2/L3T4 ratio of lymphocytes in blood was within normal limits. Predominance of the Lyt-2+ subset was confirmed by culturing the CSF cells after mitogenic stimulation. In addition, the T lymphocytes in CSF of cyclophosphamide-suppressed, virus-infected recipients that had been injected 4 d previously with LCMV-immune spleen cells were almost entirely donor Lyt-2+ cells, while the nonlymphoid elements were exclusively of host origin. However this pattern of donor and host T cell distribution was reversed when the LCMV-infected recipients were not immunosuppressed. The frequency of LCMV-specific CTL precursors in CSF taken immediately before the development of symptoms was as low as 1:3,000 cells. Thus most of the T lymphocytes extravasating into the CSF of mice with LCM are passive participants recruited as a consequence of the function of relatively few LCMV-specific effector T cells. The dominance of the Lyt-2+ T cell subset in the CSF of mice with LCM is intriguing. PMID- 3108444 TI - Chemoattractant-induced activation of c-fos gene expression in human monocytes. AB - Human monocytes use the products of phosphoinositide hydrolysis (1,2 diacylglycerol and inositol 1,4,5-triphosphate) as second messengers to trigger rapid cellular activation during the occupancy of chemoattractant receptors. The effect of chemoattractants on modulation of gene expression in monocytes was examined in this study. The chemoattractants FMLP and platelet-activating factor induced the progressive increase of c-fos RNA to 6-15-fold over those of control within 30 min after treatment. Similar kinetics of c-fos gene activation was also observed when cells were treated with PMA or sn-1,2-dioctanoylglycerol, but not with the calcium mobilizer ionomycin, suggesting a role for protein kinase C in gene regulation by chemoattractant receptors. Activation of c-fos gene expression by FMLP is mediated through a pertussis toxin-sensitive G protein, since pertussis toxin treatment of the cells blocked the induction of the c-fos gene by FMLP but not PMA. The level of c-myc RNA was slightly decreased after 1 h of treatment with chemoattractants, but not with PMA or diacylglycerol. This implies that chemoattractant receptor occupancy generates signals beyond protein kinase C activation that are capable of selectively downregulating monocyte gene expression. The effect of FMLP and PMA on the accumulation of c-fos RNA appears to result from altering both the rate of transcription and message stability. These observations indicate that signals generated through chemoattractant receptor occupancy may regulate monocyte function at the genetic level. PMID- 3108446 TI - Variable capacity of L3T4+ T cells to cause lethal graft-versus-host disease across minor histocompatibility barriers in mice. AB - Highly purified populations of L3T4+ and Lyt-2+ T cell subsets were compared for their capacity to cause lethal GVHD in six different H-2-compatible, multiple minor histocompatibility antigen-different murine strain combinations. In four of these combinations (C3H.SW----B6, DBA/2----B10.D2, B10.BR----CBA, and B10.S--- SJL), lethal GVHD appeared to be caused almost entirely by Lyt-2+ cells; the injection of L3T4+ cells resulted in low mortality even when these cells were presensitized to the recipient antigens. In the remaining two combinations (B10.D2----DBA/2 and B10.D2----BALB/c), L3T4+ T cells were able to cause a high incidence of GVHD and were more potent than the Lyt-2+ cells. The implications of these findings are discussed. PMID- 3108447 TI - Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. AB - We present evidence that human peripheral blood lymphocytes, free of contaminating monocytes, rapidly produce high levels of tumor necrosis factor (TNF) when stimulated with phorbol diester and calcium ionophore, and lower but significant levels of TNF when stimulated with mitogens. These two types of inducers act preferentially on T cells, both CD4+ and CD8+. NK cells produce TNF only when stimulated with phorbol diester and calcium ionophore, and they do so at a much lower level than T cells. The procedures used in the purification of lymphocytes and the differential ability to respond to various inducers allow us to exclude that monocytes or basophils contaminating the lymphocyte preparation participate in the production of TNF. In particular, LPS, a potent inducer of TNF production from monocytes, is unable to induce significant levels of TNF in the lymphocyte preparations. The TNF produced by lymphocytes has antigenic, physicochemical, and biochemical characteristics identical to those of the TNF produced by myeloid cell lines or monocytes upon stimulation with LPS. LT is also produced by lymphocyte preparations. Production of TNF and LT proteins in response to the different inducers is paralleled by accumulation of cytoplasmic TNF and LT mRNA. Both at mRNA and at protein levels, stimulation of T lymphocytes with phorbol diester and calcium ionophore preferentially induces TNF, whereas mitogen stimulation preferentially induces LT. Our data suggest that the TNF and LT genes, two closely linked genes encoding two partially homologous proteins with almost identical biological functions, are independently regulated in lymphocytes. PMID- 3108448 TI - Differentiation-linked secretion of urokinase and tissue plasminogen activator by normal human hemopoietic cells. AB - Previous studies have shown that the response of patients with acute myeloid leukemia to induction chemotherapy can be predicted by the species of plasminogen activator that their cells secrete. Patients whose cells secreted tissue plasminogen activator (tPA) only failed to respond to combination chemotherapy. Individuals whose leukemic cells display features of the early progenitor phenotype also respond poorly to therapy. This suggested that the two species of plasminogen activator secreted by leukemic cells might be produced by normal cells at distinct stages of differentiation. These results indicate that the secretion of the two enzyme types is a differentiation-linked property of normal cells with tPA being produced by granulocyte/macrophage progenitors and urokinase by more differentiated cells and by mature neutrophils and macrophages. PMID- 3108450 TI - Some highlights of animal virus research in 1986. PMID- 3108449 TI - Production of a T cell hybridoma that expresses the T cell receptor gamma/delta heterodimer. AB - We have produced a T cell hybridoma line by fusion of an IL-2-dependent, long term T cell receptor (TCR) gamma/delta+ Thy-1+, bone marrow-derived, dendritic epidermal cell line to the BW5147 tumor line. The resultant hybridoma was rapidly growing, lymphokine independent, and expressed T3 in association with the TCR gamma/delta heterodimer. Several subclones of the hybridoma line produced easily detectable levels of IL-2 after stimulation by anti-T3 or Con A. The availability of these cloned cell lines should greatly facilitate further functional, biochemical, and molecular studies of the TCR delta chain. PMID- 3108451 TI - Human immunodeficiency virus (HIV) infection in the regular sexual partners of homosexual men with AIDS and persistent generalised lymphadenopathy. AB - Thirty-five homosexual men who had been the regular sexual partners (for at least 6 months) of anti-HIV-positive patients with AIDS (N = 18) or PGL (N = 17) were studied. Twenty-one (60%) were seropositive, but 14 (40%) were consistently anti HIV-negative. The duration of relationship with the index case was not statistically different in seropositive compared to seronegative partners; median 26 months (range 7-60) vs 30 months (range 7-60). However, seropositive partners had a significantly higher monthly number of other sexual partners and sexually transmitted diseases and a higher frequency of insertive and receptive anal intercourse in the preceding five years. The risk of acquiring HIV infection was significantly increased by frequent receptive anal intercourse when the frequency of insertive was controlled for but not the converse. Seronegative partners had undetectable antibodies by live and fixed cell immunofluorescence and by radioimmunoprecipitation and were repeatedly negative by competitive enzyme immunoassay. Furthermore, the sera of seronegative partners lacked HIV neutralising activity. Peripheral blood mononuclear cells (PBMCs) from seronegative partners, stained with monoclonal antibodies to seven different CD4 epitopes, revealed no differences when compared to those from heterosexual controls and no qualitative differences from cells from seropositive individuals. In addition, PBMCs from seronegative partners could be productively infected by HIV in vitro. If resistance to infection in seronegative partners exists, then it is likely that mechanisms other than a specific humoral immunity or CD4 polymorphisms are involved. PMID- 3108452 TI - Overview of the present state of MAO inhibitors. AB - In this paper an overview of the present state of monoamine oxidase inhibitors (MAOIs) is presented. The irreversible inhibitors are firstly considered. They have been divided into four chemical types: substituted hydrazine, cyclopropylamine, propargylamine and allylamine derivatives. Moreover, a tetrahydropyridine derivative (MPTP), recently described as an irreversible inhibitor of MAO-B, has been included among the irreversible MAOIs. The reversible inhibitors such as tetrahydro-beta-carbolines and salsolinol, phenylalkylamines: amphetamine, amiflamine and 2,3-dichloro-alpha-methyl benzylamine. Among the short acting or reversible inhibitors the 4-(2 benzofuranyl) piperidine series and the morpholinoethylamino derivatives are discussed. Finally the oxazolidinone series is presented separately, as in this series reversible or irreversible inhibitors of the A or B form of MAO have been obtained. PMID- 3108453 TI - Amine oxidases and their endogenous substrates (with special reference to monoamine oxidase and the brain). AB - The roles of MAO, BzO, DAO and PAO in the metabolism of endogenous substrates and the functional implications of their action and inhibition is reviewed, the emphasis being on MAO on one hand and on brain on the other. The major issues are the following: There is no discrete subdivision into substrates selective for MAO A, MAO-B, or mixed ones, but rather a continuum. Tissue differences in substrate specificity are not likely to be due to molecular variability of MAO. For the deamination of DA, 5-HT and PEA at least, the relative participation of either MAO form in a given tissue is primarily determined by the relative abundance of the two forms; only at 10(-5) M and above, substrate concentration begins to matter also. In vivo, compartmentation is of paramount importance: since there seems to be more MAO-A than B inside monoaminergic neurons, DA, 5-HT and NA are predominantly metabolized by MAO-A if metabolism occurs mainly intraneuronally. Conversely, since MAO-B is more abundant extraneuronally, e.g. in glia cells, the relative participation of this form increases if a significant portion of these amines is deaminated outside monoaminergic neurons. In vivo, monoamine deamination is reduced concomitantly with the degree of MAO inhibition, whereas signs of increased transmitter function are only observed if enzyme inhibition is at least 80%. This is likely to be the result of the action of compensatory mechanisms such as feedback inhibition of transmitter release and synthesis. BzO is particularly abundant in vascular tissue, lung and bone. Low levels are found in brain. Endogenous substrates and physiological function are not known. DAO also occurs only in minimal amount in brain, if at all. Its principal substrates are histamine and the polyamines, and the disposal of these amines is probably its main function. Of the PAO's, the type of enzyme found in the rat liver attacks the secondary amino groups and may have a more prominent role in the metabolism of polyamines in the brain than in the periphery. Bovine plasma PAO, which attacks primary amino groups, is only found in the serum of ruminants, but not other species. Its function in the metabolism of polyamines is not known. PMID- 3108454 TI - A reaction between captopril (a high blood pressure drug) and gold(I)-thiomalate. AB - A reaction of gold(I) thiomalates [Au(tm)], "Myocrisin" (an antiarthritic drug), with captopril (a high blood pressure drug) was carried out in aqueous solution at pH 7.20 using 13C NMR spectroscopy. Captopril, which exists in the cis (c) and trans (t) isomer forms, binds strongly with gold(I), ejecting thiomalate (Htm) as free ligand into solution. PMID- 3108455 TI - Effects of methylprednisolone and the combination of alpha-tocopherol and selenium on arachidonic acid metabolism and lipid peroxidation in traumatized spinal cord tissue. AB - Traumatic injury of the spinal cord leads to a series of pathological events that result in tissue necrosis and paralysis. Among the earliest biochemical reactions are hydrolysis of fatty acids from membrane phospholipids, production of biologically active eicosanoids, and peroxidation of lipids. This study examines the effect of agents purported to improve recovery following spinal cord trauma, methylprednisolone sodium succinate (MPSS) and the combination of alpha tocopherol and selenium (Se), on the posttraumatic alterations of membrane lipid metabolism. Pretreatment with either MPSS or alpha-tocopherol and Se reduced the trauma-induced release of total FFA including arachidonate in the injured spinal cord tissue. In addition, these agents decreased the postinjury levels of prostanoids. Pretreatment with either MPSS or alpha-tocopherol and Se also completely prevented the trauma-induced loss of cholesterol while inhibiting the increase of a cholesterol peroxidation product, 25-hydroxycholesterol. These data suggest that: perturbation of membrane lipid metabolism may contribute to the tissue necrosis and functional deficit of spinal cord injury and MPSS or the combination of alpha-tocopherol and Se may protect injured spinal cord tissue, at least in part, by limiting these posttraumatic membrane lipid changes. PMID- 3108457 TI - Apnoea testing to confirm brain death in clinical practice. PMID- 3108456 TI - Protein turnover in acid maltase deficiency before and after treatment with a high protein diet. AB - A patient with acid maltase deficiency was treated with a high protein diet for 7 months. Protein turnover expressed in terms of lean body mass was shown to be increased in this patient before the diet but was markedly reduced following the diet. The patient improved clinically whilst on the diet both subjectively and in terms of mobility, breathing and reduced peripheral cyanosis at rest. PMID- 3108458 TI - Thyrotropin-releasing hormone (TRH) in murine motor neuron disease (the wobbler mouse). AB - Clinical benefits of thyrotropin-releasing hormone (TRH) were tested in wobbler mice, an animal model of motor neuron disease. After the disease was clinically recognized at 3-4 weeks, the animals were divided into two groups, each group consisting of 5 pairs of wobbler mice and normal littermates. TRH (50 mg/kg) and normal saline (NS) were injected intraperitoneally daily, 6 times per week for 9 weeks, in a double-blind study. Weekly assessments consisted of front paw grip strength, push walking, body weight, and semiquantitative grading. At the end of the trial, the brain and spinal cord were sampled to measure TRH and cyclo (His Pro) concentrations. Progression of motor neuron disease was evident in wobbler mice, regardless of treatment. Descriptive semiquantitative gradings showed the tendency of improvement in TRH-treated wobbler mice. In saline-injected controls, TRH levels in the cervical spinal cord were significantly increased (P less than 0.01) in wobbler mice compared to littermates. However, with TRH treatment, there was no significant difference in TRH and cyclo (His-Pro) levels in any neural tissue between wobbler and controls. The lack of clinical benefits with TRH in wobbler mice may be due to increased TRH levels found in diseased spinal cord in murine motor neuron disease. PMID- 3108459 TI - Comparison between pial and intraparenchymal vascular responses to sympathetic stimulation under hypercapnic conditions. With special reference to the mechanism for escape phenomenon. AB - We have shown that secondary vasodilation ('escape' phenomenon) during sympathetic nerve stimulation occurs in the intraparenchymal vessels but not remarkable in the pial vessels. To test a possible role of CO2 accumulation in the brain tissue in this phenomenon, the responses of pial and intraparenchymal vessels to sympathetic nerve stimulation were investigated during hypercapnia in 9 cats by using a video camera photoelectric system. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min during hypercapnia (PaCO2 = 50 +/- 2 mm Hg). The intraparenchymal vessels as well as pial vessels remained constricted throughout the stimulation. Secondary dilation of the intraparenchymal vessels as seen at the later stage of sympathetic stimulation during normocapnia was not observed under the hypercapnic conditions. We assume that the arterial CO2 tension was so high that the constriction of inflow vessels could not result in accumulation of CO2 in the brain parenchyma. The accumulation of chemical metabolites as represented by CO2 is therefore considered to be the most probable mechanism underlying the escape phenomenon of the intraparenchymal vessels. PMID- 3108460 TI - Synergistic antiproliferative effect of recombinant alpha-interferons with recombinant gamma-interferon. AB - Two human tumor cell lines were studied for their response to the antiproliferative effect of recombinant human interferons (IFNs) alpha 2, alpha 4, a hybrid alpha (delta 4 alpha 2 Bgl II alpha 1), and gamma, individually and in combination. Natural human alpha-IFN was used as a reference point for all experiments. RT4 (bladder carcinoma) cells were overall more sensitive to the antiproliferative effects of the IFNs than A2182 (lung adenocarcinoma) cells. Three-way analysis of variance indicated that the relative effectiveness of the alpha-IFNs was alpha 2 less than alpha 4 less than hybrid alpha less than natural alpha-IFN. On an international reference unit per milliliter basis, gamma-IFN was 50- and 75-fold more effective than natural alpha-IFN and hybrid alpha-IFN in RT4 cells and 5.6-, 12.1-, and 14.9-fold more effective than alpha 4-, hybrid alpha-, and natural alpha-IFN in A2182 cells. In contrast, when recalculated on a nanogram per milliliter basis, gamma-IFN was only threefold more effective than the hybrid alpha-IFN in RT4 and approximately twofold less effective than alpha 4 and the hybrid alpha in A2182. Combinations of alpha-IFNs gave additive or antagonistic effects. When any of the alpha-IFNs were combined with the gamma IFN, however, a synergistic antiproliferative effect was seen. The magnitude of the synergy was dependent upon the concentration of gamma-IFN used and the type of alpha-IFN in the combination. Antagonistic effects were seen at the lowest gamma-IFN concentration studied (0.2 IRU/ml). Synergy also varied according to the potency of the alpha-IFN used. PMID- 3108461 TI - Resistance to biological and chemical challenge in rodents treated with xerosin II, a natural product of Achromobacter xerosis. AB - The biological response-modifying activity of acid-precipitable material from Achromobacter xerosis was first described as suppression of viral pneumonia in mice. Later, this acid-precipitable material (xerosin) was found to have antiinflammatory activity and to induce tumor regression in chickens infected with Rous sarcoma virus. Here, we report further purification of xerosin resulting in a product (xerosin II) that retains high biological activity against viral and endotoxin-induced pneumonia in mice. In addition, we describe new activities of xerosin II in two rat tumor systems. Female CD rats received gastric intubations of 7,12-dimethylbenz(a)anthracene; 2 weeks later, half began 4 weeks of treatment with xerosin II, while others received saline only. Xerosin II treatment significantly delayed the appearance of the first palpable mammary tumors per rat. In female F344 rats implanted with the 13762 mammary tumor, 4 weeks of xerosin II treatment prolonged the survival of rats by an average of 5 11 days (12-24%) in two separate trials. Tumor growth and incidence of metastasis appeared unaffected by xerosin II treatment. Thus, this refined bacterial extract proved to be a potent biological response modifier in four different rodent systems. PMID- 3108462 TI - Endogenous production of cytotoxic factor in mice induced by a combination of interferon-gamma and heterologous fibrinogen. AB - The ability of heterologous fibrinogen in combination with interferon (IFN)-gamma to induce endogenous production of cytotoxic factor was examined. Heterologous but not homologous fibrinogen induced high production of cytotoxic factor in IFN gamma-primed mice. The cytotoxic activity was maximal 1 h after this triggering. The LD50 value of heterologous fibrinogen in mice was greater than 250 mg/kg i.v. But heterologous fibrinogen induced antibody, causing anaphylaxis. Therefore, the effect of successive injections of fibrinogens from a different species was tested. Cytotoxic factor could be produced repeatedly by successive treatments with a combination of IFN-gamma and heterologous fibrinogen from one species for 1 week, although the cytotoxic activity induced by successive injections gradually decreased. After the decrease of the triggering effect of heterologous fibrinogen of one species, heterologous fibrinogen from a different species could induce cytotoxic activity at the same level as that after the first triggering. Thus, a combination of IFN-gamma and heterologous fibrinogen is effective for cytotoxic factor production, provided different heterologous fibrinogens are used successively. This combination should be useful for endogenous cytotoxic factor production in clinical trials. PMID- 3108464 TI - Continuous monitoring of alveolar and inspiratory concentrations of anesthetic and respiratory gases is safe, simple, and cost-effective. PMID- 3108463 TI - Immunocytochemical localization of UDP-galactose: ceramide galactosyltransferase in myelin and oligodendroglial cells of rat brain. AB - Specific antibodies were prepared against rat-brain UDP-galactose:ceramide galactosyltransferase (CGalT) and used to study the localization of this enzyme at light and electron microscopic levels. Using an immunocytochemical technique the presence of CGalT was revealed in the cytoplasm and processes of oligodendrocytes and in myelin sheaths of developing and adult rat brain. No immunostaining was detected in neurons or astrocytes. At the ultrastructural level the immunostaining of oligodendrocytes was most intense at the periphery of cytoplasm and probably included plasma membrane. Among the intracellular organelles of oligodendrocytes, specific labelling was occasionally seen in the stacks of Golgi apparatus membranes. In myelin sheaths anti-CGalT staining seems to be restricted to the outermost and innermost lamellae. The finding of CGalT in distant portions of oligodendrocyte processes and in loosely wrapped myelin membranes might indicate that myelin galactocerebrosides are synthesized in the proximity of the site of their incorporation into the newly formed myelin. PMID- 3108465 TI - End-tidal carbon dioxide as a measure of arterial carbon dioxide during intermittent mandatory ventilation. AB - To determine if end-tidal carbon dioxide tension (PETCO2) is a clinically reliable indicator of arterial carbon dioxide tension (PaCO2) under conditions of heterogeneous tidal volumes and ventilation-perfusion inequality, we examined the expiratory gases of 25 postcardiotomy patients being weaned from ventilator support with intermittent mandatory ventilation. Using a computerized system that automatically sampled airway flow, pressure, and expired carbon dioxide tension, we were able to distinguish spontaneous ventilatory efforts from mechanical ventilatory efforts. The PETCO2 values varied widely from breath to breath, and the arterial to end-tidal carbon dioxide tension gradient was appreciably altered during the course of several hours. About two-thirds of the time, the PETCO2 of spontaneous breaths was greater than that of ventilator breaths during the same 70-second sample period. The most accurate indicator of PaCO2 was the maximal PETCO2 value in each sample period, the correlation coefficient being 0.768 (P less than 0.001) and the arterial to end-tidal gradient being 4.24 +/- 4.42 mm Hg (P less than 0.01 compared with all other measures). When all values from an 8 minute period were averaged, stability was significantly improved without sacrificing accuracy. We conclude that monitoring the maximal PETCO2, independent of breathing pattern, provides a clinically useful indicator of PaCO2 in postcardiotomy patients receiving intermittent mandatory ventilation. PMID- 3108466 TI - Technetium-99m bis (aminoethanethiol) complexes with amine sidechains--potential brain perfusion imaging agents for SPECT. AB - In an effort to develop new clinically useful technetium-99m bis(aminoethanethiol) ([99mTc]BAT) complexes for the evaluation of regional cerebral perfusion, two new BAT ligands containing amines in the sidechain were synthesized and subsequently complexed with 99mTc to yield the target complexes: [99mTc]DEA and [99mTc]TMPDA. Each complex was obtained as mixtures of two isomers, syn and anti, which were separated chromatographically. In biodistribution studies, both isomers of [99mTc]TMPDA showed little uptake in the brain. In contrast, the brain uptake values at 2 and 15 min for [99mTc]DEA-anti were 0.99 and 0.26, whereas, the corresponding values for DEA-syn were 2.27, 0.64% dose/organ, respectively. Autoradiographic studies (in rats) using both isomers of [99mTc]DEA show a fixed regional distribution and a higher concentration of radioactivity in the gray matter relative to the white matter. Planar imaging using [99mTc]DEA-syn clearly demonstrates localization of the complex in the brain with a T 1/2 of 41 min, suggesting some potential for use with single photon emission computed tomography. PMID- 3108467 TI - Comparison of several indium-111 ligands in labeling blood cells: effect of diethylpyrocarbonate and CO2. AB - The effect of oxine sulfate, oxine sulfonate, tropolone, and Merc (2 mercaptopyridine-1-oxide) were compared with oxine, with respect to their capability of labeling blood cells when complexed to indium-111 (111In). Indium 111 oxine sulfate performed similarly to [111In]oxine with regard to cell labeling capability. Indium-111 oxine sulfonate had no labeling ability. Indium 111 tropolone and Merc were not superior to [111In]oxine as cell labeling agents. Carbon dioxide (CO2) and a CO2 generating compound, diethyl pyrocarbonate, dramatically improved the cell labeling ability in plasma of [111In]tropolone and Merc. In the case of oxine, this improvement was less distinct. Theoretical aspects of the CO2 cell labeling stimulating effect are discussed in terms of intra- and extracellular transferrin and lactoferrin iron (indium) binding capacity. Indium-111 tropolone behaved favorably with respect to inhibition of leukocyte migration, compared with oxine and Merc. Combined with the property of easy cell labeling and good solubility in water, also in the complexed state, tropolone must be regarded as the most suitable cell labeling ligand. PMID- 3108468 TI - Time course of changes in rat serum apolipoproteins during the consumption of different low protein diets followed by a balanced diet. AB - The effects of protein malnutrition (PM) followed by refeeding a balanced diet on apolipoprotein and lipid contents of the serum lipoproteins were studied in young Wistar male rats. The changes of serum apolipoproteins were compared with the appearance of fatty liver during PM and its disappearance during refeeding. The control group (T) was fed a balanced diet containing 15% casein for 42 d. Two depleted groups (C) and (G1) were fed for 28 d low protein diets containing 2% casein and 5% gluten, respectively, and then were fed the balanced diet for 14 d. During PM a concentration of triacylglycerols (TGs) in liver in the two depleted groups increased; the level in rats fed 2% casein was twice that in rats fed 5% gluten. There was a significant negative correlation between serum TGs and liver TGs. The serum apolipoproteins (apo) did not respond consistently. The high density lipoproteins apo A-I, A-II and A-IV, which are more than 50% synthetized in the intestine, remained essentially unchanged, thus showing resistance to protein malnutrition. The very low density lipoproteins apo B and total apo C, which mainly originate from liver, were significantly lower in malnourished groups than in controls, while the liver TGs accumulated in malnourished groups. Only the levels of total apo C and apo B48 were correlated with hepatic TG steatosis during malnutrition and refeeding. PMID- 3108469 TI - Protein malnutrition and the function and fluidity of the intestinal microvillus membrane in growing rats. AB - The effect of protein malnutrition on the function, fluidity and composition of the intestinal microvillus membrane was studied in growing rats. Weanling male rats were fed diets containing 10% protein derived from either wheat gluten (experimental diet) or casein (control diet). Intestinal microvillus membranes were isolated after a 7-wk feeding period. The functionality of the membranes, as assessed by the level of activity of the four enzymes alkaline phosphatase, gamma glutamyl transpeptidase, leucine aminopeptidase and maltase, showed no difference between the membranes derived from the experimental and the control animals. Similar Arrhenius plot patterns of alkaline phosphatase activity (13-50 degrees C) and of the fluorescence anisotropy parameter (8-40 degrees C) were observed for both types of membranes with respect to the transition temperatures and energies of activation. In addition, the similarity between the membranes derived from the experimental and the control animals was also manifested in the cholesterol and phospholipid content. The study demonstrates that despite the extreme nutritional stress exerted on the gluten-fed rats, the integrity and functionality of the intestinal microvillus membrane was adequately maintained. PMID- 3108470 TI - The effect of vitamin C nutriture on complement component C1q concentrations in guinea pig plasma. AB - This study shows that guinea pigs fed 100 times the amount of vitamin C needed for growth and for prevention of scurvy have elevated levels of complement component C1q. C1q is a plasma protein rich in hydroxyproline, an amino acid whose biosynthesis requires ascorbate. C1q is essential for host defense against pathogens, both as a component of the classical complement pathway and as an opsonin in the phagocytosis process. We measured C1q in vitamin C-depleted guinea pigs that had been repleted for 4 wks with the following daily doses of ascorbate (mg/100 g body wt): 0.50 (suboptimal), 2.0 (adequate), 10 (ample) and 50 (tissue saturating). We measured C1q in three ways: indirectly by quantifying protein bound hydroxyproline and directly by hemolytic assay and by immunodiffusion against anti-C1q. Regardless of the method, plasma C1q was 30-50% higher in animals fed tissue-saturating ascorbate than in those fed adequate or suboptimal amounts of the vitamin (p less than 0.05, one-way analysis of variance, least significant difference test). These data confirm and significantly extend earlier work that provided indirect evidence for a relationship between C1q and ascorbate nutriture in the guinea pig. They are consistent with a possible relationship between ascorbate nutriture and host defense. PMID- 3108471 TI - Stability and specificity of rice bran trypsin inhibitor. AB - The stability and inhibitory specificity of rice bran trypsin inhibitor (RBTI) was investigated in an attempt to understand its nutritional significance. RBTI retained about 100% of its original activity over a pH range from 4 to 10 during 24-h incubation at 37 degrees C. In heat treatment, RBTI at acidic and neutral pH values still possessed about 50% of its initial activity after 30-min incubation at 100 degrees C, although it was completely inactivated during 15-min incubation at pH 10 and 100 degrees C. The effects of metal ions and some reagents on RBTI were examined and it was found that Hg ion reduced RBTI's inhibitory activity: The inhibitor lost 30-100% of its original activity upon incubation with a reducing, an oxidizing or a thiol reagent. Digestion tests on RBTI indicated that alpha-chymotrypsin did not affect the inhibitory activity and pepsin caused only a 30% loss of the initial inhibitory activity after 24-h digestion. To determine inhibitory specificity, bovine, hog, rat, and human trypsins were used as target enzymes bound to an immobilized RBTI column. Titrations of the purified enzymes with RBTI showed that bovine, hog, and rat trypsins were powerfully inhibited by the inhibitor, while human trypsin was only weakly inhibited. PMID- 3108472 TI - Effects of glucose and amino acid depletions on protein synthetic parameters in liver and skeletal muscle of rats during parenteral nutrition. AB - Rats were nourished by intravenous infusion of four different experimental solutions: total parenteral nutrition (TPN) solution (group I); glucose-depleted TPN solution (group II); amino acid-depleted TPN solution (group III); and glucose- and amino acid-depleted TPN solution (group IV). All except group I animals lost body weight and showed negative nitrogen balance during a 7-day experimental period; glucose-depleted groups II and IV generally suffered more severely than amino acid-depleted group III. However, the concentration of plasma albumin in group III was significantly lower than that in the other groups. The weights of liver and gastrocnemius muscles after 7 days of infusion with different nutrient compositions were fairly well correlated with the RNA/DNA ratios in these tissues. Infusion of nutritionally deficient solutions caused progressive disaggregation of polysomes in both liver and gastrocnemius muscles, indicating variable degrees of impairment of protein synthesis in these tissues. The changes in polysomal profiles were rapid and sensitive; the polysomal disaggregation was evident within one day of infusion with deficient solutions. The determination of polysomal profiles in various tissues may be useful in optimizing the composition of TPN solutions. PMID- 3108474 TI - Regression of experimental hamster cancer by beta carotene and algae extracts. AB - The effect of algae extract on tumor regression was studied. Phycotene (extract of Spirulina and Dunaliella algae) 250 micrograms in 0.1 ml MEM (minimum essential medium) was injected locally into DMBA (7, 12 dimethylbenz(a)anthracene)-induced squamous cell carcinomas of hamster buccal pouch in 20 animals. DMBA-induced carcinomas in 20 hamsters were injected locally with beta carotene 250 micrograms in 0.1 ml MEM; DMBA-induced carcinomas in 20 animals were injected locally with canthaxanthin, 250 micrograms in 0.1 ml MEM, and DMBA-induced carcinomas in 20 animals were injected locally with 13-cis retinoic acid, 250 micrograms in 0.1 ml MEM. Twenty animals with DMBA-induced carcinomas were sham-injected controls using 0.1 ml MEM. The various agents were injected into the tumor bearing right buccal pouches twice-weekly for four weeks. Total tumor regression was found in 30% of phycotene animals, 20% of beta carotene animals and 15% of canthaxanthin animals after four weeks. Partial tumor regression was found in the remaining 70% of phycotene animals, 80% of beta carotene animals and 85% of canthaxanthin animals. None of the 13-cis-retinoic acid animals had total tumor regression, but 70% showed partial regression. No tumor regression was found in the DMBA control group and the sham-injected group. PMID- 3108473 TI - Biliary tract surgery in the elderly. AB - Cholecystectomy is the most common surgical procedure in the elderly. Published reports on this operation suffer from small sample sizes, crude analyses, erroneous conclusions, and unsupported recommendations. The authors reviewed all first operations for cholelithiasis at the North Carolina Memorial Hospital from 1973 to 1982 to assess factors associated with postoperative morbidity in patients aged 70 years or older after biliary tract surgery. These elderly patients (n = 142) had more frequent postoperative complications (26.1% vs. 12.0%, p less than 0.0001), and greater mortality (9.2% vs. 2.7%, p less than 0.005) than did 839 younger patients. Patients with preoperative cardiac, renal or neurologic problems had more frequent postoperative complications whether they were old or young. Postoperative complications were more frequent in the elderly for non-emergency surgery (21.2% vs. 9.7%) but not for emergency surgery (44.8% vs. 42.4%). Logistic regression analysis was used to determine independent predictors of postoperative complications. Age greater than or equal to 70 years was associated with an increase in risk that was not statistically significant. PMID- 3108476 TI - Meal-stimulated pepsinogen secretion in premature infants. PMID- 3108475 TI - Treatment of bilateral fracture of the mandible in a hemophilic patient with inhibitor to factor VIII. PMID- 3108477 TI - Effects of the protozoan parasite Sarcocystis rauschorum on open-field behaviour of its intermediate vertebrate host, Dicrostonyx richardsoni. AB - Behaviour and activity levels were measured in varying lemmings experimentally infected with the heteroxenous parasite, Sarcocystis rauschorum to test the hypothesis that the parasite alters behaviour of this intermediate host and thereby increases probability of transmission to the definitive host, the snowy owl (Nyctea scandiaca). Measures of short-term activity levels on a running wheel indicated no effect of the parasite, either directly, or indirectly as a result of illness. We observed behaviour of infected lemmings placed in an "open field" (arena). Lemmings would increase their susceptibility to predators if they spent more time away from cover, used crypsis (stationary postures) less, spent more time exploring (especially in unfamiliar areas), or responded inappropriately to threats from predators. We found that only exploratory activity showed significant change after infection. The frequency of exploratory activity increased and became disassociated from the usual fear response. This may increase the lemmings' susceptibility to aerial predation. The mechanism for this effect is unknown, but neurological lesions have been observed. The examination of the modes of transmission of the S. rauschorum parasite within lemming populations and of a possible fecundity compensation strategy adopted by the lemmings, and their relevance to population control, are suggested as areas for future study. PMID- 3108480 TI - Intestinal permeability to 51Cr-EDTA and 125I-egg albumin in gerbils infected with Trichostrongylus colubriformis. PMID- 3108479 TI - Infection and mortality patterns in strains of oysters Crassostrea virginica selected for resistance to the parasite Haplosporidium nelsoni (MSX). AB - Strains of oysters Crassostrea virginica resistant to mortality caused by the parasite Haplosporidium nelsoni (MSX) were developed and tested through 6 generations. In addition, strains in each generation were followed for up to 6 yr of continuous exposure to the parasite in nature. Selected strains responded to challenge by the parasite with gradually improved survival in successive generations. They were slower to develop patent infections than were unselected groups and were able to delay mortality after infections did develop, but under repeated exposure most oysters eventually died with H. nelsoni parasitism. Many selected strains, however, reached market size before significant mortalities occurred. The data suggest that resistance to H. nelsoni mortality is under the influence of many genes. No clear defense mechanism has been described and we hypothesize that resistance to H. nelsoni may, in part, involve a physiological state in which selected oysters temporarily fail to provide a suitable habitat for the parasite. Temporary insusceptibility would, in this view, be followed by an increased ability to tolerate the parasite when conditions for its development are present. Selection would then favor individuals that are able to prolong periods of insusceptibility and/or to carry out basic life processes while parasitized. PMID- 3108478 TI - Early diagnosis of Schistosoma mansoni in mice using assays directed against cercarial antigens isolated by hydrophobic chromatography. AB - Two diagnostic assays are described for the early diagnosis of acute schistosomiasis, using a defined cercarial antigen preparation obtained by hydrophobic chromatography. Circulating IgM antibodies against this antigen fraction could be detected by ELISA as early as 1 wk after exposure in experimentally infected mice; IgM levels against other antigens and IgG levels against all the preparations examined were not significantly elevated until approximately 4-5 wk postinfection. Circulating antigen was detected as early as 3 days after exposure by a competitive inhibition ELISA using rabbit serum prepared against the cercarial antigen; antigen levels in the serum of mice with a 100-worm infection were found to exceed 100 ng/ml. Studies using sera from infected humans indicate that the assay can also recognize chronic S. mansoni, S. haematobium or S. japonicum infections. In a very limited field study, the specificity of the circulating antigen assay with regard to other helminthic infections was found to be 85%; sensitivity 100%. Preliminary characterization of the relevant antigen indicates that it is a relatively hydrophobic polypeptide with a molecular weight of approximately 41,000 daltons. The implications of these findings with regard to the treatment of travelers or the conduct of seroepidemiological studies in endemic areas are discussed. PMID- 3108481 TI - Culture medium for a continuous source of Trypanosoma cruzi metacyclic forms. PMID- 3108482 TI - Schistosoma mansoni: demonstration of homospecific antibody adsorbed to the tegumental surfaces of adult male parasites from mice. PMID- 3108483 TI - Technique to detect schistosome cercariae in natural water through exposure of sentinel hamsters. PMID- 3108484 TI - Zinc status and its relations to growth retardation in children with biliary atresia. AB - Zinc status was studied in 36 children with biliary atresia and in ten children with Hirschsprung's disease or anorectal anomalies. Changes in preoperative and postoperative plasma and urinary zinc levels were measured in 16 children with biliary atresia and ten children with Hirschsprung's disease or anorectal anomalies. Hypozincemia was evident in children with biliary atresia preoperatively and became severe with time when adequate zinc supplementation was not given. Follow-up studies were done in 20 children with biliary atresia aged between 9 months to 10 years. The children with poor bile excretion and impaired liver function tended to have hypozincemia and a high excretion of zinc. Growth retardation was also common in these children. Careful monitoring and appropriate supplementation of micronutrients, including zinc is probably important for normal growth in children with biliary atresia. PMID- 3108485 TI - Apple peel jejunal atresia. AB - Apple peel deformity of the small bowel is a variant of jejunal atresia with a high mortality. Forty five percent of these patients can be expected to die, most from anastomotic leaks with sepsis, or anastomotic failure with prolonged ileus and malnutrition. This report documents survival of three consecutive patients treated by an adaptation of the Santulli "chimney" anastomosis. This method accomplishes the goals of relief of intestinal obstruction, minimal resection, and preservation of tenuous intestinal blood vessels. All three patients had a benign postoperative course and made an uneventful recovery. Intestinal function is normal in each patient at 1 1/2 years. Based on this experience, it appears that a Santulli jejunojejunostomy combined with total parenteral nutrition offers the most promising operative strategy in the treatment of patients with apple peel bowel. PMID- 3108486 TI - Pharmacological studies on the release of slow reacting substance of anaphylaxis during anti-immunoglobulin E antibody mediated passive peritoneal anaphylaxis in rats. AB - The release of slow reacting substance of anaphylaxis (SRS-A) by anti immunoglobulin E(IgE; epsilon)-antibody mediated passive peritoneal anaphylaxis (PPA) in rats was investigated immunopharmacologically. A significant amount of SRS-A was released by anti-epsilon-antibody in the peritoneal cavity of rats passively sensitized with IgE. The amount of SRS-A released by anti-epsilon antibody was about one third less than that released in an anti-gamma-antibody and IgG2a system. The release of SRS-A was initiated at 2 min and reached its maximum 5 to 10 min after the injection of anti-epsilon-antibody. Disodium cromoglycate, tranilast and ketotifen inhibited the release of both SRS-A and histamine caused by anti-epsilon-antibody mediated PPA. Glucocorticoids (hydrocortisone, prednisolone and dexamethasone) also inhibited the release of both mediators. rho-Bromophenacyl bromide inhibited the release of both mediators. AA-861, a potent 5-lipoxygenase inhibitor, inhibited the release of SRS-A but not histamine. Indomethacin slightly enhanced the release of SRS-A and inhibited the release of histamine. Cytarabine resulted in leucopenia and inhibited the release of histamine but not SRS-A during PPA. Dextran sulfate reduced the number of glass adherent peritoneal cells and inhibited the release of SRS-A but not histamine. These results suggest the suitability of anti-epsilon antibody mediated rat PPA for investigating the effect of anti-allergic agents on the release of SRS-A. PMID- 3108487 TI - Effect of valproic acid on pharmacokinetics of active metabolites of cyclophosphamide in mice. AB - The effects of valproic acid (VPA) on pharmacokinetics of cyclophosphamide (CPM) alkylating metabolites were investigated in male BALB/c mice. The pharmacokinetics of CPM alkylating metabolites was found to be dose-dependent representing the decrease of formation and elimination rates of the metabolites. A nonlinear increase of area under blood concentration of CPM alkylating metabolites-time curve (AUC) occurred with increasing CPM dose of 100, 200, and 300 mg/kg body weight. The effects of VPA (100 mg/kg dose) coadministered with CPM were similar to those of the increase of the CPM dose in preventing the activation of CPM and the elimination of its alkylating metabolites. The delayed disposition of CPM alkylating metabolites resulted in a 1.5-fold increase (p less than 0.02) of AUC which was considered the most important pharmacokinetic parameter in the CPM therapy. VPA which was injected i.p. at a dose of 100, 200, or 300 mg/kg increased the pentobarbital induced-sleep time by 81, 138, or 192%, respectively. In order to assess the effect of VPA on drug metabolizing enzyme(s) activity in humans, the ratio of daily urinary 6-hydroxycortisol to 17 hydroxycorticosteroids, which can reflect cytochrome P-450 activity, was determined in 5 healthy volunteers. The ratio was rapidly and significantly decreased (p less than 0.05) and this reduction continued during VPA administration. These findings and those reported in the literature concerning CPM metabolism suggest that the delay of CPM alkylating metabolites elimination resulted in part from microsomal enzyme(s) inhibition by VPA. PMID- 3108488 TI - Codon usage in streptococci. AB - Codon usage was analysed for 14 streptococcal genes or significant open reading frames and found to be different from that in Escherichia coli and Bacillus subtilis. In particular, the preferred use of WWT codons over WWC was inconsistent with the rule of optimal codon-anticodon interaction energy. On the other hand, for SSTC codons, adherence to this rule was better in streptococci than in E. coli. A preliminary codon bias table generated with the Pustell computer program for the analysed streptococcal genes may prove useful for the detection of protein coding regions in newly sequenced DNAs from both streptococci and staphylococci. PMID- 3108489 TI - Interaction of anthracycline antibiotics with biopolymers: comparative studies of DNA binding and antimicrobial activity of rhodomycin-type anthracycline antibiotics. AB - The binding of the anthracyclines beta-rhodomycin-I and beta-rhodomycin-II to calf thymus DNA was investigated by both equilibrium and kinetic methods taking into account ligand dimerization (ionic strength I = 0.2 M, pH 6.0). The analysis was based upon a cooperative single-step binding mechanism with overlapping of potential binding sites on a linear homogeneous lattice. Equilibrium binding parameters were estimated from spectrophotometric titration experiments by means of a nonlinear fitting program. The results were compared with those obtained previously for the related antibiotic iremycin and were complemented by kinetic parameters determined from temperature-jump experiments at high binding ratio. The binding constants and the mean attachment times of the drugs were found to increase in the serial order iremycin, beta-rhodomycin-I and beta-rhodomycin-II, which is in line with their increasing antimicrobial activity on Bacillus subtilis ATCC 6633. PMID- 3108490 TI - Carbon dioxide laser use in wound sealing and epikeratophakia. AB - This paper presents current clinical and experimental uses of the carbon dioxide laser and the results of our human and animal tissue fusion investigations. Trials were conducted with human scleral and corneal eye bank tissue and in albino rabbits. With power settings of 100 to 200 mW, optimal laser effect consisting of slight whitening and minimal edge shrinkage occurred between 10 and 70 mJ of total energy. No tissue adherence could be demonstrated with the parameters tested. A final study was made on the feasibility of sealing an epikeratophakia lenticle to its recipient bed using the carbon dioxide laser. The average force required to remove the button in the control experiments was 6.45 g and this increased to 6.99 g after laser treatment although no fusion was apparent. This was statistically significant (P less than .05). PMID- 3108491 TI - Rumen ophryoscolecid protozoa in the hindgut of the capybara (Hydrochoerus hydrochaeris). AB - Rumen ophryoscolecid protozoa were observed in feces obtained from two capybara (Hydrochoerus hydrochaeris) housed at the Columbus Zoo, Columbus, Ohio. Total numbers were 58.1 X 10(4) and 19.0 X 10(4) per gram of wet feces in a male and female capybara, respectively. Four common rumen species of Entodinium were observed in the feces from both animals, with low numbers of Eudiplodinium maggii and Elytroplastron bubali also occurring in the male. Establishment of rumen ophryoscolecid ciliates in the intestinal tract of non-ruminant herbivores has not been reported previously. PMID- 3108492 TI - Effects of iron-, manganese-, or magnesium-deficiency on the growth and morphology of Euglena gracilis. AB - Iron-, manganese-, or magnesium-deficiency has been induced in Euglena gracilis. Each arrests cell proliferation, decreases the intracellular content of the deficient metal, and increases that of several other metals. Light and electron microscopy of stationary phase cells reveal that Fe-deficient (-Fe) cells are similar in size and shape to control organisms. Magnesium-deficient (-Mg) cells, however, are larger, and approximately 14% are multilobed, containing 2 to 12 lobes of equal size emanating from a central region. Individual (-Mg) cells and each lobe of multilobed cells contain a single nucleus. Manganese-deficient (-Mn) organisms are morphologically more heterogeneous than (-Fe) or (-Mg) cells. Most are spherical and larger than controls. Approximately 15% are multilobed but, unlike (-Mg) cells, contain lobes of unequal size with either zero, one, or several nuclei present in each. Nuclei of (-Mn) cells differ in size and shape from those of control, (-Fe), or (-Mg) cells. All three deficient cell types accumulate large quantities of paramylon. Other cytoplasmic structures, however, appear normal. Addition of Fe, Mn, or Mg to the respective deficient stationary phase cultures reverses growth arrest and restores normal morphology. The results suggest that Fe-, Mn-, and Mg-deficiencies affect different stages of the E. gracilis cell cycle. PMID- 3108493 TI - Ultrastructural visualization of lipids in trypanosomatids. AB - An imidazole-buffered osmium tetroxide solution was used to visualize lipids at the ultrastructural level in the following members of the family Trypanosomatidae: Trypanosoma cruzi, T. dionisii, T. vespertilionis. T. rangeli, Crithidia deanei, C. fasciculata, C. oncopelti, and Blastocrithidia culicis. Electron-dense material was seen in various lipid droplets found in all parasites and in the multivesicular structure of members of the sub-genus Schizotrypanum. High contrast of some membranes, mainly those which enclose the mitochondrion, the nucleus, and the endoplasmic reticulum, was observed even in unstained sections. X-ray microanalysis confirmed that the electron density of lipid droplets of B. culicis and membrane-bounded dense granules of C. oncopelti was due to the presence of osmium. PMID- 3108494 TI - Aggressive behavior in long-term care. PMID- 3108495 TI - Computer-based medical record systems--have they come of age? PMID- 3108496 TI - Historical development of housing hygiene policy. PMID- 3108497 TI - Future trends in housing hygiene policy. PMID- 3108498 TI - Theoretical considerations and applications of relaxation training for children. PMID- 3108499 TI - Developing primary health care manpower: the Abu Dhabi model. PMID- 3108500 TI - Malaria control in Tanzania. PMID- 3108501 TI - Masturbatory death and injury. PMID- 3108502 TI - Diarrhoeal disease in bottle fed children. PMID- 3108503 TI - Oral rehydration therapy--a review. PMID- 3108504 TI - Effect of stress on performance of high school principals. PMID- 3108505 TI - Marriage break up and the effect on families. PMID- 3108506 TI - Poisoning by arsenic. PMID- 3108507 TI - Levels of blood glucose and intake of food in dogs. PMID- 3108508 TI - Evaluation of performance of radiology residents. PMID- 3108509 TI - Effects of Ascogregarina barretti (Eugregarinida: Lecudinidae) infection on emergence success, development time, and size of Aedes triseriatus (Diptera: Culicidae) in microcosms and tires. PMID- 3108510 TI - Osmotic reversal induces assembly of tight junction strands at the basal pole of toad bladder epithelial cells but does not reverse cell polarity. AB - This paper reports the effect of reversing the osmotic environment between luminal and serosal compartments of a toad urinary bladder on the polarity of assembly of tight junction strands. Toad bladders were filled with Ringer's solution (220 mOsm) and were immersed in distilled water at room temperature or at 37 degrees C. Within two minutes, new tight junction strands are assembled. The new tight junctional strands unite the basal pole of epithelial cells with the apical side of basal cells. Physiological studies show that oxytocin, a synthetic analog of antidiuretic hormone, is still capable of inducing increases in water transport in epithelia which were osmotically reversed. This capacity decreases significantly for longer periods of osmotic reversal. Osmotic reversal does not alter the original polarity of epithelial cells: the apical tight junction belt, at the apical pole, is not displaced; the freeze-fracture morphology typical of apical plasma membrane (particle-rich E faces; particle poor P faces) is not altered; oxytocin and cyclic AMP induce aggregates which are observed only at the apical plasma membrane. Massive assembly of junctional elements occurs even in epithelia preincubated in the presence of cycloheximide (an inhibitor of protein synthesis) or of cytoskeleton perturbers. Our experiments show that the polarity of assembly of tight junction strands depends on the vectorial orientation of the osmotic environment of the epithelium. PMID- 3108511 TI - Intracellular ion concentrations in the frog cornea epithelium during stimulation and inhibition of Cl secretion. AB - The intracellular electrolyte concentrations in the isolated cornea of the American bullfrog were determined in thin freeze-dried cryosections using energy dispersive X-ray microanalysis. Stimulation of Cl secretion by isoproterenol resulted in a significant increase in the intracellular Na concentration but did not change the intracellular Cl concentration. Similar results were obtained when Cl secretion was stimulated by the Ca ionophore A23187. Inhibition of Cl secretion by ouabain produced a large increase in the intracellular Na concentration and an equivalent fall in the K concentration. Again, no increase or decrease in the intracellular Cl concentration was detectable. Clamping of the transepithelial potential to +/- 50 mV resulted in parallel changes in the transepithelial current and intracellular Na concentration, but, with the exception of the outermost cell layer, in no changes of the Cl concentration. Only when Cl secretion was inhibited by bumetanide or furosemide, together with a decrease in the Na concentration, was a large fall in the Cl concentration observed. Application of loop diuretics also produced significant increases in the P concentration and dry weight, consistent with some shrinkage of the epithelial cells. The results suggest the existence of a potent regulatory mechanism which maintains a constant intracellular Cl concentration and, thereby, a constant epithelial cell volume. Through the operation of this system any variation in the apical Cl efflux is compensated for by an equal change in the rate of Cl uptake across the basolateral membrane. Cl uptake is sensitive to loop diuretics, directly coupled to an uptake of Na, and dependent on the Na and K concentration gradients across the basolateral membrane. Isoproterenol and A23187 seem to increase the Cl permeability of the apical membrane and thus stimulate Cl efflux. Ouabain inhibits Cl secretion by abolishing the driving Na concentration gradient for Cl uptake across the basolateral membrane. PMID- 3108513 TI - Chiral phosphorothioate analogues of B-DNA. The crystal structure of Rp d[Gp(S)CpGp(S)CpGp(S)C]. AB - The compound Rp-d[Gp(S)CpGp(S)CpGp(S)C], an analogue of the deoxyoligomer d(G C)3, crystallizes in space group P2(1)2(1)2(1) with a = 34.90 A, b = 39.15 A and c = 20.64 A. The structure, which is not isomorphous with any previously determined deoxyoligonucleotide, was refined to an R factor of 14.5% at a resolution of 2.17 A, with 72 solvent molecules located. The two strands of the asymmetric unit form a right-handed double helix, which is a new example of a B DNA conformation and brings to light an important and overlooked component of flexibility of the double helix. This flexibility is manifest in the alternation of the backbone conformation between two states, defined by the adjacent torsion angles epsilon and zeta, trans . gauche-(BI) and gauche-. trans (BII). BI is characteristic of classical of B-DNA and has an average C(1') to C(1') separation of 4.5 A. The corresponding separation for BII is 5.3 A. Each state is associated with a distinct phosphate orientation where the plane of the PO2 (or POS) group is alternately near horizontal or vertical with respect to the helix axis. The BI and BII conformations are out of phase on the two strands. As a consequence, on one strand purine-pyrimidine stacking is better than pyrimidine-purine, while the converse holds for the other strand. At each base-pair step, good and bad stacking alternate across the helix axis. The pattern of alternation is regular in the context of a fundamental dinucleotide repeat. Re-examination of the B-DNA dodecamer d(C-G-C-G-A-A-T-T-C-G-C-G) shows that the C-G-C-G regions contain the BI and BII conformations, and the associated dual phosphate orientation and asymmetric base stacking. Different mechanisms are used in the two structures to avoid clashes between guanine residues on opposite strands, a combination of lateral slide, tilt and helical twist in the present structure, and base roll, tilt and longitudinal slide (Calladine rules) in the dodecamer. The flexibility of the phosphate orientations demonstrated in this structure is important, since it offers a structural basis for protein-nucleic acid recognition. PMID- 3108512 TI - Intracellular solute gradients during osmotic water flow: an electron-microprobe analysis. AB - In an attempt to quantify possible intracellular water activity gradients during ADH-induced osmotic water flow, we employed energy dispersive X-ray microanalysis to thin, freeze-dried cryosections obtained from fresh, shock-frozen tissue of the toad urinary bladder. The sum of all detectable small ions (Na + K + Cl) in the cellular water space was taken as an index of the intracellular osmolarity. Presuming that all ions are osmotically active, they comprise about 90% of the cellular solutes. When the cells were exposed to dilute serosal medium, the reduction in the sum of the ions agreed well with the expected reduction in osmolarity. After inducing water flow by addition of ADH and dilution of the mucosal medium, all epithelial cells showed a fall in osmolarity. The change was more pronounced in granular cells than in basal or mitochondria-rich cells, consistent with the notion that granular cells represent the main transport pathway. Most significantly, intracellular osmolarity gradients, largely caused by an uneven distribution of K and Na, were detectable in granular cells. The gradients were not observed after ADH or mucosal dilution alone, or when the direction of transepithelial water flow was reversed. We conclude from these results that there is a significant cytoplasmic resistance to water flow which may lead to intracellular gradients of water activity. Concentration gradients of diffusible cations can be explained by a flow-induced Donnan-type distribution of fixed negative charges. With regard to transepithelial Na transport, the data suggest that ADH stimulates transport by increasing the Na permeability of the apical membranes of granular cells specifically. PMID- 3108514 TI - Differential repression of SOS genes by unstable lexA41 (tsl-1) protein causes a "split-phenotype" in Escherichia coli K-12. AB - The lexA41 (formerly tsl-1) mutant was isolated as an ultraviolet light resistant, temperature-sensitive derivative of its ultraviolet light-sensitive lexA3(Ind-) parent. Cells exhibit a so-called "split-phenotype", a phenomenon in which only a subset of the SOS responses can be detected physiologically following inducing treatments. lexA41 has been cloned and sequenced; the mutant gene retains the lexA3 mutation (Gly to Asp at position 85) and has a second mutation, lexA41 (Ala to Thr at position 131). We show that LexA41 protein is not cleaved by the RecA protein-catalyzed pathway in vivo, but the mutant protein is degraded by the Lon protease at both 32 degrees C and 42 degrees C. beta Galactosidase activities of lac fusions to 13 different SOS promoters were measured at 30 degrees C and 42 degrees C to determine levels of expression and were found to vary considerably. The temperature-sensitive phenotype is a result of increased expression of sulA, which encodes a division inhibitor, at 42 degrees C. Excision repair genes, including uvrA, uvrB and uvrD, are constitutively expressed at 30 degrees C accounting for the ultraviolet light resistance of the lexA41 mutant, but the SOS mutagenesis operon, umuD,C, is not adequately derepressed, thereby explaining the failure to induce mutagenesis in this background. This differential expression of SOS genes gives a plausible explanation of the split-phenotype associated with lexA41. PMID- 3108515 TI - Transient hypoglycemic paraparetic syndrome in an elderly patient. AB - An elderly diabetic patient sustained a transient hypoglycemic paraparetic episode that was attributed to inappropriate administration of glyburide. There were no other predisposing causes to account for the transient hypoglycemia. The predominant clinical signs were paraparesis of the lower extremities, with the right side more affected than the left. The patient's paraparesis cleared within two hours after administration of 50 mL of 50 percent glucose intravenously.The management of a paraparetic syndrome should include an appraisal of all the predisposing factors and their correction. The mechanism that was deemed responsible for the patient's transient hypoglycemic paraparetic syndome was loss of cerebrovascular autoregulation in a vulnerable area (the vertebral-basilar artery distribution). In the elderly patient tight control of blood glucose levels should be avoided in view of the potential development of hypoglycemia and brain injury. PMID- 3108516 TI - Antibiotic removal device. PMID- 3108518 TI - Chemotherapy in the control of urinary schistosomiasis in Nigeria. AB - Praziquantel (Biltricide, Bayer AG), which has been found to be very effective in the treatment of schistosomiasis, was evaluated to formulate the minimal cost effective dose in selective chemotherapy of 135 school children aged 6-15 years. Side effects were minimal. The drug had no effect on the heavy load of intestinal helminths found in 78.1% of the subjects. However, it cleared the urinary schistosomiasis in all but 0.9% of the subjects at the dosages used and after 18 months only 0.59% of the entire school population had new infections. The targetted chemotherapy reduced the prevalence rate from 16.0% to 0.59%. The lowest dose of 1 X 20 mg/kg body weight was able to clear the light infections of 52 subjects. This has a great economic advantage because the drug is expensive and most of the infections in Nigeria are light to moderate. PMID- 3108517 TI - In vivo and in vitro absorption and binding to powered stratum corneum as methods to evaluate skin absorption of environmental chemical contaminants from ground and surface water. PMID- 3108519 TI - Total parenteral nutrition (TPN) and gallbladder diseases in neonates. Sonographic assessment. AB - During a 1-year period, a prospective ultrasound (US) study of the biliary tract was performed in 41 neonates receiving total parenteral nutrition (TPN). Gallbladder sludge appeared in 18 neonates (44%) after a mean period of 10 days of TPN. The occurrence of this abnormality seems related to three main factors: prematurity with immaturity of the enterohepatic circulation of bile acids, duration of TPN, and lack of enteral nutrition. In five neonates (12%), an evolution of sludge to "sludge balls" was observed. Two neonates (5%) went on to develop uncomplicated gallstones and a spontaneous resolution occurred in one of them 6 months after the examination. This finding suggests conservative management in such cases. However, since cholecystitis or biliary tract obstruction are classical complications in older children, a US survey of neonates receiving TPN is useful to follow the abnormal gallbladder content, and rapid introduction of enteral feeding is advisable. PMID- 3108520 TI - Pharmacokinetics of phenoxymethyl penicillin (penicillin V) in calves. AB - Phenoxymethyl penicillin (penicillin V) was administered intravenously (i.v.) and orally to pre-ruminant calves and the distribution and elimination kinetics, as well as the oral bioavailability, were determined. After i.v. injection, the drug was distributed rapidly in the body, the elimination half-life (t1/2 beta) was 34 min and the apparent volume of distribution at steady-state (Vd ss) was 0.30 l/kg. Mean peak serum drug concentrations were directly related to the oral dose administered, i.e. 0.22 microgram/ml, 1.06 micrograms/ml and 2.14 micrograms/ml after dosing at 10, 20 and 40 mg/kg, respectively. The elimination t1/2 of the drug after oral dosing varied between 90 and 110 min, and the oral bioavailability was approximately 30% of the dose. The co-administration of phenoxymethyl penicillin and probenecid resulted in elevation and prolongation of serum drug concentration. The percentage of drug bound to serum proteins was 78.8% +/- 8.2%. Phenoxymethyl penicillin was probably inactivated and degraded in the gastrointestinal tract of 6-week-old calves fed exclusively hay, silage and concentrates as very low and erratic serum drug concentrations were measured after these calves were dosed orally with the drug at 40 mg/kg. In view of the narrow antibacterial spectrum of the drug and the relatively high dose required, it appears that phenoxymethyl penicillin can only be of limited practical value for the treatment of bacterial infections in preruminant calves. PMID- 3108521 TI - Effect of different intervals between dosing and feeding on systemic availability of penicillin V in dogs. PMID- 3108522 TI - Ultrastructure of Sarcocystis spp. (Protozoa: Apicomplexa) in rodents from North Sulawesi and West Java, Indonesia. AB - Tissue cysts of the protozoan genus Sarcocystis were detected in the skeletal muscles of 16 (40%) of 40 wild rodents captured in North Sulawesi and West Java, Indonesia. Two types of cysts were found to differ in their morphological characteristics. Macroscopic and microscopic cysts bounded by thick radially striated cyst walls were detected at both locations in a total of 13 rodents belonging to seven different species (Bunomys chrysocomus, B. fratrorum, Maxomys bartelsii, M. musschenbroekii, Paruromys dominator, Rattus xanthurus and R. exulans). The primary cyst walls contained numerous broad spatula-like protrusions and the cysts were identified as S. singaporensis Zaman and Colley, 1976. In contrast, microscopic cysts bounded by thin smooth cyst walls were detected in seven rodents belonging to three different species captured at Toraut in North Sulawesi (B. chrysocomus, B. fratrorum and P. dominator). Ultrastructural examination revealed numerous slender hair-like protrusions of their primary cyst walls. It is proposed that these cysts be named S. sulawesiensis sp. n. on the basis of their unique morphological characteristics, their intermediate host range and their limited geographic distribution. Mixed infections by both species were found in three rodent species (B. chrysocomus, B. fratrorum and P. dominator). PMID- 3108523 TI - Septicemic listeriosis in a reindeer calf. AB - Septicemic listeriosis is described in a 2-day-old reindeer calf (Rangifer tarandus tarandus) from a local zoo. The gross and microscopic lesions were typical of disease caused by bacterial septicemia. Major lesions included necrosis of the liver, lung, adrenal gland, spleen, and lymph node. The diagnosis was suspected by special histopathological stains and confirmed by isolation of Listeria monocytogenes from multiple organs. This is the first report of listeriosis in a reindeer. PMID- 3108524 TI - Listeriosis in an immature black buck antelope (Antilope cervicapra). AB - A 10-week-old, black buck antelope calf, from the Mesker Park Zoo in Evansville, Indiana was found dead without observed signs of illness. Necropsy disclosed disseminated ecchymoses on the pericardium, diaphragm, intestines, and renal capsules and more extensive hemorrhage in the muscles of the hindquarters. There were numerous, 1 mm, pale foci on the capsular and cut surfaces of the liver and spleen which, on microscopic examination, were necrotic foci containing variable numbers of neutrophils and mononuclear leukocytes with numerous, short, Gram positive, cocco-bacilli at the periphery. Listeria monocytogenes was isolated from the liver. Septicemia is the most common form of listeriosis in non-domestic ruminants. Listeriosis should be suspected when unexpected deaths are accompanied by multifocal necrotizing hepatitis and splenitis, myocarditis, and disseminated hemorrhage. PMID- 3108525 TI - Error in hematocrit of EDTA-preserved whole blood from black bears caused by delayed analysis. AB - Hematocrit values for K3EDTA-preserved whole blood from black bears (Ursus americanus) were found to increase during refrigerated storage causing error in delayed laboratory analysis. This error was quantified using a regression type model based on repeated hematocrit testing of 66 blood samples over time. The model proved to fit quite well and provided corrected-to-day-zero hematocrit values for 42 samples from which day-zero values were not available. PMID- 3108526 TI - Heart/lung recipient becomes first living heart donor in United States. PMID- 3108527 TI - The effect of CS-514 on serum lipids and apolipoproteins in hypercholesterolemic subjects. AB - CS-514 is a metabolic product of compactin and has a potent cholesterol-lowering effect in vitro and in animal studies by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase. The efficacy and adverse effects of the agent were studied in 41 hypercholesterolemic subjects by administering daily doses of 5, 20, or 40 mg for four weeks under double-blind conditions. Mean total serum cholesterol level was reduced by 11.1% in the 5-mg group, 18.8% in the 20-mg group, and 25.3% in the 40-mg group. Marked reduction of total serum cholesterol level was also observed in heterozygous familial hypercholesterolemics. Mean low-density lipoprotein cholesterol level and apolipoprotein B concentration decreased by 38.5% and 28.8%, respectively, in the 40-mg group, while high-density lipoprotein cholesterol level increased by 11.8%. No serious clinical and laboratory abnormalities were observed. Plasma cortisol and testosterone levels were not significantly affected. These results suggest that CS-514 will be a useful agent in the treatment of nonfamilial and heterozygous familial hypercholesterolemia. PMID- 3108528 TI - The use of claims data to evaluate health care. PMID- 3108529 TI - Hypokalemic respiratory arrest in diabetic ketoacidosis. PMID- 3108530 TI - Method for evaluating utilization of infused oligosaccharides in postsurgical patients. AB - Oligosaccharides are potential sources of carbohydrate-derived energy for use in parenteral nutrition regimens. Clinical studies indicate that although some patients utilize infused oligosaccharides well, many patients do not. These results suggest that oligosaccharides might be useful as a parenteral energy source for selected patients. This report describes a method, suitable for use by nursing staff on the ward, to determine oligosaccharide utilization and identify patients utilizing oligosaccharides well. Oligosaccharides excreted in urine are hydrolyzed enymatically to glucose using alpha-glucosidase and alpha-amylase, and the glucose released is measured by a test tape method. The results obtained agree well with the acid hydrolysis-spectrophotometric assay for oligosaccharide excretion used in earlier studies. The method readily identified postsurgical patients utilizing infused oligosaccharides poorly in both prospective and retrospective studies. PMID- 3108531 TI - Assessing the efficacy of intravenous nutrition in general surgical patients: dynamic nutritional assessment with plasma proteins. AB - We have compared the direction of changes in four plasma transport proteins measured weekly with the direction of nitrogen balance in general surgical patients receiving intravenous nutrition (IVN). Fifty four patients had IVN for 2 weeks, and 15 had IVN for 3 or 4 weeks. Change in plasma prealbumin followed the direction of nitrogen balance in both weeks of IVN in 39 of 54 of the former group, whereas none of the other plasma proteins achieved 50% accuracy. A weekly rise in plasma prealbumin had a sensitivity of 88%, specificity of 70%, positive predictive value of 93%, and negative predictive value of 56% in detecting positive nitrogen balance. Results in the patients who received 3 or 4 weeks of IVN showed an improvement in negative predictive value to 79%. None of the other plasma proteins performed as well. Twelve patients suffered a major complication of their disease or died, following their course of IVN. Nitrogen balance was the best prognostic indicator of these patients, whereas a fall in prealbumin was the best of the plasma proteins, with a sensitivity of 67%, specificity of 79%, positive predictive value of 40%, and negative predictive value of 92% in determining the incidence of complications. Prealbumin was the most suitable plasma protein for use as a dynamic index of nutritional progress in the type of patient seen in this study. PMID- 3108532 TI - The effect of nutritional status on morbidity after elective surgery for benign gastrointestinal disease. AB - The effect of nutritional status on the morbidity and mortality of major gastrointestinal surgery for benign disease was studied in 32 patients. Malnutrition was defined as a serum albumin less than 3.5 g/dl and a recent weight loss greater than 10%, in addition to any two of the following: weight for height, midarm circumference or triceps skin-fold thickness less than 10th percentile. The morbidity and mortality in the 17 malnourished patients was 59% and 29%, respectively, compared with 20% and 7% in 15 well-nourished patients matched for age and operative procedure (p less than 0.05). After operation, the mean duration of inadequate oral nutritional intake period (IONIP, defined as a caloric intake greater than 60% requirement) was 11.9 days +/- 2.9 (SEM) in well nourished patients compared with 30.5 days +/- 3.7 in the malnourished group. The longer IONIP in malnourished patients was a consequence of the higher morbidity in this group, thus warranting the consideration of supportive (postoperative) parenteral nutrition in malnourished patients who undergo major gastrointestinal surgery for benign disease. PMID- 3108533 TI - A comparison of serum transferrin and serum prealbumin as nutritional parameters. AB - Serum transferrin and prealbumin levels were determined at intervals of 3 to 4 days in 16 patients requiring nutritional support. Caloric and nitrogen intake were measured and nitrogen balance calculated. There were 117 intervals available for analysis. A mean decrease in transferrin of 12.95 mg/dl was associated with a mean decrease in nitrogen balance of 0.92 g/day, whereas a mean increase in transferrin of 21.04 mg/dl was associated with a mean increase in nitrogen balance of 1.49 g/day; the correlation between changes in transferrin with changes in nitrogen balance was statistically significant (p = 0.02). Upward and downward changes in prealbumin were also associated with corresponding changes in nitrogen balance, but the changes were not statistically significant. Decreases in transferrin and prealbumin were also associated with a lower caloric intake. Operation caused a significant decrease in prealbumin (p = 0.003) and nitrogen balance (p = 0.05); a decrease in transferrin also occurred, but was not statistically significant. There was a highly significant correlation between serum transferrin and prealbumin (p = 0.001) and also between the interval changes in transferrin and prealbumin (p less than 0.001). In conclusion, transferrin was found to correlate closely with prealbumin. Changes in transferrin were more significantly related to changes in nitrogen balance, and from the results of this study, measurement of serum transferrin can be recommended as a useful parameter in following the nutritional status of patients receiving nutritional support. PMID- 3108534 TI - A comparison of two 20% lipid emulsions. AB - Two different soy oil emulsions (Intralipid and Soyacal) were studied over a 2 week period in a random crossover study to determine if there were clinical or biochemical differences between the two preparations when used in patients requiring total parenteral nutrition (TPN). Each fat emulsion was infused randomly over 1 week and then switched to the other. Eighteen adult patients requiring a minimum of 14 days TPN were studied. None of the 26 metabolic parameters evaluated was statistically different between the two groups. Analysis of nutritional status, irrespective of lipid infused, showed that the patients who received 56 kcal/kg/day with 37% of the nonprotein calories from lipids (1.8 +/- 0.7 g/kcal/day) were in positive nitrogen balance on 80 of the 101 days studied. No adverse effects could be observed from either lipid emulsion during the short period of TPN used in this study. Both lipid emulsions were efficacious as a caloric source, and no clinical complications or biochemical abnormalities were found from either preparation. PMID- 3108535 TI - Carcass and organ composition of rats fed high fat total parenteral nutrition. AB - Fat-based total parenteral nutrition (TPN) has been shown to maintain the host nutritionally equivalent to carbohydrate-based TPN in a rat model; however, data on body composition have not been obtained. This study compared the effects of a lipid-based TPN regimen to those of an isocaloric glucose-based regimen and an oral diet on the composition of the carcass and organs of tumor- and nontumor bearing rats. Sprague-Dawley rats implanted with the Walker 256 carcinosarcoma were randomly assigned to either diet A, a glucose-based TPN regimen; B, a lipid based TPN regimen; or C, a purified oral diet. Tumor-bearing rats infused with diet B had less protein and more fat in their carcasses than those in the other dietary groups. Organs of nontumor- and tumor-bearing rats fed diet B contained less protein and more fat and triglycerides than rats fed either diet A or C. Survival index and hematocrit values were lowest in rats infused with the parenteral lipid diet. These findings indicate an abnormal pathological response to a TPN diet formulated to deliver 67% of nonprotein kilocalories as lipid. PMID- 3108536 TI - Junctional care: the key to prevention of catheter sepsis in intravenous feeding. AB - Investigation of an outbreak of infection related to intravenous feeding catheters, predominantly with Staphylococcus epidermidis, suggested that the probable origin was the connections in the delivery system. Equipment and policy changes were then instituted: a catheter with integral hub was used, the connections were reduced from two to one, and improved antisepsis at the connection was devised. These actions resulted in a sustained, significant reduction in the catheter sepsis rate, supporting the hypothesis that junctional care is vital to the avoidance of catheter infection. PMID- 3108538 TI - The potential toxicity to neonates of multivitamin preparations used in parenteral nutrition. AB - This study compares two groups of infants weighing less than 1500 g at birth. In the propylene glycol (PG) group, 30 infants received MVI-Concentrate containing 300 mg of PG daily with their intravenous nutrition (ivn), and vitamin E, 50 mg/week by intramuscular injection. In the mannitol group, 30 infants received MVI-Pediatric (containing 245 mg mannitol), 65% of a vial/day. Serum and urine osmolality, serum PG, blood-urea-nitrogen, creatinine, sodium, and glucose were measured on days 0, 2, 5, 12, 19, 26, 33 and 40 of ivn. Weight, urine output, and fluid intake were measured daily. Vitamin E levels were measured on days 5, 26, and 33 of ivn. There were no significant differences between the groups in birth weight, gestational age, sex, age, or weight at start of ivn. Our results indicated that neither MVI-Concentrate nor MVI-Pediatric was associated with a clinically significant diuresis. MVI-Pediatric, 65% of a vial/day, may produce higher than desirable blood levels of vitamin E, and use of drugs containing PG can produce significant blood levels of PG, in very low birth weight infants. PMID- 3108537 TI - Relationship of antioxidant enzymes to trace metals in premature infants. AB - Serum levels of the trace metals copper, zinc, and selenium were measured in premature infants. White blood cell glutathione peroxidase and superoxide dismutase levels were measured in conjunction with the trace metals. Three groups of infants were evaluated: group I was relatively healthy, group II were infants with stage 2 bronchopulmonary dysplasia (BPD) or less, group III were infants with stage 3 BPD or worse. Zinc and selenium levels declined in all groups during conventional parenteral nutrition (TPN) regimens, while copper remained stable. Copper did decline in groups I and II coincident with an acceleration in growth rate. An expected rise in antioxidant enzyme levels in infants with pulmonary oxygen toxicity was not seen. This study suggests that supplemental selenium as well as an increased zinc intake over current recommendations for premature infants receiving TPN may be indicated. PMID- 3108539 TI - Vitamin D requirement in infants receiving parenteral nutrition. AB - The adequacy of low dose vitamin D (25 IU/dl) parenteral nutrition (PN) solution was studied in 18 infants. All infants had surgical indications for PN. The birth weights were 2810 +/- 135 g and gestational ages 37.4 +/- 0.5 wk (mean +/- SEM). Duration of study ranged from 5 to 175 days. Thirteen infants were studied for up to 6 weeks and five infants for 71 to 175 days. Results showed that studied infants maintained growth along normal percentiles for weight, length, and head circumference. Vitamin D status as indicated by serum 25 hydroxyvitamin D (25 OHD) rose from 15 +/- 1.9 ng/ml to 26 +/- 2.8 ng/ml, mean +/- SEM (p less than 0.001) after 9 days, and remained normal up to 6 months. Five infants with biochemical liver dysfunction also had normal serum 25 OHD concentrations, indicating the hepatic 25 hydroxylation process was not severely impaired. Serum total and ionized calcium, phosphorus, and vitamin D-binding protein concentrations were normal. Serum magnesium was mildly elevated in five infants (2.6 to 3 mg/dl) on one occasion and resolved spontaneously. Serum alkaline phosphatase (AP) concentrations rose above baseline values in 12 of 17 infants, but remained within normal range (less than 400 IU/liter at 30 degrees C). Another infant with markedly elevated AP values died from liver dysfunction. Radiographs of the forearms were normal except for marked demineralization in one infant in spite of normal 25 OHD concentrations. We conclude that 25 IU vitamin D/dl of nutrient infusate is adequate to maintain normal vitamin D status, as indicated by normal serum 25 OHD concentrations in infants receiving PN for as long as 6 months. PMID- 3108540 TI - The effect of selenium supplementation on selenium status of patients receiving chronic total parenteral nutrition. AB - Patients receiving long-term total parenteral nutrition (TPN) are at risk for selenium deficiency. The purpose of this study was to determine the effect of parenteral selenium as selenious acid on the selenium status of seven long-term TPN patients. Patients received a dosage of zero, 80, or 160 micrograms Se/day for 1 month each. The measures of selenium status used were selenium levels in plasma and glutathione-peroxidase activities in erythrocytes and platelets. Urinary selenium excretion was measured. Control subjects were selected to match the sex, age, and weight of the patients. With increasing levels of parenteral selenium, there was increasing plasma selenium concentration as well as erythrocyte and platelet glutathione-peroxidase activity. There was no statistical difference between the patients during the time they received the 160 micrograms parenteral selenium treatment and the control subjects for platelet glutathione-peroxidase activity. At the 160 micrograms Se/day level, patient plasma selenium concentrations increased from 28% to 58% of the control levels. Four patients were studied after they returned to the 80 micrograms parenteral selenium/day from the 160-micrograms Se/day treatment. With decreasing parenteral selenium, three patients had decreasing platelet glutathione-peroxidase activity, while plasma selenium concentration decreased in two patients. These data suggest that some patients receiving long-term parenteral nutrition should receive parenteral selenium. PMID- 3108541 TI - Compatibility of medications with enteral feedings. AB - Administration of medications to patients with nasogastric tubes has traditionally been done in a bolus fashion. An alternative to this would be to mix the medications in the continuous drip enteral feeding with subsequent continuous administration. The purpose of this study was to determine the compatibility of select medications with Ensure, Ensure Plus, and Osmolite. We observed neither visible abnormalities in the mixtures nor change in pH of the enteral products after the addition of digoxin, theophylline, phenytoin, methyldopa, or furosemide. The addition of theophylline to all three enteral products caused a substantial increase in the osmolality. We also examined the concentrations of the mixtures to detect any changes occurring over the 12-hr infusion time. A wide variation in concentrations after the addition of phenytoin suspension was corrected by adding the injectable form to the enteral products. Digoxin and furosemide concentrations were essentially unchanged; however, the methyldopa concentration decreased up to 23% over the 12-hr study period. We, therefore, cannot recommend the addition of theophylline, phenytoin suspension, or methyldopa to the three enteral products tested. PMID- 3108542 TI - Inadvertent dislodgement of nasoenteral feeding tubes: incidence and prevention. AB - The introduction of soft, small-bore nasoenteral feeding tubes has improved our ability to provide nutritional support to patients in a more comfortable, safe, and cost-effective manner. A retrospective study reveals, however, that 40% of patients receiving nasoenteral tube feeding experienced inadvertent dislodgement of their feeding tubes. All of the patients with dislodged feeding tubes were confused, disoriented, or obtunded periodically. Various means for preventing this problem are discussed. In view of both the considerable time and effort required to place nasoenteral feeding tubes properly and the potential complications due to inadvertent tubes dislodgement, it is recommended that nasoenteral feeding tubes be secured more effectively, particularly in confused or obtunded patients. PMID- 3108543 TI - Central venous catheter care in parenteral nutrition: a review. AB - Central venous catheter care in parenteral nutrition has been described in numerous publications. These descriptions include care of both short- and long term catheters. Important aspects in the prevention of infection in central venous catheters used for parenteral nutrition have included: the method of central venous access, subcutaneous tunneling, dressing change techniques, therapeutic uses of the catheter, and catheter-intravenous tubing connection care. Methods of predicting infection and evaluating catheter sepsis have been described. The efficacy of intervention by specialized nutrition support teams in infection control related to these catheters has been demonstrated. Newer partially implantable and completely implantable venous access devices have been used for parenteral nutrition. Methods of infection control and prevention of mechanical damage of these types of catheters have been examined with various results. Care and composition of central venous catheters have been shown to have some role in thrombus formation in the central veins. The use of heparin to prevent thrombosis and catheter occlusion, and the varying degrees of success obtained, have been described. Medical treatment of the occluded catheter with urokinase may be a necessary alternative to discontinuance of that catheter. Overall consideration of research methods used to reach conclusions for catheter care should be considered in the evaluation of appropriate care in each situation. PMID- 3108544 TI - Perforation of the small bowel after insertion of feeding jejunostomy: a case report. AB - Feeding jejunostomy has become a useful method of feeding many patients with upper digestive tract dysfunction from a variety of causes. Although problems infrequently do occur with the tube itself, such as dislodgement or obstruction, most patients tolerate the procedure well. We report here a case of perforation of the jejunum that was caused by the tube itself and required reoperation. As with many problems in surgery, careful attention to technical details should help prevent this and other problems after feeding tube insertion. PMID- 3108545 TI - Parenteral nutrition in a pregnant cystic fibrosis patient. AB - This case report describes a 30-year-old pregnant woman with cystsic fibrosis who had marasmus as evidenced by clinical examination. The patient was maintained on central venous hyperalimentation for 18 days in her last trimester. The patient delivered a full-term infant via cesarian section with Apgar of 8 and 9, at 1 and 5 minutes, respectively, and adverse affects. PMID- 3108547 TI - Delayed pneumothorax: a complication of subclavian vein catheterization. PMID- 3108546 TI - Parenteral nutrition-associated cholestasis: recovery following phenobarbitone. AB - A case is presented of a very preterm neonate who developed severe cholestatic jaundice in association with prolonged parenteral nutrition. The effects of a therapeutic trial of phenobarbitone on bilirubin and liver enzymes are shown. This case suggests that phenobarbitone may have a role to play in the treatment of this condition, which is contrary to indications in a few other case reports in the literature. PMID- 3108548 TI - Choledochal cyst--report of 4 cases. PMID- 3108549 TI - Shattered rectum--a simple method of repair. PMID- 3108550 TI - Screening for antibodies to HTLV-III/LAV in our population. A word of caution. PMID- 3108551 TI - Low cost nutritional assessment of surgical patients in Third World countries. PMID- 3108552 TI - Hyperuricemia and correlates in coronary heart disease. PMID- 3108553 TI - Family study of children with fever and fits--clinical and E.E.G. pattern. PMID- 3108554 TI - Potential pathogenic mechanisms of animal-passed virulence-enhanced strains of Campylobacter jejuni/coli. PMID- 3108555 TI - The Mikamo lecture. Tomographic assessment of myocardial perfusion and metabolism in the evaluation of coronary thrombolysis. AB - Although coronary thrombolysis with fibrinolytic agents leads to restoration of patency of coronary arteries demonstratable angiographically, elucidation of the efficacy of the approach requires evaluation of its effect on the heart. Clot selective fibrinolytic agents such as tissue-type plasminogen activator (t-PA) offer particular promise as therapeutic agents because they induce clot lysis without marked activation of the fibrinolytic system in the circulating blood and hence without marked fibrinogenolysis and predisposition to bleeding. Results of several large scale clinical trials demonstrate recanalization in approximately 75% of patients. Detection of recanalization may be achievable by analysis of plasma creatine kinase isoforms as a function of time, and in the research environment, with the use of positron emission tomography. This modality demonstrates restoration of regional perfusion and intermediary myocardial metabolism and provides an approach for calibration of conventional and more widely applicable diagnostic procedures such as scintigraphy. PMID- 3108556 TI - [Anesthetic management of a patient with platelet cyclo-oxygenase deficiency]. PMID- 3108557 TI - [A case report of hyperlipemia with giant fatty liver during adjuvant endocrine therapy by tamoxifen]. AB - A 36-year-old woman was treated with tamoxifen for lung metastasis of breast cancer and had marked hyperlipoproteinemia with giant fatty liver, high plasma triglyceride levels (3673 mg/dl), and increased levels of very low density lipoprotein (VLDL) and intermediate density lipoprotein (UDL). A low level of activity of both plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) was also noted. Our observations support the concept that, in some patients, the weak estrogen-like activity of tamoxifen is amplified and, in severe lipemia, reduction of the activities of LPL and HTGL might impede the conversion of VLDL to LDL, thus causing the amplification of the effect. PMID- 3108558 TI - [Synergistic antiproliferative effect of DFMO in combination with beta-interferon on human gastric cancer in vitro]. PMID- 3108559 TI - [Combined heart-lung transplantation in the Japanese monkey]. PMID- 3108560 TI - [Heart-lung transplantation--preservation and immunologic monitoring]. PMID- 3108561 TI - Immunoglobulin M and G immune response to Leucocytozoon caulleryi in chickens. PMID- 3108562 TI - Development of Theileria sergenti in the midgut of the tick, Haemaphysalis longicornis. PMID- 3108564 TI - [Disorders of hormonal regulation in ischemic heart disease]. AB - Levels of some hormones and their contribution to coronary heart disease (CHD) were examined in a representative (1470-strong) sample of a population of 20- to 69-year-old males. Blood follicle-stimulating hormone and luteinizing hormone levels were shown to increase with age, while the level of somatotrophic hormone remained unchanged, that of testosterone declined, while insulin and estradiol were also on the increase. Disorders of hormonal control contributed essentially to CHD. It is demonstrated that hormonal disturbances may enhance the effects of other coronary risk factors. PMID- 3108563 TI - Effects of L-histidinol on the susceptibility of P815 mastocytoma cells to selected anticancer drugs in vitro and in DBA/2J mice. AB - The effects of L-histidinol on the susceptibility of the transplantable murine mast-cell neoplasm P815 mastocytoma to selected anticancer drugs have been evaluated on cells growing in culture and in syngeneic DBA/2J mice. Combinations of L-histidinol and anticancer drugs of either phase specificity [cytarabine (ara C) and vinblastine sulfate] or cycle specificity [5-fluorouracil (FUra) and methotrexate] had diverse effects on cultured mastocytoma cells as scored by clonogenic cell survival assays. Flow cytometric analysis of randomly proliferating P815 mastocytoma cells revealed that although exposure to L histidinol did not preclude cells from traversing the cell cycle, the analogue nonetheless conferred a dose-dependent and apparently nonspecific delay of cell cycle transit. DBA/2J mice bearing intraperitoneal P815 mastocytoma cells were used to evaluate the in vivo efficacy of L-histidinol-ara-C and of L-histidinol FUra combinations. Quantitative cell survival assays of murine bone marrow cells and of clonogenic tumor cells obtained from treated animals demonstrated that L histidinol eliminated the bone marrow toxicity otherwise attending the use of the drugs ara-C and FUra. Simultaneously, the inclusion of L-histidinol provided a statistically significant increase in the capacity of these two anticancer drugs to eradicate intraperitoneal mastocytoma cells. PMID- 3108565 TI - [Experience with the use of nitroderm--a prolonged-action nitroglycerin preparation]. PMID- 3108566 TI - Schistosomal specific nephropathy leading to end-stage renal failure. AB - In this study 17 patients, 11 with end-stage renal failure and six with nephrotic syndrome were selected. The selection criteria were presence of active intestinal schistosomiasis and absence of any surgical or other medical disease which could explain the renal disease. When examined by light microscopy, kidney biopsies showed membranoproliferative glomerulonephritis in nine, membranous in four, focal segmental glomerulosclerosis in two, sclerosing glomerulonephritis in one case, and no changes in another case. Direct immunofluorescence showed IgG deposits in 13 cases, IgM in 10 and different complement components (C3, C1q) in eight cases. Eluates from the kidney biopsies of the 17 schistosomal as well as six control cases were examined by ELISA against schistosoma mansoni adult worm antigen (AWA). This test showed the presence of antibodies against the AWA in 12 out of 17 of the schistosomal cases, and zero out of six of the controls. When examined by direct IFA using sheep anti-circulating anodic antigen/FITC and by indirect IFA using monoclonal antischistosomal CAA IgG3, kidney biopsies of the ELISA positive cases showed granular deposits of circulating anodic antigen (CAA). We conclude that schistosomal specific nephropathy does exist in the clinical settings and can lead to end-stage renal disease, with CAA probably being a major responsible antigen. PMID- 3108567 TI - [Mixtures for enteral feeding in surgery of gastrointestinal tract (review of the literature)]. PMID- 3108568 TI - [Protein malnutrition in pediatric patients with oncologic diseases]. AB - To study the frequency of protein-caloric malnutrition in children (n = 16) with malignant diseases, we measured serum-albumin, -transferrin, -prealbumin and retinol-binding protein (Radial immunodiffusion) before treatment was started. In 9 children at least 3 of the 4 rapid-turnover proteins were below the age specific reference values. 7 patients (44%) with low rapid turnover proteins were free from infection, liver and renal dysfunction and thus, diagnosis of protein caloric malnutrition was established. Anthropometric parameters as weight for age and the weight/height ratio did not predict protein-caloric malnutrition. Nutritional therapy (enteral, parenteral) during a period of 2 weeks resulted in significant increase of albumin (p less than 0.05), prealbumin (p less than 0.01) and retinol-binding protein (p less than 0.01). Rapid turnover proteins can be easily measured in each laboratory and are useful in diagnosis and treatment of protein-caloric malnutrition of children with malignant diseases as long as the limitations of this method are not neglected. PMID- 3108569 TI - [Prolactin--a diagnostic aid in cerebral seizures]. AB - Prolactin concentration was measured 20 minutes after each seizure in 8 patients with grand mal, 2 patients with complex partial seizures and 5 patients with petit mal seizures. In the group of grand mal and complex partial seizures serum prolactin showed markedly increased levels. After petit mal seizures there was no change in serum prolactin concentration. The possible causes for changes in serum prolactin after a seizure in children are discussed. PMID- 3108572 TI - [Vaccination helps--vaccination protects: the importance of vaccines]. PMID- 3108570 TI - [Ambulatory long-term prevention of thromboembolism with low-molecular weight heparin]. AB - Patients with severe bleeding complications and other side effects on conventional anticoagulants and strong indication for further anticoagulation were treated with a low molecular weight heparin fragment (Tedelparin). In this paper we report the experiences in 30 patients, who were anticoagulated 1-11 months with this compound. All patients injected themselves a dose ranging from 1 X 2,500 to 1 X 20,000 anti factor Xa units per day. Within 132 months of treatment one patient with good compliance developed thromboembolism. Four patients had bad compliance. Two of them experienced rethrombosis 1 and 8 weeks after starting therapy. Severe haemorrhages did not occur. Two patients had one minor bleeding complication each. Both patients developed several times per year severe haemorrhages with conventional anticoagulants. All excessive subcutaneous haematomas and indurations of the adipose tissue at the injection site of conventional heparin disappeared completely. Low molecular weight heparin can be regarded as an alternative anticoagulant in patients with severe bleeding and other complications on oral anticoagulants and conventional heparin. PMID- 3108573 TI - [Vaccination before foreign travel]. PMID- 3108571 TI - [Gamma 1 heavy chain disease with immune vasculitis and rheumatoid arthritis]. AB - We are reporting about a case of gamma heavy-chain disease (Franklin's disease) with immunovasculitis and rheumatoid arthritis. The diagnosis was confirmed by the results of immunoelectrophoresis of the patient's serum and also by evidence of stimulated lymphocytes without light chain, but having gamma heavy-chain surface proteins. The immunofixation of the serum showed two protein bands of gamma heavy-chains with different loads. These results are confirmed by a two dimensional electrophoresis and isoelectric focussing of the serum proteins. The pathologic protein consists of at least two different heavy-chain proteins (mol wt 40,000 and 80,000) with isoelectric points between pH 5.5 and 7.3. In the urine of the patient pathological gamma heavy chain-protein was found only in a very low concentration. The predominant clinical symptom of the patient was a necrotizing vasculitis which became a therapeutical problem. In the immunofluorescence examination of the skin biopsy specimens, immunoglobulins and C3-complement could be detected in the stratum papillare. This fact would be compatible with the development of antibodies or immune complexes against deposited heavy-chain proteins. The arthropathy and the positive rheumatoid factor could similarly be explained by an immune complex mechanism. PMID- 3108574 TI - [Report on experiences during employment at the Christian Medical College and Hospital in Vellore, southern India. 1]. PMID- 3108575 TI - [The importance of vaccination for our children's health]. PMID- 3108576 TI - [Nursing report during the 1st year of training]. PMID- 3108577 TI - [1st long-term nursing home in the Federal Republic--the hospice "Haus Horn" in Aachen]. PMID- 3108578 TI - [A German male nurse in Iceland. Report of experiences]. PMID- 3108579 TI - [We introduce: self-help group scleroderma. Scleroderma--what is it?]. PMID- 3108580 TI - Fecal microflora of marmosets with wasting marmoset syndrome. PMID- 3108581 TI - Causative factors for decreased pulmonary metastasis in parenterally fed mice. AB - Total parenteral nutrition (TPN) with fat and/or glucose as the caloric source is associated with a decrease in pulmonary metastasis in mice bearing subcutaneously implanted Lewis lung carcinoma. Five groups of white mice bearing Lewis lung carcinoma were assigned to receive various isocaloric and isonitrogenous oral and parenteral feedings: TPN, utilizing all nonnitrogen energy from glucose; per os, utilizing all nonnitrogen calories from glucose; electrolyte, utilizing nonnitrogen calories provided from a balanced casein diet and receiving an isovolemic infusion of electrolytes in the same composition as the TPN formula; 1/4 normal saline, also consuming the casein diet and receiving an isovolemic infusion of 1/4 normal saline; and an oral casein control (CON) without infusion. Results showed that there were no significant differences in tumor volume changes or tumor doubling time among the groups. However, tumor weight was significantly lower in groups receiving the TPN solution either orally or parenterally in comparison to the oral casein control. Pulmonary metastases were significantly lower in all parenteral groups, irrespective of solution composition, compared to the CON group. Thus it appears that parenteral fluid load rather than composition of the solution is the causative factor for the decrease in pulmonary metastases. PMID- 3108582 TI - Donor-specific antigen and cyclosporine in rat islet allografts. AB - Combination therapy with one dose of 3 M KCl extracted donor-soluble antigen (Ag) and a short course of cyclosporine (CsA) has proven to prolong the survival of kidney allografts by enhancing specific T-suppressor populations. This regimen is tested in rat islet allografts in this study (Lewis to ACI). A 3-day perioperative course of 10 mg/kg/day CsA on Days -1, 0, and 1 did not prolong graft survival (MST = 10.7 +/- 2.5 days vs 9.4 +/- 1.2 days in controls). When this course of CsA therapy was combined with a single dose of donor antigen on Day -1, the survival time was prolonged slightly but significantly (MST = 14.0 +/ 5.8 days). Three cycles of a 3-day course of CsA therapy at 7-day intervals, a total of nine doses of 10 mg/kg/day CsA, were effective in delaying rejection of islet allografts (MST = 26.4 +/- 30.3). Moreover, combined therapy with donor antigen and three cycles of a 3-day course of CsA prolonged the survival of islet allografts (MST = 57.7 +/- 51.4 days) with 50% of recipients still normoglycemic at 60 days after transplantation. These findings indicate that the combination therapy of donor antigen with a short course of CsA has a powerful effect to prevent the rejection of islet allografts, as shown in kidney allografts, in rats. PMID- 3108583 TI - Effects of enteral vs parenteral nutrition on reticuloendothelial function. AB - Previous investigations have shown that animals maintained with enteral nutrition are better able to survive an intraperitoneal bacterial challenge than animals receiving parenteral nutrition. The aim of this study was to assess the effects of enteral and parenteral nutrition on reticuloendothelial function. Eighteen enteral-fed male Sprague-Dawley rats had access to a standard hyperalimentation solution via a sipper tube ad libitum. Seventeen parenteral-fed animals received the same solution at an infusion rate determined by the volume ingested by the pair-fed enteral animals. All animals had central venous catheters. After 12 days, reticuloendothelial function was assessed by measuring the clearance rate (K) and the organ distribution of intravenous 51Cr-labeled sheep red blood cells and by plasma fibronectin levels. Nutritional status was assessed by body weight and nitrogen balance. K values in enteral and parenteral animals were similar (0.110 +/- 0.011 and 0.140 +/- 0.012, respectively, mean +/- SEM) as were plasma fibronectin levels (196 +/- 22 and 228 +/- 15 micrograms, respectively). Organ distribution of the 51Cr-labeled sheep red blood cells was the same in both groups. Nitrogen balance and body weights were also similar in both groups. These data demonstrate that in this experimental model enteral nutrition and parenteral nutrition were equally effective at maintaining reticuloendothelial function and nutritional status. PMID- 3108584 TI - Mannitol intoxication. PMID- 3108585 TI - The effects of neonatal androgenization of male rats on testosterone metabolism by the hypothalamus-pituitary-gonadal axis. AB - Male rats were androgenized on the third postnatal day by a single injection of 1 mg testosterone propionate. The in vitro metabolism of [4-14C]testosterone by pituitary and hypothalamus homogenates was investigated at the age of 90 days. The pituitary and hypothalamus homogenates from control and neonatally androgenized animals converted [4-14C]testosterone to the same metabolites, mainly 5 alpha-reduced derivatives; the quantitative yield of 5 alpha-reduced metabolites was much higher in the pituitary homogenates of androgenized rats. The hypothalamic homogenates showed no differences. In the androgenized rats a very significant increase of the plasma FSH levels was measured while the LH levels were also augmented. The plasma levels of testosterone were not different from the values in control rats, notwithstanding a 25% reduction in testes weight. The present experiments appear to indicate that the neonatal androgenization results in an accentuation of the sexual dimorphism which normally exists in the pituitary of adult rats for the 5 alpha-reductase activity. PMID- 3108586 TI - Hydroxyurea plus pelvic radiation versus placebo plus pelvic radiation in surgically staged stage IIIB cervical cancer. AB - Forty-five evaluable patients with stage IIIB carcinoma of the uterine cervix were entered into a prospective, double-blind, randomized study to evaluate the possible radiation-potentiating properties of hydroxyurea. All patients were documented to be without para-aortic lymph node metastasis by pretherapy staging para-aortic lymphadenectomy. The original plan of therapy was for continuous therapy (200 rads/day) of 6,000 rads of pelvic radiation for 6 weeks plus intrauterine radium. However, 16 patients received 6,000 rads in 8 weeks by split course therapy (2-week rest after 3,000 rads) plus radium. Twenty-nine patients received the planned continuous therapy. The median dose of pelvic radiation for patients who received continuous therapy or split-course radiation was 6,000 rads. Leukopenia (WBC less than 2,500/mm3) was significantly increased in the patients given hydroxyurea as compared to those given placebo (P less than .001). There was no statistically significant difference relative to anemia, thrombocytopenia, radiation skin reaction, diarrhea, or radiation-induced complications requiring surgical correction. The estimated 5-year progression free survival rate for the combined, continuous, and split-course radiation therapy hydroxyurea patients was 60%, and its was 52% for the corresponding placebo patients (P = .49). However, the estimated 5-year progression free survival rate for the correctly treated patients (continuous therapy) was 91% for the hydroxyurea group and 60% for the placebo group (P less than .06). PMID- 3108587 TI - Nodular liver lesions associated with chronic home hyperalimentation after massive enterectomy for ileal carcinoma. AB - A case of an ileal carcinoma involving the entire midgut treated with a massive enterectomy of the small bowel distal to the ligament of Treitz, the right colon, and part of the transverse colon is discussed. After 1 year on home hyperalimentation, hepatic nodules were seen on CT scans; metastases could not be proven. At 3 years a hepatic wedge resection was performed, multiple areas of necrosis and fibrosis were found, but no carcinoma. This case is presented as an example of an alternative in treatment for this type of carcinoma and to illustrate the problems of differential diagnosis of liver defects on the CT scan in patients on longterm hyperalimentation. PMID- 3108588 TI - Blood interactions in extracorporeal circulation: tests to evaluate the activation of proteins and formed blood elements. PMID- 3108589 TI - Autocrine stimulation of TNF-alpha mRNA expression in HL-60 cells. AB - We have employed a human promyelocytic leukemic cell line, HL-60, to investigate the conditions that regulate TNF-alpha gene expression in vitro. Using a cloned TNF-alpha specific cDNA probe, we show by Northern blot analysis that TNF-alpha mRNA rapidly accumulates in HL-60 cells following treatment with phorbol myristate acetate (PMA). TNF-alpha mRNA levels peak at 1-2 hours and then decline to base-line levels within 8 hours. TNF-alpha protein levels as detected in the supernatants of PMA-stimulated HL-60 cells peak at 2 hours and decline within 24 hours. Cytokines of recombinant source like interferon-alpha and -gamma, and, more intruigingly, TNF-beta as well as TNF-alpha itself are also able to induce transient TNF-alpha mRNA expression in HL-60 cells. In the presence of a protein kinase inhibitor, neither PMA nor any of the cytokines used are able to induce TNF-alpha mRNA accumulation, indicating that protein kinases may be crucially involved in signal transduction leading to activation of the TNF-alpha gene. The data presented provide new insights into the control of TNF-alpha gene expression suggesting regulatory functions of T- and B-cell derived lymphokines as well as a TNF-alpha-mediated positive feedback mechanism. PMID- 3108590 TI - Electromechanical effects of tetraethylammonium and K+ on histamine-induced contraction in pig isolated tracheal smooth muscle. AB - The effect of tetraethylammonium (TEA) and K+ on contractions to histamine and acetylcholine have been compared in the pig isolated trachea using organ bath and sucrose-gap techniques. Histamine elicited weak contractions, compared with acetylcholine; however, these contractions were markedly potentiated by pretreatment with TEA (10 mM) or by raising the external KCl concentration to 30 50 mM. Neither TEA nor K+ increased the sustained depolarization evoked by histamine (or acetylcholine) although oscillatory depolarizations were often observed in the presence of TEA. Verapamil and a zero Ca2+ Krebs solution reduced contractions to histamine and reduced or abolished the effect of TEA and K+ on histamine-induced contractions. The results unmask different mechanisms of contraction for histamine and acetylcholine. Histamine-induced tone appears to be linked with mechanisms sensitive to TEA and high K+, possibly involving increased translocation of Ca2+ across the plasma membrane. PMID- 3108591 TI - Isolation, biochemical characterization, and culture of lung type II cells of the rat. AB - A method is described for the isolation of rat lung epithelial Type II cells using trypsin digestion of tissue to release cells for subsequent separation by Percoll gradient centrifugation. Both the concentration of trypsin and the age (body weight) of the rat affect the yield from primary digestion and the final number of Type II cells obtained. A lung weighing 1 g from a 200 g rat yields approximately 30 X 10(6) washed Type II cells (approximately 25% of the total estimated lung population). These cells have a plating efficiency of 40-50% after 48 h of culture. The cells have a high alkaline to acid phosphatase ratio (usually greater than 4.0) compared with that of alveolar macrophages (0.1) and accumulate putrescine by an active transport mechanism with an apparent KM between 8 and 14 microM. Together with studies of [3H]thymidine uptake into DNA, which is maximal between 48 and 72 h of culture, these quantitative measurements form a good basis for investigating the interactions between a number of chemical agents and Type II cells in vitro. PMID- 3108592 TI - Immunogenetic factors as determinants of asbestosis. AB - To evaluate the possible role of immunogenetic factors as predisposing determinants of the development of asbestosis in exposed workers, we obtained 53 phenotypes of the human leucocyte antigen (HLA)-A, B, C, and DR antigens in 72 long-term workers of the mines and mills of Quebec and in a reference population of 150 residents. Among the asbestos workers, 32 did not have any abnormality and 40 had asbestosis. The 2 groups did not differ in term of age, exposure, or cigarette smoking habits. In agreement with previous reports, we found no significant change in frequency of the HLA-A, B, or C phenotypes. Furthermore, we did not find any significant change in the frequency of 10 phenotypes of the HLA DR loci. We conclude that immunogenetic factors are not major predisposing determinants of asbestosis. PMID- 3108593 TI - Systemic necrotizing angiitis with asthma: causes and precipitating factors in 43 cases. AB - Causes and precipitating factors for systemic necrotizing angiitis (NA) with asthma were sought in 43 patients, focusing on a history of vaccination and desensitization. Mean age of patients was 43.2 years. Diagnosis was based on histopathologic findings in 25 patients, arteriography in 2, and clinical criteria in 16. History of allergic manifestations (asthma, rhinitis, eczema, urticaria) was present in the family of 19 patients. Forty-two patients presented with asthma before development of NA and 23 of them were treated with steroids. Nineteen subjects gave a history of desensitization and 5 of vaccination in the 4 weeks preceding the disease. The main symptoms of NA were asthma in 43, fever in 25, weight loss in 31, peripheral neuropathy in 29, cutaneous signs in 25, digestive signs in 16 (abdominal pain, digestive bleeding, bowel perforation), noninfectious pneumopathy with pulmonary infiltrates in 33. Eosinophilia was 8,212 +/- 6,214/mm3. Antigen HBs was found in 2 of 30 patients. Prognosis of NA with asthma was good in 15 patients who recovered completely from the disease. Seven patients died and the other patients improved but remained under treatment. The survival curve showed that 75% of patients were alive after 60 months. Our findings suggest that different causes can be considered responsible for NA, and that, in cases of NA with asthma, there is reason to consider vaccination and desensitization as precipitating factors. PMID- 3108595 TI - [Gonococci producing beta-lactamase]. PMID- 3108594 TI - Subpopulations of T cells in lung biopsies from patients with pigeon breeder's disease. AB - Monoclonal antibodies were used to determine surface phenotypes of T cells in tissue obtained by open lung biopsies from patients with chronic hypersensitivity pneumonitis (pigeon breeder's disease). The results indicate that an increased number of suppressor/cytotoxic cells is present in these patients when compared with the number of helper/inducer cells. These findings, which were present within the interstitium, are consistent with those found in bronchoalveolar lavage of patients with this disease. In addition, in two-thirds of the patients there was a greater total number of helper and suppressor cells than the total count for Pan T cells. A possible interpretation of these findings might be the presence of both markers in the same cell. PMID- 3108596 TI - [Gonococci producing beta-lactamase in male urethritis]. PMID- 3108597 TI - [Correlation of the resistance to disinfectants and the hemeprotein level in Pseudomonas aeruginosa strains]. PMID- 3108598 TI - Effect of L-threo-3,4-dihydroxyphenylserine(L-threo-DOPS) on brain and serum MHPG levels in mice: evidence for NE formation in CNS. AB - Effects of L-threo-DOPS on brain and serum concentrations of 3-methoxy-4 hydroxyphenylethyleneglycol (MHPG), a major metabolite of 1-norepinephrine(NE) were studied in mice. An intraperitoneal(i.p.) injection of L-threo-DOPS markedly increased both serum and brain MHPG levels in mice. This increase in the brain was dose-dependent at doses up to 800 mg/kg, and lasted for 4 h or more. Though the increase in serum total-MHPG was 3-4 times greater than that in brain MHPG, the decline was rapid as compared with the case of brain MHPG. The L-threo-DOPS induced increase in MHPG was inhibited by i.p. pretreatment with benserazide, a peripheral decarboxylase inhibitor, in both serum and brain. This inhibition in the brain, however, was observed at about 20 times higher doses of benserazide than that in serum. On the contrary, an intracerebroventricular(i.c.v.) injection of benserazide inhibited the increase in brain MHPG to about the same degree as that in serum MHPG. These results suggest that the L-threo-DOPS-induced increase in brain MHPG is not likely to originate in peripheral organs including the brain capillary, and that L-threo-DOPS can be converted to NE by aromatic L-amino acid decarboxylase(AADC) in the brain parenchyma. PMID- 3108599 TI - Night-day differences in the ultradian rhythmicity of plasma renin activity. AB - During night-sleep, plasma renin activity displays periodic oscillations which are closely related to the alternation of REM-NREM sleep. To see whether this nocturnal rhythm persisted during the day-time, plasma renin activity was measured every 10 min for 24 hours in 4 human volunteers and in 4 others over a 10-h day-time period. To avoid the influence of repeated food intake which stimulates renin release, the subjects were on continuous enteral nutrition. Spectral analyses of the data revealed clear differences between the nocturnal and the diurnal PRA patterns. In subjects on enteral nutrition, sustained 100-min oscillations with strong spectral densities persisted during the night. They were closely related to REM-NREM cycles. During the day-time, however, the fluctuations were damped and less regular, and power spectra were split into 2 or 3 peaks without any predominant period. These results demonstrate that regular 100-min PRA oscillations could only be detected during night-sleep. The clear night-day differences suggest that the underlying oscillatory mechanisms may be weaker during day-time or may be counteracted by other physiological processes. PMID- 3108600 TI - In vivo and in vitro effect of naloxone on prolactin response to TRH in rat. AB - In adult male Wistar rats submitted to a standardized noise stress, intravenous TRH induced a prolactin (PRL) secretory response. Prior IV naloxone administration not only lowered plasma PRL levels in those stressed rats but abolished also the stimulatory action of TRH. This effect was further studied by superfusion experiments on enriched PRL cell suspensions (70% lactotrophs) from female adult Wistar rats. Naloxone kept unaffected the basal PRL secretion but lowered significantly that induced by TRH. These experiments suggest a dual effect of naloxone on rat PRL secretion, one exerted on central opioid receptors lowering stress-related increased basal PRL levels, the other inhibiting the TRH dependent PRL secretion exerted at the lactotroph level itself. PMID- 3108601 TI - Priorities for adolescent health: recommendations of a national conference. PMID- 3108602 TI - Prostaglandin F2 alpha for treating severe postpartum hemorrhage. PMID- 3108603 TI - Patient teaching: answering reader inquiries. PMID- 3108604 TI - Erythropoiesis and neonatal blood transfusions. PMID- 3108605 TI - How to administer blood components to children. PMID- 3108606 TI - Making the transition to mother-baby care. PMID- 3108607 TI - Self-administered medications for obstetric patients. PMID- 3108608 TI - Establishing and evaluating a children's sick room program. PMID- 3108609 TI - Obtaining consent to treat minors. PMID- 3108610 TI - Readying research for practice. PMID- 3108611 TI - [Whole-body radiometric study of protein and lipid metabolism in thyroid pathology]. AB - Radiometry of the whole body and its organs was employed to study certain aspects of protein-aminoacid and lipid metabolism in patients with thyroid diseases. Metabolism of human serum 131I-albumin was studied in 12 patients with neurocirculatory dystonia (as a premorbid stage of toxic goiter), in 13 patients with diffuse toxic goiter (in 10 before and after drug therapy) and in 9 controls. 75Se-methionine aminoacid metabolism was investigated in 9 patients with toxic thyroid adenoma and in 13 controls. The body cell mass was determined in 82 patients with thyrotoxicosis by a measurable amount of 40K. These data were compared with those of 249 healthy persons. The assimilation of 131I-oleic acid in the G. I. tract was determined in 6 patients with neurocirculatory dystonia, in 18 patients with thyrotoxicosis (in 5 before and after drug therapy) and in 12 controls. The assimilation of 131I-glycerol trioleate was determined in 6 patients with neurocirculatory dystonia, in 16 patients with thyrotoxicosis (in 3 before and after therapy), in 3 patients with primary hypothyroidism and in 10 controls. An increase in catabolism of labeled albumin, intensification of labeled methionine metabolism at the tissue level, signs of a decrease in the total amount of metabolic albumin in the body were revealed. Intensification of protein metabolism resulted in a decrease in the body cell mass of these patients. After adequate therapy the above indices of protein metabolism in patients with thyrotoxicosis returned to normal. The assimilation of fatty acids and neutral fat was disturbed both in thyrotoxicosis and hypothyroidism. PMID- 3108612 TI - [Potentiometric method of analyzing CO2 transfer in a blood membrane oxygenator]. AB - The paper proposes a method of the CO2 transfer intensity analysis in membrane oxygenators of the "MOCT" type. The dependence of the CO2 elimination rate on the liquid flow and oxygen blow-down rates for various oxygenators have been studied on a closed loop circuit. It has been established that the elimination rate depends not only on the transfer through membrane and the liquid layer, but also on the CO2 hydration-dehydration rate. PMID- 3108613 TI - [Nutritional status of the children of the village of Bobo-Dioulasso and a rural zone of West Burkinabe]. AB - Nutritional status of children aged 9 months-4 years has been studied by measuring the brachial perimeter in a sample of Bobo-Dioulasso and a neighbouring village populations. Nutritional deficiency affected 45% of the age group 9 months-23 months and 17% of the age group 2 years-4 years. Results were similar in both urban and rural areas. PMID- 3108614 TI - [A case of ureteral bilharziasis followed for 22 years]. AB - The authors report on one case of urinary schistosomiasis monitored for 22 years. It illustrated the problems posed by the "bilharzial uretero-hydronephrosis". They analyse the different therapy problems which have to have been successively solved: Low double ureteral stenosis. The difficulty to be certain of such a stenosis is recalled. The possibility of a reflux or an ureteral atony must be eliminated. True stenosis must be operated without delay; Kidney cancer revealed 20 years later through chronic renal failure by vesico-ureteric reflux caused by the first surgical intervention (latero-lateral vesico-ureteric anastomosis); Iatrogenic vesico-ureteral reflux, treated by uretero-vesical implantation on "psoic" bladder with anti-reflux submucous path. The future of such a chronic renal failure is linked to the capability of the remaining ureter to ensure an acceptable passage of urine, and to the rehabilitation possibility of the kidney. Finally, the authors recalled the difficult therapeutic indications in case of ureteral attack due to bilharziosis. PMID- 3108615 TI - Noninvasive evaluation of effects of an aldose reductase inhibitor in rat brain by 19F FDG NMR spectroscopy. AB - The inhibitory effects of an aldose reductase inhibitor, sorbinil (Pfizer, NY), on cerebral glucose metabolism were investigated noninvasively in rat brain using 19F nuclear magnetic resonance (NMR) spectroscopy and 2-fluoro-2-deoxy-D-glucose (2-FDG). Sorbinil given orally in the daily recommended doses (25 mg/kg) for man for the treatment of diabetic complications inhibited 2-FDG flux into the aldose reductase sorbitol (ARS) pathway, demonstrated as a reduction in the intensity of the ARS index resonance as well as an increase in the resonance area ratio between the pentose monophosphate shunt (PMS) and ARS index resonances (PMS/ARS ratio). Spatial metabolite mapping using rotating frame one-dimensional zeugmatography indicated that the inhibitory effect is spatially nonspecific. The present study is the first direct noninvasive observation of the effects of a pharmacological agent on cerebral enzymatic activities. PMID- 3108616 TI - [Simultaneous determination of specific antigen, antibody and immune complexes in the serum of patients with chronic schistosomiasis]. AB - The main steps of a sensitive and quantitative technique for the simultaneous determination, in the same microplate, of antigen, antibody and specific immune complexes has been described. The assay involved principles of the double sandwich technique used in the "Enzyme-Linked Immunosorbent Assay" (ELISA). The technique proved to be useful for the estimation of antigen, antibody and specific immune complexes in sera of patients with human chronic hepato intestinal schistosomiasis. PMID- 3108617 TI - [Influence of BCG in the control of humoral deficiency induced by mastocytoma p 815]. AB - Viable BCG bacilli, in a lipid emulsion, inoculated intravenously, were capable of reverting the profound humoral immunosuppression induced in adult DBA/2 mice by the mastocytoma P-815. BCG increased not only the number of hemolytic plaque forming cells, but also the serum titers of hemagglutinating IgM antibodies. However, no blocking effect was detected on normal tumor progression. PMID- 3108619 TI - Research activities of the Scientific Working Group (SWG) on Chagas' disease 1982 1985. Report of the Steering Committees (SC) to the Scientific and Technical Review Committee (STRC). PMID- 3108618 TI - Differential effect of culture epimastigotes and blood-form trypomastigotes on normal mouse splenocyte responsiveness to mitogens. AB - Blood form trypomastigotes of the Y strain of T. cruzi, produced a strong inhibition of the blastogenic response to T and B cell mitogens, of the C3H/He, C57BL/6 and BALB/cJ strains of mice, while culture epimastigotes of the Y strain kept in a medium that allows parasite growth at 26 degrees, 30 degrees, 34 degrees and 37 degrees C produced a strong stimulatory effect that was even higher than the effect of the mitogens alone. Both the inhibitory or the stimulatory effects were dose-dependent. The stimulatory effect of epimastigotes was also temperature-dependent producing increased stimulation indexes as the temperature of parasite cultures was raised. Metabolically active, living parasites seemed to be necessary for an improved lymphocyte stimulation suggesting a potential role of secreted metabolites as polyclonal activators of mouse lymphocytes. PMID- 3108620 TI - [13th annual meeting on basic research in Chagas' disease. Caxambu, Minas Gerais, Brazil, 10-12 November 1986. Abstracts]. PMID- 3108621 TI - Metabolism of D- and DL-beta-hydroxybutyrate by mouse embryos in vitro. AB - Rates of 14CO2 production by mouse conceptuses in vitro from D- and DL-[3-14C] beta-hydroxybutyrate (beta OHB) were determined during the period of organogenesis (days 9 through 12 of gestation) in the presence of 4 to 32 mmol/L DL-beta OHB. During this time period the rates 14CO2 production from D-beta OHB metabolism are concentration-dependent, increase on each day of gestation, and the site of metabolism appears to shift from the visceral yolk sac placenta to the embryo proper. In contrast to fetal and neonatal tissues, the rates of 14CO2 production from DL-beta OHB oxidation is significantly greater than from D-beta OHB suggesting that the utilization of the L-isomer may be equal to or greater than that of the D-form. PMID- 3108622 TI - Bioenergetic and metabolic response to continuous v intermittent nasoenteric feeding. AB - Resting thermal energy losses and metabolic balances of N, K, P, Ca, Na, and Mg were compared during continuous and intermittent nasoenteric formula infusion in four healthy men. Each feeding protocol lasted 1 week in a 4-week double crossover experiment. The initial feeding schedule was established randomly. Continuous nasoenteric formula infusion produced no increase in thermal energy losses above the fasting level; energy expenditure fell with sleep to the same extent as with intermittent feeding. Thermal losses were similar during intermittent feeding with the exception of the thermic effect of food that produced an additional average energy loss of 115.7 kcal/d. The total resting and sleeping 24-hour energy expenditure was significantly lower (P less than .01) during continuous formula infusion (means +/- SD for n = 8 balance periods, 1344 +/- 119 kcal) compared to intermittent feeding (1457 +/- 179 kcal). No significant differences in nutrient absorption or balances of N, Na, Ca, and Mg were detected between the two feeding protocols. In contrast, continuous infusion of formula was accompanied by negative balances of K and the cytosolic portion of P; weight balance was slightly negative. Weight, K, and cytosolic P balances were all positive during intermittent feeding (P = NS, less than 0.01, and P less than .05 compared to respective continuous infusion periods). Hence, 1 week of continuous nasogastric formula infusion is associated with similar nutrient absorption, a significant reduction in thermal energy losses, and equivalent protein (N) balance relative to intermittent feeding. Differences in weight balance between the two feeding protocols can be ascribed largely to fluid and mineral shifts. These results suggest that energy requirements are lower during continuous formula infusion by about 100 kcal/d compared to regular meal ingestion. PMID- 3108623 TI - Acute effects of ingestion of carbohydrate, protein, or fat on cardiac glycogen metabolism in rats. AB - Administration of large doses of insulin to intact rats has been shown to stimulate cardiac glycogen synthase phosphatase activity. This results in an activation of glycogen synthase. However, whether a more physiologic stimulus for insulin secretion also resulted in activation of synthase had not been studied. In the present study, rats were fed glucose, casein hydrolysate, or a mixed meal after a 24-hour fast as a means of physiologically stimulating insulin secretion. Lard was fed as a noninsulinotropic nutrient for comparative purposes. Plasma insulin was significantly increased by 15 minutes in rats given a mixed meal or glucose, but surprisingly, no change was observed in rats fed casein hydrolysate. As expected, no change in plasma insulin was observed in rats fed lard. Synthase phosphatase activity was stimulated in rats fed a mixed meal, glucose, or casein hydrolysate, but not in rats fed lard. Likewise, the proportion of synthase in the active (I) form was significantly increased in rats fed a mixed meal, glucose, or casein hydrolysate, but not in rats fed lard. The increase in phosphatase activity and the increased proportion of synthase in the active form following ingestion of casein hydrolysate was unexpected since this occurred in the absence of an increase in insulin. The proportion of phosphorylase in the active (a) form decreased in rats fed glucose, but remained unchanged in rats fed a mixed meal, casein hydrolysate, or lard. The cardiac glycogen concentration decreased dramatically in rats fed casein hydrolysate. Following the other meals, there was either no change or the decrease was modest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108624 TI - Isolation, localization, and properties of the oncodevelopmental calcium-binding protein oncomodulin. PMID- 3108625 TI - Cloning of the gene for protein S: a development-specific Ca2+-binding protein from Myxococcus xanthus. PMID- 3108626 TI - Rat calbindin D28K: purification, quantitation, immunocytochemical localization, and comparative aspects. PMID- 3108627 TI - Separate regulatory systems for the repression of metE and btuB by vitamin B12 in Escherichia coli. AB - Synthesis of the btuB-encoded outer membrane receptor for vitamin B12 and the metE-encoded homocysteine methyltransferase is repressed by growth of Escherichia coli in the presence of vitamin B12. The regulation by vitamin B12 of the production of beta-galactosidase in strains carrying btuB-lac or metE-lac operon fusions indicated that repression of both genes operates at the transcriptional level. Selection for expression of these fusions under repressive conditions allowed isolation of second-site mutations in which repressibility by vitamin B12 had been lost. Mutations in metH and metF prevented vitamin B12-dependent regulation of metE, but not that of btuB. Mutations in btuB and other genes involved in uptake of the vitamin eliminated or reduced repression. Mutations in the newly identified gene, btuR, controlled the repressibility of btuB, but had no effect on metE regulation. The btuR gene resides at 27.9 min on the genetic map in the gene order cysB-topA-btuR-trp; it acts in a trans-dominant manner and appears to encode a repressor of btuB transcription. PMID- 3108628 TI - Klebsiella pneumoniae nif-lac fusions are expressed in Agrobacterium tumefaciens C58. AB - Plasmids containing hybrid genes, in which different Klebsiella pneumoniae nif (nitrogen-fixation) promoters were fused with the structural part of the Escherichia coli lac operon, were introduced into a double auxotrophic derivative of Agrobacterium tumefaciens C58. A study of their expression in the new host was made simple by the inherent inability of A. tumefaciens C58 to produce beta galactosidase unless provided with the wild-type lac operon of E. coli. As shown by quantitative measurements of the enzyme, all K. pneumoniae promoters were expressed well in A. tumefaciens C58, even under conditions known to repress them. It also has been shown that the activity of K. pneumoniae nif A is essential for the expression of nifHDK even when introduced into A. tumefaciens. After entering the new host the plasmids, the nif genes and the fusion alleles contained in them, remained stable. Possible mechanisms responsible for the constitutive behaviour of nif promoters in A. tumefaciens are discussed. PMID- 3108629 TI - Induction, purification and some properties of phage tail-like particles from Myxococcus coralloides D. AB - Myxococcus coralloides D was lysogenic for a defective prophage. The particles of the defective bacteriophage could be induced by ultraviolet light and mitomycin C, but the particles did not appear in the supernatants, unless the cells were lysed with chloroform. The phage tails were purified by using a two-phase separation method, ultracentrifugation, chromatography through Sepharose 4B, treatment with chloroform, dialysis and centrifugation on a sucrose gradient. The chemical analysis of the purified samples revealed that the phage tails contained only proteins, neither DNA nor RNA. The different parts of the phage tails (sheath, core and baseplate) did not have the same sensitivity to the chemical and physical agents which were assayed. PMID- 3108630 TI - Characterization of intracellular deoxyribonucleases of Bacillus subtilis by SDS polyacrylamide gel electrophoresis. AB - Electrophoresis in polyacrylamide gels containing DNA was used to study nucleolytic activities in Bacillus. Optimal conditions (cations, pH and substrate) and a general pattern of DNases of B. subtilis 168 were established, revealing the presence of twelve to fourteen defined bands with DNase activity. Fractionation of cell cultures showed that most of the nucleases were located in the bacterial cytosol, and only two activities were membrane-associated. The employment of plasmid DNA in the gels facilitated distinguishing between exo- and endonucleases, the latter being the most active bands. The DNase pattern of various strains of B. subtilis, and species of the genus Bacillus, was compared. Evident differences were observed although similarities exist. PMID- 3108631 TI - Comparative antigenicity of spore coat proteins from Bacillus species using antibody to spore coat proteins of Bacillus megaterium. AB - Spore coat proteins obtained by extraction with sodium dodecylsulfate/dithiothreitol from six Bacillus spores were compared by immunoblot analysis using antibodies to spore coat proteins from two strains of B. megaterium. Although the extract from spores of each strain had heterogenous proteins with various molecular weights, there were some bands which cross reacted with specific antibodies from B. megaterium spores. Specific antibody to 48K protein from B. megaterium ATCC 12872 cross-reacted with 17K protein from B. megaterium ATCC 19213, 13K protein from B. cereus and 50K protein from B. subtilis 60015 and B. subtilis NRRL B558. Also, specific antibody to 22K protein from the same strain cross-reacted with 22K and 17K proteins from B. megaterium ATCC 19213 and 13K protein from B. cereus T. Specific antibody to 17K protein from B. megaterium ATCC 19213 reacted with 22K and 19K proteins in addition to 17K protein of own strain, and it was cross-reactive with 16K protein from B. megaterium ATCC 12872, 19K and 27K proteins from B. thiaminolyticus, 13K protein from B. cereus. PMID- 3108632 TI - Inhibitory action of dipicolinic acid on the activation of inactive glucose dehydrogenase from Bacillus subtilis spores. PMID- 3108633 TI - [Characteristics of the fatty acid composition of Pseudomonas aeruginosa cells with different degrees of resistance to dodecyl sulfate]. AB - The fatty acid composition of Pseudomonas aeruginosa 1C destroying anionic surfactant alkyl sulfates was studied after its cultivation under different conditions which caused different resistance of the cells against sodium dodecyl sulfate (SDS). The content of monounsaturated fatty acids (in particular, octadecenoic acid) increased while the content of cyclopropane fatty acids decreased in cells resistant against SDS. PMID- 3108634 TI - Rheumatoid arthritis: a disturbance in copper homeostasis. AB - That understanding the mode of action of antirheumatic drugs could help understand the etiology of rheumatoid arthritis is complicated by their apparent different actions on different target cells. The point of view adopted here is that the primary defect in rheumatoid arthritis will be similarly altered by such drugs. The common reactivity of two of the most widely prescribed drugs, D penicillamine and sodium aurothiomalate, toward albumin-bound copper is proposed as their primary site of action. Elevated serum concentration of this form of copper has previously been suggested to perturb synovial cell metabolism and trigger the disease. PMID- 3108635 TI - Agents causing non-A non-B hepatitis: could one be a prion? AB - Non-A non-B hepatitis is caused by an unknown infectious agent or agents, and can be transmitted by blood or products derived from blood. Laboratory and clinical data demonstrate that procedures which inactivate the AIDS virus are not sufficient to prevent non-A non-B hepatitis transmission. The possibility is suggested that at least one of the putative non-A non-B hepatitis agents might be a unique infectious agent such as a prion. PMID- 3108636 TI - Endogenous gamma interferon production may protect against hepatic cirrhosis and administration of exogenous gamma interferon may protect individuals prone to cirrhosis. AB - Hepatic cirrhosis is characterized by the replacement of normal liver parenchyma by collagenous fibrous tissue. Although hepatocytes in the adult retain the ability to divide, under certain circumstances hepatocyte death leads to replacement with fibroblasts and collagen. Whether a particular form of hepatocyte injury leads to cirrhosis is dependent upon the stimulus for the injury and is also highly variable between individuals. It has recently been shown that gamma interferon inhibits collagen synthesis in vitro and fibrosis in vivo. I suggest that individuals who are prone to hepatic cirrhosis from a given stimulus are low producers of gamma interferon while high gamma interferon producers are relatively protected from cirrhosis. I also hypothesize that exogenous gamma interferon administration may halt or slow the progression of cirrhosis in patients with early progressive cirrhosis. Alternatively, endogenous gamma interferon production could be stimulated in these patients with progressive cirrhosis. One agent which may be useful for inducing endogenous gamma interferon is GE-132, an organogermanium. PMID- 3108637 TI - Alfentanil. PMID- 3108638 TI - Treatment of lymphohistiocytic erythrophagocytosis with VP-16 and aziridinylbenzoquinone. AB - Lymphohistiocytic erythrophagocytosis (LE) is a usually fatal disease characterized by fever, organomegaly, hyperlipidemia, central nervous system involvement, and cellular immunodeficiency. Treatment with corticosteroids, cytotoxic chemotherapy, and blood exchange is unsuccessful. We have treated two children with the epipodophyllotoxin VP-16 and with intrathecal chemotherapy. Each patient had an initial complete response, and one remains in remission 36 months after therapy began. Aziridinylbenzoquinone (AZQ) therapy induced a complete response in a patient who relapsed during VP-16 therapy. A combination of VP-16 and intrathecal chemotherapy appears to be the most effective therapy for LE, and further evaluation of the role of AZQ is indicated. PMID- 3108639 TI - [Norplant--a subdermal contraceptive implant]. PMID- 3108640 TI - Static multileaf collimator for fast-neutron therapy. AB - This paper describes a multileaf collimator, designed to obtain irregularly shaped neutron fields, that fits into an existing fixed field-size collimator system. The shape of the desired portal field is obtained by appropriately setting the position of each leaf of the collimator. The collimator consists of 40 polyethylene leaves to produce fields of irregular shape of up to 400 cm2. The leaves are interlaced with grooves to prevent neutron leakage. The measured penumbra defined by the multileaf collimator is similar to that defined by the same length fixed field-size water extended polyester (WEP) collimator. The multileaf collimator has a lower neutron transmission due to its higher hydrogen concentration. PMID- 3108641 TI - [Behavior of arterial and venous blood gas in acute renal insufficiency caused by acute post-infectious glomerulonephritis. Considerations on the pathogenesis of nephritic edema in relation to microcirculatory and hemorheologic findings]. PMID- 3108642 TI - Endocrine profile in Noonan's syndrome. PMID- 3108643 TI - Assessment of the response to GH-releasing factor in children with essential obesity. PMID- 3108644 TI - Smokeless tobacco use in the United States--Behavioral Risk Factor Surveillance System, 1986. PMID- 3108645 TI - Investigation of a cluster of appendicitis cases--Texas. PMID- 3108646 TI - Indian Health Service facilities become smoke-free. PMID- 3108647 TI - Nutritional status of minority children--United States, 1986. PMID- 3108648 TI - Premature mortality due to congenital anomalies--United States, 1984. PMID- 3108649 TI - Prevention and control of influenza. PMID- 3108650 TI - Preliminary report: paralytic poliomyelitis--Senegal, 1986. PMID- 3108651 TI - Increases in primary and secondary syphilis--United States. PMID- 3108652 TI - Acanthamoeba keratitis in soft-contact-lens wearers. PMID- 3108653 TI - Cigarette smoking among blacks and other minority populations. PMID- 3108654 TI - [Selenium deficiency and cardiomyopathy in a patient on long-term parenteral nutrition]. AB - A 28 year-old Japanese male with Crohn's disease maintained on total parenteral nutrition for 5 consecutive years showed congestive cardiomyopathy. His symptoms (palpitation and precordial pain), arrhythmia on ECG and cardiomegaly on chest X ray film were progressive. By intravenous selenium supplementation of 100 micrograms/day (selenite) his symptoms disappeared dramatically and plasma selenium level, erythrocyte selenium level and glutathione peroxidase activity improved to normal ranges. It is suggested that this myocardial damage was caused by selenium deficiency. PMID- 3108655 TI - [Comparative study with reduction rate of tumor and decrease rate of tumor markers as an effect of MMC on human cancer producing CEA and CA19-9 xenotransplanted in nude mice]. PMID- 3108656 TI - Inhibition of ADP-ribosylation of histone H1 by analogs of diadenosine 5',5''' p1,p4-tetraphosphate. AB - The effects of analogs of diadenosine 5',5'''-p1,p4-tetraphosphate (Ap4A) were examined on the ADP-ribosylation reaction of histone H1 catalysed by purified bovine thymus poly(ADP-ribose)transferase. Among the compounds tested, epsilon Ap4A and ApCH2pppA were shown to be the most efficient inhibitors of the enzyme. From kinetic studies of their action, it appears that epsilon Ap4A and ApCH2pppA might be 'mixed type' inhibitors. PMID- 3108657 TI - [Intragastric long-term pH measurement for adjusting drug therapy of gastroduodenal ulcer hemorrhage in childhood]. AB - A constant gastric pH-value greater than 5 is decisive in drug therapy and prophylaxis of relapse after gastroduodenal ulcer bleeding. The optimal adjustment of therapy can be controlled by gastric long-time pH-metry. The method is demonstrated by representative case histories of children. PMID- 3108658 TI - Comparative study of the clastogenic efficiency of ethyl methanesulfonate and diethyl sulfate in Drosophila melanogaster mature sperm. AB - Chromosome loss and translocation tests were carried out in Drosophila melanogaster sperm, stored in untreated females for up to 24 days, to compare the clastogenicity of ethyl methanesulfonate (EMS) and diethyl sulfate (DES). The sex linked recessive lethal test was used as a "biological dosimeter" and the following results were obtained: The yield of 2-3 translocations induced by both mutagens increased steadily with storage, being significantly higher after EMS than after DES treatment. The frequencies of partial losses induced by EMS and DES were similar and increased with storage. With up to 11 days' storage, the frequency of complete loss induced by DES was higher than that induced by EMS and remained unchanged when storage was extended to 24 days. Complete loss induced by EMS increased significantly with further storage (12-24 days). With DES, complete (but not partial) loss was detected with a dose at which EMS failed to modify the control values. These data suggest that the lower recovery of II-III translocations after treatment with DES does not result from a low breaking capacity but from a diminished or delayed rejoining of the induced breaks. This could be due to a physiological impairment of the treated cells by the high toxicity of DES or to an actual lower rejoinability of the broken ends. The differential recovery of complete and partial losses after DES treatment further suggests that the mechanisms leading to the fixation of both types of damage are somehow different, and that processes intervening in the recovery of partial losses are less affected, or not at all, by the proposed reduced rejoining of chromosome breaks. PMID- 3108659 TI - Modifying role of dietary factors on the mutagenicity of aflatoxin B1: in vitro effect of vitamins. AB - 19 vitamins including some derivatives have been tested for their ability to suppress mutagenic activity of aflatoxin B1 (AFB1) towards Salmonella typhimurium strain TA100 activated with a rat-liver metabolic activation system. Several vitamins have shown an ability to inhibit the mutagenic potency of AFB1. The values of ID50, i.e. the dose required to inhibit mutagenic activity by 50% calculated from dose-response curves for each vitamin show retinoids, riboflavin, folic acid, menadione, cyanocobalamin, ascorbic acid and pyridoxine to be significantly antimutagenic. Although inhibition by vitamins is apparent over a range of AFB1 concentrations, their effect is more pronounced at lower concentrations of AFB1. When combined data are expressed in terms of specific mutagenicity, riboflavin, retinol and menadione have been found to possess exceptional inhibitory ability in as much as, on a molar basis, only 15-40-fold excess vitamins can inhibit the mutagenic potency of AFB1 by 50%. Their action is possibly mediated through interaction with microsomal activating enzymes. Previous evidence from this laboratory about their inhibitory action on DNA adduct formation and metabolic activation together with the present results suggest that certain vitamins notably retinoids and riboflavin may have potential anticarcinogenic activity against AFB1. PMID- 3108660 TI - Cytogenetic analysis in workers occupationally exposed to nickel carbonyl. AB - Chromosomal aberration and sister-chromatid exchange (SCE) base-line frequencies and SCE frequencies induced by 10 ng/ml mitomycin C (MMC) were analysed in cultured peripheral lymphocytes of 65 workers occupationally exposed to nickel carbonyl Ni(CO)4. The subjects were divided into 4 groups: (1) control; (2) exposed to nickel carbonyl (= exposed); (3) cigarette smokers; (4) smoking exposed. The results show that there are no significant differences in chromosomal aberration frequencies, breaks or gaps, between the various groups. However, the SCE base-line frequency of the smoking-exposed group, with an average of 7.7/cell, was significantly higher than that of the control group, with an average of 6.5/cell (P less than 0.01), and also than that of the exposed group with an average of 5.9/cell (P less than 0.01). Similarly, the SCE frequency induced by 10 ng/ml MMC in the smoking-exposed group which averaged 15.5/cell was significantly higher than that of the control group (average of 13.2/cell (P less than 0.05], and also than that of the exposed group with an average of 12.3/cell (P less than 0.01). Under our experimental conditions, it may be that the level of exposure was not high enough to elicit an increase in chromosomal aberrations and SCE frequencies in the non-smoker exposed group. The fact that an increase in SCE frequencies was only found in the smoking-exposed group implies that the two factors, smoking and exposure to nickel carbonyl, are jointly responsible for the result. PMID- 3108661 TI - Hepatocyte-mediated SCE induction by indirect mutagens: importance of hepatocyte density and cell-to-cell contact. AB - The SCE-inducing effects of the indirectly acting mutagens cyclophosphamide (CP), dimethylnitrosamine (DMN) and aflatoxin B1 (AFB1) were analysed in hepatocyte (hpc)/mammalian cell coculture systems with regard to the importance of the hpc density. V79 cells and human lymphocytes served as target cells. For all 3 compounds steadily increasing genetic effects were observed when the hpc density was increased from 3.2 X 10(4) up to 3.2 X 10(6) viable hpc per culture (25-cm2 flask), i.e. the more hpc available for metabolisation, the more genetic effects induced. The frequency distributions of the CP-induced SCE values were clearly different from those obtained with DMN, especially when high hpc densities were used: distribution patterns obtained for the mutagen with stable metabolites (CP) are characterized by the presence of distinct maxima and the absence of cells with SCE control values, whereas distribution patterns for the mutagen with very short-lived metabolites (DMN) can be described by the absence of maxima and the presence of cells with SCE control values. The frequency distributions of the AFB1-induced SCE values were more similar to the CP type than to the DMN type. From these results it is deduced that close contact between metabolising and target cells is necessary for the detection of the genotoxic effect of DMN. For CP and AFB1 a direct contact seems not to be essential, i.e. reactive intermediates may also be transported via the culture medium to the target cells. PMID- 3108663 TI - Nurses study problems faced by pregnant diabetics. PMID- 3108662 TI - Evaluation of the genetic and embryotoxic effects of bis(tri-n-butyltin)oxide (TBTO), a broad-spectrum pesticide, in multiple in vivo and in vitro short-term tests. AB - The genetic and embryotoxic effects of bis(tri-n-butyltin)oxide (TBTO) were evaluated in multiple in vivo and in vitro short-term tests preparatory to its potential wide use as a molluscicide in control of schistosomiasis. When tested in the rec assay in Bacillus subtilis, TBTO was not mutagenic and it did not induce reverse mutations in Klebsiella pneumoniae. Neither in the presence nor in the absecne of rat liver activation system did TBTO produce point mutations in Salmonella typhimurium strains TA1530, TA1535, TA1538, TA97, TA98 or TA100. TBTO was matagenic in strain TA100 in a fluctuation test, but only in the presence of rat liver S9 (Aroclor-induced). TBTO did not induce gene mutations in the yeast Schizosaccharomyces pombe, mitotic gene conversions in the yeast Saccharomyces cerevisiae, nor sister-chromatid exchange in Chinese hamster ovary cells in the presence or absence of rat or mouse liver S9. In the latter cells, structural chromosomal aberrations, endoreduplicated and polyploid cells were induced. TBTO did not induce gene mutations in V79 Chinese hamster cells (to 8-azaguanine-, ouabain- or 6-thioguanine-resistance) in the presence of a rat liver postmitochondrial fraction or in cell (hamster embryo cells and human and mouse epidermal keratinocyte)-mediated assays. In mouse lymphoma cells, TBTO did not induce 6-thioguanine- or BUdR-resistant mutations. As many tumour promoters inhibit metabolic cooperation between V79 Chinese hamster 6-thioguanine resistant/-sensitive cells, TBTO was tested but showed no such activity. TBTO was examined for the induction of recessive lethal mutations in adult Berlin K male Drosophila melanogaster, either by feeding or by injection. Doses of 0.37 or 0.74 mM did not increase the number of X-linked recessive lethal mutations. An increased number of micronuclei was observed in the polychromatic erythrocytes of male BALB/c mice 48 h after a single oral dose of TBTO (60 mg/kg bw), while a lower dose (30 mg/kg bw) was ineffective. Neither of the two doses had induced micronuclei 30 h after treatment. The reproductive toxicity of TBTO was studied in NMRI mice. In a 10-day toxicity study, the LD50 and LD10 were 74 and 34 mg/kg bw, respectively. An increased frequency of cleft palates was seen in the fetuses of mice (compared with controls, 0.7%) treated orally during pregnancy with 11.7 mg/kg TBTO (7%), 23.4 mg/kg (24%) or 35 mg/kg (48%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3108664 TI - Shattuck lecture--what is quality care? PMID- 3108665 TI - Insurance for long-term care. Some definitions, problems, and guidelines for action. PMID- 3108666 TI - Growth inhibition of pathogenic yeast isolates by alpha-difluoromethylornithine: an inhibition of ornithine decarboxylase. AB - A large body of evidence exists suggesting that polyamines can play essential roles in cellular growth and differentiation. We examined the ability of alpha difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, the major rate-limiting enzyme in polyamine biosynthesis, to inhibit the growth of Candida albicans, C. tropicalis, and C. parapsilosis. Substantial growth-inhibition was observed for all three species at DFMO concentrations ranging from 1 to 100 mM. C. tropicalis was significantly more susceptible to DFMO than C. albicans or C. parapsilosis. Depletion of cellular polyamine pools was seen in all 3 species following exposure to DFMO and polyamine depletion enhanced the susceptibility of the organisms to DFMO. The action of DFMO was specifically antagonized by exogenous polyamines. These data suggest that polyamines are important in the growth of Candida spp. and that inhibitors of polyamine biosynthesis may be useful as antifungal agents. PMID- 3108667 TI - Genetic rescue of inviable hybrids between Drosophila melanogaster and its sibling species. AB - Post-mating mechanisms are central to the establishment of reproductive isolation between different, but closely related, species. Post-mating isolation mechanisms include hybrid breakdown, hybrid sterility and hybrid lethality and may, in some cases, be reinforced by pre-mating mechanisms such as ethological differentiation. In the Drosophila melanogaster species sub-group post-mating reproductive isolation is ensured by both the inviability and the sterility of hybrids. For example when D. melanogaster females are crossed to D. simulans males the hybrid progeny are normally all female; the hybrid males die as third instar larvae. The viable hybrid females are totally sterile. Little is known of the genetic basis for either hybrid sterility or hybrid inviability, although Coyne and others have begun a genetic analysis of the sterility of hybrids within this species sub-group. We have discovered a single gene difference that rescues the otherwise inviable male hybrids from the cross between D. melanogaster females and males of its three closest relatives. The study of this locus may shed light on the genetic control of both speciation and development. PMID- 3108668 TI - Signal requirements in the step-wise functional maturation of cytotoxic T lymphocytes. AB - The generation of effector cytotoxic T lymphocytes from resting precursors proceeds through a series of steps in a pathway that, in aggregate, involves both proliferation and development of cytotoxicity. To understand the relationship of the various signals (mitogens and/or lymphokines) that bring about progress along this pathway, it is desirable to define a series of 'minimal signals', each of which stimulates the cell to proceed to a further stage in this process of differentiation. Stimulation of lymphocytes with two different monoclonal antibodies directed against the CD2 surface molecule induces a proliferative response; we report here that both CD4+ and CD8+ cells proliferate in response to such a stimulus but do not develop cytotoxicity. Addition of recombinant gamma interferon (rIFN-gamma) or recombinant IL-2 (rIL-2) to the activated cells leads to acquisition of cytotoxic status by the CD8+ cells but not the CD4+ cells. The availability, in addition to precursors and effectors, of an apparently intermediate stage in the form of proliferating CD8+ cells that are non-cytotoxic should facilitate both cellular and molecular studies of this maturation pathway; the differences between CD4+ and CD8+ cells in development of cytotoxicity under these experimental conditions is a valuable model for understanding differentiation of T lymphocytes. PMID- 3108669 TI - HLA-DQ is epistatic to HLA-DR in controlling the immune response to schistosomal antigen in humans. AB - Antigens that produce an antibody response in some members of a species may fail to do so in others. The response to an antigen is controlled by a gene termed the immune response (Ir) gene, which is transmitted as a single dominant trait. We have provided evidence for similar immune suppression (Is) genes which control non-responsiveness through the antigen specific suppressor T cell. The non responsiveness is also dominantly inherited and the Is genes are linked to the histocompatibility (HLA) antigen system. Here we report that the HLA-DR2 molecule from a non-responder haplotype (HLA-Dw12-DR2-DQwl) is required for the proliferative T cell response to schistosoma japonicum (Sj) antigen, as a restriction element, indicating that the HLA-DR2 is the product of the Ir gene, and that the HLA-DQwl molecule of the non-responder haplotype is important in the antigen-specific suppression of the response to this antigen, suggesting that it is the product of the Is gene. We therefore conclude that the HLA-DR and DQ molecules, which are controlled by the distinct genes in the MHC multigene family, regulate immune response and immune suppression and that the gene for HLA DQ is epistatic to that for HLA-DR in controlling the immune response to schistosomal antigen in humans. PMID- 3108670 TI - Genentech falls at the last fence in race to market heart drug. PMID- 3108672 TI - Interleukin-2 receptor proteins. PMID- 3108671 TI - TPA patent battle rages in United Kingdom. PMID- 3108673 TI - Chromaffin cell synapsin? PMID- 3108674 TI - A second human interleukin-2 binding protein that may be a component of high affinity interleukin-2 receptors. AB - Although activated human T and B lymphocytes express both high-affinity and low affinity membrane receptors for interleukin-2 (IL-2), the structural features that distinguish these receptors have remained unresolved. The high-affinity receptors appear to mediate IL-2 induced T cell growth and internalization of IL 2, whereas no function has yet been ascribed to the low-affinity receptors. The Tac antigen is an IL-2 binding protein of relative molecular mass 55,000 (Mr 55K) that participates in the formation of both high- and low-affinity receptors. But Tac complementary DNA transfection and membrane fusion studies have suggested that additional T-cell components are required to produce high-affinity IL-2 receptors. In this study, we report the identification of a second human IL-2 binding protein that (1) has an Mr of approximately 70K, (2) lacks reactivity with the anti-Tac antibody, (3) binds IL-2 with intermediate affinity and (4) is present on the surface of resting T cells, large granular lymphocytes (natural killer cells), and certain T and B cell lines in the absence of the Tac antigen. Chemical crosslinking of 125I-labelled IL-2 bound to high-affinity IL-2 receptors produces labelling of both the p70 protein and the Tac antigen and the anti-Tac antibody blocks the crosslink detection of both of these proteins. Expression of Tac cDNA in a T cell line expressing the p70 protein, but lacking both Tac and high-affinity receptors, results in the reconstitution of high-affinity IL-2 receptors in these cells. Together, these findings suggest that the high-affinity human IL-2 receptor may be a membrane complex composed of at least the p70 protein and Tac antigen. PMID- 3108676 TI - Clinical decision making in a cost conscious era. Cost effective evaluation of clinical decision making. PMID- 3108675 TI - Release of neuropeptide Y (NPY) induced by tyramine in the isolated vas deferens of rat. AB - The effect of tyramine on the isolated vas deferens of rats was investigated. Tyramine induced a dose-dependent contraction which was blocked by phentolamine and disappeared in adrenergic denervated tissues. In the presence of an antiserum to neuropeptide Y (NPY), the contraction induced by concentrations of tyramine greater than 10 microM was markedly increased. In addition to inducing the release of 3H-norepinephrine (NE), tyramine evoked a concentration-dependent efflux of NPY-like immunoreactivity (NPY-LI) from synaptosomal preparations. This action was not modified either by the removal of calcium ion from the medium or by the pretreatment with tetrodotoxin (0.5 microM). Desipramine suppressed the NPY-LI release induced by tyramine apparently by the inhibition of the uptake of tyramine is suggested by the significant positive correlation between the reduction of 14C-tyramine uptake and the inhibition of NPY-LI release induced by desipramine (r = 0.946). Therefore, we suggest that tyramine does induce the release of NPY from rat vas deferens, in addition to effecting NE secretion. PMID- 3108677 TI - [Hearing loss in young people is not always innocent]. PMID- 3108678 TI - [The clinical diagnosis of "undernourished"]. PMID- 3108679 TI - [Various forms of hepatitis and their prevention]. PMID- 3108680 TI - [Antimicrobial prophylaxis in surgical interventions]. PMID- 3108681 TI - [A patient with meningococcal meningitis and deficiency of the 7th factor of the complement system]. PMID- 3108683 TI - [Isolated petit mal status at 48 years of age caused by hypochloremic hypokalemic alkalosis]. PMID- 3108682 TI - [Oxalate-induced encephalitis following hypercaloric parenteral feeding]. PMID- 3108684 TI - Haemolytic-uraemic syndrome associated with mitomycin-C treatment. PMID- 3108685 TI - Severe side effects of the cytotoxic drug mitomycin-C. PMID- 3108686 TI - [Experimental paraplegia]. AB - In this review of spinal cord injury research, the authors have selected contributions including their own research in electrophysiological changes after impact, which in their opinion best represent modern experimental concepts regarding the physiopathological mechanism of spinal cord injuries. The discrepancy between immediate electrophysiological changes and progressive hemorrhagic necrosis of the spinal cord could offer a rational treatment at the acute stage of spinal cord injury. PMID- 3108687 TI - Effect of AF64A on cerebral oxygen consumption in young and old rats. AB - Regional brain O2 consumption was determined in conscious Fischer-344 rats 3- and 33-months of age after intrahippocampal injection of the selective presynaptic cholinergic neurotoxin AF64A to investigate the influence of acetylcholine on this parameter. Regional cerebral blood flow (rCBF) was determined with 14[C] iodoantipyrine. Regional arterial and venous oxygen saturation was measured microspectrophotometrically. Regional cerebral oxygen consumption was calculated by multiplying rCBF and cerebral oxygen extraction. Systemic hemodynamic and blood gas parameters were not altered by aging or AF64A. Aging or sham injection per se did not have any significant effect on rCBF, oxygen extraction and cerebral oxygen consumption. In 3-month-old AF64A-treated rats, rCBF, oxygen extraction or cerebral oxygen consumption were significantly lower than in the control group of the same age. Old AF64A-treated animals demonstrated a significant decrease in rCBF and cerebral oxygen consumption but not in cerebral oxygen extraction when compared to the sham-lesioned group of the same age. Oxygen consumption was significantly decreased by AF64A in each examined region of both young and old groups of rats, although the decreases were less severe in the older rats. This may be related to the lesser influence of the cholinergic system on cerebral oxygen consumption in old animals or a decreased toxicity of AF64A in older animals. PMID- 3108689 TI - [A case of typical absence attacks in an 18-month-old child successfully treated with nitrazepam with a 7-year follow-up]. PMID- 3108688 TI - Effect of cytidine on the modification of phospholipid metabolism induced by ischemia. AB - [1-14C-]Arachidonic acid was injected into the lateral ventricle of the gerbils (meriones unguiculatus) two hours before producing brain ischemia by the bilateral ligation of the carotid arteries. Ten minutes before the carotid ligation a group of animals received an additional intraventricular injection of cold cytidine (2.5 mumol/brain). Control animals with and without cytidine, together with the ischemic group, were decapitated directly into liquid nitrogen ten minutes after carotid ligation or sham surgery. Cytidine is able to both stimulate arachidonic acid incorporation into lipids and noticeably correct the release of this acid from polar lipids induced by ischemia. Based on these findings, it is possible to assume that cytidine exerts an effect on the biosynthesis of phosphoglycerides as well as on their catabolic activities. PMID- 3108691 TI - Dual action of dopamine on growth hormone release in vitro. AB - The effect of dopamine (DA) on growth hormone (GH) release was studied in perifused freshly dispersed rat anterior pituitary cells. Pulses of DA (0.01-100 nmol/l), each applied for 30 min, resulted in a prompt rise in GH release. This effect was reversible, concentration-dependent and partially antagonized by metoclopramide, a DA antagonist. The effect of DA was further tested on GH stimulated secretion by human GH-releasing factor (hGRF). Perifusion with hGRF (6.25 pmol/l) for 2 min elicited an immediate rapid increase in GH release which lasted 20 min. Pretreatment of cells with DA (100 nmol/l) for 10 min and a subsequent hGRF challenge during continuation of DA perifusion significantly reduced the effect of hGRF pulses on GH release. The present data suggest that DA has direct opposite actions at the somatotroph level, stimulating the basal GH release and inhibiting the hGRF-induced GH secretion, and may thus be an important modulator of GH release. PMID- 3108690 TI - Restraint stress decreases the neurosecretory activity of tuberoinfundibular dopaminergic neurons in young but not in aged female rats. AB - The regulation of prolactin secretion by tuberoinfundibular dopamine (DA) neurons appears to be altered in the aged rat: the concentration of prolactin in the serum increases and the activity of the tuberoinfundibular DA neurons decreases. In the young female rat a brief period of stress reduces the tuberoinfundibular DA neurosecretory activity and increases the secretion of prolactin. The purpose of the present study was to determine if the responsiveness of tuberoinfundibular DA neurons to restraint stress is altered in the aged female rat. The activity of these neurons was estimated from the rate of DA synthesis in their terminals in the median eminence, as measured by the rate of accumulation of dihydroxyphenylalanine (DOPA) after the administration of a decarboxylase inhibitor. Thirty minutes of restraint stress increased serum prolactin concentrations in both young (3 months) and aged (26 months) constant estrous rats, but reduced the rate of DOPA accumulation in the median eminence of only the young rats. Restraint also decreased the rate of DOPA accumulation in the median eminence of intermediate-aged rats (14 months) independently of whether the rats were exhibiting normal ovarian cycles (measured on the day of estrus) or were in a constant estrus. This suggests that the loss of ovarian cyclicity per se is not associated with the age-related change in the response of tuberoinfundibular DA neurons to restraint stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108692 TI - Coexistence of hGHRF and NPY immunoreactivities in neurons of the arcuate nucleus of the rat. AB - The distributions of perikarya exhibiting human somatocrinin (hGHRF) and neuropeptide Y (NPY) like immunoreactivities (IR) were compared in the arcuate nucleus of colchicine-treated rats. The majority of hGHRF perikarya was found to exhibit simultaneously NPY IR, while virtually no NPY IR was detected in the external layer of the median eminence. It is suggested that the majority of the hGHRF neurons of the rat arcuate nucleus constitutes a tubero-extra infundibularly projecting system. PMID- 3108694 TI - Hyperbaric oxygen or DMSO for cerebral ischemia. PMID- 3108693 TI - The activity of 1-naphthol-UDP-glucuronosyltransferase in the brain. AB - Cerebral microsomes catalysed efficiently the glucuronidation of 1-naphthol, this formation of glucuronide being activated by treatment with Triton X-100 or digitonin. Activated microsomes from the brain of the rat conjugated 1-naphthol with an apparent Km of 95 microM and a Vmax of 5.47 nmol/hr mg protein at 30 degrees C. Microsomal uridine diphosphate (UDP)-glucuronosyltransferase activity in brain towards 1-naphthol was not significantly induced by pretreatment of animals with 3-methylcholanthrene or phenobarbital. These data suggest that UDP glucuronosyltransferases in brain are different from the hepatic enzymes with regard to biochemical parameters and in response to inducers of drug metabolism. The hepatic UDP-glucuronosyltransferase deficiency in Gunn rats was also observed in the brain. PMID- 3108695 TI - Effects of six weeks' neuroleptic treatment on the pituitary-thyroid axis in schizophrenic patients. AB - In order to investigate the effects of 6 weeks' neuroleptic treatment on the pituitary-thyroid axis in 25 male schizophrenic patients, and the diurnal variation in the thyrotropin (TSH) and prolactin (PRL) responses to thyrotropin releasing hormone (TRH) in these patients, the TRH stimulation test was performed in each of them at 14.00 and 24.00 h of the same day, both before and after 6 weeks' treatment with neuroleptics (chlorpromazine or fluspirilene). Also, serum thyroxine (T4), in vitro radioactive triiodothyronine uptake (RT3 U) and free thyroxine index (FTI) values were estimated from the pre-TRH blood sample. We found no evidence of diurnal variation in the TSH response to TRH in the schizophrenic patients, before or after 6 weeks' neuroleptic treatment. Only drug free schizophrenic patients had significantly higher PRL responses to TRH at 14.00 h than those at 24.00 h. After 6 weeks' neuroleptic treatment, schizophrenic patients tended to have lower FTI values; also, they had significantly higher basal TSH and PRL values, as well as significantly augmented TSH and PRL responses to TRH, in comparison to their pretreatment values. These findings render possible the diagnosis of subclinical hypothyroidism in neuroleptic-treated schizophrenic patients. PMID- 3108696 TI - Concepts of absence epilepsies: discrete syndromes or biological continuum? AB - There are two current approaches to the clinical conceptualization of the generalized epilepsies. The syndromic approach attempts to subdivide the patient population into relatively homogeneous groups, largely on the basis of clinical and EEG criteria. In contrast, the neurobiological approach aims to formulate a unique profile for each patient by incorporating particulars of the patient onto the background of knowledge regarding the etiologic factors important in generalized epilepsy. The value of these two approaches is discussed with regard to the dual aims of, first, improving the understanding of generalized epilepsy, and second, providing a precise diagnosis, an accurate prognosis, and optimal treatment for the patient. PMID- 3108697 TI - Vascular abnormalities in the central form of neurofibromatosis. PMID- 3108698 TI - AIDS. Case for diagnosis series, 1987. PMID- 3108699 TI - Smoking cessation guidelines for the military health care provider. PMID- 3108700 TI - Computer-assisted identification of Vietnam War dental remains. PMID- 3108701 TI - An evaluation of a collapsible plastic blood shipping container. PMID- 3108702 TI - Minnesota Multiphasic Personality Inventory profiles of enlisted Air Force and Army men arrested for driving while intoxicated: a comparison of single- and multiple-incident offenders. PMID- 3108703 TI - Retrieval methodology for Navy inpatient records. PMID- 3108704 TI - Smoking habits of U.S. military personnel. PMID- 3108705 TI - Emergency readiness training at the Uniformed Services University of the Health Sciences. PMID- 3108706 TI - Adult Plasticylinder circumcision. PMID- 3108708 TI - Anxiety, locus of control, and satisfaction in patients undergoing ambulatory surgery. PMID- 3108709 TI - Postmortem immunodiagnosis of cobra bite in a Marine. PMID- 3108707 TI - Collagenous colitis. PMID- 3108710 TI - Occult cecal perforation as cause of necrotizing infection. PMID- 3108711 TI - Case for diagnosis. Lymphoplasmacytic lymphoma. PMID- 3108712 TI - A unique training opportunity: medical care as a joint venture between a health services command community hospital and a forces command evacuation hospital. PMID- 3108713 TI - AIDS. Case for diagnosis series, 1987. PMID- 3108714 TI - Psychiatric consultation to community-based military child protection teams. PMID- 3108715 TI - Care delivery in dental residency programs. PMID- 3108716 TI - Impact of troop dental health on combat readiness. PMID- 3108717 TI - United States Navy Surgical Research Republic of Vietnam 1966-1970: a retrospective review. PMID- 3108718 TI - An assessment of preventable morbidity in the U.S. Army, Europe. PMID- 3108719 TI - Will cost-sharing improve the military health care delivery system? PMID- 3108720 TI - A comparison of sprain and strain injury rates during aerobic/calisthenic and aerobic/circuit weight training programs. PMID- 3108721 TI - Malingering in the military: understanding and treatment of the behavior. PMID- 3108722 TI - Bacteremic pneumonia after fiberoptic bronchoscopy. PMID- 3108723 TI - Pyridoxalated polymerized stroma-free hemoglobin solution (SFHS-PP) as an oxygen carrying fluid replacement for hemorrhagic shock in dogs. PMID- 3108724 TI - Case for diagnosis. Desmoplastic (or central) fibroma, left proximal fibula. PMID- 3108725 TI - Post-traumatic epilepsy in the military. PMID- 3108726 TI - [Total parenteral nutrition in surgical patients. Our experience]. PMID- 3108727 TI - [Early postoperative total parenteral nutrition using naso-jejunal catheters in digestive surgery: an alternative to nutritional jejunostomy]. PMID- 3108728 TI - Operative treatment of persistent lateral instability of the ankle--is it worse to sprain the ankle than to break it? AB - A series of 1600 patients suffering from injury to the lateral ligaments of the ankle were treated conservatively with plaster and bandages. In 35 cases the instability persisted and these patients required a Watson-Jones repair. This repair yielded a successful result in over 90% of cases. PMID- 3108729 TI - The hypothalamus receives major projections from the tuberomammillary nucleus in rat. AB - Projections from the tuberomammillary nucleus (TM) to widespread regions within the hypothalamus were evaluated using a combined immunohistochemical-retrograde fluorescent tracing procedure. Injections of Fluoro-gold into the anterior hypothalamus labelled TM neurons identified by their immunoreactivity for the enzyme adenosine deaminase (ADA). Small injections of Fluoro-gold into the posterior hypothalamus also led to the labelling of TM neurons. The numbers of ADA-immunoreactive axonal varicosities were 5 times greater in the hypothalamus than in most other brain regions. The results indicate that the hypothalamus represents a major projection area of the TM. PMID- 3108731 TI - Weighing the costs and the benefits of student education to service agencies- Part 2. PMID- 3108730 TI - Phencyclidine-induced head-twitch responses as 5-HT2 receptor-mediated behavior in rats. AB - This study was designed to assess whether phencyclidine (PCP)-induced head-twitch was antagonized by ritanserin, a selective serotonin (5-HT2) receptor antagonist, in mice and rats to confirm the involvement of 5-hydroxytryptamine (5-HT) neurons in PCP actions in comparison with 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) induced behavior. PCP (7.5, 10 and 12.5 mg/kg, i.p.)-induced head-twitch was completely antagonized by ritanserin (1 mg/kg, s.c.) in mice and rats, and 5 MeODMT (2 and 4 mg/kg, i.p.)-induced head-twitch was also completely antagonized by ritanserin in mice. PCP and 5-MeODMT induced head-weaving in mice after ritanserin treatment, but this did not occur in rats. In rats, 5-MeODMT failed to induce head-twitch. These results suggest that PCP-induced head-twitch response in rats is developed via 5-HT2 receptors and it is a useful 5-HT2 receptor model, while 5-MeODMT-induced head-weaving in rats is developed via 5-HT1 receptors and is a useful 5-HT1 receptor model. PMID- 3108732 TI - Role of parenteral nutrition in the very-low-birth-weight infant. PMID- 3108733 TI - Mexitil and cross-allergenicity. PMID- 3108734 TI - Lithium poisoning. PMID- 3108736 TI - Absolute quantification of pharmacokinetic distribution of RES colloids in individuals with normal liver function. AB - Estimates of the radiation dose resulting from liver-spleen scintigraphy 99Tcm labelled colloids are based on pharmacokinetic data mainly determined in animals. The aim of this study was to check the pharmacokinetic data by direct, absolute in vivo quantification in man. For this purpose appropriate methods of measurement were developed, or procedures taken over from literature were modified. Liver and spleen activities were directly measured using a double energy window technique. Activities in other organs were quantified by conjugate whole-body scans. All measurement procedures were checked using the whole-body Alderson phantom. Pharmacokinetic data for sulphur colloid, tin colloid, human serum albumin (HSA) millimicrospheres, and phytate were obtained in 13 to 20 normal subjects for each type of colloid. Depending on the colloid type liver uptake was between 54 and 75% of the total administered dose (TAD) and spleen uptake was 3.5 to 21% TAD. Activity measured in blood, urine, lung and thyroid proved to be far from negligible. The results of this work suggest a correction of the animal-based data of colloid distribution and radiation dose on the basis of the direct measurement of absolute uptake in man. PMID- 3108735 TI - Cyclooxygenase inhibition and improved oxygenation in patients with pulmonary complications of AIDS. PMID- 3108737 TI - The case for case management. PMID- 3108738 TI - 5-Fluorouracil, 4-epidoxorubicin, and mitomycin C (FEM) combination chemotherapy for advanced gastric carcinoma. A phase-II trial by the "chemotherapiegruppe gastrointestinaler tumoren (CGT)". AB - In a phase-II-trial 40 patients with advanced gastric cancer were treated with 5 fluorouracil, 4-epidoxorubicin, mitomycin C (FEM) combination therapy. Twenty five out of 30 patients with measurable disease were evaluable for response after 8 weeks of treatment. Seven patients achieved a partial remission (PR), suggesting a response rate of 28%. Ten patients had no change (NC) and 8 patients showed progression (P). The median time to progression for patients with PR was 7.2 months and for patients with NC 6.3 months. Median survival time for all patients was 5.3 months, for patients with PR and NC 9.9 months. WHO grade 3 toxicity appeared in 3% (WBC and nausea/vomiting) and 15% (alopecia) of patients. The data suggest that this regimen is not more active, but is better tolerated than the original FAM schedule. Therefore it seems suitable for out-patient treatment, for elderly patients and for those who cannot be treated by more aggressive drugs. PMID- 3108739 TI - Cost-effective cataract surgery in developing nations. AB - Today approximately twenty million people are blind (visual acuity less than 3/60 [10/200]) and tens of millions more are visually disabled (visual acuity less than 6/18 [6/60]) from cataract. Most of these people live in impoverished developing nations. The logistics of providing cataract surgical care for them are complex. Simplifying the cataract operation, employing appropriate technology, and training non-physicians in intraocular surgery is efficient cost effective strategy in many developing African nations. PMID- 3108740 TI - Modern lateral external beam (lens sparing) radiotherapy for retinoblastoma. AB - A standard 6 MV linear accelerator X-ray beam has been adapted to produce a non divergent and almost penumbra-free beam edge by a beam splitting and extended collimation system. Using a contact lens to provide the reference point on the front surface of the eye and an attached rod-and-scale measuring system that is linked to the sharp beam edge system, it has proved possible to place this field border with an exactitude of within 0.5 mm at a required distance behind the front surface of the eye. This system has been developed for the treatment of small retinoblastomas not amenable to focal treatment methods; the technique may have other applications. Data in this manuscript corroborate an earlier Dutch publication and extend the observations on the physics beam profile obtainable, the immobilization of the patient, the anaesthetic procedure, the contact lens system and the dose prescription. Both scanning densitometry and TLC measurements in an anthropomorphic head shell (with extractable eye) confirm the extreme precision and sharp beam profile obtainable by this technique. PMID- 3108741 TI - Chemical sterilizing/disinfecting solutions. Which ones are best for what? PMID- 3108742 TI - The effect of indomethacin on tumor regression in DMBA-induced epithelial neoplasia of hamster cheek pouch mucosa. AB - Tumors were allowed to develop in the cheek pouches in two groups of hamsters following topical application three times per week of a 0.5% solution of 7, 12 dimethylbenz(alpha)anthracene (DMBA) in liquid paraffin administered for 10 weeks. Two control groups received no DMBA treatment. After carcinogen application, the animals in one DMBA-treated group and those in one of the control groups were given indomethacin daily; this was administered through the oral route for an additional 10 weeks. At this time, all of the animals were killed and their cheek pouches, the draining cervical lymph nodes, and other organs were removed for examination. The number and size of tumors in each pouch were recorded, and each pouch was weighed. Indomethacin, in the dosage administered, was not found to cause regression of established tumors. The effects of prostaglandins, indomethacin, and other prostaglandin-synthesis inhibitors in tumor tissue are discussed. It is suggested that more knowledge is needed about the role of prostaglandins, and the related products of AA metabolism, in squamous cell cancer before indomethacin is used therapeutically. PMID- 3108743 TI - Medical complications in psychiatric patients as demonstrated in a patient with AIDS. PMID- 3108745 TI - Psychiatric assessment in the home: applications in home care. AB - Home evaluation of the client experiencing psychiatric problems is a complex task, but it does not have to be an overwhelming or impossible one. Home care nurses, with their broad assessment skills and ability to make independent decisions, are in the ideal position to assess and detect the presence of clients' psychiatric problems. Although the psychiatric clinical nurse specialist (or mental health nurse practitioner) can be an important resource, it is the nurse, who is in the home daily, who has the advantage of really knowing the client and recognizing early signs of emotional/mental distress. Through early recognition of problems, thorough assessments, and appropriate planning, the client experiencing psychiatric problems in the home will receive the care he or she deserves. PMID- 3108744 TI - Analyzing patient satisfaction: a multianalytic approach. AB - A telephone survey of 9% of first quarter discharges at The New York Hospital was undertaken to identify the dimensions of a patient satisfaction questionnaire and the determinants of patient satisfaction. The questionnaire included measures of overall satisfaction with hospital services, satisfaction with ten aspects of service, and patient expectations. Relatively high inter-item correlations indicate that the questionnaire can be shortened and the same overall dimensions measured. A longer questionnaire would still be necessary to ascertain the relative values of measures within any one dimension. The best determinants of overall satisfaction with hospital care appear to be patient expectations and satisfaction with nursing care. Patient satisfaction with nursing care, however, seems to hinge on satisfaction with services not under a nurse's control. PMID- 3108746 TI - Case classification and quality of care: issues to consider before making the investment. AB - Hospitals are considering adoption of patient classification systems, in part, because of their desire to create a clinically meaningful data base for quality assurance and monitoring. But before they make the substantial financial investment such a system requires, hospital personnel should be sure it is appropriate for their institution. The system should be reliable, medically meaningful, and useful in differentiating cases in which care was poor. The classification components should be easily available from the hospital's standard information. The cost of the system and its impact on staff should also be considered. PMID- 3108748 TI - [Economic aspects of the treatment of patients with fractures of the upper and lower extremities]. PMID- 3108747 TI - Health maintenance organizations and the elderly: the potential for vertical integration of geriatric care. PMID- 3108749 TI - [Evaluation of radioimmunoassay studies in the presence of thyroxine-binding autoantibodies and in euthyroid thyroxine-binding globulin deficiency]. PMID- 3108750 TI - Update on AIDS. PMID- 3108751 TI - Oculopharyngeal muscular dystrophy: clinical and histopathologic correlations. AB - Oculopharyngeal muscular dystrophy is an autosomal dominant myopathy that exhibits the symptoms of progressive dysphagia, with ptosis usually occurring after the age of 40. Literature review of this rare disease reveals a high incidence in the French-Canadian population, as well as in five other ethnic groups. Our article details the clinical history and genealogy of the disease through four generations in a family of English descent. Radiographic studies show a cricopharyngeal bar and aspiration. Results of electron microscopic examination of muscle biopsy specimens from the vastus lateralis and cricopharyngeus muscles confirm a chronic, active, severe, myopathic process that is more pronounced in the cricopharyngeus muscle. The recommended treatment for blepharoptosis and the cricopharyngeus muscle pathosis is discussed. PMID- 3108752 TI - Transcutaneous electrical stimulation of the recurrent laryngeal nerve: a method of controlling vocal cord position. AB - This study was designed to examine the feasibility of transcutaneous stimulation of the recurrent laryngeal nerve. Electrical activation of the recurrent laryngeal nerve was achieved by applying a blunt electrode to the intact neck skin at specific points along the tracheoesophageal groove in anesthetized adult dogs. The stimulus consisted of 10 mA cathodal pulses, each of 1 msec duration, delivered at a frequency of 10 Hz and increased by 10 Hz increments up to 100 Hz. Vocal cord excursion was directly related to the frequency of applied current. In all six dogs studies, stimulation at 30 Hz resulted in maximal ipsilateral vocal cord abduction, while stimulation at frequencies greater than 40 Hz resulted in ipsilateral vocal cord adduction up to or across the midline. Vocal cord movement was immediate and persisted for the duration of the stimulus train. Surrounding neck muscles were not visibly activated. We propose that the observed frequency dependent movement of the vocal cords occurred because of the difference between the contraction times of the intrinsic abductor and adductor muscles of the larynx. Transcutaneous recurrent laryngeal nerve stimulation appears promising, both as a diagnostic aid in laryngoscopy and as a therapeutic tool in controlling the glottic aperture. PMID- 3108753 TI - Carcinoid tumor of the larynx: case report and review of the world literature. AB - The clinical, light microscopic, and ultrastructural features of a carcinoid tumor occurring in the larynx of an 80-year-old man are presented and compared with 22 laryngeal carcinoids described in the world literature. These 23 tumors occurred in persons from 45 to 80 years of age (mean age was 61 years) and were three times more common in men than in women. Hoarseness was the most common presenting symptom. Sixty-one percent of the tumors were supraglottic, 26% were transglottic, 4% were glottic, 4% were subglottic, and 4% were unspecified. At least 15 (65%) of the patients are known to have developed metastases. Nine of these (60%) presented with only regional lymph node metastases, one of which was occult. Surgery is the treatment of choice, with the extent dependent on the stage of disease. Radiation therapy appears ineffective, and chemotherapy is largely untested. The 2- and 4-year determinate survival rates were 59% and 25%, respectively. PMID- 3108754 TI - Immunology of foods. AB - Investigation of food sensitivity is difficult and often confusing. However, there are multiple articles in the literature which illustrate that food is absorbed from the gastro-intestinal tract in an antigenic fashion and that the entire immune system is stimulated by these antigenic food particles. All four Gell and Coombs varieties of immunologic reactions have been demonstrated as causes of symptoms in patients. Test techniques are available for each of these immunologic reactions, as is treatment for their noxious effects. PMID- 3108756 TI - Postauricular undersurface tympanic membrane grafting: some modifications of the "swinging door" technique. AB - Following Palva's original description of the technique, the "swinging door" tympanoplasty was modified and reported by several otologic surgeons, including Glasscock, Fisch, Smyth, and Pennington. The basic technique involves the elevation of superiorly based and inferiorly based canal skin flaps, or "swinging doors." After dividing the posterior anulus, the flaps are rotated anteriorly, a maneuver that provides ample exposure of the middle ear and greatly simplifies underlay fascia grafting. The purpose of this article is to review this basic technique and to describe additional modifications that further simplify tympanoplasty grafting. These modifications include canal flap advancement, the use of multiple fascia grafts, techniques for securing the graft to the malleus handle, and the use of tragal cartilage in grafting. With this technique, a 95% take rate was observed at 3 months, and the graft was firmly attached to the malleus handle in all cases. PMID- 3108755 TI - Subrenal capsule assay for squamous cell carcinoma of the head and neck. AB - The murine subrenal capsule assay is an in vivo method for determining the responsiveness of solid tumor xenografts to chemotherapeutic agents. It was used in this study for the purposes of constructing growth curves of squamous cell carcinoma of the head and neck and collecting pilot data on the effects that indomethacin and cisplatin have on this malignant condition. Nine of the ten assays performed were evaluable. Indomethacin, cisplatin, or both were used as treatment drugs in each assay. One-millimeter fragments of viable tumor, from patients with head and neck squamous cell carcinoma, were implanted beneath the renal capsules of normal immunocompetent mice. Baseline and posttreatment measurements were made of the xenografts, and response to treatment was determined by comparing changes in tumor sizes of the test and control groups. Results indicated that reduction in tumor sizes occurred in indomethacin-treated mice in four assays and in cisplatin-treated mice in six assays. In addition, two separate growth curves were calculated by plotting the mean change in tumor size in five mice per day on days 3 through 7. In conclusion, the subrenal capsule assay is a relatively rapid and inexpensive assay in which squamous cell carcinoma remains viable and therapeutic agents can be tested. However, clinical trials that use this assay to choose treatment drugs are needed in order to correlate assay results with clinical responses. PMID- 3108757 TI - The effect of butyl 2-cyanoacrylate on the middle and inner ear of the chinchilla. AB - Butyl 2-cyanoacrylate was placed on the oval and round window of the ear of the chinchilla and was also used as an adhesive for myringoplasty with autogenous muscle fascia. Butyl 2-cyanoacrylate was found to be difficult to manipulate and moderately toxic to the middle ear; there were occasional significant reactions in the inner ear. PMID- 3108758 TI - Oral steroid therapy for chronic middle ear perfusion: a double-blind crossover study. AB - A prospective, double-blind crossover study design was used in the evaluation of the role of prednisone in the treatment of a chronic middle ear effusion. Sixty children with an effusion--of at least 2 months' duration--randomly received either prednisone or placebo for 2 weeks. One week later they were re-evaluated. If the effusion had resolved, they were followed periodically; if the effusion persisted, they were given the crossover regimen and reevaluated. Sixty percent of the patients' effusions cleared, but there was no statistical difference between the prednisone and placebo groups. The amount of hearing recovery was also the same for both treatment regimens. Subdividing the patients on the basis of effusion duration, unilateral vs. bilateral effusions, or history of ventilation tubes or antibiotics failed to identify a subgroup of individuals who might benefit from a short-term course of oral steroids. PMID- 3108759 TI - Fluorescein elimination as a measure of island flap perfusion. AB - The fluorescein test has been used as a means of assessing flap viability for almost 40 years. This study was performed in an attempt to determine if recording of the elimination of dye--combined with dye uptake measurement--could provide reliable and consistent monitoring of island flap perfusion. PMID- 3108760 TI - Speech performance by patients with multichannel cochlear implants. AB - Thirteen patients were implanted with multichannel cochlear implants between April 1, 1984 and February 25, 1985. The patients are fitted with the sound processor unit 4 to 6 weeks postsurgery. One patient had a single-channel unit replaced with a multichannel implant. She reported improved sound quality. All patients use their implants daily and all patients would undergo implantation again (based on their current performance). Evidence exists that continued use leads to improved performance. Patient S.S. progressed from auditory-only scores of 12% and 24% to 100% in 4 months. The average open set auditory-only performance of six patients in the first 4 months on a spondee word list was 22%. The average of eight patients--more than 4 months post sound processor--is 44%, indicating improvement with use. Patients perform better when combining auditory input with visual input than they do with lip reading alone. The multichannel implant is well tolerated and accepted, and results in speech performance improvement. PMID- 3108761 TI - Influence of cisplatin on wound healing--an experimental model. AB - Recent clinical studies have shown that adjuvant chemotherapy may improve response rates to treatment for advanced head and neck carcinomas. Given preoperatively, some chemotherapeutic agents adversely affect wound healing. The specific purpose of this study was to evaluate the influence of cisplatin on wound healing when it is given preoperatively. Forty-four Swiss outbred mice were divided into control and treatment groups. One week before surgery, the treatment group received cisplatin (2 mg/kg body weight) by subcutaneous injections on 2 consecutive days. Each control animal was given an equal volume of normal saline. A 1.5 cm transverse incision was made in each animal, and wounds were closed with surgical staples. The mean wound-breaking strength was determined for a minimum of 5 treatment and 5 control mice on postoperative days 6, 10, 13, and 16. Serum creatinine, blood cell counts, and changes in weight were also monitored. Results showed wound strength on postoperative day 10 to be significantly reduced in mice treated with cisplatin (P less than 0.05). There was no significant difference for wound strength on any other days and all other variables were similar between both groups. In conclusion, cisplatin has an adverse effect on wound healing, the peak of which probably occurs during the proliferative stage of wound healing. Further studies are needed to determine the optimal time for surgery after preoperative chemotherapy. All new chemotherapeutic agents, particularly those being considered in a preoperative regimen, should be tested in this manner. PMID- 3108762 TI - Coronal sections of larynges from radiation-therapy failures: a clinical pathologic study. AB - Serial coronal sections of 89 wide-field laryngectomies were examined. Twenty were specimens obtained from laryngectomies to treat patients for whom primary radiation therapy failed to cure early laryngeal cancer. These specimens were compared to 69 specimens from laryngectomies for T3 and T4 laryngeal cancers. The irradiation-failure group showed a significantly greater invasion of cartilage and extension into subglottic areas. The extension of tumors along blood vessels and mucous glands appeared to contribute to the spread of tumors in the irradiation-failure group. These findings have implications for the surgical management of irradiation failures in the treatment of laryngeal cancers. PMID- 3108763 TI - The ossicle-cup prosthesis: five years later. AB - The ossicle-cup prosthesis is a semibiologic prosthesis that incorporates a synthetic portion into the remaining (or transplant) ossicle. This assembly is positioned on the stapes capitulum, with the synthetic cup forming a dynamic joint. During 1978, 114 patients underwent surgical procedures in which an ossicle cup prosthesis was used. After 1 year 84% of these patients were within 20 dB of their preoperative bone hearing levels. Patients with a concurrent mastoidectomy did worse than those who underwent only a tympanoossiculoplasty. Five years later, 74% of the successful cases were still within 20 dB of the preoperative hearing levels. Eighteen patients underwent a revision surgical procedure to regain hearing. The postoperative hearing results at 1 year were 50% within 20 dB. The causes of failure included further ossicle necrosis (28%), a laterally healed tympanic membrane (39%), and fixation of the prosthesis (33%). Extrusion of the prosthesis during the 5-year period was between 1% and 2%. Overall, the ossicle cup prosthesis has proved to be a stable assembly, easy to revise, and longlasting. Once successful, three of four cases will retain successful hearing for more than 5 years. PMID- 3108764 TI - Fibrous dysplasia of the paranasal sinuses. AB - Fibrous dysplasia (FD) of the paranasal sinuses is rare and often presents a diagnostic challenge. It is usually secondary to extension of disease from adjacent bones and is rarely limited to the sinuses. We have described three cases of FD involving the paranasal sinuses, including the first reported case of FD isolated to the sphenoid sinus. A brief update of the clinical aspects, radiographic appearance, diagnosis, and management of craniofacial FD is provided. PMID- 3108765 TI - Pediatric nasal resistance and lower anterior vertical face height. AB - In an effort to determine whether nasal obstruction in the pediatric population influences craniofacial and orthodontic development, nasal resistance data were collected from 211 consecutive orthodontic patients by means of active anterior rhinometry. Age-specific nasal resistance standards had been previously accumulated from an unselected representative sample of 498 youngsters, drawn from socioeconomic and demographic backgrounds similar to those of the orthodontic group. Resistance data collected from 211 orthodontic patients were found to fall in an almost linear arrangement, varying inversely with age. Age specific nasal resistance mean data were found to be consistently higher than comparable age-specific mean data of the unselected comparative sample. When orthodontic nasal resistance data were compared with cephalometric measurements of anterior lower vertical face height in 60 patients, there was a definitive correlation between elevation in nasal resistance and increased lower vertical face-height measurements. PMID- 3108766 TI - Instantaneous "video photography" with a low-cost black-and-white video printer: its value in otolaryngology and head and neck surgery. AB - Despite its shortcomings in black-and-white imagery and its print quality, the video printer described here is an inexpensive and convenient video image printing instrument and is useful for documentation of anatomy and pathologic conditions of otolaryngologic structures. It is of great value in patient counselling and in development of a permanent pictorial record. PMID- 3108767 TI - Precaution and safety in carbon dioxide laser surgery. AB - The introduction of the carbon dioxide laser--(in 1972) by Strong and Jako as a surgical tool for removal of laryngeal papilloma--heralded a new period of surgical refinement and precision in otolaryngology and also led to adjustment and precautions in operating room setup and in the administration of anesthetics. This article recounts 8 years of experience in carbon dioxide laser surgery on 3500 head and neck patients. Techniques and precautions of administering anesthetics for laser surgery are presented. The management of a laser-ignited burn is also discussed. PMID- 3108768 TI - Internal maxillary artery ligation speculum. PMID- 3108769 TI - Passy-Muir tracheostomy speaking valve. PMID- 3108770 TI - The Wiet/Meikle suction irrigation system. AB - We have used the disposable Wiet/Meikle Suction Irrigation System on more than 300 cases, including both otologic and neurotologic procedures. The device is provided as a convenience item to nursing, for those otolaryngologists practicing ear surgery. PMID- 3108771 TI - Timeliness in publication. PMID- 3108772 TI - Photodocumentation of laser microsurgery: preoperative, intraoperative, and postoperative techniques for still and video photographs. AB - Photodocumentation of preoperative, intraoperative, and postoperative findings serves to enhance and complement the study of normal and pathologic anatomy and physiology. Such documentation is invaluable for the teaching of medical students, physicians in the same or in other specialties, and allied health personnel. A surgeon may review and refine surgical technique, and colleagues around the world may study the situation from the same vantage point after surgery has been completed. Referring physicians may be kept graphically informed of the findings and progress of their patients. With the development of such modern technologies as laser microsurgery, an objective means of assessing ablation of disease and healing of surgical wounds is now available, and many of the extravagant claims of "no bleeding, and no edema during or after surgery" may be confirmed or refuted. I shall describe techniques for endoscopic examination and photodocumentation of the ears, anterior and posterior nares, nasopharynx, hypopharynx, and larynx in the preoperative, intraoperative, and postoperative patient. Techniques for obtaining high-quality color transparencies and color and sound videotapes will be presented. Equipment is simple and relatively inexpensive, and no special knowledge of photography is required. Examples of benign and malignant disease of the ears, nose, nasopharynx, and larynx will be shown before, during, and at regular intervals after microsurgery with the CO2 laser. PMID- 3108773 TI - Wound healing of true vocal cord squamous epithelium after CO2 laser ablation and cup forceps stripping. AB - A study was conducted on the effect of deepithelization of the true vocal cords; microcup forceps were used, as opposed to CO2 laser ablation. A CO2 laser, coupled to an operating microscope, was used to ablate the surface epithelium of the right true vocal cords in eight canines, while conventional microlaryngeal stripping was performed on the left true cords in the same animals. Photographs were taken immediately after injury and again before the animals were killed. Histologically, the series of true vocal cords ablated by the CO2 laser revealed granulation formation at day 5, whereas those treated with conventional stripping developed granulation at day 3, thus indicating delayed healing. Charred carbonaceous debris of CO2 laser ablation was found to cause a giant cell reaction that persisted after reepithelization. Despite the precise control offered by the laser, many of the laser-injured true vocal cords revealed vocalis muscle edema and muscle destruction. After healing occurred, dense fibrosis was found in the vocal muscle injured during CO2 laser ablation of the overlying squamous epithelium. PMID- 3108774 TI - The surgical exposure of penetrating injuries to the carotid artery at the skull base. AB - Injuries of the internal carotid artery at the skull base present complex technical problems for the surgeon. Exposure is difficult, distal control of the vessel for shunting or repair is frequently impossible, and thus ligation of the ICA is often necessary as definitive treatment. Three cases involving penetrating injury to the carotid artery at the skull base are presented. The issue of primary repair vs. ligation for carotid injuries is briefly addressed, and the various methods of surgical exposure of the distal extracranial ICA are reviewed. PMID- 3108775 TI - Hearing preservation after acoustic neuroma surgery with intraoperative direct eighth cranial nerve monitoring: Part II. A classification of results. AB - Since the advent of brainstem auditory evoked response audiometry and computerized tomography, small acoustic neuromas are more frequently found. Often the patient has serviceable hearing, which we would like to preserve during complete tumor removal. Since 1978, sixteen patients with acoustic neuromas have been operated upon through the retrosigmoid suboccipital approach, with the goal of hearing preservation. In 1983, we began using intraoperative direct eighth nerve monitoring, which produced a rapid assessment of cochlear nerve function during the excision of small acoustic neuromas. The tumors varied in size from intracanalicular lesions to one lesion with a 3.0 cm protrusion medial to the porus acousticus. In eight of sixteen cases, intraoperative monitoring was used, and in four of the patients hearing was preserved. In eight cases, intraoperative monitoring was not used, and hearing was preserved in only two patients. The overall success rate--in total tumor removal with hearing preservation--was 37%. Hearing was preserved in six of eight patients who had tumors which measured less than 1.5 cm. In this group of cases, two of the patients had a Class I good hearing result (PTA 0 to 30 dB and 70 to 100% discrimination), one patient had Class III nonserviceable hearing, (PTA 65 to 75 dB and 25 to 45% discrimination), and three patients had Class IV poor hearing, (PTA 80 to 100 dB and 0 to 20% discrimination). We found that continuous monitoring of direct eighth-nerve evoked action potentials were extremely valuable and rapidly indicated reversible cochlear nerve trauma. PMID- 3108776 TI - Ramsay Hunt facial paralysis: clinical analyses of 185 patients. AB - In a prospective study of 1507 patients, evaluated consecutively for facial palsy in the Cranial Nerve Research Clinic at the Kaiser Permanente Medical Center, Oakland, California, between 1966 and 1976, 185 cases (12%) were diagnosed as Ramsay Hunt syndrome. In 46 cases (25%), the diagnosis of herpes zoster was confirmed by acute and convalescent serum titers for varicella-zoster virus. In 139 cases (75%), viral titers were not performed and the diagnosis was based on the characteristic clinical presentation of the Ramsay Hunt syndrome. The data were subjected to multivariate analysis evaluating age, sex, race, signs, and symptoms at onset, severity of paralysis, associated medical problems with concomitant neurologic deficits, and response to therapy. These were compared with data of 1202 patients with Bell's (herpes simplex) palsy. The facial palsy of Ramsay Hunt syndrome was found to be more severe, to cause late neural denervation, and to have a less favorable recovery profile than Bell's (herpes simplex) facial palsy. Prognostic factors and treatment recommendations are discussed. PMID- 3108777 TI - Effects of nasal and laryngeal stimulation upon peripheral lung function. AB - Arterial hypoxemia and sudden death have been associated with the placement of posterior packs for control of severe epistaxis. There exists some controversy as to the mechanism underlying the clinically observed hypoxemia; some authors postulate a nasal pulmonary reflex as the basis for the hypoxemia. In an attempt to further investigate this theory, collateral ventilation was measured in the dog model during nasal and laryngeal stimulation. Collateral ventilation is thought to be one of the most sensitive techniques available to assess the resistive and elastic properties of the lung periphery. In the dog, with respiratory rate controlled (i.e., anesthetized and paralyzed), nasal stimulation with mechanical, thermal, and chemical stimuli failed to affect collateral ventilation. This finding suggests that the reflex may be acting either in larger lung segments or on the pulmonary vascular bed itself. PMID- 3108779 TI - IgG levels after treatment with antigen vials based on the scratch testing, intradermal testing, modified RAST testing. AB - In this study, there were three groups of patients--each group consisting of four patients. The first group had been skin tested by the scratch method, the second group was skin tested by the end point titration intradermal method, and the third group had been tested for inhalant allergy by the modified RAST technique. All of them had multiple treatment vials made, dependent on the type of testing they had, and the vials all included the ten inhalants that were tested for. All patients had been treated for a year with weekly immunotherapy injections. Specific IgG levels, blocking antibody levels to the ten inhalant allergens, were determined. The results were that the patients who had been scratch tested had the lowest levels of specific IgG blocking antibody--while both intradermal end point titration and modified RAST testing had much higher elevations of blocking IgG antibody, with the RAST having the highest. It is concluded that, since the treatment vials prepared after scratch testing of all the antigens are at the same concentration, there are many antigens that are not given in adequate amounts to cause a good IgG response whereas, by calibrating the concentrations of antigens in the intradermal titration and the modified RAST testing, all the antigens are being injected in sufficient quantities to get a good blocking antibody response. PMID- 3108778 TI - Magnetic resonance imaging of congenital midline nasal masses. AB - Congenital midline nasal masses are rare lesions with potential intracranial extensions. Thus, thoughtful preoperative evaluation is essential in planning the appropriate surgical approach, to prevent such complications as cerebral spinal fluid leaks and meningitis. Preoperative computerized tomographic (CT) scans are useful in visualizing bony defects, but are not well suited for soft tissue imaging. Magnetic resonance imaging (MRI) is the latest advance in cross sectional imaging technology. It offers superior soft tissue contrast, is noninvasive, and does not use ionizing radiation. It is particularly useful in imaging encephaloceles. Three cases of congenital midline masses are presented as illustrations. Two dermoid cysts demonstrate the usefulness of MRI in ruling out intracranial extension. A large encephalocele dramatically demonstrates the superiority of MRI in imaging the brain herniating into the nose. Since MRI is noninvasive and does not use ionizing radiation, it should be considered before CT scanning, to rule out intracranial extension. PMID- 3108781 TI - Low-frequency harmonic acceleration in the evaluation of patients with intracanalicular and cerebellopontine angle tumors. AB - The application of low-frequency harmonic acceleration (HA) with the rotary chair is becoming more widespread in the clinical evaluation of the vestibular system. In the last 2 years, 18 patients with surgically or radiologically confirmed intracanalicular or cerebellopontine angle tumors have been evaluated with this clinical modality. In all cases (100%)--which included seven small tumors- vestibular evaluation with HA was abnormal. Slow harmonic acceleration, as is the case with other methods of vestibular evaluation, is not specific for acoustic tumors. Its great sensitivity in detecting peripheral vestibular abnormalities, however, may make it a useful addition to the test battery in the evaluation of patients with suspected intracanalicular or cerebellopontine angle tumors. PMID- 3108780 TI - Electrical tinnitus suppression: a double-blind crossover study. AB - A wearable device for transcutaneous electrical tinnitus suppression (ETS) has recently been reported to be effective for relief of tinnitus. Twenty patients with sensorineural hearing loss and tinnitus participated in a double-blind crossover study. Both active devices and internally disconnected placebo devices, supplied by the manufacturer, were used. Reduction in severity of tinnitus was reported by 2 of 20 patients (10%) with the active device and by 4 of 20 (20%) with the placebo device. Fifteen of 20 (75%) had no relief with either device. Those who preferred the placebo device, however, reported only minimal relief, while one of the two who preferred the active device stated it had reduced tinnitus severity by 70% to 80%. This patient was recalled for a series of one hour test sessions, during which either an active or placebo device was used, according to a random schedule. On each of four on trials, the score for severity of tinnitus for each ear decreased by at least 50% (median = 70%), while in three off trials, the severity of tinnitus was unchanged or decreased by up to 30% (median = 16%). We conclude that the Theraband headset is effective for a small proportion of patients with sensorineural hearing loss and tinnitus. PMID- 3108782 TI - Complicated frontal sinusitis: evaluation and management. AB - The diagnosis and management of complicated cases of frontal sinusitis are challenging problems. Unacceptable mortality and morbidity from delay in diagnosis and treatment must be weighed against the early performance of deforming surgical procedures. Many of these patients require prolonged hospitalization for intravenous antibiotic therapy. The assessment of the optimal time course for such therapy has been difficult. Six illustrative cases of frontal sinusitis, complicated by intracranial suppuration, osteomyelitis, and/or bone erosion, are presented. The use of CT, bone, and gallium scans in the diagnosis of complications--and in the timing of antibiotic therapy and surgical intervention--are discussed. Guidelines are formulated for the evaluation and treatment of complicated frontal sinusitis. PMID- 3108783 TI - Results of surgical repair of inapparent perilymph fistulas. AB - In patients who are thought to have a perilymph (PL) fistula, careful inspection of the round and oval windows during exploratory tympanotomy may be normal. The decision must then be made either to terminate the procedure--knowing that the patient's symptoms will probably continue or deteriorate--or to repair both windows as if PL fistulas were present, risking further damage to the inner ear. From a series of 14 patients explored for possible PL fistulas, we report on 6 patients with preoperative diagnoses of PL fistula, based on history, physical examination, and audiometry. Symptoms resulting from trauma were present from 10 days to 23 years before surgery. During exploratory tympanotomy, no fistulas were evident; however, both the oval and round windows were repaired with tissue grafts. Follow up--for 1 to 5 years--revealed that vertigo was relieved in all patients. Postoperatively, one patient had a mild conductive hearing loss; yet no patient sustained a sensory neural hearing loss. We conclude that patch grafting of both the oval and round windows is a safe and effective method of treating suspected, but inapparent fistulas. Patient selection, surgical technique, and results shall be detailed. PMID- 3108784 TI - Vestibular evoked potentials in man: an overview. AB - Evoked potentials (EPs) have been used to detect auditory, visual, and somatosensory dysfunction. Evoked potentials are recorded by averaging an optimal number of responses (that are time-locked) to the same number of appropriate stimuli. Adequate stimulus levels and "minimal" response latency are necessary for recording evoked potentials. Vestibular evoked potentials have received considerably less attention because of the difficulty in providing appropriate stimuli, the relatively long latency of vestibular responses, and the adaptation of the vestibular system to repeated stimulation. Technological advances have made it possible to provide accurate stimuli by use of computer-controlled rotating chairs and computer-averaging procedures. PMID- 3108785 TI - Mesenchyme remaining in human temporal bones. AB - This study was conducted in order to gain basic information about mesenchyme remaining in the middle ear cleft in normal infants. Because no previous report has objectively described the quantity or quality of such postnatal remnants in normal infants, it has not been possible to accurately evaluate the significance of mesenchyme remaining in the middle ears of infants with pathologic conditions, such as otitis media and congenital anomalies. Thus, 53 temporal bones obtained from 41 individuals reported upon here--from 26 weeks' gestation to 8 years of age--will be controls for future studies of pathologic conditions. The children from whom these temporal bones were obtained had no anomalies of the ear (or any other known part of the body); nor did they have any pathologic conditions in the ear. The temporal bones were prepared for histologic study with hematoxylin and eosin staining and were examined under the light microscope. After areas of the mesenchyme in the histologic sections were projected and illustrated for each of 19 portions in the middle ear cleft under the microprojector, those areas were measured by compensating polar planimetry. The findings obtained in this study were as follows: The amount of mesenchyme remaining in the days after birth seemed to gradually decrease in volume with increased maturity and had nearly disappeared within the first year in normal infants. Where mesenchyme was noted in the temporal bones of infants over 1 year of age, it was usually present only in small niches.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108786 TI - The use of metoclopramide in treatment of cisplatin-induced emesis. PMID- 3108787 TI - A head mirror with an integral fiberoptic light source. PMID- 3108788 TI - Central auditory pathology. PMID- 3108789 TI - Treatment of vascular lesions with a CW yellow dye laser--initial trials. AB - Thirteen patients with vascular lesions were treated with a CW yellow dye laser. Most of these patients were either poor candidates for argon laser treatment (ALT) or had undergone unsuccessful argon laser treatment. Twelve patients responded with a "desirable" treatment result. One patient did not respond adequately to have his result classified as "desirable," though all patients experienced fading of their lesions. None of the patients experienced scarring, epidermal thinning, or hypopigmentation. This lack of complications, associated with an incidence of desirable results in twelve of the thirteen patients, is noteworthy because all but one of the patients with portwine stain had difficult to-treat lesions whose treatment is not attempted by many ALT centers. We believe that yellow light has certain advantages over blue-green argon laser light for the treatment of vascular lesions and think that further study is warranted. PMID- 3108790 TI - The endoscopic management of early squamous carcinoma of the vocal cord with the carbon dioxide surgical laser: clinical experience and a proposed subclassification. AB - Sixteen patients with T1 vocal cord squamous cell carcinoma were treated with endoscopic laser excision during a 4-year period. Laser excision was the initial treatment in 11 patients, and it was used to treat 5 patients who had recurrence after radiotherapy. Postoperatively, 13 (81%) of the 16 patients had normal voices. Two patients with persistent postoperative hoarseness had had anterior commissure lesions and previous radiotherapy; the other patient had a subtotal cordectomy. One patient developed a subsequent new lesion 27 months after the initial laser treatment; he was successfully managed with a second endoscopic laser excision. Involvement of the anterior commissure or involvement of the vocal process with minimally invasive disease proved not to be a contraindication to laser excision. The overall results in this small series suggest that laser excision of T1 vocal cord carcinoma is an excellent method of treatment. PMID- 3108791 TI - Real-time monitoring of brainstem auditory evoked response (BAER) during cerebellopontine angle (CPA) surgery. AB - The signal-to-noise ratio of brainstem auditory evoked responses (BAER) can be greatly enhanced by use of optimal digital filtering before averaging. This permits accurate assessment of auditory nerve status every 5 to 10 seconds, making real-time intraoperative monitoring possible. The major advantages yielded by real-time monitoring--in our experience thus far--have been identification of potentially adverse functional consequences of apparently uneventful surgical maneuvers, reducing postoperative dysfunction, early indication of potential for improved clinical function, and potential identification and localization of neural tissue in the face of absent surgical landmarks. Examples of these advantages will be provided from case studies, and the possibility that real-time monitoring may improve ability to preserve hearing will be discussed. PMID- 3108792 TI - The unrecognized rotation of the vestibular and cochlear nerves from the labyrinth to the brain stem: its implications to surgery of the eighth cranial nerve. AB - The cochlear and vestibular nerves rotate 90 degrees from the inner ear to the brain stem. Most of the rotation occurs within the internal auditory canal (IAC); only minimal rotation occurs in the cerebellopontine (CP) angle. At the labyrinthine end of the IAC, the cochlear nerve--which at first lies anterior to the inferior vestibular nerve (saccular nerve)--rapidly fuses with the inferior vestibular nerve. It then rotates to become inferior as the nerves leave the porus acousticus. The cochleovestibular (C-V) cleavage plane lies in a superior inferior direction in the lateral IAC and rotates to become anterior-posterior in the CP angle. In 25% of patients in whom no C-V cleavage plane can be seen, it is not possible to completely transect all vestibular fibers. The surgical implications are that the most complete vestibular neurectomy can be done only in the lateral IAC, the cochlear and inferior vestibular nerves, because of their intimate association, should not be separated in the mid-IAC, in order to prevent damage to the cochlear nerve, and to create a complete denervation of the vestibular labyrinth, only the posterior ampullary nerve along with the superior vestibular nerve should be transected. PMID- 3108793 TI - Should the membranous labyrinth be destroyed because of vertigo? AB - The purpose of this article is to determine if any change has occurred in the role labyrinthectomy plays in the therapeutic armamentarium of members of the American Neurotologic Society. Questionnaires were sent to all members and 42% of these were returned. Analysis of the questionnaires suggests that labyrinthectomy still remains an important tool in the surgical management of vertigo, although it is less frequently employed now than 10 years ago. This seems to be the consequence of increased valuation of even minimal levels of residual hearing. PMID- 3108795 TI - Early and late dilatation for acquired subglottic stenosis. AB - There has been widespread use of periodic dilatations in the management of subglottic stenosis. However, some authorities have questioned the value in the overall rehabilitation of patients affected by this disorder. The first phase of this study included fourteen large dogs in which acute subglottic lesions were created by use of a high-speed electric drill and electrocautery. Twelve animals served as the experimental group and two animals were controls. Obstructing lesions developed in all the animals within 7 to 21 days. When at least a 50% obstruction developed in an animal, a treatment plan was instituted that included at least weekly dilatation, removal of granulations, and administration of intralesional steroids and/or systemic steroids and antibiotics. The two control animals became totally obstructed and were killed. Varying degrees of subglottic stenosis developed in all twelve experimental animals after 8 weeks of dilatation, but none required a tracheotomy. These twelve animals were then subjected to 8 additional weeks of dilatation and antibiotics, and supplemental steroids were used in some animals from this study. It can be concluded that early periodic dilatation and granulation removal in the acutely injured subglottis is effective in prevention of severe stenosis, late periodic dilatations in chronic subglottic stenosis are not helpful in further alleviation of obstruction, the concomitant use of antibiotics and systemic steroids did not appreciably prevent or alter the development of subglottic stenosis, and the concomitant use of intralesional steroids appeared to be of benefit in the management of chronic acquired subglottic stenosis. PMID- 3108794 TI - Antibiotic prophylaxis in high-risk head and neck surgery: one-day vs. five-day therapy. AB - Patients who undergo major contaminated surgery of the head and neck benefit from perioperative antibiotic prophylaxis. This study was developed to determine if 5 days of antibiotic administration would be more effective than 1 day. A multi institutional prospective randomized double-blind study was designed. Patients who were identified as requiring pedicled flap reconstruction were potential candidates for the study. Later, patients were randomly assigned to receive cefoperazone sodium for either 24 hours or 120 hours. In each case, the drug was administered intravenously, beginning 1 to 2 hours preoperatively and continued for the prescribed period. One hundred nine patients were evaluable. Fifty-three patients were assigned to 1 day of perioperative prophylaxis. Wound infection developed in ten patients (18.9%). Fifty-six patients were assigned to 5 days of perioperative antibiotic prophylaxis. Wound infection developed in 14 (25%) of these patients (P greater than .05). These data suggest that no beneficial effect from administration of antibiotics for longer than 24 hours postoperatively can be achieved in patients who undergo myocutaneous flap reconstruction. PMID- 3108796 TI - Primary reconstruction of palatal defects. AB - Removal of the soft palate can cause marked functional deficit in deglutition and phonation. Most commonly, treatment of this deformity with prosthetic obturation has been less than ideal. Numerous reconstructive techniques have met with only partial success, while deforming distant structures. We will present a technique of reconstruction of the soft palate by use of a superiorly based pharyngeal flap. It has been used successfully in five patients who underwent soft palatectomy for malignant disease. The flaps have been the full width of the pharynx and extended down to the esophageal inlet. Viability of the flap is excellent, and the donor site is allowed to heal by secondary intention. Excellent function has been achieved in all cases with no compromise of oncological principles. PMID- 3108797 TI - Immune reactivity in Bell's palsy. AB - Although the pathogenesis of acute facial (Bell's) palsy is probably multifactorial, some investigators believe that the disorder results from autoimmune demyelination and is perhaps related to previous viral infection. The purpose of this study was to identify immune mechanisms which might contribute to Bell's palsy. The lymphocyte transformation test and immunofluorescence were evaluated with a soluble homogenate of unrefined peripheral nerve antigens. Three antigen-nonspecific tests were also studied. Results in 14 patients with Bell's palsy were compared with those in 21 controls. To be eligible for study, patients with Bell's palsy had to be seen within 10 days of onset of weakness. The control group included 5 patients with facial nerve dysfunction from other causes and 16 normal volunteers. No patient or control had previously received steroids. Five patients with Bell's palsy and one normal volunteer had abnormal lymphocyte transformation (p less than .05). Virtually all other tests were normal. These results. suggest that some instances of Bell's palsy result from cell-mediated immunity against peripheral nerve antigens. They also encourage further research in steroid and other immunotherapy. PMID- 3108798 TI - Study of pursuit and vestibulo-ocular cancellation. AB - This present study, a follow-up of our earlier investigation, further examines the time courses of recovery of oculomotor and vestibular function while patients are under the sedative effect of a single dose of secobarbital (Seconal). The assessment included tests for saccade and smooth pursuit, and the vestibulo ocular reflex and its cancellation, as evaluated by sinusoidal and pseudorandom rotation in a high-frequency hydraulic chair (up to 5 Hz). Analysis of results showed that the vestibulo-ocular reflex (VOR) gain, depressed soon after drug intake, recovered substantially after a few hours. Changes in VOR gain were more pronounced with higher frequencies of rotation at 2 and 3 Hz, and greater with pseudorandom than sinusoidal stimulation. Under barbiturate influence, pursuit and VOR cancellation followed distinctly different time courses of recovery. This dissociation between VOR cancellation and pursuit supports the theory that these two systems are subserved by different mechanisms. Saccadic hypermetria was also observed after drug intake. PMID- 3108799 TI - Radiographic imaging of the cochlear implant candidate: preliminary results. AB - Preoperative radiographic imaging of the temporal bone is well accepted in otology for both the diagnosis of disease and the delineation of anatomic structure for surgical planning. Until recently radiographic techniques have unfortunately failed to demonstrate fibrous or bony obstruction of the basal turn of the cochlea, which may cause difficulties during cochlear implantation. Intraoperative findings have been correlated with preoperative imaging in a consecutive group of six cochlear implant recipients and a series of consistent radiographic signs that may indicate the presence of obstruction of the scala tympani have been identified. A classification system has been developed. Based on thin-section high-resolution computerized tomography (HRCT), the system has been used preoperatively on six cochlear implant recipients. In addition, a systematic evaluation of the temporal bone has been developed for precochlear implant evaluation. This includes the thickness of the parietal bone for seating of the receiving device, the degree of pneumatization of the mastoid, the measurement of the size of the facial recess, the description of the size and orientation of the round window niche, and the patency of the basal turn of the cochlea. PMID- 3108800 TI - A technique for the placement of a long-term hyperalimentation catheter in the head and neck oncology patient. AB - The relative safety of silicone rubber catheters allows use of the deep brachial vein for long-term central venous access when other vascular access sites are unavailable or undesirable. After local infiltration, a small incision is made across the medial edge of the brachial biceps and the vein is isolated from the artery and median nerve. An introducer is used to aid in insertion of the catheter. Catheter position is checked with a postoperative radiograph of the chest. Sixty of our patients have had catheters in place from 14 to 200 days, with few complications. There was one catheter-related death from acute bacterial endocarditis and one case of clinical thrombosis. The surgical approach to the deep brachial vein provides a simple and safe method of long-term central venous access in the head and neck oncology patient, whereas regional therapy and treatment planning often preclude use of other more conventional access sites. PMID- 3108801 TI - Photodynamic therapy for head and neck cancer xenografts in athymic mice. AB - This study examines efficacy and optimal treatment variables of photodynamic therapy (PDT) for human head and neck squamous cancer (HNSC) xenografts in athymic mice. Two and four days after injection of hematoporphyrin derivative (HPD), tumors were illuminated with red light from an argon-dye laser. Sixty three tumors were treated. With HPD dose and light intensity constant at 7.5 mg/kg and 100 mW/cm2, respectively, the extent of tumor necrosis was strongly dependent on duration of light exposure. There was no substantial difference in results for 30- and 60-minute treatment durations between animals injected with HPD 2 and 4 days before treatment. After 30 minutes treatment time, responses were seen in 8 of 10 mice (2 days post-HPD) and 11 of 12 mice (4 days post-HPD). After 60 minutes treatment time, toxicity was high. We conclude that, in this model, PDT is effective in selective killing of HNSC. For future comparison studies in this model, if the indicated HPD dose and light intensity are used we recommend a 2-day delay after HPD injection and a light exposure duration of 30 minutes. PMID- 3108802 TI - Collagen grafts--here today and gone tomorrow. AB - The ongoing search for the perfect graft to fill out facial contour defects has frustrated reconstructive surgeons for years. The list of autogenous, homologous, heterologous, and alloplastic materials is extensive. All implantable materials have one or more classical principal drawbacks: shrinkage, extrusion, infection, absorption, and/or deformation. One of the major mechanisms of graft unacceptability is the phenomenon of tissue immunity and graft rejection. This has traditionally been the major disadvantage of homografts and heterografts. The host's immune system recognizes the implant as "non-self," an antibody-antigen reaction is triggered--usually by the antigenic stimulation provided by the proteinaceous component of the graft, and the implant is rejected or destroyed. Conversely, autogenous grafts experience the problem of resorption by the action of macrophages and chronic inflammatory cells. The immunologic sterility of alloplastic grafts is an advantage, but the body often rejects even the most inert materials by the process of chronic inflammation. PMID- 3108803 TI - "Non-otologic" causes for otologic symptoms: two unusual cases. PMID- 3108804 TI - Expression of A9 antigen and loss of blood group antigens as determinants of survival in patients with head and neck squamous carcinoma. AB - The murine monoclonal antibody (A9), raised to the human squamous cell carcinoma (SCC) cell-line UM-SCC-1, defines a squamous cell antigen associated with aggressive biologic behavior of SCC cell lines in vivo and in vitro. In the present investigation, A9 antigen was detected in tissue sections from 37 consecutive, previously untreated patients with SCC of the head and neck. All tumors were positive for A9 binding, although three distinct patterns (reflecting different intensities of A9 expression) were identified. The intensity of A9 expression was independent of primary tumor site, tumor differentiation, keratinization, or growth pattern. The frequency of high expression (Pattern 1) grew with increasing T class, N class, and tumor stage, and was associated with loss of blood group expression in the tumor and with low levels of lymphocyte infiltration in the tumor. Strong A9 expression had a statistically significant association with low nuclear grade (i.e., tumors with more mature and fewer enlarged nuclei, P = 0.019), low vascular/stromal response (i.e., patchy response rather than continuous, P = 0.014), and impaired in vitro lymphokine production by peripheral blood leukocytes (P = 0.0011). Of greatest interest, however, was the strong association of high A9 expression with shortened disease-free interval (DFI) (P = 0.085) and survival (P = 0.081) relative to patients with weak A9 tumor staining (Patterns 2 and 3). Similarly, the loss of blood group antigen expression was strongly associated with decreased DFI (P = 0.038) and survival (P = 0.062). While neither Pattern 1 A9 expression nor loss of blood group reach statistical significance in prediction of survival, the combination of Pattern 1 A9 expression and loss of blood group expression in primary tumors was significantly associated, both with decreased disease-free interval (P = 0.017) and with decreased overall survival (P = 0.011) (median length of follow-up = 22 months). The length of follow-up (LFU) ranged from 2 to 38 months, with a median LFU of 22 months. While the number of patients (37) is small, the significant association between the expression of these cell-surface markers with relapse and survival indicates that immunohistologic staining of the primary tumor will be an important prognostic indicator useful in identification of individual patients at greatest risk of recurrence or early death from head and neck cancer, independent of tumor size, site, or stage at presentation. These markers may thus provide means of selecting patients who should receive adjuvant therapy and more intensive monitoring for the early detection of recurrent disease. PMID- 3108805 TI - Primary adenocarcinoma of the temporal bone mimicking paragangliomas: radiographic and clinical recognition. AB - Three cases of primary adenocarcinoma of the temporal bone which simulated a glomus jugulare tumor (on the basis of a thorough preoperative evaluation) are detailed. In each case, a vascular mass was seen beneath an intact tympanic membrane and angiography revealed the presence of a highly vascular mass centered on the jugular bulb. Computed tomography revealed erosive changes within the jugular fossa that were characteristic of a glomus jugulare tumor; in two cases, a significant posterior fossa extension was documented. The intraoperative findings failed to suggest a lesion different from paraganglioma in two of the cases; in the remaining case, the erosion of both bone and dura was diffuse and more suggestive of a malignant neoplasm. A discussion of the clinical behavior of adenocarcinomas of the middle ear is included in order to emphasize the importance of differentiating these lesions preoperatively from the more commonly encountered paragangliomas. PMID- 3108806 TI - Episodic vertigo in basilar artery migraine. AB - Vestibular symptoms commonly occur in migraine, and episodic vertigo is most frequently seen. Auditory symptoms also occur, but are less common. When Bickerstaff described basilar artery migraine in 1961, he postulated that the many different symptoms were caused by basilar artery ischemia. He documented that neuro-otologic and other symptoms could occur before or during a migraine headache; others later established that these symptoms could also occur during the headache-free period. Case histories of eleven patients with basilar artery migraine are presented in detail. All met the diagnostic criteria for migraine and experienced vertigo before or during episodic headaches--sometimes with other symptoms of transient brainstem dysfunction. Cases represented both typical and unusual manifestations of migraine with vestibular symptoms: four patients were adolescents, three were more than 45 years old and had previously diagnosed migraine headaches, and four were young adults not previously known to have migraine. Many of the patients were thought to have disorders of the vestibular end organ (sometimes in addition to migraine) and three had undergone previous endolymphatic sac decompressions or perilymph fistula repairs. Diagnostic criteria are reviewed, in order that patients with basilar artery migraine can be distinguished from those with peripheral labyrinthine disease, to allow initiation of appropriate antimigraine therapy and avoidance of unnecessary medical and surgical therapy for end-organ disorders. PMID- 3108807 TI - Immunohistochemical detection of retroviral-P15E-related material in carcinomas of the head and neck. AB - As has been reported previously, head and neck carcinomas produce low molecular weight factors (H/N ca LMWFs); a molecular weight less than 25000 daltons is capable of inhibiting the chemotaxis of mononuclear phagocytes. The effect of the factors could be neutralized by antibodies to P15E, one of the structural envelope proteins of Murine Leukemia Viruses (MuLV). This indicates that these low molecular weight factors derived from the tumors are related to P15E. In this study, 35 biopsy specimens of head and neck carcinomas were subjected to an indirect immunoperoxidase assay, in order for P15E-like material to be detected morphologically. All head and neck carcinomas gave positive results. Sixty-three percent of other carcinomas (used as controls) were positive as well. P15E-like material was also expressed in epithelia-overlaying inflammatory responses. Healthy epithelia were not positive. This report thus supports the view that P15E like molecules can be easily detected in cancerous disease--not only by way of biologic isolation, but also by use of immunohistochemical techniques. Since the factor is not specific for the malignant state, it cannot be used as a tumor marker. Possibly involved in the pathogenesis of cancerous disease, its relationship to growth factors, oncogenes, and the immune system needs further clarification. PMID- 3108808 TI - Streptomycin treatment in Meniere's disease. AB - Streptomycin treatment in Meniere's disease has traditionally been used for control of vertigo in patients with severe bilateral involvement or unilateral involvement in the only hearing ear. Guidelines for use that have worked at the Shea Clinic are presented. In addition, a special case is discussed in which this form of therapy has been used for treatment of fluctuant hearing loss in a patient with Meniere's disease. PMID- 3108809 TI - MRI vs. high-resolution CT scanning: evaluation of the anterior skull base. AB - While magnetic resonance imaging (MRI) is no longer a tool of the future, its availability is limited. Most hospitals still use high-resolution computed tomography (CT) scanning as their major imaging modality. Although numerous articles point to the improved diagnostic uses of MRI--as compared to high resolution CT--a change from high-resolution CT scanning to MRI scanning throughout the United States would cost billions of dollars. We should, therefore, delineate those clinical situations in which magnetic resonance imaging is distinctly superior to high-resolution CT scanning. It is already an accepted fact that MRI provides improved imaging of the central nervous system, but, while recent articles maintain the superiority of MRI head and neck imaging, the advantages to the clinician are less clear. We present representative cases of large malignant tumors of the frontal, ethmoid, and sphenoid sinuses, in which the full extent of the disease which involved intracranial structures and the orbit was better defined on the MRI scan than it was on the high-resolution CT scan. Decisions concerning the involvement of the infratemporal fossa, the cavernous sinus, the optic chiasm, the pituitary, and the frontal lobes were more easily made when based upon magnetic resonance imaging, while the tumor involvement as evaluated by CT scanning was much less clear. Establishment of the problem regions of the head and neck--when magnetic resonance imaging is superior to high-resolution CT scanning--will assist in identification of the true need for this tool in the practice of the otolaryngologist--head and neck surgeon. PMID- 3108810 TI - The nasolabial cyst-nasal hamartoma. AB - The nasolabial cyst is an uncommon midfacial cyst. Twenty-six patients with nasolabial cysts were treated at the New York Eye and Ear Infirmary from 1969 to 1986. Most of these lesions manifested facial deformity, unilateral nasal obstruction, and pain when infected. The nasolabial cyst is often unrecognized or confused with other intranasal masses, or fissural and odontogenic cysts. Infection of these lesions--which occurred in 50% of the patients--may mimic facial cellulitis, periodontal abscess, acute maxillary sinusitis, or nasal furuncles. This cyst is considered to be a hamartoma because of its developmental origin from entrapped epithelium in an embryonic fusion plane. Simple aspiration invariably leads to recurrence, and complete surgical excision is the accepted treatment. The nasolabial cyst should be considered in the differential diagnosis of intranasal masses, midface infections, and swelling in the nasolabial area. PMID- 3108811 TI - Reflex control of nasal blood vessels. AB - The effect of stimulation of vagal afferent fibers on nasal blood vessels was studied in 36 cats. Volume change of the nasal capacitance vessels was measured by plethysmographic balloons inserted into the nose. Electrical stimulation of the vagus nerve produced a vasodilatation of nasal mucosa. Pulmonary stretch receptor stimulation by veratridine alkaloid and progressive lung inflation in open-chest cats also produced a vasodilatation of the nasal mucosa. These reflexes were abolished by sectioning the vagus nerves. These results suggest a reflex arc between the lung and nasal capacitance vessels which arises from pulmonary stretch receptors. PMID- 3108812 TI - A technique for intubation of the difficult airway. AB - Intubation of a patient with an obstructive friable tumor mass in the hypopharynx can be difficult. A technique for solving our most difficult cases evolved after all current methods had been tried. This technique combines the use of a tubular laryngoscope and a hollow wand (or guide), through which O2 can be delivered into the trachea as the endotracheal tube is advanced past the obstructing lesion. Existing techniques are also discussed. PMID- 3108813 TI - Analysis of the glycerin test for Meniere's disease. AB - The glycerin test has low sensitivity for Meniere's disease using present published criteria. The purpose of this study is to compare the efficacy of standard empirical criteria with our theoretically based criteria. Subjects were 47 patients with Meniere's disease and 45 patients with other causes of hearing loss and dizziness. Pure-tone thresholds and word-identification scores were determined before and 3 hours after administration of glycerin. The results were submitted to decision and multivariate discriminate analyses. The theoretically based criterion applied to pure-tone threshold testing alone was the most effective protocol for glycerin testing. Combining pure-tone thresholds and word identification increased the false-positive rate without adequately increasing the true-positive rate, and provided no advantage over testing thresholds alone. PMID- 3108814 TI - Laryngeal cysticercosis. PMID- 3108815 TI - Odontogenic myxoma of the maxilla. PMID- 3108816 TI - Facing the hard choices in ethical issues. PMID- 3108818 TI - The prognostic significance of stromal eosinophilia in head and neck cancer. AB - The pathologies of 82 head and neck tumors were examined for histologic features suggestive of poor prognoses. Twelve descriptive histopathologic variables, including two grading scales for malignant tumors, were correlated with DNA flow cytometric data and clinical outcome. We found no correlation between the grading scales and DNA flow cytometric data or clinical outcome. Only one of the histopathologic variables--stromal eosinophilia--was found to significantly correlate with favorable outcome (p = .018). Stromal eosinophilia may be an important new prognostic indicator for head and neck cancer. PMID- 3108819 TI - Accuracy of frozen section diagnosis of the salivary gland. AB - Three hundred and one salivary gland lesions (162 benign, 72 malignant, and 67 benign non-neoplastic) of 677 cases were evaluated by use of intraoperative frozen sections by 66 pathologists. In seven patients, the diagnosis was deferred for permanent sections. In four cases (1.3%), the diagnosis at permanent section changed from one category of benign tumor to another, and in five cases (1.7%), from one category of malignant tumor to another. In four tumors, a frozen section diagnosis of benign was changed to malignant on permanent sectioning; all four involved acinic cell carcinomas. Only two tumors were incorrectly diagnosed as malignant. We conclude that diagnoses of most salivary gland lesions based on frozen section examination are reliable and accurate. However, the literature does indicate that caution should be exercised when malignant tumors are dealt with. PMID- 3108820 TI - Relationship of the optic nerve to the paranasal sinuses as shown by computed tomography. AB - Restricted exposure and inconsistencies in sinus pneumatization place the optic nerve at risk during operations on the sphenoid sinus and posterior ethmoid cells. In this study, computed tomography was used to examine these relationships. We reviewed 80 patients who underwent high-resolution computed tomographic scanning for ophthalmologic complaints in which the scan was negative. Forty-eight percent of posterior ethmoid cells are separated from the optic nerve by the thin bony lamina of the optic canal. Nearly 90% of sphenoid sinuses contact the ipsilateral optic nerve and 10% contact both nerves. Eight percent of posterior ethmoid cells override the ipsilateral sphenoid sinus and contact the optic nerve on that side. Paraxial reformatted displays allowed estimation of the degree of projection of the optic nerve into adjacent sinus cavities. Three percent of optic nerves have significant projection into the posterior ethmoid cell, and 23% project significantly into the sphenoid sinus. The width of the bony plate that separates the optic nerve from the sinus cavity was the same for sphenoid and ethmoid sinuses. Although sinus pneumatization varies among individuals, right and left sides are generally similar within one person. PMID- 3108817 TI - DNA flow cytometry as a prognostic indicator in head and neck cancer. AB - The prognostic significance of deoxyribonucleic acid (DNA) flow cytometry has been investigated for many solid tumors, but few data have been accumulated for squamous cell carcinomas of the head and neck. To our knowledge, we report the largest number of patients (69) with head and neck primary carcinomas to be studied by DNA flow cytometry. In the first part of this study, we reviewed 109 consecutive patients with laryngeal or hypopharyngeal primary carcinomas which were treated at North Carolina Memorial Hospital during the period of 1981 to 1984. The final analysis comprised 139 DNA histograms (mean coefficient of variation: 8.02) on paraffin-embedded specimens from 48 patients. Of the 48 patients with primary carcinomas, 24 had glottic, 18 had supraglottic, and 6 had carcinomas from the piriform sinus. Patients had follow-up for a minimum of 12 months, with a mean follow-up period of 23 months. Twenty-three of the 48 primary carcinomas (48%) were clearly aneuploid, and the remaining 52% were tetraploid (22%) or diploid (30%). We have concluded that patients with clearly aneuploid primary carcinomas had significantly better prognoses than those with diploid tumors (p = 0.008). High DNA amounts (greater than 40% of cells beyond the diploid peak, DNA G1G0) also correlated with a favorable prognosis when compared with low DNA amounts (p less than 0.01), and this remained significant when the clinical outcome was adjusted for staging of the primary site (T), nodal status, and stage of disease. Ploidy was the most significant prognostic variable for the laryngeal group of patients. In the second part of the study, twenty-one patients with oral cavity squamous cell carcinomas were studied in a similar fashion as the group with laryngeal carcinomas. In this group, a low DNA amount, with 40% as the cutoff point, was associated with a favorable prognosis (p = 0.024), and this remained significant while controlling for T, nodal status, and stage of disease. Numbers were too small to permit evaluation of the impact of ploidy in this group, but there was a slight trend toward aneuploidy and tetraploidy, correlating with a poor treatment outcome (p = 0.228). DNA amount was the most significant prognostic variable for the group of patients with oral cavity carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3108821 TI - Surfactant in middle ear effusions. AB - Evidence from animal studies suggests that substances that lower surface tension are present in the middle ear cleft, where they may facilitate opening of the eustachian tube. The purpose of this study was to investigate whether or not surface-tension-lowering substances are present in middle ear effusions. Aspirates from children and adults with secretory otitis media--both serous otitis media and mucoid otitis media--were analyzed by means of two-dimensional thin-layer chromatography. Phospholipids, the major components of pulmonary surfactant, were present in appreciable quantities in all aspirates. Differences in total phosphate content and phospholipid composition were found when effusions from adults and children were compared. PMID- 3108822 TI - Microsphere determination of cochlear blood flow in chickens. AB - Chickens were injected with 9-micron-diameter radioactive microspheres. Cochleas were removed through the external auditory meatus, and the positions of all embedded microspheres were drawn under camera-lucida. Constant measurements of arterial pressures and postinjection blood-gas determinations confirmed that injections were made into normal circulatory systems. The averaged estimate of cochlear blood flow in chickens is 0.75 microliter/min. Variability in these data from chickens is similar to that reported from mammals. A potentially important but puzzling observation is an inverse relationship between blood flow to the cochlea and to the brain. The ease of cochlear extraction makes chickens ideal models for study of cochlear blood flow. PMID- 3108823 TI - Electrical stimulation of the guinea pig cochlea. AB - As a result of practical considerations, histopathologic findings of the temporal bone in humans with cochlear prosthesis implants have been limited. This project attempts to better define safe parameters of electrical stimulation of the inner ear and compare the safe limits of intracochlear vs. extracochlear stimulation sites. Guinea pigs were implanted with single electrodes either on the promontory or in the scala tympani and were stimulated relative to a remote indifferent for 12 hours distributed over a 4-week period. Electrical auditory brainstem evoked responses (EABRs) were tested before and after each of four 3-hour stimulation sessions. Six weeks after implantation, the animals were killed, and their cochleas were examined under the scanning electron microscope. Intracochlear electrodes exhibited thresholds for damage well below one half of that found for most extracochlear stimulation sites. The function-relating damage threshold (in amperes) to frequency of intracochlear stimulation is represented by two straight lines, with an intercept of 1 kHz. The low-frequency limb exhibited a slope of 3 to 4 dB/octave, whereas the high-frequency limb exhibited a slope of 9 to 10 dB/octave. Extracochlear results were too variable to permit speculation. Changes in EABRs were only variably related to histopathologic findings. PMID- 3108824 TI - Immature teratoma of the larynx. AB - Teratomas are unusual tumors which occasionally occur in the head and neck. The tumor consists of the three basic germ-cell layers, in various degrees of maturation. Because of its malignant potential in adults, complete surgical excision is recommended. The patient we have described is believed to provide the first reported case of laryngeal teratoma in the English literature. PMID- 3108825 TI - Hemangiopericytoma of the larynx: a case report and review of the literature. PMID- 3108826 TI - Brain tissue heterotopia in the eighth cranial nerve. PMID- 3108827 TI - [HTLV-III antibodies and immunologic changes in hemophilic children. Prevalence of HTLV-III antibodies in hemophilic children and their relatives living in the same household]. AB - 19 (51%) of 37 hemophiliac children and adolescents regularly treated with factor VIII and IX concentrates were positive for HTLV III antibodies. The prevalence of HTLV III antibodies was higher in patients with severe hemophilia (64%) requiring frequent administration of concentrates than in patients with mild hemophilia (17%). No patient showed signs of AIDS or AIDS related complex. Immunologic alterations (inverse ratio of helper- and suppressor lymphocytes, elevated immunoglobulins, and elevated total serum proteins) were more often observed in patients requiring frequent administration of concentrates than in patients requiring relatively infrequent administration of concentrates. Since in patients frequently treated with concentrates the prevalence of HTLV III antibodies was also higher, it was not possible to draw any conclusions whether the observed immunologic alterations are due to the HTLV III infection alone or are also induced by the frequent administration of coagulation factor concentrates. No HTLV III positive person was detected in 45 relatives of 18 HTLV III positive hemophiliac children living together in 16 households and actively participating in the care of those children. In contrast, 6 (11%) of 55 relatives living in 21 households with 23 hepatitis-B-positive hemophiliac children were positive for hepatitis B. Our results support the general impression, that the risk to contract hepatitis B seems to be greater than to contract HTLV III from seropositive patients, and should help to facilitate the social integration of HTLV III positive hemophiliac children. PMID- 3108828 TI - Scratching behaviour in arthritic rats: a sign of chronic pain or itch? AB - In a previous study, it was shown that adjuvant-induced arthritic rats present an abnormal behaviour pattern up to 60 days after inoculation with Mycobacterium butyricum. The purpose of the present study was to investigate how long the abnormal behaviour pattern continues, and whether the observed increased scratching behaviour is a parameter of chronic pain or rather a reaction to itch. Adjuvant-induced arthritic rats were observed for up to 180 days after the inoculation and their behaviour was quantitatively analysed. The following behavioural changes persisted for more than 60 days: rearing, running and climbing were decreased while grooming, scratching, biting and freezing were increased. No behavioural changes were observed 120 days after the inoculation. The increased scratching was not influenced by an antihistamine drug (astemizole). Not only morphine but also acetylsalicylate selectively depressed the increased scratching behaviour without influencing the other behaviours. These results reinforce the notion that in arthritic rats the increased scratching is a sign of chronic pain. PMID- 3108829 TI - Rapid method for detection of lactose fermenting oral microorganisms. PMID- 3108830 TI - An enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to Encephalitozoon cuniculi and its use in determination of infections in man. AB - An enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies to Encephalitozoon cuniculi in man, using spores derived from tissue culture as antigen. Negligible cross-reactions were found with other microsporidia of vertebrate or of invertebrate origin and there was no cross-reaction with Toxoplasma gondii, using ELISA, immunoperoxidase or immunofluorescence staining. A high prevalence of antibodies to E. cuniculi was found in patients suffering from schistosomiasis, malaria and neurological and psychiatric disorders, but not in healthy individuals. PMID- 3108831 TI - Schistosoma mansoni: structural damage and tegumental repair after in vivo treatment with praziquantel. AB - The long-term, in vivo effects of a single, subcurative dose (200 mg/kg body weight of mouse) of praziquantel on the structure of adult Schistosoma mansoni and on the process and speed of tegumental repair are described. In both male and female worms praziquantel caused often extensive damage to the tegument, in the form of surface blebbings, swellings and lesions, and vacuolization and disruption of the subtegumental tissues. Repair of the drug-induced tegumental damage occurred slowly with partial and, more rarely, complete repair only being seen after 65 days post-treatment (p.t.), although signs of damage were still observed, particularly in male worms, at 100 days p.t. In contrast, repair of damage to the subtegumental/parenchymal tissues including the tegumental perikarya occurred relatively quickly, with the majority of worms examined appearing normal by 8-12 days p.t. The possible role(s) of the host immune response in relation to the speed of tegumental repair in vivo is discussed. PMID- 3108832 TI - Surface antigens of and cross-protection between two geographical isolates of Schistosoma mansoni. AB - Two isolates of Schistosoma mansoni from Puerto Rico and Egypt were examined to determine if there were differences in surface antigens of the schistosomulum and to assess the ability of the two isolates to induce protection against one another in vivo. Immune mouse and human patient antisera recognized the same antigens on the schistosomulum surface of both isolates. However, mice immunized with schistosomula-released products from the Egyptian isolate recognized an additional antigen of Mr 13K on the Egyptian schistosomulum surface which was not present in the Puerto Rican isolate. In quantitative radioimmunoassay, sera from mice vaccinated with irradiated Egyptian cercariae bound more strongly to Egyptian schistosomula than to Puerto Rican parasites. Both isolates cross protected against each other, but mice were less immune to challenge with Egyptian cercariae after being immunized with Puerto Rican irradiated cercariae. There was no difference in immunity to challenge when Egyptian irradiated cercariae were used to immunize. Although this evidence suggested some heterogeneity within the Egyptian isolate, cloned cercariae of the Egyptian isolate did not vary in their ability to cross-protect against each other. Furthermore, antisera from mice immunized with clones of Egyptian cercariae recognized the same schistosomulum surface antigens. The results reported here indicate that although there were small differences between the two isolates the major surface antigens are conserved. PMID- 3108833 TI - Reevaluation of the potential of Fasciola hepatica antigens for immunization against Schistosoma mansoni infection. AB - Previous workers have reported that significant resistance to Schistosoma mansoni cercarial challenge can be induced in mice by immunization with various Fasciola hepatica antigen preparations. We have attempted to reproduce these observations and have also carried out similar experiments in rats. In our hands, however, CBA mice did not develop either antibodies against the schistosomular surface, or significant resistance to challenge after immunization with heterologous antigens. Similar results were obtained in Fischer rats, but rats did develop significant resistance after immunization with homologous (schistosomular) antigens, even without adjuvant, and the homologous 'protective' antigens could be separated by antibody-affinity chromatography using serum from rats vaccinated with irradiated cercariae. Thus, we found no evidence for the existence of shared 'protective' antigens between S. mansoni and F. hepatica, and suggest that this is further evidence that where heterologous resistance can be demonstrated between these two parasites, it is probably due to immunologically non-specific mechanisms. PMID- 3108834 TI - The significance of parasitic infections in terms of clinical disease: a personal view. PMID- 3108835 TI - [Expression of interleukin 2 receptor and class II histocompatibility antigens on lymphocytes of the cerebrospinal fluid in patients with multiple sclerosis and other neurological diseases]. AB - The presence of IL2 receptor and HLA class II antigens on mononuclear cells from both cerebrospinal fluid (CSF) and peripheral blood was examined in patients with multiple sclerosis (MS) and other neurological diseases. Cytofluorographic analysis of mononuclear cells was performed by means of indirect immunofluorescence on a flow cytometer using a linear scale. CSF as compared to blood was enriched in cells expressing IL2 receptor and HLA class II molecules both in MS patients and in other inflammatory diseases of the central nervous system. The site of activation of these cells remains however questionable. PMID- 3108836 TI - [A new molecule in antiparasitic therapy: alpha-difluoromethylornithine]. AB - Alpha-difluoromethylornithine (DFMO) is a specific irreversible inhibitor of ornithine-decarboxylase (ODC), key enzyme in the biosynthesis of polyamines, physiological compounds involved in cell multiplication. Pharmacokinetic studies of the drug revealed good oral absorption, low metabolisation and mainly urinary excretion. Short half-life (3 hrs to 3 hrs 30) implicates daily repeated administrations. DFMO is well tolerated, side effects being reversible on discontinuing drug therapy. They chiefly include diarrheas, hematological perturbations (thrombocytopenia) and hear losses (high dosages). Experimental studies show best results on trypanosomes: curative action in mice infected with Trypanosoma brucei brucei. DFMO is effective too against infection with sporozoites of Plasmodium berghei. Early clinical observations in African patients with Trypanosoma brucei gambiense sleeping sickness show favorable results: efficacy in both stages of the disease, without significant toxicity. Further trials are required to define optimal therapeutic applications. By the way, DFMO already seems to be a promising alternative to conventional therapy of African trypanosomiasis, expecting other indications in the field of antiparasitic chemotherapy. PMID- 3108837 TI - FVIIICag assay on fresh and stored plasma samples using two monoclonal antibodies: an anti FVIIIC and an anti FVIIIR:Ag. PMID- 3108838 TI - Controlled pore glass factor VIII concentrate: influence of heat treatment. AB - A high purity factor VIII concentrate prepared by controlled pore glass (CPG) adsorption chromatography was stabilized with an amino acid mixture, lyophilized and heat treated at 60 degrees C for 72 h. Heat treatment of the freeze-dried concentrate resulted in less than 10% further loss of factor VIII activity, with a final yield of factor VIII from starting plasma of 25%. Heat treatment did not alter product reconstitution, nor appearance, and clinical experience has been favourable. Following infusion into 9 hemophiliac patients the mean ex vivo recovery (1.03) was not significantly different from that obtained with the non heated CPG concentrate. The mean half lives (T1/2) of both heated and non-heat treated material were identical. Stabilization and heat treatment of CPG does not influence the excellent ex vivo recovery, nor therapeutic response, and is not associated with other adverse side effects. PMID- 3108839 TI - Mitomycin C associated hemolytic uremic syndrome. AB - Mitomycin C associated Hemolytic Uremic Syndrome (HUS) is a potentially fatal but uncommon condition that is not yet widely recognised. It consists of microangiopathic hemolytic anemia, thrombocytopenia and progressive renal failure associated with mitomycin C treatment and affects about 10% of patients treated with this agent. The renal failure usually develops about 8-10 mth after start of mitomycin C treatment and the mortality is approximately 60% from renal failure or pulmonary edema. Renal lesions are similar to those seen in idiopathic HUS and include arteriolar fibrin thrombi, expanded subendothelial zones in glomerular capillary walls, ischemic wrinkling of glomerular basement membranes and mesangiolysis. The mechanism of action is postulated as mitomycin C-induced endothelial cell damage. We describe the clinical course and pathological findings in a 65 yr-old man with gastric adenocarcinoma who developed renal failure and thrombocytopenia while on treatment with mitomycin C and died in pulmonary edema. PMID- 3108840 TI - An algorithm for pediatric enteral alimentation. AB - Many of the metabolic and gastrointestinal complications that occur when patients receive tube feedings result from improper selection or administration of the formula. An algorithm, available tables of formula composition, and adequate flowsheets for recording clinical information that can be adapted to individual institutions will provide simple and practical guidelines for the selection, administration, and management of enteral feeding programs in pediatric patients. PMID- 3108841 TI - TPN cholestasis in premature infants: the role of parenteral nutrition solutions. AB - In conclusion, cholestatic liver disease is a frequent complication in low birthweight infants who receive parenteral nutrition. The etiology of this disorder is probably multifactorial. Although the composition of parenteral nutrition solutions may play a role in the development of cholestasis, at this time, there are limited data to suggest how to change parenteral solutions to alter the course of this disease. Further work is necessary to elucidate therapies to prevent and treat this disorder. PMID- 3108842 TI - Ventilatory response to inspired carbon dioxide in premature infants recovering from intraventricular hemorrhage. AB - We examined the ventilatory response to inhaled carbon dioxide with a computerized waveform analyzer in two groups of premature infants. Twenty-seven infants suffered from periventricular-intraventricular hemorrhage (IVH) during the first week of life and comprised the study group (birth weight 1.2 +/- 0.2 kg, gestational age 29 +/- 2 weeks). The control group consisted of 15 infants without IVH (birth weight 1.4 +/- 0.3 kg, gestational age 30 +/- 2 weeks). Study infants were evaluated at a postnatal age of 9 +/- 2 weeks and control infants at 7 +/- 3 weeks. No differences were found in the slope or position of the ventilatory response curve, baseline PACO2, increase in minute ventilation, VT/Ttot, and Ti/Ttot between the two groups. Subgroups with unresolved apnea (10 IVH and eight control infants) demonstrated a rightward shift of the ventilatory response curve compared to those infants without apnea. A previous IVH did not reduce the ventilatory response to CO2 in this group of infants. PMID- 3108844 TI - Abdominal colic due to ureteric diverticulum with stone formation. AB - In a 15-year-old boy right lower abdominal colicky pain was caused by intermittent obstruction of the ureter by stones which had accumulated in a ureteric diverticulum. As was shown by repeated X-rays, each of these stones had moved to the ureter and back to the diverticulum. Ureteric diverticulum mostly remains asymptomatic in children: stone formation and obstruction of the ureter by the stones is one of the instances which may cause symptoms. PMID- 3108843 TI - Vasodilatory effect of aerosol histamine during pulmonary vasoconstriction in unanesthetized sheep. AB - The effects of aerosol histamine on pulmonary vascular resistance during pulmonary vasoconstriction were studied in 12 unanesthetized sheep. Sheep were chronically instrumental with Silastic catheters in the pulmonary artery and left atrium, thermodilution Swan-Ganz catheter in the main pulmonary artery for measurement of cardiac output, and tracheostomy for delivery of hypoxic gas and/or aerosol histamine. Seven minutes of isocapnic hypoxia (FIO2 = 0.12) caused pulmonary artery pressure (PPA) to increase from 17.2 +/- 0.4 to 27.0 +/- 1.0 cm H2O (mean +/- SEM, P less than 0.05) and pulmonary vascular resistance (PVR) to increase from 3.94 +/- 0.33 to 4.71 +/- 0.38 cm H2O x L-1 x min (P less than 0.05). When sheep breathed a combination of aerosol histamine (5 mg/ml) and 12% O2, PPA rose only 21.3 +/- 1.11 cm H2O and PVR decreased to 3.51 +/- 0.31 cm H2O x L-1 x min. This was a significantly (P less than 0.05) smaller response compared to hypoxia alone. Aerosol histamine alone had to significant effect on PPA or PVR. Meclofenamate did not restore the histamine-induced loss of hypoxic vasoconstriction. Aerosol histamine significantly blunted the pulmonary vasoconstriction caused by intravenous serotonin (8 micrograms/kg/min) and intravenous prostaglandin H2-analog (0.74 microgram/kg/min). It was concluded that in the awake sheep aerosol histamine acted as a pulmonary vasodilator only in the presence of pulmonary vasoconstriction. PMID- 3108845 TI - Passage of the first stool in very low birth weight infants. AB - Times of first stool passage were studied in 171 infants who weighed less than 1,500 g at birth. Delayed passage (greater than 48 hours) was noted in 20.4% of this group. Significant differences were noted between the delayed and nondelayed groups for gestational age, presence of severe respiratory distress syndrome, and the time of the first enteral feeding. In very low birth weight infants, delay in the passage of the first stool is a common occurrence. This delay is probably due to physiologic immaturity of the motor mechanisms of the gut, lack of triggering effect of enteral feeds on gut hormones, and the presence of severe respiratory distress syndrome, which may singly or in concert adversely affect gastrointestinal motility. PMID- 3108846 TI - Frequency and cost of diagnosis-related group outliers among newborns. AB - Analysis of outliers, as defined by the Health Care Financing Administration, among 47,776 newborns discharged from 33 short-term hospitals in Maryland in 1981 shows that the three prematurity diagnosis-related groups (DRGs) (386 to 388) represented only 5.3% of all discharges of newborns, but more than one fifth of all outliers and more than three fifths of outlier days of care for newborns. The disparity in charges for outliers and inliers (not exceeding the "trim point") is even more dramatic. Newborns with "extreme immaturity" (DRG 386) and "prematurity with major problems" (DRG 387) together accounted for less than 3% of all newborn discharges but for nearly one fourth of all outlier discharges. The mean length of stay in hospitals for outliers in those two DRGs was more than 2 months. The mean charge per outlier discharge in DRG 386 was $27,061 in 1981. Nearly one third of the discharges and more than two thirds of the days of care in this DRG were for outliers. Outliers occurred up to five times more often among premature neonates than among normal newborns and occurred preponderantly in teaching hospitals, especially those with more than 400 beds. This finding may require a reevaluation of the outlier trim points and the reimbursement method for newborn DRGs to assure adequate payment to the providers of neonatal intensive care, mainly large teaching hospitals. PMID- 3108847 TI - Persistently low blood retinol levels during and after parenteral feeding of very low birth weight infants: examination of losses into intravenous administration sets and a method of prevention by addition to a lipid emulsion. AB - Very low birth weight infants have little storage of hepatic retinol and are, therefore, highly dependent upon an exogenous supply. The recent association between low serum retinol level and bronchopulmonary dysplasia and the persistently low serum levels of retinol during total parenteral nutrition prompted a prospective study to evaluate serial changes in serum retinol levels during 1 month of total parenteral nutrition (retinol dose 455 micrograms/d) and again during 1 month of total enteral feeding (retinol dose 200 to 300 micrograms/d) in the same infants. Infants were divided into two groups. Group 1 consisted of infants weighing less than 1,000 g (n = 24) and group 2 consisted of infants weighing 1,000 to 1,500 g (n = 17). Although initial mean levels of retinol were similar in both groups (14.8 +/- 0.9 and 13.5 +/- 0.7 micrograms/dL), there was wide variation between infants. In group 1 infants, there was a significant (P less than .01) decline in retinol level by the second week of life (to 9.2 +/- 1 micrograms/dL), which persisted during total parenteral nutrition, but increased to 13.4 +/- 2 after 1 week of enteral feeding. This level was maintained throughout enteral feeding. In group 2 infants, there was no significant change in serum retinol level throughout the study. During total parenteral nutrition, several infants had retinol levels below 10 micrograms/dL, a level associated with signs of retinol deficiency in older children. Because losses of retinol are known to occur in smaller volume total parenteral nutrition solutions, it was speculated that losses of retinol in our patients were due to retinol losses in the total parenteral nutrition delivery system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108848 TI - Kasabach-Merritt syndrome: therapeutic considerations. AB - During the past 15 years we have managed six children with capillary hemangiomas in association with consumptive coagulopathy--the Kasabach-Merritt syndrome. Their ages when first seen ranged from 2 weeks to 4 years with a mean of 19 months. In three of the patients, the hemangiomas remained small for many months and then suddenly enlarged and hemorrhagic diatheses appeared. The duration of the thrombocytopenia ranged from 5 to 20 months, a time span that in some of the patients was influenced by the type of treatment used. Each patient received a variety of therapies including the following: medications to control the coagulopathy; mechanical, cytolytic, and pharmacologic treatment to eradicate the lesion; and blood product support with platelets and cryoprecipitate for severe bleeding. A prompt elevation of the platelet count occurred in three of the patients after the lesion was biopsied. Subtotal resection of the lesion resulted in an immediate increase of the platelet count in one patient. A transient increase in platelet counts and fibrinogen levels was observed in another patient following several embolizations of a portion of the hemangioma. Other modes of therapy were difficult to evaluate, especially because the same therapy applied at different times in the same patient effected a different type of response. Eventually, all of the patients experienced resolution of their lesions and, with this, concomitant reversal of the coagulopathy. PMID- 3108849 TI - Interruption of pregnancy by cervical rivanol predilatation. AB - Experience obtained in 1361 cases of first trimester pregnancy interruption with cervical Rivanol predilatation is reported. Rivanol-induced predilatation of the cervical canal prior to interruption was found to be an efficient procedure. The dilating effect of Rivanol could not be enhanced by i.m. administration of 5 IU oxytocin. After the interruption of more advanced pregnancies a higher degree of dilatation of the cervix was observed. The necessity of further dilatation prior to vacuum aspiration is, in the majority of cases, not higher than 2-2.5 H, which is insignificant on the softened cervix. The immediate complications of medical induction and interruption were infrequent and not severe. Thus, cervical predilatation with Rivanol prior to vacuum aspiration is a recommendable method of pregnancy interruption, worthy of widespread application. PMID- 3108850 TI - Early complications of first trimester interruption of pregnancies with rivanol predilatation. AB - The early complications of the non-invasive interruption of 1361 first trimester pregnancies induced by Rivanol predilatation were studied. For this purpose the patients were called back for follow-up examination 6 weeks after the operation. The number of patients reporting at the control examination was 769. The number of febrile complications of genital origin was low. Slight postoperative bleeding exceeded the amount of normal menstruation only in 4.9% of the patients and, in general, it did not last longer than 7 days. The same applied to abdominal and lumbar complaints. The proportion of early complications was lower than after interruptions with the D + VA and D + C methods. The first menstruation after the operation did not differ from the earlier menstruation pattern of the particular patient in 75.9% of the cases. This also showed that the use of Rivanol did not involve lasting and severe damage to the endometrium. PMID- 3108851 TI - Examination of gestations and deliveries subsequent to rivanol-induced interruption of first trimester pregnancies. AB - The pregnancies and deliveries of 550 parturient women were studied. The women previously had undergone interruption of pregnancy induced by Rivanol predilatation of the cervical canal. As controls served the data of 557 pregnancies and deliveries in which the pregnant women had formerly undergone invasive interruption of pregnancy. In addition the data of further 531 women were studied whose last delivery occurred before term or of a small for dates baby. The examinations showed that the necessitating cerclage occurrence of cervical incompetence was significantly lower in pregnancies following non invasive interruption than after those following invasive interruption. There were no differences in the start and course of delivery and in the number of complications that could be traced back to the method of interruption. There was no difference in the intactness, site of adherence, separation and gross structure of the placenta. The condition of neonates at delivery was similar in the two groups. On the other hand, in the group of invasive interruptions the proportion of neonates that needed medical treatment was higher. An important observation was that after non-invasive interruption the proportion of preterm and small for dates births was significantly lower. These findings may be important in everyday practice. PMID- 3108852 TI - [Prevention of perinatal viral hepatitis A, B, and non-A, non-B]. PMID- 3108853 TI - Intracellular pH and buffer power of type 1 and 2 fibres from skeletal muscle of Xenopus laevis. AB - Intracellular pH (pHi) and buffering power of type 1 and type 2 fibres from the iliofibularis muscle of the clawed frog, Xenopus laevis, have been measured using pH-sensitive microelectrodes. In phosphate buffered Ringer's solution (extracellular pH 7.25, 20-22 degrees C), mean pHi and its variance were similar in the two fibre types (6.86 +/- SD 0.15 +/- SEM 0.03, n = 24, type 1, and 6.86 +/- SD 0.12 +/- SEM 0.03, n = 15, type 2). On changing to Ringer's solution containing CO2 and HCO3- (extracellular pH 7.25, 20-22 degrees C), pHi became more acid in both fibre types. Although H+ ions were not at electrochemical equilibrium across the surface membrane, active transport did not return pHi to its original value during exposure to CO2. The buffering powers calculated from the changes in pHi were not significantly different, 41.6 mmol X l-1 per pH unit (+/- SEM 4.0, n = 17) for type 1 and 49.3 mmol X l per pH unit (+/- SEM 7.2, n = 11) for type 2 fibres. Thus differences in the mechanical properties of these fibre types are not due simply to a difference of the intracellular pH or buffering of resting fibres. Other possible explanations are discussed for the changes in some contractile properties that occur when pHi is acidified. PMID- 3108854 TI - The white gene as a marker in a new P-element vector for gene transfer in Drosophila. AB - We describe new vectors suitable for P-element mediated germ line transformation of Drosophila melanogaster using passenger genes whose expression does not result in a readily detectable phenotypic change of the transformed flies. The P-element vectors contain the white gene fused to the heat shock protein 70 (hsp70) gene promoter. Expression of the white gene rescues the white phenotype of recipient flies partly or completely even without heat treatment. Transformed descendents of most founder animals (GO) fall into two classes which are distinguishable by their orange and red eye colours. The different levels of white expression are presumably due to position effects associated with different chromosomal sites of insertion. Doubling of the gene dose in orange eyed fly stocks results in an easily visible darkening of the eye colour. Consequently, the generation of homozygous transformants is easily possible by simple inbreeding due to the phenotypic distinction of homo- and heterozygous transformants. Cloning into these P-element vectors is facilitated by the presence of polylinkers with 8 and 12 unique restriction sites. PMID- 3108857 TI - Nucleotide sequence of human liver carbonic anhydrase II cDNA. PMID- 3108856 TI - Regulation of differential processing of mouse immunoglobulin mu heavy-chain mRNA. AB - The switch between the synthesis of membrane-bound and secreted IgM during B cell differentiation is accomplished by producing, from a single gene, two alternative forms of mu heavy-chain mRNA that differ only in their 3' termini. The precursor mu RNA is either polyadenylated at the first poly(A) site, for secreted mu mRNA, or spliced between the C4 and M1 exons, for membrane-bound mu mRNA, in a mutually exclusive manner. To elucidate the molecular mechanism of the differential processing of mouse mu mRNA, we analyzed the expression of various mouse mu gene constructs stably transfected into mouse cell lines. In B cell lines, processing of the exogenously transfected mu gene transcripts accurately reflected the developmental stage of the recipient cells: both secreted and membrane-bound mu mRNAs are produced in early-stage B cells while secreted mu mRNA is primarily produced in late-stage B cells. In fibroblast cell lines, mu mRNAs transcribed from the Moloney murine sarcoma virus LTR promoter were processed primarily to the secreted form. Thus, production of the secreted form seems to be the non regulated processing pattern. When the splicing signal of the C4-M1 intron was mutagenized, polyadenylation at the first poly(A) site occurred efficiently regardless of the recipient cell lines. On the other hand, when the polyadenylation signal was mutagenized, the splicing occurred efficiently in early-stage B cells, but only weakly in late-stage B cells and fibroblast cells. These results suggest that the splicing of the C4-M1 intron is stimulated in early-stage B cells. PMID- 3108858 TI - Short gene inversion involving two adjacent heavy chain joining minigenes and one heavy chain diversity minigene in the nonsecretor Sp2/0-Ag14 myeloma cell line. PMID- 3108855 TI - Pseudomonas aeruginosa infection in cystic fibrosis: nucleotide sequence and transcriptional regulation of the algD gene. AB - Pulmonary infection by mucoid, alginate producing, Pseudomonas aeruginosa is a major complication in patients suffering from cystic fibrosis (CF). To analyze the mechanisms leading to the emergence of mucoid P. aeruginosa in CF lungs, control of the algD gene coding for GDPmannose dehydrogenase was studied. Transcriptional activation of algD was shown to be necessary for alginate production. Sequencing of algD and its promoter revealed multiple direct repeats upstream of the transcription start and throughout the promoter region. Using the algD-xy1E transcriptional fusion the algD promoter was demonstrated to be under positive control by the algR gene. This gene has previously been shown to undergo antibiotic promoted chromosomal amplification resulting in the emergence of the mucoid phenotype. These findings provide a basis for better understanding the control of mucoidy in P. aeruginosa. PMID- 3108859 TI - Bacillus subtilis phage SPR codes for a DNA methyltransferase with triple sequence specificity. AB - SPR, a temperate Bacillus subtilis phage, codes for a DNA methyltransferase that can methylate the sequences GGCC (or GGCC) and CCGG at the cytosines indicated. We show here that it can also methylate the sequence CC(A/T)GG and protect it from cleavage with EcoRII and ApyI. This methylation can be seen in vivo as well as in vitro with purified SPR methyltransferase. SPR19 and SPR83 are two mutant phages, defective in GGCC or CCGG methylation, respectively. These mutants have not lost their ability to methylate CC(A/T)GG sites. Mutation SPR26 has lost the ability to methylate all three sites. Thus the SPR methyltransferase codes for three genetically distinguishable methylation abilities. PMID- 3108860 TI - Deletion analysis of a unique 3' splice site indicates that alternating guanine and thymine residues represent an efficient splicing signal. AB - The 3' splice site of the second intron (I2) of the human apolipoprotein-AII gene, (GT)16GGGCAG, is unique in that, although fully functional, a stretch of alternating guanine and thymine residues replaces the polypyrimidine tract usually associated with 3' splice junctions. The transient expression of successive 5' deletion mutants has defined the minimum number of nucleotides at the 3' end of apo-AII I2 that are required to direct efficient splicing. Processing in two cell-types, representing apo-AII producing and non-producing tissue was identical; in both, only by removing all the GT repeats did the 3' splice site of apo-AII I2 become completely non-functional. Similar deletion analyses of "classic" 3' splice sites, which conform to the consensus sequence (Y)nNYAG, have indicated that a minimum of 14 nucleotides of the polypyrimidine tract are required for detectable levels of processing to take place. Here we report that the six nucleotides (GT)2GG, which directly replace this tract in a deletion mutant of the 3' splice site of apo-AII I2 are sufficient to direct the splicing process efficiently and correctly. PMID- 3108862 TI - Nucleotide sequence of the Euglena gracilis chloroplast gene for ribosomal protein L20. PMID- 3108861 TI - Expression of the lacZ gene from two methanol-regulated promoters in Pichia pastoris. AB - Two DNA fragments containing putative control regions regulating the expression of the alcohol oxidase (AOX) and dihydroxy-acetone synthase (DAS) genes from the methylotrophic yeast Pichia pastoris were used in the construction of vectors for the expression of the Escherichia coli lacZ gene. These vectors were transformed into P. pastoris host cells and employed in experiments to measure the control mechanisms employed by each promoter in the production of beta-galactosidase fusion products. Results in P. pastoris suggest that the processes used to regulate the expression of these gene fusions involve both repression/derepression and induction mechanisms. Expression of the AOX-lacZ and DAS-lacZ fusions was examined in Saccharomyces cerevisiae as well. Interestingly, beta-galactosidase was expressed in a regulated manner in the heterologous host. PMID- 3108863 TI - Adhn4 of Drosophila melanogaster is a nonsense mutation. PMID- 3108864 TI - Nucleotide and deduced amino acid sequence of rat liver 17 beta-hydroxysteroid UDP-glucuronosyltransferase. PMID- 3108865 TI - Spinal cord immunoreactive TRH is altered after local traumatic injury. AB - The effect of impaction-induced spinal trauma on the concentration of immunoreactive TRH (TRH-ir) in the spinal cord was studied. Samples were obtained from tissues proximal to, distal to, and at the site of injury at 30 min, 1 hr, 4 hr, and 6 weeks after impaction. After an initial 38% depletion of TRH-ir at the injury site at 30 min, concentrations were progressively elevated over time at all sites. These elevations reached statistical significance in the proximal and distal segments by 4 hr posttrauma. By 6 weeks, a rostral-caudal gradient of TRH ir concentration was observed, indicating that axoplasmic transport was restricted. The gradient was characterized by a significant TRH-ir elevation proximal to, and a 60% depletion distal to, the injury. The short-term TRH-ir elevation measured indicates that the ability of exogenously administered TRH to reduce the incidence of posttraumatic functional deficit stems from a restoration of endogenous TRH action. The role of the raphe-spinal tract in the development of traumatic paralysis is considered. PMID- 3108866 TI - Regional distribution of in vitro release of thyrotropin releasing hormone in rat brain. AB - To increase our knowledge of the TRH functions in brain and the processes of TRH compartmentalization and release, we studied the in vitro release of endogenous TRH in different brain areas. We also determined the correlation between TRH levels and release under both basal and stimulated conditions. TRH concentration was measured in tissues and media by specific radioimmunoassay. TRH-like material detected in olfactory bulb and hypothalamic incubates (basal or K+ stimulated) were shown to be chromatographically identical to synthetic TRH. Different brain regions showed high variability in the basal release of TRH (1-20% of tissue content). This suggests the existence of different pools. The response to depolarizing stimulus (56 mM K+) was significant only in the following regions: median eminence, total hypothalamus, preoptic area, nucleus accumbens-lateral septum, amygdala, mesencephalon, medulla oblongata and the cervical region of the spinal cord. These regions have been shown to contain a high number of receptors, a high concentration of TRH nerve endings and are susceptible to TRH effects. These results support the hypothesis that TRH functions as neuromodulator in these areas. PMID- 3108867 TI - Neuromodulatory effects of TRH upon swim and cholinergic analgesia. AB - In addition to short-acting analgesic actions by itself and modulation of analgesic responses induced by endogenous opioids and neurotensin, central administration of thyrotropin-releasing hormone (TRH) potentiates footshock analgesia. The present study evaluated the effects of TRH upon the neurohormonally-mediated though nonopioid analgesia induced by swims in rats. Intracerebroventricular TRH (10 and 50 micrograms) dose-dependently potentiated swim (21, 15, 2 degrees C baths) analgesia on the tail-flick test, an effect which was not due to the hypothermic or basal pain threshold changes. Intravenous (8 mg/kg) TRH potentiated swim (21 degrees C) analgesia; the 600:1 difference in potency between routes strongly suggests central sites of neuromodulatory action. Intracerebroventricular diketopiperazine (50 micrograms), a TRH metabolite, and RX77368 (50 micrograms), a TRH analogue, also potentiated swim (21 degrees C) analgesia, effects also independent of hypothermia and basal reactivity to pain. Finally, given the excitatory interaction between TRH and acetylcholine as well as the cholinergic involvement in swim analgesia, intracerebroventricular TRH potentiated pilocarpine (10 mg/kg, IP) analgesia. PMID- 3108868 TI - Primary prevention of coronary heart disease: a review of multifactor prevention trials. PMID- 3108869 TI - [Results of using a polyvalent vaccine against Pseudomonas aeruginosa in patients with burns treated at various therapeutic centers in Poland]. PMID- 3108870 TI - [Various problems in relation to the feeding of severely burned patients]. PMID- 3108871 TI - What are we supposed to do with them? PMID- 3108872 TI - Distribution of Microcystis aeruginosa peptide toxin and interactions with hepatic microsomes in mice. AB - Purified 14C-labelled peptide toxin from the cyanobacterium Microcystis aeruginosa was administered intraperitoneally to mice and the distribution of label determined between the major organs. Seventy per cent of the label was localized in the liver after 1 min.; this value increasing to almost 90 per cent after 3 hours. Label associated with the lungs and other individual organs varied between 10 and 1 per cent of the 14C recovered throughout. Three microsomal enzyme inducers, beta-naphthoflavone, 3-methylcholanthrene and phenobarbital, afforded protection against liver damage and extended survival if given to mice before the administration of an LD50 dose of toxin. Toxin-dependent changes in liver cytochrome levels were also reduced by the enzyme inducers. PMID- 3108873 TI - Biochemical and morphological changes induced by sodium valproate in rat liver. PMID- 3108874 TI - Valpromide but not sodium hydrogen divalproate inhibits epoxide hydrolase in human liver. PMID- 3108875 TI - S-adenosylmethionine and transmethylation reactions in trichomonads. AB - S-Adenosylmethionine (SAM) levels in trichomonads, a range of trypanosomatids and mouse liver were measured using HPLC techniques. The concentrations were found to be similar in each with the exception of Herpetomonas muscarum ingenoplastis, which contained approximately ten-fold more. Living trichomonads were found to incorporate exogenous L-methionine into intracellular SAM and its methyl carbon was also detected in lipids and nucleic acids, presumably through its involvement in transmethylation reactions. Norleucine and cycloleucine inhibited L-methionine uptake and incorporation into living Trichomonas vaginalis. Both the rates of incorporation of exogenous L-methionine into intracellular SAM and its involvement in transmethylation reactions were greater for Trichomonas vaginalis than for Tritrichomonas foetus. The results suggest that Trichomonas vaginalis and other trichomonads contain enzymes equivalent to SAM synthetase (EC 2.5.1.6) and SAM-dependent methyltransferases (EC 2.1.1). PMID- 3108876 TI - Stimulation of phospholipase A2 activity in bovine rod outer segments by the beta gamma subunits of transducin and its inhibition by the alpha subunit. AB - In the rod outer segments (ROS) of bovine retina, light activation of phospholipase A2 has been shown to occur by a transducin-dependent mechanism. In this report, the transducin-mediated stimulation of phospholipase A2 is shown to require dissociation of the alpha beta gamma heterotrimer. Addition of transducin to dark-adapted transducin-poor ROS stimulated phospholipase A2 activity only with coincident exposure to white light or, in the dark, with addition of the hydrolysis-resistant GTP analog, guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]). Both light and GTP[gamma-S] induced dissociation of the transducin subunits and led to severalfold increases in the phospholipase A2 activity of transducin rich, but not transducin-poor, ROS. In contrast, pertussis toxin treatment of transducin, which stabilizes the associated state of this G protein, prevented the stimulation of phospholipase A2 by exogenous transducin in the presence of light. Addition of purified transducin subunits to dark-adapted transducin-poor ROS revealed that phospholipase A2 stimulation occurred by action of the beta gamma subunits. This is in contrast to the transducin-mediated increase in cGMP phosphodiesterase activity, where activation occurs by action of the alpha subunit. The alpha subunit, which itself slightly stimulated phospholipase A2 activity, inhibited the beta gamma-induced stimulation of phospholipase A2. This inhibition appears to be the result of subunit reassociation since addition of GTP[gamma-S] abolished the inhibitory effect of the alpha subunit on the beta gamma-induced increase in phospholipase A2, while pertussis toxin treatment of the subunits further inhibited phospholipase A2 activity. Modulation of phospholipase A2 activity by the transducin subunit is, therefore, a mode of action for these subunits in signal transduction. PMID- 3108877 TI - Rapid enhancement of beta 2-interferon/B-cell differentiation factor BSF-2 gene expression in human fibroblasts by diacylglycerols and the calcium ionophore A23187. AB - The expression in human fibroblasts of the beta 2-interferon (IFN-beta 2) gene, which is now recognized to be identical to the gene encoding B-cell differentiation factor BSF-2, is enhanced by several cytokines that affect cell growth (tumor necrosis factor, interleukin 1, platelet-derived growth factor, and beta 1-interferon). We have examined the possibility that IFN-beta 2 gene expression is regulated through activation, by diacylglycerol, of the protein kinase C pathway. The synthetic diacylglycerols 1,2-dioctanoylglycerol (diC8) and 1-oleoyl-2-acetylglycerol strongly enhanced IFN-beta 2, but not IFN-beta 1, gene expression in human fibroblasts (FS-4 strain). An increase in IFN-beta 2 mRNA level was detected within 15 min after addition of diC8 (290 microM) to FS-4 cells and was maximal approximately 20 hr later. An increase in IFN-beta 2 gene transcription was detected within 5 min of addition of diC8, and the rate of transcription was near-maximal by 15-30 min. The enhancement of IFN-beta 2 gene expression by diC8, interleukin 1, or tumor necrosis factor was not prevented by H8, a preferential inhibitor of cAMP- and cGMP-dependent protein kinases, but was blocked by H7, an inhibitor of protein kinase C as well as of cyclic nucleotide dependent protein kinases. diC8 was found to protect FS-4 cells from the cytopathic effect of vesicular stomatitis virus; this protection was blocked by polyclonal or monoclonal antibodies that neutralize IFN-beta, suggesting that the antiviral effect was due to the secretion of IFN-beta 2 by the diC8-treated fibroblasts. The calcium ionophore A23187 (1-10 microM) also elicited an increase in the level of IFN-beta 2 mRNA in FS-4 fibroblasts; appropriate combinations of A23187 and diC8 had at least an additive effect in enhancing IFN-beta 2 mRNA levels. These results show that protein kinase C-activating or [Ca2+]-elevating agents rapidly increase the expression of the IFN-beta 2 gene in human fibroblasts. PMID- 3108878 TI - Kinds of mutations formed when a shuttle vector containing adducts of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9, 10 tetrahydrobenzo[a]pyrene replicates in human cells. AB - We have investigated the kinds of mutations induced when a shuttle vector containing covalently bound residues of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (BPDE) replicates in human cells. A human embryonic kidney cell line, 293, was used as the eukaryotic host. The target gene for mutation analysis, supF, codes for a tyrosine suppressor tRNA and is strategically located between the origin of replication of the plasmid in Escherichia coli and the gene for a selectable marker, so that the possibility of recovering supF mutants containing gross rearrangements is low. The frequency of supF mutants obtained when untreated plasmid replicated in 293 cells was 1.4 X 10(-4). The frequency with BPDE-treated plasmid increased linearly as a function of the number of adducts, with 16 adducts per plasmid giving 38 X 10(-4). Polyacrylamide gel and agarose gel electrophoresis analysis of 137 plasmids with mutations in the supF gene indicated that 70% (21/30) from untreated plasmids contained deletions or insertions or showed altered gel mobility, whereas only 28% (30/107) of those derived from BPDE-treated plasmids contained such alterations. Of the 86 unequivocally independent mutants derived from BPDE treated plasmids that were analyzed by sequencing, the majority (60/86) exhibited base substitutions. Mutants exhibiting frameshifts (insertions or deletions of one, two, or four base pairs) were also found, but they were a minority (11/86). In the progeny of BPDE-treated plasmids 61/71 base substitutions observed were transversions, with 45/61 G X C----T X A. Examination of the location of BPDE induced mutations among the 85 base pairs in the structure of the tRNA revealed that 30% of the base substitutions occurred at two sites and 44% of the rest occurred at five other hot spots. Only 20% of all these base changes involved a site in which a guanine containing a BPDE adduct is predicted to be labile--i.e., a guanine that has a pyrimidine to its 5' side. PMID- 3108879 TI - Distinct forms of the beta subunit of GTP-binding regulatory proteins identified by molecular cloning. AB - Two distinct beta subunits of guanine nucleotide-binding regulatory proteins have been identified by cDNA cloning and are referred to as beta 1 and beta 2 subunits. The bovine transducin beta subunit (beta 1) has been cloned previously. We have now isolated and analyzed cDNA clones that encode the beta 2 subunit from bovine adrenal, bovine brain, and a human myeloid leukemia cell line, HL-60. The 340-residue Mr 37,329 beta 2 protein is 90% identical with beta 1 in predicted amino acid sequence, and it is also organized as a series of repetitive homologous segments. The major mRNA that encodes the bovine beta 2 subunit is 1.7 kilobases in length. It is expressed at lower levels than beta 1 subunit mRNA in all tissues examined. The beta 1 and beta 2 messages are expressed in cloned human cell lines. Hybridization of cDNA probes to bovine DNA showed that beta 1 and beta 2 are encoded by separate genes. The amino acid sequences for the bovine and human beta 2 subunit are identical, as are the amino acid sequences for the bovine and human beta 1 subunit. This evolutionary conservation suggests that the two beta subunits have different roles in the signal transduction process. PMID- 3108881 TI - Assessment of antigen-specific receptor function of surface immunoglobulin M and D with identical hapten specificity. AB - Monoclonal B-cell lines expressing antigen-specific surface IgM or IgD were established by transferring the genes encoding immunoglobulin heavy (mu or delta) and light (kappa) chains specific for the hapten 2,4,6-trinitrophenyl (TNP) into a B-cell lymphoma line. Two IgMTNP and two IgDTNP transformants were selected on the basis of similar levels of anti-TNP idiotype expression by flow microfluorimetric analysis. The IgMTNP and IgDTNP transformants were compared in quantitative assays for their ability to bind TNP-carrier and present TNP-carrier to carrier-specific T cells. Our results indicate that IgMTNP and IgDTNP transformants have an equal capacity to bind and present specific antigen. Thus surface IgM and IgD, when present in equivalent amounts, function similarly as antigen receptors. PMID- 3108880 TI - T3 glycoprotein is functional although structurally distinct on human T-cell receptor gamma T lymphocytes. AB - The T-cell receptor (TCR) gamma gene product occurs in association with T3 (CD3) polypeptides on the surface of human T lymphocytes. TCR gamma lymphocytes express arrays of T3 polypeptides distinct from those typically observed on TCR alpha beta lymphocytes. This report demonstrates that identical T3 gamma, delta, and epsilon polypeptides are synthesized by TCR gamma lymphocytes and TCR alpha beta lymphocytes. However, the processing of T3 delta oligosaccharides is distinct in the two cell types. This observation may suggest distinct quaternary structures of these receptor complexes. Despite these structural differences, the T3 molecule on TCR gamma lymphocytes is functional. It is associated with and comodulates with TCR gamma and it serves as a substrate for protein kinase C mediated phosphorylation. Anti-T3 monoclonal antibodies induce a rapid increase in cytoplasmic free calcium, indicating that the receptor complex is involved in signal transduction and triggering of TCR gamma lymphocytes. PMID- 3108882 TI - Protein-nucleotide contacts in the immunoglobulin heavy-chain promoter region. AB - Immunoglobulin heavy-chain variable-region genes contain the octanucleotide ATGCAAAT upstream from the site of transcription initiation. The complement of this sequence, in the reverse orientation, is found at an identical location in light-chain variable-region genes. This sequence element is thought to be involved in the lymphoid-specific expression of immunoglobulin genes. Analysis of nuclear extracts from both lymphoid and nonlymphoid cells in a gel migration inhibition assay, using an immunoglobulin promoter region fragment containing the octamer, reveals multiple migration-retarded species that represent specific DNA protein complexes. The number and relative level of these complexes vary with cell type; some complexes are detected with all extracts, whereas one complex is lymphoid-specific and may represent an interaction involved in the lymphoid restricted expression of immunoglobulin genes. Mitogenic stimulation of a B lymphoid line can increase the level of the protein responsible for this lymphoid specific complex. Analysis of the complexes detected in the gel migration inhibition assay by DNase I protection ("footprinting") has revealed that all of these DNA-protein complexes involve contact of the protein with the nucleotides of the octamer. One complex, present in both lymphoid and nonlymphoid cells, displays an additional DNA-protein contact adjacent to the octamer. Our results also indicate that the interaction of proteins with the octameric sequence can cause a local alteration in the structure of the DNA helix. PMID- 3108883 TI - The T-cell receptor gamma chain-CD3 complex: implication in the cytotoxic activity of a CD3+ CD4- CD8- human natural killer clone. AB - A subset of human T cells has recently been described. These cells express the CD3 complex but they do not carry the classical T-cell receptor (TCR)-alpha/-beta heterodimer on their surface (WT31- CD3+). Instead, they express a TCR-gamma chain associated with another type of polypeptide termed TCR-delta. We report here that a T-cell clone with natural killer (NK)-like activity, WM-14, had a disulfide bridged TCR-gamma homodimer associated with CD3 on its surface. The TCR gamma chains of WM-14 cells were present in three different glycosylation forms of 43, 40, and 38 kDa, but they appeared to contain the same polypeptide backbone. Since cytotoxicity by WM-14 could be inhibited by anti-CD3 antibodies, we concluded that the TCR-gamma-CD3 complex was involved in the NK-like unrestricted killer activity. Although normal CD3-gamma, CD3-delta, and CD3 epsilon chains were present in this clone, the association with the TCR-gamma homodimer may be the cause of a complete processing of the N-linked oligosaccharides attached to the CD3-delta chain. PMID- 3108885 TI - Lysine-156 and serine-119 are required for LexA repressor cleavage: a possible mechanism. AB - LexA repressor of Escherichia coli is inactivated in vivo by a specific cleavage reaction requiring activated RecA protein. In vitro, cleavage requires activated RecA at neutral pH and proceeds spontaneously at alkaline pH. These two cleavage reactions have similar specificities, suggesting that RecA acts indirectly to stimulate self-cleavage, rather than directly as a protease. We have studied the chemical mechanism of cleavage by using site-directed mutagenesis to change selected amino acid residues in LexA, chosen on the basis of kinetic data, homology to other cleavable repressors, and potential similarity of the mechanism to that of proteases. Serine-119 and lysine-156 were changed to alanine, a residue with an unreactive side chain, resulting in two mutant proteins that had normal repressor function and apparently normal structure, but were completely deficient in both types of cleavage reaction. Serine-119 was also changed to cysteine, another residue with a nucleophilic side chain, resulting in a protein that was cleaved at a significant rate. These and other observations suggest that hydrolysis of the scissile peptide bond proceeds by a mechanism similar to that of serine proteases, with serine-119 being a nucleophile and lysine-156 being an activator. Possible roles for RecA are discussed. PMID- 3108884 TI - The retinal ganglion cell mosaic defines orientation columns in striate cortex. AB - A computer simulation was used to demonstrate that the tangential organization of orientation columns is a natural consequence of the orderly projection of the mosaic of retinal ganglion cells onto the visual cortex. Parameters of the simulation were taken from published anatomical and electrophysiological data, and the resulting columnar organization of the simulated visual cortex shows many similarities with observations from animals. The model is able to account for a variety of experimental observations, including the presence of orientation columns in visually inexperienced animals. PMID- 3108887 TI - Contribution of a p75 interleukin 2 binding peptide to a high-affinity interleukin 2 receptor complex. AB - There are at least two forms of cellular receptors for interleukin 2 (IL-2); one with a very high affinity and the other with a lower affinity. We identified a non-Tac IL-2 binding peptide with a relative molecular weight of 75,000 (p75). Cell lines bearing either the p55 Tac or the p75 peptide alone manifested low affinity IL-2 binding, whereas a cell line bearing both peptides manifested both high- and low-affinity receptors. After the internalization of labeled IL-2 through high-affinity receptors, the p75 peptide could not be detected by cross linking studies. Furthermore, fusion of cell membranes from low-affinity IL-2 binding cell lines bearing the Tac peptide alone with membranes from a cell line bearing the p75 peptide alone generated hybrid membranes bearing high-affinity receptors. These results suggest a multichain model for the high-affinity IL-2 receptor in which high-affinity receptors would be expressed when both Tac and p75 IL-2 binding peptides are present and associated in a receptor complex. PMID- 3108886 TI - Purified prion proteins and scrapie infectivity copartition into liposomes. AB - Considerable evidence indicates that the scrapie prion protein (PrP 27-30) is required for infectivity. Aggregates of PrP 27-30 form insoluble amyloid rods that resist dissociation by nondenaturing detergents. Mixtures of the detergent cholate and phospholipids were found to solubilize purified PrP 27-30 in the form of detergent-lipid-protein complexes. Removal of the cholate by dialysis resulted in the formation of closed liposomes. Both the detergent-lipid-protein complexes and the liposomes often but not always exhibited a 10-fold increase in scrapie infectivity compared to that observed with the rods. No evidence for a prion associated nucleic acid could be found when the phospholipid vesicles containing PrP 27-30 were digested with nucleases and Zn2+ under conditions that allowed hydrolysis of exogenously added nucleic acids. No filamentous or rod-shaped particles were found amongst prion liposomes by electron microscopy in our search for a putative filamentous "scrapie virus." The partitioning of PrP 27-30 and scrapie infectivity into phospholipid vesicles contends that PrP 27-30 has a central role in scrapie pathogenesis, establishes that the prion amyloid rods are not essential for infectivity, and argues that prions are fundamentally different from viruses. PMID- 3108888 TI - Rearrangement and expression of rabbit immunoglobulin kappa light chain gene in transgenic mice. AB - To determine whether a foreign unrearranged immunoglobulin gene can be functionally rearranged and expressed in vivo, a rabbit b9 kappa light chain gene construct containing a single germ-line kappa chain variable (V) region gene (V kappa), the five kappa chain joining (J) segments (J kappa), and the kappa chain constant (C) region germ-line gene (C kappa) was introduced into fertilized mouse eggs. Eleven transgenic mice carrying 1-30 copies of the rabbit kappa gene construct were obtained. Rearrangement of the transgene due to V kappa-J kappa recombination was observed in the spleen of all the mice lines analyzed. Only the J kappa 1 and J kappa 2 segments, which have canonical sequences for rearrangement and high-level expression, are utilized in assembly of the rabbit gene. V kappa-J kappa 1 and V kappa-J kappa 2 joining was also observed in the thymus but not in nonlymphoid tissue. Polyadenylylated rabbit kappa chain transcripts of 1.2 kilobases were found in the spleen of the transgenic mice. The level of transcription was low despite a high level of rearrangement. Three transgenic mice lines secreted kappa light chains encoded by the foreign rabbit gene. Serum rabbit kappa chains were associated with mouse mu and gamma 1 heavy chains. However, hybrid antibody molecules containing both rabbit and mouse kappa light chains were also found in the serum of these animals. These results suggest that, although the rabbit kappa chain gene construct contains the necessary sequences for gene assembly, sequences implicated in stage- and tissue-specific regulation of kappa chain gene rearrangement are either missing or not recognized by mouse lymphoid cells. PMID- 3108889 TI - Cloning of a cDNA encoding a surface antigen of Schistosoma mansoni schistosomula recognized by sera of vaccinated mice. AB - Spleen cells of mice vaccinated with radiation-attenuated Schistosoma mansoni cercariae were used to produce monoclonal antibodies directed against newly transformed schistosomular surface antigens. One of these monoclonal antibodies recognized a polypeptide of 18 kDa. This glycoprotein was purified by monoclonal antibody immunoaffinity chromatography and a polyclonal antiserum was prepared against it. Immunofluorescence assays showed that the polyclonal antiserum bound to the surface of newly transformed schistosomula and lung-stage organisms but not to the surface of liver-stage and adult worms. Using this polyclonal antiserum we isolated recombinant clones from an adult worm cDNA expression library constructed in lambda gt11. Clone 654.2 contained an insert of 0.52 kilobase and hybridized to a 1.2-kilobase mRNA species from adult worms. Most importantly, clone 654.2 produced a fusion protein of 125 kDa that was reactive with sera of vaccinated mice that are capable of transferring resistance. This result encourages future vaccination trials with the fusion protein. PMID- 3108890 TI - The toxic effects of tumor necrosis factor in vivo and their prevention by cyclooxygenase inhibitors. AB - Tumor necrosis factor (TNF) is a macrophage product under active study as an anticancer drug. However, this agent can be very toxic and has been implicated in the pathogenesis of endotoxic shock. After intravenous injection of human recombinant TNF (4 micrograms/g), growing rats showed an unusual constellation of physiological responses, and all died within 2-4 hr. In 1 hr, TNF caused a sharp fall (2.5 degrees C) in body temperature and a large increase in plasma prostaglandin E2 levels. Blood glucose initially increased, but then a profound hypoglycemia developed by 2 hr. The TNF-treated animals also showed diarrhea, cyanosis, and a severe metabolic acidosis. A single injection of the cyclooxygenase inhibitors indomethacin or ibuprofen before the TNF treatment completely prevented the rapid killing and reduced eventual lethality by 70%. These agents blocked prostaglandin E2 production and prevented the hypothermia, changes in blood glucose, acidosis, and other symptoms. Since similar physiological changes have been reported after endotoxin injection, our data support the suggestion that TNF production is a critical factor in the development of septic shock. These findings also indicate that increased production of prostaglandins or thromboxanes is important in endotoxic shock and argue that cyclooxygenase inhibitors should be useful in its therapy. Indomethacin did not block the cytotoxic effects of TNF in vitro on several transformed cell lines (HeLa, Me 180, or L929). Therefore, combined use of TNF with a cyclooxygenase inhibitor may allow safer administration of high doses of this polypeptide to cancer patients. PMID- 3108892 TI - [The role of the expert in directive functions which appears in legislation from 1925 to date]. PMID- 3108891 TI - Active immunization against renin in normotensive marmoset. AB - Primate renins (human and monkey) are very similar. We used pure human renin to immunize marmosets (Callithrix jacchus) and thereby produce a chronic blockade of the renin-angiotensinogen reaction. After a control period of 2 months, five male marmosets, on their usual sodium-poor diet, were immunized against pure human renin by three subcutaneous injections of 30 micrograms each, with complete and then incomplete Freund's adjuvant. Three marmosets were injected with adjuvant only and served as controls. Blood sampling and blood pressure measurements were performed weekly. After the third injection, the five marmosets immunized against renin developed a high titer of renin antibodies (50% binding of 125I-labeled human renin at a dilution of greater than or equal to 1:10,000). The antibodies inhibited the enzymatic activity of both marmoset and human renins. At the same time, systolic blood pressure decreased significantly from 125 +/- 13 mm Hg to 87 +/- 8 mm Hg (mean +/- SD; 1 mm Hg = 133 Pa). Plasma renin enzyme activity was undetectable in three animals. Plasma aldosterone decreased significantly. After 1-4 months with low blood pressure, a normal urinary output, and a normal plasma creatinine, the five marmosets became sick and died within one month. At autopsy an immunological renal disease, characterized by the presence of immunoglobulin and macrophage infiltration colocalized with renin, was found. Granulomatous formations, probably due to Freund's adjuvant, could be seen in the lungs and in the kidney. No immunoglobulin was detectable in extrarenal vessels or in other organs. These experiments demonstrate that, in this primate, a chronic blockade of the renin-angiotensin system can be achieved by active immunization against homologous renin, but this blockade is associated with the development of an autoimmune disease localized in the kidney. PMID- 3108893 TI - [Vascular access for hemodialysis]. PMID- 3108895 TI - [Training of an intermediate nursing staff: a cultural problem]. PMID- 3108894 TI - [Hemodialysis in non-uremic patients]. PMID- 3108896 TI - [The nursing profession and liberty]. PMID- 3108897 TI - [The incorrect use of gloves]. PMID- 3108898 TI - [A unique national agreement for nursing services in a free professional environment. Let us talk about it]. PMID- 3108899 TI - Food allergies: diagnosis and management. PMID- 3108900 TI - The early phylogenetic origin of antibody gene structure and function. PMID- 3108901 TI - Blood cell changes during encapsulation reactions in Drosophila. PMID- 3108902 TI - Implications of IL-2 in normal and disturbed immune functions in the chicken. PMID- 3108903 TI - [The stability of an emulsion for parenteral nutrition: Trive 1000]. PMID- 3108904 TI - Arachidonic acid metabolism in a cloned strain of rat pituitary tumor cells: correlation between 15 hydroxyeicosatetraenoic acid release and the prolactin secretory process. AB - We investigated the involvement of arachidonic acid metabolites in basal and thyrotropin releasing hormone (TRH) stimulated prolactin release by GH3 cells, a cloned strain of rat pituitary tumor cells. GH3 cells spontaneously released 9 and 15 HETEs and the 15 HETE release was greater than that of 9 HETE. When the cells were challenged by 10(-5) M AA, they were able to produce 5, 9, 12 and 15 HETEs. 10(-6) M TRH only stimulated the release of the two metabolites synthesized by the basal cells (15 and 9 HETEs). This release depended on the length of stimulation by TRH. When both AA and TRH were added, there was an increase in 15 and 9 HETE production. In all cases, more 15 HETE was released than other metabolites. In dose-response studies using TRH concentrations of 10( 6) M to 10(-12) M, the highest level of 9 HETE release was obtained at 10(-11) M TRH and the highest release of 15 HETE was at 10(-9) M TRH. PRL secretion by GH3 cells challenged by TRH showed the same pattern as 15 HETE release, and the correlation between PRL and 15 HETE was significant (p less than 0.001). These data indicate that 15 HETE is the lipoxygenase metabolite released in the largest amounts by GH3 cells and suggest some physiological interaction between 15 HETE and TRH in the control of PRL secretion. PMID- 3108905 TI - Cyclooxygenase and lipoxygenase metabolites during platelet aggregation: quantitative measurement by negative ion chemical ionization--gas chromatography/mass spectrometry. AB - This study was aimed at investigating systematically the aggregation of human gel filtered platelets induced by various physiological stimuli such as thrombin (0.25 U/ml), collagen (2 micrograms/ml), a mixture of thrombin and collagen, and ADP (2-5 microM). For quantitative measurement of TXB2, PGF2 alpha and 12-HETE, negative ion chemical ionization-gas chromatography/mass spectrometry using stable isotope dilution was applied. Stimulation by thrombin, collagen and the combined agonists resulted in an increase of TXB2 (up to 54 ng/1 X 10(8) platelets) and 12-HETE (up to 44 ng/1 X 10(8) platelets) during platelet aggregation. The stimulation with ADP showed only little increase of these metabolites and this only during the second wave of aggregation. Very little amounts of PGF2 alpha were produced during thrombin stimulated aggregation. PMID- 3108906 TI - Microsomal arachidonate bioconversion in rat small intestine during maturation. AB - This study was designed to compare prostaglandin (PG)-synthesizing activity in rat small intestinal microsomes in the 1st, 3rd, and 6th weeks of life and at maturity (greater than 100 days). When an incubation system was used containing 2 mg microsomal protein, 0.5 mM (-)-epinephrine and 1 mM reduced glutathione, the highest PG-synthesizing activity was achieved by incubating 0.157 mM 1-(14)C arachidonate (specific activity 2.6 X 10(6) dpm/mumol) at 37 degrees C for 5 min. The labeled metabolites were extracted and then separated with high performance liquid chromatography. The four PGs analyzed were 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2, prostaglandin F2 alpha and prostaglandin E2. Enzymatic activity for the synthesis of 6-keto-PGF1 alpha was much higher than that for the other PGs. A significant difference was observed for the bioconversion from arachidonate to 6-keto-PGF1 alpha and total PGs among the four age groups of rats. The postweanling groups (week 6 and adult) showed significantly higher enzymatic activities for the syntheses of 6-keto-PGF1 alpha and total PGs than did the preweanling groups (weeks 1 and 3). PMID- 3108907 TI - Electrophysiologic and antiarrhythmic actions of sulphinpyrazone and its sulfide metabolite G25671. AB - In anesthetized dogs, the cumulative intravenous administration of 1.0-40.0 mg/kg sulphinpyrazone failed to alter the ventricular excitation threshold, ventricular refractory period and ventricular fibrillation threshold determined during nonobstructed coronary blood flow. Sulphinpyrazone, however, did attenuate the reduction in the ventricular fibrillation threshold occurring during transient myocardial ischemia. G25671, the sulfide metabolite of sulphinpyrazone, failed to alter ventricular refractoriness and 'nonischemic' ventricular fibrillation thresholds, and was minimally effective in reducing the decrease in 'ischemic' fibrillation thresholds when administered in cumulative intravenous doses of 5.0 20.0 mg/kg. In conscious dogs in the subacute phase of anterior myocardial infarction, the administration of a cumulative 10.0-40.0 mg/kg sulphinpyrazone failed to alter the mode of induction, rate or morphology of ventricular tachyarrhythmias initiated by programmed ventricular stimulation. These data suggest that neither sulphinpyrazone nor its sulfide metabolite possess primary electrophysiologic properties which might contribute directly to significant antiarrhythmic or antifibrillatory activity. PMID- 3108908 TI - 7-ethoxycoumarin O-deethylation in perfused livers from ethanol-fed rats: evidence for an important role of mitochondrial reducing equivalents. AB - Rates of 7-ethoxycoumarin (7EC) O-deethylation in perfused livers were increased approximately 3-fold by chronic ethanol feeding. The acute addition of ethanol (5 mM) and antimycin A (0.03 mM) strongly inhibited 7EC metabolism in perfused livers from ethanol-fed rats, but less inhibition was observed when these agents were added to microsomes or to perfused livers from control rats. The activity of the hepatic pentose phosphate cycle in perfused livers was assessed by comparing 14CO2 release during the infusion of 1-14C-glucose or 6-14C-glucose. 7EC infusion caused a 3-fold greater increase in 14CO2 production from 1-14C-glucose in a liver from a control rat than in a liver from an ethanol-fed rat, indicating greater hepatic pentose cycle activity in livers of control rats. Thus, the pronounced inhibition of 7EC metabolism caused by infusion of ethanol and antimycin A may be explained by a greater dependency on mitochondrial sources of NADPH in livers of ethanol-fed rats. Dinitrophenol (0.05 mM) did not inhibit 7EC metabolism in perfused livers, indicating that a reduction in the cellular redox state, and not diminished energetics, is involved in the mechanism of inhibition produced by antimycin A. PMID- 3108909 TI - Serotonin reuptake inhibition vs. norepinephrine reuptake inhibition: a double blind differential-therapeutic study with fluvoxamine and oxaprotiline in endogenous and neurotic depressives. AB - The antidepressive properties of the specific serotonin reuptake inhibitor fluvoxamine and the specific norepinephrine reuptake inhibitor oxaprotiline were investigated in a sequential design with the aim of evaluating the hypothesis that two distinct biochemical subtypes of depression exist. Responders were treated for 7 weeks with the compound to which they had responded. After 1 placebo week, the nonresponders were switched to the alternative compound. An evaluation of the data obtained during the 3-week treatment periods from 24 patients (37 trials) with major depression revealed a highly significant reduction of Hamilton Scores with both compounds, oxaprotiline and fluvoxamine. If the patients with major depression are subdivided into two groups, endogenous depressives and neurotic depressives, there is no significant difference between the therapeutic improvements (both compounds) achieved in the two groups. The data shows that only about 20% of the nonresponders on one compound responded to the alternative drug, whereas 90% of responders (within 3 weeks) were still responders after 7 weeks. The data are at variance with the concept of two distinct biochemical subtypes of depression (serotonergic vs. norepinephrinergic). Dexamethasone suppression tests, performed in 23 patients, gave no prognostic hint as to whether the patients reacted well to drug therapy or not. PMID- 3108910 TI - Involvement of a dopaminergic mechanism in the response of growth hormone to thyrotropin releasing hormone in patients with major depression. AB - In an attempt to establish whether, in patients with major depression, dopaminergic receptors are involved in the release of growth hormone (GH) induced by thyrotropin releasing hormone (TRH), eleven subjects were tested with TRH (200 micrograms in an i.v. bolus) with or without concomitant treatment with domperidone (10 mg in an i.v. bolus 10 min before TRH), an antidopaminergic agent which does not readily cross the blood-brain barrier. In 7 out of the 11 patients, TRH strikingly increased GH levels (responders) (the mean peak level was 9 times higher than basal value), whereas it was without effect in the remaining 4 patients (non-responders). When the responders were treated with domperidone before TRH injection, TRH-induced GH increase was still present, but it was significantly lower (the mean peak level was 5.3 times higher than basal value) than in the TRH test (p less than 0.02). These data suggest that the paradoxical response of GH or TRH in patients with major depression involves a dopaminergic mechanism active at sites situated outside the blood-brain barrier. PMID- 3108911 TI - Effect of the Medicare prospective payment system on the utilization of physical therapy. AB - The purpose of this study was to examine the effect of the Medicare prospective payment system on the utilization of physical therapy for patients served by Medicare. The total number of inpatient and outpatient physical therapy referrals and the percentage of physical therapy Medicare referrals from January 1981 through May 1985 for the 336 acute care beds in the county selected for this study were analyzed. The results indicated that acute care inpatient and outpatient physical therapy Medicare referrals have increased significantly since the implementation of the diagnostic related group system. The results indicate that physical therapy is being used increasingly to rehabilitate patients within the time and economic constraints established by the Medicare prospective payment system. PMID- 3108912 TI - The influence of Ca2+ on the turbidity of DPPC-DMPA vesicles within the temperature range of the phase transition. AB - The influence of the addition of Ca2+ on the phase behaviour of vesicles, composed of dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidic acid (DMPA) in a ratio of 4 to 1, has been investigated by means of turbidity measurements. As expected one single phase transition for the mixed phospholipids was observed in the absence of Ca2+. Passing through the temperature range of this transition after the addition of Ca2+, conditions appeared to favor fusion of the vesicles. A possible reason for this is that during the transition Ca2+ may permeate through the vesicle membranes and gain access to the inside DMPA binding sites. Therefore it is not unambiguously possible to determine phase transition temperatures from the turbidity changes that occur under these conditions. However, when within the temperature range of the phase transition of the mixed phospholipids the influence of Ca2+ addition to the vesicles was recorded isothermally, at each temperature separately, the final plot of turbidity versus temperature turned out to be far less confused by fusion events and adopted the form of two separate phase transitions. The temperatures at which these two transitions occur closely resemble the phase transition temperatures that may be observed in the absence of Ca2+ for DMPA and DPPC alone, 39 degrees C and 43 degrees C respectively. The results of this study suggest that when Ca2+ has only access to the outside of the vesicle membranes it may segregate the neutral and the acidic phospholipids into separate domains, both domains adopting their proper phase condition at the actual temperature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108914 TI - [Modification of psychophysical performance of the human by anticonvulsants]. AB - Antiepileptics can impair the performance of subjects in both acute and subacute doses. The effects of phenobarbital and its derivatives and benzodiazepines are stronger in this respect than that of phenytoin, ethosuccimides and valproic acid. Carbamazepine, in contrast, has rather a stimulatory action. Impaired cognition, psychomotor performance and emotions must also be expected under therapeutic conditions. Attention is drawn to various factors that may influence the results of tests, including the dose and blood concentration, interval between application and test, initial performance of the probands or patients, levels of vigilance and personality structure. Lack of compliance is particularly important since adaptation and readaptation processes that can be dangerous take place in these patients. The careful exploration of side-effects on the patient may have a decisive influence on practicability and cost if the relationship between patient and doctor is good. PMID- 3108913 TI - [Pneumonitis as a consequence of gold therapy]. PMID- 3108915 TI - [Evaluation of psychological performance parameters in the use of Finlepsin and Convulsofin]. AB - The psychomotorial tempo was investigated in a particular case study of seven patients during the introduction of Convulsofin respectively Finlepsin. For this end the reaction rate was registered at the same moment as the EEG. The valuation of the psychological parameters referred to optimal courses of the introduction. Three months after the beginning of introduction the examined criterions (psychological, clinical, pharmacological, EEG) showed a equally positive tendency. An observation period for the prognosis valuation of at least three months is recommended. Negative deviations can be involved by drugs or by disturbances of the compliance. PMID- 3108916 TI - [Automatic detection of transient potentials in the EEG]. AB - A classifier based on the linear regression model was developed to automatically detect sharp transients in EEG, matching the definition of spikes and sharp waves accepted by IFSECN. Practical applications proved the accuracy of the method which succeeded in detecting 84% of sharp transients previously found by an experienced electronencephalographer. Computerized search for sharp transients in EEG records will be particularly useful in long term EEG records obtained from epileptic patients. PMID- 3108917 TI - Planning psychiatric treatment and rehabilitation for the long-term patient. PMID- 3108918 TI - Mechanism of action of ECT in major depressive disorders: a neuroendocrine interpretation. AB - Electroconvulsive therapy (ECT) is often efficacious in severe depression, and it is occasionally used in the treatment of schizophrenia. The mechanism of action of ECT is still poorly understood. We evaluated thyroid-stimulating hormone (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH) after a first ECT and at the end of a series of seven ECTs in eight unipolar depressed patients with blunted basal TSH/TRH response, eight unipolar depressed patients with normal TSH/TRH response, and eight schizophrenic patients. The hormone patterns obtained after the first ECT showed an increase in prolactin and a decrease in TSH in all groups of patients, suggesting a nonspecific response. At the end of the therapeutic course, TSH responses increased in both groups of depressed patients, and the elevation was more relevant in depressed patients with normal TSH/TRH. Our data suggest that the mechanism of action of ECT becomes more specific when it is performed chronically and differs according to the organic substrate underlying different mental disorders. Moreover, an aminergic activation in the two groups of depressed patients seems to take place. PMID- 3108919 TI - Serum thyrotropin (TSH) responses to thyrotropin-releasing hormone (TRH) in patients with anorexia nervosa and bulimia: influence of changes in body weight and eating disorders. AB - Serum thyrotropin (TSH) responses to thyrotropin-releasing hormone (TRH) were studied in 47 women with anorexia nervosa (AN) (group I) and in 11 bulimic patients of normal weight (group II). In group I, TSH responses were low in nine patients, delayed in 32 and normal in six. Patients with a normal TSH response had a lesser degree of anorexia than those with a delayed TSH response. Bulimia and vomiting were more frequently observed in the low response group. The maximum increase in TSH concentrations following TRH administration in the group I patients with vomiting (4.0 +/- 0.90 microU/ml, mean +/- S.E.) was significantly lower than that in the group I patients without vomiting or in normal controls (11.2 +/- 0.82 microU/ml and 11.1 +/- 2.34 microU/ml, respectively). Twenty-five patients with abnormal TSH responses in group I were retested after weight gain. Initially, TSH responses were low in six and delayed in 19. Following weight recovery, responses continued to be abnormal in five of the six and in eight of the 19, respectively. The symptoms of eating disorders continued in all patients with abnormal TSH responses even after weight recovery, whereas patients with normal responses after weight gain recovered from all symptoms. Of 11 patients in group II, six had abnormal TSH responses to TRH; the responses were delayed in four and low in two. Patients with normal responses had a lesser degree of eating disorder, compared with abnormal responders. These observations suggest that abnormal TSH responses in patients with AN were not necessarily due to weight loss alone; rather, they may be related to the eating disorder itself. PMID- 3108920 TI - Effects of ECT on the TRH stimulation test. AB - The prognostic value of the TRH stimulation test was evaluated in 23 inpatients with major depressive disorder before and after a trial of ECT. In contrast to previous reports, the peak TSH response to TRH was significantly decreased after treatment compared with before treatment. This effect was consistent across individuals and subgroups (responders/nonresponders; unilateral/bilateral ECT). The particular ECT technique used in the study may account for the discrepancies between these findings and those previously reported by other authors. PMID- 3108921 TI - Dose level effects of triazolam on sleep and response to a smoke detector alarm. AB - Thirty-six young adult, male subjects with sleep-onset insomnia were equally divided into placebo, 0.25 mg, and 0.5 mg triazolam groups to examine the effects of the hypnotic, with particular attention to dose level on efficacy, sleep stages, and awakening to a smoke detector alarm. On nights 1 and 4 of a five consecutive-night protocol, a standard home smoke detector alarm was sounded during stage 2, 5 min after sleep onset, in slow wave sleep (SWS), and at the time of the early morning awakening. The alarm registered 78 dB SPL at the pillow. EEG arousal latency and reaction time to a button press were studied. Failure to awaken to three 1-min alarm presentations was scored as "no response." Both dose levels produced similar reductions in sleep latency, decreases in SWS, increases in stage 2, and increases in sleep efficiency. Both dose levels showed similar sedative effects to the smoke alarm. Fifty percent of triazolam subjects failed to awaken on night 1 during SWS, and EEG arousal and response latencies were significantly slowed. Some drug tolerance or sensitization to the alarm was seen by night 4. By morning, all subjects were easily awakened on both nights. The 0.25 mg dose is clearly an effective dose level for both sleep efficacy and sedative effects to outside noise, which in some instances could pose potential problems. PMID- 3108922 TI - Pharmacokinetics of haloperidol in psychotic patients. AB - Nine psychotic patients under continuous oral treatment with haloperidol were randomly given a test dose of 1.5-5 mg haloperidol orally and/or intravenously. Serum levels of haloperidol were determined by high performance liquid chromatography and serum concentration data obtained were submitted to pharmacokinetic analysis. The steady state concentration ratio between blood and plasma was determined and found to be 0.79 +/- 0.03. The blood clearance was then calculated to be 550 +/- 133 ml/min. The mean hepatic extraction ratio was intermediate (0.37). Consequently, for a drug mainly eliminated by hepatic metabolism like haloperidol, the total blood clearance and the extent of oral bioavailability can be affected by changes in hepatic blood flow, hepatic enzyme activities and drug binding. During continuous oral treatment with haloperidol, however, it can be shown that changes in the total metabolic capacity of the liver due to hepatic enzyme induction or inhibition should be important for the therapeutic effects of haloperidol. The volume of distribution at steady state (Vdss) was large (7.9 +/- 2.5 l/kg). The terminal half-life was 18.8 h after intravenous and 18.1 h after oral administration. The oral bioavailability (0.60 +/- 0.18) were in accordance with previous results in healthy subjects. A mean lag time after oral dose was 1.3 +/- 1.1 h and a longer absorption half-life (1.9 +/- 1.4 h) was found in the patients compared with healthy volunteers. PMID- 3108923 TI - Sleep improvement in dogs after oral administration of mioflazine, a nucleoside transport inhibitor. AB - Mioflazine, a nucleoside transport inhibitor, was given PO to dogs at doses of 0.04-10 mg/kg. Sixteen hour polygraphic sleep recordings were made and analysis and sleep stage classification was done by computer. Mioflazine decreased wakefulness and increased slow wave sleep, but did not affect the latencies of either REM sleep or slow wave sleep. This increased sleep was due to an increase in the number of light and deep slow wave sleep epochs. The effect lasted for about 8 h. The decreased wakefulness and increased slow wave sleep could be antagonized by the adenosine antagonist caffeine (2.5 and 10 mg/kg, PO); however, there was not a pure antagonistic effect. It might be that the enhancement of slow wave sleep is due to an activation of brain adenosine receptors. This is the first report of a drug acting on adenosine that given orally improves sleep. Mioflazine might be the prototype of substances worth considering for the treatment of a variety of sleep disorders. PMID- 3108924 TI - Differential effects of proglumide on mesolimbic and nigrostriatal dopamine function. AB - Cholecystokinin octapeptide (CCK-8) is prevalent as a co-transmitter in the mesolimbic dopamine pathway. The effect of proglumide, a CCK-8 antagonist, on two acute and one chronic behavioral models of dopamine function was tested. First, haloperidol was used to inhibit stereotypies induced by apomorphine in rats. Pre administration of proglumide significantly shifted the haloperidol dose response curve to the left. Second, rats were injected in the left caudate nucleus with kainic acid. Three weeks later, haloperidol was used to inhibit apomorphine induced circling. Pre-administration of proglumide had no effect on this haloperidol dose response curve. Third, either proglumide, haloperidol, or combined treatment was administered to rats for 2 weeks. In proglumide-treated animals, a significant increase in 3H-spiperone binding sites in the nucleus accumbens was observed. PMID- 3108925 TI - A test of possible cognitive and environmental influences on the mood lowering effect of tryptophan depletion in normal males. AB - In a previous study we found that a tryptophan-deficient amino acid mixture, designed to lower tissue tryptophan and thus brain 5-hydroxytryptamine (5HT) levels, caused a rapid (5 h) lowering of mood in normal males. Because of the importance of this evidence indicating a direct causal connection between low 5HT and low mood, we have now investigated other possible explanations for the mood lowering effect. Research strongly supports the involvement of environmental setting and cognition in the production and experience of emotions. Therefore we investigated how these factors might influence the mood-lowering effects of tryptophan depletion. In an instructional manipulation subjects were either supplied or not supplied with information designed to account for any possible peripheral sensations that might be related to depressive affect. In an environmental manipulation subjects were exposed either to a supportive and comfortable atmosphere (positive environment), or an unrewarding and unstimulating environment (negative environment). In the control group, which received a balanced amino acid mixture, the positive and negative environments had the expected effects on the scores of the Multiple Affect Adjective Checklist, thus indicating the effectiveness of these procedures. In the tryptophan depletion group neither the instructional nor the environmental manipulation had any influence on the mood lowering effect. It may be that tryptophan depletion lowers mood in normal males because low 5HT influences mood directly rather than via cognitive processes. Our data strongly support the idea that 5HT exerts an effect on mood and that low 5HT may, in some patients, be an important factor contributing to the etiology of clinical depression. PMID- 3108926 TI - Amphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: new evidence for central dopaminergic-noradrenergic interactions. AB - A series of experiments examined the effects of lesions of the dorsal noradrenergic bundle (DNAB), induced by 6-hydroxydopamine (6-OHDA), on the behavioural response to systemic and intra-accumbens amphetamine, using a rat analogue of Leonard's 5-choice serial reaction time task for humans. Although the 6-OHDA DNAB lesion produced a profound depletion of cortical noradrenaline (NA) (to around 5% of control levels) it did not impair any aspect of performance on this task. Both systemic and intra-accumbens amphetamine increased behavioural measures of impulsivity of responding, but neither impaired discriminative accuracy in the sham-operated control rats. However, the DNAB lesioned rats did show a discriminative impairment following both low doses of systemic amphetamine, and intra-accumbens amphetamine. The latter effect was antagonised by systemic administration of the specific dopaminergic (DA) antagonist alpha flupenthixol. The DNAB lesion did not alter the effect of amphetamine on any other behavioural measure, including speed and impulsivity of responding. These results suggest that although DA and NA participate in qualitatively different behavioural processes, the effects of DNAB lesions on attentional processes depend on the level of DA activity within the nucleus accumbens. PMID- 3108927 TI - Effect of raphe lesions on the development of chronic tolerance to pentobarbital and cross-tolerance to ethanol. AB - Sham and electrolytic lesions of the dorsal, median, and median + dorsal raphe nuclei were made in different groups of rats, and the differential patterns of regional 5-HT depletion were verified chemically. One week later, an initial dose response curve for the motor impairment effect (moving belt test) of pentobarbital was obtained. Matched subgroups of the animals in each lesioned group received daily gavage with either pentobarbital (50 mg/kg) or water for 36 days. Tolerance to the motor impairment effect of pentobarbital was measured at 4 day intervals. Lesions of the dorsal raphe nucleus had no influence on the development of tolerance, whereas median and median + dorsal raphe lesions resulted in slower development of tolerance, though plasma pentobarbital levels were unaltered. The effect of the combined lesion was similar to that of the median raphe lesion alone. A separate study revealed a similar differential effect of median versus dorsal raphe lesions on the development of cross tolerance to ethanol. PMID- 3108928 TI - The development of thermoregulation after prenatal exposure to alcohol in rats. AB - The effect of prenatal exposure to alcohol on the development of thermoregulation and behavioral thermogenesis was assessed in rats. Pups at 5, 10, 15, and 20 days of age were chosen from litters with one of three prenatal treatment histories: liquid diet with 35% ethanol-derived-calories (35% EDC), pair-fed control (0% EDC), or lab chow control (LC). Subjects were removed from the home nest and had their initial rectal temperatures recorded before placement alone in the center of an observational chamber in a testing room maintained at 23-24 degrees C. Rectal temperatures were recorded again every hour for the next 4 h. Speed to reach the wall for behavioral thermogenesis (wall-huddling) was also measured at each hourly interval. With increasing age, all pups displayed increasing ability to maintain their initial core temperature, but prenatal exposure to alcohol had a significant effect in retarding the development of thermoregulation. At 5 and 10 days of age, alcohol-exposed pups had significantly lower rectal temperatures at 1-4 h out of the nest compared to control pups. In addition, the speed to reach the wall was slower in 35% EDC pups than in pups from the two control groups, suggesting a deficit in behavioral thermogenesis as well. These results agree with others demonstrating alcohol-induced development delays, and may have implications for other behavioral deficits seen after prenatal exposure to alcohol. PMID- 3108929 TI - The benzodiazepine antagonist CGS 8216 decreases both shocked and unshocked drinking in rats. AB - Previous studies of the benzodiazepine antagonist CGS 8216 have reported that this compound may enhance the punishment-induced suppression of behaviour. In order to investigate this phenomenon further, water-deprived rats were trained to drink from a water spout during a multiple schedule with shocked and unshocked components. During the shocked components a very mild electric footshock was presented after every 20th lick. The shock slightly reduced the rate of licking during these components below that which occurred during periods without shock, although this effect decreased during the experiment. CGS 8216 (0.3-10 mg/kg) produced a dose-related reduction in licking during both schedule components. The overall volumes of water consumed were reduced by CGS 8216 as was the number of licks during the first, unshocked schedule component, before shock was applied, showing that the effect on unshocked licking was not due to a generalisation of suppression between periods with or without shock. In contrast to CGS 8216, a dose of 10 mg/kg pentylenetetrazol selectively reduced shocked licking. In a second group of rats which drank under identical conditions but without shock, CGS 8216 again reduced water intake. These results show that CGS 8216 can reduce water intake in rats regardless of whether drinking results in shock presentation. PMID- 3108931 TI - Effects of arecoline and pilocarpine on learning ability in marmosets pretreated with hemicholinium-3. AB - Common marmosets (Callithrix jacchus) were trained to perform serial reversal position discrimination tasks in a Wisconsin General Test Apparatus. Intraventricular injection of hemicholinium-3 4 h before testing resulted in a profound impairment of position discrimination learning which could be overcome by the intramuscular administration of low doses of the muscarinic agonists, arecoline or pilocarpine. PMID- 3108932 TI - Oral tyramine pressor test and the safety of MAO inhibitor drugs. PMID- 3108930 TI - Cognitive effects of L-deprenyl in Alzheimer's disease. AB - Monoamine neurotransmitter systems, along with cholinergic systems, are known to play important roles in cognition, and are disrupted in at least some patients with dementia of the Alzheimer type (DAT). This suggests that monoamine-enhancing drugs might ameliorate cognitive symptoms in certain patients with DAT. L Deprenyl is a monoamine oxidase (MAO) inhibitor which may selectively inhibit MAO B at low doses, while at high doses it nonselectively inhibits MAO-A as well as MAO-B. We studied its effects on several types of cognitive function in 17 patients with DAT. Two doses of L-deprenyl (10 mg/day and 40 mg/day) and placebo were compared in a double-blind, serial treatment design. Episodic learning and memory, knowledge memory, attention, recognition, and performance on a continuous performance task were assessed at baseline and under these drug and placebo conditions. Statistically significant improvement was noted in performance on an episodic memory and learning task requiring complex information processing and sustained conscious effort during treatment with L-deprenyl 10 mg/day. Knowledge memory, intrusions, and other cognitive functions relevant to DAT were not altered by L-deprenyl at either dose. PMID- 3108933 TI - Some limitations of indices derived from signal detection theory: evaluation of an alternative index for measuring bias in memory tasks. PMID- 3108934 TI - Placing long-stay patients in private nursing homes. PMID- 3108935 TI - A survey of the prevalence of schistosomiasis in school children in the Bo and Tongo Field areas of Sierra Leone. PMID- 3108936 TI - Adult immunization should be routine, too. PMID- 3108937 TI - Injury prevention for Indians: was the assessment too early? PMID- 3108938 TI - Knowledge and attitudes of AIDS health care providers before and after education programs. AB - Analysis of the responses of 1,247 health care providers to questionnaires immediately before and after educational programs on acquired immunodeficiency syndrome (AIDS) revealed significant (P less than .05) improvements in accuracy of knowledge about 7 of 15 modes of transmission and 7 of 11 means of infection control. Sizeable percentages, however, continued to believe after the programs that AIDS could be transmitted by casual contact, such as sharing coffee cups. Provider attitudes about caring for persons with AIDS shifted in the direction desired (P less than .001) on six of nine questions. After programs, 92 percent believed that they had sufficient knowledge to protect themselves from getting AIDS, and 79 percent felt professionally competent to care for a person with AIDS. Both before and after programs, providers who established regulations for the care of persons with AIDS and outpatient care providers had the most accurate knowledge and felt most comfortable with persons with AIDS, while inpatient care providers had the least accurate knowledge and felt least comfortable. A 1-month followup of 159 providers revealed that postprogram changes in knowledge and attitudes were largely retained. Results point to the need for education at all levels of the health care system, to a persistent gap in knowledge and attitudes between those persons who establish regulations and those who carry them out, and to the possibility of creating significant changes through education. PMID- 3108940 TI - Importance of WHO and the World Health Assembly to U.S. Public Health and Medicine: a Food and Drug Administration perspective. PMID- 3108939 TI - The association of smoking with clinical indicators of altered sex steroids--a study of 50,145 women. AB - This study was designed to test the association of smoking with four clinically apparent conditions that may be related to altered sex steroids: natural and induced menopause, infertility, oligomenorrhea, and hirsutism. Data were obtained from the personal inventories of 50,145 women ages 20-59 years in TOPS, a weight reduction program. The age-adjusted odds ratios of each condition for heavy smokers compared with nonsmokers were 1.59 for natural menopause, 1.49 for induced menopause, 1.35 for infertility, 1.30 for oligomenorrhea among women younger than 40 years, 1.63 for oligomenorrhea among women 40-49 years, and 1.54 for hirsutism (P less than .05 for oligomenorrhea and P less than .001 for all other risks). The odds ratios were not substantially changed after adjustment for obesity, parity, and husband's education level. These results suggest that smoking may affect the ovaries or hormone metabolism, or both, with medical and cosmetic consequences. PMID- 3108941 TI - A television format for national health promotion: Finland's "Keys to Health". AB - A series of televised risk reduction and health promotion programs have been broadcast in Finland since 1978. The five series of programs were the product of a cooperative effort by Finland's television channel 2 and the North Karelia Project. The series has featured a group of volunteers who are at high risk of diseases because of their unhealthful habits and two health educators who counsel the studio group and the viewers to make changes in health behaviors. The "Keys to Health 84-85" was the fifth of the series and consisted of 15 parts, 35 minutes viewing time each. Results of the evaluation surveys, which are presented briefly, indicate that viewing rates were high. Of the countrywide sample, 27 percent of men and 35 percent of women reported that they had viewed at least three parts of the series. Reported changes in behaviors were substantial among the viewers who had seen several parts of the series and were meaningful, overall, for the entire population. Of the countrywide sample, 7.1 percent of smoking viewers reported an attempt to stop smoking--this number was 3.6 percent of all smokers. The percentages of weight loss among viewers and the total population sample were 3.9 for men and 2.1 for women. The reported reductions in fat consumption were 27.2 percent for men and 15.0 percent for women. The reported effects in the demonstration area of North Karelia were even higher, mainly because of higher viewing rates. PMID- 3108942 TI - Survey of public knowledge about digestive health and diseases: implications for health education. AB - Increasing emphasis in recent years has been placed on health promotion, prevention, and the self-management of health care. These strategies presume the public has sufficient levels of relevant health information, as well as necessary attitudes and skills for the effective use of this information in the management of their own health care. This study tests this assumption as it relates to the level of public knowledge of digestive health and disease, a major health concern affecting an estimated 1 in 10 Americans. This paper reports results of a telephone survey of a representative national sample administered to 1,250 Americans in May 1983 that was designed to assess their level of information about digestive health and disease, comfort in communicating about digestive problems, and preference for health information sources. The results indicate that the American public is largely uninformed and misinformed about digestive health and disease, and they underscore the need for disseminating relevant health information about digestive health and disease to the public to facilitate prevention of digestive health problems and self-management of digestive health care. Health information dissemination is severely complicated by the widespread stigma associated with digestive topics, manifested in the American public's general discomfort in communicating with others about digestive health. These factors necessitate development of sensitive and pervasive digestive health promotion and education programs in the United States. PMID- 3108943 TI - Ethnic differences in growth and nutritional status: a study of poor schoolchildren in southern New Jersey. AB - The growth and nutritional status of 2,056 schoolchildren from a poor community in southern New Jersey were assessed. Age-adjusted differences in growth among black, white, and Hispanic children were examined. Black youths were 2.5 centimeters (cm) taller (P less than .001) and 0.9 kilograms (kg) heavier than white youths (P less than .05). Black girls were 4.1 cm taller (P less than .001) and 2.8 kg heavier than white girls (P less than .01). Hispanic girls were 1 kg heavier (P less than .05) and 0.9 cm taller (not significant) than white girls. There was little difference in growth between Hispanic and white youths. Children were assessed with the use of the Centers for Disease Control's nutritional surveillance cutpoints; less than 5 percent of each ethnic group fell below the fifth percentile, according to the National Center for Health Statistics' weight for-height standards. White and Hispanic youths were twice as likely as blacks to fall below the 5th percentile for stature or to be overweight (above the 95th percentile for weight-for-height). Compared with black girls, white and Hispanic girls were three to four times more likely to fall below the fifth percentile for stature. The prevalence of short stature was also higher among white girls (15.9 percent) compared with Hispanics (10.3 percent). There was little difference in the prevalence of overweight by ethnic group for girls. These data show that white children from poor communities have decreased growth and suggest that they may be at increased risk of nutritional problems. PMID- 3108944 TI - The Preventive Health and Health Services Block Grant: the Massachusetts experience. AB - The Preventive Health and Health Services Block Grant funds a variety of disparate programs in health promotion and disease prevention. Many of these programs were funded by categorical grants to the States prior to the creation of this block grant in 1981. This block grant allows States to set priorities among the different programs by shifting their funding allocations. In addition, there is considerable opportunity to use these funds creatively in shaping the content of their programs. The Massachusetts Department of Public Health's experience with this block grant is reviewed, showing the grant's critical importance in the department's statewide disease prevention efforts. In order to maximize public health impact, the department has shifted its funding allocations based on explicit criteria. These criteria represent a model that may have widespread applicability for other State health departments. PMID- 3108945 TI - The Massachusetts program for reducing the risk of formaldehyde exposure. AB - Urea formaldehyde foam insulation in homes has caused increasing concerns about the adverse health effects associated with residential exposure to formaldehyde emissions. These health effects cover a broad spectrum of symptoms, including neurophysiological effects, respiratory irritations, and eye and skin irritations. Recent studies have also suggested a possible correlation between exposure to formaldehyde vapors and cancer. In 1979, following hundreds of complaints of adverse health effects from occupants of dwellings insulated with urea formaldehyde foam insulation (UFFI), the Massachusetts Department of Public Health issued regulations banning the new installation of UFFI in Massachusetts. New State legislation was adopted in 1986 which reformulated UFFI policy. The law established a minimum concentration of formaldehyde of 0.1 parts per million (ppm) below which removal of the insulation is not required or encouraged. A trust fund financed by industry was established to pay for air testing and for the removal of UFFI from homes if the formaldehyde level exceeds the statutory minimum of 0.1 ppm or if an occupant experiences adverse health effects attributable to the insulation. Based on the Massachusetts experience, these requirements have been identified: the need for flexibility and midcourse corrections in the development of health policy to allow for the incorporation of new scientific information or changes in the economic or political environment, the need for close coordination with all affected parties, and the need for scientific and technical policy development to be joined with economic and political perspectives to ensure smooth implementation of health policies. PMID- 3108946 TI - Recency of Pap smear screening: a multivariate model. AB - Most descriptive reports of women who have not received recent Pap smear screening have been limited to bivariate descriptions. The purpose of this study was to develop a multivariate model to predict the recency of Pap smear screening. A systematic sample of women residents, aged 25 to 74 years, in upstate New York was selected. The women were asked to report use of Pap smear screening during several time periods, their congruence with recommended medical practice, general use of medical services, and a variety of sociodemographic indicators. A log linear weighted least squares regression model was developed, and it explained 30 percent of the variance in recency of Pap smear screening behavior. While the sociodemographic variables were important predictors in the model, the medical care variables were the strongest predictors of recent Pap smear use. A significant relationship between race and recency of Pap smear testing was not supported by these data. PMID- 3108947 TI - A survey of pediatricians' attitudes and practices about maternal employment. AB - A survey of 281 members (31 percent) of the Texas Pediatric Society was performed in 1981 to assess members' knowledge of, attitudes toward, and practices regarding mothers who work outside the home. Only 15 percent correctly answered two of three knowledge questions about maternal employment. Thirty-five percent of the pediatricians failed to inquire about maternal employment. Although only 1 percent advised all mothers not to work, 22 percent said that mothers with children at home should not work. Most pediatricians had traditional conservative attitudes and opinions (exemplified by the statement "a woman's place is in the home") in regard to two factors, "acceptability of maternal employment" and "effects of maternal employment on children." More liberal views were associated with more recent graduation from medical school, being a woman, having a working wife, being in favor of wife's working status, and knowledge of statistics concerning maternal employment. These results suggest that if the practices of those Texas pediatricians who responded correspond with other pediatricians' practices in the United States, a large proportion of pediatricians may not be providing adequate support for the 17 million working mothers and their children. PMID- 3108948 TI - Users of reproductive health clinic services in a school pregnancy prevention program. AB - Although the potential of school-based programs in the prevention of adolescent pregnancy is well recognized, few have been evaluated. This paper describes the use of a reproductive health care clinic associated with a school pregnancy prevention program which had demonstrated success. The program operated in one junior and one senior high school in a large city during the 3 school years from 1981 to 1984. Three facets of the 818 users of the program clinic are explored: who enrolled in the clinic, why they enrolled and what contraceptive methods they received, and their continuation with the clinic. Chi-square analysis and Student's t-tests were used to test for significant differences between the two school and sex groups. Life table and regression techniques were employed to examine clinic continuation. The main findings are teens of both sexes used the clinic, and junior high males used it in surprisingly large numbers; there were no major school or sex differences in the characteristics of those who enrolled; most students enrolled to obtain a contraceptive method; although many females served by the clinic had previously used another family planning clinic, the majority of them had unmet needs; the rate of clinic continuation was high; and certain factors contributed to clinic continuation. These findings suggest that a clinic in a school-linked setting can successfully attract students to use its services and it may offer certain advantages for reaching sexually active teens in search of contraceptive protection. PMID- 3108950 TI - Multiple cause-of-death analysis of hypertension-related mortality in New York State. AB - Multiple cause-of-death data--that is, records of all medical conditions listed on death certificates--are used to study hypertension mortality in New York State during 1968-82. Mortality rates based on underlying causes for ischemic heart disease (IHD) and stroke are selected for comparison. During 1968-78, white women showed the largest age-adjusted decline of all race-sex groups for hypertension, as white men did for stroke and nonwhite men did for IHD. White men showed the largest age-adjusted decline for all three diseases for 1979-82. In general, declines in hypertension death rates are more comparable to declines in stroke mortality than to IHD mortality. PMID- 3108949 TI - Effects of community characteristics on young physicians' decisions regarding rural practice. AB - The supply of physicians has increased rapidly during the past decade. To examine the impact of this expanding supply on the geographic distribution of physicians in rural areas, we examined the location patterns of 1974-78 medical school graduates practicing in 1983 in rural areas. Of 2,112 rural counties, 58 percent gained at least one 1974-78 graduate; 31 percent of the least populous rural counties gained physicians; and 92 percent of most populous counties gained physicians. When Health Manpower Shortage Areas were examined separately, it was found that only 45 percent of the HMSAs that consisted of an entire county gained a young physician compared with 61 percent of non-HMSA counties. Characteristics of counties that gained a young physician were compared with characteristics of counties that did not attract a young physician. Results of the multivariate analysis indicated that the probability that a county would attract a young physician is positively related to population, the supply of physicians, the proportion of white collar employment, and the presence of a college. Higher levels of farm population are associated with a lower probability that a county would attract a young physician. These findings suggest that diffusion of young physicians into rural areas is occurring as the supply of physicians increases. However, young physicians are attracted to communities with particular characteristics. Those counties with fewer attractive characteristics may continue to have difficulty gaining physicians to serve their communities. PMID- 3108951 TI - Use of antiepileptic drugs in the elderly population. AB - Medical records for 572 patients in two extended care facilities were reviewed to study seizure disorders and antiepileptic drug use. Seventy patients (12.2 percent) were receiving antiepileptic drugs. Of this group, 43 patients (61.4 percent) had a diagnosis of epilepsy or documented seizures, 2 were being treated for neuralgia, and 25 (35.7 percent) had no reason given for antiepileptic use. The most common cause was cerebrovascular accident (38.9 percent), and no associated etiology was found in 29.2 percent. Phenytoin was the most commonly used agent. Thirty-two (45.7 percent) were taking two or more antiepileptic drugs. Thirteen patients had had no serum concentration monitoring in the last year. Thirty-seven patients (52.9 percent) had had at least one serum concentration outside of the therapeutic range. PMID- 3108952 TI - Parenteral hyperalimentation. PMID- 3108953 TI - The synergistic effect of aphidicolin on the yield of X-ray-induced chromosome aberrations throughout the cell cycle in JU56 cells. AB - The effect of a 2-h post-treatment with aphidicolin at a dose sufficient to inhibit DNA synthesis on the yield of X-ray-induced chromosomal aberrations throughout the cell cycle was measured. Exposure to aphidicolin during and after irradiation brought about an increase in exchanges in cells irradiated in G2, in sister unions only in cells irradiated in S, and in all chromosome aberration types (fragments, sister unions, and dicentrics) in cells irradiated in G1. It is suggested that, during G1 and G2 but not during S inhibiting the repair enzyme alpha-polymerase brings about the conversion of some X-ray-induced DNA lesions to double-strand which can then take part in aberrations. PMID- 3108954 TI - [MR tomography in parenchymatous neurocysticercosis]. AB - MRI-findings in a case of parenchymal neurocysticercosis are presented. The changes of the lesions as a response to chemotherapy were monitored by MRI and CT. Problems of sensitivity (MRI vs. CT) and MRI differential diagnoses are discussed. PMID- 3108955 TI - Suprasellar germinoma: radiation therapy. AB - From 1974 to 1984, nine patients with suprasellar germinoma were treated with megavoltage radiation therapy. The entire craniospinal axis was irradiated in all patients, with median doses of 45.6 Gy, 31.6 Gy, and 25.2 Gy delivered to the tumor volume, whole brain, and spinal cord, respectively. Two patients have died (14, 11.5 months) without evidence of tumor: one of uncontrolled endocrine dysfunction due to patient noncompliance, the other of hyperosmolar coma. There have been no tumor recurrences with a median 68-month follow-up among seven survivors. The dose usually recommended for treatment of intracranial germinoma is 50-55 Gy. Our data suggest that 45 Gy may be sufficient, if treatment volume is adequate. Posttherapy endocrine testing is also essential. PMID- 3108956 TI - Cochlear implant candidates: assessment with CT and MR imaging. AB - Eighty-seven patients with severe to profound hearing loss were evaluated for possible placement of a multichannel cochlear implant hearing device. After initial clinical screening, 42 patients underwent computed tomographic (CT) examination. Five of these patients were also examined with magnetic resonance (MR) imaging. Twenty-two patients received implants. CT of the middle and inner ear was normal in 24 patients (57.1%) and showed labyrinthine ossification in 12 (28.6%), cochlear or fenestral otosclerosis (or both) in four (9.5%), and congenital cochlear malformation in two (4.8%). The information provided by CT was used to (a) exclude patients in whom multichannel cochlear implantation would most likely be unsuccessful (owing to obliterative labyrinthine ossification, or congenital cochlear malformation, severe cochlear, or fenestral otosclerosis), (b) help select the best ear for implantation, and (c) provide a preoperative picture of normal variants and avoidable surgical pitfalls. MR experience is limited but assessment of the size of the cochlear nerve and the membranous labyrinth is possible with this modality and may provide additional information in the evaluation of these patients. PMID- 3108957 TI - The interstitial nucleus of Cajal and its role in the control of movements of head and eyes. PMID- 3108959 TI - Inhibition of leukotriene-induced contraction of guinea pig trachea by 5 lipoxygenase inhibitors. AB - The effects of the 5-lipoxygenase inhibitors nordihydroguiaretic acid (NDGA), 5, 8, 11, 14-eicosatetraynoic acid (ETYA), 1-phenyl-3-pyrazolidone (phenidone) and BW-755c, on the contractile response to LTC4 or LTD4 were examined on the isolated guinea pig trachea. Responses to either LTC4 or LTD4 were obtained on indomethacin treated tissues, in the presence of either L-serine-borate complex or L-cysteine, respectively, to inhibit metabolic conversion of the leukotrienes. NDGA (30 microM) and ETYA (100 microM) produced a selective competitive antagonism of LTD4-induced contractions, while phenidone antagonized both LTC4- and LTD4-induced responses in a non-competitive manner. In contrast, BW-755c (30 microM) did not significantly antagonize LTC4 or LTD4 concentration-response curves. The results suggest that leukotriene antagonism may be produced by large concentrations of some 5-lipoxygenase inhibitors. PMID- 3108958 TI - Effects of hydrocortisone, oestradiol and progesterone on A23187-stimulated prostaglandin output from the guinea-pig uterus superfused in vitro. AB - Hydrocortisone (10 micrograms/ml) had no effect on the basal outputs and A23187 stimulated outputs of PGF2 alpha, PGE2 and 6-keto-PGF1 alpha from the Day 15 guinea-pig uterus superfused in vitro. These findings indicate that the high output of PGF2 alpha from the guinea-pig uterus during the last one-third of the oestrous cycle is not modulated by the adrenal glucocorticoid hormones. Progesterone (10 micrograms/ml) had no effect on the A23187-induced increases in PG output from the Day 15 guinea-pig uterus. However, oestradiol (10 micrograms/ml but not 1 microgram/ml) significantly reduced the increases in outputs of PGF2 alpha, PGE2 and 6-keto-PGF1 alpha induced by A23187 from the Day 15 guinea-pig uterus, without affecting basal PG outputs. The increase in uterine tone induced by A23187 in the Day 15 guinea-pig uterus was reduced by 20-50% by oestradiol (10 micrograms/ml). The addition of oestradiol (10 micrograms/ml) and progesterone together (10 micrograms/ml) produced the same effects on the Day 15 guinea-pig uterus as oestradiol alone. Oestradiol (10 micrograms/ml) also reduced the A23187-induced increases in PG output from the Day 7 guinea-pig uterus, but did not reduce the increase in uterine tone. Oestradiol (10 micrograms/ml) reduced the increases in outputs of PGF2 alpha, PGE2 and 6-keto-PGF1 alpha induced by exogenous arachidonic acid from the Day 7 and Day 15 guinea-pig uterus. Previous studies have shown that oestradiol is not a cyclo-oxygenase inhibitor. The present findings suggest that oestradiol, at a relatively high concentration, may interfere with the access of arachidonic acid to the cyclo oxygenase enzyme. This action of oestradiol may explain its anti-luteolytic action when administered to guinea-pigs in large doses after Day 9 of the cycle. PMID- 3108960 TI - Salvage of ischemic rabbit ear by BW-755C and steroids, but not by indomethacin. AB - The effects of anti-inflammatory steroids and BW-755C (both of which inhibit the formation of prostaglandins and leukotrienes) were studied in ischemia-induced edema and necrosis of the rabbit ear utilizing an occlusion reperfusion model. The results were compared with cyclooxygenase inhibitors which selectively block the synthesis of prostaglandins without affecting leukotriene production. Significant inhibition of the progression of necrosis was observed with both methyl prednisolone and BW-755C. The cyclooxygenase inhibitors, naproxen and low dose indomethacin had no effect on the progression of ear necrosis. By contrast, high-dose indomethacin significantly inhibited edema but accelerated the progression of necrosis. PMID- 3108961 TI - Kinetic studies on the inactivation of 5-lipoxygenase by 5(S) hydroperoxyeicosatetraenoic acid. AB - The oxygenation of arachidonic acid (AA) by guinea-pig neutrophil 5-lipoxygenase terminates prematurely at a substrate utilization of only 50%. In the presence of dithiothreitol (DTT), reaction progress continues longer but still terminates prematurely, at about 70% substrate turnover. The addition of more substrate during the first 60 seconds of the initial reaction resulted in continued product formation. However, at times after 120 seconds, the addition of more AA could not produce additional product formation. Together, these results indicate a time dependent (t1/2 = 0.5-1.0 min), irreversible loss of enzyme activity. To determine if the product 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid (5-HPETE) mediates the inactivation, it was tested for its ability to irreversibly inhibit the enzyme and found to inactivate 5-lipoxygenase with Ki = 0.05 +/- 0.01 microM and ki = 1.4 +/- 0.4 min-1. DTT changed the apparent affinity of 5-HPETE (Ki = 0.33 +/- 0.09 microM) but had no effect on the rate of inactivation (ki = 1.26 +/ 0.62 min-1). In contrast, the hydroxy derivative of 5-HPETE, 5-hydroxy-6,8,11,14 eicosatetraenoic acid (5-HETE), is a reversible, time-independent inhibitor with Ki = 6.3 +/- 0.9 microM regardless of DTT. The ability of thiols to protect 5 lipoxygenase from production inactivation is due, at least in part, to a non enzymatic reaction between DTT and 5-HPETE that converts the hydroperoxy acid to a material that can no longer inactivate the enzyme. PMID- 3108962 TI - Decreased pulmonary vascular responsiveness in rats raised on an essential fatty acid deficient diet. AB - Leukotriene C4 is produced during hypoxic pulmonary vasoconstriction and leukotriene inhibitors preferentially inhibit the hypoxic pressor response in rats. If lipoxygenase products are important in hypoxic vasoconstriction, then an animal deficient in arachidonic acid should have a blunted hypoxic pressor response. We investigated if vascular responsiveness was decreased in vascular rings and isolated perfused lungs from rats raised on an essential fatty acid deficient diet (EFAD) compared to rats raised on a normal diet. Rats raised on the EFAD diet had decreased esterified plasma arachidonic acid and increased 5-, 8-, 11-eicosatrienoic acid compared to rats raised on the normal diet (control). Compared to the time matched responses in control isolated perfused lungs the pressor responses to angiotensin II and alveolar hypoxia were blunted in lungs from the arachidonate deficient rats. This decreased pulmonary vascular responsiveness was not affected by the addition of indomethacin or arachidonic acid to the lung perfusate. Similarly, the pulmonary artery rings from arachidonate deficient rats demonstrated decreased reactivity to norepinephrine compared to rings from control rats. In contrast, the tension increases to norepinephrine were greater in aortic rings from the arachidonate deficient rats compared to control. Stimulated lung tissue from the arachidonate deficient animals produced less slow reacting substance and platelet activating factor like material but the same amount of 6-keto-PGF1 alpha and TXB2 compared to control lungs. Thus there is an association between altered vascular responsiveness and impairment of stimulated production of slow reacting substance and platelet activating factor like material in rats raised on an EFAD diet. PMID- 3108963 TI - Pharmacological comparison of L-serine borate and glutathione as inhibitors of metabolism of LTC4 to LTD4 by the isolated guinea pig trachea. AB - Cumulative dose-response curves to leukotriene C4 (LTC4) and leukotriene D4 (LTD)4 were obtained on indomethacin (5 microM) treated isolated guinea pig tracheal spiral strips. LTC4 curves, in the presence of either glutathione (GSH; 10 mM) or L-serine borate (SB; 45 mM), were not antagonized by FPL-55712 (3 microM), a selective LTD4 receptor antagonist. LTC4 curves on trachea treated with a lower concentration of GSH (1 mM), and LTD4 curves were competitively antagonized by FPL-55712. LTC4 curves on GSH (10 mM) treated trachea were 2 fold to the left of those on SB treated tissues. This effect of GSH was blocked by pretreatment with nordihydroguiaretic acid (30 microM), an inhibitor of 5 lipoxygenase. GSH (10 mM) and SB (45 mM) are effective inhibitors of conversion of LTC4 into functionally important levels of LTD4 by the guinea pig trachea. In addition, GSH appears to enhance LTC4 responsiveness by increasing synthesis of a contractile 5-lipoxygenase product(s), possibly LTC4. From the data it is suggested that for inhibition of LTC4 metabolism, SB may be more useful when examining responses to exogenously applied LTC4, while GSH (10 mM) may be more useful when examining responses to endogenously generated LTC4. PMID- 3108964 TI - Alterations of vascular prostacyclin and thromboxane A2 in Dahl genetical strain susceptible to salt-induced hypertension. AB - To assess the implications of vascular eicosanoids system in the hypertension of Dahl salt-sensitive (Dahl S) strain, we investigated the production of vascular vasodepressor and vasoconstrictor eicosanoids in Dahl S rats. 14-week-old Dahl S rats on a 0.11% NaCl diet (normotension) or a 0.3% NaCl diet (borderline hypertension) had a significantly lowered generation of vascular prostacyclin (PGI2), compared with Dahl salt-resistant (Dahl R) rats. The impairment of vascular PGI2 in Dahl S rats was restored to the normal level of Dahl R rats with the elevation of blood pressure induced by a high salt diet (4% NaCl). The production of vascular PGI2 was closely related to the height of blood pressure. The deterioration of vascular PGI2 was also found in 4-week-old Dahl S rats with normotension. Conversely, vascular thromboxane A2 (TXA2) was significantly enhanced in 14-week-old Dahl S rats in all of the feeding groups. Thus, it seems possible that the proved alterations of the vasodepressor and vasoconstrictor eicosanoids partially contribute to the genesis of salt hypertension. Although the exact mechanisms remain obscure, the adaptation of vascular PGI2 on a high salt diet may be suitable to compete with the high blood pressure and to protect against the vascular damage. PMID- 3108965 TI - Central nervous system action of TRH to stimulate gastric emptying in rats. AB - The effects of intracisternal injection of TRH on gastric emptying of a liquid meal was investigated in 24 h fasted rats using the phenol red method. Intracisternal injection of TRH, RX 77368, or [N-Val2]-TRH, an analog devoid of TSH-releasing activity, 5 min prior to a meal, stimulated gastric emptying measured 20 min later. TRH action was dose dependent (1-100 ng), and rapid in onset. The calculated time for emptying half of the meal was decreased from 16 +/ 3 min (control group) to 4 +/- 1 min (TRH 30 ng). The stable analog, RX 77368, unlike TRH, stimulated gastric emptying when the meal was given 60 min after peptide injection. Intravenous injection of atropine (2.5 micrograms) inhibited and that of carbachol (1 microgram) stimulated gastric emptying whereas i.v. injection of TRH (0.1-1 microgram) had no effect. Vagotomy but not adrenalectomy reversed the increase in gastric emptying induced by intracisternal TRH. Atropine blocked the stimulatory effect of TRH and carbachol. These results demonstrate that TRH acts within the brain to stimulate gastric emptying through vagus dependent and cholinergic pathways whereas alterations of adrenal and pituitary thyroid secretion do not play an important role. PMID- 3108966 TI - [Nutritional evaluation in hospitalized infants]. PMID- 3108967 TI - [Sensitivity of 3 criteria of nutritional evaluation for the diagnosis of malnutrition in infants]. PMID- 3108968 TI - [Epidemiology of bovine brucellosis in tropical Africa. II. Serological analysis and identification of the first two strains of Brucella abortus biotype 3 in Niger]. PMID- 3108969 TI - [Incidence of sarcosporidia in cattle in Shaba (Zaire)]. PMID- 3108970 TI - [Use of immunoglobulin fraction S-7 in the preoperative stabilization of a patient with myasthenia gravis]. PMID- 3108971 TI - [Heart-lung transplantation]. AB - The combined transplantation of heart and lungs, first done successfully by the Stanford Team (USA) in 1982, at present seems to be superseding lung transplantation alone, and has broadened the indications of heart transplantation to include terminal heart failure with fixed pulmonary arterial hypertension. After reviewing the causes for failure in lung transplants, the authors stress the superiority of heart-lung transplants compared to isolated lung transplantations: healing of the tracheal anastomosis, ease of detection of rejects by endomyocardial biopsy and the lack of inhomogeneity of the ventilation/perfusion ratios. This operation still poses problems of surgical technique as the mediastinal nerves need to be preserved and the risk of haemorrhage linked to the mediastinal dissection or to the eventual pulmonary separation under cardiopulmonary bypass is important. Donor subjects for cardiopulmonary transplantation are rare as they ought to have a thoracic cage of matching size to the recipient and to be free of pulmonary infection and trauma. The post-operative complications are essentially those of immediate haemorrhage, graft rejection, pulmonary oedema and infection. The late complications are coronary atherosclerosis and bronchiolitis obliterans. The indications of such a transplant are currently reserved for primary or secondary pulmonary hypertension and to respiratory failure with a normal thoracic cage and ventilatory mechanics. PMID- 3108972 TI - [Effects of TRH and secretin on serum output of immunoreactive trypsin: evidence of a direct inhibitory mechanism]. PMID- 3108973 TI - [Thyrotropin hyperresponsiveness and antithyroid antibodies in clinically euthyroid postpubertal thalassemic patients]. PMID- 3108974 TI - [Immunoradiometric determination of plasma TSH in the evaluation of thyrotropin suppression in subjects with hyperthyroidism]. PMID- 3108975 TI - [Microencapsulation of living cells and tissues. Theoretical and practical aspects]. PMID- 3108976 TI - Projected benefits and risks from mammographic screening. PMID- 3108977 TI - Prospective payment and patient acuity levels. PMID- 3108978 TI - Variations of intestinal calcium absorption in adult frogs (Rana esculenta). Effect of lysine. AB - Intestinal calcium absorption was investigated in an adult frog (Rana esculenta) by injecting a CaCl2 solution containing 45Ca into the lumen. The 45Ca absorption coefficient in the proximal loop was higher than in the distal loop, only when the CaCl2 solution was left for 4 h. This coefficient increased both in the proximal and distal loops when a 4-h treatment was substituted for a 1-h treatment. The coefficient increased in the whole intestine during the first 2 h of treatment (1 h: 21%; 2 h: 55%) and remained stable afterwards in our experimental conditions. The intestinal calcium absorption increase occurred early in the presence of L-lysine (100 mM), since the coefficient already reached its maximum value (52%) after a 1-h treatment. PMID- 3108979 TI - Purification of three fragments of the dermonecrotic toxin from Pasteurella multocida. AB - Dermonecrotic toxin purified from sonicates of Pasteurella multocida was mildly trypsinized. The trypsinized preparations were reversibly dissociated into three polypeptides, with molecular weights of about 23,000 (fragment a), about 64,000 (fragment b), and about 74,000 (fragment c) by treatment with 100 mM dithiothreitol and 6 M urea. Upon removal of dithiothreitol and urea from the dissociated toxin by dialysis, the fragments reassociated and formed dermonecrotic toxin indistinguishable from the native toxin. The three fragments were separated from the dissociated toxin by gel filtration on a Sephadex G-200 column equilibrated with buffer containing 4 M urea and 1 mM dithiothreitol. The purified fragments a, b, and c did not show dermonecrotic activity for guinea pigs. Immunodiffusion and immunoelectrophoretic analysis with rabbit anti dermonecrotic antiserum showed that the three purified fragments were antigenically distinct but had partial identity with the native toxin. PMID- 3108980 TI - Sources of error and variability in the determination of anaerobic threshold in healthy humans. AB - The derivation of anaerobic threshold (AT) from the ventilatory responses to incremental exercise is associated with several sources of variability including true biological variability and the error attributable to the observer interpretation of data. To define and quantitate the sources of variability in AT determination we exercised 6 healthy volunteers 6 times and submitted plots of ventilation (Ve), CO2 production (VCO2), respiratory exchange ratio (R) and the ventilatory equivalent for oxygen (Ve/VO2) in random order to 4 independent observers. Within-subject variability in AT ranged from 7 to 55% depending on the subject, ventilatory parameter and observer with an overall mean coefficient of variability of 24%. Significant day-to-day variability was demonstrated in 4 of the 6 subjects using AT values derived from at least one of the ventilatory parameters (Anova, p less than 0.05-p less than 0.001). Mean values for AT obtained with the Ve and VCO2 plots (1.91 and 1.69 liter/min VO2) were significantly lower than those obtained from R and Ve/VO2 plots (2.28 and 2.6 liters/min VO2; p less than 0.001, Anova). Anova showed significant differences in AT values derived by one of the observers compared to the other three (p less than 0.001). A significant observer/ventilation parameter interaction was also found (p less than 0.001) due to one observer consistently estimating higher values of AT from the R plots. The observer error in deriving AT from each exercise test using the Ve plots = 24%, for VCO2 = 19% for R = 29% and for Ve/VO2 = 15%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3108981 TI - Effect on spirometry of distilled water and cromoglycate solutions nebulised by a small portable ultrasonic nebuliser. AB - The airway response to inhaled ultrasonically nebulised distilled water and three disodium cromoglycate solutions (DSCG in distilled water, normal saline and buffered saline) produced by a small portable nebuliser was determined by spirometry in 12 stable adult asthmatics in a double-blind trial. The mean percentage falls in forced expiratory volume in 1s (FEV1) were 13.4% following distilled water, 5.6% following DSCG in distilled water, 4.8% following DSCG in normal saline, 6.9% after DSCG in buffered saline. The fall in FEV1 was significantly greater (p less than 0.01) after distilled water than after all DSCG solutions with no significant difference between the DSCG solutions. Coughing was also greater during inhalation of nebulised distilled water than during inhalation of nebulised DSCG solutions (p less than 0.01). PMID- 3108983 TI - High serum levels of soluble interleukin-2 receptors in sarcoidosis. AB - We provide evidence that high levels of soluble interleukin-2 receptor (sIL-2R) are present in the serum of patients with sarcoidosis. Because sIL-2R is capable of binding to its ligand (IL-2), the increased serum levels of this molecule could induce a starvation of IL-2. This mechanism could help to explain a number of immunological abnormalities extensively reported in these patients and generally attributed to not yet identified serum inhibitory factors. PMID- 3108982 TI - [Clinical usefulness of a transdermal nitroglycerin patch as a sustained vasodilator for patients with heart failure]. PMID- 3108984 TI - Serum cortisol levels in clinically normal feedlot lambs and clinicopathological features of septicemic pasteurellosis. PMID- 3108985 TI - [Importance of Chagas disease in Mexico]. PMID- 3108986 TI - Pyocin types of clinical strains of Pseudomonas aeruginosa isolated in Morelia, Mexico (1980-1984). PMID- 3108987 TI - [The impact of genetic engineering in hemorrhagic and thrombotic diseases]. PMID- 3108988 TI - [Long-term patients and the role of the geriatric service of the regional hospital]. PMID- 3108989 TI - [Selective thrombolysis of clots: effect of tissue-type plasminogen activator in the treatment of thromboembolic diseases]. PMID- 3108990 TI - Classics in infectious diseases. On the antiseptic principle of the practice of surgery. By Joseph Lister. PMID- 3108991 TI - [Anorexia nervosa: a clinical review of 12 cases]. PMID- 3108992 TI - [Occurrence of non-A, non-B post-transfusion hepatitis in heart surgery. Prospective study on the value of the determination of serum alanine aminotransferase and detection of anti-HBc antibodies in blood donors]. AB - We studied a group of 64 patients undergoing cardiac surgery for the occurrence of post-transfusion hepatitis during a follow-up period of 5 months. They received blood units (packed red cells in saline-adenine-glucose medium and/or fresh frozen plasma exclusively) from 447 volunteer donors. Post-transfusion hepatitis was identified in 5 patients: 1 patient had cytomegalovirus hepatitis and the remaining 4 cases were defined, by exclusion, as non-A, non-B hepatitis (with prevalence and incidence rates of 80% and 6.25% respectively). We found no statistically significant differences between the numbers of transfused blood product units in patients who developed non-A, non-B hepatitis as compared to those who did not. Our analysis of the predictive effectiveness of alanine aminotransferase and anti-HBc antibodies screening in blood donors to prevent non A, non-B post-transfusion hepatitis led to the following conclusions: we failed to confirm the association between anti-HBc in blood donors and enhanced risk of non-A, non-B hepatitis in recipients since no case developed among patients receiving blood products from anti-HBc positive donors. So, 20 donors (4.5%) would have been discarded without any reduction of the incidence of non-A, non-B hepatitis. we could not confirm nor exclude the possibility that screening donor blood for elevated alanine aminotransferase levels would have reduced the number of non-A, non-B hepatitis in recipients. PMID- 3108993 TI - [Experimental and preliminary observation on the ultimate influence of cyclosporin on chronic infection of mice by Trypanosoma cruzi]. PMID- 3108994 TI - [Enteric fevers during the period 1976-1985 in Romania. Observations with practical implications]. PMID- 3108995 TI - [Efficacy of influenza vaccination in an industrial collective in the municipality of Bucharest during the 1985-1986 influenza season]. PMID- 3108996 TI - A comparative study of the immunoantigenicity of eight Paracoccidioides brasiliensis isolates. PMID- 3108997 TI - [Mollusca of the genus Biomphalaria from Minas Gerais, in relation to host parasite adaptation and importance in the epidemiology of schistosomiasis]. PMID- 3108998 TI - Anti-T (Thomsen-Friedenreich) agglutinin in Chagas' disease. PMID- 3108999 TI - Changes of rabbit pulmonary elastic properties and bronchomotricity in experimentally induced chronic Chagas' disease. PMID- 3109000 TI - Double-blind therapeutical evaluation based on the quantitative oogram technique, comparing praziquantel and oxamniquine in human schistosomiasis mansoni. PMID- 3109001 TI - The paradox of DRGs. PMID- 3109002 TI - Some thoughts on long-term care. PMID- 3109003 TI - Autometallographic demonstration of gold in human fetal liver and placenta. PMID- 3109004 TI - Immunology of tuberculosis: new directions in research. AB - Tuberculosis is still one of the major health problems in almost all over the world. Thus, new directions in basic and applied research on tuberculosis are under investigation. In this review we have provided recent data obtained in our laboratories on three main aspects of the immunology of tuberculosis, namely: i. the role of B lymphocytes in the processing and presentation of Mycobacterium tuberculosis antigens to T cells; ii. the activation and characterization of mycobacterial-specific T cell clones; iii. the T cell regulation of the immune response to M. tuberculosis. The analysis of the antigenic determinants of M. tuberculosis relevant in the antimycobacterial immunity is the major goal of the WHO programme on the immunology of tuberculosis. In fact, the attempt to develop a second generation vaccine against this microorganism is now possible by analyzing recombinant genomic DNA libraries of M. tuberculosis with monoclonal antibodies and T cell clones. In the near future, the identification of epitopes recognized by mycobacterial-specific T cells with helper, cytotoxic and suppressor functions will allow the preparation of recombinant and synthetic vaccines effective in the control of this disease. PMID- 3109005 TI - C8 beta subunit deficiency in a patient with recurrent neisserial infections. AB - A 15-year-old woman with a history of recurrent episodes of meningococcal infections was admitted to our hospital with signs and symptoms indicating a meningeal inflammation. Since in the last few years some of the patients affected by recurrent meningococcal infections have been recognized to have selective complement deficiencies, the patient's serum was studied for determining the complement function. C8 was found to be present only in traces, with a pattern of partial identity as compared with that of the normal human serum. Moreover, total hemolytic complement was undetectable and could be completely restored with purified C8, but not with other complement components; thus, we concluded for the presence of a C8 deficiency state. Further reconstitution experiments carried out with sera having selective deficiencies of either C8 beta or C8 alpha-gamma subunits allowed us to recognize the presence of a dysfunctional C8 molecule lacking the beta chain, but possessing the alpha-gamma subunit. The clinical history of the patient, characterized by recurrent meningococcal infections, further supports the current concept of an increased susceptibility of the C8 beta-deficient patients to Neisseria meningitidis infections. PMID- 3109007 TI - The serotonergic system in Tetrahymena pyriformis. AB - Assays were performed to determine the presence of serotonin (5 hydroxytryptamine) in Tetrahymena pyriformis GL in two different media using two different assay procedures. Serotonin was present in quantities consistent with those observed in other varieties of protozoa. The serotonin metabolite 5 hydroxyindoleacetic acid (5-HIAA) was also present, suggesting that the enzyme, monoamine oxidase (MAO), provides for serotonin deamination. Inhibition of MAO in Tetrahymena was apparent due to resulting accumulation of serotonin and decreased levels of 5-HIAA. The data suggest that serotonin mediates a functional role in Tetrahymena pyriformis GL and that its metabolism may be relevant to such functions. PMID- 3109006 TI - Association between lupus anticoagulant and epilepsy. AB - Lupus anticoagulant associated with thrombocytopenia, thrombosis or recurrent abortions was diagnosed in 2 epileptic patients chronically treated with anticonvulsant drugs. The immunoglobulin fractions containing the anticoagulant activity were isolated and characterized. A search for lupus inhibitor was carried out in 96 consecutively examined patients, but no further cases were found. Although rarely, lupus anticoagulant and epilepsy may be associated. Whether lupus anticoagulant is causally related with epileptic seizures or secondary to the use of antiepileptic drugs remains to be established. PMID- 3109008 TI - [Enteral feeding: principles and applications]. PMID- 3109009 TI - [Polychlorobiphenyl residue levels in edible marine Mollusca, Crustacea and Cephalopoda]. PMID- 3109010 TI - [Spondylarthropathies or ossifying polyenthesitis. Scintigraphic and scanographic evidence]. AB - Ossifying enthesites present an undeniable diagnostic value in every chronic inflammatory rheumatism at an early stage, not only in adults but also in children. Bony scintigraphy discovers them in most localizations at a preradiological stage, as soon as they cause pain. The scanner examination enables to follow the anatomical evolution of the ossifications. It is perfectly suitable for the study of sacro-iliac and interapophyseal joints. Ossifying enthesites, the evolution of which spreads over several years, often depend on mechanical, professional or athletic constraints. Ossifying enthesitis is a common characteristics of "classic" spondylo-arthropathies which are all ossifying polyenthesites: ankylosing spondylarthritis, psoriasic rheumatism, rheumatism of enteropathies, Fiessinger-Leroy-Reiter syndrome and juvenile spondylo-arthropathies. PMID- 3109011 TI - [Planorbid survey in the State of Sao Paulo: 6th Administrative Region]. PMID- 3109013 TI - [8 cases of African noma. The therapeutic importance of nutrition]. AB - Eight cases of noma observed in black Africa included five children examined during the first few days of the affection. They were aged between 4 and 5 years and had energy, protein and vitamin (pre-kwashiorkor) deficiency. Spontaneous recovery is possible if the nutritional lack is corrected immediately. PMID- 3109012 TI - [Schistosomiasis mansoni in experimentally malnourished mice]. PMID- 3109014 TI - [Comparison of the effect of 11 antianginal drugs (double-blind crossover study)]. PMID- 3109015 TI - On the mechanism of biosynthesis of cholestanol from 7 alpha-hydroxycholesterol. AB - In a patient with cerebrotendinous xanthomatosis (CTX), a small part of i.v. administered [7 beta-3H]-7 alpha-hydroxycholesterol was converted into cholestanol. Traces of 3H were also found in plasma cholesterol, but its specific radioactivity was only about 1% of that of cholestanol. When [7 beta-3H]-7 alpha hydroxycholesterol was given orally to rabbits, significant amounts of 3H were found in cholestanol in different organs. Much less 3H was found in cholesterol. Our results support the conclusion that the pathway from 7 alpha hydroxycholesterol to cholestanol does not involve cholesterol, but 7 alpha hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one as intermediates. PMID- 3109017 TI - Enprostil and cimetidine: comparative efficacy and safety in patients with duodenal ulcer. AB - The safety and efficacy of enprostil, 35 micrograms twice daily, and of cimetidine, 400 mg twice daily, in the treatment of duodenal ulcers were compared in a randomized, double-blind, parallel, multiclinic study. Endoscopy was performed before treatment and at 2-week intervals for 6 weeks or until the ulcer healed. Patients recorded their drug compliance, antacid use, ulcer symptoms, and adverse experiences daily. One hundred and six patients entered the trial, of which 104 were eligible for the initial endoscopy analysis. Base-line characteristics were similar in the two treatment groups. The cumulative healing rates in the enprostil group were 56%, 86%, and 92% at 2, 4, and 6 weeks, respectively, and those in the cimetidine group were 53%, 84%, and 90% (NS). The healing rates for nonsmokers at 6 weeks were 96% in the enprostil group and 97% in the cimetidine group, which were significantly greater than those for smokers- 88% and 81%, respectively. There were no significant differences in the duration, severity, or frequency of daytime or nighttime pain between the groups. Seventeen of the enprostil patients (32%) reported 21 adverse experiences during the trial, and 20 of the cimetidine patients (39%) reported 23 adverse experiences. No patients withdrew because of adverse experiences. The two drugs were similarly safe and effective in the treatment of duodenal ulcer. PMID- 3109018 TI - [An environmental sample bank for human organ samples in Munster--hair analyses]. PMID- 3109016 TI - High resolution two-dimensional protein electrophoresis in clinical chemistry. AB - High resolution two-dimensional (2D)-electrophoresis has been developed to the stage that it is possible to resolve several thousand proteins in cells and tissue, and over six-hundred proteins are separated in human serum. The 2D technique has been applied to analyses of serum from patients with multiple myeloma, macroglobulinemia and other gammopathies, and to separate apolipoproteins and study abnormalities and polymorphism of these proteins. Cerebrospinal fluid from patients with various neurological diseases has been studied by 2D-electrophoresis and seems to yield information on multiple sclerosis. The 2D-technique has been applied to normal and malignant cells and biopsies, and offers a possibility to detect disease-related proteins. Protein spots from 2D-gels may be used to raise monoclonal antibodies which subsequently can be used to develop simple clinical chemical tests for disease markers. The 2D electrophoretic method is, however, not yet suitable as a typical routine analysis in the clinical chemistry laboratory, but is primarily a research tool of considerable potential. PMID- 3109019 TI - Cryoglobulinemia in primary Sjogren's syndrome: a monoclonal process. AB - Patients with primary Sjogren's syndrome have in their sera and urine free light chains or monoclonal immunoglobulins. In addition, they have mixed monoclonal (IgM kappa) cryoglobulinemia, which is associated with extraglandular disease and greater incidence of autoantibodies. In the present study, it is demonstrated by a high resolution agarose gel electrophoresis, combined with immunofixation, that nine patients with primary Sjogren's syndrome have mixed monoclonal (IgM kappa) cryoglobulins, in contrast to those observed in five patients with secondary Sjogren's syndrome (Sjogren's syndrome and rheumatoid arthritis), 13 patients with rheumatoid arthritis and six patients with systemic lupus erythematosus, which were mixed polyclonal. PMID- 3109020 TI - Lymphoma in Sjogren's syndrome: urinary monoclonal free light chains as a diagnostic aid and a means of tumour monitoring. AB - Non Hodgkins lymphoma (NHL) is reported to be at least 40 times more common in Sjogren's syndrome (SS). Diagnosis may be difficult as blood and bone marrow haematology can remain normal, with no evidence of a serum paraprotein band or Bence-Jones proteinuria by routine electrophoresis. Using the technique of isoelectric focusing in agarose, followed by immunofixation, monoclonal free light chains can be found in the urine of 44% and 74% respectively of patients with NHL and B cell chronic lymphocytic leukaemia, but not in normal individuals. Three patients, two with typical severe primary SS and the third with several features of SS including abnormal sialography and reduced tear secretion, developed B cell NHL of parotid and/or lung. Using the above method on concentrated urine specimens, monoclonal free light chains of the same class as that demonstrated on the tumour cells were found to be present in each patient's urine. In one patient the level of urinary free light chains was monitored and found to correlate with disease activity. Using similar techniques no monoclonal light chains could be found in the urine from a further 10 cases of primary SS and 18 cases of SS secondary to rheumatoid arthritis, all of whom had no clinical evidence of lymphoma. Screening of SS patients' urine by the method described for monoclonal urinary free light chains may provide an early diagnostic clue to the development of lymphoma and be a means of tumour monitoring. PMID- 3109021 TI - Blood mononuclear cells in patients with primary Sjogren's syndrome: production of interleukins, enumeration of interleukin-2 receptors, and DNA synthesis. AB - Disturbed immunoregulation is considered an essential feature of the pathogenesis in primary Sjogren's syndrome (primary SS). After in vitro stimulation we investigated the interleukin-1 production by blood monocytes, interleukin-2 production by blood T-lymphocytes, the number of IL-2 receptor-bearing blood T lymphocytes and the blood lymphocyte DNA synthesis in 6 consecutive female patients with primary SS and in 6 female controls. In the patient group we found all the parameters examined within a wider range as compared to the controls. The three patients with reduced interleukin-2 production and low proliferative responses were exclusively characterized by elevated plasma-IgG concentration, positive antinuclear antibodies and rheumatoid factor, and by having circulating immune complexes. PMID- 3109022 TI - Characterization of a crossreactive idiotype in Sjogren's syndrome. AB - Sjogren's syndrome (SS) is characterized by lymphoid infiltration of the salivary glands and autoantibody production. Rheumatoid factor (RF) in patients with primary SS (1 degree SS) contains a crossreactive idiotype (CRI) defined by a monoclonal antibody (MoAb 17-109). This CRI was located on the kappa light chain by immunoblotting methods. A high frequency of CRI+ B cells was found in SS salivary gland biopsies, suggesting this tissue as the site of production for this autoantibody. Further characterization of CRI+ RF from SS patients was performed using antibodies prepared against synthetic peptides corresponding to the hypervariable region of RF paraproteins from patients with Waldenstrom's macroglobulinemia (WM). These results demonstrate a close structural relationship between RF in SS and WM patients. To analyze the genes that encode these RF in SS patients, B cell hybridomas that secreted CRI+ immunoglobulin were created and their DNA analyzed by Southern blot techniques. These hybridomas will allow us to determine the DNA sequence of kappa genes encoding the CRI and to identify adjacent regulatory genes that may promote high levels of CRI expression. PMID- 3109023 TI - High doses of the diphosphonate EHDP for the prevention of heterotopic ossification. An experimental and clinical study. AB - The effect of Ethane-1-Hydroxyl-1, 1-Diphosphonate (EHDP) on experimental and clinical heterotopic ossification was studied. Demineralized cortical bone matrix was implanted in the abdominal wall of three groups of adult male rats. Two groups received injections amounting to 5 and 20 mg/kg/day of EHDP, respectively, and a control group received placebo. The lower dose of EHDP had no effect on bone formation, whereas the higher dose resulted in a marked reduction in ash content and 45Ca uptake in the implants. Inhibitory effects on heterotopic bone and serum alkaline phosphatase activity were observed when treating with high doses (50 mg/kg/day) a paraplegic patient following resection of para-articular ossifications around the hips. The effect of EHDP on bone formation is interpreted as reflecting a dose-dependent interference with the deposition of hydroxyapatite crystals in the bone matrix. PMID- 3109024 TI - Subclavian flap angioplasty with absorbable suture polydioxanone (PDS). An experimental study in growing piglets. AB - The fate of the subclavian flap in aortoplasty was studied and a new synthetic monofilament, absorbable vascular suture (polydioxanone, PDS) was evaluated. In 11 piglets submitted to the aortic repair, the diameter of the aortic arch and descending aorta and the length and width of the subclavian flap were measured. The aortoplasty was performed with a continuous running suture of 6/0 PDS. All the animals survived and grew normally. They were sacrificed 6-26 weeks postoperatively, when the mentioned variables were reestimated. No aortic narrowing was found and no suture material was detectable in the lumen. The subclavian flap had grown uniformly in length and width. Histologic examination showed evening of the inner surface by intimal proliferation and healing of the anastomoses. There was no sign of flap destruction and tissue reaction to PDS suture was minimal, indicating normal growth and viability in all parts of the flap. The suture material was absorbed 26 weeks postoperatively. Continuous suture with absorbable PDS seems to be a good alternative for repair of aortic coarctation in early infancy. PMID- 3109025 TI - Scanning electron microscopic analysis of intraocular ossification in advanced retinal disease. AB - Chicken eyes from congenic blind (rd/rd) animals showing early, intermediate, and final stages of ossification, similar to the phthisis bulbi condition in man, were examined using scanning and transmission electron microscopy as well as light microscopy and X-ray microanalysis. Early stages of ossification were devoid of mineralized calcium apatite while intermediate and end stages of the disorder contained large amounts of calcium and phosphorus. This process resulted in metaplastic bone formation. An intact Bruch's membrane appeared to separate the choroid from the degenerated pigment epithelium and the developing bone suggesting that its possible origin was metaplasia of the retinal pigment epithelium and the degenerated sensory retina. The end-stage ossification resulted in "phthisic bone" formation which completely filled the vitreous cavity in a manner very similar to the human condition of phthisis bulbi. PMID- 3109026 TI - Replica-immunogold technique applied to studies on measles virus morphogenesis. AB - The replica technique was applied to studies on the dynamic process of measles virus budding on infected HeLa cells. Virus structures were identified by labeling with anti-measles antibodies and protein A-gold. The combination of these two methods enabled us to characterize the sequence of virus budding at the plasma membrane, to localize virus structures on cytoskeletons of infected cells, and to study the influence of Ca2+ ions on virus structures at the plasma membrane. Studies on platinum carbon surface replicas suggest that the process of virus budding is similar to the genesis of cellular microvilli. Replicas prepared from cytoskeletons of infected cells reveal a close association of budding virus with actin filaments composing the outer parts of the networks. Replicas of apical plasma membranes isolated from infected cells show the attachment of viral nucleocapsids to the protoplasmic membrane face of infected cells. These nucleocapsids are not present on membranes prepared from cells treated with calcium and the ionophore A23187. In addition viral cell surface antigens become randomly distributed on these cells. The data suggest that measles virus morphogenesis at the plasma membrane of cultured cells is dependent on the function of the cytoskeleton and may be influenced by Ca2+ ions. PMID- 3109027 TI - [Blood coagulation disorders]. AB - Disorders of hemostasis are frequently encountered, and, if not recognised as early as possible, in particular prior to surgery, may lead to bleeding complications which are much more difficult to treat than those where exact diagnosis permits specific preventive therapy. A first case report on a woman with an acquired inhibitor against factor VIII illustrates that even minor injury may lead to hemorrhage necessitating blood transfusion. Furthermore, as long as the defect remains inaccessible to successful substitution therapy, wound healing will not take place. A second case report describes a patient with a congenital dysfunction of blood platelets, and serves as an example for similar disorders which, if unrecognised, lead to multiple, otherwise avoidable complications. Unfortunately there is no clearcut correlation between a given defect of hemostasis and bleeding manifestations, since psychological factors, among others, appear to influence the occurrence of "spontaneous" hemorrhage. Any unexpected and unexplained bleeding complication requires careful evaluation of the possible underlying causes, since such investigations often not only affect the future of the propositus himself but also that of his family members. PMID- 3109028 TI - [Treatment of male sterility by in vitro fertilization]. AB - A pregnancy obtained through in vitro fertilization in a case of male sterility due to oligospermia with high FSH is reported. After a review of controlled studies dealing with classical andrological treatments (repair of varicocele, treatment of prostatitis and immunological sterility), the place of in vitro fertilization is evaluated in relation to intrauterine insemination using active sperm. PMID- 3109029 TI - [Occurrence and significance of Ichthyophthirius multifiliis in Switzerland]. PMID- 3109030 TI - [Leucocytozoon infections in parakeets]. PMID- 3109031 TI - South Dakota Task Force on Long Term Care and trends in geriatric medicine in South Dakota. PMID- 3109032 TI - Bipedal locomotion. AB - In the letter "Tanker 'dumping' regulations" by T. S. Wyman (5 June, p. 1160), the years of amendations to the International Convention for the Prevention of Pollution from Ships, 1973, mentioned in the second paragraph, were incorrect. The amendations were made in 1978, 1984, and 1985 (not 1987). PMID- 3109033 TI - Drug trial for Parkinson's. PMID- 3109034 TI - Corkscrew-like shortening in single smooth muscle cells. AB - The slower and more economical contraction of smooth muscle as compared to that of skeletal muscle may relate to the arrangement of its contractile apparatus. Because the arrangement of the contractile apparatus determines the manner in which a single smooth muscle cell shortens, shortening of a contracting cell was examined by tracking of marker bead movements on the cell surface by means of digital video microscopy. Smooth muscle cells were observed to freely shorten in a unique corkscrew-like fashion with a pitch of 1.4 cell lengths (that is, the length change required for one complete rotation of cell) at a rate of 27 degrees per second. Corkscrew-like shortening was interpreted in terms of a structural model in which the contractile apparatus or cytoskeleton (or both) are helically oriented within the cell. Such an arrangement of these cytoarchitectural elements may help to explain in part the contractile capabilities of smooth muscle. PMID- 3109035 TI - Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. AB - Individual protein-binding sites within the mouse immunoglobulin heavy chain and kappa light chain gene enhancers were altered, making it possible to examine the functional role of the sites during transcription. The E motifs, which bind factors that are present in many if not all cells, mostly behave as transcriptional activating sites. The only known heavy chain enhancer site that binds a lymphocyte-specific factor, the "octamer" site, plays a critical role in transcription but only in a truncated form of the enhancer. In the full enhancer, no one site is crucial because of an apparent functional redundancy. The site in the kappa enhancer that binds a factor specific to mature B cells, kappa B, was crucial to the constitutive activity of the enhancer in B cells. This factor is also inducible in pre-B cells, and the site was necessary for inducibility of the kappa enhancer. Thus, the sites defined by protein binding are important for the functional activity of immunoglobulin enhancers, with the sites that bind proteins restricted in their cellular distribution playing the most important roles. PMID- 3109036 TI - Viral hepatitis during pregnancy. PMID- 3109037 TI - Knowledge attitudes and practices in relation to schistosomiasis in a rural community. AB - A knowledge attitudes and practices survey of sanitation, water supplies and schistosomiasis was carried out in a rural schistosomiasis endemic area of Zimbabwe. Questionnaires were administered to 349 households. No latrines were present in 61% of households and information on use, likes and dislikes was collected. Most drinking water was collected from sources presenting no risk of schistosomiasis whereas most washing activities were carried out at sites presenting such a risk. Schistosomiasis was thought to be a problem in the community by over 50% of households and 79% gave haematuria as a symptom of the disease. There was a correlation between the washing site and the reported presence of schistosomiasis in the family. PMID- 3109039 TI - [Prevention of periarticular calcification using postoperative irradiation of the hip]. PMID- 3109038 TI - [The proportion of kappa and lambda light chains among monotypic IgG and IgA]. PMID- 3109040 TI - Enzyme-linked immunosorbent assay for the detection of mycobacterial antigens in the cerebrospinal fluid in tuberculous meningitis. AB - Fifty-three cerebrospinal fluid specimens from meningitis patients were investigated by enzyme-linked immunosorbent assay for detection of mycobacterial antigens. After heating at 56 degrees C for 1 hour to eliminate nonspecific interference, all 22 tuberculous meningitis (TBM) specimens had an optical density of greater than 0.05 (sensitivity 100%). Six out of 31 non-TBM cases gave false-positive results (specificity 81%). PMID- 3109041 TI - Gastric haemorrhage in a patient with neurofibromatosis. A case report. AB - A 54-year-old woman with upper gastro-intestinal haemorrhage, neurofibromatosis and an underlying schwannoma of the stomach is presented. Gastroscopy and barium meal examination revealed the presence of a submucosal gastric tumour with overlying ulceration. A Billroth II gastrectomy was performed with complete excision of the tumour; histologically this was revealed as a schwannoma of undetermined biological activity. PMID- 3109042 TI - [Von Recklinghausen neurofibromatosis and renovascular hypertension]. PMID- 3109043 TI - Esophageal motor disorders. AB - Primary esophageal motor disorders are rare, but they respond well to surgery if they are accurately diagnosed and if treatment carefully follows the fundamental principles of management. In the lower esophagus the most important primary disorders are achalasia, diffuse esophageal spasm, and scleroderma. Upper esophageal primary disorders are mostly rare; however, problems of age and neurologic diseases are a significant source of debility, making their management important. Details of investigation and management have been outlined in this article. PMID- 3109044 TI - Enteral and parenteral nutrition in patients with enteric fistulas and short bowel syndrome. AB - Significant advances in the use of enteral and parenteral nutrition in patients with either enteric fistulas or short bowel syndrome include increased usage of enteral nutrition because of its trophic effects on the gut and increased usage of both enteral and parenteral nutrition in the home setting. Current investigations are directed toward identifying gut-specific fuels and dietary and pharmacologic enhancement of nutrient utilization. PMID- 3109045 TI - [The nurse and the hemophilic adolescent in a medical boarding school]. PMID- 3109046 TI - Clinical trial of imipenem/cilastatin in severely burned and infected patients. AB - Imipenem/cilastatin was examined for safety and efficacy in a population of 20 seriously burned patients with acute bacterial infections. The study was made up of 18 males and two females with an average age of 38 years and average burn size of 52 per cent of the total body surface area. Inhalation injury was present in 14 patients. The infections treated included 16 pulmonary, two urinary tract, one wound and one bacteremia. Treatment was clinically successful in 13 patients; five patients had no improvement and the clinical response could not be determined in two in whom multisystem organ failure preceded the treated infection. All of the clinical failures were in the pulmonary infection group. No serious toxicity or side effects were noted. No patient died while receiving the drug or as a consequence of known failure of the drug. Microbiologic success was noted in 12. Resistant organisms developed in eight of whom five were in the clinical failure group. Pseudomonas aeruginosa resistant to imipenem/cilastatin was isolated from seven patients and occurred at an average of 3.6 days after treatment was begun. PMID- 3109047 TI - Endoscopic placement of feeding tubes in the critically ill patient. AB - Placement of the nasojejunal feeding tube under direct visual guidance using endoscopy offers an alternative method to those currently used. We found it to be a safe method easily performed by house staff. It is less burdensome than other described endoscopic techniques and does not require patient transfer or fluoroscopic facilities. PMID- 3109048 TI - Operations upon the biliary tract during transplantation of the liver. AB - Operation upon the biliary tract is a discipline within transplantation of the liver. There exists a background of basic science information concerning anatomy and physiology, an historical evolution of surgical techniques, a divergence of contemporary opinion regarding preferred approaches and a body of well described complications. The complication rate, once more than one-half with substantial contribution to mortality rates, now ranges from approximately 15 to 25 per cent. Current practice in most institutions is to use choledochocholedochostomy with T tube stent when a recipient duct is present and Roux-en-Y choledochojejunostomy with internal stent when a suitable recipient duct is absent. Hepatic arterial thrombosis is an important cause of complications of the biliary tract. The overlap of symptoms and signs of rejection with those of biliary sepsis and other complications of the biliary tract underscores the need for algorithmic use of diagnostic modalities in the post-transplant period. PMID- 3109049 TI - Dose reconstruction of x-ray irradiation of the larynx. AB - The authors have determined the dose distribution in the neck for parallel opposed and three field orthovoltage X-ray irradiation techniques of the larynx. LiF:Mg, Ti rods and pellets combined with film densitometry were used. Absorbed dose measured in the region of vocal chords is about 20% lower than that assessed by assuming full backscatter (perpendicular incidence) and by using standard isodose tables. PMID- 3109050 TI - [Clinically-oriented hints for the technic of integrated dosage modification in a partial irradiation field]. AB - The authors present a method allowing the application of doses differing from the reference dose in partial zones of an irradiation volume. The compensator integrated modification is performed by a simultaneous dose harmonization in the reference plane. Three methods are described by which a topographic and anatomic assignment of field and partial field is possible on the basis of the irradiation features. The optimum application of each method in the individual irradiation schemes is discussed. PMID- 3109051 TI - [Post-traumatic epilepsy]. PMID- 3109052 TI - [Long-term outlook of patients with severe craniocerebral trauma treated in Lausanne's Rehabilitation Service]. PMID- 3109053 TI - Drug resistance in Mycobacterium tuberculosis: a survey over 25 years in Blackburn. AB - Over the past 25 years the incidence of tuberculosis in Blackburn has changed from one that was below the national average to one which is consistently in the 10 highest local authority areas in England and Wales. A survey of primary and acquired drug resistance over the same period included 974 ethnic white patients and 538 of Indian subcontinent ethnic origin. Primary drug resistance in the white population has fallen consistently from 1965 onwards and is now zero. Only one case of acquired resistance has occurred in the last five years. Primary resistance in the immigrant community has been 11-15% from 1965 onwards, and five cases of acquired resistance have occurred since 1970. The pattern of drug resistance over this period supports the view that there is no evidence of cross infection between the native white and immigrant ethnic groups. PMID- 3109054 TI - Abnormal aggregation accompanies abnormal platelet Ca2+ handling in arterial thrombosis. AB - The resting levels of cytoplasmic Ca2+ (measured by Quin 2 fluorescence) and dense tubular Ca2+ (measured by chlorotetracycline, CTC, fluorescence) are shown to be higher in platelets from patients with arterial thrombosis than from normal donors. Turbidimetric studies of aggregation of diluted platelet-rich plasma (PRP) at 135 microM Ca2+ showed increased rates of aggregation for patients relative to normal controls. For ADP-stimulated aggregation, increased maximal rates (Vmax) and decreased doses for half-maximal rates were observed. With collagen-stimulated aggregation, patient samples showed only decreased ED50 values relative to normal controls. The changes in these values are linearly correlated with the elevation of resting dense tubular Ca2+ level determined by the calcium-CTC test carried out at 2 mM external Ca2+. For ADP-stimulated aggregation this relationship can be mimicked by pre-incubating normal platelets with subcritical concentrations of the Ca2+ ionophore A23187. These results suggest that elevated cytoplasmic and dense tubular Ca2+ in the "resting state" is a major factor in arterial thrombosis, rendering the platelet more sensitive to the stimulation by physiologic agents. PMID- 3109055 TI - Immunoaffinity purification of factor VIII complex. AB - Murine monoclonal antibodies to human von Willebrand factor (vWf) were immobilised on Sephacryl S-1000. Various solutes were screened for their ability to elute 125I-vWf from the immobilised antibodies. The most effective solutions were then tested to determine which allowed retention of factor VIII procoagulant activity (VIII:C) and activity of vWf measured by platelet aggregation in the presence of ristocetin (Ristocetin cofactor activity R. cof.). Finally, F VIII complex was purified from both plasma and cryoprecipitate by immunoaffinity chromatography under the selected conditions. The product had a specific activity of 45 units of VIII:C per mg of protein and 60 units of R. cof. per mg representing a 4000-fold purification from plasma. The fibrinogen and fibronectin content were each less than 4% of the total protein with vWf accounting for 60% of the total protein in the final product. Multimer analysis of the product showed a similar pattern to normal plasma and contamination by murine monoclonal antibody was less than 300 ng per mg of protein. A novel product is thus obtained containing both clinically relevant VIII:C and R. cof. in a single vial whilst using only one specific monoclonal antibody. PMID- 3109056 TI - Transplacental transfer of acquired factor VIII: C inhibitor. PMID- 3109057 TI - Substrate recognition by vitamin K-dependent carboxylase. AB - Decarboxylated osteocalcins were prepared and purified from bovine, chicken, human and monkey bones and assayed for their ability to serve as a substrate for vitamin K-dependent carboxylase from bovine liver. Substantial differences were observed, especially between bovine and monkey d-osteocalcin. Since these substrates differ only in their amino acid residues 3 and 4, it seems that these residues play a role in the recognition of a substrate by hepatic carboxylase. PMID- 3109058 TI - Sustained fibrinolysis after administration of t-PA despite its short half-life in the circulation. AB - To characterize the duration of the fibrinolytic response to tissue-type plasminogen activator (t-PA) and streptokinase (SK) in patients with acute myocardial infarction we serially assayed crosslinked fibrin degradation products (XL-FDP) and B beta 15-42 fibrinopeptide. Use of specific monoclonal antibodies permitted quantification and differentiation of fibrin from fibrinogen degradation products. Marked elevations of XL-FDP occurred within 1 hour after administration of t-PA (n = 13) or SK (n = 35) to greater than 1000 ng/ml in 79% of the patients. All patients given t-PA exhibited elevations of XL-FDP greater than 1000 ng/ml, most exhibited values greater than 5000 ng/ml (79% of patients). In contrast 6 of the patients given SK failed to exhibit XL-FDP greater than 1000 ng/ml. XL-FDP greater than 5000 ng/ml occurred in only 14%. The difference in the response to t-PA compared to SK was particularly striking 7 hours or more after administration of activator at which time XL-FDP were markedly elevated in patients given t-PA (5821 +/- 1683 ng/ml) compared with decreasing values in patients given SK (2924 +/- 1186 ng/ml) (p less than 0.01). Levels of B beta 15 42 were significantly higher after t-PA compared with SK beginning 3 hours after treatment, consistent with a greater intensity of fibrinolytic response to t-PA. Marked elevations of this short lived degradation product of fibrin (t 1/2 = 10 20 minutes) in the samples drawn late after administration of t-PA (44.3 +/- 12.8 nM) but not after SK (11.7 +/- 4.5 nM) confirmed prolonged fibrinolytic activity of plasmin after t-PA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109059 TI - Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep venous thrombosis. AB - The fibrinolytic system was investigated in 120 patients with spontaneous or recurrent deep vein thrombosis (DVT) without any known organic disease able to explain by itself the occurrence of a thrombosis and without any known defect of antithrombin III, Heparin Cofactor II, Protein C, or Protein S. The assays included: Euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator related antigen (t-PA-Ag) and plasminogen activator inhibitor activity (PA inhibitor), which were measured before and after 10 min of venous occlusion (V.O.). On the basis of the results, the patients could be classified in 3 groups: good responders with an at least two-fold increase of EFA after venous occlusion (n = 76), poor responders with a lesser increase of EFA due to deficient release of t-PA (n = 12), and poor responders with a normal t-PA release but an increased level of PA-Inhibitor (n = 32). The poor responders due to deficient t-PA release (10% of total) had a higher incidence of recurrence of deep vein thrombosis, than the other groups (p less than 0.01). An overall correlation was found between the level of PA-Inhibitor activity and the triglyceride level (r = 0.40, p less than 0.01), suggesting that these elevations may be due to a common cause, at least in some of the patients. It is concluded that a poor fibrinolytic response to venous occlusion occurs in 35 percent of DVT patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109060 TI - Increased fibrinolytic activity after surgery induced by low dose heparin. AB - Forty women undergoing surgery under general anaesthesia for hyperplasia mammae were randomized to treatment with low dose heparin (5000 IU twice daily) or not. Preoperatively, and repeated on the 3. postoperative day, assays of euglobulin clot lysis time (ELT) after venous stasis, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were performed. Compared to the control group heparin was found to give a significant rise in t-PA antigen before (24.0 vs. 11.2 ng/ml, p = 0.02), and especially after venous stasis (104.8 vs. 47.3 ng/ml, P = 0.007). t-PA activity was also significantly more increased after venous stasis in the heparin group than among the controls (4.2 vs. 1.4 U/ml, p = 0.04). This was also reflected in the ELT after venous stasis which was significantly shorter in the heparin group (p = 0.01). No differences in PAI were found between the groups. The present results point to a heparin-induced increase of t-PA synthesis in the endothelium, also giving rise to an increased level of circulating t-PA as measured immunologically. This effect of small dose heparin may play an important role in the prophylaxis against thrombo-emboli, in addition to the anticoagulant effect. PMID- 3109061 TI - Two cases of dysfibrinogenemia characterized by abnormal FPB release: fibrinogen Madrid I & II. AB - Congenital dysfibrinogenemia was found in two non related and asymptomatic families. Low levels of plasma fibrinogen were found using a chronometric assay but normal levels were found using both an immunologic method and a method to measure the fibrin formed after two hours incubation with thrombin. Kinetic analysis of fibrinopeptide release revealed a delay in the thrombin catalyzed release of fibrinopeptide B from both abnormal fibrinogens. Timed release of fibrinopeptide A was normal. Analysis of fibrinopeptides by high-performance liquid chromatography showed the same retention times in both normal and abnormal fibrinogens. Polymerisation of fibrin monomers and the sialic acid content per mol of fibrinogen were normal. Although these cases seem similar, until their structural defects are determined, it is proposed to provisionally designate them fibrinogens Madrid I & II. PMID- 3109062 TI - Tissue plasminogen activators in breast cancer. AB - Increased levels of tissue fibrinolytic activity have been detected in some malignant tumours and they have been implicated in metastatic spread. We have investigated tissue plasminogen activator (tPA) and urokinase (UK) in 26 breast carcinomas and 13 benign breast biopsies. Tissue extracts were analysed for overall fibrinolytic activity on fibrin plates and by fibrin-overlay zymography after electrophoresis on SDS-PAG. Supernatants of the extracts were analysed by an antigenic immunoassay (ELISA) and a functional bioimmunoassay (BIA) using polyclonal antibodies. Total ELISA and BIA results correlated (P less than 0.001) and all the tissues contained similar tPA levels. Malignant extracts contained significantly increased UK compared with benign extracts (1.60 +/- 0.37 iu, 0.36 +/- 0.16 iu; P less than 0.002). Zymography showed no high molecular weight inhibitor complexes and UK was almost exclusively confined to the malignant tissues (P much less than 0.02). The results suggest that malignant transformation of breast tissue is associated with the significantly increased production of UK. This may be responsible for the characteristics of malignancy or it may be a growth factor. PMID- 3109063 TI - Characteristics of a heat treated antihaemophilic cryoprecipitate. AB - In order to evaluate the influence of heat treatment (68 degrees C for 24 or 72 hours) on the essential components of antihaemophilic cryoprecipitate, i.e. factor VIII coagulant activity (VIII:C), von Willebrand factor (VIIIR:Ag and VIIIR:RCF) and fibrinogen, ordinary lyophilized cryoprecipitate was compared to heat treated, aminoacid-enriched specimens. The median reduction in factors VIII:C, VIIIR:Ag, VIIIR:RCF and fibrinogen during lyophilization of ordinary cryoprecipitate was 26 per cent, 11 per cent, 1 per cent and 8.5 per cent, respectively. Heat treatment of such cryoprecipitate resulted in 85 to 98.5 per cent reduction in these parameters, while the reduction following lyophilization and heat treatment (24 hours) of aminoacid-containing preparations was not significantly different from non-heated, ordinary cryoprecipitate. Following heating of aminoacid-enriched cryoprecipitate for 72 hours, only factor VIIIR:RCF was significantly reduced (32.5 per cent) compared to non-heated samples. Ordinary cryoprecipitate was almost insoluble following heat treatment. Enrichment with aminoacids, however, made the heat treated cryoprecipitate fully soluble, but the content of these vials were slightly slower in dissolving than non-heated preparations. Ultracentrifugation prior to lyophilization and heating did not improve the solubility. If heat treatment proves to be efficient in inactivating viral agents, we conclude that heated (68 degrees C for 24 hours), aminoacid-enriched cryoprecipitate may be a convenient product for treating haemophilia A, von Willebrand's disease and hypofibrinogenemia. PMID- 3109064 TI - A pilot study; desmopressin (DDAVP) in the treatment of deep venous thrombosis. AB - In a pilot study on 9 patients with acute deep venous thrombosis of the leg the fibrinolytic response and the possible thrombolytic effect of desmopressin (DDAVP), when given supplementary to standard heparin treatment, was examined. Six injections of 0.3-0.4 microgram DDAVP/kg b.w. at 12 hours intervals were given. No serious side effects were observed. The fibrinolytic variables that followed showed that plasma levels of t-PA increased significantly and most pronounced after the first injection. Rephlebography 4-7 days after hospitalization showed partial thrombolysis in 7 out of 9 patients. The phlebographic score according to Marder was reduced from 22.7 +/- 12.1 to 18.4 +/ 10.1 (p = 0.018), corresponding to a thrombus size reduction of 19%. No correlation between the level of the fibrinolytic variables measured and the degree of thrombolysis in the individual patients, could be demonstrated in this small number of patients. PMID- 3109065 TI - Choline plasmalogen biosynthesis by transmethylation in human platelets. PMID- 3109066 TI - Normal response to DDAVP in patients with plathology of the hypothalamoneurohypophyseal axis. PMID- 3109067 TI - Prolongation of platelet survival in hypercholesterolaemic rabbits by CGS 12970 (3-methyl-2-(3-pyridyl)-1 indoleoctanoic acid) and dazoxiben. AB - In rabbits receiving a normal laboratory diet the platelet half-life was 40.4 +/- 2.5h (mean +/- S.D., n = 35). In animals fed the cholesterol-enriched diet for 12 weeks the platelet half-life was reduced to 31.6 +/- 3.6h (mean +/- S.D., n = 35). Treatment of cholesterol-fed animals with a single daily dose of CGS 12970 (a long acting inhibitor of thromboxane synthase) normalised the platelet half life. Single daily doses of the relatively shorter acting thromboxane synthase inhibitors (CGS 13080 and dazoxiben) failed to correct the reduced platelet survival. However, twice daily dosing with dazoxiben was effective. The cyclooxygenase inhibitors, aspirin and sulphinpyrazone, failed to correct the reduced platelet survival. PMID- 3109069 TI - Platelet aggregation in human whole blood after chronic administration of aspirin. AB - We have used the impedance aggregometer to study the "ex vivo" effect of acetylsalicylic acid (ASA) in whole blood (WB) versus platelet-rich plasma (PRP) in 35 male healthy volunteers after 10 days of treatment with 25, 50, 125, 250, and 500 mg/day of ASA. Percent of inhibition of platelet aggregation was determinated at the end of treatment. A greater inhibition of platelet aggregation was observed in WB than in PRP when ASA was administrated at almost all doses. Maximal differences were at 25, 50, and 125 mg/day of ASA on adrenaline, collagen and arachidonic acid induced aggregation, and with 250 and 500 mg/day of ASA when ADP was used as aggregating agent. In the "in vitro" trials, IC-50 values of ASA on ADP and collagen induced aggregation were determined in platelet aggregation by the impedance method in both WB and PRP. ASA shows a lower IC-50 in WB than in PRP. When leucocytes were incubated in PRP samples, it effect was similar to the percent of inhibition in WB. PMID- 3109068 TI - Vascular lipoxygenase activity: synthesis of 15-hydroxyeicosatetraenoic acid from arachidonic acid by blood vessels and cultured vascular endothelial cells. AB - Although indirect pharmacologic evidence has suggested the presence of a lipoxygenase pathway of arachidonic acid (AA) metabolism in blood vessels, direct biochemical evidence has been difficult to demonstrate. We have investigated lipoxygenase metabolism in both fresh vessel preparations and cultured vascular cells from various sources and species. Lipoxygenase-derived [3H] HETE (composed of 12-HETE, 15-HETE and 5-HETE), which was abolished by ETYA but not by aspirin, was formed when [3H]AA was incubated with fresh sections of rat aorta. Lipoxygenase activity was lost following deendothelialization. A single peak of [3H] 15-HETE was produced by cultured bovine aortic and human umbilical vein endothelial cells (EC) in response to exogenous [3H]AA or from [3H]AA released by ionophore A23187 from endogenous EC membrane phospholipid pools. Cultured bovine, rabbit or rat aorta smooth muscle cells had no detectable 15-lipoxygenase activity. [14C] Linoleic acid was converted by EC to its 15-lipoxygenase metabolite, [14C] 13-hydroxyoctadecadienoic acid. These results indicate that blood vessels from different sources and species have a 15-lipoxygenase system, and this activity resides predominantly in the endothelial cells. PMID- 3109070 TI - [Fabry's disease detected by renal biopsy]. PMID- 3109071 TI - [Parenteral nutrition in newborn infants: trace elements. The Parenteral Nutrition Working Group of the Perinatology Section]. PMID- 3109072 TI - [Parenteral nutrition in newborn infants; administration of calcium, phosphate and magnesium. The Parenteral Nutrition Working Group of the Perinatology Section]. PMID- 3109073 TI - A case of liver cirrhosis complicated with endotoxemia and disseminated intravascular coagulation: a case report. AB - A 59-year-old female was admitted to our hospital because of massive ascites and increasing jaundice, suggesting a severe decompensated state of liver cirrhosis. On the third hospital day, she was diagnosed as disseminated intravascular coagulation (DIC) from a coagulofibrinolytic study and developed renal failure. Continuous drip infusion of gabexate mesilate, a synthetic inhibitor of serine protease, was found to be successful in managing DIC, followed by the restoration of renal function. During the clinical course, blood endotoxin, assayed by the chromogenic method, was initially 11 pg/ml and increased, in accordance with the elevation of serum FDP, to a level of 110 pg/ml when renal failure occurred. A proportional relationship was observed between changes in blood endotoxin and serum FDP throughout the course. This finding may be an important clue in studying the mechanism of DIC and non-septic endotoxemia both developing in liver cirrhosis. PMID- 3109074 TI - Nonlinear kinetics of inhaled propylene glycol monomethyl ether in Fischer 344 rats following single and repeated exposures. AB - The kinetics of propylene glycol monomethyl ether (PGME) and its demethylated metabolite, propylene glycol (PGLY), were investigated with the aim of describing concentration- and treatment-related changes in absorption and clearance. Groups of Fischer 344 rats received either 1 or 10 daily 6-hr inhalation exposures to PGME. Single exposures were performed using both nose-only (300, 750, 1500, and 3000 ppm) and whole-body (300 and 3000 ppm) inhalation techniques, whereas multiple exposures (300 and 3000 ppm) were confined to the whole-body procedure. PGME blood levels failed to plateau during a 6-hr inhalation exposure, indicating that absorption was limited by respiration. The clearance of PGME from the blood could be described as a pseudo-zero-order process following each exposure concentration and treatment regimen examined. PGLY blood levels indicated that the demethylation of PGME to PGLY was saturated at exposure concentrations exceeding 1500 ppm. PGME blood levels were higher in male than in female rats receiving a single 3000 ppm exposure. Unlike the results from a single exposure, PGME elimination was essentially complete 24 hr after the last of 10 consecutive 3000 ppm exposures. The changes in PGME elimination following multiple 3000 ppm exposures were associated with higher in vitro levels of cytochrome P-450 and mixed-function oxidase activity. Multiple exposures to 300 ppm did not affect PGME elimination or in vitro microsomal metabolism. PMID- 3109075 TI - Ultrastructural changes in the mouse liver induced by hepatotoxin from the freshwater cyanobacterium Microcystis aeruginosa strain 7820. AB - The time-course of ultrastructural changes was studied in mouse liver hepatocytes after i.p. injection of lethal (100 micrograms/kg) and sublethal (10 micrograms/kg) doses of the heptapeptide hepatotoxin from Microcystis aeruginosa strain 7820, a freshwater blue-green alga (cyanobacterium). At both dose levels the hepatocytes show progressive intracellular changes over time periods of 10, 20, 30, and 60 min. The changes resulting from a lethal dose were more prominent and rapid compared to those of the sublethal dose. The most common responses to lethal and sublethal doses were vesiculation of rough endoplasmic reticulum, swollen mitochondria and degranulation (partial or total loss of ribosomes from vesicles). These vesicles appear to have formed from the dilated parts of rough endoplasmic reticulum by fragmentation or separation. At the lethal dose an increased amount of whorl shaped rough endoplasmic reticulum along with large membrane-bound vacuoles were observed in the cytoplasm. With the sublethal dose an increase in the amount of small and large cytoplasmic lipid droplets occurred. These ultrastructural changes parallel the pathological events which lead to animal death by hemorrhagic shock. PMID- 3109076 TI - Effect of cord factor, a toxic glycolipid from Mycobacterium tuberculosis, on mouse liver drug metabolizing enzymes. AB - Cord factor (a mycobacterial toxin) treatment of mice for 72 hr resulted in decreased activities of hepatic drug metabolizing enzymes. The toxin treated animals exhibited reduced levels of liver cytochrome P-450 and cytochrome b5, accompanied by significant lowering of NADPH-cytochrome c reductase and NADH cytochrome b5 reductase activities. The hepatic activities of aminopyrine N demethylase and aniline hydroxylase were diminished, while liver cytosolic glutathione S-transferase activity was inhibited in mice receiving the toxin. Earlier studies from this laboratory (J. K. Batra, Ph.D. Thesis, Delhi University, India, 1982) on the effects of experimental tuberculosis on hepatic drug metabolism revealed changes similar to the presently reported influence of cord factor on mouse liver microsomal monooxygenases. Thus, the action of cord factor (on hepatic drug metabolism) largely mimics the effects of tuberculosis infection. PMID- 3109077 TI - The influence of aging on intestinal absorption of TCDD in rats. AB - The effects of age on intestinal absorption of 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) were studied using adult male Fischer-344 rats of 3 different age groups: 13 weeks old (young), 13 months old (mature), and 26 months old (senescent). Absorption was measured with an in situ intestinal recirculation perfusion procedure. Absorption expressed in terms of ng TCDD absorbed/g intestinal dry weight/h was 166, 149 and 143 ng/g/h in the young, mature and senescent groups, respectively. When absorption was calculated in terms of ng TCDD absorbed/g mucosal dry weight/h, the decrease between the senescent rats and the 2 younger age groups, from 544 ng/g/h (young) to 351 ng/g/h (senescent), was not statistically significant (P less than 0.05). It was demonstrated that absorption of TCDD was unaffected by the presence of 2,4,5,2',4',5' hexachlorobiphenyl (HCB) in the perfusate, but that HCB absorption was (P less than 0.01) enhanced by the presence of TCDD. PMID- 3109078 TI - Hyperglycemia reduces the extent of cerebral infarction in rats. AB - Although hyperglycemia is known to exacerbate neuronal injury in the setting of reversible brain ischemia, its effect on irreversible thrombotic infarction is less well understood. In this study, unilateral thrombotic infarction was induced photochemically in the parietal cortex of Wistar rats. Seven days later, brains were perfusion-fixed for light microscopy. Infarct areas were measured by computer-assisted planimetry on multiple coronal sections at 250-micron intervals; these data were integrated to yield infarct volumes. Fasted, normoglycemic rats were compared with hyperglycemic rats that had received 1.2 1.5 ml of 50% dextrose i.p. 15 minutes prior to the induction of infarction. Infarct volume averaged 12.5 +/- 4.0 mm3 (mean +/- SD) in rats (n = 14) with plasma glucose levels of 72-184 mg/dl; this differed statistically from the average volume of 9.3 +/- 3.3 mm3 observed in rats (n = 13) with elevated plasma glucose (range 264-607 mg/dl). Spearman rank correlation analysis confirmed a significant correlation of larger infarct volumes with lower plasma glucose levels. In contrast, rats receiving mannitol i.p. to produce an osmotic load comparable with that of the dextrose-pretreated animals showed larger infarct volumes than saline-treated controls. The small but definite beneficial effect of hyperglycemia in this end-arteriolar thrombotic infarction model is possibly attributable to improved local energy metabolism at the periphery of the lesion during the early period of lesion expansion. PMID- 3109079 TI - Cerebral effects of extended hyperventilation in unanesthetized goats. AB - Thirty-six adult, male unanesthetized goats were hyperventilated to a PaCO2 level of 16-18 mm Hg for 6 hours. Arterial and sagittal sinus blood and cerebrospinal fluid were analyzed for pH, blood gases, bicarbonate, lactate, and pyruvate before hyperventilation, during hyperventilation, and after the termination of hyperventilation. Total cerebral blood flow, regional brain blood flows, and cerebral metabolic rate for oxygen were calculated from the distribution of radioactive microspheres. Intracranial pressure was measured in either the right or left cerebral ventricle. With the initiation of hyperventilation, cerebral blood flow and cerebral metabolic rate for oxygen fell significantly (64 +/- 5 ml/100 g/min to 41 +/- 3; 4.6 +/- 0.3 ml O2/100 g/min to 3.6 +/- 0.2), but both returned to prehyperventilation values within 6 hours of hyperventilation. With termination of hyperventilation, cerebral blood flow and cerebral metabolic rate for oxygen increased significantly above control levels (64 +/- 5 vs. 105 +/- 9; 4.6 +/- 0.3 vs. 5.4 +/- 0.4). Intracranial pressure was unaffected by hyperventilation or its termination. Arterial and sagittal sinus blood and cerebrospinal fluid pH increased with hyperventilation but returned to control values by 6 hours. However, pH was still significantly elevated at 6 hours. Lactate and pyruvate followed a similar pattern except in the cerebrospinal fluid, where both increased throughout the course of hyperventilation. There were no significant differences in the lactate:pyruvate ratio. On termination of hyperventilation, pH of the arterial and sagittal sinus blood and cerebrospinal fluid fell below control levels. Bicarbonate values decreased in all fluid compartments and were still below control values 2 hours after the cessation of hyperventilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109081 TI - [A new measurement device for the control of a halogen light polymerization lamp]. PMID- 3109080 TI - Graded neurologic scale for use in acute hemispheric stroke treatment protocols. AB - A standardized neurologic assessment scoring instrument was developed and tested for use in a multicenter trial of hypervolemic hemodilution in acute hemispheric stroke. Components of the neurologic examination pertinent to hemispheric stroke syndromes were emphasized. The scale was evaluated using 16 acute stroke patients for concurrent validity (Pearson coefficient r = 0.89 compared with global assessments by neurologists or neurosurgeons) and interobserver reliability (r = 0.95 interobserver reliability estimate). Such a scale should prove useful in quantifying neurologic deficits in hemispheric stroke and in following changes in neurologic status during multicenter acute treatment protocols. PMID- 3109082 TI - Analysis of human prenatal and postnatal thymocytes with the anti-Tac monoclonal antibody and recombinant interleukin-2. AB - The expression of the interleukin-2 (Il-2) receptor on the cell surface membrane of human prenatal and postnatal thymocytes has been studied by flow cytometry. The in vitro responsiveness of these thymocytes to human recombinant Il-2 (rIl-2) was also studied. Prenatal and postnatal thymocytes contained very few Tac positive cells. The different T cell antigens T6, T3, T4, T8, T9, T10, 3A1 and T11 were expressed by the first trimester of fetal development. Recombinant Il-2 alone was able to induce proliferation of human prenatal and postnatal thymocytes. From this study and data in the literature we conclude that hither-to a thymic precursor cell carrying the interleukin-2 receptor as is the case for the murine thymus has not been found in man. PMID- 3109083 TI - T-lymphocyte subsets in nude mice with Giardia muris infection. AB - The aim of this study was to compare the relative percentages of T-lymphocyte subsets in athymic (nude) mice and immunocompetent BALB/c mice, with and without Giardia muris infection. Suspension of mononuclear leukocytes from blood, spleen, and Peyer's patches of uninfected mice were incubated with fluorescent monoclonal antibodies (MAbs) directed against mouse T-lymphocytes (anti-Thy-1.2 MAb), T helper/inducer lymphocytes (anti-L3T4 MAb), or T suppressor/cytotoxic lymphocytes (anti-Ly-2 MAb), and examined by fluorescence microscopy to quantify each of these cell populations. While the percentages of Thy-1.2+, L3T4+, and Ly-2+ lymphocytes are all reduced in nude mice, L3T4+ lymphocytes were found to be especially depleted, resulting in a reversed L3T4+/Ly-2+ ratio (less than 1) in all of the nude mouse tissues examined. BALB/c and nude mouse Peyer's patch T cell subsets were quantified at various times during enteric Giardia muris infection. Unlike immunocompetent BALB/c mice, nude mice have an impaired ability to clear this infection. It was found that clearance of G. muris infection is associated with a Peyer's patch L3T4+/Ly-2+ ratio of greater than or equal to 2, and that this infection does not alter the percentages of Peyer's patch Thy-1.2+, L3T4+, or Ly-2+ lymphocytes in BALB/c mice or nude mice. The data obtained in the present work and in other studies suggest that the impaired capacity of nude mice to clear G. muris infection results from deficiency of L3T4+ lymphocytes. PMID- 3109084 TI - The efficacy of intensive plasma exchange in acquired von Willebrand's disease. AB - This study describes the response to therapeutic plasma exchange in a 60-year-old man with Waldenstrom's macroglobulinemia who developed a clinically severe bleeding disorder with laboratory features characteristic of acquired von Willebrand's disease. The patient's plasma levels of factor VIII coagulant activity, von Willebrand's factor antigen, and ristocetin cofactor activity were all less than 15 percent of normal, and the bleeding time was more than 20 minutes. In vitro studies did not demonstrate an inhibitor to factor VIII/von Willebrand factor, nor was a precipitating antibody to von Willebrand's factor antigen found in the patient's plasma. Neither infusions of cryoprecipitate nor combination chemotherapy corrected the clinical or laboratory abnormalities. In contrast, plasma exchange corrected the in vitro coagulation abnormalities and was effective in preventing surgical hemorrhage and controlling severe mucosal bleeding on 11 separate occasions. The current case demonstrates that the clinical and laboratory abnormalities in a patient with acquired von Willebrand's disease can be corrected completely by plasma exchange; it is recommended therefore that plasma exchange be considered as a mode of therapy in symptomatic patients with this disorder. PMID- 3109085 TI - Limitations of paternity testing calculations. AB - A total of 252 black and white trios (mother, child, and putative father) in which the alleged father was known not to be the biological father (BF) were generated from paternity studies. The likelihood of paternity (W) and the paternity index (P) were calculated on the basis of ABO, Rh, MNS, and HLA phenotyping. The results were then reviewed to evaluate the arbitrary limits proposed by a number of states in recent paternity legislation. Two hundred forty four of 252 non-fathers (NFs) (96.8%) were excluded. Of the 152 white NFs, 147 (96.7%) were excluded; 97 of the 100 blacks (97%) were excluded. Eight NFs could not be excluded by the routinely performed tests. The W value for those eight trios ranged from 1.2 to 98.8 percent. Based on limits proposed in legislation, had the NFs actually been alleged fathers, as many as four of the eight of these men could have had the burden of proving that they were not the BFs. PMID- 3109087 TI - Bovine serum albumin density gradient isolation of rat pancreatic islets. AB - The use of a bovine serum albumin (BSA) density gradient for isolation of rat pancreatic Islets of Langerhans after collagenase digestion has been compared with the standard Ficoll separation technique. The criteria studied were islet yield (insulin extraction of the islet interfaces and pellet), purity of preparation (amylase content of the islet preparation), insulin release characteristics, and the result of isologous transplantation in diabetic rats. The islet interface of the BSA gradient contained 62.2% of the total insulin, whereas the corresponding interface of the Ficoll gradient contained only 36.6% (P less than 0.001). The amylase content of the Ficoll-separated islet preparation was 6133 U/L, as opposed to 1230 U/L with BSA (P less than 0.001). BSA-isolated islets gave similar insulin release characteristics to non-density gradient-isolated islets, whereas Ficoll-separated islets showed suboptimal insulin release. Single-donor-single-recipient transplantation was successfully performed with BSA-isolated islets whereas multiple donors were required with Ficoll-separated islets. Thus significantly improved results were found with the bovine serum albumin density gradient separation in all criteria and consequently the use of this gradient represents an advance in islet isolation techniques. PMID- 3109086 TI - Liver preservation for transplant. Evaluation of hepatic energy metabolism by 31P NMR. AB - 31P NMR spectroscopy proved to be an excellent, dynamic, nondestructive method for assessing the liver during cold flush and pulsatile perfusion experiments. 31P NMR spectroscopy was used to measure ATP decay, inorganic phosphate appearance, and phosphate chemical shift in the excised mouse livers subjected to cold and warm ischemia. Cold flush followed by cold preservation in saline, Krebs Henseleit buffer, or Collins' solution showed that Collins' solution resulted in the slowest ATP decay. In temperature-controlled experiments (5 degrees -37 degrees C), ATP decay was much slower with lower temperature. In separate pulsatile perfusion experiments with oxygenated Krebs-Henseleit buffer, hepatic ATP was unchanged for at least 6 hr at 20 degrees C. At 37 degrees C, the NMR spectrum showed changes in the diphosphoesters region, but the ATP remained stable during the 6-hr perfusion. These studies suggest that for long periods of liver preservation, an adequate perfusion method should be developed. PMID- 3109088 TI - Positive effect of prophylactic total parenteral nutrition on long-term outcome of bone marrow transplantation. AB - In a randomized trial we studied the impact of providing total parenteral nutrition (TPN) to bone marrow transplant (BMT) patients during their cytoreductive therapy, and for 4 weeks following BMT, on 8 parameters of outcome. A total of 137 patients over 1 year of age and with normal nutritional status were randomized either to receive TPN starting one week prior to transplant or to receive hydration with a 5% dextrose solution containing electrolytes, minerals, trace elements, and vitamins. TPN was ultimately required by 40 of the 66 control patients when nutritional depletion was documented. Average total calorie and protein intake was significantly higher for the TPN group than for the control group. Minimum follow-up was 1 year and median was 2 years. Overall survival, time to relapse, and disease-free survival were significantly improved in the TPN group. Engraftment, duration of hospitalization, and incidences of acute and chronic graft-vs.-host disease and bacteremia were not different. Thus TPN during BMT had a positive effect on long-term outcome. Prophylactic nutritional therapy appears to be indicated even for well-nourished individuals during cytoreduction and BMT. PMID- 3109090 TI - Lobar pneumonia and pneumatocele formation due to Salmonella paratyphi B in an infant. PMID- 3109089 TI - Valproate for epilepsy in renal transplant recipients receiving cyclosporine. PMID- 3109091 TI - [Morquio-Brailsford disease in a refugee from Vietnam. Orthopedic and social arrangements]. PMID- 3109092 TI - The effect of pulsed ultrasound on the survival of Drosophila. AB - There are reports in the literature that the temporal peak intensity of pulsed ultrasound may be a better predictor of biological damage than is average intensity. The effects of temporal peak intensity on the survival of Drosophila melanogaster pupae exposed to pulsed ultrasound were investigated. Pulse average intensity and pulse repetition frequency were varied, while temporal average intensity and exposure duration were held constant. Thus, the total energy delivered was held constant. Survival was found to be directly dependent on pulse average intensity. We observed decreased survival at spatial average pulse average intensities as low as 0.5 W/cm2. PMID- 3109093 TI - Energy sources for intravenous nutrition. AB - Controversy exists concerning the appropriate use of carbohydrate solutions and fat emulsions as energy sources in intravenous nutritional regimens. Current evidence suggests that glucose is the carbohydrate energy source of choice and that when infused with appropriate quantities of protein it provides cheap and effective nutritional support in the majority of patients and clinical circumstances. During glucose infusion, blood glucose and acid-base balance should be closely monitored and, when indicated, exogenous insulin should be added to the regimen to combat hyperglycaemia and improve protein anabolism. Fat emulsions, although expensive, may justifiably be used in patients with moderate or severe stress to provide up to 50% of non-protein energy, especially in circumstances where attempts to satisfy energy requirements exclusively with glucose would impose an additional metabolic stress. PMID- 3109094 TI - Electron microscopic investigations of the cyclophosphamide-induced lesions of the urinary bladder of the rat and their prevention by mesna. AB - Fully developed cyclophosphamide-induced cystitis is characterized by nearly complete detachment of the urothelium, severe submucosal edema owing to damage to the microvascular bed and focal muscle necroses. The initial response to the primary attack by the cyclophosphamide metabolites seems to be fragmentation of the luminal membrane. This damages the cellular barrier against the hypertonic urine. Subsequent breaks in the lateral cell membranes of the superficial cells and in all the plasma membranes of the intermediate and basal cells, intercellular and intracellular edema and disintegration of the desmosomes and hemidesmosomes lead to progressive degeneration and detachment of the epithelial cells with exposure and splitting of the basal membrane. The morphological changes of the endothelial cells, which become more pronounced in the later stages of the experiment, the involvement of blood vessels regardless of their diameter and the location-dependent extent of the damage indicate a direct type of damage which is preceded by a mediator-induced increase in permeability, the morphological correlate of which is the formation of gaps in the interendothelial cell connections on the venules. These changes can be effectively prevented by mesna. The only sign of a possible involvement is the increase in the number of specific granules with a presumed lysosomal function in the superficial cells. PMID- 3109095 TI - Experimental determination of the kinetics of calcium-binding with chondroitin sulphate and the effects of uric acid on this process. AB - The calcium-binding kinetics of chondroitin sulphate C (CS) have been determined using equilibrium analysis including 45Ca. There is a linear relationship between the extent of the Ca binding and the concentration of CS present. 1 mumol CS disaccharide unit binds 0.757 mumol Ca. Scatchard plots of the data have revealed a single constant of dissociation (KD = 0.1429). In the presence of urate ions, and dependent on the pH value, the ability of CS to bind Ca may be impaired by as much as 31%. These measurements have supported the theory that urate ions interact with the GAGs in urine. PMID- 3109096 TI - [Kidney function parameters following ischemia stress using the Euro-Collins solution or the Bretschneider cardioplegic HTK solution]. AB - Protection-methods, for an improvement of ischemic tolerance of the kidney, can be investigated by intraischemic analysis of metabolism and structure. A definite proof for the effectiveness of a protection method is only postischemic function in combination with postischemic structure-regeneration. For this reason postischemic function was chosen for examination of the protective ability of the Euro-Collins-solution and the HTK-solution during a two-hour reperfusion period. We perfused 57 dog kidneys either with the Euro-Collins- or with the HTK-solution prior to ischemia. Ischemia was 7, 60, 90 and 120 min after Euro-Collins perfusion and 7, 120, 150 and 180 min after HTK-protection. The protected and ischemic kidneys were left in-situ; the mean ischemic temperature was therefore 20-25 degrees C for the shorter ischemic times and 30-34 degrees C for the longer ischemic times. We compared the protected and ischemic kidneys with 14 untreated kidneys (control). Postischemic renal blood flow (RBF) was measured by an electromagnetic flow probe; renal oxygen consumption (V02/min) was calculated by arterio-venous oxygen content difference and the renal blood flow. If urine could be collected, the glomerular filtration rate (GFR) was measured by an endogenous creatinine clearance. In Euro-Collins-protected kidneys after 60-120 min ischemia the RBF was after 15 min of reperfusion between 20 and 100 ml/min/100 g. After 30 min we got values of 100-200 ml/min/100 g. The V02/min, which was in the control kidneys between 5-6 ml/min/100 g, was about 2 ml/min/100 g.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109097 TI - Necrobiotic xanthogranuloma with paraproteinemia: case report and a pathogenetic theory. PMID- 3109099 TI - [Ossifying cyst of the maxillary sinus]. PMID- 3109098 TI - Examination of the retinal nerve fiber layer in the recognition of early glaucoma damage. PMID- 3109100 TI - [Congenital ureteral stenosis in paraureteral diverticulum of the bladder in children]. PMID- 3109101 TI - [Congenital anomalies simulating tumors and cysts of the abdominal cavity]. PMID- 3109102 TI - [Endogenous urea in the intestinal tract and its significance in nitrogen metabolism in ruminants]. AB - In the first series of experiments we studied in wethers the percent involvement of various parts of the intestinal tract (from duodenum to cecum) in the secretion of endogenous urea. We found out the following involvement of the given intestinal parts secreting urea to duodenum during 24 hours: bile 6.33%, pancreatic juice 1.85%, through the wall of the front part of jejunum 55.71%, through the wall of the rear part of jejunum 32.25% and through the cecum wall 3.86% of nitrogen of endogenous urea. The urea secreted to the mentioned parts represents one third of the total amount of endogenous urea transported to the entire gastrointestinal tract. Possibilities of utilizing this endogenous source of nitrogen in the organism of ruminant animals were studied in further experiments where 15N-labelled urea was applied to the cecum. We found out that more than four fifths of endogenous urea secreted to the small intestines returned to the metabolic circulation and that only less than one fifth was excreted, not being utilized anew in the organism. PMID- 3109103 TI - [Renal retention of urea in sheep]. AB - The urea-retaining ability of kidneys of ruminants and returning it back to the blood circulation are important features of the mechanism of nitrogen conservation in the organism. Applying the model of a low-nitrogen diet to sheep we found out the low fractional excretion of urea (FE urea) as a result of increased urea transport capacity in renal tubules. The decrease in the amount of excreted urea by 85% was also accompanied by a reduced glomerular filtration rate (GFR). We tried to verify our hypothesis by the cross-perfusion method that the renal excretion of urea in sheep is regulated by a factor circulating in the blood. We found out that FE urea decreased significantly in the cross-perfused kidney (in sheep on a high-nitrogen diet, connected to sheep on a low-nitrogen diet), without any changes in GFR. Our hypothesis is well-supported by the above result. The kidneys of sheep on low nitrogen diet retain urea through a decrease in the GFR and increased tubular urea transport. PMID- 3109104 TI - [Regulation of milk intake in young ruminants]. AB - We studied the influence of the three main nutritive components of milk - saccharides, fat and amino acids - on milk intake in suckling lambs and on the role of insulin as a key metabolic hormone for the regulation of milk intake. The intake was slowed down after p.o. administration of milk fat (p less than 0.05), after i. v. administration of methionine (p less than 0.001) and after p. o. administration of glucose, lactose (p less than 0.01, p less than 0.001) and sorbitol (p less than 0.001). After i. v. administration of glycerol, lysine, threonine, arginine, glucose, and i. v. and p. o. administration of galactose the intake of milk did not change significantly (p greater than 0.05). The findings indicate that the short-time regulation of milk intake in suckling ruminant animals is not subjected to the specific effect of some of the milk components. Regarding the metabolic effects, the problem concerns the speed of resorption of easily metabolizable sources of energy from the digestive system to the liver and to the whole body. Neutral Zn-insulin administered intraperitoneally at a dose of 4 U X kg-1 increased the milk intake (p less than 0.01, p less than 0.001), in 8 to 22 hours after the administration only when the animals were on the low-fat milk diet (5.9%-11% fat in dry matter). We assume that the long-range hyperphagy can be related mainly with the fast metabolizing of energy-rich substances (glucose) into the body stores (glycogen, fat) accompanied by subsequent hormonal changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109105 TI - [The effect of dietary lysine excess and deficiency on metabolism in Japanese quail]. AB - We conducted three experiments with Japanese quail to study the influence of deficient and excessive contents of lysine in the feed in relation to certain zootechnical parameters, protein value, to the active of liver xanthine dehydrogenase, content of free plasma lysine under the conditions of the maximum saturation of blood pool, and to the changes in 14C-labelled lysine degradation. The zootechnical parameters and protein value were optimum at the content of 5.22 g Lys per 16 g nitrogen in the feed, the activity of liver xanthine dehydrogenase was maximum. In a separate experiment the maximum saturation of blood pool determined with respect to a lysine supply in the feed reached the highest value at 6.88 g Lys per 16 g nitrogen and it decreased later on although the lysine supply increased. We assume the existence of a regulating mechanism that does not allow exceeding certain lysine concentrations in the blood plasma. Lysine degradation measured by the value of 14CO2 expired from 14C-labelled lysine was higher both with lysine deficient and excessive content, than with the lysine content in the feed approaching the required value. PMID- 3109106 TI - [Growth in broiler chickens after the regulation of sex differentiation using tamoxifen]. AB - We studied the influence of an embryonal application of antiestrogen tamoxifen on gonad differentiation and sex dimorphism during the growth of Slovgal chickens. A single application of 500 micrograms tamoxifen to the incubated eggs before the onset of gonad differentiation induced in pullets the growth of the right gonad, which usually develops only in cockerels. Comparing the size of both gonads it is clear that the above dose of antiestrogen had the 22.31% masculinizing effect. Morphological changes observed just after hatching correlated with the testosterone concentration in plasma. The pullets masculinized by tamoxifen had a significantly higher level of male hormone. The changes in sex differentiation were reflected in the altered growth of pullet bodies. With respect to the higher growth rate and more effective feed conversion, their growth can be appreciated as masculinized. The higher body weight at the end of seven-week fattening (4.25% in comparison with the control group of pullets) was due to the higher trunk weight. The growth was stimulated by tamoxifen application also in cockerels (5.57% increase in body weight) but it was not accompanied by any changes in feed conversion. PMID- 3109107 TI - An enzyme-linked immunosorbent assay for the serodiagnosis of turkey rhinotracheitis infection. PMID- 3109108 TI - Antibodies to TRT in chickens with swollen head syndrome. PMID- 3109110 TI - Experimental infection with Sarcocystis medusiformis in sheep. AB - The development of the parasite was studied in 48 sheep killed between 188 and 1132 days after experimental inoculation with Sarcocystis medusiformis sporocysts from cats. Immature sarcocysts were present at 188 days post inoculation (d.p.i.). At 331 d.p.i. macroscopic sarcocysts with an elongate fusiform appearance were seen in the laryngeal, abdominal and diaphragm musculature. The largest cyst measured 2 mm in length by 0.5 mm in width at 331 d.p.i.; histologically they contained metrocytes at the periphery of the cyst with more densely staining merozoites in the central region. By 443 d.p.i. typical 'thin' cysts 2-3.5 mm in length were seen in the flank and external thoracic muscles. By 765 d.p.i. sarcocysts were 5 mm in length. The ultrastructure of the cyst wall of these cysts resembled that of S. medusiformis. At 1132 d.p.i. sarcocysts measured 4 mm X 0.5 mm. PMID- 3109109 TI - The structure and identity of macroscopically visible Sarcocystis cysts in cattle. AB - Macroscopically visible Sarcocystis spp. cysts isolated from the skeletal muscle of slaughtered cattle were examined by light- and electronmicroscopy. Transmission experiments involving cats, dogs and a human volunteer were also carried out. The cysts could only be transmitted to cats which establishes them with a high degree of certainty as Sarcocystis hirsuta. The cyst wall (including protrusions) ranged from 3.3 to 7.0 micron in thickness and the individual cyst wall protrusions from 1.2 to 2.6 micron in width. Transmission and scanning electronmicroscopy revealed previously undescribed features of the cyst wall. It appears that, with increasing age, the cyst wall protrusions become larger and develop a highly irregular surface. Their attachments to the cyst wall are slender and widely spaced indicating that growth of the cyst continues without the formation of new protrusions. Within the protrusions the fibrils become disorganised and numerous osmiophilic granules appear. It is evident that major changes in the structure of sarcocysts can occur with age. PMID- 3109111 TI - Serodiagnosis of Fasciola gigantica infection in buffaloes. AB - The agar gel precipitation test (AGPT), counter immunoelectrophoresis (CIEP) and indirect haemagglutination (IHA) were evaluated for the diagnosis of fascioliasis due to Fasciola gigantica in buffaloes. The sensitivity of these tests varied with the intensity of infection; and was greatest when the fluke burden in liver exceeded 100. CIEP detected 76.06% of infected sera and was most sensitive, followed by IHA which detected 68.37% of the infected sera. The AGPT was found to be least sensitive, detecting only 57.4% of the infected sera. Although these tests were limited by the occurrence of false-positive reactions, their use may be an aid for effective diagnosis of fascioliasis in buffaloes. PMID- 3109112 TI - Establishment and initial characterization of continuous in vitro cultures of bovine T lymphocytes. AB - Utilizing human recombinant interleukin 2 (HrIL-2) in combination with several mitogens, continuously growing cultures of bovine lymphocytes have been established. Continuous presence of HrIL-2 is required to maintain the growth of these cultures but a requirement for continued presence of mitogen seems variable. Cloned lines have been derived from these cultures by limiting dilution and outgrowth in the presence of mitomycin C treated bulk cells. Cell surface phenotype analysis indicates that all of these cultures and cloned lines are of the T cell lineage. Functional analysis indicated that some of these cultured cells are cytolytically active in lectin mediated assays whereas others are not. Utilization of this technology for the growth and characterization of bovine T cells will undoubtedly contribute to an enhanced understanding of the bovine immune response mechanisms. PMID- 3109113 TI - Development of optimal conditions for lymphokine production by chicken lymphocytes. AB - Chicken thymus, spleen, and bursa lymphocytes were isolated by different methods and incubated under differing conditions in order to obtain and characterize avian lymphokines. The biological activity of lymphokine-containing cell culture supernatants was measured by their antiviral activity (interferon(IFN)-units) and by their capacity to induce cytostatic effects in bone-marrow-derived macrophages (50% cytostasis-inducing dose, CID). Lymphokine production by thymus lymphocytes required concanavalin A (ConA)-stimulation, while spleen cells, when cultured at high density, released CID and IFN activities into the culture medium even without mitogen-stimulation. By way of comparison, the highest lymphokine content was found in the supernatant of lymphocyte cultures, which were incubated for 72 hours at 41 degrees C after stimulation with an optimal ConA dose. For stimulation of thymus lymphocytes 30 micrograms ConA/ml were found to be optimal, independent of serum content and cell density in the cultures. In contrast, the optimal ConA dose for spleen lymphocytes not only depended on the serum content but also on the cell density in the cultures and varied within a range of 2.5 micrograms and 45 micrograms ConA/ml. PMID- 3109114 TI - Neutrophil phagocytic and serum opsonic response of the foal to Corynebacterium equi. AB - This study was undertaken to examine the neutrophil response to Corynebacterium (Rhodococcus) equi, and to assess the possibility of neutrophil immaturity or malfunction in predisposition to C. equi pneumonia in foals. Neutrophil phagocytosis of Corynebacterium (Rhodococcus) equi was studied in foals from birth to 6 months of age. Chemiluminescence (CL) and bactericidal assays were used to assay the phagocytic response of peripheral blood neutrophils to C. equi in vitro. Results of in vitro bactericidal and CL assays indicate that foal neutrophils are able to ingest and kill C. equi, however are significantly more efficient in the presence of opsonization with specific antibody, and less importantly complement. Neutrophil CL was significantly decreased (p greater than .05) or eliminated by antibody adsorption, heat-inactivation, or removal of serum from the assay. The ability of the neutrophil to kill C. equi, as measured by in vitro bactericidal assay, was greater than 90% killing by 6 hours, in the presence of C. equi antiserum. Bactericidal activity was reduced to less than 40% killing when C. equi adsorbed serum was used as the opsonin source. As CL results indicated complement involvement in the opsonization of C. equi, the temporal development of hemolytic and conglutinating complement was measured in normal and C. equi infected foals. Neither defects nor age-related suppression of neutrophil function or complement activity were detected in C. equi affected foals, suggesting that these are not pathogenic mechanisms involved in foal pneumonia. PMID- 3109115 TI - Host resistance and faecal sporocyst excretion in dogs exposed to repeated infection with Sarcocystis levinei. AB - A marked reduction in the faecal excretion of sporocysts was observed in experimental pups, following the repeated oral administration to them of buffalo cardiac muscle infected with Sarcocystis levinei. Sporocysts excreted from days 9 to 25 post-infection (pi) exhibited a gradual reduction in the quantum. Maximum intensity of excretion of sporocysts was recorded between days 9 and 16 pi, becoming moderate after day 16, light after day 21 and completely absent after day 36. After the subsequent feeding to pups of S. levinei infected buffalo cardiac tissues at 40 day intervals the quantity of sporocysts shed was less, the prepatent period was prolonged and the patent period was considerably shortened. The peak period of excretion varied depending upon the number of exposures of the pups to the infected S. levinei tissues from buffaloes (Bubalus bubalis). PMID- 3109116 TI - Design alternatives for integrating the National Medical Expenditure Survey with the National Health Interview Survey. PMID- 3109117 TI - [Nitrates in the treatment of hypoxic pulmonary hypertension]. PMID- 3109119 TI - [Effect of zinc on the body in protein-calorie malnutrition]. AB - It is shown that addition of zinc into the ration of pigs suffering from protein calorie deficiency leads to increased food consumption and its utilization in the body attended by a rise of the protein and fat absorption coefficient and by diminution of food expenditure for body mass increment. Immune processes are intensified which is expressed in the growth of the leucocyte count, phagocytic coefficient and blood neutrophil index. The nutrition improvement is manifested by the increase of body mass increment, red blood cell number and hemoglobin level in the blood, and by the shift of the leucocytic formula to the left; skin lesions disappear. In most animals these effects of zinc are manifest no less than the effect of protein addition to the ration. The most pronounced effect is obtained when zinc and protein are used simultaneously. PMID- 3109118 TI - [Ways of improving the diet therapy of industrial workers]. AB - A conceptual model of the organizational system of the diet therapy of workers at industrial enterprises has been developed. The system analysis permitted the authors to reveal its ineffective components and to outline the ways for their correction. Approbation of the system at industrial enterprises contributed to the improvement of the social-medical and social-economic effectiveness of the diet therapy under industrial conditions. PMID- 3109120 TI - [Experimental basis of principles for creating microbiologic standards for food products for children during the 1st year of life]. AB - Standard media were designed simulating the gastro-intestinal contents of infants during the first year of life. These media were used in the in vitro tests to study the viability of a number of potentially-pathogenic microorganisms. It was shown that S. aureus, E. coli O-III, S. liquefaciens not only survived but also multiplied in the media with pH values similar to those of gastric juice in infants of the first year of life, in the presence of the mixture for child nutrition "Malysh". The results obtained necessitate strict requirements for the absence of potentially-pathogenic microorganisms in definite volumes of dry milk mixtures and their components intended for child nutrition. PMID- 3109121 TI - [Evaluation of the effect of enriching rice protein with lysine and egg protein]. AB - The experimental biological value (BVe) of rice enriched with lysine and egg protein was studied in growing Wistar male rats with the use of new parameters for the evaluation of the new food protein quality: potential biological value (BVp) and compensation coefficient (C). Pure protein utilization and body weight of rats receiving the lysine-enriched diet were significantly higher than those in the animals given the rice ration. Similar values were recorded in the animals kept on the diet containing rice with egg protein. The new parameters (BVp and C) enable the evaluation of the food protein aminogram and estimation of the effect of rice enrichment with lysine and egg protein. PMID- 3109122 TI - [New findings concerning lysine as an essential amino acid]. PMID- 3109123 TI - [Role of Mycoplasma pneumoniae in meningitis and meningoencephalitis]. PMID- 3109124 TI - [Mechanisms of nitroglycerin action in experimental coronary insufficiency]. PMID- 3109125 TI - [Determination of the economic effectiveness of medical science and public health]. PMID- 3109126 TI - Donor notification for positive non-A, non-B hepatitis surrogate testing. PMID- 3109127 TI - [Waldenstrom's macroglobulinemia]. PMID- 3109129 TI - [Feeding of patients with acute pancreatitis]. PMID- 3109128 TI - [4 cases of a surgically treated central form of Recklinghausen's disease]. PMID- 3109130 TI - [Results following endoscopic paravasal long-term sclerosing of esophageal varices]. AB - Our experiences confirm that with endoscopical paravasal longterm sclerosing of esophageal varices the incidence of recidive bleeding can be clearly reduced and the probability of survival of the patients treated with this method can be improved. Recidive bleeding occurred in 38% of those patients treated with longterm sclerosing, in a conservatively treated group, on the other hand, in 61% of the cases. At the end of the observation period (January 1980 to December 1984) two thirds of the patients treated with sclerosing remained alive, in the control group, however, only one half of 71 patients survived. This favourable result can be attributed to reduced mortality because of bleeding, since the mortality of coma hepaticum and of other rare causes of death is nearly equal in both groups of patients. PMID- 3109131 TI - The biology of malaria parasites. Report of a WHO Scientific Group. PMID- 3109132 TI - Alternative systems of oral care delivery. Report of a WHO Expert Committee. PMID- 3109133 TI - The hypermetabolism organ failure complex. PMID- 3109136 TI - Gonorrhea: increasing in vitro resistance to antimicrobials; a 26-year perspective from the city of Milwaukee public health service. PMID- 3109135 TI - Cost-effective use of the surgical intensive care unit. PMID- 3109137 TI - [CO2 gas insufflation in headache]. PMID- 3109134 TI - Corticosteroids, nonsteroidal anti-inflammatory drugs, and naloxone in the sepsis syndrome. PMID- 3109138 TI - [The bolus problem]. PMID- 3109139 TI - [Physical therapy in degenerative diseases of the joints]. AB - By virtue of their wide spreading and their effects on the social working ability degenerative joint diseases increasingly gain significance. In the concept of therapy of this group of disease apart from pharmacotherapy and operative treatment physiotherapy plays an important role. After having proved that kinetotherapy is a form of treatment which is to be prescribed in the first place, the passive therapeutic methods such as thermotherapy (heat and cold), application of ultrasound, electrotherapeutic procedures, massages promising success in arthrosis are described and questions of dosage are discussed. At the same time the significance of a health resort therapy for this group of diseases in discussed. After a randomized analysis which includes 1,893 patients with arthrosis the ratio of active to passive forms of therapy during a course of treatment in the state health resorts Bad Brambach--Bad Elster in 44 to 56%. Finally it is referred to the particular tasks of the pre- and postoperative physiotherapy in the advanced stages of an arthrosis before and after implantation of artificial joint replacement. PMID- 3109140 TI - [Gastric acid, pepsin secretion and mucosal blood flow--their modification by the sympathetic nervous system]. AB - The effects of surgical and chemical sympathectomy on various gastric functions was studied in rats. From the results it is concluded that the sympatho-adrenal system inhibits gastric acid secretion and mucosal blood flow. The regulation of pepsin secretion by the sympathetic nervous system appears controversial: under normal conditions an inhibitory effect is prevailing, whereas under stress an increase in pepsin secretion is observed. PMID- 3109141 TI - [Long-term pH-metry and manometry: methods and value in the differential diagnosis of retrosternal pain]. PMID- 3109142 TI - [Clinical and hemodynamic effects of nisoldipine and captopril in heart failure: a double-blind comparative study of long and short-term effects]. AB - Afterload reduction with angiotensin-converting enzyme inhibitors (ACE inhibitors), such as captopril, is an established therapeutic measure in the adjunctive treatment of severe chronic heart failure. Unfortunately, several side effects and adverse reactions are related to this form of therapy. Calcium antagonists of the dihydropyridine group can also induce a similar afterload reduction, and substances of this group exhibit only a few adverse reactions. In the present double-blind study, the acute and chronic hemodynamic and clinical benefits of the calcium antagonist nisoldipine (= BAY K 5552) were compared with captopril in the adjunctive treatment of patients with heart failure (NYHA III or IV). The study group consisted of 17 patients. After randomization, 9 were treated with captopril (25 mg orally t.i.d.) and 8 with nisoldipine (3 were given 20 mg orally t.i.d., and 5 were given 20 mg b.i.d.). The following hemodynamic variables were obtained in the control phase after 3 days and 3 months' duration of treatment: heart rate, LVEF, SVI, ESVI, EDVI, PSP/ESVI (ratio of peak systolic pressure and end-systolic volume index), CI and systemic vascular resistance. The clinical status of the patients was assessed by means of seven criteria on an arbitrary scale. The following results were obtained: for the nisoldipine group, the average LVEF increased significantly from 0.26 to 0.31 within 3 days of treatment, but after 3 months, this increase had disappeared. All other hemodynamic parameters did not change significantly within either 3 days or 3 months of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109143 TI - Oligoclonal antibodies in CSF of patients with meningopolyneuritis Garin-Bujadoux Bannwarth: Ig class, light chain type and specificity. AB - Detection of intrathecally produced antibodies in cerebrospinal fluid (CSF) of patients with meningopolyneuritis Garin-Bujadoux-Bannwarth (MPN-GBB) is well documented. Analysis of CSF has revealed the oligoclonal nature of these antibodies. We investigated oligoclonal antibodies (OA) in CSF and serum of MPN GBB patients with regard to immunoglobulin class, light chain type and specificity and compared the findings with those in other neurological diseases (OND). For this purpose an immunofixation (IF) technique after agarosegel electrophoresis (AE) of concentrated CSF was used. 87% of patients with MPN-GBB demonstrated in the acute stage of their disease oligoclonal bands (OB) in their CSF which could not be detected in paired serum samples. IF revealed in most cases of MPN-GBB IgG banding. While IgM banding was a common finding in CSF of MPN-GBB patients, this was not the case in OND. Specificity of CSF OA against components of Borrelia burgdorferi could be demonstrated by agarose isoelectric focusing (AIEF), transfer to nitrocellulose paper and reaction with 125I labelled B. burgdorferi antigen. PMID- 3109146 TI - [Bacteriological, clinical, and pharmacokinetic studies of perioperative antibiotic prophylaxis in head and neck surgery]. AB - The point of this study was to analyze the possible benefits of perioperative antibiotic prophylaxis in patients from whom oral cavity or throat tumors are removed. The criteria used to judge the efficacy of each treatment included the clinical course of the treatment, the bacterial colonization of the surgical area as well as the growth of bacteria during the postoperative phase. 50 patients were chosen and grouped according to their surgical treatment: laryngectomy (n = 20), partial laryngectomy (n = 22) or tongue, floor of the mouth, soft palate, gum or base of the tongue partial resection (n = 8). Within each surgical group, patients were randomly chosen for antibiotic prophylaxis; others constituted the untreated control group. The antibiotic prophylaxis consisted of 5 g Mezlocillin administered at the time of narcosis for 20 min followed by 0.5 g Metronidazol for 10 min. These medications were given in 8-hour intervals for three days following surgery. Investigation of the first 20 patients (prophylaxis group n = 7, control group n = 13) revealed that the combination of Mezlocillin and Metronidazol positively influenced post-operative recovery (no complications) while the patients without prophylactic antibiotic treatment suffered general or local complication leading to, in 10 cases, the necessity of postoperative therapy. On the basis of these results, the random grouping of the patients was ended and all 30 remaining patients were given the antibiotic prophylaxis. Regardless of antibiotic treatment, the great majority of microbes isolated from throat swabs and tracheal secretions were gram-negative, aerobic bacteria. A prerequisite for efficacious prophylaxis is that the antibiotics be applied before the operation, so that a sufficient concentration is present at the time of pharyngotomy. On the basis of pharmacokinetic investigations, administration of the antibiotic 30 min preoperatively fulfills this requirement. Further, our recommendation, based on our measurement of the spectrum of bacteria present and their growth is that the antibiotics be applied over a period of three days postoperatively. This recommendation is also based on the fact that some patients (those having undergone partial laryngectomy or tongue, floor of the mouth, base of the tongue partial resections) have suffered loss of the swallowing reflex so that there exists a continuous contamination of the surgical area with pathogens or facultative pathogens coming from the nasal or oral cavities. PMID- 3109144 TI - Treatment of Lyme disease. AB - We compared phenoxymethyl penicillin, erythromycin, and tetracycline, in each instance 250 mg four times a day for 10 days, for the treatment of early Lyme disease (stage 1). None of 39 patients given tetracycline developed major late complications compared with 3 of 40 penicillin-treated patients and 4 of 29 given erythromycin (p = 0.07). However, with all three antibiotic agents, nearly half of patients had minor late symptoms. For neurologic abnormalities (stage 2), 12 patients were treated with high-dose intravenous penicillin, 20 million U a day for 10 days. Pain usually subsided during therapy, but a mean of 7 to 8 weeks was required for complete recovery of motor deficits. For the treatment of established arthritis (stage 3), 20 patients were assigned treatment with intramuscular benzathine penicillin (7.2 million U) and 20 patients received saline. Seven of the 20 penicillin-treated patients (35%) were apparently cured, but all 20 patients given placebo continued to have attacks of arthritis (P less than 0.02). Of 20 arthritis patients treated with intravenous penicillin G, 20 million U a day for 10 days, 11 (55%) were apparently cured. Thus, all 3 stages of Lyme disease can be treated with antibiotic therapy, but some patients with late disease may not respond. PMID- 3109148 TI - [A data processing system for bacteriological and chemical water analysis]. AB - Using the "Natural" computer language a menu-guided system for cataloguing, processing and evaluating bacteriological and chemical water analyses was designed. The program can be employed to different blocs of analyses, e.g. "TrinkwV"-analyses, standard-analyses, those on volatile chlorinated hydrocarbons and bacteriological water analyses as well. For each water sample the actual, the last and the next to the last value, also arithmetical means, minimal and maximal are stored and can be retrieved. The evaluation of the bacteriological analyses and those of the volatile chlorinated hydrocarbons is carried out by a choice of text variants, whereas the TVO- and standard-analyses are interpreted automatically. Managing laboratory data has become much easier during our three years experience using this system for information storage, search and retrieval in water research and routine; even untrained users are able to handle it after a short period of tuition. PMID- 3109147 TI - [Carcinogenic activity of ethylene oxide and its reaction products 2 chloroethanol, 2-bromoethanol, ethylene glycol and diethylene glycol. III. Research on ethylene glycol and diethylene glycol for carcinogenic effects]. AB - Ethylene glycol and diethylene glycol were each administered once weekly subcutaneously to groups of 100 female NMRI mice at 3 dosages (30; 10 und 3 mg single dose per mouse). Tricaprylin was used as solvent. The mean total dosage per mouse was 2110.5; 707.0 and 196.2 mg for ethylene glycol and 2029.8; 671.7 and 213.3 mg for diethylene glycol. Neither ethylene glycol nor diethylene glycol induced tumors at the injection site or away from the point of administration. PMID- 3109149 TI - [Mutagenic activity in the feces of normal people on a mixed diet]. AB - Single fecal samples of 25 people, living on a normal mixed Western diet and matched for freedom from any gastrointestinal disorder, were freeze-dried and volatile compounds were collected at -60 degrees C. The residues were extracted with n-hexane-dichloromethane 1:1, and subsequently with acetone-ethylacetate 2:1. The three fractions were assayed for mutagenic activity using the Salmonella typhimurium mammalian microsomal system. Fecal mutagenic activity was observed with the tester strain TA 98 in 28% of the assayed people without microsomal activation, and in 4% of the people with strains TA 98 and TA 100 with microsomal activation. PMID- 3109145 TI - Treatment and course of erythema chronicum migrans. AB - 72 patients with Erythema chronicum migrans were treated with phenoxymethyl penicillin, 1,5 mill. IU p.o. three times a day for 14 days. Two children got the same therapy, but in a dosage of 400,000 IU three times a day for 10 days. In three of 15 skin samples, taken from the periphery of ECM lesions, spirochetal organisms were isolated. Of the 72 patients 16 had raised IgG (greater than or equal to 128) and 9 had raised IgM (greater than or equal to 64) titers to Borrelia burgdorferi. Under treatment with phenoxymethyl penicillin (penicillin V) all ECM lesions resolved within 6 to 10 days. After an observation period of 9 to 14 months no major or minor late manifestations of Lyme disease have developed in any of the 72 patients. PMID- 3109150 TI - [Hygiene as a behavior problem]. AB - The subject of the study is a systematizing analysis of present research concerned with the barriers which prevent scientific findings about hygiene from being carried out and which hamper the obvious adoption of hygienically and psycho-hygienically relevant prophylactic measures. A general interpretive model with explanatory value for health- and hygiene-related behavior is being developed. Future studies will particularly have to clarify what significance and what interpretative relevance do the diverse influencing factors have for a particular person in a particular position and situation and how in the course of one's biography even something like lifestyles of hygienic behavior develop and change. For the necessity of improvement as regards the hygienic status in various realms of life the knowledge about existing barriers is a basic essential. The following quantities and constructs pass into the theoretic interpretive model which should also provide the basis for further evolvement of theories as well as the starting point for specific research hypotheses but not least for the development of specific research and evaluation designs: Standard of information, informational behavior and quality of information. The individual risk assessment: A function of the subjective importance and probability that benefit and cost factors of prophylactic behavior will occur. Additional influencing factors essential to the development of a desirable health- and hygiene-related behavior are: Objective shortcomings with regard to prophylaxis: deficits of the hygienic research including the deficits concerning the development of feasible and universally applicable disinfection methods. Hazards connected to prophylaxis: Objective risks with regard to prophylaxis (disinfection methods which may cause allergies, which involve problems with the compatibility of materials and so forth) and psychological risks (impaired relations between physician and patient due to the wearing of a mouth guard in dental practice, and others) are being differentiated. The degree importance attached to hygiene in organisations: prerequisites for this are: matters of hygiene as features characteristic of a specific job and as a part of employee evaluation, laying down of responsibilities and spheres of competence in matters of hygiene, normative binding character of job-related hygienic guidelines, exemplary behavior of the management.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3109151 TI - Abstracts of papers presented at the congress of the Deutsche Gesellschaft fur Hygiene und Mikrobiologie, Section Hygiene and Public Health. Bochum, 2-5 October 1985. PMID- 3109152 TI - [Carcinogenic industrial substances--a review of the present information]. AB - The potential carcinogenic risks of chemical substances at the workplace show increasing importance in occupational and environmental medicine, but the problems are also discussed controversially. Based on national and international literature estimations according the portions of occupational cancer are given. In accordance with former estimations from our institute, it is concluded, that 1 2% of all cancer deaths are caused by work and profession. A review of data from newer literature shows, that the numbers of chemicals with carcinogenic potency vary considerably. This is mainly due to the largely unknown mechanism of carcinogenesis, aspects of syncarcinogenesis and cocarcinogenesis as well as the different evaluation of mutagenicity-, short-term- and animal-tests on the one hand and of epidemiologic as well as casuistic studies on the other hands regarding carcinogenicity of chemicals for humans. In this context, the importance of epidemiologic studies for detecting unknown cancerogenic risks for humans is emphasized. In the field of occupational medicine it is relevant to differ between compensation and prevention. According to this aspects, for compensation of a malignant tumor as an occupational disease, more strict criterias must be fulfilled to objectify the carcinogenicity of a substance for humans than for preventive measures. On the basis of the monographs as well as reviews of the International Agency for Research on Cancer (IARC) the single substances, mixture of substances and industrial processes with proven or probably carcinogenicity for humans are given. In comparison to the monograph of Hueper from 1963 it is concluded, that until now no critical increase of carcinogenic substances at the workplace has occurred. For preventive efforts at the workplace, the medical examinations are important. These are based on various regulations by law or by German Employers Liability Insurance. In conclusion, recommendations and demands are given regarding prevention, evaluation and compensation of malignant diseases as well as detection of unknown carcinogenic risks for humans at the workplace. PMID- 3109153 TI - Microbiological evaluation of drinking water construction materials--comparison of two test procedures. AB - Materials used in contact with drinking water can impair water quality by supporting the growth of aquatic microorganisms. In order to prevent this problem several different test procedures have been developed but to date no comparative study of the performance of these methods has been published. During collaborative studies between the regional laboratories of the Thames Water Authority, London, and the Institute of Hygiene, University Bonn, duplicate samples of 11 PVC materials were exchanged and evaluated by the standard methods used in the United Kingdom (UK) and the Federal Republic of Germany (FRG). There was a good agreement between the results as assessed by the published criteria. When a stricter criterion for interpreting the results of the UK method was applied to the findings, a complete agreement between the methods was observed. PMID- 3109154 TI - Analysis of the microbiological particulates in municipal drinking-water by scanning electron microscopy/X-ray energy spectroscopy. AB - Scanning electron microscopy and X-ray energy spectroscopy (SEM/XES) were used to survey the biological and nonbiological particles in two different municipal drinking-water systems. Microbiological particles could be differentiated from non-biological by their qualitative elemental compositions and this information was used as the basis for an automated detection scheme. Automated SEM/XES analyses were used to demonstrate microbiological differences between well-water and surface-water in distribution systems. PMID- 3109155 TI - [Identification of health endangering substances in air pollution]. AB - In a health-related evaluation of the environment, timely recognition of possible health hazards is of much greater significance than describing health injuries that have already occurred. The following model has been found to be workable: The entire study consists of 4 parts which are quite significant when compared with each other and analyzed statistically. (1) Detailed interviews with physicians in practice in the area examined (2) Spirometric tests among school children in third and fourth grades (elementary school) (3) Questionnaires to be completed by the parents of the school children examined, in which the questions implied in (1) are also included. (4) The results obtained are compared to the available data pertaining to the air quality in the region. Possible exposure to adverse indoor conditions in schools and homes are also taken into consideration. PMID- 3109156 TI - Influence of biofilms by chemical disinfectants and mechanical cleaning. AB - Water conducting systems in hospitals (endoscopes, nebulizers, tap water systems, dental units etc.) are often important reservoirs of conditional pathogens. The sanitation of those systems by in vitro efficient chemical disinfectants is very difficult. An explanation may be that microorganisms are growing in such systems in wall adhering biofilms wherein they are protected from biocides. A method for testing the efficacy of chemical disinfectants and mechanical cleaning is described under conditions which imitate those in natural systems. A criterion for the efficacy of sanitation procedure is not only the good disinfection result but also the removal of biofilms. The investigation showed that aldehydes, and peracetic acid can reduce multiplying microorganisms without disrupting the biofilm. A preparation on the basis of hydrogen peroxide showed good antimicrobial efficacy and a distinct reduction and influence of the biofilm. The best result was achieved by mechanical cleaning. The test model is simple and a supplement to the conventional in vitro laboratory test for the efficacy of sanitation procedures of water conducting systems. PMID- 3109157 TI - Age-dependent oral bioavailability of erythromycin thiocyanate in calves. PMID- 3109158 TI - Hepatic capacity for ammonia removal in sheep. PMID- 3109159 TI - Dopamine and norepinephrine in the diencephalon of ovariectomized and sham operated hens around sexual maturity. PMID- 3109160 TI - In vitro studies on the lipogenetic ability of the hen oviduct. PMID- 3109161 TI - Cranial metastasis of canine transmissible venereal sarcoma. PMID- 3109162 TI - The effects of prolonged fasting on glucose tolerance and insulin response to intravenous glucose in normal dogs. PMID- 3109163 TI - Xylazine-induced vomiting in dogs: elimination by ablation of the area postrema and blockade by yohimbine. PMID- 3109165 TI - Uterine cannulation in the bitch. PMID- 3109164 TI - [Meiosis in cattle, sheep, goats and swine in late prophase and metaphase]. PMID- 3109166 TI - Bovine dwarfism: clinical, biochemical, radiological and pathological aspects. PMID- 3109167 TI - [Significance of glucocorticoids as a stress parameter in cattle during the peripartum period]. PMID- 3109168 TI - [Effects of a grain-rich feed mixture without trace element and vitamin supplement on different performance parameters of fattening pigs]. PMID- 3109169 TI - Comparative effects of selenium in oats, meat meal, selenomethionine and sodium selenite for prevention of exudative diathesis in chicks. PMID- 3109170 TI - Acetylation and hydroxylation of sulphatroxazole by the turtle Pseudemys scripta elegans. PMID- 3109171 TI - The influence of osmotic pressure, lactic acid and pH on ion and fluid absorption from the washed and temporarily isolated reticulo-rumen of sheep. PMID- 3109172 TI - Studies on glutamate dehydrogenase from rumen bacteria of buffalo (Bubalus bubalis) and cow. PMID- 3109173 TI - [Maturational changes in the ECG of cattle. I. Ventricular activation]. PMID- 3109174 TI - [Pathogenic characteristics of Pseudomonas aeruginosa]. AB - P. aeruginosa strains isolated from clinical material have been found capable of inducing various types of lesions in agricultural plants: tissue growth, soft and dry rot, changes in the color of plant tissue. In connection with the capacity of P. aeruginosa for adaptation to various conditions of existence, plants may be one of the reservoirs of infection. The authors suggest the P. aeruginosa is not an opportunistic, but a complete pathogen with a high degree of adaptability to the environment. PMID- 3109175 TI - Bile pigments inhibit microsomal lipid peroxidation. AB - Bile pigments (bilirubin and biliverdin) inhibit lipid peroxidation in rat liver microsomes at physiological concentrations. Since an alternative course for bilirubin degradation involving superoxide radical has been described, a possible explanation of the decrease of the initial rate of lipid peroxidation could be the scavenging of .O2-. PMID- 3109176 TI - Poly(ADP-ribose) and replicative DNA synthesis studied in permeable mouse thymocytes. AB - Poly(ADP-ribose) and DNA synthesis were followed in a random population of freshly isolated and permeabilized mouse thymocytes. Different conditions were found to be optimal for the synthesis of poly(ADP-ribose) and DNA, respectively. The suspension of one of the processes did not influence significantly the synthesis of the other macromolecule. Our results suggest that there is no direct relationship between the two processes. PMID- 3109177 TI - A novel method for the isolation of carboxypeptidase B. AB - Carboxypeptidase B was isolated from porcine pancreas by selective heat treatment of the autolyzed tissue at 60 degrees C and pH 6.0 the presence of phosphate ions. The heat treatment was followed by ammonium sulfate fractionation and ion exchange in a batch system. The method could also be used for the isolation of carboxypeptidase B from beef pancreas. PMID- 3109178 TI - Active centre studies on bovine pancreatic chymotrypsin with tripeptidyl-p nitroanilide substrates. AB - The kinetic behaviour of bovine pancreatic chymotrypsin was studied with 22 N protected and 17 N-unprotected tripeptidyl-p-nitroanilide substrates. The contribution of the individual side chains to the kinetic parameters were calculated by regression analysis. At subsite P1 (notation of Schechter and Berger, 1967, Biochem. Biophys. Res. Commun. 27, 157) Tyr seems to be better than Phe and Trp, concerning kcat values. At P2 subsite the best KM values were obtained with Gly and Ser, whereas the hydrophobicity of P2 subsite appears to be necessary for efficient catalytic activity. At P3 mainly polar amino acids, both with D and L configuration, were tested. They improve the solubility of substrates in aqueous medium, as well as the kinetic parameters. Suc(OMe) and Suc protecting groups at P4 increase significantly the catalytic activity compared to the aromatic ones. The obtained data were compared to the known substrate binding site of bovine pancreatic chymotrypsin. PMID- 3109179 TI - Mapping of the substrate binding site of human leukocyte chymotrypsin (cathepsin G) using tripeptidyl-p-nitroanilide substrates. AB - The kinetic constants, KM, kcat and kcat/KM of human leukocyte chymotrypsin (Cathepsin G, E.C.3.4.21.20.) were determined with 33 N-protected and 16 N unprotected tripeptidyl-p-nitroanilide substrates. The individual contributions of the amino acid side chains of the substrates at P1-P4 subsites to the kinetic parameters were calculated by regression analysis. As far as KM is concerned, the highest contributions yielded the structure of an "optimum" substrate PhCO-Ala Val-Tyr-pNA. The contribution values permitted us to characterize the S1-S4 binding segment in the enzyme's binding site, interacting with the P1-P4 moieties of the substrate. The enzyme prefers uniformly hydrophobic substituents at the S1 S4 sites. The S1 primary specificity subsite of the enzyme can bind Leu and 2 aminohexanoic acid as well, besides the aromatic amino acids Phe, Tyr, Trp. Data were compared with those obtained when studying pancreatic chymotrypsin with the same substrates. PMID- 3109180 TI - Chemical structure and biological activity relationship in bradykinin analogues containing proline-like unusual amino acids. AB - Ten different bradykinin analogues have been synthesized and tested for activity on isolated guinea-pig ileum. The results, in comparison with others in the literature, suggest some conclusions on a chemical structure - biological activity relationship. PMID- 3109181 TI - Temperature-induced spectral properties of chlorophyll a incorporated into egg yolk lecithin liposomes and lipo-protein complexes. AB - The temperature-induced fluorescence changes of Chl a in the systems consisting of albumin-egg-yolk lecithin and only lecithin were studied. As plotted against temperature in liposomes the fluorescence intensity of Chl a has a maximum at approximately 35 degrees C. In CLP complexes the curve profile for the fluorescence intensity versus temperature is sharper and the maximum occurred at a lower temperature (25 degrees C). No fluorescence maxima for ANS in liposomes and for Chl a in isotropic solutions were found. The second derivative absorption spectra of the investigated lipid systems exhibited bands which were characteristic of monomeric Chl a. We suggested that in the temperature zone studied Chl a in vitro is embedded within lipid bilayer rather than attached to the proteins. The occurrence of the fluorescence intensity maximum of Chl a in liposomes and lipo-protein complexes is related to the effects: temperature quenching of the fluorescence, Chl a-lipid interaction. PMID- 3109183 TI - Effect of glycerol on the low-temperature fluorescence spectra of green algae (short communication). PMID- 3109182 TI - Variations in acetylcholinesterase from brain and muscle of a freshwater air breathing teleost, Heteropneustes fossilis. AB - Specific staining on polyacrylamide gel of acetylcholinesterase (AchE) from brain and muscle of Heteropneustes fossilis showed one major tissue specific band in each. Eserine inhibited the enzyme competitively in both tissue homogenates. However, the normal level of activity and the pattern of the rate of inhibition with increasing eserine concentrations were different. Muscle showed higher AchE specific activity than brain. There was a hyperbolic increase in the percent of inhibition of AchE activity by eserine in muscle whereas in brain the pattern was biphasic. The apparent Km and Vmax in the two tissue homogenates were also different. The results suggest structural and functional variations of AchE in brain and muscle of H. fossilis. PMID- 3109184 TI - The value of routine cytologic examination of breast cyst fluids. AB - The results of the cytologic examination of 6,782 consecutive breast cyst fluids aspirated from 4,105 women during the period 1976 to 1983 were reviewed to assess the value of the routine cytologic study of such specimens. Cases in which cancer had been suspected by physical examination and/or mammography before aspiration of the cyst were excluded from the evaluation. Five clinically and radiologically inapparent intracystic papillomas were detected overall (0.1%). All cases of intracystic papilloma produced a blood-stained fluid and showed an intracystic mass at pneumocystography. Cytology was negative in two of these cases and falsely positive in one case while correctly identifying the papilloma in two cases. One incidental case of occult in situ lobular carcinoma was also detected. Routine cytologic examination of all breast fluids is thus not recommended as a cost-effective practice. Cytology should be used only when a blood-stained fluid is obtained (2% in the present series) since its indiscriminate application to all cyst fluids does not affect the rate of detection of intracystic lesions, most of which are suspected before the aspiration. PMID- 3109185 TI - Fine needle aspiration cytology of thymolipoma. A case report. AB - A case of thymolipoma in a 14-year-old girl diagnosed prospectively by fine needle aspiration (FNA) biopsy is reported. The cellular constituents of the aspirate, lymphocytes and epithelial cells, were characterized by routine cytology and immunocytochemistry. Although primarily based on the FNA cytology, the diagnosis was supported by the patient's clinical history and the radiographic demonstration of a fat density mass. This appears to be the first description of thymolipoma in a fine needle aspirate. PMID- 3109186 TI - Evidence for diverse structural variations of the forms of human FSH within and between pituitaries. AB - The biological activity of FSH in vitro (B-vitro) was compared with its radioimmunological (RIA) activity in 38 pituitary extracts from men and women. The B-vitro method was based upon the estimation of oestradiol produced by cultured Sertoli cells from 10-day-old rats. The mean B-vitro/RIA ratios for FSH of men and young and elderly women were almost identical. The mean values of median charge of the forms of FSH differed significantly between the three groups of human adults. The B-vitro/RIA ratio of different forms of FSH, separated by electrophoresis of 14 individual pituitary extracts, was higher for less negatively charged than for more negatively charged forms. Some forms of FSH with the same charge and separated from different pituitary extracts, e.g. from a young and an elderly woman, had significantly different B-vitro/RIA ratios. This ratio, thus, was not related to the charge per se of the hormone. However, the relation between the B-vitro/RIA ratio and the charge of FSH was similar for individual pituitary extracts when charge was expressed in relation to median charge. The results suggest that different molecular structural variations of FSH are involved in the polymorphisms observed within and between individual pituitaries. In human adults, the variation of FSH between the pituitaries mainly affects the metabolic clearance rate (MCR) of the hormone, whereas the variation within the individual pituitary affects both the MCR of the hormone and its biological effect at the target cell. PMID- 3109187 TI - Reduced ovarian follicular development as a consequence of low body condition in ewes. AB - The effect of body condition on ovarian follicular development was investigated in Scottish Blackface ewes in high and low body condition. Follicles were dissected from ovaries on days 11 and 12 of the luteal phase and 24 h after prostaglandin-induced luteal regression. Ewes in low body condition had a lower ovulation rate (low: 0.9; high: 1.8 P less than 0.05) and lower mean plasma levels of FSH during both the luteal (low: 54; high: 72 micrograms/l) and follicular (low: 34; high: 43 micrograms/l) phases of the cycle. Low body condition was associated with a reduced number of large (greater than or equal to 4 mm) follicles in both the luteal and follicular phases, and in low condition a lower proportion of these follicles was oestrogenic and potentially ovulatory as assessed by follicular fluid levels of oestradiol. However, within the different oestrogenic classifications of these large follicles there were no significant differences in the steroidogenic capacity as assessed by the concentrations of either oestradiol or testosterone in follicular fluid, basal and hCG-stimulated testosterone production, thecal 125I hCG binding or basal and testosterone stimulated oestradiol production by granulosa cells in relation to body condition. These results suggest that body condition influences ovulation rate by altering the concentration of FSH in blood, which in turn affects the number of potentially ovulatory follicles growing beyond 4 mm. PMID- 3109189 TI - Comparison of the malondialdehyde formation in megakaryocytes and platelets after in vivo and in vitro administration of aspirin. PMID- 3109188 TI - Increased luteinizing hormone sensitivity to dopaminergic inhibition in Graves' disease. AB - The effect of dopamine infusion (4 micrograms X kg-1 X min-1 from 9.00 to 13.00 h) on serum LH and FSH concentrations were studied in 15 patients (10 women, 5 men) with diffuse toxic goitre, and 10 healthy subjects (6 women, 4 men). Basal serum LH (17.0 +/- 0.8 IU/l) and oestradiol (women: 3.74 +/- 1.84; men: 3.05 +/- 0.77 pmol/l) were elevated in patients, whereas serum FSH and PRI were normal. Dopamine infusion did not modify serum FSH levels, but significantly depressed LH concentration in both hyperthyroid and healthy subjects. The LH decrement was more pronounced (P less than 0.01) in patients with Graves' disease (8.4 +/- 1.4 IU/l) as compared with controls (2.3 +/- 0.9 IU/l). There was a positive correlation between the maximum net decrease and the basal LH concentration (r = 0.95). The per cent decrease of LH levels in the hyperthyroid patients (54 +/- 4) was higher (P less than 0.001) than that in the controls. The finding of enhanced sensitivity to dopamine inhibition in thyrotoxic patients suggests that their inappropriately elevated serum LH levels may result in part from a reduced dopaminergic inhibition of LH secretion. PMID- 3109190 TI - Clinical studies on human alveolar macrophages. II. Functions of alveolar macrophages collected by bronchoalveolar lavage. PMID- 3109191 TI - Meet your colleague, the speech-language pathologist. PMID- 3109192 TI - Therapeutic contracts: a nursing tool. PMID- 3109193 TI - One method of reducing patient falls. PMID- 3109194 TI - A pressure sore monitoring program: just the beginning. PMID- 3109195 TI - Influence of clonazepam on cortical epileptogenic foci in the rat. AB - The antiepileptic action of clonazepam was studied on epileptogenic foci induced by penicillin in sensorimotor cortex in acute experiments in rats. Clonazepam (1 mg/kg intraperitoneally) only moderately decreased the frequency of interictal discharges of single cortical focus and delayed the propagation of discharges into the ipsilateral occipital region. On the contrary, clonazepam failed to influence the callosal projection of interictal discharges in single unilateral as well as in two symmetrical foci. Spontaneous transition of interictal discharges into ictal phases regularly seen when two symmetrical foci were formed was only delayed but not blocked by clonazepam. It may be concluded that clonazepam exhibits only a weak anticonvulsant action against cortical foci and against secondary generalization of epileptic activity. PMID- 3109196 TI - Carbon dioxide tensions in infants during mask anaesthesia with spontaneous ventilation. AB - Carbon dioxide tensions (PCO2) in arterialized capillary blood samples were measured in 39 infants anaesthetized for minor paediatric surgery. Anaesthesia was induced and maintained with oxygen, nitrous oxide and halothane, using a Mapleson-D system with spontaneous ventilation and a Rendell-Baker face mask. The duration of anaesthesia was between 15 and 95 min. Two capillary blood samples were obtained during stable anaesthesia before and after surgery. The PCO2 values varied between 3.7 and 8.0 kPa. The highest values were found in infants aged 15 30 days, 6.6 +/- 0.7 kPa (mean +/- s.d.), compared to 5.9 +/- 0.7 in infants aged 31-60 days, 5.6 +/- 0.8 in infants aged 61-180 days and 5.5 +/- 0.7 in infants aged 181-300 days. Comparison between measurements before and after surgery did not in any group indicate a progressive hypoventilation or a correlation between the length of the anaesthesia and the PCO2. It is concluded that anaesthesia with oxygen, nitrous oxide and halothane with spontaneous mask ventilation is a satisfactory method for minor procedures in infants over 1 month of age, while in younger infants controlled ventilation with intubation may be a safer choice of method. PMID- 3109197 TI - Change in tracheal blood flow during endotracheal intubation. AB - Changes in blood flow in the tracheal mucosa of the dog caused by the pressure exerted by high volume, low-pressure cuffs were measured with the hydrogen clearance method. Before inflating the cuffs, the blood flow of the tracheal mucosa was measured as a control for 12 h in order to confirm that the procedures of the hydrogen clearance method itself had little or no influence on the blood flow in the tracheal mucosa. After inflating the cuffs to create a tracheal wall pressure (TWP) of 1.3 kPa (10 mmHg), 2.6 kPa (20 mmHg), 3.9 kPa (30 mmHg) or 6.0 kPa (45 mmHg), local blood flows of tracheal mucosa (TBF) corresponding to each TWP were measured every hour for 12 h. No significant changes in blood flow were observed in the tracheal mucosa with the hydrogen clearance method before inflating the cuffs. In the groups with TWP of 1.3 and 2.6 kPa, the TBF rose 1 h after inflation of the cuffs, and then returned to the baseline values. In the group with TWP of 6.0 kPa, the TBF decreased markedly already 1 h after inflation of the cuffs, and continued to decrease severely thereafter. In the group with TWP of 3.9 kPa, the TBF followed an intermediate course between the groups with TWP of 2.6 kPa and 6.0 kPa. From the results of the present study, it was found that TBF was significantly impaired by a TWP of more than 3.9 kPa. Therefore, in prolonged intubation, TWP should be kept at or below 2.6 kPa. PMID- 3109198 TI - Smoking, age and the arterial-end-tidal PCO2 difference during anaesthesia and controlled ventilation. PMID- 3109199 TI - A new patient registration method for intensive care department management. AB - A new method to describe intensive care department performance is presented. The method is a complication of available administrative and medical data, completed with a severity of illness measure (Acute Physiology And Chronic Health Evaluation, APACHE) and the registration of nursing care intensity. The development of this latter patient stratification system (Intensive Care Activity Score, INCAS) is described. The performance of the method is demonstrated by a study of 200 consecutive admissions. PMID- 3109200 TI - Turning the mass-spectrometer into an easy to handle clinical instrument for routine multipatient surveillance of respiratory and anesthetic gases during anesthesia. AB - Although most authors use it as the reference instrument for respiratory gases measurement, the use of mass-spectrometer in clinical routine in ICU and in anesthesia remains quite limited. We developed a fully automatically controlled system, carrying on a twinned goal: The ACS-2000 (Automatic Calibration System) turns the Airspec MGA-2000 mass-spectrometer into a true clinical instrument, as easy to use as any routine monitoring instrument, and lets the clinician and the anesthetist benefit from its uncomparable metrological performances. PAMS-M, multibed monitoring system, shares the mass-spectrometer time among 4 to 8 rooms, providing each anesthetist with full composition of inspired and end tidal gases composition, trend evolution of those data, as with the display of capnogram. Each room is equipped with an IBM PC compatible intelligent terminal, abling the user to select the nature of the displayed information and enter into an easy menu driven dialog with the system. As a subproduct, the informatic infrastructure on which the system is based allowed, beyond the standard monitoring function, to set the bases of a computerized patient's anesthesia or respiratory monitoring report. PMID- 3109201 TI - Design of an automated system for assessing metabolic function in mechanically ventilated patients. AB - This paper describes the design of a fully automated self calibrated measurement system which can be connected to any commercial ventilator. The machine measures the oxygen consumption and carbon dioxide production. The instrument is based on commercially available analysers. An inexpensive microprocessor performs the computations, displays the results and leads the calibration's and measure's procedures. The apparatus is presently tested in clinical practice. PMID- 3109202 TI - Computerized prescription of total parenteral nutrition in pediatrics. AB - Total parenteral nutrition is often administered in pediatrics, especially to newborn infants and (very)-low-birth-weight infants. The use of a personal computer virtually eliminates errors, and removes the problem of tedious mathematical and time-absorbing calculations. The authors describe and discuss the TPN-program they developed. PMID- 3109203 TI - Muscle involvement during postnatal protein calorie malnutrition and recovery in rhesus monkeys. AB - The effect of protein calorie malnutrition (PCM) and, thereafter, nutritional rehabilitation on neuromuscular dysfunction was evaluated electromyographically, histopathologically and biochemically in 24 young, growing, healthy rhesus monkeys. There were 2 control and 2 PCM groups with 6 animals in each group. Animals of one control and one PCM group were killed at 10-12 weeks and those of the second PCM group were rehabilitated and killed together with the second control group at 20-22 weeks. The animals with PCM demonstrated irritability, muscular wasting, weight loss and reduced physical activity. The electromyographic findings showed a myopathic pattern revealed by significant reduction in motor unit potential duration and amplitude, and amplitude of interference pattern at maximum effort. The histopathological abnormalities were non-specific and consisted of rare obliterations of cross striations and streaming fibrillar appearance, mild increase in epimysial and perimysial tissue and 29-34% reduction in fibre size. A statistically significant reduction in motor nerve conduction velocity of median, ulnar, common peroneal and tibial nerves was found. The muscle Na and K were evaluated in all groups of animals. Muscle K content was reduced and Na concentration was augmented following PCM. The change in concentration of electrolytes within the fibres and reduction in the diameter of muscle fibres could be related to the observed functional alterations. These changes returned to normal in rehabilitated group. PMID- 3109204 TI - [Production of LIF and gamma interferon in patients with ragweed-induced allergic rhinosinusitis]. PMID- 3109205 TI - Etiology and diagnosis of neonatal conjunctivitis. AB - Chlamydia trachomatis was isolated from the most inflamed eye of 13 of 107 (12%) infants with neonatal purulent conjunctivitis and from none of 100 healthy infants (p less than 0.01). Staphylococcus aureus was recovered from 49 (46%) inflamed eyes and from 8 (8%) healthy eyes (p less than 0.01). Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, Escherichia coli and Klebsiella pneumoniae were isolated from very few infants with conjunctivitis but not from controls. No organisms could be recovered from 23 (22%) infants with conjunctivitis and from 60 (60%) healthy infants (p less than 0.01). The incidence of neonatal purulent conjunctivitis was 107 (2%), of 5,924 births. Eyes infected with C. trachomatis were significantly more inflamed than eyes from which S. aureus or no organisms could be isolated. Furthermore, conjunctival "pseudomembranes" were associated with C. trachomatis. The age at onset of the chlamydial conjunctivitis was higher compared to the age at onset of conjunctivitis in which S. aureus or no organisms were isolated. PMID- 3109206 TI - Impaired response of growth hormone-releasing hormone (GHRH) measured in plasma after L-dopa stimulation in patients with idiopathic delayed puberty. AB - In order to investigate the regulation of GH secretion in patients with idiopathic delayed puberty (IDP), either prepubertal (stage P1) or early pubertal (P2), GHRH levels in plasma were measured after stimulation with L-Dopa in a group of 16 patients with IDP. The results were compared to those obtained in 12 patients with constitutional short stature (CSS) at the same stages of puberty, who underwent L-Dopa test for insufficient height. Plasma GHRH levels were measured, after extraction and concentration on C18 Sep Pack columns, by radioimmunoassay using an antibody against 1-40 GHRH, which cross-reacts 100% with 1-44 GHRH. The sensitivity of the assay is 6-8 pg/ml. After L-Dopa intake, the peak of GH was mean +/- SEM 8.6 +/- 1.4 ng/ml in IDP and 12.0 +/- 0.8 ng/ml in CSS (NS). The peak of GHRH after L-Dopa was 41 +/- 10 pg/ml in IDP and 96 +/- 25 pg/ml in CSS (p less than 0.02). A significant (p less than 0.02) decrease of plasma GHRH peak values (mean +/- SEM 17.3 +/- 4.4 pg/ml) was noted in the five patients with IDP whose growth velocity was below -2 SD for their bone age compared to the patients with normal growth velocity (mean +/- SEM 75.0 +/- 14.5 pg/ml). These results suggest a hypothalamic dysfunction in patients with IDP, and a relationship between the well-known partial and transitory somatotropic deficiency found in some adolescents having a pubertal delay and their secretion of the releasing hormone GHRH. PMID- 3109207 TI - A comparative neonatal study of infants born by mothers with Chlamydia trachomatis in cervix uteri. PMID- 3109208 TI - Current research on recombinant human growth hormone and the related growth factors, IGF-1 and GRF. AB - A brief introduction is provided to the physiological actions of somatostatin, somatomedins and growth hormone releasing factor (GRF) in relation to human growth hormone (hGH). The development of recombinant DNA techniques allowed the biosynthesis of somatrem (methionyl hGH), and as the methods were refined, authentic recombinant hGH (methionyl-free) has been produced. rhGH is currently undergoing clinical trials in several countries. Recombinant IGF-1 has also been developed by similar methods, utilizing a yeast as the host cell. In contrast, GRF is too small to be biosynthesized, but can be produced by classical peptide synthesis. Only the N-terminal sequence is required for biological activity, and may be 29, 40 or 44 residues long. Research into the biological effects of both IGF-1 and GRF is underway. PMID- 3109209 TI - Another polysaccharide antigen of Eubacterium saburreum with heptose as the main constituent. AB - The polysaccharide antigen of Eubacterium saburreum strains L76, reacting by precipitation and complement-fixation, has D-glycero-D-galacto-heptose as the main component, and, in addition, O-acyl groups. PMID- 3109210 TI - Transient neocortical, hippocampal and amygdaloid EEG silence induced by one minute inhalation of high concentration CO2 in swine. AB - The study is part of a series of investigations performed with the ultimate goal of obtaining an objective evaluation of the ethical aspects and the narcotic efficiency of CO2 inhalation used as pre-slaughter anaesthesia for swine. Six Yorkshire swine were exposed twice to 80% CO2 for 1 min during simultaneous recording of the EEGs from the frontal neocortex, the dorsal hippocampus, and the amygdaloid region via permanently implanted electrodes. In five of the animals myoclonic jerks started at 28 +/- 1 s of CO2 exposure and lasted for 6 +/- 2 s. Neocortical slow wave (delta) activity and increased amplitude of the hippocampal theta (5-7 Hz) waves (i.e. EEG changes seen during the second stage of barbiturate anaesthesia) had developed before the brief period of myoclonic jerks. After this period the EEG activity gradually declined, resulting in neocortical EEG silence at the end of the exposure. This apparent isoelectricity lasted for on average 1 min. The return of the neocortical EEG activity exhibited a pattern reverse to its disappearance, but was much prolonged in comparison to the EEG extinction. Pre-exposure neocortical EEG pattern was not regained until 3 5 min post-exposure. In eight out of 11 experiments the CO2 inhalation also induced hippocampal EEG silence lasting for on average 30 s. EEG flattening was further obtained when recording from the amygdaloid nuclear complex and the adjacent pyriform cortex. The observed changes in the neocortical and hippocampal EEGs suggest that the present swine were unconscious already when they exhibited motor reactions. This does not exclude the possibility that CO2-independent stress/arousal factors present in a slaughterhouse environment may facilitate the development of motor phenomena similar to seizures, with the result that such reactions become manifest before the neocortical EEG exhibits an anaesthesia pattern. The duration of the observed EEG silence implies that, from the ethical point of view, exsanguination might safely be performed within 1 min after the moment when the animal is removed from the high concentration CO2. However, the slow return to a pre-exposure neocortical EEG pattern suggests that the swine remains unconscious for at least another minute. PMID- 3109211 TI - Leakiness of rat brain microvessels to fluorescent probes following craniotomy. AB - The effects of craniotomy and/or histamine treatment upon brain microvascular permeability was studied in Wistar rats. Extravasation of circulating Na fluorescein (MW 376) and of FITC-albumin (MW 69,000) was observed through a cranial window using intravital fluorescence microscopy. Simple exposure of the pial microvessels induced formation of discrete spots of fluorescent material around venules, but not around arterioles or capillaries. The average number of leaky spots to Na-fluorescein and to FITC-albumin was 4.3 and 1.8 per 10 mm2, respectively, 35 min after exposure. Pretreatment of the rats with either indomethacin (a cyclo-oxygenase inhibitor) or promethazine (a histamine H1 receptor blocker) did not reduce the number of leaky sites, whereas pretreatment with a combination of the two drugs had a significant protective effect. Administration of histamine (10(-4) M) to the exposed brain surface for 5 min increased the number of leaky sites to Na-fluorescein and FITC-albumin 3.2 and 3.6 times, respectively. It is concluded that exposure of the brain surface induces release of histamine and cyclo-oxygenase metabolites, and that these inflammatory mediators elicit formation of leaky sites in brain venules. PMID- 3109212 TI - Respiratory stimulant effects by TRH into the mesencephalic region in the rat. AB - Thyrotropin-releasing hormone (TRH) has previously been found to have a potent respiratory stimulant effect following intracerebroventricular administration. One part of the respiratory response, the shortening of inspiratory time, seems to be elicited from the raphe obscurus in the medulla. The prominent tachypnoea however is not elicited after local injections in the medullary region. In the present paper a micro-injection technique was employed to study respiratory actions of TRH in lightly anaesthetized rats kept in a whole body plethysmograph. Thyrotropin-releasing hormone in a dose of 100 ng per 0.5 microliter was found to induce an immediate tachypnoea after injections into the region of the interpeduncular nucleus of the midbrain. No effects on systemic circulation were seen. More rostral or dorsal sites of injection were without effect. The localization of the sites responsible for respiratory stimulation corresponds to the reticular activating system where electrical stimulation induces hyperventilation in cats. The tachypnoea might be closely related to the well known arousal effects of TRH. PMID- 3109214 TI - The role of the fibrinolytic system in thrombotic disease. PMID- 3109213 TI - Effector functions of macrophages. PMID- 3109215 TI - [Response of thyroid stimulating hormone (TSH) to TSH-releasing hormone (TRH) in chronic schizophrenia]. PMID- 3109216 TI - Menstrually-related mood disorders. PMID- 3109217 TI - Proteins and amino acids: effects of deficiencies and specific amino acids. AB - Information about effects of protein and amino acid intake on carcinogenesis comes mainly from experiments on laboratory animals. In general, tumor formation and tumor growth are retarded in animals consuming protein- or amino acid deficient diets, but the effects have been attributed mainly to reduced caloric intake or body weight. Nonetheless, some tumors grow well in animals consuming diets that contain levels of protein that are insufficient to meet their nutritional needs. Induction of tumors by chemical carcinogens or procarcinogens may be enhanced or inhibited in animals consuming a diet containing a particular level of protein, depending upon the responses of enzymes that activate or inactivate the specific compound being tested. The feeding of amino acid deficient diets or amino acid antagonists has been proposed as an adjunct to chemotherapy. Undoubtedly, tumor development and growth can be influenced by the quantity of protein consumed by an animal, but the responses observed with specific tumors and carcinogens may differ. Therefore, it is not possible to draw general conclusions about effects of protein intake on the incidence of cancer or on the process of carcinogenesis. PMID- 3109218 TI - Inhibition of chemical carcinogenesis and tumorigenesis by selenium. AB - Selenium is effective in inhibiting the incidence and total number of tumors resulting from treatment with various chemical carcinogens. This inhibition occurs both at the initiation and promotion phases of chemical carcinogenesis. At least part of the inhibition of the initiation stage is associated with changes in the metabolism of the parent carcinogen. Studies with 7,12 dimethylbenz(a)anthracene suggest that selenium specifically blocks the enzyme(s) responsible for the formation of anti-dihydrodiol epoxide adducts to DNA. Selenium is also effective in reducing the in vitro and in vivo growth of numerous neoplastic cells. However, differences in the sensitivity to selenium are evident in the various tumor cell lines that have been examined. Continuous selenium intake appears to be necessary to maximal inhibition in both models of carcinogenesis. Evidence suggests that selenodiglutathione or some other intermediate in selenium metabolism is responsible for the anticarcinogenic and antitumorigenic properties of this trace element. The mechanism by which selenium produces these effects is unknown, but it may relate to alterations in either RNA transcription or translation. These and other data strongly suggest that selenium is a naturally occurring anticarcinogenic and antitumorigenic agent. PMID- 3109219 TI - Use of combined monoclonal antibodies for the immunochemical determination of apolipoproteins A-I and B in human plasma. PMID- 3109220 TI - Regulation of human B lymphocyte activation, proliferation, and differentiation. PMID- 3109221 TI - The arrangement of immunoglobulin and T cell receptor genes in human lymphoproliferative disorders. AB - Immunoglobulin and T cell antigen receptor genes in their germ-line form are organized as discontinuous DNA elements that are joined by recombinations during lymphocyte development. The analysis of immunoglobulin gene structure and arrangement has been of great value in the study of human lymphoid neoplasms. The analysis of rearranged immunoglobulin and T cell receptor genes has been of value in defining the lineage (T or B cell) of neoplasms that were of controversial origin previously, determining the clonality of abnormal lymphocyte proliferations, diagnosing and monitoring the therapy of lymphoid malignancies, determining the state of maturation and the causes for failure of maturation of cells of the B cell series, and providing major insights into the cause of malignant transformation of B and T lymphoid cells. Thus, the application of this molecular genetic approach has great potential for complementing conventional marker analysis, cytogenetics, and histopathology, thus broadening the scientific basis for the classification, diagnosis, and monitoring of the therapy of lymphoid neoplasia. PMID- 3109222 TI - Biological activities residing in the Fc region of immunoglobulin. PMID- 3109223 TI - [Chromosomal investigation in infertile cases of azoospermia]. AB - Chromosomal examination in 85 patients with azoospermia revealed 62 patients (73%) with the karyotype 46, XY and 23 patients (27%) with other abnormal karyotypes. In this population, there were 17 patients with 47, XXY. Other anomalies were: 46, XYp+, 46, XXp+, 46, XYp-, 45, X, t (Ynf; 21), 45, XY, t (13q 15q), and 46, XY, r (18). Serum LH and FSH levels were high and testosterone level was low in the patients with 47, XXY compared with the other 6 patients (p less than 0.01). Also the mean value of testicular volume was low in the patients with 47, XXY (p less than 0.05). PMID- 3109224 TI - Morbidity of adult cranial irradiation. PMID- 3109225 TI - Systemic and coronary hemodynamic effects of combined intravenous diltiazem and nitroglycerin administration. AB - This study evaluated left ventricular (LV) and coronary hemodynamic effects of intravenous nitroglycerin (NTG) in the presence of an intravenous infusion of diltiazem in 15 patients with severe coronary disease. Diltiazem (250 microgram/kg bolus followed by 1.4 micrograms/kg/min infusion) alone decreased mean systemic blood pressure (mean 6%) without changing heart rate or LV end diastolic pressure. The rate of rise in LV pressure declined slightly (4%), and peripheral resistance decreased (19%). Coronary sinus (CS) and great cardiac vein (GCV) flows were preserved. Addition of NTG (average, 68 micrograms/min) decreased systemic pressure further (7%) as LV end-diastolic pressure declined (5 mm Hg). These pressure changes were accompanied by a 10% increase in heart rate (compared with the heart rate found with diltiazem alone). Peripheral resistance was similar to values after diltiazem alone. The CS and GCV flows did not decrease. The sequence of intravenous drug administration was reversed in three other patients with combination therapy, producing similar effects, regardless of which drug was administered first. Hemodynamic effects of intravenous diltiazem alone and its combination with intravenous NTG seemed potentially favorable for patients with ischemic heart disease. PMID- 3109226 TI - Carbon dioxide fiberoptic laser for treatment of coarctation of the aorta. PMID- 3109227 TI - Peak creatine kinase as a measure of effectiveness of thrombolytic therapy in acute myocardial infarction. AB - As part of the National Heart, Lung, and Blood Institute multicenter Thrombolysis in Myocardial Infarction Trial, the time to peak plasma creatine kinase (CK) activity as a marker of reperfusion in 272 patients with validated acute myocardial infarction was analyzed. Patients were treated with either tissue-type plasminogen activator or streptokinase by intravenous administration. All patients underwent acute coronary angiography. The infarct-related artery was identified and thrombolytic therapy administered. Reperfusion at 90 minutes was documented by angiography. CK was determined before institution of therapy and every 4 hours thereafter for the first 24 hours. Patients were classified into 3 groups for comparative purposes: group 1--occlusion with no reperfusion (n = 119); group 2--occlusion with reperfusion (n = 98); and group 3--subtotal occlusion (n = 55). Early (within 4 hours after treatment) and late (more than 16 hours after treatment) peaking of CK differentiated patients with drug-induced perfusion from those without reperfusion. Although peak CK between 5 and 11 hours after drug treatment did suggest perfusion through the infarct-related artery, it did not differentiate between drug-induced and spontaneous reperfusion. Clinically, early peak CK is a useful noninvasive means of assessing coronary artery patency. However, in clinical trials assessing drug therapy, the use of peak CK may overestimate drug effectiveness by including patients with spontaneous reperfusion. PMID- 3109228 TI - Efficacy of class Ib (lidocaine-like) antiarrhythmic agents for prevention of sustained ventricular tachycardia secondary to coronary artery disease. AB - The effects of lidocaine, tocainide and mexiletine were examined in 17 patients with coronary artery disease and chronic, recurrent, sustained ventricular tachycardia (VT) or ventricular fibrillation and inducible VT. Eleven patients presented with sustained VT; 6 patients had had an episode of sudden death from which they had been resuscitated. All patients were refractory to conventional antiarrhythmic agents. Lidocaine prevented induction of VT in only 3 patients (18%). Tocainide prevented induction of VT in only 1 lidocaine-responsive patient. Mexiletine prevented VT induction in 1 patient who had responded to lidocaine but not tocainide. Neither tocainide nor mexiletine was effective in preventing induction of VT in any patient who did not respond to lidocaine. Lidocaine terminated VT in 3 patients, but this did not predict noninducibility with lidocaine, tocainide or mexiletine. Cycle length of VT was prolonged slightly by lidocaine (control 311 +/- 14 ms, lidocaine 361 +/- 26 ms, p less than 0.05), tocainide (344 +/- 16 ms, p less than 0.05) and mexiletine (371 +/- 27 ms, mean +/- standard error of the mean, p less than 0.05). Thus, class lb agents are infrequently effective in preventing induction of VT in this group of patients, electrophysiologic inefficacy of lidocaine is highly predictive of continued inducibility with tocainide and mexiletine, and termination of VT with lidocaine does not correlate with its ability to prevent VT induction. PMID- 3109229 TI - Efficacy and safety of flecainide acetate for atrial tachycardia or fibrillation. AB - Thirty-nine patients with symptomatic ectopic atrial tachycardia (9 paroxysmal, of which 5 were incessant) and atrial fibrillation (AF) (25 paroxysmal, 5 chronic) were treated with oral flecainide acetate (100 to 400 mg/day). Thirty two patients had organic heart disease (16 coronary artery disease, 6 valvular, 10 cardiomyopathy, 7 primary electrical abnormality). Previous antiarrhythmic trials consisted of 0 to 5 drugs (mean 2.2). Of 39 patients with atrial tachycardia or AF, a complete response (no recurrent symptomatic atrial arrhythmia) was achieved in 22 (56%), a partial response (more than 95% reduction in arrhythmia occurrence) in 3 (8%) and no response in 14 (36%). Left atrial size, ejection fraction, underlying heart disease, duration of symptoms before treatment and drug levels were not useful for predicting clinical response. Therefore, during the follow-up period of 5.4 +/- 6.7 months (range 4 weeks to 2.5 years), flecainide had a complete or partial effect in 25 patients (64%). Complete or partial responses were noted in 8 of 9 patients (90%) with ectopic atrial tachycardia and 17 of 30 (57%) with AF. In 14 patients with concurrent ventricular arrhythmias, a significant reduction in episodes of nonsustained ventricular tachycardia was also achieved. Treatment was discontinued in 8 patients (20%) because of cardiac adverse reactions, including pulmonary edema and ventricular or atrial proarrhythmic response. Thus, oral flecainide acetate is effective therapy for some patients with ectopic atrial tachycardia or AF. PMID- 3109230 TI - Factors affecting the integrity of the intestinal mucosa of Gambian children. AB - The interrelationship between diarrhea, malnutrition, and small bowel integrity was investigated prospectively in 68 Gambian infants aged 0-18 mo. Profiles of growth and morbidity were recorded for 8 mo. Each month intestinal permeability was measured by the differential uptake of orally administered lactulose (L) and mannitol (M). In well infants the mean L:M ratio was 0.42 (range 0.11-1.42). This ratio was increased slightly for underweight (60-80% wt for age) infants (mean 0.52) but considerably for those with marasmus (less than 60% wt for age) (mean 1.3, p less than 0.001), for those with acute or chronic diarrhea (mean 1.0 and 2.85, respectively; p less than 0.001), or with measles (mean 1.4, p less than 0.001). Sequential studies of ward patients with malnutrition and diarrhea showed a rapid fall in L:M ratios with resolution of diarrhea. These studies suggest that damage to the small intestine may play an important part in the development of infant malnutrition in The Gambia. PMID- 3109231 TI - Parenteral (glucose or glucose-lipid) vs enteral repletion in malnourished primates: a controlled crossover study. AB - Nutritional repletion with glucose-based total parenteral nutrition (TPN), mixed substrate (58% lipid, 42% glucose) TPN, and mixed-substrate total enteral nutrition (TEN) was studied in four adult male chair-adapted primates using a crossover design. After 10 d nutritional depletion animals were repleted for 10 d with one of three isocaloric isonitrogenous diets. TPN Diets I and II were identical except that I provided all nonprotein calories as glucose while II provided 58% nonprotein calories as lipid and 42% as glucose. Animals were randomized to I or II as their first repletion treatment. The 20-d depletion repletion cycle was repeated with the other TPN diet after a 30-d rest period of caged free-feeding. After another 30-d rest period, animals underwent a third 10 d depletion and were repleted with 10 d of TEN (Diet III, identical to II in composition). The three diets resulted in similar weight gain, positive nitrogen balance and fluid balance, and increase in total iron-binding capacity. PMID- 3109232 TI - Molecular genotyping was not necessary. PMID- 3109233 TI - Misleading Rh phenotype and severe prolonged anemia in hemolytic disease of the newborn. PMID- 3109234 TI - How will diagnosis-related groups affect epidemiologic research? PMID- 3109235 TI - On the ability of birth defects monitoring to detect new teratogens. AB - Recent concerns have been raised about the ability of birth defects monitoring programs to detect increases in the incidence of birth defects following the introduction of new teratogens. The authors illustrate how most monitoring programs in the United States and Europe are limited in their ability to detect new teratogens because of a combination of parameters: the small population size, the low population frequency of exposure to the new teratogen, the weakness of many suspected teratogens (measured in terms of relative risk R), the low background rate, and the etiologic heterogeneity in the measured defects. In a system that monitors 25,000 births per year, it can be shown that although a new teratogen such as thalidomide (R = 175) can lead to a significant increase in the number of observed cases in 1-2 weeks of monitoring, even strong teratogens such as valproic acid and isotretinoin (R = 20-25) require more than 20 years of monitoring to show a significant increase in the number of cases because of low exposure frequency. Also, most mild to moderate teratogens (R = 2-5) can be totally missed. To improve the ability of birth defects monitoring programs to detect new teratogens, it is suggested that surveillance systems ought to examine subsegments of the population with maximal exposure potential, classify birth defects into more etiologically homogeneous groups, and expand the sample size of the monitored population. PMID- 3109236 TI - Epizootiology of Hantavirus infections in Baltimore: isolation of a virus from Norway rats, and characteristics of infected rat populations. AB - Rats trapped from 14 locations in Baltimore, Maryland, were shown to have antibody to Hantavirus. Antibody prevalence rates were higher in residential locations than in parks. Infected rats were obtained continuously over a six-year period from 1980-1985 at five locations, indicating the enzootic nature of this infection in urban rats in the United States. Prevalence of antibody and geometric mean titers increased with rat mass and sexual maturity, suggesting that infections in rats are acquired through age-related mechanisms. Three isolates of Hantavirus were obtained from rats. One of these isolates was shown by serologic tests and monoclonal antibody reactivity patterns to be similar, if not identical, to rat virus previously obtained from Philadelphia. The presence of rats in many urban settings and the high prevalence of Hantavirus infection in this species suggest that human exposure to this virus is occurring in the United States, although human disease from this exposure has not been recognized. PMID- 3109237 TI - Infectious hepatitis in dialysis patients. AB - Infectious hepatitis is a major problem for patients with end-stage renal disease and for staff caring for these patients. Initially hepatitis B was the major cause of hepatitis in dialysis patients and staff. Patients had a tendency to develop chronic hepatitis or become chronic carriers of the virus while staff either developed typical acute hepatitis or a primary antibody response. The discovery of the hepatitis B surface antigen (HBsAg), the screening of transfused blood for HBsAg, and the institution of infection control measures including isolation techniques have resulted in a remarkable decrease in the incidence of this disease. Nonetheless, the problem of infectious hepatitis continues as non A, non-B hepatitis has become more commonplace among dialysis patients. Unfortunately, no viral markers have been discovered, and blood products remain the major vehicle of transmission. The institution of infection control measures similar to those used to control hepatitis B has probably been effective in controlling the spread of this disease. It is hoped that the discovery of the etiologic agent(s), with the eventual goal of screening blood products and the development of a vaccine, will lead to full control of this disorder. PMID- 3109238 TI - Worsening hypokalemia and an acid-base abnormality in a pregnant woman. PMID- 3109239 TI - Economic impact of influenza. The individual's perspective. AB - The estimated average economic cost of influenza in the United States exceeds $1 billion each year, and the actual cost is more likely on the order of $3 to $5 billion per year. Benefit-cost models generally indicate that the benefits of influenza immunization for persons aged 65 and over outweigh the cost (when one excludes the cost of medical care in the additional years of healthy life gained by immunization). The low acceptance of influenza immunization suggests that individuals do not see the benefit-cost equation in the same way that policymakers do. This article presents a benefit-cost equation from an individual's perspective. The model demonstrates that pre-season immunization is cost-effective when the cost of a case of influenza, were it to occur, would be very high--as it is in persons under active medical care for heart or lung disease, for example. Immunization is also cost-effective for persons with a high income and a low cost of immunization--such as physicians themselves. The model further demonstrates that in the face of an actual epidemic, one can justify greater expenditures on protection against influenza, including immunization plus chemoprophylaxis or early chemotherapy. Finally, analysis of the model suggests the need for improved, less expensive systems for protecting individuals against influenza. PMID- 3109240 TI - Rabies pre-exposure prophylaxis using intradermal human diploid cell vaccine: immunologic efficacy and cost-effectiveness in a university medical center and a review of selected literature. AB - The authors studied the antigenicity of intradermal human diploid cell rabies vaccine administered to 40 laboratory workers considered to be at-risk at the University of Virginia Medical Center. A 1-year postvaccination serology was determined for 20 of those 40, all of whom demonstrated an antirabies titer greater than or equal to 1:50 by the raped fluorescent focus inhibition test. By 2 years' postvaccination, 5 of 40 subjects had "unprotective levels" (less than 1:5), whereas 35 had titers greater than or equal to 1:5, and none had a titer greater than or equal to 1:50. Booster doses given to four subjects whose titers had declined produced a 1-month postvaccination antirabies titer greater than or equal to 1:50 in all cases. Vaccine administration by the intradermal rather than the intramuscular route resulted in a cost savings of $120 (U.S.) per employee. This data indicate that the intradermal administration of human diploid cell vaccine for rabies pre-exposure prophylaxis achieves an immunologic response thought to be protective while providing a substantial cost savings when compared with the intramuscular route of administration. Those who receive primary pre exposure rabies vaccination should have serologic confirmation of immunologic protection every 2 years with a booster dose given to subjects demonstrating a titer less than 1:5. PMID- 3109243 TI - Reshaping nursing practice. PMID- 3109241 TI - Serologic evidence of acute murine typhus infection in a patient with culture negative endocarditis. AB - A patient with culture-negative infective endocarditis is presented in whom detailed serological studies were indicative of acute infection with murine typhus. The patient had aortic and mitral regurgitation with congestive heart failure and typical peripheral manifestations of subacute endocarditis, but no documented fever. Aortic and mitral valve replacement surgery and a 6-week course of doxycycline therapy produced a clinical cure in this patient, as well as a diagnostic fall in markedly elevated preoperative typhus indirect fluorescent antibody (IFA) and complement fixation (CF) titers. Serological studies were consistently negative for Q fever. PMID- 3109242 TI - A syndrome of microcephaly, eye anomalies, short stature, and mental deficiency. AB - We have studied a mother and son with a previously apparently undescribed syndrome of microcephaly, eye defects, small ears, mild mental deficiency, and short stature. The syndrome appears to be an autosomal or X-linked dominant trait. The cat eye syndrome, blepharophimosis or Kohn-Romano syndrome, Rieger syndrome, and other disorders are discussed in relationship to this entity. PMID- 3109244 TI - Improved pregnancy rate with monitoring of gonadotropin therapy by three modalities. AB - The frequency of complications during gonadotropin therapy was reduced after the introduction of rapid estrogen assays. However, pregnancy rates remained low especially in normoestrogenic women. One hundred forty-three infertile normoestrogenic women were treated with human menopausal gonadotropin-human chorionic gonadotropin for 661 cycles. Almost all cycles were ovulatory. Whereas 53.7% of the patients conceived when drug administration was monitored by cervical score and serum estradiol levels only, 72.1% became pregnant when treatment was monitored by these modalities and real-time ultrasonography of the ovaries (p less than 0.05). Mean serum estradiol levels were significantly higher when ultrasonography was used to monitor response, but complications such as multiple births and ovarian enlargement did not occur more often. The data suggest that "true" ovulation occurs more often when ovarian imaging is used to determine drug dosage. Because of the higher pregnancy rate achieved by combined clinical (cervical score), biochemical (serum estradiol), and sonographic methods of monitoring, this approach should replace less extensive techniques. PMID- 3109245 TI - Management of term breech presentation. AB - The management of 716 cases of singleton breech presentation occurring at 37 or more weeks of gestational age is reviewed. Beginning in 1980 a trial of external version was offered if the breech was identified before active labor. Only 433 (61%) breeches were identified before active labor. Of these, 171 (44%) underwent an attempt at external version and 83 (48%) were successful. The 623 cases remaining as breech presentation were stratified into three groups: cesarean section without labor (379), trial of labor with cesarean section (69), and trial of labor with vaginal delivery (175). The criteria for allowing a trial of labor are detailed. Careful review of maternal and fetal variables indicates that a trial of labor in selected patients will result in vaginal delivery in 72% and that this can be achieved without an increase in fetal or maternal mortality or morbidity. Furthermore, successful external version followed by a trial of labor in selected cases is highly cost-effective. PMID- 3109246 TI - Chronic bacterial endophthalmitis. AB - We studied a specific syndrome of uveitis secondary to intraocular bacterial pathogens of low virulence after extracapsular cataract extraction and intraocular lens implantation in three eyes. The onset of photophobia, visual impairment, conjunctival redness, and uveitis was delayed for four days to 12 weeks after surgery. Chronic inflammation persisted for five weeks to 16 months before a definitive diagnosis was made. Signs and symptoms were suppressed by administration of topical and systemic corticosteroids. Intraocular biopsy and antibiotic injection both established the cause as bacterial endophthalmitis and resulted in resolution of signs and symptoms. Staphylococcus epidermidis was cultured in two eyes and Achromobacter was cultured in one. PMID- 3109247 TI - Resolution of increased permeability pulmonary edema in rats. AB - The rate and sequence of interstitial and alveolar fluid removal from the lung after the occurrence of pulmonary edema were examined. Rats were given intraperitoneal injections of 20 mg/kg alpha-naphthylthiourea (ANTU), resulting in an increased permeability edema with alveolar flooding. Animals were killed at intervals between 2 and 48 hours after ANTU for the gravimetric determination of extravascular lung water (Qwl/dQl) and histologic study of the lung. Interstitial fluid volume was quantified by a morphometric technique. The assumptions were made that edema fluid equaled the experimental Qwl/dQl minus the normal Qwl/dQl, and that the edema fluid volume equaled the sum of interstitial and alveolar fluid volume. It was found that between 2 and 4 hours after the induction of pulmonary edema, fluid was removed from the alveolar space faster than it was removed from the interstitial space. Between 4 and 48 hours after ANTU, the fluid removal rate from both compartments was much slower, and interstitial fluid was removed at a faster rate than alveolar fluid. It is hypothesized that the later phase of fluid removal from the lung is dependent on the removal of protein. PMID- 3109248 TI - Role of sodium-calcium exchange in regulation of intracellular calcium in nerve terminals. AB - Ca efflux from rat brain presynaptic nerve terminals (synaptosomes) was examined after loading the terminals with 45Ca during a brief depolarization, usually in media containing 20 microM Ca labeled with 45Ca, to assure a small (physiological) load. Efflux of 45Ca was very slow in the absence of external Na and Ca (approximately 0.5% of the load/s) and was greatly accelerated by Na and/or Ca (presumably Na+-Ca2+ and Ca2+-Ca2+ exchange, respectively). The dependence of 45Ca efflux on external Na was sigmoid, with a Hill coefficient of approximately 2.5; this implies that more than two external Na ions are required to activate the efflux of one Ca ion. The external Na (Nao)-dependent Ca efflux was inhibited by 1 mM external La, by low temperature (Q10 congruent to 2.3), and by raising external K (to depolarize the synaptosomes). With small Ca loads, the mitochondrial uncoupler, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), had negligible effect on either Ca uptake or efflux; with large loads (greater than or equal to 5 nmol/mg protein), however, FCCP reduced the depolarization-stimulated Ca uptake and increased the Nao-dependent Ca efflux. These effects may be attributed to reduction of mitochondrial Ca sequestration. Mitochondria do not appear to sequester much Ca when the loads are smaller (and more physiological). Estimations of Ca efflux indicate that approximately 20% of a small 45Ca load (approximately 0.75 nmol Ca/mg protein) may be extruded via Na+ Ca2+ exchange within 1 s; this corresponds to a net Ca efflux of approximately 110 pmol Ca X mg protein-1 X s-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109249 TI - Covalent labeling of hydrosmotic toad bladder receptors with an antagonist of vasotocin. AB - A photoreactive analogue of vasotocin, [1-desamino,4-lysine(azidobenzoyl),8 arginine]vasotocin (4-N3-AVT), has been examined in the isolated toad urinary bladder for biological activity and binding to hormonal receptors. Although 4-N3 AVT induced only a small increase in bladder permeability to water, it behaved as a potent inhibitor of hydrosmotic action of [8-arginine]vasotocin (AVT) and [8 arginine]vasopressin (AVP). The inhibitory action of 4-N3-AVT was readily reversed on removal of the analogue from the serosal bathing solution. On the other hand, when bladders were exposed to 4-N3-AVT in the presence of long wavelength UV light (365 nm), the inhibition by 4-N3-AVT was not reversed on washout of the analogue. The dose of vasopressin required for a half-maximal response (ED50 value) was increased from 5 X 10(-9) to 1.3 X 10(-7) M in bladders photolabeled with 4-N3-AVT and the maximal response capacity of the tissue (intrinsic activity) was reduced to 79% of nonphotolabeled controls. A crude membrane preparation derived from bladders photolabeled with 4-N3-AVT contained 72 fmol of specific binding sites for tritium-labeled vasopressin per milligram protein, whereas nonphotolabeled controls had 136 fmol of specific binding sites per milligram protein. These observations suggest that 4-N3-AVT forms a covalent bond with hydrosmotic receptors in the presence of UV light. This is the first antagonistic photoaffinity analogue observed in the toad bladder and it may serve as a useful tool for analyzing the cellular mechanism of action of antidiuretic hormone. PMID- 3109250 TI - Multiple pathways for uptake of paraquat, methylglyoxal bis(guanylhydrazone), and polyamines. AB - The uptake of polyamines, methylglyoxal bis(guanylhydrazone) (MGBG), and paraquat [N,N-dimethyl-4,4'-bipyridylium] into control Chinese hamster ovary (CHO) cells and a mutant CHO cell line selected for resistance to the toxicity of MGBG was examined. In contrast to control CHO cells, the mutant cells had no detectable uptake of MGBG or any of the polyamines. There was no difference between the two cell lines in the uptake of alpha-aminoisobutyric acid (AIB), which indicates that there was no general change in membrane transport processes. The mutant cells were also found to be resistant to the toxicity of paraquat and to have a reduced capability to take up the herbicide. This finding confirms that the uptake of paraquat is necessary for the toxicity of this compound and that the paraquat is taken up by a transport system that also transports MGBG. Competition experiments showed that an excess of unlabeled paraquat inhibited uptake of MGBG and, to a lesser extent, uptake of putrescine and spermidine, but no inhibitory action on spermine uptake could be detected. Studies with type II cells isolated from rat lung also demonstrated uptake of paraquat and spermidine, but paraquat was only a weak inhibitor of spermidine uptake in this system. These results suggest that there may be multiple systems for the uptake of MGBG and polyamines and that paraquat is taken up by at least one but not by all of these systems. PMID- 3109251 TI - Hydroosmotic responses to short pulses of vasotocin by toad bladder. AB - When toads, Bufo marinus, were mildly dehydrated, the permeability to water of their urinary bladders increased, but blood samples placed directly on the wall of an isolated assay bladder did not contain enough arginine vasotocin (AVT) to induce the observed response. One explanation for this discrepancy is that AVT is secreted intermittently and rapidly cleared from the blood, even though the hydroosmotic response persists. The hydroosmotic response of bladders to pulsatile secretion of AVT was simulated by dipping isolated bladders for 1 min in Ringer's fluid with AVT followed by washout of hormone. Bladders developed the characteristic increase in membrane permeability to water several minutes after AVT had been removed from the serosal bathing solution. With short periods of bladder exposure to hormone, higher concentrations were required for triggering responses equivalent to those induced with continuous stimulation. This requirement was greater for vasopressin than it was for AVT. Studies with tritium labeled vasopressin indicated that there is a "receptor reserve" for the hydroosmotic action of vasopressin in the toad bladder. The magnitude of this reserve is reduced as the duration of stimulation with hormone is diminished. It is suggested that pulsatile exposure of the bladder to AVT increases the specificity of the hormone for hydroosmotic receptors and minimizes the development of target organ resistance. The large receptor reserve in this tissue may be required to capture short bursts of AVT secreted into blood, although this remains to be demonstrated. PMID- 3109252 TI - Stimulation of dog gastropancreatic hormone release by neuromedin B and its analogues. AB - The effects on gastrin, insulin, and glucagon release of neuromedin B (NMB), the C-fragment decapeptide of gastrin-releasing peptide-10 (GRP-10), seven analogues replacing amino acid positions 3, 6, and 9, and two C-terminal desamide analogues were examined in conscious dogs using intravenous bolus injection of these peptides study the structure-activity relationship of two bombesin-related peptides identified in mammals. The replacement from valine of position 6 of GRP 10 to threonine effectively reduced the stimulatory potency of these hormone secretions. Removal of the C-terminal amide of NMB and GRP-10 resulted in an almost complete loss of their stimulatory effect on gastrin secretion. [Leu3]GRP 10 elicited the most potent stimulatory activity on three hormone secretions among the analogues including NMB and GRP-10. These results indicate that valine in position 6 of GRP-10 and C-terminal amide of two peptides play an important role in the bioactivities of bombesin family peptides. PMID- 3109253 TI - Absorption and lymphatic transport of exogenous and endogenous arachidonic and linoleic acid in the rat. AB - [3H]Arachidonic (20:4) and [14C]linoleic acid (18:2) were fed to thoracic duct cannulated rats in test meals of either tracers alone, cream, Intralipid, pure arachidonic acid, or pure linoleic acid. Less [3H]20:4 than [14C]18:2 was recovered in chyle during the first 5 h. After cream feeding, the proportion of radioactivity found in phospholipids was high and increased during the first 3 h. After the meal (3-5 h) 61 +/- 6% of the 3H and 57 +/- 10% of the 14C was in phosphatidylcholine, and 11 +/- 3% of the 3H and 3.0 +/- 4% of the 14C was in phosphatidylethanolamine. Changing the fat vehicle to Intralipid or pure 18:2 decreased the proportion of label in the phospholipids and increased the 3H and 14C radioactivity in the triacylglycerol fraction, the distribution of 14C being influenced more than that of 3H. After feeding the tracers in 200 microliters of pure 20:4, greater than 90% of both isotopes was in triacylglycerol. During fasting, triacylglycerol transported 56% (0.7 mumol/h), phosphatidylcholine transported 34% (0.4 mumol/h), and phosphatidylethanolamine transported 10% (0.1 mumol/h) of the 20:4 mass. After cream or Intralipid feeding, the output of 20:4 containing phosphatidylcholine and phosphatidylethanolamine increased 2.1- to 2.8 fold, whereas the transport of 20:4 with triacylglycerol remained constant. Phospholipids thus became the predominant transport form for 20:4. After feeding 200 microliters of 20:4, the intestine produced, however, 20:4-rich triacylglycerols that transported 89% of the chyle 20:4. PMID- 3109254 TI - Mechanisms of lithium-vasopressin interaction in rabbit cortical collecting tubule. AB - In single cortical collecting tubules (CCT) of the rabbit, guanosine 5' triphosphate (GTP) increased the arginine vasopressin (AVP)-stimulated adenylate cyclase (AC) by 60% (P less than 0.05). In contrast, guanosine 5' O-(2-thio) diphosphate (GDP-beta S), a competitive inhibitor of GTP action on the stimulatory guanine regulatory protein (Ns), reduced the AVP-stimulated AC activity by 72% (P less than 0.001), indicating the presence of endogenous GTP in the cells under study. That inhibitory effect was reversed by the addition of GTP to the incubation medium. In isolated perfused CCT, cholera toxin (CT) induced a significant increase in water permeability in the absence of AVP. In contrast, Bordetella pertussis toxin (BPT) did not modify the low AVP-independent water permeability. Lithium, an inhibitor of the hydrosmotic action of AVP, also inhibits the hydrosmotic action of CT by 70% (P less than 0.05) but not that of forskolin. The conclusions of the present study are Ns is required for AVP stimulation of AC in the CCT; Ns is functionally active in this system as evidenced by the hydrosmotic effect of CT; the lack of effect of BPT suggests that the low AVP-independent water permeability in the CCT is not the result of a tonic inhibition of the AC operating through the inhibitory guanine nucleotide regulatory protein; and the inhibition by lithium of the hydrosmotic action of AVP in the CCT appears to involve an interaction with the regulatory proteins (probably Ns) or with their binding to the catalytic unit of AC. PMID- 3109255 TI - Luminal disequilibrium pH and ammonia transport in outer medullary collecting duct [corrected and issued with original paging in Am J Physiol 1987 Aug;253(2 Pt 2)]. AB - We measured bicarbonate, ammonia, and luminal pH in segments of the rabbit outer medullary collecting duct (OMCD) to determine the relationship between luminal pH and ammonia transport. Both the inner-stripe and outer-stripe portions of the OMCD absorbed bicarbonate at high rates. The outer stripe OMCD generated an acidic pH disequilibrium that was reversibly dissipated by exogenous luminal carbonic anhydrase. In contrast, the inner stripe OMCD did not generate a spontaneous pH disequilibrium unless perfused with the carbonic anhydrase inhibitor acetazolamide. Ammonia secretion was three times more rapid in the outer stripe OMCD than in the inner stripe OMCD. We conclude the following. 1) Both the inner-stripe and outer-stripe portions of the rabbit OMCD secrete protons at substantial rates. 2) Functional luminal carbonic anhydrase is present in the inner stripe OMCD but absent from the outer stripe OMCD. 3) Ammonia secretion occurs predominantly by NH3 diffusion in both portions. 4) The luminal pH disequilibrium, which is normally present in the outer stripe OMCD, enhances ammonia secretion. PMID- 3109256 TI - Reflex regulation of atrioventricular conduction. AB - We evaluated the time course of baroreflex modulation of atrioventricular (AV) nodal conduction in anesthetized dogs (n = 28). Beat-by-beat changes in heart rate (HR) and AV interval (AVI) evoked by transient alterations in arterial pressure (AP) were recorded in the intact state, after vagotomy, and following stellectomy. Under each experimental condition, alterations in AP induced parallel changes in HR and AVI with maximum HR and AVI responses occurring simultaneously. In three animals, AP alterations elicited pacemaker shifts that markedly altered AVI. Reflex changes in AVI were also examined during atrial pacing. When pacing at a low (120 beats/min) versus a high (190 beats/min) level of heart rate, reductions in AP decreased AVI to a significantly lower absolute value in the intact state, after vagotomy, and following stellectomy. However, under each experimental condition, decreases in AP elicited marked changes in AVI at either level of pacing. We conclude that baroreflex-induced changes in sympathetic and parasympathetic activity influence the sinoatrial and AV nodes simultaneously, predominate over the effects of changes in HR at the AV node, and may induce pacemaker shifts that influence the measurement of AVI. PMID- 3109257 TI - Vasomotor properties of immature canine coronary collateral circulation. AB - This study examined the ability of the immature coronary collateral circulation to undergo vasodilation in response to nitroglycerin and vasoconstriction in response to alpha-adrenoceptor stimulation. Studies were performed in 12 anesthetized dogs. Collateral flow was estimated from measurements of retrograde flow from the acutely ligated and cannulated anterior descending branch of the left coronary artery. Antegrade flow into the collateral-dependent myocardium was minimized by embolizing the anterior descending artery with 25-microns microspheres. Drugs to be tested were introduced into the left main coronary artery to reach collateral vessels arising from the left circumflex and septal arteries. Intracoronary administration of nitroglycerin (6 micrograms X kg-1 X min-1) resulted in a 33 +/- 7.7% increase in retrograde blood flow (P less than 0.01) and a 23 +/- 3.8% decrease in calculated collateral resistance (P less than 0.01). No significant change occurred in retrograde blood flow or calculated collateral resistance during cardiac sympathetic nerve stimulation after beta adrenergic blockade with propranolol, selective alpha-adrenergic stimulation with phenylephrine (1 microgram X kg-1 X min-1), or selective alpha 2-stimulation with BHT 933 (2 micrograms X kg-1 X min-1). Thus, the immature coronary collateral circulation was capable of active vasomotion, as demonstrated by vasodilation in response to nitroglycerin, but did not undergo vasoconstriction in response to alpha-adrenoceptor stimulation. PMID- 3109258 TI - Renal pressor reflex: involvement of sympathetic vasoconstrictor mechanisms. AB - We examined whether vasopressin and/or sympathetic vasoconstrictor mechanisms constitute the efferent limb of an afferent renal nerve (ARN)-dependent renal pressor "reflex" produced by acute unilateral renal artery stenosis (RST). Rats that had received sinoaortic denervation (SAD) were implanted with right renal artery occluders and flow probes. After recovery, conscious rats received captopril. Acute RST increased arterial pressure (AP) by 25% and mesenteric and hindquarters resistances by 35 and 51%, respectively. Vasopressin receptor antagonism was without effect on the reflex. Ganglionic blockade (chlorisondamine or trimethaphan) abolished the reflex, as did alfaxalone/alfadolone or urethan chloralose anesthesia. In an additional study, SAD animals were prepared with chronic T6 spinal cord transection. Increases in AP during RST were unaffected by spinal transection (27 +/- 4 mmHg). However, the increase in hindquarter resistance in the sham-transected animals (57 +/- 12%) was markedly attenuated (19 +/- 4%) in the spinal-transected group. The data suggest that in animals with depressed baroreflexes and renin-angiotensin system responsiveness, acute RST initiates an ARN-dependent pressor reflex with vasoconstrictor nerves comprising the efferent limb of the reflex. The reflex can be integrated at the spinal level and is highly sensitive to anesthesia. PMID- 3109259 TI - Oxygen metabolites and vasodilator mechanisms in rat cremasteric arterioles. AB - The effects of oxygen metabolites (superoxide anion and hydrogen peroxide) on male Wistar rat cremasteric arterioles and the involvement of these species in the mechanism of vasodilation to arachidonic acid and bradykinin were examined by in vivo television microscopy. In the present study, xanthine oxidase-derived oxygen metabolites from endogenous substrates elicited vasodilation that was selectively and almost completely inhibited by catalase but not by superoxide dismutase. These findings implicate hydrogen peroxide as the vasoactive metabolite generated. Topical application of hydrogen peroxide itself on cremasteric arterioles caused concentration-dependent dilation over the range of 10(-7) to 10(-4) M. Responses to hydrogen peroxide concentrations of up to 10(-5) M were completely inhibited by indomethacin, suggesting that hydrogen peroxide induced increases in vessel diameter are primarily mediated through the production of vasodilator prostaglandins. In this study, we have not found any evidence to suggest that dilator responses to arachidonic acid or bradykinin are mediated through the extracellular generation of oxygen metabolites. Hydrogen peroxide-induced vasodilation might be involved in the events linking the sensing of oxygen tension through intracellular peroxide formation to the production of vasoactive mediators in the cremasteric microcirculation. PMID- 3109260 TI - Transfer of nonelectrolytes from blood into peripheral nerve endoneurium. AB - Permeability-surface area (PA) products were determined for the transfer of seven nonelectrolytes across the blood-nerve barrier (BNB) of rat tibial nerve using a quantitative in vivo injection technique. PA values at the BNB for slowly penetrating nonelectrolytes such as urea, mannitol, L-glucose, and sucrose differed by less than threefold from values at the blood-brain barrier in the same animals. Permeability coefficients for transfer across the BNB were calculated assuming both endoneurial capillaries and perineurium contribute to solute flux into endoneurium. Total BNB surface area was determined as 175 cm2/g with morphometric techniques. Calculated permeability coefficients for slowly penetrating nonelectrolytes ranged from 7 X 10(-8) cm/s for sucrose to 4 X 10(-7) cm/s for urea and were directly proportional to solute lipid solubility as measured by the octanol-water partition coefficient. BNB permeability coefficients for sucrose, mannitol, L-glucose, and urea were within 60% of values at cerebral capillaries, of the same order of magnitude as values at aporous lipid membranes, and 100-1,000 times less than values at most nonneural capillaries, such as in skeletal muscle. These results demonstrate that the BNB markedly restricts the transfer of hydrophilic nonelectrolytes between plasma and endoneurium and that diffusion restriction of the BNB is comparable to that of the blood-brain barrier. PMID- 3109261 TI - Myocyte and endothelial injury with ischemia reperfusion in isolated rat hearts. AB - We determined the time course of ischemic injury, the effects of reperfusion, and the protective effects of prostacyclin, oxygen radical scavengers, and diltiazem on myocardial myocyte and endothelial cell functions in isolated rat hearts. Left ventricular power and coronary microvascular permeability were used as indexes of myocyte and endothelial cell function, respectively. Neither 5- nor 10-min ischemia reperfusion significantly changed power or permeability. However, with reperfusion following 20 and 30 min of ischemia, power was reduced 50 and 60% and permeability increased 70 and 90%. In 30-min ischemic hearts the ischemia-induced increase in permeability was apparent after 4 min reperfusion and further exacerbated at 20 min. Hypoxic reperfusion did not prevent increased permeability. Prostacyclin or a combination of superoxide dismutase, catalase, and mannitol also did not prevent increased permeability, and the radical scavengers did not ameliorate depressed power. In contrast, perfusion with diltiazem during ischemia reperfusion blunted the reduction in power and prevented the increase in permeability. We conclude that ischemia reperfusion causes similar time course of injury to myocytes and endothelial cells; reperfusion contributes to endothelial injury, and diltiazem affords protection to both cell types. PMID- 3109262 TI - Effect of blood pressure on medial medulla-induced muscle atonia. AB - Stimulation of the medial medullary reticular formation (MMRF) has long been reported to produce generalized inhibition of skeletal muscle activity. However, several studies have reported that in most cases MMRF stimulation produces only increases in muscle tone. In the present investigation we have found that blood pressure is a critical variable, determining whether MMRF stimulation will produce muscle excitation or inhibition. When mean arterial pressure (MAP) was greater than 80 mmHg but less than 148 mmHg, MMRF stimulation produced muscle antonia. Reductions of blood pressure by pharmacological or mechanical techniques induced a reversal of response to MMRF stimulation; stimulation that produced inhibition in base-line conditions produced excitation after MAP reduction. MAP reductions of as little as 10% could cause the reversal response. In contrast, the EMG reduction to MMRF stimulation was not changed or was augmented when MAP was raised. MMRF induced atonia, and its reversal by blood pressure reduction persisted after bilateral isolation of the carotid sinus combined with vagotomy, and in the 6-hydroxydopamine-treated cat. Spinal transection at the cervicothoracic junction did not block atonia or the reversal response. It is suggested that the reversal is mediated centrally. PMID- 3109263 TI - Ventral medullary surface inputs to cervical sympathetic respiratory oscillations. AB - To examine the effects of focally cooling three areas (rostral, intermediate, and caudal) of the ventral medullary surface (VMS) on respiratory oscillations in cervical sympathetic and phrenic nerve activity, 12 cats were anesthetized, vagotomized, paralyzed, and artificially ventilated with 7% CO2 in O2. Cooling the intermediate area from 37 to 20 degrees C significantly reduced the magnitude of respiratory oscillations in both cervical sympathetic activity (P less than 0.001) and phrenic activity (P less than 0.001). Graded cooling of all three areas caused graded reductions in sympathetic respiratory-related activity that were comparable to the reductions in phrenic activity. The magnitude of the reductions in sympathetic respiratory oscillations was greatest for the intermediate area, followed in order by the caudal and rostral areas. Eight cats also underwent graded VMS cooling while ventilated with 3% CO2 in O2 and 100% O2. At each level of inspired CO2, graded cooling resulted in graded reductions in respiratory oscillations in sympathetic activity; conversely, at each medullary temperature, graded increases in inspired CO2 caused graded increases in cervical sympathetic respiratory activity. These results suggest that all three areas of the VMS influence respiratory oscillations in cervical sympathetic activity, although to different extents. PMID- 3109264 TI - Partial purification and characterization of cysteine proteinases in eccrine sweat. AB - Attempts were made to purify and characterize cysteine proteinases in human eccrine sweat and further clarify their origin. Benzoyl-DL-arginine-beta naphthylamide (BANA) and L-leucine beta-naphthylamide (LeuNA) hydrolases in thermally induced sweat were sequentially purified by Sephacryl S-200 chromatography and chromatofocusing, which yielded two major peaks of BANA hydrolase activity, BANA-I and BANA-II. Both enzymes are cysteine proteinases as evidenced by stimulation of enzymic activity by dithiothreitol and ethylenediaminetetraacetic acid and its inhibition by iodoacetic acid, (PCMB), and trans-epoxysuccinyl-L-leucylamido-(4-guanidino)-butane (E-64). Unlike BANA II, BANA-I showed an additional aminopeptidase activity, an affinity to concanavalin A-Sepharose but no affinity to organomercurial sepharose and failed to hydrolyze benzyloxycarbonyl-phenylalanyl-arginine 4-methyl 7-coumarylamide (Z Phe-Arg-NMec), a specific substrate for cathepsin B, which is poorly sensitive to leupeptin [inhibitor constant (Ki) = 1 X 10(-5) M] and relatively heat resistant. These and other characteristics such as its isoelectric points (PI) (= 5.8) and the Km for Arg-NMec (0.1 mM) and BANA (0.71 mM) all support the possibility that BANA-I is closely related to cathepsin H. In contrast, BANA-II is sensitive to Zn2+, leupeptin (Ki = 5.5 X 10(-9) M), is not adsorbed by concanavalin A- (Con A)Sepharose, but is bound to organomercurial sepharose. It has a specificity to Z Phe-Arg-NMec but not to Arg-NMec, has the molecular weight of 27, PI of 5.2, the pH optima for BANA (6.0), and the Km for BANA of 3.3 mM and the Km for Z-Phe-Arg NMec of 0.1 mM. These features resemble those of liver cathepsin B. Leupeptin sensitive BANA hydrolase was observed in the glandular extract of isolated sweat glands, which was increased after stimulation with methacholine and isoproterenol in vitro. The data are consistent with the notion that cathepsins B- and H-like enzymes are present in eccrine sweat and the former may be derived from the sweat gland. PMID- 3109265 TI - Reduction of CO2-induced anxiety in patients with panic attacks after repeated CO2 exposure. AB - The authors compared the subjective reaction of 13 panic patients and eight control subjects to a 35% CO2 challenge, a treatment known to produce physical symptoms comparable to those of natural or lactate-induced panic, and to placebo treatment (inhalation of air). They found that patients had higher placebo scores than control subjects, patients tended to get highly anxious on CO2 and control subjects did not, and CO2-induced subjective anxiety in patients decreased as the number of CO2-induced exposures to interoceptive anxiety symptoms increased. The data support a behavioral account of the effects of anxiogenics. PMID- 3109266 TI - Promoting preventive care: changing reimbursement is not enough. PMID- 3109267 TI - The initial effects of the prospective payment system on nursing home patients. AB - We examined the discharge outcomes and admission characteristics of patients admitted to Southern California skilled nursing facilities (SNFs) for the first time following an episode of hospitalization in 1980, 1982-83 (all pre prospective payment system), and all admissions during July through September 1984 (post-prospective payment). The proportion of patients covered by Medicare on admission was 18 per cent in 1980, 36 per cent in 1982-83, and 57 per cent in 1984. For patients discharged within 30-60 days to SNFs, in all three time periods more Medicare than non-Medicare patients were bed-bound, had indwelling catheters, and were comatose. There were only modest case-mix differences between the groups and no changes over time in discharge outcomes, including the proportion dying in the SNF, or being returned to a hospital. The time-related changes that were found preceded the implementation of the diagnosis related group (DRG) based prospective payment system. PMID- 3109268 TI - Predicting charges for inpatient medical rehabilitation using severity, DRG, age, and function. AB - We examined the effectiveness of using diagnosis related groups (DRGs), Severity of Illness Index (SII), age and function at admission to predict inpatient charges for medical rehabilitation. Data from our sample of 199 indicate that DRGs alone explained approximately 12 per cent of the variation in charges for inpatient rehabilitation while SII explained 26 per cent of the variation. SII, DRG, and age together yielded the highest regression coefficient, accounting for nearly 39 per cent of the variation in total charges; SII and age accounted for 36 per cent of the variation. Within DRG categories, SII was the only important predictor of inpatient charges accounting for 23 per cent of the variation in charges among stroke patients (DRG 014) and 28 per cent of the variation in charges among hip fracture patients (DRG 210). Function at admission was not a useful predictor of inpatient rehabilitation charges within DRGs. These results suggest that SII and age may be useful in developing a DRG-based prospective payment system for inpatient medical rehabilitation. PMID- 3109269 TI - Indications for needle catheter jejunostomy in elective abdominal surgery. AB - Needle catheter jejunostomy for postoperative nutritional support is now employed worldwide. However, there is a large discrepancy regarding indications for this technique which this study attempts to rectify. The need for nutritional support after elective abdominal procedures in 464 patients was analyzed and compared with the experience with needle catheter jejunostomy in 42 patients. The results show that needle catheter jejunostomy is indicated after extensive operations of the upper gastrointestinal tract, for example, esophagectomy, total gastrectomy, and the Whipple procedure. With minor upper gastrointestinal operations, or procedures of the lower gastrointestinal tract, needle catheter jejunostomy should be performed only in patients with poor nutritional status or in the presence of postoperative chemotherapy or radiotherapy. In an unclear situation, liberal insertion of the needle catheter jejunostomy and a postponed decision on enteral feeding is recommended, as there is no significant catheter-related morbidity. PMID- 3109270 TI - [Comparative immunochemical study of the system of soluble leukocyte antigens in women with chronic salpingo-oophoritis in the remission stage]. PMID- 3109271 TI - Evaluation of gonadal function following long-term treatment for acute lymphoblastic leukemia in girls. AB - Twenty-four girls were studied following long-term treatment (mean: 50 months) for acute lymphoblastic leukemia; 14 were prepubertal and 10 pubertal. Follow-up during endocrine studies ranged from 2 months to 6.7 years (mean: 2.3 years). Five of 14 prepubertal patients started clinical pubertal development at a normal age and were reevaluated during puberty, increasing the pubertal group to 15 patients. Thirteen of 15 pubertal patients had received cranial radiotherapy. Ten of 15 pubertal patients started menses during the endocrine study. Although age of menarche was normal, in nine patients it was below the normal mean. Except for the remaining patient, all had received cranial cobalt therapy. In 6 of 19 patients bone age was significantly accelerated. Serum gonadotrophin response to LH-RH was normal in 13 prepubertal patients and in 10 pubertal patients. In 3 of 10 pubertal patients follicle-stimulating hormone (FSH) values were temporarily elevated. Only one pubertal patient had oligoamenorrhea. Five patients were studied by measuring serum progesterone on days 19-22 of the cycle to determine corpus luteum function. Three of them showed progesterone levels compatible with adequate corpus luteum function (6, 19, and 12 ng/ml, respectively) and two presented low progesterone levels (2 ng/ml), probably because of their short gynecological age (0.24 and 0.3 years, respectively). This study suggests that neither the disease nor the long-term antileukemia therapy seems to injure gonadal function in girls. A tendency to early sexual development was observed, which may be related to cranial cobalt therapy. PMID- 3109272 TI - Cost-effectiveness of neonatal IgE-screening for atopic allergy before 7 years of age. AB - Obvious atopic diseases developed in 18% of 1651 non-selected children before 7 years of age. More than 80% of newborns with high IgE concentrations in cord blood developed atopic diseases before this age. Although the sensitivity of the IgE test is rather low (40%), most cases (94%) of severe, long-lasting atopic disease show a high neonatal IgE concentration, and the specificity of the test is high (94%). Calculations of total costs of screening were made on the basis of family history alone compared with neonatal IgE-screening in two groups: all newborn infants, or infants with a family history of atopic disease. The cost of preventive measures and treatment costs were included in the calculations. Results were compared with the cost of conventional treatment. Provided that preventive measures delay onset of symptoms in atopic-risk subjects (and assuming total patient compliance) then IgE-screening was cost-effective in both groups, which screening solely on a basis of family history was not. In Sweden there was a total saving of approx. 20 million SEK or 3 million US$ per annum. Thus, IgE screening of cord blood to select newborns for preventive measures is also economically worthwhile. PMID- 3109273 TI - [Description of a treatment technic using a CO2 laser in a lymphangioma of the upper aerodigestive tract]. PMID- 3109274 TI - Arterial to end-tidal carbon dioxide tension difference during anaesthesia for tubal ligation. AB - Twenty-nine patients scheduled for postnatal tubal ligation by minilaparotomy under general anaesthesia were studied. Arterial and end-tidal carbon dioxide tensions were determined during anaesthesia. The mean arterial to end-tidal carbon dioxide tension difference was 0.08 kPa (SEM 0.05). Thirty-one percent of the patients had negative values. These results were similar to those observed during Caesarean section. The physiological changes responsible for reduced arterial to end-tidal carbon dioxide values, persist into the postnatal period. It is predicted from the regression analysis of the time between delivery and anaesthesia for tubal ligation and arterial to end-tidal CO2 difference, that the values might return to normal nonpregnant levels by 8 days following delivery. PMID- 3109275 TI - Carbon dioxide laser bronchoscopy. A review of problems and complications. AB - The records of 20 patients who underwent carbon dioxide laser bronchoscopy were analysed retrospectively. Many of the cases presented with evidence of severe obstruction of the trachea or major bronchi and were regarded as highly at risk from anaesthesia. The majority of problems in the 35 laser sessions related to the use of a rigid bronchoscope for delivering the laser and to the ventilatory difficulties associated with the airway pathology. Invasive arterial monitoring for blood gas analysis and blood pressure measurement proved essential to detect and correct changes of a potentially serious nature. This experience is compared and contrasted with that of others. PMID- 3109276 TI - Sampling for carbon dioxide. PMID- 3109277 TI - Toxic organic compound recoveries from 2,6-diphenyl-p-phenylene oxide porous polymer using supercritical carbon dioxide and thermal desorption methods. PMID- 3109278 TI - Determination of polychlorinated biphenyls using multiple regression with outlier detection and elimination. PMID- 3109279 TI - Routine determination of organochlorine pesticides and polychlorinated biphenyls in human milk using capillary gas chromatography-mass spectrometry. PMID- 3109281 TI - Monoclonal IgM and chronic urticaria: two cases. AB - We report two patients with chronic urticaria and serum monoclonal IgM without detectable lymphoid disease. In the 14 cases previously reported, clinical, histologic, and immunologic characteristics appeared very similar. The pathogenesis of this peculiar entity is discussed. PMID- 3109280 TI - Nasal allergy: a risk factor for middle ear disease. PMID- 3109282 TI - [Critical study of the value of capnography in anesthesia]. PMID- 3109283 TI - [Generalized seizure induced by methohexital]. AB - Seizures induced by methohexitone have been reported in epileptic patients. An alcoholic patient without any previous history of epilepsy had grand mal-like seizures after being given an intravenous injection of 4 mg X kg-1 methohexitone. The respective parts played by high doses of methohexitone and chronic alcoholism in the induction of seizures are discussed. PMID- 3109284 TI - [Non-cardiogenic pulmonary edema associated with severe diabetic ketoacidosis]. AB - Non cardiogenic pulmonary oedema occurs rarely in patients with diabetic ketoacidosis, except in conjunction with an infection. A case is reported of non cardiogenic pulmonary oedema in a patient with severe diabetic ketoacidosis, which resolved within 72 h with oxygen supply only. There were no objective facts which could explain its pathogenesis, despite the important pulmonary asymmetry due to a unilateral diaphragmatic paralysis. PMID- 3109286 TI - Effect on the seizure threshold in dogs of tocainide/lidocaine administration. AB - Oral lidocaine analogues, such as tocainide, recently have been introduced to treat cardiac arrhythmias. The side effects of tocainide are similar to those of lidocaine, but possible interactions with lidocaine have not been examined thoroughly. With the increased use of these agents, emergency physicians must decide the safety of concurrent administration of lidocaine for local anesthesia or arrhythmia management. Twelve dogs were assigned randomly to either a lidocaine (L) or a tocainide/lidocaine (TL) group. The L group received lidocaine at a dosage of 0.5 mg/kg/min until the animals seized. The TL group received both loading and maintenance doses of tocainide to obtain therapeutic steady-state tocainide levels prior to receiving lidocaine at a dosage of 0.5 mg/kg/min. Venous blood samples to measure drug levels were obtained at 20-minute intervals and at the time of seizures. The average duration of lidocaine administration required to induce seizures in the L group was 70.0 +/- 7.5 minutes, and in the TL group 29.0 +/- 7.0 minutes (P less than .05). In addition, the average serum lidocaine level at the time of seizures was 11.2 +/- 1.0 micrograms/mL in the L group and 6.2 +/- 1.7 micrograms/mL in the TL group (P less than .05). Our results show that in animals the presence of a therapeutic serum level of tocainide lowers the seizure threshold following the administration of lidocaine. These findings may have important implications for clinical care because they suggest that lidocaine should be used cautiously and in reduced dosage in patients already taking tocainide. PMID- 3109285 TI - [Physiopathological approach to pathological hyperlactatemia in the diabetic patient. Value of blood metformin]. AB - Type B lactic acidosis, or pathological hyperlactatemia (PHL), is defined by an arterial lactate level greater than 5 mmol X l-1. It is a known and severe complication of diabetes mellitus treated with biguanide hypoglycaemic agents, particularly phenformin which was taken off the French pharmaceutical market in 1977. Metformin, which remains the only biguanide hypoglycaemic agent currently prescribed in France, may also lead to this complication. However it does so less frequently and mostly in the diabetic presenting with renal failure. A few well studied cases showed that PHL could be correlated with excessive metformin blood levels, i.e. a toxic mechanism. In order to find out whether this toxic mechanism was the real cause of PHL in diabetics treated with metformin, a systematic study of metformin blood levels was carried out in 20 such patients. They had all been admitted to a critical care unit presenting with PHL. The results of this study led us to distinguish between two groups of patients. The seven patients of the first group had high metformin blood levels (4.3 to 65.8 micrograms X l-1). In these, renal excretion or extrarenal dialysis lowered or normalized their hyperlactatemia, and six of the seven recovered from PHL. In the second group, with thirteen patients, metformin blood levels were within the normal therapeutic range (0.225 to 3 micrograms X l-1) for seven patients and close to zero for the other six. This second group received the same treatment as the first one. Only three patients recovered, the others all died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109288 TI - Antigenic characteristics of enterotoxigenic and nonenterotoxigenic isolates of Bacteroides fragilis. AB - Fecal isolates of enterotoxigenic (44 isolates) and nonenterotoxigenic (25 isolates) Bacteroides fragilis were obtained from diarrheic calves (62 isolates), lambs (2 isolates), and pigs (5 isolates). Using a Microtiter whole-cell agglutination test and gel double-diffusion analysis, the isolates were reacted with nonabsorbed rabbit antisera prepared against 13 isolates of enterotoxigenic B fragilis (ETBF). Isolates of B fragilis were antigenically diverse. Thirty seven (84%) of the 44 isolates of ETBF comprised 13 serogroups on the basis of reaction in the agglutination test. Fourteen (56%) of the 25 isolates of non-ETBF comprised 4 of the 13 groups. Compared with results of the gel-diffusion test, most isolates had a different agglutination test reaction pattern against the 13 antisera. Isolates of ETBF could not be distinguished from non-ETBF. Antigenic heterogeneity of B fragilis facilitated differentiation of individual isolates, a capability that may be useful in future epidemiologic and virulence studies. PMID- 3109287 TI - Serum triiodothyronine and thyroxine concentrations in weanling horses fed carbohydrate by direct gastric infusion. AB - Plasma glucose and serum insulin, thyroxine, and triiodothyronine concentrations were monitored in 6 weanling Thoroughbreds after direct gastric infusion of solutions containing sucrose or casein. Neither plasma glucose nor serum hormone concentrations were affected by infusions of water or by infusions of 326 or 424 g of casein/250 kg of body weight. However, glucose and hormone concentrations increased significantly (P less than 0.001) after infusions of 649 or 844 g of sucrose/250 kg. Initial rates of increase were more rapid and increases were subsequently reversed more rapidly when 844 g of sucrose/250 kg was infused than when 649 g of sucrose/250 kg was infused. Soluble carbohydrate in the digestive tract triggered specific responses in the serum thyroid hormone concentrations of weanling horses. Magnitudes and durations of these responses appeared to depend on the amount of carbohydrate present. PMID- 3109289 TI - Relationship of fetal age at conjunctival exposure of pregnant heifers and Brucella abortus isolation. AB - Pregnant heifers were exposed by a conjunctival inoculation with 1 X 10(7) colony forming units of Brucella abortus strain 2308. At parturition, milk and uterine samples from dams plus samples from dead calves were cultured bacteriologically for Brucella. The logistic regression probability of B abortus isolation increased from 0.22 to 0.90, as fetal age at exposure of heifers increased from 60 to 150 gestation days. Strain 2308 was recovered at parturition from 14 (64%) of 22, 17 (71%) of 24, and all 28 (100%) heifers that were at gestation days less than 127, 127 to 157, and greater than 157, respectively, at time of exposure. The number of infected heifers and the number of samples positive for B abortus were significantly increased as fetal age at exposure of heifers increased from gestation days less than 127 to greater than 157 (chi 2 greater than 10, P less than 0.005). PMID- 3109290 TI - Pulmonary clearance of Pseudomonas aeruginosa in neutropenic mice. Effects of systemic immunization. AB - Systemic immunization with killed Pseudomonas improves pulmonary clearance of these bacteria in normal mice. To test the effects of active systemic immunization on early pulmonary clearance of Pseudomonas in neutropenic mice, Balb/c mice were intraperitoneally immunized with 10(8) Pseudomonas or injected with saline twice weekly for 2 wk. Ten days after the last immunization, immunized and control mice received tail vein injections with either nitrogen mustard or saline daily for 3 days. Two days after the last nitrogen mustard injection, mice were intrabronchially challenged with 10(6) or 10(4) live Pseudomonas and clearance was assessed 4 h later. With the higher inoculum, immunization (neutrophil-replete and neutropenic mice) augmented pulmonary clearance. The improvement in clearance with the higher inoculum was associated with a marked increase in bronchoalveolar lavage anti-Pseudomonas IgG. However, bacteria grew in the lungs of all neutropenic mice. Immunization did not alter pulmonary clearance of the lower inoculum of Pseudomonas, and bacterial growth occurred in the neutropenic mice. Gentamicin was administered to mice 2 h after intrabronchial challenge with 10(6) Pseudomonas to determine whether its effects were additive to immunization. Gentamicin improved pulmonary clearance effected by immunization only in the neutrophil-replete mice; immunization provided no additional benefit to gentamicin in the neutropenic mice. These data show that both neutrophils and immunization contribute to Pseudomonas clearance. Immunization improves pulmonary clearance of Pseudomonas in neutropenic mice with a sufficiently high inoculum, but bacterial growth still occurs. Gentamicin treatment is effective in eliminating bacteria in this model and immunization has no additional benefit. PMID- 3109291 TI - Drug-resistant tuberculosis in a southern California hospital. Trends from 1969 to 1984. AB - Resistance to one or more antituberculosis drugs was found in 98 of 281 (35%) patients hospitalized at Harbor-UCLA with culture-positive tuberculosis between 1980 and 1984. Resistance to antituberculosis drugs occurred in 23% of patients who had not been previously treated, whereas previously treated patients had a 59% rate of resistance. The overall rates of drug resistance had not significantly changed from prior studies at this hospital. Drug resistance was also found in patients with extrapulmonary disease, but tended to be less frequent than in patients with pulmonary disease. An analysis of risk factors for drug resistance rates revealed no significant differences between Hispanics, blacks, Caucasians, and Asians. Age was not found to be a significant factor to predict resistance rates. Resistance rates were higher if cavitary disease was present on radiographs. Furthermore, cavitary disease seems to be additive to prior antituberculosis treatment as a risk factor for drug resistance. Patients who had both of these risk factors present had 71% incidence of drug resistance rates. PMID- 3109292 TI - Inner-city survey for tuberculosis: evaluation of diagnostic methods. AB - A total of 1,271 persons living in a socially and economically depressed, inner city area of Vancouver, British Columbia, voluntarily attended a tuberculosis case-finding campaign. Chest x-ray, on-the-spot specimen of sputum, and tuberculin skin test were offered at the time of the first attendance. All 3 diagnostic methods were found to be well accepted, with 93% of the participants having an x-ray, over 95% producing a sputum specimen, and almost 95% having a tuberculin test (a quarter of these did not, however, report for reading of the test). Eight cases of bacteriologically confirmed pulmonary tuberculosis were found: 6 suspected on x-ray (the remaining 2 films were abnormal but not diagnostic of tuberculosis), and 6 being positive on smear and/or culture of the initial on-the-spot sputum specimen. Examination of a second specimen of sputum diagnosed all of the 8 active cases identified by the survey. These results suggest that, in this particular setting, a chest radiogram taken by a transportable chest x-ray apparatus or examination of 2 sputum specimens might be equally successful at detecting all cases of active pulmonary tuberculosis within the time required for sputum culture. Examination of the sputum smear immediately identifies all the more infectious cases of pulmonary tuberculosis. The prevalence rate of 629 per 100,000 among those presenting themselves to this campaign illustrates the high-yield which might be achieved by active case finding projects in known high-incidence segments of a generally low-incidence population. PMID- 3109293 TI - Release of vasoactive substances from guinea pig isolated lungs perfused via the trachea. AB - These findings suggest that a given stimulus, when delivered via the pulmonary circulation of a guinea pig isolated lung, does not reach a population of cells that participate in the anaphylactic response. It is likely that the endothelium in the guinea pig isolated lung acts as a barrier to stimuli coming from the circulation. This may have important therapeutic implications, particularly in regards to the respective efficacy of pharmacologic agents administered systemically or by inhalation in patients with lung injury. PMID- 3109294 TI - The importance of lipoxygenase products of arachidonic acid in allergen-induced late responses. PMID- 3109295 TI - Mast cell involvement in various inflammatory processes. AB - Mast cells from different tissue sites may have different histochemical, chemical, and functional properties. Whatever the basis for these differences, they must be important in terms of their biologic significance. Through their mediators, mast cells are involved in many different acute and chronic inflammatory processes. They act in delayed hypersensitivity, immediate hypersensitivity, and in granulomatous reactions. They can influence phagocytosis, chemokinesis, and many aspects of immune activity in several different T and B cell pathways, to mention only a few effects. Mast cells are involved in repair processes including fibroblast function and fibrosis. Their growth may be influenced by T cell-derived factors as well as factors derived from the epithelium. They appear to be intimately involved with nerves and can form apparent communications with neurones, especially those containing Substance P, which causes all types of mast cells to degranulate. Mast cells may therefore act as central switchboards between the central nervous system and migrating and sessile cell types in inflammatory processes. PMID- 3109296 TI - Altered therapeutic range for quinidine after myocardial infarction and cardiac surgery. AB - Although most assays for measuring drug levels in serum determine the total concentration, effects from a drug are determined better by measuring the concentration of unbound (free) drug in serum. When the free fraction of a drug is constant, the total drug concentration may act as a good guide in predicting drug activity. However, if the free fraction is altered from normal, the serum concentration of the total drug may be misinterpreted. Quinidine has a high binding affinity for alpha-1-acid glycoprotein. We present the case of a woman who had a myocardial infarction; after cardiac surgery, she was found to have high concentrations of alpha-1-acid glycoprotein (228 mg/dL) and a low free fraction of quinidine (0.032). At that time the patient had a total concentration of quinidine of 33.9 mumol/L (11 micrograms/mL) but showed no signs or symptoms of toxicity because the concentration of free quinidine was not high. Physicians should be aware of the limitations of assays in determining the unbound concentration of drugs in serum. This awareness is particularly crucial with drugs that bind well to serum proteins, especially when pathologic conditions change the extent of binding. PMID- 3109297 TI - Microsporidan hepatitis in the acquired immunodeficiency syndrome. PMID- 3109298 TI - Health economics: an introduction for clinicians. AB - Economic issues have had a growing importance in the health care field as the sector's share of the gross national product has risen. Clinicians are under increasing pressure to adopt more cost-effective treatment practices as a result of initiatives being taken by the major third-party payers, government, and business. However, recent publications suggest that there are some misconceptions about economics in health care and the extent to which it is in conflict with good clinical practice. To provide a foundation for the understanding of this field by clinicians, we have outlined several basic notions of health economics. PMID- 3109299 TI - [Totally implantable venous-access systems: apropos of experiences of 30 patients]. AB - Thirty-one totally implantable venous access system were investigated in patients who required intravenous administration of chemotherapy, drugs, nutrients solutions, blood products and blood sampling. Mean duration of venous access was 179 days (ranged from 9 to 429 days). Eight complications were observed, five benign without consequence on port system use, three severe (infections) requiring its removal. No death occurred during implantation and port system use. Patient acceptance was better than with other methods for repeated vascular access. In patients requiring prolonged chemotherapy, totally implantable venous access systems represent a new technique of long term venous access, with easy implantation and lack of restriction of daily activities. Review of literature show that complications are most frequently local and easy to manage. Four types of complications may have severe consequences for patient and/or port system use: catheter occlusion, venous thrombosis, local and/or general infection, and skin necrosis subsequent or not to extravasation. They represent the major cause of port system removal, but this is seldom necessary. Acquired experience allow to justify an earlier implantation of totally implantable venous access systems before chemotherapy and destruction of available surface vessels. PMID- 3109300 TI - Movements of vesicles on microtubules. AB - Many cytoplasmic vesicles are observed to move along microtubules. Often, bidirectional movement of particles is observed on a single microtubule. We have isolated one cytoplasmic motor, kinesin, and defined another, the axoplasmic retrograde factor, which are capable of powering anionic latex beads toward the plus and minus ends of microtubules, respectively. Observations of vesicle movements show that vesicles have a defined direction of movement and that vesicles copurify with a kinesin motor activity. Current evidence suggests the hypothesis that kinesin and the retrograde motors power vesicle movements in vivo by attachment to the appropriate vesicle. PMID- 3109301 TI - Regulated secretory pathways of neurons and their relation to the regulated secretory pathway of endocrine cells. PMID- 3109302 TI - Exocytosis from the vesicle viewpoint: an overview. PMID- 3109303 TI - Nevus of Ota associated with neurofibromatosis. AB - An association of neurofibromatosis with nevus of Ota is described in a young woman. The association of these disorders demonstrates a true proliferative process of neuroectodermal tissue. PMID- 3109305 TI - [Transplantar fixation in complex and unstable bi-malleolar fractures. Apropos of 23 cases]. PMID- 3109304 TI - Temporal bone collections in Europe and the United States. Observations on a productive laboratory, pathologic findings of clinical relevance, and recommendations. PMID- 3109306 TI - High volume cardioplegia. PMID- 3109308 TI - Purple urine bag syndrome. AB - Purple pigment extracted from the urinary catheters and collecting bags of two elderly female patients was analysed by a variety of chemical techniques, including mass spectroscopy and nuclear magnetic resonance. Although previous studies identified the pigment as indigo, we failed to confirm this. Our analysis also demonstrated that indicanuria is not a requirement for the production of the pigment and furthermore indicates that the molecular structure of the pigment is either a steroidal or bile acid conjugate. PMID- 3109307 TI - Bacterial contamination of QC specimens as a cause of artefactually poor performance in the UK EQAS. AB - During 1984-85, users of a solid-phase radioimmunoassay kit for LH and FSH had problems of both variability and bias in the assay of some EQAS specimens despite adequate internal QC. The cause has been identified as contamination of these specimens with Pseudomonas fluorescens. PMID- 3109309 TI - Prenatal diagnosis of non-ketotic hyperglycinaemia:amniotic fluid glycine and glycine:serine ratios. PMID- 3109310 TI - Effect of temperature on blood gas quality control materials. PMID- 3109311 TI - Effect of dietary methionine, arginine and ornithine on the metabolism and accumulation of polyamines, S-adenosylmethionine and macromolecules in rat liver and skeletal muscle. AB - The interrelationship and possible causality of polyamine synthesis and the transmethylation pathway in the growth-retarding effects of inadequate or excess dietary methionine was studied in young male rats. Feeding the rats for 2 weeks diets containing toxic concentrations of methionine had no effect on polyamine and S-adenosylmethionine metabolism in skeletal muscle, but resulted in markedly elevated concentrations of S-adenosylmethionine and S-adenosylhomocysteine and slightly decreased accumulation of spermine and RNA in the liver. These changes were accompanied by liver-specific stimulation of methionine adenosyltransferase and reduction of spermine synthase activities. Inadequate arginine feeding or supplementation of the diets with ornithine or excess arginine resulted in no apparent changes in tissue methionine or polyamine metabolism and did not alleviate the effects of varied dietary methionine supply. Inhibition of putrescine synthesis by supplementing the diets with 2-difluoromethylornithine did not modify the effects of toxic concentrations of dietary methionine. It is suggested that although hepatic spermine synthase is sensitive to excess methionine feeding, methionine toxicity is not mediated by defective polyamine metabolism. PMID- 3109312 TI - Effects in rats of dietary protein inadequacy on lactose production, milk volume and components of the lactose synthetase complex (EC 2.4.1.22). AB - Lactose synthetase (LS) is a complex of alpha-lactalbumin and N-acetylglucosamine galactosyl transferase (GT). LS is the rate-limiting enzyme in lactose biosynthesis. Lactose is the main osmotic component of milk and may thereby affect milk volume. Dietary protein inadequacy reduces milk volume and lactose content. The study investigates the role of LS activity in these phenomena. Lactating rats were fed adequate and inadequate amounts of protein of high (milk protein) and low (cereal protein) quality. After 14 days LS and GT activity of mammary tissue was measured. Milk volume and lactose content was determined. While GT activity was unaffected by diet, LS activity was reduced by low dietary protein quality. Addition of bovine alpha-lactalbumin to tissue incubates largely restored the reduced LS activities. Milk volume was affected in a parallel manner to LS activity. A highly significant positive correlation existed between LS activity and total lactose production (r = 0.794; p less than 0.001). Dietary protein inadequacy indirectly reduces milk volume by means of a direct effect on the lactalbumin part of the LS complex and, subsequently, lactose biosynthesis. PMID- 3109313 TI - Enhanced chemotherapeutic efficacy on carcinomatous peritonitis using a new dosage form in animal experiments. AB - A new dosage form, comprising Mitomycin C adsorbed on activated carbon particles (MMC-CH) was studied for its local therapeutic effects on carcinomatous peritonitis. After intraperitoneal transplantation of 10(7) cells of Yoshida sarcoma, drug treatment was given on day 2. The ED50 value on ascites was determined with Litchfield-Wilcoxon's method on day 6. The therapeutic index (LD50/ED50) on ascites in MMC-CH treatment was 3.09 times higher than that in Mitomycin C solution treatment. PMID- 3109314 TI - Tumour pH under induced hyperglycemia and efficacy of chemotherapy. AB - Blood glucose and insulin content, as well as tumour pH, were evaluated under induced hyperglycemia in Wistar or strain IOP rats bearing Guerin carcinoma. The average tumour pH decreased to 5.2-5.4, and could be maintained at this level for at least 24 hr. It was demonstrated that the antitumour effect of thiophosphamide was greatly enhanced under conditions of low tumour pH. The length of survival of rats bearing a Guerin carcinoma increased 6-fold when thiophosphamide was injected during the induced hyperglycemia. PMID- 3109315 TI - Increased survival of CD1 mice bearing dimethylhydrazine induced primary colon and anal cancers by difluoromethylornithine with concomitant increase in angiosarcoma incidence. AB - Sixty CDl mice received dimethylhydrazine 20 mg/kg s.c. once weekly for 26 weeks to induce colorectal cancer. At this time the animals harbored frank colorectal cancer and early epidermoid cancer. The animals were divided into six groups that were subjected to the following treatments: none, MTP immunotherapy (MTP) alone, radiotherapy (R) alone, difluoromethylornithine (DFMO) chemotherapy alone and combinations of R+DFMO and R+DFMO+MTP. Criteria of evaluation of treatment efficacy were: number of colorectal tumor lesion and their staging at death, the incidence and size of anal cancer at death and survival time. Radiotherapy alone was marginally effective and MTP treatment was moderately effective in preventing anal cancer and reducing the number of colorectal tumors as well as their size. DFMO was exceptional in preventing anal cancer in a majority of animals and increasing animal survival; the latter effect was due to its preventive action against pyelonephritis, the major cause for animal death. However, in DFMO treated animals, the incidence of angiosarcoma increased from 10-16% (in the absence of DFMO) to 35-50% (in the presence of DFMO). The most effective treatment of the colorectal tumor was the triple combination of R + DFMO + MTP. PMID- 3109316 TI - Altered metabolic properties of cultured skin fibroblasts in Alzheimer's disease. AB - Alzheimer's disease is associated with selective neuronal loss, the cause of which is undetermined. Evidence indicating a predisposing genetic factor associated with this disease suggests that important alterations may be expressed in tissues other than the brain. Because abnormal glucose and energy-related metabolism have been identified in both in vivo and in vitro studies of brain, we conducted a study to examine related measures in cultured skin fibroblasts from six patients with Alzheimer's disease and seven age-matched controls. After 60 minutes' incubation, the production of 14CO2 from [U-14C]glucose and lactate production were significantly higher in the cells from the group of patients with Alzheimer's disease. The increase of 14CO2 production, but not the production of lactate, was most evident after a more rapid period of metabolic activity in the first 10 minutes of incubation. By contrast, 14CO2 production from [U 14C]glutamine, which is probably the major substrate of oxidative metabolism in these cells, was significantly reduced in the Alzheimer's disease cells following longer (120-minute) incubations. Oxygen uptake by cell suspensions was also significantly reduced in the group with Alzheimer's disease. These results indicate that complex metabolic differences are expressed in nonneural tissues from some patients with Alzheimer's disease and may provide important clues to the pathogenesis of this disorder. PMID- 3109317 TI - Effect of generalized spike-and-wave discharge on glucose metabolism measured by positron emission tomography. AB - Positron emission tomography was used to study the cerebral metabolic rate for glucose (CMRGlc) in 7 adult patients with generalized spike-and-wave activity in the electroencephalogram. No consistent changes were seen in the CMRGlc. There was a slight trend toward an increased CMRGlc in 2 patients with primary generalized epilepsy, while in the 5 other patients with minor deviations from this condition or with secondary generalized epilepsy, the CMRGlc was unaffected by spike-and-wave activity or was below the normal range. Neither the amount of spike-and-wave activity in the EEG nor the presence of clinically evident absence seizures appeared to influence the CMRGlc. Therefore, we conclude that neuronal activity underlying spike-and-wave discharge does not seem to require increased glucose utilization. PMID- 3109318 TI - Percutaneous endoscopic gastrostomy. An alternative to laparotomy. PMID- 3109319 TI - Surgery on the hemophiliac patient. Special considerations. AB - Optimum care of patients with hemophilia requires cooperation among the hematologist, the surgeon, nurses, and blood bank personnel. Relatively normal hemostasis can be achieved and maintained in factor-deficient individuals in the perioperative period. Surgical procedures in patients with hemophilia can be accomplished safely with careful monitoring of coagulation factor levels and appropriate replacement therapy. PMID- 3109320 TI - A novel immobilized-enzyme system utilizing microcapsules. AB - A novel immobilized-enzyme system that has glucoamylase on the surface of, and glucose oxidase within, polyurea microcapsules was developed. This system was found to carry out its sequential enzymatic reaction effectively. It was also demonstrated that the use of microcapsules was useful for this immobilized-enzyme system since a large amount of the second enzyme, glucose oxidase, was required for the sequential reaction to proceed efficiently. In addition, this system was found helpful for making the size of reaction batches smaller. PMID- 3109321 TI - Isolation and characterization of multiple forms of prunasin hydrolase from black cherry (Prunus serotina Ehrh.) seeds. AB - Three forms of prunasin hydrolase (PH I, PH IIa, and PH IIb), which catalyze the hydrolysis of (R)-prunasin to mandelonitrile and D-glucose, have been purified from homogenates of mature black cherry (Prunus serotina Ehrh.) seeds. Hydroxyapatite chromatography completely resolved PH I from PH IIa and PH IIb. PH IIa and IIb, which coeluted on hydroxyapatite, were resolved by gel filtration. PH IIa was a dimer with a native molecular weight of 140,000. Both PH I and PH IIb were monomeric with molecular weights of 68,000. The isozymes appeared to be glycoproteins based on their binding to concanavalin A-Sepharose 4B with subsequent elution by alpha-methyl-D-glucoside. When presented several potential glycosidic substrates, these enzymes exhibited a narrow specificity towards (R) prunasin. Km values for (R)-prunasin for PH I, PH IIa, and PH IIb were 1.73, 2.3, and 1.35 mM, respectively. PH I and PH IIb possessed fivefold greater Vmax/Km values than PH IIa. Ortho- and para-nitrophenyl-beta-D-glucosides were hydrolyzed at the same active site. All forms had a pH optimum of 5.0 in citrate-phosphate buffer. PH I and PH IIb were competitively inhibited by castanospermine with Ki values of 0.19 and 0.09 mM, respectively. PH activity was not stimulated by any metal ion tested and was unaffected by diethyldithiocarbamate, o-phenanthroline, 2,2'-dipyridyl, and EDTA. PMID- 3109322 TI - Purification and characterization of dihydrofolate reductase from soybean seedlings. AB - Dihydrofolate reductase (DHFR; EC 1.5.1.3) was purified to homogeneity from soybean seedlings by affinity chromatography on methotrexate-aminohexyl Sepharose, gel filtration on Ultrogel AcA-54, and Blue Sepharose chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the enzyme gave a single protein band corresponding to a molecular weight of 22,000. The enzyme is not a 140,000 Da heteropolymer as reported by others. Amino acid sequence specific antibodies to intact human DHFR and also antibodies to CNBr-generated fragments of human DHFR bound to the plant enzyme on Western blots and cross reacted significantly in immunoassays, indicating the presence of sequence homology between the two enzymes. The plant and human enzymes migrated similarly on nondenaturing polyacrylamide electrophoretic gels as monitored by activity staining with a tetrazolium dye. The specific activity of the plant enzyme was 15 units/mg protein, with a pH optimum of 7.4. Km values of the enzyme for dihydrofolate and NADPH were 17 and 30 microM, respectively. Unlike other eukaryotic enzymes, the plant enzyme showed no activation with organic mercurials and was inhibited by urea and KCl. The affinity of the enzyme for folate was relatively low (I50 = 130 microM) while methotrexate bound very tightly (KD less than 10(-10) M). Binding of pyrimethamine to the plant enzyme was weaker, while trimethoprim binding was stronger than to vertebrate DHFR. Trimetrexate, a very potent inhibitor of the human and bacterial enzymes showed weak binding to the plant enzyme. However, certain 2,4-diaminoquinazoline derivatives were very potent inhibitors of the plant DHFR. Thus, the plant DHFR, while showing similarity to the vertebrate and bacterial enzymes in terms of molecular weight and immunological cross-reactivity, can be distinguished from them by its kinetic properties and interaction with organic mercurials, urea, KCl and several antifolates. PMID- 3109323 TI - Purification and characterization of the dog hepatic cytochrome P-450 isozyme responsible for the metabolism of 2,2',4,4',5,5'-hexachlorobiphenyl. AB - The biochemical basis for the marked difference in the rate of the hepatic metabolism of 2,2',4,4',5,5'-hexachlorobiphenyl (245-HCB) by Beagle dogs and Sprague-Dawley rats has been investigated. Control dog liver microsomes metabolize this substrate 15 times faster than control rat liver microsomes. Upon treatment with phenobarbital (PB), at least two cytochrome P-450 isozymes are induced in the dog, and the hepatic microsomal metabolism of 245-HCB is increased on both a per nanomole P-450 basis (twofold) and a per milligram protein basis (fivefold). One of the PB-induced isozymes, PBD-2, has been purified to a specific content of 17-19 nmol/mg protein and to less than 95% homogeneity, as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In a reconstituted system containing cytochrome b5, this isozyme shows an activity toward 245-HCB which is greater than threefold that seen in intact liver microsomes from PB-induced dogs. A reconstituted system containing the major isozyme induced by PB in the rat (PB-B) metabolizes 245-HCB at 1/10 the rate observed with purified PBD-2. Antibody inhibition studies have shown that PBD-2 accounts for greater than 90% of the hepatic microsomal metabolism of 245-HCB in control and PB-induced dogs, while PB-B only accounts for about half of the metabolism of this compound by microsomes obtained from PB-treated rats. Immunoblot analysis has revealed that the level of PBD-2 in dog liver microsomes increases nearly sixfold with PB treatment, and this increase correlates well with the fivefold increase in the rate of hepatic microsomal metabolism of 245 HCB by dogs. Together these data support a primary role for isozyme PBD-2 in the hepatic metabolism of 245-HCB in control and PB-induced dogs. In addition, these results suggest that, in contrast to rats, dogs can readily metabolize 245-HCB as a result of the presence of a cytochrome P-450 isozyme with efficient 245-HCB metabolizing activity. PMID- 3109324 TI - Studies on the rate-determining factor in testosterone hydroxylation by rat liver microsomal cytochrome P-450: evidence against cytochrome P-450 isozyme:isozyme interactions. AB - The aim of the present study was to examine a recent proposal that inhibitory isozyme:isozyme interactions explain why membrane-bound isozymes of rat liver microsomal cytochrome P-450 exert only a fraction of the catalytic activity they express when purified and reconstituted with saturating amounts of NADPH cytochrome P-450 reductase and optimal amounts of dilauroylphosphatidylcholine. The different pathways of testosterone hydroxylation catalyzed by cytochromes P 450a (7 alpha-hydroxylation), P-450b (16 beta-hydroxylation), and P-450c (6 beta hydroxylation) enabled possible inhibitory interactions between these isozymes to be investigated simultaneously with a single substrate. No loss of catalytic activity was observed when purified cytochromes P-450a, P-450b, or P-450c were reconstituted in binary or ternary mixtures under a variety of incubation conditions. When purified cytochromes P-450a, P-450b, and P-450c were reconstituted under conditions that mimicked a microsomal system (with respect to the absolute concentration of both the individual cytochrome P-450 isozyme and NADPH-cytochrome P-450 reductase), their catalytic activity was actually less (69 81%) than that of the microsomal isozymes. These results established that cytochromes P-450a, P-450b, and P-450c were not inhibited by each other, nor by any of the other isozymes in the liver microsomal preparation. Incorporation of purified NADPH-cytochrome P-450 reductase into liver microsomes from Aroclor 1254 induced rats stimulated the catalytic activity of cytochromes P-450a, P-450b, and P-450c. Similarly, purified cytochromes P-450a, P-450b, and P-450c expressed increased catalytic activity in a reconstituted system only when the ratio of NADPH-cytochrome P-450 reductase to cytochrome P-450 exceeded that normally found in liver microsomes. These results indicate that the inhibitory cytochrome P-450 isozyme:isozyme interactions described for warfarin hydroxylation were not observed when testosterone was the substrate. In addition to establishing that inhibitory interactions between different cytochrome P-450 isozymes is not a general phenomenon, the results of the present study support a simple mass action model for the interaction between membrane-bound or purified cytochrome P-450 and NADPH-cytochrome P-450 reductase during the hydroxylation of testosterone. PMID- 3109326 TI - [Bone metastasis from renal cell carcinoma]. AB - The subjects of this study were 38 patients with bone metastasis out of 124 cases of primary renal cell carcinoma treated at the National Cancer Center Hospital. The risk factors affecting the development of bone metastasis were considered. It is quite natural for the occurrence rate to be high in patients at an advanced stage of disease. However, from histopathological investigations of primary lesions, a tendency for bone metastasis is often observed in alveolar-type, solid (sarcomatoid)-type and mixed-type tumors as classified on the basis of histologic structure, for granular cell subtype on the basis of classification by cell type, and for grades 3 and 4 on the basis of classification by nuclear grading. Although radiation therapy and tumor artery infusion therapy were performed for metastatic bone lesions, the results obtained this time appeared to suggest no notable improvements in objective findings. PMID- 3109325 TI - [Prospectives on cancer treatment in the future--from its clinical aspects]. AB - Remarkable progress has been achieved in the treatment of gastric cancer during these three decades, the late survival rate being increased twice or more. The factors attributing to this result were analyzed and prospect for further progress was discussed. One of the most promising ways for this purpose lies in the development of multidisciplinary treatment. So far the mode of thinking has been placed on the organ-oriented basis. However, the search should be directed to the treatment specifically effective to each biological type involved in the tumor. A concept of "Type-Oriented Treatment" was proposed herein. PMID- 3109327 TI - [Comparative study of the activating effects of recombinant human interleukin 2 and interferon-gamma on cell-mediated cytotoxicity against renal cell carcinoma in vitro]. AB - The effects of recombinant interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) on lymphocyte-mediated cytotoxicity against established human renal carcinoma cell lines KU-2 and Caki 1, and freshly prepared human renal carcinoma cells were compared in vitro. After incubation of peripheral blood lymphocytes from normal adult volunteers with IL-2 and IFN-gamma over a range of concentrations, cytotoxicity was determined by 4-h 51Cr-release assay. Augmentation of cytotoxicity by IL-2 and IFN-gamma was dose-and time-dependent. IL-2 induced significantly greater cytotoxicity against renal carcinoma cells than did IFN gamma. The optimal dose of IL-2 was 100 to 500 units/ml, and cytotoxicity was increased even at concentrations as low as 4 units/ml. The results indicated that the systemic administration of IL-2 to patients will be effective for treatment of renal cell carcinoma which is resistant to interferon therapy. A continuous infusion or multiple repeated bolus doses over a period of one day, however, should be considered in order to maintain high levels of IL-2 in the serum. PMID- 3109328 TI - [Combined effect of human recombinant interferon-beta and interferon-gamma against an experimental model of peritonitis carcinomatosa in nude mice]. AB - The development of useful therapy for the peritonitis carcinomatosa of gastrointestinal cancer is an important theme in cancer therapy. We developed an experimental model of peritonitis carcinomatosa in nude mice transplanted intraperitoneally human colon cancer cells. In this study, we investigated combined effect of human recombinant interferon-beta (rIFN-beta) and recombinant interferon-gamma (rIFN-gamma) in vivo using this model. The result indicate that each rIFN-beta and rIFN-gamma showed a significant prolonged survival compared with the control group (mean survival days: 41.8 +/- 5.0 days). Furthermore, combined administration of rIFN-beta and rIFN-gamma showed a marked prolonged survival (mean survival days: 114.0 +/- 7.4 days) compared with rIFN-beta or rIFN gamma alone. These results suggest that a combined treatment of rIFN-beta and rIFN-gamma may be useful against peritonitis carcinomatosa of gastrointestinal cancer. PMID- 3109329 TI - [Side effects and anti-cancer effects following intraperitoneal (ip) administration of mitomycin C (MMC)]. AB - Nineteen patients with gynecological cancers were initially treated intraperitoneally with MMC at a dose of 20 to 52 mg/body and then intravenously with CAP regimen. The following side effects were observed in patients intraperitoneally administered doses of MMC greater than 25 mg/m2; leucocytopenia 7/12, thrombocytopenia 5/12, liver damage 8/12, renal damage 2/12, ileus 3/12 and severe anorexia 2/12. Sixteen patients were evaluated for their prognoses more than 1 year after treatment. Seven of them are well with no sign of recurrence, but 9 suffered recurrence with or without peritonitis carcinomatosa (PC). The incidence of PC among these 9 cases was not linked with clinical staging, complete or incomplete resection or the dose of MMC administered, but rather with the respective histopathology; mesonephroid 2/2, metastatic 2/2, mucinous 1/1, serous 0/3, endometrial corpus 0/1. The results suggested that the former 3 kinds of cancer did not respond to i.p. infusion of MMC, whereas the latter 2 were sufficiently sensitive to MMC to prevent the occurrence of PC. PMID- 3109331 TI - [Advanced gastric cancer with DIC and multiple bone metastasis treated with surgical resection and chemotherapy]. AB - Endoscopic examination of a 35-year-old patient complaining of tarry stool, palpitation and lumbago led to a diagnosis of gastric cancer of Borrmann type 4. Laboratory data and bone scintigraphy revealed findings of DIC and multiple bone metastasis. He was treated with continuous intravenous infusion of FOY, but laboratory data with DIC went from bad to worse. It was considered that resection of the tumor was effective for DIC, then total gastrectomy and partial transverse colonectomy were performed, and the patient recovered from DIC. For the multiple bone metastasis, he received chemotherapy using cisplatinum and mitomycin C, and subsequent bone scintigraphy showed a dramatic improvement. Doxorubicin and 5 fluorouracil controlled peritoneal dissemination of the cancer. PMID- 3109330 TI - [Improved quality of life in a patient with Borrmann type 4 gastric cancer treated with combination chemotherapy]. AB - A 49-year-old nursery school teacher noticed epigastric discomfort and loss of appetite, and was hospitalized for diagnosis and treatment on Dec. 19, 1984. She was diagnosed to have Borrmann type 4 gastric cancer with Schnitzler's metastasis. After one month's administration of UFTM-O (UFT, mitomycin C, OK-432) subjective symptoms disappeared and improvement of the gastric lesion was demonstrated 2 months later. On Apr. 4, 1985 she was able to return to work, receiving UFTM-O therapy for one year as an outpatient. When ascites appeared in October, UFTM-O was discontinued and a single intraperitoneal administration of cis-platinum was done for peritoneal effusion. Another combination chemotherapy consisting of MTX, 5-FU and OK-432 was started, but she died 3 months later. In consequence, she had been able to live 18 months from the initial diagnosis. Moreover, she was able to enjoy a high quality of life, which meant she was able to return to her work and travel abroad, during the initial two-thirds of the disease period. PMID- 3109332 TI - [Two cases of unresectable pancreatic cancer responding to combined chemotherapy with cisplatin, PSK and UFT]. AB - Two patients who had unresectable pancreatic cancer were treated with a combined chemotherapy using Cisplatin, PSK and UFT. A remarkable decrease of tumor size was observed on CT. These two cases corresponded to partial response (PR) according to the response criteria proposed by Koyama-Saitoh. No significant side effects were observed during this therapy. From the results in these two cases, this combination chemotherapy was considered to be one of the most effective antineoplastic therapies available for pancreatic cancer. PMID- 3109333 TI - [Method for analysis of the DNA content of paraffin-embedded tissue using flow cytometry-pepsin enzymatic disaggregation]. PMID- 3109334 TI - [Advances in mitomycin studies--clinical studies: progress over 10 years]. AB - Novel clinical trials with mitomycin C (MMC) have been more frequently reported in Europe and the States than in Japan. It was considered useful for the future development of clinical studies to summarize the results presented mainly in these latest reports. In this paper, clinico-pharmacological results, results by single and combined therapies, results by intraarterial infusion, researches of derivatives and trials of local chemotherapy using the drug delivery system are summarized, and reports on hemolytic-uremic syndrome, which is said to be possibly caused by MMC, are introduced briefly. Such reports have recently been published also in Japan. On the whole, it can be concluded that, though MMC has still held the place as the most extensively applicable antineoplastic agent, it cannot be used by any other methods than the middle-dose intermittent administration for preventing side effects. More detailed studies on mechanisms of its therapeutic actions and adverse effects are needed for further investigations on effective application of MMC and for finding out useful derivatives. It is desirable that these investigations will be more actively conducted in Japan. PMID- 3109336 TI - Effect of polychlorinated biphenyls (PCBs) accumulated in the dam's body on mouse filial immunocompetence. PMID- 3109337 TI - [Surgical management in the pathology of the schistosomiasis ureter]. PMID- 3109335 TI - Serum IgG antibodies in patients with cystic fibrosis with early Pseudomonas aeruginosa infection. AB - Serum IgG antibodies to Pseudomonas aeruginosa surface antigens were measured by enzyme linked immunosorbent assay in all patients with cystic fibrosis from whom P. aeruginosa was isolated for the first time during a study period of 18 months. In 15 patients the titre of serum IgG antibodies was greater than control values before or at the time of the first bacteriological isolation of P. aeruginosa. The presence of serum antibodies specific to P. aeruginosa suggests exposure to infection by that organism for some months before its isolation in significant numbers from the respiratory tract. In the other two patients serum titres were within the control range before isolation of P. aeruginosa but had increased to above the control range within the next month. Longitudinal studies on the entire group of patients showed further increases in titre concurrently with further isolations of P. aeruginosa. These results suggest that this assay may be an indicator of the beginning of pulmonary infection by P. aeruginosa and may prove to be a sensitive monitor of the progress of infection, and response to treatment, during the first months of infection by that organism. PMID- 3109338 TI - Management of tuberculous pericarditis. AB - The cases of 17 patients with tuberculous pericarditis were reviewed. Thirteen patients had effusive pericarditis, and 10 had surgical drainage of the effusion. No deaths were due to pericardial tamponade; this appears to be related to earlier recognition of major pericardial effusions by echocardiography. In 2 patients clinical evidence of pericardial constriction developed while they were on a regimen of therapy, and in another 2 patients, echocardiography revealed pericardial thickening after resolution of the effusion. A pericardial window is recommended for the short-term management of patients suspected of having tuberculous pericarditis with a major pericardial effusion by echocardiography. If a thickened pericardium is found during the window procedure, early pericardiectomy is strongly encouraged. PMID- 3109339 TI - Distant graft procurement for combined heart and lung transplantation using pulmonary artery flush and simple topical hypothermia for graft preservation. AB - Although combined heart and lung transplantation has great potential for improving survival and rehabilitation in selected patients with pulmonary vascular disease, the lack of suitable donor organs has restricted the number of operations performed. We report a heart and lung transplantation operation for Eisenmenger's syndrome in which distant donor graft procurement was used with a simple system for preservation. PMID- 3109340 TI - A multidimensional approach to the assessment of clinical validity in a study on CCVD treatment: dihydroergocristine versus placebo. AB - An example of multidimensional assessment procedure applied to the study of treatment effects in a type of pathological aging is presented in this paper. Data discussed here come from a clinical trial performed to evaluate the effects of an ergot derivate, dihydroergocristine, in CCVD memory deficits. The multidimensional assessment procedure consisted of behavioral, clinical, and psychometric measures aimed to identify both the results related to drug activity (experimental validity), and the implications that these eventual drug-induced changes have on the everyday life patients' competence (clinical validity). 97 out-patients (both sexes were represented), with a mean age of 61.21 y (SD 7.29), who suffered from mild to moderate chronic cerebro-vascular disturbances were included in this double-blind study only when they met rigid inclusion criteria. The experimental period was 12 weeks. Results indicate a pattern of convergent, statistically significant, changes which evidence how treatment-associated memory changes are accompanied by an improvement of emotional and physical well being and by a modification of behavioral structure which is characterized by greater efficiency and greater responsiveness to stimuli. PMID- 3109341 TI - Acquired hemophilia. A natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy. AB - Rarely, a patient develops an antibody against factor VIII coagulant activity. The resultant hemorrhagic diathesis is clinically distinct from inherited hemophilia, being characterized by few hemarthroses but frequent skin and other soft-tissue hematomas. Hematuria may be troublesome. These patients represent therapeutic challenges. This study is one institution's results with 16 such patients followed up over an average of 31 months (range, four to 120 months; median, 19 months). It describes the largest group from a single institution receiving essentially no immunosuppressive agents, yet has one of the better overall results. Two patients experienced fatal hemorrhage and five patients underwent spontaneous remission. Long-term survival is not incompatible with persistence of the inhibitor. We conclude that this hemorrhagic diathesis is clinically distinct, less fatal than usually perceived, and may undergo spontaneous remission. Clearly, there is no mandate for any particular therapeutic regimen, such as immunosuppression, in the attempt to rid the patient of the antibody. PMID- 3109342 TI - Presence of several molecular forms of gonadotropins in pituitary adenomas. PMID- 3109343 TI - Serum gonadotropins and 17-beta-estradiol concentrations in girls from the newborn period up to puberty. PMID- 3109344 TI - Serum proteinase levels, platelet functional and morphological alterations in patients with cervix uteri carcinoma. Correlation with the degree of progression of the malignancy. PMID- 3109345 TI - Light-adaptation in the photophobic response by Stentor coeruleus. AB - Effects of preillumination on photophobic response (light-adaptation) and recovery of the photophobic sensitivity in the dark (dark-adaptation) in Stentor coeruleus were examined. When the cells were preilluminated with white light of 7.80 W/m2 for 2 min, the fluence-rate response curve of photophobic response was shifted toward higher light intensities by half an order of magnitude compared to the one without preillumination. Preillumination with a higher light intensity resulted in a further shift of the fluence-rate response curve. An action spectrum for light-adaptation showed a primary peak at 610 nm and secondary peaks at 540 and 480 nm which are almost identical to the peaks observed in the photophobic action spectrum. The light-adapted cells showed a recovery of their photophobic sensing ability following dark treatment. Dark-adaptation resulted in total recovery of photophobic sensing ability in 8 minutes for the most cases examined. PMID- 3109346 TI - Influence of iron(III) and pyoverdine on extracellular proteinase and lipase production by Pseudomonas fluorescens B52. AB - Factors associated with the production of extracellular lipase and proteinase by Pseudomonas fluorescens B52 during the late-log, early-stationary phase of grown were examined. Active lipase production by resting cell suspensions was observed when cells were harvested during the log phase (A600 of 0.3-0.9). Resting suspensions of younger cells (A6000 less than 0.1) synthesized lipase after a significant lag. Addition of cells of the proteinase- and lipase-deficient mutant P. fluorescens RM14 to B52 cells at low density resulted in stimulation of lipase and proteinase production. Similar results were found using cell-free culture fluid of RM14. Gel filtration on Biogel P2 revealed that the stimulatory factor co-chromatographed with the iron(III) siderophore, pyoverdine. Partially purified pyoverdine stimulated enzyme synthesis at a concentration of 6 microM while having no effect on activity of preformed enzyme. Production of pyoverdine and extracellular enzymes was also stimulated by transferrin, a strong iron(III) binding protein. Growth of B52 in deferrated media was limited to 27% of that found with untreated media. Maximum pyoverdine, proteinase and lipase synthesis was obtained at a final iron(III) concentration of 5.75 microM. Growth was maximal in 8.75 microM iron(III) while synthesis of pyoverdine, proteinase and lipase was reduced to 3.6, 6.6 and 30% respectively in 23.75 microM iron(III). Lipase activity in cell-free culture fluid was slightly inhibited by the addition of up to 400 microM iron(III) while proteinase activity was unaffected. In dilute cell suspensions, lipase synthesis was more sensitive to iron(III) than was proteinase (50% inhibition at 1.6 microM and a maximum of 40% inhibition at 5.0 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109347 TI - [Treatment of central precocious puberty with an LHRH analog. Effect on growth and bone maturation after 2 years of treatment]. AB - Eighteen children (15 girls and 3 boys) with true precocious puberty have been treated with an LHRH analogue (HOE 766, Buserelin suprefact) given subcutaneously during one (n = 11) or two (n = 7) years. Six of 18 children had organic precocious puberty, but their responses to therapy did not show any difference. A satisfactory suppression was achieved in 16 cases with plasma testosterone below 0.5 ng/ml (boys) or estradiol below 25 pg/ml and vaginal maturation index below 35 (girls). The mean annual height gain diminished from 9.5 +/- 0.8 cm during the control year to 7.7 +/- 0.7 cm and 5.1 +/- 0.7 cm during the first and second years of therapy respectively (p less than 0.05). Simultaneously, the mean bone age of 10.4 +/- 0.4 yr at onset of treatment, was 11.4 +/- 0.4 yr after one year and 11.8 +/- 0.3 yr after two years. These changes explain an average increase of predicted height of 5.7 cm after two years of treatment with the LHRH analogue. At least on the basis of these data with two years follow-up, this treatment seems satisfactory. We did not find anti-Buserelin antibodies in any of these patients. PMID- 3109348 TI - Immunomodulatory effect of Listeria monocytogenes infection. I. Allotransplantation reaction in infected mice. AB - The rejection reaction of skin graft in Listeria monocytogenes infected mice was examined in the allogeneic system: recipient Balb/c mice (haplotype H-2d) and donor G3H mice (haplotype H-2k). It was observed that this reaction was significantly potentiated when skin allograft was transplanted in the period of the highest monocytosis and the strongest delayed type hypersensitivity to Listeria monocytogenes antigen in the infected recipients. This finding suggests that the allotransplantation reaction in Listeria monocytogenes infected organism may be intensified by the activated monocyte-macrophage lineage cells cooperating with the lymphocytes sensitized to Listeria antigen. PMID- 3109349 TI - Immunomodulatory effect of Listeria monocytogenes infection. II. Natural cell cytotoxicity in infected mice. AB - The natural cell cytotoxicity of blood leukocytes, splenocytes and peritoneal cells derived from Balb/c mice being on day 1, 3, 5, 7, 9 of listeriosis to allogeneic fibroblast L 929 was examined. The intensity of cytotoxic reaction was assessed by the per cent of specific 51Cr release from target cells. To check if this reaction correlates with the level of monocyte-macrophage lineage cells present in the effector cells of if it depends on the development of delayed type hypersensitivity to Listeria antigen, Balb/c mice were infected with Listeria monocytogenes and simultaneously treated with ATS. It was found that Listeria monocytogenes infection in mice enhanced the natural cell cytotoxicity of tested effectors cells, particularly of peritoneal cells in animals being on the 5th-7th day of listeriosis. The treatment of mice with ATS which is known to inhibit the development of delayed type hypersensitivity to Listeria antigen, completely suppressed the stimulatory effect of this infection on the natural cell cytotoxicity to allogeneic fibroblasts. This finding suggests that the enhancement of natural cytotoxic activity of tested effector cells results from the action of activated macrophages cooperating with Listeria sensitized T lymphocytes. PMID- 3109350 TI - Immunological relationship among glycogen-protein complexes of different species. AB - Glycogen-protein complexes from the muscles of Celerio euphorbiae and horse as well as from the livers of frog, carp and man were isolated and used as antigens. After immunization of rabbits antisera were obtained from which fractions of immunoglobulins were isolated. Antibodies were used in agar immunodiffusion tests and in quantitative reaction of immunoprecipitation with glycogens. The immunoprecipitation test proved the occurrence of quantitative differences in cross reaction of complexes with different origin antibodies, testifying to variability of their antigen properties. The immunodiffusion test allows to suppose the presence in antigens of at least two determinants of protein carbohydratic character. PMID- 3109351 TI - Histamine binding proteins identified in healthy subjects and asthmatic patients. AB - Histamine-binding proteins have been isolated from healthy subjects and patients with endogenous bronchial asthma. Histaminopectic properties were exhibited mainly by IgA, IgG, IgM immunoglobulins, orosomucoid, albumin and ceruloplasmin. Quantitative determination of the identified proteins showed that in the control group immunoglobulins bound histamine in 97.5%, whereas in asthmatics the corresponding percentage (about 81%) was statistically significantly lower. PMID- 3109353 TI - Duodenojejunostomy for pancreatitis secondary to periampullary duodenal diverticula. PMID- 3109352 TI - Metabolic and immune effects of dietary arginine supplementation after burn. AB - The effect of supplemental dietary arginine on metabolism and immunity was studied in 36 burned guinea pigs (30% of total body surface area) with previously placed catheter gastrostomies. The animals were randomized into four groups. After an initial three-day adaptation period, all groups received continuous isonitrogenous, isocaloric (175 kcal [735 kJ]/kg/d), and isovolemic intragastric tube feedings until postburn day (PBD) 14. Groups A, B, C, and D received 0%, 1%, 2%, and 4%, respectively, of total energy intake as arginine given in the form of crystalline arginine hydrochloride with 22%, 21%, 20%, and 18%, respectively, of total energy as whey protein. The average body weight after burn decreased equally in all groups. Resting metabolic expenditure on PBD 6 was higher in groups B (151% +/- 6% of preburn) and C (156% +/- 7%) than in groups A (131% +/- 4%) and D (136% +/- 3%). Ear-thickness response to dinitrofluorobenzene challenge on PBD 12 showed the best response in group C. The mortality rates of groups A, B, C, and D were 56%, 29%, 22%, and 56%, respectively. This study suggests that oral dietary arginine supplementation up to 2% of energy intake may be beneficial after burn injury. PMID- 3109354 TI - [Arrhythmias and the indeterminate form of Chagas' disease]. PMID- 3109355 TI - [Maximal functional capacity by ergospirometry in patients with Chagas' disease]. PMID- 3109356 TI - [Critical analysis of the indeterminate form of Chagas' disease]. PMID- 3109357 TI - Barbiturate-refractory epilepsy: safe schedule for therapeutic substitution. AB - Barbiturates are considered first line antiepileptic drugs in third world countries due to traditional and economic reasons. This prospective uncontrolled study of 52 patients aged 15 to 64 years (mean 24) demonstrates that patients who become refractory to barbiturates are mainly those with partial seizures with or without generalization or with a focal EEG abnormality (71%). Seizures tend to become refractory approximately 6 years after barbiturates were started. Progressive barbiturate withdrawal over a period of two to 8 months (mean 5) with institution of treatment with carbamazepine, phenytoin or sodium valproate allowed complete barbiturate withdrawal in 42 of the 52 patients (81%). Furthermore monthly seizure frequency in those in whom barbiturates were withdrawn decreased from 7.1 to 1.7 per patient. An improvement in mental status was observed but not measured. These results show that barbiturates should not be first-choice drugs in patients who have a chronic disease such as epilepsy, and indicate a schedule for barbiturate withdrawal which is safe and independent of hospitalization or monitoring of antiepileptic drug serum concentrations. PMID- 3109358 TI - [Neuroschistosomiasis]. AB - The low incidence of mansoni schistosomiasis involving the nervous system calls our attention in a country where 12 million people carry the intestinal form of the disease. Also, during autopsies the incidence of the parasites eggs occurs three to four times more often than the cases diagnosed in life. Therefore, new investigations become necessary around endemic areas. The cerebrospinal fluid syndrome of the neuroschistosomiasis must be searched among patients from endemic areas who present neurological symptoms and which cause is unknown. The probable protein liberation giving signs in the CSF and causing the demyelinization or the axonal degeneration at a distance is emphasized among the physiopathological factors. Two cases of neuroradiculomyelitis with positive copro analysis and CSF syndrome for mansoni schistosomiasis are presented and discussed; both were treated with success using praziquantel in association with steroids for a period of fourteen days. PMID- 3109359 TI - Lupus anticoagulant and stroke. PMID- 3109360 TI - Valproic acid loading during intensive monitoring. AB - Of 35 patients who had generalized tonic-clonic seizures during antiepileptic drug therapy withdrawal, "loading" with valproic acid was effective in limiting these seizures in 32 patients. A loading dose of approximately 12.5 mg/kg was used. This dose resulted in valproic acid levels between 284 and 458 mumol/L (41 and 66 mg/L) 1.5 hours after "loading" in six of the eight patients in whom serum concentrations were measured. PMID- 3109361 TI - Ovarian stimulation for disordered ovulatory cycles. PMID- 3109362 TI - Antibiotic advice. PMID- 3109363 TI - Accumulation of chlorpromazine and thiouracil by human melanoma cells in culture. AB - The uptake (total radioactivity in intact cells) and incorporation (radioactivity bound to acid-precipitable material) of 14C-chlorpromazine (CPZ) and 14C thiouracil (TU) were studied using a library of 3 human fibroblast strains and 13 tumour cell lines. In contrast to previous studies using rodent melanomas in vivo, the melanoma lines, including lines with high tyrosinase and melanin contents, did not take up more CPZ and TU than non-melanoma cells (fibroblasts, HeLa cells). Incorporation of CPZ was also broadly similar in all cell types studied. TU was selectively incorporated into the melanoma line having a high tyrosinase and melanin content but not into lines with high tyrosinase activity and low melanin content. While supporting the possibility of selective therapy for heavily-pigmented melanomas using labelled TU derivatives, these results suggest that the action of potentially melanoma-affined compounds should be further evaluated in human cells. Unlabelled CPZ or TU was not selectively toxic to melanoma cells. Unexpectedly, methylation-sensitive tumour cells (Mer phenotype) were highly resistant to TU, thus providing a new experimental tool for understanding the genesis of this phenotype in vivo. PMID- 3109365 TI - Pulsatility of reproductive hormones: applications to the understanding of puberty and to the treatment of infertility. PMID- 3109364 TI - Oestrogen replacement therapy: physiological considerations and new applications. AB - The total impact of the menopause on the health of women and the ultimate benefit/risk ratio of oestrogen replacement therapy are yet to be defined completely. Until these are accomplished, broad general guidelines for the use of oestrogen replacement therapy in all patients cannot be given. Treatment should be individualized to the patient's specific needs. Use of appropriate dosages of oestrogen in combination with progestin administration should reduce risk and enhance benefits for those subjects requiring its use. The development of new non oral methods of administration should also help. PMID- 3109366 TI - Clinical applications of LHRH analogues. AB - What is the current state of clinical application of inhibition of gonadal activity with LHRH agonists or antagonists? It seems unlikely in the short term that antagonists will be widely applied due to the short-acting nature of the present compounds and their troublesome side-effects. In contrast clinical studies with a number of agonists have demonstrated their efficacy in producing a hypogonadal state safely with rapid recovery following cessation of therapy. Although nasal administration may be suitable for short-term suppression (up to 28 days) it seems likely that long-acting depot preparations will be useful for more prolonged suppression. Perhaps the easiest application to determine will be the profound suppression required to produce medical castration in hormone dependent tumours. The combination of agonist and receptor blocker is attractive particularly when the receptor blocker like cyproterone acetate also suppresses the release of LH, FSH and adrenocorticotrophic hormone. In cancer of the prostate and breast the side-effects due to inhibition of secretion of testosterone and oestradiol are tolerable although the only benefit over castration is the avoidance of minor surgery. The agonists should improve significantly the existing treatment for precocious puberty, endometriosis, uterine fibroids, polycystic ovary syndrome (PCO) and induction of ovulation although large scale trials comparing different therapies and doses are required. Finally, the concept of combination therapies to block further the influence of steroid hormones suggests challenging possibilities for even more effective therapy. PMID- 3109367 TI - Endocrinology of the hypothalamic-pituitary-testicular axis with particular reference to the hormonal control of spermatogenesis. AB - The normal physiology of the hypothalamic-pituitary-testicular axis in man is reviewed. According to current concepts, LH plays an important role in the initiation and maintenance of spermatogenesis by stimulating Leydig cell production of high concentrations of T within the testes. FSH is thought to be important in spermatid maturation (spermiogenesis) during the initiation of spermatogenesis by stimulation of Sertoli cells. Studies of selective gonadotrophin replacement in experimentally-induced hypogonadotrophic hypogonadal men demonstrate that qualitatively normal sperm production can be achieved by replacement of either LH or FSH alone, but both LH and FSH are necessary to maintain quantitatively normal spermatogenesis. Studies of gonadotrophin replacement in spontaneously-occurring hypogonadotrophic men suggest that the requirement for FSH activity to stimulate sperm production is greatest during the initiation of sperm production at the time of puberty. The initiation of spermatogenesis in postpubertal men with acquired hypogonadotrophic hypogonadism and the maintenance of spermatogenesis after its initiation can often be achieved with LH activity alone. PMID- 3109368 TI - Inhibin--a non-steroidal regulator of pituitary follicle stimulating hormone. AB - Inhibin is a gonadal glycoprotein produced by the granulosa and Sertoli cell under the influence of FSH and acts to specifically suppress pituitary FSH secretion. Recently, ovarian inhibin has been purified from several species and its amino acid sequence deduced using cloning techniques. Inhibin consists of two disulphide-linked heterologous subunits of which the smaller may exist in two different forms accounting for two different forms of inhibin in humans and pigs. Heterogeneity of inhibin also exists as a result of proteolytic processing of the molecule during its passage into the circulation. Significant homology exists between the subunits of inhibin and the dimeric peptides TGF-beta and Mullerian inhibitory substance (MIS), suggesting they are all derived from a common ancestral gene. Furthermore, dimers of the smaller subunit of inhibin (FSH releasing protein (FRP) or activin) have now been found in follicular fluid (FF) and, along with TGF-beta, shown to be potent and specific stimulators of FSH secretion. These proteins may be involved in controlling FSH by another as yet unknown pathway and may prove to be the FSH-releasing factor, analogous to LHRH, which has been postulated to exist for some years. Inhibin can no longer be simply considered as an isolated FSH-suppressing protein. The physiological significance and relationship between inhibin and its related proteins represent one of the most challenging and interesting areas in reproductive endocrinology. Further studies, particularly with the development and use of sensitive assays for both the FSH releasing hormone and inhibin will clarify their role in reproduction and their usefulness in monitoring or treating fertility. PMID- 3109369 TI - Circadian and ultradian rhythms in period mutants of Drosophila melanogaster. PMID- 3109370 TI - The ontogeny of sex appeal in Drosophila melanogaster males. PMID- 3109371 TI - Visual assays of transformation in plant cells. AB - We discuss the utility of visual assays for the expression of genes introduced into plant cells. Such assays are valuable for both transient and stable gene expression studies. We review the properties of three visual assays that are already in use or under development phase for maize and other cereal crops. These assays depend on the expression of beta-galactosidase, luciferase, or structural genes required for anthocyanin pigment biosynthesis. PMID- 3109372 TI - [Diffuse neurofibroma of the palm--a case report]. PMID- 3109373 TI - The stimulatory guanine-nucleotide regulatory unit of adenylate cyclase from bovine cerebral cortex. ADP-ribosylation and purification. AB - Hormonal stimulation of adenylate cyclase from bovine cerebral cortex is mediated by a guanine-nucleotide regulatory protein (Gs). This protein contains at least three polypeptides: a guanine nucleotide-binding alpha s component and a beta X gamma component, which modulates the function of alpha s. The alpha s component from many tissues can be ADP-ribosylated with cholera toxin, but has been unusually difficult to modify in brain. We have improved incorporation of ADP ribose by including isonicotinic acid hydrazide to inhibit the potent NAD glycohydrolase activity of brain. ADP-ribosylation is further improved by addition of detergent to render the substrates accessible and 20 mM-EDTA to chelate metal ions. Although Mg2+ is absolutely required for activation of adenylate cyclase by the GTP analogue guanosine 5'-[beta gamma-imido]triphosphate (p[NH]ppG), it is not obligatory for p[NH]ppG-stimulated ADP-ribosylation by cholera toxin. Under these conditions, the ADP-ribosylation of brain membranes is not enhanced by a cytosolic protein. We find that there are two major sizes of brain alpha s, which we have named 'alpha sL', with an apparent Mr of 42,000 45,000, and 'alpha sH' with an apparent Mr of 46,000-51,000 depending on the gel electrophoretic system used. The alpha sL and alpha sH components can incorporate different amounts of ADP-ribose depending on the reaction conditions, so that one or the other may appear to predominate. Thus we show that incomplete ADP ribosylation by cholera toxin is not a good indication of the relative amounts of alpha s units. Functionally, however, both forms of alpha s appear to be similar. Both forms associate with the catalytic unit of adenylate cyclase, but neither of them does so preferentially. There is an excess of each of them over the amount associated with catalytic unit. We have now substantially purified Gs from brain by a modification of the method of Sternweis et al. [(1981) J. Biol. Chem. 256, 11517-11526] as well as by a new, simplified, procedure. On SDS/polyacrylamide gel electrophoresis, the purified brain Gs contains both the 45 and 51 kDa alpha s polypeptides revealed by ADP-ribosylation and a beta X gamma component. Activation of purified alpha s by guanine nucleotides or fluoride can be reversed by addition of purified beta X gamma component. The activated form of purified brain Gs has an Mr of 49,000 as determined by hydrodynamic measurements, which is consistent with the idea that the active form of brain Gs is the dissociated one. PMID- 3109374 TI - Effect of inhibitors of arachidonic acid metabolism on efflux of intracellular enzymes from skeletal muscle following experimental damage. AB - The role of arachidonic acid metabolism in the efflux of intracellular enzymes from damaged skeletal muscle has been examined in vitro using inhibitors of cyclo oxygenase and lipoxygenase enzymes. Damage to skeletal muscle induced by either calcium ionophore A23187 (25 microM) or dinitrophenol (1 mM) caused an increase in the efflux of prostaglandins E2 and F2 alpha together with a large efflux of intracellular creatine kinase. Use of a cyclo-oxygenase inhibitor completely prevented the efflux of prostaglandins, but had no effect on creatine kinase efflux. However, several agents having the ability to inhibit lipoxygenase enzymes dramatically reduced creatine kinase efflux following damage. These data suggest that a product or products of lipoxygenase enzymes may be mediators of the changes in plasma membrane integrity which permit efflux of intracellular enzymes as a consequence of skeletal muscle damage. PMID- 3109375 TI - Biosynthesis and maturation of lactase-phlorizin hydrolase in the human small intestinal epithelial cells. AB - The biosynthesis and maturation of the human intestinal lactase-phlorizin hydrolase (LPH; EC 3.2.1.23-3.2.1.62) has been studied in cultured intestinal biopsies and mucosal explants. Short time pulse labelling revealed on high mannose intermediate of Mr 215,000 which was converted upon endo-beta-N acetylglucosaminidase H (endo-H) digestion to a polypeptide of Mr 200,000. The brush border form of LPH was revealed after longer pulse periods and has Mr 160,000. It possesses mainly complex oligosaccharide chains and, owing to its partial endo-H sensitivity, at least one chain of the high mannose type. Leupeptin partially inhibited the appearance of the Mr-160,000 polypeptide. Monensin treatment of biopsies resulted in the modification of the Mr-160,000 species to the Mr-140,000 molecule, which was endo-H sensitive. Pulse-chase analysis indicated a slow post-translational processing of the high mannose precursor (Mr 215,000) to yield the mature brush-border form (Mr 160,000) of LPH. Our results further indicate that LPH is synthesized as a single polypeptide precursor which is intracellularly cleaved to yield the mature brush border of LPH. The data presented suggest that this cleavage occurs during the translocation of the molecule across the Golgi complex. PMID- 3109376 TI - The mechanism of action of beta-glucosidase from Botryodiplodia theobromae Pat. AB - The activity of the high-molecular-weight beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) obtained from culture filtrates of Botryodiplodia theobromae Pat. was affected by added NaCl in such a way that an initial phase of stimulation was followed by a phase of rapid non-linear decrease in velocity and finally by a phase of slow linear decrease in velocity as the concentration of NaCl was increased. In the presence of 0.014 M-sodium acetate/acetic acid buffer (pH 5.0) there was a slight increase in enzymic activity in the presence of low concentrations of dioxan (up to about 10% dioxan) and a rapid decrease in enzymic activity at higher dioxan concentrations, but both effects were mitigated in the presence of 0.1 M buffer. The order of efficiency of added glucosyl acceptors in beta-glucosidase-catalysed reactions was found to be fructose greater than sucrose greater than glycerol greater than methanol. The enzyme was inactivated by the active-site-directed compound conduritol-B-epoxide; but this inactivation was concentration-dependent, was prevented by 10 mM-glucose, and involved an acidic group with pKa 4.3. A rate equation has been derived on the assumption of a mechanism of action involving a solvent-separated and an intimate glucosyl cation-carboxylate ion-pair intermediate and an alpha-glucosyl enzyme intermediate [Umezurike, G. M. (1981) Biochem. J. 199, 203-209]. Calculations based on the application of the derived rate equation and the calculated kinetic parameters show that the rate equation explains the peculiar properties of beta glucosidase in the presence of added glucosyl acceptors or of NaCl. PMID- 3109377 TI - The role of Ca2+ in regulating the catabolism of PAF-acether (1-O-alkyl-2-acetyl sn-glycero-3-phosphocholine) in rabbit platelets. AB - In the present study we have investigated the effect of changes in the concentration of cytosolic free Ca2+ ([Ca2+]i) on the deacetylation-reacylation of PAF-acether (alkylacetylglycerophosphocholine, alkylacetyl-GPC) by rabbit platelets. Washed platelets were incubated with alkyl[3H]acetyl-GPC ([3H]acetyl PAF) or [3H]alkylacetyl-GPC ([3H]alkyl-PAF) and [Ca2+]i was subsequently elevated by the addition of the ionophore A23187 or thrombin. The catabolism of PAF acether was studied by measuring the release of [3H]acetate or the formation of [3H]alkylacyl-GPC. The ionophore inhibited the release of [3H]acetate and the formation of [3H]alkylacyl-GPC with no accumulation of lyso-[3H]PAF, indicating that the deacetylation of PAF-acether was blocked. The effect of ionophore on the deacetylation of PAF-acether was parallel with the increase of [Ca2+]i and could be reversed by the addition of EGTA. In contrast with the prolonged inhibition evoked by ionophore, thrombin, which induced a transient elevation of [Ca2+]i, merely delayed the deacetylation of PAF-acether. Since intact platelets failed to convert exogenous lyso-PAF, the effect of Ca2+ on its acylation was investigated by using platelet homogenates. These experiments showed that the acylation of lyso-PAF was inhibited by the exogenously added Ca2+, with a maximum effect at 1 mM. When the formation of endogenous lyso-PAF from the labelled pool of alkylacyl GPC was examined, a prolonged increase in the concentration of lyso-PAF with a parallel and equally prolonged decrease in the cellular level of alkylacyl-GPC were observed after the addition of ionophore to intact platelets. The addition of EGTA reversed the effect of ionophore, thus permitting reacylation of lyso PAF. In contrast, only a transient change in the level of lyso-PAF and alkylacyl GPC was evoked by the addition of thrombin. Therefore we conclude that the inhibitory effect of Ca2+ on the deacetylation-reacylation of PAF-acether may have an important role in the regulation of its biosynthesis. PMID- 3109379 TI - beta-D-xylosides and their analogues as artificial initiators of glycosaminoglycan chain synthesis. Aglycone-related variation in their effectiveness in vitro and in ovo. AB - A series of aryl and alkyl O-beta-D-xylosides and their analogues with S, NH or CH2 in the glycosidic linkage were prepared and examined for their ability to act as artificial chain initiators of chondroitin (dermatan) sulphate synthesis in embryonic chick cartilage, foetal rat skin and 6-week-old-rat aorta under conditions where normal protein-core synthesis was inhibited by cycloheximide. For all these tissues in culture, phenyl O-beta-D-xyloside and phenyl beta-D thioxyloside were clearly more effective than the corresponding N-xyloside and homo-C-xyloside. Introduction of a carboxy group to the para position of their aglycone yielded derivatives with far lower initiator activity. In a concentration range lower than 0.1 mM, the effectiveness of alkyl beta-D thioxyloside was greatly influenced by the carbon number (n) of the alkyl group and was at a maximum at n = 7 or 8 for the cartilage, at n = 5 for the skin and at n = 4 for the aorta. In the beta-xyloside-treated cartilages, the average length of newly formed chondroitin sulphate chains reflected the chain-initiator activity of added xyloside, i.e. the higher the initiator activity, the shorter the average chain length. In the skin and aorta, none of the drugs could relieve the inhibition of heparan sulphate synthesis caused by cycloheximide. Fertilized hens' eggs were each injected on day 9 with 9.2 mumol of beta-xyloside and the skeletal systems of embryos were examined a week later. The embryos treated with beta-xylosides of relatively high initiator activity showed a 30-40% decrease in the overall growth rate of skeletons, whereas those treated with beta-xylosides of low initiator activity showed little or no decrease in the growth rate. The results are consistent with the notion that the observed change in skeletal morphology results mainly, if not completely, from beta-xyloside-induced synthesis of core-protein-free chondroitin sulphate, and further suggest that a procedure employing a series of beta-xyloside homologues with various initiator activities will furnish an easily applied criterion on which to test the specificity of xyloside action on biological processes. PMID- 3109378 TI - Physicochemical characterization of human intestinal lactase. AB - Human lactase was isolated from solubilized small-intestinal brush-border membranes by a combination of chromatography on concanavalin A-Sepharose, Bio-Gel 1.5m and chromatofocusing, with a yield of approx. 1% and a 750-fold purification. The enzyme appeared to be homogeneous on SDS/polyacrylamide-gel electrophoresis under both reduced and non-reduced conditions, with an apparent Mr of approx. 170,000. On gel filtration, however, it displayed an apparent Mr of approx. 380,000. The protein had a pI of 4.8, as judged by the chromatofocusing experiment, and had a lactase activity whose optimum is at pH 6.0. In addition to the beta-galactosidase activity, the protein also hydrolysed to various extents cellobiose, phlorizin, p-nitrophenyl beta-D-galactoside, p-nitrophenyl beta-D glucoside, o-nitrophenyl beta-D-galactoside and o-nitrophenyl beta-D-fucoside. Antisera had been raised against the purified enzyme in two rabbits. One of the antibody populations could inhibit the enzyme in a concentration-dependent manner. This antibody population was used to set up an antibody-bound Sepharose column for the use in an immunoaffinity purification of lactase from crude intestinal homogenate. A partially purified preparation of lactase could thus be obtained. The antibody population was also used to set up a radioimmunoassay for quantifying the enzyme. The competition assay could detect about 0.5 micrograms of lactase protein/ml. PMID- 3109380 TI - Sertoli-cell prostaglandin synthesis. Effects of (follitropin) differentiation and dietary vitamin E. AB - The synthesis of prostanoids by the Sertoli cell was assessed as part of a study on the role of vitamin E in maintaining spermatogenesis. Analyses of eicosanoid synthesis from endogenous substrate were carried out using freshly isolated Sertoli-cell-enriched preparations from both pre-pubertal and adult rats fed purified diets with and without vitamin E, as well as cells carried in primary culture. Freshly isolated cells from both the immature and fully differentiated adult testes produced PGI2 (prostaglandin I2) and PGE2, but PGF2 alpha was produced only by cells of the adult vitamin E-deficient rat. Cells from adult controls synthesized PGF2 alpha after primary culture. In contrast with other hormone responses of this cell, which are refractory in the adult, FSH (follitropin) potentiated prostaglandin production by freshly isolated cells of both immature and adult rats. The FSH response of Sertoli cells from immature animals did not change after primary culture. Adult cells were refractory to the hormone after culture, but the total amounts of prostaglandins produced by these cells were 10-fold higher than by either freshly isolated or cells of the immature in culture. Analogues of cyclic AMP did not potentiate prostaglandin synthesis. However, mepacrine, a phospholipase inhibitor, blocked the FSH effect. The finding that Sertoli cells synthesize prostaglandins and FSH enhances prostaglandin production implicates a potential role for eicosanoids in spermatogenesis and suggests that vitamin E may affect intratesticular regulators. PMID- 3109381 TI - A novel whey protein synthesized only in late lactation by the mammary gland from the tammar (Macropus eugenii). AB - A major whey protein which appears in milk from the tammar wallaby (Macropus eugenii) only during the second half of lactation (late lactation protein-A, LLP A) was purified to apparent homogeneity by ion-exchange chromatography and gel filtration. An Mr of 21,600 +/- 2000 was calculated from its amino acid composition. A computer-based comparison of the sequence of the first 69 amino acid residues with the Atlas of Protein Sequence data base showed no significant homology with known proteins. Antiserum to LLP-A was prepared in rabbits, and single radial immunodiffusion was used to measure the amounts of LLP-A in milk during the first 40 weeks of lactation. LLP-A was first detected at 26 weeks; thereafter its concentration increased abruptly, to reach a maximum of 26 g/l at approx. 36 weeks of lactation. Explants prepared from mammary gland biopsies at 20 and 35 weeks of lactation were exposed to [3H]amino acids for 8 h; immunoprecipitation of tissue extracts showed that, whereas the rate of casein synthesis was the same at both stages of lactation, LLP-A was synthesized only by the 35-week mammary gland. PMID- 3109382 TI - Human myeloma cells acquire resistance to difluoromethylornithine by amplification of ornithine decarboxylase gene. AB - Stepwise increments of the concentration of 2-difluoromethylornithine (DFMO), a mechanism-based irreversible inhibitor of mammalian ornithine decarboxylase (ODC), resulted in a selection of cultured human IgG-myeloma cells (Sultan cell line) capable of growing in the presence of up to 3 mM-DFMO. This capacity was associated with 10-fold increase in ODC activity in the dialysed extracts of drug resistant myeloma cells, markedly enhanced synthesis rate for ODC enzyme molecules, as revealed by a 20 min [35S]methionine labelling of cellular proteins, followed by specific immunoprecipitation and SDS/polyacrylamide-gel electrophoresis, dose-dependently increased expression of ODC mRNA in resistant cells (effective dose causing 50% inhibition), dose-dependent amplification of ODC gene sequences in a 9-kilobase-pairs EcoRI genomic DNA fragment, and (v) a 10 fold increase in the ED50 (effective dose causing 50% inhibition) for the anti proliferative action of DFMO in these myeloma cells. These results represent one of the few gene amplifications described in cultured human cells. PMID- 3109383 TI - Effect of polyamine depletion on macromolecular synthesis of the malarial parasite, Plasmodium falciparum, cultured in human erythrocytes. AB - DL-alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, prevented the increases in putrescine and spermidine, but not in spermine, in human erythrocytes infected with the malarial parasite Plasmodium falciparum. The addition of putrescine to these polyamine-depleted cultures restored the normal concentrations of spermidine, whereas that of putrescine even exceeded that of the control cultures. DFMO also inhibited the incorporation of radioactive amino acids into the proteins of parasitized erythrocytes. Electrophoresis on polyacrylamide gels revealed that the synthesis of some proteins was completely blocked by DFMO, but the synthesis of others was not affected. DFMO also caused a partial inhibition of RNA synthesis, and DNA synthesis was completely blocked in polyamine-depleted parasitized erythrocytes. It has been suggested that putrescine and/or spermidine are required for the synthesis of certain proteins in parasitized erythrocytes and that at least one of those proteins is related to the synthesis of DNA of the malarial parasite. It appears that polyamines regulate the schizogony process of P. falciparum. PMID- 3109384 TI - Pig pancreatic anhydro-elastase. Role of the serine-195 hydroxy group in the binding of inhibitors and substrate. AB - The binding constants of a number of ligands were measured for pancreatic elastase (PE) and anhydro-elastase (AE) in order to assess the contribution of Ser-195 to substrate and inhibitor binding by PE. AE was purified by affinity chromatography on a column containing immobilized turkey ovomucoid inhibitor. The AE had 0.1 +/- 0.1% of the activity of the native enzyme and contained 0.8 +/- 0.06 residue of dehydroalanine per molecule. A difference electron-density map, derived from an X-ray crystallographic analysis of AE, showed that the modified residue was Ser-195. The complexing of 3-carboxypropionyl-Ala-Ala-Ala-p nitroanilide (SAN) to the active site of AE was also demonstrated by X-ray diffraction analysis of an AE crystal soaked overnight with substrate. The nitroanilide moiety was not observed in the difference map. AE was shown to bind turkey ovomucoid inhibitor with a dissociation constant (Kd) of 0.3 +/- 0.06 microM compared with 0.10 microM for PE. The Kd of the AE-SAN complex (0.2 mM) was comparable with the Michaelis constant for SAN with PE (1.0 mM). A number of inhibitors, such as elastatinal, which forms a hemiketal adduct with PE, while others such as the beta-lactams, which function as acylators of the active-site serine residue, bound AE with a lower affinity than to PE. The binding of a peptidylchloromethane (acetyl-Ala-Ala-Pro-Ala-CH2Cl) to AE occurs without evidence for alkylation of histidine. The binding constants for benzoisothiazolinone and 3,4-dichloroisocoumarin to PE differed from their binding constants to AE by less than a factor of 4.0-fold. The contribution of the hydroxy group of Ser-195 to the binding of these inhibitors to PE in their non-covalent complexes is relatively small, even though they inactivate PE by an acylation mechanism. These results suggest that the hydroxy group on Ser-195 in PE is of secondary importance in the energetics of ligand binding, in contrast with its essential role in the catalytic properties of the enzyme. PMID- 3109385 TI - Phosphonic analogues of tyrosine and 3,4-dihydroxyphenylalanine (dopa) influence mushroom tyrosinase activity. AB - A series of phosphonic analogues of tyrosine and 3,4-dihydroxyphenylalanine (dopa) were synthesized in order to study their interaction with mushroom tyrosinase. 1-Amino-2-(3,4-dihydroxyphenyl)ethylphosphonic acid and 1-amino-2 (3,4-dimethoxyphenyl)ethylphosphonic acid turned out to be substrates for mushroom tyrosinase with Km values of 3.3 mM and 9.3 mM respectively. Shortening of the alkyl chain by one methylene group gave amino-(3,4 dihydroxyphenyl)methylphosphonic acid, one of the most powerful known inhibitors of this enzyme. This compound, racemic as well as in its optically active forms, exerts a mixed type of inhibition with an affinity for the enzyme one order of magnitude greater than that of the natural substrate. PMID- 3109386 TI - Anti-flavin antibodies. AB - Antibodies were elicited to FAD by using the hapten N-6-(6-aminohexyl)-FAD conjugated to the immunogenic carrier protein bovine serum albumin. Cross reactivity was determined by Ouchterlony double-diffusion analysis with N-6-(6 aminohexyl)-FAD coupled to rabbit serum albumin. Anti-FAD IgG was partially purified by (NH4)2SO4 precipitation followed by DEAE-cellulose/CM-cellulose and bovine serum albumin-agarose chromatography. The partially purified anti-FAD IgG fraction failed to inhibit the catalytic activities of the flavin-containing enzymes nitrate reductase, xanthine oxidase and succinate dehydrogenase, whereas enzyme activity could be inhibited by addition of antibodies elicited against the native proteins. However, the partially purified anti-FAD IgG fraction could be used as a highly sensitive and specific probe to detect proteins containing only covalently bound flavin, such as succinate dehydrogenase, p-cresol methylhydroxylase and monoamine oxidase, by immuno-blotting techniques. Detection limits were estimated to be of the order of femtomolar concentrations of FAD with increased sensitivity for the 8 alpha-N(3)-histidyl linkage compared with 8 alpha O-tyrosyl substitution. PMID- 3109387 TI - Comparison of arylsulphatases from Eimeria tenella (parasite) and chicken caecum (host). AB - Chicken caecal arylsulphatase was purified 700-fold by (NH4)2SO4 fractionation, concanavalin A-Sepharose and cyclic AMP-Sepharose chromatographies. The purified enzyme was a glycoprotein of Mr 97,000. It hydrolysed p-nitrocatechol sulphate, cerebroside 3-sulphate and ascorbic acid 2-sulphate and was strongly inhibited by Na2SO4 (Ki = 50 microM) and Na3PO4 (Ki = 20 microM). Arylsulphatase from Eimeria tenella sporozoites was purified 28-fold by (NH4)2SO4 fractionation. Arylsulphatase of E. tenella sporozoites was not a glycoprotein. It had an Mr of 49,000. It was inhibited by Na2SO4 (Ki = 300 microM), sodium phosphate (Ki = 90 microM) and heparin. It hydrolysed ascorbic acid 2-sulphate, but cerebroside 3 sulphate was not desulphated. The kinetic parameters of chicken caecal arylsulphatase were different from those of the E. tenella enzyme. PMID- 3109388 TI - Separation of multiple isomers of inositol phosphates formed in GH3 cells. AB - A high-performance-liquid-chromatography (h.p.l.c.) separation was developed, which resolves isomers of inositol monophosphate (IP), inositol bisphosphate (IP2), and inositol trisphosphate (IP3) in a single run. In GH3 cells labelled with [3H]inositol, treated with Li+ and thyrotropin-releasing hormone (TRH), radiolabelled components identified as inositol 1-phosphate (I1P), inositol 2 phosphate (I2P), inositol 4-phosphate (I4P), inositol 1,4-bisphosphate [I(1,4)P2], inositol 1,3,4-trisphosphate [I(1,3,4)P3] and inositol 1,4,5 trisphosphate [I(1,4,5)P3] are present, as are multiple unidentified IP2 peaks. After TRH stimulation, both I1P and I4P increase, the increase in I4P preceding that of I1P; I(1,4)P2 and an unknown IP2 increase; and both I(1,3,4)P3 and I(1,4,5)P3 increase, the increase in I(1,4,5)P3 being rapid and transient, whereas the increase in I(1,3,4)P3 is slower and more sustained. The most rapidly appearing inositol phosphates produced after TRH stimulation are I(1,4)P2 and I(1,4,5)P3. PMID- 3109389 TI - Thyrotropin-releasing hormone activates Na+/H+ exchange in rat pituitary cells. AB - The effects of thyrotropin-releasing hormone (TRH) and 12-O-tetradecanoylphorbol 13-acetate (TPA) on cytosolic pH (pHi) were studied on GH4C1 pituitary cells loaded with the fluorescent pH indicator bis(carboxyethyl)carboxyfluorescein (BCECF) and the fluorescent Ca2+ indicator quin2. TRH, which was minimally effective at around 10(-9) M, and TPA, 100 nM, produced very small elevations in pHi of about 0.05 pH units from the normal basal resting pHi of GH4C1 cells of around 7.05. The effects were more marked after acid-loading the cells using 1 micrograms of nigericin/ml. Preincubation with amiloride or replacing the extracellular Na+ with choline+ completely blocked the elevations stimulated by TRH or TPA, consistent with an activation of the Na+/H+ antiport mechanism. The effects were completely independent of the cytoplasmic free calcium concentration ([Ca2+]i). The calcium ionophore ionomycin produced an elevation in [Ca2+]i with no concomitant effect on pHi, and amiloride, although completely inhibiting the pH change stimulated by TRH, failed to affect the initial stimulated [Ca2+]i transient. Although the data are consistent with an elevation in pHi by TRH which is caused by stimulation of a protein kinase C and subsequent activation of the antiporter, the rapidity of the onset of the pHi response to TRH could not be mimicked by a combination of TPA and ionomycin. These results, together with previous findings which show that secretion can be mimicked by TPA and ionomycin, suggest that TRH-stimulated Na+/H+ exchange plays no part in the acute stimulation of secretion, but that TRH increases the pH-sensitivity of the antiport system during increased synthesis of prolactin and growth hormone. PMID- 3109390 TI - Purine deoxynucleosides and adenosine dialdehyde decrease 5-amino-4 imidazolecarboxamide (Z-base)-dependent purine nucleotide synthesis in cultured T and B lymphoblasts. AB - Deoxyadenosine (dAdo) and deoxyguanosine (dGuo) decrease methionine synthesis from homocysteine in cultured lymphoblasts; because of the possible trapping of 5 methyltetrahydrofolate this could lead to decreased purine nucleotide synthesis. Since purine deoxynucleosides could also inhibit purine synthesis de novo at an early step not involving folate metabolism, we measured in azaserine-treated cells 5-amino-4-imidazolecarboxamide (Z-base)-dependent purine nucleotide synthesis using [14C]formate. In the T lymphoblasts, Z-base-dependent purine nucleotide synthesis was decreased 26% by 0.3 microM-dAdo, 21% by 1 microM-dGuo and 28% by 1 microM-adenosine dialdehyde, a potent S-adenosylhomocysteine hydrolase inhibitor; homocysteine fully reversed the inhibitions. The B lymphoblasts were considerably less sensitive to the deoxynucleoside-induced decrease in Z-base-dependent purine nucleotide synthesis, with 100 microM-dAdo required for significant inhibition and no inhibition by dGuo at this concentration; homocysteine partly reversed the inhibition by dAdo. The observed decrease in Z-base-dependent purine nucleotide synthesis could not be attributed either to dUMP depletion changing the folate pools or to decreased ATP availability because dUrd was without effect and during the experimental period the intracellular ATP concentration did not change significantly. Cells with 5,10 methylenetetrahydrofolate reductase deficiency were relatively resistant to inhibition of Z-base-dependent purine nucleotide synthesis by dAdo and adenosine dialdehyde. Our results suggest that deoxynucleosides decrease purine nucleotide synthesis by trapping 5-methyltetrahydrofolate. PMID- 3109392 TI - Effect of alpha-difluoromethylornithine on DNA methylation in murine erythroleukaemic cells. Relationship to stimulation of induced differentiation. AB - Murine erythroleukaemic (MEL) cells cultured with alpha-difluoromethylornithine (DFMO) accumulated decarboxylated S-adenosylmethionine(decarboxylated AdoMet). In the absence of the inducer hexamethylenebisacetamide (HMBA), this accumulation of decarboxylated AdoMet was associated with a concomitant and proportional increase in DNA hypomethylation. In the presence of HMBA, DFMO, which stimulates the erythrodifferentiation of MEL cells, enhanced the differentiation-associated DNA hypomethylation. However, this differentiation-associated DNA hypomethylation was neither temporally nor quantitatively correlated with the accumulation of decarboxylated AdoMet in these cells. Therefore DFMO probably stimulates the HMBA induced differentiation of MEL cells and the associated DNA hypomethylation via the effect of this drug on polyamine biosynthesis. PMID- 3109391 TI - Zymosan-induced release of inositol phosphates at resting cytosolic Ca2+ concentrations in macrophages. AB - Hydrolysis of polyphosphoinositides by phosphodiesterase has been demonstrated to be involved in the control of cytosolic Ca2+ concentrations. The stimulation of Ca2+ ionophores of the release of inositol phosphates in macrophages, and other cells, together with the Ca2+ requirements for zymosan-induced phospholipase C activation, make unclear the relationship between Ca2+ mobilization and polyphosphoinositide hydrolysis. The results in the present paper strongly suggest that, for zymosan-induced phospholipase C activation, a previous increase in cytosolic Ca2+ is not a required event. These results also show that zymosan activated release of inositol phosphates may be mediated by a guanine-nucleotide binding protein. PMID- 3109393 TI - Characterization and physiological function of glutathione reductase in Euglena gracilis z. AB - The purified glutathione reductase was homogeneous on polyacrylamide-gel electrophoresis. It had an Mr of 79,000 and consisted of two subunits with a Mr of 40,000. The activity was maximum at pH 8.2 and 52 degrees C. It was specific for NADPH but not for NADH as the electron donor; the reverse reaction was not observed. The Km values for NADPH and GSSG were 14 and 55 microM respectively. The enzyme activity was markedly inhibited by thiol inhibitors and metal ions such as Hg2+, Cu2+ and Zn2+. Euglena cells contained total glutathione at millimolar concentration. GSH constituted more than 80% of total glutathione in Euglena under various growth conditions. Glutathione reductase was located solely in cytosol, as were L-ascorbate peroxidase and dehydroascorbate reductase, which constitute the oxidation-reduction cycle of L-ascorbate [Shigeoka et al. (1980) Biochem. J. 186, 377-380]. These results indicate that glutathione reductase functions to maintain glutathione in the reduced form and to accelerate the oxidation-reduction of L-ascorbate, which scavenges peroxides generated in Euglena cells. PMID- 3109394 TI - Intracellular mechanisms in the activation of human platelets by low-density lipoproteins. AB - Low-density lipoproteins (LDL) have been shown to cause aggregation of human blood platelets at concentrations above 2 g of protein/l. The secretion of the contents of platelet dense granules was detected, but not that of the lysosomes. LDL gave rise to a mobilization of [3H]arachidonic acid from phospholipids and the appearance of products of the cyclo-oxygenase pathway after only 10 s. LDL promoted aggregation was inhibited by both aspirin and indomethacin. There was an increase in 3H-labelled diacylglycerols and the phosphorylation of 47 kDa proteins. LDL therefore shares at least some of the mechanisms of stimulus/response coupling with those of other agonists. PMID- 3109395 TI - Purification and properties of a germination-specific cortex-lytic enzyme from spores of Bacillus megaterium KM. AB - Two peptidoglycan-lytic enzyme activities were isolated from spores of Bacillus megaterium KM. Surface-bound lytic enzyme was extracted from dormant spores and hydrolysed a variety of peptidoglycan substrates including isolated spore cortex, but did not cause refractility changes in permeabilized spores. Germination specific lytic enzyme activity appeared early in germination and had minimal activity on isolated peptidoglycan substrates, but caused refractility changes in permeabilized spores of several Bacillus isolated peptidoglycan substrates, but caused refractility changes in permeabilized spores of several Bacillus species. The germination-specific lytic enzyme was shown to be a heat-sensitive 29 kDa protein with maximal activity at pH 6.5. It catalysed post-commitment muramic acid delta-lactam synthesis and displayed an inhibitor profile similar to that for post-commitment A600 loss. The relationship of the germination-specific enzyme to a recently proposed model of spore germination is discussed. PMID- 3109396 TI - Cloning of a human liver microsomal UDP-glucuronosyltransferase cDNA. AB - A cDNA clone (HLUG 25) encoding the complete sequence of a human liver UDP glucuronosyltransferase was isolated from a lambda gt11 human liver cDNA library. The library was screened by hybridization to a partial-length human UDP glucuronosyltransferase cDNA (pHUDPGT1) identified from a human liver pEX cDNA expression library by using anti-UDP-glucuronosyltransferase antibodies. The authenticity of the cDNA clone was confirmed by hybrid-select translation and extensive sequence homology to rat liver UDP-glucuronosyltransferase cDNAs. The sequence of HLUG 25 cDNA was determined to be 2104 base-pairs long, including a poly(A) tail, and contains a long open reading frame. The possible site of translation initiation of this sequence is discussed with reference to a rat UDP glucuronosyltransferase cDNA clone (RLUG 38). PMID- 3109397 TI - Pea (Pisum sativum) diamine oxidase contains pyrroloquinoline quinone as a cofactor. AB - Diamine oxidase was prepared from pea (Pisum sativum) seedlings by a new purification procedure involving two h.p.l.c. steps. We studied the optical and electrochemical properties of the homogeneous enzyme and also analysed the hydrolysed protein by several methods. The data presented here suggest that the carbonyl cofactor of diamine oxidase is firmly bound pyrroloquinoline quinone. PMID- 3109398 TI - Probing the sequence-specific interaction of the cyclic AMP receptor protein with DNA by site-directed mutagenesis. AB - Mutants in the DNA-binding helix of the cyclic AMP receptor protein (CRP), as well as mutants in a synthetic DNA-binding site derived from the sequence in the lac regulatory region, have been constructed by oligonucleotide-directed mutagenesis, and used to study the effect of selected amino acid substitutions on CRP-mediated transcriptional activity and on sequence-specific DNA binding. It has been shown that mutation of Arg-180 to Lys or Leu abolishes both CRP-mediated expression of beta-galactosidase in vivo and CRP binding of DNA as measured by immunoprecipitation. In contrast, the mutation of Arg-185 to Leu or Lys and the mutation of Lys-188 to Leu does not appear to influence these two parameters significantly. On the DNA side, both substitutions studied, namely the exchange of the G . C base pair in position 2 of the consensus T1G2T3G4A5 motif into an A . T base pair and the exchange of the A . T base pair in position 5 for a G . C base pair, abolish specific binding. Implications of these findings with respect to the present models for specific CRP-DNA recognition are discussed. PMID- 3109399 TI - Quaternary structure of erythrocruorin from the nematode Ascaris suum. Evidence for unsaturated haem-binding sites. AB - The quaternary structure of erythrocruorin from the nematode Ascaris suum was studied. The native protein had a sedimentation coefficient, at a protein concentration of 1 mg/ml, of 11.6 +/- 0.3 S and an Mr, as determined by sedimentation equilibrium, of 332,000 +/- 17,000. SDS/polyacrylamide-gel electrophoresis gave one band with a mobility corresponding to an Mr of 43,000 +/ 2000. The Mr of the polypeptide chain was determined to be 41,600 +/- 1,500 by sedimentation equilibrium in 6 M-guanidinium chloride and 0.1 M-2 mercaptoethanol. Cross-linking with glutaraldehyde followed by SDS/polyacrylamide gel electrophoresis yielded a maximal number of eight bands. The haem content of Ascaris erythrocruorin was observed to vary from one preparation to another. This finding was shown to be due to non-realization of the full binding capacity for haem. By titration with haemin, the haem content was found to attain a maximal value of 2.86 +/- 0.14%, corresponding to a minimal Mr per haem group of 21,000 +/- 1,000. Our findings indicate that Ascaris suum erythrocruorin is composed of eight identical polypeptide chains, carrying two haem sites each. PMID- 3109401 TI - Studies on the biotin-binding site of avidin. Lysine residues involved in the active site. AB - Egg-white avidin was treated with 1-fluoro-2,4-dinitrobenzene. Modification of an average of one lysine residue per avidin subunit caused the complete loss of biotin binding. Tryptic peptides obtained from the 2,4-dinitrophenylated avidin were fractionated by reversed-phase h.p.l.c. Three peptides contained the 2,4 dinitrophenyl group. Amino acid analysis revealed that lysine residues 45, 94 and 111 are modified and probably comprise part of the biotin-binding site. PMID- 3109402 TI - Cloning of reticulocyte lipoxygenase mRNA. PMID- 3109400 TI - Expression of UDP-N-acetylgalactosamine: beta-galactose beta 1,4-N acetylgalactosaminyltransferase in functionally defined T-cell clones. AB - To measure UDP-N-acetylgalactosamine: beta-galactose beta 1,4-N acetylgalactosaminyltransferase (beta 1,4-GalNActransferase) in crude cell and tissue extracts we designed an assay containing UDP-[3H]N-acetylgalactosamine as donor and biotinylated human glycophorin A as an acceptor. After incubation the labelled acceptor was separated by the use of avidin-agarose from extract-derived endogenous acceptors. This assay permitted one to measure specifically the beta 1,4-GalNActransferase in crude extracts. This glycosyltransferase has previously been shown to be involved in the biosynthesis of Vicia villosa (hairy winter vetch)-lectin (VV)-binding sites of the murine cytotoxic T-cell line B6.1. Since VV-binding sites are a distinct marker for the cytotoxic subclass of murine T lymphocytes, we used this assay to determine enzyme levels in a panel of functionally defined murine T-cell clones. Non-cytolytic T-cell lines generally have low activity, whereas most cytotoxic lines have high levels of activity. However, one cytotoxic T-cell line does not express the enzyme, although it has large numbers of VV-binding sites. This suggests the existence of another type of VV-binding sites which is independent of the beta 1,4-GalNActransferase in some cytotoxic-T-lymphocyte lines. The enzyme was also assayed in a variety of other tissues and found to have a very high activity in the intestine but a low activity in most other tissues. This was in considerable contrast with the ubiquitously high expression of UDP-GalNAc:peptide alpha 1-GalNActransferase. Therefore, the beta 1,4-GalNActransferase seems to be regulated during differentiation. PMID- 3109404 TI - Metabolism of polyenoic fatty acids by red blood cells. PMID- 3109403 TI - Maturational breakdown cascade of mitochondria in reticulocytes. PMID- 3109405 TI - Modelling the reaction mechanism of the reticulocyte lipoxygenase. PMID- 3109406 TI - Stimulation by calcium of glucose uptake and lactate production in pigeon erythrocytes. AB - The rate of glucose conversion into phosphorylated or charged intermediates was determined and related to lactate output and ATP levels. The calcium ionophore A23187 stimulated strongly the production of lactate in pigeon erythrocytes. It required the presence of calcium and simultaneously ATP levels fell down in red cells. The rate of glucose uptake by pigeon erythrocytes was measured as the conversion of [U-14C]glucose into phosphorylated or charged intermediates. A23187 increased the rate of glucose uptake and required the presence of micromolar calcium concentrations. Neither glucose uptake nor lactate production could be related to the decrease of cellular ATP. The results suggest that changes in intracellular calcium alone can stimulate glucose uptake and lactate production. PMID- 3109407 TI - Effects of oxygen and mixing on red cells stored in plastic bags at +4 degrees C. AB - When red cells are stored in plastic (PVC) containers the penetration of blood gases--O2 entering into and CO2 escaping out of the blood units--influences the red cell metabolism; ATP and energy charge are better maintained at anaerobic storage. When sedimented cells are stored unmixed, the blood gas diffusion is markedly restricted and the concentration of metabolites is rapidly increasing. This leads to disturbed metabolism, increased microvesiculation and decreased erythrocyte fluidity. In a blood transfusion service producing blood components, this is likely to have an important impact on the quality of the red cells. It seems advisable to store red cells in a sufficiently large volume of a suspension medium (such as the SAGM solution) and apply mixing during storage. PMID- 3109408 TI - Stereoselective formation of benzo(c)phenanthrene (+)-(3S,4R) and (+)-(5S,6R) oxides by cytochrome P450c in a highly purified and reconstituted system. AB - The principal oxidative metabolites formed from benzo(c)phenanthrene (B(c)Ph) by the cytochromes P450 in liver microsomes from control and treated rats are the 3,4- and 5,6-arene oxides. A procedure is described which allows determination of the enantiomer composition and absolute configuration of these arene oxides based on HPLC separation of isomeric thiolate adducts formed with N-acetyl-L-cysteine in base. Incubation of [3H]-B(c)Ph with highly purified cytochrome P450c in a reconstituted monooxygenase system followed by trapping of the metabolically formed arene oxides as above indicated that the 3,4-oxide was predominantly the (+)-(3S,4R)-enantiomer (90%) and that the 5,6-oxide consisted mainly of the (+) (5S,6R)-enantiomer (76%). The results are discussed in terms of their implications about the catalytic binding site of cytochrome P450c. PMID- 3109409 TI - The role of 7-mercaptoheptanoylthreonine phosphate in the methylcoenzyme M methylreductase system from Methanobacterium thermoautotrophicum. AB - The structure of component B of the methylcoenzyme M methylreductase system from Methanobacterium thermoautotrophicum was recently found to be 7 mercaptoheptanoylthreonine phosphate (HS-HTP). Three potential roles for this cofactor were considered. First, a methyl thioether derivative of the cofactor was synthesized to investigate its possible role as a methyl donor. This derivative was found to be incapable of acting as a substrate for methanogenesis and proved inhibitory. Secondly, an adenylated form of the cofactor was considered as the potential active form of the coenzyme. This possibility was ruled out based upon collaborative observations with Ankel-Fuchs et al. (FEBS Lett., in press) that HS-HTP is required by the methylreductase system even when ATP is not. Finally, HS-HTP was found to act as a reductant in a partially purified methylreductase preparation that was incubated under nitrogen. The rate of methane production from HS-HTP exceeded that from other thiols or hydrogen. PMID- 3109410 TI - Two independent domains of factor VIII co-expressed using recombinant vaccinia viruses have procoagulant activity. AB - Using recombinant DNA technology, the NH2 and COOH terminal domains of the human Factor VIII molecule were co-expressed in baby hamster kidney 21 (BHK21) cells using the vaccinia virus system. Procoagulant activity was detectable in cell supernatants, thus suggesting that the central portion present in the FVIII protein (domain B) is not required for FVIII function. PMID- 3109411 TI - A novel inositol glycophospholipid (IGPL) and the serum dependence of its metabolism in bovine adrenocortical cells. AB - Adrenocortical cells in primary culture actively incorporated [3H]-inositol into phosphatidylinositol (PI) and its mono (PIP) and bisphosphate (PIP2) derivatives. In addition to these well known phosphoinositides, a inositol-containing component was detected in the cell lipid extract when analyzed by proper chromatographic systems. This component was also labeled when the cells were provided with 32P or radioactive fatty acids and a distinctive character was its ability to incorporate [3H]-glucosamine. This novel phospholipid was thus characterized as an inositol glycophospholipid (IGPL). Study of IGPL metabolism in adrenocortical cells disclosed that the presence of serum in the culture medium strikingly increased glucosamine as well as inositol incorporation by a factor of about 10 and 5, respectively, within 36 hours. These observations suggest that IGPL turnover rate, especially at the level of its inositol-glycan moiety may be regulated by extracellular signals. A possible role of IGPL in membrane signalling systems and cell regulation remains to be clarified. PMID- 3109412 TI - Phorbol esters inhibit phosphate uptake in opossum kidney cells: a model of proximal renal tubular cells. AB - The effects of phorbol esters and diacylglycerol on phosphate uptake in opossum kidney (OK) cells were investigated to assess the possible role of Ca2+ activated, phospholipid dependent protein kinase (protein kinase C) on renal phosphate handling. OK cells are widely used as a model of proximal renal tubular cells and are reported to possess a Na+-dependent phosphate transport system. Phorbol-12,13-dibutyrate (PDBu) inhibited phosphate uptake. This inhibitory effect was synergistically enhanced with A23187. 4 beta-phorbol 12,13-didecanoate inhibited phosphate uptake, while 4 alpha-phorbol 12,13-didecanoate did not. 1 oleoyl-2-acetyl-glycerol (OAG), a synthetic diacylglycerol, also exhibited an inhibitory effect on phosphate uptake. These data suggest the possible involvement of protein kinase C in proximal renal tubular phosphate transport. PMID- 3109413 TI - Novel Leu-Lys-specific peptidase (Leulysin) produced by gel-entrapped yeast cells. AB - Saccharomyces cerevisiae cells entrapped with a neutral hydrophilic photo crosslinkable resin prepolymers specifically excreted into a cultured medium a new type of a peptidase, which cleaved Leu-Lys bond of alpha-mating factor. The enzyme was purified by membrane filtration followed by ion exchange chromatography and gel filtration chromatography. The purified enzyme showed a strict substrate specificity on internal Leu-Lys bond. Leu-Lys bond near terminus of a molecule and Leu-X and X-Lys bonds examined so far were not hydrolyzed by the enzyme. PMID- 3109414 TI - The role of platelet cyclooxygenase and lipoxygenase pathways in tumor cell induced platelet aggregation. AB - Walker 256 carcinosarcoma cells induce the aggregation of rat platelets and concomitant production of eicosanoid metabolites (e.g., 12 hydroxyeicosatetraenoic acid, thromboxane A2). Cyclooxygenase inhibitors, but not lipoxygenase inhibitors, were able to inhibit platelet aggregation induced in vitro by low concentrations of agonists. At high agonist concentrations, neither cyclooxygenase nor lipoxygenase inhibitors affected platelet aggregation; however the combination of both inhibitors resulted in inhibition of aggregation. Also, a low concentration of agonist induced minimal eicosanoid metabolism, whereas a high concentration resulted in increased eicosanoid metabolism. These inhibitors, at the doses tested, did not inhibit protein kinase C activity. PMID- 3109415 TI - Synergism of tumor necrosis factor and interferon-gamma in induction of differentiation of human myeloblastic leukemic ML-1 cells. AB - Natural or recombinant human tumor necrosis factor (TNF) induced NBT-reducing activity of ML-1 cells in a dose-dependent manner. Interferon-gamma (IFN-gamma) induced NBT-reducing activity only marginally. However, when IFN-gamma was combined with TNF, induction of NBT-reducing activity was remarkably increased. IFN-alpha or -beta had almost no effect on the induction of NBT-reducing activity of ML-1 cells, either alone or in combination with TNF. Treatment with both TNF and IFN-gamma synergistically enhanced morphological changes, growth inhibition and activity of Fc receptors, and NBT reduction in ML-1 cells, but not phagocytic activity. The TNF treated cells were classified as macrophage-like by morphology, and by lineage-specific alpha-naphthyl acetate esterase stain. The results indicate that combinations of TNF and IFN-gamma act synergistically in the induction of differentiation of human myeloblastic ML-1 cells. PMID- 3109416 TI - Improved detection limits in an organic mass spectrometer using a combination of matrix free FAB and photodiode array detection. AB - Scanning mass spectrometers suffer from the disadvantage of monitoring only one mass at any particular time in contrast to mass spectrographs which allow the simultaneous detection of an extended mass range. Historically such mass spectra were recorded by directing the ion beam onto a photographic plate which was subsequently developed and interpreted. The introduction of electronic devices such as the photodiode array enabled the development of imaging detectors capable of real time readout, so that a range of masses can be detected and rapidly processed using a computer system. This work uses such a detector in combination with a double focusing MS50RF mass spectrometer for the parallel detection of a limited mass range. PMID- 3109417 TI - Effects of teleocidin on the morphology and c-myc expression of hepatoma cells which are not inhibited by protein kinase antagonists. AB - PLC/PRF/5 hepatoma cells cultured with a tumor promoter teleocidin showed polygonal cellular appearance with many vacuole-like structures, and reduced both c-myc mRNA level and growth rate. These teleocidin effects were partly mimicked by sodium butyrate but not by a protein kinase C stimulant 1-oleoyl-2 acetylglycerol(OAG). Protein kinase C inhibitor 1-(5-isoquinolinyl-sulfonyl)-2 methyl-piperazine(H7), calmodulin-dependent protein kinase antagonist N-(6 aminohexyl)-5-chloro-1-naphthalene sulfonamide(W7) and topoisomerase II inhibitor novobiocin failed to inhibit the effects of teleocidin. These results may suggest the presence of still unknown biochemical pathways which mediate the actions of teleocidin. PMID- 3109418 TI - Calcium ion-dependent proliferation of L1210 cells in culture. AB - Maximum growth of L1210 cells in culture required the presence of free extracellular calcium ions. Reducing the free extracellular calcium ion concentration with EGTA served to decrease the growth rate of the cells. The decrease in cell growth was not due to cell death but rather due to the "pile-up" of the L1210 cells in the GO/Gl phase of the cell cycle. With the readdition of excess calcium ions, there was a lag period of 3 to 6 hours before the L1210 cells initiated DNA synthesis or transited from the G0/G1 phase to S-phase. Cells enriched for S and G2/M phase by elutriation and which were incubated in EGTA containing culture medium, continued through the cell cycle and were blocked in GO/Gl. These data indicate that the proliferation of L1210 cells in culture requires a calcium ion-dependent process to allow movement from the G0/G1 to S phase of the cell cycle. PMID- 3109419 TI - Differences between Saccharomyces cerevisiae and Bacillus subtilis in secretion of human lysozyme. AB - Saccharomyces cerevisiae secreted human lysozyme in the medium as an active form when the signal peptides of chicken lysozyme and a chicken lysozyme-Aspergillus awamori glucoamylase hybrid were used, whereas it did not synthesize any human lysozyme protein by using the signal peptide of A. awamori glucoamylase. The secreted lysozyme was easily purified and crystallized. On the other hand, Bacillus subtilis secreted an inactive human lysozyme, which seemed to have incorrect disulfide bonds, with the signal peptide of amylase and its mutants. The free energy changes for the membrane translocation of the signal peptides are related to the secretion of human lysozyme in S. cerevisiae, but not in B. subtilis. These results indicate that differences exist between S. cerevisiae and B. subtilis in the secretion of human lysozyme. PMID- 3109420 TI - Mechanism of cytotoxicity of aflatoxin B1: role of cytochrome P1-450. AB - A mouse hepatoma cell line, Hepa-1, is highly sensitive to the toxic effects of Aflatoxin B1 (AFB1). Half maximal survival (LD50) of cells occurs at 0.068 ug AFB1/ml. Benzo(a)anthracene, which induces aryl hydrocarbon hydroxylase and cytochrome P1-450 in Hepa-1, causes a slight increase in the toxicity of AFB1 (LD50 = 0.034 ug/ml). An aryl hydrocarbon hydroxylase- and cytochrome P1-450 deficient mutant of Hepa-1 is, however, over 100 times more resistant to AFB1 than Hepa-1. Almost no decline in survival is observed at 5 ug AFB1/ml. Cytochrome P1-450 thus effects strongly on the cytotoxicity of AFB1 in these cells. The basal activity in Hepa-1 is enough to elicit an almost full toxic effect. AFB1, although a substrate for cytochrome P1-450, does not act as an inducer of aryl hydrocarbon hydroxylase. PMID- 3109421 TI - Inhibition of urea cycle enzymes by lysine and saccharopine. AB - Crude and purified preparations of argininosuccinate synthetase, argininosuccinate lyase and arginase were subjected to inhibition studies with L lysine and saccharopine. Saccharopine proved to be the more potent inhibitor of argininosuccinate synthetase and lyase, whereas lysine had more effect on arginase. Similar results were found with pure enzyme and crude preparations. Computer analysis of the results suggested that inhibition of urea cycle enzymes by saccharopine and lysine might have contributed to the high levels of citrulline found in a human patient with saccharopinuria, a defect of saccharopine metabolism, but that this was unlikely to be the sole explanation. PMID- 3109422 TI - Quenching of the fluorescence of actin modified at lysine-61. AB - The fluorescence of actin modified with fluorescein isothiocyanate at Lys-61 is quenched in the presence of iodide. The approximate second order rate constant for quenching is 9 X 10(-8) M-1 s-1, which approaches that for a diffusion limited process. However, a measurable degree of protection is provided to the fluorescein group by the protein structure around it. A tryptic digest of the modified actin is more susceptible to quenching than is the native protein. Free fluorescein is even more vulnerable. The addition of deoxyribonuclease I to the modified actin reduces the susceptibility of the fluorescence to quenching by only a small degree. PMID- 3109423 TI - Comparison of aldose reductase inhibitors in vitro. Effects of enzyme purification and substrate type. AB - Aldose reductase (EC 1.1.1.21) was purified approximately 5000-fold from bovine lens by ammonium sulphate fractionation and chromatography on DEAE-Sephacel and Matrex OA. Inhibition of this enzyme was found to depend upon the assay substrate. Tested against the purest form of enzyme, the inhibitor Sorbinil gave IC50 values of approximately 100 microM with the model substrate 4 nitrobenzaldehyde (4NB) and 0.4-1.4 microM with the physiological substrate glucose. A similar effect of substrate was found for the inhibitor Statil (IC50 450-750 nM with 4NB, 26-71 nM with glucose substrate). The implications of these results towards the assessment of aldose reductase inhibitors in vitro are discussed. PMID- 3109424 TI - Uptake and binding of teniposide (VM26) in Krebs II ascites cells. AB - With [3H] VM26 as marker, the uptake and binding of teniposide have been made in cells of Krebs II ascitic tumors. The intracellular accumulation of drug displayed a passive diffusion and a saturation kinetics with an apparent Michaelis-Menten constant of 37.54 10(-6) M and a flux of 13.4 nM/min/mg of protein. VM26 was rapidly taken and an equilibrium was established with the extracellular drug in about 30 min. The steady-state accumulation was diminished by Na+ and Ca2+ absence and VP16-213, whereas, K+ and Mg2+ have no effect. Energy dependence of the system was characterized by a Q10 of 1.75 +/- 0.2 and the uptake was reduced by ouabain and iodoacetamide, when 2-4-dinitrophenol and glucose absence were without appreciable change. The study of the efflux showed that about 87% of the uptaken drug was removed, the residual amount being probably irreversibly bound. The intracellular accumulation of the drug was associated with various cell organelles, however, only the nuclear fraction demonstrated a high affinity binding. PMID- 3109425 TI - Generation of photoemissive species by mitomycin C redox cycling in rat liver microsomes. AB - Generation of reactive oxygen species during redox cycling is thought to be involved in the chemotherapeutic action of quinone anticancer drugs. A clinically used agent which contains a quinone moiety is mitomycin C (Mit C). With isolated rat liver microsomes we detected photoemissive species during Mit C-induced redox cycling. After addition of reduced glutathione (GSH) a large increase in Mit C induced chemiluminescence was observed. The increase of photoemission in deuterium oxide as well as greater than 90% of intensity at wavelengths greater than 610 nm suggest that singlet oxygen is a photoemissive species generated by this system. Glutathione disulfide (GSSG) accumulates during the reaction. We propose that superoxide anion radicals formed during redox cycling of Mit C react with GSH. Generation of glutathionyl radicals followed by oxygen addition then leads to the formation of photoemissive species and GSSG. PMID- 3109426 TI - Stimulation of vascular prostacyclin by SKF 525-A (proadifen) and related compounds. AB - SKF 525-A (proadifen), a well-known inhibitor of drug metabolism and cytochrome P 450 activity, stimulated the release of prostacyclin (PGI2) from the rabbit aorta in vitro. The threshold concentration producing a detectable effect was 20 microM; the time course of SKF 525-A action exhibited particular features- progressive onset, long duration and slow reversibility--distinct from those of other stimuli (ADP, ionophore A23187 f.i.). The PGI2-stimulating activity of SKF 525-A was characterized by specific structural requirements: activity was abolished by the deletion of the terminal propyl group and increased by its elongation into an isobutyl group; chlorination of the phenyl groups increased the potency. SKF 525-A increased the production of PGI2 by cultured endothelial cells from bovine aorta and human umbilical vein, but had no effect on cultured smooth muscle from the bovine aortic media. Stimulation of PGI2 release could be explained by an increased availability of free arachidonic acid, which was probably independent from cytochrome P-450 inhibition. In human platelets, SKF 525-A inhibited prostaglandin and thromboxane production induced by A23187, thrombin and ADP. Simultaneous stimulation of endothelial PGI2 and inhibition of platelet TxA2 represents an original pharmacological profile: SKF 525-A might thus constitute the prototype of a new class of antiplatelet drugs. PMID- 3109427 TI - Potentiation of ara-C induced cytotoxicity by hydroxyurea in LoVo colon carcinoma cells. AB - The present study was undertaken to determine whether cytotoxicity by 1-beta-D arabinofuranosylcytosine (ara-C) in LoVo colon carcinoma cells, which are resistant to high concentrations of ara-C, would be enhanced by concurrent exposure to hydroxyurea (HU). Since mechanisms underlying the effects of HU on ara-C induced cytotoxicity are unclear, we also evaluated the effect of HU on the incorporation of ara-C into DNA, as well as potential consequences of misincorporation. Our results demonstrate that HU synergistically enhances cytotoxicity by ara-C in these cells. This effect was not present when HU was combined with aphidicolin, an agent that resembles ara-C in competing with dCTP for binding to polymerase alpha but that is not incorporated into DNA. Further, cells exposed to HU and ara-C incorporated up to 5-fold as much ara-C into DNA as cells solely treated with ara-C. While the extent of inhibition of DNA synthesis was comparable with cells exposed to HU and aphidicolin as those treated with HU and ara-C, recovery of DNA synthesis was delayed more significantly by the latter combination. These findings suggest that HU synergistically potentiates ara-C induced cytotoxicity by enhancing incorporation of ara-C in LoVo cell DNA. PMID- 3109428 TI - Effect of permanently charged and uncharged dopaminergic agonists on the potassium-induced release of [3H]acetylcholine from striatal slices. AB - The effects of chemical analogs of dopamine, which are permanently charged or which lack a net positive charge, on the potassium-evoked release of [3H]acetylcholine from mouse striatal slices were studied in order to determine whether a positive charge on the dopamine agonist molecule is required to activate dopaminergic receptors. The striatal slices were first preincubated with [3H]choline, transferred to a superfusion chamber, and then superfused in physiological medium. [3H]Acetylcholine release was evoked by exposure of the slices to a high potassium medium and potential dopamine agonist drugs were added to the medium 10 min before superfusing with high potassium. A permanently charged quaternary ammonium analog and dimethylselenonium analog of dopamine inhibited the potassium-evoked release of [3H]acetylcholine, and this inhibition was antagonized by sulpiride, a dopamine receptor antagonist. However, this inhibition was not antagonized by reserpine and alpha-methyl-p-tyrosine, which was shown to completely antagonize the inhibitory effect of amphetamine, an indirectly acting amine. This suggests that the charged dopamine analogs are acting directly on dopaminergic receptors. In contrast to the permanently charged dopamine analogs, analogs of dopamine with no net positive charge produced no inhibition of the potassium-evoked [3H]acetylcholine release. These in vitro observations are in agreement with a behavioral model in which a permanently uncharged monomethylsulfide analog of dopamine was ineffective in eliciting circling behavior after its unilateral injection into the striatum of rats in which dopamine neurons were previously lesioned by the injection of 6 hydroxydopamine into the medial forebrain bundle. In contrast, under these same conditions, the intrastriatal injection of the charged quaternary ammonium or dimethylsulfonium analog of dopamine elicited intense contralateral circling. These results suggest that the charged form of a dopamine agonist molecule is required to bind to and activate the dopamine receptor regulating [3H]acetylcholine release and circling behavior. PMID- 3109429 TI - Comparison of enzymatic and pharmacological activities of lysine-49 and aspartate 49 phospholipases A2 from Agkistrodon piscivorus piscivorus snake venom. AB - The basic Lys-49 phospholipase A2 (PLA2) from Agkistrodon piscivorus piscivorus venom is homologous to the basic Asp-49 PLA2 from the same venom as well as other snake venom PLA2 enzymes. It differs, however, in several respects, most important being replacement of the previously invariant Asp-49 at the calcium binding site by Lys, resulting in a reversed order of addition of calcium and phospholipid, phospholipid binding first. Although the preferences for phospholipid substrates of the two enzymes are identical, the apparent Vmax of the Lys-49 PLA2 was only 1.4 to 3% that of the Asp-49 enzyme. Similarly, the Lys 49 PLA2, compared to the Asp-49 PLA2 had less than 3% of the intraventricular lethal potency and 4% of the anticoagulant activity. The intravenous lethal potency of the Lys-49 enzyme was 20% that of the Asp-49 PLA2 and both had little direct hemolytic activity. In contrast, both enzymes were approximately equipotent on the phrenic nerve-diaphragm preparation and on the isolated ventricle strip of the heart. On the cardiac and neuromuscular preparations, the effects of the Asp-49 PLA2 were accompanied by hydrolysis of phosphatidylcholine and phosphatidylethanolamine, whereas no phospholipid hydrolysis was observed with the Lys-49 PLA2. Evaluation of the present results, along with earlier findings using Asp-49 PLA2 enzymes from Naja nigricollis, Hemachatus haemachatus and Naja naja atra venoms, allows us to conclude that: The A. p. piscivorus Asp 49 PLA2 enzyme resembles the Asp-49 enzymes from N. n. atra and H. haemachatus. In contrast, the A. p. piscivorus Lys-49 PLA2 has much lower enzymatic and anticoagulant activities than the Asp-49 enzymes, but equal cardiotoxic and junctional effects. In contrast to some previous suggestions, basic PLA2 enzymes are not necessarily more toxic than neutral or acidic enzymes. Pharmacological effects upon the heart and phrenic nerve-diaphragm preparation correlate neither with in vitro measurements of PLA2 activity nor with actual levels of phospholipid hydrolysis in the heart or diaphragm. This suggests that PLA2 enzymes exert effects independent of phospholipid hydrolysis. PMID- 3109430 TI - Effects of different monoamine oxidase inhibitors on the metabolism of L-dopa in the rat brain. AB - The influence of monoamine oxidases A and B on the metabolism of dopamine or the expanded dopamine pool following L-dopa administration remains unclear. This study found that treatment of Sprague-Dawley rats with monoamine oxidase inhibitors strongly affected L-dopa metabolism in the brain, but the influence varied with each individual inhibitor. In animals pretreated with pargyline or clorgyline, L-dopa administration led to huge accumulations of dopamine and significantly raised central norepinephrine concentrations. In contrast, similar L-dopa injections in deprenyl-pretreated rats caused only a moderate rise in dopamine and no change in norepinephrine. There seems to be little relationship between the degree of monoamine oxidase inhibition and the accumulation of catecholamines and their metabolites in the rat brain. The effects of monoamine oxidase inhibitors on dopamine accumulation appeared to occur outside the catecholaminergic neurons since in the animals pretreated with 6-hydroxydopamine, which decreased significantly the content of brain catecholamines, dopamine accumulation following L-dopa administration still remained considerable. On the other hand, the influence of monoamine oxidase inhibitors on brain norepinephrine concentrations seemed to originate in the noradrenergic neurons because norepinephrine increase was greatly reduced in rats treated with 6 hydroxydopamine but was restored when the treatment with 6-hydroxydopamine was accompanied by desimipramine which specifically protects noradrenergic stores. PMID- 3109432 TI - Signal response transduction in rabbit neutrophil leucocytes. The effects of exogenous phospholipase A2 suggest two pathways exist. AB - Rabbit neutrophils stimulated by chemotactic peptide (fMLP) or phorbol ester (PMA) respond with a metabolic burst which can be assayed by following luminol enhanced chemiluminescence. Depending upon the agonist used, exogenous bee-venom phospholipase A2 (PLA2) will enhance or inhibit the response. Neutrophil activation by fMLP is enhanced by PLA2 or by the addition of arachidonic acid, but unaffected by lysophosphatide. The cellular response to PMA is markedly inhibited by PLA2 or by lysophosphatide, though not completely abrogated, but is enhanced by arachidonic acid. The lysophosphatide inhibition overrides the arachidonic acid potentiation of the PMA-induced response. Neither PLA2 nor arachidonic acid alone will activate the cells; it seems that agonist is essential. We interpret these results to mean that at least two signal-response transduction systems are involved in agonist-induced metabolic activation of rabbit neutrophil leucocytes. PMID- 3109431 TI - 5'-deoxy-5'-methylthioadenosine phosphorylase--IV. Biological activity of 2 fluoroadenine-substituted 5'-deoxy-5'-methylthioadenosine analogs. AB - 5'-Deoxy-5'-methylthioadenosine phosphorylase (MTAPase) phosphorolyzes 5'-deoxy 5'-methylthioadenosine (MTA) generated during polyamine biosynthesis to adenine and 5-methylthioribose-1-phosphate. Two doubly-substituted, 2-fluoroadenine containing analogs of MTA, 5'-deoxy-2-fluoroadenosine (5'-dFAdo) and 5'-deoxy-5' iodo-2-fluoroadenosine (5'-IFAdo), were synthesized and studied as substrates of MTAPase: their reaction with this enzyme resulted in the liberation of the cytotoxic base, 2-fluoroadenine, as well as potentially cytotoxic analogs of 5 methylribose-1-phosphate. The activities of these MTA analogs were compared to that of the singly-substituted analog, 5'-deoxy-5'-methylthio-2-fluoroadenosine (5'-MTFAdo). The cytotoxic action of these MTA analogs depended primarily on their conversion to 2-fluoroadenine-containing nucleotides, as a cell line that contains both MTAPase and adenine phosphoribosyltransferase (APRT) activity (HL 60 human promyelocytic leukemia) readily converted these MTA analogs to 2 fluoroadenine-containing nucleotides (especially 2-fluoroadenosine triphosphate) and was highly sensitive to the growth-inhibitory effects of all three compounds (IC50 values in the 10(-8) M range), whereas cell lines lacking MTAPase (CCRF-CEM human T-cell leukemia) or APRT (HL-60/aprt1 cells) did not form analog nucleotides and were relatively insensitive to these compounds (IC50 values in the 10(-5) M range). The doubly-substituted analogs were not more growth inhibitory than 5'-MTFAdo in wild type HL-60 cells as the potent effects of 2 fluoroadenine may mask the activity of the 5-methylthioribose-1-phosphate analogs generated in the reaction of these compounds with MTAPase. 5'-dFAdo and 5'-IFAdo also were irreversible inhibitors of S-adenosylhomocysteine hydrolase, which may explain in part the weak but observable growth inhibitory action of these compounds against MTAPase-deficient cell lines. PMID- 3109433 TI - The effect of sodium valproate on the subcellular particles of the rat liver. AB - Sodium valproate, 200 mg/kg, i.p., for three weeks produced an increase in the mean sedimentation coefficient of liver mitochondria, while no changes were observed in lysosomes and peroxisomes. As the mean density of the mitochondria, the lysosomes and the peroxisomes of the control and treated animals were not different, it was concluded that the size of the mitochondria had increased in the liver of the treated rats. The mean sedimentation coefficient of the mitochondria returned to normal after the administration of the drug was interrupted for 8 days, indicating a reversible phenomenon. The mechanical and osmotical fragility of the mitochondria and the peroxisomes were not affected by sodium valproate. The osmotic stability of the lysosomes was increased in the in vivo experimental conditions. PMID- 3109434 TI - Mechanism of selective toxicity of 4-S-cysteinylphenol and 4-S-cysteaminylphenol to melanocytes. AB - Our previous studies showed that 4-S-cysteinylphenol (4-S-CP) and 4-S cysteaminylphenol (4-S-CAP) inhibit the growth of malignant melanoma and cause depigmentation of black skin. In this study we examined kinetic constants of CP and CAP as substrates for tyrosinases and their properties as sulphydryl scavengers. 4-S-CP and 4-S-CAP were found to be much better substrates for mushroom tyrosinase than L-tyrosine while their 2-S isomers were not the substrates. 4-S-CP and 4-S-CAP were also good substrates for mammalian tyrosinase. Upon tyrosinase oxidation the two phenols conjugated with cysteine to form the cysteinyl derivatives of the corresponding catechols via o-quinone forms. The tyrosinase oxidation product of 4-S-CP had a poor ability to conjugate with alcohol dehydrogenase, a sulphydryl enzyme, while that of 4-S-CAP had a much higher ability. These results suggest that in melanocytes these phenols are oxidised by tyrosinase to the corresponding o-quinone forms, some of which conjugate with sulphydryl enzymes through cysteine residues, thus exerting cytotoxic effects. PMID- 3109435 TI - Actions of cannabis constituents on enzymes of arachidonate metabolism: anti inflammatory potential. PMID- 3109436 TI - Effects of carbon dioxide on onsets of seizures in mice induced by antagonists of vitamin B6. PMID- 3109437 TI - In vitro inhibition of rat brain protein kinase C by rhodamine 6G. Profound effects of the lipid cofactor on the inhibition of the enzyme. AB - Rhodamine 6G inhibited protein kinase C (PKC) when the enzyme was activated by Ca2+ plus phosphatidylserine, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or mezerein plus phosphatidylserine, Ca2+ plus arachidonic acid, or arachidonic acid alone. Rhodamine 6G did not affect protein kinase C activity in the absence of lipid cofactor and, thus, does not appear to inhibit the enzyme through direct interactions with the active site. The inhibitory potency of the drug was affected dramatically by the nature of the lipid cofactor. Thus, 50 microM rhodamine 6G inhibited the Ca2+ plus arachidonic acid dependent protein kinase activity approximately 50%, whereas 800 microM rhodamine 6G was required to cause 50% inhibition of the Ca2+ plus phosphatidylserine dependent protein kinase activity. These results, along with studies demonstrating a reversal of inhibition by high lipid concentrations, provide evidence that rhodamine 6G exerts its inhibitory effect on PKC through drug-lipid interactions. The dramatic effect of the lipid cofactor on the potency of rhodamine 6G as a PKC inhibitor suggests that the lipid environment of the cell may profoundly affect the abilities of rhodamine 6G and related cationic lipophilic drugs to inhibit PKC in vivo. PMID- 3109438 TI - Inhibition of human purine nucleoside phosphorylase by acyclic nucleosides and nucleotides. AB - In an effort to develop more potent inhibitors of human purine nucleoside phosphorylase (PNP) as immunosuppressive and cancer chemotherapeutic agents, the affinity of the erythrocytic enzyme for 30 acyclic nucleosides, nucleotides and related compounds was determined. Among the acyclonucleosides, 2' nordeoxyguanosine [2'NDG, 9-(1,3-dihydroxy-2-propoxymethyl)guanine] had a 3-fold greater affinity than acyclovir, and 8-amino-2'NDG was the best inhibitor with Ki = 2.6 X 10(-7) M. The ether moiety of the acyclovir and 2'NDG side-chains was not important for binding. Phosphorylated 2'NDG analogs appeared to act as multisubstrate analogs with optimal binding at low (1 mM) phosphate concentration. The 2'NDG mono- and triphosphates had higher affinities than those reported for the phosphorylated acyclovir derivatives but the diphosphate had a similar Ki value of 9 X 10(-9) M. Poor affinity, independent of phosphate concentration, was found for 9-(2-phosphonoethyl)guanine. The 3'-phosphate derivative of 8-(3-hydroxypropyl)-9-methylguanine inhibited with a Ki = 2 X 10( 5) M in 1 mM phosphate. The chemical syntheses of new analogs are described. PMID- 3109439 TI - Induction of the hepatic microsomal cytochrome P-450 system by trialkyl phosphorothioates in rats. AB - Single i.p. doses of O,O,O-triethyl phosphorothioate [OOO-Et(S)], one of the suicide substrates for cytochrome P-450, caused a rapid increase of NADPH cytochrome c reductase activity in rat liver microsomes. The increase was dose dependent but did not coincide with the recovery from the inhibition of drug metabolizing activities. There was no change of Km value of the reductase in the induced state. The co-administration of cycloheximide repressed the stimulatory effect of OOO-Et(S), suggesting that a de novo synthesis of enzyme protein may be responsible for the increase in activity. Of four homologous tri-n-alkyl esters tested, the triethyl compound was the most effective at 24 and 48 hr after administration. Triethyl phosphate, the oxygen analog of OOO-Et(S), also caused an increase of the reductase activity, but carbon disulfide had no influence on this activity. Although O,O,S-triethyl phosphorodithioate [OOS-Et(S)] and its n alkyl homologs also caused the inhibition of drug-metabolizing activities and the increase of the reductase activity, the recovery and the stimulation of enzyme activity were different from that of O,O,O-tri-n-aklyl phosphorothioates. PMID- 3109440 TI - Metabolism of alkoxyphenoxazones by channel catfish liver microsomes: effects of phenobarbital, Aroclor 1254 and 3-methylcholanthrene. PMID- 3109441 TI - Effect of ethanol feeding on hepatic microsomal UDP-glucuronyltransferase activity. PMID- 3109442 TI - [Synthesis of (8Z,11Z,14Z)-eicosatrien-5-ynoic (5,6-dehydroarachidonic) acid and its transformation into [5,6-3H]arachidonic acid and [5,6-3H]prostaglandins E2 and F2 alpha]. AB - 8Z,11Z,14Z-Eicosatriene-5-ynoic acid and its tritium-labelled analogue, [5,6 3H]arachidonic acid, have been synthesized on the basis of acetylenic compounds. [5,6-3H]Arachidonic acid has been used as substrate for the enzymatic synthesis of [5,6-3H]PGE2 and [5,6-3H]PGF2 alpha. PMID- 3109443 TI - Interleukin-1 beta and interleukin-1 alpha stimulate the plasminogen activator activity and prostaglandin E2 levels of human synovial cells. AB - Monocyte-macrophage polypeptides (monokines) cause synovial cells to increase the levels of putative mediators of destruction and inflammation. This interaction may account for some of the properties of rheumatoid pannus. We report here that samples of purified human interleukin-1 beta (IL-1 beta) and recombinant IL-1 alpha stimulate both the plasminogen activator activity and prostaglandin E2 levels of human synovial fibroblast-like cells. The same holds true for purified pig IL-1 (catabolin) and recombinant murine IL-1. The elevation in plasminogen activator activity was inhibited by indomethacin, and this suggests that endogenous prostanoids are important in the IL-1-mediated stimulation of proteinase activity. PMID- 3109444 TI - Activation of complement and coagulation in juvenile dermatomyositis. AB - In patients with juvenile dermatomyositis (JDM), small vessel occlusion and thrombosis result in a decrease in the capillary: muscle fiber ratio. We studied 15 patients with JDM. Six of 7 patients with clinically active JDM had elevated levels of C3d. Moreover, concentrations of fibrinopeptide A and factor VIII related antigen were significantly increased in patients with clinically active JDM. PMID- 3109446 TI - Polar lipids of thermophilic prokaryotic organisms: chemical and physical structure. PMID- 3109445 TI - Fish oil in angina pectoris. AB - The effect of 12 weeks supplementation with fish oil on the number of anginal attacks and consumption of glyceryltrinitrate in 36 patients with stable angina pectoris was evaluated in a clinically controlled trial using a vegetable oil as placebo. Fish oil caused a decrease in frequency of angina, but was not significantly superior to placebo. However, due to the small sample size and a high spontaneous variation in number of anginal attacks, a risk of up to 50% of overlooking a 30% reduction in anginal attacks could be estimated. A significant inhibition of the epinephrine-induced platelet aggregation and a significant increase in intraplatelet cyclic AMP were induced by fish oil. PMID- 3109447 TI - Structural studies of halophilic proteins, ribosomes, and organelles of bacteria adapted to extreme salt concentrations. PMID- 3109448 TI - [Delayed cutaneous hypersensitivity reactions in neurofibromatosis patients]. PMID- 3109449 TI - Hyperventilation and anxiety: alcohol withdrawal symptoms decreasing with prolonged abstinence. AB - We previously presented evidence that hyperventilatory and anxiety symptoms are the result of physically dependent alcohol use rather than a premorbid condition. The purpose of the present study was to examine the effect of prolonged abstinence versus resumption of dependent drinking on those symptoms. Two questionnaires (a hyperventilation complaint checklist and Spielberger's Anxiety Inventory) were presented twice to 15 ss, once during an inpatient treatment and once after a median followup period of 17 months. Six ss were abstinent for the entire period, 3 were abstinent with 1 or 2 slips and 6 ss were drinking in a dependent way again for at least 6 months. In the abstinent or abstinent-with slips group, a significant decrease over time in hyperventilatory symptoms and trait (but not state) anxiety could be found, whereas in the dependent drinking group there was a significant increase in hyperventilatory symptoms and state (but not trait) anxiety. An extended followup in 5 abstinent ss showed a continued decrease in those symptoms. These results provide further evidence for the hypothesis that hyperventilation and anxiety are part of a subacute alcohol withdrawal syndrome. PMID- 3109450 TI - Crystalline NAD/NADP-dependent malate dehydrogenase; the enzyme from the thermoacidophilic archaebacterium Sulfolobus acidocaldarius. AB - Malate dehydrogenase from Sulfolobus acidocaldarius has been purified 240-fold to apparent electrophoretic homogeneity. The enzyme shows a specific activity of 277 U/mg and crystallizes readily. The relative molecular mass of the native enzyme is estimated as 128,500 by ultracentrifugation. After cross-linking a relative molecular mass of 134,000 is found by sodium dodecyl sulfate gel electrophoresis. Malate dehydrogenase from S. acidocaldarius is composed of four subunits of identical size with a relative molecular mass of 34,000. Active-enzyme sedimentation in the analytical ultracentrifuge indicates that the tetramer is the catalytically active species. Kinetic studies in the direction of oxaloacetate reduction showed a Km for NADH of 4.1 microM and a Km for oxaloacetate of 52 microM. Oxaloacetate exhibits substrate inhibition at higher concentrations, L-malate, NAD and NADP were found to be product inhibitors. The enzymatic activity is inhibited by 2-oxoglutarate but not by the adenosine nucleotides AMP, ADP and ATP. Only low activity is detected in the direction of malate oxidation. Malate dehydrogenase from S. acidocaldarius utilizes both NADH and NADPH to reduce oxaloacetate. The enzyme shows A-side stereospecificity for both nicotinamide dinucleotides. PMID- 3109451 TI - Proliferation-dependent changes of proteoglycan metabolism in arterial smooth muscle cells. AB - Cultured arterial smooth muscle cells synthesize and secrete two types of sulfated proteoglycans designated as proteoglycan A and proteoglycan B. Proteoglycan A has been characterized as chondroitin sulfate-rich, whereas proteoglycan B was found to be dermatan sulfate-rich [Schmidt, A. & Buddecke, E. (1985) Eur. J. Biochem. 153, 260-273]. During the logarithmic growth phase, arterial smooth muscle cells incorporated about 3 times more [35S]sulfate into the total proteoglycans secreted into the culture medium than did non-dividing cells. When arterial smooth muscle cells stopped proliferating the ratio of [35S]proteoglycan A/B increased. No differences were detected in the respective molecular and chemical characteristics of purified proteoglycans A and B isolated from both proliferating and non-dividing cells. Regardless of the growth phase proteoglycan A had a molecular mass of about 280 kDa and contained 8-9 chondroitin sulfate-rich side chains. Proteoglycan B had a molecular mass of about 180 kDa and contained 6-7 dermatan sulfate-rich side chains. The [35S]methionine-labelled protein cores of proteoglycan A and B had a molecular mass of about 48 kDa, but were distinguishable by their specific reactions to monospecific antibodies. Proliferating cells endocytosed proteoglycan B at a rate up to 100% higher than that of non-dividing cells. In all growth phases proteoglycan A was endocytosed at a 10-fold lower rate than proteoglycan B. PMID- 3109452 TI - [Platelet aggregation induced by arachidonic acid, ADP, thrombin. Study of the antiaggregation effects of verbenone and indomethacin]. PMID- 3109453 TI - Ritanserin (R 55667) an original thymosthenic. PMID- 3109454 TI - Transgenic mice with immunoglobulin genes. PMID- 3109455 TI - The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. PMID- 3109456 TI - Early events in T-cell maturation. PMID- 3109457 TI - The structure of the CD4 and CD8 genes. PMID- 3109458 TI - Radiation therapy of hemangiomas, 1909-1959. A cohort based on 50 years of clinical practice at Radiumhemmet, Stockholm. AB - Radium and roentgen therapies for hemangiomas of the skin (mainly strawberry hemangiomas) were used between 1909 and 1959 at Radiumhemmet, Stockholm. The total number of admitted patients with hemangioma of the skin during this period was 20,012. About 90 per cent were treated with irradiation and radium therapy was the most commonly used modality. Needles, tubes and flat applicators containing radium were used. Roentgen therapy was given by using standard machines available at the time. A small number of patients were treated with 32P plaques. Most hemangiomas were located in the head-neck region (47%) and 30 per cent were located on the thorax and upper part of the abdomen. The median age at the first treatment was 6 months and 99 per cent of all patients were younger than 2 years of age at the time of treatment. The purpose of the investigation was to define a cohort, useful for studies on possible late effects following exposure to ionizing radiation in childhood. PMID- 3109459 TI - Calculation and application of point spread functions for treatment planning with high energy photon beams. AB - A general dose calculation method for treatment planning with high energy photon beams, based on folding of the total energy released by primary photons per unit mass, the terma, with a fractional mean energy imparted point spread function is described. A set of point spread functions has been calculated with Monte Carlo technique for energies of primary photons between 100 keV and 20 MeV. Dose distributions have been calculated for a 6 MV bean using the method. The results clearly point out the considerably increased precision and flexibility achieved when calculating photon beam dose distributions from first principles using Monte Carlo generated point spread functions. The point spread functions calculated in this work are available on magnetic tape from the authors. PMID- 3109460 TI - The decline of long-term prescribing to opioid users in the United Kingdom. PMID- 3109461 TI - Pharmacokinetics of intravenous and oral sodium 2-mercaptoethane sulphonate (mesna) in normal subjects. AB - The pharmacokinetics of mesna (sodium 2-mercaptoethane sulphonate) and its inactive disulphide, dimesna, were investigated using high performance liquid chromatography in six normal subjects following intravenous and oral administration of 800 mg mesna. The mean maximum mesna concentration after i.v. administration was 111 (s.d. +/- 28.3) nmol ml-1 and the mean maximum dimesna concentration was 183 (s.d. +/- 41.6) nmol ml-1. Following oral mesna dosing the mean peak mesna concentration was 19.6 (s.d. +/- 10.2) nmol ml-1 but mesna was only found in the plasma of five of the six subjects. The mean peak dimesna concentration was 22.5 (s.d. +/- 12.4) nmol ml-1. Following i.v. mesna administration, the mean half-life of mesna was 21.8 (s.d. +/- 3.1) min and total body clearance 1.23 (s.d. +/- 0.31) l kg-1 h-1. The mean half-life of dimesna was 1.17 (s.d. +/- 0.32) h. It was not possible to determine their half-lives after oral mesna administration. The mean mesna concentration in the 0-4 h urine collection was 9.6 (s.d. +/- 10.7; range 1.4-28.7) nmol ml-1 following i.v. mesna injection. After oral mesna the highest mesna concentration occurred in either the 0-4 or 4-8 h urine collections. The mean peak mesna concentration was 2.5 (s.d. +/- 1.7) mumol ml-1 (c.f. estimated uroprotective concentration of 1.7 mumol ml-1). The mean 4 h urinary clearance of the uroprotective species mesna was 0.413 (s.d. +/- 0.136) l kg-1 h-1. After both i.v. and oral mesna the urinary excretion of mesna is predominantly during the first 4 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109462 TI - Humoral and cellular immunity in children with active and quiescent atopic dermatitis. AB - Serum immunoglobulins (IgG, IgM, IgA and IgE), C3, and C4, T lymphocyte subsets, neutrophil chemotaxis and natural killer cell-mediated cytotoxic activity were measured in 34 children with atopic dermatitis and 31 healthy controls. Twenty four patients were re-evaluated when their dermatitis was quiescent. Serum levels of IgG, IgM and IgE were significantly higher in the patients with atopic dermatitis than in the controls, while levels of serum IgA did not differ significantly between the two groups. C3 levels were lower in the patients than in the controls and correlated inversely with clinical disease severity. C4 levels were not significantly altered. Numbers of suppressor/cytotoxic T lymphocytes and polymorphonuclear leukocyte chemotaxis were significantly reduced in the atopic patients. There was a significant inverse correlation between the natural killer cell-mediated cytotoxic activity and the severity and extent of the dermatitis. These results support the hypothesis that atopic dermatitis is connected with a defect in cellular immunity. PMID- 3109463 TI - Pattern of fibrinolytic parameters in patients with gastrointestinal carcinomas. AB - Changes in the plasma levels of components of the fibrinolytic system have been investigated in 80 patients suffering from gastrointestinal carcinomas. Urokinase antigen (RIA), tissue-type plasminogen activator antigen (ELISA) and plasminogen activator inhibitor (functional assay) were determined. Patients with pancreatic and colorectal carcinoma and metastases as well as those without metastases revealed significantly increased plasma urokinase levels. Those with gall bladder or gastric carcinoma did not show significantly elevated urokinase antigen levels compared to age-matched controls. Determination of tissue-type plasminogen activator antigen in all four carcinoma groups did not reveal significant differences when compared to an age-matched healthy control group. The concentrations of plasminogen activator inhibitor were significantly increased in all carcinoma groups; there being no differences between the patient groups with or without metastases. No correlations between the different parameters of the fibrinolytic system could be obtained. PMID- 3109465 TI - Strong inhibitory effect of furanoses and sugar lactones on beta-galactosidase Escherichia coli. AB - Various sugars and their lactones were tested for their inhibition of beta galactosidase (Escherichia coli). L-Ribose, which in the furanose form has a hydroxyl configuration similar to that of D-galactose at positions equivalent to the 3- and 4-positions of D-galactose, was a very strong inhibitor, and D-lyxose, which in the furanose form also resembles D-galactose, was a much better inhibitor than expected. Structural comparisons prelude the pyranose forms of these sugars from being significant contributors to the inhibition, and inhibition at different temperatures (at which there are different furanose concentrations) strongly supported the conclusion that the furanose form is inhibitory. Studies with sugar derivatives that can only be in the furanose form also supported the conclusion. This is the first report of the inhibitory effect of furanose on beta-galactosidase. Lactones were also inhibitory. Every lactone tested was much more inhibitory than was its parent sugar. D-Galactonolactone was especially good. Experiments indicated that it was D-galactono-1,5-lactone rather than D-galactono-1,4-lactone which was inhibitory. Inhibition of beta galactosidases from mammalian sources by lactones has been reported previously, but this is the first report of the effect of beta-galactosidase from E. coli. Since furanoses in the envelope form are analogous (in some ways) to half-chair or sofa conformations and since lactones with six-membered rings probably have half-chair or sofa conformations, the results indicate that beta-galactosidase probably destabilizes its substrate into a planar conformation of some type and that the galactose in the transition state may, therefore, also be quite planar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109464 TI - Differential oxidation of saturated and unsaturated fatty acids in vivo in the rat. AB - The oxidation rates of lauric, myristic, palmitic, stearic, oleic, alpha linolenic, linoleic, kappa-linolenic, dihomo-gamma-linolenic and arachidonic acids were studied by use of a radioisotope tracer technique in weanling rats at rest in a metabolism chamber over 24 h. Of the saturated fatty acids, lauric acid (12:0) was the most efficient energy substrate: the longer the chain length of the saturated fatty acids, the slower the rate of oxidation. Oleic acid (18:1) was oxidized at a remarkably fast rate, similar to that of lauric acid. Of the omega 6 essential fatty acids studied, linoleic acid (18:2 omega 6) was oxidized at a faster rate than any of its metabolites, with arachidonic acid (20:4 omega 6) being oxidized at the slowest rate. The rate of oxidation of gamma-linolenic acid (18:3 omega 3) was almost as fast as that of lauric and oleic acids. PMID- 3109467 TI - Purification of bleomycin hydrolase with a monoclonal antibody and its characterization. AB - We established a hybridoma clone that produced anti-bleomycin hydrolase antibody. The subclass of the monoclonal antibody was immunoglobulin M. The antibody significantly reacted with bleomycin hydrolase from rabbit tissues, mouse livers, sarcoma 180, and adenocarcinoma 755 but not significantly with that from MH 134 and Ehrlich carcinoma. The enzyme from L5178Y cells showed an intermediate reactivity. Bleomycin hydrolase was purified from rabbit liver by immunoaffinity with the monoclonal antibody and DEAE gel chromatography. Approximately 1300-fold purified bleomycin hydrolase was obtained. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing on a polyacrylamide slab gel of purified bleomycin hydrolase showed a single band with an apparent Mr of 48K and an isoelectric pH of 5.2. The molecular weight of bleomycin hydrolase determined on gel filtration high-performance liquid chromatography was ca. 300K, suggesting a hexameric enzyme. The enzyme showed an optimum pH of 6.8-7.8 and gave a Vmax value of 6.72 mg min-1 mg-1 for peplomycin and 9.24 mg min-1 mg-1 for bleomycin B2 and a Km value of 0.79 mM for both substrates. The enzyme was inhibited by E 64, leupeptin, p-tosyl-L-lysine chloromethyl ketone, N-ethylmaleimide, Fe2+, Cu2+, and Zn2+ but was enhanced by dithiothreitol. The results suggest that bleomycin hydrolase is a thiol enzyme. PMID- 3109466 TI - Transcriptional and posttranscriptional effects of dexamethasone on albumin and procollagen messenger RNAs in murine schistosomiasis. AB - We have previously shown that dexamethasone increases albumin mRNA and decreases procollagen steady-state mRNA levels in rat hepatocyte cultures. These studies were extended by evaluating an in vivo model of fibrogenesis (murine schistosomiasis) and by determining a more precise level of gene expression responsible for these changes. Control mice and litter mates infected with Schistosomiasis mansoni were evaluated at 8 weeks postinfection when the livers of the infected mice had become fibrotic and their serum albumin levels significantly decreased. The addition of 4 micrograms/mL dexamethasone to the drinking water of half of the infected mice led to a 75% decrease in the liver collagen content as determined by high-performance liquid chromatography. RNA was extracted from the livers of mice under three conditions: control and infected +/ dexamethasone. This RNA was then hybridized with cDNA probes to determine steady state levels of specific mRNAs. In the infected mice, albumin mRNA levels were decreased compared to control; however, infected mice treated with dexamethasone increased their albumin mRNA content by 3-fold at 8 weeks. Types I and IV procollagen steady-state mRNA levels in infected mice were increased compared to control while dexamethasone suppressed the mRNA level of collagen in infected mice by 50%. The level of gene expression responsible for these steady-state changes was evaluated by nuclear run-on analysis. While the effect of schistosomiasis on these genes was primarily at a transcriptional level, dexamethasone exerted its effect on different genes in the injured liver by diverse mechanisms, i.e., decreasing collagen synthesis at a transcriptional level and increasing albumin by posttranscriptional mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109468 TI - 500-MHz proton homonuclear Overhauser evidence for additional base pair in the common arm of eukaryotic ribosomal 5S RNA: wheat germ. AB - A "common-arm" fragment from wheat germ (Triticum aestivum) 5S RNA has been produced by enzymatic cleavage with RNase T1 and sequenced via autoradiography of electrophoresis gels for the end-labeled fragments obtained by further RNase T1 partial digestion. The existence, base pair composition, and base pair sequence of the common arm are demonstrated for the first time by means of proton 500-MHz nuclear magnetic resonance. From Mg2+ titration, temperature variation, ring current calculations, sequence comparisons, and proton homonuclear Overhauser enhancement experiments, additional base pairs in the common arm of the eukaryotic 5S RNA secondary structure are detected. Two base pairs, G41 X C34 and A42 X U33 in the hairpin loop, could account for the lack of binding between the conserved GAAC segment of 5S RNA and the conserved Watson-Crick-complementary GT psi C segment of tRNAs. PMID- 3109469 TI - Ribosome protection by tRNA derivatives against inactivation by virginiamycin M: evidence for two types of interaction of tRNA with the donor site of peptidyl transferase. AB - Virginiamycin M (VM) was previously shown to interfere with the function of both the A and P sites of ribosomes and to inactivate tRNA-free ribosomes but not particles bearing peptidyl-tRNA. To explain these findings, the shielding ability afforded by tRNA derivatives positioned at the A and P sites against VM-produced inactivation was explored. Unacylated tRNA(Phe) was ineffective, irrespective of its position on the ribosome. Phe-tRNA and Ac-Phe-tRNA provided little protection when bound directly to the P site but were active when present at the A site. Protection by these tRNA derivatives was markedly enhanced by the formation of the first peptide bond and increased further upon elongation of peptide chains. Most of the shielding ability of Ac-Phe-tRNA and Phe-tRNA positioned at the A site was conserved when these tRNAs were translocated to the P site by the action of elongation factor G and GTP. Thus, a 5-10-fold difference in the protection afforded by these tRNAs was observed, depending on their mode of entry to the P site. This indicates the occurrence of two types of interaction of tRNA derivatives with the donor site of peptidyl transferase: one shared by acylated tRNAs directly bound to the ribosomal P site (no protection against VM) and the other characteristic of aminoacyl- or peptidyl-tRNA translocated from the A site (protection of peptidyl transferase against VM). To explain these data and previous observations with other protein synthesis inhibitors, a new model of peptidyl transferase is proposed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109470 TI - Chemical modification of bovine transducin: effect of fluorescein 5' isothiocyanate labeling on activities of the transducin alpha subunit. AB - Fluorescein 5'-isothiocyanate (FITC) was used to modify the lysine residues of bovine transducin (T), a GTP-binding protein involved in phototransduction of rod photoreceptor cells. The incorporation of FITC showed a stoichiometry of approximately 1 mol of FITC/mol of transducin. The labeling was specific for the T alpha subunit. There was no significant incorporation on the T beta gamma subunit. The modification had no effect on the transducin-rhodopsin interaction or on the binding of guanosine 5'-(beta, gamma-imidotriphosphate) [Gpp(NH)p] to transducin in the presence of photolyzed rhodopsin. The dissociation of the FITC transducin-Gpp(NH)p complex from rhodopsin membrane remained unchanged. However, the intrinsic GTPase activity of T alpha and its ability to activate the cGMP phosphodiesterase were diminished by FITC modification. The rate of FITC labeling of the transducin-Gpp(NH)p complex was about 3-fold slower than that of transducin. Limited tryptic digestion and peptide mapping were used to localize the FITC labeling site. The majority of the FITC label was on the 23-kilodalton fragment, and a minor amount was on the 9-kilodalton fragment of the T alpha subunit. These results indicate that FITC labeling does not alter the activation of transducin by photolyzed rhodopsin but does affect the GTP hydrolytic activity as well as the GTP-induced conformational change of T alpha, which ultimately leads to the activation of cGMP phosphodiesterase. PMID- 3109472 TI - Tryptophan fluorescence studies of subunit interaction and rotational dynamics of human luteinizing hormone. AB - Human luteinizing hormone (hLH) has a single tryptophan residue occurring in the beta-subunit (beta hLH). This provides an intrinsic fluorescent probe, in native hLH and beta hLH, that is unambiguously assigned. The fluorescence intensities of hLH and beta hLH are, however, significantly different. This difference has been utilized in studying the interaction of fluorescent beta hLH with the nonfluorescent alpha-subunit. The accessibility of the tryptophan residue in native hLH and beta hLH has been assessed by measuring the rate of collisional fluorescence quenching and by solvent perturbation (D2O/H2O) of fluorescence. Fluorescence anisotropy measurements have been used in studying the intramolecular dynamics and segmental tryptophan mobility in hLH and beta hLH. Lifetime-resolved anisotropy, measured by the technique of oxygen quenching of fluorescence, has revealed the presence of segmental tryptophan motion. These data can be satisfactorily explained in terms of fast segmental tryptophan motion and rotational diffusion of the whole protein and do not require that intersubunit motion be invoked for intact hLH as it was suggested earlier on the basis of fluorescence depolarization of fluorescein-labeled hLH [Bishop, W. H., & Ryan, R. J. (1975) Biochem. Biophys. Res. Commun. 65, 1184-1190]. PMID- 3109471 TI - Production of antibodies against rhodopsin after immunization with beta gamma subunits of transducin: evidence for interaction of beta gamma-subunits of guanosine 5'-triphosphate binding proteins with receptor. AB - The light-detecting system of retinal rod outer segments is regulated by a guanyl nucleotide binding (G) protein, transducin, which is composed of alpha-, beta-, and gamma-subunits. Transducin couples rhodopsin to the intracellular effector enzyme, a cGMP phosphodiesterase. The beta gamma complex (T beta gamma) is required for the alpha-subunit (T alpha) to interact effectively with the photon receptor rhodopsin. It is not clear, however, whether T beta gamma binds directly to rhodopsin or promotes T alpha binding to rhodopsin only by binding to T alpha. We have found that serum from rabbits immunized with T beta gamma contained a population of antibodies that were reactive against rhodopsin. These antibodies could be separated from T beta gamma antibodies by absorbing the latter on immobilized transducin. Binding of purified rhodopsin antibodies was inhibited by T beta gamma, suggesting that the rhodopsin antibodies and T beta gamma bound to the same site on rhodopsin. We propose that the rhodopsin antibodies act both as antiidiotypic antibodies against the idiotypic T beta gamma antibodies and as antibodies against rhodopsin. This hypothesis is consistent with the conclusion that T beta gamma interacts directly with the receptor. It is probable that in an analogous way, G beta gamma interacts directly with receptors of the adenylate cyclase system. PMID- 3109473 TI - Role of amino-terminal residues in the folding of the constant fragment of the immunoglobulin light chain. AB - Three constant fragments with different amino terminals, CL(105-214), CL(109 214), and CL(113-214), were obtained by limited proteolysis with trypsin or papain of a type lambda immunoglobulin light chain. The conformations of the three CL fragments were indistinguishable on the basis of circular dichroism and tryptophyl fluorescence spectra. The stability to heat and guanidine hydrochloride of CL(105-214) was almost the same as that of CL(109-214), but the stability of CL(113-214) was slightly lower than that of CL(105-214) or CL(109 214). The midpoint of the thermal unfolding transition at pH 7.5 was at 60.0 degrees C for CL(105-214), 60.4 degrees C for CL(109-214), and 57.5 degrees C for CL(113-214). The midpoint of the unfolding transition by guanidine hydrochloride at pH 7.5 and 25 degrees C was 1.2 M for CL(105-214) and CL(109-214) and at 1.0 M for CL(113-214). The kinetics of unfolding and refolding by guanidine hydrochloride of these CL fragments were analyzed on the basis of the three species mechanism, U1 in equilibrium with U2 in equilibrium with N, where U1 and U2 are the slow-folding and fast-folding species, respectively, of unfolded protein and N is native protein. It was found that only the microscopic unfolding rate constant for CL(113-214) is 2-3 times greater than that for CL(105-214) or CL(109-214) and that the other microscopic rate constants for the three CL fragments are all the same. These findings indicated that the amino-terminal residues, Gly-109-Lys-112, or a part of them, stabilize the CL(113-214) fragment by decreasing only the unfolding rate, that the transition state of the folding of the CL fragment is independent of the presence or absence of this peptide, and that, at the last step of folding, the peptide is incorporated into the globular domain, thus stabilizing it. PMID- 3109474 TI - Purification and properties of a very high density lipoprotein from the hemolymph of the honeybee Apis mellifera. AB - A larval-specific very high density lipoprotein (VHDL) has been isolated from the hemolymph of the honeybee Apis mellifera. VHDL was isolated by a combination of density gradient ultracentrifugation and gel filtration. The purified protein is a dimer of Mr 160,000 apoproteins as shown by chemical cross-linking with dimethyl suberimidate. N-Terminal sequence analysis indicates that the two polypeptide chains are identical. The holoprotein contains 10% lipid by weight and 2.6% covalently bound carbohydrate. A native Mr 330,000 species was obtained by gel permeation chromatography. Antiserum directed against VHDL was used to show that VHDL is distinct from other hemolymph proteins and appears to constitute a novel lipoprotein of unknown function. However, the lipoprotein is present in high amounts in hemolymph only at the end of larval life, suggesting a potential role in lipid transport and/or storage protein metabolism during metamorphosis. PMID- 3109475 TI - Covalent coupling of the variable loop of the elongator methionine tRNA to a specific lysine residue in Escherichia coli methionyl-tRNA synthetase. AB - A lysine-reactive cross-linker has been coupled to the minor base 3-(3-amino-3 carboxypropyl)uridine in the variable loop of the Escherichia coli elongator methionine tRNA (tRNA(mMet]. Incubation of the derivatized tRNA with E. coli methionyl-tRNA synthetase (MetRS) resulted in covalent coupling of the protein and nucleic acid and loss of amino acid acceptor activity of the enzyme. One mole of tRNA was cross-linked per mole of enzyme inactivated. Enzyme activity was largely restored by release of the bound tRNA following cleavage of the disulfide bond in the cross-linker with a sulfhydryl reagent. The cross-linking reaction was effectively inhibited by unmodified tRNA(mMet) but not by noncognate tRNA(Phe). The covalent complex was digested with trypsin, and the resulting tRNA bound peptides were isolated by anion-exchange chromatography. The cross-linked peptides were released from the tRNA by cleavage in the disulfide bond of the cross-linker and purified by reverse-phase high-pressure liquid chromatography, yielding one major peptide plus several minor peptides. Amino acid analysis indicated that the major product was an octadecapeptide cross-linked to tRNA(mMet) through lysine residue 596 in the primary sequence of MetRS. The N terminal sequence of the peptide was determined to be Val-Ala-Leu-Ile-Glu-Asn-Ala Glu-Phe-Val, corresponding to residues 582-591 in MetRS. The procedures described here should be applicable to the determination of peptide sequences near the variable loop of other tRNAs containing the 3-(3-amino-3-carboxypropyl)uracil base when such tRNAs are bound to specific proteins. PMID- 3109477 TI - Induction, by adriamycin and mitomycin C, of modifications in lipid composition, size distribution, membrane fluidity and permeability of cultured RDM4 lymphoma cells. AB - Adriamycin and mitomycin C were previously found to modulate the sensitivity of lymphoma cells to lysis by certain effectors of immunity and this modulation was dependent on drug concentration. In the present studies, RDM4 lymphoma cells were treated with different concentrations of the two drugs for 24 h in culture. These treatments resulted in changes in the lipid composition, membrane fluidity, cell size distribution, and permeability to 51CrO4, Trypan blue, Acridine orange and trimethylaminodiphenylhexatriene (TMA-DPH) of the cells. Changes in some of these parameters, as a function of drug concentration, resulted in dose-response curves which were bell-like shaped, hence paradoxical similarities between non-drug treated cells and cells treated with higher drug concentrations were observed. PMID- 3109476 TI - Reaction of acid-activated mitomycin C with calf thymus DNA and model guanines: elucidation of the base-catalyzed degradation of N7-alkylguanine nucleosides. AB - Mitomycin C (MC, 1) forms covalent adducts under acidic activating conditions (pH approximately 4) with deoxyguanosine, d(GpC), and guanine residues of calf thymus DNA. In the case of deoxyguanosine, five adducts arise from a common precursor, N7-(2'' beta, 7''-diaminomitosen-1''-yl)-2'-deoxyguanosine (10a; not isolated), which hydrolyzes spontaneously via two pathways: scission of the glycosidic bond to form N7-(2'' beta, 7''-diaminomitosen-1'' alpha-yl)guanine (5) and its 1'' beta-isomer (6) and imidazolium ring opening to generate three 2,6-diamino-4 hydroxy-5-(N-formyl-2'' beta, 7''-diaminomitosen-1'' beta-yl)pyrimidine (FAPyr) derivatives that are substituted at N6 by isomeric 2'-deoxyribose units [i.e., 1' beta-furanose (7), 1' alpha-furanose (8), and 1' beta-pyranose (9)]. The structures of 5-9 were determined by spectroscopic methods. The same five adducts were obtained from d(GpC), but only the guanine adducts 5 and 6 were formed in DNA. Adducts 7-9 interconvert during high-performance liquid chromatography (HPLC). The unexpected isomerization of the deoxyribose moiety of the initially formed 1' beta-furanose adduct 7 to those of 8 and 9 occurs upon imidazolium ring opening, as discerned by the course of imidazolium cleavage of the simple models N7-ethyl- and N7-methylguanosine and N7-methyl-2'-deoxyguanosine. All ring-opened N7-alkylguanosine derivatives studied here exist as a mixture of distinct N formyl rotamers, manifested by multiple interconverting peaks on HPLC and in the 1H NMR spectra. In the UV spectra of such derivatives, a new and diagnostic maximum at 218 nm (at pH 7) is observed. Acid-activated MC is found to alkylate preferentially the Gua-N7 position in deoxyguanosine or d(GpC), in contrast to reductively activated MC, which preferentially alkylates the Gua-N2 position. This finding is explained by the different electronic structures of acid- and reduction-activated MC. In DNA, the N7 specificity of acid-activated MC is partially offset by steric factors. PMID- 3109478 TI - Nuclear magnetic resonance spectra of lipoteichoic acid. AB - Lipoteichoic acid acids with a range of chemical compositions have been studied using 1H; 13C- and 31P-nuclear magnetic resonance. Proton spectroscopy provided a rapid method for demonstrating whether alanine in a sample is covalently bound to the polyglycerophosphate chains and for monitoring hydrolysis of alanine. The nature of sugar substituents can be determined, with some limitations, from the 13C spectra, and the proportions of glycerol residues substituted by alanine and sugar can be measured. The 31P spectra of lipoteichoic acid provided information about both the degree of substitution and the distribution of the substituent along the polyglycerophosphate chain, except when the substituent was galactose. The polyglycerophosphate chains were shown to undergo rapid internal rotation and no evidence for tertiary structure was found either in the presence or absence of magnesium ions. Magnesium ions exchange rapidly between the bound and free state and the binding constant to lipoteichoic acid of 64 M-1 is typical for monophosphates in aqueous solution. There was no evidence that alanine substitution affects the binding constant for magnesium ions. PMID- 3109479 TI - Characteristics of lysine transport by isolated rat renal cortical tubule fragments. AB - The uptake of L-lysine was examined in isolated renal cortical tubules. Lysine was actively taken up by the renal tubule cells isolated from 7-week-old rats. No metabolism of the transported lysine was found. There was no evidence for sodium dependence of lysine uptake. Concentration dependence studies revealed that the lysine was taken up by one saturable transport system with a Km of 1.66 mmol/l and Vmax of 7 mmol/l intracellular fluid per 10 min. Lysine also entered by a non saturable pathway. Arginine and ornithine inhibited the initial uptake of lysine. Cystine increased the efflux of lysine from preloaded renal cells via hetero exchange, indicating that a common system exists for these two amino acids. PMID- 3109480 TI - The cholecystokinin-induced Ca2+ shuttle from the inositol trisphosphate sensitive and ATP-dependent pool, and initial pepsinogen release connected with cytoskeleton of the chief cell. AB - In guinea pig chief cells, inositol 1,4,5-trisphosphate (IP3) caused release of Ca2+, which was accumulated by ATP, from an endoplasmic reticulum-enriched fraction in both the permeable system and the cell-free system. This was mimicked with the Ca2+ ionophores A23187 and ionomycin on a large scale since an IP3 sensitive Ca2+ pool might be a subset of the Ca2+ ionophore-sensitive Ca2+ pool. The permeable chief cells, but not the cell-free system, retained the ability to react to synthetic cholecystokinin octapeptide (CCK-OP) with Ca2+ release from an IP3-sensitive pool due to of the non-additive but constant effect in exerting Ca2+ release from the store(s) induced by the combination with IP3 and CCK-OP. The increase in the cytosolic free Ca2+ concentration of intact chief cells responding to CCK-OP or the Ca2+ ionophore, ionomycin, comprised two components, namely, that by the Ca2+ entry from the extracellular space, and that by the Ca2+ release from the intracellular space(s) (as measured by fura-2). When CCK-OP or ionomycin was added, there was a biphasic response of pepsinogen secretion. An initial but transient response reaching a peak in 5 min was followed by a sustained response reaching a peak in 30 min. The initial pepsinogen release was independent of medium Ca2+, whereas the sustained one was dependent on medium Ca2+. The results suggest that the intracellular Ca2+ release from the store(s), presumably endoplasmic reticulum, may trigger the initial pepsinogen release, whereas the sustained pepsinogen secretion may be caused by acting in concert with the initial response and external Ca2+ entry. On the other hand, the disruption of the microtubular-microfilamentous system by colchicine or cytochalasin D failed to cause the Ca2+ release evoked by either IP3, CCK-OP or Ca2+ ionophores and to cause the CCK-OP- or ionomycin-induced initial pepsinogen release. These findings suggest that the IP3-sensitive pool is the same Ca2+ store which is completely or partially sensitive to CCK-OP and Ca2+ ionophores, respectively, and that the assembly of the cytoskeletal system is involved in initial intracellular Ca2+ metabolism and the following initial pepsinogen release. The assembly of the cytoskeletal system may be an early event in mediating the CCK-OP-induced initial pepsinogen release, perhaps by causing the Ca2+ release from an IP3-sensitive pool of the chief cell. The translocation or attachment of the IP3-sensitive pool brought about by cytoskeletal system might be necessary to cause Ca2+ release after the cell stimulation with CCK-OP. PMID- 3109481 TI - Comparison of 59Fe3+ uptake in vitro and in vivo by mouse duodenum. AB - Initial rates of 59Fe3+ uptake by mouse duodenal fragments (in vitro) and tied off duodenal segments (in vivo) have been characterised for control and hypoxic animals. 59Fe3+ uptake by duodenal fragments was rapid, selective and dependent on medium Fe3+-nitrilotriacetate concentration. Most of the 59Fe3+ uptake (70 75%) occurred via the mucosal route and was dependent on the metabolic state of the tissue. Mucosal uptake showed an adaptive increase following exposure of animals to 3 days hypoxia; the enhancement was due to a 2-3-fold increase in Vmax app, without any significant changes in the Km app. Studies of upper small intestine transit times showed a mean residence time of 4-5 min for 59Fe-labelled mouse chow, emphasising the importance of initial uptake measurements. Time courses for in vivo total mucosal uptake exhibited linearity over a wide variety of absorption rates after correction for the permeation by intact metal-chelate complex. The corrected uptake showed a hyperbolic dependence on medium Fe3+ nitrilotriacetate concentration. Kinetic studies revealed a 2-3-fold increase in total mucosal uptake in hypoxia. Mucosa-to-carcass transfer of 59Fe was also markedly increased by chronic hypoxia. The in vitro system exhibits similar qualitative and quantitative kinetics for Fe3+ transport via the mucosal membrane to those obtained in vivo. The results observed in vitro are thus valid and provide a convenient method for further studies on Fe3+ transport in animals and in man. PMID- 3109482 TI - Isolation of purified brush-border membranes from rat jejunum containing a Ca2+ independent phospholipase A2 activity. AB - A novel phospholipase activity was recognized in intact, rat jejunal brush-border membranes and its effect on membrane lipid composition was evaluated following various incubation protocols. Brush-border membranes were isolated from mucosal scrapings by a combination of existing techniques. A brush-border plus nuclei fraction was first prepared by homogenization and low-speed centrifugation in isotonic mannitol, in the presence of 5 mM EDTA. Brush-border membrane vesicles were isolated from this fraction by homogenization, followed by precipitation of the remaining undesired membranes with 10 mM CaCl2. Membranes were judged to be highly purified by marker enzyme content, protein profile, and electron microscopy. In total lipid extracts, prepared immediately following membrane isolation, the ethanolamine phosphatides were found to be the major phospholipid class, accounting for nearly 45% of the total lipid phosphorus. Storage of the intact membranes, at either room temperature or at -20 degrees C, but not at -70 degrees C, resulted in a gradual and progressive hydrolysis of phosphatidylethanolamine to lysophosphatidylethanolamine. Over 60% of the total ethanolamine phospholipid was converted to the lyso form during a 2 week storage period. Incubation of the intact membranes at 37 degrees C produced a similar effect in one hour. Only small amounts of other glycerophospholipids were degraded under these conditions. Hydrolysis was specific for the sn-2 position as more than 80% of the fatty acids in the lysophosphatidylethanolamine were found to be saturated. Substitution of MgCl2 for CaCl2 in the precipitation step did not block the hydrolysis. It was concluded that rat brush-border membranes contain a Ca2+-independent phospholipase A2 with a high substrate preference for phosphatidylethanolamine. The physiological significance of this enzyme is not known. PMID- 3109483 TI - Resonance Raman study of reconstituted carotenoproteins incorporating astaxanthin and 15,15'-didehydroastaxanthin. AB - Two reconstituted carotenoproteins have been studied by resonance Raman spectroscopy. They were prepared from the apoprotein of the Asterias rubens carotenoprotein, asteriarubin and either astaxanthin or 15,15' didehydroastaxanthin. Spectral properties of dehydrocarotenoids are first discussed. The spectral properties of the complexes are compared to those of the free carotenoids and of other carotenoproteins containing astaxanthin, and possible protein-carotenoid interactions are discussed. Greater delocalisation of the pi-electron system in the central part of the polyene chain, and the role of lateral methyl groups in binding is emphasised. PMID- 3109485 TI - Regulative mechanisms in NADH- and NADPH-supported N-oxidation of 4-chloroaniline catalyzed by cytochrome b5-enriched rabbit liver microsomal fractions. AB - Incorporation into rabbit liver microsomal membranes of detergent-solubilized cytochrome b5 stimulates NADH-supported electron flow to ferric cytochrome P-450, but impairs NADPH-dependent reduction of the pigment such as to make the rates of both reactions equivalent; yet, in the enriched preparations NADPH-driven N oxidation of 4-chloroaniline proceeds at considerably higher rate than does the NADH-supported process. Analysis of transfer of the second electron to oxyferrous cytochrome P-450, as assessed by measuring substrate-induced reoxidation of ferrous cytochrome b5, reveals faster flow with NADH than with NADPH as the source of reducing equivalents. Quantification of the pools of cytochrome P-450 active in attack on the amine substrate in the presence of either reduced pyridine nucleotide, as well as measurements of maximum arylamine turnover suggest that the cofactor-dependent discrepancy in N-oxidase activity reflects differences in the rates of breakdown of the intermediary enzyme complexes. The NADH- and NADPH-supported pathway of N-oxidation in the cytochrome b5 supplemented microsomal fractions thus probably involves distinct forms of cytochrome P-450. Alternatively, functional linkage of the cofactor-specific electron-transfer chains to a single cytochrome P-450 species might yield aggregates of differing conformational state and catalytic capacity. The latter concept receives support from experiments with individually reconstituted enzyme systems. PMID- 3109484 TI - The pH dependence of the hydrolysis of chromogenic substrates of the type, Lys Pro-Xaa-Yaa-Phe-(NO2)Phe-Arg-Leu, by selected aspartic proteinases: evidence for specific interactions in subsites S3 and S2. AB - Variation in the kinetic parameters, kcat and Km, with pH has been used to obtain evidence for significant acid-dissociation processes in the hydrolysis of octapeptide substrates by three aspartic proteinases. These substrates are all cleaved at the peptide bond between a Phe (P1) and a p-nitroPhe (P1') residue resulting in a shift in absorbance at 300 nm that facilitates kinetic measurements. The substrates differ in the amino-acid residues present in the P3 and the P2 positions. Porcine pepsin, calf chymosin, and the aspartic proteinase from Endothia parasitica all show pH dependencies that imply that favorable or unfavorable interactions can occur with the S3 or S2 areas of the enzyme-active site. Examination of the crystallographically determined structure of the E. parasitica proteinase and consideration of the amino-acid sequence differences between the three enzymes suggests that the origin of the pH effects arises from favorable interactions between Glu-13 (COO-) of pig pepsin and Thr (OH) or His (ImH+) in P3 of a substrate. Similarly, Lys-220 (NH3+) of chymosin and a Glu (COO ) in P2 of a substrate may produce a favorable interaction and Asp-77 (COO-) of E. parasitica proteinase and a Glu (COO-) in P2 of a substrate may produce an unfavorable interaction. These results lead to possible explanations for subtle specificity differences within a family of homologous enzymes, and suggest loci for study by site-directed mutagenesis. PMID- 3109486 TI - Comparison of Streptomyces griseus and bovine trypsin by active site analysis using fluorescent acyl groups. AB - The preparation of fluorescence labeled acyl enzymes (Streptomyces griseus trypsin) was successfully carried out using specific trypsin substrates, 'inverse substrates'. The topographical analysis of the structures of the area around the active site was carried out by measuring the fluorescence spectra of the acyl enzyme preparations and these results were compared with those of bovine trypsin. It was found that the polarity of the active site vicinity at pH 5 was similar to that of bovine trypsin, whereas considerable differences were noticed at lower pH as a result of pH-induced transformation. Conformational changes of the active site induced by the interaction with the specific ligand were analyzed from the fluorescence spectra. In these responses the two enzymes were quite distinguishable. The two enzymes active sites were also different in the energy transfer experiments. The spatial arrangements of the catalytic residues relative to the intrinsic tryptophan residues were suggested to be substantially different for the two enzymes. PMID- 3109487 TI - Characterization of the aflatoxin B1-binding site of rat albumin. AB - A fluorescence-enhancement method was used to investigate the non-covalent interaction between aflatoxin B1 and rat albumin. Solvent-induced shifts in the emission spectrum of aflatoxin B1 provided evidence that the aflatoxin B1-binding site of rat albumin is a highly nonpolar environment. A dissociation constant of 20 microM was determined at 20 degrees C. The possibility that aflatoxin B1 binds one of the three major drug sites of albumin was investigated by ligand displacement experiments. Mechanisms whereby marker ligands displace aflatoxin B1 were further investigated by comparing the experimental binding parameters with those derived theoretically, assuming competitive binding. The results indicate that: aflatoxin B1 and phenylbutazone compete for a common high-affinity site on rat albumin; high-affinity binding of aflatoxin B1 and site-II marker ligands takes place independently; aflatoxin B1 does not compete with either cholate or warfarin for the same high-affinity site, but the simultaneous binding of warfarin or cholate negatively modulates the binding of aflatoxin B1 to albumin. Fluorescence energy-transfer studies show that the lone tryptophan residue, Trp 214, is not associated with the aflatoxin B1-binding site. PMID- 3109488 TI - Glutathione activation of a cysteine proteinase from Schistosoma mansoni. AB - A cysteine proteinase isolated from Schistosoma mansoni adults requires reduction by thiols for activation. The proteinase is located in the parasite digestive tract where it degrades hemoglobin released from host red blood cells. Reduced glutathione (GSH) has been shown to be effective in activation. Total glutathione concentration and the GSH/oxidized glutathione (GSSG) ratio were measured in whole blood lysate (3.2 mM, 284), serum (24 microM, 9.8) and material collected from the parasite digestive tract (4.2 mM, 137). The ratio of GSH/GSSG at which the enzyme displays half-maximal activity (Kox) is 1.0. Proteinase activation as a function of glutathione concentration and time was determined. The first-order reaction yielded a half-time of activation of 13 min at 5 mM. The second-order rate constant was 12.7 M-1 X min-1. The function of the proteinase and its possible regulation by glutathione activation are discussed. PMID- 3109489 TI - Purification and active site modification studies on glyoxalase I from monkey intestinal mucosa. AB - Glyoxalase I ((R)-S-lactoylglutathione methylglyoxal-lyase (isomerizing), EC 4.4.1.5) from monkey intestinal mucosa was purified to homogeneity. The purified enzyme had a molecular weight of 48,000, composed of two apparently identical subunits. Active-site modification was carried out on the purified enzyme in presence and absence of S-hexylglutathione, a reversible competitive inhibitor of glyoxalase I. Modification by tetranitromethane and N-acetylimidazole caused inactivation of the enzyme. Inactivation by N-acetylimidazole was reversible with hydroxylamine treatment, suggesting the importance of tyrosine residues for the activity of the enzyme. The enzyme was inactivated by 2-hydroxy-5-nitrobenzyl bromide, N-bromosuccinimide, 2,4,6-trinitrobenzenesulphonic acid, pyridoxal phosphate and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, indicating the importance of tryptophan, lysine and glutamic acid/aspartic acid residues for the activity of the enzyme. The enzyme was inactivated by diethyl pyrocarbonate and the activity was not restored by hydroxylamine treatment, suggesting that histidine residues may not be important for activity. Modification by N ethylmaleimide and p-hydroxymercuribenzoate did not affect its activity, indicating that sulphydryl groups may not be important for activity. These studies indicated that the amino acids present in the active site of glyoxalase I from intestinal mucosa which may be important for activity are tyrosine, tryptophan, lysine and glutamic acid/aspartic acid residues. PMID- 3109490 TI - A study on the in vitro interaction between tyrosinase and glutathione S transferase. AB - The actions of glutathione S-transferase and tyrosinase on the in vitro production of glutathionyl-3,4-dihydroxyphenylalanine and the dopachrome level in the presence of GSH and L-3,4-dihydroxyphenylalanine were studied. No clear evidence of complementarity between tyrosinase and glutathione S-transferase was observed; on the contrary, in the presence of glutathione S-transferase the glutathionyl-3,4-dihydroxyphenylalanine yield was lower than with tyrosinase only, as measured by HPLC. It is concluded that the spontaneous conjugation of GSH with dopaquinone should probably be high enough to scavenge the toxic quinone and to produce precursors for phaeomelanogenesis. PMID- 3109491 TI - Purification and properties of GM2 synthase, UDP-N-acetylgalactosamine: GM3 beta N-acetylgalactosaminyltransferase from rat liver. AB - A UDP-N-acetylgalactosamine:ganglioside GM3 beta-N acetylgalactosaminyltransferase which catalyzes the conversion of ganglioside GM3 to GM2 has been purified over 6300-fold from a Triton X-100 extract of rat liver particulate fractions by hydrophobic chromatography and affinity chromatography on GM3-acid-Sepharose. The purified enzyme has two identical subunits of 64,000 daltons. The enzyme has a pH optimum of pH 6.7-6.9 and requires divalent cations such as Mn2+ and Ni2+. In studies on substrate specificity GM3 containing N acetylneuraminic acid (GM3(NeuAc] and GM3 containing N-glycolylneuraminic acid were both good acceptors for the purified enzyme. The plots of the activity of transferase as a function of GM3(NeuAc) showed sigmoidal relationships. The oligosaccharide of GM3, sialyllactose, was also a good acceptor, which indicates that the preferred acceptor substrate has the possible structure NeuAc alpha 2- or NeuGc alpha 2-3 Gal beta 1-4Glc-OR. PMID- 3109492 TI - Evidence for the activation of phospholipases during acrosome reaction of human sperm elicited by calcium ionophore A23187. AB - Incubation of washed human sperm with [3H]- or [14C]arachidonic acid allowed a major incorporation of the label into phospholipids, provided that the final concentration of the fatty acid did not exceed 20 microM. A further challenge with calcium ionophore A23187 of spermatozoa suspended in a calcium-containing medium led to phospholipid hydrolysis, which could account for 10-12% of total cell radioactivity. Degradation products were identified as free, unconverted arachidonic acid, occurring with some diacylglycerol. Phospholipid hydrolysis was significant after 15 min of incubation and became maximal after 120 min. It was found to be calcium dependent, diacylglycerol and free arachidonate production occurring maximally at 2 mM and 5 mM CaCl2, respectively. Phosphatidylcholine and phosphatidylinositol were the most significantly degraded phospholipids after 60 min of incubation. Similar incubations conducted with 32P-labeled sperm confirmed the selective hydrolysis of phosphatidylcholine and revealed an increase production of phosphatidic acid probably due to a phosphorylation of diacylglycerol. Under the same conditions, one third of the cells remained motile and electron microscopy revealed that acrosome reaction was completed in 40% of the cells and displayed an intermediary state in 40-50% of the spermatozoa. Furthermore, a good parallelism was observed between the extent of the acrosome reaction and the extent of phospholipid hydrolysis promoted by increasing concentrations of A23187. It is concluded that calcium entry into the cells activates both a phospholipase A2 and a phospholipase C, leading to the production of substances, like lysophospholipid, diacylglycerol or phosphatidic acid, which may or may not be involved in acrosome reaction. PMID- 3109493 TI - Studies on the mechanism of hypertriglyceridemia in Tangier disease. Determination of plasma lipolytic activities, k1 values and apolipoprotein composition of the major lipoprotein density classes. AB - Mechanisms responsible for hypertriglyceridemia in Tangier disease were elucidated by an analysis of the plasma post-heparin lipolytic activities and the structural and metabolic properties of very low (VLDL) and low (LDL) density lipoproteins. The levels of lipoprotein lipase activity in six Tangier patients were significantly lower (P less than 0.001) than in 40 control subjects (8.1 +/- 3.3 (+/- S.D.) vs. 14.1 +/- 3.7 units/ml). In contrast, the levels of hepatic triacylglycerol lipase were higher (P less than 0.01) than in normal controls (14.4 +/- 3.9 vs. 9.3 +/- 4.0 units/ml). Because kinetic parameters such as Km or Vmax cannot be obtained with naturally occurring triacylglycerol-rich lipoproteins, the pseudo-first-order rate constant (k1) of triacylglycerol hydrolysis was used to assess the effectiveness of triacylglycerol-rich lipoproteins as substrates for lipoprotein lipase. The k1 values for Tangier VLDL (k1 = 0.017 +/- 0.002 min-1) were significantly lower (P less than 0.001) than the k1 values (0.036 +/- 0.008 min-1) for control VLDL. Both the Tangier and control LDL2 are similar in their resistance to the action of lipoprotein lipase, as shown by their low k1 values (0.002 +/- 0.001 and 0.001 +/- 0.001 min-1, respectively). The major compositional difference between the lipoproteins of Tangier disease and normal subjects was a significant increase in the percent content of apolipoprotein A-II in all lipoprotein particles with d less than 1.063 g/ml, with the greatest increase occurring in VLDL and the lowest in LDL2. These results were interpreted as indicating that, in Tangier disease, there is a lower reactivity of VLDL with lipoprotein lipase which may in part be attributed to the abnormal apolipoprotein composition. This finding, in conjunction with the reduced levels of lipoprotein lipase activity, may explain the hypertriglyceridemia in Tangier disease. PMID- 3109494 TI - Metabolism of 8,11,14,17-eicosatetraenoic acid by human platelet lipoxygenase and cyclooxygenase. AB - Human platelets metabolize 8,11,14,17-eicosatetraenoic acid primarily into 12 hydroxy-8,10,14,17-eicosatetraenoic acid. Several other hydroxy acids were also produced in small amounts via an indomethacin insensitive pathway. Platelet cyclooxygenase metabolized this acid only into 12-hydroxy-8,10,14 heptadecatrienoic acid. It was not possible to detect any cyclic products even though vesicular gland cyclooxygenase metabolizes this (n-3) acid to 17,18 dehydroprostaglandin E1 (Oliw, E.H., Sprecher, H. and Hamberg, M. (1986) J. Biol. Chem. 261, 2675-2683). PMID- 3109495 TI - Antiplatelet effect of butylidenephthalide. AB - Butylidenephthalide inhibited, in a dose-dependent manner, the aggregation and release reaction of washed rabbit platelets induced by collagen and arachidonic acid. Butylidenephthalide also inhibited slightly the platelet aggregation induced by PAF and ADP, but not that by thrombin or ionophore A23187. Thromboxane B2 formation caused by collagen, arachidonic acid, thrombin and ionophore A23187 was in each case markedly inhibited by butylidenephthalide. Butylidenephthalide inhibited the aggregation of ADP-refractory platelets, thrombin-degranulated platelets, chymotrypsin-treated platelets and platelets in the presence of creatine phosphate/creatine phosphokinase. Its inhibition of collagen-induced aggregation was more marked at lower Ca2+ concentrations in the medium. The aggregability of platelets inhibited by butylidenephthalide could be recovered after the washing of platelets. In human platelet-rich plasma, butylidenephthalide and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by epinephrine. Prostaglandin E2 formed by the incubation of guinea-pig lung homogenate with arachidonic acid could be inhibited by butylidenephthalide, indomethacin and aspirin. It is concluded that the antiplatelet effect of butylidenephthalide is mainly due to an inhibitory effect on cyclo-oxygenase and may be due partly to interference with calcium mobilization. PMID- 3109496 TI - Interleukin 1 preferentially stimulates the production of tissue-type plasminogen activator by human articular chondrocytes. AB - Interleukin 1, derived from human placenta, stimulates plasminogen activator activity in human articular chondrocytes. The stimulation of plasminogen activator activity can be abolished by preincubation of placental interleukin 1 with an antiserum to homogeneous 22K factor, a species of interleukin 1 beta, indicating that the stimulation of plasminogen activator activity is due to interleukin 1 and not contaminating factors. Chondrocytes produce three species of plasminogen activator, with apparent Mr approximately 50,000, 65,000 and 100,000 as determined after sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis with gels containing casein and plasminogen. Both placental interleukin 1 and 22K factor enhance the production of the species of Mr approximately 65,000 and 100,000. Comparison of the mobility of the plasminogen activator species on SDS-polyacrylamide gel electrophoresis with human urokinase (u-PA) and human melanoma tissue-type plasminogen activator (t-PA) and studies with antibodies to these enzymes indicate that the Mr approximately 50,000 species is a u-PA and the Mr approximately 65,000 a t-PA. The Mr approximately 100,000 species is possibly an enzyme-inhibitor complex. Interleukin 1 therefore appears to enhance the production of t-PA and a putative enzyme-inhibitor complex. Abolition of plasminogen activator activity in the fibrin plate assay with antibodies to t-PA and u-PA also confirms enhanced t-PA production on interleukin 1 stimulation, though there is also evidence for increased cell associated production of u-PA. PMID- 3109497 TI - The interaction between heparin and antithrombin III: a comparison of two different heparin-dye conjugates. AB - The interactions of antithrombin III with two heparin-dye conjugates have been compared using their fluorescence anisotropy. The first, heparin labelled with 5 isothiocyanatofluorescein, where the dye was mostly bound to unsulphated glucosamine residues, exhibited binding which was characteristic of heparin with a low affinity for antithrombin III. The second, heparin labelled with a reactive naphthalene dye (DENMT), showed similar binding character. However, when the heparin was treated with an amino group blocking agent prior to labelling with DENMT, the resultant heparin-dye conjugate showed binding behaviour, the strength of which was consistent with heparin molecules having both high and low affinity for antithrombin III. Heparin molecules with a high affinity for antithrombin III did not possess free amino groups. The implications of these findings are discussed with regard to the reliability of the data obtained using heparin fluorescein conjugates. PMID- 3109498 TI - Calmodulin and calmodulin-binding proteins in the renal brush border. AB - The calmodulin content of renal brush-border membrane vesicles, prepared by Mg2+ precipitation in EGTA-containing solutions, amounts to 1.8 micrograms per mg protein. The amount and the distribution of this EGTA-insensitive calmodulin was determined in membrane and cytoskeletal fractions prepared from the brush-border membrane vesicles by extraction with Triton X-100. The Triton X-100 insoluble pellet contains 21.2% of the protein and 52.2% of the EGTA-insensitive calmodulin, which amounts in this fraction to 4.4 micrograms per mg protein. Treatment of the Triton X-100 insoluble pellet, consisting of the microvillar core residue, with ATP and Mg2+ results in the solubilization of a relatively small number of proteins among which are actin, myosin, calmodulin and several calmodulin-binding proteins. The solubilization is partially reversible and a fraction of the proteins can be precipitated by centrifugation after the enzymatic hydrolysis of ATP. Readdition of ATP to the pellet results in the resolubilization of myosin, part of the actin, an 115-kDa calmodulin-binding protein and calmodulin. The calmodulin content of the final extract was 61.8 micrograms per mg protein. We have found roughly the same distribution pattern of calmodulin and ATP-solubilized, calmodulin-binding proteins in renal and intestinal brush-border preparations. The calmodulin content, however, as well as the relative amount of the calmodulin-binding proteins versus actin are about 4 to 5-times higher in intestinal than in renal microvillar core residues. PMID- 3109499 TI - Guanine nucleotide regulation of the pertussis and cholera toxin substrates of rat glioma C6 BU1 cells. AB - Rat glioma C6 BU1 cells contain a pertussis toxin substrate of 40 kDa which does not appear to be identical with Gi,Go or transducin. The GTP analogue, GTP[gamma S], inhibited the rate of pertussis toxin-catalysed ADPribosylation of this protein, while the GDP analogue GDP[beta S] stimulated this reaction. A protein of the same kDa value was ADPribosylated by cholera toxin in the absence of added guanine nucleotides. It is suggested that this 40 kDa protein can be a substrate for both cholera and pertussis toxins under appropriate conditions. PMID- 3109501 TI - [Kinetic properties of NADP-specific isocitrate dehydrogenase from bovine adrenals]. AB - At low concentrations of Mg2+ or Mn2+ the reaction catalyzed by isocitrate dehydrogenase from bovine adrenal cortex proceeds with a lag period which disappears as a result of the enzyme saturation with Mn2+ or Mg2+. The nu o versus D,L-isocitrate concentration curve is non-hyperbolic, which may be interpreted either by the presence of two active sites with different affinity for the substrate (K'mapp = 2.3 and 63 microM) within the enzyme molecule or by the "negative" cooperativity of these sites. The apparent Km value for NADP lies within the range of 3.6-9 microM. High concentrations of NADP inhibit isocitrate dehydrogenase (Ki = 1.3 mM). NADP.H inhibits the enzyme in a mixed manner with respect to NADP (Ki = 0.32 mM). In the presence of NADP.H the curve nu o dependence on NADP concentration shows a "negative" cooperativity between NADP binding sites. The reverse enzyme-catalyzed reaction of reductive carboxylation of 2-oxoglutarate does not exhibit any significant deviations from the Michaelis Menten kinetics. The Km value for 2-oxoglutarate is 120 microM, while that for NADP.H is 10 microM. PMID- 3109500 TI - [The level and activity of molecular forms of monooxygenase P-450b and P-450c during their separate and consecutive induction in the liver]. AB - Studies with monospecific antibodies to individual forms of monooxygenases P-450b (phenobarbital-induced) and P-450c (3-methylcholanthrene-induced) by immunochemical, kinetic and spectral methods revealed differences in the dynamics of xenobiotic-induced changes in the content and monooxygenase activity of the total microsomal CO-binding hemoprotein and of its molecular forms. Correction was made in the estimation of the benzphetamine-demethylase and benzpyrene hydroxylase activities based on the content of specific forms of P-450b and P 450c. Since consecutive injection of phenobarbital and 3-methylcholanthrene (or vice versa) is accompanied by selective induction of the corresponding isoforms and the redistribution of the relative content of P-450b and P-450c in the total pool of cytochrome P-450 in rat liver microsomes, a conclusion was drawn that these molecular forms are induced by different populations of hepatocytes. This conclusion was confirmed by data from immunohistochemical analysis. PMID- 3109502 TI - [Interaction of sheep haptoglobin with trypsin inhibitors]. AB - It was found that polymeric sheep haptoglobin C interacts with duck egg ovomucoid and with maize trypsin inhibitor. These inhibitors do not block the region in haptoglobin C molecule which is responsible for the formation of its complex with hemoglobin. The binding of the natural protein inhibitors is suggestive of homology of the haptoglobin site involved in the interaction with the substrate specific site of trypsin. It is assumed that the regions in these protein molecules adjacent to the active and specific sites also possess a high degree of homology. PMID- 3109503 TI - Effects of parenteral and enteral nutrition on postnatal development of the small intestine and pancreas in the rabbit. AB - Although TPN is used frequently in young infants, little information is available regarding its effect on postnatal development of the gut. The effect of total parenteral nutrition (TPN) and intragastric (IG) alimentation on ontogeny of the small intestine was examined in infant rabbits starting at 10-12 days. Animals were killed at 17-19 days. Body weight, organ weight and weight of segments of proximal, mid and distal small intestine were measured. Intestinal mucosa was scraped, weighed and homogenized for estimation of protein, DNA and disaccharidases. Na+ transport was examined in short-circuited jejunum. Weight gain was similar in controls, sham-treated and TPN animals, but was significantly reduced in IG animals. TPN induced precocious development of sucrase and maltase activity and glucose-stimulated Na+ transport, despite causing a significant decrease in mucosal weight and DNA and pancreatic amylase. IG alimentation also induced precocious development of sucrase, maltase and glucose-stimulated Na+ transport. Thus TPN, despite producing mucosal atrophy and decreased pancreatic exocrine development, stimulates accelerated postnatal maturation of the small intestine. PMID- 3109504 TI - Inhibition of follicle-stimulating hormone-induced ovulation by indomethacin in the perfused rat ovary. AB - In isolated, perfused ovaries of rats treated with pregnant mare's serum gonadotropin (PMSG), purified preparations of ovine follicle-stimulating hormone (FSH) (oFSH-211B) and rat FSH (rFSH-I-6), 100 ng/ml, were found to induce ovulations (4.8 +/- 0.9, n = 4, and 6.4 +/- 2.0, n = 5, ovulations per ovary, respectively). Indomethacin (5 micrograms/ml) added to the perfusate inhibited this ovulatory effect and exogenous prostaglandin F2 alpha (PGF2 alpha) (1 microgram/ml), or prostaglandin E2 (PGE2) (0.5 microgram/ml), reversed the blockade. Ovine FSH and rFSH had only a weak stimulatory effect on estradiol release, and only rFSH caused a significant increase in progesterone accumulation. Indomethacin reduced the stimulatory effect of rFSH on progesterone release, and this effect was reversed by PGE2 but not by PGF2 alpha. In a 6-h incubation experiment with preovulatory rat follicles, we tested the biological activity of gonadotropins used to induce oocyte maturation. The concentration of FSH used in the perfusion experiments induced oocyte maturation in more than 88% of the oocytes studied. The data confirm earlier findings that FSH can induce ovulations and show that prostaglandins are involved in this process. The data also indicate that prostaglandins might be involved in the FSH-induced increase of progesterone levels. PMID- 3109505 TI - Metabolism of progesterone by preimplantation mouse blastocysts in culture. AB - This study examined the question whether or not preimplantation mouse blastocysts can metabolize progesterone (P). When young (Day 4) and implanting (Day 5) blastocysts were cultured in supplemented Eagle's minimum essential medium containing 0.4 microM [3H]P, metabolism of P and formation of metabolites were noticed at 10 h of culture. The metabolites accumulated in medium as the culture continued to 118 h. Three of the four metabolite fractions were identified, by crystallization to constant sp. act., to be 5 alpha-pregnane-3,20-dione and 3 beta-hydroxy-5 alpha-pregnan-20-one (or allopregnanolone), accounting for 22 and 57% of radioactivity, respectively, and a small amount (1-10%) of 3 alpha-hydroxy 5 alpha-pregnan-20-one. This suggests that both delta 4-5 alpha-reductase and 3 alpha- and 3 beta-hydroxysteroid dehydrogenase are active. Day 5 blastocysts were much more active than Day 4 blastocysts in P metabolism. It is suggested that the ability of blastocysts to metabolize P could produce the following effects in the adjacent endometrium: a lessening of P effects; and consequently a change in P estrogen interaction; and possible effects from the metabolites. These local effects of embryos on the endometrium may be important for embryonic development and implantation. PMID- 3109506 TI - Cationic modulation of follicle-stimulating hormone binding to granulosa cell receptor. AB - Magnesium (Mg2+) increases binding of follicle-stimulating hormone (FSH) to membrane-bound receptors and increases adenylyl cyclase activity. We examined the effects of divalent and monovalent cations on FSH binding to receptors in granulosa cells from immature porcine follicles. Divalent and monovalent cations increased binding of [125I]iodo-porcine FSH (125I-pFSH). The divalent cations Mg2+, calcium (Ca2+) and manganese, (Mn2+) increased specific binding a maximum of 4- to 5-fold at added concentrations of 10 mM. Mg2+ caused a half-maximal enhancement of binding at 0.6 mM, whereas Ca2+ and Mn2+ had half-maximal effects at 0.7 mM and 0.8 mM, respectively. The monovalent cation potassium (K+) increased binding a maximum of 1.5-fold at an added concentration of 50 mM, whereas the monovalent cation (Na+) did not increase binding at any concentration tested. The difference between K+ and Na+ suggested that either enhancement of binding was not a simple ionic effect or Na+ has a negative effect that suppresses its positive effect. Ethylenediamine tetraacetic acid, a chelator of Mg2+, prevented binding of 125I-pFSH only in the presence of Mg2+, whereas pregnant mare's serum gonadotropin, a competitor with FSH for the receptor, prevented binding in both the absence and the presence of Mg2+. Guanyl-5 ylimidodiphosphate (Gpp[NH]p) inhibited binding of 125I-pFSH in the absence or presence of Mg2+, but only at Gpp(NH)p concentrations greater than 1 mM. We used Mg2+ to determine if divalent cations enhanced FSH binding by increasing receptor affinity or by increasing the apparent number of binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109507 TI - Divergent effects of cations on follicle-stimulating hormone- and forskolin activated adenylyl cyclase in granulosa cells. AB - The divalent cations magnesium, calcium and manganese, and the monovalent cation, potassium, but not sodium, enhance binding of [125I]iodo-porcine follicle stimulating hormone to follicle-stimulating hormone (FSH) receptors in membranes of porcine granulosa cells via an increase in the apparent number of binding sites. The objective of the present studies was to determine if increased binding of FSH to its receptor causes increased adenylyl cyclase activity in response to FSH, or conversely, if enhancement of the cyclase or one of its components causes increased binding, or if the two processes are modulated independently. MgCl2 and CaCl2, which both enhance binding in intact cells and in cell-free membrane preparations, had opposite effects on cyclase-MgCl2 stimulatory, CaCl2 inhibitory. In isotonic NaCl, MgCl2 did not enhance binding, but it did increase FSH-stimulated production of cyclic adenosine 3',5'-monophosphate (cAMP). NaCl did not enhance FSH binding and it did not enhance cyclase in cell-free membranes, but it did increase FSH- and forskolin-stimulated cAMP production in intact cells. In intact cells, maximally effective concentrations of MgCl2 and KCl were additive in enhancing cAMP production whereas the effects of NaCl and KCl together were synergistic. The results indicate that although cationic effects on FSH binding are not causally related to effects on cyclase, the cationic microenvironment of the granulosa cell membrane is critical to both FSH receptor and adenylyl cyclase functions. PMID- 3109508 TI - The effects of melatonin and hypothyroidism on estradiol and gonadotropin levels in female Syrian hamsters. AB - Since melatonin injections administered near the end of the daily photoperiod influence both gonadal and thyroid hormones in the female hamster, the present study was designed to compare the effects of melatonin and hypothyroidism on the reproductive system and to determine whether thyroid status influenced the action of melatonin on the regulation of the hormones of reproduction. The effects of daily melatonin injections were determined in control hamsters, in hamsters rendered hypothyroid with thiourea, and in hypothyroid hamsters receiving thyroxin (T4) hormone replacement. As previously reported, melatonin injections disrupted estrous cyclicity, disrupted the normal pattern of gonadotropin secretion, and resulted in atrophy of the uterus and vagina. These changes coincided with depressed serum and pituitary prolactin (PRL), and depressed levels of estradiol. The effects of melatonin on uterus, vagina, ovary, and on gonadotropin levels were not prevented by T4 replacement, with the exception of a melatonin-induced increase in serum follicle-stimulating hormone (FSH). This suggested that the cessation of estrous cyclicity was not primarily a result of thyroid deficiency. Hypothyroidism, however, like melatonin, resulted in a reduced number of developing and mature follicles and corpora lutea in the ovaries, and in reduced uterine weight. It also produced follicular atresia, reduced the circulating levels of estradiol, and resulted in reduced incidence of estrus smears. T4 replacement, for 2 weeks, prevented the decline in mature follicles and corpora lutea, reduced the extent of follicular atresia, increased circulating levels of estradiol, and increased uterine weight. PRL and luteinizing hormone (LH) data also provided evidence for antagonistic effects of melatonin and T4 in female hamsters. These data raise the question whether melatonin-induced changes in circulating levels of T4 play a role in the seasonal cycles of reproductive competence in the female hamster. PMID- 3109509 TI - Microtubules and the calcium-dependent regulation of rat granulosa cell steroidogenesis. AB - The possible relationship between calcium and microtubules in the regulation of granulosa cell steroidogenesis was assessed by using agents known to alter microtubule-tubulin equilibrium together with the ionophore A23187, an antibiotic that facilitates the movement of calcium across plasma membranes. Using immunofluorescence and morphometric analysis, we determined alterations in microtubule organization and overall cell shape, respectively, in response to ionophore-stimulated production of progesterone and 20 alpha-hydroxypregn-4-en-3 one (20 alpha-OH-progesterone) during 24 h of culture. In addition, the influences of colchicine and nocodazole, two agents known to induce microtubule depolymerization, and of taxol, an agent that stabilizes tubulin polymers, on calcium-dependent regulation of granulosa cell progestin production in vitro were examined. Cells cultured as controls were flattened, highly irregular in outline, and associated with a complexly organized, well-spread cytoplasmic network of microtubules. In contrast, those maintained in the presence of increasing concentrations of ionophore were progressively more circular and smooth in outline, occupied less area on the growth surface, and contained cytoplasmic arrays of microtubules considerably less extensive than those of the controls and occupying areas defined by the more regular cellular perimeters. While progestin production in the absence or presence of a submaximally stimulatory concentration of A23187 was increased by both colchicine and nocodazole, the microtubule depolymerizing agents had little to no effect on the production of the steroids by granulosa cells maximally stimulated by the ionophore. However, both basal and ionophore-induced progestin production were unaltered by taxol except at a concentration of 10 microM in the presence of 0.25 micrograms/ml A23187.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109510 TI - Plasminogen activator activity in cumulus-oocyte complexes of gonadotropin treated rats during the periovulatory period. AB - Two types of plasminogen activator (tissue-type, tPA; urokinase-type, uPA) have been demonstrated in ovarian granulosa cells, but only tPA activity was found in denuded oocytes. Immature rats were treated subcutaneously with 20 IU pregnant mare's serum gonadotropin (PMSG) to stimulate follicle maturation, followed 2 days later by an injection of 10 IU human chorionic gonadotropin (hCG) to induce ovulation. Cellular plasminogen activator activities were determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis followed by a fibrin overlay technique. Cumulus-oocyte complexes from rats before and after PMSG treatment contained low amounts of tPA, but not uPA, activity. After hCG treatment, tPA activity showed a time-dependent increase, reaching a maximum at 24 h after injection. At 12 and 24 h after hCG treatment, uPA activity was also detected. The appearance of high molecular weight lysis zones further suggested the formation of plasminogen activator-inhibitor complexes. Morphological analysis indicated that the increases in oocyte tPA activity were correlated with the extent of cumulus cell expansion and dispersion. In denuded oocytes, tPA activity also progressively increased during the periovulatory period to a maximum at 24 h after hCG treatment. In contrast, neither uPA activity nor activator-inhibitor complex was detected. Secretion of the proteases was measured in the conditioned media of cumulus-oocyte complexes cultured for 24 h in vitro. Substantial increases in tPA release were found in complexes obtained at 8 and 12 h after hCG injection, with lower secretion from complexes obtained at 24 h after hCG treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109511 TI - Partial purification and characterization of human sperminogen. AB - A recently recognized non-proacrosin zymogen referred to as sperminogen has been purified from human spermatozoa, and several of its properties have been determined. The purification procedure included acid extraction of washed ejaculated sperm at pH 3.0, followed by gel filtration of the solubilized extract over a Sephadex G-75 superfine column. The sperminogen eluted from the column in a single band that was completely separated from the proacrosin band. This separation was confirmed by a gelatin-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (gelatin-SDS-PAGE) zymograph. This zymograph also demonstrated that the final sperminogen preparation contained four forms of zymogen, with molecular weights between 32,000 and 36,000. At neutral pH, the sperminogen was converted into spermin, its enzymatically active form, yielding a sigmoidal curve typical of zymogen autoactivation. The effects of several factors on the rate of this autoconversion indicate specific differences between sperminogen and proacrosin. Spermin hydrolyzed N-alpha-benzoyl-L-arginine ethyl ester (BzArgOEt), and was inhibited by lima bean trypsin inhibitor, pancreatic trypsin inhibitor, N acetyl-L-leucyl-L-leucyl-L-argininal (leupeptin), and tosyl-L-lysine chloromethyl ketone, indicating that the enzyme has a trypsin-like specificity and probably belongs to the class of trypsin-like enzymes. Since acrosin is generally believed to be the only trypsin-like enzyme in mammalian sperm, the demonstration of human sperminogen and spermin necessitates further inquiry into the functions and the relationships between sperm proteinase systems. PMID- 3109512 TI - Steroid production in vitro by granulosa, theca, and luteal cells from goat ovaries. AB - Basal progesterone (P4) production by isolated goat ovarian cells in vitro was in the order corpus luteum (CL) greater than granulosa (G) greater than theca (TH), while estradiol (E2) production was in the order TH greater than G greater than CL. In G cells, various concentrations (0.01 to 100 micrograms/ml) of luteinizing hormone (LH), human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) increased P4 and E2 secretion. Testosterone (T, 10(-9) to 10(-5) M) produced dose-dependent increases in P4 and E2 secretion. Testosterone and LH together had an additive effect on E2 secretion. The combined effect of the lower (less than 10(-6) M) concentrations of T and LH on P4 production was marginally higher than either agent alone, but the increase was statistically insignificant; at higher concentrations of T (10(-6) and 10(-5) M) in combination with LH, P4 secretion was similar to that with LH alone, but was significantly (p less than 0.01 and less than 0.001, respectively) less compared to that with T alone. Follicle-stimulating hormone and T together produced a synergistic effect on E2 and an additive effect on P4 production. In TH cells, a dose-dependent increase in P4 and E2 production was observed with LH and hCG, but the effect of FSH was not significant. Testosterone produced a dose-dependent increase in P4 and E2 secretion. Testosterone and LH together induced higher steroid production than either agent alone. However, the increase was not statistically significant compared to T alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109513 TI - Comparative effects of diverse vertebrate gonadotropins on androgen formation in vitro from testes of roosters and mice. AB - A study was carried out to compare the androgen formation activity of gonadotropins from diverse vertebrate species by rooster and mouse testes in vitro. The dispersed testicular interstitial cells from 6- to 7-wk-old mice or testicular slices from 3- to 4-mo-old roosters were incubated with varying doses of luteinizing hormones (LHs)/gonadotropins (GTHs) in Medium 199 containing isobutyl-methyl-xanthine and N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid buffer (pH 7.4) at 34 degrees C (mice) or 37 degrees C (roosters) for 4 hr under continuous aeration of 95% O2-5% CO2 in a Dubnoff incubator shaken at 100 cycles/min. Androgen in the medium was measured by radioimmunoassay. The results revealed that dose-related androgen formations were obtained both in rooster and mouse systems in response to stimulations of all LHs/GTHs tested. The mouse system was more responsive to mammalian LHs and placental GTHs, less responsive to LHs from chickens, frogs, and turtles, and extremely unresponsive to piscine GTHs. In contrast, the rooster system was highly responsive to LHs from both mammals and chickens in androgen formation; it was also responsive to LHs from turtles and frogs as well as to piscine GTHs, although with relatively lower sensitivity. The rooster testis system is thus suitable for in vitro bioassay of LHs/GTHs from virtually all vertebrate classes, whereas the mouse testis system is more suitable for bioassay of mammalian LHs and placental GTHs. The differential androgen formation potencies of the diverse vertebrate GTHs in testis systems between roosters and mice indicate that a divergence exists in the testicular receptors between the two animal species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109514 TI - Beta-microseminoprotein (beta-MSP) is not an inhibin. AB - Beta-microseminoprotein (beta-MSP), a sperm-coating antigen isolated from human seminal plasma, has apparent structural identity with "beta-inhibin" isolated from the same source. Publication of the amino acid sequence of beta-MSP revealed a greater than 96% homology with "beta-inhibin," with only a proline-threonine substitution at positions 39 and 40, and the omission of a glycine at position 93. Due to the nearly identical sequences of "beta-inhibin" and beta-MSP, we examined the ability of beta-MSP and its tryptic peptides to inhibit basal follicle-stimulating hormone (FSH) secretion from rat pituitary cells in culture, the inhibin bioassay. Whole pituitaries collected from 250- to 300-g male rats were dispersed enzymatically and plated onto 24-well culture dishes for 3 days. beta-MSP and its tryptic peptides were dissolved in cell culture medium, applied to the pituitary monolayer cell cultures, and incubated for an additional 3 days. FSH levels in the medium were determined by radioimmunoassay. A partially purified preparation of inhibin and our in-house inhibin standard, both prepared from porcine follicular fluid (pFFl), were included in the same assay. Whereas the partially purified inhibin from pFFl showed a dose-dependent inhibition of FSH secretion, with a 50% inhibitory dose (ID50) of 50 ng, which paralleled that of the standard, beta-MSP and its tryptic peptides failed to depress FSH levels in the medium at any of the doses tested (10-10,000 ng/ml). We conclude that beta MSP is not an inhibin under our assay conditions. PMID- 3109515 TI - Feedback regulation of gonadotropic hormone secretion in neonatal pigs. AB - The effect of castration and of administration of charcoal-treated porcine follicular fluid (pFF) containing inhibin-like activity on plasma concentration of gonadotropic hormones was studied in neonatal pigs. Plasma follicle stimulating hormone (FSH) concentration averaged 25.1 +/- 1.5 ng/ml (mean +/- SEM) in 1-wk-old females and gradually declined to 20.2 +/- 0.7 ng/ml 6 wk later. Ovariectomy did not significantly influence plasma FSH concentration. In males, concentration averaged 8.0 +/- 0.7 ng/ml before castration but rose significantly within 2 days after castration. Injection of luteinizing hormone-releasing hormone (LHRH) did not influence plasma FSH concentrations in intact males, but did in females and in 7-wk-old males castrated at 1 wk. Plasma luteinizing hormone (LH) concentrations in 1-wk-old females (2.2 +/- 0.4 ng/ml) gradually declined and were not influenced by castration. Concentrations of plasma LH in 1 wk-old male piglets (2.8 +/- 0.7 ng/ml) were not significantly influenced by castration within 2 days but were significantly higher 6 wk later. LHRH induced a significant rise in plasma LH concentrations in all animals. Injection of pFF resulted in a decline of plasma FSH concentrations in intact and castrated males and in intact females, but did not influence plasma LH concentrations. These data demonstrate a sex-specific difference in the control of plasma FSH, but not in plasma LH concentration in the neonatal pig. Plasma FSH concentrations, but not plasma LH concentrations, are suppressed by testicular hormones in 1-wk-old piglets. Plasma FSH concentrations can be suppressed in both neonatal male and female pigs by injections of pFF. PMID- 3109516 TI - Relationships between histological signs of atresia, steroids in follicular fluid, and gonadotropin binding in individual bovine antral follicles during postpartum anovulation. AB - Two experiments were conducted to determine the relationship between histological signs of atresia, gonadotropin binding, and steroids in fluid of medium-sized bovine follicles during postpartum anestrus. In Experiment I, ovaries of 21 cows were removed on Days 7, 14, 28, 42, or 56 after parturition. In Experiment II, ovaries of 29 cows were removed between Days 20 and 30 postpartum after 48 or 96 h of either saline (0.9% NaCl, 5 ml) or luteinizing hormone-releasing hormone (LHRH; 500 ng/5 ml saline) injections given every 2 h via jugular cannulas. Two to 10 follicles, 4.0-7.9 mm in diameter, were removed per pair of ovaries. Follicles were classified as normal, intermediate, atretic, or luteinized atretic, depending on their micromorphology. In both Experiments I and II, follicles classified as normal had 50-80% lower (p less than 0.05) concentrations of progesterone and 2- to 7-fold greater (p less than 0.05) concentrations of estradiol than atretic follicles. However, concentrations of androstenedione and gonadotropin-binding sites were similar in normal and atretic follicles. Atretic follicles had degenerative granulosa with several pyknotic nuclei, thick theca, and little distinction between theca and granulosa. Intermediate follicles showed slight signs of degeneration and had 2- to 3-fold greater (p less than 0.05) concentrations of progesterone than normal follicles. Concentrations of estradiol did not differ (p greater than 0.10) between normal and intermediate follicles. Equal proportions of normal and atretic medium-sized follicles were located on the ovaries bearing the corpus albicans from pregnancy (CAP).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109517 TI - Changes in ovarian norepinephrine synthesis throughout the follicular and luteal phases. AB - The aims of this study were to determine norepinephrine (NE) synthesis in follicle-dominated and luteal-dominated ovaries as compared to oviducts, and to correlate NE synthesis with NE content and turnover rates. Rats were injected with pregnant mare's serum gonadotropin (PMSG) on Day 28. Ovaries and oviducts were removed during the follicular (Days 28-30) and luteal (Days 31-40) phases and incubated for 2 h with [3H] tyrosine. Tritiated and endogenous NE were determined by high-performance liquid chromatography. Ovarian NE synthesis from [3H] tyrosine was reduced by more than 50% within 24 h after PMSG injection, with a second 50% reduction on Day 30, concomitant with the endogenous gonadotropin surge. The lowest NE synthesis (15% of control values) was observed in the luteinized ovary on Day 33. Ovarian NE synthesis from [3H] L dihydroxyphenylalanine (DOPA) was similar in control and PMSG-injected rats on selected days during the follicular and luteal phases. Oviductal NE synthesis decreased after PMSG injection, but was similar to control values during the luteal phase. Ovarian NE content was modestly reduced between Days 30 and 35, whereas oviductal NE content was not altered. After an injection of alpha-methyl p-tyrosine on Day 33, ovarian and oviductal NE content decreased exponentially over a period of 10 h. The NE turnover rates were similar in control and PMSG injected rats in both tissues. The following conclusions were reached: Circulating gonadotropins appear to suppress ovarian NE synthesis during the follicular phase. The low NE synthesis by the luteinized ovary is consistent with previous reports that follicles, but not corpora lutea (CL), contain catecholamine elements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109518 TI - Electric inhomogeneity in membranes of Characean internode influenced by light/dark transition, O2, N2, CO2-free air and extracellular pH. AB - The electric membrane potential as functions of position and time of Characean internode has been studied using a modified water-film electrode technique. Between the low-conductance hyperpolarized region (called the H-region or acidic region) and the high-conductance depolarized region (D-region), there is a difference in the direction of responses to light-off and -on stimulations. In darkness the membrane potential becomes hyperpolarized in the D-region, whereas it is depolarized in the H-region at the steady state. The potential difference between D- and H-regions, delta Vm, is increased by exposure to pure O2, N2, or CO2-free air. When the amount of water surrounding the internode is limited, the formation of an electric pattern occurs rapidly. In contrast, the recovery is delayed. The membrane potential of the D-region is sometimes hyperpolarized significantly with lowering of the extracellular pH to 7.5, while the potential of the H-region is slightly depolarized. This seems to be an all-or-none type response. However, the electric profile is always homogenized with the pH of 6.8. Thus, the pH around 7.5 may be a threshold level to open/close putative OH- (or H+) channels of the D-region. PMID- 3109519 TI - [Thermostable leukocyte alpha-glycoprotein: immunochemical study and enzyme activity research]. AB - Using immunochemical analysis with standard antisera, leukocyte thermostable alpha-glycoprotein (LT alpha G) was shown to be distinct from lactoferrin, lysozyme, and fibronectin. The determination of peroxidase and nonspecific elastase in immune precipitates of LT alpha G gave negative results. Affinity sorption of LT alpha G onto the pus protein component was revealed. Purified LT alpha G had amidolytic activity in response to a substrate for elastase (p nitroanilide succinyl-trialanyl). The ability of LT alpha G to cause the hydrolysis of substrates for thrombin, kallikrein, plasmin was investigated. The identity of LT alpha G and granulocyte elastase is suggested. PMID- 3109520 TI - [Thrombocyte aggregation in plasma and whole blood during hyperventilation (hypocapnia) in cats]. AB - Platelet aggregation in platelet rich plasma (PRP) and whole blood was simultaneously studied in acute experiments on cats in hypocapnic conditions. ADP induced aggregation increase was determined in PRP and whole blood. Contradictory results were obtained during platelet aggregation induced by collagen and arachidonic acid: increased aggregation in PRP and decreased aggregation in whole blood. The data obtained suggest that ADP is a risk factor for the onset of intravascular thrombosis. PMID- 3109521 TI - [Disorders of repair processes in the lymphocytes of schizophrenia patients, cultured in vitro]. AB - Repair disorders of DNA damage induced by gamma-radiation and 4-nitroquinoline-1 oxide treatment in cultivated lymphocytes of patients with schizophrenia. 13 criteria were used for estimation of repair activity (reactivation of viral host cells) repair synthesis, reparation of DNA breaks, formation of spontaneous and induced sister chromatid exchanges. PMID- 3109522 TI - [Infrared method of studying the action of vasoactive substances on cerebral circulation]. AB - A method for the investigation of cerebral blood flow changes under the influence of vasoactive drugs has been suggested. The method is based on continuous infrared radiation and registration of the reflection from the local brain region through the cerebral cranium. The experiments were conducted on anesthetized cats. The dependence of Pa CO2 on the recorded parameters is shown. The changes in the cerebral blood flow (in conventional units) determined by the alterations of the infrared radiation reflection are shown upon the injection of 1.2 microgram/kg, 2.5 micrograms/kg and 5 micrograms/kg of noradrenaline. PMID- 3109523 TI - Fibrinogen-independent aggregation and deaggregation of human platelets: studies in two afibrinogenemic patients. AB - Platelets from two afibrinogenemic patients were used to determine whether fibrinogen is essential for platelet aggregation and to examine whether released fibrinogen contributes to the stabilization of platelet aggregates when platelets have been induced to aggregate and release their granule contents by stimulation with thrombin. The addition of adenosine diphosphate (ADP) to platelet-rich plasma (PRP) or to suspensions of washed platelets from the afibrinogenemic patients caused the formation of small aggregates, which was either not inhibited or only slightly inhibited by the F(ab')2 fragments of an antibody to fibrinogen but was inhibited by an antibody (10E5) to glycoprotein IIb/IIIa. Thus there is a component of ADP-induced platelet aggregation that is not dependent on fibrinogen or other plasma proteins but is dependent on glycoprotein IIb/IIIa. There was little difference in the extent of aggregation and the release of granule contents of normal and afibrinogenemic platelets in response to the release inducing agents collagen, platelet-activating factor (PAF), sodium arachidonate, or thrombin. With normal or afibrinogenemic platelets, aggregation by thrombin (0.2 U/mL or higher) was not inhibited by the F(ab')2 fragments of an antibody to human fibrinogen. Deaggregation by combinations of inhibitors of platelets aggregated by 1 U/mL thrombin showed no difference between platelets from afibrinogenemic and control subjects, indicating that released fibrinogen does not make a major contribution to the stabilization of platelet aggregates formed by thrombin stimulation. PMID- 3109524 TI - Immunologic aberrations, HIV seropositivity and seroconversion rates in patients with hemophilia B. AB - Because there have been reports that factor IX concentrate is less immunosuppressive and therefore factor IX users have less immunologic aberrations, we have studied a group of 22 patients with hemophilia B and six patients with factor VIII deficiency and high titer inhibitors with respect to lymphocyte numbers and function, human immunodeficiency virus (HIV) serology, and factor usage. This group was compared to 111 patients with hemophilia A and a group of 28 healthy male volunteer controls. When the study began in 1983, the majority of patients with hemophilia B and with higher titer factor VIII inhibitors were seronegative, 77% and 83% respectively, as compared to only 30% of patients with hemophilia A. At that time the factor IX users also had milder immune aberrations than the hemophilia A group. However, with time and increasing clotting factor concentrate usage, seroconversion and more striking abnormalities in immune function have occurred in the hemophilia B group. In a subgroup of 16 patients with hemophilia B studied twice, the incidence of seropositivity increased from 31% in 1983 to 69% in 1985. We thus conclude that factor IX concentrate in itself is not less immunosuppressive than factor VIII concentrate. Seroconversion in factor IX concentrate users appears to be lagging behind seroconversion in factor VIII concentrate users, perhaps secondary to the lower cumulative dosage of concentrate that patients with hemophilia B utilize. PMID- 3109525 TI - Gamma interferon and aplastic anemia. PMID- 3109527 TI - A possible role of thromboxane A2 in endothelium in maintaining resting tone and producing contractile response to acetylcholine and arachidonic acid in canine cerebral arteries. AB - Endothelial thromboxane A2 (TXA2) in maintaining the resting tone and producing the contractile response to acetylcholine (ACh) and arachidonic acid was studied in canine cerebral artery. The spontaneous release of TXB2 from cerebral artery was about tenfold higher than that of coronary, mesenteric and saphenous arteries. The resting tone, the release of TXB2 and the contraction produced by arachidonic acid were decreased by the presence of cyclooxygenase inhibitor, TXA2 synthetase inhibitor, TXA2 antagonist and rubbing of the luminal side of preparations. The contraction produced by ACh was inhibited by the presence of the above inhibitors and rubbing of the preparations without decreasing the release of TXB2. These results suggest that the resting tone of canine cerebral artery and the contractile response to arachidonic acid are related to activation of TXA2 synthesis in the endothelium. PMID- 3109526 TI - Immunological specificity and mechanism of action of IgG lupus anticoagulants. AB - Although observations have implied that lupus anticoagulants have immunologic specificity toward anionic phospholipids, this assumption has been directly demonstrated in only one patient with a monoclonal IgM paraprotein. We tested the generality of this hypothesis directly by isolating five IgG lupus anticoagulants from patients with lupuslike syndromes and/or thrombosis. IgG lupus anticoagulant fractions were isolated free of other plasma proteins and free of contaminating phospholipid by adsorption to and elution from cardiolipin-cholesterol-dicetyl phosphate liposomes, followed by chromatography on protein A-Sepharose. Cardiolipin liposomes, but not phosphatidylcholine liposomes, were capable of removing all, or nearly all, lupus anticoagulant activity from patient plasma. The affinity-purified IgG preparations reacted with cardiolipin, phosphatidylserine, phosphatidylinositol, and phosphatidic acid, but not with phosphatidylcholine or phosphatidylethanolamine, and inhibited calcium-dependent binding of prothrombin and of factor X to phosphatidylserine-coated and to cardiolipin-coated surfaces. F(ab')2 fragments retained lupus anticoagulant activity and bound to cardiolipin in an enzyme-linked immunosorbent assay (ELISA). Anticardiolipin and lupus anticoagulant activity were both present in acidic fractions on isoelectric focusing. These data strongly suggest that most, if not all, lupus anticoagulants are antibodies that have immunologic specificity towards anionic phospholipids, thereby blocking the calcium-mediated binding of vitamin K-dependent coagulation factors to coagulation-active phospholipid surfaces. PMID- 3109528 TI - Endothelium-dependent contractions in arteries and veins. AB - Endothelium-dependent contractions of isolated veins can be induced with arachidonic acid and thrombin. Anoxia causes endothelium-dependent contractions in a variety of isolated arteries and veins. Rapid stretch and acetylcholine contract cerebral arteries with, but not those without endothelium. Acetylcholine (and serotonin) cause endothelium-dependent contractions in the aorta of the spontaneously hypertensive, but not that of the normotensive rat. PMID- 3109529 TI - Polyamines and the synthesis of estradiol-regulated growth factors in rat mammary cancer in culture. AB - We have recently provided evidence to suggest that the polyamine pathway plays an essential role in the expression of the growth-promoting effect of estradiol (E2) regulated growth factors in the N-nitrosomethylurea (NMU) induced rat mammary tumor cultured in vitro in the soft agar clonogenic assay. To further explore the interaction between the polyamine pathway and autocrine control of tumor growth by E2, we tested whether, in our system, polyamines play a role in the synthesis of E2-regulated growth factors. Conditioned medium (CM) obtained from tumors treated with E2 and the polyamine biosynthesis inhibitor alpha-difluoromethyl ornithine (DFMO) (1 mM) no longer exhibited the colony-stimulating effect which was consistently observed with E2-CM. Such growth promoting activity was restored in a dose-dependent fashion with CM obtained from tumors treated with E2, DFMO, and increasing concentrations of spermidine (from 1 to 100 microM). Conditioned medium obtained from tumors treated with DFMO with and without spermidine in the absence of E2 had no discernible effects on colony formation. The colony stimulating effect of the CM employed could not be accounted for by the contaminating presence in the media of E2, DFMO, or polyamines. These results indicate that, in our system, the polyamine pathway plays an important role in the synthesis of E2-regulated growth factors. PMID- 3109531 TI - Role of the mechanical impairment on the ventilatory response to CO2 in chronic airway obstruction. AB - The purpose of this study was to assess the relationship between the breathing pattern response to CO2 and the severity of mechanical impairment in twenty patients with COLD. The CO2 response was compared to that of a control group of twelve normal subjects. All patients had airway obstruction (FEV1 = 40 +/- 14% of predicted; means +/- SD) and hyperinflation (FRC = 154 +/- 23% of predicted). Tidal volume (VT), inspiratory and total cycle duration (TI, TT), occlusion pressure (P0.1) and endtidal PCO2 were measured at rest and during hyperoxic CO2 rebreathing. On the same day, in all patients, arterial blood gas analysis, spirometric and plethysmographic measurements were made. The slope (S) of the P0.1 response (SP 0.1) to increasing endtidal PCO2 was negatively correlated with airway resistance (r = -0.59; p less than 0.01). Although the flow response, S(VT/TI), was positively and closely correlated with SP 0.1 (r = 0.88; p less than 0.001), it also appeared to be independently influenced by obstruction (p less than 0.01). The tidal volume response, SVT, was principally correlated with inspiratory capacity (r = 0.90; p less than 0.001) and also, independently, with Vmax50 (p less than 0.01). SVT was diminished in seventeen patients, ten of whom only had a decreased S(VT/TI). The shortening in TI during hypercapnia was most marked in patients with the greatest S(P0.1), who did not have arterial hypercapnia at rest. These results suggest: that the poor VT response to CO2 in COLD patients is principally caused by a limitation in inspiratory volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109530 TI - Methylthioadenosine phosphorylase in human breast cancer. AB - Methylthioadenosine (MTA) phosphorylase activity was measured in 47 biopsies from primary breast cancers (n = 34) and metastatic tumors (n = 13). Most specimens were also evaluated by DNA flow cytometry and determination of estrogen and progesterone receptor contents. Median MTA phosphorylase activity was 317 pmol/mg protein/min (range 50-1312 pmol/mg protein/min), but great variations were observed. Samples from four individuals had very low MTA phosphorylase activity (less than or equal to 70 pmol/mg protein/min). No correlation with aneuploidy, receptor status, or the presence of metastases in the lymph nodes could be demonstrated. However, MTA phosphorylase activity showed a significant (p = 0.009) negative correlation with the fraction of cells in the S-phase of the cell cycle. PMID- 3109532 TI - An ambulatory system for long-term continuous monitoring of transcutaneous PCO2. AB - Apparatus suitable for continuous, ambulatory transcutaneous PCO2 monitoring is described. This consists of a Stow-Severinghaus transcutaneous sensor with a miniaturized amplifier and recorder. Its performance characteristics and vulnerability to artefact have been assessed. The procedure for prolonged ambulatory recording is outlined. The response time (for 67% of change) was 13 s in dry gas and 5 min on skin (the reasons for this difference are discussed). With 28 subjects, the between subject correlation (r) of transcutaneous and arterial PCO2 measurements was 0.97. After equilibration, recorded values drifted only occasionally. When it did occur, the average was 0.03 kPa X h-1 in dry gas and 0.1 kPa X h-1 on skin. There was no evidence of artefact due to changes in temperature or blood flow. Movement artefact were eliminated using an adequate attachment procedure. A number of healthy volunteers were monitored for up to 12 h while freely ambulant. In all subjects, small fluctuations in transcutaneous PCO2 were observed, of less than 0.5 kPa. The apparatus is of value in the assessment of conditions and situations in which acute change in ventilation has been implicated and for investigation of normal respiratory physiology with freely ambulant subjects. PMID- 3109533 TI - Changes in myocardial norepinephrine levels in response to stress, exercise and aging in control and T. cruzi-infected rats. AB - The effect of mild acute exercise (swimming for 1 h), restraint for 1 h and fasting for 48 h on myocardial norepinephrine concentration was compared with rats "at rest" using 320 control and chronically T. cruzi-infected rats at 50, 110, 200 and 380 days of age. Ventricular norepinephrine concentrations of control and similarly aged T. cruzi-infected rats were different for 2 of 4 "at rest" groups. Significant and opposite differences in ventricular norepinephrine were observed for restrained T. cruzi-infected rats when compared to controls ( 35% in 50-day old rats and +40% in 110-day old rats). Exercised, "at rest" and fasted control rats presented a significant age-dependent decrease of ventricular norepinephrine concentration, which was not observed for restrained control rats. Norepinephrine levels of pooled atria from 120-day old "at rest" T. cruzi infected rats were significantly lower than those from non-infected controls, whereas no difference was found in serotonin levels. The lability of myocardial norepinephrine levels in T. cruzi-infected rats suggests, but does not demonstrate, that there is a disturbance of the cardiac sympathetic control. PMID- 3109534 TI - Interferon-gamma: involvement in human disease. AB - The susceptibility to infection in various situations is discussed, emphasizing the role of interferon-gamma as a vital mediator of host resistance. PMID- 3109535 TI - Cytoprotective effects of disodium cromoglycate on rat stomach mucosa. AB - The cytoprotective effects of the anti-asthmatic drug, disodium cromoglycate (DSCG), on gastric mucosal necrosis induced by ethanol in rats were studied. Subcutaneous, but not oral, DSCG prevented the formation of gastric lesions and this effect was dose-dependent between 1.25 and 40 mg kg-1, with an ED50 value of 6.8 mg kg-1. Maximal cytoprotection occurred 15-30 min after DSCG treatment. Histological examination revealed that DSCG effectively protected the gastric mucosa against ethanol-induced vascular congestion, haemorrhage, epithelial desquamation and mucosal oedema. Enhanced production of endogenous prostaglandins, which are known cytoprotective compounds, could not explain the mucosal protection. At a dose of 40 mg kg-1, DSCG did not change prostaglandin E2 or 6-keto-prostaglandin F1 alpha concentrations in gastric mucosal tissue, although its cytoprotective activity was partially inhibited by prior treatment of the animals with indomethacin. PMID- 3109536 TI - The role of dilatation in bilharzial ureters. AB - Endoscopic dilatation of bilharzial ureteric strictures was carried out in 35 men and four women. The procedure had to be repeated in 10 patients after 2 months and three patients have required regular dilatation every 4 months for the last 2 years. The selection of patients is important since they should have neither an active lesion nor a stenotic calcific one. PMID- 3109537 TI - Treatment of hidradenitis suppurativa with the carbon dioxide laser. PMID- 3109538 TI - The flow cytometer. PMID- 3109539 TI - The economics of mental health services. PMID- 3109540 TI - Reversal of female sterilisation. PMID- 3109541 TI - Cannabis: dangers and possible uses. PMID- 3109542 TI - Evidence of beta cell dysfunction which does not lead on to diabetes: a study of identical twins of insulin dependent diabetics. AB - Ten non-diabetic identical twins of insulin dependent diabetics were studied to see whether they showed changes in insulin secretion. The twins were selected because more than 11 years had elapsed since the diagnosis of the diabetic twin and they were therefore unlikely to develop diabetes, and they had had islet cell antibodies. Despite similar glucose concentrations to the controls the twins had greater total immunoreactive insulin responses to both oral (mean 3280 (SD 699) versus 2338 (1110) pmol/dl at 180 minutes; p less than 0.05) and intravenous (1346 (690) versus 699 (294) pmol/dl at 30 minutes; p less than 0.05) glucose challenge. The C peptide responses to intravenous glucose were also increased consistent with increased insulin secretion. In addition, basal serum proinsulin concentrations in the twins were increased (2.1 (1.2) versus 1.0 (0.3) pmol/dl; p less than 0.01) and remained so throughout both tests. These twins, who were unlikely to develop insulin dependent diabetes, showed evidence of beta cell dysfunction which does not progress to diabetes. PMID- 3109543 TI - Ulcerogenicity of piroxicam: an analysis of spontaneously reported data. AB - Previous reports have suggested that piroxicam may be more ulcerogenic than other non-steroidal anti-inflammatory drugs (NSAIDs) in use. Critics have attributed this putative relation to flawed comparisons of spontaneously reported data. In this study cases of upper gastrointestinal bleeding, perforation, and ulcer reported to the Food and Drug Administration's spontaneous reporting system over 12 years were examined. Reporting rates for eight NSAIDs were compared over identical periods of their marketing life cycles. After adjustments were made for the heterogeneity in the underlying reporting rates the difference in rates between piroxicam and the other drugs was considerably reduced but piroxicam retained its top ranking among the drugs; however, large and clinically important differences in the frequency of cases of upper gastrointestinal bleeding, perforation, and ulcer between piroxicam and the rest of the NSAIDs compared probably do not exist. PMID- 3109545 TI - Relation between phenotype and banal melanocytic naevi. AB - In a study of risk factors for the development of melanocytic naevi in relation to the pathogenesis of malignant melanoma 197 white adults were examined by four dermatologists and naevus counts correlated with several other features. Highly significant associations were found between large numbers of banal acquired melanocytic naevi and the ability to tan easily without burning (skin types 3 and 4; relative risk 4.6), brown or hazel eyes (relative risk 3.5), green or grey eyes (relative risk 3.5) and brown or black hair (relative risk 3.7). No significant associations with numbers of naevi were shown for parity or use of oral contraceptives or other steroid hormones. This is the first study to find any relation between melanocytic naevi and phenotypic factors in a white population. PMID- 3109546 TI - Chronic renal failure associated with topical application of paraphenylenediamine. PMID- 3109544 TI - Low serum selenium concentration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy. AB - Serum selenium concentrations were found to be significantly lower in women with intrahepatic cholestasis of pregnancy than in women with normal pregnancies during the last trimester of pregnancy and post partum. The activity of the selenoenzyme glutathione peroxidase had a significant positive correlation with selenium concentration and it was also significantly lower in women with the disease. These findings suggest that selenium deficiency and reduced glutathione peroxidase activity are associated with the aetiopathogenesis of intrahepatic cholestasis of pregnancy. PMID- 3109547 TI - Severe bradycardia due to interaction of timolol eye drops and verapamil. PMID- 3109548 TI - Feasibility of a large prospective study in general practice: an Italian experience. Gruppo di Studio sulla Pressione Arteriosa nell'Anziano. AB - A study of blood pressure control in elderly outpatients was carried out with the participation of 444 Italian general practitioners. Of 4096 patients aged 65 years or over who were considered for recruitment, 3959 (96.7%) fulfilled all the criteria of admission and were followed up for 12 months. The findings regarding one of the aims of the study--that is, to assess the feasibility of a large scale trial in general practice--are reported. Most (87%) of the doctors completed the study. Their adherence to the protocol was highly satisfactory, leading to an acceptable quality of work. Patients' compliance was also good; 98.6% (3898) of the patients who had fulfilled the admission criteria agreed to participate in the study, and only 4% (158) dropped out. Both of these observations support the feasibility of carrying out prospective studies in general practice. The creation of networks of general practitioners who are prepared to carry out research in their practices would allow treatment and preventive measures to be studied simply and at low cost in the appropriate setting. PMID- 3109549 TI - How can good general practitioner care be achieved? AB - It has been shown that to provide a high standard of care general practitioners probably need to book consultations at intervals of at least 10 minutes. In this study the maximum list size for which a general practitioner might be expected to provide a high standard of care was determined from calculations of the time spent consulting, based on various consultation rates and list sizes and assuming that consultations were 10 minutes long. If good quality care is to be provided and is to include the range of services suggested in the government's recent green paper average list sizes should probably be no more than 1750, and lower in areas of high demand and high need. In addition to this, minimum standards could be determined for such measures as facilities available in surgeries, practice records, and accessibility of doctors to ensure that basic services were offered by all general practitioners. PMID- 3109550 TI - Diagnostic classification of the aetiology of mental retardation in children. PMID- 3109551 TI - Vaccine related poliomyelitis in non-immunised relatives and household contacts. PMID- 3109552 TI - Prognosis for infants born at 23 to 28 weeks' gestation. PMID- 3109553 TI - Acyclovir update. PMID- 3109554 TI - Doctors' double standards on alcohol. PMID- 3109555 TI - Doctors as nutrition educators? PMID- 3109556 TI - Optimising antiemesis in cancer chemotherapy. PMID- 3109558 TI - Recurring meningitis: beware the normal looking ear. PMID- 3109557 TI - Randomised trial of treatment of hypertension in elderly patients in primary care. PMID- 3109559 TI - Effect of breast conservation on psychological morbidity associated with diagnosis and treatment of early breast cancer. PMID- 3109560 TI - Prescribing in pregnancy. PMID- 3109561 TI - Vegetarian diet in mild hypertension. PMID- 3109562 TI - The debasing of medicine in the Soviet Union. PMID- 3109563 TI - Death in the clouds. PMID- 3109564 TI - Dose dependent response of symptoms, pituitary, and bone to transdermal oestrogen in postmenopausal women. PMID- 3109565 TI - A new health region for London? PMID- 3109566 TI - Scott: 75 years on. PMID- 3109567 TI - Hyposensitisation. PMID- 3109568 TI - Doctors and the death penalty: an international issue. PMID- 3109569 TI - Evaluating mass training in cardiopulmonary resuscitation. PMID- 3109570 TI - Causes of blindness in schoolchildren. PMID- 3109571 TI - Laboratory control of oral anticoagulants. PMID- 3109572 TI - Atopic manifestations in the acquired immune deficiency syndrome: response to recombinant interferon gamma. AB - Six patients with the acquired immune deficiency syndrome (AIDS) had exacerbations or recurrences of previously quiescent atopic disease when they developed immunodeficiency. Four developed a different atopic illness from that suffered previously. Atopic symptoms developed within three months after the patients developed AIDS or during prodromal illness. Two of the patients were treated with recombinant interferon gamma: both showed a striking improvement in symptoms and cellular immunity. These results indicate that cellular immunity, through interferon gamma, may have a role in regulating atopic disease. PMID- 3109573 TI - Exaggerated postural vasoconstrictor reflex in Raynaud's phenomenon. AB - The central and local regulation of capillary blood flow in the finger was studied by the local xenon-133 washout technique in women with primary Raynaud's phenomenon, men with vibration induced white finger, and their respective sex matched controls. The vasoconstrictor response to venous stasis of 40 mm Hg elicited by local reflex was normal in both types of Raynaud's phenomenon. Change in posture from lying to sitting induced vasoconstriction in all groups, which was abolished by proximal nervous blockade. The vasoconstrictor response to sitting was augmented in both groups of subjects with Raynaud's phenomenon compared with their sex matched controls. These results show the existence of central and local postural vasoconstrictor reflexes in normal fingers. In both types of Raynaud's phenomenon there was hyperreactivity of the central sympathetic nervous system to orthostatic stress and normal function of digital arterioles and postganglionic sympathetic nerve fibres. PMID- 3109574 TI - Subcutaneous calcium heparin versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicentre prospective randomised trial. AB - One hundred patients with phlebographically proved acute deep vein thrombosis of the legs were prospectively randomised into two treatment groups to compare the safety and efficacy of subcutaneous calcium heparin versus intravenous sodium heparin administered by constant infusion pump. The dose of heparin was determined by daily measurement of the kaolin cephalin clotting time. Treatment was maintained for up to 14 days, after which phlebography was repeated. Of 49 patients who received subcutaneous calcium heparin, two showed an increase in thrombus size, while eight showed complete lysis. In the 47 patients who received intravenous sodium heparin thrombus increased in size in 13 while only one showed evidence of complete lysis. These differences were significant. There were no significant differences between the two groups in the incidence of serious complications, although almost half of those receiving intravenous heparin had some minor problem with the constant infusion pump and just over half of those receiving subcutaneous heparin had some bruising at the injection site. This study showed that subcutaneous calcium heparin was more effective in helping lyse existing thrombus and preventing its propagation than intravenous sodium heparin. PMID- 3109576 TI - Effect of negative ion generators in a sick building. PMID- 3109575 TI - Randomised comparison of early versus late induction of labour in post-term pregnancy. AB - In a prospective randomised study of mothers referred for prolonged pregnancy (around the 42nd week) 214 (group 1) were submitted to attempted induction of labour and 195 (group 2) assigned to continue for a further week without intervention. Strict selection criteria were used for the certainty of term. Mothers in group 2 were given regular non-stress tests to ensure fetal wellbeing, as were those in group 1 in whom induction failed. In group 1, 48 (23%) out of 210 first attempted inductions failed. In group 2, 135 (69%) of the births started spontaneously as compared with 38 (18%) in group 1. The mean duration of labour was 7.5 hours in each group. There was no significant difference in incidence of operative delivery, use of analgesics, or signs of perinatal asphyxia. Significantly more children in group 1 needed phototherapy for hyperbilirubinaemia. There was a clustering of births in the late afternoon and evening, which was most pronounced in group 1. A policy of vigilant non intervention up to the 44th completed week of pregnancy does not appear to jeopardize mother or fetus. PMID- 3109577 TI - Subunit influenza vaccination in adults with asthma: effect on clinical state, airway reactivity, and antibody response. PMID- 3109578 TI - Acute mesenteric ischaemia caused by Schistosoma mansoni infection. PMID- 3109579 TI - Inability of trained nurses to perform basic life support. PMID- 3109580 TI - Fibreoptic bronchoscopy and the use of antibiotic prophylaxis. PMID- 3109581 TI - General practice consultations: is there any point in being positive? AB - A group of 200 patients who presented in general practice with symptoms but no abnormal physical signs and in whom no definite diagnosis was made were randomly selected for one of four consultations: a consultation conducted in a "positive manner," with and without treatment, and a consultation conducted in a "non positive manner," called a negative consultation, with and without treatment. Two weeks after consultation there was a significant difference in patient satisfaction between the positive and negative groups but not between the treated and untreated groups. Similarly, 64% of those receiving a positive consultation got better, compared with 39% of those who received a negative consultation (p = 0.001) and 53% of those treated got better compared with 50% of those not treated (p = 0.5). PMID- 3109582 TI - How effective is case finding at detecting diabetes and hypertension in the community? PMID- 3109583 TI - Acute admissions of patients with sickle cell disease who live in Britain. AB - All acute admissions of patients with sickle cell disease who lived in the London borough of Brent and attended this hospital were analysed for a period of one year. Sixty three of the 211 patients who were followed up by the haematology department required 161 acute admissions during the year. Most admissions (126) were for the 42 patients with homozygous sickle cell disease; 147 (91%) were for vaso-occlusive episodes, 142 of which were for painful crises, three for cerebrovascular accidents, and two for renal papillary necrosis. Preschool children with sickle cell disease were admitted predominantly with limb pain, whereas in schoolchildren and adults the incidence of trunk pain was higher. Twenty four of the 93 episodes of trunk pain culminated in an episode of severe visceral sequestration usually affecting the lungs, the liver, or the mesenteric circulation. Two patients died: an 18 month old baby with an acute splenic sequestration crisis and a 19 year old man with a severe girdle syndrome (sickling in the mesenteric circulation, liver, and lungs). Infective episodes were rare (11 episodes) but severe: one haemophilus meningitis, two salmonella infections, and three aplastic crises due to parvovirus infections. The average duration of the hospital stay was 7.4 days per admission. It is concluded that because sickle cell disease causes appreciable morbidity in older children, adolescents, and adults a systematic approach to management is needed to deal with acute episodes such as sequestration syndromes. PMID- 3109584 TI - Halothane hepatitis in children. AB - It is often stated that halothane hepatitis in children is nonexistent or extremely rare. This syndrome occurred in seven children aged between 11 months and 15 years, one of whom, a 3 1/2 year old boy, died with fulminant hepatic failure. All the children had received multiple halothane anaesthetics (range 2 6, median 3). In all cases other causes of liver diseases were excluded, and in all but one the diagnosis was confirmed serologically by antibodies to halothane altered liver cell membrane antigens. These findings suggest that halothane hepatitis occurs in children, and the risk of halothane hepatitis should therefore be considered when choosing which agents to use in children who require multiple anaesthetics. PMID- 3109585 TI - Portraits from memory. 13--Professor Robert Douglas Lockhart, MD, FRSE (1894 1987). PMID- 3109586 TI - ABC of AIDS. Management of early HIV infection. PMID- 3109587 TI - Lyme disease. PMID- 3109588 TI - Drug formularies in hospitals. PMID- 3109589 TI - Original pack dispensing. PMID- 3109590 TI - Childhood leukemia and nuclear establishments. PMID- 3109591 TI - Irritable bowel syndrome as a cause of chronic pain in women attending a gynaecological clinic. PMID- 3109592 TI - Pinch skin grafting or porcine dermis in venous ulcers. PMID- 3109593 TI - Clinical algorithms: Infertility. PMID- 3109594 TI - Clinical algorithms: irregular vaginal bleeding. PMID- 3109595 TI - Indigenous strongyloidiasis in Nottingham. PMID- 3109596 TI - Long term urethral catheterization in the elderly. PMID- 3109597 TI - What contribution has cardiac surgery made to the decline in mortality from coronary heart disease. PMID- 3109598 TI - Ethics committees and research in children. PMID- 3109599 TI - Children, bikes, and money. PMID- 3109600 TI - Standards for blood pressure measuring devices. PMID- 3109601 TI - Oncogenes and cancer. PMID- 3109602 TI - Influence of salt on glycaemic response to carbohydrate loading. AB - The effect of dietary salt on glycaemic responses to different test meals was investigated. Eight healthy male volunteers ate four test meals on consecutive mornings and in random order; the meals were 50 g carbohydrate taken as a 20% glucose solution or as boiled macaroni with and without supplementation with 6 g salt. In contrast with other reports, no significant differences in peak plasma glucose concentrations or areas under the plasma glucose curves could be established. These findings do not support a beneficial effect of salt restriction on glycaemic control in diabetes. PMID- 3109603 TI - Delayed cerebellar ataxia: a new complication of falciparum malaria? AB - Twelve cases of an unusual phenomenon of ataxia were investigated in otherwise well, conscious patients recovering from a febrile attack of presumed falciparum malaria. The ataxia occurred as the fever was subsiding, usually after an afebrile period of two to four days. The delay between onset of fever and the ataxia was three to four weeks. Peripheral blood of all the patients contained gametocytes of Plasmodium falciparum, and in some cases ring stages. The ataxia was most noticeable in the legs and the clinical picture suggested selective impairment of the cerebellar system. Signs of improvement appeared in a few weeks but complete recovery took one to four months. The most likely pathogenic mechanism of the ataxia in these cases was an immune reaction triggered by the malaria parasite and affecting the cerebellum or its connections, or both. PMID- 3109605 TI - Death and serious injury in child motorcyclists. PMID- 3109606 TI - Spinal injuries and BMX bicycles. PMID- 3109607 TI - Long term effect of oestrogen replacement therapy on bone mass as measured by dual photon absorptiometry. PMID- 3109604 TI - Controlled investigation of deaths from asthma in hospitals in the North East Thames region. AB - One hundred and thirty deaths definitely or potentially due to asthma occurring in hospitals in the North East Thames region over one year were identified from death certificates and Hospital Activity Analysis records. Thirty five of these deaths were considered after independent assessment to have been directly due to asthma. Control patients who left hospital alive after acute asthma attacks were selected and matched with cases for sex, age, and hospital. Management was compared in the two groups. Inadequate monitoring, including failure to monitor arterial blood gas values, and inadequate use of nebulised beta agonists occurred significantly more often in fatal cases. Use of sedation, inadequate treatment with steroids, exposure to potentially toxic doses of aminophylline, and inadequate clinical assessment were more common in cases than controls, but not significantly so. Failure to institute artificial ventilation contributed to seven deaths. Assessors considered important defects in management to have occurred in 83% (29/35) of the cases and 40% (14/35) of the controls. Nevertheless, most of the hospital deaths (19/35) were considered not to have been preventable. Eight other deaths in the region were attributed to the complications of asthma or its treatment. Three of these were associated with gastrointestinal bleeding and one with perforation of a duodenal ulcer. Before considering policies aimed at speeding admission to hospital of patients with acute attacks of asthma it is crucial that the general standard of hospital care offered to all patients with asthma should be improved. PMID- 3109608 TI - Complications of nose piercing. PMID- 3109610 TI - Appointment and mobility of general practitioners. PMID- 3109609 TI - Evaluation of portable haemoglobinometer in general practice. AB - The HemoCue system for estimating haemoglobin was evaluated within urban general practice. It gave excellent results when used within a laboratory environment (on 103 paired samples) but disappointing ones when evaluated by practice nurses within general practice (on 235 paired samples). The most likely source of error was inadequate mixing of the blood specimens before sampling, which might be obviated by using a rotating mixer. It is emphasised that equipment intended for use in general practice should be evaluated under normal working conditions envisaged. PMID- 3109612 TI - Immunisation before school entry: should there be a law? PMID- 3109611 TI - Bicycle accidents in childhood. AB - The results of a 10 year study of bicycle fatalities and an eight year study of serious non-fatalities are reported for urban Brisbane (population 1,000,000). There were 845 serious non-fatal bicycle accidents and 46 fatalities during the study. Boys were involved in 86% of accidents. Boys have an accident rate of 134.21 per 100,000 population at risk and a fatality rate of 5.06 per 100,000 at risk. Serious bicycle accidents have increased by 50% in this decade; but considering fatal cases alone, no secular trend was evident over the 10 year period of the study. This suggests that an increase in the overall rate of bicycle accidents has been in part compensated by less serious injuries. In 70% of fatalities children had head injuries, and 87% of fatalities followed a collision between a cyclist and a motor vehicle or a train. Bicycle accidents on the roads most commonly occur to boys aged between 12 and 14 years on a straight road at "mid-block" between 3 and 5 pm in clear weather conditions and in daylight. It is concluded that injuries and fatalities after bicycle accidents can be reduced by protecting children's heads, separating child cyclists from other road traffic, or educating and training both cyclists and other road users in safe behaviour. The compulsory use of helmets and the restriction of access to the roads by child cyclists to reduce injuries are, however, still controversial in many areas. PMID- 3109613 TI - Radcliffe Infirmary, Oxford, 1937-8. PMID- 3109614 TI - ABC of AIDS. Tumours. PMID- 3109615 TI - Rubella susceptibility and the continuing risk of infection in pregnancy. PMID- 3109616 TI - Ruptured abdominal aortic aneurysm presenting with ureteric colic. PMID- 3109617 TI - LMSSA: a back door entry into medicine. PMID- 3109618 TI - Lower oesophageal contractility as an indicator of brain death in paralysed and mechanically ventilated patients with head injury. PMID- 3109619 TI - Alcohol and ischaemic heart disease in middle aged British men. PMID- 3109620 TI - Treatment of palindromic rheumatism with chloroquine. PMID- 3109621 TI - Ulcerogenicity of piroxicam: an analysis of spontaneously reported data. PMID- 3109623 TI - Are isolated maternity units run by general practitioners dangerous? PMID- 3109622 TI - Impact of cuts in acute beds on services for patients. PMID- 3109624 TI - Drums begin to beat in the waiting list jungle. PMID- 3109625 TI - Cervical smears: new terminology and new demands. PMID- 3109626 TI - Should sympathomimetics be available over the counter? PMID- 3109628 TI - Hospices for children? PMID- 3109627 TI - Special units for acute upper gastrointestinal bleeding. PMID- 3109629 TI - Regional secure units: arriving but under threat. PMID- 3109630 TI - Why do women live longer and is it worth it? PMID- 3109631 TI - Services for people with epilepsy. PMID- 3109632 TI - Colposcopy in a family planning clinic: a future model? AB - The first year's experience of a satellite colposcopy clinic in the Glasgow Family Planning Centre was analysed. Establishment of the clinic was supervised by an experienced member of the colposcopy team at the department of gynaecology, Western Infirmary, Glasgow, who trained one of the family planning centre's staff. Close links were thus maintained with the hospital clinic to which patients were referred for treatment. The policy at the new colposcopy clinic was to study prospectively all women in the hospital catchment area whose cervical smears were reported as abnormal. In 58 of 162 such patients there was at least moderate dyskaryosis and the cytologist's recommendation had been referral for colposcopy. In 104 cases the changes were either atypia alone or mild dyskaryosis and a repeat smear was recommended within three to 12 months; 18 of these patients had grade II or III cervical intraepithelial neoplasia on biopsy, and relying on repeat smears would have resulted in an 11.7% false negative rate. If an atypical cytological picture is to be an indication for colposcopy clinics attached to family planning centres may have an important role, given satisfactory training and close links with central specialist colposcopy clinics. PMID- 3109633 TI - Cigar and pipe smoking and myocardial infarction in young men. AB - The effect of cigar and pipe smoking on the risk of myocardial infarction was evaluated in an interview study of 572 men with non-fatal first myocardial infarctions and 934 hospital controls. The study was conducted in the north eastern United States from 1980 to 1983. All subjects were 40-54 years of age, and none had smoked cigarettes for at least two years. Among men who had never smoked cigarettes the relative risk of myocardial infarction for those who smoked at least five cigars a day, compared with not smoking cigars and pipes and allowing for other risk factors, was estimated to be 1.7 (95% confidence interval 0.6 to 4.8). Among ex-smokers of cigarettes the corresponding estimate for those who smoked at least five cigars a day was 4.5 (2.2 to 9.2). The estimates for men who smoked fewer cigars, or pipes, were closer to 1.0 and not significant. Men who stop smoking cigarettes and switch to at least five cigars a day apparently continue to have an increased risk of myocardial infarction, possibly because they continue to inhale the smoke. PMID- 3109634 TI - Early respiratory experience and subsequent cough and peak expiratory flow rate in 36 year old men and women. AB - Earlier work on the respiratory health of members of the Medical Research Council's national survey of health and development (1946 birth cohort) was extended to age 36. At that age measures of peak expiratory flow rate and respiratory symptoms, elicited by the MRC chronic bronchitis questionnaire, were made in 3261 cohort members. In both men and women lower peak expiratory flow and higher respiratory morbidity were independently associated not only with current indices of poor social circumstances and cigarette smoking but also with poor home environment at age 2 years and lower respiratory tract illness before age 10. The findings provide additional evidence for a causal relation between childhood respiratory experience and adult respiratory disease. PMID- 3109635 TI - Migration of gall stones. AB - The factors influencing the migration of gall stones are ill understood. Altogether 331 patients undergoing cholecystectomy were studied prospectively. The diameters of the cystic and common bile ducts and of stones in the gall bladder and bile ducts were measured. Increasing pressure was applied to the freshly excised gall bladder in an attempt to evacuate stones through the cystic duct. Stones passed in 33 (60.0%) of patients with choledocholithiasis, 45 (67.2%) of patients with pancreatitis, and 7 (3.2%) of patients without either pancreatitis or choledocholithiasis. Stones migrated in 6 (3.0%) who had a normal cystic duct diameter (less than or equal to 4 mm) and in 46 (32.5%) with a duct over 4 mm diameter. Common bile duct stones were often larger than the diameter of the cystic duct and when reintroduced into the gall bladder would not migrate. The passage of debris (less than or equal to 1 mm) through the cystic duct bore no relation to the presence or absence of choledocholithiasis or a dilated cystic duct. Small stones (1-4 mm diameter) must migrate to initiate and facilitate further migration; some must increase in size in the common bile duct. Increased biliary pressure consequently dilates the duct system retrogradely, allowing larger stones to follow. Patients at risk of stone migration and thereby pancreatitis and jaundice have large ducts that can be detected by ultrasound assessment. PMID- 3109636 TI - Probable amniotic fluid embolism precipitated by amniocentesis and treated by exchange transfusion. PMID- 3109637 TI - Danazol and benign intracranial hypertension. PMID- 3109638 TI - Clinical evaluation of lysuride in the management of hyperprolactinaemia. PMID- 3109639 TI - Does atenolol have an effect on calcium metabolism? PMID- 3109640 TI - Successful cadaveric renal transplantation from a donor who died of cyanide poisoning. PMID- 3109641 TI - Screening for cervical cancer: a new scope for general practitioners? Results of the first year of colposcopy in general practice. AB - A survey was carried out over one year of all the women who attended a colposcopy clinic in a general practice. During the year 1254 women underwent cytological screening in the practice and 197 of these underwent colposcopy. Of 79 women with abnormal smears that suggested cervical intraepithelial neoplasia, 62 (79%) were confirmed by biopsy to have cervical premalignancy. In addition, the remaining 118 women with normal or inflammatory smears underwent colposcopy either because of their history or because they requested the investigation. A general underestimate of cervical intraepithelial neoplasia when cytology alone was used was discovered. Seven out of 28 women with inflammatory smears were found to have important cervical premalignancy. Mildly dyskaryotic smears led to a falsely reassuring estimate of the degree of severity of cervical lesions. Seven out of 13 patients who underwent colposcopy because they were thought to be at high risk of neoplasia because of a history of genital warts, unexplained recurrent cystitis, heroin abuse, or immunosuppression had cervical intraepithelial neoplasia proved at biopsy. This report shows that both in screening for and in the follow up of known cervical disease a normal smear cannot guarantee normal pathology. Diagnostic colposcopy is a valuable complementary investigation that could be carried out in a general practice. PMID- 3109642 TI - Benefits and risks of childhood immunisations in developing countries. AB - The ratio of benefit to harm from an imaginary, modest immunisation programme in a developing country and the numbers of lives likely to be saved and severe handicaps prevented have been estimated. Immunisation is much more likely to benefit children than to harm them, and health workers can be confidently encouraged not to withhold the benefits of immunisation from most children. PMID- 3109643 TI - Refusal to treat AIDS and HIV positive patients. PMID- 3109645 TI - Remuneration of Soviet medical personnel. PMID- 3109644 TI - Complacency in diagnosis of cervical cancer. PMID- 3109646 TI - Effectiveness of publicity campaign encouraging earlier referral of hearing loss in adults. AB - During 16,070 consultations in general practice 70 adults complained of difficulty with hearing. A simple poster displayed in the waiting areas together with an accompanying leaflet almost doubled the incidence of presentation of loss of hearing. Nevertheless, more than half of those complaining had failed to notice the prominently displayed personally relevant message, and the beneficial effect was lost almost as soon as the poster was removed. PMID- 3109647 TI - Inequalities and the new Health Education Authority. PMID- 3109648 TI - Inequalities in health in Britain: specific explanations in three Lancashire towns. PMID- 3109649 TI - Effect of protein restriction in insulin dependent diabetics at risk of nephropathy. PMID- 3109650 TI - Infection by airborne Chlamydia trachomatis in a dentist cured with rifampicin after failures with tetracycline and doxycycline. PMID- 3109652 TI - Respiratory health workers visiting patients with chronic respiratory disability. PMID- 3109653 TI - Unemployment and mortality. PMID- 3109651 TI - Pinch skin grafting or porcine dermis in venous ulcers. PMID- 3109654 TI - Fall in intraocular pressure during acute hypocalcemia in patients with insulin dependent diabetes. PMID- 3109655 TI - AIDS and the heterosexual epidemic. PMID- 3109656 TI - Infantile apnoea and home monitoring. PMID- 3109657 TI - Asymptomatic carotid stenosis: spare the knife. PMID- 3109658 TI - Diagnosing pulmonary thromboembolism. PMID- 3109659 TI - Child abuse or copper deficiency? A radiological view. PMID- 3109660 TI - The search for a hormonal switch for obesity. PMID- 3109661 TI - Insulin bolus given by sprinkler needle: effect on absorption and glycaemic response to a meal. AB - Two studies were conducted investigating the effect of injecting short acting insulin subcutaneously by means of a sprinkler needle; this needle has 14 small holes in the wall but is sealed at the tip. In the first study absorption of 8 U iodine-125 labelled Actrapid HM injected subcutaneously at two separate sites in the abdominal wall was measured in 10 patients. One injection was given with the sprinkler needle and the other with a conventional needle. The initial dose absorbed during the first 30 minutes was significantly higher with the sprinkler needle. In the second study 10 U Actrapid HM was given to 11 other patients (all negative for C peptide and with low insulin binding antibody titres) on two separate days immediately before a standardised breakfast either by the sprinkler needle or by a conventional needle (random order). Plasma free insulin increased more rapidly and to higher concentrations with the sprinkler needle and the glycaemic response was considerably diminished. The sprinkler needle improves both the insulin absorption rate and the glycaemic response to a meal and may reduce the 30 minutes or so before meals that diabetics must inject to minimise postprandial hyperglycaemia. PMID- 3109662 TI - What happens to opiate addicts immediately after treatment: a prospective follow up study. AB - In the first British study to investigate systematically what happens to opiate addicts after treatment 50 opiate addicts admitted for inpatient treatment of their drug dependence were followed up for six months after discharge. All had been withdrawn from opiates before follow up. Six months later 26 were not using opiates: 12 had not used opiates at any time since discharge. When subjects in hospital or in prison were excluded from the analysis 21 (47%) of the subjects living in the community were not taking opiates. Many subjects used opiates within days of leaving the inpatient unit, but this first lapse did not necessarily lead to a full relapse into addictive use. During the six months after discharge several subjects used opiates on a less than daily basis. During each two month period throughout the six months of follow up the proportion of subjects who were occasional users fell, the proportion of abstinent subjects grew, and the proportion of daily users (assumed to be readdicted) remained constant. Although many of the addicts relapsed soon after treatment, it was encouraging that almost half were opiate free after six months. These results have important implications for the treatment of drug addicts. PMID- 3109663 TI - Successful treatment of acute mountain sickness with dexamethasone. AB - A double blind, randomised, placebo controlled trial of treatment with dexamethasone for acute mountain sickness was performed in the Capanna "Regina Margherita" at an altitude of 4559 m in the Alps Valais. After 12-16 hours of treatment (8 mg dexamethasone initially, followed by 4 mg every six hours) the mean acute mountain sickness score decreased significantly from 5.4 to 1.3, and eight of 17 patients became totally asymptomatic. Mean arterial oxygen saturation rose from 75.5% to 82.0%, and there was a small increase in standard spirometric measurements. In the placebo group none of these variables changed significantly. It is concluded that dexamethasone may be used as emergency treatment for acute mountain sickness to facilitate safe descent to a lower altitude. PMID- 3109664 TI - Intraregional variation in treatment of end stage renal failure. PMID- 3109665 TI - Loperamide toxicity in a child after a single dose. PMID- 3109666 TI - Verapamil in atrial fibrillation in hyperthyroidism. PMID- 3109667 TI - Persistent mesenteric ischemia in a young woman. PMID- 3109668 TI - Screening for hearing loss in childhood: a study of national practice. AB - A questionnaire survey of all health districts in England and Wales was carried out at the end of 1984 to document screening programmes for identifying hearing loss in childhood. The response rate was 81.3%. All districts performed distraction testing, all but nine aiming at doing so at 7-9 months of age. All districts tested children's hearing at school, generally before 7 years of age. The number of times that children were screened both before school and at school varied considerably, from one to six times before school and one to six times at school. Few districts collected information that would allow them to make judgments about the efficiency of effectiveness of their screening programmes. PMID- 3109669 TI - Chronic ulcer of the leg: clinical history. AB - Six hundred patients with chronic leg ulcers were studied by detailed history and examination as part of a population survey. In 22% ulceration began before the age of 40, and in this group the sex incidence was equal. Over age 40 there was an increasing preponderance of women. Ulcers were significantly more common in the left leg in women but not in men. The site of 26% of ulcers did not include the classical medial goiter area. The median duration of the ulceration at the time of the survey was nine months and 20% had not healed in over two years. The great majority of patients had had recurrence, 66% having had episodes of ulceration for more than five years. Healing of ulcers is a serious problem, but preventing recurrence is the greater challenge. PMID- 3109670 TI - Are combined orthopaedic and rheumatology clinics worth while? AB - The practice of holding combined orthopaedic and rheumatology clinics is widespread, but no attempt has been made to assess their usefulness. In a one year prospective study patients were randomised either to a combined clinic with a rheumatologist and an orthopaedic surgeon or to a clinic with an orthopaedic surgeon alone. The details of the patients' disease, the interview, the surgeons' and rheumatologists' responses, and the patients' opinions were recorded on questionnaires. Interviews were appreciably longer in the combined clinic, and more referrals for surgery were made. The rheumatologist correctly predicted the need for surgery in 95% of cases, and his presence in the clinic was considered desirable by the surgeon, principally when the referral letter was inadequate. It is concluded that most patients with rheumatic diseases can be seen more efficiently in routine orthopaedic clinics provided a good quality letter of referral is sent. PMID- 3109671 TI - Management of Parkinson's disease. PMID- 3109672 TI - A D Waller and the electrocardiogram, 1887. PMID- 3109673 TI - Report from the PHLS Communicable Disease Surveillance Centre. PMID- 3109674 TI - Lichen sclerosus et atrophicus in children misdiagnosed as sexual abuse. PMID- 3109675 TI - Portraits from memory. 14--Professor William John Tulloch (1887- 1966). PMID- 3109676 TI - Ending "forensic blind man's buff". PMID- 3109678 TI - Intensive care: a specialty or a branch of anaesthetics. PMID- 3109677 TI - Laboratory control of oral anticoagulants. PMID- 3109679 TI - Sue's breast lump. PMID- 3109680 TI - A forgotten factor in pelvic inflammatory disease: infection in the male partner. PMID- 3109681 TI - Corticosteroids and bone mass in asthma. PMID- 3109682 TI - Screening for congenital dislocation of the hip. PMID- 3109683 TI - Effect of combined implants of oestradiol and testosterone on libido in postmenopausal women. PMID- 3109684 TI - Auditory rehabilitation: should we listen to the patient? PMID- 3109685 TI - How does the limbic system assist motor learning? A limbic comparator hypothesis. AB - This paper offers a new hypothesis about how the limbic system might assist motor learning. It is proposed that interactions of limbic and sensorimotor-related systems are essential for learning what to do in a motor task (appropriate, relevant behavior) and how to do it best (motor skill). Limbic modulations of sensorimotor-related neural centers are envisaged to result from comparisons in various neural centers of converging inputs from the relevance-sensitive amygdala and from corollary, cortically-modulated recipients of amygdaloid information. Such comparisons of relatively 'raw' limbic inputs and their 'processed', corollary forms could be achieved in a side-loop manner resembling that in the cerebellum. This 'limbic comparator' hypothesis was prompted by studies of motor learning that show how monkeys develop skill only after gaining insight into appropriate, task-related behavior, and that inappropriate behavior during transition into the insightful state produces 'error' signals from the anterior cingulate cortex. Known sites of limbic projections that could serve corollary comparisons are examined with regard to their possible influence on motivation, appropriate, task-related behavior and motor skill. Anatomical and functional tests of convergence and comparison in sensorimotor-related neural centers are suggested in order to stimulate investigations of the limbic comparator hypothesis. PMID- 3109686 TI - A comparative study of the immunohistochemical localization of a presumptive proctolin-like peptide, thyrotropin-releasing hormone and 5-hydroxytryptamine in the rat central nervous system. AB - A proctolin (PROC)-like peptide was studied immunohistochemically in the hypothalamus, lower brainstem and spinal cord of the rat using an antiserum against PROC conjugated to thyroglobulin. Neuronal cell bodies containing PROC like immunoreactivity (PROC-LI) were observed in the dorsomedial, paraventricular and supraoptic nuclei of the hypothalamus and in the nucleus raphe magnus, nucleus raphe pallidus, nucleus raphe obscurus and nucleus interfascicularis nervi hypoglossi in the medulla oblongata. Fibers containing PROC-LI were seen in the median eminence and in other hypothalamic nuclei, and in the lower brainstem in cranial motor nuclei including the dorsal motor nucleus of the vagus nerve, the motor trigeminal nucleus, the facial nucleus and nucleus ambiguous, and in lower numbers in the nucleus of the solitary tract and locus coeruleus. Fibers containing PROC-LI were also located in the spinal cord, in the intermediolateral cell column at thoracic levels and in the ventral horns at all levels of the spinal cord. After transection of the spinal cord, all PROC-immunoreactive fibers below the lesion disappeared. Following injection of Fast blue into the thoracic spinal cord, retrogradely labeled cells in the nuclei raphe pallidus, obscurus and magnus and nucleus interfasciculari nervi hypoglossi were seen to contain PROC-LI. PROC-LI had a similar distribution as thyrotropin-releasing hormone (TRH)-LI in the above-mentioned areas and coexistence of TRH-LI and PROC-LI was shown in cell bodies in the hypothalamus and medulla oblongata. PROC-LI could also be shown to coexist with 5-hydroxytryptamine (5-HT)-LI in neuronal cell bodies in the lower brainstem. The results demonstrate the occurrence of a PROC like peptide in the mammalian nervous system, and these neurons seem to be at least largely identical to previously described TRH systems. A possible involvement of the PROC-like peptide in spinal motor control is discussed in relation to the well-established role of PROC in control of motor behavior in insects and invertebrates. PMID- 3109687 TI - Analgesic properties of valproic acid might be related to activation of pro enkephalin system in rat brain. AB - Recent in vivo and in vitro studies have shown the involvement of gamma aminobutyric acid (GABA) in analgesia. We investigated if the analgesia induced by an acute valproic acid (VPA) administration might be related to the activation of the enkephalinergic system. VPA administration (i.p.) induces 30 min after treatment a significant and dose-dependent increase of Leu-enkephalin and Met enkephalin in the striatum, hypothalamus, cortex and brainstem. In the hypophysis no modification was observed for these two neuropeptides. The Met-enkephalin-Arg Gly-Leu levels are affected by VPA administration in a more complex pattern. Such results suggest the implication of an enkephalinergic system in GABAergic analgesia. PMID- 3109688 TI - Occlusion of hippocampal electrical junctions by intracellular calcium injection. AB - Low-molecular weight dyes such as Lucifer yellow or carboxyfluorescein have been used to investigate the electrical connectivity of neurons via gap junctions. The interpretation that such dye passage is mediated through intercellular channels has been controversial and difficult to corroborate with direct techniques in mammalian brain. We report here that elevated intracellular free Ca2+, a treatment shown to cause gap junction occlusion in other tissues, significantly blocks dye transfer between hippocampal cells. Furthermore, intracellular injection of FITC-dextran (which is too large to cross gap junctions) never resulted in multiple hippocampal cell fills. These data lend strong support to the argument that the extent of dye-coupling provides a good estimate of the number of intercellular communication channels, and raises the possibility that these channels may be physiologically modulated. PMID- 3109689 TI - Evidence for increased activity of mouse brain fatty acid cyclooxygenase following drug-induced convulsions. AB - Enzymatic production of prostaglandins (PGs) from exogenous arachidonic acid was studied in brain microsomal fractions prepared from mice following pentylenetetrazol (PTZ)-induced convulsions. Prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) measured either by radioimmunoassay or after incubation with [1-14C]arachidonic acid (AA) was significantly increased in microsomes from the convulsed animals. Pretreatment of the mice with the anticonvulsant ethosuximide prevented the enhanced PG production. The increased PG synthesis could not be attributed to an increased substrate availability nor to an activated phospholipase nor to a direct effect of the convulsant on the fatty acid cyclooxygenase. Evidence that a modification of the cyclooxygenase had occurred with seizure activity was obtained from kinetic analysis; the apparent Km for the AA was lowered from 30 +/- 3 microM in the controls to 12 +/- 1 microM in the PTZ-treated mice. Further evidence for a modification of the fatty acid cyclooxygenase was obtained from incubations of the microsomes with catalase to reduce peroxide formation. Limiting peroxide levels did not decrease the microsomal cyclooxygenase activity in the PTZ-treated mice to control levels. Seizure activity induced by picrotoxin and strychnine also increased the microsomal capacity of the convulsed animals to synthesize PGs. The increased brain fatty acid cyclooxygenase activity may result from a biochemical modification of the enzyme induced by seizure activity. PMID- 3109690 TI - Stereospecific acute neuronotoxicity of 'uncommon' plant amino acids linked to human motor-system diseases. AB - The L-isomer of beta-N-methylamino-L-alanine (BMAA), present in free form in seed of Cycas circinalis, elicits in spinal cord cultures a pattern of acute postsynaptic neuronal vacuolation comparable to that induced by beta-N oxalylamino-L-alanine (BOAA), an excitotoxic amino acid of greater potency isolated from seed of Lathyrus sativus. The neuronotoxic properties of these compounds may be linked to the etiology of motor-system degenerative disorders (amyotrophic lateral sclerosis and lathyrism, respectively) found in human groups that have used these plant seeds for food. PMID- 3109691 TI - Human amnion membrane as a substratum for cultured peripheral and central nervous system neurons. AB - We report here on the use of human amnion membrane as a substratum for the culture of neuronal cells. Pieces of amnion membrane were bound to nitrocellulose paper as a supporting material, seeded with neurons, and cultured for 1-4 days. Neurons and neurites were visualized after fixation by immunoperoxidase staining using an anti-neurofilament monoclonal antibody. Neurons from embryonic chick ciliary and dorsal root ganglia and fetal rat hippocampus were cultured on either the basement membrane or stromal surface of the amnion membrane. Neurons adhered to both surfaces but extended neurites only on the basement membrane surface. Neurons survived and continued to grow neurites in serum-free medium for at least 4 days. When cultured for 4 days on the basement membrane surface in the presence of 10% fetal calf serum, the ciliary ganglion neurons survived but neurite growth was markedly inhibited, while dorsal root ganglion neurons survived, hypertrophied and grew an extensive network of neurites. Other experiments addressed the question whether the basement membrane surface had an ability to guide growing neurites. Amnion membranes were folded, frozen, cross-sectioned using a cryostat, and placed on the nitrocellulose to give irregular patterns of basement membrane juxtaposed to the collagenous stroma. Ciliary ganglion neurons after 4 days in culture had initiated and extended neurites in patterns which corresponded and were limited to those areas visualized by indirect immunofluorescence staining using anti-laminin antibodies. Thus, in vivo assembled human amnion basement membranes appear to contain signals that both promote and guide neuritic growth from previously axotomized embryonic peripheral and central nervous system neurons. The amnion membrane represents a novel tool for the culture of neuronal cells in vitro and potentially could be used as a neurite-promoting bridging material in vivo for regeneration studies. PMID- 3109692 TI - Paradoxical induction of dopaminergic cells following intravitreal injection of high doses of 6-hydroxydopamine in juvenile carp retina. AB - Histofluorescence studies were conducted on two groups of juvenile carp (body length, 12.7 and 6.6 cm on the average, respectively) during certain periods (3 11 months) of retinal growth, to evaluate the destructive effect of 6 hydroxydopamine on dopaminergic and indoleamine-accumulating cells. Within a certain range of doses (0.1-5.0 micrograms/eye) of the neurotoxin injected intravitreally, it was found to destroy both classes of cells in a dose-dependent manner: more cells disappeared with higher doses. However, a high dose (5-25 micrograms/eye) of the neurotoxin caused paradoxical events in the retina, inducing an appearance of clustered dopaminergic cells with various soma sizes and abnormally high regional density, disturbed laminar organization, and a facilitated growth rate at the retinal margin. A preliminary examination with [3H]thymidine labelling suggests that the high dose of 6-hydroxydopamine may cause severe damage to certain classes of cells including dopaminergic and indoleamine-accumulating cells, and that a metamorphic change of precursor cells (neuroblasts) in the outer nuclear layer is responsible for the induction of such abnormal dopaminergic cells as clusters. PMID- 3109693 TI - [Immunocytochemical demonstration and morphometric study by image analysis of estrogen receptors in carcinoma of the breast: study of 30 cases]. AB - The method described associates on cytological preparations, immunocytochemical reaction, counter-staining, random and morphometrical study by image analysis. It permits the quantification of estrophilin in breast carcinoma and the estimation of the heterogeneity of the tumour staining. PMID- 3109694 TI - [Latency, threshold and frequency selectivity of the crossed medial cochlear efferent pathways]. AB - The efferent innervation of guinea pig cochleas was sectioned medially, at the level of the floor of the fourth ventricle, to study the effects of the crossed part of the medial efferent pathway on the compound action potential (CAP) masking phenomenon. Sectioning reduced CAP masking for a masker level varying with the frequency of the masker and the time elapsed between the masker onset and the probe onset. Functional properties of the crossed part of the medial efferent tracts: latency, thresholds and frequency selectivity, could be deduced from these data. This intensification of the masking phenomenon permitting the improvement of the signal to noise ratio, may thus be attributed to the crossed part of the medial efferent bundle which innervates the outer hair cells. PMID- 3109695 TI - [Muscular regeneration by autograft of in vitro multiplied satellite cells]. AB - We used a free-grafting technique modified from that described by Carlson and Gutmann, to induce an ischemic injury of Extensor Digitorum Longus (EDL) muscle in adult rats. In these muscles, a peripheral rim, three to five muscle fibers thick, survive ischemia whereas the muscle fibers occupying the central part follow a sequential pattern of necrosis, degradation and regeneration. Association of X-irradiation to the experimental injury inhibits mitosis of myogenic cells, thus preventing, the regeneration of the injured fibers. At the 14th postoperative day, the muscle is reduced to a cystic structure. The center of this structure is occupied by a loose fibrinous and collagenic network with a few cellular elements. In vitro multiplied autologous satellite cells, labelled with fluorescent latex beads, were injected back into this preparation. Our results indicate that these cells have retained their myogenic characteristics and are able to reform fully differentiated muscle fibers. PMID- 3109697 TI - [Effect of rifampicin, clofazimine and dapsone in treating 296 cases of multibacillary leprosy]. PMID- 3109696 TI - [Mother's touching behavior with regard to the newborn infant: preliminary cases]. AB - Filmed observations of spontaneous interactions between mothers and their newborn infants were used to quantify the maternal tactile behaviours. These behaviours were analysed in relation to the activity of the newborn infant and the different characteristics of the mother and the newborn infant. PMID- 3109698 TI - [Clinical significance of the anti-Sm antibody]. PMID- 3109699 TI - [Enhancing effect of zinc supplementation on the growth of formula-fed children]. PMID- 3109700 TI - [Epidemiologic examination of the duration of immunity of measles vaccine]. PMID- 3109701 TI - [Laboratory indices for the diagnosis of lead poisoning]. PMID- 3109702 TI - [Diagnostic value of ultrasound in cases of minute tumors in the gallbladder]. PMID- 3109703 TI - [Electron microscopy observations on platelet and normal mononuclear reactions in children with idiopathic thrombopenic purpura]. PMID- 3109704 TI - [Immunoglobulin and T cell immunoactivities as related to the allergic reaction following skin test with lung fluke antigen]. PMID- 3109705 TI - [Effect of camptothecin in the treatment of psoriasis]. PMID- 3109706 TI - [Uses of hybridoma-secreting monoclonal antibodies in parasitic diseases]. PMID- 3109707 TI - [Clinical and ultrastructural study on psoriasis treated by indirubin]. PMID- 3109708 TI - [Prognostic value of the lupus band test in light-protected normal skin of patients with systemic lupus erythematosus]. PMID- 3109709 TI - [Experimental infection with Pneumocystis carinii in mice]. PMID- 3109710 TI - [Effects of 5-hydroxytryptamine on various cardiovascular diseases]. PMID- 3109711 TI - [Value of needle aspiration biopsy in the diagnosis of spinal tumors. Report of 23 cases]. PMID- 3109712 TI - [Metallic vertebral body prosthetic replacement in the treatment of primary thoracic vertebra tumors complicated by paraplegia: long-term follow-up of 8 cases]. PMID- 3109713 TI - [Giant cell tumor of bone treated by cryosurgery with liquid nitrogen. Analysis of 42 cases]. PMID- 3109714 TI - [Diagnosis and treatment of Budd-Chiari syndrome: report of 50 cases]. PMID- 3109715 TI - [Monoclonal antibody SZ-21 to platelet membrane glycoprotein IIIa]. PMID- 3109717 TI - [A preliminary study of 44 cases of myelodysplastic syndrome and proposals for its classification]. PMID- 3109716 TI - [Sensitizing fungi in 116 asthmatic patients]. PMID- 3109718 TI - [Uses of dolichos biflorus agglutinin labelling in studying the relation between gastric carcinoma and intestinal metaplasia]. PMID- 3109719 TI - [Scanning electronmicroscopy study on the morphology of urinary erythrocytes]. PMID- 3109720 TI - [In vitro cultivation of juvenile Ancylostoma duodenale]. PMID- 3109721 TI - [Epidermal Langerhans cells originating from the spleen]. PMID- 3109722 TI - Microincineration and elemental X-ray microanalysis of single Bacillus cereus T spores. AB - Single whole spores of bacillus cereus T were analyzed by scanning electron microscopy and electron microprobe X-ray microanalysis before and after high temperature (600 degrees C) ashing in air. High-temperature ashing consisted of a centripetal oxidation of the spore surface combined with pyrolysis of the spore's interior. Ashing of single spores produced a compact central ash particle, mimicking the much larger unashed spore body in outline but containing craterlike microregions, and a peripheral thin ash film. Ashing mostly eliminated the spore's organic matrix; however, ash residues still gave residual carbon characteristic X-ray counts. Ashing of single spores produced a two-, five-, and six-fold increase of potassium, magnesium, and calcium X-ray intensities, respectively. Iron, although low in actual counts, became detectable after ashing. Phosphorus characteristic X-rays were decreased by 41% after ashing, while volatilization lowered sodium and manganese X-ray intensities by over 80%. High-temperature ashing enhanced element-characteristic X-ray intensities of the non-volatilizable mineral(ized) elements of spores by compacting them into ash residues, more so than by simply abolishing their organic matrix. Microincineration appears a generally useful preconcentration technique for elemental detection and localization in X-ray microanalysis. PMID- 3109723 TI - Isolation of Mycoplasma pneumoniae from respiratory tract specimens in Ontario. PMID- 3109724 TI - Expenditures on health care in British Columbia. PMID- 3109725 TI - Selecting initial therapy for bladder cancer. AB - Progress has been made at both ends of the spectrum of bladder cancer. The introduction and increasing use of effective intravesical agents for both treatment and prophylaxis of tumors limited to the mucosa or lamina propria has reduced the incidence and frequency of subsequent tumors. At the other end of the spectrum--patients with locally extensive bladder cancer--neoadjuvant or initial chemotherapy is producing complete and partial responses. Hopefully this will translate into an improvement in the cure rate. In arriving at a decision regarding treatment for a patient with bladder cancer the urologist integrates information derived from a thorough endoscopic examination of the lower urinary tract (bladder and urethra), complete grading and staging of resected tumor including results of mucosal biopsies from suspicious and normal appearing urothelium, and cytology obtained by bladder irrigation. Treatment also may be influenced by such factors as prior history and treatment of bladder cancer and the patient's age and medical status. Assuming no prior bladder tumor history, endoscopic resection/fulguration followed by intravesical therapy will be used for tumors confined to the mucosa (Ta or Tcis) or lamina propria (TI). Optimally the urologist should resect all evident tumor and incorporate the intravesical agent as prophylaxis. Cytology and endoscopy will monitor the success of this approach. If the patient develops another superficial tumor while receiving prophylaxis another intravesical agent can be delivered, possibly using an intensive treatment schedule. Several agents have demonstrated effectiveness both for treatment and prophylaxis. They include mitomycin C, thiotepa, Adriamycin (doxorubicin), and bacillus Calmette-Guerin. The indications for radical cystectomy are invasion into the bladder muscle, tumor extension into the prostatic ducts or prostatic substance, or persistent tumor after an adequate trial of one or more intravesical agents used in conjunction with endoscopic resection. The escalating complete and partial response rates associated with combination chemotherapy of metastatic bladder cancer has led to the use of these regimens before considering cystectomy for patients with locally extensive bladder cancer, e.g., T3, T4, and N1-2. Downstaging with chemotherapy in this group of poor-risk patients may be preferable to the traditional approach of proceeding with exenterative surgery or full-dose radiation and considering chemotherapy later when metastases are evident. PMID- 3109726 TI - Prospective study on the dose relationship of mitomycin C-induced interstitial pneumonitis. AB - Lung damage after mitomycin C (MMC) was first reported in 1978. Although this side effect has been frequently reported since then, there are no data on dose dependency nor on incidence. Therefore, the authors initiated a prospective study to obtain more data on this subject. Forty-four patients treated with MMC entered the study; 37 were evaluable. All patients were subjected to repeated physical examinations, chest x-rays, chest computed tomography (CT) scan and pulmonary function tests. The results were evaluated per cumulative dose level. None of the patients had clinical pulmonary toxicity develop; one patient had pulmonary changes on CT scan, the significance of which remained unclarified. The world literature on this subject was also reviewed. Based on the combined data of the present study as well as the literature review, the authors concluded that MMC related lung toxicity is a dose-dependent side effect, occurring at cumulative dose levels of 20 mg/m2 or more. The incidence is likely to be less than 10%. PMID- 3109727 TI - Cranial nerve palsy as the presenting feature of secondary plasma cell leukemia. AB - A patient with IgA lambda multiple myeloma (MM) developed plasma cell leukemia (PCL), presenting as oculomotor nerve palsy. The cerebrospinal fluid (CSF) contained plasma cells, which double stained with fluoresceinated anti-IgA and anti-lambda antisera. The palsy was most probably due to meningeal myelomatosis. The neurologic disorder appeared to be refractory to the therapy used, although plasma cells disappeared from the peripheral blood. Secondary plasma cell leukemia is a rare complication of MM, usually occurring in the terminal stage of the disease. Those patients may be eligible for central nervous system (CNS) prophylaxis, as is commonly performed in patients with other types of leukemia. PMID- 3109728 TI - Cytotoxic activity of a polyamine analogue, monoaziridinylputrescine, against the PC-3 human prostatic carcinoma cell line. AB - We have previously demonstrated that prostate and prostate-derived rodent tumors can be manipulated into increasing their accumulation of radiolabeled putrescine by alpha-difluoromethylornithine (DFMO)-induced depletion of intracellular putrescine and spermidine. As methods which increase intracellular accumulation of cytotoxic agents often increase the chemotherapeutic effectiveness of the agent, we examined whether an alkylating derivative of putrescine would be cytotoxic to tumor cells. We present here our findings on the cytotoxicity of the aziridinyl derivative of putrescine (AZP) against prostatic cancer cells. The apparent Km for putrescine was 2.5 microM with or without DFMO pretreatment and the apparent Ki for AZP was 1 microM with or without DFMO pretreatment. Intracellular polyamine depletion by DFMO pretreatment resulted in a 3.7-fold greater accumulation of AZP compared to non-DFMO-treated cells. The growth inhibitory activity of AZP was increased with prior polyamine depletion by DFMO with the 50% effective dose decreasing from 18 microM to 2.1 microM. Putrescine was able to block the cytotoxic effect of AZP. Putrescine was also able to rescue the AZP-treated PC-3 cells for up to 6 h following a 1-h exposure to AZP. It appears that aziridinylputrescine behaves like putrescine in that it competes with putrescine for uptake into the cell and, like putrescine, has its uptake into the cell increased by prior polyamine depletion. It differs from putrescine in that it expresses cytotoxic activity and inhibits the growth of the human prostate-derived PC-3 cell line. This cytotoxic activity is also increased by prior polyamine depletion. The cytotoxic behavior of AZP is dependent both on the concentration and duration of exposure. Putrescine can rescue the cells from the effect of AZP. AZP is a potentially useful cytotoxic analogue that utilizes the polyamine transport system for its uptake into the cell. PMID- 3109729 TI - Effect of prostaglandin E2-producing nonmetastatic Lewis lung carcinoma cells on the migration of prostaglandin E2-responsive metastatic Lewis lung carcinoma cells. AB - The role of prostaglandin E2 (PGE2) in directly stimulating metastatic spread by Lewis lung carcinoma (LLC) cells was examined with the use of an in vitro migration model for tumor dissemination. The extent to which cloned metastatic and nonmetastatic LLC cells migrated out of glass capillary tubes in vitro reflected their capacity to form pulmonary metastases in vivo. The addition of PGE2 to metastatic LLC cells further stimulated their migration. Other cyclooxygenase products, besides PGE2, did not stimulate the migration of metastatic LLC cells. Nonmetastatic LLC cells did not migrate out of capillary tubes, even in the presence of exogenous PGE2. The amount of PGE2 secreted by cloned LLC cells was quantitated by a radioimmunoassay. Nonmetastatic LLC cells secreted more PGE2 than did the metastatic LLC cells. When the nonmetastatic LLC cells were either mixed with or placed adjacent to cloned metastatic LLC cells, the migration by the metastatic LLC cells was stimulated. The migration stimulatory capacity of the nonmetastatic LLC cells was minimized in the presence of indomethacin, a prostaglandin synthesis inhibitor. Studies were conducted to relate these in vitro results to tumor metastasis in vivo. Injection of a mixture of metastatic and nonmetastatic LLC cells into mice s.c. resulted in a greater number of lung metastases than did injection of metastatic cells alone. This increase in metastasis formation was prevented by indomethacin. Formation of pulmonary metastases was also augmented when irradiated nonmetastatic LLC cells were injected into metastatic LLC-bearing mice. The results of our studies suggest that nonmetastatic LLC cells, by producing PGE2, can augment in vitro migration and in vivo dissemination of metastatic LLC cells. Thus, the response of tumor cells to PGE2, rather than simply their production of PGE2, appears to be important in regulating tumor dissemination. PMID- 3109731 TI - Effect of hyperthermia (45 degrees C) on calcium flux in Chinese hamster ovary HA 1 fibroblasts and its potential role in cytotoxicity and heat resistance. AB - Hyperthermia caused a major increase in uptake of 45Ca2+ into Chinese hamster ovary HA-1 cells. Increased permeability to Ca2+ was observed with heating periods as brief as 45 degrees C for 4 min and reached a maximum at 45 degrees C for 30 min. In addition to elevation of Ca2+ influx, heat induced an increase in 45Ca2+ exchange with the extracellular Ca2+ pool. The effect of heat on Ca2+ permeability was transient, and Ca2+ influx returned to normal values by approximately 9 h at 37 degrees C. Comparison of the time courses of increased Ca2+ permeability and cell inactivation at 45 degrees C indicated that the heating time required for maximum permeability to Ca2+ was similar to the initial resistant "shoulder" period of the cell survival curve. This suggests that Ca2+ could play a permissive role in thermal cell inactivation; efficient cell killing may require a threshold concentration of intracellular Ca2+. The kinetics of heat induced increase in Ca2+ permeability also resembled that for the induction of thermotolerance. This might suggest a messenger role for Ca2+ in thermotolerance induction. Direct increase in cellular Ca2+ levels with Ca2+ ionophore A23187 (5 X 10(-6) M) led to subsequent heat resistance. However, the heat resistance produced by A23187 was of a lesser magnitude than heat-induced thermotolerance. In addition, A23187 did not induce the stress protein species characteristic of thermotolerance (heat shock proteins), but instead led to the synthesis of a related set of proteins (glucose-regulated proteins). The data thus suggest a role for Ca2+ in the cellular effects of hyperthermia. They are also of potential clinical relevance in that cellular responses to heat might be modified pharmacologically, by the judicious use of Ca2+ active agents, such as Ca2+ ionophores and channel blockers. PMID- 3109730 TI - Benzo(e)pyrene-induced alterations in the binding of benzo(a)pyrene and 7,12 dimethylbenz(a)anthracene to DNA in Sencar mouse epidermis. AB - Benzo(e)pyrene [B(e)P] cotreatment slightly increases the tumor-initiating activity of benzo(a)pyrene [B(a)P] and greatly decreases the tumor-initiating activity of 7,12-dimethylbenz(a)anthracene (DMBA) in Sencar mice (DiGiovanni et al., Carcinogenesis 3: 371-375, 1982). The effects of B(e)P on the binding of B(a)P and DMBA to Sencar mouse epidermis were investigated using a protocol similar to the mouse skin tumorigenicity studies. After 12 h of exposure to 50 nmol [3H]B(a)P and low or high doses of B(e)P, the level of [3H]B(a)P bound to mouse epidermal DNA increased by 30%. However, after 24 h exposure to 50 nmol [3H]B(a)P and after 12 or 24 h of exposure to 200 nmol [3H]B(a)P, B(e)P had no effect on the amount of [3H]B(a)P bound to DNA. The ration of anti-(the isomer with the epoxide and benzylic hydroxyl on opposite faces of the molecule) B(a)P 7,8-diol-9,10-epoxide [B(a)PDE]-deoxyribonucleoside adducts to syn- (the isomer with the epoxide and benzylic hydroxyl on the same face of the molecule) B(a)PDE deoxyribonucleoside adducts did not change at either initiating dose of B(a)P or at any time regardless of the dose of B(e)P. After 12 h of exposure to high doses of B(e)P and a 50-nmol initiating dose of B(a)P the level of [3H]B(a)P bound to DNA increased but there was no change in the proportion of particular B(a)PDE deoxyribonucleoside adducts present. In contrast, B(e)P inhibited the binding of initiating doses of DMBA (5 and 20 nmol) to DNA after 12 and 48 h of exposure to all dose ratios of B(e)P:DMBA tested. The three major adducts, tentatively identified as anti-DMBA-3,4-diol-1,2-epoxide (DMBADE):deoxyguanosine, syn DMBADE:deoxyadenosine and anti-DMBADE:deoxyadenosine, decreased to the same relative extent as the dose of B(e)P increased. Thus, the effects of B(e)P on the total binding of these hydrocarbons to DNA in epidermis correlate with the cocarcinogenic and anticarcinogenic effects of B(e)P on B(a)P and DMBA, respectively, in a mouse skin initiation-promotion assay. These results indicate that the mechanism of the co- or anticarcinogenic action of hydrocarbons such as B(e)P involves alteration of the binding of carcinogenic hydrocarbons to DNA. They also suggest that measurement of carcinogenic hydrocarbon-DNA adducts formed during cotreatment with other hydrocarbons will provide a rapid method for predicting the co- or anticarcinogenic effect of the other hydrocarbons. PMID- 3109732 TI - Evidence for two independent pathways of biologically effective excision repair from its rate and extent in cells cultured from sun-sensitive humans. AB - Repair-proficient human cells can be sensitized to exposure to UV radiation at 254 nm by postirradiation incubation in the presence of the eukaryotic alpha polymerase inhibitor, aphidicolin. The degree of sensitization has been examined in cells cultured from humans suffering from various types of sun-sensitive syndromes. Xeroderma pigmentosum (XP) variant and Bloom's cell lines (both excision proficient) were strongly sensitized by aphidicolin. An excision repair proficient Cockayne's cell line and a deficient XPD line were both sensitized to a level similar to the sensitivity of excision deficient XPA cells. In contrast, three XPC cell lines which show intermediate UV-induced repair replication and UV sensitivity were sensitized little (in one case) or not at all (in two cases) to UV by postirradiation inhibition of the alpha polymerase. These results lead us to conclude that there are two independent pathways of biologically effective excision repair, the major one of which involves the alpha polymerase and a second, less efficient and slower pathway which is independent of the alpha polymerase and which is the only pathway operating in two of the three XPC strains tested. The rates of biologically effective excision repair were similar in normal, XP variant, and Cockayne's cell lines, but these rates were considerably higher than published rates of dimer excision measured under similar conditions. PMID- 3109733 TI - Characterization of skin tumor promotion and progression by chrysarobin in SENCAR mice. AB - The characteristics of the skin tumor promotion response with anthrone derivatives has been further examined in SENCAR mice. Chrysarobin (1,8-dihydroxy 3-methyl-9-anthrone) was an effective skin tumor promoter when applied twice weekly with dose-dependent increases in both papillomas and squamous cell carcinomas between 25 and 100 nmol/mouse. A similar dose-response relationship for papilloma and carcinoma formation was observed when chrysarobin was applied once weekly. Interestingly, chrysarobin was approximately twice as active as a skin tumor promoter when applied once weekly versus twice weekly. Doses of 25,100, and 220 nmol/mouse gave maximal papilloma responses of 2.90, 8.15, and 9.38 versus 0.73, 4.70, and 5.42 papillomas/mouse, respectively, in mice initiated with 25 nmol 7,12-dimethylbenz(a)anthracene. Thus, unlike 12-O tetradecanoylphorbol-13-acetate (TPA), where a twice weekly application frequency is optimal, application of anthrone promoters such as chrysarobin once weekly is a more optimal frequency for papilloma development. Chrysarobin was also a much more effective skin tumor promoter when the start of promotion was delayed by an additional 10 weeks. Thus, groups of mice initiated with 10 nmol 7,12 dimethylbenz(a)anthracene and having promotion started in either the 3rd or the 13th week after initiation had maximal responses of 5.6 or 11.0 papillomas/mouse, respectively. In addition, the rate of papilloma development was faster in the delayed promotion group. The progression of papillomas to carcinomas was examined in all chrysarobin-treated groups and compared with three groups of mice treated with 3.4 nmol TPA. After 60 weeks of promotion, the anthrone promoter-treated groups had carcinoma:papilloma ratios 2.5 to 5.0 times higher than the TPA treated groups. This was due primarily to the fact that similar carcinoma responses were observed in both anthrone- and TPA-treated mice at optimal promoting doses whereas the papilloma responses were significantly lower in the former groups. The data suggest that anthrone derivatives are very efficient tumor promoters. The results are further discussed in terms of mechanisms of skin tumor promotion. PMID- 3109734 TI - Loss of a Hu-ets-1 allele in human leukemia cell lines ML-1, -2, and -3 with a chromosome change at 11q24. AB - The ML cell lines (ML-1, -2, and -3) were derived from the cells of a patient with T-cell malignant lymphoma who developed acute myeloblastic leukemia and whose cells showed a primary chromosome change at band 11q24. Surface marker studies of the ML cells showed that they had both myeloid (MCS-1, MCS-2, and OKM 1) and some T-lymphocyte (3A1/Leu-9 and OKT-4/Leu-3a) characteristics. Molecular studies on these lines were performed in order to determine the possible involvement of the Hu-ets-1 gene, since it is located at band 11q23----q24. All ML cell lines showed half the intensity of the Hu-ets-1 DNA bands as compared to those of controls (karyotypically normal B-cell lines). In contrast, DNAs from leukemia cells with t(4;11)(q21;q23) or t(1;11)(q21;q23 or q24) showed no rearrangement, deletion, or amplification of the ets-1 gene. These findings indicate that a chromosome region (11q24----qter), including the Hu-ets-1 gene, of the ML cells is deleted as a result of the primary cytogenetic change and that heterogeneity is present in the mechanism of human leukemia involving the 11q23-- -q24 region. PMID- 3109735 TI - Induction of tumoricidal activity in isolated rat liver macrophages by liposomes containing recombinant rat gamma-interferon supplemented with lipopolysaccharide or muramyldipeptide. AB - We examined whether the macrophages in the liver, Kupffer cells, could be activated to a tumoricidal state in a similar way as has been described for other macrophage types. Kupffer cells were isolated by centrifugal elutriation of pronase-treated rat livers. Incubation with highly purified recombinant rat gamma interferon in combination with small amounts of lipopolysaccharide or muramyldipeptide resulted in highly cytotoxic macrophages, as measured against P815 tumor cells in an 18 h 51Cr-release assay. Incubation of Kupffer cells with the stimulators entrapped within liposomes, caused phagocytosis of the liposomes and subsequent activation to tumor cytotoxicity, provided that both rat gamma interferon and subthreshold doses of either lipopolysaccharide or muramyldipeptide were encapsulated. The minimum amount of liposomal rat gamma interferon that induced optimal activation was 0.5 U/ml, while 6 ng/ml of liposomal lipopolysaccharide or muramyldipeptide was required. Cytotoxicity of Kupffer cells activated in this way, persisted for at least 48 h. Since liposomes in circulation are readily cleared by the liver macrophages, these findings may have therapeutic implications. PMID- 3109736 TI - Augmentation of the generation of cell-mediated cytotoxicity in culture by mitomycin C. AB - The effects of mitomycin C (MMC) on the generation of cell-mediated cytotoxicity in primary stimulation culture of human peripheral blood mononuclear cells (PBM) with the B lymphoblastoid Raji cell line were assessed. The cell-mediated cytotoxicity induced in culture was significantly augmented when MMC was added to cultures on day -1 to day 3 for 24 h at concentrations of 2.5 X 10(-2) micrograms/ml and 2.5 X 10(-3) micrograms/ml. To identify the cell populations affected by MMC, PBM were separated by adherence to plastic after treatment with MMC for 24 h (day -1). The two populations were recombined with untreated separated cells and stimulated with antigen. The ability to develop an augmented cell-mediated cytotoxicity was associated with the adherent cell fraction of MMC treated PBM. Therefore, the ability of MMC-treated adherent cells to produce interleukin 1 (IL 1) was examined. Significantly higher levels of IL 1 were produced by treated cells as compared to untreated adherent cells. The results appear to indicate that the selective effects of MMC on the adherent cell fraction, especially the modification of IL 1 production, may be involved in the mechanisms of MMC-induced augmented cell-mediated cytotoxicity. PMID- 3109737 TI - Subcutaneous recombinant gamma interferon in cancer patients: toxicity, pharmacokinetics, and immunomodulatory effects. AB - Recombinant gamma interferon (r gamma-IFN) was administered s.c. daily to 26 patients with advanced cancer. Patients were assigned to one of six doses: 0.5, 1, 2, 4, 6, or 8 million units (MU)/m2 per d. The major toxicities were an influenza-like syndrome and fever, seen in all patients. Dose limiting toxicity occurred in 4 of 4 patients treated at 8 MU/m2. One patient with nodular poorly differentiated lymphocytic lymphoma had a mixed response, and two patients with renal cell cancer have had stabilization of disease for greater than 10 and greater than 12 months. Pharmacokinetic analysis, by radioimmunoassay, revealed mean serum r gamma-IFN concentrations up to 17 ng/ml, with maximal serum levels noted 6 to 13 h after injection. In vivo immunomodulation was assessed by natural killer (NK) cytotoxicity, monocyte activation as determined by cell surface expression of HLA-Dr, and peripheral blood mononuclear cell phenotype analysis by flow cytometry. The mean T4/T8 ratio increased from 2.1 pretreatment to 4.1 after 24 h of treatment, but returned to baseline after 7 and 28 days of treatment. Augmentation of NK function was noted after 7 days of treatment. Monocyte cell surface expression of HLA-Dr increased after 28 days of treatment at the three lowest doses. In conclusion, daily s.c. r gamma-IFN can be easily administered on an outpatient basis with minimal local skin toxicity, results in prolonged serum levels, and is associated with immunological changes of potential antitumor significance. Further study of the in vivo immunomodulatory effects induced by r gamma-IFN is indicated to help define the optimal treatment regimen. PMID- 3109738 TI - A phase I study of recombinant interferon gamma administered by s.c. injection three times per week in patients with solid tumours. AB - Human recombinant DNA interferon gamma (IFN-G), with a specific activity of 2 X 10(6) IU/mg protein, was administered s.c. 3 days per week for 2 months to patients with solid tumors. The maximum tolerated dose (MTD) was 10 X 10(6) IU/m2 (5.0 mg/m2) per injection, and six patients were treated at the MTD. Two of these ceased treatment because of severe subjective toxicity (headache, rigors and pyrexia) and three patients developed WHO grade 3 leucopenia. Subjective toxicity varied considerably between patients and some patients at low dose levels experienced severe constitutional symptoms whilst others treated at the MTD had few side effects. These differences were unrelated to pharmacokinetic parameters. Bioavailability of this IFN-G administered s.c. was very variable from one patient to another at the same dose level. We therefore counsel caution in using this IFN-G preparation s.c. in phase II studies. PMID- 3109739 TI - Modification of natural killer activity of lymphocytes infiltrating human lung cancers. AB - The purpose of these studies was to compare local and systemic human lymphokine activated killer (LAK) and natural killer (NK) cytotoxic activity and to determine its modulation by biologic agents. Local immunity may be an important component in limiting local tumor growth. Therefore, as a model for studying immune function in the local compartment, we assessed NK activity of lymphocytes present at the site of human tumors and in peripheral blood (PBL). We extracted tumor infiltrating lymphocytes (TIL) and PBL from patients with pulmonary tumors and compared NK activity and response to the biological modifiers gamma interferon (IFN-gamma), indomethacin (INDO), and interleukin 2 (IL-2). We also studied TIL and PBL LAK activity using the NK-resistant M14 target cells and determined the TIL response to IL-2, plus IFN-gamma. Titration of K562 targets in a 51Cr release assay revealed that untreated TIL have low cytotoxicity (4.32%) compared to untreated PBL (34.3%, P = less than 0.001). This low level of TIL NK activity was not affected by IFN-gamma, INDO, or IL-2 at 1 h. However, at 3 days of culture, IL-2 with or without exogenous IFN-gamma significantly increased TIL NK cytotoxicity (20.5%, P = 0.02 without IFN-gamma and 32.52 lytic units (LU), P = less than 0.02 with IFN-gamma). Untreated TIL and PBL both had low cytotoxicity against M14 targets (1.08 LU and 1.26 LU), respectively. After 3 days culture with IL-2 plus IFN-gamma, both TIL and PBL LAK cytotoxicity were increased (14.34 LU and 40.63 LU). We conclude that local NK and LAK activity is intrinsically low. However, this activity can be modulated by biologic agents, thus giving hope for the development of local anti-tumor effectors capable of in vivo tumor control. PMID- 3109740 TI - [Prognostic significance of acute nitrate administration in the preoperative evaluation of patients with post-infarct left ventricular aneurysm]. PMID- 3109741 TI - Quantitative validation of cineangiographic axial oblique biplane left ventricular volume measurement. AB - Axial oblique left ventriculography allows unique visualization of acquired and congenital cardiac lesions. However, validation of the accuracy of left ventricular (LV) volume with axial oblique projections is limited and clouded by orthogonal violations between biplane projections. Biplane cineradiographic volume measurement of 17 LV casts employing the axial projection 35 degrees right anterior oblique/55 degrees left anterior oblique/30 degrees cranial (35 degrees RAO/55 degrees LAO/30 degrees Cr) was performed and compared to the conventional postero-anterior/lateral (PA/Lat) and 30 degrees right anterior oblique/60 degrees left anterior oblique (30 degrees RAO/60 degrees LAO) views. LV volume was calculated from biplane cineradiograms by area length and Simpson's rule method. True LV volume by water displacement was 33 +/- 28 (mean +/- S.D.), range 15 to 112 ml. LV cast volume calculated by the area length method from cineradiograms was overestimated (p less than 0.002) but no different by Simpson's rule method (pNS). The ideal correlation was best approximated by the 35 degrees RAO/55 degrees LAO/30 degrees Cr biplane view calculated by Simpson's rule, r = 0.99, y = 3.5 + 0.9x, and standard error of estimate (SEE) = 4.3 ml. Biplane LV angiography with the axial projection permitted accurate LV volume measurement, and Simpson's rule provided the best representation of true volume. PMID- 3109742 TI - Synthesis of angiotensins by cultured granuloma macrophages in murine schistosomiasis mansoni. AB - Components of the angiotensin system are present in granulomas of murine schistosomiasis mansoni. Angiotensins may have immunoregulatory function. Granuloma macrophages cultured for up to 3 days generated substantial angiotensin I (AI) and angiotensin II (AII) which appeared in the culture supernatants. Macrophage monolayers were incubated with 3H-labeled amino acids, and culture supernatants were extracted with acetone and analyzed by HPLC. Radiolabeled products eluted at times corresponding to those of authentic angiotensins. Immunoadsorption of angiotensins with angiotensin antisera removed reputed radiolabeled angiotensins from the supernatants. Treatment of the elution fraction corresponding to that of authentic AI with angiotensin-converting enzyme resulted in the generation of radiolabeled polypeptides which coeluted with authentic AII and His-Leu. Similar experiments conducted with nonadherent granuloma cells devoid of macrophages failed to demonstrate angiotensin production. These results suggest that granuloma macrophages can synthesize angiotensins. PMID- 3109743 TI - Epithelioid cell granuloma induction in the guinea pig by haptenated Mycobacterium leprae. AB - Fluorescein isothiocyanate (FITC)-conjugated Mycobacterium leprae (FITC-M. leprae) was injected intradermally into the ears of guinea pigs and granuloma formation in the draining postauricular lymph nodes was studied. At 2 weeks, there was an increase in weights and infiltration of the draining lymph nodes in half of the animals injected with FITC-M. leprae. At 5 weeks, there was a significant increase in the weights and infiltration of these draining lymph nodes in the guinea pigs injected with haptenated M. leprae compared with those injected with unconjugated M. leprae. At 5 weeks, there was also a significant increase in delayed type hypersensitivity responses to 25 micrograms purified protein derivative. Histologically, epithelioid cell granulomas were seen in these lymph nodes as early as 2 weeks when FITC-M. leprae was used as the source of antigen. Enhancement in the immunogenicity of M. leprae by conjugation with FITC has been postulated. PMID- 3109744 TI - Macrophage activation factor from EL-4, a murine T-cell line: antigenic characterization by hamster monoclonal antibodies to murine interferon-gamma. AB - A cloned variant of the EL-4 murine T-cell line treated with phorbol myristate acetate (PMA) releases a factor that activates macrophages for nonspecific tumor cytotoxicity. This macrophage activation factor (MAF) is both physicochemically (Mr 25,000; pH 2 stable) and biologically different from interferon-gamma (IFN gamma). However, EL-4 MAF may represent a breakdown product or otherwise altered fragment of IFN-gamma. We examined this possibility with a unique pair of hamster monoclonal antibodies against different epitopes of murine IFN-gamma. Both antibodies inhibited IFN-gamma-induced fibroblast antiviral activity; H21 but not H1 antibody also inhibited lymphokine (LK)-induced macrophage-mediated tumor cytotoxicity. Neither antibody, however, had any effect on the EL-4 MAF throughout a broad dose response. Moreover, passage through a H21 immunoaffinity chromatography column or addition of staphylococcal protein A and antibody completely inhibited LK-induced macrophage tumoricidal activity but did not affect the activity in EL-4 MAF. Identical effects in both fluid and solid phase were observed with polyclonal rabbit antisera to murine IFN-gamma. Results with all of these antibodies strongly suggest that the EL-4 MAF and murine IFN-gamma are antigenically distinct. PMID- 3109745 TI - Regulation of B-lymphocyte production in the bone marrow: mediation of the effects of exogenous stimulants by adoptively transferred spleen cells. AB - The cellular mechanism by which an injection of sheep red blood cells (SRBC) results in an increased production of B lymphocytes in mouse bone marrow has been studied by adoptive cell transfer and the use of two in vivo assays of bone marrow B-cell genesis. Proliferation of B progenitor cells was examined by immunofluorescent labeling combined with mitotic arrest, while small lymphocyte renewal was measured by [3H]thymidine labeling and radioautography. In C3H/HeJ mice the administration of SRBC resulted in increased proliferation among bone marrow pre-B cells which contained cytoplasmic mu heavy chains but lacked kappa light chains and surface mu chains. The turnover of small lymphocytes also increased. These stimulatory effects were transferred to naive recipient mice by organ fragments and by cell suspensions harvested from the spleens of donor mice injected with SRBC. In contrast, spleen cells and thymus cells from saline injected donors and thymus cells from SRBC-injected donors had no such stimulatory effects. The results demonstrate that spleen cells mediate the stimulatory effect of SRBC on bone marrow B-lymphocyte production. Spleen cell transfer provides a system to study further the cells and factors involved in the regulation by external environmental agents of the rate of primary B-cell genesis in vivo. PMID- 3109746 TI - Class II antigen-specific murine cytolytic T lymphocytes (CTL). I. Analysis of bulk populations and establishment of Lyt-2+L3T4- and Lyt-2-L3T4+ bulk CTL lines. AB - Murine allogeneic cytolytic T lymphocytes (CTLs), including long-term bulk CTL lines, were induced in I-region-incompatible combinations of strains in vitro in order to study the phenotypes of class II major histocompatibility complex (MHC) antigen-specific CTLs, as well as the possible functional involvement of accessory cell interaction molecules such as Lyt-2 and L3T4. This report shows that class II-specific allogeneic CTL populations consist of two types of T cells. Lyt-2+L3T4- (2+4-) and Lyt-2-L3T4+ (2-4+), in variable proportions depending on the strain combination, that in vitro bulk CTL lines with each of these phenotypes can be established, that the killing function of 2-4+ CTL is sensitive to the blocking effect of anti-L3T4 antibodies, suggesting functional involvement of this molecule in the CTL-target interaction, that anti-Lyt-2 antibodies fail to block killing by 2+4- cells, suggesting that such CTLs do not utilize this molecule in their killing function, and that while I-A-specific CTLs of both phenotypes are detectable, 2-4+ cells could not be detected among I-E specific CTL populations. PMID- 3109747 TI - Human monocyte eicosanoid production: differential rates of metabolite release. PMID- 3109748 TI - [Oxygen consumption, carbon dioxide production and the respiratory quotient in infants]. PMID- 3109749 TI - Evaluation of cefotaxime concentrations in rat cerebral areas and serum by microbiological method and HPLC. AB - The aim of the investigation was to verify the reliability and sensitivity of High Performance Liquid Chromatography (HPLC), compared to the classic microbiological method of plate diffusion, in evaluating cefotaxime concentrations in some cerebral areas and serum of the rat. The mean concentration of cefotaxime in the serum (after acute administration of 15 mg/kg i.m.) was 20 micrograms/ml with the microbiological method and 23 micrograms/ml with HPLC. No antibiotic was detectable, with both methods, in the cerebral areas. The results with both methods are in good accordance, although the HPLC technique is more sensitive and accurate. PMID- 3109750 TI - Sensitivity to rifaximin and rifampicin of Mycobacterium tuberculosis isolated from guinea pigs treated orally with rifaximin. AB - The in vitro sensitivity of the H 37 RV strain of Mycobacterium tuberculosis to rifaximin and rifampicin was determined by evaluating both the antimycobacterial activity of the two rifamycin derivatives after oral administration to infected guinea pigs and the influence of rifaximin on the susceptibility to rifampicin of the isolated strain from spleen, lungs and liver. The results showed that after oral treatment with rifaximin no changes regarding the sensitivity of the strain to rifaximin and rifampicin were seen. PMID- 3109751 TI - Urinary schistosomiasis acquired in Mali, West Africa. I. Case report of Schistosoma haematobium infection in a Sri Lankan with a note on the parasitic life cycle and the risk of local transmission. PMID- 3109752 TI - Urinary schistosomiasis acquired in Mali, West Africa. II. Investigation of returnees exposed to risk environment. PMID- 3109753 TI - Effects of recombinant human interferon-gamma (Met-Gln form) on expression of Fc receptor and Ia-like antigen on human peripheral monocytes and lymphocytes: a comparative study with natural human interferon-alpha and -beta. PMID- 3109754 TI - Enhancement of Ia-like antigen expression by interferon-gamma in polymorphonuclear leukocytes. PMID- 3109755 TI - Spectroscopic studies on double-stranded poly d[(G-C)(G-C)] in B and Z form after covalent modification with the anti diastereomer of trans-7,8-dihydroxy-9,10 epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. AB - Poly d[(G-C)(G-C)] in B or Z conformation has been incubated with the anti diastereomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE). Enzymatic hydrolysis, circular dichroism (CD) and light absorption were used to study the binding specificity of anti-BPDE to the right- and left handed forms of poly d[(G-C)(G-C)]. The effect of anti-BPDE binding on the conformational transition, induced by MnCl2 or NaCl, was also studied. The results obtained demonstrate that in Mn2+-containing solutions, when the ionic conditions are identical, there is only a minor difference in the extent of covalent binding of anti-BPDE to the polynucleotide in right- or left-handed form. A high degree of enantioselectivity of poly d[(G-C)(G-C)] towards (+)-anti BPDE was observed with both conformational states, although the B form seems to be slightly more selective. With either form, the major adduct in the h.p.l.c. analysis is consistent with trans-N2-10-[(7 beta,8 alpha,9 alpha-trihydroxy 7,8,9,10- tetrahydrobenzo[a]pyrene)-yl]-deoxyguanosine [(+)-anti-BPDE-N2-dG] adducts. A 3 nm bathochromic shift of the light absorption of the pyrene chromophore was observed for the Mn2+-induced left-handed form of the polynucleotide. A similar shift was observed with the NaCl-induced transition only at intermediate NaCl concentrations, where the CD spectra showed a mixture of right- and left-handed forms. The bathochromic shift may be a consequence of a reduced exposure of the chromophore to the aqueous solvent. In poly d[(G-C)(G-C)] modified with anti-BPDE, higher ionic strengths are required to reach optimal B-Z transition compared to unmodified samples. This indicates that there is a restriction in the transition process at the sites of modification. The results have been discussed in terms of two distinct domains in the modified polynucleotide: one 'normal' domain, where an initially rapid transition takes place, and another 'BPDE-domain' involving the modification site and a few adjacent base pairs. It is likely that this domain is associated with the inhibitory effect on the B-Z transition. PMID- 3109756 TI - Properties of covalent benzo[a]pyrene diol epoxide-DNA adducts investigated by fluorescence techniques. AB - The spectroscopic absorption and fluorescence properties of adducts derived from the covalent binding of (+/-)trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10 tetrahydrobenzo[a]pyre ne (BPDE) to DNA are re-examined in view of conflicting interpretations regarding the conformations of these adducts which currently exist in the literature. The fluorescence decay profiles were accurately determined utilizing synchrotron-pulsed light source excitation and the time correlated single photon counting technique. The conformational properties of the adducts were probed by determining their accessibilities to acrylamide, a known fluorescence quencher, and by comparing the accessibilities of the BPDE-DNA adducts with those of known model systems with intercalative, partially intercalative and minor groove binding conformations. In contrast to any of these model systems, the fluorescence of the aromatic pyrenyl residues in the covalent BPDE-DNA adducts exhibit significant sensitivity to acrylamide, suggesting that these residues are located at binding sites with significant solvent exposure. A quantitative analysis of the acrylamide fluorescence quenching according to a dynamic Stern-Volmer quenching model suggests the following characteristics: the major (65%) component (1.4 ns lifetime) is characterized by significant exposure to the solvent environment; the second component (6-7 ns lifetime) can be subdivided into a solvent-accessible and a solvent-inaccessible component, the inaccessible fraction being attributed to minor adducts, possibly with a quasi intercalative conformation. The amplitude of the third, long-lived (200-ns) component is variable; it arises from the photochemical decomposition of the adducts which gives rise to tetraols (7,8,9,10-tetrahydro tetrahydroxybenzo[a]pyrene). The variable content of these degradation products accounts for most discrepancies in the fluorescence properties of the covalent BPDE-DNA adducts previously reported. PMID- 3109757 TI - Induction of morphological transformation and micronuclei in Syrian hamster embryo fibroblasts by 1,2-dioxetanes. Correlation with single-strand breaks in HL 60 cells. AB - The photochemical genotoxic and cell-transforming potential of 4-hydroxymethyl 3,3,4-trimethyl-1,2-dioxetane (HTMD) and 3-(N-[4-pyridino]carbamoyl)methyl-3,4,4 trimethyl-1,2-dioxetane , (APD), in mammalian cell was studied. Both dioxetanes, which are efficient sources of triplet-excited ketones on thermal decomposition, induced morphological transformation in Syrian hamster embryo (SHE) fibroblasts. Unscheduled DNA synthesis in SHE and in HeLa cells could not be detected with these dioxetanes, but the number of micronuclei scored after the first mitosis was dose-dependently increased. Single-strand breaks but not Micrococcus luteus u.v.-endonuclease sensitive sites were observed by alkaline elution in HL-60 cells when treated with sub-lethal doses of HTMD and APD. A possible mechanism for the transformation mediated by DNA and chromosomal damage as well as the intermediacy of triplet carbonyls in these events are discussed. PMID- 3109758 TI - The metabolism of indole alkaloid tumor promoter, (-)-indolactam V, which has the fundamental structure of teleocidins, by rat liver microsomes. AB - Metabolic activation and/or deactivation of indole alkaloid tumor promoter, (-) indolactam V (ILV), was examined using rat liver microsomes. Reaction of ILV with the microsomes supplemented with NADPH and MgCl2 gave three major metabolites, which were identified as (-)-N13-desmethylindolactam V and two diastereomers of ( )-2-oxyindolactam V at C-3. The tumor-promoting activities of these metabolites were evaluated by induction of Epstein-Barr virus early antigen and inhibition of specific binding of [3H]-12-O-tetradecanoylphorbol-13-acetate to a mouse epidermal particulate fraction, and proved to be conspicuously lower than that of ILV. These results demonstrate that the metabolism of ILV results in detoxification, and that it itself is the tumor-promoting entity. Studies on the enzymes concerned with this metabolism suggested the involvement of cytochrome P 450-containing mixed-function oxidases. Similar deactivation seems to be possible by skin, where the mixed-function oxidases are known to exist. PMID- 3109759 TI - Inhibition of eicosanoid production by BW755C does not attenuate sepsis-induced alterations in glucose kinetics. AB - Previous studies have indicated that various arachidonic acid metabolites are involved in the cardiovascular dysfunction seen during endotoxemia and sepsis. However, the possible role of these metabolites in mediating the metabolic alterations under similar conditions remains to be elucidated. Thus, the purpose of the present study was to determine if cyclooxygenase and lipoxygenase blockade could prevent the elevated rates of glucose appearance (Ra), glucose recycling, and hyperlactacidemia seen during hypermetabolic sepsis. Sepsis was induced in chronically catheterized conscious rats by multiple injections of live Escherichia coli via a subcutaneous catheter. Septic animals received intravenous (i.v.) injections of BW755C every 6-8 h to block both the cyclooxygenase and lipoxygenase pathways. Glucose kinetics were assessed in 24-h fasted rats by using a constant i.v. infusion of [6-3H] and [U-14C]-glucose. Treatment with BW755C prevented the 1-2 degrees C increase in body temperature induced by sepsis in the vehicle-treated animals. Septic rats receiving saline instead of BW755C exhibited an elevated plasma lactate concentration and increased rates of glucose appearance, recycling, and metabolic clearance. The sepsis-induced alterations in these variables were not attenuated by BW755C. These results suggest that neither arachidonic acid metabolites nor elevated body temperature are responsible for increasing glucose production and utilization in hypermetabolic septic rats. PMID- 3109760 TI - Venous and arterial endothelia: different dilator abilities in dog vessels. AB - It has been demonstrated by other investigators that endothelium-dependent vasodilators are more effective on arterial tissue than on venous tissue. The purpose of this study was to determine if this was due to a difference in the sensitivity of arterial and venous smooth muscle to the endothelial dilator (EDRF) or to a difference in the ability of arterial and venous endothelia to release EDRF. To differentiate between these two possibilities, an in vitro "sandwich" preparation was used in which the mechanical response to endothelium dependent dilators of a de-endothelialized vessel was determined when "sandwiched" with an endothelialized vessel. Using dog femoral artery and saphenous vein, it was determined that acetylcholine (ACh), the ionophore A23187, and thrombin were endothelium-dependent dilators of the femoral artery, but their dilatory ability was significantly less in the saphenous vein. However, if the de endothelialized saphenous vein was "sandwiched" with an endothelialized femoral artery, both ACh and A23187 significantly relaxed the vein. No relaxation of the de-endothelialized femoral artery occurred when it was "sandwiched" with an intact saphenous vein. Sodium nitroprusside, thought to act by a mechanism similar to EDRF, relaxed equally the saphenous vein and femoral artery. These observations suggest that the difference in responsiveness between femoral arteries and saphenous veins to endothelium-dependent dilators is due more to differences in the ability of their endothelia to release EDRF than to an inability of their smooth muscle to respond to EDRF. PMID- 3109761 TI - Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart. AB - Changes in cytosolic free calcium concentration during myocardial ischemia were measured by 19F NMR in 5FBAPTA-loaded perfused rat hearts. The hearts were perfused with Krebs-Henseleit buffer containing 5 microM of the acetoxymethyl ester of 5FBAPTA, which was hydrolyzed by cytosolic esterases to achieve cytosolic concentrations of 5FBAPTA of 0.12 to 0.65 mM. Cytosolic free calcium concentrations were calculated as the product of the ratio of peak areas for bound and free 5FBAPTA in the NMR spectra and the dissociation constant (708 nM). The basal cytosolic calcium concentration, measured in potassium or magnesium arrested hearts, was 252 nM, and the time-average calcium concentration in beating hearts was 630 nM. Following the onset of total ischemia, there was no immediate substantial change in cytosolic calcium despite a rapid decline in creatine phosphate and ATP and a marked increase in inorganic phosphate as monitored by 31P NMR, but by 10 minutes, there was a substantial increase in free calcium concentration. The ratio of peak areas of bound and free 5FBAPTA returned to the preischemic value during reperfusion, and there was no detectable loss of 5FBAPTA from the heart. Creatine phosphate was also restored to its preischemic level during reperfusion. These results indicate that cytosolic free calcium increases during ischemia and is not immediately associated with lethal injury. This increase in cytosolic calcium may activate degradative enzymes that eventually could compromise myocyte viability. PMID- 3109762 TI - Fluid reabsorption and glucose consumption in edematous rat lungs. AB - Solute and water uptake were studied in isolated perfused rat lungs with airspaces filled with the perfusion fluid. The albumin in this solution was labelled with Evans blue (T-1824), and uptake of fluid from the airspaces was documented by an increase in T-1824 concentration in airway fluid of 6.5 +/- 1.6% (n = 5, SEM) at 1 hour and 12.2 +/- 0.9% (n = 10) at 2 hours. The only detectable osmotic force that could have contributed to a loss of fluid from the alveolar fluid was a decrease in airspace glucose concentrations, which fell much more rapidly (from 150 mg/dl to 58.7 +/- 7.1 mg/dl, n = 10, after 2 hours) than plasma glucose (from 150 mg/dl to 128.9 +/- 3.7 mg/dl). Addition of 5 X 10(-5) M terbutaline to the perfusate and airspace solutions nearly doubled fluid reabsorption at 1 hour, an effect that was inhibited by propranolol and did not appear to be related to glucose consumption. Exposure to terbutaline for 2 hours increased epithelial permeability to 3H-mannitol and 22Na+. These observations suggest that active sodium transport and epithelial metabolism or transport of glucose in airway fluid may each play a role in the reabsorption of edema fluid. PMID- 3109764 TI - Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. AB - Intravenous administration of 80 mg of recombinant tissue plasminogen activator (rt-PA, 40, 20, and 20 mg in successive hours) and streptokinase (SK, 1.5 million units over 1 hr) was compared in a double-blind, randomized trial in 290 patients with evolving acute myocardial infarction. These patients entered the trial within 7 hr of the onset of symptoms and underwent baseline coronary arteriography before thrombolytic therapy was instituted. Ninety minutes after the start of thrombolytic therapy, occluded infarct-related arteries had opened in 62% of 113 patients in the rt-PA and 31% of 119 patients in the SK group (p less than .001). Twice as many occluded infarct-related arteries opened after rt PA compared with SK at the time of each of seven angiograms obtained during the first 90 min after commencing thrombolytic therapy. Regardless of the time from onset of symptoms to treatment, more arteries were opened after rt-PA than SK. The reduction in circulating fibrinogen and plasminogen and the increase in circulating fibrin split products at 3 and 24 hr were significantly less in patients treated with rt-PA than in those treated with SK (p less than .001). The occurrence of bleeding events, administration of blood transfusions, and reocclusion of the infarct-related artery was comparable in the two groups. Thus, in patients with acute myocardial infarction, rt-PA elicited reperfusion in twice as many occluded infarct-related arteries as compared with SK at each of seven serial observations during the first 90 min after onset of treatment. PMID- 3109763 TI - Evidence that bradykinin stimulates renal prostaglandin synthesis by a mechanism distinct from that of other vasoactive substances. AB - Arginine-vasopressin (AVP), angiotensin II (AII), and norepinephrine (NE) are known to stimulate prostaglandin (PG) synthesis in the intact rat kidney perfused with Tyrode's solution by a mechanism that requires intracellular Ca2+, while PG synthesis elicited by bradykinin (BK) is independent of Ca2+. To elucidate further the differences in the mechanism of action of BK and other vasoactive agents, in this preparation we have investigated the effect of caffeine, an agent known to interfere with the uptake and storage of Ca2+ in intracellular sites, on renal output of PGE2 and 6-keto-PGF1 alpha elicited by AVP, AII, NE, and BK; various combinations of the maximal doses of BK, AII, AVP, and NE on renal PG synthesis; and RHC 80267, an inhibitor of diglyceride and monoglyceride lipase, on the output of PGs produced by these vasoactive agents. Infusion of 1 mM caffeine inhibited PG output elicited by AVP, AII, and NE but not that caused by BK in the absence of extracellular Ca2+. Combined administration of maximal doses of BK (2.8 nmol) with that of AII (0.28 nmol), AVP (0.27 nmol), or NE (3.2 nmol) but not AVP and AII, NE and AVP, or NE and AII produced an additive effect on renal PG output in the presence or absence of Ca2+. The renal vasoconstrictor effect of AVP, AII, and NE produced in the presence of Ca2+ was not additive and remained unaltered when given together with BK.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109765 TI - Afferent fiber innervation on acupuncture points and its role in acupuncture analgesia. PMID- 3109766 TI - [The effect of intracortical stimulation of the somatic sensory area mesencephalon reticular formation and its relation to the acupuncture effect]. PMID- 3109767 TI - [Influence of acupuncture on the leu-enkephalia content of the brain and spinal cord of rats]. PMID- 3109768 TI - [Effect of acupuncture on the ultrastructure of the liver in rats]. PMID- 3109769 TI - [Role of the n. dorsal raphe and cyproheptadine on the changes of unit discharges in the dorsal hippocampal pyramidal layer under electroacupuncture in rats]. PMID- 3109770 TI - [Effects of electroacupuncture stimulation (EAS) of different frequencies on the excitability of fibers of various groups]. PMID- 3109771 TI - [A study of the specificity of the depressing action of the "zusanli" acupoint in visceral pain of conscious cats]. PMID- 3109772 TI - [Morphological study on the low impedance line along channels]. PMID- 3109773 TI - [Clinical application of the lines of latent propagating sensation and low impedance along channels in the treatment of emphysema]. PMID- 3109774 TI - Liquid-chromatographic determination of tocainide in plasma, with N-acyl derivatives of tocainide as internal standards. PMID- 3109775 TI - Absence of statistical association between hyperglycemia and metabolic acidosis in both type I and type II diabetic patients on chronic dialysis. PMID- 3109776 TI - Immunoglobulin A (lambda chains) conjugated with lactate dehydrogenase in serum. AB - An atypical pattern for lactate dehydrogenase (EC 1.1.1.27) isoenzymes in a patient with sclerosis of the bladder neck was ascribable to complexing between lactate dehydrogenase and IgA. This complex formation was also replicable "in vitro." We determined that the IgA bound to lactate dehydrogenase was of the lambda type, a very unusual occurrence. PMID- 3109777 TI - Effect of tetrasodium EDTA on enzymatic determinations of urinary oxalate. AB - We studied the effects of pretreating urine samples with tetrasodium EDTA (TEDTA) before measuring urinary oxalate with an enzymatic kit (Sigma). Mean analytical recovery of added oxalic acid was only 49% (SD +/- 13%) when the assay was performed as recommended by the manufacturer, but treating samples with TEDTA improved recoveries (96 +/- 10%). In 20 unselected 24-h urine samples assayed with and without TEDTA treatment, the mean oxalate concentrations were significantly (P less than 0.001) different: 15.6 +/- 8.7 and 12.2 +/- 7.9 mg/L, respectively. TEDTA-treated urine samples stored for 14 days at -20 degrees C lost 20% of their oxalate concentration. Use of TEDTA simplifies sample preparation by eliminating the alkalinizing step needed to dissolve EDTA or disodium EDTA. PMID- 3109778 TI - Stability of free apolipoprotein A-1 concentration in serum, and its measurement in normal and hyperlipidemic subjects. AB - Free apolipoprotein A-1 (free A-1) is a low-molecular-mass complex of protein and lipid containing apolipoprotein A-1 (apo A-1). Using crossed immunoelectrophoresis, we separated free A-1 from the apo A-1 in high-density lipoproteins (HDL) and quantified free A-1 by comparison with a reference serum (containing 1.45 g of apo A-1 per liter) diluted in 9 mol/L urea solution. This latter treatment yields apo A-1 containing protein-lipid complexes of the same size and electrophoretic mobility as free A-1. Within-day precision (CV), determined by replicate analysis of two samples with mean free A-1 concentrations of 48 and 138 mg/L, was 9.1 and 7.2%, respectively. We also showed that the concentration of free A-1 is not stable in serum or plasma either at 4 degrees C or when frozen. The mean concentration of free A-1 in 28 fasted, healthy subjects was 75.3 (SD 13.6) mg/L. The postprandial increase was not statistically significant. The percentage of total apo A-1 in the free form in serum ranged from 3.5% to 8.1%, less than the 10% to 30% reported by others who used radial immunodiffusion to measure free A-1. Because radial immunodiffusion does not separate free A-1 from HDL, we believe that that technique overestimates free A 1. We also used crossed immunoelectrophoresis to measure free A-1 in 76 hyperlipidemic patients. Those with Fredrickson types III and V had significantly increased concentrations of free A-1 (P less than .0001). Correlations between free A-1 and cholesterol and triglycerides in serum were significant (P less than .005 and P less than .001, respectively). Possible roles for free A-1 in lipid metabolism are discussed. PMID- 3109779 TI - A calibrated fluorescence polarization assay for assessment of fetal lung maturity. AB - The mechanism of a new fluorescence polarization method for measuring phospholipid in amniotic fluid is described. The fluorescence polarization of a surfactant fluorescent dye solubilized in amniotic fluid correlates significantly with the L/S ratio. Model studies indicate that this results primarily from partitioning of the dye between endogenous albumin, which causes a high fluorescence polarization, and dispersed phospholipid, which causes a much lower polarization. The fluorescence polarization can be compared with a calibration curve to give the ratio of phospholipid to albumin in the sample. This procedure may prove useful in antenatal assessment of fetal lung maturity. PMID- 3109780 TI - Decrease of free thyroxin in serum of lactating women. AB - We measured thyroid hormones and thyroxin-binding proteins in serum from 62 normal lactating and 52 nonlactating women at three months postpartum, and compared these values with those for 42 nonpregnant control women of similar age. Mean thyroxin concentrations in the lactating and nonlactating women were significantly (P less than 0.001) lower than that of the nonpregnant controls, but there was no significant difference (P greater than 0.2) in triiodothyronine concentration among these three groups. Free T4 concentration was significantly (P less than 0.01) lower in lactating women than in controls. The reverse-T3 concentrations in both lactating and nonlactating women were significantly (P less than 0.001) lower than in controls, and were significantly (P less than 0.001) lower in lactating than in nonlactating women. The concentration of thyroxin-binding globulin was significantly higher in lactating women than in controls, and the albumin concentration was significantly lower in women postpartum than in controls. Evidently, regulation of thyroid hormone in women postpartum, especially during lactation, differs from that in nonpregnant women. PMID- 3109781 TI - Immunoenzymatic quantification of low concentrations of thyrotropin. AB - We evaluated an immunoenzymatic assay (Abbott HTSH EIA) for thyrotropin (TSH) as a tool for detecting hyperthyroidism and for monitoring thyroid hormone suppressive therapy in patients with nodular goiter, thyroid carcinoma, and hypopituitarism. We also tested with thyroliberin (TRH), to determine the correlation between peak and basal TSH in suppressed patients. For comparison, we used a nonequilibrium radioimmunoassay optimized for maximum sensitivity (J Clin Endocrinol Metab 1975;41:676). Hyperthyroid patients with values for either or both triiodothyronine and thyroxin above the normal reference interval had Abbott assay values less than or equal to 0.2 milli-int. unit/L, clearly below the Abbott assay normal range, as determined in 116 euthyroid subjects. We detected one-third of the suppressed patients (greater than or equal to 0.3 milli-int. unit/L) with RIA, 69% with the Abbott assay (TSH greater than or equal to 0.04 milli-int. unit/L). Only 20% of patients with undetectable basal TSH values in the Abbott assay responded to TRH with a detectable peak TSH value; the peak TSH value after TRH was proportional to the basal TSH value. A single basal TSH measurement by the Abbott HTSH EIA should be adequate for monitoring the degree of thyroidal suppression in thyroid-hormone-treated patients. PMID- 3109782 TI - Serum haptoglobin concentrations in concurrent hemolysis and acute-phase reaction. PMID- 3109783 TI - Measurement of apolipoprotein A-I in serum with the Technicon RA-1000 system. PMID- 3109784 TI - Immunoturbidimetry of apolipoprotein A-II in a centrifugal analyzer. PMID- 3109785 TI - Multiple myeloma with serum IgG kappa and Bence Jones lambda biclonal gammopathy. PMID- 3109786 TI - An evaluation of four methods for the detection of heterozygous cystinuria. AB - Heterozygotes for cystinuria (types II and III) may be detected on the basis of slight to moderate elevations in urinary cystine, lysine and sometimes arginine. This seems to be a common genetic trait, and there are indications of an increased risk of urinary stone disease. In order to test the sensitivity and reliability of the procedures normally used for screening and diagnosis of heterozygous cystinuria, we studied 32 heterozygotes previously diagnosed by ion exchange chromatography of urinary amino acids, and 23 healthy individuals. A random urine sample from each subject was analysed using the cyanide nitroprusside test, thin-layer amino acid chromatography, colorimetric estimations of cystine and lysine, and ion-exchange amino acid chromatography. Thin-layer chromatography provided the highest sensitivity. Thus the frequency of heterozygotes calculated in previous studies, based on screening by the cyanide nitroprusside test, may be under-estimated. The colorimetric estimations of cystine and lysine provided low sensitivity as screening tests and, compared with the ion-exchange chromatography, were unreliable diagnostic methods. PMID- 3109787 TI - Purification of placental protein PP12 from human amniotic fluid and its comparison with PP12 from placenta by immunological, physicochemical and somatomedin-binding properties. AB - Human amniotic fluid was found to contain a protein which is immunochemically indistinguishable from placental protein PP12. This protein was purified by gel filtration, hydrophobic interaction high performance liquid chromatography and anion-exchange chromatography. The relative molecular mass as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis was 34,000, and the isoelectric point was 4.9. Tryptic peptides of amniotic fluid PP12 as determined by reversed phase high performance liquid chromatography were similar to those of placental PP12. Both had the N-terminal amino acid sequence Ala-Pro-Trp-Gln-, which is the same as previously reported for a somatomedin-binding protein. Both placental PP12 and amniotic fluid PP12 were found to bind somatomedin C (IGF-I) with high affinity, Ka = 1 X 10(9) l/mol). Amniotic fluid is an ideal source of this somatomedin-binding protein, and the purification method described allows rapid isolation of PP12 under mild conditions which are essential for studies on its biological function. PMID- 3109788 TI - Status epilepticus within the Lennox-Gastaut syndrome: clinical characteristics and management. AB - This report describes 2 cases, 7 and 8 years of age, with the Lennox-Gastaut Syndrome and status epilepticus. Both cases responded favorably, clinically and in their EEGs, to continuous therapeutic control with clonazepam, and remained under control with valproic acid. PMID- 3109789 TI - Contribution to the 18q- syndrome. A patient with del(18) (q22.3qter). AB - A patient with the typical features of the 18q- syndrome, but with the deletion restricted to the most distal part, bands q22.3----qter is reported. The cytogenetic finding is supported by a decrease in activity of the enzyme peptidase A. PMID- 3109790 TI - Albinism, or the NOACH syndrome (the book of Enoch c.v. 1-20). AB - After a 4-year multidisciplinary study of albinism our findings will be presented here. Over a hundred albinos were examined, together with their heterozygote family members. Given this substantial patient and subject sample we were provided with the opportunity to: evaluate the results of standard diagnostic procedures, for example pedigree analysis, ocular and clinical examination; determine the diagnostic value of biochemical, and ultrastructural tests; and develop a new and viable albino diagnostic protocol, particularly for electrophysiological examination. In the conclusions the following subjects are in order: DIAGNOSIS: Our most important finding up till now is that normally pigmented people who do not look like albinos can in fact be albinos. DIFFERENTIAL DIAGNOSIS: It appears that patients with autosomal recessive albinism can be normally pigmented, and patients with X-linked albinism can be severely hypopigmented. We therefore propose to abandon the terms oculo-cutaneous albinism (OCA), and X-linked ocular albinism (XOA), and use the terms autosomal recessive albinism, and X-linked albinism instead. X-linked albinism Forsius Eriksson type (XOAF): We assume that XOAF does not represent a true form of albinism. CLASSIFICATION: Our results indicate that the phenotypical albino classification, which was a base for Witkop et al. (1978) to also obtain a genetical classification, supported by the hairbulb test, has not proved to be useful for the classification of tyrosinase negative (TNOCA), tyrosinase positive oculocutaneous albinism (TPOCA), and autosomal recessive ocular albinism (AROA) as genetically distinct forms. Prevalence: Our prevalence estimate for all forms of albinism is at least 1:15,000, about 10% of the albinos have X-linked albinism. DEFINITION: We want to modify the albino definition as a hereditary and congenital inborn error of metabolism related to the pigment cell, and resulting in a systemic disorder that is characterized by anomalies of eyes, and hypopigmentation in most cases or absence of pigment in skin, hair, and eyes, and of which the neuro-anatomical consequences are the most characteristic. PMID- 3109791 TI - The role of prostaglandins in C3a-mediated suppression of human in vitro polyclonal antibody responses. AB - Suppression of polyclonal antibody responses in human peripheral blood mononuclear cell cultures by human C3a appears to involve the release of endogenous prostaglandins from monocytes. C3a was found, under the experimental conditions employed, to activate the cyclooxygenase pathway of arachidonic acid metabolism with the release of large amounts of the prostaglandin E2 species. Suppression of the protein A-induced polyclonal antibody response by C3a is abrogated by the prostaglandin synthesis inhibitor indomethacin. In addition, physiologic amounts of exogenous PGE2 were able to inhibit polyclonal antibody secretion in a manner similar to the suppression observed when C3a was added to culture. These results suggest that C3a-induced release of prostaglandins could be a major element in immunosuppression induced by C3a. PMID- 3109792 TI - Humoral immune response in patients with hemophilia. AB - Hemophiliacs require frequent infusions of allogeneic proteins to control bleeding. Previous reports have demonstrated that thymus-derived lymphocytes (T cells) from hemophiliacs are antigenically primed to the lyophilized antihemophilic factor and that natural killer cells from hemophiliacs demonstrate impaired response to interferon-beta and -gamma Some aspects of the humoral immune response were investigated in eight patients who require large amounts of Factor VIII. Polyclonal hypergammaglobulinemia was detected in six patients and seven had elevated titers of autoantibodies of various specificities. There was no evidence of impaired concanavalin A-inducible T-suppressor cell activity. Polyclonal immunoglobulin secretion secondary to pokeweed mitogen in vitro was elevated in three of eight patients and depressed in five. Spontaneous production of both B-cell growth and differentiation factors (BCGF and BCDF) was elevated but mitogen-induced production was impaired. These data demonstrate that the humoral immune response of hemophiliacs may be chronically stimulated, thus impairing their ability to respond to new antigens such as viruses. PMID- 3109793 TI - Renal histological lesions and clinical syndromes in multiple myeloma. Renal Immunopathology Group. AB - This retrospective multicenter study, based on 42 patients affected by renal damage due to multiple myeloma, analyzes the renal biopsy results, the clinical data at the time of biopsy and the subsequent renal outcome in order to clarify the correlations existing between clinical and histological changes. Plasmocytoma components were Bence Jones alone in 55% of the patients and light-chain excretion was present in over 90%. Rapidly progressive renal failure was the most frequent clinical presentation (27 cases). The histological lesions directly attributable to multiple myeloma were subdivided into 3 basic categories: related to light-chains, direct tumor involvement of renal parenchyma and attributable to systemic effects of neoplastic disease. Light-chains seemed to cause renal lesions in 59.4% of the cases. Myeloma cast nephropathy was the prominent bioptic diagnosis established (20 cases). Among the clinical, laboratory and histological parameters studied, only the degree of tubular-interstitial damage was significantly correlated to the renal outcome in the 32 patients who had an adequately documented follow-up period. PMID- 3109794 TI - The influence of anti-parasitic therapy on the course of the glomerulopathy associated with Schistosomiasis mansoni. AB - Although several aspects of the association between S. mansoni infection and renal disease are well known, the influence of the anti-parasitic therapy on the clinical course of the glomerulopathy remains undefined. With the aim of studying this aspect, 16 patients with glomerulopathy associated with schistosomiasis mansoni were evaluated (proteinuria and levels of BUN and creatinine) before therapy, 1 week, 1 month, 2-3 months and 6 months after therapy of the parasitic infections. During the follow-up of such cases no benefit could unquestionably be demonstrated in the patients. Also, no permanent deterioration of renal function related to anti-parasitic therapy could be documented. It is concluded that the treatment of the S. mansoni infection, once the consequent glomerulopathy is clinically apparent, does not influence the clinical course of the disease. PMID- 3109795 TI - Intravenous flecainide acetate for the clinical management of paroxysmal tachycardias. AB - Intravenous flecainide acetate (2 mg/kg) was administered to 40 patients undergoing routine electrophysiological evaluation for the investigation of recurrent paroxysmal tachycardias. Ten patients had recurrent atrial flutter, 11 patients had recurrent atrial fibrillation, one of whom also had paroxysmal left atrial tachycardia, and 19 patients had recurrent ventricular tachyarrhythmias (17 with recurrent ventricular tachycardia and 2 with recurrent fascicular tachycardia). Flecainide was administered during tachycardia (over 5 to 10 minutes) to all patients with atrial flutter, to 10 patients with atrial fibrillation, and to 17 patients with ventricular tachyarrhythmias. In the remaining 3 patients with ill-sustained arrhythmias flecainide was administered during sinus rhythm and reinitiation of tachycardia was then attempted. Flecainide restored sinus rhythm in only 2 patients with atrial flutter (20%), in 9 patients with atrial fibrillation (90%), in 12 patients with ventricular tachycardia (80%), and in one of the 2 patients with fasicular tachycardia. Flecainide also successfully terminated the left atrial tachycardia. Two patients experienced proarrhythmic side effects during flecainide administration, one of whom required intervention by cardioversion. Minor dose effects included oral paresthesia, transient drowsiness or dizziness, and occasional visual blurring. Flecainide acetate is an effective antiarrhythmic agent for the acute termination of recent onset paroxysmal atrial and ventricular tachyarrhythmias. PMID- 3109796 TI - Endocardial fibroelastosis in mucopolysaccharidosis type VI. AB - This case report describes two siblings less than 1 year of age who presented severely ill with a dilated cardiomyopathy. Full blood examination in both cases revealed marked granularity of neutrophils suggestive of mucopolysaccharidosis type VI. There were no physical features of a mucopolysaccharidosis but biochemical evaluation confirmed mucopolysaccharidosis type VI in both children. Autopsy in one patient confirmed endocardial fibroelastosis and electron microscopy of fibroblasts in the myocardium showed distention with membrane-bound vacuoles, consistent with a mucopolysaccharidosis. These siblings developed endocardial fibroelastosis before other clinical manifestations of the mucopolysaccharidosis. Assessment for metabolic causes of a cardiomyopathy is important, as cardiac disease may be the initial manifestation of a metabolic disease. PMID- 3109797 TI - Clinical subsets of scleroderma: relevance of fluorescent and precipitating antinuclear antibodies. AB - Sera from 7 patients with localized and 35 with systemic scleroderma were studied for the presence of fluorescent antinuclear antibodies (FANA) (by indirect immunofluorescence on HEp-2 cells) and antibodies to extractable nuclear antigens (anti-ENA) (by immunodiffusion - ID - and counterimmunoelectrophoresis - CIE). In localized disease, antinuclear autoimmunity was limited to 1 FANA positive serum (14%); in systemic disease, the prevalence of FANA was 94% and that of anti-ENA ranged from 29% to 49% (by ID and CIE, respectively). The commonest ENA system, Scl-70, could be easily detected by CIE, in spite of the reported basic nature of the antigen. The anticentromere antibody occurred only in patients with acrosclerosis (7/26-27%), whereas the association of nucleolar + homogeneous FANA, as well as the anti-Scl-70, were found more frequently in diffuse scleroderma (9/9-100% and 6/9-67%, respectively). The presence of the anticentromere antibody excluded that of any anti-ENA, while a close association was found between nucleolar + homogeneous FANA and the anti-Scl-70. Pulmonary involvement was significantly more frequent in nucleolar + homogeneous FANA positive patients; moreover, in two cases the same pattern proved to predict the development of diffuse scleroderma. PMID- 3109798 TI - The in vivo effect of triethylphosphine gold (auranofin), sodium aurothiomalate and azathioprine on natural killer cell activity of patients with rheumatoid arthritis. AB - Natural Killer (NK) cell activity was measured in 80 patients with rheumatoid arthritis (RA) grouped according to medication into 1) controls not in remission inducing therapy, 2) patients treated with oral gold (auranofin), 3) parenteral gold (sodium aurothiomalate) and 4) azathioprine. Baseline, interferon (IF) enhanced and interleukin 2 (Il-2)-enhanced NK cell activity of patients in the two gold groups did not differ from that of controls, while NK cell activity before and after exposure to IF and Il-2 was significantly suppressed in patients on azathioprine (p less than 0.01). The percentage of Large Granular Lymphocytes did not differ in the four groups while the percentage of Leu 11 positive cells and the total number of lymphocytes were significantly lower in the azathioprine group. Sixty out of 80 patients received nonsteroidal anti-inflammatory drugs (NSAID), whereas 20 did not. A comparison of these two groups showed no influence of NSAID on NK cell activity. PMID- 3109799 TI - Complex fractures of the ankle and hindfoot. PMID- 3109800 TI - Congenital oral tumor associated with neurofibromatosis detected by prenatal ultrasound. PMID- 3109801 TI - Myocardial ischemia complicating therapy of status asthmaticus. PMID- 3109802 TI - Leptomonas samueli glycoconjugates. Comparison with Herpetomonas samuelpessoai. AB - Xylose and mannose are the main manosaccharide components of Herpetomonas samuelpessoai and Leptomonas samueli promastigotes. Variations in the xylose/mannose ratios are related to the age of cultures. Phenol-aqueous extraction disclosed in both species the presence of carbohydrate-containing fractions which were both soluble and insoluble in chloroform/methanol/water (10:10.3). The xylose enriched, uronic acid-containing glycoconjugates of L. samueli were mainly composed of (1----4)-linked xylose units (Methylation-mass spectrometry and 13C NMR), similar to the glucuronoxylan of H. samuelpessoai (Mendonca-Previato et al., 1979 Biochem 18 149-154). SDS-PAGE and sugar composition analysis disclosed similarities between glycoconjugates of H. samuelpessoai and L. samueli, two species dwelling in the same host, therefore an example of convergent adaptation. PMID- 3109803 TI - The interaction between sex hormone binding globulin and levonorgestrel released from Norplant, an implantable contraceptive. AB - Two-hundred-and-eighty Indonesian women were provided with Norplant, a levonorgestrel-releasing implant. At various time intervals, up to 5 years after Norplant insertion, levonorgestrel and sex hormone binding globulin (SHBG) were assayed in blood plasma. After an initial burst of approximately 7 nmol/l, the levels of levonorgestrel rapidly decreased during the first month. The decrease continued to a nadir (1.1 nmol/l) which was reached 10 months later. The decrease was followed by an increase to a broad peak of 1.5 nmol/l which was reached 2 years after insertion. Thereafter, a slow-decrease at a rate of approximately 18 pmol/month was seen. SHBG levels decreased significantly already 1 week after insertion. A nadir of levels (25 nmol/l) was reached 3 months later. The levels increased slowly again and remained constant (32 nmol/l) from about 15 months to 5 years. During the entire period of study highly significant correlations of levonorgestrel with SHBG were seen. In another group of 25 women the levels of levonorgestrel and SHBG were studied before and one week after insertion of Norplant. A significant correlation (r = 0.77) was found between the preinsertion levels of SHBG and postinsertion levels of levonorgestrel. PMID- 3109804 TI - Subjective perception of bleeding and serum ferritin concentration in long-term users of Norplant. AB - Serum ferritin was measured in 4 groups of long-term users of NORPLANT implants. The users were divided according to their own subjective perception of bleeding: a random sample of 46 one year active users; 30 active users who had increased bleeding; 39 women who had increased bleeding and had the implants removed; 28 active or terminated users who had reduced bleeding. These four groups were compared with a control group of 68 new acceptors of any method at the same clinic who met the criteria for use of NORPLANT. The mean age, parity, years of schooling and family income were similar for the 5 groups. Mean hematocrit for all NORPLANT groups were significantly higher than the control group. About half of the NORPLANT subjects and controls with normal hematocrit had ferritin levels below 11 ng/ml. The proportion of subjects with ferritin less than 11.0 ng/ml were: Group 1) 48%; 2) 63%; 3) 77%; 4) 36% and CONTROLS: 57%. Mean iron stores for all NORPLANT users did not differ significantly from those of a demographically similar control group. Significant differences were, however, observed in two subgroups of NORPLANT users. Those women who had increased bleeding and requested implant removal had lower mean ferritin levels and those who perceived decreased bleeding as a result of NORPLANT use had higher ferritin concentration. PMID- 3109805 TI - Use of nitroglycerin in the treatment of acute heart failure and cardiogenic shock in patients with myocardial infarction. AB - The effectiveness of nitroglycerin in the treatment of acute heart failure was investigated in 100 patients with myocardial infarction. It was found that nitroglycerin has marked advantages in comparison with cardiac glycosides both as regards its effectiveness and as regards the character of its action on the haemodynamics and the state of the periinfarction zone. In most patients (78%), a favourable effect was attained with intravenous nitroglycerin administration and with additional intake in the form of tablets. Clinical improvement was preceded by normalization of pulmonary artery pressure. Uninterrupted nitroglycerin administration was terminated after normalization and stabilization of haemodynamics. The results showed that with monitoring haemodynamics nitroglycerin can be administered also in haemodynamic disorders, which occur in the early period of cardiogenic shock. PMID- 3109806 TI - Effects of blood volume and discontinuance of ventilation on pulmonary vascular pressures and blood gases in patients with low levels of positive end-expiratory pressure. AB - Hypervolemic, normovolemic and hypovolemic patients with PEEP values less than 10 cm H2O were studied during brief discontinuance of mechanical ventilation to determine whether blood volume status would affect on-off ventilator pulmonary artery pressure (PAP) readings. There were no appreciable hemodynamic effects in patients with blood volume deficits less than one liter. Discontinuance for 1 min decreased PaO2 from 121 +/- 8 (SD) to 77 +/- 7 torr (p less than .001) and increased PaCO2 from 32 +/- 1 to 35 +/- 1 torr (p less than .01). The decreased PaO2 persisted up to one hour after return to mechanical ventilation. Our data reveal that brief discontinuance of ventilation in the normovolemic or hypervolemic patient with physiologic levels of PEEP does not increase the accuracy of PAP measurements. However, with severe hypovolemia, marked reductions in PAP may occur with discontinuance of mechanical ventilation. The practice of recording PAP off the ventilator and frequent suctioning of patients should be abandoned when interruption of mechanical ventilation has little utility and can result in persistent hypoxemia. PMID- 3109807 TI - Comparison of high-frequency chest wall compression with conventional mechanical ventilation in cats. AB - Six anesthetized paralyzed cats with normal lungs were ventilated by high frequency chest wall compression (HFCWC) at 5 Hz using a single-chamber circumferential cuff enclosing the thorax from the axillae to the xiphisternum. PaCO2 during HFCWC + PEEP (3 cm H2O) was significantly (p less than .0005) lower compared with conventional mechanical ventilation (CMV). End-expiratory lung volume (VL) during HFCWC + PEEP was significantly (p less than .001) lower than VL during CMV + PEEP but was higher than VL during CMV without PEEP. After the cats' lungs were stiffened by repeated saline lavage, CMV + PEEP at a mean airway pressure (Paw) of 10 cm H2O was compared with HFCWC + continuous positive airway pressure (CPAP) at an equal or lower Paw. A significant decrease in PaCO2 (p less than .02) during HFCWC occurred but no significant differences were observed in PaO2, VL, or compliance. Arterial BP and cardiac output were similar between CMV + PEEP and HFCWC + CPAP. In cats with normal lungs, VL can be maintained by applying CPAP during HFCWC, and in those with injured lungs, HFCWC + CPAP produces comparable gas exchange at a Paw equal to or lower than that used during CMV + PEEP. PMID- 3109808 TI - Continuous arteriovenous hemofiltration in critically ill children with acute renal failure. AB - Last year, five critically ill children with acute renal failure were treated by continuous arteriovenous hemofiltration. Mean treatment duration was 326 +/- 89 (SD)h, for a total of 1632 h. Mean ultrafiltration rates of 5.4 +/- 1.7 ml/min X m2 achieved mean serum urea levels of 150 +/- 25 mg/dl and a decline of mean prehemofiltration serum creatinine level of 3.5 +/- 3.6 to 2.9 +/- 2.0 mg/dl posthemofiltration. Continuous arteriovenous hemofiltration allowed adequate parenteral nutrition with a mean caloric intake of 79.6 +/- 9.2 kcal/kg X day. In the four surviving patients, urinary output started between 12 and 42 days after the onset of acute renal failure. Continuous arteriovenous hemofiltration is a very effective extracorporeal therapeutic system to control azotemia, fluid, and electrolyte balance in critically ill children with acute renal failure and hemodynamic instability. PMID- 3109809 TI - Late-phase reaction and tear fluid cytology in the rat ocular anaphylaxis. AB - Tear fluid cytology is described for the early and late phases of ocular anaphylaxis in actively immunized Sprague-Dawley rats. Tears were collected from both eyes of the rats before challenge and at 1, 2, 4, 6, 8, 10, 12, 24, and 48 h after topical challenge with di-DNP-lysine in one eye and PBS in the fellow eye. Results showed a statistically significant increase in the Aggregate Cell Rating, which represents the aggregate scores in neutrophil, eosinophil, lymphocyte, and atypical epithelial cell levels, in antigen-treated vs control eyes. This report is the first to use a cytologic study of tear film to detect the late phase of ocular anaphylaxis in the rat. Cytology of the tear film could be applied to the study of allergic conjunctivitis in both animals and humans. PMID- 3109811 TI - In vitro and in vivo models for monitoring the adoptive immunotherapeutic effects of recombinant gamma-interferon-activated human monocytes. PMID- 3109810 TI - Cholinergic stimulation of phosphatidylinositol hydrolysis by rat corneal epithelium in vitro. AB - Phosphatidic acid (PA) is an obligate intermediate in the phosphatidylinositol (PI) cycle and may serve as a sensitive marker for this pathway of reactions. Previously, we have shown that acetylcholine (ACh) stimulates formation of labeled PA in whole rat corneas whose phospholipids were prelabeled with [14C]arachidonate. To determine which layer of the cornea exhibits the ACh effect, intact epithelium was isolated from the rest of the corneal tissue (designated "stroma/endothelium") by incubating rat corneas with neutral protease and then stripping off the epithelium using forceps. The epithelium was ultrastructurally normal and avidly incorporated [14C]arachidonate into phospholipids; the stroma/endothelium had only trace incorporation. [14C]Arachidonyl-PA formation by the epithelium was significantly increased after a 37 second (+58%) and was maximal after a 5.0 minute (+188%) incubation in the presence of 1 mM ACh. The stimulation by ACh was blocked by atropine and scopolamine but not by d-tubocurarine. The epithelium also incorporated significant quantities of [3H]inositol into phosphatidylinositol (PI), phosphatidylinositol monophosphate (PIP), and phosphatidyl-inositol bisphosphate (PIP 2). When [3H]inositol-labeled epithelia were incubated for 5 minutes with 1 mM ACh, [3H]inositol monophosphate (IP) was increased 200%, [3H]inositol bisphosphate (IP2) was increased 225%, and [3H]inositol 2 trisphosphate (IP3) was increased 74%. These results suggest that muscarinic cholinergic receptors may be an important regulator of the PI cycle in corneal epithelium and thus may affect intracellular calcium mobilization and epithelial proliferation and regeneration. PMID- 3109812 TI - Extraluminal and intraluminal PCO2 levels in the ischemic intestines of rabbits [correction of rats]. PMID- 3109813 TI - Comparison of progressive exercise performance of normal subjects and patients with primary pulmonary hypertension. AB - The extent of exercise limitation and the mechanisms for that limitation in 11 patients with primary pulmonary hypertension (PPH) were studied by progressive, upright cycle ergometry. All patients had a mean pulmonary artery pressure of 30 mm Hg or higher (mean, 56 +/- 15), normal pulmonary function testing, normal pulmonary capillary wedge pressure, and pulmonary angiography consistent with the diagnosis. Rest and exercise data obtained from the patients with PPh were compared with data obtained from 11 matched, sedentary control subjects. Mean maximal oxygen consumption (VO2) was 13 +/- 4 ml/kg/min in the PPH group compared with 28 +/- 7 ml/kg/min in the controls. At maximal VO2 the minute ventilation (VE) was similar; however, the VE at any level of carbon dioxide production (VCO2) during rest and exercise was significantly higher in the PPH group. Maximal heart rate and oxygen pulse (VO2/heart rate) was significantly higher in the control group (148 +/- 18 vs 180 +/- 24, and 6.3 +/- 2.2 vs 9.9 +/- 3.9, respectively). Anaerobic threshold occurred earlier during progressive exercise in the PPH group and correlated positively with the maximal oxygen pulse achieved in patients with PPH. In conclusion, patients with PPH have severe exertional limitation due to cardiovascular factors with an inability to maintain appropriate oxygen delivery to the body during exercise. No respiratory impairment was recognized; however, an exaggerated ventilatory response to exercise at any level of VCO2 was found. PMID- 3109815 TI - Synergy of imipenem--a novel carbapenem, and rifampin and ciprofloxacin against Pseudomonas aeruginosa, Serratia marcescens and Enterobacter species. AB - Although imipenem inhibits most bacteria at very low concentrations, some Pseudomonas aeruginosa, Serratia marcescens and Enterobacter species are resistant or become resistant after exposure. At concentrations of rifampin equivalent to those attainable in man after daily oral ingestion of 600 mg, synergy of imipenem and rifampin was found for 52% of 62 P. aeruginosa and an additive effect for 37%. Against 30 S. marcescens synergy of imipenem and rifampin was not found, but an additive effect was noted for 47% of the isolates. With 32 Enterobacter isolates 35% were synergically inhibited, and an additive effect was found against 38% of the strains. Imipenem and ciprofloxacin were synergistic for 8% of P. aeruginosa and 22% of Enterobacter. Eighty-seven percent of P. aeruginosa isolates with imipenem MIC greater than or equal to 4 micrograms/ml were synergistically inhibited by the combination of imipenem rifampin. Imipenem MIC and MBC were lowered to 1-2 micrograms/ml and to 2-4 micrograms/ml for rifampin. MIC of imipenem and ciprofloxacin were 0.5-2 and 0.05 0.1 micrograms/ml, respectively. When a triple combination of imipenem-rifampin ciprofloxacin was studied, 62% of P. aeruginosa, 32% of Enterobacter spp. and 47% of S. marcescens were synergistically inhibited. PMID- 3109814 TI - Pulmonary vasodilator therapy for chronic obstructive pulmonary disease and cor pulmonale. Treatment with nifedipine, nitroglycerin, and oxygen. AB - The present study was undertaken to evaluate the short-term effects of nitroglycerin, nifedipine, and supplemental oxygen on hemodynamics and gas exchange in 11 patients in stable condition with chronic obstructive pulmonary disease and cor pulmonale. In general, both intravenous nitroglycerin and sublingual nifedipine significantly reduced the pulmonary vascular resistance index. For the group as a whole, nifedipine decreased the pulmonary vascular resistance index by significantly increasing the cardiac index, with minimal reductions in mean pulmonary arterial pressure. Conversely, nitroglycerin decreased the pulmonary vascular resistance index by markedly reducing the mean pulmonary arterial pressure but also decreased the cardiac index in some patients. Nitroglycerin also caused a significant decrease in mixed venous oxygen tension. Administration of oxygen did not cause any clinically significant improvement in resting hemodynamics following short-term administration. During the follow-up period, eight of 11 patients who were treated with pulmonary vasodilators in addition to long-term therapy with low-flow oxygen died within a mean of six months. This rate of survival was not significantly different than an age-matched and sex-matched control group with similar severity of disease who received only long-term therapy with low-flow oxygen. Based on these data, it seems unlikely that a substantial increase in survival will be obtained by combining pulmonary vasodilators with long-term oxygen therapy in patients with stable emphysema who have cor pulmonale and carbon dioxide retention. PMID- 3109816 TI - Combined resistance to quinolones and beta-lactams after in vitro transfer on single drugs. AB - Single and combined resistance to quinolones and beta-lactams was determined after serial transfers of 18 selected strains of Pseudomonas aeruginosa (5), Acinetobacter calcoaceticus (3) and beta-lactamase producing enterobacterial strains (10), in broth dilutions of 4 quinolones and 8 beta-lactams. Two definitions for resistance were used: (I) 8-fold MIC increase and stability of acquired resistance after five transfers in drug-free broth; and (II) 8-fold MIC increase over the breakpoint level. Using definition I, after transfers on a beta lactam, resistance to one or more beta-lactams was noted in 45%, to one or more quinolones in 7% of strains. After transfers on a quinolone, the frequency of resistance to quinolones was 82%, to beta-lactams 26%. When all tests were counted separately, the resistance percentages were lower, but they showed the same trend. Calculation according to definition II showed quinolone resistance in 5.4% of all tests after transfer on a beta-lactam and beta-lactam resistance in 23% after transfer on a quinolone. Serial transfers on imipenem led to fewer cases of resistance (13%) to beta-lactams than transfers on any other beta-lactam (19-39%). There were no conclusive differences between the 7 other beta-lactams. PMID- 3109817 TI - In vitro evaluation of Ro 23-6240, a new fluorinated 4-quinolone. AB - The in vitro antibacterial activity of Ro 23-6240 was assessed and compared with those of ciprofloxacin and beta-lactam antibiotics including several oral compounds against members of the family Enterobacteriaceae (n = 130) and Pseudomonas spp. (n = 31). In general, Ro 23-6240 was 2 dilution steps less active than ciprofloxacin. For the Pseudomonas spp. the MICs for 90% inhibition were 2 and 0.5 mg/1 for Ro 23-6240 and ciprofloxacin, respectively. For the other species tested, the MIC90 values for Ro 23-6240 ranged from 0.031 to 1 mg/1 and for ciprofloxacin from 0.016 to 0.25 mg/1. Spontaneous Ro 23-6240-resistant mutants were only isolated from Enterobacter cloacae with a frequency similar to that of ciprofloxacin (4.8 X 10(-8) and 2.4 X 10(-8), respectively). No resistant mutants were isolated from Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae and Pseudomonas aeruginosa at concentrations of 4 and 8 times the MIC of Ro 23-6240 or ciprofloxacin (frequency less than 10(-9). PMID- 3109818 TI - Light microscopic observations on the proliferation and growth of human echinococcosis. PMID- 3109819 TI - Antimetastatic activity of lymphokine-activated killer cells to rat fibrosarcoma (WBT-2M) and rat mammary carcinoma (SST-2). PMID- 3109822 TI - Pathological changes in red cell series: electron microscopic study on bone marrow cells of some blood disorders. PMID- 3109820 TI - The theory and practice of simple articulator complete denture tooth arrangement. PMID- 3109821 TI - HLA related genetic control of natural killer activity and aflatoxin B1 suppression of lymphocytic blastogenesis. PMID- 3109823 TI - Brief history of tongue inspection. PMID- 3109824 TI - Clinical study of 30 cases of subacute cutaneous lupus erythematosus. PMID- 3109825 TI - Congenital hypothyroidism: clinical analysis of 30 cases. PMID- 3109826 TI - Styloid process syndrome: length and palpation of the styloid process. PMID- 3109827 TI - An experimental study on acute compression of the internal capsule-basal ganglia region. PMID- 3109828 TI - Clinical significance of serum ferritin and leukocyte ferritin estimation in adult leukemias. PMID- 3109830 TI - Clinical and cytogenetic studies of a case of 45, X/46, XY Turner syndrome. PMID- 3109831 TI - Extrarenal juxtaglomerular cell tumor in bone: report of a case with review of the literature. PMID- 3109829 TI - External malleolus action on ankle stability in fibular resection. PMID- 3109832 TI - X-ray findings and pathological basis of bone fluorosis. PMID- 3109833 TI - Primary macroglobulinemia with myelofibrosis: report of a case. PMID- 3109834 TI - Opsonization activity in subacute hepatic failure and chronic liver disease. PMID- 3109836 TI - Dot-ELISA in the diagnosis of schistosomiasis. PMID- 3109835 TI - Dual atrioventricular nodal pathways associated with a nodoventricular tract inserting into the left ventricle. A case report. PMID- 3109837 TI - Platelet functions and factor VIII Ag in coronary heart disease. PMID- 3109838 TI - A preliminary study of the action of male hormone on high density lipoprotein cholesterol. PMID- 3109840 TI - Hereditary polydactylic dwarfism syndrome. PMID- 3109839 TI - Biphenyl-dimethyl dicarboxylate in treating and preventing hepatitis due to drug poisoning. PMID- 3109841 TI - Factors influencing the absorption of antineoplastic agents in intravesical instillation treatment of bladder tumors. An experimental and clinical study. PMID- 3109842 TI - Experimental Vibrio el-tor infected water fish breeding. Stressing reservoir establishment in loach and finless eels. PMID- 3109843 TI - Clinical appraisal of serum isozymes of LDH and GOT in the diagnosis of hepatobiliary diseases. PMID- 3109844 TI - Comparative study of schizophrenia treatment with electroacupuncture, herbs and chlorpromazine. PMID- 3109845 TI - Observations of clinical and chromosomal changes in a case of chronic granulocytic leukemia. PMID- 3109847 TI - Arteriovenous malformation of corpus callosum. Results of surgical treatment in 5 cases. PMID- 3109846 TI - Children's respiratory viral diseases treated with interferon aerosol. PMID- 3109848 TI - Carcinogenic effects of 131I, 132I and 125I on rat thyroids. A comparative pathological study. PMID- 3109849 TI - Elevated serum interleukin-2 receptor; increased in vitro immunoglobulin synthesis and lack of response to testosterone-enhanced in vitro interleukin-2 production in ankylosing spondylitis. AB - The pathogenesis of ankylosing spondylitis (AS) remains unknown, although previous studies have strongly suggested that it may result from immunological aberration. To further explore the pathogenetic mechanisms, in vitro syntheses of immunoglobulins and interleukin-2 (IL-2) by peripheral blood mononuclear cells (MNC), and the serum level of the interleukin-2 receptor (IL-2R) were studied in 35 patients with definite AS and in 28 healthy controls. MNC were cultivated in the presence of pokeweed mitogen (PWM) for seven days. Immunoglobulins in the supernatants were measured by rate nephelometer (Immunochemistry System Analyser II, Beckman.) In vitro synthesis of IL-2 was carried out by cultivating MNC in medium only; in medium containing physiological concentration of the male sex hormone i.e., testosterone 500 ng/dl and estradiol 2 ng/dl; and in medium containing physiological concentration of female sex hormone, i.e., testosterone 50 ng/dl and estradiol 20 ng/dl. IL-2 was quantitated using an IL-2-dependent cytotoxic T lymphoid cell line (CTLL). Serum IL-2R was measured using an IL-2R test kit (CELLFREE, T Cell Sciences, Cambridge, MA). The results showed: In vitro synthesis of IgG, IgA and IgM was significantly higher in AS than in controls; In vitro synthesis of IL-2 was significantly enhanced by testosterone in normal control, but not in AS; and Serum IL-2R was significantly elevated in patients with AS. These findings, viewed in conjunction with previous results here, lead to postulation that an inflammatory process, elicited in HLA-B27-positive males and caused by an infectious agent invading via the mucosa may both cause immunological abnormalities and provoke various symptoms and signs of AS. PMID- 3109850 TI - [Recent advances in surgery of tumors of the liver. Ultrasonic classification, specific nutritional aid and hepatic weight index during regeneration of the liver. Apropos of 104 cases]. PMID- 3109851 TI - [Chemotherapy of epithelial ovarian cancer: CHexUP versus thio-tepa]. PMID- 3109853 TI - Novel diarrhoea viruses. PMID- 3109852 TI - Primate evolution of a dispersed human repetitive DNA sequence. AB - A dispersed middle repetitive DNA sequence isolated originally from human chromosome 12 did not show homology with rodent DNA under standard conditions of Southern DNA blot analysis. The evolutionary relationship of this human repetitive DNA to that of other primates was investigated using three hybridization methods: DNA dot blot, Southern DNA blot analysis, and chromosome in situ hybridization. Homology with the human repetitive DNA was found throughout the suborder Anthropoidea, in fourteen ape and New and Old World monkey species. In addition, the human pattern of hybridization to noncentromeric regions of all chromosomes was seen. No hybridization by any of the three techniques was found in five species of the suborder Prosimii. The phenomenon of marked differences in sequence homology and copy number of dispersed repetitive DNA from closely related species has been observed in protozoans (Plasmodia), Drosophila, sea urchins, mice and the great apes (Hominoidea). We report here a similar phenomenon that may have occurred at an early stage in primate evolution. PMID- 3109854 TI - Astroviruses: human and animal. AB - The name astrovirus was used by Madeley and Cosgrove in 1975 to describe a small round virus (approximately 28 nm diameter) with star-like appearance on electron microscopy. It was first seen in faeces from a few children with gastroenteritis. An aetiological role in gastroenteritis has since been confirmed. The virus causes a mild illness after an incubation period of 3-4 days. Antibody studies indicate that infection is widespread and, in Britain, mainly occurs in the 2-5 year age group. Outbreaks occur in, for example, institutions and paediatric wards. The virus usually spreads by the faecal-oral route but food- or water borne outbreaks have occurred. Strains of astrovirus have been isolated from many animals including calf, lamb, pig, cat, dog, duck and turkey. The lamb strain can cause gastroenteritis but the bovine strain did not cause diarrhoea in gnotobiotic calves. Infected turkeys have scours, and infection in ducklings causes haemorrhagic hepatitis with a mortality up to 25%. Five human serotypes have been described, all antigenically distinct from the bovine and ovine strains. The human astrovirus does not replicate in conventional tissue cultures but undergoes a non-productive cycle in human embryo kidney cells, and productive replication in the presence of trypsin. It is a positive-strand RNA virus, which is acid stable (pH3), survives at 60 degrees C for five but not 10 minutes and, like the enteroviruses, resists inactivation by alcohols. It has a density of 1.35-1.37 g/ml in caesium chloride. PMID- 3109855 TI - [Experimental study on selenic blockage of primary hepatocarcinoma induced by aflatoxin B1 in rats]. PMID- 3109856 TI - [A food-borne outbreak of non-A non-B hepatitis]. PMID- 3109857 TI - [Pyrogen-induced fever in surgical patients]. PMID- 3109858 TI - Comparison of synchronized Chinese hamster ovary cells obtained by mitotic shake off, hydroxyurea, aphidicolin, or methotrexate. AB - Synchronized cell populations are necessary to study many aspects of cell biology. We have developed a method to obtain highly synchronized Chinese hamster ovary cell populations in S phase or G2 phase by utilizing mitotic selection followed by incubation with either hydroxyurea, aphidicolin, or methotrexate for 12 h. Flow cytometry analysis shows that the coefficient of variation in the spread of the cell population in S phase is as low as 6%. Drug toxicity studies compare the effects of the various drugs on G1 and S phase cells. The use of aphidicolin or hydroxyurea results in the most highly synchronized cell populations, but methotrexate yields inadequate synchronization. These results demonstrate that both aphidicolin and hydroxyurea are useful drugs for obtaining highly synchronized cell populations after an initial synchrony in mitosis. Aphidicolin is perhaps the best choice because of less toxicity to S phase cells when used in low concentrations. PMID- 3109859 TI - Quantitation of the binding, uptake, and degradation of fluoresceinylated neoglycoproteins by flow cytometry. AB - The fluorescence properties of the fluorescein residues bound to a protein are used to analyze by flow cytometry the neoglycoproteins' endocytosis mediated by membrane lectins of Lewis lung carcinoma cells (3LL cells). The quantum yield of fluorescein bound to a protein is dependent on the number of fluorophore molecules bound to a protein molecule and the pH of the environmental medium. The mean fluorescence intensity of a fluorescein molecule bound to a protein decreases when the number of fluorescein residues per protein molecule increases. However, after proteolytic digestion, the mean fluorescence intensity of a fluorescein molecule is constant and equal to that of free fluorescein. The binding of fluorescein-labeled alpha-glucosylated serum albumin to 3LL cells at 4 degrees C can easily be determined by flow cytometry because under these conditions the environmental pH is neutral, and the neoglycoprotein is not degraded. When the cells are incubated at 37 degrees C in the presence of a fluorescein-labeled neoglycoprotein, the fluorescence intensity of a cell is low because of the low pH of endosomes and lysosomes but is increased upon a postincubation at 4 degrees C in the presence of monensin, a proton/sodium ionophore. The extent of the proteolytic digestion of an endocytosed neoglycoprotein can be assessed by comparing, upon a monensin postincubation at 4 degrees C, the high cell-associated fluorescence of cells incubated in the absence of leupeptin (an inhibitor of lysosomal proteases) and the relatively low fluorescence intensity of cells incubated in the presence of leupeptin. PMID- 3109860 TI - Definitive combined modality therapy of carcinoma of the anus. A report of 30 cases including results of salvage therapy in patients with residual disease. AB - Thirty patients with epidermoid carcinoma of the anus, ranging in age from 40 to 89 years, were treated with combined chemotherapy (CT) and radiation therapy (RT) in lieu of abdominoperineal resection. Two courses of 5-FU (1000 mg/m2/day X four days) by continuous infusion and mitomycin-C (10-15 mg/m2 IV bolus on day 1 of each course) were given 3 to 4 weeks apart simultaneously, with whole pelvis RT to 4140 to 4500 cGy. Twenty-one of 28 patients had T3-T4 primaries and ten had positive nodes (N1). Two of the 30 patients were treated for local recurrence following surgical excision and one was treated immediately after local excision. Twenty-six of the 30 patients attained biopsy-confirmed complete remission. Four of the 30 patients demonstrated residual disease at completion of therapy but all subsequently achieved complete remission with additional nonsurgical treatment. One patient, initially treated for local recurrence following excision failed locally at four years and was salvaged with chemotherapy followed by abdominoperineal resection. No patient has experienced distant failure. Twenty seven of 30 patients were alive and disease free after 9 to 76 months of follow up and three died, disease-free, of unrelated causes. Acute toxicities were mild and did not necessitate interruption of treatment. A brisk perineal reaction and diarrhea were noted in all patients. Late complications were unusual. All patients were treated in a community-based, private practice setting. The authors conclude that combined CT-RT, as employed herein, represents a first-line curative treatment for the majority of patients with epidermoid anal carcinoma. For patients who demonstrate residual disease following this therapy, salvage regimens such as 5-FU infusion and cisplatin, or sequential MTX-5-FU-Leucovorin with additional synchronous RT should be employed before resorting to radical surgery. PMID- 3109863 TI - New devices in patients with diabetes mellitus. PMID- 3109861 TI - Limitations of indirect methods of estimating small bowel transit in man. AB - Experiments were carried out in healthy volunteers to explore the utility of a new [14C]lactulose breath test for measuring small intestinal transit time in man and to use this procedure to test whether two antidiarrheal agents, codeine and clonidine, alter small intestinal transit time during digestion of a liquid meal. In an initial validation study performed in 12 subjects (three studies in each subject), a liquid test meal containing 10 g [14C]lactulose was administered and the colonic entry time estimated from the time course of 14CO2 excretion in breath compared with that of H2 excretion. There was a fair correlation (r = 0.77; P less than 0.001) between results obtained by the two methods; both methods gave similar results, but 14CO2 output was delayed when compared to H2 output and was incomplete. The meal also contained xylose and [13C]glycine, permitting the duodenal entry time of the meal to be estimated by the appearance of xylose in blood and 13CO2 in breath, respectively. The same liquid meal was then used to examine the effect on small intestinal transit time (colonic entry time minus duodenal entry time) of codeine or clonidine. 99Tc-sulphur colloid was also added to the meal to permit a comparison of small intestinal transit estimated by imaging with that estimated by the 14CO2-lactulose breath test. 99Tc radioactivity appeared in the cecum (as assessed using gamma scintigraphy) about 2 hr before 14CO2 radioactivity appeared in breath; the correlation between transit time estimated by the two methods was moderate (r = 0.61; P less than 0.05). Based on the [14C]lactulose data, small intestinal transit time ranged from less than 1 to 3 hr for a liquid meal containing 10 g lactulose; within subject variation (coefficient of variation 17%) was considerably less than between-subject variation (coefficient of variation 56%). Codeine increased the small intestinal transit time significantly (from 2.7 +/- 0.3 hr to 5.0 +/- 0.9 hr; mean +/- SE), whereas clonidine did not alter small intestinal transit time, as estimated by the colonic entry time minus duodenal entry time. Neither drug influenced duodenal entry time. These results suggest that the [14C]lactulose breath test, which has only moderate accuracy, may have occasional utility as a convenient, noninvasive method for estimating small intestinal transit time in man. However, this study also suggests that indirect methods of estimating small bowel transit in man have limitations, variability, and possibly may lack the desired sensitivity. PMID- 3109862 TI - Differential effects of insulin- and proinsulin-induced hypoglycemia on pituitary hormone and catecholamine secretion. AB - The effects of insulin- and proinsulin-induced hypoglycemia on pituitary hormone and catecholamine secretion were compared in normal men to search for possible hypothalamic or pituitary inhibitory effects of proinsulin on glucocounterregulatory responses. When subjects received 0.1 U/kg i.v. human insulin and 25-38 micrograms/kg i.v. human proinsulin on separate occasions, plasma glucose decreased more rapidly after insulin, and the nadir was slightly lower, but integrated hypoglycemic responses were similar. Cortisol, growth hormone (GH), prolactin, epinephrine, and norepinephrine responses occurred more rapidly after insulin than after proinsulin. Peak and integrated cortisol, GH, and catecholamine responses to insulin and proinsulin were similar, but those of prolactin were reduced after proinsulin when compared with insulin by 42% (P less than .01) and 34% (P less than .05), respectively. When euglycemia was maintained by a variable glucose infusion rate after the injection of insulin and proinsulin, no differences were observed in plasma levels of any of the hormones. The intravenous injection of a dose of proinsulin (6 micrograms/kg), which did not produce hypoglycemia but was the molar equivalent of insulin used in the first protocol, failed to modify the GH or prolactin responses to a combined injection of GH-releasing hormone (1 microgram/kg) and thyrotropin-releasing hormone (500 micrograms). Our results indicate that the onset of pituitary hormone and catecholamine responses to hypoglycemia are related to the rate of plasma glucose decline, with the slower responses to proinsulin reflecting a more gradual onset of hypoglycemia. The magnitude of the cortisol, GH, and catecholamine responses, however, was comparable with proinsulin- and insulin induced hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109864 TI - A genetically engineered P450 monooxygenase: construction of the functional fused enzyme between rat cytochrome P450c and NADPH-cytochrome P450 reductase. AB - A hybrid cDNA encoding a fused enzyme consisting of rat cytochrome P450c and rat NADPH-cytochrome P450 reductase was constructed by combining the cytochrome P450c cDNA with the cDNA fragment encoding the protease-solubilized moiety of the NADPH cytochrome P450 reductase. The hybrid cDNA was inserted between the yeast alcohol dehydrogenase I promoter and terminator of the expression vector pAAH5 to yield expression plasmid pAMP19. Saccharomyces cerevisiae AH22 cells transformed with the expression plasmid pAMP19 produced a 130-kD protein reactive with both anti cytochrome P450c Ig and antireductase Ig. The yeast cells containing the fused enzyme exhibited about four times higher monooxygenase activity toward 7 ethoxycoumarin than those containing rat cytochrome P450c alone. The fused enzyme was purified from the yeast microsomal fraction by sequential chromatography with DEAE-cellulose and 2',5'-ADP Sepharose 4B columns. The preparation had an apparent molecular weight of 130 kD and the same sequence of the 10 amino terminal amino acids as that of rat cytochrome P450c. Spectral properties of the fused enzyme indicated the presence of a protoheme, flavin adenine dinucleotide, and flavin mononucleotide in the molecule. The reaction mechanism of the fused enzyme followed first-order kinetics. These results clearly indicate that the fused enzyme is a new self-catalytic P450 monooxygenase. Trypsin treatment of yeast microsomes containing the fused enzyme suggested that the P450 moiety is embedded in the microsomal membrane with the reductase moiety lying on the cytoplasmic side. PMID- 3109865 TI - Differential ability of various plasmid DNAs to sequester inhibitors of RNA polymerase III transcription. AB - Deletion mutants of the Drosophila tRNA(Arg) gene that lack A-box promoter sequences are not transcribed in several cell-free systems; however, they are actively expressed in vivo in Xenopus oocytes (Sharp et al., 1983a). We show that two A-box deletion mutants of the tRNA(Arg) gene can be transcribed by a HeLa cell-free transcription system if it is preincubated with various DNAs, indicating that an inhibitor is responsible for the lack of mutant tRNA gene transcription. Optimal mutant transcription rescue, and presumably optimal binding of inhibitor, is facilitated by the presence of an active RNA polymerase II promoter in the preincubating DNA. Plasmid DNAs containing RNA polymerase III or weak RNA polymerase II promoters are of intermediate rescue efficiency, and pBR322 DNA is least efficient. Competition studies indicate that the stability of the inhibitor-DNA complex formed initially is apparently increased if the preincubating DNA contains an active RNA polymerase II promoter. Thus, HeLa whole cell lysates contain a specific inhibitor(s) of RNA polymerase III transcription that primarily affects weakened RNA polymerase III promoters (e.g., A-box deletion mutants) and binds preferentially to DNAs containing an active RNA polymerase II promoter. Yet this apparent sequestration of inhibitor by Class II templates does not appear to inhibit their subsequent transcription by RNA polymerase II. These data raise the possibility that there may be interactions between the RNA polymerase II and III transcription machinery. PMID- 3109866 TI - Molecular cloning of an amylase gene of Bacillus circulans. AB - An amylase gene of Bacillus circulans was cloned in B. subtilis and its nucleotide sequence was determined. The putative proamylase consists of 528 amino acids, which correspond to a molecular weight of 58,776. Homologous regions with other amylases of Bacillus species were found. A sigma 55-type promoter is located at about 250 bp upstream from the starting codon. This promoter was also functional in Escherichia coli, and able to express beta-galactosidase activity. PMID- 3109867 TI - [Integration and expression of the human dihydrofolate reductase gene in the Bacillus subtilis chromosome]. PMID- 3109868 TI - [Non-steroidal anti-inflammatory agents increase intestinal permeability]. AB - 51Cr-EDTA activity was measured in urine and blood of patients receiving non steroidal anti-inflammatory (NSA) drug treatment and of healthy subjects and other patients (controls), after oral intake of 51Cr-EDTA, for the purpose of deciding whether NSA treatment increases urinary excretion of oral 51Cr-EDTA as an expression of increased intestinal permeability. 51Cr-EDTA activity in urine and blood of patients with rheumatoid arthritis (13) being treated with NSA was significantly higher (similar to results in 13 patients with Crohn's disease) than that of a control group (14) of patients with rheumatoid arthritis without such treatment (9) and patients without rheumatic disease (5). Both in patients with rheumatoid arthritis receiving NSA drugs and patients with Crohn's disease there was a highly significant correlation between urinary and blood activity. There was no effect of NSA drugs on renal function. The results indicate that NSA drugs increase interenterocytic permeability to an extent comparable to permeability abnormalities in Crohn's disease. PMID- 3109869 TI - [Calcium antagonists in experimental and clinical gastroenterology]. PMID- 3109870 TI - [Percutaneous endoscopically controlled gastrostomy]. PMID- 3109871 TI - Arachidonic acid metabolism and inflammation: therapeutic implications. Proceedings of a symposium. Paris, 28-30 March 1986. PMID- 3109872 TI - The role of arachidonic acid metabolites in renal homeostasis. Non-steroidal anti inflammatory drugs renal function and biochemical, histological and clinical effects and drug interactions. AB - Prostaglandins (PG) E2 and I2 have a number of effects on renal function, such as causing vasodilatation, increasing the glomerular filtration rate, sodium chloride excretion, water excretion, and stimulating renin secretion. Studies in dogs have shown that reductions in renal blood flow associated with angiotensin II administration are accompanied by increased synthesis of vasodilatory PGE2 followed by a compensatory increase in blood flow. Moreover, in rats and dogs, non-steroidal anti-inflammatory drugs (NSAIDs) markedly augment the reductions in renal blood flow associated with angiotensin II administration. Clinical use of NSAIDs can induce 1 of 2 types of renal syndromes in patients with certain predisposing conditions. These syndromes are ischaemic acute renal failure and papillary necrosis or, rarely, an idiosyncratic reaction. It is believed that the effects of cyclo-oxygenase inhibitors on renal function are most important in patients with these predisposing conditions because in many of these conditions there is increased synthesis of renal PGE2 and PGI2 to compensate for abnormally high plasma concentrations of vasoconstrictor hormones. Angiotensin II produces a concentration-dependent contraction of isolated rat glomeruli or mesangial cells which is potentiated by pretreatment with indomethacin or meclofenamate. Pretreatment with arachidonic acid, or addition of exogenous PGE2, inhibits the angiotensin-mediated glomerular contraction. Stable endoperoxide analogues, which mimic the effects of thromboxane A2, induce a similar glomerular contraction to angiotensin. Similar findings were recorded using isolated rat mesangial cells. Mesangial cell contraction is believed to reduce the filtration surface area of the glomerulus and, therefore, the glomerular filtration rate. In these cells angiotensin II not only induces contraction but also increases the rate of synthesis of PGE2. Associated with the acute reduction in renal function after induction of an immune glomerular nephritis in rats, there is a marked increase in glomerular thromboxane synthesis. The thromboxane synthetase inhibitor dazoxiben inhibits this increase and prevents the acute renal changes which occur in untreated animals during the first 3 hours after antibody injection. However, thromboxane synthetase inhibitors have no influence on renal function when nephrotoxic serum nephritis has been established for 14 days. In conclusion, maintenance of adequate renal function would seem to be dependent on a balance of substances causing mesangial relaxation (PGE2 and PGI2) and contraction (thromboxanes, endoperoxides and leukotrienes).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3109873 TI - Effects of mycotoxins in cultured kidney cells: cytotoxicity of aflatoxin B1 in Madin-Darby and primary fetal bovine kidney cells. AB - The cytotoxicity of aflatoxin B1, a fungal metabolite and an important food contaminant, was evaluated in an established cell line, Madin-Darby bovine kidney (MDBK) cells, and in primary fetal bovine kidney (PFBK) cells. Cells were grown in monolayers and treated with media containing AFB1 for 24 hr. Both culture systems were sensitive to the chemical; the PFBK cultures were approximately four times more susceptible to the cytotoxic effect. Cell multiplication decreased in both systems in long-term cultures. Adherence of MDBK cells was only slightly reduced at the toxic concentrations of the chemical. Electron microscopy revealed condensation of chromatin, separation of nuclei from the cytoplasm, cytoplasmic vacuolization, and loss of surface microvilli. Results indicated differential sensitivity of the two culture systems. PMID- 3109874 TI - Fate of 2,5,4'-trichlorobiphenyl in outdoor ponds and its uptake via the food chain compared with direct uptake via the gills in grass carp and rainbow trout. AB - A field experiment was carried out to investigate the fate and the extent to which food chain transfer of a PCB congener (2,5,4'-trichlorobiphenyl; 3-CB) could affect its potential for bioaccumulation. Three 35-m3 ponds were each stocked with 25 rainbow trout (a carnivore) and 20 grass carp (a herbivore). 3-CB was supplied to each pond at a nominal concentration of 14 micrograms liter-1. Samples of water, sediment, grass carp, rainbow trout, aquatic plants, and invertebrates were removed at intervals from 0 to 28 days after treatment and residues of 3-CB were determined using gas-liquid chromatography with electron capture detection. The fate of 3-CB in the ponds was determined by transport rather than degradation processes. Evaporation accounted for 86-87% loss and sorption onto sediment and biota for 11-12% loss of 3-CB from the pond water after 28 days. The kinetics of transport between water, air, sediment, and biota were studied after fitting the data to a three-compartment model. This model was used to calculate rates of evaporation (ke) and sorption. The calculated value for ke was in good agreement with predictions based on fundamental relationships between Henry's constant, windspeed, and ke. Residues of 3-CB in rainbow trout accumulated to a significantly greater extent (P less than 0.05) than in grass carp. This difference could not be explained by differences in growth rates, distribution of lipids, or by a difference in rates of metabolism. The most plausible explanation is that there was a difference in accumulation of 3-CB residues via the food chain. This experimental work supports the conclusion, suggested by a modeling approach of other workers, that food chain accumulation of PCBs can be an important route for uptake when environmental concentrations are very low. PMID- 3109875 TI - [Sweet bulimia, salty bulimia. 2 syndromes]. AB - We report the psychopathological study of 20 subjects with the Bulimia syndrome (DSM III criteria) specifying affective, emotional state and psychiatric symptoms associated with the eating disorder. Evaluation was made using self-rating questionnaires, anxiety and depression rating scales and specific rating scales for various clinical dimensions (impulsivity and mood). Two groups of subjects differing from one another on their elective appetite and taste for two types of food (sweet versus salty) are distinguished. Clinical characteristics of each group are different: Carbohydrate bulimics are more impulsive, dysphoric, make much greater use of medications, drugs, and alcohol than salted food bulimics do. Patients of the second group are more anxious and emotionally blunted. Anorexia nervosa was more often present in their past. The two groups differ also in their responses to serotoninergic and noradrenergic medications used here in open trial. These results are consistent with literature data on carbohydrate metabolism, impulsivity disorders, depression and cerebral serotonin. PMID- 3109876 TI - Identification and characterization of thyrotropin-releasing hormone precursor peptides in rat brain. AB - The sequence of rat hypothalamic pro-TRH, deduced by sequencing of cDNA, contains five copies of the TRH progenitor sequence Gln-His-Pro-Gly flanked by paired basic amino acid sequences. The TRH prohormone also contains leader and trailer sequences and four intervening sequences. We have developed two RIAs against synthetic peptides corresponding to sequences within the deduced pro-TRH sequence and have used these assays to identify and partially characterize four pro-TRH derived peptides distinct from TRH in extracts of rat brain tissue. Two of these peptides contain incompletely processed TRH sequences; the other two peptides are probably derived from the N-terminal leader sequence. The presence of these authentic pro-TRH-derived peptides indicates that pro-TRH may give rise to a family of peptides other than TRH, some of which may be of biological significance. PMID- 3109877 TI - Enkephalin convertase in the gastrointestinal tract an associated organs characterized and localized with [3H]guanidinoethylmercaptosuccinic acid. AB - Enkephalin convertase (carboxypeptidase EH; EC 3.4.17.10), a carboxypeptidase B like enzyme which processes hormone and neuropeptide precursors, has been characterized in the gastrointestinal tract, submandibular gland, and pancreas using a binding assay with [3H]guanidinoethylmercaptosuccinic acid. Binding to homogenates of the membrane and soluble fractions of stomach, small intestine, colon, and submandibular gland is saturable, with Kd values of about 2 nM. Partial purification of the membrane fractions reveals a Co+2-stimulated carboxypeptidase B activity which is not detectable in crude homogenates. In vitro autoradiography with [3H]guanidinoethylmercaptosuccinic acid localizes enkephalin convertase to the epithelial cells of the stomach, colon, and intestine, the islet cells of the pancreas, and the acinar cells of the submandibular gland. This localization contrasts to the distribution of enkephalins and other neuropeptides in the gastrointestinal tract and associated organs, suggesting that enkephalin convertase may serve functions other than neuropeptide and prohormone processing. PMID- 3109878 TI - Changes in thyrotropin (TSH) carbohydrate structure and response to TSH-releasing hormone during postnatal ontogeny: analysis by concanavalin-A chromatography. AB - We have studied the carbohydrate structure of TSH as well as its response to TRH during postnatal ontogenesis in the rat using Concanavalin-A (Con A)-Sepharose chromatography of labeled glycopeptides. Pituitaries from neonatal (5-day-old) rats with low levels of endogenous TRH and mature (56-day-old) rats were incubated for 24 h in medium containing [3H] glucosamine in the presence or absence of 10(-7) M TRH. Both intracellular and secreted TSH were immunoprecipitated, treated with Pronase to generate glycopeptides, and analyzed by chromatography on Con A-Sepharose. The total amount of [3H]glucosamine-labeled TSH was greater per pituitary in mature rats compared to that in neonatal rats (P less than 0.05), while there was no significant difference between the groups in the concentration of total labeled TSH per microgram pituitary DNA. RIA determination of total TSH was greater in the older animals than in the younger animals when normalized both per pituitary and per microgram pituitary DNA (P less than 0.01 and P less than 0.02, respectively). However, for both labeled and unlabeled TSH the percentage of TSH secreted was greater in mature rats than in neonatal rats (P less than 0.02 and P less than 0.01, respectively), indicating a less active hormonal secretory process in the younger animals. In control animals, the proportion of labeled TSH glycopeptides that did not bind to Con A was greater in 56- than in 5-day-old animals for both intrapituitary and secreted forms (P less than 0.01), reflecting a shift toward more multiantennary and/or bisected biantennary complex carbohydrate structures in the older animals. In response to TRH in vitro, the total amount of labeled secreted TSH was increased more than 2-fold in both 5-day-old (P less than 0.05) and 56-day-old (P = NS) animals. However, there was a marked difference in the glycopeptide distribution between these two ages. Five-day-old animals showed a small but not significant decrease in the percentage of secreted TSH glycopeptides that bound to Con A Sepharose, while 56-day-old animals had a specific increase in the glycopeptide fractions that bound and corresponded to biantennary complex and/or unusual hybrid forms (P less than 0.01). These studies in the rat suggest differences in TSH carbohydrate structure and secretion as well as a differential response to TRH during postnatal ontogenesis. PMID- 3109880 TI - In vitro evidence for short-loop gonadotropin feedback on gonadotropin-releasing hormone neurons harvested from adult male rats. AB - GnRH neurons were harvested from adult male rats in order to determine if LH or FSH directly altered the modalities of GnRH release and/or cellular GnRH content. Cultures received vehicle, 25 ng/ml LH, 125 ng/ml LH, 25 ng/ml FSH, or 125 ng/ml FSH, and media samples were collected before treatment, during the treatment pulse, and at 24 h post treatment; cellular GnRH content was determined 48 h post treatment. Both LH treatments used in this study acutely increased the frequency of spontaneous GnRH pulses and the mean media GnRH concentration. Further, neurons treated with an LH pulse exhibited large amplitude GnRH pulses during the treatment period. In contrast, FSH treatments had no effect on mean media GnRH concentrations and the 25 ng/ml FSH treatment did not alter neurosecretory modalities of spontaneous GnRH release. The neurons which received 125 ng/ml FSH did however exhibit large amplitude GnRH pulses during the gonadotropin pulse. This latter treatment was also associated with reduced cellular GnRH content whereas neuronal GnRH content was not affected by the 25 ng/ml FSH treatment or by LH treatments. These results suggest that both LH and FSH may interact directly with GnRH neurons to elicit a change in the modalities of GnRH release and that FSH may also act to reduce cellular GnRH content. PMID- 3109879 TI - Evidence for stimulatory noradrenergic and inhibitory dopaminergic regulation of oxytocin release in the lactating rat. AB - The present experiments tested the involvement of central catecholaminergic systems in the suckling-induced release of oxytocin (OT) during lactation in the rat. In the first experiment, female rats in midlactation were separated from their offspring for 4 h and then allowed to suckle their litters for 30 or 60 min or to remain nonsuckled. The turnover rates of norepinephrine (NE) and dopamine (DA) were calculated from the rate of decline after synthesis inhibition. Suckling decreased the turnover rate of DA in the median eminence and in the neurointermediate lobe of the pituitary gland. Suckling increased the turnover rate of NE in the rostral paraventricular and supraoptic nuclei, areas that contain most of the OT cells that project to the neural lobe of the pituitary, and in the interstitial nucleus of the stria terminalis, but not in the arcuate or caudal paraventricular nuclei, median eminence, or neurointermediate lobe. In a second experiment, midlactating females received intracerebral microinjections of the catecholamine neurotoxin 6-hydroxydopamine or of vehicle into the vicinity of the paraventricular and supraoptic nuclei 1 week before a suckling test. The release of OT was completely prevented in 6-hydroxydopamine-treated animals, and NE was significantly decreased in the paraventricular, supraoptic, and arcuate nuclei. In a third study, the increase in plasma OT in response to suckling was prevented by stimulation of DA receptors with bromocriptine, while blockade of DA receptors with domperidone significantly increased plasma OT levels in nonsuckled lactating rats. These results suggest that suckling stimulation activates the noradrenergic innervation to the rostral paraventricular nucleus and to the supraoptic nucleus, which exerts an excitatory influence on the release of OT and decreases activity of the tuberohypophyseal DA system, which provides a tonic inhibitory influence over the secretion of OT. PMID- 3109881 TI - Control of prolactin release induced by suckling. AB - In the present study, the role of dopamine and TRH in suckling-induced PRL release was investigated. Bupropion, a dopamine reuptake blocker, increased hypophysial stalk dopamine levels and inhibited suckling-induced PRL release. A short period of suckling, thought to induce a transient decrease in hypothalamic dopamine release, led to higher PRL levels following an iv injection of TRH than in rats which had not nursed their young for a short period after 4- to 6-h separation. These results, in combination with previous data, suggest that a decrease in hypothalamic dopamine release is important for suckling-induced PRL release. Increased PRL release may be in part due to an augmented hypothalamic release of TRH. Since serotonergic mechanisms seem involved in TRH release, lactating rats were treated with drugs acting on serotonergic pathways. Parachlorophenylalanine and pizotifen did not alter suckling-induced PRL release. Methysergide, a serotonin receptor blocker, prevented this PRL release when administered ip but not when injected into the lateral brain ventricle. Since methysergide is converted peripherally into metabolite(s) with dopamine agonistic activity, its effect on suckling-induced PRL release may be due to this action, rather than to its action on serotonin receptors. Thus, these data do not indicate that serotonergic mechanisms are important for suckling-induced PRL release. Passive immunization against TRH inhibited suckling-induced PRL release, indicating that TRH is a hypophysiotropic mediator of this PRL release. PMID- 3109882 TI - Localization of thyrotropin-releasing hormone prohormone messenger ribonucleic acid in rat brain in situ hybridization. AB - We studied the distribution of pro- TRH mRNA in rat brain by in situ hybridization histochemistry using radiolabeled single stranded cRNA probes to confirm the hypothesis that the TRH precursor is distributed beyond regions that contain immunoreactive TRH. All regions of the central nervous system previously recognized to contain TRH showed hybridization. Hypophysiotropic neurons in the medial parvocellular division of the paraventricular nucleus showed more intense hybridization than anterior parvocellular division cells, suggesting regional differences in expression. In addition, regions not previously recognized to contain TRH in neuronal perikarya by immunocytochemistry showed specific hybridization for pro-TRH mRNA. These include cells in the olfactory bulbs, dorsal motor nucleus of the vagus, ventrolateral periaqueductal gray, reticular nucleus of the thalamus, and anterior commissural nucleus. Only a single hybridizing band was observed on Northern blots of RNA extracts of the periaqueductal gray and reticular nucleus, identical to that seen in extracts of the paraventricular nucleus. The appearance of pro-TRH mRNA in neurons not previously recognized to contain TRH but which contain the prohormone suggests that non-TRH peptides within the TRH precursor may be preferentially expressed in certain regions of the brain. PMID- 3109883 TI - The effect of free radicals on hepatic 5'-monodeiodination of thyroxine and 3,3',5'-triiodothyronine. AB - Free radicals have been implicated in many pathological processes, including ischemia, inflammation, and malignancy. Since a reduction in extrathyroidal outer ring monodeiodination of T4 and rT3 occurs in virtually all systemic illnesses, we have studied the effect of free radicals on iodothyronine (T4 and rT3) 5' monodeiodinating activity (MA) of liver tissue in vitro. Rat liver microsomes or homogenate were preincubated in Tris buffer for 30 min with a free radical generating system (FRGS) and then incubated with T4 (2.5 microM) or [125I]rT3 (0.4 nM) and dithiothreitol (DTT; 5-20 mM with T4 and 20-150 mM with [125I]rT3) in the same buffer for 10 or 30 min. T3 generated during incubation was quantified by RIA of ethanol extracts of the incubation mixture. 125I generated from [125I]rT3 was quantified after precipitation of the incubation mixture with trichloroacetic acid or by paper chromatography. Free radicals caused 55% or more reduction in hepatic T4 MA and 44% or more reduction in rT3 MA in various experiments. The inhibition of hepatic rT3 MA after incubation with FRGS persisted despite removal of FRGS and washing of microsomes preincubated with FRGS before studying the MA. However, inclusion of DTT (1-60 mM) during preincubation of tissue with FRGS prevented the FRGS-induced inhibition of rT3 MA. Depletion of the iodothyronine substrate did not occur when FRGS inhibited T4 and rT3 5'-monodeiodination. Free radical scavengers, i.e. superoxide dismutase (600 IU/ml), catalase (300 U/ml), tocopherol (10 mg/ml), thiourea (0.15 M), and tert-butanol (0.15 M), all significantly reduced the inhibition of hepatic rT3 MA caused by FRGS. The FRGS-induced inhibition of hepatic T4 MA was reduced by the same doses of tocopherol, thiourea, and tert-butanol, but not by superoxide dismutase or catalase. Since free radicals may effect tissue damage by lipid peroxidation and since the latter results in generation of malondialdehyde (MDA) as a by-product of the reaction, we studied MDA by its reaction with 2 thiobarbituric acid. Incubation with FRGS caused an approximately 100-fold increase in MDA formation in liver microsomes. Serum MDA was significantly higher in 16 NTI patients than in 8 normal subjects and also higher in turpentine oil injected rats [an experimental model of nonthyroidal illness (NTI)] than in saline-injected control rats. The data suggest that generation of free radicals may contribute to the reduced extrathyroidal 5'-monodeiodination of T4 and rT3 in NTI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3109884 TI - Modulation of gonadotropin secretion by corticosterone: interaction with gonadal steroids and mechanism of action. AB - The effects of corticosterone (B) on pituitary responsiveness to LHRH and on gonadal steroid modulation of gonadotropin secretion were investigated using primary cultures of rat pituitary cells. Cultures were treated for 2 days with steroids and then challenged with LHRH for 4 h. B inhibited LH secretion, increasing the EC50 for LHRH from 1.40 to 4.96 nM. The reduction in LH release was accompanied by an increase in cell LH, so that the total amount of LH present in the cultures was unchanged. The EC50 for the effect of B on LH secretion was 0.57 microM. B increased the total amount of FSH present in the cultures. At high concentrations of B (10-100 microM), this effect was associated with an increase in FSH secretion. Testosterone inhibited LH secretion in both the absence and the presence of B. B had no effect in the presence of maximal concentrations of testosterone but augmented the inhibitory effect of lower concentrations. Estradiol (E) stimulated LH secretion in both the absence and the presence of B. However, the stimulatory effect of E was reduced by B, so that cultures treated with both B and E secreted no more LH than untreated cultures. B inhibited the LH secretory responses to Ca2+ influx and protein kinase C activation but did not affect the response to arachidonic acid, suggesting that the mechanism of B action may involve an inhibition of arachidonic acid release. Together these results indicate that the inhibitory effects of stress on reproduction are mediated at least partially by the inhibitory effects of B on LH secretion. PMID- 3109885 TI - Suppression of luteal function by a luteinizing hormone-releasing hormone antagonist during the early luteal phase in the stumptailed macaque monkey and the effects of subsequent administration of human chorionic gonadotropin. AB - In previous studies a single sc injection of the LHRH antagonist [N-Ac-D Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10 ]LHRH during the luteal phase of the stumptailed macaque menstrual cycle caused a transient suppression of serum LH and progesterone concentrations. To investigate whether a more prolonged suppression of LH release during the early luteal phase could result in a sustained suppression of progesterone, 10 monkeys were treated with 3 consecutive daily injections of 300 micrograms LHRH antagonist/kg beginning on days 0 (n = 2), 1 (n = 1), 2 (n = 1), 3 (n = 2), 4 (n = 2), and 5 (n = 2) after the LH surge. When the antagonist was administered on the day of the LH surge, serum concentrations of bioactive LH were still elevated on the following day, but then fell to low levels. Serum progesterone concentrations were subnormal in these monkeys for the next 10 days, but recovered toward the late luteal phase. In the 8 monkeys receiving antagonist starting between days 1-5 after the LH surge, serum concentrations of bioactive LH were suppressed to near the detection limit of the assay for 4 days after the first injection. Seven of the 8 monkeys demonstrated a progressive decline in serum progesterone concentrations to undetectable values which remained for the duration of the luteal phase. In the remaining monkey the decline in progesterone was less marked; this animal presented a normal progesterone profile 3 days after the last antagonist injection. Premature menses occurred in all 8 monkeys; the next ovulation occurred 18.9 +/- 0.3 days after the last antagonist injection. To test luteal function after antagonist treatment during the early luteal phase and to mimic the rescue of the corpus luteum during a fertile cycle and assess the contraceptive effects of antagonist, hCG in daily doses of 30, 60, 90, 180, and 360 IU was administered starting on day 7 of the luteal phase to monkeys previously treated with three daily injections of 300 micrograms antagonist/kg during the early luteal phase. Control monkeys received hCG injections alone. In the controls, hCG administration elevated serum progesterone concentrations to 15 20 ng/ml. In three monkeys in which antagonist administration did not commence until day 5 or 6, hCG overcame the suppressive effect of the antagonist. However, in seven monkeys in which antagonist administration began on days 1-4, hCG caused only a small progesterone rise (maximal range, 1.8-4.9 ng/ml), about 20% of that observed in control monkeys receiving hCG.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3109886 TI - Prostaglandin endoperoxide synthase in rat ovarian follicles: content, cellular distribution, and evidence for hormonal induction preceding ovulation. AB - These studies were undertaken to determine if the content of prostaglandin endoperoxide (PGH) synthase (PGS) was regulated in rat ovarian follicles in a time-, tissue-, and dose-dependent manner. For quantitation and localization of the enzyme by immunoblot and immunofluorescent analyses, respectively, a polyclonal antibody to highly purified (95%) ovine seminal vesicle PGS [mol wt, (Mr), 72,000] was generated in a rabbit, and an immunoglobulin G fraction of the antiserum was purified by elution from a PGS affinity resin. Soluble cell extracts were prepared from: 1) small antral (SA) and preovulatory (PO) rat follicles before and at selected time intervals after exposure to increasing doses (0.25-10.0 IU) of hCG, 2) granulosa and thecal cells of these same follicles, and 3) granulosa cells of hypophysectomized (H) rats before and after treatment with estradiol (HE), estradiol and FSH (HEF), and 10 IU hCG. Immunoblot analyses demonstrated that the content of PGS (Mr, 72,000) was low (negligible) in granulosa and thecal cells of SA and PO follicles, was induced preferentially (approximately 15-fold) in granulosa cells between 1 and 7 h after hCG treatment (0.5, 2.0, or 10 IU), and declined between 12-24 h after administration of 10 IU hCG, reaching undetectable amounts in corpora lutea isolated 48 h after hCG treatment. PGS (Mr, 72,000) was also induced by 10 IU hCG in granulosa cells of HEF rats, but was low in granulosa cells of H, HE, and HEF rats. In contrast, prostacyclin synthase was present in granulosa cells of preantral (H and HE rats), SA, and PO follicles, was not induced by hCG, and was highest in thecal cells. Immunofluorescent analyses confirmed both the tissue-specific localization and induction of PGS in granulosa cells of rat PO follicles treated with 10 IU hCG and the subcellular fractionation analyses showing that the PGS that was induced by hCG was localized primarily to a membrane (plasma membrane?) fraction of granulosa cells. Immunofluorescent data also demonstrated immunoreactive PGS in the vascular tissue of the rat corpus luteum but not in the luteal cells. Results of these studies document unequivocally that the synthesis of prostaglandins that is increased by LH/hCG in rats preceding ovulation is associated with an increased PGS content, that induction of the induced enzyme is transient, and that the enzyme is primarily localized to granulosa cell membrane fractions. PMID- 3109887 TI - Involvement of phospholipase A activity in the plasma membrane of the rat corpus luteum during luteolysis. AB - Plasma membrane samples prepared from corpora lutea (CL) of control and prostaglandin F2 alpha-treated rats were incubated with radiolabeled phosphatidylcholine for 90 min at 40 C with 1 mM CaCl2 to test for the presence of phospholipase A2 activity. At the end of the incubation period, labeled arachidonic acid cleaved from the 2 position of the phospholipid moiety had accumulated to 10.7 +/- 2.4% (mean +/- SE) of the initially added radioactivity in the prostaglandin F2 alpha-treated samples, with 3.7 +/- 1.2% appearing in the controls. Arachidonic acid production was inhibited by calcium chelation and by the phospholipase A2 inhibitor bromophenacyl bromide, indicating heightened activity of phospholipase A2 in CL plasma membranes undergoing regression. Unexpectedly, radiolabeled lysophosphatidylcholine was produced in regressed membrane samples at a similar rate, suggesting the induction of phospholipase A1 activity as well. To determine if the membrane rigidification that occurs with regressed membrane samples under the same incubation conditions is caused by the hydrolysis products of phospholipase activity, fluorescence polarization experiments with the probe trans-parinaric acid were conducted. Washing of incubated membrane samples with fatty acid-free BSA, which selectively removes free fatty acids and lysophosphatides from the bilayer, resulted in a restoration of the fluidity to levels recorded at the onset of the incubation. These results suggest that the previously described decreases in CL plasma membrane fluidity and hCG binding in vitro during luteolysis are caused by a synergistic effect of calcium ion and hydrolysis products of phospholipase A activity. PMID- 3109888 TI - The effect of cysteamine, cystamine, and the structurally related compounds taurine, N-acetyl-cysteine, and D-penicillamine on plasma prolactin levels in normal and estrogen-primed hyperprolactinemic rats. AB - Studies were undertaken to evaluate the effects of cysteamine (CSH), cystamine (CS-S), N-acetyl-cysteine, D-penicillamine, and a major metabolite of CSh, taurine, on plasma PRL levels in normal and estrogen-primed hyperprolactinemic rats. Both CSH and CS-S caused a marked decrease in plasma PRL concentration in hyperprolactinemic rats. The effects of CSH and CS-S lasted for at least 6 h but returned toward pretreatment levels 24 h later. In normal rats a fall in basal plasma PRL concentration was not readily observed but after stimulation with TRH or metaclopramide, PRL secretion elicited by these stimuli was markedly inhibited by CSH and CS-S. The response to TRH or MCP 24 h after treatment with CSH was variable with CS-S appearing to cause an unexpected increase in PRL release in response to TRH or metaclopramide. The structurally related compounds, taurine, N acetyl-cysteine, and D-penicillamine did not cause any reduction of plasma PRL levels in hyperprolactinemic rats. This may be due, in the case of taurine, to a loss of the free sulfydryl group, in the case of N-acetyl-cysteine, a change in basicity because of a carboxyl group and derivatization of the amino group and D penicillamine, again a change in basicity due to a free carboxyl group as well as an altered structural relationship between the free amino and sulfydryl groups. These studies indicate that CSH and CS-S by possible reduction to CSH cause a reversible depletion in plasma PRL in normal and hyperprolactinemic rats. Because both substances inhibit different receptor-mediated stimuli, their mechanism of action is likely to be mediated at a common locus involved with the synthesis and release of PRL. PMID- 3109889 TI - Organization of multispecific DNA methyltransferases encoded by temperate Bacillus subtilis phages. AB - B. subtilis phage rho 11s codes for a multispecific DNA methyltransferase (Mtase) which methylates cytosine within the sequences GGCC and GAGCTC. The Mtase gene of rho 11s was isolated and sequenced. It has 1509 bp, corresponding to 503 amino acids (aa). The enzyme's Mr of 57.2 kd predicted from the nucleotide sequence was verified by direct Mr determinations of the Mtase. A comparison of the aa sequence of the rho 11s Mtase with those of related phages SPR and phi 3%, which differ in their methylation potential, revealed generalities in the building plan of such enzymes. At least 70% of the aa of each enzyme are contained in two regions of 243 and 109 aa at the N and C termini respectively, which are highly conserved among the three enzymes. In each enzyme, variable sequences separate the conserved regions. Variability is generated through the single or multiple use of related and unrelated sequence motifs. We propose that the recognition of those DNA target sequences, which are unique for each of the three enzymes, is determined by these variable regions. Evolutionary relationships between the three enzymes are discussed. PMID- 3109890 TI - Cloning and light regulation of expression of the phycocyanin operon of the cyanobacterium Anabaena. AB - The biliprotein phycocyanin (PC) is a major constituent of the light-harvesting apparatus of cyanobacteria and red algae. A DNA fragment encoding the beta and alpha subunits of PC was isolated from a genomic library of the cyanobacterium Anabaena 7120 DNA. The single-copy PC genes are part of a larger operon which consists of five open reading frames (ORFs) encoding, in order, the beta and alpha subunits of PC, two linker polypeptides associated with PC in phycobilisome rods, and a fifth ORF, which may encode a linker polypeptide involved in attachment of the phycobilisome rod to the core of the structure. The operon yields three major transcripts, the first of which (1.4 kb) encodes only the PC subunits. A second (3.6 kb) encodes all five ORFs, and appears to arise from partial read-through of a terminator following the PC subunit genes. The third transcript (1.4 kb) encodes the last two ORFs. The relative levels of the three transcripts in vivo are modulated by light intensity, but they are not altered by the removal of fixed nitrogen from the growth medium. The site of light regulation appears to be the terminator following the PC genes, rather than a promoter. PMID- 3109891 TI - Somatic point mutations in unrearranged immunoglobulin gene segments encoding the variable region of lambda light chains. AB - Somatic point mutations are usually found in the coding and flanking regions of functionally and aberrantly rearranged immunoglobulin variable region gene segments. Mutations in the unrearranged V gene segments of myelomas or hybridomas have not been described so far. We have cloned and sequenced unrearranged V lambda gene segments from several cell lines. There were no nucleotide changes in four unrearranged V lambda segments: one V lambda 1 from a lambda 3-producing hybridoma and one V lambda 2 from a lambda 1-producing myeloma (J558) and two V lambda 2 from a kappa-producing myeloma (P3X63). However, we found somatic mutations in the unrearranged V lambda segments from the lambda 2-producing myeloma MOPC315. The unrearranged V lambda 1 gene segment had two mutations in the coding region and the unrearranged V lambda 2 had one mutation in the 3' flanking region. We also cloned and sequenced the unrearranged J lambda and C lambda gene segments of MOPC315 and found no sequence alterations. This is consistent with the notion that the overall mutation rate is not higher in this cell line. Therefore, we suggest that the somatic hypermutation system can use unrearranged V gene segments as substrates. The extensive sequencing required for this work revealed a number of errors in the reported nucleotide sequences of the Ig lambda locus in BALB/c mice. PMID- 3109892 TI - Respiratory drive and timing before and during CO2 inhalation in infants anaesthetized with halothane. AB - To evaluate respiratory drive and timing in 11 spontaneously breathing infants anaesthetized with halothane, ventilation was followed before and during CO2 provocation, and occlusion tests were performed. All infants were younger than 6 months of age and their weights ranged from 3.8 to 7.5 kg. All measurements were performed prior to surgery. Tidal volumes (VT) were followed by pneumotachography and end-tidal CO2 concentration [E'CO2) by an in-line capnograph. Occlusion pressure curves were biphasic with an initial fast phase (pressure: P degree fast, duration: T degree fast) followed by a slower phase to the maximal occluded infra-airway pressure (P degree max, T degree max). During CO2 breathing, mean values of P degree fast increased by 75% (P less than 0.001) and of P degree max by 73% (P less than 0.001) compared with at CO2-free breathing. The slope of the fast phase (delta P/delta t) was significantly increased during CO2 breathing while the slow phase was unchanged by the presence of CO2. The P degree fast/P degree max ratio was of the same size before and during CO2 inhalation. Inhalation of CO2 did not influence inspiratory (T1) and expiratory (TE) times during unoccluded breathing. A variable respiratory pattern was revealed during occlusion whilst CO2-free breathing: T degree max was longer than (T1) in nine cases and shorter in two. A more uniform response in ventilatory timing was found at CO2 loaded ventilation and T degree max as well as the total duration of the ventilatory cycle (T degree tot) were significantly longer than (T1) (P less than 0.01) and (Ttot) (P less than 0.05) respectively. The V1/T1 ratio was increased by 66% during CO2 provocation during unoccluded breathing. The net effect of increased inspiratory drive during CO2 breathing resulted in a VT which on average was increased by 67% (P less than 0.001) so that the mean value of E'CO2 only rose by 0.98% (P less than 0.01) from 5.18% before to 6.16% during CO2 breathing. It was concluded that ventilatory compensation to CO2 was adequate, indicating preserved respiratory centre activity. Respiratory timing, however, was unaffected by CO2 indicating a discrepancy between the effects of halothane on respiratory motor centre activity and the bulbopontine pacemaker in these young infants. PMID- 3109893 TI - Randomized clinical investigation of Ro 15-1788, a benzodiazepine antagonist, in reversing the central effects of flunitrazepam. AB - In a double-blind, randomized study the efficacy of Ro 15-1788 as a benzodiazepine antagonist was evaluated in patients anaesthetized with flunitrazepam. The effects were compared with a comparable group of patients who did not receive the antagonist. Ro 15-1788 significantly reversed the sedative and hypnotic effects of flunitrazepam and reduced the degree of anterograde amnesia. No side-effects were attributable to the drug. PMID- 3109894 TI - Effects of a heat and moisture exchanger on carbon dioxide equilibrium during mechanical ventilation with the Bain circuit. AB - The introduction of a heat and moisture exchanger (HME) into the anaesthetic circuit may cause a rise in carbon dioxide (CO2) tension through an increase in dead space. We studied the effects of the Ultipor Pall BB50 filter included 'in series' in the Bain circuit on CO2 equilibrium. Arterial carbon dioxide tension (PaCO2) was measured in 81 patients scheduled for elective surgery before and after the insertion of the filter. Results showed that: females were always more hyperventilated than males when fresh gas flow was set at 70 ml kg-1 ideal body weight; the inclusion of the filter increased the PaCO2 in the group as a whole (the difference was statistically, but not clinically, significant); PaCO2 increased after the application of the filter only in females; the effects of the filter were completely independent of the patient's age. It is concluded that the use of the Ultipor Pall BB50 filter is a safe procedure during mechanical ventilation with the Bain breathing system and there is no need to modify ventilation. PMID- 3109895 TI - In vitro activity of the new 4-quinolone compound Ro 23-6240. AB - The in vitro activity of the new 4-quinolone Ro 23-6240 was compared with that of pefloxacin, ciprofloxacin, norfloxacin, nalidixic acid and gentamicin against a total of 397 recent clinical isolates. An agar dilution procedure was used to determine MICs and two inocula (10(4) and 10(6) CFU) were used throughout. Ro 23 6240 inhibited most species of the Enterobacteriaceae, Haemophilus influenzae and Staphylococcus aureus (including methicillin-resistant strains) at less than or equal to 1 mg/l. Pseudomonas aeruginosa was somewhat more resistant (MIC 90 4 mg/l) and the Bacteroides fragilis group were considerably more resistant (MIC 90 32 mg/l). Overall Ro 23-6240 was as active as pefloxacin but was two- to eight fold less active than ciprofloxacin against most species tested. PMID- 3109896 TI - Effect of Ro 23-6240 on sensitive and resistant intracellular mycobacteria. AB - The activity of Ro 23-6240 and rifampicin against intracellular Mycobacterium fortuitum and Mycobacterium chelonei was assessed in vitro over a 48-hour period. Both agents, at an extracellular concentration of 2.0 mg/l (Ro 23-6240) and 1.0 mg/l (rifampicin), produced a significant intracellular killing of the sensitive Mycobacterium fortuitum at both 20 and 48 hours. However, neither agent was effective against the resistant Mycobacterium chelonei. It was concluded that Ro 23-6240 has a direct antimicrobial effect against sensitive intracellular mycobacteria. PMID- 3109897 TI - In vitro activity of RO 15-8074 and RO 19-5247. AB - The in vitro activity of RO 15-8074 (cefetamet) and RO 19-5247, new oral cephalosporins, was compared with that of amoxicillin, cephalexin, cefaclor, cefuroxime and erythromycin against 292 clinical isolates using the agar dilution method. Both RO 15-8074 and RO 19-5247 were very active against Proteus mirabilis, Neisseria gonorrhoeae, Haemophilus influenzae and Streptococcus pyogenes, but less active against Staphylococcus saprophyticus and Enterobacter cloacae. RO 19-5247 was more active than RO 15-8074 against Haemophilus influenzae and Streptococcus viridans. PMID- 3109898 TI - The Fritz-Lipmann lecture. DNA repair in human cells. Biochemistry of the hereditary diseases Fanconi's anaemia and Cockayne syndrome. PMID- 3109899 TI - D-galactofuranose in the N-linked sugar chain of a glycopeptide from Ascobolus furfuraceus. AB - Two types of linkages between the carbohydrate and the peptide moiety in the glycopeptide from Ascobolus furfuraceus are described. Treatment with mild alkali produced beta-elimination of a small oligosaccharide. Evidence for the O glycosidic linkage was provided by increase in absorbance at 240 nm, decrease in threonine and serine content after the alkaline treatment and detection of tritiated oligosaccharide following alkaline NaB3H4 reduction. Mannose is the sugar involved in the O-glycosidic linkage. The remaining glycopeptide was branched by galactofuranose units, which were selectivity released by mild acid hydrolysis. The N-glycosidic linkage of the sugar chain was conclusively proved by cleavage with endo-beta-N-acetyl-glucosaminidase. Sequential NaB3H4 reduction and acid hydrolysis gave [3H]glucosaminitol. The structure of the sugar chain was studied by 13C NMR spectroscopy and by methylation analysis. PMID- 3109900 TI - Purification and characterization of a beta-glucosidase from Trichoderma reesei. AB - A beta-glucosidase has been purified from culture filtrates of the fungus Trichoderma reesei QM9414 grown on microcrystalline cellulose. The beta glucosidase was purified using two successive DEAE-Sephadex anion-exchange chromatography steps, followed by SP-Sephadex cation-exchange chromatography and concanavalin-A--agarose chromatography. Evidence for homogeneity is provided by polyacrylamide disc gel electrophoretic patterns, which show a single protein band. Sedimentation equilibrium analysis yielded a molecular mass of 74.6 +/- 2.4 kDa. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis yielded a single protein band with a molecular mass of 81.6 kDa. Thus, the enzyme appears to be a single, monomeric polypeptide. The beta-glucosidase is isoelectric at pH 8.5. The enzyme is rich in basic amino acids and contains few half-cystine and methionine residues. The purified beta-glucosidase contains less than 1% by weight of neutral carbohydrate. The beta-glucosidase catalyzes the hydrolysis of cellobiose, p-nitrophenyl beta-D-glucopyranoside and 4-methylumbelliferyl beta-D glucopyranoside; the values of V/Km for each substrate were determined to be 2.3 X 10(4), 6.9 X 10(5) and 2.9 X 10(6) M-1 S-1 respectively. The enzyme is optimally active from pH 4.5 to 5.0 and is labile at higher hydrogen ion concentrations. The beta-glucosidase has an unusually high affinity for D-glucose (Ki = 700 microM). Comparison of inhibition constants for cello-oligosaccharides suggests that the substrate-binding region of the beta-glucosidase comprises multiple subsites. PMID- 3109901 TI - Beta-glucosidase from Trichoderma reesei. Substrate-binding region and mode of action on [1-3H]cello-oligosaccharides. AB - To determine the mode of action of the beta-glucosidase from Trichoderma reesei a method was developed for synthesizing [1-3H]cello-oligosaccharides with specific radioactivities of approximately 3000 Ci/mol. The beta-glucosidase removed glucosyl residues from the non-reducing end of the [1-3H]cello-oligosaccharides in a multiple attack mode with little tendency to attack the substrates repetitively. Values of Km were lower for longer cello-oligosaccharides, whereas values of V remained essentially constant. A subsite map, constructed using values of V/Km for the cello-oligosaccharides, showed that the substrate-binding region comprises primarily three subsites. PMID- 3109902 TI - Possible involvement of eicosanoids in the zymosan and arachidonic-acid-induced oxygen uptake, glycogenolysis and Ca2+ mobilization in the perfused rat liver. AB - Exposure of perfused rat livers to zymosan, arachidonic acid and phenylephrine, but not to latex particles, induces pronounced oxygen uptake, glycogenolysis and Ca2+ mobilization. The oxygen uptake induced by arachidonic acid and by zymosan remains elevated even after the agents have been removed. NaN3 was found to be much more effective in inhibiting the oxygen uptake induced by phenylephrine than that induced by zymosan or arachidonic acid. Glucose release induced by zymosan and by arachidonic acid reaches a maximum after about 2 min and then declines very rapidly even while the agents are still being infused. In contrast, glucose release induced by phenylephrine remains elevated for the duration of the infusion. Ca2+ fluxes induced by arachidonic acid are similar to those induced by phenylephrine in that efflux occurs when the agent is administered and influx occurs only when the agent is removed. This contrasts to the Ca2+ flux changes induced by zymosan where both Ca2+ efflux and Ca2+ influx occur even while zymosan is still being infused. Glucose release induced by zymosan is inhibited by bromophenacylbromide and nordihydroguaiaretic acid, but not by indomethacin. Indomethacin, however inhibits the arachidonic-acid-induced glucose release which is also inhibited by nordihydroguaiaretic acid but not by bromophenacylbromide. Indomethacin inhibits also the arachidonic-acid-induced Ca2+ flux changes whereas the zymosan- and the phenylephrine-induced Ca2+ flux changes are not inhibited by the cyclooxygenase inhibitor. The data presented in this paper suggest that in the perfused rat liver the zymosan-induced glycogenolysis, as well as the Ca2+ flux changes and glycogenolysis induced by arachidonic acid, are mediated by eicosanoids. PMID- 3109903 TI - Nitrate starvation induces homeoviscous regulation of lipids in the cell envelope of the blue-green alga, Anacystis nidulans. AB - Replacement of the normal culture liquid to a nitrate-free medium resulted in an immediate drop in the ratio of protein to lipid in isolated cell envelopes of Anacystis nidulans cells. The relative fluidity of the envelope membranes or liposomes, made from the extracted lipids of the envelope, was estimated by measuring the steady-state fluorescence polarization of 1,6-diphenyl-1,3,5 hexatriene. A thermotrophic phase transition of lipids within the cytoplasmic membrane of intact cells was also revealed by detecting the temperature-dependent absorption changes in the proportion of zeaxanthin at 390 nm. It became evident that a decrease in the proportion of protein to lipid within the cell envelope was accompanied neither by changes in the microviscosity level, nor by shifting of characteristic temperatures of the liquid-crystalline-to-gel transition of lipids. In parallel with nitrate starvation, however, the proportion of saturated fatty acids of the envelope lipids increased markedly. Accumulation of saturated, longer-chain (C18) fatty acids at the cost of C16 counterparts upon nitrate deprivation occurred in all of the complex lipids. In accordance with these findings, a pronounced decrease in the fluidity was demonstrated for the liposomes prepared from the envelope polar lipids of nitrate-starved cells compared with the corresponding control, throughout the temperature range (45-5 degrees C) studied. We propose that the fluidizing effect due to a fall in the ratio of protein to lipid was compensated by a rapidly triggering regulatory process which enables the preservation of the fluidity characteristics at an optimal level within the cell envelope of A. nidulans. PMID- 3109904 TI - Activation mechanism of monkey and porcine pepsinogens A. One-step and stepwise activation pathways and their relation to intramolecular and intermolecular reactions. AB - The activation of Sepharose-bound monkey pepsinogen A under acidic conditions proceeded by cleavage of the Leu47-Ile48 bond, indicating the occurrence of the intramolecular one-step activation, although the rate of cleavage was very slow. On the other hand the activation of monkey pepsinogen A in solution was highly dependent on pepsinogen concentration and the addition of exogenous pepsin A accelerated the rate of activation, indicating the predominance of intermolecular reaction. The cleavage site, however, was also restricted to the Leu47-Ile48 bond. Thus, apparently exclusive one-step activation occurred in monkey pepsinogen. The activation of porcine pepsinogen A in solution was also dependent on pepsinogen concentration and the addition of exogenous pepsin A accelerated the rate of activation. The major cleavage site by the exogenously added pepsin was the Leu44-Ile45 bond. Therefore the site most susceptible to the intermolecular attacks was the bond connecting the activation segment and the pepsin moiety in both monkey and porcine pepsinogens. In porcine pepsinogen, however, a part of the zymogen was activated through the intermediate form, and an intramolecular reaction was suggested to be involved in the generation of this form. These results showed that in both pepsinogens A the intramolecular reaction occurred, first yielding pepsin A or the intermediate form, which then acted intermolecularly on the remaining pepsinogen or the intermediate form to complete the activation in a short time. A molecular mechanism for the activation reaction was proposed to explain consistently the experimental results. PMID- 3109905 TI - Protein synthesis in Drosophila melanogaster embryos. Two mechanisms for guanine nucleotide exchange on eukaryotic initiation factor 2. AB - The mechanism for guanine nucleotide exchange with eukaryotic initiation factor-2 (eIF-2) from Drosophila melanogaster embryos was studied using the reaction eIF-2 X [3H]GDP + GDP (GTP) in equilibrium eIF-2 X GDP (GTP) + [3H]GDP. When highly purified eIF-2 is used the rate of nucleotide exchange is greatly reduced by Mg2+ and this reduction is overcome by the guanine-nucleotide-exchange factor (GEF) of rabbit reticulocytes. This GEF-dependent exchange is inhibited when Drosophila eIF-2 is either phosphorylated by the hemin-controlled inhibitor (HCI) of rabbit reticulocytes or treated with phosphatidylserine or a rabbit eIF-2 X phosphatidylserine complex. The Mg2+ impairment of guanine nucleotide exchange is less severe when highly purified eIF-2 is incubated at a higher temperature (37 degrees C) and is not observed at any temperature if partially purified eIF-2 is used instead of the highly purified factor. In the latter two cases the exchange is not inhibited by either phosphorylation with HCI or phospholipid treatment of Drosophila eIF-2, possibly suggesting that the observed exchange is not mediated by a GEF-like factor. Our data support two possible mechanisms for GDP/GTP exchange with Drosophila embryos eIF-2: a GEF-dependent exchange, similar to that described in rabbit reticulocytes, which may be regulated by phosphorylation of eIF-2, and a factor-independent exchange which appears to be insensitive to this type of control. PMID- 3109906 TI - Evidence for a type-IV-related collagen in Drosophila melanogaster. Evolutionary constancy of the carboxyl-terminal noncollagenous domain. AB - Type IV collagen, a major structural component of basement membrane, has been characterized only in vertebrates. It is unique among the collagenous proteins in that it forms specific lattice networks by end-to-end interactions. In particular, in mammals the C-terminal noncollagenous domain (NCl) of collagen IV was shown to be one of the major cross-linking sites in the network assembly. Here, we give the first direct evidence of type-IV-related collagen in invertebrates by sequence analysis of cDNA and genomic DNA clones for the 3'-end of a previously characterized Drosophila collagen gene. The data describe the C terminal 190 amino acid residues of the triple helix and the entire noncollagenous domain (231 amino acids) of the chain encoded for by this gene. Comparison with data reported for human and mouse alpha 1(IV) chains reveals that triple-helix regions are quite different, while NC1 structures are very similar. This suggests different constraints on triple-helix and NC1 domains during evolution. Present data support the assumption that the NC1 structure originated from duplication of an ancestral sequence; the extent of both interspecies and intramolecular homologies suggests the maintenance in vertebrates and invertebrates of an ancestral specific function. PMID- 3109907 TI - Molecular cloning and sequencing of a cDNA encoding the acyl carrier protein and its flanking domains in the mammalian fatty acid synthetase. AB - Cloned cDNAs containing coding sequences for domains proximal to the carboxy terminus of the rat fatty acid synthetase have been isolated using an expression vector and domain-specific antibodies. The coding regions were assigned to specific domains of the multifunctional complex by identification of sequences coding for characterized peptide fragments and by recognition of sequences homologous to other monofunctional enzymes. Two clones contain the entire coding region for the acyl carrier protein domain. The sequence is flanked at the 3'-end by a region coding for the thioesterase domain and at the 5'-end by a sequence coding for a reductase, most likely the ketoreductase domain. Thus the ordering of these domain-coding regions in the fatty acid synthetase mRNA is established. The acyl carrier protein domain exhibits about 25% homology with that of the discrete monofunctional acyl carrier proteins of Escherichia coli, spinach and barley, the ketoreductase domain exhibits about 25% homology with bacterial dihydrofolate reductases and the active site of the thioesterase domain exhibits both primary and secondary structural features common to the serine proteases. These findings lend support to the hypothesis that the polyfunctional fatty acid synthetase probably arose by a complex evolutionary process involving fusion of genes coding for seven individual enzymes. PMID- 3109908 TI - Tissue form of type VII collagen from human skin and dermal fibroblasts in culture. AB - The triple-helical domain of type VII collagen was isolated from human placental membranes by mild digestion with pepsin, and polyclonal antibodies were raised in rabbits against this protein. After affinity purification the antibodies specifically recognized type VII collagen in both the triple-helical and the unfolded state. They also reacted with the fragments P1 and P2, derived from the triple-helical domain by further proteolysis with pepsin, but did not crossreact with other biochemical components of the dermal connective tissue. In skin the presence of a fragment of type VII collagen, similar to that isolated from placenta, was demonstrated by SDS-PAGE and immunoblotting. Type VII collagen represented less than 0.001% of the total collagen extracted by pepsin digestion from newborn or adult skin. The tissue form of type VII collagen was obtained from dermis after artificial epidermolysis with strongly denaturing buffers under conditions reducing disulfide bonds. The protein was identified by immunoblotting with the antibodies. The molecule was composed of three polypeptides with an apparent molecular mass of about 250 kDa, each. Similar large-molecular-mass chains could be identified by immunoblotting in extracts of human fibroblasts in culture. PMID- 3109909 TI - Specific processing of the thyrotropin-releasing prohormone in rat brain and spinal cord. AB - Thyrotropin-releasing hormone (TRH) and TRH extended peptides were extracted from rat hypothalamus and spinal cord and resolved by gel exclusion chromatography under dissociating conditions. Peptides related to TRH were detected by trypsin digestion and radioimmunoassay with an antibody to TRH or an antibody raised against the pentapeptide Glp-His-Pro-Gly-Lys. In addition to the tripeptide hormone a series of C-terminally extended forms of TRH was shown to occur in both tissues; no N-terminally extended peptides were detected. The structure of the TRH-related peptides was confirmed by chromatographic identification of the N terminal pentapeptide sequence released by trypsin. The TRH extended peptides, which accounted for 15-20% of the total TRH, were present in three groups of different molecular size corresponding to predicted fragments of the TRH prohormone. One of the peptides in the spinal cord was identified by chromatographic comparison with a synthetic 16-residue peptide representing residues 154-169 of the prohormone. In the spinal cord the TRH extended peptides differed in their relative concentrations from the corresponding peptides in the hypothalamus, possibly reflecting differences in processing. The finding of extended forms of TRH in which the extension occurs only on the C-terminal side of the hormone sequence shows that the prohormone undergoes highly specific processing. PMID- 3109910 TI - Laminin-nidogen complex. Extraction with chelating agents and structural characterization. AB - Large quantities of intact laminin-nidogen complex could be extracted from a mouse tumor basement membrane with a physiological buffer containing EDTA. Analysis of the purified complex demonstrated that the two proteins occur in an equimolar ratio and that anchoring of these complexes to the extracellular matrix requires divalent cations. Reversible dissociation of the complex was achieved with 2 M guanidine X HCl and has been used for purification of the individual components. Electron microscopy and binding studies using laminin fragments demonstrated that nidogen interacts specifically with the center of the cross shaped laminin molecule as represented by the short-arm structure fragment 1. The complex was also useful to confirm and refine a previously proposed dumb-bell structure of nidogen and to prepare and characterize the cell-binding fragment 8 from the long arm of laminin. PMID- 3109911 TI - Primary and quaternary structure of the catabolic ornithine carbamoyltransferase from Pseudomonas aeruginosa. Extensive sequence homology with the anabolic ornithine carbamoyltransferases of Escherichia coli. AB - We have determined the complete nucleotide sequence of the arcB gene from Pseudomonas aeruginosa strain PAO and we have purified the arcB product, the catabolic ornithine carbamoyltransferase (EC 2.1.3.3), to apparent homogeneity from the same strain. The N-terminal amino acid sequence, the total amino acid composition and the subunit size of the purified enzyme were in agreement with nucleotide sequencing results, which predict a polypeptide of 336 amino acids (Mr 38,108). Crosslinking experiments suggest that the native enzyme (apparent Mr approx. 420,000) basically consists of a trimer aggregating to form nonamers or dodecamers. The arcB gene of P. aeruginosa had strong homology with the argF and argI genes which code for the anabolic ornithine carbamoyltransferase isoenzymes in Escherichia coli; 63% of the nucleotides and 57% of the amino acids were absolutely conserved in arcB and argF. This indicates a close evolutionary relationship between these genes although their products have different physiological functions in the cell. Under conditions of induction (energy depletion) the catabolic ornithine carbamoyltransferase represented greater than or equal to 10% of the total cellular protein. Like other highly expressed Pseudomonas genes, the arcB gene was found not to use seven codons which correspond to minor or weakly interacting tRNA species in E. coli. PMID- 3109912 TI - Molecular cloning of a pea H1 histone cDNA. AB - A pea (Pisum sativum, var. Little Marvel) H1 histone cDNA has been isolated from a lambda gt11 expression vector library. This cDNA has been sequenced and shown to represent the entire protein-coding region of the mRNA. The deduced protein sequence is 265 amino acids long (28018 Da) and contains 70 lysines and 3 arginines. The structure of the encoded protein is comparable to animal lysine rich histones. The central region, which has an amino acid composition similar to that found in the globular domains of animal lysine-rich histones, is flanked by an amino-terminal region rich in lysine, glutamic acid and proline and by a carboxyl-terminal region rich in lysine, alanine, valine and proline. Despite the structural similarities, the protein has little sequence homology with animal lysine-rich histones. This H1 protein is unusual because 12 of the first 40 amino acids are glutamic acid. PMID- 3109913 TI - Structural characterization of human interferon gamma. Heterogeneity of the carboxyl terminus. AB - Natural human interferon gamma(IFN-gamma) was purified from the conditioned medium of peripheral blood leukocytes using selective silica gel adsorption and antibody-affinity chromatography. SDS-PAGE and Western blot analysis demonstrated three major species with molecular masses of 25 kDa, 20 kDa and 17 kDa. Structural analysis of this natural IFN-gamma preparation demonstrated a pyroglutamate residue at the amino terminus and a heterogeneous carboxyl terminus. The longest and most predominant polypeptide was 138 amino acids in length, which is five residues shorter than the sequence predicted from the cDNA. The presence of multiple-carboxyl-terminal forms indicated possible proteolytic processing during induction or protein purification. Limited proteolytic digestion of full-length recombinant IFN-gamma with endoproteinase Lys-C and trypsin revealed that the carboxyl-terminal 15 residues could be released under conditions in which the core portion of the polypeptide chain remained intact. Thus, the heterogeneity of natural IFN-gamma may be explained by partial proteolytic degradation of the molecule and differences in the degree of glycosylation as previously reported [Rinderknecht, E., O'Conner, B. H. & Rodriguez, H. (1984) J. Biol. Chem. 259, 6790-6797]. PMID- 3109914 TI - Factor VIII binds to von Willebrand factor via its Mr-80,000 light chain. AB - The formation of a complex between factor VIII (FVIII) and von Willebrand factor (vWF) was studied using purified radiolabeled human FVIII and purified human vWF. A binding assay was developed in which vWF was coated on microtiter wells. FVIII was shown to bind specifically and reversibly to the immobilized vWF. At a coating of 70 pg vWF/well, binding was half-maximal at a FVIII concentration of 70 +/- 10 pM. In order to ascertain which part of FVIII interacted with vWF, eight monoclonal antibodies, directed against FVIII, were tested for their ability to inhibit FVIII-vWF interaction. One of the eight antibodies, CLB CAg:58, inhibited binding completely. This antibody was demonstrated to react with the Mr-80,000 light chain of FVIII. Direct evidence for the involvement of this chain in vWF binding was obtained by studying the binding of isolated, radiolabeled FVIII heavy and light chains. In a typical experiment 23-30% of the radioactivity bound when the FVIII light chain was added and less than 1% when the FVIII heavy chain was added. PMID- 3109915 TI - Whole body retention of 99mTc-diphosphonate. Relation to biochemical indices of bone turnover and to total body calcium. AB - Whole body retention (WBR) and urinary excretion (UE) of 99mTc-diphosphonate were determined in 161 healthy adults and the results were compared to accepted biochemical markers of bone turnover. WBR was corrected for total body bone mineral (TBBM) and UE for forearm bone mineral content (BMC). Both uncorrected and corrected retention measurements were highly significantly correlated to the biochemical markers (P less than 0.001), but the r values were low (0.22-0.64). All bone turnover variables demonstrated considerably higher levels of bone turnover in postmenopausal women than in premenopausal women (P less than 0.001), whereas the variables were unchanged with age in men. The correction of WBR for TBBM and UE for BMC increased the validity of the retention methods and the two calculations gave exactly the same results on a group basis, both demonstrating significantly higher bone turnover in women than in men in each age group (P less than 0.05-P less than 0.001). All the turnover variables were measured in a group of perimenopausal women (n = 33). The data clearly demonstrated that bone turnover is menopause dependent, whereas age in itself is of minor significance. PMID- 3109916 TI - A trial of semiquantitative analysis of whole body bone scintigraphy in renal osteodystrophy. AB - Four color processed whole body bone scintigraphy with 99mTc-methylene diphosphonate was performed in six patients on maintenance hemodialysis, and the results of semiquantitative colorimetric analysis were compared with those of a normal group. The difference between the two (control and patient group) was statistically significant (P less than 0.01). Furthermore, the effect of 1 alpha hydroxyvitamin D3 treatment on renal osteodystrophy was evaluated by this method. The results indicated that this method provides a useful method for assessing the response of renal osteodystrophy to treatment. Two representative cases of renal osteodystrophy are presented to illustrate the usefulness of this approach to semiquantitative whole body bone scanning. PMID- 3109917 TI - 89Sr radionuclide therapy: dosimetry and haematological toxicity in two patients with metastasising prostatic carcinoma. AB - We present dosimetry for spinal metastases and red bone marrow in two patients who received 89Sr therapy for disseminated prostatic carcinoma. Absorbed dose to metastases was estimated by combining 85Sr gamma camera studies with computed tomographic measurements of bone mass, and doses of 20 cGy/MBq and 24 cGy/MBq were found for vertebral metastases that uniformly involved the bodies of L3 and D12 respectively. Absorbed dose to red bone marrow was estimated from total body strontium retention studies using the ICRP model for bone dosimetry, and a ratio of metastatic to marrow dose of around 10 was found in each patient. Although they received comparable treatment activities of around 200 MBq, the patients showed markedly different haematological response, this difference being confirmed when each received a second 89Sr treatment 6 months after the first. As a result, clinically significant thrombocytopenia occurred in one patient which prevented further radiostrontium therapy being given. PMID- 3109918 TI - 111In-tropolonate labelled platelets; studies in normals and in patients with thrombocytopenia. AB - Human platelets were labelled with aqueous 111In-tropolonate in comparison with 111In-oxinate. In normals the labelling efficiency with 111In-tropolonate was higher (93% +/- 2%) than with 111In-oxinate (67% +/- 8%) (P less than 0.05). In cases of severe thrombocytopenia, lower labelling efficiencies were obtained. In six normals a mean platelet life of 9 days +/- 3 days and an initial recovery of 59% +/- 15% were obtained. In twelve patients with thrombocytopenia the mean platelet life was 4 days +/- 4 days and the initial recovery was 58% +/- 20%. The absolute uptake of radioactivity in spleen and in liver in both groups are reported. PMID- 3109919 TI - The effect of treatment with an LH-RH agonist (Buserelin) on gonadal activity growth and bone maturation in children with central precocious puberty. AB - Twenty-five children (23 girls and 2 boys) with central precocious puberty were treated with the LH-RH agonist D-Ser (TBU)6-LHRH (1-9) EA (HOE 766, Buserelin) by daily subcutaneous injection for a period of 11-18 months. Eight girls and 2 boys previously treated with cyproterone acetate (CPA, 100-150 mg/m2 body surface per day) and the first seven newly diagnosed patients received 2 X 10 micrograms Buserelin/kg bodyweight per day for 1 week, followed by a maintenance therapy of 1 X 10 micrograms/kg per day. After an initial marked increase, oestrogen (E2) serum levels in girls and testosterone (T) values in boys decreased. After a treatment period of 6-20 weeks the patients received 2 X 20 micrograms Buserelin/kg per day for 1 week and thereafter a maintenance dosage of 20 micrograms/kg per day to obtain full suppression (i.e. E2 less than 50 pmol/l; T less than 1 nmol/l). The remaining eight patients started directly on 2 X 20 micrograms Buserelin/kg per day followed by 1 X 20 micrograms/kg per day. All eight girls with menarche before therapy had no further menses. In all girls there was a reduction of palpable breast tissue. Decrease of pubic hair development was observed in 3 girls, an increase was seen in 5 girls, whereas in the remaining 15 girls no change was observed. Both boys had a reduction of testicular volume and of pubic hair.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3109920 TI - Interferon gamma regulates HLA-D expression on solid tumors in vivo. AB - In vivo administration of recombinant human interferon-gamma, rIFN-gamma, to nude mice bearing human tumor xenografts resulted in a strong induction of HLA-DR expression on the tumor cells in 2 of 3 lines tested. The induction was dose dependent and declined rapidly after cessation of therapy. IFN-gamma also switched on DQ and DP products when the xenograft cells were treated in vitro. The in vivo alteration of tumor surface properties by rIFN-gamma may have therapeutic implications. PMID- 3109921 TI - The ATP assay is more sensitive than the succinate dehydrogenase inhibition test for predicting cell viability. AB - The succinate dehydrogenase inhibition (SDI) test and the adenosine triphosphate (ATP) assay, are both used for in vitro human tumor chemosensitivity testing. We exposed HeLa cells to various concentrations of mitomycin C for 1, 2 or 3 days and found that the decrease in number of viable cells correlated with that of succinate dehydrogenase (EC 1.3.99.1) activity and that of intracellular ATP level of the viable cells. In the dead cells, the ATP level was extensively decreased, but the succinate dehydrogenase activity remained at a level of 24% of that of mitomycin C-untreated viable cells, even on day 3. Thus, the ATP level better reflected the cell viability. In clinical situations, the succinate dehydrogenase activity and the ATP level are assayed in whole cells following exposure to anticancer drugs, therefore the activity remaining in the dead cells must be taken into consideration for the chemosensitive prediction with the SDI test, but not with the ATP assay. This higher sensitivity of the ATP assay will enable a more accurate prediction of cell viability. PMID- 3109922 TI - A programmed functional and phenotypic development of bone marrow-derived cytotoxic cell precursors in vitro. AB - An analysis of function and marker expression during cytotoxic cell differentiation in vitro from T cell-depleted bone marrow precursors is described. Cytotoxic activity is not detectable during the first five days of culture, but rises abruptly soon after. Antibody plus complement depletion studies show that cytotoxic cells derive from Thy-1-negative precursors and undergo a continual increase in Thy-1 and Lyt-2 marker expression as the culture progresses. A reciprocal decrease in asialo-GM1 antigen expression on effector cells is seen. The J11d-negative precursor cells acquire J11d (an antigen known to mark cortical thymocytes) at an intermediate stage of culture, but revert to the J11d-negative phenotype prior to functional acquisition. At least some effectors are T cell receptor positive as illustrated by an anti-T cell receptor antibody-mediated killing assay. These patterns precisely correlate with those detected among developing T cells in vivo. Results may indicate that a programmed course of differentiation inherent to bone marrow cells may be triggered in the absence of a thymic environment. PMID- 3109923 TI - Interleukin 2 receptor traffic in a murine cytolytic T cell line. AB - We have analyzed different parameters of the interleukin 2 receptor (IL2R) traffic in a murine IL2-dependent T cell line, B6.1. These cells express about 10(5) IL2R, of which approximately 10% are of high affinity (HAR). About 90% of all mature immunoprecipitable receptor molecules in the cell are on the cell surface. Measurements of the half life and of the rate of receptor synthesis indicate that these cells produce approximately 500 receptor molecules per cell and min. IL2 deprival for less than 6 h does not affect this rate. B6.1 cells internalize IL2 via their HAR only, with a maximal rate of about 500 molecules per cell and min. Among the receptors present at a given time on the cell surface, about 15% are internalized within 30 min. Receptor internalization is independent of IL2. The data obtained argue against rapid recycling of the HAR. The rate of receptor synthesis can be reconciled with the rate of IL2 internalization and the observation that internalization occurs only via HAR by assuming that cell surface low-affinity receptors can be transformed into HAR by associating with other molecules. PMID- 3109924 TI - B cell differentiation and interleukin 2 (IL2): corticosteroids interact with monocytes to enhance the effect of IL2. AB - Upon in vitro activation by Staphylococcus aureus Cowan I strain (SAC) human peripheral blood B cells produce only marginal amounts of Ig when cultured in the presence of interleukin 2 (IL2; 10 U/ml). This response is only moderately increased by the addition of monocytes or of IL1. In the presence of dexamethasone (DM; 10(-7)-10(-8) M) microgram amounts of both IgM and IgG are produced in co-cultures of B cells and monocytes. This response is not modified by inhibitors of cyclooxygenase and is specifically inhibited by a monoclonal antibody interfering with the binding of IL2 to its receptor. This enhancing effect of DM is not observed in the absence of monocytes even if IL1 is added to the cultures. Moreover, monocytes pretreated with DM stimulate the response of B cells cultures in the absence of DM. Enhancement of Ig production by DM and monocytes could be demonstrated with B cells obtained from a patient suffering from a hyperlymphocytic form of B cell type chronic lymphocytic leukemia, and in this case only IgM was produced. Importantly, DM fully inhibited the IL2 dependent proliferation of these monoclonal B cells. Thus, physiological concentrations of DM can modulate monocytic function to enhance the differentiative effect of IL2. PMID- 3109925 TI - Noradrenergic mechanisms in gamma-hydroxybutyrate-induced seizure activity. AB - The electroencephalographic (EEG) response of 6-hydroxydopamine (6-OHDA)-treated and control rats to gamma-butyrolactone (GBL) the prodrug of gamma hydroxybutyrate (GHB), was determined. Neonatal treatment with 6-OHDA produced a significant reduction of noradrenaline in cortex and hippocampus while sparing noradrenaline in the hypothalamus. Brain dopamine was unaffected. The electrographic seizure produced by GBL was significantly prolonged and more severe in the 6-OHDA-treated animals. That portion of the hypersynchronous seizure induced by GBL which is pharmacologically sensitive to antipetit mal anticonvulsants, Stage 1, was however shortened in the 6-OHDA-treated animals. Reduction of forebrain noradrenaline seems to have a complex effect on GBL induced seizure in that it results in a reduction of hypersynchronous EEG activity but in a prolongation of the more severe EEG changes of burst suppression normally seen with higher doses of GBL. PMID- 3109926 TI - Ro 15-1788 both antagonizes and potentiates adenosine-evoked depression of cerebral cortical neurons. AB - The effects of Ro 15-1788, a benzodiazepine antagonist with some agonist properties, were studied on adenosine and adenosine 5'-N-ethyl-carboxamide (NECA) evoked depressions of rat cerebral cortical neuronal activity. Iontophoretically applied Ro 15-1788 had both antagonistic and potentiative interactions with adenosine. Reductions in the magnitude of adenosine-evoked depressions of firing were evident during the period of Ro 15-1788 application, with a long-lasting potentiative effect becoming apparent upon termination of the Ro 15-1788 application. Depressions of cell firing evoked by NECA, an uptake-resistant analog of adenosine, were antagonized by Ro 15-1788, with no subsequent potentiation. Larger applications of Ro 15-1788 had a depressant action on neuronal firing, which was antagonized by caffeine (20 mg/kg), an adenosine receptor blocker. These results indicate that Ro 15-1788 may be an antagonist at the adenosine receptor as well as a potentiator of the adenosine response. The prolongation of the adenosine depression is likely to be the result of a persistent inhibition of adenosine uptake by Ro 15-1788. These diverse effects on the adenosine response may account for some of the complex behavioral actions of Ro 15-1788. PMID- 3109927 TI - Influence of microinjection of glucagon into ventromedial hypothalamus on acetate metabolism in liver slices of rabbit. AB - Glucagon was injected directly into the ventromedial hypothalamic nuclei (VMH) of rabbits, and changes in hepatic acetate metabolism were studied. The injection of 3 ng glucagon into the VMH of intact rabbits increased the rates of 14C transfer from 14C-1-acetate into CO2, glucose and ketone bodies but decreased those into cholesterol ester, triglyceride, free cholesterol, free fatty acids and phospholipids. However, after glucagon injection into the VMH of rabbits with VMH lesions and the parietal cortex of intact rabbits, hepatic acetate metabolism did not differ from that of the control rabbits, which received saline injection into the same brain regions. These observations support the hypothesis that the VMH are parts of a glucagon-sensitive brain regulator system in the hepatic acetate metabolism. PMID- 3109928 TI - Effects of hysterectomy and uterine extracts on the gonadotrophic hormones and the weight of endocrine organs of female rats. AB - The previous observation that hysterectomy of rats results in increased pituitary nucleic acid turnover was followed up by studies on pituitary function in hysterectomized adult female rats with or without treatment with charcoal-treated crude uterine aqueous extracts. Hysterectomy had no effect on the pituitary or plasma LH and FSH concentrations. Administration of crude uterine extracts diminished the post-castrational rise of the pituitary FSH content without affecting the plasma FSH or LH concentrations. Hysterectomy decreased body weight but increased adrenal weight of ovariectomized animals. However, the body weight and pituitary weight of both the intact and ovariectomized animals increased significantly following 14 days of treatment with uterine extracts. The ovarian weight of the intact rats was reduced by this treatment. The pituitary nucleic acid content of castrated but oestradiol-substituted rats was reduced by hysterectomy. Plasma corticosterone concentrations were not affected by the above mentioned treatments. Uterine extracts inhibited the basal and GnRH induced LH release from isolated pituitary cells in culture. The effects of hysterectomy and/or administration of crude uterine aqueous extracts show that the uterus contains biologically active, non-steroidal substances which affect pituitary function of adult female rats. PMID- 3109929 TI - The effect of recombinant human tumour necrosis factor on growth and macromolecular synthesis of human epithelial cells. AB - We have studied the effect of recombinant human tumour necrosis factor (rHuTNF) on growth and macromolecular synthesis in a range of normal and transformed epithelial cell types. Tumour necrosis factor did not affect the growth of normal human mammary epithelial cells, but its growth-inhibitory action on the SV40 transformed human mammary epithelial cell line HBL-100 increased with passage number in association with a progression of malignant phenotype. However, of two lines derived from nude mouse tumours of HBL-100 lines, one, HBLT-12, did not respond to rHuTNF, and the other, HBLT-11 showed some growth stimulation by high dose rHuTNF. Macromolecular synthesis in HBLT-11 was not affected by rHuTNF. The breast cancer cell lines MCF-7 and BT20 were sensitive to the cytotoxic effects of rHuTNF. In MCF-7 a gradual decrease in RNA and DNA synthesis occurred over 48 h, ending with an accumulation of cells in S and G2 phase of the cell cycle and cell death. The addition of alpha- or gamma-interferon increased, but did not accelerate the cytotoxicity of rHuTNF. PMID- 3109930 TI - Enzymatic characterization of peanut agglutinin-binding components in the retinal interphotoreceptor matrix. AB - Previous histochemical and biochemical studies have documented the presence of carbohydrate-containing molecules in the retinal interphotoreceptor matrix (IPM). The lectin peanut agglutinin (PNA), which preferentially binds galactose containing carbohydrates, especially galactose-galactosamine linkages, selectively labels cone photoreceptor-associated domains of the IPM ('cone matrix sheaths') in a variety of vertebrate retinas. In the studies described here, the nature of these PNA-binding components was investigated by monitoring the effects of proteolytic and glycosidic enzymes on binding of the lectin in the retina and IPM. All proteolytic enzymes tested cause a marked reduction in PNA-binding to cone matrix sheaths, suggesting that proteinaceous components are important to their organization. Exposure to O-glycanase, but not N-glycanase, markedly reduces binding of PNA to cone matrix sheaths indicating that O-linked oligosaccharides are probably responsible for its binding. Galactose oxidase treatment reduces PNA-binding throughout the retina and IPM, confirming that galactose moieties are involved in its binding. beta-Galactosidase (either before or after neuraminidase treatment) does not alter the pattern of PNA binding, suggesting that neither terminal nor penultimate beta-linked galactose residues constitute a major proportion of the lectin's binding sites in the retina. Neuraminidase treatment markedly increases the density and distribution of PNA binding throughout the retina and IPM, however, this effect appears to be, at least in part, the result of the binding of the lectin to neuraminidase molecules that become associated with tissue sections in addition to binding to carbohydrate groups unmasked by desialation. Exposure to chondroitinases causes disruption of the morphological integrity of cone matrix sheaths and slight diminution of PNA binding. Other enzymes acting on common constituents of extracellular matrices do not have similar effects. Taken together, these observations suggest that PNA-binding to cone matrix sheaths is due to the presence of glycoconjugates with galactose-containing, O-linked oligosaccharide chains. PMID- 3109931 TI - Lighting conditions affect the levels of plasma gonadotropins differently in old and young castrated male rats. AB - It has been suggested that the decreased plasma levels of FSH and LH, often found in old male rats, are due to a diminished adenohypophyseal capacity to secrete the hormones and/or by changes in the hypothalamic regulatory system. We studied the effect of varying lighting conditions (12/12 h LD, continuous light and continuous darkness) on the plasma levels of the gonadotropins in castrated young adult and old male rats. We expected the sensitivity of the regulatory system to light to decrease or disappear with aging. The results for FSH supported this hypothesis: the plasma levels of FSH were more stable to changes of lighting conditions in the old rats. In disagreement with our hypothesis, the levels of LH were more sensitive to light changes in old than in young rats. It was concluded that the regulatory systems of the two hormones vary differently with age. PMID- 3109932 TI - Relationships of the soluble human A, B, and H antigens of blood group A1B individuals. AB - Ouchterlony double diffusion reactions with precipitating antibodies and lectins provide visual evidence that in saliva of A1B secretor individuals the A and B antigens are predominantly situated on the same molecule, while the H antigen is on a different molecule. PMID- 3109933 TI - Serum concentration of N-terminal procollagen peptide of collagen type III in schistosomal liver fibrosis. AB - The major cause of mortality in human schistosomiasis is the chronic granulomatous reaction of the liver tissue to Schistosoma mansoni eggs. Liver biopsy still provides the best evaluation of the degree of liver damage. However, liver biopsy does not provide an image of the dynamic process of fibrogenesis. Variations of concentrations of procollagen type III peptide in sera have been proposed to be significant markers of liver fibrosis. Thus, liver function tests in relation to histopathological diagnosis and procollagen type III peptide concentrations were studied in patients with schistosomiasis and revealed a high correlation between the serum procollagen type III peptide and the degree of fibrosis in liver tissue. PMID- 3109934 TI - Migration of leukaemic lymphocytes (chronic lymphocytic leukaemia) through a 3-D collagen gel: a possible prognostic factor. AB - Migratory properties of malignant lymphocytes in 27 patients with chronic lymphocytic leukaemia (CLL) were investigated using 3-D collagen gel. There was significant impairment of migration in malignant lymphocytes as compared with normal lymphocytes. Moreover there was an inverse correlation between Rai's staging and the migration index. Patients with progression of disease also showed a decrease in migration index. There was no correlation between kappa and lambda type in terms of migration index. The prognostic significance of the migratory properties of malignant lymphocytes is also discussed. PMID- 3109935 TI - Blood clonal B cell excess at diagnosis in multiple myeloma: relation to prognosis. AB - 112 patients with multiple myeloma have been studied at diagnosis for the presence of blood clonal B-cell excess (CBE), defined as a ratio between kappa+ and lambda+ lymphocytes outside the normal range (0.9-3.5). 48 patients (43%) had CBE. The increase in light chain-bearing lymphocytes was always that of the M component light chain isotype. The proportions of patients exhibiting CBE were the same in different stages. The response frequency was not influenced by the presence of CBE. However, patients with CBE had a shorter remission duration time (p less than 0.001) and total survival (p less than 0.05) than those without CBE. This was also noticed when each clinical stage was analyzed separately. Moreover, survival was shorter in patients with a large fraction of CBE than in those with a small one. Cox regression analysis revealed that CBE was a much stronger predictor of remission duration than age, clinical stage and renal dysfunction. CBE and response to initial treatment independently were the best factors to indicate survival. It is suggested that analysis of CBE should be included in the clinical characterization of untreated patients with multiple myeloma. PMID- 3109936 TI - Simultaneous transient erythroblastopenia and agranulocytosis: IgG-mediated inhibition of erythrogranulopoiesis. AB - We report a case of simultaneous transient erythroblastopenia and agranulocytosis recovering spontaneously. In vitro study using autologous bone marrow cells after recovery demonstrated IgG-mediated inhibition of both erythropoiesis and granulopoiesis but not megakaryopoiesis. The inhibitory activity disappeared shortly after remission. These findings suggest that IgG-mediated inhibition of hematopoiesis may be pathogenetic for transient bone marrow failure of the patient. PMID- 3109937 TI - Success of bone marrow transplantation in congenital Diamond-Blackfan anaemia: a case report. AB - A 6-yr-old girl with congenital corticosteroid-resistant pure red cell aplasia was treated with bone marrow transplant from her HLA-identical, MLC-unreactive sister in November 1984 following conditioning with busulfan and cyclophosphamide. Full engraftment was obtained and the patient at 21 months post transplant is in excellent clinical condition maintaining normal red cell counts. We conclude that BMT should be considered as a therapy for at least the most severe cases of Diamond-Blackfan anaemia resistant to corticosteroids. Successful outcome of this therapy provides an argument for the stem cell origin of this disorder. PMID- 3109938 TI - HIV seroconversion in Swedish haemophiliacs: relation to type and dosage of factor concentrate. AB - Human immunodeficiency virus (HIV) seroconversion among 40 Swedish haemophilia A patients has been investigated by retrospective sera testing. 22/40 patients had developed HIV antibodies before 1983, i.e., when heat-treatment of American factor concentrates was introduced. All patients had received American and Swedish factor concentrates, thus no case of seroconversion was seen among patients treated exclusively with non-heat-treated Swedish concentrates. Of 79 patients with severe or moderate haemophilia, all of whom had received both American and Swedish concentrates, the 36 seropositives were compared with the 43 seronegatives. The total number of units received did not differ between the two groups, though the seropositive group had received significantly more American concentrate. Two batches of concentrate were proved to have been infected. 29 seropositive and 13 seronegative patients had been treated with at least one of these batches. As expected, and unlike most of the seronegative patients, patients in the seropositive group generally had abnormal lymphocyte subsets. PMID- 3109939 TI - Studies on 1,2,3-triazole derivatives as potential inhibitors of the cyclo oxygenase. AB - A number of novel alpha-[4-substituted-(1,2,3-triazole)]propionates have been prepared and tested as inhibitors of arachidonic acid-induced malondialdehyde formation in human platelets. The obtained products confirmed previous structure activity relationships. Some of them showed moderate inhibitory activity. PMID- 3109940 TI - 15N and 1H NMR evidence for multiple conformations of the complex of dihydrofolate reductase with its substrate, folate. AB - The binding of folate to Lactobacillus casei dihydrofolate reductase in the presence and absence of NADP+ has been studied by 15N NMR, using [5-15N]folate. In the presence of NADP+, three separate signals were observed for the single 15N atom, in agreement with our earlier evidence from 1H and 13C NMR for multiple conformations of this complex [(1982) Biochemistry 21, 5831-5838]. The 15N spectra of the binary enzyme-folate complex provide evidence for the first time that this complex also exists in at least two conformational states. This is confirmed by the observation of two separate resonances for the 7-proton of bound folate, located by two-dimensional exchange spectroscopy. PMID- 3109941 TI - Protein kinase C phosphorylates tau and induces its functional alterations. AB - We found that tau, one of the major microtubule-associated proteins, is a good substrate for protein kinase C. The phosphorylation occurred mainly on serine residues and the sites phosphorylated by protein kinase C were largely different from those phosphorylated by cAMP-dependent protein kinase as analyzed by phosphopeptide mapping. The protein kinase C-mediated phosphorylation of tau reduced its abilities to promote tubulin polymerization and to cross-link actin filaments. The reduction in its abilities was in proportion to the number of phosphates incorporated into tau. PMID- 3109942 TI - Formation of lipoxin A by granulocytes from eosinophilic donors. AB - The formation of arachidonic acid-derived lipoxygenase products was examined with human granulocytes obtained from eosinophilic donors. These eosinophil-enriched leukocyte populations, challenged in vitro with the ionophore of divalent cations A23187, transformed both exogenous and endogenous sources of arachidonic acid to several lipoxygenase-derived products, including 5(S), 6(R),15(S)-trihydroxy 7,9,13-trans-11-cis-eicosatetraenoic acid (lipoxin A). Lipoxin A was detected and characterized by high-pressure liquid chromatography (HPLC), ultraviolet absorbance, and gas-liquid chromatography-mass spectroscopy. Neither lipoxin B nor 6(S)-LXA was consistently detected in extracts from these incubations. The amounts of lipoxin A formed were proportional to the percentage of eosinophils present in the suspension. The results indicate that granulocytes from eosinophilic donors can generate lipoxin A. PMID- 3109943 TI - Interaction of the human insulin receptor with the ras oncogene product p21. AB - Autophosphorylation of the purified human insulin receptor tyrosyl kinase was found to be inhibited by the ras oncogene product p21 in a concentration- and GDP dependent manner. GDP-beta-S but not Gpp(NH)p could substitute for GDP in eliciting the ras-dependent inhibition. The inhibition was seen with both normal or mutant (Lys-61) p21N-ras and normal or mutant (Val-12) p21Ha-ras. Inhibition occurred at 23 degrees C but not 4 degrees C and was unaffected by the presence or absence of insulin although insulin stimulated the autophosphorylation rate of the receptor beta-subunit some 2-fold. The insulin receptor did not phosphorylate native p21Ha-ras in the presence or absence of added guanine nucleotide. After denaturation of p21Ha-ras with urea it became a substrate, but then failed to inhibit receptor autophosphorylation even in the presence of added GDP. PMID- 3109944 TI - Primary structure of duck amyloid protein A. The form deposited in tissues may be identical to its serum precursor. AB - The amino acid sequence has been determined for the major protein that accumulates in amyloid fibrils in tissues of the Pekin duck. With the exception of 16 residues at the amino terminus, this 106-residue protein is homologous with human serum amyloid protein A (104-residue apoSAA), which is the putative precursor of the 76-residue protein that accumulates in human patients with amyloidosis. Duck serum is shown to contain a protein that is immunologically related and approximately equal in size (12 kDa) to the deposited form in ducks. These results indicate that proteolytic processing of the precursor is not a necessary step in the deposition of amyloid fibrils, at least in the duck. PMID- 3109945 TI - High extracellular Ca2+ and Mg2+ stimulate accumulation of inositol phosphates in bovine parathyroid cells. AB - We examined the effects of the divalent cations Ca2+ and Mg2+ on inositol phosphate accumulation in bovine parathyroid cells prelabelled with [3H]inositol to determine whether the high extracellular Ca2+ and Mg2+-evoked transients in cytosolic Ca2+ in these cells might result from increases in cellular IP3 levels. In the presence of Li+, both Ca2+ and Mg2+ produced rapid, 2-6-fold increases in IP3 and IP2 and a linear increase in IP of 6-8-fold at 30 min. Smaller (1.5-2 fold) increases in IP2 and IP3 were evident within 7.5-15 s upon exposure to high (3 mM) Ca2+ in the absence of Li+. The relative potencies of Ca2+ and Mg2+ (Ca2+ 3-fold more potent than Mg2+) in elevating inositol phosphates were similar to those for their effects in inhibiting PTH release. Fluoride (5 and 10 mM) also produced similar increases in inositol phosphate accumulation, presumably through activation of phospholipase C by a guanine nucleotide (G) protein-dependent process. Thus, high extracellular Ca2+ and Mg2+-induced spikes in cytosolic Ca2+ in bovine parathyroid cells may be mediated by increases in IP3, perhaps through a receptor-mediated process linked to phospholipase C by a G-protein. PMID- 3109946 TI - DNA-dependent RNA polymerase from the chlorotetracycline producing strain of Streptomyces aureofaciens. AB - RNA polymerase from Streptomyces aureofaciens has been purified by polyethyleneimine precipitation followed by chromatography first on DEAE cellulose, then heparin-Sepharose and finally on an aminooxybutylcellulose matrix containing immobilised S. aureofaciens DNA. The enzyme is composed of three subunits of approximately 145, 136 and 44 kDa that are in a ratio of approx. 1:1:2. In many isolations two additional subunits of approximately 68 and 39 kDa and some minor protein bands of approximately 110, 85 and 61 kDa are also present. Thus, the structure of this enzyme is very similar to other bacterial RNA polymerases, exhibiting an alpha 2 beta beta' core and the additional proteins rho and sigma. PMID- 3109947 TI - Solubilization of protein BM-40 from a basement membrane tumor with chelating agents and evidence for its identity with osteonectin and SPARC. AB - Up to 80% of the calcium-binding protein BM-40 could be extracted from a tumor basement membrane with a physiological buffer containing 10 mM EDTA. About half of its amino acid sequence was determined by Edman degradation demonstrating identity with cDNA deduced sequences of bone osteonectin and SPARC. PMID- 3109948 TI - The 3'-orf protein of human immunodeficiency virus shows structural homology with the phosphorylation domain of human interleukin-2 receptor and the ATP-binding site of the protein kinase family. AB - The primary amino acid sequence within a stretch of 25 residues (positions 91 116) of the middle portion of the 3'-orf protein (p27(3')-orf) of the human immunodeficiency virus (HIV) shares structural homology with a highly charged region within the intracytoplasmic phosphorylation domain of human interleukin-2 receptor (IL-2R) and the ATP-binding site of the catalytic subunit of cAMP dependent protein kinase (cAMP-PK) and other members of the protein kinase family. Comparison of the predicted secondary structure within this region of p27(3')-orf with the phosphorylation domain of human IL-2R and the ATP-binding region of the phospho-kinase family of protein suggests that the 3'-orf protein could serve homologous function(s). PMID- 3109949 TI - Immunoreactive forms of caldesmon in cultivated human vascular smooth muscle cells. AB - 150 kDa caldesmon was shown to be characteristic of vascular smooth muscle cells in normal tissue rather than in subculture. Subcultured smooth muscle cells from human aorta contained only the 70 kDa immunoreactive form of caldesmon. During the course of primary culture the amount of 150 kDa caldesmon as well as metavinculin decreased significantly whilst 70 kDa caldesmon became the predominant form, and by the onset of cell division the 150 kDa form was practically substituted by 70 kDa caldesmon. The data show that the predominance of 150 kDa caldesmon is characteristic of contractile smooth muscle cells, while in proliferating cells 70 kDa caldesmon is expressed. PMID- 3109950 TI - Clustering in coated vesicles of polyunsaturated phospholipids segregated from plasma and Golgi membranes of adrenocortical cells. AB - In bovine adrenocortical cells, the fatty acyl chains of the phospholipids have been identified in the membranes of the different cell compartments: plasma membranes, Golgi complex and coated vesicle membranes. An increase in the total number of unsaturation in the fatty acid is demonstrated in the coated vesicle membranes as compared with the plasma and Golgi membranes. Furthermore, it appears that phosphatidylcholine and phosphatidylethanolamine are both enriched in polyunsaturated fatty acyl chains, namely arachidonic and adrenic acids in both types of coated vesicles. Only two of the fatty acids are characteristic of Golgi complex and small coated vesicles, 22:5 (n-6) in PC and 22:6 (n-3) in PE, suggesting that the SCV could originate from the Golgi stacks. A high value of the ratio 22:5 (n-3)/22:6 (n-3) is observed which is, as far as we know, characteristic of adrenal cells. PMID- 3109951 TI - Botulinum neurotoxin inhibits depolarization-stimulated protein phosphorylation in pure cholinergic synaptosomes. AB - Botulinum neurotoxin, a strong blocker of acetylcholine release at peripheral cholinergic synapses, inhibits depolarization-stimulated protein phosphorylation in pure cholinergic synaptosomes isolated from the electric organ of Torpedo marmorata. Moreover, tetrodotoxin has the same effect on protein phosphorylation when cholinergic synaptosomes are depolarized by veratridine. Correlation between presynaptic protein phosphorylation and acetylcholine release is suggested by the fact that botulinum neurotoxin blocks specifically neurotransmitter release without affecting membrane depolarization and calcium fluxes in our synaptosomal preparation. PMID- 3109952 TI - Glucagon-like peptides activate hepatic gluconeogenesis. AB - Piscine (anglerfish, catfish, coho salmon) glucagon-like peptides (GLPs), applied at 3.5 nM, stimulate (1.1-1.9-fold) flux through gluconeogenesis above control levels in isolated trout and salmon hepatocytes. Human GLP-1 and GLP-2 also activate gluconeogenesis, but to a lesser degree than their piscine counterparts. Minor increases of substrate oxidation are noticed at times of peak gluconeogenic activation through GLPs. These hormones, which are derived from the same precursor peptide as glucagon are more potent activators of gluconeogenesis than glucagon when applied at equimolar concentrations, and do not appear to employ cAMP or cGMP as the intracellular messenger in hepatic tissue. PMID- 3109953 TI - Molecular cloning of a new human G protein. Evidence for two Gi alpha-like protein families. AB - The amino acid sequence of a novel G protein alpha subunit (Gx alpha) has been deduced from the nucleotide sequence of a human cDNA clone isolated from a differentiated HL-60 cDNA library. The cDNA encodes a polypeptide of 354 amino acids (Mr 40,519) which is closely related to Gi alpha proteins. The amino acid sequence homology between Gx alpha and human myeloid Gi alpha is 86% with 15 nonconservative substitutions. Gx alpha also shares 86% homology with both rat brain and mouse macrophage Gi alpha but is more homologous (94%) to bovine brain Gi alpha with only 5 nonconservative amino acid differences. G proteins previously termed Gi alpha may fall into at least two distinct groups, with one including human myeloid Gi alpha, rat brain Gi alpha and mouse macrophage Gi alpha; and other Gx alpha and bovine brain Gi alpha. One group probably contains true Gi and the other a new class of G protein whose function remains to be determined. PMID- 3109955 TI - Cumulative ovulation rate in human menopausal/human chorionic gonadotropin treated monkeys: "step-up" versus "step-down" dose regimens. AB - Cumulative ovulation rates in monkeys given human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) on menstrual cycle days 3 to 9 in a "step-up" versus "step-down" protocol were compared with those achieved by hMG only. Using direct ovarian observation to detect sites of follicular rupture, retrograde tubal irrigation to collect eggs or embryos, and serum estradiol and progesterone levels to infer changes in ovarian status, we counted the number of ovulations at intervals of 24, 48, 72, 96, and 120 hours after hCG or comparable intervals without hCG. The data indicate (1) whereas most ovulations occurred on or before day 3 after hCG treatment, when the "step-up" dose regimen was employed additional follicles had ruptured on days 4 and 5; (2) a "step-down" protocol for hMG therapy may better synchronize follicular rupture and reduce susceptibility to delayed ovulations compared with a "step-up" dose regimen; and (3) under hMG stimulation, few follicles would rupture spontaneously (without hCG or luteinizing hormone treatment). PMID- 3109954 TI - Contraceptive steroids and coronary artery atherosclerosis in cynomolgus macaques. AB - The influence of two types of steroidal contraception on the extent of coronary, aortic, carotid, and iliaco-femoral atherosclerosis was assessed in 57 cynomolgus macaques with moderate diet-induced hyperlipoproteinemia. Thirteen animals were treated with an intravaginal ring that released 17 beta-estradiol and levonorgestrel. Fifteen females were treated with an oral contraceptive (OC) composed of ethinyl estradiol and norgestrel. Fifteen females received placebo vaginal rings, and 14 males were untreated. The contraceptive treatments resulted in similar large reductions in plasma high-density lipoprotein (HDL) cholesterol concentrations. Neither treatment influenced the prevalence of coronary artery atherosclerosis. However, treatment with the contraceptive vaginal ring was associated with increased extent of coronary artery atherosclerosis (plaque size) relative to untreated females, whereas treatment with the OC was not. The contrasting effects of the two treatments could not be explained by differences in total plasma cholesterol, HDL cholesterol, or blood pressure. The results suggest that the greater estrogenic influence associated with the ethinyl estradiol-containing OC resulted in inhibition of coronary artery atherosclerosis despite a pronounced progestin-induced lowering of plasma HDL cholesterol concentration and, further, that hormonal balance may have a marked influence on the relationship between plasma lipids and atherogenesis. PMID- 3109956 TI - The effect of a carbon dioxide pneumoperitoneum on rabbit follicular oocytes and early embryonic development. AB - The effect of a carbon dioxide (CO2) pneumoperitoneum and its duration on rabbit follicular oocytes was assessed by evaluating fertilization and subsequent embryonic development rates. CO2 may cross the plasma membrane and form carbonic acid, which liberates H+, thus lowering the intracellular pH. There were no significant differences in arterial pH and [HCO3-] between CO2 and air treatment groups, whereas arterial pCO2 and pO2 were significantly increased in the CO2 treatment group. We found that the duration of pneumoperitoneum, irrespective of type of gas used, was negatively correlated with success of embryonic development. These findings necessitate that more attention be given to the gas used for creation of a pneumoperitoneum during egg retrieval for in vitro fertilization and an attempt be made to minimize duration of the pneumoperitoneum. PMID- 3109957 TI - Gonadotropins augment maturation and fertilization of human immature oocytes cultured in vitro. AB - The inclusion of hMG in the culture medium for immature human oocytes results in improved maturation and fertilization rates. The resulting increased number of conceptuses available for transfer may improve the incidence of IVF pregnancy. PMID- 3109958 TI - The midcycle cervical microbial flora as studied by the weighed-swab method, and its possible correlation with results of sperm cervical mucus penetration tests. AB - Infertile couples undergoing routine investigation for infertility were randomly selected for the study. A quantitative method using weighed swabs was found satisfactory for the study of microbial flora in the midcycle cervical mucus. In 6 of the 20 women, the midcycle cervical mucus was hostile in the sperm cervical mucus penetration tests. The total bacterial counts and the number of species (average, 2.5) isolated from the hostile mucus were significantly greater than those from the receptive mucus (average, 1.3). Only normal vaginal/cervical flora was isolated. Ureaplasma urealyticum was found more frequently in patients undergoing clomiphene citrate therapy (6/10 versus 0/9, P less than 0.03, Fischer's Exact test). PMID- 3109959 TI - The effect of the day of initiation of ovarian stimulation in the day of luteinizing hormone surge and outcome of in vitro fertilization. AB - It was hypothesized that the day of initiation of ovarian stimulation may influence the day of the luteinizing hormone (LH) surge onset and follicular development. Two groups of 52 patients were randomly selected to commence ovarian stimulation on either day 2 or day 4. The mean +/- standard deviation day of the LH surge was 11.0 +/- 0.9 for day 2 and 12.2 +/- 0.9 for day 4 (P less than 0.001), and the day of human chorionic gonadotropin (hCG) administration was 10.7 +/- 1.2 for day 2 and 11.4 +/- 0.9 for day 4 (P less than 0.02). The two groups also differed significantly in the mean number of days of human menopausal gonadotropin (hMG) administration (day 2, 7.4 +/- 2.7, versus day 4, 6.3 +/- 2.5), and the mean number of vials of hMG administered (day 2, 10.4 +/- 3.2, versus day 4, 8.1 +/- 2.9). However, the mean estradiol level on the day of the LH surge or hCG administration, the number of oocytes collected and fertilized, the number of embryos transferred, and the pregnancy rates were not significantly different. In conclusion, the day of the LH surge or hCG administration can be influenced by the day of initiation of ovarian stimulation, and the initiation of ovarian stimulation around day 4 of the menstrual cycle is clinically more efficient than initiation of follicular development early in the follicular phase. PMID- 3109960 TI - Peritoneal fluid environment and infertility. AB - The PF environment is one that hosts the processes of ovulation, gamete transportation, fertilization, and early embryonic development. The cellular and acellular constituents of this dynamic fluid are in a constant interactive state, being influenced by the physiologic events of the menstrual cycle and pelvic disease processes; these constituents probably influence disease manifestation and reproduction. The importance of understanding this zone of early reproductive life has been now recognized. We hope that future investigations will define the exact role(s) of known components and some yet-to-be defined substances of PF in disease processes that affect reproductive function. With better understanding of normal and abnormal events in this pelvic microenvironment, we can develop rationales for novel treatment modalities. PMID- 3109961 TI - Adnexal torsion as a complication of superovulation for ovum retrieval. AB - Adnexal torsion has not been reported previously following hMG/hCG for superovulation induction during an IVF cycle. It is clear that the enlarged ovary from the superstimulation cycle and coital activity contributed to the torsion in this case. Portable ultrasonography helped in making the diagnosis and may be an aid for diagnosis in future cases. Medications used for ovulation induction should be used cautiously and judiciously with close monitoring. Clinicians involved with this type of therapy are obligated to keep a constant watch for such infrequent but devastating complications. PMID- 3109962 TI - Empty follicle syndrome: an entity in the etiology of infertility of unknown origin, or a phenomenon associated with purified follicle-stimulating hormone therapy? PMID- 3109963 TI - Buffering substances of human semen. AB - The quantitative contribution of several components to the BC of human semen has been investigated. The role of spermatozoa is negligible (less than 2%). Both the high-molecular components (proteins) and the HCO3-/CO2 system contribute about 25% to the BC. Therefore, about 50% of the BC of semen must be due to low molecular weight components other than HCO3-/CO2. PMID- 3109964 TI - Pulsatile intravenous gonadotropin-releasing hormone for ovulation-induction in infertile women. II. Analysis of follicular and luteal phase responses. AB - Pulsatile intravenous gonadotropin releasing hormone (IV-GnRH) was used in 36 infertile patients with primary amenorrhea (n = 5), secondary amenorrhea due to hypothalamic chronic anovulation (HCA) (n = 22), hyperprolactinemia (n = 1) or polycystic ovary syndrome (PCOS) (n = 5), and oligomenorrhea (n = 3), using several dosage and timing regimens. Early follicular phase responses showed four patterns: type 1 consisted of a delayed follicle-stimulating hormone (FSH) peak and was seen with severe hypothalamic suppression (n = 4); type 2 consisted of a brisk and dominant FSH peak on the first day of treatment, and occurred with mild to moderate hypothalamic suppression (n = 19); type 3, which consisted of an FSH peak accompanied by an immediate and exaggerated luteinizing hormone (LH) rise, occurred with mild PCOS and some cases of HCA (n = 5); and type 4, in which LH levels were high to begin with and neither FSH nor LH levels rose with GnRH, occurred with severe PCOS (n = 2). Exaggerated estradiol responses within 24 hours of therapy were seen in eight cycles: in four cases no ovarian abnormality was apparent; in three cases a dominant follicle was already present; and in one case ovarian hyperstimulation was diagnosed ultrasonographically. With standard human chorionic gonadotropin luteal phase support, luteal phase defects were rare with HCA but common with PCOS. PMID- 3109965 TI - Postmenarchal evolution of endocrine pattern and ovarian aspects in adolescents with menstrual irregularities. AB - Ninety-five adolescents with menstrual irregularities persisting since menarche were studied and the data analyzed in relation to gynecologic age. In each year, in the premenstrual phase, luteinizing hormone (LH), testosterone (T), and androstenedione (delta 4A) values were higher than those of adults. Estrone (E1), estradiol (E2), 17-hydroxyprogesterone (17-OHP), progesterone (P), and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) gradually increased up to adult values correlating with gynecologic age. By ultrasound, nearly half the ovaries were multicystic and ovarian volume was greater than that of adults in each gynecologic year. When the data were classified as ovulatory or anovulatory, ovulation appeared to be a dynamic process characterized by ovaries similar to those of adults and by increasing hormonal levels correlated to gynecologic age. By contrast, in anovulatory cycles, mean T, delta 4A, and LH values were stable in each year and constantly higher than in ovulatory cycles and adult controls. These findings suggest that, despite persistent irregular cycles, some adolescents normalize all endocrine and ovarian parameters toward maturity, while subjects with persistent irregular anovulatory cycles maintain marked hyperandrogenism, increasingly high LH values, and enlarged multicystic ovaries. PMID- 3109966 TI - Interaction of protein- and DNA-loaded liposomes with sperm cells. AB - Liposomes were loaded with fluorescence-labelled serum albumin and their interaction with mouse spermatozoa was examined in a fluorescence microscope. In the presence of polyethylene glycol 1500, fluorescence became unevenly distributed along the entire body of mature spermatozoa, mostly in the form of aggregates, indicating adsorption of liposomes to the surface of the cells. The fluorescence could be largely removed by washing the cells. In the case of immature sperm cells, fluorescence was evenly distributed on the cells and was not removed by extensive washing, suggesting an internalization of the labelled albumin. A more direct evidence for the entrance of liposome-entrapped macromolecules into the immature sperm cells was provided by autoradiography: radioactivity was found in discrete spots in spermatocytes upon their incubation with liposomes containing isotopically labelled DNA. PMID- 3109967 TI - [Testing of new culture media in the culture diagnosis of Neisseria gonorrhoeae]. PMID- 3109968 TI - Ultrastructural characterization of leucocytes in the pronephros of carp (Cyprinus carpio, L.). AB - In the pronephros of carp (Cyprinus carpio, L.) the following cells were found and ultrastructurally characterized: erythrocytes; lymphocytes and plasma cells; thrombocytes; neutrophilic, eosinophilic and basophilic granulocytes; phagocytic reticular cells and monocytes and non-phagocytic reticular cells. The cells could be separated on a Percoll continuous density gradient and relatively pure fractions could be obtained. In vitro phagocytosis of bacteria (Bacillus megaterium) was found in monocytes and neutrophilic granulocytes, while basophilic and eosinophilic granulocytes engulfed bacterial cells without actual endocytotic uptake. PMID- 3109969 TI - Inhibition of frog SK effector-target cell binding. AB - Substances known to inhibit mammalian NK cell activity during the first stage of lysis (i.e., effector cell-target cell binding) will also inhibit frog SK cell activity. We analyzed target cell lysis after conjugate formation between one target cell and at least one effector cell. Using frog SK effector cells and frog allogeneic and mammalian tumor target cells, we demonstrated that EDTA, the Ca+2 and Mg+2 chelating agent, but not EGTA, the Ca+2 chelating agent, inhibited binding. Thus, Mg+2 is required for conjugate formation. The inhibitory effects of EDTA were at least partially reversible following removal of EDTA. Binding also required membrane fluidity since pretreatment of targets with glutaraldehyde prevented effector cell binding. Adding glutaraldehyde after conjugate formation increased lysis. Modification of target cell surface proteins by DMSO and trypsin also inhibited binding of effector and target cells. Substances inhibiting binding decreased lysis as measured by 51Cr-release from target cells. Inhibition of binding between SK effector and target cells adds further support to our view that natural or spontaneous killing of foreign cells may be one of the most primitive immuno-defense mechanisms. PMID- 3109970 TI - Reactions of hemocytes of immune and non-immune Galleria mellonella larvae to Proteus mirabilis. AB - Immune larval Galleria mellonella removed live Proteus mirabilis from the hemolymph less effectively than did non-immune larvae. This was attributed to a decline in total hemocyte counts, levels of plasmatocytes and granulocytes and hemocyte adhesion capacity. Immune serum possessed factors which reduced bacterial adhesion to the hemocytes. This was not due to altering bacterial surfaces but rather to irreversible suppression of hemocyte activity. PMID- 3109971 TI - Proof of proteolytic activity of hemorrhagic toxins, HR-2a and HR-2b, from Trimeresurus flavoviridis venom. AB - Two hemorrhagic toxins, HR-2a and HR-2b were originally isolated from Trimeresurus flavoviridis (Habu) venom by Takahashi and Ohsaka (1970). It was reported by the original investigators that no proteolytic activity was detected when casein was used as the substrate. HR-2a and HR-2b were isolated in this laboratory and their proteolytic activities were tested using a variety of different substrates and assay methods. HR-2a and HR-2b were found to contain, respectively, 200 and 219 amino acid residues. Toxicological and biochemical properties of HR-2a and HR-2b were further investigated and are reported in this paper. PMID- 3109972 TI - Microheterogeneity of melanosome-bound tyrosinase from the Harding-Passey murine melanoma. AB - This study was directed towards the characterization of the origin of the microheterogeneity displayed by mammalian tyrosinase, the enzyme responsible for pigmentation in mammals. Tyrosinase was purified from the Harding Passey murine melanoma, fractionated into a continuous series of subisozymic forms, and analyzed using various chemical and immunological probes. Treatment with neuraminidase revealed that all the forms had similar amounts of sialic acid, and reactivity with various carbohydrate specific lectins showed that the isozymes also contained subterminal galactose, N-acetylglucosamine, and mannose, but lacked alpha-fucose. Amino acid composition data indicated that the polypeptides of all the forms had identical residue contents. The sum of the evidence further supports the theory that the isozymic forms demonstrable for mammalian tyrosinase represent intermediate processing stages of the enzyme from the nascent protein chain to the fully glycosylated, high molecular weight form of tyrosinase that is localized within melanin granules. PMID- 3109974 TI - Identification in Tetrahymena pyriformis of 3-hydroxy-3-methyl glutaryl coenzyme a lyase: its purification and properties. AB - The major HMG-CoA utilizing enzyme activity in T. pyriformis has been determined to be HMG-CoA lyase. The enzyme was purified 32-fold to a specific activity of 431 units/mg from a mitochondrial fraction. Sephacryl S-200 chromatography gave an estimated molecular weight of 50,000 daltons for the HMG-CoA lyase. SDS gel electrophoresis revealed two bands stained by Coomassie Blue--a major band of 50,000 daltons and a minor band of 25,000 daltons. The latter is believed to be an impurity in the preparation. The enzyme has a pH optimum of 9.0, is stimulated slightly by sulfhydryl reagents, and requires a divalent cation for maximum activity. The KM for HMG-CoA is 15 microM. PMID- 3109973 TI - Monoclonal antibodies to nonhistone proteins associated with human colon cancer nuclear matrix. AB - Hybridoma technology was applied in an effort to create highly specific probes for nonhistone proteins associated with human colon cancer nuclear matrix. Three stable monoclonal antibodies producing cloned cells No. 39, 54 and 58 are described here. All these antibodies showed high reactivity with human colon tumor nuclear matrix. Both antibodies No. 39 and 58 showed an extensive cross reactivity at high concentration of normal colon nuclear matrix. The antigens were determined to be a heterogeneous group of proteins with a major antigen of molecular weight of 140,000 for antibody No. 54 subclone 54-c-5-6 and two major antigens of molecular weight for 105,000 and 116,000 for antibody No. 39 subclone 39-d-11-12. Immunohistochemical localization of the antigens by the horseradish peroxidase bridge method demonstrated their presence in the nuclei. PMID- 3109975 TI - Copurification and separation of beta-galactosidase and sialidase from porcine testis. AB - A soluble sialidase was copurified apparently as an enzyme complex with acid beta galactosidase from porcine testis. The sialidase exhibited its maximum activity at acidic pH. It was efficiently active towards 4-methylumbelliferyl-alpha-D-N acetyl-neuraminic acid and sialyllactose, relatively inactive towards glycoproteins, and had little activity towards glycolipids. The complex could be separated by sucrose gradient centrifugation or isoelectric focusing. The separated enzymes had molecular weights about 600,000 for beta-galactosidase and more than about 1,000,000 for sialidase by Sepharose 4B gel filtration. SDS polyacrylamide gel electrophoresis of the beta-galactosidase showed three protein bands with molecular weights of 63,000, 31,000 and 20,000. PMID- 3109976 TI - Stimulation of luteinizing hormone release by melittin and phospholipase A2 in rat pituitary cells. AB - Gonadotropin release in rat pituitary monolayer cultures was stimulated by phospholipase A2, as well as by its activator melittin. A dose-dependent stimulation of luteinizing hormone secretion by melittin was observed in a dose range of 10(-8) to 10(-4) M. A higher dose (1 mM) melittin had a sub-optimal effect. The stimulatory action of melittin was calcium-dependent and blocked by phospholipase A2 inhibitors, chloroquine and quinacrine. Similar to melittin, phospholipase A2 enhanced the effect of LH release in a dose range of 0.1-100 units/ml. The effect of this enzyme was also calcium-dependent with optimal calcium concentrations at 1.5 mM, as obtained also for melittin. In superfusion experiments, the stimulatory action of melittin and phospholipase A2 was reproducible in their effects on LH release in gonadotrophs. In addition, melittin (10(-7) M) stimulated LH and 3H-arachidonic acid efflux in superfused pituicytes following prelabelling with radiolabelled arachidonate. These data suggest that phospholipase A2, which releases arachidonic acid from phospholipids, may participate in controlling gonadotropin secretion in gonadotrophs, since arachidonic acid and its metabolites have previously been found to enhance gonadotropin release. PMID- 3109977 TI - Epinephrine effect on arachidonic acid biosynthesis in isolated adrenocortical cells. AB - The in vivo and in vitro effect of epinephrine on the incorporation and desaturation of [1-14C]eicosa-8,11,14-trienoic acid was studied in isolated adrenocortical cells of rats. Control cells incubated at different substrate concentrations and for different periods of time were able to incorporate eicosatrienoic acid and to desaturate it to arachidonic acid. The ultrastructural study demonstrated that most of the cells belonged to the zona fasciculata and presented a good preservation. When the cells were isolated from rats killed 7 and 12 h after the administration of a single dose of epinephrine, a decrease in the incorporation and desaturation of 20:3n6 was observed. The effect on the desaturation was independent from the incorporation of the acid, and it was also observed in the microsomes of the decapsulated adrenal gland from rats treated with epinephrine. The fine structure of adrenocortical cells did not show changes after the treatment with epinephrine. The addition of the hormone to the incubation medium containing cells isolated from untreated rats produced no effect on arachidonic acid biosynthesis, indicating that the effect of epinephrine would be indirect, through either a metabolic or a hormone mediator. PMID- 3109978 TI - Epidermal growth factor and its receptor. AB - Epidermal growth factor (EGF) binds with high affinity and specificity to a single site on the external domain of its transmembrane receptor to activate the tyrosine protein kinase activity of its cytoplasmic portion. The EGF receptor gene is amplified and over-expressed in several human tumors, suggesting that increased concentrations of the proto-oncogene leads to constitutive activity similar to that seen with oncogene erb B. Synthesis and degradation of the EGF receptor are regulated, in addition, covalent modification by phosphorylation regulates activity of the receptor protein. Intramolecular self-phosphorylation of Tyr1173 removes a competitive inhibitory constraint to enhance phosphorylation of substrates. Phosphorylation of Thr654 by protein kinase C decreases high affinity EGF binding and EGF-stimulated tyrosine protein kinase activity, providing a mechanism for heterologous regulation of the EGF receptor by tumor promoters and other ligand X receptor complexes. Extensive regulation contributes to normal growth control, abrogation of regulatory controls contributes to uncontrolled growth as seen with erb B transformation and EGF receptor gene amplification in human tumors. PMID- 3109979 TI - Dopaminergic regulation of polyamine synthesis in the rat pituitary gland. AB - The biosynthesis of polyamines, a group of growth-related amines, varied in the rat pituitary gland with the different stages of the estrous cycle. The activity of ornithine decarboxylase (ODC), which catalyzes the rate-limiting step in the biosynthesis of polyamines, was greatly increased in the pituitary gland during the evening of proestrus. Ovariectomy resulted in a disappearance of this cyclic change in polyamine synthesis, whereas estrogen treatment of the ovariectomized rats gave rise to daily afternoon peaks in pituitary ODC activity. Like the prolactin cells, pituitary polyamine biosynthesis appeared to be regulated by dopamine. The induction of ODC activity in the pituitary gland during proestrus or after estrogen treatment was almost completely repressed by bromocriptine, a dopaminergic compound. The dopamine antagonist haloperidol, on the other hand, was a potent inducer of pituitary ODC activity. Neither pituitary DNA synthesis nor prolactin secretion, which both are induced by estrogen, were affected by inhibition of polyamine synthesis, suggesting a biological function of the pituitary polyamines unrelated to these events. PMID- 3109980 TI - Deletion of lysine 13 alters the structure and function of parathyroid hormone. AB - A peptide of unknown structure was found as a side product in a commercial preparation of the 1-34 fragment of bovine parathyroid hormone (PTH). CNBr cleavage and amino acid analysis showed that this peptide is the des-lys-13 form of 1-34 bovine PTH. The peptide thus represents a deletion mutant of PTH and structure-function studies are of interest. This peptide was a full agonist in the adenylyl cyclase bioassay for PTH, but its potency was about 5% of that found for the complete 1-34 peptide. Proton NMR studies showed that the pK values for the histidine residues in the des-lys-13 form were essentially identical to those of the intact peptide. However, pH-dependent changes in the chemical shifts for the tryptophan protons (residue 23) and several unidentified methyl group resonances were observed in the des-lys peptide. The latter are major shifts and probably represent ring-current effects; these were not seen in the intact 1-34 peptide. The results show that Lys-13 is important in the folding of the active domain of PTH, and are interpreted in the context of a previously published model for the folding of this hormone. PMID- 3109981 TI - The enhancer of split locus and neurogenesis in Drosophila melanogaster. AB - Enhancer of split (E(spl)) is one of a group of so-called neurogenic genes of Drosophila. We describe two different types of E(spl) alleles, dominant and recessive, which exert opposite effects on both central and peripheral nervous system development. The only extant dominant allele determines a reduction in the number of central neurons and peripheral sensilla; this phenotype is not reduced by a normal complement of wild-type alleles. Since animals carrying a triploidy for the wild-type locus develop similar defects, the dominant allele is probably the result of a gain-of-function mutation. Several recessive alleles, obtained as revertants of the dominant allele, are loss-of-function mutations and determine considerable neural hyperplasia. The present evidence suggests that neural defects of E(spl) mutants are due to defective segregation of neural and epidermal lineages, leading to neural commitment of less or of more cells than in the wild type, depending upon whether the animals carry the dominant or any of the recessive alleles, respectively. Therefore, E(spl) formally behaves as a gene switching between neural and epidermal pathways. PMID- 3109982 TI - Cellular localization of HSP23 during Drosophila development and following subsequent heat shock. AB - The low-molecular-weight heat-shock protein HSP23 is synthesized in the absence of heat shock during Drosophila development. Here, I present a quantitative analysis of this phenomenon and describe the cellular localization of this protein during normal development and after a subsequent heat shock. HSP23 is first detected in the late third instar larvae and continues to accumulate reaching a maximum level in late pupae. In a 1-week-old adult, HSP23 can no longer be detected. Following lysis of whole pupae, HSP23 is found in the soluble lysate fraction in a form which sediments between 10 and 20 S. Exposure of larvae, pupae, and the adult fly to heat stress (37 degrees C) results in an increased amount of HSP23 which, however, is recovered in an insoluble particulate form following insect lysis. During recovery from heat shock, HSP23 is again found in the soluble 10- to 20-S lysate fraction. In pupae which are exposed to a severe heat stress (41 degrees C) HSP23 remains in the pellet fraction after the heat stress and no pupae are able to emerge as adult flies. However, when pupae are first exposed to a mild heat-shock treatment prior to the 41 degrees C stress, the thermotolerance process is induced and HSP23 is again rapidly found in the soluble lysate fraction during the recovery from heat shock. These observations suggest a possible correlation between the survival of pupae after heat shock and the recovery of HSP23 in the soluble lysate fraction as 10- to 20-S structures after the heat shock. PMID- 3109983 TI - Relationships between extracellular pH, intracellular pH, and gene expression in Dictyostelium discoideum. AB - A variety of studies have shown that differentiation of Dictyostelium discoideum amoebae in the presence of cAMP is strongly influenced by extracellular pH and various other treatments thought to act by modifying intracellular pH. Thus conditions expected to lower intracellular pH markedly enhance stalk cell formation, while treatments with the opposite effect favor spores. To directly test the idea that intracellular pH is a cell-type-specific messenger in Dictyostelium, we have measured intracellular pH in cells exposed to either low extracellular pH plus weak acid or high extracellular pH plus weak base using 31P nuclear magnetic resonance (NMR). Our results show that there is no significant difference in intracellular pH (cytosolic or mitochondrial) between pH conditions which strongly promote either stalk cell or spore formation, respectively. We have also examined the effects of external pH on the expression of various cell type-specific markers, particularly mRNAs. Some mRNAs, such as those of the prestalk II (PL1 and 2H6) and prespore II (D19, 2H3) categories, are strongly regulated by external pH in a manner consistent with their cell-type specificity during normal development. Other markers such as mRNAs D14 (prestalk I), D18 (prespore I), 10C3 (common), or the enzyme UDP-galactose polysaccharide transferase are regulated only weakly or not at all by external pH. In sum, our results show that modulation of phenotype by extracellular pH in cell monolayers incubated with cAMP does not precisely mimic the regulation of stalk and spore pathways during normal development and that this phenotypic regulation by extracellular pH does not involve changes in intracellular pH. PMID- 3109984 TI - A genetic and developmental analysis of mutations in the Deformed locus in Drosophila melanogaster. AB - Individuals expressing recessive mutations in the Deformed (Dfd) locus of Drosophila melanogaster were examined for embryonic and adult defects. Mutant embryos were examined in both scanning electron microscope and light microscope preparations. The adult Dfd recessive mutant phenotype was assessed in somatic clones and in survivors homozygous for hypomorphic alleles of the gene. The time of Dfd+ action was determined by studying a temperature conditional allele. Dfd+ is required in three embryonic cephalic segments to form a normal head. Mutant embryos of Dfd display defects in derivatives of the maxillary segment, of the mandibular segment, and of some more anterior segments. In the adult fly, defects are seen in the posterior aspect of the head when the gene is mutant. A transformation from head to thoracic-like tissue is seen dorsally and a deletion of structures is seen ventrally. Shift studies utilizing a temperature conditional allele have shown that the gene product is necessary during at least two periods of development, during embryonic segmentation and head involution and during the late larval and pupal stages. From these studies we conclude that Dfd is a homeotic gene necessary for proper specification of both the embryonic and the adult head. PMID- 3109985 TI - Epidermal growth factor potentiates the induction of ornithine decarboxylase activity by prostaglandins in embryonic palate mesenchymal cells: effects on cell proliferation and glycosaminoglycan synthesis. AB - Epidermal growth factor (EGF) and prostaglandins (PGs) have been implicated in the regulation of a number of developmental processes in the mammalian embryonic palate. Normal palatal ontogenesis is dependent on the presence and quite possibly on the interaction of various hormones and growth factors. The interaction between EGF and PGs in regulation of murine embryonic palate mesenchymal (MEPM) cell growth and differentiation was therefore investigated by monitoring the activity of ornithine decarboxylase (ODC), the principle and rate limiting enzyme of polyamine biosynthesis. ODC activity is tightly coupled to the proliferative and differentiative state of eukaryotic cells and therefore serves as a reliable indicator of such cellular functions. Treatment of confluent cultures of MEPM cells with EGF (1-50 ng/ml) resulted in a dose-related increase in ODC activity, while similar treatment with either PGE2 or PGF2 alpha (at concentrations up to 1 microM) did not elicit a dose-dependent increase in enzyme activity. Concurrent treatment of MEPM cells with EGF (20 ng/ml) and either PGE2 or PGF2 alpha (0.1-10000 nM) resulted in a marked prostaglandin dose-dependent induction of ODC activity, suggesting a strong cooperative interaction between these factors. ODC activity was maximal by 4 to 8 hr and could be completely inhibited by preincubation of the cells with actinomycin D or cycloheximide, indicating that de novo synthesis of RNA and protein is necessary for enzyme induction. Stimulation of ODC activity by EGF and PGE2 in these cells was not positively correlated with the level of cellular DNA synthesis but did result in a ninefold increase in the synthesis of extracellular glycosaminoglycans (GAGs), a key macromolecular family implicated in palatal morphogenesis. Stimulation of GAG synthesis was significantly inhibited by the administration of 5 mM DFMO (an irreversible inhibitor of ODC), indicating that the marked increase in GAG production was dependent, in part, on the induction of ODC activity by EGF and PGE2. Qualitative analysis of the palatal GAGs indicated that synthesis of several major classes of GAGs was stimulated. Collectively these data demonstrate a cooperative interaction between EGF and PGs in the induction of ODC activity. Such activity may serve to regulate the synthesis of GAGs, which are instrumental in mammalian palatal ontogenesis. PMID- 3109986 TI - The defective dorsal discs gene of Drosophila is required for the growth of specific imaginal discs. AB - The wild-type allele of the gene defective dorsal discs (ddd) is required for the normal development of the dorsal thoracic discs in Drosophila melanogaster. In ddd mutant larvae the dorsal discs (wing, haltere, and humeral) are greatly reduced in size or absent while the ventral discs (leg) are unaffected. We have examined the function of the ddd+ gene in wing development. The ddd+ product is not involved in the initial determination of wing cells but rather is required for their subsequent proliferation during the larval period. Analysis of chimaeras shows that there is a requirement for ddd+ gene expression in wing discs, but it is sufficient for normal development that only some cells in a disc express the gene. We propose that the ddd+ product is involved in the synthesis of a factor which is required for the normal growth of wing discs and which can be transferred between wing disc cells. PMID- 3109987 TI - Various strains of BCG vaccine and genetic control of the immune response of mice. AB - Numerous field trials of BCG vaccine, undertaken to evaluate its effectiveness in the prophylaxis of human tuberculosis, indicated that the levels of protection achieved were not uniform. Most probable factors influencing these results are: partial protection due to atypical mycobacteria, tuberculosis expectancy in different population, nutritional and socio-economic factors, potency of BCG vaccines, and genetic factors controlling the host immune response. Specific and non specific hallmarks of cell-mediated immunity after BCG infection were analysed in various outbred, inbred and recombinant lines of mice, testing the capacity of different preparations and strains of BCG vaccine. Results of such studies did show that the by far most important factor involved the type of immune response related to gene(s) controlling the natural resistance and the expression of C.M.I. Consequences for future mass and individual BCG vaccination as well as the proper integration of BCG vaccination in antituberculous policy are discussed. PMID- 3109989 TI - Cognitive function in children with epilepsy. PMID- 3109988 TI - Expression of cytoplasmic islet cell antigens by rat pancreas. AB - A major problem in standardization of the islet cell cytoplasmic antibody (ICA) assay is variation in sensitivity of the different human pancreas substrates used in individual laboratories. To circumvent this problem, we have developed an assay that utilizes Wistar-Furth rat pancreas as substrate, an anti-islet monoclonal antibody (A2B5) to identify islets and fluorescein-conjugated protein A to identify patient autoantibodies. Sera from 85 control subjects, 27 type I diabetics, and 17 subjects at high risk for developing type I diabetes were assayed in parallel with our standard ICA assay on human pancreas substrate and with Wistar-Furth rat pancreas as substrate. Two sera from control subjects (2 of 85) were ICA positive with rat pancreas compared to 1 of 85 with human pancreas substrate. Sera from 11 of 27 type I diabetics and 15 of 17 sera from high-risk subjects were ICA positive with either rat or human pancreas substrate. A correlation between the specific islet fluorescence readings on human and rat pancreas sections was found with sera from high-risk and control subjects. Furthermore, end-point titers of an ICA-positive serum were identical with both assays. Finally, incubation of an ICA-positive serum with glycolipids, extracted from either human or Wistar-Furth rat pancreas, blocked subsequent ICA binding. These findings suggest that Wistar-Furth rat pancreas expresses an identical or similar autoantigen to human pancreas. PMID- 3109990 TI - Effect of rioprostil, a synthetic prostaglandin E1 on meal-stimulated gastric acid secretion and plasma gastrin levels in humans. AB - The effects of rioprostil (a newly developed synthetic prostaglandin E1 analogue) on meal-stimulated gastric acid secretion was evaluated in 8 healthy human volunteers. Gastric acid output was measured by intragastric titration on 4 different occasions. The following procedure was invariably employed: after a basal period of 45 min, 5 peptone meals (8%, 500 ml each) were given intragastrically in 45-min intervals and gastric acid output was measured continuously. 45 min after the first meal, either placebo or 150, 300 or 600 micrograms of rioprostil were given intragastrically in a randomized order and on different days. 15 min later, the second meal was given and intragastric titration continued. Rioprostil caused a dose-dependent inhibition of the 3-hour integrated gastric acid response to the peptone meals. The percentage of inhibition was 41, 68 and 79%, respectively, for 150, 300 and 600 micrograms of rioprostil. Whereas the inhibition by the two highest doses was statistically significant, this was not the case for the lowest dose of rioprostil. The integrated 3-hour plasma gastrin response to the peptone meals was not significantly changed by any of the doses of rioprostil. No significant adverse effects were observed with rioprostil. PMID- 3109991 TI - The polyol pathway and glucose 6-phosphate in human endothelial cells cultured in high glucose concentrations. AB - In an attempt to identify the mechanisms underlying the ill effects of high glucose previously described in cultured human endothelial cells, we have investigated in these cells the activity of the polyol pathway and accumulation of glucose 6-phosphate, a powerful agent of non-enzymatic glycosylation. Sorbitol accumulation varied among different batches of cells (primary cultures). In presence of 5 mmol/l glucose the cellular sorbitol content ranged from 0.04 to 0.12 nmol/10(6) cells. When cells were exposed to 20 mmol/l glucose the sorbitol content increased by 2- to 3-fold to concentrations of 0.08-0.38 nmol/10(6) cells (p less than 0.01). Addition to the culture medium of 100 mumol/l Sorbinil, an inhibitor of aldose reductase, resulted in a substantial inhibition of sorbitol accumulation throughout the 14 days in culture, but the degree of inhibition varied inversely with the duration of cell exposure to high glucose (70% inhibition in cells exposed to high glucose and Sorbinil for 1-3 days versus 14% inhibition in cells exposed for 14 days, p less than 0.01). Sorbinil treatment failed to improve even slightly the abnormalities in cellular replication induced by high glucose. The cellular content of glucose 6-phosphate was augmented 3-fold by exposure to 20 mmol/l glucose (p less than 0.001). In conjunction with other studies these results indicate that in this model the polyol pathway is not an osmotically or metabolically important mechanism of glucotoxicity, and that the inhibitory activity of Sorbinil on the polyol pathway of human tissues may be a function of their length of exposure to hyperglycaemia. The consequences of intracellular accumulation of glucose 6-phosphate await investigations. PMID- 3109993 TI - Effect of workup strategy on the cost-effectiveness of fecal occult blood screening for colorectal cancer. AB - Physicians respond to a positive fecal occult blood test with a variety of workup strategies. To study the effect of the choice of strategy on the net costs and health benefits of colorectal cancer screening using this test, we used a decision analysis model to compare seven strategies that physicians might choose to examine a positive "screenee." Strategies using rigid or flexible sigmoidoscopy alone are not only insensitive, but also have high cost effectiveness ratios. The strategy of air contrast barium enema alone had the lowest cost-effectiveness ratio. Rigid sigmoidoscopy combined with barium enema had a lower cost-effectiveness ratio than primary colonoscopy, but the strategy of primary colonoscopy could have an equal or better ratio depending on assumptions about test costs and the benefit of removing benign polyps. The primary colonoscopy strategy is both more effective and less costly than the combination of flexible sigmoidoscopy and barium enema. The optimal strategy will vary with local factors, and with the perspective of the decision-maker. PMID- 3109994 TI - Persistent pneumoperitoneum after percutaneous endoscopic gastrostomy. PMID- 3109992 TI - Aldose reductase in the BB rat: isolation, immunological identification and localization in the retina and peripheral nerve. AB - Aldose reductase was purified from testis of non-diabetic BB rats using DEAE cellulose, hydroxylapatite and sephadex G-100 column chromatography. The molecular weight of the isolated enzyme was found to be 36,500 +/- 1000. Antibody against the isolated enzyme was raised in rabbits. It was purified by affinity chromatography, characterised by double immunodiffusion and Western blot analysis and used to localize the enzyme in retina and in peripheral nerve of the BB rat. In the retina, aldose reductase immunoreactivity was seen in the ganglion cells, Muller cell processes, retinal pigment epithelium and in the pericytes and endothelial cells of retinal capillaries. In peripheral nerve, aldose reductase immunoreactivity was found in the paranodal cytoplasm of Schwann cells and in pericytes and endothelial cells of endoneurial capillaries. PMID- 3109995 TI - Percutaneous endoscopic gastrostomy and crepitus. PMID- 3109997 TI - [Stimulation of ovarian function with gonadotropins following suppression of endogenous gonadotropin secretion by long-term infusion of the LHRH analog buserelin]. AB - The treatment of infertile women by gonadotropins is more effective in hypogonadotropic than in normogonadotropic ovarian insufficiency. In order to induce a hypogonadotropic state the luteinizing hormone-releasing hormone analog (LHRHA) buserelin was administered in eight cycles of four infertile patients suffering from luteal phase defect. Buserelin was infused subcutaneously in a dosage of 400 micrograms/d for 26-44 days using a portable external osmotic minipump system. Following suppression of estradiol-17 beta below 35 pg/ml within 11 +/- 5 days, gonadotropins were injected intramuscularly to stimulate ovarian function. In all cycles treated, ovulation and formation of a functional corpus luteum were observed without signs of premature luteinization. Whereas constant administration of LHRHA by a slow release system seems very useful for long-term reversible suppression of follicular maturation, further studies should evaluate the clinical usefulness of combined LHRHA/gonadotropin treatment in cases of infertility. PMID- 3109996 TI - Medications for use in patients with enteral feeding tubes. PMID- 3109998 TI - [Effect of serum prolactin on cycle stimulation and fertilization of human oocytes]. AB - During cycle stimulation for in-vitro fertilisation (IVF) some patients develop hyperprolactinaemia. Since prolactin (PRL), being an aromatase inhibitor, can interfere with follicular fluid steroid metabolism, we examined the influence of high serum PRL levels on the endocrine response and fertilisation rate of oocytes. 33 consecutive patients stimulated by hMG/hCG for IVF were included in this study. Two groups of patients were established: Group 1 consisting of 18 patients with serum PRL levels less than or equal to 25 ng/ml, and group 2 containing 15 patients, who developed PRL levels greater than 25 ng/ml during cycle stimulation. The serum oestradiol (E2), progesterone (P) and PRL levels 3, 2 and 1 day before and at the day of follicle puncture were evaluated. The decrease of E2 levels at the day of oocyte retrieval was significantly steeper in group 1. The P levels 2 days before oocyte retrieval were significantly higher in group 1 indicating the onset of preovulatory luteinization. Luteinization after the hCG injection was more effective in group 1 resulting in significantly higher P levels. Fertilisation and cleavage rates were significantly higher in patients with normal PRL levels. High serum PRL levels therefore might indicate an interference in follicular and oocyte development leading to oocytes of inferior quality. PMID- 3109999 TI - [Histometric studies of placental villi in Rh incompatibility]. AB - The delay in maturation of placental terminal villi in cases of Rh incompatibility has often been described. The terminal villi of sixteen placentas from pregnancies complicated by Rh-incompatibility histometric were studied. Twenty-two placentas of healthy mothers who had born healthy babies after normal pregnancies served as a control group. The severity of the Rh-incompatibility was classified according to the clinical histories of the newborns and the criteria of Liley. The average area of a cross-section of a terminal villus was 3402 microns 2 (control group 2150 micronsoff; the degree of vascularization was calculated to be 6.5% (control group 30.5%). The other villous parameters measured or calculated show that maturation of the placenta is extremely retarded in cases of Rh-incompatibility. This failure in differentiation can not be compensated for by an enlargement of the organ as a whole. It was shown that the changes in the placental villi are closely correlated to the severity of the fetal disease. PMID- 3110000 TI - [Decreasing Rhesus serum antibody titer in pregnancy with Rhesus constellation]. AB - Without Rh-IgG prophylaxis the incidence of rhesus sensitisation increases in D negative women with the number of subsequent pregnancies. However, our case report of a d-negative multipara demonstrates that foetal erythroblastosis does not necessarily occur in a pregnancy with initially high anti-D titres. PMID- 3110001 TI - [Cyclophosphane treatment of patients with partial red cell aplasia]. PMID- 3110002 TI - [Oligoclonal paraproteinemia in partial red cell aplasia of the bone marrow]. PMID- 3110003 TI - Effects of microwave irradiation on some membrane-related processes in bacteria. AB - In a series of experiments performed on intact cells or spheroplasts of E. coli and Bac. subtilis a possibility of non-thermal effects induced by continuous microwave irradiation of a low power density (at wave length range from 0.0 to 7.8 mm) was studied. Thymidine and thymine uptake, leakage of potassium and hydrogen ions as well as the uptake of the transforming DNA by the component cells of Bac. subtilis were shown to be affected in a way typical of that due to heating of a sample. No specific dependence of the effects observed on wavelength was found. PMID- 3110004 TI - A test of neutral molecular evolution based on nucleotide data. AB - The neutral theory of molecular evolution predicts that regions of the genome that evolve at high rates, as revealed by interspecific DNA sequence comparisons, will also exhibit high levels of polymorphism within species. We present here a conservative statistical test of this prediction based on a constant-rate neutral model. The test requires data from an interspecific comparison of at least two regions of the genome and data on levels of intraspecific polymorphism in the same regions from at least one species. The model is rejected for data from the region encompassing the Adh locus and the 5' flanking sequence of Drosophila melanogaster and Drosophila sechellia. The data depart from the model in a direction that is consistent with the presence of balanced polymorphism in the coding region. PMID- 3110005 TI - Care must be special for the severely demented. PMID- 3110006 TI - Genetic localization of a regulatory site necessary for the production of the glue protein P5 in Drosophila melanogaster. PMID- 3110007 TI - The nucleotide sequence and gene organization of the gerA spore germination operon of Bacillus subtilis 168. AB - The nucleotide sequence of the second and third genes in the Bacillus subtilis spore germination locus, gerA, has been determined and the amino acid (aa) sequence was derived. Two open reading frames (ORFs), corresponding to genes II and III, encode 364-aa residue and 373-aa residue polypeptides, respectively. The gene II product, Mr 41,257, would contain long stretches of hydrophobic aa residues and may be a membrane protein; the gene III product, Mr 42,363, is relatively hydrophilic but possesses an apparent signal peptide for transfer across, and perhaps localisation on, a membrane. The ORFs for genes I and II overlap by eleven codons and the termination codon of gene II overlaps the initiation codon of gene III. Insertional inactivation experiments using integrational plasmids have indicated that the gerA locus is a single transcriptional unit. The expression of the gerA genes has been studied using a lacZ transcriptional fusion; they constitute a developmentally regulated operon. PMID- 3110008 TI - Complete nucleotide sequence of pTZ12, a chloramphenicol-resistance plasmid of Bacillus subtilis. AB - The complete nucleotide sequence of pTZ12, a chloramphenicol-resistance (CmR) plasmid (2517 bp) derived from Corynebacterium xerosis plasmid pTZ10, has been determined after propagation in Bacillus subtilis. The nucleotide sequence of pTZ12 suggests that a recombination event may have occurred naturally within the open reading frames for the Rep protein of pT181 (or a pT181-like plasmid) and pC221 (or a pC221-like plasmid). PMID- 3110009 TI - Cloning and nucleotide sequence of heavy- and light-chain cDNAs from a creatine kinase-specific monoclonal antibody. AB - Determination of creatine kinase isoenzymes by inhibition assay is a useful tool for the diagnosis and monitoring of myocardial infarction. We have established several mouse hybridoma lines secreting monoclonal antibodies with creatine kinase M-subunit inhibitory capacity. One of the monoclonal antibodies (MAK33) inhibits creatine kinase-MM by 80% without influencing the activity of creatine kinase-MB. A combination of two monoclonal antibodies increased the inhibition of creatine kinase MM up to 99.4%. Poly(A) + RNA of hybridoma cells secreting MAK33 was isolated and used for cloning cDNA of both heavy and light chains of this antibody. Full-length cDNA clones were obtained by hybridization with gamma 1 and kappa constant region cDNA probes. The complete nucleotide sequences from the variable regions including signal peptide and part of the 5'-untranslated regions have been determined. PMID- 3110010 TI - Reconstitution of functionally active antibody directed against creatine kinase from separately expressed heavy and light chains in non-lymphoid cells. AB - We report here for the first time reconstitution and secretion of functionally active antibody in non-lymphoid cells. Expression vectors for the light and the heavy chain of a monoclonal antibody directed against creatine kinase (EC 2.7.3.2) were introduced into COS and CHO Chinese hamster ovary dhfr- cells. Introduction of the expression vectors separately gave rise to immuno-reactive material in the culture supernatants, but only cotransfection of the expression plasmids resulted in secretion of protein with immuno-reactivity against antibodies directed against mouse heavy and light chains as well as specific antigen-binding affinity, as determined by enzyme-linked immunosorbent assay. Secreted kappa and gamma chains from reconstituted antibody were characterized by immunoadsorption and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In COS cells, reconstituted antibody was transiently secreted; cotransfection of kappa and gamma chain expression plasmids with a dihydrofolate reductase (DHFR) expression plasmid into CHO dhfr- cells gave rise to stable transformants secreting functionally active antibody. PMID- 3110011 TI - Transformation in Penicillium chrysogenum. AB - An auxotrophic mutant of Penicillium chrysogenum with a DNA rearrangement that affects the trpC region has been transformed to the Trp+ phenotype by using a plasmid that contains the trifunctional wild-type gene. A frequency of 40-80 transformants per microgram of input DNA was usually achieved. A low frequency of plasmid integration at the recipient mutated trpC gene was detected; however, most of the transformants integrated the plasmid DNA elsewhere into the genome. Some of the transformants contain multiple rearranged copies of the vector integrated in a tandem fashion. PMID- 3110012 TI - Sequence and genomic structure of ras homologues Dmras85D and Dmras64B of Drosophila melanogaster. AB - The ras homologues of Drosophila melanogaster located at 85D and 64B on the polytene chromosome map were cloned using the Ha-ras gene of Harvey murine sarcoma virus as a probe. The genomic sequences of Dmras85D and Dmras64B were determined and shown to differ from previously published sequences. Dmras85D is much more similar to the Ha-ras, Ki-ras, and N-ras genes than it is to either the Dmras64B gene or to the ras genes of Saccharomyces cerevisiae. Comparison of the Dmras85D genomic sequences with the previously published nucleotide sequence (Neuman-Silberberg et al., Cell 37 (1984) 1027-1033) shows that the positions of the two introns are not conserved relative to the positions of the introns in Dmras64B or in vertebrate ras genes. The Dmras64B and Dmras85D transcripts were analyzed by blot hybridization and shown to be dissimilar. The data suggest that the divergence of the Dmras genes was ancient, and that Dmras85D and Dmras64B have different functions. PMID- 3110013 TI - Multicopy expression vectors carrying the lac repressor gene for regulated high level expression of genes in Escherichia coli. AB - A series of new expression vectors (the pTTQ series) has been constructed for the regulated expression of genes in Escherichia coli. Based on the pUC plasmids, the pTTQ vectors contain a polylinker/lacZ alpha region flanked by the strong hybrid trp-lac (tac) promoter and the rrnB transcription terminator. Foreign genes can be inserted into the polylinker region of this expression cassette, to give either transcriptional or translational fusions within the lacZ alpha coding region. In most commonly used strains of E. coli, multiple copies of the lac operator titrate out the lac repressor. This phenomenon leads to significant expression from tac or lac promoters present on multicopy plasmids, even in the absence of inducers such as IPTG. To ensure maximal repression of the tac promoter on the pTTQ vectors in any host strain, the lacIQ allele of the lac repressor gene was added to the vectors. This makes them particularly useful for cloning genes when expression at high level is desired but is detrimental to cell growth. PMID- 3110014 TI - Characterization of human ferritin H chain synthetized in Escherichia coli. AB - We have inserted the coding region of the cDNA for human ferritin H chain into the expression vector pEMBLex2. The plasmid obtained is able to direct the synthesis of the ferritin H chain in Escherichia coli up to a concentration of 15% of total soluble proteins. All expressed subunits are found correctly assembled in the complete ferritin molecule, which can be easily purified. We have shown that the ferritin synthesized in E. coli has an Mr, electrophoretic mobility, and thermal stability similar to natural human isoferritins and is recognized by monoclonal antibodies specific for the H, but not by those for the L human ferritin chains. PMID- 3110015 TI - Parkinson's disease in the elderly: current management strategies. AB - Parkinson's disease generally responds well to dopaminergic therapy, but there is no unanimity concerning the optimal time for introducing dopaminergic medication. Dose-related side effects of these drugs may respond to a drug holiday, and fluctuations in response to levodopa may sometimes be helped by addition of bromocriptine to the drug regimen. Anticholinergic drugs, tricyclic compounds, and amantadine may sometimes lead to benefit, but any antiparkinsonian effect is often disappointing. Mental side effects may occur with all of the antiparkinsonian drugs, particularly the anticholinergic agents, and especially in the elderly. PMID- 3110016 TI - The aging thyroid in health and disease. AB - The most consistent biochemical thyroid abnormality associated with age, various illnesses, and drugs is the low T3 syndrome due to decreased activity of 5' deiodinase. Lower T3 levels may help reduce the catabolic effects of illness on the individual. The diagnosis of hypothyroidism can be missed in the elderly when its typical manifestations are attributed to aging. The diagnosis of hyperthyroidism in the elderly may likewise be difficult because of atypical clinical presentations. A high index of clinical suspicion should lead to a timely diagnosis of these eminently treatable disorders. PMID- 3110017 TI - Treating hyperlipidemia, Part III: Drug therapy. AB - In elderly patients at increased risk for cardiovascular disease due to lipid abnormalities, numerous medications are available for altering such abnormalities. Most of these drugs have side effects which, in the elderly, may necessitate lower dosing than usual. For persons with severe elevations of triglycerides, nicotinic acid (Niacin) and gemfibrozil (Lopid) may be used. For those who need a reduction in the LDL cholesterol, choices include bile acid binding resins, nicotinic acid, HMG CoA reductase inhibitors, probucol (Lorelco), and neomycin. PMID- 3110019 TI - Do you need a computer? Can you afford a computer? Part III. Making a computer a productive part of your office. PMID- 3110018 TI - [Metabolic reactions of representatives of different ethnic groups to a single use of ethanol]. PMID- 3110020 TI - Quantitative triple fluorochrome labeling study of lathyritic-rat mandible. AB - The present study was conducted to quantify the amount and distribution of new bone formation by triple fluorochrome labeling sequence in different areas of the mandibular bone of the control and lathyritic animals. The data was subjected to statistical analysis. Osteolathyrism significantly impaired the turnover and remodeling rates of periosteal and endosteal bone. The fluorescent bands were distinct and wider in the control than in the experimental animals. Mean ratio values for labeled bone showed considerable variations in different regions and age groups. The amount of labeled bone in the condyle and molar region of control animals was 1.49 to 1.77 and 1.41 to 1.78 times higher than in the lathyritic animals. PMID- 3110021 TI - Intravenous but not intragastric urogastrone-EGF is trophic to the intestine of parenterally fed rats. AB - The effects of beta-urogastrone/human epidermal growth factor (URO-EGF) on intestinal epithelial cell proliferation were studied in rats in which intestinal cell proliferation had been reduced to a steady state basal level, by maintaining the rats on total parenteral nutrition. The accumulation of arrested metaphases over a two hour time period was determined in a dose response study. Increasing doses of URO-EGF progressively raised the two hour collection of metaphases and intestinal weights. Intravenous infusion of URO-EGF was also effective in restoring cell proliferation when it was infused after the intestine had become hypoproliferative. beta-urogastrone/human epidermal growth factor administered through an intragastric cannulae thrice daily had no significant effect on intestinal weight or crypt cell production rate or metaphase collection. It is proposed that one of the in vivo actions of urogastrone-epidermal growth factor is the maintenance of gastrointestinal growth and that this occurs through a systemic rather than a luminal mechanism. PMID- 3110022 TI - Protein losing enteropathy: an unusual presentation of intestinal schistosomiasis. AB - A patient presenting with features suggestive of malabsorption syndrome is described who had florid intestinal schistosomiasis on peroral biopsy of the jejunum. Liver biopsy and rectal biopsy also revealed schistosomal ova. Biochemical studies revealed severe hypoproteinaemia and hypoalbuminaemia, caused by a protein losing enteropathy. This is the first reported case of protein losing enteropathy caused by intestinal schistosomiasis. PMID- 3110023 TI - Effect of antepartum ritodrine on the cardiorespiratory status of the newborn after elective cesarean section. AB - Heart rate (HR), heart rate variability (HRV), respiratory rate (RR) and transcutaneous PO2 and CO2 of 12 infants born by elective cesarean section were monitored during the first postnatal hour in order to evaluate the effect of the beta-mimetic tocolytic drug ritodrine. Six of the mothers received ritodrine by infusion and the other 6 physiological saline during the 2 h prepartum. The Apgar scores of the treatment group were higher (p less than 0.05) but there was a significant increase in RR (p less than 0.05) during the first hour in these babies. Arterial blood pressure (BP) was lower in the group whose mothers had received ritodrine (p less than 0.05) but there was no difference in pulse pressure. Transcutaneous pressure of CO2 (PtcCO2) of the controls decreased during the first hour (p less than 0.05). Transcutaneous pressure of O2 (PtcO2) increased during the first postnatal hour (p less than 0.01) when both groups were examined together. HR of both groups was relatively high and HRV low. PMID- 3110024 TI - Spectrophotometric method for the assay of human blood coagulation factor VIII. AB - A spectrophotometric method for the assay of human blood coagulation factor VIII in plasma is presented. The chromogenic assay for factor VIII:C in plasma is performed in 3 steps: activation of factor VIII by thrombin; activation of factor X in a mixture of factor X, factor IXa, phospholipids/Ca2+ and plasma containing activated factor VIII, and determination of the rate of factor Xa formation with the chromogenic substrate S2337. Within-assay variation was between 5 and 6.9% for factor VIII:C activities between 20 and 150%. Clotting and chromogenic factor VIII:C activities were compared in plasma of 50 normal healthy donors (coefficient of correlation r = 0.83). PMID- 3110025 TI - Effect of single-dose aspirin on TXA2 and PGI2 cyclooxygenases in vivo. AB - The present study investigated the sensitivities of the thromboxane A2 (TXA2) cyclooxygenase and the prostacyclin (PGI2) cyclooxygenase to aspirin using an in vivo animal model. In this model, arachidonic acid (AA) was administered to mice via cardiac puncture, and plasma levels of thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) were determined. Infusion of AA (5, 10, 25 and 50 mg/kg) resulted in a dose-dependent increase in both TXB2 and 6 keto PGF1 alpha. Pretreatment with aspirin resulted in a dose-dependent and parallel decrease in TXB2 and 6-keto PGF1 alpha production. This nonselective inhibition occurred at all doses of aspirin (1, 10 and 50 mg/kg) and at all levels of cyclooxygenase activity (5-50 mg/kg AA). These results indicate that the TXA2 and PGI2 cyclooxygenase enzymes are equally sensitive to inhibition by a single dose of aspirin. PMID- 3110027 TI - Spinal fluid procoagulant activity in leukaemic patients treated with intrathecal methotrexate. AB - A procoagulant activity was found in cerebrospinal fluid (CSF) of patients with myelo- or lymphoproliferative diseases on intrathecal therapy with methotrexate, independently of leukaemic CNS involvement. This activity did not correlate with the cell count in CSF and disappeared on storage at -40 degrees C or after filtration with 0.22 nm filters. Dosage of coagulation factors revealed a strong increase in Factor V activity (F. V:C), an increase in Factor VIII procoagulant activity (F. VIII:C) without a correspondent increase in Factor VIII related antigen (F. VIII R:Ag), and an inconstant increase in Factor IX activity (F. IX:C). These activities all disappeared after filtration with 0.22 micron filters but not with 1.2 micron filters. It is concluded that complexes formed by membrane phospholipids and Factor V were responsible for the procoagulant activity lost after storage. The F. VIII and F. IX.-like procoagulant activity was not lost after storage; it was considered unspecific and attributed to thromboplastin-like substances. PMID- 3110028 TI - Respiratory syncytial virus infection in hospitalized children over one year of age. PMID- 3110029 TI - A phase-polycardiographic and apex cardiographic appraisal of the effect of treatment of left ventricular disorders in patients with chronic renal failure. PMID- 3110026 TI - Influence of heparin, aspirin, streptokinase and factor VIII (AHF) on amorphous electron-dense substance, a mediator of platelet and thrombus adhesion in vivo. AB - Platelet adherence and aggregation on vessel walls are the first crucial steps in thrombogenesis and atherosclerosis. Whether platelets can be activated on damaged endothelial cells or their activation is achieved only when subendothelial structures are exposed was controversially discussed in the past. Recently, an electron-microscopic study has revealed an amorphous electron-dense substance (AEDS) after endothelial cell damage and has discussed its role as a possible trigger of thrombogenesis. The aim of the present study is to elucidate the role and origin of this substance and to investigate the influence which inhibitors of platelet function (acetylsalicylic acid), coagulation (heparin), stimulation of fibrinolysis (streptokinase) and addition of factor VIII (AHF) have on AEDS. PMID- 3110030 TI - On the problem of hereditary predisposition in gastric ulcer disease. PMID- 3110032 TI - Determining the type of prostaglandins excreted from the smooth muscles under the influence of the activating serum factor in women with pathological pregnancy. PMID- 3110031 TI - The effect of a stimulatory enterocytogenin (SEG) on the growth of growing rats. PMID- 3110033 TI - Investigation of pregnancy-specific beta 1-glycoprotein (SP1) in the serum of healthy non-pregnant women. PMID- 3110034 TI - Changes in the activity of lactatedehydrogenase, malatdehydrogenase, alkaline and acid phosphatase in the saliva of anesthesiological personnel. PMID- 3110035 TI - A study of the possibilities for using oils of fir, dwarf-pine, white pine and black pine as plasticisers for root-filling materials. PMID- 3110036 TI - Some specific aspects of insulin secretion in obese subjects with familial predisposition to diabetes. PMID- 3110037 TI - Detection of drug residues on the hands of subjects by surface sampling and ion mobility spectrometry. AB - This paper deals with the detection of drug residues on the hands of human subjects. The results demonstrate that detectable amounts of particulate matter are transferred to the hands by brief contact with drug tablets. A sampling and analysis method has been developed, and is based on the aspirating and trapping of drug microparticles on a filter plug, to be followed by thermal desorption directly into an ion mobility spectrometer. The technique is suited for initial field screening in clinical and forensic applications. The major drugs detected were diazepam, amitriptyline, codeine, acetaminophen, nitroglycerin, and delta 9 tetrahydrocannabinol (delta 9-THC). PMID- 3110038 TI - [Islet cell transplantation and diabetes mellitus]. PMID- 3110039 TI - [Lithium prevention of depression 100 years ago--an ingenious misconception]. AB - The rediscovery of C. Lange's book "Uber periodische Depressionszustande und ihre Pathogenesis auf dem Boden der harnsauren Diathese", Copenhagen 1886, in a German translation by H. Kurella in 1896, gave rise to appreciate its value, to make its misconception intelligible, and to write down the author's and the translator's course of life. In his booklet Carl Lange gives a specification of depression in a most modern form. It is thrilling to read his report on about 2000 depressed out-patients successfully treated over a 20-year-period - from today's point of view lege artis - with lithium carbonate as a long-term-prophylaxis for recurrent depression. His intricate misconception is based upon his therapeutic orientation of treating gout and "uric acid diathesis", respectively. This conception of depression as "brain gout", part of an inflationary enlarged pathogenesis of numerous internal, neurological, and other diseases, had been set up by Garrod. "Brain gout" was a curiosity in the established psychiatry and disappeared from scientific thinking with a new medical knowledge of gout and rheumatism. With that, of course, the pioneering knowledge of the effectiveness of lithium disappeared too. PMID- 3110041 TI - Clinical usefulness and limitations of serum thyrotropin measurement by 'ultrasensitive' methods. Comparisons of five kits. AB - Five different ultrasensitive thyrotropin (TSH) assay kits (Boots-Celltech, Immunotech, ORIS-CIS, Travenol and Boehringer) have been used for TSH measurements in various conditions. All the kits were based on an immunometric method but differed with regard to components and procedure. The sensitivity appeared essentially the same for the five kits (0.10 microU/ml) as well as the intraassay precision (coefficient of variation less than 12%). In contrast, the interassay coefficients of variation in the low TSH range varied from 12.8 to 21.3%. Discrepancies from kit to kit were observed and accounted for by differences in the components and procedure of the kits. Basal serum TSH was determined in normal subjects (n = 261) and in patients with thyroid dysfunction (n = 392). No overlap was shown between normals and patients with overt hypothyroidism. In contrast, an overlap existed between normals and hyperthyroids for all the kits but one. Measurements in patients with nontoxic goiter showed that TSH may be undetectable in clinically euthyroid patients, whatever the kit used. After TRH stimulation, 95% of the 375 patients tested associated either an absence of response to TRH with undetectable basal TSH values, or a blunted response with low basal TSH levels or normal response with normal basal TSH concentrations. However, 9 patients with suppressed TSH showed a response to TRH and 7 patients with normal basal TSH levels presented an exaggerated response to TRH. Taken together, these results demonstrate that even though ultrasensitive measurements of TSH do not meet the expectation of completely discriminating euthyroid from hyperthyroid patients, ultrasensitive TSH assay kits represent a powerful tool in the diagnosis of thyroid dysfunction, which would eliminate, in most instances, the need for TRH test and diminish thyroid hormone assay requests. PMID- 3110040 TI - Prevention of acute gastric mucosal lesions by Solcoseryl. AB - Solcoseryl, a deproteinized extract from calf blood containing various biologically active substances, has been reported to promote the healing of skin wounds and gastric ulceration In this study, the gastroprotective effects of Solcoseryl vis-a-vis acute gastric mucosal damage were examined in rats. Solcoseryl significantly reduced the formation of acute lesions induced by intragastric application of absolute ethanol or acidified taurocholate and by water immersion and restraint stress, but failed to affect those caused by acidified aspirin. Since Solcoseryl did not offer protection in the absence of mucosal prostaglandins (PG) e.g. in aspirin-induced gastric damage, it is likely that PG may be involved in the observed gastroprotective activity of the drug. Solcoseryl failed to affect gastric acid or pepsin secretion, but increased mucosal blood flow. Thus PG generated by Solcoseryl might contribute to the maintenance of the observed mucosal microcirculation and the prevention of lesion formation by corrosive substances and stress conditions. PMID- 3110043 TI - The impact of cost containment on alcohol and drug treatment. AB - Hospitals offering alcohol and drug treatment programs that meet certain criteria are currently exempt from Medicare's prospective payment system, which was introduced in October 1983 as a means of containing medical costs. Substance abuse experts have successfully lobbied for changes in the alcohol and drug diagnosis-related groups (DRGs) on which reimbursement is based so that they now more accurately reflect patterns of inpatient detoxification and rehabilitation. However, major adjustments are still necessary to protect the quality of care and financial diversity of substance abuse treatment programs. Differences in types of treatment facilities must be considered in order to prevent a major redistribution of funds away from facilities offering specialized care. Incentives to reduce costs must be balanced with a determination to maintain high quality care. PMID- 3110042 TI - High voltage orbital radiotherapy and surgical orbital decompression in the management of Graves' ophthalmopathy. AB - We report on 2 groups of patients with Graves' ophthalmopathy. A group of 21 patients was treated by high voltage (18 MV) orbital radiotherapy combined with mean doses of corticoids. The results were good or excellent in 12 patients (mean score 6.62 before and 4.0 after, soft tissues greater than proptosis greater than extraocular muscle involvement), without any complications from irradiation. Patients undergoing surgery initially presented less severe symptoms, even 7 patients treated after corticoid and/or radiotherapy failure. The results were satisfactory in all patients (mean score 5.1 before and 2.4 after, proptosis greater than soft tissues greater than extraocular muscle involvement). Both methods showed results within 3 months, and they can be combined. PMID- 3110044 TI - Life Care at Home plan ready for 1988 start-up. PMID- 3110046 TI - CHAMPUS plans Oct. 1 start-up of DRG system. PMID- 3110045 TI - On Lok: replicating a capitated LTC program. PMID- 3110047 TI - AVGs (ambulatory visit groups): will insurance firms follow the leader? PMID- 3110048 TI - Migration and changes in ABO and Rh blood group clines in Britain. PMID- 3110050 TI - L-ornithine and L-lysine need their alpha-carboxyl groups for effective inhibition of bovine liver arginase. PMID- 3110051 TI - [Effect of factor VIII, factor IX and immunoglobulin preparations on mitogen induced lymphocyte proliferation]. AB - The influence of therapeutic dosages of factor VIII, factor IX and immunoglobulin preparations on the proliferative capacity of mitogen-activated lymphocytes from patients with hemophilia or idiopathic thrombocytopenia was investigated. Addition of protein preparations in vitro led to inhibition of lymphocyte proliferation, predominantly with the mitogen staphylococcus enterotoxin B. After intravenous application of proteins also stimulatory effects were seen. Since long-term treatment with protein preparations might impair immune functions, their application should be considered carefully. PMID- 3110049 TI - Monoclonal antibody modification with chelate-linked high-molecular-weight polymers: major increases in polyvalent cation binding without loss of antigen binding. AB - Polyethyleneimine or polylysines of differing molecular sizes were substituted with either EDTA or DTPA and then with succinic acid groups. These polymers were then reacted with the amino groups on myosin-specific monoclonal antibody or its Fab using a water soluble carbodiimide. The polymer-antibody complexes were capable of binding up to 150 di- or trivalent ions per mole (Mn++, Gd , or 111In ) without attendant loss of antigen binding. The polylysine derivatives of the intact antibody were rapidly cleared and sequestered in the liver, whereas the polylysine 14-kilodalton (kd) derivative of Fab was cleared from the circulation with minimal hepatic and kidney sequestration. This differed from the biodistribution of intact antimyosin or its Fab labeled with 111In via direct attachment of DTPA to the epsilon amino group of the lysyl residues. Applications in magnetic resonance and nuclear imaging are envisioned. PMID- 3110052 TI - Transcriptional control of mu- and kappa-gene expression in resting and bacterial lipopolysaccharide-activated normal B cells. AB - When murine resting B cells are polyclonally stimulated by bacterial lipopolysaccharide (LPS) in vitro for a short period of 4 days, they are activated to DNA synthesis and cell division, and they also differentiate to immunoglobulin (Ig)-secreting plasma cells. These two events are accompanied with several qualitative changes at the Ig mRNA level: the disappearance of delta mRNA after stimulation, the switch from membrane to secretory form of mu-mRNA, and the late appearance of IgM joining chain (J-chain) mRNA. There is also a quantitative increase of Ig-gene expression at the level of: Ig gene transcription, mu-, kappa and J-chain mRNA accumulation, and Ig translation and secretion. A comparison of Ig transcription rates before and in the course of LPS stimulation, as determined by in vitro transcriptional run-on assays, has shown that there is a large increase of the RNA polymerase density on both mu- and kappa-loci (30-60-fold), which is quantitatively comparable with the accumulation of both mu- and kappa mRNAs at the steady state mRNA level. These data therefore suggest that former results obtained with tumor cells regarding post-transcriptional control of Ig gene expression do not reflect the physiological behavior of normal B cells with respect to the molecular events of B cell triggering. We also propose that additional molecular events such as RNA processing and the transcriptional activation of J-chain gene might be essential for controlling the maximal transcriptional rate across the Ig loci. PMID- 3110053 TI - Differential effects of beta- and gamma-interferons on natural killer cell mediated lysis of lung carcinoma cells. AB - Peripheral blood lymphocytes from healthy donors (PBL) poorly lyse lung carcinoma cell lines A-549, A-427 and SK- MES-1 when tested in a short-term chromium release assay. When PBL are preincubated with human beta-interferon (IFN-beta), these cell lines are lysed with an efficacy comparable to that of erythroleukemia K-562 cells, the standard targets used in natural killer cell assays. However, when PBL are preincubated with gamma-interferon (IFN-gamma) instead, lysis of the lung carcinoma lines is little augmented. Unlabeled lung carcinoma A-549 cells block chromium release from labeled K-562 cells with non-boosted and IFN-gamma or IFN-beta-boosted effector cells. Also with the IFN-beta treated effectors, chromium release from A-549 targets is inhibited by unlabeled K-562 cells. Therefore, cells that lyse K-562 cells must be able to recognize A-549 cells, and, in the case of IFN-beta pretreated effectors, cause the killing of these cells as well. Data obtained with effector cells separated on discontinuous Percoll gradients also indicate that the same cells that lyse A-549 cells are responsible for lysis of K-562 cells. We conclude that in response to IFN-beta, effector cells previously able to lyse K-562, but unable to lyse A-549 targets, mature into fully competent killer cells capable of lysing tumor cells from lymphoid as well as from lung cancer origin. This effect is not elicited by IFN gamma, indicating that killer cells respond differently to both interferon types. PMID- 3110055 TI - [Ichthyosis linearis circumflexa. Description of 2 clinical cases]. PMID- 3110056 TI - Histopathological and bacteriological status of quiescent cases of pulmonary tuberculosis. PMID- 3110054 TI - Rapid intracellular calcium changes in U937 monocyte cell line: transient increases in response to platelet-activating factor and chemotactic peptide but not interferon-gamma or lipopolysaccharide. AB - The dye fura-2, a potentially more sensitive successor to quin2 for measuring intracellular free calcium ion concentrations [(Ca2+]i), has been applied here to investigate the possible involvement of early changes in [Ca2+]i in the stimulation of the human monocyte-macrophage-like cell line U937. The calcium ionophores A23187 and ionomycin, known pharmacological stimuli for macrophages, were found to cause sharp rises in [Ca2+]i as expected. Responses analogous to those reported for a murine macrophage cell (J774) were obtained on stimulation of U937 cells with ATP which caused rapid, but transient, increases in [Ca2+]i (from resting levels of about 70 nM to peaks of about 200 mM). In addition to ATP, several agents known to activate macrophages were used as stimuli. In particular, platelet-activating factor (PAF; 1-0-alkyl-2-acetyl-sn-glycero-3 phosphocholine) was found to cause rapid, but transient, increases in [Ca2+]i (from resting levels of about 70 nM to peaks of about 400 nM) even at concentrations as low as 10(-10) M. This contrasts with responses to ATP that were markedly reduced at 10(-6) M compared with 10(-5) M or above, suggesting that PAF is a highly potent stimulus for intracellular calcium mobilization in macrophages. Similar responses were obtained with chemotactic peptide (N-formyl methionyl-leucyl-phenylalanine). On the other hand, two agents known to be potent activators of macrophages, interferon gamma and lipopolysaccharide, had no rapid effect on [Ca2+]i. This may reflect differences in the kinetics of signal response coupling or alternatively a different mechanism of action by-passing the need for rapid elevation of [Ca2+]i. PMID- 3110057 TI - Alteration in the levels of serum lipid peroxide, cyclooxygenase activity and free fatty acids in bronchial asthma. PMID- 3110058 TI - Serology of tuberculosis. PMID- 3110059 TI - Hormonal & H-Y antigen studies in 49, XXXXY syndrome. PMID- 3110060 TI - The susceptibility of three species in three genera of mosquito larvae to a microsporidian Vavraia culicis (Weiser) and its histopathology on the tissues of the recipient host Anopheles gambiae Giles in the laboratory. PMID- 3110061 TI - Hexachlorobenzene residues in selected species of land and sea birds in northern Germany. AB - High residues of hexachlorobenzene (HCB) occurred in sea-bird eggs from the banks of the river Elbe, decreasing to the north in areas influenced by the running tide. The residues of polychlorinated biphenyls (PCB) and of dichlorodiphenyl trichloroethane including its metabolites were more evenly distributed. In rooks the residues of chlorinated pesticides and PCB were dependent on the land use of the regions compared (e.g., industrial, agricultural), but no such correlation was found for the HCB residues. There was still a significant difference between the HCB residues of sparrows living in small towns and those of agricultural areas. Another source of HCB residues may be the wood preservatives; HCB contamination of two species of birds found near sawmills was greater than for birds of the same species found elsewhere. PMID- 3110062 TI - Effects of ethylenediaminetetracetic acid on hexachlorobenzene-induced changes in rats. PMID- 3110063 TI - Porphyria turcica: hexachlorobenzene-induced porphyria. Neurological manifestations and therapeutic trials of ethylenediaminetetracetic acid in the acute syndrome. PMID- 3110064 TI - Reduction of the human body burdens of hexachlorobenzene and polychlorinated biphenyls. AB - Adipose-tissue concentrations of hexachlorobenzene (HCB), four other pesticides and 10 polychlorinated biphenyl congeners were significantly reduced by enhanced mobilization and excretion through the method developed by Hubbard. Electrical workers paired by age, sex and potential for polychlorinated biphenyl exposure were divided into treatment and control groups. Adipose-tissue concentrations were determined pre- and post-treatment, and 3 months post-treatment. Daily treatment was provided for 3 weeks, consisting of heat stress and niacin administration to enhance mobilization and polyunsaturated-oil administration to enhance excretion, with other components administered to provide protection from mobilized chemicals. Adjusted for re-exposure as represented in the control group, HCB body burdens were reduced by 30% at post-treatment and 28% 3 months post-treatment. Mean reduction of polychlorinated biphenyl congeners was 16% at post-treatment and 14% 3 months post-treatment. Analysis of variance indicates these reductions are statistically significant (f less than 0.001). Enhanced excretion appeared to keep pace with mobilization, as blood-serum levels in the treatment group did not increase during treatment. Post-treatment remission of symptoms associated with chemical exposure has been summarized according to reports from related studies. PMID- 3110065 TI - Vaccine potential of Pseudomonas aeruginosa O-polysaccharide-toxin A conjugates. AB - Serologically reactive O-polysaccharide from nine serotypes of Pseudomonas aeruginosa were covalently linked to toxin A via reductive amination, with adipic acid dihydrazide serving as a spacer molecule. The conjugates were composed of toxin A/O-polysaccharide ratios ranging from 1.17:1 to 3:1. All possessed an average Mr of greater than 10(6), were devoid of ADP ribosyltransferase activity associated with toxin A, and were nontoxic for mice and guinea pigs. The conjugates were stable from toxic reversion when stored at 37 degrees C for 28 days. The conjugation condition used preserved a substantial proportion of critical epitopes on the toxin A molecule as shown by the ability of toxin A neutralizing monoclonal antibodies to react with the various conjugates. All nine conjugates were capable of evoking an antitoxin A and an antilipopolysaccharide immunoglobulin G (IgG) response in mice and rabbits. Rabbit antitoxin A IgG was capable of neutralizing the cytotoxic effect of toxin A, whereas mice immunized with any of the conjugates were protected against toxin A intoxication. Rabbit anti-conjugate IgG, when passively transferred to mice, was highly effective at preventing fatal P. aeruginosa burn wound sepsis. PMID- 3110067 TI - Purification, characterization, and toxicity of the sulfhydryl-activated hemolysin listeriolysin O from Listeria monocytogenes. AB - We purified and characterized an extracellular hemolysin produced by Listeria monocytogenes. Hemolysin production was greatly enhanced by growing bacteria in resin (Chelex)-treated medium. This hemolysin was separated as a homogeneous protein of 60,000 daltons by using thiol-disulfide exchange affinity chromatography. This protein was a sulfhydryl-activated toxin, termed listeriolysin O, which shared the classical properties of other bacterial sulfhydryl-activated toxins: inhibition by very low amounts of cholesterol; activation by reducing agents and suppression of the lytic activity by oxidation; antigenic cross-reactivity with streptolysin O. However, listeriolysin O differed remarkably from the other sulfhydryl-activated toxins in that its cytolytic activity towards erythrocytes from various animal species was maximum at low pH (approximately 5.5) and was undetectable at pH 7.0. This suggests that the lytic activity of the toxin in host tissues might be better expressed in the acidic microenvironment, including macrophage phagosomes where bacteria presumably replicate. Listeriolysin O was lethal to mice (50% lethal dose of ca. 0.8 microgram) and induced a rapid inflammatory reaction when injected intradermally. These results favor the view that listeriolysin O might play a major role during intracellular replication of L. monocytogenes, ultimately promoting death of infected macrophages. PMID- 3110066 TI - Serotype specificity and immunogenicity of the capsular polymer of Haemophilus pleuropneumoniae serotype 5. AB - Serotyping of Haemophilus pleuropneumoniae and serologic assays for detection of serotype-specific antibody are problematic due to the potential cross-reactivity of the crude antigens used for raising immune serum or for serology. The capsular polymer (CP) of H. pleuropneumoniae serotype 5 was investigated for serotype specific activity with antiserum to whole cells or with antiserum made monospecific to CP by adsorption with a capsule-deficient mutant. When antiserum to whole cells or monospecific antiserum to CP was tested against purified CP from serotypes 1 to 7 by immunodiffusion or enzyme-linked immunosorbent assay, only capsules of serotype 5 were reactive. In addition, only encapsulated serotype 5 cells reacted with serum monospecific to CP in an indirect immunofluorescent-antibody assay. Serotype-specific antibody was completely inhibited in each assay by preincubation of purified CP with the serum. Antiserum to whole cells of H. pleuropneumoniae serotype 5 contained antibodies to proteins and lipopolysaccharide; these antibodies cross-reacted with antigens of heterologous serotypes by dot-blot enzyme-linked immunosorbent assay and immunoblotting. The antigenic activity of CP was stable after heating for at least 30 min at 100 degrees C. High titers of antibody to CP were present in the sera of rabbits immunized intravenously with whole log-phase cells or in the convalescent sera of pigs experimentally infected with H. pleuropneumoniae serotype 5. However, the purified CP was poorly immunogenic in rabbits and swine. Our results indicate that the capsule is the serotype-specific antigen of H. pleuropneumoniae and that a monospecific antiserum to capsule or purified capsule should be used for serotyping or serologic assays, respectively. PMID- 3110068 TI - Expression of a mutant, full-length form of diphtheria toxin in Escherichia coli. AB - A mutant, full-length form of diphtheria toxin was cloned into Escherichia coli K 12 and expressed under BL-1 + EK-1 containment. A gene fragment encoding the catalytic domain of the toxin was subjected to oligonucleotide-directed mutagenesis to produce a three-base mutation of an active site residue; Glu-148 was thereby replaced by Ser. Ser-148 fragment A had less than 1% of the ADP ribosyltransferase activity of wild-type fragment A. Next, the complementary portion of the toxin structural gene was spliced with the mutated DNA fragment downstream of codon 148 to produce a construct that encoded mutant whole toxin with Ser at position 148. The mutant toxin was indistinguishable from authentic diphtheria toxin by Western blot analysis, but was about 800-fold less cytotoxic than wild-type toxin for BS-C-1 cells. Evidence from subunit exchange experiments indicated that a substantial fraction of the mutant toxin contained a fully functional B moiety, capable of mediating the entry of wild-type fragment A into sensitive mammalian cells. This combination of approaches provides a means of applying recombinant DNA methods in E. coli to study structure-function relationships in whole diphtheria toxin. PMID- 3110069 TI - Immunosuppressive effect of cyclosporin A on Mycobacterium bovis BCG infections in mice. AB - The effect of increasing doses of cyclosporin A (CsA) given to mice infected intravenously with Mycobacterium bovis BCG was investigated. Development of both tuberculin hypersensitivity and acquired antituberculous resistance was suppressed in a dose-responsive manner. Daily dosages at 100 mg/kg of body weight prevented any reduction in the BCG counts within the lungs, liver, or spleen. This effect was associated with lowered nonspecific resistance to a Listeria monocytogenes challenge and a decline in specific protective immunity adoptively transferred to naive recipients. CsA treatment had no effect on antilisterial activity by activated macrophages or on the antituberculous immunity expressed by specific memory T cells. CsA treatment inhibited the ability of BCG-vaccinated mice to produce gamma interferon (IFN-gamma) after a secondary stimulation with live BCG or with lipopolysaccharide. Spleen cells from BCG-infected mice which were exposed to daily treatment with CsA showed reduced IFN-gamma production in response to purified protein derivative or concanavalin A stimulation, suggesting that the immunosuppressive effect of CsA on BCG-infected mice was expressed by inhibiting the development of effector T cells responsible for the production of IFN-gamma. PMID- 3110071 TI - Recurrent erysipelas: predisposing factors and costs of prophylaxis. AB - After an average follow-up time of three years, recurrent erysipelas was observed in 29% of 143 patients admitted primarily with erysipelas. Nineteen patients (13%) had two or more recurrences during this period. The predisposing factor with the highest recurrence rate was venous insufficiency. Regular prophylaxis with phenoxymethylpenicillin (or erythromycin in penicillin allergics) after the second recurrence may be cost-effective. This antibiotic prophylaxis is only recommended in patients with predisposing factors who have suffered severe attacks. PMID- 3110070 TI - In vivo studies with two phospholipase C fractions from Pseudomonas aeruginosa. AB - Two phospholipase C fractions were detected in culture supernatants from Pseudomonas aeruginosa ATCC 19660, PAO1, and D10C by preparative polyacrylamide gel electrophoresis. Both hemolytic fractions from strain ATCC 19660 were isolated by polyacrylamide gel electrophoresis and were found to cause paralysis, death, dermonecrosis, footpad swelling, and vascular permeability in mice. In vivo toxicity was directly associated with enzymatic activity. PMID- 3110072 TI - Meningococcal pericarditis in the absence of meningitis. AB - A 16 year-old female presented with cardiac tamponade due to purulent meningococcal pericarditis without concomitant meningitis or meningococcaemia. She recovered after aspiration of the pericardial effusion and administration of a high dose of benzylpenicillin via a continuous infusion. PMID- 3110073 TI - Synergistic enhancement of mitogen responses of human lymphocytes by inhibitors of cyclo-oxygenase and 5,8,11-eicosatriynoic acid, an inhibitor of 12 lipoxygenase and leukotriene biosynthesis. AB - Blood mononuclear cells are well-known producers of various cyclo-oxygenase and lipoxygenase metabolites of arachidonic acid, some of which possess immunoregulatory functions. In the present investigation, we have examined 3H thymidine incorporation in human blood lymphocytes cultured with polyclonal mitogens and antigens in the presence of various inhibitors of cyclo-oxygenase (such as indomethacin and meclofenamic acid) and an inhibitor of 12-lipoxygenase and leukotriene biosynthesis, 5,8,11-eicosatriynoic acid (ETI). It was observed that these inhibitors could augment mitogen responses of nonpurified lymphocyte preparations but not of preparations which were depleted of monocytes. The results indicate that monocytes and not lymphocytes were the main producers of immunosuppressive eicosanoids derived from arachidonic acid. Further, mitogenic responses in the presence of both an inhibitor of cyclo-oxygenase and ETI were augmented to a higher extent than expected. Again, this enhancement was not observed in preparations depleted of monocytes. Arachidonic acid metabolism was examined in mitogen-stimulated cultures pulsed with 14C-arachidonic acid. It was observed that the production of three metabolites was inhibited by meclofenamic acid, whereas the amounts of another 14Cr-labeled compound were almost doubled in the presence of meclofenamic acid. PMID- 3110074 TI - Cell-mediated immunity and biological response modifiers in insulin-dependent diabetes mellitus complicated by end-stage renal disease. AB - Previous studies have shown several immunoregulatory abnormalities in insulin dependent diabetes mellitus (IDDM). In this report we compared peripheral blood mononuclear cells (PBMC) from patients with IDDM complicated by end-stage renal disease (ESRD) to those from normal subjects and from patients with ESRD of different etiologies for their: natural killer (NK) and antibody-dependent cell mediated cytotoxic (ADCC) activities; modulation of NK and ADCC activities by biological response modifiers (BRM) including purified human lymphoblastoid interferon, human recombinant alpha-2 interferon, human gamma interferon and human recombinant interleukin 2; proliferative response of T and B lymphocytes to concanavalin A (Con A), phytohemagglutinin and pokeweed mitogen, and ability to produce T-cell growth factor (interleukin 2; IL-2). PBMC of diabetic patients demonstrated significantly lower NK activity than normal and ESRD subjects. Upon treatment with BRM, NK activity was augmented and achieved normal levels. ADCC activity was not different from that of normal controls and exhibited similar increases when stimulated by BRM. The proliferative responses to Con A, phytohemagglutinin and pokeweed mitogen as well as IL-2 production in response to Con A stimulation were significantly lower in the IDDM group. Our results indicated that NK cells from patients with IDDM can respond to IL-2 with enhanced cytotoxicity, and, because activation of resting T cells by mitogenic stimuli depends on the production of IL-2 as well as the appearance of a receptor for IL 2, our finding of low levels of in vitro IL-2 production by PBMC from patients with IDDM may explain the depressed NK activity and the observed poor response to T-cell mitogens. PMID- 3110075 TI - Eosinophil chemotactic lymphokine produced by spleen cells of Schistosoma japonicum-infected mice. II. Physicochemical heterogeneity of eosinophil chemotactic lymphokines selective to bone marrow- or peritoneal exudate eosinophils. AB - The physicochemical nature of eosinophil chemotactic factor (ECF) was examined by using different maturation stages of eosinophils, namely eosinophils obtained from bone marrow (BM-Eo) and those obtained from peritoneal cavity (PEC-Eo), as the indicator of in vitro chemotaxis. As the ECF source, the conditioned medium of the culture of spleen cells obtained from Schistosoma japonicum-infected mice was used. When the conditioned medium was chromatographed by Sephadex G75, apparent molecular weight of ECF activity against BM-Eo was 15,000, whereas that against PEC-Eo was 30,000. Similar results were obtained when the conditioned medium was chromatographed by high-pressure liquid chromatography using SW3000 column. After NaCl-linear gradient elution of DE52 anion-exchange chromatography of the conditioned medium, ECF activity against PEC-Eo was detected at the 0.1 M NaCl region of the gradient, whereas that against BM-Eo was detected at around the 0.14 M NaCl region. After isoelectric focusing, however, ECF activity against BM-Eo and PEC-Eo was detected at the same position, approximately pH 3.6. The results of surface phenotype analysis show that the cells responsible for the production of two types of ECF lymphokines are both Thy-1.2+, Lyt-1.2-, Lyt-2.2+. When ECF activity in the conditioned medium of antigen-specific T cell clones was examined, 6 out of 7 clones produce ECF lymphokine relatively selective to PEC Eo, whereas one clone produce ECF lymphokine relatively selective to BM-Eo. These results suggest that physicochemically different ECF lymphokines selective to different maturation stages of eosinophils are involved in the mediation of eosinophilia. PMID- 3110076 TI - Plasma flecainide concentrations following acute myocardial infarction. AB - Plasma flecainide concentrations were measured in 10 patients with acute myocardial infarction. Following an oral loading dose of 300 mg plasma concentrations were highly variable and unpredictable. Subsequently, doses of 150 mg twice daily produced mean plasma flecainide concentrations consistently above 400 micrograms/1 within 48 hours. Oral flecainide is, therefore, subject to the same problems of varying oral bioavailability as other antiarrhythmic drugs tested following acute myocardial infarction and, initially, an intravenous regime remains preferable. Mild pulmonary oedema occurred in six patients and, although it responded to one dose of frusemide and did not recur, flecainide must be used with caution when significant left ventricular dysfunction is suspected. PMID- 3110077 TI - Gonorrhea and the story of resistant Neisseria gonorrhoeae. PMID- 3110078 TI - Method for the determination of three toxic non-ortho chlorine substituted coplanar PCBs in environmental samples at part-per-trillion levels. AB - A method has been devised combining alkali digestion, carbon chromatography and high-resolution gas chromatography for the determination of 3,3',4,4'-tetra, 3,3',4,4',5-penta, and 3,3',4,4',5,5'-hexachlorobiphenyl, the biologically active congeners of PCBs and approximate isostereomers of 2,3,7,8-TCDD. This method permits determinations of parts-per-trillion levels of these toxic residues in biological samples. Interference both from biogenic and from xenobiotic substances was reduced to extremely low levels. Using this method, 13.5 ng of 3,3'4,4'-tetrachlorobiphenyl/g, 0.89 ng of 3,3'4,4',5-pentachlorobiphenyl/g and 0.64 ng of 3,3',4,4'5,5'-hexachlorobiphenyl/g were detected on wet weight basis in the blubber of a finless porpoise. To our knowledge this is the first report on the three toxic non-ortho chlorine substituted PCB residues detected in a higher mammal in the wilderness. PMID- 3110079 TI - Gas and liquid chromatography of hydroxybiphenyls, chlorinated hydroxybiphenyls and several types of halogenated derivatives. I. Capillary gas chromatography and mass spectrometry. AB - For 8 hydroxybiphenyls and 19 chlorinated hydroxybiphenyls derivatization reactions with 6 electrophilic reagents--viz., 4 perfluoro anhydrides, pentafluorobenzoyl chloride and tert.-butylpentafluorophenylmethylchlorosilane- have been studied to evaluate their potential for capillary gas chromatography with electron-capture detection. For some of the classes of derivatives, mass spectrometric data are presented. PMID- 3110080 TI - Analytical methodology for organophosphorus pesticides used in Canada. AB - An overview of analytical methodology for the determination of organophosphate pesticides residues in foods is presented. Sample extraction is carried out with acetone followed by a dichloromethane-hexane partition. The organic extract is purified by automated gel permeation chromatography and analysed by capillary gas chromatography with flame photometric or thermionic detection. Confirmation can be carried out by a variety of chemical derivatization techniques including hydrolysis followed by reaction of the phosphate or phenol moiety, direct alkylation or trifluoracetylation. Thin-layer chromatography with enzyme inhibition detection can be used as a rapid screening technique or to confirm results obtained by gas chromatography. Liquid chromatography has not been used much for the determination of organophosphorus compounds in foods. PMID- 3110081 TI - Synthesis and conformational study of a cyclic hexapeptide analogue of somatostatin: cyclo(Phe-D-Trp-Lys-Thr-o-AMPA). AB - The active sequence Phe7-D-Trp8-Lys9-Thr10 of somatostatin has been cyclized through o-(aminomethyl)phenylacetic acid, a spacer molecule, designed to mimic a Gly-Gly dipeptide containing a cis-constrained peptide bond. The resulting analogue shows no GH-inhibition. A 2D n.m.r. study reveals conformations different from the proposed bio-active one and still sensitive to the medium (solvent). PMID- 3110082 TI - Synthesis and conformational study of two cyclic analogues of somatostatin containing an AMPA-spacer unit. AB - Two cyclic somatostatin analogues containing the active sequence Phe7-D-Trp8-Lys9 Thr10 and a meta- or para-(aminomethyl) phenylacetic acid (AMPA) spacer unit, have been synthesized. A conformational study using 2D n.m.r. techniques (COSY, NOESY) reveals that the conformation of the meta-AMPA analogue has some analogy with the bio-active conformation proposed earlier by Veber and colleagues, while in the para-AMPA analogue an equilibrium exists between a beta-II' turn and a gamma-turn structure. Both analogues show no GH-inhibition or LH-inhibition in in vitro assays. PMID- 3110083 TI - Reactivity of consecutive basic amino acid residues in peptides. AB - Different tetrapeptides of general formula L-Ala-X-X-Gly, possessing a basic doublet in the second and third position (X = Arg or Lys), have been synthesized as free or N-acetylated molecules. The chemical reactivity of the arginine guanidino group and of the lysine epsilon-amino group were studied using respectively the Sakaguchi and the ortho-diacetylbenzene reactions, in the tetrapeptides as well as in related molecules. In both cases, the colour yield is markedly influenced by the length of the polypeptide chain and by the relative positions of the arginine and lysine residues, suggesting the occurrence of intramolecular bonds within the tetrapeptide molecule. Tryptic hydrolysis of the tetrapeptides was followed by evaluating the amino acids or peptides which appear to be specific for the different possible cleavages at the arginyl or at the lysyl bonds. The susceptibility to trypsin of the carboxylic group of the second basic amino acid decreases progressively in the order Lys-Arg greater than Arg Arg much greater than Lys-Lys greater than Arg-Lys, which shows a fair correlation with the intra-cellular cleavage of the bonds observed during the processing of preproteins of of the precursors of several physiologically active peptides. PMID- 3110084 TI - The response of murine stem spermatogonia to radiation combined with 3 aminobenzamide. AB - The influence of 3-aminobenzamide (3-AB) on the radiation response of the stem spermatogonia of the CBA mouse has been investigated. Doses of 3-AB from 66 to 450 mg/kg, administered 1 h before irradiation, significantly enhanced stem-cell killing. Enhancement was observed when 3-AB (450 mg/kg) was given up to 5 h before, but not if administered after, irradiation. When radiation was delivered at a lower dose rate (5 cGy/min compared to 180 cGy/min) significant dose sparing was achieved for radiation alone. Pretreatment with 3-AB resulted in slightly less enhancement at the low dose rate than at the high. Split-dose studies (9 Gy total dose) with radiation alone resulted in a recovery ratio of 1.4-1.5. Administration of 3-AB before the first dose resulted in a similar recovery ratio, but if given immediately after the first dose the ratio was smaller. Pretreatment of mice with the radiosensitizer RSU-1069 indicated that at least some of the stem cells were radiobiologically hypoxic. We suggest therefore that the enhancement of spermatogonial stem-cell killing by 3-AB is not entirely due to inhibition of repair processes but may also involve modification of the oxygen status of the testis. PMID- 3110085 TI - Changes of vascular endothelial cell shape and of membrane potential in response to the ionophore A23187. AB - Endothelial cells lining the thoracic inferior vena cavae of guinea-pigs were depolarised by exposure in vitro to the ionophore A23187, as judged by intracellular glass microelectrodes. There was also a simultaneous rounding up of the cell, as demonstrated by electron microscopy. Both depolarisation and change of cell shape occurred in the absence of extracellular calcium ions. Prior exposure of the endothelium to verapamil prevented both the depolarisation and the change of cell shape induced by A23187. In contrast, pretreatment with indomethacin prevented the change of cell shape but not the depolarisation induced by A23187. Possible mechanisms of action of these substances on the endothelial cell are discussed. PMID- 3110086 TI - Effects of alpha-MSH, TRH and AVP on learning and memory, pain threshold, and motor activity: preliminary results. AB - The effect of daily peripheral administration of various peptides on learning and memory performance was studied in male albino rats. Groups of rats were treated with either TRH (1.0 mg/kg) alpha-MSH (1.0 mg/kg), or saline for three days. Other groups were treated either with vasopressin (1.0 microgram/kg) or saline. All treatments were 30 min before testing in a Morris Water Task apparatus. This type of learning is spatial learning which requires integration of environmental cues. Only alpha-MSH treated rats exhibited improved learning on Day 1 and Day 3 of the training period. One month later all rats were retested with no difference between the experimental groups. Single doses of these peptides caused a nonsignificant increase in pain threshold. The body weight gain of vasopressin treated rats was significantly reduced as well as their motoric behavior. Therefore, the alpha-MSH effect on learning cannot be explained by nonspecific effects on body weight, pain threshold, or motor activity level. PMID- 3110087 TI - Measurement of cognitive abilities in senescent animals. AB - The behavioral paradigms used in investigating for differences in the cognitive abilities of young and aged animals are critically reviewed with regard to their power to discriminate between young and aged animals' mental capacity. Irrespective of the kind of task, geronto-behavioral research especially is afflicted with difficulties in controlling motivational and emotional influences on cognitive processes. It is hypothesized-somewhat provocatively-that most of the findings indicating an age-related decline are better attributed to the altered motivational status and/or emotional reactiveness than to impaired cognitive processes of senescent animals. Of the common tasks used in this field, it is concluded that complex mazes and different delayed response tasks seem to represent appropriate paradigms in order to study changed capacities in short- and long-term memory (working- and reference-memory, respectively). PMID- 3110088 TI - Antiinflammatory drugs and the many mediators of inflammation. AB - The history of the use of aspirin and salicylate is briefly reviewed, as are the many putative mediators of inflammation. The theory that aspirin-like drugs bring about their antiinflammatory effects through inhibition of prostaglandin biosynthesis is presented, in the light of other arachidonic acid products such as the leukotrienes. Evidence is presented that aspirin brings about its antiinflammatory effects (at least in the rat) after its conversion into salicylate. The selective inhibition of cyclooxygenase by the large group of aspirin-like non-steroid antiinflammatory drugs explains their therapeutic activity. The elucidation of other pathways of oxidative metabolism of arachidonic acid has revealed new targets for the development of drugs with potentially greater therapeutic activity in the treatment of inflammation, cardio thrombotic diseases and asthma. PMID- 3110090 TI - [Pancreas and islands of Langerhans transplantation in diabetes mellitus]. PMID- 3110089 TI - Effect of hrTNF alpha on TxB2 release by macrophages. AB - Peritoneal rat macrophages incubated with human recombinant tumour necrosis factor (hrTNF alpha) released 2-3 times more thromboxane (TxB2) than untreated macrophage controls, a result similar to that obtained by incubating them with endotoxin (ET) or calcium ionophore A23187. PMID- 3110091 TI - Hexose monophosphate shunt in rat lens: stimulation by vitamin C. AB - The metabolism of glucose through the hexose monophosphate (HMP) shunt has been studied in rat lens in vitro, in the absence and presence of ascorbic and dehydroascorbic acids. Both forms of the vitamin stimulated the utilization of glucose through the HMP shunt, the stimulatory effect of dehydroascorbate being substantially greater than that of ascorbate. The stimulatory effect of ascorbate, as well as of dehydroascorbate, was antagonized by sodium iodide, and N,N-bis (dichloroethyl)-N-nitrosourea, compounds known to inhibit glutathione reductase. N-ethylmaleimide also antagonized the stimulation. These findings, therefore, suggest that the DHA/AA redox couple acts in concert with the GSSG/GSH couple in stimulating the tissue shunt activity. PMID- 3110092 TI - Immunopathology of acute experimental histoplasmic choroiditis in the primate. AB - The immunopathologic features of experimental acute histoplasmic choroiditis were studied in the nonhuman primate. Using an indirect immunoperoxidase technique, a panel of hybridoma-derived anti-human monoclonal antibodies, recognizing distinct lymphoid cell and macrophage surface antigens, have been adapted for use in the primate system. Twenty-two individual foci of histoplasmic choroiditis from five eyes were studied at time periods from 20 to 60 days post intracarotid injection of yeast phase Histoplasma capsulatum. A mononuclear and granulocytic cell infiltration was seen in all lesions. The predominant cell type was the CAPPEL+ T lymphocyte (suppressor/cytotoxic subset). Other cell types found in smaller numbers were OKT4+ T cells (helper/inducer subset), OK7+ (peripheral B lymphocytes), IgD+ (mantle B cells) and OKM1+ cells (macrophages and polymorphonuclear leukocytes). Herein, we present immunopathologic data on the acute phase of experimental ocular histoplasmosis. PMID- 3110093 TI - Synthesis of slow-reacting substance-like activity in human anterior uvea. AB - The present study demonstrates that human anterior uvea synthesizes a 5 lipoxygenase product termed slow-reacting substance (SRS) (a mixture of leukotrienes, C4, D4 and E4) from arachidonic acid (AA). Characterization of SRS was done using the guinea pig ileum (GI) as bioassay tissue. SRS contracted GI and this contraction was antagonized by FPL55712, a leukotriene antagonist. The synthesis of SRS was enzymatic in nature since boiled or BW 755-treated tissues did not synthesize SRS-like activity from AA. Further confirmation that the substance was SRS-like came from the measurement of LTC4-like immunoreactivity. PMID- 3110095 TI - Should doctors worry about health care costs? PMID- 3110096 TI - A genetic and molecular analysis of the alpha glycerophosphate cycle in Drosophila melanogaster. PMID- 3110094 TI - Effect of interferon alpha, interferon beta, and interferon gamma on the in vitro growth of human renal adenocarcinoma cells. AB - Interferon-alpha, interferon-beta, and interferon-gamma differ in their antiproliferative effects for several cell lines. Interferons were thus assessed for their activity in inhibiting proliferation of three renal cell carcinoma cell lines. The malignant epithelial phenotype of each of these cell lines was confirmed by electron microscopy, histology, karyotype and tumorigenicity. When compared on an anti-viral unit basis, naturally produced interferon-beta was more effective than natural interferon-alpha for all cell lines and clones. Proliferation of each of the cell lines was inhibited by interferon-gamma. In all cases, removal of interferons from culture media resulted in resumption of the rate of cell growth after a variable delay of 6-10 days. If the antiproliferative effects of interferons predominate in mediating tumor regression, clinical response may depend upon the type of interferon to which the tumor is exposed. PMID- 3110097 TI - Structural organization of the alpha-amylase gene locus in Drosophila melanogaster and Drosophila miranda. AB - Chromosomal sites belonging to the alpha-amylase gene family have been identified in D. melanogaster and D. miranda and in the sibling species of miranda, pseudoobscura, and persimilis. Two sites occur in chromosome 2 of melanogaster; one contains the Amy gene locus (54A) and the other an amylase "pseudogene" (53CD). Two sites of homology exist at 73A and 78C and perhaps another at 81BC in chromosome 3 of pseudoobscura and persimilis and in the homologous regions of the X2 chromosome in miranda. The active Amy locus is apparently at 73A. The structural organization of cloned sequences from this multigene family in melanogaster and miranda is under analysis, with emphasis on the functional Amy gene region. Electrophoretic variants of amylase have served as invaluable tools in these studies. For melanogaster, their use as genetic markers enabled us to positively identify our lambda Dm65 clone of the Amy locus and to show that it contains two functional copies of the structural gene for alpha-amylase. Amylase isozymes are now being used in P element-mediated transformation experiments aimed at defining regulatory elements for the temporal and spatial control of amylase expression during development and in response to dietary glucose. In miranda, electrophoretic variants of amylase were useful in assigning the Amy locus to chromosome X2, and they continue to serve as essential markers in our study of the evolution of dosage compensation for amylase expression in males of this species. Restriction maps of the Amy locus in 7 strains of D. melanogaster indicate that despite the worldwide origins of the chromosome samples, all contain a duplication of the amylase structural gene at this locus regardless of whether they produce two alpha-amylase isozymes, a single variant, or none. We have aligned these maps with the genetic and cytological maps of chromosome 2R in melanogaster and assigned alleles for different amylase isozymes to either the proximal or distal Amy gene copy in a number of strains. Restriction site polymorphism is relatively limited at the Amy locus, but some strain-specific rearrangements exist. The locus of two strains with reduced amylase activity, Amy1 (CA 1) and Amy "null", contain anomalies--an insertion in the former and an inversion in the latter. Causal relationships are being sought between the level of amylase expression in these strains and the position of their respective anomalies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3110098 TI - Molecular genetics of carbonic anhydrase isozymes. PMID- 3110099 TI - Terminal trajectory: compassion, comfort, and dignity. PMID- 3110100 TI - Pentylenetetrazol-induced spike wave discharges in rats: a polygraphic study. AB - 14 male Wistar rats were studied, before and after pentylenetetrazol (PTZ) 20 mg/kg i.p., since a petit mal-like electroclinical pattern, either spontaneous or PTZ-induced was recently described in a breeding station where this strain is raised. In particular, surface EEG, muscular, respiratory and cardiac activities were recorded in order to detect possible clinical-electroencephalographic correlations. Spontaneous epileptic phenomena were never observed. In all the animals PTZ-induced short, usually generalized and synchronous spike wave discharges often concomitant with rhythmic twitches of the vibrissae. Epileptic bursts were related to arousal level, disappearing during motor behavior and arousing stimuli. Moreover individual discharges could be interrupted by a sudden noise. Photosensitivity was not present. Muscular tone and autonomic functions were not affected. The features of PTZ-induced generalized nonconvulsive seizures in rats are compared to those of cat penicillin epilepsy and human petit mal. PMID- 3110102 TI - Chronic cluster headache--a review of 60 patients. PMID- 3110101 TI - The effect of alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on mitogen-induced interleukin 2 production. AB - The objective of the present investigation was to examine the effect of DL-alpha difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, on mitogen-induced interleukin 2 production. Treatment with DFMO reduced nylon wool T cell polyamine levels. In contrast, DFMO treatment enhanced, greater than two-fold, detectable levels of concanavalin A-induced interleukin 2 activity. This observed augmentation was not limited to in vitro DFMO treatment, since oral administration of DFMO to C57BL/6 mice also enhanced concanavalin A induced interleukin 2 levels in vitro. Treatment with exogenous putrescine reversed the effect of DFMO on interleukin 2 levels. These results suggest that the effect of DFMO on interleukin 2 levels is mediated through polyamines. Therefore, polyamine biosynthesis may play a role in the intracellular regulation of interleukin 2 production. PMID- 3110103 TI - Unmasking latent dysnociception in healthy subjects. PMID- 3110104 TI - Cognitive therapy and relaxation training in muscle contraction headache: efficacy and cost-effectiveness. PMID- 3110105 TI - Effectiveness and cost effectiveness of persuasive communications and incentives in increasing safety belt use. AB - The Safety Belt Connection Project was a worksite health promotion project conducted at a medical school and hospital complex to test the effectiveness and cost effectiveness of four treatment conditions (TCs): TC1, Persuasive Communications (PCs) alone; TC2, PCs plus overt monitoring; TC3, PCs plus incentives; and TC4, PCs plus incentives and prompts. Parking lots were randomized to treatment condition. A community traffic intersection served as a comparison group. Trained observers recorded safety belt use rates (SBURs) of subjects (front seat occupants) over a two-week period at baseline and after a four-week period of intervention. Results were analyzed by chi-square comparisons of pre-treatment and post-treatment SBURs. At baseline, significant differences in SBURs between treatment groups were observed. Significant pre-to-post differences were found for TC3 and TC4: the SBUR in TC3 went from 18.3% - 38.4% (p less than 0.001) and the SBUR in TC4 went from 16.9% - 44.8% (p less than 0.001). Both TC3 and TC4 were effective, but TC4 cost 2.6 times more per person influenced to wear their safety belt. PMID- 3110106 TI - Determination of time required for blood gas homeostasis in the intubated post open-heart surgery adult after a ventilator change. PMID- 3110108 TI - Tissue-type plasminogen activator. PMID- 3110107 TI - Phenomena of respiration: historical overview to the twentieth century. PMID- 3110109 TI - The effect of lipophilic substituents on the biological properties of EDTA complexes containing paramagnetic metal ions. AB - Complexes of the radioactive paramagnetic metal ions 51Cr(III), 54Mn(II), 59Fe(III), 57Co(II), 64Cu(II) and 153Gd(III) were prepared with EDTA and its derivative containing the lipophilic 1-(4-methylphenyl)-group (MPEDTA), together with the corresponding 99mTc-compounds. The formation of these complexes was verified by electrophoresis and they were screened for potential use as MRI hepatobiliary contrast agents by biodistribution studies in mice. In this series, the MPEDTA complexes of 54Mn(II) and 64Cu(II) showed increased urinary excretion compared to the unsubstituted EDTA complexes, while the MPEDTA complexes of 99mTc, 59Fe, 57Co, 153Gd and particularly 51Cr demonstrated improved hepatobiliary excretion. Further lipophilic substitution should enhance this property but the preparation of such ligands is complicated by cyclisation reactions. PMID- 3110110 TI - [Cost-benefit analysis of ambulatory surgery]. PMID- 3110111 TI - Relation between tolerance to ethanol and alcohol dehydrogenase (ADH) activity in Drosophila melanogaster: selection, genotype and sex effects. AB - The suggestion of Oakeshott et al. (1984) that selection at the Adh locus, as a response to ethanol, is restricted to D. melanogaster laboratory-adapted populations, is tested in this paper with the "Lagar de los Reyes" (LR) lines. For this purpose, homozygous lines for the AdhF and the AdhS alleles were maintained on food supplemented with ethanol. After the selection, the ethanol tolerance and the ADH activity of the selected flies (LRSeF and LRSeS) were determined and compared with those of the control flies (LRCF and LRCS), maintained on standard medium. Then, the effects of the selection, genotype and sex, and the relation between ethanol tolerance and ADH activity were analysed. Our results fail to show a consistent correlation between ethanol tolerance and ADH activity in the adults of LR lines. Our findings also indicate that adaptation of D. melanogaster to ethanol-containing food could be accomplished without significant changes on the ADH activity in the adults. The possibility that the adaptation of D. melanogaster to environmental ethanol could be independent of the Adh locus is discussed. PMID- 3110112 TI - Biosynthesis of chlortetracycline. Part III--Hydroxylation of L-phenylalanine to L-tyrosine by Streptomyces aureofaciens and its relation to the biosynthesis of chlortetracycline. PMID- 3110113 TI - Effect of chloramphenicol on nitrogen fixation in a cyanobacterium. PMID- 3110114 TI - Newer approaches for improving Streptomyces strains. I. Studies on protoplast fusion of S. griseus. PMID- 3110115 TI - The binding of epidermolytic toxin from Staphylococcus aureus to mouse epidermal tissue. AB - Fluorescein-labelled epidermolytic toxin (FTC-toxin) of Staphylococcus aureus and ferritin-toxin conjugate have been prepared and purified. FTC-toxin bound selectively to cryostat and resin-impregnated sections of neonatal mouse skin. Binding was localized at the keratohyalin granules and in the stratum corneum. In an epidermal cell (granular, spinous and basal) preparation, only keratohyalin granules of the granular cells bound FTC-toxin. Ferritin-toxin conjugate bound to skin sections at the same two sites as FTC-toxin and was competitive with the binding of free toxin. Keratohyalin granules in unstained sections had a novel 'patched' appearance under the electron microscope, and the ferritin-toxin conjugate bound preferentially to the electron-lucent areas. In the stratum corneum it was shown by quantitative estimation that the target density decreased as the surface of the tissue was approached. PMID- 3110117 TI - A numerical taxonomic study of psychrotrophic bacteria associated with lipolytic spoilage of raw milk. AB - Raw milk samples were stored for 1-4 d and examined for bacterial growth and lipase activity. Thirty-six samples in which an increase in the heat-stable lipase activity was observed during storage were selected for further study. From these raw milk samples 205 lipolytic psychrotrophic strains were selected using butterfat agar and subsequently characterized with 86 taxonomic tests. Complete linkage cluster analysis of the taxonomic data produced two major and six minor clusters at the 83% similarity level. Pseudomonas fluorescens and Ps. fragi accounted for 63.9 and 31.2%, respectively, of the isolates. PMID- 3110116 TI - Amino acid excesses for young pigs: effects of excess methionine, tryptophan, threonine or leucine. AB - Five experiments involving 359 weanling (8 kg) pigs were conducted to evaluate the effects of dietary excesses of DL-methionine (Met), L-tryptophan (Trp), L threonine (Thr) or L-leucine (Leu) when added to a 20% crude protein corn-soybean meal (C-SBM) diet. Experiments involved supplementing the basal diet with 0, .5, 1.0, 2.0 or 4.0% excesses of Met, Trp or Thr, or in the case of Leu, a 0, 1.0, 2.0, 4.0 or 6.0% excess. Levels of .5 and 1.0% excess Met did not depress feed intake (FI), weight gain (G) or gain/feed (G/F); 2.0 and 4.0% additions, however, depressed both FI and G but not G/F. Free Met in blood plasma increased linearly as dietary Met level increased, reaching over a 100-fold elevation at the highest Met level fed. Plasma Thr and serine (Ser) increased, and glycine (Gly) decreased, with each added increment of Met. With Trp, only the 4.0% addition depressed FI and G (but not G/F). None of the levels of excess Thr depressed performance. Excess Thr, in fact, tended to increase G/F. Free Thr, Ser and Gly in plasma increased linearly as graded increments of excess Thr were added to the diet. With Leu, a 6% addition depressed weight gain and food intake (but not G/F) but 1, 2 or 4% excesses were without effect. Plasma free Leu increased linearly while free isoleucine and valine decreased as graded increments of Leu were added to the diet. These results suggest that pigs can tolerate considerable excesses of Met, Trp, Thr and Leu without experiencing decreased voluntary feed intake or weight gain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110118 TI - Factors affecting the germination of spores of Bacillus anthracis. AB - Spores of Bacillus anthracis germinated poorly at high cell densities unless the alanine racemase inhibitor O-carbamyl-D-serine was added to the germination medium. Spores derived from a variety of strains of B. anthracis germinated optimally at 22 degrees C. No correlation was found between rate of spore germination and virulence or between susceptibility of animal species to anthrax and spore germination rate using sera from those animals as the germination medium. PMID- 3110119 TI - Effect of cardiogenic gas mixing on arterial O2 and CO2 tensions during breath holding. AB - To examine the effect of cardiogenic gas mixing on gas exchange we measured arterial tension of O2 (PaO2) and arterial tension of CO2 (PaCO2) during 3- to 5 min breath holds (BH) before and after infusing 50 ml of saline into the pericardial space (PCF) of seven anesthetized, paralyzed, mechanically ventilated dogs. During BH the ventilator was disconnected and a bias flow of 50% O2 at 4-5 l/min was delivered through the side ports of a small catheter whose tip was positioned 1 cm cephalad of the carina. Paired runs, alternately with and without PCF, were performed in triplicate in each dog. Initial PaO2 was similar for control runs [81 +/- 3 mmHg (SE)] and PCF runs (78 +/- 3 mmHg; P greater than 0.1). After 3-min BH, PaO2 in PCF runs (33 +/- 3 mmHg) was less than that in control runs (58 +/- 4 mmHg) (P less than 0.001). In contrast, the pattern of PaCO2 during BH did not differ with PCF. After 3-min BH, PaCO2 was 49 +/- 3 mmHg with PCF and 49 +/- 2 mmHg in the control runs (P greater than 0.7). In two dogs, repeated 50-ml reductions in lung volume, produced by rib cage compression, did not alter the time course of PaO2 during BH. Although cardiac output decreased slightly with PCF, hemodynamic changes due to PCF were unlikely to account for the observed fall in PaO2. Our results indicate a substantial effect of cardiogenic gas mixing on O2 uptake when tracheal gas is O2 enriched during breath holding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110120 TI - Effect of high-intensity exercise on the VE-VCO2 relationship. AB - The intrinsic relationship between ventilation (VE) and carbon dioxide output (VCO2) is described by the modified alveolar ventilation equation VE = VCO2 k/PaCO2(1-VD/VT) where PaCO2 is the partial pressure of CO2 in the arterial blood and VD/VT is the dead space fraction of the tidal volume. Previous investigators have reported that high-intensity exercise uncouples VE from VCO2; however, they did not measure the PaCO2 and VD/VT components of the overall relationship. In an attempt to provide a more complete analysis of the effects of high-intensity exercise on the VE-VCO2 relationship, we undertook an investigation where five subjects volunteered to perform three steady-state tests (SS1, SS2, SS3) at 60 W. One week after SS1 each subject was required to perform repeated 1-min bouts of exercise corresponding to a work rate of approximately 140% of maximal oxygen uptake (VO2max). Two and 24 h later the subjects performed SS2 and SS3, respectively. This exercise intervention caused PaCO2 during SS2 and SS3 to be regulated (P less than 0.01) approximately 4 Torr below the control (SS1) value of 38.8 Torr. Additionally, significant alterations were noted for VCO2 with corresponding values of 1.15 (SS1), 1.10 (SS2), and 1.04 (SS3) l/min. No changes were noted in either VD/VT or VE. In summary, it seems reasonable to suggest that the disproportionate increase in VE with respect to VCO2 noted in earlier work does not reflect an uncoupling. Rather the slope of the VE-VCO2 relationship is increased in a predictable manner as described by the modified alveolar ventilation equation. PMID- 3110121 TI - Changes in lung volume and breathing pattern during exercise and CO2 inhalation in humans. AB - Lung volume changes during CO2 inhalation and exercise were compared in seven human subjects. Expiratory reserve volume (ERV) normalized by vital capacity (VC) was used as an index of end-expiratory lung volume (EELV). Work loads tried were 30, 60, and 90 W and inspired CO2 concentrations were 3.5 and 5.0%. Exercise at 30 W led to a significant decrease in EELV, by 7% VC (P less than 0.005), with no further change at higher levels of exercise (P greater than 0.1). Both 3.5 and 5.0% CO2 inhalation resulted in an increase in EELV that was not statistically significant (3% VC, P greater than 0.1). A possible linkage of this different EELV behavior to breathing pattern was tested. The tidal volume-inspiratory duration curve shifted to a higher volume region during exercise compared with CO2 inhalation. Consequently, the volume-time threshold characteristic was better described by an end-inspiratory lung volume-inspiratory duration plot, resulting in a common relationship under these two different stimuli. These results suggest that the depth and rate of breathing in humans can be affected by not only phasic but also tonic components. A decrease in functional residual capacity or EELV was peculiar to exercise and should be associated with increased mechanical efficiency compared with CO2 inhalation. Theoretical predictions based on work of breathing optimization via a decreased EELV seemed to be capable of explaining isocapnic exercise hyperpnea in conjunction with proportional control of arterial CO2 tension. PMID- 3110122 TI - Evidence that hypoxic pulmonary vascular remodeling in rats is polyamine dependent. AB - This study tested the hypothesis that the polyamines, a family of low-molecular weight organic cations with documented regulatory roles in cell growth and differentiation, are mediators of chronic hypoxia-induced pulmonary vascular remodeling. Relative to room air controls, chronically hypoxic animals (inspired O2 fraction = 0.1; 21 days) exhibited higher pulmonary arterial pressures (measured in room air), thicker medial layers in pulmonary arteries of 50-100 microns diam, increased hematocrits, and right ventricular hypertrophy. In addition, lung contents of the polyamines, putrescine, spermidine, and spermine were greater in hypoxic animals than in controls. alpha-Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, attenuated the hypoxia-induced elevations in lung putrescine and spermidine content and blunted the increases in pulmonary arterial pressure and medial thickness. Neither the increased hematocrit nor right ventricular hypertrophy associated with chronic hypoxia were abrogated by DFMO. In addition, DFMO failed to influence vasoconstrictor responses provoked by acute hypoxic ventilation in isolated, buffer-perfused rat lungs. These observations suggest that depression of polyamine biosynthesis with DFMO blunts the sustained increase in pulmonary arterial pressure by attenuating hypoxia-induced medial thickening. PMID- 3110123 TI - Dry air-induced constriction: effects of pharmacological intervention and temperature. AB - We studied airway wall temperature (Taw) during dry air challenge of the canine lung periphery. We measured collateral resistance (Rcs) before and after periods of elevated airflow using a wedged bronchoscope technique. As flow rate increased, Taw dropped and postchallenge Rcs rose. A significant negative correlation was found between Taw recorded during challenge and Rcs observed 5 min after challenge. Repetitive dry air challenge produced similar changes in Rcs and Taw. However, responses to warm moist air were significantly lower than consecutive responses to dry air. Taw was significantly lower during dry air challenge than during moist air challenge. Indomethacin (5 mg/kg) and atropine (1 mg/kg) reduced responses to dry airflow challenge. Indomethacin did not affect Taw during the challenge, whereas atropine reduced the fall in Taw. We conclude that temperature correlates negatively with peripheral lung tone 5 min after dry air challenge. This correlation holds under conditions where airflow is increased, air is humidified, or atropine is administered. The dissociation between Taw and physiological response after indomethacin likely reflects a decrease in mediators released during challenge. PMID- 3110124 TI - Carotid body chemosensory function in prolonged normobaric hyperoxia in the cat. AB - The effects of normobaric hyperoxia on carotid body chemosensory function in the cat were studied. The hypothesis was that carotid body chemosensory function would be affected by chronic exposure to 100% O2 at sea level. It was based on the assumptions that carotid body tissue is exposed to high PO2 because of its high blood flow and that its O2 chemosensing mechanism is sensitive to O2 radical induced reactions. Twelve cats were exposed to 100% O2 for 60-67 h, and 10 control cats were maintained in room air at sea level. They were anesthetized with pentobarbital sodium (Nembutal), and chemosensory afferents from a cut carotid sinus nerve were isolated and identified. The responses of single or a few clearly identifiable chemoreceptor afferents to isocapnic hypoxia and hypercapnia during hyperoxia and to the bolus injections of cyanide, nicotine, and dopamine were studied. We found that chronic hyperoxia severely blunted or eliminated the O2-sensitive response of the carotid chemoreceptors while augmenting the hypercapnic response. The response to cyanide but not to nicotine and dopamine were attenuated. Thus the hypoxic and hypercapnic responses that normally interact were separable. The lack of the cyanide response was consistent with the lack of the hypoxic response, suggesting a possible shared mechanism of carotid chemoreceptor response. Qualitatively normal responses to dopamine and nicotine indicated that the respective receptors were relatively intact after chronic exposure to hyperoxia and that the sensory nerves themselves were not affected by the prolonged O2 exposure. PMID- 3110125 TI - Effect of lung volume on breath holding. AB - The mechanism by which large lung volume lessens the discomfort of breath holding and prolongs breath-hold time was studied by analyzing the pressure waves made by diaphragm contractions during breath holds at various lung volumes. Subjects rebreathed a mixture of 8% CO2-92% O2 and commenced breath holding after reaching an alveolar plateau. At all volumes, regular rhythmic contractions of inspiratory muscles, followed by means of gastric and pleural pressures, increased in amplitude and frequency until the breakpoint. Expiratory muscle activity was more prominent in some subjects than others, and increased through each breath hold. Increasing lung volume caused a delay in onset and a decrease in frequency of contractions with no consistent change in duty cycle and a decline in magnitude of esophageal pressure swings that could be accounted for by force-length and geometric properties. The effect of lung volume on the timing of contractions most resembled that of a chest wall reflex and is consistent with the hypothesis that the contractions are a major source of dyspnea in breath holding. PMID- 3110127 TI - Measurement of O2 consumption, CO2 production, and water vapor production in a closed system. AB - Equations for the calculation of O2 consumption, CO2 production, and water vapor production in a constant-volume, closed-system respirometer are presented. Necessary measurements include only the initial temperature, pressure, and gas volume in the respirometer chamber, and the fractional concentration of O2 in gas samples taken at the beginning and end of the period of measurement. Potential errors resulting from changes in CO2 and water vapor concentrations are identified. Ignoring CO2 effects can produce up to a 6.4% error in estimates of O2 consumption, and errors due to water vapor effects can exceed 100%. Techniques are presented for minimizing potential errors and for measuring CO2 and water vapor concentrations with an O2 analyzer so that potential errors can be eliminated. PMID- 3110126 TI - Effect of interbreath fluctuations on characterizing exercise gas exchange kinetics. AB - Breathing has inherent irregularities that produce breath-to-breath fluctuations ("noise") in pulmonary gas exchange. These impair the precision of characterizing nonsteady-state gas exchange kinetics during exercise. We quantified the effects of this noise on the confidence of estimating kinetic parameters of the underlying physiological responses and hence of model discrimination. Five subjects each performed eight transitions from 0 to 100 W on a cycle ergometer. Ventilation, CO2 output, and O2 uptake were computed breath by breath. The eight responses were interpolated uniformly, time aligned, and averaged for each subject; and the kinetic parameters of a first-order model (i.e., the time constant and time delay) were then estimated using three methods: linear least squares, nonlinear least squares, and maximum likelihood. The breath-by-breath noise approximated an uncorrelated Gaussian stochastic process, with a standard deviation that was largely independent of metabolic rate. An expression has therefore been derived for the number of square-wave repetitions required for a specified parameter confidence using methods b and c; method a being less appropriate for parameter estimation of noisy gas exchange kinetics. PMID- 3110128 TI - A non-filamentous configuration of intermediate-sized filament proteins in Drosophila Kc tissue culture cells. AB - Using monoclonal antibodies against the major intermediate filament (10 nm) cytoskeletal proteins of Drosophila tissue culture cells, we showed by indirect immunofluorescence and immuno-electron microscopy that this cytoskeletal material also occurs in a non-filamentous configuration. Patches of fine granular material are detected in the cytoplasm of Kc cells but are absent in another Drosophila cell line (Schneider, line 2). These patches are surrounded by membranes with bound ribosomes, resembling endoplasmic reticulum, and are found throughout the cytoplasm. We suggest that these aggregates are caused by overproduction of intermediate filament material in the Kc cell line. PMID- 3110129 TI - Secretion of human serum albumin from Bacillus subtilis. AB - We have fused the structural gene (hsa) for human serum albumin (HSA) to the expression elements and signal sequence coding region of each of two genes from Bacillus amyloliquefaciens P, an alpha-amylase gene (amyBamP) and a neutral protease gene (nprBamP). Bacillus subtilis strains harboring either of these gene fusions synthesized a protein with the antigenic characteristics and size (68 kilodaltons) of HSA. Results from pulse-labeling studies indicated that the bacterially produced HSA was secreted from cells which had been converted to protoplasts. Results from similar studies with intact cells suggested that the signal sequence was removed from the hybrid protein, providing further evidence that B. subtilis can translocate this foreign protein across the cell membrane. Signal sequence removal was efficient when the level of HSA synthesis was low. However, in strains which synthesized HSA at a high level, signal sequence removal was less efficient. PMID- 3110131 TI - Genetic and physiological characterization of Bacillus subtilis mutants resistant to purine analogs. AB - Bacillus subtilis mutants defective in purine metabolism have been isolated by selecting for resistance to purine analogs. Mutants resistant to 2-fluoroadenine were found to be defective in adenine phosphoribosyltransferase (apt) activity and slightly impaired in adenine uptake. By making use of apt mutants and mutants defective in adenosine phosphorylase activity, it was shown that adenine deamination is an essential step in the conversion of both adenine and adenosine to guanine nucleotides. Mutants resistant to 8-azaguanine, pbuG mutants, appeared to be defective in hypoxanthine and guanine transport and normal in hypoxanthine guanine phosphoribosyltransferase activity. Purine auxotrophic pbuG mutants grew in a concentration-dependent way on hypoxanthine, while normal growth was observed on inosine as the purine source. Inosine was taken up by a different transport system and utilized after conversion to hypoxanthine. Two mutants resistant to 8-azaxanthine were isolated: one was defective in xanthine phosphoribosyltransferase (xpt) activity and xanthine transport, and another had reduced GMP synthetase activity. The results obtained with the various mutants provide evidence for the existence of specific purine base transport systems. The genetic lesions causing the mutant phenotypes, apt, pbuG, and xpt, have been located on the B. subtilis linkage map at 243, 55, and 198 degrees, respectively. PMID- 3110132 TI - prtR enhances the mRNA level of the Bacillus subtilis extracellular proteases. AB - Studies were performed on the prtR gene which enhances the production of the Bacillus subtilis extracellular proteases and levansucrase, but not the alpha amylase, RNase, and alkaline phosphatase. To investigate the mode of action of prtR, the Escherichia coli bla gene was placed under the control of two promoters. One was the promoter of the alkaline protease gene (aprE), and the other was the promoter of B. subtilis dihydrofolate reductase gene (dfrA). Expression of the bla gene was enhanced by prtR only when the apr promoter was used. From these results, it was concluded that the apr promoter or its vicinity was the target of prtR and that prtR does not affect the process after transcription. The mRNA levels of aprE and nprE (the neutral protease gene) were significantly increased by prtR, but the half-life of the aprE mRNA was not affected. These results show that the prtR gene product enhances protease production by increasing the rate of transcription initiation. PMID- 3110133 TI - Purification of aconitase from Bacillus subtilis and correlation of its N terminal amino acid sequence with the sequence of the citB gene. AB - The DNA sequence for the promoter region of the Bacillus subtilis citB gene has been determined. Presumed "-10" and "-35" regions of the promoter have been identified, and transcriptional and translational start points of citB have been located. To correlate the DNA sequence of citB with the amino acid sequence of its presumed product, aconitase, it was necessary to devise a scheme for purification of this labile enzyme. This procedure relies on the ability to restore enzyme activity at each stage of purification by incubation in a reducing buffer containing a source of ferrous ions. B. subtilis aconitase appears to be a monomer with a molecular weight of approximately 120,000. The amino-terminal amino acids of aconitase fit the sequence predicted by analysis of the citB gene. Thus, citB codes for aconitase. PMID- 3110130 TI - Hybrid Escherichia coli sensory transducers with altered stimulus detection and signaling properties. AB - The tar and tap loci of Escherichia coli encode methyl-accepting inner membrane proteins that mediate chemotactic responses to aspartate and maltose or to dipeptides. These genes lie adjacent to each other in the same orientation on the chromosome and have extensive sequence homology throughout the C-terminal portions of their coding regions. Many spontaneous deletions in the tar-tap region appear to be generated by recombination between these regions of homology, leading to gene fusions that produce hybrid transducer molecules in which the N terminus of Tar is joined to the C terminus of Tap. The properties of two such hybrids are described in this report. Although Tar and Tap molecules have homologous domain structures, these Tar-Tap hybrids exhibited defects in stimulus detection and flagellar signaling. Both hybrid transducers retained Tar receptor specificity, but had reduced detection sensitivity. This defect was correlated with the presence of the C-terminal methyl-accepting segment of Tap, which may have more methylation sites than its Tar counterpart, leading to elevated steady state methylation levels in the hybrid molecules. One of the hybrids, which carried a more extensive segment from Tap, appeared to generate constitutive signals that locked the flagellar motors in a counterclockwise rotational mode. Changes in the methylation state of this transducer were ineffective in cancelling this aberrant signal. These findings implicate the conserved C terminal domain of bacterial transducers in the generation or regulation of flagellar signals. PMID- 3110135 TI - Expression of competence genes in Bacillus subtilis. AB - A set of competence (com) mutants of Bacillus subtilis was constructed by using Tn917lacZ as a mutagen. In about half of the mutants, the promoterless lacZ element on the transposon was placed under control of putative com promoters. Expression of the mutant com genes was studied by using the beta-galactosidase tag. Two of the mutant genes (those represented by com-124 and com-138) were expressed early in the growth cycle in all of the media tested and were not dependent on the spo0A or spo0H product for expression. The remaining mutants, which represented a minimum of four additional genes, expressed beta galactosidase in stationary phase during the period in which competence developed. We conclude that expression of com genes is probably regulated transcriptionally and in a growth stage-specific manner. Expression of these genes was also dependent on growth in competence medium and, like competence development, required the presence of glucose and was dependent on the spo0H products. The dependence on the spo0A gene product was partially bypassed by the abrB703 mutation. These effects were qualitatively equivalent to those on competence development. The latter was dependent on spo0A and spo0H, and the spo0A dependency was partially suppressed by abrB703. Several of the mutants were still capable of resolution into light and heavy buoyant density cell fractions when grown in competence medium. All of these expressed beta-galactosidase to a greater extent in the light fraction, showing that expression of these com genes was cell type specific. Development of competence was not markedly affected by mutations in spo0B, spo0E, spo0F, spo0J, or sigB, the structural gene of sigma 37. PMID- 3110134 TI - Relationship between aconitase gene expression and sporulation in Bacillus subtilis. AB - The citB of Bacillus subtilis codes for aconitase (D. W. Dingman and A. L. Sonenshein, J. Bacteriol. 169:3060-3065). By direct measurements of citB mRNA levels and by measurements of beta-galactosidase activity in a strain carrying a citB-lacZ fusion, we have examined the expression of citB during growth and sporulation. When cells were grown in nutrient broth sporulation medium, citB mRNA appeared in mid- to late-exponential phase and disappeared by the second hour of sporulation. This timing corresponded closely to the kinetics of appearance of aconitase enzyme activity. Decoyinine, a compound that induces sporulation in a defined medium, caused a rapid simultaneous increase in aconitase activity and citB transcription. After decoyinine addition, the rate of increase in aconitase activity in a 2-ketoglutarate dehydrogenase (citK) mutant and in a citrate synthase (citA) mutant was significantly less than in an isogenic wild-type strain. This is apparently due to a failure to deplete 2 ketoglutarate and accumulate citrate. These metabolites might act as negative and positive effectors of citB expression, respectively. Mutations known to block sporulation at an early stage (spo0H and spo0B) had no appreciable effect on citB expression or aconitase activity. These results suggest that appearance of aconitase is stimulated by conditions that induce sporulation but is independent of certain gene products thought to act at an early stage of sporulation. PMID- 3110136 TI - Construction and use of signal sequence selection vectors in Escherichia coli and Bacillus subtilis. AB - To study the diversity and efficiency of signal peptides for secreted proteins in gram-positive bacteria, two plasmid vectors were constructed which were used to probe for export signal-coding regions in Bacillus subtilis. The vectors contained genes coding for extracellular proteins (the alpha-amylase gene from Bacillus licheniformis and the beta-lactamase gene from Escherichia coli) which lacked a functional signal sequence. By shotgun cloning of restriction fragments from B. subtilis chromosomal DNA, a great variety of different export-coding regions were selected. These regions were functional both in B. subtilis and in E. coli. In a number of cases where protein export had been restored, intracellular precursor proteins of increased size could be detected, which upon translocation across the cellular membrane were processed to mature products. The high frequency with which export signal-coding regions were obtained suggests that, in addition to natural signal sequences, many randomly cloned sequences can function as export signal. PMID- 3110137 TI - Pseudosecretion of Escherichia coli chloramphenicol acetyltransferase by Bacillus subtilis. AB - Bacillus subtilis harboring the vector 25RBSII secrets an Escherichia coli derived chloramphenicol acetyltransferase into culture supernatants. The secreted enzyme lacks 18 amino acids; these are removed externally rather than during secretion. PMID- 3110139 TI - Prediction of therapeutic lithium dose: comparison and improvement of current methods. AB - The predictive value of two methods of predicting therapeutic lithium dose was evaluated in 19 patients. A single time point lithium level determination method, modified by the use of a 900-mg instead of a 600-mg test dose, was found to be a reliable and safe predictor. A mathematical model used for predictions was found to be moderately accurate but to generally predict a lower dose than was actually required. PMID- 3110140 TI - Affinity purification and characterization of serine hydroxymethyltransferases from rat liver. AB - A rapid and simple method was developed for the purification of serine hydroxymethyltransferases [EC 2.1.2.1]. The procedure involved ammonium sulfate precipitation, DEAE-cellulose column chromatography and affinity chromatography on an L-adsorbent. Through this procedure the cytosolic enzyme (s-SHMT) was purified 1,650-fold, and the mitochondrial enzyme (m-SHMT) 1,730-fold, with a yield of more than 30% in both cases. Both preparations gave a single band with a Mr of 54,000 on SDS-PAGE. The native enzymes both contained 4 mol of pyridoxal phosphate/mol of enzyme, and showed a Mr value of 220,000 on gel filtration, indicating a tetrameric structure. Several other properties of the enzymes were also studied. PMID- 3110138 TI - Chromosomal locations of three Bacillus subtilis din genes. AB - Previously isolated DNA damage-inducible (din) genes of Bacillus subtilis have been mapped on the bacterial chromosome by bacteriophage PBS1-mediated transduction. The din genes have been localized to three positions on the B. subtilis map. dinA cotransduction with the hisA locus was 80%, while dinC cotransduction with this marker was about 56%. dinB is unlinked to hisA, but its cotransduction with the dal-1 and purB loci was 84 and 22%, respectively. PMID- 3110141 TI - Physicochemical characterization of lens crystallins from the carp and biochemical comparison with other vertebrate and invertebrate crystallins. AB - Lens crystallins were isolated from the homogenate of carp (Cyprinus carpio) eye lenses by gel permeation chromatography and characterized by gel electrophoresis, immunodiffusion, amino acid analysis, circular dichroism, and protein sequence analysis. Three well-defined fractions corresponding to alpha/beta-, beta-, and gamma-crystallins were obtained in relative weight percentages of 26, 22, and 52%. The native molecular masses of the purified fractions were determined to be 410, 60, and 20 kDa, respectively. The polypeptide compositions as determined by SDS gel electrophoresis revealed the substantial presence of beta-crystallin polypeptides in the alpha-crystallin fraction; this is also evident in the fractionation of amphibian crystallins but is not common in the case of higher classes of vertebrates. The circular dichroism spectra indicate a predominant beta-sheet structure in all three fractions, albeit with some contribution of alpha-helical structure in the gamma-crystallin, the amino acid composition of which bears a resemblance to that of squid crystallin. Sequence comparison of carp gamma-crystallin with frog and calf gamma-crystallins indicates a high degree of homology in their N-terminal segments despite the dissimilarity of amino acid compositions and weak immunological cross-reactivity. PMID- 3110142 TI - Autophosphorylation of Ca2+/calmodulin-dependent protein kinase II. Effects on total and Ca2+-independent activities and kinetic parameters. AB - Incubation of purified rat brain Ca2+/calmodulin-dependent protein kinase II for 2 min in the presence of Ca2+, calmodulin (CaM), Mg2+, and ATP converted the kinase from a completely Ca2+-dependent kinase to a substantially Ca2+ independent form with little loss of total activity. Subsequent addition of EGTA to the autophosphorylation reaction enhanced further autophosphorylation of the kinase which was associated with a suppression of total kinase activity to the Ca2+-independent value. Protein phosphatase 1 rapidly increased the suppressed total activity back to the control value and slowly decreased the Ca2+ independent activity. Kinetic analysis showed that the kinase not previously autophosphorylated had a Km for the synthetic peptide syntide-2 of 7 microM and Vmax of 9.8 mumol/min/mg when assayed in the presence of Ca2+ and CaM. The partially Ca2+-independent species, assayed in the presence of EGTA, had a Km of 21 microM and Vmax of 6.0. In the presence of Ca2+ and CaM the Km decreased and the Vmax increased to approximately control nonphosphorylated values. The completely Ca2+-independent form generated by sequential autophosphorylation first in the presence of Ca2+ and then EGTA had similar kinetic parameters to the partially independent species when assayed in the presence of EGTA, but addition of Ca2+ and CaM (up to 1 mg/ml) had little effect. These results suggest that separate autophosphorylation sites in the Ca2+/CaM-dependent protein kinase II are associated with formation of Ca2+-independent activity and suppression of total activity. PMID- 3110143 TI - Identification of a lysyl residue in antithrombin which is essential for heparin binding. AB - Identification of lysyl residue(s) in human plasma antithrombin required for binding of heparin was approached using chemical modification with the amino group reagent pyridoxal 5'-phosphate. Modification of antithrombin with limiting amounts of reagent yields an average incorporation of the phosphopyridoxyl label into 1 lysine/protein molecule (Pecon, J. M., and Blackburn, M. N. (1984) J. Biol. Chem. 259, 935-938). Fractionation of the labeled antithrombin by affinity chromatography on heparin-Sepharose separated a phosphopyridoxylated antithrombin species devoid of heparin binding from modified protein which retained affinity for heparin. To generate peptide maps of the two antithrombin species, the proteins were reductively denatured, S-carboxymethylated, and digested with trypsin. Fractionation of the tryptic digests by reverse-phase high performance liquid chromatography indicated one peak in the chromatogram of the non-heparin binding species to be clearly different when compared to the chromatogram of the heparin-binding species. The sequence of the unique peptide, determined by automated Edman degradation, was Thr-Ser-Asp-Gln-Ile-His-Phe-Phe-Phe-Ala-Lys-Leu Asn-Cys-Arg. This peptide corresponds to a tryptic fragment including residues 115-129 in the sequence of antithrombin, with the modified residue identified as Lys-125. Additionally, phosphopyridoxylation of antithrombin in the presence of added heparin indicated that several other lysyl residues were "protected" from modification. Identification of this critical lysine for heparin binding strongly supports previous data which indicate that the heparin-binding domain of antithrombin is located at the NH2 terminus within one of the disulfide cross linked loops of the protein. PMID- 3110144 TI - Ammonium sulfate modifies adenylate cyclase and the chemotactic receptor of Dictyostelium discoideum. Evidence for a G protein effect. AB - (NH4)2SO4 was found to activate adenylate cyclase in Dictyostelium discoideum membranes. The effect of (NH4)2SO4 on the enzyme was observed after pretreatment of membranes but could not be observed if the salt was added to the assay mixture. Activation was seen when membranes were pretreated with 0.16 M (NH4)2SO4 and was maximal at 0.6-1.0 M. The maximal activation of the enzyme was observed within 3 min of pretreatment and was not readily reversible. The effect was specific for the NH+4 ion since pretreatment of membranes with other NH+4 salts could activate the enzyme, whereas pretreatment with NaCl or KCl could not. Pretreatment of plasma membranes with (NH4)2SO4 eliminated the sensitivity of the enzyme to the inhibitory effect of guanine nucleotides. (NH4)2SO4 pretreatment also significantly attenuated the inhibition by guanine nucleotides of cAMP binding to its plasma membrane receptor. The effect of (NH4)2SO4 on GTP inhibition of cAMP binding to its receptor was even more dramatic when the salt was present in the binding assay. (NH4)2SO4 also increased the ADP-ribosylation by cholera toxin of a 39,000-Da membrane protein. The data support the hypothesis that (NH4)2SO4-induced changes in adenylate cyclase and the cAMP receptor are due to an alteration of a putative G protein. PMID- 3110145 TI - Acetylcholine stimulates selective liberation and re-esterification of arachidonate and accumulation of inositol phosphates and glycerophosphoinositol in C62B glioma cells. AB - Glioma C62B cells, incubated for 18 h with either an unsaturated (arachidonate or oleate) or saturated (palmitate or stearate) radioactive fatty acid, incorporated label into most species of cellular glycerolipids. Treatment of prelabeled C62B cells with 1 mM acetylcholine (ACh) resulted in an accumulation of radioactive phosphatidate irrespective of which fatty acid was used as a label. However, only in cells prelabeled with unsaturated fatty acids were increases in radioactive fatty acids observed. When exogenous radioactive arachidonate was added to C62B cells in the presence of 1 mM ACh, there was a rapid, selective, and transiently enhanced incorporation of label (several times the control) into phosphatidylinositol (PI). The ACh-enhanced incorporation into PI was not preceded by enhanced incorporation of label into sn-1,2-diacylglycerol or phosphatidate but was followed by an increased labeling of polyphosphoinositides. Similarly, incorporation of oleate into PI was enhanced by ACh. In contrast, ACh did not enhance the incorporation of label into any glycerolipids when saturated fatty acids were used. C62B cells, incubated with [2-3H]inositol for 18 h selectively incorporated label into phosphoinositides. Stimulation of [2 3H]inositol-labeled cells with 1 mM ACh in the presence of 25 mM LiCl resulted in a rapid accumulation of radioactive inositol phosphates (mono-, bis-, and trisphosphates) and glycerophosphoinositol. The accumulation of inositol trisphosphates preceded that of inositol monophosphate and glycerophosphoinositol, while the accumulation of glycerophosphoinositol paralleled the time required for the ACh-stimulated esterification of arachidonate. These results suggest that ACh stimulates activation of a phospholipase C in C62B cells and release of 1,4,5-inositol trisphosphate. There is subsequent activation of phospholipase A2, which in turn liberates arachidonate from PI. The resulting lyso PI is either rapidly reesterified with unsaturated fatty acid to resynthesize PI, or further deacylated to yield glycerophosphoinositol. PMID- 3110146 TI - A new GTP-binding protein in differentiated human leukemic (HL-60) cells serving as the specific substrate of islet-activating protein, pertussis toxin. AB - A GTP-binding protein serving as the specific substrate of islet-activating protein (IAP), pertussis toxin, was partially purified from human leukemic (HL 60) cells that had been differentiated into neutrophil type. The partially purified protein, referred to as GHL, predominantly consisted of at least two polypeptides with molecular masses of 40,000 daltons (alpha) and 36,000 or 35,000 daltons (beta). The structure was similar to Gi or Go previously purified from rat brain as an alpha beta gamma-heterotrimeric IAP substrate (Katada, T., Oinuma, M., and Ui, M. (1986) J. Biol. Chem. 261, 8182-8191), although the existence of the gamma of GHL was unclear. The 40,000-dalton polypeptide contained the site for IAP-catalyzed ADP-ribosylation and the binding site for guanine nucleotide with a high affinity. The 36,000- and 35,000-dalton polypeptides were cross-reacted with the affinity-purified antibody raised against the beta of brain Gi and Go. Limited proteolysis with trypsin and immunoblot analyses with the use of the affinity-purified antibodies raised against the alpha of brain Gi or Go indicated that the alpha of GHL was different from the alpha of Gi or Go. Kinetics of guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) binding to GHL was also quite different from that to brain Gi or Go. Incubation of GHL with GTP gamma S resulted in a resolution into GTP gamma S bound alpha and beta(gamma) thus purified had abilities to inhibit a membrane bound adenylate cyclase activity and to associate with the alpha of brain IAP substrate in a fashion similar to the beta gamma of brain IAP substrates, suggesting that there were no significant differences in the biological activities between the beta(gamma) of GHL and those of Gi or Go. Physiological roles of the new GTP-binding protein, GHL, purified from the neutrophil-like cells in receptor-mediated signal transduction are discussed. PMID- 3110147 TI - A major factor VIII binding domain resides within the amino-terminal 272 amino acid residues of von Willebrand factor. AB - We have identified a Factor VIII (FVIII) binding domain residing within the amino terminal 272 amino acid residues of the mature von Willebrand Factor (vWF) subunit. Two-dimensional crossed immunoelectrophoresis showed direct binding of purified human FVIII to purified human vWF. After proteolytic digestion of vWF with Staphylococcus aureus V8 protease (SP), FVIII binding was seen only with the amino-terminal SP fragment III and not with the carboxyl-terminal SP fragment II. A monoclonal anti-vWF antibody (C3) partially blocked FVIII binding to vWF and SP fragment III. FVIII also bound to vWF which had been adsorbed to polystyrene beads. This binding was inhibited in a dose-dependent manner by whole vWF, SP fragment III, and by monoclonal antibody C3. Binding could not be inhibited by SP fragment I, which contains the middle portion of the vWF molecule, or by reduced and alkylated whole vWF. SP fragment II caused only minimal inhibition. Trypsin cleavage of SP fragment III produced a monomeric 35-kDa fragment containing the amino-terminal 272 amino acid residues of vWF. This fragment reacted with monoclonal antibody C3 and inhibited the binding of FVIII to vWF in a dose dependent manner. These studies demonstrate that a major FVIII binding site resides within the amino-terminal 272 amino acid residues of vWF. PMID- 3110148 TI - Correlation between thrombin-induced prostacyclin production and inositol trisphosphate and cytosolic free calcium levels in cultured human endothelial cells. AB - Cultured human umbilical vein endothelial cells (HUVEC) stimulated with thrombin are known to synthesize prostacyclin at least in part from arachidonate released by phospholipase A2, an enzyme directly activated by calcium. In this study, thrombin stimulation of Quin 2-loaded HUVEC caused rapid and dose-dependent rises in inositol trisphosphate (IP3) and cytosolic free calcium (Ca2+i) levels which preceded a similarly dose-dependent rise in prostacyclin production measured as 6 ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) by radioimmunoassay (ED50 = 0.6 0.7 units/ml for all three effects). Thrombin induced these effects in the absence of extracellular calcium (EGTA) or in the presence of either 8-bromo-cAMP or the calmodulin inhibitor W7. Thrombin inactivated with either diisopropyl fluorophosphate or D-Phe-Pro-Arg-chloromethyl ketone was inactive. In contrast, Quin 2-loaded cultured bovine aortic endothelial cells failed to respond to thrombin, although stimulation with trypsin elevated IP3 and Ca2+i levels and increased 6-keto-PGF1 alpha production. Restimulation of HUVEC with thrombin or histamine 5 min after an initial stimulation with thrombin (2 units/ml for 5 min) failed to induce a second rise in either IP3 or Ca2+i levels or further production of 6-keto-PGF1 alpha, whereas restimulation with ionomycin in the presence or absence of extracellular calcium elevated Ca2+i levels and induced further 6-keto-PGF1 alpha production. However, if the initial stimulation with thrombin was terminated by addition of D-Phe-Pro-Arg-chloromethyl ketone within 10-60 s, restimulation with a second dose of thrombin induced second rises in both IP3 and Ca2+i levels and additional 6-keto-PGF1 alpha production that were greatest when the initial thrombin stimulus was briefest. These results are consistent with the conclusion that IP3 acts as a second messenger by which thrombin elevates Ca2+i levels and initiates prostacyclin synthesis in HUVEC and that in vivo endothelial cells may be stimulated multiple times to synthesize prostacyclin if each period of stimulation is brief. PMID- 3110150 TI - Kinetics of binding of macrolides, lincosamides, and synergimycins to ribosomes. AB - The synergistic effect of type A (virginiamycin M (VM)) and type B (virginiamycin S (VS)) synergimycins and their antagonistic effect against erythromycin (a 14 membered macrolide) for binding to the large ribosomal subunit (50 S) have been related. This investigation has now been extended to 16-membered macrolides (leucomycin A3 and spiramycin) and to lincosamides (lincomycin). A dissociation of VS-ribosome complexes was induced as well by 16-membered macrolides as by lincosamides. The observed dissociation rate constant of VS-ribosome complexes was identified with the kappa-vs in the case of 16-membered macrolides, but linearly related to lincomycin concentration, suggesting a direct binding of the latter antibiotic to VS-ribosome complexes and the triggering of a conformational change of particles entailing VS release. Two different mechanisms were also involved in the VM-promoted reassociation to ribosomes of VS previously displaced by either macrolides or lincosamides. By binding to lincosamide-ribosome complexes, VM induced a conformational change of ribosomes resulting in higher affinity for VS and lower affinity for lincosamides. On the contrary, an incompatibility for a simultaneous binding of VM and 16-membered macrolides to ribosomes was observed. These results have been interpreted by postulating specific (nonoverlapping) and aspecific (overlapping) antibiotic binding sites at the peptidyltransferase domain. All the kinetic constants of five antibiotic families (type A and B synergimycins, 14- and 16-membered macrolides, and lincosamides) and a topological model of peptidyltransferase are presently available. PMID- 3110149 TI - Effects of amiloride analogues on Na+ transport in toad bladder membrane vesicles. Evidence for two electrogenic transporters with different affinities toward pyrazinecarboxamides. AB - Most of the electrical potential-driven 22Na+ uptake in toad bladder membrane vesicles can be blocked by the diuretic amiloride. Analysis of the amiloride inhibition curve indicates the presence of two pathways with low and high affinities to the diuretic (Garty, H. (1984) J. Membr. Biol. 82, 269-279). The selectivity of these pathways to amiloride was explored by comparing the inhibition curve of this diuretic with those of 10 of its structural analogues. The relative potencies of various amiloride-like compounds as blockers of the flux component with high affinity to amiloride were in good agreement with the structure-activity relationships elucidated from transepithelial short-circuit current measurements. Thus, this pathway is most probably the apical Na+-specific channel. The other pathway with lower affinity to the diuretic was relatively insensitive to modifications of the amiloride molecule, and the structure activity relationships measured for the inhibition of this pathway were different from those reported for any other amiloride-blockable process. Other experiments have established that the Na+ flux with low affinity to amiloride is electrogenic and is not mediated by a Na+/H+ or Na+/Ca2+ exchanger, Na+-hexose cotransporter, or the Na+/K+-ATPase. The data indicate that tracer flux measurements in toad bladder membrane vesicles monitor, in addition to the well-characterized apical Na+ channels, another amiloride-blockable electrogenic Na+ transporter. This pathway could be responsible for the basolateral amiloride-blockable Na+ conductance recently observed in nystatin-treated bladders (Garty, H., Warncke, J., and Lindemann, B. (1987) J. Membr. Biol. 95, 91-103). PMID- 3110152 TI - Biosynthesis and metabolism of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine in rat glomerular mesangial cells. AB - The ability of rat mesangial cells to synthesize 1-O-alkyl-2-acetyl-sn-glycero-3 phosphocholine (1-O-alkyl-2-acetyl-GPC), also known as platelet activating factor (PAF), was studied in mesangial cell cultures originating from isolated rat glomeruli. In response to the phospholipase A2 agonist A23187 mesangial cells synthesized PAF primarily via an acetyltransferase utilizing either [3H]lyso-PAF or [3H]acetate/[3H]acetyl-CoA substrates. The major PAF species synthesized was 1 O-hexadecyl-2-acetyl-GPC. PAF was also synthesized from 1-O-[3H]alkyl-2-acetyl-sn 3-glycerol, indicating the presence of a CDP-cholinephosphotransferase. Mesangial cells incorporated [3H]lyso-PAF to 1-O-[3H]alkyl-2-acyl-GPC. Subsequent stimulation with A23187 (2 microM) resulted in formation and release of [3H]PAF following 3 h, and this was associated with concomitant decrements in intracellular 1-O-[3H]alkyl-2-acyl-GPC and [3H]lyso-PAF levels, indicating a precursor-product relationship among these alkyl ether lipids. Mesangial cells rapidly converted exogenous [3H]PAF to [3H]lyso-PAF and 1-O-[3H]alkyl-2-acyl-GPC, and this process was inhibited by diisopropyl fluorophosphate (10 microM). The demonstration of PAF activation-inactivation pathways in mesangial cells may be of importance in regulating their function and in glomerular injury. PMID- 3110151 TI - Secretion of apolipoprotein A-I in lipoprotein particles following transfection of the human apolipoprotein A-I gene into 3T3 cells. AB - Apolipoprotein A-I (apoA-I) is the major protein constituent of plasma high density lipoproteins (HDL). To examine apoA-I processing and secretion, the human apoA-I gene (2.2-kilobase PstI-PstI fragment) linked to the mouse metallothionein promoter was transfected by electroporation into NIH 3T3 fibroblasts along with the plasmid pSV2 neo, which confers neomycin resistance. Transfected cells were selected for neomycin resistance and screened for the ability to produce apoA-I by enzyme-linked immunosorbent assay. In the absence of lipids in the medium, selected 3T3 cells secreted apoA-I, mainly in the proprotein form, at density greater than 1.25 g/ml. Following incubation of cells with lipids, and subsequent washing with lipid-free medium, apoA-I was recovered in the HDL region (1.063 1.21 g/ml) as well as in the 1.21 g/ml infranatant. Examination of the HDL fraction by electron microscopy revealed round particles, 10-21 nm in diameter. These data indicate that human apoA-I secreted by transfected 3T3 fibroblasts can assemble into lipoprotein particles under the appropriate conditions. PMID- 3110153 TI - Bicarbonate is a recycling substrate for cyanase. AB - Cyanase is an inducible enzyme in Escherichia coli that catalyzes bicarbonate dependent decomposition of cyanate to ammonia and bicarbonate. Previous studies provided evidence that carbamate is an initial product and that the kinetic mechanism is rapid equilibrium random (bicarbonate serving as substrate as opposed to activator); the following mechanism was proposed (Anderson, P. M. (1980) Biochemistry 19, 2282-2888; Anderson, P. M., and Little, R. M. (1986) Biochemistry 25, 1621-1626). (formula; see text) Direct evidence for this mechanism was obtained in this study by 1) determining whether CO2 or HCO3- serves as substrate and is formed as product, 2) identifying the products formed from [14C]HCO3- and [14C] OCN-, 3) identifying the products formed from [13C] HCO3- and [12C]OCN- in the presence of [18O]H2O, and 4) determining whether 18O from [18O]HCO3- is incorporated into CO2 derived from OCN-. Bicarbonate (not CO2) is the substrate. Carbon dioxide (not HCO3-) is produced in stoichiometric amounts from both HCO3- and OCN-. 18O from [18O]H2O is not incorporated into CO2 formed from either HCO3- or OCN-. Oxygen-18 from [18O]HCO3- is incorporated into CO2 derived from OCN-. These results support the above mechanism, indicating that decomposition of cyanate catalyzed by cyanase is not a hydrolysis reaction and that bicarbonate functions as a recycling substrate. PMID- 3110154 TI - Purification and characterization of pyruvate:NADP+ oxidoreductase in Euglena gracilis. AB - Pyruvate:NADP+ oxidoreductase was homogeneously purified from crude extract of Euglena gracilis. The Mr of the enzyme was estimated to be 309,000 by gel filtration. The enzyme migrated as a single protein band with Mr of 166,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that the enzyme consists of two identical polypeptides. The absorption spectrum of the native enzyme exhibited maxima at 278, 380, and 430 nm, and a broad shoulder was observed around 480 nm; the maximum at 430 nm was eliminated by reduction of the enzyme with dithionite. Reduction of the enzyme with pyruvate and CoA and reoxidation with NADP+ were proved from changes of absorption spectra. The enzyme contained 2 molecules of FAD and 8 molecules of iron. It was also indicated that the enzyme was thiamine pyrophosphate-dependent. The enzyme was oxygen-sensitive, and the reaction was affected by the presence of oxygen. Pyruvate was the most active substrate, but the enzyme was slightly active for 2-oxobutyrate, 3 hydroxypyruvate, and oxalacetate, but not for glyoxylate and 2-oxoglutarate. The native electron acceptor was NADP+, whereas NAD+ was completely inactive. Methyl viologen, benzyl viologen, FAD, and FMN were utilized as artificial electron acceptors, whereas spinach and Clostridium ferredoxins were inactive. Pyruvate synthesis by reductive carboxylation of acetyl-CoA with NADPH as the electron donor occurred by the reverse reaction of the enzyme. The enzyme also catalyzed a pyruvate-CO2 exchange reaction and electron-transfer reaction from NADPH to other electron acceptors like methyl viologen. These results indicate that pyruvate:NADP+ oxidoreductase in E. gracilis is clearly distinct from either the pyruvate dehydrogenase multienzyme complex or pyruvate:ferredoxin oxidoreductase. PMID- 3110155 TI - The cyanogenic substrate for horseradish peroxidase is a conjugated enamine. AB - We identify the cyanogenic substrate for horseradish peroxidase (HRP) as a conjugated enamine and explore this unusual reaction using alpha-aminocinnamate (RH) as follows. 1) HRP catalyzes the oxidation of RH by O2 (and its peroxidation by H2O2 to form R-R) to produce, simultaneously, CN- and benzaldehyde cyanohydrin. 2) RH is transient and must be generated in situ. The properties of the cyanogenic reaction of HRP are independent of the method of preparation of RH (whether this be condensation of NH3 with phenylpyruvate, enzymatic hydrolysis of glycyldehydrophenylalanine, or oxidation of L-phenylalanine by L-amino acid oxidase). 3) The oxidation of RH is a free radical chain reaction initiated by HRP Compounds I and II (I (or II) + RH----R. + II (or HRP], propagated by RO2. (R. + O2----RO2., RO2. + RH----R. + RO2H), and terminated by recombination reactions such as 2R.----R2 and RO2.----R' + HO2. followed by R. + HO2.----RH + O2. KMnO4 and K3Fe(CN)6 can substitute for HRP. 4) The proximal precursor of CN- and cyanohydrin is postulated to be RO2H (phi-CH(-O2H)-CCO2-(= NH]. These results explain why cyanide is generated from the synergistic action of HRP and L-amino acid oxidase on aromatic L-amino acids and O2 and suggest that the requirement for a beta-aryl substituent on the enamine originates in the reaction of RH with HRP, or of R with O2, rather than the imine/enamine tautomerization of the L amino acid oxidase product. PMID- 3110156 TI - Identification of a new GTP-binding protein. A Mr = 43,000 substrate for pertussis toxin. AB - In purified preparations of human erythrocyte GTP-binding proteins, we have identified a new substrate for pertussis toxin, which has an apparent molecular mass of 43 kDa by silver and Coomassie Blue staining. Pertussis toxin-catalyzed ADP-ribosylation of the 43-kDa protein is inhibited by Mg2+ ion and this inhibition is relieved by the co-addition of micromolar amounts of guanine nucleotides. GTP affects the ADP-ribosylation with a K value of 0.8 microM. Addition of a 10-fold molar excess of purified beta gamma subunits (Mr = 35,000 beta; and Mr = 7,000 gamma) of other GTP-binding proteins results in a significant decrease in the pertussis toxin-mediated ADP-ribosylation of the 43 kDa protein. Treatment of the GTP-binding proteins with guanosine 5'-O (thiotriphosphate) and 50 mM MgCl2 resulted in shifting of the 43-kDa protein from 4 S to 2 S on sucrose density gradients. Immunoblotting analysis of the 43 kDa protein with the antiserum A-569, raised against a peptide whose sequence is found in the alpha subunits of all of the known GTP-binding, signal-transducing proteins (Mumby, S. M., Kahn, R. A., Manning, D. R., and Gilman, A. G. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 265-259) showed that the 43-kDa protein is specifically recognized by the common peptide antiserum. A pertussis toxin substrate of similar molecular weight was observed in human erythrocyte membranes, bovine brain membranes, membranes made from the pituitary cell line GH4C1, in partially purified GTP-binding protein preparations of rat liver, and in human neutrophil membranes. Treatment of neutrophils with pertussis toxin prior to preparation of the membranes resulted in abolishment of the radiolabeling of this protein. From these data, we conclude that we have found a new pertussis toxin substrate that is a likely GTP-binding protein. PMID- 3110157 TI - The GTP-binding protein of rod outer segments. II. An essential role for Mg2+ in signal amplification. AB - The role of Mg2+ in the GTP hydrolytic cycle was investigated by using purified subunits (G alpha and G beta, gamma) of the GTP-binding protein isolated from Bufo marinus rod outer segments (ROS). Mg2+ markedly stimulated the rate of GTP and guanosine-5'-O-(3-thiotriphosphate) (GTP gamma-s) binding to G alpha. This effect was especially striking in the presence of very small quantities of illuminated ROS disc membranes. GTP hydrolysis could occur in the absence of Mg2+, and Mg2+ increased the rate of GTP hydrolysis only about 50%. These data indicate that Mg2+ plays a fundamental role in amplification of the photon signal by markedly stimulating the rate of formation of GTP X G alpha complexes by very small amounts of illuminated rhodopsin while producing only a modest increase in the rate of GTP hydrolysis. Following hydrolysis of GTP, GDP X G alpha could reassociate with illuminated or unilluminated ROS disc membranes in the presence or absence of Mg2+. In the absence of guanine nucleotides, release of GDP from G alpha bound to illuminated disc membranes was detected in the presence or absence of Mg2+. Moreover, Mg2+ did not affect the rate of GDP release from membrane bound G alpha. Illumination of B. marinus crude ROS disc membrane preparations markedly reduced pertussis toxin-mediated ADP-ribosylation of a 39,000 Mr (G alpha) protein in the presence but not in the absence, of Mg2+. Moreover, extensive dialysis of illuminated (but not unilluminated) crude ROS disc membranes against a Mg2+-containing buffer caused a marked reduction in the subsequent ADP-ribosylation of G alpha, even when Mg2+ was not present during the ADP-ribosylation step. This reduction was reversed by the addition of GDP or a GDP analogue (but not GMP or hydrolysis-resistant GTP analogues) during the ADP ribosylation step. Dialysis of crude ROS disc membrane preparations (illuminated or unilluminated) against a Mg2+ -free buffer did not reduce the subsequent ADP ribosylation of G alpha. These data indicate that Mg2+, in the presence of photolysed rhodopsin, can stimulate the release of GDP from crude preparations of ROS disc membranes. Four lines of evidence suggest that G alpha and G beta, gamma have Mg2+-binding site(s). When stored at 4 degrees C, in the absence of glycerol, G beta, gamma was more stable in the absence than in the presence of Mg2+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3110158 TI - The bifunctional aminoadipic semialdehyde synthase in lysine degradation. Separation of reductase and dehydrogenase domains by limited proteolysis and column chromatography. AB - The mammalian aminoadipic semialdehyde synthase is a bifunctional enzyme that catalyzes the first two sequential steps in lysine degradation in the major saccharopine pathway (Markovitz, P. J., Chuang, D. T., and Cox, R. P. (1984) J. Biol. Chem. 259, 11643-11646). We show here that limited proteolysis of the highly purified synthase from bovine liver with elastase, chymotrypsin, and papain resulted in separation of lysine-ketoglutarate reductase and saccharopine dehydrogenase activities as judged by activity stainings of the polyacrylamide gel. Enzyme assays showed no loss of the two activities after digestions with these proteases. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis disclosed the presence of two limit polypeptides in the elastolytic digests, i.e. fragment A (Mr = 62,700) and fragment B (Mr = 49,200). These fragments were apparently derived from the same polypeptide (Mr = 115,000) of the parent synthase. The reductase and dehydrogenase activities of the elastase-digested synthase were completely resolved by DEAE-Bio-Gel column chromatography. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that fragment A and fragment B were associated with reductase and dehydrogenase activities, respectively. The bovine synthase showed Mr = 420,000 in sedimentation equilibrium, confirming a tetrameric structure for the enzyme. The above results establish that the reductase and dehydrogenase domains of the aminoadipic semialdehyde synthase are separately folded and functionally independent of each other. PMID- 3110159 TI - Glycogen phosphorylase in Dictyostelium. Developmental regulation of two forms and their physical and kinetic properties. AB - A key step in the cellular differentiation of Dictyostelium is the degradation of glycogen to provide the precursors for synthesis of the structural end products of development. We have found that the enzyme that initiates this degradative pathway, glycogen phosphorylase (1,4-alpha-D-glucan:orthophosphate alpha-glucosyl transferase, EC 2.4.1.1), is developmentally regulated and exists as two forms. During the time course of development, a previously undescribed activity, the "b" form, decreases, whereas that of the "a" form increases. The b form is inactive unless 5'-AMP is included in the reaction mixture. The mechanism of activation by 5'-AMP is by a 40-fold increase in the affinity of the phosphorylase for its substrates. Both forms were purified to homogeneity. They have identical subunit molecular weights of 90,000 and both exist as a dimer under non-denaturing conditions. The two forms are also identical with respect to salt inhibition, optimum temperature for activity, and pH optimum. They differ in their elution from DE52-cellulose, affinity constants, thermal stability, affinity for 5'-AMP Sepharose, and their peptide maps. Attempts to demonstrate interconversion of the two activities by a kinase-directed phosphorylation have been unsuccessful. We report here on the existence, the developmental regulation, the purification to homogeneity, and some of the physical and kinetic properties of both the 5'-AMP dependent and -independent forms of the enzyme. PMID- 3110160 TI - Interaction between NAD-dependent isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase complex, and NADH:ubiquinone oxidoreductase. AB - Interaction between the alpha-ketoglutarate dehydrogenase complex and NAD+ dependent isocitrate dehydrogenase was detected with a variety of techniques including polyethylene glycol precipitation, ultracentrifugation, and centrifugal gel filtration on a Sepharose 6B column. The interaction was specific in that citrate synthase, cytosolic malate dehydrogenase, and NADP-dependent isocitrate dehydrogenase did not interact with alpha-ketoglutarate dehydrogenase complex. The interaction was not inhibited by either 0.1 M KCl or 0.4 M (NH4)2SO4, but was completely prevented by 5% glycerol. A new method for the preparation of NADH: ubiquinone oxidoreductase resulted in an enzyme having a protein subunit composition similar to that of classical complex I preparation. Evidence is given for the existence of ternary complexes containing NADH:ubiquinone oxidoreductase alpha-ketoglutarate dehydrogenase complex-NAD-dependent isocitrate dehydrogenase and NADH: ubiquinone oxidoreductase-alpha-ketoglutarate dehydrogenase complex succinate thiokinase. These data suggest that a part of the citric acid cycle may be located in the vicinity of NADH: ubiquinone oxidoreductase. These complexes may facilitate the transport of metabolites among these enzymes without their equilibrating with the whole compartment. PMID- 3110161 TI - Ionomycin inhibits thyrotropin-releasing hormone-induced translocation of protein kinase C in GH4C1 pituitary cells. AB - Thyrotropin-releasing hormone (TRH) induces rapid and transient conversion of protein kinase C (Ca2+/phospholipid-dependent enzyme) from a soluble to a particulate-bound form in GH4C1 rat pituitary cells. Ionomycin (200 nM), a calcium ionophore, had no effect by itself on the subcellular distribution of protein kinase C. However, pretreatment of the cells with 200 nM ionomycin inhibited by greater than 50% the ability of TRH to cause translocation of protein kinase C from the cytosol to the particulate cell fraction. Inhibition by ionomycin required that the cells be incubated with the ionophore for at least 10 s before TRH addition. Ionomycin pretreatment did not alter the kinetics of TRH induced protein kinase C redistribution. Incubation of the cells with 43 mM potassium prior to TRH addition almost completely reversed the inhibition induced by ionomycin. We propose that the mechanism by which ionomycin attenuates TRH action on protein kinase C may involve the capacity of the ionophore to empty the intracellular calcium reservoir which normally releases calcium into the cytosol in response to TRH. Our result provides evidence that the rise in intracellular calcium, which accompanies diacylglycerol formation following TRH action on polyphosphatidylinositide hydrolysis, may be required to achieve maximal conversion of protein kinase C to its presumed active, membrane-bound form in these cells. PMID- 3110162 TI - Rat liver UDP-glucuronosyltransferase. Identification of cDNAs encoding two enzymes which glucuronidate testosterone, dihydrotestosterone, and beta estradiol. AB - The 1818-base pairs cDNA encoding a form of rat liver UDP-glucuronosyltransferase designated UDP-GTr-3 was sequenced and found to encode a protein of 530 amino acids (Mr = 60,522). Characteristic sequences include a signal peptide and a carboxyl-terminal transmembrane anchoring region. There were no potential asparagine-linked glycosylation sites. Transcription and translation of the cDNA in vitro showed that the encoded protein was synthesized as a precursor and was cleaved when dog pancreatic microsomes were present during translation. Cleaved UDPGTr-3 was intrinsically associated with the added membranes, whereas uncleaved polypeptide remained in the supernatant upon fractionation of the translation mixture. UDPGTr-3 and a related phenobarbital-inducible form of UDP glucuronosyltransferase (designated UDPGTr-2) were both expressed in COS cells and their capacities to glucuronidate 13 commonly used substrates were analyzed. Whereas both enzymes glucuronidated the endogenous steroids testosterone, dihydrotestosterone, and beta-estradiol, only UDPGTr-2 was active towards the foreign chemical substrates, chloramphenicol, 4-hydroxybiphenyl, and 4 methylumbelliferone. Neither enzyme was active towards estrone, androsterone and substrates typical of 3-methylcholanthrene-inducible forms of UDP glucuronosyltransferase. Steady-state levels of UDPGTr-3 and UDPGTr-2 mRNAs were highest in the liver and were barely detectable in kidney, lung, testis, and small intestinal mucosa. These data show that at least two forms of UDP glucuronosyltransferase found predominantly in the liver have evolved to glucuronidate the same endogenous steroid substrates and that the phenobarbital inducible form also has some activity towards foreign compounds. PMID- 3110163 TI - O-linked N-acetylglucosamine is attached to proteins of the nuclear pore. Evidence for cytoplasmic and nucleoplasmic glycoproteins. AB - Glycoproteins bearing a single N-acetylglucosamine (GlcNAc) residue attached by an O-glycosidic linkage to the polypeptide chain (Holt, G. D., and Hart, G. W. (1986) J. Biol. Chem. 261, 8049-8057) have been found to be enriched in the nuclear and soluble fractions of rat liver. Our goal was to determine the localization and membrane topography of proteins bearing O-linked GlcNAc using galactosyltransferase and wheat germ agglutinin (WGA) as membrane-impermeant probes. Latency of the enzyme mannose-6-phosphatase was used to quantitatively confirm the intactness of the nuclear envelope during incubations with galactosyltransferase or WGA. The O-linked GlcNAc residues of nuclei were fully accessible to modification by galactosyltransferase under conditions where the nuclear envelope mannose-6-phosphatase was 70% latent. Addition of detergent destroyed the permeability barrier but did not increase galactosylation of the O linked GlcnAc. The major polypeptides bearing O-linked GlcNAc residues on nuclei were peripheral rather than integral membrane proteins with apparent molecular masses ranging from 210 to 54 kDa. The proteins were also detected on sealed nuclei using conjugates of WGA. WGA-rhodamine labeled intact nuclei when examined by immunofluorescence; WGA-peroxidase was used to identify the nuclear glycoproteins after transfer to nitrocellulose. WGA-ferritin selectively labels the cytoplasmic and nucleoplasmic faces of the nuclear pore complex when examined by electron microscopy. Taken together, these data strongly suggest that proteins bearing cytoplasmically oriented O-linked GlcNAc are components of the nuclear pore complex, thereby raising the possibility that cytoplasmic and nucleoplasmic glycoproteins are involved in the assembly or functioning of the nuclear pore. PMID- 3110164 TI - Glutaraldehyde inactivated pertussis vaccine: a less histamine sensitizing vaccine. AB - The effects of different inactivating agents on the biological activity of the histamine sensitization factor of Bordetella pertussis toxin were examined. The agents were used for inactivation in the preparation of whole cell pertussis suspension. The histamine sensitizing activity was reduced to 36.9-13.3% by treatment with glutaraldehyde, to about 50% by treatment with formaldehyde and by the acetone-II treatment, relative to the reduction by heat treatment. Treatment with thimerosal and the acetone-I treatment did not reduce the histamine sensitizing activity as the 50% histamine sensitizing doses of the heat inactivated pertussis preparation, the thimerosal inactivated pertussis preparation and the acetone-I treated pertussis preparation were very similar. Glutaraldehyde has thus been found to be a better inactivating agent for the preparation of a safe pertussis suspension as it considerably reduced the histamine sensitizing activity of pertussis toxin. PMID- 3110165 TI - Cross-union complicating fracture of the forearm. Part I: Adults. AB - The cases of twenty-eight adults who had cross-union as a complication of fractures of the forearm were analyzed according to a new classification system. Four cross-unions were Type 1 (distal intra-articular part of the radius and ulna); fourteen, Type 2 (middle third or non-articular part of the distal third of the radius and ulna); and ten, Type 3 (proximal third of the radius and ulna). Type-1 cross-union occurred rarely, but it developed most commonly after closed reduction of a fracture. Types 2 and 3 typically followed severe local trauma and delayed open reduction. Bone fragments left in the interosseous space and bone screws that broached the opposite part of the cortex were common findings. Seventeen cross-unions were excised. Three of the four Type-1, none of the ten Type-2, and two of three Type-3 cross-unions recurred. The results after excision of Type-2 cross-unions in our series were far better than other results that have been previously reported. PMID- 3110166 TI - Cross-union complicating fracture of the forearm. Part II: Children. AB - Cross-union is a rare complication of fractures of the forearm in children. Of the ten cross-unions reported in this series, four were Type 2 (middle third or non-articular part of the distal third of the radius and ulna) and six were Type 3 (proximal third of the forearm). There were no Type-1 (intra-articular part of the distal third of the radius and ulna) cross-unions. As in adults, the Type-2 cross-unions followed a high-energy injury. Three of the four Type-2 cross-unions were excised; one of them recurred. Type-3 cross-unions occurred equally after closed or open reduction of a fracture. Three patients with a Type-3 cross-union had excision of the radial head. The only patient who did not have a recurrence of the cross-union also underwent insertion of a prosthesis for the radial head. The results after resection of a cross-union appear to be better in the adult than in the child, although the number of patients in this and other studies is too small to allow firm conclusions. PMID- 3110167 TI - Total hip arthroplasty for tuberculous coxarthrosis. AB - Forty-four total hip prostheses were implanted in thirty-eight patients who had tuberculous arthritis of the hip. The interval between active disease and total hip arthroplasty ranged from three months to forty-five years. The length of follow-up averaged 45.6 months (range, twenty-four to eighty-five months). Cultures of material and specimens of tissue that were taken intraoperatively were positive in four hips. The mean functional rating of the hip was 62 points preoperatively and 85 points at final follow-up. Thirty-one patients had a good result; one had to have a revision because of loosening of a component. Six patients had reactivation of the disease that was controlled satisfactorily by chemotherapy alone or in combination with debridement of sinus tracts without removal of the prosthesis. There was a major difference in the percentage of recurrences in patients who had inactive disease for less than ten years (six of fifteen patients) compared with those who had inactive disease for more than ten years (no patients). Total hip arthroplasty appears to be a safe procedure for patients who have quiescent tuberculosis as well as for patients who have active tuberculosis of the hip when there is no gross evidence of active infection. PMID- 3110168 TI - Laterally comminuted fracture-dislocation of the ankle. AB - Laterally comminuted fracture-dislocations of the ankle are highly unstable injuries in which anatomical reduction of the talus and restoration of fibular length and rotation are difficult. To our knowledge, no descriptions of the fracture pattern of these injuries and the surgical technique for treating them are available, and surgical results with this fracture have been disappointing. Discontinuity of the fibula as a result of comminution makes accurate assessment of fibular length and rotation impossible if the fibula is reduced first. Anatomical stabilization of the talus beneath the tibia is achieved by reduction and fixation of the medial malleolus. The fibular malleolus is then anatomically positioned in the lateral articular facet of the talus and fixed in this position. The osseous discontinuity of the fibula is grafted with bone. Clinical and radiographic results of the technique were highly satisfactory after a mean length of follow-up of thirty-four months. PMID- 3110169 TI - Potential DRG reimbursement vs actual cost of burn care. I. Patients with burns of less than 25% TBSA. PMID- 3110170 TI - Potential DRG reimbursement vs actual cost for burn care. II. Referral distance. PMID- 3110171 TI - Comparison of continuous and intermittent tube feedings in burned animals. PMID- 3110172 TI - Comparative study of hand cleansers used in hospitals: in vitro antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. PMID- 3110173 TI - Effects of the phorbolester TPA and of the ionophore A 23187 on phospholipase A2 and C activities in the mouse epidermal cell line HEL-30. AB - The 12-O-tetradecanoylphorbol-13-acetate (TPA)- or ionophore A 23187-induced release of 14C-arachidonic acid from prelabeled murine HEL-30 keratinocytes was studied in vitro. Starting 8 min after drug treatment, a linear increase in the arachidonic acid content in the extracellular medium was observed with a concomitant loss of label in cellular phosphatidylcholine and phosphatidylinositol, but not in phosphatidylethanolamine and phosphatidylserine. No increase in intracellular diacylglycerol and phosphatidic acid was observed. The TPA-induced arachidonic acid release was inhibited by fluocinolone acetonide. The results indicate a direct activation of phosphatidylcholine- and phosphatidylinositol-specific phospholipases A2 by TPA and A23187. Cells prelabeled with 3H-choline released choline, choline phosphate and CDP-choline upon TPA but not upon A 23187 treatment. This could indicate activation of a phospholipase C-type enzyme by the phorbol ester. However, concomitant generation of diacylglycerol and phosphatidic acid was not detected. PMID- 3110174 TI - Stimulation of arachidonic acid metabolism in rat peritoneal macrophages by thapsigargin, a non-(12-O-tetradecanoylphorbol-13-acetate) (TPA)-type tumor promoter. AB - The effects of thapsigargin, which is a histamine secretagogue and has recently been found to be a non-(12-O-tetradecanoylphorbol-13-acetate) (TPA)-type tumor promoter in two-stage carcinogenesis using mouse skin, on arachidonic acid metabolism in rat peritoneal macrophages were examined. The release of radioactivity from 3H arachidonic acid-labeled macrophages was increased at doses more than 10 ng/ml. Prostaglandin E2 production was also increased dose dependently without inducing prominent changes in cell morphology. The potency to stimulate prostaglandin E2 production by thapsigargin was stronger than that by TPA at a dose of 10 ng/ml when measured 6 h after the incubation. HPLC analysis revealed that thapsigargin stimulated the production of lipoxygenase products such as leukotriene B4 and 12-hydroxyeicosatetraenoic acid as well as cyclooxygenase products such as prostaglandin E2 and 6-keto prostaglandin F 1 alpha. Thapsigargin, an analogue of thapsigargin, also stimulated prostaglandin E2 production. The mechanism of the action of thapsigargin was discussed. It was confirmed that the tumor promoters are associated with the activity to stimulate arachidonic acid metabolism irrespective of their type, TPA-type or non-TPA-type. PMID- 3110175 TI - Establishment of murine macrophage hybridoma clones capable of acquiring tumoricidal activity upon activation with recombinant interferon-gamma and lipopolysaccharide. AB - Murine macrophage hybridoma clones were established by fusing glycogen-elicited peritoneal exudate cells (glycogen-PEC) derived from C3H/HeN mice and the hypoxanthine-aminopterin-thymidine-sensitive murine macrophage cell line, J774.3 2. The macrophage hybridomas were further screened for the capacity to acquire tumoricidal activity upon stimulation with lipopolysaccharide (LPS) and recombinant interferon-gamma (IFN-gamma) using murine mammary adenocarcinoma MM48 cells as targets, and three macrophage hybridoma clones, KM-1, KM-2, and KM-3, were established. With concomitant stimulation with LPS, IFN-gamma activated these hybridomas dose dependently to exhibit high tumoricidal activity, whereas single stimulation with either INF-gamma or LPS, even with higher concentrations, did not activate the macrophage hybridomas. This contrasted with the activation of glycogen-PEC for eliciting tumoricidal activity with a single stimulation with LPS (greater than 1 ng/ml) or IFN-gamma (greater than 10 IU/ml). Thus, the macrophage hybridoma clones established here represent inflammatory macrophages which require both IFN-gamma and LPS for their activation. PMID- 3110176 TI - Modulation of murine erythroleukemic cell differentiation by inhibitors of polyamine biosynthesis. AB - The differentiation of murine erythroleukemic cells induced by hexamethylene bisacetamide is shown to be differently affected by two inhibitors of polyamine biosynthesis. Methyl glyoxal bis(guanyl hydrazone) (inhibitor or S-adenosyl methionine decarboxylase) inhibited this differentiation process. By using a novel experiment protocol the inhibitory effect of this drug on the induced differentiation was dissociated from pleiotropic effects on cell growth. Methyl glyoxal bis(guanyl hydrazone) only inhibited the induced differentiation if present during the first 6 h of culture of the cells with the inducer. No effect on the induced differentiation was observed if the drug was added to the culture medium 6 h after the inducer. alpha-Difluoro methylornithine (inhibitor of ornithine decarboxylase) stimulated the differentiation of these cells. Polyamine analysis demonstrated that alpha-difluoro methylornithine increased the rapidity and the amplitude of the changes in intracellular polyamines associated with this induced differentiation. The presence of methyl glyoxal bis(guanyl hydrazone) during the first 3 h with the inducer was sufficient to produce opposing changes in the intracellular polyamines. These results suggest that changes in either intracellular polyamines or the activities of polyamine biosynthetic enzymes play a regulatory role in the differentiation process induced in murine erythroleukemic cells by hexamethylene bisacetamide. PMID- 3110177 TI - alpha 2HS glycoprotein is chemotactic for mononuclear phagocytes. AB - alpha 2HS glycoprotein is a normal constituent of plasma. It has a high affinity for hydroxyapatite and is concentrated in bone 100-fold greater than albumin, however its biological function in bone is not known. We have purified alpha 2HS from human plasma and examined it for evidence of chemotactic activity against human peripheral mononuclear cells, polymorphonuclear leucocytes and lymphocytes in Boyden chamber assays. We observed that the protein was chemotactic for mononuclear cells and that maximal cell migration occurred when its concentration in the lower compartment of Boyden chambers was 10(-10) M. Chemotaxis did not occur in the absence of a concentration gradient. In addition, cell migration was blocked when the cells were preincubated with 10(-10) M alpha 2HS or when the protein was preincubated with rabbit anti-human alpha 2HS glycoprotein IgG. Neither polymorphonuclear leucocytes, which are responsive to a wide range of chemoattractants, or peripheral lymphocytes exhibited directed migration to alpha 2HS in Boyden chamber assays. The glycoprotein appears therefore to act as a chemotaxin directed to monocyte recruitment, and we speculate that the protein may have an important role in monocyte recruitment to bone and possibly their subsequent fusion and differentiation into functional osteoclasts. PMID- 3110179 TI - Multiple drug use in an elderly man. PMID- 3110178 TI - Biological activity, binding, and metabolic fate of Ac-[Nle4, D-Phe7]alpha-MSH4 11NH2 with the F1 variant of B16 melanoma cells. AB - The alpha-MSH (alpha-melanocyte-stimulating hormone) agonist, Ac-[Nle4, D Phe7]alpha-MSH4-11NH2 (hereafter called ND4-11 alpha-MSH), is at least 10-fold more potent than alpha-MSH as a stimulus of tyrosinase activity in F1 variant cells of B16 melanoma. The binding to these cells during an incubation with 5 nM (3H)ND4-11 alpha-MSH at 37 degrees C is maximal at 0-30 min, 22 fmol/10(6) cells, but declines to 40% of this value at 4 hr. in the presence of 5 nM (3H)ND4-11 alpha-MSH at 37 degrees C, the acid soluble (cell surface) radioactivity decreased rapidly from 11.4 fmol/10(6) cells at 5 min to 4.6 fmol/10(6) cells at 4 hr. Chromatographic analysis of media and cellular samples revealed that there was no evidence of degradation of (3H)ND4-11 alpha-MSH in the medium but there was evidence of intracellular degradation of (3H)ND4-11 alpha-MSH. Ammonium chloride (10mM) resulted in an increase in acid resistant radioactivity (internalized hormone) at 4 hr. The binding to F1 variant cells during an incubation with 0.155 nM or 5 nM (3H)ND4-11 alpha-MSH at 4 degrees C was constant from 4 hr to 24 hr. Under these conditions, there was no time-dependent change in the acid soluble radioactivity from 4 to 24 hr. Scatchard analysis of (3H)ND4-11 alpha-MSH binding to F1 variant cells at 4 degrees C demonstrated that there were approximately 4500 receptors per cell and an association constant of 17.1 nM-1. These results are consistent with a process of (3H)ND4-11 alpha-MSH binding to its receptor followed by internalization of the receptor-hormone complex and then intracellular degradation of the hormone. PMID- 3110180 TI - Cardiac tamponade in a healthy young woman. PMID- 3110181 TI - Of pain, pain relief, and pain 'clinics'. PMID- 3110182 TI - Bowel obstruction in 'burned out' Crohn's. PMID- 3110183 TI - The quality of mercy is strained. PMID- 3110184 TI - Combined treatment approaches to soft tissue sarcomas. PMID- 3110185 TI - Genetic disease: an overview of current therapy. PMID- 3110186 TI - Alcoholic student on a beer and vomiting binge. PMID- 3110187 TI - The periodic health examination. PMID- 3110188 TI - Ovarian Ca management: controversial points. PMID- 3110189 TI - Six hundred sixty-six minus sixty. PMID- 3110190 TI - The arrhythmia that converted spontaneously in the ER. PMID- 3110191 TI - The MRC today: British science at the crossroads. Medical Research Council. PMID- 3110192 TI - Post hoc, ergo propter hoc. PMID- 3110193 TI - Current status of liver transplantation. PMID- 3110194 TI - Pauses in rhythm during antiarrhythmic therapy. PMID- 3110195 TI - Hypercalcemia: pathophysiology and treatment. PMID- 3110196 TI - Biomedical applications of thermospray liquid chromatography-mass spectrometry. AB - Thermospray liquid chromatography-mass spectrometry has been applied in the solution of a number of problems of biological and biomedical interest. These include the analysis of phenazines from the Gram negative bacterium Pseudomonas aeruginosa, steroids released by rat adrenals and eicosanoids generated by human inflammatory cells. The application of the technique to leukotrienes in blood is discussed. Isotopic labelling prior to analysis, to facilitate identification and structure elucidation is outlined with reference to the steroids. PMID- 3110197 TI - Microsample determination of diazepam and its three metabolites in serum by reversed-phase high-performance liquid chromatography. PMID- 3110198 TI - Morbidity during hospitalization: can we predict it? AB - Physicians use the concept of stability to estimate the likelihood that a patient will deteriorate during a hospitalization. To determine whether physicians can accurately predict a patient's risk of morbidity, 603 patients admitted to the medical service during a one month period were rated prospectively as to how stable they were. Overall, 15% of patients had deterioration of already compromised systems, while 17% had new complications, such as sepsis. Eight percent of patients had both. Twelve percent of stable patients experienced morbidity; 39% of the somewhat unstable and 61% of the most unstable. When all of the demographic and clinical variables were taken into account including the reason for admission and comorbid diseases, the residents' estimates of the patient's stability was the most significant predictor of morbidity (p less than 0.001). The judgment that a patient was stable had an 87% negative predictive accuracy, while the judgment unstable had a 46% positive predictive accuracy. PMID- 3110199 TI - A comparative cost analysis of terminal cancer care in home hospice patients and controls. AB - A comparison is made between the expenditure during the last 90 days of life on 98 terminal cancer patients cared for by a home based hospice service and that on matched patients dying without the home hospice service. The control patients were matched for site of primary cancer, age and sex. The individual records of both groups of patients were analyzed and costed. It was found that the costs of providing 24 hour comprehensive medical and nursing care at home to those dying of cancer and support for their families was no more expensive than traditional institutional care. PMID- 3110200 TI - Dexamethasone reduces the postcastration gonadotropin rise in women. AB - To investigate the influence of glucocorticoids on gonadotropin release in humans, we studied the effects of dexamethasone (DXM) administration on basal and GnRH-stimulated gonadotropin secretion in normal women after bilateral ovariectomy (OVR). From the 7th to the 14th day after OVR, 9 women received DXM (2.25 mg/day) and 13 women received placebo (control women). Plasma FSH and LH concentrations were measured before OVR and daily from the 7th to the 14th day after surgery. In addition, the FSH and LH responses to exogenous GnRH (10 micrograms, iv bolus dose) were determined in all DXM-treated women and in 5 control women on the 7th and 14th days after surgery. Plasma gonadotropin levels increased similarly in all women on the 7th day after OVR. DXM administration significantly limited (P less than 0.001) the progressive rise of basal LH and FSH levels from days 7 to 14. DXM treatment also blunted (P less than 0.005) the OVR-induced increase in the responsiveness of both LH and FSH to exogenous GnRH. These findings suggest that glucocorticoids inhibit the secretion of both gonadotropins at the pituitary level in ovariectomized women. PMID- 3110201 TI - Corticotropin-releasing hormone inhibits gonadotropin secretion in the ovariectomized rhesus monkey. AB - To evaluate whether the compromised gonadotropin secretion frequently occurring during stressful conditions in the primate may be related to an inhibitory action of CRH, the effects of ovine (oCRH) or human (hCRH) CRH on gonadotropin and cortisol secretion were studied in ovariectomized rhesus monkeys. LH secretion (assessed as area under the curve) decreased 35% and 21%, and cortisol increased 37% and 90%, 1-3 h after single iv injections of 200 and 500 micrograms oCRH, respectively (P less than 0.05 vs. pre-CRH control period; n = 4-7/dose). Single injections of 200 and 500 micrograms hCRH, respectively, resulted in 35% and 24% decreases in LH and 40% and 79% increases in cortisol secretion (P less than 0.05). Injections of 100 micrograms oCRH and hCRH elicited significant (P less than 0.05) increases in cortisol release (37% and 31%, respectively), but did not affect LH secretion. A 5-h infusion of hCRH (100 micrograms/h) reduced LH levels (23%, 49%, 59%, 61%, and 62% during the first through the fifth hour, respectively; P less than 0.05 for hours 2-5). FSH secretion also decreased during the hCRH infusion (26%, 33%, 42%, 46%, and 49% during the first through the fifth hour, respectively; P less than 0.05 for hours 3-5), while cortisol increased 76%. These data demonstrate that exogenous CRH administration results in inhibition of LH and FSH secretion in ovariectomized rhesus monkeys. These results are consistent with the hypothesis that elevated CRH levels could contribute to decreased LH and FSH secretion and, thus, disruption of reproduction function under conditions of stress in primates. PMID- 3110202 TI - Results of 1-year growth hormone (GH)-releasing hormone-(1-44) treatment on growth, somatomedin-C, and 24-hour GH secretion in six children with partial GH deficiency. AB - Six children with short stature and partial GH deficiency in response to two pharmacological tests received GHRH for 12 months (10 micrograms/kg X day, sc) each evening. Twenty-four-hour GH secretion was studied before and after 3 and 12 months of treatment, and GHRH tests (2 micrograms/kg, iv) were done before and after 6 months of treatment. Plasma somatomedin-C was measured before and after 1.5, 3, 6, 9, and 12 months of treatment. Statural growth was measured at 3-month intervals. Mean growth velocity increased from 4.2 to 8.6 cm/yr, with a good result in five children and no response in the other. The growth response was substantial during the first 3 months. It was maintained during the following 6 months, and then decreased during the last 3 months. The peak plasma GH level in response to GHRH increased from 34.5 +/- 14.2 (+/-SD) ng/mL before treatment to 47.8 +/- 3.4 ng/mL after 6 months of treatment. Twenty-four-hour GH secretion increased in all parameters at 3 months (maximum peak, area under the curve, integrated concentration, and number of peaks) and at 12 months (with the exception of the maximum peak). Nycthemeral secretory profiles became normal, with reappearance of secretory pulses in two children, slight increases in three children, and no change in one child. Plasma somatomedin-C levels rose from 0.8 +/- 0.3 U/mL before treatment to 2.0 +/- 1.0 U/mL at 3 months, then decreased to 1.3 +/- 0.6 U/mL at 12 months. These results indicate that GHRH administered by sc injection for a 1-yr period stimulated growth and GH secretion. However, a decrease in activity was noted during the last 3 months of treatment. Tests for anti-GHRH antibodies were positive in the only child who did not respond to treatment. PMID- 3110203 TI - Lack of bromocriptine-induced reduction of predicted height in tall adolescents. AB - Fifteen girls and five boys with excessive predicted adult height (chronological age, 10.1-14.6 yr; bone age, 11.0-14.0 yr) were treated with bromocriptine (two doses; 2.5 mg/day) to reduce their final height. After a mean treatment period of 1.14 yr (range, 0.6-1.75 yr) we did not find a reduction of predicted adult height [difference, -0.5 +/- 3.5 (+/- SD) cm according to Bayley and Pinneau's tables (P = NS) and +0.2 +/- 2.5 (+/- SD) cm according to the method of Tanner (P = NS)]. Mean peak plasma GH concentrations after TRH administration before and during bromocriptine were 51.5 +/- 49.4 and 58.5 +/- 50.7 mU/L, respectively. The wide range of the GH values may be explained by physiological variation in this age group. After ingestion of 2.5 mg bromocriptine a significant increase in plasma GH occurred within 3 h in six adolescents tested. Our results do not support the concept that bromocriptine may reduce predicted adult height in tall adolescents by decreased GH secretion or acceleration of skeletal maturation. PMID- 3110204 TI - Lower serum free thyroxine (T4) levels in painless thyroiditis compared with Graves' disease despite similar serum total T4 levels. AB - Serum total T4 (T4), total T3 (T3), free T4 (FT4), free T3 (FT3), and T4-binding globulin concentrations and T3 resin uptake values were measured in 17 women with thyrotoxicosis due to painless thyroiditis (PT) and compared with the same parameters in 17 women with thyrotoxicosis due to Graves' disease (GD) with similar serum T4 levels. The mean serum T3 resin uptake value and T3, FT4, and FT3 concentrations in the PT patients were significantly lower than those in the GD patients. The mean serum T4-binding globulin concentration [20.2 +/- 4.2 (+/- SD) microgram/mL] in patients with PT did not differ significantly from those in patients with GD (18.0 +/- 2.6 micrograms/mL) and normal euthyroid women (21.9 +/ 4.0 micrograms/mL). The serum T3 to T4 (nanogram per microgram) ratio was higher than 20 in 14 GD patients, but lower than 20 in all patients with PT, whereas the individual serum FT3 to FT4 ratio values considerably overlapped in the 2 groups. In patients with PT, FT4 correlated well with T4 at various times during the clinical course. These findings indicate that the elevation in serum FT4 in patients with PT is mostly due to the increase in circulating T4 levels, whereas GD patients also have some diminution in T4 binding. The serum T3 to T4 ratio, but not the FT3 to FT4 ratio, may be helpful for differentiation between the two diseases. PMID- 3110205 TI - Relative ability of modified versions of the hamster oocyte penetration test, incorporating hyperosmotic medium or the ionophore A23187, to predict IVF outcome. AB - This study was designed to assess the relationship between IVF outcome and the results obtained with two modified versions of the zona-free hamster oocyte penetration test in which the spermatozoa were pre-incubated with either hyperosmotic medium or the divalent cation ionophore A23187. When the former system was used, a poor correlation with IVF outcome was observed. Samples screened prior to IVF exhibited a 60% false negative rate (failed penetration test, successful IVF), while for those assessed concurrently with IVF, the equivalent figure was 85.7%. Addition of A23187 optimized the penetration system giving higher levels of sperm--oocyte fusion and a more accurate prediction of the capacity of the spermatozoa to fertilize human ova in vitro. With this system the false negative rate was 4.3% for screened samples and 0% for those assessed simultaneously with IVF. These results suggest that the A23187-enhanced system may be of value as a screening criterion for IVF. PMID- 3110206 TI - Candida parapsilosis fungemia associated with parenteral nutrition and contaminated blood pressure transducers. AB - During the period September 1983 through May 1985, Candida parapsilosis was isolated from intravascular sites (blood or vascular catheter tips) in 12 patients at a pediatric hospital. Of 205 patients with cultures of any site positive for Candida species, 32 (16%) had cultures positive for C. parapsilosis. In contrast, of 23 patients with intravascular cultures positive for Candida species, 12 (51%) had cultures positive for C. parapsilosis (P less than 0.001, Fisher's exact test). The 12 patients with intravascular cultures positive for C. parapsilosis were more likely to have received central venous nutrition therapy (10 of 12 versus 7 of 23; P less than 0.01, Mantel-Haenzel chi-square test) and had a longer duration of exposure to blood pressure transducers (P less than 0.08, paired t test) than the 23 ward- and age-matched controls. C. parapsilosis was isolated from 11 (32%) of 34 in-use and stored blood pressure transducers. After ethylene oxide sterilization of blood pressure transducers was begun, in use pressure transducers showed no growth of C. parapsilosis. This study emphasizes the role of C. parapsilosis as a nosocomial pathogen associated with invasive devices and parenteral nutrition; it also emphasizes the importance of adhering to recommended procedures for sterilizing blood pressure transducers. PMID- 3110207 TI - Interleukin 2 and gamma interferon production, interleukin 2 receptor expression, and DNA synthesis induced by tularemia antigen in vitro after natural infection or vaccination. AB - The T-cell response induced by Francisella tularensis antigen in sensitized subjects was characterized in vitro by measuring DNA synthesis in whole-blood and mononuclear cell cultures, interleukin 2 (IL-2) and gamma interferon (IFN-gamma) production, and IL-2 receptor expression. Correlations between these variables were estimated. The strengths of the responses were compared in 21 subjects naturally infected 2 years ago, 6 subjects vaccinated 5 to 6 years ago, and 13 control subjects with no history of infection or vaccination. Subjects with a history of natural infection synthesized more DNA in both whole-blood and mononuclear cell cultures, secreted more IL-2 and IFN-gamma, and expressed more IL-2 receptors than control subjects did. All these responses differed highly significantly (P less than 0.001) from those of the control subjects. The vaccinees exhibited somewhat lower responses than the naturally immunized subjects did, but the vaccinees could be distinguished from the control subjects by their DNA synthesis, receptor expression, and IFN-gamma production (P less than 0.01 to 0.001). The vaccinees showed a lower response, in terms of DNA synthesis and IL-2 secretion (P less than 0.05), than the infected group did but responded in a manner similar to that of this group, with respect to receptor positivity and IFN-gamma secretion (P greater than 0.10). The correlations between all the T-cell functions were good, with highly significant correlations (P less than 0.001) between whole-blood DNA synthesis and IL-2 and IFN-gamma secretion and between the two lymphokines (P less than 0.001). The results not only increase our knowledge of the T-cell response to tularemia antigen but also give an alternative approach to DNA synthesis measurement for the quantitation of T-cell responses. The results for the low-responding sensitized subjects seem to indicate that the parameters were comparable in sensitivity. PMID- 3110208 TI - MHC antigen expression on bulk isolated macrophage-microglia from newborn mouse brain: induction of Ia antigen expression by gamma-interferon. AB - Macrophage-microglia were isolated from primary mixed brain cell cultures of normal newborn mice. They were successfully maintained in vitro for at least 8 weeks. Purity of the cultures was 97-100%, as determined by endocytosis of latex beads, non-specific staining through Fc receptors, EA and EAC rosette formation. These cells were non-specific esterase-positive, but peroxidase-negative. Electron-microscope observations revealed morphological similarities to mature macrophages. Isolated macrophage-microglia seldom incorporated [3H]thymidine in vitro. By means of 51Cr release assay, using monoclonal antibodies against mouse major histocompatibility complex (MHC) antigens and complement, we detected class I MHC (H-2) antigen on unstimulated macrophage-microglia, and both class I and class II (Ia) antigens on gamma-interferon-treated cells. These observations suggest possible immunoregulatory functions of macrophage-microglia in the central nervous system, as is characteristic of other cells of monocyte lineage. PMID- 3110209 TI - Caffeine enhances the slow-pressor response to angiotensin II in rats. Evidence for a caffeine-angiotensin II interaction with the sympathetic nervous system. AB - The purpose of this study was to determine if caffeine augments the slow-pressor response to chronic low-dose infusions of angiotensin II (AII) or the rapid pressor response to acute infusions of AII. AII was infused (125 ng/min i.p.) for 12 d via mini-osmotic pumps in four groups of rats: group I, intact rats not treated with caffeine (n = 9); group II, intact rats treated with caffeine (0.1% in drinking water, n = 9); group III, rats previously sympathectomized with 6 hydroxydopamine, but not treated with caffeine (n = 10); and group IV, rats previously sympathectomized with 6-hydroxydopamine and treated with caffeine (n = 10). Chronic low-dose AII infusions slowly elevated systolic blood pressure in all groups. Caffeine greatly augmented this slow-pressor response to AII in intact animals; however, caffeine failed to enhance AII-induced hypertension in sympathectomized rats. Caffeine pretreatment did not enhance the rapid-pressor response to acute intravenous infusions of AII. We conclude that caffeine augmented the slow-pressor effect of chronic low-dose infusions of AII via a mechanism that involved the sympathetic nervous system. PMID- 3110210 TI - Blood flow measurements in autotransplanted pancreatic islets of the rat. Impairment of the blood perfusion of the graft during hyperglycemia. AB - No information is available on the rate of blood flow in transplanted islets. In this study, adult rats were partially depancreatized, and islets from the excised pancreas were then isolated, maintained for 7 d in tissue culture, and subsequently transplanted back to the animal, beneath the renal capsule. Some rats were rendered diabetic with streptozotocin before transplantation. A month after transplantation the blood flow of the grafts was measured by a microsphere technique. Autotransplantation to streptozotocin-diabetic rats of approximately 500 islets did not revert the hyperglycemia, and the blood flow of these grafts was approximately 25% of that in the normoglycemic-transplanted rats. However, in insulin-treated diabetic rats the blood flow of the pancreatic graft was similar to that in the normoglycemic rats. The present results suggest that the blood flow in transplanted islets is markedly diminished by hyperglycemia and that this can be enhanced by insulin administration. PMID- 3110211 TI - Stimulation of insulin secretion reveals heterogeneity of pancreatic B cells in vivo. AB - We examined the immunofluorescence and ultrastructural changes of insulin producing B cells in the center and at the periphery of islets of Langerhans during in vivo stimulation by glucose and glibenclamide. A decreased insulin immunostaining was detected in islets from the splenic rat pancreas after 1.5 h of glucose stimulation. By contrast, immunofluorescence changes became apparent in islets from the duodenal pancreas only after greater than 3 h of hyperglycemia. In both cases, the immunolabeling of central B cells decreased before that of peripheral B cells. Similar changes were seen following in vivo stimulation of insulin secretion by glibenclamide. At the ultrastructural level, hyperglycemia decreased the volume density of B cell secretory granules and increased that of rough endoplasmic reticulum and Golgi apparatus. These changes were also detected earlier in central than in peripheral B cells and earlier in splenic than in duodenal islets. The data show that B cells form a heterogeneous population in vivo. PMID- 3110212 TI - Glucuronidation of 6 alpha-hydroxy bile acids by human liver microsomes. AB - The glucuronidation of 6-hydroxylated bile acids by human liver microsomes has been studied in vitro; for comparison, several major bile acids lacking a 6 hydroxyl group were also investigated. Glucuronidation rates for 6 alpha hydroxylated bile acids were 10-20 times higher than those of substrates lacking a hydroxyl group in position 6. The highest rates measured were for hyodeoxy- and hyocholic acids, and kinetic analyses were carried out using these substrates. Rigorous product identification by high-field proton nuclear magnetic resonance and by electron impact mass spectrometry of methyl ester/peracetate derivatives revealed that 6-O-beta-D-glucuronides were the exclusive products formed in these enzymatic reactions. These results, together with literature data, indicate that 6 alpha-hydroxylation followed by 6-O-glucuronidation constitutes an alternative route of excretion of toxic hydrophobic bile acids. PMID- 3110213 TI - Synergism of platelet-aggregating agents. Role of elevation of cytoplasmic calcium. AB - When a pair of platelet agonists, each in subthreshold concentration, is added together or in sequence to a platelet suspension, the platelet response is enhanced. Addition of two agonists to platelets loaded with aequorin also enhanced the observed rise in cytoplasmic ionized calcium ([Ca2+]i) in response to the second agonist if the agonists were added within 20 s of each other. Enhancement of aggregation and secretion required that an increase in [Ca2+]i (as indicated by aequorin but not necessarily indo-1) followed the first agonist, but not that the [Ca2+]i remain elevated until addition of the second agonist. Enhancement was not prevented by aspirin, ADP scavengers, or chelators of extracellular Ca2+. We conclude that a rise in [Ca2+]i induced by a first agonist "primes" platelets for an augmented functional response to a second agonist, which is not, however, determined by the [Ca2+]i at the time of addition of the second agonist. PMID- 3110214 TI - Effects of chloride and extracellular fluid volume on bicarbonate reabsorption along the nephron in metabolic alkalosis in the rat. Reassessment of the classical hypothesis of the pathogenesis of metabolic alkalosis. AB - Volume expansion has been considered essential for the correction of chloride depletion metabolic alkalosis (CDA). To examine the predictions of this hypothesis, rats dialyzed against 0.15 M NaHCO3 to produce CDA and controls, CON, dialyzed against Ringer-HCO3 were infused with either 6% albumin (VE) or 80 mM non-sodium chloride salts (CC) added to 5% dextrose (DX) and studied by micropuncture. CDA was maintained in rats infused with DX. VE expanded plasma volume (25%), maintained glomerular filtration rate (GFR), but did not correct CDA despite increased fractional delivery of total CO2 (tCO2) out of the proximal tubule (36 +/- 2%) as compared with VE/CON (24 +/- 4%; P less than 0.05). In contrast, CC corrected CDA despite volume contraction (-16%) and lower GFR than CC/CON; proximal tCO2 delivery in CC/CDA (29 +/- 4%) did not differ from VE/CDA. CC was associated with an increment in tCO2 excretion. The data strongly suggest that maintenance and correction of CDA are primarily dependent upon total body chloride and its influences on intrarenal mechanisms and not on the demands of sodium or fluid homeostasis. PMID- 3110215 TI - Safety and immunogenicity of a Pseudomonas aeruginosa O-polysaccharide toxin A conjugate vaccine in humans. AB - Lipid A-free polysaccharide (PS) isolated from Pseudomonas aeruginosa immunotype 5 lipopolysaccharide (LPS) was covalently coupled to toxin A via reductive amination. The PS-toxin A conjugate was comprised of 29.8% PS and 70.2% toxin A, possessed a molecular weight of greater than 1 X 10(6), was nontoxic for animals and was nonpyrogenic for rabbits at a dose of 50 micrograms/kg body wt when administered intravenously. The conjugate evoked only mild, transient reactions upon subcutaneous administration to human volunteers. Vaccination engendered immunoglobulin G (IgG) antibody, which neutralized the cytotoxic effect of toxin A and promoted the uptake and killing of P. aeruginosa in the presence of human polymorphonuclear leukocytes. Passively transferred IgG isolated from the serum of immunized donors was far more effective at preventing fatal P. aeruginosa burn wound sepsis than paired preimmunization serum. These studies establish the potential usefulness of such a PS-toxin A conjugate as a vaccine against P. aeruginosa. PMID- 3110217 TI - Regulation of glycogen synthase and phosphorylase activities by glucose and insulin in human skeletal muscle. AB - We examined the insulin dose-response characteristics of human muscle glycogen synthase and phosphorylase activation. We also determined whether increasing the rate of glucose disposal by hyperglycemia at a fixed insulin concentration activates glycogen synthase. Physiological increments in plasma insulin but not glucose increased the fractional activity of glycogen synthase. The ED50: s for insulin stimulation of whole body and forearm glucose disposal were similar and unaffected by glycemia. Glycogen synthase activation was exponentially related to the insulin-mediated component of whole body and forearm glucose disposal at each glucose concentration. Neither insulin nor glucose changed glycogen phosphorylase activity. These results suggest that insulin but not the rate of glucose disposal per se regulates glycogen synthesis by a mechanism that involves dephosphorylation of glycogen synthase but not phosphorylase. This implies that the low glycogen synthase activities found in insulin-resistant states are a consequence of impaired insulin action rather than reduced glucose disposal. PMID- 3110218 TI - Long-term hospitalization of nonorganic failure-to-thrive infants. PMID- 3110216 TI - Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport. Fatal infantile lactic acidosis and hypermetabolism with skeletal-cardiac myopathy and encephalopathy. AB - A mitochondrial defect was investigated in an infant with fatal congenital lactic acidosis (3-14 mM), high lactate-to-pyruvate ratio, hypotonia, and cardiomyopathy. His sister had died with a similar disorder. Resting oxygen consumption was 150% of controls. Pathological findings included increased numbers of skeletal muscle mitochondria (many with proliferated, concentric cristae), cardiomegaly, fatty infiltration of the viscera, and spongy encephalopathy. Mitochondria from liver and muscle biopsies oxidized NADH-linked substrates at rates 20-50% of controls, whereas succinate oxidation by muscle mitochondria was increased. Mitochondrial NADH dehydrogenase activity (complex I, assayed as rotenone-sensitive NADH oxidase, NADH-duroquinone reductase, and NADH cytochrome c reductase) was 0-10% of controls, and NADH-ferricyanide reductase activity was 25-50% of controls in the mitochondria and in skin fibroblasts. Activities of other electron transport complexes and related enzymes were normal. Familial deficiency of a component of mitochondrial NADH dehydrogenase (complex I) proximal to the rotenone-sensitive site thus accounts for this disorder. PMID- 3110219 TI - Pharmacokinetics of lithium in the elderly. AB - The disposition and elimination of lithium was examined in nine female geriatric patients (aged 67 to 80 years) maintained on lithium carbonate as a once daily dose (300 to 600 mg) for the treatment of recurrent depression. Following the morning lithium dose (0.21 +/- 0.06 mmol/kg/day, mean +/- standard deviation), a peak steady state serum concentration of 0.83 +/- 0.25 mmol/liter was achieved at 2.2 +/- 1.2 hours. The mean distribution half-life (alpha-t1/2) was 2.7 +/- 1.2 hours, with distribution being complete at 10.6 +/- 3.0 hours. The mean terminal elimination half-life (beta-t1/2), the mean apparent oral clearance (Cl), and the mean apparent volume of distribution (Varea) were 26.9 +/- 5.5 hours, 15.6 +/- 4.0 ml/min, and 0.64 +/- 0.16 liter/kg, respectively. Compared to a younger adult cohort (35 +/- 10 years), the lithium Cl and Varea were significantly reduced and the alpha- but not beta-t1/2 prolonged in the elderly (p less than 0.05). Based on these pharmacokinetic differences, geriatric patients may require one-third to one-half less lithium than younger adults. The 12-hour standard serum lithium concentration remained a value of minimal intersubject variability when lithium was administered once daily. However, the therapeutic concentration range based on this 12-hour standard serum lithium concentration needs to be redefined for the prophylaxis of unipolar disorders in the elderly. PMID- 3110220 TI - Chlorpromazine and the lupus anticoagulant. PMID- 3110221 TI - The spinothalamic tract: an examination of the cells of origin of the dorsolateral and ventral spinothalamic pathways in cats. AB - The locations of spinothalamic neurons and the funicular trajectories of their axons were studied in cats by retrograde transport of horseradish peroxidase (HRP). Five animals were used as controls to determine the cervical and lumbar laminar distributions of neurons contributing to the spinothalamic tract. An additional eight animals were used to determine the funicular trajectories of the spinothalamic axons of lumbar neurons by utilizing a series of thoracic spinal cord lesions in conjunction with retrograde transport of HRP from the sensory thalamus. Three of these animals underwent midthoracic ventral quadrant lesions, four animals underwent midthoracic dorsolateral funiculus lesions, and one animal underwent total spinal cord transection sparing the dorsal columns. The locations of the cells containing the HRP reaction product were then determined after a 3- to 5-day survival time, and the patterns of labeled cell locations of the lesion groups were compared to the control group patterns. In the lesioned animals, the cervical spinothalamic cell locations were used as a control to confirm the uniformity of the injection sites, transport and tissue processing. The major finding of this study is that there exist two distinct components of the spinothalamic tract. The dorsolateral spinothalamic tract (DSTT) is made up of axons originating in contralateral spinal cord lamina I and has negligible contribution from the deeper spinal cord laminae. The axons of lamina I cells cross segmentally and ascend exclusively in the dorsolateral funiculus (DLF). The DSTT comprises approximately 25% of the total spinothalamic input from the lumbar enlargement. The ventral spinothalamic tract (VSTT) is made up of axons originating in spinal cord laminae IV-V and VII-X. Very few lamina I cells contribute axons to the VSTT. This crossed pathway ascends in the ventrolateral and ventromedial portions of the spinal cord. No cells contributing to the spinothalamic tract were identified in spinal cord segments caudal to a dorsal column sparing lesion, indicating that there are no spinothalamic tract axons traveling in the dorsal columns. These results expand the classical concept of information processing by the spinothalamic tract. The DSTT is made up of lamina I cell axons. All lamina I spinothalamic cells respond exclusively to noxious peripheral stimuli. Hence the DSTT is a major nociceptive-specific ascending spinal pathway, yet lies outside the confines normally assigned to the spinothalamic tract.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3110222 TI - Fat within the falx: MR demonstration of falcine bony metaplasia with marrow formation. AB - Falcine bony metaplasia frequently is incorrectly labeled "dense calcification" on brain CT and conventional radiography. Of 3,000 brain magnetic resonance (MR) scans reviewed, 12 demonstrated a central area of increased signal intensity on T1 and T2 weighted images with a smooth peripheral rim of diminished signal intensity within the region of the falx. The central area of increased signal intensity corresponded to fat in the medullary cavity and the peripheral area of low signal intensity corresponded to cortical bone. The CT scans, available in nine of 12 patients, were compared with the MR scans and revealed dense mineralization in the corresponding region of the falx. A postmortem specimen of densely "calcified" falx cerebri was examined that revealed cortical bone and a medullary cavity complete with bony trabeculae and marrow. The MR findings of falx ossification should not be confused with other entities of greater clinical significance. PMID- 3110223 TI - Using high tech tools to create microcomputer software. PMID- 3110224 TI - Get going! Get done! Introductions and conclusions for your class. PMID- 3110225 TI - The research responsibility: spreading the word. PMID- 3110226 TI - Staff development: your role in patient care. PMID- 3110227 TI - Community education program possible through multi-hospital cooperation. PMID- 3110228 TI - Use of adult education principles in medication instruction. PMID- 3110229 TI - Portfolio: an alternative for returning RNs. PMID- 3110230 TI - Purification and characterization of a cell wall proteinase from Streptococcus lactis NCDO 763. AB - A proteinase was purified from a cell wall extract of a culture of Streptococcus lactis NCDO 763 grown in skim milk. Being active at a low pH (at pH 4.8 on haemoglobin and pH 6.0-6.5 on casein) and completely inhibited by diisopropylfluorophosphate, it was considered to be a serine proteinase partly inhibited by EDTA; the mol. wt was approximately 80,000. PMID- 3110231 TI - Peptidases from two strains of Pseudomonas fluorescens: partial purification, properties and action on milk. AB - Pseudomonas fluorescens strains 240 and 32A expressed cell-associated peptidase activity which was shown by subcellular fractionation to be primarily intracellular. Two peptidases were partly purified from strain 32A. One specifically hydrolysed N-alpha-benzoyl-DL-arginine-4-nitroanilide and was termed endopeptidase and the other hydrolysed L-lysine- and L-leucine-4-nitroanilide and was termed aminopeptidase. The endopeptidase had very low activity on bovine serum albumin compared with that of trypsin and probably was not a proteinase. The endopeptidase had a mol. wt of 33,000 and a pH optimum of 8.0. The enzyme was stimulated by Ca2+ and Mg2+ and inhibited by Co2+, Mn2+, Hg2+, Zn2+ and leupeptin. Soya bean trypsin inhibitor and phenylmethane sulphonyl fluoride (PMSF) had no effect on its activity. The aminopeptidase had a mol. wt of 44,000 and a pH optimum of 8.0. It was inhibited by all the metal ions mentioned above and by PMSF. Little proteolysis was found when ultra high temperature (UHT) sterilized milk was treated with cell-free extract from strain 32A. It was concluded that the cell-associated peptidases from Pseudomonas strains normally present in raw milk may not contribute significantly to the deterioration of UHT sterilized milk. PMID- 3110232 TI - Assay of proteinases of psychrotrophic bacteria in milk using hide powder azure and a simple procedure for clarification of milk. AB - The clarification of milk by addition of solutions of Triton X-100 and EDTA after digestion of added Hide Powder Azure (HPA) was found to provide a simple method of determining the extracellular proteinase activity of Gram-negative psychrotrophic bacteria in pasteurized whole milk. The light absorbance of the clarified HPA digestion product was measured directly, after a brief incubation period, and was stable to storage of samples in diffuse daylight for at least 2 d. Proteinase produced by growth in refrigerated whole milk of as few as 2.5 X 10(6) cfu ml-1 of Pseudomonas fluorescens AR11 was detected. PMID- 3110233 TI - Enhancement of immune response in mice fed with Streptococcus thermophilus and Lactobacillus acidophilus. AB - Swiss mice, fed for 8 consecutive d with 50 micrograms/d of viable cultures of Lactobacillus acidophilus and Streptococcus thermophilus, showed significant variation in their immune system. In order to study this phenomenon assays for macrophage and lymphocyte function were carried out. Both lactic acid bacteria enhanced significantly the enzymatic and phagocytic activity of peritoneal macrophages as checked against the controls and also accelerated the phagocytic function of the reticuloendothelial system as revealed by the carbon clearance test. On the 2nd d (100 micrograms), L. acidophilus reached a peak of K = .271, which remained high. Streptococcus thermophilus was effective only on the 2nd d and then decreased. The lymphocytic activity studied by immunoglobulin secreting cells was assayed by Jerne's method of plaque-forming cells (PFC). This activity also was increased by the two microorganisms. Streptococcus thermophilus proved more effective than L. acidophilus. Lactobacillus acidophilus and S. thermophilus activated macrophages and lymphocytes and produced the same increase in the immune response of mice whether administered orally or intraperitoneally. PMID- 3110234 TI - Treatment of digital myxoid cysts with carbon dioxide laser vaporization. AB - Digital myxoid cysts represent a relatively uncommon cutaneous disorder which have often proven refractory to conservative management. We report a series of ten patients with this condition who were effectively treated with carbon dioxide (CO2) laser vaporization. There has been no recurrence of cysts during a follow up period ranging from 14 to 44 months. PMID- 3110235 TI - Jejunostomy: highlights of care. PMID- 3110236 TI - Short bowel syndrome in children and adults. PMID- 3110237 TI - Is there coronary vasoconstriction after intracoronary beta-adrenergic blockade in patients with coronary artery disease. AB - Vasomotility of normal and stenosed coronary arteries was studied at rest and during supine bicycle exercise in 10 patients with classical exercise-induced angina pectoris receiving 1 mg intracoronary propranolol before the exercise test (propranolol group). Normal and stenotic coronary lumen areas were determined from biplane coronary arteriograms using a computer-assisted system. Measurements were performed at rest, after 1 mg intracoronary propranolol, during supine exercise (89 W for 3.4 minutes) and 5 minutes after 1.6 mg sublingual nitroglycerin administered at the end of the exercise test. The results were compared with previously obtained data on the effect of dynamic exercise on coronary lumen area in 12 patients receiving no medication (control group) and in 6 patients receiving 0.1 mg intracoronary nitroglycerin before the exercise test (nitroglycerin group). In the control group, coronary stenosis area decreased during exercise to 71% of levels at rest (p less than 0.001) whereas normal coronary lumen area increased to 123% of control (p less than 0.01). In the propranolol group both normal (113%, p less than 0.05 versus rest) and stenotic coronary lumen area (122%, p less than 0.05 versus rest) increased during exercise. A similar increase in both normal and stenotic areas was observed during exercise after pretreatment with 0.1 mg intracoronary nitroglycerin (123%, p less than 0.01 and 114%, p = NS versus rest). Sublingual administration of 1.6 mg nitroglycerin at the end of exercise increased coronary stenosis area to 145% (p less than 0.01 versus rest) in the propranolol group and to 115% in the control group (p = NS versus rest). It is concluded that intracoronary administration of propranolol does not potentiate coronary vasoconstriction of the epicardial vessels at rest and during exercise. In contrast, intracoronary propranolol prevents exercise-induced stenosis narrowing either because of reduced myocardial oxygen demand with a lower coronary blood flow resulting in a smaller transstenotic pressure gradient and, thus, a smaller flow-induced fall in stenosis distending pressure; or because of "local" beta-receptor blockade with unopposed distal arteriolar alpha-receptor tone, resulting in a higher poststenotic pressure and, thus, in a greater stenosis distending pressure; or because of a local anesthetic effect of propranolol with a decrease in calcium influx to the coronary smooth musculature. PMID- 3110238 TI - Dynamic coronary stenosis behavior in classic angina pectoris: active process or passive response? PMID- 3110239 TI - Effect of nitroglycerin during hemodynamic estimation of valve orifice in patients with mitral stenosis. AB - In patients with mitral stenosis, valve orifice calculations using pulmonary capillary wedge pressure as a substitute for left atrial pressure may overestimate the severity of disease. Previous studies have shown that mitral valve area determined from transseptal left atrial pressure measurements exceeds that area derived from pulmonary wedge pressure measurements. This is probably due to pulmonary venoconstriction, which is reversed by nitroglycerin. Nitroglycerin, 0.4 mg, was administered sublingually to 20 patients with mitral valve disease during preoperative cardiac catheterization using the pulmonary capillary wedge pressure as the proximal hydraulic variable. At the time of a peak hypotensive effect, 3 to 5 minutes after nitroglycerin administration, the mean pulmonary capillary wedge pressure decreased from 23 +/- 2 (mean +/- SEM) to 19 +/- 2 mm Hg (p less than 0.005). The mean diastolic transmitral pressure gradient (12.6 +/- 1.2 mm Hg before and 11.5 +/- 1.0 mm Hg after nitroglycerin; p = NS) and cardiac output (4.0 +/- 0.3 to 4.1 +/- 0.3 liters/min; p = NS) did not change significantly. Nevertheless, the hemodynamic mitral orifice area, calculated using the Gorlin formula, increased from 0.8 +/- 0.1 to 1.1 +/- 0.2 cm2 (p less than 0.05). In 12 patients with isolated mitral stenosis, without regurgitation, the mitral valve orifice area after nitroglycerin was 0.4 +/- 0.2 cm2 larger than it was before drug administration (p less than 0.05). Administration of nitroglycerin during evaluation of mitral stenosis eliminates pulmonary venoconstriction, which raises the pulmonary capillary wedge pressure above the left atrial pressure in some patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110241 TI - Paroxysmal nonreentrant supraventricular tachycardia due to simultaneous fast and slow pathway conduction in dual atrioventricular node pathways. AB - Electrophysiologic studies were performed on a 49 year old woman who had paroxysmal nonreentrant supraventricular tachycardia due to simultaneous anterograde conduction through dual atrioventricular (AV) node pathways. Slow pathway conduction was inversely related to the preceding sinus cycle length and fast pathway conduction was determined by the Hs-A interval (measured from the His potential due to slow pathway conduction to the onset of the subsequent atrial electrogram). Major determinants of sustained simultaneous anterograde fast and slow pathway conduction during sinus rhythm were 1) a retrograde unidirectional block in both fast and slow pathways, and 2) a critical conduction delay in the slow pathway and a long enough Hs-A interval to allow sequential conduction of impulse from both pathways. Flecainide was successful in preventing recurrences of the tachycardia by eliminating slow pathway conduction during long term follow-up. PMID- 3110240 TI - Coexistent Mahaim and Kent accessory connections: diagnostic and therapeutic implications. AB - Six patients with coexistent Mahaim and Kent accessory connections are described. Two had left nodoventricular Mahaim connections, the first reported cases demonstrating these findings. In neither were the left-sided Mahaim connections components of a tachycardia and their presence was incidental. In two of four with nodoventricular connections, associated atrioventricular (AV) node conduction and coexistent posteroseptal accessory pathways were found. One of these had the unusual finding of a right-sided Mahaim connection arising from a "fast" AV node pathway. In only one patient did the tachycardia incorporate the Mahaim connection. In this patient, anterograde conduction during tachycardia occurred over a right nodoventricular connection whereas retrograde conduction occurred through a concealed right free wall Kent connection. Two patients had fasciculoventricular connections that were associated with either septal (one patient) or left free wall (one patient) Kent connections. The latter also had evidence of enhanced AV node conduction. This report is unique in that it describes in detail two patients with left nodoventricular connections (Mahaim) inserting in or near the left posterior fascicle. Combined Kent and Mahaim connections, present in the six patients, appear to occur in approximately 5% of patients with the Wolff-Parkinson-White syndrome. Precise identification of bypass connections critical for reentrant circuits is essential for intelligent application of treatment options. PMID- 3110242 TI - National health care and the elderly. PMID- 3110243 TI - Sociopolitical and ethical considerations in the treatment of cardiovascular disease in the elderly. PMID- 3110244 TI - Caloric requirements in total parenteral nutrition. AB - Resting energy expenditure (REE) was measured in 100 consecutive total parenteral nutrition (TPN) patients. Only forty-eight percent of the measured REEs were within 90-110% of the predicted Harris-Benedict values. A literature review revealed 191 published guidelines for non-protein caloric requirements of hospitalized TPN patients. These guidelines were appropriately matched and applied to the 100 individual TPN patients. The relationship between the recommended caloric supply and measured caloric expenditure was minimal. The recommendations exceeded measured REE by an average of 1076 +/- 660 kcal/day. These published guidelines were substantially above and below caloric requirements based on measured REE for both fat maintained (130% REE) and fat depleted (150% REE) patients. Following published guidelines rather than standards based on measured REE results in the administration of 6947 excess liters of TPN per year. Improvement in the precision of TPN caloric prescription can be accomplished by using measured REE as a reference base. When published guidelines were compared to prescriptions based on measured REE it was found that published guidelines were inaccurate both overall and individually and a substantial cost savings justifies actual measurement of energy needs. PMID- 3110245 TI - Disodium cromoglycate inhibits activation of human inflammatory cells in vitro. AB - Recent clinical studies indicate that disodium cromoglycate (DSCG) may have a direct effect on inflammatory cells because the drug reversed various changes in leukocyte function, such as increased membrane-receptor expression and enhanced cytotoxic capacity observed in peripheral white blood cells from subjects with asthma undergoing allergen-inhalation challenge. In the present study, we have demonstrated that DSCG, at low concentrations (a concentration of drug required to produce 50% inhibition, approximately 10(-8) mol/L) and in a time-dependent fashion, directly inhibited the activation in vitro of human neutrophils, eosinophils, and monocytes. Peripheral blood leukocytes were incubated with the synthetic chemoattractant, formyl-methionyl-leucyl-phenylalanine (at an optimal concentration of 10(-8) mol/L), and activation was assessed by measuring increases in the percentages of complement and IgG (Fc) rosettes as well as the enhanced capacity of these cells to kill target organisms (schistosomula of Schistosoma mansoni). DSCG at a concentration of 10(-7) mol/L totally inhibited both the formyl-methionyl-leucyl-phenylalanine-induced enhancement of complement and IgG rosettes, as well as increased schistosomular killing. These observations indicate that DSCG directly inhibits the secretory properties of inflammatory cells and that in turn might have important implications in modulating mechanisms contributing to the inflammatory component of asthma and allergic disease. It may also help to explain why compounds with considerably greater mast cell stabilizing properties than DSCG have been so disappointing when they are evaluated clinically. PMID- 3110246 TI - Acquired deficiency of the inhibitor of the first component of complement: report of five additional cases with commentary on the syndrome. PMID- 3110247 TI - Cromolyn sodium inhibits the increased responsiveness to methacholine that follows ultrasonically nebulized water challenge in patients with asthma. AB - We have previously reported that airway responsiveness to inhaled methacholine in subjects with asthma is increased 40 to 60 minutes after challenge with ultrasonically nebulized water. This study reveals that increased responsiveness to methacholine is abolished by administration of cromolyn sodium before the water challenge. The mean dose of methacholine (95% confidence limits) inducing a 20% fall in FEV1 (PD20) was 1.10 mumol (0.43 to 2.80). The PD20 after water challenge was 0.42 mumol (0.17 to 1.01) that was significantly lower (p less than 0.005) than that observed for the initial challenge. Administration of cromolyn before the water challenge abolished this increased responsiveness to methacholine. The mean PD20 was 1.32 mumol (0.47 to 3.68) that was not significantly different from that measured for the initial methacholine challenge. Methacholine responsiveness was unchanged when challenge was performed 40 to 60 minutes after cromolyn alone or after methacholine itself. We conclude that cromolyn abolishes the increased responsiveness to methacholine and probably does so by inhibiting the release of mediators. PMID- 3110248 TI - A comparison of the effects of sodium cromoglycate and beclomethasone dipropionate on pulmonary function and bronchial hyperreactivity in subjects with asthma. AB - After a run-in period of 2 weeks, receiving a regimen of inhaled beta 2-agonists and/or theophyllines, 38 atopic patients with asthma with perennial symptoms were randomly allocated to receive an 8-week treatment of additional inhalation treatment with either sodium cromoglycate (SCG), 2 mg four times daily, and placebo beclomethasone dipropionate (BDP), or BDP, 200 micrograms twice daily, and placebo SCG. After crossover, each group received the opposite treatment for the final 8 weeks. FEV1, FVC, and provocation concentration of histamine causing a 20% fall in FEV1 (PC20) were determined monthly and peak expiratory flow (PEF) daily throughout the study. A significant increase in FEV1, FVC, and PEF (p less than 0.01) was observed after BDP treatment was started, and likewise, in the second period, an increase in both FEV1 and PEF (p less than 0.05) was observed. The total effect on logarithm-natural (Ln) (PC20), i.e., the mean effects of the two periods, was also significant (p less than 0.01). SCG, however, was most effective when it was used as the first drug, indicated by a significant increase in FVC in the first period (p less than 0.05). Neither in the first nor in the second period did SCG treatment influence the Ln (PC20) value positively, and the SCG treatment administered in the second period could not maintain the improvement in the pulmonary function (i.e., FEV1, FVC, and PEF) obtained initially with the BDP treatment. When the effect of BDP on FEV1, FVC, PEF, and Ln (PC20) was compared to the effect of SCG in the first 8-week treatment period, no significant difference was observed (p greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110249 TI - Metabolic bone disease in home total parenteral nutrition. AB - Home total parenteral nutrition (HTPN) is in its infancy but has proved to be lifesaving for patients unable to manage on enteral nutrition alone. However, this mode of nutrition therapy is not without problems. Aside from mechanical and other metabolic complications, a peculiar metabolic bone disease has been reported to occur in some HTPN recipients. The disease, characterized by abnormalities in calcium and phosphorus homeostasis, often results in osteomalacia, bone pain, and fractures. Reports of approximately 50 cases of metabolic bone disease have been published by centers in the United States and Canada. Factors that have been implicated as possible causes include infusion of excess vitamin D, aluminum, calcium, protein, or glucose; cyclic vs. continuous TPN administration; and the patient's previous nutritional state. Although removal of vitamin D or aluminum from the TPN solution and discontinuation of TPN altogether have been associated with improvement in symptoms, histology, and laboratory values, no single factor has been identified as the cause of this troubling phenomenon. PMID- 3110250 TI - Luteinizing hormone pulsatile secretion and pituitary response to gonadotropin releasing hormone and to thyrotropin releasing hormone in male epileptic subjects on chronic phenobarbital treatment. AB - Endocrine changes have been reported in treated epileptic subjects, who often exhibit sexual dysfunctions, but the endocrine effects of single antiepileptic drugs have not been completely elucidated. In this study we have investigated the influence of phenobarbital (PB) on adenopituitary function and on peripheral sexual steroid pattern in 8 epileptic males. Chronic PB treatment does not modify luteinizing hormone (LH) pulsatile secretion. In the same subjects, LH and follicle stimulating hormone (FSH) response to Gonadotropin Releasing Hormone was blunted with respect to healthy controls both in terms of absolute values and of secretion areas. No difference was found in prolactin (PRL) response to Thyrotropin Releasing Hormone. In the epileptic group a significant increase in the levels of sex hormone binding globulin and a consequent decrease of the percent free testosterone have been observed. PB treatment also significantly lowers 17-beta-estradiol mean levels. These data suggest that PB independently affects both gonadotropin secretion and peripheral steroid pattern. PMID- 3110251 TI - A four generation study of familial dysalbuminemic hyperthyroxinemia: diagnosis in the presence of an acquired excess of thyroxine-binding globulin. AB - We have studied the largest kindred with familial dysalbuminemic hyperthyroxinemia (FDH) thus far reported, comprising thirty-three blood relations in four generations and three of their spouses. Our objective was to complement previous evidence concerning the precise mode of inheritance of FDH and to detect any other features of the disorder that had not yet been noted. Among the thirty three, there were thirteen patients with FDH, eight males and five females, in all of whom the abnormality appeared to be fully expressed. Within the kindred, no affected female has borne a female child, but transmission from female to male, male to male, and male to female has been observed. Among the offspring of individuals with FDH, the overall observed frequency of FDH in three filial generations was 12/22, or 54.5 per cent, yielding a computed penetrance ratio of 1.09. Four of the patients with FDH had been investigated for hyperthyroidism, and two of them had mistakenly been treated. Of particular interest were two women with FDH who were receiving oral contraceptives and whose serum thyroxine-binding globulin (TBG) concentrations were increased. The results of their thyroid function tests differed from those of patients with FDH whose TBG concentrations were normal and mainly suggested the presence of only a high TBG state. The diagnosis of FDH in these two patients was obscured, and probably would not have been made were it not for the present investigation, which led to the electrophoretic demonstration of increased binding of T4 by serum albumin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110252 TI - Pituitary function in human pseudocyesis. AB - Two young women with clinically established pseudocyesis were studied by endometrial biopsy, basal hormonal serum levels and dynamic pituitary testing. Basal serum levels of PRL and TSH were in the normal range; estradiol - 17 beta, progesterone and FSH were in the follicular phase range, but LH was in the follicular phase range in one patient and in the climateric range in the other one. The histologic assessment of the endometrial biopsies disclosed a proliferative endometrium in both patients. A group of six patients with hypothalamic amenorrhea were subjected to dynamic pituitary testing to compare results with those obtained in the two patients with pseudocyesis. The dynamic pituitary response to GnRH, TRH and metoclopramide was normal in the two patients with pseudocyesis and in the group with hypothalamic amenorrhea; moreover, challenge with estradiol benzoate (EB) in the two patients with pseudocyesis disclosed a normal positive feedback of LH. These observations and the analysis of data already published suggest that the amenorrhea of pseudocyesis is associated neither with a persistent corpus luteum nor chronic hyperprolactinemia. We suggest that an abnormality in neurotransmitter pathways results in alterations of pituitary hormone secretion. However, additional patients must be studied to prove or disprove this hypothesis. PMID- 3110253 TI - Increased level of thyroglobulin mRNA in a human familial goiter. AB - Thyroglobulin (Tg) and its specific mRNA were analyzed in the thyroid gland of two cases of familial goiter. A three-fold increase in the level of stable protein and functional Tg mRNA was found in the goiter of one of the two patients in whom a desiodase defect was demonstrated. Normal concentrations of both Tg and its mRNA were found in the other goiter in which no enzymatic defect could be shown. Our results suggest that the increase of Tg mRNA levels found in the goiter with a desiodase defect was due to a chronic stimulation of the gland by TSH. PMID- 3110254 TI - Ethanol influence on calcium uptake and insulin release by rat islets. AB - Effect of acute ethanol treatment on simultaneous 45Ca++ uptake and insulin response to glucose was measured in isolated rat pancreatic islets. Ethanol, given ip 1 gm/Kg 1 h prior to sacrifice of the animal, decreased significantly 45Ca++ uptake and insulin response to 8.3 and 16.7 mM glucose. Addition of ethanol to the incubation media inhibited 45Ca++ uptake and insulin release in a dose-related matter. Ionophore A23187, which is known to enhance 45Ca++ efflux, decreased 45Ca++ uptake without affecting insulin release. Inhibitory effects of ethanol and ionophore A23187 were not additive when islets were exposed to both test substances simultaneously. Forskolin, an activator of the adenylate cyclase system potentiated the glucose mediated insulin response in rat islets. However, ethanol decreased the insulin response of islets exposed to glucose and forskolin. The data show that ethanol inhibits 45Ca++ uptake response to glucose and that ethanol influence on insulin release may involve a site beyond the formation of cyclic AMP in the process of excitation-secretion coupling. PMID- 3110256 TI - Long term: insurance considerations. PMID- 3110255 TI - Hypothalamic secretion of thyrotropin releasing hormone declines in aging rats. AB - Young and aged male rats were used in experiments to investigate a possible decline in hypothalamic secretion of thyrotropin releasing hormone (TRH) to the anterior pituitary of aging mammals. We observed a 66% decrease in basal TRH release by incubated rat hypothalami with aging. Thyroid hormone-responsive hepatic alpha-glycerophosphate dehydrogenase (GPD) and malic enzyme (ME) levels in aged rats did not differ from 5-month-old controls in spite of a significant fall in serum thyroxine (T4) levels with aging. Other results suggest that these particular indicators of thyroidal status should not change in the aging rat because serum T3 is maintained in the normal range. Serum thyrotropin (TSH) levels, which normally rise when serum T4 levels decline, did not change with aging. These data suggest that gradual loss of the essential TRH stimulation of TSH release with aging may be compensated for by a decline in T4 inhibition of TSH release at the pituitary. PMID- 3110257 TI - [Ovarian function under mini-dose oral contraception. Echographic morphology of the ovaries and hormonology]. AB - The present study correlates ultrasound observations of ovaries with gonadotrophin and ovarian steroid levels in plasma in 18 women using oral contraception through 28 cycles. Follicles could often be made out with ultrasound. They were associated with measurable gonadotrophin values, but the resulting ovarian steroid production often seemed to be very low. However, there are exceptions as shown in one case described here in which ultrasound, gonadotrophin and oestrogen levels together show up coherently. Yet no ovulation was demonstrated. This preliminary study should encourage investigators to carry out further series. PMID- 3110258 TI - [Parenteral nutrition for Crohn disease in the third trimester of pregnancy. Apropos of a case]. AB - The authors report a case of Crohn's disease in pregnancy where complications made it necessary to give the digestive system a complete rest by using parenteral nutrition. A review of the literature shows that it is possible to use this technique in pregnancy. PMID- 3110259 TI - Valproate sodium in postanoxic choreoathetosis. PMID- 3110260 TI - Manic-depressive illness in children: treatment with lithium carbonate. AB - A behavior questionnaire was used retrospectively in 21 manic-depressive children to quantitate manic-depressive behaviors before and after treatment with lithium carbonate. The study children were matched with 21 control children for age, race, sex, and socioeconomic status. The study children had significantly more seizures, relatives with psychotic disorders, allergies, food sensitivities, headaches, and abnormal behaviors in all categories measured. During treatment, manic-depressive children had a statistically significant reduction in disturbed behavior. This behavior, however, was still significantly more disturbed than normal control children. PMID- 3110261 TI - Reflex epilepsy. PMID- 3110262 TI - The inherited neurodegenerative disorders of childhood: clinical assessment. AB - This review represents an examination of four groups of neurodegenerative diseases, namely the sphingolipidoses, the adrenoleukodystrophy complex, the neuronal ceroid lipofuscinoses, and the sialidoses/sialuria complex. Using a combination of clinical assessment, neuroradiologic appearance, and clinical neurophysiology, one may develop strategies that lead to specific chemical or biochemical determinations for specific diagnoses. In general, disorders of white matter may be distinguished from disorders of gray matter by their appearance on computed tomography and by abnormalities of nerve conduction velocities and auditory brain stem responses. In contrast, disorders of gray matter may be distinguished from disorders of white matter by their appearance on computed tomography and utilization of electroretinography, visual evoked responses, and, to a lesser extent, EEG findings. Where necessary, skin, conjunctival, or nerve biopsy may prove to be useful adjuncts to the diagnosis. Presently, treatment depends on prevention, although aggressive efforts are under way to establish corrective therapy by enzyme replacement. To this end, the use of already existing animal models may prove to be helpful. PMID- 3110263 TI - In vitro effects of lymphoblastoid interferon on lymphocyte activation and cell mediated cytolysis in patients with chronic hepatitis B virus infection. AB - In addition to a direct anti-viral effect, interferons have important immunological properties including effects on cell-mediated immunity and antibody production as well as cell-mediated cytolysis. In chronic hepatitis B virus infection the host immune system is important for the elimination of replicating virus and in addition to directly inhibiting hepatitis B virus replication, interferons may affect host immune responses. We investigated the effect of lymphoblastoid interferon in vitro on lymphocyte activation and cell-mediated cytolysis in patients with chronic hepatitis B virus infection. The proliferative response to the mitogen PHA was significantly impaired in patients compared to controls. In addition supernatants of cultured mononuclear cells from patients stimulated with PHA contained less interleukin-2 activity than controls while the proportion of stimulated mononuclear cells expressing the interleukin-2 receptor was also reduced in patients. Prior incubation with 10(3) U ml-1 lymphoblastoid interferon increased both interleukin-2 activity and interleukin-2 receptor expression in patients and controls, although in patients the response was less marked. In contrast the proliferative response was unaffected. Natural killer cell activity against K562 cells was similar in patients and controls which in both groups was significantly augmented by prior incubation with 10(3) U ml-1 lymphoblastoid interferon; the increase was inversely proportional to baseline activity. In contrast incubation of target or effector cells with interferon did not augment T-cell cytotoxicity against autologous hepatocytes. The effects of lymphoblastoid interferon in vitro, were modest, but subtle changes in immunological status in addition to a direct effect on viral replication may be relevant to eventual clearance of the hepatitis B virus. PMID- 3110264 TI - Fluvoxamine and imipramine: results of a long-term controlled trial. AB - Following a multicentre double-blind controlled trial comparing the effects of fluvoxamine and imipramine in depressed inpatients (M.D.E.) 39 patients continued on longer term treatment with maintenance of double-blind conditions (17 on fluvoxamine, 22 on imipramine). The results regarding the reasons for premature interruption of treatment show a slight advantage in favour of fluvoxamine. There were several significant differences in favour of fluvoxamine at the 20th week. The most common side-effects were hot flushes with imipramine and dizziness with fluvoxamine. Overall, despite the small number of patients, the results show a greater clinical tolerance to fluvoxamine than to imipramine. PMID- 3110265 TI - Autoradiographic demonstration of in vivo sialylation of endogenous acceptors at the microvillar surface of intestinal columnar cells after intraluminal administration of CMP-[3H]-sialic acid. AB - To investigate the presence of glycosyltransferase activity at the apical surfaces of columnar cells in small intestine, CMP-[3H]-sialic acid was injected into the lumen of a ligated segment of rat jejunum; 5 min later the tissue was fixed and processed for light microscopic autoradiography. After a 3-6-month exposure, an autoradiographic reaction appeared over the microvillar surfaces of columnar cells, indicating the presence of surface sialyltransferase activity accompanied by endogenous acceptors. When CMP-[3H]-sialic acid was injected into the posterior chamber of rat eye or the lumen of mouse gallbladder, no autoradiographic reaction was observed at the surfaces of the cells facing these cavities. After injection of UDP-[3H]-galactose into the same three sites, an autoradiographic reaction was observed in the Golgi regions of the various epithelial cells, but not along their apical surfaces. Competition experiments using unlabeled galactose indicated that [3H]-galactose had been released from the nucleotide and had entered the cells to be incorporated into the Golgi apparatus. PMID- 3110266 TI - Immunocytochemical localization of carbonic anhydrase in myelinated fibers in peripheral nerves of rat and mouse. AB - Rat sciatic nerve, spinal root, and cranial nerve were immunostained with an antibody against rat brain carbonic anhydrase II (ca), to determine the localization of ca in the rat peripheral nervous system (PNS). Similar methods were applied to mouse nerves to see if that antigen could be detected in the PNS of this species. In rat nerves, intense immunostaining was observed in the axoplasm of many of the myelinated fibers, whereas others were stained less intensely or were negative. A heterogeneous pattern of immunostaining was also found in neuronal perikarya within the ganglia, and in some regions of the ganglia ca immunostaining was found in putative satellite cells and their processes. Ca in rat PNS therefore appears to occur at both neuronal and glial sites, whereas it is exclusively glial in the CNS. In longitudinal sections of some fibers within rat nerves, ca immunostaining could be detected at the inner boundaries of the myelin sheaths. In mouse nerves, axoplasmic staining was observed but it was fainter than in rat nerves. Interspecies differences were most obvious in the dorsal columns of the spinal cord. In rat, intensely stained axons proceeded through the roots into the gracilis or cuneate and often into the gray matter. In mouse, there was much less immunostaining of axons but more intense ca immunostaining in CNS myelin than in the CNS myelin in the rat cord. The implications concerning putative functions of ca in the rodent nervous system are discussed. PMID- 3110267 TI - Population kinetics of precursors of IL 2-producing peripheral T lymphocytes: evidence for short life expectancy, continuous renewal, and post-thymic expansion. AB - The fate of spleen T cell populations able to produce IL 2 after stimulation with Con A (IL 2p) was evaluated at different times after injection into IL 2p deficient, syngeneic nude recipients. Precise enumeration of transferred cell populations in recipient organs was performed by limiting dilution analysis. The results obtained confirm previous findings on the short life-span of IL 2p cells. They also demonstrate that: the transferred populations containing IL 2p were capable of continuous renewal and expansion in the host; IL 2p cell expansion, a transient event that takes place predominantly in lymph nodes, is much reduced when injected cells are depleted of recent thymus migrants; in steady-state conditions, IL 2p T cells do not lose their self-renewal ability and maintain population sizes by continuous cell production and death in peripheral pools. The self-renewal capacity, the expansion potential of peripheral IL 2p T cells and, in particular, of recent thymus migrants may allow extensive post-thymic modulation of peripheral T cell specificities, suggesting that post-thymic selection may have a major role in the establishment of the available and actual mature IL 2p T cell repertoire. PMID- 3110268 TI - Dissociation between the expression of IL 2 receptor and IL 2 receptor mRNA in the antigen-specific T cell clone stimulated by the specific antigen with B cell APC. AB - An antigen-presenting capacity of B cells was analyzed in comparison with that of whole spleen cells in terms of IL 2R expression of a human IgG-specific T cell clone, 24-2C.3. When the clone was stimulated with the antigen and irradiated spleen cells, the clone expressed an adequate amount of IL 2R on the surface in flow cytometric analysis. On the other hand, the clone expressed the receptor only poorly, being stimulated with B cell APC. The findings were confirmed by Western blot analysis on the clone solubilized by Nonidet P-40 and also by fluorescent antibody technique on the fixed clone. 24-2C.3 clone stimulated with B cell APC was also suggested not to secrete IL 2R in culture medium. In dot blot hybridization analysis performed with cDNA probe, however, 24-2C.3 clone stimulated with B cell APC was shown to express a comparable amount of IL 2R mRNA to the clone stimulated with whole spleen cells as APC. The mRNA expressed in the clones stimulated with B cells and with spleen cells could not be distinguished from each other in Northern blot analysis. The culture supernatant of 24-2C.3 clone incubated with the antigen and irradiated spleen cells was shown to enhance the expression of IL 2R on the clone stimulated with B cell APC. These results suggest that there is some defect in the antigen-presentation capacity of B cells in terms of the elicitation of the intracellular signal for IL 2R expression in T cells and that the humoral factor(s) produced in the presence of splenic adherent cells could supply the defect. PMID- 3110269 TI - Differential effects of antibodies to Lyt-2 and L3T4 on cytolysis by cloned, Ia restricted T cells expressing both proteins. AB - Cloned T cell lines specific for the antigen ovalbumin (OVA) in the context of self I-A or I-E class II MHC-encoded molecules were found to express equivalent levels of the Lyt-2 and L3T4 surface molecules by FACS analysis. Functionally, these cloned T cell lines will kill OVA-pulsed, class II MHC-bearing B lymphoma cells. This system allowed us to examine the relative contribution of the Lyt-2 and L3T4 molecules to recognition of antigen in the context of self class II MHC molecules. We find that anti-L3T4 is 25- to 100-fold more potent at inhibiting cytotoxicity by these cloned lines than is anti-Lyt-2, where potency is calculated as the ratio of the concentration needed for inhibition divided by the concentration needed for binding. Both antibodies can completely inhibit cytotoxicity. These results suggest that the accessory molecules Lyt-2 and L3T4 can play two different roles in antigen:MHC recognition. In class II MHC recognition, L3T4 plays a dominant role, highly sensitive to inhibition by anti L3T4. By contrast, Lyt-2 plays a minor yet important role in the cell interaction, perhaps by adhesion strengthening. Previous analysis in several laboratories supports the concept that the ligand for L3T4 is class II MHC, whereas the ligand for Lyt-2 is class I MHC. The present results are consistent with the hypothesis that these molecules are actually part of the T cell antigen:MHC recognition complex, and play an important role in the class of MHC molecule recognized by a T cell alpha:beta heterodimeric receptor. As such, they are not accessory proteins, but a direct part of the recognition apparatus, and the term accessory protein may apply only in those cases in which the specificity of the T cell receptor is for a different class of MHC than that normally associated with the L3T4 or Lyt-2 molecule. PMID- 3110270 TI - Immunity to D-penicillamine: genetic, cellular, and chemical requirements for induction of popliteal lymph node enlargement in the mouse. AB - To elucidate the pathogenesis of immunological diseases induced by the drug D Penicillamine (D-Pen) the requirements for sensitization to this drug were investigated. Mice were subcutaneously (s.c.) injected into one hind footpad with a solution of D-Pen without adjuvant, and reactivity to D-Pen was determined in the popliteal lymph node assay (PLNA) by weight increase of the draining PLN, the incorporation of 3H-thymidine, and trapping of 51Cr-labeled syngeneic lymphocytes in the draining PLN. The peak of the primary PLN response was obtained between day 7 and 10 after injecting 1 mg of D-Pen per mouse. Likewise, PLN enlargement could be induced by injecting 18 hr nonadherent spleen cells s.c. that had been pretreated overnight with D-Pen in vitro. D-Pen-induced PLN enlargement was primarily caused by cell proliferation within the lymph node, and only a minor portion was due to trapping of circulating lymphocytes. The majority of the cells in the enlarged PLN were B cells; T cells, however, were required for generation of PLN enlargement. For induction of PLN reactivity to D-Pen, the stereoisomer L Pen, and the dimer D-Pen disulfide, it was mandatory that the respective molecules were administered in ionized form. PLN reactivity to D-Pen is controlled by at least two loci, one mapping to the I region, possibly A beta A alpha, the other(s) to the non-H-2 background. As far as studied, high responsiveness was inherited dominantly. The PLN reaction proved to be antigen specific, since D-Pen-primed mice exhibited an enhanced reaction when challenged with a suboptimal dose of D-Pen, but not when challenged with an unrelated drug, diphenylhydantoin (DPH). The possible relationship between immunity to D-Pen and autoimmunity induced by this drug is discussed. PMID- 3110271 TI - rIL 2-induced proliferation of human circulating NK cells and T lymphocytes: synergistic effects of IL 1 and IL 2. AB - Cells participating in the rIL 2-induced proliferation of resting PBMC were identified by using different methods of cell purification. NK cells recovered in the light density fraction of Percoll gradients responded, as already known, directly to rIL 2 by strong proliferation. In contrast, large T lymphocytes co purifying with NK cells, and small T cells sedimenting in the high density area of the Percoll gradients, were virtually unresponsive when cultivated in the sole presence of rIL 2. However, the addition of either irradiated autologous monocytes or highly purified IL 1 allowed both kinds of T cells to undergo cell division. Stringent elimination of possibly contaminating NK cells (NKH-1+) and/or activated T cells (TNKTAR, Tac+, HLA-DR+) from the high density T cells by complement lysis did not impair rIL 2-induced cell proliferation, indicating entire responsiveness of these cells to the synergistic action of IL 1 plus IL 2. Both high density CD4+ and CD8+ participated in this phenomenon, with an apparent advantage for CD4+ cells. All Tac+ cells emerging in a 6-day culture of these cells expressed the WT31 antigen, which indicates that T cells involved in rIL 2 induced proliferation are conventional mature T cells. The relative precursor frequencies of NK cells, large T lymphocytes, and small T lymphocytes that proliferated in response to rIL 2 were analyzed by limiting dilution analysis. The frequencies of clonal growth of NK cells and low density T lymphocytes were approximately the same (1/103 vs 1/185), whereas that of high density T cells was four times lower (1/458). Thus, we clearly demonstrate that resting T cells, defined as such by morphological, density, and phenotypic criteria, are able to proliferate in response to IL 2 in the presence of IL 1 without antigenic or mitogenic triggering. PMID- 3110272 TI - Receptor-specific modulation of myelopoiesis by recombinant DNA-derived interleukin 2. AB - T cells and T cell-derived lymphokines have been implicated in the regulation of myelopoiesis. This study examines the regulatory effects of recombinant DNA derived human IL 2 on the phagocyte progenitor cell (CFU-GM), utilizing a receptor-specific model for T cell regulation of myelopoiesis. IL 2 receptors were induced on immunopurified marrow T cells by triggering the T cell antigen receptor complex with CD3 monoclonal antibody. IL 2 receptor expression was assessed by cytofluorography with IL 2 receptor monoclonal antibody. IL 2 receptor-positive and IL 2 receptor-negative marrow T cells were cocultured with autologous adherent and T cell-depleted marrow mononuclear cells in the absence and presence of various concentrations of IL 2. In the presence of IL 2 receptor positive T cells, IL 2 caused a dose-dependent inhibition of CFU-GM (86% at 10(2) U/ml). IL 2 did not inhibit CFU-GM in the absence of T cells or in the presence of IL 2 receptor-negative T cells. The addition of IL 2 receptor blocking monoclonal antibody completely abrogated IL 2-induced inhibition of CFU-GM. Conditioned media prepared from IL 2 receptor-positive marrow T cells in the presence of IL 2 also inhibited CFU-GM expression from marrow NAB-T cells (50% +/ 16). In contrast, conditioned media from IL 2 receptor-positive T cells prepared in the absence of IL 2 or from IL 2 receptor-negative T cells prepared in the presence or absence of IL 2 did not significantly affect CFU-GM growth. IL 2 receptor-positive, but not IL 2 receptor-negative, T cells released large amounts (190 +/- 60 U/10(6) cells X ml-1) of IFN-gamma but only low amounts of tumor necrosis factor beta (less than 10 U/ml) in response to IL 2. In control experiments, recombinant DNA-derived IFN-gamma caused a 37% +/- 19 inhibition of CFU-GM in the presence of resting T cells and adherent cells. However, IFN-gamma failed to inhibit CFU-GM in the presence of activated (IL 2 receptor-positive) T cells, indicating that release of IFN-gamma cannot solely explain IL 2-induced inhibition of CFU-GM. The addition of neutralizing IFN-gamma monoclonal antibody partially abrogated IL 2-induced inhibition of CFU-GM (41 to 60%) in the presence of CD3-triggered T cells, suggesting that although IFN-gamma participates in IL 2 induced inhibition of myelopoiesis, it is not the sole mediator of that inhibition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3110273 TI - Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines, or interferon-gamma. AB - Macrophage synthesis of nitrite and nitrate after activation by BCG infection or by treatment in vitro with both T cell-derived (lymphokines (LK) or recombinant murine interferon-gamma (IFN-gamma] and bacterial (lipopolysaccharide (LPS) and heat-killed bacillus Calmette-Guerin (hk BCG] agents was studied by using macrophages from C3H/He and C3H/HeJ mice. Spleen and peritoneal macrophages isolated from BCG-infected donors that were producing nitrate continued to synthesize nitrite and nitrate in culture. LPS treatment in vitro (25 or 50 micrograms/ml) additionally increased this nitrite/nitrate synthesis. Thioglycolate-elicited macrophages from non-infected C3H/HeJ mice treated with LK also produced nitrite/nitrate, and concurrent LPS (0.1 to 50 micrograms/ml) treatment resulted in enhanced synthesis. Recombinant IFN-gamma also stimulated nitrite/nitrate synthesis by C3H/He and CeH/HeJ macrophages as did LPS (C3H/He only) and hk BCG. When given concurrently with either LPS or hk BCG, IFN-gamma enhanced C3H/He and C3H/HeJ macrophage nitrite/nitrate synthesis over that produced by macrophages treated with either LPS or hk BCG alone. Macrophages activated in vitro exhibited a 4 to 12 hr lag time before engaging in nitrite/nitrate synthesis, which then proceeded for 36 to 42 hr at linear rates. Daily medium renewal did not alter the synthesis kinetics but increased the total amount of nitrite/nitrate produced. Nitrate and nitrite were stable under the conditions of culture and when added did not influence additional macrophage synthesis. Taken together, these results indicate that T cell lymphokines and IFN gamma are powerful modulators of macrophage nitrite/nitrate synthesis during BCG infection and in vitro, and nitrite/nitrate synthesis appears to be common property of both primed and fully activated macrophage populations. PMID- 3110274 TI - Molecular analysis of heavy and light chains used by primary and secondary anti (T,G)-A--L antibodies produced by normal and xid mice. AB - The primary (1 degree) antibody response to (T,G)-A--L shows limited heterogeneity, consisting mostly of side chain-specific antibodies that bind GT and that express the TGB5 idiotype (Id). The secondary (2 degrees) response is very diverse: antibodies that bind the backbone A--L constitute a third of the response, and a high proportion of the side chain-specific antibodies do not bind GT and are TGB5 Id-. To provide a molecular basis for understanding this difference in repertoire expression, we analyzed the Ig genes used by heavy and light chains of 1 degree and 2 degrees side chain-specific anti-(T,G)-A--L hybridoma antibodies (HP). Southern blot restriction analysis and nucleotide sequence analysis of the expressed genes used by three TGB5 Id+ 2 degrees HP showed usage of three different VH genes in two VH gene families (36-60 and J558), different D segments, and two different Vk1 genes (the Vk1A and Vk1C subgroups). Thus, antibody heterogeneity in the 2 degrees response is contributed by combinatorial diversity of distinct germ-line genes. Nucleotide sequence analysis of the expressed genes used by TGB5 Id+ 1 degree HP showed use of highly homologous VH genes in the J558 VH gene family and highly homologous Vk1A genes. The majority of TGB5 Id+ 1 degree HP from different donors gave similar heavy and similar light chain gene rearrangements by Southern blot restriction analysis, after correction for known or potential J region differences. The combined nucleotide sequence and Southern blot restriction analysis data suggest that most 1 degree B cells use the same or very similar VH and Vk genes, i.e., the 1 degree response is paucigenic. Different D segments were used by the TGB5 Id+ 1 degree and 2 degrees HP that were sequenced, and there was no apparent correlation between TGB5 idiotypy and VH, D gene, or JH gene usage. However, all TGB5 Id+ HP sequenced used highly homologous genes from the Vk1 group. Expression of a Vk1 light chain correlates with, but is not sufficient for, TGB5 idiotypy, because one GT-binding, TGB5 Id- HP was found to use a Vk1C subgroup light chain. By Southern blot and nucleotide sequence analysis, the Vk genes used by two TGB5 Id+ 2 degrees HP from xid mice are highly homologous, if not identical to the Vk1A gene(s) used by 1 degree and 2 degrees Id+ HP from wild-type mice. PMID- 3110275 TI - Absence of somatic mutation in the variable region of MPC 11 variants expressing a different heavy chain isotype. AB - Somatic mutation of immunoglobulin variable regions contributes to the diversity of the immune response. Some investigators have postulated that somatic mutation is coupled to isotype switching; others have presented evidence that the two processes are not linked. By using in vitro variants of the MPC 11 mouse myeloma cell line that produce heavy chains of different isotypes, we have examined several VH regions at the nucleotide level using a variety of different sequencing procedures. We have found no evidence of somatic mutation and conclude that the processes of somatic mutation and isotype switching may be independent. PMID- 3110276 TI - Structure-function analysis of the Abm12 beta mutation using site-directed mutagenesis and DNA-mediated gene transfer. AB - The B6.C-H-2bm12 (bm12) mouse possesses a naturally occurring mutation in its class II MHC A beta gene. The three amino acid substitutions at positions 67, 70, and 71 that comprise this mutation lead to changes in both Ia expression and immune recognition of the resultant A beta A alpha molecule. The experiments reported here utilize a combination of oligonucleotide-mediated site-directed mutagenesis and DNA-mediated gene transfer to explore the roles played by each of the three mutant residues in these various phenotypic changes. A beta genes comprising all permutations of the residues distinguishing Ab beta from Abm12 beta were created and were individually co-transfected with Ab beta into mouse L cells. Sublines expressing high levels of membrane Ia were selected by preparative flow cytometry and were studied for reactivity with a panel of monoclonal anti-Ia antibodies, or for their ability to act as antigen-presenting cells (APC) for the stimulation of T cell hybridomas. During the generation of these transfectant lines, it was noted that expression of a high level of Abm12 beta Ab alpha was more difficult to achieve than a similar level of Ab beta Ab alpha. Northern blot analysis of specific A beta and A alpha mRNA levels in these various lines indicated that more class II mRNA, and presumably more A beta and A alpha chains, were required to achieve expression of Abm12 beta Ab alpha equal to that of Ab beta Ab alpha, suggesting that the previously noted reduction of Ia expression on cells from bm12 mice reflects a decreased ability of Abm12 beta Ab alpha chains to pair, or to reach the membrane. Staining of the panel of transfectants with monoclonal antibodies revealed that antibodies which did not distinguish Ab beta Ab alpha from Abm12 beta Ab alpha also reacted equally well with all molecules involving in vitro mutant A beta chains. Monoclonal antibodies reactive with Ab beta Ab alpha but not Abm12 beta Ab alpha were specific for an epitope primarily determined by the presence or absence of Arg 70 in Ab beta. In striking contrast, all three mutant positions were found to play crucial roles in T cell recognition, because all substitutions led to significant or complete loss of antigen-presenting function with all but one of the T hybridomas tested.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3110277 TI - Induction of cytotoxicity in human peripheral blood mononuclear cells by monoclonal antibody OKT3. AB - It has been previously reported from this laboratory that incubation of PBMC with OKT3 generates potent cytotoxic lymphocytes that can be targeted by using antibody heteroconjugates consisting of anti-target cell antibody and OKT3. In the present study these conjugates were used to explore the kinetics of induction of cytotoxicity in PBMC and the subpopulations of lymphocytes involved. It was found that in addition to conjugate-dependent cytotoxicity, a considerable amount of conjugate-independent cytotoxicity was generated during OKT3 stimulation. Although the conjugate-dependent activity resided in the CD8+ population, the conjugate-independent cytotoxicity was found to be a function of CD4-/CD8- natural killer-like cells. Being largely CD3-, those cells were most likely activated by lymphokines produced by OKT3-stimulated CD3+ cells. They were capable of killing not only tumor cells but also autologous lymphocytes. The CD4+ cells of some donors were found to exhibit low but clearly demonstrable cytotoxicity. Induction of cytotoxicity was characterized as an early event in T cell activation, correlating with the kinetics of RNA synthesis. Cytotoxicity, interleukin 2 receptor expression, and DNA synthesis declined after 3 days of activation with OKT3, indicating the existence of as yet undefined regulatory mechanisms. PMID- 3110278 TI - Cross-linking of T3 (CD3) with T4 (CD4) enhances the proliferation of resting T lymphocytes. AB - Monoclonal antibodies reactive with defined T lymphocyte surface antigens were covalently coupled to protein A-Sepharose beads using the bifunctional imidoester, dimethyl pimelimidate. Sepharose-immobilized antibody reactive with T3 induced the proliferation of resting T lymphocytes in the presence of either recombinant interleukin 2 or phorbol myristate acetate. When monoclonal antibodies reactive with T3 and T4 were coupled to the same Sepharose bead (hereafter designated Sepharose (T3:T4)), proliferation was enhanced an average of three-fold. Similarly prepared Sepharose beads coupled to anti-T3 and anti-T8 also enhanced proliferation over that observed with anti-T3 alone. Sepharose (T3:T4) similarly increased the proliferation of T4+ lymphocytes and a T4+ clone but failed to enhance the proliferation of T8+ lymphocytes. The increased proliferation of T4+ lymphocytes resulted from a preferential activation of the T4+2H4- helper population over the T4+2H4+ suppressor-inducer population. The enhanced proliferation induced by Sepharose (T3:T4) could be completely inhibited by soluble anti-T4. These results suggest that perturbation of T3 may be a minimal signal for T cell activation and that the assembly of a multimeric complex including T3 and T4 may be required for optimal T cell activation. PMID- 3110279 TI - Acquisition of non-MHC restricted cytotoxic function by IL 2 activated thymocytes with an "immature" antigenic phenotype. AB - Culture of human thymocytes in interleukin 2 (IL 2) results in the generation of cytotoxic T lymphocytes (CTL) that kill tumor cell targets without major histocompatibility complex (MHC) restriction. Thymic non-MHC restricted CTL expressed Leu-19 antigen, but were generated from thymic precursor cells that lacked expression of Leu-19. In contrast, short term culture in Il 2 of peripheral blood lymphocytes depleted of Leu-19+ lymphocytes did not result in the generation of cytotoxic activity. IL 2 was necessary and sufficient for the generation of cytotoxic thymocytes and induction of Leu-19 antigen expression. Thymic non-MHC restricted CTL were generated from precursor cells expressing CD1, an antigen present on the majority of thymocytes. Furthermore, cytotoxic activity was detected in IL 2 cultured thymocyte populations with an "immature" antigenic phenotype, i.e. CD1+ and CD4+, CD8+. Upon subsequent culture, thymic non-MHC restricted CTL lost expression of CD1, and developed an antigenic phenotype similar to peripheral blood non-MHC-restricted CTL, suggesting that peripheral non-MHC-restricted CTL may originate from these thymic precursors. PMID- 3110280 TI - A stathmokinetic study of B lymphocytopoiesis in rat bone marrow: proliferation of cells containing cytoplasmic mu-chains, terminal deoxynucleotidyl transferase and carrying HIS24 antigen. AB - In rat bone marrow (BM), the B lineage surface antigen HIS24 is expressed by all surface mu chain-bearing (s mu+) B cells, by cytoplasmic mu chain-containing (c mu+s mu-) pre-B cells and TdT+ cells, and by lymphoid cells lacking both mu and TdT. Because TdT+ and HIS24+TdT-mu- cells may represent stages in B lymphocytopoiesis before mu chain expression, we investigated their kinetics. The metaphase arrest method was combined with immunofluorescence staining to detect proliferation and to quantitate cell production in the BM pre-B, TdT+, and HIS24+TdT-mu- compartments. Their apparent cell cycle times (tC(a)) were 38, 36, and 19 hr, and the number of cells produced per hour per femur were 58, 9, and 41 X 10(4), respectively. The HIS24+ compartments showed further phenotypic heterogeneity. Six percent of TdT+ cells expressed mu chains and were therefore pre-B cells. Twenty percent of HIS24+TdT-mu- cells expressed Ig other than mu chains, with size distribution and kinetics similar to HIS24+TdT-Ig- cells. Thus, the rate of production in the truly Ig-HIS24+ compartment was about 40 X 10(4)/hr/femur (8.5 by TdT+mu- and 33 by TdT-Ig-). In each phenotypic compartment, mitoses were confined to subsets of large (greater than 11 to 12 micron) cells with tC(a) of 13 to 15 hr. Surface mu+ B cells were essentially non cycling. To quantitate whole body BM cell production, the recovery of marrow from bone and the distribution of BM were measured in 59Fe distribution experiments. The number of cells produced by whole body BM was estimated as follows: for pre-B cells, 4.5 X 10(8)/day; for TdT+mu-, 0.7 X 10(8)/day; and for HIS24+TdT-Ig- 2.6 X 10(8)/day. From the derived cell flux in these compartments we suggest that 1) many more pre-B cells are produced than needed by the peripheral B cell pool; 2) if TdT is an obligatory stage in B cell genesis, there must be at least two cell cycles in the pre-B cell compartment; 3) if it is not, the TdT+ stage may be bypassed, with HIS24+TdT-Ig- cells perhaps feeding directly into the pre-B cell compartment. PMID- 3110281 TI - Differential presentation of HLA-DR, DQ, and DP restriction elements by interferon-gamma-treated dermal fibroblasts. AB - IFN-gamma has been reported to induce expression of HLA class II (DR, DQ, DP) antigens on cultured human dermal fibroblasts (FB) by stimulating the de novo transcription of the alpha and beta chain genes of HLA-DR, -DQ, and -DP in these cells. We examined the relative nominal and alloantigen-presentation capacity of each HLA class II gene product on FB by using CD4-positive, TNP-specific T cell clones restricted by determinants on DR, DQ, or DP molecules, as well as allospecific, CD4-positive T cell clones recognizing DR-, DQ-, or DP-lymphocyte activating determinants. After IFN-gamma exposure, FB strains used for antigen presentation displayed a high percentage of DR-positive cells and a much smaller percentage of DP-positive cells, but no detectable DQ-positive cells by immunofluorescent techniques. FB stimulator cells supported proliferative responses of two DR-allospecific T cell clones and one TNP-specific, DR restricted clone, but not another TNP-specific, DR-restricted clone. Despite only modest DP expression, FB stimulated both a TNP-specific, DP-restricted clone and a DP-allospecific T cell line. However, IFN-gamma treated FB failed to stimulate a TNP-specific, DQ-restricted clone and a DQ-allospecific clone. Our data indicate that IFN-gamma differentially regulates expression of functional class II lymphocyte activating determinants on FB antigen-presenting cells and that FB may fail to support DQ-directed T cell responses due to insufficient expression of DQ molecules on the FB cell surface. However, the quantity of DR or DP expressed on FB did not directly correlate with their ability to support T cell responses, indicating that additional factors, such as differences in T cell clone activation requirements, contribute to the capacity of FB to present class II allo- and antigen-restricting epitopes. PMID- 3110283 TI - Autoreactivity accelerates the development of autoimmunity and lymphoproliferation in MRL/Mp-lpr/lpr mice. AB - Lymph node T cells from autoimmune MRL/Mp-lpr/lpr mice, but not from congeneic MRL/Mp-+/+ mice, spontaneously proliferate and produce IL 2 when cultured in vitro for 5 to 7 days. This autologous activation depends critically on the length of in vitro culture and the initial culture density, indicating that cell to cell interaction may be essential. Phenotypic characterization of cultured cells suggests that both L3T4+ and Lyt-2+ T cells proliferate. However, only L3T4+ T cells produce IL 2. Mixing experiments reveal that the inability of freshly isolated lymph node cells from MRL/Mp-lpr/lpr mice to proliferate is not due to the presence of suppressor cells. Supernatant from 7-day cultures failed to induce freshly isolated cells to proliferate. Thus, the failure of freshly isolated cells to spontaneously proliferate and secrete IL 2 is not due to the inability of the cells to produce soluble mediators. Similar to the inactivation of normal T lymphocytes, in vitro addition of monoclonal anti-L3T4 or anti-IL 2 receptor antibody significantly inhibits the activation of these cultured lymphocytes. Spontaneous proliferation and IL 2 production can be blocked by the addition of monoclonal anti-I-Ak but not by monoclonal anti-I-Ad. Spontaneous proliferation and IL 2 production can be detected in young (4-wk-old) MRL/Mp lpr/lpr mice at a time when their lymphocyte composition and physiology appear to be normal. More interestingly, spontaneous proliferation and IL 2 production cannot be detected in C57BL/6J mice bearing the lpr/lpr gene. These experiments support the notion that aberrant syngeneic autoreactivity may act as an accelerating factor in the pathogenesis of lymphoproliferation and autoimmunity in MRL/Mp-lpr/lpr mice. PMID- 3110282 TI - One-signal requirement for interferon-gamma production by human large granular lymphocytes. AB - This laboratory has been investigating IFN-gamma gene expression by highly purified human large granular lymphocytes (LGL) and T cells. We report here that within 1 hr after interleukin 2 (IL 2) treatment of freshly isolated human LGL, IFN-gamma mRNA can be detected, with IFN-gamma protein in the culture medium within 4 to 6 hr of treatment. CD3- Leu-11+ LGL require only a single signal for IFN-gamma production because phytohemagglutinin (PHA), phorbol myristate acetate (PMA), IL 2, or ionomycin can each independently induce IFN-gamma production. In addition, PHA and ionomycin (but not IL 2) show significant synergy with PMA as a stimulus to LGL. In contrast, CD3+ T cells require two stimuli for high levels of IFN-gamma production, and not only are PMA plus ionomycin or PHA synergistic, but in addition, IL 2 and PHA demonstrate some synergy. Furthermore, we have found by fractionation of peripheral blood lymphocytes that IL 2-induced IFN-gamma production is associated with the LGL population and not T cells. These results indicate that with certain stimuli, LGL may be the predominant source of IFN gamma from peripheral blood lymphocytes. PMID- 3110284 TI - Serologically defined V region subgroups of human lambda light chains. AB - The availability of numerous antisera prepared against lambda-type Bence Jones proteins and lambda chains of known amino acid sequence has led to the differentiation and classification of human lambda light chains into one of five V lambda subgroups. The five serologically defined subgroups, V lambda I, V lambda II, V lambda III, V lambda IV, and V lambda VI, correspond to the chemical classification that is based on sequence homologies in the first framework region (FR1). Proteins designated by sequence as lambda V react with specific anti lambda II antisera and are thus included in the V lambda II subgroup classification. The isotypic nature of the five V lambda subgroups was evidenced through analyses of lambda-type light chains that were isolated from the IgG of normal individuals. Based on analyses of 116 Bence Jones proteins, the frequency of distribution of the lambda I, lambda II/V, lambda III, lambda IV, and lambda VI proteins in the normal lambda chain population is estimated to be 27%, 37%, 23%, 3%, and 10%, respectively. This distribution of V lambda subgroups was comparable to that found among 82 monoclonal Ig lambda proteins. Considerable V lambda intragroup antigenic heterogeneity was also apparent. At least two sub subgroups were identified among each of the five major V lambda subgroups, implying the existence of multiple genes in the human V lambda genome. The V lambda classification of 54 Ig lambda proteins obtained from patients with primary or multiple myeloma-associated amyloidosis substantiated the preferential association of lambda VI light chains with amyloidosis AL and the predominance of the normally rare V lambda VI subgroup in this disease. PMID- 3110285 TI - Structural analysis of an HLA-B27 population variant, B27f. Multiple patterns of amino acid changes within a single polypeptide segment generate polymorphism in HLA-B27. AB - The structure of a new HLA-B27 variant, B27f, distinguishable from other HLA-B27 subtypes by isoelectric focusing and serologic criteria, has been established by comparative peptide mapping and radiochemical sequence analysis. HLA-B27f differs from the major B27.1 subtype in three clustered amino acid replacements: Asp74, Asp77, and Leu81 in B27.1 are changed to Tyr74, Asn77, and Ala81, respectively in B27f. This pattern of differences is analogous to that of HLA-B27.2 in that this subtype also differs from B27.1 in multiple clustered substitutions within the same segment. Thus, polymorphism within the HLA-B27 system is being achieved by introducing different sets of amino acid changes within a particular short segment of the alpha 1 domain. The most likely mechanism for the introduction of multiple changes within this segment is a nonreciprocal recombination event, such as gene conversion. The structural analogies and ethnic distribution of B27f and B27.2 as compared with those of B27.3, and B27.4 support a dynamic model of HLA B27 evolution in which polymorphism has been created after the separation of the major ethnic groups. In this model, a Caucasian branch would be characterized by subtypes differing from B27.1 in a few changes within the alpha 1 domain, which were probably generated by single genetic steps. An Oriental branch would include those subtypes which differ from B27.1 by changes in both alpha 1 and alpha 2, involving multiple genetic steps for their generation. PMID- 3110286 TI - Co-sedimentation of chondroitin sulfate A glycosaminoglycans and proteoglycans with the cytolytic secretory granules of rat large granular lymphocyte (LGL) tumor cells, and identification of a mRNA in normal and transformed LGL that encodes proteoglycans. AB - Rat large granular lymphocyte (LGL) tumor cell lines were analyzed for the presence of proteoglycans and glycosaminoglycans in their cytolytic secretory granules. When isolated rat LGL tumor cells were incubated in vitro for 1 to 3 hr with [35S]sulfate, and the 35S-labeled macromolecules were purified by density gradient centrifugation, they filtered on Sepharose CL-4B columns predominantly as approximately 500,000 m.w. macromolecules. After 19 hr of incubation with [35S]sulfate, however, an 85,000 m.w. species predominated. Pulse-chase experiments revealed that the larger macromolecules were proteoglycans that with time were processed to glycosaminoglycan-sized macromolecules. As assessed by their susceptibility to chemical and enzymatic degradation and by high pressure liquid chromatography of the chondroitinase ABC-generated unsaturated disaccharides, the cell-associated rat LGL tumor cell proteoglycans bore almost exclusively chondroitin sulfate A glycosaminoglycans. Northern blot analysis using a gene-specific probe revealed that both normal peripheral blood and transformed rat LGL expressed the same approximately 1.3-kb mRNA that encodes the peptide core of the proteoglycans in the secretory granules of rat and mouse mast cells. In vivo radiolabeling of rat LGL tumor cells and isolation of their intact granules after nitrogen cavitation and density sedimentation established that glycosaminoglycans compartmentalized with cytolytic activity. Thus these negatively charged macromolecules may play a role in the regulation of the packaging and delivery of the cytolysins and basically charged serine proteases that have been identified in the cytolytic secretory granules of LGL. PMID- 3110288 TI - Correlation of immunogenicity and production of ornithine by peritoneal macrophages. AB - The release of ornithine by macrophages and its correlation with their immunogenicity after treatment with various macrophage-stimulating substances were analyzed. Pristane-elicited peritoneal macrophages (PM) were found to express strong arginase activity and to release L-ornithine into the extracellular space. This activity is strongly reduced within 3 hr after treatment with tetradecanoylphorbol acetate (TPA) but not with lipopolysaccharide (LPS). Resident PM usually express little arginase activity, but this activity is markedly augmented within 24 or 48 hr after treatment with LPS. The release of ornithine by peritoneal cells (PC) (60 to 90% macrophages) was found to be correlated with their immunogenicity as determined by the in vivo immunization for a subsequent in vitro secondary cytotoxic response against minor H antigens. The immunogenicity of pristane-elicited PC is markedly stronger than that of resident PC or TPA-treated, pristane-elicited PC. Moreover, the immunogenicity of the resident PC and TPA-treated elicited PC is substantially augmented by the simultaneous injection of ornithine, whereas the immunogenicity of the untreated elicited PC is not further augmented by exogenous ornithine, indicating that the endogenous production of ornithine by the stimulating cells had a strong influence on the resulting immune response. Injection of glutathione into pristane-treated mice also reduces the ornithine production and immunogenicity of the resulting peritoneal exudate cells. The immunogenicity in this case is at least partly reconstituted by application of exogenous ornithine. Our experiments revealed no correlation between the production of ornithine and prostaglandin E2. Prostaglandin E2 production of resident and pristane-elicited PC is not markedly different and is in either case strongly augmented by TPA. Elicited or resident PM which have been incubated for several days in culture release practically no ornithine; but ornithine production can be induced again by incubation for 24 hr with LPS and to some extent also with interferon-gamma. PMID- 3110287 TI - Prostaglandin synthesis and release by subpopulations of rat alveolar macrophages. AB - Alveolar macrophages are the primary phagocytic cell of lung, but are also capable of a variety of other functions, which include initiating or modulating inflammatory and immune responses through the production of soluble mediators. One such group of mediators is the eicosanoids. Further, recent data indicate that alveolar macrophages are not functionally homogeneous, but are heterogeneous with several subpopulations that differ both morphologically and functionally. Considering the apparent importance of prostaglandin synthesis and release in inflammatory and immune responses, the current study was undertaken to determine whether alveolar macrophage subpopulations differ in their ability to synthesize and release prostaglandin (PG) E, PGI2, and thromboxane A2 after stimulation by calcium ionophore A23187, zymosan, or aggregated IgG. Alveolar macrophages were harvested by bronchoalveolar lavage and were separated into 18 density-defined fractions. Density-defined alveolar macrophages (DD-AM) showed marked heterogeneity in prostaglandin synthesis and release. Maximal PGE synthesis and release was seen as a single peak after calcium ionophore A23187 and zymosan stimulation. In contrast, two peaks in PGE synthesis were seen after aggregated IgG stimulation. PGI2 synthesis was seen as a single peak generated by different DD-AM after calcium ionophore A23187 and zymosan. In contrast, aggregated IgG stimulation of subpopulations exhibited uniform synthesis and release of PGI2. Thromboxane A2 synthesis and release was maximal from a broad range of various DD AM after calcium ionophore A23187, zymosan, and aggregated IgG stimulation. The results demonstrate that DD-AM are heterogeneous in ability to synthesize and release prostaglandins which is dependent on the stimuli. Therefore, specific subpopulations of alveolar macrophages may be central to the control of the pulmonary inflammatory response through specific eicosanoid synthesis and release. PMID- 3110289 TI - Stimulation of mouse lymphocytes by a mitogen derived from Mycoplasma arthritidis. VI. Detection of a non-MHC gene(s) in the E alpha-bearing RIIIS mouse strain that is associated with a specific lack of T cell responses to the M. arthritidis soluble mitogen. AB - Previous work using inbred, congenic and recombinant mouse strains showed a positive association with expression of E alpha and the ability of splenic cells to bind to and undergo proliferation in response to a T cell mitogen present in culture supernatants of Mycoplasma arthritidis (MAS). Studies described in the present manuscript confirm this association because lymphocytes from mice expressing H-2a, H-2d, H-2j, H-2k, H-2p, H-2u, and H-2v all of which possess E alpha responded to MAS, whereas those expressing H-2b, H-2f, H-2q, and H-2s, which lack E alpha, failed to respond. One exception was noted in that the inbred RIIIS mouse (H-2r) that expresses E alpha failed to respond to MAS but responded normally to concanavalin A, and phytohemagglutinin. In contrast, the congenic B10.RIII (H-2r) mouse did respond to MAS, suggesting the presence of an MAS nonresponsive, non-major histocompatibility complex (MHC) gene(s) in the RIIIS mouse. MAS nonresponsiveness in the RIIIS mouse was recessive because the lymphocytes from F1 crosses with responder B10.RIII (H2r) and C3H (H2k) mice responded to MAS. Analysis of (RIIIS X B10.RIII)F1 X RIIIS or B10.RIII parental test cross progeny confirmed that nonresponsiveness to MAS was associated with a recessive, non-MHC gene(s). Evidence was also found that a non-MHC, MAS nonresponsive gene(s) is also present in the inbred SWR (H-2q) and SJL (H-2s) strains, because lymphocytes from F1 crosses between these strains and the RIIIS mouse failed to respond to MAS. Both RIIIS and B10.RIII splenic cells bound the mitogen in MAS to a similar degree, confirming the presence of the binding site in both mice. In contrast, C3H.SW (H-2b) splenic cells that do not express E alpha failed to bind the mitogen. The nonresponsiveness of RIIIS lymphocytes to MAS was exercised at the level of the T cell rather than the accessory cell. Thus RIIIS T cells failed to respond to MAS presented by RIIIS, B10.RIII, or (RIIIS X B10.RIII)F1 accessory cells. In contrast, B10.RIII and (RIIIS X B10.RIII)F1 T cells responded to MAS when presented by RIIIS, B10.RIII, or F1 accessory cells. Similar observations were made using SWR and SJL T cells, which failed to respond to MAS irrespective of the source of accessory cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3110290 TI - Distinct mechanisms regulate MHC class II gene expression in B cells and macrophages. AB - In a previous series of studies, we had shown that the constitutive Ia expression in an immunoselected Ia-human B cell variant, RJ 2.2.5, could be restored by somatic cell hybridization with mouse B cells. These experiments allowed us to show the existence of a transacting activator factor(s) operating across species barriers and encoded by the aIr-1 locus located on mouse chromosome 16. The aim of the present study was to investigate whether the B cell constitutive Ia expression and the inducible Ia expression, as seen in macrophages treated with IFN-gamma, are controlled by similar intracellular factors. To this purpose, we constructed an interspecies somatic cell hybrid between the human Ia-RJ 2.2.5 B cells and the mouse Ia-P388 D1 macrophage cells. These murine cells transiently express Ia antigens when incubated with IFN-gamma. Our results show that RJ 2.2.5 X P388 D1 cell hybrids do not express either human or mouse class II gene products. Treatment with human recombinant IFN-gamma did not modify the MHC phenotype of either the hybrid cells or the human parental cells. On the other hand, treatment of the hybrid cells with murine recombinant IFN-gamma resulted in de novo expression of mouse Ia mRNA and corresponding cell surface antigens without, however, reinduction of the human class II-positive phenotype. Furthermore, treatment with the mouse lymphokine significantly increased the levels of human HLA class I mRNA and corresponding cell surface antigens in the hybrid cells, further reinforcing the notion of the existence of non-species specific secondary mediators generated after receptor-ligand interaction in the IFN-gamma system. Together, these results indicate that in macrophages, the intracellular events taking place after binding of IFN-gamma with its own receptor and leading to the expression of a class II-positive phenotype do not operate via an activation of the aIr-1 locus and/or its products. Thus, at least in our experimental system, we can firmly establish a first, relevant distinction between constitutive and inducible class II gene expression. This difference, dictated by the specific differentiation program of each cell type, may be relevant for the understanding of the function of class II gene products. PMID- 3110291 TI - Modulations of functional activity in differentiated macrophages are accompanied by early and transient increase or decrease in c-fos gene transcription. AB - Marked changes in c-fos proto-oncogene mRNA level and transcription rate were observed upon modulation of the functional activity of cultured mouse peritoneal macrophages. Cholera toxin (CT), dexamethasone (dex), interferon-gamma (IFN gamma), concanavalin A (Con A), and endotoxin (LPS) induced changes in mRNA levels and transcription rates of both urokinase-type plasminogen activator and tumor necrosis factor/cachectin genes, the products of which are sensitive indices of macrophage activity. All of these agents also caused rapid and transient changes in c-fos gene expression, either enhancement (CT, dex, and LPS) or decrease (IFN-gamma and Con A). Moreover, inhibition of protein synthesis elicited a transient increase in the level of c-fos gene transcription, suggesting that the transcriptional activity of the c-fos gene is controlled by labile protein repressor(s). Taken together, these results suggest a possible role for the c-fos gene product, a nuclear protein, in the modulation of the functional activity of differentiated macrophages. PMID- 3110293 TI - The characterization of a human B cell line utilizable for the assay of B cell growth factors. AB - An EBV-transformed B cell line JR-2(82) is described which proliferates in response to human B cell growth factor (BCGF) preparations. Although spontaneous replication occurs at high cell densities, at cell densities of 10(3) cells or less, cell death occurs in the absence of BCGF. This response is not dependent upon the presence of low concentrations of supplemental serum in the culture medium. There is no proliferative response to various preparations of interleukin (IL)-1, IL-2 or gamma-interferon (gamma-IFN) up to 1000 U/ml either alone or in combination and specific antisera to IL-2 and gamma-IFN do not interfere with the proliferative response. At 5000 U/ml of gamma-IFN or greater, a partial proliferation of the line is seen to 30% of maximal. The JR-2(82) line and its clones appear to proliferate preferentially in response to low molecular weight (LMW) BCGF, compared to the response seen to high molecular weight (HMW) BCGF from Namalwa cell line supernatants. The line does not produce Ig spontaneously but on incubation with B cell differentiation factor (BCDF) containing supernatants differentiates to an IgG-producing cell line. JR-2(82) or its derivatives may therefore provide a simple reproducible assay for BCGF in the presence of other lymphokines and may be used to study further the interactions of lymphokines in the regulation of the proliferation of EBV-transformed cells. PMID- 3110292 TI - Resistance to the cytolytic action of lymphotoxin and tumor necrosis factor coincides with the presence of gap junctions uniting target cells. AB - The resistance of target cells to the cytolytic action of lymphotoxin (LT) and recombinant tumor necrosis factor (rTNF) has been investigated by using clonally derived cell lines with defined gap junction-mediated, intercellular communication properties. Gap junction-competent Chinese hamster ovary cells are normally insensitive to the action of LT/TNF. However, treatment with 12-o tetradecanoylphorbol-13-acetate, which promotes the loss of gap junctions, or culturing at low cell density to reduce intercellular contacts, significantly increased their sensitivity to LT/TNF. The LT/TNF-sensitive murine CL-1D and L929 cell lines, which in normal culture conditions are unable to form gap junctions, were not changed in their susceptibility to LT/TNF after treatment with phorbol ester or low culture density. However, the formation of gap junctions by CL-1D can be promoted by treatment with 8-bromo-cyclic adenosine monophosphate (1 mM), and this treatment completely suppressed the ability of LT and rTNF to kill CL 1D. Additionally, the LA25-normal rat kidney cell line, which is infected with a temperature-sensitive mutant of Rous sarcoma virus (LA25), is gap junction competent and resistant to the effects of LT at the restrictive temperature (39 degrees C). However, when shifted to the permissive temperature (33 degrees C), LA25-normal rat kidney cells express the pp60v-src viral gene product, lose their ability to form gap junctions, and become sensitive to the lytic activity of LT. The results demonstrate that the expression of the retroviral pp60v-src, a tyrosine protein kinase, is sufficient to render cells susceptible to the lytic effects of LT and rTNF. Collectively, these experiments demonstrate a strong correlation between the resistance of target cells to the action of LT/TNF and their ability to cooperate metabolically through gap junctions. The results do not completely exclude the possibility that other mechanisms, such as LT receptor modulation, are also occurring under these experimental conditions. These data also suggest that a possible physiologic function of the stable cytotoxic lymphokines is to induce cytolysis/cytostasis of cells that have lost gap junctional contact, such as those in the process of mitosis or metastasis that have separated from the main tissue mass. PMID- 3110294 TI - Improvement in the basic technology of electrofusion for generation of antibody producing hybridomas. AB - In order to define the optimum conditions of electrofusion technique for the generation of antibody-producing hybridomas, mouse spleen cells or EBV transformed human B cells were fused with mouse myeloma cells (SP2/0) or human fusion partner cells (KR-4 or KR-12), respectively, by electric field pulse under various conditions. The results confirm reports that the presence of both Ca2+ and Mg2+ in fusion medium and pretreatment of mixed cells with proteases improve hybridoma yield. Moreover, the presence of liposome or hydrophobic protein in the fusion medium greatly enhanced the yield. Under optimum conditions, hybridoma yields of mouse cells and human cells were 2.5 X 10(-4) and 1 X 10(-4), respectively. These efficiencies were about ten times higher than those obtained by the conventional polyethylene glycol technique. Microscopic observation of the fusion-process revealed that in a human cell system 20%-50% of the cells were physically fused, although only one in 5000 physically fused human cells grew as a hybridoma after hypoxanthine-aminopterin-thymidine selection. PMID- 3110295 TI - An ELISA that detects cell-associated and released rat IL-2 receptors in a soluble form. AB - A mouse anti-rat interleukin-2 receptor (IL-2R) monoclonal antibody (mAb), ART 65, has recently been developed which recognizes the rat IL-2R but binds to an epitope distinct from that recognized by the mAb ART-18. The availability of two mAb against the rat IL-2R molecule permitted the development of an enzyme-linked immunosorbent assay (ELISA) which detects soluble and solubilized rat IL-2R. Using this ELISA, time course studies of ConA and LPS-activated rat splenocytes revealed that IL-2R are released into their environment during the culture period, and that IL-2R can be detected in rat sera. The significance of the results is discussed. PMID- 3110296 TI - Antibody-bearing liposomes as multicolor immunofluorescence markers for flow cytometry and imaging. AB - Liposomes covalently coupled to monoclonal antibodies retain the specificity of the antibody and bind only to cells bearing the appropriate determinant. As opposed to directly labeled antibodies which generally have fluorochrome to protein ratio of between 2-5, the entrapped space inside liposome can contain several hundred to several thousand molecules of fluorochromes in a space chemically isolated from the outside environment, thus providing the potential for an amplified fluorescence signal. We have prepared small unilamellar liposomes containing the soluble fluorochromes carboxyfluorescein (CF), which fluoresces in the green and sulforhodamine (SR), which fluoresces in the red, and covalently coupled a series of monoclonal antibodies using a heterobifunctional reagent. We were able to detect, on an Epics 753 flow cytometer equipped with an argon ion and a dye laser and by fluorescence microscopy, both single and double labeled mouse spleen lymphocyte subsets, fibroblast L cells and Raji cells. Complete color separation was obtained with CF-labeled cells being detected only by the green photomultiplier and SR-labeled cells by the red photomultiplier. Cells labeled with both were detected by both photomultipliers. Liposomes bearing anti-Ia antibodies bound only to B lymphocytes whereas those with anti-H-2K antibody bound both to T and B lymphocytes. In another system, single and dual color immunofluorescence made possible the simultaneous detection of HLA and H-2K molecules on transfected murine fibroblast L cells. The signal-to-noise ratio was more favorable for the liposome-labeled reagents than reagents labeled with fluorescein isothiocyanate. Cells labeled with antibody-bearing liposomes could be fixed with paraformaldehyde or glutaraldehyde without adversely affecting the original staining patterns. Apart from the two fluorochromes described above, other markers of choice could be encapsulated without any adverse effect on the antibody-liposome coupling procedure or on the specificity of the conjugated antibody. Since the fluorochrome is not directly coupled to the protein, there is no requirement for protein conjugation sites in order for it be usefully encapsulated inside liposomes. Therefore, this system provides new opportunities to exploit different, as yet untapped fluorochromes for use in flow cytometry and imaging. PMID- 3110297 TI - Inhibition of melanization in human melanoma cells by a serotonin uptake inhibitor. AB - Significant levels of intracellular catecholamines were found in a human melanoma cell line and were enhanced by increasing the extracellular tyrosine concentration. Intracellular dopa, 5-cysteinyldopa, tyrosinase, and melanin also rose under these conditions. 5-HT (serotonin) was synthesized by the melanoma cells but further study was hindered by the high level of 5-HT in fetal calf serum. A 5-HT uptake antagonist, DU 24565 (6-nitroquipazine), was employed as an alternative method for studying 5-HT action. This compound, which in contrast to tunicamycin had no inhibitory effects on cell proliferation or tyrosinase activity, strongly inhibited melanization and decreased the levels of dopa, 5 cysteinyldopa, dopamine, noradrenaline, adrenaline, and 3,4-dihydroxyphenylacetic acid. DU 24565 had little effect on 5-HT or tyrosine accumulation in these cells but suppressed the uptake of extracellular dopa. The results show that human melanoma cells synthesize a wide range of biogenic amines in culture and suggest a new approach to regulating intracellular levels of dopa and of a variety of dopa products. PMID- 3110298 TI - Interferon-induced cytolysis correlates with the degree of transformation of epidermal cells. AB - The cytolytic activity of interferon (IFN) was evaluated for its ability to distinguish between paired sets of nontumorigenic/tumorigenic epidermal cells (JB 1/JB-8; D1/D11a) as well as a set consisting of nonpromotable, promotable, and tumorigenic epidermal cell lines (JB-6 clones 30, 21, and RT101). The viability of the cell types was measured in a microassay using histoplates. IFN-gamma and IFN-alpha/beta, when employed singly, demonstrated an equivalent and limited effect on the viability of all cell lines. Treatment of nontumorigenic and nonpromotable cell lines with the combination of IFN-gamma + IFN-alpha/beta also caused only a limited effect on cell viability, whereas treatment of tumorigenic and promotable cell lines with the combination of IFNs caused a marked decrease in cell viability. Thus, the cytolytic effect of IFNs employed in combination but not singly was discriminatory between tumorigenic and nontumorigenic cells as well as between promotable and nonpromotable cells. Addition of cytotoxic effector cells was found to have a relatively moderate effect on the survival of target cells that were treated with IFN-gamma or IFN-alpha/beta separately. Addition of cytotoxic effectors to target cells treated with the IFNs in combination had a discriminatory effect. Nontumorigenic and nonpromotable cells were moderately affected; the tumorigenic and the promotable cells, however, were markedly affected, resulting in their complete (or nearly complete) eradication. The results demonstrate that combination IFN treatment: has a discriminatory cytolytic effect on tumorigenic and promotable cells in contrast to their nontumorigenic and nonpromotable counterparts; and when added to cytotoxic effector cells can completely eradicate tumorigenic and promotable cells while having a significantly lesser effect on nontumorigenic and nonpromotable cells. PMID- 3110299 TI - Human epidermal Langerhans cells internalize by receptor-mediated endocytosis T6 (CD1 "NA1/34") surface antigen. Birbeck granules are involved in the intracellular traffic of the T6 antigen. AB - Using immunogold staining of a suspension of living human epidermal cells to identify the Langerhans cell membrane-associated antigen T6 (revealed by the monoclonal antibody BL6), we have observed internalization of T6 antigen in Langerhans cells. This phenomenon is at least partly due to receptor-mediated endocytosis involving coated pits, coated vesicles, endosomes, the smooth endoplasmic reticulum, and lysosomes. These ultrastructural results suggest that T6 antigen may be part of a receptor site. Following receptor-mediated endocytosis, the appearance in the cell center of the first labeled Birbeck granules suggests that Birbeck granules could represent T6 intracellular transport organelles carrying T6 from the central part of the cell to an unknown destination. PMID- 3110300 TI - Absence of Langerhans cells in oral hairy leukoplakia, an AIDS-associated lesion. AB - Oral hairy leukoplakia (HL) is a recently described manifestation of human immunodeficiency virus (HIV) infection in which Epstein-Barr virus (EBV) has been shown to replicate. To seek evidence for a local defect in mucosal immunity, we assessed the presence of epithelial Langerhans cells (LC) in these lesions and in autologous nonlesional mucosa. We used monoclonal antibodies against HLA-DR, HLA DQ, and T6 antigens to identify LC in biopsy specimens of HL from 23 homosexual men. In all lesion specimens, LC either were not detected or were present only in greatly reduced numbers with at least 1 of the antibodies. In nonlesional oral mucosa from the same patients, LC were detected with all 3 antibodies in 11/12 specimens (92%) and were found in approximately normal numbers with at least 1 antibody. There was close correlation between the absence of LC and positive staining for EBV, human papillomavirus antigens, and candidal hyphae in the epithelium. We conclude that LC are absent or greatly reduced in the lesions of HL. Absence of normal LC function may be important in the pathogenesis of HL and may reflect an event in the pathogenesis of other features of the acquired immune deficiency syndrome. PMID- 3110302 TI - Bactericidal activity for Neisseria meningitidis in properdin-deficient sera. AB - We investigated serum bactericidal reactions against Neisseria meningitidis (serogroups A, B, C, D, Y, W-135, 29E, X, and Z) in the sera of two healthy adults with properdin deficiency. Bactericidal reactions mediated via the classic complement pathway (unchelated system) were not impaired in properdin-deficient serum. The properdin-deficient sera supported alternative pathway-mediated killing (Mg++EGTA-chelated system) of some, but not all, of the strains investigated. Vaccination of the properdin-deficient individuals with serogroup A and C polysaccharide clearly increased the concentrations of antibody to meningococci. At least some of the antibodies induced by vaccination supported the bactericidal activity of properdin-deficient serum. Some antibodies to meningococci, probably of the IgM class, promoted alternative pathway-mediated bactericidal reactions in the absence of properdin. By contrast, presensitizing meningococci with IgG enhanced the alternative pathway-mediated reactions, but this was strictly a properdin-dependent effect. PMID- 3110301 TI - A long-term clinicopathologic survey of patients with Jessner's lymphocytic infiltration of the skin. AB - Skin biopsies from 6 patients with Jessner's lymphocytic infiltration (JLI) were studied using monoclonal antibodies in peroxidase staining, on some occasions combined with [3H]thymidine incorporation visualized by autoradiography. Ninety one +/- two percent of all inflammatory mononuclear cells in situ were T11 positive T lymphocytes, whereas B lymphocytes were few. Forty-nine +/- nine percent of cells were Ia-positive, suggesting involvement of T cells in the local pathogenetic mechanisms, but interleukin-2 receptor-carrying cells as well as [3H]thymidine-incorporating cells accounted for less than 2% of all inflammatory cells, suggesting that T blasts account for only a small minority. Similarly, PCA 1 plasma cells were few in situ, there was no immunoglobulin or complement deposition at the dermal-epidermal junction and serum antinuclear and anti-DNA antibodies as well as complement levels were normal, and no visceral involvement was revealed during the survey period. According to our findings, JLI of the skin seems to be sufficiently distinctive to be appreciated as an entity. T lymphocytes in JLI do not seem to proliferate in the site of inflammation but are merely accumulated from the circulation. PMID- 3110303 TI - Use of bovine milk concentrate containing antibody to rotavirus to treat rotavirus gastroenteritis in infants. AB - The use of a concentrate containing milk immunoglobulins prepared from rotavirus hyperimmunized cows (neutralization titer, 1:6,000 for a 10% solution) to treat infants hospitalized for acute rotavirus gastroenteritis resulted in a significant (P = .008) reduction in the duration of excretion of virus. Stool samples from treated infants showed the presence of bovine milk immunoglobulins in 47% of cases and of neutralizing activity in 43% (mean neutralization titer, 1:48); stool samples from control infants showed neutralizing activities in only 3% of cases (neutralization titers, less than 1:20). Immunoelectrophoresis of stool extracts revealed fragment A, a bovine analogue of F(ab')2 or Fab, as the major product of in vitro and in vivo digestion of the immunoglobulins. Cessation of excretion of virus correlated with the appearance of neutralizing activities in 19 of 25 infants. Only concentrate-treated infants with high neutralizing activity in stools showed a statistically significant reduction in duration of excretion of virus; this duration in concentrate-treated infants with low neutralizing activity was comparable with controls. PMID- 3110304 TI - Ceftriaxone transport through the blood-brain barrier. PMID- 3110305 TI - Efficacy of ciprofloxacin in the treatment of nasopharyngeal carriers of Neisseria meningitidis. PMID- 3110306 TI - Prevalence of urethral Chlamydia trachomatis and Neisseria gonorrhoeae among asymptomatic, sexually active adolescent boys. PMID- 3110307 TI - Prevention of endemic icteric viral hepatitis by administration of immune serum gamma globulin. AB - In a further analysis of a randomized, double-blind study of 107,803 U.S. soldiers receiving either immune serum gamma globulin (ISG) or placebo, serum specimens from the first week of clinical illness from 210 soldiers consecutively hospitalized with icteric hepatitis were reexamined by using modern immunologic methods to test for evidence of hepatitis A and B. Prophylactic intramuscular injection of 5 or 10 ml of ISG containing antibody to hepatitis A virus and antibody to hepatitis B surface antigen provided significant protection against development of endemic type A, type B, and non-A, non-B icteric hepatitis for six months if it was administered before exposure. Failure to receive a second injection of either 5 or 10 ml of ISG permitted an occurrence of hepatitis that was not significantly different from that among subjects who failed to receive a second placebo injection. ISG at 2 ml appeared equally effective in preventing hepatitis A but may be less effective in preventing hepatitis B and non-A, non-B hepatitis. PMID- 3110308 TI - Effects of antifungal agents and gamma interferon on macrophage cytotoxicity for fungi and tumor cells. AB - The activated macrophage may play a central role in host effector mechanisms against invading fungi. Here we demonstrate the importance of the activation state of murine macrophages for both fungistatic and fungicidal activity. Host factors such as gamma interferon and microbial products such as endotoxin can interact synergistically to initiate this cytotoxicity. This activated state may be aided by antifungal agents such as amphotericin B. Both a methyl ester derivative of amphotericin B and liposomal amphotericin B Both a methyl ester derivative of amphotericin B and liposomal amphotericin B potentiated macrophage activation but were less potent than amphotericin B. Other available antifungal agents such as azole compounds and flucytosine did not possess this ability to interact with the intrinsic macrophage effector mechanisms. However, ketoconazole and itraconazole avidly bind to macrophages as the biologically active drug. The azole-loading of macrophages may be a factor in macrophage cytotoxicity for fungi. PMID- 3110309 TI - Six cases of Mycobacterium tuberculosis bacteremia. PMID- 3110310 TI - Systemic infection with Malassezia furfur in an adult receiving long-term hyperalimentation therapy. PMID- 3110311 TI - AIDS and the oral cavity. The HIV-infection: virology, etiology, origin, immunology, precautions and clinical observations in 110 patients. PMID- 3110312 TI - Le Fort fractures (I). A study of frequency, etiology and treatment. AB - The cause and frequency of maxillary fractures as well as type of treatment performed has been reviewed in this study. During the time period between 1969 and 1982, a total of 301 maxillary fractures have been treated at our Department of Oral and Maxillofacial Surgery in Gothenburg. The period has been subdivided in 3 parts to evaluate whether differences in the amount of severe fractures could be observed. Since a law was instituted in Sweden in 1975 calling for a mandatory use of front seat belts, the frequency of fractures related to the time periods before and after 1975 could be of interest. We found a surprisingly equal number of fracture incidents during the different periods of time, but a decreasing number of maxillary fractures of type le Fort I, II and III; partial maxillary fractures on the other hand, had increased in number. PMID- 3110313 TI - Management of mandibular fractures in the highlands of Papua New Guinea. AB - The Management of fractured mandibles presenting in the Highlands of Papua New Guinea (PNG) is described and discussed. Features of management in this situation included: a longer period of prefixation conservative treatment; the elective use of local anaesthesia for all but the occasional operative procedure; a more aggressive attitude towards traumatised or infected teeth lying in fracture sites; confining all those patients in intermaxillary fixation or those receiving systemic medication to the hospital for the total duration of the treatment. Treatment was required to be compatible with the special problems of an unsophisticated patient population with delay in presentation, plus absence of adequate follow-up, with therapy being carried out in a hospital environment lacking specialist facilities. PMID- 3110314 TI - The bony lid approach for the apical root resection of lower molars. AB - The apical root resection of mandibular molars is an operation seldom performed and then one limited primarily to the lower first molars. Although the first paper on this topic was published at the beginning of the 20th century, little progress has been observed since then. This is due to the thickness of the buccal bony plate in the lower molar region which makes surgery very difficult and leads to a substantial loss of bone. The resultant limitation of the operating field prevents good vision. The aim of our approach is to minimize or to eliminate these problems by opening a bony lid above the roots which are to be resected. This can be made large enough for the surgeon to have easy access and good vision during apical surgery. At the end of the operation the same lid is replaced in order to avoid a bony defect and to facilitate the healing process. Of the 75 patients treated using this technique during a 3-year period, only one post operative complication has been observed. A complete healing of the bone was observed in the majority of cases within 6 months. PMID- 3110315 TI - Tinidazole or pivampicillin in third molar surgery. AB - There is an increasing body of evidence implicating oral anaerobic bacteria in the aetiology of post-surgical dentoalveolar infections. This information has lead to several studies demonstrating the usefulness of specific anaerobicidal drugs in the prevention and treatment of dento-alveolar infection. One such study utilised a single 2 g preoperative oral dose of tinidazole which was found to be significantly better than placebo in preventing infective sequelae after removal of impacted mandibular third molars. The present study was designed to compare a high-dose short-term broad spectrum penicillin, (pivampicillin), with the previously described regimen, using tinidazole in order to discern the existence or otherwise of any practical difference between an anaerobicidal and a broad spectrum antibiotic when local infection was considered. PMID- 3110316 TI - Fibrinolytic alveolitis and its prevention. AB - This study aimed at testing the clinical efficacy of a topical prevention of FA, the sample comprising 300 cases of extractions. A sponge was inserted in the socket of each of them, dividing the sample into 3 equal groups: group A (gelatine), group B (gelatine + Solcoseryl) and group C (gelatine + Solcoseryl + propyl-hydroxy-benzoic-acid). The global incidence of FA was a comparatively high, 7.6%, which could be related to the pool of patients included in the study as to the presence of teeth and techniques more prone to complications. No specific clinical characteristic has been isolated (distribution within sex, age, teeth, etc.) which could contradict data collected from other authors. The incidence was lower in the groups B (3%) and C (7%) as compared to group A (13%), but only sponges of group B demonstrated a clinical and statistical efficacy, according to the high number of lower third molar extractions. In contrast, the addition of Solcoseryl proves efficient and does not delay healing, according to previous histological studies. This last characteristic has to be confirmed in the experimental conditions described in our study, as has its mode of action. The ultimate mechanism of FA has still, in our opinion, to be better defined well before the restatement of a topical prevention of FA. PMID- 3110317 TI - Tooth loss among Nigerians: causes and pattern of mortality. AB - A study was carried out to elucidate the causes and pattern of loss of permanent teeth among Nigerians. A total of 3,163 dental extractions were carried out on 2,100 patients thus giving a ratio of 1.5 extractions per patient. The investigation revealed two major causes of tooth loss, i.e. periodontal disease (46.4%) and dental caries (43.9%). Other important aetiologic factors were trauma (4.5%), tooth impaction (2.4%) and orthodontic problem (1.6%). There was evidence to confirm fears by previous researchers that dental caries as a major cause of tooth mortality was increasing fast and could soon become the most important cause of tooth loss if not controlled. The study further showed that tooth mortality among Nigerians could be minimized if appropriate steps were taken immediately to control periodontal disease and dental caries, both of which constitute approximately 90% of all the causes of tooth loss. PMID- 3110318 TI - Physostigmine reversal of drug-induced paradoxical excitement. AB - Paradoxical excitement associated with intravenous conscious-sedation in a patient undergoing dental surgery was successfully reversed with 1.0 mg physostigmine. Physostigmine is felt to have exerted this effect by 2 mechanisms: the re-establishment of homeostasis in the CNS via augmented cholinergic pathways with the net result being thalamacocortical excitation, and cholinergically mediated increase in cerebral blood flow increasing the rate of redistribution of the intravenous sedative agents used. The most commonly encountered side-effects of physostigmine used to reverse parodoxical excitement, emergence delirium, or prolonged narcosis are bradycardia, nausea, and/or vomiting. The incidence of these side-effects is low in doses, below 2.0 mg/70 kg. body weight. PMID- 3110319 TI - Effect of corticosteroid and sodium hyaluronate on induced joint lesions in the guinea-pig knee. AB - 50 guinea-pigs had lesions induced in their knee-joints by intra-articular injections of papain solution (2%). The lesions developed were treated with intra articular injections of corticosteroid (Celestona bifas) in the right and sodium hyaluronate (Hylartil) in the left knee. The treatment was repeated after 1 week. 5 months later, the joints were examined macroscopically, microscopically and radiographically. Comparison of the effects of treatment showed that early treatment with hyaluronate resulted in less deviation in form of the joint, and less granulation tissue formation but no significant difference in the overall severity of the lesions was found. Granulation tissue, fibrotic adhesions and inflammation in the synovial membrane induced in the experimental model were positively correlated to cortical bone destruction. PMID- 3110320 TI - Peripheral ameloblastoma with metastasis. AB - Peripheral ameloblastoma is an uncommon clinical entity, while ameloblastoma with distant metastasis is still more unusual. A case of peripheral ameloblastoma with left supraclavicular lymph node metastasis is presented here. PMID- 3110321 TI - Osteosarcoma of the jaws--a series from Kaduna, Nigeria. AB - 15 primary and one metastatic osteosarcoma of the jaw bones in Nigerians are described. The age range was typical of this tumour; most cases were in the mandible. Clinical and radiographic features were often diagnostic but the microscopic appearances were varied and problematical. No metastases were detected and effective surgical treatment depended upon the degree of spread in soft tissue. Inoperable tumours had infiltrated the pharyngeal and tonsillar area. Some resected cases survived for one year or more. PMID- 3110322 TI - Combined calcifying epithelial odontogenic tumor and adenomatoid odontogenic tumor. AB - A case of combined epithelial odontogenic tumor associated with an unerupted maxillary canine tooth is described. The relative proportion of adenomatoid odontogenic tumor tissue and calcifying epithelial odontogenic tumor areas in a given tumor in determining the behaviour and growth potential of this entity is discussed. PMID- 3110323 TI - Intramural calcifying epithelial odontogenic tumor. AB - The calcifying epithelial odontogenic tumor (CEOT) is a rare lesion of the jaws. It accounts for about 1% of all odontogenic tumors. The CEOT occurs primarily in the molar-premolar region of the mandible, and 52% of cases are associated with an unerupted tooth. This report describes an unusual case in a 37-year-old woman. The tumor arose in the molar area of the right mandible, appeared radiographically as a radiolucent lesion, and was thought to be a dentigerous cyst in association with an impacted first molar. The lesion was enucleated. Microscopic examination showed it to be a dental sac, within which were the 3 elements of a typical CEOT: squamoid cells with eosinophilic cytoplasm, the homogeneous eosinophilic substance, and calcium salt deposits in the form of Liesegang rings. PMID- 3110324 TI - Melanin-pigment in complex odontoma. AB - A case of complex odontoma, which contained melanin-pigment in the odontogenic epithelial cells in a 19-year-old Japanese male is reported. In addition to the characteristic histopathologic features of complex odontoma, odontogenic epithelial cells containing melanin-pigment were widely distributed in the fibrous connective tissue stroma which differed from that of the dental papilla in cellular appearance. No dendritic cells containing melanin-pigment were found in any sections. The possible histogenesis of melanin-pigment in the odontogenic epithelial cells was discussed, though no conclusion could be drawn from the present observation as to its origin in complex odontoma. PMID- 3110325 TI - Thalassemia diagnosed through facial distortion. AB - Thalassemia is an inherited genetic disorder of hemoglobin synthesis characterized by a reduction of either alpha or beta chains of globin. Typical features of patients with thalassemia are skeletal modifications, particularly in the skull and in the malar bone. This report describes a patient who was originally found to have an oro-facial deformity and subsequently demonstrated clinical and laboratory findings consistent with those recorded for thalassemia intermedia. PMID- 3110326 TI - Chondroid osteosarcoma of the maxilla. AB - A case of chondroid osteosarcoma of the maxilla is reported. This is itself a rare lesion but in this instance diagnosis was made more difficult for 2 reasons. On presentation, there was little radiological evidence of bone destruction and also, during follow-up and before biopsy-proven diagnosis, the lesion showed considerable evidence of repair on 2 occasions. PMID- 3110327 TI - Efficacy of a self-aspirating syringe. AB - Several self-aspirating syringes have been introduced into dentistry during the last decade. The efficacy of such a self-aspirating system, the EVERS-syringe, has been tested in relation to varying liquid pressure and diameter of the needle. It was found that the EVERS system was able to secure aspiration, irrespective of pressure and needle diameter. The passive back-flow of liquid through the needle, however, did depend on pressure and needle diameter. 3 different brands of local analgetics were evaluated, and it was found that the degree of self-aspiration was identical, regardless of brand and thereby cartridge type. PMID- 3110328 TI - Use of a pneumatic osteotome to simplify orthognathic surgery. PMID- 3110329 TI - Subrenal capsule assay applied to examine the sensitivity of allogenic mouse fibrosarcoma to hyperthermia, chemotherapeutic drugs or combined treatment. AB - The thermosensitivity and chemosensitivity of fibrosarcomas of C3H/He mouse were investigated using the subrenal capsule assay with female ICR mice as host. Five typical chemotherapeutic drugs (mitomycin C, adriamycin, 5-fluorouracil, cis DDplatinum and cyclophosphamide) tested were effective in suppressing tumour growth. Total-body hyperthermia given at 41.5 degrees C for 30 min twice during the 6-day period exerted little effect. However, an interactive effect was found with the combination of hyperthermia and mitomycin C. The combination of hyperthermia with other drugs failed to exhibit an interactive effect, since the effects of the drugs alone were considerable. The potential clinical applicability of this test is discussed. PMID- 3110331 TI - Use of the CH lymphomas as models of murine B cell differentiation. PMID- 3110332 TI - Establishment and morphologic characterization of a cell line (DMBA-OC-1) from 7,12-dimethylbenz(a)anthracene-induced rat ovarian carcinoma. AB - A new cell line (DMBA-OC-1) from 7,12-dimethylbenz (a) anthracene (DMBA) which induced ovarian carcinoma in rat was established and characterized. DMBA-OC-1 cells showed a paving-stone-like growth pattern at around the 10th to 20th passage, but at the point exceeding the 40th passage the cells showed a spindle form, having strong trends both towards flocculation and piling-up. Furthermore, diastase-resistant PAS-positive and hyaluronidase-digested Alcian blue positive substances were observed in cytoplasms. The cells also showed marked phagocytic activity. These findings suggest that DMBA-OC-1 cells are most likely the site of mesothelial cell origin. PMID- 3110333 TI - [Genetic studies on the ossification of the posterior longitudinal ligament]. AB - The genetic mechanism of OPLL (ossification of the posterior longitudinal ligament) was investigated through a family study including 62 probands and 129 relatives using X-ray examination of the spine. The study showed that the prevalence of OPLL was 29.1% in men and 25.7% in women with a tendency of increase with age. As the mode of inheritance, the segregation ratio or children of probands was that of simple recessive; the segregation ratio of siblings was either simple recessive or dominant. The recurrence rate of siblings excluded polygenes; this mode of transmission and the penetrance suggested that the most probable mode of inheritance of OPLL would be simple dominant. As genetic markers, various blood groups, serum groups, and erythrocyte isozyme groups were examined in 23 patients with OPLL. Gc serum groups and EsD isozyme groups displayed some association with OPLL in comparison with the normal controls. PMID- 3110330 TI - Surface antigens associated with human B cell activation. PMID- 3110334 TI - Endogenous luteinizing hormone release using human menopausal gonadotropins for in vitro fertilization. AB - This study demonstrates that luteinizing hormone (LH) release may occur despite sustained elevations of estradiol E2 in women receiving human menopausal gonadotropin. Mean levels of E2 did not correlate with the LH surge, however, the follicle number and a rapid rise in E2 did. Therefore, it appears that the protective influence of inhibitory proteins secreted by multiple follicles can be overridden, allowing spontaneous LH release. PMID- 3110336 TI - Early observations on the lupus anticoagulant. PMID- 3110335 TI - Ovarian carcinoma in a patient hyperstimulated by gonadotropin therapy for in vitro fertilization: a case report. PMID- 3110338 TI - Cancer induced anti-inflammation and its potentiation by tumor excision and rechallenge. AB - Tumor rechallenge following primary tumor excision elicits systemic anti inflammation that occurs rapidly, affects granulocytes as well as macrophages and is more severe, longer in duration, and induced by fewer tumor cells than the macrophage specific anti-inflammatory effect sometimes seen after primary tumor challenge. Factors important in the pathogenesis of this abnormality are the following. First, primary tumor excision was required as defects did not occur when a second tumor was transplanted during primary tumor growth. Second, the abnormality was restricted to neoplastic cells since normal cells were unable to substitute for either primary or secondary tumor challenge. Third, the anti inflammatory effect was not due to surgical trauma or local irritation. Fourth, defective inflammation occurred in syngeneic but not allogeneic rats, suggesting an immunological basis for the anti-inflammation. Fifth, elevated glucocorticoids, such as might be expected from an immunological reaction or release of IL-1, may be a contributing but not sole cause for the phenomenon. PMID- 3110337 TI - Regulation of human large granular lymphocyte and T cell growth and function by recombinant interleukin 2: induction of interleukin 2 receptor and promotion of growth of cells with enhanced cytotoxicity. AB - Human large granular lymphocytes (LGL), which account for virtually all natural killer activity, and T cells were separated from low and high density fractions of Percoll gradients, respectively. We were unable to detect interleukin 2 receptors (IL 2R) on fresh LGL and T cells using flow cytometric analysis with anti-Tac monoclonal antibody or radiolabeled probes with [125I]anti-Tac. IL 2R messenger ribonucleic acid was not observed in fresh LGL or T cells. Although phytohemagglutinin induced the expression of IL 2R on purified LGL and T cells, recombinant IL 2 (rIL 2) alone induced IL 2R messenger ribonucleic acid, IL 2R, and proliferation of LGL but not of T cells. The high level of cytotoxicity of cultured LGL against K562 cells was directly dependent on rIL 2. When T cells were costimulated by phytohemagglutinin and rIL 2 for 3 days, only very low levels of cytotoxicity were generated. Proliferation and cytotoxicity against K562 cells inhibited the culture of LGL in the presence of anti-Tac antibody for 3 days. LGL began to grow more rapidly after 5 days in culture with rIL 2 alone. When rIL 2 were removed from growing LGL for 1 day, proliferation completely stopped, and cytotoxicity was no longer detected. These data indicate that rIL 2 induces IL 2R expression in fresh LGL at the transcriptional level, promoting growth and enhancing cytotoxicity. More importantly, the presence of rIL 2 is necessary and sufficient to induce proliferation of resting LGL and to maintain the growth of LGL with potent lytic activity. PMID- 3110339 TI - Transport and metabolism of extracellular free fatty acids in adipose tissue of fed and fasted mice. AB - We used a new tracer technique, direct tracer injection of [1-14C]palmitate-serum albumin into extracellular fluid (ECF) of epididymal fat pads, to study relative transport rates of ECF-free fatty acids (FFA) to cell-FFA and subsequent esterification to diglyceride fatty acid (DGFA) and triglyceride fatty acid (TGFA) in adipose tissue versus movement of ECF- and cell-FFA into the circulation of mice fed ad libitum or fasted 48 hr. Radioactivity was measured in the following fractions at varying times (for 1 hr): ECF-FFA, cell-FFA, cell DGFA, cell-TGFA, plasma-FFA (total lipids), and breath CO2. Pool sizes of ECF FFA, cell-FFA, cell-TGFA, and plasma-FFA were determined. Analysis by multicompartmental methods (SAAM) indicates that the ECF-FFA compartment of epididymal fat pads is in a relatively rapid exchange with a cellular-FFA compartment, but neither is in direct, nor appreciably rapid, communication with circulating FFA. FFA is rapidly esterified in adipocytes of fed mice, but esterification is significantly inhibited in mice fasted for 48 hr. In both dietary states, essentially all labeled FFA appearing in the circulation was derived from ECF-FFA that were first transferred to the cell, esterified to TGFA, then hydrolyzed to FFA before being transported to the circulation. PMID- 3110340 TI - Prospective payment: DRGs and ethics. PMID- 3110341 TI - Ethical issues in the use of a prospective payment system: the issue of a severity of illness adjustment. AB - The current Medicare prospective payment system has many positive incentives for hospitals to control costs. Hospitals are increasing outpatient surgery, decreasing admissions, decreasing length of stay, and decreasing use of ancillary services. These are just the effects that Congress and the Health Care Financing Administration hoped for to save the Medicare trust fund. However, there has been evidence of some adverse outcomes including premature discharge, "dumping" sicker patients and patients without insurance, and adverse impact on hospitals with specialty centers. We examine these issues and present a possible solution based on a new Computerized Severity Index. PMID- 3110342 TI - DRGs and the idea of a just price. AB - Ostensibly, the DRG prospective payment system represents a modern effort to legislate an enforceable system of just prices. As a practical matter, however, justice is conflated with mere familiarity, and the real goal of DRGs has always been cost containment. Abstract and concrete discussions of the computation of DRG payment schedules illustrate their actual operation. PMID- 3110343 TI - DRGs: justice and the invisible rationing of health care resources. AB - Are DRGs just? This is the primary question which this essay will answer. But there is a prior methodological question that also needs to be addressed: How do we go about rationally (non-arbitrarily) assessing whether DRGs are just or not? I would suggest that grand, ideal theories of justice (Rawls, Nozick) have only very limited utility for answering this question. What we really need is a theory of "interstitial justice," that is, an approach to making justice judgments that is suitable to assessing the social practices and institutions that comprise the interstices of our social life as opposed to its basic structure. Rawls's appeal to "our considered moral judgments" provides us with a useful starting point for this task, which we shall discuss in the first part of this essay. In the second part, we shall actually assess DRGs from the perspective of interstitial justice. What we shall show is that DRGs violate a large number of our considered judgments regarding a just approach to financing health care for the elderly in a cost-effective manner. This is true to such an extent that efforts to reform DRGs and make them fairer, such as the recent effort by Robert Veatch, should be abandoned. In the concluding section of the essay we discuss one especially pernicious feature of DRGs, namely, that they represent an invisible approach to rationing access to health care. In the minds of many this is one of the virtues of DRGs. That claim needs critical examination. PMID- 3110344 TI - A type I diabetic patient who experienced three occasions of ICSA associated exacerbations and remissions of diabetes mellitus. PMID- 3110345 TI - Effects of aldose reductase inhibitor on the peripheral nerve function during ischemia in diabetics. PMID- 3110346 TI - Remission in non-insulin dependent diabetes. PMID- 3110347 TI - Regulation of human eosinophil viability, density, and function by granulocyte/macrophage colony-stimulating factor in the presence of 3T3 fibroblasts. AB - Normodense human peripheral blood eosinophils were isolated under sterile conditions from the 22/23 and 23/24% interfaces and the cell pellet of metrizamide gradients. After culture for 7 d in RPMI media in the presence of 50 pM biosynthetic (recombinant) human granulocyte/macrophage colony-stimulating factor (rH GM-CSF), 43 +/- 7% (mean +/- SEM, n = 8) of the cells were viable; in the absence of rH GM-CSF, no eosinophils survived. The rH GM-CSF-mediated viability was concentration dependent; increased survival began at a concentration of 1 pM, a 50% maximal response was attained at approximately 3 pM, and a maximal effect was reached at concentrations of greater than or equal to 10 pM rH GM-CSF. In the presence of rH GM-CSF and mouse 3T3 fibroblasts, 67 +/- 6% (mean +/- SEM, n = 8) of the eosinophils survived for 7 d. In a comparative analysis, there was no difference in eosinophil viability after 7 and 14 d (n = 3) in the presence of 50 pM GM-CSF and fibroblasts. Culture with fibroblasts alone did not support eosinophil survival. The addition of fibroblast-conditioned media to rH GM-CSF did not further improve eosinophil viability, indicating a primary role for GM-CSF in supporting these eosinophil cell suspensions ex vivo and a supplementary role for 3T3 fibroblasts. Eosinophils cultured for 7 d localized on density gradient sedimentation at the medium/18, 18/20, and 20/21 interfaces of metrizamide gradients, indicating a change to the hypodense phenotype from their original normodense condition. In addition, the cultured eosinophils generated approximately 2.5-fold more LTC4 than freshly isolated cells when stimulated with the calcium ionophore A23187 and manifested sevenfold greater antibody-dependent killing of S. mansoni larvae than the freshly isolated, normodense cells from the same donor. Thus we demonstrate the rH GM-CSF dependent conversion in vitro of normodense human eosinophils to hypodense cells possessing the augmented biochemical and biological properties characteristic of the hypodense eosinophils associated with a variety of hypereosinophilic syndromes. In addition, these studies provide a culture model of at least 14 d suitable for the further characterization of hypodense eosinophils. PMID- 3110348 TI - Genotypic analysis of B cell colonies by in situ hybridization. Stoichiometric expression of three VH families in adult C57BL/6 and BALB/c mice. AB - The filter paper disc method for cloning inducible lymphocytes was used to census the splenic B cell population of C57BL/6 and BALB/c mice for the expression of three VH gene-families, VH X-24, -Q52, and -J558. B cell colonies, arising from single founder lymphocytes, were identified by in situ hybridization with VH family- and C mu-specific cDNA probes. Some 6.7 X 10(4) C mu+ colonies were screened. Among C57BL/6- or BALB/c-derived colonies, approximately 3% were VH X 24+, approximately 19% were VH Q52+, and approximately 54% were VH J558+. These frequencies are consistent with a process of equiprobable expression for individual VH segments, and provide direct evidence that normal splenic B lymphocytes use a process of random genetic combinatorics to generate the antibody repertoire. PMID- 3110349 TI - A new variable region in mouse immunoglobulin lambda light chains. AB - A series of lambda+ murine hybridomas were derived from a BALB/c mouse after a single injection of anti-lambda 2 antibodies coupled to LPS. Nine lambda B cell clones (five lambda 2 and four lambda 3) were expected and seven reacted with antibodies specific for the C lambda 2 constant region but showed a particular isoelectric spectrum. Their RNA products did not hybridize with the V lambda probe. The partial DNA sequence of gene segments coding the unexpected light chain of one hybridoma shows that the V gene segment has only 55% homology with the V lambda 2 gene segment sequence and that J lambda 2 and probably C lambda 2 gene segments are used. Taken together, these results demonstrate the existence of a new lambda light chain. PMID- 3110350 TI - Characterization of CD3+, CD4-, CD8- clones expressing the putative T cell receptor gamma gene product. Analysis of the activation pathways leading to interleukin 2 production and triggering of the lytic machinery. AB - Four clones were derived from human peripheral blood T lymphocytes from which CD4+ and CD8+ cells had been removed by treatment with specific mAbs and complement. All expressed the CD2+, 3+, 4-, 8-, T44- phenotype, and did not react with the WT31 mAb, which is specific for a framework determinant of the CD3 associated alpha/beta heterodimer which serves as receptor for antigen on most human T lymphocytes. Surface iodination followed by crosslinking with dithiobis succinimidyl propionate (DSP) and immunoprecipitation with anti-CD3 mAbs indicated that, in all four clones, the CD3-associated molecules consisted of a major 45 kD band and a minor band of 43 kD. Northern blot analysis showed that mRNA for the gamma chain was expressed at high levels, whereas mRNA for the alpha chain was missing; beta chain mRNA was present in a defective form (1 kb instead of 1.3 kb). These data support the concept that these clones may express, in association with CD3, the molecular product of the T cell receptor gamma genes instead of the typical alpha/beta heterodimer. CD3+, WT31- clones lysed the NK sensitive K562 target cells and produced IL-2 upon stimulation with PHA. In addition, they released IL-2 after triggering with soluble anti-CD3 mAbs or with an appropriate combination of anti-CD2 mAbs (in the presence of adherent cells). When CD3+, WT31- clones were incubated with an anti-CD3 producing hybridoma as triggering target, the latter was efficiently lysed. Target cell lysis also occurred when a suitable combination of anti-CD2 mAbs-producing hybridomas was used. Therefore, CD3+, WT31- cells appear to use two pathways of cell activation that function also in conventional CD3+, WT31+ T cells, but they lack a third putative pathway initiated by T44 surface molecules. PMID- 3110351 TI - Emergence of immunoglobulin variants following treatment of a B cell leukemia with an immunotoxin composed of antiidiotypic antibody and saporin. AB - The potency and specificity of immunotoxins consisting of monoclonal antiidiotype conjugated to the ribosome-inactivating protein, saporin, have been evaluated in the treatment of guinea pig L2C B lymphocytic leukemia. The immunotoxins were therapeutically much more effective than their parent antibodies. Their specificity reflected that of their antiidiotype component. Although the leukemia emerged eventually in most animals treated with these conjugates, most of the cells showed altered Ig expression, which rendered them resistant to the therapy. Commonly, the emerging cells had lost mu heavy chain production, leaving them negative for intracellular, surface, and secreted IgM, but still positive for lambda light chain production. In addition, a minor group of L2C variants was identified in a protocol designed to detect mutants at very low frequency: here the cells were exposed in vitro to immunotoxin and, while still viable as judged by dye-exclusion, inoculated in large numbers into animals. In tumor that emerged under these circumstances, the majority of cells were again immunoglobulin negative; however a minority exhibited IgM with an altered idiotype (Idiotope loss variants), rendering them unreactive with immunotoxin. Immunotherapy with unmodified anti-Id antibody alone does not reveal these variants, and we suggest it is the increased selective force exerted by the highly potent immunotoxins that allow these minor nonreactive populations to emerge. PMID- 3110352 TI - Transmembrane signaling of interleukin 2 receptor. Conformation and function of human interleukin 2 receptor (p55)/insulin receptor chimeric molecules. AB - Chimeric genes were constructed which gave rise to the expression of novel receptor molecules consisting of the extracellular domain of the human interleukin 2 receptor (IL-2-R; p55 or Tac antigen) joined to the transmembrane domain and either full-length or truncated cytoplasmic domain of the human insulin receptor (Ins-R). Expression studies using mouse T cell line EL-4 revealed that the chimeric receptors are able to manifest properties indistinguishable from the authentic IL-2-R. On the other hand, stimulation of the tyrosine kinase activity by IL-2 was not observed in the chimeric receptor with the entire cytoplasmic domain of the Ins-R. These findings thus shed light on the structural conformation and functioning of the IL-2-R complex. PMID- 3110353 TI - T suppressor cell growth factor and anti-CD3 antibodies stimulate reciprocal subsets of T lymphocytes. AB - Because of the central role of IL-2 in clonal expansion of T cells, we have postulated that lymphocyte subpopulations with opposing regulatory functions might be independently regulated by differential requirements for expression of cell-surface IL-2-R. Purified CD4+ and CD8+ cells proliferated in an IL-2 dependent manner to crosslinked anti-T cell receptor antibodies (anti-CD3-Seph). Similarly, both CD4+ and CD8+ cells became IL-2 responsive after incubation in T suppressor cell growth factor (TsGF), a newly described approximately 8,000 Mr product of activated CD4+ cells. In support of our hypothesis, however, we observed that subpopulations of CD4+ and CD8+ cells, possessing distinct cell surface antigens, showed differential responses to these stimuli. Those cells of suppressor-inducer or suppressor-effector phenotype failed to proliferate when cultured in anti-CD3-Seph plus IL-2, but did proliferate in an IL-2-dependent manner to TsGF. Furthermore, the suppressor-effector population was unresponsive to TsGF plus IL-2 when cocultured in anti-CD3-Seph, suggesting that functionally induced Ts may be refractory to growth stimuli. Conversely, cells with helper inducer or cytolytic phenotype proliferated when incubated in anti-CD3-Seph and IL-2, while remaining essentially unresponsive to TsGF and IL-2. The results could not be explained by differences in the level of CD3 expression by the T cell subsets. Thus, cells within the helper and suppressor lineages appear to have distinct and reciprocal patterns for the induction of IL-2 responsiveness. PMID- 3110354 TI - Inhibition of cytokine production by cyclosporin A and transforming growth factor beta. AB - We investigated the ability of cyclosporin A (CsA) and transforming growth factor beta (TGF-beta) to modulate the production of TNF-alpha and TNF-beta and IFN gamma by unseparated, nonadherent, and adherent PBMC. Treatment of unseparated PBMC with CsA resulted in a significant dose-dependent inhibition of all three cytokines ranging from greater than 90% inhibition for IFN-gamma and TNF-beta, to approximately 70% for TNF-alpha. Pretreatment of unseparated or nonadherent PBMC with TGF-beta inhibited the production of IFN-gamma by 60-70%. However, the inhibition of TNF-alpha and TNF-beta production by these cells was only minimally affected, and at 0.1-1 ng/ml TGF-beta could enhance TNF-alpha production by unseparated PBMC. In contrast, pretreatment of adherent PBMC with TGF-beta inhibited the production of TNF-alpha by approximately 60%. TGF-beta also inhibited both TNF-alpha production and tumor cell cytotoxicity mediated by murine peritoneal-derived macrophages. These observations indicate that the biological effects of CsA and TGF-beta on immune functions are of a wider range than previously reported. PMID- 3110355 TI - Interferon gamma and lymphotoxin or tumor necrosis factor act synergistically to induce macrophage killing of tumor cells and schistosomula of Schistosoma mansoni. AB - Macrophages play a crucial role in the defense against tumors and parasites. Activation of tumoricidal and microbicidal effector mechanisms requires stimulation of macrophages with macrophage-activating factors (MAF). One such MAF is interferon gamma (IFN-gamma). In some assays, substantial activity of IFN gamma on murine macrophages, however, is only observed in synergy with lipopolysaccharide (LPS) or other cytokines (1). In addition, certain cytokines have been shown to induce monocyte or macrophage activation in the absence of IFN gamma (2-5). We previously described lymphokines in the supernatant of a murine T cell clone that synergized with IFN-gamma in the induction of tumoricidal and schistosomulicidal murine macrophages (1). We called this lymphokine(s) macrophage cytotoxicityinducing factor 2 (MCIF2)(1). A candidate for MCIF2 was lymphotoxin (LT), because the T cell clone supernatant contained high amounts of LT. LT is functionally homologous and structurally related to the macrophage product tumor necrosis factor (TNF). Therefore, we tested whether recombinant (r) LT or rTNF can function as MAF. We report here that rLT or rTNF synergize with rIFN-gamma in the induction of tumoricidal and schistosomulicidal murine macrophages. PMID- 3110356 TI - Independent association of T cell receptor beta and gamma chains with CD3 in the same cell. AB - We have demonstrated that the PEER cell line, which expresses a CD3-associated TCR gamma chain on the cell surface, synthesizes TCR beta chain intracellularly. A percentage of this TCR beta chain associates with the CD3 complex intracellularly. These results indicate that TCR beta and gamma chains can be synthesized by one cell line, and that these chains can independently associate with the CD3 complex. However, the results argue against the formation of TCR beta gamma chain complexes in this cell line. PMID- 3110357 TI - Selective use of the VHQ52 family in functional VH to DJH rearrangements in a B precursor cell line. AB - AT11-2, an Abelson virus-transformed cell line has DJH complexes on both chromosomes and is able to form functional variable region genes by the joins of VH genes to the DJH complexes during culture. Therefore we examined which VH gene family was used in functional VH to DJH recombinations in AT11-2. Surprisingly, of 32 independent functional VH to DJH recombinational events in AT11-2, 31 events used the VH segments of the VHQ52 family, and the remaining one used the VH segment of the VH7183 family. Thus, we describe here the first B precursor cell line that almost selectively uses the VHQ52 family in functional VH to DJH rearrangements. The selective use of the VHQ52 family in this B precursor cell line strongly indicates nonrandom use of VH gene families, and the existence of a stage at which the VHQ52 family is preferentially used during the normal development of early pre-B cells and has important implications for understanding the ontogeny of VH repertoire development. Furthermore, this cell line should prove extremely valuable in further studies of this kind. PMID- 3110358 TI - Species heterogeneity in macrophage expression of the CD4 antigen. AB - The CD4 antigen is expressed on T cells of all mammalian species examined and appears to play an important role in the response of T cells to antigen. In humans, the molecule acts as a receptor for the AIDS virus. Previous studies have demonstrated that M phi in the rat and human also express the CD4 antigen, which is indistinguishable from that on T cells. In this paper we demonstrate by FACS analysis, Northern blot hybridization, and immunoperoxidase labeling that, in striking contrast to the rat and human, mouse M phi do not express the CD4 (L3T4) antigen. This species heterogeneity indicates that T cells and M phi regulate CD4 antigen expression independently and that CD4 may not be essential for M phi function. PMID- 3110359 TI - Antibody-induced modulation of the CD3/T cell receptor complex causes T cell refractoriness by inhibiting the early metabolic steps involved in T cell activation. AB - We investigated the mechanism involved in T cell unresponsiveness that follows the monoclonal antibody-induced surface modulation of the CD3-TCR complex. We determined whether modulation of CD3-TCR affected the early metabolic steps such as [Ca2+]i rise and InsP3 formation. A strong inhibition of the increase on [Ca2+]i mediated by either anti-TCR or anti-CD2 mAbs was detected. In contrast, surface modulation of CD2 molecules did not prevent the [Ca2+]i increase induced by anti-TCR mAb. Similarly, InsP3 increase was strongly reduced only after modulation of CD3-TCR complex (but not of CD2 molecules). Therefore, it appears that surface modulation of CD3-TCR complex causes T cell refractoriness by inhibiting the very early metabolic events that follow receptor-ligand interactions. PMID- 3110360 TI - Air space: the embryonic medium. AB - Normalization of gas exchange and growth of chicken embryos incubated under abnormal conditions with regard to eggshell conductance and barometric pressure is directed to restoring the normal water loss from the eggs and the normal pattern of air space gas tensions during development. The latter is achieved by maintaining an O2 tension of 149 torr in the gas mixture supplied to the incubator and by reducing the incubator ventilation rate to compensate for increased, standard or effective, eggshell conductances. Thus, for maintenance of normal air space gas tensions, a decrease of the diffusive resistance of an egg requires a similar increase of the convective resistance so that the total resistance against gas transport remains normal. The latter must be set at a value given by (149-PA)/M, where PA is the normal air space O2 tension, torr, and M is the normal O2 uptake, ml(STPD)/day. This value is independent of embryonic age, because PA is directly proportional to M during development. Thus the convective resistance required for maintenance of normal PA and M values is given by the difference between (149-PA)/M and the diffusive resistance. Such PA and M values can be maintained in eggs with the minimum diffusive conductance, M/(149 PA), thus requiring an infinite convective conductance, to infinite diffusive conductance, which requires a minimum convective conductance, M/(149-PA). This minimum is predicted for all shell-less eggs, viz., for the continuous replacement of diffusive by convective gas transport. PMID- 3110361 TI - Functional properties of primitive and definitive red cells from chick embryo: oxygen-binding characteristics, pH and membrane potential, and response to hypoxia. AB - We compare properties of primitive and definitive red cells in three areas effect of different hemoglobin patterns on oxygen affinity cellular response to hypoxia, and red cell membrane potential and cell pH since during incubation blood pH decreases by 0.5 pH. We find that the first population of definitive red cells has many properties in common with the preceding primitive red cells. The oxygen binding curves are nearly identical despite the fact that the definitive red cells contain only the adult hemoglobins A and D; in particular, n values greater than 4 are recorded in the upper saturation range. Within the definitive red cell population there is a drastic increase in the oxygen affinity between days 7 to 14. Hypoxia causes a series of coordinated changes in definitive but not primitive red cells, involving the phosphate pattern (2,3 DPG, ATP) as well as changes of carbonic anhydrase activity and oxygen affinity. The results suggest that the oxygen pressure controls part of the differentiation program of the definitive cell population and that control is dependent on plasma factors of high molecular weight. The membrane potential of primitive and early definitive red cells is a proton diffusion potential. During development proton conductivity decreases, and at day 16 proton and chloride distribution can be adequately described by the Donnan equilibrium. The linkage between membrane potential and proton distribution allows maintenance of red cell pH at about 7.2, irrespective of external pH, which greatly facilitates the adjustment of embryonic oxygen affinity. PMID- 3110362 TI - Cultivation of the early quail embryo: induction of embryogenesis under in vitro conditions. AB - Embryogenesis of the quail can be induced under in vitro conditions by avoiding drying out of the germinal area. This is attained either by covering the surface of the egg content with diluted albumen or by regulating the water loss in the incubating system by means of a membrane. PMID- 3110364 TI - Altitude hypocapnia at 2,800 m does not affect development of the chicken embryo. AB - Eggs laid at sea level and incubated at high altitude are subject to hypoxia, hypocapnia, and excessive water loss, resulting in retarded development and poor hatchability. The effect of altitude hypocapnia alone was studied in two series of eggs incubated at a simulated altitude of 2,800 m, PB = 542 torr; the incubator was ventilated at a low flow rate with O2-enriched air; the relative humidity was 70-74%, PH2O 34.4-36.4 torr; ambient PO2 about 130 torr at the plateau stage. In the normocapnic series, CO2 produced by the embryos increased ambient PCO2 to 14 torr at 18-19 days; altitude hypoxia, hypocapnia, and excessive water loss were practically compensated for. In the hypocapnic series, ambient CO2 was almost completely absorbed by soda lime, so that only hypocapnia was not compensated for. In 17-19-day eggs with similar sea level mass specific shell conductances [sp GH2O = 0.26-0.25 mg [g.d.torr]-1], the measured PO2 in the gas space, hematocrit, hemoglobin concentration, lengths of beak and third toe, and masses of body and brain were essentially the same in both series. The masses of heart, liver, and left wing were slightly different on day 19. Altitude hypocapnia alone, without altitude hypoxia and excessive water loss, had almost no significant effect on the embryos' development and hatchability. PMID- 3110363 TI - Modulation of growth and metabolism of the chick embryo by a brief (72-hr) change in oxygen availability. AB - Growth of the chick embryo is accelerated by brief (72-hr) exposure to 60% O2 beginning on day 16 of incubation, and acute (2-3 hr) hyperoxia stimulates oxygen consumption (VO2). However, the increment in VO2 that accompanies acute exposure to 60% O2 is only about half that required to account for the degree of growth acceleration observed during 72 hr of hyperoxia. We tested the hypothesis that the magnitude of the oxygen-induced change in embryonic metabolism depends on the length of exposure by making daily measurements of embryonic VO2 during brief (72 hr) exposure to 60% or 15% O2. White leghorn eggs were incubated in 21% O2 for 15 days. On day 16 the experimental eggs were switched to 60% or 15% O2; control eggs were maintained in 21% O2. Oxygen consumption and CO2 production (VCO2) were measured daily. Embryo and organ weights were compared on day 18. Wet and dry weights of briefly hyperoxic embryos were significantly greater than those of normoxic controls. The relative increase in wet weight was significant for the heart and liver but not the brain. Oxygen consumption increased 7% relative to control after 24 hr of hyperoxia and 17% after 72 hr; VO2/gm embryo was 9% greater than control on day 18. Normal growth deceleration was exaggerated by hypoxia; mean wet and dry weights of the briefly hypoxic embryos were significantly less than those of controls. Organ wet weights also showed growth retardation, although the relative decrease in brain weight was not significant. Body water concentration increased in briefly hypoxic embryos. Oxygen consumption was 13% less than control after 24 hr and 17% less after 72 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110365 TI - Invertebrate red blood cell carbonic anhydrase. AB - This is the first report documenting the presence of carbonic anhydrase (CA) for any invertebrate red cells. CA activity was measured in plasma, hemolysates of blood cells, and in hemolymph of selected species of invertebrates. Annelid red blood cells (RBC) and sipunculid pink blood cells both possessed significant levels of CA activity. Molluscan RBC, on the other hand, lacked CA activity. The distribution appears to have fallen along phylogenetic lines, with CA being present only in blood cells of the two more closely related groups. However, the presence of extracellular CA was confirmed in oyster hemolymph. Oyster hemolymph CA showed a similar affinity (Ki) for the sulfonamide inhibitors acetazolamide and ethoxzolamide, as did the vertebrate RBC CA II isozyme, supporting the idea that this isozyme could be the ancestral form of the enzyme. PMID- 3110366 TI - Cost-effective drug testing. PMID- 3110367 TI - Prostaglandins: fundamental and clinical aspects. PMID- 3110368 TI - Bacteremia in childhood acute leukemia. PMID- 3110369 TI - Force: velocity relationship in single isolated toad stomach smooth muscle cells. AB - The relationship between force and shortening velocity (F:V) in muscle is believed to reflect both the mechanics of the myosin cross-bridge and the kinetics of its interaction with actin. To date, the F:V for smooth muscle cells has been inferred from F:V data obtained in multicellular tissue preparations. Therefore, to determine F:V in an intact single smooth muscle cell, cells were isolated from the toad (Bufo marinus) stomach muscularis and attached to a force transducer and length displacement device. Cells were electrically stimulated at 20 degrees C and generated 143 mN/mm2 of active force per muscle cross-sectional area. At the peak of contraction, cells were subjected to sudden changes in force (dF = 0.10-0.90 Fmax) and then maintained at the new force level. The force change resulted in a length response in which the cell length (Lcell) rapidly decreased during the force step and then decreased monotonically with a time constant between 75 and 600 ms. The initial length change that coincided with the force step was analyzed and an active cellular compliance of 1.9% cell length was estimated. The maintained force and resultant shortening velocity (V) were fitted to the Hill hyperbola with constants a/Fmax of 0.268 and b of 0.163 Lcell/s. Vmax was also determined by a procedure in which the cell length was slackened and the time of unloaded shortening was recorded (slack test). From the slack test, Vmax was estimated as 0.583 Lcell/s, in agreement with the F:V data. The F:V data were analyzed within the framework of the Huxley model (Huxley. 1957. Progress in Biophysics and Biophysical Chemistry. 7:255-318) for contraction and interpreted to indicate that in smooth muscle, as compared with fast striated muscle, there may exist a greater percentage of attached force-generating cross-bridges. PMID- 3110370 TI - Temporary and permanent modifications to a single strain of mouse scrapie on transmission to rats and hamsters. AB - The interspecies transmission of scrapie is frequently associated with exceptionally long incubation periods at first passage in the new host compared to later passages (the species barrier effect). The basis of this was investigated using the 139A strain of scrapie which had been cloned by three serial passages in mice at limiting infectious doses. Cloned scrapie was passaged through hamsters (twice) or rats (thrice) and then reisolated in mice. Large species barrier effects were encountered on mouse-to-hamster and hamster-to-mouse passage resulting in the isolation of a mutant strain, 139-H/M, with properties very different from 139A. In contrast, the strain reisolated from rats was indistinguishable from 139A. However, a large species barrier was encountered at the mouse-to-rat passage but not at the rat-to-mouse passage. It is suggested that the transmission of scrapie between species may be associated with no change in properties or a permanent change in the scrapie genome due to the selection of mutants. A third possibility, the donor species effect, is a temporary change occurring only at first passage in the new host species which is largely or entirely caused by the introduction of material from the previous host. We speculate that the donor species effect could be explained if some host protein forms a functional part of the infectious agent. PMID- 3110371 TI - Synapsin I is associated with cholinergic nerve terminals in the electric organs of Torpedo, Electrophorus, and Malapterurus and copurifies with Torpedo synaptic vesicles. AB - Using an affinity-purified monospecific polyclonal antibody against bovine brain synapsin I, the distribution of antigenically related proteins was investigated in the electric organs of the three strongly electric fish Torpedo marmorata, Electrophorus electricus, Malapterurus electricus and in the rat diaphragm. On application of indirect fluorescein isothiocyanate-immunofluorescence and using alpha-bungarotoxin for identification of synaptic sites, intense and very selective staining of nerve terminals was found in all of these tissues. Immunotransfer blots of tissue homogenates revealed specific bands whose molecular weights are similar to those of synapsin Ia and synapsin Ib. Moreover, synapsin I-like proteins are still attached to the synaptic vesicles that were isolated in isotonic glycine solution from Torpedo electric organ by density gradient centrifugation and chromatography on Sephacryl-1000. Our results suggest that synapsin I-like proteins are also associated with cholinergic synaptic vesicles of electric organs and that the electric organ may be an ideal source for studying further the functional and molecular properties of synapsin. PMID- 3110372 TI - Noninvasive demonstration of in vivo 3-fluoro-3-deoxy-D-glucose metabolism in rat brain by 19F nuclear magnetic resonance spectroscopy: suitable probe for monitoring cerebral aldose reductase activities. AB - The metabolism of 3-fluoro-3-deoxy-D-glucose (3-FDG) in rat brain in vivo was investigated noninvasively using 19F nuclear magnetic resonance (NMR) spectroscopy. Following an intravenous infusion of 3-FDG, 400 mg/kg, four resonances assigned to the alpha and beta anomers of 3-FDG, 3-fluoro-3-deoxy-D sorbitol, and 3-fluoro-3-deoxy-D-fructose were clearly resolved in brain, a result indicating that 3-FDG is metabolized primarily into the aldose reductase sorbitol (ARS) pathway. An orally administered aldose reductase inhibitor, sorbinil, caused reduction of the flux of 3-FDG into the ARS, an observation suggesting that the method can be applied in quantitative studies of ARS pathway activities. Studies of 24-h urine specimens showed that in addition to the two metabolites observed in brain, F- was excreted into the urine. 3-FDG appears to be a suitable metabolic probe for assessing glucose metabolism in the ARS pathway by in vivo 19F NMR spectroscopy. PMID- 3110374 TI - Monoclonal antibodies against glutaraldehyde-conjugated dopamine. AB - Four mice were immunized with dopamine (DA)-glutaraldehyde (G)--protein conjugates over a period of 8-10 weeks. Polyclonal antisera, obtained at various intervals, were tested using an enzyme-linked immunosorbent assay (ELISA). All had anti-conjugated DA antibodies. As soon as good antibody affinity was detected between 10(-10) and 10(-6) M, the mouse yielding the highest apparent affinity was killed, and the spleen was dissected out. Hybridomas were obtained from spleen cells fused with SP2/O/Ag myeloma cells. Supernatant culture media of hybridomas were tested for the presence of anti-conjugated DA antibodies with the ELISA method. Selected hybridomas giving good antibody affinity and specificity were then cloned by the limiting dilution technique. The resulting supernatant culture media were again tested by ELISA. Clones that gave a high antibody affinity (10(-10)-10(-8)M) for G-conjugated DA were used for histochemical localization of DA in rat brain. G-fixed rat brains were sectioned from the telencephalon to the mesencephalon, reduced with sodium borohydride, and prepared for peroxidase-antiperoxidase immunocytochemistry using supernatant (diluted 1:100) or ascites fluid (diluted 1:50,000). Dense networks of very fine fibers were observed in the striatum, septum, and cortex. Numerous immunoreactive cell bodies were found in the ventral tegmental area, the substantia nigra, the hypothalamus, and the dorsal raphe. The ELISA tests and adsorption controls suggested that the monoclonal antibody allowed highly specific detection of DA in tissues. PMID- 3110373 TI - Alkylation of free sulfhydryls fortifies electroplax subsynaptic structures. AB - The cysteine-rich 43,000-dalton peripheral membrane protein, nu 1, is localized at the cytoplasmic face of electroplax and muscle cholinergic synapses, where it is thought to play an important role in the endplate supramolecular structure. The peripheral membrane protein properties of nu 1 are inferred by its removal from nicotinic cholinergic membranes by the action of mild alkali or lithium diiodosalicylate. An interesting property of nu 1 is its high concentration of free sulfhydryl groups, whose exact role in synaptic structure is still largely unknown. Alkylation of free sulfhydryls with N-ethylmaleimide (3 mM) has a profound effect on the association of nu 1 with synaptic membranes, rendering nu 1 unextractable by pH 11 treatment or by lithium diiodosalicylate and, concomitantly, decreasing nu 1's electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels. Iodoacetamide and iodoacetate have similar effects, but at concentrations 10- to 100-fold higher than required for N-ethylmaleimide. Furthermore, sulfhydryl modification also stabilizes the association of nicotinic receptor subunits with the detergent-insoluble cytoskeleton. N-Ethylmaleimide treatment increases the fraction of insoluble receptor molecules on extraction with Triton X-100, sodium cholate, or octylglucoside. These results suggest an important role of sulfhydryl groups in the structural stability of the postsynaptic cholinergic membrane. PMID- 3110376 TI - A direct bioautographic tlc assay for compounds possessing antibacterial activity. AB - A simple bioassay for the direct detection of antibacterial compounds on tlc plates has been developed. A series of natural products and different stationary phases were tested in order to establish the utility of the assay for the isolation of antibacterial compounds from higher plants. PMID- 3110375 TI - Turnover of brain monoamine oxidase measured in vivo by positron emission tomography using L-[11C]deprenyl. AB - The distribution of carbon-11-labeled L-deprenyl, an irreversible inhibitor of monoamine oxidase type B (MAO-B), was determined in the baboon brain by positron emission tomography. The irreversible blood-to-brain transfer constant (influx constant, Ki) was measured using a complete metabolite-corrected arterial plasma concentration curve. This influx constant was used as a measure of functional enzyme activity for sequential determinations of MAO-B recovery following a single high dose of unlabeled L-deprenyl. The half-life for turnover of MAO-B was thus determined to be 30 days. Using appropriate irreversible inhibitors, this procedure should be generally useful for determining enzyme turnover rates in any organ in vivo and can be applied to some human studies as well. PMID- 3110377 TI - Different proteins are induced by alpha- and gamma-interferon in hairy cell leukemia. AB - Despite the striking antiproliferative effect of alpha-interferon (alpha-IFN) in hairy cell leukemia, gamma-interferon (gamma-IFN) does not appear to have such an effect. We have previously demonstrated the induction of synthesis of specific proteins by alpha-IFN, both in vitro and in vivo. We have now shown that gamma IFN induces synthesis of specific proteins, but the pattern differs from that seen after alpha-IFN exposure. The prominent 80,000-dalton protein induced by alpha-IFN was not induced by gamma-IFN, and the prominent 62,000-dalton protein induced by gamma-IFN was only rarely induced by alpha-IFN. Two other proteins were induced by both alpha-IFN and gamma-IFN. The other proteins induced by alpha IFN were not induced by gamma-IFN. These differences may be related to the different biological response of hairy cells to the two types of IFN. We also showed for both alpha-IFN and gamma-IFN that some IFN-induced proteins are probably transported to the nucleus of the hairy cell, although the majority of proteins induced by both alpha-IFN and gamma-IFN were in the cytosol/membrane fraction of the cell. We have therefore demonstrated that gamma-IFN does have a biochemical effect on hairy cells in terms of induction of specific protein synthesis, leading to the inference that hairy cells must possess another receptor at least functionally analogous to the type II IFN receptors on fibroblasts, with which gamma-IFN interacts. PMID- 3110378 TI - Gamma-interferon: physiology and speculation on its role in medicine. AB - Gamma-interferon appears to be a pivotal molecule in the immune system. Recombinant DNA technology has permitted the cloning and expression of the gene for gamma-interferon (gamma-IFN), leading to an exponential increase in the level of knowledge both in vitro and in vivo. Laboratory evidence suggests a clinical role for gamma-IFN in collagen vascular disease, chronic granulomatous infectious diseases, hematology, and medical oncology. Phase I trials have identified the toxicities; these toxicities are primarily clinical and include fever, fatigue, flu-like symptoms, and hypotension. Antitumor activity has been noted in the early development of the drug. PMID- 3110379 TI - Phase I/II trial of recombinant gamma-interferon in patients with renal cell carcinoma: immunologic and biologic effects. AB - Thirteen patients with metastatic renal cell carcinoma were entered on a Phase I/II trial of recombinant gamma-interferon (gamma-IFN). Patients (3) were entered on escalating dose levels, and each patient was escalated to the next dose until an individual maximum tolerated treatment dose (MTD) was established. Multiple parameters of biologic response were measured. Patients were studied twice baseline and at frequent intervals after the initial treatment and every treatment until the patient's individual MTD was reached. The MTD for most patients was less than 75 X 10(6) U/m2. Small, but statistically significant, enhancement of monocyte antibody-dependent cellular cytotoxicity and mononuclear cell inhibition of MBL-2 growth were noted in vitro at gamma-IFN concentrations greater than 250 U/ml. Clinically obvious biologic effects were observed: fever, chills, hypotension, and malaise. However, laboratory assays of peripheral blood mononuclear cell natural killer cell activity, tumor (MBL-2) growth inhibition, antibody-dependent cellular cytotoxicity, lymphoblastic T-cell subsets, and 2'5' oligonucleotide synthetase were not altered in vivo. PMID- 3110380 TI - Non-specificity of anti-carbonic anhydrase C antibody as a marker in human neurooncology. AB - Because the presence of carbonic anhydrase C (CA C) has been demonstrated in the oligodendrocytes of the mouse, rat and man, anti-CA C serum has been considered to be a possible specific marker for these cells. In order to determine its value in human neurooncology, specimens from 110 human tumors from the central and peripheral nervous systems as well as from five cases of cerebral infarction and two of multiple sclerosis were tested immunohistochemically by the peroxidase antiperoxidase method with anti-CA C serum. Reactive astrocytes, oligodendrocytes in the neural parenchyma surrounding tumors, and neurons included in areas of neoplasia showed CA C immunopositivity. In 92% of the astrocytomas and 56% of the glioblastomas variable numbers of tumor cells were positive. Some tumor cells positive for glial fibrillary acidic protein in ependymomas and astroblastomas were also CA C-positive. Schwannomas (86%), neurofibromas (100%) and meningiomas (86%) showed CA C positivity of the tumor cells, as did choroid plexus papillomas and gangliogliomas. However, all the medulloblastomas, neuroblastomas, central neurocytomas or melanomas tested in this study were entirely CA C-negative. In some examples of squamous cell carcinoma, leiomyoma, leiomyosarcoma and fibrous histiocytoma, CA C-positive neoplastic cells were also demonstrated. Our findings indicate that since various types of neoplastic and reactive cells express CA C positivity, the anti-CA C serum cannot be used as a specific marker for any tumor in human neurooncology. PMID- 3110381 TI - Increased dopamine efflux from striatal slices during development and after nigrostriatal bundle damage. AB - Dopaminergic control over striatal targets appears to be retained in rats sustaining lesions of the nigrostriatal dopamine (DA) system as long as 5-10% of that projection remains. Similarly, during postnatal development, dopaminergic control over striatal neurons matures well before the innervation of striatum by the nigrostriatal bundle is attained. These observations suggest that enhanced efficacy of dopaminergic transmission may compensate for hypoinnervation of striatum after lesions or during development. To examine this hypothesis, striatal slices were superfused with Krebs bicarbonate buffer and effluent was collected and analyzed for endogenous DA. Electrical field stimulation (2 Hz) continuously delivered to slices prepared from intact adult rats increased DA efflux to 3-5 times the prestimulation rate within 10 min. Efflux then fell to approximately twice the basal rate over the next 20 min. DA efflux was also examined using slices prepared from adult animals given 6-hydroxydopamine 2-3 weeks earlier, and from 7-10-d-old rat pups. In each group, striatal DA levels were 10-40% of adult control values. Nevertheless, stimulated DA efflux from these slices attained the same rate as that observed with intact, adult slices. Thus, fractional DA efflux from these slices was several times higher than the control rate by the end of the stimulation period. This increased DA efflux appeared to be a consequence of both increased release and decreased reuptake of DA, as the fractional DA efflux from control striatal slices could not be increased to the rate seen in hypoinnervated slices using nomifensine (10 microM), an inhibitor of DA efflux.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110382 TI - Effect of total parenteral nutrition upon intracranial pressure in severe head injury. AB - Animal investigations suggest that administration of hyperosmolar total parenteral nutrition (TPN) solutions may potentiate cerebral edema following head injury. Intravenous nutrition (TPN) is often required after head injury due to intolerance to enteral feeding (EN). This study evaluates the effect of TPN on intracranial pressure (ICP) measurements in severely brain-injured patients. Ninety-six severely brain-injured patients were randomly assigned to receive TPN or EN and were studied from hospital admission until 18 days postinjury. The TPN was started within 48 hours postinjury and the EN was started when tolerated. Peak daily ICP was not significantly different on admission and over time (overall mean +/- standard error of the mean 32.01 +/- 1.62 for TPN versus 32.5 +/- 1.25 for EN). Intracranial pressure was greater than 20 mm Hg in 75% of TPN patients and 73% of EN patients. Conventional therapy failed to control elevated ICP in 36% of TPN patients and 38% of EN patients. Of these patients, subsequent barbiturate therapy failed to control ICP in 56% of TPN patients and 64% of EN patients. Serum osmolality was not significantly different between groups at admission or over the course of the study. The TPN group tended to have higher mean serum glucose levels for the first 13 days postinjury, while the EN group had a higher mean serum glucose content thereafter, but these differences were not statistically significant. This study shows that TPN can be given safely to the severely brain-injured patient without causing serum hyperosmolality or affecting ICP levels or ICP therapy. PMID- 3110383 TI - gamma-Butyrobetaine hydroxylase activity is not rate limiting for carnitine biosynthesis in the human infant. AB - Carnitine biosynthesis was assessed in human infants by measuring changes in plasma carnitine concentration and rates of urinary carnitine excretion after infants were fed carnitine-free formulas with and without added epsilon-N trimethyl-L-lysine or gamma-butyrobetaine. This study was undertaken to test the hypothesis that carnitine biosynthesis in the human infant is regulated by substrate availability rather than activity of gamma-butyrobetaine hydroxylase, the final enzyme in the carnitine biosynthetic pathway. Ten infants were fed carnitine-free formula supplemented with either 500 microM epsilon-N-trimethyl-L lysine or 500 microM gamma-butyrobetaine for 14 d. Plasma carnitine concentration and rate of urinary carnitine excretion were measured in infants before and after this period. Plasma carnitine concentration increased twofold when infants were fed either epsilon-N-trimethyl-L-lysine and increased threefold when infants were fed gamma-butyrobetaine. The rate of carnitine excretion doubled when infants were fed epsilon-N-trimethyl-L-lysine and increased 30-fold when infants were fed gamma-butyrobetaine. Absorption of epsilon-N-trimethyl-L-lysine was verified by demonstrating increased urinary excretion of epsilon-N-trimethyl-L-lysine in infants fed this substrate. We conclude that gamma-butyrobetaine hydroxylase activity is not rate limiting for carnitine biosynthesis in the human infant. Development of renal and hepatic gamma-butyrobetaine hydroxylase activity was determined in necropsy tissue from individuals of various ages. It was verified that gamma-butyrobetaine hydroxylase activity is developmentally regulated in the liver, but not in the kidney. The clinical relevance of this observation is diminished in view of the results of the in vivo studies of carnitine biosynthesis in infants. PMID- 3110384 TI - Effect of dietary ascorbic acid, cholesterol and PCB on cholesterol concentrations in serum and liver in a rat mutant unable to synthesize ascorbic acid. AB - The effect of ascorbic acid deficiency and excessive ascorbic acid intake on serum and liver levels of cholesterol and lipids was investigated in ODS-od/od (OD) rats fed a normal diet, a cholesterol-containing diet or a polychlorinated biphenyl (PCB)-containing diet. The OD rat is a rat mutant unable to synthesize ascorbic acid. In OD rats, the dietary requirement of ascorbic acid to maintain normal growth and normal levels of cholesterol in serum and liver is about 300 mg of ascorbic acid/kg diet. In control (ODS-+/+) rats that can synthesize ascorbic acid, dietary addition of 0.5% cholesterol and 0.25% cholic acid caused elevation of cholesterol concentrations in serum and liver, elevation of total lipids in liver and reduction of the ratio of high density lipoprotein (HDL) cholesterol to total cholesterol in serum. Dietary addition of PCB (200 mg/kg diet) caused elevation of serum concentration of cholesterol and of the ratio of HDL cholesterol to total cholesterol in serum. In OD rats fed a normal diet, ascorbic acid deficiency slightly elevated serum concentration of cholesterol, elevated liver concentration of cholesterol and reduced the ratio of HDL-cholesterol to total cholesterol in serum; and ascorbic acid excess did not affect serum and liver concentrations of cholesterol and the ratio of HDL-cholesterol to total cholesterol in serum. In OD rats fed a cholesterol-containing diet, ascorbic acid deficiency elevated serum and liver concentrations of cholesterol, and did not affect the ratio of HDL-cholesterol to total cholesterol in serum; and ascorbic acid excess did not affect serum and liver concentrations of cholesterol and the ratio of HDL-cholesterol to total cholesterol in serum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110385 TI - Relationship between mean airway pressure, cardiac output, and organ blood flow with normal and decreased respiratory compliance. AB - We investigated the relation between blood flow and mean airway pressure in two groups of anesthetized newborn piglets. The first group had normal respiratory compliance; the second group had pulmonary surfactant depleted by repeated saline lavage, which decreased static respiratory compliance by 42%. In the normal group, cardiac output decreased linearly from 292 +/- 43 mL/min/kg at 5 cm H2O airway pressure to 134 +/- 37 ml/min/kg at 20 cm H2O airway pressure, a drop of 43% (r2 = 0.79). Blood flow to the heart, kidney, and intestines had a similar decline, but brain, hepatic artery, and adrenal flow were constant. Mean arterial blood pressure did not decrease significantly until the highest airway pressure was reached, whereas sagittal sinus pressure increased as mean airway pressure increased. In contrast, the surfactant-depleted group maintained cardiac output up to a mean airway pressure of 15 cm H2O. At 20 cm H2O, cardiac output fell to 40% of the original value. Blood flow to the heart and kidneys fell at a mean airway pressure of 20 cm H2O; intestinal blood flow decreased beginning at 10 cm H2O. As in the normal piglets, brain, hepatic arterial, and adrenal blood flow were not affected by increasing ventilation pressure. Our data show that positive pressure ventilation in the neonate has important cardiovascular effects that are blunted when respiratory compliance is decreased. More important, because cardiac output decreased prior to a significant decline in arterial blood pressure, these data suggest that in a clinical setting considerable cardiovascular alterations can occur before a decline in arterial blood pressure is detected. PMID- 3110386 TI - Carbon dioxide elimination during high-frequency jet ventilation. AB - The effects of frequency, tidal volume, and inadvertent positive end-expiratory pressure (PEEP) on CO2 elimination were studied in rabbits during high-frequency jet ventilation by measuring CO2 concentration of expired gas using a mass spectrometer. Increasing tidal volume augmented CO2 elimination (P less than 0.01 to 0.001) at each frequency, but when larger tidal volumes were associated with high inadvertent PEEP, CO2 elimination decreased despite the increase in minute ventilation. For constant minute ventilation, CO2 elimination decreased with increasing frequencies. Occurrence of inadvertent PEEP was related to increases in both frequency and tidal volume. If PEEP was controlled, no decrease in CO2 elimination was observed at the larger tidal volume. When PEEP was controlled, changes in tidal volume explained 67.1% to 95.4% of the variance in CO2 elimination not attributable to frequency. Frequency explained very little additional variance (0.1% to 13.8%). CO2 elimination comparable to estimated CO2 production occurred when tidal volumes equal to or smaller than the equipment dead space were used. We conclude that although tidal volume has a greater effect than frequency on CO2 elimination, mechanisms of gas exchange other than bulk gas transport occur during high-frequency jet ventilation. PMID- 3110387 TI - Extracellular fluid volume changes in very low birth weight infants during first 2 postnatal months. AB - Serial extracellular volume (ECV) changes were measured in 18 infants of less than 32 weeks gestation. Results were compared with changes in body weight, fluid and sodium intake, urine output, and serum sodium concentration. Mean +/- SD ECV decreased from 550 +/- 116 mL/kg on day 1 to 359 +/- 66 mL/kg on day 14. Thereafter, mean ECV/kg remained between 336 +/- 42 and 349 +/- 54 mL/kg. Clinical hydration and serum sodium concentration usually remained normal during this reduction of stabilization of ECV/kg. Six episodes of hyponatremia occurred at 11 to 31 days of age. Mean ECV/kg was significantly lower in infants with hyponatremia compared with infants of similar age with normal serum sodium concentration (303 +/- 36 mL/kg vs 368 +/- 56 mL/kg, P less than 0.01). Sodium intake in the two groups was similar. We conclude that ECV in the VLBW infant decreases postnatally and is regulated within a range similar to that in older infants, and that postnatal natriuresis in the first 2 weeks of life represents physiologic reduction of the expanded ECV of the fetus. Late hyponatremia may indicate excessive sodium loss and ECV depletion. PMID- 3110388 TI - Immunologic priming to capsular polysaccharide in infants immunized with Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine. AB - Thirty children vaccinated at 2 to 17 months of age with Haemophilus influenzae type b polysaccharide linked to a partially purified 40,000 dalton outer membrane protein of Neisseria meningitidis were revaccinated 10 to 14 months later with conventional H. influenzae type b polysaccharide vaccine. The geometric mean anti type b antibody concentration before reimmunization was 0.68 micrograms/mL, and rose to 31 micrograms/mL in sera obtained 1 month later. The mean level after immunization was not significantly different than that in sera from 12 adults immunized with type b polysaccharide vaccine (51 micrograms/mL, P = 0.3), and was 10-fold higher than that of 13 control children immunized with type b polysaccharide for the first time (2.7 micrograms/mL, P less than 0.001). The IgG responses of the children first given conjugate vaccine and then conventional type b polysaccharide vaccine were of a similar magnitude as those in the immunized adults. Further, the children maintained high levels of serum antibody 6 to 8 months later. Ten other children vaccinated in infancy with conjugate vaccine, and again with conjugate vaccine 10 to 15 months later, showed similar antibody responses to those of the group given conjugate vaccine in infancy, and booster with conventional polysaccharide vaccine. Thus vaccination with H. influenzae type b polysaccharide-outer membrane protein conjugate vaccine primes the immune system to an IgG memory antibody response to either type b polysaccharide or conjugate vaccine. Post-booster sera from all children tested showed high titers of functional activity in a complement-mediated bactericidal assay. These data suggest that protection of most infants from type b Haemophilus disease may be achieved by a combination of immunization at 2 to 4 months of age with this conjugate vaccine, and reimmunization 1 year later with conjugate or conventional type b polysaccharide vaccine. PMID- 3110389 TI - Fulminant hepatitis in children in Taiwan: the important role of hepatitis B virus. AB - In a recent period of 64 months, fulminant hepatitis was diagnosed in 17 children at National Taiwan University Hospital. Eleven patients were younger than 12 months of age. Hepatitis A IgM antibody and delta-antibody were negative in all 17. Eleven (65%) patients had hepatitis B core IgM antibody, fulminant hepatitis B. Two to 5 months before onset of hepatitis. Five of the 11 children had received blood transfusions. Three of the five donors had hepatitis B e antibody (anti-HBe) and were hepatitis B virus DNA-negative hepatitis B surface antigen (HBsAg) carriers; another two were HBsAg negative, screened by a less sensitive reverse passive hemagglutination method. The mothers of all six infants younger than 6 months of age had HBsAg. HBe antigen and antibody were studied in five of these six mothers; all five had anti-HBe. We conclude that hepatitis B virus is the most important cause of fulminant hepatitis in children in Taiwan. PMID- 3110390 TI - Anagyrine-induced red cell aplasia, vascular anomaly, and skeletal dysplasia. PMID- 3110391 TI - Nitroglycerine ointment as aid to venous cannulation in children. PMID- 3110392 TI - Efficacy of lactase-treated milk for lactose-intolerant pediatric patients. PMID- 3110393 TI - Ontogeny of phytohemagglutinin-induced gamma interferon by leukocytes of healthy infants and children: evidence for decreased production in infants younger than 2 months of age. PMID- 3110394 TI - Simplification and standardization of dot-ELISA for human schistosomiasis mansoni. AB - Dot-ELISA, a technique that shares the same principles as the enzyme immunoassay, is useful for detection of anti-Schistosoma mansoni antibodies in the sera of patients with Schistosoma mansoni infections. The antigens were fixed to the nitrocellulose strips, blocked with 1% bovine serum albumin in 0.05% Tween 20. Patient sera (40) and normal laboratory personnel sera (9) were applied to the sheet directly, without cutting the strips into small discs. The nitrocellulose sheets are kept in a humid chamber for 30 min and then washed. After incubation with peroxidase-conjugated goat anti-human antibody, washing, and addition of substrate, positive reactions appear as brown dots against the white background. The room temperature assay takes about 2 hr. The optimum antigen concentration is 20-80 ng per dot and the optimum serum dilution is 1:100-1:400. The sensitivity and specificity of the assay are 90-95% and 90%, respectively. The level of positivity of the dot-ELISA by an arbitrary scale compares with standard micro ELISA. The single positive reaction in a normal serum sample in dot-ELISA is also positive in micro-ELISA. Cross-reactivity between the S. mansoni antigen and human fascioliasis sera was noticed in 2 out of 8 patient sera. Good correlation between the arbitrary level of dot-ELISA and the absorbance of standardized micro ELISA shows that the dot-ELISA is useful both for laboratory and field studies. PMID- 3110395 TI - Detection of antibodies against the glycolipid fraction of Trypanosoma cruzi in infected mice. PMID- 3110396 TI - Survival of Sarcoptes scabiei (De Geer) stored in three media at three temperatures. PMID- 3110397 TI - Synonymy of haemoproteids of Ciconiidae. PMID- 3110398 TI - Enzyme-linked immuno-filtration assay (ELIFA) for the detection of IgG, IgM, IgA and IgE antibodies against Aspergillus fumigatus. AB - The enzyme-linked immuno-filtration assay (ELIFA) permits detection of serological precipitating systems preformed by immunoelectro-diffusion on cellulose acetate strips and simultaneous characterization of immunoglobulins G, M, A and E specific for antigens of Aspergillus fumigatus. We selected 36 sera from 9 patients who were followed up regularly and who suffered from aspergilloma (5 cases), allergic bronchopulmonary aspergillosis (2 cases), Aspergillus bronchitis and invasive aspergillosis (one case each). All of them possessed an IgG-reactive band with chymotrypsin activity. Four different IgE bands were found by ELIFA; one of them was common to all the patients who had anti-A. fumigatus IgE (7 cases out of 9). The IgA and IgM antibodies found in 7 cases out of 9 were both recognized by the same antigenic component but these fractions were distinct from those reacting with the IgE. PMID- 3110399 TI - Effect of phenothiazines, disodium ethylenediaminetetraacetic acid and diethyl maleate on in vitro rat colonic transport of cefmetazole and inulin. AB - An in vitro rat colonic sac method developed in this study was found to be suitable for frequent collection of samples and determination of transport of compounds from serosal and mucosal medium, since the volume of both was large. Under no a treatment condition, both cefmetazole and inulin penetrated the intestinal mucosa via the paracellular route, but did so very poorly. Phenothiazines as well as disodium ethylenediaminetetraacetic acid increased the transport of cefmetazole and inulin, probably via the paracellular route, while diethyl maleate increased the transport of only cefmetazole, probably via the intracellular route. The effect of phenothiazines in increasing the clearance rate for both cefmetazole and inulin showed dependency on their initial concentrations in the mucosal medium with maximum action at a concentration of 30 microM for trifluoperazine, 20 microM for perphenazine, 75 microM for profenemine and 50 microM for propericiazine. PMID- 3110400 TI - Possible mechanisms for the enhancement of rectal absorption of hydrophilic drugs and polypeptides by aqueous polyacrylic acid gel. AB - The mechanisms of absorption enhancing effect by polyacrylic acid gel were investigated in rats. Polyacrylic acid gel significantly enhanced rectal absorption of phenol red, a hydrophilic compound. The enhanced absorption was concentration dependent in the range of 0.01-0.05% w/v polyacrylic acid in gel. The gel also significantly increased the influx and the net influx on water movement in rat rectum. Further, the histological change in rectal epithelium after administration of the polyacrylic acid gel was examined with transmission electron microscopy. The structural changes, which were removal of the mucus and fenestrations of the intercellular spaces 5 and 10 min after administration of polyacrylic acid gel, were observed. These changes were reversible and returned relatively soon to normal levels. Thus, the absorption promoting effect by polyacrylic acid gel may occur mainly with increased water influx as a driving force. PMID- 3110401 TI - Inhibition of brain adenylate cyclase by barbiturates through the effect on the interaction between guanine nucleotide-binding stimulatory regulatory protein and catalitic unit. AB - The effect of barbiturates on an adenylate cyclase system in rat brain was examined. The activity of the catalytic unit of this system isolated from the synaptic membrane was inhibited by phenobarbital in dose- and time-dependent manners. The mode of the inhibition was non-competitive with respect to Mg adenosine triphosphate (ATP). The activity of the synaptic membrane-bound adenylate cyclase was also inhibited by phenobarbital in a similar manner. The inhibitory effect of phenobarbital was more potent on the activation of the enzyme by 5'-guanylylimidodiphosphate (GppNHp) than on the basal enzyme activity. The inhibitory effect, however, was not observed in the synaptic membrane preparation in which the guanine nucleotide-binding stimulatory regulatory protein (Ns) and the catalytic unit of adenylate cyclase system had been functionally coupled by pretreatment with GppNHp. Similar results were obtained with other pharmacologically active barbiturates. These findings indicate that barbiturates primarily affect the activation of the catalytic unit by an interaction with Ns resulting in the inhibition of the enzyme activity. PMID- 3110402 TI - Immunohistochemical characterization of rat pineal dopamine beta-hydroxylase containing structures: use of a homologous monoclonal antibody. AB - Previous immunohistochemical studies using a polyclonal heterologous antibody to dopamine-beta-hydroxylase (DBH) (EC 1.14.17.1) have shown that only a few of the many sympathetic nerve fibers in the rat pineal display DBH-like immunoreactivity. This is in contrast to other sympathetically innervated organs. To ascertain this observation and to rule out antibody- or method-related artifacts, in the present study a well-characterized, monospecific, homologous monoclonal antibody to DBH was used in combination with the biotin-streptavidin fluorescein-mediated detection system. As in a previous study, immunoreactive fibers were only rarely encountered in the rat pineal gland, with an identical distribution pattern. The present findings indicate that the sympathetic nerve fibers in the rat pineal gland appear to have a low capacity for de novo synthesis of noradrenaline and that most of the noradrenaline present may be taken up from the general circulation. In addition to nerve fibers, perikarya like cells and endbulb-like structures were seen in the pineal gland similar to those demonstrated by the polyclonal antibody. It is suggested that both structures may be part of an as yet unknown intrapineal regulatory system. PMID- 3110403 TI - The role of copper(I)-nicotinic acid complex on kojic acid biosynthesis by Aspergillus flavus. AB - Addition of cooper-monovalent-nicotinic acid complex to a synthetic medium specific for kojic acid production by Aspergillus flavus enhanced the production by about 47%. The substance is proposed to act via a biochemical utilization of the copper(I)-B3 complex in a manner similar to that of the naturally utilized nicotinic acid. NAD and NADP like carriers with higher reactivity have been predicted. According to this prediction the biosynthetic route of kojic acid has been interpreted on the basis of a model proposed by Bajpai et al. (1981). In this model the enzymes participating are dependent on NAD and NADP (glucose dehydrogenase and gluconate dehydrogenase) as well as on other reduction processes. PMID- 3110404 TI - Controlled-release drug delivery of diphosphonates to inhibit bioprosthetic heart valve calcification: release rate modulation with silicone matrices via drug solubility and membrane coating. AB - Calcification (CALC) is the most frequent cause of the clinical failure of bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium. The present investigation describes the formulation, characterization, and the in vivo efficacy of prolonged controlled-release silicone matrices containing the anticalcification agent disodium 1,1-hydroxyethylidene diphosphonate (Na2EHDP). Controlled release of EHDP was regulated by codispersions of Na2EHDP and the less soluble salt Ca2EHDP. Prolonged and constant release rates (zero-order) were obtained by coating silicone matrices with permeable silicone membranes, which were prepared by leaching with acetone pre-embedded polyethyleneglycol. All EHDP-containing matrices (co-implanted subdermally with BHV cusps in rats) significantly inhibited BHV CALC without detectable adverse effects on bone mineral and calcium metabolism. Matrices containing Na2EHDP:Ca2EHDP ratios of 10:90 or greater with respect to Na2EHDP completely inhibited CALC. Significant inhibition of BHV CALC was also observed with prereleased matrices (5 months in vitro), thus demonstrating prolonged efficacy. It is concluded that sustained release of effective anticalcification therapy without side effects was achieved by using codispersions of calcium and sodium EHDP salts, and that a delayed and/or constant release rate of EHDP was obtained by coating reservoir-type matrices with silicone membranes that were pre-embedded with polyethyleneglycol. PMID- 3110405 TI - Absorption and disposition kinetics of cromolyn sodium and the influence of inhalation technique. AB - Plasma concentrations of cromolyn sodium (SCG) have been measured in 13 normal subjects on three occasions after inhalation from a Spinhaler (20 mg) delivery system under conditions of controlled inspiratory flow rate. High inspiratory flow rates were associated with high peak plasma concentrations and areas under the plasma concentration-time curve. A 10-sec breath hold at the end of inspiration did not alter significantly the plasma concentration-time curve. Instillation of SCG (1 mg) directly into a second-order bronchus of 14 patients undergoing diagnostic examination gave plasma concentration-time curves similar to those seen in normal volunteers at high inspiratory flow rates. Additional studies in normal volunteers showed that SCG was poorly absorbed from the gastrointestinal tract. The shorter terminal half-life seen after i.v. infusion compared with inhalation indicates that the drug shows absorption rate limited disposition kinetics after inhalation. These studies in large numbers of subjects support the conclusions of limited earlier investigations that SCG is absorbed slowly but almost completely from the airways, that there is little gastrointestinal absorption of SCG, that only a small proportion of the Spinhaler dose (about 10%) reaches the airways and that the amount reaching the airways is related directly to inspiratory flow rate. PMID- 3110406 TI - Effects of verapamil and nitroglycerin on coronary and systemic hemodynamics in conscious dogs. AB - Effects of i.v. bolus administration of verapamil (10-300 micrograms/kg) and nitroglycerin (0.01-30 micrograms/kg) on coronary and systemic hemodynamics were studied in chronically instrumented conscious dogs. Verapamil in a dose of 10 micrograms/kg dilated the large epicardial coronary artery, increased the coronary blood flow and heart rate and decreased the aortic pressure. A reduction of left ventricular dP/dt was observed when over 30 micrograms/kg of verapamil was administered. Nitroglycerin in a dose of 0.01 micrograms/kg dilated the large epicardial coronary artery. Other variables such as coronary blood flow, aortic pressure and heart rate were influenced when over 0.1 micrograms/kg of nitroglycerin was given. The effects of these drugs on coronary and systemic hemodynamics were augmented when incremental doses were given. Duration of the increases in coronary diameter and coronary blood flow persisted longer after verapamil than after nitroglycerin. To estimate the changes in coronary diameter, independent of flow change, the effects of verapamil (100 micrograms/kg) and nitroglycerin (20 micrograms/kg) on the large epicardial coronary artery were reexamined when the coronary blood flow was maintained constant using a cuff occluder. The extent of coronary artery dilation, unaffected by coronary blood flow, was 62% with verapamil and 100% with nitroglycerin. Thus, although nitroglycerin preferentially and flow-independently dilates the large epicardial coronary artery, dilation of the large epicardial coronary artery after verapamil is augmented by the process of flow-induced arterial relaxation. PMID- 3110407 TI - Regulation of striatal enkephalin turnover in rats receiving antagonists of specific dopamine receptor subtypes. AB - The hypothesis that striatal dopamine regulates enkephalin (ENK) synthesis is supported by the increase of striatal proenkephalin mRNA and ENK after intranigral injection of 6-hydroxydopamine. In order to elucidate which dopamine receptor subtype is operative in the regulation of the dynamic state of ENK, the effect of drugs that block D-1 or D-2 receptor selectively was studied. Daily administration of 140 mumol/kg s.c. of the D-2 antagonist I-sulpiride twice daily for 2 weeks produces a 30% decrease in the content of striatal proenkephalin mRNA and ENK. In contrast, a 50% increase was observed after 2 weeks of treatment with the D-1 antagonist SCH 23390 at 74 nmol/kg s.c. three times a day. Hence, it can be inferred that the endogenous activation of D-1 tonically decreases striatal ENK synthesis. Removal of this neurally mediated regulation either by a specific pharmacologic blockage of D-1 or by lesioning with 6-hydroxydopamine increases the biosynthesis of ENK. The increase of ENK biosynthesis elicited by denervation with 6-hydroxydopamine cannot be due to the endogenous activation of D-2 receptors and must be due to the inactivation of the tonic inhibition exerted by D-1 receptors. PMID- 3110408 TI - Comparison of antigen and Ca++-ionophore-induced peptidoleukotriene release from guinea pig lung preparations using high-performance liquid chromatography. AB - This study was undertaken to investigate antigen-induced peptidoleukotriene release from lungs of sensitized guinea pigs using a recently developed solid phase extraction and high-performance liquid chromatography assay system. This release was compared to the response due to Ca++-ionophore (A23187) challenge. Incubation of lung fragments (0.6 g) from actively sensitized guinea pigs with ovalbumin (3 micrograms/ml) for 20 min at 37 degrees C resulted in the release of 40 to 60 ng of leukotriene (LT)D4 detected in the extracted filtrate (40-50% recovery of LTD4). The amount of LTD4 determined using the high-performance liquid chromatography assay correlated well with the quantity determined by a LTC4 radioimmunoassay. LTD4 release was saturable and was optimal at a tissue concentration of 0.6 g/2.5 ml of buffer. Kinetic analysis of LT generation showed that after antigen challenge, LTC4 levels peaked at 3 min and declined rapidly with time; LTD4 levels then increased significantly, reaching a maximum at 15 min and decreased slightly at 60 min. LTE4 was not detected until 30 min after antigen challenge after which it increased slowly. The kinetic results permit an estimation of the rate of LTD4 and LTE4 formation to be 5 and 0.17 ng/min/g of lung, respectively. In contrast to antigen challenge, LTD4 release from Ca++ ionophore-stimulated lung fragments was not saturable and was biphasic with increasing amounts of tissues. Moreover, LTD4 produced by Ca++-ionophore stimulation could not be detected during the first 10 min but thereafter increased linearly with incubation time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110409 TI - Valuable: LP/VNs are cost-effective caregivers. PMID- 3110410 TI - Influence of short days on diurnal patterns of serum gonadotrophins and prolactin concentrations in the male Djungarian hamster, Phodopus sungorus. AB - Exposure to short days for 8 weeks suppressed mean serum concentrations of FSH, LH and prolactin compared to hamsters kept in long days. Hamsters in short days exhibited a small afternoon rise in serum FSH, but serum LH and prolactin did not exhibit 24-h variations. In hamsters under long days, a late afternoon-early evening increase was evident for circulating prolactin but none was detected for the gonadotrophins. A fall in testes weights rapidly occurred by 14-28 days after transfer to short days. This was accompanied or preceded by a decrease in serum gonadotrophins and prolactin. Reductions in serum FSH and LH occurred in short days in blood samples taken at 09:00 h or 15:00 h. However, the nadir in serum prolactin was first achieved (at 09:00 h), at least 7 days before that at 15:00 h (i.e. Day 14 versus Day 21 of short photoperiod, respectively). The ability to secrete gonadotrophins was further tested in hamsters that had undergone gonadal regression. Castration of hamsters exposed to short days or injected with melatonin in the afternoon, a treatment known to mimic short day effects, induced a 3- to 5-fold increase in serum gonadotrophins. However, this rise in FSH and LH was significantly attenuated compared to the 10-fold response in controls in long days. The results indicate that gonadal involution induced by short days may be mediated by the decline in mean gonadotrophin secretion which, in turn, is regulated by responsiveness to steroids, as well as a mechanism independent of the negative feedback action of gonadal steroids. PMID- 3110411 TI - Long-term stimulatory effects of a continuous infusion of LHRH agonist on testicular function in male red deer (Cervus elaphus). AB - Red deer stags were infused continuously with the LHRH agonist buserelin at 180 270 micrograms/day (1.2-1.8 micrograms/kg/day) for 72 days starting in late winter with the aim of suppressing reproductive function and inducing premature casting of the antlers. Contrary to expectation, the treatment resulted in a long term stimulation of testicular activity lasting at least 2 months; the increases in plasma concentrations of testosterone were associated with an increase in aggressive behaviour and the development of rutting odour in the urine. The stags cast their antlers at the normal time in spring after the end of the treatments. The results indicate that the pituitary gonadotroph cells in the stag can continue to secrete LH in response to chronic exposure to an LHRH agonist and do not become rapidly desensitized. The effect of the agonist is therefore to cause significant stimulation of testicular activity which is a conspicuous response in the non-breeding season when the stags are already in a hypogonadal state. PMID- 3110412 TI - Hormone responses to low-dose GnRH treatment in post-partum beef cows. AB - Acyclic beef cows received 1.0, 2.5 or 5.0 micrograms GnRH/2 h for 48 h as 24 X 2 h repeated i.v. injections or by continuous i.v. infusion. Preovulatory-type LH surges were detected in 9/18 injected and 8/15 infused cows and occurred 30.6 +/- 5.1 h and 3.3 +/- 0.7 h after the start of treatment respectively. Cows receiving the lowest infusion dose did not exhibit gonadotrophin surges. The LH response to individual injections increased with dose but the proportion of injected cows showing preovulatory-type surges at each dose level did not change. A total of 20 cows (10 injected and 10 infused) showed evidence of luteal activity within 7 days of the end of GnRH treatment, although this was transitory in most animals. Cows which exhibited preovulatory-type LH surges in response to treatment had significantly higher plasma oestradiol-17 beta concentrations and lower FSH concentrations before treatment than those which did not. The results suggest that the LH response to GnRH treatment is dependent on follicular status in the immediate pretreatment period. PMID- 3110413 TI - Season influences FSH concentration in ovariectomized Ile-de-France ewes. AB - Ile-de-France ewes were ovariectomized during anoestrus or the mid-luteal phase of an oestrous cycle (day of ovariectomy = Day 0). In a short-term study, FSH concentrations were measured in blood samples collected hourly the day before and on Days 1, 3, 7 and 15 after ovariectomy (10 ewes per group). FSH concentrations increased significantly from 6.1 to 16.5 ng/ml within 1 day of ovariectomy and increased further to 47.1 ng/ml by Day 15. Differences between seasons of ovariectomy were not significant. In a long-term study, FSH concentrations were measured in blood samples collected hourly on Days 7, 15, 30, 60, 90, 120, 150 and 180 after ovariectomy in anoestrus or the breeding season (10 ewes per group). Further samples were taken (5 ewes/group) at 240 and 365 days after ovariectomy. The pattern of change in FSH after ovariectomy differed between the two seasons and the interaction between season and sampling day was significant. For ewes ovariectomized during anoestrus, FSH concentrations increased to a maximum by Day 180 and remained high thereafter. In contrast FSH increased more slowly in ewes ovariectomized in the breeding season and differences between the groups were significant from Day 90 to Day 270. However, both groups had similar FSH concentrations at Day 365. These results show that FSH concentrations increase rapidly after ovariectomy. There are seasonal differences in FSH concentrations in the absence of ovarian feedback with increases in FSH concentration around the time of the onset of the breeding season. Once FSH concentrations had reached a maximum, major seasonal changes were no longer apparent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110414 TI - Effect of local heating of the rat testis on the levels in interstitial fluid of a putative paracrine regulator of the Leydig cells and its relationship to changes in Sertoli cell secretory function. AB - Rat testes were exposed to heat (43 degrees C) for 15 or 30 min to induce moderate or severe disruption of spermatogenesis, respectively. Over 3-42 days after treatment, testicular morphology and weight, the serum concentrations of FSH and the concentrations in interstitial fluid of testosterone, androgen binding protein (ABP) and a factor(s) capable of stimulating Leydig cell testosterone secretion were monitored. Moderate seminiferous tubule damage induced by 15 min heat exposure caused a small decrease (20%) in testicular weight, but did not affect the other measures, other than transiently. In contrast, after exposure of testes to heat for 30 min there was a major and progressive decline in testicular weight throughout the experimental period, reaching 39% of control values by 42 days. In these animals, the serum concentrations of FSH were significantly increased (P less than 0.01) throughout the period of study as also where the serum and interstitial fluid concentrations ABP (P less than 0.05-0.01) and levels of interstitial fluid factor (P less than 0.01). It is concluded that the activity of the interstitial fluid factor(s) can be increased by inducing severe but selective disruption of spermatogenesis, whereas moderate disruption has no effect. Moreover, as ABP secretion into interstitial fluid was increased after severe but not moderate disruption, this suggests that in such animals proportionately more ABP may be secreted via the base of the Sertoli cell. The parallel changes in activity of the interstitial fluid factor(s) and concentrations of ABP in interstitial fluid also provides further circumstantial evidence that these products may have a common (Sertoli cell) origin. PMID- 3110415 TI - Endurance exercise potentiates the stimulatory influence of oestrogen progesterone on LH and FSH release in the rat. AB - Ovariectomized rats were treated with oestradiol benzoate and progesterone or GnRH. Prolonged exercise (running 4 days per week for 6 weeks) markedly potentiated the oestrogen/progesterone-induced release of LH and FSH, but the pituitary response to an injection of GnRH was unaffected. In contrast, at 24 h after a single exercise bout there was no apparent effect on steroid and GnRH stimulated LH and FSH responses although an acute exercise session given on the day of the LH surge inhibited steroid-induced LH release in some rats. We conclude that strenuous, prolonged exercise-training in the ovariectomized rat seems to modify the ability of the hypothalamus to release GnRH. The results were not attributable to a single bout of exercise since the gonadotrophin responses immediately or 24 h after such exercise did not parallel the results observed in the trained rats. PMID- 3110416 TI - Effects of weekly and daily pretreatment with gold sodium thiomalate on adjuvant induced arthritis. AB - The effect of gold sodium thiomalate on adjuvant induced arthritis in DA rats was investigated. Ten mg/kg gold given in either weekly or daily injections before the administration of adjuvant was able to decrease the severity of arthritis in these animals. One mg/kg gold given as daily injections had no effect on adjuvant induced arthritis. One mg/kg gold given as weekly injections before adjuvant administration reduced the severity of arthritis to a level which was intermediate between that seen in the placebo control and the 10 mg/kg gold groups. The proliferative responses of spleen cells to mitogens in these animals were not altered by in vivo gold therapy. PMID- 3110417 TI - Variation in physical and biological properties of solid gold sodium thiomalate on dissolution: an electron microscopic and energy dispersive spectroscopic study. AB - The dissolution of solid gold sodium thiomalate (GSTM) in water results in loss of yellow color. We studied the initial reaction on dissolution. It was associated with the disappearance of 2 absorption peaks on ultraviolet spectrum, one a well defined peak at 335 nm and the other a shoulder at 370 nm. This solution caused platelet aggregation and on transmission electron microscopy, dense gold containing particles measuring 125 nm are seen. Within 10 min of onset of dissolution, no gold containing particulate matter was detectable on electron microscopy. By 20 min, fibrillar particles measuring 40-150 nm appear. These resembled in general morphology and element composition the particles seen within aurosomes in platelets treated with Myochrysine (GSTM) and in synovium and other tissues by other workers. Our data elaborate on previous physical and chemical studies and correlate with morphological variations of gold containing particles at different phases. These variations in GSTM may be due to polymer size and/or structural change within the polymer. The biochemical significance of our data should provide better understanding of the biological effects of these gold thiol compounds in vivo. PMID- 3110418 TI - Antibody to cardiolipin, lupus anticoagulant, and fetal death. AB - We compared the concordance and predictive powers of activated partial thromboplastin time (APTT) and of IgG and IgM antibody to cardiolipin (aCL), for predicting fetal death in 50 pregnant women with systemic lupus erythematosus (SLE) and/or lupus anticoagulant. Overall concordance of any abnormal determination of aCL during pregnancy with any abnormal determination of APTT was 76% (0.05 less than p less than 0.10). Fetal death occurred in 6/12 (50%) of patients with high APTT compared to 5/20 (16%) of patients with low APTT; fetal death occurred in 10/13 (77%) of patients with abnormal aCL and in 2/37 (5%) of patients with normal aCL. Sensitivity for predicting fetal death was .55 for APTT and .85 for aCL; specificity was .81 for APTT and .92 for aCL. Abnormalities of APTT and aCL are sufficiently frequently discordant to prevent equation of the 2 assays. ACL is the better assay for predicting fetal death. PMID- 3110419 TI - Inhibition of fibrosis in TSK mice by blocking mast cell degranulation. AB - The Tsk mouse has a genetically transmitted connective tissue disease whose skin lesions resemble those of scleroderma. After treatment with disodium cromoglycate, a marked decrease in skin fibrosis was observed, raising the possibility that disodium cromoglycate may be a potential treatment for human scleroderma. PMID- 3110420 TI - Association between family medicine residents' personality and laboratory test ordering for hypertensive patients. PMID- 3110422 TI - Calcium paradox-evoked release of prostacyclin and immunoreactive leukotriene C4 from rat and guinea-pig hearts. Evidence that endogenous prostaglandins inhibit leukotriene biosynthesis. AB - The purpose of this study was to assess the influence of the calcium paradox (5 min calcium-free perfusion followed by 15 min calcium repletion) on the release of immunoreactive leukotriene C4 and 6 Keto-prostaglandin F1 alpha from rat and guinea-pig hearts. Under control conditions or during the 5 min calcium-free perfusion period no immunoreactive leukotriene C4 was detectable in the coronary effluent. Following reperfusion with calcium-containing medium a large release of leukotriene C4 was observed although the amount was significantly greater in the rat heart. 6 keto-prostaglandin F1 alpha was detected during normal and calcium free perfusion and the release was significantly stimulated during calcium repletion. Treatment with ibuprofen, a cyclo-oxygenase inhibitor, prevented the release of 6 keto-prostaglandin F1 alpha but increased the efflux of immunoreactive LTC4 during calcium repletion. Arachidonic acid, the substrate for prostaglandin and leukotriene synthesis increased the efflux of 6 keto prostaglandin F1 alpha but decreased the release of leukotriene C4. The latter effect was reversed by perfusion with ibuprofen, and mimicked by prostacyclin, the primary cardiac prostaglandin. This study shows that the calcium paradox is a potent stimulus for eicosanoid release from rat and guinea-pig hearts, a phenomenon likely due to the activation of calcium-dependent enzymes. The study also suggests that endogenous prostaglandins inhibit leukotriene synthesis in cardiac tissue. PMID- 3110421 TI - Ionic dependence of amino-acid transport in the exocrine pancreatic epithelium: calcium dependence of insulin action. AB - Rapid unidirectional transport (15 sec) of L-serine and 2-methylaminoisobutyric acid (MeAIB) was studied in the isolated perfused rat pancreas using a dual tracer dilution technique. Time-course experiments in the presence of normal cation gradients revealed a time-dependent transstimulation of L-serine influx and transinhibition of MeAIB influx. Transport of the model nonmetabolized System A analog MeAIB was Na+ dependent and significantly inhibited during perfusion with 1 mM ouabain. Although transport of L-serine was largely Na+ independent, ouabain caused a time-dependent inhibition of transport. Influx of both amino acids appeared to be inhibited by the ionophore monensin but unaffected by a lowered extracellular potassium concentration. Removal of extracellular calcium had no effect on influx of the natural substrate L-serine, whereas stimulation of transport by exogenous insulin (100 microU/ml) was entirely dependent upon extracellular calcium and unaffected by ouabain. Paradoxically, exogenous insulin had no effect on the time-course of MeAIB influx. The characteristics of L-serine influx described in earlier studies together with our present findings suggest that insulin may modulate the activity of System asc in the exocrine pancreatic epithelium by a calcium-dependent mechanism. PMID- 3110423 TI - Nucleotide sequence of the delta-beta-globin intergenic segment in the macaque: structure and evolutionary rates in higher primates. AB - A 5600-base-pair (bp) fragment including the beta-globin gene and about 4000 bp of its 5' flanking sequence was cloned from the DNA of Macaca cynomolgus (an Old World monkey), and the 5' flanking region was sequenced. Comparison with human, chimpanzee, mouse, rabbit, and Xenopus orthologous sequences reveals a tandemly repeated sequence called RS4 at the same position (about 500 bp 5' from the transcription start of the adult beta-globin gene) in all six species. We suggest that a tandemly repeated sequence has been maintained by functional constraints since the divergence between amphibians and reptiles. Excluding tandemly repeated sequences as well as about 400 nucleotides upstream from the cap site, the average base substitution frequencies among human, chimpanzee, and macaque intergenic sequences were calculated. They appear to be strongly correlated with the delta T50 values measured between the corresponding nuclear DNAs. They are also similar to base substitution frequencies calculated by Chang and Slightom (1984) at the pseudo-eta-globin locus. Thus, exclusion of sequences involved in specific modes of variation might allow the use of intergenic sequences for the accurate calculation of genetic distances. Using a time scale based on the dating of the Atlantic split, we estimate the base substitution rate of primate noncoding DNA to be 1.0 X 10(-9) substitution/site/year. PMID- 3110424 TI - Nucleotide sequence of the beta-globin genes in gorilla and macaque: the origin of nucleotide polymorphisms in human. AB - Part of the beta-globin genes of Macaca cynomolgus and Gorilla gorilla has been cloned and sequenced. Ten putatively neutral nucleotide polymorphisms have been described at the beta-globin locus in humans. They are associated in seven combinations, which define seven different haplotypes of the beta-globin gene: four major frameworks--1, 2, 3, and 3--and three minor frameworks, which we term KI1, KA1, and OR1. The nucleotide sequences of these frameworks are compared with those of homologous sequences in chimpanzee, colobus, macaque, and gorilla. This comparison provides strong evidence that framework 2 was the earliest framework in the human lineage. From framework 2, a rooted parsimonious tree for the six other frameworks is constructed. This phylogenetic tree is discussed in terms of the evolution of nucleotide polymorphisms as well as in terms of genetic affinities between human populations. For each position at which there is base difference in comparing human, gorilla, and chimpanzee beta-globin genes, the phyletic lineage where the corresponding substitution occurred has been identified using the maximum parsimony procedure. The data provide evidence that polymorphisms may represent a significant component of differences between closely related species. If so, nucleotide polymorphisms may strongly bias estimates of small evolutionary distances. PMID- 3110425 TI - Molecular evolution and phylogeny of the human AIDS viruses LAV, HTLV-III, and ARV. AB - A phylogenetic tree for the human lymphadenopathy-associated virus (LAV), the human T-cell lymphotrophic virus type III (HTLV-III), and the acquired immune deficiency syndrome (AIDS)-associated retrovirus (ARV) has been constructed from comparisons of the amino acid sequences of their gag proteins. A method is proposed for estimating the divergence times among these AIDS viruses and the rates of nucleotide substitution for their RNA genomes. The analysis indicates that the LAV and HTLV-III strains diverged from one another after 1977 and that their common ancestor diverged from the ARV virus no more than 10 years earlier. Hence, the evolutionary diversity among strains of the AIDS viruses apparently has been generated within the last 20 years. It is estimated that the genome of the AIDS virus has a nucleotide substitution rate on the order of 10(-3) per site per year, with the rate in the second half of the genome being double that in the first half. PMID- 3110426 TI - Models of nearly neutral mutations with particular implications for nonrandom usage of synonymous codons. AB - The population dynamics of nearly neutral mutations are studied using a single site and a multisite model. In the latter model, the nucleotides in a sequence are completely linked and the selection schemes employed are additive, multiplicative, and additive with a threshold. Although the third selection scheme is very different from the first two, the three schemes produce identical results for a wide range of parameter values. Thus the present study provides a general theory for the population dynamics of nearly neutral mutations because the results can also be used to draw inferences about other selection schemes such as stabilizing selection and synergistic selection. It is shown that the number of slightly deleterious mutations accumulated in a sequence can be considerably larger under the multisite model than under the single-site model, particularly if the sequence is long or if the mutation rate per site is high. The results show that even a very slight selective difference between synonymous codons can produce a strong bias in codon usage. Three alternative explanations for the strong bias in codon usage in bacterial and yeast genes are considered. The implications of the present results for molecular evolution are discussed. PMID- 3110427 TI - Mutagenicity tests of the antithyroid agent thiamazole. Cytogenetic studies on male mice. AB - The mutagenic potential of thiamazole, an antithyroid agent, was investigated by an in vivo cytogenetic test and was compared with those of mitomycin C and vincristine. These drugs were subcutaneously injected into slc-ICR male mice either as a single dose or as multiple doses for 5 successive days. Thiamazole (90 or 180 mg/kg) did not increase the number of micronuclei in bone marrow cells. This drug also did not induce chromosomal aberrations in spermatogonium, spermatocyte, or bone marrow cells. On the other hand, mitomycin C (3.0 mg/kg) increased the appearance of chromosomal aberrations and micronuclei. Vincristine (0.2 mg/kg) induced bone marrow cells with a so called large micronucleus (d greater than or equal to D/4). These results suggest that thiamazole may not have significant effects on the genetic systems of mice. PMID- 3110428 TI - Cytogenic analysis of dominant lethal effects of mitomycin C and ethyl methanesulfonate. AB - To gain further insight into the mechanism of induction of dominant lethal mutations, the relationship between chromosome aberrations in bone marrow and in male germ cells after treatment with mitomycin C (MMC) and ethyl methanesulfonate (EMS) was examined. In addition, we obtained fertilized eggs from the oviducts of crossbred female mice in the same way as in the dominant lethal mutation test, and examined chromosome aberrations in male pronuclei. MMC 2.5 and 5.0 mg/kg, EMS 175 and 350 mg/kg were given subcutaneously to slc-ICR mice. It was concluded that MMC causes a decrease in the sperm count by killing germ cells, which in turn causes an increase in the number of unfertilized eggs and preimplantation egg loss. MMC seems also to cause invisible damages in the chromosomes of spermatocytes which lead to dominant lethality. EMS induced chromosome damage in the post-meiotic germ cells, and this damage, in turn, produced chromosome aberrations in the eggs, resulting in a high incidence of dominant lethality. PMID- 3110429 TI - Effect of thyrotropin-releasing hormone injected into lateral ventricle on respiration and blood pressure in rabbits. PMID- 3110430 TI - The dodecahedral framework of the bacteriophage phi 6 nucleocapsid is composed of protein P1. AB - The outer layer of the bacteriophage phi 6 nucleocapsid (NC) was removed by EDTA and reassociated with the core in the presence of Ca2+ or Mg2+. The core was relatively inaccessible to trypsin digestion, was composed of protein P1, and was in the dodecahedral framework reported previously. (H.T. Steely, Jr., and D. Lang, J. Virol. 51:479-483, 1984; Y. Yang and D. Lang, J. Virol. 51:484-488, 1984). The double-stranded RNA genome became RNase sensitive after EDTA treatment of the nucleocapsid. PMID- 3110431 TI - The role of vesicostomy in the management of anterior urethral valves in neonates and infants. AB - We performed vesicostomy as the initial form of management in 2 male newborns and 1 infant with anterior urethral valves associated with proximal urethral diverticula and bilateral hydronephrosis. Prompt improvement in the degree of hydronephrosis was noted after vesicostomy in all 3 patients along with improvement in renal function in 2 who had presented with renal insufficiency. Subsequently, 2 patients have undergone vesicostomy closure and transurethral valve fulguration, and 1 also required ureteral reimplantation for persistent vesicoureteral reflux. The use of vesicostomy in the newborn period rather than transurethral fulguration prevented the potential complications of urethral stricture and inadequate valve resection that can occur owing to the small size of the neonatal urethra. Furthermore, a period of vesicostomy drainage before eventual ureteral reimplantation for severe vesicoureteral reflux obviated the need for ureteral tailoring. PMID- 3110432 TI - Percutaneous endoscopic fulguration of a large volume caliceal diverticulum. AB - Currently, the optimal approach to a caliceal diverticulum appears to be direct puncture into the diverticulum with subsequent dilation and stenting of the narrow ostium with a large nephrostomy tube. However, further maneuvers might be necessary in cases of large volume caliceal diverticula. We describe a patient with a large caliceal diverticulum (7.5 cm.) in whom percutaneous endoscopic fulguration was used successfully as an additional technique to assure obliteration of the diverticulum. PMID- 3110433 TI - Generalized hypersensitivity reaction to intravesical thiotepa and doxorubicin. AB - We describe an unusual case of pruritus after intravesical thiotepa, and diaphoresis, shortness of breath, chills and pruritus following intravesical doxorubicin therapy. Such generalized allergic reactions occur uncommonly after bladder instillation of thiotepa or doxorubicin. PMID- 3110435 TI - Lower extremity cyanosis: an unusual presentation of congenital paraureteral diverticula. AB - Congenital bladder diverticula are an uncommon cause of urinary retention in children. We report on a male infant with bilateral congenital bladder diverticula that compressed the posterior urethra causing urinary retention and also compressed the venous return from the lower extremities producing cyanosis. PMID- 3110436 TI - Acute nonlymphocytic leukemia after thiotepa instillation into the bladder: report of 2 cases and review of the literature. AB - We report 2 cases of acute nonlymphocytic leukemia after thiotepa instillation into the bladder for superficial bladder carcinoma and review 4 additional cases from the literature. Intravesical thiotepa is absorbed systemically in patients with bladder carcinoma and such treatment may be associated with the rare occurrence of acute nonlymphocytic leukemia and/or the myelodysplastic syndrome. PMID- 3110437 TI - Assessment of vitamin status in patients undergoing acute nutritional repletion. PMID- 3110434 TI - Diverticulum of the female urethral roof managed endoscopically. AB - We report a rare case of a diverticulum located along and draining into the roof of the urethra in a woman. This diverticulum was managed successfully endoscopically with a pediatric resectoscope. The pathophysiology of this unusual lesion is discussed, as is the rationale for endoscopic management. PMID- 3110438 TI - Treatment effects of parenteral vitamins in total parenteral nutrition patients. AB - To determine the prevalence of abnormal vitamin levels in an adult hospitalized population requiring total parenteral nutrition (TPN) and to assess the effect of routine parenteral vitamin therapy on vitamin levels, we studied 35 general surgical patients. Assays for 12 vitamins were performed both before and after a standard 10-day course of TPN. Patients were given nothing by mouth. The first 25 patients received a daily parenteral vitamin mixture tailored to the recommendations of the Nutrition Advisory Group of The American Medical Association (maintenance dose). The final 10 patients were given a parenteral multivitamin dose providing substantially greater amounts of most vitamins (repletion dose). Only 58% (190/324) of pre-TPN vitamin levels were normal, 25% were low, and 17% were high. No patient had fewer than two abnormal baseline levels. Vitamin levels did not correlate with serum albumin, body weight, or nitrogen balance. After 10 days of treatment, only 39% of low pre-TPN vitamin levels improved; most (45/62) of the low posttreatment levels were low at baseline. The higher repletion dose resulted in a significantly (p less than 0.01) greater percent increase in vitamin A, C, and pyridoxine levels. The prevalence of abnormal vitamin levels in this population is high (42%). Standard parenteral vitamin therapy leads to marginal improvement in abnormally low pre TPN vitamin levels. PMID- 3110440 TI - Water-soluble vitamins in cancer patients on parenteral nutrition: a prospective study. AB - Forty-three patients with mild weight loss were studied prospectively to determine whether the parenteral water-soluble vitamin doses in a commercially available preparation (MVI concentrate; USV Laboratories, Tarrytown, NY) maintained serum, red blood cell (RBC), and urinary concentrations of water soluble vitamins in stressed cancer patients receiving total parenteral nutrition (TPN). Patients were divided into three groups: (1) oral diet, no intravenous vitamins given; (2) TPN plus 5 ml MVI; and (3) TPN plus 10 ml MVI. Vitamins C, B1, B2, B3, B6, and niacin were measured initially and weekly during a 6-week study period. Caloric and nitrogen balances were quantified. Most of the patients in all three groups had normal blood or urine levels of all water-soluble vitamins. No clinical evidence of vitamin deficiency or MVI toxicity was detected. The recommended parenteral dosages of vitamin C (100 mg/day) and B3 (15 mg/day) provided measurably adequate levels in all patients. Levels of vitamins B1, B2, B6, and niacin that were less than the normal range were noted in 4-40% of patients receiving the recommended daily dosages of 3 mg, 3.6 mg, 4 mg, and 40 mg, respectively. These deficiencies appeared to improve in group III patients who received twice the recommended parenteral vitamin dosages, although they did not completely disappear. Niacin deficiency appeared to be the most prevalent, occurring in 40% of patients studied. Since intravenous doses of B1, B2, B6, and niacin are safe and well tolerated, it appears that increased daily amounts of these vitamins should be given to cancer patients on parenteral nutrition. PMID- 3110441 TI - Prospective evaluation of single and triple lumen catheters in total parenteral nutrition. AB - The recent introduction of triple lumen catheters has facilitated the care of seriously ill patients by providing multipurpose central venous access through a single percutaneous 7 French catheter. This prospective study was performed to examine the complications associated with the use of these catheters in patients receiving long-term total parenteral nutrition (TPN). Seventy-five patients undergoing catheterization were randomly separated into two groups: 36 patients underwent placement of a single lumen catheter (SLC), and 39 patients, a triple lumen catheter (TLC). The two groups were comparable with respect to concomitant infections, treatment with antibiotics, and need for intensive care. Patients in the SLC group received TPN for a mean of 9.7 days and in the TLC group, for a mean of 8.5 days (p = 0.427). However, after 5 days of catheterization, there was a marked increase in the number of TLC removed because of skin entry site infections. SLC were more likely to be used for the full duration of TPN administration (p = 0.025). Catheter tips were cultured by semiquantitative techniques. A higher incidence of catheter sepsis was seen with TLC, 12.8% vs 0% with SLC (p = 0.055). TLC used for TPN are associated with higher rates of catheter entry site infections and systemic sepsis. SLC should be used for TPN administration. PMID- 3110439 TI - Maintenance of vitamin and trace element status in intravenous nutrition using a complete nutritive mixture. AB - Complete nutritive mixtures (CNM) of all intravenous nutrients including fat emulsions are being used increasingly because of their convenience. However, this may lead to chemical interactions and reduce the amount of active vitamins and trace elements made available to the patient. We have studied the effects on micronutrient status of provision of all nutrients in one 3-liter bag (CNM: amino acids, dextrose, Intralipid 20%, a nine-element trace metal mixture, and complete fat- and water-soluble vitamin mixtures) in 10 postoperative surgical patients [median intravenous nutrition (IVN) 14.5 days, range 7-38]. A similar group received the fat emulsion plus water- and fat-soluble vitamins as a separate infusion (SI) from a 3-liter bag (median IVN 14.0 days, range 8-28). Serum and urine magnesium, zinc, copper, manganese, chromium, and selenium, serum vitamins A, E, C, folate, and B12, RBC B1, B2 B6, and folate and leukocyte vitamin C were measured at weekly intervals. All patients in both groups maintained or improved their status for all the micronutrients analyzed. No significant differences between the CNM and SI groups were found in blood concentrations of any of the elements or vitamins. Only for urine copper did the CNM lead to increased excretion (1.51 +/- 0.59 mumol/24 hr; copper input 20 mumol/day), compared to SI (1.00 +/- 0.70 mumol/day, p less than 0.001 Mann-Whitney test) suggesting possible interaction. It is concluded that micronutrient status was maintained during short-term IVN with the CNM and that it did not lead to a significantly greater loss of vitamins or essential trace elements than the SI system. PMID- 3110443 TI - Central venous catheter guidewire replacement according to the Seldinger technique: usefulness in the management of patients on total parenteral nutrition. AB - While on total parenteral nutrition (TPN), 37 patients underwent replacement of a central venous catheter (CVC), during which a wire introducer was used, according to the Seldinger technique. In 25 patients, the CVC was placed in the superior cava via the subclavian, and, in 12, via the jugular vein. Overall, 82 CVC changes were performed.: 74 for assumed CVC sepsis, 6 as preventive treatment, and 2 for partial catheter displacement. Catheter tip culture proved to be positive in 25 of 119 CVC examined. The catheters were defined as sterile when the tip culture was negative; contaminated, when the tip culture was positive and peripheral blood culture was either negative or positive for different bacteria; septic when both tip and blood were positive for the same bacteria. The results indicated that 10 catheters were contaminated and 17 were septic. Eight previously sterile CVC were found positive after the exchange: 3 were removed at the end of TPN in asymptomatic patients, and 5 were successfully resterilized by means of one more change. Guidewire replacement allowed CVC sterilization of 22 of 24 catheters (91.6%). No complications due to the catheter-changing method were seen. PMID- 3110442 TI - Fate of right atrial catheters inserted prior to arrival at a transplant center. AB - An analysis of catheter-related complications in a study group consisting of 83 patients, each of whom arrived at a major marrow transplant center after having had a large bore right atrial catheter (RAC) inserted by the referring institution, was compared to a similar analysis of catheter-related complications in 357 patients who had their RAC inserted at the transplant center just before the transplant procedure was begun (control group). Fourteen (17%) patients in the study group had their original catheter removed for complications (five for septicemia and nine for mechanical complications) compared to 57 (16%) of the patients in the control group. Thirteen (16%) of the 83 catheters in the study group were double lumen and only two of these (15%) were replaced due to complications. Sixteen of 59 patients (27%), 13 years old or older, who arrived with a single lumen RAC already inserted, required an additional catheter during the transplant procedure because of an increased need for intravenous access. From this study, we concluded that patients who arrived for marrow transplantation with a RAC already inserted did not routinely need the catheter replaced. However, it is recommended that double lumen catheters be inserted in adult patients if marrow transplantation is anticipated. PMID- 3110444 TI - Double-blind study of glycerol vs glucose in parenteral nutrition of postsurgical insulin-treated diabetic patients. AB - Twenty-five insulin-treated diabetic patients were randomly assigned postoperatively to 5 days of intravenous infusions of ProcalAmine (3% amino acids, 3% glycerol, and electrolytes) or FreAmineIII + dextrose and electrolytes. The solutions were given isocalorically and isonitrogenously. Insulin was adjusted to keep glycemia at the level of 150-200 mg/dl. The ProcalAmine group by the 5th day had plasma glucose of 158 +/- 25 mg/dl and required 1.20 +/- 0.10 U/hr insulin. The FreAmine + dextrose group had plasma glucose of 169 +/- 53 mg/dl and required 2.28 +/- 0.13 U/hr. At all time points postsurgically, the ProcalAmine group required less insulin. PMID- 3110445 TI - Liver composition and histology in growing infant miniature pigs given different total parenteral nutrition fuel mixes. AB - Although young infants are at greater risk for total parenteral nutrition (TPN) related liver disease than adults, previous studies on the effect of the TPN energy source on the development of hepatic steatosis have been carried out in adult rats and adult humans. We studied the effect of a glucose and a glucose/fat TPN energy regimen on hepatic chemical composition and the development of steatosis in newborn miniature pigs. Twenty miniature pigs were randomized at 10 days of age to receive a TPN regimen which utilized either glucose (group A) or glucose/fat (group B) as the non-nitrogen energy source. After 8 days, blood was drawn for insulin, glucagon, SGPT, albumin, and bilirubin determinations. Samples of liver were obtained at 9 days. Plasma insulin levels were significantly higher and glucagon levels lower in group A piglets than in those in group B. Normal values were obtained for SGPT, albumin, and bilirubin, and no differences were found between groups. Chemical analysis of the livers revealed no differences between groups in the concentrations of glycogen, fat, protein, DNA, and RNA. Group A animals had significantly higher concentrations of water than group B (group A: 0.75 +/- 0.01 liter/kg; group B: 0.74 +/- 0.01; p less than 0.03). A significant correlation was found in group B between the plasma insulin/glucagon ratio and the hepatic glycogen concentration (r = 0.73, p less than 0.05). Group A animals had fat vacuoles in centrilobular hepatocytes, in contrast with group B animals who had visible fat only in Kupffer cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110446 TI - Studies on the tolerance of medium chain triglycerides in dogs. AB - Two groups of five conscious dogs received total parenteral nutrition (about 100 kcal/kg body weight per 24 hr) continuously for 96 hr (0.28 g triglycerides/kg body weight per hr, constituting more than 55% of the energy supply). The only difference between the two groups was the nature of the 20% lipid emulsion. In one group, this emulsion contained only long-chain triglycerides (LCTs), and in the other it contained a mixture (vol/vol) of medium chain triglycerides (MCTs) and LCTs. MCTs thus were given in an amount of about 30% of the total energy supplied. During infusion with the MCT/LCT mixture, C8, C10, and C12 fatty acids appeared in the total plasma fatty acids. When the infusion was stopped, the medium-chain fatty acids disappeared; those with shorter chains did so more rapidly. The plasma triglyceride clearance was faster for the MCT/LCT mixture than for the LCTs, whereas phospholipid and cholesterol clearance seemed slower for the MCT/LCT mixture. With this mixture, there was a slight increase in the plasma concentrations of ketone bodies, lactate, and pyruvate, and a slight decrease in plasma glucose. The MCT/LCT mixture was well tolerated, causing no discernible problems, and, in particular, no signs of narcosis or encephalopathy. PMID- 3110447 TI - Hepatic abnormalities associated with aluminum loading in piglets. AB - Cholestasis is a common complication of total parenteral nutrition (TPN) in infants. A contributing factor to the hepatic dysfunction may be a contaminant of the TPN solution, such as aluminum, that accumulates in liver and may act as a hepatotoxin. To study the hepatic effects of aluminum, growing piglets were given daily intravenous injections of aluminum, 1.5 mg/kg, for 50 days; pair-fed controls were given heparinized saline. At sacrifice, liver and serum were obtained. Liver was analyzed for histopathology and for aluminum content and localization. The hepatocyte lysosomes of the experimental group showed aluminum peaks by x-ray microanalysis, whereas the control group did not. No differences in ultrastructure were noted between the two groups when examined by electron microscopy. Mean serum total bile acid levels (27.8 +/- 15.9 SD vs 6.3 +/- 1.5 mumol/liter, p less than 0.05), mean alkaline phosphatase (309 +/- 108 vs 180 +/- 27 IU/liter, p = NS), and mean hepatic copper content (24.8 +/- 4.5 vs 14.4 +/- micrograms/g dry weight, p less than 0.01), were elevated in the aluminum-loaded piglets, indicating that cholestasis may have been produced. Also, a small but significant reduction in serum levels of 25 hydroxy-vitamin D was found in the aluminum-loaded piglets, suggesting that vitamin D hydroxylation may be impaired. Inasmuch as lysosomal contents are excreted into the bile, aluminum accumulation in lysosomes may alter lysosomal function and possibly affect bile flow or content. PMID- 3110448 TI - Effect of enteral nutrition on human pancreatic secretions. AB - The influence on pancreatic secretion of four enteral feeding products was evaluated in a unique patient with an isolated duodenal fistula for whom enteral feeding access was obtained via a gastrostomy with a small Silastic catheter passed through the gastrostomy and through a surgically created gastrojejunostomy. The patient was totally supported by intravenous nutrition during the study. Each enteral feeding solution was administered at full strength at 50 ml/hr for 2 days with a 24-hr collection of pancreatic secretions by the duodenal cutaneous fistula taken on the second day. Infusion of the enteral feeding solutions did not alter volume of fistula drainage. All solutions decreased bicarbonate and amylase secretion but increased lipase and total nitrogen excretion. From this study, it would appear reasonable to administer Vivonex HN and Criticare HN via the jejunum in patients with pancreatic disease, whereas Osmolite would appear less satisfactory, due to its much stronger stimulation of lipase secretion. PMID- 3110449 TI - Parenteral nutrition-induced anaphylaxis. AB - A case report of a 4-yr-old child who developed an anaphylactic reaction to parenteral nutrition is presented. Dermal allergy tests demonstrated a sensitivity to Travasol solution and Armour multivitamin 2 solution. This is the first reported case known to us of such a response to elemental parenteral nutrition. PMID- 3110451 TI - Cardiac tamponade in a newborn: a complication of hyperalimentation. AB - Perforation of the heart by central venous catheters is an uncommon but life threatening complication in the neonatal age group. Prevention requires an open insertion technique, the use of soft Silastic catheters, and the maintenance of the catheter tip above the right atrium. Rapid clinical deterioration with signs of tamponade suggests the diagnosis. Catheter withdrawal, early pericardiocentesis, and pericardiotomy with myocardial repair in selected cases contribute to survival. PMID- 3110450 TI - Warfarin resistance associated with intravenous lipid administration. AB - Intravenous lipids have been shown to have varying effects on coagulation parameters. A patient with short bowel syndrome and recurrent thrombotic episodes who required both intravenous lipids and anticoagulation is described. A constant infusion of a soybean oil emulsion (Intralipid) in his parenteral nutrient solution was demonstrated to interfere with the anticoagulant effect of warfarin. Termination of the infusion and rechallenge with warfarin resulted in prolongation of his prothrombin time to the therapeutic range. Reinstitution of a lipid-free parenteral nutrition regimen has allowed for successful continuation of warfarin therapy. PMID- 3110452 TI - Problems of trace elements and vitamins during long-term total parenteral nutrition: a case report of idiopathic intestinal pseudo-obstruction. AB - An 8-year-old girl with chronic idiopathic intestinal pseudo-obstruction (CIIP), who is the first case of CIIP in Japan, has been receiving total parenteral nutrition (TPN) for more than 6 years. During this time, she experienced deficiencies of copper, zinc, vitamin A, vitamin B12, folic acid, and biotin, and an excess of vitamin A; she exhibited a series of signs and symptoms due to these deficiencies and vitamin A overdosage. Nevertheless, careful monitoring of serum levels of trace elements and vitamins and appropriate therapy have almost solved these problems. She has achieved normal physical and mental development and goes to school, while receiving home parenteral nutrition with an ambulatory infusion system. PMID- 3110453 TI - The chest tube: a simple device for the tunneling of central venous catheters. AB - The chest tube is presented as a device for the tunneling of central venous catheters. It offers several advantages over currently recommended tunneling devices. It is readily available in multiple sizes to accommodate different diameter catheters, produces lengthy atraumatic tunnels, and can be bent into various shapes to facilitate passage through the subcutaneous tissues. PMID- 3110454 TI - More cost-containment literature needed. PMID- 3110455 TI - Phenobarbital therapy and parenteral nutrition. PMID- 3110456 TI - Cellular and subcellular mechanism of transient depolarization. AB - Cardiotonic steroids cause single ventricular cells to exhibit transient depolarization after a train of driven action potentials or, in voltage clamp experiments, transient inward current after a depolarizing clamp pulse. Transient depolarization or transient inward current was eliminated by an intracellular injection of EGTA. Transient depolarization was elicited by an intracellular injection of CaCl2, even in the control Tyrode's solution. Together with transient depolarization or transient inward current, digitalis intoxication promoted spontaneous oscillatory fluctuations in membrane potential or in membrane current. Their power spectra peaked at frequencies of 3-4 Hz and coincided well with the frequency of repetitive transient depolarization. The fluctuations were eliminated by intracellular injections of EGTA and decreased in amplitude by caffeine with a shift toward higher frequencies. These result suggest that an oscillatory release of Ca from intracellular storage sites is the common basis underlying both the transient events and the spontaneous fluctuations in membrane potential or current. The Ca-sensitive current, measured by intracellular Ca injection, flowed inwardly at negative potentials and reversed polarity at around -22 mV. Therefore this current component is carried by more than one ion. PMID- 3110457 TI - Use-dependent blocking action of newly developed lidocaine-analogs on maximum rate of rise of action potentials in guinea pig papillary muscle. AB - The mode of antiarrhythmic actions of the newly developed antiarrhythmic drugs, tocainide, mexiletine and SUN1165, which bear the N-2,6-dimethylbenzene ring as a common structural unit, were examined by comparing the use-dependent blocking actions on the maximum rate of rise of action potentials (Vmax) in guinea pig ventricular muscle. The time course of the use-dependent reduction of Vmax after stimulation and its recovery after cessation of stimulation were fitted by double exponential curves to avoid the effects of the rapid stimulation (2 Hz) on the level of the membrane diastolic potential. The onset rates constants of the use dependent block were 0.29 +/- 0.07 per action potential for tocainide (10(-4) M), 0.07 +/- 0.02 (mean +/- SE, n = 5) per action potential for SUN1165 (10(-5) M) and were too rapid to be accurately fitted for mexiletine (10(-5) M). The time constants of the Vmax recovery from the use-dependent block were prolonged to 0.67 +/- 0.32, 0.27 +/- 0.13 and 96 +/- 11 (mean +/- SE, n = 5) sec in the presence of tocainide, mexiletine and SUN1165, respectively. These data indicate that tocainide and mexiletine should be classified as lidocaine-like drugs, while SUN1165 may be a quinidine-like drug which interacts with Na+ channels and has slower kinetics than lidocaine-like drugs. PMID- 3110458 TI - [Instrument and technology of external radiotherapy]. PMID- 3110459 TI - [Radiobiology of cancer radiotherapy]. PMID- 3110460 TI - [Fast neutron therapy]. PMID- 3110461 TI - [Complete response of unresectable gastric cancer (Borrmann's type III) treated with combination chemotherapy of UFT and mitomycin--a case report]. AB - A 69-year-old male visited our hospital in December, 1983, complaining of dysphasia. X-ray and endoscopic examination of the stomach revealed Borrmann's type 3 of the cardia. A biopsy specimen revealed typical features of adenocarcinoma. Because the tumor could not be resected, chemotherapy was started in February, 1984 with a combination of UFT (600 mg/day) and mitomycin (6 mg/week). After five courses of the combination chemotherapy, UFT therapy was continued. Follow-up endoscopy in August, 1985, showed a discolored area of the cardia. A biopsy specimen revealed no evidence of carcinoma. UFT-M therapy is a useful chemotherapy for gastric cancer. PMID- 3110462 TI - [Refractory respiratory tract infections. 5. Persistence of chronic airway infections. a. Mechanism of etiology and persistence]. PMID- 3110464 TI - [Prevention of infection in patients with traumatic shock]. PMID- 3110463 TI - [The clinical significance of liver mitochondrial enzyme determinations in the serum for the diagnosis of drug induced liver injury]. PMID- 3110465 TI - The effect of temperature and glutaraldehyde fixation on the mechanical properties of bovine pericardial tissues. AB - A comparison is made of the elastic response of fresh pericardial tissues at 25, 37, and 42 degrees C, and also of fresh and glutaraldehyde-fixed tissues. Strips of bovine pericardial tissues cut perpendicular to the base-apex axis of the heart were used. An Instron machine was used for uniaxial tensile tests, and the strain-rate used was 666.7% X min-1. No significant differences in tissue mechanical properties were observed for temperature values of 25, 37, and 42 degrees C. However tissues fixed in a glutaraldehyde solution were more extensible than fresh tissues. The elastic responses of tissue preserved for 1 day in glutaraldehyde are not very different from those preserved for up to 10 days. PMID- 3110467 TI - Immediate CO2 storage capacity at the onset of exercise. AB - The purpose of the present study was to obtain the immediate CO2 storage capacity at the onset of exercise. The CO2 stores at the onset of the exercise were calculated from the difference between the respiratory gas exchange ratio (R) and the metabolic gas exchange ratio (RQ: R obtained at 5.5 min of exercise). The CO2 stores per body weight (CO2 stores/w) were linearly related to the CO2 pressure (P'vCO2) determined by the CO2 rebreathing method (r = 0.713, p less than 0.001), the slope being 0.330 ml/(mmHg X kg). The CO2 stores were then corrected for change in O2 stores with exercise, that defined as total CO2 stores. P'vCO2 was also corrected for the effect of lung-bag volume shrinkage and Haldane effect during CO2 rebreathing, that defined as true PvCO2. The total CO2 stores/w were also related linearly to the true PvCO2 (r = 0.725, p less than 0.001), the slope of the regression line defined as the immediate CO2 storage capacity being 0.650 ml/(mmHg X kg). PMID- 3110466 TI - Effect of airway anaesthesia on the ventilatory and heart rate responses to isocapnic progressive hypoxia. AB - The effect of airway anaesthesia by lidocaine inhalation on the hypoxic ventilatory response was examined together with the heart rate response by the isocapnic progressive hypoxia test in human subjects. During the test, end-tidal PCO2 (PETCO2) was maintained at the resting level. However, because resting PETCO2 tends to decrease by airway anaesthesia, we conducted the test at the resting PETCO2 determined both before (normocapnic) and after lidocaine (hypocapnic). Ventilatory and heart rate response were evaluated as a linear function of oxygen saturation of the arterial blood (SaO2). In the "hypocapnic" runs, ventilatory responses tended to be depressed, while the slope of heart rate response-PETCO2 relationship increased after lidocaine. However, when PETCO2 was restored to the normocapnic level, ventilation apparently increased from the control, and the augmented slope in the heart rate response disappeared. Although the elevated ventilation in normocapnic hypoxia might be due simply to the increased ventilatory response to CO2, we suggested that the augmented slope in the heart rate response in hypocapnic hypoxia might be related not only to PETCO2 level itself but also to the direct effect of airway anaesthesia. PMID- 3110468 TI - Affective disorders in mentally retarded adolescents--report of two cases with lithium treatment. AB - Two cases of moderately retarded adolescents with affective disorders have been treated for nine and five years, respectively. Rapid cycling episodes were seen in early adolescence and a long duration of episodes appeared in late adolescence. A two-year lithium therapy was able to control them fairly well but did not work as a prophylaxis. Lithium carbonate induced polydipsia or personality change. PMID- 3110469 TI - Serum prolactin, cortisol and growth hormone concentrations after various epileptic seizures. AB - The serial serum concentrations of prolactin (PRL), cortisol and growth hormone (GH) were measured after clinical fits of seizures in 49 epileptic patients, aged 13-77. In generalized tonic-clonic seizures, both the serum PRL and cortisol levels transiently rose and reached their maximum 30 min after the onset of clinical fits. Serum GHs were elevated in some of the patients. After complex partial seizures, significant rises were found only in serum cortisol, but no demonstrable change was observed in PRL and GH. In the other minor seizure group, no remarkable change was observed in any of the hormones. These results suggest that the postictal hormonal change is different in each type of seizure, respectively. PMID- 3110470 TI - Chromosome examination of patients under lithium therapy. AB - The chromosomal aberrations of 13 patients who had received continuous lithium therapy for affective disorders were examined. Healthy college women were used as controls. There was a high frequency in gaps among the patients compared with the controls, but there was no significant difference between them. Although there was a significant relationship between the age of patients and the incidence of abnormal cells, there was no relationship between the duration of lithium therapy and the incidence of abnormal cells. These results suggest that lithium carbonate has neither the suppression effect of chromosomal repair mechanisms nor mutagenic activity. In order to discuss the teratogenicity of lithium salts on human beings, it seems necessary to conduct chromosome examinations of babies born to lithium-treated women. PMID- 3110471 TI - A trial of discontinuation of barbiturates in patients with secondary generalized epilepsy. AB - The vast majority of patients with secondary generalized epilepsy (SGE) were under polytherapy including barbiturates. We were able to completely withdraw barbiturates in 17 cases with a refractory course of SGE. Valproic acid (VPA) is considered as one of the best drugs for SGE. Barbiturates decrease the serum level of VPA and this may lead to a reduced efficacy of VPA. The dosage of VPA was adjusted to attain the level of 100-150 micrograms/ml. Barbiturates were then gradually decreased and finally discontinued. After six months of follow-up, 13 patients (76%) showed a reduced seizure frequency. Also, the physical and psychological conditions improved in a good number of cases. Barbiturates are not necessarily required in pharmacotherapy of SGE and may be safely withdrawn. PMID- 3110472 TI - Blood ammonia level during valproic acid therapy. AB - We determined the blood ammonia level of epileptic patients in relation to valproic acid (VPA) therapy. A total determination of 256 specimens obtained from 174 cases were analyzed. The materials were assigned to the following three treatment groups: (a) VPA-monotherapy, (b) VPA-polytherapy and (c) non administration of VPA. The distribution ranges of the blood ammonia level (micrograms/dl) were 40.5, 56.6 and 40.7 in mean, respectively. The VPA polytherapy group showed a significantly higher level compared with the other two groups. On the other hand, the latter two groups showed no difference. There was a positive relationship between the blood ammonia and VPA serum levels with statistical significance. In conclusion, a critical factor causing hyperammonemia seemed to be the multiple use of antiepileptic drugs including VPA. PMID- 3110473 TI - Accumulation of neurofilaments in a sporadic case of amyotrophic lateral sclerosis. AB - We report a case of sporadic amyotrophic lateral sclerosis (ALS) characterized by a marked accumulation of neurofilaments in the cytoplasm of neurons. The neurofilament was identified by immunohistochemical and electron microscopic studies. The distribution of the accumulation in this case was unique, not only in the motoneurons of the anterior horn but also in the neurons of the other areas of the spinal gray matter, some nuclei in the brain stem, pontine reticular formation, substantia nigra, dentate nucleus in the cerebellum and pyramidal cells in the motor cortex. These observations shed light on the pathogenesis of ALS. PMID- 3110475 TI - [The role of transurethral cauterization and instillation of mitomycin-C on carcinogenesis of the urinary bladder]. PMID- 3110474 TI - [Diagnosis and treatment of male hypogonadism]. PMID- 3110476 TI - Abelson murine leukemia virus-induced thymic lymphomas: transformation of a primitive lymphoid precursor. AB - For the investigation of whether Abelson murine leukemia virus (A-MuLV) is able to transform in vivo lymphocytes other than those of the B-cell lineage, newborn BALB/c and C57BL/6 mice were given an injection of A-MuLV directly into the thymus. Thymic lymphomas appeared with a short latent period of 4-5 weeks in BALB/c mice and 8 weeks in C57BL/6 mice. Cell lines derived from some thymic lymphomas presented a very immature phenotype and did not express cellular markers of either T-cells (Thy 1.2, Lyt 1.2, and Lyt 2.2) or B-cells (cytoplasmic IgM) even after treatment with several differentiation inducers. Molecular analysis showed that T-cell receptor (TCR) beta chain genes were never rearranged; in one case only, rearrangement of TCR gamma chain genes could be demonstrated, confirming the immaturity of the presumptive T-cell lines studied. Furthermore, the cell lines consistently carried diversity (D)-joining (J) but not variable (V)-D-J rearrangements of the immunoglobulin heavy chain genes. On the whole, these findings suggest that following intrathymic A-MuLV injection neoplastic transformation does involve lymphocytes possibly of T-cell lineage, at a very early stage of differentiation. PMID- 3110477 TI - Modulation of cell proliferation by human recombinant interleukin-1 and immune interferon. AB - The growth-modulating effects of recombinant alpha- and beta-forms of human interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) were examined with several human cell lines. Exposure to combinations of IL-1 and IFN-gamma resulted in three categories of cell response. The first was cell lines in which IL-1 stimulated growth and offset the growth inhibitory effects of IFN-gamma. These lines included the lung carcinoma CALU-1 and the colon carcinoma SW-48. The second was some of the cell lines that were refractory to IL-1 and that were inhibited by IFN-gamma alone. These included the cervical carcinoma HeLa, the transformed milk line HBL-100, and the myelogenous leukemia K562. The third group consisted of cells in which growth inhibition by IL-1 and IFN-gamma was additive. These included the mammary carcinomas MCF-7 and MDA-MB-415. The exception to this latter group was ME-180 in which significant additive inhibitory effects could not be demonstrated. IL-1 alone primarily induced a cytostatic effect in growth inhibited cell lines. The cytolytic effect induced by IFN-gamma was increased in the presence of IL-1. The data support the conclusion that the effects on growth of IL-1 and IFN-gamma are mediated by different mechanisms. PMID- 3110478 TI - Single inhalation exposure to 90SrCl2 in the beagle dog: late biological effects. AB - Late-occurring biologic effects were studied in beagle dogs that were given graded levels of 90SrCl2 via single brief inhalation exposures and were subsequently observed for their life-span. Due to the soluble chemical form of the aerosol, 90Sr was rapidly translocated from lung and deposited in bone where it was subsequently retained for a long period of time. Radiation-induced lesions were confined to the bone, bone marrow, and adjacent soft tissue. Forty-five primary bone tumors occurred in 31 of 66 exposed dogs. Metastasis occurred from 21 tumors, with the lung being the most frequent site of metastasis (76%). Twenty seven tumors were classified as different subtypes of osteosarcoma, 14 as hemangiosarcomas, 3 as fibrosarcomas, and 1 as a myxosarcoma. Four carcinomas arising from soft tissues adjacent to bone were also considered to be 90Sr induced. In contrast to bone tumors arising in beagles chronically exposed to 90Sr through ingestion, histologic lesions of radiation osteodystrophy were minimal in this study, indicating that these lesions are not a necessary precursor of osteosarcoma development. The incidences of hemangiosarcomas (31%) and telangiectatic osteosarcomas (11%) in addition to osteosarcomas suggest that the cell of origin for all of these neoplasms is a multipotent mesenchymal cell with the potential for various morphologic expressions dependent on local environmental factors. PMID- 3110479 TI - [Prognostic importance of determining the central hemodynamic indices of patients with progressive stenocardia]. PMID- 3110480 TI - [Dynamic auscultation of the heart]. PMID- 3110481 TI - [Use of rheoencephaloplethysmography in the quantitative assessment of blood flow, modules of arterial and venous volumetric elasticity and other hemodynamic parameters of the vessels of the head]. AB - A noninvasive method has been developed for quantitative assessment of all major hemodynamic parameters in vessels of the head on the basis of symmetrical fronto occipital rheoencephaloplethysmography, using an RPG 2-02 adapter and the techniques of classical venous occlusive plethysmography. Blood flow (cm3/min), arterial and venous blood filling (cm3), and arterial and venous volume elasticity modules (dyne/cm2) are measured separately, per 100 cm3 of tissue, for the left and the right hemispheres of the brain. The method sensitivity and practicability have been confirmed by studies of nitroglycerin-induced variation in the above-mentioned parameters. PMID- 3110482 TI - Acetate metabolism and bicarbonate generation during hemodialysis: 10 years of observation. AB - The capacity of chronically hemodialyzed patients to metabolize acetate during conventional hemodialysis was evaluated using a retrospective study in 219 patients dialyzed for up to ten years under similar dialysis conditions. For each patient, and using all available data, a regression line relating the changes of plasma total CO2 during dialysis as a function of the pre-dialysis value was calculated. The intercept of this function indicates the plasma concentration where the losses of bicarbonate in the dialysate is matched by the generation of bicarbonate arising from the metabolism of acetate. This value therefore represents an individual index of the capacity of each patient to metabolize acetate. A value for this index smaller than 18.0 mM was considered abnormal. It was shown that around 10% of chronically hemodialyzed patients are clearly unable to metabolize acetate optimally. This defect is not related to the duration of dialysis, body weight or quality of hemodialysis treatments but is strongly related to sex, 19 of the 22 "acetate intolerant" patients being women. In a prospective study, all the 60 patients of the same population undergoing active dialysis were studied, and this index identified 12 abnormal (11 women, 1 man) patients and 48 normal patients. Plasma acetate measured at the end their dialysis treatments were significantly higher in abnormal than in normal patients. It is concluded: that this index is useful to identify the patients unable to metabolize acetate optimally; that only around 10% of hemodialyzed patients present a severe problem when dialyzed against acetate and should be dialyzed against bicarbonate; that dialysis against acetate does not fully correct the metabolic acidosis even in "normal" patients. PMID- 3110483 TI - Localization of angiotensin II receptors in rat and monkey kidney by in vitro autoradiography. PMID- 3110484 TI - [Side effects of valproate in epileptic children]. PMID- 3110485 TI - [Long-term decompression of the intestines in acute peritonitis and intestinal obstruction]. PMID- 3110486 TI - [Sex hormones and the hypophyseo-gonadal axis in females with liver cirrhosis in postmenopause]. AB - The hormonal status of men with cirrhosis of the liver has been investigated in numerous studies. Little, however, is known about changes of sexual hormones in women afflicted by this disorder. In a study of 31 postmenopausal women (mean age 63 +/- 8 years) suffering from cirrhosis of various etiology (alcoholic, n = 8; posthepatitic B, n = 1; PBC, n = 5; cryptogenetic, n = 17) the blood levels of estradiol (E2), estrone (E1), androstenedione (A), testosterone (T) and basal and stimulated values of gonadotropins are reported and compared with the data obtained in an age-matched control group (n = 9). In cirrhosis a significant increase of the median E2 (28 vs 12 pg/ml, P less than 0.01) was found, whereas the changes of the blood levels of E1 (88 vs 76 pg/ml), A (63 vs 111 ng/dl), and T (0.30 vs 0.15 ng/ml) did not attain statistical significance in comparison to controls. Within the study group, however, a significant positive correlation with the degree of decompensation of cirrhosis (Childscore A-C) was observed for the steroid hormones measured. Thus, in subgroup C the hormone levels are higher than physiologically expected for postmenopausal women. On the other hand the median FSH (32 vs 48 mU/ml, P less than 0.05) is significantly lower in cirrhosis compared to controls with a trend to decreased values of LH. Very low levels of LH and FSH are found in decompensated cirrhosis. The decrease of LH and FSH can partly be explained by the rise of peripheral hormones (i.e. E2, E1, and in some cases T and A).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110487 TI - A case of valproate intoxication with excessive brain edema. AB - A 29-year-old man, who had been treated with sodium valproate for 3 years because of generalized cerebral seizures, ingested a large amount of this drug in an attempt to suicide. The exact amount he had swallowed could not be determined. The patient arrived in the intensive care unit in a deep coma, was intubated, and artificially ventilated. He developed a massive cerebral edema, as proved by computerized tomography (CT). This was supported by electroencephalography (EEG). The measured value for the concentration of valproate in serum was markedly elevated on the day of admission (2300 mumol/l; therapeutic range 350-700 mumol/l). Treatment with sodium thiopental, glycerol, and glucocorticoids was initiated. A second CT scan performed 9 days after admission showed a complete normalization and the EEG yielded a markedly improved pattern. At this point the patient slowly regained consciousness. We conclude that in patients with an acute sodium-valproate intoxication, care should be taken with regard to the development of a severe cerebral edema, which in the reported case could be treated successfully. PMID- 3110488 TI - [Unapparent course of pancreatitis with pseudocyst development and cholestatic jaundice in anticonvulsive therapy with valproate]. AB - Valproic acid is a reliable and comparatively safe drug in the treatment of special forms of absence seizures. Severe but very rare complications include acute liver necrosis and acute pancreatitis which may end lethally. A case of a previously unreported association of pancreatic pseudocyst and development of cholestatic icterus in conjunction with valproic acid therapy is presented. The clinical signs of icterus and chronic pancreatic failure disappeared when we terminated the therapy. PMID- 3110490 TI - [Workplace--the sickbed]. PMID- 3110489 TI - [Diagnostic and prognostic significance of various new indicators of gastric acid production and intragastric proteolysis in patients with pre-ulcer condition and peptic ulcer]. PMID- 3110491 TI - [Aids in overcoming stress in everyday nursing]. PMID- 3110492 TI - [Repercussions under criminal law and responsibility as to liability from the viewpoint of continuing education in functional nursing]. PMID- 3110493 TI - [Work safety and protection in functional nursing from the viewpoint of the accident insurer]. PMID- 3110494 TI - [Health for all by the year 2000. Target of "Health for all". Implications for nursing and midwifery]. PMID- 3110495 TI - [Hygiene--a troublesome thing!? Beginnings of an improvement of hygienic conditions in nursing]. PMID- 3110496 TI - [Workplace--the sickbed.... Considerations on the panel discussion on 20 March, 1987 during the 7th International Meeting for Continuing Education in Nursing in Giessen]. PMID- 3110497 TI - [Report on work at the CMCH (Christian Medical College and Hospital) at Vellore/Southern India. 2]. PMID- 3110498 TI - [10 years of parenteral feeding at home]. PMID- 3110499 TI - [The hospice movement is expanding]. PMID- 3110501 TI - Suboccipital puncture for cerebrospinal fluid in the common marmoset (Callithrix jacchus). AB - Cerebrospinal fluid (CSF) can be obtained routinely from the common marmoset (Callithrix jacchus) by suboccipital puncture. One field of research in which this method is applied is the detection of changes in the biogenic amine metabolism in CSF. The puncture technique is simple and rapid and does not injure the experimental animal. PMID- 3110500 TI - Effects of Trypanosoma brucei and Babesia microti infections on the primary granulomatous reaction to Schistosoma eggs in mice. AB - Mouse infection with the blood protozoa Trypanosoma brucei suppressed significantly the frequency and intensity of the primary granulomatous inflammatory response to eggs of the blood flukes Schistosoma mansoni and S. bovis injected into the pulmonary microvasculature. In addition, the dynamics of the cellular infiltrate of the egg granuloma were strongly affected. It is suggested that the modulation of the granulomatous response is a result of impairment of the cell-mediated immunological responsiveness induced by T. brucei. Infection with Babesia microti did not induce similar effects on the granulomatous response. PMID- 3110502 TI - Visualization and biopsy of the colon in tamarins and marmosets by endoscopy. AB - Endoscopic visualization and biopsy have been performed under anesthesia in more than 65 tamarins and marmosets to study the pathogenesis of colitis and cancer of the colon. This procedure allows examination of the large bowel from the anus to the cecum and has been repeated at 2-6 month intervals with few complications. However, care must be exercised not to perforate the colon. Successful use of this technique will permit study of the pathogenesis of colonic diseases throughout the life of the animal and should provide cause-effect information about colitis and colon cancer in tamarins that may apply to the human diseases. PMID- 3110503 TI - Enteral nutrition in children. PMID- 3110504 TI - Listeria meningitis resistant to ampicillin. PMID- 3110505 TI - Biochemical consequences of protein depletion in the rabbit heart. AB - We showed previously that cardiac function was depressed in rabbits subjected to 6 weeks of protein depletion and was restored after 4 weeks of protein refeeding. To identify nutritional or metabolic factors that underlie cardiac dysfunction, we assessed the nutritional status and myocardial content of energy-providing substrates in three groups of rabbits: group I served as control; group II was fed a protein-free diet; and group III was fed a protein-free diet and then repleted. Animal weights were 2.73 +/- 0.22 kg in group I, 1.92 +/- 0.28 kg in group II, and 2.78 +/- 0.12 kg in group III. Serum albumin concentrations decreased from 3.70 +/- 0.12 g/dl in group I to 2.81 +/- 0.10 g/dl in group II, and returned to normal (3.71 +/- 0.11 g/dl) in group III. The heart weights; myocardial contents of water, nitrogen (N), total fat, and glycogen; skeletal muscle N concentrations; and liver N contents were measured. Protein depletion produced a reduction in total cardiac mass due to decreased nitrogen and glycogen contents, but there was an increased fat content. Comparison with other organs suggests that cardiac muscle plays a role in energy homeostasis, undergoing glycogenolysis and proteolysis similar to those of liver and skeletal muscle. Protein repletion restored normal mass of the heart, but not of the liver. We conclude that adequate nutrition may be important in maintaining cardiac function. PMID- 3110506 TI - Vasoactive drug effects on blood flow in internal mammary artery and saphenous vein grafts. AB - The internal mammary artery is a dynamic coronary graft, whereas the saphenous vein graft is passive. Therefore, potential exists not only for beneficial vasodilation but also for catastrophic spasm of the artery. The purpose of this study was to examine blood flow in the internal mammary and saphenous vein grafts during infusion of drugs that are commonly used after cardiac operations. A canine right heart bypass preparation allowed precise control of cardiac output, blood pressure, and heart rate, which were maintained constant during drug infusion. Both the internal mammary and saphenous vein grafts were constructed so that they perfused the same coronary bed: They were anastomosed in a Y fashion to a ligated anterior descending coronary artery. Electromagnetic flow probes measured graft flow (with the other graft occluded) before and after 15 minutes of drug infusion. The order of drug infusion was randomized and changes were compared by tests for paired differences. Phenylephrine (2 micrograms/kg/min) decreased flow in both the internal mammary and saphenous vein grafts, whereas norepinephrine (0.1 microgram/kg/min) increased flow in both grafts. Epinephrine (0.05 microgram/kg/min) increased mammary artery flow 16% +/- 6% but decreased saphenous vein graft flow 9% +/- 7%. Nitroglycerin (1 microgram/kg/min) significantly increased internal mammary flow (36% +/- 13%), from 47 +/- 7 to 59 +/- 7 ml/min (p less than 0.01), whereas flow decreased significantly in the saphenous vein graft 14% +/- 3%, from 64 +/- 9 to 59 +/- 8 ml/min (p less than 0.01). Nitroprusside (1 microgram/kg/min) decreased mammary artery flow 12% +/- 2%, from 50 +/- 7 to 44 +/- 7 ml/min (p less than 0.01), but increased saphenous vein graft flow 25% +/- 8%, from 64 +/- 9 to 77 +/- 7 ml/min (p less than 0.01). All hemodynamic variables were unchanged, except for norepinephrine, which significantly increased the first derivative of left ventricular pressure. The results suggest that flow through the canine internal mammary artery is changed by the drugs commonly used in perioperative management. Epinephrine and nitroglycerin increased internal mammary artery flow and decreased saphenous vein graft flow, whereas nitroprusside had the opposite effect. The vascular reactivity of the internal mammary artery must be considered when these drugs are used after coronary revascularization. PMID- 3110507 TI - Factor VIII-associated antigen in human lymphatic endothelium. AB - Lymphatic vascular endothelium both on tissue section and in culture exhibits positivity for Factor VIII-associated antigen although staining is generally less intense and more spotty than in comparable blood vascular endothelium. Lymphatic endothelium also exhibits Weibel-Palade bodies. Neither marker, therefore, reliably distinguishes blood vascular endothelium from lymphatic endothelium. PMID- 3110508 TI - The spectrum of IgM monoclonal gammopathy in 430 cases. AB - IgM monoclonal gammopathy consists of a broad spectrum of diseases, ranging from apparently benign to malignant conditions. In a long-term follow-up study of 430 patients in whom a monoclonal IgM serum protein had been identified, 242 (56%) had monoclonal gammopathy of undetermined significance, 71 (17%) had Waldenstrom's macroglobulinemia, 28 (7%) had lymphoma, 21 (5%) had chronic lymphocytic leukemia, 6 (1%) had primary amyloidosis, and 62 (14%) had other malignant lymphoproliferative diseases. More than two-thirds of the patients died, and the most common cause of death was a lymphoid malignant process. Almost a fifth of the patients with an apparently benign monoclonal gammopathy subsequently had a lymphoid malignant lesion (in one patient, more than 20 years after the detection of the serum M protein). The median duration of time from the recognition of the M protein until the development of a malignant lymphoid disease ranged from 4 to 9 years. An increased number of lymphocytes or plasma cells on bone marrow examination was not a reliable indicator of the likelihood of such an outcome. Thus, follow-up of these patients should be conducted indefinitely. PMID- 3110509 TI - Enzyme histochemistry of monoamine oxidase in the heart of aged rats. AB - The distribution of monoamine oxidase types A and B in the heart of young (3 month-old) and aged (26-month) Wistar rats was studied by histochemical methods. In young rats, MAO activity was higher in the left ventricle than in the right. Enzyme reactivity was present within both muscle cells and the blood vessel wall. Histochemical staining was abolished by clorgyline administration. In the heart of aged rats, we observed a very remarkable increase of clorgyline sensitive MAO activity primarily at the level of myocardial cells. The right ventricle showed the highest increase of MAO reactivity. PMID- 3110510 TI - [Chylothorax as the initial manifestation of Waldenstrom's macroglobulinemia]. PMID- 3110511 TI - [Juvenile xanthogranuloma in a flat xanthoma]. AB - A case of juvenile xanthogranuloma located on a plane xanthoma plaque in the left flank of a seven months old child is reported. Histologically we observe a typical pattern of JXG in the center of the lesion and foamy cells exclusively around the capillary vessels in the peripheric areas of the lesion. We consider that the same etiopathogenic mechanisms implicated in the JXG will produce the clinical and histologic appearance of plane xanthoma around it. PMID- 3110512 TI - Effects of droxicam on in vivo prostaglandin synthesis and ex vivo platelet aggregation. AB - Droxicam, similar to piroxicam, inhibits in vivo renal synthesis of PGF2 alpha. This study was performed in rats; droxicam and piroxicam were administered orally at doses of 0.5, 1.2 and 8 mg/kg. Inhibitory activity of the two compounds was similar (40-60%) but showed no dose-effect relationship. Maximum inhibition was obtained with the 1 mg/kg dosage. In dogs droxicam has shown a clear inhibitory effect on arachidonic acid induced ex vivo platelet aggregation. Droxicam was administered orally at a dose of 2 mg/kg. Maximum inhibition (-40%) was achieved 24 hr post-administration and the effect was sustained up to 72 hr (-23%). PMID- 3110513 TI - Circling behavior in normoxic or hypoxic rats with unilateral 6-OHDA nigrostriatal lesion. Part 1. Effects of apomorphine and L-dopa. AB - Unilateral administration of 6-hydroxydopamine (6-OHDA) into the rat nigrostriatal system provokes circling behavior in response to apomorphine and L dopa. This behavior appears to be mediated by the development in the lesioned side of a postsynaptic dopamine receptors supersensitivity. Acute hypobaric hypoxia does not modify the apomorphine-induced stimulant effects, but does oppose the L-dopa-induced circling behavior. Our data suggest that effects of hypoxia are mediated by a presynaptic mechanism. The antagonism of the effects of L-dopa cannot be explained by the inhibition of activity of the oxygen-dependent enzyme tyrosine hydroxylase, but seems to be related to an impairment of the release of newly synthesized dopamine from exogenous L-dopa. PMID- 3110514 TI - [Measuring chemiluminescence in phagocytic granulocytes--simultaneously a parameter of their killing function?]. AB - The results of the chemiluminescence activity determined in whole blood samples very often were used to compare the unspecific defense mechanism of polymorphonuclear granulocytes (PMN) against causative organisms to preoperative capable risk parameters in surgery. Our investigations try to compare the results of a bacteria-induced chemiluminescence with those we received from a standardized agar killing plate-test. It could be shown that there is no correlation between the used two test systems. Therefore it is not possible to conclude from the chemiluminescence results especially made out of whole blood samples to the potency of the defense mechanism of PMN granulocytes. PMID- 3110515 TI - [Pancreas transplantation today]. PMID- 3110516 TI - [Relation of implanted beta cell mass and metabolic status following transplantation of pancreatic fragments in the dog]. AB - 20 dogs underwent total pancreatectomy. Pancreatic fragments were produced using an intraductal collagenase perfusion technique and mechanical disruption of the pancreatic gland. The resulting tissue suspension was transplanted as an autotransplant to the spleen of each animal by intravenous reflux injection into the splenic vein. In 75% of all transplanted animals long-term function with normoglycemia was restored while i.v. glucose tolerance tests were impaired as compared to 13 controls. The spleen insulin content of these successfully transplanted animals corresponded to only 5 to 15% of the original pancreas insulin content which was responsible for the reduced function. Intraductal collagenase perfusion is a reliable method to restore normoglycemia after total pancreatectomy in the autotransplant model using pancreatic fragments. To improve the metabolic function of the islet transplant an increased number of islets has to be implanted. PMID- 3110517 TI - Cochlear patency problems in cochlear implantation. AB - Sensory deafness may be associated with partial or total obliteration of the cochlear scalae. Before undertaking cochlear implant surgery, a preoperative assessment of cochlear patency with high-resolution computed tomography (CT) is indicated. To determine the accuracy of pre-implant CT, a review of the radiographic and surgical findings in 36 implanted ears was performed. An abnormal CT scan was found to be a reliable predictor of compromised cochlear patency at operation. These findings help the surgeon to select the side most favorable for implantation and to anticipate problems that may be encountered during device insertion. A normal pre-implant CT scan, however, does not exclude the possibility of compromised cochlear patency. A 46% false negative rate was encountered, presumably because subtle degrees of osseous or fibrous obliteration of the cochlea are beyond the resolution by current generation CT scanners. In our opinion, the radiographic finding of cochlear ossification is not a contraindication to an attempt at cochlear implantation. The only assured way of determining the extent of cochlear patency is by performing an "exploratory cochleostomy" with fenestration of the basal cochlear turn. Drilling anteriorly through an ossified basal scala tympani will often expose an adequate lumen and permit insertion of even a long multichannel electrode into a partially ossified cochlea. Nevertheless, it is essential that the implant team be prepared with devices appropriate for whatever existing or surgically created lumen may be available. PMID- 3110518 TI - Laser applications in the trachea and bronchi: a comparative study of the soft tissue effects using contact and noncontact delivery systems. AB - A comparative study of laser soft tissue effects using carbon dioxide (CO2) and neodymium-yttrium aluminum garnet (Nd-YAG) lasers in contact and noncontact endoscopic delivery systems was done in the canine tracheobronchial tree to determine the best laser system for the specific disease. The CO2 laser bronchoscopic coupler, CO2 laser waveguide, Nd-YAG laser fiber, and Nd-YAG laser contact probe were used. A 5 mm diameter soft tissue injury exposing tracheal cartilage was made, and the power density for each laser modality was measured. Soft tissue effects were documented histologically using routine techniques and scanning electron microscopy acutely and at 1 week and 2 weeks after injury. The effects were similar with the CO2 laser coupler and the CO2 laser waveguide with comparable power densities. Compared with the CO2 laser, the Nd-YAG laser fiber caused more extensive and more difficult to control thermal damage in tissue. The Nd-YAG laser contact probe was capable of precise soft tissue ablation with minimal surrounding tissue damage and was associated with the most rapid healing. This study concluded that high power density with short exposures is desirable when treating benign disorders, such as tracheal stenosis, making the CO2 laser or Nd-YAG laser contact probe application a good choice. On the other hand, malignant tumors with a potential for hemorrhage are best treated with the Nd-YAG laser noncontact fiber system because of its superior coagulative effects. PMID- 3110519 TI - [Diverticulum of the female urethra: coagulum diverticulectomy]. PMID- 3110520 TI - Autoradiographic localization of [3H]-guanidinoethylmercaptosuccinic acid binding sites in rat islets of Langerhans. AB - Incubation of unfixed, frozen sections of rat pancreas with tritiated guanidinoethylmercaptosuccinic acid (GEMSA) resulted in a localization of [3H] GEMSA autoradiographic grains over the islets of Langerhans, suggesting that a carboxypeptidase H-like enzyme occurs in the islet. PMID- 3110521 TI - Valproic acid-induced neural tube defects: reduction by folinic acid in the mouse. AB - Neural tube defects were induced dose-dependently by single injections of the anticonvulsant drug valproic acid (VPA) as sodium salt in mice on gestational day 8. Folinic acid (5-CHO-THF) coadministration by i.p. injection or by a constant rate infusion via osmotic minipumps, implanted s.c., significantly reduced the exencephaly rates using a randomized double-blind experimental procedure. 5-CHO THF supplementation cut the exencephaly rates into half even at high maternal plasma levels of VPA (p less than 0.005, chi 2-test); resorption rates were not affected. The VPA plasma kinetics were not changed by any of the application regimens of 5-CHO-THF. The investigation of the folate metabolite pattern (determined by HPLC) showed that 5-CHO-THF and 5-methyl-tetrahydrofolic acid (5 CH3-THF) were the main metabolites in untreated mice. After supplementation with 5-CHO-THF, only the concentrations of this folate vitamer were increased in the plasma from 0.3 microgram/ml (normal) to 0.6 or 1.9 micrograms/ml (after injection of 3 x 1 mg/kg or 3 X 4 mg/kg) and to 4.2 micrograms/ml (after infusion via osmotic minipumps). Our results indicate that VPA-induced exencephaly in mice combined with the investigation of the plasma levels of VPA and the different folate metabolites could be an appropriate animal model to study protective effects of folates on the occurrence of neural tube defects. PMID- 3110522 TI - Adenylate cyclase activity in fish gills in relation to salt adaptation. AB - The influence of salt adaptation on specific adenylate cyclase activity (measured by conversion of [alpha-32p]-ATP into [alpha-32p]-cAMP) was investigated in gill plasma membranes of rainbow trout (Salmo gairdneri) adapted to various salinities (deionized water, DW; fresh water, FW; 3/4 sea water, 3/4 SW; sea water, SW) and in sea water adapted-mullet (Mugil sp.). Basal activity declined by a factor of 2 in trout with increasing external salinity (pmoles cAMP/mg protein/10 min: 530 in DW, 440 in FW, 340 in 3/4 SW; 250 in SW) and was very low in SW adapted-mullet: 35. The Km for ATP was similar (0.5 mM) in both FW adapted- and SW adapted- trout in either the absence (basal activity) or in the presence of stimulating agents (isoproterenol; NaF) while the Vm varied. Analysis of stimulation ratios with respect to basal levels of the enzyme showed that hormones (glucagon, VIP) and pharmacological substances (isoproterenol, NaF) display a greater potency in high salt than in low salt adapted- fish gills. In contrast, salt adaptation did not have any effect on the regulation of adenylate cyclase by PGE1. These results are interpreted in relation to the general process of osmoregulation. PMID- 3110523 TI - Naloxone accelerates the rate of ventilatory acclimatization to hypoxia in awake rats. AB - During ventilatory acclimatization to hypoxia in rats, PaCO2 progressively falls from about 40 torr in normoxia (PIO2 approximately equal to 150 torr) to a new steady-state at about 23 torr in chronic hypoxia (24 or more hours at PIO2 approximately equal to 90 torr). In acute (20 or 60 minutes) hypoxia naloxone treatment caused a hyperventilation greater than that caused by acute hypoxia alone. Following 20 minutes hypoxia, naloxone treated rats had a PaCO2 = 28.6 +/- 0.7 torr (mean +/- 95% confidence limits) which was significantly lower (P less than .001) than the saline treated PaCO2 = 31.0 +/- 0.6 torr. In contrast, in normoxia and at 24 hour hypoxia and at 20 minute return to normoxia following 24 hours hypoxia, naloxone treatment had no effect on PaCO2. We conclude that in the rat about one third of the ventilatory acclimatization to hypoxia is due to a progressively decreasing endogenous opioid-like inhibition of ventilation. PMID- 3110524 TI - RO 15-1788 decreases hypnotic effects of sleep deprivation. AB - The present study investigated the effects of 5 mg, 60 mg and 120 mg of the benzodiazepine antagonist RO 15-1788 on the ability to resist sleep and on mood of sleep deprived subjects. Repeated administration of 60 and 120 mg significantly increased subjects alertness in comparison with 5 mg and placebo. The 5 mg dose had a tendency to potentiate the hypnotic effects of sleep deprivation. The higher levels of the drug also decreased positive mood and increased negative mood, and increased the density of sleep spindles during sleep. These results are interpreted to suggest a dose dependent effect of RO 15 1788 on arousal level. PMID- 3110525 TI - Stimulation of prostaglandin E2 production by phorbol esters and epidermal growth factor in porcine thyroid cells. AB - Effects of phorbol esters and epidermal growth factor (EGF) on prostaglandin E2 production by cultured porcine thyroid cells were examined. Both phorbol 12 myristate 13-acetate (PMA) and EGF stimulated prostaglandin E2 production by the cells in dose related fashion. PMA stimulated prostaglandin E2 production over fifty-fold with the dose of 10(-7) M compared with control. EGF (10(-7) M) also stimulated it about ten-fold. The ED50 values of PMA and EGF were respectively around 1 X 10(-9) M and 5 X 10(-10) M. Thyroid stimulating hormone (TSH), however, did not stimulate prostaglandin E2 production from 1 to 24-h incubation. The release of radioactivity from [3H]-arachidonic acid prelabeled cells was also stimulated by PMA and EGF, but not by TSH. These results indicate that both PMA and EGF are potent stimulators of prostaglandin E2 production, associated with the activity to stimulate arachidonic acid release in porcine thyroid cells. PMID- 3110526 TI - Human macrophages degrade tryptophan upon induction by interferon-gamma. AB - Human peripheral blood mononuclear cells, monocytes-macrophages and T-cells were stimulated with human recombinant interferon-gamma, interferon-alpha and phytohemagglutinin. The culture supernatants were analyzed for tryptophan, kynurenine, 3-hydroxyanthranilic acid, anthranilic acid and neopterin by high performance liquid chromatography. Tryptophan was decreased and the four other compounds were increased in supernatants of peripheral blood mononuclear cells activated by interferon-gamma (250 U/ml), interferon-alpha (10.000 U/ml) and phytohemagglutinin (1 microgram/ml). After splitting of peripheral blood mononuclear cells by adherence, the monocytes and macrophages but not the T-cells degraded tryptophan upon stimulation by interferon-gamma in a dose dependent manner. Supernatants of phytohemagglutinin stimulated but not of resting T-cells were found to induce tryptophan degradation by macrophages, the active principle being neutralized by an antiserum for interferon-gamma. Thus phytohemagglutinin acts by activating T-cells to release interferon-gamma which in turn induces macrophages to degrade tryptophan. In all experiments the appearance of neopterin in the culture media was correlated to the observed tryptophan degradation. PMID- 3110527 TI - Undrugged rotational response in nigro-striatal system-lesioned rats is related to the previous early response to apomorphine when repeatedly administered. AB - Development and time-course characteristics of undrugged rotational response weeks or months after repeated apomorphine administration in 6-hydroxydopamine lesioned rats were explored. In one series of experiments, all groups received several drug doses two-three weeks post-lesion and remained undrugged at different intervals from the last drug injection. Weeks or months later, they were injected with saline in the same environment where they previously had received apomorphine. In this way we studied acquisition, time-course and extinction of the rotational response after saline. Furthermore, we related this undrugged response which does not fully develop until two weeks after treatment, and which previously had not been related to a specific parameter of the rotational response to the drug, to a critical point of the time-course response to the drug, i.e., the early rotational response in the first minute after injection. This early response is a learning phenomenon based on the environmental cues where drug has been repeatedly administered. Finally, we state the concept of pharmacological conditioning using this animal model of Parkinson's disease, in agreement with our own results and the previous results of Silverman and Ho (1981). PMID- 3110529 TI - Hypercholesterolemia and the baboon cerebral circulation. AB - We investigated cerebrovascular vasodilator responses to increased arterial CO2 and the cerebrovascular response to infused 5-hydroxytryptamine (5-HT) in normal and hypercholesterolemic baboons. After 6-8 weeks of feeding an atherogenic diet the plasma cholesterol levels were increased without change in the triglycerides. The hypercholesterolemic animals showed a higher basal systemic arterial blood pressure than the normal controls without significant decrease in cerebrovascular prostacyclin production, altered basal cerebral blood flow or altered cerebrovascular response to infused 5-HT. However, the vasodilator response to hypercapnia was significantly decreased from the control value of 2.78 ml/min per mmHg increase in PCO2, to 1.62 ml/min per mmHg. Thus functional impairment of cerebral hemodynamics occurred before atherosclerotic alteration in the cerebral vessels could have been present. PMID- 3110528 TI - Effect of ethanol on thromboxane and prostacyclin synthesis by fetal platelets and umbilical artery. AB - The effect of ethanol (10-500 mmol/l) on platelet thromboxane production and on vascular thromboxane and prostacyclin was studied in human fetal tissues. The release of thromboxane B2 (a metabolite of thromboxane A2) during thrombin induced spontaneous aggregation of fetal platelets was inhibited by ethanol concentrations of 50 mmol/l or higher. Ethanol at concentration from 100 mmol/l also inhibited umbilical artery production of thromboxane B2 and that of 6-keto prostaglandin F1 alpha (a metabolite of prostacyclin). However, it stimulated the conversion of exogenous arachidonic acid to thromboxane B2 in fetal platelets and to 6-keto-prostaglandin F1 alpha in the umbilical artery. This suggests that ethanol inhibits phospholipase A2, but stimulates the enzymes distal from phospholipase A2 in the prostaglandin-synthesizing enzyme cascade. PMID- 3110530 TI - Arachidonic acid is involved in the regulation of hCG induced steroidogenesis in rat Leydig cells. AB - Phospholipase C (PLC), an enzyme involved in the hydrolysis of membrane phospholipid- phosphatidylinositol-bisphosphate to inositol triphosphate and diacylglycerol, and Phorbol 12, myristate 13, acetate (PMA), a tumor promoting agent, could significantly stimulate testosterone (T) secretion from Leydig cells. Arachidonic acid (AA) stimulated T secretion by about 2 fold. The steroidogenic effect of PLC and AA was biphasic. At low concentrations both PLC and AA (100 mU and 12.5 microM, respectively) augmented hCG induced T secretion, while at higher concentrations (PLC: 500 mU and AA: 200 microM) they inhibited steroid production. AA also had a biphasic effect on hCG induced cyclic AMP secretion. 5, 8, 11, 14 Eicosatetraynoic acid (ETYA), a general inhibitor of AA metabolism, and Nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway of AA metabolism, inhibited hCG induced T secretion while indomethacin, an inhibitor of cyclo-oxygenase pathway, had no effect on hCG induced T secretion. We conclude from these data that AA plays a role in the regulation of hCG induced steroidogenic responses in rat Leydig cells and that the metabolite(s) of AA that are involved are not cyclooxygenase products. PMID- 3110531 TI - Fate of 7,12-dimethylbenz(a)anthracene absorbed from the rat intestine and transported in chylomicrons. AB - Chylomicrons obtained from the thoracic duct of rats fed [3H]7,12 dimethylbenz(a)anthracene (DMBA), a polycyclic aromatic hydrocarbon, were infused intravenously into rats with bile fistulas. Over 17 hr, 55.9 +/- 3.2% (mean +/- SEM) of the radioactivity was recovered in bile and 6.7 +/- 0.5% in urine. Minor amounts were deposited in liver, kidneys and epididymal fat pads. Injection of DMBA in ethanolic solution gave a similar pattern, while biliary DMBA metabolites resulted in higher recovery in urine and lower recovery in fat. In conclusion, the major part of chylomicron DMBA is rapidly excreted via the biliary route, while a fraction is probably retained in adipose tissue. PMID- 3110532 TI - 1-Acyl-2-acetyl-sn-glycero-3-phosphocholine from stimulated human polymorphonuclear leukocytes. AB - 1-Acyl-2-acetyl-sn-glycero-3-phosphocholine (1-acyl-2-acetyl GPC) was found in the fraction of platelet-activating factor obtained from stimulated human polymorphonuclear leukocytes (PMN). The amount of 1-acyl-2-acetyl GPC obtained from 1 X 10(7) PMN stimulated with ionophore A23187 at 37 C for 15 min ranged from 8 to 56 pmol (32 +/- 10 pmol, mean +/- standard error; n = 4). The main species was 16:0 palmitoyl (17 +/- 5 pmol), followed by 18:0 stearoyl (8 +/- 3 pmol) and 18:1 oleoyl (7 +/- 3 pmol). Although the physiological significance is unknown, 1-acyl-2-acetyl GPC was always detected when 1-alkyl-2-acetyl GPC was detected. PMID- 3110533 TI - Platelet-activating factor modulates phospholipid acylation in human neutrophils. AB - The present study showed that platelet-activating factor (1-O-hexadecyl-2-acetyl sn-glycero-3-phosphocholine, PAF), but not lysoPAF (1-O-hexadecyl-sn-glycero-3 phosphocholine) rapidly (within 15 sec) stimulated the incorporation of both [1 14C]arachidonate and [1-14C]docosahexaenoate into phosphatidylinositol (PI) and phosphatidylcholine (PC) in human neutrophils. Concomitantly, it inhibited the formation of labeled phosphatidic acid from both fatty acids. The magnitude of stimulation (percentage of control) was greater in PI than in PC for the incorporation of arachidonate and vice versa for the incorporation of docosahexaenoate. It reached a maximum at 10(-7) M and started to decline at 10( 6) M. Extracellular Ca2+ was not essential for the action of PAF on phospholipid acylation. The distribution of labeled arachidonate in the molecular species of PC was not altered by PAF after 1 min incubation, suggesting that the increased formation of arachidonyl-PC during the early stage of neutrophil-PAF interaction was not originated from the added PAF. No measurable changes in the mass of each phospholipid were detected in neutrophils challenged by PAF from 15 sec to 2 min. The data suggest that the increased incorporation of extracellular fatty acids into PI and PC elicited by PAF may be secondary to increased deacylation of these phospholipids, and the magnitude of stimulation reflects the specificity of acyltransferase catalyzing the acylation of lysoPI and lysoPC by fatty acyl-CoA. PMID- 3110534 TI - Community resources for the geriatric patient. PMID- 3110535 TI - [Proportion of body constituents determined by 40K in healthy persons and in disease]. AB - Relative characteristics of the body constituents have been worked out: BCM/SMM (the amount of body cell mass per unit of the skeleton mineral mass), ELV/BCM (extracellular liquid volume per unit of the body cell mass), TBF/BCM (the amount of total body fat per BCM unit). The proposed characteristics make it possible to compare persons of various constitution, to determine a degree of deviation from normal values and to assess general function of the human body. PMID- 3110536 TI - [Principle of neutron teletherapy with the Soviet U-120 cyclotron]. AB - The authors present the results of their clinical developments on fast neutron irradiation of malignant tumors on the low-flow cyclotron U-120. The technique involved design of complexes provided with the sources of fast neutrons based on beryllium, gas deuterium and beryllium-deuterium targets. The spectrometry and dosimetry measurements of collimated bunches of fast neutrons have shown that the mean energies of neutrons from beryllium and gas deuterium targets are 6.0 and 11.5 MeV, while the absorbed doses are 0.8 and 0.5 sGy/min X microA. The increase of the local power of the biological dose inside the phantom irradiated by the collimated bunch of fast neutrons is shown to be due to intermediate energy neutrons, the contribution of which to the spectrum of fast neutrons increases with the decrease of their mean energy. The problems of selection of the sources of fast neutrons for neutron therapy are discussed. PMID- 3110537 TI - Focal motor status epilepticus following treatment with azlocillin and cefotaxime. PMID- 3110538 TI - Reproductive hormone responses to resistance exercise. AB - To investigate if changes in circulating testosterone levels during isokinetic resistance exercise in women were similar to those during intense aerobic exercise and to examine concomitant changes in hemoconcentration, specific binding protein (sex hormone binding globulin-binding capacity), non-sex hormone binding globulin bound testosterone, luteinizing hormone, follicle-stimulating hormone, cortisol, and lactate, blood samples were obtained through an indwelling cannula at 30 and 15 min before exercise, after each of six exercises on upper and lower body muscle groups, and at 15 and 30 min after exercise in seven normal menstruating women. Investigations lasting approximately 60 min were performed in the early follicular phase beginning at 3.30 p.m. after two months of training with isokinetic ("Nautilus") equipment. Baseline testosterone and non-sex hormone binding globulin bound testosterone levels were significantly higher in subjects than in a control group. Increased total and non-sex hormone binding globulin bound testosterone was observed immediately prior to exercise with further increases late in exercise, then with proportional increases in cortisol and lactic acid. Sex hormone binding globulin-binding capacity increased before exercise. The testosterone increments exceeded hemoconcentration. Luteinizing hormone and follicle-stimulating hormone levels increased during exercise. The data suggest that origins of the exercise-associated testosterone increment are complex, resulting from hemoconcentration and specific gonadal and adrenal responses. PMID- 3110539 TI - Regional differences in the replication rate of cultured rat microvascular endothelium from retroperitoneal and epididymal fat pads. AB - Study of the vascular endothelium has been greatly facilitated by the development of specific cell culture systems isolated from various tissues. We report herein a simple method for establishing a propagating cell culture system of microvascular endothelial cells derived from rat adipose tissue. In addition to the characteristic cobblestone appearance on light microscopy, the microvascular endothelial cells in culture also demonstrated the presence of other markers for large vessel endothelia. Electron microscopy revealed endothelium-specific Weibel Palade bodies and abundant pinocytotic vesicles. Both retroperitoneal and epididymal endothelia demonstrated the presence of factor VIII antigen by immunofluorescent staining and prostacyclin production. Although there was no appreciable morphological difference between cultured retroperitoneal and epididymal microvascular endothelia, the replication rate of the former was significantly higher than that of the latter (P less than .05). Excessive replication of endothelial cells may play a role in the regional differences of adipose tissue mass in an organism. PMID- 3110540 TI - Ascorbate regulation of collagen biosynthesis in Ehlers-Danlos syndrome, type VI. AB - We studied two unrelated individuals with Ehlers-Danlos syndrome type VI, which is characterized by congenital hypotonia, lax joints, severe kyphoscoliosis, friable skin, and hemorrhagic hypotrophic scars. The diagnosis was confirmed by decreased hydroxylysine residues in dermal collagen and decreased collagen lysyl hydroxylase activities in their cultured skin fibroblasts. Despite the diminished hydroxylysine residues in dermal collagen from the probands, we found no differences in hydroxylysyl residues of collagen synthesized by fibroblasts in culture. When patient 1 was given oral sodium ascorbate (5 g/d) for 3 weeks, ascorbate concentrations increased two-fold in plasma and 300-fold in urine. Urinary excretion of hydroxylysine and hydroxyproline increased during ascorbate administration. After a 1-year interval, bleeding time, wound healing, and muscle strength improved. Ascorbate supplementation (50 micrograms/mL) to confluent fibroblasts cultured from the two patients and controls increased hydroxyprolyl and hydroxylysyl residues of fibroblasts four to seven and three to four-fold respectively. Total protein associated with the cell layer increased 14% to 32% without concomitant change in cellular DNA. Total soluble collagenous material recovered from culture media increased 61% to 103% with ascorbate supplementation. These studies demonstrate that ascorbate improves the clinical status of patients with impaired collagen lysyl hydroxylase activity by enhancing lysyl and prolyl hydroxylation and total collagen production. PMID- 3110541 TI - Interactions of propionate and carnitine metabolism in isolated rat hepatocytes. AB - Accumulation of propionate and its metabolic products propionyl-CoA and methylmalonyl CoA results in disruption of normal hepatic metabolism. Carnitine can partially restore normal cellular function in the presence of propionate. This beneficial effect of carnitine has been hypothesized to result from removal of propionyl groups in the form of propionylcarnitine. The present study was designed to elucidate the kinetics of propionylcarnitine formation in isolated rat hepatocytes, and the consequences of propionylcarnitine formation on propionate and carnitine metabolism. 14C-Propionate was converted to CO2, glucose, and propionylcarnitine in the hepatocyte system. Rates of CO2 production plateaued at propionate concentrations above 0.5 to 1.0 mmol/L, while in contrast, rates of glucose production declined as the propionate concentration was increased from 1.0 to 10.0 mmol/L. Increasing concentrations of carnitine up to 10.0 mmol/L resulted in increased production of propionylcarnitine. Despite formation of propionylcarnitine, propionate conversion to CO2 and glucose was unaffected by addition of carnitine. Thus, 10 mmol/L carnitine was able to increase total propionate metabolism (conversion to CO2, glucose and propionylcarnitine) by 40%. Hepatocyte metabolism of propionate was associated with a decrease in carnitine concentration and an increase in short chain acylcarnitines. This decrease in carnitine concentration was also seen in the presence of 150 mumol/L added carnitine, and was greater with propionate as a substrate as compared to butyrate. High performance liquid chromatography was used to permit specific quantification of propionylcarnitine. This technique confirmed that in the presence of propionate, propionylcarnitine was the major acylcarnitine generated and was responsible for the depletion of free carnitine from the system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110542 TI - Immobilization of enzymes on transition metal-activated supports. PMID- 3110543 TI - Immobilization of glycoenzymes through carbohydrate chains. PMID- 3110544 TI - Entrapment of microbial cells in cellulose gel. PMID- 3110545 TI - Chemical stabilization of conformational states of dCMP deaminase. PMID- 3110546 TI - Labeling glycoconjugates with hydrazide reagents. PMID- 3110547 TI - Evonymus europaea lectin. PMID- 3110548 TI - Glycosyltransferase assay. PMID- 3110549 TI - Endo-beta-N-acetylglucosaminidase H from Streptomyces plicatus. PMID- 3110550 TI - Peptide-N4-(N-acetyl-beta-glucosaminyl) asparagine amidase and endo-beta-N acetylglucosaminidase from Flavobacterium meningosepticum. PMID- 3110551 TI - Use of lithium ion in measurement of stimulated pituitary inositol phospholipid turnover. PMID- 3110552 TI - Measurement of icosanoid precursor uptake and release by intact cells. PMID- 3110553 TI - Measurement of changes in cellular calcium metabolism in response to thyrotropin releasing hormone. PMID- 3110554 TI - Measurement of synergistic effects of protein kinase C activators and calcium ionophore in pituitary cell cultures. PMID- 3110555 TI - Mammalian monophenol monooxygenase (tyrosinase): purification, properties, and reactions catalyzed. PMID- 3110556 TI - Aromatic-L-amino acid decarboxylase. PMID- 3110558 TI - Tryptophan 5-monooxygenase from mouse mastocytoma: high-performance liquid chromatography assay. PMID- 3110557 TI - Prephenate dehydratase (monofunctional). PMID- 3110559 TI - Tryptophan 5-monooxygenase from mouse mastocytoma clone P815. PMID- 3110560 TI - Basement membranes. PMID- 3110562 TI - Dose and duration effects of oestradiol valerate on serum apolipoproteins A1 and B. AB - The serum levels of apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) were assessed by electroimmunoassay in 19 bilaterally oophorectomised women before and after treatment with 2 and 4 mg oestradiol valerate (E2V) daily. The first part of the study was conducted in accordance with an open cross-over design. The levels of ApoA1 were found to have increased after the 6-week treatment periods using each of those dosages, the increase being most pronounced after treatment with 4 mg E2V. ApoB concentrations decreased at both dosage levels. The serum levels of total (TC) and free cholesterol (FC) and phospholipids (PL) in the high density lipoprotein (HDL) fraction correlated positively with the serum levels of ApoA1 before treatment. The correlations between serum ApoA1 and HDL-PL levels persisted after both dosage regimens. Before and after treatment with 2 mg E2V, serum ApoB levels correlated positively with the levels of all lipid components in the low-density lipoprotein (LDL) fraction. After 4 mg E2V, serum ApoB levels correlated positively with LDL-PL and LDL-TC levels. On conclusion of the cross over, in order to assess the effects of the duration of therapy, the women were followed up for a further period of 3 mth, during which ten were given 2 mg and the other nine 4 mg of E2V daily. The increased levels of ApoA1 and the decreased levels of ApoB seen after the cross-over study were not found to have altered after this treatment-duration evaluation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110561 TI - Expression of heterologous genes for wall teichoic acid in Bacillus subtilis 168. AB - A localized region of low DNA sequence homology was revealed in two strains of Bacillus subtilis by a specific 100-fold reduction in transformation by W23 DNA of the tag1 locus, a teichoic acid marker of strain 168. Fifty nine rare recombinants, hybrid at this locus, had all acquired donor-specific phage resistance characters, while losing those specific to the 168 recipient. Chemical analysis of isolated cell walls showed that these modifications are associated with major changes in the wall teichoic acids. Genetic analysis demonstrated that determinants for the ribitol phosphate polymer of strain W23 had been transferred to 168, replacing those for the glycerol phosphate polymer in the recipient. All W23 genes coding for poly(ribitol phosphate) in the hybrids and those specifying anionic wall polymers in strain 168 are clustered near hisA. In addition to tag1, the region exchanged extends just beyond gtaA in some hybrids, whereas in others it may include the more distant gtaB marker, encompassing a region sufficient to contain at least 20 average-sized genes. Surface growth, flagellation, transformability and sporulation all appeared normal in hybrids examined. Recombinants without a major wall teichoic acid from either strain were not found, suggesting that an integral transfer of genes for poly(ribitol phosphate) from W23 had occurred in all hybrids isolated. We interpret these results as indicating an essential role for anionic wall polymers in the growth of B. subtilis. PMID- 3110563 TI - Endometrial effects of a continuous percutaneous oestrogen/low dose oral progestogen regimen for climacteric complaints. AB - Eleven post-menopausal women were followed up during continuous replacement therapy with percutaneous 17 beta-oestradiol, 1.5 mg, opposed by oral levo norgestrel, 30 micrograms, daily. Endometrial biopsies were taken before and after 3 months of treatment. Conventional histopathological analyses and morphometric analyses of glandular epithelial nuclei revealed only slight proliferative activity and no secretory changes. The results indicate that endometrial proliferation during post-menopausal oestrogen replacement therapy can probably be prevented by the continuous addition of a very low dose of progestogen. PMID- 3110564 TI - Influence of caffeine on mitomycin C induced mutagenesis: a simple explanation. AB - It has recently been suggested that caffeine probably represses mutations induced by mitomycin C by selectively killing cells with damaged DNA resulting from inhibition of an error-prone repair process which fails to be completed. A more likely explanation is that caffeine exerts its inhibitory effects on mitomycin C mutagenesis because of its well-documented ability to inhibit urvA.B.C-dependent excision repair. PMID- 3110565 TI - Isolation and characterization of forespores from Bacillus megaterium. AB - A procedure for isolation of intact forespores from sporulating Bacillus megaterium cells was developed. The cells were digested with lysozyme and made to release free forespores from the protoplasts by disruption of the cytoplasmic membrane with sonication in phosphate buffer containing 10% glycerol. The suitability of the procedure was confirmed by recovery of dipicolinic acid in the isolated forespores and an electron microscopic observation. The fine structure of the forespores prepared at 6 hr (t6) after initiation of sporulation was similar to that of mature spores, except that the cortex layer and primordial cell wall were thinner and the core was larger. The density, determined by density gradient centrifugation, of the forespores isolated at t6, t10, t12, and mature spores was estimated to be 1.2783, 1.2875, 1.2861, and 1.2858, respectively. The isolated forespores at t6 and t8 were extremely heat labile (D80 of 9.5 and 21.5 min, respectively) relative to mature spores (D80 of 277.8 min). These forespores were also less resistant to organic solvents. Germination of the forespores as well as mature spores was induced by KNO3, D-glucose, and L leucine. Forespores at t6 were more sensitive to KNO3-induced germination than those at t10, t12, and mature spores when measured by reduction in the optical density of cell suspension. PMID- 3110566 TI - Functional defects of culture-grown bone marrow-derived macrophages from autoimmune MRL/MpJ-lpr/lpr mice. AB - To investigate the primary defects and development of macrophages in MRL/MpJ /pr/lpr (MRL/l) mice, we used a pure population of macrophages derived from bone marrow precursor cells cultured in the presence of L-cell conditioned medium (LCM) as a source of colony stimulating factor. Bone marrow-derived macrophages (BMM phi) from MRL/l mice had lower antigen presenting activity as detected by the induction of antigen-specific T cell proliferation, than age- and sex-matched control mice (CBA/J). Cell surface antigens (Ia and Mac-1) were determined quantitatively by a cell sorter as markers of macrophage differentiation. The BMM phi from MRL/l contained a much smaller number of Ia antigen-positive macrophages than those from normal mice. Treatment of BMM phi with an Ia-inducing of factor (IFN-gamma) markedly increased the expression of Ia antigens. This increase was significantly greater in BMM phi from MRL/l mice than in BMM phi from control mice. Expression of Mac-1 antigen was not different in BMM phi from the two strains. The Fc-mediated phagocytosis of IgG-coated sheep red blood cells was decreased in BMM phi from MRL/l mice compared with those from control mice. The function of nonspecific phagocytosis as measured by latex-bead incorporation was also impaired in MRL/l mice. The functional defects of MRL/l BMM phi found in these experiments are not secondary defects acquired under the influence of environmental signals during development, but are derived from the primary abnormalities which already exist in myeloid stem cells. PMID- 3110567 TI - [Feasibility of the combined use of the chemosterilizing agent dimatiph and the growth inhibitor dimilin to control flies in cattle-rasing brans]. PMID- 3110568 TI - Measles prevention. PMID- 3110569 TI - Protective effect of physical activity on coronary heart disease. PMID- 3110570 TI - Use of seat belts--DeKalb County, Georgia, 1986. PMID- 3110571 TI - Underreporting of alcohol-related mortality on death certificates of young U.S. Army veterans. PMID- 3110572 TI - Multistate outbreak of Shigella sonnei gastroenteritis--United States. PMID- 3110574 TI - Arboviral infections of the central nervous system--United States, 1986. PMID- 3110575 TI - Rubella vaccination during pregnancy--United States, 1971-1986. PMID- 3110573 TI - Shigellosis--North Carolina. PMID- 3110576 TI - Traumatic occupational fatalities--United States, 1980-1984. PMID- 3110578 TI - Tetanus--United States, 1985-1986. PMID- 3110577 TI - Serum dioxin in Vietnam-era veterans--preliminary report. PMID- 3110579 TI - Thallium poisoning: an epidemic of false positives--Georgetown, Guyana. PMID- 3110580 TI - Tertiary syphilis deaths--South Florida. PMID- 3110581 TI - Tuberculosis among American Indians and Alaskan natives--United States, 1985. PMID- 3110582 TI - Mumps outbreaks on university campuses--Illinois, Wisconsin, South Dakota. PMID- 3110583 TI - Reduction of children's arsenic exposure following relocation--Mill Creek, Montana. PMID- 3110584 TI - Teenage pregnancy and fertility in the United States, 1970, 1974, and 1980. PMID- 3110585 TI - Abortion surveillance, 1982-1983. PMID- 3110586 TI - Sudden unexplained death syndrome in Southeast Asian refugees: a review of CDC surveillance. PMID- 3110587 TI - [Experimental study of the effect of an elemental diet on liver regeneration]. AB - The influence of branched chain amino acids and lipid on liver regeneration was examined after two-thirds hepatectomy in rats. Elemental diet (ED) as components of enteral nutrition was given through the gastrostomy tube. The rats were divided into four groups according to the amounts of branched chain amino acids (BCAA) and lipid in the diet as follows: ED-I; BCAA 27%, Cal/N ratio: 74, ED-II; BCAA 37%, Cal/N ratio: 95, ED-III; BCAA 37% + lipid emulsion, Cal/N ratio: 99, ED AC; commercially available elemental diet. The degree of liver regeneration of these groups of rats were compared with that of the control rats which were fed per os ad libitum. The liver regeneration rate of each group was as follows: ED I; 59%, ED-II; 88%, ED-III; 92%, ED-AC; 79%, the control group; 89%. Remarkable fatty deposits were microscopically observed in each liver of ED-I, II and AC groups. Fatty change in the liver of ED-III group was minimum. The observation indicates that administration of branched chain amino acid enriched elemental diet and lipid emulsion is effective for regeneration of the liver after partial hepatectomy. PMID- 3110588 TI - [Immunohistochemical study of the regional lymph nodes in gastric cancer]. AB - Immunohistochemical study with various monoclonal antibodies against the mononuclear cell surface antigen was performed on the regional lymph nodes of gastric cancer through Avidin-Biotin Complex (ABC) method. In the paracortical area (P.C.) of those lymph nodes without the metastasis of gastric cancer, T cells were dominant, and OKT3 positive (OKT3+) cells and OKT4+ cells were diffusely present, while OKT8+ cells were occasionally recognized. In the sinus, subsets of the above T cells, and OKT9+ cells and OKT10+ cells were observed. In the germinal center (G.C.), mantle zone (M.Z.) and primary follicle (P.F.), which were B cell regions, OKIa1+ cells and Leu12+ cells were diffusely present. OKB7+ cells, OKT9+ cells, OKT10+ cells and Leu7+ cells were also noted in G.C.. Leu8+ cells were observed in M.Z. and P.F.. OKIa1+ cells were occasionally noted in P.C. and sinus. In the lymph nodes with the metastasis, decrease of OKT4+ cells and increase of OKT8+ cells were noted in comparison to the lymph nodes without the metastasis. Using the tissue double fluorescence staining method, it was found that about half of the OKT4+ cells were helper T cells. The majority of OKT8+ cells were identified as cytotoxic T cells or their precursors. By preoperative endoscopic administration of OK-432 or PSK into the tumor, the IL-2 receptor+ cells, or OKM1+ cells and OKT4+ cells increased in the regional lymph nodes and the antitumor activity was intensified. PMID- 3110589 TI - Defective induction of phenol glucuronidation by 3-methylcholanthrene in Gunn rats is due to the absence of a specific UDP-glucuronosyltransferase isoenzyme. AB - Antiserum directed against purified rat kidney UDP-glucuronosyltransferase (UDPGT) was raised in goats. IgG prepared from this antiserum exhibited specificity for only two UDPGT isoenzymes (bilirubin and phenol) on immunoblot analysis of Wistar rat liver microsomes. Use of this antibody preparation to probe Western blots of liver microsomes prepared from Gunn rats confirmed that the defective phenol glucuronidation was due to the absence of a 53-kDa, 3 methylcholanthrene-inducible UDPGT isoenzyme. Results obtained from enzyme activity measurements and immunoblot analysis of microsomes isolated from xenobiotic-treated Wistar and Gunn rat liver are consistent with the 3 methylcholanthrene/UDPGT induction deficiency in the Gunn rat being due to the absence of this phenol UDPGT isoenzyme. The contribution of other UDPGT isoenzymes to the greatly reduced glucuronidation of planar phenols observed in the Gunn rat is discussed. PMID- 3110591 TI - Structural characteristics of the 35- and 36-kDa forms of the beta subunit common to GTP-binding regulatory proteins. AB - The beta subunit common to GTP-binding regulatory proteins can be resolved into immunologically distinct proteins typically referred to as 35- and 36-kDa forms of the subunit. The extent to which these two forms are structurally related was examined by isoelectric focusing, nonequilibrium pH gradient electrophoresis (NEPHGE), and two-dimensional peptide mapping. Each of the two forms of the beta subunit isolated from rabbit liver was found to comprise species of protein having isoelectric points of 5.7, 5.8, and 5.95; those having an isoelectric point of 5.8 were the most prominent. The beta subunits isolated from bovine brain and rod outer segments exhibited species having identical isoelectric points. Similar patterns of species were also noted for forms of the beta subunit detected immunologically within diverse types of cells. Analysis of the 35- and 36-kDa forms of the beta subunit by NEPHGE confirmed the absence, with only minor exceptions, of other constituent proteins. Subjection of chymotryptic peptides to high voltage electrophoresis and chromatography on cellulose revealed similarities, as well as differences, between the two forms of the beta subunit. These data provide evidence that the 35- and 36-kDa forms of the beta subunit are indeed structurally related and are conserved among diverse types of cells. PMID- 3110590 TI - Stimulation of biliary glutathione secretion by sulfonylureas. AB - In isolated perfused rat livers, infusion of the sulfonylureas, glyburide (2.5 microM) and tolbutamide (0.5 mM), stimulated by 2-fold the rate of biliary glutathione secretion. This increase was mainly the result of an apparent increase in the rate of reduced glutathione release by the liver since oxidized glutathione levels in the bile remained unchanged. Sulfonylurea infusion into perfused livers did not alter the rate of glutathione release in the perfusate, indicating that sinusoidal release was not perturbed. N-Benzylimidazole (0.2 mM), an inhibitor of cytochrome P-450, blocked the tolbutamide-mediated increase in biliary release of glutathione. However, the cytochrome P-450 inhibitor did not alter the glyburide-induced increase in biliary glutathione secretion. Glyburide infusion into perfused livers also decreased tissue oxidized glutathione content without altering the total tissue levels of glutathione. The stimulation of biliary glutathione release by sulfonylureas is probably the result of excretion of labile conjugates of glutathione and sulfonylurea metabolites. Although the precise identity of these metabolites is presently unknown, formyltolbutamide and hydroxyglyburide formed during metabolism of tolbutamide and glyburide, respectively, may be the prime candidates for forming labile glutathione conjugates. PMID- 3110592 TI - Regioselectivity of rat liver microsomal UDP-glucuronosyltransferase activities toward phenols of benzo(a)pyrene and dibenz(a,h)anthracene. AB - Inducibility of rat liver microsomal UDP-glucuronosyltransferase was investigated with regard to the substrate structure using 3-, 6-, 7-, 8-, and 9 hydroxybenzo(a)pyrene, all seven phenols of dibenz(a,h)anthracene, 3 hydroxybenz(a)anthracene, and 3-hydroxyfluoranthene as substrates. Glucuronide formation of the majority of the planar phenols was preferentially inducible by 3 methylcholanthrene (4- to 8-fold, group 1). However, glucuronidation of 8 hydroxybenzo(a)pyrene, 3-hydroxybenz(a)anthracene, and 3 hydroxydibenz(a,h)anthracene was markedly inducible by phenobarbital (3- to 8 fold, group 2). Glucuronidation of 9-hydroxybenzo(a)pyrene and 3 hydroxyfluoranthene was only moderately induced by the two inducers (less than 2 fold, group 3). Glucuronidation was also determined with purified phenol UDP glucuronosyltransferase from 3-methylcholanthrene-treated rats. A close correlation (r = 0.95) was observed between purification factors (ratio of enzyme activities in purified enzyme and microsomes) and induction factors (ratio of microsomal enzyme activities from 3-methylcholanthrene-treated rats and untreated controls). Interestingly, differences in size and shape of group 1 and 2 substrates could be recognized. Group 1 substrates were shorter (less than 1.3 nm) and broader (greater than 1.1 nm) than group 2 substrates when viewed from the hydroxy group, along the axis of the C-O bond, to the plane of the polycyclic aromatic hydrocarbon, suggesting a distinct geometry of the binding site of the 3 methylcholanthrene-inducible phenol UDP-glucuronosyltransferase. PMID- 3110593 TI - Nonmitogenic morphoregulatory action of pp60v-src on multicellular epithelial structures. AB - Madin-Darby canine kidney (MDCK) cells form polarized, multicellular epithelial structures in vitro. Low-level expression of pp60v-src in MDCK cells elicits plasticity in these multicellular structures. Plasticity was revealed by the displacement of cells from mechanically stressed regions of the epithelial monolayers; however, the two-dimensional relationship between the cells in the remainder of the monolayer was maintained. Electron microscopy of multicellular structures revealed abnormal separation of the lateral membranes of adjacent cells and selective uncoupling of the junctional complex; the zonula adherens was disrupted, but the zonula occludens and desmosomes were retained. Significantly, this result was not accompanied by transformation of the cells, as judged by the absence of anchorage-independent growth potential. These results demonstrate a nonmitogenic biological activity of pp60v-src which is experimentally dissociable from transformation. This morphoregulatory action on higher-order epithelial structures may reflect a function of related cellular tyrosine kinases. PMID- 3110594 TI - In vitro splicing of kappa immunoglobulin precursor mRNA. AB - The in vitro splicing of kappa immunoglobulin precursor mRNA was studied as an example of a naturally occurring mRNA possessing multiple 5' splice sites. Several kappa mRNAs were generated in vitro by using an SP6 transcription system and were spliced in nuclear extracts derived from HeLa cells. Products and intermediates resulting from in vitro splicing were identified and characterized. In contrast to the in vivo situation, in which apparently only the 5'-most splice donor site is used, all of the 5' splice sites were used in vitro with equal frequency. Neither the presence or absence of variable region coding sequences nor the deletion of intron sequences had an effect on in vitro splice site selection. PMID- 3110596 TI - Cloning, sequence determination, and expression in transfected cells of the coding sequence for the tox 176 attenuated diphtheria toxin A chain. AB - DNA including the coding sequence for the A chain of the mutant diphtheria toxin tox 176 was cloned. The cloned mature A-chain coding sequence showed a G-to-A transition at nucleotide 383 as the only difference from the wild-type sequence. This resulted in replacement of the glycine at position 128 by aspartic acid in the predicted amino acid sequence. A eucaryotic cell expression plasmid, pTH1 176, was constructed in which the tox 176 A-chain coding sequence was attached to a truncated metallothionein promoter. The toxicity of this construct, compared with that of the corresponding wild-type diphtheria toxin A-chain plasmid, pTH1, was assessed after transfection into the human 293 cell line by an indirect transient expression assay (I. H. Maxwell, F. Maxwell, and L. M. Glode, Cancer Res. 46:4660-4664, 1986). For the same effect, 15- to 30-fold more pTH1-176 than pTH1 was required, a result consistent with previous in vitro estimates of the diminished activity of the tox 176 A chain. Controlled expression of the cloned tox 176 A-chain coding sequence may provide a means of eliminating specific cell populations in an organism, for which purpose the wild-type diphtheria toxin A chain might prove too toxic. PMID- 3110595 TI - Inactivation of a transfected gene in human fibroblasts can occur by deletion, amplification, phenotypic switching, or methylation. AB - Plasmids containing the bacterial gpt gene under control of the simian virus 40 promoter were transfected into a simian virus 40-transformed human fibroblast line. Two transfectants, E2 and C10, which contain stably integrated single copies of the gpt gene, were isolated. These two lines produce Gpt- variants spontaneously with a frequency of about 10(-4). We carried out a detailed molecular analysis of the spectrum of alterations which gave rise to the Gpt- phenotype in these variants. DNA from 14 of 19 Gpt- derivatives of one of the cell lines (E2) contains deletions or rearrangements of gpt-containing sequences. In four of the remaining five lines, the Gpt- phenotype was correlated with reduced levels of expression rather than with changes in the gross structure of the gpt gene, and it was possible to reactivate the gpt gene. In one Gpt- line, gpt mRNA was present at normal levels, but no active enzyme was produced. Spontaneous Gpt- derivatives of the other cell line (C10) produced a completely different spectrum of alterations. Very few deletions were found, but several derivatives contained additional extrachromosomal gpt sequences, and, remarkably, in two other Gpt- lines, gpt-containing sequences were amplified more than 100 fold. The phenotypes of the majority of the Gpt- derivatives of C10 could be attributed to alterations in gene expression caused by methylation. PMID- 3110597 TI - A DNA segment controlling metal-regulated expression of the Drosophila melanogaster metallothionein gene Mtn. AB - Cloned fragments of DNA including the Drosophila melanogaster metallothionein gene Mtn and different amounts of 5' flanking sequences were introduced into flies by P-element-mediated germ line transformation. Comparison of RNA levels in different transformants revealed that metal-regulated and tissue-specific expression of Mtn requires no more than 373 base pairs upstream of the initiation site of transcription. Transformants having an additional, transcribed copy of Mtn could tolerate increased concentrations of cadmium, indicating that Mtn expression is directly related to this phenotype. In separate experiments, these D. melanogaster promoter sequences were fused to the coding sequences of the herpes simplex virus thymidine kinase (TK) gene. After transfection of this fusion into baby hamster kidney cells, increases in TK activity and accumulation of TK RNA were inducible by metals. A series of 5' and 3' deletions showed that D. melanogaster sequences from -130 to -6 were sufficient to confer metal regulated expression to the TK gene. The function of the D. melanogaster metallothionein promoter in mammalian cells indicates that the mechanism controlling metal regulation is evolutionarily conserved. PMID- 3110598 TI - Primary structure of human nuclear ribonucleoprotein particle C proteins: conservation of sequence and domain structures in heterogeneous nuclear RNA, mRNA, and pre-rRNA-binding proteins. AB - In the eucaryotic nucleus, heterogeneous nuclear RNAs exist in a complex with a specific set of proteins to form heterogeneous nuclear ribonucleoprotein particles (hnRNPs). The C proteins, C1 and C2, are major constituents of hnRNPs and appear to play a role in RNA splicing as suggested by antibody inhibition and immunodepletion experiments. With the use of a previously described partial cDNA clone as a hybridization probe, full-length cDNAs for the human C proteins were isolated. All of the cDNAs isolated hybridized to two poly(A)+ RNAs of 1.9 and 1.4 kilobases (kb). DNA sequencing of a cDNA clone for the 1.9-kb mRNA (pHC12) revealed a single open reading frame of 290 amino acids coding for a protein of 31,931 daltons and two polyadenylation signals, AAUAAA, approximately 400 base pairs apart in the 3' untranslated region of the mRNA. DNA sequencing of a clone corresponding to the 1.4-kb mRNA (pHC5) indicated that the sequence of this mRNA is identical to that of the 1.9-kb mRNA up to the first polyadenylation signal which it uses. Both mRNAs therefore have the same coding capacity and are probably transcribed from a single gene. Translation in vitro of the 1.9-kb mRNA selected by hybridization with a 3'-end subfragment of pHC12 demonstrated that it by itself can direct the synthesis of both C1 and C2. The difference between the C1 and C2 proteins which results in their electrophoretic separation is not known, but most likely one of them is generated from the other posttranslationally. Since several hnRNP proteins appeared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis as multiple antigenically related polypeptides, this raises the possibility that some of these other groups of hnRNP proteins are also each produced from a single mRNA. The predicted amino acid sequence of the protein indicates that it is composed of two distinct domains: an amino terminus that contains what we have recently described as a RNP consensus sequence, which is the putative RNA-binding site, and a carboxy terminus that is very negatively charged, contains no aromatic amino acids or prolines, and contains a putative nucleoside triphosphate-binding fold, as well as a phosphorylation site for casein kinase type II. The RNP consensus sequence was also found in the yeast poly(A)-binding protein (PABP), the heterogeneous nuclear RNA-binding proteins A1 and A2, and the pre-rRNA binding protein C23. All of these proteins are also composed of at least two distinct domains: an amino terminus, which possesses one or more RNP consensus sequences, and a carboxy terminus, which is unique to each protein, being very acidic in the C proteins and rich in glycine in A1, and C23 and rich in proline in the poly(A)-binding protein. These findings suggest that the amino terminus of these proteins possesses a highly conserved RNA-binding domain, whereas the carboxy terminus contains a region essential to the unique function and interactions of each of the RNA-binding proteins. PMID- 3110599 TI - In vitro transcription of immunoglobulin genes in a B-cell extract: effects of enhancer and promoter sequences. AB - Transfection experiments have led to the identification of three DNA sequences that are responsible for the tissue-specific expression of immunoglobulin genes. As a first step toward characterizing these regulatory phenomena at the biochemical level, we report the development of an in vitro transcription system from cells of the B lymphoid lineage. In these extracts, transcription of the MOPC41 kappa promoter is correctly initiated and dependent on the presence of an upstream sequence element located between -44 and -79 base pairs from the cap site. Second, although standard in vitro transcriptions are not affected by the presence or absence of enhancer sequences, we observed that the addition of polyethylene glycol led to a B-cell extract-specific suppression of transcription from a template that carries an immunoglobulin enhancer. PMID- 3110600 TI - Generation of a variant t(2;8) translocation of Burkitt's lymphoma by site specific recombination via the kappa light-chain joining signals. AB - We analyzed the Burkitt's lymphoma line BL64 in which a reciprocal translocation joins the immunoglobulin kappa light-chain locus on chromosome 2 to the c-myc gene on chromosome 8. The breakpoints on the two marker chromosomes 8+ and 2p- occurred 5' of the Js segment within the conserved nonamer and heptamer recombination sequences. Both signals were detected directly adjacent to the breakpoints in sequences of chromosome 8 suggesting that the translocation in BL64 was catalyzed by enzymes normally involved in V-J recombination. The distance between the c-myc gene and the breakpoint in J kappa amounts to at least 90 kilobases on the DNA level. In one allele of the c-myc gene somatic mutations were found in the promoter-leader region. This allele is transcribed and is supposed to be involved in the translocation. The half-life of the c-myc-specific mRNA in BL64 cells is not prolonged in comparison to the normal c-myc message. These results suggest that in Burkitt's lymphoma the translocation occurs during an early stage of B-cell differentiation and that in the variant translocations mechanisms other than a prolonged half-life, such as changes in transcriptional rates, or other posttranscriptional RNA processing contribute to the high steady state level of c-myc RNA in the cytoplasm. PMID- 3110601 TI - Formation of an active transcription complex in the Drosophila melanogaster 5S RNA gene is dependent on an upstream region. AB - We constructed deletion-substitution and linker-scanning mutations in the 5' flanking region of the Drosophila melanogaster 5S RNA gene. In vitro transcription of these templates in Drosophila and HeLa cell extracts revealed the presence of an essential control region (-30 region) located between nucleotides -39 and -26 upstream of the transcription initiation site: deletion of sequences upstream of nucleotide position -39 had no detectable effect on the wild-type level of in vitro transcription, whereas mutations extending between positions -39 and 1 resulted in templates with decreased transcriptional levels; specifically, deletion and linker-scanning mutations in the -34 to -26 region ( 30 region) resulted in loss of transcription. The -30 region is essential for transcription and therefore forms part of the Drosophila 5S RNA gene transcription promoter. Compared with the activity of the wild-type gene, mutant 5S DNAs exhibited no impairment in the ability to sequester limiting transcription factors in a template exclusion competition assay. While we do not know which transcription factor(s) interacts with the -30 region, the possible involvement of RNA polymerase III at this region is discussed. PMID- 3110604 TI - Polychlorinated biphenyls: a brief review. PMID- 3110602 TI - Primary sequence and developmental expression of a novel Drosophila melanogaster src gene. AB - We have sequenced a cDNA clone for the Drosophila melanogaster gene Dsrc28C, a homolog of the vertebrate gene c-src. The cDNA contains a single open reading frame encoding a protein of 66 kilodaltons which contains features highly conserved within the src family of tyrosine protein kinases. Novel structural features of the Dsrc28C protein include a basic pI and a polyglycine domain near the amino terminus. Cell-free translation of in vitro-transcribed RNA yielded a protein of the predicted size which could be immunoprecipitated by anti-v-src antisera. RNA blot hybridization revealed that the gene is expressed predominantly during embryogenesis, in imaginal disks of third-instar larvae, and in adult females. In situ hybridization showed that expression in adult females is largely confined to nurse cells and developing oocytes. PMID- 3110605 TI - [The bounds of the riboflavin operon in Bacillus subtilis]. AB - All the structural genes of riboflavin biosynthesis are shown to be located on the 2.8 MD DNA fragment, using the collection of plasmids, carrying the Bacillus subtilis riboflavin operon fragments and Bacillus subtilis strains, containing various deletions of rib-operon for analysis. The proximal Bgl II site is shown to be located between promoter P1 and the first structural gene ribG. The distal Hind III site of fragment C is the left bound of the rib-operon. PMID- 3110603 TI - Modification of fos proteins: phosphorylation of c-fos, but not v-fos, is stimulated by 12-tetradecanoyl-phorbol-13-acetate and serum. AB - We have investigated the covalent modification of the proteins encoded by the murine fos proto-oncogene (c-fos) and that of the corresponding gene product of FBJ murine osteosarcoma virus (v-fos). Both proteins are posttranslationally processed in the cell, resulting in forms with lower electrophoretic mobilities than that of the initial translation product on sodium dodecyl sulfate polyacrylamide gels. Treatment with alkaline phosphatase indicates that most, if not all, of this electrophoretic shift is due to phosphoesterification of both proteins. These phosphoryl groups stoichiometrically modify the v-fos and c-fos proteins on serine residues and turn over rapidly in vivo in the presence of protein kinase inhibitors (half-life, less than 15 min). Direct quantitative comparison of steady-state labeling studies with L-[35S]methionine and [32P]phosphate reveals that the c-fos protein is four- to fivefold more highly phosphorylated than the v-fos protein is. Comparison of tryptic fragments from [32P]phosphate-labeled proteins indicates that although the two proteins have several tryptic phosphopeptides in common, the c-fos protein contains unique major tryptic phosphopeptides that the v-fos protein lacks. These unique sites of c-fos phosphorylation have been tentatively localized to the carboxy-terminal 20 amino acid residues of the protein. Phosphorylation of the c-fos protein, but not the v-fos protein, can be stimulated at least fivefold in vivo by the addition of either 12-tetradecanoyl-phorbol-13-acetate or serum. This increase in the steady state degree of phosphorylation of c-fos appears to be independent of protein kinase C since phosphorylation is Ca2+ and diacylglycerol independent. The possible role of phosphorylation of these proteins in cellular transformation is discussed. PMID- 3110606 TI - [Structural-functional characteristics of Bacillus mesentericus promoters cloned in Bacillus subtilis cells]. AB - Bacillus mesentericus DNA fragments carrying promoters were cloned in Bacillus subtilis. The nucleotide sequences of four promoters, the sites of transcription initiation and the levels of promoter-mediated expression of pPL603 CAT gene at different stages of cell growth were determined. It was identified, that the two promoters (P435 and P442) are the typical sigma 43-RNA polymerase promoters. Promoter P462 possessed the unusual nucleotide sequence and induced the expression of indicator CAT gene at the middle of the stationary phase of cell growth. The next P428 promoter was found to be a complex promoter composed of three overlapping ones: P428-1, P428-2 and P428-3. P428-3 is the sigma 43 specific promoter which revealed the high degree of homology with Bacillus subtilis spoOB gene promoter. We suggest the promoters P428-1 and P428-2 to be sigma 43- and sigma 37-RNA polymerase specific, respectively. PMID- 3110607 TI - Retinol (vitamin A) inhibits the mutagenicity of o-aminoazotoluene activated by liver microsomes from several species in the Ames test. AB - Retinol (vitamin A) has earlier been shown to inhibit the mutagenicity of o aminoazotoluene (OAAT) in the Salmonella/microsome assay when OAAT is activated with S9 from Sprague-Dawley rats. The results presented in this paper confirm this and also show that S9 from mice, hamsters and gerbils activates OAAT to mutagenic metabolites detected by Salmonella typhimurium TA100. However, S9 from rabbits is inactive. The S9 fraction from rabbits also shows a low aryl hydrocarbon hydroxylase (AHH) activity. The AHH activity or protein content of the microsomal fraction cannot be used to predict the activating capacity of S9 from the other species. Retinol, added in vitro, inhibits the mutagenic effect of OAAT activated by mouse, gerbil or hamster S9. The strongest inhibition is observed with hamster S9 while the inhibition of mouse and gerbil S9 is lower but still higher than in the rat. PMID- 3110608 TI - 32P-analysis of DNA adducts in somatic and reproductive tissues of rats treated with the anticancer antibiotic, mitomycin C. AB - Mitomycin C (MMC) is a clinically used drug with mutagenic and antitumor activities, presumably elicited through its covalent binding to DNA, however, little is known about MMC binding to DNA in vivo. A 32P-postlabeling method that does not require radiolabeled test compounds was employed here to study the formation of DNA adducts in somatic and reproductive tissues of rats 24 h after an i.p. dose of 9 mg/kg MMC. Among 14 tissues studied in female rats, MMC-DNA adduct levels were within a 2-fold range in 11 tissues, i.e. bladder, colon, esophagus, heart, kidney, liver, lung, ovary, pancreas, small intestine and stomach (minimum levels of 9.6-21.9 adducts per 10(7) N). Three other tissues, i.e. brain, spleen and thymus, exhibited lower adduct levels (0.2 5.4 and 1.4 adducts, respectively, per 10(7) N). Liver DNA adduct levels were 32% lower in male than in female rats. Testicular DNA contained 2.5 adducts per 10(7) N, i.e. 5.3 times less than ovarian DNA. 32P-labeled adduct patterns were qualitatively similar among the different tissues and consisted of 10 adducts, one of which comprised 71 (+/- 5)% of the total. All these adducts were chromatographically identical to adducts formed by the reaction of chemically reduced MMC with DNA in vitro, demonstrating that metabolic activation of MMC occurred via reduction. Using homopolydeoxyribonucleotides modified with MMC, in vivo adducts were shown to be mostly (greater than 90%) guanine derivatives and small amounts of adenine, cytosine and thymine products. Most of the adducts appeared to be monofunctional derivatives of DNA nucleotides. Dose-dependent MMC-DNA adduct formation was determined in rat liver over an 82-fold range of MMC administered (0.11-9.0 mg/kg). The lowest dose level studied was 4.5 times lower than the recommended single dose for human cancer chemotherapy (20 mg/m2). Thus, these results predict that 32P-postlabeling methodology is suitable to monitor and quantify DNA adducts in tissue biopsies of patients receiving MMC chemotherapy. PMID- 3110609 TI - DNA replication-blocking properties of adducts formed by aflatoxin B1-2,3 dichloride and aflatoxin B1-2,3-oxide. AB - The carcinogen aflatoxin B1 (AFB1), upon activation to a hypothesized AFB1-2,3 oxide (AFB1-oxide), reacts with DNA guanines. Aflatoxin B1-2,3-dichloride (AFB1 Cl2) was originally synthesized as an electronic analog for the putative AFB1 oxide, which has never been isolated due to presumed reactivity. We have previously shown that AFB1-oxide reacts with base-paired DNA guanines in a sequence-specific manner, as revealed by an alkali-degradation analysis. On the basis of a replication-block analysis, we have shown that AFB1-Cl2 reacts with single-stranded DNA preferentially at inverted repeat sequences, which were suggested to be capable of forming intrastrand base-paired structures. Here, we present data to show the following. Both AFB1-oxide and AFB1-Cl2 react with guanines in double-stranded DNA to induce similar sequence-specific, alkali labile sites. Reactivity with partial DNA duplexes as well as the use of single strand specific chemical probes directly demonstrates that AFB1-Cl2, like AFB1 oxide, prefers base-paired guanines over non-base-paired guanines. DNA replication block patterns induced by AFB1-oxide are essentially similar to those induced by AFB1-Cl2. Unexpectedly, and unlike other tested DNA lesions, Mn2+ does not appear to affect the template blocking properties of the adduct formed by AFB1-Cl2 or AFB1-oxide. The sites for replication stoppage as well as the lack of a Mn2+ effect on adducted templates have implications for the mechanisms of mutagenesis by activated AFB1. PMID- 3110610 TI - Induction of umu gene expression by cross-links and other DNA lesions. AB - The induction of umu gene expression by DNA cross-links was investigated in various strains of E. coli with different DNA-repair capacities. Expression was measured by quantifying enzymatic activity of beta-galactosidase produced under regulation of the umu promoter carried on a plasmid carrying the umuC-lacZ gene fusion. The treatment with MMC induced gene expression more efficiently in a wild type strain when compared with an excision-repair-deficient strain (uvrA). In contrast, PUVA and cis-Pt treatment induced higher levels of the gene expression in the uvrA strain than in the wild-type strain, as did other DNA-damaging agents including 4NQO, MNNG and MMS. None of these chemicals induced umu expression in either lexA and recA strains. The mechanisms of the induction of umu expression by DNA cross-links in relation to DNA damage and repair are discussed. PMID- 3110611 TI - Investigations on DNA binding in rat liver and in Salmonella and on mutagenicity in the Ames test by emodin, a natural anthraquinone. AB - Emodin (1,6,8-trihydroxy-3-methylanthraquinone), an important aglycone found in natural anthraquinone glycosides frequently used in laxative drugs, was mutagenic in the Salmonella/mammalian microsome assay (Ames test) with a specificity for strain TA1537. The mutagenic activity was activation-dependent with an optimal amount of S9 from Aroclor 1254-treated male Sprague-Dawley rats of 20% in the S9 mix (v/v) for 10 micrograms emodin per plate. Heat inactivation of the S9 for 30 min at 60 degrees C prevented mutagenicity. The addition of the cytochrome P-448 inhibitor 7,8-benzoflavone (18.5 nmoles per plate) reduced the mutagenic activity of 5.0 micrograms emodin per plate to about one third, whereas the P-450 inhibitor metyrapone (up to 1850 nmoles per plate) was without effect. To test whether a metabolite binds covalently to Salmonella DNA, [10-(14)C]emodin was radiosynthesized, large batches of bacteria were incubated with [10-(14)C]emodin and DNA was isolated. [G-3H]Aflatoxin B1 (AFB1) was used as a positive control mutagen known to act via DNA binding. DNA obtained after aflatoxin treatment could be purified to constant specific activity. With emodin, the specific activity of DNA did not remain constant after repeated precipitations so that it is unlikely that the mutagenicity of emodin is due to covalent interaction of a metabolite with DNA. The antioxidants vitamin C and E or glutathione did not reduce the mutagenicity. Emodin was also negative with strain TA102. Thus, oxygen radicals are probably not involved. When emodin was incubated with S9 alone for up to 50 h before heat-inactivation of the enzymes and addition of bacteria, the mutagenic activity did not decrease. It is concluded that the mutagenicity of emodin is due to a chemically stable, oxidized metabolite forming physico chemical associations with DNA, possibly of the intercalative type. In order to check whether an intact mammalian organism might be able to activate emodin to a DNA-binding metabolite, radiolabelled emodin was administered by oral gavage to male SD rats and liver DNA was isolated after 72 h. Very little radioactivity was associated with the DNA. Considering that DNA radioactivity could also be due to sources other than covalent interactions, an upper limit for the covalent binding index, CBI = (mumoles chemical bound per moles DNA nucleotides)/(mmoles chemical administered per kg body weight) of 0.5 is deduced. This is 10(4) times below the CBI of AFB1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3110612 TI - Mutagenicity testing of the juvenoid methoprene (ZR-515) by means of the Drosophila wing spot test. AB - The juvenile hormone analogue methoprene, which is used in insect pest control, was subjected to mutagenicity testing by means of the Drosophila wing spot test. Larvae heterozygous for recessive wing trichome mutations were exposed to a sublethal dose of methoprene. Wings of emerged adult females were inspected for the presence of phenotypically mutant mosaic spots. Methoprene exhibited a weak mutagenic effect. The fact that only small mosaic clones were induced is discussed. PMID- 3110613 TI - The effect of dietary imbalances on the activation of benzo[a]pyrene by the metabolizing enzymes from rat liver. AB - Male Sprague-Dawley rats (70-80 g) were fed ad libitum a standard control diet (22% casein, 5% lard), or a high lipid diet (30% lard) or a low protein diet (6% casein) or a standard diet containing 50 ppm phenoclor DP6. After 6 weeks on these diets, the cytochrome P-450 microsomal content, the benzo[a]pyrene monooxygenase (BaP-MO) and the epoxide hydrolase (EH) were assayed. The formation of mutagenic B(a)P metabolites which covalently bind with DNA was compared. The activity of BaP-MO and of EH were increased by the high lipid diet (+27% and 106% respectively) and by the phenoclor DP6 treatment (+63% and 400% respectively), compared to the standard diet. In animals fed a low protein diet the BaP-MO was decreased (-34%) and the EH activity was strongly increased (+262%) compared to those fed a standard diet. All experimental diets increased both the activation of BaP to metabolites able to bind DNA and the mutagenicity of BaP versus TA98 Salmonella typhimurium strain. It was concluded that dietary imbalances can be considered as a factor in chemical carcinogenesis. PMID- 3110614 TI - Dinitrofluoranthene: induction, identification and gene mutation. AB - By renitrating 3-nitrofluoranthene in the presence of fuming nitric acid, some additional nitro-derivatives were induced; they were identified as 3,7-, 3,9- and 3,4-dinitrofluoranthene (DNF), and two trinitrofluoranthenes (TNF, 3,4,7- and 3,4,8- or 3,4,9-isomers) on the basis of the results of mass spectrometry and 1H nuclear magnetic resonance. The yield of 3,7- and 3,9-DNF was about 61.3% in all of the derivatives induced. All of the DNFs yielded positive results in the rec assay system, inducing DNA-damaging activity in Bacillus subtilis. Both 3,7- and 3,9-DNF converted Salmonella typhimurium His- strains TA98, TA97 and TA1538 from autotrophy to prototrophy, indicating a frameshift-type mutation for both; for strain TA98, 3,7-, 3,9- and 3,4-DNF gave mutagenicity of 422, 355 and 15.5 His+ revertants, respectively, per nanogram, corresponding to the specific activity of 1,6-dinitropyrene (DNP), a powerful mutagen. These DNFs are known to be potential mutagens which are eluted at adjacent retention times with 1,3-, 1,6- and 1,8-DNP on a column for high-performance liquid chromatography. PMID- 3110615 TI - Effects of benzamide pretreatment on clastogenic adaptation of Vicia faba root tip meristem cells to triethylenemelamine (TEM) and maleic hydrazide (MH). AB - Clastogenic adaptation to TEM or MH no longer occurred when benzamide, an inhibitor of nuclear ADP-ribosyltransferase (ADPRT), was applied prior to the low dose (conditioning) treatment which triggers this phenomenon. This may be indicative that inducible processes connected with ribosylation reactions are involved in the protective effects exerted by clastogenic adaptation. No increase by benzamide pretreatment was observed in the yield of metaphases with TEM- or MH induced chromatid aberrations after conditioning and challenge treatment, respectively. High benzamide concentrations (1 h, 5 X 10(-3) M) exerted protective effects against TEM challenging but not against MH. PMID- 3110616 TI - Nurses move outside traditional roles. PMID- 3110617 TI - Rapid uptake and esterification of arachidonic acid and other fatty acids by microfilariae of Brugia malayi. AB - We have examined the differential incorporation and esterification of exogenous fatty acids by microfilariae of the human filarial parasite Brugia malayi. Microfilariae incubated with 2 nM [3H]arachidonic acid over 1 h rapidly took up this fatty acid. Palmitic, oleic and linoleic acids were also incorporated by parasites. In contrast to these other fatty acids, little incorporated arachidonic acid remained as free fatty acid within microfilariae. Arachidonate was rapidly esterified into phospholipids, with 66% of incorporated arachidonate esterified into phospholipids at 1 min. Esterification of other fatty acids into phospholipids was quantitatively lesser and occurred into phosphatidylcholine and phosphatidylethanolamine. Arachidonate was preferentially esterified into phosphatidylinositol, which constituted only 10% of the total parasite phospholipid pool, and into phosphatidylcholine. By 1 min these two phospholipid classes, respectively, comprised 53% and 43% of [3H]arachidonyl-phospholipids. Neither the microfilarial incorporation of arachidonate nor its esterification into parasite phospholipids could be saturated by noncytotoxic concentrations of up to 600 microM. Microfilariae, which in vivo are exposed to arachidonate in blood, can rapidly, avidly and with high capacity incorporate exogenous arachidonate and esterify it preferentially into specific classes of phospholipids, including phosphatidylinositol. Like many mammalian cells, these phylogenetically distinct metazoan parasites possess efficient means for utilizing host-derived arachidonic acid. PMID- 3110618 TI - Importance of severity of illness in outcome assessment. PMID- 3110619 TI - Transfusion-associated hepatitis and AIDS. What is the risk? AB - Infectious complications have been, and will continue to be, a problem in recipients of blood transfusions. Steps to exclude high-risk donors and to test for antibody to HIV, antibody to hepatitis B core antigen, and alanine aminotransferase almost surely have a beneficial effect on the blood supply. The risk of transfusion-transmitted infectious disease will never be nonexistent, and each transfusion will always have to be considered in terms of benefit versus risk. Patients and physicians need to understand that an absolutely safe blood supply is an unattainable goal, but that current approaches to donor selection and testing are highly effective in minimizing the risk of transfusion transmitted infection. PMID- 3110621 TI - Molecular distinction between muscarinic acetylcholine receptor subtypes. AB - The muscarinic acetylcholine receptor (mAChR) mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels, through the action of guanine nucleotide-binding regulatory proteins. Pharmacologically distinguishable forms of the mAChR occur in different tissues and have provisionally been classified into M1 (I), M2 cardiac (II) and M2 glandular (III) subtypes on the basis of their difference in apparent affinity for antagonists. In an attempt to elucidate the molecular basis of the functional heterogeneity of the mAChR, we have cloned and sequenced DNAs complementary to porcine cerebral and cardiac messenger RNAs encoding mAChRs and have thereby deduced the primary structures of the receptor proteins. We report here that the messenger RNA generated by transcription of the cardiac complementary DNA directs the formation of a functional mAChR in Xenopus oocytes and that this mAChR differs from the mAChR formed by expression of the cerebral cDNA both in acetylcholine (ACh)-induced response and in antagonist binding properties. Our results provide evidence indicating that the mAChR encoded by the cerebral cDNA (designated as mAChR I) and the mAChR encoded by the cardiac cDNA (mAChR II) are of the M1 (I) and the M2 cardiac (II) subtype, respectively. PMID- 3110622 TI - Cross-examination ends in TPA patent case. PMID- 3110620 TI - TPA patent battle continues in court. PMID- 3110623 TI - Arachidonic-acid metabolites as second messengers. PMID- 3110624 TI - G proteins: control of exocytosis. PMID- 3110625 TI - US patents in the balance. PMID- 3110626 TI - Wellcome versus Genentech result. PMID- 3110627 TI - Evidence for a physical association of CD4 and the CD3:alpha:beta T-cell receptor. AB - CD4 is a molecule expressed on the surface of T lymphocytes which recognize foreign protein antigens in the context of class II major histocompatibility complex (MHC) molecules. Recognition of antigen:class II MHC complexes by CD4+ T cells can be inhibited by anti-CD4 (ref. 3). Nevertheless, specific recognition of the antigen:Ia complex is clearly a function of the T-cell receptor, which is composed of CD3 and the variable polypeptides alpha and beta. Thus, it has been proposed that CD4 serves an accessory function in the interaction of CD4+ T cells and Ia-bearing antigen-presenting cells by binding to non-polymorphic portions of class II MHC molecules and stabilizing the cell interaction. Based on our observation that anti-CD4 could inhibit activation of a cloned line of CD4+ T cells by antibodies directed at a particular epitope on the variable region of the T-cell receptor, we have recently proposed that CD4 is actually part of the T cell antigen recognition complex, physically associated with CD3:alpha:beta. But numerous studies showing that CD3 and CD4 are not stably associated on the T-cell surface would appear to contradict this model. Here we show that anti-T-cell receptor antibodies can co-modulate expression of the T-cell receptor and CD4, and that the monovalent Fab fragment of such an anti-T-cell-receptor antibody can, in conjunction with bivalent anti-CD4 antibody, generate an activating signal for the T cell. These findings provide further evidence for a physical association of the T-cell receptor complex and CD4. PMID- 3110628 TI - Hominoid nasal region polymorphism and its phylogenetic significance. AB - The morphology of the nasal bones and their articulations with the adjoining frontal and maxillary bones have recently been reported in Nature and elsewhere to be diagnostic of hominoid taxa, and cladistic analysis based on these features has been used to assign two immature Plio-Pleistocene hominoids (AL 333-105 and Taung) to different lineages (Paranthropus and Homo, respectively). Because earlier studies had established that hominoid crania are highly variable intraspecifically, it seemed desirable to try to replicate the study reporting a consistently different pattern for each hominoid taxon. My results show extensive polymorphism in the nasal region within every taxon of extant pongids, including several rather clear examples, in extant Pan troglodytes, of that recently hypothesized to be a 'paranthropine' pattern. These findings underscore the substantial risks inherent in cladistic analyses using very restricted character sets to assign individual specimens to particular taxa. PMID- 3110630 TI - Economics of health promotion. PMID- 3110629 TI - Allosteric properties of the 5-HT2 receptor system of the rat tail artery. Ritanserin and methysergide are not competitive 5-HT2 receptor antagonists but allosteric modulators. AB - We present an analysis of the interactions of 5-hydroxytryptamine (5-HT) and antagonists (methysergide, ketanserin, ritanserin) with the 5-HT2 receptor system of strips of rat tail artery. The mode of action of ritanserin was also studied on strips of calf coronary arteries. 1. Ketanserin competitively antagonized 5-HT induced effects in rat tail artery with an affinity (pKB = 9.4 nmol/l) consistent with the assumption of an interaction of 5-HT and ketanserin at 5-HT2-receptors. 2. Methysergide reduced to 50-60% the maximum response to 5-HT in rat tail artery. Concentration-effect curves for 5-HT became biphasic in the presence of methysergide with quickly and slowly developing contractions at low and high concentrations of 5-HT, respectively. 100 nmol/l ketanserin completely restored effects of 5-HT depressed by low concentrations of methysergide (less than 10 nmol/l). Higher concentrations of methysergide in the presence of 100 nmol/l ketanserin again depressed the effects of 5-HT. 3. Ritanserin resembles methysergide by causing insurmountable antagonism of 5-HT-induced contractions which can be prevented by ketanserin in both rat tail artery and calf coronary artery. These results are inconsistent with competition between ritanserin and 5 HT for the 5-HT2 receptor. 4. The findings are consistent with the assumption of an interaction of ketanserin and methysergide or ritanserin with an allosteric site near the 5-HT2-receptor. Both methysergide and ritanserin appear to antagonize the effects of 5-HT through an allosteric site which is distinct from the 5-HT2 receptor. PMID- 3110631 TI - Patient care demands by DRG: a pilot study. PMID- 3110632 TI - Cost-effective continuing education. PMID- 3110633 TI - [Revised description of the concept of the rhesus-negative blood donor]. PMID- 3110634 TI - Benchmark of NHS. PMID- 3110635 TI - [Changes in the excitability of motor neurons and synaptic effects on them during formation of the generator of scratching movements in the cat]. AB - It is shown that the state of the segmental apparatus of the lumbal spinal cord of immobilized intercollicularly decerebrated cats during formation of a scratching generator is essentially different from that of a spinal animal. The excitability of "aiming" and "scratching" motoneurons increases, recurrent and reciprocal Ia inhibition of motoneurons becomes stronger and influence of Ib afferents weaker. The flexor reflex afferents exert inhibitory influences on "aiming" motoneurons. After spinalization these influences become excitatory, and the inhibitory influences on "scratching" motoneurons become weaker. The functional role of described changes is discussed. PMID- 3110636 TI - Nonmutagenicity of betel leaf and its antimutagenic action against environmental mutagens. AB - Betel leaf (Piper betel) water and acetone extract are nonmutagenic in S. typhimurium strains with and without S9 mix. Both the extracts suppress the mutagenicity of betel quid mutagens in a dose dependent manner. Moreover both the extracts of betel leaf reduce the mutagenicity of benzo(a)pyrene and dimethylbenzanthracene. Acetone extract is more potent than water extract in inhibiting mutagenicity of environmental mutagens. PMID- 3110637 TI - [An unusual cerebrovascular amyloidosis simulating chronic encephalitis]. PMID- 3110638 TI - Parenteral nutrition via the peritoneum with dextrose and amino acids. AB - We filled the peritoneal cavity of 9 rabbits through a silastic pediatric Tenckhoff-type catheter with a volume 10% of the animal's weight of an isotonic 'absorption mass' made up by a hydroelectrolytic solution to which 535 mg/dl glucose and 2.53 g/l L-amino acids were added. Then we slowly and continuously infused into it a mixture of a 50% glucose solution with a 13.3% L-amino acid solution to provide 10 +/- 0.2 g glucose and 2.18 +/- 0.24 g L-amino acid (0.334 +/- 0.039 g nitrogen) per kilogram weight in 24 h. So we mimicked the scheme and quantities of total parenteral nutrition. Osmolarity and volume of peritoneal fluid were constant throughout the experiment. In the first 4 h, glucose concentration rose to 1,407 +/- 431 mg/dl and amino acids decreased to nearly two thirds of their initial concentrations. Thereafter, both amino acid and glucose concentrations stabilized. Blood sugar rose slightly from basal 145 +/- 16 mg/dl to a maximum of 200 +/- 59 mg/dl. Plasma amino acids showed a moderate but irregular variation with increases in proline, glutamic acid, methionine, lysine and arginine concentrations, a decline of isoleucine and tryptophan concentrations and no changes for the other amino acids given. There were no variations in plasma values of sodium, potassium, chloride, urea, creatinine, osmolarity, total proteins and hematocrit. We achieved a glucose absorption of 8.72 +/- 0.94 g/kg weight (87.07 +/- 10.11% of the administered amount) and a nitrogen absorption of 303 +/- 47 mg/kg/day (91.4 +/- 14% of administered amount).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110639 TI - [Diagnostic and therapeutic problems of osteomeningeal defects and traumatic cerebrospinal fluid defects of the anterior floor of the base of the skull. Apropos of 95 cases]. AB - The authors here report teaching drawn from the latest ninety five cases of osteo dural defects in basilar skull fractures they have surgically treated. They particularly insist on the following points: Difficulties in establishing a clinical diagnosis when the traumatism is in its acute stage: initially 55% of patients do not show any symptom of rhinorrhea, so that the diagnosis is only based on X-ray data. Previous to any surgical treatment the number of serious septic meningitis is rather high in as much as it reaches 10.55% in this series. Risk of infection together with bone damages incite the authors to suggest a surgical treatment of dural defects in their acute stage, namely within the two weeks following the accident. The study of results shows that due to treatment complications, are not insignificant. The authors then tackle the problems of technics and osteo-dural restoration. They, at last, explain, in this series, the interest of preventive antiepileptic treatment by hydantoins during and after the operation. Despite complications due to treatment the results in this series appear to be significant enough to allow the authors to place the indication of the surgical treatment of traumatic osteo-dural defects in basilar skull at the acute stage of their evolution. PMID- 3110641 TI - [A case of Recklinghausen's disease with bilateral tumors of the cerebellopontile angle]. AB - A case of bilateral cerebellopontine angle neuroma in a patient with von Recklinghausen's disease was treated successfully surgically. PMID- 3110640 TI - Role of early edema in the development of regional seizure-related brain damage. AB - Kainic acid-induced seizures produced early (2 hr) generalized edema and later (24 and 48 hr) necrotic edema in temporal cortex and hippocampus as measured by specific gravity changes. Mannitol given during the seizure partially protected against the early edema and prevented the necrotic edema indicating early edema may play a role in later brain damage. However, H2O intoxication, causing much greater generalized edema than the kainic acid-induced seizures, caused no necrotic edema in temporal cortex or hippocampus at 48 hr. Thus it appears that mannitol protection against kainic acid-induced brain damage may be by a mechanism in addition to dehydration. PMID- 3110642 TI - A suspected case of late-onset sodium-valproate-induced hepatic failure. AB - A 15-year-old boy was under anti-epileptic medication (diphenylhydantoine, phenobarbital and Na valproate) for more than five years. He was admitted in cerebral coma and died after 24 hours. The histological findings suggest a valproate induced liver toxicity. This long interval between start of treatment and a possibly related hepatic failure has not been described. PMID- 3110643 TI - Sodium valproate: effects on maternal behaviour in the mouse. AB - The behaviour of lactating mice in their home cages was examined by ethological procedures at 1, 7, 14 and 21 days postpartum. Early in lactation, maternal behaviour was more frequent in the light phase of the 24 hr cycle, whereas non social activity occupied a greater amount of time during the dark phase. As the pups became older, maternal behaviour declined, and at 21 days the dams showed a marked increase of solitary immobility. Behavioural alterations produced by the administration of sodium valproate at 600 mg/l as drinking fluid during pregnancy and lactation (group SVP), and during lactation only, (group PN) were assessed. (Intake of drug amounted to 153 mg/kg during gestation and 186 mg/kg in lactation). Dams of group PN showed behavioural differences from controls in late lactation, pup nursing being prolonged at day 14 postpartum and the frequency of all categories of active behaviour, other than nursing and nestbuilding, was increased at day 21 postpartum in the dark phase of their daily cycle. There was not significant effect on categories of behaviour in dams of the SVP group. Overall, sodium valproate, at this dose, did not reduce maternal care. PMID- 3110644 TI - Baclofen exacerbates epileptic myoclonus in kindled rats. AB - Electrically kindled rats exhibit myoclonic jerks (1-25/min for 30-90 min) when injected with 200 mg/kg i.p. cysteamine. L-Baclofen, 10 mg/kg i.p. injected 45 min prior was not anticonvulsant but rather exacerbated the myoclonus. Furthermore, baclofen itself induced myoclonus in 29% of kindled rats at 10 mg/kg and in 100% of kindled rats at 15 mg/kg. These findings suggest that caution should be exercised before proposing the use of baclofen as an anticonvulsant or indeed using baclofen in patients who are predisposed to seizures. PMID- 3110645 TI - Dialysis dysequilibrium syndrome in neurosurgical patients. AB - Four neurosurgical patients with acute renal failure are presented. Intracranial pressure (ICP), cerebrospinal fluid (CSF) osmolality, and plasma osmolality were measured before, during, and after hemodialysis. There was an increase in ICP during all six hemodialyses performed on these patients. An osmolality gradient was established between the plasma and the CSF during four hemodialyses performed on two patients but not during one hemodialysis on one other patient. Continuous ventricular drainage and ICP monitoring were simple and effective clinical methods to avoid irreversible herniation during hemodialysis in these patients. A review of the literature on, proposed pathogenesis of, and prophylactic possibilities for dialysis dysequilibrium syndrome in neurosurgical patients is presented. PMID- 3110646 TI - Lateralization of a moving auditory image in patients with focal damage of the brain hemispheres. AB - Perception of the moving fused auditory image resulting from dichotic click-train stimulation was studied in 53 patients with focal damages of the temporal lobes. Patients with the right- and left-side damage differed in the click rate for perceived movement and in the movement trajectory length. The data are discussed in connection with right hemisphere specialization for directional hearing. PMID- 3110647 TI - The effects of the age of intracerebroventricular grafts of normal preoptic area tissue upon pituitary and gonadal function in hypogonadal (HPG) mice. AB - Hypogonadal mice are deficient in the hypothalamic gonadotrophic hormone releasing hormone and as a consequence postnatal testicular development does not occur. Grafting preoptic area tissue from normal mice directly into the hypogonadal third ventricle dramatically reverses the hypogonadism; however, the age of the grafted preoptic area tissue is crucial to the survival and function of the graft. Grafting embryonic tissue (E16-18) resulted in 69% of the hypogonadal mice increasing testis weight some sevenfold within 30 days (5.6 to 35 mg). Postnatal day 1 (P1) tissue grafts elicited a similar rise in testis weight in 77% of recipients, whereas P5 tissue was only successful in 22% of cases. In this experimental group, however, testis weight also increased sevenfold compared with hypogonadal untreated mice. Stimulation of testicular growth in the E16-18 and P1 experimental groups was accompanied by an increase in pituitary gonadotrophic hormone content. P10 tissue did not stimulate testis growth nor was pituitary gonadotrophic hormone control elevated and the majority of grafts failed to survive over the 30 day period of the experiment. The present study has shown that the age of grafted tissue is critical in the restoration of physiological function in hypogonadal mice, and that gonadotrophic hormone releasing hormone neurons from E16-18, P1 and P5 preoptic area grafts that survive the 30 day period of the experiment and whose axons reach the median eminence portal vessels are equipotent in stimulating pituitary gonadotrophin synthesis and secretion. PMID- 3110648 TI - Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system. AB - We treated 18 clinically definite relapsing-remitting MS patients with recombinant gamma interferon in a pilot study designed to evaluate toxicity and dosage. Patients received low (1 microgram), intermediate (30 micrograms), or high (1,000 micrograms) doses of interferon by intravenous infusion twice a week for 4 weeks. Serum levels of gamma interferon were proportional to dose and no interferon was detected in CSF. Seven of the 18 patients had exacerbations during treatment, a significant increase compared with the prestudy exacerbation rate (p less than 0.01). Exacerbations occurred in all three dosage groups and were not precipitated by fever or other dose-dependent side effects. There were significant increases in circulating monocytes bearing class II (HLA-DR) surface antigen, in the proliferative responses of peripheral blood leukocytes, and in natural killer cell activity. These results show that systemic administration of gamma interferon has pronounced effects on cellular immunity in MS and on disease activity within the CNS, suggesting that the attacks induced during treatment were immunologically mediated. Gamma interferon is unsuitable for use as a therapeutic agent in MS. Agents that specifically inhibit gamma interferon production or counteract its effects on immune cells should be investigated as candidates for experimental therapy. PMID- 3110649 TI - Cortical generators of somatosensory evoked potentials to median nerve stimulation. AB - In 12 patients with intractable partial seizures, chronically implanted subdural electrodes were used to define the relationship of the epileptogenic focus to cortical functional areas. Cortical somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded from these electrodes. The initial cortical positivity, postrolandic primary cortical potential (PCP), was recorded in all 12 patients with a mean latency of 22.3 +/- 1.6 msec. A potential of opposite polarity, prerolandic PCP, was defined in nine patients with a mean latency of 24.1 +/- 2.7 msec. The latency of the postrolandic PCP was 1.61 +/- 1.59 msec shorter than the prerolandic PCP (p less than 0.01, paired t test). The maximum amplitude postrolandic PCP was 2.1 times larger than the maximum prerolandic PCP (p less than 0.02, paired t test). The phase reversal of the SEPs was compared with the position of the rolandic fissure (RF) defined by electrical stimulation. This study shows that the latency and amplitude characteristics of post- and prerolandic PCPs are significantly different and give support to the concept that they are produced by different generators; and cortical SEPs are helpful in locating the RF. PMID- 3110651 TI - [Current criteria for the selection of amino acid solutions]. PMID- 3110650 TI - [An intravenous penicillin-erythromycin lactobionate combination in the treatment of bacterial endocarditis caused by enterococcus]. PMID- 3110652 TI - [Supportive parenteral nutrition in surgical patients at risk. Prognostic findings in 80 cases]. PMID- 3110653 TI - [Infections caused by central venous catheters in patients under total parenteral nutrition. Usefulness of Seldinger's guidewire]. PMID- 3110654 TI - [Comparative clinical study of tiaprofenic acid and lysine acetylsalicylate in aged osteoarthrosis patients]. AB - Thirty elderly patients (mean age 74) with osteoarthritis effecting various joints were treated with an oral suspension of either tiaprofenic acid (TA) (600 mg per diem b.i.d.) or lysine acetyl salicylate (1800 mg per diem b.i.d.) for 3-6 months in an open randomized experimental study. The parameters of efficacy assessed were pain at rest and under load, stiffness, ability to perform a pre selected daily exercise and joint movements hampered by the disease. Blood flow, liver and kidney function and side effects were examined on a monthly basis. The tiaprofenic acid proved more effective in reducing pain and aiding functional recovery and was also better tolerated, especially at gastrointestinal level. Nine patients under lysine acetyl salicylate and 2 under tiaprofenic acid were forced to suspend treatment due to pyrosis, epigastralgia ed dyspepsia. PMID- 3110655 TI - [Whiplash headache]. PMID- 3110656 TI - [Menstrual disorders of adolescence]. PMID- 3110657 TI - Regulatory concerns: home care. PMID- 3110658 TI - Demography of dialysis and transplantation in Europe, 1984. Report from the European Dialysis and Transplant Association Registry. AB - The demography of renal replacement therapy up until the close of 1984 in Europe is presented, based on return of individual patient questionnaires to the EDTA Registry. These were completed by 84.7% of known centres in 33 countries. Of 187,267 individually registered patients, 102,276 were known to be alive on defined forms of renal replacement therapy on 31 December 1984. The stock of patients alive on treatment by dialysis and transplantation in Europe continued to grow and exceeded 200 per million population in 14 European countries at the end of 1984. During the same year, 21,198 new patients were accepted for treatment in Europe, and crude acceptance rates for new patients exceeded 60 per million population in four countries. Acceptance rates for elderly patients continued to increase and age specific acceptance rates for males aged 65 and over exceeded 100 per million population in 12 countries. A total of 6802 renal transplants were reported during 1984. Regrafting accounted for a higher proportion of transplants in Nordic countries and in the United Kingdom, compared with other nations. During 1984 the total number of transplants reported to the Registry passed 50,000. The distribution of primary renal disease amongst adult patients commencing treatment in 1984 is presented. Amongst elderly patients commencing treatment, a strikingly high proportion have chronic renal failure of uncertain aetiology. Finally, causes of death have been analysed amongst adult patients dying during 1984, showing myocardial ischaemia and infarction to be the leading cause of mortality. PMID- 3110659 TI - Host defence in continuous ambulatory peritoneal dialysis: the effect of the dialysate on phagocyte function. AB - Peritoneal dialysis fluid was examined after dwell periods of from 30 min to 18 h. Macrophages formed more than 70% of all cells recovered, irrespective of dwell time. The viability of these cells was 95% or greater even in 30 min effluent. Peritoneal macrophages and polymorphonuclear leucocytes were incubated in unused peritoneal dialysis fluid. By 30 min the viability of polymorphonuclear leucocytes had fallen to 50% but that of peritoneal macrophages was still 84%. However, phagocytosis of unopsonized zymosan by both cell types was depressed after only 10 min exposure. Peritoneal dialysis effluents obtained after dwell times of 30-180 min were examined for their effect on phagocytosis in vitro. These fluids suppressed peritoneal macrophages function as compared to RPMI 1640. Effluent after an overnight dwell did not affect phagocytosis. The suppressant effect decreased with increasing dwell time. Polymorphonuclear leucocytes were affected to a greater degree than peritoneal macrophages. Tests showed that this decreased phagocytosis was not due to cell death nor was it due to the osmolality or lactate content of the dialysate. Adjusting pH only improved cell function slightly. Phagocyte function appears to be depressed for clinically significant periods of the CAPD cycle. PMID- 3110660 TI - An ultrastructural morphometric study of membranous glomerulonephritis. AB - Sixteen cases of membranous glomerulonephritis and 17 controls were studied using electron microscopy and morphometry of whole glomerular cross-sections. It was found that, in relation to controls, in membranous glomerulonephritis the following parameters are increased: total area, total number of cells, all basement membrane parameters, visceral epithelium compartment area and visceral epithelial cell area, area of parietal epithelium, mesangium and urinary space, number of endothelial and mesangial cells; by contrast, the following are decreased: number of visceral epithelial cells, capillary and endothelial volume fractions. Correlation analysis between morphometric and clinical parameters demonstrated significant correlations between capillary basement membrane thickening and duration of disease, proteinuria and renal function; the changes in visceral epithelial cells correlated with serum albumin, proteinuria and inverse of creatinine; changes in relative area of capillary lumina correlated with blood pressure. It is concluded that the ultrastructural morphometric study of renal biopsies will lead to better understanding of glomerular disease. PMID- 3110661 TI - Acquired cystic disease of the kidney in patients with end-stage chronic renal failure: a study of prevalence and aetiology. AB - Renal ultrasound scanning was performed in 100 patients with end-stage renal failure treated by both haemodialysis and continuous ambulatory peritoneal dialysis (CAPD). Each kidney was assessed for the presence of acquired cystic disease and solid lesions. The appearances were divided into five grades from grade 0 (no cysts detected) to grade 4 (greater than 15 cysts per kidney). Other intra-abdominal organs were also scanned for the presence of cysts. The findings were then correlated with possible aetiological factors, including the type of dialysis used. Sixty-three percent of all the patients had acquired cystic disease of the kidney (ACDK). No solid lesions were found and no cysts were detectable in other organs. The presence and grade of ACDK did not correlate with the age or sex of the patient, the nature of the underlying renal disease, or the duration of chronic renal failure. There was a significant correlation between the grade of ACDK and the duration of both haemodialysis (P less than 0.001) and CAPD (P less than 0.01). The presence of residual renal function did not influence the development of cysts. ACDK had no effect on haemoglobin or other laboratory parameters measured. PMID- 3110662 TI - A prospective randomised comparative study on the influence of cyclosporin and azathioprine on renal allograft survival and function. AB - To study the effectiveness and nephrotoxic side-effects of cyclosporin A (CsA) in renal transplant recipients, a prospective randomised trial was designed to compare CsA with azathioprine (Aza). Each treatment group consisted of 40 patients; in the CsA group, 18 were randomly selected for conversion to Aza after 3 months. The 1-year graft survival for CsA-treated patients was 87% compared with 66% for the Aza group (P = 0.033). Anti-rejection therapy was administrated to 78% of the patients in the Aza group and 47% of those in the CsA group (P less than 0.01). There was no difference in the incidence of primary non-functioning kidneys, cytomegalovirus infections, hypertension, or degree of proteinuria between the two treatment groups. At 3 months the mean creatinine clearance was 42 +/- 2 ml/min (mean +/- SEM) for the CsA group compared with 56 +/- 4 ml/min for the Aza group (P less than 0.01), whereas the mean creatinine clearances at 6 months for both the converted and the non-converted CsA-treated patients did not differ from that found in the Aza-treated group. At 1 year, the mean creatinine clearance for CsA-treated patients who were converted to Aza was higher than that found for Aza-treated patients (62 +/- 7 vs 50 +/- 6 ml/min; P less than 0.05). Furthermore, the increment in creatinine clearance observed after conversion from CsA to Aza at 3 months showed a linear relationship (r = 0.9061) with the CsA trough levels before discontinuation of the drug. This indicates that CsA treatment induces a dose-dependent, nephrotoxic side-effect which is probably reversible. PMID- 3110663 TI - Parathyroid adenoma causing persistent hypercalcaemia after rhabdomyolysis induced acute renal failure. AB - Persistent hypercalcaemia developed in a 26-year-old man after rhabdomyolysis induced acute renal failure. Although several serum parathyroid values were normal following recovery of renal function, primary hyperparathyroidism was suspected after 9 months of prolonged hypercalcaemia. A single parathyroid adenoma was removed and serum calcium as well as serum parathyroid hormone returned to normal values. The persistence of increased serum calcium concentrations after rhabdomyolysis-induced acute renal failure should lead one to consider other causes of hypercalcaemia, and particularly primary hyperparathyroidism. PMID- 3110664 TI - The effect of heating to inactivate human T-cell lymphotropic virus type III (HTLV-III) on calcium and phosphate assays in haemodialysis sera. PMID- 3110665 TI - Demography of dialysis and transplantation in children in Europe, 1984. Report from the European Dialysis and Transplant Association Registry. AB - The demography of treatment of children by renal replacement therapy in Europe is presented based on returns of individual patient questionnaires to the EDTA Registry up until the close of 1984. Patient questionnaires for 1984 were completed by all centres which defined themselves as special paediatric units. A total of 4983 patients have been reported to the Registry up until 31 December 1984 as having commenced renal replacement therapy under the age of 15. Of these, 1570 were known to be alive on a defined form of treatment at the end of 1984 and still under the age of 15. The numbers of these patients kept alive by different forms of treatment in individual countries are presented. The stock of patients aged under 15 at the end of 1984 exceeded 30 per million child population in Belgium, France, Iceland and Luxembourg. The highest age specific acceptance rates for children onto renal replacement therapy during 1984 were noted in those aged between 10 and 14 at first treatment. Age specific acceptance rates for children varied greatly between individual countries, and 18 countries reported no new patients under the age of 5 during 1984. Transplant activity in paediatric patients during 1984 has been analysed and results on regrafting presented. Proportional distribution of primary renal diseases amongst children commencing therapy in 1984 is shown according to age at start of treatment. Haemolytic uraemic syndrome was reported as the cause of end-stage renal failure in 12.0% of children commencing treatment under the age of 5, and 12.3% of children between 5 and 9. Finally, information on cause of death in paediatric patients dying during 1984 is presented, and shows cardiovascular disease was the leading cause of mortality. PMID- 3110666 TI - Abstracts. European Dialysis and Transplant Association-European Renal Association: XXIIIrd annual congress. Budapest, 30 June-3 July 1986. PMID- 3110667 TI - The problem of paid or coerced donors of renal transplants. PMID- 3110668 TI - Dialysis-related amyloidosis. PMID- 3110669 TI - Characterisation and specificity of glomerular basement membrane antigens identified by sera of patients with anti-GBM nephritis. AB - The sera of 21 patients positive for antibodies against GBM in indirect immunofluorescence tests were examined by immunoblotting. We demonstrated antibodies against 50, 48, 43 and 29 kD molecular weight peptides in 20 of 21 sera using collagenase-digested GBM, in 19 of 21 using trypsin-digested GBM, and in 10 of 21 using elastase-digested GBM. Although the spectrum of molecular weights of the antigenic proteins was similar in all three digests, they differed with respect to preservation of antigenicity upon reduction with mercaptoethanol. Many of the sera of patients and controls reacted with proteins unrelated to GBM, e.g. albumin and prealbumin. Furthermore, some control sera reacted with one single peptide of the above-mentioned specific GBM peptides. Our results suggest that the highly purified 29 kD peptide of the collagenase digest or the 50 kD peptide of the trypsin digest provide the best antigens to develop a screening test for antibodies against GBM. However, serum antibodies against these antigens will not be absolutely specific for anti-GBM antibody-mediated nephritis, as shown by the immunoblot experiments. PMID- 3110671 TI - Erythropoiesis in the anaemia of chronic renal failure: the response to CAPD. AB - Fifteen patients with chronic renal failure commencing CAPD treatment were studied by a sensitive ferrokinetic technique. All were severely anaemic with a low red cell volume (RCV). Plasma volume (PV) was raised in twelve. Mean red cell lifespan (MRCL) was reduced in eleven subjects, and marrow iron turnover (MIT) was inappropriately low but this was not related to erythropoietin levels. Six patients were restudied after several months CAPD. PV fell in four and RCV increased in all six. MRCL rose to normal in three. The other three subjects has an increase in MIT. Erythropoietin levels did not change significantly. The major cause of uraemic anaemia is a failure of erythropoiesis to match fully the demands of red cell destruction. PMID- 3110670 TI - Effects of intravenous aspirin on prostaglandin synthesis and kidney function in intensive care patients. AB - The effects of intravenous acetylsalicylic acid (1.0 g bolus) on renal function and prostaglandin synthesis were evaluated in a prospective, controlled study in eight patients in an intensive care unit. Four of these patients had congestive heart failure. Administration of acetylsalicylic acid caused significant antidiuresis (-56%), antinatriuresis (-82%), renin suppression (-26%) and decreased GFR (-41%). All of these changes were completely reversible within 1-2 hours and tended to be more pronounced in the patients with congestive heart failure. Urinary excretion of prostaglandin E2 was depressed profoundly (-93%) and did not return to more than 45% of control 6 h after the administration of acetylsalicylic acid. We conclude that intravenous acetylsalicylic acid affects kidney function in a manner similar to other prostaglandin synthesis inhibitors. Its effects are, however, short-lived. The inhibition of urinary PGE2 excretion outlasts GFR depression, antidiuresis, antinatriuresis and renin suppression by several hours. PMID- 3110672 TI - Propionibacteria isolates and asymptomatic infections of the peritoneal effluent in CAPD patients. AB - During the past two years our laboratory has isolated Propionibacterium-an anaerobic Gram-positive rod-on 40 occasions from the drainage fluid of 25 patients on CAPD and eight on IPD. Most patients had no symptoms and the fluid was sent for culture after treatment of peritonitis, during training period, and occasionally because it was cloudy. No association was found with patients' age, length on dialysis, or previous peritonitis episodes. The only statistically significant association (P = 0.033) was with recent (less than 30 days) catheter insertion. Patients with Propionibacterium as the only organism in their dialysis fluid had normal leucocyte count in the effluent, minimal or no symptoms, and received no treatment. In order to establish the frequency of positive cultures of asymptomatic patients, we cultured 95 dialysate effluents from 33 asymptomatic CAPD patients. Cultures were observed for 4 weeks. We found seven positive fluids (7.4%) in four patients (12%), aerobic sporeformer (2), Staphylococcus epidermidis (2) and Streptococcus viridans (1). The mean time to grow was 18.6 days. In conclusion, effluents from asymptomatic CAPD patients may contain bacteria. The organisms are commensals requiring prolonged incubation to grow. Propionibacterium isolated from peritoneal effluent of patients with minimal or no symptoms does not require treatment. These findings suggest that errors in the technique of CAPD are not rare but when the number of organisms is small and the organism has low virulence, peritonitis does not occur. PMID- 3110674 TI - Acute responses of parathyroid hormone and 1,25 dihydroxyvitamin D3 to unilateral nephrectomy in healthy donors. AB - Plasma immunoreactive parathyroid hormone (iPTH), 1,25(OH)2D3, calcium and phosphate and urinary creatinine, calcium and phosphate were measured before and following unilateral nephrectomy in six kidney donors. Unexpectedly, plasma calcium rose, from 2.27 +/- 0.02 mmol/l (mean +/- SEM) to 2.41 +/- 0.03 mmol/l on day 7 and to 2.37 +/- 0.02 mmol/l on day 30 (P less than 0.02). A parallel rise in iPTH occurred, from 0.61 +/- 0.16 ng/ml initially, to 1.83 +/- 0.54 ng/ml on day 7 (P less than 0.05) and to 1.18 +/- 0.18 on day 30 (P less than 0.01). The ratio of maximal tubular reabsorption of phosphate to GFR (TmP/GFR) fell by day 2 (P less than 0.01), remaining reduced on day 30 (P less than 0.05). The significance of elevated iPTH in renal insufficiency was further assessed by determining the time course of the disappearance of iPTH after parathyroidectomy in three haemodialysis subjects. Fifty per cent baseline iPTH level occurred after an average of 104.7 min, suggesting that the assay did not predominantly recognize C-terminal PTH fragments. By day 2, plasma 1,25(OH)2D3 had fallen from 34.3 +/- 4.5 pg/ml to 22.8 +/- 3.8 pg/ml (P less than 0.001), but by day 4 had regained its pre-nephrectomy value. Our results suggest that hypocalcaemia may not be the sole stimulus to parathyroid hormone secretion. It is speculated that reduction in circulating 1,25(OH)2D3 may be involved. PMID- 3110675 TI - Does lead exposure contribute to deterioration of renal function in patients with renal disease? PMID- 3110673 TI - The role of parathyroid function and parathyroidectomy in the outcome of aluminium-related dialysis encephalopathy. AB - Aluminium (Al) intoxication in patients with chronic renal failure may lead to osteomalacia, microcytic anaemia, and encephalopathy. It has been suggested that the expression of Al toxicity may be related to the function of the parathyroid glands. The purpose of this study was to determine whether the functional state of the parathyroids influenced the evolution of Al-related encephalopathy in Al intoxicated haemodialysed patients. The patients were subdivided into two groups according to outcome: group I patients (n = 6) had died with the clinical feature of severe cerebral dysfunction; group II patients (n = 15) had a favourable outcome with partial or complete recovery. The degree of hyperparathyroidism, as evaluated by plasma biochemistry and bone histology, was comparable in both groups. Three patients of group I and five of group II underwent parathyroidectomy. Before the clinical onset of encephalopathy the duration of Al overload in group I was not different from group II, but after its onset patients of group I were intoxicated significantly longer (8 months +/- 6.6) than those of group II (1.5 months +/- 1.9). This study shows that, in uraemic patients with Al related encephalopathy, parathyroid function and parathyroidectomy do not play an essential role in clinical outcome. The duration of Al intoxication following the first signs of encephalopathy appears to be the major prognostic element. PMID- 3110676 TI - Mercury-induced autoimmune glomerulonephritis: requirement for T-cells. AB - Mercury-induced autoimmunity in Brown-Norway rats has been shown previously to be due to polyclonal activation of B lymphocytes, requiring the presence of T lymphocytes. Autoimmunity in that strain is characterised by the appearance of an autoimmune glomerulonephritis, by the production of a host of autoantibodies, and by an increase in total serum IgE. In the present study, T-cell deprived rats were tested to assess the role of T cells in the appearance of autoimmune abnormalities in vivo. It will be shown that both BN rnu/rnu and BN 'B' rats, who have virtually no T cells, do not develop autoimmunity following HgCl2 injections. In contrast BN 'B' rats reconstituted with normal T cells, and BN rnu/+ rats, exhibit autoimmune manifestations, including autoimmune glomerulonephritis, quite similar to those observed in Brown-Norway rats. These data demonstrate that T cells are essential for mercury-induced autoimmunity to occur in Brown-Norway rats. PMID- 3110677 TI - Plasma met-enkephalin and leu-enkephalin in chronic renal failure. AB - Plasma met-enkephalin and leu-enkephalin has been measured in a group of 28 patients with chronic renal failure, to discover whether these opioids are affected by standard haemodialysis and haemofiltration. Met-enkephalin was markedly higher (P less than 0.001) in uraemic patients than in a group of 13 normal subjects, and was directly related to plasma creatinine (r = 0.60; P less than 0.01) and to plasma urea (r = 0.36; P = 0.06). In contrast, leu-enkephalin was suppressed in uraemic patients (P less than 0.001). Met-enkephalin fell slightly but significantly (P less than 0.02) after both haemodialysis and haemofiltration; however, on average it remained at concentrations four times higher than normal. No changes in plasma leu-enkephalin were observed after haemodialysis and haemofiltration. The cause(s) of the altered plasma concentrations of these opioid substances remains to be clarified. PMID- 3110678 TI - Beta 2-microglobulin kinetics during haemodialysis and haemofiltration. AB - Since the identification of beta 2-microglobulin as a major component of 'dialysis amyloid', concern about its removal by different dialysis methods has been raised. Haemodialysis with regenerated cellulose membranes increases serum beta 2-microglobulin by 10-15%. Serial measurements show a very early increase during cuprophan haemodialysis, the mechanism of which is as yet unknown. After cuprophan haemodialysis, serum values return to the initial pretreatment concentrations by the time of the next haemodialysis. In contrast to regenerated cellulose, dialysis with polycarbonate lowers serum beta 2-microglobulin by 8%, and dialysis with polysulphone by 53%. As opposed to cuprophan, after polysulphone haemodialysis the serum concentrations have not returned to the initial pretreatment levels within 48 h. Comparison of beta 2-microglobulin removal using the same polysulphone membrane for haemodialysis and haemofiltration shows that beta 2-microglobulin is more effectively removed by convection than by diffusion when both treatment modes are matched for blood flow and urea clearance. Therefore, in contrast to haemodialysis with regenerated cellulose membranes, where a transient, intradialytic release of beta 2 microglobulin is induced, significant removal is observed using higher permeable membranes. These findings may have implications for the generation of 'dialysis amyloid'. PMID- 3110679 TI - Cardiovascular and acid-base effects of acetate and bicarbonate haemodialysis. AB - Cardiovascular and acid-base changes were studied in 18 adult haemodialysis patients during a single dialysis against acetate or bicarbonate dialysate. Tachycardia was significantly greater with acetate but, otherwise, blood pressure and peripheral resistance fell and cardiac output increased to a similar degree with the two types of dialysate. Arterial PCO2 increased with bicarbonate and fell slightly with acetate, while hypoxaemia was significantly worse during acetate dialysis. Arterial acetate concentrations increased in 2 of 12 patients during bicarbonate dialysis. No differences in patient symptomatology or hypotensive episodes were noted with acetate or bicarbonate. Any beneficial effects of bicarbonate dialysis are more likely to be related to preservation of arterial PO2 than to the absence of adverse cardiovascular effects of acetate. PMID- 3110680 TI - Effect of haemodialysis on upper gastrointestinal tract pathology in patients with chronic renal failure. AB - Upper gastrointestinal tract pathology observed at autopsy in 94 patients with end-stage renal disease (GFR less than 10 ml/min) was analysed retrospectively. To better evaluate the effect of haemodialysis on this pathology, the chronic renal failure patients were subdivided into three groups: 19 patients who had died before haemodialysis treatment could be undertaken (group I), 21 patients who had died during the first month (group II), and 54 patients who had died after at least one month of haemodialysis treatment (group III). The results revealed that the number of patients with upper gastrointestinal tract pathology was significantly higher in groups I and II (58% and 57% respectively) as compared to group III (31%) and controls (35%). No difference could be demonstrated between group III and controls. The most prevalent lesions observed were gastritis, followed by gastric and peptic ulcers. The incidence of this pathology appeared to decline as the duration of dialysis therapy increased. Mortality caused by upper gastrointestinal tract pathology remained high during the first two years of treatment in group III, despite a smaller incidence of upper tract lesions. This was explained by a relatively higher proportion of haemorrhage. PMID- 3110681 TI - The effect of L-carnitine on lipid metabolism in patients on chronic haemodialysis. AB - Twenty-one patients (median 49 years; range 20-72 years) on chronic haemodialysis (median: 54 months; range 16-154 months) were examined in a clinical controlled trial for the effect of carnitine on hyperlipoproteinaemia. Initial values of serum carnitine were within the normal range. Carnitine was added to the dialysis fluid to a final concentration of 100 mumol/l. The trial was carried out for 6 months, and the serum of fasting patients was analysed at monthly intervals for carnitine, triglycerides, HDL-cholesterol, LDL-cholesterol and apolipoprotein A and B. The loss of carnitine to the dialysis fluid also was examined, as was the retained amount in those receiving carnitine. We could not confirm the findings of others that carnitine produces lowering of serum triglycerides and increases of serum HDL-cholesterol. The study was extended for another year with ten patients; however, no change was observed in the lipid pattern. PMID- 3110682 TI - Chickenpox in adult renal transplant recipients. AB - Five of 610 adults developed chickenpox between 35 days and 9.2 years after renal transplantation, and only one patient survived. All patients received prednisolone and azathioprine during the incubation period. Corticosteroid therapy was continued, but azathioprine was stopped after diagnosis. Four patients were treated with acyclovir, but three were given suboptimal doses. The patient who survived had been taking the lowest dose of azathioprine and was given the recommended dose of acyclovir. All patients who died developed disseminated intravascular coagulation, and at postmortem examination were found to have had cerebral haemorrhage. None of the patients treated with acyclovir had evidence of active varicella-zoster virus infection at post-mortem examination, but two had disseminated bacterial and fungal infections. Chickenpox follows a severe and often fatal course in adults with renal transplants. Prompt acyclovir therapy can be effective, provided an adequate dose is given. Attention should be directed towards prevention by the identification and immunisation of at risk patients prior to transplantation. PMID- 3110683 TI - Survival of sub-optimal cadaver renal grafts with prolonged cold ischaemic times using cyclosporin. AB - Between September 1983 and December 1985, 33 cadaver kidneys with prolonged ischaemic times (mean 47.3 +/- 11.0 h), and frequently in problematic conditions, were received from Europe and transplanted into adults (16 male, 12 female, mean age 34 +/- 11 years) and children (2 male, 3 female, mean age 8.8 +/- 4.0 years), using cyclosporin (CsA) and steroid immunosuppression. Six patients have died (three with functioning grafts) and 12 grafts have been lost. Eighteen grafts remain functioning, with a mean survival of 27 months. The 1 year actuarial patient and graft survivals were 82% and 69% respectively. The mean time to cessation of haemodialysis was 17 +/- 10 days, and to stable graft function was 28 +/- 11 days. At 3 months (27 patients) mean serum creatinine was 191 +/- 88 mumol/l (2.16 +/- 1.0 mg/dl), with a mean CsA dose of 6.7 +/- 2.2 mg/kg per day. There was an association between the immediate post-transplant renographic perfusion index and the serum creatinine at 3 months (r = 0.52, P less than 0.01). At no stage did the serum creatinine correlate with CsA dose or length of ischaemic time. These results demonstrate that despite suboptimal conditions, prolonged cold ischaemic times, and periods of oliguria, cadaver kidney transplants may be managed successfully with CsA and low-dose steroids. PMID- 3110684 TI - Cataractogenic effect of cyclosporin A: a new adverse effect observed in the rat. AB - In a study designed to test the long-term nephrotoxic effects of cyclosporin A (CyA), 11 of 13 rats given CyA, 25 mg/kg per day for 8 months, developed cataract. None of the 15 rats given CyA 12.5 mg/kg per day, nor of the controls given vehicle only (n = 10), developed this lesion. In a subsequent study, 15 rats were given CyA 25 mg/kg per day, 15 were given 12.5 mg/kg per day, and 10 controls were given the vehicle only. After 16 weeks, three rats of the group on CyA 25 mg/kg per day had developed cataract. The SPF Sprague-Dawley rats were maintained on a controlled breeding diet (Ewos R3). Perforating eye lesions or infections were not observed, but one rat without opacity of the lens had antibodies against sialodacryoadenitis virus. Thus, in the rat, high-dose CyA has significant cataractogenic effects when administered for 15%-25% of the rat life span. PMID- 3110685 TI - Varying methods of sterilisation, and their effects on the structure and permeability of dialysis membranes. AB - This study elucidates changes in membrane structure and permeability due to the methods of sterilisation and the conditions under which they are carried out. Tubular dialysis membranes of regenerated cellulose having various values for porosity were sterilised by ethylene oxide gas, autoclave or gamma irradiation under varying conditions. Non-sterilised membranes were included as controls. The solute permeability of the membranes was determined using 14C-urea. The membranes tested showed no difference in clearance of urea or creatinine. Gamma-ray sterilisation under dry conditions greatly reduced the vitamin B12 clearance and hydraulic permeability of membranes with a water content of below 60%. Hydraulic permeability increased with gamma irradiation for membranes sterilised under wet conditions. A reduction in vitamin B12 clearance for membranes with a water content of above 60% resulted after autoclave sterilisation. Pore model calculation reveals that membrane shrinkage resulted from sterilisation both by gamma-rays under dry conditions, and by autoclave. Thus, the structure of dialysis membranes varies with the method of sterilisation and the conditions under which the sterilisation is carried out. PMID- 3110686 TI - Unmasking of subclavian vein obstruction following creation of arteriovenous fistulae for haemodialysis. A problem following subclavian line dialysis? AB - We report three cases of subclavian vein obstruction following haemodialysis by a subclavian line. The obstruction only became apparent clinically following the formation of an arteriovenous fistula on the same side as the initial catheterisation. In each case, gross swelling of the arm followed creation of the fistula. One case responded to treatment with anticoagulants, but the other two required ligation of the arteriovenous fistula with rapid resolution of the swelling. PMID- 3110687 TI - Post-surgical deterioration of renal function in primary hyperoxaluria. AB - Primary hyperoxaluria leading to calcium oxalate urinary stones and renal deposits occurs rarely in adults. We report three cases in whom end-stage renal failure was precipitated by urological surgery. In contrast, in one case renal stones were destroyed by extracorporeal shock-wave lithotripsy and renal function was not significantly altered. This emphasises the need for early diagnosis. This may not be easy in adult patients: urolithiasis may not be severe, radiological nephrocalcinosis may be lacking, and renal failure may develop late in life. PMID- 3110688 TI - Genetic factors in the outcome of idiopathic membranous nephropathy. PMID- 3110689 TI - Pharmacological evaluation of urate renal handling in humans: pyrazinamide test vs combined pyrazinamide and probenecid administration. AB - Uricosuric and antiuricosuric drugs have been utilised widely for the study of tubular urate transport in humans. A normal suppression of urate excretion after pyrazinamide is usually taken as evidence of normal presecretory reabsorption. However, in patients with reduced presecretory reabsorption, during pyrazinamide inhibition of urate secretion unreabsorbed urate might still undergo reabsorption along postsecretory sites, allowing for a normal pyrazinamide suppression of urate excretion. To test this possibility, we have performed the pyrazinamide test both alone and after pretreatment with probenecid, which should block postsecretory urate reabsorption. The test was performed in 8 controls, in 9 patients with 'low-excretory' hyperuricaemia, and in 7 patients with tubular urate wasting. Pyrazinamide-non-suppressible urate excretion after pretreatment with probenecid did not differ from the excretion obtained after pyrazinamide alone in hyperuricaemic patients (mean difference 1.33 +/- 2.3% of filtered urate; P = NS); it was slightly higher in controls (3.4 +/- 3.4; P less than 0.05), but was much higher in patients with tubular urate wasting (19.6 +/- 12.7; P less than 0.005). The pyrazinamide test, performed alone, was normal in three patients with tubular urate wasting, but it was abnormal in all patients after pretreatment with probenecid. These results are consistent with the possibility that, during maximal pyrazinamide effect, some uric acid escaping reabsorption at presecretory sites may undergo reabsorption along postsecretory sites, leading to a quantitative overestimation of presecretory reabsorption. This phenomenon appears to have clinical relevance, especially in patients with abnormal urate reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110690 TI - Appearance of enzymes in plasma or urine following renal injury. AB - The present study evaluates the relevance of plasma enzyme activity in the quantitative assessment of renal injury. In a canine model, enzyme release from kidneys to plasma and urine was studied following an artificial parenchymal enzyme infusion in healthy and ischaemic kidneys. The cumulative enzyme activity in plasma and urine was calculated. Within 1 h of the start of the infusion, 80% of the infused enzyme was recovered in plasma, whereas urinary accumulation was negligible. A similar enzyme distribution between these compartments was obtained if the kidneys were ischaemically damaged before the start of the infusion. Thus enzymes released into the renal cortical interstitium are very rapidly transported to the vascular system and are quantitatively recovered in plasma. Experimental renal infarction revealed that cell death due to ischaemia also resulted in enzyme accumulation in plasma. PMID- 3110691 TI - Effect of methylprednisolone and cyclophosphamide in mercury-induced autoimmune glomerulonephritis. AB - The effects of methylprednisolone and of cyclophosphamide were tested in mercury induced autoimmune disease in Brown-Norway rats. Survival, proteinuria, presence of antiglomerular basement membrane bound antibodies and of immune complex type deposits, amounts of circulating immune complexes, and total serum IgE were studied. Serum IgE represents the most sensitive marker in this drug-induced autoimmune disease. Methylprednisolone alone (1.5 mg/kg per day) affected the course of the disease only slightly. Cyclophosphamide (20 mg/kg every other day) given from day 0 completely prevented all the autoimmune manifestations, but the rats were profoundly immunosuppressed. The same protective effect was obtained with lower cyclophosphamide dosage (15 mg/kg on day 0 and then 2 mg/kg per day). More interestingly, cyclophosphamide given from day 10 or 15 (20 mg/kg twice a week or every other day), at a time when the disease was already expressed, resulted in partial or complete recovery, provided that the rats had not exhibited heavy proteinuria before initiation of treatment. Cyclophosphamide is therefore a powerful agent, able to prevent and even to reduce the consequences of polyclonal activation in this model. PMID- 3110692 TI - Determinants of plasma beta 2 microglobulin concentration: possible relation to membrane biocompatibility. AB - Beta 2 microglobulin (beta 2m) concentrations were measured by radioimmunoassay in the serum of haemodialysed patients. beta 2m was higher in males (n = 48) than in females (n = 26), i.e. 40.3 +/- 10.1 mg/l (SD) vs 31.2 +/- 8.0, P less than 0.01). beta 2m was not significantly higher in patients with bone cysts (37.7 +/- 11.4 mg/l vs 37.0 +/- 10.0), but median duration of dialysis was significantly (P less than 0.01) longer in patients with bone cysts (90 vs 57 months). beta 2m was lower in patients maintained on dialysis for less than 1 year and whose residual urine volume was greater than 0.1 litre per day. During one single session of dialysis, using cuprophane membranes, beta 2m increased acutely at 15 min and had risen by 32.4% at the end of the dialysis session, more than could be explained by haemoconcentration. In contrast, beta 2m acutely decreased by 38.7% during a single session using polysulphone membranes and the steady state predialysis values were lower by 37.1% after two weeks intermittent haemodialysis with polysulphone membranes. After re-exposure to cuprophane serum beta 2m increased to the original value. It is concluded that beta 2m concentrations on dialysis are a function of residual urinary volume, sex, and type of membrane used. Data are consistent with effective removal of beta 2m by membranes with high cut-off. PMID- 3110693 TI - Silicone-induced hypercalcaemia in haemodialysis patients. AB - Silicone spallation from the roller-pump insert in dialysis blood lines leads to the accumulation of silicone in haemodialysis patients, which in turn leads to a foreign-body reaction with granuloma formation. We have studied two patients in whom documented silicone accumulation has been associated with both granuloma formation and significant, persistent hypercalcaemia. In both patients plasma levels of immunoreactive parathyroid hormone and 1,25-dihydroxyvitamin D were low or undetectable. In one patient, hypercalcaemia responded only partially to corticosteroids, but completely to naproxen. Both patients were changed to silicone-free blood lines and their hypercalcaemia subsequently resolved. The results indicate that in some haemodialysis patients, silicone accumulation and granuloma formation may lead to hypercalcaemia that is independent of 1,25 dihydroxyvitamin D, and that may instead reflect altered prostaglandin metabolism. PMID- 3110694 TI - Functional deterioration of the peritoneum: does it occur in the absence of peritonitis? AB - Peritoneal function in relation to the occurrence of peritonitis and the osmolarity of the dialysate was studied in 72 CAPD patients with a mean duration of treatment of 16.5 +/- 9.0 months (group 1). Data from 24 of these patients, who were on CAPD for longer than 2 years (average 28.6 +/- 4.9), were subjected to further detailed analysis (group 2). Each group consisted of two subgroups, one of patients who had experienced peritonitis and one of patients who had had no episodes of peritonitis. Results from group 1 revealed that the use of hyperosmolar bags increased in parallel with the duration of CAPD treatment even in the non-peritonitis subgroup, and that peritonitis enhanced the tendency to use hyperosmolar dialysate solutions. This phenomenon was also observed in the peritonitis subgroup of group 2, but was not apparent in the non-peritonitis subgroup of group 2 when examined as a whole: however, individual analysis revealed that some of them had a similar tendency to use hyperosmolar dialysate, as was seen in the peritonitis subgroup. These results confirm that the peritonitis impairs the ultrafiltration capability of the peritoneum. The results also suggest that the long-term use of hyperosmolar dialysate may be associated with decreased ultrafiltration, hence emphasis should be placed upon the use of hyperosmolar dialysate solutions for long-term CAPD. PMID- 3110695 TI - Factors determining the prevalence of hypertension after renal transplantation. AB - The prevalence of hypertension was studied in renal transplant recipients followed for at least 1 year. Twenty-eight patients with a transplant renal artery stenosis, all with hypertension, were excluded from further study. Hypertension was present at 1 year after transplantation in 48.3% of 329 cadaveric renal graft recipients, treated with azathioprine. These hypertensive patients had experienced more rejection episodes. The prevalence of hypertension was higher in patients with (n = 237) than in those without (n = 92) host kidneys in situ (57.8% and 23.9% respectively, P less than 0.001). In patients with host kidney, the prevalence of hypertension was higher in patients with glomerulonephritis (n = 108) than in those in whom interstitial nephritis (n = 63) was the original renal disease (71.3% and 42.8 respectively, P less than 0.001). In 41 patients initially treated with cyclosporin and in 42 recipients of a kidney from a living donor, the prevalence of hypertension was not clearly lower than in the azathioprine-treated patients. In 30 patients without host kidneys who did not experience acute rejections, only three had hypertension. In all three patients a specific cause for the hypertension was found. In hypertensive patients, blood pressure decreased gradually in the years following transplantation. In conclusion, besides transplant renal artery stenosis, the main determinants of the prevalence of hypertension after renal transplantation are host kidneys original renal disease, and rejection. PMID- 3110696 TI - Measurement of serum C-reactive protein concentration after renal transplantation. AB - A prospective study of serial serum C-reactive protein (CRP) concentrations was made on 21 patients who had received renal allografts. CRP was raised during 27 of 32 rejection episodes and in all of five episodes of rejection associated with infection. CRP values were persistently elevated in three irreversible rejection episodes. Significantly raised CRP concentrations were documented in 14 of 20 episodes of infection. In some cases CRP was a predictive indicator of rejection or infection. In all cases of infection or rejection associated with a rise in CRP, CRP values fell following successful treatment with appropriate agents. Serial CRP measurement used in conjunction with other clinical and biochemical parameters appears to be valuable clinically following renal transplantation. PMID- 3110697 TI - Synergistic effect of photochemical donor pretreatment and cyclosporin therapy of the recipient on rat renal allograft survival. AB - Dose-response studies of cyclosporin (CsA) established that doses of 2 mg/kg body weight on 4 consecutive days (0-3) or higher gave complete suppression of rejection and permanent survival of all rat kidney allografts, while a dose of 2 mg/kg body weight on day 0 was much less effective in preventing deleterious rejection (30% permanent survival). Photochemical pretreatment of the kidney donor with 8-methoxypsoralen (8-MOP) and direct long-wave ultraviolet irradiation (UVA) of the kidney (PUVA) therapy) significantly prolonged the subsequent graft survival in allogeneic recipients. Forty per cent of the animals survived more than 100 days. However, when PUVA-treated kidney allografts were transplanted into temporary CsA immunosuppressed recipients (2 mg/kg on day 0) the graft survival rate was further improved. Seventy per cent of the PUVA + CsA-treated recipients survived permanently. Therefore, a synergistic effect of PUVA pretreatment and low-dose CsA therapy on rat renal allograft survival was demonstrated. The results suggested a possible clinical application of this treatment regimen in order to avoid high nephrotoxic CsA doses. PMID- 3110698 TI - Pancreatitis causes brownish-black peritoneal dialysate due to the presence of methaemalbumin. AB - Two patients treated with continuous ambulatory peritoneal dialysis had striking brownish-black coloured peritoneal dialysate concomitant with underlying pancreatitis. Examination of the second patient's dialysate by recording spectrophotometry showed the discoloration to be due to methaemalbumin. Haemorrhagic pancreatitis, by releasing proteolytic enzymes and perhaps by using the lesser sac as an anatomical cul-de-sac for chemical reaction, provides a suitable milieu for the production of methaemalbumin from red blood cells in dialysate. PMID- 3110699 TI - Renal artery stenosis, erythrocytosis and renal artery occlusion. PMID- 3110700 TI - Desferrioxamine infusion test. PMID- 3110701 TI - Scottish Renal Association meeting. 31 October-1 November 1986. PMID- 3110702 TI - Presence of glucocorticoid receptor immunoreactivity in corticotrophin releasing factor and in growth hormone releasing factor immunoreactive neurons of the rat di- and telencephalon. AB - By means of the indirect immunoperoxidase technique using two-color immunocytochemistry a moderate to strong nuclear glucocorticoid receptor (GR) immunoreactivity was demonstrated in the vast majority of the corticotrophin releasing factor (CRF)-immunoreactive nerve cells of the parvocellular parts of the paraventricular hypothalamic nucleus, of the septohypothalamic nucleus, of the bed nucleus striae terminalis and of the central and medial amygdaloid nuclei. All the growth hormone-releasing factor (GRF)-immunoreactive nerve cells of the lateral magnocellular part of the arcuate nucleus in its entire rostrocaudal extent showed a moderate GR immunoreactivity. These results and others indicate that glucocorticoids may directly affect all the CRF and GRF cell populations projecting into the median eminence as well as CRF and GRF neurons controlling behavioral and autonomic functions. PMID- 3110703 TI - Schistosoma hepatic cirrhosis and bleeding esophageal varices. PMID- 3110704 TI - Manganese neurotoxicity: effects of varying oxygen tension and EDTA on dopamine auto-oxidation. AB - Manganese (Mn) is an essential trace element which, in excess, induces a chronic parkinsonian disease in animals and humans. Previous work indicated that Mn was more potent than other transition metal ions at stimulating dopamine (DA) auto oxidation. We incubated Mn and DA at 37 degrees C and observed optical density changes at 480 nm, which is proportional to aminochrome formation. pO2 was held at O(N2), 160(O2), or 720 mm Hg(95%O2). Air without Mn produced approximately the same oxidation rate as Mn under N2; air plus Mn (33 uM) yielded a rate 5-fold greater than either air or Mn alone. Under elevated pO2, Mn (10 uM) produced approximately twice the rate seen with air. Addition of the chelating agent (EDTA, 1 mM) produced an 80% decrease in Mn-stimulated DA auto-oxidation. Results are consistent with a role for activated oxygen metabolites in DA depletion seen in chronic Mn intoxication. PMID- 3110705 TI - Specific carbohydrate expression by small-diameter subclasses of rabbit trigeminal, glossopharyngeal, and vagal afferent fibers studied with the lectin Ulex europaeus agglutinin I. AB - Lectin Ulex europaeus agglutinin I (UEAI), which binds to some alpha-L-fucose containing carbohydrates, specifically labeled a subset of trigeminal, glossopharyngeal, and vagal ganglion cells and their axons in the rabbit. The UEAI-positive trigeminal afferent fibers traveled through the spinal tract of the trigeminal nerve and terminated predominantly at the superficial laminae of the caudal region of the nucleus of the spinal trigeminal tract. The trajectory and termination regions of the UEAI-positive trigeminal afferent fibers as well as their small diameters suggest that they are C-fibers which mediate nociceptive and/or thermoceptive inputs. The UEAI-positive vagal and glossopharyngeal fibers were also of small diameter and traveled through the solitary tract. They projected to the nucleus of the solitary tract and the area postrema. No central neurons in the brainstem were labeled with UEAI. These results indicate that subsets of trigeminal, glossopharyngeal, and vagal primary sensory neurons express specific carbohydrates on their cell surfaces. PMID- 3110706 TI - Specialized nutrition regimens for seriously ill patients. PMID- 3110707 TI - Lipofuscin production during total parenteral nutrition. PMID- 3110708 TI - Essentiality of copper in humans. PMID- 3110709 TI - Patient care systems vs. financial systems: the cost justification battle. PMID- 3110710 TI - Is endometriosis an autoimmune disease? AB - Among 59 laparoscopically staged endometriosis patients, 28.8% tested positive for antinuclear antibody. Of 44 patients, 45.5% were lupus anticoagulant positive (greater than 1.3) and 20.5% were within a borderline range (1.2-1.3). Antinuclear antibody positivity was inversely related to stage of disease (P = .009); lupus anticoagulant positivity exhibited a similar trend, but did not reach statistical significance. Of 31 endometriosis patients, 64.5% exhibited immunoglobulin G (IgG) autoantibodies and 45.2% demonstrated IgM autoantibodies to at least one of 16 antigens investigated. Among IgG autoantibodies, those to phospholipids were most frequently detected, followed in order of frequency by antibodies to histones and nucleotides. The incidence of IgM autoantibodies was inverted, with antinucleotides appearing most frequently and antiphospholipids least frequently. A strong correlation was noted between the presence of lupus anticoagulant and antinuclear antibody with both IgG and IgM autoantibodies. These observations suggest that endometriosis is associated with abnormal polyclonal B cell activation, a classic characteristic of autoimmune disease. This contention is further supported in that immunoglobulin levels (particularly IgG) are elevated in patients with endometriosis, and more so in lupus anticoagulant-positive than lupus anticoagulant-negative endometriosis patients (P = .021). PMID- 3110711 TI - Penetration of bacteria and spermatozoa into bovine cervical mucus. AB - It has been reported that bacteria may attach to motile spermatozoa, be carried through the cervix and uterus to the fallopian tubes, and cause acute salpingitis. In an attempt to mimic these conditions in vitro, we incubated Escherichia coli, Streptococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus with motile spermatozoa which then were allowed to migrate through a capillary filled with bovine cervical mucus. After satisfactory sperm migration through the mucus, the capillaries were broken and cultured at different distances from the original insemination site. Mucus fractions in proximity to bacterial inocula grew varying amounts of the pathogens. More distal fractions of mucus columns were generally culture-negative even though they contained motile sperm which had been exposed to bacteria. Migration of spermatozoa exposed to bacteria through bovine cervical mucus did not result in enhanced bacterial penetration. PMID- 3110712 TI - Changes in arterial blood gases following cardiac asystole during fetal life. AB - A case of suspected fetal cardiac asystole with normal umbilical cord blood gas values is reported. Possible explanations of this apparent discrepancy were examined by measuring sequential changes in fetal arterial acid-base and blood gas values after induced cardiac asystole in chronically instrumented fetal lambs at 132-141 days' gestation. Arterial pH values did not decrease from baseline for at least ten minutes. Elevation of pCO2 values were observed at 30 minutes. Arterial pO2 and HCO3 values remained unchanged for at least 30 minutes. Therefore, we conclude that sudden fetal cardiac asystole occurring within ten minutes of delivery may be one reason why umbilical cord acid-base and blood gas values do not correlate with Apgar scores. PMID- 3110713 TI - Ovarian remnant syndrome. AB - Ten patients with "definite" and three patients with "probable" ovarian remnant syndrome are reviewed to emphasize the difficulties in diagnosis and treatment of this clinical problem. Physical examination, clinical history, and follicle stimulating hormone (FSH) levels were sufficient for diagnosis in most cases. Intravenous pyelography documented ureteral obstruction in two cases. Exogenous estrogen and progestin hormones did not control symptoms. Surgical removal ultimately achieved symptom relief for all women in whom pain was well localized to the remnant, although two patients required two attempts at excision before they were cured. Three patients with more diffuse pain and "probable" ovarian remnants were managed medically. Ovarian remnant syndrome is probably more prevalent than is generally appreciated. PMID- 3110714 TI - The short-term effect of pelvic irradiation for gynecologic malignancies on bladder function. AB - Urinary symptoms and urodynamic studies were evaluated prospectively in 33 women undergoing radiation therapy for cervical cancer. Patients were evaluated during treatment, after one to two months, and after five to six months. Significant reductions in peak urinary flow, volume at first desire to void, cystometric capacity, and bladder compliance were evident during and immediately after therapy. Bladder symptoms and urodynamic alteration did not correlate with age, race, or stage of disease. Bladder compliance was significantly reduced in those patients receiving more than 3000 rads to the entire bladder from external beam irradiation. PMID- 3110715 TI - The effect of neodymium:YAG laser shocks on the blood-aqueous barrier. AB - An animal model demonstrates that the acute inflammation seen after neodymium: YAG (Nd:YAG) capsulotomy is related to the presence of disrupted tissue suspended in the aqueous, rather than to the mechanical insults by the repeated shock waves. Seven rabbits were treated in the lens cortex of one eye with 20 bursts of 4 pulses, 24 mJ each, and followed fluorophotometrically using albumin labelled with fluorescein. This allowed transmission of shock waves to the anterior segment without releasing debris in five eyes that showed no inflammation. Two eyes with inadvertent capsular rupture showed marked blood-aqueous barrier breakdown. This suggests the use of a capsulotomy technique that relies on discission rather than pulverization of the membrane and avoids the thicker portions of the membrane when possible. PMID- 3110716 TI - Corneal manifestations of scleromyxedema. AB - Bilateral superficial corneal deposits and scleromyxedema, an uncommon dermatosis caused by the accumulation of acid mucopolysaccharide in the skin often associated with a benign monoclonal gammopathy developed in a 71-year-old man. A biopsy specimen of the cornea showed that the deposits stained strongly positive for IgG and lambda chains. Ultrastructurally, the deposits consisted of amorphous granular material. Scleromyxedema should be considered in the differential diagnosis of noninflammatory superficial keratopathies associated with benign gammopathies. PMID- 3110718 TI - Quality assurance in home health agencies: the role of the clinical pharmacist. AB - Drug therapy for home care patients, most of whom are elderly, is becoming increasingly complex. In addition, these patients are usually left to their own resources to manage drug therapy. Clinical pharmacy services are therefore a vital component to assuring and maintaining positive therapeutic outcomes in home care. The Visiting Nurse Association (VNA) of Baltimore includes clinical pharmacy in its array of existing home health care services. The VNA system is described and two case studies are presented that illustrate how clinical pharmacy services can directly affect quality of care. PMID- 3110717 TI - Severity of illness, quality of care, and physician practice as determinants of hospital resource consumption. AB - Health care providers continue the debate over why it costs more to care for patients than the DRG reimbursement rate allows. This study examines severity of illness (measured by the AS-SCORE rating), quality of care (measured by the Adverse Patient Occurrences Inventory), and physician practice patterns as sources of variability in hospital resource use by patients in two DRGs. Both instruments independently account for some of the intra-DRG variability in length of stay and total charges. The study indicates that there is a positive relationship between severity of illness and decreased quality of care and that physician practice does not affect variation in resource use when cardiovascular complications, severity of illness, and quality of care are controlled. PMID- 3110719 TI - Quality assurance in a PaCS and case-mix environment. Patient Care and Services. AB - Medicare/Medicaid's new long term care certification survey and case-mix payment systems have important managerial implications for quality assurance programs. These implications are explained in this article and recommendations are made to help skilled and intermediate care nursing facilities function effectively in the new environment. PMID- 3110720 TI - Relating quality and cost in a home health care agency. PMID- 3110721 TI - Plasma TSH valuation using immunoradiometric method. PMID- 3110722 TI - Psychiatry in the spinal injuries unit. PMID- 3110723 TI - Effect of the energy source on changes in energy expenditure, respiratory quotient, and nitrogen balance during total parenteral nutrition in children. AB - The effects of three isocaloric intravenous nutritional regimens were studied in seven infants and children, ages 2 months to 9 yr, with congenital gastrointestinal anomalies (four patients) or with prior history of malignant disease admitted in remission for bone marrow transplantation (three patients). Energy metabolism, as measured by the basal metabolic rate (BMR), and substrate utilization, as measured by the respiratory quotient (RQ), were studied to determine the effect of different levels of carbohydrate and fat on nitrogen retention in each patient. Solution A provided 8% of energy as amino acids, 87% as carbohydrate, and 5% as fat. Solution B provided 8% of energy as amino acids, 60% as carbohydrate, and 32% as fat. Solution C provided 8% of energy as amino acids, 34% as carbohydrate, and 58% as fat. Administration of solution A (high carbohydrate, low fat) was associated with moderately increased mean (+/- SD) BMR and RQ and with low nitrogen retention (19.1 +/- 12.7%, 1.06 +/- 0.14, and 98 +/- 28 mg N/kg/day). Both the BMR and the RQ decreased when less carbohydrate and more lipid was given: BMR 4.3 +/- 11.6% (p less than 0.005), RQ 0.92 +/- 0.09 (p less than 0.001) for solution B; BMR 3.94 +/- 10.6% (p less than 0.005), RQ 0.86 +/- 0.09 (p less than 0.001) for solution C. Among the solutions tested, optimal nitrogen retention [163 +/- 60 mg N/kg/day (p less than 0.01)] was noted with solution B. Our data support the conclusion that a physiologic balance of fat and carbohydrate results in optimal nitrogen retention. PMID- 3110724 TI - Diminished polymorphonuclear leukocyte adherence and chemotaxis following protein calorie malnutrition in newborn rats. AB - Recent advances in neonatal care have permitted the survival of very low birth weight infants who are difficult to nourish, and ultimately develop clinical and biochemical signs of malnutrition. These infants may be at greater risk for nosocomial infection than normally nourished hosts. We have compared neutrophil adherence and chemotactic responses in a newborn rat model of protein-calorie malnutrition. Wistar rats at 14 days gestation received either a normal (24% protein) or isocaloric (2.5% protein) diet. On day 5, rat pups were divided into three groups: pups allowed to nurse on their own dam (normal); normally nourished pups foster nursed onto a malnourished mother (depleted); or malnourished pups foster nursed to a normal dam (repleted). Granulocytes from depleted pups demonstrated significantly diminished adherence and chemotaxis when compared to normal or repleted pups. Thus, abnormalities of neutrophil function in malnourished newborn rats may contribute to increased susceptibility to bacterial infection. PMID- 3110726 TI - Variables affecting apolipoprotein B measurements in 3- to 5-day-old babies: a study of 4491 neonates. AB - To investigate the feasibility of establishing a neonatal screening program for familial type II hypercholesterolemia, we assayed apolipoprotein B (Apo B), using a radial immunodiffusion assay, in dried blood spot samples from 4491 consecutively born, 3- to 5-day-old neonates. We explored factors influencing levels at the time of sampling and factors associated with the handling of the dried blood spot samples before assay which could affect the assayed value. Assayed Apo B levels were distributed continuously and decreased with increasing delay and temperature of storage of the samples before assay. Female neonates had significantly higher mean Apo B levels than males (p less than 0.0001), with their respective means +/- SD being 0.246 +/- 0.085 g/liter (n = 2086) and 0.225 +/- 0.079 g/liter of whole blood (n = 2390). In both sexes mean Apo B levels were significantly lower in low birth weight (less than or equal to 2.5 kg) and in low gestational age (less than or equal to 36 wk) neonates. For neonates with birth weight greater than 2.5 kg and gestational age more than 36 wk, Apo B levels increased with increasing birth weight and gestational age. Sex, birth weight, and gestational age could account for 5.7% of the variability of Apo B. After adjustments for these variables, the neonate's age at sampling did not influence Apo B levels significantly. Apo B levels were not affected by different dietary regimens, whether breast-fed, formula-fed, or breast-fed with formula complement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110725 TI - Coupling of ventilation and CO2 production during exercise in children. AB - The purpose of this study was to determine how ventilation (VE) and CO2 production (VCO2) in response to exercise change during the growth process in children and teenagers. Dynamic gas exchange responses were measured in two types of studies: 128 healthy children ranging in age from 6 to 18 yr performed progressive exercise tests ("ramp" type protocol) for measurement of the slope of the relationship between VE and VCO2--delta VE/delta VCO2; and the response characteristics of VE and VCO2 in the transition between rest and exercise were measured in 11 teenagers and 11 younger children. Gas exchange was measured breath by breath. We found a small but significant decrease in delta VE/delta VCO2 with increasing body weight (r = -0.46, p less than 0.05), height, or age (mean slope of 27 in the youngest in 21 in the oldest subjects). The response characteristics of VE and VCO2 (measured as the time constant of the best-fit exponential response) were longer than for VO2 in both younger children and teenagers; but the time constants for VE and VCO2 were each approximately 30% faster in younger children compared to teenagers. In addition, end-tidal PCO2 during exercise was significantly lower in the younger subjects (mean value of 39.6 torr) compared to the teenagers (mean value of 43.5 torr). The results suggest that the process of respiratory control in exercise matures to a small degree during childhood in that PCO2 may be regulated at lower levels in younger children and there may be growth-related differences in the relative amounts of CO2 that can be stored in tissues. PMID- 3110727 TI - Neisseria meningitidis strains with decreased susceptibility to penicillin. AB - Neisseria meningitidis strains relatively resistant to penicillin were recovered from blood or cerebrospinal fluid cultures of four children treated in Barcelona, Spain, and surrounding areas. The four strains had distinct serogrouping and serotyping patterns. The minimal inhibitory concentrations of penicillin were 0.25 microgram/ml for three strains and 0.5 microgram/ml for the fourth strain. These are the first relatively penicillin-resistant meningococcal strains identified in Spain. PMID- 3110728 TI - Streptococcal antigen in the pharynx after initiation of antibiotic therapy. PMID- 3110729 TI - Dose-response relationship of doxapram in the therapy for refractory idiopathic apnea of prematurity. AB - Eighteen infants with idiopathic apnea of prematurity refractory to therapeutic levels of aminophylline were treated with incremental doses of doxapram beginning at 0.5 mg/kg/h. Continuous recording of heart rate, thoracic impedance, and transcutaneous PO2 demonstrated that 47% of the infants satisfied objective response criteria at the lowest dose, 53% responded at 1.0 mg/kg/h, 65% at 1.5 mg/kg/h, 82% at 2.0 mg/kg/h, and 89% at the highest allowed dose of 2.5 mg/kg/h. The mean serum doxapram concentration at the response dose was 2.9 +/- 1.3 micrograms/mL, and all infants who responded had levels greater than 1.5 micrograms/mL. BP was significantly elevated at doses higher than 1.5 mg/kg/h (P less than .05). Minute ventilation significantly increased and PCO2 significantly decreased as the doxapram dosage was increased (P = .02). Terminal elimination half-life was 9.9 +/- 2.9 hours. When doxapram is used for treatment of refractory neonatal apnea the starting dosage should be no more than 0.5 mg/kg/h. PMID- 3110730 TI - Neisseria meningitidis bacteremia in children: quantitation of bacteremia and spontaneous clinical recovery without antibiotic therapy. AB - The relationship between the magnitude of bacteremia due to Neisseria meningitidis and the clinical diagnosis was determined for 43 children who had fever in the presence or absence of focal signs of infection. Bacteremia was quantitated by the previously described procedure using heparinized blood (0.2 to 1.0 mL). Additionally, blood was cultured by means of the radiometric Bactec technique. Seventeen patients had meningitis, 12 had meningococcemia, 13 had unsuspected or "occult" bacteremia, and five had other diagnoses. "Occult" bacteremia was diagnosed initially in four patients, but subsequently meningitis was diagnosed. All 13 patients with 500 or more organisms per milliliter had meningitis or meningococcemia in contrast to 12 (55%) of 22 patients with less than 500 organisms per milliliter (P less than or equal to .0035). Only 18 (42%) of these patients bacteremic with N meningitidis presented with petechiae or purpura. All 13 children with occult bacteremia were sent home after blood cultures were obtained; six of the 13 received a regimen of oral amoxicillin for otitis media. At reexamination (interval 16 to 119 hours) four had meningitis, seven were clinically improved (afebrile, negative blood culture, without invasive disease), and two were still mildly febrile with negative blood culture. Three of these bacteremic children experienced spontaneous clinical and bacteriologic resolution without antibiotic treatment. This has not been previously reported. PMID- 3110731 TI - [Acute-phase response of the body (theoretical aspects and clinical significance)]. PMID- 3110732 TI - [Acid-base status in bronchial asthma in children]. PMID- 3110733 TI - Pathology of neonatal surfactant deficiency. PMID- 3110734 TI - The effects of CO2 and fixed acid on the O2-Hb affinity of rabbit and cat blood. AB - The action of respiratory and metabolic acid-base disturbances on the O2-Hb affinity was studied in rabbits and cats. Blood samples of both species were exposed to in vitro pH-changes, which were either achieved by variation of PCO2 (2.8-8.3 kPa) at constant lactic acid concentration, or by addition of lactic acid (5-14 mmol X 1(-1) at constant PCO2. The PO2 at halfsaturation (P50) and the Hill's n were determined from O2-Hb dissociation curves (ODC) in a range between 20 and 80% SO2. Under standard conditions (T = 311 K, PCO2 = 5.33 kPa, pH = 7.4), the average P50 value was 4.66 +/- 0.05 kPa in rabbits, that is slightly higher than reported by others, and 5.17 +/- 0.03 kPa in cats. The average values of Hill's n were 2.91 +/- 0.02 and 2.95 +/- 0.03 for rabbits and cats, respectively. When plasma pH was varied by CO2, the resulting classical CO2 Bohr factor phi CO2 = delta lgP50/delta pH50 was distinctly higher in cats (-0.560 +/- 0.006, n = 25) than in rabbits (-0.504 +/- 0.014, n = 22), although in the latter species being even higher than reported elsewhere. Concomitant metabolic acidosis did not significantly affect phi CO2, but shifted the P50 at a given plasma pH to lower values. Substitution of lactic acid with equimolar amounts of sodium lactate left both phi CO2 and P50 unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110735 TI - Effects of sodium on the calcium paradox in rat hearts. AB - Reduction of the Na concentration in the Ca-free perfusion solution reduces the amount of myoglobin released by the cells when Ca is readmitted if sucrose is used to replace NaCl under mild hypothermia. When salts like cholinechloride or LiCl are used instead of sucrose, no protection is seen at any temperature. The temperature threshold above which myoglobin loss sharply increases is lowered by prolonged Ca depletion or by the addition of EGTA to the Ca-free solution. Protection by sucrose does not occur in the presence of EGTA. An increase of cell Na induced by strophanthidin during the Ca depletion phase has no effect on myoglobin release. The exponential decline in twitch tension in the early phase of Ca deprivation has the same half-live (T1/2) for Ca-free solutions containing 145 mM Na or 35 mM Na (110 mM Li or choline), but its T1/2 is prolonged if sucrose is used to replace NaCl. When 5 mM EGTA is added to the Ca-free solutions, the T1/2 is shortened and is not changed by the replacement of NaCl with sucrose. The rate of washout of Ca within the first 20 s of Ca depletion has a similar time course in a normal Na or in a Li and low Na solution. In a sucrose and low Na solution the rate of the Ca efflux is reduced. The addition of EGTA increases this rate and abolishes the slowing effect of a sucrose and low Na solution. Therefore myoglobin release during the Ca paradox does not depend on the Na gradient across the sarcolemma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110736 TI - Effects of glutaraldehyde fixation on renal tubular function. I. Preservation of vasopressin-stimulated water and urea pathways in rat papillary collecting duct. AB - Using the in vitro microperfusion technique on isolated rat papillary collecting duct (PCD), we examined whether the glutaraldehyde-fixation method can be also applied to the mammalian collecting duct for preservation of the vasopressin stimulated water and urea transport. Arginine vasopressin (AVP) at 10(-9) mol/l increased diffusional water permeability (Pdw) from 101.9 +/- 10.76 to 283.3 +/- 16.67 X 10(-7) cm2 s-1 (n = 8, P less than 0.01) and urea permeability (Purea) from 30.3 +/- 2.24 to 83.5 +/- 7.80 X 10(-7) cm2 s-1 (n = 8, P less than 0.01). Both parameters remained elevated after fixation with 0.1 mol/l glutaraldehyde even in the absence of AVP, with the values being 265.0 +/- 14.47 and 74.5 +/- 7.15 X 10(-7) cm2 s-1, respectively. Glutaraldehyde fixation did not affect the basal levels of Pdw or Purea. Phloretin at 2.5 X 10(-4) mol/l decreased glutaraldehyde-fixed AVP-stimulated Purea from 79.0 +/- 7.96 to 29.7 +/- 3.66 X 10(-7) cm2 s-1 (n = 4, P less than 0.01) and from 73.2 +/- 7.05 to 38.7 +/- 3.53 X 10(-7) cm2 s-1 (n = 4, P less than 0.01) when the drug was added to the lumen or to the bath, respectively. Phloretin also decreased glutaraldehyde-fixed non stimulated Purea by 25-40%. However, this drug did not affect glutaraldehyde fixed Pdw. These findings indicate that the glutaraldehyde fixation method can be applied to mammalian collecting tubules for studying vasopressin stimulated Pdw and Purea. Purea fixed by glutaraldehyde is functionally flexible and may be distinct from the water pathway. PMID- 3110737 TI - Effect of glutaraldehyde on renal tubular function. II. Selective inhibition of Cl- transport in the hamster thin ascending limb of Henle's loop. AB - In order to further characterize Cl- transport of the thin ascending limb of Henle's loop (TAL), we observed the effects of glutaraldehyde on Na+ and Cl- transport in hamster TAL perfused in vitro. We found that 0.1 mol/l glutaraldehyde added either to the lumen or to the bath caused a rapid irreversible reversal of the NaCl diffusion potential. This was mainly accounted for by an inhibition of Cl- permeability (10(-7) cm2 s-1) from 93.51 +/- 8.39 to 14.89 +/- 3.91 (P less than 0.01, n = 9). By contrast, Na+ permeability changed little from 34.18 +/- 3.27 to 26.56 +/- 2.74 (P less than 0.01, n = 6). Glutaraldehyde treatment abolished the halogen-permselectivity of the TAL as determined by the voltage deflection seen upon ionic substitution. Permeabilities for Cl-, Br-, I-, and SCN- relative to Na+ were changed from 3.16 +/- 0.20, 3.22 +/- 0.19, 2.97 +/- 0.26 and 4.36 +/- 0.36 to 0.38 +/- 0.07, 0.35 +/- 0.06, 0.36 +/- 0.07 and 0.58 +/- 0.05, respectively. The effect of glutaraldehyde on the NaCl diffusion potential was dose-dependent in the range from 10(-5) to 10(-1) M. The effect was reversible at concentrations lower than 10(-3) M. Glutaraldehyde did not affect the NaCl diffusion potential of the long-loop descending limb. These observations constitute additional evidence that the mechanism of Cl- transport across the TAL is different from that of Na+ transport. Glutaraldehyde might inhibit Cl- transport in the TAL by cross-linking amino acid residues of the proteins essential for halogen transport across this segment. PMID- 3110738 TI - Non-electrolyte transport across renal proximal tubule cell membranes measured by tracer efflux and light scattering. AB - Non-electrolyte transport in brush border membrane vesicles (BBMV), basolateral membrane vesicles (BLMV) and in viable cells isolated from the proximal convoluted tubule (PCT) of the rabbit kidney were measured by rapid filtration and stopped-flow light scattering techniques. Efflux of tracer solute was measured by loading packed vesicles or cells with 14C solute, diluting into nonradioactive buffer and filtering rapidly at varying incubation times. In BBMV at 23 degrees C, [14C-urea] decreased exponentially with time constant 3.2 +/- 0.3 s (S.D., n = 5) corresponding to a permeability coefficient (Purea) of 1.6 X 10(-6) cm/s, assuming a BBMV surface-to-volume ratio of 2 X 10(5) cm-1. Purea decreased to 7 X 10(-7) cm/s in the presence of 20 mM phenylurea. Tracer efflux determinations of BBMV Purea (1.6 X 10(-6) cm/s) and Pglycerol (0.6 X 10(-6) cm/s), and BLMV Purea (1.8 X 10(-6) cm/s) and Pthiourea (2.5 X 10(-6) cm/s) were in excellent agreement with Ps values determined by stopped-flow light scattering, where the time course of vesicle volume (linearly related to scattered light intensity) was measured in response to 100 mM outwardly directed solute gradients. These results establish accurate Ps value in brush border and basolateral membranes and support the application of light scattering to measure Ps in vesicles. In PCT cells however, there were systematic differences in urea and thiourea transport measured by tracer efflux and light scattering, indicating the potential difficulties in applying light scattering to Ps measurements in complex cell systems. PMID- 3110739 TI - [Peptic ulcer in Norway--a health economics evaluation]. PMID- 3110740 TI - Preparation of base-modified nucleosides suitable for non-radioactive label attachment and their incorporation into synthetic oligodeoxyribonucleotides. AB - A very mild and efficient procedure has been developed for the preparation of C-5 substituted deoxyuridines. The substituent carries a masked primary aliphatic amino group. These compounds are readily converted into their phosphoramidites and can be used to prepare oligonucleotides carrying one or more aliphatic amino groups. Fluorescein isothiocyanate coupled to these compounds gives oligonucleotide probes carrying multiple fluorescein labels. These compounds have a free 5'-hydroxy group enabling additional 5'- end radioactive labelling for evaluation of their hybridization characteristics. It was found that oligonucleotides carrying a long (11 atom) linker arm to the fluorescein hybridize more efficiently to mRNA than those carrying a short (4 atom) arm. The long linker arm derivatives are comparable to underivatized oligonucleotides in hybridizing to mRNA. PMID- 3110742 TI - The nucleotide sequence of 3-isopropylmalate dehydrogenase gene from Bacillus subtilis. PMID- 3110743 TI - Drosophila Cu-Zn superoxide dismutase cDNA sequence. PMID- 3110741 TI - N segment insertion and region-directed somatic hypermutation in a kappa gene of a t(2;8) chromosomal translocation. AB - A detailed molecular analysis of both reciprocal recombination products of the variant t(2;8) chromosomal translocation of the Burkitt lymphoma derived cell line JI and their germline counterparts was carried out. The breakpoint on chromosome 8 is localized 28 kb to the 3' side of the c-myc protooncogene, the breakpoint on chromosome 2 was found to be within an aberrantly rearranged VK gene (abbreviations ref. 1). Novel features of the immunoglobulin moiety involved in this process include insertion of extra nucleotides in the V-J junction which have the characteristics of a N segment as it has been found up to now only in heavy chain and T cell receptor genes; the occurrence of somatic mutations in 8q+ and not in 2p-. These data allow a reconstruction of the course of events in the cell line JI; remarkable sequence regularities at the chromosomal breakpoints consisting of symmetrically placed dinucleotides and elements related to the hepta- and nonanucleotide recombinase recognition sequences are discussed in the context of the translocation mechanism. PMID- 3110744 TI - [Evaluation of the results of the treatment of testicular seminoma irradiated by the megavolt technic]. PMID- 3110745 TI - [Post-radiation carditis in a patient treated for teratocarcinoma of the mediastinum]. PMID- 3110746 TI - Melanoma and dietary lipids. AB - Samples of subcutaneous adipose tissue were taken from 100 melanoma patients and 100 matched controls in Sydney in 1984-1985 and were analyzed for constituent fatty acids. The mean percentage of linoleic acid in the triglycerides of the subcutaneous adipose tissue (PLASAT) of these subjects was substantially higher than that in a similar group examined in 1975-1976. In addition, the percentage of polyunsaturated fatty acids was found to be higher in the melanoma patients than in the controls (p less than 0.01), and there were significantly more controls than patients who had a low PLASAT (p less than 0.01). Relevant literature is quoted and the suggestion is made that increased consumption of dietary polyunsaturates may have a contributory effect in the etiology of melanoma. PMID- 3110747 TI - Cost-effective tertiary care. AB - We have highlighted several key points: There is a discrete subgroup of psychiatric patients who benefit from tertiary care. This treatment demands extraordinary intensity of staffing within the context of a facility whose leadership (and ownership) is committed to that level of care. Treatment should optimally occur within small residential units with clinically homogeneous populations of defined age range. mechanisms of quality control, including extensive programs of orientation, inservice, and utilization review, are paramount in achievement of success. Financial feasibility is dependent on maintenance of a high rate of occupancy, which in turn is reflective of the facility's effectiveness in fulfillment of its clinical mandate. Financial feasibility is dependent on a low relapse rate. Integration of biologic, psychologic antisocial aspects of treatment is the key to effectiveness. An intensively staffed and well-integrated unit is essential. PMID- 3110748 TI - Long-term psychoanalytic hospital treatment of adolescents. AB - Approximately 0.5 per cent of adolescents require long-term hospital treatment to remedy their severe personality disorder or psychosis. This article describes the treatment processes that are used in psychoanalytic hospitals to restore more normal personality functioning. The concepts that guide these treatment processes are the resolution of early developmental conflicts, working through the transference to the institution, providing positive support, containment, and re education. PMID- 3110749 TI - Use of a long-term inpatient unit as a site for learning psychotherapy. AB - Little has been written about the benefits of a long-term inpatient unit as a site for training psychiatric residents to do psychoanalytically-oriented psychotherapy. An account is provided of the General Clinical Research Service at the New York State Psychiatric Institute, a unit that is structured to provide residents with this type of learning experience, which is described at length. Emphasis is placed on how the rotation is designed to ensure that residents learn affectively and experientially as well as intellectually. PMID- 3110750 TI - Pancreatic exocrine aplasia, clinical features of leprechaunism, and abnormal gonadotropin regulation. AB - A female infant displaying morphological and clinical abnormalities is described. She had severe developmental delay, intrauterine growth retardation, and failure to thrive. Her features included an elfin facies, body and facial hirsutism, buttonlike nipples and prominent clitoris and labia. Endocrinological evaluation revealed markedly elevated serum gonadotropin levels. An LHRH stimulation test showed no LH response to LHRH but a rapid and pronounced FSH response. The patient died at 13 months following a respiratory infection. Postmortem examination revealed normal pituitary histology but an unusual pancreatic histology characterized by total absence of acinar cells. This patient had features suggestive of several clinical syndromes including leprechaunism, Shwachman syndrome, and Johanson-Blizzard syndrome, none of which, was completely satisfied. It is concluded that the infant may represent an atypical case of leprechaunism or a previously undescribed syndrome. PMID- 3110751 TI - Differential diagnosis of unusual skin diseases in infants. AB - There are a number of relatively unique clinical skin diseases that may develop on the buttocks of infants. These include iatrogenic skin diseases caused by external medicine; skin tumors caused by methylrosaniline chloride (Pyoktanin); atrophy of the skin due to steroidal liniments; nevus and tumor diseases, such as nevoxanthoendothelioma and Letterer-Siwe disease. Finally, there is chronic granulomatous disease. These unusual cases are reviewed and their differential diagnoses discussed. PMID- 3110752 TI - [Biology of the infectious scrapie agent]. PMID- 3110753 TI - Immunopathology of Hodgkin's disease. AB - The past several years have seen major advances in the immunopathology of Hodgkin's disease, although the cell of origin remains unproven. Reed-Sternberg cells have been characterized with monoclonal antibodies and are found to consistently express panleukocytic antigen (T-200), HLA-DR antigens, and several activation-proliferation antigens (Tac, OKT-9, Ki-1). Reed-Sternberg cells also express a nonlineage-specific antigen defined by the antigranulocyte antibody Leu M-1. Lineage-specific B, T or monocyte-macrophage antigens are generally lacking. With the possible exception of the lymphocyte predominant form of the disease, Hodgkin's disease appears immunologically homogeneous. The possible origin of Reed-Sternberg cells by neoplastic transformation of antigen-presenting dendritic cells (interdigitating reticulum cells) appears to be an attractive albeit unproven hypothesis. Application of molecular biologic techniques in the future may yield definitive evidence as to the origin and nature of these enigmatic cells, and to the pathophysiology of the disease which they define. PMID- 3110754 TI - Rheumatoid factors in human autoimmune disease: their origin, development and function. PMID- 3110756 TI - Experimental models of type-I diabetes. PMID- 3110755 TI - Complement activation in extracorporeal circulation: physiological and pathological implications. PMID- 3110757 TI - [Solitary pulmonary coin lesion as a manifestation of light chain plasmacytoma of the kappa type]. PMID- 3110758 TI - [Successful treatment of a most severe therapy-refractory status asthmaticus by extracorporeal CO2 elimination]. PMID- 3110759 TI - A novel method of electrophoresis for the separation of individual human serum glycoproteins. AB - A method for the isolation of protein components by a combination of polyacrylamide gel electrophoresis and electro-extraction of slices of gel contained in cellophane dialysis tubing, using the H tube electrophoresis apparatus, is described. The method was applied to the purification of individual human serum glycoproteins. Although the glycoproteins have widely differing electrophoretic mobilities, they appeared to be antigenically interrelated judging from their complex "spurring" in Ouchterlony double gel diffusion tests. PMID- 3110760 TI - Facile preparation and some applications of an affinity matrix with a cleavable connector arm containing a disulfide bond. AB - A versatile affinity matrix in which the ligand of interest is linked to the matrix through a connector arm containing a disulfide bond is described. It can be synthesized from any amino-substituted matrix by successive reaction with 2 imino-thiolane, 5,5'-dithiobis(2-nitrobenzoic acid), and a thiol derivative of the ligand of choice. The repertoire of ligands can be significantly increased by the appropriate use of avidin-biotin bridges. After adsorption of the material to be fractionated, elution can be effected by reducing the disulfide bond in the connector arm with dithiothreitol. Examples of the preparation and use of various affinity matrices based on amino-substituted Sepharose 6MB are given. One involves the immobilization of the Fab' fragment of a monoclonal antibody against Aspergillus oryzae beta-galactosidase and the specific binding of that enzyme to the resulting immunoaffinity matrix. Another involves the immobilization of N biotinyl-2-thioethylamine followed by complex formation with avidin. The resulting avidin-substituted matrix was used for the selective adsorption and subsequent recovery of mouse hybridoma cells producing anti-avidin antibodies. By further complexing the avidin-substituted matrix with appropriate biotinylated antigens, it should be possible to fractionate cells producing antibodies against a variety of antigens. PMID- 3110761 TI - [Experience with the treatment of children with diabetes mellitus using allo- and xenografts of cultures of pancreatic islet cells]. AB - The paper is concerned with the study of the results of allo- and xenotransplantation of pancreatic islet cell culture to 44 children aged 1.5 to 15 suffering from a severe form of insulin dependent diabetes mellitus. An impossibility to achieve stable compensation of disease with routine therapy and complications of diabetes mellitus were the main indications for transplantation. Transplantation of beta-cell culture can be recommended as one of the methods of adjuvant therapy of juvenile diabetes. PMID- 3110762 TI - [Role of the time factor in the pancreatic and extrapancreatic mechanisms of action of glibenclamide]. AB - A study was made of the effect of short- and long-term administration of one of the sulfanilurea derivatives of the 2nd generation--glibenclamide on pancreatic beta-cell function and the sensitivity of peripheral tissues to insulin under clinical and experimental conditions. The authors established time correlation of the mechanisms of glibenclamide hypoglycemic action: beta-cytotropic action in acute administration of the drug and extrapancreatic influence in chronic administration. An idea of predominant significance of the postreceptor level in the realization of the extrapancreatic effect of long-term administration of glibenclamide was substantiated. PMID- 3110763 TI - [Relation between antibody formation and drug resistance of Mycobacterium tuberculosis]. PMID- 3110764 TI - [Immunological indices of patients with destructive pulmonary tuberculosis due to bovine and human Mycobacterium tuberculosis]. PMID- 3110765 TI - [Significance of different Mycobacterium species in the epidemiology of tuberculosis]. PMID- 3110766 TI - [Characteristics of a Mycobacterium population growing in pulmonary tuberculomas]. PMID- 3110767 TI - [Etiological characteristics of bacterial and viral pneumonias in children and adults]. PMID- 3110768 TI - Cell autonomy of expression of neurogenic genes of Drosophila melanogaster. AB - In embryos of Drosophila melanogaster the development of a pluripotent cell in the neurogenic ectoderm as a member of either a neural or an epidermal lineage depends on its interactions with neighboring cells. Certain genes, designated neurogenic, participate in this process in that there is a deficiency of epidermal histotypes in mutant embryos lacking neurogenic gene functions. To test the cell autonomy of expression of the neurogenic phenotype, individual cells were transplanted from the neurogenic ectoderm of mutant donor embryos into wild type host embryos. Cells transplanted from donors homozygous for any of several mutant alleles of the neurogenic genes amx, N, bib, mam, neu, and Dl were found to give rise to clones exhibiting a distribution of neural and epidermal histotypes similar to that of the wild type. By contrast, cells transplanted from donors homozygous for loss of the neurogenic E(spl) gene gave rise exclusively to clones of neural histotypes. Thus, only the expression of E(spl) is autonomous, with that of all of the other tested neurogenic genes being nonautonomous. These results are consistent with the inference that the nonautonomous genes provide a source and the autonomous gene provides a receptor of a hypothetical intercellular regulatory signal that is necessary for cell commitment to an epidermal rather than neural fate. PMID- 3110769 TI - Inhibition of development in Myxococcus xanthus by monoclonal antibody 1604. AB - Monoclonal antibody (mAb) 1604 is directed against a cell surface antigen of Myxococcus xanthus. Purified antibody 1604 inhibited development of M. xanthus under conditions of submerged culture procedure otherwise leading to fruiting body formation. Intact molecules of mAb 1604, as well as its Fab fragments, inhibited developmental aggregation, autolysis, fruiting body formation, and sporulation. The addition of relatively small amounts of antibody every 4 hr was much more effective than a single large dose given at the onset of development. The inhibitory action of mAb 1604 on development was reversible after prolonged incubation of the antibody with cells; this was probably due to proteolytic degradation of the antibody. The effect of mAb 1604 on submerged bacterial development was neutralized by affinity-purified 1604 cell surface antigen. Another antibody, mAb 2788, directed against an M. xanthus cell surface antigen, did not block development. These data suggest that 1604 cell surface antigens is involved in contact-mediated cell interactions in M. xanthus. PMID- 3110770 TI - Genetic instability in Drosophila melanogaster: cytogenetic analysis of MR induced X-chromosome deficiencies. AB - We present data that demonstrate that three MR elements isolated from wild populations of Drosophila melanogaster on two continents can cause large deletions of the X chromosome in males. The deleted chromosomes, termed mini-X chromosomes, are induced at a frequency of approximately 1:4000 in chromosomes that are initially free of P elements. In situ hybridizations using a cloned P sequence as a probe fail to reveal any sequences homologous to the nomadic P family at the deletion breakpoints. Genetic analysis of 12 such mini-X chromosomes also reveals that there are no "hotspots" of chromosome breakage and that there must have been a minimum of three distinct distal breakpoints and five different proximal breakpoints in the formation of these deleted chromosomes. In fact all 12 proximal and 12 distal breakpoints may well be unique. Our data show that MR elements generate essentially random breaks along the X chromosome. We emphasize that we find no involvement of P sequences in the chromosome breakage process, consonant with the notion that MR elements exert their influence on processes involved in mitotic crossing-over. PMID- 3110771 TI - Induction of cytotoxicity in resting human T lymphocytes bound to tumor cells by antibody heteroconjugates. AB - An in vitro model for peripheral human T-cell activation and resultant tumor cell killing is described. Cytotoxic T lymphocytes may be generated from resting lymphocytes by incubation of human peripheral blood mononuclear cells for 3 days with the anti-CD3 monoclonal antibody OKT3. Cytotoxicity in peripheral blood mononuclear cells can also be induced by adding an anti-target-OKT3 antibody conjugate and 10% (vol/vol) fetal calf serum to the culture medium. Conjugate activation of T cells was almost completely blocked, however, when 20% (vol/vol) human serum was added to the medium. Conjugate-mediated peripheral blood mononuclear cells activation was restored to some extent by the addition of melanoma target cells to the culture and was markedly enhanced by a second conjugate containing anti-target cell and anti-CD28 antibody. Monoclonal antibody 9.3 (anti-CD28) provides a progression signal in T-lymphocyte activation when used in combination with anti-CD3. Thus, presentation by the tumor target cells of anti-CD3 and anti-CD28 to resting human lymphocytes causes T-cell activation, which is independent of monocytes, proceeds in the presence of human serum, and results in tumor cell killing. PMID- 3110772 TI - Secretion of follicle-stimulating hormone and production of inhibin are reciprocally related. AB - The production of inhibin in cultured granulosa cells from immature hypophysectomized, estrogen-treated rats and Sertoli cells from normal animals was determined by a specific radioimmunoassay using an antiserum against a synthetic replicate of [Tyr30]inhibin alpha-chain-(1-30). The amount of immunoreactive inhibin detected in the spent media of these cells is in proportion to the density of cells plated and the concentration of exogenously added follicle-stimulating hormone (FSH). In the presence of the estrogen precursor androstenedione (10(-7) M), FSH, but not luteinizing hormone, produced a dose-dependent increase in inhibin during 2-day culture of granulosa cells. In the absence of the estrogen precursor, similar but somewhat diminished inhibin production in responding to FSH was observed. Exogenously added estrogen potentiated the FSH-mediated release of inhibin in the absence of androstenedione. Neither androstenedione nor estradiol added to the cultured Sertoli cells had effect on inhibin production. A preparation of pure inhibin isolated on the basis of an in vitro bioassay and characterized chemically specifically suppressed serum FSH but not luteinizing hormone, when it was injected (24 micrograms per injection, two injections) into acutely ovariectomized rats. Thus, inhibin secreted by the granulosa and Sertoli cells specifically suppresses the secretion of pituitary FSH, and in turn FSH is primarily responsible for the inhibin production in these gonadal cells, as in a classical negative-feedback relationship. PMID- 3110773 TI - Complete cDNA and derived amino acid sequence of human factor V. AB - cDNA clones encoding human factor V have been isolated from an oligo(dT)-primed human fetal liver cDNA library prepared with vector Charon 21A. The cDNA sequence of factor V from three overlapping clones includes a 6672-base-pair (bp) coding region, a 90-bp 5' untranslated region, and a 163-bp 3' untranslated region within which is a poly(A) tail. The deduced amino acid sequence consists of 2224 amino acids inclusive of a 28-amino acid leader peptide. Direct comparison with human factor VIII reveals considerable homology between proteins in amino acid sequence and domain structure: a triplicated A domain and duplicated C domain show approximately equal to 40% identity with the corresponding domains in factor VIII. As in factor VIII, the A domains of factor V share approximately 40% amino acid-sequence homology with the three highly conserved domains in ceruloplasmin. The B domain of factor V contains 35 tandem and approximately 9 additional semiconserved repeats of nine amino acids of the form Asp-Leu-Ser-Gln-Thr-Thr/Asn Leu-Ser-Pro and 2 additional semiconserved repeats of 17 amino acids. Factor V contains 37 potential N-linked glycosylation sites, 25 of which are in the B domain, and a total of 19 cysteine residues. PMID- 3110774 TI - Sequence and evolution of HLA-DR7- and -DRw53-associated beta-chain genes. AB - cDNA clones representing products of the DR7 and DRw53 beta-chain genes were isolated from the human B-lymphoblastoid cell line MANN (DR7,DRw53,DQw2, DPw2). The DRw53 beta sequence was identical to a DRw53 beta sequence derived from cells with a DR4 haplotype. In contrast, the DR7 beta sequence was as unrelated to DR4 beta sequence as it was to other DR beta-related genes, except at the 3' untranslated region. These results suggest that the DR7 and DR4 haplotypes may have been derived relatively recently from a common ancestral haplotype and that the DR4 and DR7 beta-chain genes have undergone more rapid diversification in their beta 1 domains, most probably as a result of natural selection, than have the DRw53 beta-chain genes. Short tracts of sequence within the DR7 and DRw53 beta 1 domains were shared with other DR beta sequences, indicating that exchanges of genetic information between beta 1 domains of DR beta-related genes have played a part in their evolution. Serological analysis of mouse L-cell transfectants expressing surface HLA-DR7 molecules, confirmed by antibody binding and allelic sequence comparisons, identified amino acid residues that may be critical to the binding of a monomorphic DR- and DP-specific monoclonal antibody. PMID- 3110775 TI - High rates of deletions in the constant region segment of the immunoglobulin mu gene. AB - Spontaneous deletions at the immunoglobulin heavy-chain locus are frequently found in myelomas, hybridomas and pre-B-cell lines. We have measured the rates for large and small deletions within the constant-region gene segment for mu chain in a pre-B-cell lines. The large deletions, which include the entire first and second exons, occurred at a rate of 1.7 X 10(-5) per cell generation. The small deletions, which span a few base pairs, occurred at a rate of 1.4 X 10(-7) per cell generation. The rate for the reversion of a termination codon in the second exon is even less than that for the small deletions and is 1000 times lower than the reversion rate that had been determined for the variable-region gene segment. Therefore, the variable-region gene segment is likely to be the preferred target for hypermutation. PMID- 3110776 TI - High-frequency deletional rearrangement of immunoglobulin kappa gene segments introduced into a pre-B-cell line. AB - We describe an immunoglobulin gene recombination indicator in which a specific rearrangement via deletion results in the acquisition of a dominant phenotype. The indicator consists of the Escherichia coli xanthine/guanine phosphoribosyltransferase (gpt) gene, whose translation is prevented by the presence of an upstream initiation codon out of frame with respect to the gpt coding sequence. Flanking this barrier initiation codon are the heptamer-spacer nonamer recognition sequences from a kappa chain variable region (V kappa) and from a kappa chain joining region (J kappa). A proper V-J joint results in the deletion of the translational barrier and allows expression of the selectable marker. When tested by transfection into fibroblasts, no rearrangements were detected and the presence of the barrier initiation codon was sufficient to completely abolish gpt expression in these cells. Similarly, no rearrangements were detected after transfer of the test gene into myeloma cells. However, when the construct was introduced into the pre-B-cell line 38B9, greater than 80% of the transfected cells showed evidence of a specific rearrangement. These rearrangements were associated with the translation of gpt, although no selection for its expression was needed. DNA sequence analysis of six different V-J joints revealed that the rearrangement proceeded with a high degree of accuracy. These results indicate that only very minimal DNA sequences (21 base pairs 5' of the V heptamer and 4 base pairs 3' of its nonamer; less than 45 base pairs 5' of the J nonamer and 3' of its heptamer) are required for efficient rearrangement and provide formal proof that kappa gene segments can rearrange by a deletional mechanism. PMID- 3110777 TI - Transformation of Corynebacterium diphtheriae, Corynebacterium ulcerans, Corynebacterium glutamicum, and Escherichia coli with the C. diphtheriae plasmid pNG2. AB - The transfection and transformation of members of two species of pathogenic corynebacteria, Corynebacterium diphtheriae and Corynebacterium ulcerans, is described. Protoplasts were produced by treatment with lysozyme following growth in glycine, and a medium was defined on which a significant fraction of the osmotically sensitive cells were regenerated. Transfections were carried out with DNA from corynephage 782, a member of the beta family of converting phages, and transformations were performed with DNA of plasmid pNG2, a 9500-kDa plasmid that was isolated from an erythromycin-resistant strain of C. diphtheriae and carries the resistance gene. Strains of Corynebacterium glutamicum and Escherichia coli were also successfully transformed with pNG2 DNA. Transfection frequencies were in the range of 3-8 X 10(3) plaque-forming units/micrograms of phage DNA, and transformation frequencies were in the range of 0.2-150 colony-forming units/micrograms of plasmid DNA. Plasmid pNG2 replicated and was stably maintained in all transformants both in the presence or absence of erythromycin. Thus, it displayed the ability to replicate in strains of both Gram-positive and Gram-negative bacteria without the intervention of genetic engineering. pNG2 DNA isolated from any of the transformed strains was able to transform all parental strains. The host range of pNG2 suggests its possible utility in or as a shuttle vector for the study and manipulation of genes from corynebacterial strains of animal origin. PMID- 3110778 TI - Characterization of c-Ki-ras oncogene alleles by direct sequencing of enzymatically amplified DNA from carcinogen-induced tumors. AB - Activated c-Ki-ras genes in liver tumors from rats exposed to the potent hepatocarcinogen aflatoxin B1 were analyzed to determine the nature of their activation by characterization of two c-Ki-ras alleles present in tumor-derived NIH 3T3 mouse transformants. Using selective hybridization of synthetic oligonucleotides to transformant DNA, we have determined that a single G X C to A X T base transition in either the first or second position of the 12th codon is associated with activation of the gene. Such mutations would lead to amino acid substitutions of aspartate or serine for glycine in the mutant proteins. To confirm these findings, we applied a technique for direct sequence analysis of a 90-base-pair region of the rat c-Ki-ras gene produced by primer-directed enzymatic amplification. Findings produced by this approach, which provides a convenient method to characterize mutations in multiple alleles without the necessity to clone individual genes, confirmed the presence and identity of the 12th codon mutations in the activated oncogene, as initially determined by the oligonucleotide hybridization technique. PMID- 3110779 TI - Detection of normal B-cell precursors that give rise to colonies producing both kappa and lambda light immunoglobulin chains. AB - The pre-B-cell cloning assay is an in vitro differentiation system in which B lymphocyte precursors expand and generate colonies containing immunoglobulin secreting cells. Analysis of surface characteristics, growth requirements, and kinetics suggested that these cells represent early stages of the B-cell differentiation pathway. Here we describe a modification of the assay, which allowed us to determine the differentiative potential of these clonable pre-B cells. Using a nitrocellulose protein-transfer technique, we studied immunoglobulin light chain expression in colonies derived from fetal mouse liver B-cell precursors; in particular, we explored whether the B-cell precursors are already committed to the expression of a particular light chain gene at the initiation of culture. Our results show that fetal liver-derived B-cell progenitors generate colonies in vitro that secrete kappa and lambda light chains at a ratio similar to that found in colonies derived from adult splenic B cells. Further, we document the existence of colonies that are derived from single cells and that simultaneously secrete both types of light chains. This indicates that the progenitors of (kappa + lambda)-producing colonies are light chain uncommitted at the initiation of culture. These cells are able to rearrange their light chain genes in vitro and differentiate along the B-cell pathway to form colonies secreting both kappa and lambda chains. PMID- 3110780 TI - Cloning of human thymic subcapsular cortex epithelial cells with T-lymphocyte binding sites and hemopoietic growth factor activity. AB - The thymic microenvironment involves complex cell interactions among different types of epithelial cells, macrophages, tissue histiocytes, and immature and maturing T cells. We describe the isolation of a subset of thymic epithelial cells by selective primary culture followed by cotransfection with a simian virus 40 replication-origin-defective mutant and pSV2neo plasmid. The cloned cells have the composite immunophenotype that is unique to thymic subcapsular epithelial cells, suggesting that they may provide a model system in vitro for analyzing the earliest steps in T-cell differentiation. This possibility is supported by the finding that these epithelial cells express LFA-3-associated binding sites for T cells, secrete a macrophage hemopoietic growth factor, and synergize with macrophages in the production of interleukin 1. PMID- 3110781 TI - Platinum-DNA adducts in leukocyte DNA correlate with disease response in ovarian cancer patients receiving platinum-based chemotherapy. AB - Fifty-five ovarian cancer patients receiving platinum drug-based chemotherapy have been studied prospectively to determine the extent of formation of the bidentate intrastrand adducts of diammineplatinum covalently attached to the N7 positions of adenosine and/or guanosine in leukocyte DNA. Data for clinical response, obtained from medical records, were then correlated with the adduct values. Patients were treated with platinum-based single-agent or combination chemotherapy containing cis-diamminedichloroplatinum (II) or diamminecyclobutane dicarboxylatoplatinum on approved experimental protocols. Adduct measurements were performed by ELISA, and disease response to therapy was assessed by standard oncologic criteria. This study comprises a total of 101 blood samples obtained after intravenous cis-diamminedichloroplatinum (II) or diamminecyclobutane dicarboxylatoplatinum infusion from 55 individuals, and in each case the highest (or "peak") adduct level for each patient was chosen for statistical analysis. Values for median adduct levels in patients grouped by complete response, partial response, and no response were 212, 193, and 62 amol of adduct per microgram of DNA, respectively. Analysis of these data by Jonckheere's test (an extension of the Mann-Whitney test) shows that higher levels of adduct formation correlates with disease response with a two-sided P value of 0.030. Of eight patients on single-agent therapy whose buffy-coat samples did not have measurable adduct levels, none responded to therapy. Analysis of these data using the exact test for trend shows that the formation of adduct at a level of 160 amol/micrograms of DNA or greater correlates with disease response with a two-sided P value of 0.032. Thus in ovarian cancer patients, the formation of the intrastrand diammineplatinum adducts in leukocyte DNA is associated with favorable disease response to cis-diamminedichloroplatinum (II) or diamminecyclobutane dicarboxylatoplatinum chemotherapy. PMID- 3110782 TI - Interferon messenger RNA is produced constitutively in the organs of normal individuals. AB - The use of RNA blot hybridization with DNA or RNA probes of high specific activity has shown that interferon (IFN)-alpha mRNA is present constitutively in the spleen, kidney, liver, and peripheral blood leukocytes of normal individuals. A single band (approximately equal to 1.2 kilobases) was detected in poly(A)+ RNA isolated from human organs. This RNA hybridized specifically to human IFN-alpha 1 DNA and comigrated with mature IFN-alpha mRNA from virus-induced human peripheral blood leukocytes. No IFN-beta RNA transcripts were detected in any of the tissues tested. IFN-gamma mRNA was detected in only one sample of normal human spleen, which also contained an unusually high level of IFN-alpha mRNA. The use of a modified S1 mapping technique revealed the presence of IFN-alpha 1 and -alpha 2 transcripts only. No IFN-alpha 4, -alpha 5, -alpha 6, -alpha 7, -alpha 8, or alpha 14 transcripts were detected in the same sample. The detection, in all the samples tested, of a characteristic pattern of expression of IFN genes, different from that obtained following induction, together with the low number of transcripts present (less than or equal to 0.03 copy per cell) suggest that specific IFN genes are transcribed constitutively in vivo. PMID- 3110783 TI - Human cDNA clones for an alpha subunit of Gi signal-transduction protein. AB - Two cDNA clones were obtained from a lambda gt11 cDNA human brain library that correspond to alpha i subunits of G signal-transduction proteins (where alpha i subunits refer to the alpha subunits of G proteins that inhibit adenylate cyclase). The nucleotide sequence of human brain alpha i is highly homologous to that of bovine brain alpha i [Nukada, T., Tanabe, T., Takahashi, H., Noda, M., Haga, K., Haga, T., Ichiyama, A., Kangawa, K., Hiranaga, M., Matsuo, H. & Numa, S. (1986) FEBS Lett. 197, 305-310] and the predicted amino acid sequences are identical. However, human and bovine brain alpha i cDNAs differ significantly from alpha i cDNAs from human monocytes, rat glioma, and mouse macrophages in amino acid (88% homology) and nucleotide (71-75% homology) sequences. In addition, the nucleotide sequences of the 3' untranslated regions of human and bovine brain alpha i cDNAs differ markedly from the sequences of human monocyte, rat glioma, and mouse macrophage alpha i cDNAs. These results suggest there are at least two classes of alpha i mRNA. PMID- 3110784 TI - Enhancement of choleragen ADP-ribosyltransferase activities by guanyl nucleotides and a 19-kDa membrane protein. AB - Choleragen activates adenylate cyclase by catalyzing, in the presence of NAD, the ADP-ribosylation of Gs alpha, the stimulatory guanyl nucleotide-binding protein of the cyclase system. Kahn and Gilman [Kahn, R. A. & Gilman, A. G. (1986) J. Biol. Chem. 261, 7906-7911] identified another guanyl nucleotide-binding protein termed ADP-ribosylation factor (ARF) that stimulated this reaction. It was proposed that the toxin substrate is an ARF-Gs alpha complex and that ARF may have a physiological role in regulation of Gs alpha activity. We have found that purified ARF from bovine brain enhances not only the ADP-ribosylation of Gs alpha but also Gs alpha-independent choleragen-catalyzed reactions. These are (i) ADP ribosylation of agmatine, a low molecular weight guanidino compound; (ii) ADP ribosylation of several proteins unrelated to Gs alpha; and (iii) auto-ADP ribosylation of the toxin A1 peptide. These reactions, as well as the ADP ribosylation of ARF itself, were stimulated by GTP or stable GTP analogues such as guanyl-5'-yl imido-beta gamma-diphosphate and guanosine 5'-O-[gamma thio]triphosphate; GDP and guanosine 5'-O-[beta-thio]diphosphate were inactive. These observations are consistent with the conclusion that ARF interacts directly with the A subunit of choleragen in a GTP-dependent fashion thereby enhancing catalytic activity manifest as transfer of ADP-ribose to Gs alpha and other proteins, to the toxin A1 peptide, or to agmatine. It is tempting to speculate that ARF may be involved in regulating one or another of the ADP ribosyltransferases found in animal cells. PMID- 3110785 TI - A common origin for enzymes involved in the terminal step of the threonine and tryptophan biosynthetic pathways. AB - Comparison of the amino acid sequence of Bacillus subtilis threonine synthase with the National Biomedical Research Foundation protein sequence library revealed a statistically significant extent of similarity between the sequence of the tryptophan synthase beta chain from various organisms and that of threonine synthase. This homology in the primary structure of threonine synthase and tryptophan synthase beta chain, which catalyze the last step in the threonine and the tryptophan biosynthetic pathways, respectively, correlates well with some of their catalytic properties and indicates that they have evolved from a common ancestor. The evolutionary relationship between these enzymes supports the hypothesis that primitive enzymes possessed a broad substrate specificity and were active in several metabolic pathways. PMID- 3110786 TI - The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells. AB - There are at least two interleukin 2 (IL-2) binding peptides: one is the Mr 55,000 peptide (p55) reactive with the anti-Tac monoclonal antibody, and the other is a Mr 75,000 non-Tac IL-2 binding peptide (p75). Independently existing Tac or p75 peptides represent low-affinity IL-2 receptors, whereas high-affinity IL-2 receptors are expressed when both peptides are present and associated in a receptor complex. It has long been known that normal large granular lymphocytes (LGL) or leukemic cells from the patients with abnormal expansions of LGL can be activated by IL-2 not only to more-potent natural killer cells but also to effectors of lymphokine-activated killer (LAK) activity, although they do not express the Tac peptide. In the present study, using cross-linking methodology, we found that normal LGL and leukemic LGL from all individuals tested expressed the p75 IL-2 binding peptide but did not express the Tac peptide. These LGL leukemia cells made proliferative responses to IL-2 but required a much higher concentration than that required for the proliferation of normal phytohemagglutinin-stimulated T lymphoblasts that express high-affinity receptors. Furthermore, the addition of IL-2 to Tac-negative LGL leukemic cells augmented transcription of the Tac gene and induced the Tac peptide. Neither the IL-2-induced proliferation nor the up-regulation of Tac gene expression was inhibited by the addition of anti-Tac. These results strongly suggest that the p75 peptide is responsible for IL-2-induced activation of LGL and that the p75 peptide alone can mediate an IL-2 signal. Thus, the p75 peptide may play an important role in the IL-2-mediated immune response not only by participating with the Tac peptide in the formation of the high-affinity receptor complex on T cells but also by contributing to the initial triggering of LGL activation so that these cells become efficient natural killer and lymphokine-activated killer cells. PMID- 3110788 TI - Metabolism of 5-fluorouracil to an N-cholyl-2-fluoro-beta-alanine conjugate: previously unrecognized role for bile acids in drug conjugation. AB - Recently we demonstrated clinically significant levels of a previously unrecognized metabolite of the anticancer drug 5-fluorouracil (FUra) in bile of cancer patients. In the present study, reanalysis of bile from these patients demonstrated the presence of not one but two previously unrecognized metabolites. The major unrecognized metabolite was purified by reversed-phase HPLC, after which its molecular weight was determined by fast-atom-bombardment mass spectrometry to be 497. The similarity in HPLC retention times and molecular weights of this FUra derivative and the bile acids N-cholylglycine (Mr 465) and N cholyltaurine (Mr 515), along with the structural similarity of the FUra catabolite 2-fluoro-beta-alanine and the amino acids glycine and taurine, led to the hypothesis that this metabolite could be a conjugate of 2-fluoro-beta-alanine and cholic acid. This hypothesis was tested and confirmed by hydrolyzing the purified metabolite by cholylglycine hydrolase after which: 2-fluoro-beta-alanine was demonstrated by using a sensitive HPLC technique capable of resolving all of the known putative FUra metabolites, and unconjugated cholic acid was identified by both GC and GC-MS. Additionally, chemically synthesized N-cholyl-2-fluoro-beta alanine was shown to cochromatograph on HPLC and TLC with the purified biliary metabolite. In summary, this study demonstrates a unique, so far as we know, pathway of drug metabolism in man in which an amino acid drug metabolite is conjugated with cholic acid and eliminated into the bile. Furthermore, the finding that 2-fluoro-beta-alanine is conjugated to bile acids may provide some insight into the mechanism of cholestasis that is frequently observed after administration of fluoropyrimidine by hepatic arterial infusion. PMID- 3110787 TI - T-cell-replacing factor (interleukin 5) induces expression of interleukin 2 receptors on murine splenic B cells. AB - Small, resting B lymphocytes express few, if any, interleukin 2 (IL-2) receptors, but activated B cells may express such receptors. This paper examines the requirements for receptor expression. Normal murine splenocyte populations were enriched for B cells and cultured at relatively low density. IL-2 receptor expression was studied by measuring the binding of the anti-IL-2 receptor monoclonal antibody PC61. Lymphoblasts arising through stimulation by Escherichia coli lipopolysaccharide failed to express IL-2 receptors. B cells cultured with conditioned medium from concanavalin A-stimulated EL4 thymoma cells, with or without LPS, displayed IL-2 receptors. This bioactivity of EL4 conditioned medium could not be replaced by any concentration of B-cell-stimulatory factor 1 (IL-4), IL-1, IL-2, or IL-3 tested. However, the recently cloned lymphokine T-cell replacing factor (IL-5) was a potent inducer of IL-2 receptor expression, as was the probably identical material known as eosinophil differentiation factor. The receptors so induced appeared to be functional, as receptor-expressing (but not control) lymphoblasts, responded to IL-2 by proliferation, indicative of high affinity-receptor expression. PMID- 3110789 TI - Problems presented by animal toxicity studies. PMID- 3110790 TI - Purification of avian T cell growth factor and immune interferon using gel filtration high resolution chromatography. AB - A protocol was outlined to separate and purify chicken T cell growth factor or IL 2 and gamma interferon from conditioned medium of Con A activated spleen cells. IL-2 was associated primarily with a protein of 30 kDa in SDS-PAGE and in high resolution gel filtration chromatography. Chicken IL-2 was of low hydrophobicity. A second species of molecular weight 14 kDa was also identified by high resolution gel filtration chromatography. Purified IL-2 gave only 50% of the maximum growth response obtained with IL-2 in crude conditioned medium. Gamma interferon activity was associated primarily with protein of 17 kDa and a second peak of activity was detected with protein of 36 kDa. I-IFN was not cross reactive with human cells and was pH sensitive. PMID- 3110791 TI - A few germline genes encode the variable regions of chicken immunoglobulin light and gamma-heavy chains. PMID- 3110792 TI - Immunological traits of chicks selected for early and late immune response to E. coli and Newcastle disease virus. PMID- 3110793 TI - Characterization of two monoclonal antibodies against chicken T lymphocyte surface antigens. PMID- 3110794 TI - Affective disorders in general practice. Treatment of 6000 patients with fluvoxamine. AB - A total of 6258 patients seen in general practice complaining of low mood with or without associated somatic symptoms was studied. The mean patient entry score on the Montgomery-Asberg Depression Rating Scale (MADRS) was 29.69 (moderately severe depressive disorder). Three-quarters (73%) of the patients were female, average age was 46.1 years, and a reactive element was considered to be present in 43%. Patients received fluvoxamine, a novel anti-depressant, over a treatment period of 6 weeks, dosage starting at either 50 or 100 mg at night increasing after the first week, if necessary, to a maximum of 300 mg per day. Results were analyzed for 5625 patients. Efficacy of treatment was assessed using the MADRS, Psychosomatic Symptom Scale and Clinical Global Impression scales. During treatment, there was a marked improvement in mood and a parallel improvement in somatic symptoms; there was no difference in overall response between those with or without somatic symptoms. By Week 6, patients had improved by approximately 65%, with suicidal ideation being most marked at 81%. Patient compliance was good, the most commonly reported unwanted effect being nausea. In overdoses up to 2 g fluvoxamine no lasting toxic effects were observed. In an 'elderly' sub-group of 1096 patients aged 60 years and over, efficacy and the incidence of unwanted effects were similar, but the drop-out rate due to intolerance was greater than in the younger age sub-group. PMID- 3110795 TI - Nucleus accumbens opiate-dopamine interactions and locomotor activation in the rat: evidence for a pre-synaptic locus. AB - Locomotor activation produced by the indirect dopamine (DA) agonist amphetamine is reversed by the opiate-receptor antagonist naloxone. Since amphetamine stimulated locomotion results from the release of DA within the nucleus accumbens (N.Acc.), it is possible that these effects of naloxone result either from a decrease in the pre-synaptic release of DA within the N.Acc. or from a disruption of the effects of DA at, or distal to, the post-synaptic DA receptor. In the present study, we investigated the effects of naloxone on the locomotor activating properties of dopamine injected directly into the nucleus accumbens. Naloxone (0-2 mg/kg) had no significant effect of DA-stimulated locomotion; the lowest dose of naloxone tested (0.5 mg/kg) was shown to significantly disrupt the locomotor activation produced by amphetamine (0.5 mg/kg). In separate animals, very high doses of naloxone (5.0 mg/kg) had no significant effect on locomotor activation produced by the DA receptor agonist apomorphine in rats following 6 hydroxydopamine (6OHDA) denervation of the N.Acc. These results indicate that naloxone must disrupt amphetamine-stimulated locomotion through its action presynaptic to N.Acc. DA receptors. PMID- 3110796 TI - Altered splenic catecholamine concentrations during experimental allergic encephalomyelitis. AB - Catecholamine concentrations of the spleen were studied with neurochemical techniques in rats injected with myelin basic protein to produce an experimental allergic encephalomyelitis (EAE). Thirteen to 14 days postinoculation the affected rats showed peak clinical signs of weakness, especially in the lower extremities. Resolution of the disease then progressed rapidly with full clinical recovery at day 21. Splenic concentrations of norepinephrine (NE), 3,4 dihydroxyphenylalanine (DOPA), epinephrine (EPI) and 3,4 dihyxroxyphenylethylamine (DA) were determined by HPLC with electrochemical detection. DOPA concentrations were significantly increased (+62%) while DA concentrations were decreased (-29%) in the EAE rats on day 14 postinoculation. NE and EPI concentrations tended to be elevated in the EAE group, but this was not statistically significant. No differences in splenic catecholamines were detected on day 7 and 52 postinoculation between EAE and control animals. These results indicate that changes in the metabolic pathways of splenic catecholamines occur at the peak of the clinical symptoms of EAE; the increase in DOPA and the decrease in DA concentrations suggest that the activity of DOPA-decarboxylase or its co-factor is altered. PMID- 3110797 TI - [Germ reduction by microwaves--microwave specific effects]. AB - A commercial 2450-MHz microwave oven has been used to inactivate microorganisms in pharmaceutical solutions and auxiliary materials. The present investigation is concerned with the possible existence of a specific microwave effect, potentiating the thermal effect of microwave irradiation. Bacillus subtilis suspensions in polyethylenglycol 300, distilled water and peanut oil were used. It is shown that microwave heating is significantly more lethal to Bacillus subtilis microorganisms than equivalent conventional heating. PMID- 3110798 TI - Effects of treatment with DNA-directed cancer chemotherapeutic agents after polyamine depletion. PMID- 3110799 TI - Pituitary sensitivity to thyroid hormones in depressed patients. AB - To evaluate the feedback control of thyroid hormones on TSH release, 18 normal subjects and 16 depressed patients received two TRH injections: on days one and nine. Forty eight hours before the second TRH injection subjects and patients received either T3, 100 micrograms orally, or matched placebo. T3 administration resulted in a highly significant and similar reduction of delta max TSH and FT4 index levels in both subjects and patients whereas serum T3 levels were unchanged. These data suggest that the pituitary response to the negative feedback signal of T3 is intact in depressed patients. PMID- 3110800 TI - Evaluation of the diagnostic utility of the TRH-induced TSH response in psychiatric disorders. AB - To evaluate the diagnostic utility of TSH blunting, the TRH-induced TSH response was measured in 168 normal subjects and 176 psychiatric patients. It was blunted in some acutely depressed, alcoholic, and borderline patients, but not in schizophrenic patients. In both depression and alcoholism the fault also occurred during symptomatic recovery, though with reduced frequency. Although TSH blunting was useful in distinguishing between borderline and schizophrenic patients, its diagnostic utility in identifying or confirming an existing psychiatric disorder appears to be limited. TSH blunting is not specific for any particular psychiatric diagnosis, and its sensitivity generally is low. However, the fault has promising research utility, particularly for study of the biologic interface between depression, alcoholism and borderline personality disorder. Beyond this, further study of the possible trait nature of TSH blunting in both depression and alcoholism appears warranted. PMID- 3110801 TI - Plasma prolactin response to submaximal stimulation by TRH and endogenous corticosteroids in man. AB - Recent studies suggest that submaximal plasma prolactin responses to TRH may reflect the effects of endogenous dopamine on prolactin release more accurately than basal plasma prolactin levels or maximal plasma prolactin responses to TRH. In the present study the plasma prolactin response to 12.5 micrograms i.v. TRH in 25 male subjects was significantly correlated with 24-hour urinary 17-ketogenic steroid excretion (= "total" 17-hydroxy corticosteroids). With regard to the basal plasma prolactin level or the prolactin response to 200 micrograms i.v. TRH, no such relation with corticosteroid excretion was detected. It is concluded that the plasma prolactin response to 12.5 micrograms i.v. TRH may provide a new, useful investigative tool with which to study corticosteroid-dopamine interactions and central dopamine activity in man. PMID- 3110802 TI - An improved HPLC method for the separation of retinaldehyde isomers from visual pigments. PMID- 3110803 TI - Risk factors in ulcer disease. A case-control computer processed study. AB - Risk factors in patients with ulcer disease have been investigated on a random sample of 214 in-patients admitted during 1985 to two clinical departments. For data collecting, an original questionnaire was developed and submitted. Results were obtained by computer processing. The method permitted quantification of the prevalence of risk factors in peptic ulcer in Romania and also of the relations between them. PMID- 3110804 TI - Studies concerning chronic and acute effects of L-carnitine on some biological parameters in elite athletes. AB - Chronic and acute effects of L-carnitine have been recorded in a group of elite athletes by a prospective double blind placebo controlled trial. Forty top athletes (20 boys, kayak-canoe, 10 weightlifters and 10 girls, rowers) received orall 3 g L-carnitine daily for 3 weeks while 38 top athletes (20 kayak-canoe, 8 weightlifters and 10 rowers) received the same medicine as placebo. Significant changes were registered in the treated group concerning FFA and triglycerides, strength index, VO2max., urinary mucoproteins and in the control group concerning Ld (distal latency). All athletes were under medical supervision and had a controlled training program and food. The effects of a single oral dose (4 g L carnitine were recorded in a group of 18 top weightlifters under basal conditions and 90' after L-carnitine ingestion. Significant changes in the treated group were registered for the FFA, triglycerides, urinary mucoproteins and distal latency of the right and left median nerve. Based on these data the authors recommend this aminoacid both for chronic and acute effects as a physiological mean for the biological preparation of elite athletes during hard training and competitions. PMID- 3110805 TI - Aspects of the hepatic rheogram within the medical practice. AB - In many cases, the diagnosis of different hepatic affections can be established or confirmed through the usage of some approaches to the hepatic circulation, approaches that can point out the intrahepatic morphopathological processes that in fact explain the functional state as well. Starting from these considerations, this paper investigates the hemodynamic modifications and the hepatic irrigation using a non-invasive method--rheography. PMID- 3110806 TI - [Hydrochloric acid secretion and its correlation with the pathological electromyogram]. PMID- 3110807 TI - Fibronectin and phagocytosis in acute and chronic infections. AB - Serum fibronectin (Fn) level and phagocytosis function were investigated during acute and chronic infections. Serum Fn concentration was significantly decreased in septic patients (mean +/- ES, 80 +/- 12 micrograms/ml, p less than 0.001) and was increased in chronic bronchitis patients (575 +/- 18 micrograms/ml, p less than 0.001) as compared to the controls. The phagocytosis index was decreased in septicaemia and not significantly changed in chronic bronchitis. Phagocytosis dysfunction was associated to a low serum Fn level in acute infections. Phagocytosis was stimulated in vitro, by purified Fn. Serum Fn concentration reflects the reticuloendothelial function and could be a marker of infection together with other parameters. PMID- 3110808 TI - Investigation regarding the VIth cardiac sound under pathological and normal physiological condition. AB - Starting from the fact that specialty data regarding a VIth cardiac sound, are scarce the paper studies the phonocardiogram recorded on four frequency bands in parallel with a EKG derivation and a carotid pulse in a lot of 532 persons (healthy and sick) using a 6-NEK-4-apparatus. The presence of this sound has not been remarked in healthy persons. In 5% out of the tested sick that presented aortic insufficiency we remarked the presence of a VIth cardiac sound of a low frequency and amplitude, possibly of a vascular nature. In all the patients that exhibited this VIth sound a 50% increase of the left ventricle ejection period as well as a 26% increase of the preejection period was noticed. The presence of this sound in the aged patients with stenosis and aortic insufficiency, exhibiting reductions of the vascular wall elasticity was not remarked. PMID- 3110809 TI - Sinus node dysfunction occurring immediately after pericardiocentesis. AB - Performing in two cases three instances of pericardiocentesis, there always occurred sinus node dysfunction. Our explanation is of a mechanical involvement of the sinus node after the complete evacuation of the pericardial fluid. PMID- 3110810 TI - Inhibition of aldose reductase activities by kampo medicines. PMID- 3110811 TI - Effects of caffeoylglycosides on arachidonate metabolism in leukocytes. PMID- 3110812 TI - Nutritional support of cancer patients. AB - The maintenance of nutritional status in cancer patients is a critical part of the overall care. The cachetic, malnourished patient represents a compromised host that may be less responsive to aggressive antitumor therapy. Assessment and monitoring of nutritional status should begin as soon as the diagnosis is made, as maintenance of good nutritional standing is far easier and less expensive than rehabilitating a depleted patient. PMID- 3110813 TI - [Patients with brain damage in childhood as adults. Results of a follow-up study]. PMID- 3110814 TI - [Effect of carbamazepine on the velocity of saccades]. AB - In 5 female patients suffering from focal epilepsies, the maximal velocity of saccades was determined before and during carbamazepinE therapy. A decrease in the velocity of saccades was followed by an increase at the same serum level. PMID- 3110815 TI - [Clinical trial of contemnol tablets (lithium retard Spofa)]. AB - A report on the clinical testing of the lithium-retard medicament Contemnol (Spofa). It details the way lithium-retard treatment is objectively and subjectively superior to the earlier and still current general lithium treatment. PMID- 3110816 TI - Concurrent lithium administration results in higher haloperidol levels in brain and plasma of guinea pigs. AB - The effects of lithium (Li) on brain and plasma levels of concurrently administered haloperidol (HAL) were investigated. One group of guinea pigs (n = 12) was also treated with HAL for 11 days, but Li was added during the last 5 days of treatment. At the end of treatment, the HAL + Li group had significantly higher brain and plasma levels of HAL than the group treated with HAL alone. The correlation coefficient between plasma and brain HAL (0.97) indicated that plasma levels of HAL determine brain levels of this drug. PMID- 3110817 TI - The role of attention in the preparation of visually guided eye movements in monkey and man. PMID- 3110818 TI - Peripheral, autonomic regulation of locus coeruleus noradrenergic neurons in brain: putative implications for psychiatry and psychopharmacology. AB - In 1946 von Euler identified the major transmitter of sympathetic nerve fibers, norepinephrine (NE), and about a decade later Vogt (1954) provided the first evidence that NE may also serve as a neurotransmitter in the central nervous system (CNS). Since that time, a literal explosion in CNS neurotransmitter research has taken place involving histological, biochemical, physiological, pharmacological and clinical investigations. Yet, it is only now that we are beginning to understand the biological function of NE in brain, in particular because of recent advances regarding the physiology and regulation of NE neurons in locus coeruleus (LC), a bilateral pontine structure with a uniquely wide spread terminal network reaching throughout the neuroaxis and in primates accounting for about 70% of all brain NE. Recently, the neurobiology of the LC noradrenergic network was extensively reviewed by Foote et al. (1983), and its implication in vigilance as well as global orientation of behavior towards imperative, environmental sensory stimuli was outlined. Yet, more recent information regarding the peripheral, autonomic regulation of LC neurons in brain provides fundamentally new biological aspects on behavior and mental function which seem to allow a more integrated view of the role of brain NE in the overall function of the individual than previously understood. The purpose of this review is to summarize these findings and, furthermore, to outline some putative implications for psychiatry and neuropsychopharmacology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110819 TI - Diazepam, behavior, and aging: increased sensitivity or lower baseline performance? AB - Cognitive performance, psychomotor skills, and subjective reactions to diazepam and placebo were compared in 12 healthy, well-educated subjects in three age groups: 19-28, 40-45, and 61-73 years old. With only minor exceptions, the changes in performance caused by diazepam and age differences were statistically additive and noninteracting. Diazepam did not act synergistically in older individuals; the decrements in performance were about the same in all age groups. Baseline performance decreased with increasing age; middle-aged subjects performed more like older than younger subjects. A variety of tasks exhibited similar effects of aging and diazepam, i.e., when performance declined with increasing age, it was also reduced by diazepam. PMID- 3110821 TI - Subjective effects of cigarette smoking in adolescents. AB - Eighty-two per cent of a sample of 170 female adolescent smokers reported experiencing one or more of five specified subjective effects of smoking. Feeling calmer was the most frequently reported effect and daily smokers were more likely to report this than non-daily smokers (64% versus 38%, P less than 0.001). Self reports of cigarette consumption and depth of inhalation and measures of smoke intake (salivary cotinine and expired-air carbon monoxide levels) were positively related to the report of feeling calmer when smoking and negatively related to feeling dizzy/light-headed and sick when smoking. The likelihood of experiencing at least one withdrawal effect when trying to quit was greater amongst those who reported feeling calmer when smoking (82% versus 40%, P less than 0.001). These results indicate that subjective effects of smoking are commonly reported by children and it is possible that pharmacological factors are implicated alongside psychosocial ones even at this early stage. PMID- 3110820 TI - Effects of brofaremine (CGP 11 305A), a short-acting, reversible, and selective inhibitor of MAO-A on sleep, nocturnal penile tumescence and nocturnal hormonal secretion in three healthy volunteers. AB - The effects of brofaremine (CGP 11 305A), a short-acting, reversible and selective inhibitor of MAO-A, on sleep, nocturnal penile tumescence (NPT) and hormonal secretion during the night were studied during a long-term trial. Three healthy males underwent sleep-EEG and NPT recordings during consecutive nights (1) under placebo, (2) under stepwise increasing dosages of brofaremine and (3) under placebo after withdrawal. Hormone profiles were sampled during selected nights to analyze the plasma concentration of cortisol, HGH, prolactin, testosterone, LH and FSH. REM sleep was suppressed markedly under 150 mg brofaremine, while stages 1 and 2 increased. In comparison to the effect of irreversible MAOIs the REM suppression was shorter and did not persist after withdrawal. A decrease of the plasma concentration of the drug coincided with a return of sleep variables to baseline values. A REM rebound occurred after withdrawal of brofaremine. REM sleep and NPT showed a dissociation; NPT variables did not follow the decrease of REM sleep. The effects of REM parameters are correlated with the dosage and the plasma concentration of the substance. Intraindividually, a decrease in secretion of HGH was observed throughout the trial. No marked changes were found in the other endocrinological variables. PMID- 3110822 TI - Cardiovascular and subjective effects of smoking before and after 24 h of abstinence from cigarettes. AB - Cigarette-induced changes in heart rate, skin temperature and subjective state were measured during the course of a normal smoking day and on smoking after 24 h abstinence in 21 smokers. Heart rate was not affected by smoking a test cigarette during the normal day's smoking, but after 24 h abstinence smoking a cigarette caused an average increase of 14 beats per min. Skin temperature, on the other hand, was reduced by smoking a cigarette under both conditions. Subjective effects of smoking were experienced only after the period of abstinence. The most common was dizziness, but nausea and other effects were also reported. Cigarette induced changes in heart rate and skin temperature were positively correlated with each other, and the rise in heart rate after abstinence correlated positively with the strength of the subjective response. The results are discussed in terms of similarities and differences between different physiological systems in tolerance to the effects of nicotine. PMID- 3110823 TI - Strain differences in response to drugs in the tail suspension test for antidepressant activity. AB - The effects of several types of antidepressants in a recently developed "behavioural despair" model, the tail-suspension test, are described. Drug effects on the automatically recorded duration of immobility and power of movements were measured in three strains of mice. Only in one strain (NMRI) did almost all antidepressants tested showed the expected reduction in duration of immobility. Tranquillizing drugs, but not stimulants, could be distinguished from antidepressants. The power of movements could not definitively be related to the pharmacological profile of the drugs tested. The use of the tail-suspension test as a rapid and highly predictive behavioural primary screen for antidepressant drugs is suggested. PMID- 3110824 TI - Serotonin function in anxiety. II. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects. AB - To assess the role of serotonin function in the development of panic anxiety, the behavioral and biochemical responses to the serotonin receptor agonist, m chlorophenylpiperazine (MCPP) was examined in healthy subjects and agoraphobic and panic disorder patients. MCPP had anxiogenic effects in both the healthy subjects and patients. Panic attacks meeting DSM-III criteria occurred following MCPP in 12 of 23 patients and 6 of 19 healthy subjects (NS) and other ratings of anxiety also did not distinguish the two groups. MCPP resulted in significant but similar increases in cortisol, prolactin, and growth hormone in the healthy subjects and patients. The results of this investigation suggest that serotonin neuronal dysfunction may not be of etiologic significance in most panic disorder patients. However, the observed anxiogenic properties of MCPP suggest that additional studies of the role of serotonin systems in the pathophysiology of human anxiety disorders are indicated. PMID- 3110825 TI - Chronic nicotine and locomotor activity: influences of exposure dose and test dose. AB - Repeated exposure to nicotine increases both the number of central nicotinic receptors and the behavioral stimulant effect of nicotine. In the present experiments, the behavioral response to nicotine was examined in photocell activity cages. Groups of rats were tested using doses from 0.1 to 1.6 mg/kg both before and after all rats were exposed for 5 days to a common dose of 0.2 mg/kg/day. Prior to the 5-day exposure, there was a dose-related stimulant response to nicotine, with a maximum response seen at 0.4 mg/kg. After the 5-day exposure, the dose-effect curve was shifted upward, so that greater stimulation was produced at each test dose of nicotine. Other groups of rats were exposed for 5 days to doses of nicotine ranging from 0.01 to 0.30 mg/kg/day. On the 6th day all rats received a common test dose of 0.2 mg/kg and their response was measured in the activity cages. In animals exposed to 0.01 mg/kg/day, the test day response was not different from saline controls, but the groups exposed to higher doses showed increased stimulation in response to the common test dose. Measurements of nicotinic receptor binding using [3H]-acetylcholine found increased binding in groups receiving 0.03 mg/kg/day or more, but not in the group that received 0.01 mg/kg/day. The correspondence between the doses that increase behavioral stimulant reactions to nicotine and the doses that increase nicotinic binding suggest that increased receptor numbers may be responsible for the increased behavioral stimulation. However, rats given high doses (1.6 mg/kg, twice per day) did not show increased behavioral stimulation to a test dose of 0.2 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110826 TI - Long-term effects of yohimbine on behavioral sensitivity to a stressor. AB - Two experiments examined the long-term effects of repeated administration of yohimbine, a suspected anxiogenic drug, on behavioral sensitivity to a conditioned cue for shock. In Experiment 1, rats were trained to bar press following injection of yohimbine (either 1 or 2 mg/kg) or saline. At the end of this training, injections were suspended and the rats were given Pavlovian fear conditioning to establish a light as a shock signal. Rats were then returned to the bar press situation (about 2 weeks after their last injection) and the capacity of the light to disrupt responding was tested. Rats previously treated with yohimbine were less disrupted by the light than were controls. In contrast, Experiment 2 found that previously experiencing the yohimbine-induced state only in the home cage increased subsequent disruption of bar pressing by the light. Yohimbine pretreatment had no effect on acquisition of freezing behavior to the light, nor on bar pressing during testing in the absence of the light, in either experiment. The results show that yohimbine can have long-term effects on behavior in the presence of a stressor, and that the nature of these effects are dependent upon environmental and/or behavioral context in which the yohimbine induced state was experienced. These findings appear compatible with an internal stimulus view of stress and stress inoculation. PMID- 3110827 TI - A behavioural and neurochemical analysis of chronic and selective monoamine oxidase inhibition. AB - The effects of clorgyline were compared with the effects of (-)-deprenyl using measures of rewarding hypothalamic self-stimulation, regional monoamine metabolism and monoamine oxidase activity. Male Wistar rats trained to self stimulate at half-maximal rates with unilateral bipolar lateral hypothalamic electrodes on a continuous reinforcement schedule were implanted subcutaneously with osmotic minipumps which delivered 1 mg X kg-1 drug per day or vehicle for 13 days. A response rate/stimulation frequency (reward summation) function was determined the day before minipump implantation and on days 5 and 13 of drug administration. Only clorgyline induced a shift to the left in the reward summation function at 5 and 13 days, indicating enhancement of reinforcement. Clonidine (50 micrograms X kg-1 IP) probe tests were run on days 2 and 10 to determine the sensitivity of alpha 2-noradrenaline receptors. Clorgyline induced an attenuation of the clonidine response on day 10 relative to day 2. The other groups exhibited no change in response to clonidine. Clorgyline also induced a progressive increase in self-stimulation rates; this effect was not observed with the other groups. The clorgyline effects were accompanied by an increase in regional brain levels of dopamine, noradrenaline and 5-hydroxytryptamine and a reduction of their acid metabolites. Clorgyline selectively inhibited type A monoamine oxidase, whereas (-)-deprenyl selectively inhibited type B monoamine oxidase. PMID- 3110828 TI - Isolation housing decreases the effectiveness of morphine in the conditioned taste aversion paradigm. AB - Male Long Evans rats were obtained at 21 days of age and were housed in either an aggregated (four per double cage) or isolated (one per single cage) condition for 6 weeks. They were then placed on a fluid deprivation schedule that allowed them access to fluids for 20 min daily. This schedule was maintained for the remainder of the experiment. Following habituation, sensitivity to morphine-induced conditioned taste aversion (CTA) was compared in the differentially housed rats. On the 1st day and every 5 days thereafter the rats were presented with a 0.1% solution of sodium saccharin for the 20-min drinking period, followed immediately by an injection of morphine (0, 2.5, 5.0, 10.0, or 20.0 mg/kg). On intervening days they received water as the fluid. No drugs were given on these days. There was no difference in baseline saccharin consumption as a function of housing condition. In comparison with the isolated rats, the grouped animals were more sensitive to the CTA-inducing properties of low doses of morphine. These data strengthen the already existing evidence for the influence of the early housing environment on drug sensitivity and provide additional support for the conclusion that variability in response to a number of drugs of abuse can be reduced by environmental means. Possible mechanisms for the differences between isolation and aggregation housed rats are discussed. PMID- 3110829 TI - Classical conditioning of amphetamine-induced lateralized and nonlateralized activity in rats. AB - Amphetamine-induced lateralized activity (rotation) and nonlateralized activity (extra quarter turns) was classically conditioned in female rats using the test environment as the conditioned stimulus (CS) and 1.25 mg/kg d-amphetamine as the unconditioned stimulus. Conditioned lateralized activity extinguished more rapidly than nonlateralized activity. Also, d-amphetamine-induced nonlateralized activity was selectively decreased by a schedule of 50% partial reinforcement. These results indicate that the two d-amphetamine responses can be distinguished, that they are differentially affected by learning, and that a schedule of partial reinforcement can selectively attenuate one effect of a drug while leaving the other intact. In addition, haloperidol blocked conditioned lateralized activity; this suggests that the conditioned response may be, like the drug-induced response, mediated by dopamine. PMID- 3110830 TI - Effect of combined or separate administration of piracetam and choline on learning and memory in the rat. AB - Different groups of rats received combined or separate administration of different doses of piracetam (P1:100, P2:200, and P4:400 mg/kg) and choline (C1:100 and C2:200 mg/kg). Compared to control treatment, C1 significantly improved performance in a delayed alternation (DA) task, while P1, P2, P4 or P1C1 had no effect. Moreover, rats receiving P2C1 and P4C1 were significantly inferior in acquiring DA to rats receiving the vehicle or separate administration of P1, P2 or C1. The different treatments with combined or separate administration of P and C had no effect on spontaneous locomotor activity and two-way avoidance conditioning. In a recognition-task only groups C1 and P4 were able to discriminate between familiar and new objects. The combined or separate administration of P1 and C1 on NA, DA, DOPAC, 5-HT, 5-HIAA levels, CAT activity and choline uptake were measured in frontal cortex and hippocampus: the only significant effect was a 5-HT increase in the hippocampus of rats treated with C1. PMID- 3110831 TI - The relationship between hindlimb disturbances, forelimb disturbances and catalepsy after increasing doses of muscimol injected into the striatal-pallidal complex. AB - To establish the role of the GABA-ergic mechanism within the striatal-pallidal complex in hindlimb disturbances, forelimb disturbances and catalepsy and the relationship between these phenomena, the effects of the locally injected GABA agonist muscimol (0.5 microliter per side) were investigated in rats using several specific tests of catalepsy. The time required for retracting free hanging hindlimbs was dose-dependently prolonged by 2-10 ng muscimol. The time required for releasing a rod that was clasped between the forelegs of otherwise free-hanging rats was dose-dependently prolonged by 5-10 ng muscimol. Likewise, the time required for retracting the free-hanging forelimbs was dose-dependently prolonged over the same dose range. Finally, the time during which standing rats kept their forelimbs on a block of 9 cm height (the dependent variable used in "classic" tests of catalepsy) was only prolonged at the highest dose (10 ng) of muscimol. The effects of the latter dose, which lasted at least 30 min, were inhibited by the GABA antagonist bicuculline (50 ng) for a minimum period of 5 min. The present data show that the GABA-ergic mechanisms within the striatal pallidal complex are involved in hindlimb disturbances, forelimb disturbances and catalepsy, and that catalepsy requires a stronger dysfunctioning of these GABA ergic mechanisms than do disturbances in hindlimbs and forelimbs. PMID- 3110832 TI - The effects of repeated doses of ethanol on exploration and its habituation. AB - The effects of ethanol (0.8-2.4 g/kg) on exploratory behavior and its habituation were investigated by testing DBA/2 mice in a holeboard apparatus. Mice familiar with the holeboard had lower levels of exploration than animals with no previous experience in the apparatus. If the animals received ethanol during their first exposure to the holeboard they did not show the same degree of habituation. Ethanol (0.8 g/kg) increased the exploration of animals naive to the holeboard, but failed significantly to increase the exploration of animals familiar with the apparatus. An increase in locomotor activity was observed following treatment with ethanol (2.4 g/kg). This was potentiated if animals received a single treatment with ethanol 3 days earlier, but only if they were tested in the apparatus following the initial treatment. These results have important implications for the design of experiments investigating tolerance and sensitization to ethanol's effects on locomotor activity and exploration. PMID- 3110833 TI - Apparent absence of nicotine-induced conditioned place preference in rats. AB - The conditioned place preference (CPP) paradigm was used in order to assess the reinforcing actions of nicotine in rats. Subjects were tested in "unbiased" two compartment shuttle boxes, so-called because neither compartment was consistently preferred prior to drug conditioning. In the first experiment, subjects that were initially drug naive showed neither a preference nor an aversion to the compartment that had been paired on four occasions with injection of nicotine (0.2-0.8 mg/kg SC); a similar result occurred in another group given daily injections of nicotine in the home cage prior to the experiment. In a second experiment, nicotine (0.4, 0.8 mg/kg SC) again failed to produce a CPP, whereas marked CPPs were seen in parallel groups of rats tested with either d-amphetamine or methylphenidate. Although nicotine has been reported to produce conditioned place preference, the present results suggest that it is not a robust phenomenon. PMID- 3110834 TI - Ontogeny of GABA-ergic and dopaminergic mediation of gnawing behavior in the mouse. AB - The ontogenetic course of dopaminergically mediated gnawing and the potentiation of this behavior by muscimol (a GABA receptor agonist) was explored in developing and young adult mice using a time-sampling (in 5-, 8-, 11-, and 14-day-old pups), or a corrugated paper procedure (in 14-, 17-, 20-, 23-, 26-, 35-, and 53-day-old animals). In experiment 1, the older mice group (14-53 days), displayed a dose dependent gnawing behavior after methylphenidate, a dopamine indirect agonist (20, 30, 50 mg/kg). Similarly, in 5-, 8-, 11-, and 14-day-old pups, methylphenidate (10, 20, 50 mg/kg) evoked stereotyped gnawing (or indissociable gnawing-licking in 5-day-old pups), with maximal effects after the two lower doses at 8-11 days of age (experiment 2). Muscimol pretreatment (dosages ranging from 0.025 to 1.3 mg/kg) induced a clear-cut potentiation of gnawing elicited by methylphenidate (10 or 20 mg/kg) as early as 8 days of age (experiments 3 and 4). However, muscimol did not potentiate gnawing in 5-day-old pups treated with 10 or 2.5 mg/kg methylphenidate. The effectiveness of methylphenidate in inducing gnawing-licking among 5-day-old pups confirms the early maturation of central dopamine receptors reported in the literature. It is speculated that the absence of potentiating action of muscimol on methylphenidate-induced gnawing-licking at this age may be due to a functional immaturity of the GABAergic striato-nigro tectal system, which is thought to transmit dopaminergic striatal stereotyped response at the output stations (recent review by Scheel-Kruger 1986).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110835 TI - Nicotine and smoking: a perspective from animal studies. AB - Nicotine plays a key role in reinforcing tobacco smoking, and exerts several psychoneuropharmacological actions which may contribute to its reinforcing effects. Thus, nicotine can improve mood and alleviate withdrawal symptoms; it can also alter CNS arousal, reduce stress, suppress appetite, and improve performance on certain tasks. Behavioural studies in animals have tended to corroborate existing theories of smoking behaviour, and have started to suggest how and where nicotine may exert its central actions in man. Clinical evidence suggests that smoking cessation would be facilitated by the administration of a nicotinic antagonist having a selective action on central nicotinic cholinoceptors of the C6 (ganglionic) type. Pharmacological studies in animals indicate that such a drug is a reasonable prospect. PMID- 3110836 TI - The role of the aural head shake reflex in serotonin-mediated head shaking behavior. AB - The head shake reflex is a rapid rhythmic shaking of the head in a radial motion and is a prominent part of the behavior of most mammalian species. The administration of agonists at 5-hydroxytryptamine (5-HT) receptors to rats increases apparently-spontaneous head shaking behavior. The present study examined the relationship between the head shake reflex, elicited by stimulation of the aural ampullae with Tween 80, with a similar-appearing behavior, the head shake response caused by the administration of 5-HT agonists to rats. Head shaking was attenuated by the subcutaneous infiltration of the local anesthetic procaine into the posterior border of the external auditory meatus. However, the local anesthetic did not alter head shake behavior produced by administering either the 5-HT agonist quipazine or the 5-HT precursor 5-hydroxy-L-tryptophan (L 5-HTP). The magnitude of the head shake reflex was also diminished after habituation of the reflex by repeatedly applying Tween 80 to the ampullae, yet this treatment had no effect on the head shaking behavior caused by quipazine. In a complementary manner, pretreatment with the 5-HT2 receptor antagonist ketanserin potently blocked shaking behavior caused by quipazine without significantly altering the head shake reflex. Chronic administration of the atypical antidepressant drug iprindole to rats for 7 days reduced quipazine induced shaking behavior without affecting the head shake reflex. In contrast, chronic administration of the monoamine oxidase inhibitor phenelzine to rats for 7 days reduced head shaking behavior caused by either stimulus, indicating that an attenuation of motor reflex activity could play a role in the reduced response to quipazine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110837 TI - Assessment of grooming and other behavioural responses to the D-1 dopamine receptor agonist SK & F 38393 and its R- and S-enantiomers in the intact adult rat. AB - The behavioural effects of the D-1 dopamine receptor agonist SK & F 38393 were assessed in the intact adult rat using a conventional stereotypy rating scale and a rapid time sampling behavioural check list procedure. This combination technique allowed description of the nature of any behavioural response and quantification of the number of counts of individual behaviours. Using this combined procedure, SK & F 38393 clearly failed to induce typical stereotyped behaviour. However, in the well-habituated animal, SK & F 38393 dose-dependently increased the number of recordings of non-stereotyped sniffing, locomotion and grooming; some occasional rearing was also noted. An unusual pattern of intense grooming behaviour was a characteristic response to this drug. Using the resolved R- and S-enantiomers of SK & F 38393, promotion of sniffing, locomotion, rearing and grooming resided stereoselectively in the R-configuration. Under appropriate experimental conditions, specifically a requirement for prolonged habituation and the use of a rapid sampling behavioural check list to supplement the rating scale, it is possible to demonstrate that SK & F 38393 is behaviourally active in the whole animal. PMID- 3110838 TI - Behavioral teratogenicity of valproic acid: selective effects on behavior after prenatal exposure to rats. AB - Pregnant Sprague-Dawley rats were treated with 0, 150 or 200 mg/kg valproic acid by gavage (VPA) on days 7-18 of gestation. These doses produced no maternal toxicity, reproductive effects or effects on offspring growth and survival. Maternal plasma VPA peak levels averaged 99 and 134 micrograms/ml 1 h after the last treatment, values approximating human therapeutic levels. VPA offspring tested after weaning exhibited reduced open-field central, but not peripheral, activity and reduced hole-board horizontal, but not vertical, activity. No activity differences were found in a figure-8 test or a preweaning activity test. The VPA offspring also showed lengthened straight channel swimming times, increased swimming maze errors, but only among the females, while producing no differences in maze times. VPA offspring exhibited reduced spontaneous alternation frequency and reduced startle responding to both auditory and tactile (air-puff) stimuli. The effects of VPA were dose dependent in some cases (straight channel swimming and water maze errors), or the effect was seen only in the high-dose group (open-field, hole-board, spontaneous alternation, startle). The conclusion was reached that prenatal VPA is behaviorally teratogenic in rats at relevant maternal blood concentrations and at non-malforming doses. PMID- 3110839 TI - The use of a plus-maze to measure anxiety in the mouse. AB - To investigate whether an elevated plus-maze consisting of two open and two closed arms could be used as a model of anxiety in the mouse, NIH Swiss mice were tested in the apparatus immediately after a holeboard test. Factor analysis of data from undrugged animals tested in the holeboard and plus-maze yielded three orthogonal factors interpreted as assessing anxiety, directed exploration and locomotion. Anxiolytic drugs (chlordiazepoxide, sodium pentobarbital and ethanol) increased the proportion of time spent on the open arms, and anxiogenic drugs (FG 7142, caffeine and picrotoxin) reduced this measure. Amphetamine and imipramine failed to alter the indices of anxiety. The anxiolytic effect of chlordiazepoxide was reduced in mice that had previously experienced the plus-maze in an undrugged state. Testing animals in the holeboard immediately before the plus-maze test significantly elevated both the percentage of time spent on the open arms and the total number of arm entries, but did not affect the behavioral response to chlordiazepoxide. The plus-maze appears to be a useful test with which to investigate both anxiolytic and anxiogenic agents. PMID- 3110840 TI - Effects of repeated alcohol administration on human operant behaviour. AB - Nine human subjects were exposed to a multiple fixed-ratio (FR) differential reinforcement-of-low-rate (DRL) schedule of monetary reinforcement. Presses on a manipulandum requiring relatively high force were occasionally followed by an increased money total displayed on a computer screen. Subjects were exposed to the schedule until their behaviour had stabilized. Prior to each of the next three sessions they were administered 0.85 g/kg alcohol. In eight of the nine subjects the initial effect of alcohol was to increase FR response rate and, consequently, reinforcement rate. Subsequent alcohol administration resulted in sensitization: even greater rate-increasing effects. In two further control sessions behaviour returned towards baseline level. DRL response rate was slightly increased by alcohol, but reinforcement rate remained unchanged. There was no consistent change in DRL response or reinforcement rates from the first to the third alcohol sessions. The effects of alcohol on human behaviour were similar to the effects found in studies with animals. The results were also consistent with the view that the changes in behaviour which occur with repeated drug administration depend in part on whether the initial effect of the drug is to increase, decrease or produce no change in reinforcement rate. PMID- 3110842 TI - Environmental stimulation promotes recovery from haloperidol-induced extinction of open field behavior in rats. AB - Rats receiving 0.1 mg/kg haloperidol showed a progressive decline in their rate of spontaneous motor activity in an open field environment, suggesting that incentive motivational properties of stimuli in the experimental situation may be blunted by neuroleptic treatment. After removal for a short time-out in the home cage they were re-tested in this, or a novel stimulus environment, for a second observation session. Under novel (but not familiar) stimulus conditions haloperidol-treated rats showed an enhancement of spontaneous activity, similar to that observed in vehicle-treated animals, and exceeded their previous low rates of crossing and rearing responses. As drug conditions were similar for the two haloperidol groups, it is likely that neuroleptic-induced effects on spontaneous motor behavior are sensitive to the stimulus complexity of the environmental situation. PMID- 3110841 TI - Alcoholic-like drinking in simian social groups. AB - We have developed two protocols for inducing sustained, high-dose, alcohol reinforced, oral alcohol drinking among some members of Macaca nemestrina social groups. Both protocols initially co-present alcohol and the entire daily food supply in a 2-h daily drinking session, with a later return to continuous availability of food. One protocol presents unflavored aqueous alcohol to partially food-deprived subjects; the other compares the drinking of flavored alcohol solutions with the drinking of equally palatable isocaloric non-alcohol solutions when monkeys are not deprived of food. Daily high-dose drinking developed in both protocols, with biomedical changes similar to those of early human alcoholism. Daily drinking to blood alcohol concentrations above 100 mg/dl was sustained in some animals after return to baseline food conditions, and this may have been related to social rank within the groups. Alcohol reinforced drinking of the flavored solutions. Although food deprivation initially produced heavier drinking, drinking with the two protocols was equivalent after return to baseline feeding conditions. These procedures open new opportunities for examining combined social and genetic influences on alcoholic-like drinking. PMID- 3110843 TI - Role of Pavlovian conditioning in the development of tolerance and cross tolerance to the hypothermic effect of ethanol and hydralazine. AB - The role of Pavlovian conditioning in the development of tolerance to the hypothermic effect of ethanol and of cross-tolerance to hydralazine was investigated. In the first study, two groups of rats were treated on alternate days with ethanol (2 or 4 g/kg, respectively, IP) in a novel and distinctive environment (DR). On the non-alcohol days, they received saline in the home room (HR). A control group received saline in both environments. Tolerance to the hypothermic effect of ethanol in the DR was demonstrable in both the 2 and 4 g/kg treatment groups. Tolerance in the HR, however, was observed only in the 4 g/kg treated group. Cross-tolerance to the hypothermic effect of hydralazine was observed for both ethanol-treated groups in the DR but not in the HR. In the second study, ethanol treatment was carried out by daily intubation with 6 g/kg ethanol in the home cage. Tolerance to ethanol-induced hypothermia was demonstrated either in the home cage or in a novel environment. This treatment, however, failed to confer cross-tolerance to the hypothermic effect of hydralazine. These findings suggest that conditioning plays a predominant role in the tolerance produced by low but not by high treatment dosage. The data also suggest that conditioning might be a separate component in tolerance development, which is of special importance in tolerance to behavioral effects in the whole animal rather than to cellular or molecular effects. PMID- 3110844 TI - Antagonism of the stimulant and depressant effects of ethanol in rats by naloxone. AB - The action of naloxone (0.5 and 2 mg/kg IP) on the behavioural effects of a low (2 g/kg PO) and a high dose (4 g/kg PO) of ethanol was studied in rats. Ethanol at the low dose increased spontaneous motility, enhancing open-field external ambulations and reducing shuttle-box latency. All these effects were antagonized by naloxone. Ethanol at the high dose produced by hypomotility, decreasing open field external ambulations and impairing shuttle-box performance. In this case, naloxone also reduced the ethanol effect, but its action was less consistent. Therefore, although mechanisms other than a specific opioid receptor blockade by naloxone must be considered, an involvement of opioid peptides in the effects of ethanol cannot be discounted. PMID- 3110845 TI - Does DGAVP influence memory, attention and mood in young healthy men? AB - The influence of an increasing dose of the vasopressin-like peptide DGAVP (desglycinamide-arginine-vasopressin) on memory was investigated in two groups of ten healthy male volunteers to provide information about the hypothesis of improvement of memory by vasopressin. At the same time we evaluated the effect of DGAVP on mood, alertness or sleepiness in a double-blind placebo-control design. The treatment group received at 9.15 a.m. intranasally a daily increasing dose from 0.1 mg at day 1 to 10.0 mg at day 5. DGAVP did not significantly affect any measure of memory or alertness. DGAVP did, however, produce a significant increase in concentration level and mood. The results of the present study provide no support for the vasopressin theory of memory improvement; rather, the results direct the attention to attention modulating effects. PMID- 3110846 TI - Naloxone and beta-endorphin alter the effects of post-training epinephrine on memory. AB - These experiments examined the involvement of opioid peptides in the memory modulating effects of post-training epinephrine (Epi). Mice were trained on inhibitory avoidance (IA) and Y-maze discrimination (YMD) tasks and given post training injections followed by retention tests 24 h later. In the IA task retention was enhanced by low doses of Epi and impaired by high doses. In both tasks, naloxone facilitated retention and blocked the memory-impairing effects of Epi. These findings are consistent with other evidence suggesting that the memory impairing effects of beta-endorphin are mediated by the release of opioid peptides. Previous studies have shown that a novel exploratory experience given 1 h prior to training blocks the release of brain beta-endorphin and blocks the memory-enhancing effects of post-training naloxone. In the present study we found that a novel experience given 1 h prior to training blocked the memory-impairing effect of post-training Epi otherwise obtained in both tasks. The effects of a low, memory-enhancing dose of Epi appear not to involve the release of opioid peptides: a low dose of Epi blocked the memory-impairing effect of beta endorphin. Further, low doses of Epi and naloxone, which were ineffective when administered alone, significantly enhanced retention when administered together. We interpret these findings as indicating that the memory-enhancing and memory impairing effects of Epi are mediated by different mechanisms. PMID- 3110847 TI - Endurance training effects on striatal D2 dopamine receptor binding and striatal dopamine metabolites in presenescent older rats. AB - Endurance training is associated with higher binding of 3H-spiperone to striatal D2 dopamine receptors of rats sacrificed 48 h following the last exercise bout (Gilliam et al. 1984). In the present study we investigated the effects of endurance training in presenescent older rats on the relationship between steady state levels of DA and its metabolites in striatum versus the affinity and density of striatal D2 DA receptors. Citrate synthase activity of the gastrocnemius-plantaris muscle was 29.06 +/- 2.27 mumole/g wet wt in 21-month-old trained rats versus 22.88 +/- 1.13 mumole/g wet wt in 21-month-old untrained animals. DOPAC levels and DOPAC/DA ratios were greater in the old controls. Endurance training was associated with lower DOPAC levels in the 21-month-old animals. Thus, endurance training may postpone selectively changes in DA metabolism over a portion of the lifespan. As expected, the number of D2 DA binding sites was reduced with age (6 months Bmax:429 +/- 21 fmoles/mg protein; 21 months:355 +/- 20) with no change in affinity. The Bmax of old runners was significantly higher (457 +/- 38 fmoles/mg protein) than that of old controls. Thus, endurance training appears to exert a protective effect on D2 dopamine receptors during the lifespan. Taken together, the present results suggest that there may be a possible reciprocal relationship between changes in DA metabolites and DA binding as a function of exercise in presenescent older rats, and that endurance training may decelerate the effects of age both on nigrostriatal dopamine neurons and on striatal D2 dopamine receptors during a portion of the lifespan. PMID- 3110848 TI - Effects of amphetamine on local cerebral metabolism in normal and schizophrenic subjects as determined by positron emission tomography. AB - The effects of d-amphetamine (0.5 mg/kg PO) on regional cerebral glucose utilization were measured with Positron Emission Tomography (PET). Subjects included ten chronic schizophrenics and six controls who received amphetamine, and six chronic schizophrenics and nine controls who received placebo or no treatment. Amphetamine decreased glucose metabolism in all regions studied (frontal, temporal, and striatal) in normal and schizophrenic subjects. The metabolic effects of amphetamine were correlated with plasma level of the drug. Cortical atrophy was associated with a blunted metabolic response. PMID- 3110849 TI - DSP4 alters the effect of d-amphetamine on variable-interval performance: analysis in terms of Herrnstein's equation. AB - The effect of d-amphetamine (0.1-3.2 mg/kg) on performance in variable-interval 1 min and variable-interval 12-min schedules of positive reinforcement was examined in ten rats treated with the selective noradrenaline neurotoxin DSP4 and 12 control rats. In the control group d-amphetamine had a dose-dependent suppressant effect on response rates maintained under variable-interval 1-min; under variable interval 12-min, response rates were increased by low doses and suppressed by higher doses of the drug. In the case of both schedules, lower doses of d amphetamine were more suppressant and higher doses less suppressant in the DSP4 treated group than in the control group. The levels of noradrenaline in the parietal cortex, hippocampus and cerebellum (determined by high-performance liquid chromatography) were reduced to approximately 15% of control levels in the DSP4-treated rats. The results indicate that treatment with DSP4 attenuated both the facilitatory and the suppressant effects of d-amphetamine on variable interval performance. A formal model couched in terms of Herrnstein's (1970) equation is put forward to account for these results. It is suggested that the noradrenergic pathways emanating from the locus caeruleus are involved in both the facilitatory and suppressant effects of d-amphetamine on operant behaviour. PMID- 3110850 TI - Alcohol consumption in free-feeding rats: procedural, genetic and pharmacokinetic factors. AB - Voluntary consumption of alcohol by rats (i.e. in the absence of food or water deprivation, sweetening of the alcohol solution, etc.) that results in the attainment of behaviorally significant or pharmacologically detectable blood alcohol levels (BALs) has been difficult to demonstrate. In this study, we showed that free-feeding Wistar rats given access to increasingly concentrated solutions of alcohol in separate "drinking" cages on a 1-h per day basis drank on average close to 1 g/kg, resulting in average BALs close to 50 mg%. This drinking was comparable to that obtained by rats trained according to a procedure used widely by others in which animals are maintained at reduced body weights. Weight restriction alone, however, did not enhance amount of alcohol consumption over that of free-feeding animals in the 1-h session. There was also a strain difference in that Wistar rats drank significantly more than did Sprague-Dawley rats. Post hoc absorption curves showed that the initial absorption of alcohol from both the stomach and the peritoneum was slower in Wistar than in Sprague Dawley rats, suggesting rate of absorption may be inversely related to amount of alcohol consumed; metabolic rates and volumes of distribution appeared unrelated to consumption. This periodic availability paradigm might be useful to investigate the effect of biological variables on individual bouts of alcohol consumption. PMID- 3110851 TI - Effects of pimozide on sucrose consumption and preference. AB - The effects of pimozide on sucrose intake were examined, in a two-bottle preference test (sucrose versus water), and in single-bottle tests at five different sucrose concentrations. In the two-bottle test, pimozide dose dependently decreased sucrose intake but increased water intake. In the single bottle test pimozide decreased sucrose intake at low concentrations but had no effect at high concentrations. The results support a role for dopamine in mediating the rewarding effect of sucrose. PMID- 3110852 TI - Do some antidepressants promote suicide? PMID- 3110853 TI - A double-blind trial of bupropion in children with attention deficit disorder. PMID- 3110854 TI - Clonazepam in the treatment of panic disorder and agoraphobia. PMID- 3110855 TI - Psychopharmacology of anxiety disorders: on the role of serotonin in the treatment of anxiety states and phobic disorders. PMID- 3110856 TI - Treatment of bulimia with lithium: a preliminary study. PMID- 3110857 TI - Newer antidepressants in the treatment of bulimia nervosa. PMID- 3110858 TI - CT and MRI of orbital abnormalities in neurofibromatosis and selected craniofacial anomalies. AB - This article begins with a discussion of normal orbital anatomy and the terminology involved in the description of abnormalities of the orbit. Case reports of patients with neurofibromatosis or with a craniofacial anomaly are presented, and the characteristic orbital findings on both CT and MRI are reviewed. Thus the radiologist's role and the value of CT and MRI in the overall treatment of these often complex abnormalities are elucidated. PMID- 3110859 TI - [Pulmonary reaction to radiation as depicted in chest x-rays following megavolt therapy of breast cancer]. AB - X-ray radiographs of the thorax of 184 patients with carcinoma of the breast (treatment period 1974-1978) that were taken during radiotherapy and follow-up were examined with respect to X-ray substrate, intensity, and temporary pulmonary reaction to radiotherapy. The therapy applied was "extended-field" irradiation (5 field technique) via 4 MeV linac with total doses of 50-60 Gy and a fractionation of 5 X 2 or 4 X 2.5 Gy/week. After a characteristic latency period of 11-13 weeks without radiomorphological reactions, the first signs of pneumonitis could be observed (stage I); after 14-19 weeks, florid pneumonitis (stage II A) was noted and from week 16 to 21, florid pneumonitis with first signs of regression (stage II B) was observed. After a transitional period (stage III), the pulmonal radioreaction ended with stationary local fibrosis (stage IV). The radioreaction was classified into three stages of severity: "light" regional pneumonitis and fibrosis occurred in 20% and 39% of the cases; a "medium" one occurred in 5% and 6%; and a "severe" reaction was observed in 12% and 4% of the cases. Further expansion of mediastinal or parenchymal areas of shadow after stage II B does not correspond to the dynamic course of pulmonary radioreactions; in these cases, thoracic tumor progression or metastasis must be assumed. PMID- 3110860 TI - Thrombolytic therapy with recombinant human tissue-type plasminogen activator: a comparison of two doses. AB - The efficacy and safety of two doses of recombinant human tissue-type plasminogen activator (rt-PA) were compared. Forty patients with peripheral arterial occlusions were treated with intraarterial rt-PA. Group A (n = 21) received 0.1 mg/kg/h, and group B (n = 19) received 0.05 mg/kg/h. Infusion durations varied from 4 to 8 hours. Complete thrombolysis occurred in 20 of 21 patients (95%) in group A and in all 19 patients (100%) in group B. In group A, fibrinogen levels were greater than 75% of baseline in ten of 21 patients (48%) at infusion termination. In group B, fibrinogen levels were greater than 75% of baseline in 12 of 19 patients (63%) at infusion termination. Three of 40 patients (7%) had significant complications resulting from rt-PA infusion. The results demonstrate that over similar infusion times, a dose of 0.05 mg/kg/h is as efficacious and results in less systemic fibrinogenolysis than a dose of 0.1 mg/kg/h. PMID- 3110861 TI - The effect of ethanol on arachidonic acid metabolism in the murine peritoneal macrophage. AB - Exposure to ethanol in man has been linked to an alteration of the immune surveillance system and reduced ability of the macrophage to undergo phagocytosis. Since ethanol has been suggested to alter membrane function and inhibit the production of calcium ionophore stimulated synthesis of prostaglandins and leukotrienes by the human neutrophil and transformed murine mast cell, the dose response effect of ethanol on the biosynthesis of icosanoids by the peritoneal macrophage during zymosan phagocytosis was studied. Peritoneal macrophages from two inbred strains of mice derived from a common stock (HS) and selected for sensitivity to ethanol (short sleep [SS]/long sleep [LS]) were studied. Zymosan phagocytosis was found to lead to synthesis of LTC4 (70 ng/10(6) cells), 6-keto-PGF1 alpha (5 ng/10(6) cells) and PGE2 (3 ng/10(6) cells). For the HS macrophage, ethanol caused a dose dependent inhibition of these lipid mediators as well as inhibition of phagocytosis and release of beta hexosaminidase. However, a difference was observed in arachidonate metabolism stimulated by phagocytosis between the LS and SS mice below 100 mM ethanol. The SS mouse had a 50% inhibition of cyclooxygenase products at 86 mM ethanol with no inhibition of lipoxygenase metabolites. The LS mice had a trend suggesting increased lipoxygenase metabolites below 100 mM ethanol. At these levels of ethanol which can be found in man, these results suggest there may be differential production of lipid mediators under genetic control. PMID- 3110862 TI - Formation of cysteinyl-containing leukotrienes by human arterial tissues. AB - Human arterial rings incubated in modified Tyrode solution released small amounts of leukotriene (LT) C4-like material spontaneously and larger amounts upon stimulation with the ionophore A23187 as determined by radioimmunoassay. By reversed phase high pressure liquid chromatography (HPLC) LTC4-like material was found to comigrate with authentic LTC4, LTD4 and LTE4. Nordihydroguaiaretic acid (NDGA) significantly inhibited the ionophore A23187-induced release of LTC4-like material, while indomethacin was without effect. Simultaneously the arterial rings released much larger amounts of 6-keto-prostaglandin (PG) F1 alpha, which were significantly decreased by indomethacin. The results demonstrate that human arterial tissue has the capacity to synthesize cysteinyl-containing LT from endogenous arachidonic acid. PMID- 3110864 TI - Registered nurses: are you selling yourself and your profession short? PMID- 3110863 TI - Eicosadiynoic acid: a non-toxic inhibitor of multiple enzymatic steps in the production of icosanoids from arachidonic acid. AB - We have studied the acetylenic fatty acid 20:2 delta 8a, 11a (eicosadiynoic acid, EDYA). It was found that this compound acts as an inhibitor of several steps in the production of icosanoids from arachidonic acid. First, the compound was shown to inhibit arachidonate uptake by platelets. Second, using a detergent solubilized preparation from calf brain, EDYA was found to inhibit both the arachidonoyl and the non-specific long chain acyl-CoA synthetase, which convert arachidonate to its CoA ester. Third, the compound decreased the conversion of dihomo gamma linolenic acid to arachidonate in the mouse fibrosarcoma HSDM1C1 cell line, acting as an apparent delta 5 desaturase inhibitor. Finally, EDYA (50 microM) inhibited cyclooxygenase activity. The compound was not toxic to cultured cells. Cells were grown for months in tissue culture medium at concentrations as high as 50 microM, with no morphologic changes by light microscopy and no prolongation of the doubling time over untreated cells. Our findings with this compound indicate that it limits icosanoid production by inhibiting cyclooxygenase and also by limiting arachidonate uptake, activation, and production from precursor fatty acids. PMID- 3110865 TI - Nurses' back injuries: what do we know and what can be done to prevent them? PMID- 3110866 TI - Renal scintigraphy using indium-111 oxine-labeled autologous leukocytes in renal transplant recipients. PMID- 3110867 TI - Locally advanced uterine cervical cancer: our experience on 102 cases. PMID- 3110868 TI - Solitary diverticulum or blind branch of a bifid ureter? Presentation of a case with associated multicystic kidney. PMID- 3110869 TI - Acquired diverticulosis of the small bowel. PMID- 3110870 TI - [Thermal effects of medical lasers on endodontic tissue. Quantitative in vitro study]. PMID- 3110871 TI - [Evaluation of pulp-dentin response to carbon dioxide laser exposure: physiology histopathology]. PMID- 3110872 TI - Chemical spill exposure assessment. AB - POSSM, the PCB On-Site Spill Model, is a contaminant transport model developed to predict environmental concentrations associated with a chemical spill. The model predicts daily changes in chemical concentrations on a spill site (e.g., in soil and on vegetation) and losses of chemical due to volatilization, surface runoff/soil erosion, and leaching to groundwater. Spill areas consisting of soil/vegetation and/or an impervious surface (e.g., asphalt and concrete) can be analyzed, as can different spill cleanup practices. POSSM is used to analyze exposure levels associated with a hypothetical capacitor spill. While the model was developed for PCB spills, it is generally applicable to a number of organic compounds. PMID- 3110873 TI - The spread of a PCB spill on a soil surface. AB - Determining the fate of an oil spill on soil is often the first step in analyzing the risks of human exposure to hazardous viscous liquids such as PCBs. The special surface properties of rigidity and porosity are not among the boundary conditions in previous analyses of spills on water. The present work solves the expressions of mass and momentum conservation using a perturbation approach. Using the example of an Aroclor 1254 spill to illustrate the approach, we find that the radius at the halt of spreading is roughly proportional to spill volume for large spills. Spreading halts when the infiltration equals the spill volume. The radial distribution of infiltration decreases gradually from its central maximum, but falls suddenly to zero approaching the outer edge. Sample results are plotted for Aroclor 1254 spills from 4 to 21 liters in volume. PMID- 3110874 TI - An analysis of the de minimis strategy for risk management. AB - A de minimis risk management strategy sets a threshold so that risks below the specified level are defined as trivial and exempted from further consideration. The intended purpose is to help avoid inappropriate and wasteful concern with insignificant low-level risks. In most instances a de minimis strategy is likely to have beneficial or innocuous effects, but under certain circumstances large differences may develop between nominal and actual de minimis levels. The potential for such discrepancies illustrates why de minimis (and all other risk management) strategies should be evaluated on the basis of the portfolio of risks that would accumulate from applying such strategies over time, rather than on the apparent reasonableness of any single instance of application. PMID- 3110875 TI - Comparative fire risk study of PCB transformers. AB - A risk assessment comparing the acute effects of mineral oil and PCB-askarel dielectric fluids in two transformer sites was performed. The first site has the installation characteristics for a PCB-askarel-filled transformer with sprinkler fire protection. A risk comparison is made between two types of transformers (PCB askarel-filled and mineral oil-filled) for this site. The second site (a vault) has the installation characteristics for a mineral oil-filled transformer, and a risk comparison is made in a fashion similar to the first site. Risk is expressed in terms of frequencies of one or more acute injuries or fatalities per transformer year. PMID- 3110876 TI - [Alpha-heavy chain disease. Apropos of a case]. PMID- 3110877 TI - [Von Recklinghausen's neurofibromatosis and ampulloma]. PMID- 3110878 TI - [Refractory cardiac insufficiency and paraproteinemia in a 71-year-old woman]. PMID- 3110879 TI - [Cerebral edema complicating diabetic ketoacidosis]. PMID- 3110880 TI - [Changes in serum cholinesterase in schistosomiasis mansoni]. PMID- 3110881 TI - [Graphic model for analyzing the profitability of anti-hepatitis B vaccination by simulation of prevention campaigns]. PMID- 3110882 TI - [GH and PRL after TRH and hpGRF(1-40) administration in 2 cases of acromegaly with hyperprolactinemia]. PMID- 3110883 TI - [Occurrence of viral hepatitis in cardiac surgery patients]. PMID- 3110885 TI - Morphological changes in the renal macula densa during natriuresis and diuresis. AB - Morphological changes in the macula densa have been studied during the infusion of diuretic agents into the renal artery of anesthetized dogs. The kidneys were fixed by rapid high pressure perfusion with glutaraldehyde. Large basolateral intercellular spaces were seen between macula densa cells in control kidneys, but the number and extent of these spaces were strikingly reduced during the natriuresis and diuresis induced by the infusion of frusemide, ethacrynic acid or mannitol. Natriuresis and diuresis produced by the intravenous infusion of large volumes of 0.9% NaCl solution also resulted in closure of these spaces. No simple relationship existed between changes in plasma renin activity and closure of the spaces between macula densa cells during these procedures. A distinctive, membrane-bound, vesicle-containing structure was identified between the basolateral processes of the cells of each macula densa; the function of this structure awaits elucidation. We suggest that changes in the size of the basolateral intercellular spaces of the macula densa reflect changes in fluid flux between the distal tubule and the interstitium of the juxtaglomerular apparatus. PMID- 3110884 TI - Effect of carbonic anhydrase inhibition on (U-B)pCO2 in the alkaline urine of the rabbit. AB - We studied factors influencing urine pCO2 minus blood pCO2 [(U-B)pCO2] in rabbits infused with sodium bicarbonate solutions. Unlike other species, the rabbit does not develop a significant (U-B)pCO2 (urine pCO2 greater than blood pCO2) after alkali or acid buffer infusion. However, intravenous acetazolamide immediately induced a significant (U-B)pCO2. The effect could not be related to the blood pH or pCO2, the urinary concentration of bicarbonate or inorganic phosphate, or to changes in plasma potassium concentration. Methazolamide was also effective in increasing (U-B)pCO2. This significant (U-B)pCO2 was present after carbonic anhydrase inhibition in rabbits subjected to chronic partial obstruction of urinary flow and in rabbits treated with 11-desoxycorticosterone acetate (DOCA). We propose that carbon dioxide is normally dissipated from the alkaline urine of the rabbit by a distal tubular mechanism, which involves catalytic conversion of carbon dioxide to bicarbonate. Inhibition of carbonic anhydrase leads to the formation of a significant (U-B)pCO2. In the rabbit, pCO2 may be an index of collecting duct acidification under certain circumstances; however, the relation of collecting duct acidification to the high (U-B)pCO2 during the inhibition of carbonic anhydrase remains to be determined. PMID- 3110886 TI - Effect of encainide on in vivo drug metabolism in the rat. AB - The effect of encainide, an investigational antiarrhythmic, on drug metabolism was examined using the model substrate antipyrine. Administration of a single oral dose of encainide hydrochloride 100 mg/kg one hour prior to antipyrine administration resulted in a mean 30% reduction in antipyrine clearance. These data indicate that encainide, like other agents subject to substantial first-pass metabolism, is capable of inhibiting oxidative drug metabolism. PMID- 3110887 TI - Alveolar-capillary diffusion of oxygen in dogs exercising in hypoxia. AB - To detect and quantify diffusion limitation in alveolar-capillary O2 transfer, measurements of pulmonary gas exchange were performed in 6 awake, chronically tracheostomized dogs (mean body weight 28.3 kg) breathing low O2 (arterial PO2 35 39 Torr), with or without CO2 added to inspired gas. From rest to exercise, with O2 uptake averaging 23 ml/(min X kg), the ideal-alveolar-to-arterial PO2 difference (PAiO2-PaO2) increased from 2.1 +/- 0.2 Torr (mean +/- SE) to 2.9 +/- 0.2 in hypoxia, and from 1.9 +/- 0.7 Torr to 3.0 +/- 0.5 in hypercapnic hypoxia. The apparent pulmonary O2 diffusing capacity (DLO2), calculated from O2 uptake, mixed-venous PO2, arterial PO2, and ideal-alveolar PO2, was found to be increased by hypercapnia and exercise. During exercise DLO2 averaged 74 ml/(min X Torr) in hypoxia and 76 ml/(min X Torr) in hypercapnic hypoxia. Because of the influence of inhomogeneity effects, these values should be considered as minimum values for the true pulmonary O2 diffusing capacity. When compared to the pulmonary CO diffusing capacity (DLCO) previously determined by C18O rebreathing in the same dogs in similar conditions, the DLO2/DLCO ratio averaged 1.2, thus being in accordance with the value predicted from the corresponding Krogh diffusion constant ratio. It is concluded that the DLO2 and DLCO values determined drug exercise in hypoxia may be considered to represent acceptable measures for alveolar-capillary diffusion conductance of lungs. PMID- 3110888 TI - Alteration of lung mechanics by protein-calorie malnutrition in weaned rats. AB - The influence of protein-calorie malnutrition on lung development was studied in weaned rats. From the age of 28 days, they received ad libitum a diet containing 15 or 5% proteins (P15 or P5) or half of the high-protein diet (1/2 P15). After one month, lung weight and lung protein and DNA content were decreased in test animals, but DNA concentration was increased. These lungs appeared to have a higher density of smaller cells. V-P curves were performed on excised lungs. With air-filling, the curves obtained in 1/2 P15 and P5 rats were shifted downward and to the right even when expressed as percent of maximal volume. Their exponential analysis assessed the decrease in compliance. With saline-filling, V-P curves were similarly shifted except at low volumes. Both in P5 and 1/2 P15 rats, the pressure at lung rupture after air- or saline-filling was increased. In conclusion, protein-calorie malnutrition started after weaning interferes with lung development, causing an increase in surface and tissue elastic forces and in resistance to rupture. PMID- 3110889 TI - Effects of graded exercise on blood gas tensions and acid-base characteristics of rainbow trout. AB - A swim tunnel respirometer and an extracorporeal blood circulation technique allowed continuous collection of data from exercising fish below and near their critical speed. Swimming at speeds below maximum showed no changes in plasma Na+, Cl- and lactate concentrations but increased levels of blood hemoglobin and plasma K+. PaO2 and PaCO2 showed an exponential decrease and increase respectively and related to swimming speed. Increased swimming speed changed the acid-base status toward a mixed respiratory and metabolic acidosis. Upon reaching maximum speed sudden and large increases in plasma Na+, K+ and lactate concentrations occurred associated with a large metabolic acidosis. PMID- 3110890 TI - Respiratory and upper airway responses to nasal obstruction in awake lambs and ewes. AB - The aims of this study were to compare the ability of awake newborn lambs and adult sheep to breathe orally when the nasal route was blocked and to determine the means by which it was accomplished. Chronic EMG electrodes (diaphragm, genioglossus, geniohyoid, posterior crico-arytenoid, digastric, thyroarytenoid) and fibre-optic catheters were implanted in 10 lambs and 4 ewes. Before each study soft tubes were fixed into the nostrils allowing rapid blockade of the nasal ventilatory pathway. During nasal blockade inspiratory upper airway dilator EMG activity increased. SaO2 fell until mouth opening occurred, then returned to near control values; oral breathing then ceased leading to desaturation again. In lambs and ewes there was significant hypoxia, hypercapnia and acidaemia. In lambs 2-14 days old, PO2 and pH fell to lower levels than in older lambs (15-30 days) or ewes and PCO2 rose more. In lambs PCO2 gradually increased during the period of obstruction. We conclude that maintenance of blood gas homeostasis in newborn lambs is more severely impaired by nasal obstruction than in older lambs or ewes, possibly due to an immaturity of neural mechanisms controlling the creation of an oral airway. PMID- 3110891 TI - Effects of H+ versus CO2 on ventilation in the Pekin duck. AB - Measurements were made of ventilation (VE) and arterial blood gases (PCO2 and PO2) and pH in awake Pekin ducks, Anas platyrhynchos, exposed to sequential cycles of 1% step changes in inspired CO2 from 0 to 5 and back to 0% CO2, as well as to a sustained period (5 h) of 5% CO2 breathing. Changing the background level of inspired PO2 was used to alter the range of PaCO2 over which CO2 response curves were obtained. The initial increase in minute ventilation following a sustained step increase in inspired CO2 (5%) began to decline immediately at a rate of approximately 1% every 5 min. This was closely paralleled by increases in both pH and [HCO-3] while arterial PaCO2 remained constant or increased slightly. CO2 response curves (VE vs PaCO2) generated in a sequential fashion shifted down and to the right (a paradoxical decrease in VE associated with an increase in PaCO2) while the relationship between VE and pH remained constant. These data suggest that VE is a single function of pH in birds under these conditions and that the relationship between VE and PaCO2 is altered due to metabolic acid-base compensation even during acute CO2 exposure. PMID- 3110892 TI - Acid-base status immediately following rapid changes of alveolar gas composition in awake dogs. AB - To study the interrelationship between blood O2, CO2, and acid-base status during rapid changes of alveolar gas composition unanesthetized dogs were made to inhale high CO2 gas mixtures following air breathing or to rebreathe high CO2 and O2 mixtures following hypoxia. Before and immediately after each change in alveolar gases, sequential blood samples were taken from the carotid artery for measurement of pH, PCO2 and PO2. In the experiments at normoxia the calculated base excess (BE) decreased by about 0.7 mmol/L after 10 sec and then returned to baseline level. A smaller decrease (averaging 0.4 mmol/L) was found with hyperoxia following hypoxia. The changes in BE can be attributed to bicarbonate (or H+) exchange between blood and tissue. Lung tissue is probably responsible for the rapid initial change in BE. PMID- 3110893 TI - Epidemiology and pathophysiology of Neisseria gonorrhoeae infection. PMID- 3110894 TI - Medical and biologic aspects of adolescent depression. PMID- 3110895 TI - Sertoli cell only syndrome: a variant of testicular germinal cell absence. PMID- 3110896 TI - Osteomalacia and bone disease arising from aluminum. PMID- 3110897 TI - [von Willebrand's disease: study of 58 patients]. PMID- 3110898 TI - [Gastrointestinal hemorrhage in hemophilia: study of 110 patients]. PMID- 3110899 TI - [Prophylactic use of antibiotics in surgical practice]. PMID- 3110900 TI - [Malnutrition in puerperal women of the northern area of Santiago, Chile]. PMID- 3110901 TI - [Comparison of office, long-term and home blood pressure determination]. PMID- 3110902 TI - [Pseudo-hypertrophic pelvi-crural amyloid myopathy in lambda light-chain myeloma. Clinical, morphological and immunocytochemical study]. AB - The case of 65 year old woman with progressive enlargement and "wooden" induration of the pelvic girdle and thigh muscles due to an amyloid infiltration is reported. Muscle changes appeared two years after a diagnosis of myeloma with free lambda light chains. The patient complained of muscle pain, lassitude and weakness. Macroglossia was present. Skeletal muscle (vastus lateralis) contained large amounts of amyloid substance and showed type 2B atrophy. There was no fiber type grouping. Some amyloid deposits abutted on the muscle fiber, destroyed the basal lamina and sarcolemma, but never infiltrated it. Besides the amyloid phagocytosis by macrophages, a relationship between amyloid filaments and fibroblasts was present. Another non-congophilic substance was revealed using the Avidin-Biotin peroxidase complex to localize lambda light chains by light microscopy and corresponded to a granular substance in electron microscopy. Clinicopathological results are discussed with a review of thirteen similar cases previously reported. PMID- 3110903 TI - [Subsidies for the new concept of the indeterminate form of Chagas' disease ]. PMID- 3110904 TI - [Evaluation of the permeability of distal splenorenal anastomosis, by ultrasonography and angiography in hepatosplenic form of schistosomiasis mansoni]. PMID- 3110906 TI - [Extended corticotherapy]. PMID- 3110907 TI - [Schistosoma mansoni: experimental infection in mice through the ear and quantification of the parasitism in the skin]. PMID- 3110905 TI - [Clinical and therapeutic study of 13 cases of gonococcal arthritis]. PMID- 3110908 TI - Splenomegaly in relation to Schistosoma mansoni egg counts: a population based study (1). PMID- 3110910 TI - [Boredom as a marking event]. PMID- 3110911 TI - [Organization of an antidiabetic center]. PMID- 3110909 TI - Sensibility of different larval stages of Schistosoma mansoni to the larvae disappearing reaction (LDR) in murine schistosomiasis (1). PMID- 3110912 TI - [Computerized nursing records]. PMID- 3110913 TI - [Experimental project of planning the social rehabilitation of former drug addicts]. PMID- 3110914 TI - [The aged hospitalized patient: problems and suggestions]. PMID- 3110915 TI - [Occupational accidents during urban refuse collection. Experiences during territorial apprenticeship of a group of nursing students]. PMID- 3110916 TI - [Clinical pharmacology and therapy 1985-1986]. PMID- 3110917 TI - [Learning from leprosy: a look at immunology and the Third World]. PMID- 3110918 TI - [Intravenous infusions in nursing care]. PMID- 3110919 TI - [Central position of the physician or the patient?]. PMID- 3110920 TI - [Formation of an integrated program for the 1st year of courses for pediatric nurses]. PMID- 3110921 TI - [Reorganization of the apprenticeship for the 1st year of courses for pediatric nurses]. PMID- 3110922 TI - [Nursing in acute alcoholism: approach to problems]. PMID- 3110923 TI - [Oral hygiene: is there a scientific basis?]. PMID- 3110924 TI - [The organization of home hemodialysis in Italy]. PMID- 3110925 TI - [Eritrea: a forgotten country]. PMID- 3110926 TI - [Instruction and the nursing profession within the framework of international cooperation]. PMID- 3110927 TI - [A course of updating for nurses in neurosurgery]. PMID- 3110928 TI - [Types of preparations for enteral feeding and tube feeding]. PMID- 3110929 TI - [Enteral nutrition and tube feeding]. PMID- 3110930 TI - Epidemiological survey of urinary schistosomiasis in southeastern Mauritania. AB - Nine villages in the Sahelian Western Hodh Region of Mauritania, West Africa, were surveyed for infection with Schistosoma haematobium. A total of 983 subjects were randomly selected (single stage cluster sampling) and they provided specimens. The populations of five villages were highly infected with prevalence rates exceeding 50% among children under 16 years of age and peak prevalences ranging from 75% to 100% for children 6-10 or 11-15 years old. Mean densities of infection reached their peak for the same age classes with geometric means ranging from 28 to 265 eggs/10 ml urine. No difference in prevalence or mean density was found between males and females after age adjustment. Frequency distributions of egg outputs were not random but aggregated. An indirect screening technique, based on urine analysis reagent strip findings, was able to identify 98% of the most infected subjects (greater than or equal to 50 eggs/10 ml urine). PMID- 3110931 TI - Haematuria and proteinuria in urinary schistosomiasis: response to therapy with praziquantel in Tanzanian children. AB - In order to assess the efficacy of praziquantel against Schistosoma haematobium and its effect on the morbidity indices, haematuria and proteinuria, a study was carried out using school receiving praziquantel at 40 mg/kg body weight. Twenty four weeks after treatment, the percentage of cure was high and reached 100% among the 'light' and 'moderate' infection groups. In the 'heavy' infection group, a cure rate of 50% and a 69.3% egg reduction was observed. An overall cure rate of 94% was achieved at 24 weeks. Microhaematuria and proteinuria were reduced by 96.6% and 92.5%, respectively. PMID- 3110932 TI - [Organochlorine pesticides and polychlorinated biphenyls in the adipose tissue of abattoir and game animals from the northern region of Poland, 1984]. PMID- 3110933 TI - Comparative study on the dynamics of the electroencephalographical changes in the petit mal epilepsy during both classical and valproic acid treatment. PMID- 3110934 TI - The effects of drugs and habituation upon the audiogenic seizures in rats. PMID- 3110935 TI - [Sciatica caused by synovial cysts and lumbar articular diverticula with intraspinal development. Saccoradiculographic, computed tomographic and arthrographic study]. AB - The authors report 8 cases of patients with synovial cysts (3 cases) or diverticuli (5 cases) of the lumbar joints, compressing the sciatic roots. They describe the radiological aspects of the two sides of the degenerative pathology of the posterior articular processes, which are relatively unrecognized (14 cases in the literature). They insist on the advantage of saccoradiculography which is the only test to be able to demonstrate dynamic alterations in relation with diverticuli, if performed in a standing position. The authors show the advantage of tomodensitometry which supports the diagnosis of cyst in the presence of a fibrous wall image. They emphasize the value of the arthrography of the posterior joint; it presents a diagnostic role by visualizing the cavities, and a therapeutic role by permitting the injection in situ of steroids and/or local anesthetics. PMID- 3110936 TI - Measurement of colloid osmotic pressure in body fluids: errors caused by preheparinized glass capillaries and by CO2 loss. AB - The effect on colloid osmotic pressure (COP) of heparinizing body fluids was estimated with a low compliant osmometer, using Diaflo PM-30 or PM-10 membranes (Amicon, Lexington, Mass., USA). It was found that collecting and storing samples in preheparinized glass capillaries may increase COP by up to 4.0 mmHg. Measurements on heparin and protein solutions, separately and mixed, show that these macromolecules have a mutually potentiating effect on COP, probably by excluding part of the water as distribution space for the other molecular species. While this 'heparin error' varies among various types and batches of capillaries (Vitrex, Modulohm I/S), the content of heparin in some batches appears to be two to three times greater than the declared minimum. Alternatively, the excess COP may result from addition of other water-soluble macromolecules in the heparinization process. Even if some batches do not give appreciable error, we recommend to avoid preheparinized capillaries for measurement of COP. Both defibrination, and the amount of heparin needed to anticoagulate macro blood samples, have insignificant effect on COP. Loss of CO2 by diffusion from separated plasma may increase pH towards 9.5. Concomitantly, COP increased by 2.1 mmHg per pH-unit. If plasma or serum samples are capped within some minutes after separation, they may be stored for weeks at 4 degrees C in polyethylene tubes without appreciable change of COP. PMID- 3110937 TI - Gas composition of the normal and the ventilated middle ear cavity. AB - Epidemiologic and controlled studies indicate that late minimal hearing impairment is a sequelae after the use of a ventilation tube in early childhood. The patho-physiology is unknown, but abnormal middle ear gas composition might be important. Therefore it is mandatory to measure middle ear gas composition in order to understand the gas exchange in the normal middle ear, as well as the change in gas composition associated with ventilation tubes. Accordingly, the aim of this study was to measure middle ear gas composition both in the physiologic state and in artificial ventilation by a transtympanic tube. Employing puncture of the typanic membrane, through a liquid seal, we aspirated 300 microliters of middle ear gas. The procedure was carried out under the otomicroscope on adults without any anesthesia. A total of 58 normals participated, along with 10 persons with unilateral ventilation tubes and 1 with a patent Eustachian tube. The mean values of physiologic state were: Partial pressure of oxygen in the middle ear cavity = 39 mm Hg, and partial pressure of carbondioxide in the middle ear cavity = 48 mm Hg. The mean values of artificially ventilated ears were: Partial pressure of oxygen in the middle ear cavity = 138 mm Hg, and partial pressure of carbondioxid in the middle ear cavity = 15 mm Hg. The total imprecision was 4.2/4.4 mm Hg and the accuracy seems fair,--especially because we found a quasi equilibrium to the "most probable value", the venous blood gases. It is concluded that artificial ventilation of the middle ear cavity, with a ventilation tube increases the oxygen content of the middle ear cavity with a factor 3.2. This constitutes a relative hyperoxic atmosphere with a subsequent possibility for a toxic tissue damage. PMID- 3110938 TI - Apolipoprotein A-I in liver disease. AB - Apolipoprotein A-I and high-density lipoprotein concentrations in the plasma of patients with liver disease have been found to be either normal or lower than normal. In this study the apolipoprotein A-I concentration was measured in the plasma of 19 patients with cholestatic liver disease and 21 patients with noncholestatic liver disease. To evaluate the severity of liver disease, serum albumin, prealbumin, bilirubin, and bile salts were also measured. Apolipoprotein A-I concentrations in plasma correlated positively with serum albumin (r = 0.55, p less than 0.001) and prealbumin (r = 0.57, p less than 0.001) and negatively with serum bilirubin (r = -0.47, p less than 0.01) and bile salts (r = -0.54, p less than 0.001). The apolipoprotein A-I level thus seems to reflect the severity of liver disease. This is presumably due to a decreased liver synthesis of apolipoprotein A-I in liver disease. PMID- 3110939 TI - Strip test is reliable in common prevalences of hypolactasia. AB - The object of this study was to compare the indirect diagnostic methods on the basis of urinary galactose determination in the diagnosis of lactose malabsorption with the actual lactase activities. One hundred and seven patients were studied. The specificity and sensitivity of the strip test were 97%. With 30% actual prevalence the positive predictive value was 94%, and the negative predictive value was 99%. In common prevalences of hypolactasia the strip test was reliable. PMID- 3110940 TI - Inhibitory effects of anti-HLA-A, B, C heavy chain and anti-beta 2 microglobulin monoclonal antibodies on alloantigen and microbial antigen-induced immune responses in vitro. AB - The role of HLA class I subunits in class II-restricted immune responses was investigated by means of a panel of monoclonal antibodies (MoAb) recognizing HLA A,B,C heavy chain and different beta 2 microglobulin (beta 2m) epitopes. MoAb against either class I subunit strongly inhibited mixed lymphocyte cultures, generation of cytotoxic T lymphocyte cultures, generation of cytotoxic T lymphocytes or natural killer-like activity, and lymphoproliferation in response to soluble or particulate microbial antigens derived from Candida albicans. In general, anti-beta 2m MoAb were more efficient inhibitors than anti-HLA-A,B,C heavy chain MoAb. The inhibitory effects were specific, in that the parental myeloma ascitic fluid or a low-affinity MoAb against beta 2m, or MoAb directed against non-HLA surface structures did not affect any of the immune responses studied. The MoAb-induced inhibition could not be attributed to nonspecific toxic effects, since PHA-induced blastogenesis and IL-2-dependent proliferation of mixed lymphocyte culture (MLC) blasts were not inhibited. Furthermore, exogenous IL-2 did not reverse the block of MLC and microbial antigen-induced proliferative responses by MoAb. Taken together, these data suggest an involvement of both subunits of class I antigens in class II-restricted immune responses. PMID- 3110941 TI - Induction of proliferation and differentiation of leukaemic B cells from patients with chronic lymphocytic leukaemia by anti-mu and conditioned medium. AB - We investigated the growth and differentiation of leukaemia B cells from patients with B-cell chronic lymphocytic leukaemia (CLL) in response to proliferation and differentiation factors present in conditioned medium and to anti-immunoglobulin antibodies. Highly purified E-rosette negative (E-) B cells from 5 out of 15 patients with CLL exhibited moderate proliferative responses to 10 or 50 micrograms/ml of F(ab)'2 fragments of rabbit anti-human mu-chain specific antibody. Conditioned medium (CM), derived by stimulating human peripheral blood mononuclear leucocytes with PHA, induced significant proliferative responses of purified E- cells in 13 out of 14 patients examined. The extent of these proliferative responses varied substantially, and was in the range of 2.6- to 91 fold. Stimulation of purified E- cells from patients with CLL with both anti-mu and CM resulted in significant proliferation in all 15 patients examined. These responses were significantly higher than those induced by CM alone (P less than 0.02). Synergism between CM and anti-mu in inducing proliferative responses was observed in 11 out of 15 patients. Largely leukaemic B cell populations expressing on the cell surface more than one immunoglobulin heavy-chain isotype, exhibited significantly higher (P less than 0.009) proliferative response to CM and anti-mu than those expressing IgM only. Highly purified E-peripheral blood or tonsil lymphocytes from all normal donors examined responded by proliferation to anti-mu alone or to CM alone. Synergism in inducing proliferative responses was also observed when the cells were stimulated with both CM and anti-mu. In addition to inducing proliferative responses, culture with CM of purified E rosette negative, largely leukaemic, B cells from patients with CLL for 6 days at 37 degrees C resulted in differentiation into immunoglobulin synthesizing and secreting cells. Synthesis and secretion of IgM were observed in 7 out of 10 patients examined. A switch to IgG production was observed in three patients. Morphological examination of E- cells from patients with CLL after treatment with CM demonstrated that these cells were differentiated into plasma-like cells. These results suggest that leukaemic B cells from patients with CLL can be induced to proliferate and differentiate in response to growth and differentiation factors derived by mononuclear leucocytes, in a manner similar to that of normal B cells. PMID- 3110942 TI - Pharmacology of auranofin: overview and update. AB - Auranofin, the only approved oral gold complex of value in suppressing rheumatoid arthritis, differs from injectable gold compounds molecularly and pharmacologically. Although comparably efficacious, the side-effect profiles of oral and intramuscular gold differ, and the withdrawal rate for adverse reactions is several-fold lower with auranofin. Considerably less elemental gold is available to the internal milieu with auranofin than with gold sodium thiomalate (3 mg/week vs. 25 mg/week), a difference reflected in lower blood, synovial fluid and tissue gold levels. Approximately 25% of the administered auranofin dose is absorbed orally, and 85% is recovered in feces. Serum gold levels are 300-400 micrograms/dl one week after injectable gold and 60-70 micrograms/dl daily with auranofin (6 mg/d). But, surprisingly, the fraction of gold associated with the red blood cell fraction is higher with auranofin. Blood gold levels do not correlate with clinical response to treatment or frequency or type of adverse reaction, regardless of the gold preparation used. Similar results obtain with penicillamine. Methotrexate blood levels are not related to the development of hepatic fibrosis. The mechanisms of gold action in rheumatoid arthritis are unknown, despite the laboratory definition of multiple antiinflammatory, immunologic and other effects. Sulfhydryl binding activity, an established property of injectable gold compounds and penicillamine of potential importance pharmacodynamically, is limited with auranofin. PMID- 3110943 TI - Long-term efficacy and safety of auranofin: a review of clinical experience. AB - Auranofin (AF) is the first oral gold therapy developed for the treatment of rheumatoid arthritis (RA). Since the drug was introduced in 1982, more than 100,000 patients have been treated with AF. Controlled clinical trials prior to introduction included more than 5,000 patients, some of whom received AF for more than 7 years. At the recommended dose of 6 mg/day, AF therapy results in a lower total body burden of gold than does injectable gold (IG). However, comparative studies indicate that the clinical effect of AF is comparable to that of IG. Adverse events that occur during AF therapy tend to be mild and of short duration, often resolving with continued therapy or temporarily reduced dosage. Most adverse events occur during the first few months of therapy, and the incidence diminishes over time. Data on 134 patients who received AF for more than 5 years demonstrate a sustained therapeutic effect and no cumulative toxicity from long-term therapy. In 18 comparative trials, 1,053 patients with RA received either AF (527 patients) or IG (526 patients) for up to 36 months. At 1 year, similar proportions of patients in the AF and IG groups had 50% or greater improvement in various parameters of disease activity. Safety analysis showed that AF was significantly better tolerated than IG. The rate of withdrawal because of adverse events was about twice as great in the IG group as in the AF group, both at one year (14% vs. 31%, p less than 0.05) and for the duration of the trials (18% vs. 34%, p less than 0.05). This suggests that the benefit-to risk ratio is more favorable with AF. PMID- 3110944 TI - Comparison between sodium aurothiomalate and auranofin in rheumatoid arthritis. Results of a two-year open randomized study. AB - We compared the effectiveness of Auranofin, and sodium aurothiomalate (SATM) given for 2 years to patients with rheumatoid arthritis. This was an open trial with randomized entry to 2 treatment groups of 60 patients each. Only 40% of patients completed 2 years of treatment but these showed significant improvement in their indices of disease activity. Adverse reactions were a more common reason for withdrawal from SATM than from Auranofin, while insufficient therapeutic response was more common with Auranofin. This study also shows that inefficacy, toxicity, complicating illnesses, and lack of compliance limit the beneficial outcome of long-term chrysotherapy. PMID- 3110945 TI - The prevalence and clinical associations of the lupus anticoagulant in systemic lupus erythematosus. AB - To determine the prevalence and clinical associations of the lupus anticoagulant (LAC) in patients with systemic lupus erythematosus (SLE), we studied 74 patients with SLE, 6 with lupus-like disease and a heterogeneous group of 45 patients with various autoimmune diseases. LAC was demonstrated in 19 SLE patients (26%), 5 patients with lupus-like disease (83%) and in none of the other patients. Statistically significant associations were found between LAC and a history of thromboembolic events (p less than 0.001), fetal loss (p less than 0.001), thrombocytopenia (p less than 0.01), biologically false-positive VDRL test (p less than 0.02) and convulsions (p less than 0.05). A negative correlation was found between LAC and a history of butterfly rash (p less than 0.01) and the presence of antibodies against extractable nuclear antigen (p less than 0.01). No significant difference was found between LAC-negative SLE patients and patients with other autoimmune diseases with respect to the prevalence of thromboembolic events or fetal loss. We conclude that LAC is a useful marker to identify a subset of patients with SLE or lupus-like disease at risk of thromboembolic events, fetal wastage, and thrombocytopenia. PMID- 3110946 TI - Immunodeficiency syndrome associated with aurothiomalate treatment in a patient with rheumatoid arthritis. PMID- 3110947 TI - Polychlorobiphenyls (PCBs), polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans (PCDFs) in human milk, blood and adipose tissue. AB - Persistent and toxic chemicals such as polychlorinated biphenyls, dibenzo-p dioxins and dibenzofurans are able to accumulate in human tissues, especially in fats. In recent years PCBs have frequently been detected in human milk, blood and adipose tissue from the general population and levels in different tissues correspond to the fat content of the samples. In recent years the very rapid development of analytical methods and the lowering of detection limits have resulted in the detection of PCDDs and PCDFs in human tissues from the general population. The levels of PCBs are approximately 10,000 times higher than the sum of the levels of PCDDs and PCDFs, but the latter substances are much more toxic. Accidental or occupational exposures have resulted in much higher tissue levels in exposed individuals than in the general population. The relatively high levels in breast milk result in very high daily intakes of such chemicals by breast-fed infants, and a potential hazard to this risk group. The origin of the residues seems mainly to be environmental pollution from waste disposal, incineration or other high-temperature operations. PMID- 3110948 TI - FDA puts new heart drug on hold. PMID- 3110949 TI - Companies vie over new heart drug. PMID- 3110950 TI - Detection of minimal residual cells carrying the t(14;18) by DNA sequence amplification. AB - By means of the polymerase chain reaction (PCR) technique, DNA sequences were amplified that flank the crossover sites of a characteristic chromosomal translocation for follicular lymphomas, t(14;18)(q32;q21). This technique permitted the detection of cells carrying the t(14;18) hybrid DNA sequences at a dilution of 1:100,000. The remission marrow and blood samples of a patient with follicular lymphoma and the t(14;18) failed to show any abnormality by morphological examination and conventional Southern blot analysis. However, the t(14;18) hybrid DNA sequences were detected by the PCR technique. Thus, this technique is a highly sensitive tool to detect minimal residual cells carrying the t(14;18) and has the potential to identify a subpopulation of patients with subclinical disease. PMID- 3110951 TI - Ruling on heart drug may boost research. PMID- 3110952 TI - TPA and PDQ. PMID- 3110953 TI - Asymmetry of neural feedback in the organization of behavioral states. PMID- 3110954 TI - Eosinophils cocultured with endothelial cells have increased survival and functional properties. AB - Human peripheral blood eosinophils, cells often associated with allergic and parasitic diseases, were maintained in vitro for at least 14 days when they were cocultured with bovine endothelial cells and for at least 7 days when cultured with either bovine or human endothelial cell-derived conditioned medium. The cocultured eosinophils became hypodense and generated about three times as much leukotriene C4 upon activation with calcium ionophore and killed about three times as many antibody-coated larvae of Schistosoma mansoni as freshly isolated normodense eosinophils. That these cells can be maintained in vitro by coculture with endothelial cells, and the surprising finding that the cocultured eosinophils have biochemical, cytotoxic, and density properties similar to those of eosinophils in patients with allergic and other disorders, will facilitate investigation of the regulation and role of these cells in health and disease. PMID- 3110955 TI - Chorea in systemic lupus erythematosus and "lupus-like" disease: association with antiphospholipid antibodies. AB - Twelve patients with chorea from a population of 500 patients with SLE and "lupus like" disease were reviewed. Clinical histories, including time relationships of chorea to the systemic illness and other neurologic manifestations, are reported. Chorea appeared early in the course of disease in most patients, but the development of cerebral infarctions or TIAs occurred subsequently in seven of nine patients demonstrating antiphospholipid antibodies. The relationship of chorea to the presence of these antibodies in nine of 12 patients and the therapeutic outcome are briefly discussed. PMID- 3110956 TI - Gold induced thrombocytopenia: 12 cases and a review of the literature. AB - Gold induced thrombocytopenia is immune mediated, with the production of platelet associated IgG leading to peripheral platelet destruction. An association with HLA-DR3 has been demonstrated. Corticosteroid therapy is effective in treatment, although other modes of therapy may be as efficacious. PMID- 3110957 TI - Nutritional factors in epidemic Kaposi's sarcoma. AB - The role of nutritional factors in the management of acquired immunodeficiency syndrome-related, or epidemic, Kaposi's sarcoma (EKS) is complex, since there are known interactions between malnutrition, immunodeficiency, and cancer. Malnutrition is a well-established cause of immune aberrations, which are seen in deficiencies of both protein and energy, as well as specific nutrients, particularly trace metals. Conversely, malnutrition is a common result of both cancer and immunodeficiency. Cancer patients without an obviously immunological pathogenesis frequently have malnutrition and cachexia, mainly as a result of a decreased dietary intake and poorly defined host-tumor interactions (commonly labeled "hypermetabolic"). Patients with primary immunodeficiency syndromes similarly experience a triad of diarrhea, malabsorption, and weight loss, which are responsible for the development of malnutrition. This triad is common in patients with AIDS, with or without the presence of Kaposi's sarcoma. The specific mechanisms of these interactions in EKS patients are largely unexplored; although some can be explained by the enteropathic effects of opportunistic infections, others can not. Some investigators have advocated careful nutritional evaluation of all AIDS patients, with vigorous nutritional support to be provided where assessment reveals suboptimal nutritional status. Specific nutrient deficiencies have been reported, of which selenium may be the most interesting; preliminary data indicate that it may be responsible for a malnutrition-related immunodepression seen with AIDS. Such supportive measures may significantly improve symptomatic relief, but there is as yet no evidence that they alter the course of the disease. PMID- 3110958 TI - Role of fibrinolysis in thrombotic thrombocytopenic purpura. PMID- 3110959 TI - [1st centenary of the patron saints of hospitals and the sick Camilo de Lellis and Jaao de Deus]. PMID- 3110960 TI - [Records]. PMID- 3110961 TI - [Mechanical ventilation]. PMID- 3110962 TI - [Humanitarian treatment of the patient]. PMID- 3110963 TI - [Trampling of rights in old age homes]. PMID- 3110964 TI - [Surgical treatment of obesity]. PMID- 3110965 TI - [Sexual hygiene]. PMID- 3110966 TI - [Syphilis and gonorrhea keep company]. PMID- 3110967 TI - [Hypertension in pregnancy. The heavy load of parturition and the puerperium]. PMID- 3110968 TI - Maintaining professional quality through innovation and changes in health care. PMID- 3110969 TI - The measurement of hospital efficiency. AB - The measurement of efficiency in the hospital sector is particularly difficult given that there is no universally recognised objective function. A generalised neo-classical approach is adopted in specifying a hospital objective function which acknowledges the importance of transaction costs and property right holdings in this sector. It is shown that such an approach may be used to distinguish between technical and allocative efficiency, thereby aiding interpretation of the stochastic element contained in production models. Quantification of allocative inefficiency is also undertaken. PMID- 3110970 TI - Diabetic ketoacidosis: effective low-cost treatment in a community hospital. AB - Diabetic ketoacidosis can be effectively and economically treated by using low dose intravenous insulin and 2 to 3 liters of isotonic saline at 500 ml/hr to replace extracellular fluids, followed by 2 to 4 L of 5% glucose in 0.45% saline with potassium chloride and/or potassium phosphate to replace intracellular fluids at 250 ml/hr. During the first six to nine hours serum glucose and potassium are measured every two to three hours, and bicarbonate, sodium, and chloride every four to six hours. Determination of arterial blood gas and serum ketone levels, electrocardiograms, and chest x-ray films are done only when indicated, and not routinely. Few patients need to be treated in an intensive care unit, and most can be discharged in three days. This protocol has been safe and effective without mortality in 250 consecutive patients. By eliminating unnecessary laboratory tests, costs have been greatly reduced without deterioration in results. PMID- 3110971 TI - Nosocomial infectious balanoposthitis in neutropenic patients. AB - We have reported balanoposthitis as a source of fever and bacteremia in two neutropenic uncircumcised patients. The etiologic organisms were Pseudomonas aeruginosa in one case and Providencia stuartii in the other. In one patient, the diagnosis was delayed by the presence of a condom catheter. This emphasizes the importance of personal hygiene in uncircumcised men about to undergo immunosuppressive therapy, and the need for judicious use of condom catheters in such patients. PMID- 3110972 TI - [Role of hypolactasia in the development of milk intolerance after various surgical procedures on the stomach]. PMID- 3110973 TI - [The unconjugated hyperbilirubinemia syndrome in chronic liver diseases]. PMID- 3110974 TI - [Efficacy of a program for the control of nosocomial infections: a real possibility for improving the quality of medical care]. PMID- 3110975 TI - [Reservoirs and vectors of Trypanosoma cruzi in the state of Oaxaca]. PMID- 3110976 TI - [The demographic impact of infant survival programs. Proposals for program strategy and policy]. PMID- 3110978 TI - [Lyme disease]. PMID- 3110977 TI - Molecular analysis of immunoglobulin expression in variants of murine B lymphoma, 70Z/3. AB - We have used a genetic approach to study the differentiation of B lymphocytes. Our model system is the induction of membrane immunoglobulin M-positive (mIgM+) cells in the murine B cell tumor, 70Z/3 by three extracellular mediators: lipopolysaccharide (LPS), supernatants from concanavalin A-stimulated rat spleen cells (CAS) and gamma interferon (IFN). The wild-type 70Z/3 cells synthesize constitutively the mu immunoglobulin heavy chain, but the kappa (kappa) light chain is expressed at extremely low levels. Treatment with these three inducers markedly increases kappa synthesis and allows the expression of IgM on the cell surface. We have selected variants which respond aberrantly to LPS and have analyzed their responses to the other inducers. We have analyzed mIgM expression, mu and kappa mRNA and protein levels. Our results show that the level of kappa mRNA is the most sensitive indicator of cellular response to an inducer. The independence of the variant phenotypes demonstrates that the pathways are not identical. PMID- 3110979 TI - Comparative costs of antibiotic regimens using multiple and single daily intravenous injections in surgical wards. PMID- 3110980 TI - The cost of preventive medicine. PMID- 3110981 TI - A comparative study of misoprostol and ranitidine in the healing of duodenal ulcers. A double-blind controlled trial. AB - This study was undertaken to evaluate the safety and therapeutic efficacy of the prostaglandin E1 analogue, misoprostol, when compared with ranitidine in the healing of duodenal ulcers. Sixty patients with endoscopically proven duodenal ulcers participated in a double-blind controlled randomised trial comparing misoprostol 400 microgram and ranitidine 150 mg, both given twice daily orally for up to 8 weeks. Patient characteristics at entry into the trial were similar in the two treatment groups, except that there were 6 women in the ranitidine treated group and none in the misoprostol-treated group. Ulcers were 0.3 - 2.0 cm in length. Healing was determined by endoscopy at 4 weeks; if ulcers were not healed, endoscopy was repeated at 8 weeks. All patients were given antacid tablets to be used as needed for pain up to a maximum of 8 tablets per day. Healing rates at 4 weeks for a total of 58 evaluate patients in the two treatment groups were: misoprostol (15/29; 51.7%) and ranitidine (20/29; 69.0%). Healing rates at 8 weeks for a total of 55 evaluable patients in the two treatment groups were: misoprostol (21/27; 77.8%) and ranitidine (24/28; 85.7%). The healing rate for misoprostol did not differ significantly from that for ranitidine at both the 4-week (P = 0.28) and the 8-week assessment (P = 0.68). Diarrhoea was the most common side-effect but was usually mild. It occurred in 11 patients on misoprostol and 1 patient on ranitidine. These results indicate that misoprostol 400 micrograms was taken twice daily orally for up to 8 weeks is effective and safe for the treatment of duodenal ulcer. PMID- 3110982 TI - Surviving DRG's: New Jersey's social work experience with prospective payments. AB - This is a report of a study which examined the impact of New Jersey's four-year experience with all-payer DRG's upon 82 hospital social work departments as these were reported by their directors. Although DRG's have made discharge planning, and thus social work, central to hospitals' financial health, departments have faced increased caseloads and some refocus of staff deployment, not always with compensatory increases in staff. Strategies to survive the cost-containment policies and other implications are noted. PMID- 3110983 TI - [Preoperative radiochemotherapy in advanced oral and oropharyngeal carcinoma]. AB - In a prospective study, 16 patients with advanced carcinoma of oral cavity and oropharynx were submitted to a combined preoperative radio-chemotherapy. The radiosensitizers mitomycin and 5 fluorouracil were given simultaneously with the beginning of radio-therapy. The primary tumor as well as the lymph node regions were exposed to a total dose of 50 Gy administered over five weeks. Eight out of 16 pretreated patients had a complete histological remission, 4/16 a partial remission, and 4/16 showed a tumor reduction of less than 50%. A progression was found in no case. The treatment of lymph node metastases had a slightly poorer effect: CR 7/16, PR 3/16, NC 5/16, PD 0. Therapy effect and side effects as well as the effect on late results of simultaneous radio-chemotherapy are discussed. PMID- 3110984 TI - [Radiotherapy of choroid metastases in breast carcinoma]. AB - From 1975 to 1984, thirteen patients were submitted to radiotherapy for choroid metastases of mammary carcinoma. Bilateral manifestation was found in three cases, thus sixteen eyes have been treated. All irradiations were performed with high voltage equipment. The posterior section of the eye was irradiated with 25 to 50 Gy over 2.5 to 5 weeks. Complete regression was achieved in nine out of sixteen cases, five patients showed an improvement of at least 50%, no considerable effect was found in two cases. The survival is 4 to 48 months (median survival 20 months) from the beginning of radiotherapy. Radiotherapy is a quick, efficient, and sparing treatment in choroid metastases. If applied in due time, it can prevent a visual disorder or amaurosis, thus improving the patients' quality of life. PMID- 3110985 TI - [Field-integrated dose modification. 1: Clinical significance of the procedure]. AB - A method is derived from a previously published compensator-integrated modification proceeding which maintains the principle of a field-integrated dose modification without needing CT input data. Three typical clinical examples are presented in order to describe this considerably simplified technique thus suited for everyday practice. The authors discuss the interesting radiobiological aspects involved. PMID- 3110986 TI - [World congress on ADP. From data processing to knowledge development]. PMID- 3110987 TI - [Denmark in 10 years: an entire hospital filled with AIDS patients?]. PMID- 3110988 TI - [We must support children on long-term steroid therapy]. PMID- 3110989 TI - [Corrective effect of nitrates and calcium antagonists on hemodynamics and ventilation in chronic bronchitis patients with a syndrome of pulmonary hypertension]. PMID- 3110990 TI - [Pulmonary function of patients with bird-breeders' exogenous allergic alveolitis]. AB - A total of 59 bird fanciers suffering from alveolitis were examined, of them 23 with alveolitis of bronchitis type, 24 with alveolitis of pneumonic type and 11 alveolitis of fibrosing type. In all 3 variants of a course of alveolitis the obstructive syndrome was the main sign of functional disturbances. Intrapulmonary gas exchange disturbances slightly expressed in alveolitis of bronchitis type and pneumonic type, acquired greater importance in fibrosing alveolitis. The absence of restrictive changes in the patients could result from weakly expressed fibrosing of the pulmonary tissue, its combination with emphysematous-dystrophic changes as well as with lung hyperinflation as a result of disturbances in bronchial permeability. PMID- 3110991 TI - [Detection of pulmonary tuberculosis in adolescents in institutions of the general medical network and efficacy of its treatment]. AB - Altogether 100 adolescents with TB detected on referral to general medical institutions were followed up. 30 patients with a clear-cut TB clinicoroentgenological pictures were referred to special hospitals. The rest 70 adolescents were followed up in general outpatients departments. The chief method of prehospital diagnosis verification was inefficacy of previous antiinflammatory therapy. 51 patients were not examined for tuberculosis (tuberculin test, chest x ray, sputum investigation for tubercle bacilli, phthisiologist's consultation, etc.). Clinical evaluation showed that 47% had had previous contacts with tuberculosis patients, 33% demonstrated hyperergic sensitivity to tuberculin, in 21% the disease coincided with intensification of tuberculin reactions, 55% isolated tubercle bacilli. Initiated antituberculosis therapy alleviated the disease course in most of the patients. However, late diagnosis resulted in the formation of noticeable residual changes in a considerable proportion of patients. The results obtained indicate the necessity of close contacts between antituberculosis service and general health service to improve the effectiveness of adolescents therapy. PMID- 3110992 TI - Teratogenicity and developmental toxicity of valproic acid in rats. AB - The teratogenicity and developmental toxicity of valproic acid (VPA) was investigated in Sprague-Dawley CD rats at doses of 0, 150, 200, 300, 400, and 600 mg/kg administered by gavage on days 7-18 of gestation. The VPA-600 dose was maternally toxic, causing death in two of four dams. This dose produced 100% embryonic resorption. The VPA-400 dose was maternally toxic in as much as maternal weight gain was reduced, but no deaths occurred. At this dose five of fifteen litters were completely resorbed, and 52% of all embryos were resorbed. Among survivors, 49% were malformed (68% having skeletal defects and 41% visceral defects). Fetal weight was reduced by 43% in this group. Most of the defects were ectrodactyly, hydronephrosis, cardiovascular defects, hypoplastic bladder, rib and vertebral defects, and other defects of the limbs and tail. The VPA-300 dose (nine litters) produced fewer defects, larger fetuses, and no increase in resorptions. The defects at this dose were primarily cariovascular, rib, and vertebral. The VPA-200 dose (12 litters) produced no reduction in fetal weight, no increase in resorptions, and few defects. The defects noted were hydronephrosis, cardiovascular abnormalities, and rib defects, primarily wavy ribs. Additional litters were prepared using doses of 150 and 200 mg/kg and were allowed to deliver and grow until 70 days. These doses produced no reduction in maternal weight gain, no reduction in litter size, birth weight, or sex ratio of the offspring. These doses produced no reduction in offspring weight to day 70, no increase in mortality, and only rare cases (two offspring of each dose) of tail defects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110993 TI - A selective depression of tissue plasminogen activator (t-PA) activity in euglobulins characterises a risk group among survivors of acute myocardial infarction. AB - Among 29 patients recovering from a first-time acute myocardial infarction (AMI) 9 patients suffered reinfarction during a four year follow-up period. The 9 reinfarction patients were found to belong to a subgroup of 17 patients with a selective depression to near zero of euglobulin t-PA activity. None of the group of 12 patients with marked t-PA activity suffered a relapse. Euglobulin fibrinolytic activity as usually assayed did not distinguish between groups with or without relapse. PMID- 3110994 TI - Increased plasminogen activator inhibition levels in malignancy. AB - Plasminogen activator(PA)-tissue and urokinase type-and PA-inhibition in plasma were investigated in 52 consecutive cancer patients with a variety of tumors. At first patients were analyzed as one group. Secondly patients were subdivided into two groups, one with (n = 42) and one without (n = 10) metastasis. Our results show that tissue-type-PA antigen (t-PA-antigen) and PA-inhibition were both significantly increased irrespective of the presence or absence of tumor metastasis (p less than 0.001 compared to age matched healthy controls. In the group without metastasis a significantly decreased level of t-PA activity was found (p less than 0.001) but in the group with metastasis t-PA activity was normal. These data seem to reject the hypothesis that decreased plasma fibrinolytic activity is one of the prerequisites for tumor metastasis. PMID- 3110995 TI - Detection and quantitative evaluation of lupus circulating anticoagulant activity. AB - Sixty-six SLE patients were studied for the presence of lupus type circulating anticoagulant. Forty-nine percent of them showed activity of this anticoagulant. The sensitivity of various coagulation tests was compared. Recalcification time was found to be the most sensitive screening test and the kaolin clotting time mixture test, the best for determining the presence of the anticoagulant. Tissue thromboplastin inhibition test detected only half of the patients in whom the anticoagulant was found by recalcification time and kaolin clotting time mixture test. APTT, using 2 different reagents, resulted in 73% and 52% false negatives. A numerical index for determining the presence of the anticoagulant and its quantitative evaluation is suggested. The association between thromboembolic events, recurrent abortions and the different coagulation tests is shown. PMID- 3110996 TI - Effect of the polyamine-spermine on agonist-induced human platelet activation- specific inhibition of "aggregation-independent" events induced by thrombin, but not by collagen, thromboxane mimetic, phorbol ester or calcium ionophore. AB - Spermine, a naturally occurring polyamine, has previously been described as an inhibitor of purified phospholipase C and protein kinase C in cell-free systems. The present study examines the effect of spermine on platelet aggregation, dense granule secretion and thromboxane (Tx) B2 synthesis induced by a variety of agonists, which cause the activation of one or both enzymes to different extents. These studies revealed that, while spermine (10 mM) inhibited platelet aggregation in response to all the agonists examined, [14C]-5-hydroxytryptamine (5HT) release and TxB2 synthesis induced by thrombin (0.2 U/ml) and collagen (10 40 micrograms/ml) alone, were inhibited by spermine, the percentage inhibition being greater than 90% for both responses with thrombin, 30% for 5HT release and 80% for TxB2 synthesis with collagen. The inhibition of collagen-induced [14C] 5HT secretion by spermine was due entirely to the inhibition of aggregation dependent TxA2 synthesis as addition of a sub-threshold concentration of U46619, which induced no secretion on its own, totally restored collagen-induced [14C] 5HT secretion to the levels seen in the absence of spermine. Moreover, collagen induced TxB2 formation in unstirred platelets, which occurred independently of aggregation was not significantly affected by spermine (10 mM). However, the inhibition of maximal thrombin-induced [14C]-5HT secretion and TxB2 synthesis, which are both aggregation-independent phenomena, could be attributed to the inhibition of thrombin-induced diacylglycerol formation and intracellular calcium mobilization, which were both inhibited by 80% in the presence of spermine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3110997 TI - A sensitive solid-phase immunosorbent assay for tissue-type plasminogen activator activity in plasma using trinitrobenzoylated poly-D-lysine as a stimulator for plasminogen activation. AB - A sensitive, specific and precise immunosorbent assay for tissue-type plasminogen activator (t-PA) activity in plasma was developed. It measured the single-chain and the two-chain forms of t-PA with equal sensitivity. The assay involved (I) coating of wells in microtiter plates with a monoclonal antibody directed towards an epitope on t-PA apart from the catalytic active site, (II) binding of t-PA to the solid-phase antibody, (III) activation of plasminogen by antibody-bound t-PA in the presence of a new potent stimulator, trinitrobenzyl alkylated poly-D lysine (TNB-poly-D-lysine) and measurement of plasmin activity with D-Val-Leu-Lys pNA. Plasma samples were acid-treated and diluted 80 times in order to minimize the inhibitory effect of plasma on the assays. The assay could be performed within one working day with precoated microtiter plates. The sensitivity of the assay for t-PA in plasma was 1 pM (approximately 70 ng/l). The recoveries of single-chain and two-chain t-PA added to plasma was 97-104%. The intraassay coefficient of variation was 3.4-5.1% and the interassay coefficient of variation was 7.8-18%. Resting values of t-PA in plasma for 42 healthy subjects ranged between 0 and 30 pM (median: 4.1 pM). The values after 10 min venous occlusion ranged between 1.2 and 520 pM (median: 100 pM). The t-PA concentrations determined by the immunosorbent assay correlated well with euglobulin clot lysis time measurements (r = 0.940). PMID- 3110998 TI - Acquired factor VIII inhibitor associated with multiple sclerosis, successfully treated with porcine factor VIII. PMID- 3110999 TI - Maternal lupus anticoagulant and fatal neonatal thrombosis. PMID- 3111000 TI - Aspirin decreases fibrinolytic potential during venous occlusion, but not during acute physical activity. AB - It has previously been observed that aspirin diminishes the increase in blood fibrinolytic activity during arm venous occlusion. We studied the duration of this inhibitory effect on fibrinolytic response during 20 minutes arm venous occlusion and its effect on fibrinolytic response during acute physical activity (standardized stress testing on treadmill) in 10 healthy male volunteers. Fibrinolytic activity was measured with euglobulin clot lysis time and fibrin plates before and after both stimuli, and t-PA release estimated as the difference between post- and prestimulation values (fibrinolytic potential: FP). Venous occlusions were performed before aspirin ingestion and then on the first, second, third, and fourth to eighth day after aspirin. Stress testing was carried out on two successive days before and after aspirin ingestion. Aspirin did not affect basal fibrinolytic activity, but significantly decreased FP during occlusion. This effect was sustained for the whole period of observation. To the contrary, aspirin did not influence FP during acute physical activity. The different effect of aspirin on fibrinolytic response during venous occlusion and physical activity suggested that different mechanisms were involved in t-PA release during both stimuli. PMID- 3111002 TI - Binding of tissue plasminogen activator to human umbilical vein endothelial cells. AB - Binding of purified recombinant human tissue plasminogen activator to cultures of human umbilical vein endothelial cells (HUVEC) was studied in vitro. 125I-tPA was shown to bind to HUVEC in a specific, saturable, and dissociable manner. Scatchard analysis revealed a low affinity binding site with Keq = 4.2 X 10(6) M 1 and 1.2 X 10(7) sites per cell. Binding of tPA was inhibited by L-lysine, e aminocaproic acid, and D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone but not by carbohydrates including mannose, galactose, N-acetyl glucosamine and N acetyl galactosamine. Neat human plasma abrogates but does not totally inhibit binding of tPA to HUVEC. These results may indicate a role for endothelial cells in the removal of tPA from the circulation in vivo. PMID- 3111001 TI - Measurement of tissue plasminogen activator in plasma. A comparison of 3 methods and description of a new improved technique. AB - Three methods for measurement of tissue plasminogen activator (t-PA) activity in plasma were compared with regard to linearity, precision and clinical applicability. Based on this comparison a new improved technique is described. The 3 methods differed in the way the influence of inhibitors in plasma was eliminated. In method A t-PA was measured in acidified plasma, in method B in euglobulin precipitate and in method C after adsorption of plasma on lysine Sepharose. After addition of 15 IU/ml of t-PA to normal plasma the recovery with method A was 17.4 +/- 2.4 IU/ml, with method B 11.4 +/- 0.5 IU/ml and with method C 9.8 +/- 0.9 IU/ml. When tested on venous stasis plasma from 10 patients the 3 methods correlated well with a correlation coefficient of r = 0.97 - 0.99. Significantly higher values were found in acidified plasma (method A) as compared to the other methods. From this evaluation a method for determination of t-PA activity using acidification and internal standard to abolish the influence of inhibitors and poly-D-lysine as a stimulator was selected. The recovery with this method was 103.4 +/- 8.5% independent of PA inhibitor content in the plasma. PMID- 3111003 TI - Altered intraplatelet arachidonic acid metabolism during the acute state of unstable angina. AB - Thromboxane A2 (TxA2) generation and 1-14C arachidonic acid (AA) metabolism by platelets (stimulated with thrombin) were studied in vitro in 16 patients with unstable angina both during the acute and chronic inactive phase of the angina. Eight patients with stable effort angina and 21 controls were also investigated. In acute unstable angina 1-14C AA metabolism was significantly increased through cyclooxygenase pathway resulting in a higher selective TxA2 generation than in stable effort angina and in controls (p less than 0.01). No differences were found between patients with stable effort angina and controls. The alterations in AA metabolism were no longer found when patients reverted to the inactive phase of angina. TxA2 generation by platelets was independent of the number of the daily ischemic attacks (r = 0.17, ns) in patients with unstable angina. Present results indicate that an altered intraplatelet AA metabolism leading to the increased TxA2 synthesis occurs simultaneously with the conversion of angina from the chronic to the acute phase. PMID- 3111004 TI - Ouabain affects platelet reactivity as measured in vitro. AB - Ouabain, a digitalis glycoside and an inhibitor of the Mg2+-dependent Na+-K+ ATPase, was used to probe the role of intracellular Na+ levels in the regulation of platelet reactivity. Platelets preincubated with 10 to 150 microM ouabain exhibited a potentiated aggregation response to collagen (14.4 to 180 micrograms/mL), ADP (4 to 12 microM) and thrombin (0.03 to 0.10 unit/mL). Ouabain markedly decreased the time interval between addition of collagen and the onset of shape change. At submaximal concentrations of collagen, thrombin and ADP, preincubation with ouabain increased the rate and amplitude of the aggregation response. Irreversible aggregation was achieved in ouabain-treated platelets by using concentrations of ADP which induced only reversible aggregation in the absence of ouabain. In addition, chelation of extracellular calcium with EGTA or EDTA (2 mM) failed to block reactivity to collagen, ADP or thrombin in ouabain treated platelets. These results suggest that ouabain induces a "preactivation state" in platelets, perhaps via modulation of intracellular Na+ levels. PMID- 3111005 TI - The influence of anticoagulant on the in vitro level and stability of factor VIII procoagulant activity. PMID- 3111006 TI - [Development of tolerance to glyceryl trinitrate and other nitrates]. PMID- 3111007 TI - [Lupus anticoagulant. Coagulation inhibitor associated with thrombosis tendency]. PMID- 3111008 TI - [Current problems in the prevention of infection during transportation of samples]. PMID- 3111009 TI - [Clinical experiences with a hormone-releasing intrauterine device]. PMID- 3111010 TI - Measuring nursing costs with patient acuity data. PMID- 3111011 TI - Utilizing cost accounting information for budgeting. PMID- 3111012 TI - Measuring costs: product line accounting versus ratio of cost to charges. PMID- 3111014 TI - The effect of 3,4,3',4'-tetrachlorobiphenyl on plasma retinol and hepatic retinyl palmitate hydrolase activity in female Sprague-Dawley rats. AB - The Effect of 3,4,3',4'-Tetrachlorobiphenyl on Plasma Retinol and Hepatic Retinyl Palmitate Hydrolase Activity in Female Sprague-Dawley Rats. Powers, R.H., Gilbert, L.C., and Aust, S.D. (1987). Toxicol Appl. Pharmacol. 89, 370-377. A single ip dose of 1, 5, or 15 mg/kg 3,4,3',4'-tetrachlorobiphenyl (TCB) caused a dose-dependent depression of plasma retinol levels 24 hr after treatment of female Sprague-Dawley rats. The loss of plasma retinol appeared to be a function of depressed levels of the retinol-retinol-binding protein (RBP)-transthyretin ternary complex. No free retinol-RBP was observed in plasma from treated animals. Hepatic retinyl palmitate hydrolase (RPH) activity was also depressed and highly and positively correlated to the plasma retinol levels. TCB was determined to be a noncompetitive inhibitor of partially purified RPH with a KI of 91 microM. Incubation of TCB with liver microsomes and NADPH decreased the inhibition of RPH. Doses of either 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) or 3,4,5,3',4',5' HCB equimolar to the 15 mg/kg TCB dose failed to cause a similar depression of plasma retinol in treated female rats. We conclude that, unlike other polychlorinated biphenyl congeners, TCB causes a depression of plasma retinol by inhibition of hepatic RPH. PMID- 3111013 TI - Changes in thyroid hormones and thyroxine glucuronidation in hamsters compared with rats following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - In rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, serum thyroxine (T4) is depressed. Since hamsters are relatively insensitive to TCDD-induced lethality, the effects of TCDD on several parameters of thyroid status were measured in hamsters as a comparison with the more sensitive rat. At 7 days after ip injection of TCDD, there was a dose-dependent increase in serum 3,5,3'-triiodothyronine (T3) and T4 in hamsters to a maximum level 200% of control; the ED50 was approximately 10 micrograms/kg. Hamsters receiving 100 micrograms/kg lost up to 4% of their body weight but began to recover after about 3 weeks. Serum T4 in these animals was elevated compared to pair-fed and ad libitum controls throughout the 53-day experiment, although it also began to recover after Day 21. This was in direct contrast to the marked reduction of T4 in rats exposed to lower doses of TCDD. T3 was significantly higher in TCDD-treated hamsters than in pair-fed controls on Days 2-7, and TSH was also elevated on Days 2-21. Reverse T3, like T4, was increased by TCDD in hamsters whereas it was decreased in rats. Hepatic microsomal UDP glucuronosyltransferase (GT) activity was measured using T4 as substrate (T4-GT). On a whole liver basis, T4-GT was induced by TCDD by the same proportion in both rats and hamsters (170-180% of controls) although absolute activities in rats were 3- to 4-fold higher than in hamsters. This similarity in T4-GT inducibility by TCDD suggests that there are likely mechanisms in addition to T4-GT induction which account for the species-specific alterations in T4. Thus, while the response of thyroid hormones to TCDD differed qualitatively, effective doses in hamsters were higher than in rats, suggesting that these changes, although secondary, may correlate more directly with toxicity than does enzyme induction (whose ED50s are similar in both species). An understanding of the mechanism of this species difference may be helpful in unravelling the primary mechanisms of TCDD toxicity. PMID- 3111015 TI - Suppression of bone marrow stromal cell function by benzene and hydroquinone is ameliorated by indomethacin. AB - Administration of benzene to mice will inhibit bone marrow stromal cell-supported hemopoiesis in culture. Hydroquinone, a major metabolite of benzene, will cause a similar inhibition of stromal cell function in vitro. Stromal cells produce both an inducer (colony-stimulating factor) and an inhibitor (prostaglandin E2; PGE2) of hemopoiesis. This research was conducted to determine if prostaglandin synthesis is involved in the suppression of stromal cell function by benzene and hydroquinone. Male B6C3F1 mice were administered benzene (100 mg/kg), indomethacin (1 mg/kg), or benzene plus indomethacin twice a day for 4 consecutive days. On Day 5 bone marrow cells were removed to determine the effect of treatment. In a second series of experiments mouse bone marrow stromal cells in culture were treated with hydroquinone (10(-7) to 10(-4) M), indomethacin (10( 6) M), or a combination of hydroquinone plus indomethacin. Stromal cell function was based on the ability of the treated stromal cells to support granulocyte/monocyte colony development in coculture. The results demonstrated that preadministration of indomethacin in vivo ameliorated benzene-induced inhibition of bone marrow stromal cell function. In vitro, indomethacin ameliorated hydroquinone toxicity to stromal cell function. Benzene administration in vivo induced elevated PGE2 in bone marrow samples which were prevented by preadministration of indomethacin. However, hydroquinone in vitro did not induce a consistent increase in PGE2 levels. These results suggested that toxicity to stromal cells was not due solely to increased prostaglandin synthetase activity. PMID- 3111016 TI - Structure-activity relationships for mono alkylated or halogenated phenols. AB - The quantitative structure-activity relationships between toxicity (log BR), monitored as cell population growth, and two molecular descriptors, the log 1 octanol/water partition coefficient (log Kow) and the Hammett sigma constant (sigma) or the ionization parameter (pKa) for a series of 17 ortho-, meta- and para-substituted alkylated or halogenated phenols have been examined. The equation: log BR = 0.7998 (log Kow) + 1.2447 (sigma) - 1.5538; r2 = 0.897 s = 0.170 has been found to be an excellent planar model for these chemicals. This model uses the para-position sigma constant as the estimator of ortho-position electronic effects. A similar equation: log BR = 0.7845 (log Kow) - 0.3702 (pKa) + 2.1144; r2 = 0.860 s = 0.199 has been developed using pKa in place of sigma. PMID- 3111018 TI - [The role of an advanced technical school in dental technology and the masters examination as an indication of future accomplishments]. PMID- 3111017 TI - Cerebral venous thrombosis with lupus anticoagulants. Report of two cases. AB - Lupus anticoagulants are circulating autoantibodies, primarily directed against phospholipids, that prolong the partial thromboplastin time. They have been previously associated with systemic arterial and venous thrombosis and arterial stroke, but not with cerebral venous thrombosis. We describe 2 young patients with cerebral venous thrombosis documented by intravenous digital subtraction angiography in whom a lupus anticoagulant was demonstrated. Both patients improved with corticosteroid and anticoagulant therapy. PMID- 3111019 TI - [Materials specific preparation of dental materials in a modern dental practice. Guidelines for the dental hygienist]. PMID- 3111020 TI - Patient education--implications for nursing. PMID- 3111021 TI - Genetic and other constraints on resistance to infection with gastrointestinal nematodes. AB - Infections with gastrointestinal (GI) nematodes are among the most prevalent infections of man. Not only are they common and widespread in populations throughout the world, but they are frequently chronic and occur repeatedly throughout the lifetime of an individual. It is now well established that such parasites can be highly immunogenic and that their environment, the gastrointestinal tract, is well equipped to mount potent immune and inflammatory responses. The abundance and long-term survival of GI nematodes therefore present a paradox. This review takes the standpoint that man as a species has the capacity to produce effective and protective responses against GI infections, but that this capacity is subject to a number of powerful constraints, arising from parasite evasion, depression of response capacity and deficiency in response capacity. These constraints are discussed in the light of evidence drawn from experimental studies with animal models. PMID- 3111022 TI - Influence of aflatoxin on nutrition and malaria in mice. PMID- 3111023 TI - Does ancylostomiasis favour the intensity of Schistosoma mansoni infection? PMID- 3111024 TI - Antibody to Japanese strain of haemorrhagic fever with renal syndrome (HFRS) virus in Nigerian sera. PMID- 3111025 TI - Transmission of urinary schistosomiasis in man-made habitats in The Gambia. PMID- 3111026 TI - Oltipraz: administration with food increases its anti-schistosomal activity. AB - In a previous study it was demonstrated that the concentration of oltipraz in the plasma of human volunteers was significantly elevated when administered with food. In this study we attempted to determine if this food-induced increase was associated with an increase in the drug's anti-schistosomal activity. The drug was administered with and without food to two groups of patients infected with Schistosoma mansoni. The concentration of oltipraz in the plasma of these patients was measured at varying intervals after dosing. Results indicate that the food-induced increase in the bioavailability of oltipraz in patients with S. mansoni produces a significant increase in the drug's anti-schistosomal activity. PMID- 3111027 TI - Blood glutathione in severe malnutrition in childhood. AB - The blood glutathione (GSH) concentration was measured in 25 severely malnourished children and compared with a group of normal adults. In children with marasmus GSH (3.3 +/- 0.7 mg/gHb) was not different from normal (2.9 +/- 0.4 mg/gHb). However there was a highly significant decrease in all forms of oedematous malnutrition, kwashiorkor (1.5 +/- 0.4 mg/gHb) and marasmic kwashiorkor (1.7 +/- 0.7 mg/gHb). There was no relationship between wasting or stunting and blood GSH. PMID- 3111028 TI - The incidence of squamous and transitional cell carcinomas of the urinary bladder in northern Tanzania in areas of high and low levels of endemic Schistosoma haematobium infection. AB - Squamous cell carcinoma is the commonest type of bladder malignancy in most areas of northern Tanzania. Of 172 cases of bladder cancer recorded in 9 years, 72% were squamous cell carcinomas. Of these, 46% had Schistosoma haematobium eggs in sections taken from tumour tissue. The geographical distribution of this tumour closely corresponded to the prevalence of S. haematobium infection. The Mt Kilimanjaro area is free of schistosomiasis and virtually lacks squamous cell carcinoma. Although transitional cell carcinoma is rare in all regions of northern Tanzania, the relative frequency of bladder cancer in the Mt Kilimanjaro area was only one-third of that seen in other regions; population-based incidence rates were also very low in this area. PMID- 3111030 TI - Immune responses and immunoregulation in relation to human schistosomiasis in Egypt. III. Immunity and longitudinal studies of in vitro responsiveness after treatment. AB - Immune responsiveness of schistosomiasis patients was assayed longitudinally, before and for two years after chemotherapeutic treatment with praziquantel, by in vitro peripheral blood mononuclear cell (PBMN) proliferation upon exposure to phytohaemagglutinin (PHA), or soluble schistosomal antigenic preparations from eggs (SEA), adult worms (SWAP) or cercariae (CAP). Parallel faecal and urine examinations documented the infection status of the patients during this time. Treatment resulted in substantially increased responsiveness to the schistosome derived materials but not to PHA or C. albicans extract. The responses to SEA, SWAP, and CAP often remained elevated for one to two years after treatment. However, those patients who became reinfected had significantly lower PBMN responses to SEA or CAP at the time of the last blastogenesis assay before the observation that they were again stool-positive for Schistosoma mansoni eggs. No other demonstrable differences (such as age, sex, household location, pre treatment intensities of infection or occupation) were observed between those who remained uninfected for at least two years (resistant?) and those who became reinfected during this time (susceptible?). PMID- 3111031 TI - How Schistosoma mansoni eggs reach natural waterbodies. PMID- 3111029 TI - Aflatoxins and kwashiorkor: clinical studies in Sudanese children. AB - Aflatoxin analysis of blood and urine by high performance liquid chromatography in 584 Sudanese children is reported. The results in 404 malnourished children comprising 141 kwashiorkor, 111 marasmic kwashiorkor and 152 with marasmus are compared with 180 age-matched controls and correlated with clinical findings. The aflatoxin detection rate and mean concentration were higher in serum of children with kwashiorkor than the other groups. The difference between the detection rate in kwashiorkor and controls was significant (p less than 0.05). The aflatoxin detection rate in urine was highest in the marasmic kwashiorkor group and the mean concentration was higher in the marasmic kwashiorkor and marasmic groups than in the kwashiorkor and control groups. There were important differences in the detection of certain aflatoxins between the groups. Aflatoxicol was detected in the sera of 16 (11.6%) kwashiorkor, in six (6.1%) marasmic kwashiorkor, but in none of the controls and only once in marasmus. These differences are highly significant (p less than 0.0001). The ratio of AFB1 to AFM1 was higher in the sera and urines of kwashiorkors than in controls, suggesting that the normal transformation of AFB1 to AFM1 may be impaired in kwashiorkor with consequent increase in transformation of AFB1 to aflatoxicol. The study therefore provides evidence of differences in the metabolism of aflatoxins in children with kwashiorkor compared with children with other forms of malnutrition and normally nourished children and confirms the association between aflatoxins and kwashiorkor contained in a preliminary report on this work. PMID- 3111032 TI - Evaluation of the interaction of leucocytes from Chagas disease patients with trypomastigotes of Trypanosoma cruzi. AB - We developed a method to asses the infectivity of Trypanosoma cruzi trypomastigotes for cultured Vero cells, after incubation under different conditions with human leucocyte populations. Total leucocytes, polymorphonuclear (PMN) and mononuclear (MN) cells, from either infected (INF) or cardiomyopathic (CDM) Chagas patients were tested in the presence or absence of autologous serum. Both patient groups had positive complement fixation tests (CFT) for T. cruzi and these were compared with a group of normal controls with negative CFT. Serum alone was found to cause reductions in the infectivity of the trypomastigotes, particularly in the case of CDM. However, in the control and INF groups, a significantly greater effect was observed with combinations of leucocytes and serum. The inhibition caused by cells plus serum was significantly greater in INF and CDM patients than in normal controls. In addition, we evaluated the penetration of trypomastigotes into the different types of leucocytes and found a significantly greater penetration of INF leucocytes at 15 min, compared to the controls, in the presence of both autologous and homologous normal serum. However, after 60 min of incubation the differences were not statistically significant. PMID- 3111033 TI - Density-dependent fecundity in Schistosoma mansoni infections in man: a reply. PMID- 3111034 TI - Could Crimea-Congo haemorrhagic fever be a biohazard in the Central African Republic? PMID- 3111035 TI - Hemagglutination enhancement by bovine serum albumin is affected by octanoate, Reactive Blue 2 (Cibacron Blue), and polymer. AB - An AutoAnalyzer system was used to study factors that influence the albumin enhancement of agglutination of Rh(D)-positive red cells by IgG anti-D. An albumin consisting of trimer and higher oligomer was more efficient than a preparation composed mainly of monomer and dimer. Modification of the hemagglutination-enhancing property of albumin was obtained by the addition of ligands (octanoate [caprylate] and Reactive Blue 2 [Cibacron Blue]). Irrespective of the polymer content, neither ligand alone had any effect on low-fatty-acid albumins. However, when mixtures of octanoate and Cibacron Blue were added to the same albumins, hemagglutination was initially increased, and then diminished with increasing concentrations of ligands. The enhancing property of high-fatty-acid, nonpolymerized albumin was markedly reduced by the addition of octanoate or Cibacron Blue. On the other hand, only Cibacron Blue could produce the same inhibitory effect on a polymerized albumin with high fatty acid content. The implication is that the total free fatty acids bound and polymer content are two independent variables that can affect the performance of an albumin as a hemagglutination enhancer. PMID- 3111036 TI - Fibrinogen content of low-volume cryoprecipitate. AB - Single-donor cryoprecipitate is the most convenient and reliable source of fibrinogen. A change by the regional Red Cross Blood Service to the production of low-volume cryoprecipitate led the authors to reexamine the fibrinogen content of cryoprecipitate units. The average fibrinogen content of individual low-volume (4 ml) units (n = 23) was 101 +/- 48 mg; in the 10-unit pools (n = 9 pools), content was 89 +/- 13 mg. Both measurements were considerably lower than previously published. By contrast, the mean fibrinogen content of regular-volume (15 ml) cryoprecipitate units (n = 8) was 142 +/- 50 mg. The fibrinogen was stable for at least 4 hours after thawing, and it survived refreezing and thawing. PMID- 3111037 TI - Clinical and immunological restoration in patients with AIDS after marrow transplantation, using lymphocyte transfusions from the marrow donor. AB - The diagnosis of transfusion-associated acquired immunodeficiency syndrome (AIDS) was made in 2 patients who developed delayed opportunistic infections and severe cytopenias--56 months for the former (patient 1) and 22 months for the latter, (patient 2) following bone marrow transplantation (BMT) for aplastic anemia. In the third case, grafting for acute leukemia (patient 3) (HIV) infection was probably responsible for the failure of hematological and immunological reconstitution 8 months after allogeneic BMT. Each patient received 6 lymphocyte transfusions from the marrow donor for 3 weeks, combined with a 3-month course of low-dose recombinant alpha interferon. This treatment was followed by recombinant gamma interferon for 3 months. We showed that these 3 patients could resume a normal life for 9 months, at least, and that hematological restoration was observed. Our treatment succeeded in correcting the defect of proliferative response to Candida and the impairment of gamma interferon generation for 4 months in one patient and for more than 12 months in the other two recipients. Nevertheless T4 lymphocyte levels increased only slightly and HIV can still be isolated from the patients' blood. At the time of writing, patients 1 and 3 remain in good health with a partial immunological restoration while patient 2 has died of neurological impairment 2 years after the AIDS diagnosis. Although we cannot generalize this successful therapeutic approach to all patients with AIDS, the results may provide an interesting model of the potential effect of lymphocyte transfusions and the role of interferon therapy. PMID- 3111038 TI - (Nva2)-cyclosporine--less potent than cyclosporine A in rats with lung and heart transplants. AB - The ability of a new cyclosporine (Cs) derivative, (Nva2)-Cs (CsG), to suppress rejection of lung and heart allografts in rats was determined and compared with that of CsA. Left lungs were transplanted orthotopically; hearts were transplanted heterotopically into the abdomen. (Nva2)-Cs was used in three experimental protocols: (1) single or three (Nva2)-Cs injections given to lung transplanted rats, (2) daily oral (Nva2)-Cs treatment at different doses compared with similar CsA treatments in heart allografted rats, and (3) An 11-day (Nva2) Cs treatment starting at increasing intervals after transplantation of hearts. (Nva2)-Cs was found to be immunosuppressive, and effective even when the treatment started as late as four days after transplantation. However, (Nva2)-Cs was less effective than CsA in suppressing rejection of lung and heart allografts at low doses. Because (Nva2)-Cs is possibly not nephrotoxic, it might be a useful drug if used in higher doses than CsA or in combination with other immunosuppressive agents. PMID- 3111039 TI - Survival of cryopreserved isolated adult human pancreatic islets of Langerhans. AB - Human islets of Langerhans were isolated from the pancreata of 13 adult organ donors, cultured for 24 h, cryopreserved, stored in liquid nitrogen at -196 degrees C for 6-88 days, thawed, and then cultured again. The number of islets recovered after this procedure was 80% of that present at the beginning. The viability of cultured/cryopreserved islets was then compared with that of islets from the same donor cultured for 24 hr, and was assessed by supravital staining, insulin response to glucose, and survival after implantation under the kidney capsule of nude rats. Supravital staining showed more nonviable cells in cryopreserved islets than in their cultured counterparts. Significant response to glucose was seen before and after cryopreservation in 2 of 4 sets of islets. Xenografts of 200 cultured islets (from 13 donors) were implanted in 15 nude rats under the kidney capsule, and a further 15 rats had cryopreserved islets (from the same 13 donors) similarly implanted beneath the kidney capsule. Two weeks later tissue was visible at the site of implantation in all 30 rats. Histological examination of both groups showed the tissue to have the morphology of islets, confirmed by immunohistochemical chemical localization of insulin. The insulin content of kidneys bearing 200 cultured islets was 7.88 +/- 1.6 mU (n = 13) versus 6.84 +/- 1.43 mU (n = 13) for kidneys bearing cryopreserved islets. Thus this technique for cryopreservation of isolated adult human islets enables a high recovery of endocrine tissue that survives after transplantation to nude rats, but some evidence of damage was apparent from insulin secretion studies and electron-microscopic studies. PMID- 3111040 TI - Traditional remedies and lead intoxication. AB - Three Saudi children suffered from lead intoxication as a result of ingestion of a preparation prescribed by a traditional practitioner. Two of them showed no symptoms of lead intoxication while the third child gave a history of symptomatic intoxication in the form of convulsions. The blood lead levels were increased in all patients and radiographic lead bands were seen in the long bones of the three children. The blood lead concentration was decreased by Na-Ca-EDTA and BAL treatment in the three patients. PMID- 3111041 TI - Circadian variations of the absolute eosinophil count and serum histaminase activity in tropical pulmonary eosinophilia. AB - Nine healthy volunteers and 25 tropical pulmonary eosinophilia (TPE) patients were used to study circadian variations of absolute eosinophil count (AEC) and serum histaminase activity (SHA). A marked circadian variation was found in AEC for healthy volunteers and TPE patients with the worst symptoms in the late evening and morning hours only; no rhythm could be detected in SHA for healthy subjects. However, TPE patients with worst symptoms in the late evening hours did exhibit a significant rhythm in SHA. Increased SHA in all TPE patients at all time-points of the 24 hour day-night cycle, irrespective of the worsening hours of symptoms in comparison to healthy controls, could be due to increased histamine production in such situations. PMID- 3111042 TI - [Electron microscopic study of the process of intermediate cell division in the cyst of the coccidian Sarcocystis muris]. AB - The intermediate cell is a third definitely outlined morpho-functional type of cells within sarcocysts, in addition to the two other well known ones--metrocytes and merozoites (Fedoseenko, Levit, 1979; Beyer et al., 1981). The intermediate cell divides by endodyogeny, the nuclear division being accomplished by semi closed pleuromitosis. In the dividing nuclei, centrioles and extranuclear bundle of microtubules connecting two pairs of centrioles are seen in addition to centrocones and associated semi-spindles. Pro-, ana- and telophases of mitosis have been followed. The microtubule organizing center (MTOC) seen in the cytoplasm of the intermediate cell is represented by the polar ring with microtubules originating from it. The MTOC is involved in the division of both the nucleus and the cytoplasm. The formation of the polar ring (MTOC) from the Golgi-adjunct has been first discovered and followed in the course of the intermediate cell division. PMID- 3111043 TI - [Poisson equalization of multicomponent cytofluorograms]. AB - A method of the Poisson fitting of flow cytometry data is suggested. The estimation of distribution parameters was carried out by the steepest descent method. The phagocytosis of fluorescent latex particles by murine macrophages was used as an experimental model. The results obtained by the Poisson fitting of cytofluorograms were in good agreement with the visual estimation of macrophage distribution with regard to the amount of uptaken particles. A high value of correlation index (more than 0.99) showed the validity of the suggested fitting method. The applicability of the method to cytofluorimetric analysis of human lymphocytes was successfully demonstrated. PMID- 3111044 TI - Neurofibromatosis and malignant childhood cancers: a survey in Italy, 1970-83. AB - Neural tumors, Wilms' tumor, rhabdomyosarcoma and several types of leukemia have been previously described in association with neurofibromatosis (NF). In a nation wide collection of cases in Italy, 15 children (0-14 years of age) with NF and cancer or leukemia were identified; 13 of them had been diagnosed with cancer between 1976-83. The expected number of children with cancer and NF in 1976-83 was 4.48. The distribution of tumor types was different from that found in the general population, with a higher proportion of tumors of neural crest origin as well as soft tissue sarcomas. In 7/15 the family history was positive for NF; in 5/7 the individuals affected included the mother and/or a maternal relative. PMID- 3111045 TI - Diminished production of interleukin 2 and gamma-interferon by cloned "T" cells from patients with the acquired immunodeficiency syndrome (AIDS). AB - A total of 76 T-cell clones established from peripheral blood (PB) of 2 patients with the acquired immune deficiency syndrome (AIDS) and of 141 T-cell clones established from PB of 3 normal donors were compared for their ability to produce interleukin 2 (IL-2) and gamma-interferon (gamma-IFN). Twenty-seven clones from AIDS patients and 85 clones from controls expressed the CD4 phenotype, whereas 49 clones from AIDS patients and 56 clones from controls expressed the CD8 phenotype. There were no significant differences in the proportions of IL-2 producing CD4 T-cell clones established from PB of patients with AIDS and controls, but the mean concentration of IL-2 produced by CD4 clones from AIDS patients was significantly lower than that produced by CD4 clones from controls. Both the proportion of gamma-IFN-producing CD4 clones and the mean concentration of gamma-IFN produced by CD4 clones were significantly lower in AIDS patients than in controls. In contrast, there were no differences between AIDS patients and normal individuals in the proportion of IL-2- or gamma-IFN-producing CD8 clones, or in the mean concentration of IL-2 and gamma-IFN produced by CD8 clones. These data suggest that the reduced ability of PB T-cells from patients with AIDS to produce IL-2 and gamma-IFN is not simply due to altered proportions or numbers of T-cell subpopulations, but also reflects intrinsic abnormalities of individual CD4 T lymphocytes. PMID- 3111046 TI - Cyclophosphamide, methotrexate,5-fluorouracil, alternating with adriamycin and mitomycin C in metastatic breast cancer: a pilot study. AB - To explore the clinical applicability of the Goldie and Coldman hypothesis, we treated 28 patients with metastatic breast cancer with alternating non-cross resistant chemotherapy. The patients received cyclophosphamide, 600 mg/m2, 5 fluorouracil, 600 mg/m2, methotrexate, 40 mg/m2, alternated every three weeks with adriamycin, 60 mg/m2, and mitomycin C, 10 mg/m2. Only one patient had previously received palliative chemotherapy. Six patients had received adjuvant CMF, and 17 patients had been pretreated with endocrine therapy (13 for advanced disease, 4 as adjuvant). Fourteen patients had bone involvement, and 10 had visceral metastases. A mean of 12 cycles was given to 24 evaluable patients. The objective response rate was 67%: 11 patients (46%) achieved complete and 5 (21%) partial remission. Response rate in soft tissues was 83.3%, in bone 50%, in liver 100%, and in lung 80%. The median duration of response was 14 months, with 7 patients still in remission. No life-threatening toxicity was observed. Our preliminary results support the validity of this approach and the efficacy of this combination chemotherapy. A large-scale randomized study is warranted. PMID- 3111047 TI - [20 ways to prevent tube feeding complications]. PMID- 3111048 TI - [Passive transport of Ca2+ in a myometrium mitochondria fraction]. AB - Na+, pH, prostaglandin F2 alpha are studied for their effect on Ca2+ transport into fractions of cow's myometrium mitochondria. Na+ does not affect a passive release of Ca2+ from mitochondria and its energy-dependent accumulation. A decrease of the incubation medium pH from 7.5 to 6.5 stimulates Ca2+ release from mitochondria and inhibits its energy-dependent pumping into them. Prostaglandin F2 alpha (10(-8)--2 X 10(-4) M) does not affect the activity of Ca2+ accumulation and release systems. A conclusion is made that the Na+-Ca2+-exchange system is absent in mitochondria of smooth muscle cells and Ca2+ release proceeds as a result of H+-Ca2+-antiport system functioning. PMID- 3111049 TI - [Isolation of antiserum against rat transcortin and characteristics of specific antibodies]. AB - Repeated chromatography of rat plasma protein on DEAE-cellulose, hydroxylapatite and subsequent gel-filtration through Sephadex G-200 were used to obtain a pure rat transcortin homogeneous upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. The molecular weight of transcortin was about 66 kDa as determined by SDS-polyacrylamide gel electrophoresis. Immunization of a rabbit with the homogeneous preparation of rat plasma transcortin caused development of antibodies to transcortin. It was shown that the antibodies of rabbit antisera in the experiments made in vitro and in vivo neutralized 60 and 65% of 3H-corticosterone-transcortin complexes, respectively. Specific antibodies to the transcortin were isolated from the homogeneous fraction of IgG by affinity chromatography on transcortin-sepharose 4B. 125J labelled antibodies were adsorbed by protein A-sepharose; IgG can be eluted by IM acetic acid as a sharp peak. The SDS-polyacrylamide gel electrophoresis demonstrated that affinity-eluted material contains 25 and 50 kDa polypeptides. PMID- 3111050 TI - [Acid-base equilibrium of the blood and oxygen metabolism during stress]. AB - The results of the investigation of the acid-base state of the arterial and venous blood have proved that during the emotional stress compensated metabolic acidosis develops. Respiratory alkalosis which is a compensatory shift results in the pronounced hypocapnia. The given state of the acid-base equilibrium is found under conditions of simultaneous transport violation and oxygen use by tissues. PMID- 3111051 TI - [Formalin treatment of severe radiation-induced hemorrhagic proctitis]. PMID- 3111052 TI - [Nitroglycerin-induced ECG changes are of prognostic value in unstable angina pectoris]. PMID- 3111053 TI - [Diverticulosis of the jejunum]. PMID- 3111054 TI - [Mucopolysaccharidoses]. PMID- 3111055 TI - [Development of erythrocyte antibodies in mothers of neonates with positive Coombs' reaction]. PMID- 3111056 TI - [Hormonal contraception with ethinylestradiol and gestoden. The effects on glucose tolerance and lipid metabolism]. PMID- 3111057 TI - Radical prostatectomy or radiotherapy in carcinoma of prostate. The dilemma continues. AB - Evaluation of the efficacy of radical prostatectomy versus radiotherapy in carcinoma of the prostate has been compromised by the scarcity of data in comparable populations. A nationwide search was conducted to compile the available data on the use of radiotherapy in lymphadenectomy-staged patients. The assessed population consists of patients with tumor confined to the gland (Stages A2 and B), negative staging lymphadenectomy, negative bone scan, and normal serum acid phosphatase level who received external beam radiotherapy with curative intent. To provide a broad spectrum of experiences, the search included patients from a large number of institutions including Stanford University, Washington University (St. Louis), those participating in the Radiation Therapy Oncology Group, and a broad range of radiotherapy practices surveyed by the PCS (Patterns of Care Study). A total of 209 patients were identified. No selection criteria other than the aforementioned were applied. The patients were treated consecutively during the survey period. In sharp contradistinction to the reported results of the VA Uro-Oncology Group the analysis indicates a less than 10 per cent probability of progression within the first five years after completion of treatment. Nationwide, the outcome of radiotherapy-treated patients appears to be equivalent to the comparable surgically treated population. PMID- 3111058 TI - Infectious agents and host responses. PMID- 3111059 TI - Modulation of mesangial cell contraction by arachidonate metabolites. PMID- 3111060 TI - Xenotransplantation of microencapsulated canine islets in diabetic mice. PMID- 3111061 TI - Shared idiotypes and restricted VH genes among murine autoantibodies of various specificities. AB - The autoantibodies studied here express cross-reactive idiotypes despite the fact that they are heterogeneous with respect to combining site. Furthermore, the presence of cross-reactive idiotypes is independent of the major histocompatibility complex, VH gene usage, and isotype. Similarly, VH gene usage shows that autoantibodies are derived from a restricted number of VH gene families. This restriction is independent of antigen specificity as well as the method of induction (i.e., spontaneous vs. induction). The observation that the VH 7183 gene is predominantly used suggests that certain autoantibodies may be derived from a unique set of B cells such as the Ly1+ B cells. It has been reported that these B cells secrete a high percentage of IgM autoantibodies. The studies reported here may provide greater insight into the genetic and immunoregulatory mechanisms by which autoantibodies arise. The precise mechanisms are not known but may involve both molecular (i.e., VH gene usage) and extracellular (i.e., idiotypic recognition) events. PMID- 3111062 TI - Amelioration of glomerular hyperfiltration in acute experimental diabetes mellitus by dietary myo-inositol supplementation and aldose reductase inhibition. PMID- 3111064 TI - [The effect of extreme temperatures on hematologic and biochemical indicators in heifers]. AB - The study was aimed at finding the effect of low and high temperatures on some biochemical parameters in heifers. Thirty half-sister heifers were used as the experimental material. The animals were divided into two groups. The experimental group including 16 heifers was kept loose on deep litter in an open barn with no thermal insulation. The control heifers (n = 14) were kept in a thermally insulated house. Blood was collected at extreme temperatures: above 30 degrees C and below -5 degrees C. An insignificant decrease of haemoglobin and haematocrit was recorded in the blood collected at low and high temperatures from the heifers kept in the open barn; a reduction of cholesterolaemia and total lipaemia was recorded at high temperatures. High and low temperatures significantly increased the concentration of free amino acids; the differences between the experimental and control group being from 36 to 76 mumol per litre. The content of 3.5-cyclic adenosine monophosphate was increased insignificantly at extreme temperatures. Hyperglycaemia was recorded in the heifers at high temperatures and at the beginning of the winter season. At low temperatures the concentration of thyroxine was found to be increased in the blood of the experimental animals: 120 nmol per litre and 161 nmol per litre vs. 95 nmol and 116 nmol in the control group. PMID- 3111065 TI - [Determination of delta aminolevulinic acid in the urine of cows in acute mass lead poisoning]. AB - The concentration of delta aminolevulinic acid (ALA) in the urine of dead heifers (n = 3), diseased cows (n = 13) and clinically healthy cows (n = 29) was determined in the course of acute mass intoxication with lead. At the same time, the content of lead was determined in kidney, liver, in rumen contents of dead heifers and in the beet pulp fed to the animals. The ALA concentrations were converted to values per uniform specific weight of urine and per gram of creatinine secreted with urine. As found, the determination of ALA concentration per gram of creatinine is diagnostically insignificant in the case of lead poisoning. The average ALA values in the urine of the dead and clinically diseased cows (221.0, 119.9 and 72.3 mumol per litre) markedly differed from the average values of ALA concentrations in the urine of the clinically healthy animals (41.2, 32.8 and 25.6 mumol per litre). Owing to the wide variability of the determined ALA concentration in urine it appeared useful in cases of suspicion of lead poisoning of cattle to determine ALA concentration in the urine of the group of clinically diseased animals and in the group of clinically healthy animals in order to compare ALA secretion with urine in the two groups. A 2.9-fold average increase of ALA in the urine of clinically diseased animals, compared with the ALA values in the urine of clinically healthy animals, already testifies to lead intoxication. PMID- 3111063 TI - Etiopathogenesis and biological behavior of feline vesicourachal diverticula. Don't just do something--stand there. AB - Asymptomatic microscopic urachal remnants located at the vertex of the urinary bladder are common in cats. Because they reduce the tensile strength of the bladder wall at this location, they represent risk factors for development of acquired macroscopic diverticula in cats with lower urinary tract disorders. Elimination of the underlying cause of lower urinary tract disease is frequently associated with resolution of acquired macroscopic vesicourachal diverticula. PMID- 3111067 TI - [Asymmetry of the digits in pigs as a hereditarily conditioned variation in the anatomic structure of the extremities]. AB - As follows from the population statistical investigation performed within the management information system, defects of the anatomic structure of the feet occur in the pig population of all breeds and cross combinations kept in the Czech Socialist Republic: the frequency of this occurrence is relatively higher than 4.4% (1984) and 3.8% (1985) of all litters affected by some of the genetic defects. In some populations different degrees of claw asymmetry occur in more than 40% of the individuals. Environmental conditions contribute to the severity of the defect (technology, particularly the type of floor), but the disposition is genetically conditioned. Prevention should mainly be based on the negative selection of the carriers of the undesired disposition. Working on this study, we used the results of the population statistical processing of the reports on the hereditary defects of pigs and the results of our own observations. In the former case the data concerned 29,778 pig litters, in the latter case 7343 pigs of the Large White, Landrace, Duroc and Prestice Black-Pied breeds. PMID- 3111066 TI - [Occurrence of coxiellosis and chlamydiosis in Sumava]. AB - The occurrence of antibodies to C. burnetii and Chl. psittaci was studied in the herds of cattle transported from southern Moravia to the pastures of the Sumava Mountains. Q-fever persists in latent state in the cattle grazing in the Sumava Mts. and causes no manifest infections in man. The finding of the rickettsia in the small mammals and their ectoparasites documents the probability of contact with the causal agent in the excretions of cattle in the pastures. Veterinary and human medical services should be aware of a possibility of occurrence of Q-fever and chlamydiosis not only in southern Moravia but also in the Sumava Mts. and in other areas. PMID- 3111068 TI - [Study of the reactivity and immunogenicity of a combined vaccine against abortion due to coxiellosis and chlamydiosis in sheep]. AB - Reactogenicity was studied in a combined vaccine against Q-fever and chlamydia induced abortion in ewes; the vaccine consisted of a mixture of purified corpuscles of Chlamydia psittaci (100 micrograms) and Coxiella burnetii (50 micrograms). The immunogenicity of the combined vaccine, evaluated by the number of positive serums after vaccination and by the average geometric titre of antibodies, was the same as that of the vaccine separate constituents as to the antibodies to C. burnetii, but somewhat higher in the case of antibodies to Chlamydia psittaci. When studied on a smaller number of ewes, the combined vaccine had an optimum immunogenicity in the cases of the prevalence of Chlamydia psittaci over C. burnetii in the vaccine. PMID- 3111069 TI - [Chromosome analysis of ducklings with a defective phenotype]. AB - In two equal periods, using the conventional method of processing bone-marrow cells after Konstantinov and Dobriyanov (1974), we studied the connection between the occurrence of chromosomal aberrations and deviations of phenotype. In the first part of the observation we found 8.5% numerical aberrations in 20 ducklings with retarded motility, torticollis and contractures of the fingers, compared with 1.27% in the control group with normal phenotype. In the second part of the observation the occurrence of aberrations in ducklings with defective phenotype of the same breeding dropped considerably to 1.7% and in the control group to 0.54%. The statistical evaluation of the results showed statistically significant differences (chi (4)2 = 56.78; p less than 0.05, and/or chi (4)2 = 27.74; p less than 0.05). PMID- 3111070 TI - Prolate pour-ons for the control of sarcoptic and chorioptic mange in cattle. PMID- 3111071 TI - Prevention of experimental haemorrhagic septicaemia with a live vaccine. AB - Pasteurella multocida serotype B:3,4 isolated from a fallow deer in England was used as a vaccine to prevent haemorrhagic septicaemia. The deer strain was less virulent for calves than typical serotype B:2 of haemorrhagic septicaemia strains. It elicited antibodies in cattle that protected mice against serotype B:2 infection. The live deer vaccine containing 2 X 10(7) viable organisms per dose was used to immunise calves. Six months after vaccination, five of six calves were protected against serotype B:2 challenge. Two calves challenged nine months after vaccination survived the same challenge. The live vaccine was more efficacious than an alum precipitated vaccine in protecting calves against B:2 challenge. PMID- 3111072 TI - Feeding lambs by stomach tube. PMID- 3111073 TI - Control of Listeria in the dairy plant. PMID- 3111074 TI - Fatty and hemorrhagic liver and kidney syndrome in breeding hens caused by aflatoxin B1 and heat stress in the Sudan. AB - Fatty liver in animals is commonly associated with toxic or nutritional disease. In tropical Africa, fatty liver in poultry is of considerable economic importance. However, it's occurrence and association with renal damage have not yet been reported. We now report the effects of hemorrhagic and fatty hepatorenal syndrome in Hybro breeding hens naturally exposed to heat stress and fed low level of aflatoxin B1. PMID- 3111075 TI - Evaluation of a solid-phase immunoassay (DIG-ELISA) for the serodiagnosis of ovine toxoplasmosis. AB - The antibody response to Toxoplasma gondii was studied in 5 experimentally infected sheep by means of the indirect fluorescent antibody test (IFAT) and the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA). A significant increase in the antibody levels was registered by both methods as early as one week after subcutaneous inoculation with the RH strain of T.gondii. Maximal antibody levels were recorded 4 to 8 weeks after the inoculation. Analysis of a total of 135 sera obtained during different stages of experimental or natural toxoplasma infection revealed close agreement between the results of the two methods used. The expediency of regular DIG-ELISA as well as of a modified procedure for the direct analysis of blood sampled onto filter paper discs was also demonstrated. There was a close correlation between the results obtained by analysis of serum and of blood adsorbed onto filter paper. PMID- 3111076 TI - Bovine IgM: does it fix guinea pig complement in the absence of bovine complement components? AB - Purified bovine isotypes IgM, IgG1, IgG2, and IgA (secretory), affinity purified with Brucella abortus, were tested in a complement fixation test (CFT) for their ability to activate guinea pig complement directly or in the presence of 'normal' bovine serum. Only IgG1 fixed guinea pig complement in the direct test and approximately 250 ng of antibody was required to activate 50% of 3 CH50 units with a standard amount of antigen. Addition of 'normal' bovine serum as an additional source of complement resulted in activation of guinea pig complement by IgM, IgG2 and secretory IgA at levels of approximately 1200, 700 and 2250 ng, respectively for 50% of 3 CH50 units. Addition of 'normal' bovine serum did not enhance complement activation by bovine IgG1. PMID- 3111077 TI - Immunohistological analysis of Rosai-Dorfman histiocytosis. A disease of S-100 + CD1-histiocytes. AB - Five cases of Rosai-Dorfman histiocytosis (RDH) (also called Sinus Histiocytosis with Massive Lymphoadenopathy; SHML) have been studied by immunohistochemical methods with heteroantisera and monoclonal antibodies. One case was also studied by Southern blot hybridization analysis with DNA probes specific for T cell receptor beta chain and immunoglobulin heavy chain. Immunophenotyping of large histiocytes, characteristic of RDH, evidenced the presence of S-100 protein and the absence of CD1 and other markers usually found in histiocytes and macrophages. DNA hybridization study showed the absence of clonal T or B lymphoid populations. PMID- 3111078 TI - Effect of volume depletion on the afferent arterioles in the avian kidney. AB - Nine white leghorn chickens were injected i.m. with furosemide (10 to 60 mg/kg body weight) twice daily for 18 days. The birds were then anesthetized with a combination of equithesin and diazepam and the kidneys perfused via the heart. Kidney tissue was sectioned serially and the granular epithelioid cells were counted in the juxtaglomerular apparatuses of the furosemide treated birds and in 3 normal chickens. Hyperplasia and hypergranulation of the epithelioid cells was found to occur in the juxtaglomerular apparatuses of both mammalian and reptilian type nephrons (with and without Henles loop) in the furosemide treated group. This finding was interpreted as an effect of hypovolaemia on the juxtaglomerular apparatuses. Furosemide caused an immediate stop in weight gain, an increase in the erythrocyte volume fraction and a sudden drop in blood pressure. The blood pressure later rose to subnormal levels. The heart rate was not altered. Plasma sodium and chloride fell significantly one day after furosemide administration and remained low throughout the experiment. Potassium fell during the second part of the experimental period. Captopril was injected after 18 days of furosemide treatment and lowered the blood pressure significantly. This was interpreted as indirect evidence for the presence of renin in the granular epithelioid cells and indicates the importance of the renin angiotensin system in maintaining the blood pressure in hypovolaemic conditions. PMID- 3111079 TI - Peanut lectin binding to the alveolar lining layer in hyaline membrane disease. AB - The authors have studied the histochemical pattern of Peanut lectin (PNA) binding sites in lungs of seven newborns with hyaline membrane disease (HMD) and ten controls. The alveolar lining layer was positive in HMD and no changes in the PNA pattern was noted after neuraminidase digestion. Hyaline membranes were generally unstained but occasional reactivity was encountered in some parts. No reaction with PNA was observed in control lungs, but positivity was seen after neuraminidase pretreatment. Our histochemical data document the presence of accessible galactosyl residues with absence of terminal sialic acid in the alveolar lining layer of newborns with HMD. The authors suggest that PNA reactivity in HMD reflects an histochemical feature described in fetal lungs at the pseudoglandular and canalicular stages. PMID- 3111080 TI - Thinning of fetal pulmonary arterial wall and postnatal remodelling: ultrastructural studies on the respiratory unit arteries of the pig. AB - Adaptation to extra-uterine life and postnatal remodelling of intra-acinar arteries was followed in 34 Large White pigs, from birth to adult life, applying morphometry to light and electronmicroscopic studies. After birth, percentage wall thickness decreased rapidly due to a reduction in overlap of adjacent smooth muscle cells and an increase in smooth muscle cell surface area/volume ratio, (p less than 0.01 at 12 h), without a reduction in the volume density of smooth muscle cells. Smooth muscle cells appeared immature at birth and synthetic rather than contractile organelles predominated. Between 3 weeks and 6 months myofilament volume density doubled (p less than 0.0001). At all ages, pericytes, intermediate and smooth muscle cells showed similar volume densities of contractile and synthetic organelles. Thus, the high fetal pulmonary vascular resistance appeared to be due to the shape and arrangement of smooth muscle and other contractile cells within the vessel wall, rather than an excessive contractility of these cells. After birth rapid remodelling of arterial wall structure achieved a reduction in wall thickness by 30 min, continuing during the first week of life. After 3 weeks, remodelling involved an increase in wall thickness, connective tissue deposition with more collagen than elastin (p less than 0.0001), and smooth muscle cell differentiation. PMID- 3111081 TI - Splenic haematopoiesis in patients with cirrhosis of the liver. AB - Hitherto it has generally been assumed that splenic haematopoiesis in adult humans occurs very infrequently and is predominantly associated with haematological disorders. In the present study of patients with cirrhosis of the liver, a marked splenic haematopoiesis was a constant finding. Moreover, low level splenic erythro- and granulopoiesis was highly prevalent even in haematologically normal controls, while splenic thrombopoiesis was conspicuously absent in both groups. We suggest that splenic haematopoiesis results from entrapment and proliferation of circulating haematopoietic precursor cells in the splenic red pulp. This would account for the presence of splenic haematopoiesis in normal controls as well as in patients with cirrhosis of the liver. In the latter, stimulation of bone marrow haematopoiesis and increased splenic pooling of haematopoietic precursor cells may contribute to the marked increase of splenic haematopoiesis observed. PMID- 3111082 TI - Instability of v-src sequences in nonhuman primate tumors cultured in vitro. AB - We have analyzed the DNA of marmoset tumors induced and marmoset cells transformed by Rous sarcoma virus (RSV) and derivative viruses of various types. Southern blot hybridization was used to determine the presence of v-src gene sequences. We failed to detect v-src DNA in high-passage cells derived from marmoset tumors induced in vivo or from marmoset cell lines transformed in vitro. The inability to detect src sequences was not related to selection of revertants in culture, since all cell lines retained transformed morphology and cells transformed in vitro retained the ability to induce sarcomas after transplantation into adult allogeneic marmosets. By contrast, we detected integrated proviruses in cells analyzed 32 to 60 days after in vitro transformation. The proviral sequences appeared to be identical to the transforming virus but were apparently unstable and continued to transpose. PMID- 3111083 TI - Effect of 3'-azido-2',3'-dideoxythymidine (AZT) and neutralizing antibody on human immunodeficiency virus (HIV)-induced cytopathic effects: implication of giant cell formation for the spread of virus in vivo. AB - The effect of 3'-azido-2',3'-dideoxythymidine (AZT) on the human immunodeficiency virus (HIV)-associated giant cell formation was studied in vitro. For this purpose we developed a coculture system using Molt-4 and its virus-producing cell, Molt-4/HTLV-III, which induced syncytia very efficiently. Treatment of the cocultures with 1 and 5 microM of AZT did not inhibit induction of multinucleated giant cells, although only 0.1 microM AZT resulted in almost complete inhibition of HIV replication in Molt-4 cells by cell-free virus infection. This was also evidenced by the assays for viral antigen-positive cells, reverse transcriptase activity, and virus particles released from cell cultures after AZT treatment. When the cocultures were treated with 1% neutralizing antibody (NA) from HIV infected individuals alone, giant cell formation was inhibited to some extent. However, the concomitant treatment of culture with AZT and NA resulted in much stronger inhibition of giant cell formation. The amount of CD4 antigens on the surface of cells was reduced greatly in the HIV producer cells (Molt-4, H9, and MT-4 cells) as compared to their HIV-free counterparts. These data suggest that (1) both CD4 antigen and viral antigens on the surface of cells play central roles in the induction of multinucleated giant cells and (2) AZT is more effective in inhibition of viral spread in patients with higher NA, probably at an earlier stage of the disease than in patients with lower NA titer. PMID- 3111084 TI - [Use of intal electrophoresis in the combined treatment of patients with vasomotor rhinitis]. PMID- 3111085 TI - [Contact-activated and immunoreactive prekallikrein in the plasma of patients with hypertension]. AB - Alterations in activity of kaolin-activated (contact-activated, CA) and immunoreactive (IR) prekallikrein were studied in blood plasma of healthy persons and of patients with hypertension under conditions of rest and of dose-dependent physical loading. CA prekallikrein was dissimilarly altered depending on the type of hemodynamic structure of the pressure reaction (arterial pressure): content of CA prekallikrein was increased in hyperkinetic type and--decreased in hypokinetic type. Content of IR prekallikrein, measured by means of radial immunodiffusion using monospecific antiserum, was similar in healthy persons and in the patients at rest and after physical exercises. It was increased slightly but did not correlate with CA prekallikrein alterations. As content of CA- and IR prekallikreins did not correlate in the disease dynamics and after physical exercises, functional impairments may cause activation of blood plasma prekallikrein in hypertension. A procedure for isolation of highly purified preparation of kallikrein, production of monospecific antiserum to prekallikrein are described. Immunochemical studies and quantitative estimation of IR prekallikrein were carried out. PMID- 3111086 TI - [The type of interaction of macrophages with serum low-density lipoproteins partially hydrolyzed by pepsin]. AB - Effect of partial proteolysis of 125I-low density lipoproteins (LDL) from blood serum on their interaction with a culture of mice peritoneal macrophages was studied. Absorption and degradation of the LDL by macrophages was distinctly increased after 10% hydrolysis with pepsin. Degradation of 125I-LDL, hydrolyzed partially by pepsin, in the cells was less inhibited by unlabelled native LDL as compared with unlabelled but modified with pepsin LDL. Macrophages appear to contain specific sites for binding of LDL hydrolyzed partially by pepsin; these sites were distinct from receptors for acetylated LDL as shown by competitive analysis. PMID- 3111087 TI - Modified glycine precipitation technique for the preparation of factor VIII concentrate of high purity and high stability. AB - A modification of the glycine precipitation method for the production of factor VIII concentrate is reported. In this procedure, cryoprecipitate was prepared, washed and dissolved in buffer. Contaminating fibrinogen was precipitated by the addition of 2.8 M glycine buffer at 30 degrees C. The fibrinogen precipitate was removed by filtration using a layer of glass beads. Factor VIII was then precipitated from the filtrate by adding solid NaCl. After centrifugation, the precipitate was resuspended in buffer, desalted, sterilized by filtration, lyophilized and subjected to dry-heat treatment. The procedure gave a good recovery of factor VIII (280 IU/l) and seems applicable to large-scale production. The resulting factor VIII concentrate was especially characterized by its high purity (10 IU/mg) and stability both in the liquid state and during dry heat treatment. PMID- 3111088 TI - Assessment of multimeric structure and ristocetin-induced binding to platelets of von Willebrand factor present in cryoprecipitate and different factor VIII concentrates. AB - The multimeric structure of von Willebrand factor (vWF) and its ristocetin induced binding to platelets, using a simple and very sensitive radiomonoclonal antibody-labeled vWF method, was compared in normal plasma, single-donor cryoprecipitate (CP) and five different antihemophilic factor (AHF) concentrates. All the AHF showed a lack of larger vWF multimers, an abnormal 'triplet' pattern, and much lower vWF binding to platelets than that of plasma or CP, vWF being the lowest for those with a lesser proportion of larger vWF multimers. These results suggest that the combination of vWF multimeric analysis and the radiomonoclonal labeled vWF method may be very useful in the assessment of AHF preparations. PMID- 3111089 TI - Tri(n-butyl) phosphate/detergent treatment of licensed therapeutic and experimental blood derivatives. AB - Incubation of an AHF concentrate with 0.3% tri(n-butyl)phosphate (TNBP) and 0.2% sodium cholate was shown to inactivate at least 10,000 infectious doses of lipid enveloped viruses, including hepatitis B and non-A, non-B viruses and HTLV-III [Prince et al., Lancet i, pp. 706-710, 1986]. The use of TNBP/detergent combinations for virus sterilization was evaluated further to determine its effect on the structure and function of a wide variety of blood proteins. Vesicular stomatitis and Sindbis viruses were used as markers of virus inactivation. TNBP/detergent treatment did not significantly alter the function of AHF, factor VII, factor IX, factor X, fibrinogen, factor XIII, fibronectin, anti-HBsAg and anti-HA in normal serum globulin, haptoglobin, tumor necrosis factor, alpha-interferon, and both native and chemically polymerized stroma-free hemoglobin. As compared with partially purified derivatives, the extent of virus sterilization of plasma and component cryoprecipitate with 0.3% TNBP and 0.2% sodium cholate at ambient temperature could be improved by raising the TNBP concentration and temperature. Virus sterilization by TNBP/detergent mixtures appears to be generally applicable to blood protein derivatives. PMID- 3111090 TI - Standardization of bromelin for use in routine one-stage antibody screening. AB - A simple standardization method for bromelin used in routine one-stage antibody screening is described. Bromelin proteinase activity was assayed using casein as the substrate, and converted to units. The use of proteinase activity units for standardization of bromelin resolves differences between commercial preparations. PMID- 3111091 TI - Murine monoclonal antibody suitable for use as an Rh reagent, anti-e. AB - The production by the hybridoma technique of a monoclonal antibody which behaves as an anti-e agglutinin is described. A reagent was made from ascitic fluid diluted in RPMI 1640 culture medium and bovine serum albumin. All red blood cells bearing the e antigen were agglutinated; no reactivity was recorded with untreated EE red cells suspensions. However, cross-reactivity was observed with enzyme-pretreated EE cells. The characteristics of this monoclonal antibody are described and are in accordance with the standard references. PMID- 3111092 TI - Gm allotyping to determine the origin of the anti-D causing hemolytic anemia in a kidney transplant recipient. AB - Anti-D causing mild hemolytic anemia was found in the serum and on the red cells of a D-positive patient who had received a kidney transplant from his D-negative mother. Anti-D had been detected in the donor's serum before transplantation. Gm allotyping of the patient's serum, donor's serum, donor's anti-D, and the unexpected anti-D in the posttransplantation serum showed the antibody to be of maternal origin. The patient was Gm(fb), the donor Gm(agfb), the maternal anti-D Gm (afb), and the anti-D in the posttransplantation serum was Gm(a). PMID- 3111093 TI - Excess of blood group B in primary myelofibrosis. AB - The distribution of ABO and Rhesus (D) blood groups was studied retrospectively in 40 patients with primary myelofibrosis (PMF). Only patients with a leukoerythroblastic peripheral blood, splenomegaly and marrow fibrosis in whom chronic myeloid leukemia and secondary myelofibrosis was absent were included in the study. In 14 patients (35%), PMF was preceded by another myeloproliferative disorder (polycythemia rubra vera, essential thrombocythemia or unclassified myeloproliferative disorder), while 26 patients (65%) represented agnogenic myeloid metaplasia (AMM). Comparison with Hospital and Irish blood group distribution showed a significant increase in blood group B (p less than 0.01) in PMF. This increase remained statistically significant for both the AMM and the non-AMM subgroup of PMF when each subgroup was considered separately. This finding supports previous suggestions that the various myeloproliferative disorders which proceed to myelofibrosis are a closely related group rather than a heterogeneous collection of diseases. PMID- 3111094 TI - Use of plasma segments for estimating factor VIII activity in pools of fresh frozen plasma. AB - This study describes a procedure for estimating the factor VIII activity of pools of fresh frozen plasma destined for fractionation into factor VIII concentrates. This information is useful for estimating overall yields. We compared the factor VIII activity of plasma packs and the attached segments shortly after the production of fresh frozen plasmas, during storage at -30 degrees C for up to 4 weeks, after shipping at -20 degrees C to the fractionation site, after storage at -30 degrees C at the fractionation site, and after cryoprecipitation. The factor VIII activity of the segments and the plasma packs were indistinguishable at all stages except after cryoprecipitation. Our results suggest that, prior to the cryoprecipitation stage, a pool of a representative number of plasma segments can be used to determine the factor VIII activity of the plasma pool to be fractionated. PMID- 3111095 TI - [Characteristics of the precipitation of the antigenic structures of the tick borne encephalitis virus using polyethylene glycol and ammonium sulfate]. AB - When immunoelectrophoretic methods were used for analysis of tick-borne encephalitis (TBE) virus antigens, TBE virus virion antigen (VA) from the virus containing tissue culture fluid sedimented upon addition of polyethylene glycol (PEG) up to 7% whereas upon addition of ammonium sulphate (AS) the bulk of VA sedimented in the range of 40-70% salt saturation. The non-virion antigens (NA) sedimented at all PEG (up to 22%) and AS (up to 70% saturation) concentrations. In stringent ultracentrifugation procedure (12-13 X 10(6) g X min), the bulk of VA and a small portion of NA are pelleted. Repeated ultracentrifugation results in sedimentation of additional amounts of VA and NA. The sedimentable NA are pelleted by low PEG (up to 5-7%) and AS (up to 20-30%) concentrations and differ in their interaction with antibodies in the course of immunoelectrophoresis from nonprecipitatable ("soluble") NA. Combined sedimentation of antigens with AS (in the range of 40-70% saturation), intensive dialysis and subsequent sedimentation with low and high PEG concentrations produces homogeneous antigenic preparations containing VA or "soluble" NA. PMID- 3111096 TI - [Possibility of transferring patients with type-II diabetes mellitus treated with small doses of sulfonylurea preparations to diet therapy]. AB - Nine patients with diabetes mellitus, type II (6 males and 3 females) were studied. The average duration of the disease was 7.1 years. The patients were perorally treated with glibenclamide (5-10 mg daily). Beta-cellular function was studied with glucagon as well as the peripheral insulin sensitivity of the patients on the background of the peroral treatment and after its two-week discontinuation--on the background of dietetic treatment. No significant difference in beta-cellular function, insulin sensitivity and metabolic compensation was established. Part of the patients with diabetes mellitus, type II, treated with low and medium doses of glibenclamide, could well be compensated only by an adequate diet. PMID- 3111097 TI - [Factor VIII (von Willebrand antigen) in patients with acquired thrombocytopathies]. AB - Factor VIII/von Willebrand antigen (VA), part of the molecule of plasma factor VIII, realizes the interaction between platelets and vascular endothelium and the triggering of primary hemostasis. The modern diagnostics and treatment of the complicated acquired thrombocytopathies are impossible without the investigation on the concentration of factor VIII/von Willebrand antigen. The immune coagulation method used allows the objective, exact and fast determination of VA- referent values have been developed in healthy subjects. The patients with blastic leukosis studied--28 and with chronic myeloleukemia--18, all with severe endogenous complicated thrombocytopathy, functionally and biochemically confirmed, showed normal values of VA/von Willebrand antigen. On the contrary, a slightly elevated VA was established in patients with diabetes with no vascular degenerative syndrome, corresponding to the activation of platelet functions and to enhanced adhesiveness in particular, contributing to thrombotic complications. The data obtained are discussed in connection with the etiopathogenesis of the separate kinds of thrombocytopathies and the necessity of substitutive therapy. PMID- 3111098 TI - Chronic lymphocytic (autoimmune) thyroiditis in children. AB - Chronic lymphocytic (autoimmune) thyroiditis is one of the most common causes of non-toxic goiter in children and accounts for most of the acquired juvenile hypothyroidism. Asymptomatic goiter is the most common presentation though subclinical hypothyroidism and growth failure are frequently seen. Thyroid function is variable depending on the degree of thyroid destruction. Thyroiditis is the prototype of autoimmune diseases. Thyroglobulin or microsomal antibodies are present in serum of virtually all individuals. Cellular destruction is currently thought to be related to a dysfunction of suppressor T-lymphocytes, allowing appearance of "forbidden clones" of helper T-lymphocytes which stimulate production of cytotoxic auto-antibodies against thyroid tissue. The resultant lymphocytic infiltration, disruption of thyroid follicles and fibrosis produce the typical pathologic and clinical picture of an enlarged, firm thyroid with gradual loss of thyroid function. In children, the process may arrest before complete loss of thyroid function and spontaneous recovery occurs. Those who become hypothyroid must take thyroxine supplement. PMID- 3111099 TI - [Lisuride in the combination treatment of Parkinson disease]. AB - Lisuride, a semisynthetic dopaminergic ergot derivative, was administered in 34 patients with Parkinson's disease (mean age 67.5 years, average duration of illness 7.1 years, mostly stage IV) in an average oral dosage of 1.2 to 1.5 mg (range 0.4 to 3.0 mg) in addition to basic treatment with levodopa and decarboxylase inhibitor. Duration of combined treatment was 3 to 44 months. Daily dose of levodopa could be reduced by 13 to 34%. In the short-term group (3 months) the total disability score improved by 50%, and in the long-term group (up to 44 months) by 46%, with improvement of rigidity, tremor, speech and repeated movements, less of bradykinesia. Similar to treatment with dopamine agonists, after 18 to 24 months, despite increased dosage of levodopa, a slight increase of some clinical features of parkinsonism, particularly bradykinesia and gait disorders, were observed. Daily fluctuation and on-off symptoms often improved in intensity, but were eliminated only in a small number of patients. Discontinuation of lisuride due to adverse effects was necessary in 17.6%. Often, however, preexisting adverse effects of levodopa therapy, particularly psychiatric complications, responded favorably. Lisuride is a new effective agent in the combination treatment of advanced stages of parkinsonism. PMID- 3111100 TI - [3-year long-term therapy of recurrent duodenal ulcer with 400 mg cimetidine nocte]. AB - 253 patients were treated for 3 years with 400 mg cimetidine at night to prevent relapses of recently healed duodenal ulcers. The efficacy of maintenance treatment was evaluated on a life table basis. In contrast to previous studies not the first but the third symptomatic relapse was taken as the major criterium of treatment failure, an assumption, that better represents the everyday practical situation. Further endpoints for the life table calculation were: the wish of the patient to stop treatment after the first or second recurrence, the failure of a first or second recurrence to heal within 12 weeks and side effects. At 1, 2 and 3 years 5 +/- 2.4%, 16 +/- 4.6% and 20 +/- 5.2% respectively had to be considered as treatment failures. 4 patients presented with a bleeding relapse, none of which necessitated emergency operation. There were no irreversible side effects. This study demonstrates that treatment of recurrent duodenal ulcers with 400 mg cimetidine at night for 3 years is safe and improves considerably the quality of life of the majority of patients. The authors suggest that drug maintenance treatment should be offered before surgery is recommended. PMID- 3111101 TI - [Dose-related effect of dexamethasone on the poly-(ADP ribose) synthesis of human lymphocytes]. AB - Poly (ADP-ribose) synthesis and DNA synthesis after medication of dexamethasone was determined in 16 cases. Poly (ADP-ribose) synthesis in peripheral lymphocytes decreased after low dose dexamethasone. In a second trial with double doses of dexamethasone no significant decrease of Poly (ADP-ribose) in relation to DNA synthesis could be shown. There seems to be a connection between suppression of Poly (ADP-ribose) and cell cyclus of lymphocytes, specially the S-phasis of lymphocytes. The decrease of Poly (ADP-ribose) synthesis after cortisone medication is dosis connected. Dosis, interval of dosis and over all dosis are closely related to the effect of immunosuppression of this steroidal hormone. PMID- 3111102 TI - WHO Expert Committee on Biological Standardization. Thirty-sixth Report. PMID- 3111103 TI - WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirtieth report. PMID- 3111104 TI - Prevention and control of intestinal parasitic infections. Report of a WHO Expert Committee. PMID- 3111105 TI - Evaluation of certain food additives and contaminants. Thirtieth Report of the Joint FAO/WHO Expert Committee on Food Additives. PMID- 3111106 TI - Metabolism of 2,3,4',6-tetrachlorobiphenyl: formation and tissue localization of mercapturic acid pathway metabolites in mice. AB - 2,3,4',6-Tetrachlorobiphenyl (tetraCB) and the corresponding 14C-labelled compound (14C-tetraCB) were synthesized. Two reference compounds, 4-methylthio- and 4-methylsulphonyl-2,3,4',6-tetrachlorobiphenyl were also prepared and characterized. TetraCB and 35S-cysteine were given to groups of female mice. Formation of methyl[35S]sulphonyl-tetraCB was indicated by the presence of extractable sulphuric acid-soluble radioactivity in lung, liver, kidney and fat of the tetraCB-treated mice. As demonstrated by gel permeation chromatography followed by gas chromatography-mass spectrometry, the tissues of the tetraCB treated mice contained mainly methylsulphonyl-tetraCB, minor amounts of tetraCB and traces of methylthiotetraCB. The major compound present in lung was 4 methylsulphonyl-tetraCB, indicating the presence of specific binding sites for this metabolite in lung tissue. According to autoradiography of mice injected with 14C-tetraCB, these binding sites were present mainly in the tracheo bronchial mucosa. PMID- 3111107 TI - Induction of xenobiotic-metabolizing enzymes and peroxisome proliferation in rat liver caused by dietary exposure to di(2-ethylhexyl)phosphate. AB - Exposure of rats to 1% or 3% (w/w) di(2-ethylhexyl)phosphate in the diet for five days results in two- to three-fold inductions of liver cytosolic epoxide hydrolase activity and microsomal cytochrome P-450 content. Cytochromes P-450b + e were induced 20- to 35-fold, but no increase was observed in cytochrome P-450c. Considerably smaller effects were obtained on NADPH-cytochrome c reductase, microsomal epoxide hydrolase and microsomal cytochrome b5 content, and there was no effect on cytosolic glutathione transferase activity, under the same conditions. A dramatic increase in cyanide-insensitive palmitoyl-CoA oxidation and total mitochondrial protein, together with smaller increases in total catalase and cytochrome oxidase activities, were observed after treatment with di(2-ethylhexyl)phosphate, indicating that this compound causes proliferation of both peroxisomes and mitochondria. It is suggested that the induction of cytosolic epoxide hydrolase and the proliferation of peroxisomes may be related processes. PMID- 3111108 TI - The effect of intravenous tissue-type plasminogen activator in a rat model of embolic cerebral ischemia. AB - Thrombolytic agents may be useful in the treatment of cerebral ischemia caused by arterial thrombosis or embolic occlusion. A trial of intravenous human tissue type plasminogen activator (rt-PA) was carried out in seven male Sprague-Dawley rats subjected to embolic cerebral ischemia, with eight control animals. One-hour old autogenous blood clot was injected into the internal carotid artery. A 30 minute infusion of 10 micrograms/kg/minute of rt-PA or saline followed. Areas of ischemia at two hours post-embolization were assessed by digital image processing of serial iodo-14C-antipyrine autoradiographic images. The volumes of "no-flow" (NF) and "low-flow" (LF) regions were calculated. One animal in each group suffered no detectable ischemia; the remainder had well-defined regions of middle and posterior cerebral artery ischemia. No animal sustained a hemorrhagic lesion. Treatment produced no noticeable effect on the patency of cervical vessels. Total NF and LF volumes were less for the treated group but did not reach statistical significance by t-test. In middle cerebral distribution sections, however, LF volume was significantly less (p less than 0.05) for treated animals (150 vs. 191 mm3), primarily due to a more significant decrease in LF volume in the anterior middle cerebral overlap zone (47 vs. 90 mm3; p less than 0.025). Fibrinogen levels were not altered by drug treatment (p greater than 0.30). PMID- 3111110 TI - Distribution of vitamin A in various organs of rats in relation to the quality and the quantity of dietary proteins. AB - The influence of the quality and the quantity of dietary proteins on the distribution of a single massive dose of vitamin A in various organs of growing Wistar strain rats has been studied by using casein and bengal gram diets at 20% and 10% protein levels. The distribution of [3H]-retinyl acetate in various tissues was also investigated in these dietary conditions. The results show that the hepatic storage of dietary as well as a single massive dose (20,000 I.U.) of vitamin A was profoundly decreased in the rats fed on bengal gram diets as compared to those fed on casein diets. Regardless of hepatic stores, the plasma vitamin A levels were comparable in all the groups. Feeding of low quality of protein reduced the tissue distribution of [3H]-retinyl acetate in control as well as rats given a massive dose of vitamin A. This study suggests that both the poor quality and the inadequate quantity of dietary protein are detrimental influences on the vitamin A status of the growing rats. PMID- 3111111 TI - [Is testicular biopsy still a current andrologic study method?]. AB - In the course of decades, the indications for testicular biopsy have significantly changed with the development of hormone estimation and chromosomal analysis. Today modern andrological techniques may replace the biopsy in many cases. On the basis of an exactly defined history and thorough clinical, spermatological, and endocrinological investigations, however, there may be some situations which call for a testicular biopsy in order to settle questions still unclear in the evaluation of male infertility. In addition, modern techniques allow exact histological and cytological evaluation. Therefore, histological examination of testicular tissue is frequently of prognostic value. Besides the andrological indications, the increased incidence rate of so-called atypical germ cells in testicles of infertile men represents an additional oncological indication for testicular biopsy. PMID- 3111109 TI - Experimental models of chronic focal epilepsy: a critical review of four models. AB - A number of experimental (i.e., animal) models have been developed to induce chronic focal epilepsy. Three of the most commonly employed are the alumina cream, kainic acid, and the electrical kindling techniques. A fourth approach involving the application of minute quantities of tetanus toxin to discrete brain sites, although relatively under-utilized, may be favorably compared to the aforementioned models. PMID- 3111112 TI - [Angiolymphoid hyperplasia with eosinophilia. The spectrum from Kimura disease to atypical pyogenic granuloma]. AB - A patient showed the "atypical pyogenic granuloma" of the head in combination with atopic dermatitis and proceeding pyogenic granuloma of the back. The diagnostic aspects of angiolymphoid hyperplasia with eosinophilia (ALHE) including Kimura's disease, subcutaneous ALHE, and atypical pyogenic granuloma are discussed. PMID- 3111113 TI - [Hormone studies in andrology]. AB - Investigation of endocrine function is mainly performed by measuring plasma levels of the hormones concerned. Their evaluation must take into account the spontaneous alterations of hormonal plasma levels. With regard to gonadotrophins, the short-term episodic peaks of LH are significant. Testosterone levels, as well, show extensive short-term variations; in addition we find a marked circadian rhythm. Seasonal variations of longer duration are possibly superposed. Regarding the evaluation of testosterone levels, we must consider its protein binding. Only the free fraction of the hormone is biologically active. Concerning the function and secretory capacity of endocrine organs, stimulation tests often provide us with better results than the determination of basal plasma levels. The gonadotropic function of the hypophysis can be stimulated by intravenous application of 100 micrograms GnRH leading to increased blood levels of LH and FSH. The stimulation of the testosterone biosynthesis is achieved by application of hCG. The testosterone plasma levels rise within a few hours; a second peak follows after about 48 hours. Functional tests are also significant regarding the therapeutical prognosis of spermatogenetic disorders treated with gonadotrophins. Their outcome is even better if the secretory capacity of the hypophysis and the Leydig's cell apparatus has been proved sufficient before treatment. PMID- 3111114 TI - Formula for calculating vaccine profitability. AB - A mathematical formula is developed for calculating the profitability of real or stimulated vaccination campaigns, in relation to the years elapsed since the vaccination date and within the period of immunity given by the vaccine. According to the formula, profitability depends on the annual attack rates and corresponding costs, vaccine price and efficacy, and number of postvaccination years considered. The factors that do not affect profitability are values of local currency, annual discount rates and the absolute number of vaccines, provided the relative proportion of subjects vaccinated is maintained constant among the distinct risk groups, when comparing different policies. Examples of vaccinations against hepatitis B and measles are presented. PMID- 3111116 TI - [Ultrastructural analysis of penicillinase-producing strains of Neisseria gonorrhoeae isolated from patients with a recurrence of the disease]. PMID- 3111115 TI - Was it the gun under the mattress? PMID- 3111117 TI - [Protective properties of the gonococcal L-antigen]. PMID- 3111118 TI - [Detection and clinical picture of gonorrhea in women in the postabortion period]. PMID- 3111119 TI - The surface charge of L-A9 cells and Aedes albopictus cells infected with Marituba (Bunyaviridae) virus. AB - The surface charge of Marituba virus infected L-A9 cells and Aedes albopictus cells was estimated by direct measurement of their electrophoretic mobilities. Uninfected L-A9 cells and A. albopictus cells have mean electrophoretic mobilities of -1.083 microns/s X cm/V and -1.019 microns/s X cm/V, respectively. In Marituba virus infected L-A9 cells a progressive decline in the electrophoretic mobility was observed. In contrast, in Marituba virus infected A. albopictus cells the electrophoretic mobility of the cell surface was unaltered. PMID- 3111120 TI - [Predilection sites of infantile skull fractures following blunt force]. AB - Previous investigations on calvarial fractures in infants have shown that the flexibility and displacement of the infant calvarial are not sufficient to avoid fractures as a result of fall. From a table height onto hard ground - and in special cases, fractures cannot be avoided even after falls onto softly cushioned ground. The skull fractures are located in paper-thin, transparent, single-layer bone areas without diploe. The results of previous literature were compared with investigations of the skulls of 82 infants (from neonates up to infants 14 months of age). Congenital fissures, cranioschisis, locally retarded ossification in the cranium and craniotabes are all weak points where fracture has a tendency to occur even if the impact is minor. These ossification defects are increased in the ossa parietalia, but can also be found in the os frontale or in the os occipitale. The location is not always the same but can be detected by locating the skull transparency using diaphanoscopy. PMID- 3111121 TI - [Therapy of advanced prostate cancer]. AB - The carcinoma of the prostate gland is a malignant tumour like the other. The locoregional carcinoma of the prostate gland is locally curatively treated with prostatovesiculectomy, percutaneous high-voltage therapy or interstitial radiotherapy. The disseminated diseases of the prostate gland is systemically palliatively treated. A survey is given of the forms of therapy for the advanced carcinoma of the prostate gland. The estrogen therapy has its justification still nowadays. With the preparation Turisteron (ethinylestradiol propansulphonate) of the VEB Jenapharm an oral depot estrogen is at our disposal, which has distinctly smaller side effects than diethylstilbestrol (DES). PMID- 3111123 TI - [Propicillin in dental practice]. PMID- 3111122 TI - [Conservative therapy of prostate cancer using Turisteron]. AB - Turisteron is an orally highly effective depot estrogen (ethinylestradiol sulfonate) with relatively slight side effects. The treatment with Turisteron is very effective and is well tolerated by the patient. A strong antiandrogenic effect could be produced which had as its sequel a significant increase of the survival rates of patients with carcinoma of the prostate gland. The weekly dosage of 2 mg Turisteron led to a decrease of the biologically active, free testosterone to less than 2% compared with the initial value. The decrease of the total testosterone to castration values and the decrease of the free testosterone still significantly below values of castration are evidences for the strong antiandrogenic effect in exclusive estrogen treatment with Turisteron. From this conclusions relevant to practice were derived and finally therapy recommendation for the conservative treatment of the carcinoma of the prostate gland were given. PMID- 3111124 TI - Characteristics of a soil-isolated Bacillus subtilis phage, GS1, and GS1-mediated plasmid transduction. AB - A previously described soil-isolated Bacillus subtilis bacteriophage, GS1, was further characterized. It is a tailed phage with regular head morphology and a discrete base plate. GS1 belongs to morphological group A1 of Bacillus phages. Its tail measured 170 nm and the head width was 92 nm. GS1 produced turbid plaques on its natural host strain, but clear plaque variants occurred at high frequency. All attempts to transduce either erythromycin (Em) or tetracycline (Tc) resistance markers, present in soil-isolated phage-sensitive bacilli, failed. Erythromycin resistance plasmid pE194, introduced into B. subtilis by protoplast transformation, was transduced among B. subtilis strains at a frequency of 10(-6) to 10(-7). PMID- 3111125 TI - Degradation of gallic acid by Aspergillus flavus. AB - Aspergillus flavus utilized gallic acid as sole carbon source and increased in presence of glucose and sucrose. The enzymes were inducible in nature and during degradation of gallic acid. 4-carboxy, 2-hydroxy cis, cis-muconic acid and pyruvic acid were detected. The estradiol (meta) fission of gallic acid by A. flavus was postulated. PMID- 3111126 TI - [Relation between hyperprolactinemia and polycystic ovary syndrome]. AB - The authors compared 12 hyperprolactinemic patients with polycystic ovary (PCO) syndrome to 12 patients with galactorrhea-amenorrhea (GA) syndrome. Luteinizing hormone-releasing hormone (LH-RH) and thyreotropin-releasing hormone (TRH) tests were performed at the same time in every case to determine the reactivity of the pituitary gland. The distinctive features of the PCO syndrome were beyond the clinical symptoms the characteristic ovarian structure verified by ultrasound examination, as well as the elevated serum LH, testosterone levels and the estradiol concentration at the normal upper limit. The basal prolactin value was higher at the GA patients than at the PCO ones. The patients with PCO syndrome demonstrated significantly greater LH and prolactin elevation to the combined LH RH + TRH test than the patients with GA syndrome. On the basis of basal prolactin, estradiol and stimulated prolactin values it is likely, that the hyperprolactinemia in the two groups developed through different pathomechanisms. The persistent anovulation and the abnormal hormonal milieu in PCO syndrome cause the increased secretion of the pituitary lactotrophs supported by the TRH test, whereas the central dopamine decrease is the most likely explanation in the non tumourous GA cases. PMID- 3111127 TI - [Retrograde vascular catheterization as a differential diagnostic method of studying androgenization in the female]. AB - In 20 women with marked androgynism or testosterone concentrations being suspected for a tumor blood samples were taken by selective retrograde catheterization of the ovarian and suprarenal veins via vena femoralis. Testosterone, 17 beta-estradiol, and progesterone were determined and the concentration gradients to peripheral blood levels were calculated. In 20% of patients an pure adrenal and in 5% an ovarian hypersecretion of testosterone was established. A combined adrenal-ovarian hypersecretion was found in 50%. In 25% of the cases no final estimation was made because anatomic variations in venous size and drainage made catheterization and bilateral blood sampling impossible. There were no references to an androgen-secreting tumor. PMID- 3111128 TI - [Results of the GnRH-TRH and arginine-GnRH-TRH test in females with hyperprolactinemic galactorrhea]. AB - In 7 patients aged from 21 to 33 years (average age 24.6 years) with hyperprolactinemic galactorrhea a stimulation test with GnRH-TRH or arginine-GnRH TRH was performed. The serum levels of LH, FSH, PRL, HGH, TSH and total thyroxine (T4) were determined by RIA, the thyroxine binding capacity (TBC) by radio agent assay. The free thyroxine index (FT4-I) was calculated. An adenoma of the pituitary gland was diagnosed in 3 patients by X-ray of sella turcica. In all patients there were disturbances of the menstrual cycle. Independent of the existence of an adenoma of the pituitary gland in all patients with high basal levels. PRL could not have been shown stimulated by TRH. On the other hand it could be shown that despite of high basal PRL-levels in serum there was a normal stimulation of the gonadotrophs in 5 patients. Out of one patient the stimulation of the thyreotropic cells of pituitary by TRH was normal, too, whereas there was no or an inadaquate stimulation of HGH by arginine in all patients.--T4, TBC and FT4-I showed no deviation from the normal range. PMID- 3111129 TI - [GnRH-TRH and arg-GnRH-TRH test in females with normoprolactinemic galactorrhea]. AB - In 8 patients aged from 17 to 48 years (average age 32,6 years) with normoprolactinemic galactorrhea a stimulation test with GnRH-TRH or arginine-GnRH TRH was performed. The basal and stimulated serum levels of LH, FSH, PRL, TSH, HGH and total thyroxine (T4), the thyroxine binding capacity (TBC) and the free thyroxine index (FT4-I) were determined. -In a few cases there were disturbances of both the basal and the stimulated serum levels of the hormones. -Both the menstrual disorders which were seen in all patients with galactorrhea and the hormonal disturbances are discussed in context of an hypothetical increase of the PRL receptor sensibility in face of normal PRL serum levels or as a hint at a transient hyperprolactinemia. PMID- 3111130 TI - [Effect of the estrogen-progesterone combination preparations gravistat and Minisiston on carbohydrate metabolism]. AB - The effect of the estrogen-progesteron-combinations Gravistat (0.05 mg ethynylestradiol and 0.125 mg levonorgestrel) on glucose tolerance and plasma insulin was studied before and after tree and twelve months of treatment. In each case ten young fertile women participated in this study with aged 19 to 34 years. The fasting blood glucose and the glucose tolerance did not differ significantly under Gravistat and Minisiston. Reversible changes in the carbohydrate tolerance are most pronounced during the adaptations phase. The plasma insulin levels was no changed statistically under Gravistat and Minisiston. PMID- 3111131 TI - Represent the batches 2 of strain NCTC 3991 and NCTC 3992 B. coagulans? AB - In a previous publication (M. Hartung and E. Hellmann: Examination of 20 Bacillus Species by Crossed Immunoelectrophoresis under Taxonomic Aspects, Zbl. Bakt. Hyg. A 263 (1987) 509-524) we came to the conclusion that the species B. subtilis and B. coagulans were closely related. This statement has to be revised: The antigenic relationship is low. Further investigations have shown that all three B. coagulans-strains, although originating from different sources, were overgrown by B. subtilis. The same fact may have caused errors in other publications (e.g. Parry et al.: A Colour Atlas of Bacillus Species, Wolfe Medical Publications Ltd., London, 1983. PMID- 3111132 TI - Colicin Js of Shigella sonnei: classification of type colicin "7". AB - Colicinotype 7 of Shigella sonnei, introduced by Abbott and Graham, is one of those most frequently found in epidemiological screenings. It is represented by the production of a single colicin (acidic protein of m. w. 46 kD) endowed with some striking features. It is unstable at pH 8.0 and at the temperature of 70 degrees C. Its inhibitive activity is specific for the species Shigella sonnei, most strains of which seem to be sensitive. It is the only colicin known so far inactive towards Escherichia coli, including the indicator strains of broad spectrum sensitivity, such as K12 Row. It shows no cross-resistance with any other colicin type. Its adsorption on sensitive bacteria and inhibitive effect on them proceed extremely quickly. As indicated by indirect fluorimetry, its mode of action is extremely quickly. As indicated by indirect fluorimetry, its mode of action is probably different from those known for other colicins: it does not concern the plasma membrane of sensitive bacteria under aerobiosis, but it interferes with it under anaerobic conditions. These data show clearly that it is a unique colicin type. It is proposed to include it into the current system of classified colicins as "colicin Js". PMID- 3111133 TI - [The effect of magnesium on the formation of toxic shock syndrome toxin 1 (TSST 1) by Staphylococcus aureus]. AB - The influence of magnesium on the production of toxic shock syndrome toxin-1 (TSST-1) by Staphylococcus aureus was examined. As media we used: Standard-I Nutrient Broth, Todd Hewitt Broth, Mueller-Hinton Broth, Isosensitest Broth and a chemically defined liquid medium. The magnesium content of these media was determined using flame photometry and was subsequently changed using magnesium sulfate to the magnesium concentrations as shown in table 1. In each of these media the TSST-1 positive S. aureus strains MN8 and T 40 were grown at 37 degrees C, 18 h, vigorously shaken. Then the colony forming units (cfu) were determined. Toxin assays were performed by immunodiffusion after concentrating the culture fluids 100-fold using ethanol precipitation. Concentrations of toxin per milliliter were determined by comparison with standard toxin preparations using hyperimmune-TSST-1 antisera as described. The cfu and the amount of TSST-1 produced are shown in table 1. No link could be demonstrated between TSST-1 production and magnesium concentration of the media used. Our results are in agreement with the ones published by Schlievert and disagree with the results from Mills. PMID- 3111135 TI - Immunological properties and peptide mapping of two type I casein kinases from yeast. AB - Two protein kinases of Mr 43,000 and 23,000 from yeast, belonging to type-1 casein kinases, were purified to apparent homogeneity and used for investigation of their immunological affinity and for comparison of their peptide map patterns. The results obtained showed that antibodies against the 43 kDa kinase did not react with the 23 kDa enzyme. Moreover, the peptide maps of the radioiodinated kinases obtained either by chemical cleavage of peptide bonds in the presence of CNBr or by a limited digestion with V8 protease were completely different. All these observations point to the lack of relatedness between the two investigated enzymes. PMID- 3111134 TI - [A common meningococcaL intergroup antigen: immunological and immunochemical study]. AB - Protein-containing preparations forming 1 precipitation line in highly sensitive immunoelectrophoretic tests have been obtained from the culture fluid of meningococci, groups A, C and X. The preparations have been found to render a very high degree of protection to mice challenged with meningococci of the homologous serogroup and a sufficiently high degree of protection to those challenged with meningococci of the heterologous serogroups. After the repeated injection of the preparations the appearance of the booster effect has been registered. Immunochemical study has shown that the preparation is a stable complex consisting of protein, group-specific polysaccharide and a heat-resistant component common for serogroups A, C, X and Y. PMID- 3111136 TI - Pulmonary cytology in tuberculosis. AB - A review was made of 138 sputa, 4 bronchial washings and 4 bronchial aspirates from 64 patients with pulmonary tuberculosis. The cytologic findings that may indicate granulomatous involvement were epithelioid cells, giant cells, lymphocytes and a necrotic background. Cell-block preparations stained by the Ziehl-Neelsen technique gave a positivity for acid-fast bacilli similar to that of bacterioscopy. This study emphasizes the potential diagnostic value of inflammatory alterations, even when the main objective of pulmonary cytology is the diagnosis of neoplasia; the finding of epithelioid cells and giant cells in a necrotic background may indicate a specific granulomatous involvement. PMID- 3111137 TI - Systemic effects of 1,25-dihydroxyvitamin D3 on the pituitary-hypothalamic axis in rats. AB - Treatment of rats with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) 0.05 microgram/kg per day for three days was without any effect on serum T3, T4 or TSH concentrations, whereas serum PRL increased (20.6 +/- 3.8 to 76.2 +/- 19.1 micrograms/l, mean +/- SEM, N = 7-8; P less than 0.01). Increased hypothalamic TRH levels (24.3 +/- 3.9 to 45.7 +/- 7.8 pmol/g wet weight; P less than 0.01) may indicate an effect of 1,25(OH)2D3 on hypothalamic TRH homeostasis. This effect could probably be due to an indirect action of 1,25(OH)2D3, mediated by the increased serum calcium (2.77 +/- 0.02 to 3.16 +/- 0.08 mmol/l, mean +/- SEM, N = 7-8; P less than 0.001). This assumption was, however, not tested. Neither the pituitary TSH nor PRL was affected. The treatment decreased the serum concentration of 25-hydroxyvitamin D3 (23.0 +/- 1.3 to 16.8 +/- 2.0 nmol/l, mean +/- SEM, N = 5-7; P less than 0.01) and of 24,25-dihydroxyvitamin D3 (3.2 +/- 0.3 to 2.1 +/- 0.1 nmol/l, mean +/- SEM, N = 3-5; P less than 0.05). The results show that in this experimental design, 1,25(OH)2D3 has no effect on basal hormone secretion from the pituitary-thyroid axis, and that 1,25(OH)2D3 decreases the synthesis of the vitamin D3 metabolites studied. PMID- 3111139 TI - Successful treatment of a steroid-resistant form of idiopathic thrombocytopenic purpura in pregnancy with high doses of intravenous immunoglobulins. AB - Idiopathic thrombocytopenic purpura (ITP) during pregnancy may cause serious bleeding in the mother and fetus. Therapy with high-dose intravenous immunoglobulins has caused an immediate and predictable rise in platelet count in both adults and children with chronic or acute ITP. We report our experience in managing a woman near term in pregnancy. The patient demonstrated a rapid increase in platelet count, delivered without excessive bleeding and had a normal child with normal platelet count. Intravenous immunoglobulins may offer a new and safe way to control maternal and fetal platelet counts during pregnancy, delivery and neonatal period. PMID- 3111138 TI - Pharmacodynamics of [D-Ser (t-Bu)6,Des-Gly10]GnRH ethylamide (Buserelin) in 6 normal volunteers. Its usefulness to monitor treatment of central precocious puberty. AB - The disappearance rate of [D-Ser(t-bu)6,des-Gly10]GnRH ethylamide (Buserelin, HOE 766) was studied in plasma and urine after intranasal (300 micrograms) or sc (10 micrograms/kg) administration. A radioimmunoassay for HOE 766 was developed using 125I[D-Trp6,Des-Gly10]GnRH ethylamide as tracer and an antiserum raised against HOE 766. Cross-reaction with native GnRH was only 1.7%. Sensitivity was 1 pg/tube. In 6 male adolescents, the mean plasma HOE 766 concentration (+/- SEM) was 0.46 +/- 0.08, 0.50 +/- 0.10, 0.28 +/- 0.04, 0.24 +/- 0.04, 0.13 +/- 0.03, and 0.08 +/- 0.02 micrograms/l 30, 60, 90, 120 and 180 min after the intranasal administration, respectively. Concomitant urinary excretion of HOE 766-like material was 9.43 +/- 1.96 micrograms/4 h. There was a good correlation between integrated plasma levels and urinary excretion (r = 0.92). In the same 6 volunteers, the plasma HOE 766 levels were 21.2 +/- 3.0, 25.9 +/- 0.8, 21.2 +/- 0.9, 17.1 +/- 0.7, 12.8 +/- 1.1, 8.9 +/- 0.4, and 5.9 +/- 0.8 micrograms/l 20, 40, 60, 90, 120, 180 and 240 min after sc injection, respectively. The mean urinary excretion was 543 +/- 61 micrograms/4 h. In two girls with precocious puberty treated during 12 to 15 months with intranasal administration of HOE 766, urinary excretion of HOE 766-like material was shown to correlate well with the degree of inhibition of plasma 17 beta-E2 and of plasma LH and FSH responses to a GnRH challenge. Thus, monitoring of HOE 766 in urine appears to be helpful for evaluating of intranasal therapy with a GnRH analog in precocious puberty. PMID- 3111140 TI - Allogeneic bone marrow transplantation in multiple myeloma. AB - A 28-year-old woman with Bence-Jones multiple myeloma (MM) presented with several osteolytic lesions and a massive bone marrow infiltration with mature plasmocytes. After 6 cycles of chemotherapy with melphalan and prednisone, the patient, in apparent clinical remission, underwent allogeneic bone marrow transplantation (BMT) from her brother. The patient has been followed up for 23 months, showing complete remission by clinical and laboratory criteria. Other cases of MM treated with BMT and reported in the literature are reviewed and discussed. PMID- 3111141 TI - Chronic lymphocytic leukaemia complicated by recurrent Bell's palsy. AB - A patient who presented with a transient right-sided Bell's palsy (lower motor neurone lesion of the facial nerve) and chronic lymphocytic leukaemia (CLL) is described. During the following 5 years whilst receiving intermittent treatment for her CLL, the patient experienced two further episodes of Bell's palsy, one on the right side and the other left-sided. Each episode completely resolved. This is the first reported case of recurrent Bell's palsy complicating CLL. PMID- 3111142 TI - Analysis of cell proteins in lymphoblasts of acute lymphocytic leukemia by two dimensional gel electrophoresis. AB - The two-dimensional gel electrophoresis (2-DE) method developed by O'Farrell was used to analyze the differences of major proteins between lymphoblasts from children with acute lymphocytic leukemia (ALL) at diagnosis (lymphoblasts, n = 6), normal lymphocytes (n = 6) and lymphocytes from children with ALL in complete remission (lymphocytes in CR, n = 12). Among all the spots, those which were deeply stained and large were termed 'major spots'. Their number was 118. Two spots (No. B1 and B2) were characteristic of lymphoblasts, three spots (No. N1 N3) were characteristic of normal lymphocytes. In lymphocytes in CR, the latter spots were not always detected, and furthermore, the former spots were detected in several gels. These findings may relate to the insufficient recovery of functions of lymphocytes in CR. Several spots (No. 6, 55 and 57) in lymphoblasts were remarkably larger than those in normal lymphocytes. Spot No. 67, an actin spot, in lymphoblasts was smaller than that in normal lymphocytes. Spots No. 6, 55 and 57 in lymphocytes in CR were relatively small in size. PMID- 3111143 TI - Diagnostic and prognostic value of monoclonal antibodies in immunophenotyping of T cell lymphomas. AB - 6 cases of post-thymic T cell lymphoma (PTCL) and 4 cases of T lymphoblastic lymphoma were investigated with a panel of 21 monoclonal antibodies (MoAb). The PTCL group was composed of 2 by 2 cases of lymphoepithelioid cell lymphoma, T zone lymphoma and T immunoblastic lymphoma. In lymphoepithelioid cell lymphoma, the cell proliferating activity was low, and a malignant clone was not identifiable by the methods used. In the cases of T zone lymphoma and T immunoblastic lymphoma, malignant populations were detectable on the grounds of immunologic marker profile combined with cytologic particularities. The 4 cases of T lymphoblastic lymphoma were of a common cortical thymic phenotype (T4+, T8+, T6+) and presented with a mediastinal mass. In 3 of them, cell proliferation marker (Ki-67) was expressed by most tumor cells. Cell proliferating activity, however, did not inversely correlate with survival. PMID- 3111144 TI - Splenectomy in advanced chronic lymphocytic leukaemia. AB - A group of 20 patients with stage C chronic lymphocytic leukaemia (CLL) and marked splenomegaly refractory to anti-leukaemia treatment was evaluated in relation to clinical course and survival after splenectomy, and compared with a control group of non-splenectomised CLL patients at the same disease stage. Patients in the former group showed a significant clinical improvement after splenectomy, being reallocated to, and maintained in, stages A (85%) or B (10%) for more than 24 months. Ten patients were still alive 24-135 months after splenectomy. The 10 deaths observed in the group of splenectomised patients occurred 4-69 months after surgery, due to disease progression and/or immunoblastic transformation (4 cases), infectious complications (3 cases) and unrelated causes (3 cases). Analysis of survival from diagnosis showed a significantly better prognosis for patients in the splenectomised group (median survival 10 years, as compared to 3.5 years for the control group). The same statistical difference, p less than 0.001, with better life expectancy for splenectomised patients, was observed when the survival was calculated from the time of progression to stage C. These results strongly suggest a beneficial role for splenectomy in advanced CLL with significant splenomegaly, when the accumulation of resistant lymphoid cells precludes an adequate control of the disease by conventional forms of treatment. PMID- 3111145 TI - Phosphoglycolate synthesis by human erythrocyte pyruvate kinase. AB - R2-type pyruvate kinase purified monogeneously from human red cells catalyzes the phosphorylation of glycolate (glycolate kinase). Maximum activation of glycolate kinase was observed at 100 microM fructose-1,6-bisphosphate (Fru-1,6-P2) and at 2 mM glucose-1,6-bisphosphate (Glc-1,6-P2). The Km for ATP was 1.1 mM in the absence of Fru-1,6-P2 and 1.5 mM in the presence of 1 mM Fru-1,6-P2. The Km for glycolate was 20 mM in the absence of Fru-1,6-P2 and 5 mM in the presence of 1.0 mM Fru-1,6-P2. The optimum pH was over 10.5. At the physiological concentrations of Fru-1,6-P2, Glc-1,6-P2 and ATP, the glycolate kinase activity is too low to maintain the reported level of phosphoglycolate (approx. 2-5 microM). It is demonstrated that phosphorylation of glycolate by R2-type pyruvate kinase which is predominant in mature red cells plays no physiological role. The questions whether an unknown pathway for phosphoglycolate synthesis exists or whether there is actually phosphoglycolate in red cells are raised. PMID- 3111146 TI - Zinc and copper status in patients with sickle cell anemia. AB - Plasma zinc and copper concentrations were determined by atomic absorption spectroscopy in 57 patients with sickle cell anemia and in 45 control subjects from the Eastern Province of Saudi Arabia. Plasma zinc and copper levels in patients were found to be close to those of the control subjects. Similarly, there was a difference neither in urinary zinc level nor in the ratio Cu:Zn in patients and control subjects. This is in contrast to the situation which exists in North American Black subjects with sickle cell anemia, who are known to have zinc deficiency as well as a further decrease in zinc level during sickle cell crises. The near-normal levels of zinc and copper found in Saudi sickle cell patients therefore exclude zinc deficiency and confirm that this population exhibits a milder form of sickle cell anemia. PMID- 3111147 TI - Normal hematologic values and prevalence of anemia in children living on selected Pacific atolls. AB - The hematologic status of infants and children living on the small islands of the Pacific basin has been poorly documented. This report determines the normal ranges for hemoglobin (Hb) and mean corpuscular volume (MCV) for children residing on four of the small atolls of the Republic of the Marshall Islands in the archipelago of Micronesia. The difficulty in establishing normal hematologic values in pediatric populations is discussed and a methodology suggested that does not exclude any Hb value above the mean in determining the normal range for Hb. The study population was comprised of 563 Marshallese children representing approximately 3.4% of all children less than 16 years of age living in the Marshall Islands. The local prevalence of anemia and iron deficiency was also established. PMID- 3111148 TI - Digitonin cytochemistry reveals cholesterol-rich vesicles in uterine epithelial cells. AB - Freeze-fracture cytochemistry with digitonin has been used to examine the cholesterol content of the large apical vesicles of uterine epithelial cells. The vesicles are found to have cholesterol-rich membranes which supports the view that they are involved in cell secretion. We comment on the possible role of the vesicles in implantation. PMID- 3111149 TI - Optic nerve transection and tectal removal affect phagocytic activity of the pigment epithelium in goldfish. AB - The phagocytic ability of the pigment epithelium after optic nerve sectioning and tectal removal was investigated in the goldfish by the method of ingestion of latex beads. 4 days after sectioning, an increase in latex beads was evident which decreased by the end of the first week. Tectal removal also triggered increase intake of latex beads which was presented after 7 days. PMID- 3111150 TI - Histochemical research on metabolic pathways of glucose in some species of Mollusca Gastropoda. AB - The metabolic pathways of glucose were studied by histochemical reactions in some species of gastropods living in different habitats. The glycolytic pathway is histochemically indicated by positive results for glucose-6-phosphate isomerase, fructose-1,6-biphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase, and D-lactate dehydrogenase. The enzymes of the Krebs cycle gave different responses: isocitrate dehydrogenase and L-malate dehydrogenase were positive, whilst succinate dehydrogenase was constantly negative. Malate synthetase activity was also demonstrated. Despite L-glutamate dehydrogenase is undetectable, the presence of transaminase indicates the gluconeogenetic route. Phosphoglucomutase and glucose-6-phosphate phosphatase appear also positive. The metabolic meaning of our results were discussed. PMID- 3111151 TI - On the concanavalin A positive layer on the skeletal muscle fibre. AB - The localization and distribution of mannosyl and glucosyl residues on the extrajunctional sarcolemma of skeletal muscle fibres of frog, rat and new-born rat was studied by means of concanavalin A labelled with FITC and ferritin concanavalin A conjugate. A strong fluorescent layer surrounding the muscle fibres was found out. Ultrastructurally concanavalin A binding sites were established on the outer surface of muscle cell membrane, on the basal lamina, on the space between them, as well as on the reticular lamina, which ensheeted the muscle fibre. The width of the concanavalin A positive layer was 0.3 to 0.7 micron. On the basis of intensity of the fluorescence, some differences in the content of mannosyl and glycosyl residues during ontogeny as well between both species was admitted. PMID- 3111152 TI - Accuracy of an automated counting method by television-computer equipment in the quantitative autoradiography. AB - Commercially available television-computer equipment was used in the counting of silver grains in autoradiograms. The counting was made very rapidly and easily. The counts were compared with the counts made visually. With some limitations both counts showed excellent agreement. The accuracy of the method used is discussed. PMID- 3111153 TI - Endocytosis of horse-spleen ferritin by bony fish endocardium. AB - The endocytic uptake of horse-spleen ferritin by the endocardial cells in 2 bony fish species, Xiphophorus helleri and Pollachius virens, is described. In specimens of X. helleri injected intraperitoneally by a ferritin solution 1/10 h before the sacrifice, the endocardial bristle-coated vesicles, cytoplasmic tubules, and endosomes (smooth vesicles of variable size) contain a number of ferritin particles. These particles are taken up by the bristle-coated vesicles, transferred through the cytoplasmic tubules, and emptied into the endosomes. The latter get more tightly packed by ferritin and increase in size with the time elapsed between the injection and sacrifice. After 9 h, most ferritin-packed endosomes (4 to 6 micron) contain fragments of those inclusion bodies (0.5 to 1.5 micron) which normally occur in the teleostean endocardium, and are therefore regarded as lysosomes. The ferritin-rich lysosomes increase greatly in size with time and display a width of 6 to 12 micron after 28 h. The number of cytoplasmic tubules declines rapidly with time, whereas there is a constant production of new endosomes, which probably are derived from the former. The ferritin particles are not accumulated in the endothelium of the bulbus arteriosus, whereas the hepatic endothelial cells take up some small amounts of ferritin. A similar uptake of ferritin as described above was also observed in the heart of P. virens when perfused by a ferritin solution for 3 h. The present results are discussed and compared with those previously reported for the uptake of ferritin in various tissues in fishes and mammals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111154 TI - Bone embedding in pure methyl methacrylate at low temperature preserves enzyme activities. AB - Pure Methyl Methacrylate (MMA), a widely used embedding medium for undecalcified bone studies, was polymerized at low temperature (4 degrees C). MMA was prepared by a new purification procedure yielding a absolutely anhydrous and catalysed resin. The redox system benzoyle peroxide/NN-Dimethylanilin was used as the catalyzer-initiator system providing free radicals for the MMA chemical polymerization. Since the reaction is inhibited at -20 degrees C, complete infiltration of blocks is achieved within 3 d. Polymerization took place at +4 degrees C. The method provides undecalcified bone sections suitable for histomorphometric analysis of osteoid tissue, tetracycline bone labeling and Tartrate Resistant Acid Phosphatase. Enzyme histochemistry was shown to be possible in pure MMA embedded bones, when this low temperature embedding was used. PMID- 3111155 TI - Immunogold cell staining using monoclonal antibodies: application to lymphoid cells on coated slides. AB - The immunogold staining technique was presented for light microscopic detection of cell surface antigens with monoclonal antibodies. The lymphoid cells were adhered to glass slides precoated with the adhesive poly-(dimethyl-diallyl )ammonium chloride. The staining with the monoclonal mouse antibodies followed by the gold labelled sheep anti-mouse antibody was carried out on the cells adhered to the slides. In spite of the adherence, the patching of the gold marker as the prerequisite for the light microscopic detection occurred and the positively stained cells were visualized. On basis of this method the content of T lymphocytes (BL-T2+), B lymphocytes (BL-Ig-L/1+) and monocytes (BL-M/G+) in the mononuclear cell fraction of peripheral blood was determined in a population of healthy donors and of patients. The content of T lymphocytes of 29 healthy donors was determined using the immunogold staining technique (66.7 +/- 10.4%) and the immunofluorescence technique (67.6 +/- 9.5%). The correlation between the results obtained with both methods was highly significant (p less than 0.001). PMID- 3111156 TI - Gadolinium and didymium (praseodymium/neodymium) cations as capture agents in lightmicroscopical histochemistry of acid and alkaline phosphatase. AB - In previous papers, cerium and lanthanum based methods for light-microscopical detection of acid and alkaline phosphatase activity were proposed. In this paper, the usefulness of other lanthanide cations such as gadolinium and praseodymium/neodymium cations as capture agents in phosphatase histochemistry is tested. It is evident that phosphate ions were sufficiently trapped by these cations. According to the lead and silver multistep procedures earlier described it is possible to visualize alkaline phosphatase activity in the brush borders of the intestine or kidney as well as acid phosphatase activity in the lysosomes. These methods can be recommended. PMID- 3111157 TI - Immunohistochemical demonstration of neuron specific enolase (NSE) on cutaneous nerves: comparative study using NSE and S-100 protein antibodies on denervated skin. AB - The presence of neuron-specific enolase (NSE) and S-100 protein, which are nerve specific proteins, was immunohistochemically investigated on the cutaneous nerves. NSE was found in the axons of the cutaneous nerve bundles and the terminal axons in the Meissner and Pacinian corpuscles of the normal human and macaque skin. S-100 protein was found in the Schwann cells, lamellar cells of the Meissner corpuscles, and inner core cells of the Pacinian corpuscles. After denervation of the ulnar nerve on macaque, NSE on axons of the cutaneous nerves and Meissner and Pacinian corpuscles was completely disappeared in the 5th digit. However, S-100 protein was still maintained in the Schwann cells and Meissner and Pacinian corpuscles in the same digit. From these results, we conclude that the comparative immunohistochemical staining of NSE and S-100 protein is simple and reliable method to demonstrate the cutaneous nerves in normal and pathological conditions. PMID- 3111158 TI - Simple immunofluorescent method for identification of blood group in human tissues. II. Detection of A and B tissue isoantigens in paraffin sections. AB - An immunofluorescent method using diagnostic sera for blood groups A and B and FITC labelled antihuman globulin antisera was used for detection of A and B tissue isoantigens in routine formalin-paraffin sections. The method is simple and available for every histological laboratory. PMID- 3111159 TI - Simple devices for the preparation of specimens for scanning and transmission electron microscopy. AB - A simple and inexpensive equipment especially for the dehydration of cells grown on coverslips in a continuous linear gradient is described. On this way it is possible to handle many objects simultaneously. The coverslips, even irregularly formed, are fixed vertically in simple silicon-rubber-holders. The device including a described special holder can also be used for thorough rinsing of EM grids during the immunocytochemical labelling. PMID- 3111160 TI - Spinal neuroaxonal dystrophy and angioneuromatosis. AB - A man of 75 years of age had had lightning pains in the legs for 8 years. Clinical examination demonstrated mild pyramidal signs and involvement of the posterior columns. A morphine pump was placed in the epidural space in the lumbar region to treat the pain. He died two weeks later from a massive pulmonary embolism. The nervous system was examined using the classical techniques along with the use of poly- and monoclonal antibodies against nervous system specific proteins. The following features were demonstrated: neuroaxonal dystrophy of the posterior and anterior horns, and the posterior columns and corticospinal pathways in decreasing order of importance; angioneuromatosis of the grey matter of the lumbosacral spinal cord and loss of neurons of the dorsal spinal root ganglia and bilateral degeneration of the fasciculus gracilis. Previously, we have only found such amounts of spheroids in the spinal cord as measured here in cases of Seitelberger's disease. The angioneuromatosis was isolated and did not result from previous trauma nor was it associated with a known phacomatosis. This combination of features is very unusual and may explain the clinical features including the lightning pains. PMID- 3111161 TI - Acid maltase deficiency in the Japanese quail; early morphological event in skeletal muscle. AB - The skeletal muscle of Japanese quails with acid maltase deficiency (AMD) was studied morphologically at various developmental stages, from the 16th embryonal day up to 3 months after hatching. Membrane-bound glycogen particles began to appear in the affected skeletal muscle at the 16th embryonal day. In normal embryonic muscles, a certain amount of free glycogen particles was observed but they were not membrane-bound. Therefore, this is the earliest morphological event in the muscle of Japanese quails with AMD. In muscle at 3 weeks after hatching, the initial focal degeneration of myofibrils was recognizable but it was not associated with autophagic vacuoles. Quails with AMD developed muscle weakness and difficulty in lifting their wings at about 3 months after hatching: then numerous autophagic vacuoles were present. The formation of large autophagic vacuoles followed by fiber loss and fatty replacement seemed to contribute to the progressive muscle weakness. The study of Japanese quail with AMD will greatly facilitate the elucidation of the pathogenetic mechanism and is also a useful model for therapeutic trials in human AMD. PMID- 3111162 TI - Contribution of histiocytic cells to sarcomatous development of the gliosarcoma. An immunohistochemical study. AB - The expression of glial fibrillary acidic protein, fibronectin (FN), factor VIII related antigen (FVIII/RAG), and of three monohistiocytic markers, lysozyme, alpha-1-antitrypsin and alpha-1-antichymotrypsin was examined in five gliosarcomas (GS) by peroxidase-antiperoxidase immunostaining of formalin-fixed and paraffin-embedded specimens, and compared with vascular changes in 16 glioblastomas (GB). In contrast to GB, endothelial proliferations of GS were sheathed by sarcomatous tissue (perivascular sarcoma), which was contiguous with fibrosarcomatous areas. Cells with conspicuous intracytoplasmic FN content (FN+ cells) were seen in the vascular stroma of GB and dominated in the sarcomatous parts of GS. Most FN+ cells of GS were of varying size and shape and clearly neoplastic. Monohistiocytic markers were demonstrable in small infiltrating mononuclear cells as well as in many sarcomatous cells including FN+ cells. FVIII/RAG was restricted to lumen-lining endothelium and was not found in sarcomatous cells. These results suggest that a major part of sarcoma in GS is less likely to develop from proliferated endothelial cells than from histiocytic cells in the perivascular spaces of GB. By FN mediation, histiocytic cells might also guide and promote sarcomatous proliferations of other mesenchymal cells, leading to fibrosarcomatous development. Prominent monstrous giant cells of one GS seemed to be degenerating glioma cells. PMID- 3111163 TI - Single dose bromocriptine microcapsules in postpartum lactation inhibition. AB - The clinical efficacy and safety of a single intramuscular injection of Parlodel LA, Pravidel 50 mg, were studied in the prevention of lactation in 10 postpartum women. The overall efficacy at the end of the 28 day observation period was very good in 8 postpartum women and good in 2 women and no rebound lactation occurred. The prolactin plasma levels decreased to normal levels within 4 days in 9 women. Menstrual bleeding occurred in 9 women 4 to 6 weeks after treatment. Laboratory data recorded in this study support that Pravidel is effective in suppressing postpartum lactation. PMID- 3111165 TI - Spontaneous rupture of a diverticulum of the female urethra presenting with a fistula to the vagina. PMID- 3111164 TI - Fetal heart rate changes during diabetic ketosis. AB - A case of diabetic ketosis during pregnancy is presented in which the fetal heart rate tracing demonstrated tachycardia complicated by late and severe variable decelerations. Intravenous administration of insulin resulted in prompt abolition of the deceleration patterns. The implications of these findings are discussed. PMID- 3111166 TI - Stable glucose balance in premature infants with fluid restriction and early enteral feeding. AB - Hyperglycemia readily develops during intravenous glucose administration in premature infants. In this study glucose homeostasis was measured in 24 infants appropriate-for-gestational age with a gestational age between 27 and 34 weeks and a birthweight between 1,150 and 2,610 g. The infants were randomly assigned to one of two treatment groups. Fluid intake consisted of intravenous infusion of 5% glucose in Group 1 and 10% glucose in Group 2, and increasing amounts of human milk from the first day of life. The infants were treated in incubators with high air humidity in order to minimize insensible water loss and total fluid intake was restricted. The fluid restriction and early enteral feeding decreased the total amount of glucose given parenterally and thereby the risk of hyperglycemia. Glucose homeostasis was efficiently maintained in both groups and under the conditions described hydration by intravenous infusion of 5% and 10% glucose appear equally well tolerated. PMID- 3111167 TI - Rhesus immune globulin therapy following mismatched blood transfusion in a neonate. PMID- 3111168 TI - Growth hormone releasing hormone in the assessment and long-term treatment of growth hormone deficiency. AB - The secretion of hGH after the administration of the analogue of growth hormone releasing hormone, GHRH (1-29)NH2, to 8 normal adults and 41 short children has been studied. The children were classified on the basis of their hGH response to insulin-induced hypoglycaemia; 28 had severe hGH deficiency (peak serum hGH less than 7 mIU/litre) and 13 had simple short stature (peak serum hGH greater than 15 mIU/litre). The hGH response to GHRH was similar in normal adults and short stature children, but significantly lower in the hGH deficient children. In 23 (82%) of the hGH deficient children the peak serum hGH in response to GHRH was greater than 7 mIU/litre (the maximum value seen during hypoglycaemia), and in 14 (50%) the peak serum hGH in response to GHRH was greater than 15 mIU/litre. This suggests that in the majority of hGH deficient children the defect in hGH secretion results from hypothalamic GHRH deficiency. The hGH responses of the short stature children to insulin-induced hypoglycaemia were mainly in the low range of normal, and the majority showed normal hGH responses to GHRH. Eighteen prepubertal children with definite hGH deficiency have been treated for 3-18 months with twice daily, subcutaneous injections of GHRH. This has promoted linear growth in 12 children, of whom 8 showed an increment in height velocity of 2-11 cm/year. GHRH provides a valuable method for the assessment of hGH secretion, but by itself it cannot be used to establish deficient hGH secretion; this requires a stimulation test that promotes hypothalamic GHRH secretion, such as insulin-induced hypoglycaemia. GHRH is a practical alternative therapy to hGH for some hGH-deficient children. PMID- 3111169 TI - Growth hormone deficiency in adults--an indication for therapy? AB - Case studies are presented for two patients, one with isolated hGH deficiency and one with multiple hormone deficiencies. The patients were studied 3 months before, and 3 and 9 months after discontinuing hGH therapy, at 19 and 18 years of age, respectively. Strength in the quadriceps femoris, cross-sectional area of the quadriceps muscles and cross-sectional muscle fibre area were measured. In the patient with multiple hormone deficiencies, clear decreases in all three parameters were evident after discontinuing hGH treatment. There were no significant changes in the other patient. Reasons for these differences are discussed. PMID- 3111170 TI - Ultrastructural study of lymphocytic interaction with hepatocytes and endothelial cells in acute non-A, non-B hepatitis. AB - In the liver biopsy specimens of all six patients with acute non-A, non-B hepatitis, the lymphocytic interaction with hepatocytes and sinusoidal endothelial cells was observed by electron microscopic study. Lymphocytes were in a close contact with damaged hepatocytes and interrupted endothelial cells, and the microvilli on the surface of these damaged hepatocytes were degenerated and lost. These findings pointed out the possibility that the lymphocyte may play one of the important roles in hepatocytic damage and endothelial cell damage in acute non-A, non-B hepatitis. PMID- 3111172 TI - Isolation and functional activity of human blood monocytes after adherence to plastic surfaces: comparison of different detachment methods. AB - The recovery and purity of monocytes were assessed after adherence of human blood mononuclear cells to plastic surfaces, with subsequent detachment after exposure to EDTA, lidocaine, trypsin or low temperature (4 degrees C). No differences in purity were observed (81-90%) but the recovery was highest after treatment with lidocaine and trypsin. Pretreatment of the plastic surface with fetal calf serum increased the recovery to approximately 60%. The chemotactic response of the manipulated monocytes was decreased when trypsin had been used, compared with monocytes detached after exposure to low temperature, lidocaine or EDTA. In conclusion, for the measurement of chemotaxis the best results are obtained with monocytes after lidocaine detachment from a serum-pretreated plastic surface. PMID- 3111171 TI - Pineocytoma with neuronal differentiation demonstrated immunocytochemically. A case report. AB - Stereotactic biopsies were obtained from a tumor in the pineal gland of a 37 year old man. Histological and smear preparations were studied using conventional staining techniques as well as immunocytochemical methods with monoclonal antibodies to glial fibrillary acidic protein (GFAP), the neurofilament proteins (NFP), the presynaptic vesicle protein synaptophysin as well as with antisera to neuronal specific enolase (NSE). The tumor was classified as a pineocytoma. The tumor cells uniformly contained no cytoplasmic GFAP but NFP, NSE and synaptophysin as shown by the immunocytochemical techniques. The pineocytoma could thus be subclassified as a pineocytoma with neuronal differentiation. The patient subsequently succumbed due to a hemorrhage into the tumor and autopsy confirmed the biopsy findings. We conclude that immunocytochemical techniques may prove invaluable in the subclassification of tumors of the pineal region. PMID- 3111173 TI - Glomerulopressin activity in peripheral blood of newly diagnosed type I (insulin dependent) diabetic patients and in normal subjects treated with glucagon. AB - The glomerulopressin activity of the ultrafiltrate obtained from the peripheral blood of normal subjects, newly diagnosed Type I (insulin-dependent) diabetic patients (IDD), and in normal subjects treated with glucagon was studied in two bioassays: tonic tension contraction of the rat stomach fundus (TTC) and increase in the ureteral pressure of the toad, which was considered as a glomerular pressure index (delta GPI). The ultrafiltrate of four normal volunteers had a low activity in the TTC assay, and in two subjects no activity was observed. The ultrafiltrate of five of these subjects had no activity in delta GPI. In IDD patients the ultrafiltrates were active in the TTC assay and in the toad assay. In glucagon treated normal volunteers three of the ultrafiltrates were very active in the TTC assay and other three had a low activity. In the toad assay five of them were active and no response was observed in one subject. These observations suggest that glomerulopressin activity is increased in peripheral venous blood of untreated newly diagnosed IDD patients and in normal subjects treated with glucagon. PMID- 3111174 TI - Vitellin and vitellogenin characterization of Triatoma infestans and related species. AB - The vitellogenin-vitellin (VG-VN) of Triatoma infestans is a glycolipoprotein with a mol. wt. of 220,000; is a high density lipoprotein (1.18-1.21 g/ml) with low electrophoretic mobility at pH 8.2. There are many common proteins present in females, males, nymphs and eggs, but none is a glycolipoprotein. The major band of protein revealed a mol. wt. of 43,000, it is an anodic protein which appears in all the fractions of saline gradient. Males and females have a glycolipoprotein with electrophoretic mobility similar to VG-VN, but it is a low density lipoprotein. Another VG-VN, cathodic, not glycolipoproteic, is present in eggs and female hemolymph. The major VG-VN could be isolated from other proteins by ultracentrifugation in BrNa gradient or by DEAE-cellulose chromatography. Several species of Triatoma have immunological identity between theirs VG-VN. Female and eggs of Panstrongylus megistus and females, males and eggs of Rhodnius prolixus have a glycolipoprotein with partial immunological identity with the VG VN of Triatoma infestans. PMID- 3111175 TI - Brain monoamine metabolism is altered in rats following spontaneous, long distance running. AB - Brain monoamine metabolism in rats was studied during spontaneous, long-term running in a microprocessor-controlled wheel cage. Immediately after heavy spontaneous exercise, DOPA accumulation was decreased in dopamine-rich brain regions such as the limbic forebrain and corpus striatum, indicating a decreased rate of synthesis of dopamine in brain. In contrast, DOPA accumulation was increased in the noradrenaline-predominated region of the brain stem, indicating an increased synthesis of noradrenaline in this region. Alterations in brain monoamine metabolism were normalized in exercising animals analysed 24 h after the last running period. Changes in brain monoamine metabolism may be involved in the mechanisms underlying the clinically observed psychological effects of physical exercise. PMID- 3111177 TI - Reduced high density lipoproteins as a risk factor after acute myocardial infarction. AB - In a group of normocholesterolemic, non-diabetic middle-aged males surviving an acute myocardial infarction for 4 +/- 2 years (mean +/- SD), we have previously described a low apolipoprotein A-I and a deficient fibrinolytic activity as two major characteristics. In the present study we have followed morbidity and mortality risk factors for five years in these males. Mortality was 40% in a hypertensive group and 16% in a normotensive group. In the normotensive group mortality was related to reinfarction. Furthermore, patients with a poor prognosis in the normotensive group had lower high density lipoprotein (HDL) cholesterol and lower apolipoprotein A-I concentration in plasma than patients with a good prognosis. Unexpectedly, in the hypertensive group death was related to a low (p less than 0.05) cortisol concentration in urine. It is concluded that a low HDL level may be a bad prognostic sign in males who have sustained an acute myocardial infarction and show no evidence of other risk factors, such as diabetes, hypercholesterolemia or hypertension. PMID- 3111176 TI - Haemoglobin O2 binding in newborn and adult rabbits. AB - The relationship between haemoglobin O2 saturation and 2,3-diphosphoglycerate concentration (2,3-DPG) in haemoglobin solutions equilibrated with 3.7% O2-5.7% CO2 were identical in newborn and adult rabbits over a wide range of 2,3-DPG (0.5 40.0 mumol g-1 Hb), and independent of the haemoglobin concentration (1-10 g dl 1). Also, the resistance of the haemoglobin to alkali denaturation and the spectrophotometric absorption spectra of carboxy and oxyhaemoglobin between 500 nm and 650 nm, as well as the isoelectric focusing pattern of the haemoglobin after early and late stabilization with CO, were the same in newborn and adult animals. Both demonstrated one dominant band, focusing at pH 7.17, and one less conspicuous at pH 7.40. The erythrocyte pH was higher in the newborn than in the adult animals. Isoelectric focusing of erythrocyte pyruvate kinase demonstrated two isoenzyme bands in the newborn animals, one dominant fraction at pH 5.85 and one minor fraction at pH 7.97, whereas only the pH 7.97 band was observed in the adult. It is concluded that the physical properties of the haemoglobin molecule itself are the same in newborn and adult rabbits, and that the postnatal decrease in haemoglobin O2 affinity is solely due to changes in the erythrocyte metabolism, leading to a marked rise in 2,3-DPG and a minor decline in erythrocyte pH. The rise in 2,3-DPG is caused by decrease of pyruvate kinase, probably due to proteolytic inactivation of the enzyme. PMID- 3111179 TI - Autonomic and peripheral nerve function in early diabetic neuropathy. Possible influence of a novel aldose reductase inhibitor on autonomic function. AB - Autonomic and peripheral nerve functions as well as the possible short-term effect of a novel aldose reductase inhibitor (ARI) on neuropathy were evaluated in 30 male type I diabetics (age 25-44 years, mean 34; duration of diabetes 10-20 years, mean 34) with neurographic signs of peripheral neuropathy (PN). Autonomic neuropathy (AN) was established by the heart rate reactions to deep breathing (E/I ratio = vagal function) and to tilt (acceleration index = sympathetic and vagal functions; the brake index = vagal function). Twenty-nine patients, 13 with AN, completed the study. Among neurographic variables, only sural nerve function tests correlated with autonomic functions. Patients with AN showed significantly lower mean sensory action potential amplitudes (SAPA) sural, indicating axonal losses, than patients without AN (3.58 +/- 0.79 microV v. 7.34 +/- 1.12 microV; p less than 0.01). PN as measured by neurography did not improve during ARI treatment. On the other hand, vagal function (brake indices) improved (p less than 0.05) during ARI in AN patients. PMID- 3111180 TI - Familial dysalbuminemic hyperthyroxinemia. AB - A family with familial dysalbuminemic hyperthyroxinemia is described. The syndrome is inherited as an autosomal dominant trait and is characterized by marked elevation of serum thyroxine, due to increased binding of thyroxine to albumin, whereas serum triiodothyronine is normal. Serum free thyroxine is normal when measured with ultrafiltration or equilibrium dialysis, but artefactually high when measured with an analogue assay. The importance of the condition, which is harmless, lies in the misinterpretation of values with subsequent erroneous treatment of thyrotoxicosis. By using an ultrasensitive TSH method it is possible to discriminate between euthyroid and hyperthyroid patients and thereby to avoid incorrect diagnosis in subjects with euthyroid hyperthyroxinemia. PMID- 3111178 TI - Acute unidentified hepatitis in a hypogammaglobulinaemic patient on intravenous gammaglobulin successfully treated with interferon. AB - A 59-year-old male with acquired hypogammaglobulinaemia since 1978 developed a fulminant hepatitis. The hepatitis appeared after two years intravenous treatment with Sandoglobulin (Sandoz, Switzerland). No virus markers could be detected in the body fluids or liver tissue. Blood transfusions had not been given within one year before development of the liver disease. There was strong suspicion that the patient had acquired non-A non-B hepatitis from the gammaglobulin infusions. Treatment with alpha-interferon ran parallel to a normalization of the pathological liver enzymes and the histology of the liver. This observation suggests a direct antiviral effect of alpha-interferon, despite the anecdotical and noncontrolled character of these data. PMID- 3111181 TI - Olfactory epithelium of marine fishes in scanning electron microscopy. AB - The olfactory organs of six teleost fish species were studied using scanning electron microscopy. Differences were found in number and arrangement of lamellae in the olfactory rosette, and five types of arrangement were distinguished. Four types of arrangement of sensory and indifferent epithelium were established in rosettes of the species studied. Differences in organization of the sensory epithelium in teleost fish species are seen in quantitative relationships of different receptor and secretory cells. In teleost fish, flagellar receptor cells were most numerous. In the sensory epithelium of flounder, separate flagellae distinguishable from ordinary flagella of receptor and supporting cells by their large size and membrane structure, were described. Secretory cells were observed in sensory and indifferent epithelium as dark openings which often occurred in marine teleosts, mediosmatics. In some species (greenling, sea bullhead), the openings look like wide craters and may be stomata of secretory ducts of the epithelial olfactory glands described earlier. PMID- 3111182 TI - Aortic endothelial and smooth muscle cell interactions in culture. AB - The effect of conditioned media on cell growth was studied in pig aortic smooth muscle cell conditioned medium on pig or bovine aortic endothelial cells and pig or bovine endothelial cells conditioned medium on pig aortic smooth muscle cell proliferation. Co-culturing experiments were also done in the same combinations. Cell proliferation was measured in both systems by 3H-thymidine incorporation autoradiography. In intraspecies combinations the media conditioned by confluent pig-aortic endothelial monolayer had an inhibitory effect on pig-aortic smooth muscle cell growth, but in the co-cultivation system the exponentially grown endothelial cells stimulated smooth muscle cell proliferation. The pig aortic smooth muscle cells had some stimulatory effect on pig endothelial cell proliferation in both systems. In the interspecies combination the media conditioned by confluent bovine aortic endothelial monolayer or, in the co cultivation experiments, the bovine endothelial cells exerted a stimulatory effect on the proliferation of pig-aortic smooth muscle cells. The media conditioned by pig smooth muscle cells had also some little stimulatory effect on bovine aortic endothelial cell growth, but in the co-cultivation system the bovine aortic endothelial cells responded in a highly sensitive way to the stimulatory effect of pig aortic smooth muscle cells. PMID- 3111183 TI - Electron microscopy of macrophages obtained from bronchial lavage-fluid. AB - The ultrastructure of pulmonary alveolar macrophages (PAM) was studied in smokers, non-smokers, and in patients with alveolar proteinosis, Boeck sarcoidosis and heavy-metal coniosis. Cells were collected from therapeutic or diagnostic bronchial lavage-fluid. Typical alterations are reported for each disease studied. Diagnostic bronchial lavage has opened new perspectives in pulmonology. However, the study of the cellular constituents of the lavage requires in addition to morphology, biochemical and immunological techniques. The most frequently occurring cell type of the bronchial lavage is alveolar macrophage (AM, AMA, PAM). In the intact lung its number amounts to 15 X 10(9). These cells are 12-20 microns in diameter and when stained with Giemsa, dark blue cytoplasmic granules and cytoplasmic vacuoles are seen. They are PAS-positive and contain a negligible amount of lipids. Cytochemistry has shown several enzymes in PAM. With transmission electron microscopy a polymorphic, excentric nucleus and single membrane-bound cytoplasmic inclusions were demonstrated. The surface properties of PAM were studied by scanning electron microscopy. The aim of the present study was to give account of electron microscopic findings in therapeutic and diagnostic bronchial lavage. PMID- 3111184 TI - Overlapping imprinting of thyrotropic (TSH) and gonadotropic (FSH, LH) hormones in cultures of newborn rat testicles and ovaries. AB - Cultured gonadal cells of male and female newborn rats increase their hormone binding capacity after the first treatment with gonadotropin. The imprinting effect of thyrotropin, similar in structure to gonadotropin and binding to its receptors, was found more pronounced in testicular than in ovarial cells. In the latter a negative imprinting with TSH was observed. Results corroborate the view that hormone receptors are present in early stages of ontogenesis and prove the development of imprinting also in cultured target cells. PMID- 3111185 TI - Quantitative morphological and histochemical study of the xiphisternal cartilage and its intracellular lipids in the guinea-pig. AB - The xiphisternal cartilages of newborn, suckling, immature and adult guinea-pigs were divided into twelve regions in a study of their histology and intracellular lipid content. Histochemical methods were employed, and the observations quantified using a semi-automatic image analyser. In general, triglyceride content increases with age and is lower in surface layers and in distal and lateral regions than in deep layers and proximal and medial regions. Phospholipids, on the other hand, diminish with age and are most abundant in surface layers and in distal and lateral regions. The nature and quantity of these lipids in the various regions and layers into which the cartilages were subdivided has been related to the size of the lacunae in which the cells lie. PMID- 3111186 TI - Axonal regeneration following retrochiasmatic deafferentation in young and adult rats. AB - Regeneration of nerve fibres after hypothalamic knife cuts was studied by the anterograde transport of horseradish peroxidase [HRP] in female rats of various ages. Retrochiasmatic frontal cuts were made in 2, 5, 7 and 11-day-old and in adult rats. Four, 6, 7 and 12 months later HRP was injected rostral to the cut line in the suprachiasmatic area. HRP-stained nerve fibres ran rostro-caudally from the injection site through the cut-line in animals operated upon at 2, 5 and 7 days of age. In contrast to the former group, animals operated on the 11th day of life as well as in adult rats no HRP-stained nerve fibres could be seen passing through the cut-line which was marked by scar formation. In one animal operated in adulthood a bundle of nerve fibres noticed 7 months after the surgery turned medially at the caudal end of the cut-line and spread over the frontally deafferented area. The character of these newly formed fibres was different: part of them showed a varicose appearance, the others exhibited even contours. The present findings indicate that the deafferented [or isolated] hypothalamus remains neuronally isolated from the environment if the operation is carried out later than the end of the first week of life. Operations made during the first postnatal week do not leave permanent traits in the brain. PMID- 3111187 TI - Electron microscopic demonstration of viruses and bacteria in cardiac myocytes from victims of sudden cardiac death. AB - In 7 men and 1 woman who died suddenly the functionally important areas of myocardium in the sino-auricular area and the subendocardial layers of left ventricle were obtained by necropsy no more than 3 h after death, and then prepared for study by electron microscopy. In three cases of five, in whom the cause of death was cardiovascular insufficiency, viral particles and bacteria were identified. In three other cases of sudden non-cardiac death they were not found. Viruses were found only in working cardiomyocytes, but near the sinus node. Bacteria were found in left ventricular subendocardium. Intercellular junctions between virus-damaged myocytes and intact cells were preserved. Based upon the functionally important sites where they were found, associated degeneration near them, and preservation of contacts among myocardial cells there, viruses and bacterial infections may play an important role in the patho physiologic events leading to some cases of sudden death. PMID- 3111188 TI - The importance of endothelial cells in the course of vascular surgical interventions. AB - Aorto-coronary bypass made by implanting the patient's own saphenous vein may exhibit a tendency to early and late occlusion. This phenomenon is influenced by a number of factors including intraoperative damages of the graft. To determine preferable techniques for preserving vein integrity, various human graft preparation techniques were compared. Endothelial damage may occur during the preparation of the saphenous vein; the extent of damage depends on the preparation technique. In our studies the endothelium was best preserved by Rheomacrodex filling at 100 water cm pressure. Early occlusion seems to be best avoided in certain conditions using Gore-tex (polytetrafluoro-ethylene) prostheses due to the fact that the structure of Gore-tex simulates the normal endothelium covering of the luminal surface of the vessels and renders quick "re" endothelialization. This may reduce the hazard of early graft occlusion. In the present study experimental models and grafts implanted in humans were compared and results were tested by scanning electron microscopy. PMID- 3111189 TI - Self-retaining brain retractor pressure during intracranial procedures. AB - One hundred and twenty recordings of the pressure beneath self-retaining brain retractors were obtained in 23 patients who were fully alert preoperatively. The brain retractor pressure (BRP) recordings showed a characteristic shape of the curves with an initial steep and later a more gradual slope. The BRP at the tip was higher than at the center of the retractor. The BRP recordings varied considerably as well in pressure (0-75 mmHg) as in time (4-40 minutes). Changes in systemic blood pressure and BRP in the 23 patients did not reduce the regional cerebral perfusion pressure (rCPP) below 10 mmHg for more than six to eight minutes, except in six cases. In five of the six patients an infarction demonstrated by CT scan developed beneath the area of application of the retractors. Only two patients later demonstrated clinical signs of cerebral infarction. Induced hypotension with sodium nitroprusside and the administration of mannitol did not influence the current pressure beneath the brain retractors. PMID- 3111190 TI - Cavernomas of the central nervous system: clinical syndromes, CT scan diagnosis, and prognosis after surgical treatment in 25 cases. AB - We present our clinical experience and the results of surgical management with 25 cavernomas of the CNS, treated in our hospital in the last 10 years. The location of the lesion assessed by clinical and CT scan examinations, proved to be the most significative factor determining the prognosis of cavernomas of the CNS, after surgical removal. The symptoms started in most of the cases in the third decade of life. 19 cases were located in the cerebral hemispheres and produced three well defined clinical syndromes: Irritative syndrome (seizures) present in 70% of the cases. Space-occupying lesion syndrome (20%) and haemorrhagic syndrome (10%). The remaining six cases were located within the basal ganglia, brainstem, pineal region, cerebellum and spinal cord, showing a progressive course. CT scan studies were performed on 24 cases. The characteristic image of a cavernoma is represented by a moderately hyperdense nodule with discreet contrast uptake. Calcification was observed in and around the lesions in 33% of the cases. Perilesional hypodensities suggestive of brain tissue atrophy were noted in 22% of the CT scans. On the other hand, 12% of cerebral hemisphere cavernomas showed atypical CT scan images that suggested an erroneous diagnosis of cystic gliomas. Radical surgical removal was performed in all cases. The postoperative results varied according to the location of the lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111191 TI - Graded spike electrogenesis in mouse pancreatic beta-cells. PMID- 3111192 TI - TRH-induced TSH and prolactin responses in the elderly. AB - Since there are divergencies in the thyrotropin (TSH) response to thyrotropin releasing hormone (TRH) in old age, and since a hypothalamopituitary dysfunction has been suggested in the elderly, we have studied the thyroid function and the TRH responsiveness of TSH and prolactin (PRL) in 56 euthyroid patients over 70 years old, grouped according to age (70-79, 80-89, 90 or more years) and sex. Results were compared to those of 15 postmenopausal women and 11 men. In the elderly patients there was a decrease in plasma tri-iodothyronine (T3) and an increase in reverse T3 (rT3) levels while thyroxine (T4), basal TSH and PRL levels remained normal. The mean TSH and PRL responses to TRH (250 micrograms i.v.) were reduced but there was no age effect within the elderly. Only a sex effect was detected, TSH and PRL responses being appreciably lowered in men. In eight patients without severe disease or malnutrition, the response of TSH was not significant. We conclude that despite an apparent euthyroid status, TSH and PRL responses are blunted in elderly patients, and more in men than in women. These data, consistent with a hypothetical hypothalamopituitary dysfunction, indicate the difficulties of thyroid status assessment in the elderly. PMID- 3111193 TI - Histamine levels and activity of histidine decarboxylase (HD) and histamine methyltransferase (HMT) in neonate and adult human brain. AB - The adult human brain contained histamine (HI), and showed well-expressed histidine decarboxylase (HD), histamine-methyltransferase (HMT) and monoamine oxidase (MAO) activity. The neonate human brain contained HI, and showed HMT and MAO activity; there was no HD activity. Neither the adult nor neonate brains possessed diamine oxidase activity. PMID- 3111194 TI - Inhibition of intestinal diamine oxidase by detergents: a problem for drug formulations with water insoluble agents applied by the intravenous route? AB - One hundred and twenty four water-insoluble drugs were included in a study for their action on diamine oxidase (DAO) after solubilization with 61 detergents. 16 detergents were themselves not water-soluble and were not further investigated. A further 3 detergents affected the extraction procedure and 7 of the remaining 42 detergents themselves inhibited the activity of canine intestinal DAO in vitro. Only 5 detergents fulfilled all prerequisites for our DAO assay, including the solubilization of 76 water-insoluble drugs. Each of these 5 detergents had an individual range of suitability in our test system. 3/76 drugs inhibited DAO in concentrations up to 10(-3) M. This result is in contrast to our study with water soluble substances, where 16% were DAO inhibitors. Since detergents can block the enzyme which is responsible for histamine catabolism, some of the observed adverse reactions to drugs could arise because of the presence of such detergents in the formulation. PMID- 3111195 TI - Elevation of the large bowel histamine concentration by aminoguanidine induced diamine oxidase inhibition. AB - In inflammatory diseases of the large bowel a reduced diamine oxidase activity was found which may be related to a reduced oxidative degradation of histamine. An experimental inhibition of diamine oxidase could therefore influence the large bowel histamine concentration. The diamine oxidase inhibitor aminoguanidine was administered to rats in a single dose of 100 mg/kg orally, i.v., or i.p. A rapid increase of the concentration of the drug in the large bowel was measured (half life = 2-5 h). During chronic amino-guanidine administration (3 times/week, 100 mg/kg orally) the large bowel histamine increased by 30% on average. This may be sufficient for a proliferative stimulus of the intestinal mucosa. Previous reports of an increase of body weight of animals and of patients under aminoguanidine treatment could not be confirmed by our study. PMID- 3111196 TI - Diamine oxidase (DAO) activity and intestinal mucosa integrity: influence of suture techniques. AB - After various kinds of intestinal mucosal injuries, whether by disease or by experiment, the diamine oxidase activity is reduced. Therefore, we studied the effect of surgical manipulations on the intestinal mucosa and diamine oxidase activity. The reaction of the gut on the insertion of sutures was a transient increase of the enzymic activity followed by reduction as soon as the mucosa started to gain weight. After a standardized pressure injury only a reduction of the diamine oxidase activity together with an enhancement of the mass of the intestinal wall was found. A hypothesis of a feed-back regulation of the diamine oxidase activity connected with mucosal proliferation is proposed. PMID- 3111197 TI - Stimulation of histamine synthesis from tumour cells by concanavalin A and A23187. AB - In the present study the amount of histamine synthesized by two experimental tumour cell lines, the Yoshida ascites sarcoma cells and SEWA cells, was measured after stimulation in vitro with the calcium ionophore A23187 and the plant lectin Concanavalin A (Con A). After 7 hrs of incubation with the two stimulators, histamine could be measured and the amount was still increasing up to 15 hrs of incubation with a maximal net histamine production of approximately 1.0 ng histamine per 10(6) tumour cells per ml sample. In addition, the tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was found to enhance the synthesis of histamine in the presence of Con A or A23187, except in high concentrations, i.e. 50 ng/ml TPA, where an inhibitory effect was seen. TPA alone could not induce detectable histamine synthesis. In order to measure the histamine, the tumour cells were incubated in glass microfibre-based microtiter plates, which have been shown to bind histamine with high affinity and selectivity. The aim has been to develop a functional in vitro tumour assay which can detect histamine from tumour cells and which can be used to measure pharmacological interaction of the tumour cell function as well as histamine production from different tumour cell types. PMID- 3111198 TI - Causal relationship between a tumour growth and the changes in histamine metabolism in tissues of sarcoma-bearing rat. AB - The relationship between malignancy and histamine metabolism in the liver and the small intestine has been examined in sarcoma-bearing Wistar rats two weeks after subcutaneous implantation of a transplantable methylcholanthrene sarcoma Sa1828 and on the 3, 7 and 14th days after tumour extirpation. Two weeks after tumour implantation, the histamine level was increased by 100% and 50% in the liver and the small intestine, respectively. On the 3rd day after extirpation of the tumour the level of histamine had returned to the control values and remained unchanged during the next 10 days. Neither of the histamine catabolizing enzymes, diamine oxidase with a putrescine as a substrate or histamine methyltransferase were influenced by the existing tumour or by its extirpation except on the 14th day where a high increase in diamine oxidase activity was found. Some changes in the distribution of histamine metabolites suggest an involvement of an oxidative pathway of histamine catabolism as well as the aldehyde catabolizing enzymes in tumour development. PMID- 3111199 TI - [Prevention of experimental diabetic corneal endotheliopathy with aldose reductase inhibitor]. PMID- 3111200 TI - [Prevention of rat galactose cataract with topical aldose reductase inhibitor, E 1008]. PMID- 3111201 TI - Enigmatic cyst-forming sporozoon in the spinal cord of a dog. PMID- 3111202 TI - ASNR: the silver anniversary. Neuroradiology: the next 25 years. PMID- 3111203 TI - MR of brain radiation injury: experimental studies in cats. AB - Two of six cats receiving small-field, single-dose, brain irradiation of 35 Gy with 6 MeV photons developed brain abnormalities in the irradiated area on MR images at 6 and 8 months, respectively, after treatment. The lesions were of high intensity on T2-weighted images and did not enhance after IV administration of gadolinium-DTPA. An additional lesion in one of these cats displayed high signal on T2-weighted images and enhanced on T1-weighted images after IV gadolinium DTPA. Pathologic correlation revealed that the nonenhancing T2-weighted lesions consisted of edema or demyelinated regions without inflammation while the gadolinium-enhanced lesion demonstrated necrosis with inflammatory infiltrate. Focal brain irradiation may produce noninflammatory demyelination and necrosis. These histologic entities may be potentially distinguished on MR with IV gadolinium-DTPA. PMID- 3111204 TI - Surface coil MR imaging of orbital blowout fractures: a comparison with reformatted CT. AB - Four patients with orbital blowout fractures were evaluated by surface coil MR imaging, and the resulting images were compared with computer reformatted CT scans. The surface coil afforded significant improvement in spatial resolution, resulting in better demonstration of the blowout fracture. Surface coil MR was found superior to CT in the assessment of fracture site, extent of prolapsed orbital fat, and muscle entrapment. PMID- 3111205 TI - Type I schizencephaly: CT and neuropathologic findings. AB - Type I schizencephaly, which is less commonly recognized than the type II variety, consists of a "fused" cleft in the cerebral mantle. Its CT appearance is significantly different from the type II variety, and it may be confused with postdevelopmentally acquired lesions. The CT appearance of eight cases (seven girls and one boy, aged 10 months to 18 years) of type I schizencephaly was correlated with clinical findings and previously recorded neuropathologic features. Presenting symptoms included developmental delay, seizures, and hemiparesis. CT findings in each case showed a unilateral, cortically lined cleft in the parasylvian region extending from the hemispheric surface to the ventricle. Micropolygyria was present in the cortex lining the cleft, and in two of eight patients was also visible elsewhere in the cerebral cortex. Those with associated microcephaly (four of eight patients) had significantly more severe neurologic deficits than did those without microcephaly. CT findings in type I schizencephaly are characteristic and show excellent correlation with neuropathologic specimens. The appearance of these lesions can be explained on the basis of a disorder of neuronal migration in early gestation and they should not be confused with postdevelopmentally acquired lesions. PMID- 3111206 TI - A cliniconeuroradiologic approach to third cranial nerve palsies. AB - Sixty-three patients with third cranial nerve palsies (CNPs), either isolated (31) or in association with other neurologic deficits (32), underwent neuroophthalmologic and neuroradiologic evaluation. Discrepancies between the clinical and radiologic evaluations were analyzed and useful clinical presenting symptoms were identified. Microvascular infarction secondary to diabetes mellitus and/or hypertension was the most common cause in patients with isolated third CNP, and extensive neuroradiologic evaluation is not indicated in this subgroup. The overall diagnostic yield of high-resolution CT for isolated third CNPs was low (30%), but improved to 60% if diabetes and hypertension were excluded. However, CT was highly sensitive (90%) in those patients with third CNPs associated with additional neurologic deficits. The status of the pupil in and of itself cannot be the sole determinant as to whether angiography is indicated to exclude an aneurysm. Careful ophthalmologic observation and relating the severity of pupillomotor dysfunction to extraocular ophthalmoplegia is mandatory to determine the logical sequence of radiologic evaluation. Retroorbital pain taken in isolation is a nonspecific presenting symptom and has differential diagnostic value only if it is correlated temporally with the onset of third CNP and the presence or absence of additional cranial nerve deficits. PMID- 3111207 TI - The interventricular extension of choroid plexus papillomas. AB - Four cases of choroid plexus papilloma extending through the foramen of Monro are presented. All four patients were evaluated by contrast-enhanced CT and two of these were also evaluated by neurosonography. No other intraventricular tumor commonly extends through a ventricular outlet. The radiographic demonstration of this extension of an intraventricular mass through the foramen of Monro, cerebral aqueduct, or foramen of Luschka or Magendie represents an ancillary diagnostic sign of choroid plexus papilloma. PMID- 3111208 TI - The "keyhole": a sign of herniation of a trapped fourth ventricle and other posterior fossa cysts. AB - When a cystic structure in the posterior fossa increases in size, the accompanying increase in pressure may cause it to herniate upward through the tentorial hiatus. In our experience this happens most commonly with a dilated trapped fourth ventricle secondary to infection or intraventricular hemorrhage. However, herniation of an arachnoid cyst or a Dandy-Walker malformation through the tentorium may also occur. When herniation occurs, the cystic structure assumes a "keyhole" configuration, indicating that it is trapped and that surgical intervention is necessary. Five cases are presented that illustrate this point, including two patients with dilatation of the fourth ventricle secondary to hemorrhage, two patients with Dandy-Walker malformation, and one patient with an arachnoid cyst. PMID- 3111209 TI - The radiology of the pterygoid canal: normal and pathologic findings. AB - To better define the normal anatomy and pathologic features of the pterygoid canal, 100 normal subjects and 38 patients with disease of the paranasal sinuses, nasopharynx, and base of the skull were studied with pluridirectional tomography. Particular attention was given to the normal radiographic appearance of the pterygoid canal as well as to its anatomic variants and its relationship to the paranasal sinuses. Three radiographic signs of involvement of the pterygoid canal were detected: disappearance, enlargement, and narrowing. Moreover, a brief correlation between pluridirectional tomography and CT was made. Diagnostic accuracy in evaluating the bony lesions is the same with both techniques, but CT is superior to pluridirectional tomography in evaluating involvement of the soft tissues. PMID- 3111210 TI - The significance of internal carotid artery occlusion shown by i.v. digital subtraction angiography. AB - A retrospective review of 493 IV digital subtraction angiography examinations performed for cervicocerebral vascular disease revealed 27 apparent occlusions of the internal carotid artery. We identified 20 patients whose occlusions did not warrant further investigation. Fourteen occlusions were on the asymptomatic side, two were in patients who preferred medical treatment, two were in patients unsuitable for carotid endarterectomy, and two patients with bihemispheric transient ischemic attacks were treated for the contralateral carotid. Four very tight stenoses were found in the other seven patients, one of whom refused endarterectomy. As the signs of a very tight stenosis are subtle, and the number of such stenoses that are treatable is low (three in 493), cerebral angiography is justified in doubtful cases to avoid missing potentially treatable lesions. PMID- 3111211 TI - CT anatomy of the craniovertebral junction in infants and children. AB - Computed tomographic (GE 9800) images of 129 patients (from newborn to 18 years old) with no evidence of cervical spine pathology were reviewed retrospectively from available material to evaluate normal anatomic appearances in childhood. The synchondroses may appear solid at soft-tissue window settings, while, with appropriate bone-window settings, a lucent line will be seen. Residual lucency and then (generally) sclerosis were seen at synchondroses past the age of classic anatomic fusion. A transversely oriented groove on the undersurfaces of the occipital condyles was imaged in children ages 5-12 years. This groove is described radiologically in that age range for the first time in this report. The development of the ossification centers of C1 was illustrated with CT. The two vertically oriented, rod-shaped ossification centers of the lower dens develop a bilobed appearance in axial section when they begin to fuse. An apparent deficiency of the cortex seen posteriorly in this area (in children as old as 7 years) represents the last remnant of the cleft between the dens centers. The cord was always outlined distinctly by CSF at soft-tissue settings at the foramen magnum and C1 levels without intrathecal or IV contrast enhancement. This anatomic feature is particularly useful since it enables the evaluation of the spinal canal in this region in some cases (especially craniovertebral junction anomalies) without the need for intrathecal contrast materials. PMID- 3111212 TI - Vertebral artery trauma: transcatheter embolization. AB - Injuries of the vertebral arteries in four patients were treated by transcatheter embolization. Embolotherapy was performed after incomplete or unsuccessful surgery in three of the patients and as a preventive measure in lieu of surgery in the fourth patient. All procedures were successful and without complications. An injured vertebral artery is usually extremely difficult to approach surgically, but because of extensive collateral blood supply it is usually expendable; therefore, it becomes an inviting target for management by interventional angiographic techniques. Embolotherapy of an injured vertebral artery is easier, faster, and safer than its surgical ligation and, therefore, decidedly superior. With few exceptions, embolotherapy should be considered the preferred method in the management of vertebral artery trauma. PMID- 3111213 TI - Glutaraldehyde cross-linked collagen (GAX): a new material for therapeutic embolization. AB - In a search for a better agent for use in therapeutic embolization, a newly available bovine collagen product, glutaraldehyde cross-linked collagen (GAX), was evaluated to determine its effectiveness in causing arterial obstruction, its persistence after embolization, and the acute and chronic pulmonary toxicity resulting from direct pulmonary embolization. GAX is an effective agent for causing arterial obstruction: 3-4 ml caused prompt flow arrest when injected into the internal iliac artery of six dogs. In this canine model, the material persisted within embolized tissue for as long as 2 months, and at follow-up intervals of 2 days, 2 weeks, and 2 months, its presence did not produce any cellular response. Studies of both acute and chronic pulmonary toxicity reveal that when GAX is embolized directly into the pulmonary circulation it causes adverse effects only by mechanical blockage of pulmonary arteries. GAX offers several advantages over other currently available agents and is of sufficient safety that clinical trials in humans can be undertaken. PMID- 3111214 TI - MR imaging of spinal dysraphism. AB - Spinal dysraphism includes anomalies of midline fusion involving bony, mesenchymal, and neural elements. MR imaging of the spine was performed as the initial imaging technique to determine its role in the evaluation of 31 children when spinal dysraphism was clinically suspected or when radiographs revealed errors of ossification of the posterior elements (spina bifida). Correlation of surgical findings in 17 of 18 abnormal examinations and metrizamide myelography with CT in six of these cases indicated that accurate diagnosis was provided by MR in all instances. Examples of spina bifida aperta (spina bifida cystica)- including myelomeningocele, myelocystocele, and lipomyelomeningocele--and those of occult spinal dysraphism--such as dorsal dermal sinus, spinal lipoma, and tight filum terminale (thickened filum)--are presented. These cases show MR to be a reliable technique in the initial evaluation of these disorders. PMID- 3111215 TI - MR imaging of syringohydromyelia and Chiari malformations in myelomeningocele patients with scoliosis. AB - The brain and spinal cord were examined with MR imaging in 30 myelomeningocele patients 3-32 years old to study the prevalence of syringohydromyelia and Chiari malformations and to correlate these conditions with developmental scoliosis and spontaneously arrested hydrocephalus. Twelve patients had neurologic deficits above the level of the myelomeningocele and 10 had spontaneously arrested hydrocephalus. MR visualized syringohydromyelia in four patients with widened or focally bulging spinal cords and in eight patients with atrophic spinal cords. All patients had Chiari malformations, 28 of type II and two of type I. Syringohydromyelia was not correlated with type of scoliosis, result of ventriculoperitoneal shunting procedures, radiologic level of the myelomeningocele, or extent of the Chiari malformation. The two patients with the most rapid progression of thoracic scoliosis had the most extensive syringohydromyelia and radiologically low lumbar levels. Neurologic deterioration due to syringohydromyelia and Chiari malformations is probably more common in myelomeningocele than has been recognized previously and may cause developmental scoliosis, loss of ambulation, impaired extremity function, and progressive cranial nerve paralysis. PMID- 3111216 TI - Neuroimaging and the lesion of multiple sclerosis. AB - In a patient with long-standing multiple sclerosis (MS), a double-dose delayed contrast-enhanced CT scan obtained during exacerbation revealed many areas of enhancement. Vigorous treatment with corticotropic hormone was followed by almost complete disappearance of these abnormalities. No areas of low attenuation were seen on a later unenhanced CT scan. Finally, MR imaging showed only a single area compatible with a plaque of MS. It is suggested that pathologic alteration of the blood-brain barrier seen in MS is not necessarily followed by demyelination and plaque formation. Restoration of the integrity of the blood-brain barrier may thus possibly prevent the formation of plaques in some MS patients, in particular if this can be accomplished early in the course of the exacerbation. PMID- 3111217 TI - Carcinomatous encephalitis: CT and MR findings. PMID- 3111218 TI - Oculocerebrorenal syndrome: case report with CT and MR correlates. PMID- 3111219 TI - Isolated cerebral mucormycosis: case report with CT and pathologic correlation. PMID- 3111220 TI - A dural spinal arteriovenous malformation with epidural venous drainage: a case report. PMID- 3111222 TI - Unusual patterns of solitary sacral plasmacytoma. PMID- 3111221 TI - Paranasal sinus involvement in thalassemia major: CT demonstration. PMID- 3111223 TI - CT myelography of subarachnoid leukemic infiltration of the lumbar thecal sac and lumbar nerve roots. PMID- 3111224 TI - MR of hemorrhage. PMID- 3111225 TI - Risk of ferromagnetic ocular foreign bodies in MR. PMID- 3111227 TI - Use of coils for transcatheter carotid occlusion. PMID- 3111226 TI - Pantopaque on MR. PMID- 3111228 TI - Cervicocephalic fibromuscular dysplasia and fenestration of the vertebral artery. PMID- 3111229 TI - CT of inspissated mucus in chronic sinusitis. PMID- 3111230 TI - CT of acute cervical tendinitis. PMID- 3111231 TI - Central pontine myelinolysis: report of a case with distinctive appearance on MR imaging. PMID- 3111232 TI - MR demonstration of falx ossification: recognition and differential diagnosis. PMID- 3111233 TI - MR in evolution: applications of new technology. PMID- 3111234 TI - Surgical neuroangiography: search for a speciality. PMID- 3111235 TI - Viral hepatitis and international travel. AB - Hepatitis A is widely encountered during international travel. Risk varies with duration of travel, adherence to usual tourist routes and frequency of endemic disease. Prophylaxis with immune globulin is effective and has particular indications. Although travelers are not generally considered to be at risk of hepatitis B unless they have sexual contact with the indigenous population, the risk may be greater than was previously estimated. PMID- 3111236 TI - Chronic flecainide therapy selected by electrophysiology testing of intravenous flecainide. AB - The utility of flecainide acetate was evaluated in 93 patients by means of electrophysiologic studies before and after intravenous flecainide administration to determine long-term efficacy. Twenty patients had a prior history of at least one cardiac arrest and 73 patients had sustained ventricular tachycardia (VT). The mean radionuclear ejection fraction was 32 +/- 5%. Flecainide was evaluated in 93 patients, with 44 patients no longer having VT following flecainide (47% efficacy). Procainamide was evaluated in 69 patients; 24 patients had an adverse reaction to reaction to procainamide and 28 of the 69 patients were protected on procainamide (40% efficacy). The mean serum concentration of flecainide achieved in the protected group was 298 +/- 36 ng/ml and 4.3 micrograms/ml for procainamide. Both flecainide and procainamide significantly prolonged refractoriness, lengthened QRS duration, while only procainamide increased the QT interval. All 93 patients were discharged on antiarrhythmic therapy, 42 on flecainide, 27 on other antiarrhythmic therapy guided by electrophysiologic testing, and 24 on amiodarone (when all other agents failed). Six of the 42 patients on flecainide complained of adverse side effects, but none were severe enough to warrant stopping therapy. Of the 42 patients on flecainide, four (9%) died suddenly over 18 +/- 4 months. Twenty-seven patients were on other therapy; eight of these have died, three suddenly (11%), four with myocardial infarctions, and one due to congestive heart failure. Twenty-four patients started amiodarone; 11 have died, five (21%) suddenly, four of congestive heart failure, one of pulmonary fibrosis, and one with myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111237 TI - Electrophysiologic and antiarrhythmic effects of oral encainide in patients with atrioventricular nodal reentry or nodoventricular reentry. AB - Three patients with drug-resistant atrioventricular (AV) nodal reentrant tachycardia and two patients with reciprocating tachycardia associated with nodoventricular pathways received oral encainide after a control drug-free electrophysiologic study. In one patient with AV nodal reentry, encainide prolonged anterograde AV nodal conduction, produced complete ventriculoatrial (VA) block, and prevented tachycardia induction. Encainide had no effect on AV or VA conduction in the second patient with AV nodal reentry, and tachycardia with similar cycle length was still induced. The third patient was not studied while receiving encainide, but spontaneous AV nodal reentrant tachycardia occurring multiple times daily was abolished. In both patients with nodoventricular pathways, anterograde AV nodal and VA conduction were prolonged by encainide and tachycardia was no longer inducible. Two patients with AV nodal reentry were given long-term encainide therapy and have been free of recurrent arrhythmias for 16 and 30 months. One patient with a nodoventricular pathway has been without arrhythmia recurrence after 73 months of encainide therapy; the other patient required addition of propranolol to encainide because of recurrent tachycardia. We conclude that encainide can prolong anterograde AV nodal and VA conduction and prevent induced and spontaneous tachycardia in some patients with drug-resistant and highly symptomatic AV nodal or nodoventricular reentry. PMID- 3111238 TI - Double-blind randomized comparison of intravenous tocainide versus lidocaine in the treatment of chronic ventricular arrhythmias. AB - The efficacy and safety of intravenous tocainide were compared with intravenous lidocaine in patients with chronic ventricular arrhythmias in a double-blind, parallel study. Twenty-nine patients were randomized to a tocainide (n = 15) or lidocaine (n = 14) group. Antiarrhythmic efficacy was defined as a greater than or equal to 50% reduction in single ventricular premature complex (VPC) frequency, greater than or equal to 90% reduction in paired VPC frequency, and total abolition of ventricular tachycardia. Efficacy was observed in 40% (6 of 15) of patients in the tocainide group and in 36% (5 of 14) patients in the lidocaine group. A 75% or greater reduction in total VPCs occurred in 40% (6 of 15) of patients in the tocainide group and in 57% (8 of 14) of patients in the lidocaine group. Greater than 90% suppression of paired VPCs occurred in 9 of 13 (69%) patients taking tocainide and in 6 of 11 (54%) patients taking lidocaine. Total abolition of ventricular tachycardia was documented in 5 of 11 (45%) patients given tocainide and in two of six (33%) patients given lidocaine. A total of 17 adverse reactions affecting 86% (12 of 14) of patients taking lidocaine and 11 adverse reactions affecting 53% (8 of 15) of patients taking tocainide occurred. Four patients in each treatment group suffered dose-limiting adverse effects. This study suggests that the efficacy and safety of intravenous tocainide are similar to that of intravenous lidocaine in patients with chronic ventricular arrhythmias. PMID- 3111239 TI - Coronary arteriography in the intact rabbit: demonstration of coronary vasomotor and electrocardiographic effects of ergonovine and indomethacin in rabbits after abrupt cessation of prolonged nitroglycerin treatment. AB - Abrupt withdrawal of chronic nitroglycerin treatment may predispose the coronary circulation to spasm. To test this hypothesis directly, we developed a technique for performing selective coronary arteriography in the intact rabbit with images obtained by video-based methods or cineangiographic film. Experiments were then conducted in rabbits treated three times daily with topical nitroglycerin ointment for 6 weeks and in age- and sex-matched control animals. Forty hours after cessation of treatment, animals were anesthetized, and ECG and coronary vasoactive effects (determined by coronary arteriography) of ergonovine, 0.2 mg/kg (intravenous) and indomethacin, 25 mg/kg (intravenous) were assessed. Of six nitroglycerin-treated rabbits, one died of ventricular fibrillation prior to arteriographic study. The remaining five developed ECG abnormalities (single ventricular premature beats, nonsustained ventricular tachycardia, and ST segment deviation) upon challenge with ergonovine or indomethacin. Neither agent evoked ECG changes in control rabbits. In contrast, the degree of luminal diameter reduction in epicardial coronary arteries provoked by ergonovine or indomethacin did not differ between control and nitroglycerin-treated animals. Focal coronary artery spasm was not observed in any rabbit. Our results demonstrate that selective coronary arteriography in rabbits is feasible and that changes in vessel caliber may be assessed from images thus obtained. Data from this study indicate that ergonovine- and indomethacin-induced ECG abnormalities observed in nitroglycerin-treated rabbits cannot be ascribed to epicardial coronary artery spasm. PMID- 3111240 TI - Ketogenic effects of low and high levels of carnitine during total parenteral nutrition in the rat. AB - Male Wistar rats received total parenteral alimentation for 3 d. The animals were divided into three groups: group 1, without L-carnitine; group 2, 10 mg (62.1 mumol) L-carnitine X kg-1 X d-1; and group 3, 100 mg (621.1 mumol) L-carnitine X kg-1 X d-1. Fat oxidation was followed by indirect calorimetry. Maximal oxidative metabolism of fatty acids was achieved with supplementation of L-carnitine in small amounts (10 mg X kg-1 X d-1). This was demonstrated by a decrease of the RQ and of the serum concentrations of fatty acids and by an increase of beta-OH butyric acid. Decreased liver free and long-chain acylcarnitine and increased short-chain acylcarnitine concentrations in this group also demonstrate an increased ketogenicity. This ketogenic effect of carnitine decreases when higher concentrations of carnitine are used. This study demonstrates that the ketogenic effect of carnitine is dose dependent. PMID- 3111241 TI - Medium for the simultaneous detection of pyocyanin and fluorescein pigments of Pseudomonas aeruginosa. AB - To help simplify the identification of Pseudomonas aeruginosa by clinical microbiology laboratories, the authors developed a new medium, pyocyanin fluorescein agar (PFA), which enhances the production of both Pseudomonas pigments simultaneously. Production of pigments on PFA was equivalent to production on a pyocyanin agar (P agar) and a fluorescein agar (F agar) used in combination and was superior to either P agar or F agar used alone. The medium is simple to prepare and it detected pigment in 94% of P. aeruginosa isolates tested. PMID- 3111242 TI - Empirical paternity exclusion rates. AB - We have developed an empirical method of estimating paternity exclusion rates for any genetic system by counting exclusions among fictitious "nonfather" paternity cases generated from true paternity disputes. Especially for multiallele multiloci systems, this technique has advantages over traditional formulae methods in that it replaces tedious (and, in some cases, impossible) computations with simple data file manipulations, and it avoids introducing quantities such as gametic disequilibrium and recombination fraction that are difficult to measure. Exclusion rates for standard and one-parent paternity cases are given for three racial groups (Caucasians, blacks, and Hispanics) in four genetic systems (HLA, ABO, MNSs, and Rh). Beside the method, of interest are our findings of higher HLA exclusion rates (93.25% for Caucasians, 94.62% for blacks, and 95.82% for Hispanics) compared with rates previously reported and high combined exclusion rates (89.59% for Caucasians, 91.65% for blacks, and 92.54% for Hispanics) in one parent paternity cases. PMID- 3111243 TI - Does oral enzyme replacement therapy reverse intestinal lactose malabsorption? AB - The effects of oral enzyme replacement therapy on breath hydrogen excretion and symptoms after milk ingestion were studied in lactase-deficient patients. Sixteen symptomatic patients underwent interval hydrogen breath tests using whole milk as substrate. Each study was repeated with the addition of 250 mg of beta-D galactosidase derived from Aspergillus oryzae (Lactrase) given orally with the milk. Subsequently seven of those 11 patients who did not normalize their hydrogen excretion with 250 mg of Lactrase were available to be restudied with a 500-mg dose. Mean cumulative and peak hydrogen excretions were calculated for the baseline (milk alone), 250 mg, and 500 mg Lactrase groups. Significant (p less than or equal to 0.05) decreases in cumulative and peak hydrogen excretion were noted between the 500 mg Lactrase versus the baseline group, but not between the 250 mg versus baseline group. Five of the 16 (31%) symptomatic lactase-deficient patients normalized their hydrogen excretion after 250 mg of Lactrase; four of seven (57%) who had not normalized on 250 mg, normalized their hydrogen excretion with 500 mg of Lactrase. A different pattern was observed in the incidence of symptoms. Five of the nine patients (56%) whose hydrogen excretion normalized with the addition of Lactrase at either dosage became asymptomatic after milk ingestion; in addition, three patients who did not normalize their hydrogen also became asymptomatic. We conclude that oral Lactrase in sufficient dosage temporarily reverses lactose malabsorption in some patients. PMID- 3111244 TI - Pyoderma gangrenosum associated with ulcerative colitis: treatment with disodium cromoglycate. AB - Pyoderma gangrenosum is an uncommon skin disorder that is associated with ulcerative colitis, Crohn's disease, polyarthritis, and other conditions. Clinically it is usually characterized by painful ulceration of the skin and subcutaneous tissues, predominantly of the lower limbs. Treatment is empirical and often unsatisfactory. We report two cases of pyoderma gangrenosum associated with inflammatory bowel disease successfully treated with topical disodium cromoglycate. PMID- 3111245 TI - Percutaneous endoscopic gastrostomy tube deterioration: how common is the problem? PMID- 3111246 TI - Gastric diverticulum invaded by gastric adenocarcinoma. PMID- 3111247 TI - Hermansky-Pudlak platelets: further studies on release reaction and protein phosphorylations. AB - Platelets from a patient with the Hermansky-Pudlak syndrome were studied. These platelets had decreased amounts of serotonin and adenine nucleotides, and a decreased number of mepacrine-labeled dense bodies. beta-Thromboglobulin and acid hydrolases contained in alpha-granules and lysosomes respectively were present in normal amount. Platelets in platelet-rich plasma did not respond to collagen, but arachidonic acid and ionophore A 23187 induced normal aggregation and normal thromboxane (TX) synthesis. Alpha-granule release was found impaired and remained subnormal even with high doses of inducers. In response to thrombin aggregation, release and TX synthesis of isolated metrizamide gradient platelets were found at lower than normal levels. Phosphorylation of P20 and P43 proteins was normal. Only a combination of ADP plus thrombin could restore a normal aggregation, with normal alpha-granule and lysosome release and normal TX synthesis. These results indicated that in the absence of dense bodies: the release of other granules is impaired; the TX synthesis is delayed except when induced by arachidonic acid and A 23187 ionophore; the absence of dense bodies could be compensated for by the addition of ADP which restores the impaired release reaction and TX formation; and P20 and P43 polypeptides were phosphorylated as rapidly as those in normal platelets. PMID- 3111249 TI - Concomitant occurrence of disseminated intravascular coagulation and factor VIII inhibitor in a patient with prostatic cancer. AB - An 86-year-old man, diagnosed as having carcinoma of the prostate, stage D, was admitted to the hospital. Soon after admission, he developed bleeding from various sites, including intravenous puncture sites and gastrointestinal and urinary tracts. A clinical diagnosis of disseminated intravascular coagulation (DIC) was made, which was corroborated by laboratory data. A factor VIII inhibitor of 12.5 Bethesda units was also identified in the patient's plasma. Concomitant occurrence of disseminated intravascular coagulation and an acquired factor VIII inhibitor has not been reported previously. PMID- 3111248 TI - Maturation of B-lineage blast crisis cells in chronic myeloid leukemia. AB - A 44 year-old Chinese male presented with lymphoid blast crisis of chronic myeloid leukemia, in which the blast cells exhibited a pre-pre-B cell phenotype (B4+B1-J5+12+smIg-). There was a phenotypic transition during the course of the disease to a more mature B cell phenotype (B4+B1+J5+12+smIgG lambda+). The maturation of blast crisis cells may be related to the chemotherapeutic agents used in the treatment of the disease. PMID- 3111250 TI - Peripheral blood remission of hairy cell leukemia after transfusion hepatitis. AB - Hairy cell leukemia is a chronic lymphoproliferative disorder characterized clinically by splenomegaly and cytopenias. Spontaneous remissions are rare and splenectomy is often performed when the blood counts worsen and cause symptoms. Three of our patients with hairy cell leukemia developed recurrent pancytopenia and transfusion-dependent anemia after splenectomy. Each subsequently acquired transfusion hepatitis and in two patients marked hematologic improvement was noted within 2 months. Complete peripheral blood remission occurred within 17 months in all patients although bone marrow infiltration with hairy cells persisted. One patient remains in remission for 12 years; the other two succumbed to infectious illnesses but with normal blood counts. The mechanism by which hepatitis virus induces hematologic recovery in patients with hairy cell leukemia is unknown but may involve augmentation of the interferon system. PMID- 3111251 TI - Involvement of von Willebrand factor in thrombosis following asparaginase prednisone-vincristine therapy for leukemia. AB - To determine if factor VIII-von Willebrand factor (vWF) complex is involved in the thrombosis associated with asparaginase-prednisone-vincristine induction therapy for acute lymphoblastic leukemia, plasma vWF was analyzed by sodium dodecyl sulfate-agarose gel electrophoresis and crossed immunoelectrophoresis. Five patients with cerebral thrombosis were studied; all had a decreased platelet count following the complication. Sequential studies of three patients disclosed changes in plasma vWF multimer pattern. One patient who was studied serially from 2 days before to 1 day after the event, had an increase in unusually large plasma vWF multimers that disappeared after the complication. The other two patients who were studied at presentation subsequently showed a decrease in plasma large vWF multimers, especially remarkable in the patient having the sharpest decrease in platelet count. No appreciable difference in vWF multimer pattern, when compared to normal pooled plasma, was found in the remaining two patients who were only studied at presentation, or in the seven controls who received the same treatment but did not develop thrombosis. Crossed immunoelectrophoretic analyses of two patients tested disclosed a right shift of immunoprecipitin line in one and a left shift in the other. Our findings suggest that the thrombotic complications resulted from platelet agglutination by plasma vWF. PMID- 3111252 TI - Should platelets be radiolabelled in plasma medium? AB - Because of the low labelling efficiency of platelets with In-111 oxine in plasma containing media, most investigators have labelled platelets in plasma-free media. However, labelling of platelets with In-111 oxine in plasma-free media may result in either: irreversible damage leading to rapid clearance from the circulation and permanent hepatic sequestration; or reversible damage with transient hepatic sequestration without affecting the in vivo survival. Since human platelets can be labelled with In-111 oxine in plasma in sufficient efficiency for routine clinical use, they should be labelled in plasma whenever possible. The use of newer In-111 chelates, tropolone and mercaptopyridine-N oxide, which label platelets with high efficiency in plasma as well as in plasma free media, may offer another alternative. PMID- 3111253 TI - Management of myeloma kidney: an anti-light-chain approach. AB - This report describes the course of 23 patients with multiple myeloma and severe renal failure treated with a combination of plasmapheresis, chemotherapy, and supportive measures. Eight of ten patients with acute renal failure (ARF) obtained recovery of renal function, and in five of them serum creatinine concentration returned to normal. The remaining two patients died before the effect of treatment could be evaluated. Eleven of 13 patients with chronic renal failure (CRF) had substantial, albeit incomplete, improvement in renal function. The extent of functional recovery appeared to depend on the type of renal lesions, probably related to the duration of exposure to light chains. The median survival of the whole series of patients was 9 months, and five patients lived longer than 3 years. No clear-cut difference in survival was found between the group with ARF and that with CRF, although the latter presented higher values of serum creatinine at the time of diagnosis and residual renal insufficiency after the completion of treatment. Moreover, no significantly different survival times were found when the group with complete recovery of renal function was compared to that with minor improvement. Thus, renal failure, with the availability of effective forms of treatment of uremia, did not play a major prognostic role in our series. In contrast, the response to chemotherapy appeared to be the outstanding factor conditioning the duration of survival in these patients. PMID- 3111254 TI - Determining the equivalence of transdermal nitroglycerin products. PMID- 3111256 TI - Multiple myeloma presenting with primary meningococcal arthritis. AB - A 64-year-old white man presented with Neisseria meningitidis primary septic arthritis. Further evaluation revealed multiple myeloma. Increased susceptibility to infection occurs early in multiple myeloma; thus, a rare cause of primary septic arthritis, such as N. meningitidis, warrants a full evaluation for immunocompromise. PMID- 3111255 TI - Moderate hypocalcemia due to normal serum 1,25-dihydroxyvitamin D levels in an asymptomatic kindred with familial hypoparathyroidism. AB - Hypoparathyroidism was diagnosed in nine members of a kindred of three generations. This study investigated why these persons were asymptomatic and without developmental abnormalities, in contrast to the common presentation of idiopathic hypoparathyroidism. In the hypocalcemic subjects, serum calcium level was 7.4 +/- 0.8 mg/dl (mean +/- SD) and ionized serum calcium level was 3.48 +/- 0.21 mg/dl. Immunoreactive parathyroid hormone values were inappropriately low. Injection of EDTA in one patient lowered ionized calcium levels, but immunoreactive parathyroid hormone values did not rise. Serum levels of 1,25 dihydroxyvitamin D and other vitamin D metabolites were normal or elevated and substantially higher than in other hypoparathyroid states. The normally observed positive correlation between the fasting urinary calcium/creatinine ratio and serum 1,25-dihydroxyvitamin D that reflects the dependence of net bone resorption on 1,25-dihydroxyvitamin D was upheld in hypoparathyroid patients. It is proposed that the subjects with familial hypoparathyroidism in this kindred had moderate asymptomatic hypocalcemia without developmental abnormalities because normal or elevated serum 1,25-dihydroxyvitamin D levels enhanced intestinal calcium absorption. This may represent one point in the spectrum of idiopathic hypoparathyroidism. Alternately, both the moderate degree of hypocalcemia and the normal serum calcitriol values could have been related to mild, partial hypoparathyroidism, which could have been inherited in this kindred. PMID- 3111257 TI - Norfloxacin, a fluoroquinolone antibacterial agent. Classification, mechanism of action, and in vitro activity. AB - Norfloxacin is an orally absorbed fluoroquinolone antibacterial with a fluorine at position 6 and a piperazine ring at position 7. These changes have resulted in a marked enhancement (compared with that of the older quinolones) of in vitro antibacterial activity. Specifically, the antibacterial spectrum of norfloxacin includes Pseudomonas aeruginosa, as well as enteric pathogens. Norfloxacin is also active against both penicillin-susceptible and penicillin-resistant strains of Neisseria gonorrhoeae. Relative to its activity against gram-negative bacteria, norfloxacin is somewhat less active against gram-positive cocci. In general, the staphylococci are more susceptible to the drug than are the streptococci. As with all fluoroquinolones, norfloxacin's activity against anaerobic bacteria is poor. For urinary tract bacterial isolates, the following Bauer-Kirby disk diffusion zone-size breakpoints have been proposed: greater than or equal to 17 mm, susceptible; 13 to 16 mm, intermediate; less than or equal to 12 mm, resistant. Bacteria with minimal inhibitory concentrations (MICs) less than or equal to 16 micrograms/ml are considered susceptible; those with MICs greater than or equal to 32 micrograms/ml are considered resistant to norfloxacin. The mechanism of action of norfloxacin involves inhibition of the A subunit of the important bacterial enzyme DNA gyrase, which is essential for DNA replication. Plasmid-mediated resistance to the fluoroquinolones is not encountered. Further, although some cross-resistance within the fluoroquinolone class has occurred, there is little cross-resistance between norfloxacin and antibiotics of other classes. PMID- 3111258 TI - Primary idiopathic hypothalamic hypothyroidism. Report of four cases. AB - One man and three women with hypothalamic hypothyroidism are described; they had isolated thyrotropin-releasing hormone deficiency, otherwise normal pituitary function, and no identifiable central nervous system anatomic abnormality. Serum thyrotropin levels were low and thyrotropic response to thyrotropin-releasing hormone was uniformly present, consistent with a hypothalamic cause of hypothyroidism. In two patients, hypothyroidism was transient and spontaneously resolved; in one of them, it was recurrent. Because hypothalamic hypothyroidism is mild and potentially reversible, it is suggested that such patients have follow-up evaluation before therapy is initiated in order to avoid unnecessary treatment. PMID- 3111259 TI - Respiratory muscle weakness and ventilatory failure in AL amyloidosis with muscular pseudohypertrophy. AB - Generalized muscle weakness culminating in ventilatory failure developed in a 59 year-old man with kappa light chain multiple myeloma. Physical examination demonstrated skeletal muscle enlargement, severe proximal muscle weakness, and macroglossia, consistent with amyloid-associated muscle pseudohypertrophy. Pulmonary function studies revealed a severe restrictive abnormality with a low maximal inspiratory pressure and maximal voluntary ventilation. Arterial blood gas values and chest radiographic results were normal. There was no clinical evidence of cardiac or central nervous system disease. At autopsy, skeletal muscles and diaphragm were diffusely infiltrated by amyloid. There was also multifocal deposition of amyloid in alveolar septae, esophagus, and subendocardium. This report suggests that ventilatory failure may occur as a complication of myeloma-associated (AL) amyloidosis involving the respiratory muscles. PMID- 3111260 TI - Inherited thyroxine-binding globulin excess and thyroiditis. PMID- 3111261 TI - Monoclonal hypergammaglobulinemia without malignant transformation in angioimmunoblastic lymphadenopathy with dysproteinemia. PMID- 3111262 TI - Common fragile sites: their prevalence in subjects with constitutional and acquired chromosomal instability. AB - Chromosomal fragile sites that are inducible by methotrexate and aphidicolin are frequent in the human population. To assess the frequency and distribution of these common fragile sites, we performed a cytogenetic survey on lymphocytes from subjects known to be particularly prone to breakage because of constitutional chromosomal instability, the possession of a rare fragile site, or Fanconi anemia. Furthermore, a group of cancer patients was included in this study in view of possible acquired chromosomal instability. Lymphocyte chromosomes from several healthy donors were analyzed under identical conditions. We found that methotrexate- and aphidicolin-induced fragile sites are widespread in the general population, showing a similar breakpoint distribution. Ten fragile sites (3p14, 16q23, 2q32, 6q25, 4p16, 4q31, 14q24, 1p31, 20p12, 7q21) were observed in at least 40% of the individuals among the different groups. Our data point out a significantly increased breakage induced by aphidicolin in lymphocytes from cancer patients and, to a lesser extent, from rare fragile sites carriers. These results suggest that common fragile sites are enhanced in some constitutional and acquired conditions. PMID- 3111263 TI - Cyclooxygenase inhibition reduces placental transfer: reversal by carbacyclin. AB - The effect of the cyclooxygenase inhibitors, indomethacin and ibuprofen, on diffusional transfer in the human placenta was assessed with the dual-perfused isolated placental lobe. Antipyrine, a freely diffusible substance, was used as an indicator of placental transfer efficiency. Each inhibitor (100 mumol/L) was perfused for 30 minutes after a baseline period, resulting in a significant reduction in antipyrine clearance. During a subsequent washout period, ibuprofen inhibited antipyrine clearance returned to baseline values, whereas indomethacin inhibited clearance remained reduced. An additional 30 minutes perfusion of 500 mumol/L of ibuprofen resulted in a further reduction in antipyrine clearance compared with 100 mumol/L of ibuprofen, suggesting a dosage-related effect. The perfusion of each inhibitor caused a reduced production of 6-keto-prostaglandin F1 alpha (the stable metabolite of prostacyclin) in the fetal circulation. The simultaneous perfusion of carbacyclin, a prostacyclin analogue, at 100 nmol/L and 1 mumol/L resulted in a dosage-dependent reversal of the effects of ibuprofen (500 mumol/L) on antipyrine clearance. The results indicate that the inhibition of cyclooxygenase activity reduces placental transfer and that the effects of these inhibitors are reversed by carbacyclin. This study suggests that the use of cyclooxygenase inhibitors during pregnancy could compromise the developing fetus by reducing placental transfer. PMID- 3111264 TI - Technical aspects of intravascular intrauterine transfusions: lessons learned from thirty-three procedures. AB - Our technique for performing intravascular transfusions is described and four failed attempts are presented. The appropriate choice of needle, insertion site, and premedication are discussed. A rationale for intravenous fetal muscle blockade in selected cases is presented and a transfusion setup designed to minimize movement of the needle hub is described. Finally, the judicious use of intraperitoneal transfusions in some cases is suggested. PMID- 3111265 TI - Effect of refrigeration on microbial growth in the Blairex Water Purifier. AB - The Blairex Water Purifier is designed to make tap water into purified water that can be used to make saline solution for soft contact lens disinfection and rinsing. The micropore filters of eight Purifiers were perforated to allow a controlled contamination by either Pseudomonas aeruginosa or Serratia marcescens. The bacterial growth was evaluated in these altered Blairex Water Purifiers under refrigerated and unrefrigerated conditions. Those Purifiers that were refrigerated showed significantly less bacterial growth than those Purifiers that were kept at room temperature between samplings. Our findings imply that soft contact lens wearers may reduce the level of microbial growth in undamaged Purifiers by refrigerating the Purifiers between uses. PMID- 3111268 TI - Human remains of Homo sapiens neanderthalensis from the pleistocene deposit of Santa [corrected] Croce Cave, Bisceglie (Apulia), Italy. AB - The paper deals with a Neanderthal human femur, recovered during excavations in Santa [corrected] Croce Cave, Bisceglie. The cave also yielded Mousterian lithic industry and fauna indicating a paleoclimate condition with dry-warm tendency and savannah landscape. Metrical, morphometrical, and morphological analysis, and the comparison with Neanderthal specimens show that the femur belonged to an adult individual. It particularly shows great affinities with the analogous specimens from La Ferrassie 1 and 2, Spy 2, and Fond de Foret, which are similar in size and, above all, show similar archaic morphological traits. PMID- 3111266 TI - Immunophenotypic criteria for the diagnosis of non-Hodgkin's lymphoma. AB - This study examines the immunohistologic profiles of a large series of histologically proven benign and malignant lymphoproliferative processes in order to define immunophenotypic criteria useful in the diagnosis of non-Hodgkin's lymphoma. Using a method of analysis relying solely on immunoarchitectural features of a given case, the authors were able to define immunologic criteria capable of differentiating benign from malignant lymphoid processes independent from conventional morphologic analysis. In general, these criteria involved identification of abnormal expression or loss of antigens in B- and T-lineage populations. Among B-lineage populations the following features were associated with malignant histology: 1) light-chain-restricted B lineage, 2) light chain -B lineage, 3) Leu-1+ B lineage, 4) L60+ B lineage, 5) 41H+, Ki-67+ B lineage, 6) loss of pan-B antigens, and 7) LFA-1-B lineage. Among T-cell populations outside the thymus, phenotypes associated with malignancy included 1) loss of pan-T antigens (including loss of the beta chain of the T-cell antigen receptor), 2) coexpression or loss of T-subset antigens, 3) Leu-6+ T-lineage, and 4) MB-1+ T lineage. Application of these criteria to a series of nearly 500 cases of lymphoma indicated that over 90% of B-lineage and about 80% of T-lineage neoplasms manifested immunophenotypic abnormalities that could distinguish them from benign, reactive lymphoid processes. It is concluded that immunophenotypic analysis of lymphoproliferative lesions is sufficiently sensitive and specific to confirm the histologic diagnosis of lymphoma in the vast majority of cases seen in clinical practice. Furthermore, in difficult cases or those with limited material or poor histology, immunophenotypic analysis may be the only means of making a definitive diagnosis. PMID- 3111267 TI - A role for thromboxane in complement-mediated glomerular injury. AB - The membrane attack complex (MAC) of complement (C) has been shown to stimulate prostaglandin (PG) and thromboxane (Tx) synthesis in nucleated cells. Because glomerular epithelial cell injury and altered permeability in rat membranous nephropathy are mediated by the MAC, the authors examined whether MAC-induced proteinuria is linked to glomerular prostanoid synthesis. In kidneys containing non-nephritogenic, non-C-fixing gamma 2 sheep anti-Fx1A (planted antigen) that were perfused in vitro with C-fixing guinea pig anti-sheep IgG and a C source (fresh human plasma, 50% vol/vol in buffered bovine albumin), heavy proteinuria developed, reaching 4.27 +/- 1.20 mg/min/g at 100-120 minutes (n = 8). Cyclooxygenase blockade with 10(-4) M indomethacin (n = 6) inhibited urinary PGE2 excretion (569 +/- 47 to 124 +/- 18 pg/min/g, P less than 0.001) and lowered proteinuria (1.06 +/- 0.42 mg/min/g, P less than 0.001). Reduced protein excretion (0.88 +/- 0.12 mg/min/g, n = 6, P less than 0.001) also occurred with inhibition of Tx synthetase by OKY-046, 10(-4) M, a dose that was shown in separate perfusions to inhibit urinary TxB2 excretion by greater than 85%. Control kidneys, without planted antigen and perfused with anti-sheep IgG and plasma, excreted 0.30 +/- 0.05 mg protein/min/g (n = 6). Because inulin clearance was reduced by indomethacin, renal hemodynamic factors may have contributed to the reduction in proteinuria observed with this drug. However, insulin clearance was not significantly affected by OKY-046, implying that inhibition of Tx synthetase reduced proteinuria independently of changes in renal hemodynamics. Thus, proteinuria in rat membranous nephropathy is due to MAC-dependent glomerular epithelial injury and is mediated, in part, by Tx. PMID- 3111269 TI - Upper pleistocene fossil hominids from Sri Lanka. AB - Between 1978 and 1983 hominid skeletal remains were collected from the cave sites of Batadomba lena and Beli lena Kitulgala in Sri Lanka (formerly Ceylon). These are the most ancient specimens of anatomically modern Homo sapiens found thus far in South Asia, radiocarbon dates placing them in the Upper Pleistocene. Morphometric analysis of the remains of some 38 individuals from the two sites indicates that these populations were characterized by medium stature, moderate to pronounced cranial and postcranial robusticity, medium-size permanent tooth crown measurements, prognathic alveolar facial proportions, and low incidence of osseous and dental pathological conditions. Comparisons of these ancient Sri Lankans with other prehistoric skeletal series from South Asia and elsewhere support the hypothesis that muscular-skeletal robusticity was a significant physical adaptation of earlier hunting-foraging populations. A trend towards reduction of sexual dimorphism and development of more gracile body form and smaller teeth appears to have accelerated with the socioeconomic transition to food-production strategies involving agriculture and pastoralism and refinement of technologies for food procurement and preparation, as documented by morphometric studies of later prehistoric inhabitants of South Asia. PMID- 3111270 TI - Hominid footprints at Laetoli: facts and interpretations. AB - The history of discovery and interpretation of primate footprints at the site of Laetoli in northern Tanzania is reviewed. An analysis of the geological context of these tracks is provided. The hominid tracks in Tuff 7 at Site G in the Garusi River Valley demonstrate bipedality at a mid-Pliocene datum. Comparison of these tracks and the Hadar hominid foot fossils by Tuttle has led him to conclude that Australopithecus afarensis did not make the Tanzanian prints and that a more derived form of hominid is therefore indicated at Laetoli. An alternative interpretation has been offered by Stern and Susman who posit a conforming "transitional morphology" in both the Tanzanian prints and the Ethiopian bones. The present examines both hypotheses and shows that neither is likely to be entirely correct. To illustrate this point, a reconstruction of the foot skeleton of a female A. afarensis is undertaken, and the results are compared to the Laetoli tracks. We conclude that A. afarensis represents the best candidate for the maker of the Laetoli hominid trails. PMID- 3111271 TI - Angiotensin II stimulates phospholipases C and A2 in cultured rat mesangial cells. AB - Angiotensin II stimulates prostaglandin (PG) E2 formation in mesangial cells cultured from rat renal glomeruli. The interactions between angiotensin II and PGE2 are important in modulating glomerular function. We examined the mechanism for stimulation of PGE2 production in mesangial cells using the putative diacylglycerol-lipase inhibitor RHC 80267 and trifluoperazine (TFP), an agent interfering with Ca2+-CaM-mediated processes. Although RHC 80267 inhibited diacylglycerol-lipase activity in mesangial cells, it did not influence PGE2 production in response to either angiotensin II or A23187. In contrast, TFP (50 microM) inhibited basal PGE2 production and stimulation by angiotensin II and A23187. TFP also decreased 14C release in response to angiotensin from cells prelabeled with [14C]arachidonic acid, which was associated with inhibition of 14C loss from phosphatidylinositol. In cells prelabeled with 32P, orthophosphate angiotensin II caused a rapid hydrolysis of phosphatidylinositol 4,5-bisphospate. TFP enhanced 32P labeling of phosphatidylinositides, but did not prevent the loss of phosphatidylinositol 4,5-bisphosphate in response to angiotensin. This was verified in cells prelabeled with myo-[3H]inositol where angiotensin stimulated formation of [3H]inositol trisphosphate. TFP enhanced formation of [3H]inositol trisphosphate both under basal- and angiotensin II-stimulated conditions. Thus TFP did not inhibit phospholipase C activation by angiotensin. Angiotensin II caused marked increases in [32P]lysophospholipids, indicating activation of also phospholipase A2. This process was inhibited by TFP. Taken together, these results are consistent with stimulation of both phospholipase C and A2 by angiotensin, the latter step responsible for the release of arachidonic acid and PGE2 formation. The activation of phospholipase A2, but not that of phospholipase C, is inhibited by TFP, perhaps by interference with calmodulin-dependent steps. PMID- 3111272 TI - A potential mechanism of DL-beta-hydroxybutyrate-induced malformations in mouse embryos. AB - DL-beta-Hydroxybutyrate (DL-BOHB) is teratogenic to rodent embryos in culture, but the biochemical mechanism(s) responsible for the induction of malformations has not been elucidated. Thus, to delineate a potential mechanism, the interaction of the ketone body with embryonic glucose metabolism was investigated. Mouse embryos were exposed in whole embryo culture to DL-BOHB or each isomer separately during the period of neurulation. The results demonstrate that DL-BOHB inhibits glucose oxidation by the pentose phosphate pathway (PPP) with no concomitant effect on Krebs cycle or glycolysis. Furthermore, decreased rates of embryonic uridine monophosphate and DNA synthesis were produced by DL BOHB, whereas orotate synthesis was unaffected, thereby suggesting that the availability of ribose moieties synthesized by the PPP was compromised. This hypothesis was supported by the observation that addition of ribose to DL-BOHB containing medium reduced the incidence of ketone body-induced neural tube defects and maintained the rates of DNA synthesis at control levels. Furthermore, these biochemical alterations are due to the synergistic effects of the D and L isomers and may be related to changes in redox states. PMID- 3111273 TI - Relationship between ornithine decarboxylase activity and gastric damage. AB - Hypertonic NaCl increases the activity of gastric mucosal ornithine decarboxylase (ODC). Intragastric administration of concentrated NaCl solution also induces ulcers in the glandular gastric mucosa. The relationship between ODC activity and gastric mucosal damage and the significance of ODC increases in hypertonic NaCl treated rats are unknown. Rats were fasted 24 h before being given 1.0 ml of 3.4 M NaCl, 120 mM aspirin in 100 mM HCl or 50% ethanol intragastrically. The oxyntic gland mucosa was removed and assayed for ODC and in some experiments DNA, RNA, and protein content. DNA, RNA, and protein content were decreased by 3.4 M NaCl, and these decreases were much greater if ODC was inhibited by pretreatment with alpha-difluoromethylornithine (DFMO). Both aspirin and 3.4 M NaCl induced ODC activity 6 h later. However, DFMO increased the lesion index only in NaCl-treated rats. Although ethanol produced damage, it had no effect on ODC levels, and DFMO did not alter the severity of ethanol lesions. When different concentrations (0.4, 0.8, 1.6, 2.5, and 3.4 M) of NaCl were administered, ODC activities were increased 6 h later in rats receiving 1.6, 2.5, and 3.4 M NaCl but not lower concentrations. Gross lesions appeared in response to the 2.5 M dose and increased with increasing NaCl concentration. However, microscopic damage of the gastric mucosa occurred at all the concentrations tested. These data show that 1) ODC activation is not necessarily produced by damage, 2) in the case of NaCl, increasing damage increases ODC, and 3) ODC appears to have a role in the prevention of a recovery to damage caused by NaCl. PMID- 3111275 TI - Renal effects of cyclooxygenase inhibition in the pregnant rat. AB - Experiments were performed to investigate the effects of acute cyclooxygenase inhibition on renal hemodynamics in mid and late pregnant rats. In micropuncture studies in the control state, midterm pregnant rats exhibited increased single nephron glomerular rate (SNGFR) and no change in glomerular or arterial blood pressures. In late pregnancy, SNGFR was no longer significantly elevated, glomerular pressure was similar, and arterial pressure was depressed compared with the virgin. Cyclooxygenase inhibition led to significant increases in single nephron and whole-kidney filtration and flow in mid and late pregnant rats. This effect was also seen in the virgin control group, and all groups involved a selective renal vasodilation without change in blood pressure. In the absence of anesthesia and surgical stress, cyclooxygenase inhibition had little effect in virgin or pregnant chronically catheterized rats. These studies indicate that the cyclooxygenase-dependent arachidonic acid metabolites are not the agents directly responsible for the gestational rise in the glomerular filtration rate. PMID- 3111274 TI - Oxygen metabolite-induced cytotoxicity to cultured rat gastric mucosal cells. AB - Reactive oxygen metabolites have been reported to be responsible for the pathogenesis of ischemia-induced gastric mucosal lesions. We have investigated the possible protective effect of specific enzymes and oxygen radical scavenging agents on oxygen metabolite-induced injury to cultured gastric mucosal cells. Oxygen-reactive metabolites were generated by 1 mM xanthine and 10-100 mU/ml xanthine oxidase. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells. Xanthine oxidase caused a dose-dependent increase of 51Cr release in the presence of 1 mM xanthine. Catalase (an enzyme that reduces hydrogen peroxide) diminished xanthine-xanthine oxidase-induced 51Cr release in a dose-dependent manner. Superoxide dismutase (a scavenger of superoxide radical) failed to affect the amounts of 51Cr release induced by xanthine plus xanthine oxidase. Pretreatment with diethyl maleate, which depletes intracellular glutathione, potentiated oxygen radical-mediated 51Cr release dose dependently. The presence of ferrous ion or ethylenediaminetetraacetic acid-chelated iron, which promote the formation of hydroxyl radical, did not alter xanthine-xanthine oxidase-induced cellular injury. Furthermore, agents that inactivate hydroxyl radical also failed to protect the cells from oxygen metabolite-induced injury. We conclude that in vitro oxygen metabolites, extracellularly generated, have a direct toxic effect on gastric mucosal cells; hydrogen peroxide is a major mediator of oxygen metabolite-induced gastric cell injury; the oxygen-derived superoxide and hydroxyl radicals are less toxic to gastric mucosal cells than hydrogen peroxide; and intracellular glutathione, which detoxifies hydrogen peroxide, may be involved in antioxidant defense mechanisms. PMID- 3111276 TI - Facilitated transfer of glucose from blood into perilymph in the rat cochlea. AB - The transport of glucose into cochlear endolymph, perilymph of scala vestibuli and perilymph of scala tympani, and cerebrospinal fluid (CSF) was studied after intravenous administration of tracers of D-glucose, L-glucose, and 3-O-methyl-D glucose in anesthetized rats. The data showed that D-glucose concentrations in perilymph of scala vestibuli, perilymph of scala tympani, and CSF were approximately 50%, and in endolymph less than 10%, that in plasma; D-glucose concentration in perilymph of scala vestibuli, perilymph of scala tympani, and CSF increased as a linear function of that in plasma; D-glucose entry into perilymph of scala vestibuli, perilymph of scala tympani, and CSF was more rapid than that of L-glucose; after infusion of 3-O-methyl-D-glucose, but not after that of mannitol, both the D-glucose concentration ratio of perilymph over plasma and D-glucose transfer into perilymph were lowered. These results indicate that D glucose enters into perilymph of scala vestibuli by a facilitated transport, possibly located at the blood-perilymph barrier. PMID- 3111277 TI - Impact of psychiatric comorbidity on length of hospital stay for medical/surgical patients: a preliminary report. AB - The impact of psychiatric comorbidity on the length of hospital stay was addressed in a study of all medical/surgical patients discharged in 1984 from the Mount Sinai Hospital in New York City (N = 37,370) and Northwestern Memorial Hospital in Chicago (N = 21,889). At both hospitals the mean +/- SD length of stay of the patients with psychiatric comorbidity was significantly longer than that of the other patients: 19.8 +/- 33.3 versus 9.2 +/- 15.3 days at Mount Sinai Hospital and 13.7 +/- 27.7 versus 8.3 +/- 13.2 days at Northwestern Memorial Hospital. Early identification of patients with psychiatric comorbidity would permit appropriate psychosocial intervention, which might shorten their hospital stays. PMID- 3111278 TI - Growth hormone response to edrophonium in Alzheimer's disease. AB - Neuropathologic data from patients with Alzheimer's disease indicate the presence of neurofibrillary tangles in hypothalamic regions associated with regulation of pituitary hormone release. The authors explored the hypothesis that cholinergic projections to hypothalamic nuclei controlling pituitary growth hormone (GH) release degenerate in Alzheimer's disease. Integrity of cholinergic regulation was tested by assaying the GH response to a presynaptic cholinergic challenge. After administration of the choline esterase inhibitor edrophonium, the peak GH response was 14 ng/ml in healthy elderly control subjects and only 2 ng/ml in Alzheimer's patients. The magnitude of GH blunting was correlated with cognitive and functional deficits. Possible implications of these data for enhanced accuracy in the diagnosis of dementia are discussed. PMID- 3111279 TI - Treatment of severe obsessive-compulsive disorder with fluvoxamine. AB - Ten obsessive-compulsive patients received single-blind treatment with fluvoxamine, a selective serotonin reuptake inhibitor, for several weeks following at least 2 weeks of placebo. The group showed significant improvement, as measured by several clinical scales and self-ratings; six patients were judged responders. Fluvoxamine appears effective in treating severe obsessive-compulsive disorder. PMID- 3111281 TI - Field trial of vaccination against American trypanosomiasis (Chagas' disease) in domestic guinea pigs. AB - Domestically bred South American guinea pigs received 3 to 5 immunizing intradermal inocula of 28 X 10(6) live attenuated Trypanosoma cruzi epimastigotes (TCC strain) per kg. These inocula were unable to produce patent infections or to propagate through vectors. Groups of experimental and control guinea pigs were exposed to natural T. cruzi infection in a field yard for periods of up to 551 days. Xenodiagnoses were applied periodically to all animals. This showed that the incidence of natural T. cruzi infection was significantly lowered at various periods post-exposure. The final proportion of infected animals was 39% (20/51) among vaccinees vs. 63% (32/51) among controls (P less than 0.02). The protective effect was exerted particularly upon males and lasted for over a year in one experimental series (infection in 1/7 vaccinees vs. 6/7 controls, P = 0.014). Vaccination reduced vector transmission rates from 38% to 18% (P less than 0.001). These results agree with previous laboratory experiments in showing a partial resistance which does not eliminate residual T. cruzi infection. However, the field work indicates that even this kind of resistance may have epidemiological impact, reducing both the number of reservoirs spreading the disease and the rate of vector transmission. PMID- 3111280 TI - CO2 challenge of patients with panic disorder. AB - In an open trial, five of eight panic disorder patients and none of five control subjects panicked after inhalation of two breaths of 35% CO2 and 65% O2; none panicked after placebo. Using 35% CO2 to induce panic is safe, simple, and well tolerated and may provide a valuable laboratory model of panic. PMID- 3111282 TI - Lack of demonstrable density-dependent fecundity of schistosomiasis mansoni: analyses of Egyptian quantitative human autopsies. AB - Conflicting interpretations regarding the fecundity of schistosomes infecting human beings have arisen and are, in part, due to the inability to directly measure the parameters. The inability to experimentally manipulate human beings necessitates the use of surrogate variables, i.e., number of eggs per gram of feces, as an indicator of worm burden. This study reanalyzes data from quantitative autopsies performed in Egypt by Cheever and colleagues on individuals with active Schistosoma mansoni infections. Exploratory regression analysis of the relationship of female worms recovered to eggs/g of feces and of female worms to eggs retained in host tissues suggests a linear relationship in both cases. Over the observed range of female worms recovered from an individual human being, the estimated worm fecundity, as measured by the number of eggs either in feces or retained in tissues per female worm, is not significantly different from a constant value. Hence, density-dependent fecundity of S. mansoni in the human host, as suggested by others, is not demonstrated in these data. PMID- 3111283 TI - Variation of hepatic fibrosis and granuloma size among mouse strains infected with Schistosoma mansoni. AB - To investigate the relation between the size of circumoval granulomas and hepatic fibrosis, a variety of mouse strains infected with Schistosoma mansoni were examined and the number of eggs in the tissues, the fibrotic responses to the eggs, and the volume of the granulomas were determined. Marked differences in granuloma volume and in hepatic fibrosis were found between mouse strains, and those strains with the largest granulomas also showed the most hepatic fibrosis. On the other hand no significant correlation between granuloma size and hepatic fibrosis was found in the progeny of the F2 generation and backcrosses between F1 mice and the parental strains when crosses were made between Nmri mice (high granuloma volume and high fibrosis) and C57BL/6 mice (low granuloma volume and low fibrosis). Hepatic fibrosis per egg decreased with increasing infection intensity while granuloma volume was unaffected, indicating that fibrosis and granuloma size are at least in part modulated by different factors. The number of eggs found in the tissues per worm pair and the proportion of eggs in the liver also decreased as infection intensity increased. Some influence of the major histocompatibility complex on both granuloma size and fibrosis was found. Congenic mice on the C57BL/10 and C3H/HeSn backgrounds showed larger granulomas in H-2b than in H-2k mice, but no such correlation was found in comparing C57BL/6 mice with B6.H-2k mice. Less hepatic fibrosis was found in B10.M (H-2f), B10.SM (H-2v), and B10.RIII (H-2r) animals than in C57BL/10 mice. The regulation of granuloma size and of hepatic fibrosis is clearly complex and involves genes both outside of and within the major histocompatibility complex. PMID- 3111285 TI - Automatic extraction of intensity-intervention scores from a computerized surgical intensive care unit flowsheet. AB - Systems that objectively score severity of illness and intensity of patient care interventions have been used to guide the appropriate use of intensive care facilities, provide information on nurse staffing ratios, validate subjective classifications of patient illness, and normalize scientific and financial studies for severity of illness. Existing scoring systems require a well-trained observer to perform a thorough chart review to complete manual scoring forms. We have designed a new system in which computerized intensity-intervention scores are automatically extracted from electronic intensive care unit flowsheets, eliminating both manual labor and potential observer variation. In prospective studies, these computerized scores correlated well with manual TISS scores, intensive care unit mortality, intensive care unit length of stay, hospital length of stay, and a subjective classification of patients to graded levels of hospital care. Such automated scores may be used for real-time allocation of health care resources and normalization of prospective studies for severity of illness. PMID- 3111284 TI - Vaccine-induced immunity in mice against Schistosoma mansoni trickle cercarial infections. AB - Experiments were performed to determine the level of protection in immunized mice to multiple small (trickle) Schistosoma mansoni cercarial challenges. C57BL/6 mice were immunized with either 50 Krad-irradiated cercariae or a soluble worm antigenic extract injected intradermally in conjunction with the adjuvant BCG. A series of cercarial challenges (40 cercariae per exposure), beginning approximately one month after immunization, was given at 4-week intervals. To prevent any contribution of egg-related pathology, the mice were exposed to male cercariae only. The results showed that highly significant levels of protection developed at all times after cercarial challenge. Regardless of the type of immunization or the number of cercarial challenges, the levels of protection which appeared after one, two, three, or four challenge exposures were nearly identical, and equalled those in mice exposed at a single time to a cumulative total of the several exposures. As expected, titers of anti-schistosome antibodies were higher in the immunized and challenged groups than in those challenged alone, and titers increased anamnestically after challenge infection. However, increased antibody titers were not associated with increased resistance in trickle challenged mice. Overall, we showed that the level of vaccine-induced immunity does not change, under these conditions, in the face of repeated cercarial challenges. Also, these results show that single mass cercarial challenges may legitimately be used in experimental situations to assess the effectiveness of vaccines which might be used in subjects repeatedly exposed to cercariae in field situations. PMID- 3111286 TI - Injuries of the duodenum. AB - The records of 115 patients with a duodenal injury have been reviewed. The majority of the patients (83 percent) were treated with primary repair of the injury. Twelve patients underwent duodenal diverticulization. The mortality rate in all 115 patients was 12 percent, in 105 patients who survived more than 48 hours 4 percent, and in 26 patients with pancreaticoduodenal injury 15 percent. Vascular injury was the major cause of early death. Enteric perforations were present in 75 percent of the patients with sepsis. The majority of patients with associated pancreatic injury had primary repair and did not have pancreaticoduodenal complications. Duodenal fistula continues to be a serious postoperative complication. Primary repair with drainage is the preferred treatment. Gastrostomy and feeding jejunostomy are useful adjuncts. A more complex operation should be reserved for a highly select group of patients with severe duodenal injury. PMID- 3111287 TI - Clinical experiences of petit mal. AB - Petit mal is a condition characterized by absences accompanied on EEG by discharges of 3/sec spike and waves lasting more than 3-4 seconds. In 145 patients with pure petit mal (PPM) these were the only findings. They were associated with other types of seizures (APM) in 52 subjects and with myoclonic jerks of the upper limbs. (MPM) in 8. Clinical and EEG normalization was obtained in 93/111 patients with PPM with adequate therapy (84%), while the same outcome was observed in 7/31 (22%) of the subjects without adequate therapy. In the group with APM, clinical and EEG normalization was obtained in 26/34 (76%), while it was observed in 3/18 (16%) of the patients who received inadequate therapy. Among the patients with MPM, clinical but not EEG normalization was obtained in 4/8. The personal history showed a high percentage of febrile convulsions. IPS was also frequently positive. The prognosis of PM seems to be mainly related to adequate therapy. The presence of other types of seizures does not significantly modify the prognosis provided that the therapy is adequate. It is, however, important to note that signs or symptoms of neurologic impairment were rare in this group of patients, probably due to the criteria chosen for the selection of patients. PMID- 3111288 TI - Muscle involvement in pyruvate dehydrogenase complex (PDHC) deficiency. AB - Muscle biopsies from a 13-month-old female infant with a delay in developmental milestones, lactic acidosis and visual disturbance, and a 6 year-old female with frequent epileptic fits are described. Biochemical studies of biopsied muscles and skin fibroblasts demonstrated markedly decreased pyruvate dehydrogenase complex (PDHC) activity to about 16% of normal value. Muscle histochemistry in both patients showed disorganized intermyofibrillar networks containing large diformazan granules on NADH-TR, small angulated fibers with high nonspecific esterase (NSE) activity and basophilic fibers. Ragged-red fibers and increased lipid droplet accumulation were absent. Patient 1 had increased numbers of type 2C fibers (11.3%) and mild fiber type grouping. On electron microscopy, most mitochondria were nearly normal. There were focal aggregates of mildly enlarged mitochondria in the subsarcolemmal areas in both patients. Morphometric study showed that the mean mitochondrial size and the mitochondrial percentage of fiber volume were not significantly different amongst patients and normal controls. PMID- 3111289 TI - [Sodium cromoglycate in allergic eye diseases]. PMID- 3111290 TI - [Use of sodium cromoglycate aerosol in patients with asthma and chronic bronchitis]. PMID- 3111291 TI - [Topical sodium cromoglycate in allergic rhinitis]. PMID- 3111292 TI - The effect of Ro15-1788 (Anexate) on conscious sedation produced with midazolam. AB - A double-blind cross-over randomised study was performed to investigate whether Ro15-1788 (Anexate) adequately reversed the conscious sedation with midazolam so that patients were clinically recovered and fit for discharge quicker than when midazolam was used alone. Twenty-eight healthy patients between 18 and 34 years sedated with midazolam for bilateral 3rd molar surgery, one side being operated on at each visit. Ro15-1788 or normal saline (placebo) was given at the end of the surgical procedure at the first visit and the alternative at the second visit. Recovery with Ro15-1788 was significantly quicker than with the placebo, both by subjective (86%) and objective (93%) evaluation. Patients' evaluation indicated that only 61% were more alert at home with Ro15-1788. Postoperative adverse effects were similar in both groups. PMID- 3111293 TI - An evaluation of five carbon dioxide analysers for use in the operating theatre and intensive care unit. AB - Five commercially available carbon dioxide analysers were assessed with respect to accuracy, response time, stability, the effect of water vapour and the effect of rebreathing. Two side-stream sampling analysers (Datex Normocap and Engstrom Eliza) and one main-stream sampling analyser (Hewlett-Packard Capnoshot) were found to be satisfactory for use both in the operating theatre and intensive care unit. The Instrumentation Laboratory (IL) 200, a side-stream monitor, performed satisfactorily but neither it nor the Siemens Sirecust 404, a main-stream monitor, has the facility to compensate for the presence of nitrous oxide. The Siemens analyser, in the form tested, could not be recommended for clinical use, as it was less accurate than the other monitors, could not detect rebreathing, and was subject to fluctuations when used with gas mixtures saturated with water vapour. PMID- 3111294 TI - Measurement of epsilon-N-trimethyllysine in human blood plasma and urine. AB - A method for measurement of epsilon-N-trimethyllysine in human blood plasma and urine is described. An internal standard, delta-N-trimethylornithine, was added to plasma and urine specimens and the mixtures were deproteinized and/or hydrolyzed. Preliminary purification of epsilon-N-trimethyllysine and delta-N trimethylornithine was achieved by sequential cation-exchange--anion-exchange chromatography. Amino acids in the column eluates were derivatized with o phthalaldehyde and mercaptoethanol, and were separated by isocratic reversed phase high-performance liquid chromatography in the presence of an ion-pairing reagent. Quantitation was achieved by post-column fluorometry. The limit of detection was 5 pmol of epsilon-N-trimethyllysine injected into the chromatograph. The procedure was suitable for determination of epsilon-N trimethyllysine in 1 ml of plasma or 0.2-0.4 ml of urine. The method was applied to measurements of epsilon-N-trimethyllysine in plasma and urine of four systemic carnitine deficiency patients and six normal subjects. Plasma epsilon-N trimethyllysine concentration was significantly lower in systemic carnitine deficiency patients compared to normal individuals, but no significant difference in urinary epsilon-N-trimethyllysine excretion was observed between the two groups. PMID- 3111295 TI - Tresyl activation of a hydroxyalkyl ligand for coupling to a hydrazide gel: stable immobilization of T-2 toxin for affinity purification of T-2 antibody. AB - A stable T-2 hydrazide gel is prepared by activating T-2 toxin with tresyl chloride followed by coupling to agarose-adipic acid hydrazide. Utilized as an affinity chromatography column, this T-2 hydrazide gel purifies a monoclonal antibody for T-2 in high yield directly from ascites fluid. Specific antibody trapped on the column is eluted either with excess T-2 or at pH 11.6. Much less successful are two other T-2 affinity columns that were prepared and evaluated: T 2 bovine serum albumin Affi-Gel 15 and T-2 hexylamine Sepharose. PMID- 3111296 TI - Purification of NADPH:cytochrome c (cytochrome P-450) reductase from hamster liver microsomes by detergent extraction and affinity chromatography. AB - NADPH:cytochrome c (cytochrome P-450) reductase (Fp) from hamster liver microsomes has been purified to near homogeneity using a simple and rapid method. Microsomes were treated with the detergent Chaps (3-[(3 cholamidopropyl)dimethylammonio]propanesulfonic acid) in combination with 0.07% protamine sulfate and then centrifuged to pellet insoluble material. While over 60% of the total microsomal protein was solubilized, all Fp activity remained in the pellet. Fp was extracted from the Chaps-insoluble material using a combination of the detergents sodium cholate and Lubrol PX. This treatment resulted in a fivefold increase in Fp specific activity and allowed direct processing of the enriched Fp fraction by 2',5'-ADP agarose affinity chromatography. The purified Fp had a total flavin content of 23 nmol/mg protein (flavin adenine dinucleotide:flavin mononucleotide ratio = 1:1), a specific activity of 26,000 units/mg protein at 22 degrees C using cytochrome c as electron acceptor, and migrated as a single band on sodium-dodecyl sulfate polyacrylamide gel electrophoresis with a relative molecular weight of 76,000. The purity, specific activity, and yield were nearly identical to results obtained when the flavoprotein was purified by conventional methods. This procedure eliminates the need for anion-exchange chromatography and allows for the rapid purification of large amounts of Fp suitable for use in studies concerning cytochrome P-450-mediated drug metabolism. Importantly, this method is equally effective when used to purify Fp from rat liver microsomes. PMID- 3111297 TI - Determination of biocytin. AB - Biocytin (epsilon-N-[d-biotinyl]-L-lysine) is generally undetected in serum and other body fluids of normal healthy individuals in view of the ubiquitous distribution of biotinidase. It has been suggested that biocytin may be present in serum and urine of patients with inherited biotinidase deficiency. We have developed a noncompetitive assay for biocytin based on its interaction with avidin. Biocytin can be determined in biological samples containing both biotin and biocytin. Biotin from such samples is removed by an anion-exchange resin and the biocytin is determined by the avidin-binding assay. The effect of above normal levels of biotin in the sample on the assay of biocytin is discussed. PMID- 3111298 TI - Determination of substrate specificity of carboxylases by nuclear magnetic resonance. AB - Determination of whether CO2 or HCO3- is the substrate for an enzymatic carboxylation has generally been accomplished by taking advantage of the fact that equilibration of these two compounds requires more than a minute at temperatures below 15 degrees C; thus different kinetics of carboxylation are obtained depending on whether CO2 or HCO3- is used to initiate the reaction. We report a new method using 13C18O2 as substrate for determining the CO2/HCO3- specificity of carboxylases. If CO2 is the substrate, then the 18O content of the 13C-containing product is the same as that of the 13CO2 used, whereas if HCO3- is the substrate, the 18O content is 2/3 that of the starting material. The method is independent of the detailed kinetics of the CO2/HCO3- interconversion and independent of the presence of contaminating unlabeled CO2 or HCO3-. Isotopic analysis is accomplished by 13C NMR. The method has been used to confirm that HCO3- is the substrate for phosphoenolpyruvate carboxylase. Studies of oxygen-18 isotope shifts in phosphorus NMR spectra have permitted confirmation of the observation that label is transferred from HC18O3- into Pi during the carboxylation of phosphoenolpyruvate. PMID- 3111299 TI - Analysis of reducing sugars as their chromophoric hydrazones by high-performance liquid chromatography. AB - A chromophoric hydrazide, 4'-N,N-dimethylamino-4-azobenzene sulfonyl hydrazide (DABS-hydrazide), was prepared from 4'-N,N-dimethylamino-4-azobenzene sulfonyl chloride by reaction with hydrazine. Reducing sugars were derivatized with DABS hydrazide at 50 degrees C for 120 min. The chromophoric hydrazones were separated by reversed-phase HPLC isocratically using a short column (4.6 X 50 mm) and 0.08 M acetic acid-acetone as an eluant with no sample pretreatment and were quantitated at the picomole level. This method was applied to the sugar analysis of 5 micrograms of glycoproteins. Dansyl hydrazide derivatives of sugars were also separated by this HPLC system. PMID- 3111300 TI - Synthesis of dabsylhydrazine and its use in the chromatographic determination of monosaccharides by thin-layer and high-performance liquid chromatography. PMID- 3111301 TI - The basement membrane of the persisting maternal blood vessels in the placenta of Callithrix jacchus. AB - Formation and morphology of the thickened basement membrane-like layer around the persisting maternal vessels of the Callithrix jacchus placenta were investigated from day 45 until term (day 142) using light, electron and immunofluorescence microscopy. Thickening occurs with the establishment of contacts between the vessels and the syncytiotrophoblast (day 48). Final thickness is reached at about day 100. The course of the vessels shows wide gaps where the maternal blood flows freely into the intertrabecular spaces. As revealed by electron microscopy, the extracellular sheath around the maternal vessels consists of an inner subendothelial basement membrane (3-6 microns) and an outer fibril-containing layer (2-4 microns). Cell debris is seen between the two layers and in the basement membrane. Plaques of granular and fine-filamentous material are incorporated into the fibril-containing layer. The synthesis of the basement membrane material is localized in the endothelial cells. Immunofluorescence microscopy reveals collagen types IV and V, laminin and heparan sulfate proteoglycan (BM-1) in the sheath around the persisting vessels. Fibronectin occurs only in certain areas or in the form of dots. Collagen types I and III are not seen in the region of the vascular wall. It can, therefore, be assumed that the subendothelial layer represents a genuine basement membrane; the fibrils consist of collagen type V and the plaques contain fibronectin. The existence of the thick perivascular sheath is attributed to the persistence and stability of the maternal vessels. PMID- 3111302 TI - Grand mal seizures after 2-chloroprocaine epidural anesthesia in a patient with plasma cholinesterase deficiency. PMID- 3111303 TI - Increases in arterial to end-tidal CO2 tension differences after cardiopulmonary bypass. PMID- 3111304 TI - Ventilatory response to carbon dioxide after intramuscular and epidural fentanyl. AB - The authors compared the effects of administration of fentanyl 200 micrograms on the ventilatory response to carbon dioxide in two groups of nine healthy unpremedicated subjects: one group received fentanyl as an intramuscular injection; in the other group, fentanyl was injected into the epidural space. In the intramuscular group, the slope of the ventilatory response to CO2 did not decrease significantly. In the epidural group, the slope of the ventilatory response to CO2 decreased significantly from 2.48 +/- 1.05 to 1.77 +/- 0.7, 1.74 +/- 0.7, and 2.07 +/- 0.74 L X min-1 X mm Hg-1 at 30, 60, and 120 min after injection (chi +/- SD, P less than or equal to 0.05), respectively. At each time of the study, plasma fentanyl levels were significantly lower in the epidural group than in the intramuscular group (P less than or equal to 0.05). These results suggest that epidural fentanyl induces a nonsystemic ventilatory depression that may be due to the rostral spread of the drug. PMID- 3111305 TI - Effect of meperidine on oxygen consumption, carbon dioxide production, and respiratory gas exchange in postanesthesia shivering. AB - Meperidine has been used to suppress postanesthesia shivering. However, its efficacy to date has only been assessed by observation of visible shivering. We measured the effect of meperidine on oxygen consumption (VO2), carbon dioxide production (VCO2) and pulmonary gas exchange in 14 otherwise healthy patients shivering after general anesthesia. Meperidine successfully suppressed visible shivering in all patients and was associated with significant decreases in VO2, and VCO2 and minute ventilation (VE) but not with return to basal levels. Arterial PCO2 levels remained unchanged at normal, whereas significant improvements occurred in pH and bicarbonate levels. Meperidine is an effective method of reducing the elevated metabolic demand of shivering. PMID- 3111306 TI - Treatment of acute respiratory failure by extracorporeal carbon dioxide elimination performed with a surface heparinized artificial lung. PMID- 3111307 TI - Prolonged hypocapnia does not alter the rate of CSF production in dogs during halothane anesthesia or sedation with nitrous oxide. AB - This study examined the effect of prolonged hypocapnia on the rate of cerebrospinal fluid (CSF) production (Vf) and on other CSF dynamics in dogs. Determination of CSF values began 2 h after the onset of hypocapnia and continued for an additional 3 h. Two separate methods were used to determine Vf: modified open ventriculocisternal perfusion and closed ventriculocisternal perfusion. Dogs were examined both during hypocapnia plus anesthesia with halothane (0.8%) and nitrous oxide (66%), and during hypocapnia plus sedation with nitrous oxide (66%) and halothane (0.15%) combined with bupivacaine (0.75%) infiltration of wound edges. There were no differences in Vf measured by the two methods. At the first measurable time period, mean Vf values during hypocapnia and halothane anesthesia, 32 +/- 9 and 35 +/- 10 microliters/min (mean +/- SD), were lower than mean Vf values during hypocapnia and nitrous oxide sedation, 48 +/- 11 and 49 +/- 8 microliters/min. Vf did not change significantly during 3 h of hypocapnia. For both halothane anesthesia and nitrous oxide sedation, mean Vf values during hypocapnia were not significantly different from Vf values previously reported during normocapnia, 31 +/- 12 and 33 +/- 12 microliters/min and 44 +/- 13 and 47 +/- 14 microliters/min, respectively. The results indicate that prolonged hypocapnia does not decrease Vf, and, therefore, reduction of Vf is probably not one of the causes for reduction of elevated CSF pressure by prolonged hypocapnia. Regarding the other data on CSF dynamics, CSF pressure at hypocapnia was similar to that at normocapnia, suggesting that hypocapnia did not affect resistance to reabsorption of CSF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111308 TI - Glucose: a reevaluation of its intraoperative use. PMID- 3111309 TI - Effect of halothane on critical levels of oxygen transport in the anesthetized newborn lamb. AB - A critical level of oxygen transport has been defined as the level which is required to maintain tissue oxygen uptake (VO2). If halothane reduces the susceptibility to hypoxia, it should lower the critical levels of both O2 delivery (DO2) and arterial oxygen tension (pO2). To test this hypothesis, 12 newborn lambs were anesthetized with either fentanyl and pancuronium (control group) or fentanyl, pancuronium, and 1.1% (1 MAC) halothane (halothane group). Baseline measurements of hemoglobin, cardiac output (CO), arterial and mixed venous pO2, and saturation were obtained on FIO2 1.0, and repeated with FIO2 .21, .15, and .10. O2 delivery (CO X CaO2) and O2 consumption were calculated from measured parameters. Critical levels were selected using a system of repetitive linear regression. Halothane decreased baseline O2 consumption (12.1 +/- 0.7 to 8.4 +/- 0.4 cc X kg-1 X min-1, x +/- SEM, P less than .001, unpaired t test), but caused similar reductions in cardiac output (235 +/- 15 to 132 +/- 15 cc X kg-1 X min-1, P less than .001) and O2 delivery (29.2 +/- 2.9 to 20.2 +/- 1.6 cc X kg-1 X min-1, P less than .05). Addition of halothane decreased the critical level of O2 delivery from 17.9 to 14.3 cc X kg-1 X min-1, but had no effect on the critical level of arterial pO2 (control group, 47 mmHg halothane, 46 mmHg). Peripheral oxygen utilization was mildly reduced during halothane anesthesia, as evidenced by a decrease in oxygen extraction (control group O2 extraction rate = 0.63; halothane group O2 extraction = 0.51, P less than .05, unpaired t test).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111310 TI - Separate lung blood flow in anesthetized dogs: a comparative study between electromagnetometry and SF6 and CO2 elimination. AB - Anesthetized, prone dogs were intubated with a double-lumen endobronchial tube, and the lungs were ventilated independently. Three methods of recording differential blood flow were compared during unilateral lung hypoxia: electromagnetic flow measurement, flow probes being fitted onto each main pulmonary artery after thoracotomy (QPr); SF6 elimination from each lung, the inert gas being continuously infused into a central vein (QSF6); and CO2 elimination (QCO2). During control conditions (100% O2 to both lungs), the test lung QPr was 54% of cardiac output, and corresponding QSF6 and QCO2 were 56% and 52%, respectively. Hypoxic challenge with 8% O2 to the test lung reduced QPR, QSF6, and QCO2 by 25%, 27%, and 7%, respectively. Ventilation of the test lung with pure nitrogen reduced its blood flow further, QPr, QSF6, and QCO2 being reduced by 39%, 42%, and 23%, respectively, from initial control. A strong correlation between test lung QPr and QSF6 was seen with a slope of 0.90 (r:0.89, P less than 0.001). Only 60% of the reduction in test lung blood flow was detected by CO2 elimination, as compared to electromagnetic flow measurement or SF6 elimination. The poor results obtained with CO2 elimination can be explained by its dependence on the ventilation-perfusion ratio and the effect of oxygen tension on the CO2 binding capacity of blood (Haldane effect). The findings emphasize the necessity of using an inert, poorly soluble gas for the measurement of separate lung blood flow. PMID- 3111311 TI - [Effect of emotional pain stress on ventilatory sensitivity to a hypercapnic stimulus]. PMID- 3111312 TI - Effects of variable alphaprodine dose levels on arterial blood gases in rhesus monkeys. AB - The administration of alphaprodine submucosally in doses of 0.5, 1.0, and 1.5 mg/kg to ketaminized rhesus monkeys resulted in Po(2) levels significantly lower than those observed for controls (ketamine only) at the 10 min level. There was a significant increase in Po(2) levels between the 10 and 20 min intervals, thereafter, Po(2) levels returned toward normal and were not statistically different from baseline. Higher alphaprodine doses (1.0 and 1.5 mg/kg) resulted in a non-significant increase in Pco(2) values. Monitoring Po(2) levels during sedation seems preferable to monitoring Pco(2) in view of the findings of this study. PMID- 3111313 TI - Analysis of cardiovascular changes and arterial blood gases in patients resistant to methohexital anesthesia. AB - Two studies were done to evaluate the patient who appears to be clinically resistant to incremental methohexital infusion for general anesthesia. A retrospective study revealed that 9% of the 513 patients developed resistance to methohexital maintenance and required a volatile inhalation anesthetic supplement. The cardiovascular and arterial blood gas analysis in a prospective study failed to disclose any gross changes that would explain the physiology associated with patients resistant to methohexital anesthesia. To maintain adequate anesthesia depth, doses of methohexital ranged from .07 to .12 mg/kg/min or 4.1 to 8.2 mg/min. PMID- 3111314 TI - Joint inheritance of bovine major histocompatibility system antigens W6 and W11. PMID- 3111315 TI - Decreased expression of high affinity interleukin 2 receptors after hyposensitization to house dust. AB - The lymphoproliferative response to allergen usually decreases after long-term hyposensitization (immunotherapy). In order to delineate the working mechanism of this kind of treatment, expression of interleukin 2 receptors (IL-2 R) on house dust and phytohemagglutinin-activated lymphocytes was compared in 15 normals, 18 newly diagnosed and 28 hyposensitized asthmatic children. Interleukin 2 receptors were analyzed by fluorescent-activated cell sorter (FACS), uptake of 125I labelled anti-human IL-2R monoclonal antibody (anti-Tac), and proliferative response to recombinant IL-2 (rIL-2). The results showed that there was no difference in the expression of IL-2R among three studied groups, if IL-2R were detected by anti-Tac. When compared to the other two groups, house dust-activated lymphoblasts from new patients proliferated vigorously in the presence of very low rIL-2 (0.02 to 1.0 nM), suggesting the presence of much higher numbers of high affinity IL-2R. Decreased high affinity IL-2R may partly explain the diminished lymphoproliferation to allergen after long-term hyposensitization. PMID- 3111316 TI - T-2 toxin-enhanced resistance against listeriosis in mice: importance of gastrointestinal lesions. AB - The role of T-2 toxin-induced gastrointestinal lesions in T-2 toxin-enhanced resistance to listeriosis in mice was evaluated. The T-2 toxin-induced lesions did not cause a starvation effect sufficient to enhance resistance to listeriosis. Administration of polymyxin E markedly reduced the gram-negative intestinal microflora and did not eliminate the toxin-induced resistance to listeriosis. The T-2 toxin did not cause an increased expression of Ia surface antigens on peritoneal macrophages. Thus, toxin-induced anorexia and starvation or absorption of gram-negative intestinal bacteria and endotoxins through toxin induced gastrointestinal lesions did not account for the enhancing effect of T-2 toxin on resistance to Listeria monocytogenes infection in mice. PMID- 3111317 TI - Nurses, hospitals are linked in vital relationship. PMID- 3111318 TI - Biochemical and cellular actions of membrane lipids. AB - A network of intercellular signals is modulated by eicosanoids derived from arachidonate that can be supplied from either the diet or the membrane lipids. Fatty acid oxygenases controlling the first committed step in the biosynthesis of prostaglandins and leukotrienes are suppressed in normal tissues but are activated by lipid hydroperoxides. Because hydroperoxides are also produced by the action of the oxygenases, they provide positive feedback amplification during eicosanoid biosynthesis. This relationship among membrane lipids, lipid peroxides, and eicosanoids can lead to amplification of the intercellular signals mediated by cytokines and immune globulins in ways that create hyperresponsive states and lead to pathophysiology. PMID- 3111319 TI - Lipid mediators in the control of the ductus arteriosus. AB - The ductus arteriosus (DA) is kept open during fetal development by the continuous relaxant effects of prostaglandins (PG), primarily E2. Although this PGE2 is probably intramurally produced. a subsidiary role for blood-borne PGE2 and PGI2 is not excluded. PGE2 synthetic activity develops early in the developing ductus and is greater in immature than in mature tissues. Ductus sensitivity to PGE2 is greatly diminished after exposure to oxygen. Arachidonic acid (the precursor of PGE2) may inactivates cytochrome P-450, completely reverses the contractile tension of the DA at both low (4 to 12 torr) and high (511 to 712 torr) oxygen tension and is equally effective in the presence and absence of indomethacin. Carbon monoxide-induced relaxation occurs with a PCO/PO2 ratio of 0.27 and is reversed by white light and by monochromatic light with maximal reversal seen at 450 nm wavelength. Both these findings favor involvement of a cytochrome P-450. Metyrapone and phenylimidazole, chemical inhibitors of cytochrome P-450, also relax the ductus. These findings suggest that ductus tone is controlled through the opposing activities of cyclooxygenase and monooxygenase products of AA. The former predominate in the fetus, and the latter at birth when they induce closure/ PMID- 3111320 TI - The relationship of scoring systems and mortality in the surgical intensive care unit. AB - To determine the relationship between severity of illness and mortality, therapeutic intervention score (TISS) and acute physiology score (APS) were determined on admission to the Surgical Intensive Care Unit (SICU). Patients were divided into survivors and nonsurvivors and differences were compared by chi square analysis. The 1524 patients admitted to the SICU during a 12-month period had a mean TISS of 3.03 and a mean APS of 13. The average length of stay (LOS) was 3.75 days. Of the 1524 patients, 97 (6.4%) died. The number of nonsurvivors increased with higher TISS and APS scores (P less than 0.001). There were no deaths in the TISS Category 1 patients or in the APS 0-5 group. Mortality rates dramatically increased with APS greater than 20 (P less than 0.001). There were 1286 patients with APS less than 20, and 24 (2%) of these patients died, whereas 73 (31%) of 238 patients with APS greater than 20 died. Nonsurvivors had a mean TISS of 3.6, mean APS of 27, and LOS of 4.88 days, all of which totals were higher than the survivors' totals. In this study population, risk of death was one in three if the APS was greater than 20. These data indicate that TISS and APS scores are effective means of assessing mortality risk in SICU patients. PMID- 3111321 TI - Evaluation of blood donors with elevated serum alanine aminotransferase levels. AB - We evaluated 100 asymptomatic blood donors with serum alanine aminotransferase (ALT) levels exceeding 0.83 mu kat/L, for evidence of liver disease or risk factors for non-A, non-B hepatitis and followed serum ALT levels for another 6 months. In 92 donors completing the study, ALT elevations occurred once in 33%, intermittently in 36%, persistently in 28%. Twenty-two donors were obese, 5 had clinical and biochemical evidence of alcoholic liver disease, and 45 drank alcohol regularly; 1 had hemochromatosis, and another, myopathy. In 22 no cause for elevated serum ALT levels was found. The presence or absence of risk of acquiring hepatitis did not correlate with the pattern of ALT elevations or the identification of another cause for the elevated ALT levels. In 92 blood donors with an initially elevated ALT level, two-thirds have intermittent or persistent elevations; most approximately 20% have no apparent cause for the elevations other than possible non-A, non-B hepatitis. These findings may be helpful in counseling and following blood donors with elevated ALT levels. PMID- 3111322 TI - Perioperative parenteral nutrition: a meta-analysis. AB - We used a meta-analysis protocol to evaluate the results of 18 controlled trials that measured the effectiveness of perioperative total parenteral nutrition. The pooled results of 11 trials that were randomized or quasi-randomized showed trends suggesting that total parenteral nutrition reduced the risk for complications from major surgery (p = 0.21) and fatalities (p = 0.21). Consideration of these pooled estimates of the effectiveness of this intervention must be offset by the poor quality of the trials' methodologies and the iatrogenic complications (pneumothorax, septicemia) that occurred at a pooled rate of 0.067. Alternately, other design flaws, such as the failure to exclude patients who were not malnourished from the trials, may have limited the ability of these trials to show the effectiveness of total parenteral nutrition. The evidence available up to August 1986 shows that the routine use of perioperative total parenteral nutrition in unselected patients having major surgery is not justified; however, this intervention may be helpful in subgroups of these patients who are at high risk. PMID- 3111323 TI - Perioperative parenteral nutrition. Health and Public Policy Committee, American College of Physicians. PMID- 3111324 TI - Glyburide-induced hypoglycemia and ranitidine. PMID- 3111325 TI - [Permanent mixed states. Discussion of the role of somatic conversion of emotions. Apropos of 2 cases]. PMID- 3111326 TI - The influence of catecholamine systems and thyroid function on the actions of ethanol in long-sleep (LS) and short-sleep (SS) mice. PMID- 3111327 TI - GnRH cell brain grafts. Correction of hypogonadism in mutant mice. PMID- 3111329 TI - Transplantation techniques and the survival of adrenal medulla autografts in the primate brain. PMID- 3111330 TI - Effects of nerve growth factor on the expression of interleukin-2 receptors on cultured human lymphocytes. PMID- 3111328 TI - Voltammetric analysis of nigral graft function. PMID- 3111331 TI - Synthesis of oligosaccharides and peptides using hydrolytic enzymes at decreased water activity. PMID- 3111332 TI - Investigations on the production of fungal amylolytic enzymes by calcium alginate gel immobilized Aspergillus niger. PMID- 3111333 TI - New trends in enzyme recovery. PMID- 3111334 TI - Preparation of bifunctional enzyme complexes by fusion of two genes. PMID- 3111335 TI - Characterization of the beta-glucosidase activity associated with immobilized cellulase of Aspergillus niger. PMID- 3111336 TI - [Effects of mannitol on the fluids of the internal ear. Use in the treatment of deafness]. AB - The action of mannitol upon the inner ear fluids was studied experimentally by means of kinetics of mannitol entry into cochlear perilymph and endolymph in rats. A daily two hours infusion of 10% mannitol induces an osmotic water flow from cochlear fluids toward plasma. Following this therapeutic protocol, progressive, non-tumoral sensorineural hearing loss is enhanced in 32% of the cases. The rate of hearing improvement is larger than 50% in case of Meniere's disease. For sudden hearing loss, 75% of the cases are improved by mannitol, and 92% of the cases when the delay between the hearing loss onset and the mannitol therapy is less than two weeks. Sudden hearing loss should be considered as a sensory emergency. PMID- 3111338 TI - [Toxic methemoglobinemia caused by a gingival lotion containing benzocaine and resorcin]. PMID- 3111337 TI - Radiographic imaging for the cochlear implant. AB - Imaging plays an essential role in evaluating the cochlear implant candidate and the results of implantation. Eighteen candidates for cochlear implantation were reviewed for this study. Fourteen received implants; all but one, intracochlear devices. Based on the trial use of multiple techniques, a protocol has been established for the use of radiography in implant studies. The protocol suggests preoperative high resolution semiaxial computed tomographic scanning, intraoperative anteroposterior transorbital plain films if there is doubt concerning the electrode placement, and postoperative plain films in cases of unexpected poor device performance. In cases with complications, postoperative CT scanning may be required. PMID- 3111339 TI - A randomised comparison of polydioxanone (PDS) and polypropylene (Prolene) for abdominal wound closure. AB - Two hundred and eighty four patients undergoing laparotomy by vertical incision were randomly allocated to closure with interrupted mass sutures of No. 1 polydioxanone (PDS) or No. 1 polypropylene (Prolene). Dehiscence occurred in 0.7% of the PDS group but in 6.4% of the Prolene group (P = 0.018). Wound infection occurred in 8.6% of the PDS group and 15.4% of the Prolene group (P = 0.1). One hundred and ninety patients attended for review at a minimum of one year. Incisional herniation, usually asymptomatic, was present in 11% of each group. Knots were palpable in 2% of the PDS patients but in 12% of the Prolene: wound pain occurred in 12% of the PDS group but in 23% of the Prolene group (P = 0.06). These results suggest that PDS may be useful for abdominal closure. PMID- 3111340 TI - Dangers of placement of narrow bore nasogastric feeding tubes. AB - Three complications of the use of narrow bore nasogastric feeding tubes are described. Clinical tests to determine correct placement are noted to be unreliable and the importance of radiological confirmation is stressed. A number of suggestions are made for safe use of these tubes. PMID- 3111341 TI - Assays for follicle stimulating hormone and luteinising hormone: guidelines for the provision of a clinical biochemistry service. AB - The measurement of serum follicle stimulating hormone (FSH) and luteinising hormone (LH), together with the appropriate sex steroid, is of great value in the investigation of delayed and precocious puberty, hypogonadism, subfertility, polycystic ovarian disease and hypothalamic-pituitary disorders. Dynamic function testing of the hypothalamic-pituitary-gonadal axis should be restricted to a few defined situations. Sequential LH measurements, either in serum or in urine, may be used to time ovulation during artificial insemination or in vitro fertilisation programmes. No special precautions are necessary when sampling for FSH and LH measurement; serum is preferred to plasma and should be stored frozen before assay. Aliquots of timed urine specimens of known volume should be stored frozen without preservative. Gonadotrophin results should be available within 2-3 weeks; laboratories unable to meet this schedule are advised to send their samples to a Regional Centre for assay. Reagents for the radioimmunoassay of FSH and LH are readily available, and standard techniques have been developed for their use. Laboratories using 'in-house' methods should pay particular attention to the matrix used for preparing standard solutions, the purification of radioligands and the optimisation of the separation system. Low cost matched reagents of proven performance are available in kit form from the Chelsea Hospital for Women; several commercial kits are also available, although few are widely used in the UK. The overall performance of laboratories in the UK External Quality Assessment Scheme (EQAS) for FSH and LH has remained steady for several years. Of the 130 participants, only about 15% in each scheme have 'good' performance (cumulative bias less than 10%, plus cumulative variability of bias less than 10%), whilst a similar proportion have 'unacceptable' performance (cumulative bias greater than 20% and/or cumulative variability of bias greater than 25%). The remaining 70% of laboratories have 'adequate' performance but are at risk of producing results that are clinically misleading. Within any one method group, the performance of FSH and LH assays are closely related. Optimal assay performance depends upon sensible laboratory management to ensure skilled operators, a regular programme of reagent/kit renewal, comprehensive internal and external quality assessment, and attention to detail in all aspects of gonadotrophin assay. The working range of each individual assay should be defined and no absolute result reported from outside this range.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3111342 TI - The production and use of monoclonal antibodies to measure apolipoprotein B by a competitive enzyme-linked immunoassay. AB - The production of monoclonal antibodies to human lipoproteins is described. One of these antibodies, which was shown to be specific to apolipoprotein B, was used to develop a competitive enzyme-linked immunoassay for apolipoprotein B in serum samples. The antibody selected recognises apolipoprotein B in both low density and very low density lipoprotein particles, but there is no cross-reactivity with high density lipoprotein. There is no requirement for labelling of antigen or antibody used in the assay, and results obtained correlate well (r = 0.88) with measurements on serum samples using a radial immunodiffusion assay for apolipoprotein B. PMID- 3111343 TI - Comparison of quantitative acid-elution technique and flow cytometry for detecting fetomaternal hemorrhage. AB - A study of the Kleihauer-Betke acid-elution technique for quantitating fetomaternal hemorrhage was performed to assess intra- and inter-technologist accuracy and precision as well as to delineate the statistically valid domain of the test as usually performed. The results were then compared to a parallel study quantitating fetomaternal hemorrhage by flow cytometry. Additionally, a statistical model for estimating efficacy of treatment with Rh immune globulin in the prevention of pregnancy-associated Rh(D) isoimmunization was developed. The results indicate that the acid-elution technique can be performed in a reproducible manner with acceptable accuracy and precision with whole blood fetomaternal hemorrhages 25 ml and higher if a background correction for false positive identification of fetal cells is included. Flow cytometric determination reveals significantly increased accuracy in comparison to the corresponding Kleihauer-Betke results. PMID- 3111344 TI - Immunoglobulin (Gm and Km) allotypes in nine endogamous groups of West Bengal, India. AB - Blood samples from 898 individuals of nine endogamous groups of West Bengal, India were typed for determining the haplotypic structure in the gamma-light chain (Gm) and kappa-light chain (Km) of immunoglobulin (IgG). The Gm haplotype frequencies detected by Glm (1), Glm (2) and G3m (5) markers suggest that in this eastern state of India there is considerable variation of frequencies of the typical Mongoloid haplotype Gm1,5, which shows a high incidence in Rajbanshi, Rabha, Garo and Lodha groups. On the contrary, this haplotype is probably absent in the high caste groups, Rarhi Brahmin and Vaidya, and is relatively infrequent in Jalia Kaibarta, a scheduled caste of the south-western part of the state. The Km1 allele is also high in frequency among Rajbanshi, Rabha, Garo and Munda in comparison with Rarhi Brahmin and Vaidya, suggesting the former four groups' strong Mongoloid affiliation. This survey signifies that there is considerable variation in the extent of Mongoloid admixture in Bengali populations. Such admixture is not restricted in specific social class either. It further demonstrates that heterogeneity of the genetic structure of Bengali populations do not correspond to the present social ranking on the basis of caste hierarchy. PMID- 3111345 TI - Absence seizures in children: clinical and electroencephalographic features. AB - The clinical and electroencephalographic (EEG) features of absence seizures in children were evaluated using EEG frequency modulation radiotelemetry and videotape monitoring. The only seizures evaluated were those with a spike-and wave or multiple spike-and-wave duration lasting at least 3 seconds. A total of 926 absence seizures (426 typical, 500 atypical) were reviewed in 54 patients. Abnormal interictal EEGs, multiple seizure types, mental retardation, or developmental delay were more likely in patients with atypical absence seizures than in patients with typical absence seizures. Both types of absence seizures usually had a clear onset and cessation. Atypical absence seizures lasted significantly longer than did typical absence seizures. Automatisms occurred more frequently in typical absence seizures than in atypical ones, while decreases in postural tone or tonic activity occurred more frequently in atypical absence seizures. Receptive and expressive speech were retained in some patients during both types of seizures. This study demonstrates that typical and atypical absence seizures are not discrete entities but rather form a continuum. No single clinical feature can adequately distinguish the two seizure types. PMID- 3111346 TI - Intergenerational caregiving. PMID- 3111347 TI - Motivation in health behavior: measurement, antecedents, and correlates. AB - Additional reliability, validity, and information on health behavior correlates for a recently developed measure of intrinsic motivation in health behavior are reported. A randomly selected sample of 379 elders responded to a structured interview containing the Health Self-determinism Index (HSDI) and other relevant variables. The overall reliability of the HSDI was supported with an alpha coefficient of 0.78. The multidimensionality of the instrument was reconfirmed through principal components analysis, and factor invariance across study samples was established. The total HSDI and subscale scores were associated with the practice of selected life-style behaviors. The homogeneity of the sample raises significant considerations relative to contextual item sensitivity and sample induced response tendencies. PMID- 3111348 TI - Theoretical perspectives relevant to breast self-examination. AB - The disparity between women's knowledge and performance of breast self examination (BSE) remains an unresolved clinical problem. As a screening behavior, BSE raises interesting issues about motivation. Adequate and useful theoretical perspectives are needed to guide research and to explain BSE performance. This article compares three perspectives of relevance to BSE--the health belief model, self-efficacy theory, and self-regulation theory--and cites empirical support in BSE research for each. A useful theoretical perspective to guide research on BSE is identified. Assumptions within each perspective are also addressed. Finally, future directions for BSE research are proposed. PMID- 3111349 TI - Predictors of breast self-examination practice among elderly women. AB - The purpose of the study presented in this article was to examine predictors of breast self-examination (BSE) practice among elderly female subjects in selected senior citizen centers. The health belief model served as the theoretical framework for the research study. Both the frequency of BSE performance and the technique subjects used to examine their breasts were measured by a questionnaire. Subjects who perceived few barriers to BSE had higher BSE technique scores. The findings also indicated that receiving instruction through a class on BSE was related to improved BSE technique. Perceived susceptibility to breast cancer and perceived benefits of BSE were not found to be significantly predictive of BSE practice. PMID- 3111350 TI - The health belief model as an explanation for breast-feeding practices in a Hispanic population. AB - Pender's modification of the health belief model was used to examine the motivations for breast-feeding in a group of 140 primiparous women along the US Mexican border. The backward elimination technique of linear regression was used to order the variables in the model. The findings indicate that the three components of the health belief model--individual perceptions, modifying factors, and likelihood of action--are useful in predicting health-related outcomes. Each component of the model made an independent contribution to the breast-feeding decision but varied in the strength of the contribution. The only significant interpersonal influence on the feeding decision was that of the husband or partner. More empirical research with the model is necessary, however, in order to develop it as a paradigm for prenatal health. PMID- 3111351 TI - The McGill model of nursing: a practice-derived model. AB - This article describes the salient features of the McGill model of nursing, (ie, health, family, collaboration, and learning), within the health, person, environment, and nursing paradigm. According to the model, the central goal of nursing is to maintain, strengthen, and develop the patient's health by actively engaging him or her in a learning process. Because health is a learned phenomenon and the family is considered the primary socializer in this learning, the family is the focus of nursing. The nurse strives to structure a learning environment that enables the patient to participate as fully as possible. The nurse and patient together set goals and, building on the patient's strengths and resources, devise means of achieving them. PMID- 3111352 TI - Health advocacy for young, low-income, inner-city women. AB - The Urban Women's Health Advocacy Training Project was a university-based demonstration program designed to collect data on the health status of urban women and to test nursing interventions for training community health advocates. Thirty Hispanic and black trainees between 17 and 21 years of age were selected to participate in an eight-week, 20-h/w program emphasizing women's health education, health advocacy skills, and career awareness. This project has many implications for nursing practice with young, inner-city women. Enhancing the self-care and advocacy skills of these women maximizes their potential for use of available health services and their ability to influence the expansion of the services required to meet their own and their families' health care needs. Problems in funding and conducting such demonstration projects are discussed. PMID- 3111353 TI - [Lysosubtilin G10x--a new antimicrobial agent for treatment and prophylaxis. Physico-chemical properties]. AB - Lysosubtilin G10x, a lytic enzyme from Bacillus subtilis SK-52 was studied with respect to its physico-chemical properties such as effect of optimal conditions and stability. The maximum activity of the enzyme was observed in phosphate buffer at a concentration of the buffer mixture equal to 0.004 M, pH 7.2 and the temperature of 37-50 degrees C. Aqueous solutions of lysosubtilin G10x were stable at pH 5-9. The lytic activity of the enzyme aqueous solutions rapidly lowered at a temperature above 50 degrees C. The ions of some metals, especially those of mercury, copper and ferrous iron inhibited the enzyme. Lysis activation was recorded in the presence of surface active substances such as sodium dodecylsuphate, tritone X-100 and certain twins. Comparison of the findings with the results of our previous studies on the lytic properties of enzymes from other strains of B. subtilis showed that irrespective of the strain lysosubtilins were sensitive to changes in the medium ionic strength, they were mostly active in neutral solutions of low ionic strength, their activity was inhibited by heavy metal ions and they were stable within wide ranges of pH. This should be taken into account in practical use of lysosubtilin G10x. PMID- 3111354 TI - Comparative double-blind study of 200- and 400-mg enoxacin given orally in the treatment of acute uncomplicated urethral gonorrhea in males. AB - In a double-blind randomized study, 155 male patients with uncomplicated urethral gonorrhea were given 200 mg (one capsule with 200 mg and one capsule with placebo; n = 77) or 400 mg (two capsules with 200 mg; n = 78) of enoxacin orally. The cure rates in the 200- and 400-mg treatment groups were 90 and 92%, respectively. The enoxacin MIC for the isolated Neisseria gonorrhoeae strains ranged from 0.015 to 0.12 microgram/ml. Postgonococcal urethritis was diagnosed in 29 (42%) patients in the 200-mg treatment group and 19 (26%) patients in the 400-mg treatment group. Side effects (nausea, headache, and vomiting) occurred in 2 (3%) of the 77 patients in the 200-mg treatment group and in 3 (4%) of the 78 patients in the 400-mg treatment group. PMID- 3111355 TI - Therapeutic effects of imipenem-cilastatin on experimental intrauterine infections in rats. AB - The therapeutic effects of imipenem-cilastatin (MK-0787-MK-791) on experimental intrauterine infections in progesterone-treated virgin rats and postpartum rats were studied. The relative efficacy of imipenem-cilastatin for the treatment of such intrauterine infections was compared with that of cefazolin and ampicillin for the treatment of infections caused by Escherichia coli and Streptococcus faecalis, respectively. Treatment with imipenem-cilastatin significantly inhibited the proliferation of E. coli and S. faecalis in uteri, as compared with the proliferation in untreated controls. Cefazolin failed to affect the E. coli infection. With the S. faecalis infection, ampicillin effectively reduced bacterial growth, as compared with that in untreated controls. However, ampicillin was inferior to and comparable to imipenem-cilastatin in progesterone treated virgin rats and postpartum rats, respectively. A further experiment with S. faecalis infections in rats made neutropenic by intraperitoneal injection of cyclophosphamide showed that the therapeutic effectiveness of imipenem-cilastatin was superior to that of ampicillin and was not influenced by neutropenia. Our results suggest that imipenem-cilastatin may be a useful agent for the treatment of obstetric and gynecologic infections. PMID- 3111356 TI - Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa. AB - Two genetically distinct classes of norfloxacin-resistant Pseudomonas aeruginosa PAO4009 mutants were isolated spontaneously. Two norfloxacin resistance genes, nfxA and nfxB, were mapped hex-9001 and leu-9005 and between pro-9031 and ilv 9023, respectively, on the P. aeruginosa PAO chromosome. The nfxA gene was shown to be an allele of nalA by transductional analysis with bacteriophage F116L. The nfxB mutant showed a 16-fold increase in resistance to norfloxacin and a slight increase in resistance to nalidixic acid. The nfxB mutant was unique in that it showed hypersusceptibility to beta-lactam and aminoglycoside antibiotics. This mutant had about a threefold-lower rate of norfloxacin uptake than that of the wild-type strain or nfxA mutant. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane proteins demonstrated the appearance of a 54,000-dalton protein in the nfxB mutant. These findings suggested that the norfloxacin resistance mechanism in the nfxB mutant might be an alteration in outer membrane permeability to norfloxacin. PMID- 3111358 TI - Inducible macrolides-lincosamides-streptogramin B resistance in Bacteroides species. AB - The first evidence is presented for the presence of inducible macrolides lincosamides-streptogramin B resistance in Bacteroides species. Different macrolides induced clindamycin resistance in Bacteroides vulgatus RYC18F6, an erythromycin-resistant and clindamycin-susceptible strain. A study of 144 Bacteroides isolates indicated that erythromycin resistance was linked to diminished clindamycin susceptibility. PMID- 3111357 TI - Synergism of the combinations of imipenem plus ciprofloxacin and imipenem plus amikacin against Pseudomonas aeruginosa and other bacterial pathogens. AB - The combinations of imipenem plus ciprofloxacin and imipenem plus amikacin were investigated for their activity against Pseudomonas aeruginosa and other bacterial pathogens. For imipenem-susceptible P. aeruginosa, synergy of imipenem plus ciprofloxacin and imipenem plus amikacin was observed against 36 and 45% of the strains, respectively. The incidence of synergy against imipenem-resistant isolates of P. aeruginosa was 10% for both combinations. Antagonism was not observed with either combination. PMID- 3111359 TI - Serum bactericidal rate as measure of antibiotic interactions. AB - The serum bactericidal rate (SBR) assay was used to assess the antipseudomonal activity of gentamicin with or without piperacillin. Heat-inactivated donor serum was spiked with gentamicin, piperacillin, or a combination at concentrations representative of levels in serum and tested against five P. aeruginosa strains isolated from blood. The SBR assay was performed as follows: colony counts in test samples (control, gentamicin, piperacillin, and combination) were determined at 0, 2, 4, 6, and 8 h after inoculation of a test strain. Log10 CFU per milliliter was plotted versus time, and linear regression analysis was performed; the slope of the regression line was defined as the SBR. The SBRs of agents alone and in combination were compared statistically. The SBR of gentamicin was dependent on the serum concentration. The combination of gentamicin and piperacillin always resulted in a higher SBR than did either drug alone. However, this difference was not statistically significant for highly gentamicin susceptible strains (MIC, less than or equal to 2 micrograms/ml) until the gentamicin concentration was reduced below the MIC. For a gentamicin-resistant strain (MIC, 8 micrograms/ml), the combination of gentamicin and piperacillin produced mean SBRs similar to that found with gentamicin-susceptible strains. These results provide evidence that the SBR assay may be a useful method of evaluating antibiotic interactions, since it can be done by using serum and since it compares the antibacterial activity of drugs statistically rather than requiring arbitrary criteria to define interactions. PMID- 3111360 TI - Randomized double-blind evaluation of ceftazidime dose ranging in hospitalized patients with cystic fibrosis. AB - Eighty-five patients with cystic fibrosis who were experiencing an acute infectious exacerbation of their disease were randomized in double-blind fashion to receive either 50 or 75 mg of ceftazidime per kg (body weight) per dose administered intravenously every 8 h for 14 days. Three patients were dropped from the study within 4 days of enrollment for reasons unrelated to drug administration. The total daily dose of ceftazidime administered was restricted by protocol design and was independent of the body weight of the patient. Thus, for datum analysis, patients were separated into three ceftazidime dosage groups (denoted as range of milligrams per kilogram per dose): group 1, 22 to 44.5; group 2, 46.3 to 56.6; and group 3, 66.7 to 80.6. Ceftazidime monotherapy had no effect on sputum colony counts for any Pseudomonas cepacia isolate. In contrast, a substantial reduction in Pseudomonas aeruginosa sputum colony counts was observed, and from 19 to 31% of isolates were suppressed greater than or equal to 10(5) CFU/ml after 14 days of therapy. Bacterial resistance in vitro was not observed, although a trend for increasing ceftazidime MICs was observed for group 1 patients (P less than 0.05). Overall, clinical response appeared independent of drug dose, and no relationship could be identified between the reduction in P. aeruginosa sputum colony counts and clinical outcome. Adverse effects of ceftazidime were mild and transient, necessitating drug discontinuation in one patient. These data suggest that the clinical response to ceftazidime in patients with cystic fibrosis may be maximal with 50 mg/kg per dose (150 mg/kg per day) up to a total daily dose of 6 g. PMID- 3111361 TI - Imipenem resistance in Pseudomonas aeruginosa resulting from diminished expression of an outer membrane protein. AB - The mechanism of Pseudomonas aeruginosa resistance to imipenem in five imipenem susceptible clinical isolates and in their resistant counterparts was investigated. The frequency for selecting imipenem-resistant variants ranged from 2.7 X 10(-5) to 2.1 X 10(-8) and was comparable to those for other beta-lactams. Cross-resistance between imipenem and other beta-lactam compounds was not observed. In all imipenem-resistant variants, induction of chromosomal beta lactamase by imipenem was markedly diminished compared with that in the susceptible parent strain. This was not the case for other inducers such as ampicillin or cefoxitin, suggesting an impaired uptake of imipenem as an explanation for resistance. Analysis of the outer membrane proteins revealed a marked decrease of either a 46- or a 45-kilodalton protein. The lipopolysaccharide of the outer membrane in the imipenem-resistant variants was not altered. PMID- 3111362 TI - Failure to demonstrate a consistent in vitro bactericidal effect of trimethoprim sulfamethoxazole against enterococci. AB - Controversy exists as to the in vitro and in vivo activities of trimethoprim sulfamethoxazole (TMP-SMX) against enterococci. In this study, we investigated the in vitro activity of TMP-SMX in the type of Mueller-Hinton broth previously reported to give the lowest MICs and MBCs with enterococci. In all instances, MICs were less than or equal to 0.5 microgram/ml. The majority of tests showed MBCs of greater than 32 micrograms/ml, although there was some effect from varying the inoculum and the length of incubation after subculturing. Minor differences were noted when tests were repeated and between the results from microdilution and macrodilution tests and those obtained by the time-kill method. These results, as well as other reports, suggest that TMP-SMX should not be considered a reliable bactericidal agent against enterococci. PMID- 3111363 TI - Identification of O-methylsterigmatocystin as an aflatoxin B1 and G1 precursor in Aspergillus parasiticus. AB - An isolate of Aspergillus parasiticus CP461 (SRRC 2043) produced no detectable aflatoxins, but accumulated O-methylsterigmatocystin (OMST). When sterigmatocystin (ST) was fed to this isolate in a low-sugar medium, there was an increase in the accumulation of OMST, without aflatoxin synthesis. When radiolabeled [14C]OMST was fed to resting mycelia of a non-aflatoxin-, non-ST-, and non-OMST-producing mutant of A. parasiticus AVN-1 (SRRC 163), 14C-labeled aflatoxins B1 and G1 were produced; 10 nmol of OMST produced 7.8 nmol of B1 and 1.0 nmol of G1, while 10 nmol of ST produced 6.4 nmol of B1 and 0.6 nmol of G1. A time course study of aflatoxin synthesis in ST feeding experiments with AVN-1 revealed that OMST is synthesized by the mold during the onset of aflatoxin synthesis. The total amount of aflatoxins recovered from OMST feeding experiments was higher than from experiments in which ST was fed to the resting mycelia. These results suggest that OMST is a true metabolite in the aflatoxin biosynthetic pathway between sterigmatocystin and aflatoxins B1 and G1 and is not a shunt metabolite, as thought previously. PMID- 3111364 TI - Coagglutination and enzyme capture tests for detection of Escherichia coli beta galactosidase, beta-glucuronidase, and glutamate decarboxylase. AB - Polyclonal antibodies to Escherichia coli beta-galactosidase, beta-glucuronidase, and glutamate decarboxylase were used in coagglutination tests for identification of these three enzymes in cell lysates. Enzyme capture assays were also developed for the detection of E. coli beta-galactosidase and beta-glucuronidase. The enzymes were released by using a gentle lysis procedure that did not interfere with antibody-enzyme interactions. All three enzymes were detected in 93% (51 of 55) of the E. coli strains tested by coagglutination; two of the three enzymes were identified in the remaining 7%. Of 42 non-E. coli tested by coagglutination, only four nonspecifically agglutinated either two or three of the anti-enzyme conjugates. Thirty-two (76%) non-E. coli isolates were negative by coagglutination for all three enzymes. The enzyme capture assay detected the presence of beta-galactosidase in seven of eight and beta-glucuronidase in all eight strains of E. coli tested. Some strains of beta-galactosidase-positive Citrobacter freundii and Enterobacter cloacae were also positive by the enzyme capture assay, indicating that the antibodies were not entirely specific for E. coli beta-galactosidase; however, five other gas-positive non-E. coli isolates were negative by the enzyme capture assay. The coagglutination tests and enzyme capture assays were rapid and sensitive methods for the detection of E. coli beta galactosidase, beta-glucuronidase, and glutamate decarboxylase. PMID- 3111365 TI - Extensive degradation of Aroclors and environmentally transformed polychlorinated biphenyls by Alcaligenes eutrophus H850. AB - We have isolated and characterized a strain of Alcaligenes eurtrophus, designated H850, that rapidly degrades a broad and unusual spectrum of polychlorinated biphenyls (PCBs) including many tetra- and pentachlorobiphenyls and several hexachlorobiphenyls. This strain, which was isolated from PCB-containing dredge spoils by enrichment on biphenyl, grows well on biphenyl and 2-chlorobiphenyl but poorly on 3- and 4-chlorobiphenyl. Capillary gas-chromatographic analysis showed that biphenyl-grown resting cells of H850 degraded the components of 38 of the 41 largest peaks of Aroclor 1242 and 15 of the 44 largest peaks of Aroclor 1254, resulting in an overall reduction of PCBs by 81% for Aroclor 1242 (10 ppm) and 35% for Aroclor 1254 (10 ppm) in 2 days. Furthermore, H850 metabolized the predominantly ortho-substituted PCB congeners that resulted from the environmental transformation of the more highly chlorinated congeners of Aroclor 1242 by the upper Hudson River anaerobic meta-, para-dechlorination agent system C (J. F. Brown, R. E. Wagner, Jr., D. L. Bedard, M. J. Brennan, J. C. Carnahan, R. J. May, and J. J. Tofflemire, Northeast Environ. Sci. 3:167-179, 1984). The congener selectivity patterns indicate that a two-step process consisting of anaerobic dechlorination followed by oxidation by H850 can effectively degrade all of the congeners in Aroclor 1242 and possibly all those in Aroclor 1254. PMID- 3111366 TI - Evidence for novel mechanisms of polychlorinated biphenyl metabolism in Alcaligenes eutrophus H850. AB - Previous studies indicated that Alcaligenes eutrophus H850 attacks a different spectrum of polychlorinated biphenyl (PCB) congeners than do most PCB-degrading bacteria and that novel mechanisms of PCB degradation might be involved. To delineate this, we have investigated the differences in congener selectivity and metabolite production between H850 and Corynebacterium sp. strain MB1, an organism that apparently degrades PCBs via a 2,3-dioxygenase. H850 exhibited a superior ability to degrade congeners via attack on 2-, 2,4-, 2,5-, or 2,4,5 chlorophenyl rings in PCBs but an inferior ability to degrade congeners via attack on a 4-chlorophenyl ring. Reactivity preferences were also reflected in the products formed from unsymmetrical PCBs; thus MB1 attacked the 2,3 chlorophenyl ring of 2,3,2',5'-tetrachlorobiphenyl to yield 2,5-dichlorobenzoic acid, while H850 attacked the 2,5-chlorophenyl ring to yield 2,3-dichlorobenzoic acid and a novel metabolite, 2',3'-dichloroacetophenone. Furthermore, H850 oxidized 2,4,5,2',4',5'-hexachlorobiphenyl, a congener with no adjacent unsubstituted carbons, to 2',4',5'-trichloroacetophenone. The atypical congener selectivity pattern and novel metabolites produced suggest that A. eutrophus H850 may degrade certain PCB congeners by a new route beginning with attack by some enzyme other than the usual 2,3-dioxygenase. PMID- 3111367 TI - Occurrence of Staphylococcus aureus and Pseudomonas aeruginosa in Israeli coastal water. AB - The occurrence of Pseudomonas aeruginosa and coagulase-positive Staphylococcus aureus in seawater from beaches of central Israel was investigated from June 1983 until June 1985. P. aeruginosa was monitored in 652 samples of seawater from 34 beaches, and S. aureus was monitored in 628 samples. P. aeruginosa was found in 44.8% of samples (6.5% with 1 bacterium per 100 ml of water), and S. aureus was recovered from 60.7% of samples (5.3% with 1 organism per 100 ml), compared with 91.6% of samples with total coliforms (TC) and 82.2% with fecal coliforms (FC). The correlation between the presence of P. aeruginosa to that of TC and FC was 99.1 and 98.3%, respectively, while S. aureus was found in 4.3 and 8% of samples where TC and FC, respectively, were absent. Monitoring of S. aureus as a supplementary indicator in populated beaches is recommended because it will add valuable information on the sanitary quality of the seawater. PMID- 3111368 TI - Stimulation by Hyphopichia burtonii and Bacillus amyloliquefaciens of aflatoxin production by Aspergillus flavus in irradiated maize and rice grains. AB - Aspergillus flavus was grown on maize and rice extract agars and on irradiated viable cracked maize and rice grains, either in pure culture or in dual culture with wild strains of either Hyphopichia burtonii or Bacillus amyloliquefaciens. Aflatoxin production by A. flavus and its growth and interactions with the other microorganisms were studied at three water activities (aw) (0.98, 0.95, and 0.90) and two temperatures (25 and 16 degrees C). Both H. burtonii and B. amyloliquefaciens markedly stimulated growth and aflatoxin production by A. flavus on cracked maize, especially at 25 degrees C and 0.95 and 0.98 aw. No aflatoxin was detected in pure cultures of A. flavus on cracked rice after 12 days of incubation at 25 degrees C, but some was produced by mixed cultures at 16 degrees C and 0.98 aw. The morphological interactions among A. flavus, H. burtonii, and B. amyloliquefaciens were also examined on maize and rice extract agars under similar controlled conditions. PMID- 3111369 TI - Comparison of media and methods for detecting and enumerating Listeria monocytogenes in refrigerated cabbage. AB - Direct plating, selective enrichment, and cold enrichment followed by secondary selective enrichment procedures were compared for detecting and enumerating Listeria monocytogenes in chopped cabbage stored at 5 degrees C for up to 64 days. Addition of Fe3+ to solid media enhanced detection of the organism. Cold enrichment (5 degrees C) in nutrient broth and brain heart infusion broth followed by secondary enrichment (48 h, 30 degrees C) in Trypticase soy-yeast extract-antibiotic broth and thiocyanate-nalidixic acid broth and plating on selective agar media (Doyle and Schoeni selective enrichment agar [minus acriflavin hydrochloride, supplemented with 5 micrograms of Fe3+/ml] and McBride Listeria agar) resulted in the detection of highest populations. PMID- 3111370 TI - Nucleotide and deduced amino acid sequences of the Staphylococcus aureus phospho beta-galactosidase gene. AB - We sequenced the Staphylococcus aureus phospho-beta-galactosidase gene. The protein product of this gene consisted of 470 amino acids, giving a molecular weight of 54,557. This gene appears to be transcribed as the terminal sequence on a polycistronic message. PMID- 3111371 TI - Potential for transduction of plasmids in a natural freshwater environment: effect of plasmid donor concentration and a natural microbial community on transduction in Pseudomonas aeruginosa. AB - Transduction of Pseudomonas aeruginosa plasmid Rms149 by the generalized transducing bacteriophage phi DS1 was shown to occur during a 9-day incubation of environmental test chambers in a freshwater reservoir. Plasmid DNA was transferred from a nonlysogenic plasmid donor to a phi DS1 lysogen of P. aeruginosa that served both as the source of the transducing phage and as the recipient of the plasmid DNA. When the concentration of donors introduced into the chambers was varied while the recipient concentration in each chamber was at a level equivalent to natural concentrations of P. aeruginosa, the concentration of plasmid-containing donor cells introduced was shown to affect the frequency of transduction significantly. Transduction was observed both in the absence and in the presence of the natural microbial community. The presence of the natural community resulted in a rapid decrease in the numbers of the introduced donors and recipients and a decrease in the number of transductants recovered. These results demonstrate the potential for naturally occurring transduction in aquatic environments and indicate that donor load may be an important parameter in assessing this potential. PMID- 3111372 TI - Comparative survival of antibiotic-resistant and -sensitive fecal indicator bacteria in estuarine water. AB - The survival of antibiotic-resistant and -sensitive strains of Escherichia coli, Enterococcus faecalis, Enterococcus faecium, Streptococcus equinus, and two environmental isolates, AP17 and AQ62, was examined in estuarine water. Each strain was rendered resistant to a combination of two antibiotics by serial passage in increasing concentrations of antibiotics. Cultures were incubated in filter-sterilized estuarine water for up to 7 days. Recovery was assessed by examining colony-forming ability on media with and without antibiotics. None of the antibiotic-resistant forms survived longer than its antibiotic-sensitive counterpart in estuarine water. Three of the resistant strains died off more rapidly than the antibiotic-sensitive wild type. Survival of the test bacteria in estuarine water was as follows: sensitive and resistant AQ62, resistant Escherichia coli less than sensitive Escherichia coli less than resistant AP17 less than resistant Enterococcus faecium less than sensitive AP17, sensitive and resistant S. equinus less than sensitive and resistant Enterococcus faecalis, sensitive Enterococcus faecium. The results supported the suggestion that fecal entercocci may serve as better indicators of fecal pollution than Escherichia coli in marine ecosystems. Moreover, the results indicated that the use of antibiotic-resistant mutants to follow the fate of bacteria in the environment is inappropriate without adequate studies to ensure that resistant and wild-type strains react similarly to environmental stressors. PMID- 3111373 TI - Aflatoxin contamination of maize in flooded areas of Bhagalpur, India. AB - Maize in flood-affected areas in the Bhagalpur district of India in 1985 demonstrated heavy infestations of Aspergillus flavus and aflatoxins. Sixty samples collected from various field lots were positive in the bright greenish yellow fluorescence test. However, only 42 of those samples were found to be contaminated with deleterious levels of aflatoxins. Factors affecting aflatoxin contamination are discussed. PMID- 3111375 TI - Structural studies on neonatal rat liver glycogen synthase: a comparison between adult and newborn synthase phosphopeptides. AB - Liver glycogen synthase has been isolated from newborn rats and phosphorylated in vitro with the catalytic subunit of cAMP-dependent protein kinase. The isolated newborn synthase b is dependent upon Glc 6-P for activity, like adult synthase b, but has a high affinity toward Glc 6-P, unlike adult synthase b but like adult synthase a. Phosphorylation decreases the newborn synthase affinity toward Glc 6 P to the same value as adult synthase b. A comparison of adult and newborn synthase 32Pi-labeled trypsin and chymotrypsin peptide fragments by sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that the newborn synthase has structural properties significantly different from the adult enzyme. Thus, a fetal isozyme of synthase in the newborn rat could account, in part, for the difference in catalytic properties, relative to adult synthase. PMID- 3111374 TI - Metabolism of monoterpenes: demonstration of the hydroxylation of (+)-sabinene to (+)-cis-sabinol by an enzyme preparation from sage (Salvia officinalis) leaves. AB - A microsomal preparation from the epidermis of Salvia officinalis leaves catalyzed the NADPH- and O2-dependent hydroxylation of the monoterpene olefin (+) sabinene to (+)-cis-sabinol. The reaction catalyzed is a key step in the biosynthesis of C3-oxygenated thujane monoterpenes, and the hydroxylase is highly specific for (+)-sabinene as substrate. The hydroxylase from leaf homogenates was solubilized and characterized with regard to reaction conditions, inhibitors, and activators. Activity was partially inhibited by rabbit anti-rat cytochrome P-450 and by CO, and the latter inhibition was reversed by 450 nm light. A CO difference spectrum and type I substrate binding spectrum were obtained. The hydroxylase meets most of the established criteria for a cytochrome P-450 dependent mixed function oxygenase and represents one of very few enzyme systems of this type to be isolated from leaves of a higher plant. PMID- 3111376 TI - Reactions of O-acyl-L-serines with tryptophanase, tyrosine phenol-lyase, and tryptophan synthase. AB - The reactions of tryptophanase, tyrosine phenol-lyase, and tryptophan synthase with a new class of substrates, the O-acyl-L-serines, have been examined. A method for preparation of O-benzoyl-L-serine in high yield from tert. butyloxycarbonyl (tBoc)-L-serine has been developed. Reaction of the cesium salt of tBoc-L-serine with benzyl bromide in dimethylformamide gives tBoc-L-serine benzyl ester in excellent yield. Acylation with benzoyl chloride and triethylamine in acetonitrile followed by hydrogenolysis with 10% palladium on carbon in trifluoroacetic acid gives O-benzoyl-L-serine, isolated as the hydrochloride salt. O-Benzoyl-L-serine is a good substrate for beta-elimination or beta-substitution reactions catalyzed by both tryptophanase and tyrosine phenol-lyase, with Vmax values 5- to 6-fold those of the physiological substrates and comparable to that of S-(o-nitrophenyl)-L-cysteine. Unexpectedly, O-acetyl-L serine is a very poor substrate for these enzymes, with Vmax values about 5% of those of the physiological substrates. Both O-acyl-L-serines are poor substrates for tryptophan synthase, measured either by the synthesis of 5-fluoro-L tryptophan from 5-fluoroindole and L-serine catalyzed by the intact alpha 2 beta 2 subunit or by the beta-elimination reaction catalyzed by the isolated beta 2 subunit. With all three enzymes, the elimination of benzoate appears to be irreversible. These results suggest that the binding energy from the aromatic ring of O-benzoyl-L-serine is used to lower the transition-state barrier for the elimination reactions catalyzed by tryptophanase and tyrosine phenol-lyase. Our findings support the suggestion (M. N. Kazarinoff and E. E. Snell (1980) J. Biol. Chem. 255, 6228-6233) that tryptophanase undergoes a conformational change during catalysis and suggest that tyrosine phenol-lyase also may undergo a conformational change during catalysis. PMID- 3111377 TI - Subparticles of Anabaena phycobilisomes. II. Molecular assembly of allophycocyanin cores in reference to "anchor" protein. AB - Entire phycobilisomes (PBS) and two derived particles, whole allophycocyanin (APC) cores and the far-red-emitting fragment of APC cores (14.5 S APC), all containing the 115-kDa polypeptide ("anchor protein"), were compared for the readiness with which the 115-kDa protein could be modified chemically, be degraded by chymotrypsin, and react with the anti-115-kDa serum. The 115 kDa in PBS and the whole APC cores were digested slightly by chymotrypsin and did not react with anti-115-kDa IgG. In contrast, the 115 kDa in 14.5 S APC was digested to 42 kDa and showed a positive reaction with anti-115-kDa IgG. Reconstitution of APC cores from 14.5 S APC and APC trimers was inhibited by the anti-115-kDa IgG, and APC particles with partly digested 115-kDa cannot reconstitute APC cores. These results imply that 115 kDa is embedded mostly inside PBS and is involved more in the maintenance of the molecular assembly of APC cores than in the "anchoring" of PBS to thylakoid. The PBS from Anabaena variabilis (M3) have an APC core larger than those of other PBS and show atypical morphology consisting of five APC discs. They have a polypeptide (115 kDa) that is significantly longer than the corresponding polypeptides (around 95 kDa) of other blue-green algae. This can be interpreted by assuming a relationship between the size of APC cores and the length of the polypeptide. PMID- 3111378 TI - Glyphosate sensitivity of 5-enol-pyruvylshikimate-3-phosphate synthase from Bacillus subtilis depends upon state of activation induced by monovalent cations. AB - The 5-enol-pyruvylshikimate-3-phosphate (EPSP) synthase from Bacillus subtilis was activated by monovalent cations, catalytic activity being negligible in the absence of monovalent cations. The order of cation effectiveness (NH4+ greater than K+ greater than Rb+ greater than Na+ = Cs+ = Li+) indicated that the extent of activation was directly related to the unhydrated cation radius. Ammonium salts, at physiological concentrations, were dramatically more effective than other cations. Activation by ammonium was instantaneous, was not influenced by the counter ion, and gave a hyperbolic saturation curve. Hill plots did not show detectable cooperativity in the binding of ammonium. Double-reciprocal plots indicated that ammonium increases the maximal velocity and decreases the apparent Michaelis constants of EPSP synthase with respect to both phosphoenol pyruvate (PEP) and shikimate 3-phosphate (S3P). A direct relationship between sensitivity to inhibition by glyphosate and the activation state of EPSP synthase was demonstrated. Hill plots indicated a single value for glyphosate binding throughout the range of ammonium activation. Double-reciprocal plots of substrate saturation data obtained with ammonium-activated enzyme in the presence of glyphosate showed glyphosate to behave as a competitive inhibitor with respect to PEP and as a mixed-type inhibitor relative to S3P. The increased glyphosate sensitivity of ammonium-activated EPSP synthase is attributed to a lowering of the inhibitor constant of glyphosate with respect to PEP. Erroneous underestimates of sensitivities of some bacterial EPSP synthases to inhibition by glyphosate may result from failure to recognize cation requirements of EPSP synthases. PMID- 3111379 TI - [Functional and biochemical characterization of interleukin 2 receptor-associated molecules]. AB - The interaction of interleukin 2 and the interleukin 2 receptor plays a crucial role in T cell proliferation. Unlike other growth factor receptors, the interleukin 2 receptor has a rudimentary intracytoplasmic portion that is too short to mediate any kinase activity. There are two classes of interleukin 2 receptor, with either high or low affinity. Only the high-affinity receptor mediates interleukin 2-driven transmembrane signal transduction. However, the mechanisms that control the affinity of the receptor and mediate transmembrane signal transduction are unknown. We report here that the rat interleukin 2 receptor has an associated molecule. The association of the rat interleukin 2 receptor with rat lymphocyte activation antigen, 5C6-F4 was demonstrated using the chemical cross-linking reagent, DTSSP. It is likely that the formation of a complex between the receptor and 5C6-F4 is important for the generation of the functional interleukin 2 receptor. PMID- 3111380 TI - [Futraful and UFT, their metabolic characteristics]. AB - Investigations were made in human on the metabolism of Futraful (FT) and UFT (combination of uracil and FT), both of which are anticancer agents of pyrimidine metabolism antagonist. As a result, it was demonstrated that from the metabolic view point, those drugs essentially have a tumor-selective toxicity. Next, the mechanism of the superior clinical anticancer effect of UFT, compared to FT, was investigated enzymatically, showing the inhibitory effect of uracil on the degradation of 5-fluorouracil generated from FT in the organs and tumor tissues. Discussions were also made for the further development of fluoropyrimidines. PMID- 3111381 TI - [FO-152]. AB - 5'-O-(L-valyl)-5-fluorouridine hydrochloride (FO-152) is a derivative of 5 fluorouridine. In preclinical studies, FO-152 has demonstrated more favorable antitumor effect with greater therapeutic index compared with the parent compound, 5-fluorouridine. A phase I study was performed in 38 cases with advanced cancer. Myelosuppression was dose limiting, with leukopenia more pronounced than thrombocytopenia. Other side effects included mild hot feeling of the body during infusion and slight G.I. toxicities. Clinical responses were seen in patients with adenocarcinoma of the stomach, lung, etc. FO-152 has major advantages over 5-fluorouridine in terms of reduced toxicity. The recommended phase II dose for patients with solid tumors is 250 mg/m2 X 1, or 35 mg/m2 X 5 consecutive days with a 4-week rest, provided there is reversal of drug related myelosuppression. PMID- 3111382 TI - [Neo-adjuvant chemotherapy with UFT and adriamycin in head and neck cancer]. AB - Thirty-one patients with head and neck cancer were administered pretreatment induction chemotherapy (so-called neo-adjuvant chemotherapy) consisting of a UFT and ADM combination. The chemotherapy consisted of ADM (0.5 mg/kg b.w.) once a week up to 3 times, and UFT (600 mg/day) every day for 20 days. Overall response rate was 37.9% (11/31), and 1 CR and 10 PR were obtained. After definitive treatment, the primary control rate was 80.6% (25/31). Sixteen primary lesions in the 31 patients were classified according to Shimosato's grading system into 1 grade IV, 5 grade III and 10 grade II b a-I. Lymph-node metastases in 5 cases were also classified. The grading of lymph-node metastases was lower than that of the primary lesions. PMID- 3111383 TI - [A study on UFT concentration in tissues and serum of patients with malignant gynecologic tumors following oral administration]. AB - UFT was orally given at a dose of 200 mg twice a day to seven female patients with malignant gynecological tumors. Measurements of blood and tissue concentrations of tegafur (TF), fluorouracil (FU) and uracil (U) showed that the concentrations of both FU and U were clearly increased. The ratio of concentration in the tumor to that in peripheral blood was 9.3, while that of the concentration in the internal iliac lymph nodes to that in the internal iliac artery was 11.2. The changes in blood levels of the three compounds were determined one and five days after UFT administration. There was a distinct difference in the blood levels of the drug among TF, FU and U. TF reached its peak concentration two hours after breakfast and four hours after supper; both FU and U reached their peak concentrations two hours after breakfast and one hour after supper. Furthermore, TF showed a tendency to accumulate after continuous administration, but this was not the case with FU or U. These findings suggest that even during continuous administration, the blood level of FU remains low. PMID- 3111384 TI - [Inhibition of the growth of a murine transplantable tumor, colon 26, by the prostaglandin synthetase inhibitor, indomethacin]. AB - Cancer cells and macrophages produce large amounts of prostaglandin (PG) E2, which suppress cellular immune r action in tumor-bearing individuals. These findings raised a possibility that PG synthetase inhibitor can restore the immune reactivity against tumors. The anti-tumor activity of indomethacin, a potent PG synthetase inhibitor, by oral administration of 0.002% water solution as drinking water from the day 0 or 7 days after tumor transplantation was investigated in BALB/c or CDF1 (BALB/c X DBA/2) mice implanted subcutaneously with colon carcinoma 26 (10(6) cells) as a series of model studies for cancer treatment. The treatment with indomethacin substantially 1) inhibited the tumor growth, 2) prolonged the survival time, 3) caused a regression and disappearance of tumor with some cured mice and 4) reduced the levels of PGE2 and ornithine decarboxylase activity, a first rate limiting enzyme of polyamine synthesis in tumor tissue. Those anti-tumor activities were 5) reduced by a concomitant administration of PGE2 and 6) increased by a combined administration of an immunopotentiating agent, Picibanil (OK-432). The results indicate that indomethacin inhibited the synthesis of PGE2 in the tumor tissue, which suppress the non-specific cellular immune reaction against tumor cells, resulting in the regression and disappearance of tumor. PG synthetase inhibitor may be effective also against human cancer. PMID- 3111385 TI - [Morphological changes in rabbit pleura induced by Lactobacillus casei (LC9018)]. PMID- 3111387 TI - Neurofibromatosis. The importance of localized or otherwise atypical forms. PMID- 3111386 TI - [Recent advanced studies on mitomycins, antitumor activity and mode of action]. AB - Mitomycin C (MMC) showed a wide antitumor spectrum with regression of various tumors and the optimal schedule of a single or intermittent administration against human tumor cells xenografted to nude mice, confirming the early reports obtained in rodent tumor system. The sensitivity of various human tumors xenografted to nude mice has been tested to antitumor agents to establish the system which could select the clinically active drugs. The effectiveness of MMC against human stomach cancers xenografted to nude mice clearly correlated to the clinical effect of MMC against gastric cancer. The covalent cross-link adducts between MMC and DNA were isolated in the bioreductive system of NADPH-cytochrome C reductase and NADPH, and the major monoadduct was determined as N2-(2'' beta 7' diaminomitosen-1''-alpha yl)-2'-deoxyguanine. Importantly, bisadduct was isolated, and the structure was determined by spectroscopic method. DNA-DNA cross link formation was shown by alkaline elution in cells treated with MMC. The activation of MMC has been characterized by the two electron transfer process, however, the one electron transfer process was proposed by electrochemical analysis. MMC was effective against hypoxic cells. Several cell lines resistant to MMC were isolated, and some MMC derivatives showed in vivo and in vitro anti tumor activity against these resistant cells. PMID- 3111388 TI - Segmental neurofibromatosis. AB - Three cases of segmental neurofibromatosis (NF) and one case of bilateral segmental NF are described. Previous cases described as segmental NF are reviewed and evaluated in light of Riccardi's rigid definition of segmental NF. The previously reported cases are then placed in four subgroups. Segmental NF may evolve into a generalized form over time. Also, this disorder may occur in a heritable manner, Genetic counseling of affected individuals must include these facts. PMID- 3111389 TI - Pseudomonas infections in cystic fibrosis. PMID- 3111390 TI - The effects of polychlorinated biphenyls and methylmercury, singly and in combination, on mink. I: uptake and toxic responses. PMID- 3111391 TI - The effects of polychlorinated biphenyls and methylmercury, singly and in combination on mink. II: Reproduction and kit development. PMID- 3111392 TI - Effects of chronic polychlorinated biphenyls exposure on reproductive success of white-footed mice (Peromyscus leucopus). PMID- 3111393 TI - Maximal oxygenation of dilute blood cardioplegic solution. AB - The content of dissolved O2 (the major source of O2 for the myocardium) of dilute blood cardioplegic solution (dBCS) varied widely when oxygenated at 4 degrees C by surface flow of O2 in a Bentley BCR-3500 cardiotomy reservoir. We have modified the system to consistently deliver maximally oxygenated dBCS to the heart. Laboratory studies indicated that bubbling O2 through a 16-gauge intravenous catheter in a central Luer-Lok port of the cardiotomy reservoir provided contents of dissolved O2 that were consistently near maximal. We then studied 17 patients in the operating room. The first 6 patients received dBCS oxygenated with 100% O2 with a high dissolved O2 content of 3.2 +/- 0.2 ml/dl. However, the pH of the dBCS became highly alkaline (7.83 +/- 0.11 at 37 degrees C). Therefore, in the remaining 11 patients, 2% CO2 was added to the O2. The dissolved O2 content remained high (3.3 +/- 0.1 ml/dl), and the pH was in a more physiological range (7.35 +/- 0.09 at 37 degrees C). We conclude that consistently maximal oxygenation of a dBCS at a more physiological pH can be achieved by this method. PMID- 3111394 TI - Seminal plasma hormone profile in infertile men with and without varicocele. AB - Seminal plasma FSH, LH, prolactin, testosterone, and oestradiol were estimated in 41 infertile men with varicocele and 45 infertile men without varicocele who failed to impregnate their wives after 2 years of marriage and 30 fertile men. There was significant elevation of FSH in the seminal plasma of the infertile men with varicocele compared with the seminal plasma of the other infertile and fertile men. Seminal LH and prolactin values were similar in both infertile groups but significantly higher than in the fertile men. Testosterone and oestradiol levels in the seminal plasma of infertile men with varicocele were lower than in the fertile and the other infertile males. Finding that both steroids were decreased in infertile men with varicocele could explain disturbed function of spermatozoa in men with varicocele. Further analysis will elucidate the importance of these hormone findings in the seminal plasma of infertile men with varicocele. PMID- 3111395 TI - Stability of rat pituitary gonadotropins during nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AB - 125I-(rLH) and 125I-(rFSH) were dissolved in sample buffer containing 0-0.1% (SDS) and subjected to SDS-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions at room temperature. 125I-rFSH migrated as a single band, while 125I-rLH migrated as two bands corresponding to rLH and rLH subunits suggesting partial dissociation. The dissociation of rLH increased as the concentration of SDS in the sample buffer was increased. However, electrophoresis of 125I-rLH at 4 degrees C under nonreducing conditions caused minimal dissociation. These data suggest that substantial dissociation of rLH, but not rFSH, occurs during nonreducing SDS-PAGE at room temperature and running the gels at 4 degrees C minimizes the dissociation of rLH. PMID- 3111396 TI - Viral hepatitis. A population-based study in Rochester, Minn, 1971-1980. AB - The incidence of acute viral hepatitis among Rochester, Minn, residents 1971-1980 was 28.6 per 100,000 person-years (p-y) (age- and sex-adjusted to the 1980 white population in the United States). The adjusted incidence of hepatitis B (12.9 per 100,000 p-y) was somewhat less than for hepatitis non-B (15.6 per 100,000 p-y). Each type was more frequent among young adults, especially males. The incidence of hepatitis was greater among those employed in the health service industry than among nonmedical employees (53.4 vs 20.0 per 100,000 p-y). Medical employees had nearly a fivefold increased incidence of hepatitis B and a twofold increased incidence of hepatitis non-B. Exposure to known hepatitis cases was common, but other possible causative factors were not frequent. In this midwestern community, the incidence of acute viral hepatitis is substantial, with medical employees at significantly increased risk. PMID- 3111397 TI - Modeling decisions to use tube feeding in seriously ill patients. AB - Clinical decisions to use life-sustaining technologies, such as tube feeding in seriously ill patients, depend on many important factors. Using case simulations, we analyzed the decisions of students, housestaff, and faculty of Temple University School of Medicine, Philadelphia, to use tube feeding in seriously ill patients. Although patient preference was the most important factor for most respondents, we observed three different patterns of decision strategies. Those in the first group, the autonomists (34% of respondents), considered only patient preference; those in the second group, the mixed strategists (56% of respondents), included patient preference among other important factors; and those in the third group, the paternalists (10% of respondents), used factors other than patient preference. More experienced clinicians and those individuals who believed tube feeding represented an extraordinary level of care were significantly less likely to begin tube feeding in the case simulations. Description of these individual decision strategies and elucidation of the important physician characteristics can help identify the potential ethical dilemmas in these different clinical decisions. PMID- 3111398 TI - Synthetic human calcitonin in refractory Paget's disease of bone. AB - Fourteen patients with symptomatic and active Paget's disease of bone who had demonstrated resistance to parenteral synthetic salmon calcitonin, oral disodium etidronate, or both in combination were treated with parenteral synthetic human calcitonin. Eleven patients (79%) demonstrated clinical and chemical improvement for up to five years. Two patients received additional benefit with combined synthetic human calcitonin and etidronate disodium. PMID- 3111399 TI - Euthyroid hyperthyroxinemia and inappropriate secretion of thyrotropin. Recognition and diagnosis. AB - Various disease states associated with euthyroid hyperthyroxinemia and inappropriate thyrotropin secretion are becoming increasingly recognized. These diagnoses were established in six (11%) of 57 patients referred for evaluation of elevated free thyroxine index over an 11-month period. Failure to separate these entities from primary thyrotoxicosis may result in unnecessary thyroid ablative therapy and subsequent clinical confusion. Several illustrative patient summaries are presented to outline an approach to this clinical challenge. PMID- 3111400 TI - [Hypophosphatasia: Physiopathological basis and clinical characteristics]. PMID- 3111401 TI - [The use of nuclear magnetic resonance in the study of temporomandibular joint pathology]. PMID- 3111402 TI - [Nonsteroidal anti-inflammatory agents in the treatment of periodontal disease. Review of the literature]. PMID- 3111403 TI - [Dentin hypersensitivity]. PMID- 3111405 TI - [Suggestions for the application of the British model to the organization of the Public Dental Service in Spain]. PMID- 3111404 TI - [Microstructural analysis of fissure sealing resins]. PMID- 3111406 TI - [Angular stomatitis. Apropos of a clinical case]. PMID- 3111407 TI - [Clinical procedures in oral rehabilitation with fixed dentures over osseointegrated implants]. PMID- 3111409 TI - [Critical evaluation of the work on the chronology of the eruption of the deciduous teeth]. PMID- 3111408 TI - [Diagnosis of cracked tooth syndrome]. PMID- 3111411 TI - [Growth and interceptive dentistry]. PMID- 3111410 TI - [2 cases of localized juvenile periodontitis. Results after 2 years of treatment directed at controlling the etiological factors]. PMID- 3111412 TI - [The pediatric dentist faced with dentofacial dysmorphosis during growth: possibilities and responsibilities]. PMID- 3111413 TI - [Etiology of polycaries in a group of Tunisian children]. PMID- 3111414 TI - [Introductory report: bonded dentistry. Composites and restorations]. PMID- 3111415 TI - [Etching of the adamantine surface of the enamel. Neutreching. Scanning electron microscopy study]. PMID- 3111417 TI - [Clinical use of laminate facings or veneers in pedodontics]. PMID- 3111416 TI - [Restoration of crown fractures in the child: an esthetic solution]. PMID- 3111418 TI - [Restorations in the deciduous dentition]. PMID- 3111419 TI - [The preformed compound metal crown]. PMID- 3111420 TI - [Classification of type I and II cavity obturation technic with microfilled composites]. PMID- 3111421 TI - [Fracture resistance of non-vital teeth using various restoration technics]. PMID- 3111422 TI - [Pediatric occlusal therapy]. PMID- 3111423 TI - [Osteo-dental effects of the chin cap]. PMID- 3111424 TI - [Mouth breathing and facial growth]. PMID- 3111425 TI - [Effect of rickets on the craniofacial structures]. PMID- 3111426 TI - [Orthopedic treatment of limited oral opening. Various results in the child]. PMID- 3111427 TI - [The most frequent problems in pedodontic surgical treatment]. PMID- 3111428 TI - [Dentigerous cyst]. PMID- 3111429 TI - [Supernumerary dental fragments in the child]. PMID- 3111430 TI - [Orodental pathology in Algerian preschool children]. PMID- 3111431 TI - [Current status of oral health of young Algerians]. PMID- 3111432 TI - [Epidemiological study of the oral health status of school children 6-18-years old in the city of Blida (Algeria)]. PMID- 3111433 TI - [Organization and results of a community fluoride prevention program]. PMID- 3111434 TI - [Realities and perspectives in the use of laser fluoride in the prevention of dental caries]. PMID- 3111435 TI - [Prevention plans in primary health care]. PMID- 3111436 TI - [Clinical study of the retention and effectiveness in the prevention of occlusal caries through the use of pit and fissure sealants]. PMID- 3111437 TI - [Caries and breast feeding]. PMID- 3111439 TI - [Inhibition of caries and dental plaque with naringinine]. PMID- 3111438 TI - [Basic principles of child nutrition]. PMID- 3111440 TI - [Impact of nutrition on the orodental status of Algerian children]. PMID- 3111441 TI - [Temporomandibular ankylosis in the under-weight child]. PMID- 3111442 TI - [Polycaries of the deciduous dentition]. PMID- 3111443 TI - [Malnutrition and its orodental consequences]. PMID- 3111444 TI - Assessment of changing technologies in medicine. AB - Technology is the outcome of man's use of tools and reason to change the environment to his benefit. New technology creates opportunities for some and threats for others. New technology will be dramatically influenced by the political, social, economic, and ethical milieu in which it develops. An overriding concern in the near future may be cost. Cost-benefit analysis/cost effectiveness analysis can be a helpful planning tool but should not be used exclusively to plan for technological change. Knowledge of the humanities as well as a science will be essential if we are to make the decisions needed as we approach the 21st century. PMID- 3111445 TI - [Growth-promoting effects of histamine on Mycobacterium tuberculosis]. PMID- 3111447 TI - [Effect of histamine on immunoglobulin production of human B cells stimulated by Staphylococcus aureus Cowan I and interleukin 2]. PMID- 3111446 TI - Concentration-dependent respiratory response of guinea pigs to paraquat aerosol. AB - Six groups of male English smooth-haired guinea pigs were exposed to a paraquat aerosol for 4 h. Concentrations of the paraquat ion aerosols ranged from 0.83 to 2.07 mg/m3. Over 85% of the particles in the aerosol were found to be under 0.65 micron. Tidal volume and respiratory frequency of each animal were measured prior to exposure, immediately following exposure, and 18 h following exposure. These parameters were monitored during air breathing and a 10% CO2 challenge using a whole body plethysmograph fitted with a head chamber. A concentration-related decrease in tidal volume and increase in respiratory frequency were found 18 h following exposure when breathing air and the CO2 mixture. Inspection of the flow volume (V-VT) loops showed abnormal rectangular shapes 18 h following exposure, also varying with the concentration and indicative of lung restriction with a hyperventilation pattern. This study provides quantitative information on the respiratory toxicity following a paraquat inhalation exposure and qualitative description of its effect on the respiratory pattern. The measurements made may be of value in the search of antidotes for this important herbicide. PMID- 3111448 TI - Adolescent suicide. PMID- 3111449 TI - Annual directory. Arkansas State Dental Association. June 1987. PMID- 3111450 TI - [Neurofibromatosis and extensive intracranial arterial occlusive disease (moyamoya disease). Report of a case]. AB - A 33-year-old female with neurofibromatosis and intracranial vascular lesions of the Moya-Moya type is reported. Clinical and angiographic aspects of both syndromes are discussed with respect to earlier reports of this rare association, with the conclusion that it produces slow intellectual and motor deterioration in adolescents or young adults. There are no specific guidelines to therapy, and the prognosis is mixed, some patients ceasing to progress at least for a few years. PMID- 3111451 TI - [Gangliosidosis GM1--type 1. Anatomo-clinical study of a case]. AB - The observation of generalized GM1 gangliosidosis type 1 (Norman-Landing disease) is reported. The case is typical, featuring all the main clinical and biological signs of the disease. Diagnosis was established by the demonstration of a severe deficit in beta-galactosidase activity in leucocytes, by the demonstration of oligosaccharides in the urine, and by the histological examination after the fatal outcome before the age of two with severe respiratory distress. PMID- 3111453 TI - Use of tissue plasminogen activator in experimental hyphema. AB - Tissue plasminogen activator (tPA) is a fibrin-specific fibrinolytic agent that has recently been shown to be effective in accelerating the clearance of fibrin clots from the rabbit anterior chamber. We studied the effect of intracameral tPA on the clearance of experimental hyphema in the rabbit. Fifteen eyes were treated with an intracameral injection of tPA (1800 IU), 11 eyes were treated with a physiologic saline solution (PS) injection, and 16 eyes received no injection. Total hyphemas treated with tPA showed 80% clearance within 24 hours, while eyes treated with PS and untreated eyes cleared in 14 days. Measurement of corneal thickness revealed the tPA-treated eyes to have less corneal edema than eyes treated with PS and untreated eyes. There was no difference in intraocular pressure. The results indicate that tPA is effective in accelerating the clearance of experimental hyphema. PMID- 3111452 TI - [Ultrastructural study of conjunctival biopsies in metabolic diseases of the nervous system]. AB - Forty conjunctival biopsies from children suffering from metabolic diseases of the CNS were studied ultrastructurally. In 20 cases they were abnormal (8 mucopolysaccharidosis, 6 GM1 gangliosidosis, 4 infantile neuroaxonal dystrophy, 1 GM2 gangliosidosis, 1 late infantile ceroid lipofuscinosis). In the 20 remaining cases the biopsies did not show abnormalities. From these, 2 were proven as Leigh disease and Hallervorden-Spatz disease in which there is no conjunctival ultrastructural alterations; in 2 cases (one metachromatic leukodystrophy and one adrenoleukodystrophy) the results were false negative); in 4 clinically suspected cases of late infantile ceroid lipofuscinosis no alterations were observed and the results were not conclusive. In the remaining 12 cases the negatives allowed to rule out lysosomal disorders. The ultrastructural study of the conjunctival biopsy is an important tool for the diagnosis of neurological metabolic diseases of children mainly when sophisticated biochemical procedures are not available. PMID- 3111454 TI - Glycosaminoglycans and apolipoproteins B and A-I in human aortas. Chemical and immunological analysis of lesion-free aortas from children and adults. AB - To study changes in the contents of plasma lipoproteins in human arteries with age and the relationship of lipoproteins with other arterial constituents, we analyzed the contents of apolipoproteins B (apo B) and A-I (apo A-I), free and esterified cholesterol, and glycosaminoglycans (GAG) in lesion-free aortic intimas of 30 children and adults. The content of apo B increased significantly with age, whereas that of apo A-I remained relatively constant. Apo B and apo A-I had significant positive correlations with the content of chondroitin sulphates A + C (CS A + C), which comprised 35% to 47% of the aortic GAG. The correlations remained significant after correction for the effect of age. Aortic apo B, but not apo A-I, also showed significant positive correlations with the contents of intimal free and esterified cholesterol. The results indicate that: considerable amounts of apo B and apo A-I can be found in lesion-free aortic intimas; there is an age-related rise in the content of apo B and a fall in the ratio of apo A-I to apo B, which are unfavorable developments in the light of current views on atherogenesis; the contents of the apolipoproteins are proportional to that of CS A + C, which might have a role in the retention of lipoproteins in the arteries. PMID- 3111455 TI - Inheritance of high density lipoprotein and lipoprotein lipase and hepatic lipase activity. AB - The role of genetic and environmental factors in the regulation of plasma high density lipoprotein (HDL) was estimated in 17 monozygotic (MZ) and 18 dizygotic (DZ) male twins randomly selected from the Finnish Twin Cohort Study. In addition to HDL cholesterol, we determined the HDL subfractions, HDL2 and HDL3, and the major HDL apoproteins (apo) A-I and A-II. The activities of lipoprotein lipase (LPL) and hepatic lipase (HL) were also assayed from postheparin plasma to get information on their possible contribution to the heritability of HDL. Evidence for the genetic component in the regulation of plasma HDL received support from the heritability estimate of 0.34. The different heritability estimates of HDL2 and HDL3 (h2 of 0.56 and less than 0, respectively) support the idea that the HDL subfraction distribution might be important in the genetic regulation of plasma HDL level. This also received support from the heritability of apo A-I (h2 = 0.66), mainly varying in HDL2, and the lack of it in apo A-II, found mainly in HDL3. These conclusions were strengthened by standardizing the data with relative ponderosity. Postheparin plasma HL activity had a high pairwise correlation coefficient in the MZ twins (r = 0.80, p less than 0.001), whereas LPL displayed no within-pair correlation. Neither of the lipolytic enzymes, LPL or HL, showed any correlation in the DZ twins. Therefore, it is suggested that part of the genetic regulation of the HDL and its subfraction distribution might be mediated through the activity of HL. PMID- 3111456 TI - Apolipoprotein A-IMilano. Correlation between high density lipoprotein subclass distribution and triglyceridemia. AB - Carriers of the apolipoprotein A-IMilano (apo A-IM) variant represent a selected group of subjects showing low levels of high density lipoprotein (HDL), variable hypertriglyceridemia, and low prevalence of atherosclerotic vascular disease. The distribution of HDL subfractions and the correlation with abnormalities in triglyceride transport were determined in these subjects. Sera from 24 apo A-IM carriers (A-IM+ and from age- and sex-matched normolipidemic controls (A-IM-) were analyzed by rate zonal ultracentrifugation. The A-IM+ subjects showed a marked decrease of HDL3 mass with reduced flotation rates and major compositional alterations; the HDL2 were nearly absent. The HDL subclasses from 10 A-IM+ subjects were resolved according to particle size by gradient gel electrophoresis (GGE). The HDL patterns detected in the carriers were unique in exhibiting a distinct peak in the (HDL3b)gge interval, undetectable in the controls. Three patterns reflecting the relative contributions of smaller (HDL3b)gge and larger (HDL3a)gge particles could be distinguished in the carriers, and these were clearly related to different triglyceride and HDL cholesterol levels in plasma. These findings in a highly selected group of subjects with generally low HDL levels and quite variable triglyceridemia confirmed the existence of relationships between alterations in triglyceride transport and abnormalities in the HDL subclass distribution, possibly reflecting the variable atherosclerotic risk in hypertriglyceridemic subjects. PMID- 3111457 TI - The identity, distribution and epizootiological significance of brucella isolates in Australia, 1981 to 1985. AB - Results listing the identification of brucella isolates received by the National Brucellosis Reference Centre, National Biological Standards Laboratory, Canberra from 1981 to 1985 are presented. The distribution of brucella species and biotypes is shown on a host and state basis. Cultures isolated in Australia were identified as Brucella abortus biotypes 1, 2 and 4, and Strain 19; B. suis biotype 1, and B. ovis. B. melitensis biotype 3 was recovered from man infected in the Mediterranean area. B. abortus biotype 1 was the most frequent isolate. Atypical cultures isolated from cattle included B. suis biotype 1, and erythritol utilising mutants of Strain 19. The epizootiological implications of these findings are discussed in relation to their impact on the national campaign to eradicate bovine brucellosis. PMID- 3111458 TI - [Dental and oral hygiene: possibilities for the use of fluoride]. PMID- 3111459 TI - Influence of light intensity on rare-male advantage in Drosophila melanogaster. PMID- 3111460 TI - The partial amino acid sequence of bovine cartilage proteoglycan, deduced from a cDNA clone, contains numerous Ser-Gly sequences arranged in homologous repeats. AB - We have determined the sequence of a partial cDNA clone encoding the C-terminal region of bovine cartilage aggregating proteoglycan core protein. The deduced amino acid sequence contains a cysteine-rich region which is homologous with chicken hepatic lectin. This lectin-homologous region has previously been identified in rat and chicken cartilage proteoglycan. The bovine sequence presented here is highly homologous with the rat and chicken amino acid sequences in this apparently globular region. A region containing clusters of Ser-Gly sequences is located N-terminal to the lectin homology domain. These Ser-Gly-rich segments are arranged in tandemly repeated, approx. 100-residue-long, homology domains. Each homology domain consists of an approx. 75-residue-long Ser-Gly-rich region separated by an approx. 25-residue-long segment lacking Ser-Gly dipeptides. These dipeptides are arranged in 10-residue-long segments in the 100 residue-long homology domains. The shorter homologous segments are tandemly repeated some six times in each 100-residue-long homology domain. Serine residues in these repeats are potential attachment sites for chondroitin sulphate chains. PMID- 3111461 TI - Subsecond and second changes in inositol polyphosphates in GH4C1 cells induced by thyrotropin-releasing hormone. AB - It has been demonstrated previously that thyrotropin-releasing hormone (TRH) induces changes in inositol polyphosphates in the GH3 and GH4C1 strains of rat pituitary cells within 2.5-5.0 s. TRH also causes a rapid rise in cytosolic free calcium concentration ([Ca2+]i) in these cells which is due largely to redistribution of cellular calcium stores. Therefore, it has been concluded that TRH acts to release sequestered calcium in these cells via enhanced generation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. If this conclusion were correct, TRH enhanced accumulation of Ins(1,4,5)P3 should occur at least as rapidly as the increase in [Ca2+]i. We have shown previously that the rise in [Ca2+]i induced by TRH occurs within about 400 ms; thus, it was important to investigate the subsecond time-course of changes in inositol phosphates caused by TRH. Using a rapid mixing device, we have measured changes in inositol polyphosphates on a subsecond time scale in GH4C1 cells prelabelled with myo-[2-3H]inositol. Although TRH did alter inositol polyphosphate metabolism within 500 ms, the changes observed did not reveal a statistically significant increase in Ins(1,4,5)P3 within time intervals of less than 1000 ms. Thus, we have been unable to demonstrate that a TRH-induced rise in Ins(1,4,5)P3 precedes or occurs concomitantly with the rise in [Ca2+]i in GH4C1 cells. Although these results do not disprove the current view that Ins(1,4,5)P3 mediates the action of TRH on intracellular calcium redistribution, we conclude that caution should be exercised in this, and possibly other cell systems, in accepting the dogma that all of the rapid, agonist-induced redistributions of intracellular calcium are mediated by Ins(1,4,5)P3. PMID- 3111463 TI - L-lysinethiol: a subnanomolar inhibitor of aminopeptidase B. AB - L-Lysinethiol was found to be an extremely potent inhibitor of aminopeptidase B (AP-B) with a Ki = 9.1 X 10(-10) M. L-leucinethiol was also a potent inhibitor of AP-B (kj = 1.3 X 10(-7) M), while the D-isomer was much less effective (Ki = 9.8 X 10(-5) M). A thiol-zinc interaction at the active site is postulated for AP-B. PMID- 3111462 TI - Quantitative tissue isolation from Drosophila freeze-dried in acetone. AB - Freeze-drying procedures were developed to enable collection of tissues from Drosophila flies. The flies were frozen in acetone at -86 or -94 degrees C, and dehydrated therein. After drying, many tissues could be easily taken in entirety and free of neighbouring tissues without action of degradative enzymes. Seven polypeptide species specific to retina, and nine specific to cornea, were identified on two-dimensional electrophoretograms. Phospholipids of the dried tissues could be studied by t.l.c., and phosphatidic acid of the fly head was found to occur predominantly in the retina. Activity of three enzymes in the dried tissues could be assayed. The results of protein, phospholipid and enzyme analyses were corroborated by analyses by 'genetic dissection' using an eyeless mutant line. PMID- 3111464 TI - Stimulated production and natural occurrence of 1,2 diarachidonoylglycerophosphocholine in human neutrophils. AB - Incorporation of arachidonic acid into phospholipid molecular species of the human neutrophil was found to be dependent, to a large extent, upon the concentration of arachidonate used during the in vitro incubations. When high concentrations of [3H] arachidonate were employed, only two glycerolipids incorporated label. One glycerolipid was a unique glycerophospholipid characterized by HPLC retention time and fast atom bombardment mass spectrometry as 1,2-diarachidonoyl-sn-glycero-3-phosphocholine. The second and most highly labeled glycerolipid was found to be arachidonoyl triacylglycerol species. Human neutrophils isolated from normal individuals and not previously exposed to arachidonic acid in vitro were found to contain a small but measurable amount of diarachidonoyl-GPC. The dose-dependent increase of diarachidonoyl-GPC and arachidonoyl-labeled triacylglycerol when cells were exposed to increasing concentrations of arachidonic acid implied that these lipid molecular species have the capacity to expand their pools, perhaps in manner regulating levels of endogenous arachidonic acid for further metabolism. These observations point to the importance of the concentration of arachidonic acid employed during in vitro labeling studies. PMID- 3111465 TI - Effect of cross linkers on the bacteriorhodopsin photocycle. AB - A general behavior of bacteriorhodopsin in purple membranes from Halobacterium halobium has been observed upon modification resulting in cross-linking of carboxyl and lysine groups. The rise of the M-intermediate contained two components with approximately 50-50% intensity; its decay showed three components with approximately 25-50-25% intensity respectively in a pH range of 5-9. The significance of these remarkably similar data with respect to the proton translocation mechanism in bacteriorhodopsin is that chemical modification allows us to conclude that disturbing parts of the hypothetical "proton conducting chain" does not inhibit proton translocation. PMID- 3111466 TI - The lack of PDGE-stimulated PGE2 release from ras-transformed NIH-3T3 cells results from reduced phospholipase C but not phospholipase A2 activity. AB - Our previous work demonstrated that NIH-3T3 cells expressing high levels of the mutated cellular ras oncogene (EJ-ras gene) exhibited reduced hormone-sensitive adenylate cyclase and platelet-derived growth factor-stimulated (PDGF) phospholipase A2/C activities. We now report that although the ras-transformed cells display markedly reduced phospholipase C activity, as measured by the levels of inositol 1,4,5-trisphosphate synthesized after PDGF-stimulation, normal levels of phospholipase A2 activity can be uncovered; thus, similar levels of prostaglandin E2 were synthesized in EJ-ras transformed and control cells after stimulation with phorbol myristate acetate (PMA) and/or the calcium ionophore A 23187, agents which stimulate protein kinase C and intracellular Ca2+ levels, respectively. These data suggest that the EJ-ras gene product uncouples the PDGF receptor from the phospholipase C, resulting in reduced PDGF-stimulated Ca2+ mobilization, protein kinase C stimulation and an apparent decrease in Ca2+ dependent phospholipase A2. PMID- 3111467 TI - Mitogenic activity and inositide metabolism in thrombin-stimulated pig aorta endothelial cells. AB - The mitogenic activity of thrombin in endothelial cells is not well understood. The inositide metabolism is an ubiquitous transducing mechanism that seems to be involved in the control of cell growth. Thrombin is a potent stimulant of the release of inositol phosphates in platelets. The data presented here suggest that thrombin is able to induce competence in pig aorta endothelial cells to proliferate in response to insulin. Also thrombin is a potent stimulant of the inositide metabolism what suggests that the activation of this pathway might be at least one of the mechanisms through which thrombin induces competence in this cells. PMID- 3111469 TI - Induction of epidermal NAD(P)H:quinone reductase by chemical carcinogens: a possible mechanism for the detoxification. AB - NAD(P)H:quinone reductase, which plays an important role in the detoxification of carcinogenic metabolites as well as oxidative cellular damage, was found to be present in epidermal cytosol where its specific activity far exceeds (140-160%) the corresponding hepatic value. The effect of topical application of crude coal tar, 3-methylcholanthrene and polychlorinated biphenyl Aroclor 1254, on epidermal and hepatic cytosolic NAD(P)H:quinone reductase activities was investigated in neonatal rats, Sencar and athymic nude mice. A single topical application of each agent resulted in significant increases in epidermal (185%-389%) and hepatic (150 255%) enzyme activities. This inducible enzyme may play an important role in the detoxification of reactive quinone species during the course of malignant neoplasia and against oxidative cellular damage in skin. PMID- 3111468 TI - The formation and stability of the hypusine containing protein in Chinese hamster ovary cells. AB - Hypusine-containing protein identified as eukaryote initiation-translation factor 4D was labeled with [14C]spermidine in logarithmically growing Chinese hamster ovary cells. Radioautography of the cellular proteins separated by polyacrylamide gel electrophoresis showed the label in a single protein of 18000 Mr. Time course analysis showed that this protein remained undegraded for up to 72 hours after its synthesis. Radioactivity present in the amino acid hypusine, isolated after acid hydrolysis, remained constant during the same period of time. These results indicate that the hypusine-containing protein has a long half-life. PMID- 3111470 TI - Alteration by v-Ki-ras in NaF, cholera toxin and forskolin-induced adenylate cyclase activation in NIH/3T3 fibroblast cells. AB - It has been suggested that ras proteins are involved in the transmembrane signaling mechanism and they share structural features with GTP-binding proteins. To identify the role of ras oncogene and it's products in the coupling mechanisms of GTP-binding proteins to adenylate cyclase, we examined effect of NaF, cholera toxin and forskolin in normal and v-Ki-ras transformed NIH/3T3 fibroblast cells. In transformants, adenylate cyclase activity was markedly enhanced by NaF and cholera toxin, in contrast to normal cells. It is suggested that ras oncogene proteins plays enhancing role in coupling of GTP-binding proteins to adenylate cyclase. PMID- 3111472 TI - Some properties of tissue-type plasminogen activator reconstituted onto phospholipid and/or glycolipid vesicles. AB - Porcine heart tissue-type plasminogen activator (t-PA) was reconstituted onto large multilamellar liposomes with various lipid compositions and the kinetics of plasminogen activation by free or the reconstituted t-PA were studied. Negatively charged lipids, sulfatide and phosphatidylserine (PS), lowered the Km values of t PA for plasminogen activation (sulfatide, 20-fold; PS, 6-fold), whereas neutral lipid phosphatidylcholine raised the Km. On the other hand, these lipid environments did not affect the amidase parameters and fibrin-binding potency of t-PA. The present results suggest that t-PA could function as a cell-associated form and its plasminogen activation may be regulated by the net charge of the head group of membrane lipids. PMID- 3111471 TI - Modulation of Bacillus subtilis alpha-amylase promoter activity by the presence of a palindromic sequence in front of the gene. AB - Upstream of the promoter of the Bacillus subtilis alpha-amylase gene (amyE) derived from an alpha-amylase hyper-producing strain, there is an inverted repeat sequence (palindromic sequence), which has a free energy of 21.2 kcal/mol due to the formation of stable stem-loop structure. The role of the palindromic sequence for the expression of amyE was studied using a plasmid encoding the amyE'-'bla (E. coli beta-lactamase) fused gene in an alpha-amylase-deficient B. subtilis mutant as the host. By the presence of the palindromic sequence, the transcription activity of the amyE promoter was enhanced approximately 6 fold by starch (3%) in the medium and was less repressed by glucose. PMID- 3111473 TI - Analogs of 9-deazaadenosine: potent inhibitors of methylthioadenosine phosphorylase. PMID- 3111474 TI - Uptake of persistent environmental chemicals by cultured human cells. AB - Uptake of the persistent environmental chemicals 2,2',4,4',5,5' hexachlorobiphenyl and 1,1,1-trichloro-2,2-di-(4-chlorophenyl)ethane (the insecticide DDT) by Chang liver cells, an established human cell line, has been investigated. Monolayer cells were incubated with culture medium to which the lipophilic model compounds had been added. The time course of uptake of either compound was biphasic, reaching equilibrium after about 5 hr of incubation. The ratio of DDT:hexachlorobiphenyl uptake was dependent on the presence of serum proteins. Increasing concentrations of serum proteins in the culture medium progressively inhibited uptake. Efflux from the cells was not entirely reversible: 10-20% of the chemicals were not released. Uptake was a linear function of the external concentration of the compounds. Absorptive binding to the outer cell plasma membrane could be determined by removing bound chemicals with fetal calf serum ("back exchange"). With this method, temperature-dependent translocation through the cell plasma membrane could directly be demonstrated. The effect of low temperature as well as the influence of metabolic inhibitors point out the contribution of energy-driven uptake pathways. Demonstration of LDL receptor-like binding protein on Chang liver cells facilitated estimation of the role of receptor-mediated uptake. This route of uptake proved to be of minor importance only, as was transport of the protein-bound chemicals via fluid pinocytosis. The results demonstrate that cellular endocytosis of plasma membrane bound chemicals constitutes a major uptake pathway for lipophilic chemicals. PMID- 3111475 TI - Inactivation of bee venom phospholipase A2 by manoalide. A model based on the reactivity of manoalide with amino acids and peptide sequences. AB - The marine natural product manoalide (MLD), a potent irreversible inhibitor of bee venom phospholipase A2 (PLA2), was shown to produce a chromophore (lambda max = 437 nm) during incubation with the enzyme. MLD also developed an identical chromophore when incubated with free lysine (Lys), cysteine (Cys) or tryptophan (Trp) but not with their N-alpha-amino-blocked analogs. These results suggest that the chromophore product was dependent on the presence of two nucleophilic groups which react by an ordered mechanism rather than by simple random collision. Lys polymers prevented MLD from inhibiting PLA2, whereas monomeric Lys did not. The optimal active polymer of Lys appeared to be a tetralysine (L4) peptide, and a degree of selectivity was obtained when the Lys residues were in a 1,4-Lys arrangement. The rate of chromophore development with PLA2 and the rate of inactivation of PLA2 by MLD appear to be independent processes. Based on these data, it is possible that the irreversible inactivation of PLA2 may involve an ordered reaction with a peptide sequence in PLA2 containing a 1,4-Lys arrangement. PMID- 3111476 TI - Failure of inhibition of lipid peroxidation by vitamin E to protect against gentamicin nephrotoxicity in the rat. AB - We tested the hypothesis that accelerated lipid peroxidation, possibly at the level of the lysosome, is linked causally to the pathogenesis of aminoglycoside nephrotoxicity by investigating whether administration of vitamin E would inhibit lipid peroxidation and prevent or ameliorate gentamicin-induced proximal tubular cell injury. Five groups of rats were injected with either saline, vitamin E (600 mg/kg per day) for 6 days, gentamicin (100 mg/kg per day) for 6 days, vitamin E for 6 days plus gentamicin for 6 days or vitamin E for 12 days and gentamicin for the last 6 days. Gentamicin alone induced a 16% increase in renal cortical phospholipids; vitamin E had no significant effect on this change. Gentamicin alone caused accelerated lipid peroxidation evident by a doubling of renal cortical malondialdehyde to 1.23 nmol/mg protein, and a sharp decline of esterified polyunsaturated fatty acids, especially arachidonic acid which fell 43%. These changes were accompanied by depressions of superoxide dismutase, catalase, and total glutathione and a shift from reduced to oxidized glutathione. Concurrent treatment of rats with vitamin E plus gentamicin for 6 days had no significant effect on the gentamicin-induced alterations of malondialdehyde, superoxide dismutase, catalase or the glutathione cascade; however, the shift from polyunsaturated to saturated fatty acids was largely reversed. In rats pretreated with vitamin E for 6 days, gentamicin failed to raise renal cortical malondialdehyde above that of saline-treated rats. The changes in esterified fatty acids were prevented almost entirely, and there were no significant alterations from control of the glutathione cascade. The depressions of superoxide dismutase and of catalase, however, were not reversed. Vitamin E did not affect the amount of gentamicin accumulated in renal cortex nor did it prevent the gentamicin-induced rise of serum creatinine. Examination of renal cortex by light and electron microscopy revealed that vitamin E did not prevent or even reduce the severity of gentamicin-induced proximal tubular cell lesions and necrosis. These results confirm those we obtained in a previous study with the antioxidant diphenyl-phenylenediamine. The observation that inhibition of lipid peroxidation by two distinct antioxidants failed to prevent proximal tubular cell injury and renal dysfunction associated with gentamicin administration leads us to conclude that lipid peroxidation is a consequence and not a cause of gentamicin-induced nephrotoxicity. PMID- 3111477 TI - alpha-Difluoromethylornithine effects on nitrosourea-induced cytotoxicity and crosslinking in a methylation excision repair positive (MER+) human cell line. AB - We investigated the cytotoxic effects of nitrosoureas with and without a 42-hr preincubation with the ornithine decarboxylase (EC 4.1.1.17) inhibitor alpha difluoromethylornithine (DFMO, 1 mM) in a MER+ (methylation excision repair positive) human cell line. DFMO combined with a chloroethyl nitrosourea [1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-chloroethyl)-1-nitrosourea (CNU)] yielded increased toxicity with D37 ratios of 1.9 and 3.3 respectively. There was no enhanced toxicity with the monofunctional nitrosourea 1-ethyl-1-nitrosourea (ENU). BCNU or CNU did not induce DNA-DNA interstrand crosslinks in cells with or without a DFMO pretreatment. DNA single-strand breakage was not increased by addition of DFMO. BCNU-induced DNA-protein crosslinking was decreased in cells pretreated with DFMO. These findings are similar to those in MER- cells in that the chloroethyl carbonium alkylating species is required for the enhanced cytotoxicity seen with DFMO. The ability to form DNA interstrand crosslinks, however, does not appear to be necessary for this toxicity enhancement. PMID- 3111478 TI - Catecholamine-metabolizing enzyme activity in the nigrostriatal system. PMID- 3111479 TI - Genetic variation in cytochrome P-450-dependent demethylation in Drosophila melanogaster. AB - The genetic variation in the basal capacity to N-demethylate aminopyrine, d benzphetamine and ethylmorphine was studied in microsomes from adult Drosophila of 9 different strains. Ethylmorphine and d-benzphetamine N-demethylase activity varied about fourfold between the strains, with the highest capacity for both reactions in the Aflatoxin B1-sensitive Florida 9 and the lowest in the insecticide-resistant Hikone R. The two activities were closely correlated with each other but not with aminopyrine demethylation or any previously studied cytochrome P-450-dependent reaction, indicating a common determination by a separate cytochrome P-450 form(s). Aminopyrine N-demethylase activity was more than fourfold higher in the DDT-resistant Oregon R than in Berlin K. A genetic analysis of aminopyrine N-demethylation revealed that the high activity in the Oregon R(R) strain was inherited as an apparently semidominant second chromosome trait. The similar mode of inheritance as well as the close correlation between aminopyrine demethylase and the previously analysed biphenyl 4-hydroxylase activity suggests that these activities are under the same genetic control. PMID- 3111480 TI - Irreversible binding and metabolism of propranolol by human liver microsomes- relationship to polymorphic oxidation. AB - Studies were performed to investigate the irreversible binding and oxidative metabolism of propranolol in human liver microsomes and the relationship of binding and metabolism to the polymorphic oxidation of debrisoquine. Incubation of microsomes with 14C-labelled propranolol in the presence of a NADPH-generating system gave rise to irreversible binding which increased linearly with time and became saturated at high substrate concentrations. The extent of binding was decreased by the exclusion of cofactors, boiling, anaerobic conditions, and the addition of reduced glutathione and SKF-525A. Trichloropropene oxide had a negligible effect on cofactor-dependent binding. However, debrisoquine, antipyrine and phenacetin decreased binding to a considerable extent. The latter compound abolished cofactor-dependent binding completely at the concentration used (1 mM). Electrophoresis of microsomes which had been incubated with tritiated propranolol revealed that binding was probably occurring to a large number of proteins particularly in the 40,000-90,000 molecular weight range. Glutathione, debrisoquine and antipyrine did not inhibit the 4'-hydroxylation and N-deisopropylation of propranolol. In contrast, phenacetin exerted a very potent inhibitory action on both routes of metabolism. It is concluded that a product or products of propranolol oxidation bind irreversibly but non-selectively to human liver microsomal protein, the enzyme system responsible for the activation of propranolol appears to be related more closely to the cytochrome P-450 system which metabolizes phenacetin than to that metabolising debrisoquine, and radiolabelled propranolol is not a sufficiently specific probe for studying these cytochrome P-450 systems. PMID- 3111481 TI - Human adult hepatocytes in primary monolayer culture. Maintenance of mixed function oxidase and conjugation pathways of drug metabolism. AB - The stabilities of several drug oxidation and conjugation pathways in human adult hepatocytes have been investigated during 72 hr culture. Cytochrome P-450 dependent mixed function oxidase was measured by the O-dealkylations of ethoxyresorufin (EROD), pentoxyresorufin (PROD) and benzyloxyresorufin (BROD), which are probes for different isozymes of cytochrome P-450 in the rat. EROD declined to 64% of initial fresh cell values after 72 hr in culture, whereas PROD increased to 162% and BROD remained relatively constant. Addition of phenobarbitone to the culture medium selectively increased PROD to a greater extent than EROD and did not affect BROD. NADPH-cytochrome c reductase and NADH cytochrome b5 reductase were markedly labile during culture, declining to 32% and 22% of fresh cell values respectively. Epoxide hydrolase (EH) showed a large transient increase (2-5-fold) in enzyme activity 24 hr after culture, declining to fresh cell values by 48 hr. UDP-glucuronyltransferase (GT) activity towards phenolphthalein and 1-naphthol also increased (2-3-fold) during the 72 hr of culture, the greater and more rapid increase being observed with phenolphthalein glucuronidation. Sulphotransferase activity declined rapidly within 24 hr of culture, whereas reduced glutathione (GSH) levels and GSH conjugation were maintained at fresh cell values for 72 hr. PMID- 3111482 TI - Carrageenan-stimulated release of arachidonic acid and of lactate dehydrogenase from rat pleural cells. AB - Cells isolated from the rat pleural cavity consist mainly of macrophages, mast cells, eosinophils, and lymphocytes. Isolated pleural cells labeled with [14C]arachidonic acid released appreciable amounts (approximately 12%) of radiolabel upon exposure to pharmacological concentrations of carrageenan (1-100 micrograms/ml). The release of radiolabel was decreased by an inhibitor of phospholipase A2 (p-bromophenacyl bromide) but not by an inhibitor of arachidonate cyclooxygenase (indomethacin). The released products were arachidonic acid and, to a much lesser extent, prostaglandin E2 and leukotriene C4. The release of radiolabel was associated with release of cytosolic lactate dehydrogenase over the same range of carrageenan concentrations. Time-course studies indicated that release of radiolabel preceded that of lactate dehydrogenase. Since p-bromophenacyl bromide blocked stimulated release of radiolabel but did not prevent release of lactate dehydrogenase, it is unlikely that increase in arachidonate causes carrageenan-induced cell damage. Nevertheless, the question of whether the activation of phospholipase A2 in the pleural cells, most probably the macrophages, was sufficient to initiate the carrageenan-induced inflammatory response requires further study. Cytotoxicity which was apparent with as little as 5 micrograms/ml of carrageenan, may have been a significant consequence of carrageenan action. PMID- 3111483 TI - Induction of rat hepatic cytochromes P-450 by environmental nitropolycyclic aromatic hydrocarbons. AB - Nitrated polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that result from various incomplete combustion processes. We have examined the activity of hepatic microsomal enzymes in rats pretreated with a series of environmentally occurring nitrated PAHs including: 1- and 4-nitropyrene, 1,3-, 1,6- and 1,8-dinitropyrene, 6-nitrochrysene, 7-nitrobenz[a]anthracene, 3 nitrofluoranthene, and 1-, 3-, and 6-nitrobenzo[a]pyrene. None of the compounds increased the cytochrome P-450 content more than 2-fold. 1,8-Dinitropyrene, 6 nitrochrysene, and 1- and 3-nitrobenzo[a]pyrene significantly increased arylhydrocarbon hydroxylase activity 2- to 8-fold higher than solvent-treated controls. The induction of 7-ethoxycoumarin O-deethylase activity paralleled that found with arylhydrocarbon hydroxylase. The maximum induction of aminopyrine N demethylase was only 1.5-fold, and none of the nitrated PAHs caused significant increases in epoxide hydrase or NADPH-cytochrome c reductase. 1-Nitropyrene reductase activity was induced by each of the compounds with the exception of 6 nitrobenzo[a]pyrene. The greatest increase was caused by 1-nitrobenzo[a]pyrene followed by 1,3-dinitropyrene, 3-nitrobenzo[a]pyrene and 6-nitrochrysene. These data suggest that nitrated PAHs may potentiate the effects of subsequent exposures to various chemical carcinogens. PMID- 3111484 TI - Induction of hepatic cytochrome P-450c-dependent monooxygenase activities by dantrolene in rat. AB - The effect of dantrolene sodium, a skeletal muscle relaxant, on drug metabolizing enzymes has been investigated after treatment of rats with a dose of 200 mg/kg for five days. We observed an induction of cytochrome P-450c and epoxide hydrolase in immunoassays and activities. An enhancement of the UDP glucuronosyltransferase (GT1) activity was observed. We also reported a decrease of both liver cytochrome P-450 content and microsomal cytochrome P-450b dependent N-demethylation activities. On the other hand, the binding of dantrolene on microsomal cytochrome P-450 produced a type I difference spectrum, these data were obtained with liver microsomal cytochrome P-450c induced by 3 methylcholanthrene. PMID- 3111485 TI - Altered metabolism of [18F]-6-fluorodopa in the hooded rat following inhibition of catechol-O-methyltransferase with U-0521. AB - [18F]-6-Fluoro-L-DOPA ([18F]DOPA), a tracer for cerebral dopamine in studies utilizing positron emission tomography (PET), is rapidly metabolized by catechol O-methyltransferase (COMT) in the periphery following intravenous injection to carbidopa-pretreated humans and rats. Experiments were performed to determine the effect of pretreatment with 3',4'-dihydroxy-2-methyl-propiophenone (U-0521), a competitive inhibitor of COMT, on [18F]DOPA metabolism in the carbidopa pretreated hooded rat. U-0521 (25 mg/kg, i.p.), administered 10 min prior to the [18F]DOPA, served to increase the persistence of [18F]DOPA in plasma over a 2-hr period by decreasing the rate of formation of the peripheral metabolite 3-O methyl-6-fluorotyrosine (Me[18F]DOPA). This compound passes readily into brain and was the sole [18F]DOPA metabolite observed in cortex and cerebellum. U-0521 produced a short-lasting decrease in Me[18F]DOPA levels in these two tissues. In striatum, decreases in Me[18F]DOPA were found to last at least 90 min. Associated with the elevated availability of [18F]DOPA in plasma produced by U-0521 were 50% increases in striatal [18F]dopamine ([18F]DA) levels and 40% increases in the levels of [18F]dihydroxyphenylacetic acid ([18F]DOPAC) at times between 30 and 90 min following [18F]DOPA injection. Increased decarboxylation of [18F]DOPA in the striatum of U-0521-treated rats resulted in heightened radiocontrast between striatum and other cerebral tissues. PMID- 3111486 TI - Hepatic cytochrome P-450 system in experimental hepatosplenic schistosomiasis. Presence of an artifact in spectrophotometric analysis. AB - Several recent reports suggesting that the liver microsomal cytochrome P-450 system is impaired in Schistosoma mansoni infections in mice prompted a detailed investigation of the hepatic cytochrome P-450 system in murine schistosomiasis. Mice were prepared with three levels of Schistosoma mansoni infection and studied 8, 12 and 14 weeks post-exposure. Histological sections of the liver confirmed prominent granuloma formation and portal fibrosis which was dose and time dependent. Cytochrome P-450 levels appeared reduced grossly in microsomes from homogenates of infected livers, but accurate quantitation was complicated by the presence of a prominent peak at 422 nm. Ethylmorphine N-demethylase activity also appeared to be reduced in all infected animals, reaching a maximum decrease at 14 weeks of 44% of control values in the most heavily infected mice. NADPH cytochrome c reductase activity and cytochrome b5 levels were similarly reduced. Utilization of techniques to separate hepatocytes from granulomatous material in infected livers eliminated the 422 nm peak and reversed several of the findings made with whole-liver derived microsomes. Cytochrome P-450 levels were reduced modestly (30%) at 8 weeks in the most heavily infected mice but returned to normal values by 14 weeks. Specific ethylmorphine N-demethylase activity of isolated hepatocytes was increased at 8 weeks with a return to normal by 14 weeks. Isolated granulomata were incriminated as one possible source of the 422 nm pigment in whole-liver derived microsomes but appeared unlikely to account fully for this finding. Thus, this investigation concluded that the cytochrome P 450 system is altered by experimental murine hepatosplenic schistosomiasis, but such alterations are subtle in nature and unlikely to contribute in major fashion to the observed changes in drug disposition. PMID- 3111487 TI - Effect of protein concentration on the binding of gold(I) to human serum albumin. AB - The binding of aurothiosulphate, gold(I), by human serum albumin has been studied by equilibrium dialysis at four different albumin concentrations, 37 degrees, pH 7.2-7.4 and ionic strength 0.15 M. The results show that the interaction of aurothiosulphate with albumin depends on albumin concentration. This observation is linked with the previous observation that the usual independent site description cannot be used to represent the clinically important low concentration data. All the observed dependences are satisfactorily accounted for by assuming that gold(I) competes with a highly bound contaminant for the high affinity (Cys(34)-SH) site. This description is supported by the experimental observation that a fraction of this site is originally blocked both in vivo and in in vitro. The present interpretation yields a high affinity binding constant 100 times larger than found previously and provides an explanation for the lack of correlation between dose and therapeutic and toxic effects in chrysotherapy. PMID- 3111488 TI - [Localization of lysine residues in the site of initiating substrate binding of E. coli RNA-polymerase]. AB - Superselective affinity labelling of E. coli RNA polymerase in a complex with the promoter-containing fragment of T7 DNA by treatment with orto-formylphenyl ester of GMP followed by addition of [alpha-33P]UTP resulted in covalent binding of the residue--pGpU (p-radioactive phosphate) with one of lysine residues of the beta subunit, Lys1048, Lys1051, Lys1057, Lys1065. The amino acid sequence of this region of the beta-subunit of E. coli RNA polymerase has a high extent of homology with that deduced for a region of tobacco chloroplast RNA polymerase on the basis of the nucleotide sequence of the chloroplast rpoB-like gene. PMID- 3111490 TI - Articular indices of joint inflammation in rheumatoid arthritis. Correlation with the acute-phase response. AB - The joints of 30 rheumatoid arthritis patients were assessed by one observer for signs of inflammation. Computer analysis was then used to calculate 70 different articular indices for each patient. Pearson correlation coefficients were calculated between serum C-reactive protein levels and the articular indices. The results show that: findings in a restricted set of examined joints were equivalent to those in a more complete set; the simultaneous presence of joint tenderness and swelling yielded higher correlation than did either variable alone; and joint "weighting" for size yielded higher correlation than did simple counts. PMID- 3111489 TI - Antinuclear antibody, lupus anticoagulant, and anticardiolipin antibody in women with idiopathic habitual abortion. A controlled, prospective study of forty-four women. AB - In a controlled, prospective study of 44 consecutive women with idiopathic habitual abortion, only 5% had symptoms of rheumatic disease. Patients did not differ from control subjects in the frequency of positive results on tests for antinuclear antibody or anti-double-stranded DNA. Levels of C3 and C4 were higher in the habitual aborters. No patients had anti-Ro. The antiphospholipid antibody results were analyzed using 2 methods: the frequency of antiphospholipid antibodies was 9% by lupus anticoagulant using the Russell viper venom time (95% confidence interval 22-2.5) and 11% by anticardiolipin antibody assay (95% confidence interval 25-3.7), which was not significantly different from that in control subjects. However, the mean levels in the aborters (although within the normal range) were significantly higher than those in control subjects for anti double-stranded DNA (P = 0.004), lupus anticoagulant (by Russell viper venom time; P = 0.05), and anticardiolipin antibody (P = 0.0007), when examined by multiple linear regression analysis corrected for age and concurrent pregnancy. Of the 3 patients with antiphospholipid antibodies and subsequent successful pregnancies, only 1 was treated with prednisone and aspirin. We conclude that, in the majority of women, subclinical lupus, anti-Ro, the lupus anticoagulant, and anticardiolipin antibodies are not associated with idiopathic habitual abortion. PMID- 3111491 TI - Artery wall derived proteoglycan-plasma lipoprotein interaction: lipoprotein binding properties of extracted proteoglycans. AB - Artery proteoglycan-lipoprotein binding characteristics were determined using intact, high molecular weight chondroitin sulfate proteoglycans (CS-PG) isolated from grossly appearing normal aortas of atherosclerosis susceptible WC-2 pigeons and plasma lipoproteins from normolipemic, randomly bred White Carneau pigeons. Optimum formation of particulate proteoglycan-lipoprotein complexes occurred in 5 mM Tris, 6 mM KCl, 4 mM CaCl2, 1 mM MgSO4, pH 7.2. The binding of CS-PG was specific for low density lipoprotein (LDL) and not high density lipoprotein (HDL). The relative importance of the intact monomeric structure of the PG was suggested in studies where glycosaminoglycan chains isolated from the PG monomer possessed less than 1% of the binding reactivity of the intact PG. The core protein prepared from the CS-PG monomer formed no measurable particulate complex. PMID- 3111492 TI - Lipoprotein interaction with artery wall derived proteoglycan: comparisons between atherosclerosis-susceptible WC-2 and resistant Show Racer pigeons. AB - The binding of intact, high molecular weight, aortic proteoglycan (PG) isolated from grossly normal appearing aortas of atherosclerosis-susceptible White Carneau pigeons (WC-2) and -resistant Show Racer pigeons (SR) to homologous and heterologous serum lipoproteins from both normolipemic and hyperlipemic pigeons was examined. In vitro binding studies were done using a mixture of purified chondroitin sulfate PG and dermatan sulfate PG monomers to simulate an in situ composition. For each animal, a binding potential or reactivity number was calculated and corresponded to the shape and slope of the PG-LDL binding curve, where higher values indicated greater reactivity. For WC-2 normal sera, mean values were 0.97 and 0.95 using WC-2 and SR PG respectively, compared to SR normal sera (equivalent total plasma cholesterol) where values were 0.80 and 0.82. Corresponding mean reactivity values for hyperlipemic sera (diluted to a cholesterol concentration of 300 mg/dl) were 0.95, 1.00, 0.73, and 0.79. The results suggest that LDL from both normolipemic and hyperlipemic atherosclerosis susceptible WC-2 pigeons is more reactive in complexing to artery wall derived PG than LDL from SR pigeons, regardless of PG source. PMID- 3111493 TI - Allophycocyanin complexes of the phycobilisome from Mastigocladus laminosus. Influence of the linker polypeptide L8.9C on the spectral properties of the phycobiliprotein subunits. AB - The following phycobiliproteins and complexes of the allophycocyanin core were isolated from phycobilisomes of the thermophilic cyanobacterium Mastigocladus laminosus: alpha AP, beta AP, (alpha AP beta AP), (alpha AP beta AP)3, (alpha AP beta AP)3L8.9C, (alpha APB alpha AP2 beta AP3)L8.9C. The six proteins and complexes were characterised spectroscopically with respect to absorption, oscillator strength, extinction coefficient, fluorescence emission, relative quantum yield, fluorescence emission polarisation and fluorescence excitation polarisation. The interpretation of the spectral data was based on the three dimensional structure model of (alpha PC beta PC)3 (Schirmer et al. (1985) J. Mol. Biol. 184, 257-277), which is related to the allophycocyanin trimer. The absorption and CD spectra of the complexes (alpha AP beta AP)3, (alpha AP beta AP)3L8.9C and (alpha APB alpha AP2 beta AP3)L8.9C could be deconvoluted into the spectra of the phycobiliprotein subunits. The assumptions made for the deconvolution could be checked by the synthesis of the spectra of (alpha APB beta AP)3. The synthesised spectra are in good agreement with the corresponding measured spectra published by other authors. Considering the deconvoluted spectra the following influences on the chromophores could be ascribed to L8.9C: L8.9C neither influences the alpha AP nor the alpha APB chromophores. L8.9C shifts the absorption maximum of the beta AP chromophore to longer wavelength than the absorption maximum of the alpha AP chromophore in trimeric complexes. L8.9C increases the oszillator strength of the beta AP chromophores to about the value of the alpha AP chromophores in trimeric complexes. L8.9C turns the beta AP chromophores from sensitizing into weak fluorescing chromophores. By means of the hydropathy plot and the predicted secondary structure, a postulated three-fold symmetry in the tertiary structure of L8.9C could be confirmed. PMID- 3111494 TI - Structure and properties of enzyme graft copolymers: effects of using dissolved agarose on horseradish peroxidase immobilization. AB - The immobilization of horseradish peroxidase (HRP) onto dissolved agarose by a photochemically initiated graft copolymerization reaction, carried out at room temperature, was studied. Enzyme immobilization parameters such as the catalyst (FeCl3) and the enzyme concentration were considered. Using hexhydro-1,3,5 triacryloyl-s-triazine (HTsT) as vinyl monomer, the agarose/HTsT ratio was the main reaction parameter controlling the copolymer characteristics. By increasing the polymer content of the sample better stability properties were obtained. For the samples with agarose/HTsT ratios of 20/40 and 40/20 (S 20-40, S 40-20) the residual activities after 240 min at 60 degrees C were respectively 47 and 18%. The residual activity in continuous working was 33% for S 40-20 (after 20 h) and 64% for S 20-40 (after 70 h). For both the synthesized copolymers no limitation to substrate diffusion was found but the flexibility of immobilized enzyme decreased with the increase of polymer content as indicated by the Km values that were 0.90 X 10(-4) mol/liter for the sample S 40-20, and 1.50 X 10(-4) mol/liter for the sample S 20-40. Other enzymes (glucose oxidase, alpha-chymotrypsin, and lipoxidase), besides HRP, were immobilized with good yields, showing the wide applicability of the proposed methodology for the preparation of a solid biocatalyst which can be conveniently stored in water suspension or as lyophilized material. PMID- 3111495 TI - beta-Glucosidases from cellulolytic fungi Aspergillus terreus, Geotrichum candidum, and Trichoderma longibrachiatum as typical glycosidases. AB - By ethanol precipitation (v/v) and chromatography on Sephadex SP, DEAE (or DEAE cellulose), and G-200 beta-glucosidases (EC 3.2.1.21) from the culture filtrates of cellulolytic fungi Aspergillus terreus, Geotrichum candidum, and Trichoderma longibrachiatum grown on the medium with cellulose containing materials were isolated. The enzymes were homogenous as shown by different techniques. The substrate specificities of the obtained enzymes were studied. beta-Glucosidases had higher affinity for p-nitrophenyl-beta-D-glucopyranoside than for cellobiose (Km 1.25, 0.34, 0.20 and 5.4, 2.0, 1.2 mM, respectively) and were able to hydrolyze both laminaribiose and gentiobiose; but they were unable to cleave cotton fiber, carboxymethylcellulose, and other glycans to reducing sugars. They showed transglycosylase activity. Ki values for arylglucosidase activity of beta glucosidases from A. terreus, G. candidum, and T. longibrachiatum in the presence of either glucose or glucono-1,5-lactone were 12.2, 6.0, 2.1 and 0.20, 0.19, 0.07 mM, respectively. The Mr's were estimated by gel filtration and by sedimentation equilibrium centrifugation to 200,000, 200,000, 350,000, respectively. The isoelectric points of beta-glucosidases were 4.8, 5.9, and 4.2, respectively. The optimum temperatures and pH's were 60, 50, and 50 degrees C and at pH 4.5, 4.5, and 4.8-5.7, respectively. These properties appear to relate beta-glucosidases obtained in the present study to typical glycosidases. PMID- 3111496 TI - Studies on the enzymatic hydrolysis of amino acid carbamates. AB - Several commercially available enzymes were tested for their ability to hydrolyze amino acid carbamates. No activity was found with pig liver esterase, the hydantoinase from Pseudomonas fluorescens DSM 84, or the urease from jack beans. A stereoselective cleavage of the carbamyl group yielding L-amino acids was observed by acylase and acetylcholinesterases from bovine and human erythrocytes. Racemic mixtures of N-(methoxycarbonyl)-DL-alanine, N-(ethoxycarbonyl)-DL alanine, and the corresponding valine carbamates are hydrolyzed to L-alanine and L-valine, respectively, by acylases leaving the D-amino acid carbamates unchanged. The lysine carbamates were not hydrolyzed by acylases. In contrast only the methoxycarbonyl amino acids were split by acetylcholinesterases, which, however, also cleave alpha, epsilon-(N-methoxycarbonyl)-DL-lysine stereoselectively at the alpha position, yielding epsilon-N-methoxycarbonyl-L lysine. The optimum pH for enzymatic activity of hog kidney acylase was 7.5 and a Km value of 8.2 mM for N-(methoxycarbonyl)-DL-alanine was determined. For the acetylcholinesterases the reaction rate reaches an optimum between pH 7.5 and 8. The Km value was 68 mM for N-(methoxycarbonyl)-DL-alanine. PMID- 3111497 TI - T-cell-dependent modulation of the polyclonal B-lymphocyte responses in normal spleen cell cultures stimulated by lipopolysaccharide. AB - The in vitro polyclonal B-cell proliferative and plaque-forming cell (PFC) responses to the T-independent (TI) mitogen lipopolysaccharide (LPS) are increased by the addition of normal syngeneic splenic T cells. Normal irradiated Lyt-2- T cells also alter the IgG subclass distribution from the typical predominance of IgG3 and IgG2b PFC to the appearance of IgG1, IgG2a and IgA PFC in T-cell-depleted spleen cell (SC) cultures. Furthermore, secondary LPS blast cultures yield increased PFC responses when co-cultured which syngeneic fresh normal T cells which, even in the absence of mitogen, induce PFC responses in such activated B cells. As LPS blasts induce normal syngeneic T cells to proliferate and significant numbers of L3T4+ blast cells are found in LPS stimulated normal spleen cell cultures, we conclude that T cells actively participate in the regulation of these responses. The significance of these findings for the regulation of TI responses in vivo by "autoreactive" T cells is considered. PMID- 3111498 TI - The role of cytoplasmic granule components in cytolytic lymphocyte-mediated cytolysis. PMID- 3111499 TI - Quaternary structure of intestinal maltase-glucoamylase in pancreatectomized rats. AB - Detergent-solubilized intestinal maltase-glucoamylase was isolated 1 week postpancreatectomy (dMpanc) and purified in the presence of detergent and protease inhibitors. Upon sodium dodecyl sulfate - polyacrylamide gel electrophoresis under nondissociating conditions, the major band had a molecular weight of 280,000, slightly smaller than similar bands from detergent (dM) and papain (pM) solubilized maltase from nonpancreatectomized rats. Upon octyl Sepharose CL-4B chromatography, 57% of the enzyme was eluted by aqueous buffer, unlike pM which was almost completely eluted or dM, 95% of which bound to the column. All fractions of dMpanic from octyl-Sepharose 4B were reduced, by boiling +/- beta-mercaptoethanol, to monomeric subunits, indicating that processing by pancreatic enzymes at the level of the brush border is not a requirement for the appearance of subunits in the rat. As well, under these dissociating conditions, the 145,000 subunit previously identified with the apolar terminus was present in all fractions of dMpanc, including the aqueous fraction, whereas pM contained only the 130,000 subunit. The presence of dMpanc in the aqueous fraction cannot be explained, therefore, by proteolytic cleavage of an apolar anchor segment from the 145,000 subunit. Pancreatic enzymes may affect the enzyme in a minor fashion, however, since aqueous solubility was enhanced and the apparent molecular weight was reduced by pancreatectomy, suggesting a more compact conformation with shielding of apolar segments. PMID- 3111500 TI - Equipment for radiation surgery using narrow 185 MeV proton beams. Dosimetry and design. AB - The purpose of the present work was to optimize and standardize irradiation conditions and dosimetry methods in order to investigate the prerequisites for the routine use of narrow high energy proton beams for cerebral radiation surgery. Particular importance was laid on the design of the arrangements for defining and controlling the path of the beam in the laboratory in view of the desirability of working with well-defined parallel beams containing a minimal contribution of scattered and secondary radiation. At the same time it was intended that this apparatus should be used to adjust the beam reproducibly onto an ideal beam path prior to each irradiation session. It was also considered desirable to be able to supervise the centering and the structure of the beam during the irradiations in view of the variations which can arise due to varying running conditions in the synchrocyclotron. The beam was collimated and led to the place where the irradiations were to be performed, 25 metres from the synchrocyclotron, with a system of focusing quadrupole magnets and bending magnets. Final collimation of the beam penetrating the object was arranged with a system of accurately aligned cylindrical and plane-parallel metal apertures. The energy of the protons in the beam was 185 +/- 0.2 MeV and the maximum total fluence was 5 X 10(10) protons/s. A method of 11C activation dosimetry was developed with which an absolute determination of the fluence and the dose in the proton beam could be made with good accuracy. These determinations were performed by irradiating small polystyrene cylinders placed along the beam axis at the isocentre. The activity induced in the cylinders by the protons was measured in a well-type crystal detector. The efficiency of the detector for the detection of annihilation photons was determined before each measurement by means of calibration with standardized activities of 22Na and 60Co. The overall uncertainty in the dose determinations using 11C activation dosimetry was +/- 8 per cent. Monitoring of the dose during irradiation was performed with an ionization chamber. Since it was most important to minimize the scattering of the protons, this chamber was designed as a 'free air chamber' with the electrodes parallel to the beam. The chamber could not be used for absolute measurements, however, since there was a contribution to the ionization in the chamber from scattered protons and secondary radiation from the walls of the collimator defining the cross section of the ionization volume.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3111501 TI - Enzyme immunoassay for diagnosis of bovine brucellosis. PMID- 3111502 TI - The lipopolysaccharides of Brucella abortus and B. melitensis. PMID- 3111503 TI - Relationship of biological activities to structures of Brucella abortus endotoxin and LPS. PMID- 3111505 TI - [Determination of biovars of Brucella melitensis by manometric character: epidemiological value and relation to serovars]. AB - As Brucella melitensis is the most frequently encountered Brucella species in human medicine, and as its subdivision into three serovars is insufficient for epidemiological studies, we sought to define a new scheme for biotyping of this species. For this purpose, we studied 94 strains for their oxidative metabolic rates on 32 substrates and their susceptibility to ten antibiotics, and 132 strains for their activities with three enzymes. A taxonomic study on the basis of the 32 oxidative metabolic rates led to the distinction of five biovars which could then be defined by means of the five most discriminating substrates. Among the ten antibiotics tested, only three showed varying patterns of susceptibility. Oxidative metabolic rates were not correlated with these patterns of susceptibility nor with the enzymatic activities. However, a relationship was found between biovar and serovar, especially with regard to the following substrates: meso-erythritol, deoxythymidine, D-galactose and DL-phenylalanine. As shown by correspondence analysis, the repartition of biovars significantly differed among French administrative regions. PMID- 3111504 TI - Deletions in the tetracycline resistance determinant reduce the thermosensitivity of a trfA(Ts) derivative of plasmid RP1 in Pseudomonas aeruginosa. AB - A derivative of the broad-host-range plasmid RP1, pME301, was temperature sensitive (Ts) at 43 degrees C for maintenance in Pseudomonas aeruginosa, P. mendocina, Klebsiella aerogenes and Escherichia coli. In E. coli, the Ts defect of pME301 could be complemented in trans by the cloned trfA gene, which is known to be essential for RP1 replication in E. coli and P. aeruginosa. Because pME301 expressed a Ts phenotype in P. mendocina and K. aerogenes, we assume that the trfA function is also vital in these organisms. When plasmid-encoded carbenicillin resistance (on transposon Tn801) was selected at non-permissive temperatures in P. aeruginosa strain PAO carrying pME301, we obtained either Tn801 insertions into the chromosome or pME301 derivatives having a deletion (or point mutation) in their tet genes, which determine resistance to tetracycline and are not transposable. From cloning experiments, we infer that the tet gene product(s) destabilize the pME301 replicon in P. aeruginosa at 40-43 degrees C. PMID- 3111506 TI - [Comparative immunological study of glyceraldehydephosphate dehydrogenase in Enterobacteriaceae: contribution of an anti-glyceraldehydephosphate dehydrogenase antiserum of Enterobacter intermedium]. AB - A comparative immunological study of glyceraldehyde-3-phosphate dehydrogenase among Enterobacteriaceae was carried out with an antiserum against Enterobacter intermedium G-3-PDH. Results of immunodiffusion experiments and microcomplement fixation studies showed E. intermedium to be a homogeneous species. The genera Enterobacter and Escherichia were found to be quite heterogeneous. PMID- 3111507 TI - 3rd Forum de Microbiology. Virulence of Listeria monocytogenes. PMID- 3111508 TI - Effects of alfentanil on the pressor and catecholamine responses to tracheal intubation. AB - The effects of alfentanil (given during induction of anaesthesia) on the haemodynamic and catecholamine responses to tracheal intubation were studied in 44 adult patients who received alfentanil 10 micrograms kg-1 or 40 micrograms kg 1, or saline placebo. Alfentanil 10 micrograms kg-1 and 40 micrograms kg-1 prevented any increase in heart rate and arterial pressure after tracheal intubation. Alfentanil 40 micrograms kg-1 produced profound hypotension and bradycardia. The use of alfentanil in both doses was associated with a decrease in plasma adrenaline concentrations after tracheal intubation. PMID- 3111510 TI - Abnormal alfentanil pharmacokinetics. PMID- 3111509 TI - Mutagenicity of the combination of a volatile anaesthetic and nitrous oxide. AB - The mutagenic potential of halothane, enflurane and isoflurane in combination with nitrous oxide was investigated using the sex-linked recessive lethal assay in the fruit fly Drosophila melanogaster. Male wild-type flies were exposed for 1 h to 1 or 2% volatile anaesthetic with various concentrations of nitrous oxide up to 75%. They were then mated with untreated females of the Basc marker strain. A brooding pattern was used to assess mutagenicity at different germ cell stages. The rate of lethal mutations was assessed in the F2 generation. Halothane produced a dose-dependent increase in the rate of lethal mutations, but the mutagenicity was independent of the presence of nitrous oxide and of the stage of germ cell formation. Neither enflurane nor isoflurane was mutagenic in the presence of nitrous oxide. PMID- 3111511 TI - Data Note--9. Measuring the social costs of addictive substances. PMID- 3111512 TI - Variations in response to non-steroidal anti-inflammatory drugs. PMID- 3111513 TI - Paracetamol interaction with oral contraceptive steroids: increased plasma concentrations of ethinyloestradiol. AB - The effect of a single dose of paracetamol (1 g) on plasma concentrations of the oral contraceptive steroids ethinyloestradiol (EE2) and levonorgestrel (LNG) has been studied in six healthy female volunteers. The area under the plasma concentration-time curve (AUC0-24) of EE2 was significantly increased following paracetamol administration by 22% (control 2221 +/- 291; following paracetamol, 2702 +/- 452 pg ml-1 h; mean +/- s.d.; P less than or equal to 0.05). The greatest effect was evident in the time period 0-3 h. There was a significant decrease in the AUC of EE2-sulphate after paracetamol (7736 +/- 3791 pg ml-1 h) compared with control (13161 +/- 4535 pg ml-1 h; P less than or equal to 0.05). Plasma concentrations of LNG were unaltered by concurrent paracetamol administration. We conclude that the administration of a single 1 g dose of paracetamol causes an increase in plasma concentrations of EE2 as a result of a reduction in the sulphation of the steroid. This interaction may be of clinical significance in women on oral contraceptive steroids who regularly take paracetamol. PMID- 3111514 TI - The paradoxical effect of cimetidine and ranitidine on glibenclamide pharmacokinetics and pharmacodynamics. AB - The potential interactions between H2-receptor antagonists, cimetidine and ranitidine, and glibenclamide were studied in 15 non-smoking male volunteers. The study consisted of six treatment phases. Treatment A (3 h oral glucose tolerance test) consisted of 75 g dextrose in 300 ml carbonated water. Treatment B consisted of one 5 mg tablet of glibenclamide in addition to a glucose tolerance test. Treatment C, cimetidine 300 mg orally four times daily for 4 days and Treatment D, ranitidine 150 mg orally twice daily for 4 days were administered in a randomized, crossover fashion. On day 3 of Treatments C and D, subjects received an oral glucose tolerance test. On day 4 of Treatments C and D, subjects received 5 mg of glibenclamide in addition to cimetidine (Treatment E) or ranitidine (Treatment F) and an oral glucose tolerance test. Compared with the control treatment, cimetidine increased the glibenclamide AUC (973 vs 710 ng ml-1 h), but during ranitidine dosing glibenclamide AUC (726 ng ml-1 h) was not significantly different from the control. Apparent oral glibenclamide clearance decreased from 8.25 l h-1 under the control treatment to 6.0 l h-1 following cimetidine but was unchanged during ranitidine (7.97 l h-1). Plasma glucose concentrations were unexpectedly higher when glibenclamide was administered with cimetidine or ranitidine (glucose AUC 237 mg dl-1 h, 228 mg dl-1 h) when compared with glibenclamide administered alone (195 mg dl-1 h, P less than 0.0001). Plasma insulin concentrations were significantly elevated when H2-receptor antagonists and glibenclamide were administered concurrently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111516 TI - Tissue distribution and hepatic ultrastructural effects of aflatoxin B1 in Japanese quail. AB - Fertile, Japanese quail eggs were injected with graded levels of aflatoxin B1 (AFB1) dissolved in ethanol. Hatchability varied inversely with the quantity of AFB1 administered. The generated quail were utilized in studies of AFB1 distribution and its effects upon hepatic ultrastructure. Putative AFB1 was detected within the livers of two quail 6 h after dosing, although the AFB1 distribution was inconsistent between the individuals. Electron microscopy revealed that liver parenchymal cells from AFB1-treated exhibited mitochondrial pleomorphism 6 h after dosing, a rare observation in control tissue. PMID- 3111515 TI - Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy. AB - A small pre-treatment 'priming' dose of cyclophosphamide will reduce gut damage due to high dose i.v. melphalan in mice and sheep but efforts to demonstrate this effect in man have been hampered by difficulty in the measurement of gut damage. We have evaluated the 51CR EDTA absorption test, a new method for measuring intestinal permeability, as a means of assessing damage due to high dose melphalan. The test was reliable, with a narrow normal range, easy to use and well tolerated. It detected an increase in intestinal permeability after high dose melphalan with a maximum occurring between 9 and 15 days after treatment and subsequently returning to normal. It was shown in 19 patients that a pre treatment dose of cyclophosphamide was capable of significantly reducing the abnormalities in intestinal permeability which resulted from high dose melphalan. PMID- 3111517 TI - [Causes of lamb losses with special reference to listeriosis on a large-scale farm]. AB - Epizootiological studies on lamb losses on a large scale farm (4.5 thousand mothers) were carried out. The results of the studies denied the direct effect of maize silage on the genesis of enzootia of listeriosis. The earlier reports were confirmed, i.e. that the direct cause of enzootia of listeriosis is the weakening of an animal organism due to other microbiological, zoohigienical, nutritional factors (e.g. not proper content of mineral compounds). Maize silage has a destructive effect on the health of lambs as well as other fodders with unsuitable biochemical composition. The results of the studies were prepared in Basic language using Hellwig's method "Determination of the maximum capacity of data carrier", to enable the automation of statistical data. Verification of the above mentioned method was done on the basis of the results of the studies performed on a sheep farm. Essential influence of the content of magnesium and iron as well as statistically known interdependencies between the indices studied were revealed and confirmed. "Listing" of the programme; data and result printout, to be used widely, was enclosed. PMID- 3111518 TI - [Diagnostic value of the rose bengal plate test in the diagnosis of bovine brucellosis]. AB - The value of rose bengal plate test (RBPT) in diagnosing brucellosis in cattle was determined by statistical comparison of its results with the results of the tests used in Poland, i.e. SAT, CFT, AGT and MET. RBPT was made in 2 variants. In routine, highly specific test, equal parts of antigen and serum--0.03 cm3, were used whereas in the experimental one the sensitivity was increased using half the amount of antigen--0.015 cm3 (RBPT0.015). Two batches of cattle serum were examined. In group I 249 cattle serums from the herds infected with brucellosis were examined. In group 2 there were 1269 cattle serums from the herds free of brucellosis, positive in SAT but negative in CFT. The reactions in SAT were considered as not specific if the reaction in the additional examination in CFT, AGT and MET was negative. On the basis of the results in group I, mainly the sensitivity of RBPT was determined compared with the total evaluation of the results of SAT/CFT. In RBPT0.015 the consistency of the results was 99.4% but in RBPT0.03 only 87.9%. Detectability of reactions, i.e. the percentage of positive results in infected herds was calculated. The results were as follows: AGT- 89.6%, RBPT0.015--74.3%, SAT/CFT--66.3%, CFT--65.9%, RBPT0.03--59.8%, SAT--55.4%. In the group 2 mainly specificity of RBPT in relation to CFT, AGT and MET was determined. In RBPT0.03 it achieved 97.1% whereas in RBPT0.015--83.1%. The application of RBPT0.03 in the group 2 eliminated 95.8% of the not specific reactions in SAT and that of RBPT0.015--77.9%, respectively. The author suggests to use RBPT0.03 as a screening method instead of SAT and CFT to diagnose cattle brucellosis in the areas free from the disease. On the other hand, RBPT0.015, as more sensitive test is suggested to be used in the herds suspected of brucellosis to identify quickly infected animals. PMID- 3111519 TI - [Polish standard for anti-Brucella abortus serum for agglutination as the basis for the standardization of the antigen for the rose bengal plate test]. AB - The aim of the study was to test out the usability of Polish Standard of anti Brucella abortus serum in agglutination for standardization and control of antigen commercial manufacturing. Polish Standard of anti-Brucella abortus serum in agglutination tube test (PSaBaS-SAT) was separated on Sefadeks G-200 gel to determine the content of anti-Brucella antibodies of IgM class, characteristic of the first stage of infection, and IgG antibodies typical for chronic disease. Serological examinations of the fractions obtained, revealed significant domination of specific IgG antibodies over IgM. Visible activity of IgG in RBPT (Rose Bengal Plate Test) and in other serological test used in Poland to recognize brucellosis, was observed. It enables us to use PSaBaS-SAT in the determination of agglutinability of acid antigen as the antibodies of this class are commonly recognized to be a specific indicator of active brucellosis on the contrary to IgM which may be of non specific character. It is suggested that additional testing of agglutinability of acidic antigen, compared to IgM antibodies is not necessary and increases the cost of studies. Moreover, the examination of animals twice a year, using RBPT gives slight probability to find animals in their first stage of infection (high level of IgM in serum) as the only ones in the population studied. PMID- 3111520 TI - Prozone of the complement fixation test (CFT) in the diagnosis of bovine brucellosis. AB - Sera of cows with brucellosis and those originating from heifers vaccinated with S19 strain, were investigated. A great negative relationship was observed between the frequency of CFT prozone occurrence and the living conditions of the animals; the individual properties of the animals were less significant, and the experimental error still lesser. No relationship was found between the kind of animal stimulation (field infection or S19 vaccination), the stadium and severity of the disease, the CFT titre level, and the animal age. The herd prozone frequency showed a normal distribution in the coordinate system. PMID- 3111521 TI - Studies on the usefulness of the antiglobulin test (AG) in cattle brucellosis. AB - Results of the AG test with sera of normal cattle, and of those vaccinated with S19 strain, and of those with brucellosis were compared. Considerable effects of centrifugation (CF) on the agglutination serum titre have been observed. The usefulness of the AG test was discussed and given perspectives for future investigations. PMID- 3111522 TI - [Serological activity of anti-Brucella abortus immunoglobulins in the rose bengal plate test in cattle]. AB - The present study was to determine serological activity of cattle anti-Brucella antibodies in rose bengal plate test with regard to classical tests, i.e. standard agglutination test (SAT) and CFT (Complement Fixation Test). The serum containing antibodies of IgM class characteristic of the early stage of infection was taken from a calf on 13th day after the administration of Br. abortus S19 killed strain. The serum containing IgG antibodies (IgG1 and IgG2 subclasses) indicating the chronic brucellosis was taken from a cow infected naturally. IgM antibodies were isolated from serum by column chromatography on Sefadeks G-200 gel and IgG1 and IgG2 by column chromatography on DEAE cellulose. It was found out that IgM, IgG1, IgG2 were active in RBPT, SAT and IgM, IgG1 in CFT. The activity of anti-Brucella immunoglobulins in RBPT proves the possibility of diagnosing the above mentioned infections using this test. Taking into account titer height, in particular tests with certain Ig class, it can be said that acidic medium in RBPT reduces not selectively the activity of all immunoglobulin classes comparing with SAT and CFT, and that RBPT is typical qualitative test more valuable than SAT. The reduction of activity of all immunoglobulin classes in RBPT at significantly lower content of M immunoglobulin than IgG1 in the serum may explain the very high specificity of the test. Moreover, it was found that half the amount of the antigen in RBPT has a significant effect on the increase of test sensitivity. PMID- 3111523 TI - Internal motion and electron transfer in proteins: a picosecond fluorescence study of three homologous azurins. AB - We have carried out a picosecond fluorescence study of holo- and apoazurins of Pseudomonas aeruginosa (azurin Pae), Alcaligenes faecilis (azurin Afe), and Alcaligenes denitrificans (azurin Ade). Azurin Pae contains a single, buried tryptophyl residue; azurin Afe, a single surface tryptophyl residue; and azurin Ade, tryptophyl residues in both environments. From anisotropy measurements we conclude that the interiors of azurins Pae and Ade are not mobile enough to enable motion of the indole ring on a nanosecond time scale. The exposed tryptophans in azurins Afe and Ade show considerable mobility on a few hundred picosecond time scale. The quenching of tryptophan fluorescence observed in the holoproteins is interpreted in terms of electron transfer from excited-state tryptophan to Cu(II). The observed rates are near the maximum predicted by Marcus theory for the separation of donor and acceptor. The involvement of protein matrix and donor mobility for electron transfer is discussed. The two single tryptophan-containing proteins enable the more complex fluorescence behavior of the two tryptophans of azurin Ade to be understood. The single-exponential fluorescence decay observed for azurin Pae and the nonexponential fluorescence decay observed for azurin Afe are discussed in terms of current models for tryptophan photophysics. PMID- 3111524 TI - Modulation of thrombin-stimulated lipid responses in cultured fibroblasts. Evidence for two coupling mechanisms. AB - Treatment of cultured fibroblasts with thrombin results in the stimulation of cell division and lipid metabolism. Proteolytically active alpha-thrombin rapidly stimulates (a) release of arachidonic acid, (b) generation of inositol phosphates, and (c) increase in cellular diacylglycerol levels. Pretreatment of the fibroblasts with chymotrypsin before alpha-thrombin prevented the first two responses, (a) and (b), and reduced response c. Treatment of fibroblasts with gamma-thrombin, a proteolytic derivative of alpha-thrombin, produced a response indistinguishable from the alpha-thrombin treatment when preceded by chymotrypsin. These data support a model, similar to one for platelets [McGowan, E. B., & Detwiler, T. C. (1986) J. Biol. Chem. 261, 739-746], that fibroblasts possess two coupling mechanisms for the stimulation of lipid metabolism by thrombin. Similar to platelets, one mechanism, R1, mediates the stimulated release of arachidonic acid and is capable of activating Ni, a GTP-binding protein. R1 is inactivated by chymotrypsin and does not respond to gamma thrombin. The other mechanism, R2, responds to gamma-thrombin and is not activated by chymotrypsin. In contrast to the mechanisms proposed for platelets, we demonstrate that the phospholipase C responsible for the hydrolysis of phosphoinositides is not activated by R2 but is activated via R1. Importantly, stimulation of either mechanism results in the elevation of cellular diacylglycerol. This indicates that the stimulated elevation of diacylglycerol, or those events dependent upon the elevation of diacylglycerol, is not a reliable indicator for establishing the hydrolysis of phosphoinositides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111525 TI - Human platelet calmodulin-binding proteins: identification and Ca2+-dependent proteolysis upon platelet activation. AB - Calmodulin-binding proteins have been identified in human platelets by using Western blotting techniques and 125I-calmodulin. Ten distinct proteins of 245, 225, 175, 150, 90, 82 (2), 60, and 41 (2) kilodaltons (kDa) bound 125I-calmodulin in a Ca2+-dependent manner; the binding was blocked by ethylene glycol bis(beta aminoethyl ether)-N,N,N'N'-tetraacetic acid (EGTA), trifluoperazine, and nonradiolabeled calmodulin. Proteins of 225 and 90 kDa were labeled by antisera against myosin light chain kinase; 60- and 82-kDa proteins were labeled by antisera against the calmodulin-dependent phosphatase and caldesmon, respectively. The remaining calmodulin-binding proteins have not been identified. Calmodulin-binding proteins were degraded upon addition of Ca2+ to a platelet homogenate; the degradation could be blocked by either EGTA, leupeptin, or N ethylmaleimide which suggests that the degradation was due to a Ca2+-dependent protease. Activation of intact platelets by thrombin, adenosine 5'-diphosphate, and collagen under conditions which promote platelet aggregation (i.e., stirring with extracellular Ca2+) also resulted in limited proteolysis of calmodulin binding proteins including those labeled with antisera against myosin light chain kinase and the calmodulin-dependent phosphatase. Activation by the Ca2+ ionophores A23187 and ionomycin also promoted degradation of the calmodulin binding proteins in the presence of extracellular Ca2+; however, degradation in response to the ionophores did not require stirring of the platelet suspension to promote aggregation. Many Ca2+/calmodulin-regulated enzymes are irreversibly activated in vitro by limited proteolysis. Our data indicate that limited proteolysis of Ca2+/calmodulin-regulated enzymes also occurs in the intact platelet and suggest that the proteolysis is triggered by an influx of extracellular Ca2+ associated with platelet aggregation. PMID- 3111526 TI - Inhibition of NADH-ubiquinone reductase activity by N,N'-dicyclohexylcarbodiimide and correlation of this inhibition with the occurrence of energy-coupling site 1 in various organisms. AB - The NADH-ubiquinone reductase activity of the respiratory chains of several organisms was inhibited by the carboxyl-modifying reagent N,N' dicyclohexylcarbodiimide (DCCD). This inhibition correlated with the presence of an energy-transducing site in this segment of the respiratory chain. Where the NADH-quinone reductase segment involved an energy-coupling site (e.g., in bovine heart and rat liver mitochondria, and in Paracoccus denitrificans, Escherichia coli, and Thermus thermophilus HB-8 membranes), DCCD acted as an inhibitor of ubiquinone reduction by NADH. By contrast, where energy-coupling site 1 was absent (e.g., in Saccharomyces cerevisiae mitochondria and Bacillus subtilis membranes), there was no inhibition of NADH-ubiquinone reductase activity by DCCD. In the bovine and P. denitrificans systems, DCCD inhibition was pseudo first order with respect to incubation time, and reaction order with respect to inhibitor concentration was close to unity, indicating that inhibition resulted from the binding of one inhibitor molecule per active unit of NADH-ubiquinone reductase. In the bovine NADH-ubiquinone reductase complex (complex I), [14C]DCCD was preferentially incorporated into two subunits of molecular weight 49,000 and 29,000. The time course of labeling of the 29,000 molecular weight subunit with [14C]DCCD paralleled the time course of inhibition of NADH-ubiquinone reductase activity. PMID- 3111527 TI - Comparison of S100b protein with calmodulin: interactions with melittin and microtubule-associated tau proteins and inhibition of phosphorylation of tau proteins by protein kinase C. AB - To gauge similarities between S100b protein and calmodulin, interactions were observed between S100b and melittin and between S100b and tau, the microtubule associated proteins. The interaction of melittin with S100b protein in the presence and absence of calcium was studied by fluorescence polarization, UV difference spectroscopy, and sulfhydryl derivatization. Whether calcium was present or not in the solution, melittin and S100b form a complex of molar ratios up to 2:1. Further binding of melittin occurred, but it resulted in precipitation of S100b, as is true of the corresponding case of melittin binding to calmodulin. In the absence of calcium, the interaction of melittin and S100b shielded the tryptophan (Trp) of the former protein and exposed cysteine-84 beta (Cys-84 beta) of the latter protein, leaving the tyrosine-16 beta (Tyr-16 beta) of S100b unaffected. Calcium addition to the complex partially restored the exposure of Trp of melittin and caused changes in the environment of Tyr-16 beta (unlike the environmental changes induced for Tyr-16 beta by calcium in the absence of melittin). The conformational changes induced in S100b by interaction with melittin increased its affinity for calcium and offset the inhibition of calcium binding otherwise observed in the presence of potassium ions. This corroborated the previous finding that S100b affinity for calcium greatly depends on the protein conformation. The phenomena described above are similar to the interactions of melittin with calmodulin and thus suggest that S100b and calmodulin have a common structural domain not only that binds melittin but also that may interact with common target proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111528 TI - Catalytic versatility of Bacillus pumilus beta-xylosidase: glycosyl transfer and hydrolysis promoted with alpha- and beta-D-xylosyl fluoride. AB - Bacillus pumilus beta-xylosidase, an enzyme considered restricted to hydrolyzing a narrow range of beta-D-xylosidic substrates with inversion of configuration, was found to catalyze different stereochemical, essentially irreversible, glycosylation reactions with alpha- and beta-D-xylopyranosyl fluoride. The enzyme promoted the hydrolysis of beta-D-xylopyranosyl fluoride at a high rate, V = 6.25 mumol min-1 mg-1 at 0 degrees C, in a reaction that obeyed Michaelis-Menten kinetics. In contrast, its action upon alpha-D-xylopyranosyl fluoride was slow and characterized by an unusual relation between the rate of fluoride release and the substrate concentration, suggesting the possible need for two substrate molecules to be bound at the active center in order for reaction to occur. Moreover, 1H NMR spectra of a digest of alpha-D-xylosyl fluoride showed the substrate to be specifically converted to alpha-D-xylose by the enzyme. The observed retention of configuration is not consistent with direct hydrolysis by this "inverting" enzyme but is strongly indicative of the occurrence of two successive inverting reactions: xylosyl transfer from alpha-D-xylosyl fluoride to form a beta-D-xylosidic product, followed by hydrolysis of the latter to produce alpha-D-xylose. The transient intermediate product formed enzymically from alpha D-xylosyl fluoride in the presence of [14C]xylose was isolated and shown by its specific radioactivity and 1H NMR spectrum as well as by methylation and enzymic analyses to be 4-O-beta-D-xylopyranosyl-D-xylopyranose containing one [14C]xylose residue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111529 TI - Effect of isomers of swainsonine on glycosidase activity and glycoprotein processing. AB - The chemical synthesis of swainsonine [(1S,2R,8R,8 alpha R) trihydroxyindolizidine] from trans-1,4-dichloro-2-butene was previously described [Adams, C. E., Walker, F. J., & Sharpless, K. B. (1985) J. Org. Chem. 50, 420 424]. A modification of that synthesis provided two other isomers, referred to here as "Glc-swainsonine" [(1S,2S,8R,8 alpha R)-trihydroxyindolizidine] and "Ido swainsonine" [(1S,2S,8S,8 alpha R)-trihydroxyindolizidine]. To determine whether these new compounds had biological activity, they were compared to swainsonine as inhibitors of a number of commercially available glycosidases. While swainsonine is a potent inhibitor of jack bean alpha-mannosidase but does not inhibit other glycosidases, its two isomers were inactive on alpha-mannosidase but did inhibit other enzymes. Thus, Glc-swainsonine was an inhibitor of the fungal alpha glucosidase amyloglucosidase, and this inhibition was of a competitive nature (Ki = 5 X 10(-5) M) with respect to the substrate p-nitrophenyl alpha-D glucopyranoside. This alkaloid also inhibited beta-glucosidase, but much less effectively than alpha-glucosidase. On the other hand, Ido-swainsonine was more effective toward beta-glucosidase than toward alpha-glucosidase, and this inhibition was also of a competitive nature. None of these inhibitors were effective against beta-mannosidase or alpha- or beta-galactosidase. Glc swainsonine was also tested against the glycoprotein processing glycosidases. Surprisingly, in this respect, the alkaloid was like swainsonine in that it inhibited mannosidase II but had no effect or only slight effect on glucosidase I, glucosidase II, and mannosidase I. Glc-swainsonine also inhibited glycoprotein processing in cell culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111530 TI - Enzyme kinetics in solvents of increased viscosity. Dynamic aspects of carbonic anhydrase catalysis. AB - The dependence of enzymatic catalysis on diffusion rates in solution was examined with regard to high specific activity carbonic anhydrase (CA II) by varying the viscosity of the reaction medium with added glycerol, sucrose, and ficoll (a copolymer of sucrose and epichlorohydrin). Responses of the Michaelis-Menten parameters associated with CO2 hydration and HCO3- dehydration were deduced and analyzed by utilizing a spectrophotometric stopped-flow technique. It was found that both kcatHCO3 (= 3.9 X 10(5) s-1 at pH 5.90) and kcatCO2 (= 1.2 X 10(5) s-1 at pH 5.90 and 8.6 X 10(5) s-1 at pH 8.80) steadily decreased with the addition of monomeric viscogen while both KmHC03- (= 20 mM at pH 5.90) and KmCO2 (= 18 mM at pH 5.90 and 13 mM at pH 8.80) remained independent of viscosity, within experimental error. These results indicate that some kind of proton-transfer related event is primarily responsible for the observed rate decrease. The three polyhydroxy cosolutes exhibited significant differences with regard to the magnitude of the viscosity effect on the kcat of the enzyme, with glycerol affecting the largest decrease, sucrose affecting a moderate one, and ficoll having virtually no effect. The discrepancy between glycerol and sucrose could be largely reconciled by correcting for diffusion-unrelated effects as estimated from rate studies of considerably slower CA II catalyzed acetaldehyde hydration and p-nitrophenyl acetate hydrolysis. Ficoll, however, was found to be unsuitable as a viscogenic probe because it failed to appreciably decrease the mobilities of smaller ions (as deduced from electrolytic conductance measurements) despite its capacity to greatly increase the macroscopic viscosity of the medium. Our best estimates indicate that this reaction comes within ca. 30% of the diffusion limit at 0.890 cP and 25 degrees C for both CO2 hydration and HCO3- dehydration reactions. However, it is reasonable to expect this value to be considerably higher in the natural environment of the enzyme because of the relatively high viscosities attained in the interior of erythrocytes. PMID- 3111531 TI - Selective alteration of substrate specificity by replacement of aspartic acid-189 with lysine in the binding pocket of trypsin. AB - To test the role of Asp-189 which is located at the base of the substrate binding pocket in determining the specificity of trypsin toward basic substrates, this residue was replaced with a lysine residue by site-directed mutagenesis. Both rat trypsinogen and Lys-189 trypsinogen were expressed and secreted into the periplasmic space of Escherichia coli. The proteins were purified to homogeneity and activated by porcine enterokinase, and their catalytic activities were determined on natural and synthetic substrates. Lys-189 trypsin displayed no catalytic activity toward arginyl and lysyl substrates. Further, there was no compensatory change in specificity toward acidic substrates; no cleavage of aspartyl or glutamyl bonds was detected. Additional studies of substrate specificity involving gas-phase sequence analyses of digested natural substrates revealed an inherent but low chymotrypsin-like activity of trypsin. This activity was retained but modified by the Asp to Lys change at position 189. In addition to hydrolyzing phenylalanyl and tyrosyl peptide bonds, the mutant enzyme has the unique property of cleaving leucyl bonds. On the basis of computer graphic modeling studies of the Lys-189 side chain, it appears that the positively charged NH2 group is directed outside the substrate binding pocket. The resulting hydrophobic cavity may explain the altered substrate specificity of the mutant enzyme. The relatively low chymotrypsin-like activity of both recombinant enzymes may be due to distorted positioning of the scissile bond with respect to the catalytic triad rather than to the lack of sufficient interaction between the hydrophobic side chains and the substrate binding pocket of the enzyme. PMID- 3111532 TI - Stereoselective covalent binding of enantiomers of anti-benzo[a]pyrene diol epoxide to DNA as probed by optical detection of magnetic resonance. AB - Phosphorescence and optical detection of magnetic resonance measurements applied to the covalent adducts of (+)- and (-)-anti-benzo[a]pyrene with DNA show a marked red shift of the pyrenyl phosphorescence and a lowering of the zero field splitting parameters of the (-) adduct, relative to the (+) adduct and the (solvent-exposed) benzo[a]pyrene tetraol. These results are consistent with a predominance of quasi-intercalative sites in the (-) adduct and external, solvent exposed sites in the (+) adduct. PMID- 3111533 TI - The influence of unsaturation on the phase transition temperatures of a series of heteroacid phosphatidylcholines containing twenty-carbon chains. AB - A series of heteroacid sn-1,2 diacyl phosphatidylcholines (PC) with twenty-carbon fatty acyl chains has been synthesized. Each PC contained eicosanoate (20:0) in the sn-1 position and one of a group of eicosaenoic acids with increasing numbers of cis double bonds in the sn-2 position. The double bonds were at positions delta 11 (20:1), delta 11,14 (20:2), delta 11,14,17 (20:3), or delta 5,8,11,14 (20:4). The disaturated PC containing two eicosanoate chains was also studied. Aqueous dispersions of these PC were analyzed by differential scanning calorimetry, and data for the gel to liquid-crystalline transitions (given as PC: Tc (degrees C), Tmax (degrees C), delta H (kcal/mol)) were as follows - 20:0-20:0 PC: 66.8, 68.4, 15; 20:0-20:1 PC: 19.8, 22.2, 8; 20:0-20:2 PC: -4.3, 1.8, 5; 20:0 20:3 PC: 1.2, 4.4, 7; 20:0-20:4 PC: -10.7, -6.8, 3. Double bonds in excess of two per chain did not substantially change the transition temperatures of these heteroacid PC. There was a small effect of the location of the multiple double bonds on the transition temperature. The data is consistent with the model that the transition temperatures are determined by a balance between a decrease in the packing density in the gel and a decrease in the rotational freedom of the chains in the liquid crystal, both caused by the double bonds ((1983) Biochemistry 22, 1466-1473). PMID- 3111534 TI - Transport of the alpha-amino-mono-carboxylic acid L-alanine by the beta-alanine carrier of the rabbit ileum. AB - The proposal that the beta-alanine carrier of the rabbit ileum is a high affinity carrier of the neutral amino acids was examined by means of measurements of influx across the brush border membrane of the intact epithelium using L-alanine as a representative of the neutral amino acids. Confirming the proposal, evidence was provided for mutual competitive inhibition between beta-alanine and L alanine; and it was also demonstrated that a process contributes to the influx of L-alanine, which is characterized by a maximum rate of transport equal to that of beta-alanine and a Kt, which is equal to the Ki of L-alanine against the influx of beta-alanine. In the concentration range 0.01 to 0.125 mM the influx of L alanine was found to be linearly related to the concentration indicating a significant unstirred layer influence on present and previous estimates of the Kt values for influx of amino acids across the brush-border membrane of intact intestinal epithelia. PMID- 3111536 TI - Immunological properties of myosin light-chain kinases. AB - We have studied the immunological and structural properties of myosin light-chain kinases. Immunological studies were performed with affinity-purified antibodies to turkey gizzard smooth-muscle myosin light-chain kinase. Immunoprecipitation experiments demonstrated that avian smooth muscles contain a myosin light-chain kinase of Mr 130,000, whereas the enzyme immunoprecipitated from canine smooth muscles tested has an Mr of 150,000. These antibodies do not react with cardiac- or skeletal-muscle myosin light-chain kinases. Experiments performed with myosin light-chain kinases purified from turkey gizzards (Mr 130,000), bovine tracheal smooth muscle (Mr 160,000) and human platelets (Mr 100,000) demonstrated the following: the primary structures of the turkey gizzard and bovine tracheal enzymes appear to be quite different, based on one-dimensional peptide maps; only one-third as many antibodies bind to the bovine tracheal enzyme as compared to the turkey gizzard enzyme; the antibody:myosin light-chain kinase ratios for half maximal inhibition of all three enzymes are similar. Based on these data, we conclude that myosin light-chain kinases constitute an immunologically and structurally heterogeneous group of enzymes that have certain catalytic and regulatory properties in common. PMID- 3111535 TI - Decreased transport of D-glucose and L-alanine across brush-border membrane vesicles from small intestine of rats treated with mitomycin C. AB - To elucidate the mechanisms underlying the dysfunctions of intestinal absorption induced by antitumor drugs, the effect of pretreatment with mitomycin C on sodium gradient-dependent D-glucose and L-alanine transports was studied in rat brush border membrane vesicles. 24, 48, 96, or 120 h following a single intravenous injection of mitomycin C, brush-border membrane vesicles were prepared from rat small-intestines. The uptake of D-glucose and L-alanine was shown to be Na+ gradient-dependent even in the case of vesicles obtained from mitomycin C-treated rats, but uptake rates measured at 15 s and magnitude of overshooting effect in uptake of both solutes were decreased in vesicles maximally from 48 h mitomycin C treated rats. The rate of D-glucose uptake calculated at 15 s recovered to the control level in vesicles prepared at 96 h and 120 h after mitomycin C-treatment, indicating that the effect of mitomycin C on Na+ gradient-dependent D-glucose transport would be fully reversible. Tracer exchange experiments under Na+ and D glucose equilibrated conditions indicated that the Na+/D-glucose transporters were similarly operative in the vesicles from control and 48 h mitomycin C treated rats. Rates of 22Na+ uptake measured at 15 s in vesicles from 48 h mitomycin C-treated rats, however, were increased. The increased permeability to Na+ might bring about a more rapid dissipation of the Na+ gradient in these vesicles and this would secondarily cause the decrease in Na+-dependent D-glucose uptake in vesicles from mitomycin C-treated rats. PMID- 3111537 TI - Chemical and enzymatic oxidation of 4-methylcatechol in the presence and absence of L-serine. Spectrophotometric determination of intermediates. AB - A pathway for 4-methylcatechol oxidation by tyrosinase (monophenol, dihydroxy-L phenylalanine:oxygen oxidoreductase, EC 1.14.18.1) in the presence of L-serine is proposed. Characterization of intermediates in this oxidative reaction and stoichiometry determination have both been performed. It has been possible to detect spectrophotometrically 4-methyl-o-benzoquinone as the first intermediate in this pathway after oxidizing 4-methylcatechol with epidermis tyrosinase or sodium periodate at pH 6.5. The steps for 4-methylcatechol transformation in the presence of L-serine could be: 4-methylcatechol----4-methyl-o-benzoquinone----5 methyl-4N-serine-catechol----5 - methyl-4N-serine-o-benzoquinone. Matrix analysis of the spectra obtained with a rapid-scan spectrophotometer verified that 4 methyl-o-benzoquinone was transformed into 5-methyl-4N-serine-o-benzoquinone at a constant ratio, the stoichiometry for this conversion being the equation: 2-(4 methyl-o-benzoquinone) + L-serine----4-methylcatechol + 5-methyl-4N-serine-o benzoquinone. PMID- 3111538 TI - Enzymatic oxidation by frog epidermis tyrosinase of 4-methylcatechol and p cresol. Influence of L-serine. AB - A study has been made of the kinetics of cresolase and catecholase activities of tyrosinase on the p-cresol/4-methyl-catechol pair in the presence of L-serine. For this, a spectrophotometer assay for both activities based on the spectrophotometric and stoichiometric characteristics of the chemical reactions in the evolution of 4-methyl-o-benzoquinone is proposed. The presence of L-serine in the reaction medium caused a modification in the lag period and the steady state rate expressed during the cresolase activity of tyrosinase, but no modification was observed during the expression of catecholase activity. These results can be explained taking into account the complex mechanism proposed for tyrosinase which included the chemical steps involved in the process. Furthermore, a singular form of regulation of enzymatic activity by L-serine has been clarified, not by any direct interaction between the protein molecule and the nucleophile, but by modification of the chemical reactions involved in the mechanism of tyrosinase. PMID- 3111539 TI - The role of apolipoprotein A-I and apolipoprotein A-II in high-density lipoprotein binding to human adipocyte plasma membranes. AB - Adipocyte plasma membranes purified from omental fat tissue biopsies of massively obese subjects possess specific binding sites for high-density lipoprotein (HDL3). This binding was independent of apolipoprotein E as HDL3 isolated from plasma of an apolipoprotein E-deficient individual was bound to a level comparable to that of normal HDL3. To examine the importance of apolipoprotein A I, the major HDL3 apolipoprotein, in the specific binding of HDL3 to human adipocytes, HDL3 modified to contain varying proportions of apolipoproteins A-I and A-II was prepared by incubating normal HDL3 particles with different amounts of purified apolipoprotein A-II. As the apolipoproteins A-I-to-A-II ratio in HDL3 decreased, the binding of these particles to adipocyte plasma membranes was reduced. Compared to control HDL3, a 92 +/- 3.1% reduction (mean +/- S.E., n = 3) in maximum binding capacity was observed along with an increased binding affinity for HDL3 particles in which almost all of the apolipoprotein A-I had been replaced by A-II. The uptake of HDL cholesteryl ester by intact adipocytes as monitored by [3H]cholesteryl ether labeled HDL3, was also significantly reduced (about 35% reduction, P less than 0.005) by substituting apolipoprotein A-II for A-I in HDL3. These data suggest that HDL binding to human adipocyte membranes is mediated primarily by apolipoprotein A-I and that optimal delivery of cholesteryl ester from HDL to human adipocytes is also dependent on apolipoprotein A-I. PMID- 3111540 TI - Bacillus cereus phospholipase C: carboxylic acid ester specificity and stereoselectivity. AB - Thiophosphate analogs of phosphatidylcholine have been synthesized with varying structural complexity. These analogs have been used in a continuous spectrophotometric assay for phospholipase C (Bacillus cereus) to estimate the minimal structural requirements associated with the non-polar portion of the substrate phospholipid. The analogs were of three types containing zero, one or two carboxylic acid ester functionalities. The analogs with one or two ester groups acted as substrates for phospholipase C, while those without an ester functionality were not hydrolyzed. The rac-phosphatidylcholine analog with two ester functionalities gave biphasic time-course results, and was subsequently resolved into enantiomers by selective hydrolysis with a sterospecific phospholipase A2 (Crotalus atrox). The enantiomer with R absolute configuration was rapidly hydrolyzed by the phospholipase C while the enantiomer with the S configuration was slowly hydrolyzed after a long induction period. The results suggest that the B. cereus phospholipase C is specific for an ester functionality and is stereoselective for the R absolute configuration at glycerol C-2. PMID- 3111541 TI - Evidence for the release of arachidonic acid through the selective action of phospholipase A2 in thrombin-stimulated human platelets. AB - The release of arachidonic acid from thrombin-stimulated platelets can be attributed to the action of phospholipase A2 on membrane phospholipid. Previously, analysis of individual subclasses of phospholipid demonstrated that 1 acyl-2-[3H]arachidonoyl-sn-glycerophosphocholine and to a lesser degree 1-acyl-2 [3H]arachidonoyl-sn-glycerophosphoethanolamine were the main source of [3H]arachidonic acid in thrombin-stimulated cells. In the present work, 1,2 diacyl phospholipid subclasses were analyzed as 1,2-diacylglycerobenzoates by high-pressure liquid chromatography in order to analyze arachidonate release as mass changes in individual molecular species of phospholipid. Following thrombin stimulation (5 U/ml, 5 min, 37 degrees C) all arachidonoyl-containing molecular species of 1,2-diacyl-sn-glycerophosphocholine decreased in mass and [3H]arachidonate content by almost 50%, while those of 1,2-diacyl-sn glycerophosphoethanolamine decreased by 20%. The mass change was substantial and indicated that these phospholipids are a major source of arachidonate in stimulated cells. No variation was seen in the other non-arachidonate-containing molecular species of either subclass. Thus, deacylation of membrane 1,2 diacylglycerophosphocholine and 1,2-diacylglycerophosphoethanolamine by phospholipase A2 is selective for those molecular species of phospholipid containing arachidonic acid, suggesting that a certain proportion of arachidonoyl containing molecular species of phospholipid are compartmentalized with the platelet membrane proximal to the site of action of this enzyme. These studies demonstrate that the human platelet is a cell poised and specialized to release rapidly substantial amounts of arachidonic acid upon stimulation. PMID- 3111543 TI - Hydrolysis of galactosylsphingosine and lactosylsphingosine by beta galactosidases in human brain and cultured fibroblasts. AB - Enzymatic properties of beta-galactosidases with galactosylsphingosine (psychosine) and lactosylsphingosine as the substrates were examined. Although bile salts were stimulatory on the hydrolysis of the glycolipids in normal brain and cultured fibroblasts, the hydrolytic activities could be readily assayed, without detergents. The in vitro hydrolysis of lactosylsphingosine in cultured fibroblast homogenates was catalyzed by two enzymes, as is the case with the hydrolysis of galactosylceramide and lactosylceramide. Lactosylsphingosine beta galactosidase activities assayed in the absence and the presence of taurocholate (probably lactosylceramidase I) were deficient in fibroblasts from patients with globoid cell leukodystrophy, while the activity assayed with sodium cholate (probably lactosylceramidase II) was deficient in GM1 gangliosidosis fibroblasts. In contrast, galactosylsphingosine beta-galactosidase was not activated by cholate and the enzyme activities assayed with the no-additive and taurocholate systems were deficient in brain and fibroblasts from patients with globoid cell leukodystrophy, thereby indicating that the hydrolysis of galactosylsphingosine is catalyzed by one enzyme, galactosylceramidase I. Exogenous lipids and an activator protein purified from normal spleen activated galactosylsphingosine beta-galactosidase but they were inhibitory to lactosylsphingosine beta galactosidase. Because the Km values of lactosylsphingosine beta-galactosidase assayed with cholate were several magnitude higher than those obtained with the no-additive system and because lactosylsphingosine is readily hydrolyzed with the no-additive system in vitro, it is likely that the in vivo hydrolysis of the lipid is catalyzed by only one enzyme, lactosylceramidase I. PMID- 3111544 TI - Thiamin uptake in Euglena gracilis. AB - Thiamin uptake has been investigated in Euglena gracilis Z. This protozoon possessed an active transport system for thiamin with a Km value of 17 nM and a Vmax value of 7.8 pmol per 10(6) cells per min. Thiamin uptake was dependent on pH and temperature, but not on exogenous glucose as an energy source. Oxythiamin and pyrithiamin were competitive inhibitors with Ki values of 33 nM and 15 nM, respectively. Thiamin monophosphate, thiamin pyrophosphate, thiamin triphosphate, heteropyrithiamin, quinolinothiamin, thiamin chloride and amprolium inhibited uptake. Inhibition of thiamin uptake by various metabolic inhibitors and anaerobiosis suggest that thiamin uptake requires an energy source generated by respiration and glycolysis. PMID- 3111542 TI - Immunological detection of low-density lipoproteins modified by malondialdehyde in vitro or in vivo. AB - We describe an ELISA technique able to recognize malondialdehyde-modified low density lipoproteins (LDL). For this purpose we produced antibodies to malondialdehyde-LDL, specific for the malondialdehyde modification of LDL; these antibodies recognized essentially malondialdehyde-LDL. Coating ELISA plates with the antibodies to malondialdehyde-LDL and using peroxidase-labelled antibodies to LDL, which reveal only apolipoprotein B, we obtained an accurate method of detecting malondialdehyde-modified apolipoprotein B. Preliminary studies demonstrated that this method allows the detection of lipoproteins containing malondialdehyde-modified apolipoprotein B in the serum of patients with cardiovascular diseases. PMID- 3111545 TI - Proto-oncogenes. PMID- 3111546 TI - Lipid biodynamics: new perspectives [published errtum appears in Biochimie 1987 May;69(5):558]. AB - Active biological systems can be divided into five phases: the aqueous polar phase, the monolayer and/or bilayer interfacial phase, the apolar or hydrophobic phase, the solid or insoluble phase and the gaseous phase. The micellar phase is a special dispersed state of an interfacial phase. Molecules are distributed among these five phases according to their physicochemical properties. Herein is proposed a standardization in strict compliance with the CGS (cm, g, s) unit system and uses the mass/volume, mole per cm3 (mol X cm-3) chemical unit. This standardization requires a new set of symbols to clearly distinguish the concentrations in the different phases. The numerous implications of this standardization are discussed with respect to the quantitative classification of lipids based upon interphase partition coefficients, a new definition of micelles, simple models for the study of lipid biodynamic behavior and sites of action of lipid metabolism enzymes as well as determination of the physicochemical parameters of circulating lipoproteins. By compartmentalization in an aqueous polar phase, an interfacial phase comprising phospholipids and free cholesterol and an apolar phase comprising triglycerides and esterified cholesterol, this standardization will greatly simplify quantitative research on the factors regulating and disturbing cholesterol homeostasis. The notion of total cholesterol must be foresaken, since the biodynamic behavior of free cholesterol and esterified cholesterol are fundamentally different. Free cholesterol shares the fate of the interfacial phase of which it is a part, this fate being hinged on enzymatic biotransformations and/or ligand--receptor interactions. The proposed standardization gives rise to a new rationale using simple calculations and its advantage will be 2-fold: first, in the design of experimental protocols; and second, in allowing immediate and unambiguous comparison of experimental data based upon strictly defined parameters. PMID- 3111547 TI - Lactate dehydrogenase activity in the mitochondrial fraction of chicken liver: enzyme binding and kinetic behavior of soluble and bound enzyme. AB - Chicken liver crude mitochondrial fraction showed lactate dehydrogenase activity (6.5% of cytoplasmic enzyme). Most of the mitochondrial lactate dehydrogenase was solubilized by sonication of the mitochondrial fraction in 0.15 M NaCl, pH 6. Total extracted lactate deshydrogenase activity was 3-fold higher than the initial pellet activity. Different isoenzymatic compositions were observed for cytosoluble and mitochondrial extracted lactate dehydrogenase. The pI, values of the 5 lactate dehydrogenase isoenzymes were found to be independent of their origin. The cytosoluble lactate dehydrogenase and the separated H4,H3M and H2M2 isoenzymes were able to bind to the chicken liver mitochondrial fraction in 5 mM sodium phosphate buffered medium, and could be solubilized afterwards with 0.15 M NaCl, pH 6. The enzyme bound to the mitochondrial fraction was less active than the soluble one. Particle saturation by the bound enzyme occurred with all mitochondrial fractions assayed. According to the Langmuir isotherm, the non sonicated mitochondrial fractions contain a single type of binding sites for lactate dehydrogenase; in contrast, the sonicated mitochondrial fraction should contain different binding sites. Chicken liver crude or sonicated active mitochondrial fractions showed a hyperbolic behavior with respect to NADH and a non-hyperbolic one with respect to pyruvate. This mechanism is different from the bi-bi compulsory order mechanism of the soluble enzyme. With hydroxypyruvate as the substrate, the active mitochondrial fraction fit a sequential mechanism but lost the rapid-equilibrium characteristics of the soluble enzyme. PMID- 3111548 TI - Expression vectors based on the Agrobacterium rhizogenes Ri plasmid transformation system. AB - This article describes several new expression vectors that capitalize on the ability of Agrobacterium rhizogenes to transfer DNA from its Ri plasmid to the plant nuclear genome. The intermediate vectors described include an expression cassette based on one of the three following promoters: the nopaline synthase promoter, or the cauliflower mosaic virus (CaMV) promoters responsible for transcription of either the 19S or 35S CaMV RNA. The termination and polyadenylation signals are either from the nopaline synthase gene or from CaMV. The expression micro-Ri plasmid described bears a selectable marker gene and an expression cassette cloned between the borders of the TL-region of the Ri plasmid of A. rhizogenes A4. Different strategies for using these vectors to introduce chimeric genes into plants are described, and the advantages and disadvantages of the two types of vectors are discussed. PMID- 3111549 TI - Partial characterization of intracellular and secreted glycosidases from rabbit articular chondrocytes in culture. AB - N-Acetyl-beta-hexosaminidase, beta-galactosidase and beta-glucuronidase activities were shown to be present in cultured rabbit articular chondrocytes. Secretion of enzyme activity seems to preferentially result in the accumulation of N-acetyl-beta-hexosaminidase. Three days after seeding, the amount of N-acetyl beta-hexosaminidase activity found in the medium accounts for about 140% of the total N-acetyl-beta-hexosaminidase activity after complete disruption of the cell pellet. Optimal conditions of incubation time, cell numbers, substrate concentration, and pH for glycosidase activities were determined in 0.1% Triton X 100. Intracellular and secreted glycosidases have shown similar elution profiles by chromatofocusing. N-acetyl-beta-hexosaminidase exhibits two major forms which may play a role in the catabolism of glycosaminoglycans. PMID- 3111550 TI - Intracellular phospholipase activity in rat heart: comparison between endogenous and exogenous substrates. AB - Two methods were used to estimate the intracellular phospholipase activity in rat heart: one using exogenous radioactive substrate dispersed as unilamellar vesicles; the other using endogenous membrane hydrolysis and subsequent phospholipid and lysophospholipid separation by high-performance liquid chromatography and quantification by phosphorus determination. We found that the endogenous method provided a higher hydrolysis rate than the exogenous method and that phosphatidyl ethanolamine was a better substrate than phosphatidyl choline. PMID- 3111552 TI - [Factor and cluster analysis on the study of mimetic communication in monkeys]. AB - The mimics elements, typical mimic complexes and frequency of mimics display in different behavioral contexts in representatives of 10 species of monkeys and apes have been investigated. The methods of factor and cluster analyses have been applied to reveal a connection between mimics and phylogenetical level of the species. A dendrogram of interspecies relationships is presented. The type of species social structure is one of the main factors in mimic communication development. PMID- 3111551 TI - Histidine-rich protein in rodent malaria. AB - Mouse red blood cells (RBCs) infected with the malaria parasite Plasmodium yoelii nigeriensis were shown to synthesize a histidine-rich protein (His-RP) in vitro. The existence of this protein was demonstrated by comparing fluorograms of infected red blood cells (IRBCs) labelled with either [14C]histidine or [14C]leucine. The molecular weight of this His-RP was estimated to be 43,500, which compares well with the values reported for the avian parasite P. lophurae (45,000) and for the human parasite P. falciparum (42,000). This result supports the idea that such a protein may play an important role in the biology of all plasmodium species. PMID- 3111553 TI - Decreased plasma arachidonic acid binding capacity in neonates. AB - Arachidonic acid (AA) metabolites have been implicated in neonatal pathologic states such as respiratory distress syndrome (RDS). Since free (nonprotein bound) AA is the substrate for synthesis of these compounds, a decreased capacity to bind AA in neonatal plasma could contribute to these disorders. AA binding was assayed by equilibrium dialysis in plasma samples from healthy adults and various infant groups. Plasma from these infant groups bound significantly less AA than adult plasma. Premature infants with RDS and premature infants receiving intralipid had the lowest capacity to bind AA. The increased availability of free AA may be important in neonatal pathophysiologic states involving arachidonate metabolites. PMID- 3111554 TI - The effect of lithium on the membrane molecular dynamics of normal human erythrocytes. AB - Erythrocytes from normal adults with no personal or family history of bipolar affective disorder were analyzed by fluorescence spectroscopy to determine what effect, if any, acute in vitro incubation with lithium had on erythrocyte membrane dynamics. The effects on erythrocyte membrane molecular dynamics of varying concentrations of Li2CO3 (0.25-2.0 meq/liter), varying incubation temperatures (25-40 degrees C), and varying incubation times (5-185 min) were investigated. Following incubation with Li2CO3, the erythrocytes were labeled with either 4-phenylspiro-[furan-2(3H),--1'phthalan]--3,3'-dione (fluorescamine), which binds to membrane surface primary amines, or 12(9)anthroyl stearate [12(9)AS], which inserts deep in the membrane hydrocarbon core. The membrane molecular dynamics were then determined by fluorescence anisotropy measurements. These studies demonstrate that clinically relevant concentrations of Li+ incubated with intact normal human erythrocytes significantly alters molecular dynamics on the erythrocyte membrane surface, with less striking changes in the hydrocarbon core. A possible interpretation of these findings is that hydrated Li+ alters the electrostatic interaction of membrane surface molecules, as well as the surrounding solvent (water) structure, with a resultant increase in the molecular motion of these molecules. Alterations in membrane receptor motion could potentially alter receptor functional activity. If similar motional alterations were to occur in the interior of a membrane channel, such as an ionophore, the functional activity of the channel could also be potentially altered. These findings provide additional insight into possible biological actions of Li+, as well as potential molecular alterations in bipolar affective disorder erythrocytes. PMID- 3111555 TI - The extension rate independence of the hysteresis in glutaraldehyde-fixed bovine pericardium. AB - Glutaraldehyde-fixed bovine pericardium demonstrates both relaxation of stress and hysteresis during uniaxial loading and unloading. These phenomena suggest viscoelastic behaviour of the material. This study uses analysis of variance to test statistically the hypothesis that the chemically modified pericardium possesses a 'fading memory' for the history of previous load procedures and that the hysteresis is extension rate independent. PMID- 3111556 TI - An assist device for selective reduction of the work of breathing. PMID- 3111557 TI - Kinetics and mechanism of anionic ligand binding to carbonic anhydrase. AB - The kinetics of complex formation between Co(II)-carbonic anhydrase B and the anions cyanate, thiocyanate and cyanide has been studied at different pH values employing temperature-jump relaxation spectrometry. Formation of the 1:1 complex occurs via binding of the deprotonated state of the anion to an acidic state of the enzyme. The determined formation rate constants range from 10(8) to 3 X 10(9) M-1 s-1 and are two to three orders of magnitude higher than the value estimated for a ligand coordination to the central Co2+, based on a solvate substitution mechanism. These kinetic results strongly indicate that the deprotonated anion binds to an unoccupied coordination position of the protein-bound heavy metal ion in the form of an addition reaction. Upon binding of the anion, the coordination number of the Co2+ in the acidic state of the enzyme is increased from four to five. In the case of cyanide, a 2:1 anion complex is also formed. The formation rate constant is 5 X 10(5) M-1 s-1 which provides good evidence that this binding process is controlled by a solvate substitution mechanism. PMID- 3111558 TI - Protein dynamics. A time-resolved fluorescence, energetic and molecular dynamics study of ribonuclease T1. AB - Studies using time-resolved fluorescence depolarization were performed on the internal motion of Trp 59 of ribonuclease T1 (EC 3.1.27.3) in the free enzyme, 2' GMP-enzyme complex and 3'-GMP-enzyme complex. The Trp 59 motion was also studied in the free enzyme using molecular dynamics simulations. Energetic analysis of activation barriers to the Trp 59 motion was performed using both the transition state theory and Kramers' theory. The activation parameters showed a dependence on solvent viscosity indicating the transition state approach in aqueous solution to be inadequate. When taking solvent viscosity contributions into account agreement between the transition state and Kramers' theories was obtained. The results indicate the three enzyme forms to have different conformations with the free enzyme and 3'-GMP-enzyme complex being similar. Comparison of the experimental and theoretical results showed a good agreement on the Trp 59 motion in the free enzyme. Trp 59 appears to vibrate rapidly, with a relaxation time of the order of 1 ps, within free space in the protein matrix and to have a slower motion, with a relaxation time of the order of 100 ps, which is related to breathing of the surrounding protein matrix. Molecular dynamics results indicate high mobility in regions of the enzyme involved in the interaction with the guanine base of the inhibitor or substrate while much lower mobility occurred in residues involved in the catalytic mechanism of ribonuclease T1. PMID- 3111559 TI - Kinetic study of the transient phase of a chemical reaction system coupled to an enzymatically catalyzed step. Application to the oxidation of epinine by tyrosinase. AB - The present work deals with epinine oxidation by mushroom tyrosinase and sodium metaperiodate. Intermediates produced within short reaction times were characterized by repetitive scanning spectrophotometry and the stoichiometry of the appearance of the respective aminochrome was established. The oxidation pathway from epinine to aminochrome had the following steps: epinine----o-quinone H+----o-quinone----leukoaminochrome----aminoc hrome. The stoichiometry for the conversion of o-quinone-H+ into the aminochrome of epinine followed the equation: 2 o-quinone-H+----epinine+aminochrome. A transient phase kinetic study has been developed for the system of chemical reactions coupled to an enzymatically catalyzed step, these taking place when epinine is oxidized by mushroom tyrosinase. Rate constants for the implied chemical steps at different temperature and pH values were calculated from analysis of the progress curves of aminochrome accumulation with time. The thermodynamic activation parameters of the chemical steps were also calculated. PMID- 3111560 TI - High serum levels of soluble interleukin 2 receptor in patients with B chronic lymphocytic leukemia. AB - By using an enzyme-linked immunosorbent assay, the presence of the soluble form of the interleukin-2 receptor (sIL-2R) was evaluated in the peripheral blood of 54 patients with B cell chronic lymphocytic leukemia (B-CLL). Serum levels of sIL 2R were correlated with clinical features, relevant hematologic and immunological data, and in some cases, with in vitro functional studies. In 51 patients (94.4%), the levels of sIL-2R were increased as compared with normal age-matched controls (1,781 U/mL +/- 231 v 276 U/mL +/- 26, respectively; P less than .001). Although this increase was observed in all stages of the disease and independently of several hematologic and immunologic parameters, a trend toward lower levels of sIL-2R was documented in patients with a less-invasive disease. When the values were correlated with the functional status of the residual T cell population, it was found that patients with the lowest levels of sIL-2R showed the best mitogenic response and helper capacity. It is suggested that in B-CLL patients the high levels of serum sIL-2R, capable of binding to its ligand, may block the T cell-produced IL-2, thus contributing toward a defective physiological action by this lymphokine. In turn, this defective availability of IL-2 may play a part in the abnormal immunoregulation that is implicated in the hypogammaglobulinemia, susceptibility to infections, and incidence of second neoplasias often observed in this disease. PMID- 3111561 TI - Isolation, characterization, and localization of glycosaminoglycans in rabbit bone marrow. AB - The glycosaminoglycans that exist in rabbit bone marrow were analyzed chemically, and their in situ localization was studied immunohistochemically. Femoral bone marrow of 3-month-old rabbits was defatted with organic solvents. Glycosaminoglycans were prepared from the defatted tissue after its digestion with pronase, treatment with mild alkali, and then digestion with DNase-I. The tissue contained glycosaminoglycans equivalent to 195 mg of hexosamine per femur, which accounted for 27.3% of the total hexosamine in the tissue. Studies with hyaluronidase from Streptomyces hyalurolyticus and chondroitinase ABC showed that the glycosaminoglycans were composed of hyaluronic acid (16% of the total glycosaminoglycan) and chondroitin 6-sulfate (79%). The chondroitin 6-sulfate was separated on Bio-Gel A-0.5m gel into two molecular species with mol wt of greater than 12,000 (Kd greater than 0.2) and approximately 8,000 (Kd = 0.47). Bone marrow digested with chondroitinase ABC and then treated with three monoclonal antibodies 4/8/9-A-2, 5/6/3-B-3, and 5/6/1-B-5, which were specific for unsaturated 4-sulfated, 6-sulfated, and nonsulfated disaccharide structures, respectively, at the nonreducing end of chondroitin sulfate chains, reacted with only 5/6/3-B-3. This result indicated that the chondroitin sulfate, isomer in the bone marrow is chondroitin 6-sulfate, consistent with the biochemical results. The chondroitin 6-sulfate was localized mainly in the extracellular compartment and was considered to be involved in construction of the hemopoietic microenvironment in the bone marrow. PMID- 3111562 TI - Hemophilia A: carrier detection and prenatal diagnosis by DNA analysis. AB - In this study, we used DNA polymorphisms for carrier detection and prenatal diagnosis of hemophilia A in a large group of Italian families. The restriction fragment length polymorphisms (RFLPs) investigated were the intragenic polymorphic Bc/I site within the factor VIII gene; the extragenic multiallelic Taq I system at the St14 locus; and the extragenic Bg/II site at the DX13 locus. The factor VIII probe was informative in 30%, St14 in 82%, and DX13 in 60% of obligate carriers. The combination of factor VIII-Bc/I and St14-Taq I showed that 91% of obligate carriers were heterozygotes for one or both; with all three probes, only 4% of obligate carriers were noninformative. In families clearly segregating for hemophilia A, RFLP analysis allowed us to define the carrier status for the hemophilia A gene in all 27 women tested. RFLP analysis allowed us to exclude the carrier status in 39 of 45 female relatives of sporadic patients. The combination of RFLP analysis and biological assay of factor VIII allowed us to identify a de novo mutation in the maternal grandfather in 7 of 12 of the families with sporadic cases, for which members of three generations were available for study. Nine of 10 couples requesting prenatal diagnosis provided informative RFLP DNA pattern. Carrier status was excluded in two women, two fetuses were shown to be female, and prenatal diagnosis was carried out in five pregnancies by DNA analysis. Prenatal testing was successful in three instances and failed in two because a sufficient amount of chorionic villous DNA was not obtained for the analysis. PMID- 3111563 TI - Blood cells participate in the fibrinolytic response to tissue-type plasminogen activator. AB - Exercise and venous occlusion stimulate fibrinolysis. In addition to increased concentrations of tissue-type plasminogen activator (tPA) and increased plasmin mediated fibrinolysis in plasma, these stimuli produce additional cellular-phase activity in blood that is of the same magnitude as the plasma response. To determine whether tPA alone, rather than other consequences of these stimuli, is responsible for the cellular response, the in vitro effects of tPA on whole blood, plasma, and calculated cellular-phase (whole blood minus plasma) activities were determined by solid-phase radiofibrin assay on venous blood from ten normal subjects (seven men, three women). At tPA concentrations encompassing physiological and therapeutic levels (5 to 100 ng/mL; 0.7 to 14 IU/mL), increments in whole blood were consistently in excess of those in companion plasma and represented increased cellular-phase activity equivalent in magnitude to the well-known increase in plasma activity. Fibrinolytic activity produced by 10 to 20 ng tPA/mL (1.4 to 2.8 IU/mL) was consistently detected in whole blood and plasma by 60 minutes, with higher concentrations (100 ng or 14 IU tPA/mL) detectable after a five-minute assay in all subjects. Thus, tPA alone, without invoking fibrinolytic factors extraneous to blood or other effects of exercise or venous occlusion, accounts for both cellular and plasma responses to these stimuli. The considerable cellular response, the mechanism of which remains to be elucidated, may constitute a determinant of individual therapeutic responsiveness to tPA. PMID- 3111564 TI - Effect of lipopolysaccharides on cultured human endothelial cells. Relationship between tissue factor activity and prostacyclin release. AB - Exposure to lipopolysaccharides (LPS; 10 micrograms/ml derived from either S. enteritidis or E. coli or to their lipid A moiety alone induced procoagulant activity in cultured human endothelial cells. This exclusively cell-associated activity was identified as tissue factor activity by two criteria: Firstly, the presence of Factor VII was required for its expression and, secondly, clotting was abolished by the addition of the IgG fraction of anti-human tissue factor antibodies. Concomitant analysis of prostacyclin (PGl2) formation by the cells showed a substantial increase in the production of this potent platelet inhibiting substance during exposure to endotoxin. LPS-induced release of PGl2 did not result in refractoriness of the cells to generate new PGl2 as indicated by the retained response to stimulation with 20 microM arachidonic acid. While the release of PGl2 could be inhibited by pretreatment of the cells with 100 microM acetylsalicylic acid (ASA), the induction of tissue factor activity remained unaffected by ASA. In contrast to LPS-free control cultures, ASA did not completely prevent PGl2 formation by human endothelial cells after exposure to LPS suggesting the induction of a cyclooxygenase-independent pathway by LPS. PMID- 3111565 TI - Lymphocyte subpopulations in peripheral blood and bone marrow in patients with idiopathic myelofibrosis. AB - In 8 patients with idiopathic myelofibrosis (IM) T and B cells were studied in view of the possibility that immunological dysfunctions are involved in initiating or contributing to the bone marrow fibrosis. In peripheral blood the absolute numbers of E-SRBC and OKT3+ lymphocytes were significantly reduced; in addition a significant decline was observed in the proportion and absolute numbers of OKT8+ cells, resulting in a reversed Leu-3a/OKT8 ratio. An impaired B cell function was observed in 4 of the 8 patients, characterized by a disturbed in vitro pokeweed mitogen stimulated immunoglobulin synthesis and low serum immunoglobulin levels. Immuno-histological studies of the bone marrow demonstrated a scarcity of T cells but normal numbers of B cells. However, no correlation was noted between the observed deviations of B and T cells and the degree of bone marrow fibrosis determined by means of bone marrow histology and serum procollagen-III levels. These data are not sufficient to support the hypothesis that immunological changes in IM are primarily involved in the process of bone marrow fibrosis. PMID- 3111566 TI - The haemostatic function of the vascular endothelial cell. PMID- 3111567 TI - Environmental fate of Dimilin 25-W in a central Appalachian forest. PMID- 3111569 TI - Ventilation during carbon dioxide loading in anaesthetized women. AB - The mechanisms whereby arterial carbon dioxide tension (PaCO2) remains constant despite varying rates of CO2 production are poorly understood. During the gynaecological operation of laparoscopy, the abdominal cavity is filled with CO2. An increase in the rate of CO2 delivery to the lung (less than 50%) occurs as a result of venous CO2 absorption. Respiratory control in 39 anaesthetized but spontaneously breathing women was studied during such exogenous CO2 loading. End tidal CO2 tension (PACO2 - rapid infrared analyser) and minute-ventilation (Wright respirometer) were measured before and at 5 min intervals after peritoneal insufflation. Ventilation increased and mean PACO2 remained constant in these patients. Inhalational anaesthetics depress respiration and this was confirmed by raised control PACO2 values in this study. However, it appears that mechanisms underlying PACO2 homeostasis in the presence of a CO2 load are not depressed by inhalational anaesthetic in this study. These patients were probably hyperoxic. Peripheral arterial chemoreflexes are thought to be eliminated by hyperoxia. Therefore, it is likely that neural stimuli, from exploration of the abdomen, drove breathing. Furthermore, the fact that there was not a large fall in PACO2 may have been due to feedback via the central (brainstem) chemoreceptor. PMID- 3111568 TI - Fate of 7,12-dimethylbenz(a)anthracene in rainbow trout, Salmo gairdneri. PMID- 3111570 TI - Reference values for gas exchange during exercise in healthy nonsmoking and smoking men. AB - The gas exchange at rest and during exercise was measured in 50 healthy men, 25 lifelong nonsmokers and 25 smokers, between 20 and 65 years of age. Arterial blood samples were taken and expired air was collected at rest, supine and sitting, and during graded exercise. Prediction formulas for various gas exchange variables were obtained by multiple regression. Optimal conditions for gas transfer were present at light exercise. The arterial oxygen tension (PaO2) remained approximately constant during exercise, although in individual smokers and nonsmokers it decreased by up to 1.8 kPa (13.5 mmHg) between a workload of 50 W and the maximal workload. The lower limit for PaO2 at maximal exercise was about 10.7 kPa (80 mmHg). The alveolo-arterial difference in oxygen tension (PA aO2) increased considerably with increased workload, from 1.09 +/- 1.05 kPa at 50 W to 3.1 +/- 0.9 kPa at maximal exercise. Ageing and tobacco smoking were associated with a decrease in PaO2 and an increase in PA-aO2 at rest in the supine position, but at maximal exercise neither PaO2 nor PA-aO2 was significantly influenced by age or tobacco smoking. In contrast, the dead space and total ventilation were increased during exercise by ageing and tobacco smoking. PMID- 3111571 TI - Phrenic output changes due to progressive airway denervation in rabbits. AB - The experiments were performed with thirteen anaesthetized rabbits breathing spontaneously through the larynx. Phrenic output was measured during tidal respiration in control conditions and in the course of progressive denervation of the laryngeal and tracheobronchial compartments. We have analysed changes in amplitude and the rate of rise of the integrated phrenic neurogram as well as the changes in TI, TE, TT and f of the respiratory timing after superior laryngeal nerves (SLN-s) section, section of the recurrent laryngeal nerves (RLN-s) and step-wise complete midcervical vagotomy. Nerve sections were performed by two methods: 1) bilateral SLN-s, RLN-s and cervical vagal neurotomy (horizontal method); 2) right-sided neurotomies of SLN, RLN and vagus followed by left-sided neurotomies of these nerves (vertical method). Laryngeal deafferentation did not greatly affect respiratory variables. Unilateral and especially bilateral vocal cord paralysis prolonged the respiratory cycle with enhanced TI/TT ratio, increased amplitude and rate of rise of the integrated phrenic neurogram. Maximum values of all parameters (the rate of rise excluded) were achieved after complete midcervical vagotomy. Of the two methods of denervation, the right-sided followed by left-sided denervation led to better adaptation of the organism to the respiratory disturbance (smaller changes in TI and TE compared with the control values). Denervation by the 'horizontal' method (paired section of the nerves) led to an abrupt failure of effective ventilation. PMID- 3111572 TI - Why add to the confusion? PMID- 3111573 TI - Bacterial antibiotic resistance before and after clinical application in the United States. PMID- 3111574 TI - Antibiotic resistance: a local hospital or community problem. PMID- 3111575 TI - Evidence that the mechanism of the inhibitory action of pinacidil in rat and guinea-pig smooth muscle differs from that of glyceryl trinitrate. AB - The effects of pinacidil have been compared with those of glyceryl trinitrate (GTN) using the aorta and portal vein of the rat and the trachealis and taenia caeci of the guinea-pig. In aorta, both pinacidil and GTN inhibited responses to noradrenaline and showed some selective inhibition of contractions to 20 mM K+. Responses to 80 mM K+ were little affected. In trachealis, both pinacidil and GTN inhibited spontaneous tone and selectively relaxed spasms to 20 mM K+. Responses to 80 mM K+ were unaffected. In portal vein, pinacidil completely inhibited spontaneous electrical and mechanical activity. GTN reduced the amplitude of tension waves and extracellularly-recorded discharges, but increased the frequency of spontaneous electrical and mechanical activity. In portal vein, pinacidil inhibited contractions to noradrenaline and selectively inhibited responses to 20 mM K+. GTN had little inhibitory effect on responses to either noradrenaline or K+. In portal veins loaded with 86Rb as a K+-marker, pinacidil significantly increased the 86Rb efflux rate coefficient whilst GTN had no effect on 86Rb exchange. In taenia caeci, both pinacidil and GTN inhibited the spontaneous tone of the preparation. These inhibitory effects were not antagonized by apamin. It is concluded that pinacidil and GTN do not share a common relaxant mechanism. Evidence has been obtained that pinacidil exerts its inhibitory effects by the opening of apamin-insensitive, 86Rb-permeable K+ channels. PMID- 3111577 TI - Fibrinolysis in systemic lupus erythematosus: effect of desamino D-arginine vasopressin infusion. AB - In systemic lupus erythematosus (SLE) the lupus anticoagulant is known to be associated with thrombosis. However, this anticoagulant only occurs in a small percentage of patients. Histopathological studies suggest a more generalized thrombotic tendency with platelets and fibrin within the microvasculature. Fibrinogen is elevated in SLE and this may lead to the fibrin deposition described. We wondered if decreased fibrinolysis contributed to this and we infused desamino D-arginine vasopressin (DDAVP) into ten patients with SLE and eight controls. DDAVP stimulates endothelial production of plasminogen activator (PA) and factor VIII. Baseline results showed a significant decrease in PA activity with a concomitant increase in fibrinogen in SLE. The t-PA and inhibitor levels were normal but factor VIII was increased. After infusion of DDAVP, results indicated that, despite baseline results, SLE patients were able to respond to stimulation and the increase in PA activity produced a decrease in plasma fibrinogen levels. These findings may have therapeutic implications. PMID- 3111576 TI - Human polymorphonuclear neutrophil activation with arachidonic acid. AB - The capacity of arachidonic acid (AA) to stimulate granule exocytosis from human polymorphonuclear neutrophils (PMNs) was investigated. AA induced the selected extracellular release of azurophil (myeloperoxidase, lysozyme) and specific (lysozyme, vitamin B12 binding protein) granule constituents from human PMNs in a time- and concentration-dependent manner. Cytochalasin B (CB) enhanced but was not required for PMN activation with AA. Although extracellular calcium had no effect on granule exocytosis, AA did stimulate the mobilization of intracellular sequestered Ca2+ which resulted in an increase in cytosolic-free Ca2+ ([Ca2+]i) as reflected by increased fluorescence of Fura-2-treated cells. AA stimulated Ca2+/phospholipid-dependent protein kinase C (PK-C) activity in PMNs. 4,4' Diisothiocyano-2,2'-disulphonic acid stilbene (DIDS), an anion channel blocker, caused a concentration-dependent inhibition of granule enzyme release. Activation of PMNs with AA was unaffected by the lipoxygenase/cycle-oxygenase inhibitors, 5,8,11, 14-eicosatetraynoic acid (ETYA) and benoxaprofen, a lipoxygenase inhibitor, 6, 9, deepoxy-6,9-(phenylimino) delta 6,8-prostaglandin 1(1) (piriprost potassium) or a pure cyclo-oxygenase inhibitor, flurbiprofen. These data define the properties of AA as a secretory stimulus for human PMNs. PMID- 3111579 TI - Food irradiation. PMID- 3111578 TI - Role of urokinase in colorectal neoplasia. AB - The biofunctional activity of the plasminogen activators urokinase and tissue plasminogen activator has been measured in extracts from 50 colorectal carcinomas and 21 adenomas using a bioimmunoassay. Compared with control mucosa urokinase activity was significantly elevated in adenomas (P less than 0.001) and carcinomas, levels being significantly higher in carcinomas (P less than 0.05). In contrast tissue plasminogen activator activity was reduced in adenomas (P less than 0.01) and carcinomas, levels being significantly lower in carcinomas (P less than 0.01). Although enzyme activity did not relate to Dukes' stage or histological grade urokinase activity was higher in carcinomas with venous invasion (n = 17, P less than 0.05), in those with moderate or extensive local spread (n = 27, P less than 0.05) and in cases where a palliative resection only was feasible because of advanced disease (n = 8, P less than 0.05). Urokinase has been implicated in tissue degradation as well as fibrinolysis and may play a role in tumour invasion and metastasis in human colorectal neoplasia. PMID- 3111580 TI - The wasted opportunity of the election. PMID- 3111581 TI - Health and efficiency. PMID- 3111582 TI - The psychological side of tinnitus. PMID- 3111584 TI - Alcohol intemperance and sudden death. AB - Ten years after a health screening examination was offered to 50 year old men 32 of the 2322 participants and 12 of the 454 nonparticipants had died of ischaemic heart disease. Of these, 26 and 11 respectively had suffered sudden death, for which necropsy was performed. Half of the men who had died suddenly had been registered for alcohol intemperance up to 1973, which was four times the prevalence of such registrations in the general population. Registration at both the Swedish Temperance Board and the Bureau of Social Services was associated with an odds ratio of 3.74 for sudden death as compared with not being registered at either. Logistic analysis including the classical risk factors for ischaemic heart disease together with registration for alcohol intemperance and at the Bureau of Social Services showed only the two types of registration and systolic blood pressure to be independent risk factors. On the other hand, there was no overrepresentation of subjects entered in the registers among those surviving a myocardial infarction. For non-fatal myocardial infarction blood pressure and serum triglyceride concentration were significant risk factors and serum cholesterol concentration, smoking, and body mass index probable risk factors; the two types of registration were not independent risk factors. Alcohol intemperance is strongly associated with an increased risk of sudden death after myocardial infarction. PMID- 3111583 TI - Effect of antihypertensive treatment on kidney function in diabetic nephropathy. AB - The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin dependent diabetics (mean age 30). During the mean pretreatment period of 32 (range 23-66) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 72 (range 32-91) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mm Hg to 129/84 mm Hg and albuminuria decreased from 1038 micrograms/min to 504 micrograms/min. The rate of decline in the glomerular filtration rate decreased from 0.89 (range 0.44-1.46) ml/min/month before treatment to 0.22 (range 0.01-0.40) ml/min/month during treatment. The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment (greater than or equal to 6 years). One patient died from acute myocardial infarction (glomerular filtration rate 46 ml/min/1.74 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy. PMID- 3111585 TI - Exertional gastro-oesophageal reflux: a mechanism for symptoms in patients with angina pectoris and normal coronary angiograms. AB - During 24 hour oesophageal pH monitoring 52 patients who had angina pectoris and normal coronary angiograms underwent exercise testing, as far as their symptoms allowed, on a treadmill to determine whether gastro-oesophageal reflux occurred during exertion. In 11 patients the 24 hour oesophageal pH score was abnormally high; 10 of these showed exertional gastro-oesophageal reflux, and in nine this was associated with their usual chest pain. A further 13 patients had a normal 24 hour pH score but had exertional reflux coincident with chest pain during exercise testing. The mean lower oesophageal sphincter pressure in both of these groups of patients was appreciably lower than that in 28 patients who had a normal 24 hour pH score and no exertional reflux. These findings suggest that exertional gastro-oesophageal reflux accounts for the symptoms of a large proportion of patients who have angina pectoris and normal coronary angiograms and that oesophageal pH monitoring during exercise testing on a treadmill enables this group of patients to be identified. PMID- 3111586 TI - Metabolic alkalosis and hyperlactataemia. PMID- 3111587 TI - Are routine bacteriological cultures necessary in an accident and emergency department? PMID- 3111588 TI - Herpes zoster of second and third segments causing ipsilateral Horner's syndrome. PMID- 3111589 TI - Balloon occlusion of pharyngeal pouch as aid to nasoenteric intubation. PMID- 3111590 TI - Appointment systems: feasibility study of a new approach. AB - Patients in a semirural dispensing practice were asked to determine how much time they required when booking an appointment. A comparison was made between their estimates and the actual time taken. Patients' estimates proved sufficiently accurate to produce a system that worked well. PMID- 3111591 TI - Prediction of resources needed to achieve the national target for treatment of renal failure. AB - A model of the treatment of end stage renal failure has been primed with observed survival statistics and used to predict the steady state that will be achieved when the present annual target of at least 40 new patients per million population is in equilibrium with the death rate. The number of patients expected to receive each type of dialysis or a transplant is given per million of population. The personnel and facilities required to care for these patients and the costs of each programme were derived using analyses of workloads and costs in the North Western Regional Health Authority. The study has documented the considerable need for "back up" beds for patients on dialysis who require temporary care as inpatients. The cost effectiveness of transplantation has been demonstrated; at steady state it is calculated that each successful graft saves the service pounds 30,000. Implementation of the minister's minimum target requires a build up to some three times the resources currently allocated, with parallel increases in numbers of medical, nursing, and other essential staff. PMID- 3111592 TI - What is a good consultant? View from New Zealand. PMID- 3111593 TI - Compartment syndromes in unconscious patients: a simple aid to diagnosis. PMID- 3111595 TI - Coping with sudden death. PMID- 3111594 TI - ABC of AIDS. Gastrointestinal and hepatic manifestations. PMID- 3111597 TI - Mortality from myocardial infarction in different types of hospitals. PMID- 3111596 TI - Housing conditions and ill health. PMID- 3111598 TI - Internal market in the NHS. PMID- 3111599 TI - Bone mineral density in Addison's disease. PMID- 3111600 TI - Treating Paget's disease. PMID- 3111601 TI - HIV testing and differential diagnosis. PMID- 3111602 TI - AIDS: when to test. PMID- 3111603 TI - Clinical algorithms: irregular vaginal bleeding. PMID- 3111604 TI - Simple thyroid cyst: cause of acute bilateral recurrent laryngeal nerve palsy. PMID- 3111606 TI - Drug formularies in hospitals. PMID- 3111605 TI - Look after your heart. PMID- 3111607 TI - Evaluating mass training in cardiopulmonary resuscitation. PMID- 3111608 TI - Lower oesophageal contractility as an indicator of brain death in paralysed and mechanically ventilated patients with head injury. PMID- 3111609 TI - Doctors in management: three doctors' experiences. PMID- 3111610 TI - Extracranial-intracranial bypass, one; clinical trials, nil. PMID- 3111611 TI - The future role of midwives. PMID- 3111612 TI - Not all travellers need immunoglobulin for hepatitis A. PMID- 3111613 TI - The cost of unnecessary tests by day or night. PMID- 3111614 TI - Vasomotor rhinitis. PMID- 3111615 TI - Prevention of recurrent acute cystitis by methenamine hippurate: double blind controlled crossover long term study. AB - In a randomised, double blind, long term, crossover study 1 g twice daily of methenamine hippurate was compared with placebo for its preventive effect on recurrent attacks of acute cystitis. Methenamine hippurate and placebo were interchanged every six months for two years. During one of the years patients took 250 ml extra fluid every morning and evening. Out of 21 enrolled patients, 14 completed the first year and 13 both years of treatment, which permitted the evaluation of 27 patient years. There were 52 episodes of acute cystitis caused by reinfection: 41 occurred during placebo treatment and only 11 during the methenamine hippurate regimen (p less than 0.01). Extra fluid intake did not reduce the incidence of acute cystitis, nor did it reduce the effect of methenamine hippurate. Methenamine hippurate is an effective prophylactic agent against recurrent acute cystitis and has the advantage of not inducing cross resistance to conventional antibiotics. PMID- 3111616 TI - Influence of non-steroidal anti-inflammatory drugs on the outcome of faecal occult blood tests in screening for colorectal cancer. AB - Non-steroidal anti-inflammatory drugs have been accused of causing false positive results in faecal occult blood tests for colorectal cancer. A study was therefore performed in 10,931 people undergoing faecal occult blood screening tests to assess the effect of these drugs on the predictive value of a positive test result. Those with a positive result were interviewed and a full drug history was taken before they underwent a full colorectal examination. Of the 455 people with a positive result, 50 were taking non-steroidal anti-inflammatory drugs: 10 (20%) had colonic neoplasia. Of the 405 who were not taking non-steroidal anti inflammatory drugs, 129 (32%) had colonic neoplasia. These detection rates were not significantly different, and the predictive value of a positive result for an adenoma larger than 1 cm was 14% in the group not taking anti-inflammatory drugs and 26% in the group taking them (not significant). These results suggest that a finding of occult faecal blood cannot be attributed to upper gastrointestinal tract bleeding caused by non-steroidal anti-inflammatory drugs and should be followed by a thorough colorectal examination. PMID- 3111617 TI - Psychosocial effects of radiotherapy after mastectomy. AB - Psychosocial morbidity was measured in 47 patients who received postoperative radiotherapy and in 38 who received no further treatment after mastectomy. Roughly one third of all patients experienced depression or anxiety. One month after operation, before radiotherapy, there were no significant differences between the two groups in any of the measures of psychosocial morbidity. Knowledge of impending treatment did not seem to influence morbidity. At three months patients who had completed radiotherapy had significantly more somatic symptoms and social dysfunction than those not so treated. At six months the radiotherapy group continued to show more somatic symptoms, but a year after operation there were no significant differences between the groups. Although several patients who received radiotherapy were upset by their treatment, the study failed to confirm that depression and anxiety were commoner among those given radiotherapy than among patients given no further treatment. PMID- 3111618 TI - Ovarian neoplasms, functional ovarian cysts, and oral contraceptives. AB - The incidence of ovarian neoplasms and functional ovarian cysts diagnosed at laparotomy or laparoscopy among the 17,000 women taking part in the Oxford Family Planning Association contraceptive study was investigated. Epithelial cancer of the ovary was only 25% as common among those who had ever taken oral contraceptives as those who had never done so (95% confidence interval 8% to 67%). There was little evidence of any important association between use of oral contraceptives and benign teratoma or cystadenoma. Functional cysts of the ovary occurred much less commonly in women who had recently (in the six months preceding diagnosis) taken combined oral contraceptives (but not in those who had taken progestogen only oral contraceptives) than in those who had never taken oral contraceptives or had taken them in the past. This protective effect was more pronounced for corpus luteum cysts (78% reduction; 95% confidence interval 47% to 93%) than for follicular cysts (49% reduction; 95% confidence interval 20% to 70%). It is estimated that about 28 (95% confidence interval 16 to 35) operations for functional ovarian cysts are avoided among every 100,000 women who take oral contraceptives each year. PMID- 3111619 TI - Hypogonadism induced by luteinising hormone releasing hormone agonist analogues: effects on bone density in premenopausal women. PMID- 3111620 TI - Pyomyositis associated with human immunodeficiency virus infection. PMID- 3111621 TI - Myocardial infarction due to amphetamine. PMID- 3111622 TI - Life threatening haemorrhage from a mycotic renal pseudoaneurysm treated by segmental renal artery embolisation. PMID- 3111623 TI - Measles: who pays the cost? AB - An epidemic of measles resulting in 164 cases in a Leicester group practice was analysed by means of a case-control study and a questionnaire. Estimates were made of the physical, social, and financial costs to children, parents, and family doctors. On average each child was ill for 10.8 days and the illness cost his parents pounds 11.06. His family doctor spent 26 minutes providing care. These results provide an additional stimulus to the primary care team to promote the uptake of measles vaccination. PMID- 3111624 TI - Medical malpractice in perspective. I--The American experience. AB - Concern over the possibility of an American style medical malpractice "crisis" in the United Kingdom has recently been voiced by members of both medical and legal professions. The validity of such fears is examined by reviewing the conditions that have given rise to the current American difficulties. It is argued that the rise in malpractice insurance premiums and associated restrictions in availability should be seen against the background of underwriting problems specific to medical liability in conjunction with a general decline in reinsurance cover. The evidence in relation to the clinical and resource implications of malpractice is analysed. In particular, arguments that increased litigation has influenced the practice of "defensive" medicine and the choice of specialty are critically examined. Medical malpractice claims and insurance are only part of a professional environment which is undergoing dramatic social and economic changes, many of which seem more plausible candidates to be treated as important influences on the nature and organisation of health care in the United States. PMID- 3111626 TI - Getting the message across. PMID- 3111625 TI - Portraits from memory. 15--Professor James Walter McLeod, OBE, FRS (1887-1978). PMID- 3111627 TI - What is a good consultant? The ideal from a manager's point of view. PMID- 3111628 TI - Early onset pre-eclampsia: recognition of underlying renal disease. PMID- 3111629 TI - Hospices for children? PMID- 3111630 TI - Clinical algorithms: infertility. PMID- 3111631 TI - Unemployment and mortality. PMID- 3111632 TI - What are health authorities doing about the health problems caused by unemployment. PMID- 3111633 TI - Subcutaneous calcium heparin versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs. PMID- 3111634 TI - Medical staffing and training in the West Midlands region. PMID- 3111635 TI - Inequalities in health: changes in RHAs in the past decade. PMID- 3111636 TI - Buffers and H2O2 reduce neuronal death and/or enhance differentiation of neurons and astrocytes in dissociated mouse brain cultures. AB - Tissue of the mammalian central nervous system (CNS) undergoes complex and uncoordinated pathological responses upon injury. Efforts to develop pharmacological approaches to achieve functionally meaningful regeneration largely have been unsuccessful. Assuming that anoxia and drop in tissue H are initiating factors in most pathological sequences consequent to CNS injury, we studied the effects of increasing the buffering and oxygenating capacities of the medium on dissociated embryo brain cultures. The presence of H2O2 in the medium led to greatly enhanced neuronal survival and/or differentiation. Increased buffering capacity favored enhanced neurite outgrowth with remarkable elongation of fibers. A combination of the two gave a synergistic effect in which both of the above responses were seen. Both buffers and H2O2 enhanced astrocytic differentiation and extension of processes while reducing DNA synthesis. The results favor the view that attempts to encourage self-repair in CNS tissue or to enhance repair of CNS damage with potential therapeutic agents or procedures should be carried out in the context of a near optimal environment in which, at the least, pH and pO2 values are stably maintained within normal operational limits. PMID- 3111637 TI - Carbon dioxide reactivity of cerebral cortical and pial arteries in spontaneously hypertensive and normotensive rats--a morphometric study. AB - The responsiveness of cerebral arteries to the changes in arterial carbon dioxide tension (paCO2) was studied in spontaneously hypertensive rats (SHRs) and normotensive rats (NTRs). A freeze substitution method was applied for the preparation of pial and cortical arteries for morphometrical study. Hypercapnia was induced by giving 8% CO2, and hypocapnia was provided by hyperventilation. The ratios of internal (d) to external diameter (D) (d/D ratio) of both pial and cortical arteries in SHR were not different from those in NTRs during normocapnia. In hypercapnia, the ratios of pial and larger cortical arteries (D greater than or equal to 20 micron) in SHRs were 80.9 +/- 0.8% and 78.6 +/- 0.6%, respectively, being significantly smaller than 86.2 +/- 0.7% and 82.2 +/- 0.5% in NTR. In contrast, the d/D ratio of pial arteries in hypocapnia was 72.5 +/- 1.4% in SHRs, which was significantly larger than 67.5 +/- 1.4% in NTRs. The responsiveness of smaller cortical arteries (D less than 20 micron) to paCO2 was not different between SHRs and NTRs. The present results suggest that in SHRs cerebrovascular CO2 reactivity is decreased as compared to NTRs, especially in pial and larger cortical arteries. PMID- 3111638 TI - Neurotoxicity of adriamycin passed through the transiently disrupted blood-brain barrier by mannitol in the rat brain. AB - Neurotoxicity of adriamycin (ADM) was investigated following the transient disruption of the blood-brain barrier (BBB) in rats. The BBB disruption by the hyperosmotic agent (1.4 M mannitol) was confirmed by the leakage of ADM and Evans blue administered intravenously. Neuropathological changes due to the toxicity of ADM were found as early as day 4. The neurons in the cerebral cortex and nucleus caudatus-putamen showed focal clearing of the nuclear chromatin, increased dense bodies in the cytoplasm and dilatation of the cisternae of the rough endoplasmic reticulum (r-ER) and Golgi apparatus. By day 7, nucleolar segregation and irregular membranous structures appeared in the nuclei with the progression of cytoplasmic changes. By day 10, the cytoplasm of many neurons was vacuolated. Electron-microscopically, the cisternae of the r-ER and Golgi apparatus were prominently dilated in these neurons. Neuronal microtubules were increased in number, in particular in the perinuclear region. Numerous whorl-like membranous structures and separation of nuclear membrane were also observed. Some astrocytic processes surrounding the blood vessels revealed loss of organelles and a few pericytes showed an increased number of lysosomes on days 7 and 10. This experiment clearly demonstrates that ADM has strong neurotoxic effects in the central nervous system when the BBB is disrupted, and provides the warning for the possibilities of neurotoxic side effects when ADM is administered, in combination with a hyperosmotic agent, for the treatment of human malignant tumors, including brain tumors. PMID- 3111640 TI - The release of octopamine and proctolin from an insect visceral muscle: effects of high-potassium saline and neural stimulation. AB - The release of octopamine and proctolin from the oviduct visceral muscles of the locust, Locusta migratoria, has been investigated. Salines containing elevated potassium concentrations (100 mM) were capable of releasing both octopamine and proctolin, although the proportion of the total store of octopamine released (19%) was much greater than that of proctolin (0.4%). The high potassium-induced release of octopamine was calcium-dependent. Electrical stimulation of the oviducal nerves also resulted in the release of octopamine and proctolin. The release of both substances was frequency-dependent with maximum release of octopamine occurring at about 5 Hz, and maximum release of proctolin at 30 Hz. Neural stimulation was a more effective means of inducing proctolin release than was high-potassium saline, with 6.3% of the total store of proctolin released with 5 min stimulation at 30 Hz. The neurally stimulated release of proctolin was calcium-dependent. In addition, intrasomatic stimulation of the octopaminergic neurons which project to the oviducts resulted in the release of octopamine. The results clearly indicate that both octopamine and proctolin, which have previously been shown to be associated with locust oviducts, are released in a calcium-dependent manner by physiological stimuli. This strengthens the case for octopamine and proctolin as natural regulators of this insect visceral muscle. PMID- 3111639 TI - Single olfactory organ associated with prosencephalic malformation and cyclopia in a Xenopus laevis tadpole. AB - A cyclops Xenopus laevis tadpole with a single olfactory organ is described. At a stage comparable to 48, the telencephalon was severely atrophic and only the region where the olfactory fibres terminated appeared to have the cytoarchitecture of the olfactory bulb. In this animal the central nervous system (CNS) appeared normally developed only posterior to the preoptic area. The hypothesis of a diencephalic origin of the region where the olfactory fibres terminated is discussed in the light of our previous results of olfactory placode transplantation. By analogy between this case and other malformations (cyclopia, holoprosencephaly) in higher vertebrates and humans, the need is emphasized for a more precise anatomical description of the olfactory input in related malformations. PMID- 3111641 TI - Characterization of the analgesic effects of the benzodiazepine antagonist, Ro 15 1788. AB - Three experiments were carried out in rats to evaluate the analgesic effects of the benzodiazepine antagonist, Ro 15-1788. Expt. 1 demonstrated a diazepam reversible analgesic effect of Ro 15-1788 using the tail-flick test. Expt. 2 analyzed the effects of Ro 15-1788 in the hot-plate test at various doses. Low doses of Ro 15-1788 proved analgesia 20 min after drug injection, whereas high doses had no analgesic effect on the 20 min test, but were effective on the 50 min test. Expt. 3 demonstrated that the opiate antagonist, naloxone, had no effect on analgesia produced by Ro 15-1788 in the hot-plate test. The analgesic effects of Ro 15-1788 may be attributable to its reported anxiogenic properties. PMID- 3111643 TI - Lesion size and recovery of function: some new perspectives. AB - The present article discusses the possibility that functional recovery following brain damage may be to a large degree dependent on the amount of nervous tissue destroyed, such that more neuronal destruction may lead to more and not (as commonly suggested) to less recovery. This assumption may derive from the neuropsychological and neurological literature: many cases with circumscribed brain lesions are implicated with severe functional losses. However, patients with dramatic and severe brain destructions often show astonishingly normal behavior regarding cognition, speech, visuospatial, motor and sensory functions. Animal experimentation as well shows that an extensive lesion of a brain area may be associated with equal or less functional detriment than a small lesion of the same area. Along with the well-known variables of age, lesion growth, or personality and environmental factors, the amount of tissue destroyed should be considered as a potent mediator of functional recovery. At least for some functions and brain regions, the likeliness of recovery may increase with the extent of the lesion and thus the necessity of the brain to fulfill plastic changes. PMID- 3111642 TI - Analgesic effects of the progesterone metabolite, 3 alpha-hydroxy-5 alpha-pregnan 20-one, and possible modes of action in mice. AB - The effects of intracerebroventricular (i.c.v.) administrations of the progesterone metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3A5P), on the nociceptive responses of male mice were examined. 3A5P elicited significant, dose dependent (0.001-1.0 microgram) analgesia for 90-120 min after administration. These effects of 3A5P were significantly more potent than those of progesterone. The stereoisomer, 3 beta-hydroxy-5 alpha-pregnan-20 one (3B5P), failed to affect the nociceptive responses, indicating that the analgesic effect of 3A5P is stereospecific. The analgesic effects of 3A5P were blocked by peripheral administrations of the GABA antagonists, bicuculline and picrotoxin, and reduced by both the opiate and benzodiazepine antagonists, naloxone and Ro 15-788, respectively. The calcium channel antagonists, nifedipine and verapamil, enhanced 3A5P-induced analgesia but had no evident effects on the actions of 3B5P. These results suggest that the central analgesic effects of the progesterone metabolite, 3A5P, may arise via mechanisms involving calcium channels, the GABA benzodiazepine-chloride complex and endogenous opioid systems. PMID- 3111644 TI - Effects of antimitotic drugs on the morphological features of PC12 cells in culture--a light and EM study. AB - PC12 cells were grown in monolayer cultures either as untreated controls or treated with (1) NGF, (2) mitomycin C/BUdR, or (3) a combination of NGF and mitomycin C/BUdR. The cells from these four groups were processed for scanning and transmission electron microscopy and for fluorescence histochemistry. With scanning electron microscopy, the control and mitomycin C/BUdR treated cells showed the presence of very small extensions for attachment, and numerous fine processes on the cell surface, while the NGF treated cells and cells treated with the combination exhibited many large processes that were even longer with the combination treatment. The combination treatment also inhibited cell growth completely. Fluorescence histochemical studies revealed strong fluorescence in the perikarya of cells from all the four groups. Transmission electron microscopic studies showed that the cells in all the four groups contained many chromaffin-type granules in addition to the presence of other cellular organelles. The neurites in the NGF group and the combination treatment also contained these granules and well-defined microtubules. Therefore, antimitotic agents inhibit PC12 cell growth without affecting important cellular parameters. PMID- 3111645 TI - Effects of protein concentration on responses to dietary lysine by chicks. AB - Chicks were fed on diets varying in crude protein (CP) content (140 to 280 g/kg diet) in either 8 steps, experiment 1, or 6 steps, experiment 2. Protein composition was held constant in each experiment. At each protein concentration, 5 (experiment 1) or 6 (experiment 2) concentrations of lysine were tested, ranging from 40 to 60 g/kg CP. Growth rate and efficiency of food utilisation to 21 d of age responded to increasing dietary protein contents up to about 230 g CP/kg. An estimate of lysine requirement at each protein concentration was obtained by fitting a quadratic curve to the response data and calculating the dose of lysine (g/kg CP) needed to maximise either growth rate or gain/food ratio. Although no growth response to dietary protein was obtained between 240 and 280 g CP/kg, the amount of lysine needed to maximise growth and gain/food ratio over this range increased systematically when expressed as g/kg diet, but remained constant if expressed as g/kg CP. The regression of lysine required (g/kg diet) for maximum performance (growth or food efficiency) on CP (g/kg diet) was strictly linear for both responses in both experiments throughout the entire range studied (140 g CP/kg to 280 g CP/kg). The estimated lysine requirement was 0.053 of the CP in experiment 1 and 0.055 of the CP in experiment 2. It is concluded that a fixed ratio of lysine to protein should be specified in practical diet formulation, rather than a minimum dietary concentration of lysine. This would ensure that, if the dietary protein content rises above a prescribed minimum value in least-cost formulation, an appropriate adjustment will automatically be made to the lysine content of the solution. PMID- 3111646 TI - Combined use of topical cyclosporin A and silver sulphadiazine on allografts infected with Pseudomonas in burned rats. AB - In this study, we investigated the effects of a combination of topical Cyclosporin A (CyA) and silver sulphadiazine on infected and normal skin allografts in burned and unburned rats. Buffalo (Buf) allografts on unburned Lewis (Lew) recipients survived 16.8 +/- 0.9 days after a 10-day course of topical CyA and silver sulphadiazine, as compared to 7.4 +/- 1.1 days for untreated allografts and 18.6 +/- 0.9 days for those receiving CyA only for 10 days. Allografts infected with Pseudomonas aeruginosa and placed on burned recipients survived significantly longer (13.7 +/- 1.1 days) when treated with silver sulphadiazine and topical CyA for 7 days compared to a similar group of animals treated with silver sulphadiazine alone (8.4 +/- 1.0 days). The mortality rate for burned, infected and allografted animals receiving no medication or topical CyA was 50 per cent compared with zero in animals treated with silver sulphadiazine only or combined silver sulphadiazine and topical CyA. PMID- 3111647 TI - [Demonstration of Langerhans cells in the human bronchial epithelium]. AB - Ultrastructural and immunohistochemical analysis of six specimens revealed for the first time a small number of Langerhans cells in non-neoplastic bronchial epithelium. These cells were usually found either interspersed perpendicularly between columnar epithelial cells or just above the basal lamina with extending cytoplasmic processes. Usually few Birbeck granules, especially located in the Golgi region, were present throughout the cytoplasm. Immunohistochemical studies were performed on semi-thin sections with a polyclonal anti-S-100 protein. The population of S-100 positive cells represented about 1% of all the epithelial cells. Not all ultrastructurally identified Langerhans cells were shown to be positive for S-100 antigen. Our results suggest that Langerhans cells could be a constant cellular constituent for the normal bronchial epithelium. The exact function of Langerhans cells in the respiratory epithelium remains to be investigated, but they may have an immunologic function, such as antigen presentation to T lymphocytes. PMID- 3111648 TI - [Artificial nutrition and acute pancreatitis. Recent data]. PMID- 3111649 TI - [Comparison of fentanyl and alfentanil in ambulatory anesthesia]. PMID- 3111650 TI - Imaging primary lung cancers, pleural cancers, and metastatic disease. AB - Evaluation of primary lung cancers, pleural cancers, and metastases should be based on the TNM system. The optimal selection of imaging modalities can be difficult, and there is no universal agreement on the approach to the workup. Diagnostic pathways can provide guidelines for radiologic imaging sequencing based on the TNM system (Figs. 21-23). No algorithm, however, can fit all situations, and each cancer may require a distinct approach. PMID- 3111651 TI - Imaging tumors of the central nervous system and extracranial head and neck. AB - Both CT and MRI address the pertinent clinical issues in the management of patients with squamous cell carcinoma of the upper aerodigestive tract and neck, and are crucial to staging, treatment, and follow-up. By combining the clinical assessment of primary mucosal extent with the objective information provided by CT or MRI about deep tissue extension of the primary tumor and any nodal metastases, accurate assessment of the actual pretreatment primary tumor and nodal stages is possible. With this objective picture of tumor extent, decisions about surgery and radiotherapy can be made for primary and recurrent tumors, as well as for nodal metastases. PMID- 3111652 TI - Imaging in bone cancer. PMID- 3111653 TI - Carcinoma of the male breast and Klinefelter's syndrome: is there an association? AB - There appear to be no substantial data to confirm the assumption that breast cancer in men with Klinefelter's syndrome is as common as breast cancer in the normal female population. The number of reported cases of breast cancer in Klinefelter's males is only 27, a number too small for any meaningful statistical analysis. There is evidence, however, to suggest that Klinefelter's males have an increased risk of breast cancer that approaches three percent. Physicians should therefore be aware of potential breast pathology in XXY males and incorporate a careful breast examination and specific education into the routine health maintenance of men with Klinefelter's syndrome. PMID- 3111654 TI - Ovarian cancer. PMID- 3111655 TI - The ethical dilemma of phase I clinical trials. PMID- 3111656 TI - [Treatment of 50 cases of liver cancer by hepatic artery embolism]. PMID- 3111657 TI - [Evaluation of serum glycylproline dipeptidyl aminopeptidase activity in the diagnosis of primary liver cancer]. PMID- 3111658 TI - [Combined use of artemether with other antimalarials in the treatment of falciparum malaria]. PMID- 3111659 TI - [Characteristics of exercise load and pulmonary ventilation in normal people at high altitudes]. PMID- 3111660 TI - [Preparation and clinical application of HLA-B27 antisera]. PMID- 3111662 TI - [Value of the determination of serum catecholamine metabolites in the early diagnosis of neuroblastoma]. PMID- 3111663 TI - [Experimental study on artificial infection of alveolar hydatid in gerbils]. PMID- 3111661 TI - [Whole-body protein turnover and plasma glycine kinetics in chronic renal failure before and after treatment with essential amino acids]. PMID- 3111664 TI - [Uses of abdominal B-mode ultrasonic equipment in craniocerebral operations]. PMID- 3111666 TI - Self-care models for long term care. PMID- 3111665 TI - [The status of computer-aided diagnosis in China]. PMID- 3111667 TI - Effects of long-term maintenance therapy with a new glucocorticoid, deflazacort, on mineral metabolism and statural growth. AB - Deflazacort was substituted for Prednisone (based on the equivalence 1 mg Prednisone equals 1.2 mg Deflazacort), during maintenance glucocorticoid therapy in 9 children, 5 with renal diseases and 4 with connective tissue or immunoproliferative disorders. Six patients received 0.26-0.35 mg/kg body weight (B.W.)/day and 3 0.48-1.2 mg/kg B.W. on alternate days, for 10-16 months. Except for a child with chronic juvenile arthritis, who was also unresponsive to Prednisone, the therapeutic effects of Deflazacort were excellent. Steroid side effects present in 8 patients decreased or disappeared. Plasma Ca, P, Mg, creatinine, alkaline phosphatase, iPTH(1-34), urinary excretion of Ca, cAMP, and TRP remained normal. Plasma iPTH(1-84) remained normal in 5 children; in the other 4 patients it increased from normal to slightly elevated values. On Deflazacort, plasma calcidiol concentrations were within the normal range in 6/8 patients prescribed daily doses of vitamin D2 (1,600-2,400 IU) or calcidiol (20 micrograms). Plasma 1,25(OH)2D levels monitored in 5 children were also normal. The osteoporosis, evaluated on the tibial cortico-diaphyseal ratio and the trabecular aspect of bone radiograms, present in 5 patients, persisted in 1 and improved in the others. On Deflazacort, statural growth proceeded normally in all subjects, with a modest acceleration of growth velocity in 3 children. These results seem encouraging for extending clinical trials with Deflazacort to the active phase of pediatric diseases requiring glucocorticoid. PMID- 3111668 TI - Bone density of the radius, spine, and hip in relation to percent of ideal body weight in postmenopausal women. AB - Bone mineral content (BMC) and bone mineral density (BMD) of the spine (L2-L4) and hip (at femoral neck, Ward's triangle, and greater trochanter sites) were determined by dual-photon absorptiometry (DPA), and of the radius by single photon absorptiometry (SPA) in healthy postmenopausal women aged 40-70 years. The relationships of BMC and BMD to years since menopause were examined separately in 97 women who were above 115% of ideal body weight (IBW) and in 128 women below. The heavier women had significantly greater mean BMC and BMD at each site than did the normal-weight women. In the normal-weight women, there was a significant negative correlation between BMD and years since menopause at each measurement site except the greater trochanter. In the obese women, BMD decreased with increasing years since menopause at the radius site only and BMC declined with increasing years after menopause at the hip (femoral neck and Ward's triangle region) as well as the radius. Thus, body size is a significant determinant of BMD in this population. The pattern of loss of BMD from Ward's triangle and femoral neck regions of hip are similar to that of the spine. The BMC and BMD findings in the hip suggest that remodeling occurs at this weight-bearing site which has a favorable effect on bone strength. PMID- 3111670 TI - Compressive strength, ash weight, and volume of vertebral trabecular bone in experimental fluorosis in pigs. AB - The aim of the investigation was to measure the effect of fluoride on vertebral trabecular bone compressive strength and to correlate this with fluoride-induced changes in bone density. This correlation would express changes in the quality of bone during fluoride treatment. Pigs were used in the experiment because their trabecular bone structure and remodeling sequences are very similar to the human. Eight animals receiving a supplement of 2 mg F-/kg b.w. per day from age 8-14 months were compared with 8 control animals. Morphologic measurements in the animals receiving fluoride supplement showed a significant increase of 17% in bone density and a smaller, insignificant increase of 3% in ash weight analyses. Meanwhile, the mechanical parameters for the fluorotic animals were unchanged (maximum compressive strength, maximum stiffness, and energy-absorption capacity) or decreased (normalized compressive strength = maximum compressive load corrected for ash density). It is concluded that the increased bone mass during the initial stages of fluoride treatment does not necessarily indicate an improved bone quality. The discrepancy between bone mass and strength could be either a permanent or a temporary phenomenon and requires further investigation. PMID- 3111672 TI - Neuronal growth factors from tumours of Von Recklinghausen neurofibromatosis. AB - Explants of 21 neurofibromas from 16 patients with Von Recklinghausen neurofibromatosis (NF-I) plus tumour tissue from 5 comparison patients and normal tissue from one of the NF-I patients were assayed for neuronal growth factor(s) using dissociated embryonic sensory neurons from chick embryo. Twenty-one of 21 neurofibroma explants released detectable quantities of neuronal growth factors, but only 2 of 8 non-neurofibroma tissue explants released activity. While antiserum to mouse nerve growth factor (NGF) fractionally inhibited neurite outgrowth induced by some of the neurofibromas, overall differences between assays containing antibody and controls reached statistical significance in 3 cases; in one case, explants of a separate tumour from the same patient had no detectable NGF-like activity. These data support the hypothesis that local release of neuronal growth factors in neurofibromas are responsible for neurites observed within these tumours. Further evidence that endoneurial tissue of peripheral nerve is a rich source of heterogeneous neuronal growth facts has been provided by these studies. PMID- 3111671 TI - Immunocytochemical localization of gamma-carboxyglutamic acid-containing proteins (osteocalcin) in rat bone and dentin. AB - Gla-protein or osteocalcin is one of the most abundant noncollagenous matrix proteins found in bone and dentin. The present study describes, with high resolution, the intracellular and extracellular distribution of Gla-protein in alveolar bone and incisor dentin. Sections of tissues embedded in Lowicryl K4M were incubated with rabbit antibodies to rat dentin Gla-protein. The site of the specific antigen-antibody reaction was revealed by the protein A-gold complex. Labeling was detected over bone and dentin while fewer gold particles were present over prebone and predentin. Gold particles were also seen over the protein synthetic organelles (rough endoplasmic reticulum, Golgi apparatus) of osteoblasts and odontoblasts. These findings confirm, with improved resolution, previous light immunohistochemical studies, and offer the possibility to examine the secretory pathway of the protein. PMID- 3111669 TI - The effect of fluoride and calcium on spinal bone mineral content: a controlled, prospective (3 years) study. AB - Daily treatment with 30 mg of sodium fluoride (NaF) and 1 g of calcium over a 3 year period increased the bone mineral content (BMC) in the spines of women (n = 25) with osteoporosis. Determination of the BMC was followed with dual photon absorptiometry (137Cs-241Am) in the third lumbar vertebra. No increase in BMC was found with only 10 mg sodium fluoride in combination with calcium (n = 25), with calcium alone (n = 25), or with placebo (n = 25). No serious side effects were registered. There was, however, minor gastrointestinal distress in one-fifth of the patients taking 30 mg NaF daily. PMID- 3111673 TI - Indomethacin is effective against neurogenic hyperthermia following cranial trauma or brain surgery. AB - The effectiveness of indomethacin treatment (1 mg/kg) as an antipyretic was tested in patients after cranial trauma or brain surgery involving the centromedial forebrain. Indomethacin was effective in reducing temperature in 10 of 11 cases which showed a dipyrone-resistant hyperthermia developing in the first 24 hours after brain damage, while no significant antipyretic effect was seen in hyperthermic cases developing more than 72 hours after cranial trauma or brain surgery. Biochemical tests estimating the effect of indomethacin, and pyrazolone derivatives on the arachidonic acid metabolism showed significant effects of indomethacin only in influencing cyclooxygenase activity and no effect of any drugs on lipoxygenase actions. In view of these observations, the use of indomethacin is recommended as a treatment for neurogenic hyperthermia. PMID- 3111676 TI - Lithium and memory: a review. AB - This paper reviews systematic clinical studies suggesting memory and cognitive impairment in patients suffering from unipolar and bipolar affective disorders treated with lithium. A number of studies failed, however, to demonstrate lithium induced memory deficits. Thus, the results of studies were equivocal. This lack of empirical consensus was in part due to the heterogeneity of samples and a variety of methodological and design problems. The definition of short- and long term memory was often arbitrary and lacked standard criteria. Some studies revealed a stability of the memory test scores over time and showed that subjective complaints of memory impairment were correlated with depression. The authors also reviewed studies examining the effects of lithium on cognition and memory of healthy control subjects. In animal research it was difficult at times to distinguish between toxic and pharmacologic effects of lithium. There is a need for prospective studies of the effect of lithium in large samples of patients using refined memory tests. PMID- 3111675 TI - Effects of saffan on cardiopulmonary function in healthy cats. AB - The effects of saffan on cardiopulmonary function were evaluated in eight healthy adult cats. Measured values were cardiac output by thermodilution, heart rate by electrocardiogram, arterial blood gases, respiratory rate and systolic, diastolic and mean arterial blood pressures by arterial catheterization. Calculated values included cardiac index, stroke volume and systemic vascular resistance. Statistical analysis employed paired t-tests comparing pre saffan anesthetic induction and post saffan anesthetic parameters over a 120 minute time sequence. Thirty min after saffan induction, significant depression in cardiac output was evident while stroke volume was significantly depressed at 45 and 60 min, systolic blood pressure at 15 min and respiratory rate at 5, 10 and 15 min. No significant changes occurred in cardiac index, heart rate, arterial blood gases, diastolic and mean arterial blood pressure or systemic vascular resistance. It was concluded that saffan causes significant depression of cardiopulmonary function in normal adult cats. PMID- 3111674 TI - The effects of desmopressin on plasma factor VIII/von Willebrand factor activity in dogs with von Willebrand's disease. AB - Eight unanesthetized normal dogs and seven dogs with von Willebrand's disease (vWD) were given desmopressin (0.6 micrograms/kg, IV) in order to determine the effects of this drug on plasma Factor VIII/vWF activity. Seven of the normal dogs and four of the vWD dogs were administered an equal volume of saline (control infusion) on another occasion. The other three vWD dogs underwent major surgery after treatment with desmopressin. Plasma FVIII coagulant activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), and FVIII-ristocetin co-factor activity (FVIII:RC) were quantitated before infusion and at 60 minutes postinfusion. Activities were expressed as a percentage of the activity of a pooled canine plasma (12 dogs) arbitrarily designated as having 100% FVIII:C, vWF:Ag, and FVIII:RC activity. Plasma FVIII:C activity increased by 28% in the normal dogs and by 37% in the dogs with vWD. Plasma vWF:Ag increased more than twofold in normal dogs after desmopressin treatment. In the vWD dogs the average increase was also twofold, however there was much greater variability between dogs with increases ranging from 1.2 fold to 2.4 fold. Plasma FVIII:RC activity almost doubled in normal dogs, however like vWF:Ag, the increases in vWD dogs were more variable. One vWD dog had no increase in FVIII:RC while in the remaining six dogs FVIII:RC increases ranged from 1.8 to 2.9 fold. The results of this study indicate that a single intravenous dose of desmopressin (0.6 micrograms/kg) causes a significant elevation in plasma vWF:Ag and FVIII:RC activity and a much lesser increase in FVIII:C activity in normal unanesthetized dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111677 TI - Phase II study of recombinant human interferon gamma (S-6810) on renal cell carcinoma. Summary of two collaborative studies. Recombinant Human Interferon Gamma (S-6810) Research Group on Renal Cell Carcinoma. AB - Seventeen institutions in Japan evaluated the antitumor activity of recombinant human interferon gamma (S-6810) as a new modality for advanced renal cell carcinoma. The response rate for 32 evaluable patients who received continuous daily administration of 8 X 10(6) U/m2 to 12 X 10(6) U/m2 of interferon for 4 weeks was 9.4%. Six of 30 patients (20%) were demonstrated responders in the case of the intermittent administration of 40 X 10(6) U/m2 of interferon on each of days 1 to 5, 15 to 19, 29, 31, 33, 43, 45, and 47 over an 8-week period. One of the responders achieved a complete response (CR). The patients tolerated this dose of interferon gamma well. Sites that responded to treatment were the lungs, lymph nodes, and brain. Major adverse effects included fever (86.8% of patients), anorexia (67.1%), fatigue (53.9%), and leukopenia (42.1%). No life-threatening side effects appeared. High doses of recombinant human interferon gamma have an antitumor activity against renal cell carcinoma. PMID- 3111678 TI - Immunologic and immunohistologic analysis of 27 cases with thyroid lymphomas. AB - Twenty-seven patients with stages I or II thyroid lymphomas were investigated immunologically. Approximately 60% of these patients had a goiter for longer than 1 year. Both the tests for serum antithyroid antibodies and histologic findings of the resected specimens showed that chronic lymphocytic (autoimmune) thyroiditis was usually present. The tumors were classified histologically as seven cases of follicular lymphomas and 20 cases of diffuse lymphomas. Immunocytologic study on suspended cells and immunohistologic study on frozen tissue sections showed that neoplastic cells in 22 of 27 cases expressed restricted immunoglobulin light chains. In remaining five cases, the neoplastic cells reacted with B-1, Leu-10, and/or Leu-14. These results indicate that thyroid lymphomas are exclusively B-cell-derived tumors. PMID- 3111679 TI - Relationship between fecal neutral steroid concentrations and malignancy in colon cells. AB - Analysis of total and individual fecal neutral steroids in different groups of intestinal pathology from 105 patients was performed to investigate a relationship between neutral steroid concentration and malignant potentiality of colon cells. The fecal concentration of total neutral steroids was significantly higher in patients with colon cancer (57.3 +/- 2.4 mmol/kg of wet feces) and patients with malignant degenerative polyps at Stage I or II (49.5 +/- 2.9) compared with controls (36.9 +/- 3.5) as well as patients with adenomatous polyps (22.4 +/- 2.0). Moreover, a significant correlation was found between total neutral steroid concentrations and coprostanol concentrations in patients with colon cancer (r = 0.928) and in patients with malignant polyps (r = 0.915). Coprostanol results only from the biohydrogenation of delta 5-3 beta-OH steroids by anerobic bacteria because the analysis of a malignant colon tumor in comparison with a healthy colon wall showed that cholesterol is the only steroid included in membrane cells, and that the incubation of Clostridium or Bacteroides with delta 5-3 beta-OH steroids, such as cholesterol (steroid of animal origin) or beta-sitosterol (steroid of plant origin) converts these steroids into coprostanol at a level of efficiency greater than 45%. The findings suggest that high levels of coprostanol reflecting a high growth of anerobic bacteria through the gut are related to the malignant potentiality of colon cells. The screening of neutral fecal steroids should provide a valuable parameter for predicting the malignancy of colon cells. PMID- 3111680 TI - Prostaglandin H synthase-catalyzed metabolism and DNA binding of 2-naphthylamine. AB - The oxidation of the bladder carcinogen 2-naphthylamine (2-NA) by prostaglandin H synthase (PHS) in vitro was examined. Oxygen uptake studies of 2-NA oxidation in the presence of glutathione, as well as extensive product analysis data, are consistent with a one-electron mechanism of 2-NA oxidation by PHS. The formation of 2-nitrosonaphthalene is not observed under any condition. Metabolism studies with a purified PHS preparation confirm that 2-NA oxidation is dependent upon the peroxidase activity of the enzyme complex, and that a variety of organic hydroperoxides may support the reaction. Horseradish peroxidase oxidizes 2-NA to the same products but, depending on pH, in very different proportions from those obtained with PHS. Oxidation of 2-NA by a one-electron chemical oxidant results in a product profile similar to that obtained in the enzymatic systems. The above data are consistent with a one-electron mechanism of 2-NA oxidation by PHS. The metabolism data provide evidence for the formation of two types of potentially reactive electrophiles: 2-imino-1-naphthoquinone and a free radical species. We further examine the time course of covalent binding of [3H]2-NA products to DNA in vitro, and compare this with the reaction of authentic [3H]2-amino-1-naphthol (2-A-1-N) product(s) with DNA and protein. A significant amount of the PHS catalyzed binding of 2-NA to DNA is derived from a short-lived intermediate; furthermore, the time course of binding is very rapid. Conversely, the binding to DNA of 2-A-1-N (presumably in the form of 2-imino-1-naphthoquinone) occurs to a lower extent and is not time dependent under the conditions studied. 2-A-1-N binds to protein, however, at a rapid rate and to three orders of magnitude greater extent than to DNA. The PHS-catalyzed binding of 2-NA to DNA was studied under several conditions; binding was shown conclusively to result from the peroxidase activity of the PHS complex. In addition, greater levels of binding were observed at pH 5.0 than at pH 7.6, and when catalyzed by horseradish peroxidase/H2O2 rather than PHS. These are conditions under which 2-A-1-N formation is negligible or nonexistent. These results demonstrate that in the PHS system, a reactive product(s) in addition to 2-A-1-N is generated which binds to DNA, and that this product is probably a free radical.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3111681 TI - Effects of difluoromethylornithine and dicyclohexylammonium sulfate on the transformed state of AKR-MCA cells. AB - The effect of two inhibitors of polyamine biosynthesis, difluoromethylornithine and dicyclohexylammonium sulfate, on the transformed fibroblastic cell line AKR MCA and its parental counterpart AKR-2B was investigated. Treatment of monolayer AKR-MCA cells with either agent results in morphological changes akin to AKR-2B; the cells appear to be flattened with a polygonal shape. The ability of the inhibitors to alter the phenotype is lost when the cells are cocultured with polyamines. More specifically, putrescine and spermidine abrogate the effects of difluoromethylornithine while only spermidine is effective in reversing the dicyclohexylammonium sulfate induced phenomenon. Further evidence that these enzyme inhibitors are reversing the transformed state of AKR-MCA is obtained from soft agarose experiments. AKR-MCA cells will generate colonies only in the absence of either difluoromethylornithine or dicyclohexylammonium sulfate. Polyamine levels were determined in parental AKR-2B and AKR-MCA cells. The levels of putrescine and spermine were similar in both cell types. In contrast, significantly more (P less than or equal to 0.01) spermidine was expressed by the malignant line [7.3 +/- 0.8 (SD) nmol/10(6) cells] when compared with the untransformed AKR-2B (5.4 +/- 0.8 nmol/10(6)) cells. Intracellular putrescine and spermidine were sensitive to difluoromethylornithine, dicyclohexylammonium sulfate, and dimethylformamide, a planar, polar solvent which has been reported to "normalize" the transformed phenotype. AKR-MCA treated with difluoromethylornithine or dimethylformamide manifested time dependent reductions in both polyamines which preceded morphological changes. Dicyclohexylammonium sulfate similarly caused a 70% reduction in spermidine, but in contrast to the other agents there was a marked accumulation of putrescine. These data concur with the established molecular actions of the two enzyme inhibitors as blockers of ornithine decarboxylase (difluoromethylornithine) and spermidine synthase (dicyclohexylammonium sulfate). The normalizing capacity of dimethylformamide was not compromised by cotreatment with putrescine or spermidine. Both difluoromethylornithine and dicyclohexylammonium sulfate inhibited the growth of monolayer AKR-2B and AKR-MCA. In view of the well documented cytostatic effects of polyamine inhibitors, it is suggested that a decrease in growth by these agents triggers a more normal phenotype in AKR-MCA cells. PMID- 3111682 TI - Normal cytotoxic response of skin fibroblasts from patients with Li-Fraumeni familial cancer syndrome to DNA-damaging agents in vitro. AB - Skin fibroblasts from patients with the Li-Fraumeni familial cancer syndrome have been reported to show abnormalities in their response to X-irradiation. We have examined the response of fibroblasts from affected and nonaffected individuals in three families to treatment with four DNA-damaging agents: X-rays, UV light, N methyl-N'-nitro-N-nitrosoguanidine, and mitomycin C. Test cells along with additional cell bank control strains were received coded and blinded. The same strains were studied on 2 or 3 separate occasions; each of these groups was coded differently. The cytotoxic effects of the four agents were examined by a colony formation assay. Sensitivity to the induction of chromosomal aberrations by X rays was also measured. In all cases, the response of cells from affected individuals did not differ significantly from that of cells from unaffected (not a risk) family members nor of cell bank controls. The response of somatic cells from members of Li-Fraumeni cancer families to DNA-damaging agents does not appear to be a fruitful approach to the detection of at-risk individuals. PMID- 3111683 TI - Effects of timing and quantity of chronic dietary ethanol consumption on azoxymethane-induced colonic carcinogenesis and azoxymethane metabolism in Fischer 344 rats. AB - Epidemiological studies have shown an association between consumption of alcoholic beverages and carcinoma of the large bowel, but studies in experimental models of colonic carcinogenesis have yielded conflicting results. We assessed the effects on azoxymethane-induced colonic carcinogenesis of both timing of chronic dietary ethanol consumption relative to carcinogen administration and quantity of ethanol consumption. Ten-week-old male Fischer 344 rats were given 11%, 22%, or 33% of calories as reagent ethanol or no ethanol by pair feeding with Lieber-DeCarli-type liquid diets providing comparable total carbohydrates, proteins, fats, and calories. Ten weekly s.c. injections of the bowel carcinogen azoxymethane (AOM), 7 mg/kg, were given to all rats in weeks 1-10. Three experimental groups were given their respective ethanol diet during acclimatization and AOM administration (preinduction and induction phases) and then were given the no-ethanol diet from week 11 until sacrifice in week 26 (postinduction phase). Three other groups received the no-ethanol diet during acclimatization and AOM administration and then were changed to their respective ethanol diet until sacrifice. The control AOM group received the no-ethanol diet throughout the study. Suppression of colonic tumorigenesis occurred in the groups with high levels of chronic dietary ethanol consumption during acclimatization and AOM administration: in the 33% and 22% diet groups, the prevalence of colonic tumors was 3% and 20% as compared with 50% in control (P less than 0.001 and P less than 0.02, respectively). Tumorigenesis in the left colon was more affected than in the right colon, as tumor prevalence in the left colon was decreased in both the 33% and 22% diet groups (0% in both versus 24% in control, P less than 0.005), whereas prevalence in the right colon was decreased only in the 33% diet group (3% versus 38%, P less than 0.001). By contrast, prevalence of colonic tumors in the 11% diet group was not significantly different from control. Chronic dietary ethanol consumption after AOM administration had no effect on tumor outcome, regardless of quantity of consumption. In an analogous study of [14C]AOM metabolism in rats fed the 33% diet during acclimatization and AOM administration, 14CO2 was exhaled at a slower rate than in rats fed no-ethanol diet (P = 0.05), indicating suppression of AOM metabolism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3111684 TI - Separation and functional studies of the human lymphokine-activated killer cell. AB - Cell separation studies were undertaken in an attempt to purify the lymphokine activated killer (LAK) precursor cell. Null cells, prepared by the sequential depletion of monocytes, T- and B-lymphocytes from human peripheral blood mononuclear cells, were found to be potent mediators of LAK activity. Such preparations were Leu-11+ but Leu-4- and displayed high levels of natural killer activity. Incubation of these cells with recombinant interleukin 2 (IL-2) for periods in excess of 24 h induced LAK lysis of fresh tumor targets which were resistant to lysis by unstimulated null effectors. In contrast, lymphocytes which formed high affinity rosettes with sheep RBC (E+ lymphocytes) were poor mediators of both natural killer and LAK activity. Interleukin 2 stimulated null cells, retained a Leu-11+, Leu-4- phenotype, and expressed only low levels of receptors for IL-2 and transferrin. An increase in the number of binding sites, on null cells but not on T-cells, for Vicia villosa lectin with IL-2 stimulation was noted. Following IL-2 stimulation, null and T-cells were able to conjugate to K562 and fresh tumor but not to autologous lymphoblast targets. PMID- 3111686 TI - Enhanced in vitro proliferation and in vivo tumorigenic potential of mammary epithelium from BALB/c mice exposed in vivo to gamma-radiation and/or 7,12 dimethylbenz[a]anthracene. AB - Virgin female BALB/c mice were exposed in vivo to whole body gamma-radiation and/or to 7,12-dimethylbenz[a]anthracene (DMBA) p.o. Mammary epithelial cells were isolated and assayed for carcinogen altered cell populations both in vitro by an epithelial focus assay and in vivo by injection into cleared fat pads of syngeneic host mice. Five groups of mice were exposed as follows: (a) sham controls; (b) 50-rad gamma-radiation; (c) 100-rad gamma-radiation; (d) 75 micrograms DMBA; or (e) 50-rad gamma-radiation followed in 1 week by 75 micrograms DMBA. Mammary epithelial cells were isolated and assayed at 24 h and at 1, 4, 16, and 52 weeks after in vivo exposure. Four to 12 mice per treatment per time point were individually assayed. Altered in vitro growth potential was characterized by the proliferation of carcinogen exposed (but not control) cells as epithelial foci which persisted at least 12 weeks in primary culture. Epithelial foci which could then be subcultured at least four times were termed subculturable epithelial foci. Altered in vivo morphogenic potential was characterized by dysplastic or neoplastic growth in host fat pads. With increased time in situ between exposure and assay, cell populations emerged which exhibited both increased in vitro subculturability and enhanced tumorigenic potential including a host response upon injection in vivo. Further, combined radiation and DMBA resulted in higher frequencies of subculturable epithelial foci than either treatment alone. The relevance of these progressive cellular changes to the process of mammary tumor development is discussed. PMID- 3111685 TI - Interspecies differences in the major DNA adducts formed from benzo(a)pyrene but not 7,12-dimethylbenz(a)anthracene in rat and human mammary cell cultures. AB - Mammary epithelial cells from rats and humans show both quantitative and qualitative species- and carcinogen-specific differences in their abilities to activate benzo(a)pyrene (B(a)P) and 7,12-dimethylbenz(a)anthracene (DMBA). Previous studies of the DNA binding of these compounds in mammary epithelial cells demonstrated that rat cells bound relatively more DMBA than B(a)P to DNA under identical treatment conditions, while the opposite pattern was exhibited by human mammary epithelial cells. The specific DNA adducts formed in these cells after 24-h incubations with [3H]DMBA and [3H]B(a)P were analyzed to determine if there were qualitative as well as quantitative differences in the amounts of individual adducts. Similar proportions of specific DMBA-DNA adducts were found in both rat and human cells, although the total amount of adducts formed was significantly higher in the rat cells. In contrast, an essentially qualitative species-specific difference was observed in the major B(a)P-DNA adduct present in the rat and human cells. The major B(a)P adduct formed in the human mammary epithelial cells was identified as the (+)-anti-B(a)P-7,8-dihydrodiol-9, 10 epoxide(BPDE)-deoxyguanosine adduct. However, this adduct was formed at very low levels in the rat mammary epithelial cells. The rat cells contained a large proportion of syn-BPDE adducts, and other unidentified B(a)P-DNA adducts. The high level of the (+)-anti-BPDE-deoxyguanosine adduct in the human but not the rat mammary cells is consistent with the potential role of (+)-anti-BPDE in the high mutagenic activity of B(a)P in the cell-mediated mutagenesis assays using the human mammary cells as activators, and the low mutagenic activity of B(a)P when rat cells were used as activators. The quantitative differences in the activation of DMBA by cells from these two species are also consistent with the cell-mediated mutagenic activities of DMBA using these cells as activators. These results suggest that the higher carcinogenic activity of DMBA compared to B(a)P in the rat mammary gland may not be indicative of the relative carcinogenic potencies of these compounds for human mammary cells. PMID- 3111687 TI - High-dose i.v. thiotepa and cryopreserved autologous bone marrow transplantation for therapy of refractory cancer. AB - Twenty-five patients with malignancies resistant to conventional chemoradiation therapy or for which no effective therapy is known were treated with escalating doses of thiotepa (135-1215 mg/m2 iv over 3 days) followed by reinfusion of previously cryopreserved autologous bone marrow. The hematological and nonhematological toxic effects, therapeutic effects, and pharmacokinetics of this regimen were evaluated. Granulocyte (greater than 500/microliter) and platelet (greater than 20,000/microliter) count recovery occurred at a median of 16 (range, 11-38) and 18.5 (range, 11-40) days after marrow reinfusion, respectively. Six patients experienced severe infection, four of which were fatal. One patient died due to intracranial hemorrhage. Toxicity to the gastrointestinal and central nervous systems was dose-limiting, and the maximum tolerated dose of thiotepa was 1005 mg/m2. Objective tumor regression occurred in six of the patients. Serum thiotepa concentration peaked immediately after infusion and declined rapidly in a biphasic manner. No relationship between thiotepa serum concentration or pharmacokinetic parameter estimates was observed for tumor response or toxicity. High-dose thiotepa and autologous bone marrow transplantation may represent an alternative therapeutic modality for patients with advanced cancer. PMID- 3111688 TI - [Exertion 2-dimensional echocardiography in the evaluation of anti-anginal drugs]. PMID- 3111690 TI - Controlled study of the haemodynamic effects of isosorbide 5-mononitrate in acute myocardial infarction. AB - In view of the favourable results of the short-term therapy of acute myocardial infarction (AMI) with glyceryl-trinitrate (GTN) infusion, we undertook a randomized study to test the hypothesis whether the administration of a single dose of isosorbide 5-mononitrate (IS 5-MN) given orally would have the same favourable haemodynamic effect as observed with GTN infusion. For this purpose we evaluated the haemodynamic effects of IS 5-MN compared to isosorbide dinitrate (ISDN), observed in the same group of patients. 10 patients (8 males, 2 females) aged 50-76 years (mean 63) with AMI (7 anterior, 3 inferior) admitted to the coronary care unit within 48 h from onset of symptoms were entered into this single-blind randomized study; at the time of study entry, 8 patients were in Killip class I, and 2 patients in Killip class II. All drugs with haemodynamic effects were withdrawn 12 h before the study started. Both the haemodynamic profile and the clinical status were stable in all patients. Haemodynamic parameters were recorded with a Swan-Ganz thermodilution catheter, cardiac output was measured by the thermodilution method, and the left ventricular ejection time was calculated according to the Weissler method. The echo left ventricular end diastolic diameter was measured by evaluation of the M-mode echocardiographic recording.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111689 TI - Antianginal efficacy and tolerability of 50 mg sustained-release isosorbide 5 mononitrate in an open twelve-month observation study. AB - Thirty-eight male patients with coronary heart disease were treated with 1 capsule Elantan Long (50 mg IS 5-MN) daily over a period of 1 year. Both before and after the 12-month therapy, a placebo phase of 1 week each was carried out. Two hours after drug administration (Elantan Long and placebo, respectively) a standardized exercise test was carried out at the end of each placebo period and every 3 months during the treatment with Elantan Long. Furthermore, anginal attacks and nitroglycerin consumption were recorded throughout the whole study. Under individually maximum comparable load of 81 +/- 20 W, mean ST-segment depression decreased from 0.19 mV (baseline value) to 0.05 mV respectively, after 12 months of therapy, a decrease of 73% (p less than 0.001). The measurement during the last placebo phase with an increase of ST-segment depression up to 0.18 mV still remained slightly below the baseline value. The incidence of anginal attacks highly significantly decreased from 8.4 +/- 2.0 to 2.0 +/- 1.2 attacks/week after 12 months' treatment (p less than 0.001). Correspondingly, additional nitroglycerin consumption also diminished by 76%. Both values increased to 7.1 +/- 1.9 after the following placebo phase. With the exception of 2 cases the tolerability was judged to be 'very good' and 'good'. During long term therapy with Elantan Long, no sign of tolerance development was found; on the contrary, a further increase in efficacy was seen in the course of therapy. PMID- 3111691 TI - Platelets and arachidonic acid derivatives in myocardial ischemia in animal models. AB - The accumulated evidence indicates that myocardial ischemia is a complex process involving dysfunction of various cellular elements as well as coronary narrowing. A homeostatic imbalance of endogenously produced vasoactive compounds, released locally as a result of intricate platelet, neutrophil, and endothelial cell-cell interactions, participates in the eventual outcome of tissue ischemia. This imbalance is frequently caused by the formation of an intracoronary platelet thrombus. Therapeutic strategy aimed to modulate intrinsic eicosanoid biosynthesis and neutrophil platelet function may reduce ischemia and benefit patients with ischemic heart disease. PMID- 3111692 TI - Pharmacology of platelet-inhibitory drugs, anticoagulants, and thrombolytic agents. PMID- 3111693 TI - Embolization of a subclavian artery aneurysm with steel coils and thrombin. AB - Subclavian artery aneurysms are rare lesions usually treated by surgical excision or ligation. Steel coils were used successfully to treat a rapidly enlarging subclavian aneurysm in a patient deemed unsuitable for surgery. Because of a profound, uncorrectable coagulopathy, thrombin was required to obtain effective thrombosis. PMID- 3111694 TI - Aortic dissection, a diagnostic dilemma: case report. AB - A case of type I (type A) aortic dissection proved by postmortem examination could not be fully delineated relative to the type of dissection by dynamic CT as well as three positive contrast aortograms. Small tears in the ascending aorta and their strategic locations can escape even intensive radiologic evaluation. We present a case in which medical therapy was provided and, inappropriately, surgery was not performed. PMID- 3111695 TI - Pseudoaneurysm of internal carotid artery secondary to tonsillectomy: combined radiologic and surgical treatment. AB - An unusual case of pseudoaneurysm of the internal carotid artery secondary to tonsillectomy is reported. The management consisted of combined intraoperative transcatheter embolization with surgical ligation of the internal carotid artery. PMID- 3111696 TI - Inferior thyroid artery arising from common carotid artery with aberrant right subclavian artery. AB - We describe an unusual variant in the blood supply to the inferior portion of the right thyroid gland encountered during parathyroid localization studies. A brief review of other possible variants is given. PMID- 3111697 TI - Embolization of blunt trauma in the pediatric patient. AB - The use of embolization for control of hemorrhage following blunt trauma is well accepted in the adult population. This paper describes 2 cases in which embolization techniques were used successfully to control hemorrhage following blunt trauma in pediatric patients. PMID- 3111698 TI - Two-dimensional echocardiography in the diagnosis of intracardiac masses: a prospective study with anatomic validation. AB - The accuracy of two-dimensional echocardiography in the detection of intracardiac masses was verified in 334 patients who underwent cardiac catheterization in our laboratory over 21 consecutive months. A complete two-dimensional echocardiographic (2DE) examination was performed a day before catheterization. The presence or absence of a mass was verified at surgery in 77 patients who successively underwent mitral or aortic valve replacement (51), left ventricular aneurysmectomy with or without myocardial revascularization (25), and resection of atrial myxoma (2). In 32 patients 2DE revealed the presence of a mass-left or right atrial thrombi in 12, left atrial myxoma in 2, left ventricular thrombi in 16, and endocardial vegetations in 2. The other 45 patients were free of intracardiac masses on 2DE. Anatomic verification at surgery revealed the presence of an intracardiac mass in 34 patients. In 30 (true positives) of these, 2DE revealed the mass as well, and in 4 (false negatives) the presence of a mass had not been identified by 2DE. In 2 patients (false positives) the predicted mass was not found at surgery. Absence of a mass was correctly predicted by 2DE in 41 patients (true negatives). Thus 2DE detected intracardiac masses with sensitivity of 88.2% and a specificity of 95.3%. We recommend that 2DE be performed in all patients prior to hemodynamic study and/or cardiac surgery to enable safer management of patients with intracardiac masses during cardiac catheterization and/or cardiac surgery. PMID- 3111699 TI - Illustrative cases in pericardial effusion misdetection: correlation of echocardiography and CT. AB - Eight equivocal two-dimensional echocardiograms with concurrent CT scans were evaluated to identify potential pitfalls in pericardial effusion detection. By echocardiography, two pleural effusions were felt to be pericardial, two hemopericardiums were interpreted as normal myocardium, three loculated pericardial effusions were not seen or were misinterpreted as other mediastinal collections, and one epicardial lipoma was called a pericardial effusion. When the clinical suspicion for pericardial effusion does not correlate with echocardiographic findings, CT scanning may be the definitive arbiter of pericardial disease. PMID- 3111701 TI - Improved technique for rethreading and modifying Cope loop retention catheters. AB - In patients with high proximal biliary obstructions, the standard Cope biliary retention catheter may not drain the proximally obstructed bile ducts. Placing additional side holes proximally in the catheter will usually cut the retention string. We have therefore devised a simple technique for removing the string prior to making the side holes and replacing it, using the stiffening cannula provided with the catheter. The technique has proved successful in 5 cases. PMID- 3111700 TI - Inadvertant atrial fixation of a Swan-Ganz catheter by suture and a method for its percutaneous removal. AB - A patient with type I dissection of the thoracic aorta inadvertently had a Swan Ganz catheter sutured to the right atrium during surgical repair of the dissection. A method for its removal using percutaneous passage of a No. 15 scalpel blade is described. The hazards of Swan-Ganz catheters are explored, and the changing roles of nonsurgical interventional procedures are discussed. PMID- 3111702 TI - Effects of a levo-5-hydroxytryptophan-dihydroergocristine combination on depression and neuropsychic performance: a double-blind placebo-controlled clinical trial in elderly patients. AB - Fifty elderly patients (mean age, 68 years) affected by depression were treated with a combination (P3007) containing 3 mg of dihydroergocristine and 100 mg of levo-5-hydroxytryptophan or placebo for 60 days in a double-blind trial. Efficacy of treatment was evaluated by means of neuropsychic tests and rating scales for depression before treatment and after 30 and 60 days. Patients treated with the drug combination showed significant improvements in their depressive state and psychic performance, whereas no change was observed in patients receiving placebo. The treatment was well tolerated. PMID- 3111703 TI - Enprostil reduces G-cell hyperplasia and hypergastrinemia in duodenal ulcer. AB - A 42-year-old man with a 26-year history of duodenal ulcer volunteered for a 24 hour intragastric pH monitoring study, at which time his fasting gastrin concentration was found to be elevated. Secretin injection decreased the serum gastrin concentration. When not on treatment his total gastrin, gastrin-17 (G 17), and gastrin-34 (G-34) response to a protein-containing breakfast was marked. Immunocytochemical staining of antral biopsies showed hyperplasia of gastrin containing cells, more pronounced for G-17 than for G-34. Cimetidine or cimetidine plus pirenzepine increased 24-hour intragastric pH, whereas pirenzepine alone rendered the gastric contents more acidic, particularly overnight. The total serum gastrin concentrations increased after meals and were unaffected by cimetidine or pirenzepine; enprostil, however, reduced the postprandial increase in total gastrin, G-34, and G-17. After six weeks of treatment with enprostil, the number of cells containing G-17 and G-34 was reduced. The findings show that G-cell hyperplasia may occur in the presence of a normal fasting serum gastrin concentration; fasting serum gastrin concentrations may fluctuate widely over time; the food-stimulated increase in G-17 was greater than that for G-34, and is associated with more pronounced antral hyperplasia for G-17 and G-34; and enprostil blunts the postprandial increase in G-17, G-34, and total gastrin. These observations suggest that enprostil may reduce G-cell hyperplasia and hypergastrinemia. PMID- 3111704 TI - Safety of an intravenous immunoglobulin preparation: lack of seroconversion for human immunodeficiency virus antibodies. AB - A retrospective analysis of 18 patients who had received a human intravenous immunoglobulin (IGIV) preparation was undertaken to ascertain the safety of this preparation with respect to transmission of human immunodeficiency virus (HIV), the virus that causes the acquired immune deficiency syndrome (AIDS). Patients were followed up by means of periodic enzyme-linked immunosorbent assay (ELISA) for the presence of circulating antibodies against HIV; a negative ELISA was evidence that HIV had not been transmitted to the recipients of IGIV. Results in 16 patients were negative, and two patients were determined to have had false positive ELISAs because the Western blot test was negative for seroconversion. It is thus concluded that the IGIV product tested has little or no potential for transmitting HIV. PMID- 3111705 TI - Efficacy of oral administration of etidronate disodium in maintaining normal serum calcium levels in previously hypercalcemic cancer patients. AB - As part of a multicenter trial of etidronate disodium for control of hypercalcemia in patients with malignancies, patients achieving normocalcemia within seven days after starting intravenous therapy with etidronate disodium plus saline were enrolled into a double-blind, placebo-controlled trial of oral etidronate disodium to maintain normocalcemia. By random assignment, patients received either oral etidronate disodium, 20 mg/kg/day, or placebo for up to three months. Efficacy was evaluated after 30 days of maintenance therapy: patients who were normocalcemic on day 30 were considered treatment successes. Of 81 patients who entered this phase of the study, 63 were evaluable for efficacy. Analysis of this group revealed that significantly (P less than 0.01) more patients in the etidronate disodium group (35%) than in the placebo group (6%) were normocalcemic at day 30. Life-table analysis of response indicated that patients treated with etidronate disodium maintained normocalcemia significantly (P less than 0.01) longer than did patients receiving placebo (median, 29 days versus 11 days). These results suggest that in patients whose calcium levels were normalized with IV etidronate disodium, oral etidronate disodium maintained normocalcemia significantly longer than no maintenance therapy in patients treated for hypercalcemia secondary to malignancy. PMID- 3111706 TI - Early experience with the use of anti-inhibitor coagulant complex to treat bleeding in hemophiliacs with inhibitors to factor VIII. AB - Early clinical experience with anti-inhibitor coagulant complex in the treatment of bleeding in patients with factor VIII inhibitors is described. Sixty patients with a total of 120 bleeding episodes were studied. Satisfactory responses were obtained in 86.6% of bleeding episodes. Efficacy was slightly better in open bleeding than in closed bleeding. Higher doses were significantly better than lower doses in treating open bleeding. The incidence of adverse reactions was low. The results reported support the safety and efficacy of anti-inhibitor coagulant complex in the treatment of bleeding in patients with factor VIII inhibitors. PMID- 3111707 TI - Impact of changes in intracellular Ca2+ and K+ concentration on the development of hormonal imprinting in a Tetrahymena model system. PMID- 3111708 TI - Is adult-type hypolactasia in the intestine of mammals related to changes in the intracellular processing of lactase? PMID- 3111709 TI - Chemoattraction enrichment of thymus-homing bone marrow cells. AB - It has been reported that a population of cells from mouse bone marrow migrates to supernatant made from the incubation of minced fragments of new-born mouse thymuses and that the migrated population is enriched for immature lymphoid cells. In the present study, we show that this method enriches for thymic-homing cells. Migration-enriched cells were labelled with fluorescein isothiocyanate (FITC) and were injected into the tail veins of lethally irradiated mice. Cell suspensions of the thymuses from these experimental mice had 8.1 +/- 1.8% fluorescing cells compared to control mice given equal numbers of non-migration enriched FITC labelled cells which had 2.4 +/- 1.7% positive cells. PMID- 3111710 TI - Precocious development of lectin (Ulex europaeus agglutinin I) receptors in dome epithelium of gut-associated lymphoid tissues. AB - Dome epithelium (DE), the tissue covering lymphoid domes of gut-associated lymphoid tissues, was examined in both adult and neonatal rabbit appendix or sacculus rotundus to determine if dome epithelial cells matured earlier than epithelial cells covering adjacent villi. The localization of well-differentiated epithelial cells in rabbit gut-associated lymphoid tissues (GALT) was accomplished histochemically by use of molecular probes: fluorescein isothiocyanate or horseradish peroxidase conjugates of Ulex europaeus agglutinin I (UEA), a lectin specific for terminal L-fucose molecules on certain glycoconjugates. The villus epithelial cells of newborn and 2-, 5-, or 10-day-old rabbits did not bind UEA, but between the twelfth and fifteenth days of postnatal life, UEA receptors were expressed by well-differentiated villus epithelial cells. In contrast to villus epithelium, DE in appendix and sacculus rotundus of neonatal rabbits expressed UEA receptors two days after birth, a feature that distinguished the DE of neonatal GALT for the next two weeks. In adult rabbits, UEA receptors were associated with dome epithelial cells extending from the mouths of glandular crypts to the upper domes; in contrast to the domes, UEA receptors were only present on well-differentiated epithelial cells at the villus tips. Results suggested that in neonatal rabbits most dome epithelial cells developed UEA receptors shortly after birth, reflecting precocious development of DE as compared to villus epithelium. In adult rabbit dome epithelium UEA receptors appeared on dome epithelial cells as they left the glandular crypts, representing accelerated epithelial maturation. PMID- 3111712 TI - Response of pituitary thyrotrophs to thyrotrophin-releasing hormone in Snell dwarf mice. AB - The effect of thyrotrophin-releasing hormone (TRH) on pituitary thyrotrophs was investigated in Snell dwarf mice (dw/dw) that are genetically deficient in thyrotrophin (TSH) and in normal animals of the same strain. The normal animals were treated with either saline or 10 micrograms TRH per day for 2 weeks, while the dwarf mice were given daily injections of saline, 10 micrograms TRH for 2 weeks or 10 micrograms for 6 weeks. At the end of each experimental period, the pituitary glands were removed and fixed for light-microscopic analysis using immunocytochemistry, or for transmission electron-microscopic study. Compared to thyrotrophs observed in the pituitary glands of untreated normal mice, thyrotrophs in TRH-treated normal mice appeared to be more numerous by immunocytochemistry and showed signs of stimulation by electron microscopy. In contrast, immunostainable thyrotrophs could not be identified in the pituitary glands of untreated or TRH-treated dwarfs. However, a few cells exhibiting ultrastructural features of stimulated thyrotrophs, were noticeable in the dwarfs following TRH administration. Thus, while failing to induce the synthesis of immunoreactive TSH under the applied experimental conditions, exogenous TRH appeared to elicit differentiation of thyrotroph precursors into ultrastructurally recognizable thyrotrophs. The discrepancy between the immunocytochemical and ultrastructural findings remains unresolved; more work is required to clarify the question as to why ultrastructural maturation of thyrotrophs was unaccompanied by the production of immunoreactive TSH. PMID- 3111711 TI - Diminished steroidogenic response of hamster granulosa cells to estrogen in vitro. AB - We have previously demonstrated that estrogen can exert inhibitory or atretogenic effects on the ovaries of both rats and rhesus monkeys in vivo. This study was designed to test whether the hamster (Mesocricetus auratus) is an appropriate model in which to test the effects of estrogens (diethylstilbestrol and estradiol 17 beta) on steroid accumulation by ovarian granulosa cells in vitro, and whether the effects are similar to those demonstrated for other species in vivo. Immature female hamsters were injected with pregnant mare's serum gonadotropin at 28 to 30 days of age. Animals were sacrificed and follicular contents aspirated three days later. Granulosa cells were either left untreated or treated with diethylstilbestrol or estradiol (1 X 10(-7) M) in vitro for 72 h in the presence of androstenedione (1 X 10(-7) M, and in the presence or absence of serum (10%) or human follicle-stimulating hormone (20 ng/ml), and long-term accumulation of estrogen and progesterone was determined. Diethylstilbestrol inhibited accumulation of estrogen regardless of the presence or absence of follicle stimulating hormone. In contrast, only estradiol plus follicle-stimulating hormone augmented accumulation of progesterone by granulosa cells. These findings that estrogen can be non-stimulatory or inhibitory to function of granulosa cells in vitro parallel those shown in vivo. Our experimental approach may therefore represent an appropriate model for study of the direct effects of estradiol on the function of granulosa cells. PMID- 3111714 TI - Bilateral cerebral occipital calcifications and migraine-like headache. AB - Computed tomography scanning in two young patients with recurrent, pulsating, migraine-like headache showed parieto-occipital calcifications. One patient presented with an atypical form of the Sturge-Weber syndrome, and the other with celiac disease and folic acid deficiency. The clinical features were analyzed and compared with those in other cases reported in the recent literature which have shown bioccipital calcifications but no cutaneous angiomas, sometimes associated with visual and/or intelligence deficit and epilepsy. Finally, the possible connection between cerebral calcifications and headache is discussed. PMID- 3111713 TI - Impaired calcium mobilisation in the 7315a prolactin-secreting pituitary tumour. AB - The 7315a tumour secretes prolactin, but is refractory to enhancement of prolactin release by thyrotrophin-releasing hormone (TRH). In order to investigate further this refractoriness of the 7315a tumour cell, we compared cells from the tumour and from the normal pituitary with regard to TRH-enhanced fractional 45Ca2+ efflux and inositol phosphate production. TRH caused a large efflux of calcium from normal pituitary cells, but only mildly enhanced calcium efflux from the tumour cells. In contrast, TRH enhanced total inositol phosphate generation in both groups of cells to a similar degree. We therefore conclude that prolactin release from 7315a tumour cells is refractory to TRH due, at least in part, to impaired mobilisation of intracellular calcium by inositol phosphates. PMID- 3111715 TI - Migraine and the lupus anticoagulant. Case reports and review of the literature. AB - Lupus anticoagulants (LA) are antiphospholipid serum immunoglobulins generally associated with autoimmune conditions, especially systemic lupus erythematosus (SLE). They have recently been linked to thrombotic events, including stroke. A possible association of migraine with LA is now forwarded with the presentation of two cases and a literature review. Our two patients, both in their forties, had migrainous phenomena without SLE or thrombotic events. Eight other cases were found in the literature, suggesting more than a chance association. Relevance to migraine pathophysiology is discussed and may come from the ability of the LA to alter prostaglandins and platelet activity and to interact with neuronal phospholipids. Further, larger studies are needed to support this association. PMID- 3111716 TI - The achaete-scute gene complex of D. melanogaster: conserved domains in a subset of genes required for neurogenesis and their homology to myc. AB - We have determined the nucleotide sequence of two transcription units of the AS-C and shown that their potential protein coding regions share two principal domains of homology. Both domains are conserved within the myc protein family, and one of them is highly homologous with the consensus for protein tyrosine kinase substrates. We show in addition that at least one of these domains is shared with other transcription units within the AS-C, some of which were not previously known. We suggest that the AS-C encodes several homologous polypeptides, which represent a subset of a larger gene family. We propose that each member of the family functions at an equivalent stage of a unique morphogenetic operation involving the segregation of individual neural lineages from the epidermal anlage. PMID- 3111717 TI - Inhibition of endocytosis by anti-clathrin antibodies. AB - We examined the function of clathrin, a cytoplasmic protein associated with coated pits and vesicles, by introducing monoclonal antibodies into living cells and determining their effects on membrane transport. When anti-clathrin heavy chain antibodies were used, the following effects were observed: clathrin became aggregated in the cytoplasm, the number of coated pits on the plasma membrane was reduced, and adsorbtive endocytosis of Semliki Forest virus and fluid-phase endocytosis were decreased by 40%-50%. No change in transport of newly synthesized influenza hemagglutinin to the plasma membrane was observed. The results indicated that clathrin in CV-1 cells is involved in fluid-phase uptake and receptor-mediated endocytosis, but not in constitutive transport within the secretory pathway. PMID- 3111718 TI - Oncogenes take wing. PMID- 3111719 TI - Analysis of Kruppel protein distribution during early Drosophila development reveals posttranscriptional regulation. AB - We have examined the spatial and temporal patterns of expression of the Kruppel (Kr) protein, a gap gene product, during Drosophila embryogenesis. Antibodies directed against the Kr protein revealed patterns of nuclear staining that represent subpatterns of Kr transcript accumulation in particular tissues. This indicates that the distribution of Kr protein is not a direct response to Kr mRNA accumulation, and that Kr protein expression requires a second level of control in addition to spatially regulated transcription. Our data provide evidence for posttranscriptional control that may involve an intron present in the 5' region of one of the two Kr transcripts. The intron-containing transcript is the only potential source of new Kr protein synthesis after gastrulation. The finding of late and transient patterns of Kr activity in several tissues, such as the developing nervous system, amnion serosa, and muscle precursor cells suggests that Kr activity may be required in several developmental processes after segmentation has been completed. PMID- 3111720 TI - The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. AB - We have isolated the Drosophila melanogaster homolog (Dint-1) of int-1, a conserved cellular oncogene implicated in viral mammary tumorigenesis in mice. The deduced Dint-1 protein sequence contains 468 amino acids and starts with a hydrophobic leader; it is 54% identical to the int-1 sequence, and all 23 cysteine residues are conserved. The putative Drosophila protein has an extra sequence of 85 amino acids, encoded on an additional exon. Dint-1 is expressed throughout development, but transcripts are barely detectable in adult flies. Hybridization in situ to embryos reveals a segmented pattern of expression. We show that Dint-1 and the segment polarity gene wingless are identical and map to the same location. The sequence of the gene suggests that the Dint-1/wingless protein functions in morphogenesis as a signal in cell-cell communication. PMID- 3111722 TI - Identification of a major 50-kDa molecular weight human B-cell growth factor with Tac antigen-inducing activity on B cells. AB - A bioassay was developed using human small B cells adherent to anti-human IgM (anti-mu)-coated wells. These B cells were stimulated to proliferate by culture supernatants of concanavalin A (Con A)-activated human peripheral blood lymphocytes (Con A Sup) even in the presence of high concentrations of anti-mu coated on assay wells. Human B-cell growth factor (BCGF) activities were partially purified from Con A Sup. Preparative chromatography (Sephacryl S-200 and isoelectrofocusing) yielded a major peak of BCGF activity for B cells adherent to anti-mu-coated wells with a molecular weight of 50,000 (50 kDa) and a pI 7.6. The 50-kDa BCGF was further purified by sequential chromatography using DEAE-Sephacel, CM-Sepharose, Sephacryl S-200, CM-high performance liquid chromatography (HPLC), and hydroxyapatite (HA)-HPLC. The HA-HPLC-purified 50-kDa BCGF was free of interleukin-1 (IL-1), interleukin-2 (IL-2), and interferon activities, but could support growth of BCL1 cells, similar to BCGF-II. Neither IL-1 nor interferon-gamma had any growth-stimulating effect in our B-cell proliferation assay with or without BCGF in Iscove's synthetic assay medium. BCGF induced proliferation of B cells adherent to anti-mu-coated wells could be markedly augmented by the simultaneous or sequential addition of recombinant human IL-2 (rIL-2). When cultured for 3 days with 50-kDa BCGF, about 40% of B cells adherent to anti-mu-coated wells expressed Tac antigen, and monoclonal anti Tac antibody inhibited rIL-2 enhancement of proliferation of 50-kDa BCGF preactivated B cells. In addition, 50-kDa BCGF could induce Tac antigen on an Epstein-Barr virus-transformed B-cell line (ORSON) in the presence of a suboptimal dose of phorbol myristate acetate (PMA) and also on a natural killer like cell line (YT cells). We have therefore identified a major 50-kDa BCGF activity with Tac antigen-inducing activity that also has a synergistic effect with IL-2 on normal B-cell proliferation. PMID- 3111721 TI - Characterization of a T-cell determinant defined by a monoclonal antibody (TH5.2) which is involved in the interleukin-2-producing and proliferative capabilities of T cells. AB - Utilizing an OKT-4-positive human T-cell lymphoma cell line as immunogen, we have produced a monoclonal antibody (MAb), designated TH5.2, which is capable of augmenting the interleukin-2 (IL-2) production and proliferation of antigen activated T cells. TH5.2 MAb by itself is not mitogenic for T cells; the enhanced IL-2 production and proliferation requires costimulation with either antigen or mitogen. TH.2 MAb recognizes all peripheral blood T cells at varying intensities, but does not react with monocytes. Using dual-color fluorescence analysis, it was determined that TH5.2 MAb reacts at a higher intensity on Leu-3a-positive T cells compared to Leu-2a-positive cells. Sorting T cells on the basis of fluorescent intensity with TH5.2 MAb demonstrated that the T cells reacting at high TH5.2 intensity were able to respond to mitogen at a higher rate (5-10X), as well as produce higher concentrations of IL-2 in response to mitogen as compared to the low IL-2 intensity cells. Cytotoxically treating peripheral blood mononuclear cells (PBMC) with TH5.2 MAb plus complement, which resulted in an approximate 8% decrease in the total population, significantly reduced the ability of the cells to proliferate to both mitogen and antigen. Addition of recombinant IL-2 to the cultures was able to restore the proliferative capability of the cells. In further analyzing the ability of TH5.2 MAb to augment the proliferative capability of PBMC to antigen and mitogen stimulation in vitro, it was determined that TH5.2 MAb was capable of acting synergistically with antigen or mitogen in increasing the Il-2-producing capability of T cells. Taken together the data suggest that the TH5.2 determinants is involved in the proliferative capability of T cells and is functioning at the level of IL-2 synthesis and/or secretion. PMID- 3111723 TI - B cells as antigen-presenting cells: antigen-specific IL-2 production by cloned T cells without expression of IL-2 receptors. AB - A murine T cell clone, 24-2C, responds specifically to human IgG (HGG) in the context of I-Ab. B cells purified from mouse spleen cells were examined for their function as antigen-presenting cells (APC) in the response of 24-2C cells to HGG. B cells functioned as APC for IL-2 production but not for proliferation, whereas spleen cells or spleen-adherent cells functioned as APC for both IL-2 production and proliferation. LPS-activated B cells also failed to induce the proliferative response. The addition of the culture supernatant of 24-2C cells stimulated with HGG presented by irradiated spleen cells to the culture of 24-2C cells, irradiated B cells, and HGG induced the proliferative response of 24-2C cells, whereas IL-1, IL-3, and/or interferon-gamma did not reconstitute the proliferation. The expression of IL-2 receptors (IL-2R) on 24-2C cells was examined using a monoclonal anti-mouse IL-2R antibody AMT 13 or 7D4. 24-2C cells cultured with spleen cells as APC expressed IL-2R. Those cultured alone or with B cells as APC did not express IL-2R. Enlargement of 24-2C cells in response to HGG was also examined, and the relative cell size of those cultured with B cells or spleen cells as APC was larger than that of those cultured alone. These results demonstrate that B cells as APC induce IL-2 production and cell size enlargement in the response of 24-2C cloned T cells to HGG, but not IL-2R expression nor proliferation. PMID- 3111724 TI - Activation of autoreactive cytolytic T lymphocyte clone against human melanoma by anti-T3 monoclonal antibody and autologous accessory cells. AB - A cytotoxic T-lymphocyte (CTL) clone Tc1.8 was derived in a limiting dilution culture from a single cell that was derived from melanoma-involved lymph node lymphocytes activated in in vitro coculture against the autologous melanoma cells (VIP). The clone Tc1.8 (T3+, T8+, T4-, and Leu7-) expressed restricted cytolytic activity against only the autologous target VIP. As it aged in continuous culture containing interleukin 2, Tc1.8 lost cytolytic activity. The cytolytic function could be restored, however, with monoclonal antibody (MoAb) against T3 (OKT3) or with F(ab')2 fractions of OKT3, and upon restimulation with irradiated accessory cells. OKT3-mediated reinduction of cytotoxicity by the aged Tc1.8 could not be achieved if the T3 molecules were modulated from the effector cell surface following overnight incubation of Tc1.8 with saturating concentrations of OKT3 MoAb. Following reactivation with OKT3 Tc1.8 gained cytolytic function against NK targets in addition to VIP. Reactivation with F(ab')2 fractions of OKT3 and with autologous accessory cells, however, maintained its restricted antigen fidelity. The NK-like activity of Tc1.8 upon reactivation with OKT3 resulted from conjugate formation between the activated Tc1.8 and NK targets via the activating ligand itself. Thus, upon stimulation with anti-T3 MoAb and with autologous accessory cells, independently, the autoreactivity could be restored in an aged and inactive CTL clone. PMID- 3111725 TI - Ontogeny of T cells: development of pre-T cells from fetal liver and yolk sac in the thymus microenvironment. AB - The patterns of development of T cells from the very early stem cells that settle in the embryonic thymus have been studied. For this purpose, mouse embryonic thymuses (14 days) depleted of thymocytes were reconstituted with hemopoietic stem cells from fetal liver (FL) and yolk sac (YS) and T-cell development was followed in vitro in organ culture. It was found that cells derived from FL and YS of 10- to 14-day-old embryos were capable of reconstituting depleted thymic explants and exhibiting membrane markers in a pattern similar to that of thymocytes developing in intact thymic explants. Furthermore, these cells responded to concanavalin A in proliferative and cytotoxic assays as measured by limiting-dilution analysis. Thus, lymphohemopoietic stem cells emerging in the embryo prior to thymus lymphoid development are capable of differentiation in the thymus microenvironment into T cells, identified by phenotypic markers and functions that are characteristic of cells developing in the intact embryonic thymus. PMID- 3111726 TI - Role of HLA class I and class II antigens in activation and differentiation of B cells. AB - The monoclonal antibodies (MoAb) CR10-214, CR11-115, and Q1/28 to distinct monomorphic determinants of HLA class I antigens, the MoAb CL413 and PTF29.12 recognizing monomorphic determinants of HLA-DR antigens, the anti-HLA-DQw1 MoAb KS11, the anti-HLA-DPw1 MoAb B7/21, and the anti-HLA-DR,DP MoAb CR11-462 were tested for their ability to modulate human B-lymphocyte proliferation and maturation to IgM-forming cells. Purified tonsillar B cells were stimulated with Staphylococcus aureus bacteria of the Cowan first strain (SAC) or anti-human mu chain xenoantibodies, as well as in growth factor- or T-cell-dependent activation cultures. The B-cell proliferative responses induced by SAC or by mitogenic concentrations of anti-mu-chain xenoantibodies were inhibited by some of the anti HLA class I and anti-HLA class II monoclonal antibodies tested. The same antibodies were effective inhibitors of the proliferation of B cells stimulated with interferon-gamma (IFN-gamma) or interleukin-2 (IL-2) and with submitogenic concentrations of anti-mu-chain xenoantibodies. The proliferation induced by IL-2 of SAC-preactivated B cells was inhibited by some of the anti-HLA class II monoclonal antibodies, but not by the anti-HLA class I monoclonal antibodies tested. This inhibition appeared to reflect at least in part a direct effect on later events of the B-cell activation cascade, since some anti-HLA class II monoclonal antibodies still exerted considerable inhibitory activity when added together with IL-2 to SAC-preactivated B cells after the third day of culture. Anti HLA-DR, DQ, and DP monoclonal antibodies consistently inhibited the IgM production induced in B cells by T cells alone, T cells plus pokeweed mitogen (PWM), SAC plus IL-2, or IL-2 alone. In contrast, two of the three anti-HLA class I monoclonal antibodies tested inhibited the IgM production in cultures stimulated with SAC plus IL-2 and one the IgM production induced by IL-2 alone, but none of them had inhibitory effects on T-cell dependent IgM production. The results reported herein indicate that HLA class II molecules directly participate in different phases of the B-cell activation cascade. In addition, our data also suggest that HLA class I molecules can be involved in the events leading to B cell proliferation and differentiation into immunoglobulin-secreting cells. PMID- 3111727 TI - [Oxygen consumption in infants with congenital heart defects]. PMID- 3111728 TI - Chemoprophylaxis in clean-contaminated surgery. AB - Prophylaxis should be restricted to operations for which its benefit has been established. These are mainly operations in which a viscus colonized by bacteria is opened and in which bacterial contamination is unavoidable. The most important principle is to ensure adequate blood levels of antibiotic at the time of surgery. The choice of antibiotic should be based on knowledge of bacteria likely to cause infection. PMID- 3111729 TI - Chemical and pharmaceutical studies on medicinal plants in Paraguay. I. Isolation and identification of lens aldose reductase inhibitor from "tapecue," Acanthospermum australe O.K. PMID- 3111730 TI - [Eosinophilic granulomatous hepatitis. Apropos of 3 cases]. AB - The authors report three cases of eosinophilic granulomatous hepatitis observed among 325 liver puncture biopsies. The patients had urinary bilharziasis and had just been treated with oltipraz. These cases were probably due to eosinophilic reactions which sometimes follow treatment of schistosomiasis. PMID- 3111731 TI - [Method of biological control of Triatominae, vectors of Chagas disease, using entomopathogenic Hyphomycetes. Preliminary study]. AB - Bioassays determined the pathogenic activity of 14 strains of 5 entomopathogenic hyphomycetous species (Fungi imperfecti), Beauveria bassiana, Beauveria brongniartii, Metarhizium anisopliae, Nomuraea rileyi and Paecilomyces fumosoroseus to Rhodnius prolixus. Treatments consisted of direct spraying with conidial titrated suspensions on first instar larvae. When tested at 3 X 10(5) conidia/cm2, only 2 strains, B. bassiana n. 297 and B. bassiana n. 326 killed 100% of larvae at 10 days post-exposure. In the same time their LD50 and their LD90 did not differ significantly. After 3 weeks, the mortality caused by either dose of spores of B. bassiana n. 297 was very high. In contrast, in the case of B. bassiana n. 326 mortality due to reduced doses remained at low rates. This laboratory study demonstrated that the isolate, B. bassiana n. 297 might have potential as microbial control agent against the assassin bugs. PMID- 3111732 TI - [Auxotypes, plasmid content and serovars of 3 strains of Neisseria gonorrhoeae isolated in Bordeaux in 1955]. AB - Penicillinase-producing gonococci are isolated with increasing frequency. Epidemiologic markers, auxotypes, serovars, plasmids have been studied for three strains isolated in Bordeaux, responsible for therapeutic failure. For two of them, the source of contamination could be identified as endemic countries. PMID- 3111733 TI - [Current risks in the introduction of schistosomiasis into French Guiana]. AB - At the moment, it seems unlikely that there is a possibility for schistosomiasis implantation in French Guiana. The reasons to this are both the number of the immigrants infested by Schistosoma mansoni which is quite low and the disappearance of the intermediate host Biomphalaria glabrata. The disappearance of the species may be a temporary one. PMID- 3111734 TI - [Comparative study of the human basophil degranulation test and total and specific IgE levels in schistosomiasis. 54 cases]. AB - In 54 patients (45 Africans and 9 West-Indians) we searched schistosomiasis and the presence of immunoglobulins E by different tests (total immunoglobulin E levels, measurement of specific IgE, human basophil degranulation test). In patients with an excretion of living eggs we observed 91.6% of positive responses for the II. B. D. T. and 100% for the specific IgE. In cases only identified by examination of rectal mucosa biopsy specimens showing apparently living eggs, we observed 75% and 87.5% of positive responses for the same tests. But in both categories of patients, the parasitological examination is the most important. Moreover the authors observed "false-positive" and "false negative" tests compared with the parasitological results and between the tests. It suggests that the best use of these is in case of very probable schistosomiasis without positive parasitological results. PMID- 3111735 TI - [Maculopathy with golden paillettes]. PMID- 3111736 TI - The effect of changes in arterial CO2 tension on plasma lidocaine concentration. AB - The authors studied the effect of changes in arterial carbon dioxide tension on plasma lidocaine concentrations during a constant lidocaine infusion in eight healthy volunteers. With a PaCO2 of 41.4 +/- 0.9 mmHg (mean +/- SE), total plasma lidocaine concentrations were 3.97 +/- 0.20 microgram X ml-1. There was no significant change associated with hypercarbia (PaCO2 = 55.7 +/- 1.5 mmHg, lidocaine = 3.93 +/- 0.18 microgram X ml-1) or hypocarbia (PaCO2 = 19.5 +/- 1.4 mmHg, lidocaine = 4.29 +/- 0.25 microgram X ml-1), despite the known effects of changes in CO2 tension on hepatic blood flow and lidocaine protein binding. During hypercarbia, plasma lidocaine binding decreases while total plasma lidocaine remains essentially constant; therefore, increased CO2 tensions could cause toxicity if total lidocaine concentrations were in the high therapeutic range (5 micrograms X ml-1). Four subjects experienced transient symptoms of mild lidocaine toxicity during acute increases in carbon dioxide tension. PMID- 3111738 TI - Transformation related expression of glutathione-S-transferase P in rat liver cells. AB - A neutral isoenzyme of glutathione transferase designated glutathione-S transferase 7-7, but also referred to as glutathione-S-transferase P (GST-P) is absent from adult rat liver hepatocytes, but expressed at a very early stage in chemically induced in vivo hepatocarcinogenesis. The expression of this enzyme in a range of aflatoxin B1 (AFB1) associated hepatocarcinogenic systems has been examined, including in vivo induced preneoplastic and neoplastic liver tissue, cell lines derived from hepatomas, primary hepatocytes in culture and an immortalized rat liver cell line before and after transformation in vitro either by transfection with ras oncogenes or by treatment with metabolically activated AFB1. Analyses of total cytosol proteins using a polyclonal antibody to GST-P did not detect the presence of GST-P protein in cytosols from control or regenerating liver. A low level of expression was detected in the immortalized, non transformed epithelial cell line, but a greatly induced level occurred subsequent to transformation of these cells by either of the two techniques used. High levels of the protein were detected in in vivo induced preneoplastic and neoplastic tissues, and in the cell lines derived from them. Total RNA fractions isolated from the various cells or tissues, when examined with a cDNA probe for GST-P mRNA, showed it to be absent from control and regenerating rat liver. It was present at low levels in the untransformed cell line and primary hepatocytes after 48 h in culture, but present at greatest abundance in the in vivo and in vitro transformed cells. The results indicate that the highest elevation in expression of this protein is associated with the stage of definitive malignant transformation in in vitro carcinogenesis, and this could have relevance in defining comparable events in the in vivo multistage sequence. PMID- 3111737 TI - Collaborative study on antigens for immunodiagnosis of Schistosoma japonicum infection. AB - Six research laboratories in Australia, Japan, the Philippines and the USA participated in a collaborative evaluation of immunodiagnostic tests for Schistosoma japonicum infections. The serum bank consisted of 385 well-documented sera from Brazil, Kenya, Philippines, Republic of Korea and Europe. Twelve S. japonicum antigen/test system combinations were evaluated.Crude S. japonicum egg antigens showed the highest sensitivity and specificity. The defined or characterized antigens showed no advantage over the crude antigens. Quantitative seroreactivity of all S. japonicum antigens showed a positive correlation with faecal egg counts (log x + 1) in all age groups. The performance of the circumoval precipitin test was satisfactory within the same laboratory but with differences in the results between laboratories. A monoclonal antibody used in a competitive radioimmunoassay test system performed as well as the crude egg antigens.The high sensitivity of crude S. japonicum antigens now permits further evaluation for wide-scale use in public health laboratories of endemic areas to support control efforts. PMID- 3111739 TI - Isolation and characterization of the major serum albumin adduct formed by aflatoxin B1 in vivo in rats. AB - Aflatoxin B1 (AFB1) was shown to react primarily with one or more lysine residues in serum albumin (SA), accounting for more than half of the total binding to this protein. The radioactivity associated with SA following administration of [U 14C]AFB1 to rats was cleared with a half-life of 2.5 days, which is not significantly different from the half-life of unmodified albumin in the normal rat. The product isolated from a Pronase digest of in vivo-modified SA was identical by chromatographic retention time and u.v. and mass spectroscopy to the synthetic product obtained by the acylase-catalyzed deacetylation of the reaction product of N alpha-acetyl-L-lysine with 8,9-dihydro-8,9-dibromo-AFB1. The latter was characterized by u.v., fluorescence, 500 MHz 1H-n.m.r. and fast atom bombardment mass spectrometry. The spectral data strongly support a structure in which the terminal dihydrofuran ring of AFB1 has been converted to a pyrrolinone ring. It is proposed that the initial adduct is formed by condensation of the dialdehyde tautomer of 8,9-dihydro-8,9-dihydroxy-AFB1, with the epsilon-amino group of lysine, to form a Schiff base, and that the Schiff base undergoes an Amadori rearrangement to an alpha-amino ketone. The pyrrolinone ring is formed by condensation of the amino group with the remaining aldehyde to yield the final product. The purified product was relatively stable but was shown to decompose significantly under the conditions used to isolate it from modified SA. PMID- 3111740 TI - Metabolism and DNA binding of aflatoxicol and aflatoxin B1 in vivo and in isolated hepatocytes from rainbow trout (Salmo gairdneri). AB - The purpose of this study was to compare the metabolism and DNA binding of aflatoxicol (AFL) with that of aflatoxin B1 (AFB1) in vivo and in isolated hepatocytes from Mt Shasta strain rainbow trout (Salmo gairdneri). Maximum total binding of [3H]AFL to liver DNA from trout exposed by intraperitoneal injection was 38-47% of that of [3H]AFB1 over a 1-7 day period. The average AFL/AFB1 DNA binding ratio in 1-h incubations with isolated hepatocytes was 0.67 +/- 0.36 (n = 13). In freshly isolated hepatocytes, substantial interconversion between AFB1 and AFL via reductase and dehydrogenase enzymes was observed. Total in vivo excretion of conjugates in bile over 4 days was greater for [3H]AFL substrate than for [3H]AFB1. To determine if AFL binding was due to direct activation or to prior metabolism to AFB1 followed by activation, AFL with a tritium atom on the carbon containing the cyclopentenol function [1-3H]AFL, was synthesized and incubated with hepatocytes. Binding of [1-3H]AFL was 3% that of [3H]AFB1 and represents only direct binding of the intact cyclopentenol epoxide molecule before transformation to AFB1 and consequent loss of 3H. H.p.l.c. analysis of DNA hydrolyzed after incubation with [1-3H]AFL resulted primarily in production of non-radioactive 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7 guanine). A radioactive peak estimated to be 1% as abundant as the AFB1-N7 guanine was also observed. The overall binding of generally labeled [3H]AFL to trout liver DNA in vivo and in freshly prepared hepatocytes correlates well with available tumor incidence and mutagenicity data. Conclusions from these findings are that direct interaction of AFL-8,9-epoxide with DNA is of relatively minor quantitative importance in rainbow trout hepatocytes and that the major adduct results from conversion of AFL to AFB1 prior to epoxide formation. PMID- 3111741 TI - The response to DNA damage induced by 4-nitroquinoline-1-oxide or its 3-methyl derivative in xeroderma pigmentosum fibroblasts belonging to different complementation groups: evidence for different epistasis groups involved in the repair of large adducts in human DNA. AB - The data in this paper show that when the inhibition of growth is measured, xeroderma pigmentosum (XP) complementation groups A, G and D are very sensitive to 4-nitroquinoline-1-oxide (4NQO), whereas only XP groups G and D are very sensitive to 3-methyl-4NQO (3me4NQO). Cells belonging to XP-C group are not particularly sensitive to either agent. Thus there are different epistasis groups for the excision repair of DNA adducts induced by these agents as opposed to the repair of u.v. damage. DNA polymerase alpha is involved in the repair of 4NQO induced lesions because aphidicolin blocks their repair. XP cells from all the above groups are defective to some extent in this repair. The degree of repair defectiveness follows that seen after u.v., with even the XP-C cell line used having reduced repair (despite the fact that the inhibition of growth by 4NQO in this cell line was not markedly different from normal). Aphidicolin did not induce breaks in the normal or XP cell lines exposed to 3me4NQO, thus the repair of lesions induced by 3me4NQO does not involve DNA polymerase alpha in any of the cell lines. Finally, catalase reduces the alkaline labile lesions induced by 4NQO, but not 3me4NQO, suggesting the latter agent does not induce substantial amounts of DNA damage by the generation of radicals. PMID- 3111742 TI - Induction of sister chromatid exchanges in cultured adult rat hepatocytes by directly and indirectly acting mutagens/carcinogens. AB - Primary cultures of adult rat hepatocytes were tested for their suitability to assess sister chromatid exchange (SCE)-inducing DNA damage produced by both directly and indirectly acting mutagens/carcinogens. Compared to other genotoxicity assay systems which utilize the metabolizing activity of liver microsomes, this system is at least 1-2 orders of magnitude more sensitive. The approximate drug concentrations leading to a doubling of control SCE levels were 2.5 X 10(-4) M for cyclophosphamide, 4.5 X 10(-5) M for dimethylnitrosamine, 2.5 X 10(-6) M for N-methyl-N-nitro-N-nitrosoguanidine, 2 X 10(-10) M for aflatoxin B1 (AFB1) and 30 mJ for u.v. The most potent inducer of SCE proved to be AFB1, leading to a significantly elevated level of exchanges at a concentration of 10( 12) M. The increased background SCE levels observed (0.75 SCE/chromosome) appears to reflect the sensitivity of hepatocytes to SCE-inducing DNA damage resulting from the dietary intake of mutagenic/carcinogenic compounds. In view of the high sensitivity and versatility of this genotoxicity assay system, it will be of use for the detection of the low levels of mutagenic/carcinogenic compounds found in the environment. PMID- 3111743 TI - Comparison of single and multiple doses of prophylactic antibiotics in experimental streptococcal endocarditis. AB - Single-doses or short-term administration of beta-lactam antibiotics alone or combined with aminoglucoside antibiotics have failed to consistently prevent experimental streptococcal endocarditis induced by high inocula of bacteria poorly susceptible to killing by these antibiotics. The optimal duration of administration of antibiotics for successful prophylaxis under these circumstances has not been established. We therefore tested, in rats with catheter-induced sterile aortic vegetations, the duration of administration of antibiotic necessary to prevent endocarditis induced by bacterial inocula 100 to 10,000 times the 90% infective dose of two tolerant viridans-group streptococci and two Streptococcus faecalis strains. Multiple-dose regimens of amoxicillin alone or of amoxicillin combined with gentamicin were studied. Against the two viridans group streptococci, successful prophylaxis was achieved with multiple doses of amoxicillin alone given over 24 to 48 hr and by the combination of amoxicillin and gentamicin given for 6 to 24 hr. Against the two S. faecalis strains, multiple-dose regimens with amoxicillin alone failed, but the combination of amoxicillin and gentamicin was successful when administered for 48 to 72 hr. Thus, after challenge with high bacterial inocula, repeated doses of a beta-lactam antibiotic alone were sufficient to prevent viridans streptococcal endocarditis, but multiple doses of a bactericidal combination (beta-lactam plus aminoglucoside), as necessary for the treatment of established endocarditis, were a prerequisite for successful prophylaxis of S. faecalis endocarditis. PMID- 3111744 TI - Attenuation of dysfunction in the postischemic 'stunned' myocardium by dimethylthiourea. AB - The mechanism for the prolonged contractile dysfunction observed in myocardium reperfused after reversible regional ischemia ("stunned" myocardium) is unclear. Recent studies suggest that myocardial stunning may be mediated by oxygen-derived free radicals, but the precise molecular species involved remain unknown. Thus we explored the role of the highly cytotoxic hydroxyl radical in regional postischemic dysfunction by using dimethylthiourea (DMTU), an effective and highly permeable hydroxyl radical scavenger. Open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery followed by 4 hr of reperfusion received either DMTU (0.5 g/kg iv over 45 min starting 30 min before occlusion, n = 14) or saline (n = 15). Control and treated dogs were comparable with respect to variables that may affect postischemic dysfunction, including heart rate, aortic pressure, left atrial pressure, arterial blood gases and hemoglobin concentration, size of the occluded bed (determined by postmortem perfusion), and collateral blood flow (determined by radioactive microspheres). Regional myocardial function was assessed by measuring wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesis during ischemia. After reperfusion, however, wall thickening (expressed as percent of baseline) was considerably greater in treated as compared with control dogs: 53 +/- 9% (mean +/- SEM) vs 9 +/- 14% (p less than .03) at 1 hr, 55 +/- 9% vs 23 +/- 13% (p less than .05) at 2 hr, 60 +/- 9% vs 28 +/- 14% (p less than .05) at 3 hr, and 67 +/- 5% vs 36 +/- 13% (p less than .05) at 4 hr. Thus DMTU produced a significant and sustained improvement in recovery of contractile function. In concentrations greater than the plasma levels attained in vivo, DMTU did not scavenge either hydrogen peroxide or superoxide anion in vitro. These results suggest that the myocardial dysfunction occurring after a brief episode of regional ischemia is mediated in part by the hydroxyl radical. PMID- 3111745 TI - New thrombolytic drugs in acute myocardial infarction: theoretical and practical considerations. PMID- 3111746 TI - Pharmacologic thrombolysis: tissue-type plasminogen activator. PMID- 3111749 TI - Concentrations of iodothyronines in serum of patients with chronic renal failure and other nonthyroidal illnesses: role of free fatty acids. AB - The mean concentration of free thyroxin (FT4) in serum, as determined by direct equilibrium dialysis, was decreased in patients with chronic renal failure (CRF) and increased in patients with various other nonthyroidal illnesses (NTI). The mean concentration of dialyzable free triiodothyronine (FT3) in serum was equally low in both groups of patients. Patients with CRF of various etiology but a similar degree of renal failure as estimated from serum creatinine assay had very similar concentrations of FT4 and FT3 in their serum. Mean thyroxin (T4) and triiodothyronine (T3) concentrations in serum were decreased in CRF and NTI, whereas the mean reverse-T3 concentration in serum was normal in CRF and increased in NTI. T4-binding globulin and albumin were markedly decreased in CRF and NTI; T4-binding prealbumin was increased in CRF and decreased in NTI. The mean concentration of nonesterified free fatty acids (FFA) in serum was increased in NTI but not in CRF. The weak, but significant, positive correlation observed between FT4 and FFA in serum (r = 0.34, P less than 0.01) in NTI indicates that the increase in serum FT4 in this group of patients could be an effect, at least in part, of FFA competing with T4 for binding sites on serum proteins. The stronger correlation detected between the serum FT4 concentration and the FFA/albumin molar ratio in serum (r = 0.60, P less than 0.001) demonstrates the importance of a low albumin concentration for expression of the effect of FFA on FT4 in severe systemic illnesses. PMID- 3111748 TI - Gold myokymia syndrome. A rare toxic manifestation of chrysotherapy. PMID- 3111747 TI - Rapid regression of hepatic focal fatty infiltration. Computed-tomographic and ultrasound correlation. PMID- 3111750 TI - Biological variation of blood acid-base status: consequences for analytical goal setting and interpretation of results. AB - Analytical, intra-individual, and interindividual components of variation have been determined for pH, pCO2, bicarbonate, base excess, and total CO2 in capillary specimens of whole blood from a cohort of 14 healthy subjects. Calculated analytical goals (SD) are pH less than or equal to 0.008, pCO2 less than or equal to 0.9 mmHg, bicarbonate less than or equal to 0.5 mmol/L, base excess less than or equal to 0.5 mmol/L, and total CO2 less than or equal to 0.5 mmol/L. Because pH and base excess vary little between individuals, population based reference values for them will be of utility in interpretation of results; pCO2, bicarbonate, and total CO2 show more marked variation between individuals, and reference values for them will be of more limited use. The generally applicable differences required for two results to be significantly different (P less than or equal to 0.05) when goals are met--which is currently feasible--are pH: 0.04, pCO2: 0.745 kPa (5.6 mmHg), bicarbonate: 2.6 mmol/L, base excess: 2.2 mmol/L, and total CO2: 2.7 mmol/L. PMID- 3111752 TI - Rapid typing of serum paraproteins by immunoblotting without antigen-excess artifacts. AB - In this new immunoblotting procedure for determining the heavy-chain class and light-chain type of monoclonal serum immunoglobulins, proteins are transferred from agarose electrophoretic gels to nitrocellulose by brief capillary blotting. Paraproteins transferred are detected with appropriate horseradish peroxidase conjugated antisera to light chain and heavy chain. Examination of 121 serum specimens probably containing a paraprotein (as detected by protein staining) by immunoblotting and by immunofixation gave the same results for 116 specimens: paraproteins were typed in 103 specimens and their presence was excluded in 13. Immunoblotting required one repeat analysis (as compared with 22 for immunofixation). In only 100 min we could type as many as 10 paraproteins, and the procedure did not show antigen-excess artifacts. These results suggest that immunoblotting may be preferable to immunofixation for routine typing of paraproteins. PMID- 3111753 TI - Technical and clinical performance of six sensitive immunoradiometric assays of thyrotropin in serum. AB - We evaluated the analytical and clinical performance of six commercial immunoradiometric assay kits for thyrotropin (TSH) in serum in 218 subjects, with and without thyroid dysfunction. Detection limits of the six kits were lower (from 0.07 to 0.25 milli-int. unit/L) than that of conventional TSH RIA (0.7 milli-int. unit/L). Precision was adequate over a wide range of concentrations, although interassay CVs at very low concentrations were good for only two kits (7.3% and 13.1%). Results by all the kits correlated to about the same degree with the TSH RIA (r = 0.92 to 0.98). All showed a positive correlation between both the basal and post-thyroliberin (TRH)-stimulation values for TSH (r = 0.78 to 0.88), and all showed similar euthyroid reference ranges for basal concentrations of TSH. With four of the six kits we could clearly distinguish most of the hyperthyroid patients from healthy euthyroids; however, basal and post-TRH TSH values were not sufficient to discriminate among groups of patients with different grades of thyroid hyperfunction. PMID- 3111751 TI - Three immunoassay methods evaluated for quantifying prealbumin (transthyretin) in serum. AB - We developed an immunoturbidimetric assay for prealbumin on the Cobas Bio centrifugal analyzer and compared results from this assay with those from a rate nephelometric assay (Beckman Instruments Inc.) and a radial immunodiffusion kit (Behring Diagnostics). All three assays were evaluated for precision, linearity, and correlation to each other for analysis of sera from pediatric patients. All assays gave similar results for patients' samples. Values were higher by the radial immunodiffusion assay than by the other two methods, which gave similar results for the same specimens. We conclude that the immunoturbidimetric and rate nephelometric assay for prealbumin are acceptable alternatives for quantifying prealbumin in serum and also have a faster turnaround time than radial immunodiffusion. PMID- 3111754 TI - Thyroid function in hospitalized patients: effect of illness and serum albumin concentrations. AB - We assessed the clinical utility of measuring thyrotropin (TSH) in serum by immunoradiometry and of measuring total thyroxin (TT4), total triiodothyronine (TT3), free thyroxin (FT4), and free triiodothyronine (FT3). We used a group of 110 healthy volunteers, 45 ill hypoalbuminemic patients, and 42 ill normoalbuminemic patients. In addition, the free thyroxin index (FTI) and TT4:thyroxin-binding globulin (TBG) ratio were also calculated. The hypoalbuminemic group had significantly lower FT4, FT3, TT4, TT3, and FTI concentrations, but only FT3 and TT3 were significantly lower in the ill normoalbuminemic group as compared with controls. We found significant correlation between FT4 and albumin (r = 0.372, P less than 0.001) and FT3 and albumin (r = 0.465, P less than 0.001). TSH concentrations were undetectable in two of 45 hypoalbuminemic patients, significantly higher in the rest. The TT4/TBG ratio was the only parameter of thyroid function that remained unchanged in the ill patients. PMID- 3111755 TI - Bimodal distribution in venous carbon dioxide content in healthy subjects. PMID- 3111756 TI - A lactate dehydrogenase-immunoglobulin G1 complex, not blocked by anti-idiotype antibody, in a patient with IgG1-lambda type M-proteinemia. AB - The serum of a patient with IgG1-lambda type M-proteinemia showed an abnormal isoenzyme pattern for lactate dehydrogenase (LDH, EC 1.1.1.27). By affinity chromatography, we showed that four isoenzymes (LDH2, LDH3, LDH4, and LDH5) were bound to the M-protein. This complex formation was not blocked by anti-idiotype antibody, even though the binding capacity of IgG was exclusively located in the Fab region of the molecule. Moreover, heavy and light chains of the patient's IgG, obtained by reduction, separately had affinities for each of the LDH isoenzymes. LDH-IgG complex was easily dissociated by affinity chromatography on 5'-AMP-Sepharose 4B or by added NADH. We propose the following hypothesis for the LDH-IgG complex formation: LDH can recognize the gamma-Fab region of IgG at the NAD+ binding site of the molecule, but the affinity of the LDH molecule for immunoglobulin is much weaker than that for NADH or 5'-AMP. PMID- 3111757 TI - Fatty acid composition of phospholipids in bile in man: promoting effect of deoxycholate on arachidonate. AB - Ninety-five percent of phospholipids (PLs) in bile is secreted as phosphatidylcholine or lecithin. The study of fatty acid patterns of phospholipids present in gallbladder bile could help clarify whether a preponderance of certain fatty acids could play a role in cholesterol gallstone formation in man. In acute bile acid-exchange experiments, it was found that more hydrophobic bile acids did promote the excretion in bile of PL rich in arachidonic acid (a prostaglandin precursor) and stearic acid. We studied, therefore, bile acid, cholesterol and phospholipid fatty acid patterns (measured by gas chromatography) in gallbladder bile, obtained by duodenal intubation and cholecystokinin-stimulation of 24 healthy volunteers with normal liver/gallbladder function (ultrasound). PL-fatty acid composition (mean % +/- SD) was 41.40 (+/- 1.41) for palmitic acid, 2.68 (+/- 0.82) for palmitoleic acid, 5.50 (+/- 1.55) for stearic acid, 12.09 (+/- 0.98) for oleic acid, 32.83 (+/- 3.04) for linoleic acid and 5.64 (+/- 1.59) for arachidonic acid. The proportion of biliary deoxycholate was positively correlated with arachidonic acid (r = 0.71; p less than 0.01), whereas chenodeoxycholate was inversely correlated with arachidonic acid (r = -0.53; p less than 0.01). There was a positive correlation between biliary chenodeoxycholate and linoleic acid (r = 0.48; p less than 0.05) and a negative correlation between biliary deoxycholate and linoleic acid composition (r = 0.68; p less than 0.01). Also a correlation was found between palmitic acid and cholesterol saturation index (r = 0.49; p less than 0.05). We conclude that the hydrophobic bile acid deoxycholate, which does not desaturate cholesterol in bile, promotes the biliary excretion of arachidonic acid. Since arachidonic acid could induce the gallbladder mucosa to produce prostaglandins and mucus, increased biliary PL-arachidonic acid composition might be a factor in cholesterol gallstone disease. PMID- 3111758 TI - Effect of angiotensin converting enzyme inhibitor (captopril) on cerebral blood flow in hypertensive patients without a history of stroke. AB - The effect of the angiotensin converting enzyme inhibitor, captopril, on cerebral blood flow (CBF) was studied in 11 hypertensives without a history of stroke. Mean hemispheric CBF (mCBF) was measured in each patient by Xe-133 inhalation method before and after 7 days of captopril administration. Blood pressure (BP) both in the control state and at the time of CBF measurement decreased significantly after drug administration. mCBF, however, did not show any significant change. When percent changes in mCBF before and after the administration were plotted against those of mean arterial BP, significant inverse correlations were obtained in both hemispheres; the larger the BP decrease, the more increase in CBF was observed. It is concluded that captopril lowers systemic BP without concomitant decrease in CBF in hypertensive subjects with no history of stroke. Furthermore, the results suggest that captopril may have a vasodilating action on cerebral blood vessels. PMID- 3111759 TI - Microbicidal activity of monocyte derived macrophages in AIDS and related disorders. AB - We have examined the ability of monocyte-derived macrophages from patients with AIDS and other HIV-related disorders to kill the intracellular pathogen Toxoplasma gondii. We have also examined the capacity of peripheral blood mononuclear cells from these patients to produce macrophage-activating and other lymphokines. The capacity to produce interleukin 2 and gamma interferon decreases from controls through asymptomatic seropositive subjects and lymphadenopathy groups A (benign) and B (prodromal) to AIDS. The decrease did not correlate precisely with the decrease in CD4+ cells in these patients. Monocyte-derived macrophages from asymptomatic HIV-infected subjects and lymphadenopathy patients showed a decreased ability to kill T. gondii after activation with recombinant gamma interferon; paradoxically, this was most striking for PGL group A. The defect was largely overcome by using Concanavalin A stimulated autologous supernatants. It was notable that macrophages from AIDS patients showed normal killing with recombinant gamma interferon, but that the supernatants from AIDS patients had reduced activity with normal macrophages. These studies confirm that functional defects of both lymphocytes and macrophages are found in HIV-infected subjects; they serve to emphasize the heterogeneity of the clinical and biological responses to this retrovirus, responses which have important implications in the pathogenesis and treatment of the immunodeficiency. PMID- 3111760 TI - Immunity to schistosomiasis mansoni in guinea-pigs vaccinated with radiation attenuated cercariae: I. Humoral responses against skin-stage schistosomula. AB - The anti-schistosomular humoral responses of guinea-pigs vaccinated with radiation-attenuated cercariae of Schistosoma mansoni have been investigated in vitro. The sera of vaccinated animals contain schistosomulicidal complement fixing antibodies which peak in titre at week 5 after vaccination and predominantly consist of IgG2 and IgM antibodies. The ability of the serum to arm macrophages from normal animals to bind to schistosomula, also peaks in titre at week 5 and is associated with IgG2 antibodies. Basophils from normal animals can be sensitized in vitro by vaccine serum to degranulate in the presence of schistosomular antigens. This anaphylactic antibody activity is associated with IgG1 but not IgE antibodies, and peaks in titre at week 10. Three antigens (14 kD, 20 kD and 43 kD) are specifically and transiently detected by vaccine serum on Western blots of schistosomular proteins; these antigens are first discernible at week 4, but were virtually undetectable at week 12. PMID- 3111761 TI - Immunological studies on Kawasaki disease: II. Isolation and characterization of an immunosuppressive factor in acute phase sera. AB - Acute phase serum from a patient with Kawasaki disease possessed strong inhibitory activity for the proliferative response of Con A-stimulated peripheral blood mononuclear cells. The inhibitor was fractionated step-wise by means of DEAE-Sephadex A-50 ion exchange chromatography followed by Sephadex G-100 gel filtration and high performance liquid chromatography. A major protein of 140 kD with 2000 times greater inhibitory activity than the original serum was identified in the final fraction. Immunization of mice with this fraction resulted in the production of three hybridoma clones secreting monoclonal antibodies (MoAb) of IgG1 class which blocked the inhibitory activity of the fraction. Two of these MoAb recognized the same epitope of the inhibitory factor, while the remaining MoAb was directed to a different epitope. Western blot analysis of acute phase sera by the MoAb demonstrated the presence of 140 kD molecules in 43 of 55 patients. PMID- 3111762 TI - Mononuclear phagocyte system Fc-receptor function in patients with seropositive rheumatoid arthritis. AB - Mononuclear phagocyte system (MPS) Fc-receptor function in 20 patients with seropositive rheumatoid arthritis (RA) was investigated using radiolabelled autologous erythrocytes coated with an average of 5,800 molecules of anti-rhesus IgG (E. IgG). Although clearance times (T1/2) of E. IgG tended to be longer in RA patients than those in healthy controls (46 +/- 6 min vs 38 +/- 5 min, mean +/- s.e.m., P = 0.38), this did not reach statistical significance. Liver spleen uptake ratios (LS ratios) were increased in patients with RA (13/100 +/- 1/100 vs 7/100 +/- 1/100, P less than 0.05). There was no correlation of T1/2 or LS ratios with articular disease activity, vasculitis, ESR, IgM containing immune complex levels or Clq-binding immune complex levels. Although Clq-binding immune complex levels were significantly higher in patients with vasculitis than in those without (P less than 0.01), T1/2 and LS ratios did not differ in these two groups of patients. The T1/2 and LS ratios of E.IgG did not reveal a defect in MPS Fc receptor function and did not correlate with one of the above-mentioned clinical and immunological parameters. We suggest that in order to establish a possible defect in Fc-receptor function correlating with disease activity and immune complex levels in RA patients, soluble immune complexes or immune complex-like material should be used as probes. PMID- 3111763 TI - IgG subclass distribution of anti-Rh, anti-Kell and anti-Duffy antibodies measured by sensitive haemagglutination assays. AB - The IgG subclass distribution of anti Rh antibodies (anti-D, 'anti-Du', anti-c, anti-E), anti-Kell and anti-Duffy (anti-Fya) antibodies was measured by two haemagglutination techniques on microtitre plates. The first technique involved rabbit subclass specific antisera which were used to agglutinate red cells previously reacted with the patients' antibodies at high concentration. The second, which was more sensitive, had an additional step by introducing sheep anti-rabbit antibodies (sandwich technique). By the sensitive sandwich technique we revealed, for anti-D antibodies: IgG1 8/19, IgG3 1/19, IgG1/IgG3 8/19, IgG1/IgG2/IgG3/IgG 41/19, IgG1/IgG4 1/19; for the Du reactive anti-D antibodies: IgG1 1/8, IgG1/IgG3 1/8, IgG1/IgG3/IgG4 6/8; for the anti-E antibodies: IgG1/IgG2/IgG4 2/3, IgG1/IgG2/IgG3/IgG4 1/3; for the anti-c antibodies: IgG1 2/5, IgG3 1/5, IgG1/IgG3 1/5; for the anti-Kell antibodies: IgG1 9/20, IgG1/IgG3 1/20, IgG1/IgG4 8/20, IgG1/IgG3/IgG4 2/20; and for anti-Duffy antibodies: IgG1 1/8, IgG1/IgG4 7/8. These results are partly at variance with previously published results. PMID- 3111764 TI - Clinical and immunological findings in four infants with Omenn's syndrome: a form of severe combined immunodeficiency with phenotypically normal T cells, elevated IgE, and eosinophilia. AB - We report four cases of Omenn's syndrome (OS), an autosomal recessive disease characterized by early erythrodermia, protracted diarrhea, severe infections, lymphadenopathy, hepatosplenomegaly, failure to thrive, and leukocytosis with marked eosinophilia. The immunological investigations revealed B lymphopenia with increased levels of serum IgE and marked depression of T-cell activation, not restored by the addition of exogenous interleukin 2 (IL-2). IL-2 and interferon gamma (IFN-gamma) production in vitro were very low or absent. One patient was treated with HLA-identical bone marrow transplant with a complete remission of the clinical picture and the immunological defect. The infant died of graft versus host disease 4 months after the graft. For the remaining three infants the outcome was also fatal within the first year of life. In conclusion, OS should be considered a severe combined immunodeficiency disease with peculiar clinical, immunological, and histological findings. PMID- 3111765 TI - In vitro and in vivo evidence that autoimmune reactivity to collagen develops spontaneously in Schistosoma mansoni-infected mice. AB - Egg-induced granuloma formation in murine schistosomiasis mansoni results from vigorous anti-parasite reaction by activated T cells, macrophages, eosinophils, and fibroblasts. The present study suggests that strain-specific, autoimmune T cell reactivity directed against host matrix proteins might also contribute to granulomatous hypersensitivity. T cells from infected C57B1/6, but not from CBA or BALB/c mice, proliferative in vitro in response to denatured collagen. T cells from uninfected mice, previously immunized with soluble egg antigen (SEA), did not respond in vitro to collagen. Spleen cells from acutely infected mice, but not chronically infected or uninfected animals, formed granulomas around collagen coupled polyacrylamide beads in vitro. This response was blocked by anti-collagen antibodies that had no inhibitory effect on in vitro granuloma formation around SEA-coupled beads. In related in vivo studies, granuloma formation was quantitated after iv injection of SEA-, collagen-, or uncoated beads into normal or infected recipients. The mean diameter of lung granulomas induced by collagen coupled beads in infected mice was significantly greater than the diameter of granulomas around either collagen beads in uninfected mice or uncoated beads in infected mice. these observations indicate that anti-collagen responses develop spontaneously in Schistosoma-infected mice and suggest that such reactivity might play a secondary role in granuloma formation and the pathogenesis of hepatic fibrosis. PMID- 3111766 TI - T-cell activation defect in common variable immunodeficiency: restoration by phorbol myristate acetate (PMA) or allogeneic macrophages. AB - Common variable immunodeficiency (CVI) represents a group of familial and sporadic diseases characterized by a range of B-cell, T-cell, and macrophage defects. A defect in T-cell activation, involving reduced proliferation and IL-2 production after stimulation with OKT3 antibody, has been described previously. In the present study we found that these defects could be corrected in vitro by adding phorbol myristate acetate (PMA) to OKT3-stimulated peripheral blood mononuclear cells (PBMC) of 14 patients with CVI. PBMC of 6 out of 7 patients with CVI studied also exhibited a profound defect in IL-2 receptor expression when incubated with OKT3 antibody. IL-2 receptor expression after stimulation with PMA alone was normal, indicating that the OKT3- but not the PMA-induced pathway of IL-2 receptor expression was defective. On the RNA level, the genes for IL-2 and IL-2 receptor were expressed after stimulation with OKT3 antibody. IL-2 and IL-2 receptor gene expression were normal, indicating a possible post transcriptional defect. To investigate whether the defect in T-cell activation was at the macrophage or the T-cell level, we prepared adherent cells and monocyte-depleted T cells (E+) from 3 patients with CVI and from normal blood donors. Incubating CVI E+ cells with normal adherent cells resulted in normal proliferation and IL-2 production in the presence of OKT3, whereas incubation of normal E+ cells with adherent cells from patients with CVI under the same conditions showed reduced IL-2 production and proliferation, suggesting the macrophage as the origin of the failure in T-cell activation in the patients with CVI studied. Inhibition by macrophage-secreted prostaglandins was excluded by failure to correct the IL-2 production and proliferation defects in the presence of indomethacin. PMID- 3111767 TI - Effects of immunoglobulin G from patients with systemic lupus erythematosus on human B cell function. AB - We examined the effect of systemic lupus erythematous (SLE) sera and Ig fractions on IgG and IgM release by cultured normal peripheral blood mononuclear cells (PBMC) when these cells were preincubated with serum dilutions or Ig fractions. Increases in both IgM and IgG (P less than 0.001 and less than 0.01) in cultured cell supernatants were recorded when PBMC were preincubated with SLE serum dilutions. IgG but not IgM from SLE was found to stimulate PBMC to release IgG (P less than 0.01). Similar results were obtained when SLE IgG was preincubated with adherent cell depleted cells (ADC) or isolated normal B cell fractions. When normal PBMC were preincubated with SLE serum or IgG and subsequently stimulated with pokeweed mitogen (PWM), a relatively blunted IgG release was observed (P less than 0.05); however, IgM release was significantly increased (P less than 0.001). This effect was not observed when PBMC were preincubated with SLE IgM, normal serum dilutions, or normal Ig fractions. Relative blunting of PWM response after PBMC were preincubated with SLE IgG was not reversed in PBMC depleted of adherent cells, OKT8+, or OKT9+ cells. Depletion of PBMC of LeuM1 cells increased IgG release in response to PWM when cells had been preincubated with SLE IgG. SLE serum or Ig fractions did not induce B cell growth factor release by T cells. SLE IgG appeared to act directly on B cell enriched populations to release IgG; this was not associated with significant increase in thymidine uptake, or apparent lysis of cells. PMID- 3111769 TI - Immunologic disease and fetal death. AB - Both maternal isoimmunization and maternal autoimmune disease are associated with fetal death. For isoimmunization the immunologic nature of fetal death (hydrops fetalis) is beyond question, but many of the details are poorly understood. It would be extremely helpful to know what immunologic factors are responsible for the wide variation in the degree of fetal hemolysis. This information would surely lead to improved management of isoimmunized pregnancies and create new and more successful therapies for fetuses at risk for hemolysis. The immunology of autoimmune-associated fetal death is, for the most part, an enigma. For the fetal deaths associated with SLE and the antiphospholipid antibodies, demise appears to be a consequence of uteroplacental vascular damage. But the observable pathology is nonspecific, and the evidence for a direct immunologic mechanism is sparse. The similarity between the uteroplacental vascular lesions found with these autoimmune conditions and those seen in preeclampsia demands more intensive investigation. For the fetal deaths caused by complete congenital heart block associated with maternal autoantibodies, the evidence for a direct immunologic mechanism is now being established. As with isoimmunization, a more complete understanding of autoimmune-associated fetal death will open new avenues of management and therapy. PMID- 3111768 TI - Requirement for mitogen, T cell-accessory cell contact, and interleukin 1 in the induction of resting T-cell proliferation. AB - The role of interleukin 1 (IL-1) and accessory cells (AC) in mitogen-driven, resting human peripheral blood T lymphocyte proliferation was examined utilizing highly purified T-cell preparations. Such preparations fail to respond to optimal concentrations of the lectin phytohemagglutin (PHA) or interleukin 2 (IL-2), indicating the functional depletion of monocytes (Mo.) and of activated T cells, respectively. The requirement for Mo. and IL-1 was quantitatively determined by adding known loads of Mo. and of recombinant human IL-1 alpha or beta forms (r hIL-1, alpha/beta) to T-cell preparations and monitoring the resultant proliferative responses to the mitogens PHA, concanavalin A (Con A), the anti-CD3 monoclonal antibody (mAb) Leu 4, and Sepharose beads-linked Leu 4. Although some mitogens induced IL-2r gene transcription and surface expression in T cells, all mitogens tested failed to drive T cells to proliferate in the absence of Mo. r-h IL-1, as well as Mo.-conditioned media, failed to support the proliferation of mitogen-treated T cells. However, r-h IL-1 significantly amplified the proliferative responses of mitogen-treated T cells when suboptimal loads of Mo. were added. Both r-h IL-1 alpha and beta forms behaved identically in all the aforementioned experiments. The necessity of T cell-Mo. contact for T-cell proliferation was established by demonstrating that T cells separated from Mo. by a semipermeable membrane which allowed free diffusion macromolecules failed to proliferate to the mitogens tested. In contrast to lectins and anti-CD3 mAb phorbol-12-myristate-13-acetate (PMA) induced on its own a modest proliferative response which was greatly enhanced by r-h IL-1 independent of the addition of monocytes. The mechanism of r-h IL-1 action in supporting PMA-primed, T-cell proliferation involved the induction of IL-2 synthesis. We conclude that IL-1 does not substitute for the need for Mo. in supporting mitogen-driven T-cell proliferation. Mitogens, direct accessory-T-cell contact, and IL-1 each act, in this order, to bring about resting T-cell proliferation. The distinct behavior of PMA might relate to its ability to substitute for monocyte contact in promoting the progress of T cells through the cell cycle. PMID- 3111770 TI - Pathologic Malgaigne fracture following pelvic irradiation. A case report. AB - A 48-year-old woman developed symptomatic superior and inferior pubic rami fractures with a concomitant subluxation of the ipsilateral sacroiliac joint three years after pelvic irradiation for a gynecologic malignancy. Pathologic pelvic fractures (PPF) caused by irradiation may be difficult to distinguish from those caused by metastatic disease. PPF produce prolonged disability. PMID- 3111771 TI - [A case of neurofibromatosis associated with Parkinson disease showing myokymia like movement and hypertrophy of the lower extremities]. PMID- 3111772 TI - [Clinical effects of oral L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in patients with Shy-Drager syndrome]. PMID- 3111773 TI - Effect of diet on islet cell transplantation. AB - Transplantation of adequate numbers of islets can normalize the clinical parameters during normal chow feeding and modified diets of cholesterol, carbohydrate and protein. The transplantation of 3,000 fresh islets gives a clinical response that is the same as the normal controls. Animals transplanted with insufficient number of islets are unable to tolerate dietary stress, which eventually exhausts the beta cells, so that insufficient insulin is secreted to normalize the transplanted animals. Diabetic animals are unable to tolerate diet modification with many of the animals dying during or shortly after the diet's modification. PMID- 3111775 TI - DRG's for physicians. PMID- 3111774 TI - Blood fuel metabolites in asthma during and after progressive submaximal exercise. AB - Ten male stable asthmatic subjects and 10 matched control subjects performed a progressive exercise test on a treadmill to 85% of their predicted maximum heart rate. Blood lactate, pyruvate, hydrogen ion, glucose, alanine, glycerol and total ketone body concentrations were measured at frequent intervals during and up to 60 min after exercise. Carbon dioxide production, oxygen consumption, ventilation, respiratory exchange ratio and oxygen saturation were also measured during and up to 10 min after exercise. There were no significant differences between the asthmatic and control subjects in levels of carbon dioxide production, oxygen consumption and ventilation. The respiratory exchange ratio was greater in the asthmatic subjects during recovery from exercise (P less than 0.05). No changes in oxygen saturation were observed during exercise in either group. In both asthmatic and control subjects, lactate, pyruvate, hydrogen ion, alanine and glycerol concentrations showed an increase from baseline levels, reaching maximum levels up to 10 min after exercise and returning to baseline within 1 h after exercise. Total ketone body concentrations decreased during exercise. There were no significant differences between the asthmatic and control subjects in the concentration of any metabolite over the study period. These data indicate that fuel metabolism during and after short-term progressive exercise is similar in stable asthmatic and normal subjects. PMID- 3111777 TI - Domiciliary consultations--necessary service or anachronistic luxury? PMID- 3111776 TI - Effect of polyanions on fibrillogenesis by type XI collagen. AB - Type XI collagen (1 alpha,2 alpha,3 alpha) from bovine articular cartilage form fibrils at 4 degrees C in 0.15 M NaCl at pH 7.4, but fibrillogenesis is inhibited by the addition of 1 M glucose or by raising the NaCl concentration to 1 M. Removal of the glucose or NaCl by dialysis allows fibril formation. When proteoglycans, heparin, or chondroitin sulfate were added to type XI collagen in 1 M NaCl both fibrillogenesis and polyanion-collagen interaction were inhibited by the high NaCl concentration. When the mixture was dialysed against 0.15 M NaCl, a new aggregate type was seen, scattered among shortened and branched fibers. The new aggregates were either X-, Y-, or wheel-shaped structures with electron dense cores. They were apparently formed by collagen molecules intersecting approximately 200 nm from one end. In contrast, when the polyanion was mixed with the collagen in 1 M glucose, which inhibits fibrillogenesis but not polyanion-collagen interaction, a different type of aggregate appeared following dialysis. These aggregates were discrete 280 X 40 nm structures with an asymmetric banding pattern. They are similar to SLS aggregates, and probably are composed of collagen molecules lined up in register. The results are different from those seen with the interstitial collagens and emphasize the unique character of the interaction of polyanions, including proteoglycan, with type XI collagen. PMID- 3111778 TI - The acute phase response to inflammation: the role of monokines in changes in liver glycoproteins and enzymes of glycoprotein metabolism. AB - The role of monocyte derived factors in the acute phase response to inflammation is discussed. The kinetics of response of alpha 1-acid glycoprotein, sialyltransferase and albumin to a rat monokine preparation is described. There was an increase in synthesis of alpha 1-acid glycoprotein and sialyltransferase and a decrease in albumin synthesis following administration. However, the kinetics of response of sialyltransferase to the monokine was much slower than was found for the other two proteins. The possibility that sialyltransferase responds to a different monokine compared to the other acute phase proteins is discussed. PMID- 3111779 TI - Studies of the egg proteins of tropical lizards: purification and partial characterization of yolk proteins of Anolis pulchellus. AB - An easy biochemical procedure for the isolation of lizard lipoprotein is presented as well as the partial characterization of several egg proteins from tropical lizards. In Anolis pulchellus the egg content which is very yolky is homogeneously distributed throughout the egg with no apparent presence of an egg white. Nevertheless, after resuspension in 0.02 M glycine (pH 7.2), a yolk pellet and a fraction with soluble proteins were separated by low-speed centrifugation. By chromatography in Sephadex G-100, the major egg yolk protein (S-1) was highly purified. This protein was characterized as a glyco-lipo-phosphoprotein with a mol wt of 110,000-120,000 as shown by SDS PAGE. By DEAE cellulose chromatography two acidic proteins (D-5; D-6) were purified (Mr = 62,000-66,000), which do not seem to be components of the yolk granules. Protein D-5 was shown to be a Fe2+ binding protein. By immunochemistry, the liver was found to be the site of synthesis of S-1 and D-5; both proteins are female specific. It is also demonstrated that S-1 shares several chemical and structural properties with the lipovitellins from other oviparous animals. PMID- 3111781 TI - The phylogenetic distribution of the liver protein F antigen. AB - F antigen is a liver protein of unknown function previously thought to be confined to class Mammalia. Using a recently developed radioimmunoassay, we show that F antigen can also be found in classes Aves, Reptilia, Amphibia and Osteichthyes. Ouchterlony gel diffusion (using murine antibodies) gave lines of identity or partial identity between mammalian F antigens, a line of identity between avian and reptilian F antigens (each showing partial identity to mammalian) and no precipitation with fish or amphibian F antigens. All immunopurified F antigens have molecular weights of 40,000-45,000. PMID- 3111780 TI - Tyrosination-detyrosination of the COOH-terminus of alpha-tubulin in oocytes and embryos of Bufo arenarum. AB - Soluble tubulin from Bufo arenarum oocytes and early embryos was shown to be composed mainly of the non-tyrosinable species. The low proportion of tyrosinable tubulin was almost exclusively constituted by the tyrosinated form. Compared with oocytes and embryos, toad brain contained a higher proportion of tyrosinable tubulin constituted mainly by the non-tyrosinated form. Tubulin carboxypeptidase was detected in toad brain but not in oocytes and embryos. PMID- 3111782 TI - Bacillus cereus bacteremia in an intravenous drug abuser. PMID- 3111783 TI - Ovulation detection following removal of levonorgestrel subdermal contraceptive implants. AB - The time to resumption of ovulation following the discontinuation of levonorgestrel subdermal implants (Norplant) was assessed in 10 women. A blood sample (2 ml) was taken at the time of Norplant removal and then twice weekly until the first evidence of ovulation (serum progesterone concentration greater than or equal to 5 ng/ml) was documented. Ovulation was resumed in 80% of the cases by 3 weeks and in all the cases by 7 weeks. Prompt return of ovulation following Norplant removal is an additional advantage of this mode of long-acting contraception. PMID- 3111784 TI - Plasma levels of levonorgestrel and free levonorgestrel index in women using NORPLANT implants or two covered rods (NORPLANT-2). AB - Plasma levels of levonorgestrel, sex hormone binding globulin (SHBG) and estradiol were studied during four years in 283 healthy women using either NORPLANT implants or two covered rods (NORPLANT-2). The women were randomized to use either type of implant. Both implant systems have previously been shown to have similar release rates of levonorgestrel. In both groups plasma levels of levonorgestrel decreased throughout the study, and there were no statistically significant differences between the two groups in mean plasma levels of levonorgestrel. During the study 8 women became pregnant. All pregnancies but one occurred after 35 months of implant use and only in women using the covered rods. No significant differences were seen between the women who became pregnant and the rest of the group using two covered rods with respect to plasma levels of levonorgestrel. SHBG capacity tended to be somewhat higher in women using the two covered rods. As levonorgestrel is to a great extent bound to SHBG, and in that form not biologically active, a "free levonorgestrel index" was calculated as a ratio between levonorgestrel and SHBG. This index was significantly lower in users of two covered rods than in users of NORPLANT implants at 1, 12 and 48 months of use. Women who became pregnant had significantly lower "free levonorgestrel index" than had the rest of the group. It is postulated that the difference in "free levonorgestrel index" between users of the two implant systems reflect differences in release rate, the covered rods having a lower release rate of levonorgestrel than NORPLANT throughout the observation period. It is concluded that "free levonorgestrel index" is a better parameter than levonorgestrel plasma levels to describe implant function, and to discriminate women who are at risk of pregnancy. PMID- 3111785 TI - Two years of intrauterine contraception with levonorgestrel and with copper: a randomized comparison of the TCu 380Ag and levonorgestrel 20 mcg/day devices. AB - IUDs releasing 20 mcg/day of levonorgestrel (LNg20) were in randomized trial together with the Copper T, model TCu 380Ag, in seven centers involving 2244 women. Two-year (25 months) gross cumulative pregnancy rates were 0.2 +/- 0.2 and 0.9 +/- 0.3 for the levonorgestrel and copper releasing devices, respectively (P greater than 0.05). There were no ectopic pregnancies in more than 1600 woman years of use of each device. Removal rates for bleeding and/or pain or for medical reasons other than menstrual problems did not differ significantly between devices. Oligomenorrhea or amenorrhea prompted 10.7 per hundred (gross rate, 8.4 net rate) women using the LNg 20 IUD to request removal in the two-year period, significantly above the 0.2 per hundred rate among women with the Copper IUD (P less than 0.001). At the end of two years an estimated 59.4 per 100 women were continuing use of the LNg 20 IUD, and 67.5 per 100 (P less than 0.001) with the TCu 380Ag. This difference is almost wholly ascribable to a marked reduction in bleeding episodes and days among women using the LNg 20 device with concomitant removal of device. Hemoglobin rose an average of 0.5 g/dl (P less than 0.001) for this group whereas women using the TCu 380Ag experienced a decline of 0.2 g/dl compared with baseline values (P less than 0.001). PMID- 3111786 TI - Glucose and lipid metabolism with triphasic oral contraceptives in women with history of gestational diabetes. AB - The glucose and lipid metabolism in a group of women with previous history of gestational diabetes were evaluated before and after 6 months treatment with a low-dose triphasic oral contraceptives pill (TP). This group was compared with a control group of women, also with history of gestational diabetes, using intrauterine devices (IUD). In the TP group, 26.7% of the women developed impaired glucose tolerance which reverted to normal in all but one after cessation of the TP. The IUD group showed no change in glucose tolerance. The integrated insulin response to a 75g OGTT in the TP group increased by 48.3% at 6 months compared with an increase of 23.4% for the same period in the IUD group. In the TP group there was a significant decrease in serum total cholesterol without changes in HDL-cholesterol and triglycerides level. We conclude that even low-dose triphasic oral contraceptive pills can cause glucose intolerance in women with previous gestational diabetes mellitus. PMID- 3111787 TI - 111In-oxine-labeled platelets in renal transplantation. Value in ciclosporin therapy. PMID- 3111789 TI - A comparison of methods to predict mortality of intensive care unit patients. AB - This paper presents results of the first study explicitly designed to compare three methods for predicting hospital mortality of ICU patients: the Acute Physiology Score (APS), the Simplified Acute Physiology Score (SAPS), and the Mortality Prediction Model (MPM). With respect to sensitivity, specificity, and total correct classification rates, these methods performed comparably on a cohort of 1,997 consecutive ICU admissions. In these patients from a single hospital, the APS overestimated and the SAPS underestimated the probability of hospital mortality. The MPM probabilities most closely matched the observed outcomes. Each method holds considerable promise for assessing the severity of illness of critically ill patients. The MPM should be particularly useful for comparing ICU performance, since it is independent of ICU treatment and can be calculated at the time a patient is admitted. PMID- 3111788 TI - A simple noninvasive method for assessing renal osteodystrophy. PMID- 3111791 TI - Methemoglobin, MEDLINE, and hyperlipemia. PMID- 3111790 TI - Comparison of noninvasive measurements of carbon dioxide tension during withdrawal from mechanical ventilation. AB - End tidal CO2 tension (PetCO2) and transcutaneous CO2 tension (PtcCO2) were compared with arterial CO2 (PaCO2) before and after withdrawal of mechanical ventilation in 20 patients predisposed to hypercarbia. With stable PaCO2 during mechanical ventilation, the correlation coefficient (r) between PaCO2 and PetCO2 was .9, and between PaCO2 and PtcCO2, .87. PtcCO2 considerably overestimated PaCO2 in three patients who were receiving dopamine. After withdrawal of mechanical ventilation, changes in PaCO2 were closely paralleled by changes in PetCO2 and PtcCO2 (r = .82 and .86, respectively). Nine of 20 patients had an increased PaCO2 of 10 torr or greater. In eight of these, PetCO2 and PtcCO2 rose by at least 5 torr, and in seven, the rise in PetCO2 and PtcCO2 was within 5 torr of the rise in PaCO2. During mechanical ventilation, PetCO2 and PtcCO2 estimated stable PaCO2 with sufficient accuracy for clinical use, except in patients with cutaneous vasoconstriction. After withdrawal of mechanical ventilation, changes in PetCO2 and PtcCO2 were predictive of important PaCO2 increases, warranting continued exploration and evaluation as to their use in monitoring patients predisposed to hypercarbia. PMID- 3111792 TI - Cyclo-oxygenase and lipoxygenase pathways in cynomolgus and rhesus monkey conjunctiva, anterior uvea and eyelids. AB - The capacity of cynomolgus and rhesus monkey conjunctiva, anterior uvea and eyelids to synthesize cyclo-oxygenase and lipoxygenase products from arachidonic acid was assessed. Both conjunctiva and eyelid tissues of cynomolgus and rhesus monkeys synthesized detectable amounts of cyclo-oxygenase and lipoxygenase products, indicating the presence of cyclo-oxygenase and 5- and 12-lipoxygenase activities in these tissues. In comparison, cynomolgus anterior uvea synthesized a considerably lesser amount of cyclo-oxygenase products. The cyclo-oxygenase activity was considerably greater than the lipoxygenase activity in cynomolgus and rhesus conjunctiva and eyelids. PMID- 3111793 TI - Adjuvant systemic therapy for early breast cancer. AB - The value of adjuvant endocrine therapy and adjuvant chemotherapy in improving the survival of patients with early breast cancer is still a subject of controversy after almost 40 years of clinical research in this area. The enormity of the adjuvant therapy literature is a challenge to the nonspecialist. The validity and importance of trial analyses often hinge on statistical methodology infrequently used by the clinician. For these reasons, this review is meant to serve as an easily accessible compendium of the large literature on the subject of adjuvant therapy and an intelligible guide around the pitfalls most often encountered in the analysis of this literature. The data utilized by the NIH Consensus Conference in September 1985 are summarized and the reasons for the conclusions reached by the consensus panel are both explained and extended. Trial data available through early 1986 justify the routine use of 6 months of adjuvant CMF in premenopausal women with histologically involved axillary lymph nodes. Postmenopausal women with histologically involved lymph nodes whose tumors also contain an estrogen receptor should routinely receive 2 years of adjuvant tamoxifen. In spite of promising preliminary reports, the treatment of all other patient groups and the use of other forms of adjuvant therapy must still be considered experimental. PMID- 3111794 TI - The long-term ventilator patient. A potentially disenfranchized medical population. PMID- 3111795 TI - Significance of the tuberculin test in the elderly. AB - Nine hundred thirty-three persons over 65 years of age, residing in long-term or extended-care facilities in Vancouver, Canada, had tuberculin tests. In addition to PPD-tuberculin, 5 TU and 250 TU, we used PPD-Battey, Candida albicans, mumps, and Trichophyton antigens. Twenty-five percent reacted to 5 TU of tuberculin with reactions of 10 mm or more. There was a progressive, substantial loss of reactivity with advancing age. Reactions to PPD-Battey greater than to PPD-T 5 TU were infrequent, suggesting that atypical mycobacterial infections were uncommon and that positive reactions to PPD-T, 250 TU, were predominantly caused by infections with Mycobacterium tuberculosis. Based on the results of both 5 TU and 250 TU, the prevalence of tuberculous infection exceeded 60 percent. Waning of tuberculin sensitivity appears to be an integral part of the aging process. Testing with nonmycobacterial antigens used in this study shed no further light on the problem of anergy in the elderly, as the number of reactors was smaller than that obtained with PPD-tuberculin. PMID- 3111796 TI - Patients with rheumatoid arthritis and gold-induced pneumonitis express two high risk major histocompatibility complex patterns. AB - Gold salt therapy-induced pneumonitis is a rare complication in patients with rheumatoid arthritis (RA). We studied HLA-A, B, C, D/DR, and complement factor B (Bf) and C4 alleles in 17 patients with RA and gold-induced pneumonitis and found that these patients had strikingly homogeneous major histocompatibility complex (MHC) markers. Eight of them (47 percent) had the alleles HLA-A3 B35 Dwl BfF C4A3,2 (BO), which were shown by family studies of some patients to be inherited as an extended MHC-haplotype with an apparent gene duplication in the C4A locus. The other high-risk phenotype, HLA-B40 with a C4 null allele, was found in eight patients (47 percent). All but three of the 17 patients had at least one of the two high-risk markers, the frequency of these combinations being clearly higher than in the two control groups: patients with RA but with no gold-induced side effects and healthy individuals. Our study shows that use of several MHC markers together results in a strong association between the markers and the disease. PMID- 3111797 TI - Some additional influences shaping the development of behavior. AB - The potent role played by neuroembryological forces in shaping brain development and function is well documented in Nowakowski's article. This discussion outlines several additional mechanisms whereby experience may directly influence brain structure and/or function. One such mechanism is the observation that altered sensory input in older primates may lead to anatomical and functional reorganization of sensory cortex. Another is the experimental evidence indicating that temporary disruption of social attachment bonds in young primates may produce longstanding alterations in behavior, immunological, and possibly other types of physiological functioning. Thus several routes exist whereby postnatal or even adult experiential influences may produce long-term alterations in behavior and physiological functioning, perhaps mediated by both anatomical and functional reorganization within the CNS. It is important to take into account all such potential mechanisms when considering the complex interplay between brain structure and function, experience, and behavior. PMID- 3111798 TI - [Endoscopic therapeutic procedures on the esophagus and stomach (without hemorrhage)]. PMID- 3111799 TI - [Endoscopic therapeutic interventions on the duodenum and Vater's papilla (with the small intestine)]. PMID- 3111800 TI - Conversion of post-elongation stage DNA to mature DNA occurs even if movement of the replication fork has stopped. AB - During DNA synthesis there is a distinct stage immediately after the joining of large DNA replication intermediates (post-elongation stage). The conversion of this DNA to mature DNA was analysed in cells treated with aphidicolin to stop the movement of the replication fork. In such cells mature DNA is formed. In contrast, UV-A, which induces a wide spectrum of DNA lesions, inhibits the conversion to mature DNA. The data indicate that the maturation of the post elongation stage can be uncoupled from the movement of the replication fork. PMID- 3111801 TI - Chromosome structure in four wild-type polytene tissues of Drosophila melanogaster. The 87A and 87C heat shock loci are induced unequally in the midgut in a manner dependent on growth temperature. AB - A systematic screen of wild-type Drosophila melanogaster larval organs has revealed three tissues besides the salivary gland with suitable polyteny for detailed cytogenetic analysis: the prothoracic gland, hindgut, and middle midgut. Chromosome banding patterns are very similar between tissues, but puffing patterns show considerable differences. In intact nuclei, oblique substructural elements can sometimes be detected in bands from some of the tissues. As a way of exploiting these newly characterized chromosomes, the heat shock puff response in midgut cells has been studied in detail. The puffing pattern is very similar to that in salivary glands, but an unexpected difference is found in the relative activity of the 87A7 and 87C1 loci, which contain the hsp70 genes. When larvae are raised at 16 degrees C, heat shocks ranging from 10 to 60 min induce only a weak midgut puff at 87A7 that is much smaller than that at 87C1, in contrast to other tissues where both are strongly induced. In pulse-labeled nuclei, an approximately five fold difference in transcriptional activity at the two loci is observed. However, when larvae are raised at 25 degrees C, the converse is found: the 87A7 puff is large, and little or no puffing is detectable at 87C1. Thus, in the midgut, heat shock induced puffing at these two loci is inversely modulated by a mechanism dependent on growth temperature. PMID- 3111803 TI - Arachidonic acid stimulation of mucus production by rat gastric cultured cells. AB - The effect of arachidonic acid (AA) on mucus production (synthesis and secretion) by rat gastric monolayer-cultured cells was investigated. For the study of mucus synthesis, the rate of incorporation of [3H]glucosamine into the cultured cells was measured. The rate of release of glycoprotein into the culture media from the cells, which were incubated in the medium containing [3H]glucosamine for 24 hr in advance, was determined for the study of mucus secretion. Prostaglandins in the medium were measured by radioimmunoassay. AA (10(-4) M) significantly increased mucus synthesis and secretion by the cultured cells (P less than 0.01). PG (E2 and I2) synthesis by the cultured cells was significantly enhanced by AA (10(-4) M) (P less than 0.05). An addition of indomethacin to the culture medium abolished this effect of AA. These results suggested that gastric mucus production was enhanced by AA in vitro and that this effect may be mediated by endogenous PG production. PMID- 3111802 TI - Induction of premature chromosome condensation in Drosophila melanogaster-rat heterokaryons. AB - After fusion mediated by polyethylene glycol (PEG) plus dimethyl sulfoxide (DMSO) between rat and Drosophila melanogaster cells cultured in vitro, the phenomenon of premature chromosome condensation (PCC) induced by mitotic rat chromosomes was detected in Drosophila nuclei. Exceptionally PCC was induced in rat nuclei but only in the presence of a very high ploidy level of Drosophila mitotic chromosomes. This provides further evidence of the lack of species specificity and of the effect of dosage of the PCC inducing factors, even among very distant species. PMID- 3111805 TI - Theophylline treatment in the neonate with apnea: effect on growth hormone, thyroid hormone and TRH induced TSH secretion. AB - Caffeine has been shown to markedly alter growth hormone (GH), thyroid stimulating hormone (TSH), and thyroid hormones in animal studies. Similar studies in the human are lacking. To determine the effect of theophylline treatment on endocrine function in neonates with apnea, 10 infants were studied prospectively pretreatment, immediately following therapeutic blood levels of theophylline, at 2, 4, and 6 weeks thereafter and finally 2 weeks after discontinuation of theophylline. T4, free T4, T3, GH, and basal and stimulated TSH were measured at each study period. Results show no significant difference consequent to theophylline therapy on basal thyroid or GH secretion and thyrotropin-releasing hormone (TRH) induced TSH response at any study interval. We conclude there is no evidence to suspect abnormality occurring in growth, thyroid function and GH secretion in neonates receiving theophylline for breathing disorders. PMID- 3111806 TI - Anaphylaxis. AB - The clinical syndrome of anaphylactic shock is a disorder produced by multiple mechanisms and pharmacological and environmental factors. The syndrome may be produced by both immunologic and nonimmunologic mechanisms and is due to the release of preformed biologically active mediators and the generation of biologically active mediators. The main mediator appears to be histamine. Although there are a number of defined predisposing factors, the majority of first reactions appear unpredictably. The mainstay of treatment is the use of epinephrine, volume replacement, and positive pressure ventilation. The follow-up and documentation of details of the reaction and exhaustive efforts to determine the precipitating factor are important aspects of the subsequent safety of the patient. History may be of more value than diagnostic testing. The use of H1 and H2 blockers, with steroids and sympathomimetics, may reduce the risk or magnitude of reactions in patients with a past history of a reaction. PMID- 3111804 TI - Effect of difluoromethyl ornithine (DFMO) on small intestine of adult and weanling rats. AB - Oral feeding of DL-difluoromethyl ornithine (DFMO) (2% in water ad libitum) for 14 days has no detectable effect on the small intestine of adult rats. Similar feeding of DFMO to weanling rat pups caused diarrhea in three to four days accompanied by a decrease in food consumption and body weight compared to age matched controls. Significant decreases in small intestinal mucosal weight, total protein, DNA, enterokinase, leucine amino peptidase, sucrase, and maltase contents were observed in the DFMO-treated group four days after treatment. Extending the treatment to seven days led to a more severe reduction in these parameters. Villous atrophy of the mucosa was demonstrable by light microscopy and morphometric measurements. The mucosa of the DFMO-treated rat pups showed a reduction in total thickness and villous height but no change in crypt depth. A significant reduction in villus-crypt ratio was also seen. Changes in small intestinal mucosal parameters were not due to a decrease in food intake since pair-fed, age-matched rat pups showed no biochemical changes compared to control pups. DFMO-treated weanling rats showed less than 5% of ornithine decarboxylase (ODC) activity when compared to age-matched control animals. The effects observed on the small intestinal mucosa are presumably due to inhibition of ornithine decarboxylase activities by DFMO which prevents the proliferation, regeneration, and maturation of epithelial cells. The relative insensitivity of the adult rat small intestine to DFMO treatment suggests a lesser dependence of its intestinal mucosa to ODC activities. PMID- 3111807 TI - [Recombinant gamma-interferon provides effective protection of cellular DNA against mutagens]. PMID- 3111808 TI - False positive reaction for urinary ketones with mesna. PMID- 3111809 TI - A key to the literature of total parenteral nutrition: update 1987. AB - This comprehensive bibliography is intended to enhance the education of the practitioner, student, and academician in the area of parenteral nutrition. This bibliography is not all-inclusive but serves as an update from the original published in 1983. Of particular note in this work is the addition of topics that reflect a growing interest in medical specialties with regard to patient nutritional status and support. PMID- 3111810 TI - Thrombocytopenia and vomiting due to difluoromethylornithine. AB - A 32-year-old Haitian male with acquired immunodeficiency syndrome presented with complications of Isospora belli enteritis. Therapy with the investigational drug difluoromethylornithine was initiated. Severe thrombocytopenia, nausea, and vomiting developed during intravenous drug therapy and recurred upon rechallenge with low-dose oral difluoromethylornithine. Therapy was discontinued because of these severe adverse effects. PMID- 3111811 TI - Growth of microorganisms in total nutrient admixtures. AB - It has been reported that intravenous fat emulsions, because of their isotonicity and neutral pH, support microbial growth, but traditional parenteral nutrition solutions, being hypertonic and more acidic, are not as supportive. To date, few studies have documented microbial growth in total nutrient admixtures (TNA) containing dextrose, amino acids, fat, electrolytes, vitamins, and trace elements. This study was undertaken to analyze the growth of Staphylococcus aureus, Candida albicans and four gram-negative enteric bacilli in three different nutrient admixtures, with and without the inclusion of 5% fat emulsion. The composition of the admixtures was either 5, 10, or 25% dextrose; either 0 or 5% fat; and 3% amino acids, electrolytes, vitamins, and trace elements. All admixtures were innoculated with 100 colony-forming units per milliliter, incubated at room (25 degrees C) or refrigerated (4 degrees C) temperature, with samples withdrawn at 0, 3, 6, 12, 24, and 48 hours and plated in triplicate. Only C. albicans demonstrated any significant growth regardless of fat content. The pH of the admixtures was similar (acidic), and all solutions were hypertonic and found to inhibit bacterial growth. Conclusions suggest that TNA, when formulated with normal concentrations of additives, is no more likely to support growth of contaminant organisms than the traditional solutions. This contradicts the notion that the addition of fat to total parenteral nutrition will enhance the ability of these admixtures to support microbial growth. PMID- 3111812 TI - Comparative evaluation of the three commercially available transdermal nitroglycerin delivery systems. AB - We comparatively evaluated the patient preference for each of the three commercially available transdermal nitroglycerin delivery systems using a randomized crossover study design. Preference was determined by ease of application, adhesion, occurrence of local irritation at the site of application, and systemic toxicities. In addition, we recorded the number of nitroglycerin tablets taken and angina attacks reported per treatment course. Each treatment course was one month long, with each patient participating for a total of three months. This allowed all patients to be exposed to each of the three products for one treatment course, thereby serving as their own controls. Thirty-eight patients completed the three-phase crossover and expressed a preference. Results showed that Transderm-Nitro was significantly preferred over both Nitro-Dur and Nitrodisc (p less than 0.005). Most of the preferences were based on cosmetic appearances or adhesive qualities. Additionally, results showed that there was no difference in efficacy among the three products when number of angina attacks reported and number of nitroglycerin tablets taken were compared. PMID- 3111813 TI - Drug therapy team review in a long-term care facility. PMID- 3111814 TI - Specific change of histamine metabolism in acute magnesium-deficient young rats. AB - The effects of dietary magnesium (Mg) deficiency on histamine metabolism were studied. Young Wistar rats were fed a Mg-deficient diet (0.001% Mg diet) ad libitum for 8 days with control groups (0.07% Mg diet), food-restricted groups (0.21% Mg diet, but restricted to 5 g/rat/day), and refeeding groups (0.001% Mg diet for 6 days ad libitum, after that fed with a 0.21% Mg diet ad libitum for 2 days). Compared to the other groups, the plasma Mg level was markedly lower in the Mg-deficient group. A return from the lower Mg level to the controls took place after feeding them a 0.21% Mg diet for 2 days. Urinary histamine level increased rapidly after 4 days and reached a maximum on the eighth day of Mg deficiency. The high urinary histamine level in Mg-deficient rats decreased rapidly after feeding them a 0.21% Mg diet for 2 days. Histamine contents in some tissues increased on the eighth day of Mg deficiency. Other groups showed no significant change. The increased histamine content in Mg-deficient rats showed a tendency to return to control levels after feeding them a 0.21% Mg diet for 2 days. Histidine decarboxylase (HDC) activity in some tissues of Mg-deficient rats increased markedly. The increased HDC activity dropped nearly to control levels after feeding them a 0.21% Mg diet for 2 days. Diamine oxidase (DAO) activity in the duodenum was high in control rats. Duodenal DAO activity decreased gradually and reached half the value of controls on the eighth day of Mg deficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3111815 TI - [Treatment of diabetic ketoacidosis]. PMID- 3111816 TI - [Function-preserving treatment of anal cancer using simultaneous radio- and chemotherapy]. AB - Since 1985, twelve patients with anal carcinoma underwent simultaneous radiation and chemotherapy as primary treatment. The primary tumor region and the regional lymph drainage area received a total dose of 30 Gy over three weeks or 50 Gy over five weeks. During the first week of radiotherapy, 5-fluorouracil (1000 mg/m2 daily for four days by continuous infusion), and mitomycin (10 mg/m2 on day 1) were administered; four weeks later, a second cycle at the same dosage followed. This treatment schedule was well tolerated by all patients and all tumors responded. In only one patient was the tumor still palpable at the end of the treatment period. In eight patients a biopsy was obtained from the primary tumor region four weeks after treatment had ended: in six of them no further operative treatment was necessary, because no evidence of tumor was found in the biopsy. It is concluded from these results that simultaneous radiation and chemotherapy is the best primary treatment of anal carcinoma. PMID- 3111817 TI - [Balloon ileus as an unusual complication of enteral tube feeding]. AB - Total enteric feeding through a filiform indwelling catheter is being used more and more. Various indwelling catheters have been developed for this purpose, one of them a catheter (Salvisond) which has a "pulling" balloon, for advancing the catheter tip through the stomach into the small intestine, while a retaining balloon is inflated, once the tip has reached its final location, to prevent its dislocation. In a patient with Crohn's disease the retaining balloon, for unforeseeable and unexplained reasons, expanded further in situ and could not be deflated, causing a small-intestinal ileus and requiring operative removal of the catheter. PMID- 3111818 TI - [Effect of tolazoline on xylazine-induced changes in acid-base balance and arterial oxygen partial pressure in cattle]. PMID- 3111819 TI - Some cardiovascular and respiratory effects of alfentanil in animals. PMID- 3111820 TI - [Myeloma and the kidney]. PMID- 3111821 TI - A double blind comparison of a new paediatric amino acid solution in neonatal total parenteral nutrition. AB - All infants requiring parenteral nutrition over a continuous 13-month period were allocated to receive either Vamin or a new paediatric amino acid solution, Paedmin, as their protein source in a double blind prospective study. Those of 32 weeks gestation and less gained weight more rapidly when fed Paedmin than Vamin (P less than 0.004), but there were significant changes in liver function after 14 days nutrition. Babies of 33 weeks gestation and greater gained weight more rapidly when fed Vamin than Paedmin (P less than 0.003) but without liver function changes. There were no differences in the rate of head growth. Amino acid analysis of serum and urine showed a greater urinary loss of amino acids for a given serum concentration in babies of 32 weeks and less for both nutrition groups. The apparent benefit of Paedmin in the immature group of infants must be further evaluated and weighed against changes in liver function. PMID- 3111822 TI - [Sovol as an inducer of procarcinogen activating microsomal enzymes]. AB - The commercial mixture of polychlorinated biphenyls (Sovol) studied by biochemical and immunochemical methods was found to be an inducer of a wide range of cytochrome P-450 isoenzymes. The induced enzymes activated in the Ames test a series of procarcinogens differing both in structure and in target organs: benz(a)pyrene, 3-methylcholanthrene, nitrosomorpholine, dimethylnitrosamine, aflatoxin B1, orthoaminoazotoluene, 2-acetylaminofluorene, cyclophosphamide and benzidine. According to the parameters the studied Sovol is similar to Aroclor 1254 and may be recommended to be used as an inducer of microsomal enzymes in routine tests for carcinogen screening. PMID- 3111823 TI - [Polyamine levels and diamine oxidase activity in the rat liver and kidneys during hepatocarcinogenesis induced by N-nitrosodiethylamine]. AB - Changes in the polyamine metabolism in the liver and kidneys have been studied in rats with N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis and under diethylamine administration. It is found that the intracellular content of polyamines rises and the diaminooxidase activity falls in the liver (but not in the kidneys) of rats who were given NDEA in drinking water. These changes are most pronounced during the first month of carcinogenesis and in the induced tumours. It is a typical (though not specific) biochemical peculiarity of hepatocarcinogenesis. PMID- 3111824 TI - [Ratio of polyamine synthesis and oxidation enzymes during cell proliferation and differentiation]. AB - Difluoromethylornithine (DFMO) was studied for its effect on the aminoxidase activity in the culture media during proliferation and differentiation of mouse fibroblasts. Single introduction of difluoromethylornithine into the culture medium increases the polyamine oxidase activity during 12 to 24 hours after the action. In the subsequent periods DFMO in 0.1 to 1 mM concentrations inhibits the proliferation and differentiation, but 0.01 mM concentration leads to their acceleration, which correlates with higher or lower aminoxidase activities respectively in the culture media. PMID- 3111825 TI - [Characteristics of the inhibition of thymus endocrine function and synthesis of substances with thymosin-like activity caused by thymostimulin and splenin during DMBA-induced mammary gland carcinogenesis in rats]. AB - The contents of thymic hormones and endogenous substances with thymosin-like activity (TLA) was studied under conditions of administering thymostimulin and splenin during DMBA-induced carcinogenesis in rat mammary glands. It has been established that during latent carcinogenesis there is an inhibition of thymic endocrine function which persists in tumour-bearing animals. Injections of thymostimulin and splenin induce synthesis of substances with TLA, accompanied by an inhibition of blastoma development. PMID- 3111826 TI - [Relations between the cortical DC potentials and the K+ concentration of the blood and cerebral cortex extracellular space in reversible asphyxia]. AB - The relationship between changes of the cortical DC potential and the K+ concentration gradient across the blood-brain barrier (BBB) was studied in the rat brain during short ventilatory arrest. For this purpose K+ concentrations were measured simultaneously in the extracellular space of the cerebral cortex and in the streaming blood of the carotid artery and the superior sagittal sinus. For measurements ion-selective micro- and macro-electrodes based on the K+ ionophore valinomycin were used. During reversible asphyxia free K+ concentrations in the circulating blood and in the extracellular fluid of the brain tissue increased and re-decreased with different time courses. The resulting difference between the electromotive forces of the ion-selective signals resembled the course of the cortical DC potential during the initial phase of the ventilatory arrest during the post-asphyxiation period. The results suggest that during these events the cortical tissue including the BBB behaves like a K+-selective membrane which is probably located at the blood-brain interface. It is concluded that the capillary-glial complex may principally contribute to the generation of DC shifts associated with the asphyxiation process. PMID- 3111827 TI - [Are cognitive processes related to the EEG alpha phase? An experimental study using P300]. AB - Different models have been developed in the past to explain the functional significance of the EEG alpha rhythm. This rhythm has been viewed as an expression of a scanning mechanism, of an inner clock or of an excitability cycle. Based on these conceptions, several older works dealing with EEG alpha phase and reaction time suggest that the EEG may also serve as a gating mechanism for cognitive information processing. The purpose of this investigation was therefore to determine the existence of a possible correlation between P300 and the background EEG. P300 was used as a neuroelectrical correlate of a cognitive decision-making process. However no significant relationship between P300 latency period and EEG alpha phase was found. The variability of P300 can therefore not be explained in this way. PMID- 3111829 TI - [Direct measurement of the conduction velocity of single motor axons in man]. AB - The conduction velocity (CV) of single motor axons was measured in the ulnar and median nerve. Stimuli of submaximal intensities were delivered at the wrist and at the elbow using surface electrodes. The responses of single motor units were recorded by tungsten or steel microelectrodes. Changes of the stimulus intensity and of the position of the stimulation electrodes and subtraction of the responses frequently allowed the potential of the same motor unit to be identified following stimulation at both sites and to calculate its axonal CV. In all individuals, axonal CV's from the low to the high velocity range (40 to 63 m/s) could be measured. The method may provide a new approach to the investigation of various disorders of the peripheral nerve. PMID- 3111828 TI - [Effect of lormetazepam, triazolam and flunitrazepam on rapid eye movements, K complexes and sleep spindles in normal probands]. AB - "Equipotential" doses of lormetazepam, triazolam and flunitrazepam were tested regarding their influence on K-complexes, sleep spindles and rapid eye movements. The receptor affinity was used to determine the equipotency. In this respect triazolam, lormetazepam and flunitrazepam show a relationship of 1:2:4. Lormetazepam, however, showed only slight changes of the three neurophysiological parameters even when given as double dosage. Triazolam and flunitrazepam reduce K complexes considerably, increase sleep spindles enormously and reduce REM activity markedly; both substances suppress the first REM period, flunitrazepam even the second one. All three of the benzodiazepines have the same effect on the dissociation of K-complexes and sleep spindles; epochs with K-complexes or sleep spindles are favored compared to epochs with K-complexes and sleep spindles. The general reduction of K-complexes and the increase in sleep spindles can be interpreted as a sleep protective function. When deciding on the dosage, however, REM-suppression should be used as a guide since it has the strongest effect on the cyclic structure of sleep which nowadays is considered to be the safest evidence of well balanced sleep behavior. PMID- 3111830 TI - [Relation of the duration of muscle action potentials to intramuscular temperature]. AB - On 40 motor unit potentials recorded from the abductor digiti quinti muscle of 4 normal subjects the alteration of shape and duration under the influence of decreasing temperature (36 to 22 degrees C) has been examined. The mean increase of duration was about 6%/degrees C for the temperature range between 36 and 30 degrees C and about 9%/degrees C for the range between 30 and 22 degrees C. A significant alteration of shape, e.g. an increased incidence of polyphasic potentials as observed by Buchthal, could not be demonstrated. This prolongation of motor unit potential's duration probably results mainly from an increased temporal dispersion of impulse propagation in the terminal branches of motor nerve fibres and from a delayed impulse conduction over the muscle fibre membrane. PMID- 3111832 TI - [Effect of the time of day on the EEG in cerebral arteriosclerosis]. AB - The study was conducted with three men and seven women, 72-84 years old, characterized by psychopathological and clinical signs of cerebral arteriosclerosis (A). All patients suffered from disorder of sleep-waking rhythm. With one exception every experiment ran for five days during which closed-eye EEGs were registered at 8 a.m., 12 noon, 4 p.m., and 8 p.m. of the alert but relaxed patients and recorded on tape for computer processing. Simultaneously with every EEG registration the body temperature was measured. The findings were compared statistically with corresponding data of a former study conducted with ten healthy aged volunteers (G). RESULTS: The dominant peak-frequency of the patients turned out significantly slower than that of the volunteers.--While in healthy persons the peak frequency increased corresponding with the body temperature from the morning to the late afternoon or the early evening respectively, the patients lacked such a correlation, although their temperatures rose gradually in the normal way. In most of the patients the peak-frequency had a remarkable small variety from day to day as well as from scalp-position, and its circadian shift was poor. Psychopathologically these subjects manifested primarily memory loss, general intellectual decline, and in four cases disorientation. On the other hand the EEGs of three women showed substantial greater variety of the peak-frequency from day to day and from scalp-position to scalp-position. Besides the alterations during the day were rather excessive, but lacking any appreciable correspondence with the undisturbed circadian variations of the body temperature. In these three cases psychopathologically personality changes preponderated. PMID- 3111831 TI - [Electrically induced cutaneo-muscular reflex from the m. extensor digitorum brevis]. AB - We recorded the cutaneo-muscular reflexes in 90 normal subjects from the extensor digitorum brevis muscle following electrical stimulation at the second toe. In 88 subjects an early and a late EMG response were obtained. The mean latency of the second reflex response was 91.9 +/- 12.1 ms and the mean duration was 27.3 +/- 11.6 ms. However, there was considerable variability of the interindividual amplitudes. Comparison of the age related changes in the latencies of the first and second reflexes yielded results consistent with the transcortical or spino bulbo-spinal hypothesis. PMID- 3111833 TI - [EEG changes in cerebrovascular ischemia as affected by cardiac arrhythmias]. AB - 124 patients with cerebrovascular ischemic disease were studied, 67 of them with irreversible neurological deficits, and the EEG-findings of patients with (50) or without cardiac arrhythmia (74) were compared. Moreover, the EEG-diagnoses of these patients were compared with 40 controls without cerebrovascular ischemic disease. Patients with irreversible neurological deficit had significantly more often cardiac dysrhythmia (51%) than patients with reversible neurological symptoms (28%). In patients with reversible neurological symptoms and in the control group no difference between patients with or without disturbance of the heart rhythm could be found. But in patients with irreversible neurological deficit in presence of cardiac dysrhythmia significantly more pathological EEG findings could be found with significantly more pronounced EEG changes especially in presence of atrial fibrillation. PMID- 3111834 TI - [Cortical somatosensory evoked potentials following median and tibial nerve stimulation in multiple sclerosis; relation to sensory disorders and duration of the disease]. AB - In 40 patients with multiple sclerosis, 11 of whom presented with their first disease manifestation, cortical somatosensory evoked potentials following median and tibial nerve stimulation were examined. 45 percent of the patients with first manifestation had at least one pathological SEP, while 79 percent of the patients with longer course of the illness showed pathological SEPs. The group of patients with first manifestation differs significantly in this aspect from the group of those patients with longer duration of the illness. The occurrence of pathological SEPs was associated significantly more often with impairment of joint position and vibration sense, than with nonspecific sensory disturbances. Not only in some patients with first manifestation, but also in some patients with long, but mild courses, there were nonspecific sensory disturbances in association with normal SEPs. One should not underestimate the complaints in such cases. PMID- 3111835 TI - [Value of the EEG in the prognosis of post-anoxic coma following cardiocirculatory arrest]. AB - The EEGs of 26 patients who remained at least 6 hours in coma after cardiovascular arrest were analyzed. The first EEG was recorded within few days after reanimation, classified in a 5-grade scale of increasingly severe impairment and compared with the final clinical outcome. On the basis of the present study and of a review of 408 EEG findings reported in similar investigations in the literature we conclude that the EEG can be useful in predicting the outcome of patients in postanoxic coma states: the EEG should be recorded at earliest 8-12 hours but within 2 days after reanimation, a barbiturate intoxication and hypothermia should be excluded. The classification of the recordings in a 5-grade scale has proven to be helpful and accurate in predicting the outcome: Grade I EEG findings imply a very good prognosis, a complete remission can be expected in most cases. Grade II and III findings have no definite prognosis: the EEG should be repeated one or two days later, a favorable outcome is to be expected only with rapid improvement of the tracing. Grade IV and Grade V findings have a very serious prognosis: complete recovery has been described episodically, most in the pediatric population and with findings of alpha-coma. PMID- 3111836 TI - Effect of follicular fluid on the maturation of porcine granulosa cells: stability of luteinization stimulator. AB - The effect of follicular fluid on FSH stimulated progesterone secretion and LH/hCG receptor induction was studied in granulosa cells harvested from small porcine follicles. The stability of the stimulatory factor was also assessed. Follicular fluid from large porcine follicles (LFF) added to the culture of granulosa cells in the dilution from 1:32 to 1:3 stimulated progesterone secretion, while at higher concentrations (dilution 1:2 and 1:1) it had an inhibitory effect. In contrast, the influence of follicular fluid on the induction of LH/hCG receptor was stimulatory only in the concentration of LFF diluted from 1:3 to 1:1. When the granulosa cells were cultured with follicular fluid in the absence of pig serum the effect on both progesterone secretion and hCG binding was stimulatory in all the concentrations of follicular fluid tested. Different treatment of follicular fluid (charcoal extraction temperature treatment, lyophilization, dialysis, ethanol precipitation, delipidation and ether extraction) showed that the stimulator of granulosa cell luteinization was not a stable compound. PMID- 3111837 TI - Effects of low and high dose oral cimetidine on hormone serum levels in patients with peptic ulcers. AB - Luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (hPRL) and testosterone (T) were assayed in a total of 131 patients with peptic ulcer. Initial oral treatment was performed with 1000 mg cimetidine per day for 6 to 12 weeks. After healing was confirmed endoscopically, the patients were switched to a maintenance dose of 400 mg per day cimetidine for 3 years. Serum hormone levels before and during the two regimens were estimated in 48 male, 22 postmenopausal and 5 premenopausal subjects. Comparison between the two cimetidine doses was possible in 76 male, 44 postmenopausal and 6 premenopausal patients. In all patients hormone parameters assayed before therapy were within the normal ranges. FSH was noted to increase significantly in all but the premenopausal group but remained within the normal range. In contrast, hPRL declined significantly in all groups of subjects except for premenopausal females during cimetidine treatment. LH and T did not change during treatment and no differences of hormone serum levels were noted between the two regimens. Present data combine to suggest that an initial treatment with 1000 mg of cimetidine per day did not provoke hyperprolactinemia, and a switch from an initial high dose to a maintenance dose of 400 mg per day did not cause further changes in hormone serum levels. Changes of LH, FSH, hPRL and T recorded in the present study are too small to be considered responsible for possible endocrine disorders observed during cimetidine therapy. PMID- 3111838 TI - Growth hormone releasing and inhibin-like activity in rat uterus: an in vitro study. AB - Cytosol from uteri of intact rats stimulated growth hormone (GH) release from anterior pituitary cells in vitro. Cytosol from uteri from ovariectomized (OVX) animals had the same effect, but approximately 30-times less. Estradiol treatment in vivo increased such activity in the uteri of OVX rats. To characterize and partially purify this GH releasing activity, crude extracts from uteri of intact and OVX rats, from liver, and plasma were fractionated on Sephadex G-100 superfine columns and the effects of different fractions on the synthesis and release of GH studied and compared to the effects on the synthesis of thyrotropin (TSH), follitropin (FSH), and lutotropin (LH). Fractions containing molecules with high molecular weight (MW greater than or equal to 40,000, HMWF) in these tissues and plasma stimulated GH release. Furthermore, fractions containing molecules with lower MW (10,000-20,000, LMWF) from intact uteri and plasma, but not from uteri of OVX rats and liver had similar GH-releasing activity. LMWF from uteri of both intact and OVX rats but not from plasma and liver inhibited FSH synthesis without having any effects on LH synthesis. Tissue and plasma fractions did not show any effects on TSH and LH synthesis. It was concluded that the rat uterus contained two GH-releasing activities: one which was associated with HMWF and the other one with LMWF. The GH-releasing activity in LMWF was probably induced by estradiol and secreted into the plasma. Furthermore, inhibin-like activity was present in LMWF from uteries. PMID- 3111839 TI - Ketoconazole as a possible universal inhibitor of cytochrome P-450 dependent enzymes: its mode of inhibition. AB - Modes of inhibition and binding of ketoconazole, an orally antimycotic agent, to NADPH-cytochrome P-450 dependent enzymes were investigated using subcellular fractions of human and rat testes, human adrenocortical adenoma tissue and rat adrenals and livers. Ketoconazole competitively inhibited the activities of steroid 17 alpha-hydroxylase and C17-20 lyase in rat and human testes, 16 alpha hydroxylase in human testes and 21-hydroxylase in rat adrenal glands. Ki values were in the order of 10(-8)M for human testicular enzymes, while the order was 10(-7)-10(-6) M for rat adrenal and testicular enzymes. Kinetic studies indicated that ketoconazole bound to cytochrome P-450 and not to other components of monooxygenase systems. Spectrophotometric studies also revealed direct binding of ketoconazole to cytochrome P-450 component by inducing type II difference spectra in all tissue preparations examined, indicating that ketoconazole is possibly a universal inhibitor of NADPH-cytochrome P-450 dependent monooxygenases which are involved in metabolism of many substances including steroids, toxins, carcinogens and others. PMID- 3111840 TI - Plasma growth hormone (GH) response to GH-releasing factor (SM-8144) in children of short stature and patients with GH deficiency. AB - Synthetic human GRF (hGRF (1-44) NH2; SM-8144) was administered as an iv bolus to 141 normal children of short stature (NSC), 73 patients with severe idiopathic GH deficiency (IGD; group A), 30 patients with mild idiopathic GH deficiency (IGD; group B), 29 patients with secondary GH deficiency, 3 patients with primary hypothyroidism, 21 patients with Turner's syndrome and 25 patients with various other disease. Their height was below normal for their age and sex, and they were all below 25 years old without obesity. The maximal GH responses (M+SEM) were 39.5 +/- 2.2, 7.2 +/- 0.9, 27.2 +/- 3.7, 5.2 +/- 0.8, 9.7 +/- 4.4, 25.1 +/- 2.8 and 32.3 +/- 4.8 ng/ml, respectively (significance from the NSC, ; p less than 0.05, ; p less than 0.001). The GH responses to hGRF were greater than those elicited by standard pharmacological tests. There was a negative correlation between bone age and peak plasma GH response to hGRF in patients with idiopathic GH deficiency (IGD) but not in normal children (NSC). In twenty-two percent of the patients with IGD in group A the response was above 10 ng/ml and in 57% of the patients with IGD in group B the response was above 20 ng/ml, suggesting that a large percentage of patients with idiopathic GH deficiency lack hypothalamic GRF. The side effect of flushing was observed in 15.2% of all subjects. These results indicate the potential usefulness of hGRF (1-44) NH2 (SM-8144) in inducing GH release from the pituitary. PMID- 3111841 TI - Short term treatments with prolactin, HMG or testosterone fail to affect testicular inhibin content in rats. AB - To investigate the effect of prolactin (PRL) on testicular function, especially on spermatogenesis, testicular inhibin content in male rats treated with PRL was compared with those treated with HMG and testosterone. Mature Wistar male rats were given 10 or 50 IU of ovine PRL, 10 IU of HMG and 5 mg of testosterone, i. m. for 5 consecutive days and testes were removed for assessing inhibin content. Inhibin content was measured by a FSH suppressing activity in cultured rat anterior pituitary cells using aquous extract of testes. Five days' treatment with PRL, HMG, or testosterone did not influence testicular inhibin content in male rats. The possibility that these treatments had transiently affected testicular inhibin content, or that inhibin content did not reflect inhibin production was not ruled out. PMID- 3111842 TI - Inhibitory effect of progesterone in the postcastration gonadotrophin rise in women. AB - This study was designed to investigate the effects of progesterone on the gonadotrophin rise after bilateral salpingo-oophorectomy (BSO). Twenty-eight regularly menstruating women underwent hysterectomy and BSO during the follicular phase of the menstrual cycle. They were divided into 5 groups depending on the treatment after BSO. Plasma LH and FSH were studied serially for 14 days after BSO and the patterns of LH and FSH rises were contrasted to those observed in the control group which received neither progesterone nor estrogen. LH and FSH levels in the group which were given low dose progesterone only, rose consistently after BSO and these patterns were similar to those seen in the control group. However, the addition of estrogen reduced gonadotrophin rises significantly more than estrogen did alone. Further, the luteal phase level of progesterone solely has a suppressive effect on the gonadotrophin rises after BSO. Our observations suggest that synergism of progesterone with estrogen may exist in suppressing gonadotrophin secretion in the normal luteal phase and should help in understanding why gonadotrophin levels in the luteal phase are lower than those in the follicular phase of the menstrual cycle. PMID- 3111843 TI - Determination and characterization of succinyl tri-alanine p-nitroanilide hydrolyzing metalloendopeptidase in serum. AB - Serum succinyl (Ala)3-p-nitroanilide hydrolyzing elastase-like activity which elevates in patients with obstructive jaundice, is due to the joint action of two enzymes: first, succinyl (Ala)3-p-nitroanilide is cleaved to succinyl (Ala)2 and Ala-p-nitroanilide by metalloendopeptidase, and then Ala-p-nitroanilide is cleaved to Ala and p-nitroaniline by aminopeptidase. We adopt a new assay method for serum endopeptidase activity using HPLC. PMID- 3111844 TI - Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts. AB - We have studied the mechanism of a transforming growth factor-beta (TGF-beta) stimulated production of type-1 plasminogen activator inhibitor (PAI-1) in WI-38 human lung fibroblasts. TGF-beta causes an early increase in the PAI-1 mRNA level which reaches a maximal 50-fold enhancement after 8 h. Blocking of protein synthesis with cycloheximide causes an equally strong increase in the level of PAI-1 mRNA. Quantitative studies of the effect of TGF-beta on PAI-1 protein levels in cell extracts and culture media by using monoclonal antibodies are consistent with the effect on PAI-1 mRNA. The results suggest a primary effect of TGF-beta on PAI-1 gene transcription, and also suggest the possibility that the transcription of this gene in non-induced cells may be suppressed by a short lived negatively regulating protein. Urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators are decreased in the culture media of TGF-beta-treated cells concomitantly with the increase in PAI-1 accumulation. These findings show that a primary and important biological effect of TGF-beta may be an overall decreased extracellular proteolytic activity, and give an insight into the molecular mechanisms underlying TGF-beta action at the genetic level. PMID- 3111845 TI - The conserved decanucleotide from the immunoglobulin heavy chain promoter induces a very high transcriptional activity in B-cells when introduced into an heterologous promoter. AB - A conserved decanucleotide (ATGCAAATNA) is present 45-60 nucleotides upstream from the transcription startpoint in all immunoglobulin heavy chain promoters (VH promoters). We have introduced this decanucleotide (cd sequence) at a similar position into the upstream flanking sequence of the mouse Renin-1 gene. This gene is only transcribed in highly specialized tissues, and the fragment used here ( 449 to +30 with respect to the main transcription startpoint) has little promoter activity in fibroblastic or myeloma cell lines, even if coupled to a functional enhancer. In contrast, after insertion of the decanucleotide, this fragment, while still inactive in non-lymphoid cells, becomes a potent promoter in B-cells when associated with SV40 or immunoglobulin heavy chain enhancer. In all respects, the engineered fragment behaves like an authentic VH promoter isolated in this laboratory, except that it is even more active in B-cells. Deletion experiments show that all renin sequences are dispensable for the activity of the chimaeric promoter, except probably for the renin TATA box which defines the precise transcription startpoint. We conclude that the decanucleotide is sufficient to activate a promoter in B-cells but not in non-B-cells, and therefore that no other element is needed to account for the B-cell specificity of the VH promoter. In addition, our results suggest that the lack of activity of the renin promoter in non cognate cells is not due to the binding of a repressor. PMID- 3111847 TI - The epidemiology of Schistosoma mansoni around Lake Zway and its islands, Ethiopia. PMID- 3111846 TI - (dC-dA)n.(dG-dT)n sequences have evolutionarily conserved chromosomal locations in Drosophila with implications for roles in chromosome structure and function. AB - In situ hybridization of (dC-dA)n.(dG-dT)n to the polytene chromosomes of Drosophila melanogaster reveals a clearly non-random distribution of chromosomal sites for this sequence. Sites are distributed over most euchromatic regions but the density of sites along the X chromosome is significantly higher than the density over the autosomes. All autosomes show approximately equal levels of hybridization except chromosome 4 which has no detectable stretches of (dC dA)n.(dG-dT)n. Another striking feature is the lack of hybridization of the beta heterochromatin of the chromocenter. The specific sites are conserved between different strains of D. melanogaster. The same overall chromosomal pattern of hybridization is seen for the other Drosophila species studied, including D. simulans, a sibling species with a much lower content of middle repetitive DNA, and D. virilis, a distantly related species. The evolutionary conservation of the distribution of (dC-dA)n.(dG-dT)n suggests that these sequences are of functional importance. The distribution patterns seen for D. pseudoobscura and D. miranda raise interesting speculations about function. In these species a chromosome equivalent to an autosomal arm of D. melanogaster has been translocated onto the X chromosome and acquired dosage compensation. In each species the new arm of the X also has a higher density of (dC-dA)n.(dG-dT)n similar to that seen on other X chromosomes. In addition to correlations with dosage compensation, the depletion of (dC-dA)n.(dG-dT)n in beta-heterochromatin and chromosome 4 may also be related to the fact that these regions do not normally undergo meiotic recombination. PMID- 3111848 TI - The structure of NADH:ubiquinone oxidoreductase from beef-heart mitochondria. Crystals containing an octameric arrangement of iron-sulphur protein fragments. AB - We have investigated the structure of two-dimensional crystals from preparations of NADH:ubiquinone oxidoreductase from beef-heart mitochondria. The crystal structure of these crystals was previously determined to be equivalent with two native enzyme molecules per unit cell, i.e. a p2 symmetry [Boekema, E. J., Van Heel, M. G. & Van Bruggen, E. F. J. (1984) Biochim. Biophys. Acta 787, 19-26]. However, the optical diffraction patterns of the crystals displayed a clear fourfold symmetry. A Fourier analysis carried out on the calculated diffraction pattern proved unambiguously that the crystal symmetry was p42(1)2. Following crystallographic rules the unit cell therefore contained eight identical molecules. As a consequence, only a subcomplex of the enzyme rather than the intact enzyme formed the crystal. Electron microscopy of isolated, single molecules of the iron-sulphur protein, a dissociation product of complex I, revealed the presence of square complexes with sides of approximately 15 nm. Since these complexes were indistinguishable from the building blocks (unit cells) of the two-dimensional crystals, the crystals could be composed of Fe-S protein fragments only. The nature of the fragments in the unit cell was probed by immuno-labelling with monovalent antibodies (Fab's), raised against the 75-kDa subunit from the Fe-S protein, followed by image analysis. We found at least four binding sites for the anti-(75-kDa subunit) Fab per unit cell, indicating the presence of at least four copies of the antigen. In order to account for these observations we postulate the hypothesis that the two-dimensional crystals obtained from complex I are composed of iron-sulphur protein molecules in an octameric arrangement. PMID- 3111850 TI - Spectral and potentiometric analysis of cytochromes from Bacillus subtilis. AB - Bacillus subtilis cytoplasmic membranes contain several cytochromes which are linked to the respiratory chain. At least six different cytochromes have been separated and identified by ammonium sulphate fractionation and ion-exchange chromatography. They include two terminal oxidases with CO-binding properties and cyanide sensitivity. One of these is an aa3-type cytochrome c oxidase which has characteristic absorption maxima in the reduced-oxidized difference spectrum at 601 nm in the alpha-band and at 443 nm in the Soret band regions. In the alpha band two separate electron transitions with Em = +205 mV and Em = +335 mV can be discriminated by redox potentiometric titration. The other CO-binding cytochrome c oxidase contains two cytochrome b components with alpha-band maxima at 556 nm and 559 nm. Cytochrome b556 can be reduced by ascorbate and has an Em + +215 mV, whereas cytochrome b559 has an Em = +140 mV. Furthermore a complex consisting of a cytochrome b564 (Em = +140 mV) associated with a cytochrome c554 (Em = +250 mV) was found. This cytochrome c554, which can be reduced by ascorbate, appears to have an asymmetrical alpha-peak and stains for heme-catalyzed peroxidase activity on SDS-containing polyacrylamide gels. A protein with a molecular mass of about 30 kDa is responsible for this activity. A cytochrome b559 (Em = +65 mV) appears to be an essential part of succinate dehydrogenase. Finally a cytochrome c550 component with an apparent mid-point potential of Em = +195 mV has been detected. PMID- 3111852 TI - pH-dependent interconvertible allosteric forms of murine melanoma tyrosinase. Physiological implications. AB - Murine melanoma melanosomal tyrosinase, solubilised at pH 6.8 and 1% Igepal, exhibits a lag in cresolase activity which increases with increasing concentration of tyrosine. The enzyme, solubilised at pH 5.0 and assayed at pH 5.0, does not exhibit lag even at inhibitory concentrations of tyrosine while the same enzyme when assayed at pH 6.8 exhibits characteristic lag. When the enzyme was solubilised from a melanosomal fraction with detergent/water without any buffer, significant linear activity for 2 h was seen at an inhibitory concentration of tyrosine, indicating for the first time the presence of a form of tyrosinase without lag and inhibition by excess tyrosine. Exposure of the enzyme solubilised in buffer/detergent at pH 6.8 to rapid decrease in pH to 5.0 or 4.7 makes the enzyme remain irreversibly in the form without characteristic lag, even at an inhibitory concentration of tyrosine and at pH 6.8. These results may be interpreted as follows. The enzyme at pH 6.8 exists in the E form with an allosteric site for tyrosine. Decrease of the pH of the enzyme solution from 6.8 to 5.0 or 4.7 by dialysis results in the reversible protonation of the enzyme, which no longer binds tyrosine at its allosteric site and consequently inhibition by excess tyrosine and lag were not observed at acidic pH. However, if the enzyme was rapidly brought to pH 5.0 from 6.8 it remains irreversibly in the protonated form even at pH 6.8. Ascorbic acid acts as an effective reductant for the hydroxylation of tyrosine by tyrosinase, while 3,4-dihydroxyphenylalanine is both an effective reductant and counteracts the inhibition by tyrosine at pH 6.8. PMID- 3111849 TI - Chemical modification of phosphorylase b by tetranitromethane. Identification of a functional tyrosyl residue. AB - Tetranitromethane, C(NO2)4, a reagent for tyrosyl residues, was found to inactivate irreversibly rabbit skeletal muscle glycogen phosphorylase b. Under the chosen conditions seven tyrosyl residues, namely Tyr-75, 203, 262, 280, 403, 552 and 647, were found to be nitrated. Inactivation was prevented by the presence of the allosteric activator 5'-AMP during nitration. Under these latter conditions one of the reactive tyrosyl residues was not modified by C(NO2)4; thus, this residue appeared to be essential for either catalytic activity or allosteric activation. Tryptic digests of phosphorylase b, reacted with C(NO2)4 in the absence and presence of 5'AMP, were fractionated by gel filtration. The peptide mixtures were further purified by reverse-phase HPLC. One of the peptides contained the tyrosyl residue which was modified by C(NO2)4 only in the absence of 5'AMP. The sequence of this peptide was determined. The amino acid residue which is responsible for the loss of activity upon reaction with C(NO2)4 was identified in the amino acid sequence of phosphorylase b as tyrosine-75. Of the other residues modified in the presence and in the absence of C(NO2)4, tyrosine 403 contributes to the glycogen-storage site whereas Tyr-280 is close to the alpha-D-glucose-binding site. These residues, exposed to the solvent both in the presence and in the absence of 5'AMP, are not essential for catalytic activity. PMID- 3111851 TI - Type VI collagen represents a major fraction of connective tissue collagens. AB - A new method for the isolation of type VI collagen from peptic tissue digests is presented which gives tenfold higher yields than methods previously reported. From the amounts of purified protein obtained from human placenta, bovine uterus, chicken gizzard and entire mouse bodies we conclude that type VI collagen represents a major fraction of connective tissue collagens. PMID- 3111853 TI - Long-term follow-up of incessant supraventricular tachycardia treated with oral encainide. AB - The long-term follow up (32 to 44 months, mean 37 months) of 9 patients with incessant supraventricular tachycardia treated with oral encainide is reported. During that follow up period, 1 patient developed an 'escape' phenomenon to encainide and incessant supraventricular tachycardia recurred in spite of increasing doses of encainide. Two patients required electrical fulguration of the bundle of His because of inability to control incessant supraventricular tachycardia. One patient discontinued treatment without suffering from recurrences of the arrhythmia. In 6 of the original 11 patients treated with oral encainide, antiarrhythmic efficacy persisted after a mean of 3 years. No additional long-term side effects developed. It is concluded that the antiarrhythmic efficacy of oral encainide in incessant supraventricular tachycardia persists long-term, although some patients may develop an 'escape' phenomenon to encainide while others develop spontaneous cure of tachycardia. PMID- 3111854 TI - Short-lived isotopes in central chemical control of ventilation. AB - Central chemical ventilatory drive is dependent on electrolyte and acid-base status of brain ECF, as well as the interaction between H+ metabolism and CO2 fixation and metabolism of amino acid neurotransmitters-GABA and glutamate. In the anesthetized dogs, using the short-lived positron emitting isotope of carbon (11C) either in the form of molecular CO2 or as HCO3- injected intraarterially it was demonstrated that there is first pass uptake of 16% of HCO3- from blood into brain and 86% uptake of molecular CO2, thus indicating that the brain-blood barrier is permeable to HCO3-, but that HCO3- content in the CNS is regulated as a function of dissociation of strong ions such as Cl- and Na+. Relationship between CO2 fixation and brain glutamine was studied with intraarterial injection of 13N-ammonia and its turnover into glutamine when PCO2 was increased. Ammonia turnover into glutamine was increased by a factor of 2 when PaCO2 was increased by 35 torr, and this rise in glutamine was linearly related to the rise in CSF [HCO3-]. Glutamine is then converted into the active neurotransmitters GABA and glutamate. Thus, the short-lived isotopes allow for assessment of the interaction of biochemical events in the CNS in the central respiratory drive. PMID- 3111855 TI - Effect of submandibular gland removal on carcinogen induced rat mammary tumors. PMID- 3111856 TI - Modulation of expression of class II histocompatibility antigens by secretion of a cellular inhibitor in K562 leukemic cells. AB - In this report we show that it is possible to induce the expression of HLA-DR antigens on K562 cells, previously reported to be unresponsive to interferon gamma (IFN-gamma). However, only low cell concentrations and a high dose of IFN gamma allowed the induction of HLA-DR antigens. Furthermore, the recombinant glycosylated IFN-gamma is 100-fold more efficient than the unglycosylated form. This induction of HLA-DR antigens on K562 was not related to a stage of differentiation or to the presence of cells subsets specifically sensitive to IFN gamma, since repeated sorting of K562 HLA-DR-positive and negative cells did not lead to the selection of a cell subset with a different potential of induction for HLA-DR. The difficulty in obtaining induction is due to the production of a soluble endogenous inhibitor of proteic nature, whose action is not restricted to the K562 cell line since it operates also on both epithelial and fibroblastic cells. Treatment of normal human epithelial and fibroblastic cells with conditioned medium from K562 cultures caused a marked decrease in the expression of HLA class II antigens (DR and DP) induced by IFN-gamma (10,000 U/ml), but had no effect on cell growth; however, it also affected expression of HLA class I antigens. This inhibition is not mediated by prostaglandin or an IFN-alpha or IFN beta-dependent mechanism. Production of this inhibitor by pluripotent human leukemic cells could cause an unbalance in the complex control exerted by the immunological system during hematopoietic differentiation or leukemic progression. PMID- 3111858 TI - Lysis of nonnucleated red blood cells by cytotoxic T lymphocytes. AB - To establish the role of direct membrane damage in cytotoxic T lymphocytes (CTL) mediated lysis we investigated whether CTL would be capable of lysing nonnucleated target cells. By antibody-mediated targeting we show that CTL are indeed capable of lysing sheep and human red blood cells. PMID- 3111857 TI - Immunoglobulin heavy chain gene diversification in the long-term bone marrow culture of normal mice and mice with severe combined immunodeficiency. AB - The change of immunoglobulin heavy (H) chain gene configuration during the differentiation of B cells from their early precursors was investigated in long term cultures of bone marrow cells (LTBC). Hemopoietic stem cells are maintained in LTBC described by Dexter et al. (J. Cell. Physiol. 1977. 91: 335; LTBC-D), which supports the differentiation of myeloid lineage cells but not B lineage cells. By simply shifting the culture condition to that devised by Whitlock and Witte (Proc. Natl. Acad. Sci. USA 1982. 79: 3608; LTBC-B) to support the development of B lineage cells, surface IgM-bearing (sIgM+) B cells became detectable by the 2nd week after the shift and the number quickly increased thereafter, while the number of polymorphonuclear cells and granulocyte macrophage colony-forming cell (CFU-c) decreased rapidly. H chain gene configuration of the developing cells in the culture was examined by Southern blot analysis of Eco RI-digested DNA with a JH probe. Whereas rearranged JH gene configuration was not detectable in the DNA from LTBC-D cells, it first appeared 2 weeks after the shift, and the level of the rearrangement rapidly increased thereafter as the intensity of JH band of germ-line configuration decreased. Almost all the cells in the culture had undergone H chain gene rearrangement in both chromosomes by the 6th week after the shift. During 2 to 4 weeks after the shift, a cluster of bands spanning around 4.5-5.5 kb appeared dominant among the rearranged configurations of JH gene and then it decreased in intensity as the pattern of JH band became a more homogeneous smear. The distribution of rearranged JH bands observed during 3-4 weeks after the shift was strikingly similar to that observed in normal spleen B cells. By semi-quantitative analysis of the intensity of JH and DSP2 bands remaining in germ-line configuration, it was found that the loss of germ-line JH band was far more rapid than that of germ line DSP2 bands in the developing B cells in vitro. This result is consistent with the conclusion obtained in B cell tumor lines that D to J assembly occurred first and was followed by V to DJ assembly in this culture system. Taken together, it is likely that the process of H chain gene diversification in this culture system may represent the actual process during B cell differentiation in vivo. Differentiative capacity of bone marrow stem cells from mouse with severe combined immunodeficiency (SCID) was also analyzed in the same culture system.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3111859 TI - Curing BB rats of freshly manifested diabetes by short-term treatment with a combination of a monoclonal anti-interleukin 2 receptor antibody and a subtherapeutic dose of cyclosporin A. AB - The BioBreeding (BB) rat develops spontaneously a syndrome resembling human type I diabetes mellitus. The short-term treatment of newly diagnosed diabetic BB rats with the anti-interleukin 2 receptor (IL 2R) monoclonal antibody ART-18 in combination with a subtherapeutic dose of cyclosporin A for 10 days, a treatment shown previously to eliminate specifically antigen-activated IL2R+ T lymphocytes by sparing suppressor cells, resulted in normoglycemia in 70% of the animals, the maintenance of B cell volume density and an increase in pancreatic insulin content. Moreover, the glucose tolerance of successfully treated animals was not significantly different from that of normoglycemic BB rats during the whole observation period (up to 120 days after the end of the therapy). This is the first report on successful treatment of a spontaneous autoimmune disease by a short-term and specific immunosuppressive regimen with limited side effects. PMID- 3111860 TI - "In vivo" activated splenic T cells are refractory to interleukin 2 growth "in vitro". AB - Naturally activated T lymphocytes present in normal mouse spleen were studied for direct reactivity to interleukin 2 (IL 2) and for binding of anti-IL 2 receptor (IL 2R) antibodies or radiolabeled IL 2. The majority of large-sized splenic T lymphocytes are IL 2R-; thus, at the most one third of large L3T4+ T cells and of large Lyt-2+ T lymphocytes bind (weakly) anti-IL 2R antibodies; furthermore, most IL 2R+ cells in the normal spleen are actually Lyt2-, L3T4-. Total large splenic lymphocytes do not express more than an average of 150 high-affinity IL 2R/cell. Such cell populations, as well as large T cells enriched from them, failed to proliferate exponentially in the presence of recombinant IL 2, but did not suppress the IL 2-dependent proliferative responses of small T cells activated in the same cultures. In vivo activation of small T cells, in concanavalin A-treated irradiated syngeneic hosts, also results in refractoriness to growth in recombinant IL 2. In addition, these cells remain insensitive to ligands such as concanavalin A, phorbol myristate acetate and ionomycin, in the presence or absence of IL 2. These results question the role of IL 2 as a growth factor of in vivo activated splenic T lymphocytes, or else indicate that most of these are terminally differentiated cells. PMID- 3111861 TI - Phenotype of stromal cell-associated thymocytes in situ is compatible with selection of the T cell repertoire at an "immature" stage of thymic T cell differentiation. AB - Murine thymocytes interacting with cortical macrophages, cortical epithelial cells and medullary dendritic cells in situ express T cell receptors at low to intermediate density. They co-express the lineage markers Lyt-2 and L3T4 and are not enriched for cells expressing high-density interleukin 2 and lymph node homing receptors. Thus, recognition of stromal cells in situ in distinct thymic microenvironments occurs at a common stage of T cell maturation which is phenotypically intermediate between intrathymic precursor cells and mature medullary-type thymocytes. The surface phenotype of dendritic cell-associated thymocytes indicates the presence of thymocytes with a "cortical" phenotype within the antigen-exposed ("nonsterile") phase of T cell maturation in the medulla. PMID- 3111862 TI - Alternative pathway of complement activation by stimulated T lymphocytes. I. Binding of C3 fragments. AB - Human blood lymphocytes cultured for 3 days with concanavalin A (Con A), phytohemagglutinin or pokeweed mitogen, in mixed lymphocyte culture with added interleukin 2 and stimulated by a lymphoblastoid cell line were found to activate and bind C3 molecules when exposed to human serum. The split products of C3 were detected in the supernatants and on the surface of the activated cells. The surface-attached C3 fragment on the Con A blast was identified as C3b by immune adherence i.e. binding of CR1 carrying human erythrocytes. In the Con A stimulated population the majority of cells that activated and bound C3 were CD3 and Fc gamma receptor (CD16)-positive but complement receptor-negative blasts. In this cell subset both CD4 and CD8-positive cells were detected but their frequency suggested that a proportion of them carried both markers. PMID- 3111863 TI - Alternative pathway of complement activation by stimulated T lymphocytes. II. Elevation of cytotoxic potential against complement receptor-carrying cell lines. AB - Exposure of lectin-stimulated (concanavalin A, phytohemagglutinin and pokeweed mitogen) blood lymphocytes to human serum or to purified C3 increased their cytotoxic capacity towards complement receptor positive targets such as Raji and Daudi cells. The lysis of complement receptor-negative lymphoblastoid cell lines was not influenced. The lytic capacity of lymphocytes exposed to 12-O tetradecanoylphorbol 13-acetate was not elevated by human serum. Lectin stimulated lymphocytes were previously shown to activate and bind C3. The results using lymphocytes activated in different ways and targets with or without complement receptor expression suggest that the C3b deposited on lymphocytes binds to the complement receptor on the targets. This contact elevates the avidity between the two cells as indicated also by the increased frequency of the lymphocyte-target conjugates. On the basis of immune adherence the C3 fragment bound on the lymphocytes was identified as C3b. The increase of the conjugate formation and cytotoxicity was abrogated when the target cells, Raji, were pre exposed to purified C3d which occupy the CR2 receptor. The majority of lymphocytes responsible for the cytotoxicity were CD8+. PMID- 3111864 TI - The role of the diacylglycerol-protein kinase C system in mediating adrenoceptor prostacyclin synthesis coupling in the rat aorta. AB - The role of the diacylglycerol-protein kinase C system in mediating adrenoceptor stimulated prostacyclin (PGI2) synthesis in the isolated rat aorta was investigated using the diacylglycerol-mimetic phorbol 12,13-dibutyrate (PDBU) and the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperizine (H7). PDBU stimulated rat aortic PGI2 synthesis in a dose-dependent manner, an action potentiated by adrenaline and the calcium ionophore A23187. EDTA (10(-2) mol X l-1) completely inhibited PDBU-stimulated PGI2 synthesis. The calcium channel blockers, verapamil and nifedipine, inhibited PDBU-stimulated PGI2 synthesis in a dose-dependent manner, as did the protein kinase C inhibitor H7. The adrenoceptor antagonists phentolamine, prazosin and yohimbine were without effect on PDBU-stimulated PGI2 synthesis. H7 also inhibited adrenaline stimulated, but not trauma-, A23187- or arachidonate-stimulated PGI2 synthesis. These experiments constitute evidence that adrenoceptor-PGI2 synthesis coupling is mediated by diacylglycerol-protein kinase C initiation of calcium influx in the rat aorta. PMID- 3111865 TI - Mechanisms of arachidonic acid-induced contractions of canine cerebral arteries. AB - The effects of arachidonic acid in cerebral blood vessels has been examined using rings of canine cerebral arteries. Arachidonic acid produced dose-dependent contractions of this preparation even after mechanical removal of the endothelium. The contractions were not blocked by indomethacin or acetylsalicylic acid, both of which inhibit cyclooxygenase, but were inhibited by nordihydroguaiaretic acid which is a lipoxygenase inhibitor, BW 755c which blocks both pathways, and FPL 55712 which is an antagonist at leukotriene receptors. These data imply that arachidonic acid-induced contractions are mediated by products of the lipoxygenase pathway. Leukotrienes and cyclooxygenase products are generated by this preparation as shown by HPLC and radioimmunoassay and both LTC4 and LTD4 produce contractions in cerebral arteries lending further evidence in support of this suggestion. PMID- 3111867 TI - Decarboxylation of DL-2,4-dihydroxyphenylalanine (2,4-DOPA) to 2,4 dihydroxyphenylethylamine in mouse striatal slices. AB - Decarboxylation of an unnatural analogue of DOPA by brain aromatic amino acid decarboxylase was measured by HPLC with electrochemical detection. Incubation of striatal slices with DL-2,4-dihydroxyphenylalanine (2,4-DOPA) resulted in biosynthesis and accumulation of 2,4-dihydroxyphenylethylamine, which was completely blocked by carbidopa. 2,4-DOPA induced a significant decrease in endogenous dopamine, but the loss was not prevented by carbidopa. Since 2,4-DOPA is a potential pro-drug for melanoma chemotherapy, further evaluation of its neurobiologic properties is needed. PMID- 3111866 TI - Further evidence that noradrenaline is not involved in the anti-immobility activity of chronic desipramine in the rat. AB - The effect of 10 mg/kg per day desipramine for 7 days on performance in the forced swimming test was studied in rats given various treatments aimed at reducing central noradrenergic transmission. 6-Hydroxydopamine-induced destruction of noradrenaline-containing neurons originating in the locus coeruleus or ascending in the ventral bundle had no effect on the anti-immobility activity of desipramine. Likewise, no changes in the effect of desipramine were seen with an intraperitoneal injection of DSP-4 (50 mg/kg) which destroyed brain noradrenergic neurons, particularly those of the dorsal bundle ascending to the forebrain. The results argue against a role of noradrenaline in the mechanism by which repeated treatment with desipramine reduces the immobility of rats in the forced swimming test. PMID- 3111868 TI - Interaction between chloroquine and indomethacin in airways smooth muscle in vivo. AB - The indomethacin-induced enhancement of airways smooth muscle contractility to histamine reported earlier in vitro has now been demonstrated in conscious guinea pigs. Chloroquine, an anti-malarial drug with phospholipase A2 inhibitory activity, antagonized histamine and also reversed the indomethacin-induced enhancement. These observations indicate that histamine-induced bronchospasm in vivo is modulated by the arachidonate system and that chloroquine-type phospholipase A2 inhibitors may ameliorate such bronchospasm. These findings also explain the observed clinical benefits of chloroquine in chronic asthmatics. PMID- 3111871 TI - Microbiological monitoring in inbred mouse foundation stocks in Japan. AB - Microbiological monitoring on 128 inbred mouse foundation stocks consisted of common 10 inbred strains and inbred strains originated from outbred dd mice was performed by cooperation of 24 organizations. A total of 881 mice were divided into 647 conventional animals from 95 colonies and 234 barrier-sustained animals from 33 colonies. Three viral, one mycoplasmal, 6 bacterial, one fungal and 3 parasitic agents selected as monitoring microbes according to the proposed selection standards. Among conventional colonies, 84.2% were positive for at least one agent. The highest detection rate was 44.2% for S. obvelata, followed by P. pneumotropica and S. muris, P. aeruginosa, G. muris, Sendai virus, M. pulmonis, MHV and E. coli O115a, c: K (B). Of these agents, only one microbe, P. aeruginosa, was detected in barrier-sustained colonies (36.4%), thus the efficacy of barrier system for the microbiological quality control of the inbred mouse foundation stocks was actually demonstrated. The positive rates of MHV (6.3%) and Sendai v. (16.8%) were significantly low compared with those in experimental mouse colonies. Positivity for parasites was rather high and they were infested together with other pathogens in many cases. Thus parasites including G. muris, S. muris and S. obvelata were regarded as useful indicators to see microbiological contaminations in conventional mice. There observed no strain difference in susceptibility to pathogens except for C57BL/6 and AKR mice which seemed to be high antibody responders to MHV. PMID- 3111869 TI - A phorbol ester inhibits the release of endothelium-derived relaxing factor. AB - The effect of the phorbol ester phorbol-12,13-dibutyrate (PDB), an activator of protein kinase C, on endothelium-dependent relaxation was studied in noradrenaline-constricted isolated aortic ring preparations of the rabbit. Endothelium-dependent relaxation induced by acetylcholine or substance P was inhibited by PDB (greater than or equal to 10(-7) M). Endothelium-dependent relaxation induced by the calcium ionophore A23187 (7.5 X 10(-8) and 10(-7) M) was unaffected by PDB (to 10(-6) M). The mechanical responses to acetylcholine or sodium nitroprusside in endothelium-denuded rings were not altered by PDB (to 10( 6) M). The results suggest a role for protein kinase C in receptor-mediated EDRF release mechanisms. PMID- 3111870 TI - Pharmacological modulation of bradykinin-, acetylcholine- and calcium ionophore A23187-induced relaxation of rabbit pulmonary arterial segments. AB - Bradykinin (BK; 10(-10)-10(-7) M) relaxes phenylephrine-contracted rabbit isolated pulmonary arterial rings. The mechanical destruction of the endothelial layer obliterates acetylcholine (ACh) and A23187-induced relaxation without influencing BK-, isoproterenol-, sodium nitroprusside- and papaverine-induced relaxations. Atropine and propranolol selectively antagonized ACh- and isoproterenol-induced relaxation, respectively, without influencing BK-induced relaxation. Indomethacin (1.4 X 10(-5) M, a potent cyclooxygenase inhibitor, 30 60 min) and p-bromophenacylbromide (5 X 10(-6) M, p-BPB, a potent phospholipase A2 inhibitor, 30-60 min) selectively inhibited BK-induced relaxation without influencing relaxation to isoproterenol, sodium nitroprusside and papaverine. These data suggest that BK stimulates PLA2 and releases arachidonic acid (AA), which is further metabolized via cyclooxygenase and prostaglandin synthetase to prostacyclin (PGI2), causing relaxation of rabbit pulmonary arterial segments. The inhibition of ACh- and A23187-induced relaxation by p-BPB, but not by indomethacin, suggest that initial activation of PLA2 causes the release of AA, which is subsequently metabolized to endothelial-derived relaxant factor (EDRF; lipid peroxides, ROOH, ROO-?). PMID- 3111872 TI - Synthetic antiprogestins stimulate human granulosa cell estradiol production in vitro. AB - The effect of synthetic antiprogestins, RMI 14156 and STS 557, on gonadotrophin stimulated estradiol (E2) production in human ovarian granulosa cells (GC) has been tested in vitro, to see if by virtue of their antiprogestational activity these compounds would promote the production of E2, and thereby follicular growth. Granulosa cells from human ovaries were cultured in modified minimum essential medium with or without luteinising hormone (LH, 10 ng/ml), follicle stimulating hormone (FSH, 100 ng/ml), androstenedione (A, 10(-7) M), RMI 14156 (10(-9) M-10(-5) M) and STS 557 (10(-9) M-10(-5) M), in a humidified 95% air 5% CO2 atmosphere at 37 degrees C for 48 hours. RMI 14156 and STS 557 were found to stimulate the production of E2 by cultured human GC in a dose dependent manner, the stimulation being significant (P less than 0.001-P less than 0.05) at higher doses (10(-6) M, 10(-5) M). The two antiprogestins used also stimulated the gonadotrophin induced E2 production significantly. Results demonstrated that these synthetic antiprogestins, having an 'estra' type of basic structure RMI 14156 17 beta hydroxy-7 alpha-methyl-5-estra-en-3-one); STS 557 (17 alpha cyanomethyl-17 beta-hydroxy-estra-4,9(10)diene-3-one) can directly promote E2 production from human ovarian GC in vitro. PMID- 3111873 TI - The prolactin response to TRH and domperidone does not differentiate male hypothalamic hypogonadism and constitutional delay of puberty. AB - In order to test whether prolactin response to challenge with TRH and domperidone, dopamine receptor antagonist, is diagnostic for idiopathic hypothalamic hypogonadism (IHH) we studied 8 normal controls, 9 subjects with delayed sexual development and 6 patients with IHH. TRH test (200 micrograms i.v. bolus) and domperidone (10 mg i.v. bolus) were given on two different days. Prolactin (RIA-Biodata) was determined in blood samples during the test. The basal value of prolactin in subjects with delayed puberty and healthy controls did not differ from basal values of prolactin in patients with IHH. The peak elevation of prolactin after TRH in subjects with delayed puberty and healthy controls did not differ from that in patients with IHH. After successful treatment of one patient with IHH (Kallmann's syndrome) with pulsatile s.c. LHRH we did not find any change in the response of prolactin to TRH challenge after 1, 3 and 6 months of treatment, while prolactin response to domperidone increased. Prolactin responses to TRH and domperidone are not differential for the early diagnosis of IHH. Successful treatment of a patient with IHH did not change the response of prolactin to TRH, but increased prolactin response to domperidone possibly due to altered steroid milieu. PMID- 3111875 TI - Chylous pleural effusion as the initial manifestation of Waldenstrom's macroglobulinemia. PMID- 3111874 TI - Depressed cellular immunity in Mycoplasma pneumoniae pneumonia. AB - We studied the lymphocytes and serum suppressive factor in patients with Mycoplasma pneumoniae pneumonia. Skin testing for delayed hypersensitivity to tuberculin was performed in 44 patients with pneumonia associated with M. pneumoniae infection. These patients were tuberculin-positive. Twenty-five patients showed a transient negative tuberculin reaction in the acute stage and 19 had a positive reaction. In tuberculin-negative patients, peripheral blood T lymphocytes were not significantly reduced; however, the blastogenic lymphocyte response to purified protein derivative (PPD) and PPD-induced gamma-interferon production were significantly reduced when compared with those in tuberculin positive patients and healthy tuberculin-positive controls. The lymphocyte response of healthy tuberculin-positive controls was not suppressed by adding the serum of the tuberculin-negative patients. These results suggest that tuberculin anergy in patients with M. pneumoniae pneumonia early after clinical onset is due to depressed lymphocyte functions and not to serum factors. PMID- 3111876 TI - Schistosoma mansoni: chemical stabilization of cercariae by aldehydes. AB - Chemically stabilized cercariae of Schistosoma mansoni have been developed by inactivating surface glycoproteins which are essential for their survival. The inactivation was achieved by reaction with 0.01-0.1% glutaraldehyde, 0.1-1% formaldehyde, and 0.37-3.7 microliters citraconic anhydride. The cercariae lost their viability but retained the ability to exclude trypan blue for up to 2 years in a manner similar to live cercariae and in contrast to cercariae killed by other means, which took up the dye immediately. The chemically stabilized cercariae reacted with polyclonal and monoclonal antischistosome antibodies in an indirect immunofluorescence assay for up to 2 years, indicating the retention and preservation of surface antigens. Chemically stabilized cercariae revealed the presence of antischistosome antibodies as early as 1 week after infection when used for immunodiagnosis of mouse and rat infections. The presence of Fc receptors for human IgG on the stabilized cercariae interfered in their use as an immunodiagnostic reagent of human schistosomiasis. The stabilized cercariae were also used to screen cultures for monoclonal antischistosome antibodies. Preliminary results indicated that immunization of mice with glutaraldehyde stabilized cercariae imparted protective immunity to mice. PMID- 3111877 TI - Ultrastructural analysis of the anti-chlamydial activity of recombinant murine interferon-gamma. AB - The effect of murine interferon-gamma (MuIFN-gamma) on the developmental cycle of Chlamydia trachomatis in McCoy cells was analyzed by light and electron microscopy. Addition to the culture media of 10 ng/ml of MuIFN-gamma, either 24 hr before or immediately after Chlamydia infection, resulted in a significant inhibition of the growth of this organism. Microscopic analysis showed that with both treatments the majority of microorganisms were arrested at the elementary body stage. Only a few small chlamydial inclusions were detected at 48 hr postinfection and contained predominately reticulate bodies. Furthermore, the growth of Chlamydia was arrested in cells that were treated with MuIFN-gamma at various intervals following infection. Addition of MuIFN-gamma at 8 or 12 hr after infection resulted in the arrest of chlamydial growth before initiation of reticulate body fission. When the MuIFN-gamma was added 24 hr postinfection, we could detect, by electron microscopy, inhibition at the stage of reticulate body replication. PMID- 3111878 TI - Aflatoxin B1 and acetaminophen induce different cytoskeletal responses during prelethal hepatocyte injury. AB - Primary monolayer cultures of adult rat hepatocytes exposed to the hepatocarcinogen aflatoxin B1 (AFB1) undergo a characteristic prelethal cytomorphological change that is distinct from their response to the necrogenic noncarcinogenic hepatotoxin, acetaminophen (AAP). Since changes in cell shape are mediated, at least in part, by the F-actin cytoskeleton, we designed experiments to study early prelethal alterations in the distribution of actin microfilaments in monolayer rat hepatocytes exposed to AFB1 (100 microM) or AAP (16 mM). Using rhodamine-phalloidin fluorescence microscopy, we observed that normal hepatocytes showed a submembranous F-actin distribution with focal short microfilaments extending into filopodia along the periphery of the cell. Hepatocytes exposed to AFB1 for several hours exhibited retraction of their cytoplasm within a prominent circumferential peripheral band of F-actin microfilament bundles. Retraction of focal areas of peripheral cytoplasm was associated with an increased prominence of the radial F-actin-containing filopodia. Subsequently, there appeared peripheral blebs containing very little F-actin. Hepatocytes exposed to equivalently lethal concentrations of AAP initially remained structurally normal. After several hours, the cells exhibited a prominent polar aggregate of short microfilament bundles without the formation of blebs. Both the blebbing and the polar aggregation of F-actin bundles occurred prior to cell death as shown by lactate dehydrogenase release and trypan blue exclusion. These studies support the hypothesis that the lethal effects of these two agents may occur by different biological mechanisms that are associated with remarkably distinct prelethal cytoskeletal responses. PMID- 3111879 TI - Effect of ovariectomy on response to dietary cholesterol in patas monkeys (Erythrocebus patas). AB - From a group of 20 patas monkeys (Erythrocebus patas), four high and four low responders to dietary cholesterol were selected for this study. The monkeys were paired according to their responsiveness to cholesterol, and ovariectomies were carried out on one group of the matched pairs. For the study, the monkeys were fed a Prudent Diet (at 0.1 mg cholesterol/cal) for 5 months preceding the ovariectomy and for 7 months after the ovariectomy followed by a Rich Diet (at 0.4 mg cholesterol/cal) for 7 months. Serum cholesterol, apo B, and apo A-I concentrations and cholesterol distributions were determined. We observed that while the monkeys consumed the Prudent Diet, total serum cholesterol. HDL cholesterol, and apo A-I increased in the ovariectomized group, but not in the control group. When they began consuming the Rich Diet, total serum cholesterol, apo B, and apo A-I concentrations increased in all monkeys, but increased more in the ovariectomized monkeys. The effect of the loss of ovarian function on lipoprotein metabolism is accentuated when the monkeys are fed a Rich Diet designed to be similar to a saturated fat, cholesterol-rich diet consumed by human beings. PMID- 3111881 TI - Plasmid deoxyribonucleic acid in throat and cerebrospinal fluid isolates of Neisseria meningitidis. AB - Ten strains of Neisseria meningitidis, isolated either from cerebrospinal fluid or from throat cultures, were typed and screened for the presence of plasmid DNA. Three group C strains, isolated in the same area, each harboured a plasmid of similar molecular weight (approx. 8.5 Md). No evidence of plasmid DNA was found in the other strains (whether of the same group but isolated in another area, or of other groups). PMID- 3111880 TI - Anticonvulsant drugs in monotherapy. Effect on the fetus. AB - We describe a material of 577 infants born of epileptic women treated with anticonvulsants in monotherapy during early pregnancy and collected from France, Italy, and Sweden. The incidence of major malformations is increased compared with the general population but no definite difference in risk can be demonstrated between the various anticonvulsants, but valproic acid was associated with a doubling of the average risk. The increased risk for facial clefts and for cardiac malformations, described from most studies on epilepsy during pregnancy, cannot be seen in this material. Unusually many cases of penis abnormalities (micropenis, hypospadias) were noted. An effect on fetal growth can be demonstrated and is apparently more pronounced for carbamazepine than for the other drugs. It results in a reduced birth weight in spite of normal gestational length, reduced body length and head circumference. The possible biological significance of this finding is discussed. PMID- 3111882 TI - [Effect of antioxidants on the activity of liver glutathione-S-, glucuronyl- and sulfurtransferases in rats]. AB - It was shown that pretreatment of rats with antioxidants (AO) butylhydroxytoluene and 2-ethyl-6-methyl-3-hydroxypyridine hydrochloride owing to its effect of animal protection against intoxication with diethylnitrosamine (DENA) increases the liver activity of enzymes of stage II metabolism of xenobiotics: glutathione S-transferase (GST), UDP-glucuronyltransferase (UDP-GT). Administration of DENA (LD50) produced a significant decrease of the activity of GST and UDP-GT as compared with that in intact animals. At the same time its action on the animals pretreated with AO develops against the background of increased activity of these enzymes. PMID- 3111883 TI - Identification and purification of a novel G protein from neutrophils. AB - A novel G protein which appears to couple chemotactic peptide receptors to a polyphosphoinositide phospholipase C has been purified from rabbit neutrophils. Neutrophil membranes were solubilized with sodium cholate and fractionated by successive anion exchange, gel filtration and hydrophobic chromatography. Guanosine-5'-(3-O-thio)triphosphate binding activity was purified 170-fold from the soluble extract. The alpha-subunit of the purified G protein was identified by pertussis toxin-catalyzed ADP-ribosylation, and found to have an Mr of 40,000. The beta-subunit (Mr 36,000) comigrated on SDS-polyacrylamide gel electrophoresis with the beta-subunits of bovine brain Gi and Go. The neutrophil pertussis toxin substrate is highly unstable in cholate solution unless 30% ethylene glycol is added. Structural and functional analysis of this novel G protein will advance our understanding of the molecular mechanisms of coupling of receptors to phospholipase C. PMID- 3111884 TI - Ethanol alters the adenosine receptor-Ni-mediated adenylate cyclase inhibitory response in rat brain cortex in vitro. AB - It has been suggested that ethanol stimulates adenylate cyclase in vitro through an increased function of Ns, the activatory component of adenylate cyclase. Because of the interaction of Ns with Ni, the adenylate cyclase inhibitory component, we have studied the effect of ethanol (0.05-0.2 M) on Ni-mediated adenylate cyclase inhibition caused by the adenosine analog N6 phenylisopropyladenosine (N6-PIA) in brain cortical membranes. Ethanol did not alter N6-PIA binding to the adenosine Ri-receptors, stimulated slightly basal adenylate cyclase activity but abolished adenylate cyclase inhibition due to N6 PIA, suggesting an effect of ethanol on the inhibitory coupling pathway. This was further supported by loss of the adenylate cyclase inhibitory response to GTP (greater than 10(-5) M). It thus seems that, besides its effect on the Ns system, ethanol may also impair Ni-mediated adenylate cyclase responses in rat cerebral cortex. PMID- 3111885 TI - Oxidation of N-alkyl and C-alkylputrescines by diamine oxidases. AB - N-Methyl-, N-ethyl-, N-propyl- and N-butylputrescine were assayed as substrates of diamine oxidase from pea seedling and pig kidney. With the exception of N methylputrescine they were found to be oxidized to the corresponding aminoaldehydes. 1-Methyl-, 2-methyl-, 1-ethyl- and 1-propylputrescine were oxidized by the oxidases at lower rates than the N-alkylderivatives. 1,3 Dimethylputrescine had negligible oxidation rates while 1,4-dimethylputrescine (2,5-diaminohexane) was not a substrate. The oxidation of putrescine by the kidney oxidase was inhibited by 1,4-dimethylputrescine, while the pea oxidase was strongly inhibited by the former as well as by 2-methylputrescine and 1,3 dimethylputrescine. Serum amine oxidase did not oxidize the substituted putrescines although several of the latter inhibited spermidine oxidation by this oxidase. PMID- 3111886 TI - Aldose reductase and p-crystallin belong to the same protein superfamily as aldehyde reductase. AB - Aldose reductase (EC 1.1.1.21) has been implicated in a variety of diabetic complications. Here we present the first primary sequence data for the rat lens enzyme, obtained by amino acid and cDNA analysis. We have found structural similarities with another NADPH-dependent oxidoreductase: human liver aldehyde reductase (EC 1.1.1.2). The identity between these two enzymes is 50%. Both enzymes share approx. 40-50% homology with p-crystallin, a major lens protein present only in the frog, Rana pipiens. We propose that aldose reductase, aldehyde reductase and p-crystallin are members of a superfamily of related proteins. PMID- 3111887 TI - Heterogeneous glycosylation of the EXG1 gene product accounts for the two extracellular exo-beta-glucanases of Saccharomyces cerevisiae. AB - Two exo-beta-glucanases of glycoprotein nature can be detected in culture supernatants of Saccharomyces cerevisiae cells. These exo-beta-glucanases show different Mr values and kinetic properties, although they are immunologically related. Their carbohydrate content and the electrophoretic mobility of both endoglycosidase H-treated exo-beta-glucanases suggest that they share the same protein fraction. Studies at genetic level relate the production of both extracellular exo-beta-glucanases with the expression of a single-copy gene in S. cerevisiae. Expression of this gene in another yeast, Schizosaccharomyces pombe, demonstrates that it codes for a protein with exo-beta-glucanase activity whose heterogeneous N-glycosylation accounts for both extracellular exo-beta-glucanases of S. cerevisiae. PMID- 3111888 TI - Interaction of iodinated vinculin, metavinculin and alpha-actinin with cytoskeletal proteins. AB - Iodinated vinculin, metavinculin and alpha-actinin were used to probe the interaction of these proteins with electrophoretically separated cytoskeletal proteins. Using the gel overlay technique, we detected strong binding of 125I vinculin and 125I-metavinculin to alpha-actinin, 175 kDa polypeptide, talin, vinculin and metavinculin themselves, and moderate binding to actin. 125I-alpha actinin was capable of interacting with vinculin and metavinculin. The specific binding of 125-I-alpha-actinin to vinculin and metavinculin immobilized on a polysterene surface was also demonstrated. We suggest that the ability of vinculin and alpha-actinin to form a complex may be realized in microfilament membrane linkages. PMID- 3111889 TI - Highly potent and specific inhibitors of human renin. AB - We have designed and synthesized a series of small peptides containing a perfluoroalkyl ketone group at the C-terminal position of the angiotensin I sequence as inhibitors of human renin. From this series of compounds, 8 and 10 showed strong inhibition of human renin (IC50 = 3 X 10(-9), 7 X 10(-9) M, respectively). Compound 10 did not inhibit pepsin and cathepsin D at 10(-4) M. Comparison of the IC50 of compound 8 and compound 11 (8.7 X 10(-7) M) demonstrated the marked effect of the perfluoropropyl group on the potency of inhibition on renin, presumably due to the strong electron-withdrawing effect causing the ketone in 8 to exist predominantly as the hydrate--thus mimicking the tetrahedral transition state during hydrolysis of the scissile Leu10--Val11 amide bond. PMID- 3111890 TI - On the role of N-7-mercaptoheptanoyl-O-phospho-L-threonine (component B) in the enzymatic reduction of methyl-coenzyme M to methane. AB - The reduction of methyl-coenzyme M (CH3SCoM) to methane in methanogenic bacteria is dependent on component B (N-7-mercaptoheptanoyl-O-phospho-L-threonine, HSHTP). We report here that S-methyl-component B (N-7-(methylthio)heptanoyl-O-phospho-L threonine, CH3SHTP) can substitute for neither CH3SCoM nor HSHTP in the methyl CoM reductase reaction. Rather, CH3SHTP proved to be an inhibitor competitive with HSHTP (apparent Ki = 6 microM) and noncompetitive with CH3SCoM. These results make it very unlikely that HSHTP functions as a methyl group carrier. A role for HSHTP as direct electron donor for CH3SCoM reduction to CH4 is proposed. PMID- 3111891 TI - Induction of first cycles in primary hypothalamic amenorrhea with pulsatile luteinizing hormone-releasing hormone: a mirror of female pubertal development. AB - During pubertal development in girls, the attainment of regular ovulatory menstrual cycles usually is preceded by cycles that are either anovulatory or show a defective luteal phase. It is not known whether these defective cycles are caused by inadequate luteinizing hormone-releasing hormone (LH-RH) secretion or by an inadequate response of the pituitary-ovarian axis to LH-RH stimulation. To shed new light on this matter, the authors analyzed endocrine data from 12 menstrual cycles induced by pulsatile LH-RH therapy in five women with primary amenorrhea of hypothalamic origin. Anovulatory cycles occurred with and without an increase in estrogen excretion and with and without a luteinizing hormone surge. In addition, ovulatory cycles with and without deficient corpus luteum function were observed. Most of these types of anovulatory and ovulatory menstrual cycles also have been described during normal puberty. Therefore, these observations suggest that, during normal pubertal development, maturation of the pituitary gonadotropes and of the ovary occurs, as well as the increased secretion of LH-RH from the hypothalamus, which the overall process depends upon. PMID- 3111892 TI - In vitro fertilization and embryo transfer in patients with one ovary. AB - The purpose of this investigation was to compare follicular response and pregnancy rates in patients with one and two ovaries who have undergone in vitro fertilization (IVF). No statistically significant difference was found in serum estradiol levels on the day of human chorionic gonadotropin administration, mean number of follicles (greater than 15 mm), mean total number of oocytes recovered, mean number of mature oocytes recovered, or number of pregnancies per transfer. The total number of oocytes recovered in the one- and two-ovary groups was 47 and 123, respectively. There was a significantly greater mean number of immature oocytes recovered (1.5 +/- .03 versus 0.5 +/- 0.2, P less than 0.01) and embryos transferred (2.7 +/- 0.3 versus 1.7 +/- 0.3, P less than .04) in patients with two ovaries. Though not statistically significant, a trend was noted in the two ovary group for a greater number of pregnancies per transfer (9:25 versus 2:14). The authors conclude that single-ovary patients may have a reduced outcome with IVF compared with patients with two ovaries. PMID- 3111893 TI - Utilization of luteinizing hormone-releasing hormone agonist in pulmonary leiomyomatosis. AB - A patient presenting a recurrent episode of pulmonary leiomyomatosis has been treated with the LH-RH agonist buserelin at a dosage of 200 micrograms tid SC for 7 days, then 500 micrograms SC daily for a total period of 6 months. Basal serum E2 was suppressed during treatment and varied between 62 and 180 pmol/ml (mean, 129.4 +/- 14.5). Pulmonary symptoms completely disappeared during treatment, but no objective regression of the pulmonary lesions was observed. Because of the uncertainty of response of benign metastasizing leiomyomas to castration and because of the reversibility of the medical treatment, LH-RH agonist may be preferred to surgical castration in this pathology. PMID- 3111894 TI - Changes in thyroid function tests and sex hormone binding globulin associated with treatment by gonadotropin. AB - Increasing levels of E2 in gonadotropin-treated women stimulated hepatic synthesis of SHBG and TBG, and consequently increases in T4 concentration. Nevertheless, unchanged FTI and TSH suggested that a euthyroid state was maintained. The temporal patterns for the rise in serum concentrations of TBG and SHBG during gonadotropin therapy suggest that the synthesis of these proteins by the liver has different sensitivities to E2. PMID- 3111895 TI - Isoelectrofocusing profiles of human urinary LH and FSH. PMID- 3111896 TI - [Characteristics of the development of a hypoxic state in bronchial asthma in children]. PMID- 3111897 TI - [Spontaneous fluctuations in the composition of alveolar air at rest and under loading]. PMID- 3111898 TI - [Suppression by dopamine of GH release induced by GRF in a case of acromegaly]. AB - Inhibition of plasma GH by dopaminergic agonists is one of the characteristics of the GH secretion in acromegaly. GRF is known to stimulate GH secretion in most patients with acromegaly. In order to elucidate the relationship between GRF and dopamine in regulating the secretion of GH in this disease, we examined plasma GH responses to dopamine (DA) infusion (4 micrograms/kg/min), GRF injection (100 micrograms i.v.), sulpiride (SP) injection (200 mg i.v.), a DA blocker, DA plus GRF and SP plus GRF in a 51-year-old male patient with acromegaly. Plasma GH was reduced to 14% of the initial level by iv infusion of DA, and was elevated to 158% by iv injection of GRF. No considerable change was observed in plasma GH by iv infusion of SP (114% of the initial level). GH release induced by GRF was remarkably reduced by simultaneous administration of DA (28% of the initial level), whereas SP administration did not affect GRF-induced GH release (154%). The marked reduction of GH release after DA plus GRF seems to suggest that the effect of DA on the GH regulation is stronger than that of GRF in this acromegalic patient. It is suggested also that endogenous DA may not play an inhibitory role in GH secretion in this case since DA blockade by SP did not raise basal GH levels and the GH response to GRF. PMID- 3111899 TI - [Ovulation induction with pulsatile gonadotropin-releasing hormone and continuous human menopausal gonadotropin in polycystic ovarian disease]. AB - Various treatments have been applied to polycystic ovarian (PCO) type of anovulation. However, none of them was definitive in terms of the efficacy and side effects. Six anovulatory women of PCO type were treated with pulsatile gonadotropin-releasing hormone (GnRH) of various pulse intervals and continuous human menopausal gonadotropin (hMG). The efficacy and rationale of the treatments were discussed. The subjects were diagnosed PCO by GnRH test and/or laparoscopy. They did not ovulate with clomiphene, clomiphene-hCG and hMG-hCG therapies. Their pretreatment serum FSH and LH levels and FSH/LH ratios were 6.9 +/- 1.2 mIU/ml, 15.7 +/- 5.1 mIU/ml, and 0.54 +/- 0.19 (Mean +/- SD), respectively. The treatment consisted of 3 protocols: 1) pulsatile GnRH (5-10 micrograms/pulse) of 90 min interval, 2) pulsatile GnRH (5-10 micrograms/pulse) of 120 min interval and 3) continuous hMG (150 IU/day) through subcutaneous route. Follicular growth was monitored sonographically and an intramuscular bolus of 10,000 IU hCG was given when the dominant follicle reached 20 mm in diameter. During both GnRH treatments serum FSH levels and FSH/LH ratios did not elevate substantially. Serum LH, E2 and PRL levels elevated acutely and transiently during the initial phase of GnRH treatments. Follicular growth was observed in a small fraction of the cases, but none of them ovulated. In contrast, continuous hMG treatment induced significant elevation in serum FSH levels (8.2 +/- 1.7 mIU/ml; p less than 0.01) and FSH/LH ratios (1.73 +/- 0.57; p less than 0.001). Transient hyperprolactinemia was accompanied with the preovulatory E2 rise. All the cases ovulated and 3 singleton pregnancies followed. These findings draw conclusions as follows. Pulsatile GnRH administration may desensitize the pituitary presumably due to increased GnRH pulse frequency as a consequence of two independent pulse generators, intrinsic and exogeneous. It may induce transient hyperprolactinemia through a paracrine system between gonadotrophs and lactotrophs. As a due course pulsatile GnRH therapy is questionable for ovulation induction in cases with functioning hypothalamic-pituitary axis. The fact that continuous hMG effectively induced follicle maturation with elevated FSH/LH ratios suggested that FSH dominance might be a prerequisite for folliculogenesis. The fluctuating nature of gonadotropins might not be mandatory for folliculogenesis. PMID- 3111900 TI - A reappraisal of the maternal syndrome associated with hydrops fetalis. AB - A pregnancy complicated by severe rhesus isoimmunization can not only lead to fetal loss but may also be complicated by a rarely described maternal syndrome. The unusual clinical features of one such case and the probable underlying pathophysiology are described. PMID- 3111902 TI - Comparison of two modified Sauton media for tuberculin production. PMID- 3111901 TI - Hormonal contraception: new long-acting methods. PMID- 3111903 TI - Production and purification of eta (ETA) precipitinogen, species-specific to mycobacterium tuberculosis and its intradermal reactivity. AB - The partially purified preparation of eta precipitinogen which is species specific for Mycobacterium tuberculosis showed skin reaction specificity for guinea pigs sensitized with M. tuberculosis. Strains of M. tuberculosis and the conditions for cultivation for optimal production of stable eta precipitinogen preparation in a large scale were investigated. Additional purification of procedures of the partially purified preparation of eta were also investigated. The significance of eta precipitinogen in the diagnosis of mycobacterial infection is discussed. PMID- 3111904 TI - Comparative study of biological potencies of different tuberculins. PMID- 3111905 TI - Comparative testing of the potency of different PPD preparations. AB - The potency of different PPD preparations, obtained from M. tuberculosis and M. bovis was investigated in the guinea-pig test. The groups of animals were immunized with dried mycobacterium powder (obtained from M. tuberculosis, M. bovis and M. tuberculosis + M. bovis), suspended in sterile liquid paraffin oil and with BCG vaccine. The potency tests were carried out according to the WHO requirements. Independently of the immunization method, a significantly greater potency of homologous versus heterologous PPD could not be demonstrated. The mixed PPD preparation (obtained from M. tuberculosis + M. bovis) was fractionated on SEPHAROSE 6 B and SEPHACRYL S 200 column. The potency of different fractions compared to the non-fractionated material was determined in the guinea-pig tests. The animals were immunized by dried mycobacterium powder (obtained from M. tuberculosis + M. bovis), suspended in sterile liquid paraffin oil. The IU content of fractions was calculated according to their protein N content, compared to the non-fractionated material. In these experimental conditions PPD fractions with significantly greater potency than the non-fractionated material could not be found. As a final conclusion we suggest that the desired improvement of tuberculosis diagnostics can be achieved not only by using PPDs derived from different mycobacteria but by further immunochemical purification of the tuberculin preparations and extensive testing of the purified materials in human beings as well. PMID- 3111906 TI - Sensitivity to avian sensitin of tuberculin reactors in Belgium. AB - It was proposed that a study should be made on the specificity of the reactions of 1068 subjects reacting "weakly to moderately" to an intradermal test with 2 units of PPD RT23; 43% were classified as "positives" (greater than or equal to 10 mm) and Palmer type IV indurations or merely erythema were seen in 81%. Three months later, the same people were retested, this time with 2 units of PPD RT23 and, simultaneously, with 0.1 mcg of avian sensitin: 23% of all reactors (13% of all "positives", but none with a Palmer type I of II induration) had completely lost their sensitivity to RT23. Of the 1068 original reactors, 87% reacted to avian sensitin and 69% did so with a reaction greater than or equal to to human RT23. According to the results of this double test, and depending on the strictness of the comparative criterion, 69% to 84% of the original reactors (65% to 78% of the "positives") would be classified as non-specifically infected. There was a high degree of agreement between an induration greater than or equal to 10 mm to PPD RT23 in the second test and classification as specific infection, based on a comparative criterion. PMID- 3111907 TI - The significance of a dual skin test with PPD and PPD-B in humans after BCG vaccination. AB - Dual skin tests with tuberculin purified protein derivative (PPD) and with one of the following antigens prepared from mycobacteria other than M. tuberculosis, such as PPD-Y, PPD-G, PPD-B, PPD-F, etc., are performed to establish the frequency of "atypical" mycobacterial infection in a given population. However, most of this work has been done in areas where BCG vaccination was rarely implemented, if at all. The purpose of this study was to assess the significance of a dual skin test using PPD and PPD-B in a population which had been vaccinated with BCG. It was found that in a population with a high level of sensitivity to PPD, median skin reaction 12 mm, only 7% of the subjects tested gave a greater response to PPD-B than to PPD, whereas in a population with a low level of sensitivity to PPD, median skin reactions 3 mm, 36% of the subjects gave a greater response to PPD-B than to PPD. It would appear, therefore, that in a population vaccinated with BCG and with a low level of sensitivity to PPD, a relatively high percentage of positive reactors, those with an induration of 5 mm or more to either PPD or PPD-B, gave a larger skin reaction to PPD-B than to PPD. To avoid erroneous conclusions as to whether or not there is a high frequency of atypical infection in a given population, the authors suggest that the BCG status of those tested with PPD and PPD-B be taken into consideration when interpreting the results of an epidemiological survey that includes an atypical antigen such as PPD-B. PMID- 3111908 TI - Response to tuberculin PPDs prepared from M. tuberculosis and other mycobacteria in a 1 to 16 year old population. PMID- 3111909 TI - Freeze-dried activated substrate for factor VIII assays. AB - Factor VIII-deficient plasma (natural or artificial) mixed with kaolin and phospholipid can be lyophilized to provide ready-to-use substrate which is stable for months at 4 degrees C and usable after many weeks at room temperature. Factor VIII assays are much simplified and more reproducible using this reagent and can be quantified with the aid of a programmable calculator according to the equation (formula; see text) as % of standard and X, S and B are clotting times of test, standard and blank samples respectively. The slope of the log/log function (k) is approximately--6.5. PMID- 3111910 TI - Interim results of surveillance for NANBH in patients receiving heated concentrates produced in England. AB - Coagulation factor concentrates prepared in England are all subjected to heating in solution or in the lyophilised state. Concentrates of factor VIII, factor IX (II and X), factor VII and factor XI are terminally heated in the lyophilised state at 80 degrees C for 72 h but the current fibrinogen concentrate withstands only 70 degrees C for 24 h. 33 patients receiving factor VIII concentrate (code 8Y) and factor IX concentrate (code 9A) for the first time have had regular liver function tests (LFTs) and we have at least some data on 26 of them exposed for greater than 3 months. Of these 26 patients, four had received no blood products before 8Y, 15 had received only cryoprecipitate before 8Y, and seven had received no blood products before 9A. Nine have missed only one or none of their two weekly tests, four have missed two or three tests and on the remaining 13, the LFT follow-up has been unsatisfactory, although in some cases clinical examination has been helpful. 12 batches of 8Y from greater than 70,000 donations and seven batches of 9A from greater than 40,000 donations have been used. In 13 patients who have had regular prospective LFTs, none has had an ALT or AST level above twice normal. One patient followed only irregularly has shown an isolated ALT rise at eight weeks, unconfirmed at nine or at 17 weeks. PMID- 3111911 TI - Inactivation of HTLV-III/LAV, hepatitis B and non-A/non-B viruses by pasteurization in human plasma protein preparations. AB - Pasteurization (heat treatment at +60 degrees C for 10 hours in solution) during the production of human plasma protein preparations has proved useful 1. to inactivate a broad spectrum of viruses and 2. in combination with stabilizers to leave the nativity of the products unaffected. Their efficacy has been experimentally tested for HTLV-III/LAV, Hepatitis B and non-A/non-B viruses. The following preparations were tested: with HTLV-III/LAV: Factor VIII, Factor IX, AT III, AHC and PPSB; with Hepatitis B virus: Factor VIII, Factor XIII, AT III, PPSB and Fibrinogen; with Hepatitis non-A/non-B virus: Factor VIII and AT III. PMID- 3111912 TI - Plasma fractionation in blood transfusion service. AB - Hungary's health service (10 million pop.) needs about 2000 kg of albumin, 10 million units of Factor VIII 1-1,5 million units of Factor IX, and 3 million micrograms of anti D IgG a year. The plasma for these products is collected from volunteer blood donors and by plasmapheresis. 90% of the albumin is produced by the Cohn method. To study the efficiency of a new chromatographic plasma fractionation method (3), we installed an integrated system for the production of factor VIII, PCC, albumin and intravenous IgG. About 10% of the total albumin is produced using this system. The paper discusses the results of 3 years of experimentation with the chromatographic system. The problems of the method are also analysed in detail. PCC is now in clinical use, the albumin is under clinical trial and the clinical trial of the i.v. IgG will start soon. PMID- 3111913 TI - Extended survival of MHC-compatible islet grafts from diabetes-resistant donors in spontaneously diabetic BB/W rat. AB - Transplantation of a large inoculum of incubated islets of MHC-compatible donors led to an extended survival of the grafts to an average of greater than 86 days in 71% of male diabetic BB/W recipients. Identical results were obtained whether the immunologically privileged abdominal testis or the nonimmunologically favored renal subcapsular space was used as the organ site for the injection of the islets. Survival of the islet grafts was also independent of the duration of diabetes in the BB/W rats at the time of transplantation. These results showed that under our experimental conditions the grafted islets were able to become established and survive for extended periods in nonimmunosuppressed spontaneously diabetic BB/W hosts. PMID- 3111915 TI - Gallbladder motor function in chagasic patients with megacolon and/or megaesophagus. AB - Gallbladder motor function was evaluated in 21 Chagasic patients with megacolon and/or megaesophagus and the results were compared with those obtained in 19 control subjects. Gallbladder contraction was evaluated by the radiologic method after the application of two different stimuli: an exogenous one consisting of intravenous injection of cholecystokinin octapeptide at the dose of 30 ng/kg over a period of 1 min, radiologic evaluation was performed before and 5, 10, 15 and 20 min after the stimulus; an endogenous one produced by standardised intraduodenal instillation of a lipid emulsion, radiologic evaluation was performed before and 3, 5, 10, 15, 20, 25 and 30 min after the beginning of intraduodenal infusion. The gallbladder of the Chagasic patients was found to be hypersensitive to both stimuli, since it contracted in a statistically more intense manner, with contraction starting earlier and lasting longer than among the controls. This difference in contracting behavior suggests impairment of the inhibitory intrinsic innervation of the gallbladder. PMID- 3111914 TI - Six-month treatment with sorbinil in asymptomatic diabetic neuropathy. Failure to improve abnormal nerve function. AB - The effect of long-term treatment with the aldose reductase inhibitor sorbinil (125 mg daily for 6 mo) was examined in 22 diabetic patients with subclinical abnormalities of nerve function. This was a placebo-controlled, double-blind crossover trial in which each of the two treatment periods lasted 6 mo. Peripheral nerve function was assessed electrophysiologically and by quantitative sensory testing; autonomic function was assessed by measurement of five cardiovascular reflexes and of mean heart rate from a 24-h ECG recording. Measurement of erythrocyte sorbitol concentrations demonstrated very significant inhibition of aldose reductase activity with sorbinil treatment, but no concomitant improvement in either peripheral or autonomic nerve function was observed. PMID- 3111916 TI - Prostaglandin protection against ethanol-induced gastric injury: regulatory effect on the mucus glycoprotein metabolism. AB - Effects of ethanol and prostaglandin on the metabolic processes of gastric mucosal cells have been evaluated by studying the biosynthesis and intra- and extracellular distribution of mucus glycoprotein. The rat gastric mucosal cell suspensions were subjected to a short-term tissue culture in the presence of 0 1.5 M ethanol and 0-100 ng/ml 16,16-dimethyl prostaglandin E2 (DMPGE2), using [3H]proline and [3H]palmitic acid as markers of mucin apoprotein synthesis and modification. Ethanol at concentrations of 0.02-0.1 M stimulated the glycoprotein synthesis, but the product was 2-3 times more extensively and rapidly degraded by pepsin than the glycoprotein synthesized in the absence of ethanol. Higher concentrations of ethanol (0.1-1.5 M) caused a marked reduction in the glycoprotein synthesis and a depletion of the intracellular mucus glycoprotein stores, and at 1.5 M ethanol the synthetic processes ceased to function. When the incubated tissue cultures were challenged with DMPGE2, the highest synthetic and secretory stimulation was achieved at 10 ng/ml. The peptic susceptibility of the glycoprotein synthesized in the prostaglandin-enriched culture was somewhat lower than that of controls, and the proportion of the undegraded glycoprotein remaining after 22 h of digestion was significantly higher. Furthermore, the intracellular compartments were not depleted of mucus glycoprotein and the amount of the mucin apoprotein precursor increased to about 30%. Addition of DMPGE2 prior to ethanol treatment resulted in the stabilization of cellular processes and the cells responded as if ethanol was not present in the medium. Moreover, the intracellular stores of mucus glycoprotein were not depleted and the secretory rate was moderately elevated. The regulatory effect of DMPGE2 on the glycoprotein synthesis and distribution was significant, but diminished with increasing amounts of ethanol in the medium. The results suggest that DMPGE2 imposes a stabilizing effect on the secretory processes and controls the mucus glycoprotein synthesis, but the extent of this protective action against ethanol is limited and depends upon the concentration of ethanol penetrating the mucosal cells. PMID- 3111917 TI - Use of calcium depletion and chlorpromazine to study calcium dependence of secretory detergent action in the colon. AB - The role of Ca2+ in the in situ secretory response of rat colon and pig ileum was studied by chelation depletion of Ca2+ and by treatment with chlorpromazine. The effect of depleting lumenal Ca2+ by chelation and the effect of intraperitoneal administration of chlorpromazine were determined relative to colonic permeability and net fluid flux measured across the rat colon or pig ileum. Replacement of Ca2+ in the perfusate by 1.0 mM ethyleneglycol-(bis-beta-ethylaminoether) (EGTA) did not produce significant changes in the net absorptive fluid flux measured in the control state or in the net secretory fluid flux caused by secretory detergent agents. The concentration of EGTA used in the perfusate did not alter mucosal permeability. Nonsecretory bile acids or A23187 had no effect on net colonic fluid flux or on colonic permeability to mannitol in the rat. The known correlation between net fluid flux and increased colonic permeability to polar molecules has been confirmed for the secretory detergent compounds. Chlorpromazine pretreatment caused a partial reversal of net secretory fluid fluxes induced by deoxycholate and high concentrations (6.0 mM) of ricinolate and dioctyl sulfosuccinate without significantly altering mucosal permeability to mannitol. We conclude that depletion of lumenal Ca2+ is not an effective method for determining the possible Ca2+ dependence of these intestinal secretory events. The antisecretory actions of chlorpromazine may provide some indirect evidence for Ca2+ involvement in the secretory effects of the detergent class of laxative compounds. Permeability may be essential for secretion caused by these agents, but the driving force would appear to be provided by the active transfer of electrolytes from the blood to the lumen of the colon. PMID- 3111918 TI - Changes in gastro-intestinal motility induced by cholera toxin and experimental osmotic diarrhoea in dogs: effects of treatment with an argillaceous compound. AB - Effects on digestive motility of two agents which induce diarrhoea were investigated in conscious dogs chronically fitted with strain-gauge transducers sutured to the serosa of the antrum, the jejunum and the proximal colon and with a catheter inserted into the duodenum. Effects were tested before, during and after treatment with an argillaceous compound, smectite, at a dose of 100 mg/kg/day for 6 days. Smectite treatment alone induced only minor changes in gastric motility with a decrease in the motility index and an increase in the duration of the post-prandial disruption of gastric migrating motor complexes (MMCs). Intraduodenal administration of cholera toxin (200 micrograms) before smectite treatment disrupted MMCs on the stomach and the jejunum for more than 10 h without affecting colonic motility. These effects were still seen when cholera toxin was administered on the 3rd day of smectite treatment but were partially antagonized on the 6th day of treatment. Intraduodenal infusion of a hypertonic mannitol solution (900 mosm/l, 6 ml/min for 1 h) transiently disrupted gastric and jejunal MMCs, stimulating colonic motility for more than 6 h and inducing abundant diarrhoea 45-60 min after the beginning of the infusion. When the mannitol infusion was repeated on the 3rd and 6th days of smectite, gastric and jejunal motor disturbances persisted while colonic hyperactivity was abolished and onset of diarrhoea was delayed by more than 8 h. We thus conclude that smectite treatment has an antidiarrhoeal effect, partially antagonizing digestive motor disturbances induced by two agents used to provoke experimental diarrhoea. PMID- 3111919 TI - Influence of the prostaglandin E1 analogue Rioprostil on the human gastric mucosa. AB - Ten healthy volunteers received the prostaglandin E1 analogue Rioprostil 300 micrograms b.i.d. for 1 week. Endoscopically obtained biopsies were investigated with tritiated thymidine and autoradiography to determine the rate of cell proliferation and with a texture-analyzing system to measure the intracellular amount of mucus in the epithelial cells. Rioprostil did not alter the tritiated thymidine labeling index in the antral area but did significantly depress it in the fundic area. The mucus content was unchanged in the antrum but was significantly increased in the fundus. These observations indicate that Rioprostil given orally causes an enhanced cell maturation in the fundic area as well as an increased intracellular mucus content. Rioprostil seems to have no influence on the human antral area. PMID- 3111920 TI - Kingston General reviews the use of CMGs as a management tool. PMID- 3111921 TI - The economic evaluation of health care technology. PMID- 3111922 TI - Mechanism of the hyperketonaemic effect of prolonged exercise in insulin-deprived type 1 (insulin-dependent) diabetic patients. AB - The effects of moderate exercise of 2-h duration on the concentration and turnover rate of total ketone bodies were assessed in 7 acutely insulin-deprived Type 1 (insulin-dependent) diabetic patients with an isotope tracer technique using a constant infusion of 14C-beta-hydroxybutyrate. These results were compared to those obtained in 13 normal control subjects in whom a similar range of hyperketonaemia (approximately 1-6 mmol/l) was induced by fasting. In all subjects, the concentration and the rate of production of ketone bodies followed a biphasic pattern with an initial fall lasting for about 20 min followed by a secondary rise. When integrated over the entire working period, the exercise induced changes in ketone turnover were markedly dependent on the initial ketone body concentrations in both groups: at low ketonaemia (approximately 1 mmol/l), exercise increased the rate of production and disposal of ketones. These effects were progressively attenuated as basal ketonaemia rose and were reversed to an inhibitory action in markedly ketotic subjects (greater than 4 mmol/l). Despite the finding that, at high ketosis, exercise inhibited ketogenesis to a similar degree in control subjects and diabetic patients, the changes in concentration recorded at the end of exercise were different in the 2 groups: ketonaemia was reduced in fasted control subjects and increased in the diabetic patients. These data suggest that, contrary to a widely accepted opinion, the hyperketonaemic effect of prolonged exercise in ketotic diabetic patients does not result from an exaggerated stimulation of ketogenesis, but from some defect in their removal capacities for ketones, possibly related to insulinopenia. PMID- 3111923 TI - Application of microencapsulation for toxicology studies. II. Toxicity of microencapsulated trichloroethylene in Fischer 344 rats. AB - Gelatin-sorbitol microcapsules containing 44.1% trichloroethylene (TCE) were prepared and mixed in NIH-07 rodent meal diet and provided at microcapsule concentrations of 0 (untreated control group), 1.25, 2.5, 5.0, or 10% (equivalent to 0, 0.55, 1.10, 2.21, or 4.41% TCE, respectively) to groups of 10 male F344 rats for 14 days. An additional control group received diets containing 5% empty capsules. For comparisons, TCE dissolved in corn oil was administered by gavage to different groups of 10 male rats for 14 consecutive days at dose levels adjusted to correspond to those in the feed study. Treatment-related deaths occurred only in the highest dose group of the gavage study. Body weight gain and feed consumption were reduced in high-dose groups of both the feed and gavage studies. There was no measurable loss of TCE in feed sampled from the cages during the study. Dose-related increases in organ (liver and kidney) weight/body weight ratios, individual cell necrosis in the liver, and hepatic microsomal NADPH cytochrome c reductase and peroxisomal palmitoyl-CoA oxidase and catalase activities were found in both the dosed-fed and gavage groups. Induction of cytochrome P-450 occurred only in the dosed-feed study. There were no significant compound-related pathologic lesions observed in the kidneys, the only other organ examined microscopically. Differences in lethality, cytochrome P-450 levels, and induction of microsomal or peroxisomal enzyme activities were attributed to differences in the method of dosing (gavage versus dosed-feed). The demonstration of no significant loss of TCE from the feed and of similar toxic effects produced by microencapsulated TCE via feed and TCE in corn oil via gavage indicate that microencapsulation can provide an excellent alternative exposure route for studying the oral toxicological properties of volatile chemicals, such as TCE, in rats. PMID- 3111924 TI - Ankle sprain: an analysis of hospital referral from family practice. AB - A prospective study of 97 consecutive patients with inversion ankle injuries who were referred by their family practitioner to an accident and emergency department was carried out. Clinical features and resultant diagnosis were compared with 403 consecutive patients who referred themselves direct to the accident unit during the study period. There was no significant difference in the incidence of serious injuries between the two referral groups. Multivariate analysis of the combined referral groups revealed that age over 60 years, inability to weight-bear and distal fibular tenderness were critical diagnostic parameters and this result has been reported elsewhere. Further analysis of these features in each referral sub-group showed that significantly more patients referred by their family doctor were in the important over 60 years age group but that the incidence of the other diagnostic parameters were similar in the two populations. Using the presence of any one of these criteria as an indication for hospital referral with a view to X-ray examination, 70% of the patients seen first by their own doctor did actually warrant radiography compared with 58% in the self-referred group. However, it is apparent that more efficient hospital referral from family practice is possible by use of the clinical parameters described above and no serious fracture would have been missed by a general practitioner using such a policy in this population. Analysis of the reasons for referral by general practitioners is discussed and a suggested management regime is provided for all patients with inversion ankle injuries who attend their own doctor in the first instance. PMID- 3111925 TI - [Nutritional approach to patients with burns]. PMID- 3111926 TI - [Significance of neopterin, gamma interferon and other immunologic parameters determined in a population of drug addicts, positive or negative for anti-HTLV III antibodies]. PMID- 3111927 TI - Opioid peptide biosynthesis: enzymatic selectivity and regulatory mechanisms. AB - Certain general principles determine the biosynthesis of most biologically active peptides, including the opioid peptides, from large protein precursors. In almost all instances, the active peptide is embedded in the precursor flanked on both sides by pairs of basic amino acids. The first step in processing involves a trypsinlike enzyme, cleaving to the carboxyl terminus of basic amino acids, and leaving the active peptide with a basic amino acid on the carboxyl terminus. A carboxy-peptidase peptidase B-like enzyme then removes the remaining basic amino acid. It has been unclear whether any endopeptidases with trypsinlike activity are selective for one or another basic amino acid. Recently a soluble endopeptidase has been identified that can cleave to both the carboxyl and amino termini of basic amino acids. Enkephalin convertase (carboxypeptidase E, H) (EC 3.4.17.10) has considerable selectivity, and appears to be physiologically associated with the biosynthesis of enkephalin as well as a limited number of other neuropeptides. The turnover of opioid peptides and other neuropeptides is most effectively ascertained by measuring levels of mRNA either biochemically or by in situ hybridization. Striking dynamic alterations include a pronounced increase in levels of proenkephalin mRNA in the corpus striatum after blockade of dopamine receptors, but changes in opioid peptide mRNA after opiate addiction are less clear. PMID- 3111928 TI - Inflammation and the mechanism of action of anti-inflammatory drugs. AB - Inflammation is caused by release of chemicals from tissues and migrating cells. Most strongly implicated are the prostaglandins (PGs), leukotrienes (LTs), histamine, bradykinin, and, more recently, platelet-activating factor (PAF) and interleukin-1. Evidence for their involvement comes from studies with competitive antagonists for their receptors and inhibitors of their synthesis. H1 histamine antagonists are effective for hay fever and some skin allergies such as urticaria, which indicates the importance of histamine in these conditions. Symptoms of rheumatoid arthritis are alleviated by the aspirinlike anti inflammatory drugs, which inhibit the cyclo-oxygenase enzyme and reduce synthesis of prostanoids. Corticosteroids prevent the formation of both PGs and LTs by causing the release of lipocortin, which by inhibition of phospholipase A2 reduces arachidonic acid release. They suppress the inflammation of rheumatoid arthritis and asthma. Currently, high doses of nonsedating H1 antihistamines and PAF antagonists are being tested for the treatment of allergic asthma. PMID- 3111929 TI - [Cortico-resistant and cortico-dependent forms of Crohn's disease]. PMID- 3111930 TI - [Exclusive elemental enteral diet in cortico-resistant and cortico-dependent forms of Crohn's disease]. AB - The aim of this study was to investigate the value of elemental diet in steroid resistant and steroid-dependent Crohn's disease. Elemental diet (Vivonex HN, 39.4 +/- 9.2 kcal/kg/d) was delivered through a nasogastric tube at a constant rate. Twenty therapeutic periods lasting from 20 to 74 days (median, 32 days) were undertaken in 18 patients. Elemental diet was well tolerated. Mean values of hemoglobin, serum albumin, and serum transferrin increased significantly through the therapeutic period; body weight and anthropometric data did not change significantly. The short-term response to elemental diet was excellent in 11 cases, demonstrated by achievement of clinical remission and steroid withdrawal; six patients had an incomplete remission and remained slightly active or had to be maintained under low dose steroids; three patients did not respond to therapy and had to be operated upon. During the follow-up (6-30 months), 8 patients out of 17 had a relapse. Relapse was controlled by medical therapy in 5 cases and led to surgery in the 3 other cases. We conclude that elemental diet, as total parenteral nutrition, is an effective therapy of steroid-resistant and steroid dependent Crohn's disease. However, elemental diet does not prevent relapse. PMID- 3111931 TI - [Effect of the PGE1 methyl analog misoprostol on the pregnant uterus in the first trimester]. AB - The effect of misoprostol, a PGE1 methyl analogue, on the pregnant human uterus was unknown at dosage levels normally used in the treatment of gastric and duodenal ulceration. Data from animal fertility and teratology studies suggested no activity at an anti-ulcer dosage level. In a double-blind placebo-controlled study, 300 patients (9.-12. week of gestation) were treated with two doses of misoprostol (study A: 2 X 400 micrograms; study B: 2 X 200 micrograms) or placebo during the evening before a legally permitted termination of first-trimester pregnancy. A partial or complete abortion occurred spontaneously in 11% of patients receiving misoprostol 2 X 400 micrograms, 9% of patients receiving misoprostol 2 X 200 micrograms and none of the patients receiving placebo. The incidence of vaginal bleedings (A: 45%, B: 34%), abdominal pain (A: 42%, B: 43%) and the softening of the cervix were all significantly increased by misoprostol treatment. These results show that the sensitivity of the human pregnant uterus to prostaglandin analogues cannot be reliably predicted from animal studies. Furthermore, misoprostol should not be used in human first-trimester pregnancy. The effect of misoprostol on second and third-trimester pregnancy (e.g. labour induction) is still unknown. PMID- 3111932 TI - [Histometric case report of a placenta following intra-uterine therapy of rhesus incompatibility]. AB - In Rh-incompatibility the human placenta shows a prominent retardation of maturation. The placental insufficiency caused by these changes, combined with the existing hemolysis, represents an additional danger to the fetus. In a patient with severe Rh-incompatibility several Rh-negative blood transfusions were performed between the 26th and 30th weeks of gestation via sonographically guided puncture of the umbilical vein. Morphometric studies of the placenta were performed and the results compared with data already obtained from normal mature placentas and placentas from pregnancies complicated by Rh-incompatibility. Small terminal villi with a surface area identical to normal mature placentas were found. There was no improvement in vascularization when compared with other placentas from Rh-incompatible pregnancies. Nevertheless, isolated rebuilding of epithelial plates was found. The authors interpret these morphological phenomena as a "partial postmaturation" of the placenta as regards the development of the terminal villi. The absence of reproliferation of the villous vessels as well as the lack of any extensive regeneration of the epithelial plates could be due to the short time which elapsed between transfusion therapy and the inevitable indication for caesarean section. Intensive intrauterine therapy reduces the risk to the fetus due to immunologic complications, as well that due to placental insufficiency, as evidenced by the additional differentiation of villi. PMID- 3111933 TI - [Experimental evaluation of the efficacy of tissue plasminogen activator]. PMID- 3111934 TI - Thyrotropin-releasing hormone (TRH): immunohistochemical distribution in tadpole and frog brain. AB - The anatomical localization of immunoreactive TRH (IR-TRH) was demonstrated by the peroxidase-antiperoxidase technique in the brain and pituitary gland of larval and adult Rana catesbeiana. In the adult frog main sites of IR-TRH are perikarya and neuronal fibers in the preoptic and infundibular nuclei of the hypothalamus and in the amygdala and diagonal band of Broca of the telencephalon. In addition, TRH-positive neuronal fibers and endings were found in the septum, pallium, and brain stem as well as in the preoptico-hypophyseal tract, the external zone of the median eminence (which matures during late larval stages), and the pars nervosa; fibers were less extensive in the pars intermedia, and were absent from the pars distalis. In early larval stages, the magnocellular nucleus of the posterior preoptic area is the main site of immunoreactive perikarya. During late stages the extensive adult pattern of distribution of IR-TRH becomes established. The study represents the first immunohistochemical demonstration of IR-TRH in larval anurans, and serves as a basis for clarification of the neuroendocrine regulation of metamorphosis. PMID- 3111935 TI - Isolation and characterization of a photorepair-deficient mutant in Drosophila melanogaster. AB - A mutation abolishing photorepair has been localized to map position 56.8 centimorgans on the second chromosome of Drosophila melanogaster. Strains homozygous for the phr allele are totally devoid of photorepair and partially deficient in excision repair. Both defects map to the chromosomal region between pr and c. Since a homozygous phr stock exhibits reduced photoreactivation, the corresponding wild-type allele plays a significant role in UV resistance. PMID- 3111936 TI - Reexamination of alcohol dehydrogenase structural mutants in Drosophila using protein blotting. AB - Using protein blotting and an immuno-overlay procedure, we have reexamined the cross-reacting material produced by ADH null-activity mutants generated with ethyl methanesulfonate (EMS). Of the 13 mutants, 11 have an immunodetectable polypeptide of wild-type size. The native and urea denatured isoelectric points (pI) establish that 7 of 13 of the mutations have no effect on protein charge. The electrophoretic mobilities of each variant on increasing percent acrylamide gels (Ferguson analysis), reveal that 9 of the 11 immunodetectable mutants have retained the ability to form dimers under native conditions. None of the inactive mutant proteins has the ability to form the "adduct-bound" isozyme. We have found no correlation between protein pI and in vivo stability. The observed frequencies of specific charge class alterations do not dispute the propensity of G:A transitions previously found for EMS mutagenesis. PMID- 3111937 TI - Partial correction of structural defects in alcohol dehydrogenase through interallelic complementation in Drosophila melanogaster. AB - Alcohol dehydrogenases (ADH) from the F1 progeny of all pairwise crosses between 12 null-activity mutants and crosses between these mutants and four active variants, ADHn5 ADHF, ADHD and ADHS, were analyzed for the presence of active or inactive heterodimers. Gels were stained for ADH enzyme activity, and protein blots of duplicate gels were probed with ADH-specific antibody to detect cross reacting material. Crosses between the three major electrophoretic variants. ADHF, ADHS and ADHD, all produced active heterodimers. Four mutant proteins (ADHn2, ADHn4, ADHn10 and ADHn13) did not form heterodimers with any other ADH subunit tested. Of the 28 crosses involving the remaining null activity mutants, 22 produce heterodimers. Twelve of these exhibit partial restoration of enzyme activity. In five cases of active heterodimers from null-activity crosses, Adhn11 supplied one of the subunits. In two crosses involving the active variant ADHD, the null activity mutant subunits (ADHn8 and ADHn3) destabilized the heterodimer sufficiently to cause inactivation of the ADHD subunit. In the cross between AdhF and Adhn3, the activity of the ADHF subunit was also greatly reduced in association with the ADHn3 subunit. Two crosses (Adhn1 X Adhn11 and Adhn5 X Adhn12) result in partial restoration of one of the homodimeric proteins (ADHn1 and ADHn12, respectively), as well as forming active heterodimers. PMID- 3111939 TI - Construction of a new plasmid vector that can express cloned cDNA in all translational reading frames. AB - Construction of a bacterial expression vector, pSI4001, is described. The vector contains the lac promoter-operator and three sets of ribosome-binding sites (RBSs) tandemly arranged in all possible reading frames. cDNA can be directly cloned downstream from these translational start points in the fixed and proper orientation by using the method of Okayama and Berg [Mol. Cell. Biol. 3 (1982) 280-289]. The open reading frame of any cDNA inserted may be automatically aligned in phase with either of the three ATG start codons, thus enabling its expression with a maximum theoretical probability of unity. Fusion with the lacZ gene (coding for beta-galactosidase) has shown that at least two of the three translation initiation sites exhibit high expression capacities and the remaining one can also function at a lower but significant rate. We used the vector to construct a bovine pituitary cDNA library, from which clones coding for prolactin were detected by immunological screening with an efficiency as high as two in three clones. The construction with triple RBSs should also provide a unique experimental model to study the regulation of overlapping translations. PMID- 3111938 TI - The effects of chromosomal rearrangements on the zeste-white interaction in Drosophila melanogaster. AB - Three gene systems have been shown to exhibit proximity-dependent phenotypes in Drosophila melanogaster: bithorax (BX-C), decapentaplegic (DPP-C) and white (w). In structurally homozygous genotypes, specific allelic combinations at these loci exhibit one phenotype, while in certain rearrangement heterozygotes the same allelic combinations exhibit dramatically different phenotypes. These observations have led to the suggestion that, through the process of somatic chromosome pairing, such loci are brought into sufficient proximity to permit effective passage of molecular information between homologues; rearrangement heterozygosity would then displace the homologues relative to one another such that this trans-communication is obviated. The genetic properties of the proximity-dependent allelic complementation (termed transvection effects) at the BX-C and DPP-C, are quite similar. Chromosomal rearrangements which disrupt transvection possess a breakpoint in a particular segment of the chromosome arm bearing the transvection-sensitive gene (arm 2L for the DDP-C and 3R for the BX C); this segment of each arm has been termed the critical region by Lewis (1954). As determined by cytogenetic analysis of transvection-disrupting rearrangements, the critical regions for the BX-C and DDP-C transvection effects extend proximally from these loci for several hundred polytene chromosome bands (Lewis 1954; Gelbart 1982). The interaction between the zeste and white loci appears to depend upon the proximity of the two w+ alleles. By use of insertional duplications, displacement of w+ homologues has been shown to interfere with the zeste-white interaction. In contrast to transvection at bithorax and decapentaplegic, however, only breakpoints in the immediate vicinity of the white locus can disrupt the zeste-white interaction (Gans 1953; Green 1967; Gelbart 1971; this report). In this report, we investigate the basis for the difference in the size of the BX-C and DPP-C critical regions from that of white. We test and eliminate the possibility that the difference is due to the presence near the white locus of a site which mediates somatic chromosome pairing. Rather, our evidence strongly suggests that the zeste-white interaction is, at the phenotypic level, much less sensitive to displacement of the homologous genes than is transvection at either the BX-C or DPP-C. We also show that many of the breakpoints in the vicinity of the white locus do not behave as if they are disrupting a critical region for somatic chromosome pairing. Given these results, we suggest that the zeste-white interaction and transvection are two different proximity-dependent phenomena. PMID- 3111940 TI - Expression of mouse::human immunoglobulin heavy-chain cDNA in lymphoid cells. AB - A chimeric mouse variable::human constant immunoglobulin heavy-chain gene was expressed in transfected mouse Sp2/0 cells. The chimeric immunoglobulin genes were integrated in tandem in the genome of stably transformed cells. These integrated gene copies were amplified by selection with a second drug marker. The gene amplification led to an increase in the expression of chimeric heavy-chain protein. The level of gene expression appears to be related to the site of integration; a few gene copies in one transfectant can yield as much heavy-chain protein as many copies in a second transfectant. In addition, we found that an adventitious oligo(C) sequence, introduced by our method of gene construction at a site located 8 nt residues downstream from a splice acceptor, can apparently direct splicing towards a cryptic splice acceptor downstream from the oligo(C). PMID- 3111942 TI - Effect of ebony and yellow mutants of Drosophila melanogaster on adult survival and alcohol dehydrogenase activity. AB - The survival of ebony, yellow, ebony-yellow double mutant and their wild type was studied on two types of media. All genotypes showed greater survival in the presence of 10% ethanol (E) than on the control agar medium (C), with wild type showing greatest and the double mutant ebony-yellow least response. This increase in survival on E was negatively dependent on that on C. The relationship between alcohol dehydrogenase (ADH) activity and survival appeared to be negative on E. On C it was either slightly positive for males or constant for females. The degree of survival increase standardized in relation to survival on C [(E-C)/C] was more dependent on the level of ADH activity for the males (r = -0.98; p greater than 0.05) than for the females (r = -0.38; NS). In the complex interaction between morphogenes, ADH activity and survival, morphogenes increased the ADH activity and decreased survival on E. PMID- 3111941 TI - A developmentally regulated gvpABC operon is involved in the formation of gas vesicles in the cyanobacterium Calothrix 7601. AB - In the filamentous cyanobacterium Calothrix PCC7601, gas-vesicle (GV) formation is restricted to specialized filaments, called hormogonia. The differentiation of these cells is controlled by environmental factors, such as light intensity and/or wavelength. The structural gene (gvpA) encoding a GV protein in this cyanobacterium has been previously cloned and sequenced. Two other genes, gvpB and gvpC have been found in the sequence downstream from gvpA. The gvpB gene corresponds to a second copy of gvpA, encoding an identical protein. Unlike the GV protein, the product of the gvpC gene is predominantly hydrophilic, as deduced from nucleotide sequence. Interestingly, the internal part of the gvpC gene is composed of four contiguous repeats, each containing 99 bp, forming highly homologous repeats in the deduced amino acid sequence. Another kind of periodicity has been detected inside the 99-bp repeats, suggesting that the gvpC gene might have evolved by amplification of a 33-bp-long primordial building block. The function of this gene remains to be elucidated. Finally, we have shown that the three genes, gvpA, gvpB, and gvpC, are organized in an operon that is exclusively expressed during GV formation in hormogonia. PMID- 3111943 TI - Age and protein malnutrition: effects on the febrile response. AB - Elderly hospitalized patients frequently do not mount a vigorous febrile response. This diminished response could be due to the combined effects of age and protein malnutrition, a common problem in the elderly. We studied the effect of mild protein deprivation on the febrile response to interleukin-1 (IL-1) and endotoxin in young, middle-aged, and elderly Fischer rats. In each age group, rats received either a standard (23% casein) or low protein (8% casein) diet for 5 weeks (young rats) or 8 weeks (middle-aged and elderly rats). Each rat received an intraperitoneal injection of IL-1, 10 micrograms/kg endotoxin, or 100 micrograms/kg endotoxin and temperatures were measured over 6 h by implanted biotelemetry devices. Protein deprivation decreased the febrile response to IL-1 in all age groups and to endotoxin only in the young and middle-aged rats. Increasing age along did not decrease the febrile response to either pyrogen. Increasing age and protein deprivation did not have an additive effect in decreasing the febrile response to IL-1 or endotoxin. PMID- 3111944 TI - Canthaxanthin retinopathy. An investigation by light and electron microscopy and physicochemical analysis. AB - The eyes of a patient with canthaxanthin retinopathy were obtained at autopsy and examined by light and electron microscopy. Various tissues of one eye were also studied by physicochemical methods. Morphologically, there were red, birefringent, lipid-soluble crystals in the inner layers of the entire retina. They were particularly large and numerous perifoveally, where they were also clinically visible, but they also occurred frequently in a ring-shaped form peripherally and, less frequently, equatorially. The crystals were located in a spongy degeneration of the inner neuropil, where atrophy of the inner parts of the Muller cells was noticed. The compound isolated from the retina was identical with synthetic canthaxanthin according to mass and proton-resonance spectroscopy. Quantitatively, the retina contained up to 42 micrograms canthaxanthin per gram of tissue besides a minor amount of other carotenoids. Of the other tissues of the eye, only the ciliary body contained measurable concentrations of canthaxanthin. From the great number and size of the crystals, on the one hand, and the relatively small amount of isolated canthaxanthin on the other, it was concluded that the crystals presumably represent a canthaxanthin-lipoprotein complex rather than pure canthaxanthin alone. Examination showed that clinically, only the central portion of the canthaxanthin thesaurismosis, where crystals are packed most densely, can be seen. PMID- 3111945 TI - Experimental carotenoid retinopathy. I. Functional and morphological alterations of the rabbit retina after 11 months dietary carotenoid application. AB - beta-Carotene, canthaxanthin, and beta-carotene plus canthaxanthin were administered to "chinchilla bastard" pigmented rabbits in their rabbit diet (approximately 200 ppm carotenoid per group). The effect of the carotenoids on retinal function and morphology was tested against a control group in the course of 11 months. Electroretinography showed that in contrast to the control animals, beta-carotene-treated rabbits produced increasing peak latencies of the scotopic b-waves. In the canthaxanthin-treated rabbits, a- and b-waves showed hypernormal amplitudes at low cumulative dosages (approximately 0.5-2 g) and reduced amplitudes at higher dosages (about 5 g). The peak latencies of the scotopic a- and b-waves increased remarkably. This effect was still stronger in the carotenoid combination. Histology and electron microscopy indicated that in contrast to the control animals, canthaxanthin-treated rabbits showed a reduction in retinal thickness in some samples. In particular, they exhibited alterations in the granular layers and a marked diminuation of the photoreceptor outer segments and morphological alterations of the photoreceptor inner segments with massive deposition of electron-dense material. In all animals treated with carotenoids, lipid droplets of the retinal pigment epithelium were enlarged in size and number. PMID- 3111946 TI - Behavioral effects of deprenyl in aged rats. AB - The effects of an inhibitor of MAO-B, deprenyl, have been studied in aged male rats. Subcutaneous (s.c.) injection of deprenyl was followed by a facilitated acquisition of active avoidance behavior and a facilitated retention of passive avoidance response in a dose-dependent manner. Ambulation and rearing of aged rats in an open field were increased by deprenyl. No effect was found on grooming behavior. Apomorphine-induced stereotypies were potentiated and haloperidol induced catalepsy was inhibited by deprenyl. Some elements of sexual behavior, i.e. latency to mounting and intromission and frequency of mounts and intromissions, were improved by deprenyl. Furthermore, deprenyl reduced the immobility of aged rats in a "despair" test, suggesting an antidepressant activity. Deprenyl seems to be effective in correcting some of the behavioral deficits of aged animals. Its behavioral effects can be related to the inhibition of cerebral MAO-B. PMID- 3111947 TI - Neuroendocrine evaluation in catamenial epilepsy. AB - The hypothesis that catamenial epilepsy depends on abnormal rhythmic hormone activity in the hypothalamus-pituitary-gonadal axis has never been critically tested. No significant modifications in the secretory pattern of pituitary hormones, both basally and in response to stimulatory tests, were found in a group of catamenial epileptic women. On the contrary, our data showed a reduction of luteal phase progesterone secretion. These findings indicate that an imbalanced secretion of ovarian steroids plays a role in the catamenial exacerbation of epilepsy. PMID- 3111948 TI - Partial seizures and migraine. AB - Epilepsy and migraine, despite some common features, have quite different pathophysiological mechanisms. Studies carried out on large population samples have shown that the relationships between migraine and epilepsy may be of the following type: associated attacks, with migraine and seizures occurring quite independently of one another; combined attacks, with the two types of attacks succeeding one another in time; basilar artery migraine with seizures and marked EEG abnormalities; benign epilepsies with occipital discharges, migraine and intercalated seizures. We report four cases of particular interest. PMID- 3111949 TI - Electroencephalographic alterations in migraine as an expression of "self deafferentation": a hypothesis. AB - The deafferentation of a leg in animal is followed by: local analgesia; generation in spinal cord and brainstem (along the sensitive fibers of second order) of quasi epileptic foci emitting continuously and/or in bursts, epileptic like discharges; scratching, attacks and finally autocannibalism of the deafferentated arm. This perverted behavior (autotomy) is attributed to an emission from the quasi epileptic foci of pain signals projected to deafferentated regions by cognitive sites of consciousness. The quasi epileptic foci, generating bursts of "automatic" pain, are considered the basic mechanism of pain in deafferentated and amputated humans. The nature of pain in migraine is assumed here as an analog to the mechanism of organic deafferentation; a generation in the brainstem of nociceptive foci, with the head as main projection. The enigmatic epileptic-epileptoid characteristics of EEG in migraineurs could be an expression of the electrically hyperactive "quasi epileptic foci" located mainly within the brainstem and generated by the insufficient opioid inhibition of sP-ergic neurons. PMID- 3111950 TI - May focal epileptic seizures be considered a marker of TIAs? AB - Late-onset focal epileptic seizures occurred in 8 patients with ischemic cerebro vascular disease (ICVD) and were associated with TIAs in 6 of them. History, physical, laboratory, ancillary examinations and follow-up revealed no other disease which might be responsible for the seizures. Moreover, time of onset and appropriate signs of ICVD suggested that transient cerebral ischemia was the most likely cause of seizures. PMID- 3111951 TI - Malignant migraine: the syndrome of prolonged classical migraine, epilepsia partialis continua, and repeated strokes; a clinically characteristic disorder probably due to mitochondrial encephalopathy. AB - We present ten patients with classical or common migraine of increasing severity accompanied by seizures of multiple patterns and increasing severity leading to episodes of epilepsia partialis continua. Long lasting deficits associated with hypodense lesions on CT and abnormal signals on MRI, then developed. Cortical blindness, cortical deafness and dementia were common. Five of the patients died in 1-10 years. Some of these patients had markers of mitochondrial disease (ragged red fibers and serum lactate elevation) and others with the same clinical picture did not. This group of patients indicates that mitochondrial encephalopathy may exist without evidence of myopathy, that the clinical syndrome is characteristic and that it should suggest the diagnosis even in the absence of muscular abnormalities. PMID- 3111952 TI - Anticonvulsant effects of calcium channel blockers in partial and generalized model epilepsies. AB - The calcium channel blockers D890 and verapamil reduced neuronal calcium currents in single snail neurons with intra- and extracellular applications, respectively. Epileptic discharges of single neurons in the rat's motor cortex (in vivo) were depressed in amplitude by intracellular injection of D890. Focal seizure discharges and generalized tonic-clonic seizure activity in the cerebral cortex of the rat were reduced by intracerebroventricular perfusion of verapamil. In non epileptic rats verapamil failed to exert a depressive effect on somatosensory evoked potentials and on the waves of the spontaneous EEG. PMID- 3111953 TI - Clinical evaluation of antithrombin III concentrate (BI 6.013) for disseminated intravascular coagulation in obstetrics. Well-controlled multicenter trial. AB - Antithrombin III (AT III) is known to be the most important inhibitor of serine protease in the coagulation system. In the presence of heparin, AT III is converted from its progressive activity state to an immediate activity state. In disseminated intravascular coagulation (DIC) in the field of obstetrics, the treatment has to be initiated very early. Heparin treatment, on the other hand, is critical since frequently postpartal or postoperative wound bleeding is present. We, therefore, established diagnostic criteria for the early diagnosis of DIC and investigated the clinical efficacy of a therapy with AT III in a well controlled comparative study versus the injectable synthetic protease inhibitor FOY. The results of the trial showed that the AT III group (92%; n = 24) was significantly (p less than 0.001) superior in clinical efficacy to the FOY group (60%; n = 15). No side effects whatsoever were observed after treatment with AT III concentrate (Behring Institute). From these results, it could be concluded that a single therapy with AT III concentrate can sufficiently control the symptoms of DIC in the field of obstetrics without the risk of increased bleeding. PMID- 3111954 TI - Increase of nonplasmin fibrinolytic activity in the lung and spleen of streptozotocin-induced diabetic rats. AB - In streptozotocin-induced diabetes in rats, nonplasmin fibrinolytic activity was found to be significantly increased in the lung and spleen, but not in the liver and kidney. The plasminogen-activator activities, either soluble or insoluble, were almost simultaneously increased in the lung, suggesting the possible release of plasminogen-activator from the lung to the blood. It seems likely that plasminogen-activator of the usual type and nonplasmin protease are also involved in thrombotic disorders in the experimental diabetes. PMID- 3111955 TI - [Natural inhibitors of the growth of Legionellae]. PMID- 3111956 TI - [Transient hydrocephalus during mumps meningo-encephalitis]. PMID- 3111957 TI - [Studies on the behavioral development of rats treated neonatally with l thyroxine]. AB - The effect of l-thyroxine administration from 2 to 10 days of age (Neo-T4) on the behavioral development was studied. Serum T4 levels in Neo-T4 rats showed a marked and dose-related decrease at 15 days of age and a less marked decrease at 62 days of age. The locomotor activity of the Neo-T4 rats was higher at 13 approximately 19 days of age and tended to be lower at 62 days of age than in the controls. At 17 days of age, apomorphine (0.1 mg/kg, s.c.) induced a marked increase in the frequency of sniffing down in the control males, whereas a decrease was noted in the Neo-T4 males. Age-matched females in both groups responded to apomorphine with a slight decrease in sniffing down behavior. An increase in the frequency of sniffing down by apomorphine (0.5 mg/kg) in adult Neo-T4 rats was less marked. TRH administration failed to induce hyperthermia in adult Neo-T4 males. The results indicate that neonatal administration of T4 in the rat induces alterations in the functional development of the brain in varying degrees dependent upon the functional integration of the neurons. An involvement of sex hormones is suggested. PMID- 3111958 TI - Plasma testosterone concentrations during postnatal development in the male common marmoset. AB - Repeated measurements of plasma testosterone (T) were made in 56 male marmosets from the day of birth until 300 days of age and in 44 adults (greater than 3 years). The resulting profile of plasma T during postnatal development shows higher levels during infancy (1-90 days) followed by a nadir between 100 and 170 days and then a progressive rise in T during puberty. Although T levels of up to 21 ng/ml were measured in infant males, mean levels (+/- SEM) were 5.4 +/- 0.6 ng/ml (days 1-10), declining gradually to 1.7 +/- 0.1 ng/ml (days 100-110). No increase in mean T levels between 15 and 100 days was identified, and the onset of puberty was earlier in some males than measured previously in this species. PMID- 3111959 TI - In vitro formation of a triazene compound by reaction of sulphadimidine and nitrite. AB - The interaction between the veterinary drug sodium sulphadimidine and nitrite has been studied under acid conditions and the formation of 1,3-di-(4-[N-(4,6 dimethyl-2-pyrimidinyl)sulphamoylphenyl)triazene (DDPSPT) was demonstrated. This compound was not mutagenic when tested on Salmonella typhimurium and Drosophila melanogaster. In addition to the formation of DDPSPT, desaminosulphadimidine was identified as a minor reaction product. PMID- 3111960 TI - [Cutaneous metabolism of arachidonic acid. Arachidonic acid metabolites in the pathophysiology of inflammatory dermatoses]. PMID- 3111961 TI - [Transdermal therapy of stable angina pectoris. Comparison of 2 different transdermal systems]. PMID- 3111962 TI - [Heat-stable hemolysin of Pseudomonas aeruginosa]. AB - Pseudomonas aeruginosa produces at least two distinct hemolysins: heat-labile hemolysin, which is known as phospholipase C, and heat-stable hemolysin, which is considered to be a glycolipid but its true nature is not found yet. Cellophane agar plate method was applied to hasten and enhance the hemolysin production by Pseudomonas aeruginosa, and the hemolysin obtained by this method was examined biochemically. This heat-stable hemolysin consisted of two major acidic glycolipids. One was considered to be the same glycolipid as that obtained by the same method of Jarvis and Johnson's from the peptone-glycerol culture filtrate of the same organism, which is composed of two moles of rhamnose and two moles of beta-hydroxy decanoic acid, and the other one being a glycolipid composed of one mole of rhamnose and two moles of beta-hydroxy decanoic acid. By this method, the rhamnolipid with one mole of rhamnose was produced more than the rhamnolipid with two moles of rhamnose, and they were produced in the same ratio from the first to fifth culture day. From the examinations of hemolytic activities of the hydrolyzed products of these glycolipids, the hemolysis producing moiety of the hemolysin was considered to be the dimer of beta-hydroxy decanoic acid contained in the glycolipid molecule. Hemolytic activities of these glycolipids are regarded as their detergent like effects. Since these activities are interfered by small amount of serum protein, their pathogenic role would not be important in vitro. However, their interaction with other toxic substances produced by this organism would be subject to be solved. PMID- 3111963 TI - [The effect of lithium treatment on the activity of central dopaminergic neurons]. AB - In the terminal regions of various dopaminergic neurons (i.e., median eminence, neurointermediate lobe, striatum, accumbens, prefrontal cortex, hippocampus, and amygdala, respectively), maintenance of rats on a diet containing lithium carbonate (0.23%) for 3, 7 or 21 days resulted in a significant increase in the accumulation of dihydroxyphenylalanine (DOPA) after the inhibition of the activity of aromatic l-amino acid decarboxylase with 3-hydroxybenzylhydrazine (NSD 1015, 100 mg/kg). There was also a significant increase in the concentrations of dopamine metabolites; dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT), in these brain regions of animals given lithium for 21 days when compared to control animals, suggesting a possible enhancement in dopamine synthesis and release. Furthermore, there was a significant increase in dopamine concentrations in anterior pituitary glands, but no significant change in other brain regions of lithium-treated animals. The inclusion of lithium in the diet resulted in a significant reduction of prolactin concentrations in serum and anterior pituitary glands. There was also a significant decrease in the secretion of prolactin from anterior pituitary tissues in vitro of lithium-treated rats. Chronic lithium consumption led to a significant decrease in beta-adrenergic receptor binding in selected regions of the rat brain, with no changes noted in alpha 2-adrenergic, dopaminergic D1 or D2 receptor binding. These results are suggestive that lithium treatment enhances the activity of various dopaminergic neurons. An increased release of dopamine from tuberoinfundibular dopaminergic neuron may account for the lithium-induced reduction of prolactin concentrations in serum and anterior pituitary glands, and the suppressed secretion of prolactin in vitro from anterior pituitary tissue. PMID- 3111964 TI - Immunohistochemical distribution of renal prostaglandin endoperoxide synthase and prostacyclin synthase: diminished endoperoxide synthase in the hepatorenal syndrome. AB - To evaluate possible causes of the diminished prostaglandin production in advanced hepatorenal syndrome, prostaglandin endoperoxide synthase and prostacyclin synthase were localized and semiquantitated by immunofluorescence in postmortem, biopsy and nephrectomy renal tissues. In normal kidneys, antiprostacyclin synthase serum caused intense staining in peritubular capillaries, in the adjacent renal interstitial cells and in glomerular mesangial regions. Antiprostaglandin endoperoxide synthase serum caused staining of collecting duct epithelial cells, cells of the thin ascending limb and possibly glomerular mesangial cells. Prostacyclin synthase-positive staining was graded 5+ (scale of 0+ to 5+) in all kidney samples. Medullary collecting tubule prostaglandin endoperoxide synthase-positive staining was graded 4+ or 5+ in kidney samples from patients with acute tubular necrosis or acute tubulointerstitial nephritis and from patients with liver failure without the hepatorenal syndrome. However, prostaglandin endoperoxide synthase-positive staining was markedly diminished or absent (average 1+) in patients with the hepatorenal syndrome. These data suggest that loss of the medullary prostaglandin endoperoxide synthase is the cause of diminished urinary prostaglandin E2 excretion in the hepatorenal syndrome. PMID- 3111965 TI - The synthesis of proteoglycans in fat-storing cells of rat liver. AB - Fat-storing cells (perisinusoidal stellate cells) were isolated by enzymatic digestion of rat liver and purified by a single-step Nycodenz gradient to yield 11.4 X 10(6) cells per liver, with a purity of 74% and a viability of 76%. Monolayer cultures of fat-storing cells incorporated both [35S]sulfate and [3H]glucosamine into glycosaminoglycans; the rate of incorporation increased with culture time (3-fold between the third and eighth days in culture). About 80% of newly formed glycosaminoglycans were secreted into the medium. Analysis of the types of glycosaminoglycans revealed a different pattern for cells and medium, respectively, which is subject to culture time. Heparan sulfate remains primarily cell-bound and, therefore, has a low fractional secretion rate. Chondroitin sulfate and even more dermatan sulfate are the main types of glycosaminoglycans in the medium. Dermatan sulfate represents about 60% of total medium glycosaminoglycans. In advanced cultures (eighth day), this type becomes the predominant one in the cell layer. The reduction of the molecular weight of native medium-sulfated molecules by papain digestion and beta-elimination and the puromycin-induced inhibition of their synthesis by more than 75% suggest the formation of glycosaminoglycans as complex proteoglycans. It is concluded that fat-storing cells are a major cellular source of dermatan sulfate and chondroitin sulfate in liver connective tissue. Since the pattern of proteoglycans of fat storing cells closely resembles that found in the fibrotic liver matrix, this cell type might be of pathogenetic significance for the accumulation of chondroitin sulfate and dermatan sulfate in cirrhotic connective tissue. PMID- 3111966 TI - Identification and characterization of liver nonparenchymal cells by flow cytometry. AB - Our objective was to correlate biochemical or functional properties that could be measured by fluorescence to individual nonparenchymal cell types by the simultaneous detection of forward angle light scatter and fluorescence. Cells were released from liver following selective digestion of hepatocytes by Pronase perfusion. To fractionate the cells according to size, isolates were subjected to unit gravity sedimentation on a 1 to 5% sucrose gradient. Flow cytometry was used to analyze the resulting fractions as well as the original unfractionated cells. This reaffirmed that forward angle light scatter is linearly related to the sedimentation velocity (size) of the cells and that it can be used to assess cell sizes in an unfractionated population. Endocytosis of fluorescently tagged particulates was studied by injecting either fluorescein isothiocyanate-tagged colloidal albumin or Coumarin-tagged latex beads (0.57 micron diameter) prior to Pronase perfusion. Beads were found only in the largest cells (Kupffer cells). Since endothelial cells could endocytose only colloidal albumin, they were readily differentiated from nonendocytosing, nonsinusoidal cells ("lymphocytes"). Staining cell protein with fluorescein isothiocyanate made possible the determination of relative protein content per cell ("lymphocyte": endothelial:Kupffer cell was 0.57:1.0:2.0). To determine relative esterase activities, mixed cell isolates were incubated in fluorescein diacetate ("lymphocyte":endothelial:Kupffer cells was 0.13:1.0:2.4). Uptake of rhodamine 123 was used to assess mitochondrial function ("lymphocyte":endothelial:Kupffer cells was 0.45:1.0:14.6). Mitochondrial volume per cell is known to be 1:2 for endothelial:Kupffer cells. Therefore, the large difference in rhodamine uptake is not related to volume. PMID- 3111967 TI - A multicenter, prospective study of posttransfusion hepatitis in Milan. AB - We studied the risk of posttransfusion hepatitis in recipients of blood collected from volunteer donors who tested negative for HBsAg and had serum ALT levels less than 1.5 times the upper limit of the normal range. Between October, 1983 and September, 1984, 676 consecutive patients who needed blood or plasma transfusions during or after elective surgery, who had no history of liver disease and had never received blood previously, were studied. The patients were given a total of 4,813 (mean = 7) units. Ninety-six patients developed posttransfusion hepatitis, which yielded a hepatic incidence of 20 cases per 1,000 units of transfused blood. Ninety-two patients had non-A, non-B hepatitis, 3 had hepatitis B and 1 had cytomegalovirus infection. The incubation periods for non-A, non-B hepatitis ranged from 2 to 26 (mean = 9.5 +/- 4) weeks. In 68 (73%) patients, the hepatitis was completely asymptomatic; only 24 (27%) patients developed symptoms, including jaundice and hepatomegaly. There were no cases of fulminant hepatitis. Sixty per cent of the patients still had elevated serum ALT levels 1 year after the onset of hepatitis. The 96 patients with hepatitis had received a mean of 9.6 blood units, as compared to a mean of 6.7 units for the unaffected patients (p less than 0.001). This study demonstrated that non-A, non-B hepatitis remains a common and important complication of blood transfusion despite screening of blood donors for HBsAg and elevated serum ALT levels. PMID- 3111968 TI - Leukotrienes as mediators in frog virus 3-induced hepatitis in rats. AB - The role of leukotrienes was investigated in frog virus 3-induced hepatitis in rats. Frog virus 3 elicited an enhanced generation of cysteinyl leukotrienes in vivo as monitored by measurement of N-acetyl-leukotriene E4 as the major endogenous metabolite of cysteinyl leukotrienes secreted into rat bile. N-Acetyl leukotriene E4 concentrations were elevated for more than 4 hr after frog virus 3 injection. In vitro experiments using cultured rat liver Kupffer cells of high purity indicated that these cells can produce and metabolize leukotrienes and are thus a possible source of leukotrienes elicited in vivo by frog virus 3. The selective 5-lipoxygenase inhibitor AA 861 and the dual inhibitor of arachidonate lipoxygenase and cyclooxygenase, BW 755C, reduced the hepatocellular injury after a high dose of frog virus 3 by about 50 and 80%, respectively, as judged from plasma activities of ALT and sorbitol dehydrogenase at 24 hr after frog virus 3 administration. Our in vivo and in vitro studies argue in favor of an important role of leukotrienes as mediators in frog virus 3 hepatitis in rats. PMID- 3111970 TI - Psychiatric expertise in clinical decision making for psychiatric inpatients. AB - Hospital boards and medical staffs are faced with difficult decisions about whether nonphysician mental health professionals should be given admitting privileges to psychiatric hospitals or treatment units. The authors describe the special medical expertise of the psychiatrist and define 11 indicators, such as a patient's need for new psychotropic medication or the presence of symptoms requiring medical or laboratory procedures, that can be used to determine whether psychiatric expertise is needed. The indicators were applied to a group of ten patients who constituted all admissions to a treatment unit in a private, nonprofit psychiatric hospital in a one-month period. At least half of the indicators were relevant to all the patients studied, suggesting the need for management by a psychiatrist. PMID- 3111969 TI - Addition of nitroglycerin to vasopressin therapy for the treatment of bleeding esophageal varices. PMID- 3111972 TI - A review of issues surrounding length of psychiatric hospitalization. AB - Recent emphasis on cutting the costs of psychiatric care and the possibility that reimbursement for psychiatric services will one day be based on diagnosis-related groups has stimulated debate about the proper length of psychiatric hospitalization. The authors review the literature on length of stay, focusing primarily on studies of the relationship between various patient and environmental variables and length of stay and studies comparing the outcomes of long and short hospitalizations. They conclude that diagnosis alone is not an accurate predictor of length of stay but may have predictive ability when combined with other data. Most studies found no differences in the outcomes of short and long hospitalizations. The authors identify numerous avenues for further research and are optimistic that a policy governing length of stay is within reach. PMID- 3111971 TI - Medical-psychiatry units: an economic alternative for consultation-liaison psychiatry? PMID- 3111973 TI - Rehabilitation outcome of long-term hospital patients left behind by deinstitutionalization. AB - In 1979 a Massachusetts state hospital initiated a plan to transfer 54 long-term residents of two wards to the community through a series of increasingly independent working and living arrangements. This study assesses the patients' residential and vocational status and living skills over a five-year period beginning in February 1979. The patients demonstrated a significant increase in living independence, but only eight were able to live continuously in the community after their discharge, and 24 never left the hospital. Overall, vocational status did not improve, and living skills improved only slightly. Living skills and vocational status were predictive of living independence. The authors identify several steps that the mental health field should take to promote success among chronic patients, deinstitutionalized or not. PMID- 3111974 TI - Variation in the expression of aphidicolin-induced fragile sites in human lymphocyte cultures. AB - A correlation between specific fragile sites and cancer breakpoints has been suggested raising the question of fragile site expression as a predisposing factor in the occurrence of cancer in some persons. Before addressing the question of increased fragility among patients at high risk for cancer, we analyzed the variability of aphidicolin-induced fragile sites among nine normal persons and also among repeated samples from three of these individuals. Considerable variation in both the frequency and location of these fragile sites was observed and the data strongly suggest the significant variation of 6 of the 16 selected sites to be primarily due to sampling differences. These findings indicate that the use of fragile sites as a screening tool for patients at high risk of cancer should be carefully monitored relative to the variation inherent in both culture and individual expression. PMID- 3111975 TI - The gene coding for the human T-lymphocyte CD2 antigen is located on chromosome 1p. AB - A cDNA clone encoding the human T lymphocyte sheep erythrocyte receptor [the CD2 (T11) antigen] was used as a probe to define the chromosomal location of the gene. The signal, revealed by hybridisation to Southern blots of genomic DNA from somatic cell hybrids, showed a high degree of concordance for human chromosome 1. In particular, the hybrid F4Sc13C19 which contained the short arm only of human chromosome 1 was positive. The location of the CD2 gene to 1p13 was confirmed by in situ hybridisation. PMID- 3111976 TI - Neisseria gonorrhoeae: subdivision of auxogroups by genetic transformation. AB - Genetic transformation was used in an attempt to subdivide the most prevalent auxotypes of Neisseria gonorrhoeae in local isolates. The large proline requiring (Pro-) group could be divided into two genetic types, as could the less common arginine requiring (Arg-) group. The large arginine, hypoxanthine, and uracil requiring (Arg- Hyp- Ura-) group could not be subdivided by this method. The genetic relation between these and other auxotypes was investigated. PMID- 3111977 TI - Serovars, auxotypes, and plasmid contents of PPNG strains from outbreak in Amsterdam. AB - The first outbreak of penicillinase producing strains of Neisseria gonorrhoeae (PPNG) in Amsterdam in 1981-2 was caused mainly by African strains carrying the 24 megadalton transfer plasmid (Afr+) that were non-requiring (NR) and inhibited by phenylalanine (pheni), but African strains without the transfer plasmid (Afr-) that were NRpheni and Afr+ NR strains were also found. Serological classification, using two monoclonal antibody systems, showed that three main serovars (Ae/Av, Aedih/Arst, and Bacejk/Brpyust) could be distinguished in these PPNG strains, which indicated exchanges of plasmids in these serovars. The serovar Ae/Av predominated in the Afr+ and Bacejk/Brpyust in the Afr- strains. PMID- 3111978 TI - Serological ecology of Neisseria gonorrhoeae (PPNG and non-PPNG) strains: Canadian perspective. AB - One hundred and thirty eight penicillinase producing Neisseria gonorrhoeae (PPNG) and 239 non-PPNG strains were characterised serologically using a panel of seven monoclonal antibodies directed against protein 1A and seven against protein 1B. An association between serovar and susceptibility to antimicrobial agents, auxotype, and plasmid content was observed. Serogroup WI strains were more sensitive to penicillin, ampicillin, tetracycline, erythromycin, cefoxitin, and cefuroxime. Sixty five (82%) of the 79 WI strains were typed as being serovar Aedgkih, and 47 (72%) of these strains required arginine, uracil, and hypoxanthine for growth (AUH-). Seventy one (44%) of 160 WII/WIII strains were serovar Bacejk, and 42 (59%) of these required proline, citrulline, and uracil for growth (PCU-) and were plasmid free. Serovars Bcgk, Beghjk, Bacjk, and Bajk were associated with resistance to antimicrobial agents. Analysis of PPNG isolates showed a new serovar, Af, which was associated with strains imported from Malaysia and Singapore that required proline and ornithine for growth (Pro Orn-) and carried the 24.5 megadalton transfer plasmid, the 2.6 megadalton cryptic plasmid, and the 4.5 megadalton penicillinase producing plasmid. Other associations between serovar and geographical location were noted. PMID- 3111979 TI - New microbial and host factors in disseminated gonococcal infection: case report. AB - Disseminated gonococcal infection was diagnosed in an immunocompromised patient who presented with oliogoarthropathy and tenosynovitis. The gonococcal isolate was prototrophic, showed intermediate resistance to penicillin, and belonged to serogroup WII/III. An isolate from the patient's sexual contact showed similar characteristics. The patient had a Saccharomyces opsonin defect, which is associated with childhood infections and has not been reported previously in association with disseminated gonococcal infection. The pathogenetic importance of the unusual isolate and the underlying host defence defect is considered. PMID- 3111980 TI - Pooled specimens for Chlamydia trachomatis: new approach to increase yield and cost efficiency. AB - Pooled specimens from the urethra and cervix accounted for 97% of 101 positive chlamydial isolations in 332 women, and this yield compared favourably with the individual yield from either the urethra (77%) or the cervix (88%). Pooling specimens caused no apparent increase in toxicity to the cell culture system. These results indicate the advantages, in terms of higher yield and no higher cost, of combining the urethral and cervical specimens in one container. PMID- 3111981 TI - In vitro activity of 14 antimicrobial agents against Neisseria gonorrhoeae from Spain. PMID- 3111982 TI - Acquisition of cell-mediated immunity to Leishmania. I. Primary T-cell activation detected by IL-2 receptor expression. AB - In order to analyse the early stages of the T-cell response to Leishmania, bioassays for detecting low levels of IL-2 receptor expression both in bulk culture and under limiting dilution conditions have been used. Infection of C57BL/10 mice with Leishmania donovani amastigotes leads to the appearance of antigen-specific T lymphocytes bearing high-affinity IL-2 receptors 24-72 hr later. Phenotypic analysis by complement-mediated cytotoxicity indicates that these activated T cells comprise both L3T4+, Lyt2- and L3T4-, Lyt2+ populations. The data also suggest the existence of activated cells bearing both these markers. By both assay techniques, the appearance of receptor-positive populations appears transitory, with few such cells detectable at 7 days post infection. The implications of these data for further studies of murine leishmaniasis are discussed. PMID- 3111983 TI - The role of autoimmune phenomena in the pathogenesis of cataract. AB - Investigations were carried out to clarify the role of autoimmune phenomena in the pathogenesis of cataract in the adult human lens. Studies were carried out to determine the presence of serum antibodies to lens protein in patients with senile cataract, in patients with diabetes mellitus with and without cataract, and in healthy adult controls using the interfacial test and the gel-diffusion technique. Non-specific antibodies were removed by adsorption of sera with homogenized rat liver. A high proportion of healthy adults was found to have anti lens protein antibodies (44.4% by the gel-diffusion method). In contrast, patients with cataract and diabetic patients with no cataract demonstrated double this incidence (82% and 80%), while all diabetic patients with cataract showed the presence of antibodies (P = 0.0002). The possible causes for the development of lens antibodies in normal healthy humans are discussed. Also, the causes for the higher incidence of lens antibodies in patients with cataract and in diabetic subjects with no clinical evidence of cataract are considered in relation to cataract formation. Homogenates of cataractous lenses when investigated revealed the presence of both IgG and IgM immunoglobulins, the former probably to a greater extent. Fluorescent microscopy on cryosections of senile and diabetic cataractous lenses revealed the presence of immunoglobulins within the lens. The antigen in the immune complexes isolated from homogenized cataractous lenses was characterized by the SDS-polyacrylamide gel electrophoresis method. A single band was consistently obtained and the molecular weight of the protein was estimated to be between 35,000 and 40,000. The strong possibility of auto-antibodies to lens protein being of aetiological significance in the pathogenesis of cataract is discussed. PMID- 3111984 TI - Vaccines for the future--an update. PMID- 3111985 TI - Expression of genes in cloned murine cell lines that can be maintained in both interleukin 2- and interleukin 3-dependent growth states. AB - Two cloned murine cell lines, FD.C/1 and 32Dcl-23 exhibit switching of lymphokine dependent growth states. The bone marrow-derived FD.C/1 and 32Dcl-23 cell lines are normally grown in culture medium supplemented with interleukin 3 (IL3). The replacement of IL3 with interleukin 2 (IL2) in the medium results in an increase in IL2 receptor expression in FD.C/1 and 32Dcl-23 cells and the switching of cells to an IL2-dependent growth state. We have compared patterns of protein and phosphoprotein synthesis, as well as the expression of the c-abl, c-ras, c-myb, and c-fos oncogenes in these cell lines maintained in IL3- and IL2-dependent growth states. The synthesis of a series of proteins and phosphoproteins are identified with each of the lymphokine-dependent growth states. All of the oncogenes examined are expressed in both IL2- and IL3-dependent cells and are not altered by phenotypic changes in lymphokine growth dependence. The relationship of oncogene expression to intracellular pathways regulated by lymphokine-receptor interactions is considered. PMID- 3111986 TI - [Methods of identifying Neisseria gonorrhoeae]. PMID- 3111987 TI - IgM reassociation in the absence of J-chain. AB - Human monoclonal IgM pentamers with different biophysical properties (euglobulin, pseudoglobulin or cryoglobulin) were reduced and reassociated in the absence of J chain. Reassembly occurred for 50-82% of the monomers. The reassociated molecules consisted of covalent oligomers and pentamers. The deficiency of J-chain (estimated to be less than 0.17% of normal) was shown by alkaline-urea overloaded gel electrophoresis followed by silver staining. The addition of exogenous J chain, from polymeric IgA or IgM, did not significantly modify the reassembly ratio. Thus J-chain does not seem to be an absolute requirement for IgM polymerization. PMID- 3111988 TI - Allelic exclusion frequency analysis and molecular characteristics of immunoglobulins secreted by the hybridomas expressing both allelic genes. AB - The investigation of 750 B-lymphocyte hybridoma clones obtained by fusion of mouse myeloma and newborn heterozygous Igk-1a/Igk-1b rat splenocytes has revealed that 9.8% of Ig kappa-chain loci are rearranged productively. Seventeen hybridomas secrete kappa-chains of both allelic variants. The analysis of IgM molecules of 9 such clones demonstrated that in 6 cases only one L-chain allotype, either 1a or 1b, is present in IgM. Thus for the first time the high frequency of selective association of H and L chains in Ig-producing cells was shown. Evidently this selectivity may function as one of allelic exclusion mechanisms at the Ig assembly stage. PMID- 3111989 TI - Complexes of albumin and alpha 1-antitrypsin with Fc-fragment of IgA monomer are disulfide-bound to penultimate C-terminal cysteine in the C alpha 3-domain. AB - Six IgA myeloma sera, containing albumin (ALB)-IgA and alpha 1-antitrypsin (alpha 1-AT)-IgA complexes (CXs), were gel-filtered on Ultrogel AcA22. The CXs were eluted between monomeric and dimeric IgA. The CX-containing fractions were digested with three IgA-proteases: ALB and alpha 1-AT remained bound to Fc alpha , but not to Fab alpha-fragments. Short (less than 2 h) peptic digestion entirely released free ALB and alpha 1-AT from the CXs, indicating that these proteins are linked to the third constant domain of the alpha-chain. Identical results were obtained with anti-ALB immunosorbent-purified ALB-IgA CXs. Reduction-alkylation of ALB or alpha 1-AT bound to IgA or Fc alpha confirmed disulfide binding. The data support the binding of ALB and alpha 1-AT to the same penultimate C-terminal cysteine of the alpha-chain as that which binds the J-chain. PMID- 3111990 TI - Detection of CD1 positive cells in the peripheral blood of patients suffering from cancer-associated malnutrition. AB - The immunological phenotyping of peripheral blood mononuclear cells (PBMC) was assayed in a series of 22 patients suffering from severe cancer-associated malnutrition. A marked decrease of the T-lymphocyte subsets (CD3+, CD4+, CD8+) and of the CD20+ B lymphocytes occurred; there was however an increased percentage of monocytes but their absolute number was normal. Interestingly, 5% of the PBMC expressed "activated T-cell antigens". The specificity of two different monoclonal antibodies (MoAbs) towards CD1 epitopes (OKT6 and D47) was assessed by indirect immunofluorescence (IIF): about 5% of CD1+ thymocytes were detected with no antigen (Ag) cross reactivity with the small subset of activated T cells. It is hypothesized that some relationship may exist between such cells and malnutrition and/or cancer. PMID- 3111991 TI - Expression of HLA-DR antigens by thyroid cells: the effect of Graves' IgG. AB - We have investigated factors which influence HLA-DR expression on thyroid cells. While bTSH (100 mU/ml) did not enhance HLA-DR expression, it increased when brought about by IFN-gamma. Graves' IgG showed a dose-dependent (0.1-2 mg/ml) increase in DR expression and at a concentration of 2 mg/ml prolonged the time for which DR was expressed. The pathway of DR induction by Graves' IgG apparently differs from that by IFN-gamma. The humoral response in Graves' disease, by inducing DR expression, may be instrumental in propagating thyroid specific autoimmunity. PMID- 3111992 TI - Early experience with linear accelerator in carcinoma oesophagus middle third. PMID- 3111994 TI - T-independent form of azophenylarsonate fails to reveal "silent" idiotype positive B cells in idiotype-suppressed mice. AB - In three distinct chronic Ig-specific suppression systems in which suppression was initiated by injection of mice with anti-idiotype (Id) or anti-allotype sera, evidence has been presented by others that the differentiation of B cells bearing surface Ig with a target marker (Id or allotype) need not be totally disrupted. Normally "silent" Id+ B cells from Id-suppressed mice could be revealed by certain procedures, one of these being to make use of the powerful stimulatory properties of bacterial lipopolysaccharide. We have employed a similar strategy to determine whether cryptic CRIA+ B cells exist in significant numbers in hyperimmune, CRI-suppressed (HIS) A/J mice. Thus, following T cell removal, the Ar-specific B cell repertoire from HIS mice was probed using Ar- Brucella abortus as a T-independent Ag. No evidence for "silent" CRIA+ B cells was found. The results, taken in conjunction with those of others, suggests that there may exist multiple forms of long-term Ig-specific suppression. PMID- 3111993 TI - Duplication of J kappa genes within genus Rattus. AB - We have isolated a region containing the immunoglobulin kappa chain joining segments from a liver DNA library of the Australian rat Rattus villosissimus, and determined its nucleotide sequence. While the laboratory rat (Rattus norvegicus) had previously been shown to contain three recently duplicated copies of J kappa 2, R. villosissimus has only two. Furthermore, all three copies of J kappa 2 in R. norvegicus share an 11 bp deletion in their 5' flanking regions which is not evident in either copy of J kappa 2 in R. villosissimus. This suggests that the initial duplication events occurred separately in the two lineages, and were followed by a second duplication in R. norvegicus, all three duplications having occurred within the last 6-12 million years (although more complicated schemes involving gene conversion events cannot be excluded). These results indicate that there is a high degree of plasticity in this region of the genome, and that selective forces must exist which have maintained the number of expressible J kappa segments in humans (5) and rodents (4-6) within their narrow range. PMID- 3111995 TI - Surgical sustenance. PMID- 3111996 TI - Nasojejunal feeding following surgery for carcinoma of lower oesophagus. PMID- 3111997 TI - Sulphadiazine resistant strains of Neisseria meningitidis during an outbreak of meningococcal meningitis. PMID- 3111998 TI - Preliminary observations on immunologic phenotypes of non-Hodgkin's lymphoma in Indian subjects. PMID- 3111999 TI - In turning of coccyx--a deep rooted misconception for severe malnutrition. PMID- 3112000 TI - Nutrition and drug disposition. PMID- 3112001 TI - Impaired endothelium-dependent relaxations in rabbits subjected to aortic coarctation hypertension. AB - Rabbits were rendered hypertensive by suprarenal coarctation of the abdominal aorta. Seven days later, endothelium-dependent and endothelium-independent vascular relaxations were examined in vascular rings taken from hypertensive (thoracic aorta, carotid artery) and normotensive (abdominal aorta) regions. Relaxation of phenylephrine-contracted rings in response to endothelium-dependent agonists (acetylcholine, A23187) was impaired, compared with that in sham operated and intact controls, in regions exposed to the elevated blood pressure (i.e., above the coarctation). Responses to acetylcholine and A23187 in the abdominal aorta, below the coarctation, were not altered. The diminished endothelium-dependent responses in the thoracic aorta were not affected by pretreatment with the cyclooxygenase inhibitor indomethacin. In contrast to acetylcholine and A23187, responses to the endothelium-independent agonist nitroprusside were not attenuated in vessels from hypertensive regions, indicating that the defect occurred in the endothelium. The EC50 for acetylcholine-induced relaxations of thoracic aorta correlated significantly with mean arterial pressure above the coarctation, indicating that the extent to which endothelium-dependent relaxation is impaired is in proportion to the degree of blood pressure elevation. This study suggests that the diminished relaxations by endothelium-dependent agonists is a local response to the elevation of blood pressure and is not due to a circulating factor. PMID- 3112002 TI - [Randomized study comparing long-chain (LCT) and medium-chain (MCT) triglycerides as caloric carriers in postoperative nutritional therapy]. AB - The aim of the study was to investigate the effect of a new 20% fat emulsion, containing 50% MCT and 50% LCT in comparison to a 20% fat emulsion containing only LCT, in the postoperative period. The possible influence on nitrogen loss, protein synthesis and fat metabolism was estimated. 20 patients after elective colon surgery were included in the trial. Parenteral nutrition was carried out for 5 days with two isonitrogenic and isocaloric nutritional regimens including either MCT/LCT or only LCT fat emulsions. Fat emulsions were administered over a period of 12 h with a total fat supply rate of 0.12 g/kg B.W./h. Blood samples for determination of protein synthesis, triglyceride and ketone bodies were taken under fat infusion as well as before and after infusion. 24-h urine samples were taken to measure nitrogen balance. Our results showed no difference in protein levels between the MCT- and LCT group. The 5-day nitrogen balance showed a significant increase in the MCT group (p less than 0.05, Mann-Whitney U-test). At the end of the infusion period triglyceride levels in the MCT group (mean value 244 +/- 15 mg%) differed significantly compared to the LCT group (m = 190 +/- 24 mg%). 2 h later triglycerides in both groups fell to basal levels. beta Hydroxybutyrate (beta-HB) and aceto acetate (Ac-ac) concentrations showed significant differences between both groups. After 12 h infusion the MCT group had a mean level of 210 mumol/l beta-HB and 180 mumol/l Ac-ac vs. 90 mumol/l beta HB and 120 mumol/l Ac-ac in the LCT group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112003 TI - The metabolic response to glycerol during parenteral nutrition. AB - The use of various nonprotein energy sources in parenteral nutrition regimens has been discussed for many years. Besides glucose, glycerol, xylitol, fructose and sorbitol are currently being used as water-soluble parenteral fuels. Despite the increasing frequency with which these glucose substitutes are being used, little information is available regarding the differences they evoke in host responses. All experimental evidence to date has shown glycerol to be equally effective in sparing body nitrogen as glucose when supplied in hypocaloric amounts. Results from studies in injured animals suggest that exogenously administered glycerol is a more potent inhibitor of fatty acid oxidation than glucose. Although results from human volunteers have been variable, glycerol administration after injury appears to markedly reduce fatty acid oxidation and ketogenesis, as well as increase hepatic glycogen. Glycerol toxicity appears to result only from its excessive administration, or when administered intraperitoneally or subcutaneously. Intravenous administration of hypocaloric quantities of glycerol alone or as a component of total parenteral nutrition is safe and effective. PMID- 3112004 TI - [Limits of the extensive use of glucose as infusion carbohydrate in parenteral nutrition]. AB - The limiting factors for parenteral nutrition with glucose are indicated by the metabolic states of the patients. The rate of glucose utilization is mainly restricted by the degree of insulin resistance which may be localized at the receptor (down regulation, tyrosine kinase?) or at the postreceptor (mediators? Randle-mechanism) level. Usually, clear data about the rate of glucose production in the liver and glucose utilization in the peripheral organs are lacking, and therefore the glucose infusion rate cannot be calculated individually. The glucose infusion rate is usually adapted by monitoring the glucose and insulin levels in the patients; furthermore, insulin-resistant states may be detected by these parameters. As glucose is a main energy source in parenteral nutrition, up to 500 mg glucose/kg B.W./h may be infused in addition to a recommended amount of amino acids and lipid emulsions. Permanent infusion of glucose (over 24 h) is metabolically not adequate, since permanent hyperglycemia and hyperinsulinemia may lead to lipid deposition in the liver. In insulin-resistant states with hyperglycemia glucose infusion rates are limited and should be carefully adapted. Under these circumstances, glucose may be partly replaced by xylitol and sorbitol. Still unanswered is the question of whether the limited glucose utilization rate should be increased by therapeutic interventions. The elimination of insulin-resistant states should be useful in the postaggression syndrome. This therapeutic regimen would also promote protein and lipid synthesis. Since insulin is a main anabolic hormone, its optimal action should be restored as soon as possible. PMID- 3112005 TI - [Carbohydrate intolerance as a danger in infusion therapy]. AB - The following types of carbohydrate intolerance are discussed as a risk in infusion therapy: Hereditary fructose intolerance, fructose-1,6-biphosphatase deficiency, impairment of glucose utilization during the post-aggression syndrome and/or in latent or overt diabetes mellitus. Asking about symptoms of fructose intolerance has to be part of every routine anamnesis. Application of any kind of carbohydrate requires differential therapeutic considerations. Undiscovered fructose intolerance is more likely the younger the patient is, whereas the frequency of glucose intolerance increases with age. In unconscious patients without anamnesis, fructose or sorbitol should not be applied. Never should an attempt be made to compensate falling blood glucose levels under infusion therapy by application of fructose or sorbitol. As carbohydrate addition to routine fluid and electrolyte substitution xylitol in the specified low dosage is without risk in a diabetes-like metabolic condition as well as in fructose intolerance. PMID- 3112007 TI - [Fructose and sorbitol as energy-supplying substrates for parenteral nutrition]. AB - The glucose substitutes (fructose, sorbitol, xylitol) have significant metabolic advantages in stress situations as compared to glucose. Side-effects are usually not to be expected if indications and dosage are carefully determined. The only contraindication for fructose and for sorbitol is hereditary fructose intolerance. However, this metabolic disease should be known to physicians who are involved in parenteral nutrition. Fructose intolerance might also be diagnosed by the metabolic alterations caused by fructose or by sorbitol administration in such patients. It was shown repeatedly during the last few decades that glucose formed in the liver during metabolism of glucose substitutes and delivered to the circulation is obviously metabolized without an increase in blood glucose concentration and without additional requirement of insulin. No explanation for this amazing, long-observed metabolic effect is known to date. These reproducible results should stimulate new investigations. Such effects should not be rejected or questioned because they do not fit into the hypotheses. PMID- 3112006 TI - [Intravenous feeding--possibilities and limits in the use of glucose and xylitol following trauma and infection, with special reference to liver metabolism]. AB - Numerous side-effects of intravenously administered substrates have taught us that we have to reevaluate the dosages of the various substitutes of an intravenous regimen after trauma and during sepsis, whereby the limitation of glucose calories to approx. 3 g/kg B.W./day is of great metabolic importance. Additionally required calories can be provided either in the form of a lipid emulsion in a dosage of 1 to maximally 1.5 g/kg B.W./day and/or additionally xylitol in a dosage of max. 3 g/kg B.W./day. PMID- 3112008 TI - Mechanisms of platelet aggregation by viridans group streptococci. AB - The direct aggregation of platelets is thought to be an important event in the pathogenesis of viridans streptococcal endocarditis, but the mechanisms for platelet activation are unknown. We evaluated the processes by which two endocarditis-producing strains of viridans group streptococci activated human platelets in vitro, as measured by platelet cyclooxygenase activity, secretion, and aggregation. Addition of either streptococcal strain to platelets suspended in whole plasma resulted in a mean lag phase of 15.3 min, followed by platelet secretion and brisk aggregation. The lag phase duration was dependent on the platelet donor and appeared to be a function of direct platelet-bacterial interaction. Aggregation was partially inhibited by 20 muM [corrected] indomethacin and blocked completely by 1 mg of apyrase, an extracellular ADP hydrolase, per ml. Neither strain aggregated washed platelets suspended in Tyrode solution alone. However, both strains produced maximal aggregation when the platelet suspension was supplemented with 10% (final concentration) normal plasma. Studies with factor-deficient plasmas demonstrated that exogenous fibrinogen was required for aggregation. One or more additional plasma components were needed, which eluted with a molecular weight of 67,000 to 130,000 on gel permeation chromatography. These cofactors have not been described for other platelet agonists, which suggests that viridans streptococci may aggregate human platelets by a novel mechanism. PMID- 3112009 TI - Urease inhibition by EDTA in the two varieties of Cryptococcus neoformans. AB - Cryptococcus neoformans var. neoformans (74 isolates) and C. neoformans var. gattii (44 isolates) were used to test urease activity after growth on both yeast extract-glucose-peptone agar (YEPG) and on YEPG supplemented with 100 microM EDTA. Every isolate grown on YEPG agar for 48 h at 30 degrees C produced a positive reaction within 1 h in a modified rapid urease assay at 37 degrees C. However, isolates grown on YEPG with 100 microM EDTA showed a distinct pattern which corresponded to their varietal status. All but 1 of 74 C. neoformans var. neoformans isolates (98.7%) produced a positive reaction within 1 to 4 h, while none of 44 C. neoformans var. gattii isolates produced a positive reaction within the same period. The urease inhibition results and the canavanine-glycine bromthymol blue agar test results showed 100% correlation among isolates of C. neoformans var. gattii and 98.7% correlation among isolates of C. neoformans var. neoformans. Two representative isolates of C. neoformans var. gattii (serotypes B and C) were further tested for urease during a prolonged incubation period in urea broth. These isolates failed to show a positive reaction even after 11 h of incubation. The uptake of EDTA was negligible in the two varieties. Extracts of cells grown on YEPA agar showed a high level of urease activity in both varieties. Extracts of cells grown on the agar with 100 microM EDTA showed a marked reduction (86%) of urease activity in one isolate of C. neoformans var. gattii but showed only a 30% reduction in one isolate of C. neoformans var. neoformans. Based on these results, the differential effect of EDTA on the two varieties of C. neoformans appeared to be due to greater inhibition of urease synthesis in C. neoformans var. gattii. PMID- 3112011 TI - The principal protein antigens of isolates of Mycoplasma pneumoniae as measured by levels of immunoglobulin G in human serum are stable in strains collected over a 10-year period. AB - To determine whether antigenic variation in protein antigens of Mycoplasma pneumoniae occurred over time, 12 isolates obtained from pneumonia patients over a 10-year period (1964 to 1974) were compared by immunoblotting (Western blotting) against acute and convalescent human serum samples obtained from the same patients. The strains selected were isolated from patients who had low anti lipid complement-fixing antibody titers in their acute-phase serum samples and high titers in their convalescent-phase serum samples. The polypeptide composition of the strains was closely similar by protein staining even when compared with prototype FH-Liu. On immunoblotting, all strains showed five bands (170, 130, 90, 45, and 35 kilodaltons [kDa]) which were stained more intensely by convalescent-phase than by acute-phase specimens. A sixth band (62 kDa) was detected by the conjugate alone. In FH-Liu, one band (110 kDa) was prominently stained by convalescent-phase specimens; this band was much less apparent in all of the clinical isolates. Two isolates possessed an additional band (92 kDa) which was stained more prominently by some but not all convalescent-phase specimens. Because of its known antigenic relationships and culture similarities, Mycoplasma genitalium was used for comparison. More polypeptides of M. genitalium than of M. pneumoniae were recognized by acute-phase serum samples, and 4 of 12 convalescent-phase serum samples showed increases in antibodies to certain M. genitalium polypeptides. However, these reactive polypeptides did not correspond in molecular mass to polypeptides recognized in M. pneumoniae; thus the signature profile of human convalescent-phase specimens with M. pneumoniae was distinct. These five polypeptides, individually or in combination, are especially promising for use in detection of human serum antibodies by enzyme-linked immunosorbent assay because they were found in all M. pneumoniae isolates tested. PMID- 3112010 TI - Physical heterogeneity of neisserial lipooligosaccharides reflects oligosaccharides that differ in apparent molecular weight, chemical composition, and antigenic expression. AB - We studied the oligosaccharides (OS) of outer membrane lipooligosaccharides (LOS) of Neisseria gonorrhoeae and Neisseria meningitidis. OS from the LOS of an individual neisserial strain always eluted from Sephadex G-50S as multiple peaks; the polyacrylamide gel elution profiles were nearly identical to the polyacrylamide gel electrophoresis profiles of the sodium dodecyl sulfate disaggregated native LOS from which the OS were derived. Neisserial OS coeluted with Dex14 to Dex27 dextran oligomers (Mr, 2,210 to 4,320). Monosaccharide composition varied among the several OS released from the LOS of a single strain. The two OS of a gonococcal strain sensitive to normal human serum (NHS) bacteriolysis (sers) varied in their ability to inhibit the binding of NHS immunoglobulin M to their parental LOS. The OS that was rich in hexosamines inhibited NHS immune lysis of its parent strain; the OS that was poor in hexosamines did not. We conclude that structural differences in their OS account for the Mr heterogeneity of the LOS of a strain. PMID- 3112013 TI - Mechanical transmission of Bacillus anthracis by stable flies (Stomoxys calcitrans) and mosquitoes (Aedes aegypti and Aedes taeniorhynchus). AB - We evaluated the potential of stable flies, Stomoxys calcitrans, and two species of mosquitoes, Aedes aegypti and Aedes taeniorhynchus, to transmit Bacillus anthracis Vollum 1B mechanically. After probing on Hartley guinea pigs with a bacteremia of ca. 10(8.6) CFU of B. anthracis per ml of blood, individual or pools of two to four stable flies or mosquitoes were allowed to continue feeding on either uninfected guinea pigs or A/J mice. All three insect species transmitted lethal anthrax infections to both guinea pigs and mice. Both stable flies and mosquitoes transmitted anthrax, even when they were held at room temperature for 4 h after exposure to the bacteremic guinea pig before being allowed to continue feeding on the susceptible animals. This study confirms that blood-feeding insects can mechanically transmit anthrax and supports recent anecdotal reports of fly-bite-associated cutaneous human anthrax. The potential for flies to mechanically transmit anthrax suggests that fly control should be considered as part of a program for control of epizootic anthrax. PMID- 3112012 TI - Type II heat-labile enterotoxin of Escherichia coli activates adenylate cyclase in human fibroblasts by ADP ribosylation. AB - Type II heat-labile enterotoxin (LT-II) from Escherichia coli causes characteristic morphological changes and accumulation of cyclic AMP in Y-1 adrenal cells, but it is not neutralized by antisera against choleragen (CT) or the classical type I heat-labile enterotoxin (LT-1) from E. coli. The action of purified LT-II on CT- and LT-I-responsive human fibroblasts was investigated and compared with that of CT. Fibroblasts incubated with LT-II or CT had an increased cyclic AMP content as well as a fourfold elevation of membrane adenylate cyclase activity. In membranes, activation of cyclase by toxin was enhanced by NAD, GTP, and dithiothreitol. The effect of LT-II on intact fibroblasts or membranes was increased by trypsin treatment of toxin. Since activation of adenylate cyclase by LT-II was stimulated by NAD, the ability of LT-II to catalyze the [32P]ADP ribosylation of membrane proteins in the presence of [32P]NAD from control and LT II- and CT-treated fibroblasts was investigated. Similar proteins were [32P]ADP ribosylated in membranes exposed to LT-II or CT; LT-II- and CT-specific labeling was significantly decreased in membranes prepared from cells preincubated with either LT-II or CT. These studies are consistent with the hypothesis that LT-II, similar to CT and LT-I, increases cyclic AMP by activating adenylate cyclase through the GTP-dependent ADP-ribosylation of specific membrane proteins. PMID- 3112014 TI - Response of inbred mice to aerosol challenge with Mycobacterium tuberculosis. AB - An autosomal dominant gene (Bcg), which maps to mouse chromosome 1, has been shown to confer on mice resistance to attenuated Mycobacterium bovis BCG Montreal, Salmonella typhimurium, and Leishmania donovani. Most animal models used for the study of the Bcg gene have involved intravenous injection of a large number of microorganisms (greater than 10(4) CFU). The present study examines the effect of the Bcg gene on the resistance of inbred mice to challenge via the respiratory route with 5 to 10 CFU of virulent Mycobacterium tuberculosis. The number of tubercle bacilli recovered from the lung lobes indicates that the growth kinetics of the microorganism did not differ between BCG-resistant and BCG susceptible strains of mice. The number of tubercle bacilli recovered from the spleen was also similar among strains. Although there were reproducible differences in the time of first recovery of bacilli from the spleen, these differences appeared to be unrelated to the expression of the Bcg gene. When mice were challenged with purified protein derivative, all strains responded similarly as observed by measurements of footpad swelling. PMID- 3112015 TI - Purification of Clostridium difficile toxin A by affinity chromatography on immobilized thyroglobulin. AB - An efficient, single-step method for isolating highly purified toxin A from Clostridium difficile culture filtrates is described. The purification procedure was based on the affinity binding and release of toxin A to bovine thyroglobulin conjugated to agarose beads. The toxin strongly bound at 4 degrees C to the carbohydrate binding determinant Gal alpha 1-3Gal beta 1-4GlcNAc, a carbohydrate sequence which occurs on bovine thyroglobulin. Toxin bound to thyroglobulin at 4 degrees C, allowing its separation from the culture filtrate and contaminating proteins during the purification scheme. The toxin was eluted by increasing the temperature to 37 degrees C. The toxin-binding capacity was related to the amount of thyroglobulin immobilized on the gel: an affinity column containing 15 mg of bovine thyroglobulin per ml of gel bound 0.53 mg of toxin A per ml of gel. The percent recovery of purified toxin ranged from 56 to 80% and was inversely related to the amount of thyroglobulin coupled to the gel. The affinity-purified toxin was homogeneous as judged by crossed immunoelectrophoresis and gradient polyacrylamide gel electrophoresis and was immunologically identical to toxin A purified by conventional methods as determined by immunodiffusion analysis. The biochemical, hemagglutinating, and toxic properties of the toxin were preserved after affinity chromatography and were comparable with those of toxin A purified by conventional methods. PMID- 3112016 TI - Genetic association of defects in macrophage larvicidal activity and vaccine induced resistance to Schistosoma mansoni in P strain mice. AB - In contrast to most inbred strains, P mice fail to develop significant resistance to Schistosoma mansoni infection as a result of vaccination with irradiated cercariae. Vaccinated P mice also exhibit a defect in macrophage activation for killing of larval schistosomes upon specific-antigen challenge in vivo. To examine the genetic basis of these defects in vaccine-induced immunity, inheritance of the two traits was examined in (C57BL/6 X P)F1, F2, and reciprocal backcross generations. The defect in macrophage function which characterizes the P strain parent was found to be inherited in a fully recessive manner and to be controlled by only one or two major genetic loci. Moreover, a highly significant correlation (P less than 0.0025) was observed between the level of macrophage larvicidal activity and the level of resistance to challenge infection in segregating generations. Such an association is consistent with a cause-and effect relationship, providing strong in vivo evidence implicating activated macrophages as immune effector cells of resistance to S. mansoni in the mouse irradiated-vaccine model. PMID- 3112017 TI - Resistance to meningococcemia apparently conferred by anti-H.8 monoclonal antibody is due to contaminating endotoxin and not to specific immunoprotection. AB - We evaluated the ability of a monoclonal antibody directed against the common H.8 antigen of pathogenic Neisseria sp. to confer passive protection against meningococcal disease in mice. The apparent protection conferred by antibody purified from tissue culture supernatant was actually the result of endotoxin contamination of buffers and tissue culture media. Endotoxin-free anti-H.8 antibody was not protective. The possibility of endotoxin contamination should be considered when evaluating immunity conferred by passively administered antibody in animal models. PMID- 3112018 TI - [Significance of Pseudomonas aeruginosa virulence factors for acute and chronic Pseudomonas aeruginosa infections]. AB - The virulence of Pseudomonas aeruginosa is multifactorial and caused by several extracellular enzymes and other substances. The importance of these virulence factors for the pathogenesis of human P. aeruginosa infections is dependent on the type of infection. For acute, systemic infections in immunocompromised patients, exotoxin A, alkaline protease and elastase are essential virulence factors. In localized infections (e. g., cystic fibrosis) they seem to be of minor importance, since they are neutralized by specific antibodies in immune complexes, and in the case of exotoxin A cleavage by proteinases from polymorphonuclear leukocytes occurs. The rhamnolipid of P. aeruginosa which has been detected in sputa of patients with cystic fibrosis evades the host's immune response and has to be regarded as a potential virulence factor together with the phenazine pigments, also in chronic P. aeruginosa infections. PMID- 3112019 TI - [Effect of Pseudomonas immunoglobulin on the antibacterial activity of human phagocytes]. AB - The in vitro influence of a pseudomonas immunoglobulin in active and inactivated serum on the bactericidal activity and phagocytosis of human polymorphonuclear leukocytes was evaluated against Pseudomonas aeruginosa. No lysis of the bacteria could be found in either serum, however, the bactericidal activity of the leukocytes was significantly enhanced in active serum (p less than or equal to 0.05), whereas no effect was measurable in inactivated serum. Phagocytosis could be increased in concentrations of 10% immunoglobulin, (equivalent to 5 mg IgG/ml); however, a concentration of 15% showed a lower phagocytosis index which was comparable to that in the 5% preparation. This immunoglobulin proved to be able to support the bacterial phagocytosis and killing of P. aeruginosa by human polymorphonuclear leukocytes in vitro. PMID- 3112020 TI - [Pseudomonas aeruginosa immunoglobulin in experimental pneumonia]. AB - A guinea pig model of experimental Pseudomonas aeruginosa pneumonia was used to evaluate factors affecting the efficacy of passive immune therapy with Psomaglobin N, a hyperimmune P. aeruginosa globulin. Animals treated 2 h after infection with a single intravenous infusion of Psomaglobin N, 500 mg/kg, demonstrated 33% survival. Lower dosages were less effective and no survivors occurred among albumin-treated controls. Treatment with Psomaglobin N was effective if given 2 h or 8 h after infection but not if delayed until 24 h after infection. Animals rendered neutropenic with cyclophosphamide did not survive if treated with Psomaglobin N alone. However, when Psomaglobin N was added to tobramycin treatment, a significant increase in survival occurred (86%) as compared to that observed with tobramycin alone (43%) (p less than 0.05). We conclude that Psomaglobin N may offer a useful therapeutic option in management of P. aeruginosa pneumonia. PMID- 3112022 TI - [Pseudomonas aeruginosa as a pathogen in opportunistic infections]. AB - Pseudomonas aeruginosa, in spite of being an ubiquitous microorganism, rarely colonizes healthy individuals. Hospitalization, as well as the length of time spent in hospital, significantly increase the rate of colonization, especially in immunocompromised patients. Antibacterial chemotherapy or prophylaxis together with invasive diagnostic procedures favour colonization and infection with P. aeruginosa. Immune deficiencies and adverse interactions of P. aeruginosa with the immune system facilitate infection. Thus, a number of exogenous as well as endogenous factors and their interactions favour infection of patients with P. aeruginosa. PMID- 3112021 TI - [Prevention of gram-negative and gram-positive infections with 3 intravenous immunoglobulin preparations and therapy of experimental polymicrobial burn infection with intravenous Pseudomonas immunoglobulin G and ciprofloxacin in an animal model]. AB - Three immunoglobulin preparations for intravenous infusion were compared in vivo to determine their relative protective capacity against several gram-negative and gram-positive pathogens. Polyglobin N is a conventional IgG concentrate. Psomaglobin N is identical in formulation to Polyglobin N but is prepared from the plasma of donors who have naturally high levels of antibody to lipopolysaccharide antigens of Pseudomonas aeruginosa. IgGMA is a conventional IgG concentrate containing 12% IgG and 16% IgA. In a murine model of burn wound sepsis the three IgG preparations were similarly protective against three or ten strains of P. aeruginosa. Psomaglobin N and Polyglobin N were significantly (p less than or equal to 0.015) more protective than IgGMA against six of ten and three of ten strains of P. aeruginosa, respectively. In a murine model of Streptococcus pneumoniae type 3 pneumonia, the three Ig preparations were similarly protective. IgGMA was significantly more protective (p less than or equal to 0.025) than Psomaglobin N and Polyglobin N against Salmonella typhimurium in murine peritonitis. However, the mean protective dose (PD50) of the two later preparations was less than or equal to 20 mg/kg body weight. In models of peritonitis both Psomaglobin N and Polyglobin N were more protective than IgGMA (p less than or equal to 0.004) against Haemophilus influenzae b, Klebsiella pneumoniae, Serratia marcescens 06:H3 and group B Streptococcus types 1b and 1c. Psomaglobin N and ciprofloxacin were employed to treat established polymicrobial murine burn wound sepsis resulting from contamination of the burn site with mixtures of P. aeruginosa and Staphylococcus aureus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112023 TI - [Experiences with a Pseudomonas immunoglobulin in ventilated patients with Pseudomonas pneumonia in a surgical intensive care station]. AB - In a clinical trial, the efficacy of a Pseudomonas immunoglobulin was studied in ten ventilated patients suffering from Pseudomonas pneumonia. Compared to ten patients of a previous study who had received a polyvalent immunoglobulin (control group), patients treated with Pseudomonas immunoglobulin fared better with respect to clinical success and duration of treatment, the period of antibiotic treatment being significantly shorter than in the control group. PMID- 3112024 TI - [Use of pseudomonas immunoglobulin in ventilated patients at an interdisciplinary surgical intensive care station]. AB - The clinical efficacy and safety of a new pseudomonas hyperimmune globulin for intravenous administration were examined in 30 patients in a prospective randomized study. Although the statistical evaluation of the measurable parameters did not show relevant differences between the therapy group (n = 15) and the controls (n = 15), the clinical course of the disease was markedly better in patients treated with hyperimmune globulin. In the control group, three patients died from Pseudomonas aeruginosa infections, but none in the therapy group. The preparation was very well tolerated. PMID- 3112026 TI - Botrytis cinerea: a study of the immunological properties during growth. Incidence of antibodies against B. cinerea in a group of patients with aspergillosis. AB - When growing Botrytis cinerea in Sabouraud medium, different phases of growth could be recognized using pH, mycelium yield, and culture filtrate antigens as parameters of growth. Immunological characteristics of the different phases (early, intermediate, and late) of growth were measured using IgE and IgG binding by enzyme allergosorbent test and enzyme-linked immunosorbent assay, respectively, and quantities of precipitating components (double immunodiffusion and rocket immunoelectrophoresis). The number of precipitating components was maximal in culture filtrate extracts during late phase (III) of growth. In contrast, both IgE and IgG binding were already maximal in the early phase of growth (9 days of cultivation). In a group of patients with elevated IgE antibodies against Aspergillus fumigatus, about half of them also showed elevated IgE antibodies against B. cinerea. This indicates that multiple exposition is a cause of multiple sensitization; however, cross-reactivity in some of these sera cannot be excluded. PMID- 3112025 TI - [Pseudomonas immunoglobulin prophylaxis in patients with burn injuries]. AB - Pseudomonas aeruginosa belongs to the most frequent pathogens isolated from patients with burns. In a mouse model for artificial burns it was found that prophylactic administration of a hyperimmune globulin with antibody titres against P. aeruginosa (Fisher immunotypes 1, 2, 4 and 6) reduced mortality. Therefore, the prophylactic administration of Pseudomonas immunoglobulin was examined in a prospective randomized study in two groups of 13 patients each. Severely burned patients with at least second degree burns over 30% to 70% of the total body surface area received 250 mg Pseudomonas immunoglobulin/kg body weight by the intravenous route between days 3 and 13. After treatment, plasma IgG levels were significantly raised between days 7 and 16 as compared to the controls, yet the incidence of infections caused by P. aeruginosa was not reduced. However, only two of the six infected patients, developed septicaemia, whereas in the control group, local Pseudomonas infection led to septicaemia in five out of seven patients. The number of septicaemic Staphylococcus aureus infections was also lower in patients on immunoglobulin prophylaxis, with two cases compared to four cases in the control group. Due to the limited number of cases studied, statistically significant results could not be obtained, however, there was a positive trend in favour of Pseudomonas immunoglobulin treatment. PMID- 3112027 TI - Recurrence of an allergic inflammation of air-pouch type in rats and possible participation of prostaglandin E2. AB - The recurrence of allergic inflammation, as examined by exudate accumulation, infiltration of polymorphonuclear leukocytes into the exudate, edema formation, vascular permeability and prostaglandin E2 levels in the exudate, was induced by injecting the antigen, azobenzene arsonate-conjugated acetyl bovine serum albumin, into the capsule of the proliferative granulation tissue which had been formed by the first-time antigenic challenge injection into an air pouch in the dorsum of the sensitized rat. The recurrence of the allergic inflammation 4 and 24 h after the antigenic challenge was inhibited dose-dependently by treatment with cyclooxygenase inhibitors, suggesting the possible participation of cyclooxygenase products, especially prostaglandin E2. The difference in the allergic inflammatory responses induced by the first-time antigenic challenge and the second-time antigenic challenge was discussed from the viewpoint of chemical mediators. PMID- 3112028 TI - Testicular function in eight patients with seminoma after unilateral orchidectomy and radiotherapy. AB - Testicular function was monitored in eight patients with low stage seminoma who were treated with radiotherapy following unilateral orchidectomy. The absorbed gonadal radiation dose ranged from 15 to 157.5 rad. At 10-24 months after radiotherapy, serum hormone levels, sperm analysis, sperm penetration into zona free hamster ova (HOP-test) and lymphocyte chromosome abnormalities were evaluated. Two patients were azoospermic with elevated serum levels of LH and FSH. The remaining six patients had slightly decreased (n = 3) or normal (n = 3) seminal parameters. Their HOP rates were within the normal range. A low incidence of polyspermy (i.e. only one penetrating sperm per ovum) was found in the patients, suggesting low penetrability of motile sperm. A highly significant correlation was found between sperm count or sperm penetrability and time post irradiation. The results indicate that restitution of testicular function is time dependent. PMID- 3112029 TI - Plasma reproductive hormones in normal and vasectomized Chinese males. AB - Plasma reproductive hormones (testosterone, LH, FSH and prolactin) were measured in 298 normal healthy males aged 30-73 years from rural areas of Sichuan Province, People's Republic of China, and in 505 similar men vasectomized between 1 year and 25 years previously. Age-related increases in LH and FSH but not in testosterone or prolactin were noted in normal men. No adverse effects of vasectomy were observed apart from a 16% increase in mean LH levels in the vasectomized compared to non-vasectomized men of similar ages. PMID- 3112030 TI - Comparison of glycosidase levels in bovine seminal plasma. AB - Seven glycosidases (beta-N-acetylglucosaminidase, alpha-fucosidase, beta galactosidase, acid alpha-glucosidase, beta-glucuronidase, acid and neutral alpha mannosidase) were analysed in seminal plasma from the first and second successive ejaculates in normal Ayrshire bulls. In comparison to our previous data the results indicate that beta-N-acetylglucosaminidase, beta-galactosidase and beta glucuronidase are derived mainly from epididymal secretions, while alpha fucosidase and particularly neutral alpha-mannosidase originate additionally from the spermatozoan cytoplasmic droplets. The seminal vesicles appear to contribute particularly to the seminal plasma acid alpha-glucosidase and acid alpha mannosidase activities. The seminal plasma enzymes derived from the epididymis and cytoplasmic droplets were suppressed in semen samples with low sperm density or with high numbers of abnormal spermatozoa. The epididymal and seminal vesicle enzymes could be utilized in assessment of the secretory/functional capacity of these glands. PMID- 3112031 TI - Clonal rearrangements of T-cell receptor and immunoglobulin genes and immunophenotypic antigen expression in different subclasses of Hodgkin's disease. AB - Twenty-two cases of Hodgkin's disease (HD), representing the 4 different subclasses, were studied by immunophenotypic and immunogenotypic analysis. Quantitative immunophenotypic analysis of HD infiltrates showed a predominance of CD3-positive T cells in all subtypes except the lymphocytic depletion (HDLD) subtype. Only 5 samples of HD [2 of lymphocytic predominance (HDLP), 2 of mixed cellularity (HDMC), and one of nodular sclerosis type (HDNS)] were found to have both their Ig and T-cell antigen receptor (TcR) genes in the germ-line configuration. The remaining patients with HDLP (3 cases), HDNS (5 cases), and HDMC (4 cases), all exhibited rearrangements of either TcR gamma or TCR gamma and TcR beta genes, while all 5 cases of HDLD had either TCR gamma or immunoglobulin heavy-chain gene rearrangement. These results substantiate the view that Hodgkin's lymphomas contain clonal lymphocyte populations and that different rearrangement patterns may be associated with different subclasses of HD. PMID- 3112032 TI - Phenotype versus immunoglobulin and T-cell receptor genotype of Hodgkin-derived cell lines: activation of immature lymphoid cells in Hodgkin's disease. AB - Three Hodgkin-derived cell lines (L428, L540, and CO) were studied for rearrangements and expression of immunoglobulin and T-cell receptor genes, and their genotype was compared to the phenotype. As far as the genotype is concerned, all 3 cell lines have characteristics of lymphoid cells; L428 of B, and L540 and CO of T-cell origin. L428 cells have one Ig heavy chain allele rearranged to C gamma and transcribed into RNA, while the second is deleted. Furthermore, L428 cells show an unusual immunoglobulin kappa light chain gene rearrangement involving deletion of the kappa constant gene in one allele, while the remaining kappa and lambda loci are in germline configuration. L540 and CO have, in contrast to L428 cells, the immunoglobulin genes in germline and T-cell receptor genes rearranged. The T-cell receptor beta and gamma genes are rearranged in both L540 and CO, whereas a rearrangement in the alpha locus was detected in L540 cells only. RNA of the size of functional beta chain transcripts was found in CO cells and of the size of functional alpha chain transcripts in L540 cells. All 3 cell lines are classified as immature lymphoid cells with respect to the limited expression of B- and T-cell antigens, respectively, and to the incomplete expression of their antigen receptor. The immaturity of lymphoid differentiation contrasts with the expression of activation antigens, i.e. Ki-1, Ki-24, HLA-DR, and IL-2 receptor. The immaturity of the cells excludes the possibility that the cells were activated along the physiological pathway, i.e. by interaction of the cell with antigen. The results obtained on the cell lines are in accordance with in vivo studies and suggest that Hodgkin and Sternberg Reed cells are immature lymphoid cells which are activated by a still unknown mechanism. PMID- 3112033 TI - The effects of immunomodulating peptidoglycan monomer and muramyl dipeptide on hepatic microsomal UDP-glucuronyltransferase and beta-glucuronidase. AB - The effects of immunomodulating peptidoglycans, peptidoglycan monomer (PGM) and muramyl dipeptide (MDP), on hepatic microsomal UDP-glucuronyltransferase (uridine diphosphoglucuronate glucuronosyl transferase, EC 2.4.1.17) and beta glucuronidase (beta-D-glucuronide glucuronohydrolase, EC 3.2.1.31) were tested in female C57Bl mice. 4-Methylumbelliferone and p-nitrophenol were used as representative substrates for one functional form of UDP-glucuronyltransferase (GT1) and testosterone for the second functional form (GT2) of the enzyme. Both PGM and MDP were found to transiently inhibit the activity of UDP glucuronyltransferase. There was no significant difference in the magnitude of inhibition of the two functionally different enzyme forms. The activity of microsomal beta-glucuronidase was tested using 4-methylumbelliferyl glucuronide and p-nitrophenyl glucuronide as substrates. Time dependent transient inhibition of beta-glucuronidase activity was observed with both peptidoglycans. In addition, the effect of MDP on cytochrome P-450 was tested, since we have shown previously that PGM affected this system. MDP decreased the content of cytochrome P-450 and inhibited the activity of related enzymes. PMID- 3112034 TI - Tissue plasminogen activator in the trabecular endothelium. AB - By quantitative analysis of tissue plasminogen activator (TPA) in the trabecular endothelium, corneal endothelium, and iris in the eyes of monkeys and dogs, we found significant levels of TPA activity. In a [125I]fibrin-coated well assay, the levels for the dog and monkey were, respectively: trabecular endothelium, 0.2 and 0.5; corneal endothelium, 0.8 and 0.5 IU per mg protein. The iris tissue showed high TPA activity, but its protein content could not be measured with the techniques employed. Activity in the aqueous humor was not detectable. By the ELISA technique, the values (in ng TPA/mg tissue protein) for the dog and monkey were, respectively: trabecular endothelium, 0.16 and 0.44; corneal endothelium, 0.48 and 0.92. Again, iris tissue showed high TPA activity, whereas the aqueous humor showed low activity (0.86 ng/ml). The data obtained with the two methods showed a reasonable consistency, although a direct comparison was not possible because two separate standards were used. The presence of TPA in the trabecular endothelium, corneal endothelium, and iris may be important in modulating the resistance to aqueous outflow under normal conditions as well as those of hyphema. PMID- 3112035 TI - Primary pulmonary hypertension: treatment with heart-lung transplantation. PMID- 3112036 TI - Poly(ADP-ribose)synthetase from HeLa cell nuclei: purification and properties. AB - Poly(ADP-ribose)synthetase has been purified over 600-fold from HeLa cell nuclei. Upon electrophoresis on 9% polyacrylamide slab-gel in the presence of SDS, the purified enzyme resolved in two bands that showed similar apparent Mr values, 110,000 and 118,000. The aminoacid composition of the two components differed from compositions reported for the same enzyme from other sources. In accordance with other reports, the enzyme purified from HeLa cell nuclei exhibited an absolute dependence on DNA and its activity was modulated by changes in the histone concentration. Incubation of intact nuclei from HeLa cells with [14C]NAD resulted in the isolation of a poly(ADP-ribose)synthetase to which a definite radioactivity is bound. These results are taken as a further demonstration that the enzyme can be auto-ADP-ribosylated. PMID- 3112037 TI - Utilization of selenalysine by thialysine resistant CHO cells. PMID- 3112038 TI - Clearance of maltose administered at different infusion rates. AB - Maltose is a disaccharide consisting of 2 molecules of d-glucose which at 10% solution is isotonic with plasma but provides a caloric supply double than glucose. Its possible use in total parenteral nutrition was investigated. Two homogeneous groups of patients were infused during a 2-hour period with a 10% maltose solution at 0.2 g/kg/h and at 0.4 g/kg/h flow rate. The data collected during and at the end of infusion demonstrate that: 1) the major metabolic parameters do not undergo significant alterations after maltose infusion; 2) the infusion at 0.4/kg/h causes an osmotic diuresis that does not significantly affect the water-electrolyte balance of the patients. Nevertheless it is not possible to exclude that this condition may lead to negative side-effects in critical patients; 3) the urinary excretion of maltose and glucose is significantly higher in the group of patients with 0.4 g/kg/h infusion rate. PMID- 3112039 TI - The use of a combined prescription kardex/pass medication sheet in long-stay hospitals. PMID- 3112041 TI - A proposal for a generally applicable de minimis dose. AB - This paper presents a proposal for a generally applicable de minimis radiation dose for members of the general public. A de minimis dose defines a level below which control of radiation exposures would be deliberately and specifically curtailed. Thus, such a dose must be set well below established limits on acceptable dose from all sources of exposure and, furthermore, must be below any established dose limit for specific practices. The proposed de minimis level consists of two dose limits: a principal limit on annual committed effective dose equivalent averaged over a lifetime of 0.01 mSv (1 mrem) and a subsidiary limit on committed effective dose equivalent in any year of 0.05 mSv (5 mrem). The proposed values are 1% of the limits on acceptable dose from all sources currently recommended by the International Commission on Radiological Protection (ICRP85), and correspond to a lifetime risk from continuous exposure of about 10( 5). PMID- 3112040 TI - [Peroral long-term treatment of psoriasis using fumaric acid derivatives]. AB - Oral treatment of psoriasis on an outpatient basis, using a preparation containing fumaric acid derivatives, was evaluated as initial monotherapy (3 months) and as long-term basic therapy (12-14 months) in 13 and 11 patients, respectively. The course of the disease was analysed in each individual case. After completion of both parts of the trial, half of the patients that had only responded poorly to conventional antipsoriatic therapy showed a significant improvement which occurred after several weeks of treatment. In 4 patients the medication had to be stopped because of abdominal pain. No severe side effects, particularly of a renal, hepatic or haematological nature, could be established. Studies in mice and rats disclosed only a low acute toxicity of the fumaric acid derivatives used. In additional analyses, hypotheses were dealt with concerning the mechanism of action of fumaric acid in psoriasis. To establish fumaric acid derivatives in the treatment of psoriasis, studies on chronic toxicity and pharmacokinetics will have to be conducted. Further clinical trials should evaluate a single fumaric acid derivative instead of mixtures. PMID- 3112042 TI - The volume-outcome relationship: practice-makes-perfect or selective-referral patterns? AB - Various studies have demonstrated that hospitals with larger numbers of patients with a specific diagnosis or procedure have lower mortality rates. In some instances, these results have been interpreted to mean that physicians and hospital personnel with more of these patients develop greater skills and that this results in better outcomes--the "practice-makes-perfect" hypothesis. An alternative explanation is that physicians and hospitals with better outcomes attract more patients--the "selective-referral pattern" hypothesis. Using data for 17 categories of patients from a sample of over 900 hospitals, we examine the patterns of selected variables with respect to hospital volume. To explore the plausibility of each hypothesis, a simultaneous-equation model is also used to test the relative importance of the two explanations for each diagnosis or procedure. The results suggest that both explanations are valid, and that the relative importance of the practice or referral explanation varies by diagnosis or procedure, in ways consistent with clinical aspects of the various patient categories. PMID- 3112046 TI - Argyria: report of a case associated with abnormal electroencephalographic and brain scan findings. PMID- 3112045 TI - Salmonella sepsis in ulcerative colitis: report of a case and review of the literature. PMID- 3112043 TI - Immunohistochemical localization of fibronectin in the human placentas at their different stages of maturation. AB - The distribution of fibronectin in the human placenta was studied by the aid of the immunoperoxidase technique using specific antibodies against it. In the early chorionic tissue, fibronectin was distributed along the trophoblastic basement membrane, on the wall of fetal blood vessels, in the connective tissue core, and in the cytotrophoblastic cell columns. In the term placenta, this glycoprotein was detected mainly on the fetal blood vessels and less intensely in the stroma, but not along the trophoblastic basement membrane. Endothelial cells of the blood vessels, fibroblastic cells in the stroma, and unidentified cells in the cytotrophoblastic cell columns were immunostained positively for fibronectin. These data suggest that fibronectin of the placenta is produced locally and retained in the tissue, if not all. PMID- 3112044 TI - Cross reactive identification of types 1 and 2C fibers in human skeletal muscles with monoclonal anti-neurofilament (200 kd) antibody. AB - Types 1 and 2C fibers in human skeletal muscle were cross-reactively identified with monoclonal anti-bovine neurofilament (200 kd) antibody. Thirty seven biopsy samples including sixteen vastus lateralis muscles, twelve lumbar paravertebral muscles, six gluteus medius muscles, two flexor carpi ulnaris muscles, and one flexor pollicis longus muscle, were examined. Serial transverse sections were stained histochemically with myofibrillar ATPase (pH 10.4, 4.6, 4.3) and DPNH tetrazolium reductase reactions, and immunochemically using the avidin-biotin peroxidase complex with the primary antibodies of monoclonal anti-bovine neurofilament (200 kd, 160 kd, 70 kd) antibodies and anti-bovine glial filament acidic protein antibody. The immunochemical reaction with anti-NF (200 kd) antibody could distinguish two kinds of fibers; positive and negative in all of the specimens. No fiber was recognized with other antibodies. Myosin ATPase reactions in serial sections proved that the positively stained fibers with anti NF (200 kd) antibody were types 1 and 2C fibers and negative fibers types 2A and 2B fibers. At present, it is not known what substance is responsible for the cross-reaction with the monoclonal anti-NF (200 kd) antibody in types 1 and 2C fibers, but this unique antibody would be valuable in two aspects: one concerns the problem of the evolution of fiber types, and the other the utility as another supplemental method to conventional myosin ATPase scheme. PMID- 3112047 TI - The treatment of advanced stage ovarian carcinoma with a combination of chemotherapy, radiotherapy, and radiosensitizer: report of a pilot study from the National Cancer Institute. AB - Twenty-eight patients with Stage III or IV ovarian carcinoma were treated with combined chemotherapy-radiotherapy employing a unique protocol. Four cycles of cyclophosphamide and hexamethylmelamine alternated with four cycles of concurrent cisplatin, whole abdominal radiotherapy, and intraperitoneal misonidazole. The entire treatment program lasted six months. Clinical complete responses were seen in 50% of the patients with an overall response rate of 61%. Pathologic complete response (PCR) confirmed at second look surgery occurred in 18% of the group (5 patients). Median survival of the entire group was 15.2 months with all PCR's alive NED. This outcome was no different than our previous experience with combination chemotherapy alone. Toxicities seen included leukopenia, thrombocytopenia, nausea, vomiting, and weight loss. However, these side effects were manageable. Two non-tumor deaths occurred. This study demonstrates the feasibility of combining drug and radiation therapy concurrently in the treatment of ovarian cancer; further research is needed to explore different sequencing and dose levels that could improve the outcome. PMID- 3112048 TI - Skene's gland abscess with suburethral diverticulum in an adolescent. AB - Suburethral diverticula have been reported to occur in 3-5% of adult females. They are rarely found in adolescents. We describe such a lesion that arose secondary to an abscess of Skene's glands in a 14-year-old sexually active adolescent. PMID- 3112049 TI - Cutaneous mast cell neoplasia in cats: 14 cases (1975-1985). AB - Cutaneous mast cell neoplasia was diagnosed in 14 cats from January 1975 to September 1985. Review of the available medical records and client communication provided information on tumor description, location, and recurrence, and each cat's current status. Twenty-three cutaneous mast cell neoplasms were surgically excised, examined, and graded histologically. In this study, feline cutaneous mast cell tumors did not metastasize to lymph nodes or viscera, did not recur at a previous excision site, and did not cause or contribute to the death of any cat. A histologic grading system described for canine mast cell tumors apparently provided no prognostic information for the cats in this study. There was a predilection for older male cats to develop cutaneous mast cell tumors, especially on the head and neck. PMID- 3112050 TI - Sarcoptes scabiei infestation in a cat. AB - Sarcoptes scabiei infestation was diagnosed in a cat. Clinical signs included thick, crusty, exudative dermatitis on the feet, caudal aspect of the thighs, and tail. Paronychia and dystrophic nails also were observed. The course of the disease was chronic. Concomitant and potentially predisposing additional health problems were suspected, but were not confirmed. PMID- 3112051 TI - Multiple hereditary ocular anomalies in a herd of cattle. AB - A Brahman x Santa Gertrudis herd of cows bred to a Hereford bull was evaluated because of a 3-year history of several calves born with congenital blindness. Multiple congenital ocular anomalies in 2 calves included microphthalmos, microcornea, microcoria, heterochromia iridis, microlentia, cataracts, retinal dysplasia, retinal detachment, anterior segment dysgenesis, acorea, and proliferation of the anterior neuroectoderm. On the basis of the lack of environmental factors and persistence of an intermittent problem when breeding to a single bull, a genetic defect was diagnosed as the probable cause. Dominant inheritance with varied expressivity may have best explained the lack of obvious signs in the bull, with emergence of various anterior and posterior segment defects in offspring from unrelated cows. PMID- 3112052 TI - Encephalitis caused by a Sarcocystis-like organism in a steer. AB - Sarcocystis spp can cause poor growth, anorexia, fever, anemia, muscular weakness, nervousness, abortion, and even death in cattle. Lesions in the CNS of cattle infected with Sarcocystis spp are microscopic and relatively minor, compared with those in other organs. We report extensive encephalitis in a steer attributable to a Sarcocystis-like organism. PMID- 3112054 TI - Inductions of ornithine decarboxylase and DNA synthesis in rat stomach mucosa by 1-nitrosoindole-3-acetonitrile. AB - Administration of 1-nitrosoindole-3-acetonitrile (NIAN) at doses of 40 to 300 mg/kg body weight by gastric intubation to male F344 rats induced up to 100-fold increase in ornithine decarboxylase activity with a maximum after 24 hr and up to 10-fold increase in DNA synthesis with a maximum after 16 hr in the pyloric mucosa of the stomach. These results suggest that NIAN has potential tumor promoting activity in carcinogenesis in the glandular stomach. PMID- 3112053 TI - AIDS studies in Japan. PMID- 3112055 TI - Cancer patterns among Koreans in Japan, Koreans in Korea and Japanese in Japan in relation to life style factors. AB - Cancer incidences for major sites were compared among Koreans in Osaka, Japan, Koreans in Korea and Japanese in Osaka by calculating standardized proportional incidence ratios (SPIR's), in addition to updating the findings on cancer mortality experiences of Koreans and Japanese in Osaka reported before. Compared with Japanese, Koreans in Osaka had significantly higher mortality rates from cancers of the esophagus, liver and lung in males, and liver in females. Mortality rates among Koreans in Osaka were significantly lower for stomach cancer in both sexes and for breast cancer in females. Compared with Korean counterparts in the homeland, Koreans in Osaka had a reduced risk for cancers of the stomach in males and the uterus in females. On the other hand, an elevated risk was observed for cancers of the esophagus, colon, liver and lung among Korean males in Osaka and for cancers of the colon and liver among Korean females in Osaka. The risk for cancer of the breast in females was similar among Koreans in the host and home countries. These different cancer patterns among Koreans in the host and home countries and Japanese are discussed in relation to their life styles, such as smoking, drinking and dietary habits, which have been investigated by means of questionnaire surveys. PMID- 3112056 TI - Breast self-examination practice and clinical stage of breast cancer. AB - The relationship between breast self-examination (BSE) and pre-treatment clinical stage of breast cancer was assessed in female breast cancer patients consisting of 30 patients practicing BSE monthly, 60 patients practicing occasionally, and 60 patients who had rarely or never practiced BSE. These patients were matched by age, residence, and hospital. More frequent practice of BSE was associated with more favorable clinical stage. The percentage of stage I patients was 33% for monthly performers, and this was significantly higher than the value of 14% for those who had rarely or never practiced. BSE practice was significantly related to tumor size measured before treatment in a dose-response manner. The average values of maximum tumor diameter were 2.5 cm for monthly performers, 3.0 cm for occasional performers, and 3.5 cm for those who had rarely or never practiced. The results suggest that BSE practice increases the probability of detecting smaller cancers at an early stage, and this may lead to a more favorable prognosis. PMID- 3112057 TI - Per capita foods/nutrients intake and mortality from gastrointestinal cancers in Japan. AB - Analytical epidemiologic studies are less effective when dietary habits are homogenous within a population. For that reason, we performed chronological and spatial correlation analyses between mortality from stomach and large intestinal cancers and various foods/nutrients intakes. The age-adjusted death rates (AADRs) for male colon cancer were strongly associated with the population size and those for female colon cancer and male rectal cancer were weakly associated with the population size, but the AADRs for stomach cancer in both sexes and those for female rectal cancer were not associated. From 1969-71 to 1981-83, the AADRs for stomach and female rectal cancers decreased and the AADRs for colon and male rectal cancers increased. With an increasing population size and from the earlier period to the recent period, the intakes of western-style fat-rich foods such as butter & margarine, cheese and ham & sausage increased and those of rice, fish and some traditional Japanese foods decreased. The results of geographical correlation analyses were generally consistent with the results from the urban rural variations. The chronological correlation analyses suggested that stomach cancer might be associated with Japanese-style dietary habits after almost no lag time and colon cancer might be associated with westernized dietary habits after a lag time of about 10 years. PMID- 3112058 TI - Intestinal metaplasia of the stomach in Swedish and Japanese patients without ulcers or carcinoma. AB - A systematic analysis of the cellular components of intestinal metaplasia (i.e., goblet cells with or without brush border cells and Paneth cells) was performed in endoscopic gastric biopsies from 984 patients without gastric ulcer or carcinoma; 359 Swedish and 625 Japanese patients. The Japanese patients, matched for age and sex, had twice as much intestinal metaplasia as the Swedes. The frequency of goblet cells and columnar cells with brush (absorptive) border increased with increasing age in both ethnic groups. Complete intestinal metaplasia (i.e. the presence of at least two or all three cellular components) was twice as frequent in the Japanese. This may reflect differences in the environment (including food habits) of the gastric mucosa in the two populations. Structural mucosal changes (i.e. pseudo-villus formations) were found more than twice as often in the Japanese. Since pseudo-villus changes occurred as often as goblet cells and brush border cells in both groups, it is suggested that the above-mentioned mucosal structural change should be considered for inclusion among the histological criteria of intestinal metaplasia of the stomach. Incomplete intestinal metaplasia (i.e. the occurrence of goblet cells without the other cellular components) occurred in similar proportions in the two populations. The present findings support the theory that incomplete intestinal metaplasia may be a para- rather than a preneoplastic phenomenon. PMID- 3112059 TI - Soft agar colony formation of bladder cells during carcinogenesis induced by N butyl-N-(4-hydroxybutyl)nitrosamine and application to detection of bladder cancer promoters. AB - N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was given to male Fischer 344 rats at a dose of 0.05% in drinking water for 2, 4, 6 and 12 weeks, and double soft agar colony formation of the uroepithelial cells was determined periodically, during and after this administration. In the group administered BBN for 2 weeks, no significant colony growth was observed until week 8. In the group given BBN for 4 weeks, colony growth was observed at week 4 and the numbers of colonies remained constant until week 8. In the group given BBN for 6 weeks, significant colony growth was observed at weeks 6 and 8. In the group on BBN for 12 weeks, colonies grew from week 4 and significant numbers of colonies were observed from week 6, increasing up to week 10. Colony formation preceded papilloma development in the rat bladder, and was dependent on the duration of BBN administration. The effect of amino acids and sodium saccharin on colony formation was also evaluated. The rats were given 0.05% BBN for 3 weeks, followed immediately by the administration for 9 weeks of 2% L-tryptophan, 1% D-tryptophan, 2% L-leucine, 2% D-leucine, 2% DL-leucine, 2% L-isoleucine, 2% DL-isoleucine or 5% sodium saccharin in the diet. At week 12, the numbers of colonies were significantly higher in the groups given sodium saccharin, L-leucine, DL-leucine, L-isoleucine, DL-isoleucine and D tryptophan. This method provides a potentially useful approach toward analyzing the early events in bladder carcinogenesis and may be applicable to detect new bladder carcinogens and promoters. PMID- 3112060 TI - Higher susceptibility to N-methyl-N'-nitro-N-nitrosoguanidine-induced tumorigenesis in an interstrain hybrid of the fish, Oryzias latipes (medaka). AB - Adult fish of an interstrain hybrid (F1) of inbred medaka, obtained from crosses between HO4C and HB32C, were exposed for 2 hr to an aqueous solution of the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine at concentrations of 15, 20, 25, 30, and 35 ppm. Survival and neoplastic changes were examined over a 6-month period. A large variety of neoplasms were induced, including melanoma, papilloma, ovarian tumors, olfactory epithelioma, branchioblastoma and fibroma. More than 60% of the tumors were classified as melanoma on the basis of histological examinations. A markedly higher cumulative incidence of the melanoma with a dose related response was demonstrated in the F1 hybrid fish compared to the parental strains. The latent period for melanoma development, however, remained unchanged in F1 compared to the parents. The variety of tumors induced in the F1 fish was greater than in the parental strains. The results indicate the usefulness of F1 hybrid fish in testing the carcinogenicity of certain water-soluble chemicals, due to their high sensitivity. PMID- 3112061 TI - H-2-controlled genetic susceptibility to pulmonary adenomas induced by urethane and 4-nitroquinoline 1-oxide in A/Wy congenic strains. AB - The genetic effect of the H-2 complex on the development of chemically induced pulmonary adenomas was clearly demonstrated in H-2 congenic strains with an A/Wy background which had a high susceptibility to pulmonary adenoma. A single subcutaneous injection of either urethane or 4-nitroquinoline 1-oxide was given to nine strains of mice. Among them, the number of adenoma foci per mouse was significantly higher in A/Wy (haplotype H-2a), A/J (H-2a), A.TL (H-2tl) and A.AL (H-2al) than in A.BY (H-2b), A.SW (H-2s), A.CA (H-2f) and A.TH (H-2t2) strains. In addition, the average number of adenoma foci in A/Wy (H-2a) was more than 20 times that in the B10.A (H-2a) strain. Thus, multiplicity of adenoma foci appeared to be regulated by at least two genes, one of which is located in the I or S region in the H-2 complex and the other in the non-H-2 genetic background. The genes in the H-2 complex were distinct from Pas-1 locus, which is probably identical to ptr. PMID- 3112062 TI - Differentiation by a tumor promoter of lymphoblastoid cell lines with and without Ph1 chromosome from a chronic myelogenous leukemia patient. AB - An attempt was made, by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), to induce differentiation in Ph1-positive (PB-1049) and Ph1-negative (LN 1049) B lymphoblastoid cell lines established from a patient with chronic myelogenous leukemia, and a Ph1-positive line (PB-1049-T) derived from a tumor nodule formed by inoculation of PB-1049 cells into nude mice. The changes induced by TPA in all lines were consistent with differentiation towards plasma cells, and included enhanced clustering of floating cells, reduced DNA synthesis, increase of the cytoplasm/nucleus ratio and appearance of a large amount of rough endoplasmic reticulum in the cytoplasm. Immunoglobulin concentration was estimated by ELISA in the supernatant of the three cell lines. Remarkable increases were observed in PB-1049 and PB-1049-T cultures treated with TPA. These results suggest that the Ph1-positive as well as Ph1-negative B lymphoblastoid cell lines examined have the potential to perform the proper functions of B lymphocytes in vitro. PMID- 3112063 TI - Immunochemically detected nuclear envelope-associated cytochrome P-450 component(s) in rat hepatocyte culture lines. AB - The presence and location of cytochrome P-450 in Donryu rat hepatocyte culture lines, Ac2F cells and 3 other cell lines were assessed by indirect immunofluorescence examination using anti-cytochrome P-450 monoclonal antibodies. Ac2F cells and other hepatocyte cell lines were selectively stained at their nuclear envelope, but not the cytoplasm, with a monoclonal antibody selective to a high-spin form of cytochrome P-448 (P-448H), although this monoclonal antibody stained primary cultured normal rat hepatocytes at both cellular components and did not stain hepatoma cells of 2 transplantation lines. The results of unscheduled DNA synthesis assay with Ac2F cells using several carcinogenic aromatic amines (4-aminoazobenzene derivatives and amino acid pyrolysis products) suggested that this nuclear envelope-associated cytochrome P-450 activates a restricted portion of these aromatic amines, i.e., a tryptophan pyrolysis component and a glutamic acid pyrolysis component. These results indicate that rat hepatocyte culture lines lack (or contain a reduced amount of) the cytoplasmic cytochrome P-450 but maintain a characteristic type of cytochrome P 450, probably a kind of cytochrome P-448H in their nuclear envelope, and this may be involved in oxidative metabolism of a restricted portion of aromatic amines. PMID- 3112064 TI - Therapeutic effect of cell-wall skeleton of Propionibacterium acnes in combination with a monoclonal antibody (C6-1.2) on the lung metastases of Lewis lung carcinoma. AB - The purpose of this study was to determine whether the combination of C6-1.2 monoclonal antibody (MoAb) (established in our laboratory), which is specifically reactive with Lewis lung carcinoma (3LL), and cell-wall skeleton of Propionibacterium acnes C7 (P. acnes-CWS) would significantly decrease established spontaneous metastases of 3LL. C6-1.2 MoAb combined with intratumoral (or intralesional) injection of P. acnes-CWS, when administered at an early stage of the experiment, showed a significant reduction of lung metastases in 3LL bearing mice. The treatment modality of C6-1.2 MoAb alone did not decrease the lung tumor colonies. On the other hand, the combined treatment of intravenous injection of P. acnes-CWS and C6-1.2 MoAb did not significantly reduce the lung metastases of 3LL tumors in 3LL-bearing mice compared with the treatment of P. acnes-CWS alone. In contrast, when the primary tumor was surgically removed, the most remarkable reduction of lung metastases was observed by the combination of intravenous administration of both C6-1.2 MoAb and P. acnes-CWS. We concluded that the antimetastatic activity of C6-1.2 MoAb and P. acnes-CWS varies depending on the injection route, and also that surgical excision of the primary tumor can lead to remarkable reduction of 3LL lung metastases. PMID- 3112065 TI - Effects of naloxone on human ovarian cancer cell growth in vitro and in vivo. AB - The effects of naloxone on human ovarian cancer cell growth in vitro and in vivo were examined by using an established cell line, designated KF, derived from human ovarian carcinoma. When the KF cells were incubated in the presence of various concentrations of naloxone for 72 hr, the cell proliferation was inhibited in a dose-dependent manner in the concentration range of 30 to 120 microM naloxone. The growth-inhibitory effect of naloxone could not be detected by 51Cr-release assay or colony-forming assay. The inhibition of cell proliferation by naloxone resulted from the inhibitory effect on protein synthesis in the KF cells, as confirmed by a marked decrease of incorporation of [3H]valine. In order to determine the effect of naloxone on tumor growth in vivo, ip injections 3 times a week of 2.5 or 5.0 mg/kg naloxone were initiated either one week prior to tumor inoculation (pretreated groups) or one week after tumor inoculation (post-treated groups). Nude mice in the pretreated groups had significantly smaller tumor volumes than those in the untreated group as long as naloxone was administered. On the other hand, in the post-treated groups a significant growth retardation was observed 2 weeks after initiation of treatment with 2.5 mg/kg naloxone. In comparison to a median survival time of 38 days for untreated controls, the naloxone pre- and post-treated groups showed increases of 26-71% in median survival. PMID- 3112066 TI - My personal impressions at the National Cancer Center Research Institute during my 4 months' stay as a fellow of the Foundation for Promotion of Cancer Research, 1986. PMID- 3112067 TI - Promoting effect of 12-O-tetradecanoylphorbol-13-acetate on neurogenic microtumors initiated by transplacental exposure to N-ethyl-N-nitrosourea. AB - The promoting effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the occurrence of neurogenic microtumors in SD-JCL rats initiated transplacentally with N-ethyl-N-nitrosourea (ENU) was investigated. The treatment with TPA induced earlier occurrence of microtumors than as compared with the initiation alone. Thus, TPA has tumor-promoting activity on the formation of neurogenic microtumors in rats prenatally exposed to ENU. PMID- 3112069 TI - Relationships of age, period, and birth cohort for stomach cancer mortality in Japan. AB - The mortality data on stomach cancer in Japan during 1955 to 1980 were analyzed by the use of an age-period-cohort model. Although the model could not give a unique solution of age, period, and cohort parameters, several sets of estimates of the parameters clarified particular features of each effect. Within a plausible range, the features were as follows. The period parameter underwent linear change from 1965 to 1980 for males and from 1970 to 1980 for females. The cohort parameters decreased birth cohort by birth cohort, at least among those who were born after 1891. The curve of the age parameter in females showed a shoulder around age 40 and a subsequent upward slope to age 80, while that in males was unimodal. The curve in females was compatible with the idea that there might be two different main entities in stomach cancer. The model also gave estimates of future trends in stomach cancer mortality under the assumption that there would be no additional change in period effect other than that expected from the recent quinquennia. The number of deaths from stomach cancer in males would be rather stable until 2000, and that in females would decline slightly. The age-adjusted and crude mortality rates would continue to decrease at least until 2000. PMID- 3112068 TI - Estimation of the number of cancer survivors according to site in Japan. AB - Based on incidence and survival data from the Osaka Cancer Registry, the numbers of cancer survivors were estimated by site in this study. The method used for estimation of survivors from all sites of cancer in the previous study was simplified further by not subdividing the data according to age-group. The observation period was the 25 years from 1960 to 1984. The number of incident cancers at all sites that occurred during the 25 years was estimated as 4,776,100. The leading sites of incidence during this 25-year period were the stomach (1,612,000), lung (427,100), and liver (329,100) for both sexes. The number of total cancer survivors on January 1, 1985 was estimated as 1,009,100. Among males, stomach cancer survivors accounted for 45% (180,100) of all survivors. The next most common sites were the rectum (7%, 27,000) and colon (6%, 25,600). Among females, the leading sites were the uterus (26%, 157,600), breast (22%, 132,100) and stomach (18%, 106,800). Most of the cancer survivors living at not more than 5 years after diagnosis were assumed to be receiving some kind of cancer medical care and were therefore regarded as an approximation of what is generally called "cancer prevalence." The number in this category for all sites was estimated as 417,900. The sites showing the largest numbers of these short term survivors were again the stomach, followed by the rectum and colon among males, and the breast, uterus, and stomach among females. The reliability and utility of the results are discussed. The results are compared with other recently reported registry data from other countries and with other estimated data in Japan. PMID- 3112070 TI - Incidence of squamous metaplasia in large bronchi of Japanese lungs: relation to pulmonary carcinomas of various subtypes. AB - The incidence of bronchial squamous metaplasia in Japanese lungs was investigated in order to clarify the significance of this lesion for the development of lung cancer of various histological subtypes. The bronchi of 104 and 32 lungs resected, respectively, for primary or metastatic tumors were step-sectioned and examined histologically. The incidence of squamous metaplasia was particularly high (83% of cases, 8-11% of sections) in male lungs bearing primary squamous or small cell carcinoma whereas it was low (43% of cases, 3% of sections) in lungs of both sexes with adenocarcinoma, the latter figures being about the same as those for lungs with secondary metastatic tumors. Although the overall incidence of lung squamous metaplasia in Japanese is much lower than in the U.S., the present data demonstrate a high level in association with squamous or small cell carcinoma, directly comparable to that of Americans. However, atypical metaplasia, or dysplasia, was encountered much less frequently than in the U.S. A topographical study of 7 minute or small squamous cell carcinomas revealed 3 to have adjacent and 2 to have nearby areas of squamous metaplasia. However, 2 cases were found to be completely free of squamous metaplastic lesion. Thus, squamous metaplasia may be associated with the development of squamous cell carcinoma but would appear not to be an obligatory step in the development of this neoplasm. PMID- 3112071 TI - Initiating, promoting and carcinogenic activities of three naphthofurans in a mouse skin long-term study. AB - The initiating, promoting and carcinogenic activities of three naphthofurans, 2 nitro-7-methoxynaphto[2,1-b]furan (A), 2-nitronaphtho[2,1-b]furan (C) and 7 methoxynaphtho[2,1-b]-furan (E), were determined in a long-term assay using CD1 mice, by means of a two-step skin painting regimen. Compound A was a strong initiator and a weak carcinogen, and compound C was a strong promotor and a moderate carcinogen, whereas compound E did not have any effect. The NO2 group at the 2 position on the molecule was concluded to be responsible for the carcinogenic activity of the former two naphthofurans. The addition of a CH3O group at position 7 enhanced the initiating ability while it diminished the promoting and carcinogenic potentials. These findings indicate that the initiating activity is closely linked to the mutagenic potential previously detected in in vitro and in vivo mammalian cell systems, while the promoting and carcinogenic activities are related to the effects detected in mouse short-term skin tests. PMID- 3112072 TI - Enhancing effect of cysteamine hydrochloride on the development of gastroduodenal tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine in F344 rats. AB - The effect of the duodenal ulceration induced by cysteamine hydrochloride on the development of gastroduodenal tumors initiated by N-methyl-N'-nitro-N nitrosoguanidine (MNNG) was studied in F344 rats of both sexes. Cysteamine (200 mg/kg body wt.) was administered by gastric intubation at various times, before, during or after a 16 week period of MNNG (100 mg/liter in drinking water) treatment. In the preliminary experiment, while the ulcers induced were confined to the proximal duodenum, the pyloric region of the stomach also showed slight erosion. Five of 25 male rats given cysteamine 2 weeks before the start of MNNG treatment developed adenocarcinoma in the duodenum as compared to 1 case in the MNNG alone group. In addition, animals of both sexes which received cysteamine during MNNG treatment yielded significantly increased incidences of adenocarcinoma in the pyloric area of the stomach. In line with earlier reports, the present findings suggest that mucosal damage and subsequent regeneration or proliferation of mucosa are important co-factors for MNNG-induced gastroduodenal carcinogenesis in rats. PMID- 3112073 TI - Synthetic analogues (indolactams) of (-)-indolactam-V are new congeners of the teleocidin class of tumor promoters. AB - (-)-Indolactam-V, which has the partial structure of teleocidins A and B, and has tumor-promoting activity, is a good model for use in studies on the relation between structure and tumor-promoting activity, whereas (+)-indolactam-V has no tumor-promoting activity. In this work, five racemic indolactams differing only in their alkyl group at C-12 of (-)-indolactam-V were synthesized and tested for biological and biochemical activities related to tumor promotion. The activities tested were inductions of ornithine decarboxylase in mouse skin and human promyelocytic leukemia (HL-60) cell adhesion, inhibition of specific [3H]12-O tetradecanoyl-phorbol-13-acetate binding to a mouse particulate fraction and activation of protein kinase C in vitro. The results showed that (+/-)-indolactam L and (+/-)-indolactam-F had almost the same activities as (+/-)-indolactam-V, suggesting that (-)-indolactam-L and (-)-indolactam-F are new tumor promoters with as high potency as (-)-indolactam-V. (+/-)-Indolactam-t-L, which has a highly lipophilic group at C-12 of (-)-indolactam-V, showed the highest activities in the above tests. (-)-Indolactam-t-L might have stronger tumor promoting activity than (-)-indolactam-V. Furthermore, the results with (-) indolactam-t-L indicated the possibility of designing new tumor promoters with stronger activity than teleocidin. PMID- 3112074 TI - Suppression of human immunodeficiency virus replication by 3'-azido-3' deoxythymidine in various human hematopoietic cell lines in vitro: augmentation of the effect by lentinan. AB - The effect of 3'-azido-3'-deoxythymidine (AZT) on replication of human immunodeficiency virus (HIV) in various hematopoietic cell lines was investigated. The concentration of AZT required to block HIV replication varied depending on the cell line used. U-937 cells required as little as 0.01 microM AZT to block HIV replication, a concentration almost 100 times lower than that required for MT-4 or MOLT-4 cells. However, 467 and TALL-1 cells required concentrations of AZT higher than 5 microM. It was clear that AZT was ineffective once the viral gene was integrated into chromosomal DNA; removal of AZT from culture fluids at that stage allowed the full expression of HIV. The effect of the potent immunostimulator lentinan was also examined, and it was shown that lentinan enhanced the effect of AZT. PMID- 3112075 TI - Anemia-inducing substance (AIS) in advanced cancer: inhibitory effect of AIS on the function of erythrocytes and immunocompetent cells. AB - The effects of anemia-inducing substance (AIS), found in the plasma of tumor bearing subjects, on red blood cells (RBC) and cellular immunity were examined. The results obtained may be summarized as follows: 1) The osmotic resistance and the deformability of RBC were decreased in patients with terminal cancer. 2) Normal human RBC were made less deformable and their membrane was made fragile by treatment with cachectic plasma from those patients, and these changes in physical properties were irreversible. 3) Energy metabolism in RBC was affected by AIS, that is, ATP concentration and pyruvate kinase activity in RBC were lowered and transmembrane glucose influx was suppressed. 4) AIS was removed from cachectic plasma by repeated adsorption with normal RBC, and the inhibitory effect on cellular immunity was lessened as AIS was removed. 5) AIS was detected in cachectic RBC membrane, monocytes, and tumor tissue by indirect immunofluorescence assay using rabbit anti-AIS antibody prepared by us. These observations suggest strongly that tumor-derived AIS appears in the blood of patients with terminal cancer, shows cytotoxicity to RBC and immunologically competent cells, and plays a role in the pathogenesis of cancer cachexy. PMID- 3112076 TI - Occurrence of tumor-associated ganglioside antigens with Hanganutziu-Deicher antigenic activity on human melanomas. AB - The specificity of antibody to NeuGc alpha 2-3Gal beta 1-4Glc-cer (GM3(NeuGc] was carefully reexamined by the method of enzyme-immunostaining on a thin layer plate. The affinity-purified antibody was found to react with NeuGc alpha 2 8NeuGc alpha 2-3Gal beta 1-4Glc-cer (GD3(NeuGc-NeuGc] and NeuGc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc-cer (GD3(NeuGc-NeuAc], but not with NeuAc alpha 2-8NeuGc alpha 2-3Gal beta 1-4Glc-cer (GD3(NeuAc-NeuGc)) or NeuAc alpha 2-8NeuAc alpha 2 3Gal beta 1-4Glc-cer (GD3(NeuAc-NeuAc]. From this result together with the previous results, it (GD3(NeuAc-NeuAc], From this result together with the previous results, it could be concluded that the antibody recognizes the outer portion of molecular species of sialic acids in the gangliosides. By using this antibody, the expression of Hanganutziu-Deicher (HD) gangliosides could be demonstrated in human malignant melanoma. The molecular species were different among individuals examined. Among HD-antigenic gangliosides, GM3(NeuGc) was commonly found in melanoma tissues. One of the patients examined expressed GD3(NeuGc-NeuGc) and GD 3(NeuGc-NeuAc), which may be characteristic gangliosides in human melanomas, since these gangliosides could not be detected in human colon cancer or human fetal tissues. PMID- 3112077 TI - Wide distribution of rat hepatoma asialo GM1 and its different responses to anti asialo GM1 antibody-mediated in vitro and in situ cell killing. AB - By means of TLC immunostaining with anti-asialo GM1 antiserum and conventional structural analyses including exoglycosidase treatment, permethylation and negative ion FABMS, asialo GM1 was found to be widely distributed in rat ascites hepatomas, AH130, AH109A, AH44, AH272, AH41C, AH60C, AH414, AH7974, AH66, AH66 alpha F, AH66F and AH13, and Yoshida sarcoma cells. However, reactivity of asialo GM1, when measured by flow cytometry and complement-mediated cytotoxicity assay with anti-asialo GM1 antiserum, was only observed on AH13 and AH66F, and did not necessarily correspond to the concentration of asialo GM1 on the cells, indicating a cryptic or unreactive nature of glycosphingolipids with respect to their antibodies. On the other hand, although rats injected with 10(7) cells of AH66F died within 7 days, treatment of the rats with anti-asialo GM1 antiserum was found to be effective for their cure or for prolonging their survival, indicating an in situ cytotoxic effect of antiserum. For the in situ cytotoxicity, the timing and period of injection and the dose of antiserum were found to be important. PMID- 3112078 TI - Obituary: Prof. Hamao Umezawa, M.D., Ph.D. (1914-1986). PMID- 3112079 TI - A new antitumor antibiotic, FR-900482. IV. Hematological toxicity in mice. AB - The new antibiotic FR-900482 (4-formyl-6,9-dihydroxy-14-oxa-1,11-diazatetracyclo [7.4.1.02,7. O10,12]tetradeca-2,4,6-triene-8-ylmethyl carbamate) possesses an antitumor activity equal to or greater than that of mitomycin C (MMC). The hematotoxicity of equivalent effective doses of the two compounds was compared in mice. A single iv injection of either compound similarly decreased the number of white blood cells (WBC) in the peripheral blood, whereas FR-900482 had no effect on the number of platelets (PTL). Both drugs slightly reduced the number of red blood cells (RBC). The effect of FR-900482 on the bone marrow cells (BMC) measured by cfu in spleen and cfu in culture was weaker than that of MMC. The results suggest that FR-900482 is a promising antitumor agent both in efficacy and safety. PMID- 3112080 TI - Production and biological activity of rebeccamycin, a novel antitumor agent. AB - An actinomycete, strain C-38,383, was selected in a screening program for the isolation of novel antitumor agents. A yellow crystalline product, named rebeccamycin, was isolated from the mycelium and was found to have activity against P388 leukemia, L1210 leukemia and B16 melanoma implanted in mice. Rebeccamycin inhibits the growth of human lung adenocarcinoma cells (A549) and produces single-strand breaks in the DNA of these cells. No DNA-protein cross links were detected. A related antibiotic, staurosporine, is produced by Streptomyces staurosporeus and Streptomyces actuosus. Strain C-38,383 was found to resemble closely strains of Nocardia aerocolonigenes recently renamed Saccharothrix aerocolonigenes. A strain selection isolate without aerial mycelium, C-38,383-RK-1, failed to produce rebeccamycin while a strain with aerial mycelium, C-38,383-RK-2, was found to be a suitable strain for production. A description of the producing strain is presented and its taxonomic position is reviewed. A fermentor containing 37 liters of production medium gave a rebeccamycin yield of 663 mg/liter after 204 hours of incubation with strain C 38,383-RK-2. PMID- 3112081 TI - Structure of fredericamycin A, an antitumor antibiotic of a novel skeletal type; spectroscopic and mass spectral characterization. AB - IR, UV-visible spectroscopy, circular dichroism, 1H and 13C NMR studies, high resolution electron impact, field desorption, and fast atom bombardment mass spectral studies are reported for fredericamycin A (NSC-305263), a novel antitumor antibiotic of acid-base indicator type produced by Streptomyces griseus (FCRC-48). The spectral data are correlated with the structure obtained by X-ray crystallography as (E,E)-6',7'-dihydro-4,9,9'-trihydroxy-6-methoxy-3'-(1,3 pentadienyl++ +)-spiro- [2H-benz[f]indene-2,8'-[8H]-cyclopent-[g]-isoquinoline] 1,1', 3,5,8(2'H)-pentone. The novel spiro ring antibiotic exhibits unusual 1H and 13C NMR spectroscopic and chemical behavior, not previously observed in other antibiotic structures. PMID- 3112082 TI - Neplanocin A inhibition of S-adenosylhomocysteine hydrolase in Alcaligenes faecalis has no effect on growth of the microorganism. AB - Neplanocin A, a cyclopentenyl analog of adenosine, is a naturally occurring antibiotic possessing potent inhibitory activity toward the enzyme S adenosylhomocysteine (AdoHcy) hydrolase. In the present study, we examined whether there was a correlation between the inhibition of prokaryotic AdoHcy hydrolase and the reported antibacterial activity of neplanocin A, e.g. Alcaligenes faecalis (Yaginuma et al., J. Antibiotics 34: 359 approximately 366, 1981). Of 16 bacterial species screened, only 2 organisms (both of which contained AdoHcy hydrolase) were sensitive to 10 nM neplanocin A when grown on agar plates. None of the 16 strains showed any growth sensitivity in broth culture to concentrations of the antibiotic as high as 4 mM. However, treatment of A. faecalis in broth culture with 14 microM neplanocin A resulted in complete inhibition of cellular AdoHcy hydrolase and subsequent elevation of intracellular AdoHcy. No alternative method for degrading or removing the excess AdoHcy from these cells was detected. Bacillus subtilis, which exhibited no AdoHcy hydrolase activity showed no alteration of AdoHcy metabolism when treated with the same concentration of the antibiotic. These results indicate that inhibition of AdoHcy hydrolase is not related to the antibacterial activity of neplanocin A and suggest that using this enzyme as a target for the design of antimicrobial agents is not likely to prove a productive approach. PMID- 3112084 TI - Influence of picolinic acid on the uptake of 65zinc-amino acid complexes by the everted rat gut. AB - Three hundred fifty rats were used in three experiments to: 1) validate the everted gut procedure as an in vitro technique for estimating Zn absorption, 2) determine the effect of increasing ratios of picolinic acid (PA) to Zn on Zn absorption and 3) determine the effect of PA on absorption of Zn and amino acid complexes at pH 6, 7 and 8. In the first experiment the time delay between tissue collection with subsequent storage in ice-cold saline and start of tissue incubation was 0, 10, 20 or 30 min. A linear decrease was observed for 65Zn uptake with increasing delay time. Lysine absorption was not affected by delay time. In the second experiment, molar ratios of PA:Zn of 0, .5, 1.0, 1.5, 2.0 and 2.5 with Zn held constant were evaluated. A linear decrease in 65Zn absorption from 65ZnCl2 occurred as the molar ratio of PA to Zn increased. In the third experiment, 0 and 5 molar ratios of PA to a constant Zn level were evaluated using 65ZnCl2, 65Zn-14C-methionine (ZnMet) and 65Zn-3H-lysine (ZnLys) at pH 6, 7 and 8. The addition of PA decreased Zn absorption regardless of Zn source. The data suggest that the Zn sources used were of similar biological value. The data do not support the theory that PA facilitates Zn absorption. PMID- 3112083 TI - Antibacterial activity of L-2-amino-4-chloro-4-pentenoic acid isolated from Amanita pseudoporphyria Hongo. PMID- 3112085 TI - Effect of excess levels of methionine, tryptophan, arginine, lysine or threonine on growth and dietary choice in the pig. AB - Six experiments were conducted with newly weaned pigs (8 kg) to evaluate the effects of 4% excesses of DL-methionine, L-tryptophan, L-threonine, L-lysine or L arginine on growth or "choice" (i.e., self-selection) when added to 20% protein, corn-soybean meal (C-SBM) diets. Arginine was supplied as the free base and lysine as lysine acetate to avoid acid-base problems. In the growth study, gain was reduced 52, 31, 28, 16 and 5% by additions of methionine, arginine, tryptophan, lysine and threonine, respectively. Small decreases in gain/feed occurred in pigs fed diets with excess methionine or lysine. Feed intake depressions were evident in pigs fed excess methionine or excess tryptophan within 1 d after initiation of the growth trial. Self-selection studies revealed that pigs strongly preferred the control diet over any of the diets containing excess amino acids. Further studies indicated that pigs preferred diets with excess threonine, lysine or arginine over those containing an equal excess (i.e., 4%) of methionine or tryptophan. Moreover, there was a tendency for pigs to prefer the diet with excess threonine over the one containing excess lysine or arginine. Also, pigs clearly preferred the diet with excess methionine over the diet containing excess tryptophan. When given a choice between a protein-free diet and a C-SBM diet containing 4% excess tryptophan, pigs initially (d 0 to 4) preferred the protein-free diet, but later adapted to the extent that during the last 4 d of the 12-d trial they consumed more of the tryptophan-imbalanced diet than of the protein-free diet. PMID- 3112086 TI - Postpartum interval in beef cows shortened by enclomiphene. AB - This study was designed to determine whether an anti-estrogen can block the negative effect of estrogens on luteinizing hormone (LH) release and therefore decrease the postpartum interval in suckled beef cows. In Exp. I, eight suckled postpartum beef cows were randomly assigned to treatment and control groups. Treatment cows received 1 g/d clomiphene citrate (im) from d 21 to 28 postpartum, while control cows were injected with saline. On d 28 postpartum, there was no difference (P greater than .05) in mean total and basal LH concentrations or LH pulse frequency between treatment and control cows. All control cows exhibited estrus on d 52 +/- 3; treatment cows exhibited estrus on d 134 +/- 12 (P less than .05). In Exp. II, 17 suckled cows were randomly assigned to three treatment groups: 1) control group (n = 6) receiving one empty implant, 2) 10-cm enclomiphene implant group (n = 5) and 3) 30-cm enclomiphene implant group (n = 6). The silastic implants were placed sc on d 20 and removed on d 29 postpartum. Mean total LH concentrations during d 24 to 29 postpartum in the 30-cm enclomiphene implant group were higher than the 10-cm implant (P less than .05) and control group (P less than .05). The postpartum period in the 30-cm enclomiphene group (45 +/- 6 d) was shorter than the 10-cm implant (94 +/- 24 d) and control (96 +/- 20 d) groups (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112087 TI - Comparison of most probable number and pour plate procedures for isolation and enumeration of sulphite-reducing Clostridium spores and group D faecal streptococci from oysters. AB - A comparative study of methods to enumerate sulphite-reducing Clostridium spores and Group D faecal streptococci in oysters demonstrated that pour plate solid agar techniques gave higher counts than liquid broth most probable number procedures. Reinforced clostridial broth with supplements to detect sulphite reduction was compared with pour plates of egg yolk-free tryptose sulphite cycloserine agar incubated at 37 degrees C for 24 h. Azide dextrose broth was compared with pour plates using Slanetz and Bartley (SB) agar or KF-streptococcus agar at 37 degrees C. Most probable number procedures used for both groups of organisms gave excessive numbers of improbable tube combinations. For enumeration of Group D faecal streptococci, a pour plate technique using SB agar incubated at 37 degrees C for 48 h is recommended. PMID- 3112088 TI - Characterization and DNA homology of Lactobacillus strains isolated from pig intestine. AB - Twenty strains of the genus Lactobacillus were isolated from pig intestines and characterized with phenotypic tests. Eleven of these strains, together with selected reference strains, were subjected to DNA homology studies. Three major groups could be distinguished by biochemical/physiological tests and by DNA homology studies: one homofermentative group of the subgenus Thermobacterium and two heterofermentative groups. The DNA homology studies revealed that strains from the homofermentative group were related to Lactobacillus acidophilus strain VPI 1754, but showed a low relationship to the type strain of Lact. acidophilus. One One group of the heterofermentative strains was related to the type strain of Lact. reuteri; the other group, consisting of three strains, showed a low relationship to all reference strains used. These three strains had the unusual property of producing succinic acid in large amounts. PMID- 3112089 TI - The effect of ampicillin and tylosin on the faecal enterococci of healthy young chickens. AB - Enterococcal isolates from young chickens were differentiated into one of three species, namely Enterococcus faecalis, Ent. faecium and Ent. gallinarum. The proportion of each species among the enterococcal population changed with time in birds not dosed with antibiotics. This pattern of change was modified in birds dosed with either tylosin or ampicillin even though ampicillin did not select for ampicillin resistance among the enterococcal population. A gradual increase in tylosin resistance was recorded with time among the enterococci of the 'undosed' control birds. This was associated with an increase in the proportion of Ent. faecium, a species commonly resistant to tylosin, among the enterococci of the birds as they grew older. PMID- 3112090 TI - Expanding the impact of behavioral staff management: a large-scale, long-term application in schools serving severely handicapped students. AB - Experimental evaluations of behavioral staff management procedures usually have been limited to relatively small-scale demonstration studies. We evaluated a large-scale, long-term application of a staff management program designed to improve the functional utility of educational services for severely handicapped persons. The intervention, involving a brief in-service program followed by supervisory prompts and feedback, was implemented by three principals in four schools involving 21 classrooms. Implementation of the management procedures was consistently accompanied by increases in student involvement in functional educational tasks in each classroom. Further, the improved services continued throughout a 2-year follow-up period. Staff responses to a questionnaire indicated a high degree of staff acceptance of the management program. Results are discussed in terms of expanding the use of behavioral supervisory procedures from experimental demonstrations to actual adoption by existing human service agencies. PMID- 3112091 TI - The effect of sublethal concentrations of aminoglycosides on adherence of Pseudomonas aeruginosa to hamster tracheal epithelium. AB - Perfused hamster tracheal explants were used to examine the adherence of mucoid and non-mucoid strains of Pseudomonas aeruginosa to intact tracheal epithelium when grown in 0.5 MIC of tobramycin or gentamicin. Tracheal explants were perfused for 2 h with 10(7) cfu of P. aeruginosa grown overnight in trypticase soy broth containing 0.5 MIC of tobramycin or gentamicin or without antibiotics. After infection, the explants were washed and a 4 mm section was homogenized, diluted and plated for colony counts. Mucoid strains of P. aeruginosa grown in the presence of the aminoglycosides did not produce alginate and were not as adherent as the same strains which were not grown in antibiotics. Adherence of non-mucoid strains of P. aeruginosa grown in sublethal concentrations of the aminoglycosides was not significantly reduced compared with the adherence of the same strains which were not exposed to antibiotics. These results indicate that mucoid strains of P. aeruginosa growing in the presence of sublethal concentrations of aminoglycosides do not produce alginate and may not colonize the epithelial surface. PMID- 3112092 TI - The effect of sublethal levels of antibiotics on the pathogenicity of Pseudomonas aeruginosa for tracheal tissue. AB - Hamster tracheal organ cultures were used to evaluate the ability of two aminoglycoside and two beta-lactam antibiotics to protect the epithelium from damage due to Pseudomonas aeruginosa infection. Hamster tracheal explants were infected with strains of P. aeruginosa for 4 h and washed to remove nonadherent organisms. The explants were incubated for an additional 18 h in fresh minimal essential medium containing inhibitory or subinhibitory concentrations of antibiotics. The explants were examined by scanning electron microscopy and bacterial elastase and exotoxin A production was detected by ELISA and a western blot assay respectively. Concentrations of aminoglycosides below the MIC for the infecting strain protected the epithelium from damage and inhibited the production of exotoxin and elastase. The beta-lactam antibiotics were not protective and epithelial damage was observed at antibiotic levels equal to or higher than the MIC for that strain. The beta-lactam treated cultures continued to release elastase and exotoxin A at antibiotic concentrations equivalent to or higher than the MIC for that strain. Thus subinhibitory levels of aminoglycoside antibiotics could protect the infected epithelium from damage by inhibiting the release of toxic substances from the invading bacteria. In contrast, bacteria exposed to beta-lactam antibiotics may continue to release extracellular toxins which can damage the tissue. PMID- 3112093 TI - In-vitro susceptibility of oral streptococci to pristinamycin. AB - The inhibitory activity of pristinamycin against oral streptococci was compared with that of amoxycillin, erythromycin and vancomycin. Minimum inhibitory concentrations (MICs) of pristinamycin ranged from 0.03-1 mg/l (mode 0.25 mg/l), similar to those for amoxycillin. Erythromycin had a mode MIC of 0.06 mg/l and vancomycin, the least active, 1 mg/l. However, in killing curve experiments to compare the bactericidal activities of pristinamycin and erythromycin against several strains of oral streptococci, pristinamycin was substantially more active, consistently producing a rapid decrease in viable count during the first few hours of incubation. Pristinamycin may prove to be of value for the prophylaxis of post-dental extraction bacteraemia. PMID- 3112094 TI - Comparative in-vitro activity of five fluoroquinolones against mycobacteria. AB - Fifty distinct strains of mycobacteria were investigated to determine their in vitro susceptibility to five new fluoroquinolones (norfloxacin, pefloxacin, ofloxacin, enoxacin and ciprofloxacin). Ofloxacin and ciprofloxacin were found to be the most active, with minimum inhibitory concentrations (MIC) of 1.25 mg/l or less to all strains of Mycobacterium tuberculosis, M. bovis, M. xenopi, M. kansasii and BCG tested. All agents showed little activity against M. malmoense and M. avium-intracellulare complex with MIC values of greater than 2.5 mg/l. PMID- 3112095 TI - In-vitro activity of six fluorinated quinolones against Mycobacterium tuberculosis. AB - Thirty-five clinical isolates of Mycobacterium tuberculosis, 24 susceptible and 11 resistant to conventional primary antituberculous drugs, were tested against six new quinolones. The mode MICs of isoniazid susceptible organisms on 7H11 agar for ciprofloxacin, ofloxacin, enoxacin, norfloxacin, CI-934 and A56620 were 1.0, 1.0, 2.0, 2.0, 1.0 and 1.0 mg/l, respectively. Strains resistant to isoniazid and other antituberculous agents were usually inhibited within one dilution of these values. These new quinolones could serve as alternate therapeutic agents or they may accelerate the antimycobacterial effects of conventional chemotherapy; these hypotheses should now be tested in experimental infections. PMID- 3112096 TI - Activity of ciprofloxacin against Mycobacteria in vitro: comparison of BACTEC and macrobroth dilution methods. AB - Various clinical isolates of mycobacteria were tested for susceptibility to ciprofloxacin by a standard macrobroth dilution test and the radiometric BACTEC method. Agreement between the two test systems was species dependent: Mycobacterium tuberculosis (80%), M. kansasii with M. scrofulaceum (30%), M. avium-intracellulare (20%), and 0% for the rapidly growing mycobacteria. Most mycobacterial strains other than M. tuberculosis were susceptible to the breakpoint ciprofloxacin concentration of 2 mg/l as determined by BACTEC MICs, whereas none were susceptible by macrobroth testing. Seven of nine M. tuberculosis isolates were susceptible by either method. Ciprofloxacin merits further study as a potential antimycobacterial agent. PMID- 3112097 TI - Resistance of Pseudomonas aeruginosa to imipenem is independent of beta-lactamase production. PMID- 3112098 TI - Survey of resistance of Pseudomonas aeruginosa to aminoglycosides and beta-lactam antibiotics in the Netherlands. PMID- 3112099 TI - Radiolabelling of penicillin-binding proteins (PBPs) in intact Pseudomonas aeruginosa cells: consequences of beta-lactamase activity by PBP-5. AB - The time-course of labelling of penicillin-binding proteins (PBPs) was compared for intact and sonicated cell preparations of nine Pseudomonas aeruginosa strains, all of which gave identical PBP profiles. Saturation of all the PBPs in cell-sonicates occurred within 2 min of exposure to 35 mg/l 14[C] benzylpenicillin. PBP-5 formed an unstable penicilloyl-complex: the other PBPs formed highly stable complexes. Saturation of PBP-4 in intact cells occurred within 2 min of exposure to the antibiotic, correlating with the high affinity of this protein for penicillin. Labelling of PBPs 1a, 1b and 3 was slow but progressive, suggesting that these proteins were shielded by the permeability barrier(s) of the cell. Labelling of PBP-5 in intact cells achieved 10-20% saturation within 2-10 min of exposure to 35 mg/l 14[C] benzylpenicillin, but did not increase subsequently. This behaviour may indicate the establishment of a steady state between the formation and breakdown of the PBP-5-penicillin complex, suggesting that PBP-5, potentiated by the permeability barrier, functions as a feeble beta-lactamase. Such activity may distort the labelling of other PBPs by reducing the concentration of penicillin in the periplasm, thus invalidating the PBP accessibility experiments that have been recommended as probes of bacterial permeability. The beta-lactamase activity also may be significant in resistance, since Noguchi et al. (Journal of Antibiotics, 1980, 33, 1521-6) have previously associated the loss of PBP-5-beta-lactamase activity with hypersusceptibility to beta-lactams in P. aeruginosa. PMID- 3112100 TI - The activity of the 4 quinolone Ro 23 6240 and the cephalosporins Ro 15 8074 and Ro 19 5247 against penicillin sensitive and resistant gonococci. AB - We have compared the in-vitro activity of the 4-quinolone Ro 23 6240 and the oral cephalosporins Ro 15 8074 and Ro 19 5247 with that of penicillin, spectinomycin, cefuroxime, ceftriaxone, ciprofloxacin, ofloxacin and norfloxacin against 60 strains of Neisseria gonorrhoeae. MICs 90 against penicillinase producing N. gonorrhoeae (PPNG) and chromosomally-mediated resistant N. gonorrhoeae (CMRNG) respectively were: spectinomycin 16 and 16 mg/l, cefuroxime 0.12 and 1.0 mg/l, ceftriaxone 0.008 and 0.03 mg/l, Ro 15 8074 0.015 and 0.12 mg/l, Ro 19 5247 0.015 and 0.12 mg/l, Ro 23 6240 0.06 and 0.06 mg/l, ciprofloxacin 0.008 and 0.015 mg/l, ofloxacin 0.03 and 0.06 mg/l, norfloxacin 0.06 and 0.12 mg/l. The spectinomycin resistant and spectinomycin-sensitive strains did not differ. All three new agents show good activity against gonococci and warrant further clinical investigation. Ro 23 6240 in common with the other 4-quinolones appears to be as active against gonococcal strains exhibiting non-enzymic chromosomal resistance to penicillin as against PPNG and penicillin-sensitive isolates. PMID- 3112101 TI - Effects of tissue-type plasminogen activator on Staphylococcus epidermidis- infected plasma clots as a model of infected endocardial vegetations. AB - The ability of tissue-type plasminogen activator (t-PA) to enhance the effect of antibiotics in the treatment of bacterial endocarditis was studied using plasma clots infected with Staphylococcus epidermidis as a model of infected endocardial vegetations. A concentration-dependent lysis of the infected plasma clots was induced by t-PA, as shown by the decrease in the weight of the clots, a decrease in the amount of incorporated 125I fibrin, as well as the release of staphylococci from the clots into the incubation fluid. The addition of cloxacillin to the incubation medium in various concentrations led to a concentration-dependent decrease of the number of S. epidermidis in the clots. The presence of t-PA did not enhance the antibacterial effect of cloxacillin. It is concluded that the lysis induced by t-PA might enhance the effect of treatment of endocarditis by reducing the size of endocardial vegetations but not by enhancement of the effect of antibiotics on the bacteria embedded in the vegetations. PMID- 3112102 TI - Pseudomonas peritonitis in neutropenic rats treated with amikacin, ceftazidime and ticarcillin, alone and in combination. AB - Peritonitis in neutropenic rats, caused by a strain of Pseudomonas aeruginosa resistant to amikacin and ticarcillin alone but susceptible to ceftazidime and combinations of amikacin with ticarcillin, amikacin with ceftazidime and ticarcillin with ceftazidime, was investigated. Four hours after a bacterial challenge with a LD70 intraperitoneal dose of P. aeruginosa (1.5 X 10(8) cfu/ml), either amikacin, ticarcillin, ceftazidime, amikacin-ticarcillin, amikacin ceftazidime, or ticarcillin-ceftazidime was administered at dosing intervals that mimicked the serum concentrations of the drugs found in humans after therapeutic doses. When the serum concentrations did not exceed the MIC, as occurred with amikacin, no difference in survival was observed compared with controls. All other regimens resulted in animal survival during the treatment. When therapy was stopped only those regimens resulting in serum concentrations above the MBC were effective (amikacin-ticarcillin, amikacin-ceftazidime, ticarcillin-ceftazidime). The recovery of viable bacteria from the peritoneum agreed well with mortality. PMID- 3112103 TI - Interaction of rifampicin or rifapentine with other agents against Pseudomonas aeruginosa. PMID- 3112104 TI - Central vs. peripheral chemoreceptors in ventilatory stimulation by Hacetate. AB - Intravenous infusion of Hacetate in conscious rabbits induces a greater decrease in cerebrospinal fluid (CSF) [HCO3-] and arterial CO2 partial pressure (PaCO2) than does HCl, HNO3, or Hacetate. To test whether acetate per se can stimulate central chemoreceptors, HCl- or Hacetate-acidified mock CSF was infused via the cisterna magna in conscious rabbits with catheters preimplanted under anesthesia. HCl infusion induced a greater decrease in PaCO2 refuting this hypothesis. To evaluate the role of the carotid body HCl and Hacetate were infused intravenously in an intact (CB+) and a chemodenervated group (CB-). In CB+ rabbits Hacetate infusion produced a greater decrease in PaCO2. In CB- rabbits, the fractional decrease in arterial PaCO2 was less for both acids compared with that of the CB+ rabbits, but it was significantly greater for Hacetate infusion (21.2 +/- 2.5%, mean +/- SE) than for HCl infusion (14.5 +/- 1.8%). Thus the carotid body is not necessary for the greater Hacetate ventilatory stimulation. The working hypothesis is that nonionic diffusion of Hacetate into brain or acetate replacement of HCO3- in CSF production lowers [HCO3-] near central chemoreceptors. PMID- 3112105 TI - Effects of raised osmolarity on canine tracheal epithelial ion transport function. AB - Evaporation of water from upper airway surfaces increases surface liquid osmolarity. We studied the effects of raised osmolarity of the solution bathing the luminal surface of excised canine tracheal epithelium. Osmolarity was increased by adding NaCl or mannitol. NaCl addition induced a concentration dependent fall in short-circuit current and a rise in transepithelial conductance (-33% and +14% per 100 mosM, respectively). Unidirectional isotopic fluxes of 22Na, 36Cl, and [14C]mannitol were measured in short-circuited tissues in the base-line state and after addition of NaCl or mannitol to an isotonic mucosal solution. NaCl addition (75 mM) caused a 50% increase in conductance (G) and a parallel increase in [14C]mannitol permeability (Pmann), indicating an increase in paracellular permeability. Net Cl- secretion was reduced 50%, and net Na+ absorption was unchanged despite an increased chemical gradient for absorption, indicating an inhibition of active ion transport. Mannitol addition (150 mM) abolished net Na+ absorption but did not increase G or Pmann or change net Cl- secretion. These results suggest that responses to increased tracheal surface liquid osmolarity during spontaneous breathing may occur in both the cellular (inhibition of active Na+ and Cl- transport) and paracellular (increased [14C]mannitol permeability) compartments of the mucosa. PMID- 3112106 TI - Cardiorespiratory changes during HCl infusion unrelated to decreases in circulating blood pH. AB - To test the hypothesis that infusion of HCl changes blood pressure and respiration independent of decreases in circulating blood pH, an extracorporeal arteriovenous shunt (20 ml/min) between the femoral artery and vein was installed in anesthetized cats. Into this loop, acid (0.25 M HCl) and, approximately 10 cm downstream, base (0.25 M NaOH) could be infused simultaneously. Likewise, either acid or base could be infused individually. Right ventricular (Prv) and arterial (Pa) blood pressure, tidal volume (VT), and respiratory frequency (fresp) were recorded as well as blood gases and pH in arterial, right ventricular, and shunt loop blood at the reentrance into the animal. When HCl and NaOH were infused simultaneously and at equimolar rates (0.2 mmol/min for 10 min), there was a large increase in Prv, with little change or decrease in Pa. Respiratory frequency was increased, but total ventilation was not elevated because of a concomitant fall in VT. The rise in Prv and increase in fresp were transient in that they could only be evoked during the first HCl-NaOH infusion in a given animal. Repetitive infusions of HCl-NaOH into the same animal failed to elicit the response. Similar transient acid effects were evoked when HCl was infused without NaOH but not when NaOH was infused without HCl. During the second and third infusion of HCl, ventilatory responses were elicited that were explainable by stimulation of known chemoreceptors. The transient rise in Prv and fresp evoked by acid infusion might be explained by release of an agent from blood elements at the tip of the HCl infusion catheter, which in turn would constrict pulmonary vessels and influence breathing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112107 TI - Bacterial pneumonia stimulates macromolecule secretion and ion and water fluxes in sheep trachea. AB - In vivo instillation of Pasteurella haemolytica (greater than or equal to 10(7) colony-forming units/kg) into a lobar bronchus of sheep produced bacterial pneumonia by 7 days postinoculation. Infection was verified bacteriologically and histologically. Macromolecule secretion and ion and water fluxes were subsequently measured in tracheal tissues in vitro and were compared with values from sham-infected sheep. Macromolecules were radiolabeled with 35SO4 and [3H]threonine, and we measured the secretion of macromolecule-bound radiolabel onto the mucosa. Unidirectional fluxes of Cl-, Na+, and water were measured with radioactive tracers under open-circuit and short-circuit conditions. Lung infection increased basal secretion of bound 35SO4 (by 189%) and bound [3H] threonine (by 110%). It significantly increased net Na+ absorption under open- and short-circuit conditions and induced open-circuit net absorption of Cl- and water (16 +/- 29 microliters X cm-2 X h-1). These changes were associated with specific recruitment of neutrophils and elevated levels of arachidonate metabolites (thromboxane B2 and leukotriene B4) in the airways. Thus the bacterial pneumonia-induced changes in tracheal mucus secretion may be the result of airway inflammation. PMID- 3112108 TI - Ventilatory control in hypercapnia and exercise: optimization hypothesis. AB - A model of the respiratory control system incorporating both chemical and respiratory neuromechanical feedbacks is proposed to describe the steady-state ventilatory responses to CO2 inhalation and exercise. It is postulated that ventilatory output (VE) is set by the respiratory center to minimize a net operating cost representing the conflicting challenges of arterial chemical imbalance and respiratory-mechanical discomfort (intolerance of effort), given, respectively, by a quadratic function of arterial PCO2 and a logarithmic function of VE. In addition, the system is assumed to be mechanically limited at maximum VE (Vmax). The predicted responses in VE during moderate hypercapnia, exercise, and ventilatory loading closely mimic those normally observed, even though no separate signal unique to exercise is assumed. As a quantitative validation, the model yielded good fits to ventilatory response data obtained in eight healthy subjects during eucapnic and hypercapnic exercise; the predicted Vmax averaged approximately 77% of the maximum voluntary ventilation in all subjects. The results demonstrate the plausibility of the proposed optimization mechanism and suggest an important role for respiratory-mechanical factors in the control of VE. PMID- 3112109 TI - Contribution of continuing gas exchange to phase III exhaled PCO2 and PO2 profiles. AB - Changes in PCO2 and PO2 during expiration have been ascribed to simultaneous gas exchange, but other factors such as ventilation-perfusion inhomogeneity in combination with sequential emptying may also contribute. An experimental and model approach was used to study the relationship between gas exchange and changes in expired PCO2 and PO2 in anesthetized dogs during prolonged high tidal volume expirations. Changes in PCO2 and PO2 were quantified by taking the area bounded by the sloping exhalation curve and a line drawn horizontally from a point where the Fowler dead space plus 250 ml had been expired. This procedure is similar to using the slope of the exhalation curve but it circumvents problems caused by nonlinearity of the PCO2 and PO2 curves. The gas exchange components of the CO2 and O2 areas were calculated using a single-alveolus lung model whose input parameters were measured in connection with each prolonged expiration. The relationship between changes in experimental CO2 areas caused by sudden reductions in mixed venous PCO2 (produced by right atrial infusions of NaOH) and those calculated by the model was also studied. In seven dogs, calculated CO2 and O2 areas were 13% higher and 25% lower than the respective experimental areas, but interindividual variations were large. Changes in experimental CO2 areas caused by step changes in mixed venous PCO2 were almost identical to changes in the calculated areas. We conclude that the changes in PCO2 and PO2 during expiration cannot be explained solely by gas exchange. However, the single alveolus lung model accurately predicts changes in the CO2 exhalation curve caused by alterations in the alveolar CO2 flow. PMID- 3112110 TI - Regression analysis of use-dilution disinfectant test data as an alternative to current registration practices. AB - The historical application of probit analysis applied to the use-dilution disinfectant test is discussed. Attention is focused on earlier work which either deleted or incompletely applied confidence limits leading to much current controversy in disinfectant test interpretation. It is proposed that the probit analysis approach applied to disinfectants is indeed feasible and that a more complete application of confidence limits to the assay will yield more reliable data than those currently required for disinfectant product registration with the Environmental Protection Agency. A suggested modified registration protocol using probit analysis is offered as an alternative to the current registration guidelines. PMID- 3112111 TI - Coplanar polychlorinated biphenyls in aroclor and kanechlor mixtures. AB - Three congeners of coplanar PCBs (non-o-o'-chlorine-substituted polychlorinated biphenyls) were determined in representative commercial PCB preparations. The 3,3',4,4'-tetrachlorobiphenyl was highest in Kanechlor 400 (8500 micrograms/g) and Aroclor 1248 (6060 micrograms/g) followed by Kanechlors 300, 500, and 600 and Aroclors 1242, 1254, and 1260 in that order. The toxic 3,3',4,4',5 pentachlorobiphenyl and 3,3',4,4',5,5'-hexachlorobiphenyl were also detected in those mixtures. The highest concentrations of 3,3',4,4',5-pentachlorobiphenyl were found in Kanechlor 400 (89.3 micrograms/g) and Aroclor 1248 (62.3 micrograms/g) followed by Kanechlors 500, 300, and 600 and Aroclors 1254, 1242, and 1260 in that order. The 3,3',4,4',5,5'-hexachlorobiphenyl was detected in all Kanechlor mixtures, with the highest concentration (1.16 micrograms/g) in Kanechlor 500. However, among Aroclor mixtures, it was detected only in Aroclor 1254 at a concentration of 0.66 micrograms/g. The importance of these toxic constituents in PCB mixtures is worth considering in view of widespread pollution of the environment by PCBs. PMID- 3112112 TI - Determination of aflatoxin M1 in milk and milk products contaminated at low levels. AB - A new method is described for the determination of aflatoxin M1 in milk and dairy products by thin layer chromatography. The main characteristic is the extraction system using an alkaline solution. Lipids are removed by centrifuging at low temperatures, and the aflatoxins are then extracted with CHCl3. The method has 2 options: Technique II (detection limit 0.02 ppb) requires cleanup on a chromatographic column; this is not necessary in Technique I (detection limit 0.1 ppb). The recovery rate in both techniques is over 92.8% in milk and yoghurt. This method may also be used for other aflatoxins. Because of the advantages of the method, Technique II is recommended for aflatoxin M1 control in milk, where a low detection limit is necessary. Technique I is proposed for experimental aflatoxin production studies in dairy products, which require analysis of a large number of samples but which do not require a very low detection limit. PMID- 3112113 TI - Fluorimetric determination of aflatoxin M1 in cheese. AB - A simple and sensitive method is proposed for the determination of aflatoxin M1 in cheese. The ground cheese sample is extracted with acetone-water (3 + 1). Acetone is evaporated under vacuum, and the aqueous phase is passed through a C18 disposable cartridge. After the cartridge is washed with acetonitrile-water (1 + 9), the toxin is eluted with acetonitrile. The extract is then cleaned up on a silica cartridge. Final analysis is performed by 2-dimensional thin layer chromatography (TLC) combined with fluorodensitometry or by liquid chromatography on a reverse phase C18 column with fluorescence detection. Recovery is greater than 90%, and the coefficient of variation is 6% or less. The detection limit is in the range of 10 ng/kg. The identity of aflatoxin M1 is confirmed by formation of the M2a or acetyl-M1 derivative and rechromatography. PMID- 3112114 TI - Identification of mammalian feces by coprostanol thin layer chromatography: method development. AB - Existing methods for the identification of mammalian fecal particles in foods have not been completely satisfactory because visual identification of small particles is difficult. In addition, identification of feces by determining the presence of fecal alkaline phosphatase is limited to specimens in which the enzyme has not been inactivated, and it does not work well with feces from herbivores. A new method has been developed which uses coprostanol as a fecal indicator. Coprostanol is a heat-stable sterol found in the feces of mammals and some birds. A hexane extract of the suspect particle is applied to the preadsorbent zone of a silica gel thin layer chromatography plate which has been impregnated with 5% phosphomolybdic acid in ethanol. The plate is developed in diethyl ether-heptane (55 + 45), heated, and examined visually for the presence of coprostanol. Amounts of rat feces as small as 0.15 mg and cow feces as small as 0.5 mg have been identified using this method. PMID- 3112116 TI - Determination of ergotamine tartrate in tablets by liquid chromatography with fluorescence detection. AB - A method is presented for the liquid chromatographic (LC) determination of ergotamine tartrate in tablets that is applicable even in the presence of other ingredients such as phenobarbital, belladonna alkaloids, and caffeine. The sample is transferred to a volumetric flask, a small volume of formic acid is added to dissolve and stabilize the ergotamine, and the solution is diluted to volume with methanol. The solution is mixed and filtered through paper. The LC system consists of a Rheodyne injector fitted with a 20 microL loop and a C18 reverse phase column; the mobile phase is acetonitrile-water-triethylamine (700 + 300 + 0.5). Ergotamine tartrate is determined fluorometrically at an excitation wavelength of 250 nm and an emission wavelength of 430 nm. Recovery studies were conducted at the 0.3 and 1.0 mg levels. Average recoveries were 99.6 and 100.8%, respectively; relative standard deviations (RSDs) were 1.08 and 2.21%, respectively. Some commercial preparations containing ergotamine tartrate in combination with other ingredients were also analyzed. The RSDs for 5 determinations of each of 2 ground composites were 0.09 and 0.34%. PMID- 3112115 TI - Identification of mammalian feces by thin layer chromatography of coprostanol: collaborative study. AB - Mammalian feces contain coprostanol (5 beta-cholestan-3 beta-ol). In this study, 7 collaborators each tested 45 unknown specimens by a thin layer chromatographic method that uses coprostanol as an indicator of feces. The materials tested were 5 replicates each of 3 test portion sizes (0.5, 1.0, and 5.0 mg) of cockroach excreta (negative), and cow and rat feces (both positive). Of 315 specimens tested, 261 (82.9%) were correctly identified; there were 5 false positives, 26 false negatives, and from 1 collaborator, 23 inconclusive results. PMID- 3112117 TI - Acquired haemophilia. PMID- 3112118 TI - Association of Marfan's syndrome and epilepsy. PMID- 3112119 TI - Isolation and characterization of a new globomycin-resistant dnaE mutant of Escherichia coli. AB - We isolated a globomycin-resistant, temperature-sensitive mutant of Escherichia coli K-12 strain AB1157. The mutation mapped in dnaE, the structural gene for the alpha-subunit of DNA polymerase III. The in vivo processing of lipid-modified prolipoprotein was more resistant to globomycin in the mutant strain 307 than in its parent. The prolipoprotein signal peptidase activity was also increased twofold in the mutant, and there was a threefold increase in the activity of isoleucyl-tRNA synthetase. The results suggest that a mutation in dnaE may affect the expression of the ileS-lsp operon in E. coli. In addition, strain 307 showed a reduced level of streptomycin resistance compared with its parental strain AB1157 (rpsL31). Strain 307 was killed by streptomycin at a concentration of 200 micrograms/ml, which did not affect the rate of bulk protein synthesis in this mutant. A second mutation which was involved in the reduced streptomycin resistance in strain 307 was identified and found to be closely linked to or within the rpsD (ramA, ribosomal ambiguity) gene. Both dnaE and rpsD were required for the reduced streptomycin resistance in strain 307. PMID- 3112120 TI - Aerobactin utilization by Neisseria gonorrhoeae and cloning of a genomic DNA fragment that complements Escherichia coli fhuB mutations. AB - Aerobactin, a dihydroxamate siderophore produced by many strains of enteric bacteria, stimulated the growth of Neisseria gonorrhoeae FA19 and F62 in iron limiting medium. However, gonococci did not produce detectable amounts of aerobactin in the Escherichia coli LG1522 aerobactin bioassay. We probed gonococcal genomic DNA with the cloned E. coli aerobactin biosynthesis (iucABCD), aerobactin receptor (iutA), and hydroxamate utilization (fhuCDB) genes. Hybridization was detected with fhuB sequences but not with the other genes under conditions which will detect 70% or greater homology. Similar results were obtained with 21 additional strains of gonococci by colony filter hybridization. A library of DNA from N. gonorrhoeae FA19 was constructed in the phasmid vector lambda SE4, and a clone was isolated that complemented the fhuB mutation in derivatives of E. coli BU736 and BN3307. These results suggest that fhuB is a conserved gene and may play a fundamental role in iron acquisition by N. gonorrhoeae. PMID- 3112121 TI - Sodium-coupled motility in a swimming cyanobacterium. AB - The energetics of motility in Synechococcus strain WH8113 were studied to understand the unique nonflagellar swimming of this cyanobacterium. There was a specific sodium requirement for motility such that cells were immotile below 10 mM external sodium and cell speed increased with increasing sodium levels above 10 mM to a maximum of about 15 microns/s at 150 to 250 mM sodium. The sodium motive force increased similarly with increasing external sodium from -120 to 165 mV, but other energetic parameters including proton motive force, electrical potential, the proton diffusion gradient, and the sodium diffusion gradient did not show such a correlation. Over a range of external sodium concentrations, cell speed was greater in alkaline environments than in neutral or acidic environments. Monensin and carbonyl cyanide m-chlorophenylhydrazone inhibited motility and affected components of sodium motive force but did not affect ATP levels. Cells were motile when incubated with 3-(3,4-dichlorophenyl)-1,1 dimethylurea and arsenate, which decreased cellular ATP to about 2% of control values. The results of this investigation are consistent with the conclusion that the direct source of energy for Synechococcus motility is a sodium motive force and that below a threshold of about -100 mV, cells are immotile. PMID- 3112122 TI - Genetic studies of a secondary RNA polymerase sigma factor in Bacillus subtilis. AB - sigma B (sigma 37) is a secondary species of RNA polymerase sigma factor found in the gram-positive bacterium Bacillus subtilis. To study the function of sigma B genetically, we sought mutations that block the expression of a gene (ctc) known to be transcribed by sigma B-containing RNA polymerase in vitro. One such mutation, called crl, was found to map in or near the structural gene (sigB) for sigma B. To determine directly whether mutations in sigB would prevent transcription of ctc, we replaced sigB in the B. subtilis chromosome with insertion and deletion mutations that disrupted the sigma B coding sequence. Like crl, these in vitro-constructed mutations blocked expression of ctc, but had little or no effect on viability, sporulation, expression of the sporulation gene spoVG, or production of sporulation-associated alkaline protease. Using fusions of ctc to the reporter genes xylE and lacZ, we also identified mutations that enhanced ctc expression. One such mutation, called socB, was found to be located in an open reading frame immediately downstream of sigB. PMID- 3112123 TI - Secretion and processing of staphylococcal nuclease by Bacillus subtilis. AB - We have studied the secretion and processing of Staphylococcus aureus nuclease in Bacillus subtilis. We show that the initial species of nuclease found in the cell supernatants during short-term radioactive labeling (pulse-chase) had a molecular weight of approximately 18,800 and comigrated in a sodium dodecyl sulfate polyacrylamide gel with staphylococcal nuclease B. This nuclease B form was processed to the mature nuclease A extracellularly by a phenylmethylsulfonyl fluoride-sensitive protease. The nuclease B-processing site is a consensus signal peptidase site, and the processing of nuclease B was coupled to secretion as judged by pulse-chase experiments. The nuclease A was shown by microsequencing of the N terminus to be 2 amino acid residues shorter than the nuclease A described for S. aureus Foggi. The nuclease B form was still the first species found in the culture supernatant after removal of the N-terminal 26 amino acids of the native 60-amino-acid signal peptide. However, removal of the N-terminal 72 amino acids abolishes secretion of any nuclease form and leads to the intracellular accumulation of nuclease. PMID- 3112125 TI - Multiple catalases in Bacillus subtilis. AB - Vegetative cells of Bacillus subtilis in logarithmic growth phase produced one catalase, labeled catalase 1, with a nondenatured molecular weight of 205,000. As growth progressed, other activity bands with slower electrophoretic mobilities on polyacrylamide gels appeared, including a series of bands with a common nondenatured molecular weight of 261,000, collectively labeled catalase 2, and a minor band, with a molecular weight of 387,000, labeled catalase 3. Purified spores contained only catalase 2, and it was not produced in spo0A- or spo0F containing mutants. Strains deficient in catalase 1 or catalase 2 or both were selected after mutagenesis. Sensitivities of the two main catalases to NaCN, NaN3, hydroxylamine, and temperature were similar, but the apparent Kms for H2O2 differed, being 36.6 and 64.4 mM, respectively, for catalase 1 and catalase 2. The levels of catalase 1 increased 15-fold during growth into stationary phase and could be increased 30-fold by the addition of H2O2 to the medium. Catalase 2, which was not affected by H2O2, appeared only after the cells had reached stationary phase, and the maximum levels were only half of the basal level of catalase 1. PMID- 3112124 TI - Nucleotide sequence of the Rickettsia prowazekii citrate synthase gene. AB - The Rickettsia prowazekii citrate synthase (gltA) gene, previously cloned in Escherichia coli, was localized to a 2.0-kilobase chromosomal fragment. DNA sequence analysis of a portion of this fragment revealed an open reading frame of 1,308 base pairs that encodes a protein of 435 amino acids with a molecular weight of 49,171. This translation product is comparable in size to both the E. coli and pig heart citrate synthase monomers and to the protein synthesized in E. coli minicells containing the rickettsial gene. Comparisons between the deduced amino acid sequence of R. prowazekii citrate synthase and those of the E. coli and pig heart enzymes revealed extensive homology (59%) between the two bacterial proteins. In contrast, only 20% of the rickettsial enzyme residues were shared with the functionally similar pig heart enzyme residues. Upstream from the open reading frame and in close proximity to one another, sequences with homology to E. coli consensus sequences for RNA polymerase and ribosome binding were identified. S1 nuclease mapping experiments demonstrated that the start of transcription for this gene in E. coli was located in the upstream region. Codon usage in the rickettsial gltA gene was found to be very biased and differed from the pattern observed in E. coli. Adenine and uracil were used preferentially in the third base position of rickettsial codons. PMID- 3112126 TI - Metabolic initiation of differentiation and secondary metabolism by Streptomyces griseus: significance of the stringent response (ppGpp) and GTP content in relation to A factor. AB - I investigated the significance of the intracellular accumulation of guanosine 5' diphosphate 3'-diphosphate (ppGpp) and of the coordinated decrease in the GTP pool for initiating morphological and physiological differentiation of Streptomyces griseus, a streptomycin-producing strain. In solid cultures, aerial mycelium formation was severely suppressed by the presence of excess nutrients. However, decoyinine, a specific inhibitor of GMP synthetase, enabled the cells to develop aerial mycelia in the suppressed cultures at concentrations which only partially inhibited growth. A factor (2S-isocapryloyl-3S-hydroxymethyl-gamma butyrolactone) added exogenously had no such effect. Decoyinine was also effective in initiating the formation of submerged spores in liquid culture. The ability to produce streptomycin did not increase but decreased drastically on the addition of decoyinine. This sharp decrease in streptomycin production was accompanied by a decrease in intracellular accumulation of ppGpp. A relaxed (rel) mutant was found among 25 thiopeptin-resistant isolates which developed spontaneously. The rel mutant had a severely reduced ability to accumulate ppGpp during a nutritional shift-down and also during postexponential growth and showed a less extensive decrease in the GTP pool than that in the rel+ parental strain. The rel mutant failed to induce the enzymes amidinotransferase and streptomycin kinase, which are essential for the biosynthesis of streptomycin. The abilities to form aerial mycelia and submerged spores were still retained, but the amounts were less, and for both the onset of development was markedly delayed. The decreased ability to produced submerged spores was largely restored by the addition of decoyinine. This was accompanied by an extensive GTP pool decrease. The rel mutant produced A factor normally, indicating that synthesis of A factor is controlled neither by ppGpp nor by GTP. Conversely, a mutant defective in A factor synthesis accumulated as much ppGpp as did the parental strain. It was concluded that morphological differentiation of S. griseus results from a decrease in the pool of GTP, whereas physiological differentiation results from a more direct function of the rel gene product (ppGpp). It is also suggested that A factor may render the cell sensitive to receive and respond to the specified signal molecules, presumably ppGpp (for physiological differentiation) or GTP (for morphological differentiation). PMID- 3112127 TI - Different small, acid-soluble proteins of the alpha/beta type have interchangeable roles in the heat and UV radiation resistance of Bacillus subtilis spores. AB - Spores of Bacillus subtilis strains which carry deletion mutations in one gene (sspA) or two genes (sspA and sspB) which code for major alpha/beta-type small, acid-soluble spore proteins (SASP) are known to be much more sensitive to heat and UV radiation than wild-type spores. This heat- and UV-sensitive phenotype was cured completely or in part by introduction into these mutant strains of one or more copies of the sspA or sspB genes themselves; multiple copies of the B. subtilis sspD gene, which codes for a minor alpha/beta-type SASP; or multiple copies of the SASP-C gene, which codes for a major alpha/beta-type SASP of Bacillus megaterium. These findings suggest that alpha/beta-type SASP play interchangeable roles in the heat and UV radiation resistance of bacterial spores. PMID- 3112128 TI - Isolation of DNA encoding sucrase genes from Streptococcus salivarius and partial characterization of the enzymes expressed in Escherichia coli. AB - Restriction enzyme fragments containing two sucrase genes have been isolated from a cosmid library of Streptococcus salivarius DNA. The genes were expressed in Escherichia coli cells, and the properties of both enzymes were studied in partially purified protein extracts from E. coli. One gene encoding an invertase type sucrase was subcloned on a 2.4-kilobase-pair fragment. The sucrase enzyme had a Km for sucrose of 48 mM and a pH optimum of 6.5. The S. salivarius sucrase clone showed no detectable hybridization to a yeast invertase clone. Two overlapping subclones which had 1 kilobase pair of DNA in common were used to localize a fructosyltransferase gene. The fructosyltransferase had a Km of 93 mM and a pH optimum of 7.0. The product of the fructosyltransferase was a levan. A fructosyltransferase clone from Bacillus subtilis did not hybridize to S. salivarius DNA. The properties of the enzymes were compared with those of previously characterized sucrases. PMID- 3112130 TI - Decreased chromate uptake in Pseudomonas fluorescens carrying a chromate resistance plasmid. AB - CrO4(2-) resistance in Pseudomonas fluorescens LB300(pLHB1) was related to reduced uptake of CrO4(2-) relative to the plasmidless strain LB303. 51CrO4(2-) was transported mainly via the SO4(2-) active transport system; thus, cells grown with 0.15 mM cysteine, a repressor of the SO4(2-) transport system, were much more resistant to CrO4(2-) than those grown with 0.15 mM djenkolic acid, which derepressed the 35SrO4(2-) uptake system. Kinetics of 51CrO4(2-) uptake by P. fluorescens with and without the plasmid showed that the Vmax for 51CrO4(2-) uptake with the resistant strain was 2.2 times less than the Vmax for the sensitive strain, whereas the Km remained constant. PMID- 3112129 TI - Characterization and structure of genes for proteases A and B from Streptomyces griseus. AB - Protease A and protease B are extracellular proteins which are secreted by Streptomyces griseus. The genes encoding protease A (sprA) and protease B (sprB) were isolated from an S. griseus genomic library by using a synthetic oligonucleotide probe. Fragments containing sprA and sprB were characterized by hybridization and demonstration of proteolytic activity in Streptomyces lividans. Each DNA sequence contains a large open reading frame with the coding region of the mature protease situated at its carboxy terminus. The amino terminus of each reading frame appears to encode a 38-amino-acid signal peptide followed by a 76- or 78-amino-acid polypeptide, a propeptide, which is joined to the mature protease. Strong homology between the coding regions of the protease genes suggests that sprA and sprB originated by gene duplication. PMID- 3112131 TI - Guanine nucleotides stimulate arachidonic acid release by phospholipase A2 in saponin-permeabilized human platelets. AB - GTP or GTP gamma S alone caused low but significant liberation of arachidonic acid in saponin-permeabilized human platelets but not in intact platelets. GTP or GTP gamma S also enhanced thrombin-induced [3H]arachidonic acid release in permeabilized platelets. Inhibitors of the phospholipase C (neomycin)/diacylglycerol lipase (RHC 80267) pathway for arachidonate liberation did not reduce the [3H]arachidonic acid release. The loss of [3H]arachidonate radioactivity from phosphatidylcholine was almost equivalent to the increase in released [3H]arachidonic acid, suggesting the hydrolysis of phosphatidylcholine by phospholipase A2. The effect of GTP gamma S was greater at lower Ca2+ concentrations. These data indicate that the release of arachidonic acid by phospholipase A2 in saponin-treated platelets may be linked to a GTP-binding protein. PMID- 3112132 TI - Purification and properties of beta-D-glucosidase (linamarase) from the butter bean, Phaseolus lunatus. AB - A beta-D-glucosidase (linamarase) was purified 11,700-fold from the butter bean, Phaseolus lunatus L., by means of successive procedures including extraction, ammonium sulfate fractionation, acetone treatment, and chromatographies on CM Sephadex, DEAE-Sephadex, and Sephadex G-200. The final preparation gave a single protein band on both disc polyacrylamide gel electrophoresis and SDS polyacrylamide gel electrophoresis. In spite of its electrophoretic purity, the final enzyme preparation showed four glycosidase activities; beta-D-glucosidase, beta-D-galactosidase, beta-D-fucosidase, and beta-D-xylosidase. The molecular weight of the enzyme was determined to be 124,000 +/- 9,000 by Sephadex G-200 gel filtration, and 59,000 +/- 2,400 by SDS-disc gel electrophoresis. The enzyme showed a pH optimum in the range of 5.1 to 6.0 with p-nitrophenyl beta-D glucoside, 4-methylumbelliferyl beta-D-glucoside, and linamarin. Among natural substrates containing a beta-glucosyl terminal, linamarin, prunasin, and salicin were hydrolyzed by the enzyme from butter beans, but amygdalin, cellobiose, gentiobiose, and laminarin were hardly hydrolyzed. PMID- 3112133 TI - Time-dependent differential effects of natural and recombinant murine interferon gamma on ornithine decarboxylase activity of tumor cells. AB - Incubation of quiescent tumor cells with fetal calf serum induced ornithine decarboxylase (ODCase) activity concomitantly with mitogenic stimulation. Pretreatment of cells with highly purified natural or recombinant murine interferon-gamma (MuIFN-gamma) for 5 h caused a dose-dependent increase of ODCase activity induced by fetal calf serum (FCS). Pretreatment of target cells with IFN gamma for 5 h in absence of FCS stimulation did not induce ODCase activity. When pretreatment of cells with natural or recombinant MuIFN-gamma was prolonged for 18 h both ODCase activity and DNA synthesis induced by FCS were suppressed. By contrast when a mixture of MuIFN-alpha and -beta was used, ODCase activity was significantly suppressed after 5 h pretreatment compared to untreated controls. These results suggest that IFN-gamma exerts a differential effect on mitogen stimulated events depending on the dose and the time of addition. PMID- 3112134 TI - Effect of insulin on the glucose utilization in isolated cardiac myocytes from adult rat. AB - The acute effects of insulin on glucose utilization in isolated rat quiescent cardiac myocytes were studied. Insulin (80 nM) increased the rate of glucose clearance by 2-3 times in the presence of glucose ranging from 0.3 microM to 5.5 mM. Glucose transport, which was measured in terms of both D-glucose uptake in the presence of 0.3 microM D-glucose and initial rate of uptake of 3-O methylglucose, was stimulated 3-fold in the presence of insulin. At higher glucose concentrations (greater than 100 microM), a decrease in glucose clearance rate due to a shift of the rate-limiting step from glucose transport to a post transport step in the pathway of glucose metabolism was observed. At the physiological concentration of glucose (5.5 mM), about 73% of glucose was metabolized into lactate, about 10% was oxidized into CO2 and the rest (17%) remained inside the cells. The pentose phosphate pathway did not contribute to the glucose metabolism in these cells. Insulin (80 nM) significantly increased the uptake of glucose (112%), and the conversions of glucose into lactate (16%), glycogen (64%), and triglyceride (18%), but not into CO2 (3%). Insulin transiently increased the percentage of I-form of glycogen synthase by 16% above basal, but did not affect the percentage of a-form of glycogen phosphorylase. The content of glucose 6-phosphate in the cells was increased by 46% above the basal value in the presence of insulin. These results indicate that insulin has different acute stimulatory effects on various steps in the metabolic pathway of glucose in isolated quiescent cardiac myocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112135 TI - A single mutation prevents the normal intracellular transport of multiple lysosomal proteins from the rough endoplasmic reticulum. AB - Dictyostelium discoideum strain HMW-426 has been previously shown to be defective in the proteolytic processing of the lysosomal enzyme precursor to alpha mannosidase. We have now shown that the mutant is defective in the proteolytic processing of a second lysosomal enzyme, beta-glucosidase. Digestion of the HMW 426 alpha-mannosidase and beta-glucosidase precursors with endoglycosidase H revealed that the majority of oligosaccharide side chains on both precursors were sensitive to cleavage by this enzyme, indicating that both precursors fail to reach the Golgi apparatus. Subcellular fractionation experiments demonstrated that these two mutant precursors accumulated inside the lumen of the rough endoplasmic reticulum. The alpha-mannosidase precursor is conformationally altered, as evidenced by its abnormal protease susceptibility, suggesting that altered conformation is responsible for a generalized defect in transport of lysosomal protein precursors from the rough endoplasmic reticulum in the mutant. PMID- 3112136 TI - Primary structure of soybean lipoxygenase-1. AB - The primary structure of lipoxygenase-1 from soybeans has been determined. The results were deduced from the nucleotide sequence of the complete cDNA for isozyme lipoxygenase-1 and were confirmed by Edman sequencing of selected peptides obtained by CNBr cleavage and supported by carboxyl-terminal sequencing of the intact protein and by partial peptide analysis employing fast atom bombardment-mass spectroscopy. The enzyme has a molecular weight of 94,038 based on its content of 838 amino acids. PMID- 3112137 TI - Histone synthesis during the cell cycle of Physarum polycephalum. Synthesis of different histone species is not under a common regulatory control. AB - The synthesis of histones and nonhistone nuclear proteins was studied during the naturally synchronous cell cycle of Physarum polycephalum. Contrary to the commonly accepted idea of a tight coupling of histone biosynthesis and DNA replication during the somatic cell cycle we found that 40% of total histone synthesis takes place in the G2 period in the complete absence of DNA synthesis. The core histones exhibit a maximum of synthesis during S-phase. The synthesis of histones H2A and H2B continues during the G2 period, but synthesis of H4 and H3 is restricted to the S-phase of the cell cycle. Experiments with hydroxyurea demonstrated that the synthesis of H4 and H3 is completely dependent on unperturbed DNA synthesis, whereas synthesis of H2A and H2B is independent from DNA synthesis during the entire cell cycle. This implicates significant differences between the arginine-rich histones H4 and H3 and the moderately lysine-rich histones H2A and H2B with respect to the control mechanisms of their synthesis, the metabolic stability, and the function for chromatin structure. The nonhistone nuclear proteins are synthesized throughout the cell cycle with a broad maximum in the early G2 period. The cell cycle pattern of synthesis of H1 rather resembles the pattern of the nonhistone proteins than of core histones. PMID- 3112138 TI - Role of receptors in metabolic interaction of histamine with human vascular endothelial cells and skin fibroblasts. An ordered sequence of enzyme action. AB - The interaction of histamine with an H1 receptor on human endothelial cells evokes production of the lipid mediator prostaglandin I2 (PGI2) and is accompanied by tachyphylaxis of this H1 receptor response (Baenziger, N. L., Fogerty, F. J., Mertz, L. F., and Chernuta, L. F. (1981) Cell 24, 915-923). We have explored the affected cells' capability for subsequent metabolic degradation of histamine molecules. Human vascular endothelial cells and skin fibroblasts exhibit a two-stage histamine degradation sequence whose participants are an enzyme native to the cells themselves and one provided from an extracellular source. Initially, the cells' endogenous histamine N-methyltransferase activity mediates conversion of cell-associated [3H]histamine to tele-methylhistamine with retention of this intermediate metabolite. Subsequently, in the presence of exogenous diamine oxidase derived from fetal calf serum or human placenta, cell associated tele-methyl-histamine is further converted to the end product methylimidazoleacetic acid. After an initial lag phase lasting 3-6 min, the cell associated radioactivity accumulates as methylimidazoleacetic acid at a linear rate substantially enhanced over that without diamine oxidase. The entire sequence is blocked by the histamine methyltransferase inhibitor homodimaprit. Accumulation of [3H]histamine metabolites by endothelial cells is saturable both with respect to exogenous diamine oxidase and to histamine. Thus this metabolic pathway is carried out at the level of the individual cell by means of binding sites or receptors for the substrate and for the distal degradative enzyme, diamine oxidase. PMID- 3112139 TI - The effects of 6-diazo-5-oxo-L-norleucine, a glutamine analogue, on the structure of the major cartilage proteoglycan synthesized by cultured chondrocytes. AB - Incubation of embryonic chick chondrocytes with 6-diazo-5-oxo-L-norleucine (DON), a glutamine analogue, led to a dose-dependent inhibition of [35S]sulfate incorporation into proteoglycan. In the absence of exogenous L-glutamine, a maximal inhibition of 50-60% was achieved with DON concentrations greater than or equal to 1 microgram/ml (6 microM); the ED50 was approximately 0.2 microM. This inhibitory effect could be partially restored by the addition of 100-fold molar excess of either exogenous L-glutamine or M-glucosamine. The quantitative changes were due neither to inhibition of protein core synthesis nor to undersulfation of glycosaminoglycan chains. Rather, the proteoglycan synthesized in the presence of DON contained substantially fewer (approximately 50% of control) and smaller (10 15% of control, on the average) chondroitin sulfate chains as well as a paucity of keratan sulfate chains. The result of these structural changes was a proteoglycan with significantly lower molecular weight, buoyant density, and anionic charge. In spite of these modifications, the altered proteoglycan synthesized in the presence of DON was secreted normally and retained the ability to interact with exogenous hyaluronic acid and link proteins. The results of our experiments also indicate that DON substantially diminished the pool of hexosamine precursors required for glycosaminoglycan synthesis. We conclude that this decrease was responsible for the molecular alterations described above; and these, in turn, can account for the morphological changes previously seen in cartilage matrix synthesized in the presence of DON. PMID- 3112140 TI - Post-translational modifications of the core-specific lectin. Relationship to assembly, ligand binding, and secretion. AB - The rat core-specific lectin (CSL) or mannan-binding protein is synthesized and secreted by rat hepatocytes and H-4-II-E hepatoma cells. Prior to secretion proline and lysine residues with collagen-like sequences undergo hydroxylation and subsequent glycosylation of hydroxylysine to produce glucosylgalactosylhydroxylysine. Hydroxylation and subsequent glycosylation are inhibited by alpha,alpha'-dipyridyl (Colley, K. J., and Baenziger, U. U. (1987) J. Biol. Chem. 262, 10290-10295). We have used alpha,alpha'-dipyridyl to investigate the role of hydroxylation and glycosylation on interchain disulfide bond formation, assembly of subunits into high molecular weight complexes, attainment of carbohydrate and lipid binding ability, and secretion. Formation of disulfide-bonded dimers and trimers in the endoplasmic reticulum, assembly into high molecular weight complexes in the Golgi, and attainment of carbohydrate binding activity occur in either the presence or absence of these post translational modifications. The mature fully processed form of the CSL binds hydrophobic matrices and is secreted at a slow, but linear, rate. Inhibition of proline and lysine hydroxylation and hydroxylysine glycosylation prevents CSL secretion and attainment of binding activity for hydrophobic matrices. Secretion of the lectin, although slow, appears to be an active process and may be related to the capacity to interact with membranes and/or lipids. Other proteins known to contain collagen-like sequences such as acetylcholinesterase, pulmonary surfactant apoproteins, and C1q also interact with lipids and/or membranes. The collagen-like domains of these proteins may also play a role in promoting such interactions. PMID- 3112141 TI - Cell-mediated reduction of the interfragment disulfide in nicked diphtheria toxin. A new system to study toxin entry at low pH. AB - When 125I-labeled nicked diphtheria toxin bound to Vero cells was exposed to pH less than 5.0, a small fraction was reduced to yield A- and B-fragments. The pH required for reduction correlates well with that required to induce intoxication, and the amount of A-fragment released was of the same order as that required to intoxicate the cells. Conditions that protect cells against intoxication, such as acidification of the cytosol, treatment with anion transport inhibitors, or treatment with anti-diphtheria toxin antibodies, prevented the reduction of the interfragment disulfide in cell-bound toxin. In vitro, thioredoxin reduced nicked diphtheria toxin only at pH 5.0 and lower, and the reduction was inhibited by anti-toxin antibodies. This indicates that a conformational change in the toxin, necessary for reduction by the thioredoxin system, is prevented by the antibodies. Reduction by glutathione and cysteine was most efficient at neutral pH and was not inhibited by anti-toxin. The results are consistent with the possibility that cell-mediated reduction of the interfragment disulfide is a measure of the entry of fragment A into the cytosol. PMID- 3112142 TI - Novel phenylalanine dehydrogenases from Sporosarcina ureae and Bacillus sphaericus. Purification and characterization. AB - NAD+-dependent phenylalanine dehydrogenases were purified 1,500- and 1,600-fold, and crystallized from Sporosarcina ureae SCRC-R04 and Bacillus sphaericus SCRC R79a, respectively. The purified enzymes were homogeneous as judged by disc gel electrophoresis. The enzyme from S. ureae has a molecular weight of 305,000, while that of B. sphaericus has a molecular weight of 340,000. Each is probably composed of eight subunits identical in molecular weight. The S. ureae enzyme showed a high substrate specificity in the oxidative deamination reaction acting on L-phenylalanine, while that of B. sphaericus acted on L-phenylalanine and L tyrosine. The enzymes had lower substrate specificities in the reductive amination reaction acting on alpha-keto acids. The Sporosarcina enzyme acted on phenylpyruvate, alpha-ketocaproate, alpha-keto-gamma-methylthiobutyrate and rho hydroxyphenylpyruvate. The Bacillus enzyme acted on rho-hydroxyphenylpyruvate, phenylpyruvate, and alpha-keto-gamma-methylthiobutyrate. The enzyme from B. sphaericus catalyzes The enzyme from B. sphaericus catalyzes the transfer of pro S (B) hydrogen from NADH. PMID- 3112145 TI - Phosphorylation site of eukaryotic initiation factor 4E. AB - Eukaryotic protein synthesis initiation factor 4E (eIF-4E) was labeled in situ with [32P]orthophosphate in cultured HeLa cells and rabbit reticulocytes and purified by affinity chromatography. Tryptic digestion yielded one labeled peptide which contained predominantly serine and lysine. After treatment of the protein with citraconic anhydride to block epsilon-amino groups of lysyl residues, tryptic digestion yielded a labeled peptide whose composition was consistent with the structure Trp-Ala-Leu-Trp-Phe-Phe-Lys-Asn-Asp-Lys-Ser(P)-Lys Thr-Trp-Gln-Ala-Asn-L eu-Arg, one of the arginyl peptides predicted from the human eIF-4E cDNA sequence. The only serine in this peptide is located at position 53 of eIF-4E. Thus, it is concluded that eIF-4E contains a single site of phosphorylation for an endogenous protein kinase, which is Ser-53 in the human eIF-4E sequence. PMID- 3112143 TI - Glucocorticoids inhibit the liberation of arachidonate but not the rapid production of phospholipase C-dependent metabolites in acetylcholine-stimulated C62B glioma cells. AB - We have previously demonstrated that if C62B glioma cells are prelabeled with [1 14C]arachidonate, cholinergic stimulation results in liberation of radioactive arachidonate and accumulation of radioactive phosphatidate. Cells prelabeled with [2-3H]inositol and stimulated with acetylcholine in the presence of 25 mM LiCl accumulate glycerophosphoinositol and inositol phosphates. The acetylcholine stimulated accumulation of these products is indicative of activation of both phospholipases A2 and C. When prelabeled cells are pretreated overnight with dexamethasone prior to acetylcholine stimulation, there is preferential inhibition of those products dependent upon phospholipase A2 activity (arachidonate and glycerophosphoinositol accumulation are inhibited 77 and 63%, respectively). During the same time period when phospholipase A2-dependent products are accumulating, there is little effect on the production of phospholipase C-dependent products (acetylcholine-stimulated accumulation of phosphatidate or of inositol phosphates was inhibited by less than 10%). Treatment of C62B cells with two other glucocorticoids, betamethasone and cortisone, produced results similar to those of dexamethasone as did treatment with quinacrine, a phospholipase A2-selective inhibitor. Pretreatment of C62B cells with the mineralocorticoid, aldosterone, did not alter acetylcholine stimulated response. These results suggest that glucocorticoid treatment results in a preferential inhibition of phospholipase A2 with little effect on the generation of phospholipase C products. PMID- 3112144 TI - Inactivation of isocitrate dehydrogenase by phosphorylation is mediated by the negative charge of the phosphate. AB - The control of isocitrate dehydrogenase through phosphorylation is necessary for growth of Escherichia coli on acetate as the sole carbon source. To understand the mechanism by which phosphorylation inactivates isocitrate dehydrogenase, the sequence of icd, the isocitrate dehydrogenase structural gene, was determined and this information was used to construct mutants at the site of phosphorylation. Introduction of a negatively charged aspartate for the serine that is phosphorylated completely inactivates isocitrate dehydrogenase. Substitution of the serine with other amino acids results in a partially active enzyme in which both maximal velocity and interaction with substrates has been altered. Neither threonine nor tyrosine, when substituted for the serine at the phosphorylation site, is detectably phosphorylated by isocitrate dehydrogenase kinase. PMID- 3112146 TI - Tyrosinase-catalyzed unusual oxidative dimerization of 1,2-dehydro-N acetyldopamine. AB - Tyrosinase, which usually catalyzes the conversion of o-diphenols to o benzoquinones, catalyzed an unusual oxidative dimerization of 1,2-dehydro-N acetyl-dopamine to a benzodioxan derivative. The identity of the product was confirmed by UV, IR spectra, and NMR studies. During the oxidation, generation of a transient reactive intermediate could be witnessed by its characteristic visible absorption spectrum. Typical phenoloxidase inhibitors such as phenylthiourea, potassium cyanide, sodium azide, and sodium fluoride drastically inhibited the above reaction. Mimosine, a known competitive inhibitor of o diphenoloxidase activity, also inhibited the new reaction competitively, suggesting that both the observed oxidative dimerization and the conventional quinone production are catalyzed by the same active site copper of tyrosinase. Based on our earlier findings (Sugumaran, M., and Lipke, H. (1983) FEBS Lett. 155, 65-68; Sugumaran, M. (1986) Biochemistry 25, 4489-4492) that phenoloxidases can produce quinone methides from certain 4-alkylcatechols, possible mechanisms for this new reaction are presented. PMID- 3112147 TI - Characterization of the core protein of the large chondroitin sulfate proteoglycan synthesized by chondrocytes in chick limb bud cell cultures. AB - The core protein of high buoyant density proteoglycans synthesized by chondrocytes in stage 24 chick limb bud mesenchymal cell cultures was cleaved with cyanogen bromide to produce 17 resolvable peptides on sodium dodecyl sulfate polyacrylamide slab gels. Of these peptides, 10 appear to originate from the chondroitin sulfate-rich region, 2 appear to be derived from the keratan sulfate rich region, and 5 seem to be derived from the hyaluronic acid-binding region. The peptides from the chondroitin sulfate-rich region are almost all large (200 to 64 kDa). In contrast, the peptides from the keratan sulfate-rich and hyaluronic acid-binding regions are relatively small (47 to 12 kDa). One peptide from the hyaluronic acid-binding region appears to contain mannose-rich N-linked oligosaccharides as inferred from its observed binding by concanavalin A. A different hyaluronic acid-binding region peptide and one of the keratan sulfate rich peptides were shown to contain disulfide bonds and therefore may be involved in contributing to the tertiary structure of the hyaluronic acid-binding region. Based on these observations, a map of the chick chondrocyte proteoglycan core protein has been constructed. PMID- 3112148 TI - Modulation of alveolar macrophage-derived 5-lipoxygenase products by the sulfhydryl reactant, N-ethylmaleimide. AB - The sulfhydryl reactant N-ethylmaleimide (NEM) stimulates the release and cyclooxygenase metabolism of arachidonic acid in rat alveolar macrophages. Because both 5-lipoxygenation and leukotriene (LT) C4 synthesis represent sulfhydryl-dependent steps in the 5-lipoxygenase pathway, we examined the effect of NEM on 5-lipoxygenase, as well as cyclooxygenase, metabolism in resting and agonist-stimulated cells by reverse-phase high performance liquid chromatography and radioimmunoassay. NEM at 5-10 microM stimulated the synthesis of thromboxane, but not prostaglandin E2 or the 5-lipoxygenase products LTC4, LTB4, or 5 hydroxyeicosatetraenoic acid from endogenously released arachidonate. In the presence of exogenous fatty acid, however, NEM stimulated the synthesis of large quantities of LTB4. The effect of NEM on arachidonate metabolism stimulated by the calcium ionophore A23187 and the particulate zymosan was also investigated. NEM augmented arachidonate release and thromboxane synthesis stimulated by A23187 but inhibited A23187-induced LTC4 synthesis with an IC50 of approximately 4.3 microM. This inhibitory effect closely paralleled the ability of NEM to deplete intracellular glutathione (IC50 approximately 4.3 microM). Preincubation with the intracellular cysteine delivery agent L-2-oxothiazolidine-4-carboxylate augmented intracellular glutathione concentration and A23187-stimulated LTC4 synthesis and attenuated the capacity of NEM to deplete glutathione and inhibit LTC4 synthesis. While LTB4 and 5-hydroxyeicosatetraenoic synthesis were unaffected at these low NEM concentrations, LTB4 synthesis was inhibited at high concentrations (IC50 approximately 210 microM). Zymosan-induced eicosanoid synthesis was modulated by NEM in a similar fashion. Thus, NEM is an agonist of arachidonate metabolism with the capacity to modulate the spectrum of macrophage-derived eicosanoids by virtue of specific biochemical interactions with substrates and enzymes of the 5 lipoxygenase pathway. PMID- 3112149 TI - Regulation of G-proteins in differentiation. Altered ratio of alpha- to beta subunits in 3T3-L1 cells. AB - The complexion of the adenylate cyclase system and in particular, the regulation of G-proteins was examined in 3T3-L1 cells during differentiation from a fibroblast-like to an adipocyte-like phenotype. Gs alpha (the identified regulatory component of hormone-sensitive adenylate cyclase that mediates stimulation), measured by cholera toxin-catalyzed ADP-ribosylation, increased by approximately 6-fold from day 0 to day 8. Gs alpha, measured by functional reconstitution, increased in specific activity by approximately 3-fold from day 0 to day 8. Both Gi alpha (the G-protein with alpha-subunit Mr 40,000-41,000 whose function is in part the mediation of inhibition of adenylate cyclase) and Go alpha (the highly abundant G-protein first isolated from bovine brain whose effector system remains to be established) measured by pertussis toxin-catalyzed ADP-ribosylation increased by approximately 4-fold over this same period. 3T3-L1 cells possess beta-subunits of G-proteins displaying Mr = 36,000 (beta 36) and Mr = 35,000 (beta 35). The increase in the beta 35 as well as beta 36 subunits was approximately 2-fold. Using quantitative immunoblotting techniques and specific antisera, the total amount of beta-subunits was determined to be 150 as compared to 70 pmol/mg of membrane protein, while the amount of Go alpha was 40 and 10 pmol/mg of membrane protein in adipocytes and fibroblasts, respectively. Since Go alpha is the most abundant G-protein alpha-subunit observed to date in both phenotypes, the overall ratio of beta- to alpha-subunits of G-proteins appears to decrease from approximately 4.7 in fibroblasts to 2.5 in adipocytes. These data suggest that in differentiation not only is the complexion of G-proteins altered but more importantly, the relative amounts of alpha- to beta-subunits are regulated. PMID- 3112150 TI - Site-specific mutagenesis of the alpha subunit of tryptophan synthase from Salmonella typhimurium. Changing arginine 179 to leucine alters the reciprocal transmission of substrate-induced conformational changes between the alpha and beta 2 subunits. AB - Arginine 179 of the alpha subunit of tryptophan synthase of Salmonella typhimurium was changed to leucine by site-directed mutagenesis. The mutant alpha subunit was expressed in S. typhimurium, purified and crystallized as the alpha 2 beta 2 complex, and characterized by kinetic studies under steady-state reaction conditions. The rate of cleavage of indole 3-glycerol phosphate (alpha reaction) is reduced by 60% in the mutant alpha 2 beta 2 complex, whereas the rate of L tryptophan synthesis from indole and L-serine (beta reaction) is unchanged. Thus, arginine 179 is not obligatory for catalysis, for binding of indole 3-glycerol phosphate, or for interaction of the alpha and beta 2 subunits. However, changing arginine 179 to leucine does have striking effects on ligand-dependent properties of this multienzyme complex. Ligands of the alpha subunit (DL-alpha glycerophosphate and indole 3-propanol phosphate) which strongly inhibit the beta reaction of the native alpha 2 beta 2 complex have a slight stimulatory effect on the beta reaction of the mutant alpha 2 beta 2 complex. Likewise, L-serine, a ligand of the beta subunit which produces a 5-fold reduction in the Km for the alpha ligand indole 3-glycerol phosphate in the native alpha 2 beta 2 complex, has no effect on the mutant alpha 2 beta 2 complex. These results suggest that arginine 179 of the alpha subunit plays a role in the reciprocal transmission of substrate-induced conformational changes which occur between native alpha and beta 2 subunits in the alpha 2 beta 2 complex. PMID- 3112151 TI - The human T3 gamma chain is phosphorylated at serine 126 in response to T lymphocyte activation. AB - The gamma subunit of the human T lymphocyte T3 antigen is rapidly phosphorylated on serine residues in vivo during the initiation of T cell activation by a polyclonal mitogen (Phaseolus vulgaris phytohemagglutinin), an activator of protein kinase C (phorbol 12,13-dibutyrate), and an elevator of intracellular calcium (ionomycin). The sites of phosphorylation were identified by comparing tryptic peptide analyses of T3 gamma chains labeled in vivo with various synthetic peptides, corresponding to portions of the cytoplasmic domain of the gamma chain that had been labeled in vitro using purified protein kinase C. Two sites, serines 123 and 126, were phosphorylated in response to ionomycin, whereas a single site, serine 126, was phosphorylated when T lymphocytes were stimulated by P. vulgaris phytohemagglutinin or when protein kinase C was directly activated by phorbol 12,13-dibutyrate. Immune activation of T cells via the protein kinase C pathway thus induces phosphorylation of a single site on the T3 gamma chain, namely serine 126. PMID- 3112152 TI - Synthesis in vitro of 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 by interferon-gamma-stimulated normal human bone marrow and alveolar macrophages. AB - Cultured human macrophages from normal donors were examined for their capability to metabolize 25-hydroxyvitamin D3 (25-(OH)D3). Upon exposure to recombinant human interferon-gamma (IFN-gamma) both bone marrow-derived macrophages (BMM) and pulmonary alveolar macrophages (PAM) produced a polar 25-(OH)D3 metabolite which was purified from conditioned media and unequivocally identified as 1,25 dihydroxyvitamin D3 (1,25-(OH)2D3) by UV-absorbance spectrophotometry and mass spectrometry. The BMM and PAM also synthesized a second 25-(OH)D3 metabolite which was structurally identified as 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3). The time course of 25-(OH)D3 metabolism by macrophages suggested that the production of 24,25-(OH)2D3 was stimulated by high intracellular levels of 1,25 (OH)2D3 and not by IFN-gamma. The 1,25-(OH)2D3 obtained from BMM and PAM promoted macrophage-like differentiation of promyelocytic HL-60 leukemia cells and inhibited IFN-gamma production by normal human lymphocytes. Our data suggest that locally high levels of 1,25-(OH)2D3 in the microenvironment of IFN-gamma stimulated BMM and PAM may modulate the function of hormone-responsive cells. PMID- 3112153 TI - Synthesis of dolichol derivatives in trypanosomatids. Characterization of enzymatic patterns. AB - We have previously described that in certain parasitic protozoa, namely the trypanosomatids, the dolichol-P-P-linked oligosaccharides synthesized in vivo and transferred to protein are devoid of glucose residues and contain 6, 7, or 9 mannose units depending on the species. We have now conducted a cell-free characterization of the enzymatic patterns responsible for these phenotypes. Microsomes from Trypanosoma cruzi, Crithidia fasciculata, Leishmania enriettii, and Blastocrithidia culicis were found to synthesize dolichol-P-[14C]Man but not dolichol-P-[14C]Glc when incubated with rat liver dolichol-P and GDP-[14C]Man or UDP-[14C]Glc, thus providing for an explanation to the absence of glucosylated dolichol-P-P derivatives. Formation of dolichol-P-P-oligosaccharides was assayed in incubation mixtures containing rat liver dolichol-P, GDP-[14C]Man, microsomes, and unlabeled Man5-8GlcNAc2-P-P-dolichol from bovine liver. Membranes from species synthesizing dolichol-P-P-linked Man6GlcNAc2 or Man7GlcNAc2 in vivo were found to synthesize the same compounds but not the higher homologues in the cell free assay. Species forming Man9GlcNAc2-P-P-dolichol in vivo were found to synthesize lipid-linked Man7GlcNAc2, Man8GlcNAc2, and Man9GlcNAc2 in vitro. It is concluded that there are at least three and probably four different dolichol-P Man-dependent enzymatic activities involved in the synthesis of dolichol-P-P linked Man9GlcNAc2 and that microorganisms not forming that compound are devoid of all mannosyltransferases responsible for the addition of the missing residues and not only of the enzyme involved in the synthesis of the homologue higher than the oligosaccharide occurring in vivo by a single mannose unit. PMID- 3112154 TI - Examination of the role of arginine-143 in the human copper and zinc superoxide dismutase by site-specific mutagenesis. AB - The active site arginine-143 of human Cu,Zn superoxide dismutase has been replaced by lysine or by isoleucine. The mutant proteins were expressed at high levels in yeast, purified, and the amino acid substitution explored through the use of group specific reagents. The specific activities of these enzymes, measured by the xanthine oxidase/cytochrome c method and by using dry weight determination to establish protein concentration, were: native enzyme, 6570 units/mg; Lys-substituted enzyme, 2840 units/mg, Ile-substituted enzyme, 708 units/mg. The active site arginine thus plays an important, but not an essential, role in the catalytic process. PMID- 3112155 TI - Guanosine 5'-O-(3-thiotriphosphate) reduces ADP-ribosylation of the inhibitory guanine nucleotide-binding regulatory protein of adenylyl cyclase (Ni) by pertussis toxin without causing dissociation of the subunits of Ni. Evidence of existence of heterotrimeric pt+ and pt- conformations of Ni. AB - The effect of the addition of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), the GTP analog which activates the inhibitory guanine nucleotide-binding regulatory protein of adenylyl cyclase (Ni), on the pertussis toxin-mediated ADP ribosylation reaction was studied in detail. Two effects were discerned: a stimulation of the ADP-ribosyltransferase activity of the toxin, akin to what was described for ATP and GDP in a previous report (Mattera, R., Codina, J., Sekura, R., and Birnbaumer, L. (1986) J. Biol. Chem. 261, 11173-11179), and a decrease in the ability of Ni to be a substrate for the activated toxin. Both effects were time-dependent with activation of the toxin being somewhat faster than inactivation of Ni. The effect of the addition of GTP gamma S on Ni was readily reversed by excess GDP and attenuated by increasing EDTA in the medium from 0.35 to 10 mM, suggesting dependence on trace concentrations of a divalent cation. It is suggested that this cation is Mg2+ on the basis that low (5-10 nM) concentrations of Mg2+ are needed for the endogenous GTPase activity of Ni (Sunyer, T., Codina, J., and Birnbaumer, L. (1984) J. Biol. Chem. 259, 15447 15451). Sucrose density gradient analysis of the Ni X GTP gamma S complexes with decreased susceptibility to ADP-ribosylation by pertussis toxin showed the same sedimentation parameters as Ni or Ni X GDP complexes, indicating that the molecule of Ni with GTP gamma S bound is heterotrimetric as opposed to dissociated into alpha i X GTP gamma S plus beta X gamma. Thus, these experiments define two conformations of heterotrimeric Ni: one -pt+, ADP-ribosylated by pertussis toxin, and the other pt-, poorly or not ADP-ribosylated by pertussis toxin. This latter, hitherto unrecognized conformation, is stabilized by the addition of strongly activating guanine nucleotides such as GTP gamma S and guanyl-5'-yl imidodiphosphate and should be important in the train of events that lead from an inactive heterotrimeric Ni to a fully active and dissociated Ni. PMID- 3112157 TI - Type XI collagen is a heterotrimer with the composition (1 alpha, 2 alpha, 3 alpha) retaining non-triple-helical domains. AB - Three collagen chains, 1 alpha, 2 alpha, and 3 alpha, have previously been identified in the cartilaginous extracellular matrix and have been referred to collectively as type XI collagen. The structure of type XI is poorly defined. Neither the organization of these collagen chains into trimeric molecules nor the extent of proteolytic processing has been adequately determined. Formaldehyde derived covalent cross-links were introduced into the native molecules. As judged by velocity sedimentation, the cross-links formed were predominantly intramolecular and led to the formation of covalent trimeric molecules. Chromatographic analysis of trimers is most consistent with a heterotrimer (1 alpha, 2 alpha, 3 alpha) being the predominant form. To investigate the structure of type XI as it occurs in the matrix, sterna from chick embryos treated with beta-aminopropionitrile were solubilized without proteolysis with pepsin. Electrophoretic analysis revealed that all three chains of type XI retain non triple-helical domains. Some heterogeneity was observed in the size of the 1 alpha chain. Metabolic labeling and long term chase experiments suggested that this heterogeneity in the size of 1 alpha may be due to slow or incomplete posttranslational proteolytic processing. PMID- 3112156 TI - Oncofetal expression of Lex carbohydrate antigens in human colonic adenocarcinomas. Regulation through type 2 core chain synthesis rather than fucosylation. AB - The mechanism of expression of a series of glycolipid antigens carrying the Lex determinant structure, Gal beta 1----4[Fuc alpha 1----3]GlcNAc beta 1----, and characterized by oncofetal expression in fetal colon and colonic adenocarcinomas has been studied in human fetal and adult proximal colon tissue. Results presented from TLC immunostain analysis of neutral glycolipids isolated from normal adult colonic mucosa have indicated the presence of only barely detectable quantities of both an Lex-active glycolipid that co-migrated with III3V3Fuc2nLc6 and its precursor nLc6. These structures were found in large quantities in glycolipid fractions from human adenocarcinoma tumors and human small cell lung carcinoma NCI-H69 cells. In contrast, type 1 chain-based Lea antigen structures were found in both normal mucosa and adenocarcinomas. Analysis of gangliosides of normal colonic mucosa by TLC immunostain indicated the presence of a series of type 2 chain-based gangliosides; however, sialyl-Lex was not detected. The ability of normal colonic mucosa to synthesize type 2 chain core structures was demonstrated by the presence of a beta 1----4 galactosyltransferase activity with Lc3 as an acceptor in an amount equivalent to 60-65% of the total galactosyltransferase activity. An alpha 1----3 fucosyltransferase was also found to be expressed in significant quantity in adult colonic mucosa. Kinetic studies indicated that this is most probably the alpha 1----3/4 fucosyltransferase suggested to be a product of the Lewis gene (Le). Thus, although normal adult colonic mucosa contained the enzymes to synthesize Lex and sialyl-Lex structures, these antigens were not found. Tissue immunofluorescence studies indicated that type 2 chain precursors and the alpha 1----3/4 fucosyltransferase were found in different cell populations in adult proximal colonic mucosa. However, both type 2 chain core structures and their fucosylated derivatives were found to be associated with epithelial cells of fetal colon. These results indicate that oncofetal expression of Lex antigens in fetal colonic epithelium and in adenocarcinomas but not in normal adult mucosa is due to the retrogenetic expression of type 2 chain precursors which are not found in normal adult colonic epithelial cells. PMID- 3112158 TI - Missense misreading of asparagine codons as a function of codon identity and context. AB - During asparagine starvation the frequency of lysine for asparagine substitutions increases to levels that enable one to isolate and sequence mistranslated protein. We have used site-directed mutagenesis to construct a series of derivatives of the gene encoding the coat protein of the bacteriophage MS2. The mutant set constructed has either AAU or AAC as codon three in the gene with each possible adjoining 3' base. Lysine incorporation in coat protein encoded by these genes shows that AAU is misread from 4- to 9-fold more frequently than AAC with any 3' context. Although in some cases context effects of approximately 2-fold were noted, there seems to be no simple hypothesis to explain them. PMID- 3112159 TI - Intracellular localization of lactosylceramide, the major human neutrophil glycosphingolipid. AB - The abundance of lactosylceramide (LacCer; Gal beta 1-4Glc beta 1-1Cer) in human polymorphonuclear neutrophils (PMN) (about 10(9) molecules/cell) seemed inconsistent with an exclusive plasma membrane LacCer localization in these cells. Therefore, the distribution of LacCer between plasma membrane and intracellular compartments was analyzed. Binding of 125I-labeled monoclonal anti LacCer antibody (T5A7) to intact cells indicated that only 0.1-0.2% of total LacCer was accessible to antibody. Chemical and immunochemical comparisons of organic extracts prepared from PMN cytoplasts (i.e. PMN depleted of nucleus and granules) and intact PMN demonstrated that less than 25% of PMN LacCer was plasma membrane-derived. Simultaneous particle volume and surface staining analyses suggested that selective LacCer loss from cytoplasts could not explain this result. Intracellular LacCer was demonstrated by intense staining of PMN frozen thin sections with T5A7 in indirect immunofluorescence tests. Two-color fluorescence studies using frozen thin sections of neutrophils previously surface stained with saturating concentrations of T5A7 indicated that this staining did not reflect section artifact. Organic extracts of density gradient-fractionated PMN cavitates were analyzed by radioimmunoassay to determine whether LacCer associates with known populations of PMN granules. Antigen predominantly cosedimented with enzyme markers for primary and secondary granules rather than with plasma membrane marker. Thin layer chromatography of glycolipids extracted from these density gradient fractions identified LacCer as the only antigenic species and demonstrated that chemically detectable LacCer was primarily in granule-enriched rather than plasma membrane fractions. These data indicate that human PMN LacCer is predominantly intracellular and that the glycolipid may be a constituent of PMN lysosomal granules. PMID- 3112160 TI - Expression of cDNAs for G proteins in Escherichia coli. Two forms of Gs alpha stimulate adenylate cyclase. AB - Complementary DNAs that encode two forms of the alpha subunit (Gs alpha) of the guanine nucleotide-binding protein responsible for stimulation of adenylate cyclase (Gs) have been inserted into plasmid vectors for expression in Escherichia coli. Following transformation of either of these plasmids into E. coli K38, Gs alpha accumulates to 0.4-0.8 mg/liter (approximately 0.1% of total protein), as judged by immunoblot analysis with specific antisera. Based on deduced amino acid sequence, the two cDNAs should encode proteins with molecular weights of 44,500 and 46,000, respectively (Robishaw, J.D., Smigel, M. D., and Gilman, A. G. (1986) J. Biol. Chem. 261, 9587-9590). Expression of these cDNAs in E. coli yields proteins that co-migrate on sodium dodecyl sulfate-polyacrylamide gels with the Gs alpha subunits from S49 lymphoma cell membranes, with apparent molecular weights of 45,000 and 52,000, respectively. Low levels of activity are detected in the 100,000 X g supernatant after lysis and fractionation of E. coli expressing either form of Gs alpha. Partial purification of Gs alpha from E. coli lysates yields preparations in which significant and stable activity can be assayed. Both forms of Gs alpha migrate through sucrose gradients as soluble, monodisperse species in the absence of detergent. As expressed in E. coli, both forms of Gs alpha can reconstitute isoproterenol-, guanine nucleotide-, and fluoride-stimulated adenylate cyclase activity in S49 cyc-cell membranes to approximately the same degree and can be ADP-ribosylated with [32P]NAD+ and cholera toxin. However, based on the specific activity of purified rabbit liver Gs, only 1-2% of the Gs alpha expressed in E. coli appears to be active. Incubation of partially purified fractions of recombinant Gs alpha with guanosine 5'-(3-O-thio)triphosphate and resolved beta gamma subunits isolated from purified bovine brain G proteins results in a 7-10-fold increase in Gs activity. Incubation of bovine brain beta gamma with recombinant Gs alpha also leads to a dramatic increase in observed levels of cholera toxin-catalyzed [32P]ADP ribosylation. PMID- 3112161 TI - Cervical cord compression from ossification of the posterior longitudinal ligament in non-orientals. AB - We report 14 cases of symptomatic ossification of the posterior longitudinal ligament (OPLL) diagnosed in non-oriental men between 1978 and 1985. All 14 patients had incomplete spinal cord syndromes due to OPLL in the cervical spine and had been referred undiagnosed from other institutions. Twelve had severe myelopathy and seven were wheelchair-bound before OPLL was diagnosed, while six patients had had operations elsewhere for their neurological dysfunction. There was a close association between OPLL and diffuse idiopathic skeletal hyperostosis (Forestier's disease) on plain radiographs, seven patients having both disorders. Enhanced CT scans proved to be the best diagnostic method for the localisation of cord compression, and magnetic resonance imaging, used on four recent cases, provided the best visualisation of the extent of involvement in the sagittal plane. We aim to heighten awareness of OPLL in non-orientals, in whom the clinical features, histological characteristics, and radiographic patterns are very similar to those of oriental patients. PMID- 3112162 TI - Diagnosis-related groupings (DRGs) and wound closure: roundtable discussion. PMID- 3112163 TI - "Borrowed" burn nurses: a cost-effective option for providing skilled staff during periods of need. AB - Staffing a burn center with qualified nurses is difficult because of highly variable patient census and the diversity and complexity of required nursing knowledge and skills. There are disadvantages to relying on usual temporary sources of supplemental staff. A viable alternative is the "borrowing" of burn nurses from another burn center during periods of high census. This solution has proved to be cost-effective and functional. PMID- 3112164 TI - Will burn centers survive another round of budget cuts? PMID- 3112165 TI - An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy. AB - Scanning confocal microscopes offer improved rejection of out-of-focus noise and greater resolution than conventional imaging. In such a microscope, the imaging and condenser lenses are identical and confocal. These two lenses are replaced by a single lens when epi-illumination is used, making confocal imaging particularly applicable to incident light microscopy. We describe the results we have obtained with a confocal system in which scanning is performed by moving the light beam, rather than the stage. This system is considerably faster than the scanned stage microscope and is easy to use. We have found that confocal imaging gives greatly enhanced images of biological structures viewed with epifluorescence. The improvements are such that it is possible to optically section thick specimens with little degradation in the image quality of interior sections. PMID- 3112166 TI - Characterization of a Drosophila protein that binds both epidermal growth factor and insulin-related growth factors. AB - The identification of a novel protein from Drosophila melanogaster that binds both mammalian epidermal growth factor (EGF) and insulin has been reported (Thompson, K. L., S. J. Decker, and M. R. Rosner, 1985, Proc. Natl. Acad. Sci. USA., 82:8443-8447). This 100-kD protein (designated dp100) is also recognized by an antiserum against the human EGF receptor. To further characterize the properties of this protein, we have determined the binding spectrum, glycosylation state, and cellular distribution of dp100. Our results indicate that dp100 binds to other insulin-like and EGF-like growth factors with dissociation constants ranging from 10(-6) to 10(-9) M, and these ligands compete with each other for binding to dp100. All other ligands tested, including platelet-derived growth factor, transforming growth factor-beta, nerve growth factor, and glucagon, either did not bind or bound with a Kd greater than 10(-6) M. Unlike the Drosophila insulin receptor, dp100 does not bind to wheat germ agglutinin and is present in a cytoplasmic as well as a membrane-bound form that cannot be differentiated by two-dimensional PAGE. Further, dp100 is the sole transforming growth factor-alpha-binding protein detected by affinity labeling in Drosophila Kc cells. These results indicate that dp100 shares properties in common with, but distinct from, the Drosophila homologues of the insulin and EGF receptors. PMID- 3112168 TI - Phosphorylation and dephosphorylation of soluble proteins in human eosinophils. AB - The effect of phorbol 12-myristate 13-acetate (PMA), calcium ionophore (A23187), opsonized zymosan (OZ), and N-formylmethionyl-leucyl-phenylalanine (f-Met-Leu Phe) on protein phosphorylation was examined in purified eosinophils (eos) isolated from human peripheral blood. Eos were prelabeled with [32P]orthophosphate, stimulated with several activating agents for varying periods of time. The soluble proteins were then analyzed by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. In resting eos, there was phosphorylation of endogenous soluble proteins with molecular weights of 12, 16, 21, 40, and 66 kilodaltons (kDa). PMA, a potent activator of oxidative metabolism, induced phosphorylation of 19-, 40-, and 67-kDa proteins. A23187, a strong degranulating stimulus, caused phosphorylation of 40-, 53-, and 67-kDa proteins. OZ, a relatively weak stimulus for eos function, caused phosphorylation of 30-34-, 59-, 67-, and 93-kDa proteins. In addition, all the above stimuli caused a time-dependent dephosphorylation of 21-kDa protein. In contrast, f-Met-Leu-Phe caused neither phosphorylation of new proteins nor dephosphorylation of preexisting eos proteins. These findings demonstrate that selected stimuli affect phosphorylation of soluble eos protein. These results also suggest that phosphorylation of specific proteins in eos is an intermediary step in external stimulus-induced cell activation, which may involve many different cell functions. PMID- 3112167 TI - A three-dimensional approach to mitotic chromosome structure: evidence for a complex hierarchical organization. AB - We describe findings on the architecture of Drosophila melanogaster mitotic chromosomes, made using a three-dimensional-oriented structural approach. Using high-voltage and conventional transmission electron microscopy combined with axial tomography and digital contrast-enhancement techniques, we have for the first time visualized significant structural detail within minimally perturbed mitotic chromosomes. Chromosomes prepared by several different preparative procedures showed a consistent size hierarchy of discrete chromatin structural domains with cross-sectional diameters of 120, 240, 400-500, and 800-1,000 A. In fully condensed, metaphase-arrested chromosomes, there is evidence for even larger-scale structural organization in the range of 1,300-3,000-A size. The observed intrachromosomal arrangements of these higher-order structural domains show that both the radial loop and sequential helical coiling models of chromosome structure are over-simplifications of the true situation. Finally, our results suggest that the pathway of chromatin condensation through mitosis consists of concurrent changes occurring at several levels of chromatin organization, rather than a strictly sequential folding process. PMID- 3112169 TI - Reduction of cerebrospinal fluid pressure by hypocapnia: changes in cerebral blood volume, cerebrospinal fluid volume, and brain tissue water and electrolytes. AB - The study examined the role of cerebral blood volume (CBV), cerebrospinal fluid (CSF) volume, and brain tissue water and electrolytes on CSF pressure during 4 h of hypocapnia in dogs. Group I (n = 6) was examined during hypocapnia (PaCO2 20 mm Hg), with no intracranial mass being present. Group II (n = 6) was examined with an intracranial mass present (epidural balloon, CSF pressure 35 cm H2O), but no hypocapnia. In group III (n = 6), an intracranial mass was present, and hypocapnia was used to lower CSF pressure. In group I, hypocapnia initially reduced CBV from 3.4 to 2.4 ml. With continued hypocapnia, CBV reexpanded to 3.4 ml by 4 h. CSF volume changed reciprocally, so that intracranial CSF pressure remained constant. In group II, CBV remained steady (2.7 ml), and CSF volume fell only slightly, so that CSF pressure remained elevated. In group III, hypocapnia initially reduced CBV from 2.8 to 2.2 ml, and CSF pressure fell from 35 to 19 cm H2O. With continued hypocapnia, CBV rose to 2.8 ml by 4 h, but CSF volume fell from 6.1 to 5.0 ml, so that CSF pressure remained low. Net intracranial absorption of CSF did not exceed net intracranial CSF production, suggesting that CSF volume fell because hypocapnia improved access of intracranial CSF to spinal sites of CSF reabsorption. Brain tissue composition was not different among groups. The results indicate that hypocapnia lowers elevated CSF pressure initially by lowering CBV. This CSF pressure-lowering effect is sustained (despite reexpansion of CBV) by a further reduction of CSF volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112170 TI - [Peroperative radiotherapy. Initial experience at the Red Cross Hospital]. AB - Intra operative radiation therapy is a new look at an old idea (Rich). In relation with the first experience at the Croix-Rousse Hospital with orthovoltage, a review of technical choices, surgical problems, and biological questions is presented. The analysis of literature about accumulated clinical results suggest that local control in recurrence, residual, or inoperable tumor can be obtained by combined surgery IOR, and external beam irradiation. This short experience demonstrate the feasibility of the treatment as a routine and emphasizes the need for continued study. PMID- 3112171 TI - Determination of flecainide by gas chromatography-mass spectrometry. PMID- 3112172 TI - T-cell surface molecules involved in the induction and expression of lymphokine activated killing of autologous and allogeneic tumor targets. AB - The cellular interactions and the surface molecules involved in the generation and the expression of lymphokine-activated killer-cell (LAK) activities in vitro in blood mononuclear cells (BMN) from cancer patients and healthy individuals against autologous and allogeneic tumors were studied. The depletion of a plastic adherent population(s) from BMN at the initiation of in vitro cultures in recombinant interleukin-2 (rIL-2) markedly interfered with the generation of LAK activities. Readdition of the same number of irradiated autologous plastic adherent cells to the nonadherent population restored the generation of LAK. The requirement of the plastic-adherent population(s) in in vitro induction of LAK activities was observed only in autologous situations. Furthermore, selective modulations of CD3 and CD2 receptors on BMN with the appropriate monoclonal antibodies (MAb) during the induction phases of LAK responses profoundly inhibited the generation of LAK. Thus, unhindered expression of CD2 molecules and CD3 molecules were necessary for the maximum cytotoxic activation of non-antigen driven effector cells in short-term cultures in rIL-2. PMID- 3112174 TI - [Studies on arachidonic acid-induced brain ischemia and the difference in severity between SHRSR and WKY rats]. PMID- 3112173 TI - Patients with condyloma acuminatum exhibit decreased interleukin-2 and interferon gamma production and depressed natural killer activity. AB - Peripheral blood mononuclear cells were obtained from 20 untreated condyloma acuminatum patients and from an equal number of sex- and age-matched controls and assayed for cell surface antigen expression, natural killer activity, and lymphokine production. Patient peripheral blood mononuclear cells had significantly lower helper-to-suppressor T-cell ratios (Leu3/Leu2) (P less than 0.05) and significantly higher percentages of Leu 2+ Tac+ cells (activated suppressor/cytotoxic cells) (P less than 0.05) and Leu 2+ OKM1+ cells (suppressor cells) (P less than 0.01). Natural killer activity of condyloma acuminatum patients was significantly lower (P less than 0.05) than that of controls. Production of interleukin-2 and interferon gamma, but not interferon alpha, was significantly (P less than 0.01) decreased in condyloma acuminatum patients. There was an inverse correlation between the in vitro production of interleukin-2 and interferon gamma and the percentage of Leu 2+ OKM1+ cells (suppressor) (P less than 0.01). Thus, patients with condyloma acuminatum differ from controls by demonstrating decreased natural killer-cell activity, decreased production of lymphokines which enhance natural killer-cell activity (i.e., interferon gamma and interleukin-2), and an increased proportion of T cells with a suppressor phenotype. PMID- 3112176 TI - In vitro activity of Ro 19-5247 (T-2525) and interpretive criteria for disk diffusion susceptibility testing. AB - The activity of Ro 19-5247 (the active metabolite of the oral cephalosporin Ro 19 5248 [T-2588]) was compared with that of five orally active agents against a total of 331 bacterial strains. Ro 19-5247 was more active in vitro than amoxicillin, amoxicillin-clavulanate, cefaclor, cefuroxime, and cephalexin against members of the family Enterobacteriaceae. Amoxicillin-clavulanate and amoxicillin overall were more active than the other four agents against staphylococci. Ro 19-5247, amoxicillin-clavulanate, amoxicillin, and cefuroxime were equally active against nonenterococcal streptococci and more active than cefaclor and cephalexin. All six agents showed little or no activity against nonfermentative gram-negative bacteria. Against Streptococcus (Enterococcus) faecalis, only amoxicillin and amoxicillin-clavulanate were active. The interpretive criteria for in vitro susceptibility testing with 10- and 30 micrograms Ro 19-5247 disks were established by regression analysis to correlate the inhibitory zone sizes and MICs for the bacterial isolates. The suggested tentative zone size breakpoints for the 10-micrograms disk are as follows: susceptible, greater than or equal to 22 mm (MIC, less than or equal to 2 micrograms/ml); moderately susceptible, 20 to 21 mm (MIC, 4 micrograms/ml); and resistant, less than or equal to 19 mm (MIC, greater than or equal to 8 micrograms/ml). PMID- 3112175 TI - Expression of proteins of Mycobacterium tuberculosis in Escherichia coli and potential of recombinant genes and proteins for development of diagnostic reagents. AB - Recombinant plasmids containing DNA from Mycobacterium tuberculosis were transformed into Escherichia coli, and three colonies were selected by their reactivity with polyclonal antisera to M. tuberculosis. The three recombinant vectors contained DNA inserts of different sizes flanking a common 4.7-kilobase (kb) sequence. Each recombinant produced 35- and 53-kilodalton proteins (35K and 53K proteins, respectively) which were absent in the control E. coli. In Western blotting experiments, both proteins bound several antisera to M. tuberculosis but not antisera to other commonly isolated mycobacteria. Rabbits immunized with the recombinant 35K protein produced antisera which bound to both the 35K and 53K protein bands, a single 35K protein band present in a culture filtrate of M. tuberculosis, and single protein bands with differing molecular weights in whole cell homogenates from other Mycobacterium spp. An additional recombinant vector containing a 2.2-kb subclone of the 4.7-kb sequence was constructed and, when used as a probe, demonstrated homology with various fragments of chromosomal digests of selected mycobacteria. Reactivity of this probe to Mycobacterium bovis and M. bovis BCG was indistinguishable from reactivity to M. tuberculosis. Immunoglobulin G reactivity to the 35K antigen was detected in antisera from 8 of 20 persons with active tuberculosis, 4 of 18 persons with leprosy, and none of 14 healthy controls. In contrast, reactivity to various proteins in M. tuberculosis culture filtrate was present in 18 of 20 patients with tuberculosis, 16 to 18 patients with leprosy, and 5 of 14 controls. The production of M. tuberculosis proteins by E. coli circumvents many difficulties encountered in the growth and manipulation of M. tuberculosis and may facilitate the development of better diagnostic and immunizing reagents. PMID- 3112177 TI - Effect of acidity and antimicrobial agent-like compounds on viability of Plesiomonas shigelloides. AB - Nineteen Plesiomonas shigelloides strains were evaluated for their stability at acidic and slightly alkaline pHs and for their susceptibility to antimicrobial agent-like compounds produced by enteric flora. Most P. shigelloides isolates were rapidly inactivated under high-acid (pH 4 or less) conditions. Screening of enteric bacteria for elaboration of factors active against P. shigelloides revealed two organisms (Pseudomonas aeruginosa and Streptococcus [Enterococcus] faecium) capable of secreting such inhibitory substances. The results of this study suggest some factors potentially important in regulating gastrointestinal colonization by P. shigelloides from environmental sources. PMID- 3112178 TI - Isolation of Clostridium difficile and detection of cytotoxin in the feces of diarrheic foals in the absence of antimicrobial treatment. AB - Clostridium difficile was isolated from the feces of 27 of 43 diarrheic foals (63%), and cytotoxin was detected in feces from 28 diarrheic foals (65%). The foals had not received any antimicrobial treatment before the onset of diarrhea. C. difficile was not isolated from feces of 18 normal foals without diarrhea and 62 adult horses (P less than 0.005). This finding of C. difficile and its toxins in association with diarrhea in foals adds another possible cause to the list of infectious agents which may cause diarrhea in foals. PMID- 3112179 TI - Ultrafiltration to reject human interleukin-1-inducing substances derived from bacterial cultures. AB - Interleukin-1 (IL-1), a polypeptide cytokine, is an important mediator of host responses to infection and injury. Picogram per milliliter concentrations of bacterial products (endo- or exotoxins) stimulate human monocytes to produce IL-1 in vitro. The design of this study was based on the clinical model of bacterial contamination of fluid intended to be directly injected into humans. Physiologic saline contaminated with bacterial toxins was passed through a hollow fiber ultrafilter, and the ultrafiltrates were tested for their ability to induce human IL-1 production. The ultrafiltrates were added directly to freshly obtained human blood mononuclear cells, and after 24 h of incubation the supernatant media were assayed for the presence of IL-1. The results indicate that the IL-1-inducing material(s) present in bacterial cultures of gram-negative organisms is rejected by a factor of 100 to 100,000 by molecular size exclusion and by absorption; rejection is sustained for at least 32 liters of fluid; the rejection of Limulus reactive material by the ultrafilter is greater for purified endotoxin than for native endotoxins derived from live bacterial cultures; and nonendotoxin IL-1 inducing toxins (molecular weight, 24,000) from Staphylococcus aureus are not rejected or absorbed. These results demonstrate that there is a considerable margin of safety with the ultrafiltration method and that it can be applied to clinical situations. PMID- 3112180 TI - Whole chromosomal DNA probes for rapid identification of Mycobacterium tuberculosis and Mycobacterium avium complex. AB - Whole chromosomal DNA probes were used to identify clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium complex, and Mycobacterium gordonae. The probe for M. tuberculosis was prepared from Mycobacterium bovis BCG, which has been shown to be closely related to M. tuberculosis. A probe for the M. avium complex was prepared from three strains representing each of the three DNA homology groups in the M. avium complex. The probes were used in dot blot assays to identify clinical isolates of mycobacteria. The dot blot test correctly identified 57 of the 61 (93%) cultures grown on solid media, and 100% of antibiotic-treated broth-grown cells were correctly identified. Identification by dot blot required a maximum of 48 h. When the probes were tested against 63 positive BACTEC (Johnston Laboratories, Inc., Towson, Md.) cultures of clinical specimens, 59% were correctly identified. However, of the 14 BACTEC cultures that had been treated with antibiotics before being lysed, 13 (93%) were correctly identified. PMID- 3112181 TI - Double-antibody sandwich enzyme-linked immunosorbent assay for rapid detection of toxin-producing Corynebacterium diphtheriae. AB - An enzyme-linked immunosorbent assay for determining the toxigenicity of Corynebacterium diphtheriae is presented. The assay uses hyperimmune horse diphtheria antitoxin as a capture antibody and mouse monoclonal diphtheria antitoxin as a detecting antibody. Growth of bacteria and capture of diphtheria toxin by antitoxin are carried out in one step. Toxin produced by as little as 100 toxin-producing corynebacteria is detectable, corresponding to a sensitivity of 10 ng of diphtheria toxin per ml. Demonstration of toxin after incubation of the bacteria for 4.75 h, as well as after 18 h, was in accordance with the modified Elek gel diffusion method and the guinea pig inoculation test. However, heavy inocula incubated overnight produced significantly lower optical density than did diluted inocula; thus, the higher optical density was used as an indicator of toxin production. A decrease in optical density was also seen by shortening the incubation time. For laboratory safety, ethanol was added to the microtiter plate wells before washing out of the bacteria. This resulted in a further decrease in optical density. Using 4.75-h incubation time gave a single false-negative result. No false-positive results were ever seen. Incubation for 18 h is suitable for large-scale screening, and 4.75 h of incubation is suitable for rapid identification of toxin-producing C. diphtheriae. PMID- 3112182 TI - Simultaneous production of rhamnolipids, 2-alkyl-4-hydroxyquinolines, and phenazines by clinical isolates of Pseudomonas aeruginosa. AB - Of 72 clinical isolates of Pseudomonas aeruginosa examined for simultaneous production of secondary metabolites, 86% produced 2-alkyl-4-hydroxyquinolines, 75% produced rhamnolipids, and 58% produced phenazines, including pyocyanin. Whereas isolates producing two or one constituted smaller groups, 39% released all three metabolites. Metabolite production did not appear to influence site of infection. PMID- 3112183 TI - Sex steroid hormone regulation of follicle-stimulating hormone subunit messenger ribonucleic acid (mRNA) levels in the rat. AB - Follicle-stimulating hormone (FSH) beta, luteinizing hormone (LH) beta, and alpha subunit messenger RNA (mRNA) levels were examined in rats after castration and sex-steroid replacement. Subunit mRNAs were determined by blot hybridization using rat FSH beta genomic DNA, and alpha and LH beta complementary DNA (cDNA). Rat FSH beta mRNA is 1.7 kilobase in size. After ovariectomy, female FSH beta mRNA levels increased fourfold, whereas those of LH beta and alpha increased twenty- and eightfold, respectively. With estradiol, all subunits returned toward normal levels. Male LH beta and alpha mRNA levels rose eight- and fourfold, respectively, 40 d postcastration, but FSH beta mRNA levels increased minimally. After 7 d of testosterone propionate, LH beta and alpha mRNAs declined to normal levels, whereas FSH beta mRNA increased slightly. We conclude that in female rats FSH beta is negatively regulated by gonadal steroids, but to a lesser extent than LH beta or alpha mRNAs, and there is a differential regulation of FSH beta mRNA levels in males as compared with females at the time points examined. PMID- 3112184 TI - B lymphocyte reconstitution after human bone marrow transplantation. Leu-1 antigen defines a distinct population of B lymphocytes. AB - Differences in the expression of Leu-1 (CD5) define two populations of recovering B cells after human marrow transplantation, Leu-1+ and Leu-1- B cells. The Leu-1+ B cells were polyclonal, of donor origin, and did not express detectable interleukin 2 receptor. Leu-1+ B cells generally appeared 2-4 wk after marrow grafting and often preceded the recovery of Leu-1- B cells. Acute and chronic graft vs. host disease (GvHD) resulted in the recovery of significantly fewer Leu 1+ B cells, whereas Leu-1- B cells were only decreased in acute GvHD. Multivariate analysis showed no significant effect of age, disease, prednisone or azathioprine, or ex vivo treatment of the marrow with anti-Leu-1 and complement on recovery of Leu-1+ and Leu-1- B cells, independent of the effects of GvHD. Leu 1+ B cells are a major lymphocyte population posttransplant. They may reflect a stage of differentiation of normal B cells or a separate B cell lineage. PMID- 3112185 TI - Renal bicarbonate reabsorption in the rat. II. Distal tubule load dependence and effect of hypokalemia. AB - We studied two groups of rats acutely loaded with bicarbonate, control rats on a standard diet and rats kept on a K-free diet for 3 wk. Compared with controls, K depleted rats had reduced fractional excretion of bicarbonate despite their elevated filtered bicarbonate load. Distal bicarbonate reabsorption increased in K-depleted rats. In the presence of almost identical early distal bicarbonate loads (481 +/- 40 pmol/min in controls and 444 +/- 50 pmol/min in K depletion), distal bicarbonate reabsorption was significantly enhanced in K depletion (247 +/ 17 pmol/min) as compared with controls (179 +/- 18 pmol/min). These values are significantly different from each other, and both are severalfold higher than bicarbonate reabsorption in nonloaded conditions. In conclusion, distal bicarbonate reabsorption is load dependent, and distal bicarbonate reabsorption is stimulated in K depletion. PMID- 3112187 TI - Aplastic crisis in haemolytic anemias not associated with human parvovirus infection. PMID- 3112186 TI - Role of serum carrier proteins in the peripheral metabolism and tissue distribution of thyroid hormones in familial dysalbuminemic hyperthyroxinemia and congenital elevation of thyroxine-binding globulin. AB - To investigate the role of thyroxine-binding globulin (TBG) and albumin in the availability of thyroid hormones to peripheral tissues, comprehensive kinetic studies of thyroxine (T4) and triiodothyronine (T3) were carried out in eight subjects with familial dysalbuminemic hyperthyroxinemia (FDH), in four subjects with inherited TBG excess, and in 15 normals. In high-TBG subjects, the reduction of T4 and T3 plasma clearance rates (by 51% and 54%, respectively) was associated with normal daily productions; T4 and T3 distribution volumes were significantly reduced. In FDH subjects T4 clearance was less reduced (by 31%) than in high TBG; consequently T4 production rate was significantly increased (by 42%); T4 and T3 distribution volumes and T3 clearance rate were unchanged. Increased T3 peripheral production in FDH (by 24%) indicates that T4 bound to abnormal albumin is more available to tissues than T4 carried by TBG, thus suggesting an important role of albumin in T4 availability to the periphery. PMID- 3112188 TI - Initial junctions between developing parallel fibers and Purkinje cells are different from mature synaptic junctions. AB - During postnatal development of cerebellar cortex, junctions are formed between parallel fiber axons and the shafts of Purkinje cell dendrites. These shaft junctions resemble synaptic junctions on spines in thin sections, in that the axon contains a cluster of synaptic vesicles, and the pre- and postjunctional membranes are lined by electron-dense material. The shaft junctions do not have the aggregate of particles arrayed on the extracellular half of the postjunctional membrane that is characteristic of mature spine synaptic junctions in freeze-fractured preparations, however, and so presumably have a different protein composition. Shaft junctions are transient specializations, present only in developing tissue, but do not appear simply to be intermediates in the formation of mature spine synaptic junctions. In normal development, spines are formed by the Purkinje cell dendrite at sites not occupied by shaft junctions. Moreover, in certain neurological mutant mice, shaft junctions form in the absence of spine synapses, and in other systems spines develop in the absence of shaft junctions. We suggest that shaft junctions are a class of synapse formed during development which is distinguished by its capacity to dissociate, and that only some fraction of the parallel fibers forming shaft synapses with a developing Purkinje cell will have established spine synapses in the adult. PMID- 3112189 TI - Corneal sensory pathway in the rat: a horseradish peroxidase tracing study. AB - The methods of transganglionic transport of horseradish peroxidase (HRP) and horseradish peroxidase--wheat germ agglutinin (HRP-WGA) were used to determine the location within the trigeminal ganglion of the primary afferent neurons that innervate the rat central cornea, and the brainstem and spinal cord termination sites of these cells. In each of 18 animals, solutions of HRP or HRP-WGA were applied to the scarified corneal surface and allowed to infiltrate into the corneal epithelium and stroma for 15 minutes. Postmortem examination of the corneal whole mounts from the experimental animals, and of corneas and neural tissues from several control animals, showed that the HRP/HRP-WGA remained confined to the central cornea with no spread into adjacent intra- or extraorbital tissues. HRP-labeled corneal afferent somata were located in the dorsal part of the ophthalmic region of the ipsilateral trigeminal ganglion. The central fibers of the corneal afferent neurons projected very heavily to interstitial nuclei of Cajal in the spinal tract of V at the level of caudal pars interpolaris and rostral pars caudalis, lightly to the pars caudalis/C1 transition zone, and sparsely to the dorsal horn of spinal cord segments C1-C3. The trigeminal main sensory nucleus, pars oralis, the rostral three-fourths of pars interpolaris, and an extensive midregion of pars caudalis were totally devoid of reaction product. Terminal fields in caudal pars caudalis and in the spinal cord dorsal horn were concentrated largely in the outer half of lamina II, with lesser accumulations in lamina I, the deeper half of lamina II, and in lamina III. The present study demonstrates for the first time by means of an anatomical tracing procedure the brainstem termination sites of corneal afferent neurons in the rat. The patchy, discontinuous nature of the corneal afferent projection to the caudal trigeminal brainstem nuclear complex (TBNC), and the total lack of corneal projections to rostral subdivisions of the TBNC, provide an exception to the general rule of trigeminal organization in which most areas of the head and face are represented as continuous columns throughout the rostrocaudal extent of the ipsilateral TBNC. PMID- 3112190 TI - Changing nursing practice through continuing education in physical assessment: perceived barriers to implementation. PMID- 3112191 TI - Learning needs are dynamic: the value of repeated assessment. PMID- 3112192 TI - Characteristics of RN students continuing their education in a BS program. PMID- 3112194 TI - Who should control continuing education for nursing? PMID- 3112193 TI - A theoretical model based on evaluation theories and application to continuing education programs in nursing. PMID- 3112196 TI - The focus group or let's give them what they want. PMID- 3112195 TI - Evaluation of a clinical preceptor program for new graduates--eight years later. PMID- 3112197 TI - Notes on CE. Business success. PMID- 3112198 TI - Using computers in administering a continuing education program. PMID- 3112200 TI - In vitro modulation of T6 expression on gingival Langerhans cells by interleukin 1 inhibitors and ETAF. AB - T6 antigen is a highly specific marker for human Langerhans cells (LC). Previous studies have demonstrated that Interleukin-1 (IL-1) and an IL-1 inhibitor (ILS) modulate LC T6 expression (T6E) in explant culture. The present study examined the in vitro modulation of T6E by two molecules: epidermal-cell-derived thymocyte activating factor (ETAF), and a bone-derived protein (BP) implicated in the control of bone homeostasis. The effect of purified ILS was also examined. ETAF mimicked the stimulatory effect of IL-1 on LC T6E, while BP depressed T6E in a manner resembling that seen with ILS. No agents altered Class II (DR and DQ) expression by LC. BP was a specific IL-1 inhibitor, and did not inhibit thymocyte proliferation in the standard IL-1 bioassay in the absence of IL-1. These results demonstrate that molecules resembling IL-1 or ILS can modulate T6E, and implicate locally produced ETAF and ILS in the regulation of T6E in the oral mucosa in vivo. PMID- 3112201 TI - Antimicrobial action of new, proprietary lining cements. AB - The antibacterial activity of innovative, commercial lining cements was investigated. A liner which contains calcium hydroxide and is polymerized by visible light (Prisma VLC Dycal) and a glass-ionomer lining cement (GC lining cement) were compared with two more established lining cements (Advanced Formula II Dycal and Life). Antibacterial activity and hemolysis-like agar change at 24, 48, and 72 hours were measured on blood agar plates inoculated with Streptococcus mutans KPSK 2 (serotype c), Lactobacillus casei ssp rhamnosus ATCC 11981, and chewing-stimulated saliva. Prisma VLC Dycal did not affect bacteria or agar. The glass-ionomer lining cement, with an acidic pH at setting, had the most pronounced effect on all test organisms and on the agar. Even after 48 hours' setting, it inhibited growth of S. mutans. The control lining cement (AFII Dycal) showed antibacterial activity toward both specific micro-organisms as well as some activity against the salivary organisms. The material Life showed only partial inhibition of microbial growth. For all lining cements, the hemolytic like agar change correlated with antibacterial effects. The surface pH of the freshly-set cements containing calcium hydroxide was alkaline. It would seem that a simple correlation between high surface pH and antibacterial activity among these cements does not exist. Also, further biological characterization of new lining cements is required to direct their appropriate clinical use. PMID- 3112199 TI - Calcium alginate-immobilized cultures of lactic Streptococci are protected from bacteriophages. AB - Calcium alginate-immobilized cultures of lactic streptococci were grown in milk and assessed for their sensitivity to homologous bacteriophage, proteolytic activity, and acid production. Immobilized cultures of Streptococcus lactis C2 and Streptococcus cremoris HP were protected from attack by bacteriophage due to the exclusion of phage particles from the gel matrix. These cultures were also functionally proteinase-deficient when immobilized in calcium alginate beads and grown in milk. Acid was produced by immobilized cultures at a lower rate than cells freely suspended in milk due in part to the inability of the immobilized cells to hydrolyze milk proteins. Agitation of immobilized cultures slightly increased acid production, suggesting that diffusional limitations of substrate into the beads contributed to decreased acid production. Use of immobilized cultures of lactic streptococci in certain dairy fermentations may be advantageous due to the protection of these cultures from attack by virulent bacteriophage. PMID- 3112202 TI - Antigenic heterogeneity of non-pigmented Bacteroides species isolated from the human oral cavity. AB - Serological studies on 27 strains of non-pigmented Bacteroides isolated from the human oral cavity revealed multiple serotypes within B. buccae. B. capillus (= B. buccae) and B. pentosaceus (= B. buccae) were found to be serogroups within B. buccae. B. denticola possessed cross-reactive antigens with B. buccae. Tested strains of B. oralis, B. veroralis, B. oris, and B. heparinolyticus were clearly differentiated from each other. PMID- 3112203 TI - PCB and PCQ concentrations in subcutaneous tissue from patients with PCB poisoning (yusho). PMID- 3112204 TI - Primary osteoma cutis. PMID- 3112205 TI - Eosinophil chemotactic activity of beta-galactosidase. PMID- 3112206 TI - Disputed pocket elimination. PMID- 3112207 TI - Retention and effectiveness of a single application of white sealant after 10 years. AB - This retrospective cohort study assesses the caries prevalence, cost effectiveness, and retention of pit and fissure sealant in children living in a fluoridated area 10 years after the single application of a colored sealant to permanent first molars. The status of the sealant and presence of caries or restorations on the sealed teeth was assessed. An age-, gender-, and residence matched control group of children was examined and similar data were collected for comparison with the sealed group. The cost of a single surface restoration is compared with the cost of sealant application. PMID- 3112208 TI - Postoperative enteral hyperalimentation for cryptosporidial acute cholecystitis associated with AIDS and enteritis. AB - A homosexual youth presented with undiagnosed acute cryptosporidial cholecystitis, a fever of 102.8 degrees F and a WBC of 3500/mm3. This was preceded by several months of watery diarrhea and 20% weight loss. Following cholecystectomy, G-I function was maintained by efficient esophageal aspiration of swallowed air, with simultaneous immediate duodenal feeding of elemental diet. He absorbed 160 g amino acids and 4200 kcal, and was safely self-sufficient when discharged 26 hours postoperatively. Reappearance of the persistent cryptosporidial enteritis was followed by diagnoses of the offending organism and the associated AIDS. He failed to respond to specific spiramycin therapy, and 8 months after cholecystectomy he succumbed to pneumocystis carinii pneumonia. For this malnourished and particularly vulnerable patient, preservation of postoperative G-I function and its exploitation for enteral support may have been essential to enhance "immune competence" and lead to a remarkably smooth and rapid recovery. PMID- 3112209 TI - Identifying the older person likely to require long-term care services. AB - The purpose of this study is to determine the accuracy of predictions in identifying older persons who subsequently require long-term care such as home services or institutionalization. Eighty-six individuals undergoing geriatric evaluation between May 1983 and April 1984 were evaluated using a series of commonplace tasks such as opening doors, stacking checkers, and copying a simple sentence. Predictions of an individual's use of long-term care services were made during the initial evaluation and were based on whether the person could complete all the manual tasks and on the amount of time required to do so. Outcomes were determined by telephone interviews by a trained social worker in Dec 1984. A statistically significant association (P less than 0.005) was observed between the predictions and actual outcomes. Analysis of variance confirmed that the mean times for each outcome were different (F = 2.6, P less than 0.05). The results suggest that timing manual performance offers a useful way to prospectively identify older persons at risk of requiring additional long-term care services. PMID- 3112210 TI - Brain tumors presenting as a seizure disorder in infants. AB - Seizures occur in 25% to 40% of children with supratentorial tumors and are the presenting complaint in 10% to 15%. However, when divided by age, only 2% of children with seizures as the presenting complaint of brain tumors were less than 1 year of age. Three children, ranging in age from 20 days to 7 months and seen within the past 2 years, form the basis of this report. The presenting complaint in all children was seizures. Computed tomographic (CT) scan was indicated in all children because of intractability to anticonvulsant drug therapy (one patient) and focal electroencephalographic (EEG) abnormality with clinical evidence of complex partial seizure activity (two patients). CT scan showed a contrast enhancing mass in the medial temporal lobe in all patients. At surgery, a temporal lobe tumor was found and resected in all children. Histopathologic examination revealed a ganglioglioma, a fibrillary astrocytoma, and an anaplastic astrocytoma. All children did well postoperatively and are seizure free to date. Our experience suggests that supratentorial tumors should be considered as a cause of intractable and/or focal seizures in children under 1 year of age, and that such tumors should be attacked aggressively neurosurgically. Our experience is also in agreement with that of Tadmor et al, who have suggested that with the advent of CT scanning supratentorial tumors in this age group have been found to be more common than previously realized. PMID- 3112211 TI - Midline foci of epileptiform activity in children and neonates. AB - We report the clinical and electroencephalographic (EEG) correlates of focal potentially epileptogenic discharge arising from midline sagittal vertices (Fz, Cz, Pz) in 21 children prospectively identified from among 7,051 consecutive EEGs recorded during a 27-month period. The patients range in age from neonates to 13 years. EEGs were obtained during evaluations for solitary or recurrent seizures (17/21), attention deficit disorder (2/21), psychomotor retardation (1/21), and headache (1/21). Clinical seizure types were diverse and included simple partial (5/17), complex partial (2/17), generalized tonic-clonic (4/17), mixed (2/17), and neonatal (4/17). The majority (13/21) of patients had an identifiable etiology for their disorder; CT scans verified mass lesions in two patients. Midline epileptogenic foci were present during wakefulness in 14 of 17 older children and restricted to sleep in the others. Sleep states were indeterminate in the four neonates. Midline foci were exquisitely confined to Fz, Cz, and/or Pz in 6 of 17 older children and would have been entirely missed by a recording montage that did not include vertex electrodes. In five other children, midline foci spread preferentially to the adjacent central-parietal regions and closely resembled the appearance of benign rolandic foci in the longitudinal EEG montages, a potentially serious cause of EEG misinterpretation in view of the high incidence of neuropathology in this patient group. PMID- 3112212 TI - Efficacy of valproic acid in the treatment of Sydenham's chorea. PMID- 3112214 TI - Ischemic pancreatitis and hepatitis secondary to ergotamine poisoning. AB - Acute ergotamine intoxication in a 29-year-old man was complicated by peripheral ischemia, pancreatitis, and hepatitis. The patient was treated with sodium nitroprusside infusion. Complications and treatment of ergotamine poisoning are discussed. PMID- 3112213 TI - Umbilical cord compression produces pulmonary hypertension in newborn lambs: a model to study the pathophysiology of persistent pulmonary hypertension in the newborn. AB - We investigated the effects of chronic intrauterine hypoxaemia produced by prolonged partial umbilical cord compression on the circulation shortly after birth in lambs. Vascular catheters were inserted in 10 fetal sheep at 120 to 130 days gestation to measure descending aortic blood gases, arterial pH, and arterial O2 saturation. An inflatable silicone rubber balloon cuff was also placed around the umbilical cord. After recovery and the return of descending aortic blood gases to the normal range, the balloon was gradually inflated, decreasing the PaO2 from 21.2 +/- 3.6 to 17.5 +/- 1.3 mm Hg and the arterial O2 saturation from 57.1 +/- 9.2% to 37.2% +/- 5.2. After 14.3 +/- 3.7 days of partial umbilical cord compression, the lambs were delivered by Caesarean section, instrumented to measure systemic and pulmonary arterial, right atrial and pulmonary arterial wedge pressures, pulmonary and systemic blood flows, and mechanically ventilated. Five normal lambs were also studied. From 60 to 120 min after delivery, when compared to normal lambs, the umbilical compression lambs had an increased pulmonary arterial pressure (P less than 0.05) pulmonary vascular resistance (P less than 0.05), and right atrial pressure (P less than 0.05) with similar arterial blood gases. In both groups, hypoxic ventilation produced an increase in pulmonary arterial pressure (P less than 0.05) which on return to room air ventilation decreased to baseline in the normal lambs but not in the umbilical cord compression lambs (P less than 0.05). Prolonged partial umbilical cord compression produces chronic fetal hypoxaemia and pulmonary arterial hypertension after birth. This may represent a model to study the pathophysiology of persistent pulmonary hypertension syndrome. PMID- 3112215 TI - Diagnostic Mr 31,000 Schistosoma mansoni proteins: requirement of infection, but not immunization, and use of the "miniblot" technique for the production of monoclonal antibodies. AB - Antibodies directed against diagnostic Mr 31,000 polypeptide(s) of adult Schistosoma mansoni were already formed in mice during prepatency. In contrast, repeated immunization of mice with homogenates of adult schistosomes failed to elicit antibodies detectable in immunoblots in the Mr 31,000 region. Therefore, spleen cells of infected mice were used to produce hybridoma lines. The "miniblot technique" was developed in order to detect in hybridoma supernatants antibodies against schistosome Mr 31,000 components. Electrophoretically separated total S. mansoni proteins were transferred onto nitrocellulose, and the position of the Mr 31,000 components was determined with polyclonal antisera and immunoblotting. Pieces of about 3 square mm of nitrocellulose bearing the diagnostic proteins were incubated with about 100 microliter of hybridoma supernatant in microtitre plates and subsequently probed with peroxidase-conjugated antibody to mouse IgG. This screening technique identified hybridomas secreting antibody to the relevant S. mansoni antigens. It is applicable to other defined parasite antigens, which are, however, not available in biochemically purified form. The monoclonal antibodies produced against the proteins with diagnostic potential reacted with antigens localized in the schistosome gut. PMID- 3112216 TI - The Wilhelmine E. Key 1986 invitational lecture. Fifty years of genetic load. AB - The author's involvement with and his successive reactions to the genetic load concept [whose beginning is identified with Haldane's paper. The effect of variation on fitness] is presented in the form of a personal odyssey. The major change in attitude involved the realization that the density- and frequency independent selection discussed by most population geneticists has little bearing on events transpiring within natural populations; instead, natural selection should be viewed primarily as a density- and frequency-dependent phenomenon. Under this view, the culling of a large number of young zygotes to the considerably smaller number of adults that can be sustained by the environment is an essential process enabling any population's continued existence; to the extent that genetic variation facilitates culling, a genetic load (in direct opposition to the early view) can enhance a population's persistence through time. PMID- 3112217 TI - Ijanikin: a study of environmental health in a rural Nigerian community. AB - Ijanikin is a typical Yoruba village in the rain forest belt area of Southern Nigeria. The childhood years in this community are fraught with the danger of numerous communicable diseases, compounded by inadequate supply of good quality foods to meet normal requirements and allow a margin of safety for the stress of infections. Overcrowding and poor ventilation in the houses are important factors in the spread of communicable diseases, while poor sanitation and deficient personal hygiene account for the heavy burden of intestinal parasitoses. Improvement in the health of this and other similar rural communities would require the provision of clean water supply, installation of essential sanitary facilities, provision of adequate food supply, and a well-planned and carefully executed health education programme. PMID- 3112218 TI - Comparative activation requirements of human peripheral blood, spleen, and lymph node B cells. AB - Human peripheral blood, spleen, and lymph node B cells were stimulated with Cowan I Staphylococcus aureus (SA) or F(ab')2 fragments of anti-mu antibody (anti-mu) and various lymphokines and were analyzed for proliferation and generation of Ig secreting cells (ISC). SA alone but not anti-mu stimulated minimal proliferation of each population. Recombinant IL 2 (r-IL 2) effectively promoted proliferation of SA-stimulated blood and spleen B cells, but supported less vigorous responses of lymph node B cells. By contrast, r-IL 2 enhanced DNA synthesis of all anti-mu stimulated B cells early in culture, but did not promote sustained proliferation of anti-mu-stimulated lymph node B cells and only promoted ongoing DNA synthesis of some anti-mu-activated blood (eight out of 17) and spleen (five out of 14) B cell preparations. Recombinant interferon-gamma (r-IFN-gamma) and a commercial preparation of B cell growth factor (BCGF) also augmented DNA synthesis of all three B cell populations stimulated with SA or anti-mu early in culture, but neither alone was able to sustain maximal proliferation. Markedly enhanced sustained proliferation of all three anti-mu- and SA-stimulated B cell populations was noted when cultures were supported by the combination of r-IL 2 and BCGF, or to a lesser extent by r-IL 2 and r-IFN-gamma. The generation of ISC from SA-stimulated blood or spleen but not lymph node B cells was effectively supported by r-IL 2 alone. Differentiation of lymph node B cells required the combination of r-IL 2 and BCGF. These studies emphasize the importance of both the activation stimulus and the origin of the B cells in determining the lymphokine requirements of human B cell responsiveness. PMID- 3112219 TI - T cell antigen receptor triggered exocytosis in cytotoxic T lymphocytes is inhibited by soluble, but not immobilized monoclonal antibodies to Lyt-2 antigen. AB - The effect of monoclonal antibodies (mAb) to surface antigens on the T cell antigen receptor (TcR)-triggered exocytosis of intracellular granules in cytotoxic T lymphocytes (CTL) was studied. Soluble anti-LFA-1, anti-TcR, and anti Lyt-2 mAb inhibited both CTL-inflicted 51Cr-release from the target cell (TC) and TC-stimulated exocytosis of granules from cloned CTL. Soluble anti-TcR and anti Lyt-2 mAb but not soluble anti-LFA-1 mAb inhibited exocytosis, which was triggered by solid-phase anti-TcR mAb. Immobilized anti-Lyt-2 did not inhibit secretion triggered by immobilized anti-TcR mAb; immobilized anti-LFA-1 mAb had an modest inhibiting effect. Inhibition of exocytosis by soluble anti-Lyt-2 mAb was greater when stimulating anti-TcR mAb were immobilized at a lower density on a plastic surface. When the requirement for TcR cross-linking was bypassed by synergistic action of phorbol ester and ionophore A23187, no inhibition of exocytosis by soluble anti-Lyt-2 mAb was detected. The obtained data point to steric hindrance as the most likely explanation of the inhibition of TcR triggered CTL activation by anti-Lyt-2 mAb. PMID- 3112220 TI - Genetic influence on the levels of circulating CD5 B lymphocytes. AB - By using sensitive two- and three-color immunofluorescence analyses, we readily detect CD5B cells (Leu 1 B cells) in the peripheral blood of normal adults. These circulating CD5 B lymphocytes coexpress B cell differentiation antigens CD20, CD21, CD19, sIgM and sIgD, and HLA-DR. Unlike CD5-negative B cells from most adults, however, these cells co-express CD11, a finding also noted for malignant CD5 B cells from several patients with CLL. Between normal volunteers, there exists heterogeneity in the proportion of PBL that co-express CD5 and B cell surface antigens, such cells representing between 0 and 6% of peripheral lymphocytes. Despite such heterogeneity between unrelated individuals, analyses of repeated blood samples from the same person reveal that the proportions of CD5 B lymphocytes are constant over time. Examination of blood samples from related family members, monozygotic twins, and triplets indicate that the relative proportion of circulating CD5 B cells may be genetically regulated. This is apparent even for monozygotic twins discordant for rheumatoid arthritis. Four sets of such twins are examined, each set having one individual with clinically active, seropositive rheumatoid arthritis and another without detectable rheumatoid factor or clinical pathology. Despite such noted differences, twins from each set share identical proportions of circulating CD5 B cells. In summary, our studies indicate that the level of CD5 B lymphocytes is a rather stable phenotypic trait that is under genetic control. PMID- 3112221 TI - Identification and isolation of a T4+T8+ cell with high T3 expression in human thymus: a possible late intermediate in thymocyte differentiation. AB - By using sensitive three-color fluorescence flow cytometric techniques, we were able to identify a T4+T8+ thymocyte with high T3 surface density (T3H) representing 4 to 9% of thymocytes. To characterize the T3HT4+T8+ cell, thymic subpopulations with high T3 surface density (T3H) and lower T3 density (T3L/T3-) were compared with regard to T6 expression. The T3H subpopulation was characterized by lower numbers of T6+ cells and reduced levels of T6 antigen density, whereas the T3L/T3- population was greater than 90% T6+ and expressed this antigen at high cell surface density. In addition, T3H fractions appeared to possess higher levels of nuclear activation with respect to the T3L/T3- population as indicated by increased log 90 degrees scatter profiles. These results suggest that thymocytes with high T3 surface expression are not only more differentiated, but also more activated than the majority of the thymic population. The T3HT4+T8+ fraction could be distinguished from T4+T8+ thymocytes with lower T3 density not only by an increased log 90 degrees scatter profile, but also by the presence of T4+T8+ cells with reduced levels of T8 surface antigen. Our results indicate that T4+T8+ thymocytes with high T3 surface density are a distinct subpopulation and may represent the immediate precursors of the phenotypically more mature T3HT4+T8- and T3HT8+T4- subpopulations found in human thymus. PMID- 3112222 TI - Impaired expression of high affinity interleukin 2 receptor on activated lymphocytes from patients with systemic lupus erythematosus. AB - Peripheral lymphocytes stimulated with phytohemagglutinin (PHA-blasts) were examined for their responsiveness to exogenous interleukin 2 (IL-2). The proliferative response of PHA-blasts to IL-2 was significantly lower in patients with systemic lupus erythematosus (SLE) than in normal subjects. To clarify the reason for this defect, the expression of IL-2 receptor (IL-2R) on PHA-blasts was investigated using anti-Tac antibody and purified IL-2. Cytofluorometric analysis showed no statistical differences in the Tac positivity of PHA-blasts among normal subjects and patients with active and inactive SLE. Scatchard analysis using 125I-labeled anti-Tac monoclonal antibody revealed that the number of Tac epitopes on PHA-blasts was also not different among them. Next, the affinity of IL-2R expressed on PHA-blasts was determined by Scatchard analysis using radiolabeled IL-2 as a ligand. The number of high affinity IL-2R on the PHA blasts was significantly decreased in patients with active and inactive SLE, as compared with normal subjects. The responsiveness of PHA-blasts to exogenous IL-2 was well correlated to the number of high affinity IL-2R, but not to the number of Tac epitopes or total IL-2R. Inasmuch as high affinity components of IL-2R are functionally active, the defective expression of high affinity IL-2R may be responsible for the T cell dysfunctions in SLE. PMID- 3112223 TI - A T cell-independent mechanism of macrophage activation by interferon-gamma. AB - A primary interest in immunity to intracellular pathogenic microorganisms and tumors is to understand the mechanisms by which macrophages are activated for various functions. Two parameters of macrophage activation are the expression of the class II histocompatibility proteins or Ia molecules (1), and cytotoxic activity. The ability of T cells to induce these responses has been extensively documented and occurs via their secretion of interferon-gamma (IFN-gamma) after interaction with antigen (2-6). However, in a recent study using mice with the severe combined immunodeficiency (scid) mutation (7) which have no detectable T or B cell functions (7-9), we were surprised to find the induction of Ia expression on macrophages and the partial inhibition of bacterial growth after infection with Listeria monocytogenes (10). We have now utilized neutralizing monoclonal antibodies specific for murine IFN-gamma to investigate the mechanism of macrophage activation in scid mice. We show here that IFN-gamma can be produced by scid mice in the absence of lymphocyte-mediated immunity, and this IFN-gamma is important for macrophage activation during infection with Listeria. These results indicate the presence of an important T lymphocyte-independent mechanism of macrophage activation and IFN-gamma production in response to infection. PMID- 3112224 TI - The differential inhibition of hemopoietic growth factor activity by cytotoxins and interferon-gamma. AB - The effects of recombinant human tumor necrosis factor (TNF), lymphotoxin (LT), and interferon-gamma (IFN-gamma) on the growth of human hemopoietic progenitor cells in clonal culture have been examined. Colony growth was induced by using granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage colony stimulating factor (GM-CSF). A suppressive effect of TNF, LT, and IFN-gamma on the development of granulocyte, macrophage, and mixed granulocyte/macrophage colonies was shown. Suppression of colonies formed after stimulation with G-CSF was greater than that observed after stimulation with GM-CSF. In the presence of a monoclonal antibody to TNF, or polyclonal antibodies to either LT or IFN-gamma, the inhibitory effect of the molecule to which the antibody was directed was abrogated. These findings suggest that progenitor cells responsive to G-CSF or GM CSF have different sensitivities to the effects of TNF, LT, and IFN-gamma. Defining the interactions of growth factors and inhibitors should increase understanding of mechanisms underlying diseases associated with suppression of normal hemopoiesis, and in predicting the effects in vivo of these bioregulatory molecules in clinical medicine. PMID- 3112225 TI - B cell growth-promoting activity of recombinant human interleukin 4. AB - Human interleukin 4 (IL-4), also known as B cell stimulatory factor 1, is a T cell-derived glycoprotein consisting of 129 amino acids for which a cDNA has been recently isolated. IL-4 displays little or no B cell growth factor (BCGF) activity in the standard anti-IgM costimulatory assay using suboptimal concentrations of soluble anti-IgM antibody whereas the low m.w. BCGF is very active. When insolubilized anti-IgM was used as the costimulating agent, both IL 4 and the low m.w. BCGF were found to promote B cell proliferation. Human IL-4 is able to induce the proliferation of B lymphocytes preactivated for either 1 day with insolubilized anti-IgM antibody or for 3 days with Staphylococcus aureus strain Cowan I. However, IL-4 is poorly mitogenic for B cells preactivated for 1 day with the Staphylococcus strain whereas the low m.w. BCGF strongly enhances the proliferation of these B cells. These two findings demonstrate that the preactivation signal necessary to induce human B cells to proliferate in response to IL-4 is critical. The increased tritiated thymidine ([3H]dThd) uptake in preactivated B cell cultures with IL-4 reflects cel proliferation because cell cycle analysis demonstrates that IL-4 induces activated B cells to enter the S and G2/M phases of the cell cycle and the addition of IL-4 to preactivated B cell cultures permits the recovery of three- to fourfold more B cells after 4 days of culture. IL-4 and the low m.w. BCGF act in concert to induce the proliferation of anti-IgM-preactivated B cells as demonstrated by [3H]dThd uptake and cell cycle analysis. In striking contrast to the demonstrated antagonistic effect of interferon-gamma on the IL-4-induced expression of the low affinity receptor for IgE (Fc epsilon RL/CD23), on B cells, it was found that interferon-gamma enhanced the IL-4-induced proliferation of anti-IgM-preactivated B cells. Finally, it was found that IL-4 had to be present continuously during the culture period to exert an optimal growth-promoting effect on B cell blasts. As a conclusion, IL-4 is able to induce the proliferation of an appropriately activated subpopulation of human B cells. PMID- 3112226 TI - Regulation of murine T cell proliferation by B cell stimulatory factor-1. AB - The proliferation of mitogen-activated primary T cells, antigen-activated memory T cells from mixed leukocyte culture, and antigen-dependent alloreactive T cell clones in response to purified murine recombinant B cell stimulatory factor-1 (also known as interleukin 4) was examined. We found that B cell stimulatory factor-1 (BSF-1) stimulated optimal proliferation of these T cells only after their recent activation by antigen or mitogen. Analysis of cell surface BSF-1 receptor expression indicated that although T cell activation is accompanied by a small increase in BSF-1 receptor expression, the cells also express BSF-1 receptors prior to activation at a time when they do not proliferate in response to BSF-1. BSF-1 was as effective a stimulus as interleukin 2 for inducing proliferation of the Lyt-2+ subpopulation of concanavalin A-activated murine spleen cells and an alloreactive cytolytic T cell clone. However, the L3T4+ subpopulation of concanavalin A-activated spleen and an alloreactive helper T cell clone were less responsive to BSF-1 than to interleukin 2. Taken together, the data indicate an important role for BSF-1 in the regulation of normal T cell proliferation. PMID- 3112227 TI - Membrane-associated interleukin 1 is required for the activation of T cells in the anti-CD3 antibody-induced T cell response. AB - To establish the role of the membrane-associated form of IL 1 in T cell activation, we tested the accessory function of monocytes (Mo) that were unable to secrete or release soluble IL 1. The data obtained show that strictly purified resting T cells start to proliferate in response to anti-CD3 antibody (OKT3) stimulation in the presence of paraformaldehyde (PFA)-fixed Mo or 3-day cultured Mo (macrophages). The findings that i) PFA-fixed Mo did not produce or release IL 1, ii) the accessory function of PFA-fixed Mo could be inhibited with pretreatment with anti-IL 1 antibody, iii) PFA-fixed Mo had a comitogenic effect in the murine thymocyte assay, and iv) there was a temporal difference between the capacities to function in the comitogenic assay and to produce soluble IL 1, suggest that human Mo can express membrane-associated IL 1 and that it is functionally relevant. PMID- 3112228 TI - Plasminogen activator-specific inhibitors in mouse macrophages: in vivo and in vitro modulation of their synthesis and secretion. AB - Mouse resident peritoneal macrophages synthesize two plasminogen activator specific inhibitors (PAI) that are functionally and antigenically related, but differ in their apparent Mr and oligosaccharide content. Most of the Mr 40,000 inhibitor can be recovered from the cell lysate, whereas the Mr 55,000 glycosylated PAI is preferentially secreted. The murine macrophage PAI are functionally similar and immunologically related to PAI synthesized and secreted by human monocytes-macrophages, and to a PAI from human placenta (PAI-2). PAI production by murine mononuclear phagocytes can be modulated both in vivo and in vitro. Bone marrow-derived macrophages do not produce detectable PAI, whereas inflammatory macrophages obtained from thioglycollate-induced peritoneal exudates produce only low levels of PAI. In cultures of resident peritoneal macrophages, phorbol myristate acetate and cholera toxin increase the synthesis of the Mr 55,000 secreted PAI, whereas dexamethasone decreases the synthesis of both PAI; the production of PAI is also enhanced in the presence of macrophage colony stimulating factor (CSF-1). The overall proteolytic activity of mononuclear phagocytes thus depends in part on the controlled synthesis and secretion of PAI. The balance between the production of plasminogen activators and of their inhibitors could be critical in determining the level of plasminogen-dependent extracellular proteolysis associated with different phases of the inflammatory response. PMID- 3112229 TI - Differential antimicrobial activity of human mononuclear phagocytes against the human biovars of Chlamydia trachomatis. AB - The antimicrobial activities of human mononuclear phagocytes against Chlamydia trachomatis were investigated. Phagocytes cultured for 7 days or less were efficiently microbicidal. Almost complete inactivation of organisms from both human biovars was observed after 48 hr of incubation. However, organisms from the lymphogranuloma venereum (LGV) biovar survived in mononuclear phagocytes infected after 8 days or more in culture, whereas those from the trachoma biovar continued to be killed by such cells. Phagocytes cultured as long as 21 days killed the trachoma organisms with the same effectiveness as those cultured for 7 days or less. An ultrastructural study of inoculated phagocytes illustrated phagolysosomal fusion with degradation of organisms from either biovar in phagocytes which had been cultured for 24 hr before infection. Phagolysosomal fusion was not observed in cells which had been cultured for 8 days or more and then infected with LGV. The addition of interferon-gamma to these macrophages partially restored the phagocytes' microbicidal activity for LGV. Furthermore, a synergistic effect was observed when eosinophil peroxidase was added with interferon. Specific antibody failed to neutralize the infectivity of LGV organisms in 8-day or older mononuclear phagocytes. The findings may reflect the differences in disease syndromes between the two biovars, with the trachoma biovar causing more peripheral diseases and the LGV biovar causing a more systemic disease, with lymph node involvement as its main syndrome. PMID- 3112230 TI - Cellular and humoral immunity to Leishmania major in genetically susceptible mice after in vivo depletion of L3T4+ T cells. AB - Depletion of critical T cell subsets in vivo by treatment with anti-L3T4 antibody (mAb GK1.5) enables BALB/c mice to heal subsequent Leishmania major infection. To investigate the mechanisms by which healing is established, anti-leishmania cellular and humoral responses in anti-L3T4-treated BALB/c mice were compared to those in control BALB/c and genetically resistant C57BL/6 mice. Lymph node and spleen cells were harvested from L. major-infected animals at 1, 2, 3, 4, and 8 wk post-infection and examined in vitro for concanavalin A- or L. major antigen (either promastigote or amastigote)-induced IFN-gamma production. Serum was harvested for Western blot analysis against L. major promastigote antigens. Lymph node cells from resistant C57BL/6 mice generated Leishmania antigen-induced IFN gamma that was maximal by 3 wk; spleen cell IFN-gamma production peaked a week later. Lymph node and spleen cells from susceptible BALB/c mice generated minimal levels of IFN-gamma activity in response to Leishmania antigen stimulation throughout the experiment. Lymph node and spleen cells from BALB/c mice which had been pretreated with GK1.5 generated IFN-gamma in response to Leishmania antigens in vitro at levels that approached those generated by C57BL/6 mice. When splenic mRNA from infected animals was hybridized with a labeled murine IFN-gamma cDNA probe, there were corresponding differences in the amount of IFN-gamma message present, demonstrating that the differences observed in IFN-gamma production in vitro were also apparent in vivo, and were due to differences in transcription. In contrast to C57BL/6 mice which generated only a limited array of Leishmania specific antibodies, BALB/c mice produced antibodies which reacted with a large number of Leishmania antigens. The GK1.5-treated BALB/c mice developed Leishmania specific antibodies at a slower rate than did untreated BALB/c mice. However, by 8 wk after infection, the humoral responses of the anti-L3T4-treated BALB/c mice and the untreated BALB/c mice were comparable. These data document the kinetics of ascending immunity from the draining local lymph nodes to the spleen and confirm, both in vitro and in vivo, the correlation of IFN-gamma production with control of infection in leishmaniasis. Further, an L3T4+ T cell subpopulation may be incriminated in the failure of genetically susceptible BALB/c mice to activate curative cell-mediated immunity in response to Leishmania antigens. PMID- 3112232 TI - Maleylated bovine serum albumin triggers cytolytic function in selected populations of primed murine macrophages. AB - The complex algal polysaccharide fucoidan has been reported as serving as a second signal for activation of macrophages primed in vivo by BCG. To assess the potential utility of this observation in analyzing biochemical mechanisms involved in macrophage activation, we examined the triggering effects of maleylated bovine serum albumin (maleylated-BSA), a defined molecule that clears via similar mechanisms. Cytolysis of P815 mastocytoma targets was triggered by maleylated-BSA, in a dose-dependent manner, in murine peritoneal macrophages primed in vivo by BCG. Unlike bacterial LPS, which triggered cytolysis when used to pretreat the macrophages, maleylated-BSA was only effective if present throughout the period of macrophage-target cytolytic interaction. Maleylated-BSA alone did not lyse the P815 targets and did not affect the binding of such targets by macrophages. Maleylated-BSA was equally effective in triggering cytolysis in BCG-primed macrophages from C3H/HeJ or C3H/HeN mice. Macrophages primed in vitro with IFN-gamma, however, could not be triggered by maleylated BSA, even though these macrophages bound maleylated-BSA comparably to the BCG primed macrophages. When responsive macrophages were fully activated in vitro by IFN-gamma and LPS and then allowed to decay to the primed state, maleylated-BSA was then as effective as LPS in triggering cytolysis. Taken together, the results indicate that maleylated-BSA can trigger cytolysis in certain populations of primed macrophages but not in others. PMID- 3112233 TI - Bi-specific monoclonal antibodies: selective binding and complement fixation to cells that express two different surface antigens. AB - A new dimension of immunotherapeutic selectivity might be achieved if antibodies could distinguish cells that co-express two different surface antigens. Bi specific monoclonal antibodies (BSMAB) with two different antigen combining sites that share a common Fc region theoretically might have such a potential. Two such BSMAB were produced by hybrid-hybridoma clones prepared by fusion of pre-existing hybridomas and were purified by isoelectric focusing. CD3,4 (IgG2a, IgG2b) recognizes the T cell surface antigens CD3 and CD4, and CD3,8 (IgG2a, IgG2a) recognizes CD3 and CD8. These BSMAB promote complement-mediated lysis of target cells that bear both surface antigens 25 to 3125 times more efficiently than those that express only one of the antigens. This selectivity results from the increased avidity of these antibodies for cells with both antigens, as reflected by the increased surface immunoglobulin concentration detected by flow cytometry. It was also demonstrated that there exists a threshold surface immunoglobulin density necessary for antibody-dependent complement-mediated cytotoxicity microtiter assays for the various IgG antibodies tested in both bivalent and monovalent binding. These results support the associative model of IgG-mediated complement fixation. PMID- 3112231 TI - Constitutive and induced expression of the individual HLA-DR beta and alpha chain loci in different cell types. AB - The HLA-DR subregion of the human major histocompatibility complex encodes molecules involved in the regulation of the immune response. These HLA class II molecules are transmembrane heterodimers composed of an alpha and a beta chain. The polymorphic beta chains are encoded by multiple, highly homologous loci, whereas the alpha chain is encoded by a single, nonpolymorphic locus. HLA-DR is expressed constitutively on B lymphocytes and on activated T lymphocytes. It can also be induced by interferon-gamma on most nonlymphoid cells. In a quantitative study of the expression of the individual DR beta chain loci, we have investigated: the levels of mRNA transcripts of the two functional DR beta loci (beta I and beta III) in B cells of various haplotypes; whether both beta chain loci are expressed in activated T cells and, if so, the level of expression of each; whether both loci are expressed in interferon-gamma-induced nonlymphoid cells. This analysis relied on locus-specific DR beta chain oligonucleotide probes. Expression of both the beta I and the beta III loci was observed in all cell types and in all haplotypes tested. In every case the amount of beta I mRNA was about 5 times higher than that of beta III mRNA. This indicates a controlled and coordinated regulation of the mRNA levels of these two HLA-DR loci under all conditions of major histocompatibility complex class II gene expression. PMID- 3112234 TI - T cell growth without serum. AB - Most in vitro T cell proliferation experiments are performed by using serum supplemented medium, yet the actual contributions of serum components to cell cycle progression remain ill-defined, thus complicating attempts to fully define requirements for cell division. By utilizing a functional separation between T cell receptor-triggered "competence" and IL 2-promoted "progression" to independently assess serum requirements during each cell cycle stage, it was shown that serum serves an essential, active role only during the early events of the competence phase (G0-G1 transition) of T cell activation. Serum is required for optimal IL 2 production and the cell surface expression of IL 2 receptors after the stimulation of the T3/Ti antigen receptor complex. In contrast, serum does not function actively during IL 2-mediated progression through the G1 phase of the cycle. Serum proteins serve only a passive role at this stage, preventing the adsorption of IL 2. This same effect can be provided by any number of proteins including IL 2 itself, or even a high cell concentration. Supplementation of serum-free T cell cultures solely with IL 2 and transferrin is sufficient for maximal T cell proliferation, although the time of the peak response is delayed owing to a suboptimal rate of IL 2 receptor expression. Accordingly, the realization that serum is only necessary for the earliest stage of T cell activation will now enable studies designed to identify the critical individual serum components and to define their mechanism of action. PMID- 3112235 TI - The use of fluorescence quenching in flow cytofluorometry to measure the attachment and ingestion phases in phagocytosis in peripheral blood without prior cell separation. AB - Flow cytofluorimetry identifies and quantifies cell markers of different leukocyte subpopulations by combining cytofluorimetry with the differences in the light scattering properties of the leukocytes in mixed populations. In the phagocytic assay, reported in this paper, the experimental conditions were selected in such a way that it was possible to analyse the phagocytic function of granulocytes in peripheral blood without time-consuming cell separation. The percentage of phagocytosing granulocytes was not dependent on the concentration of granulocytes at the selected incubation time and particle (yeast-C3b) concentration. Furthermore, it was possible to adapt a previously described fluorescence quenching technique (FQ method) to differentiate between attachment and ingestion. Crystal violet, originally used in the FQ method, could not be used in this assay due to its lysomotropic effect. Trypan blue at a concentration of 0.25 mg/ml or higher at pH 4.5 showed a plateau effect in fluorescence quenching indicating an effect on attached but not ingested particles. This assay offers a simple technique to screen the functional properties of phagocytic cells in peripheral blood. PMID- 3112236 TI - Application of flow cytometry to immunohematology. AB - A method is described for applying flow cytometry to the analysis of populations of red blood cells that have been sensitized, in vivo or in vitro, with IgG antibody. Specific instrument settings and details of the method are given with sufficient explanation for practical use in immunohematologic investigations. PMID- 3112237 TI - Distinct culture requirements for activation and proliferation of human peripheral blood B lymphocytes by Staphylococcus aureus Cowan strain and growth factors. AB - The concentration of fetal calf serum (FCS) and the culture period were the crucial culture conditions in measuring B cell growth factor (BCGF) and IL-2 activity in vitro. Higher concentrations of FCS (10-15%) significantly inhibited BCGF activity; whereas, lower concentrations of FCS (less than 2.5%) were not sufficient for the response to IL-2. Kinetic experiments showed that the culture period for BCGF should be shorter than that for IL-2, while BCGF in combination with IL-2 induced a synergistic proliferation of B cells in a longer culture period. Adding BCGF after 48 h of SAC stimulation reduced the reaction. Hence, the conventional method using preactivated B cells does not measure BCGF but mostly IL-2. Furthermore, minute amounts of BCGF activity can be more sensitively determined by co-culturing with fixed amounts of IL-2. PMID- 3112238 TI - A rapid fluorescent assay to distinguish attached from phagocytized yeast particles. AB - In studies of phagocytosis and its consequences for cell activation, it is important to distinguish those particulate stimuli which are completely ingested and internalized from those which are only attached to phagocytic surfaces. Ingestion can be profoundly influenced by both the type of opsonins on the surface of the stimulus and the expression and activation of receptors on the phagocytes for these opsonins. We report a new fluorescent assay which facilitates rapid and reproducible quantitation of attached versus fully internalized live or dead yeast particles by phagocytes. The assay employs the fluorescent dye diaethanol (Uvitex 2B) which stains chitin on the cell wall of fungi and is excluded from live phagocytes. The diaethanol assay and a standard, previously published methylene blue dye exclusion assay yielded comparable results using human neutrophils or monocytes incubated with heat-killed, serum opsonized Candida albicans. The diaethanol assay proved useful in distinguishing differences in effects of various opsonins, as human neutrophils selectively opsonized with either pooled human serum (PHS), IgG (heat-inactivated PHS) or complement (IgG-depleted PHS) completely internalized 69.5%, 91.3% and 52.5% of cell-associated zymosan particles respectively. Finally, the new assay permitted comparisons of differing macrophage populations, as resident murine peritoneal macrophages internalized only 10.6% of complement-opsonized, cell-associated zymosan particles compared with 41.7% when the macrophages were elicited with thioglycolate. The assay should prove useful to investigators studying both fungal phagocytosis and killing, as well as to those performing general studies of receptor expression, regulation and function. PMID- 3112239 TI - Rapid, quantitative microassay for the monokine respiration inhibitory factor. AB - The murine monokine respiration inhibitory factor (RIF) induces lesions at Complex I and Complex II of the mitochondrial electron transport chain (ETC) of tumor cells; these lesions in the ETC appear closely linked with cytostasis of the targets. In this report we describe the use of the sensitive murine mammary adenocarcinoma line EMT-6 in a colorimetric microassay for the effects of RIF on the ETC and target replication. The participation of cytolytic molecules in this assay system was excluded because of the resistance of the target to their effects. The endpoint for the assay was the ETC-mediated reduction of 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to its colored formazan. The two major coupling sites of MTT in the ETC of EMT-6 cells are shown to be proximal to Coenzyme Q, detected either by malate oxidation through Complex I or succinate oxidation through Complex II. The assay was sensitive to both RIF induced lesions at these dehydrogenases and to the cytostasis-linked reduction in target cell number. The assessment of ETC lesions by this microassay correlated directly with that determined by the less sensitive polarimetric assay based on oxygen consumption. We demonstrate the application of this microassay to parameters for the production of RIF by activated murine macrophages, and to initial molecular characterization of this mediator. PMID- 3112240 TI - Direct and indirect immunofluorescence analysis of bacterial populations by flow cytometry. AB - Bacillus anthracis spores and Escherichia coli were stained with fluorescein conjugated antibody using direct and indirect methods, then analyzed by means of a commercial flow cytometer. To reduce the cytometer's fluorescence component resulting from unreacted conjugate, reaction mixtures were either diluted or were centrifuged through a sucrose solution using a moving zone technique. Evidence is produced that the fluorescence statistics for centrifuged samples closely represent the fluorescence distribution of stained single bacteria in the reaction mixture at the end of incubation; in particular, centrifugation did not cause aggregation of bacteria. Centrifugation is proposed as more effective than mere dilution for use with a wide range of bacterial concentrations, and the moving zone technique is to be preferred to conventional centrifugation in which bacteria tend to aggregate in the pellet. In indirect assays, it was shown that the washing step after reaction with antibacterial antibody may be omitted. The performance of direct and indirect staining methods was compared, including the use of either Staphylococcus aureus protein A or polyclonal sheep anti-rabbit antibody as the indirect reagent. When the bacterial concentration in reaction mixtures was increased the median fluorescence intensity fell, indicating that specific antibody had become limiting at low concentrations of the polyclonal antibody preparations. The implications of this for the design of flow cytometry assays of bacteria are discussed. PMID- 3112241 TI - An epidemic of penicillin-tolerant group A streptococcal pharyngitis in children living in a closed community: mass treatment with erythromycin. PMID- 3112242 TI - Strain-dependent difference in susceptibility of mice to experimental ascending pyelonephritis. PMID- 3112243 TI - Influence of monoclonal antibodies against HLA class I and class II antigen on interferon-gamma and -alpha induction. AB - The effects of several monoclonal antibodies (MAbs) directed against different epitopes of HLA class I and class II antigens on interferon (IFN)-gamma and IFN alpha production were studied. The results indicate that: these MAbs have a marked inhibitory effect on the production of IFN-gamma induced by alloantigens and microbial antigens; they influence only to a lesser extent staphylococcal enterotoxin B (SEB)- and phytohemagglutinin (PHA)-induced IFN-gamma production; such effects parallel inhibition of lymphoproliferation except for PHA-induced blastogenesis, which is not affected; on the other hand, these MAbs have no effect on the production of IFN-alpha induced by lipopolysaccharide (LPS) or viruses. PMID- 3112244 TI - Differential purification by immunoaffinity chromatography of two carboxy terminal portion-deleted derivatives of recombinant human interferon-gamma from Escherichia coli. AB - Two lower-molecular-weight derivatives of recombinant human interferon-gamma (rIFN-gamma) were purified concurrently from a lysozyme-EDTA extract of Escherichia coli cells by immunoaffinity chromatography using a monoclonal antibody (MAb) against a synthetic carboxy-terminal peptide (Lys-131-Gln-146). The two derivatives, 15K rIFN-gamma and 17K rIFN-gamma, were regarded to have been generated at the extraction step. They were successfully separated from each other by using another MAb against the same synthetic peptide with higher binding affinity than the first. The results of protein-chemical analyses indicate that 15K rIFN-gamma and 17K rIFN-gamma lack 15 (Arg 132-Gln-146) and 4 (Arg-143-Gln 146) carboxy-terminal amino acid residues, respectively. All the data suggest that the two derivatives form a noncovalent dimer and that 15K rIFN-gamma binds indirectly to the MAb column via 17K rIFN-gamma. PMID- 3112245 TI - Recombinant interferon-gamma stimulates the production of human tumor necrosis factor in vitro. AB - Human peripheral blood monocytes in culture secrete tumor necrosis factor (TNF), which can be detected with a sensitive enzyme-linked immunosorbent assay system. When recombinant human interferon-gamma (rIFN-gamma) is added to cultured cells, TNF production is increased. rIFN-gamma is also able to sustain the elevated production level of TNF over a 4-day period. Recombinant interferon-alpha (rIFN alpha) was unable to stimulate increased TNF production. Unstimulated mononuclear phagocytes and rIFN-alpha-treated cells decreased secretion of TNF over a 4-day interval. The stimulatory effect of rIFN-gamma was dose dependent and required both new RNA and protein synthesis and was independent of endotoxin in the tissue culture medium. PMID- 3112246 TI - Activation of mouse macrophages for migration inhibition and for tumor cytotoxicity is mediated by interferon-gamma priming and triggering by various agents. AB - The requirements for activation of C3HeB/FeJ mouse peritoneal macrophages to mediate migration inhibition from capillary tubes was compared with those conditions prerequisite for nonspecific tumor cytotoxicity. Both in vitro assays for macrophage activation were found to require a two-stage process that involved priming by murine recombinant interferon-gamma (IFN-gamma) and triggering by subactivating concentrations of bacterial lipopolysaccharide (LPS), Lipid A, Polyinosinic-polycytidylic acid (poly I:C), or cobra venom factor (CVF). A dose related increase in both migration inhibition and tumor cytotoxicity was shown with increasing concentrations of IFN-gamma (3.0-50.0 U/ml) in synergistic combination with an LPS trigger. IFN-gamma alone produced low levels of migration inhibition or tumor cytotoxicity, only at higher concentrations, that was not attributable to LPS contamination. The concentrations of the various agents required for direct activation or triggering of IFN-gamma-primed macrophages were approximately 2- to 10-fold greater for migration inhibition than for tumor cytotoxicity. Our results indicate that the two-signal process of priming and triggering for mediating mouse macrophage nonspecific tumoricidal activity is also operative in migration inhibition from capillary tubes. Thus, under defined conditions with purified lymphokines, the migration inhibition assay appears to be a reliable alternate in vitro correlate of macrophage activation by IFN-gamma. PMID- 3112247 TI - In vivo hyperthermia enhances plasma antiviral activity and stimulates peripheral lymphocytes for increased synthesis of interferon-gamma. AB - The effect of in vivo hyperthermia on plasma interferon (IFN) activity and on the induction of IFN-gamma by phytohemagglutinin (PHA) or staphylococcal enterotoxin B (SEB) in isolated leukocyte cultures was investigated. Adult rhesus monkeys (Macaca mulatta) were placed in a climatic chamber maintained at 45 degrees C until their core body temperatures increased 2 degrees C above control levels. Peripheral blood samples were withdrawn both prior to core temperature elevation and at the time of peak body temperature. Plasma IFN-alpha increased slightly from a control value of 12 U/ml to 16 U/ml at the elevated core temperature. However, this alteration of plasma IFN levels appears to be a complex process that includes the loss of certain circulating IFN-alpha subtypes and the influx of acid-labile (Type II) IFN-alpha. Additionally, a non-IFN antiviral factor present in the plasma was elevated 10-fold at the higher body temperature. When mononuclear cells were isolated and cultured at 37 degrees C in the presence of PHA or SEB, those cells isolated from animals at the peak of body temperature showed a 4- to 16-fold increase in IFN-gamma activity relative to cells isolated from the same animal before the temperature increase. Similar results were obtained with cells isolated when fever was induced by the systemic injection of nonviable Escherichia coli. These results demonstrate that increased body temperature results in a circulating lymphocyte pool which is "primed" for the production of elevated levels of IFN-gamma activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112249 TI - Effect of treatment with interferon-gamma and concanavalin A on the course of infection of mice with Salmonella typhimurium strain LT-2. AB - Lymphokines have been shown to affect the resistance of mice to bacterial infections. To explore this effect further, mice were pretreated with 34 units per day for 5 days of a hybridoma supernatant containing primarily interferon gamma activity. Then, the mice were infected with one LD50 of Salmonella typhimurium strain LT-2. The hybridoma supernatant fluid-treated mice were not protected; in fact, they died faster than did mice only infected with S. typhimurium. When mice were pretreated under the same regimen with pure murine IFN-gamma produced by recombinant DNA technology prior to infection, the mice were protected and 95% survived the infection. The hybridomas had been treated with concanavalin A (ConA) to induce IFN-gamma. When mice were directly treated with ConA prior to infection with S. typhimurium, they also died more quickly than untreated controls. These data suggest that IFN-gamma pretreatment can protect mice against infection with S. typhimurium, but that ConA pretreatment can counteract that effect. PMID- 3112248 TI - Characterization of an interferon-resistant mutant of the human breast cancer cell line BT-20. AB - The human breast cancer cells BT-20 were treated for 18 months in the continuous presence of interferon-gamma (HuIFN-gamma; 500 U/ml). These cells have become completely resistant to HuIFN-gamma and interestingly also to IFN-alpha 2. However, the expression of HLA-DR and the regulation of cell adhesion to tissue culture plastic remained partially under the domain of HuIFN-gamma. A reduced number of IFN-gamma binding sites in comparison to the wild-type cells were observed on the IFN-resistant BT-20 cells. PMID- 3112250 TI - Angiotensin II regulates interferon-gamma production. AB - An extensive literature links the immune responses to neuroendocrine regulation. We have examined the effects of the neuropeptide hormone angiotensin II on the production of the immunomodulatory lymphokine interferon-gamma (IFN-gamma). Angiotensin II (10(-6)-10(-8) M) stimulated (three- to fivefold) the IFN-gamma production in human blood lymphocytes obtained from normal individuals. At 10(-9) M angiotensin II stimulation disappeared and was reestablished at physiological concentrations of the neuropeptide (10(-10)-10(-11) M). Stimulation by angiotensin II was compared with the classical effect of the lectin phytohemagglutinin, and it was seen that both actions are mediated by external calcium (as they are blocked by EGTA 2.5 mM) and that the stimuli follow different kinetics, reaching the steady state at 6 h with angiotensin II and later (18 h) when the lectin was used. The effect of angiotensin II over the IFN gamma production was blocked by its analog sarcosine 1-isoleucine 8-angiotensin II, showing the specificity of angiotensin II action. These findings demonstrate a selective biological regulation of IFN-gamma production by angiotensin II and suggest another regulation pathway of immune responses. PMID- 3112251 TI - Oligomeric structure of recombinant human and murine immune interferons by means of sedimentation equilibrium. AB - The oligomeric structure of two recombinant human immune interferon species, one with Cys-Tyr-Cys-Gln [( Cys-Tyr-Cys]rHu-IFN-gamma) and the other with Met-Gln-Asp Pro (rHu-IFN-gamma) as the amino-terminal residues, and a recombinant murine immune interferon [( Cys-Tyr-Cys]rMu-IFN-gamma) were examined by means of sedimentation equilibrium. All three IFN-gamma s existed as dimers under nondenaturing conditions. Both [Cys-Tyr-Cys]rHu-IFN-gamma and [Cys-Tyr-Cys]rMu IFN-gamma formed higher oligomers, tetramers, and octamers, respectively, under oxidative conditions, whereas rHu-IFN-gamma remained as dimers. PMID- 3112252 TI - An unusual membrane specialization of mammalian cells in vitro. AB - An unusual membrane specialization, termed "particle rows," was revealed by freeze-fracture electron microscopy in cultured mammalian cells including dissociated central nervous system tissue and peripheral connective tissue. The specialization consisted of rows of particles slightly elevated on the P fracture face, with a regular periodicity of 35 nm between the rows and a uniform length of the rows of 100 nm. It was usually associated with caveolae (pits) and sometimes accompanied gap junctions, or tight and gap junctional complexes within the same membrane. The particle rows are probably expressed by more than one cell type, all in immature form. PMID- 3112253 TI - Condylar position following ramus osteotomy and functional osteosynthesis. A clinical function-analytic and computer tomographic study. AB - Opponents of the application of a stable fixation of the fragments with compression screws in osteotomies of the mandibular ramus quite often claim that there is the possibility of a postoperative dislocation of the proximal fragment with consequent functional disturbances of the temporo-mandibular joint. For determination of the frequency and the extent of such possible displacements of the condyle, a total of 174 patients, in whom ramus osteotomies were performed, were clinically examined. In 9 of them, a functional analysis and in 10 other patients, a CT scan investigation of the position of the TM joint, was carried out. Only in 1 case could a considerable dislocation of the proximal fragment be observed, which was due to a strong unilateral deviation of the ascending ramus. For correction of the functional disturbance the bone screws had to be removed in this particular case. In those cases where a functional analysis and CT study were undertaken, only slight changes of the pre- and post-operative position of the condyles were observed: it did not lead to clinical disturbances and complaints. PMID- 3112254 TI - Maxillofacial injuries at Jordan University Hospital. AB - In the Jordanian Society many factors contributed to the occurrence of maxillofacial injuries. Analysis of 131 cases of maxillofacial injuries indicated higher involvement of males. The most susceptible age group was 0-5 years; mandibular fractures were commoner than those of the middle third of the face. In Jordan the incidence of violence is less frequent than that of road traffic accidents. Shattered automobile glass is by far the most common cause of facial injuries. The use of seat-belts notably reduced the frequency of severe facial injuries. The findings of this study should alert the authorities to the need for the establishment of a maxillofacial unit in every city, as major problems concerning the identification and management of such cases still exist in developing countries like Jordan. PMID- 3112255 TI - Sialodochoplasty--does it work? AB - Isotope scanning of the salivary glands was carried out post-operatively on 8 patients who had sialodochoplasty carried out by the Wilkie technique. This showed reduced function to a varying degree in every parotid gland whose duct was repositioned, indicating some atrophy, but there was still sufficient function to justify the procedure. PMID- 3112256 TI - Preprosthetic mandibular vestibuloplasty with split-skin graft. A 2-year follow up study. AB - 17 patients with lower denture malfunction problems related to insufficient residual ridges had a vestibuloplasty with split-skin graft performed in the mandible under local analgesia on an out-patient basis. The patients were followed-up for 2 years and records of vestibular extension showed a maximum of relapse at the 1-month control (24%). Most of the lost extension was regained at the 6-month check, and the 2-year outcome was 92% of the surgically-created vestibular sulcus extension as a mean value of records obtained at the midline and canine regions. A comparison with a previous study on buccal mucosal graft vestibuloplasty led to the conclusion that free grafts of skin and buccal mucosa prevent a relapse equally well under the same circumstances. 13 patients were satisfied with the improvement achieved, 3 reported fair, and 1 was dissatisfied with the result of the operation. The split-skin graft underwent a change of appearance in 5 cases interpreted as a skin graft candidosis. Indication of this condition accelerating the residual ridge resorption is discussed. PMID- 3112258 TI - Allotransplantation of human teeth. A retrospective study of 73 transplantations over a period of 28 years. AB - An assessment was made of the postoperative fate of 73 allotransplanted human teeth carried out by 3 surgeons between 1956 and 1980 to determine the clinical and radiographical course of immunogenetically unmatched allotransplanted human teeth. The mean ages of recipients and donors were 34.1 and 15.2 years, respectively; 47 of the grafts had incomplete root-formation at time of transplantation. Mean observation period was 7.8 years with a maximum of 28 years. The study was terminated December 1985. The mean functional time of the grafts (function of graft without symptoms) was 6.8 years (max. 28.5 years). No signs of pulpal survival were found in any graft. Root resorption was found in 91.6% of grafts within a mean of 8.8 months after transplantation, causing a high frequency of graft loss within the first 2 years (34.1%). Recipients older than 45 years of age retained the grafts significantly longer than young patients. The major causes of graft loss were replacement (60.3%) and inflammatory resorption (24.4%). Graft loss due to marginal periodontitis was minor (2.7%). Inflammatory resorption, which was found more frequent in young recipients (P = 0.02), usually caused rapid rejection, whereas the survival time after ankylosis was significantly longer. In conclusion, no clinical or radiographical evidence of long-term survival of the pulpal or periodontal tissues of the unmatched allografts were found. However, despite a progressing replacement resorption frequently present, the allografts seem to function clinically sufficient, symptomless and often with clinically normal gingival condition for many years. Increasing age of the recipient at time of transplantation significantly increased the function time of the graft. Younger recipients showed more inflammatory resorption of the grafts. PMID- 3112257 TI - Local anaesthesia and dry socket. A clinical investigation of single extractions in male patients. AB - 1533 single intra-alveolar permanent tooth extractions in males were investigated in a study to determine if the type and technique of local anaesthesia influenced the occurrence of dry socket. The results show that the incidence of dry socket was significantly greater after the use of Xylocaine compared to Citanest and that the use of repeated injections or intraligamental techniques increased the likelihood of this painful post-extraction condition. PMID- 3112259 TI - Normal and abnormal temporomandibular joints: quantitative evaluation of inferior joint space arthrography. AB - Arthrography has been shown to provide important diagnostic information in patients with temporomandibular joint (TMJ) dysfunction. In this study, 60 arthrograms on totally asymptomatic patients and 64 arthrograms on symptomatic patients were evaluated. Quantitative evaluation of inferior joint space arthrography was performed with the help of a computer digitizing morphometry program. Results indicate a significant difference in the areas of the anterior and posterior recesses between normal and abnormal joints in the closed-mouth position. Differences between the 2 groups also exist in linear measurements of the anterior recess. This data further defines important diagnostic criteria in the arthrographic evaluation of both the normal and abnormal TMJ. PMID- 3112260 TI - Outcome of treatment of patients with orofacial discomfort complaints. AB - In 113 patients with a wide variation of orofacial and general complaints, which they assumed were caused by galvanic currents and/or metallic restorations, the initial and long-term development (3 years) after treatment was studied. Many treatment procedures were tried; besides information and follow-ups, each patient underwent in average of 6.6 different measures. The often time-consuming treatment was individualized, based on each patient's signs and symptoms. Besides conventional dental treatment, stomatognathic therapy and medical treatment which were frequently needed, metallic constructions were removed in 54% of the patients. The initial outcome of treatment was evaluated as successful both by patients and therapists in about 80%, but half of the patients reported recurrences, more often after removal of metallic constructions than after other dental treatment, while the dentists found recurring clinical signs in only 13% of the patients and without correlation to type of treatment. It is concluded that these patients need a careful oral examination and dental treatment of observed local pathology and defects of dental constructions, but removal of metallic constructions should be avoided when not indicated. Many of these patients will also need medical consultation and treatment, and a collaboration between the dentist and the physician is then recommended. PMID- 3112261 TI - Postoperative pain control for outpatient oral surgery. AB - 16 healthy patients requiring removal of bilateral symmetrically-impacted mandibular third molars participated in a double-blind randomised crossover trial to test the effectiveness of postoperative pain control using a long-acting anti inflammatory agent (diflunisal) in combination with a long-acting local anaesthetic agent (bupivacaine). Results were compared to the more traditional method of using an oral analgesic with shorter duration of action (paracetamol with codeine) with lignocaine as the local anaesthetic. Using a visual analogue pain scale, patients reported that significantly reduced pain was experienced over the first 4 days postoperatively with the diflunisal/bupivacaine treatment and patient preference for this treatment was highly significant. This report represents the first such study of diflunisal used for an extended course in oral surgery with pain assessment over the same period. No significant side-effects or adverse reactions were encountered. PMID- 3112262 TI - Intravenous midazolam in oral surgery. AB - Intravenously administered midazolam (0.1 mg/kg) was compared with placebo in a randomized study in 50 patients undergoing oral surgical procedures under local anaesthesia. The results obtained from this study showed that midazolam when compared to placebo had slight cardiovascular and respiratory depressant effects, diminished anxiety and caused amnesia. It also provided better operating conditions and possibly stimulated appetite. PMID- 3112263 TI - Oral midazolam sedation in third molar surgery. AB - A double-blind randomised study was designed to assess the value of oral midazolam in patients undergoing minor oral surgery. 30 young healthy Hong Kong Chinese with bilateral symmetrical impaction of lower third molars to be surgically removed in 2 visits, were included in the study. Randomly selected, a powdered midazolam tablet or placebo was given on the 1st visit and the alternative on the 2nd visit. 45 min were given for the drug to act. Surgical removal of the teeth was carried out by a single operator, randomly, one side being done at one visit. The majority who had midazolam were relaxed during the operation. Nearly 75% had partial to complete amnesia. Midazolam sedation lasted about 45 min, produced good operating conditions and stable vital signs with adequate verbal response. The main adverse effects were drowsiness and dizziness on the same day. The majority had never heard of oral sedation being available to supplement local anaesthesia. The majority preferred midazolam to placebo and preferred to have local anaesthesia supplemented with oral sedation for minor oral surgery in the future. PMID- 3112264 TI - Surgicel: macrophage processing of the fibrous component. AB - Previous reports have demonstrated that Surgicel, a local haemostatic agent, is absorbed from implantation sites. In an earlier study, it was shown that the material consists of a uronic acid component and a fibrous residue. A chemically quantified loss of the uronic acid component within 18 h of implantation was demonstrated. The aim of the present study was to examine the fate of the fibrous residue in rat tissues, using both light and electron microscopy. Results indicated that this fibrous component is phagocytosed by macrophages at the site of implantation. A model for the clearance of Surgicel from tissue implantation sites is presented. PMID- 3112265 TI - Clinical considerations from axon-myelin relationship in human inferior alveolar nerve. AB - A histological study analysed the axon-myelin relationships in human inferior alveolar nerve fibres in both transverse and longitudinal sections. Observations on fibres cut in transverse section showed variation in myelin thickness upon axons having approximately the same diameter. Large diameter axons had relatively thinner myelin sheaths than small-diameter axons. A longitudinal reconstruction of a 470 micron length of fibre demonstrated the presence of 13 Schmidt Lantermann clefts. The surgical and clinical implications of these finding are discussed. PMID- 3112266 TI - Orbital apex syndrome. AB - The orbital apex syndrome is a very rare complication of fractures of the facial skeleton, as well as other conditions and is characterized by blindness, fixed dilated pupils, proptosis, ptosis of the eye and ophthalmoplegia. We are reporting such a case we had the opportunity of treating. PMID- 3112267 TI - Uncommon manifestations of histiocytosis X. AB - Histiocytosis X is a group of disorders of uncertain etiology with a variety of manifestations that are usually related to the age of the patient. Treatment consists of local curettage, irradiation and chemotherapy. The prognosis depends on the systems involved. The oral and perioral tissues are occasionally involved and often lead to the diagnosis. We report a case with spinal cord involvement and a case of facial nerve paralysis secondary to involvement of the petrosal bone. Also included is a case of involvement of the mandibular condyle. PMID- 3112268 TI - Paraesthesia of the infraorbital nerve following fracture of the zygomatic complex. AB - 68 patients with fractures of the zygomatic complex were studied. Of these, 56 had sensory disturbances of the infraorbital nerve. 50 patients were operated on and in 42% (21) some degree of persisting hypesthesia was found. No significant difference in outcome was found between the different methods of indirect reduction used. However, in 10 out of 12 patients in which direct fixation with transosseous wiring of the infraorbital margin was performed, persisting hypesthesia was encountered. In 3 out of 4 patients where the nerve was also explored primarily, the sensation returned totally. A secondary nerve deliberation was also found to be beneficial in 4 out of 5 patients with persisting total loss of sensation. PMID- 3112269 TI - Multiple cemento-ossifying fibroma. AB - This report concerns a case of multiple cemento-ossifying fibroma involving the maxilla and mandible of a 55-year-old Japanese male. The clinical, radiographic and histopathological findings are presented and discussed. PMID- 3112270 TI - Osteoma in mandibular condyle. AB - A case of peripheral osteoma occurring in the mandibular ramus in a 26-year-old man is reported. Radiographic examination revealed a pedunculated, protruding globular, bone-like opaque mass around the notch of the right mandibular ramus. Histopathological examination showed a lamellar bone structure with irregular arrangement. Wide trabeculae, narrow interstitial areas, and many fibrovascular channels were detected by scanning electron microscopy. Thus, characteristic findings of a compact osteoma were obtained clinically and histopathologically. PMID- 3112271 TI - Failure of root development of human permanent teeth following irradiation. AB - Complete absence of root formation of the upper incisors, canine and first premolar was reported in a 27-year-old female who had received radiation therapy for a retinal glioma of the right eye at age of 3 years 1 month. Ground and decalcified sections showed no remarkable changes in enamel and dentin of the crowns, but the pulp floor was closed by irregular dentin deposit despite the absence of root formation. The outer surface of the irregular dentin was covered by acellular cementum, and the periodontal membrane was undeveloped. A slight degree of fibrosis was seen in the pulp, but the coronal part of the dentin was lined by odontoblasts. The theory that tooth eruption is caused by the growth of the root is not substantiated by the observation in this case. PMID- 3112272 TI - [Drug-resistance and transferable R plasmids in Vibrio cholerae O-1 and non O-1, V. fluvialis and V. parahaemolyticus recently isolated from human sources]. PMID- 3112273 TI - Co-trimoxazole treatment of two fatal cases of Pneumocystis carinii pneumonia- changes in protozoan morphology and treatment method. PMID- 3112274 TI - [Hyper-IgM-globulinemia associated with pneumonia due to Mycoplasma pneumoniae]. PMID- 3112275 TI - [Infectious disease complicated by hematological disorders--a survey of the past seven years at the First Department of Internal Medicine, Ehime University Hospital]. PMID- 3112276 TI - [A clinical evaluation of mebendazole in trichuriasis in Japan]. PMID- 3112277 TI - [Plasmid profiles and antimicrobial resistance in Salmonella typhimurium, S. enteritidis, and S. braenderup isolates from human sources]. PMID- 3112278 TI - [A child case of infective endocarditis due to methicillin-resistant Staphylococcus aureus--analysis of the therapeutic course and drug sensitivity of detected organisms]. PMID- 3112279 TI - [A case of septicemia due to Enterococcus faecium in an infant]. PMID- 3112281 TI - [Clinical study of the prevention of deep fungal infection by oral administration of large dose of amphotericin-B]. PMID- 3112280 TI - [Acute thrombocytopenic purpura associated with Mycoplasma pneumoniae infection]. PMID- 3112282 TI - [In vitro antibacterial activity of new derivatives of pyridonecarboxylic acid, norfloxacin, ofloxacin, enoxacin and ciprofloxacin, against Vibrio cholerae O-1]. PMID- 3112283 TI - [Clinical study of tsutsugamushi disease in Miyazaki District]. PMID- 3112284 TI - [Clinical studies of the predisposing factors of infectious endocarditis in infants and children]. PMID- 3112285 TI - [Mechanism of respiratory infection due to Streptococcus pneumoniae or Haemophilus influenzae in mice]. PMID- 3112286 TI - [Study of the pathogenicity of Enterococcus faecalis--relationship between infectibility of E. faecalis in mice and its biological activity]. PMID- 3112287 TI - [Bed isolator for prevention of infection in bone marrow transplantation]. PMID- 3112289 TI - [A case of chronic mucocutaneous candidiasis (CMCC) with repeated pulmonary abscess and sepsis]. PMID- 3112288 TI - [Clinical evaluation of carumonam in chronic respiratory infections: double-blind study using cefoperazone as a positive control]. PMID- 3112290 TI - [A case of systemic trichosporon infection associated with acute lymphocytic leukemia]. PMID- 3112291 TI - [A case of meningoencephalitis caused by group F Streptococcus anginosus]. PMID- 3112292 TI - [Hormone therapy of infertility]. PMID- 3112293 TI - [A study on the activity of the PGI2 producing enzyme system derived from maternal and fetal vessels of toxemia of pregnancies]. AB - We investigated the conversion rate from arachidonic acid (A.A.) to PGI2 and the activity of PGI2 producing enzyme system in endothelial cells of umbilical veins (U.V.) and maternal omental veins (O.V.) in normal pregnancy (NOR) and toxemia of pregnancy (TOX). The conversion rate from A.A. to PGI2 for U.V. and O.V. in NOR was higher than that in TOX. There was a significant difference between NOR and TOX with the conversion rate for U.V. at a concentration of 172.4 nM/ml A.A. The apparent Vmax value for PGI2 producing enzyme system (nM/mg) in U.V. in NOR (n = 7) was 0.88 +/- 0.21 (mean +/- S.E.) and that for TOX (n = 3) was 1.63 +/- 0.18. The apparent Km value for the enzyme system (microM) in U.V. in NOR (n = 7) was 0.75 +/- 0.25, and that for TOX (n = 3) was 3.26 +/- 0.78. Significant differences (p less than 0.05) between NOR and TOX were observed with Vmax and Km values. The apparent Vmax value for the enzyme system in O.V. in NOR (n = 3) was 0.32 +/- 0.13, and that for TOX (n = 3) was 2.12 +/- 0.38. The apparent Km value for the enzyme system in O.V. of NOR (n = 3) was 0.26 +/- 0.06, and that for TOX (n = 3) was 0.97 +/- 0.09. There was a significant difference between (p less than 0.05) the Vmax and Km values for NOR and TOX. The present study showed that U.V. (fetal vessel) and O.V. (maternal vessel) in TOX had a lower activity PGI2 producing enzyme system than those in NOR due mainly to an imbalance between the substrate supply and cyclooxygenase activity. PMID- 3112294 TI - [Study on human placental beta-alanine and taurine transport mechanism (using microvillous membrane vesicles]. AB - Using microvillous membrane vesicles prepared from human full term placenta, we studied the placental beta-amino acid transport mechanism. The transport of amino acids into microvillous membrane vesicles was studied by a filtration technique using a millipore filter. The uptake of beta-alanine into microvillous membrane vesicles was dependent on Na+ electrochemical gradient (extravesicular greater than intravesicular). The initial rate of this Na+ gradient dependent beta alanine transport exhibited saturation kinetics with respect to the beta-alanine concentration: an apparent Km of 0.24 mM and Vmax of 46 pmol/mg protein/20 sec were calculated. Taurine inhibited beta-alanine uptake into microvillous membrane vesicles, but on the other hand L-alanine didn't inhibit this beta-alanine uptake. The L-alanine uptake into microvillous membrane vesicles was Na+ electrochemical gradient dependent and the initial rate of this Na+ dependent L alanine uptake into vesicles was faster than the uptake of Na+ itself into vesicles. On the other hand, the initial rate of Na+ dependent beta-alanine and taurine uptake into vesicles was slower than the uptake of Na+ itself into vesicles. These results indicated that there existed a beta-amino acid specific transport system in human placental microvillous membrane, and placental taurine transport was carried out by this system. And it was also indicated that this placental beta-amino acid transport mechanism is quite different from that of L alanine. PMID- 3112295 TI - [Study on the neuroendocrinological control of prolactin release in early puerperium]. AB - The purpose of this study is to investigate the neuroendocrinological control mechanism of prolactin (PRL) acting on the hypothalamo-pituitary axis during early puerperium. The puerperal women consisted of three groups: the breast feeding group (n = 39), the bromocriptine (BRC)-treated group (5 mg/day, n = 17) and naloxone-treated group (1 mg iv, n = 16). In each group, 10 mg metoclopramide (MCP), 500 micrograms TRH or 400 mg cimetidine was given intravenously. 1) The plasma PRL levels increased significantly after the injection of MCP, TRH and cimetidine. The peak values of delta PRL levels were 447.0 +/- 62.3 ng/ml after MCP, 278.3 +/- 65.1 ng/ml after TRH and 86.5 +/- 27.3 ng/ml after cimetidine. 2) This PRL increase after the injection of MCP and cimetidine was suppressed significantly by pretreatment with BRC. However, the PRL increase after TRH was not suppressed by pretreatment with BRC. 3) Naloxone had no significant effect on PRL response to MCP and TRH, since the plasma PRL levels rose significantly after the injection of MCP and TRH in the naloxone-treated group. These results revealed that there were different mechanisms of PRL release in MCP and TRH. Furthermore, the PRL releasing mechanism was influenced by histamine H2-receptor, but was not influenced by opioid peptide in early puerperium. PMID- 3112296 TI - [Monitoring of follicle development with urinary estrogen determination by latex slide test]. PMID- 3112297 TI - [Studies on adenosine deaminase activity and purine nucleoside phosphorylase activity of peripheral blood mononuclear cell in patients with cirrhosis of the liver]. PMID- 3112298 TI - Effects of dietary cholesterol and hypothyroidism on rat apolipoprotein mRNA metabolism. AB - The effects of dietary cholesterol and hypothyroidism on the mRNA levels of rat apolipoproteins A-I, A-IV, and E were measured in extracts of rat liver and rat intestine by hybridization to specific cDNA. Four groups, each comprised of six rats, were fed diets consisting of normal laboratory rat chow and either no supplements (control); 5% lard, 1% cholesterol, and 0.3% taurocholic acid (CF); 5% lard, 1% cholesterol, 0.3% taurocholic acid, and 0.1% propylthiouracil (CF PTU); or 0.1% propylthiouracil (PTU) for 32 days. At the conclusion of the diets, serum cholesterol, triiodothyronine, and thyroxine levels were measured. The average serum cholesterol concentrations for the four groups were 50.4 +/- 3.7, 75.6 +/- 15.3, 135.3 +/- 41.5, and 73.3 +/- 16.4 mg/dl, respectively. The presence of propylthiouracil in the diets significantly lowered triiodothyronine and thyroxine levels in the serum. The mRNA levels for apolipoproteins A-I and A IV in rat liver decreased significantly after the feeding of the CF-PTU diet (31 +/- 4% and 32 +/- 3% of normal, respectively) and the PTU diet (34 +/- 8% and 43 +/- 12% of normal, respectively), but showed little change after the CF diet (88 +/- 16% and 108 +/- 15% of normal, respectively). The effects of dietary propylthiouracil on the hepatic mRNA levels for apolipoproteins A-I and A-IV imply a role for thyroid hormones in regulating the mRNA levels for these apolipoproteins in rat liver. ApoE mRNA levels in the rat liver decreased slightly after the CF-PTU diet (74 +/- 12% of normal) and after the PTU diet (73 +/- 10% of normal).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112299 TI - Pathways in the formation of human plasma high density lipoprotein subpopulations containing apolipoprotein A-I without apolipoprotein A-II. AB - The lecithin:cholesterol acyltransferase (LCAT)-induced transformation of two discrete species of model complexes that differ in number of apolipoprotein A-I (apoA-I) molecules per particle was investigated. One complex species (designated 3A-I(UC)-complexes) contained 3 apoA-I per particle, was discoidal (13.5 X 4.4 nm), and had a molar composition of 22:78:1 (unesterified cholesterol (UC):egg yolk phosphatidylcholine (egg yolk PC):apoA-I). The other complex species (designated 2A-I(UC)complexes) containing 2 apoA-I per particle was also discoidal (8.4 X 4.1 nm) and had a molar composition of 6:40:1. Transformation of 3A-I(UC)complexes by partially purified LCAT yielded a product (24 hr, 37 degrees C) with a cholesteryl ester (CE) core, 3 apoA-I, and a mean diameter of 9.2 nm. The 2A-I(UC)complexes were only partially transformed to a core-containing product (24 hr, 37 degrees C) which also had 3 apoA-I; this product, however, was smaller (diameter of 8.5 nm) than the product from 3A-I(UC)complexes. Transformation of 3A-I(UC)complexes appeared to result from build-up of core CE directly within the precursor complex. Transformation of 2A-I(UC)complexes, however, followed a stepwise pathway to the product with 3 apoA-I, apparently involving fusion of transforming precursors and release of one apoA-I from the fusion product. In the presence of low density lipoprotein (LDL), used as a source of additional cholesterol, conversion of 2A-I(UC)complexes to the product with 3 apoA-I was more extensive. The transformation product of 3A-I(UC)complexes in the presence of LDL also had 3 apoA-I but was considerably smaller in size (8.6 vs. 9.2 nm, diameter) and had a twofold lower molar content of PC compared with the product formed without LDL. LDL appeared to act both as a donor of UC and an acceptor of PC. Transformation products with 3 apoA-I obtained under the various experimental conditions in the present studies appear to be constrained in core CE content (between 13 to 22 CE per apoA-I; range of 9 CE molecules) but relatively flexible in content of surface PC molecules they can accommodate (between 24 to 49 PC per apoA-I; range of 25 PC molecules). The properties of the core-containing products with 3 apoA-I compare closely with those of the major subpopulation of human plasma HDL in the size range of 8.2-8.8 nm that contains the molecular weight equivalent of 3 apoA-I molecules. PMID- 3112300 TI - Norfloxacin in the treatment of uncomplicated gonorrhoeae in nonpregnant females. PMID- 3112301 TI - Percutaneous endoscopic gastrostomy. PMID- 3112302 TI - Chromatin decondensation and DNA synthesis in human sperm activated in vitro by using Xenopus laevis egg extracts. AB - An in vitro sperm activation system was used to study nuclear swelling-chromatin decondensation and DNA synthesis; processes that occur in vivo following fertilization. Lysolecithin-permeabilized human sperm were incubated in Xenopus laevis egg extract and examined by using phase-contrast light microscopy, electron microscopy, and autoradiography. During a 3-hour incubation, the activated sperm nuclear chromatin underwent a decondensation-recondensation cycle during which DNA was synthesized. This also occurred when egg extract was given a 3-hour preincubation before the addition of the sperm, suggesting that the factor(s) required for initiating the decondensation-recondensation cycle is associated with the sperm. Because both nuclear swelling and DNA synthesis were found to be reproducible and quantifiable, we studied the effect of various agents on the two processes, characterizing the critical component(s) in the egg extract that induces these events. EGTA was found to have no effect on the induced nuclear swelling or DNA synthesis that occurs in the activated sperm. Freezing and thawing the extract or treating the extract with aphidicolin also had no effect on subsequent nuclear swelling; however, the DNA synthesis activity was blocked. Sperm incubated in extract treated with alkaline phosphatase (AP) had both nuclear swelling and DNA synthesis blocked. However, if the sperm were pretreated with DTT, and then incubated with the AP-treated extract, only the DNA synthesis activity of the extract was blocked. When the extract was treated with serine protease inhibitors (PMSF, soybean trypsin inhibitor, or alpha-2 macroglobulin), nuclear swelling occurred; however, DNA synthesis was blocked. These data suggest that phosphoproteins are involved in one or more of the activation events and that a serine protease(s) is involved in the synthesis of DNA. PMID- 3112304 TI - Studies on transmission of human non-A, non-B hepatitis to marmosets. AB - Two sera obtained from four healthy blood donors, which caused non-A, non-B post transfusion hepatitis in two recipients, were experimentally inoculated into nine marmosets. Three of seven marmosets developed acute hepatitis characterized by the elevation of serum concentrations of glutamic pyruvic transaminase (GPT) and/or isocitric dehydrogenase (ICD) 8-11 weeks after inoculation. Four of seven showed histopathological changes of acute hepatitis in liver biopsy specimens during the biochemically acute phase. In electron microscopic examination, attached membrane-like structures, which consisted of two-unit membranes of two neighboring endoplasmic reticula with electron-dense material between them, were noted in cytoplasm of hepatocytes during the acute phase of hepatitis. Furthermore, acute-phase sera obtained from two animals were inoculated into four additional marmosets, and non-A, non-B hepatitis was successfully passaged in two of them. The results of this study indicate that certain species of marmoset monkeys are susceptible to human non-A, non-B hepatitis agents and provide a useful animal model for non-A, non-B hepatitis. PMID- 3112303 TI - Fucosylated glycoconjugates appear on mouse embryos during blastocyst formation. AB - Mouse embryos were analysed for expression of surface glycoconjugates using a panel of fluorescein-labelled lectins. Morulae and blastocysts but not early cleavage stages stained brightly with fucose binding lectins. By contrast, cleavage stages stained brightly with all the other lectins tested. These findings provide evidence for substantial reorganisation of the cell surface during blastocyst formation and are consistent with a role for fucosylated glycoconjugates in compaction. PMID- 3112305 TI - Microbial structures in a patient with sporadic non-A, non-B fulminant hepatitis treated by liver transplantation. AB - Double-shelled virus-like particles (60 nm) and long cytoplasmic tubular structures were found in the cytoplasm of hepatocytes from areas of collapsed and regenerating areas of hepatectomised liver in a 13-year-old boy who received a liver graft for fulminant hepatitis attributed to sporadic non-A, non-B hepatitis. The patient died on the ninth postoperative day from acute graft failure. Although virus-like particles were not found, instead, gram-negative rods were identified in the necrotic graft and the most likely cause of death was a gram-negative septicaemia with a Shwartzman-like reaction localized to the liver. PMID- 3112306 TI - Rat 3-hydroxyanthranilic acid oxygenase: purification from the liver and immunocytochemical localization in the brain. AB - 3-Hydroxyanthranilic acid oxygenase (3HAO; EC 1.13.11.6), the biosynthetic enzyme of the endogenous excitotoxin quinolinic acid, was purified to homogeneity from rat liver and partially purified from rat brain. The pure enzyme is a single subunit protein with a molecular weight of 37-38,000. Kinetic analyses of both pure liver and partially purified brain 3HAO revealed an identical Km of 3 microM for the substrate 3-hydroxyanthranilic acid. Evidence for the identity of liver and brain 3HAO was further provided by physicochemical (electrophoretic behavior, heat sensitivity) and biochemical (pH dependency, activation by Fe2+) means. Antibodies were produced against the pure liver enzyme and the identity of liver and brain 3HAO substantiated immunologically in immunotitration and Ouchterlony double-diffusion experiments. Immunohistochemical studies using purified anti-rat 3HAO antibodies were performed on tissue sections of perfused brains and demonstrated a preferential staining of astroglial cells. Notably, the cellular localization of 3HAO in the brain appears to be in part distinct from that of quinolinic acid phosphoribosyltransferase, the catabolic enzyme of quinolinic acid. Pure rat 3HAO and its antibodies can be expected to constitute useful tools for the further elucidation of the brain's quinolinic acid system. PMID- 3112307 TI - Synaptic vesicle proteins and acetylcholine levels in chick forebrain nuclei are altered by passive avoidance training. AB - In a search for biochemical markers of modified synaptic function following training of day-old chicks on a passive avoidance task, we have assayed two monoclonal antibodies to synaptic vesicle proteins (anti-p65 and anti-SV2) and one raised to postsynaptic densities (411B). We have also measured total acetylcholine (ACh) content. Measurements were made on three forebrain regions known to show metabolic and morphological change consequent on training--the lobus parolfactorius (LPO), paleostriatum augmentatum (PA), and medial hyperstriatum ventrale (MHV)--in the right and left hemispheres 2 and 24 h after training chicks on a passive avoidance task, in which they learn to avoid pecking a bead coated with methylanthranilate [methylanthranilate-trained (M-trained)]. Control chicks were trained on a water-coated bead [water-trained (W-trained)]. Twenty-four hours after training, 411B levels showed no differences between W trained and M-trained chicks in any region. M-training reduced the titre of anti p65 by 16% in the left PA and 15% in the left MHV and that of anti-SV2 by 19% in the left PA. M-trained chicks showed reduced total ACh content in the LPO by up to 40% and in the PA by up to 48% but had no change in ACh level in the MHV. The decreases in antibody titre were not seen in forebrains analysed 2 h after training, but tendencies toward increases in levels in the right PA and MHV were observed with all three antibodies. Significant differences between right and left hemispheric regions, independent of training, were observed for all the antibodies and for ACh content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112308 TI - Increase of catecholamines in mouse brain by systemic administration of gamma glutamyl L-3,4-dihydroxyphenylalanine. AB - We investigated the effect of systemic administration of gamma-glutamyl L-3,4 dihydroxyphenylalanine (gamma-Glu-DOPA) on catecholamine contents in the brain. gamma-Glu-DOPA was transformed to dopamine (DA) in vitro with brain homogenate by the sequential action of gamma-glutamyl transpeptidase and aromatic L-amino acid decarboxylase. Intraperitoneal injection of gamma-Glu-DOPA to mice increased DA markedly and noradrenaline (NA) moderately in the brain. The increase of endogenous DA was followed by elevation of the main DA metabolites (3,4 dihydroxyphenyl-acetic acid and homovanillic acid). These increases were in a dose-dependent manner. The maximal elevation of DA was observed within 30 min after administration of gamma-Glu-DOPA, but a substantial increase of NA was observed 2 h after the administration. These results suggest that gamma-Glu-DOPA may be applicable to the treatment of Parkinson's disease. PMID- 3112309 TI - Phenotypic expression in mucopolysaccharidosis VII. AB - beta-glucuronidase deficiency is an extremely rare disorder which is known to have a considerable phenotypic variation. A survey of the clinical findings in 19 previously reported patients with mucopolysaccharidosis VII is presented together with the results of clinical and biochemical studies in two further patients. Because a similar clinical picture is present in a heterozygotic sister it is doubted whether all signs and symptoms can be attributed to the beta glucuronidase deficiency. The probability of a concomitant disorder is discussed. Diagnosis was made both by demonstration of the deficiency in plasma and leucocytes, and by means of hair root analysis. The phenotypic variation and the fact that increased levels of glycosaminoglycans were not found in the urine of the two patients lead to the suggestion that in certain cases a correct diagnosis may be missed if the beta-glucuronidase activity in plasma and leucocytes is not determined and only routine urine investigation is performed as a screening for a mucopolysaccharidosis. Hair root analysis may be a useful method to measure the beta-glucuronidase activity. PMID- 3112310 TI - Chronic localised encephalitis (Rasmussen's) in an adult with epilepsia partialis continua. AB - A 29 year old male presented with epileptic fits, progressive left sided focal seizures and epilepsia partialis continua, increasing left hemiparesis and mental slowing. Death occurred 2 years after the onset of the illness. Lesions were limited to the right cerebral hemisphere. Hypertrophic astrocytosis was diffuse throughout the gray and white matter but was more severe in the deep cortical layers and U fibres, where it was associated with vacuolar changes and capillary proliferation. Sparse perivascular lymphocytic cuffs, rod shaped microglia and microglial nodules were present. No inclusion bodies were found. These clinico pathologic features were similar to the cases described by Rasmussen. Only five necropsy cases of this rare disease have been reported previously, all in children. The aetiology is unknown. PMID- 3112311 TI - Schistosoma mansoni in the spinal cord: a correlation between operative and radiological findings. PMID- 3112312 TI - Deficient DNA repair in amyotrophic lateral sclerosis cells. AB - We studied survival and DNA repair capacity in cultured sporadic ALS and control skin fibroblasts after treatment with DNA damaging agents producing different types of lesions. Mean survival in ALS and control fibroblasts was similar after exposure to ultraviolet (UV) light, x-rays and mitomycin C (MMC). Both mean survival and mean unscheduled (repair) DNA synthesis (UDS) were significantly reduced in ALS fibroblasts following treatment with the alkylating agent methyl methane sulfonate (MMS). These data suggest that ALS cells are relatively deficient in the repair of alkylation damage, possibly of apurinic/apyrimidinic sites, and that they are not unduly sensitive to DNA damage produced by UV light, x-rays and MMC. Normal survival and UDS seen in some patients' cells after MMS treatment indicate a spectrum of repair efficiency, and suggest heterogeneity of the biochemical defect in ALS. PMID- 3112313 TI - The response of regenerating peripheral neurites to a grafted optic nerve. AB - Optic nerves, both viable (fresh or pre-degenerate) or non-viable (frozen-thawed) were grafted between the proximal and distal stumps of freshly transected sciatic nerves, using either 10/0 sutures or strips of nitrocellulose paper. The majority of regenerating peripheral neurites, always in association with Schwann cells, avoided the viable optic nerve grafts, growing along the outside of the grafts in well vascularized minifascicles until they gained the distal stumps. A very small number of axons entered the grafts and grew, for distances typically less than 2 mm, between layers of astrocyte processes. The number of axons entering was not increased by using predegenerate grafts or by blocking Schwann cell proliferation in the proximal stumps by pre-treating the latter with mitomycin C. There was no evidence of a continuous cellular-acellular partition between graft and host during the outgrowth phase of the neurites: it was concluded that axons failed to enter the grafts as a result of inhibitory interactions between Schwann cells and astrocytes. When grafts were rendered acellular, all structured debris, including recognizable components of the extracellular matrix, was rapidly removed and the space thus vacated was invaded by manifascicles of Schwann cells and regenerating neurites. Glial fibrillary acidic protein-positive astrocytes and carbonic anhydrase II-positive oligodendrocytes persisted within viable grafts for 17 months; they did not migrate into the surrounding nerve. PMID- 3112314 TI - Staining with monoclonal antibodies to neurofilaments distinguishes between subpopulations of neurofibrillary tangles, between groups of axons and between groups of dendrites. AB - A new monoclonal antibody (mab) against neurofilaments is described (mab 1215) and its reactions compared with previously characterized mabs (BF10; RT97). Mab 1215 recognizes an epitope on the heavy neurofilament polypeptide (NF-H). In Alzheimer's disease, mab 1215 recognizes only a subpopulation of neurofibrillary tangles and stains a proportion of tangles in the hippocampus but none of those in the olfactory bulb. However, mabs RT97 and BF10 stain the majority of tangles in both brain areas. Of the three antibodies, only mab BF10 recognizes, specifically, axons of granular cells in the dentate gyrus of the hippocampus. Mab 1215 recognizes more dendrites in the pyramidal layer than either mab BF10 or mab RT97. Our observations indicate that neurofilaments are not identical in all axons and that, contrary to previous reports, NF-H is present in dendrites. The dendritic form of NF-H appears to be different from NF-H in axons and this could be due to differences in the state of phosphorylation of NF-H. We suggest that the finding that distinct subpopulations of tangles exist indicates that tangles are not static lesions. Further investigations into this possibility may illuminate the pathophysiology of Alzheimer's disease. PMID- 3112315 TI - Free light chains in the CSF in multiple sclerosis. AB - The presence of free light chains (FLC) was investigated in 32 patients with clinically definite or laboratory supported definite multiple sclerosis (MS), 2 patients with neurosyphilis and 10 normal controls. The detection of FLC in unconcentrated cerebrospinal fluid (CSF) was performed by means of agarose isoelectric focusing, followed by transfer of proteins to nitrocellulose membranes, double immunofixation, avidin-biotin amplification and peroxidase staining. Bands due to FLC were clearly demonstrated in the CSF of 28 MS patients; 3 of them showed only kappa FLC, 10 only lambda FLC, while 15 had both kappa and lambda FLC. The CSF of 4 MS patients was FLC negative. In both cases of neurosyphilis FLC bands were observed. FLC were never found in normal CSF. Among the indexes of intrathecal immunological activity (IgG oligoclonal bands, FLC, IgG index, intra-blood-brain barrier IgG synthesis rate, pleocytosis) the FLC proved to be the second most frequent abnormality in MS CSF, the presence of IgG oligoclonal bands being the first. In one MS case an FLC band was found, while all the other indexes of intrathecal IgG production were negative. A high correlation was found between an elevated number of FLC and pleocytosis. The presence of FLC in MS CSF seems to indicate a recent immunological stimulation leading to increased synthesis of FLC within the CNS. PMID- 3112317 TI - Capnography and the Bain circuit II: Validation of a computer model. AB - Validation of a computer model is described. The behavior of this model is compared both with mechanical ventilation of a test lung in a laboratory setup that uses a washout method and with manual ventilation. A comparison is also made with results obtained from a volunteer breathing spontaneously through a Bain circuit and with results published in the literature. This computer model is a multisegment representation of the Bain circuit and connecting tubing. For each segment, gas pressure, gas volume flow, and partial pressure of carbon dioxide are calculated for any number of breaths wanted. As a result, the time course of these variables can be generated for any location or, conversely, the carbon dioxide distribution in the system can be calculated for any time instant. A test lung, the human lungs, the ventilator bellows, and the reservoir bag are each represented by a single segment. The shapes of pressure and flow curves and of the capnograms taken at different locations in the Bain tubing are in good agreement. The washout study permits measurement of the time delay between the first expiration and the arrival of carbon dioxide at a particular location. The carbon dioxide level in the test lung decreases during inspiration and is stable during expiration. Quantitative agreement between model and experimental transport delays and carbon dioxide levels is such that the differences can be explained by the inaccuracy of the measurement. This is concluded from a sensitivity analysis. The study of the effect of segment size shows an almost optimal agreement between model behavior and experimental results for a 36 segment model. Execution of a thorough validation is imperative before such models can be used for clinical management and decision making or for teaching. PMID- 3112316 TI - Lupus anticoagulant and cerebral infarction: therapeutic implications. AB - The clinical hematological and radiological findings in a patient with stroke and the lupus anticoagulant are presented, and therapeutic alternatives are reviewed. The importance of recognizing this association is stressed because of its potential therapeutic implications. PMID- 3112318 TI - Now that we have pulse oximeters and capnographs, we don't need precordial and esophageal stethoscopes. AB - One clinician argues that precordial and esophageal stethoscopes are obsolete. Current technology, including pulse oximetry, electrocardiography, and capnography, is both easier to use and more accurate. Another clinician argues that these stethoscopes have an important place in safe patient management. They are an inexpensive but effective extension of the anesthesiologist's own senses. PMID- 3112319 TI - Computer-assisted capnogram analysis. AB - Characteristic abnormal carbon dioxide waveforms from patients with mechanically ventilated lungs are observed when, for example, valves are incompetent, the airway is obstructed, the breathing circuit becomes disconnected, or a patient overrides mechanical ventilation with spontaneous breaths. Automated observation of the carbon dioxide waveform provides a uniform, concise, and consistent interpretation of the capnogram. This article describes a computer algorithm for analyzing and classifying capnograms as normal or as belonging to one of the categories above. The algorithm also generates a diagnostic message when the capnogram deviates from a learned norm for at least three consecutive waveforms (and thus reduces the influence of artifacts). Clinical experience shows reliable waveform recognition by the algorithm. PMID- 3112320 TI - On-line computer estimation of carbon dioxide response curves. PMID- 3112321 TI - Biochemical and immunocytochemical characterization and distribution of phosphorylated and nonphosphorylated subunits of neurofilaments in squid giant axon and stellate ganglion. AB - Monoclonal antibodies to squid neurofilament (aNFP) and intermediate filament (aIFA) proteins were used as probes for the biochemical and immunocytochemical analyses of neurofilament structure and distribution in the squid giant axon and stellate ganglion. On Western blots the aNFP antibody stained exclusively the 220 kDa and high-molecular-weight (HMW) components of neurofilaments in the giant axon, whereas the aIFA antibody primarily labeled the 60 kDa protein in the giant axon and the 60 and 65 kDa proteins in the stellate ganglion. Dephosphorylation of axoplasmic proteins by alkaline phosphatase resulted in a decrease in the molecular weights of both the 220 kDa and HMW neurofilament proteins and a concomitant loss of reactivity with the aNFP antibody on Western blots. This indicated that the aNFP antibody is specific for a phosphorylated epitope in the neurofilament. Increased dephosphorylation of the 220 kDa protein led to an enhanced immunostaining of the resultant 190 kDa polypeptide by the aIFA antibody, suggesting that the phosphorylated epitope may mask the conserved epitope recognized by aIFA. Light and electron microscopic immunocytochemical studies show intense labeling by the aNFP antibody in the giant axon. In contrast, the aIFA antibody labeled the glial cells around the giant axon intensely, while labeling of the giant axon itself was considerably less than that with the aNFP antibody. Since the 60 kDa protein in axoplasm is intensely stained by the aIFA antibody on Western blots, the relatively low amounts of labeling seen on semithin and thin sections of the giant axon by this antibody may be due to the masking of the 60 kDa protein by in situ fixed axoplasmic proteins. However, the aIFA antibody intensely labeled glial cells within the stellate ganglion and "islands" of filaments and nuclear membranes within ganglion cells. No reactivity for either antibody was seen in synapses. The aNFP antibody specifically labeled "beadlike" portions and cross-bridges on the axonal neurofilaments, suggesting that these components consist of the 220 kDa and HMW proteins. In contrast, the aIFA antibody labeled relatively smooth filaments in ganglion and glial cells. These data suggest that the 65 kDa protein represents the squid glial filament protein and that the 60 kDa protein found in axoplasm represents the low-molecular-weight subunit in the axonal neurofilament. The latter appears to be formed and/or organized in "islands" of filaments within ganglion cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3112322 TI - Multiple mechanisms of bursting in a conditional bursting neuron. AB - The anterior burster (AB) neuron in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus, is a conditional burster in the pyloric motor circuit. Bath application of the monoamines dopamine, serotonin, and octopamine induces rhythmic bursting pacemaker potentials in a silent, synaptically isolated AB cell. However, each amine produces a unique and characteristic burst shape, resulting from different ionic dependences of the burst mechanisms. Bursting induced by serotonin or octopamine is critically dependent upon sodium entry through tetrodotoxin-sensitive channels; dopamine-induced bursting is not TTX sensitive. Dopamine-induced bursting is abolished when extracellular calcium is reduced to 25% of normal; serotonin- and octopamine-induced bursts continue in this saline, although they are abolished in salines with calcium reduced to 10% or less of normal. Quantitative differences between the amines are also seen in the tetraethylammonium (TEA) sensitivity of the burst amplitude and in the dependence of the interburst hyperpolarization on extracellular potassium. These experiments demonstrate that there are both quantitative and qualitative differences in the ionic currents underlying every phase of the bursts induced by the 3 amines. Thus, a single neuron can burst via more than one ionic mechanism. PMID- 3112323 TI - Depletion of dopamine in the caudate nucleus but not in nucleus accumbens impairs reaction-time performance in rats. AB - Impairment of the dopaminergic system in the brain induced by dopamine-receptor antagonists or by specific neurotoxin terminal lesions results in motor disturbances in rats. In order to specify further the role of the different dopamine pathways in the brain on motor function, the performance of rats trained in an operant reaction-time task was examined after systemic administration of a dopamine-receptor antagonist, alpha-flupenthixol, and after specific destruction of dopamine neurons by 6-hydroxydopamine perfusion into the nucleus accumbens or caudate nucleus. Rats were trained to press a lever and release it as quickly as possible after a light-cue conditioned stimulus (CS). Reaction time was measured from the CS to the release of the lever for each trial. alpha-Flupenthixol (0.2 and 0.4 mg/kg) injected intraperitoneally impaired the reaction-time performance of the rats. While disruption of dopamine activity in the nucleus accumbens did not affect the performance of the rats, lesions of the dopamine terminals of the nigrostriatal pathway in the corpus striatum (59% decrease in posterior striatal dopamine) significantly impaired reaction-time performance. These results show that moderate decreases in dopamine function restricted to the corpus striatum can disrupt sensitive motor performance, and support the hypothesis that dopamine in the corpus striatum has a role in the initiation of complex goal-directed responses. PMID- 3112324 TI - Dopaminergic mechanisms underlying the reduction of electrical coupling between horizontal cells of the turtle retina induced by d-amphetamine, bicuculline, and veratridine. AB - Previous studies have shown that dopamine, bicuculline, or d-amphetamine reduce the electrical and dye-coupling between the axon terminals of the horizontal cells of the turtle retina (see Piccolino et al., 1984). In the present study we observed similar effects following the application of veratridine. The actions of all these drugs were prevented by dopamine antagonists acting on D1 receptors such as flupenthixol and SCH 23390. However, in contrast to dopamine, the actions of d-amphetamine, bicuculline, and veratridine were attenuated or abolished by pharmacological agents (such as 6-OH-dopamine, alpha-methyl-p-tyrosine, or reserpine) known to reduce the release of dopamine from dopaminergic neurons. Moreover, the actions of veratridine and bicuculline were prevented by tetrodotoxin, indicating that one or more neurons in the dopamine pathway are spike-generating. We conclude that d-amphetamine, bicuculline, and veratridine reduce electrical coupling between the axon terminals of the turtle horizontal cells by promoting the release of endogenous dopamine from the dopaminergic amacrine cells previously identified (Witkovsky et al., 1984). Electron microscopic observations revealed that 6-OH-dopamine selectively attacked this population of amacrine cells. No degenerating terminals were found adjacent to the horizontal cell axon terminals. On this basis, we postulate that dopamine reaches the horizontal cell by diffusion through the extracellular space. PMID- 3112326 TI - Characterization of posttranslational processing of the mammalian high-molecular weight neurofilament protein in vivo. AB - Sensory neurons in the dorsal root ganglion (DRG) were used in an in vivo pulse chase labeling paradigm to examine the time course and nature of posttranslational processing of neurofilament (NF) proteins. Ganglia of adult rats were labeled with 35S-methionine and harvested 1-72 hr later. Samples containing the cell bodies and short initial axonal segments of DRG neurons were analyzed by 1- and 2-dimensional PAGE/fluorography. For comparison, axonally transported NF proteins (200, 145, and 68 kDa) were harvested from the sciatic nerve 21 d after labeling the fifth lumbar (L5) DRG. Analysis of the pulse-chase experiments revealed that the mature 200 kDa protein (NF200) was not identifiable in gels of DRG samples until 24-48 hr after labeling. Immunoblotting/fluorography of 2-dimensional gels with monoclonal antibodies to phosphorylated and unphosphorylated NF proteins identified the high-molecular-weight NF subunit in various stages of processing in the DRG between 1 and 48 hr after labeling. The precursor to NF200 migrated on 2-dimensional PAGE as a 160 kDa protein with a pI of about 7.2. During the next 48 hr, the migration of this protein progressively changed to the mature pattern of 200 kDa and a pI of about 5.2. The 145 and 68 kDa NF proteins exhibited very little change in migration on gels during this same interval. Dephosphorylation of mature NF proteins with E. coli alkaline phosphatase regenerated the 160 kDa precursor, confirming that phosphorylation was the main posttranslational mechanism involved in the maturation of newly synthesized high-molecular-weight NF protein. Detergent extraction of labeled DRGs suggested that the 160 kDa NF protein was present in assembled neurofilaments. Immunohistochemical experiments with monoclonal antibodies were performed to explore the intracellular location of phosphorylated and unphosphorylated high-molecular-weight NF protein. Analysis revealed that neuronal cell bodies, as well as short initial segments of DRG axons located within the ganglion, contained unphosphorylated NF protein, while axons in the distal nerve contained mature, phosphorylated NF200. These findings provide support for a model in which posttranslational processing of the 160 kDa precursor occurs in the initial axonal region of DRG cells after the assembled NFs have left the cell body and begun axonal transport. PMID- 3112325 TI - Transmitter release from presynaptic terminals of electric organ: inhibition by the calcium channel antagonist omega Conus toxin. AB - Cholinergic synaptosomes from electroplax of the ray Ommata discopyge release both ATP and ACh when depolarized with high K+ concentration in the presence of Ca2+. Others have shown that the ATP and ACh are released in the molar ratio found in isolated synaptic vesicles. Thus, it is assumed that the release of ATP reflects exocytosis of synaptic vesicles, and that transmitter release can be indirectly monitored by assaying ATP release. We present further evidence for this assumption and examine the effects of presynaptic neurotoxins on this ATP release. As expected for transmitter release, we find that depolarization-evoked ATP release is supported by Sr2+ and Ba2+ and is inhibited by the Ca channel antagonists Co2+ and Mn2+. Likewise, the presynaptic toxins omega-CmTX and omega CgTX, omega peptides from the venom of the marine snails Conus magus and Conus geographus, respectively, inhibit 80% of the depolarization-evoked ATP release. Half-maximal inhibition of ATP release occurs with approximately 0.5 microM of either toxin. The toxins' effects are reversible, and when toxin is washed away, the time dependence of recovery of release is approximately first order and half complete within 40 min with omega-CmTX and 15 min with omega-CgTX. The Ca2+ ionophore A23187 induces Ca2+-dependent ATP release from resting synaptosomes. As would be expected of a Ca channel antagonist, omega-CmTX does not affect this ionophore-induced release. Leptinotarsin-d (LPTd), a putative Ca channel agonist from the Colorado potato beetle, evokes Ca2+-dependent ATP release from resting synaptosomes. omega-CmTX does not block LPTd-evoked release of ATP, which suggests that omega-CmTX and LPTd act at different sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112327 TI - Cervical spine stenosis secondary to ossification of the posterior longitudinal ligament. AB - Ossification of the posterior longitudinal ligament (OPLL) is a well-documented cause of cervical spine stenosis and myelopathy among Japanese patients. Reports of OPLL in North Americans are rare. Choices of diagnostic method and treatment for this entity remain controversial. The authors report the results of management of 20 patients in the United States with symptomatic OPLL of the cervical spine. These represented 10% to 20% of patients operated on over the last 3 years for myelopathy secondary to structural spinal compression. Most of these OPLL patients were Caucasian (60%), male (male:female 4:1), and middle-aged (median age 47.5 years). Six had previously undergone laminectomy or discectomy. Cervical roentgenograms and standard myelography occasionally suggested the diagnosis. Axial computerized tomography (CT) metrizamide myelography with small interslice intervals proved invaluable for diagnosis and operative planning. Magnetic resonance imaging was not necessary for diagnosis. Retrovertebral calcification extended over one to five bodies (mean 2.75). The mass ranged in size from 5 to 16 mm in anteroposterior diameter and reduced the residual canal diameter to a mean (+/- standard deviation) caliber of 9.42 +/- 2.41 mm (mean narrowing ratio 0.44 +/- 0.12). Anterior cervical decompression by medial corpectomy and discectomy with fusion uniformly reduced preoperative myelopathy. Complications were limited to transient neurological deterioration in two patients, recurrent laryngeal nerve palsy in one, and halo device pin site infections in two. At a mean postoperative interval of 15 months, improvement was seen in each category of deficit: extremity weakness, hypesthesia, hypertonia, and urinary dysfunction. All fusions produced solid unions. It is concluded that OPLL of the cervical spine is an unexpectedly prevalent cause of myelopathy among patients treated in the United States. Thin-section axial CT metrizamide myelography with small interslice intervals is essential for the investigation of patients who may have OPLL. Anterior decompression and stabilization by medial corpectomy, discectomy, removal of the calcified mass, and fusion is a safe and effective method of treatment. PMID- 3112328 TI - Recombinant human tissue-type plasminogen activator therapy in acute thromboembolic stroke. AB - Systemic fibrinolytic therapy for acute stroke is no longer recommended because of resulting systemic fibrinolysis and the risk of intracerebral hemorrhage. Human tissue-type plasminogen activator (TPA) is a native enzyme that converts plasminogen to plasmin with subsequent clot lysis. The affinity for plasminogen is increased several-fold when the substrate is bound to fibrin. At appropriate dosage, "clot-specific" thrombolysis may be achieved at the surface of the thrombus without creating systemic fibrinolysis. The authors designed a study to evaluate the effect of intravenous TPA administered 2 hours after acute thromboembolic stroke in rats. This time course was chosen to simulate an analogous clinical situation. Middle cerebral artery embolic stroke was caused by intracarotid injection of 0.025 cc of human blood clot in 16 rats. Regional cerebral blood flow, measured by the hydrogen clearance technique, and electroencephalographic (EEG) recordings were obtained every 30 minutes for 5 hours after thromboembolism. Eight rats received a 1-hour infusion of intravenous TPA (1.5 mg/kg) 2 hours after injection of emboli. Ipsilateral blood flow increased significantly within 30 minutes after intravenous TPA and reached preembolic levels within 60 minutes. Blood flow did not improve in the eight control rats throughout the experiment. Power spectral analysis of the EEG recordings showed improvement in the treated group compared to the control group. Postmortem angiography revealed proximal middle cerebral artery occlusion in control animals and patent middle cerebral arteries in TPA-treated animals. Serum fibrinogen and fibrin split products were unchanged in both groups, indicating the absence of systemic fibrinolysis. There were no intracerebral hemorrhages. It is concluded that, in this rat model, TPA increases blood flow with subsequent improvement in the EEG recording after thromboembolic stroke without evidence of systemic fibrinolysis. Intravenous TPA may be useful in the treatment of acute stroke in man. PMID- 3112329 TI - Digital angiographic quantification of blood flow dynamics in embolic stroke treated with tissue-type plasminogen activator. AB - Computer analysis of digital subtraction angiography (DSA) was utilized to quantify the effectiveness of tissue-type plasminogen activator (TPA) in a rabbit cerebroembolic stroke model. Fourteen animals underwent cannulation of the facial artery and a preembolus angiogram. Autologous blood clots were then injected, and occlusion of the internal carotid artery at the circle of Willis was documented with repeat angiogram. The experimental group received a 1-mg/kg intravenous infusion of TPA via a femoral catheter for 90 minutes. A control group received an equivalent volume of saline. Follow-up angiograms were performed every 15 minutes. The TPA-treated animals showed progressive improvement in flow through previously occluded vessels. Time-density curves of the contrast material over the middle cerebral artery trunk and brain parenchyma were generated. The best integrated curves for the two groups were compared at 30 minutes after occlusion and 90 minutes after treatment. Animals were then observed for 24 hours and their neurological status was documented. Premortem infusion of either Evans blue dye or neutral red dye was performed and the integrity of the blood-brain barrier and tissue perfusion were assessed by video planometry. Significant improvements were noted by DSA, and Evans blue and neutral red dye studies in animals treated with TPA. PMID- 3112330 TI - ICP reduction with furosemide and mannitol. PMID- 3112331 TI - Clinical evaluation of a thyroxine binding globulin assay in calculating a free thyroxine index in normal, thyroid disease, and sick euthyroid patients. AB - As assay for thyroxine binding globulin (TBG) that measures the thyroxine binding capacity of TBG and other proteins was used to calculate a free thyroxine index (FTI) in 108 consecutive thyroid patients, 2,559 normal patients, and 152 sick euthyroid patients. The TBG assay compared favorably with the triiodothyronine (T3) uptake test in producing a FTI for the clinical evaluation of thyroid patients. In addition, it did not suffer the disadvantages inherent in assays specific for only TBG. In the sick euthyroid population, the TBG assay produced an FTI that was more consistent with the clinical evaluation than did the T3 uptake test. PMID- 3112332 TI - Visualization of right atrial thrombus associated with constrictive pericarditis by indium-111 oxine platelet imaging. AB - A right atrial thrombus is not often seen and only a few reports of visualization have been described. We report a 44-yr-old man who had a large atrial thrombus associated with constrictive pericarditis. Two-dimensional echocardiography and computed tomography showed a large right atrial mass. Indium-111 oxine platelet deposition was demonstrated on the surface of thrombus by platelet imaging. Platelet imaging was useful for differential diagnosis from cardiac tumor, and as an indication for surgical treatment, since right atrial thrombus may have a high risk of pulmonary embolism or severe right heart failure. PMID- 3112333 TI - Toxicity of indium-111 on lymphocytes. PMID- 3112334 TI - Long-term effects of dietary polychlorinated biphenyl and high level of vitamin E on ascorbic acid and lipid metabolism in rats. AB - Long-term feeding of purified diets containing (per kg diet) 100 mg of polychlorinated biphenyl (PCB) and 1000 mg of vitamin E (RRR-alpha-tocopheryl acetate) to male Wistar rats was carried out. Rats fed a diet containing PCB rapidly became hypercholesterolemic and maintained high cholesterol levels throughout the 240 d of the experiment. Rats fed a high dietary level of vitamin E plus PCB had higher serum cholesterol and lower liver cholesterol than rats fed a lower level of vitamin E plus PCB. In rats fed PCB, urinary excretion of ascorbic acid was higher than in rats not fed PCB. Urinary ascorbic acid was lower in rats fed high levels of vitamin E plus PCB than in those fed the normal levels of vitamin E plus PCB. Rats fed PCB had lower liver vitamin A storage and higher vitamin A in kidney than rats not fed PCB. This implies that a redistribution of vitamin A occurred in rats fed PCB. Histological observations revealed that central halves of the hepatic lobules of rats fed PCB showed distinct changes consisting of hypertrophy of hepatocytes in the perivenous region and accumulation of vacuoles (lipid droplets) in the cells in the remaining affected portion. Administration of a high dose of vitamin E could not ameliorate this lesion while the treatment depressed effectively the lipid peroxidation. This suggests that the lipid peroxidation was not responsible for the hepatic damage induced by PCB. PMID- 3112335 TI - Long-term effects on adiposity after preweaning nutritional manipulations in the gastrostomy-reared rat. AB - Male Long-Evans rat pups were either fed by continuous intragastric infusion of a milk formula to match the growth rate of their normally reared siblings, or overfed by continuous infusion of a fat-supplemented formula from d 4 through d 18 postpartum. The early overfeeding accelerated growth and the overfed rats remained significantly heavier than normally reared siblings as adults. Early overfeeding with this procedure led to an adult obesity at 14 mo characterized by significantly larger epididymal and retroperitoneal fat depots resulting from an increase of both fat cell size and number, and by an increase in adipose tissue lipoprotein lipase activity. Gastrostomy rearing per se, without overfeeding, resulted in adult rats that weighed the same as normally reared siblings but had significantly larger retroperitoneal fat depots because of more adipocytes. These findings suggest that the quantity of food consumed during early growth and development, and the quality of early nutrition and/or the early rearing environment affect adipose tissue development and have long-term consequences that persist in the rat. PMID- 3112337 TI - Nine-year follow-up of workers exposed to 1,2-dibromo-3-chloropropane. PMID- 3112336 TI - Effect of enrichment of infusion solutions with branched chain amino acids in parenteral nutrition of rats. AB - The effect of enrichment of the branched chain amino acids (BCAAs) leucine, isoleucine and valine on total parenteral nutrition was studied in rats. Experimental infusion solutions with a sufficient, marginal or deficient level of glucose contained either the conventional amino acid composition (22.6% BCAAs) or a BCAA-enriched amino acid composition (36% BCAAs). Rats were infused with experimental solutions for 4 days and several parameters of protein metabolism were evaluated in various tissues. Under conditions of sufficient energy supply, BCAA-enriched and conventional groups showed similar body weight gains and muscle protein degradations as measured by urinary 3-methylhistidine excretion. Polysome profiles in the liver and gastrocnemius muscle of the BCAA-enriched group were more heavily aggregated than those of the conventional group. Under the conditions of marginal or deficient energy supply, beneficial effects of BCAA enrichment over the conventional amino acid composition became more evident in terms of better body weight retention, higher RNA/DNA ratio and heavier polysome profile in both liver and muscle, and reduced protein catabolism in muscle. The present study suggests that enrichment of BCAAs, particularly valine and isoleucine, may be useful for nutritional support under hypercatabolic or stressed conditions. PMID- 3112338 TI - Acute pulmonary rejection precedes cardiac rejection following heart-lung transplantation in a primate model. AB - Twelve Chacma baboons underwent transplantation of the heart and both lungs from donor baboons matched for size and AB blood group. Cyclosporine was given daily orally, by twice daily intravenous injections, or by a single intravenous injection (together with oral azathioprine and, after 2 weeks, methylprednisolone); whole blood trough levels were inadequate in all groups. Survival was from 4 to 29 days, with death resulting from acute rejection of the lungs in 11 and from bronchopneumonia in one. In the 11 animals dying from rejection, histologic examination showed that the heart was spared from severe rejection in all cases but one. In the inadequately immunosuppressed baboon, therefore, acute rejection occurs earlier in the lungs than in the heart. We have now observed what we believe to have been acute pulmonary rejection in the absence of cardiac rejection on five occasions in three patients in our clinical transplantation program. We would suggest that pulmonary rejection must always be strongly suspected if there are any suggestive features, particularly pulmonary shadowing on chest radiographs, despite negative results of tests indicating rejection of the heart. In the absence of any easy method of confirming pulmonary rejection directly (other than open-lung biopsy, which is clearly contraindicated as a routine procedure), we suggest that more attention should be directed toward developing tests for rejection that are not organ specific, rather than relying on techniques that diagnose cardiac rejection only. PMID- 3112339 TI - Survival following rupture of a pancreatic abscess in a heart transplant recipient. AB - A 43-year-old man underwent orthotopic heart transplantation for end-stage ischemic cardiomyopathy. Immunosuppressive therapy consisted of cyclosporine and corticosteroids. The diagnosis of acute pancreatitis was made on the ninth postoperative day and was based on clinical symptoms and an upper gastrointestinal barium study. Both serum and urine amylase values were normal. Abdominal ultrasound examination was nondiagnostic. Two weeks postoperatively, the patient's clinical condition deteriorated sharply. Chest and abdominal roentgenograms revealed free intraperitoneal air, as well as air in the lesser sac. Diagnosis of a ruptured pancreatic abscess was made, and he underwent immediate exploratory laparotomy. Four liters of purulent fluid were present in the peritoneal cavity. A ruptured pancreatic abscess was found, and it had dissected above the superior mesenteric vessels and down the right gutter over the inferior vena cava. After extensive retroperitoneal debridement and copious irrigation, multiple surgical drains were placed. The patient is now well and is performing normal daily activities 16 months after the transplantation procedure. The incidence and proposed causes of pancreatitis occurring after heart transplant are reviewed, and we discuss our management of this complication. PMID- 3112340 TI - Flush perfusion using Euro-Collins solution vs cooling by means of extracorporeal circulation in heart-lung preservation. AB - Single-flush perfusion using modified Euro-Collins solution and donor cooling by extracorporeal circulation represent two concepts of lung preservation currently in use for on-site heart-lung transplantation. The question of which technique is better for safe clinical application of heart-lung transplantation, including extended periods of ischemia and distant organ procurement, currently remains undetermined. Eighteen mongrel dogs, divided in three groups, underwent left lung, heterotopic heart transplantation, leaving the right lung and heart of the recipient in place. Donor organs were obtained from size-matched dogs. In all groups, myocardial preservation was achieved using 10 ml/kg cold potassium cardioplegia. Following flush perfusion of the lung (Euro-Collins solution, 60 ml/kg), six dogs were immediately transplanted (group I). Using the same preservation, organs were stored for 6 hours at 4 degrees C in group II. In group III, organs were cooled using extracorporeal circulation until reaching a rectal temperature of 16 degrees C, harvested, and thereafter stored as in group II. After transplantation, blood supply of the donor heart was assured by selective drainage of the superior vena cava into the right side of the donor heart. Outflow was obtained by end-to-side anastomosis of donor and recipient aorta. The dogs were kept anesthetized, and both lungs were ventilated selectively with an FiO2 of 0.4 for 20 hours or until death. During the postoperative course, the donor heart pumped about one third of the entire cardiac output in all groups. The lowest pulmonary vascular resistance of the transplanted lung was observed in group III. Oxygenation of the transplanted lung revealed no impairment in group I compared with the pretransplant values. By contrast, groups II and III showed a slight decrease of oxygenation within acceptable limits. We therefore conclude that both methods of cardiopulmonary preservation evaluated may allow for an extended ischemic time of up to 6 hours before heart-lung transplantation. Pulmonary vascular resistance was significantly lower in the group preserved by extracorporeal circulation, possibly reflecting superior preservation of lung function by this method. PMID- 3112341 TI - Heterotopic heart-lung transplantation: a new experimental model. AB - A new method of heterotopic heart-lung transplantation in the rabbit neck is described. Fourteen animals have received transplants with a view to studying the simultaneous histologic changes of early rejection. Seven animals have been treated with cyclosporine; a similar group of seven animals received no immunosuppressive therapy. Cardiac rejection has been characterized by a diffuse infiltrate of mononuclear cells progressing to myocyte necrosis and eventually to global infarction. In the lung the changes of rejection have been reflected especially on the vascular bed, with proliferative endothelial changes involving small- and medium-sized arteries often to the point of occlusion. There has been a striking lack of correlation between the severity of the lesions in the two organs. Prevention of graft rejection by cyclosporine has not been possible because of the susceptibility of rabbits to Pasteurella pneumonia. This new model also holds promise for the evaluation of graft function in acute situations. PMID- 3112342 TI - Successful orthotopic heart-lung transplantation in the baboon after five hours of cold ischemia with cardioplegia and Collins' solution. AB - En bloc transplantation of the heart and lungs was performed in 15 chacma baboons; the donor organs were stored between 4 and 6 hours before transplantation. The hearts were perfused in the donor animals with 15 ml/kg Wicomb's cardioplegic solution at 4 degrees C, the lungs with either 20 ml/kg 4 degrees C Collins' solution with an added 2.5% dextrose and 12 mEq magnesium sulfate (Collins' solution, group 1, n = 8), Collins' solution plus superoxide dismutase (40,000 U/L superoxide dismutase, group 2, n = 4), or Collins' solution plus superoxide dismutase plus peroxidase (5000 U/L peroxidase plus mannitol, group 3, n = 3). The pulmonary artery perfusion pressure was not allowed to exceed 50 cm water; the lungs were maintained at 30% to 50% inflation, and external cooling was applied. After explantation the thoracic organs were stored in 0.9% saline solution at 4 degrees C. In groups 1 (Collins' solution) and 2 (Collins' plus superoxide dismutase) all surviving baboons revealed normal blood gas values and normal light and electron microscopic histology at 24 hours. Three animals had further biopsies at intervals between 1 and 9 days, at which time the histology of the lungs proved normal and well preserved. All three baboons in group 3 (Collins' plus superoxide dismutase plus peroxidase) had grossly abnormal blood gas values from the time of operation, and all died within 9 hours; light microscopy of the lungs showed early lung infarctlike lesions and in one case pulmonary edema. These preclinical findings proved that storage of the lungs in Collins' solution with or without superoxide dismutase is possible for up to 5 hours; the addition of peroxidase had a detrimental effect. PMID- 3112343 TI - Effect of simultaneous lung transplantation on heart transplant survival in rats. AB - Clinical observations in humans reveal that heart-lung transplant recipients suffer significantly less cardiac rejection than those receiving only heart transplants. A heterotopic combined heart-lung model in rats was used to test the hypothesis that the presence of the lung in this combination increases survival of the heart transplant. Cardiac survival was compared between en bloc heart-lung transplants and heart transplants. Low dosages of cyclosporine were used to prolong but not prevent the rejection process. Heart graft survival in the cyclosporine, 1 mg/kg/day, groups was significantly prolonged in heart-lung allografts. Histologic studies also demonstrated more advanced rejection of the heart in the heart-only transplant groups as compared with the heart-lung transplant groups. This study shows that the presence of the lungs in heart-lung allografts provides for prolongation of cardiac survival. PMID- 3112344 TI - Evolution of hemodynamics after orthotopic heart and heart-lung transplantation: early restrictive patterns persisting in occult fashion. AB - Though successfully transplanted hearts respond in such a way that individuals remain remarkably asymptomatic, they do not function normally. Characterization of early hemodynamic patterns and their evolvement has not been done. The evolution of hemodynamic indices in 20 patients receiving orthotopic heart (n = 17) or combined heart-lung (n = 3) transplants is therefore documented. In 15 isolated heart recipients, right heart catheterization was performed at 24 to 48 hours, 1 to 2 weeks, 4 to 8 weeks, and greater than 3 months after surgery at the time of routine endomyocardial biopsy. Early, patients had elevated mean blood pressure (96 +/- 14 mm Hg, mean +/- standard deviation), mean right atrial pressure (15 +/- 6 mm Hg), right ventricular end-diastolic pressure (16 +/- 7 mm Hg), mean pulmonary artery pressure (30 +/- 7 mm Hg), and mean pulmonary capillary wedge pressure (19 +/- 6 mm Hg), but normal resting heart rate (96 +/- 14 beats/min) and cardiac output (5.6 +/- 1.6 L/min). Heart rate, blood pressure, and output did not change during follow-up, but right atrial pressure decreased dramatically (4 +/- 2 mm Hg at 3 months), as did right ventricular end-diastolic pressure (4 +/- 4 mm Hg), mean pulmonary artery pressure (21 +/- 8 mm Hg), and pulmonary capillary wedge pressure (11 +/- 4 mm Hg). Analysis of right heart filling dynamics revealed an abnormal inspiratory rise in mean right atrial pressure (15 +/- 6 and 27 +/- 7 mm Hg at 24 to 48 hours) that subsequently resolved. In eight patients whose resting follow-up right heart pressures normalized, rapid volume challenge uncovered occult restrictive right atrial pressure patterns that increased from 4 +/- 4 to 9 +/- 4 mm Hg after infusion of saline solution. Kussmaul's response was not apparent with prevolume infusion, but volume expansion caused appearance of this hemodynamic pattern. All patients had early evidence of tricuspid insufficiency, but in two patients, the Doppler regurgitant fraction was over 50%. These two individuals had hemodynamics similar to the other 15 patients initially, but in contrast, their right heart filling pressures did not change during follow-up. Other significant echocardiographic findings included enlarged atria and increased left ventricular mass in all patients. In two of three combined heart-lung transplant patients, similar hemodynamic patterns were evident. Rejection indices did not correlate with hemodynamic observations. Thus a characteristic evolvement of hemodynamics in heart and heart-lung transplants that mimic dynamics associated with restrictive myocardial disease is documented.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3112345 TI - Congenital oral juvenile xanthogranuloma: report of a case. PMID- 3112346 TI - A case of IgG lambda-type solitary plasmacytoma in the maxilla associated with amyloidosis. PMID- 3112348 TI - Mucocutaneous granulocytic sarcomas of the head and neck. AB - Granulocytic sarcomas are malignant solid tumors composed of poorly differentiated myeloid cells that occur in association with myelocytic leukemia. The clinicopathologic characteristics of granulocytic sarcomas that presented in the oral mucosa and in the facial, scalp and neck skin of 8 patients in the acute phase of myelocytic leukemia are described and discussed. Although most of the tumors were demonstrably sensitive to cytosine arabinoside, alone or in combination with other antineoplastic drugs, the prognostic portent of these lesions was extremely poor. PMID- 3112347 TI - Absence of circulating IgG immune complexes in minor recurrent aphthous ulceration. AB - A monoclonal rheumatoid factor binding assay has been employed to detect IgG type immune complexes in sera from 21 patients with minor recurrent aphthous ulceration and 31 control subjects. In only one of the ulcer group patients was there a marginal elevation of immune complexes above the normal range, with no statistically significant difference between the patient and control groups. Assays of intrinsic serum rheumatoid factor and serum IgG, IgM and IgA levels also showed no significant differences between patient and control groups, with all mean values falling within the normal ranges. PMID- 3112349 TI - Extent and diversity of inflammatory cell infiltrates in squamous cell carcinomas and basal cell epitheliomas of the head and neck. AB - Using monoclonal antibodies reactive with Langerhans' cells (LCs), macrophages, and T cell subpopulations, the density and proportions of cells of the immune system of the normal oral mucosa were determined immunohistochemically, and compared with findings in oral squamous cell carcinomas (SCC) and basal cell epitheliomas (BCE). In normal oral epithelia, the dominant cell type was the LC, positive for CD 1, and expressing HLA-DR antigens (DR+). Many intraepithelial cells were lymphocytes of the suppressor/cytotoxic phenotype (CD 8+), which was also the most prominent cell type in the normal mucosal stroma. Significant differences were observed for the content of CD 8-, OKM 1-, and CD 4-positive cells in the epithelium of normal oral mucosa, SCC, and BCE, and for the amount of CD 1-positive Langerhans cells in the connective tissue of the different groups of tissues. When CD 4/CD 8 ratios were calculated, differences between SCC and BCE became most evident. A CD 4/CD 8 ratio greater 0.5 was seen to be characteristic for BCE. Thus, in contrast to the striking preponderance of suppressor/cytotoxic lymphocytes (CD 8+) in SCC, BCE showed typically almost balanced numbers of suppressor/cytotoxic (CD 8+) and helper/inducer (CD 4+) lymphocytes. This finding further underlines the biological differences recognized between these most common neoplasias of the head and neck. PMID- 3112350 TI - Alterations in lipid fluidity induced by cholesterol and cholesterol hemisuccinate modulate the organization of microtubule skeletons in epithelial cells. AB - This study was designed to evaluate the role that cholesterol, and the more hydrophilic ester, cholesterol hemisuccinate (CHS) have on the ability of epithelial cells to attach, spread and reorganize microtubule skeletons on a defined substratum. A431 carcinoma cells were grown and incubated with cholesterol, or CHS in polyvinyl pyrrolidone. Subsequently the cells were plated either on plastic petri dishes or plasticware coated with collagen IV or laminin. The alteration in apparent membrane microviscosity was ascertained using fluorescence polarization measurements. Organization of microtubules was determined by immunofluorescence, and by transmission electron microscopy. Cholesterol and CHS inhibited attachment and spreading of epithelial cells. Cells previously attached and spread became spherical after treatment with cholesterol and CHS, but microtubules were unaffected. However, when the cells were pretreated in suspension with cholesterol or CHS the membrane microviscosities markedly increased, and upon subsequent plating those cells adhering neither spread nor organized microtubule skeletons. These results suggest that cholesterol-induced changes in lipid microviscosity modulate the membrane dynamics that control the ability of epithelial cells to attach, spread and organize microtubule skeletons. PMID- 3112351 TI - The application of microspectrocytofluorometric measurement of Feulgen nuclear DNA content in experimental tumors of rat submandibular gland, 2. The correlation between proliferative ability and nuclear DNA content of tumor tissue in autotransplanted areas. AB - We have reported that there is a difference in the variation of the nuclear DNA content of tumor cells among cases of squamous cell carcinoma induced by 9,10 dimethyl-1,2-benzanthracene (DMBA) in the rat submandibular gland. In the present investigation, the relationship between the nuclear DNA content of tumor cells in autotransplanted sections collected from primary lesions of DMBA-induced tumors and their proliferative ability in the subfascial area of the rat abdomen was examined. As a result of autotransplantation, proliferation in the autotransplanted area was observed in 6 of 14 (42.8%) cases of autotransplantation. Five of these had a keratinizing squamous cell carcinoma while the remaining one had a sarcomatoid tumor. The histological type of the tumor of the proliferative lesion in the transplanted area was very similar to that of the tumor tissues in the primary lesion or the transplanted section collected from the primary lesions. In the proliferative group, marked variation of the nuclear DNA content was observed in the tumor cells of the transplanted section. The proliferative index (PI) was high for these tumor cells in this group. There was no variation in the nuclear DNA content in the tumor cells of the nonproliferative group, and the PI was also low. These results were considered to suggest that there was a correlation between the nuclear DNA content of these experimental tumor cell and their proliferative ability in the autotransplanted area. Therefore, the determination of nuclear DNA content by this method can be used as an objective index of the proliferative ability of tumor tissue. PMID- 3112352 TI - Differences in mucosal reaction related to Candida albicans isolates. AB - In order to examine the behavior of Candida albicans in an oral mucosal model, 16 isolates of the organism were collected from a variety of clinical settings and were inoculated weekly, in equal numbers and concentrations, into the mouths of separate groups of 20 female Sprague-Dawley rats. Oral swabs were taken bi-weekly in order to monitor the presence of the yeast. After 16 weeks, the animals were killed and the tongues were examined grossly and histologically. Six isolates demonstrated the ability to produce characteristic dorsal tongue lesions to varying degrees (1/20; 1/20; 1/20; 2/20; 3/20; and 12/20). Of the remaining 10 isolates, 5 showed hyphal penetration of the keratin layer of the dorsal tongue epithelium, yet no mucosal reaction was elicited and no lesion was produced (1/19; 2/19; 4/20; 5/20 and 5/20). These findings support the concept that C. albicans exhibits a spectrum of mucosal pathogenicity for dorsal rat tongue. PMID- 3112353 TI - The expression of Ultrabithorax (Ubx) during development of the nervous system of Drosophila. AB - Using a double-staining technique with the neuron-specific monoclonal antibody 22C10 and the anti-Ubx monoclonal antibody FP 3-38 we describe the development of landmark cells in the nervous system of Drosophila. The staining with MAb 22C10 provides an internal system of reference that allows a precise localization of the most prominent Ubx active cells. The expression of Ubx seems to initiate at the segmental border in the hypoderm and the homologous region in the neuromeres. Also, the extent of Ubx expression follows quantitative and qualitative changes during embryonic development. PMID- 3112354 TI - Genes in subdivision 1B of the Drosophila melanogaster X-chromosome and their influence on neural development. AB - Genes within subdivision 1B of the X-chromosome of Drosophila melanogaster are known to affect the development of both the central (CNS) and the peripheral (PNS) embryonic nervous system. In this paper we describe the phenotypes of embryos hemizygous for terminal and interstitial deletions of region 1B1-1B10, and of embryos carrying different mutations in certain genes of this region. A minimum of 6 genetic functions that are involved in neural development can be defined in this region. Three of these genes, mapping to the l'sc(a gene of the achaete-scute complex, ASC),elav and vnd loci, affect major and apparently different aspects of CNS development. Two additional genes of the ASC, ac and sc alpha, also play a role in CNS development, although their participation can only be demonstrated under certain conditions. Finally, in the rightmost part of the region uncovered by the deletion Df(1)260.1, two not yet well separated functions are found to be required for embryonic CNS and compound eye development, respectively. Of these two functions, the embryonic one is similar to the ones of ac and sc alpha, and can therefore be considered as a new element of the ASC. PMID- 3112355 TI - Prognosis in fetal valproate syndrome. PMID- 3112356 TI - Evaluation of factors in high risk neonatal necrotizing enterocolitis. AB - Fifty-four neonates with necrotizing enterocolitis (NEC) were separated on basis of outcome. Of 35 factors compared between a high-risk and a low-risk group, only six were found to be statistically significant and useful in the development of a NEC score: number of days before beginning enteral feedings; blood pH; serum bicarbonate concentration; white blood cell differential; abdominal tenderness; and presence of portal vein gas. All laboratory values and physical and radiographic findings were from the initial presentation of NEC. Neonates with a score of 3 or more are at an increased risk of developing severe NEC with a greater than 50% mortality. The study suggests that enteral feedings should be withheld from neonates at risk of developing NEC for the first 12 days of life. PMID- 3112357 TI - The safety and cost-effectiveness of polyethylene glycol electrolyte solution bowel preparation in infants and children. AB - Golytely, a polyethylene glycol electrolyte solution (Braintree Laboratories, Braintree, MA), was evaluated in the preoperative bowel preparation of 21 infants and children. Weight, temperature, pulse, respiratory rate, and electrolyte concentrations were documented before and after mechanical bowel preparation. All children were given 25 mL/kg/h of Golytely until rectal effluent was clear and free of particulate matter. All preparations were started and completed the afternoon prior to surgery. Weight, vital signs, and electrolyte concentrations did not change significantly. All preparations were felt to be fair or excellent. Follow-up for 1 month postoperatively revealed no infectious complications. Golytely is safe and effective in preparing the bowel prior to surgery in children. Using Golytely can eliminate the need for multiple-day hospitalizations for bowel preparation and thus decrease the cost of medical care. PMID- 3112358 TI - Transduodenal feedings: a superior route of enteral nutrition. AB - Our recent study comparing gastric with jejunal feedings in neonatal piglets demonstrated better weight gain, less diarrhea, and less fat malabsorption in animals fed gastrically. These differences were postulated to be due either to loss of duodenal osmoregulation and absorption, and/or to loss of the combined effects of salivary enzymes, gastric emptying, and gastric secretions on jejunal feedings. The objective of this investigation was to determine the relative contributions of gastric and duodenal function to the differences between gastric and jejunal feedings. Seven piglets (3 to 5 days old, 1.5 to 2.0 kg) underwent operative transgastric insertion of a duodenostomy tube placed just distal to the pylorus. Intravenous fluids and antibiotics were administered for two days postoperatively, then Premature Enfamil Formula (24 kcal/oz; Mead Johnson, Evansville, IN) was administered continuously through the feeding tube. The animals were maintained on 115 kcal/kg/d as in the previous study. Weight, fecal fat analysis, and stool characteristics were determined throughout the 2-week period. The resulting data were compared with data from our previous study comparing gastric with jejunal feedings. These data suggest the vital importance of gastroduodenal contributions of absorption, osmoregulation, and regulation of nutrient concentrations in improving the nutritional status of experimental animals. Duodenal feedings may be preferred to either gastric or jejunal feedings because they provide equivalent nutritional support without the gastroesophageal reflux and aspiration reported with gastric feedings in the neonatal population. PMID- 3112359 TI - Total parenteral nutrition and intestinal development: a neonatal model. AB - Total parenteral nutrition (TPN) is widely used in premature and/or surgical neonates, but there is little information available about its effects on intestinal growth and development. Adult TPN models have demonstrated mucosal atrophy, and a young piglet model showed similar but increased intestinal hypotrophy. We have investigated these effects in the neonatal piglet model. Five three-day old piglets received a glucose (40 g/kg/d), amino acid (8 g/kg/d), and fat (4 g/kg/d) solution intravenously for 3 weeks. Matched littermates were fed an artificial sow-milk formula enterally at an equivalent caloric rate (215 kcal/kg/d). A third littermate was sow breast fed for the same study period. No differences were seen in the TPN or formula-fed piglets in weight gain (31 to 34 g/kg/d), hematocrit (25% to 27%), BUN (12 to 13 mg/dL), total serum protein (4.1 to 4.4 g/dL), or total bilirubin (0.4 to 0.6 mg/dL); however, the TPN animals were mildly hyperglycemic (167 mg/dL). The sow-fed control group had greater weight gain (51 g/kg/d) but were without caloric restriction. There were significant decreases in weight and length of the gastrointestinal tract, particularly in the proximal small bowel of the TPN piglets. Compared with formula piglets or sow-fed controls, the TPN proximal small bowel weight was reduced by 67% and 72%, respectively. Similar but less marked differences were seen in the TPN distal small bowel. There were no significant differences in the proximal or distal small bowel measurements between the formula and sow-fed piglets, despite their differences in overall weight gain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112360 TI - Changes in the body composition of the surgical infant in the early postoperative period. AB - The purpose of this study was to evaluate the effects of postoperative nutritional management on the body composition of infants after major surgery. We studied 13 full-term surgical infants (mean initial weight 2.88 +/- 0.19 kg; mean days postsurgery 5.0 +/- 0.5). Ten infants were receiving total parenteral nutrition and three were orally fed (mean caloric intake 84 +/- 4 kcal/kg/d; mean fluid intake 145 +/- 4 mL/kg/d). Total body water (TBW) was measured by isotope dilution using heavy oxygen (18O) labeled water (H2(18)O). Total body fat (TBF) was estimated from anthropometric data. Lean body mass (LBM) was calculated as follows: LBM = weight--TBF. Protein, fat, and carbohydrate accretion were determined by energy and macronutrient balance in conjunction with open-circuit indirect calorimetry. Body composition was reevaluated after an interval of seven days. Body weight increased from 2.88 +/- 0.19 to 3.00 +/- 0.19 kg, representing a mean growth velocity of 5.9 g/kg/d. Increments were observed in all body compartments but only the increase in TBF reached statistic significance (12.9 v 14% of body weight, P less than .05). TBW ranged from an initial value of 76.2 +/ 1.4% to a value of 75.5 +/- 1.4% at the end of the study. Protein, fat, and carbohydrate accretion (g/kg/d) during the seven-day study period were 1.62 +/- 0.13; 1.44 +/- 0.41, and 0.96 +/- 0.70, respectively. These data indicate that in the early postoperative period, the weight gain is secondary to both water and solid tissue accretion. Fat represents the major form of energy storage in the new tissues synthesized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112361 TI - Spontaneous resolution of acid gastric injury. AB - While alkali ingestion nearly always injures the esophagus, acid usually spares the esophagus and damages the gastric outlet. Most reported cases of acid gastric injury have required resection. We report a case of acid ingestion managed with parenteral nutrition and histamine blockers in which healing is documented without operation. PMID- 3112363 TI - Serum albumin (oncotic pressure) correlates with enteral feeding tolerance in the pediatric surgical patient. AB - The influence of serum oncotic pressure (Serum Albumin [SA]) on gastrointestinal (GI) tolerance of enteral feedings was prospectively studied in two phases. Phase I consisted of 46 patients, aged 3 months to 12 years, (mean 47 months) selected for enteral tube feeding via the stomach or small bowel. Twenty-eight patients had an SA greater than 3.0 g/dL and received 82% of predicted caloric and protein needs. Administration of the enteral diet was stopped for two or more days in four of the 28 patients because of GI intolerance. Eighteen patients had an SA less than 3.0 g/dL and received 51% of predicted protein needs. Ten of the 18 patients had diet intolerance for two or more days, (P less than .001). Student's t-test was used for data analysis. In phase II, 20 patients, aged 4 months to 14 years (mean 49 months), with an SA less than 3.0 g/dL underwent repletion with salt poor albumin as calculated by the following formula: Albumin Replacement = [3.5 g/dL--Serum Albumin (g/dL)] X [weight (kg) X 3] Mean prereplacement SA was 2.31 g/dL; immediately after replacement it was 3.43 g/dL, and 1 week later it was 3.41 g/dL. These patients received 87% of predicted calories and nitrogen and only two of 20 had diet intolerance for two or more days. These data suggest that correction of SA levels allows for better tolerance of enteral diets and that SA will remain normal after intravenous replacement if adequate nutrients are provided while correcting the SA. PMID- 3112362 TI - Parenteral nutrition with associated cholelithiasis: another iatrogenic disease of infants and children. AB - During the past decade, 246 infants and children treated at the Columbus Children's Hospital have required more than 4 weeks of parenteral nutrition (PN). Of the 178 survivors, 70 returned for evaluation. Sixty-eight either had adequate visualization of the gallbladder by ultrasound or had previous gallbladder surgery (39%). Of 68 children who did not survive, complete postmortem examinations or ultrasound studies were available for 16 (24%). A diagnosis of cholelithiasis was established in 11 of the 84 studied patients (13%). Six of these children (55%) have required cholecystectomy for relief of chronic abdominal pain, pancreatitis, or empyema of the gallbladder. One additional infant underwent cholecystostomy. Two of the four remaining patients are asymptomatic, one has episodes of abdominal colic, and one child expired of chronic hepatic insufficiency as a result of PN-associated cholestasis. Risk factors that predisposed these children to cholelithiasis included short bowel syndrome, lack of an ileocecal valve, and an increased number of abdominal operative procedures (P less than .05). Patients with biliary calculi also had a longer duration of parenteral feeding, and a higher incidence of both PN associated cholestasis and necrotizing enterocolitis. The intergroup differences for these characteristics, however, did not achieve statistical significance. On the basis of this information, routine ultrasound examinations of the gallbladder are recommended for children maintained on PN for longer than 30 days. All patients presenting with abdominal pain who previously received PN should also be evaluated. Early elective cholecystectomy is suggested for children who develop PN-associated cholelithiasis. PMID- 3112364 TI - Use of a subclavian venous catheter for short- and long-term hemodialysis in children. AB - Vascular access for hemodialysis in children poses problems not encountered in adults because of the small size of the vessels available. The increasing use of peritoneal dialysis has created a large number of patients who need prompt access for hemodialysis for days to weeks during episodes of peritonitis. There are also occasional patients who have exhausted available fistula sites and still require hemodialysis. To address these problems, we designed a series of catheters for insertion in the subclavian vein. The catheters are stiffer than the Hickman type catheter to allow for higher flow rates without collapse. Seventy-five catheters were implanted in 58 patients with a mean age of 14 years. Twelve catheters were inserted in ten children for long-term (over 3 months) access; they have been in place for a mean of 259 days and used for a mean of 64 dialyses. In two children, the catheter has been the sole site for hemodialysis for over a year. Fifty-eight catheters were implanted in 43 patients for short-term hemodialysis. They were in place for a mean of 29 days and used for a mean of 13 dialyses. The major complications encountered were clotting of the catheter and migration out of position. Four catheters were removed because of infection. These new catheters provide effective hemodialysis for children as small as 7 kg with an acceptable morbidity rate and may be used for extended periods of time if necessary. PMID- 3112365 TI - Effects of N-ethylmaleimide on arginine vasopressin-induced responses in an established smooth muscle cell line. AB - We have previously reported that 8-arginine vasopressin (AVP) stimulates phosphatidylinositol turnover and Ca++ mobilization in rat aortic smooth muscle cells (A10). In the present study, N-ethylmaleimide (NEM) was used to further characterize the putative guanine nucleotide binding protein that transduces the V1 receptor effects on phosphatidylinositol turnover and Ca++ efflux in these cells. Pretreatment of the cells with low concentrations of NEM did not affect the basal levels of the inositol phosphates and Ca++ efflux but significantly inhibited the AVP-induced increases. NEM pretreatment did not significantly affect [3H]AVP binding to intact cells. Guanyl-5'-yl imidodiphosphate reduced the apparent binding affinity of AVP to cell membranes. NEM pretreatment abolished this guanyl-5'-yl imidodiphosphate effect. AVP stimulated a specific GTPase activity in cell membranes; this effect was also abolished by NEM pretreatment. The results suggest that in A10 cells a guanine nucleotide binding protein sensitive to NEM couples vasopressin receptors to phospholipase C. PMID- 3112366 TI - Lidocaine and indocyanine green kinetics: effect of hypoxemia and/or hypercapnia. AB - Patients with premature ventricular contractions are also frequently hypoxemic (HO) and/or hypercapnic (HC). The aims of the present study were to document the effect of HO and/or HC on the kinetics of lidocaine, a first choice drug for the i.v. treatment of premature ventricular contractions, and on indocyanine green (ICG), another flow-dependent drug. For this purpose, five groups of rabbits were used: a control group received 2.5 mg/kg i.v. of ICG followed, 30 min later, by 7.5 mg/kg of lidocaine as a bolus. Four other groups received lidocaine as an infusion (261 micrograms/min/kg) for 255 min and ICG (249 micrograms/min/kg) for 8 min, the latter beginning 180 min after the start of the lidocaine infusion. The controls and one test group receiving the lidocaine infusion were breathing air (PaO2 = 89 +/- 2 (S.E.M.) and PaCO2 = 20 +/- 1 mm Hg); the second test group had HO (PaO2 = 51 +/- 1 mm Hg), a third group HC (PaO2 = 68 +/- 1 mm Hg) and the fourth HO combined with HC (HOHC) (PaO2 = 53 +/- 1 and PaCO2 = 61 +/- 2 mm Hg). Multiple blood samples were drawn. Lidocaine and its metabolites and ICG were assayed by high-performance liquid chromatography. Lidocaine volume of distribution was not affected by HO and/or HC. Compared to control values, the clearance of infused lidocaine (CIL) tended to decrease from 65 +/- 2 to 53 +/- 3 ml/min/kg. In animals with HO, HC and HOHC, CIL was 49 +/- 6, 45 +/- 5 and 46 +/- 3 ml/min/kg, respectively, these values not being significantly different from CIL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112367 TI - Effects of L-threo-3,4-dihydroxyphenylserine on efflux of monoamines and acetylcholine in guinea pig brain. AB - The effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on the release of monoamines and acetylcholine (ACh) was studied in the superfused brain slices of guinea pig. In the tissues preloaded either with [3H]norepinephrine ([3H]NE), [3H]dopamine ([3H]DA), [3H]-5-hydroxytryptamine or [3H]choline, tritium effluxes were estimated in serial fractions of superfusates. L-threo-DOPS produced a concentration-dependent increase in the spontaneous efflux of [3H]NE both in the cortical and hypothalamic slices and to a lesser extent that of [3H]DA in the striatal slices. These effects were still fully detected when slices were superfused with a calcium-free medium or tetrodotoxin (10(-6) M). Carbidopa at 5 X 10(-4) M but not at 10(-4) M significantly depressed the [3H]catecholamine effluxes induced by L-threo-DOPS. L-threo-DOPS produced a minimum increase in the spontaneous efflux of [3H]-5-hydroxytryptamine but not that of [3H]ACh. L-threo DOPS (5 X 10(-4) M) significantly reduced the [3H]ACh efflux from electrically stimulated striatal slices and this effect was antagonized by an alpha-2 adrenoceptor antagonist yohimbine (10(-6) M) or by a D2 DA receptor antagonist sulpiride (10(-6) M). In vivo, L-threo-DOPS (150 mg/kg i.p.) produced a gradual but long-lasting increase in the efflux of [3H]NE from the parietal cortex of the guinea pig pretreated with carbidopa (20 mg/kg i.p.). In the brain homogenates, L threo-DOPS (10(-10) to 10(-4) M) itself did not inhibit the bindings of [3H]rauwolscine or [3H]spiperone, specific ligands for labeling alpha-2 and D2 receptors, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112368 TI - Differential influence of calcium channel-blockers on prostanoid generation and thromboxane-mediated vasoconstriction in rabbit lungs. AB - In blood-free perfused and ventilated rabbit lungs, the influence of calcium channel-blockers on pulmonary prostanoid generation and thromboxane-mediated vasoconstriction was investigated. The specific pathways of arachidonic acid (AA) metabolism were stimulated by repetitive pulmonary artery injection of the calcium-ionophore A 23187, which induces the liberation of endogenous AA, or by repetitive application of exogenous AA. In control lungs, both stimuli provoked reproducible phasic vascular pressor responses, accompanied by the release of thromboxane A2 and prostaglandin I2 into the perfusion fluid. Repeated stimulus application in the presence of increasing concentrations of different calcium antagonists showed a dose-dependent inhibition of the pressor responses by all agents. The rank order of potency was nimodipin greater than LU-40883 (verapamil derivative) greater than diltiazem and D-888 (verapamil derivative) greater than verapamil for the ionophore-induced pressure increase, whereas diltiazem was nearly ineffective in the presence of exogenously applied AA. The prostanoid release after application of A 23187 was influenced differentially by the calcium channel-blockers. It was not affected by nimodipin and verapamil, it was slightly depressed by the verapamil derivatives D-888 and LU-40883 and it was dose dependently and in higher concentrations nearly inhibited completely by diltiazem. We conclude that the thromboxane-mediated pulmonary vasoconstriction is inhibited by different-type calcium channel-blockers with a marked rank order of potency. The prostanoid generation induced by stimulation of the lung vascular AA metabolism is influenced differentially by these agents. PMID- 3112369 TI - Injury to rat hearts produced by an exogenous free radical generating system. Study into the role of arachidonic acid and eicosanoids. AB - This study was designed to evaluate the effect of an exogenous free radical generating system consisting of purine plus xanthine oxidase on the isolated rat heart and in particular to assess the possible contribution of arachidonic acid or its metabolites to toxicity produced by this drug combination. Purine plus xanthine oxidase produced a time-dependent depression in cardiac contractility which was associated with stimulated release of lactate dehydrogenase (LDH). Electron microscopic analysis revealed a distinct separation of the glycocalyx from the sarcolemmal membrane with no apparent intracellular defects. Purine plus xanthine oxidase was a potent stimulus for 6-keto-prostaglandin F1 alpha (6K-PGF1 alpha) synthesis but leukotriene production was undetectable under any condition. Eicosatetraynoic acid, which totally prevents the metabolism of arachidonic acid, accelerated the loss in force and increased LDH release invoked by purine plus xanthine oxidase, but produced no noticeable change in sarcolemmal ultrastructure. Cyclooxygenase inhibitors produced little influence although pretreatment with either acetylsalicylic acid or ibuprofen decreased contractility toward the end of purine plus xanthine oxidase perfusion. Nordihydroguarietic acid, a purported inhibitor of 5'-lipoxygenase accelerated the loss in force produced by purine plus xanthine oxidase. The nordihydroguarietic acid effects were associated with reduced 6K-PGF1 alpha efflux but LDH release was unaffected. We also examined whether modification of arachidonic acid release through changes in calcium concentration was associated with altered response to purine plus xanthine oxidase. Lowering the calcium concentration to 0.41 mM (from 1.25 mM control) reduced markedly 6K-PGF1 alpha, efflux as well as LDH release. Although the latter is suggestive of protection, hypocalcemic perfusion resulted in a greater loss in force due to free radical generation. Furthermore, cells from these hearts exhibited a greater degree of glycocalyx separation. Increasing the calcium concentration to 2.50 mM produced no further toxic manifestations in the response to purine plus xanthine oxidase, although the release of 6K-PGF1 alpha was increased. Our results suggest complex toxicity induced by an exogenously generated free radical system. The injury produced by this method is restricted to sarcolemmal changes, the latter being dependent on the external calcium concentration. The study further suggests that accumulation of intracellular unesterified arachidonic acid, which may result from peroxidation of membrane lipids, increases tissue injury caused by exogenous free radicals. PMID- 3112371 TI - The effect of small changes in arterial carbon dioxide tension on carotid chemoreceptor activity in the cat. AB - The hypothesis that the fluctuations in carotid chemoreceptor discharge represent more than a simple proportional response to respiratory oscillations of Pa, CO2 has been examined. Simultaneous recordings of the activity in few- or multi-fibre chemoreceptor preparations of the cut carotid sinus nerve and oscillations of carotid arterial pH have been made in four anaesthetized cats which were paralysed and artificially ventilated at constant frequency. Chemoreceptor activity was averaged over a minimum of twenty consecutive pH cycles and the amplitude of the fluctuations in discharge frequency determined. Using the mean Pa, CO2 obtained from blood-gas analysis and the slope of the relationship between log Pa, CO2 and pH obtained in each cat, the amplitude of the pH oscillations was converted to Pa, CO2 amplitude. This amplitude relative to the mean Pa, CO2 has been compared with the amplitude of the corresponding fluctuation in the chemoreceptor discharge frequency recorded from the carotid sinus nerve (e.s.n.d. amplitude) relative to its mean level. Whereas the Pa, CO2 amplitude was always less than 8% of the mean Pa, CO2, the c.s.n.d. amplitude ranged from 40 to 186% of the mean discharge frequency. C.s.n.d. amplitude was divided by the corresponding Pa, CO2 amplitude to give an index of the sensitivity of the chemoreceptors to Pa, CO2. This sensitivity has been compared with that determined from the mean discharge frequency produced in response to changes in mean Pa, CO2 comparable in magnitude to the Pa, CO2 amplitude. The former sensitivity was usually at least 3 times greater than the latter. Examination of the fluctuations in chemoreceptor discharge frequency in relation to the corresponding pH oscillations revealed that whereas the minimum discharge frequency coincided with the alkaline peak of the pH oscillation (trough of the Pa, CO2 oscillation), the maximum discharge frequency did not invariably coincide with the acid trough of the pH oscillation (peak of the Pa, CO2 oscillation). On 30% of occasions, the maximum discharge frequency was associated with the region of maximum rate of fall of pH (maximum rate of rise of Pa, CO2). It was concluded that fluctuations in the discharge of carotid chemoreceptors cannot be accounted for on the basis of a simple proportional relationship to Pa, CO2. They contain a large rate of change component. PMID- 3112370 TI - Responses of phrenic motoneurones of the cat to stimulation of medullary raphe nuclei. AB - Responses of phrenic motoneurones to stimulation of the three medullary raphe nuclei (raphe magnus (r. magnus), raphe obscurus (r. obscurus) and raphe pallidus (r. pallidus] were recorded in anaesthetized and decerebrated cats. Stimulation of r. magnus or r. obscurus depressed phrenic motoneurones. Stimulation at 100 Hz reduced action potential frequency within each inspiratory burst, without appreciable changes in inspiratory duration, or number of inspiratory bursts per unit time. The depression was proportional to the stimulus intensity (40-160 microA) and frequency (12-100 Hz) and lasted throughout the period of stimulation. Intracellular recording revealed concomitant depression of central respiratory drive potentials (c.r.d.p.s) and increased membrane input resistance during r. obscurus or r. magnus stimulation. In motoneurones which discharged action potentials during expiratory as well as inspiratory phases following intracellular chloride injection, stimulation of r. magnus or r. obscurus depressed cell firing during both phases. Both c.r.d.p.s and reversed inhibitory post-synaptic potentials (i.p.s.p.s) were depressed. These findings indicate that the depression is not related to post-synaptic inhibition of phrenic motoneurones. Stimulation (100 Hz) of r. pallidus produced discharges of action potentials in phrenic motoneurones. Stimulation lengthened the duration of each inspiratory discharge in proportion to stimulus intensity. Continuous firing occurred throughout the period of stimulation with maximal intensities. Intracellular recordings revealed sustained depolarization and reduction in membrane input resistance during the discharge. Responses were recorded extracellularly from medullary inspiratory neurones of the dorsal respiratory group (d.r.g.) and ventral respiratory group (v.r.g.) and from vagal axons which fired in phase with phrenic nerve activity. Responses to raphe stimulation were similar to those recorded from phrenic motoneurones. Evidence is presented that the responses are not related to stimulation of decussating bulbo-spinal axons from d.r.g. or v.r.g. neurones. It is suggested that medullary respiratory neurones receive inhibitory and excitatory synaptic inputs from medullary raphe neurones. Hypercapnia (5% CO2 in O2) or hypoxia (15% O2 in N2) reduced markedly the inhibition produced during stimulation of r. obscurus or r. magnus, and restored expiratory-linked silent periods during stimulation of r. pallidus. Activation of Hering-Breuer or baroreceptor reflexes did not alter responses to r. pallidus stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3112373 TI - Bacterial antibodies in patients undergoing treatment for denture stomatitis. PMID- 3112374 TI - Fetal blood flow measurements in severe rhesus isoimmunization. A case report. AB - Maternal isoimmunization can result in fetal anemia. Current management of isoimmunized pregnancies involves amniocentesis and spectrophotometry. Pulsed Doppler ultrasound can provide fetal blood flow determinations from the fetal umbilical vein. A pregnancy complicated by severe rhesus isoimmunization was studied with Doppler ultrasound. Increased fetal umbilical blood flow was associated with increased fetal hemolysis. Umbilical vein blood flow decreased after intrauterine transfusion. Doppler ultrasound assessment of fetal blood flow is a useful noninvasive adjunct in isoimmunized pregnancies. PMID- 3112372 TI - Effects of visual deprivation on the development of the monkey's lateral geniculate nucleus. AB - We have studied the physiological properties of cells in the deprived layers of the lateral geniculate nucleus (l.g.n.) in monkeys monocularly deprived from birth for up to 27 weeks, and compared them with results from the non-deprived layers in the same animals and in a series of normal animals. Despite the relative shrinkage of cell bodies in the deprived layers, units were easily isolated, were visually responsive and could readily be classified as linear (X) or non-linear (Y) by means of tests of spatial summation. The laminar distribution of cell types and the proportion of Y cells did not seem to be affected by deprivation. The patterns and latencies of discharge produced by contrast-reversing gratings did not differ grossly between deprived and non deprived cells. The peak firing frequencies for drifting gratings were also similar. The degree of surround antagonism (though very variable from cell to cell) seemed unaffected by deprivation. Most surprising of all, there was little or no deficit in the spatial resolution of the receptive fields of deprived cells. Recordings were always taken ipsilateral to the deprived eye, and neural 'acuity' tended to be sligtly lower in the deprived laminae than the non deprived. However, this nasal/temporal asymmetry in spatial resolution was not obviously more pronounced than in normal animals. Neural 'acuity' was not abnormally low in either contralateral or ipsilateral layers in the l.g.n. of an animal binocularly deprived from birth until a year of age. We have not examined chromatic properties or temporal characteristics adequately to say whether they are affected by deprivation. Paradoxically, although the post-natal maturation of visual acuity in normal monkeys seems to be mainly limited by peripheral factors, deprivation (which causes a profound defect of behavioural acuity) does not seem to interfere substantially with physiological development of the retina or the geniculate nucleus. PMID- 3112375 TI - Polyfunctional properties of hybridoma lupus anticoagulant antibodies. AB - Lupus anticoagulant antibodies are antiphospholipid antibodies which are characterized by their ability to prolong the clotting time in in vitro coagulation assays measuring the partial thromboplastin time (PTT). In our study, we have analyzed 11 hybridoma lupus anticoagulant antibodies and studied their reactivity with hexagonal and lamellar phospholipids, DNA, IgG, cytoskeletal components, and intact platelets. Our results demonstrate that hexagonal phase phospholipids but not lamellar phospholipids were able to neutralize the lupus anticoagulant activity of all 11 hybridoma antibodies. However, the lupus anticoagulant antibodies differed from one another in their reactivity with DNA, the Fc fragment of IgG, cytoskeletal proteins and platelets. Some of the lupus anticoagulant antibodies reacted with all of these structures, while others reacted with only some or none of the antigens tested. Isoelectric focusing gel analysis confirmed that this polyreactivity was due to a single antibody. Direct binding of lupus anticoagulant antibodies to intact platelets was shown to correlate with the DNA binding activity of the antibodies. Lupus anticoagulant antibodies were also capable of inducing a morphological shape change in platelets. Our data suggest that hybridoma lupus anticoagulant antibodies may react as lupus anticoagulant antibodies only, anti-DNA antibodies, rheumatoid factors, anticytoskeletal antibodies, and antiplatelet antibodies. The degree of overlap in these subgroups and the epitopes responsible for these multiple reactivities remain to be determined. PMID- 3112376 TI - Antiphospholipid antibodies: an elderly statesman Dons new garments. AB - Recent findings have renewed interest in antiphospholipid antibodies. The association of lupus anticoagulant with thrombosis, fetal loss, thrombocytopenia and possibly a Coombs' positive test is among these findings. A method to detect anticardiolipin antibodies and the association of these antibodies with the same clinical disorders as the lupus anticoagulant suggest a relationship between these 2 antibodies. PMID- 3112377 TI - Interleukin 2, T cell receptor and sex hormone studies in autoimmune mice. AB - Systemic lupus erythematosus (SLE) is a disease of immune dysregulation in which B cell hyperactivity and T cell deficiency are important characteristics. Sex factors also play a major role in the pathogenesis based on the physiologic effects of estrogen in promoting immunologic hyperactivity. Our findings suggest that a posttranscriptional mechanism is responsible for the functional interleukin 2 (IL-2) defect since transcription of the IL-2 message occurs after mitogenic stimulation. The proliferating cell in the MRL/lpr mouse model of lupus may be an immature T cell. The T cell receptor in these mice has a lower molecular weight than normal. This aberrant T cell receptor might be explained by a defect in glycosylation. The administration of estrogen to pregnant mice late in gestation results in offspring with a permanently altered immune system. These mice develop features of autoimmunity similar to those that occur spontaneously in genetically susceptible autoimmune mice. This phenomenon may have etiopathological significance for familial SLE. PMID- 3112378 TI - Dissection of the antigen presenting function of tissue cells induced to express HLA-DR by gamma interferon. AB - At sites of inflammation, cells that normally do not express class II products (la antigens) encoded by genes of the major histocompatibility complex such as fibroblasts and endothelial cells have been found to become Ia antigen positive, presumably as a result of the action of the T lymphocyte derived lymphokine gamma interferon (IFN-gamma). These cells may contribute to ongoing immunologically mediated inflammation by functioning as antigen presenting cells (APC). To test this hypothesis, fibroblasts and umbilical vein endothelial cells were treated with IFN-gamma to induce the expression of HLA-DR antigens. Both fibroblasts and endothelial cells became comparably HLA-DR positive in response to IFN-gamma. Despite this, endothelial cells but not fibroblasts became effective APC for resting T cells. HLA-DR positive fibroblasts could present antigen effectively to resting T cells; however, the HLA-DR negative endothelial cells were also present. These results indicate that expression of Ia is necessary but not sufficient for a cell to present antigen. The data also suggest that at inflammatory sites a number of cells may function in concert to promote antigen recognition by T lymphocytes. PMID- 3112379 TI - Managing drug addiction in general practice--the reality behind the guidelines: discussion paper. PMID- 3112380 TI - Two neutropenic patients with multiple resistant Pseudomonas aeruginosa septicaemia treated with ciprofloxacin. PMID- 3112381 TI - Spinal cord compression in Paget's disease of bone treated medically. PMID- 3112383 TI - Sheltered housing in primary geriatric health care in Hong Kong. PMID- 3112382 TI - Multiple injuries due to sting rays. PMID- 3112384 TI - Darkroom diseases and how to combat them. PMID- 3112385 TI - Reliability of road accident statistics. PMID- 3112386 TI - Radiological sciences in the pediatric radiology department. PMID- 3112387 TI - The Soviet Medical Centre for Diseases of Women and Children. PMID- 3112388 TI - AIDS--an international perspective. PMID- 3112389 TI - Schistosomiasis control in the southern province of Saudi Arabia. PMID- 3112390 TI - Diet and development in schoolchildren. PMID- 3112391 TI - Children's opinions and attitudes about smoking. PMID- 3112392 TI - Infant immunisation: do we need a media campaign? PMID- 3112393 TI - Infant protein energy malnutrition in Nigeria. PMID- 3112394 TI - Occupational allergy to laboratory animals. PMID- 3112395 TI - The effect of lateral and dorsal recumbency on cardiopulmonary function in the anaesthetised horse. AB - The effect of lateral and dorsal recumbency on cardiopulmonary function in six anaesthetised horses were compared. Cardiac output/kg, stroke volume/kg, alveolar ventilation, venous admixture, pulmonary shunt and blood-gas values were determined. From lateral to dorsal recumbency cardiac output/kg decreased non significantly. A significant increase in pulmonary shunt occurred. A positive correlation between body mass and pulmonary shunt in dorsal recumbency was found. Alveolar ventilation increased significantly in dorsal recumbency when breathing air compared to oxygen. PMID- 3112396 TI - Some aspects of superovulation and fertilisation of Dorper sheep. AB - Response of Dorper sheep to treatment with FSH and PMSG and fertilisation after natural service, natural service following application of PGF2 alpha-containing gel on the posterior os cervix and surgical insemination with fresh semen were evaluated. FSH gave a significantly (P greater than 0.05) better response than PMSG. No significant differences between the different methods of fertilisation were observed. PMID- 3112397 TI - Methotrexate analogues. 30. Dihydrofolate reductase inhibition and in vitro tumor cell growth inhibition by N epsilon-(haloacetyl)-L-lysine and N delta (haloacetyl)-L-ornithine analogues and an acivicin analogue of methotrexate. AB - Analogues of methotrexate (MTX) with strong alkylating activity were prepared by replacing the L-glutamate side chain with N omega-haloacetyl derivatives of L lysine and L-ornithine. Haloacetylation was accomplished in 30-40% yield by reaction of the preformed L-lysine and L-ornithine analogues of MTX with p nitrophenyl bromoacetate or chloroacetate in aqueous sodium bicarbonate at room temperature. All four haloacetamides were potent inhibitors in spectrophotometric assays measuring noncovalent binding to purified dihydrofolate reductase (DHFR) from L1210 cells. In experiments designed to measure time-dependent inactivation of DHFR from L1210 cells and Candida albicans, the N epsilon-(bromoacetyl)-L lysine and N delta-(bromoacetyl)-L-ornithine analogues gave results consistent with covalent binding, whereas N epsilon- and N delta-chloroacetyl analogues did not. The N delta-(bromoacetyl)-L-ornithine analogue appeared to be the more reactive one toward both enzymes. Amino acid analysis of acid hydrolysates of the L1210 enzyme following incubation with the bromoacetamides failed to demonstrate the presence of a carboxymethylated residue, suggesting that alkylation had perhaps formed an acid-labile bond. In growth inhibition assays with L1210 cultured murine leukemia cells, the four haloacetamides were all more potent than their nonacylated precursors but less potent than MTX. The greater than 40,000 fold MTX-resistant mutant cell line L1210/R81 was only partly cross-resistant to the haloacetamides. An analogue of MTX with acivicin replacing glutamate was a potent inhibitor of DHFR from chicken liver and L1210 cells but was 200 times less potent than MTX against L1210 cells in culture. PMID- 3112398 TI - [1-Desamino, 7-lysine, 8-arginine]vasotocin: attachment of reporter groups and affinity ligands through the lysine side chain. AB - The chemically reactive groups of [8-arginine]vasotocin (AVT) are the alpha-amino group in position 1, the phenolic hydroxyl group of the tyrosyl residue in position 2, and the side-chain functional group of the basic amino acid residue in position 8. Acylation or alkylation of any of these chemically reactive groups yields hormone analogues with sharply diminished biological activities in most assay systems. Since none of the chemically reactive groups in the native AVT (or other neurohypophyseal hormone) sequences is a suitable chemical port for acylation with affinity ligands and reporter groups, we have undertaken the rational design of AVT analogues in which a residue capable of being acylated has been incorporated into points of the AVT structure where structural modifications are expected to have as little effect as possible on biological activity. Empirical structure-activity relationships among neurohypophyseal hormone analogues as well as conformational models in solution and in the crystalline state suggest that positions 4 and 7 are likely points for the introduction of acylation ports. We have previously synthesized an analogue of [1-desamino]AVT (dAVT) with a lysyl residue in position 4 ([4-lysine]dAVT) and demonstrated that acylation of the side chain of this residue yields useful reporter and photoaffinity analogues. We now report the synthesis of the corresponding analogue with a lysyl residue in position 7 ([7-lysine]dAVT), which also yields potent acyl derivatives suitable for affinity ligands and photoaffinity ligands. PMID- 3112399 TI - Hydrophobicity-hydrophilicity of staphylococci. AB - The hydrophobicity-hydrophilicity of various strains of Staphylococcus has been studied by a technique involving partitioning of the cells between aqueous and hydrocarbon phases. S. aureus was typically hydrophobic, and to a greater degree in stationary- than in exponential-phase cultures. Mutants that lacked teichoic acid, protein A or coagulase production were hydrophobic, indicating that none of these factors was responsible for hydrophobicity. The presence of a capsule rendered strains hydrophilic. Thus, determination of hydrophobicity may be a useful additional test for capsulation. However, a non-capsulate S. aureus strain was hydrophilic. Trypsin treatment converted strains from hydrophobic to hydrophilic. Isolated bacterial cell wall preparation, either crude or purified, and peptidoglycan were hydrophilic. These results indicate that the determinant of hydrophobicity is a protein or protein-associated molecule localised at the cell surface of the organism, i.e., a component of either the cell wall, cell membrane, or both. Twenty-five strains of twelve coagulase-negative species were examined and most (18) were hydrophobic, again indicating that protein A is not a major determinant of hydrophobicity in these staphylococci. Four of seven hydrophilic strains were capsulate; three strains of S. sciuri were hydrophilic but non-capsulate. PMID- 3112400 TI - Interleukin 1 and interleukin 2 production in the acquired immune deficiency syndrome (AIDS) and AIDS-related complex. AB - Interleukin 1 (IL-1) production by freshly isolated and lipopolysaccharide (LPS) stimulated adherent monocytes-macrophages and IL-2 production by unstimulated and phytohemagglutinin (PHA)-activated T cells were examined in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC). Spontaneous IL-1 production was significantly increased in patients with ARC, whereas IL-1 production by LPS-activated monocytes-macrophages was significantly decreased in patients with AIDS. Spontaneous IL-2 production by unstimulated T cells was significantly decreased in AIDS and IL-2 produced by PHA-activated T cells was significantly decreased in AIDS and ARC. This study shows abnormality of both monocyte and T-cell functions in AIDS and ARC. These abnormalities appear to play a role in the immunopathogenesis of AIDS. PMID- 3112401 TI - Selective reduction of the OKT 4 positive 4B4 positive subset during HTLV III infection in humans. AB - Combinations of monoclonal antibodies defining the OKT 4 positive lymphocyte subset in the peripheral blood of intravenous drug abusers suggest that the 4B4 positive helper inducer population is greatly reduced in subjects infected with HTLV III. No differences were seen instead using different antibodies directed against various epitopes of the T4 molecule. These results suggest that the multiple marker assay could be very useful to define immunological status during HTLV III infection in humans. PMID- 3112402 TI - Surface marker studies on activated peripheral blood lymphocytes in idiopathic dilated cardiomyopathy. AB - Expression of interleukin 2 (IL-2) receptor on peripheral blood lymphocytes after stimulation with concanavalin A (Con A) or anti-T3 monoclonal antibody was analyzed in patients with dilated cardiomyopathy (DCM) in order to clarify the abnormalities of lymphocyte activation mechanism in DCM. The expression of IL-2 receptor after the stimulation with either Con A or anti-T3 monoclonal antibody was found to be reduced in the patients with DCM when the results were compared with those of controls. A significant correlation was noticed between the expression of IL-2 receptor after Con A stimulation and T4+/T8+ cell ratio, and between the expression of IL-2 receptor after anti-T3 monoclonal antibody stimulation and the left ventricular end-diastolic pressure (LVEDP). The results suggest that there are abnormalities of lymphocyte activation in DCM and that the alteration may be associated with the cause or clinical conditions of DCM. PMID- 3112403 TI - Prognostic implications of circulating immune complexes and Pseudomonas aeruginosa-specific antibodies in cystic fibrosis. AB - We re-examined the role of circulating immune complexes (CIC) in cystic fibrosis, by their serial measurement in 16 patients who had advanced lung disease and persistent specific antibodies to Pseudomonas aeruginosa in their serum. CIC were detected by 125I C1q-BA (IgG + IgM-IC) and Raji RIA (IgG-IC), and IgA-IC by a modification of the Raji RIA method. Serum precipitins to Ps. aeruginosa were detected by crossed-immunoelectrophoresis (XIE) and antibodies to alkaline protease (AP), elastase (EL) and exotoxin-A (EA) of Ps. aeruginosa were detected by ELISA technique. CIC were positive in greater than 50% of the samples in 8 patients (group A) and in less than 25% in the other 8 (group B); follow-up averaged 22 mo in group A and 26 mo in group B. The numbers of precipitins to Pseudomonas were equally high, and levels of antibodies to AP, EL, and EA of Ps. aeruginosa were similarly positive, in the 2 groups. In group A the CIC were mostly IgG-IC by Raji RIA (76%) and IgA-IC, whereas in group B C1q-binding IC (79%) and IgA-IC were more prevalent than IgG-IC by Raji RIA. Four group A children died during follow-up, together with one group B child in whom the CIC level had suddenly risen precipitously. We postulate that a high level of CIC in association with persistent specific-antibody response to Ps. aeruginosa heralds a poor prognosis in cystic fibrosis. PMID- 3112404 TI - The capacity of blood lymphoid cells to produce alpha- and gamma-interferon is decreased during alpha-interferon therapy. AB - The influence of alpha-interferon (alpha-IFN) therapy on the capacity of blood lymphoid cells to produce alpha- and gamma-interferon (IFN) was studied in 21 patients with gynecological tumors, i.e., ovarian carcinoma (14 patients) or condylomata accuminata (7 patients). The mean capacity of the lymphoid cells to produce alpha-IFN in response to Sendai virus was increased, although not statistically significant, as compared to an age- and sex-matched control group, whereas the mean capacity of the patients' blood lymphoid cells to produce gamma IFN in response to PHA or PWM was slightly decreased as compared to the control group. One day after the first injection of alpha-IFN there was a statistically significant decrease in the capacity of blood lymphoid cells to produce alpha-IFN and this decrease remained after 3 months of IFN therapy in most patients investigated. One week after initiation of alpha-IFN therapy there was a statistically significant decrease in the capacity of the cells to produce gamma IFN in response to PHA or PWM and in most patients studied this decrease remained after 3 months of treatment. We conclude that the capacity of blood lymphoid cells to produce IFN is suppressed during exogenous alpha-IFN therapy. PMID- 3112405 TI - Recurrent meningococcal meningitis associated with deficiencies of C8 and anti meningococcal antibody. AB - A patient with fatal recurrent meningococcal meningitis is described. Detailed complement and immunological investigation revealed a combined deficiency of C8 and anti-meningococcal antibody. An inability to make anti-meningococcal antibody in C8 deficient patients has not been previously reported. PMID- 3112406 TI - Determination of ovulation and pregnancy in the marmoset (Callithrix jacchus) by monitoring of urinary hydroxypregnanolone excretion. AB - In Callithrix jacchus the urinary excretion of hydroxypregnanolone (5 alpha pregnane-3 alpha, 7 alpha-diol-20-one) shows a luteal rise during the ovulatory cycle. This progesterone metabolite can therefore be used as an indication of ovulation, implantation, and subsequently for the persistence of the pregnancy. The excretion can be monitored by high performance thin-layer chromatography (HPTLC) and postchromatographic derivatization after enzymatic hydrolysis of the conjugate. Profiles of urinary hydroxypregnanolone levels are presented and correlated with luteinizing hormone excretion. The method is noninvasive and therefore suited for long-term studies in these monkeys. PMID- 3112407 TI - Fluorescent measurements of intracellular free calcium in isolated toad urinary bladder epithelial cells. AB - Sodium-calcium exchange has been suggested to play a pivotal role in the regulation of cytosolic free calcium (Caf) by epithelial cells. Using isolated epithelial cells from the toad urinary bladder, Caf has been measured using the intracellular Ca-sensitive fluorescent dyes Fura 2 and Quin 2. Dye loading did not alter cell viability as assessed by measurements of ATP and ADP content or cell oxygen consumption. When basal Caf was examined over a wide range of cell dye content (from 0.04 to 180 nmol dye/mg protein) an inverse relationship was observed. At low dye content, Caf was 300-380 nM and, as dye content was increased, Caf progressively fell to 60 nM. Using low dye content cells, in which minimal alteration in Ca steady state would be expected, the role for plasma membrane Na-Ca exchange was examined using either medium sodium substitution or ouabain. While medium sodium substitution increased Caf, prolonged treatment with ouabain had no effect on Caf despite a clear increase in cell sodium content. The lack of effect of ouabain suggests that Na-Ca exchange-mediated Ca efflux plays a minimal role in the regulation of basal Caf. However, exchange-mediated Ca efflux may play a role in Caf regulation when cytosolic calcium is elevated. PMID- 3112408 TI - Prostaglandin E2-stimulated glandular ion and water secretion in isolated frog skin (Rana esculenta). AB - Prostaglandins are known to stimulate the active sodium absorption in frog skin. In this paper it is shown that prostaglandin E2 (PGE2) stimulates an active secretion of Cl-, Na+, and K+ from the skin glands in Rana esculenta. The active Cl secretion is enhanced more than the Na and K secretion. Therefore, in skins where the Na absorption is inhibited by amiloride, the addition of PGE2 results in an increase in the short-circuit current (SCC). The PGE2-stimulated Cl secretion could be inhibited by the presence of ouabain or furosemide in the basolateral solution or diphenylamine-2-carboxylate in the apical solution. The PGE2-stimulated Cl secretion was enhanced by the phosphodiesterase inhibitor, theophylline, indicating that the effect of PGE2 was caused by an increase in the intracellular cAMP level in the gland cells. The calcium ionophore A23187, which increases the PGE2 synthesis in frog skin, stimulated the glandular Cl secretion. This secretion could be blocked by the prostaglandin synthesis inhibitor indomethacin, indicating that A23187 acts by increasing the prostaglandin synthesis and not by a direct action of Ca2+ ions per se. The net water flow (Jw) and the Cl secretion were measured simultaneously under the conditions outlined above. The stimulation, inhibition, and the time-course of the outward-directed Jw were similar to the change observed for the Cl secretion. These results show that PGE2 stimulates a glandular secretion of Cl and water in frog skin, probably by increasing the cAMP level in the gland cells. PMID- 3112409 TI - Mechanisms of frameshift mutagenesis by aflatoxin B1-2,3-dichloride. AB - In order to characterize frameshift mutagenesis by aflatoxin B1-2,3-dichloride (AFB1Cl2), we have introduced a +1 (BK8) or a -1 (HS8) frameshift within the lacZ alpha gene segment contained in the phage M13mp8 to obtain lacZ alpha- derivatives. BK8 or HS8 replicative form DNA was modified with AFB1Cl2 in vitro, transfected into appropriate Escherichia coli hosts and lacZ alpha+ revertants scored and defined by DNA sequencing. The -1 frameshift (BK8) results suggest the following. (1) The E. coli recA gene is not absolutely required for AFB1Cl2 induced frameshift mutagenesis; however, in recA+ cells, ultraviolet light (SOS) induction enhances AFB1Cl2 mutagenesis, but such ultraviolet induction is not required. The plasmid pGW270 (mucAB+) significantly enhances the AFB1Cl2-induced frameshift mutagenesis. The uvrABC+ excision system plays a major role in the repair of AFB1Cl2-induced damage. (2) Sequence analysis reveals that AFB1Cl2 induces two classes of -1 frameshift mutations: the simple class in which the frameshift is due to the loss of one base-pair, and the complex class in which the loss of a base-pair is coupled to a vicinal base substitution. Both types of mutations occur predominantly at G.C runs, which are hotspots for AFB1Cl2 damage. The complex mutations appear to be concerted events targeted by a single AFB1Cl2 adduct. The frequency of these complex mutations is significantly enhanced by mucAB activity. In this system, recA activity is required for generation of significant levels of complex mutations. An analysis of the +1 frameshifts (HS8) reveals that AFB1Cl2 induces +1 frameshifts with an efficiency comparable to that for -1 frameshifts. Most +1 frameshifts occur by the addition of a base, and a third of the additions are complex mutations because they are accompanied by at least one base substitution. All simple additions occur at G.C runs; however, in a striking contrast to spontaneous insertions, a majority of the induced events introduce an A.T pair at these sites. Our data suggest a model for the generation of base substitution as well as simple and complex frameshift mutations induced by AFB1Cl2. To the extent determined, the frameshift specificity of aflatoxin B1 activated by metabolic enzymes is similar to that of AFB1Cl2. PMID- 3112410 TI - The innermost chorionic layer of Drosophila. I. The role of chorin octamers in the formation of a family of interdigitating crystalline plates. AB - The innermost chorionic layer (ICL) within egg shells of Drosophila melanogaster is composed of thin, abutting three-dimensional crystalline plates which form a closed, membrane-like sheath. Collectively, the crystals within the sheath appear to form a family of related three-dimensional crystals in space group C222; however, specimens prepared for electron microscopy are actually two-dimensional crystals in c222. The projected structures of the negatively stained crystals have been studied by minimal dose electron microscopy employing image reconstruction methods. Thin sections indicate that unit cells within the ICL are composed of paired layers; top and bottom layers are related by centrally located 2-fold axes, aligned parallel to the surface of the ICL. The most probable structural unit of the crystals is a tetramer of chorin dimers with a point group symmetry of 222, which is denoted a chorin octamer. Projection maps were computed from average transforms of two-dimensional crystals for delta (the primitive unit cell angle) equal to 84 degrees, 90 degrees and 97 degrees (+/- 1.5 degrees). The maps indicate that the molecular transitions responsible for the observed family of crystals involve concerted intramolecular rearrangements about molecular 2 fold axes. The significance in vivo of the family of crystals within the ICL is not known; however, structural considerations suggest that the observed polymorphism may reflect one facet of an intrinsic bonding flexibility of the ICL octamer that may play a role in the formation of interplate junctions and the assembly of a continuous closed sheath. The ICL may therefore serve as a structural bridge between the vitelline membrane-wax layer and the endochondrial floor, allowing the larva to shed the inner egg shell layers during hatching. PMID- 3112411 TI - The innermost chorionic layer of Drosophila. II. Three-dimensional structure determination of the 90 degrees crystal form by electron microscopy. AB - The innermost chorionic layer (ICL) within egg shells of Drosophila is composed of a family of related, thin three-dimensional crystals that form a continuous sheath encapsulating the egg shell lumen. Junctions formed by interdigitating lattices play a central role in the construction of this macroscopic assembly. The three-dimensional structure of a two-dimensional crystal isolated from the ICL, with a primitive lattice angle delta of 90 degrees, has been determined from a complete tilt series of a negatively contrasted specimen at a resolution of 25 A. Inspection of the three-dimensional transform after data merging revealed that the space group is c222 and this symmetry was employed to generate a three dimensional structure. The basic structural unit of the ICL is an octamer, described formally as a tetramer of dimers with point group symmetry 222. There are two classes of dimer in the octamer designated alpha and beta. The chorin octamer is composed of two classes of bent dimers, which make intramolecular contacts at the top and bottom of the molecule. The alpha-dimers are curved outwards away from the crystallographic 2-fold axis, while the beta-dimers are curved towards the molecular center. In addition, lattice contacts are formed primarily by beta-chorin dimers at both the top and bottom surfaces of the unit cell. The molecular weight of a chorin octamer determined from the analysis is about 6 X 10(5). The conformation of the chorin octamer determined here suggests that permutations of a basic molecular mechanism may be adequate to explain both the observed lattice polymorphisms of the ICL and the formation of interplate junctions necessary for the assembly of the macroscopic sheath. PMID- 3112412 TI - Specificity of the attenuation response of the threonine operon of Escherichia coli is determined by the threonine and isoleucine codons in the leader transcript. AB - Expression of the threonine (thr) operon enzymes of Escherichia coli is regulated by an attenuation mechanism. The regulatory portion of the operon contains a region coding for a leader peptide that contains consecutive threonine and isoleucine codons. It is thought that translation of the leader peptide controls the frequency of transcription termination at the attenuator site. Using oligonucleotide-directed site-specific mutagenesis we have altered the putative control codons of the leader peptide coding region. In two of the mutants the threonine and isoleucine codons were changed to produce peptides containing histidine and tyrosine codons. Both mutants showed loss of regulation by threonine and isoleucine. A hisT mutation, which leads to an undermodification of tRNA(His), increased thr operon expression in the mutants threefold but did not affect expression of the wild-type thr operon. Two other mutants were constructed that contained two histidine codons early in the leader peptide. Expression in both of these mutants was unaltered by the presence of the hisT allele or by the addition of threonine and isoleucine to the growth medium. In addition, a wild type strain containing a temperature-sensitive threonyl-tRNA synthetase mutation showed increased thr operon expression at the non-permissive temperature, whereas none of the mutants showed any change. Taken together these data indicate that the specificity of the attenuation response is effected by specific control codons within the thr leader peptide coding region. We have also directly demonstrated thr leader peptide synthesis in vitro using a plasmid encoding the wild-type thr leader region to direct the synthesis of a peptide of the appropriate molecular weight when labeled with [3H]threonine but not with [3H]histidine or [3H]tyrosine. Conversely, when extracts were incubated with templates containing the mutated DNAs, peptides were labeled that showed patterns consistent with the expected amino acid compositions. These data indicate that the thr leader RNA is translated into the predicted leader peptide. PMID- 3112413 TI - Identical satellite DNA sequences in sibling species of Drosophila. AB - The evolution of simple satellite DNAs was examined by DNA-DNA hybridization of ten Drosophila melanogaster satellite sequences to DNAs of the sibling species, Drosophila simulans and Drosophila erecta. Seven of these repeat types are present in tandem arrays in D. simulans and each of the ten sequences is repeated in D. erecta. In thermal melts, six of the seven satellite sequences in D. simulans and seven of the ten sequences in D. erecta melted within 1 deg.C of the corresponding values in D. melanogaster. The remaining sequences melted within 3 deg.C of the homologous hybrids. Therefore, there is little or no alteration in those satellite sequences held in common, despite a period of about ten million years since the divergence of D. melanogaster and D. simulans from a common ancestor. Simple satellite sequences appear to be more highly conserved than coding regions of the genome, on a per nucleotide basis. Since multiple copies of three satellite sequences could not be detected in D. simulans yet are present in D. erecta, a species more distantly related to D. melanogaster than is D. simulans, these sequences show discontinuities in evolution. There were major quantitative variations between species, showing that satellite DNAs are prone to massive amplification or diminution events over timespans as short as those separating sibling species. In D. melanogaster, these sequences amount to 21% of the genome but only 5% in D. simulans and 0.4% in D. erecta. There was a general trend of lower abundance with evolutionary distance for most satellites, suggesting that the amounts of different satellite sequences do not vary independently during evolution. PMID- 3112414 TI - Adjacent satellite DNA segments in Drosophila structure of junctions. AB - The structure of eight satellite DNA molecules containing a junction between tandem arrays of different repeated sequences is described. In one class of junctions there was an abrupt switch with the juxtaposition of two satellite arrays. These arrays were closely related and the periodicity of repeats was maintained in phase across the junction. These arrays usually showed extreme homogeneity in their repeating sequences. A second class of junctions was more complex, and in two cases may have arisen by the insertion of a mobile element into a satellite array. A novel mechanism of satellite formation is proposed to explain the precision of junctions and sequence similarities of neighboring satellite arrays. Homogeneous satellite arrays would be generated enzymatically by synthesis of a repeat using the preceding repeat as template. Occasional errors in copying of the template, either single base changes or misreading the length of the repeat unit, would lead to abrupt switches in the repeating sequence. PMID- 3112415 TI - Technique of postoperative pelvic radiation in the management of rectal and rectosigmoid carcinoma. AB - Improper postoperative pelvic radiation of 5,000 rad in five weeks results in poor patient tolerance, unacceptable complications, and increased local recurrence. Preoperative or postoperative low-dose pelvic radiation results in better tolerance; however, in patients with resectable adenocarcinoma of the rectum and rectosigmoid, low-dose radiation improves neither the local failure rate nor the survival rate compared with treatment by surgery alone. The authors' technique was to deliver 5,000 rad in six weeks only to the pelvic tissues at risk for recurrence following surgery. PMID- 3112416 TI - The first simultaneous intraoperative hyperthermia and radiotherapy procedure: dog experiment and technique. AB - The Department of Radiation Therapy of Howard University Hospital was the first to revive (1976) the use of intraoperative radiotherapy, or direct view irradiation, using electron beam (IORTe(-)) in the United States. Since that time, this pioneering effort has gained both national and international acceptance. Now, many leading centers employ this investigational treatment modality. Recently, a new mode of cancer therapy has been gaining acceptance, namely hyperthermia (the treatment of cancer by heat). Hyperthermia has been shown, both experimentally and clinically, to improve the rate of local control (thermal enchancement ratio [TER]) when combined with radiation therapy in the treatment of cancer. Maximal TER has been observed with simultaneous or immediate application of radiation and hyperthermia for both tumor and normal tissues. Therefore, to achieve maximum therapeutic gain, selective, intraoperative, simultaneous heating and irradiation of the tumor with mechanical retraction of the normal and sensitive structures from the treatment field seems a promising alternative.There have been no published reports, to the authors' knowledge, on the combination of simultaneous IORTe(-) with intraoperative hyperthermia (IOHT). To employ this combination in human subjects, several questions must be answered first using animal models, including the technical and practical feasibility, the toxicity and morbidity, as well as the pathologic changes that may arise. The technical aspects of the first animal case, using a mongrel dog, applying simultaneous IORTe(-) and IOHT are presented. PMID- 3112418 TI - Sister chromatid exchanges in laboratory cultured cells after repeated exposures to pulsed ultrasound. AB - In this in vitro study, suspensions of DON cells (lung diploid cell line from the Chinese hamster) were exposed to ultrasound regimes using pulse lengths similar to those used in ultrasonic Doppler measurements of fetal blood flow. The base level frequency of sister chromatid exchanges (SCE) was not significantly altered following exposure to a range of spatial peak temporal average intensities from 0.1 to 4.0 W/cm2. Repeating the exposure on three further occasions during the 20 generations following the initial insonation also had no effect. When DON cells were incubated in the presence of Mitomycin C (MCC), a positive dose-related increase in SCE frequency was observed, indicating the sensitivity of these cells to in vitro SCE induction. Coincidental exposure to ultrasound and Mitomycin C did not increase the SCE level above that obtained with MCC alone, and it was concluded that there was no evidence of a synergistic association. PMID- 3112417 TI - Permeability changes in hepatic mitochondria and altered glucose and urea metabolism in aroclor 1254-treated rats. AB - The influence of Aroclor 1254 (ARO) treatment or pair-feeding (PF) on gluconeogenesis and urea synthesis and on isolated hepatic mitochondria was studied in rats of different ages. ARO (300 mg/kg, po on 4 consecutive days) induced variable weight loss in young (153 +/- 10 g (initial wt), -10.9%), intermediate-age (195 +/- 10 g, -17.0%), and old (232 +/- 23 g, -4.9%) rats. Isolated mitochondria contained equal amounts of cytochromes aa3, b, c1 and c with exception that c1 and c were lower in the young ARO rats than in the PF controls. Mitochondria from ARO rats, which lost more weight than ad libitum-fed (AF) rats, showed suppression of ADP-stimulated H+ and oxygen uptake and succinate plus valinomycin maximal swelling in a potassium acetate and sucrose medium. Mitochondria from young ARO rats absorbed less incident light than mitochondria from PF or AF rats. Maximally swollen mitochondria from intermediate age ARO rats, contracted more rapidly with antimycin addition than those from PF or AF controls. These findings showed greater permeability of ARO mitochondria to impermeable and accumulated ions. In contrast, mitochondria from ARO rats without significant weight loss showed activation of ADP-stimulated H+ and oxygen uptake and maximal swelling in comparison to mitochondria from AF and PF rats, but contracted like these controls after the antimycin addition. Urea synthesis in ARO rats, which lost 9.9% of initial body wt (173 +/- 6 g) and experienced a nitrogen deficit (Ebner et al., 1986), was significantly increased 12 min postinjection of NH4 acetate, and was greater than the urea level in AF rats at this time point. In comparison, gluconeogenesis was significantly increased in AF rats 12 min postinjection of NH4 acetate and was greater than in ARO rats at this time point. These differences were also observed when the data were expressed as the rate of glucose or urea appearance in peripheral blood per 100 g body wt. In PF rats, blood glucose and urea concentrations were intermediate to and indistinguishable from the ARO and AF groups. These data demonstrate that hepatic mitochondria from ARO rats that experienced a significant loss of body weight were suppressed and more permeable to ions than AF and PF controls. These mitochondrial properties may have predisposed the ARO rats toward urea formation rather than glucose synthesis and nitrogen retention. PMID- 3112419 TI - Systemic availability of penicillin V from six oral preparations in dogs. PMID- 3112420 TI - Immediate medical consequences of nuclear accidents. Lessons from Chernobyl. AB - The immediate medical response to the nuclear accident at the Chernobyl nuclear power station involved containment of the radioactivity and evacuation of the nearby population. The next step consisted of assessment of the radiation dose received by individuals, based on biological dosimetry, and treatment of those exposed. Medical care involved treatment of skin burns; measures to support bone marrow failure, gastrointestinal tract injury, and other organ damage (ie, infection prophylaxis and transfusions) for those with lower radiation dose exposure; and bone marrow transplantation for those exposed to a high dose of radiation. At Chernobyl, two victims died immediately and 29 died of radiation or thermal injuries in the next three months. The remaining victims of the accident are currently well. A nuclear accident anywhere is a nuclear accident everywhere. Prevention and cooperation in response to these accidents are essential goals. PMID- 3112421 TI - New hope for neurofibromatosis? The mast cell connection. PMID- 3112422 TI - Adrenal-to-brain transplants continue as neurologists test two new drugs. PMID- 3112423 TI - Fuel preferences in the septic patient: glucose or lipid? PMID- 3112424 TI - The second decade: a new beginning. PMID- 3112425 TI - Hormonal and metabolic responses to glucose infusion in sepsis studied by the hyperglycemic glucose clamp technique. AB - Although nutritional support is vital to treatment of severe sepsis, the septic patient does not respond normally to glucose infusion. We have used the hyperglycemic glucose clamp technique to investigate the initial hormonal and metabolic responses of the septic patient to glucose under controlled conditions. The plasma glucose concentration was raised to and maintained at 12 mmol/liter for 2 hr in 12 septic patients and 11 normal controls. Glucose utilization, assessed from the amount infused, was significantly depressed in the patients, despite similar plasma insulin concentrations in the two groups. Forearm glucose uptake was similarly impaired. Despite very similar plasma free fatty acid concentrations in the two groups, which were suppressed equally by the glucose infusion, whole-body fat oxidation was elevated in the patients compared with the controls, and suppressed to a lesser extent in response to glucose. Glycerol and ketone body concentrations were elevated in the patients in keeping with a picture of accelerated release, clearance, and oxidation of fatty acids. Plasma cortisol, epinephrine, and norepinephrine concentrations were elevated in the septic patients in a severity-related manner, but not to high levels compared with experimental work. Norepinephrine showed no response to the glucose infusion in either group. Plasma glucagon concentrations were not significantly elevated in the septic patients. We conclude that the hyperglycemic glucose clamp provides a useful model for studying glucose intolerance in sepsis. Impaired glucose utilization in septic patients is associated with increased fat oxidation, although the hormonal basis for these changes is still unclear. PMID- 3112426 TI - Hypomagnesemia: a multifactorial complication of treatment of patients with severe burn trauma. AB - Hypomagnesemia is reportedly a common complication of care during the early period of recovery from major trauma. Aminoglycoside treatment, by provoking inappropriate renal magnesium wasting, may contribute to the frequency of hypomagnesemia. We examined the magnesium (Mg) status of six severely burned adolescents during the early phase of recovery. Although provision of Mg met recommended levels, hypomagnesemia occurred in every patient. Two of five of our patients were hypomagnesemic during gentamycin treatment, and five of five during subsequent tobramycin therapy (including the three not affected by gentamycin). Additional episodes occurred in five patients in the absence of aminoglycosides. An interrelationship between Mg status and efficacy of potassium repletion is detailed for one patient. Hypomagnesemia during tobramycin treatment was associated with refractoriness to potassium repletion. Recurrence of hypokalemia during a subsequent diuresis-induced hypomagnesemia was prevented by Mg supplementation. The Mg requirement is increased during recovery from severe burns and appears to exceed that provided by commercially available enteral formulations. PMID- 3112427 TI - Studies on the toxicity and efficacy of a new amino acid solution in pediatric parenteral nutrition. AB - The optimum composition and concentration of crystalline amino acid solutions necessary for growth and brain maturation in critically ill infants requiring total parenteral nutrition (TPN) are unknown. Either an excess or a deficiency of amino acids could theoretically impair normal brain development in the neonate. The purpose of this study was to compare the toxicity and efficacy of two intravenous amino acid solutions, Neopham, modeled after the amino acid pattern found in human breast milk, and Aminosyn, a marketed product, designed for general usage. Sixteen infants and children requiring continuous intravenous nutrition for at least 7 days received the Neopham amino acid solution, and eight infants and children received the Aminosyn amino acid solution as part of a total parenteral nutrition regimen which included glucose, the fat emulsion Intralipid, as well as routine mineral and vitamin additives. There were no significant differences in mean gestational age, body weight, postnatal age, or mean daily nutrient intake between the patients receiving Aminosyn or Neopham. The daily nitrogen intake, excretion, and retention were similar in both groups. In addition, there were no statistically significant differences in either hematological or biochemical parameters between the two study groups. The plasma levels of three essential amino acids, isoleucine, methionine, and valine, rose significantly higher in the Aminosyn-treated patients. The plasma levels of all the essential amino acids increased in both study groups. PMID- 3112428 TI - Clinical efficacy and design changes of "fine bore" nasogastric feeding tubes: a seven-year experience involving 809 intubations in 403 patients. AB - We report here our clinical experiences of "fine bore" nasogastric feeding tubes. Data have been collated over a 7-year period (1978-1985). A total of 403 patients were intubated on 809 occasions. In the first retrospective study, the clinical use of 491 unweighted tubes was compared with that of fifty 3.5-g weighted tubes. No advantage was found in the use of the weighted tubes. In the second prospective controlled clinical trial, these results were confirmed. Forty-six patients were intubated on 76 occasions with an 85-cm open-ended, unweighted nasogastric feeding tube (Prima, Portex UK), and 57 patients were intubated on 79 occasions with a 91-cm 3.0-g weighted tube (Entriflex, Biosearch, Raritan, NJ). Mean duration of placement was similar in each case, and 62% of both types of tubes were inadvertently removed. Without exception, all the tubes remained in the stomach throughout. Disappointed with the similar and overall performance of both types of tubes, we initiated a design program which resulted in the development of two new nasogastric tubes, one weighted and one unweighted. The tubes were manufactured with polyurethane, rather than polyvinylchloride (PVC), which permitted an increase in diameter of the internal lumen which, in turn, was coated with water-activated lubricant to ease removal of the introducer wire. A specially modeled outflow port was incorporated into the tips of both tubes. The performance of the two new polyurethane nasogastric feeding tubes was assessed under controlled trial conditions; as a reference, a widely used PVC unweighted open-ended tube was used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112429 TI - Effect of amino acid solutions on total nutrient admixture stability. AB - The stability of total nutrient admixture (TNA) systems containing a soybean oil emulsion (Soyacal) has been reported with only one amino acid (AA) solution. This study was conducted to compare the physical stability of 10 TNA systems varied only by the AA solution used. All systems contained electrolytes, vitamins, trace elements, and heparin. The volume ratios of AA, dextrose 70% and lipid emulsion 20% were 1:1:1. Solutions were stored at 4 degrees C for 14 days and then held at ambient temperature for an additional 4 days. Each TNA was serially analyzed on days 0, 1, 3, 5, 7, 14, 15, 16, 17, and 18 for gross visual appearance, pH, osmolality, mean particle diameter, and particle size distribution. The AA solutions evaluated include: Travasol 8.5% and 10%; Aminosyn 8.5% and 10%, Aminosyn RF 5.2%; FreAmine III 8.5% and 10%; FreAmine HBC 6.9%; HepatAmine 8.0%; and NephrAmine 5.4%. The pH values of the Aminosyn solutions were lower than those of other products; however, the pH values of all TNA systems were greater than 5.7, which supported particle stability. The osmolality was not affected by the AA solutions. Based upon particle size distribution, 95% of all particles were less than 0.608 micron in diameter, with means ranging from 0.286 micron to 0.309 micron. The largest particle observed by light microscopy was 6.9 micron. These data indicate that TNA systems prepared with the 10 AA solutions and Soyacal 20% are physically stable. PMID- 3112431 TI - The growth of microorganisms in total parenteral nutrition admixtures. AB - Total nutrient admixtures (TNAs) containing glucose, amino acids, and lipid emulsion in one container and amino acid/dextrose solutions [conventional total parenteral nutrition (TPN) formulations] were studied in a controlled laboratory experiment for their ability to support the growth of microorganisms. Both TNA and conventional TPN formulations for peripheral and central venous administration with standard additives were inoculated with microorganisms to provide 10(1)-10(2) colony-forming units/ml (CFU/ml) of Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. The admixtures were stored at room temperature and samples for quantitative microbiology were taken at time 0, 6, 12, 24, 48, 72, and 96 hr. K. pneumoniae, E. coli, and P. aeruginosa were able to proliferate in central TNAs, but the growth of these organisms was retarded in conventional TPN solutions. In the peripheral formulations, K. pneumoniae and E. coli proliferated in both the TNA and conventional TPN systems, whereas P. aeruginosa grew well only in the peripheral TNA. S. epidermidis was not able to grow in any admixtures tested; however, C. albicans grew well in all admixtures, but growth was slower in the conventional central TPN. In conclusion, peripheral and central TNAs supported the growth of microorganisms significantly better than conventional TPN solutions. PMID- 3112430 TI - A comparison of intestinal adaptation to short-term intravenous versus intragastric diet in adult rats. AB - This study was designed to determine, on intestinal function, the comparative effects of a fat emulsion, a carbohydrate solution, and a mixture of lipids and carbohydrates given for 4 days to adult rats either intragastrically or intravenously. The rats were separated into three groups (n = 24 in each group). Each group was divided into two populations fed either intragastrically or intravenously. Each group received one of the following nutrients: a 20% Intralipid emulsion, a mixture (1:1, V/V) of Intralipid 20% and Vamine N containing 25% glucose (W/V), a solution of Vamine-glucose supplemented with fructose to reach a final concentration of 20% (W/V). Sham-operated rats that received laboratory chow orally were used as controls. The daily caloric intake was 0.21 to 0.22 kcal/g body weight. The studies on villus morphology and on brush border enzyme activities were performed on the proximal part of the jejunum. For all nutrients, intragastric infusion provoked an increase in the villus height. The lipids were the only nutrients to cause villus lengthening by the intravenous route. Intragastric or intravenous infusion of fat provoked a deficiency in intestinal disaccharidases; the presence of carbohydrates in the diet inhibited this effect slightly. Carbohydrates given alone, either intragastrically or intravenously, caused an elevation of lactase activity. Independent of diet composition, aminopeptidase activity was reduced after intravenous feeding. In conclusion, the disaccharidase activities are largely dependent on changes occurring in the nutrient composition given either intragastrically or intravenously, whereas amino-peptidase activity was related to the route of diet administration. PMID- 3112433 TI - Nutrition education in schools of nursing in the United States. Part 2: The status of nutrition education in schools of nursing. AB - To explore whether nurses in academic institutions are being adequately educated to care for patients' nutritional needs, we conducted a survey of National League for Nursing accredited baccalaureate programs in the United States and their associated graduate programs. Data indicate that nutrition content is an integral part of baccalaureate nursing programs. Less emphasis is reported on nutrition content at the graduate level. Recommendations include revision of the substantive nutritive content and increased clinical experience in nutrition in both undergraduate and graduate nursing education. PMID- 3112432 TI - Contamination rates of 3-in-1 total parenteral nutrition in a clinical setting. PMID- 3112434 TI - Reversal of severe serous atrophy of the bone marrow in anorexia nervosa. AB - The patient described in this case report had anorexia nervosa, which ultimately was fatal. She presented with complete serous atrophy of the bone marrow associated with pancytopenia. After 2 weeks of intensive nutritional support, her peripheral blood counts had returned to normal. At autopsy on day 24, the serous atrophy had resolved and the bone marrow was populated by normal numbers of hematopoietic precursors. This case is unique in demonstrating that starvation induced severe serous atrophy of the bone marrow is reversible with nutritional intervention. PMID- 3112435 TI - Total parenteral nutrition in pregnancy: conception to delivery. AB - The delivery of safe and nutritionally successful total parenteral nutrition (TPN), including intravenous lipid emulsion, to a pregnant woman with Crohn's disease and short bowel syndrome from conception to delivery is reported. Maternal nutritional status improved during the pregnancy. Fetal development was normal, and a healthy, full-term infant was delivered. The placenta was normal. Specific intravenous macronutrient and micronutrient requirements during pregnancy are not well defined. Our experience has resulted in the generation of additional recommendations to optimize the intravenous nutritional therapy of this high-risk population. PMID- 3112436 TI - Altered lipoxygenase metabolites and leukocyte involvement in an acute occlusion reperfusion model of canine myocardial infarction. AB - We compared amounts of lipoxygenase products with the extent of leukocyte infiltration in the ischemic myocardium with an occlusion-reperfusion model of open-chest dog. Changes in peripheral leukocyte count and leukocyte function estimated by neutrophil aggregation induced by calcium ionophore A23187 were also examined. The ischemic tissue (120 +/- 40 ng/g, mean +/- SEM) showed a marked increase in 12-hydroxyeicosatetraenoic acid (HETE) production compared with the normal tissue (13 +/- 1 ng/g, p less than 0.01). The production of 5-HETE in the ischemic tissue was also augmented as well. When we examined the correlation between production of either 12-HETE or 5-HETE and leukocyte infiltration in the ischemic tissue, the former was augmented markedly in proportion to the extent of the latter. Leukocyte count in peripheral circulation was gradually increased after reperfusion. Similarly, neutrophil aggregation was significantly augmented during reperfusion. These results indicate that production of lipoxygenase metabolites associated with leukocyte infiltration in the reperfused ischemic tissue was increased during the course of myocardial infarction, which was accompanied by activation of leukocyte in peripheral circulation. Further studies should be done to clarify the importance of lipoxygenase metabolites in the evolution of reperfusion-induced myocardial injury. PMID- 3112437 TI - [Effect of low flow anesthesia on respiratory metabolism; continuous measurement of VO2, VCO2 and RQ in surgical patients]. PMID- 3112438 TI - [Hypoxemia observed following emergency neurosurgery]. PMID- 3112439 TI - [Combination chemotherapy of UFT, etoposide and CDDP in advanced gastric cancer]. AB - Eleven patients with advanced unresectable gastric cancer were treated with a combination of UFT, etoposide and CDDP (FFP). FEP regimen was given every 4 weeks as follows: UFT 400 mg/m2 (p.o.) everyday, etoposide 50 mg/m2 (i.v.), and CDDP 30 mg/m2 (i.v.) on day 1, 8, and 15. The subjects were 3 males and 8 females with an average of 64 (ranging from 44 to 84 yrs). None had had prior chemotherapy. One patient was in performance status (P.S.) 1, 6 were in PS 2, and 4 were in PS 3. Partial responses (PR) were obtained in 5 out of 11 patients. The durations of the response were over 3 months in all patients with PR. No side effects were observed except for mild myelosuppression and nausea. In BALB/C mice with lymphoid leukemia L1210, the effects of each drug and the combination of the two or three drugs on the increase in life span (ILS) were studied. The combination of the three drugs showed the highest effect on ILS. In conclusion, it is suggested that FEP chemotherapy is useful for advanced gastric cancer. PMID- 3112440 TI - [Clinical experience of 8MHz RF hyperthermia with radiotherapy of cancer of the uterine cervix]. AB - During the period from September, 1983 to December, 1985, 12 patients with cancer of the uterine cervix were treated with 8MHz RF local hyperthermia, combined with radiotherapy. Out of 7 advanced cases, 3 achieved CR, 3 PRa (80-100% regression) and 1 PRb (50-80% regression) and out of the 5 cases with the recurrent cases, the results were: 3 PRa, 1 PRb, and 1 NC. It is worth noting that CR was obtained in huge tumors which are unable to be controlled by radiotherapy alone. In 3 cases, pain was experienced on the pubic bone, and in 3 other cases, skin burns, Grade II or III, occurred as complications. PMID- 3112442 TI - [Microangiopathic hemolytic anemia (MAHA) observed after administration of mitomycin C (MMC)]. AB - An autopsy case of MAHA induced by MMC is reported. The patient received MMC and tegafur following operation for colon adenocarcinoma. Five months after the operation, the patient developed MAHA, thrombocytopenia, and renal impairment. MAHA was exacerbated by blood transfusions and he died of extensive pulmonary edema. Autopsy findings showed no residual carcinoma but microangiopathies of the kidney, such as fibrinoid necrosis of the small arteries, arterioles, and glomerular capillaries, and intimal proliferation in the small arteries were evident. As renal impairment is usually irreversible in MAHA by MMC, careful follow-up of renal function should be emphasized in patients receiving MMC. PMID- 3112441 TI - [Effective radiation therapy of two cases of primary Ewing's sarcoma of the rib]. AB - Two cases of primary Ewing's sarcoma of the rib are reported, in which radiation therapy was quite effective. Case 1 was an 18-year-old female who had had an operation and radiation therapy for Ewing's sarcoma of the left 7th rib. She was referred to our hospital after a recurrent tumor was found. Radiation therapy (tumor dose 46.2 Gy) and chemotherapy were given. The tumor disappeared and there has been no relapse for 1 year and 3 months after the treatment. Case 2 was a 2 year-old-infant. Radiation therapy (tumor dose 74 Gy) was given for primary Ewing's sarcoma of the left 6th rib. The tumor became small and was successfully removed at operation. There has been no relapse or distant metastasis for 8 months following the operation. We emphasize the importance of multidisciplinary treatment in case 1 and the usefulness of preoperative radiotherapy in case 2. PMID- 3112443 TI - [Abnormality of blood coagulation in idiopathic thrombocytopenic purpura (ITP)]. PMID- 3112444 TI - [Factor VIII]. PMID- 3112445 TI - [Molecular structures and functions of coagulation and fibrinolytic factors]. PMID- 3112446 TI - [Tissue-type plasminogen activator (t-PA)]. PMID- 3112447 TI - [Factor VIII and IX inhibitors]. PMID- 3112448 TI - [Studies on application of anticoagulants for the platelet counting of the patient with pseudothrombocytopenia]. PMID- 3112449 TI - [Clinical evaluation of serum apolipoprotein A-I, A-II and B levels in patients with diabetes mellitus]. PMID- 3112450 TI - [Nutritional assessment and its parameters]. PMID- 3112451 TI - [New parameters for nutritional assessment]. PMID- 3112452 TI - [Nutritional assessment in medical patients]. PMID- 3112453 TI - [Abnormal plasminogen and thrombosis]. PMID- 3112454 TI - [Clinical usefulness of positron emission tomography in the evaluation of regional cerebral blood flow and cerebral oxygen metabolism under glycerol and carbon dioxide loadings]. PMID- 3112455 TI - [Perioperative autotransfusion for massive bleeding in a redo open heart patient with rare blood type]. PMID- 3112456 TI - [Clinical and experimental studies of the pathogenicity of Enterococcus faecalis in the urinary tract]. PMID- 3112457 TI - [Experimental studies in acute ischemic renal failure]. PMID- 3112458 TI - Thrombolytic function and extrinsic fibrinolysis in the domestic chicken. PMID- 3112460 TI - [Development of bioartificial pancreases]. PMID- 3112459 TI - Antigenic properties of Theileria sergenti in ELISA serodiagnosis. PMID- 3112461 TI - [Transplantation of purified cells from the islands of Langerhans]. PMID- 3112463 TI - [Bioinstrumentation and the nurse. IV. Nursing management for the long-term hemodialysis patient]. PMID- 3112462 TI - Comparative study of argon, Nd: YAG and CO2 lasers to achieve similar histological changes in ddY mouse skin. PMID- 3112464 TI - [Biorhythmologic analysis of the dynamics of indices of pulmonary ventilation during orthostatic manipulations]. AB - Pulmonary ventilation parameters (breathing depth, frequency and minute volume, and alveolar ventilation) of 5 healthy male test subjects who performed a 20 minute tilt test were analyzed. During tilt tests the above parameters showed oscillations in a range of about 1 minute. During the first 1-3 minutes of exposure the parameters exhibited an accentuated synchronization of the oscillations and the phenomenon of "general autonomic switch-over" with the negative phase (fall of the parameters under study below the baseline level after an initial increase above the baseline level). From the 4th minute till the 6.5th minute the function of individual components of the pulmonary ventilation system mismatched and the respiration efficacy fell. Thereafter this synchronization of the processes studied returned to the normal. Adequate adaptation of pulmonary ventilation to tilting developed not earlier than during the 13-14th minute. PMID- 3112465 TI - [Correction of hypocapnia in hypoxic humans using biofeedback of alveolar carbon dioxide pressure]. AB - Reactions of the respiratory system to the inhalation of a hypoxic gas mixture were compared when the test subjects (young healthy men) practised normal breathing or breathing with a stable alveolar PCO2. In the latter case the test subjects controlled their lung ventilation using the biofeedback technique. In this manner hyperventilation and related hypocapnia were eliminated. The possibility of practical application of biofeedback to the control of man's respiration in situations that may cause hypocapnia is discussed. PMID- 3112466 TI - Non-steroidal inhibition of granulosa cell aromatase activity in vitro. AB - Treatment of cyclic rats with the substituted triazole R151885 (1,1-di (4 fluorophenyl)-2-(1,2,4-triazol-1-yl)-ethanol causes delayed ovulation with suppressed blood oestradiol levels. To determine if R151885 can exert a direct action on ovarian oestrogen biosynthesis, we studied its effect on steroidogenesis in granulosa cell cultures from prepubertal rat ovaries. The cells were incubated for 48 h in medium containing 100 ng human FSH/ml and 10(-7) M testosterone to induce steroidogenic enzymes. When R151885 was also present in the culture medium, there was a marked and concentration-dependent reduction in granulosa cell oestradiol production. Inhibition was half-maximal at approx 3 X 10(-7) M and almost complete at 10(-5) M R151885. Progesterone and 20 alpha hydroxy-4-pregnen-3-one production were unaffected except by the highest concentration of the substituted triazole (36% inhibition at 10(-5) M). Direct assessment of aromatase activity in the 48-h cultured monolayers (oestradiol formation during a 3-h incubation with 10(-7) M testosterone) was made to determine if the inhibitory effect of R151885 was due to reduced aromatase induction/activation. This was not the case, since cells cultured in the presence of 10(-6) or 10(-5) M R151885 had levels of aromatase up to 60% higher than those cultured in its absence. To determine acute effects of R151885 on testosterone (10(-7) M) aromatization, 3-h incubations were carried out using granulosa cell suspensions with high extant aromatase activity due to stimulation by ovine FSH (100 micrograms sc, twice daily for 2 days) in vivo. The triazole acted as an apparent competitive aromatase inhibitor (apparent Km for testosterone 2.5 X 10( 8) M in the absence of R151885 rising to 4.4 X 10(-8) M in the presence of 10(-7) M R151885). Its potency as an aromatase inhibitor was approximately 10 times greater than that of the naturally occurring steroidal aromatase inhibitor 5 alpha-dihydrotestosterone. Various structurally related substances proved to be even more potent aromatase inhibitors than R151885. The most active were also substituted 4,4'-difluorophenyl derivatives containing an imidazolyl or pyridyl moiety instead of the 1,2,4-triazolyl substituent in R151885. This study has identified a novel series of nonsteroidal substances which have the characteristics of potent and specific inhibitors of testosterone aromatization by rat granulosa cells in vitro. PMID- 3112468 TI - Cooxidation of steroidal and non-steroidal estrogens by purified prostaglandin synthase results in a stimulation of prostaglandin formation. AB - Estrone (E1), estradiol (E2), the catechol estrogens 2-OHE1 and 2-OHE2, and diethylstilbestrol (DES) were incubated with purified prostaglandin synthase (PHS) in vitro in the presence of arachidonic acid and their PHS-catalyzed cooxidation was determined. 2-OHE1, 2-OHE2, and DES were extensively metabolized by PHS peroxidase activity, E1 and E2 to a lesser extent. The cooxidation of the estrogens is accompanied by an increased prostaglandin formation and an increase in cyclooxygenase activity in vitro; progesterone and nylestriol are without effect. Prostaglandins have been proposed to play a role in events related to early estrogen action in tissues such as the uterus. The cooxidation of estrogens and their metabolites by prostaglandin hydroperoxidase might represent one type of interaction between the hormones and the arachidonic acid cascade that could lead to changes in prostaglandins. PMID- 3112469 TI - Stimulation of estradiol-17 beta secretion by 7,12-dimethylbenz (a) anthracene during mammary tumor induction in Sprague-Dawley rats. AB - Testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, estrone and estradiol-17 beta serum levels were measured at given times after dimethylbenz (a) anthracene (DMBA) treatment of a sensitive rat strain Sprague-Dawley (S-D) and a resistant strain Wistar (W). Tumors appeared with a 100% incidence around the 14th to 15th estrous cycle after DMBA treatment in in Sprague-Dawley rats. Hormonal determinations were made, during the 5th or 6th estrous cycle after DMBA treatment, in groups of 4-day cycling rats of both strains which were given DMBA or the carrier solution (sesame oil) when they were about 55-days old. In Sprague Dawley female rats, DMBA treatment significantly stimulated estradiol-17 beta and estrone preovulatory surge on proestrous days. No such stimulation was found for any other steroid at any time of the estrous cycle. On the other hand, the resistant Wistar rats did not show any disturbed preovulatory or basal steroid hormone release after the carcinogen treatment. These results complete and explain previous findings concerning the hypothalamo-pituitary activity after DMBA treatment of S-D rats: an early and persistent alteration in the centers involved in the hormonal cyclicity of the hypothalamo-pituitary-ovarian axis must be a result of the DMBA treatment. This deregulation could probably account for the distant and selective production of tumors in the mammary gland induced by a single gastric administration of DMBA. PMID- 3112467 TI - A possible role for dephosphorylation in glucocorticoid receptor transformation. AB - Addition of bovine intestinal alkaline phosphatase to mouse AtT-20 cell cytosol increases the rate of glucocorticoid receptor transformation, as evidenced by a change in sedimentation rate from 9.1S to 5.2S. Acid phosphatases are completely ineffective in this regard. Alkaline phosphatase-promoted receptor transformation is both time- and dose-dependent. A variety of phosphatase inhibitors are effective in inhibiting this process, the most potent being transition metal oxyanions such as molybdate, tungstate, and arsenate. The ability of the various inhibitors to suppress alkaline phosphatase-promoted receptor transformation does not correspond well with their potencies for inhibiting para-nitrophenyl phosphate hydrolysis. However, a better correspondence between the inhibition of endogenous receptor transformation and total cytosolic phosphatase activity is observed, and both sodium fluoride and glucose-1-phosphate inhibit endogenous receptor transformation. The protease inhibitors phenyl-methylsulfonyl fluoride and antipain have no effect on receptor transformation. Surprisingly, leupeptin is effective in inhibiting alkaline phosphatase-promoted receptor transformation. Although this raises the possibility of a contaminating protease activity in the alkaline phosphatase enzyme preparation, treatment of covalently affinity-labeled receptor with the enzyme shows no proteolysis of the receptor or any other non specifically labeled cytosolic protein. Thus, it is possible that a novel action of leupeptin, unrelated to its protease-inhibitory activity, may be involved in the suppression of receptor transformation. The studies presented here suggest that dephosphorylation of some component in cytosol is involved in the destabilization of receptor subunit interactions, resulting in glucocorticoid receptor transformation. PMID- 3112470 TI - A sensitive bridge heterologous enzyme immunoassay of progesterone using geometrical isomers. AB - A sensitive bridge heterologous enzyme immunoassay of progesterone using geometrical isomers of progesterone 3(O-carboxymethyl)oxime(E/Z) was developed. Isomers were separated by synthesis of N-hydroxysuccinimide esters. Progesterone 3(Z)(O-carboxymethyl)oxime N-hydroxysuccinimide ester bound with beta galactosidase in an appropriate molar ratio provided a conjugate suitable for an enzyme immunoassay. The antiserum was raised in rabbits by immunizing the animals with the progesterone 3(E)(O-carboxymethyl)oxime-bovine serum albumin conjugate. This bridge heterologous enzyme immunoassay proved to have sufficient sensitivity equivalent to radioimmunoassay and excellent specificity. PMID- 3112471 TI - Method for stimulating the adrenergic system of an isolated perfused rat heart. AB - A method is presented whereby isolated perfused rat hearts can be rapidly prepared for the stimulation of chronotropic activity by electrical pulses or exogenous noradrenaline. The mediation of the response by sympathetic nerves is demonstrated through modulation of the response by compounds with established pharmacological actions. Propranolol inhibits the increase in heart rate to both electrical stimulation and exogenous noradrenaline, whereas bretylium inhibits only electrically induced increases. Chronic pretreatment with 6-hydroxydopamine decreases the response to electrical stimulation but increases that to exogenous noradrenaline. PMID- 3112472 TI - JM, a Thy-ALL cell line produces both inhibitory and stimulatory lymphokines for bone marrow progenitor cells. AB - Normal and malignant T cells as well as T-cell hybridomas have frequently been reported to produce factors which stimulate the growth of committed hemopoietic progenitors. One previous report described a lymphokine produced by a T-cell clone which inhibited hemopoietic progenitor cell proliferation. We now describe the simultaneous production of two activities by a Thy-ALL cell line (JM), a sub line of Jurkat. Two sets of culture conditions were used: the Fauser & Messner and Iscove's assays. We have been able to separate both inhibitory and stimulatory factors for the growth of multipotent and committed bone marrow progenitors (CFU-GEMM, BFU-E, CFU-E and CFU-GM). The stimulatory factor has an apparent mol. wt of less than 30,000 and the inhibitor an apparent mol. wt of 65 80,000. The growth promoting activity for BFU-E and CFU-GEMM could replace that of phytohemagglutinin stimulated leucocyte conditioned medium (PHA-LCM). We do not know if the production of both activities is due to the malignant phenotype or if there is a normal counterpart to JM that could produce both inhibitory and stimulatory factors. PMID- 3112473 TI - [Fabry's disease]. PMID- 3112474 TI - [Clinical and epidemiologic study of diabetic ketoacidosis. Importance of primary care]. PMID- 3112475 TI - [Diabetic ketoalkalosis]. PMID- 3112476 TI - [Acute pancreatitis in adolescents: a critique]. PMID- 3112477 TI - [Beta lactamase-producing Neisseria gonorrhoeae. Data of the Nuestra Senora del Mar General Hospital in Barcelona]. PMID- 3112478 TI - Circling in normoxic or hypoxic rats with unilateral 6-OHDA nigrostriatal lesion. Part 2. Effects of d-amphetamine. AB - Unilateral administration of 6-hydroxydopamine into the rat nigrostriatal system induces a unilateral damage of the dopamine (DA) containing neurons. In such lesioned animals, d-amphetamine (AMPH) induces circling behavior (ipsiversive circling) in relation to its DA releasing property in the non-lesioned side. A preexposition to hypoxia potentiates the behavioral effect of AMPH: this can be related to an increase in the amount of substrate available for release, dopamine. Hypoxia occurring just after the administration of AMPH does not initially modify the AMPH induced circling behavior. This suggests that tyrosine hydroxylase inhibition by hypoxia is not a limiting factor of the releasing effect of AMPH. After 20 min of hypoxia, circling decreases. This impairment could be mediated by a decrease of the amount of available DA and/or by a decrease of release. PMID- 3112479 TI - [Severely demented patients with serious eating problems: supplemental feeding or not--a question of outlook on life]. PMID- 3112480 TI - [Symptoms of Recklinghausen's disease in the field of ENT medicine]. AB - Neurofibromatosis (also known as multiple neuroma and Recklinghausen's disease) is caused by a deficient proliferation of the neuroectodermal and mesodermal crest. Therefore, a wide variety of symptoms can be found including cutaneous, neurological, ophthalmological, visceral and osseous changes. Hallmark of this disease are so-called cafe-au-lait areas of pigmentation, or spots. The ENT specialist is confronted with bilateral acoustic tumours, peripheral nerve tumours, cutaneous tumours, tumours of the larynx and alterations of the facial bones. Eight cases of neurofibromatosis are demonstrated, and recent literature is discussed. Management of patients suffering from neurofibromatosis is mainly palliative and symptomatic. To achieve a good result in treatment there must be an effective cooperation between specialists of different disciplines. PMID- 3112481 TI - Experimental study of CO2-laser-induced histological effects on human fallopian tube: determination of CO2 laser parameters to be used in microsurgery. AB - This experiment investigates CO2-laser-induced histological effects on fallopian tubes obtained during hysterectomies in women. Tubal transversal sections were performed at isthmic and ampullar sites. Forty strips were available for histological study of the cut section area. The role of different parameters such as radiation power and beam fractionation (continuous versus pulsed) on tissue lesions was assessed. In tubal microsurgery, the CO2 laser can be used as a scalpel with the predominant advantage of minimal tissular alterations. As a result of this study, our recommended parameters are the following: radiation power, 7-10 W; beam focalization zone, 0.2 mm; energy density, 20,000-35,000 W/cm2; continuous operation; moving speed, 1 cm/s. PMID- 3112482 TI - M-chlorophenylpiperazine increases blood pressure and heart rate in pithed and conscious rats. AB - In pithed rats, m-chlorophenylpiperazine (m-CPP) produced marked, dose-dependent (ED50 = 0.18 mumol) increases in mean arterial blood pressure which peaked within 1 minute and were sustained over 15 minutes. Two serotonin antagonists, metergoline and ritanserin, completely blocked the pressor responses to 2.5 mg/kg m-CPP in pithed adrenal demedullated rats, while alpha-adrenergic blockade by prazosin plus yohimbine was without effect, suggesting that the doubling in blood pressure produced by m-CPP was mediated via serotonin receptors within blood vessels. Somewhat smaller increases in blood pressure over baseline values were observed after m-CPP administration to conscious, freely moving rats. A small but statistically significant increase in heart rate peaked 5 minutes after m-CPP and also was blocked by metergoline but was only minimally affected by ritanserin or the prazosin-yohimbine combination. These results with m-CPP support other evidence for two or more separable effects of serotonergic agonists on the peripheral cardiovascular system. PMID- 3112483 TI - Determination of monoamines by use of liquid chromatography with electrochemical detection in the study of selective monoamine neurotoxins. AB - Determination of regional monoamine levels in the CNS in the study of the effects of selective monoaminergic neurotoxins is a reliable method with which to study the morphological changes in denervated as well as re- or hyperinnervated regions as evidenced by comparisons with several other methods. In the acute stage, the changes in monoamine levels reflect both the beginning of the degeneration and the acute pharmacological effects exerted by several monoaminergic neurotoxins. The only exception to this seems to be the MPTP-induced chronic decrease of DA in the nucleus accumbens and the tuberculum olfactorium where no morphologic changes have been found so far. PMID- 3112484 TI - Lipid peroxidation in erythrocyte membranes: cholesterol product analysis in photosensitized and xanthine oxidase-catalyzed reactions. AB - The effects of singlet oxygen- and oxygen radical-induced lipid peroxidation on cell membrane integrity were compared, using the human erythrocyte ghost as a model system. Resealed ghosts underwent lipid peroxidation and lysis (release of trapped glucose-6-P) when irradiated in the presence of uroporphyrin (UP) or when incubated with xanthine (X), xanthine oxidase (XO) and iron. The UP-sensitized process was inhibited by azide but not by phenolic antioxidants, consistent with singlet oxygen (nonradical) involvement. This was confirmed by showing that the predominant photoproduct of membrane cholesterol was the 5 alpha-hydroperoxide. Total hydroperoxide (LOOH) content in UP-photooxidized ghosts increased linearly during the prelytic lag and throughout the period of rapid lysis. Unlike the photoreaction, X/XO/iron-dependent peroxidation and lysis was inhibited by catalase, superoxide dismutase and phenolic antioxidants, indicating O2-/H2O2 intermediacy and a free radical mechanism. Correspondingly, only radical reaction products of cholesterol were formed, notably the 7 alpha-, 7 beta-hydroperoxide pair. Membrane lysis had a distinct lag as in photooxidation; however, the LOOH profile was more complex, with an initial lag followed by a sharp increase and then slow decline. X/XO/iron-induced lysis commenced when LOOH levels were 2-3 times higher than in photosensitized lysis, suggesting that the pathways of membrane lesion formation are different in the two systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112485 TI - Analysis of lipids containing hydroxy fatty acids. AB - Lipids containing hydroxy fatty acids or hydroxyacyl moieties are acetylated with [1-14C]acetic anhydride or [3H]acetic anhydride, and the content of hydroxy fatty acids or hydroxyacyl moieties is estimated from the specific radioactivity of the acetylated products with respect to that of radioactive standards, such as radioacetylated ricinoleic acid or triricinoleoylglycerol. Mixtures of triacylglycerols containing one, two and three hydroxyl groups per molecule are derivatized in a similar manner, and the resulting acetates are fractionated by thin layer chromatography according to the number of acetate groups per molecule. The relative proportion of each type of triacylglycerols in the mixture is estimated from the distribution of radioactivity in the various fractions. Applications of these techniques are demonstrated by the analysis of several seed lipids. PMID- 3112486 TI - Medium chain triglycerides and structured lipids. AB - Lipids are an essential component of our body composition and necessary in our daily food intake. Conventional fats and oils are composed of glycerides of long chain fatty acids and are designated as long chain triglycerides (LCT). Body fat as well as the fats and oils in our daily intake fall into this category. In enteral and parenteral hyperalimentation, we can identify such LCT fats and oils. Soy, corn, safflower and sunflowerseed oils are typical of the LCT oils. In the search for alternative noncarbohydrate fuels, medium chain triglycerides (MCT) are unique and have established themselves in the areas of malabsorption syndrome cases and infant care and as a high energy, rapidly available fuel. Structure lipids with a MCT backbone and linoleic acid built into the triglyceride molecule have been developed to optimize the triglyceride structure that is best for patients, particularly the critically ill. Structured lipids with built-in essential fatty acid components or other polyunsaturated fatty acids promise greater flexibility in patient care and nitrogen support. PMID- 3112487 TI - Medium chain triglycerides and structured lipids as unique nonglucose energy sources in hyperalimentation. AB - This brief review will discuss recent work concerning new intravenous lipid emulsions for future use in clinical patients. Intravenous lipid emulsions currently available in the United States are derived from soybean or safflower oils and serve as sources of nonglucose, nitrogen-sparing calories and the essential fatty acid linoleic acid. Because of concerns that much of the infused long chain triglyceride is not oxidized readily and that there may be some immune system impairment, newer emulsions utilizing medium chain triglycerides have been developed. PMID- 3112490 TI - Home equity conversions as alternatives to health care financing. PMID- 3112489 TI - Possible infectious causes in 651 patients with acute viral hepatitis during a 10 year period (1976-1985). AB - Six hundred and fifty-one patients with acute viral hepatitis were identified serologically between January 1976 and December 1985. Of these, 109 (17%) had hepatitis A, 135 (21%) had hepatitis B, and 407 (62%) had hepatitis non-A, non-B. The possible infectious causes for acquisition of viral hepatitis occurring within 6 months before the onset of hepatitis were analysed. Approximately 80% of cases of hepatitis A and 70% of hepatitis B had no known risk factor, while in 67% of cases of hepatitis non-A, non-B possible risk factors for infection were documented. Infectious causes for hepatitis A were ingestion of raw shellfish (11%) and previous familial contact with patients with hepatitis A (10%). For hepatitis B, risk factors included medicare (24%), such as transfusion, surgical operation, accidental needle stick and acupuncture, and sexual contact (6%). For hepatitis non-A, non-B, the most important infectious cause was medical procedures (65%). The numbers of hospital employees were 2 (2%) with hepatitis A, 15 (11%) with hepatitis B and 14 (3%) with hepatitis non-A, non-B. These data suggest that hepatitis non-A, non-B can be a kind of nosocomial disease. PMID- 3112491 TI - Wrongful life decision in Israel. Civil appeal 518/82, 540/82. PMID- 3112488 TI - The influence of dietary medium chain triglycerides on rat mammary tumor development. AB - The N-nitrosomethylurea rat mammary tumor model was used to compare the tumor promoting effects of a high-fat (HF) diet containing a 3:1 mixture of medium chain triglycerides (MCT) and corn oil with that of a HF and a low-fat (LF) corn oil diet. The serum and tumor lipid content and fatty acid (FA) composition were also determined in the three dietary groups. It was found that the MCT-containing diet failed to promote tumor development compared with the HF corn oil group. Tumor incidence in the HF-MCT group was similar to that of the LF corn oil group (5% fat, w/w), but significantly decreased compared to the HF corn oil group. Total serum cholesterol levels were significantly depressed in the HF corn oil group compared to the HF-MCT and LF corn oil groups. Analysis of serum and tumor FA profiles indicated that the HF corn oil group exhibited approximately twice the amount of linoleic acid (LA) as the other two treatment groups. Differences among the three groups in the major FA metabolite of LA, arachidonic acid, were minimal. These results are consistent with the hypothesis that tumor promotion by dietary fat is more a function of the type than the amount of fat ingested. In addition, they indicate that MCT, due at least in part to their unique structural and physiological properties, exert markedly different effects on mammary tumor development than conventional long chain unsaturated fatty acids. PMID- 3112492 TI - Access to prenatal care and prevention of low birth weight. PMID- 3112493 TI - More pointers on PKU. PMID- 3112495 TI - Intravenous immune globulin for treating primary immunodeficiency disease. PMID- 3112494 TI - Pertussis vaccine. PMID- 3112496 TI - How well do adolescents mother? PMID- 3112498 TI - Helping mothers integrate the birth experience. PMID- 3112497 TI - Tracheostomy care: parents as learners. PMID- 3112499 TI - How to evaluate breast pumps. PMID- 3112500 TI - Pediatric resuscitation: mock code. PMID- 3112501 TI - Are commercial patient education materials right for you? PMID- 3112502 TI - When parents refuse to consent. PMID- 3112503 TI - The concept of significance. PMID- 3112504 TI - How much quality control is enough? A cost-effectiveness model for clinical laboratory quality control procedures (illustrated by its application to a ligand assay-based screening program). AB - Quality assurance testing represents a substantial proportion of the clinical laboratory budget, but current guidelines are based on criteria that pertain to analytic error rather than to optimization of the cost-effectiveness of patient care. A general Bayesian mathematical model for the cost-effectiveness of assay quality control has been developed, and is demonstrated using previously published data. The cost-effectiveness of quality assurance as defined here depends upon the prevalence of disease, the shapes of the distributions of test results observed in the non-diseased and diseased populations, the decision limit selected for labeling results positive or negative, the costs and benefits associated with each of the possible therapeutic outcomes, the magnitude of random and systematic analytical errors, the statistical power of the quality control test in use, the costs associated with delays due to re-assay, and the proportion of total test cost attributable to quality control procedures. Given current clinical laboratory practice, much of this information will not be routinely available. The model combines these factors into a simple equation with three terms: one for the cost of the original and any required repeat laboratory analyses, one for the cost of delay entailed by the rejection of an assay batch, and one for the change in total costs consequent to rejection of erroneous assay results. PMID- 3112505 TI - [Parenteral feeding of newborn infants]. PMID- 3112506 TI - [The KEP-1 enteral feeding system for tube hyperalimentation of seriously ill patients]. AB - The KEP-1 system is designed for tube hyperalimentation of patients, including burn patients. It consists of a four-channel peristaltic pump and a liquid food mixer tank. The results of clinical testing are given. PMID- 3112507 TI - A new tool for continuous detection of the presence of triatomine bugs, vectors of Chagas disease, in rural households. PMID- 3112508 TI - Molecular biology of tissue plasminogen activator and endogenous inhibitors. PMID- 3112509 TI - Production and characterization of the extracytoplasmic portion of the human interleukin-2 receptor. AB - We made a mutant cDNA clone of the human interleukin-2 (IL-2) receptor by introducing a termination codon at the eighth amino acid residue upstream from the putative transmembrane region. Ltk- cells were transfected by this mutant cDNA and cell-lines secreting the extracytoplasmic portion of the IL-2 receptor were established. The artificial secretory molecule of the IL-2 receptor named "bottom-less" receptor was able to react with anti-Tac antibody and to bind IL-2. We purified the bottom-less receptor to homogeneity by affinity chromatography using an IL-2-Sepharose column. The affinity (Kd value) of the 125I-labeled bottom-less receptor to IL-2 coupled to Sepharose beads was estimated to be 4.5 microM. All these results confirm the putative membrane topology of the IL-2 receptor based on the primary structure, and suggest that the bottom-less receptor may maintain the basic structure and function of the extracytoplasmic portion of the IL-2 receptor. PMID- 3112511 TI - Behavior of triatomines (Hemiptera: Reduviidae) vectors of Chagas' disease. II. Influence of feeding, lighting and time of day on the number of matings, mating speed and duration of copulation of Panstrongylus megistus (Burm, 1835) under laboratory conditions. AB - To determine the influence of feeding, lighting and time of day on the copulating behavior of Panstrongylus megistus, 480 insect pairs were divided into four groups of 120 each and tested in the following respective situations: without food deprivation (F.D.), with five days of F.D., with ten days of F.D., and with 20 days of F.D. The tests were performed between 9:00 a.m. to 12:00 a.m. and 7:00 p.m. to 10:00 p.m., with light (700-1400 lux) and in the dark (1.4-2.8 lux) and behavior was recorded by the time sampling technique. Mating speed (MS) and duration of copulation (DC) were also calculated for each situation. The maximum frequency of copulation was observed after five days of F.D., at night, in the dark (n = 16), and the minimum was observed for recently-fed pairs, at night, with light (n = 4). Males approached females more often than females approached males. MS was lowest in pairs with twenty days of F.D., at night, with light (mean = 23.0 +/- 16.0 minutes), and highest in recently-fed pairs, during the day, with light (mean = 2.9 +/- 2.5 minutes). DC was shortest in recently-fed insects, during the day, in the dark (mean = 23.5 +/- 6.7 minutes), and longest in recently-fed animals, at night, in the dark (mean = 38.3 +/- 6.9 minutes). PMID- 3112510 TI - Immunoglobulin heavy chain and T-cell receptor gamma and beta chain gene rearrangements in acute myeloid leukemias. AB - Somatic rearrangements of immunoglobulin (Ig) and T-cell receptor (TCR) genes are the basis for the production of receptors for antigen in B-cells and T-cells, respectively. Here, we have studied the extent and pattern of rearrangements at Ig and TCR loci in 17 patients presenting with acute myeloid leukemia (AML). Our data demonstrate illegitimate clonal rearrangements at Ig heavy and/or TCR beta chain genes in 5 of 17 AML patients. In four of these five patients, rearrangements at the TCR beta chain gene locus were also observed. Seven patients displayed clonal TCR gamma chain gene rearrangements as the only abnormality. Rearrangements at Ig light chain and TCR alpha chain gene loci were not detected. Illegitimate TCR gamma chain gene rearrangements in AML involve recombinations of only a subset of V gamma genes, predominantly with the J gamma 1 region. Rearrangements at the TCR beta chain gene locus are characterized by both D-J and V-D-J recombinations, with predominant use of the J beta 1 region. The absence or presence of illegitimate antigen receptor gene rearrangements in AML may constitute a prognostic marker. In addition, these alterations can be used to establish clonality in AML with direct applications in the monitoring of disease. Finally, the present data relate to the problem of lineage assignment of acute leukemias based on Ig and TCR gene rearrangements and strongly suggest that the latter cannot be regarded as unequivocal evidence for the B-cell or T-cell lineage, respectively. PMID- 3112512 TI - Nasal secretions of Neisseria lactamica carriers have an inhibitory effect on Neisseria meningitidis attachment to human oroepithelial cells. AB - Nasal secretions of volunteers colonized by N. lactamica impaired the attachment of N. lactamica and of meningococci of groups A and B to oroepithelial cells. Bacterial adherence was found to be mediated by nonpiliated adhesins with antigen(s) which probably are shared by the strains tested. Although a strong attachment-inhibiting activity arises in their nasal secretions, volunteers remained colonized by N. lactamica. This evidence suggest that the eradication of Neisseria carriage is a multifactorial event. PMID- 3112513 TI - [Variability of Schistosoma mansoni strains in cercariae production]. AB - A preliminary study showed that B. glabrata infected with strains of S. mansoni isolated from patients with the hepatosplenic form of the disease produced a higher number of cercariae and died sooner than those infected with strains from the intestinal and hepatointestinal forms. However, further studies showed a great variation of the number of cercariae produced by some of those strains in the same system, without relation with the clinical form of the disease. PMID- 3112514 TI - Expenditures and sources of funds for mental health organizations, United States, 1983. PMID- 3112515 TI - Mutations affecting translation of the bacteriophage T4 rIIB gene cloned in Escherichia coli. AB - Mutant ribosome binding sites of the bacteriophage T4 rIIB gene, resident on an 873 bp DNA fragment, were cloned into a plasmid vector as in-frame fusions to a reporter gene, beta-galactosidase. The collection of mutations included changes in the region 5' to the Shine/Dalgarno sequence, a mutation of the Shine/Dalgarno sequence, the alternate initiation codons GUG, AUA and ACG, and mutants in which several closely spaced initiation codons compete with each other on the same mRNA. The results show that the secondary structure variations we have installed 5' to the Shine/Dalgarno sequence have little effect on translation. GUG is essentially as good an initiator of translation as AUG when they are assayed on separate messages, but is outcompeted at least 50-fold in the sequence AUGUG. AUA and ACG are poor start codons, and are temperature sensitive. The initiation codon pair AUGAUA, in which the AUG is only two nucleotides from the Shine/Dalgarno sequence, displays a novel cold-sensitive phenotype. PMID- 3112517 TI - Expression of the Bacillus subtilis polC gene in Escherichia coli. AB - We have cloned a 14 kb DNA segment containing the coding sequence (polC) for DNA polymerase III (PolIII) from the Bacillus subtilis chromosome. The plasmid carrying the sequence, pRO10, directs the synthesis of the 160 kDa PolIII protein and three additional polypeptides in Escherichia coli maxicells from strain CSR603. A set of deletion derivatives of pRO10 was constructed in vitro. The location of the PolIII coding sequence and the direction of transcription through the polC gene were determined by analysis of the truncated polypeptides observed in extracts of CSR603 transformants. Two HindIII segments subcloned from pRO10 were found to contain promoter sequences which function in E. coli and in vegetative phase B. subtilis cells. The location of the promoter sequence was determined with respect to the polC gene. The B. subtilis polC gene did not complement the temperature-sensitive defect of an E. coli PolIII mutant (dnaE486). The presence of the complete B. subtilis polC gene on a multicopy plasmid inhibited the growth of E. coli cells. PMID- 3112516 TI - A general method for the construction of Escherichia coli mutants by homologous recombination and plasmid segregation. AB - A technique is presented by which mutations can be introduced into the Escherichia coli chromosome by gene replacement between the chromosome and a plasmid carrying the mutant gene. The segregational instability of plasmids in E. coli is used with high efficiency to isolate E. coli mutants. The method should be applicable to construction of mutants for any E. coli chromosomal gene provided it is dispensable, and for any E. coli strain provided it is capable of homologous recombination. The use of the method was demonstrated by constructing E. coli mutants for the glycogen branching enzyme gene (glgB) and the beta galactosidase gene (lacZ). The results show that recombination occurs via a reciprocal mechanism indicating that the method should, in a slightly modified form, also be useful in transferring chromosomal mutations onto multicopy plasmids in vivo. PMID- 3112518 TI - Dependence of expression of an inducible Staphylococcus aureus cat gene on the translation of its leader sequence. AB - The gene for chloramphenicol (Cm) acetyltransferase (CAT) carried by the staphylococcal plasmid pUB112, whose expression can be stimulated by Cm, is preceded by a regulatory region containing two control elements. One of these consists of a Shine-Dalgarno (SD) sequence followed by an open reading frame coding for a leader peptide of nine amino acids. Previous work has shown that the SD sequence is essential for inducibility of Cm resistance by the antibiotic (Bruckner and Matzura 1985). Here we demonstrate that fusion of the leader peptide coding sequence to a truncated 'lacZ gene results in synthesis of a leader peptide-beta-galactosidase fusion protein. Introduction of an ochre nonsense codon into the reading frame of the leader peptide sequence leads to considerable reduction of the basal expression and loss of inducibility of the cat gene. These results reveal that synthesis of the leader peptide is required for the basal and inducible expression of the cat gene and support the model of translational attenuation for its regulation. PMID- 3112519 TI - Characterization of the levanase gene of Bacillus subtilis which shows homology to yeast invertase. AB - The structural gene for the enzyme levanase of Bacillus subtilis (SacC) was cloned in Escherichia coli. The cloned gene was mapped by PBS1 transduction near the sacL locus on the B. subtilis chromosome, between leuA and aroD. Expression of the enzyme was demonstrated both in B. subtilis and in E. coli. The presence of sacC allowed E. coli to grow on sucrose as the sole carbon source. The complete nucleotide sequence of sacC was determined. It includes an open reading frame of 2,031 bp, coding for a protein with calculated molecular weight of 75,866 Da, including a putative signal peptide similar to precursors of secreted proteins found in Bacilli. The apparent molecular weight of purified levanase is 73 kDa. The sacC gene product was characterized in an in vitro system and in a minicell-producing strain of E. coli, confirming the existence of a precursor form of levanase of about 75 kDa. Comparison of the predicted aminoacid sequence of levanase with those of the two other known beta-D-fructofuranosidases of B. subtilis indicated a homology with sucrase, but not with levansucrase. A stronger homology was detected with the N-terminal region of yeast invertase, suggesting the existence of a common ancestor. PMID- 3112521 TI - Genetic mapping by means of protoplast fusion in Bacillus subtilis. AB - A new mapping method involving protoplast fusion in Bacillus subtilis is described. Protoplasts from an isogenic standard marker strain containing purA and from a strain containing both purB and the marker, "x", to be mapped were fused with polyethylene glycol, and purA+ purB+ fusants were selected. After isolation of single colonies and determination of unselected markers, marker x was mapped between two standard markers. This method was fully applicable to PBS1 resistant strains (e.g., lyt strains). The results obtained by protoplast fusion, conventional transformation and/or lysed protoplast transformation indicated that a lyt strain, Ni15, contained two new autolysin-minus mutations (lyt-151 and lyt 152). The properties of lyt-15 are also discussed. PMID- 3112520 TI - Isolation and characterization of Streptomyces lividans mutants deficient in intraplasmid recombination. AB - Plasmid pIF132 containing two direct repeats of the mel (melanin) sequence was used to monitor intraplasmid recombination. Five mutants of Streptomyces lividans TK64 deficient in intraplasmid recombination were isolated. Four contained additional defects in aerial mycelium formation, pigmentation, and nutrient requirements; among these two showed extensive amplification of chromosomal sequences. Mutant JT46 had no pleiotropic defects but had the most severe blockage in recombination. Only one of the mutants was slightly more sensitive to UV and two were slightly more sensitive to mitomycin C. Plasmid pWCL1 (containing pIJ702, pUC12, and HBVsAg sequences; Lee et al. 1986) could not stably replicate in TK64 without spontaneous deletions. In contrast the mutant JT46 maintained the integrity of pWCL1 much more stably. PMID- 3112522 TI - Genetic analysis of mannityl opine catabolism in octopine-type Agrobacterium tumefaciens strain 15955. AB - The genetic organization of functions responsible for mannityl opine catabolism of the Ti plasmid of Agrobacterium tumefaciens strain 1,5955 was investigated. A partial HindIII digest of pTi1,5955 was cloned into a broad host range cosmid and the clones obtained were tested for ability to confer mannityl opine degradation upon Agrobacterium. Inserts containing genes for catabolism of mannopinic acid, mannopine, agropine, and agropinic acid were obtained, spanning a segment of 43 kb on the Ti plasmid. Two clones conferring upon Agrobacterium the ability to catabolize the mannityl opines were mobilized to several Rhizobium sp., to Pseudomonas putida and P. fluorescens and to Escherichia coli. The catabolic functions were phenotypically expressed in all Rhizobium sp. tested, and in P. fluorescens, but not in P. putida or in E. coli. PMID- 3112524 TI - Plasmid maintenance in Bacillus subtilis recombination-deficient mutants. AB - An isogenic set of 11 recombination-deficient mutant strains of Bacillus subtilis has been constructed. Whereas plasmid pUB110 is stably maintained in such Rec- cells, the high copy number plasmid pC194 is unstable. Instability in Rec- strains could be mostly attributed to the deleterious effect of the presence of the plasmid on the Rec- cells' growth capability. In part, instability of pC194 derivatives could also be correlated with the presence of an unusually high amount of multimeric DNA molecules. PMID- 3112523 TI - Aphidicolin-resistant mutator strains of mouse teratocarcinoma. AB - From among a series of stable, aphidicolin-resistant mutant strains of mouse teratocarcinoma, derived from a multipotent parental line (PSA-1-80), three were selected for further study on the basis of their comparatively high degrees of resistance and elevated frequencies of spontaneous forward mutation to 6 thioguanine and ouabain resistance. Fluctuation tests confirmed that they were mutator strains. Since each of the three mutants was isolated after multiple rounds of selection, and since a variety of biochemical abnormalities were observed, it is likely that a number of mechanisms, probably consisting of overlapping subsets, determine the phenotypes. Abnormalities in the metabolism of the nucleotide substrates for polymerization are likely to be of major importance in mutants designated Aph-2 and Aph-3, as there were marked alterations in the dCTP and dATP pool sizes. The specific activity of DNA polymerase alpha was also increased. For the case of Aph-3, which exhibited the greatest (400-fold) increase in resistance to aphidicolin, a mutation in the structural gene for DNA polymerase alpha may be an additional important component, since in vitro assays revealed that the isolated enzyme was resistant to aphidicolin. For the case of Aph-1 however, only minor alterations in dNTP pools were observed, and there was no increase in the specific activity of DNA polymerase alpha or in the aphidicolin resistance of the isolated DNA polymerase alpha, suggesting yet another mechanism(s) underlying the aphidicolin resistance/mutator phenotype. All three mutants formed subcutaneous tumors in syngeneic mice; both Aph-1 and Aph-2 were multipotent; whereas Aph-3 was nullipotent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112525 TI - A new mutator strain of Bacillus subtilis. AB - Bacillus subtilis strain SB1207, widely used in our laboratory, was found to be highly temperature-sensitive and to exhibit a strong SOS-independent mutator phenotype at elevated temperatures. Both chromosomal and plasmid-borne genes were affected by the mutator. Lethality and mutator phenotype could not be attributed to a replication shut off or to thymine starvation. Due to the high frequency of base misincorporation, the mutator phenotype probably results from an editing defect rather than from a post-replication defect (mismatch repair). PMID- 3112527 TI - Experimentally induced Bacteroides infections in the rabbit. AB - Rabbits were infected with Bacteroides fragilis, B. macacae and B. gingivalis in monoinfection, mixed Bacteroides infection, and mixed infection of B. gingivalis with Streptococcus faecalis, Escherichia coli and Clostridium sporogenes. Monoinfection gave rise to localised, nodular abscesses at cell levels greater than 0.5 X 10(5) cfu ml-1, the severity of which was dose related. Mixed infections including B. gingivalis caused severe spreading lesions and affected organs distant from the injection site. Histopathological studies indicate an inflammatory response with gas vacuolation and local necrosis. PMID- 3112526 TI - Cloning and expression of streptococcal pyrogenic exotoxin A and staphylococcal toxic shock syndrome toxin-1 in Bacillus subtilis. AB - The genes encoding streptococcal pyrogenic exotoxin type A (SPE A) and staphylococcal toxic shock syndrome toxin-1 (TSST-1) were stably cloned and expressed in Bacillus subtilis. In the non-pathogenic Bacillus background, the recombinant speA clone expressed 32-fold more SPE A than the native streptococcus, and similarly, the recombinant plasmid harboring tst expressed 4 fold more TSST-1 in Bacillus than in the native Staphylococcus aureus. The Bacillus-derived products were secreted into the culture fluid, were resistant to proteolytic degradation and their biological activities mimicked native preparations. PMID- 3112528 TI - Local cold exposure test for capillaroscopic examination of patients with Raynaud's syndrome. PMID- 3112529 TI - [Dynamic interaction of virulent Pseudomonas aeruginosa bacteriophages with the host bacteria]. AB - The population interactions of Pseudomonas aeruginosa virulent bacteriophages phi kF77 and phi mnF82 with host bacterial cells were studied in dynamics under the conditions of continuous cultivation in the chemostat regime with glucose limitation. Two different types of maintaining the bacterium and its specific bacteriophages in the population were detected. When P. aeruginosa was cultivated with phage phi mnF82, such a maintenance was realized due to the successive appearance of bacterial mutants resistant to the phage and of phage mutants overcoming this resistance. When P. aeruginosa was cultivated with phage phi kF77, these were maintained owing to the ability of P. aeruginosa to form unstable phage-resistant variants with the segregation of phage-sensitive cells. PMID- 3112530 TI - A membrane-specific tyrosinase chelate: the mitotic regulator? AB - Cancer's random, reversible, unstable transitions to "normal" structures imply their functional relation. Similar random, continuous, reversible oncogene "mutational transformation" also lacks a consistent hybrid. Positing cancer's "mutationally altered genotype" leads to medically foreign causes, qualities, inducers, suppressors, immune proteins, and viruses. Its random variation, however, opposes the functionally discrete, ordered, stable, irreversible hybrid variation and single-valued transforms of molecular genetics. There, "causal mutational operators" remain unspecified; only consistent single-valued DNA base and amino acid change, as "transform operand", are made explicit. A mitotically "blocked" (normal) and "unblocked" (malignant) stem cell "phenotype", operationally constructed from microscopic data, is therefore viewed within the homeostatic context of open-system enzyme-regulatory equilibrium. This functional, stochastic field distribution between "structurally bound" and "freely dividing" stem cell number discloses their putative regulatory mitotic blocking factor. A tyrosinase complex, interacting by Cu2+-Fe2+ chelation with a proline hydroxylase divisional enzyme near stem cell ribosomes, maintains steady state mitotic equilibrium. Based upon familiar medical, biochemical, and energy principles this confronts cancer's pigmentary-depigmentary signs, glycolytic metabolism, elevated serum tyrosinase, defective collagen production, exposed membrane binding sites, and tyrosine's recent growth control role. PMID- 3112531 TI - Nitrate therapy of ischaemic heart disease. PMID- 3112532 TI - [Nitrate tolerance in long-term therapy?]. PMID- 3112533 TI - [Justification for combining Bacillus subtilis with antibiotics in the therapy of diarrheal syndrome]. PMID- 3112535 TI - [Islet cell transplantation--facts and development]. PMID- 3112534 TI - [Physical endurance of patients with chronic hepatitis. The standardized treadmill test of 95 patients with liver biopsy verified disease]. PMID- 3112536 TI - Cost effectiveness of neonatal inhalation therapy. AB - Special Care Units are becoming much in demand. However not every hospital can afford them. In this article financial aspects of a specific service for special care, that is inhalation therapy for sick neonates are analyzed. The study is carried out at the Neonatal Intensive Care Unit at the American University of Beirut--Medical Center. Out of 1000 consecutive deliveries, 32 neonates (3.2%) required some form of inhalation therapy. Expenses and entries are computed. Inference is made that this number (1000 deliveries per year) may be sufficient to generate enough entries to cover for expenses to hire specialized personnel. PMID- 3112537 TI - Resource allocation in health care: the allocation of lifestyles to providers. AB - The objective of this article has been to draw the spotlight onto a much neglected facet of the discussion on resource allocation in health care: the process by which society decides what lifestyle the providers of health care may extract, directly or indirectly, from the patient's pocket book. Given the slice of the GNP society surrenders to the providers of health care collectively, the quantity of real health care resources made available to patients obviously varies inversely with the elevation of the lifestyle attained by the providers. These reflections have been triggered by a vexing paradox plaguing contemporary American health care: incessant talk about rationing in the midst of plenty. Conference after conference in this country has been dedicated in recent years to the "agonizing choices visited upon American health care by the age of restricting resources." Remarkably, few of the avid conference organizers, and few of their fiery orators, ever stop to think just what resource flow has actually been constricting. Has it been the supply of physicians? Has it been the supply of hospital beds? Has it been the flow of real purchasing power into the health care system? In general, the preference has been to bypass these questions altogether and to lament in a data-free context. What has been contracting in American health care has not been the flow of money into the sector, nor the flow of professionals, facilities, and entrepreneurs seeking to to do well there by doing good, but, if anything at all, the flow of real health services from providers to patients, certainly to patients who are uninsured and of modest means. And what seems required to solve the sector's problem is not so much an infusion of yet larger sums of money, but a decision-making algorithm capable of using the money already in the system to redirect real health care resources from persons who now receive perilously too many health services to persons who now receive perilously too few. Part of such an algorithm, of course, would be a sensible determination of the lifestyles the health care process needs to support among the providers of care. Under the ideal circumstances envisaged by libertarian thinkers, the determination of these matters could safely be entrusted to the free market. For reasons not difficult to fathom, however, no modern society is willing to adopt that form of arbitration over resource allocation in health care.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3112538 TI - [Use of Broviac and Hickman intra-atrial catheters in children with oncologic diseases and bone marrow aplasia]. PMID- 3112539 TI - Aspirin sensitive asthma and arachidonic acid transformation. AB - Inhibition by nonsteroidal antiinflammatory drugs of cyclooxygenase appears to be the basic mechanism operating in aspirin-sensitive asthma. Evidence in favor of this theory is presented. We also discuss biochemical consequences of blockade of cyclooxygenase for clinical symptomatology, prevention and treatment of aspirin sensitive asthma. PMID- 3112541 TI - Polymer-fume fever associated with cigarette smoking and the use of tetrafluoroethylene--Mississippi. PMID- 3112540 TI - Public Health Service guidelines for counseling and antibody testing to prevent HIV infection and AIDS. PMID- 3112542 TI - Update: acquired immunodeficiency syndrome--United States. PMID- 3112543 TI - FDA workshop on Haemophilus b polysaccharide vaccine--a preliminary report. PMID- 3112544 TI - Premature mortality due to suicide and homicide--United States, 1984. PMID- 3112545 TI - Carbon monoxide poisoning in a garment-manufacturing plant--North Carolina. PMID- 3112546 TI - Pregnant Adolescent Group for Education and Support--Illinois. PMID- 3112547 TI - Imported and indigenous dengue fever--United States, 1986. PMID- 3112548 TI - Meningococcal disease among travelers returning from Saudi Arabia. PMID- 3112549 TI - San Jose Nutrition Education Project--California. PMID- 3112550 TI - Cryptosporidiosis--New Mexico, 1986. PMID- 3112551 TI - Survey of chronic disease activities in state and territorial health agencies. PMID- 3112553 TI - Community oral health surveillance--Columbus, Ohio. PMID- 3112552 TI - Tuberculosis among Hispanics--United States, 1985. PMID- 3112554 TI - Recommendations for prevention of HIV transmission in health-care settings. PMID- 3112555 TI - Immunohistochemical localization and quantitation of NADPH-cytochrome P-450 reductase in human liver. AB - An antibody raised in a goat against the human liver NADPH-cytochrome P-450 reductase (EC 1.6.2.4.) enzyme has been used to: 1) immunoquantify the level of this enzyme in human liver microsomes, and 2) study the distribution of the reductase across the human liver acinus. Employing the Western blot procedure, anti-human reductase IgG recognized a single band in human liver microsomes which corresponded in molecular weight to the purified reductase. The content of the NADPH-cytochrome P-450 reductase in six normal human livers varied from 87 to 121 pmol/mg of microsomal protein. NADPH-cytochrome P-450 reductase activity of the same microsomes ranged from 107 to 222 nmol of cytochrome c reduced per min per mg of protein. The correlation between reductase content and activity (r = 0.54) was not statistically significant (p greater than 0.1). The total cytochrome P 450 content (cytochrome P-450 and P-420) of the same microsomes varied from 423 to 1413 pmol/mg of microsomal protein. The average ratio of cytochrome P-450 to NADPH-cytochrome P-450 reductase was 7.1:1 +/- 3.1 (mean +/- SD) in the human liver microsomal preparations studied. The reductase was found to be nonuniformly distributed across the human liver acinus. Although all hepatocytes stained positively for NADPH-cytochrome P-450 reductase, the staining intensity was highest in zone 3 and in some cases also in zone 1 hepatocytes. These results show that human liver contains a gross excess of cytochrome P-450 molecules to NADPH-cytochrome P-450 reductase molecules. Furthermore, the differential distribution of the reductase within the human liver acinus may lead to a better understanding of the mechanism underlining site-specific drug hepatotoxicity. PMID- 3112556 TI - Calmodulin stimulation of the rat cerebral cortical adenylate cyclase is required for the detection of guanine nucleotide- or hormone-mediated inhibition. AB - Functional interactions between the inhibitory guanine nucleotide-regulatory component (Ni) and the adenylate cyclase catalytic subunit (C) from cerebral cortex have been investigated. The inhibition of adenylate cyclase activity by guanosine 5'-(beta, gamma-imido)triphosphate [Gpp(NH)p] was used as a functional measurement of Ni-C interactions in membranes and cholate extracts. Calmodulin stimulation of C activity was required for the detection of Gpp(NH)p inhibition in these preparations. A similar calmodulin requirement was observed for adenosine receptor-mediated inhibition in membranes. The requirement for calmodulin was demonstrated directly in membranes from which calmodulin had been removed by washing and centrifugation. Adenylate cyclase activity in these preparations was not stimulated by free Ca2+ (1 microM). However, upon the readdition of calmodulin (1 microM), these preparations were stimulated 4-fold by Ca2+. Under these assay conditions, Gpp(NH)p- and adenosine receptor-mediated inhibition was absolutely dependent on Ca2+-calmodulin stimulation. However, forskolin stimulation of activity also restored Gpp(NH)p-mediated inhibition. The following experiments were used to implicate the role of calmodulin in detergent solubilized preparations: (i) by demonstrating that free Ca2+ was required to observe Gpp(NH)p-mediated inhibition, and (ii) by demonstrating that the calmodulin antagonist, calmidazolium, abolished Gpp(NH)p-mediated inhibition while concomitantly decreasing basal activity. As observed in membranes, detection of guanine nucleotide-mediated inhibition required calmodulin stimulation of the detergent-solubilized adenylate cyclase. These results suggest that stimulation of cerebral cortical C activity by either calmodulin or forskolin is required for Ni-mediated inhibition. PMID- 3112557 TI - Muscarinic cholinergic receptors in the embryonic chick heart: interaction of agonist, receptor, and guanine nucleotides studied by an improved assay for direct binding of the muscarinic agonist [3H]cismethyldioxolane. AB - Muscarinic agonist binding has been studied by the indirect method of competition between binding of agonist and 3H-antagonist. Studies of 3H-agonist binding have either been complicated by high levels of nonspecific binding or have been carried out at low concentrations of agonist, which bind only to high affinity sites. A new assay for binding of the muscarinic agonist, [3H]cismethyldioxolane, allows measurement of binding at concentrations up to 1000 nM with a high degree of specificity (92% at 18 nM, 50% at 1000 microM). Using this new binding method, it is possible not only to directly establish the validity of those observations made using competition binding studies, but also to obtain new insight into the mechanism of interaction of receptor agonist and guanine nucleotide. Specifically, data have been presented which demonstrate: 1) that binding of agonist to the high and low affinity forms of the muscarinic receptor involves two independent parallel reactions, and, in the absence of guanine nucleotides, agonist binding alone does not mediate the interconversion of the receptor from one affinity state to another, thus suggesting that high affinity receptors are present in chick heart membranes and do not require agonist binding for their formation; 2) that the interaction of agonist and guanine nucleotide with the receptor-guanine nucleotide-binding protein complex involves formation of an intermediate state in which both agonist and guanine nucleotide are bound to the receptor-guanine nucleotide-binding protein complex; and, finally, 3) that the order of binding of agonist and guanine nucleotide during formation of this intermediate state is random. PMID- 3112558 TI - The role of formate and S-adenosylmethionine in the reversal of nitrous oxide inhibition of formate oxidation in the rat. AB - Studies have been performed in rats in order to test whether methionine reverses the inhibition of formate oxidation produced by nitrous oxide by virtue of the conversion of methionine to formate. At a dose of methionine (100 mg/kg, 671 mumol/kg) that completely reverses the nitrous oxide inhibition of formate oxidation no significant conversion of the methyl group, carboxyl, or backbone of methionine to formate was apparent. No increases in hepatic formate levels were seen after the administration of 671 mumol/kg methionine or ethionine, and formate treatment did not alter the rate of 14CO2 formed after methionine was administered labeled in the methyl, carboxyl, or backbone position. The reversal of nitrous oxide inhibition of formate oxidation was found to correlate temporally with either S-adenosylmethionine levels after methionine administration or S-adenosylethionine levels following ethionine treatment. After methionine or ethionine administration, elevated hepatic steady state levels of tetrahydrofolate were observed and were coincident with elevated S adenosylmethionine or S-adenosylethionine. Since formate oxidation rates are dependent on the hepatic tetrahydrofolate level, the mechanism of methionine reversal of nitrous oxide inhibition appears to be related to effects of hepatic S-adenosylmethionine which are important in maintaining and regulating tetrahydrofolate, rather than formate generation from methionine. PMID- 3112559 TI - Use of a hybrid vaccinia virus-T7 RNA polymerase system for expression of target genes. AB - A novel expression system based on coinfection of cells with two recombinant vaccinia viruses has been developed. One recombinant vaccinia virus contained the bacteriophage T7 RNA polymerase gene under control of a vaccinia virus promoter. The second recombinant vaccinia virus contained a target gene of choice flanked by bacteriophage T7 promoter and termination sequences. Maximum expression of the target gene occurred when cells were infected with 10 PFU of each recombinant virus. Although T7 RNA polymerase synthesis began shortly after infection, the target gene was not expressed until late times and was largely inhibited when DNA replication was blocked. Target gene transcripts were analyzed by agarose gel electrophoresis and had the predicted size. With this system, Escherichia coli beta-galactosidase, hepatitis B virus surface antigen, and human immunodeficiency virus envelope proteins were made. In each case, the level of synthesis was greater than had previously been obtained with the more conventional recombinant vaccinia virus expression system. PMID- 3112560 TI - Rearrangement of rat immunoglobulin E heavy-chain and c-myc genes in the B-cell immunocytoma IR162. AB - Mammalian B-cell lymphoid malignancies frequently display aberrant translocations involving the c-myc proto-oncogene and one of the immunoglobulin loci. We have observed and characterized such a translocation in the immunoglobulin E-producing rat immunocytoma IR162 by using recombinant DNA technology. We show here for the first time that a c-myc gene has recombined with the excluded allele of the nonfunctional epsilon heavy-chain immunoglobulin gene. This recombination has resulted in the loss of 5'-proximal DNA and, consequently, potential regulatory information from the body of the c-myc structural gene via joining to the epsilon heavy-chain switch region in a head-to-head, i.e., 5'-to-5', configuration. As discussed in this report, these results, together with the previous results of others, have important implications for immunoglobulin heavy-chain class switching mechanisms controlling normal and abnormal translocations. PMID- 3112561 TI - Escape from b locus allotype suppression in the rabbit is mediated by IgM molecules bearing an allotope-restricted variant of kappa light chain. AB - Rabbits homozygous for b6 at the kappa light chain b locus were suppressed for the expression of the b6 allotype and then induced to produce auto anti-b6 antibody. Rabbits which subsequently escaped suppression produced auto antibody with restricted allotype specificity. Escape from allotype suppression was mediated by IgM bearing a kappa chain variant with a restricted number of b6 allotopes and having a diminished interaction with auto anti-b6 antibodies from the same and other rabbits escaping b6 suppression. This suggested that there were allelic variants or subpopulations of the b6 light chain which were under independent regulation of expression, clearly influenced by the specificity of auto anti-allotype antibody. Since escape from suppression was mediated by IgM it is proposed that a normal pathway of B cell differentiation occurs during recovery from suppression. PMID- 3112562 TI - A mild method for the preparation of disulfide-linked hybrids of immunoglobulin light chains. AB - A method is described for the hybridization of immunoglobulin light chains (Bence Jones proteins) from different patients. The interchain half-cystine residues in the light chains from one subject are converted into mixed disulfides with 2,2' dithiodipyridine. In the Bence-Jones dimer from a second patient the interchain disulfide bond is reduced with dithiothreitol. A covalently linked hybrid molecule is produced by the reaction of the mixed disulfide with the reduced thiol. In favorable cases the mild treatment yields heterodimers which can be crystallized for X-ray diffraction studies. The procedure can also be employed for converting a monomer into a covalent dimer. The engineered dimer of one kappa chain (Jen) crystallizes in the same space group as an aggregate of monomers, but the unit cell is only one-third as large. PMID- 3112563 TI - [Fatal hepatic failure in a normally developed 5-year-old boy caused by VPA monotherapy]. AB - A five-year-old, normally developed boy who had been healthy except for an absence epilepsy prior to valproate (VPA) treatment died 16 weeks after the introduction of VPA-monotherapy due to liver failure and intractable bleeding disorder. This case emphasizes that the restriction of VPA-therapy to children of more than two years of age, on monotherapy, and without evidence of other diseases or retardation does not exclude fatal complications. Until today world wide about 100 patients have died during VPA-treatment. PMID- 3112564 TI - [Improved method of lipopolysaccharide isolation from gram-negative bacteria]. AB - A modification of the traditional method for lipoplysaccharide isolation from the cells of grammnegative bacteria was elaborated on the basis of extraction by the hot water solution of phenol (the method of Westfahl). To make the method simpler and to raise the yield of the product it was proposed to use the water-phenol extract without its division for plases. The nucleic acids are eliminated by precipitation from dialyzed extract at pH 3,2-3,4 achieved by addition of acetic acid. The comparative isolation of lipopolysaccharides by the classic and modified methods has confirmed the advantages of a new technique. PMID- 3112566 TI - Comparative mutagenicity of 3-azido-1,2-propanediol and sodium azide in various pro- and eu-karyote systems. PMID- 3112565 TI - The formation of reactive intermediate(s) of glucose 6-phosphate and lysine capable of rapidly reacting with DNA. AB - Glucose has been shown to react nonenzymatically in vitro with DNA, to form products with spectral properties similar to those observed with the nonenzymatic glycosylation of proteins in vivo. The incubation in vitro of glucose or glucose 6-phosphate with f1 phage DNA results in a time- and concentration-dependent loss of transfection efficiency. It has also been shown that incubation in vitro of pBR322 DNA with glucose 6-phosphate prompts a loss in transformation capability as well as gross DNA alterations. In the present communication, we have investigated a model reaction of glucose 6-phosphate with the amino groups of lysine to form reactive intermediates which are capable of forming covalent adducts with DNA. The preincubation of glucose 6-phosphate and [3H]lysine leads to a time- and concentration-dependent formation of reactive intermediates. These intermediates, which accumulate with time, can subsequently react with single- or double-stranded DNA to form acid-stable complexes. Studies done with synthetic polynucleotides suggest low reactivity of the intermediate with thymidine. The formation of the reactive intermediates is saturated by the addition of excess unlabeled lysine. Once formed the intermediates are insensitive to the addition of aminoguanidine and to reduction by sodium borohydride. The chemical reactions between sugars and lysine reported here and the reactivity of that product with DNA provide a model for exploring the classes of DNA damage that may contribute to the loss of DNA function during aging. PMID- 3112567 TI - Mutagen detection with a mouse line containing 3 distinct mutations conferring sensitivity. AB - A mouse-cell mutant sensitive to methyl methanesulfonate (MMS), X-rays, ultraviolet light (UV), and crosslinking agents was selected using the replica plating and cell suspension spotting methods. This mutant (XUM1) is a mitomycin C sensitive derivative of previously reported XU1, a mutant sensitive to MMS, X rays and UV. Since XU1 is highly susceptible to the lethal effect of 4 nitroquinoline-1-oxide (4NQO), XUM1 is also hypersensitive to 4NQO. Growth inhibition area tests showed that low concentrations of mutagens were detected with the multiple mutagen-sensitive mutant XUM1. Hence XUM1 cells will be useful in detecting with high sensitivity a wide range of mutagens and carcinogens which mimic X-rays, UV and crosslinking agents. PMID- 3112569 TI - Pain control. PMID- 3112568 TI - Effect of fagaronine on chromosome breaks and loss in Drosophila melanogaster. AB - Fagaronine, a potent antileukemic agent, was shown to induce chromosome breaks and loss in sperm of Drosophila melanogaster. PMID- 3112570 TI - Effect of spinal cord TRH deficiency on lower motorneuron function in the rat. AB - Thyrotropin-releasing hormone (TRH), present in high concentrations in the mammalian spinal cord, exerts excitatory effects on the alpha-motorneuron (AMN) via axodendritic contacts. We used the neurotoxin 5,7-dihydroxytryptamine (5,7 DHT) to deplete TRH from the ventral horn of the spinal cord of adult rats to determine whether the tripeptide may be trophic to the AMN. The rats were studied blindly and sequentially for 11 weeks. Motor performance remained normal by clinical and electrophysiologic assessments. AMN counts were not reduced in the lumbar cord, and gastrocnemius muscle showed no evidence of denervation in treated rats. We conclude that in the adult rat chronic ventral horn TRH deficiency does not lead to AMN degeneration and is not associated with a significant alteration of AMN function. PMID- 3112571 TI - Increased serum myosin light chain 3 level in neuromuscular diseases. AB - A radioimmunoassay for human skeletal muscle myosin light chain 3 (MLC-3) was developed. The serum level of MLC-3 was evaluated in 143 patients suffering from neuromuscular diseases. Increased MLC-3 level was observed in muscular dystrophies. There were significant positive correlations between serum levels of MLC-3 and creatine kinase (CK) in Duchenne and limb-girdle type muscular dystrophy, but the regression lines were different. Patients with neurogenic amyotrophy, especially amyotrophic lateral sclerosis, also showed elevated MLC-3 levels with or without high CK, and the frequency of increase in MLC-3 was greater than that of CK. The results of the present study suggest that circulating MLC might be a useful marker for muscle breakdown not merely in myopathies but in neurogenic disorders. PMID- 3112572 TI - Detection of adenosine diphosphate-ribosyl transferase activity in the filarial worm, Onchocerca volvulus. AB - The existence of the nuclear enzyme ADP-ribosyl transferase in the filarial worm Onchocerca volvulus was demonstrated. The enzyme activity was observed in the nuclear preparation from the parasitic organism. Poly(ADP-ribose) was identified as the reaction product by the isolation of phosphoribosyl-AMP and 5'AMP as the major products of snake-venom phosphodiesterase digestion. The temperature and pH optima for the enzyme were 25 degrees C and 8.5, respectively. The apparent Km value exhibited by the substrate NAD+, is 750 microM and the activity of the enzyme is inhibited by four chemical classes of inhibitors, nicotinamides, methylxanthines, thymidine and aromatic amides. PMID- 3112573 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 36-1987. A 14-year-old girl with diabetic ketoacidosis and pneumonitis with cavitation. PMID- 3112574 TI - Proteolytic activity of lactic acid bacteria in skim milk with special reference to the biodegradation of casein fractions. AB - Streptococci and lactobacilli were assayed for their proteolytic activity in pasteurised (95 degrees C for 30 min) fresh Friesian cows' skim milk incubated at 30 degrees C for 48 h. Lactobacilli were more proteolytic than the streptococci except S. faecalis subsp. liquefaciens. S. faecalis and S. thermophilus followed S. lactis subsp. diacetylactis in the proteolytic activity. Electrophoretic analysis of the precipitated casein revealed K-, pre-beta- and the small slow band of alpha s1-casein to be the most fractions and beta-casein the least fraction susceptible to the biodegradation. S. faecalis subsp. liquefaciens was the only organism able to degrade beta-casein to 3 fractions within 48 h. S. lactis with its subsp. diacetylactis was characterized by its inability to degrade gamma-casein. Addition of 2.0 g glucose, 0.5 g yeast extract, 2.0 mmol Mg2+, 0.5 mmol Mn2+ and 0.1 mmol Fe2+/l of skim milk culture of each L. casei and L. plantarum increased acid formation but decreased proteolysis. 6% NaCl was inhibitory to both. After 60 days at 18 degrees C, a fraction, probably derived from beta-casein, was noticeable. The large intense band of alpha s1-casein appears to be degraded gradually to only small peptides which in turn are transferred immediately into the cells. The hydrolysis of gamma-casein and beta casein also appears to be inhibited by exogenously supplied NaCl and nutrients, respectively. PMID- 3112575 TI - Proteolytic activity of crude cell-free extract of Lactobacillus casei and Lactobacillus plantarum. AB - Crude cell-free extracts of some strains of each L. casei and L. plantarum were assayed for their amino-, imino- and endopeptidase as well as the caseinolytic activity. L-alanine-, L-phenylalanine- and L-leucine-p-nitroanilide but not L glutamic acid-p-nitroanilide, were hydrolyzed by all the strains indicating an amino-peptidase activity. The activity of proline iminopeptidase was very low compared to that of the aminopeptidase. L. casei could be distinguished from L. plantarum by its high endopeptidase activity against succinyl-phenylalanine- and glutaryl-phenylalanine-p-nitroanilide. The caseinolytic activity of cell-free extract of L. casei ATCC 393 was about one seventh the caseinolytic activity of intact cells, suggesting that the bulk of the cellular proteinase activity is located in the cell wall. It appears that a metallo aminopeptidase and a probable cysteine one are involved in the hydrolysis of amino acid-p-nitroanilide, whereas the endopeptidase activity appears to be related to a cysteine enzyme. Incubation of gels with L-leucine-p-nitroanilide after electrophoresis allowed the revealing of 2 zones of aminopeptidase activity in a strain of L. casei and only one in two others, but in L. plantarum it did not allow the revealing of any. The high proteolytic activities of L. casei compared to those of L. plantarum may explain its more frequent occurrence in cheese and its probable role in the ripening of many cheese varieties. PMID- 3112576 TI - [Communication as a scientific method--an experience in interactions with monkeys]. PMID- 3112577 TI - Genentech loses another patent dispute in court. PMID- 3112578 TI - Proteins as molecular chaperones. PMID- 3112580 TI - Differential polarization microscopy of changes in structure in spermatocyte nuclei. AB - Phase-dependent forms of microscopy (such as phase contrast, interference, or polarization microscopy) have been used for many years; the amount of phase retardation produces images based mainly on index of refraction. We have developed a microscope that forms images that depend on small differences in extinction for different forms of incident polarized light. By modulating the polarization of light incident on the sample and digitally recording the difference in intensities of transmitted light, we obtain images which specifically reveal either ordered linear structures or chiral (right- or left handed) structures. Linearly polarized light, incident alternately with two perpendicular directions of polarization, forms images of structures which have linear order or linear orientation. Right-handed and left-handed circularly polarized light incident alternately on a sample forms images of chiral structures. Structures with neither linear order nor chirality are essentially invisible. Thus, images based on linear dichroism, circular dichroism, and linear and circular differential scattering can be used to detect specific types of structures which may be difficult to observe by conventional methods. We have used such 'linear and circular differential imaging' to study the structure of the nucleolus (the site of RNA synthesis) in live primary spermatocytes of Drosophila when they are transcriptionally active or inactive. Some inactive nucleoli are bipartite, with two distinct structures visible by differential scattering of both linearly and circularly polarized light. The active nucleolus is a single domain; it is clearly distinguished from part of the Y chromosome, and it shows different internal structure with linearly and circularly polarized light. Thus, polarization-dependent images reveal structures which can be associated with the transcriptional activity of cells. PMID- 3112579 TI - Two zinc fingers of a yeast regulatory protein shown by genetic evidence to be essential for its function. AB - The best-understood protein structure involved in DNA binding is the helix-turn helix motif. A second DNA-binding domain, the finger structure, has been proposed on the basis of sequence analysis, partial proteolysis and zinc content of Xenopus transcription factor TFIIIA. Other eukaryotic proteins were subsequently found to contain contiguous repeat units of the postulated finger motif. Each repeat unit contains thirty amino acids and is thought to bind a zinc atom using two cysteines and two histidines as ligands. The protein loop or finger between apparent zinc ligands is rich in DNA-binding residues and is thought to make specific contacts with DNA. The yeast protein ADR1, a positive regulator of transcription of the gene ADH2, contains two finger domains in a region of the protein required for transcriptional activation. Nineteen independently isolated adr1 mutations induced by hydroxylamine were found at nine different amino-acid positions, seven of which are in the two finger domains. All four mutations that altered invariant cysteine or histidine residues led to an adr1 null phenotype. Only one other mutation caused an adr1 null phenotype. Thus, one finger domain is not sufficient for ADR1 activity. This provides the first evidence that, as is consistent with the proposed model, the invariant cysteine and histidine residues are essential for the formation of the finger structure. PMID- 3112581 TI - Mechanism of insulin action. PMID- 3112582 TI - Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen. AB - Mature T cells segregate phenotypically into one of two classes: those that express the surface glycoprotein CD4, and those that express the glycoprotein CD8. The CD4 molecule is expressed primarily on helper T cells whereas CD8 is found on cytotoxic and suppressor cells. A more stringent association exists, however, between these T-cell subsets and the major histocompatibility complex (MHC) gene products recognized by their T-cell receptors (TCRs). CD8+ lymphocytes interact with targets expressing class I MHC gene products, whereas CD4+ cells interact with class II MHC-bearing targets. To explain this association, it has been proposed that these 'accessory' molecules bind to monomorphic regions of the MHC proteins on the target cell, CD4 to class II and CD8 to class I products. This binding could hold the T cell and its target together, thus improving the probability of the formation of the trimolecular antigen: MHC: TCR complex. Because the TCR on CD4+ cells binds antigen in association with class II MHC, it has been difficult to design experiments to detect the association of CD4 with a class II molecule. To address this issue, we devised a xenogeneic system in which human CD4 complementary DNA was transfected into the murine CD4-, CD8- T-cell hybridoma 3DT-52.5.8, the TCR of which recognizes the murine class I molecule H 2Dd. The murine H-2Dd-bearing target cell line, P815, was cotransfected with human class II HLA-DR alpha, beta and invariant chain cDNAs. Co-culture of the parental T-cell and P815 lines, or of one parental and one transfected line resulted in a low baseline response. In contrast, a substantial increase in response was observed when CD4+ 3DT-52.5.8 cells were co-cultured with HLA-DR+ P815 cells. This result strongly indicates that CD4:HLA-DR binding occurs in this system and that this interaction augments T-cell activation. PMID- 3112583 TI - Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. AB - It has been suggested that the proto-oncogenes c-fos and c-myc participate in the control of genetic events which lead to the establishment of prolonged functional changes in neurons. Expression of c-fos and c-myc are among the earliest genetic events induced in cultured fibroblast and phaeochromocytoma cell lines by various stimuli including growth factors, peptides and the intracellular second messengers diacylglycerol, cAMP and Ca2+. We report here that physiological stimulation of rat primary sensory neurons causes the expression of c-fos-protein like immunoreactivity in nuclei of postsynaptic neurons of the dorsal horn of the spinal cord. Activation of small-diameter cutaneous sensory afferents by noxious heat or chemical stimuli results in the rapid appearance of c-fos-protein-like immunoreactivity in the superficial layers of the dorsal horn. However, activation of low-threshold cutaneous afferents results in fewer labelled cells with a different laminar distribution. No c-fos induction was seen in the dorsal root ganglia, gracile nucleus or ventral horn. Thus, synaptic transmission may induce rapid changes in gene expression in certain postsynaptic neurons. PMID- 3112584 TI - The ras gene. Transformer and transducer. PMID- 3112585 TI - Cytoskeleton: protean proteins perceived. PMID- 3112586 TI - Maturational patterns in early hominids. PMID- 3112587 TI - Disguise of antibiotics. PMID- 3112589 TI - Selective endoscopic treatment of bronchogenic carcinoma with the carbon dioxide surgical laser. An uncommon new indication for laser bronchoscopy. PMID- 3112588 TI - Modification of GABA turnover in the striatum and hippocampus of the rat after zopiclone. AB - The effects of zopiclone, a non-benzodiazepine compound that interacts with benzodiazepine receptors, on GABA turnover rate and GABA content in the rat striatum and hippocampus have been studied. Intraperitoneal administration of zopiclone reduced the GABA turnover rates in both the striatum and hippocampus, as estimated from the rate of GABA accumulation after inhibition of GABA transaminase by aminooxyacetic acid (AOAA). The effect of zopiclone on AOAA induced accumulation of GABA in the hippocampus and striatum was blocked by the intraperitoneal injection of the benzodiazepine receptor antagonist Ro 15-3505. Furthermore, zopiclone slightly but significantly decreased GABA content in the hippocampus, the decrease being blocked by coadministration of the benzodiazepine receptor antagonist Ro 15-1788. Our results confirm that the GABAergic system plays a role in the mechanism of action of zopiclone. PMID- 3112590 TI - [Promoting lactation with the aid of drugs]. PMID- 3112591 TI - [Free fibula transplantation with restoration of the blood supply]. PMID- 3112592 TI - [Immunization of travelers to (sub)tropical areas]. PMID- 3112593 TI - Stage IIb, IIIb, and IVa carcinoma of the uterine cervix--results of treatment by radiotherapy in 649 patients. AB - During the period of January 1969 to December 1980, 649 patients have been treated by radical radiotherapy for Stage IIb, IIIb, and IVa carcinoma of the cervix uteri. This retrospective study was performed to assess therapeutical results in two groups of patients. Clinical staging and the methods of treatment were standard in both groups. Group I was treated by external irradiation of the pelvis minor with 60Co in combination with intracavitary radium administration. Group II patients were irradiated with a 42 MeV betatron according to the findings of lymphography, again in combination with radium brachytherapy. In Group I the 5-year survival rate was 59.2%, that in Group II was 66.7%. There was a statistically significant difference in the 5-year survival rate in Stage IIb patients of Group II (85.5%) against that in Group I (75.6%). The incidence of serious complications elicited by radiotherapy increased from 4.8% in Group I patients to 7.5% in Group II. Clinical stage, age at the time of diagnosis, findings of lymphography and tolerance to irradiation are prognostically important factors that influence the cure of the patients. On the basis of these findings, the possibilities of further therapeutic improvements are discussed. PMID- 3112594 TI - [Monitoring sodium valproate treatment of epilepsy in the development years]. AB - The levels of sodium valproate were determined in the blood and saliva of children treated for epilepsy. The determination of drug in saliva may be a simple test checking whether the patient is taking the drugs systematically, and makes possible determination of the approximate level in the serum without blood sampling. In doubtful cases poorly responding to treatment serial monitoring of valproic acid should be undertaken. PMID- 3112595 TI - [Ito's hypomelanosis--a neurocutaneous syndrome]. AB - The authors describe the clinical manifestations of the little known neurodermal syndrome described in 1952 by Ito and called Ito's hypomelanosis. Two own cases are presented. PMID- 3112596 TI - A unifying concept on the pathogenesis of brain oedemas. AB - The molecular mechanisms operating within the cerebral endothelium have been analysed in relation to the formation of brain oedema states. With respect to their pathogenesis, the activation of a cyclic nucleotide-generating system and lipolysis seems in particular to be of neuropathological importance. As these molecular mechanisms were seen to be activated in oedemas with primary vascular reactions and in those following ischaemic brain injury, it is proposed that, from a pathogenetic point of view, brain oedemas have a common vascular origin. PMID- 3112597 TI - Growth hormone responses in isolated protein deficiency state in rhesus monkey. AB - We have longitudinally studied the effects of protein-deficient diet on serum growth hormone (GH) concentration in rhesus monkey. A biphasic basal GH response and a phenomenon of failure to suppress GH levels after glucose administration were observed in animals fed diet lacking proteins. GH levels remained consistently elevated in protein-deprived monkeys. Whether these elevations in GH will have any deleterious influence on the host remains to be seen. PMID- 3112598 TI - Permissive role for ornithine decarboxylase and putrescine in the luteinising hormone surge. AB - Anterior pituitary gland fragments removed from Wistar-derived rats at 10.00 h on pro-oestrus were perifused with Krebs-bicarbonate medium in a column and exposed to hourly volleys of 6 1-min pulses of 10 nM luteinising hormone (LH)-releasing hormone (LHRH). LH release showed a characteristic pattern of prolonged (over 5 h) sensitisation to the releasing hormone, with the response to each volley becoming progressively greater. The addition of 2 mM difluoromethylornithine (DFMO; an inhibitor of ornithine decarboxylase) to the perifusion medium completely inhibited the response to all volleys of LHRH. This effect of DFMO was reversed by the concurrent inclusion of 2 mM putrescine in the medium. Putrescine alone had a small but non-significant enhancing effect on LHRH-induced release, and no significant effect on basal LH release in this system. In a second series of experiments, tissues were loaded with 1-14C-ornithine and the radioactive carbon dioxide released into the medium during the perifusion monitored. Unstimulated pituitary tissues showed constant low levels of carbon dioxide release during 5 h of incubation, but those given hourly volleys of LHRH showed progressively increasing release of radioactivity, which was blocked by the addition of DFMO. No LHRH-stimulated increase in 14CO2 production from 1-14C ornithine was seen from pituitary tissue removed at 10.00 h on dioestrus. Administration of DFMO (10-100 mg/rat) on the afternoon of pro-oestrus 4 h before the expected peak of the LH surge reduced the magnitude of the subsequent surge and the concentration of the hormone found in the anterior pituitary gland in a dose-related manner. In addition, the concentration of putrescine, but not of spermidine or spermine, was significantly reduced in treated animals (50 mg/rat) at the time of this attenuated surge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112599 TI - Inhibition of hypothalamic gonadotropin-releasing hormone release by endogenous opioid peptides in the female rabbit. AB - Recent evidence suggests that the endogenous opioid peptides (EOPs) inhibit luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by suppression of hypothalamic gonadotropin-releasing hormone (GnRH) release, and that the feedback inhibition by EOPs is influenced by ovarian steroids. In the present studies, intact (INT) and ovariectomized (OVX) adult female rabbits were fitted with femoral vein catheters and mediobasal hypothalamic (MBH) push-pull perfusion (PPP) cannulae. One week after brain cannulation, does were subjected to 6 h of PPP and sequential blood sampling. In experiment I, INT (n = 6) and OVX (n = 5) does were infused intravenously with saline for 4 h followed by 2 h of infusion of the opiate antagonist naloxone (NAL; 10 micrograms/min/kg) while the MBH was simultaneously perfused with media. In experiment II, INT (n = 5) and OVX (n = 5) does were perfused with media for 4 h followed by 2 h of intrahypothalamic (IHP) NAL perfusion (0.2 microgram/min). The GnRH in push-pull perfusates and LH and FSH in plasma samples collected at 10-min intervals were measured by specific radioimmunoassays. In INT does, neither intravenous infusion nor IHP perfusion of NAL altered pulsatile parameters of GnRH or LH release. In contrast, both intravenous and IHP NAL administration stimulated GnRH and LH release within 30 50 min in OVX does by marked increases in both GnRH and LH pulse amplitudes. Neither route of NAL administration affected FSH secretion in any of the treatment groups. We conclude that EOPs are involved in the inhibition of hypothalamic GnRH secretion in OVX does; the feedback inhibition by ovarian steroids on the hypothalamic-pituitary axis in the rabbit is sufficient to compromise the effects of EOPs, and under these experimental conditions, the hypothalamic mechanisms which regulate the secretion of pituitary LH and FSH may be independent. PMID- 3112600 TI - The secretory activity of the tuberoinfundibular dopaminergic neurons is modulated by the thyroid status in the adult rat: consequence on prolactin secretion. AB - An influence of thyroid status on the secretory activity of hypothalamic dopaminergic neurons was observed in adult rats and its involvement in the regulation of prolactin (PRL) secretion was examined. The secretory activity of the tuberoinfundibular dopaminergic (TIDA) neurons was evaluated by measurement of dopamine (DA) biosynthesis in the neurons and DA release into hypophysial portal blood. The accumulation of DA and PRL in the adenohypophysis as well as PRL concentration in plasma were also estimated, and the various parameters were studied in thyroidectomized (TX), sham TX, TX rats treated for 7 days with thyroxine (T4; 20 micrograms/kg body weight daily) as well as in intact rats treated similarly with T4. An enhanced secretory activity of the TIDA neurons was observed in TX compared to sham TX rats, as attested by an increased synthesis of DA in the neurons, a greater concentration of DA in hypophysial portal plasma as well as an augmented accumulation of DA in the adenohypophysis. In the same animals, PRL was reduced in the adenohypophysis and in plasma, reflecting a blunted secretion of PRL in severe hypothyroidism. Treatment of TX rats with T4 for 7 days abolished all effects observed in TX rats, DA synthesis in TIDA neurons of TX rats treated with T4 being even less than in neurons of sham TX animals. A similar treatment with T4 administered to intact rats did not affect the secretory activity of the TIDA neurons nor the secretion of PRL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112601 TI - Cerebral circulation during arteriovenous malformation operation. AB - The circulatory changes in the cortex around a cerebral arteriovenous malformation (AVM) were studied in 18 patients. The AVMs had rapid circulation times with early draining veins on angiography. Local cortical blood flow (lCoBF) was measured with cortically applied thermister/Peltier stack arrays. The AVMs had a more pronounced effect on lCoBF at a 2- to 4-cm distance from the AVM margin than in the adjacent cortex. Mean preexcision lCoBF was 62.9 +/- 6.7 (SE) ml/100 g/minute (i.e., similar to normal controls) near the AVM margin and 43.0 +/- 4.2 ml/100 g/minute far (i.e., greater than 2 cm) from the AVM. CO2 reactivity (COR) before excision was 1.1 +/- 0.3 ml/100 g/minute/torr of CO2 (i.e., similar to normal controls) at near sites and 0.6 +/- 0.3 ml/100 g/minute/torr of CO2 at far sites. The mean postexcision near lCoBF remained stable at 55.8 +/- 5.1 ml/100 g/minute at near sites, but the far lCoBF significantly increased (P less than 0.05) to 57.2 +/- 6.8 ml/100 g/minute. The cortical feeding artery pressure was substantially below the normal cortical artery pressure in 50% of the cases studied. Pressure in these arteries normalized after occlusion and AVM excision, resulting in a rapid increase in cortical artery perfusion pressure. Draining red vein pressure, which was elevated before AVM excision, also dropped after excision, contributing to the increase in perfusion pressure. Two patients who developed the normal perfusion pressure breakthrough syndrome (PBS) after operation had low lCoBF and disturbed COR before AVM excision and marked increase of lCoBF after excision.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112603 TI - Segmental neurofibromatosis. AB - Of the various forms of neurofibromatosis, the best known are peripheral neurofibromatosis (von Recklinghausen's disease) and central neurofibromatosis. There is a rare form called segmental neurofibromatosis, in which the cutaneous and neural changes are limited to one sector of the body and with which there is usually no family history of neurofibromatosis. We report four patients with this disorder and stress the value of repetitive, limited excision of peripheral nerve tumors in their management. PMID- 3112602 TI - Increased delivery of tumor-specific monoclonal antibodies to brain after osmotic blood-brain barrier modification in patients with melanoma metastatic to the central nervous system. AB - We evaluated the delivery of melanoma-specific radiolabeled monoclonal antibody (MAb) Fab fragments in a pilot study of three patients with melanoma metastatic to the central nervous system. Tumor samples demonstrated excellent immunohistochemical reactivity with Fab 96.5, specific for a 97,000-molecular weight melanoma antigen (p97), or Fab 48.7, specific for a melanoma-associated proteoglycan antigen. All three patients received 131I-labeled tumor-specific Fab (5 to 7 mg, 1 mCi/mg) intravenously. On a separate occasion, two patients received 131I-labeled nonspecific Fab (5 to 7 mg, 1 mCi/mg). There was no uptake of either antibody into the region of the tumor (as documented by gamma camera brain images). However, there was increased uptake in the blood-brain barrier (BBB)-modified areas in all three patients when radiolabeled tumor-specific MAb was administered intravenously in conjunction with osmotic BBB opening. In one patient, the estimated cerebrovascular permeability X capillary surface area (PA) for the tumor-bearing hemisphere 3 hours after disruption was 1.16 X 10(-6) sec-1 compared to the PA of 0.395 X 10(-6) sec-1 in the nondisrupted hemisphere. Serial brain scans showed that greater than 90% of the radiolabeled antibody cleared from the brain by 72 hours. The highest radiation doses (rads) calculated per 7 mCi injection were: left brain (barrier-modified hemisphere), 5.46; right brain (non-barrier modified hemisphere), 1.68; thyroid, 98; stomach, 9.1; kidney, 39.9; and total body, 1.33. There seemed to be increased uptake of antibody in the tumor region after barrier modification in one patient, but antibody clearance from that region occurred at the same rate as from surrounding and apparently tumor-free brain. In one patient who had carcinomatous meningitis, we demonstrated antibody bound to only a fraction of the antigen binding sites on tumor cells in the cerebrospinal fluid after BBB modification. We have not shown distinct, persistent localization of antibody in brain tumor; studies investigating MAb dose and other parameters as the basis for this problem are under way. PMID- 3112604 TI - In vitro effects of ionophores and inhibitors of main sodium and calcium movements on tyrosine and tryptophan transport by human erythrocytes. AB - Peripheral models using blood cells might be biochemical markers in various psychiatric illnesses. In previous papers we reported a deficit of tyrosine and tryptophan transport in red cells incubated in plasma from depressed patients. In the present study we investigated the role played by sodium and calcium in these transports by using inhibitors and ionophores of the main movements of these electrolytes. We also studied the contribution of phloretin-sensitive countertransport, which has been described as low in psychiatric conditions. PMID- 3112605 TI - Cavernous sinus subarachnoid diverticulum and sixth nerve palsy. AB - Metrizamide CT cisternography in a young woman with a chronic sixth nerve palsy demonstrated a cavernous sinus subarachnoid diverticulum originating from the cerebellopontine cistern. The possible etiologic role of this diverticulum in her palsy is discussed. PMID- 3112606 TI - Further studies on ectopic dendrite growth and other geometrical distortions of neurons in feline GM1 gangliosidosis. AB - Systematic Golgi studies have been performed on major subcortical, diencephalic, brain stem and spinal cord regions from cats with the inherited neuronal storage disease, GM1 gangliosidosis. Resulting data have been compared with other Golgi studies of neuronal storage disorders in man and animals, including an earlier, more limited examination of this same disease model. These previous studies have shown that in human and feline gangliosidoses cortical pyramidal neurons undergo remarkable changes in soma-dendritic geometry. The latter include the formation of conspicuous cellular enlargements between somata and axonal initial segments (meganeurites) and the sprouting of secondary neuritic processes from this same region of the cell. Further, ultrastructural studies have revealed normal appearing synapses on the surface of this ectopically placed dendritic-like membrane. Results of the present study indicate that the distribution of meganeurites, secondary neurites and other geometrical distortions of neurons in GM1 gangliosidosis varies with cell type and brain region. This cell type specific response to the metabolic error and subsequent storage could be categorized in three ways. Firstly, certain types of cells (e.g. multipolar neurons of the amygdala and claustrum) exhibited changes similar to those reported for cortical pyramidal neurons. That is, cells of these regions either displayed spine or neurite-bearing meganeurites, or enlarged axon hillocks which were covered with similar processes. Other types of neurons did not demonstrate ectopic neurite growth or spine-covered meganeurites, but did display prominent aspiny meganeurites (e.g. neurons of the superior colliculus, periaqueductal gray, hypothalamus and basal forebrain nuclei). A third category of neurons did not possess meganeurites or neurite growth but instead demonstrated massive somatic expansion which exceeded that observed in meganeurite-bearing cell types (e.g. certain brain stem and spinal cord neurons). These data have been compared with the more limited Golgi studies of other types of neuronal storage disorders and the same types of neurons appeared to respond in similar fashion across this spectrum of diseases. The data presented and discussed in this paper demonstrate three significant morphological events which occur in neurons as a result of lysosomal hydrolase deficiency. These are storage, which occurs in all neurons but manifests as meganeurite formation or somatic enlargement depending on the cell type, axon hillock or meganeurite-associated spine and neurite growth, and new synapse formation on spine-covered meganeurites and on neurites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112608 TI - Risk factors for absence seizures: a population-based case-control study in Rochester, Minnesota. AB - To our knowledge, this is the first population-based case-control study of risk factors for absence seizures (AS). Diagnosis of AS was based on clinical criteria. The complete medical history of potential cases, available through the records-linkage system for residents of Rochester, MN, was independently reviewed by three neurologists who agreed upon the diagnosis. All AS patients who were residents of Rochester at time of diagnosis between 1935 and 1979, and who were born in this community, were included (N = 30). Two population controls (born in Rochester) were matched to each patient, and for both patients and controls, the records-linkage system was used to obtain information about possible risk factors. The only factor significantly more common in cases than in controls was a history of febrile seizures (odds ratio = 12; p less than 0.01). We suggest that these febrile seizures represent either an early manifestation of the convulsive diathesis or the symptom of a preexisting brain dysfunction. None of the other factors investigated reached statistical significance, including those that have been previously suggested such as twin pregnancy, breech presentation at delivery, being first-born, and perinatal asphyxia. Sample size limitations should be considered in interpreting these findings. PMID- 3112607 TI - Changes in the localization of brain prion proteins during scrapie infection. AB - Prion proteins (PrP) were localized in the brains of normal and scrapie-infected hamsters by immunohistochemistry and Western blotting. PrP monoclonal antibodies and monospecific anti-PrP peptide sera, which react with both the cellular (PrPC) and scrapie (PrPSc) isoforms of the prion protein, were used to locate PrP in tissue sections. In normal hamsters, PrPC was located primarily in nerve cell bodies throughout the CNS; whereas, in the terminal stages of scrapie, PrP immunoreactivity was shifted to the neuropil and was absent from most nerve cell bodies. Prion proteins were not uniformly dispersed throughout the gray matter of scrapie-infected hamster brains; rather, they were concentrated in those regions that exhibited spongiform degeneration and reactive astrogliosis. Since earlier studies showed that the level of PrPC remains constant during scrapie infection as measured in whole brain homogenates and no antibodies are presently available that can distinguish PrPC from PrPSc, we analyzed individual brain regions by Western blotting. Analysis of proteinase K-digested homogenates of dissected brain regions showed that most of the regional changes in PrP immunoreactivity that are seen during scrapie infection are due to the accumulation of PrPSc. These observations indicate that the tissue pathology of scrapie can be directly correlated with the accumulation of PrPSc in the neuropil, and they suggest that the synthesis and distribution of the prion protein has a central role in the pathogenesis of this disorder. PMID- 3112609 TI - Antifilamin, antivinculin, and antitropomyosin antibodies in myasthenia gravis. AB - Antifilamin, antivinculin, and antitropomyosin antibody activities were investigated in sera from 43 patients with myasthenia gravis (MG). Antifilamin and antivinculin antibody activities are significantly higher in MG patients compared with normal controls and patients with Duchenne muscular dystrophy (DMD), Parkinson's disease, and spinocerebellar degeneration. The antifilamin antibody was highly positive (100%) in ocular myasthenia. Antitropomyosin antibody activity was similar to that in DMD patients. No correlation was observed between these antibody activities and the antiacetylcholine receptor antibody titers, the duration of the disease, and thymic pathology. PMID- 3112610 TI - Free light chains in multiple sclerosis and infections of the CNS. AB - The intrathecal humoral immune response was analyzed in 83 patients with MS and 35 patients with acute CNS infections. CSF free kappa chains and CSF free lambda chains were quantified by radioimmunoassay; CSF IgG and albumin were measured by electroimmunodiffusion. The MS patients were characterized by higher levels of free kappa chains; free kappa:free lambda chain ratio; free kappa chain:albumin ratio; and IgG:albumin ratio. There were no differences in the level of free lambda chains or absolute concentration of IgG. A significant correlation was observed between free kappa chains and total IgG in MS and between free lambda chains and total IgG in infections, suggesting that the immune response was predominantly IgG-kappa in MS and IgG-lambda in infections. PMID- 3112611 TI - Clinical valproate toxicity induced by acetylsalicylic acid. AB - We report three patients with serious clinical valproate (VPA) toxicity induced by interaction with acetylsalicylic acid (ASA). Two patients had a documented rise in VPA free level, and the third showed only clinical signs of toxicity. Symptoms resolved in all three when the ASA was stopped. This interaction has been previously documented under experimental conditions, and is due to displacement of VPA from plasma protein binding sites and a probable interference in metabolism. This is the first report of the clinical significance of this interaction. PMID- 3112612 TI - Case for diagnosis. AIDS. PMID- 3112613 TI - Safe practice for our aeromedical evacuation patients. PMID- 3112614 TI - Naval Support Activity Hospital Da Nang combat casualty deaths January to June 1968. PMID- 3112615 TI - Health and fitness profiles of male military officers. PMID- 3112616 TI - Complications of a medical unit, self-contained transportable operating room adapted to fixed facility standards in the continental United States--the first 200 cases. PMID- 3112617 TI - Combat Lifesaver training: medical training for the non-medic. PMID- 3112618 TI - Exercise as a treatment option for anxiety and depressive disorders. PMID- 3112619 TI - The military as a provider of public health services after a disaster. PMID- 3112620 TI - Medical functioning and circadian dysrhythmia. PMID- 3112621 TI - The incidence, assessment, and management of pressure sores in orthopaedic patients. PMID- 3112623 TI - An immunohistologic study of a splenic cyst. PMID- 3112622 TI - Detection of intra-abdominal hematomas using intraperitoneal xenon 133. PMID- 3112624 TI - Electronic fetal monitoring in face presentation at term. PMID- 3112625 TI - Lung cancer in young patients: a ten-year experience at William Beaumont Army Medical Center. PMID- 3112627 TI - Non-adaptability to basic training and the Millon Clinical Multiaxial Inventory. PMID- 3112626 TI - Eosinophilic granuloma of frontal bone. PMID- 3112628 TI - Organ procurement and the Armed Forces--a personal perspective. PMID- 3112629 TI - Auguste Charles Valadier: a pioneer in maxillofacial surgery. PMID- 3112630 TI - Paramedical consultations: the role of nonphysician health care providers in the care of hospitalized patients. PMID- 3112631 TI - Descriptive epidemiology of an outbreak of hepatitis B in the U.S. Army, Europe. PMID- 3112632 TI - Aviation clinical psychology. PMID- 3112633 TI - Army Expert Field Medical Badge (EFMB) enhances Air Force medical readiness. PMID- 3112634 TI - Management Support System: automation of patient appointments in the U.S. Army. PMID- 3112635 TI - Little arrows. PMID- 3112636 TI - The management of purified protein derivative convertors in the Fleet Marine Force. PMID- 3112637 TI - Endometriosis of the vermiform appendix. PMID- 3112638 TI - Resolution of epidermolysis bullosa aquisita with resection of intraabdominal Crohn's disease. PMID- 3112639 TI - Post-traumatic narcolepsy. PMID- 3112640 TI - Rucksack paralysis with and without rucksack frames. PMID- 3112641 TI - Salmonella cholerasuis infections in childhood. PMID- 3112642 TI - Case for diagnosis: a lung mass in an asymptomatic man. Pericardial cyst. PMID- 3112643 TI - Impetigo and other skin infections. PMID- 3112644 TI - [Apropos of a case of severe ischemia of the legs caused by ergotamine tartrate]. PMID- 3112645 TI - [Von Recklinghausen disease: presentation of a clinical case. Contribution to case material]. PMID- 3112646 TI - The processing of sheepskin for use as a dermal collagen graft--an experimental study. AB - In search of a biological mesh-prosthesis, sheepskin was processed according to established methods in the manufacture of leather. The dermal collagen fibre-mesh of sheepskin was purified by a proteolytic enzyme treatment after which the skins were split, providing a split-skin graft corresponding to the reticular layer of the dermis. The split-skin graft was subsequently tanned with a buffered glutaraldehyde solution (1.5% w/w, pH = 8, time of exposure 2 1/2 hrs, temp. 20 degrees C). Tannage was assessed by determination of the hydrothermal shrinkage temperature (Ts) of the grafts. Ts of the untanned grafts was 44.5 degrees C (n = 43, SD = 4.8). Glutaraldehyde tannage resulted in an elevation of Ts to 74.8 degrees C (n = 36, SD = 0.8). Untanned and tanned specimens were implanted subcutaneously in rats. Short-term (3-21 days) and long-term (6-36 weeks) survival periods were studied. The untanned graft evoked a minimal tissue response consisting of host fibroblasts and blood-vessels which had reinhabited the graft. In contrast, the tanned graft elicited a moderate degree of foreign body reaction and a greater fibroblastic and vascular response. The untanned graft had been absorbed by the 36th week, whereas the tanned graft had persisted, concurrently invoking the deposition of newly formed, fibrous collagen. The intended practical application of the glutaraldehyde tanned dermal collagen graft in surgery includes its use as a mesh-prosthesis, a wound dressing, a tendon or ligament substitute and as a vascular conduit. PMID- 3112647 TI - Bactericidal activity of peritoneal macrophages from continuous ambulatory dialysis patients. AB - A radiometric assay is described for measuring phagocytosis and intracellular killing of Staphylococcus epidermidis by peritoneal cells from continuous ambulatory peritoneal dialysis (CAPD) patients. Using this method it is possible to determine simultaneously and independently, in a single assay, whether peritoneal cells from CAPD patients possess defects in either ingestion or intracellular killing. Assays were performed on peritoneal cells obtained from 28 samples of spent dialysis fluid from CAPD patients. In the majority of cases these cells were able to efficiently phagocytose and kill opsonised Staph. epidermidis, although the degree of intracellular killing was slightly reduced compared with peritoneal cells obtained from eight normal controls undergoing laparoscopy. Overall there was no correlation between the degree of phagocytosis or intracellular killing and susceptibility of patients to peritonitis, although cells from two patients with a high incidence of peritonitis did show abnormally poor ingestion and/or killing. In a number of samples only low numbers of cells (less than 10(6)) were recovered in total from the overnight bags, and there was a significant inverse correlation between the number of cells in the fluid and the length of time on CAPD. PMID- 3112648 TI - Morbidity and mortality in diabetic and non-diabetic recipients of living related donor kidneys. AB - The results of kidney transplantation in juvenile-onset diabetic patients were compared to those of an age-matched control group of non-diabetic patients, all of whom were transplanted with kidneys from living related donors during the period 1977-1982, and managed by the use of conventional immunosuppression. The 5 year actuarial patient and graft survival rates did not differ significantly between the groups: 79% and 68% in diabetic patients and 88% and 72% in non diabetic patients, respectively. The graft function was stable in both diabetic and non-diabetic patients. Early surgical complications in both groups were few. Peripheral vascular insufficiency leading to amputation occurred only in diabetic patients, while hyperparathyroidism was recorded only in non-diabetic recipients. Primary cytomegalovirus infections were more common in diabetic patients. Providing good graft function was achieved, heart complications were a minor problem in both patient groups. However, cardiovascular complications were a leading cause of death in patients whose graft failed. The initial hospital stay was, on average, one week longer in diabetic patients, but the accumulated hospital stay in the three years following transplant was twice as long (1 month per year) in the diabetic group as in the non-diabetic. Rehabilitation during the last six months of follow-up was good in both groups and about 60% of diabetic and 90% of non-diabetic patients were working full- or part-time. Thus, the prospects for survival and rehabilitation were similar in diabetic and non diabetic patients in the 5 years following transplant, but at a higher price in diabetes. PMID- 3112649 TI - The use of intravenous and intraperitoneal desferrioxamine in aluminium osteomalacia. AB - A 32-year-old male with aluminium osteomalacia was changed from haemodialysis to chronic ambulatory peritoneal dialysis (CAPD) because of vascular access problems. Desferrioxamine (6 g) was administered intravenously on a once-weekly basis and the quantity of aluminium removed from each dialysate was calculated weekly. Aluminium concentration was estimated using the electrothermal atomic absorption spectrophotometer. The total aluminium removed after one week was 191 mumol, giving a clearance for aluminium of 4.2 ml per min. Subsequently intraperitoneal desferrioxamine 0.5 g per dialysate was administered to a total dose of 6 g and the cumulative aluminium loss was 134.1 mumol giving a clearance of 3.1 ml per min. The weekly loss of aluminium from dialysate when no desferrioxamine was administered was 58.3 mumol, giving a clearance of 2.5 ml per min. This is the first documented comparison of clearance rates for aluminium between CAPD alone, CAPD plus intravenous desferrioxamine and CAPD plus intraperitoneal desferrioxamine. PMID- 3112651 TI - Abstracts: annual meeting of the Irish Nephrological Society. Dublin, Eire, March 1986. PMID- 3112650 TI - On the mechanism and site of production of beta 2 microglobulin during haemodialysis. PMID- 3112652 TI - Aspects of new solutions for peritoneal dialysis. PMID- 3112653 TI - Long-term outcome of idiopathic membranous nephropathy with nephrotic syndrome. AB - We retrospectively studied 82 consecutive patients with idiopathic membranous nephropathy accepted at two separate Renal Services. These patients had nephrotic syndrome at presentation and had been followed up for at least 10 years. The duration of the disease before renal biopsy ranged between 1 and 18 months. Forty nine patients never received treatment (non-treated group) whereas 33 patients (treated group) received corticosteroids (and cytotoxic agents). The two groups were age and sex matched. There was no difference in clinical findings or in outcome between the two Renal Services. A complete and sustained remission of proteinuria was observed in about 25% of patients, and there was a significant difference (P less than 0.01) between the treated and non-treated group (mean value 39.1% vs 14.3%). Forty-four per cent of the non-treated patients and 24.2% of the treated ones developed chronic renal failure or renal death during a mean potential follow-up of 14 years. Non-renal death was recorded in 19.5% of the patients. The staging of the capillary wall lesion represented a very important prognostic index. We confirm, therefore, that idiopathic membranous nephropathy with nephrotic syndrome is frequently a progressive disease. Corticosteroids (and cytotoxic drugs) seem to be of some benefit in interfering with the natural course of the disease. PMID- 3112654 TI - Limited value of the fractional excretion of sodium test in the diagnosis of acute renal failure. AB - The excreted fraction of filtered sodium (FeNa) was examined in 54 patients with acute intrinsic renal failure in whom renal biopsy was performed to determine the morphology of the acute renal disease. In patients with acute tubulointerstitial nephritis oliguric patients had almost constantly elevated FeNa values, whereas in non-oliguric patients with acute tubulointerstitial nephritis this was observed in less than half. The five patients with acute extracapillary glomerulonephritis had an FeNa greater than 1. FeNa values were low, especially in non-oliguric patients who had mild impairment of renal function. The presence of a high FeNa value correlated significantly with severe morphological tubular changes observed on renal biopsy. We conclude that patients with acute tubulointerstitial nephritis cannot be distinguished from those with acute glomerulonephritis by FeNa, as in both types of acute nephritis the FeNa test shows both low and elevated values. PMID- 3112655 TI - Parathyroidectomy increases peripheral vascular responsiveness to exogenous noradrenaline in the uraemic rat. AB - The effect of surgical parathyroidectomy and/or cyclo-oxygenase inhibition on noradrenaline-induced blood pressure (BP) responses were investigated in a rat model of chronic uraemia. The blood pressure responses to noradrenaline were significantly lower in uraemic rats when compared with the responses of non uraemic animals. Blood pressure responses of previously parathyroidectomized uraemic rats were significantly greater than sham-operated uraemic rats, as were the responses of uraemic rats pretreated with the cyclo-oxygenase inhibitor, indomethacin. Pretreatment of uraemic rats with both indomethacin and parathyroidectomy improved blood pressure responses to a degree equal to either manoeuvre alone, but did not exhibit an additive effect. These data suggest a role for parathyroid hormone and prostaglandins in the pathogenesis of the diminished noradrenaline responsiveness in uraemia, and suggest a common mechanism. PMID- 3112656 TI - Monocyte-macrophage mediated suppression of erythropoiesis in renal anaemia. AB - To investigate monocyte-macrophages and their secretions in the pathogenesis of renal anaemia we studied the following in 12 uraemic patients and in 12 normal subjects: 1. in vitro proliferation of erythroid progenitors (BFU-e) from uraemic and normal peripheral whole mononuclear cells; 2. effects of monocyte-depletion of uraemic or normal whole mononuclear cells on proliferation of BFU-e; 3. effects of adding uraemic or normal peritoneal macrophages (PM0) to peripheral blood normal non-adherent mononuclear cells; and 4. Interleukin-1 (IL-1) and prostaglandin E2 (PGE2) concentrations in supernatants of uraemic and normal PM0. BFU-e growth from uraemic whole mononuclear cells is lower than that of normal whole mononuclear cells. The removal of monocytes induces an increase in BFU-e development in uraemic patients, but a decrease in normal subjects. The addition of uraemic PM0 to normal nonadherent mononuclear cells causes a decrease in BFU-e formation, compared to values incubating normal PM0. PGE2 release in supernatants of uraemic PM0 is greater than in supernatants of normal PM0, and IL-1 activity is less with uraemic PM0 than that with normal PM0. In Conclusion we found that uraemic monocyte-macrophages have a suppressive effect on BFU-e development in vitro which can be mediated by abnormal release of secretory products. PMID- 3112657 TI - The influence of dialysis fluid composition on dialysis tolerance. AB - To evaluate the role of bicarbonate loss through the dialyser and acetate flux to the patient in the development of symptoms during acetate dialysis, bicarbonate loss during acetate dialysis was prevented by using a combination of acetate and bicarbonate in the dialysate. Seven uraemic patients were treated for 4 months with acetate dialysis and, successively, for a similar period of time with bicarbonate, and a combination of acetate and bicarbonate dialysis. Blood pressure drop and the incidence of hypotension and symptomatic episodes were similar in bicarbonate and combination dialysis, and significantly lower than in acetate dialysis. Serum acetate concentrations were similar during acetate and combination dialysis. These findings indicate that bicarbonate loss rather than the presence of acetate was responsible for the patients' intolerance to acetate dialysis. PMID- 3112658 TI - Influence of left ventricular function on changes in plasma volume during acetate and bicarbonate dialysis. AB - The effect of left ventricular function on changes in plasma volume during acetate and bicarbonate dialysis was studied in stable, chronic dialysis patients. Preservation of plasma volume in patients with a normal left ventricular function (mean circumferential fibre shortening velocity (VcF) greater than or equal to 1 circ/s) was significantly less during the first hour of acetate dialysis than during bicarbonate dialysis. However, in patients with impaired left ventricular function (VcF less than 1 circ/s) the decrease in plasma volume was more pronounced during acetate when compared to bicarbonate dialysis. This resulted in a decreased ultrafiltration volume and haemodynamic instability in these patients during acetate dialysis. The fibre shortening velocity increased during acetate and bicarbonate dialysis in patients with a normal left ventricular function, whereas in patients with impaired left ventricular function fibre shortening velocity increased only during bicarbonate dialysis. In conclusion, in patients with an impaired left ventricular function, bicarbonate is preferable to acetate in chronic dialysis. PMID- 3112661 TI - Role of the head nurse. PMID- 3112659 TI - Amyloid scrapie plaques in mice, and Alzheimer senile plaques, share common antigens with tau, a microtubule-associated protein. AB - Immunolabelling was performed on brain sections of scrapie-infected mice with antibodies against tau, a microtubule-associated protein, and against the paired helical filaments of Alzheimer's disease. Both kinds of antibodies have been shown previously to label paired helical filaments in neurons and in abnormal neurites associated with the senile plaques of Alzheimer's disease. Amyloid plaques in murine scrapie were labelled by both antisera. The structural substrate for the immunolabelling was probably the dystrophic neurites in the periphery of the plaques, leaving the amyloid core unstained. These results emphasize that similar mechanisms are likely to be involved in the pathogenesis of plaques in both diseases. PMID- 3112660 TI - Primary resistance to antituberculous drugs in a New Jersey hospital. PMID- 3112662 TI - Special time. PMID- 3112664 TI - Carbon dioxide laser surgery of female genital, perineal, and anal condyloma acuminata. PMID- 3112665 TI - The dimensions of dentistry: how much do New Zealanders spend on dental care? PMID- 3112666 TI - Nursing productivity: evolution of a systems model. PMID- 3112667 TI - Factors related to job satisfaction/dissatisfaction of registered nurses in long term care facilities. PMID- 3112668 TI - DRGs ... an impediment. PMID- 3112669 TI - Primary gastrointestinal lymphoma. AB - Sixteen cases of primary malignant lymphoma of the gastrointestinal tract were reviewed because of some controversy concerning its proper management. An intraabdominal disease staging system with prognostic correlation was used. Treatment employed was either (biopsy plus) irradiation alone or surgical resection of abdominal neoplasm with postoperative radiotherapy. Conventional megavoltage locoregional or subtotal/whole abdomen irradiation with an often given total dosage of 3,000-4,000 cGy up to 5.5 weeks was applied. Overall 4-year disease-free survival rate was 71%. Operative removal of neoplasm appeared important for an improved prognosis. Definitive radiotherapy alone did not have a dismal outcome. PMID- 3112670 TI - Priming action on progesterone receptor synthesis by estradiol and tamoxifen in the 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinoma. AB - The priming action of estradiol and the antiestrogen tamoxifen (TMX) on progesterone receptor (PgR) synthesis has been investigated in the 7,12 dimethylbenz(a)anthracene-induced rat mammary tumor model testing different priming times. Rats received either TMX or estradiol benzoate (E2B) for 3 or 7 days. Tumors were assayed before and after treatment to investigate the changes produced by each treatment on estrogen receptor (ER) and PgR concentration. As expected, ER concentration decreased in each treatment group. PgR concentration increased after 3 days of either E2B or TMX administration, but decreased when treatment was prolonged to 7 days. These findings point out the time dependency of PgR induction in this tumor model, similarly to what was observed in other experimental and clinical conditions. PMID- 3112671 TI - [Dynamics of 3H-lysine incorporation into the retinal ganglion cells of the ground squirrel (Citellus pygmaeus Pallas) in active state and during hibernation]. AB - Circahoralian rhythm of the intensity of 3H-lysine incorporation into proteins of the retina ganglionic cells and of the protein synthesis rate in the isolated retina with an amplitude of fluctuations of 35-36% of the mean has been found in active adult susliks. During hibernation, no circahoralian fluctuations of protein metabolism were recorded. Circahoralian rhythms of protein metabolism can serve as a marker of the tissue functional activity. PMID- 3112673 TI - The proposed Joint Commission risk management standard: evolution or revolution? PMID- 3112672 TI - Infectious flare-ups and serious sequelae following endodontic treatment: a prospective randomized trial on efficacy of antibiotic prophylaxis in cases of asymptomatic pulpal-periapical lesions. AB - Without peritreatment antibiotics, infectious flare-ups (about 15% incidence) and serious sequelae follow endodontic treatment of asymptomatic teeth with necrotic pulps and associated periapical lesions. Antibiotics administered after endodontic treatment (4-day regimen) reduce the flare-up incidence to about 2%, but hypersensitivity responses, sensitization, resistant microbes, and drug taking compliance are potential problems. To ascertain whether a specific prophylactic antibiotic (high-dose, 1-day regimen) would preferentially maintain this low flare-up incidence while overcoming antibiotic-related problems, 315 patients with quiescent pulpal necrosis and an associated periapical lesion were randomly given either penicillin V or erythromycin (base or stearate). Evaluations of flare-up after endodontic treatment were done at 1 day, 1 week, and 2 months. A 2.2% flare-up incidence was found, with no statistically significant differences for penicillin (0.0%), base (2.9%), and stearate (3.8%). No hypersensitivity responses occurred. Gastrointestinal side effects were found primarily with the erythromycins (12.4%). A comparative analysis of the data from our first study (no peritreatment antibiotics) and the pooled data from our last two investigations (including the current trial) showed that peritreatment antibiotic coverage significantly reduced flare-ups and serious sequelae after endodontic treatment (p less than 0.001). PMID- 3112674 TI - The hospital medical staff of 1997. PMID- 3112675 TI - Medical staff privileging: how to avoid pitfalls in the administrative process. AB - In a climate in which medical staffs are being sued as a result of their decisions in peer review activities, hospitals' administrative and medical staffs are becoming more cautious in their approach to medical staff privileging. Medical staff bylaws that contain substantive and procedural requirements serve as guides to the privileging process. The Health Care Quality Improvement Act of 1986 sets standards for peer review activities; the Act also provides limited immunity for peer review. PMID- 3112676 TI - Quality assurance and risk management in small and rural hospitals: the roles of trustees, administration, and medical staff. AB - Small and rural hospitals have unique considerations that affect their approach to quality assurance (QA) and risk management (RM). These concerns include proportionately high fixed costs, small patient loads that limit their ability to balance profits and losses from Medicare patients, small medical staffs that limit their ability to provide peer review, and the general increase in malpractice litigation. QA and RM programs are critical to the survival of these hospitals, but they should be integrated as much as possible with other hospital activities. PMID- 3112677 TI - Delineating clinical privileges. AB - Clinical privilege delineation is essential in assuring quality care and minimizing the liability exposure of an institution and its staff. Approaches to privilege delineation include: delineation by practitioner specialty; delineation by patient risk categories; delineation using a list of procedures; and approaches combining these three methods. Regardless of the approach taken, the key to effective privilege delineation is that specific written criteria be applied uniformly to all individuals. Some of the difficulties encountered in the privilege delineation process involve granting privileges for new procedures, monitoring compliance with privileges, and granting privileges that may be performed by members of several departments. PMID- 3112678 TI - Impact of exclusive contracts on medical staff bylaws. PMID- 3112679 TI - [Possibilities of prenatal diagnosis of hemophilia A]. PMID- 3112680 TI - The facial nerve in the infratemporal approach. AB - A new method of re-routing the facial nerve in the infratemporal fossa approach is presented. Exposure of the skull base is not compromised and better immediate and long-term facial function is achieved. A consecutive series of 31 cases is discussed. PMID- 3112681 TI - Successful replantation of amputated nose and auricle. AB - Amputations of the nose and of the auricle present difficult management problems. Application of simple reattachment techniques, followed by aggressive medical therapy which consists of cooling, anticoagulation, antibiotic coverage, and multiple stab incisions in the amputated tissues, have resulted in the successful replantation of major portions of an amputated nose and an amputated auricle with satisfactory cosmetic results. PMID- 3112682 TI - The folded trapezius flap for through-and-through cheek defects. AB - A through-and-through defect of the cheek is a reconstructive challenge- functionally, technically, and cosmetically. The goal of reconstruction is to reliably and expediently bridge a poorly vascularized gap with healthy tissue. Since 1979, five patients have undergone folded trapezius flap reconstruction of the cheek. Despite a history of radiation in four of the five, all flaps have healed and complications have been minimal. The key to success seems to be careful attention to the venous drainage. This technique provides a one-stage reconstruction of a difficult surgical defect. PMID- 3112683 TI - Laryngeal chemoreflex: anatomic and physiologic study by use of the superior laryngeal nerve in the piglet. AB - The laryngeal chemoreflex (LCR) was investigated in 21 piglets (ages 6 to 80 days old) with the use of physiologic and histologic techniques. The central projection of the superior laryngeal nerve (SLN) was determined in 14 animals by use of horseradish peroxidase-wheat germ agglutinin. Ipsilateral labeling of the solitary tract nucleus was seen. The caudal extent of the labeling varied with age. Sensory labeling of the nucleus ambiguus was present bilaterally in three younger animals and unilaterally in older piglets. Bilateral labeling of the nucleus dorsomedialis was seen in all ages. Apneic and cardiovascular response to water stimulation of laryngeal mucosa and the laryngeal adductor reflex (LAR) were examined in 16 piglets. Blunting of the apneic and cardiovascular response was seen after sacrifice of a single SLN. Hypoxia did not significantly affect the LAR or apnea duration in animals with only one intact SLN. A contralateral LAR was found in younger animals. Relevance to the LCR is also discussed. PMID- 3112684 TI - Oncocytic Schneiderian papilloma in a young adult: a rare diagnosis. AB - The oncocytic Schneiderian papilloma (OSP) is a rare neoplasm of the nose and paranasal sinuses. The majority of the approximately twenty patients reported in the literature with this papilloma have been over the age of fifty at the time of diagnosis. The 33-year-old woman reported here is the youngest patient with this lesion to date. The OSP should be considered in the work-up of all unilateral nasal polypoid lesions. This lesion's propensity for recurrence and its documented association with synchronous malignant disease warrant surgical excision by en bloc resection of the lateral nasal wall, with corresponding careful microscopic evaluation of all excised tissue. PMID- 3112685 TI - Neural choristoma of the middle ear. PMID- 3112686 TI - Osteoma of the middle ear: a case report. PMID- 3112687 TI - Bilateral deep space neck abscesses complicating infectious mononucleosis. PMID- 3112688 TI - Tumoral calcinosis in the neck. AB - Tumoral calcinosis manifests soft-tissue calcification, usually near major joints. It variably includes hyperphosphatemia, elevated 1,25 dihydroxycalciferol, and an affected sibling. Serum calcium, alkaline phosphatase, and parathyroid hormone are normal. Tumoral calcinosis of the head and neck is very rare, but this diagnosis should be considered when x-ray film of a poorly defined mass shows irregular soft-tissue calcification. PMID- 3112689 TI - Acute airway obstruction due to a benign cervical goiter. PMID- 3112690 TI - Invasive congenital hemangiomas of the nose. PMID- 3112691 TI - Posterior wall pharyngectomy with preservation of laryngeal function. PMID- 3112692 TI - Radial forearm flap for reconstruction of oral cavity defects. PMID- 3112693 TI - Bilateral multiple benign lymphoepithelial cysts of the parotid gland. PMID- 3112695 TI - Annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. Chicago, Illinois, September 19-23, 1987. Abstracts. PMID- 3112694 TI - Tuberculosis of the soft palate: an unusual presentation of oral tuberculosis. PMID- 3112696 TI - Congress explores reimbursement alternatives. PMID- 3112697 TI - A child with Hurler syndrome. PMID- 3112698 TI - [Recommendations for parenteral infusion and nutritional therapy in childhood]. PMID- 3112699 TI - [Effect of long-term preventive use of TMPS on the composition and resistance behavior of aerobic fecal flora]. AB - Trimethoprim Sulfa is a valuable agent in the prophylaxis of Pneumocystis carinii pneumonia in immunocompromised children. Like several other antimicrobial substances also TMPS has an impact on the normal bacterial flora of children. TMPS sensitive enterobacteria are eliminated from the gut flora within 48 hours. The impact on the total number of aerobic organisms and the composition of the fecal flora however is just moderate. Major changes in gut flora result from previous administration of antibiotic and chemotherapeutic agents or from environmental changes (e. g. discharge into ambulatory care). The gut flora of patients under such chemoprophylaxis is a major source of TMPS resistant aerobic bacteria in the hospital and requires careful disposal of these wastes. PMID- 3112700 TI - Isolation of Theileria parasites from African buffalo (Syncerus caffer) and characterization with anti-schizont monoclonal antibodies. AB - Antigenic differences between intra-lymphocytic theilerial parasites isolated from the blood of 18 African buffalo and grown in vitro were assessed with anti schizont monoclonal antibodies (mAbs). There was marked antigenic diversity both between isolates from different buffalo and between isolates taken at different times from the same buffalo. Many of the isolates from both wild and captive buffalo appeared to consist of mixed parasite populations. Some isolates were found by limiting dilution cloning and mAb testing to contain at least 3 or 4 distinct populations of Theileria. Once cloned, Theileria-infected lymphoblastoid cell lines retained their mAb profiles during prolonged in vitro cultivation and, when recloned, the subclones had the same mAb profile as their parent clone. The implications of these results for further studies on buffalo-derived theilerial parasites are discussed. PMID- 3112701 TI - Experimental induction of Theileria parva lawrencei carrier state in an African buffalo (Syncerus caffer). AB - An African buffalo (Syncerus caffer), born in captivity and demonstrated to be Theileria-free, and 2 susceptible cattle were inoculated with a Theileria parva lawrencei sporozoite stabilate. The buffalo had a very mild disease reaction, while the 2 cattle died of acute theileriosis. It was possible to isolate T. p. lawrencei from the buffalo up to 888 days after infection by the application of non-infected Rhipicephalus appendiculatus nymphs and up to 657 days after infection by the establishment of lymphoblastoid cell lines infected with T. p. lawrencei schizonts from peripheral mononuclear blood cells. The infection rate and levels of Theileria in the resultant adult ticks varied from 11 to 70% with 0.3-11 acini infected/tick. Stabilates prepared from these tick batches caused fatal T. p. lawrencei infections in cattle. PMID- 3112702 TI - Development and survival of Theileria parva parva in Rhipicephalus appendiculatus exposed in the Trans-Mara, Kenya. AB - Nymphal Rhipicephalus appendiculatus (Trans-Mara) were fed on a steer infected with a Theileria parva parva (Kilae 1) stock isolated from an indigenous steer in the Trans-Mara Division, Kenya, which had a high piroplasm parasitaemia. A total of 5000 engorged nymphs which had dropped on one day were enclosed in elongated nylon bolting silk tubes in groups of 200-300 and were transported immediately to the Trans-Mara where they were suspended vertically in the grass cover with one end touching the ground. Over 98% of the nymphs moulted into adult ticks and 50% moult occurred by day 28 after exposure. The ticks showed over 80% survival up to 308 days post-exposure but thereafter showed a marked mortality so that only 22.5% of the ticks were alive after 439 days. Theileria parasites were detected in the salivary glands by day 35 post-exposure and infection rates and levels increased markedly between 180 and 235 days post-exposure. Thereafter, the infection rates and levels generally decreased. Groups of ticks were triturated and the resultant supernatant fluid inoculated into pairs of susceptible cattle, and these proved infective from day 44 to 145 after exposure. Three subsequent attempts to induce infections with supernatant fluid were unsuccessful. From 294 days after exposure, groups of 50 ticks were applied to cattle and caused lethal T. p. parva infections up to 439 days post-exposure. Climatic observations showed a relatively even monthly rainfall as well as mean maximum and minimum monthly temperatures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112703 TI - Passive transfer of resistance to mice with sera from rabbits, rats or mice vaccinated with ultraviolet-attenuated cercariae of Schistosoma japonicum. AB - All serum transfers from donor rats or rabbits given single or multiple vaccinations of ultraviolet (u.v.)-attenuated Schistosoma japonicum cercariae conferred significant resistance against challenge to mice. Donors given 5 vaccinations, however, produced the most effective sera; rat sera giving up to 88% protection and rabbit sera up to 80%. This protective effect was species specific and titratable. Sera from vaccinated rabbits and rats were were most effective when transferred to mice 2 h before challenge, but became progressively less effective when transferred with increasing time after challenge. These sera had no efficacy when given 6 days after challenge. Thus, sera from vaccinated rabbits and rats were effective against the early stage of migration, but did not necessarily have to act in the skin as all serum transfers were as effective against intraperitoneal as percutaneous challenge. By contrast, serum from multiply vaccinated mice had little or no protective effect when transferred to mice before challenge, but conferred 62% resistance when transferred 5 days after challenge. Further, there was an additive protective effect when vaccinated rat and mouse sera were given in combination at their optimum transfer times (days 0 and +5, respectively). Thus, there appears to be a stage-specific immune response induced by vaccination depending upon whether the vaccinated hosts are truly permissive or not. Vaccinated rats and rabbits respond to the early phase of migration and vaccinated mice make protective responses against the lung phase of migration. PMID- 3112704 TI - The isotypes of antibody responsible for the 'late' passive transfer of immunity in rats vaccinated with highly irradiated cercariae. AB - The role of different antibody isotypes in the transfer of protection with serum from rats vaccinated with irradiated cercariae were investigated by immunoadsorption of IgG, IgG2a and IgG2c, and by heating at 56 degrees C to remove IgE. Only depletion of IgG2a reduced the levels of vaccine-induced immunity transferred, whereas immunity transferred by infection serum was reduced by both IgG2a and IgE depletion. It was also shown that exposure to irradiated parasites did not lead to either specific or non-specific induction of an IgE response. The successful passive-transfer experiments using serum from non resistant 25 week-infected rats into recipient animals demonstrated that the waning of resistance observed in 25 week-infected rats was not due to a failure of the humoral response to protective antigens. PMID- 3112705 TI - [Study of the sensitivity to pipemidic acid, pefloxacin and norfloxacin of 444 bacterial strains isolated at a general hospital]. AB - After one year of use of pefloxacin in the intensive care unit, medicine unit and surgery unit and the following recent commercialization without prescription of norfloxacin, we studied for a period of two months (april and may 1986) the susceptibility to pipemidic acid, to pefloxacin and norfloxacin of 444 bacteria strains isolated obtained from clinical specimens. The antibiotic susceptibility is determined by disk diffusion test. We obtained the following results: susceptible methicillin Staphylococcus aureus (SMSA 63 strains): 85.7% PEFS, 11.1% PEFI, 79.4% NORS, 15.9% NORI, resistant methicillin Staphylococcus aureus (RMSA 36 strains): 33.3% PEFS, 2.9% PEFI, 41.6% NORS, 0% NORI; Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae (252 strains): 94% PIPS, 94.8% PEFS, 97.2% NORS; Enterobacter, Proteus indol (+), Providencia and Citrobacter (33 strains): 72.7% PIPS, 72.7% PEFS, 84.8% NORS; Pseudomonas aeruginosa (53 strains): 32% PEFS, 47.2% PEFI, 90.6% NORS, 5.6% NORI; Acinetobacter (7 strains): 57.2% PEFS, 42.8% PEFI, 42.8% NORS, 28.6% NORI. Norfloxacin in active in vitro against the majority of the P. aeruginosa isolated. We found an important methicillin and pefloxacin resistance among the Staphylococcus aureus isolated: 36 strains RMSA (36.4% out of Staphylococcus aureus) and 23 strains RMSA PEFR (63.8% out of RMSA). These later strains were isolated in eight different units mainly in visceral surgery unit and geriatric units but not in intensive care unit. After an epidemiologic study and the following recommendations to physicians and nurses: treatment by pefloxacin should be used only after bacteriological results and associated with an other antibiotic, the handwashing should be frequent and regular to prevent the spread of infection, four months later we isolated 26 strains of RMSA with 7 RMSA PEF (26.9%).2$ PMID- 3112706 TI - [In vitro activities of 9 aminosides against of 250 strains of Neisseria gonorrhoeae]. AB - We compared the in vitro activities of 9 aminoglycosides including trospectomycin sulfate against 250 selected strains of Neisseria gonorrhoeae according to their penicillin resistance (penicillinase production), streptomycin resistance, spectinomycin resistance. Trospectomycin sulfate inhibited all spectinomycin sensible strain at a concentration of 4 mg/l but the spectinomycin-resistant strain needed 32 mg/l for its inhibition. Among the other aminoglycosides tested netilmicin had the most in vitro effectiveness. Its minimal inhibitory concentrations were comparable to that of trospectomycin sulfate: furthermore this compound demonstrated in vitro activity against the spectino-resistant strain. PMID- 3112708 TI - [In vitro sensitivity at 18 antibiotics of 192 strains of Pseudomonas aeruginosa isolated at Garches Hospital]. AB - The in vitro activity of 18 antibiotic (beta-lactam agents, quinolones and aminoglycoside has been evaluated against 192 clinical isolates of Pseudomonas aeruginosa. Minimal inhibitor concentrations (MICs) were determined by the agar dilution technique. The 50% and 90% MICs were respectively: ticarcillin (32/greater than 1 024), azlocillin (16/512), piperacillin (8/512), cefsulodin (4/128), ceftazidime (2/8), aztreonam (4/16), imipenem (2/4), nalidixic acid (128/256), pefloxacin (1/8), norfloxacin (1/8), ofloxacin (2/8), ciprofloxacin (0.25/2), gentamicin (8/256), sisomicin (4/256), tobramycin (2/128) dibekacin (4/256), netilmicin (16/256), amikacin (8/16). The sensitivity to beta-lactam agents and to quinolones was usual. Resistance to aminoglycosides was frequently observed (59%): 35.7% of the resistant isolates were resistant to gentamicin sisomicin-tobramycin-dibekacin-netilmicin, 30% to netilmicin alone, 17.8% to gentamicin-sisomicin-tobramycin-dibekacin-netilmicin-amikacin, 7% to gentamicin netilmicin, 5.3% to gentamicin-sisomicin-tobramycin-dibekacin; we did not find any P. aeruginosa resistant only to gentamicin or gentamicin-sisomicin. PMID- 3112707 TI - [Profiles of resistance to aminosides of Pseudomonas aeruginosa]. AB - Among all Gram-negative bacilli, Pseudomonas aeruginosa is one of the most resistant to aminoglycosides. Five hundred and seventeen P. aeruginosa strains were studied. Isolates came from three Paris hospitals. Reference strains were provided by P. Courvalin and A. Philippon. The following aminoglycosides were used: streptomycin (S), spectinomycin (Sp), kanamycin (K), neomycin (N), gentamicin (G), sisomicin (Ss), netilmicin (Nt), tobramycin (T), amikacin (A), habekacin (H). The in vitro activity of antibiotics was evaluated by the standardized disk agar diffusion test. Distribution of inhibition zone diameters among susceptible strains were represented by histograms. Resistance frequency to aminoglycosides was: G: 61.5%, Ss: 38.1%, T: 35.8%, Nt: 58.2%, A: 15.5%, Seven resistance patterns were identified: G: 3%, G Ss: 3%, G Nt: 8%, G Ss Nt: 7%, G Ss T: 5%, G Ss T Nt: 53%, G Ss T Nt A: 21%. Hypothesis about resistance mechanisms and interpretation of disk agar diffusion test are discussed. PMID- 3112709 TI - [Resistance of Listeria monocytogenes to cefotaxime and ceftriaxone combined with an aminoside]. AB - The in vitro antibacterial activity of cefotaxime and ceftriaxone-aminoglycoside combinations was studied against 20 clinical isolates of Listeria monocytogenes, and compared with the activity of the antibiotics alone. Minimal bacteriostatic and bactericidal concentrations (MBCs) as well as killing curves were determined using different parameters. In all cases, the MBCs of gentamicin and netilmicin were shown to be lowered by addition of CTX or CTR. Using Mueller-Hinton broth the values of MBCs obtained were achievable in the CSF. However, the clinical bearing of these results remained to be discussed. PMID- 3112710 TI - [In vitro study of the combination of pefloxacin with other antibiotics against Pseudomonas aeruginosa and Streptococcus group D]. AB - The comparative susceptibility of 50 isolates of enterococci and 50 isolates of Pseudomonas aeruginosa to pefloxacin and different antibiotics was tested using MIC determination. The results showed only 6% sensitive strains of enterococci and 36% of P. aeruginosa. The high level resistant streptococci against aminoglycosides and resistant Pseudomonas strains have weakly higher MIC than sensitive strains. The activity of the combination of pefloxacin and other antibiotics was determined by a checkerboard micromethod. Fractional concentration index (FIC and FBC) show most frequently addition, uncommonly synergy. PMID- 3112711 TI - [Study of bactericidal effect of the spiramycin and minocycline on Mycoplasma pneumoniae]. AB - This study was designed to determine if the inhibitory effect of a macrolide (spiramycin) and a tetracycline (minocycline) on the in vitro growth of Mycoplasma pneumoniae is due to a bacteriostatic or a bactericidal activity. M. pneumoniae, strain FH-Liu, susceptible to spiramycin and minocycline was exposed to various inhibitory concentrations of these antibiotics (within the range of 0.5-32 mg/l) for various periods of time (1-9 days). The bactericidal activity was determined by subculturing material from tubes using serial dilution. Spiramycin was bactericidal after 4 days (greater than or equal to 3 log10 decrease of the inoculum) only when high concentrations were used (16 mg/l). Minocycline was bactericidal after 4 days at a concentration of 32 mg/l. These results show a 64-fold difference between minimum inhibitory concentration and minimum bactericidal concentration for spiramycin and a 128-fold difference for minocycline. Our data confirm the bacteriostatic effect of these drugs on M. pneumoniae. PMID- 3112712 TI - [Effects of loperamide on the fecal flora in children in severe diarrheas]. AB - Loperamide has been recently indicated in the management of infants with severe protracted diarrhea. The purpose of this study was to determine the effect of loperamide on fecal flora in severe protracted diarrheas. 19 children aged 1 to 36 months, with severe protracted diarrhea were studied: 14 received loperamide (0.5 mg/kg/d) and 5 were without loperamide treatment. Criteria analysed were: clinical tolerance (vomiting and abdominal distention); efficacy (number of stools, transit time and Na+/K+ in stools) and effect on fecal flora, with differential qualitative and quantitative analysis method (complete identification and counts of aerobic and strict anaerobic bacteria in fresh fecal samples before and 4 to 8 days after the beginning of loperamide). Parenteral and/or oral alimentation remain constant during the study. Results show a rapid (24 h) efficacy in 9/14. Although important changes in specific fecal flora counts was noticed for streptococcus D and Proteus as compared to five controls, no bacterial overgrowth appeared or was increased during loperamide treatment. PMID- 3112713 TI - [Prophylactic antibiotherapy in biliary surgery, cefazolin versus cefoperazone. Randomized comparative open study in a population at risk for infection]. AB - Sixty patients having to undergo a biliary operation with high risk of infection (Keighley's criterions) received at random either cefazolin (CFZ) or cefoperazone (CFP) as a prophylactic antibiotherapy. Postoperative courses were fairly normal: a peak of temperature on day 5 for one case and a digestive bleeding due to hypoprothrombinemia for another case. No further complication occurred. Patient discharge was two days shorter with cefoperazone and biliary positive cultures were in favour of cefoperazone (21% with CFZ, 11% with CFP) but without statistically significant level. Consequently, this trial should be carried out on a larger scale. PMID- 3112714 TI - [Effect of aztreonam on the fecal aerobic flora in children]. AB - Aztreonam, a new monobactam, has a spectrum limited to Gram negative aerobic bacilli. To evaluate its effect after parenteral administration on aerobic stool flora (Gram negative bacilli, Streptococci D, Staphylococci, Candida), quantitative cultures used serial dilution of stools twice a week on selective media. For Gram negative bacilli, agar dishes containing aztreonam or not were used. Colonies of different morphologies were counted. Representatives of each morphological type were then picked for identification and susceptibility tests. Among the 16 patients treated, 12 were decontaminated for aerobic gram negative bacilli by the 3rd day. Sensitive bacteria persisted in 4 cases, although at a low level. Resistant bacteria (Enterobacter cloacae and Acinetobacter) appeared at a "normal" level in 2 patients initially decontaminated. No dramatic change could be detected for Streptococci D, Staphylococci and Candida. In twelve additional infants neither hospitalized nor treated, no aztreonam resistant Gram negative bacilli could be found. PMID- 3112715 TI - [Evaluation of the specific activity of hyperimmune anti-Pseudomonas aeruginosa human plasma in an experiment]. PMID- 3112716 TI - Structure and genetics of antibody. PMID- 3112717 TI - Diabetic ketoacidosis. Biochemistry, physiology, treatment, and prevention. AB - Diabetic ketoacidosis (DKA) is the most common cause of death of juvenile-onset diabetics, and as such represents an important issue for pediatricians. In this article, the author reviews the endocrinology of insulin and the glucose counter regulatory hormones, which are the basis for the development of DKA. The effects of hyperglycemia and acidosis upon organ physiology are detailed, and this serves as the foundation for subsequent discussion of the management of the patient with DKA. Finally, the author summarizes current strategies for prevention of DKA in patients with diabetes. PMID- 3112718 TI - Phosphorus deficiency syndrome in very low birth weight infants. AB - Inadequate dietary phosphorus intake is a contributing factor to the occurrence of metabolic bone disease in very low birth weight infants. This article reviews the clinical presentation and the pathophysiology of the phosphorus deficiency syndrome in premature infants. Recommendations for therapy and prevention of phosphorus deficiency are presented. PMID- 3112719 TI - The gastrostomy feeding button. PMID- 3112720 TI - Sodium cromoglycate and carbachol-induced bronchoprovocation in asthmatic children. AB - Ten children with mild bronchial asthma underwent bronchial challenge with carbachol on three consecutive days; using a double-blind technique, they were given inhaled saline placebo on the first day and placebo or sodium cromoglycate (SCG) on the second and third days 15 min prior to the bronchial provocation test with carbachol. We did not find any significant difference between the baseline and placebo values, but we did obtain a statistically significant difference when comparing baseline with post-SCG and placebo with post-SCG values. These results demonstrate a protective effect of SCG on carbachol-induced bronchospasm in asthmatic children. PMID- 3112721 TI - [Use of somatocrinin (GRF), the growth hormone releasing neurohormone, as a diagnostic test in the differential diagnosis of the hypothalamic and pituitary forms of somatotropin insufficiency of the pituitary gland]. PMID- 3112722 TI - Intravenous immunoglobulin in the treatment and prevention of acute infections in pediatric acquired immunodeficiency syndrome patients. PMID- 3112723 TI - Prevention of pneumococcal bacteremia in a child with acquired immunodeficiency syndrome-related complex. PMID- 3112724 TI - Carbamazepine intoxication following the use of erythromycin in children. PMID- 3112725 TI - Failure to eradicate Malassezia furfur broviac catheter infection with antifungal therapy. PMID- 3112726 TI - Community-acquired Pseudomonas sepsis in previously healthy infants. PMID- 3112728 TI - Rudimentary testes syndrome revisited. AB - Sixteen children who were one day to 9 years of age underwent clinical, anatomic, and hormonal study because of extreme hypoplasia of the phallus and small testes associated with normal 46XY male karyotype. Two of them were first cousins. All patients had Leydig cell deficiency. Among 15 patients who received luteinizing hormone-releasing hormone stimulation during childhood, 11 had an exaggerated response of either one or both gonadotropins. Bilateral biopsy, performed in eight patients, showed a clearly testicular structure with either scant or incompletely differentiated tubules. These characteristics allow clear differentiation from chromosomal abnormalities and malformation syndromes. It is more difficult to differentiate between rudimentary testes and primary gonadotropic deficiencies and may not be possible until the child has reached adolescence. The syndrome of rudimentary testes may be a manifestation of XY primary gonadal dysplasia, along with pure XY gonadal dysgenesis, XY hermaphroditism, XY mixed gonadal dysgenesis, and congenital anorchia, probably resulting from fetal regression of the testes. The observed familial occurrence of the syndrome of rudimentary testes, as well as of XY gonadal dysgenesis, leads to speculation about the possibility of X-linked transmission. PMID- 3112727 TI - Psychologic and behavioral effects of antiepileptic drugs in children: a double blind comparison between phenobarbital and valproic acid. AB - Traditional clinical monitoring of children with epilepsy does not appear to be sufficiently sensitive to cognitive functioning and behavioral problems. Although subtle, these changes may alter a child's ability to perform well in school and in society. Physicians must prevent seizures without producing intolerable side effects, and ways of more appropriately assessing these side effects must be developed. In this double-blind, counter-balanced, crossover study of 21 children, the effects of phenobarbital and valproic acid on cognitive functioning and behavior were measured. There was no difference in seizure control between the drugs, and each medication was maintained in the therapeutic range for 6 months (mean phenobarbital level, 21.2 micrograms/mL; mean valproic acid level, 94.1 micrograms/mL). Children were treated with each drug for 6 months. Differences between the drugs were seen on measurements of cognitive function and behavior. On four tests of neuropsychologic function, children performed significantly less well while receiving phenobarbital (P less than .01). There was no evidence that the patients were sedated or less able to perform continuous performance tasks while receiving phenobarbital. Parental assessment of behavior indicated significantly worse behavior with the phenobarbital regimen for three items (P less than .01) and children were measurably more "hyperactive" (P less than .05). Routine clinical assessment of the patients did not reveal differences between the drugs with respect to routine laboratory measurements or side effects as assessed by history or physical examination. Although children may appear to tolerate a medication without clinically apparent problems, subtle but significant changes in intellectual function and behavior may be occurring. Additional, more sensitive, methods of monitoring patients while receiving these drugs is necessary. PMID- 3112729 TI - Immunogenicity of Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine in 2- to 6-month-old infants. AB - Fifty infants, 2 to 6 months of age, were vaccinated with Haemophilus influenzae type b capsular polysaccharide covalently linked to an outer membrane protein from Neisseria meningitidis group B. Subjects were given two injections and were randomly assigned to receive the injections separated by 1 or 2 months. Each dose contained 15 micrograms of polysaccharide and 51 micrograms of protein, or approximately twice the amount of polysaccharide as used in our previous trial (Lancet 1986;2:299). Fevers of 38.0 degrees to 38.8 degrees C developed in three infants (6%) within 24 hours after vaccination, but there were no other notable reactions. Following one injection, the geometric mean antibody concentration increased from 0.13 micrograms/mL in preimmune serum to 1.50 micrograms/mL in serum obtained 1 to 2 months later (P less than .001). After a second injection, there was a further increase in serum antibody (geometric mean = 3.11 micrograms/mL, P less than .007). The geometric mean antibody concentration of the group reimmunized 2 months after the first injection was higher than that in the group reimmunized after 1 month (3.95 v 2.32 micrograms/mL, P = .05, by analysis of covariance with age as the covariant). These data confirm our previous preliminary observations on the safety and immunogenicity of this new conjugate vaccine in infants 2 to 6 months of age. The data suggest that a 2 month interval between the first and second injections results in higher levels of serum antibody than a 1-month interval. PMID- 3112730 TI - [Incidence and clinical characteristics of non-A, non-B viral hepatitis]. PMID- 3112733 TI - [Intra-arterial digital subtraction angiography with carbon dioxide]. PMID- 3112734 TI - Models for long-term care. PMID- 3112732 TI - Effects of air constituents on thermosensitivities of preoptic neurons: hypoxia versus hypercapnia. AB - The effects of hypoxia (10% O2) on the thermosensitivities of preoptic neurons were studied in urethanized rats and compared to the effects of hypercapnia (10% CO2). This was examined by regression of neuronal activity on preoptic temperature. During hypoxia, the slope of the regression line increased significantly in 8 (23%) of 35 warm-sensitive neurons and decreased in eight other neurons (P less than 0.05). During hypercapnia, the slope of the regression line decreased significantly in 7 (30%) of the 23 warm-sensitive neurons (P less than 0.05). No neuron was found that significantly increased the slope of the regression line. The effects of hypoxia on thermosensitivities (i.e. the slope of the regression line) of PO neurons differed from those of hypercapnia in chi square analysis (P less than 0.05). Responses of the cold-sensitive neurons to hypoxia or hypercapnia did not generally differ from those of the warm-sensitive neurons. During hypoxia and hypercapnia, arterial blood pressure, respiratory frequency, heart rate, and EEG were recorded to examine their relations to neuronal activity. The present results indicate that the thermosensitivities of preoptic neurons are modified by both hypoxia and hypercapnia, but that hypoxic differ from hypercapnic effects. PMID- 3112731 TI - [Carbonic anhydrase II deficiency: osteopetrosis, renal tubular acidosis and intracranial calcifications. Review of the literature and 3 cases]. AB - Three children in two unrelated families are affected by carbonic anhydrase II (CA II) deficiency. This disease has been reported in 27 other patients to date; the study of the pedigrees indicates that it is supported by autosomal recessive inheritance. All the patients have a very high CA I/CA II ratio (greater than 10(4) versus 6 to 10 in controls) and carrier detection is possible in obligate heterozygotes (CA I/CA II = 12 to 17). The clinical presentation consists in renal tubular acidosis, osteopetrosis and cerebral calcifications. The long term follow-up of these patients shows that the prognosis is mainly of neurological and mental expression. PMID- 3112736 TI - Private practice for older adults. PMID- 3112735 TI - Models for long-term care: health maintenance organizations. PMID- 3112737 TI - Home health care. PMID- 3112738 TI - Combined models--an intraagency. PMID- 3112739 TI - The role of advocacy organizations. PMID- 3112740 TI - Models for long-term care: ethical issues. PMID- 3112741 TI - Continuing education for practitioners. PMID- 3112742 TI - The geriatric imperative: entry-level and graduate nursing education. PMID- 3112743 TI - Nucleotide sequences of variable region segments of the immunoglobulin heavy chain of Xenopus laevis. PMID- 3112744 TI - The nucleotide sequence of the gene coding for diphtheria toxoid CRM176. PMID- 3112745 TI - Institutionalisation. Private lives. PMID- 3112746 TI - Role of diet in upper aerodigestive tract cancers. AB - A case-control interview study for assessing the role of dietary factors in selected cancers was undertaken in a hospital. Male patients from one community, with cancers of the oral cavity (n = 278), pharynx (n = 225), esophagus (n = 236), and larynx (n = 80) formed the case group. Patients diagnosed as not having cancer (n = 215) formed one control group, and a comparable sample of individuals from the general population (n = 177) formed another control group. All risks were adjusted for subjects' ages and habits of chewing and/or smoking tobacco, which are the two most important risk factors for cancers at these sites. A protective effect was observed with the intake of vegetables (twofold risk in nondaily vs. daily consumers) and fish (two- to threefold risk in those who did not eat at least once a week vs. those who did), and to a certain extent with pulses and buttermilk, in comparison with either one or both control groups. Intake of vegetables and fish were also observed to be risk modifiers for those who chewed and/or smoked tobacco. Lower levels of fat consumption was associated with elevated risk levels. The use of red chili powder emerged as a risk factor for all sites (two- to threefold risk with a dose-response relationship) compared with population controls. Tea drinking was also observed to be a risk factor for esophageal cancers, and to a lesser extent, for pharyngeal cancers. PMID- 3112747 TI - Reduced aflatoxicosis in livers of hamsters fed a manganese sulfate supplement. AB - Male, weanling Syrian hamsters (Mesocricetus auratus) were given (for 10 weeks) diets supplemented with manganese sulfate, aflatoxin, or a combination of both. All animals were killed and a histopathologic evaluation was performed on each liver to assess the influence of a manganese-supplemented diet on aflatoxicosis. Serum cholesterol and liver glycogen levels were also analyzed to further study the interaction of manganese and aflatoxin. Characteristic aflatoxin-induced precancerous histopathologic changes were observed in animals receiving the toxin. These changes included bile duct cell hyperplasia, enlarged nuclei, nuclear inclusions, and megala-hepatocytes. The dietary manganese addition to aflatoxin animals caused a slight reduction in the bile duct cell hyperplasia and significantly reduced the enlarged nuclei and nuclear inclusions. The latter indicates that the manganese may be influencing membrane chemistry. Animals receiving aflatoxin alone showed significantly increased serum cholesterol and liver glycogen. The cholesterol levels were significantly increased over the aflatoxin-induced levels when manganese was given in combination with the aflatoxin. The manganese lowered the increased liver glycogen levels caused by the aflatoxin. Dietary manganese shows some potential in suppressing several, but not all, of the aspects of developing aflatoxicosis in the hamster. The specific mode and site of action of manganese requires additional study. PMID- 3112749 TI - Clinical evaluation of pulpotomies with ZOE as the vehicle for glutaraldehyde. PMID- 3112748 TI - Weight change and peptide hormone responses in patients receiving interferon. AB - The purpose of this pilot study was to describe body weight status and peptide hormone responses in patients receiving interferon (IFN) therapy for renal cell carcinoma. Eighteen patients were on therapy for approximately two to three months. Mean weight loss of the patients was 2.2 +/- 0.9 kg (mean +/- SEM) or 4.9 +/- 0.9% of prestudy weight. Of the 18 patients, 6 were further evaluated for peptide hormone responses to meal stimulation before and after treatment (mean: 1.5 months). These subjects had a mean weight loss of 4.3 +/- 1.6 kg or 7.0 +/- 3.5% of prestudy weight. Blood was drawn from subjects before and six times after they had consumed a defined formula liquid meal to provoke enteroinsular peptide release. It was discovered that one-half of this group (n = 3; Group A) had some glucose intolerance following IFN therapy, despite increased response of insulin, gastric inhibitory polypeptide (GIP), and pancreatic polypeptide (PP) to meal stimulation. Further, patients in Group A had a weight loss of -11.7 +/- 2.7% of prestudy weight, whereas the other three patients (Group B) experienced a mean loss of -2.3 +/- 1.2% (p less than 0.04). The three subjects characterized by the smaller loss of prestudy weight (Group B) had decreased glucose response to meal stimulation, despite decreased responses of insulin and GIP. Response of PP was slightly increased with treatment in group B, but the increase was not as large as that in Group A. These data may suggest that extreme weight loss and altered peptide hormone response occur in a subset of cancer patients receiving interferon therapy. PMID- 3112750 TI - A novel model for testing enhancers of pigmentation. AB - Mouse skin, unlike human skin, does not contain active epidermal melanocytes, with the exception of the ear and tail skin in some pigmented strains. We have investigated enhancement of pigmentation in inbred C3H- mice using tail skin as a model for testing the effects of phosphorylated DOPA (DP) and ultraviolet radiation. Mice were restrained by cage dividers and treated with various doses of DP in dimethylsulphoxide (DMSO) or DMSO alone with or without the addition of UV radiation. Each tail served as its own control since only the dorsal surface was treated and irradiated. Pigmentation was graded blindly on histologic sections stained with Fontana-Masson. UV radiation caused a marked increase in epidermal and dermal pigmentation and this was enhanced in a dose-dependent manner by DP. However, there was minimal effect from DP alone. PMID- 3112751 TI - [Proteolytic activity of gastric juice in chronic pancreatitis]. PMID- 3112752 TI - [Waldenstrom's macroglobulinemia in a man with progressive hemiatrophy]. PMID- 3112753 TI - Pneumonias acquired from others. 2. Radiographic findings, treatment. AB - Although patterns found on the chest film of a patient suspected to have pneumonia are usually nonspecific by themselves, they are useful in eliminating or narrowing diagnostic possibilities. For example, a miliary pattern suggests miliary tuberculosis, but it may also be caused by several noninfectious diseases (table 1). Other clues, such as the presence or absence of fever, must also be considered to arrive at a likely diagnosis. Cavitary lesions, bilateral hilar adenopathy, pleural effusions, and pulmonary nodules are other findings that are commonly seen on the chest film of these patients. Possible infectious and noninfectious causes are listed in tables 2 through 5. Antimicrobial therapy that is appropriate, free from side effects, and cost-effective must be chosen. The frequency of administration of a drug can make a great difference in the total cost of treatment, since hospitals charge for each intravenous dose. The clinician should consider which drug is effective against the infective organism and also the least expensive to administer (table 6). PMID- 3112754 TI - Toward optimal use of radiographs. Should admission and preoperative chest films be routine? PMID- 3112755 TI - Association of Marek's disease with Ea-B and immune response genes in subline and F2 populations of the Iowa State S1 Leghorn line. AB - Chickens from the Iowa State S1 White Leghorn line, selected for characteristics of Ea-B serotype, humoral immune response to glutamic acid-alanine-tyrosine (Ir GAT), and response to Rous sarcoma virus (RSV)-induced tumors, were evaluated for genetic resistance to Marek's disease (MD). In the first two trials, sublines that were triple homozygous for the three traits were challenged with MD virus. Birds of the B1B1 blood type were significantly (P less than .001) more resistant to MD than chickens of the B19B19 blood type. High responders to GAT were significantly (P less than .001) more resistant to MD virus than low responders. The RSV classification had no detectable association with MD resistance. Chickens challenged with MD virus in the third trial were an F2 population produced from inter se matings of S1 chickens heterozygous for the three traits under selection. Data from this trial confirmed increased MD resistance of chickens possessing the B1B1 blood type when associated with genes encoding high immune response to GAT. PMID- 3112756 TI - Efficacies of mixtures of disinfectants and insecticides. AB - Efficacies of mixtures of diluted commercial formulations of selected insecticides and disinfectants were evaluated. Insecticides tested included representative pyrethroids (fenvalerate [Ectrin WDL and WD] and permethrin [Ectiban EC]), organophosphates (dichlorvos [Vapona EC], tetrachlorvinphos [Rabon WP] and dichlorvos/tetrachlorvinphos [RaVap EC], and a carbamate (carbaryl [Sevin S]). Disinfectants tested included representatives of cresylic acid (Biolene), cresylic acid/phenol (BioGuard X-185), phenol (1-Stroke Environ), quaternary ammonium (BioGuard S-3 and PFP-4), quaternary ammonium/formalin (DC & R), and formalin classes of disinfectants. Mixtures were tested for toxicity to two target insects (Musca domestica on plywood, Alphitobius diaperinus in litter) and two bacteria (Pseudomonas aeruginosa and Staphylococcus aureus). Of 56 mixtures evaluated, 24 showed reduced insecticidal toxicity and 35 showed reduced bactericidal activity compared with insecticides or disinfectants alone. PMID- 3112757 TI - DRG ripple effects on community health nursing. PMID- 3112758 TI - Mechanisms underlying the dietary fat impact on lipoproteins, atherogenesis and gallstones. PMID- 3112759 TI - Analysis of macrophages, activated cells and T cell subsets in inflammatory myopathies using monoclonal antibodies. AB - The availability of monoclonal antibodies which react with lymphocytes and cells of the MPS permits the construction of panels of reagents for immunophenotypic analysis of infiltrating cells in IM. We used immunohistochemical methods to immunophenotype inflammatory cells in muscle biopsies of patients with PM, DM and IBM. The cases of PM and IBM contained an intense MPS cell infiltrate in perivascular and endomysial areas, closely surrounding muscle fibers and occasionally included within the muscle fiber itself; an infiltrate of Leu-6+ cells with a morphology consistent with MPS cells in perivascular and endomysial distribution and occasionally closely apposed to muscle fiber membranes; lymphocytes and MPS cells expressing the IL2-R, and approximately equal numbers of T cells of helper-inducer and suppressor-cytotoxic phenotypes. DM cases had fewer MPS cells and relatively more B cells than T cells. PMID- 3112760 TI - [Studies with the Bactec 460 system. 2. Isolation of Mycobacterium tuberculosis from the sputum. Comparison of the radiometric with the conventional method]. PMID- 3112761 TI - Asymmetrical transfer of alpha-aminoisobutyric acid (AIB), leucine and lysine across the in vitro perfused human placenta. AB - The mechanism for establishing transplacental gradients for leucine, lysine and alpha-aminoisobutyric acid (AIB) has been investigated in the perfused human placenta. Experiments were done with either the maternal or the fetal circulation closed and the donor circulation open. Transfer of the amino acids towards the fetal side was more rapid than it was in the reverse direction. When the maternal perfusate was recirculated, the amino acid concentrations were maintained at a considerably lower level in the maternal circulation than in the open fetal circuit. When the fetal circuit was closed, the concentrations approached or slightly exceeded those in the maternal perfusate over a period of three hours. Within the placenta, higher concentrations were established during the experiments with transfer towards the fetal side than in the reverse direction. Of the three amino acids, leucine was transferred most rapidly across the placenta while AIB reached the highest concentrations in the placental tissue. The asymmetry of the transplacental amino acid flux is favoured by rapid uptake from the maternal circulation and transfer towards the fetus. Both rates exceed those observed in the reverse direction. The transfer rate of D-leucine was 1.7 times that of L-glucose. For in vitro studies of the transfer rate of physiological compounds a correction for diffusion is required. The results may differ considerably depending on which marker is used as the basis. PMID- 3112762 TI - [Isolation of a highly active preparation of beta-D-galactosidase]. AB - Methods for isolation and purification of beta-galactosidase from Bacillus subtilis, st. IBP-101 are described. The bacterial cells were disrupted by different procedures such as freezing and thawing with subsequent autolysis at 37 degrees C, disrupting in a French press DKM-3 or in ultrasonic disintegrators UZDN-1 (USSR) and Soniprep-150. It is shown that the specific activity and yield of the enzyme depends to a great extent on the disrupting procedure used. The best results were obtained in case of sonication. The preparation was purified by precipitation with ammonium sulphate (25-75% saturated) and chromatography on DEAE-cellulose and DEAE-Sephadex. The purified enzyme had a specific activity of 3155 units per mg protein. The molecular weight of the homogeneous according to gel polyacrylamide electrophoresis preparation was 215,000, as estimated by gel filtration, and 105,000, as estimated by SDS gel electrophoresis. The enzyme retains the activity in the presence of Na+, Mn2+ or Mg2+ ions or the thiolic reagents, dithiothreitol or 2-mercaptoethanol. The pH optimum of the enzyme activity is 6.3 and it is stable in water solutions at pH from 6 to 9 and can be lyophilized. The given preparation of beta-galactosidase has a high affinity for synthetic substrates such as o- and p-nitrophenyl-beta-D-galactopyranosides and 4 methylumbelliferyl-beta-D-galactopyranoside. PMID- 3112763 TI - [Purification of alkaline proteinase from Bacillus subtilis 72 using ion-exchange chromatography]. AB - Alkaline proteinase was isolated from the culture fluid filtrate obtained as a result of cultivation of Bacillus subtilis st. 72 using ion-exchange chromatography on a modified silochrome. Sorption of the enzyme at pH 6.0-6.3 and desorption at pH 7.5-7.8 followed by ultrafiltration through the membrane UAM-150 (USSR) resulted in a 5-fold increase of the enzyme specific activity calculated in respect of protein and an activity yield of 84%. PMID- 3112764 TI - [Effect of pesticides on bacterial membranes]. AB - The effect of pure preparation of ordram, fosalon, DDT, methoxychlorine, hydrel, dihydrel, 2,4-D, 2M-4C and of technical preparations of saturn, linuron, ronstar and keltan on the membrane functions (respiration and motility) of Azospirillum brasilense and Chromatium minutissimum cells and on malate and NADH oxidation by the isolated membranes of Micrococcus lysodeikticus was investigated. The effect varied from irreversible impairment to undetectable impairment of the measured activities depending on the type of bacteria and on the chemical used. The ordram induced permeability of the A. brasilense membranes without inhibition of the respiratory chain activity and selective inhibition of malate oxidase accompanied by stimulation of NADH oxidation in the M. lysodeikticus membranes indicates a possibility of ordram application as a regulator of bacterial metabolism. PMID- 3112765 TI - [67Ga scintigraphy in sarcoidosis]. PMID- 3112766 TI - [Early diagnosis of tuberculous eye diseases]. PMID- 3112767 TI - Cytostatic effect of DL-alpha-difluoromethylornithine against Plasmodium falciparum and its reversal by diamines and spermidine. AB - DL-alpha-difluoromethylornithine (DFMO) inhibited ornithine decarboxylase (ODC) activity and arrested the growth of Plasmodium falciparum at the early trophozoite stage. The inhibition of ODC activity did not result in the formation of an alternative diamine such as cadaverine. When putrescine or spermidine were added to the parasites grown in culture, the arrest was reversed, and normal schizogony was completed even in the presence of DFMO. Some reversal of the inhibition was achieved with cadaverine at high concentrations, while 1,3 diaminopropane and spermine failed to restore the development. Resumption of growth could be detected when putrescine was added even after 67 h of DFMO treatment. Electron microscopy did not reveal any changes in the morphology of parasites treated for 47 h, while 73 h of treatment with DFMO induced massive accumulation of pigment. Death was observed a few hours later. These results suggest that DFMO acts as a cytostatic rather than as a cytocidal agent. The four carbon diamine restored cell growth while the shorter or the longer homologous compounds showed little activity. PMID- 3112768 TI - Effect of praziquantel on certain immune responses of schistosomal Egyptian patients. I. Changes of specific immunoglobulins. AB - Specific antischistosomal IgG, IgM, and IgE were estimated by ELISA in 117 rural school students before specific treatment with praziquantel monthly for 3-4 months thereafter. IgG and IgM were estimated as percentage of bound antibodies. IgE was estimated by avidin-biotin ELISA (AB-ELISA) as IU/ml using a panel of known IgE standards. Soluble surface Schistosoma mansoni adult worm antigen was used for all estimates. Total IgE was estimated in a smaller group by an ELISA kit. The percentage of specific IgE was calculated. A group of endemic controls (22 students) and non-endemic controls (17 cases) were included. Statistical analysis of results showed the specific immunoglobulins to be significantly reduced 2 months after treatment of the schistosomal cases. These reduced levels, however, were still significantly higher than those of controls. The presence of early hepatosplenomegaly and the co-existence of other parasites had no significant influence on the results. No correlation could be established between the levels of specific antischistosomal IgG, M and E and the intensity of infection. The significance of these results is discussed. PMID- 3112769 TI - Effect of praziquantel on certain immune responses of schistosomal Egyptian patients. II. Cell-mediated lymphoproliferative response. AB - The lymphoproliferative blastogenic responses to mitogens, PHA and Con A, and to schistosome-derived antigens. S. mansoni worm and egg, were tested in 35 schistosomal patients and 10 healthy controls. Of the former group, 18 patients had intestinal mansoniasis and 17 had mansoniasis with hepatosplenomegaly. The test was repeated 2 weeks and 1 and 2 months after treatment with praziquantel. The delayed intradermal test for schistosomiasis was performed on 25 of the schistosomal patients and was repeated 1 month after treatment. Statistical analysis of results of lymphoproliferative blastogenic responses showed no significant differences between the control and the two schistosomal groups in response to mitogens. The group with intestinal mansoniasis responded significantly to both schistosomal antigens, compared to the control and hepatosplenic groups. Their proliferative responses showed a significant rise 2 weeks after treatment, then a gradual drop at 1 and 2 month intervals. The hepatosplenic group responded significantly to worm antigen before treatment; their proliferative responses to both schistosomal antigens showed a significant rise 2 weeks after treatment and remained raised thereafter. No relationship was established between either of the two schistosomal groups for age, intensity of infection or positive delayed intradermal reaction. PMID- 3112770 TI - Angiostrongylus cantonensis: immunoblot analysis of the antigens recognized by rats. AB - Following infection of rats with Angiostrongylus cantonensis, occurrence of anti parasite antibody in the serum was determined with special reference to the antigens recognized by host IgG antibodies, using SDS-PAGE combined with an immunoblotting technique. Three saline extracts of digestive organ, reproductive organ and body wall, isolated from adult female A. cantonensis, were used as crude antigenic solutions. Then 7 to 49 days after infection, IgG antibodies directed predominantly against a single antigen, referred to as Ac-1 antigen, were detected. After 91 days or more, infected rats formed antibodies not only against the Ac-1 antigen, but also against a wide variety of other components with molecular weights in the range of 26,000-220,000 dalton. By using an antiserum against Ac-1 antigen as a probe, it was shown that the molecular weight and subunit structure, as well as the immunoelectrophoretic mobility, varied according to the organ from which the antigenic extract was prepared. The Ac-1 protein in the extract of the reproductive organ, one of the major sources of the Ac-1 antigen, showed the same electrophoretic mobility as alpha-globulin. It has a molecular weight in the range of 100,000-200,000 dalton under both non-reducing and reducing conditions. Immunohistochemical studies, using the same antiserum and sectioned adult female worms, found Ac-1 antigen in the cytoplasm of oocytes at different stages of development, and in the lateral cord. PMID- 3112771 TI - A cryptic proofreading 3'----5' exonuclease associated with the polymerase subunit of the DNA polymerase-primase from Drosophila melanogaster. AB - The DNA polymerase-primase from Drosophila lacks 3'----5' exonuclease activity. However, a potent exonuclease can be detected after separating the 182-kDa polymerase subunit from the other three subunits of the enzyme (73, 60, and 50 kDa) by glycerol gradient sedimentation in the presence of 50% ethylene glycol. The exonuclease activity cosediments with the polymerase subunit, suggesting that the two activities reside in the same polypeptide. The 3'----5' exonuclease excises mismatched bases at the 3' termini of primed synthetic and natural DNA templates. Excision of a mispaired base at the 3' terminus occurs at a 10-fold greater rate than excision of the correctly paired base. When replication fidelity is measured by the bacteriophage phi X174 am3 reversion assay, the isolated polymerase subunit is at least 100-fold more accurate than either the intact polymerase-primase or a complex of the 182- and 73-kDa subunits. These results suggest that the 3'----5' exonuclease functions as a proofreading enzyme during Drosophila DNA replication in vitro and very likely in vivo. PMID- 3112772 TI - Cloning and expression of recombinant, functional ricin B chain. AB - The cDNA encoding the B chain of the plant toxin ricin has been cloned and expressed in monkey kidney COS-M6 cells. The recombinant B chain was detected by labeling the transfected cells with [35S]methionine and [35S]-cysteine and demonstrating the secretion of a protein with a Mr of 30,000-32,000 that was not present in the medium of mock-transfected COS-M6 cells. This protein was specifically immunoprecipitated by an anti-ricin or anti-B-chain antibody and the amount of recombinant B chain secreted by the COS-M6 cells was determined by a radioimmunoassay. Virtually all of the recombinant B chain formed active ricin when mixed with native A chain; it could also bind to the galactose-containing glycoprotein asialofetuin as effectively as native B chain. These results indicate that the vast majority of recombinant B chains secreted into the medium of the COS-M6 cells retain biological function. PMID- 3112773 TI - Drosophila Kruppel gene product produced in a baculovirus expression system is a nuclear phosphoprotein that binds to DNA. AB - The product of the Drosophila segmentation gene Kruppel was produced in cultured insect cells using the baculovirus expression system. When a cloned Kruppel cDNA sequence was inserted into the viral genome downstream from the promoter of the polyhedrin gene, a polypeptide with an apparent molecular weight of approximately equal to 72,000 was observed in the nuclei of infected cells. Antibodies were raised against this protein and used to detect Kruppel in Drosophila embryos. Characterization of the Kruppel protein extracted from infected cells showed that it is tightly bound to the nucleus, it binds to calf thymus DNA-cellulose, and it is phosphorylated. These results support the hypothesis that Kruppel is a regulatory protein that acts by binding DNA. PMID- 3112774 TI - Analysis of the role of cysteine residues in isopenicillin N synthetase activity by site-directed mutagenesis. AB - The predicted amino acid sequences of isopenicillin N synthetase from both Cephalosporium acremonium and Penicillium chrysogenum have two cysteine residues in analogous positions (Cys-106 and Cys-255 in the C. acremonium numbering). To examine the role of these cysteine residues in the activity of the C. acremonium enzyme, we used site-directed in vitro mutagenesis to change these cysteine residues to serine residues. Mutation of Cys-255 reduces specific activity approximately equal to 50%, whereas mutation of Cys-106 or mutation of both Cys 106 and Cys-255 reduces specific activity about 97%. This suggests that the cysteines are important but not essential for IPNS activity. Alkylation of IPNS also almost completely inactivated the enzyme, but residual activity could have been due to incomplete alkylation. Atomic substitution via genetic manipulation in this case is a more accurate means of assessing the role of sulfhydryl moieties in enzyme activity. PMID- 3112775 TI - Reduced tyrosine kinase specific activity is associated with hypophosphorylation of pp60c-src in cells infected with avian erythroblastosis virus. AB - Avian erythroblastosis virus (AEV) is a replication-defective retrovirus that causes erythroblastosis and sarcomas in chickens and transforms immature erythroid cells and fibroblasts in culture. AEV encodes two oncogenes, v-erbA and v-erbB, whose products are closely related to the thyroxine receptor and the epidermal growth factor receptor, respectively. Since tyrosine protein kinases have been implicated in the process of normal growth signal transduction, we wished to study the possible consequences of the expression of these mutated, growth-regulating receptor genes on the activity of the cellular tyrosine kinase pp60c-src. A continuous cell line from AEV-infected quail embryo fibroblasts was derived that exhibited a typical transformed phenotype and expressed the viral oncogene products, p75gag-erbA and gp66-68erbB. Using an immune-complex kinase assay, we found that the specific activity of pp60c-src in AEV-transformed quail cells was decreased by a factor of 6-30 relative to that found in uninfected quail cells. A concomitant 50-80% reduction of 32Pi incorporation into the pp60c src protein from radiolabeled, transformed cells was also observed, indicating a relationship between hypophosphorylation and diminished enzyme activity. Partial proteolytic phosphopeptide analysis revealed a decrease in phosphorylation of both serine- and tyrosine-containing peptides, suggesting an activation of specific phosphatases or inhibition of specific kinases in the AEV-transformed quail cells. Similar results were found in pp60c-src precipitated from AEV transformed chicken and rat cells. PMID- 3112776 TI - Introduction of v-Ha-ras oncogene induces differentiation of cultured human medullary thyroid carcinoma cells. AB - Medullary thyroid carcinoma (MTC) is an endocrine tumor of the thyroid C cells that expresses high levels of the neuroendocrine peptide hormone calcitonin. During tumor progression in the host, there is an apparent loss of differentiation in MTC cells that involves a consistent decrease in calcitonin content of the tumor cells associated with decreased expression of the calcitonin gene and/or changes in a mRNA alternative-processing pattern away from that characteristic of the parent thyroid C cell. We now report that introduction of the viral Harvey ras (v-Ha-ras) oncogene into cultured human MTC cells can reverse such changes in gene expression and can induce endocrine differentiation of the tumor cells. The expression of v-Ha-ras is associated with decreased cellular proliferation and DNA synthesis. There is a marked increase in the number of cytoplasmic secretory granules that are a classic feature of differentiated thyroid C cells. v-Ha-ras expression induces increased expression of the calcitonin gene and the processing of the primary gene transcript is shifted to favor calcitonin mRNA rather than calcitonin-gene-related peptide (CGRP) mRNA production. These studies with cultured human MTC cells provide a model system to study the role of Ha-ras and related genes in neuroendocrine differentiation. The findings suggest an important approach for identifying genes in solid tumors whose altered expression may play a role in the impaired maturational capacity characteristic of cancer cells during tumor progression. PMID- 3112777 TI - Antithymocyte globulin stimulates human hematopoietic progenitor cells. AB - Antithymocyte globulin (ATG), a horse antihuman thymus antiserum highly effective in the majority of patients with aplastic anemia, was studied for its in vitro effects on hematopoietic progenitor cells. Marrow cells isolated by an immunoadherence technique with the HPCA-1 (human progenitor cell antigen) monoclonal antibody after removal of contaminating T cells and macrophages formed erythroid colonies in methyl cellulose media in the presence of ATG at concentrations of 25-50 micrograms/ml. ATG also stimulated continuous production of hemoglobin-containing erythroid colonies beyond 35 days of culture when it was added to the culture weekly. ATG also had an indirect effect on myeloid (granulocytic and macrophagic) colony growth in vitro. At a concentration of 10 micrograms/ml, ATG stimulated late but not early myeloid progenitor cells to form mature colonies. This effect required the participation of lymphocytes containing the Leu-11 antigen and macrophages or supernatant fluids made from these two types of cells that had been preincubated with ATG for 3 hr and then cultured for 5 additional days. The supernatant fluids produced in such a manner showed characteristics similar to granulocyte colony-stimulating factor and had an activity peak that eluted at a volume corresponding to a 20,000 Da molecular mass protein by high-resolution liquid chromatography. PMID- 3112778 TI - Intracellular free calcium concentration measured with 19F NMR spectroscopy in intact ferret hearts. AB - Changes in the intracellular free Ca2+ concentration, [Ca2+]i, mediate excitation contraction coupling in the heart and contribute to cellular injury during ischemia and reperfusion. To study these processes directly, we measured [Ca2+]i in perfused ferret (Mustela putorius furo) hearts using 19F NMR spectroscopy to detect the 5,5'-difluoro derivative of the Ca2+ chelator 1,2-bis(o aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). To load cells, hearts were perfused with the acetoxymethyl ester derivative of 5,5'-F2-BAPTA. We measured 19F NMR spectra and left ventricular pressure simultaneously, at rest and during pacing at various external Ca concentrations [( Ca]o). Although contractile force was attenuated by the Ca2+ buffering properties of 5,5'-F2 BAPTA, the decrease in pressure could be overcome by raising [Ca]o. Our mean value of 104 nM for [Ca2+]i at rest in the perfused heart agrees well with previous measurements in isolated ventricular muscle. During pacing at 0.6-4 Hz, time-averaged [Ca2+]i increased; the effect of pacing was augmented by increasing [Ca]o. [Ca2+]i more than tripled during 10-20 min of global ischemia, and returned toward control levels upon reperfusion. This approach promises to be particularly useful in investigating the physiology of intact hearts and the pathophysiology of alterations in the coronary circulation. PMID- 3112779 TI - Triiodothyronine improves the primary antibody response to sheep red blood cells in severely undernourished weanling mice. AB - Three experiments were conducted in which weanling mice were fed a nutritionally complete diet either ad libitum or in restricted quantities such that they lost about 30% of their initial weight over a 14-day period. In Experiments 1 and 2, half the animals from each group received dietary triiodothyronine (T3) supplements. In Experiment 3, food-intake-restricted mice were fed graded levels of potassium iodide. Malnutrition reduced the number of nucleated cells per spleen, the number of splenic IgG plaque-forming cells (PFC) per 10(6) cells, and the serum antibody titers against sheep red blood cells. T3 supplements increased antibody titers, the number of nucleated cells per spleen, and both IgM and IgG PFC per 10(6) spleen cells in malnourished mice, but had no effect on well nourished mice. The beneficial effect of T3 was not a result of improved protein, energy, or iodine status in the malnourished mice. PMID- 3112781 TI - Enzymology and molecular biology of carbonyl metabolism. Aldehyde dehydrogenase, aldo-keto reductase, and alcohol dehydrogenase. Proceedings of an international workshop. Espoo, Finland, June 14-16, 1986. PMID- 3112780 TI - Fever is not responsible for the elevated glucose kinetics in sepsis. AB - Previous studies have suggested that alterations in the classical neuroendocrine system may not be responsible for the increased glucose metabolism observed during hypermetabolic sepsis. The purpose of the present study was to determine whether inhibition of the cyclooxygenase pathway with indomethacin, which prevents the production of arachidonic acid metabolites by this pathway and the sepsis-induced increase in body temperature, would abolish the increases in glucose appearance (Ra), recycling, and hyperlactacidemia. Sepsis was induced in chronically catheterized conscious rats by multiple injections of live Escherichia coli via a subcutaneous catheter. Septic animals received iv injections of indomethacin (5 mg/kg) every 6-8 hr to block the cyclooxygenase pathway. Glucose kinetics were assessed in 24-hr fasted rats using a constant iv infusion of [6-3H]- and [U-14C]glucose. Treatment with indomethacin prevented the 1-2 degrees C increase in body temperature observed in septic animals. Septic rats exhibited an elevated plasma lactate concentration and increased rates of glucose appearance and recycling. The sepsis-induced alterations in these variables were not attenuated by indomethacin. These results suggest that neither elevated body temperature nor the generation of arachidonic acid metabolites of the cyclooxygenase pathway is responsible for increasing glucose production in hypermetabolic septic rats. PMID- 3112782 TI - Comparison of the active sites of aldose reductase and aldehyde reductase from chicken. PMID- 3112783 TI - Inhibition of aldehyde reductases. PMID- 3112784 TI - Aldose reductase, enzyme or artefact? PMID- 3112785 TI - Rapid purification of rat lens aldose reductase. PMID- 3112786 TI - Characterization of aldose reductase activities from human and animal sources by a sensitive fluorescence assay. PMID- 3112787 TI - Aldose reductases from human retina and bovine lens: dependence of inhibition upon the choice of enzyme substrate. PMID- 3112788 TI - Irreversible aldose reductase inhibitors. PMID- 3112789 TI - Quantitation by radioimmunoassay of aldose reductase (ALR2) in normal and diabetic rats. PMID- 3112790 TI - Pig lens aldose reductase: purification and preliminary X-ray diffraction study. Oligomerization of the enzyme. PMID- 3112791 TI - Oxidant injury of cultured cells: biochemical consequences. AB - The experimental results summarized here suggest a mechanism of oxidant induced cell injury which begins with the generation of DNA strand breaks. The mechanism of the generation of these breaks is currently under investigation. The presence of DNA strand breaks activates pADPr polymerase which causes the conversion of cellular NAD to pADPr and free nicotinamide. It is likely that low levels of NAD are associated with inhibition of glycolysis and thereby contribute to the oxidant-induced fall in cell ATP. Additional factors are likely to contribute to altered cell metabolism following oxidant injury. Hyslop has shown that the Vmax of a critical enzyme of the glycolytic pathway, glyceraldehyde-3-phosphate dehydrogenase, is decreased following exposure to oxidant. Finally, it is likely that the oxidative phosphorylation functions of the mitochondrial membrane may also be perturbed by oxidant injury. The extent to which these alterations in cell metabolism occur in vivo following exposure to oxidants may be of great importance to our understanding of acute inflammatory tissue injury. PMID- 3112792 TI - Activation of the pulmonary arachidonic acid system and its consequences for hemodynamics and fluid balance. AB - The pulmonary vasculature and perivascular tissue is able to generate arachidonic acid metabolites with strong effects on vascular tone and permeability. Stimulators of the pulmonary arachidonic acid metabolism, which represents a highly potent mediator system, are components of the classical cascade systems, bacterial toxins, hypoxia, and a variety of other physiological and non physiological factors. Upon excessive stimulation, the pulmonary circulation responds with vasoconstriction and extravasation. Since granulocytes are always involved, their contribution to the resulting vascular effects has to be considered. PMID- 3112793 TI - Effect of the nonsteroidal antiinflammatory agent BW755C in rat and sheep endotoxemia. PMID- 3112794 TI - Vascular perfusion of the ischemic small intestine. PMID- 3112795 TI - The use of scoring systems as prognostic parameter after surgery and trauma. PMID- 3112796 TI - Corticosteroids in the treatment of septic shock. PMID- 3112797 TI - Prediction of outcome in sepsis. PMID- 3112798 TI - Influence of parenteral nutrition on lung surfactant in the traumatized rat. PMID- 3112799 TI - Scoring systems and predictors of ARDS and MOF. PMID- 3112800 TI - Prognostic indices in septic shock. PMID- 3112801 TI - Can the outcome after trauma or sepsis be predicted from biochemical or hormonal parameters? AB - The severity of shock of 36 surgical ICU patients was classified using the Injury Severity Score (N = 20) and the Sepsis Score (N = 16). A great number of laboratory parameters were repeatedly determined on 5 days following the trauma or the onset of septic symptoms. Blood lactate, C-peptide, BUN, osmolality, and thyroid hormones were most closely related to the severity of the disease. This correlation was, however, less pronounced in the trauma than in the septic patients. Lactate and thyroid hormones showed a typical course in the non survivors and may therefore be valuable as prognostic indices. PMID- 3112802 TI - Sickle cell vaso-occlusion in an animal model; intravital microscopy and radionuclide imaging of selective sequestration of dense cells. AB - The impaired deformability and heterogeneity of erythrocytes in sickle cell disease endows them with abnormal microvascular flow dynamics. In the sickle cell exchange-transfused rat model, sickle cells exhibit lower volumetric flux and shear rates compared to normal (HbAA) or autologous rat cells. A subpopulation of dense sickle cells and irreversibly sickled cells show a propensity to induce occlusion at precapillary arterioles, residing at such sites for several seconds and causing local rheological disequilibrium. Radionuclide studies with indium 111 demonstrate preferential uptake of labeled HbSS cells in pulmonary microcirculation. These data are relevant to the factors that are involved in the initiation and propagatin of vaso-occlusion resulting in derangement of homeostasis in certain microvascular beds and perhaps painful crisis and selective organ injury. PMID- 3112803 TI - Susceptibility of diabetic rat aorta to self-deactivation during prostacyclin synthesis. AB - The ability of aortic rings to produce PGI2 markedly decreased in streptozotocin induced diabetic rats when compared with age-matched controls. Arachidonic acid dose-dependently stimulated the production of PGI2 both in normal and diabetic rat aorta during 5 min incubation. The deficiency in PGI2 production in diabetic rat aorta was temporarily corrected by the addition of 5-20 microM of arachidonic acid. However, when aortic rings were incubated over a period of 10 min in the presence of arachidonic acid, the ability of PGI2 production in diabetic rats markedly decreased. Repeated exposures of aortic rings to arachidonic acid also markedly reduced PGI2 production in diabetic rats. PGI2 production in diabetic rat aorta was inactivated more readily than in normal rat aorta by pre-incubation with t-butyl hydroperoxide. Phenol had a protective effect on incubation-induced inactivation of PGI2 generating activity in diabetic rat aorta. Serum markedly stimulated PGI2 synthesis in normal and diabetic rat aorta. The serum activity in diabetic rats was less potent than in normal rats. Melittin and dipyridamole were effective in stimulating PGI2 release from diabetic rat aorta. These results suggest that enzymes in the aorta involved in PGI2 synthesis from released arachidonic acid are susceptible to self-inactivation in diabetic rats during the metabolism of arachidonic acid. This may contribute to the defect of PGI2 synthesis in diabetic rat aorta in addition to the decreased availability of the substrate. PMID- 3112804 TI - The effect of PAF (platelet-activating factor) on experimental cardiac arrhythmias and its inhibition by substances influencing arachidonic acid metabolites. AB - Platelet-activating factor (PAF), 10(-11) mol decreased the threshold of ouabain induced arrhythmia in guinea-pigs. The thresholds inducing premature ventricular beats and ventricular flutter were statistically significantly decreased by 27.4% and 15.6%, respectively. BM 13.177 (30 mg/kg), a thromboxane receptor antagonizing substance, and esculetin (1.2 mg/kg), a lipoxygenase inhibitor, abolished this arrhythmogenic effect of PAF. Acetylsalicylic acid (10 mg/kg) showed only a tendency to inhibit the PAF effect. These results suggest that PAF could play a role in cardiac arrhythmias under special conditions and it supports the hypothesis that PAF action is mediated by the release of leukotrienes and thromboxane. PMID- 3112805 TI - The effect of diphenylamine derivatives on arachidonic acid metabolism in rat peritoneal macrophages. AB - The effect of diphenylamine derivatives such as diclofenac sodium, mefenamic acid and lobenzarit disodium on arachidonic acid metabolism in rat peritoneal macrophages was examined. Lobenzarit disodium has no effect on prostaglandin E2 production as measured by radioimmunoassay although two other diphenylamine derivatives have a potent inhibitory activity. Three diphenylamine derivatives have no effect on Ca2+ ionophore-stimulated release of radioactivity from (3H)arachidonic acid-labeled macrophages. HPLC analysis revealed that lobenzarit disodium had no effect on the synthesis of lipoxygenase products as observed in diclofenac sodium and mefenamic acid. It is concluded that lobenzarit disodium, although its fundamental chemical structure resembles diclofenac sodium and mefenamic acid, has no inhibitory activity on arachidonic acid metabolism, suggesting that immunomodulatory activities of lobenzarit disodium are manifested without interfering with arachidonic acid metabolism. PMID- 3112806 TI - An in vitro method for assay of hormone or agonist-stimulated lipase activity. AB - An assay for in vitro measurement of hormone or agonist-stimulated lipase activity, using exogenous prostaglandin synthetase as a trap for liberated arachidonic acid is described. Fifteen of twenty-six hormones and agonists previously tested in vivo, were tested in vitro and either stimulated or inhibited release of arachidonic acid parallel to their activity in vivo. Vasopressin stimulated the release of arachidonic acid in a linear, log-dose manner, from 10(-11) M to 10(-5) M. PMID- 3112807 TI - Peripheral prostaglandin metabolite levels in women undergoing therapeutic abortions in the first trimester with and without treatment with prostaglandin synthetase inhibitor. AB - The levels of 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 xi-cyclo prostaglandin E2 (bicyclo PGEM), 13,14-dihydro-15 keto-prostaglandin F2 alpha (PGFM) and prolactin were measured in four serial plasma samples collected from thirty women undergoing therapeutic abortions in the first trimester by a suction curettage procedure. Eleven of these women received a preoperative loading dose of sodium meclofenamate, a PG synthetase inhibitor, before the abortion procedure was started and the rest received this medication after the last blood samples were drawn. Prolactin levels increased significantly during the procedure. Sodium meclofenamate treatment had no effect on this increase. Bicyclo PGEM levels did not increase during the procedure in untreated or treated women, whereas PGFM levels increased but only in untreated women. The lack of increase in treated women apparently was not a treatment effect because PGFM levels in corresponding samples of untreated and treated women were similar. Treatment significantly reduced the bicyclo PGEM levels immediately after completion of the procedure as compared to untreated women. This differential PG response to treatment is unprecedented and may be due to sodium meclofenamate inhibition of PGE2 and not PGF2 alpha synthesis. Nevertheless, these data demonstrate that sodium meclofenamate treatment of patients undergoing first trimester therapeutic abortion to relieve pain involves selective suppression of PGE2 synthesis. PMID- 3112808 TI - Forebrain norepinephrine and neurobehavioral plasticity: neonatal 6 hydroxydopamine eliminates enriched-impoverished experience effects on maze performance. AB - Newborn male rats were depleted of forebrain norepinephrine (NE) by systemic 6 hydroxydopamine injection and then reared from 25 to 60 days under either isolated or enriched conditions. They were subsequently tested for acquisition of either the Lashley III maze or the Hebb-Williams maze problems. Isolated rearing impaired Lashley maze performance of the controls but not the 6-OHDA injected rats. Similarly, for the Hebb-Williams maze, the isolation-reared controls made more errors than their enriched-reared counterparts while no differences were observed between the isolated and enriched reared, 6-OHDA injected rats. These results are consistent with the hypothesis that forebrain NE is permissive to the deleterious behavioral consequences of restricted experience during maturation. PMID- 3112809 TI - Salicylate potentiates valproate-induced hyperammonemia in the rat. AB - Valproic acid is known to cause an increase in blood ammonia levels in humans at the usual clinical dose. In most patients, this increase is small and asymptomatic, but in some patients the increase is larger and is associated with encephalopathy. In this study, valproate also caused a small increase in blood ammonia level (from 50 to 83 mumol/l) in Wistar rats. Salicylate potentiated this increase in blood ammonia (greater than 210 mumol/l) when coadministered with valproate at a dose of salicylate which did not cause a significant increase when given alone. Other nonsteroidal anti-inflammatory drugs tested (ibuprofen and naproxen) did not potentiate valproate-induced hyperammonemia, and paracetamol actually appeared to decrease ammonia levels. The degree of hyperammonemia was dependent upon diet, and fasting decreased the level of hyperammonemia. In order to determine what component of the diet was responsible for this effect, protein, fat and carbohydrate were given by gavage, individually and also a mixture of the three. Only the mixture was able to increase the degree of hyperammonemia, even though the number of calories in the mixture and in each nutrient given individually was approximately the same. 2,4-Dinitrophenol, which like salicylate uncouples oxidative phosphorylation, potentiated valproate-induced hyperammonemia at a much lower dose than salicylate. Whether salicylate can potentiate hyperammonemia and lead to encephalopathy in some patients and therefore represents one of the risk factors for observed cases of valproate toxicity remains to be determined. Potentiation of hyperammonemia by salicylates is also consistent with the apparent association between salicylates and Reye's syndrome which is also characterized by hyperammonemia. PMID- 3112810 TI - Effect of inherent muscle length on isometric plantar flexion torque in healthy women. AB - This study investigated the relationship between inherent muscle length and torque production in 59 healthy women. We recorded nondominant ankle range-of motion values for each subject. These values were partitioned into quartiles for two knee positions. Women with "loose" plantar flexor muscles comprised the first quartile, and those with "tight" plantar flexor muscles the fourth quartile. Tight- and loose-muscle groups were established for the 0-degree (fully extended) and 90-degree (flexed) knee test positions for data analysis. Torque measurements were obtained using an isokinetic testing apparatus. We asked each subject to perform a maximal isometric (static) plantar flexion contraction at each of three ankle positions: 7 degrees of dorsiflexion (angle A), 0 degrees or neutral (angle B), and 30 degrees of plantar flexion (angle C). Data analysis was performed using an analysis of variance for repeated measures. Results indicated that torque produced by the tight-muscle groups was significantly greater than the torque produced by the loose-muscle groups at both knee positions (p less than .05). Additionally, the ankle ROM data obtained suggest normative data different from those currently prevalent in the literature. Findings of this study may prove valuable in the rehabilitation of ankle injuries and could be beneficial especially to physical therapists in understanding more about normal ankle function. PMID- 3112811 TI - Comparison of seven- and five-day physical therapy coverage in patients with acute orthopedic disorders. AB - This study evaluated the efficacy of seven- versus five-day physical therapy coverage in an acute care hospital setting by monitoring percentage of consecutive treatments, mean number of treatments per patient, and lengths of hospital stay (LOS) for 482 patients with acute orthopedic disorders. The Experimental Group (n = 276) received seven-day coverage; the Comparison Group (n = 206) received five-day coverage for four months. Results were analyzed for the group as a whole and by diagnostic categories. Experimental Group subjects received a higher percentage of consecutive treatments than the Comparison Group subjects (72% vs 42%). No difference was found between the groups for mean number of physical therapy treatments received per patient. The LOS was neither significantly different between the two groups as a whole nor for 9 of the 11 diagnostic categories. The results imply that providing consecutive physical therapy treatments through seven-day coverage without increasing the number of physical therapy treatments will not reduce the LOS for patients with acute orthopedic disorders. PMID- 3112812 TI - Intracellular transport of thialysine and selenalysine in CHO cells. AB - The intracellular transport of thialysine and selenalysine in CHO cells has been studied. Data have been obtained indicating that the two lysine analogs can be transported by both the cationic aminoacid transport system and by the L transport system. The affinity of the cationic aminoacid transport system is similar for the two lysine analogs but lower than that for lysine and the affinity of the L transport system for the two lysine analogs is lower than that for leucine. PMID- 3112813 TI - Immunological determinations in the cord serum and aspects of the neonatal adaptation. AB - We have determined the immunograms and the titers of anti-influenza antibody in the cord serum of 112 newborns. The immunologic parameters have been correlated with signs of adaptation in the immediate neonatal period. The immunograms showed an increase of the values of IgG and the presence of IgM and IgA in the cord serum, at levels according with the increase of the titer of anti-influenza antibodies. The presence of IgM and IgA in the cord serum at high levels is the expression of an active process of antibody synthesis in these foetuses as the consequence of an intrauterine infection. In our study, maternal influenza was implicated in the stimulation of the foetus immune system and in the alteration of neonatal adaptation. PMID- 3112814 TI - Aspects of tonus modulation in guinea pig tracheal muscle. AB - We have studied the tonus of the tracheal muscle (tracheal spiral) gathered from guinea pig and kept in Tyrode solution at 38 degrees C, continuously oxygenated. Tonus variations were recorded by a tension transducer on an xy recorder. After administration of histamine (H) in the organ bathroom, we observed an increase of tonus, with large spontaneous movements of the tracheal muscle. Blocking the beta adrenergic receptors with propranolol (Pr) suppressed the effect of adrenaline (Adr) but did not influence the effects of II and acetylcholine (Ach) The reaction to II was more diminished in the presence of fosfobion (ATP) in the organ bathroom. PMID- 3112815 TI - [Uterine rheography under normal physiological conditions and in gynecological pathology]. PMID- 3112816 TI - Rheographic vascular manifestations in some rare malignant hemopathies. AB - The present paper is dealing with cerebral irrigation aspects in three patients with vera polycythemia and 16 with Cooley's anaemia using the non-invasive rheoencephalographic method. The rheographic exploration was done with a 4 channel I.C.E. rheograph, being recorded on a B-channel Galileo multirecorder in parallel with the mathematical derivative of the wave and an EKG lead. The analysis of the rheographic parameter revealed that in patients with vera polycythemia there is an obvious venous stasis as well as important vasomotor tonus modifications induced by an affected blood viscosity. In patients with Cooley's anaemia, modifications in the cerebral irrigation are dominated by chronic anaemia; the latter causes chronic hypoxia of the whole body and a reduced cerebral irrigation due to a depressed cardiac volume and vasomotor tonus to the effect of hypothermia--explained through cerebral vascular self-regulation mechanisms. The investigated groups are interesting because their diseases are rare and severe; their cardiac performance was severely affected, with severe hemodynamic disturbances in the cerebral circulation, too. PMID- 3112817 TI - Metabolic investigations in persistent depressive states in the elderly. AB - In a group of 100 elderly patients with persistent depressive states, a series of investigations were carried out: hematologic, lipid, protein, energy metabolism hydroelectrolytic and acid-base balance, blood rheologic properties, immunologic, reactivity and certain humoral and regulation mechanisms. The results were compared with those obtained in two control groups, identical in number, the former in the third age without depressive states and the latter of healthy adults. The results were evaluated statistically. The results demonstrate that in depressive elderly subjects changes of the various parameters studied occur in the same direction as those in the group of elderly subjects without depression, but are far more accentuated. PMID- 3112818 TI - [Existing and potential relations between dietary lipids and the plasma membrane]. PMID- 3112819 TI - Characteristic features concerning the action of prostaglandin F2 alpha (PGF2 alpha) on the microvascular territories drained by truncus jugularis. AB - In dogs, PGF2 alpha injected into the Arteria facialis increases the local blood flow and microvascular permeability accompanied by an important increase of lymph and salivary flow. The results of our investigations allowed us to speculate that PGF2 alpha may be an important component of the regulatory mechanism underlying salivary secretion. PMID- 3112820 TI - Effects of lesions to the dorsal noradrenergic bundle on counterconditioning of punished barpressing. AB - The possible contribution of the dorsal noradrenergic bundle (DB) to the development of a simple form of counterconditioning (an associative mechanism leading to behavioural tolerance for stress) was assessed by comparison of the performance of animals with 6-hydroxydopamine-induced lesions of the DB to that of sham-operated (SH) animals. Animals engaging in barpressing for food reward on a random-interval (RI) 64 sec schedule were presented with a stimulus signalling the concurrent operation of an RI-64 sec schedule of response-contingent shock. In the control condition (punishment), shock and reward never occurred as a result of the same barpress. In the experimental condition (counterconditioning), the frequency of shock and reward were the same as for the punishment condition but the two events always occurred in succession, with food following shock, as a consequence of the same barpress. DB lesions had no effect on the acquisition of rewarded barpressing or on the initial acquisition of the discrimination between the shock-free and shock-containing (signalled) components of the schedule. However, once performance on the discrimination had reached asymptote, DB animals in the punishment control group showed significantly less suppression to the signal than SH animals. The counterconditioning schedule used was effective, leading to significantly reduced response suppression in the SH animals in comparison to the SH group subjected to punishment. The pattern of findings in the DB groups was consistent with a blockade by the lesion of the development of counterconditioning. These results suggest, therefore, that the DB is involved in at least one associative mechanism leading to tolerance for stress. PMID- 3112821 TI - Structural plasmid instability in recombination- and repair-deficient strains of Bacillus subtilis. AB - Plasmid pGP1, containing a fusion between the penicillinase gene of Bacillus licheniformis and the beta-galactosidase gene of Escherichia coli, was constructed. This plasmid enabled a study of structural plasmid instability in Bacillus subtilis wild-type cells and a variety of B. subtilis strains, defective in recombination- and DNA-repair functions. Large differences with respect to the level of stability of this plasmid were observed in the various genetic backgrounds. PMID- 3112822 TI - Biological characteristics of interferon-r-induced resistant histiocytic lymphoma cell line U937. AB - A brief exposure (for 6 h) of U937 cells to interferon (IFN)-gamma (500 U/ml) followed by a long term incubation of cells in normal medium for 8 or more weeks resulted in the induction of cells that were refractory to the anticellular and differentiating effects of not only IFN-gamma but also IFN-alpha and IFN-beta at concentrations up to 10(4) U/ml. In addition, the cells became insensitive to the potent differentiating effect of the phorbol ester--tumor promoting agent (TPA). However, the resistant cells retained their sensitivity to the antiviral effect of different IFNs and were fullu responsive to the induction of endonuclease 2',5'-oligoadenylate (2-5A) synthetase by IFN. Furthermore, the resistant cell population appeared to be homogeneous because clones derived from single cells from this population all exhibited the same resistant phenotype to IFN and TPA. These results suggest that induction of resistant U937 cells may involve a dedifferentiation process which results in the formation of an immature cell population that do not respond to the differentiating and/or anticellular effects of various types of IFNs. PMID- 3112823 TI - The inhibitory effect of oral administration of garlic on experimental carcinogenesis in hamster buccal pouches by DMBA painting. AB - The inhibitory effect of oral administration of garlic on experimental carcinogenesis in buccal pouches induced by painting 9,10-dimethyl-1,2 benz(a)anthracene (DMBA) was studied on 40 golden Syrian hamsters. The animals were grouped at random into four experimental groups (oral administration of garlic, NTP, BP or mineral oil followed by DMBA painting on buccal pouches), three chemical control groups (oral administration of garlic, NTP or BP without DMBA painting) and a DMBA control group (only painted DMBA on buccal pouches). Starting from the fourth week after DMBA painting, the pouch mucosae were examined biweekly for its tumor formation and blood vessel architecture. Animals were sacrificed 25 weeks after DMBA application. Tumors and pouch mucosae were dissected to examine tumor nature and biochemical reactions of DNA synthesis and GGTase activity. The inhibitory efficacy of garlic, BP and NTP were evaluated according to the results of these examinations. Garlic was found to have a higher inhibitory efficacy than BP and NTP through the probable mechanism of competitive binding with nuclear DNA and diminishing the opportunity of DMBA to initiate carcinogenesis. Other factors related to cancer inhibition included insufficient local blood flow, low GGTase activity and lesser DNA synthesis. The inhibitory effect of fractions of garlic on experimental carcinogenesis should be a reasonable and necessary continuation in future studies of the series of cancer prevention by garlic. PMID- 3112825 TI - Transference: current concepts and controversies. AB - In this paper I have presented a brief outline of some of the more important issues regarding transference. To summarize I shall restate ten transference issues heretofore discussed: What should be included in the definition of transference? Should it be defined narrowly or broadly? In what ways can transference be usefully viewed in relation to reality? What merit is there in distinguishing the working alliance from transference? Should self and object transference be differentiated? Should transference neuroses be discriminated from transference reactions on the one hand and from transference psychoses on the other? In addition to sexual and aggressive transferences, should sexualized and aggressivitized transferences, respectively, be distinguished? How may transference be conceived of as a vehicle of cure and yet also as a resistance to cure? What is to be said for the relative merit of the "here and now" versus the "there and then?" What is the role of transference in relation to insight on the one hand and to the therapeutic object on the other? What are some of the basic issues in countertransference? PMID- 3112824 TI - [Valproic acid derivatives: toxicity and adverse effects]. PMID- 3112826 TI - Developmental approaches to the psychology of religion. PMID- 3112827 TI - Observations on the meeting between Allport and Freud. PMID- 3112828 TI - Parenting a damaged child: mourning, regression, and disappointment. AB - This paper is an examination of the long-term parenting experiences of parents who have given birth to CNS damaged infants. In particular, the focus is on the mourning, regression, rage, and depression that frequently attend these parents throughout their lives and can become pathological and pathogenic interferences with the provision of good-enough parenting. Several clinical vignettes were presented, each of which illustrated the usefulness of different psychoanalytic clinical theories about normality and pathology of parenting and parent-child interaction. The now-classical contribution of Solnit and Stark (Mourning and the Birth of a Defective Child, 1962) is reviewed along with Benedek's and others' psychoanalytic theories about normal parenting. The thinking of these writers is within the framework of structural/libidinal theory and seems to be useful in describing certain parenting problems that concern the mourning and regressive aspects of parenting. However, it was proposed that some of the adaptive coping and pathology encompassed by Solnit and Stark's explanations is not comfortably illuminated by the structural clinical theory of conflict and drives. Freud's discussion (1917) compares mourning and melancholia, which he differentiated as related but dynamically distinct clinical phenomena. This work is briefly recalled as an earlier point in theory building where structural theory was not sufficient to explain clinical depression and rage that exceeds normal mourning (as in Freud's melancholia). It is felt that an additional theoretical perspective on parenting provided by self psychology can fill in some of the gaps left by structural theory explanations. The self psychology perspective is particularly helpful with understanding the rage, ambivalence, and chronic depression often experienced by parents of damaged children. According to this perspective, the damaged child is a disappointing selfobject for the parent, and the parent's self organization will give him the resources to cope adaptively or to develop narcissistic pathology. Three types of intrapsychic problems for a parent are described: mourning the lost object, the fantasied perfect child; experiencing and recovering from regression to early identifications with his own parents; withstanding tension and regulating one's self (experiencing chronic depression and rage) when confronted with a great disappointment in a selfobject (represented by the damaged child). It is important when designing intervention strategies in a hospital or pediatric clinic setting to clarify which type of problem is the major focus of the parent's struggle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3112829 TI - Mother and child. A psychobiographical portrait of Mary Cassatt. AB - The noted American impressionist, Mary Cassatt is remembered for her intimate portrayal of women, children, and the mother-child relationship. In this paper I have attempted to highlight some of the psychological forces impinging upon the artist, feeling that the artist's work is highly overdetermined. Mention was made of some of the difficulties that a psychobiographical study engenders. Nevertheless, it is hoped that such a study leads to enhanced understanding and appreciation of the artist, her work, and her rich inner world. An examination of the artist's life indicates that difficulties in the family of origin impinged upon her and deeply influenced her work. The loss of several siblings during critical developmental subphases may have produced intense survival guilt in Mary, motivating her to "recreate" her siblings on canvas and to devote her life to care of survivors. Lack of confirmation of Mary's talents by her father may have hindered her development, propelling the child toward a profoundly libidinalized and enmeshed relationship with the mother. Mary's intense relationship with her mother may have led the artist to develop particular stylistic nuances in her productions, contributed to her inability to become a wife and mother herself, and led to frequent episodes of depression. A case was made that Mary suffered from narcissistic disturbance, never completing the recognition of herself as a person outside of the orbit of her mother. Finally, the role of Edgar Degas in the artist's life was described. He seems to have played a major role in the evolution of Mary's style as well as being an important influence in her making a partial separation from her mother in adulthood. In spite of Mary's deep personal suffering, she was able to epitomize in her paintings the most tender and nurturant of relationships. By painting the mother-child theme, she sublimated her own wishes to become a mother as creator of art. Within her family system, she appropriated the position of mother; as the artist, she became the interpreter of this experience. By developing her talent, she communicated her wish to be a mother, and expressed the need to find, if only on canvas, a more truly empathic mother. In essence, her work allowed her to conceive of a life different from the one external reality imposed upon her. It also served as an indispensable adaptive function, allowing the artist to communicate with others, achieve recognition, and play.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3112830 TI - From the analysis of an obsessive hummer: theoretical and clinical implications. PMID- 3112831 TI - Love, seduction, and trauma. PMID- 3112832 TI - The unanalyzable transference: a portrait of Roustang's critique of classical technique. PMID- 3112833 TI - Female bonding: some supportive findings for Melanie Klein's views. PMID- 3112834 TI - Immunization factors in development of the African personality: preliminary observations. PMID- 3112835 TI - The familial self, the individualized self, and the transcendent self: psychoanalytic reflections on India and America. PMID- 3112836 TI - Creativity and the constructing of the self. PMID- 3112837 TI - Roland Barthes: the text as self; the self as text. PMID- 3112838 TI - Psychoanalysis in the arena: how Freud fares in the Science Times. PMID- 3112839 TI - Longitudinal studies of biologic markers for depression in male anorectics. PMID- 3112840 TI - The changing challenges of women's health for society and the health care system. PMID- 3112841 TI - Advances in Indian health care. PMID- 3112842 TI - The organization of health services for Indian people. AB - The Indian Health Service (IHS) is a bureau of the Health Resources and Services Administration, an agency of the Public Health Service. It was formed in 1955 by a transfer of health services from the Bureau of Indian Affairs, Department of the Interior. Since that time, IHS has grown larger and more complicated and has become a truly complex national organization that is responsible for direct and contract health care services to approximately 1 million Indian people. The historical background of the Service, its present organization, and the services that it provides through a variety of organizational structures are outlined in this report. PMID- 3112843 TI - The Indian Health Service record of achievement. AB - The Indian Health Service (IHS) was transferred from the Department of Interior to the Public Health Service in the Department of Health, Education, and Welfare in 1955. At that time, the general health of Indian people substantially lagged behind the rest of the U.S. population. This gap was reflected in mortality rates which were several-fold higher for Indians, or reflected in time; there were decades between the dates when the U.S. population achieved certain lower death rates compared with the dates when similar reductions were achieved by Indians. As a result of preventive health programs, improvements in sanitation, and the development of a number of medical advances, substantial progress has been achieved in improving the health of American Indians and Alaska Natives. Life expectancy of Indians has increased 20 years between 1940 and 1980. From 1955 through 1982, the death rate for Indian infants dropped by 82 percent. Also, the age-adjusted death rate for tuberculosis decreased from 57.9 per 100,000 population in 1955 to 3.3 in 1983. These and other improvements are summarized in this paper. PMID- 3112844 TI - The Indian burden of illness and future health interventions. AB - This article describes the burden of illness of Indians eligible for services from the Indian Health Service (IHS) and discusses strategies for reducing morbidity and mortality related to those conditions. To improve health to an extent that parallels the IHS's past achievements, the illnesses that now are prevelant among Indians require changes in personal and community behavior rather than intensified medical services. Analysis of these conditions leads to the conclusion that much of the existing burden of illness can be reduced or eliminated. IHS is responding to this challenge by continuing to ensure Indians' access to comprehensive health care services, by increasing educational efforts aimed at prevention, and by enlisting the support of other government and private organizations in activities that have as their purpose treating diseases if intervention will lessen morbidity and mortality (such as diabetes and hypertension) and encouraging of dietary changes, cessation of smoking, exercise, reduction in alcohol consumption, and other healthy behavior. PMID- 3112845 TI - Using staff input to set priorities in an Indian Health Service clinic. AB - The McLaughlin Public Health Service clinic serves several thousand Lakota people (Sioux) on Standing Rock Indian Reservation, SD. In 1981, a priority-setting exercise established for the first time a grassroots expression of the concerns of the clinic's staff. A three-step process was used in which each staff member first compiled an open-ended list of health needs, then ranked the relative contribution of five factors to making these problems important, and assessed each problem listed by those factors. The factors used were mortality, morbidity, vulnerability to intervention, facilities on hand, and social implications. The resulting priority table represented each person's assessment of the health needs of the community. A composite table was created to represent the group's assessment. The staff concluded that among the many problems listed, alcoholism and diabetes were the most compelling health problems. The priority score was almost identical for each, but the reasons were different. Alcoholism was rated highly because it was felt to be widespread and had serious social implications. Diabetes was ranked highly because it was felt to be lethal and vulnerable to intervention. A significant long-term benefit to the clinic of the 3-month process was to stimulate consultation within the local clinic and to unify the health team, endowing the members with a common sense of purpose. PMID- 3112846 TI - Job achievements of Indian and non-Indian graduates in public health: how do they compare? AB - A graduate education program in public health for American Indians was introduced in the fall of 1971 at the College of Public Health, University of Oklahoma Health Sciences Center. The program was initiated with support from the Office of Economic Opportunity. Between August 1, 1971, and December 31, 1983, 52 American Indians received public health degrees from the University of Oklahoma's College of Public Health. Of that number, 50 received masters degrees in public health; 1 a PhD; and 1 a DrPH degree. Degrees were granted in these disciplines: biostatistics, epidemiology, environmental health, health administration, health education, and human ecology. This study assesses the job achievements of 51 of those American Indian graduates. Each Indian was paired with a non-Indian graduate randomly selected from a cluster sample compiled from the school's files of non-Indian graduates. The results of this study showed that Indian graduates had the kinds and amounts of responsibilities, with the exception of budget approval responsibility, that one would acquire or expect to acquire in a key administrative or staff position. The study further indicated that Indian graduates were generally achieving as much success and satisfaction in their jobs as the non-Indian graduates. PMID- 3112847 TI - An approach to the problem of teenage pregnancy. AB - Sex education continues to gain prominence as a critical factor in current challenges to the nation's public health. Adolescent pregnancy, with its frequently adverse consequences for the health and well-being of both mother and child, has reached unprecedented levels in the United States, and AIDS now threatens society in its entirety. Despite awareness that effective sex education is essential to combatting these problems, current debates, focused on the content and timing of sex education provided in the schools, are shortsighted. As currently practiced in this country, sex education curriculums convey the wrong message and are targeted to the wrong audience. In emphasizing the provision of data to youth, we ignore the fact that parental guidance and direction are more often helpful than data and options. Yet we fail to provide parents and others who comprise the traditional systems of child care and nurturance with the information they require to assume responsibility for the safe and healthy development of children and youth. Understanding the reasons for the failure of conventional sex education provides a foundation for developing a more effective approach to preventing adolescent pregnancy. Defining an effective message and targeting information to the appropriate audience are necessary to effect a significant reduction in premature sexual behavior among adolescents. PMID- 3112849 TI - The voluntary acceptance of HIV-antibody screening by intravenous drug users. AB - Intravenous drug abusers in a methadone program in Minnesota were offered HIV antibody screening to determine the degree of interest in screening and extent of infection. Thirty-nine (85 percent) were willing to be tested. Only seven refused. All patients were aware of acquired immunodeficiency syndrome (AIDS) and their high risk of exposure to the AIDS virus through sharing of injection paraphernalia. None reported exposure to additional risk factors, such as homosexual or bisexual activity or having received a blood transfusion. Of the patients tested, none was positive for HIV antibodies. The high degree of patient interest in screening was unanticipated as was the lack of positive laboratory findings for HIV antibodies. Factors associated with acceptance of testing included patient awareness of high seroprevalence rates, indifference to potential negative social consequences of positive HIV-antibody status, and the voluntary nature of the testing. These findings raise a cautious sense of optimism about HIV-antibody screening for similar risk groups. PMID- 3112848 TI - Review of death certificates to assess completeness of AIDS case reporting. AB - To assess the level of reporting of acquired immunodeficiency syndrome (AIDS) cases, the authors reviewed death certificates for periods of 3 months during July through December 1985 in each of four cities: Washington, DC, New York City, Boston, and Chicago. Since reporting began in 1981, these cities have reported 38 percent of all AIDS cases in the United States. Death certificates were selected and matched to the AIDS surveillance registries in each city, and medical records of those not on the AIDS registry were reviewed to determine if AIDS had been diagnosed. The estimated completeness of AIDS case reporting to AIDS surveillance systems was high in all four cities (ranging from 83 percent to 100 percent). The unreported cases were similar to reported cases with respect to sex, race, risk factor, and specific diagnosis. Of the causes of death examined, AIDS, Pneumocystis carinii pneumonia, and Kaposi's sarcoma were predictive of AIDS as defined by the CDC case definition. However, 77 of 588 deaths (13 percent) attributed to 1 of these 3 causes occurred in cases that were presumptively AIDS but did not meet the diagnostic requirements to be classified as AIDS for reporting purposes. A review of death certificates provides an easy and rapid means of evaluating surveillance efforts and can be a useful adjunct to other methods of surveillance for AIDS. PMID- 3112850 TI - Characteristics of drug abusers that discriminate needle-sharers. AB - To identify variables that discriminate needle-sharing among drug abusers, 224 male drug abusers were studied. They had been admitted to a 30-day inpatient drug treatment program over a 19-month period (September 1983 through March 1985). The variables examined were divided into three categories: demographic (age, race, education), personality (Minnesota Multiphasic Personality Inventory [MMPI] scores and MMPI deviant scores), and drug use patterns (drug of choice, use of single or multiple [mixed] drugs, severity of drug use, and place of use). Three variables were identified that discriminated needle-sharers from other drug abusers. Compared with other drug abusers, needle-sharers used more multiple drugs, were more likely to use a "shooting gallery," and had more problems related to drug use. No demographic or personality variables discriminated needle sharers from nonsharers. The data suggested that needle-sharing is widespread in the drug culture. Needle-sharing was not confined to a particular racial group, educational level, or personality type. These findings can be used to structure education programs about acquired immunodeficiency syndrome (AIDS) for drug abusers. Drug treatment programs appear to provide an important opportunity to educate drug abusers about AIDS and related health issues associated with needle sharing. PMID- 3112851 TI - Increased infant mortality in Jersey City. AB - The infant mortality rate for 1982 in Jersey City, a medium-sized urban community, was found to have increased sharply from that for 1981. An investigation by health officials revealed that the increase occurred only among infants delivered to Jersey City residents at a large local municipal hospital. An increase in the incidence of newborns with birth weights of 501-1,000 grams (g) and a decrease in their survival rate accounted for much of the increase. Although local increases in infant mortality are reported in the lay press, the articles usually lack any meaningful analyses. Furthermore, investigations of such increases have not been described in the medical literature. This report describes the investigation of the rise in infant mortality for Jersey City, demonstrates how local officials can approach the problem, and indicates how essential the availability of linked birth and infant death records are to the effort. PMID- 3112852 TI - Maternal exposure to neighborhood carbon monoxide and risk of low infant birth weight. AB - This case-control study investigated the potential association between ambient levels of carbon monoxide in a pregnant woman's neighborhood of residence and her chance of delivering a low birth weight infant. Low birth weight infants and normal birth weight infants were contrasted with respect to ambient levels of CO during the 3 months prior to delivery in the neighborhoods where their mothers lived at birth. After adjustment for the confounding effects of maternal race and education, there was no association between higher CO exposure and higher odds of low birth weight. These data do not support a strong association between maternal exposure to neighborhood CO during pregnancy and odds of delivering a low birth weight infant. Further investigation of the effects of CO exposure on birth weight, with direct measurement of total CO exposure, is needed. PMID- 3112853 TI - Use of a compliance index for community fluoridation. AB - Fluoridation of public water supplies is the best method of preventing dental caries. Yet, many water systems do not maintain the optimal concentration of fluoride. The Community Fluoridation Compliance Index was developed to provide retrospective and prospective information on water systems in complying with local and State standards. This index permits flexibility in the amounts of optimal fluoride concentration and the frequency of fluoride sample testing. In addition, the index can be modified to address the size of the population served by the water system. The index's components are reviewed, and its use is demonstrated on 50 water systems from Illinois and 50 from Ohio. Annual data from these two States show how this information can be used for targeting corrective action so that the population receives the greatest benefit from fluoridation. These findings suggest that the Community Fluoridation Compliance Index can be a useful administrative instrument for comparing relative compliance results. Further studies to determine its acceptance at the State and local levels are warranted. PMID- 3112854 TI - Marketing family planning services in New Orleans. AB - The health care profession is witnessing a shift in focus from the interests and needs of the service provider to those of the potential consumer in an effort to attract and maintain clients. This study illustrates the role that marketing research can play in the development of program strategies, even for relatively small organizations. The study was conducted for Planned Parenthood of Louisiana, a recently organized affiliate that began offering clinical services in May 1984, to provide information on the four Ps of marketing: product, price, place, and promotion. Data from telephone interviews among a random sample of 1,000 women 15 35 years old in New Orleans before the clinic opened confirmed that the need for family planning services was not entirely satisfied by existing service providers. Moreover, it indicated that clinic hours and the cost of services were in line with client interests. The most useful findings for developing the promotional strategy were the relatively low name recognition of Planned Parenthood and a higher-than-expected level of interest that young, low income blacks expressed in using the service. PMID- 3112855 TI - The impact of the addition of naloxone on the use and abuse of pentazocine. AB - An epidemic of abuse with "T's and blues" began in the late 1970's in which pentazocine-Talwin tablets ("T")--and the antihistamine tripelennamine (known as blues) were crushed, dissolved together, filtered, and injected intravenously. The resulting high was reported to be similar to that of heroin. In 1981, the manufacturer and the Food and Drug Administration met to discuss a possible solution. As a result, 0.5 mg of naloxone hydrochloride, a narcotic antagonist that is pharmacologically inactive at that dose orally but active if administered parenterally, was added to the tablet formulation. The reformulated product, Talwin Nx, was approved for marketing in late 1982 and introduced in the second quarter of 1983. Distribution of Talwin tablets in the United States was discontinued. The Drug Abuse Warning Network (DAWN) of the National Institute of Drug Abuse and IMS America's National Prescription Audit were used to review the use and abuse patterns of pentazocine before and after the naloxone intervention. The number of prescriptions dispensed quarterly for pentazocine products remained fairly stable from 1981 through the first quarter of 1983 and increased after the introduction of Talwin Nx. In contrast, DAWN emergency room and medical examiner mentions decreased after the product reformulation. The rates of both emergency room and medical examiner mentions per million prescriptions were substantially lower in the 2 years following the introduction of Talwin Nx (decreases of 70 percent by emergency rooms and 71 percent by medical examiners), indicating that the product reformulation successfully reduced pentazocine abuse. PMID- 3112856 TI - Inventory of surveys on smoking. AB - A review of surveys on smoking was undertaken by the Smoking, Tobacco, and Cancer Program of the National Cancer Institute as part of its planning for smoking control interventions. Eighteen surveys collecting smoking data were identified. The key persons associated with the surveys were interviewed according to a uniform protocol developed to obtain comparable data on the content, timeframe, population sample, methodology, availability of data, and mode of information dissemination of the surveys. Analysis indicated that the main variations among surveys occurred in the age range of the population sampled, the definition of smoking behavior, and the quantification of cigarettes smoked. Other issues of special interest compared in the surveys included type of cigarette smoked, attempts at smoking cessation, smokeless tobacco use, passive smoking, use of low tar and low nicotine cigarettes, and smoking among special populations (women, youth, Hispanics, and blacks). Two main areas of concern in planning, targeting, and evaluating timely and appropriate smoking behavior interventions are the lag between data collection and publication of survey results and the variability in the content and methodology of the surveys. PMID- 3112857 TI - Reported vague symptoms and at-risk status: the case of polyvinyl chloride workers in Louisville. AB - This study concerns the frequency of visits to the dispensary by workers with vague symptoms of physical illness at a polyvinyl chloride plant in Louisville, KY, where an outbreak of hepatic angiosarcoma occurred. The illness behavior of three cohorts of workers at three levels of risk--workers removed from the chemical plant to a pallet plant (PP) because their screening results indicated liver abnormalities; workers who had some positive test results (TP); and workers whose test results were negative (TN)--was studied before (time 1) and after (time 2) the angiosarcoma crisis. It was predicted that, during time 2, the groups' visits to the dispensary would increase in relation to their levels of risk (PP greater than TP greater than TN). Although there was an overall increase in the percentage of visits because of vague symptoms during time 2, the only cohort with different behavior was the group of TP workers: they reduced their use of the dispensary. These results are similar to those in a previous study in which all symptoms of illness were included. It is speculated that social and individual factors, as well as the labeling phenomenon, explain the results. Health care providers are encouraged to follow up with workers at risk who seem to avoid monitoring their health. PMID- 3112858 TI - Terminal care preferences: hospice placement and severity of disease. AB - National Hospice Study data for 1981-82 were used to predict the location of care for terminal cancer patients. Sites of care were conventional care in hospitals, hospital-based hospice care, and hospice care in the home. Subjects were terminal cancer patients with a prognosis of less than 6 months of life who were attended by a primary concerned person. There were 1,732 patients 18-99 years old-293 conventional care, 612 hospital-based hospice care, and 827 hospice home care patients. Data sources were the patient, the primary concerned person, the family, and the medical record. Data were obtained at initial interview for the study, 1-week followup, reassessment every 2 weeks, and bereavement interviews. Information was grouped in the following categories: patient functional status, patient psychological outlook, symptomatology, medical condition, and characteristics of the primary concerned person and family. Conclusions were reached by univariate and multivariate analysis. First, a progression of functional disability was found to exist among care sites, from hospice home care for the least disabled to hospital-based hospice care to conventional care for patients with the greatest disabilities. The location of care was best explained by the patient's functional capacity. Second, the location of care was found to be poorly explained by extent of organ involvement or specific symptoms. Third, the primary concerned persons of patients under hospice home care experienced more stress but reacted no differently when compared with primary concerned persons at other care sites. Fourth, patients under hospice home care survived the longest and reported greater family closeness than other care groups. PMID- 3112859 TI - Left ventricular function in adults with atrial septal defect. AB - Sixteen patients with secundum atrial defect were catheterized giving emphasis to the analysis of the left ventricle at end systole and mid-ejection. The mean ejection fraction of the group was subnormal 57 + 8% when compared with 30 normal patients (71 + 109) P less than .005. Eight patients showed elevated end diastolic volumes (156 + 10cc) when compared to our normal group (95% + 10cc) P less than .005. A total of 32 hypokinetic and 35 tardokinetic areas were found. Eight patients were restudied after nitroglycerin (0.4 mg sublingually) with an improvement in the ejection fraction from 54% to 70% (P less than .005) and normalization of most of the hypokinetic areas. No correlation was found between total ejection fraction or total systolic wall motion and the shunt size. Probably these left ventricular wall motion abnormalities are primary and not due to the shunt size. PMID- 3112860 TI - [Frequency of isolation and drug resistance of bacterial strains isolated from respiratory material in patients with cystic fibrosis]. AB - During 1985, 251 respiratory samples from 61 patients were examined at the tuscan cystic fibrosis Center (Florence), and isolated strains were tested against various antimicrobial drugs. Pseudomonas aeruginosa and Staphylococcus aureus were the predominant pathogens isolated. Infections caused by St. aureus were the commonest during the first years of life, whereas those caused by Ps. aeruginosa, occasional at early age, became chronic and the main source of infection with growth. Sensitivity testings against antibiotics confirmed that Ps. aeruginosa isolated from cystic fibrosis patients has a high percentage of resistant strains. The most active drugs were ceftazidime and aztreonam. An increased resistance to aminoglycosides was observed. PMID- 3112861 TI - [Clinical and laboratory study of 7 cases of lupus anticoagulant]. AB - The clinical and laboratory data from seven patients with "Lupus anticoagulant" are reported. Laboratory tests are reliable as far as identification and properties of this kind of anticoagulant are concerned. Clinically, it is dramatic how often these patients show thrombotic phenomena. Clinical or laboratory tests which could point out whether these patients are at risk of incurring into thrombotic or hemorrhagic phenomena are not available, which underlines the critical situation one has to confirm with in case a patient with "Lupus anticoagulant" has to undergo surgery. PMID- 3112862 TI - Regression of mediastinal Hodgkin disease after therapy: evaluation of time interval. AB - Ninety-one patients with Hodgkin disease of the upper torso who had mediastinal masses were studied to determine the frequency of residual mass and the time required for resolution or stabilization of the mass. In 72 of these patients, radiographs from sufficient intervals were available for determination of the rate of regression. In 62 patients (86%), the mediastinum returned to normal width within 11 months, regardless of the size of the mass. The mediastinum returned to normal in all but one patient with small masses. The intrathoracic relapse rate did not correlate with the regression time of the masses, but relapse occurred more than twice as often in patients with residual mediastinal widening. PMID- 3112863 TI - Esophageal carcinoma: modest benefits from combined modality therapy. AB - Between 1969 and 1986, 109 consecutive patients with esophageal carcinoma were studied. Of the 77 patients who had squamous cell carcinoma, 62 received definitive treatment for disease confined to the esophagus and regional nodes. Survival was equivalent whether they were treated with radiation alone (n = 18), preoperative radiation and esophagectomy (n = 19), postoperative radiation (n = 5), or a combination of chemotherapy and radiation with or without esophagectomy (n = 20). Fifteen patients had significantly poorer survival after palliative irradiation for overt metastatic disease or severe debility. The pathologic specimens from four of the nine patients who underwent resection showed no histologic evidence of residual tumor; however, tumor recurred in three in the mediastinum, and only one remains alive and free of disease. Four of the 11 patients who received chemotherapy and radiation therapy without resection remain alive and free of disease after further mediastinal irradiation, suggesting a benefit from additional regional therapy. Chemotherapy improved median survival duration and complete response rate but did not produce a significant improvement in survival, as reported in other recent series. PMID- 3112864 TI - Malignant melanoma: analysis of dose fractionation in radiation therapy. AB - Thirty-five patients with 67 measureable cutaneous or lymph node metastases from malignant melanoma were treated with radiation therapy in a variety of total doses and dose fractions. There was no correlation between total dose and response rate. However, there was a strong correlation between fraction size and response rate. There were four (9%) complete responses in 43 lesions treated with fractions less than or equal to 500 rad (5 Gy) compared with 12 (50%) complete responses in 24 lesions treated with fractions greater than 500 rad (5 Gy) (P = .0006). Initial response rate was found to correlate strongly with local control at 1 year. The results were then analyzed with respect to lesion size, cutaneous versus nodal lesions, and site of cutaneous lesion (trunk, head and neck, or extremity). Correlation between fraction size and response rate was independent of lesion size, although there were fewer complete responses with increasing lesion size. Correlation was not seen in nodal lesions but was particularly striking in cutaneous lesions. This correlation was statistically significant only for cutaneous lesions of the extremities. PMID- 3112865 TI - "Ossifying" hemangiomas of the temporal bone: evaluation with CT. AB - Hemangiomas of the temporal bone that affect the facial nerve are more frequent than previously suspected. Six patients with slowly progressive or recurrent facial paralysis were evaluated with computed tomography. In each case, a lesion was demonstrated that enlarged the facial nerve canal and contained intratumoral spicules of bone. Typically the temporal bone was expanded by a lesion with an indistinct margin. Demonstration of the typical radiologic findings, especially the intratumoral bone spicules, makes hemangioma a much more likely diagnosis than schwannoma. PMID- 3112866 TI - Thrombolytic agents for acute evolving myocardial infarction: comparative effects. PMID- 3112867 TI - [Cancer research with Drosophila]. PMID- 3112868 TI - Preceptor programmes: one answer to the professional development needs of nurses. Part two. PMID- 3112869 TI - [The quality of urography with iopamidol and various diuretic agents]. AB - The results obtained in four successive trials based on the analysis of urography performed on patients with normal kidney function are reported. The scores obtained with a non-ionic contrast (iopamidol) were compared with those produced after injecting the same contrast medium with the addition of various diuretics (furosemide, various quantities of 5% glucose solution, 20% mannitol). The results obtained by injecting the diuretic together with the iopamidol were usually unsatisfactory. Injection of diuretic 15 ms after the iopamidol gave better results in the lower urinary tract, particularly the bladder. The best results were obtained by injecting 250 ml, 20% mannitol, after 15 ms. However this technique is not applicable to patients requiring a voiding cystourethrogram due to the inadequate opacification of the urethra it provides. PMID- 3112870 TI - Health risks of PCB spills from electrical equipment. AB - The Southern California Edison Company (SCE) has instituted a series of control strategies designed to minimize human exposure to polychlorinated biphenyls (PCBs) in electrical equipment used on its system. This paper describes a method of analyzing PCB risks using conservative estimates of human intake of PCBs originating from accidental spills from electrical equipment. The PCB releases from the Edison system were determined. The fate of these releases in soil, air, and water was analyzed to determine how much material reaches human receptors. The air and water pathways were determined to be the most likely candidates for the exposure and risk considerations. PCB intake via ingestion of soil at the spill site was neglected as an exposure pathway. Equipment spills without controls resulted in at the most 2 ng/day human intake of PCBs via the water exposure pathway. This was determined to be negligible in comparison with intake rates used in conjunction with the setting of food tolerance levels based on fish being the main dietary pathway of human exposure. The inhalation exposure of the hundred or so persons in the immediate vicinity of a spill was determined to equal the PCB intakes of the fish-eating subpopulation analyzed by the Food and Drug Administration for 2 ppm tolerance standard in the case of no controls or cleanup. Current cleanup procedures assure that even the persons in the immediate area are well below the intake of the subjects in the fish contamination analysis. All exposures were well below a "virtual safe dose" level estimated in the fish tolerance study. PMID- 3112871 TI - Perceived acceptability of risk analysis as a decision-making approach. AB - Three methods for making a consumer product safety decision were evaluated on scales relating to their perceived acceptability, logical soundness, completeness, and sensitivity to moral and ethical concerns. Two of the methods were formalized techniques: cost-benefit analysis and risk analysis. The third method involved abiding by standard industry practices. Other factors in the decision-making context were also varied. The results indicated that formalized techniques were preferred over the standard practices method. Within the formalized methods, cost-benefit analysis was judged less acceptable than a comparable method that did not involve making explicit value tradeoffs. All methods were judged more acceptable when they led to improved product safety. Knowledge of consequences did not exert direct effect on judgments, though it did interact significantly with other variables. The results are discussed in terms of judgmental processes that people apply when evaluating decision methods. PMID- 3112872 TI - Decision analysis and risk management decision making: issues and methods. AB - This paper provides an overview of decision analysis and its use in risk management decision making. The paper discusses the distinctive characteristics of decision analysis and compares these characteristics with those of its principal alternative--cost-benefit analysis. The paper also discusses each of the steps in a decision analysis and the strengths and limitations of the method. PMID- 3112873 TI - [Gonadal dysgenesis associated with gonadotropin and growth hormone deficiencies]. PMID- 3112874 TI - Inhibition of sugar transport across rat jejunum, in vivo, by cupric ions. AB - Cupric ions inhibit galactose absorption by in vivo perfused rat jejunum. It takes some delay for the inhibitory action to display its maximal levels, and previous exposure of the mucosa to Cu markedly increases inhibition. Copper effects were only scarcely reversed by saline solution washing, more effectively by EDTA and more so by dithioerythritol, in no case reaching control values. Absorption of L-sorbose, or that of galactose in the presence of 0.5 mM phlorizin, are not modified by 0.5 mM cupric ions. Cu action may be understood as a selective impairment of the phlorizin-sensitive sugar transport system by binding of the metal to prevailing thiol chemical groups of proteins at the brush border, located at different depth within the thickness of the membrane. PMID- 3112875 TI - [Effect of beta-ecdysterone in competitive cultures of Drosophila melanogaster]. AB - High levels of beta-ecdysterone (more than 1 microgram/ml) have been shown to decrease larva-adult viability and to speed up developmental times when supplied to the media in crowding cultures. The highest doses (100 micrograms/ml) of ecdysterone suppresses almost completely the phenomenon of larval stop in the third instar of development, first reported by our laboratory in overcrowded situations. Thus, one may deduce that stopped larvae could have low levels of ecdysone, and perhaps these are the ultimate physiological cause of their arrested development before the critical larva-pupa molt. PMID- 3112876 TI - Infection of African buffalo (Syncerus caffer) and cattle with Theileria parva lawrencei after serial passage in cattle. AB - The infectivity of a Theileria parva lawrencei stabilate, from a stock derived from an African buffalo (Syncerus caffer) in the Serengeti National Park, Tanzania, was investigated. In the first experiment a buffalo and three cattle were inoculated with a stabilate from a stock passaged three times in cattle. All cattle developed fatal theilerial infections. Isolations from the buffalo by tick feeding and cell culture isolation showed that it was infected with T p lawrencei at the time of inoculation, but the second isolation made 19 days after inoculation behaved like T p parva in cattle, developing a high parasitosis, while the third isolation made three months later behaved like T p lawrencei with low parasitosis. It was concluded that two biological types of T parva could exist in a buffalo at one time, but it was not shown that the buffalo had become a carrier of T p lawrencei adapted to cattle. In the second experiment two buffaloes and three cattle were inoculated with T p lawrencei (Serengeti) stabilate which had been passaged six times through cattle and ticks. The two buffaloes had mild theilerial infections and developed serological titres in the indirect fluorescent antibody test, but the cattle had fatal infections. Tick and cell culture isolations of T parva were possible during the clinical reactions of the buffaloes, but no carrier state was demonstrated. Theileria-infected cell lines were established from the buffaloes and the cattle and were examined using monoclonal antibodies against T parva schizonts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3112877 TI - Effect of infectious stunting syndrome on the immunocompetence of broilers. AB - Immune responses and liveweights of broilers affected with the stunting syndrome (group C) were compared with those of unaffected birds from the same premises (group B) and normal control broilers of the same genetic origin (group A). Measurements of cell-mediated immunity were made using the phytohaemagglutinin (PHA) intradermal test and those of humoral immunity by antibody response to sheep red blood cells. Weekly observations were made of birds aged from two to eight weeks. Throughout the investigation the weekly mean weight of affected birds was very significantly lighter (P less than 0.001) than that of unaffected and control birds. From the second to the sixth week, wing web PHA reactions in group C were very significantly less than those in groups B or A (P less than 0.001), and during the seventh and eighth week wattle PHA reactions were significantly less in group C than those in group B (P less than 0.02). No significant differences were detected between the three groups in humoral immunity; the complete, IgG and IgM, antibody levels being closely similar. The significance and possible practical applications of these findings are discussed. PMID- 3112879 TI - Giant chromosomes in ciliates. PMID- 3112878 TI - Comparative study of ampicillin and amoxycillin after intravenous, intramuscular and oral administration in homing pigeons (Columba livia). AB - Pharmacokinetics of ampicillin and amoxycillin after intravenous, intramuscular and oral administration was investigated in homing pigeons. The pharmacokinetic parameters in a cross-over study after intravenous administration of the sodium salts were comparable. The only significant difference was found for the distribution phase. The bioavailability after intramuscular injection of the sodium salts was especially low for ampicillin (26 per cent, as against 57 per cent for amoxycillin). The mean peak blood levels at 0.5 hours were 13.65 and 28.80 mg litre-1 for ampicillin and amoxycillin, respectively. After oral administration of trihydrate solutions (8 mg ml-1) the bioavailability was 20 and 35 per cent, respectively, and the mean peak blood levels were 8.46 and 16.98 mg litre-1, found at 1.04 and 1.26 hours. The recovery from the droppings, which include in birds the urine fraction as well, was unexpectedly low. Based on controls for recovery of added penicillin from the droppings and uric acid suspensions, indications were found that the pigeon enzymically inactivates penicillins. The in vitro activity of ampicillin against 266 strains of bacteria isolated from birds was determined. The minimum inhibitory concentration (MIC) for 65.4 per cent of the Escherichia coli was lower than 4 mg litre-1, for 91.1 per cent of the Salmonella species was lower than 2 mg litre-1 and for 100 per cent of the Yersinia pseudotuberculosis was lower than 0.25 mg litre-1. Based on these data and a literature study dosage regimens were calculated for MIC values of 0.5 and 2.5 mg litre-1. PMID- 3112880 TI - The white locus of Drosophila melanogaster. PMID- 3112881 TI - The genetic and molecular organization of the dense cluster of functionally related, vital genes in the DOPA decarboxylase region of the Drosophila melanogaster genome. PMID- 3112882 TI - [The effect of bronchodilator on ventilatory response during CO2 rebreathing in patients with asthma]. PMID- 3112883 TI - [Interaction of upper airway reflexes and the chemical respiratory control system]. PMID- 3112884 TI - [Acute effects of ibopamine hydrochloride on hemodynamics, plasma catecholamine levels, renin activity, aldosterone, metabolism and blood gas in patients with severe congestive heart failure]. PMID- 3112885 TI - Effects of hypercapnia on phrenic and stretch receptor responses to lung inflation. AB - To determine if hypercapnia and reflex bronchoconstriction attenuate lung inflation effects on ventilatory activity by indirect effects on intrapulmonary stretch receptors (PSR), phrenic nerve activity and single unit PSR were monitored at controlled levels of static airway pressure (Paw) and arterial PCO2 in 15 anesthetized dogs. Paw in a vascularly isolated lung was varied between 2 and 14 cm H2O at levels of PaCO2 between 35 and 85 mm Hg. PSR activity (n = 38) in fine strands dissected from an otherwise intact vagus nerve and the integrated phrenic neurogram were recorded. The response to Paw varied from one PSR to another, but was consistent in a given unit; PaCO2 had no consistent effect on individual responses. Selected PSR (n = 15) were averaged to yield a population response to Paw; the selection criteria were: phrenic activity responded briskly to Paw and measurements were made at three levels of PaCO2. Average PSR discharge increased linearly with Paw but was unaffected by PaCO2. On the other hand, phrenic burst frequency decreased as Paw increased and hypercapnia attenuated the slope of this relationship. These results suggest that effects on the relationship between PSR activity and Paw cannot account for attenuation of the relationship between phrenic frequency and Paw in hypercapnia. The effect of PaCO2 on the phrenic frequency vs Paw relationship probably arises from integrative mechanisms in the central nervous system. PMID- 3112886 TI - [Nasal sinus polyposis: use with an eye toward therapy of a in vitro test to measure the lipoxygenase pathway]. PMID- 3112887 TI - [Result of the treatment of juvenile papillomatosis of the larynx. Apropos of 158 cases]. PMID- 3112888 TI - The human gonadotropic adenoma: pathologic diagnosis and hormonal correlations in 26 tumors. AB - Twenty-six out of 400 surgically removed pituitary tumors were identified as gonadotropic adenomas (frequency 6.25%). Morphologic, immunocytochemical, and hormonal characteristics of the gonadotropic adenoma are described. The following morphologic characteristics may suggest the diagnosis: arrangement in cords of cells showing signs of cellular activity, secretory granules, which vary in electron density, form, and size (mean diameter 150 nm) and which are numerous in the extensions near the capillaries, and a rough endoplasmic reticulum arranged in short cisternae. However, owing to the morphofunctional variations from one adenoma to another, we consider that only immunoreactivity with gonadotropin antisera proves the diagnosis. Because the material used to generate the gonadotropin antisera was purified but not pure, for precise characterization of the immunoreactivity, absorption tests with various antigens have to be performed. FSH-LH adenomas (n = 14), FSH adenomas (n = 7), and alpha-subunit adenomas (n = 5) but no LH adenomas were identified in our series. No evident morphologic difference related to the type of immunoreactivity and to the sex was found. Almost all the tumors were large with visual signs caused by suprasellar extension. A recurrence following adenomectomy was noted with a frequency of 12%. The diagnosis of gonadotropic adenoma was considered preoperatively in six out of 26 patients only, on the basis of increased serum gonadotropin levels. Correlations between hormonal levels and pathologic data were established in 17 patients. Seven tumors were associated with high serum gonadotropin levels (FSH and LH: three patients and FSH alone: four patients). In ten cases, the serum gonadotropin levels were normal but serum alpha-subunit assay had not been performed. For the pathologist systematically testing the adenomas with many antisera, gonadotropic adenomas are not as rare as for the clinician. Immunocytochemical studies with gonadotropin antisera and serum gonadotropic determination must be performed in all tumors, especially in those pituitary adenomas that appear nonfunctional. PMID- 3112889 TI - Radiation therapy for lung cancer: nursing considerations. PMID- 3112890 TI - [Diaphragmatic eventration (unilateral elevation) and megacolon]. PMID- 3112891 TI - [A pregnant woman with active ulcerative colitis maintained on total parenteral nutrition]. AB - A 28-year-old woman was admitted to our hospital with complaints of mucosanguinous stool and low grade fever. She was diagnosed as a typical chronic continuous type of ulcerative colitis by the findings of barium enema and colonoscopy. Since she had an allergy to sulfasalazine, prednisolone was chosen. She became pregnant during an active stage while being treated with 20 mg of prednisolone a day. Prednisolone was withdrawn to avoid the side-effects of the medicine on the fetal outcome. This resulted in her symptoms becoming far worse and the oral ingestion being discontinued. Total parenteral nutrition (TPN) was required under careful nutritional management. The TPN consisted of glucose, electrolytes, amino acids, vitamins, trace elements and intravenous lipid preparation. Her total energy intake was 2320 kcal a day. Vitamins were administered to her on the bases of the guideline of the American medical association. Rapid turnover proteins, transferrin, vitamins, trace elements and amino acids in addition to routine laboratory tests were measured to estimate her nutritional condition. The data showed that biotin was 10 times lower than the expected value and that other factors were within normal limits. This is the first case in Japan where a woman suffering from an active ulcerative colitis was treated with TPN and delivered of a healthy baby. We concluded that TPN under careful control was useful in the nutritional management and therapy of the pregnant patient who suffered from severe colitis. We believe that the amount of biotin's supplementation should be increased in this type of case because it was 10 times lower than the normal value, although the deficiency symptoms did not develop. PMID- 3112892 TI - [An autopsy case of lymphoid interstitial pneumonia with monoclonal gammopathy]. AB - An autopsy case of a 75-year-old female with lymphoid interstitial pneumonia with monoclonal gammopathy of IgA kappa type is reported. The patient was admitted to UOEH Hospital suffering from a cough, sputum and fever. After examining a specimen of transbronchial lung biopsy and chest X ray films, lymphoid interstitial pneumonia was suspected. Serum immunological examination showed monoclonal IgA kappa type hypergammaglobulinemia. Marked clinical and radiological improvement was attained after prednisolone administration. After 16 months, however, the patient deteriorated and expired on January 21, 1986. On postmortem examination, a number of plasma cells as well as lymphoid cells were seen to have infiltrated in the thickened interalveolar septa and the parenchyme of the lymph nodes throughout the whole body. The architecture of lymph nodes remained preserved, while the cortex as well as the medulla was almost completely replaced by plasma cells and lymphoplasmacytoid cells. Immunohistochemical examination demonstrated the presence of IgA kappa in the plasma cells and some of the lymphoplasmacytoid cells in both lymph nodes and lungs. These findings suggest that the proliferating plasma cells and lymphoplasmacytoid cells were in neoplastic or preneoplastic states and support the hypothesis that lymphoid interstitial pneumonia may be an expression of the systemic lymphoproliferative disorders in the lung. PMID- 3112893 TI - Prevention, treatment and healing of pressure sores in long-term care patients. PMID- 3112894 TI - [Aerosol therapy]. PMID- 3112895 TI - [New perspectives in the immunologic exploration of rheumatic diseases]. PMID- 3112896 TI - [Do monoamine oxidase B inhibitors represent hope for Parkinson's disease patients?]. PMID- 3112897 TI - [Practical use of ambulatory long-term EEG recording]. PMID- 3112898 TI - [Venous complications of peripheral parenteral nutrition]. PMID- 3112900 TI - [Congenital coagulation disorders in children. I. Hemophilia A]. PMID- 3112899 TI - [Diagnosis in pediatrics]. PMID- 3112901 TI - [Autoimmune hemolytic anemia in children]. PMID- 3112902 TI - [Viral myocarditis with immunologic mechanisms in children]. PMID- 3112903 TI - [Aspects of lymphostasis implicated in the pathogenesis of primary lymphedema in children]. PMID- 3112904 TI - [Seckel-Wirchow syndrome (bird-headed nanism)]. PMID- 3112905 TI - [Implication of coagulation in infants with severe acute diarrhea disease]. PMID- 3112906 TI - [Congenital coagulation disorders in children (II) (Willebrand's disease, Christmas disease, factor IX, XI, XII, I, II, VII and V deficiencies)]. PMID- 3112907 TI - [Extraarticular manifestations in chronic juvenile arthritis]. PMID- 3112908 TI - [Borderline hypertension in the adolescent--a fact. Epidemiologic and physiopathologic significance]. PMID- 3112909 TI - [The common arterial trunk. Presentation of a case with particular morpho pathological aspects]. PMID- 3112911 TI - The preparation of visually guided saccades. PMID- 3112910 TI - [Abdominal masses in children: problems of diagnosis]. PMID- 3112912 TI - DC potentials of the cerebral cortex. Seizure activity and changes in gas pressures. PMID- 3112913 TI - [Post-aggression denutrition. Indications for parenteral feeding]. PMID- 3112914 TI - [Energy and nitrogen requirements--vitamins, electrolytes and trace elements requirements]. PMID- 3112915 TI - [Clinical, biological and immunological surveillance of parenteral feeding. An evaluation]. PMID- 3112916 TI - [Prolonged parenteral feeding at home]. PMID- 3112917 TI - [Methods of parenteral nutrition]. PMID- 3112918 TI - [Infectious complications of parenteral feeding--various infections and catheters: something to reflect on]. PMID- 3112919 TI - Some chemical properties of tissue plasminogen activator purified from paranasal mucous membrane. AB - Plasminogen activator (PA) was purified from an acetone powder preparation of paranasal mucous membrane with chronic sinusitis, and some chemical properties of the purified PA were investigated in this paper. Zn-imminodiacetate affinity chromatography, lysine sepharose affinity chromatography and ultrafiltration for concentrating a PA fraction were consecutively performed to purify the PA from the acetone powder preparation. Finally, gel filtration was performed using Sephacryl S-200 in order to estimate the molecular weight of the purified PA. The purified PA in this experiment showed a stronger affinity to fibrin than urokinase did. The molecular weight of the purified PA was estimated to be 65,000 to 70,000 daltons as determined by Sephacryl S-200 gel filtration. The Km of the purified PA was 0.11 mM. From these results, it is apparent that the PA purified from an acetone powder preparation of paranasal mucous membrane belongs to the class of tissue type plasminogen activators (t-PA). PMID- 3112921 TI - Twenty-one-month evaluation of misoprostol for carcinogenicity in CD-1 mice. AB - Misoprostol, a synthetic prostaglandin E1 methyl ester analogue with anti-ulcer potential, was evaluated for its carcinogenic potential in CD-1 strain mice. The compound was given daily by gavage at 160, 1,600, and 16,000 micrograms/kg for 21 months. Necropsies were done on all animals and the incidences of non-neoplastic and neoplastic changes analyzed for significance by life table methods. The only statistically significant non-neoplastic compound-related findings were epithelial hyperplasia and hyperkeratosis of the gastric mucosa and hyperostosis of bone in the marrow cavity of sternebrae and femurs. The changes in the gastric epithelium are characteristic of some prostaglandins and were expected. The bone hyperostosis was associated with misoprostol in high dosages, and was considered unique to the mouse. Other non-neoplastic findings were typical of known spontaneous conditions in mice. The most frequent neoplasm was the hepatocellular adenoma followed by lymphosarcoma, lung alveolar carcinoma, and Harderian gland adenoma. Several proliferative lesions of the duodenum were considered to be spontaneous. These were focal avillous hyperplasia, focal atypical hyperplasia, and junctional polyp. There was no evidence that misoprostol is carcinogenic for CD-1 mice. PMID- 3112920 TI - Two-year evaluation of misoprostol for carcinogenicity in CD Sprague-Dawley rats. AB - The carcinogenic potential of misoprostol, a synthetic prostaglandin E1 analogue with anti-ulcer potential, was evaluated in CD Sprague-Dawley rats. The compound was given daily by gavage at 24, 240, and 2,400 micrograms/kg, up to 150 times the daily human dose for 2 years. Necropsies were done on all animals and the incidences of non-neoplastic and neoplastic changes analyzed for significance by life table methods. The only statistically significant non-neoplastic finding was epithelial hyperplasia and hyperkeratosis of the gastric mucosa. These changes, which are characteristic of some prostaglandins, were expected. Other non neoplastic findings were typical of known spontaneous conditions in this strain of rats. The most frequent neoplasm was the pituitary adenoma, followed by the mammary fibroadenoma, mammary adenoma, mammary adenocarcinoma, and thyroid C-cell adenoma. A rare neoplasm, squamous cell carcinoma of the ovary was found in two rats. There was no evidence that misoprostol is carcinogenic for CD Sprague Dawley rats. PMID- 3112922 TI - Induction of the placental form of glutathione S-transferase by lead nitrate administration in rat liver. AB - The administration of a single dose of lead nitrate to male Wistar rats caused an increase of a polypeptide in the liver cytosol that cross reacted with the anti rat antibody of the placental form of glutathione S-transferase (GST-P). GST-P appeared when doses of lead that induced liver cell proliferation were given (5 and 10 micromoles/100 g of body weight). Recently, it has been shown that rat hepatic nodules also exhibited an increased content of the placental form of GST P. The induction of GST-P by lead together with other biochemical effects exerted in the liver by this metal, suggests that some chemicals may induce in rat liver a biochemical pattern similar, in some aspects, to that exhibited by carcinogen induced hepatocyte nodules. PMID- 3112923 TI - Three stage carcinogenesis in mouse skin--recent results and present status of an advanced model system of chemical carcinogenesis. AB - In the three stage model of carcinogenesis in mouse skin, to a certain compartment of normal cells new and adverse biological properties are imposed by the initiator DMBA yielding 'potential tumor cells,' or 'initiated cells.' These initiated cells exhibit a selective advantage of growth over surrounding normal cells if exposed to DTE promoters. The new properties may result from a genomic mutation associated with an increase of density, affinity or cooperativity of certain membrane receptors as compared to normal cells. Complete promoters, such as TPA, but not incomplete promoters such as RPA may impose a second additional genomic or epigenomic insult onto initiated cells ('conversion'). As a consequence, initiated cells become ready to respond to unspecific mitogenic stimuli ('propagation'), as provided by hyperplasiogenic agents. The initiation/promotion model of mouse skin presents new and attractive possibilities to apply the oncogene approach for further in-depth analysis of the molecular mechanisms of its stages. It remains to be seen to what extent molecular events demonstrated causative for the stages in the mouse skin model are applicable also to stages in multistage models of chemical carcinogenesis operational in other target tissues. PMID- 3112924 TI - [Metals and polychlorinated compounds in eels from the Gdansk bay and adjacent waters. II. Eels from the Firth of Vistula]. PMID- 3112925 TI - Plasma fibronectin and factor XIII in nephrotic syndrome. AB - When compared to control subjects plasma fibronectin and factor XIII as well as plasma fibrinogen, factor VIII-related antigen and serum cholinesterase were found to be significantly increased in nephrotic patients. Factor XIII activity was positively correlated with serum cholinesterase, while plasma fibronectin displayed weak correlations with plasma fibrinogen and factor VIII-related antigen. It is considered that increased levels of factor XIII and fibronectin should be related to the intensity of the liver's compensative response to proteinuria, although their turnover rates and the signals triggering this response may differ. It is however difficult to assess possible consequences of the above-mentioned changes for the evolution of the nephrotic syndrome. PMID- 3112926 TI - [Permanent constriction of the jaws due to progressive ossifying myositis]. AB - A case is reported of progressive ossifying myositis (fibrodysplasia ossificans progressiva, Munchmeyer's disease) with onset at 16 years of age by a lesion of internal pterygoid with limitation of opening of mouth. Surgery to relieve ankylosis was followed by recurrence. Diagnosis was established only after the appearance of lesions in other regions (sternocleidomastoid, latissimus dorsi, lumbar muscles...). Clinical and paraclinical signs of this exceptionally rare disease are reviewed and diagnostic difficulties at onset of the disease discussed. Treatment of acute myositis episodes with diphosphonates delays passage to the ossification stage, allowing local surgery to be performed with less risk of relapse. PMID- 3112927 TI - [The effect of age on the 24-hour retention of TC-99m methylene diphosphonate in rats]. PMID- 3112928 TI - Prostaglandin synthesis in the human gastrointestinal mucosa. AB - Prostaglandins derive from polyunsaturated fatty acids, of which arachidonic acid is the most abundant. Arachidonic acid occurs in all cell membranes, where it is bound to phospholipids and can, once liberated by phospholipases, be metabolized by cyclooxygenase into prostaglandins and thromboxanes and by lipoxygenases into hydroxyacids, leukotrienes and lipoxins. In most studies on prostaglandin formation in the human gastrointestinal mucosa PGE2 and PGF2 alpha seem to be the regularly occurring products. Quantification of mucosal prostaglandin synthesis in vivo is problematic. Mechanical handling of tissues immediately activates arachidonic acid metabolism, and the determination of "tissue levels" of prostaglandins or prostaglandin biosynthesis in biopsy specimens ex vivo thus becomes unreliable as a measure of in vivo formation. A more reliable approach may be to measure prostaglandins in gastrointestinal luminal contents, which can be obtained atraumatically. Most measurements are made by radioimmunological methods, but the specificity of most assays has not been satisfactorily examined. More specific methods such as gas chromatography-mass spectrometry should be used to validate of a radioimmunoassays. Prostaglandin E2, which can be measured by gas chromatography-mass spectrometry, is regularly found in human gastroduodenal luminal contents. Exposure of the mucosa to hydrochloric acid increases the output of PGE2 to the lumen, indicating increased mucosal PGE2 formation during physiological activation of mucosal defense mechanisms. PMID- 3112929 TI - A B cell growth factor-dependent cell line derived from a human lymphocytic nodular lymphoma. AB - A B cell line derived from a human nodular lymphocytic lymphoma (Brill-Symmers) was shown to be dependent on the presence of a low molecular weight B cell growth factor (BCGF) for its growth in vitro. The caryotype was normal and no contamination with Epstein-Barr virus (EBV) could be detected. These cells did not respond to recombinant gamma interferon or to recombinant human interleukin 2 (IL-2), although they displayed a weak density of IL-2 receptor sites. They were both responsive to and dependent on BCGF for their multiplication in vitro. Furthermore, the putative receptor for this growth factor (CD23) was detected on these cells and the BCGF-dependent proliferation could be blocked by a monoclonal anti-CD23 antibody. A tumour-derived cell line like this provides an interesting model for studying the mechanisms regulating B cell growth and the early events leading to the process of B cell immortalization. PMID- 3112930 TI - Enzymatic fragmentation of an unusual human IgG2 (Kva) myeloma protein. AB - The Kva IgG2(k) myeloma protein showed a complete resistance to papain in the presence of cysteine at neutral pH, and a higher resistance to trypsin and alpha chymotrypsin digestion than other IgG2 proteins. On the other hand, the Kva molecule was cleaved by pepsin at low pH to give the expected F(ab')2 fragment. When the cleavage conditions were altered, it was possible to obtain Fab, Fc, and Fc' fragments from this molecule as well. The Fab/c fragment and FacbFc' complex were also obtained, which have not previously been reported from human IgG2 molecules. Incubation at elevated temperatures (45-50 degrees C) and/or lower pH resulted mainly in enzymatic attack on the C terminal side of the hinge. It was necessary to destroy the hinge by reduction or to expose the Kva molecule at 70 degrees C or at lower pH (2.5) prior to digestion to facilitate enzyme digestion on the NH2 terminal side of the hinge. These results indicate that the hinge region of the Kva molecule has an unusually compact structure, which makes it extremely resistant to proteolysis. PMID- 3112931 TI - Kinetics of Ca2+ uptake into lectin-induced secondary lymphocytes during reactivation with concanavalin A or interleukin 2. AB - The kinetics of Ca2+ uptake into lectin-induced secondary lymphocytes was studied during reactivation to DNA synthesis with concanavalin A (Con A) or interleukin 2 (IL-2). IL-2 did not cause any significant uptake of Ca2+ into the lymphocytes, while Con A induced an accumulation of Ca2+ into the lymphocytes which reached a maximum 1 to 2 h after the addition of the lectin. The time during which Ca2+ uptake occurred corresponded to the time of dependence on extracellular Ca2+ for lectin-induced DNA synthesis. The increased rate of Ca2+ accumulation and the shortened Ca2+ dependence period of secondary lymphocytes as compared with primary lymphocytes could explain the ability of secondary lymphocytes to display an accelerated response, in terms of DNA synthesis, to re-stimulus. PMID- 3112932 TI - Induction of responsiveness to interleukin 2 in mouse lymphocytes by synergistic action of ionophore A 23187 and diacylglycerol. AB - We investigated whether the protein kinase C-binding agents 12-O-tetradecanoyl phorbol-13-acetate (TPA) and 1-oleoyl-2-acetyl-rac-glycerol (OAG) induced reactivity to interleukin 2 (IL-2) in mouse lymphocytes. 10(-8) M TPA was a strong inducer of reactivity to IL-2 measured by [3H]thymidine incorporation. In contrast OAG alone (6-25 micrograms/ml) did not induce a significant IL-2 mediated proliferative response. Cells stimulated with the ionophore A 23187 + OAG neither proliferated nor produced IL-2. In contrast, cells stimulated with A 23187 + OAG + IL-2 showed a significant proliferative response, indicating the expression of functional high affinity IL-2 receptors. The expression of reactivity to IL-2 induced by A 23187 + OAG was inhibited by 0.04 mM Mn2+; in contrast the TPA-mediated induction of IL-2 responsiveness was not affected by Mn2+. The data suggest differences in the mechanism of induction of IL-2 responsiveness by the two protein kinase C-binding agents, TPA and OAG. PMID- 3112933 TI - Selective modulation of the CD4 molecular complex by Pseudomonas aeruginosa alkaline protease and elastase. AB - The binding of monoclonal antibodies against CD4 was specifically inhibited by treatment of human CD4+ cells with either alkaline protease (AP) or elastase (Ela), purified from Pseudomonas aeruginosa. Binding of antibodies against CD3 (pan T), CD5 (pan T), CD8 (T suppressor/cytotoxic), HLA-ABC, HLA-DR, HLA-DQ, HLA DP/DR, and beta 2 microglobulin was not inhibited by AP or Ela. Heat-inactivation of the proteases at 65 degrees C for 20 min or treatment with the metal chelator EDTA abolished the inhibitory activity of both proteases. These findings may serve to develop novel immunological methods for the isolation and study of the lymphocyte CD4 structure, which plays an important part in the immune response. PMID- 3112934 TI - Penicillin concentration in saliva and its influence on bacterial interference. AB - The aim of the investigation was to study the influence of various penicillin levels on the interference between alfa- and beta-streptococci based on antibiotic levels registered after oral intake of penicillin tablets. It was found that penicillin was released from ordinary sugar coated tablets already in the mouth resulting in concentrations in saliva above the MIC of most penicillin sensitive microorganisms during the first 2 min. This was followed by a decrease of the alfa-streptococcal flora. It was also shown that penicillin levels above the MIC of alfa-streptococci resulted in prolonged survival of beta-streptococci as compared to that noted at penicillin levels above the MIC of beta-streptococci but below that of the alfa-strains. At this latter level a synergistic effect between penicillin and interfering alfa-streptococcal strains could be demonstrated. PMID- 3112935 TI - The regression line for erythromycin is not valid for beta-hemolytic streptococci group A. AB - The antibacterial activity of erythromycin to 50 beta-hemolytic streptococci group A was assessed using disc diffusion and MIC techniques on solid media at pHs 6, 7 and 8 in CO2, aerobic and anaerobic atmospheres. The majority of the strains were only intermediately sensitive to erythromycin according to the disc diffusion method, whereas they were sensitive as judged by the MIC determination. This demonstrates that the regression line is invalid for the drug-bug combination of erythromycin and beta-hemolytic streptococci group A. It was also shown that the activity of erythromycin is reduced at a lower pH and in CO2 incubation. PMID- 3112936 TI - The scanning electron microscopy/replica technique and recent applications to the study of fossil bone. AB - The SEM/replica technique employs high resolution replica materials in order to reflect microstructural details of specimens, such as fossil bones, which cannot be observed directly. The described technique is simple, provides excellent resolution, is maximally adaptable to field and laboratory settings, and is applicable to large and topographically complex bone surfaces. The advent of the technique has made it largely possible to address certain issues in anthropology and paleontology. These contributions have principally been concerned with taphonomy as the study of the bone damage process, and bone biology as it relates to bone growth remodeling processes characterizing the facial growth of our early fossil hominid ancestors. PMID- 3112938 TI - Replication technique for studying microstructure in fossil enamel. AB - The present paper describes a two stage impression technique using a silicone elastomer suitable for field replication studies; which requires high dimensional stability, defined resolution, and being capable of reproducing inaccessible details. A test object consisting of etched pearlite possessed fine detail [greater than 1 micron to less than 0.1 micron] which was suitable for testing negative/positive replica combinations. Coltene President light-body impression material was capable of resolving parallel side depressions of widths greater than or equal to 0.2 micron, and it possesses very good dimensional stability with time, allowing the production of positive casts to be deferred for several months. Low viscosity Spurr resin reproduced this detail, and flowed into inaccessible sites. Although there was evidence of bulk contraction on curing, there was no significant shrinkage on flat [linear] surfaces or in vertical relief dimensions. Replicas of fractured hominid teeth showed good surface detail, and reproduction of inaccessible three-dimensional features on enamel surfaces. Enamel prism shape was pattern 3. PMID- 3112939 TI - [Prognostic factors in bacterial meningitis in adults. Retrospective analysis of 46 patients]. AB - Clinical and laboratory data on 46 patients with acute bacterial meningitis were analyzed in a retrospective survey. The incidence of bacterial meningitis in hospital admissions was 1.3% and the mortality 33%. Streptococcus pneumoniae was the most frequent etiologic agent. Mortality was highest for pneumococcal meningitis and was higher in patients over 50 years of age (83% vs 25%, p less than 0.05). The initial stage of consciousness was prognostically important. All awake patients survived, while the more impaired the consciousness (from lethargy to coma), the higher the mortality (19%, 25%, and 78% respectively). Seizures and paresis of the third cranial nerve were significantly higher in lethal cases. Brain edema was the leading cause of death (60%). The interval between hospital admission and start of antibiotic treatment was crucial for prognosis. Patients who received the first dose of antibiotics within 3 hours after admission had a mortality of 13%, while a delay of 6-24 hours increased the mortality to 3/3. PMID- 3112937 TI - Quantitative analysis of occlusal microwear in Australopithecus and Paranthropus. AB - Quantitative analysis of microwear features preserved on the occlusal surfaces of the M2s of southern African specimens of Australopithecus and Paranthropus (the so-called 'gracile' and 'robust' australopithecines) reveals that there is no striking relationship in either taxon between occlusal facet inclination and the incidence of wear features. Within each taxon, Phase I and Phase II facets tend to differ in a similar manner in the total number of wear features, the percentage frequency of pitting, and in the orientation of wear scratches. Nevertheless, Paranthropus molars tend to display significantly greater numbers of microwear features on both Phase I and II facets than do Australopithecus homologues, and Paranthropus molars also evince significantly higher proportions of occlusal pitting on these surfaces. Paranthropus and Australopithecus crowns also differ significantly in the degree by which the occlusal wear scratches vary in their orientation. On each facet, Australopithecus tooth scratches display a greater degree of directional similarity. The differences between the Phase I and Phase II facets of Australopithecus and Paranthropus M2s suggest that the dietary items involved in the production of these observed patterns differed also. The diets of these Plio-Pleistocene hominids appear to have been qualitatively dissimilar. PMID- 3112941 TI - A cost-effective approach to SCI health maintenance. PMID- 3112940 TI - [Imaging of complications of arthroplasty of the hip and knee]. AB - On the basis of the literature and their personal experience, the authors describe the semiology, limits and complementary character of the current imaging techniques in the diagnosis of hip and knee arthroplasty failures. PMID- 3112942 TI - The three-dimensional structure of Asn102 mutant of trypsin: role of Asp102 in serine protease catalysis. AB - The structure of the Asn102 mutant of trypsin was determined in order to distinguish whether the reduced activity of the mutant at neutral pH results from an altered active site conformation or from an inability to stabilize a positive charge on the active site histidine. The active site structure of the Asn102 mutant of trypsin is identical to the native enzyme with respect to the specificity pocket, the oxyanion hole, and the orientation of the nucleophilic serine. The observed decrease in rate results from the loss of nucleophilicity of the active site serine. This decreased nucleophilicity may result from stabilization of a His57 tautomer that is unable to accept the serine hydroxyl proton. PMID- 3112943 TI - Molecular diversity of the human T-gamma constant region genes. AB - The human T cell antigen-receptor gamma chain, which is expressed on the surface of a subpopulation of CD3+ T lymphocytes, exhibits size polymorphism and varies in its ability to form disulfide bonds with a second polypeptide. Analysis of both genomic and complementary DNA clones encoding the human gamma polypeptide shows differences in lengths of the coding portions of the two constant region genes, C gamma 1 and C gamma 2. A single second-exon segment is always present in the C gamma 1 gene. C gamma 2 alleles containing either duplicated or triplicated second-exon segments are present in the normal human population and are expressed as messenger RNAs. Furthermore, a cysteine residue, encoded by the second exon of C gamma 1 and probably involved in interchain disulfide bridging, is absent in all C gamma 2 second-exon segments. These differences between C gamma 1 and the two alleles of C gamma 2 may explain the variability in molecular weight and disulfide bonding of gamma molecules expressed in different cells. PMID- 3112944 TI - Discovering microbes with a taste for PCBs. PMID- 3112945 TI - Medical management of the infant or child with chronic liver disease. PMID- 3112946 TI - Recent developments in perinatal and neonatal medical ethics: a US perspective. PMID- 3112947 TI - [Psychological help. The perspectives of C. Rogers]. PMID- 3112948 TI - [Synthesis of the Instruction on Respect for Nascent Human Life and the Dignity of Procreation. A response to some urgent questions]. PMID- 3112949 TI - [Human reproduction. The challenge of the new technologies]. PMID- 3112950 TI - [Profile of the intensive care unit nurse]. PMID- 3112951 TI - [Nursing care of the patient with acute kidney failure]. PMID- 3112952 TI - [Acquired immunodeficiency syndrome (AIDS): a world challenge]. PMID- 3112953 TI - [Intensive care units in public health]. PMID- 3112954 TI - [History of transfusions. Blood is a product that should be donated by those who can to those who need]. PMID- 3112955 TI - [Work technics. How to organize a scientific paper]. PMID- 3112956 TI - [Eruptive diseases and pregnancy]. PMID- 3112957 TI - [The risk that tobacco represents for the health of the nonsmoker]. PMID- 3112958 TI - The radiology of skeletal elements in the subtibial region: incidence and significance. AB - The os subtibiale is a rare, genuine accessory bone and normal variant related to the posterior colliculus of the medial malleolus. Only one example was found in the radiographs of the ankles of 700 patients examined. It can be differentiated from other ossicles in this region by its relatively large size, its rounded and well-defined shape, and its posterior position. Ossicles related to the anterior colliculus, which forms the tip of the malleolus, are smaller and were present in 15 ankles (2.1%). These may represent unfused secondary ossification centres. Post-traumatic ossification is the probable explanation for the small, angular and less well-defined ossified elements encountered. The overall incidence of ossification in the subtibial region in the 700 ankles studied was 4.6%. PMID- 3112959 TI - Dorsal defect of the patella: concept of its origin and relationship with bipartite and multipartite patella. AB - In a series of 2286 single radiographic examinations of the knee in 1985, 6 dorsal defects of the patella (DDP) were detected. The diagnosis was made if a round lucent lesion of the dorsal superolateral surface of the patella was found abutting against articular cartilage. In four of our patients, an association with a multipartite patella (MP) was found. Biopsy of one lesion showed dense connective tissue and areas of bone necrosis. In one patient, the pattern of reossification of the lesion could be demonstrated. Our observations provide further evidence that the DDP is a stress-induced anomaly of ossification rather than a post-traumatic subarticular cyst of the patella, a diagnosis sometimes suggested by the clinical context. The initial lesion is probably a traction lesion at the insertion of the vastus lateralis muscle rather than ulceration of articular cartilage. We suggest a possible relationship between dysfunction of the quadriceps mechanism, patellar subluxation, and the genesis of the DDP. PMID- 3112960 TI - Evaluating healthy days of life gained from health projects. AB - This paper draws attention to the importance of incorporating weights for time preference and productivity in using the concept of healthy days of life lost to evaluate healthy projects. Two alternative health strategies are defined for Ghana and evaluated, over a range of discount rates from 0 to 20%, with regard to the present value of productive life saved. It is found that the relative ranking of the projects is sensitive to the choice of discount rates. The sensitivity of disease rankings to the underlying morbidity and fatality rates is also examined and the results underline the importance of obtaining better epidemiological baseline data and information on project effectiveness if the potential usefulness of the healthy days of life approach to project evaluation is to be fully realized. PMID- 3112961 TI - Cultural change, growth and feeding of children in an isolated rural region of Yemen. AB - This paper reports a study on the growth and feeding patterns of children from an isolated region of North Yemen. Marasmus was extremely common and was associated with poor infant feeding practices--particularly the widespread use of bottled milk--and frequent infections. Despite the appearance of a homogeneous traditional society, there were significant differences in the growth of children from adjacent areas. Children from a small township serving as the administrative centre of the region grew more poorly and had a higher mortality than those from the immediate rural hinterland. While poorer living conditions and more frequent infections may explain much of the worse growth and higher mortality of the township children, it is likely less adequate patterns of feeding, particularly greater use of artificial milk, also contribute significantly to the observed difference in growth. Despite the remote rural setting of the study, feeding patterns and growth may be influenced by a number of social factors associated with 'urbanisation'. PMID- 3112962 TI - Guillain-Barre syndrome in kappa light chain myeloma. AB - We have reported a case of Guillain-Barre syndrome developing in a patient with kappa light chain myeloma and acute renal failure. No improvement in acute polyneuritis was observed with serial plasma exchange. At autopsy, peripheral nerves showed no evidence of perivascular lymphocytic infiltration or demyelination, no amyloidosis, and no myelomatous infiltration. PMID- 3112964 TI - [Basic trends in the development of public health in Finland]. PMID- 3112963 TI - Vaginal physiology in postmenopausal women: pH value, transvaginal electropotential difference, and estimated blood flow. AB - Basal vaginal physiologic study, including pH values in various locations, transvaginal electropotential difference, and blood flow estimation, was done twice in a group of 34 untreated postmenopausal women. Plasma hormone levels (gonadotropins and estrogens) and vaginal cytology were also obtained to confirm the estrogen deficiency state. The pH values in the vaginal fornices were significantly lower than those in the middle portion of the vagina. Sexually active women had significantly lower pH values than sexually inactive women. The transvaginal electropotential difference and estimated blood flow values were lower than those of premenopausal women reported in the literature, indicating impaired vaginal transport mechanism and decreased vaginal blood flow. The close approximation of the data obtained in the two measurements one month apart attests the reproducibility of the methods used. PMID- 3112965 TI - Traumatic tetraparesis: a rare neurologic complication in ankylosing spondylitis with ossification of posterior longitudinal ligament of the cervical spine. A case report. PMID- 3112966 TI - Comparative in-vitro activity of enoxacin against penicillinase- and non penicillinase-producing Neisseria gonorrhoeae. AB - The in-vitro antigonococcal activity of enoxacin was measured by a broth microdilution method. Comparisons were made with five clinically relevant marketed drugs against 23 clinical isolates of Neisseria gonorrhoeae, including several penicillinase producers as well as multiply resistant strains. Results showed that enoxacin possessed potent activity against all organisms tested, with MIC values ranging from less than or equal to 0.013 to 0.05 micrograms/ml. PMID- 3112967 TI - Infections due to beta-lactamase-producing Neisseria gonorrhoeae at the University Hospital Medical Center, Kuala Lumpur, Malaysia. AB - The incidence of infections due to beta-lactamase-producing Neisseria gonorrhoeae is increasing in many parts of the world. An epidemiologic survey of infections caused by beta-lactamase-producing strains of N. gonorrhoeae at the University Hospital, Kuala Lumpur, from February 1977 to December 1985 (106 months) showed that the incidence rose from 4.8% (two cases) in 1977 to 49.4% (39 cases) by the end of 1985. The highest incidence of gonococcal infections was found to be in the group aged 20-39 years; the male-to-female ratio was 1.55:1. The mean inhibitory concentrations of benzylpenicillin were 0.12 microgram/ml for non-beta lactamase-producing strains and 16 micrograms/ml for isolates of N. gonorrhoeae that produce beta-lactamase. PMID- 3112968 TI - Endometrial damage in acute salpingitis. AB - Histologic and bacteriologic analyses of endometrium were performed before and on day 15 after minocycline treatment of 20 patients with acute salpingitis. Endometritis was diagnosed in 15 patients before and in nine after treatment. Neisseria gonorrhoeae was recovered from the cervix and endometrium of seven patients but was not isolated after treatment. Chlamydia trachomatis was recovered from the cervix of eight, and from the endometrium of three patients, two of whom had negative cervical cultures. After treatment C. trachomatis was recovered from the cervix of three patients, although two of them had taken aluminum hydroxide for gastric symptomatology during minocycline treatment. Culture of an endometrial specimen revealed no growth of C. trachomatis. The histologic study revealed plasma cell infiltrates in specimens from patients who had cultures positive for C. trachomatis. The results showed that although endometritis is an important manifestation of acute salpingitis, there is no correlation between severity of endometritis and degree of tubal damage. PMID- 3112970 TI - [Study of "lupus-type" anticoagulant using diluted Russell's viper venom time. Study of 16 patients]. PMID- 3112969 TI - Suboptimal efficacy of erythromycin and tetracycline against vaginal Ureaplasma urealyticum. AB - Female sexual contacts of men with nongonococcal urethritis (NGU) are often treated with either tetracycline or erythromycin because these antimicrobial agents are active in vitro against most strains of both Chlamydia trachomatis and Ureaplasma urealyticum, the major identified causes of NGU. Both drugs are known to be active against genital C. trachomatis infections in women. In this study, tetracycline and erythromycin base were evaluated for efficacy against U. urealyticum in the vagina. U. urealyticum was isolated from 400 (85%) of 473 women. Among women whose cultures for U. urealyticum were initially positive, cultures were negative at follow-up for one (1%) of 95 receiving no treatment, four (6%) of 71 receiving erythromycin base (250 mg four times daily for seven to ten days), and 59 (42%) of 142 receiving tetracycline (500 mg four times daily for five to ten days). Thus, none of the regimens is reliable for eradication of U. urealyticum from the vagina. PMID- 3112971 TI - Changing needs of patients and families in long-term care facilities: implications for social work practice. AB - The purpose of this paper is to describe the changing needs of patients in long term care facilities and their families. The argument will be made that the characteristics of residents have changed significantly with implementation of prospective payment for hospital care of Medicare patients. In addition to the traditional nursing home resident, staff will be expected to respond to the needs of patients who are both more acutely ill and responsive to aggressive rehabilitative efforts as well as to patients who are more critically ill and near death. The implications of these changes for the social work staff of long term care facilities will be discussed. PMID- 3112972 TI - Egyptian anatomy and medicine (3000 BC). PMID- 3112973 TI - The supra-transverse intermetatarsocapital bursa: a description and its relation to painful syndromes of the forefoot. AB - Very many painful syndromes of the forefoot remain without a satisfactory explanation; although this region contains quite specific structures, it has suffered from the application of analogies with disorders of the hand. Among these specific components, the presence of the supra-transverse intermetatarsocapital bursa provides an explanation of such clinical entities as the acute syndrome of the second intermetatarsal space and gives fresh impetus to the debate on the etiopathogenesis of Morton's metatarsalgia. On the basis of 25 dissections, the authors studied the region between the metatarsal heads, confirming the presence of these bursae and specifying their site and size and particularly their relations with the common plantar digital nerve at its bifurcation into collateral nerves. PMID- 3112974 TI - Anatomic basis of ligamentous control of elevation of the shoulder (reference position of the shoulder joint). AB - The authors describe in detail the position of greatest stability of the shoulder joint. They review the mechanical importance of this position in the overall physiology of the shoulder-girdle and stress the essential role of two articular ligaments of the shoulder joint (the coracohumeral and inferior glenohumeral ligaments) in arrival at this reference position. There thus exists a passive control, of ligamentous origin, of movements of the shoulder-girdle. The position is essential if the shoulder is to benefit from the full range of movement and full stability which it needs in every day functioning. PMID- 3112975 TI - Anatomic basis of the transgluteal approach to the hip. AB - In order to define the technical modalities of the so-called transgluteal approach to the hip, the authors studied the structure and topography of the anatomic features encountered in this approach. The gluteus medius, gluteus minimus and vastus lateralis muscles are anatomically continuous by way of their tendinous fibers. The gluteus minimus muscle winds over the cranial and then anterolateral aspect of the capsule, to which it is bound by fibrous tracts and tendinous expansions; its terminal tendon blends its fibers with the anterior part of the tendon of the gluteus medius and enters into continuity with the superficial tendinous fibers of the anterior part of the vastus lateralis. The zone of junction of the three muscle structures is closely bound to the anterior aspect of greater trochanter. The caudal neurovascular trunk of the space between the gluteus medius and vastus lateralis is situated at a distance of 3 to 5 cm from the greater trochanter. The practical surgical implications are discussed, particularly as regards the methods of dissecting the anterior margin of the transgluteal incision, exposure of the capsule and preservation of the neurovascular pedicle, with reference to concepts published previously in studies elsewhere. PMID- 3112976 TI - Dynamic modifications of the popliteal arterial axis in the sagittal plane during flexion of the knee. AB - The authors have studied, on the basis of purely radiologic data, the modifications of the popliteal arterial axis during flexion of the knee. They note the appearance in the sagittal plane of very marked flexures of the upper part of the artery, while the lower part describes a harmonious curve. These modifications take place between two fixed points: a cranial fixed point, represented by the origin of the descending artery of the knee, and a caudal fixed point represented by the origin of the anterior tibial artery. The pathologic importance of these modifications of the course of the artery should not be underestimated when obtaining revascularization by means of an arterial prosthesis. PMID- 3112977 TI - Microvascularization of the intracranial dura mater. AB - The authors have studied the microvascularization of the intracranial dura mater by microradiographic and histologic examination of 73 injected anatomic specimens. There exists a very abundant superficial arterial plexus which also serves to supply the inner table of the cranial vault. This plexus is continuous, even at the walls of the venous sinuses and the dural septa. The arteries are for the most part tortuous. The veins may be satellites of the arteries or, on the contrary, from a plexiform network passing through crevices in the interior of the dural layer. The walls of these veins consist only of an endothelium to be seen within the fibrous layer of the dura. Often, the arteries compress the venous lumen; this dangerous situation probably explains the frequent occurrence of arteriovenous fistulae of the dura mater, known by the name of dural fistulae. PMID- 3112978 TI - Anatomic factors in the femoral implantation of the Ilizarov external fixator. AB - Ilizarov's method of external fixation with compression or distraction for lesions of the limbs demonstrates new possibilities in osteogenesis. Its performance with double horizontal pinning on several external rings calls for precautions to avoid lesions of the vessels, nerves and joints. This study, based on anatomic sections radiographed after opacification of the arterial system, makes it possible to propose rules for insertion of the pins. Insertion of the anteromedial pins of the thigh should be made 2 cm in front of the line of projection of the femoral artery, between the middle of the inguinal ligament and the posterior margin of the medial condyle. Insertion of the posterolateral thigh pins should be made 2 cm lateral to the line of projection of the sciatic nerve, between the center of the ischiotrochanteric interval, the apex of the popliteal fossa and the posterior aspect of the head of the fibula. PMID- 3112979 TI - Macroscopic study of the adult thymus. AB - The dissection of 48 cadaveric specimens has been compared with operative findings for a review of the shape, size and site of this gland in the adult. The structure of the thymic compartment and the relations of the thymus, particularly with the vessels of the superior mediastinum and the base of the neck, were studied. The relative positions of the inferior parathyroid glands and the thymus were identified, with respect to the influence of this topography on the surgery of these glands. The arterial suply to the thymus, which is still very abundant in the adult, presupposes a functional organ whose physiologic involution is slow. PMID- 3112980 TI - The arterial trunk of the thumb-index digital collaterals. AB - This is a study of the origin of the palmar collateral arteries of the thumb and radial side of the index finger. The different patterns of the main trunk, the first palmar interosseous artery, in the commissure are discussed, together with the relations of its branches with those of the superficial palmar arch and its relations with the accessory fasciculi of the adductor pollicis and first dorsal interosseous muscles. PMID- 3112981 TI - Influence of the erect posture on the development of the lumbosacral region. A comparative study on the lumbosacral junction of the monkey, dog, rabbit and rat. AB - An animal study was carried out to gain better understanding on the effect of erect posture in the development of the lumbosacral junction. Rhesus monkeys which are able to sit in an upright position were compared with quadrupeds, including rats, rabbits and dogs, whose lumbosacral spines are normally more or less horizontal. The important finding was the presence of the iliolumbar ligament in the rhesus monkey which attached to the last, occasionally the second last, lumbar transverse process and the adjacent iliac wing. A similar ligament was absent in the quadrupeds. We postulate that the stresses created across the lumbosacral junction as a result of the erect posture in the rhesus monkey have played an important role in stimulating the formation of this ligament. PMID- 3112982 TI - Successful extended cardiopulmonary preservation in the autoperfused working heart-lung preparation. AB - Myocardial and pulmonary preservation can be prolonged in the autoperfused working heart-lung (AWHL) preparation by metabolic substrate enhancement. However, uncontrolled pulmonary hypertension following denervation may result in extensive lung injury and occasional early failure of the preparation. To determine whether cardiopulmonary preservation could be reliably extended without development of pulmonary hypertension, six heart-lung blocks were harvested from calves, placed in a normothermic AWHL circuit, and studied. Continuous infusions of isoproterenol and dextrose/insulin were administered for the duration of the preparation. Thirteen heart-lung preparations received neither isoproterenol nor metabolic substrate and served as controls. Myocardial function was assessed by sonomicrometric techniques and pulmonary preservation was evaluated by extravascular lung water, arterial oxygenation on 100% inspired oxygen, static lung compliance, and pulmonary vascular resistance. Pulmonary hypertension developed in the control group and these animals did not survive beyond 7.5 hours. The addition of isoproterenol and metabolic substrate increased organ survival from 4.8 +/- 0.4 to 18.0 +/- 1.4 hours (p = 0.0001) and significantly reduced postexplant pulmonary vasoconstriction (p less than 0.05). Addition of isoproterenol and metabolic substrate to the AWHL model prolonged support of cardiorespiratory function and provided a reliable method for distant procurement in heart-lung transplantation. PMID- 3112983 TI - Patency of laser-assisted anastomoses in small vessels: one-year follow-up. AB - Laser-assisted arterial anastomoses can now be performed with satisfactory short term patency. This study was undertaken to evaluate patency and aneurysm formation with a 1-year follow-up. A microscopically guided CO2 laser was used to anastomose 1.5 to 2.0 mm carotid arteries in 24 rabbits. Under X6 to X40 magnification, 60 to 70 mW were delivered with a spot size of approximately 0.32 mm. One carotid artery underwent laser anastomosis; the opposite served as a sutured control (10-0 nylon sutures). The 48 end-to-end anastomoses were evaluated for patency and aneurysm formation at 3, 6, and 12 months. Aneurysms were defined as a 1.5 times increase in diameter at the anastomotic site. The vessels underwent microscopic examination. All laser-assisted and sutured anastomoses were patent up to 1 year. At 3 months, one of eight sutured and one of eight laser anastomoses were aneurysmal; stenosis was noted in one laser anastomosis. At 6 months, one of eight laser and 0 of eight sutured anastomoses were aneurysmal. At 12 months, one of eight rabbits had died; of the remaining seven, three of seven laser and zero of seven sutured anastomoses were aneurysmal. In total, five of 23 (21.7%) aneurysms developed with the laser technique and one of 23 (4.3%) with the suture technique (p less than 0.05). Laser-assisted anastomoses are technically feasible, and patency at 1 year is equal to those performed with the suture technique. Aneurysm formation is a consistent problem that demands further investigation. PMID- 3112984 TI - Successful treatment of adult respiratory distress syndrome by histamine and prostaglandin blockade in a porcine Pseudomonas model. AB - Porcine Pseudomonas adult respiratory distress syndrome (ARDS) has been shown to respond to combination therapy of 150 mg of cimetidine, 12.5 mg/kg of ibuprofen, 10 mg/kg of diphenhydramine, 0.2 mg/kg of ketanserin, and 30 mg/kg of methylprednisolone (CIDKM or Poly-5) given at 20 and 120 minutes after the onset of a continuous infusion of liver Pseudomonas aeruginosa, 5 X 10(8) colony forming units (CFU) ml at 0.3 ml/20 kg/min. The present study was designed to determine the minimal, effective therapy by selective deletion of individual agents from CIDKM. Eight groups were studied: saline control (S, n = 9), Pseudomonas control (P, n = 8), and the following Pseudomonas plus treatment groups (each n = 5): CIDKM (cimetidine, ibuprofen, diphenhydramine, and ketanserin), CID (cimetidine, ibuprofen, and diphenhydramine), IC (ibuprofen and cimetidine), ID (ibuprofen and diphenhydramine), and CD (cimetidine and diphenhydramine). Pseudomonas alone produced severe ARDS with significant (p less than .05) decreases in PAO2 cardiac index, and systemic arterial pressure and significant increases in pulmonary artery pressure, extravascular lung water (EVLW) and scintigraphically determined pulmonary albumin flux measured as slope index (SI). Full therapy, CIDKM or Poly-5, showed significant improvement in all parameters. Deletion of methylprednisolone did not significantly effect any parameter measured. The deletion of ketanserin, leaving CID, did not alter treatment efficacy, except for a significant decline in cardiac index at 3 hours. Deletion of ibuprofen from CID resulted in a failure to reverse pulmonary arterial hypertension, hypoxemia, elevated EVLW, and increased SI. Removal of either cimetidine or diphenhydramine from CID resulted in significant increases in EVLW compared with control levels and SI compared with both control levels and CID. These results indicate that a combination of both histamine H1 and H2 receptor blockers and the cyclooxygenase inhibitor, ibuprofen, is effective and essential in the treatment of hypoxemia, early pulmonary hypertension, and pulmonary microvascular injury in this fulminant model of porcine Pseudomonas ARDS. PMID- 3112986 TI - [Hospitals' long-term care patients--hidden need for rehabilitation beds?]. PMID- 3112985 TI - Acivicin reduces tumor growth during total parenteral nutrition (TPN). AB - Glutamine appears to be an important substrate for tumor growth. Since tumor growth rate may be stimulated by total parenteral nutrition (TPN), we investigated the effect of the glutamine antimetabolite, acivicin, on methylcholanthrene sarcoma growth in rats maintained on TPN or on rat chow. Acivicin treatment significantly reduced tumor growth by 67% in rats receiving TPN and by 71% in rats maintained on chow. Carcass weights were significantly increased by TPN in both acivicin-treated and saline solution-treated tumor bearing rats. Tumor-carcass ratios were significantly decreased in both groups of acivicin-treated tumor-bearing rats. Acivicin treatment or a similar approach may therefore be useful for stabilizing tumor growth in patients receiving TPN. PMID- 3112987 TI - [Nutrition and plasma apoproteins B and A-I]. PMID- 3112988 TI - [Treatment of patients with infection-dependent bronchial asthma by conservative pulsed irrigation of the bronchi in fiber bronchoscopy with intal and heparin solutions]. AB - The authors presented the results of treatment of 115 patients with infection dependent bronchial asthma. The most noticeable effect was observed in the patients on combined therapy including impulse irrigation of the bronchi (during sparing fibrobronchoscopy) with intal and heparin solutions as compared to the controls receiving this procedure with heparin solution (without intal) and a group of patients who had received intal inhalation by a routine method. A positive therapeutic effect was observed earlier in the patients receiving therapeutic bronchofibroscopy with heparin solution than in patients whose combined therapy included bronchoscopic sanation with nitrofurazone solution. The efficacy of the use of impulse irrigation of the bronchi (in sparing fibrobronchoscopy) with intal and heparin solutions in infection-dependent bronchial asthma was emphasized by the authors. PMID- 3112989 TI - [Sterility in the female. CO2 pertubation]. PMID- 3112990 TI - [Sterility in the female. Pertubation (Rubin test)]. PMID- 3112992 TI - The effect of thromboxane A2 synthesis inhibitors on platelet aggregation in whole blood. AB - Aggregatory responses to arachidonic acid and collagen in vitro were compared in blood (single platelet counting) and PRP (light aggregometry) from four species. Sensitivity of mouse, rat and rabbit PRP to these agonists was not predictive of respective potency in whole blood, whereas for human platelets, responses in blood did not differ significantly from PRP. Indomethacin (3-300 microM) inhibited arachidonic acid-induced aggregation in each species, and collagen responses in all except mouse. In contrast, the thromboxane synthase inhibitors dazoxiben (3.7-372 microM) and SC 38249 (2.6-260 microM) demonstrated activity only in rabbit and human blood. However, since in many experiments drug efficacy decreased significantly in blood compared to corresponding PRP, the concentrations of each agent necessary to inhibit responses were above those at which selectivity has previously been demonstrated against isolated enzyme preparations or in PRP. A fundamental reappraisal of both the potency and selectivity of these inhibitors in whole blood appears essential before their mechanism of action can be firmly established. PMID- 3112991 TI - Pharmacokinetics of contraceptive steroids in patients with cystic fibrosis. AB - The pharmacokinetics of the commonly used contraceptive steroids ethinyloestradiol and levonorgestrel were investigated after oral and intravenous administration in six women with cystic fibrosis. The results were compared with data obtained from healthy women of similar age. The total body clearance of ethinyloestradiol was significantly higher in the patients with cystic fibrosis (0.61 (SD 0.19) l/h/kg) than in control women (0.32 (0.16) l/h/kg; p less than 0.02). In addition, the oral bioavailability of ethinyloestradiol was greater in women with cystic fibrosis than in controls (76.9% (11.7%) compared with 47.3% (7.5%); p less than 0.001). As a result of these two changes, the area under the plasma concentration--time curve after an oral dose of ethinyloestradiol was similar in patients and controls. The pharmacokinetics of levonorgestrel did not differ significantly between patients with cystic fibrosis and healthy women. The data suggest that women with cystic fibrosis will receive similar contraceptive protection from these steroids as do healthy women. PMID- 3112993 TI - Tissue-type plasminogen activator and streptokinase induce platelet hyperaggregability in the rabbit. AB - The ex vivo aggregability of rabbit platelets was assessed after rabbits were treated in vivo with thrombolytic doses of tissue plasminogen activator (t-PA) or streptokinase (SK). t-PA was evaluated at 2 doses; an effective thrombolytic dose of 10 micrograms/kg/min, i.v. and a higher dose of 30 micrograms/kg/min, i.v.. At both concentrations, ex vivo platelet hyperaggregability was observed when collagen, arachidonic acid or ADP were employed as the aggregating agonists. Significant falls in circulating platelet counts were observed after t-PA infusion. Infusion of SK also resulted in ex vivo platelet hyperaggregation. These data reveal that thrombolytic therapy may result in hyperaggregable platelets which may play a role in reocclusion of successfully recanalized blood vessels. PMID- 3112994 TI - Certain membrane-interacting amphiphiles inhibit aggregation and reverse shape change of rabbit platelets pre-activated with arachidonic acid through dissociation of cytoskeletal assembly. PMID- 3112995 TI - Morphometric analysis of epithelial cells of frog urinary bladder. I. Effect of antidiuretic hormone, calcium ionophore (A23187) and PGE2. AB - Changes in epithelial cell morphology, especially at the apical plasma membrane, are frequently cited as initial evidence for antidiuretic hormone (ADH)-induced increase in membrane permeability. The effects of ADH and agents that alter and modify calcium and prostaglandin concentrations on the morphology and cytology of the epithelial cells of frog (Rana pipiens) urinary bladder are presented using the techniques of transmission and scanning electron microscopy. It was found that, like ADH, calcium ionophore, A23187, produce intense microvilli formation, microfilament mobilization and an increase in the density of granules and membrane associated vesicles, suggesting a prominent role of calcium in these processes. Moreover, our results suggest that these membrane and cytosolic transformations may be mediated in part through prostaglandin formation, as exogenous PGE2 mimicked these effects, and indomethacin, a prostaglandin synthesis inhibitor, attenuated ionophore's effect on luminal cytomorphology. However, unlike ADH, prostaglandins and ionophore inhibit hormonal-induced increase in transepithelial water flow. These results suggest that other components more distal to the luminal membrane, perhaps the basolateral membrane, may be rate-limiting for transepithelial water flow and possibly are regulated by either changes in calcium concentrations or prostaglandins. PMID- 3112996 TI - Time- and dose-dependent responses of brain histamine to intracerebroventricular and intraperitoneal administrations of growth hormone-releasing factor (GRF1-44). AB - Changes in the level of histamine (HA) in rat brain induced by intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administrations of growth hormone-releasing factor (GRF1-44) were studied. HA was determined by high performance liquid chromatography (HPLC) in the anterior hypothalamic region, posterior hypothalamic region, median eminence, adenohypophysis, neurohypophysis, hippocampus and prefrontal cortex. GRF1-44 (1-10 micrograms, i.c.v.) induced significant time- and dose-dependent increases in the concentration of HA in the hypothalamo-hypophyseal system and time-dependent decrease of HA in the hippocampus. In contrast, after i.p. administration of GRF1-44 (10 micrograms) the level of HA in the hypothalamus tended to decrease but the total amount of H 1 receptors in the hypothalamo-hypophyseal system did not change. Circadian variations in the GRF-induced HA and growth hormone responses were also observed, responses being lower in the evening than in the morning. It is concluded that GRF interacts with HA at the central level to optimize the function of the somatotropinergic system. PMID- 3112997 TI - Analysis of B cell dysfunction in patients with common variable immunodeficiency by using recombinant interleukin 2. AB - Recombinant interleukin 2 (RIL2) induces proliferation and differentiation of the Staphylococcus aureus Cowan I (SAC)-activated normal B cells to immunoglobulin (Ig) producting cells. We applied this finding to an analysis of heterogeneity in the differentiation states of B cells in patients with common variable immunodeficiency (CVI). B cells from 5 of 7 patients with CVI were tested for their ability to proliferate under the stimulation of SAC, or SAC and RIL2, and for their differentiation to Ig producing cells in the presence of SAC plus RIL2. The results suggest that the differentiation status of B cells in CVI could be divided into four states based on their responses to SAC and RIL2. In the first state, no B cell proliferation or differentiation was demonstrated in our assays. B cells in the second state showed normal proliferative responses to SAC, but not to SAC plus RIL2, and no differentiation to Ig-secreting cells. The third state showed normal proliferation in response to SAC and SAC plus RIL2, but no differentiation to Ig-secreting cells. The fourth state had a normal proliferation response to SAC and SAC plus RIL2, and normal secretions of IgG and IgM in response to SAC and RIL2. These results show that some B cells in CVI have defects in response to RIL2, and at least in terms of defect of B cells, CVI is heterogeneous. PMID- 3112998 TI - Inhibition in maturation of nascent DNA fragments in cultured mouse FM3A cells after treatment with DNA-damaging agents. AB - The effect of DNA-crosslinking agents (cisplatin and mitomycin C), a DNA intercalating agent (adriamycin) or monofunctional psoralen (4-Met-4', 5' dihydropsoralen plus near-ultraviolet radiation) on DNA replication in cultured mouse FM3A cells was studied by sedimentation of the pulse-labeled DNA in an alkaline sucrose gradient. There was no inhibition of the maturation process of the nascent DNA 1 h after treatment of the cells with cisplatin, mitomycin C or adriamycin. However, this process was inhibited progressively during further incubation for 4 to 16 h without the agents, and accumulation of the nascent DNA fragments was observed. In the case of DNA-crosslinking agents, this inhibition may be correlated with an increase in the number of DNA-crosslinks formed during incubation. However, direct inhibition of maturation was not likely since the number was small, up to 4.9 per 10(9) Da. After treatment of cells with monofunctional psoralen, no inhibition of maturation of the nascent DNA fragments was observed. In all cases, there was no degradation of DNA during incubation. PMID- 3112999 TI - [The project 'Normalized Living' of the 'De Landrijt' nursing home in Eindhoven. Various results of an experiment in psychogeriatric care]. AB - Four experimental nursing home settings have been established by nursing home 'De Landrijt' in Eindhoven, each providing care for 4 or 5 long-stay psychogeriatric patients, in order to create flexible living conditions. Nurses are in overall charge; medical care is not provided on a daily basis, but only when necessary. Daily care is also suited to individual needs and possibilities of the patients. In order to evaluate these innovative nursing home conditions, 41 patients were compared with the same type of patients in conventional long-stay wards. To ensure that during the period of the evaluation the homes received the same types of patients, patients considered to need long-term nursing care were allocated randomly to the experimental and conventional homes. The development in functioning of the two groups was measured with a behaviour observation scale for elderly, the OPG--Observation Psychogeriatrics. The most important improvements for the experimental group are observed with respect to Orientation, Mood and Behavioural Problems, Instrumental Activities of Daily Living and Care provided to other patients. More physical aspects of impairment (for instance Activities of Daily Living, Incontinence and Contact) showed hardly any differences between the two groups. Other findings about the project (financial consequences, transfer to general health care) are briefly discussed. PMID- 3113000 TI - [Recalculation of bed occupancy ratio of short- and long-stay nursing home patients]. AB - The authors present a revised equation by which the ratio of beds occupied by short- and long-term patients can be calculated. In 1984, 8.2% of the beds were occupied by short-stay somatic patients, compared to 2.17% occupied by short-stay psychogeriatric patients, the dividing line between short-stay and long-stay patients being 6 months. These data are also compared with those in 1985. In the latter year a distinction is made between somatic short-stay patients who died, and other somatic short-stay patients. PMID- 3113001 TI - Parasitological evaluation of curative and subcurative doses of 9-acridanone hydrazone drugs against Schistosoma mansoni in baboons, and observations on changes in serum levels of anti-egg antibodies detected by ELISA. AB - Derivatives in the class of 9-acridanone-hydrazones were found to be highly active against Schistosoma mansoni in baboons. Single doses of 25 mg/kg were fully effective. Data are presented showing changes detected by ELISA in antibody levels against schistosome eggs which correlated positively with the effect of chemotherapy. This approach may help to evaluate the effects of treatment of human schistosomiasis where the detection of low egg counts is problematic. PMID- 3113002 TI - The morbidity of schistosomiasis mansoni in Maniema (Zaire). AB - The morbidity of schistosomiasis mansoni was assessed in Makundju (population 547; prevalence 96%, mean egg load 791 epg) and Massimelo (pop. 363; prev. 19%, mean egg load 39 epg), 2 similar villages in the forest zone of Maniema, Zaire. The prevalences of other parasites including malaria (holoendemic) were comparable. "Intermittent diarrhoea" (mostly bloody) was a complaint of 55% and 3% of the populations, respectively, "intermittent abdominal pain" of 63% and 25%, and "fatigue" of 33% and 19%. Enlargement of the left liver lobe was present in 45% and 9% of the populations, right lobe hepatomegaly in 32% and 3%, splenomegaly in 29% and 9%. Hepatomegaly and splenomegaly in Makundju were often very impressive, and most frequent in the 6- to 18-year-old group. Anaemia (haematocrit less than or equal to 35%) was present in 30% and 9% of males and 36% and 21% of females. Mean length and weight were lower in Makundju for boys aged 11 to 18 years. Ergometric results (Astrand cyclometer, male adults only) were comparably low in both villages (mean VO2max. 19.3 and 18.9). Analysis of the data according to egg load within the Makundju community revealed a significant relationship only in the following cases: higher frequencies of diarrhoea, abdominal pain and fatigue in those excreting more than 200 epg compared with those excreting fewer; left lobe splenomegaly gradually increased with egg load in children under 18; in people over 40 it occurred at a higher frequency in those excreting more than 2000 epg than in those excreting fewer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113003 TI - Loss of resistance to reinfection with Schistosoma japonicum in mice after treatment with praziquantel. AB - Seven-week-old adult Schistosoma japonicum worms were eliminated from mice within one week of treatment with praziquantel and oviposition ceased within 2 days. The excretion of faecal eggs ceased within 2 weeks of treatment. The numbers of eggs retained in the intestine and those in the liver remained constant for up to 20 weeks after cure. Untreated, infected mice were on average 80% resistant to reinfection and mice challenged one week after treatment were equally resistant. However, reductions in the ability of mice to resist a challenge were evident as early as 2 weeks after cure (average resistance 40%) and by 5 weeks the resistance had dropped significantly (average resistance 30%) in all experiments. Mice were no longer significantly resistant to challenge 13 weeks after treatment, in 2 out of 3 experiments. It is suggested that the reduced ability of cured mice to resist reinfection is related to the resolution of the granuloma response and associated pathology rather than the loss of tissue eggs. PMID- 3113004 TI - Immunogenetic factors involved in the pathogenesis of distinct clinical manifestations of schistosomiasis japonica in the Philippine population. AB - Immunogenetic factors were studied in 60 patients with schistosomiasis japonica in the Philippines, of whom 15 were characterized by marked hepatosplenic lesions and 45 characterized by cerebral symptoms. Immune responsiveness of the patients to schistosomal antigen was measured by T cell proliferation in vitro, and their HLA-A and -B specificities were typed. All but one hepatosplenic patients showed strong immune responsiveness to the schistosomal antigen, whereas both low and high responders were observed in the cerebral patients. A significant association between HLA-B40 and high responders to the schistosomal antigen was observed (P = 0.0458), and this HLA specificity was increased in frequency in the hepatosplenic patients. HLA-B16 was not observed in the hepatosplenic patients, but was common in the cerebral patients (26.5%) (P = 0.0255), and this HLA specificity was commoner in the low responders than in the high responders. These observations suggest that an HLA-linked gene governs the clinical manifestations of human schistosomiasis japonica by controlling immune responsiveness of the infected hosts to the schistosomal antigen. PMID- 3113005 TI - Immunity after treatment of human schistosomiasis mansoni. III. Long-term effects of treatment and retreatment. AB - Group mean Schistosoma mansoni reinfection patterns are presented for 2 years after treatment with oxamniquine in 1981 of over 100 9- to 16-year-old Kenyan schoolchildren, and for one year after retreatment in 1983 with either oxamniquine or praziquantel when most (nearly 700) infected people in the whole community were treated. Quality control confirmed comparable Kato egg counts throughout the study. Continuing transmission after 1981 raised prevalence to nearly its original level within 6 months, but intensity remained suppressed throughout the 2 year follow-up and very few children reacquired heavy infections (greater than 400 eggs/g). Age and sex had significant effects: reinfection diminished with age, especially among boys--a pattern not apparently attributable to differential water contact. Children with heavy pretreatment infections tended to develop heavy reinfections but this trend was not statistically significant on a group basis, nor were similar trends during the period of less pronounced transmission following the 1983 community treatment. Oxamniquine was equally effective in children receiving it in both 1981 and 1983, and the efficacy of praziquantel resembled that of oxamniquine. In this area of Kenya, repeated chemotherapy will be needed to contain transmission, probably annually or biennially, unless supplemented with other, effective control measures. These findings confirm the beneficial effects of treating even a limited segment of a community at intervals of a year or more without necessarily stopping transmission. They are also compatible with recent findings on potential immune mechanisms in man. PMID- 3113006 TI - Prevalence of renal involvement in Schistosoma japonicum infection. AB - 244 outpatients and 100 hospitalized patients with confirmed Schistosoma japonicum infection were prospectively surveyed for the presence of nephropathy. There was no association between schistosomiasis and renal disease in the outpatient group. Three hospitalized patients had evidence of significant nephropathy, but this number was not significantly higher than in a control group of 100 hospitalized age and sex-matched control patients without schistosomiasis. One schistosomiasis patient with severe nephrotic syndrome underwent percutaneous renal biopsy. Neither S. japonicum antigen nor antibody was found in the biopsy specimen. 64 of the 100 hospitalized patients had portal hypertension; in 28 patients there was hepatic decompensation. Only one of these hepatosplenic patients had evidence of renal disease. Thus renal involvement was uncommon in patients presenting various manifestations of chronic S. japonicum infection, including those with severe hepatosplenic disease. These results contrast markedly with S. mansoni infection, in which nephropathy associated with advanced liver disease is a distinct, well-recognized clinical entity. PMID- 3113007 TI - Density-dependent timing of defaecation by Rhodnius prolixus, and its implications for the transmission of Trypanosoma cruzi. AB - Transmission of Trypanosoma cruzi is crucially dependent on the timing of defaecation by their insect vectors. Experimental studies on Rhodnius prolixus nymphs revealed a negative correlation between blood meal weight and defaecation time. Bugs which fed to repletion defaecated on average 7 min after feeding, whereas bugs with interrupted feeds defaecated about 1 h later. As blood meal weight of triatomine bugs is density-dependent, these results suggest that the greatest risk of successful T. cruzi transmission would occur in recently colonized houses where the bug population is still increasing, or in houses recolonized after a vector control attempt. PMID- 3113009 TI - Preoperative nutritional evaluation and support for liver transplantation in children. PMID- 3113008 TI - Report of an independent evaluation mission on the National Bilharzia Control Program, Egypt, 1985 (abridged version). PMID- 3113010 TI - Expansion of a large granular lymphocyte subset that lacks natural killer activity in long-term kidney transplant recipients. PMID- 3113011 TI - Isolation of islets of Langerhans following cold storage of human pancreas. PMID- 3113012 TI - The isolation and purification of human pancreatic islets. PMID- 3113013 TI - Cryopreservation purifies canine pancreatic microfragments. PMID- 3113014 TI - Aspects of pediatric intensive care after liver transplantation. PMID- 3113015 TI - Effect of OKT3 on survival and rate of retransplantation. PMID- 3113016 TI - The effect of multiple-organ donation on the degree of preservation of isolated pancreas islets. PMID- 3113017 TI - Liver free fatty acid accumulation as an indicator of ischemic injury during simple, cold, ischemic preservation and the effects of oxygen. PMID- 3113018 TI - Leukocyte binding and Ia-expression in vascular endothelium. PMID- 3113019 TI - Gonadal steroids in cardiac atherosclerosis in primates. PMID- 3113020 TI - [Changes in the number of sister chromatid exchanges in cultured Chinese hamster cells with limited proliferation. Additional studies]. AB - During "stationary phase ageing" of cultured Chinese hamster cells (B11dii-FAF28 line, 2372a clone), i. e. while decreasing the proliferation rate and in the stationary growth phase the frequency of spontaneous sister chromatid exchanges (SCE) progressively increases (from 2- to 23-day "age"); the frequency of thiophosphamide-induced (1h) SCE increases from 2- to 23-day "age" by the same value as the frequency of spontaneous SCE; the cells deepen into the R-phase of the cell cycle. PMID- 3113021 TI - Farber's disease: a fine structural study. AB - A 1-week-old baby boy presented with hepatosplenomegaly, coarse facial features, and cloudy corneas. A metabolic storage disease was considered and he underwent cutaneous and liver biopsy. By light microscopy the skin was normal. Kupffer cells were enlarged and had foamy cytoplasm. Ultrastructural examination of skin and liver demonstrated features compatible with Farber's disease: curvilinear and "banana" bodies, zebra-like structures, and concentric lamellar bodies. A deficiency of lysosomal acid ceramidase was subsequently demonstrated in cultured fibroblasts and in liver tissue corroborating the ultrastructural findings. PMID- 3113022 TI - Periosteal epithelioid hemangioendothelioma with leptomeric fibrils. AB - A case of recurrent periosteal epithelioid hemangioendothelioma of the right femur in a 66-year-old woman is reported. Microscopic examination showed epithelioid tumor cells with frequent intracytoplasmic vacuoles arranged in small nests or cords in hyalinized stroma. Immuno- and lectin-histochemical studies for factor VIII-related antigen and ulex europaeus I lectin indicated the endothelial nature of the tumor cells. Ultrastructurally, a few tumor cells contained leptomeric fibrils and crystalline filamentous aggregates in addition to showing certain features of endothelial cells. There seems to be no previous report of a vascular tumor containing leptomeric fibrils, which are often noted in normal striated muscle cells and their tumors. The bland appearance of the epithelioid tumor cells, poor vasoformative nature and prolonged clinical course differentiated this tumor from conventional angiosarcoma and so-called hemangioendothelioma of bone. PMID- 3113023 TI - Normal non-neoplastic plasma cells have not been seen to form desmosomes. PMID- 3113024 TI - Seminal plasma levels of fucosyltransferase, galactosyltransferase and sialyltransferase in normospermic and oligospermic men. AB - The activities of fucosyltransferase, galactosyltransferase, and sialyltransferase were estimated in ultracentrifuged seminal plasma samples from normospermic and oligospermic men. There was no significant difference with regard to these activities between the two groups. Hence, fucosyltransferase activity was high in both normospermic (mean value: 190.2 nmol/l) and oligospermic men (mean value: 157.2 nmol/l) and exceeded that of blood plasma (mean value: 7.6 nmol/l) by 20-25 times. On the contrary, the activity ratio between seminal plasma and blood plasma of galactosyltransferase and sialyltransferase was low and fairly close to 1. A significant correlation was noted between seminal plasma galactosyltransferase activity and semen volume only in normospermic men. Significant inverse correlations in oligospermic men were observed between seminal plasma sialyltransferase activity and sperm concentration (and total sperm count) as well as between galactosyltransferase and fucosyltransferase activities. PMID- 3113025 TI - Medical treatment of idiopathic infertility. AB - We conclude that, although many therapies have been advocated, no regimen has proved to be consistently effective in the treatment of idiopathic male infertility. Couples in which the husband is identified as having idiopathic infertility should be advised of the inconsistent and often low conception rates obtained with medical therapy. This should be weighed against the possibility of greater success with in vitro fertilization and the likelihood of success with artificial insemination by donor. Matson and colleagues performed in vitro fertilization on 75 couples in which the husband was oligospermic. When the husband was moderately (5.1 to 11.9 million motile sperm per milliliter) or severely (less than or equal to 5 million motile sperm per milliliter) oligospermic, fertilization rates were 56 and 30 per cent, respectively. This is in comparison to a fertilization rate of 72 per cent in normospermic couples. Following embryo transfer, pregnancy rates were similar in all groups. In vitro fertilization, although expensive and often not covered by insurance policies, may yield results in 1 month. Pharmacologic treatment of the male, which is less expensive, requires several months before improvement might be expected. The decision as to which course to recommend should be made after careful consultation with the couple. If empiric therapy is decided upon, the choice of an agent is somewhat arbitrary. Reasonable initial choices for the oligospermic patient are tamoxifen (or clomiphene citrate) or HCG (HCG may also be used in the patient with idiopathic asthenospermia). Testosterone rebound, with its risk of permanent azoospermia, is not an acceptable initial therapy. Similarly, the results of studies of testolactone, GnRH, pentoxifylline, and kallikrein either demonstrate low pregnancy rates or are too preliminary to recommend at this time. Regardless of the choice of therapy, it should be administered for at least 3 months to include the length of one spermatogenic cycle. The performance of randomized, double-blind, placebo-controlled, cross-over studies of present and future treatments will allow more definite conclusions to be drawn. PMID- 3113026 TI - Endocrine investigation and therapy. AB - The most commonly investigated testicular disorder is male infertility. Although endocrine causes are uncommon, they are potentially curable. A careful history and examination for subtle features of hypogonadism are important initiating steps. Understanding the appropriate use of both baseline and dynamic testing of the hypothalamic-pituitary-gonadal axis (and, in certain instances, the adrenal and thyroid glands) is extremely important. PMID- 3113028 TI - [Superovulation and uterine lavage in relation to subsequent conception in donor cows]. AB - On the Slusovice co-operative farm, embryo transfer has been practised since 1984 as a method of controlled reproduction of the heifer and cow herd. The effect of superovulation, embryo recovery and administration of 500 micrograms Oestrophan Spofa upon the donors' conception rate and upon their resuming a new reproduction cycle was studied on this farm. The effect of superovulation, induced by FSH-P (Folicotropin, Spofa), was evaluated in 162 cows, out of which 121 (74.69%) got in calf after three inseminations. Fifty-nine (48.76%) of the pregnant cows got in calf after the first insemination, 38 (31.40%) after the second insemination, and 24 (19.83%) after the third insemination. Having been subjected to embryo collection and luteolysis, the donors conceived within 67.6 days, on an average, and the animals superovulated within 60 days post partum conceived within 59.11 days. The average SP of the superovulated animals was about 148 days but in the donors from which the embryos had been recovered within 60 postpartal days the SP did not exceed 110 days. Hence the earlier postpartal superovulation of cycling cows speeds up the resumption of reproduction in the donors and increases the numbers of recovered embryos. Repeated superovulation had no influence on the fertility of the cows but adequately prolonged the service period. PMID- 3113029 TI - [The effect of monensin on rumen fermentation and weight gain in bulls fed a diet containing nontraditional feed]. AB - Two groups of bullocks, each consisting of 125 animals, were subjected to a trial to study the effect of monensin (Rumensin premix) administered at doses from 125 to 175 mg per head/day on rumen fermentation and weight gains. For 135 days the animals were given a diet based on green juicy forage with a supplement of chopped straw and concentrate mixture; this mixture contained 20-30% of dried poultry droppings. In the experimental group with monensin, the concentration of total and protein nitrogen and the molar percentage of propionic acid significantly increased (23.7 and 28.5%, respectively, P less than 0.01) and the acetate: propionate ratio decreased four hours after feeding. Further, the energy yield of the production by volatile fatty acids (VFA) significantly increased in the rumen contents (76.89%, 78.64%, respectively, P less than 0.05). The levels of ammonia and non-protein nitrogen were not affected by the addition of monensin. The average daily live weight gains were 713 g in the control group and 800 g in the experimental group; this means that the gains of the experimental animals rose by 12.2%. Monensin had a positive influence on the proportions of the rumen-produced VFA in favour of propionic acid which, in turn, favourably influenced the energy balance of nutrient conversion and efficiency. PMID- 3113027 TI - Comprehensive care of the patient with gut failure: present and future. PMID- 3113030 TI - [Determination of the inhibitory effect of a biologically active preparation on the reproduction of micro-organisms from the intestines of ruminants]. AB - A procedure for the production of biologically active substances from pine and spruce needles was worked out within the research project Utilization of Tree Verdure. The product was referred to as a biologically active preparation. The fields of its possible uses include agriculture (animal production-feeding), cosmetics (production of pastes, soaps, etc.), pharmaceutical industry (after additional conditioning the product can be used for manufacturing medicinal drugs for the control of inflammatory diseases and the like). The biologically active preparation, i. e. the pine needle extract, was studied as to its effect on some of the most numerous microorganisms in the intestines of ruminants. As found, this preparation has a partial inhibitive action on the growth and reproduction of microorganisms. The biologically active preparation is an extract isolated from the needles by means of 0.3% sodium hydroxide. Besides extractive substances it also contains the residues of organellae of cellular nature (which got into the extract through the filter during the process of preparation) and a small amount of fibre (0.33%). The chemical composition of the biologically active preparation is varied: until now about 220 substances, many of which are biologically active, have been found to be present in the product. PMID- 3113031 TI - [Migration of protoplasmic droplets and phagocytosis of damaged sperm during their passage through the efferent ducts in boars and bulls]. AB - Seventeen gonad pairs of boars and ten gonad pairs of bulls were examined to evaluate the migration of protoplasmic droplets and the phagocytosis of defective spermatozoa. The material for a microscopic investigation of secretions was collected from two sites in the testis and from seven sites in the epididymis. The greatest motion of protoplasmic droplets was recorded in the caput epididymidis, although the migration of droplets from the proximal section of the connective part of the flagellum towards the distal parts could also be observed as far as in the cauda epididymidis in both animals. A proximally located droplet still occurred in the cauda epididymidis in 4.5% of the spermatozoa of boars and in 1.9% of those of bulls. Absent mitochondrial spirals or swollen connective parts were observed in the imprints of testicular tissue in almost 50% of the spermatozoa whereas in the secretion of efferent ducts they were observed only in 0.3% of bull spermatozoa and about 3% of boar spermatozoa. No such defects were recorded in the epididymis head and tail in either of the two species. The marked reduction in the number of defective spermatozoa without mitochondrial spirals in the secretion of efferent ducts and after passage through the caput epididymidis testifies to the phagocytic ability of the epithelium of this part of efferent ducts. PMID- 3113032 TI - [Decrease in the milk yield in cows casued by dipterous blood-sucking insects and the protection of heifers with Oxamate, a repellent, in the area of Leningrad]. AB - Blood-sucking dipterous insects, milk yield losses caused by these insects to cows in the pasture and the possibilities of cattle protection against these insects were investigated in the Leningrad region of the USSR in 1982-1984. The invasion by horse-flies causes the greatest trouble to grazing cattle. Twenty five horse-fly species were identified during the study. The nine prevailing species constituted more than 85% of the horse-flies invading the animals. The horse-flies flew for 50-55 days from the beginning of June to the beginning of August; mass flights were observed for two weeks starting in the second decade of June. A twelve-hour repelling action was recorded in the Oxamate repellent applied as 20% emulsion. A new portable motor-powered aerosol sprayer was tested during the study. The losses in milk yields caused by horse-flies in the Leningrad region were computed; in the period of the horse-fly flights the milk yields are reduced by 13%. The economic benefit of the treatment of the animals with the Oxamate repellent was 9.11 roubles per rouble invested. Manitoba-type traps attracting the horse-flies to an optical bait (a black ball or cube) were used as an additional method of reducing the occurrence of horse-flies in the pasture. PMID- 3113033 TI - [Use of sheep erythrocytes and plasma for the determination of neuroparalytic substances in vitro]. AB - A simple method of the determination of nerve-paralytic substances is presented, based on the use of ram erythrocytes and plasma with the determination of cholinesterase inhibition. Dichlorvos administered at the rate of 94.64 ng per litre induced 50% inhibition of acetylcholinesterase in the erythrocytes; administration of dichlorvos at the rate of 243.82 ng per litre caused a 50% inhibition of butyrylcholinesterase in the plasma. PMID- 3113034 TI - [The effect of water depletion on renal excretion of urea and electrolytes in sheep]. AB - Experiments were conducted with the sheep of Merino breed given water only at a rate corresponding to 0.5% of their live weight for three days. The animals were given feed ad libitum and during the control measurements water was also available to them ad lib. The fourth day the sheep were given no water and no feed and their renal functions were measured by the standard clearance technique. In the water-depleted sheep the diuresis was naturally reduced and the glomerular filtration rate (GFR) was also observed to have decreased from 77.6 +/- 5.3 to 62.2 +/- 4.2 ml X min-1, P less than 0.05. A small, though significant, decrease was also recorded in plasma urea concentration as a result of the reduced intake of food. The amount of excreted urea decreased by 41% (from 354.0 +/- 41.6 to 208.5 +/- 25.5 mumol X min-1, P less than 0.01) without significant changes in fractional excretion and tubular reabsorption of urea. After three days of water depletion the sheep exhibited a tendency of slight natriuresis whereas the excretion of potassium was reduced. Water depletion was also accompanied by a significant increase in the osmolality of plasma (from 298.0 +/- 1.3 to 317.0 +/- 1.8 mosmol X kg-1 H2O, P less than 0.001) and urine from 789.0 +/- 95.0 to 1547.0 +/- 53.0 mosmol X kg-1 H2O, P less than 0.001), without changes in the clearance of free water. On the other hand, the osmotic clearance was reduced as a result of suppressed excretion of urea and potassium (from 2.33 +/- 0.21 to 1.61 +/- 0.17 ml X min-1, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113035 TI - [The first finding of Paramphistomum daubneyi (Dinnik, 1962) in beef cattle in Algeria]. AB - The first finding of the causative agent of paramphistomatosis of cattle in the coastal region of Algeria is described. As found on the basis of histological diagnosis, this causative agent is the species Paramphistomum daubneyi (Dinnik, 1962). Lymnaea truncatula was found to be present as a potential intermediate host at the localities where the cattle harbouring these trematodes were kept. It is suggested by the high intensity of invasion by the trematodes (up to 2204 specimens in one host) that the animals suffered from severe helminthosis in some cases. The finding of the causative agent of bovine paramphistomatosis in Algeria draws attention to the need of further investigation of trematodosis in the cattle kept in that country. PMID- 3113036 TI - Close relationship between TRT virus isolates. PMID- 3113037 TI - Porcine torovirus? PMID- 3113038 TI - Differentiation of Brucella abortus and Yersinia enterocolitica serotype 09 infections in cattle: the use of specific lymphocyte transformation and brucellin skin tests. AB - The lymphocyte transformation test (using an in vitro whole-blood lymphocyte stimulation procedure) and the Brucellin skin test were applied to five heifers infected with virulent Brucella abortus strain 544, five cows inoculated with Yersinia enterocolitica serotype 09, and four non-exposed cows. Lymphocytes from Brucella-inoculated animals persistently gave very high blastogenic reactions indicative of active Brucella infection. The test was persistently negative in Yersinia-infected and non-exposed cattle. Four of the five cows infected with Yersinia enterocolitica type 09 and all four control cattle were persistently negative to the delayed hypersensitivity skin reaction with brucellin. All cattle infected with Yersinia enterocolitica type 09 were strongly positive to the Rose Bengal, Serum agglutination, Complement fixation and Antibovine globulin tests using Brucella abortus antigens. One lactating cow infected with Yersinia enterocolitica type 09 was positive to Brucella milk ring test. These results indicate that standard Brucella serological tests are unreliable in differentiating the two infections in cattle and that both the Lymphocyte transformation and brucellin skin tests could be used to differentiate bovine brucellosis from yersiniosis. PMID- 3113039 TI - Comparative pathogenicity of Theileria annulata strains. AB - Twenty three susceptible crossbred calves were inoculated with five Indian strains of Theileria annulata, collected from natural cases of tropical theileriosis at Ludhiana, Hissar, Jaipur, Uruli-Kanchan and Bangalore. All the strains produced clinical disease with typical symptoms and lesions of acute theileriosis. The strains were considered highly virulent and equally pathogenic. PMID- 3113040 TI - The prevalence and identity of Sarcocystis in beef cattle in New Zealand. AB - Muscle tissue from the oesophagus and diaphragm of 500 beef cattle slaughtered in New Zealand was examined for Sarcocystis infection by microscopic examination of cysts isolated from muscle samples. All cattle were infected with Sarcocystis; based on light microscopy of cysts, 98% had thin-walled Sarcocystis cruzi cysts and 79.8% had thick-walled (Sarcocystis hirsuta/Sarcocystis hominis) cysts. Cysts were also collected for electron microscopy and transmission experiments. Thick walled cysts could not be distinguished as S. hirsuta or S. hominis by light or electron microscopy. Thick-walled cysts were fed to three cats and one human volunteer; one cat shed sporocysts but not the human volunteer. Electron microscopy of the cysts revealed many features that have not been described previously. PMID- 3113041 TI - Immunization of neonatal bovines against Theileria annulata by an infection and treatment method. AB - Sixty three cross-bred (Bos taurus X Bos indicus) 4-5-day-old calves were divided into 16 groups (A-P). Each calf in Groups A and B was given ground-up-tick supernate prepared from Theileria annulata-infected or non-infected Hyalomma anatolicum anatolicum (GUTS) equivalent to 5 ticks (50 infected acini). Groups D and E received infected GUTS equivalent to 2 ticks (20 infected acini) and Groups G and H were given infected GUTS equivalent to 1 tick (10 infected acini). Each calf in Groups J, K and L received infected GUTS equivalent to 5 infected acini (0.035 tick), and Group O was inoculated with non-infected GUTS equivalent to 5 ticks. Each calf in Groups A, D, G, J, K and O was also given a single intramuscular injection of long acting oxytetracycline, 20 mg kg-1 body weight just after inoculation of GUTS. Severe reactions resulted in the death of five of eight, three of eight, five of six, one of five and one of five calves in Groups A, D, G, J and K respectively and all of the calves in Groups B, E, H, and L. The surviving calves of Groups A, D, G, J, K and O were challenged on Day 45 post immunization along with freshly introduced susceptible control calves of Groups C, F, I, M, N and P. All the calves of Groups A, G, J and K withstood the challenge dose; in Group D four of five and in Groups C, F, I, M, N, O, and P all the calves died of theileriosis. It is concluded that though the infection and treatment method of immunization may be used for neonatal bovines, the dose of immunogen should be based on actual counts of infected salivary acini of ticks instead of the number of ticks. PMID- 3113042 TI - In vitro hatching of the infective eggs of Ascaridia galli in tissue extracts. AB - Extracts of proventriculus (PE) and small intestine (IE) of fowl were used, for the first time, as media for the in vitro hatching of infective eggs of Ascaridia galli. Hatching was successful in a mixture of equal parts of PE and IE (MIP) under normal air and under different concentrations of CO2, but not under 100% CO2. A very highly significant retardation (P less than 0.001) in the rate of hatching appeared as the concentration of CO2 was increased, indicating that high levels of CO2 inhibit the process of hatching. 100% of the eggs hatched in PE in 40.5 min whereas they did not hatch at all in IE, suggesting that IE alone has no influence on egg hatching. The shortest time taken for 100% of the eggs to hatch in this study suggests that the present method of hatching is faster than all previous methods used by different workers. PMID- 3113043 TI - Simulation of fly-waves to assess the ability of diflubenzuron to protect sheep against flystrike by Lucilia cuprina. AB - Sheep were exposed to mass-released gravid females of the sheep blowfly, Lucilia cuprina, in a fly-proof animal house at various times after treatment with the insecticide diflubenzuron (1000, 1500 and 2500 ppm a.i.). Untreated sheep were similarly exposed as controls, while sheep treated with either diazinon (400 ppm a.i.) or cyromazine (1000 ppm) were used as standards for comparison. Before exposure, groups of sheep were wetted by simulating rainfall in the animal house in order to increase their susceptibility to flystrike by L. cuprina. In one trial, sheep jetted with either diflubenzuron or cyromazine (both at 1000 ppm) were protected against flystrike for at least 110 days. At 1500 ppm, diflubenzuron performed significantly better with no bodystrike occurring in the group until the end of the trial at 170 days. Under more severe fly pressure in a second trial diflubenzuron at concentrations up to 2500 ppm provided the same protection as diazinon (approximately 56 days), but performed significantly better thereafter. No cross-resistance to diflubenzuron was found in diazinon resistant field populations of L. cuprina in laboratory bioassays. The data show that diflubenzuron would be suitable as a prophylactic treatment for flystrike. PMID- 3113044 TI - Coccidiosis in swine. PMID- 3113045 TI - [Morphological changes in broilers produced by feeding antibiotics]. AB - Morphologic studies were carried out on the liver, kidneys, and small intestine of broiler birds that had been given antibiotics with the feed (virginiamycin, 20.0 ppm, flavomycin, 4.8 ppm, and avotan, 10.0 ppm) in the course of 49 days, kept with a group of controls. The liver of the test birds showed protein and fatty dystrophy, and the kidneys--protein dystrophy. The small intestine showed thinning of the wall and increase in the villi intestinales length. The manifestation of the morphologic changes depended on the amount of the antibiotic taken in. Those of the birds that were offered flavomycin had well manifested lesions, while in birds that were given virginiamycin and avotan only the lesions were more slightly expressed. PMID- 3113046 TI - [Superovulation induction in buffalo cows (Bubalus bubalis) with follicle stimulating hormone (FSH)]. AB - A total of 19 buffalo cows were used to induce superovulation following a pattern that included the use of FSH at the rate of 40 mg in the course of four days, applied twice a day and of Oestrophan at 48 hours after the beginning of treatment. Fifteen animals manifested estrus and were twice inseminated. The superovulation response of the ovaries was 4.3 +/- 0.8 yellow bodies and 0.5 +/- 0.24 follicles greater than 8 mm. A nonsurgical method was employed to obtain 24 embryos of high quality and an unfertilized ovum from 8 buffalo cows. PMID- 3113048 TI - [Professional and scientific aspects of the activities of the Union of Societies of the Medical Sciences--paramedical personnel in the Cluj-Napoca Oncology Institute]. PMID- 3113047 TI - [A rare case of Sarcocystis encephalitis in a sheep]. AB - Microbiologic, serologic, and fecal investigations were carried out with a flock of sheep to explore the spontaneous setting in of a disease with nervous signs in a sheep. The animal was forced to be slaughtered, and portions of the viscera and the brain were studied histopathologically. The presence of toxoplasmosis was ruled out via investigations of blood sera taken from weaned lambs and from ewes that had miscarried in the same flock, employing the microprecipitation test in agar gel after Hubner and Uhlikova. The microbiologic studies did not reveal any infection of contagious character, and routine parasitologic studies ruled out the presence of Coenurus cerebralis and of Oestrus ovis larvae. Studies of the brain of a sheep revealed the presence of sarcocysts in the hemispheres, with changes characteristic of nonsuppurative encephalitis. PMID- 3113049 TI - [Recuperative therapy in posttraumatic diseases]. PMID- 3113050 TI - [Clinico-radiological aspects of the Pancoast-Tobias syndrome]. PMID- 3113051 TI - [The academic and professional orientation of students. The contribution of the physician and paramedical personnel in the school medical office]. PMID- 3113052 TI - [Practical evaluation of human biorhythms]. PMID- 3113053 TI - [First and principles in caring for the comatose child]. PMID- 3113054 TI - [Psychosocial study of the estimable blood donor]. PMID- 3113055 TI - [Implications of health education research in the health culture dynamics of textile workers and the role of paramedical personnel]. PMID- 3113056 TI - [Centenary of the birth of Dr. Calin Ottoi]. PMID- 3113057 TI - [What and how much do adolescents know about the rearing, care and health protection of small children]. PMID- 3113058 TI - [Comas in drug poisonings]. PMID- 3113059 TI - [General principles of caring for comatose children with multiple injuries]. PMID- 3113060 TI - [Attitude of paramedical personnel to medical assistance and emergency transport in acute myocardial infarct]. PMID- 3113061 TI - [Role of paramedical personnel in applying preventive measures and controlling endemic goiter]. PMID- 3113062 TI - [Health education about a hygienic regimen for the life style, studying and leisure of schoolchildren]. PMID- 3113063 TI - Melanoma in situ (MIS) adjacent to an invasive nodular melanoma ("SSM/NM") and its metastases--DNA-cytophotometry, mitotic index, and anisokaryosis. AB - Malignant melanomas of the superficial spreading type usually have an intraepidermal tumour component in their periphery which frequently displays the morphological features of a melanoma in situ (adjacent MIS). It is thus comparable to exclusively epidermal melanomas; melanoma in situ (MIS). Taking 10 superficial melanomas with a nodular component ("SSM/NM") 31 adjacent MIS regions and 36 nodular melanoma components were analysed in serial tissue slides. Planimetric estimation of the nuclear areas was employed as a measure of anisokaryosis. DNA-Feulgen-cytophotometry was applied to obtain an objective variable in judging malignancy in the DNA-histographs (paraffin material). Furthermore we investigated 8 metastases of one of the malignant melanomas applying the methods described. A comparison of the epidermal with the invasive tumour components revealed an increase in the nuclear area which, however, decrease from the superior to the inferior nodular regions and which are further reduced in melanoma metastases. Anisokaryosis is evidently less in metastases compared with all primary melanomas. The nuclear DNA-content increases from the epidermal to the invasive tumour compartments and is lower in the inferior nodular regions when compared with the superior ones. No further significant differences are, however, established in the metastases. The coefficients of variability of the DNA-contents, being a potential indicator of DNA-heterogeneity reflect higher values in the epidermal tumour components compared with the nodular regions, decreasing from the superior to the inferior nodular parts of the tumour. All metastases have smaller values than the respective primary melanoma. In the DNA-histographs 75% of the intraepidermal tumour components have obvious signs of malignancy including tumour cell stem lines in 19% of the cases. 85% of the nodular regions investigated have clear signs of malignancy, 33% of which also have aneuploid stem lines. All metastases have obvious signs of malignancy and tumour cell stem lines in 50% of the cases observed. The following conclusions can be drawn from our findings: DNA-Feulgen-cytophotometry and nuclear planimetry are additional feasible methods for judging the epidermal component of a melanocytic lesion as malignant (adjacent melanoma in situ) on paraffin material. Furthermore these methods give different results in invasive nodular versus epidermal (in situ) melanoma components. Both the DNA-histographs and our immunohistochemical investigations (monoclonal antibody P 3.58) indicate the malignant potential of adjacent MIS.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3113064 TI - The role of microvascular environment in the metastasizing ability of an experimental tumor. AB - A rapidly growing, locally very invasive and easily transplantable fibrosarcoma that was developed through chemical carcinogenesis in Balb/c mice in this laboratory several years ago did not metastasize into the viscera of its hosts when implanted into the subcutaneous connective tissue or skeletal muscle of syngeneic mice. When, however the same tumour was implanted into the liver or the kidneys of Balb/c mice it metastasized extensively into many different organs within 2 weeks of its transplantation. Evidence is presented that because of some unknown deficiency the cells of the fibrosarcoma under study are unable to penetrate through the endothelial wall into the lumen of the particular type of vessels which surround and vascularize the tumours in the subcutaneous connective tissue and muscle, and that, in contrast, they can easily cross into the lumen of the vessels that surround and vascularize them in the liver and kidney. Thus, this in vivo study indicates that the type of microvascular environment in which certain experimental tumours are transplanted can control their ability to accomplish vascular invasion, the first step of the metastatic process. PMID- 3113065 TI - S-100 protein positive cells in nasopharyngeal carcinoma (NPC): absence of prognostic significance. A clinicopathological and immunohistochemical study of 40 cases. AB - An immunohistochemical study of S-100 protein in 43 nasopharyngeal carcinomas (NPC) of known clinical evolution (33 primary and 10 metastatic) is presented. Sixty per cent of primary site cases as well as all metastatic forms showed S-100 protein positive cells intermingled with tumour cells. These S-100 positive elements were identified as Langerhans cells. No significant differences were found when correlating S-100 protein positivity and histological NPC variants, neither in age nor in sex of patients. Statistical analysis failed to demonstrate any positive correlation between S-100 protein reactivity and clinical survival. PMID- 3113066 TI - Multiple cemental lesions in the jaw bones of a patient with Gardner's syndrome. AB - Unusual multiple lesions of jaws in a middle-aged woman with all classic manifestations of Gardner's syndrome are reported. Clinical examination revealed a diffuse swelling of the mandible and maxilla with bone-like hardness and numerous radiopaque lesions scattered throughout both mandible and maxilla. Impaction of the molar teeth was revealed by roentgenographic examination. Histopathologically, the multiple jaw lesions consisted of trabecular proliferation of hard-tissue which more closely resembled cementum than immature bone or osteoid. It was found to be united with the cementum of tooth-roots through obliteration of the periodontal ligament. The present lesions do not fit into any of the distinct entities of cemental lesions described. PMID- 3113067 TI - Histochemical and proliferative changes preceding the onset of spontaneous gastric adenocarcinoma in Mastomys natalensis. AB - The histochemical and proliferative changes preceding spontaneously developing gastric adenocarcinoma were examined in Mastomys natalensis. The stomachs of 86 inbred animals from the DWZ strain were examined between 1 and 24 months of age. Two thirds of the animals had a small solitary ulcer in the middle of the lesser curvature which was observed by the first month of age. With increasing age, more and more dysplastic glands invading the submucosa were seen around the ulcer and eventually adenocarcinoma was observed after 12 month. Histochemical alterations included increased intracellular peanut lectin and Concanavalin A binding sites in the gastric pits and the development of lectin binding sites and of acid glycoproteins in the surface epithelium. Using 3H thymidine and autoradiography increased labelling and mitotic indices with extension of the progenitor area to the mucosal surface were observed around the ulcer. The coexistence of these histochemical and histokinetic alterations may represent an early sign of malignant potential in the gastric mucosa. PMID- 3113069 TI - Endocrine cells in ectocervical epithelium. An immunohistochemical and ultrastructural analysis. AB - A systematic study of endocrine cells in the ectocervix was carried out using histochemical, immunohistochemical and ultrastructural techniques. Serotonin and calcitonin immunoreactive cells were demonstrated in this site. Serotonin and calcitonin immunoreactivities were coexpressed in the same endocrine cell. These distinctive cells were encountered in two main morphological varieties of ectocervical epithelium. Normal-appearing stratified squamous epithelium contained only very rare serotonin and calcitonin cells. In contrast, endocrine cells were fairly abundant in a specific epithelium termed "transitional-like". This type of epithelium was not only confined to the transformation zone but could also extend onto the portio as far as the vaginal cut margin. In some cases, transitional-like epithelium bore morphological resemblance to urothelium. In other cases, it could be regarded as basal cell hyperplasia or immature squamous metaplasia. Of interest, serotonin and calcitonin cells have been well documented as normal inhabitants of some other non-squamous epithelia, such as urothelium or pseudostratified columnar epithelium. Therefore, it is suggested that certain ectocervical epithelia show some similarities to urothelium, in respect of their morphological appearance and endocrine profile. Further investigations using more objective and specific markers of urothelial cells are needed to assess the exact degree of homology connecting all these types of epithelium. PMID- 3113068 TI - Ultrastructure of tumour invasion and desmoplastic response of bronchogenic squamous cell carcinoma. AB - Using ultrastructural methods we studied the interaction of tumour cells and lung parenchyma in deep areas (i.e., more than about 3 mm from the tumour surface) of 50 bronchogenic squamous cell carcinomas. The tumour periphery, studied previously, had shown organized associations of tumour cells and lung epithelial cells and a surprising lack of invasion of non-epithelial tissue compartments. The deeper areas, where the tumour cells and the lung parenchyma had been in contact for longer periods, consisted of irregular groups of tumour cells and desmoplastic stroma which was very similar to granulation tissue. The deeper areas also contained many intact lung epithelial cells, arranged in compressed and distorted alveolar structures. Where non-neoplastic epithelial cells and tumour cells had direct contact, they formed common junctional complexes and basal laminae. In part of the tumours, the cells were largely devoid of a basal lamina. However, in most instances a continuous basal lamina surrounded every tumour cell group studied, even when these formed irregular strands or seemed to be completely isolated. PMID- 3113070 TI - Expression and glycosylation of the respiratory syncytial virus G protein in Saccharomyces cerevisiae. AB - A cDNA encoding the entire amino acid sequence of the G glycoprotein of respiratory syncytial virus (RSV) was inserted into a yeast-Escherichia coli shuttle vector such that expression of the virus gene was regulated by the yeast GAL1 promoter. Transformation of Saccharomyces cerevisiae with the vector led to the formation of the G protein when cells were grown in the presence of galactose. Under these conditions the RSV G appeared as a 60- to 65-kDa glycosylated protein. Expression of the G cDNA in secretory mutants of S. cerevisiae yielded a protein of 35 kDa in a mutant unable to glycosylate secreted proteins and a 65-kDa polypeptide in a mutant unable to transport proteins beyond the endoplasmic reticulum. The RSV protein formed in the latter mutant was converted to a 60-kDa protein by endoglycosidase H. Our results show that yeast can recognize the internal signal sequence of RSV G protein and add glycosyl groups to the polypeptide in the endoplasmic reticulum. Evidence is presented for both N- and O-linked glycosylation of the virus glycoprotein. PMID- 3113071 TI - Visual development. PMID- 3113072 TI - Cones and opponency. PMID- 3113073 TI - A new technical approach to monkey visual training. AB - To train the monkey for visual task we use the microcomputer and a bicoloured LED. This system is very advantageous in respect of its low cost and the ease of use. PMID- 3113075 TI - [Complications in patients with typhoid and paratyphoid fevers during a period of decline in morbidity]. PMID- 3113074 TI - [Effect of unithiol and lipamide on the cardiovascular function of animals administered cadmium and copper compounds]. PMID- 3113076 TI - [Drug resistance of Mycobacterium tuberculosis]. PMID- 3113077 TI - [Modulation of immune responses with glucocorticosteroids]. PMID- 3113078 TI - [Changes in the factor VIII molecular complex in Hodgkin's disease and non Hodgkin's lymphoma]. AB - Factor VIII molecular complex is included in the proteins of "acute inflammation", being changed not only in the congenital diseases - hemophilia A and Willebrand disease but also in a series of acquired diseases as various inflammatory processes, hypercoagulability, DIC syndrome, neoplasms. The studies carried out on Hodgkin's disease and non-Hodgkin lymphomas reveal that the changes in its separate activities (factor VIIIK and Willebrand antigen) are not unidirectional with the changes of fibrinogen level and cannot serve as an index of the activity of the process. PMID- 3113080 TI - [Waldenstrom's macroglobulinemia presenting as gastrointestinal hemorrhage. Diagnostic difficulties]. PMID- 3113081 TI - [Interstitial stereotactic radiotherapy of brain tumors]. AB - The narrow margin between tumour sensitivity and healthy brain sensitivity to radiation considerably limits conventional radiation therapy (teletherapy). Interstitial radiotherapy (brachytherapy) with iodine-125 permanent implants is effective for local tumour control. So far, interstitial radiotherapy using low activity permanent implants has been carried out in 72 patients with differentiated gliomas (55 cases) and other tumours in functionally critical cortical or deep-seated location. The overall response rate was 64%. In 15 patients, local radiotherapy did not halt clinical deterioration. Brachytherapy with I-125 permanent implants is recommended for slowly proliferating, differentiated, non-resectable tumours in functionally critical areas. It enables the surgeon to achieve radiosurgical tumour removal while carefully avoiding radiation and operative damage to the healthy brain. On the basis of biological, experimental and clinical data, individualized treatment for each patient is desirable. PMID- 3113079 TI - Peptic ulcer disease. Pathophysiology and current medical management. PMID- 3113082 TI - [Reversible opening of the blood-brain barrier in the chemotherapy of malignant gliomas]. AB - The concept of a blood brain or blood tumour barrier blocking the passage of lipid insoluble cytoreductive drugs from blood into brain-tumor, leads to a protocol of intraarterial injection of high dose methotrexate (MTX) during reversible, osmotic blood brain barrier disruption (BBBD). Malignant Gliomas of grades III and IV in 9 patients and one primary CNS-lymphoma in one patient have been treated in 2 to 5 sessions per patient with BBBD plus polychemotherapy (MTX, cyclophosphamide, procarbazine). Median progression free intervals (PFI) which are still in continuation are 12.2 months. Median PFI which had been terminated by tumour recurrence are 7.75 months. PMID- 3113083 TI - [Acute massive gastrointestinal hemorrhage in jejunal diverticulosis]. AB - Two cases which presented with acute massive lower gastrointestinal hemorrhage from jejunal diverticulosis are reported. The various clinical presentations of this rare disease are discussed. The life-threatening complication of massive bleeding is specially outlined. The cases reported in the literature resemble the Dieulafoy ulcer lesion of the stomach. PMID- 3113084 TI - [Skin changes in hemodialysis patients]. AB - 188 patients undergoing long-term hemodialysis and a control group of 371 patients without kidney diseases were examined with regard to changes of the connective tissue of the skin. The following alterations were observed: increased sensibility to low temperatures and Raynaud's syndrome (42%), Dupuytren's contracture (22.4%), sclerosis of the dorsum of the fingers (17.6%). Carpal tunnel syndrome was seen in 24.4% of the cases, significantly correlating with the duration of hemodialysis. PMID- 3113085 TI - [Inhibition of flecainide resorption by activated charcoal]. AB - The effect of orally administered activated charcoal on plasma concentrations of flecainide were studied in eight volunteers (24-38 years of age). A single dose of 200 mg flecainide were given at 3 days: control (day 1); simultaneous application of flecainide and 30 g charcoal (day 2); application of 30 g charcoal 90 min after flecainide (day 3). Plasma concentrations were determined by HPLC after 2, 4 and 6 h. Absorption of flecainide was almost completely prevented, when flecainide and charcoal was ingested immediately. When charcoal was taken 90 min after flecainide, the following flecainide plasma levels were found: after 2 h 231 +/- 62 ng/ml (266 +/- 30 ng/ml control; n.s.), after 4 h 199 +/- 49 ng/ml (232 +/- 27 ng/ml control; P less than 0.05) and after 6 h 155 +/- 42 ng/ml (231 +/- 51 ng/ml control; P less than 0.01). Charcoal seems to be effective in prevention of the absorption of flecainide. A drug interaction may occur if charcoal is given therapeutically, for example in hypercholesterolaemia. Charcoal may be indicated as an additional treatment of flecainide intoxication. PMID- 3113086 TI - [Metabolic changes caused by an extremities tourniquet and its modification by anesthesia procedures]. AB - In 3 groups of 15 patients, respectively, we studied metabolic changes following tourniquet-release after operations of lower extremity. The influence of different anesthetic methods was evaluated by blood-gas-analyses up to 30 minutes after blood-circulation of the lower limb had been reinstalled. Our results demonstrate, that the patients under regional anesthesia with spontaneous respiration (group 1) could preserve their metabolic equilibrium with minor changes within the physiologic range. The intubated patients with controlled respiration (group 2) revealed a marked metabolic acidosis after tourniquet release with insufficient respiratory compensation. Initial values were not reached within 30 minutes. The patients of group 3 (controlled respiration with a 25% increase of the normal minute volume for a period of 5 minutes after release of the tourniquet) had a less severe acidosis than those of group 2. The beneficial influence of spontaneous respiration in compensating metabolic acidosis--even in aged patients--following an ischemic tourniquet has been demonstrated by this investigation. Short-term hyperventilation seems to be the therapeutic tool in patients with controlled respiration to compensate for metabolic acidosis up to a certain extent. PMID- 3113087 TI - [Nurses get 15,000 krona per month]. PMID- 3113088 TI - [Functional hemispheric asymmetry in children with hypersynchronous activity in the EEG. A study with the dichotic listening procedure]. AB - 24 patients of a child psychiatric clinic with focal epileptiform activity located in different brain areas were tested with a dichotic listening procedure to examine functional hemispheric asymmetry. Children with epilepsy were excluded. No differences were found concerning the lateralisation of the examined functions between the clinical groups and a matched-pair non-clinical control group. Clinical groups as well as the control group showed a right-ear-effect (REE), i.e. a superior functioning of the left hemisphere in processing the presented stimuli. However, children with epileptiform discharges in the left hemisphere showed inferior functioning in the dichotic listening test on both ears in contrast to children with bi-hemispheric discharges and the control group. Results were discussed in the theoretical framework of malfunctions of auditory short time memory. PMID- 3113089 TI - [Spontaneous activity and eating behavior of the white-tufted marmoset (Callithrix jacchus)]. PMID- 3113091 TI - [Pseudomonas aeruginosa: pathogenicity, prevention and therapeutic approaches]. AB - Pseudomonas aeruginosa has proved to be a dangerous nosocomial pathogen is growing importance. Its pathogenicity is attributable to its great variety of toxic mechanisms which are capable of attacking all parts of the organism, primarily organs with impaired resistance. Antibiotics had been found to yield little lasting success. Therefore, an attempt was made to apply to 30 patients three-per-cent boric acid to cope with locally delimited Pseudomonas wound infections. Therapy could be completed with good success in less than six days on average. Only germ reduction was achievable on three patients with chronic osteomyelitis. Toxic side-effects were not recordable. PMID- 3113090 TI - [Postoperative low-calorie parenteral feeding]. AB - In parenteral nutrition a distinction can be made between hypocaloric, normocaloric, and hypercaloric forms, depending on the amount of energy supply. Hypocaloric parenteral nutrition has been specifically adjusted to the conditions of postoperative metabolism. Doses between 1.2 g and 1.5 g/kg body weight/d of amino acids are the most important components of peripheral venous nutrition. The economy of amino acid utilisation, primarily by patients not adapted to fasting or to ketone body utilisation, can be improved by a low dosage of 2.5 g of carbohydrates to 1 g of amino acids. Polyols were found to be decisively superior to glucose as energy carriers by taking into much closer consideration the mechanisms of autoregulation in postoperative metabolism and by favouring synthesis of intrahepatic functional proteins to peripheral synthesis. Hypocaloric peripheral venous parenteral nutrition has proved to be effective therapeutic concept by which to bridge the early postoperative phase in elective surgery. PMID- 3113092 TI - [Fiber as a carcinogenic agent]. AB - According to the findings that long, thin, and durable fibres have a high carcinogenic potency after intrapleural and intraperitoneal administration, the elongated shape of a particle represents a carcinogenic agent; this physical phenomenon is a special cause of cancer. It induces a biological process which can lead to cancer by several as yet unknown steps. However, the properties of the material the fibres are made of determine the carcinogenic potency of a fibre in a secondary way although they do not seem to be responsible for the true carcinogenic agent. For example, these properties determine the degree of solubility and flexibility. The persistence of fibres in the tissue is a very important property with regard to their carcinogenic effect because the formation of a tumour takes many years or some decades. It can be assumed that a fibre has to remain by the bronchial or serosa tissue until the induction of tumour cells occurs. If this hypothesis is correct, there could be a "durability threshold value" for fibres whose length and diameter would otherwise indicate a high carcinogenic potency. There are indications that other fibre properties apart from length, diameter and durability are important for tumour induction, however, at present, they cannot be included in a definition of carcinogenic fibres. It is proposed to classify all natural and man-made mineral fibres with an aspect ratio of greater than 5:1 as carcinogenic when they are longer than 3 microns, thinner than 1 micron (or can split into such fine fibres) and when they can persist in the tissue for more than 3 years. PMID- 3113093 TI - Effects of trichloroethylene, tetrachloroethylene and dichloromethane on soil biomass and microbial counts. AB - Trichloroethylene, tetrachloroethylene and dichloromethane in concentrations of 10, 100, and 1000 micrograms per 100 g brown soil (dry weight) had different effects on soil microorganisms. The ATP content of the soil biomass decreased significantly in the first and second week of incubation when 100 micrograms of trichloroethylene and tetrachloroethylene were added to the soil, and it was strongly reduced during the two months of the experiment duration when 1000 micrograms of the individual chlorinated solvents under test was added. Similar inhibitory effects could be observed with soil fungi. Tetrachloroethylene in a dose of 1000 micrograms, however, exerted mainly a stimulative influence as shown by the counts of oligotrophic and copiotrophic aerobic soil bacteria and also by the total counts of anaerobic microorganisms. The same concentrations of trichloroethylene and dichloromethane inhibited both groups of aerobic bacteria in the soil. Actinomycetes were mainly inhibited by addition of 1000 micrograms of the volatile chlorinated solvents but they were not affected by lower concentrations. No significant effects were observed in aerobic spore-forming bacteria, and only slight effects were found also in the spore-forming anaerobic microorganisms of Clostridium sp. In conclusion, with the concentrations of chlorinated solvents which were from 10(3) to 10(6) higher than the actual 'in situ' soil contamination, some negative effects on soil microorganisms could be observed. However, one or two month after the soil was contaminated, the microbial counts increased again. PMID- 3113094 TI - Enumeration of salmonellas by most probable number method from sewage and sewage polluted natural waters, comparing the use of preenrichment versus direct enrichment in NR10 at different temperatures. AB - Crude sewage and sewage-contaminated natural waters were analysed for the presence of Salmonella by Most Probable Number Procedures, Direct enrichment in NR10 at 37 degrees C and 43 degrees C was compared with preenrichment in buffered peptone water at these two temperatures, followed by selective enrichment in NR10 at 37 degrees C and 43 degrees C. The growth of competing bacteria on Hektoen agar plates was also recorded and quantified. Direct enrichment in NR10 gave higher numbers in both types of waters. The temperature of 37 degrees C was more favourable for the less heavily contaminated waters, whereas 43 degrees C was more efficient for crude sewage. The growth of competing bacteria was restricted at 43 degrees C and enhanced at 37 degrees C. With direct enrichment in NR10/43 degrees C, pure Salmonella cultures can be obtained after 48 h incubation. PMID- 3113095 TI - Stability of two forms of Rappaport-Vassiliadis enrichment medium. AB - It has been shown previously (18) that the sensitivity of Rappaport-Vassiliadis medium (RV medium) prepared with tryptone Difco (RV-tryptone) in isolating salmonellae and its specificity in inhibiting competing organisms remains unchanged when the medium is held in a refrigerator for 6 to 7 months. In the present study it was found that the RV-tryptone medium held in the refrigerator for 13 to 15 months looses its specificity to a marked extent. Therefore it is prudent not to use RV-tryptone after storage of 7 months. On the other hand, it was observed that RV medium made with soya peptone (Oxoid L 44) (RV-soya) retains its sensitivity and specificity, and is therefore usable, when held in the refrigerator for 7 to 9 months and even when held at room temperature for 13 to 15 months. PMID- 3113096 TI - Occurrence of Yersinia spp. in raw beef, pork and chicken. AB - One hundred and twenty raw ground beef, pork and chicken samples from ten local grocery stores during a one year period were assayed for the presence of Yersinia spp., using direct and postenrichment KOH treatment. Seven thousand and fifty five different isolates were recovered from 119 (99%) samples of beef and pork and 118 (98%) samples of chicken, including 27 Yersinia enterocolitica serotype 03 biotype 3B phage type 2 (4 pork samples), 4 Y. enterocolitica serotype 03 biotype 4 phage type 8 (3 pork samples), 4,066 Y. enterocolitica biotype 1, 2,194 Yersinia intermedia, 509 Yersinia frederiksenii, and 251 Yersinia kristensenii. Y. enterocolitica serotype 03 was isolated from 6 pork samples, including simultaneously isolation of both biotypes 3B and 4 from one sample. There was the negative correlation between the incidence of isolation of serotype 03 and the environmental temperature, but other environmental Yersinia spp. were frequently isolated through the year. Y. enterocolitica serotype 03 isolates were counted by alkali direct treatment at less than 10(3) cells per g of pork samples, and environmental Yersinia spp. at less than 10(5) cells per g of beef, pork and chicken samples. This may be the first evidence that some pork is contaminated with at least 10(3) Y. enterocolitica serotype 03 cells per g. PMID- 3113097 TI - Collaborative study on the precision of the enumeration of Staphylococcus aureus in food. AB - In order to compare the precision of the enumeration of Staphylococcus aureus in food with egg yolk tellurite glycine pyruvate agar (ETGP-agar) and with rabbit plasma fibrinogen agar (RPF-agar), a collaborative study was carried out in which 23 laboratories participated. In this study each laboratory examined an identical series of 10 samples of ice cream, artificially contaminated with S. aureus and other Gram-positive cocci at roughly 10(4) per ml. The variations between the participating laboratories were smaller with RPF-agar than with ETGP-agar. The average values of the standard deviations were 0.10 and 0.13 log-units respectively. Laboratory specific errors were limited to 0.15 log-units with both media. For RPF-agar repeatability (r) was 0.26 (in log-units) and reproducibility (R) was 0.31 and for ETGP-agar r was 0.37 and R was 0.39. It is concluded that variations in S. aureus counts are limited and reproducibility is improved by using RPF-agar. PMID- 3113098 TI - [The induction of sister chromatid exchange by diethylstilbestrol and mitomycin C in lymphocytes of mothers and their newborn infants]. AB - Lymphocytes of mothers and their newborn infants were treated with varying concentrations of diethylstilbestrol (10(-6) M, 10(-5) M and 10(-4) M) and mitomycin C (0.003, 0.009 and 0.03 microgram/ml), and the incidence of sister chromatid exchanges (SCE) was determined. The results showed that the spontaneous SCE rate in the newborns is less than that of their mothers. A dose-related increase in SCEs was observed in cells exposed to the alkylating chemical mitomycin C, while increases in SCEs were not noted in cultures exposed to diethylstilbestrol. No different susceptibilities of lymphocytes from mothers and newborns to the chemical induction were observed. PMID- 3113099 TI - [Tuberculin conversion rate in long-term employees of a university hospital during the period from 1975 to 1985]. AB - During the period of 1975 until 1985 the tuberculin conversion rate has been determined for 142 persons who have been employed more than 4 years in an university hospital. The current records of the occupational medical investigation-department in which 5,700 case sheets have been stored at the beginning have been available for the selection of these subjects. After a latent period of 2.5 years 9.2% of the employees converted. The highest conversion rate of 16.7% was settled amongst those staff occupied in a lower level, e.g. craftsmen, charwomen, laundress, kitchenhelp, servants and so on. The second in high responder-quote was found in the nursing personal with 9.9% followed by the laboratory staff with 8.7%. Within the office workers no tuberculin positive reagent has been observed. Whilst the interpretation of the tuberculin conversion rate there must be taken into consideration beside the occupational dependent sensibilization against tuberculosis bacteria the non occupational contamination sources, too (like smear- and droplet infection due to usual social contacts or household-contacts resp.). PMID- 3113100 TI - [Dependence of microbiologic test results of formaldehyde gas sterilization methods on the nature of the test material]. AB - The efficiency of a formaldehyde gas sterilization procedure was evaluated with the aid of test pieces consisting of various materials. Both rigid and flexible tubes served as test pieces. The tubes were 75 cm long with an inner diameter of 1 mm and were sealed at one end. The bioindicators were placed inside the tubes close to the sealed end. Dried spores of Bacillus stearothermophilus adhering to linen threads served as test organisms. The test results varied according to the material of the test pieces and the thickness of their walls (see Table 1). In flexible tubes made of silicon rubber, all bioindicators became sterile, in tubes of stainless steel, all bioindicators exhibited test organisms that had survived. The findings for materials such as polyvinyl chloride, polyethylene, polyamide and polytetrafluorethylene ranged between these two extremes; the frequencies of bioindicators containing viable germs were 10, 55, 68 and 85%, respectively. Rigid and flexible tubes which had been sealed at both ends served to demonstrate that silicon rubber and polyvinyl chloride were highly permeable for formaldehyde and water vapour. Also the other plastic materials tested were permeable for formaldehyde and water vapour but longer exposure periods were needed to create conditions in the interior of the tubes that would result in a killing of the test organisms (see Fig 2). In this respect, polyamide exhibited a peculiar behaviour. The number of viable spores remained at the initial level for a long period before a decline took place. From the results of testing, it is concluded that test pieces must conform to the objects to be sterilized not only in their dimensions (length, inner diameter) but also in the characteristics of their material. The walls of the test pieces should not have a higher permeability for formaldehyde and water vapour than the material to be sterilized. The highest demands on the efficiency of formaldehyde gas sterilization procedures are those created by mental tubes and thick-walled flexible polytetrafluorethylene. Instruments and devices to be sterilized by a formaldehyde gas procedure should be preferentially made of materials which are sufficiently permeable for formaldehyde and water vapour as e.g. silicon rubber. Such gas-permeable components may considerably facilitate the sterilization of cavities which have a small lumen and are difficult to reach. PMID- 3113101 TI - [Determination of formaldehyde concentration in a low-pressure sterilizer]. AB - Two methods are described in determining the concentration of Formaldehyde in the sterilisation chamber of a regular commercial sterilizer. The measurement and flow of the concentration is ascertained during a routine sterilization procedure. With regard to the biological efficiency test of the examined apparatus the stability of the active Formaldehyde concentration is controlled. The difficulty in the determination of the Formaldehyde in such sterilizers is due to the fact that samples must be taken at a reduced pressure of 200 mbar. We have developed two different sampling methods. By employing the first continual collection method Formaldehyde gas is drawn out of the sterilization chamber with a high vacuum pump and conveyed with hydrogen into a nickel catalysator, whereby Methane is formed. The determination of Methane is carried out with a flame ionisation detector (F.I.D.). The results of the F.I.D. method are between 10.1 10.8 mg Formaldehyde per litre of gas. It is possible to detect a slight, even reduction in the Formaldehyde concentration throughout a period of 90 min. With the second discontinual method of determination vacuum tubes are employed which are furnished with external magnetic valves for control. By opening the magnetic valves briefly during the pre-vacuum therewith causing loss of pressure, Formaldehyde gas can be collected in the vacuum tubes throughout the sterilization procedure. The determination of the samples extracted by the discontinual method is carried out spectrophotometrically using the p-Rosanilin method after Miksch et al. The second method of determination shows values of 9.0 9.8 mg/l (Sx = 0.8 mg/l). These results lie somewhat lower than those of the F.I.D. determination. The flow of the concentration during 90 min. shows an average reduction of 7.4% and matches exactly the curve which was obtained by the F.I.D. method. By measuring the Formaldehyde concentrations which goods are subjected to in normal sterilization procedure it is possible to examine the efficacy of Formaldehyde sterilizers under regular conditions. Only by quotation of the Formaldehyde concentration present is it possible to reproduce details on sterilization times of treated articles. PMID- 3113102 TI - [The mechanism of action of aerosol disinfection]. AB - It is drawn up a list of physical laws describing the behavior of an aerosol system. First the influence of sedimentation, diffusion, coagulation and impaction is described. In the second part the evaporation and the condensation from droplets in relation to the vapor tension of disinfectants is regarded. Finally the circumstances under which the vaporized disinfectants will reach the microorganisms by diffusion are described. It is demonstrated, that the terminus technicus "aerosol disinfection" should be restricted to systems, that operate with drop diameters less than or equal to 10 microns. PMID- 3113103 TI - Influence of the growth characteristics of Candida albicans on disinfectant testing. AB - In order to standardize antifungal disinfectant testing using Candida albicans as a test organism, the morphology of four type strains of C. albicans DSM 1836, ATCC 10231, CNCM 1180-79 and CBS 562, grown on sixteen different media was determined. The incubation was carried out at 28 degrees C and 37 degrees C. The yeast phase was obtained predominantly on TSA medium with all strains. Mixed phases, i. e. true mycelium and yeast cells, were easily obtained in TSB in shaking flasks for three type strains but not for CBS 562. True mycelium was formed on corn meal media (CMA) for all strains, but the growth was very poor. The morphology of the growth was determined more by the type of strain than by the nutritive medium. Therefore C. albicans ATCC 10231 grown on either TSA or CMA was used as a test organism. Its resistance was determined towards four disinfectant standards: benzalkonium chloride, mercuric chloride, phenol and o phenylphenol. No difference in sensitivity was found for the former disinfectant, but yeast cells grown on TSA were more resistant than C. albicans cultures on CMA in case of mercuric chloride, phenol and o-phenylphenol. PMID- 3113104 TI - [The enzymatic degradation of formaldehyde by isolates of Pseudomonas aeruginosa]. AB - The capacity of 12 Ps. aeruginosa-strains to enzymatically degrade Formaldehyde was tested. These strains, derived from environmental and patient samples, were previously passaged 25 times in increasing formaldehyde-concentrations, in a micromodification of the bacteriostasis test. The formaldehyde-degradation was detected photometrically with the sulfite-pararosaniline-method. Furthermore, in 4 of the 12 strains the activity of a formaldehyde dehydrogenase assumed to be the degrading agent was determined. The tested strains exhibited a markedly differing resistance to formaldehyde, some environmental isolates growing even at concentrations in the range of commonly used disinfectant solutions. The exponential growth phase of the inoculum and the reduction of formaldehyde content coincided. The strains with the highest formaldehyde-resistance showed a formaldehyde-dehydrogenase activity higher by approximately a factor 100 compared with the rather sensitive ATCC-strain. This dehydrogenase activity, in addition to possible extra- and intracellular penetration barriers, could be a causal factor for an increased formaldehyde-resistance. PMID- 3113105 TI - [Thirty years of disinfection 1955-1985]. AB - The article deals with disinfectants and disinfection during 1955-1985 and analyses the disinfectant lists no. 1-6 made up by the German Society for Hygiene and Microbiology. It is shown that changes in test methods may influence the composition of disinfectants. During the time taken in consideration a change from phenols/phenol derivatives as main active material in disinfectants to aldehydes took place. Main active materials in hand disinfectants are the alcohols ethanol, iso-propanol and n-propanol. Since 1974 (list no. 4) the number of products based on PVP-iodine for hand disinfectants increases. Strikingly quaternary ammonium compounds in detergent disinfectants increase as well as sole active material or in combination with aldehydes. This depends on the fact, that their acceptance is well because they are less smelling. On the other hand in combination with aldehydes they make it possible to reduce the amount of bad smelling aldehydes. PMID- 3113106 TI - [Maturational changes in the bovine ECG. II. Ventricular recovery]. PMID- 3113107 TI - Postpartal ovarian function in Holstein and crossbred cows on large scale farms in Hungary. PMID- 3113108 TI - Effects of oestradiol-17 beta and progesterone administration during day and night in white Leghorn hens on catecholamine levels in different areas of brain. PMID- 3113109 TI - [Long term studies of the influence of the energy supply during pregnancy on body weight changes and reproductive performance in the sow]. PMID- 3113110 TI - Distribution of load between the lateral and medial hoof of the bovine hind limb. PMID- 3113111 TI - Presence of serotonin in the hen reproductive tract. PMID- 3113112 TI - Effects of verapamil and nifedipine on smooth muscle of equine intrapulmonary arteries. PMID- 3113113 TI - Relaxation of ruminal smooth muscle by vasoactive intestinal polypeptide (VIP). PMID- 3113114 TI - [Plasma levels of estradiol-17beta and estrone in cows before parturition, with special reference to the concentration in the subcutaneous abdominal vein and the uterine vein]. PMID- 3113115 TI - [Meiosis in fowl and laboratory mammals in late prophase and metaphase stages]. PMID- 3113116 TI - [Qualitative and quantitative distribution of 7 enzymes in organs of the rainbow trout (Salmo gairdneri R.) and the carp (Cyprinus carpio)]. PMID- 3113117 TI - Seasonal variation of the ovarian function in unmated sows revealed by the measurement of progesterone and 17 beta-oestradiol in peripheral bloodplasma. PMID- 3113118 TI - Bioavailability to chicks of selenium in wheat and fish meal. PMID- 3113119 TI - Kinetics of L-lactate in pigs. I. Studies in resting pigs using different marker methods. PMID- 3113120 TI - Kinetics of L-lactate in pigs. II. Studies in stress resistant and stress susceptible pigs under different metabolic conditions. PMID- 3113121 TI - Acid alpha naphthyl acetate esterase activity in peripheral blood lymphocytes and monocytes of chickens. PMID- 3113122 TI - [Organ and plasma enzyme patterns of the rainbow trout (Salmo gairdneri)]. PMID- 3113123 TI - Epidural spinal metastasis of canine transmissible venereal sarcoma. PMID- 3113124 TI - [Sclerosing mesothelioma in the dog]. PMID- 3113125 TI - Alterations in reproductive tissue concentrations of oxytocin and prostaglandins during early pregnancy in the goat. PMID- 3113126 TI - Canine and feline oral-pharyngeal tumours. PMID- 3113127 TI - Origin of the low pH values along the proximal duodenum in sheep. PMID- 3113128 TI - Skin collagen conformation in canine spondylarthrosis. PMID- 3113129 TI - Bovine granulocytopathy syndrome: neutrophil dysfunction in Holstein Friesian calves. PMID- 3113130 TI - Histological findings in skeletal muscles of pigs with different stress susceptibility. PMID- 3113131 TI - Cardiovascular, biochemical and radiographic evaluation of pulmonary lobectomy by rib resection and mid sternal approach in calves under halothane anaesthesia and intermittent positive pressure ventilation. PMID- 3113132 TI - Inhibition of chloride absorption from the sheep rumen by nitrate. PMID- 3113133 TI - [Demonstration of antibodies against Chlamydia psittaci and Coxiella burnetii in dogs and cats: comparison of the enzyme immunoassay, immunoperoxidase technic, complement fixation test and agar gel precipitation test]. PMID- 3113135 TI - [Adhesion of Corynebacterium diphtheriae]. AB - The conditions for the direct hemagglutination test performed to determine the degree of adhesion of C. diphtheriae were defined. For this test sheep red blood cells, trypsin-treated ex tempore, were used. Only newly isolated cultures, subcultured for not more than 2-5 times and stored for not more than 2-7 days or freeze-dried, were employed. The culture to be tested was grown in nutrient agar with 10% of normal horse serum. The test was made in microtitrator round-bottom wells. The mixture of different dilutions of the culture was incubated for 2 hours at 37 degrees C, then left overnight at 4 degrees C. All 147 newly isolated or freeze-dried C. diphtheriae strains under test had different degrees of adhesion. Their adhesive activity was unrelated to their biovar. Toxigenic strains were significantly more active in hemagglutination (53.5 +/- 3.0%) than nontoxigenic ones (23.5 +/- 3.9%). The strains isolated from the nose, irrespective of their biological properties, were more active than those isolated from the pharynx. PMID- 3113134 TI - [The problem of a combination of tuberculosis and alcoholism]. PMID- 3113136 TI - [Dependence of membrane protein turnover in Mycoplasma cells on the age of the culture]. AB - To understand the molecular mechanisms of damages appearing in biological membranes in the process of cellular aging, changes in the rate of catabolic processes in Mycoplasma cells have been studied. This study has revealed that the aging of Acholeplasma laidlawii culture is accompanied by a decrease in the activity of such catabolic enzymes as DNA-ase, RNA-ase, cathepsin D and beta glucosidase. A considerable increase in the duration of the half-life of membrane proteins has been registered, which is indicative of a decrease in their turnover rate. The electrophoretic separation of membrane proteins has revealed essential changes in their properties. Such decline in the functional activity of the plasma membrane of Mycoplasma cells at the stationary phase is probably due to the inactivation of membrane enzymes and to the decreased rate of their turnover. PMID- 3113137 TI - [Meningococcal serogroup B infection]. AB - The results obtained in the examination of patients with meningococcal infection during the period of 1980-1985 are analyzed. The increasing role of serogroup B meningococci in the etiology of the generalized forms of infection, especially in children aged under 3 years and in adults over 50 years, is shown. As noted in this investigation, the disease induced by group B meningococci runs a more severe course. Morbidity caused by this serogroup of meningococci does not result in epidemics in our country. The distribution of patients among different age groups and specific features of the clinical course of the disease in connection with the serogroup of the causative agent make it possible to regard the risk groups as groups with decreased reactivity, which raises doubts concerning the possibility of forming effective postvaccinal immunity against group B meningococci in such persons. PMID- 3113138 TI - [Safety, reactogenicity and immunological activity of a group A meningococcal polysaccharide vaccine for children 1-4 years old]. AB - In the controlled trial carried out among children aged 1-4 years, the safety, reactogenicity and immunological potency of group A meningococcal polysaccharide vaccine produced at the Gabrichevskii Research Institute of Epidemiology and Microbiology (Moscow) were studied. The vaccine under test was introduced in two doses containing 15 and 25 micrograms of meningococcal polysaccharide. Both doses were shown to be safe, faintly reactogenic and immunologically potent. Systemic reactions were manifested by a transient rise in temperature to subfebrile levels in 19% and to 37.8-38.2 degrees C in 4.7% of the vaccinees. The temperature dropped to the normal level by the end of the first day following vaccination. At the site of injection skin hyperemia up to 2-3 cm in diameter was registered in 74% and up to 5-6 cm in diameter, in 6% of the vaccinees. Hyperemia disappeared on day 2 after vaccination. The production of antibodies to group A meningococcal polysaccharide occurred in response to both doses under test, and the elevated antibody level (in comparison to the initial one) was retained perceptibly longer in response to a dose of 25 micrograms; this dose, considering its low reactogenicity, was chosen as the optimal dose for children of the above age group. PMID- 3113139 TI - [Late sequelae of brain injuries]. AB - Clinico-neurologic and electrophysiologic examination of 338 patients in the long term period of brain trauma has permitted the identification of 5 principal syndromes: cerebro-focal, hypothalamus--brain stem, hypertensive-hydrocephalic, asthenoneurotic and epileptic. The characteristics of the clinical course of the syndromes with regard to the nature, localization and duration of isolated and combined craniocerebral injury are outlined. PMID- 3113140 TI - [Use of L-DOPA in the complex treatment of severe craniocerebral injuries]. AB - The article is based on an analysis of the results of clinicobiochemical study of 15 patients with severe craniocerebral trauma (SCCT) whose intensive multiple modality treatment included the use of L-DOPA. All the patients presented with direct traumatic lesions of the subcortical structures attended by diminished excretion of dopamine and DOPA. A favourable clinical effect was related to the use of DOPA which indicates that it is advisable that the drug be included into the combined therapy of severe injury to the brain attended by dysfunction of the subcortical formations. PMID- 3113141 TI - [Molecular mechanisms of nervous system development during the intrauterine and postnatal periods (review of the literature)]. PMID- 3113142 TI - Methodological problems in evolutionary biology. VIII. Biology and culture. AB - Biology cannot accommodate all aspects of culture. Aspects of culture that a biological approach can take into account can be covered by the biological categories of "phenotype" and "environment". There is no need to treat culture as a separate category. Attempts to elaborate biological explanations of "cultural variation" will meet with success only if biologists expand theories of development, and integrate them in evolutionary biology. The alternative- elaborating the idea of so-called "cultural inheritance"--makes little sense from a biological point of view. PMID- 3113143 TI - A general framework for understanding the effects of variability and interruptions on foraging behaviour. AB - A general framework for analysing the effects of variability and the effects of interruptions on foraging is presented. The animal is characterised by its level of energetic reserves, x. We consider behaviour over a period of time [O,T]. A terminal reward function R(x) determines the expected future reproductive success of an animal with reserves x at time T. For any state x at a time in the period, we give the animal a choice between various options and then constrain it to follow a background strategy. The best option is the one that maximizes expected future reproductive success. Using this framework, we show that sensitivity to variability in amount of energy gained is logically distinct from sensitivity to variability in the time at which food is obtained. We also show that incorporating interruptions results in both a preference for variability in time and a preference for a reward followed by a delay as opposed to the same delay before the reward. PMID- 3113145 TI - Presence of aflatoxin B1 in human liver referred to as Reye's syndrome in Venezuela. PMID- 3113144 TI - Parenteral nutrition via the portal vein in rats. AB - A rat model was designed for continuous infusion of complete parenteral nutrition (CPN) via the hepatic portal vein. The purpose was to evaluate possible side effects compared with conventional continuous systemic CPN via the superior caval vein, which bypasses the liver. Observed side effects of transcaval CPN (increase of liver weight and of intraabdominal fatty tissue, granulomatous infiltration of liver and spleen, vascular changes and fat droplets in the lungs) were less when the nutritional substances were infused into the portal vein. PMID- 3113146 TI - Hormonal profile in pubertal females with chronic renal failure: before and under haemodialysis and after renal transplantation. AB - The effects of chronic renal failure on the hypothalamic-pituitary-ovarian axis in 25 girls, aged 9.1 to 20.9 years (mean 13.8) were studied. Twelve patients on conservative treatment (group A) had serum creatinine values between 176.8 and 1502.8 mumol/l; 9 patients were on haemodialysis (group B); and 12 patients had received a renal transplant (group C). Tanner stage of breast development was delayed relative to chronological age in 5 out of 18 patients. Serum oestradiol was normal or low when related to pubertal stages in all groups. Serum LH was elevated in group A and B patients, but normal in group C patients. Serum FSH was elevated in 6 out of the 21 patients in group A plus B, and in 2 out of the 12 patients in group C. Serum PRL was elevated in 12/12, 6/8, and 4/11 patients in group A, B, and C respectively. After GnRH administration to 4 patients in group A, 3 showed delayed or absent gonadotropin response; all 4 patients studied in group C showed normal gonadotropin response. The data indicate a decreased E2 secretion, abnormal gonadotropin and PRL levels and a blunted gonadotropin response to GnRH in girls with chronic renal failure. These results seem to indicate an alteration of the hypothalamic-pituitary unit that can be reversed after successful renal transplantation. PMID- 3113147 TI - Naloxone administration does not affect gonadotropin secretion in patients with Klinefelter's syndrome. AB - Plasma LH and FSH were measured every 20 min in a group of patients with Klinefelter's syndrome before and after placebo or naloxone administration (8 mg iv as a bolus followed by an infusion of 4 mg/h for 4 h) both in baseline conditions (N = 6) and during treatment with testosterone enanthate (200 mg im every two weeks; N = 4). The mean LH areas measured during saline infusion in baseline conditions (7888 +/- 758 IU/l per min mean +/- SEM) and during testosterone treatment (5042 +/- 2039 IU/l per min) were not significantly different from those measured during naloxone infusion (baseline 8317 +/- 818 IU/l per min; during testosterone treatment 5395 +/- 2007 IU/l per min). Similar results were obtained for FSH. These data suggest that in patients with Klinefelter's syndrome, the opioidergic inhibition of gonadotropin release is lacking and is not restored by testosterone replacement therapy. PMID- 3113149 TI - Testicular growth and hormonal parameters in the male Snell dwarf mouse. AB - Dwarf mice show delayed testicular growth and their adult testis weights are half the normal value. The aims of the present work were firstly, to compare the developmental profiles of plasma gonadotropins and of testicular cell multiplication and differentiation in dwarf vs normal mice and secondly, to determine the effect of hMG supplementation on dwarf mice. In the dwarf mice no pubertal rise in plasma FSH was observed, and the adult values remained very low when compared with those of normal mice; plasma LH decreased after 40 days of age and remained equal to half the normal values. In adults, testicular testosterone content was greatly increased in dwarf mice compared with normal mice, whereas plasma testosterone and accessory gland weights were reduced. At 24 days of age, the total numbers per testis of Leydig and Sertoli cells were reduced in dwarf vs normal mice, whereas in adult mice their differentiation, but not their total numbers, was reduced. This resulted in lower daily production of leptotene primary spermatocytes and of round spermatids in dwarf than in normal mice. hMG supplementation promoted Leydig and Sertoli cell multiplication, but did not produce full differentiation, resulting in increased daily production of round spermatids. In conclusion, in adult dwarf mice a deficiency in plasma gonadotropins prevents full differentiation of Leydig and Sertoli cells without affecting the number of these cells. PMID- 3113148 TI - Endocrine investigations in two cases of feminizing Leydig cell tumour. AB - Two patients, aged 32 and 35 years, presented with gynaecomastia and a unilateral testicular tumour which proved to be a Leydig cell tumour. Pre-operative samples taken at 08.00 h on different days showed marked elevation of plasma oestradiol in the first patient, and very slight irregular oestradiol elevation in the second, plasma oestrone within the normal range in both patients, reduced plasma testosterone in the first patient and reduced or normal testosterone in the second, and low or low-normal serum LH and FSH in both patients. One of the patients received an oral dose of 100 mg of clomiphene citrate for 3 consecutive days which induced a rise in LH and FSH and a decrease in the 17 hydroxyprogesterone/androstenedione ratio. These data suggest the inhibiting effect of endogenous hyperoestrogenism on testicular steroidogenesis owing to both the reduction of gonadotropin secretion and a direct local negative effect on C 17,20-lyase. After human chorionic gonadotropin stimulation, oestradiol response was increased and abnormally prolonged, a finding which may be helpful when diagnosing a feminizing Leydig cell tumour; testosterone reached normal values. After removal of the tumoural testis, gynaecomastia regressed within a few days, gonadotropins increased, oestrogens dropped, testosterone and 5 alpha dihydrotestosterone normalized in one patient but remained low in the other at day 30. The Leydig cells outside the tumour appeared morphologically normal, but the count gave evidence of juxtatumoural Leydig cell hyperplasia in areas where the tumour was well encapsulated while showing a significant reduction at a distance from the tumour and in the contralateral testis by comparison with control testes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113150 TI - TSH and biogenic amine signals in the regulation of thyroid function: independent regulation by protein kinase C and G proteins. PMID- 3113151 TI - Influence of exogenous interleukin-2 on the proliferation of lymphocytes from normal donors and from patients after autologous bone marrow transplantation. AB - The influence of two interleukin-2 (IL-2) preparations on the proliferative response of normal lymphocytes to phytohemagglutinin (PHA) was examined. A recombinant IL-2 (rIL-2) and an IL-2 containing conditioned medium (LyIL-2) markedly enhanced 3H-thymidine incorporations at low PHA concentrations, whereas at optimal mitogen concentrations, this effect was marginal. In lymphocyte cultures of 3 patients after autologous bone marrow transplantation (ABMT), exogenous IL-2 augmented PHA-induced stimulations. Moreover, a dose-dependent increase of the 3H-thymidine uptake was observed in unstimulated cultures of all normal donors and patients. Combined autoradiography and surface marker analysis allowed to identify cells spontaneously proliferating in the presence of exogenous IL-2. Comparison of phenotypes of these cells revealed pronounced differences between a normal donor and a patient after ABMT. PMID- 3113152 TI - Translocation of oncogene c-sis from chromosome 22 to chromosome 17 in a human myelogenous leukemia cell line. AB - By combining somatic cell genetics, in situ hybridization and Southern hybridization, we found that the c-sis oncogene in the human myelogenous leukemia cell line ML3 is translocated from the long arm (q11----qter) of chromosome 22 to the long arm (mid-portion or q21 region) of chromosome 17. This translocation does not result in rearrangement of the c-sis oncogene. PMID- 3113153 TI - Proliferative characteristics of acute nonlymphocytic leukemia in vivo. AB - The proliferative characteristics of myeloid leukemias were defined in vivo following intravenous bromodeoxyuridine (BrdU). Fifteen patients received a 2 hour infusion of BrdU. A monoclonal anti-BrdU antibody was used to detect the in vivo incorporation of BrdU by S-phase cells. The percentage of S-phase cells obtained from the biopsies (mean 17.3%) was significantly higher (p = 0.00001) than the percentage determined from the aspirates (7.8%). It is concluded that the true estimate of S-phase cells can only be obtained from biopsies following in vivo labeling of cells synthesizing DNA. The persistence of BrdU-labeled cells in follow-up studies can be used to recognize 'residual leukemia', and the subsequent fate of these cells can be defined in vivo. PMID- 3113154 TI - Bone marrow plasmocytosis in acute leukemia. AB - A quantitative evaluation of IgA, IgD, IgG and IgM plasmocytes in sequential bone marrow aspirates of patients with acute leukemia using the peroxidase antiperoxidase method was undertaken. Plasmocytosis resembled that of normal controls or was slightly subnormal on admission. When remission was obtained, bone marrow plasmocytosis was similar to normal controls, irrespective of the type of acute leukemia and the cytostatic treatment. Occurrence of infection strongly augmented the number of plasmocytes, with an initial increase in IgM and later in IgG plasmocytes. This suggests that the immune response is preserved in patients with acute leukemia. PMID- 3113155 TI - Effects of washing and gel filtration on the ultrastructure of human platelets. AB - The ultrastructure of washed and gel-filtered platelets has been examined by scanning- and transmission-electron microscopy. Three different washing procedures previously established for functional studies have been employed. Each washing method resulted in typical morphologic alterations of the platelets. Gel filtration of platelet-rich plasma appeared less harmful than washing. Specimens fixed immediately after elution contained numerous platelets with typical shape changes which were restored almost completely after incubation at 37 degrees C. Our study emphasizes the need for cautious interpretation of results obtained with separated platelets and mandates morphologic controls for such experiments. PMID- 3113156 TI - Coagulation changes in sickle cell disease in early childhood. AB - Measurements of the coagulation system were carried out in children with sickle cell disease (SCD) in both steady state and on the 1st day of painful crisis and were compared to age- and sex-matched healthy controls. No significant differences were found in prothrombin time, partial thromboplastin time, thrombin time, reptilase time, plasma fibrinogen, antithrombin III, factor VIII:C, ristocetin-cofactor (Ri-Cof) and platelet aggregation responses to ADP, collagen and adrenaline. Abnormal aggregation responses to ristocetin were noted in all patients with SCD when compared to controls. Daily measurements during the first 4 days of painful crisis showed significant elevation of fibrinogen and Ri-Cof and enhancement of aggregation to ADP and adrenaline by the 3rd day of crisis. It was concluded that the changes noted, rather than being primarily responsible for the onset of crisis, can only be secondary changes arising from the aetiological factors of crisis, i.e. stasis and acute-phase proteins. PMID- 3113157 TI - Danazol therapy in acquired idiopathic sideroblastic anemia. AB - Danazol, a synthetic androgen, was used in the treatment of 6 patients with acquired idiopathic sideroblastic anemia. No patient had a response to therapy as determined by an increase in either the hemoglobin or platelet count. PMID- 3113158 TI - T cell gamma chain gene rearrangement without T cell receptor beta chain gene rearrangement in two cases of non-Hodgkin's lymphoma. AB - We report two patients with non-Hodgkin's lymphoma whose neoplastic cells had rearranged T cell gamma chain (T gamma) genes, and had the germ line DNA of T cell receptor beta chain (T beta) and immunoglobulin genes. Surface marker analysis of the neoplastic cells revealed that leukemic cells from one patient were derived from common thymocytes, while in the other patient the clonality and cell lineage could not be identified, probably due to the low percentage of neoplastic cells in the specimen. No phenotypic changes were observed after cultivation with phorbol myristate acetate, except for induction of Tac antigens on cells of one patient. Leukemic cells with only the T gamma gene rearrangement are thought to be precursor T cells that differentiate into mature T cells following T beta gene rearrangement. This suggests that such T cells with only the T gamma gene rearrangement exist among common thymocytes. PMID- 3113159 TI - Abnormalities of T cell subsets in a patient with cyclic neutropenia. AB - The case of a patient suffering from recurrent episodes of fever over a period of 24 months is presented. A diagnosis of cyclic neutropenia was made and a persistent inversion of the T helper/suppressor ratio was demonstrated in the peripheral blood. PMID- 3113160 TI - High-voltage irradiation and hydroxyurea for pulmonary leukostasis in acute myelomonocytic leukemia. AB - A 29-year-old man with acute myelomonocytic leukemia had an initial leukocyte count of 192 X 10(9) cells/l and 84% blasts. During the initial treatment with hydroxyurea, 1 g/m2 orally tid, he developed pulmonary leukostasis which responded rapidly to whole-lung radiation with 1.5 Gy in one fraction. Pulmonary leukostasis in hyperleukocytotic AML is an oncologic emergency demanding rapid intervention. The combined treatment with chemotherapy and radiation appears useful. PMID- 3113161 TI - Recurrent life-threatening epistaxis in a child with Bernard-Soulier syndrome controlled by bilateral ligation of external carotids and ethmoidal arteries. AB - Bilateral ligation of external carotids and ethmoidal arteries proved successful in controlling severe recurring epistaxis in a 13-year-old patient with Bernard Soulier syndrome. In this child, epistaxis was the major bleeding symptom. Despite massive substitutive therapy, the patient suffered several life threatening episodes of hypovolaemic shock. Although epistaxis is not reported as a cause of death in patients with haemostasis defect, our case might suggest that in selected cases with inherited platelet defect and intractable epistaxis so severe as to make normal or near-normal life impossible, surgical treatment could be considered. PMID- 3113162 TI - Masked phenytoin-induced megaloblastic anemia in beta-thalassemia minor. AB - We report the occurrence of megaloblastic hematopoiesis with peripheral microcytosis in a beta-thalassemic heterozygote who developed profound anemia secondary to folate deficiency. The folate deficiency was precipitated by prolonged therapy with diphenylhydantoin. In thalassemic heterozygotes who develop anemia, the possibility of a megaloblastic pathogenesis should be pursued even when the RBC indices maintain their microcytic-hypochromic expression. PMID- 3113163 TI - Transient acquired blood group B antigen associated with diverticular bowel disease. AB - Transient acquired B red cell antigen was found in a patient with inflammatory bowel disease. Removal of the affected portion of the bowel was associated with disappearance of the B antigen. This phenomenon has usually been recorded in association with neoplasms of the bowel, but appears to be a marker for the release of bacterial enzymes into the systemic circulation associated with breakdown of the normal bowel barrier to such materials. PMID- 3113164 TI - Why deferoxamine therapy predisposes to Yersinia sepsis. PMID- 3113165 TI - The cost-effectiveness of nursing practice. PMID- 3113166 TI - Cerebrovascular permeability to horseradish peroxidase in hypertensive rats: effects of unilateral locus ceruleus lesion. AB - Unilateral locus ceruleus lesion enhances leakage of radioiodinated human serum albumin into the ipsilateral cerebral cortex of rats with norepinephrine-induced hypertension. This ultrastructural study was undertaken, to determine the mechanism by which this permeability alteration occurs, using horseradish peroxidase (HRP) as a tracer. Unilateral locus ceruleus lesion was produced in male Wistar-Furth rats by stereotaxic microinfusion of 5 micrograms of 6 hydroxydopamine. Two weeks later, rats were injected with HRP intravenously and acute hypertension was induced in awake rats by an intravenous infusion of norepinephrine (6 micrograms), epinephrine (6 micrograms) or angiotensin amide (12 micrograms) given over a 2-min period. Thirty seconds later, the rats were perfused with fixative under deep anesthesia and their brains were sliced and processed for demonstration of HRP reaction product. Leakage of HRP occurred in both cerebral hemispheres in response to hypertension induced by the three pressor agents, but the leakage was greater on the lesioned side in response to epinephrine and norepinephrine, while in the case of angiotensin-induced hypertension side-to-side differences in permeability alterations were not observed. In both cerebral hemispheres increased permeability affected mainly arterioles, which showed enhanced pinocytosis as the principal mechanism of HRP extravasation. PMID- 3113167 TI - Demonstration of GM1-ganglioside in nervous system in generalized GM1 gangliosidosis using cholera toxin B subunit. AB - By using cholera toxin B subunit and its antibody, the deposition of GM1 ganglioside in the cerebral cortex and peripheral nerves including Meissner and Auerbach's plexuses in the intestine and other visceral nerves of generalized GM1 gangliosidosis was demonstrated. The GM1-ganglioside was found in the swollen neurons of cerebral cortex and ganglion cells of the peripheral nerves. Electron microscopically, parts of membranous cytoplasmic bodies, and amorphous substances among them, revealed a positive reaction for the cholera toxin staining. PMID- 3113169 TI - Otosclerosis and mucopolysaccharidosis. AB - By means of a literature review, clinical observations and temporal bone histopathology in the Hunter syndrome, we could show a reason for otosclerosis in childhood, a very rare observation. Therefore we do not believe that the presence of otosclerotic foci in temporal bones is mere coincidence in MPS II. It seems there is a causal connection between the generalized metabolic disorder and otosclerosis on the basis of enzyme deficiency. PMID- 3113168 TI - Capillary hemangioblastoma: histogenesis of stromal cells. AB - The histogenesis of stromal cells in capillary hemangioblastoma has been the subject of debate. The light and electron microscopic studies of hemangioblastomas presented here showed pericytic and leiomyoblastic features in stromal cells. Cells cultured by the monolayer method showed similar features to those of the original tumors. Immunohistochemical studies for glial fibrillary acidic protein and factor VIII/von Willebrand factor indicated that stromal cells were antigenically distinct from astrocytes and endothelial cells. These findings suggest that stromal cells are closely related to pericytes and smooth muscle cells, and support Rhodin's speculation that pericytes serve as a precursor to smooth muscle cells. PMID- 3113170 TI - Strial prostaglandins and leukotrienes. Biochemical characteristics and interrelationship with furosemide. AB - Synthesis of prostaglandins (PGs) was characterized in the lateral wall (LW) of guinea-pig cochlea. Basal synthesis at 37 degrees C was about 480 pg/LW (12.8 ng X mg-1 protein) for PGI2 and 85 pg/LW (2.3 ng X mg-1 protein) for PGE2, levelling out after 10 min of incubation. Incubation with arachidonic acid (10(-5) M) increased PGI2 and PGE2 synthesis by 44% and 1020%, respectively, showing that arachidonic acid availability is a synthesis-limiting factor. The stimulating effect of the Ca++ ionophore A23187 (5 X 10(-6) M) on PG synthesis was weak (about +50%) but was enhanced (about +140%) by preincubation with arachidonic acid. Angiotensin II (10(-6) M), vasopressin (5 X 10(-7) M), and furosemide (10( 8) to 10(-3) M) did not alter PG secretion. Neither aspirin nor indomethacin prevented the development of furosemide ototoxicity (endocochlear potential) in the rat. Perfusion with PGI2 influenced the furosemide effect in some instances. PMID- 3113171 TI - Angiographic difference in coronary artery of man, dog, pig, and monkey. AB - Comparative morphological studies on the coronary arteries of the left ventricular free wall were carried out on human, dog, pig, and monkey hearts by using postmortem coronary arteriography, soft X-ray photograms, and the clearing method. The results showed that the types of coronary arteries (types I, II, and III) and connecting portion of anastomotic vessels in the pig and monkey hearts closely resembled those in man. Whereas the dog hearts showed the following characteristics: numerous Type III vessels and anastomoses in the epicardial layer, the existence of only the left predominant type of coronary artery, and the supply of blood to the papillary muscles of the left ventricle mostly through a single branch of the coronary artery. Therefore, it is necessary to take into consideration the basic difference in the structure of the coronary arteries of human and dog hearts, when dogs are used experimentally for research of human ischemic heart disease. The fact that only the papillary muscles of the human heart-compared to animal hearts-are supplied blood from two sources may be advantageous to rescue the papillary muscles from ischemic necrosis. PMID- 3113172 TI - Genetic mucopolysaccharidoses, mannosidosis, sialidosis, galactosialidosis, and I cell disease. Ultrastructural analysis of cultured fibroblasts. AB - The cultured skin fibroblasts biopsied from 6 cases of galactosialidosis, 4 of I cell disease, 3 of Scheie syndrome and one of Sanfilippo B syndrome, Morquio A syndrome, sialidosis, and mannosidosis, respectively, were investigated electron microscopically to detect any cytoplasmic storage inclusions. In the cases of genetic mucopolysaccharidosis, vacuolar inclusions containing fine reticulogranular materials of low electron density predominated, showing no significant difference in fine structure among the Sanfilippo B syndrome, Scheie syndrome, and Morquio A syndrome. Similar storage inclusions were observed in sialidosis and mannosidosis and also revealed no obvious difference among the diseases and the above-mentioned syndromes of genetic mucopolysaccharidosis. In galactosialidosis, two types of inclusions, vacuolar and lamellar, were distinguished, resembling those usually seen in generalized gangliosidosis. In I cell disease, the cytoplasmic storage inclusions were variegated; vacuolar, concentric lamellar or osmiophilic amorphous. The availability of electron microscopy in tissue culture is discussed for making the diagnosis of these diseases, and the pathogenesis of lysosomal storage inclusions in the cultured cells of the diseases is briefly viewed. PMID- 3113173 TI - Foamy cells associated with phagocytosis of glutaraldehyde-treated red blood cells and red cell membranes. AB - In order to clarify the mechanism for the formation of foamy cells (macrophages with foamy appearance) associated with increased erythrophagocytosis, we tried to reproduce these cells in mice by subcutaneous injection of intact red blood cells (RBCs), OsO4-treated RBCs (Os-RBCs), glutaraldehyde-treated RBCs (G-RBCs), or isolated red cell membranes, and time-course observation was done by light and electron microscopy. Foamy cells were induced by the latter two methods. Within the macrophages, G-RBCs were fragmented into spherules by newly formed small vacuoles, and with time these spherules lost their hemoglobin content transforming into small vacuoles with translucent matrix. In most of these vacuoles, red cell membrane structure was discernible adjacent to the phagocytic vacuole. Such macrophages containing abundant small vacuoles appear foamy in light microscopy. Foamy cells induced by injection of red blood cell membranes were positive for lipid stains and contained abundant laminated membrane structures in electron microscopy. These results suggest that the foamy cells related with increased erythrophagocytosis are heterogeneous with respect to their pathogenesis and cellular inclusions, and proteinaceous constituents resistant to intracellular digestion are also responsible for the occurrence of foamy cells. PMID- 3113174 TI - Quantification of CD8-positive lymphocytes in lymph node follicles from HIV infected male homosexuals and controls. AB - The number of CD8-positive cells in follicular centres of hyperplastic lymph nodes from 20 Danish and Swedish homosexual men with persistent generalized lymphadenopathy and 43 control patients were enumerated in frozen tissue sections immunostained with monoclonal antibody reactive with the CD8-antigen ("cytotoxic suppressor" T-cell antigen). All the homosexuals were seropositive for HIV and histology showed changes characteristic of the early stage of HIV lymphadenitis. A significant increase (p much less than 0.001) of CD8-positive cells was demonstrated (mean 1,307 per mm2 follicular centre, SD 639) in HIV-related lymphadenopathy compared with the controls (mean 161 CD8-positive cells per mm2 follicular centre, SD 169). The results of this study show that the immunohistological demonstration of a significant increase of CD8-positive cells in the follicles of hyperplastic lymph nodes is suggestive of HIV-related lymphadenopathy. PMID- 3113175 TI - Synaptophysin--an immuno-histochemical marker for childhood neuroblastoma. AB - Synaptophysin, an integral membrane glycoprotein of presynaptic vesicles, was tested as an immuno-histochemical marker for childhood neuroblastoma. Synaptophysin immuno-reactivity was found in all neuroblastomas (6/6), but not in the other small round-cell tumors to be considered in its differential diagnosis. Thus, rhabdomyosarcomas (0/5), lymphomas (0/4), or Ewing's sarcomas (0/2) were negative for synaptophysin. The results suggest that synaptophysin is a useful marker for neuroblastoma, and it should belong to the marker panel used for the differential diagnosis of small round-cell tumors of childhood. PMID- 3113176 TI - [Studies on the synthesis of dihydrofolate reductase inhibitor, 5-(substituted phenyl)-thio(seleno)-2, 4-diaminopyrimidines and their inhibitory activity on L. casei and chicken liver DHFR]. PMID- 3113177 TI - The role of Ca2+ in hormonal imprinting of the Tetrahymena. AB - It is known from model experiments on Tetrahymena that primary exposure to a hormone induces receptor formation or amplification, in other words a hormonal imprinting. Substances acting on the intracellular Ca2+ level of the Tetrahymena, such as TMB-8, EDTA, EGTA, NiCl2 and La(NO3)3, interfered with hormonal imprinting of the unicellular to different degrees, and some of them influenced hormone (insulin, TSH) binding also independently of imprinting. Interference with the intracellular Ca-metabolism generally influenced imprinting by insulin and TSH, which were mediated by different mechanisms, to dissimilar degrees, or in opposite directions. On combined application of the agents acting on Ca metabolism, their effects were additive. It appears that intact Ca-mediation is an essential prerequisite for normal hormonal imprinting. PMID- 3113179 TI - Vertebrate cell culture I. PMID- 3113178 TI - Arterial hypoxia does not affect subchondral pressure and regional blood flow. AB - The influence of arterial hypoxia on bone marrow pressure, regional blood flow and oxygen and carbon dioxide tensions was investigated by simultaneous and continuous measurements in the femoral condyles of 8 rabbits. Arterial hypoxia was obtained by hypoventilation. The subchondral gas tensions and regional blood flow were measured by a previously described technique based on mass spectrometry. Arterial hypoxia caused a significant decrease in subchondral oxygen tension and an increase in subchondral carbon dioxide tension. There was no significant change in bone marrow pressure and regional blood flow. PMID- 3113180 TI - Immobilization of suspended mammalian cells: analysis of hollow fiber and microcapsule bioreactors. PMID- 3113181 TI - Rabies vaccine production in animal cell cultures. PMID- 3113182 TI - Production of tissue plasminogen activators from animal cells. PMID- 3113183 TI - Nerve and muscle cells on microcarriers in culture. PMID- 3113184 TI - Growth limitations in microcarrier cultures. PMID- 3113185 TI - Serum-free cultivation of lymphoid cells. PMID- 3113186 TI - Extraction and purification of arachidonic acid metabolites from cell cultures. PMID- 3113187 TI - Carbon dioxide transfer in biochemical reactors. PMID- 3113188 TI - Nutrition in acute renal failure. PMID- 3113189 TI - [Statistical study on PaCO2 as a risk factor in retinopathy of prematurity]. PMID- 3113190 TI - [The mechanism of corneal ring formation caused by endotoxin]. PMID- 3113191 TI - [Anti-neoplastic activity of a human recombinant tumor necrosis factor (Hu-rec TNF) alone or in combination with human recombinant gamma-interferon, doxorubicin or cis-platinum on a human renal cell carcinoma line]. AB - The inhibitory effect of human-recombinant tumor necrosis factor (Hu-rec-TNF) alone or in combination with human recombinant gamma-interferon (rec gamma-IFN), doxorubicin (ADM) or cis-platinum (CDDP) was studied for two human renal cell carcinoma lines (KO-RCC-1 and RCC-nu-1 cells). Hu-rec-TNF inhibited the cell growth of KO-RCC-1 cells in a dose- and time-dependent manner. The inhibitory effect was seen 48 hours after the treatment with Hu-rec-TNF alone. The effect of Hu-rec-TNF was cytotoxic in our experiment. On the other hand, Hu-rec-TNF did not inhibit the cell growth of RCC-nu-1 cells. There were sensitive and resistant cells in renal cell carcinoma. In KO-RCC-1 cells, Hu-rec-TNF enhanced the inhibitory effect of rec gamma-IFN, ADM or CDDP. On the other hand, Hu-rec-TNF did not enhance the inhibitory effect of rec gamma-IFN, ADM or CDDP in RCC-nu-1 cells. In our experiment, the combined treatment with Hu-rec-TNF and rec gamma IFN, ADM or CDDP was useful in human renal cell carcinoma which was sensitive for Hu-rec-TNF. PMID- 3113192 TI - [Primary transitional cell carcinoma of the male urethra: report of a case]. AB - A case of primary transitional cell carcinoma of the male urethra is reported. A 24-year-old man, who complained of tumor of the urethral orifice with hypospadias, was admitted to our Hospital on November 30, 1983. Urethrocystoscopy and biopsy revealed grade 1 papillary transitional cell carcinoma of the anterior urethra. Partial resection of anterior urethra including tumor was performed on December 20, 1983. Histopathological diagnosis revealed grade 2 transitional cell carcinoma without submucosal invasion. Postoperatively, the patient was treated with Tegafur and Krestin as adjuvant immuno-chemotherapy. The patient has shown no evidence of disease for 3 years after surgery. There have been reported 23 cases of primary transitional cell carcinoma of the male urethra in Japan. PMID- 3113193 TI - Aberrant right subclavian artery with a large diverticulum of Kommerell: a potential for misdiagnosis. PMID- 3113194 TI - Double-contrast examination of the colon with carbon dioxide: the use of effervescent powder. PMID- 3113195 TI - Atrial ventricular diverticulum: sonographic diagnosis. PMID- 3113196 TI - Quantitative determination of MS-induced corpus callosum atrophy in vivo using MR imaging. AB - To quantitate the extent of corpus callosum atrophy in multiple sclerosis, midsagittal corpus callosum areas were determined in 48 controls with normal MR scans and 41 patients with definite multiple sclerosis. The mean midsagittal corpus callosum area was 601 mm2 (range 405-791), 641 mm2, and 561 mm2 for all adult controls, for adult males, and for adult females, respectively. Control values were significantly greater than the means determined for all multiple sclerosis (MS) patients (508 mm2, range 281-758), for MS men (528 mm2), or for MS women (498 mm2). The degree of corpus callosum atrophy paralleled the estimated volume of periventricular and corpus callosum high-signal lesions, suggesting a possible cause-effect relationship. The results indicate that corpus callosum atrophy occurs commonly in patients with typical clinical forms of multiple sclerosis. PMID- 3113197 TI - Facial nerve enhancement in MR imaging. AB - The significance of facial nerve enhancement after IV gadolinium administration has not been determined. We evaluated the MR appearance of facial nerves (nonenhanced and enhanced) in patients without and with masses involving the temporal bone, internal auditory canal, or cerebellopontine angle. In patients without such masses, no facial nerve enhancement was seen. In the other group, four of 11 patients showed facial nerve enhancement and geniculate ganglion masses. Three of these four patients had neurofibromatosis; one had surgical verification of a facial nerve neurofibroma. Enhanced MR facilitates identification of abnormal facial nerves. PMID- 3113198 TI - Neuroepithelial cysts of the lateral ventricles: MR appearance. AB - The MR imaging appearance of neuroepithelial cysts in the lateral ventricle is reported. Two cases of proven and two of presumed intraventricular neuroepithelial cysts are presented. In one case, MR observations documented spontaneous regression of a large intraventricular cyst. Theories regarding the origin of neuroepithelial cysts are briefly reviewed. Standard T1- and T2 weighted spin-echo pulse sequences were used to study cysts in the lateral ventricles in axial, coronal, and sagittal planes. The cyst wall can be demonstrated reliably with MR images, eliminating the need for CT and/or contrast ventriculography. MR may also be useful in monitoring cyst size on serial examinations. PMID- 3113199 TI - Mycotic aneurysm in angiitis associated with herpes zoster ophthalmicus. AB - Varicella zoster (VZ) is an unusual cause of CNS angiitis, usually occurring in older patients and immunocompromised hosts. The infection most commonly presents as herpes zoster ophthalmicus with contralateral hemiplegia. Mycotic aneurysm formation associated with VZ angiitis is rare. We report two cases of VZ angiitis with mycotic aneurysm formation (both aneurysms eventually ruptured) and one case of probable VZ angiitis with distal carotid occlusion and cerebral infarction. The CT and angiographic appearances, clinical course, and histopathology are presented. PMID- 3113201 TI - Posttraumatic ethmoidal pseudomeningoencephalocele. AB - Three cases are presented that illustrate the potential of craniofacial trauma to generate pseudomeningocele formation in the region of the ethmoidal air cells. In each case there was the further association of herniation of cerebral substance through the chronic diastatic fracture resulting in an acquired encephalocele. Contrast cisternography showed this important combination of anatomic findings and aided in planning the subsequent reparative surgery. PMID- 3113200 TI - CT findings in spinocerebellar degeneration. AB - Thirty-five CT scans were studied from patients with several forms of spinocerebellar degeneration. Atrophy was determined by objective measurements of the number and width of cerebellar sulci, transverse diameter and surface area of the fourth ventricle, brainstem ratio, cerebellopontine angle cistern, and Evans' index. Two-thirds of the patients with Friedreich's ataxia showed moderate cerebellar atrophy and an increase in the surface area of the fourth ventricle. Severe cerebellar atrophy and enlargement of the cerebellopontine angle cistern was seen in patients with olivopontocerebellar (OPC) atrophy and idiopathic cortical cerebellar atrophy. In the OPC atrophy group there was also prominent atrophy of the brainstem and an increase in the fourth ventricle parameters. Alcoholic cerebellar degeneration showed a specific pattern of cerebellar atrophy most prominent in the superior vermis, together with a slight increase in the fourth ventricle surface, a reduction in the size of the brainstem, and an enlargement of the cerebellopontine angle cistern. Supratentorial atrophy was present only in the OPC and alcoholic atrophy groups. In one patient with spastic ataxia, CT was normal but MR imaging revealed prominent atrophy of the spinal cord. These CT patterns appear to be distinctive enough to permit the diagnosis and classification of the various forms of spinocerebellar degeneration. PMID- 3113202 TI - Difficulties in diagnosing congenital posterior fossa fluid collections after shunting procedures. AB - The differential diagnosis of retrocerebellar fluid collections in infants is important because of the prognostic implications. Usually the diagnoses are easy; however, shunting of the lateral ventricles or of the fluid collections may alter the appearance of the lesions, precluding accurate diagnosis. Under such circumstances a careful study of all the sequential radiologic studies is necessary. PMID- 3113203 TI - Cerebral venous distention associated with cardiac failure in infants. AB - Three infants with congestive cardiac failure demonstrated dilated and hyperdense intracranial veins and sinuses on noncontrast cranial CT. Intracranial venous thrombosis and arteriovenous malformation were excluded in two infants by autopsy and in one infant by MR imaging. We believe the CT findings were secondary to an elevated central venous pressure caused by the cardiac failure. This CT pattern suggests venous congestive failure, and it should alert the clinician and radiologist to the risk of subsequent sinus thrombosis. PMID- 3113204 TI - Erroneous sonographic identification of fetal lateral ventricles: relationship to the echogenic periventricular "blush". AB - We show, through correlation of fetal, neonatal, and necropsy brain sonography, that the three-parallel-echogenic-line configuration classically thought to represent fetal lateral ventricular margins on high axial images are actually extraventricular, lying within cerebral white matter. Accurate sonographic identification of fetal hydrocephalus is essential for appropriate patient management. Both qualitative and quantitative methods of determining ventriculomegaly have been described. The latter require identification of lateral ventricular walls for subsequent ventricular mensuration and comparison with hemispheric width. The parallel-line configuration, thought to represent ventricular margins, has been used for such measurements. We have--through careful fetal, neonatal, and necropsy specimen scanning in several planes- determined that the presumed ventricular wall echoes are actually extraventricular, arising from fibers within the cerebral white matter aligned perpendicular to the sonographic beam. This is identical to the etiology of the normal echogenic periventricular "blush" described in the neonate. Since these parallel echogenic lines do not represent actual ventricular margins, they should not be relied upon for the diagnosis of ventriculomegaly. PMID- 3113205 TI - Myelographic study of the spinal cord ascent during fetal development. AB - To assess the length of the spinal cord relative to the vertebral column during fetal development, we performed translumbar myelograms on 340 spontaneously aborted fetuses. Of these, 146 were selected for study. There were 76 males and 70 females, with fetal age ranging from 7 to 33 weeks. Significant variation in the level of spinal cord termination was found in fetuses between 12 and 25 weeks gestational age. In fetuses between 25 and 33 weeks gestational age, the cord ended at or above the third lumbar vertebra. PMID- 3113206 TI - Effects of i.v. contrast administration on intraspinal and paraspinal tissues: a CT study. 1. Measurement of CT attenuation numbers. AB - Contrast-enhanced CT can be useful in differentiating between recurrent disk herniation and scar formation after disk surgery. Thirty such CT studies were assessed retrospectively to determine the utility of CT attenuation measurements in identifying intraspinal pathology. Measured values of intraspinal tissues, but also of "reference" materials such as CSF, blood, and muscle tissue, showed large individual variations; and enhancement patterns for recurrent herniation and scar formation were not specific. The chief value of contrast administration may lie in the clearer definition that is gained of various structures within the postoperative spine. PMID- 3113208 TI - MR of venous sinus thrombosis: a case report. PMID- 3113207 TI - CT diagnosis of an atypical nasopharyngeal teratoma in a newborn. PMID- 3113209 TI - Persistent cortical enhancement in tuberculous meningitis. PMID- 3113210 TI - Transdural herniation of the cervical spinal cord as a complication of a broken fracture-fixation wire. PMID- 3113211 TI - CT myelography of extradural pigmented villonodular synovitis. PMID- 3113212 TI - Intraoperative sonography of a spinal cord arteriovenous malformation. PMID- 3113213 TI - MR in the diagnosis of multiple sclerosis. PMID- 3113214 TI - Leukoencephalopathy in normal and pathologic aging. PMID- 3113215 TI - CT changes in dementing diseases. PMID- 3113216 TI - Wristwatch magnetization and demagnetization in MR installations. PMID- 3113217 TI - Sturge-Weber syndrome with extensive intracranial calcifications contralateral to the bulk of the facial nevus, normal intelligence, and absent seizure disorder. PMID- 3113218 TI - Pseudoforamina of the skull base: a normal variant. PMID- 3113219 TI - An unusual CT appearance of lupus cerebritis. PMID- 3113221 TI - Change in chromatogram patterns after volatilization of some aroclors, and the associated quantitation problems. AB - PCBs with the highest vapor pressures (fewest chlorines) in Aroclors 1016, 1242, 1254 and 1268 were enriched in the vapor phase relative to the original Aroclor during volatilization from a glass surface for up to 8 hr. PCBs with the lowest vapor pressures (most highly chlorinated) were enriched in the corresponding residue. Thus, visual matching of gas chromatograms with those of Aroclor standards may not be sufficient to identify a specific Aroclor since the past history of a sample is often unknown. The enrichment also was detected using isomeric classes, but not using total chlorine content. The perchlorination method and the Webb-McCall method using all chromatographic peaks agreed quantitatively; this was not always so for the NIOSH multiple peaks and the Webb McCall methods. PMID- 3113220 TI - The immunological events leading to the "in vitro" response to PPD. AB - In normal individuals the 5/9 monoclonal antibody (5/9 MAb) recognizes a T-cell fraction that includes all T lymphocytes with inducer activities. Here, circulating 5/9+ and 5/9- T lymphocytes were isolated from tuberculim skin positive subjects and the proliferative response induced by PPD was investigated. The results show that the total PPD-induced lymphocyte DNA synthesis is confined to the 5/9+ T cell fraction. PPD was unable to induce a direct or indirect (through the 5/9+ cells) proliferation of T8+ cells. Whether 5/9 antigen, expressed on the PPD responsive T-cell subset, is involved in PPD-induced cell proliferation, was also analyzed. No significant effect was observed adding 5/9 MAb, whereas complete inhibition of antigen-induced blastogenesis was observed upon addition of a MAb (D1.12) directed to common determinants of Ia antigens. The supernatant fluids of 5/9+ and 5/9- cells stimulated with PPD were studied for the presence of IL-2 and IFN-gamma. Production of both these lymphokines was detected in the 5/9+ T-cell supernatants, whereas neither IL-2 or IFN-gamma were found in supernatants of 5/9- cells. In addition, preliminary experiments suggested that only the supernatants of PPD-stimulated 5/9+ T cells were able to activate a macrophage cell line, inducing a remarkable release of hydrogen peroxide. These results indicate that the lymphocyte responsiveness to PPD is confined in a small T cell fraction, expressing the 5/9 antigen; only these T cells are able to release soluble factors (i.e., IL-2 and IFN-gamma); those or other soluble factor(s) produced in PPD-stimulated cultures seem able to activate the macrophages. PMID- 3113222 TI - Acute coronary thrombolysis with recombinant human tissue-type plasminogen activator: initial patency and influence of maintained infusion on reocclusion rate. AB - An intravenous infusion of 40 mg of recombinant tissue-type plasminogen activator (rt-PA) was given intravenously over 90 minutes to 123 patients with acute myocardial infarction (AMI) of less than 4 hours' duration. A coronary angiogram was recorded at the end of the infusion in 119 patients. Central assessment of the angiograms revealed a patent infarct-related artery in 78 patients (patency rate 66%, 95% confidence limits 57 to 74%). Patients with a patent infarct related artery at the first angiogram were randomized in a double-blind manner to receive a subsequent 6-hour infusion of either 30 mg of rt-PA or placebo. All patients had received an initial bolus of 5,000 IU of heparin and then 1,000 IU/hour until a second angiogram was recorded 6 to 24 hours after the start of the second perfusion. At central assessment of the second coronary angiogram the reocclusion rate was 2 of 36 patients who received rt-PA at the second infusion and 3 of 37 patients not receiving this drug (or the 2 groups combined 7%, 95% confidence limits 2 to 15%). Three of 60 patients (5%, 95% confidence limits 1 to 14%) with patent arteries on both previous angiograms had a later occlusion as judged on the angiogram recorded at hospital discharge. No difference in late reocclusion rates between the 2 treatment groups was observed. PMID- 3113223 TI - Prevention of tolerance to nitroglycerin patches by overnight removal. AB - This investigation assesses the extent of tolerance development with nitroglycerin patches and whether tolerance might be prevented by overnight patch removal. On commencing therapy, active patches significantly prolonged exercise time (3.5 hours after patch application) in comparison with placebo, with an accompanying reduction in ST-segment depression at maximal common workload. Patients then received continuous or 12-hour-daily intermittent patch therapy, in a double-blind fashion, for 7 days. Exercise testing was repeated before and after active patch application, on the eighth day of each treatment phase. During continuous therapy, beneficial effects on exercise time and ST depression were abolished. By contrast, during intermittent therapy, prolongation of exercise time and reduction in ST-segment depression still occurred, on testing 3.5 hours after active patch application. These results confirm previous studies showing a high degree of tolerance during continuous therapy with nitroglycerin patches and suggest that tolerance can be prevented by 12-hour-daily intermittent therapy. PMID- 3113224 TI - Determinants of hospital cost and length of stay for patients undergoing electrophysiologic testing. AB - To assess the effects of various clinical factors in determining the cost and length of stay in patients undergoing electrophysiologic testing for cardiac arrhythmias, the hospital cost and length of stay data were reviewed in 222 consecutive inpatients who underwent electrophysiologic testing from January 1 to December 31, 1984. Admissions were classified as: primarily for treatment of arrhythmias (171 patients); primarily for treatment of arrhythmias but with serious concurrent illnesses that prolonged hospitalization (43 patients); or primarily for nonarrhythmic problems with electrophysiologic study an incidental part of hospitalization (8 patients). Based on allowable length of stay for the applicable DRGs, actual hospitalizations exceeded Medicare allowable length of stay by 50 to 500%. Retrospective review of hospital charts indicated that 3 clinical factors serve as effective markers in determining length of stay: need for amiodarone, induction of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), and presence of serious other medical problems that require stabilization before electrophysiologic testing. Our data indicate that 3 classes of patients can be identified: I. DRG A (45%)--those who did not have sustained VT or VF induced, did not require amiodarone and had no serious concurrent illnesses. The mean length of stay was 7.1 days. II. DRG B patients (21%)--those who had sustained VT or VF induced, but did not require amiodarone and had no serious concurrent illnesses. The mean length of stay was 13.7 days. III. DRG C patients (34%)--those who either had a serious concurrent illness or required amiodarone. The mean length of stay was 19.7 days. This classification schema might allow a more appropriate system for determining reimbursement. PMID- 3113225 TI - Usefulness of intravenous thrombolytic therapy with pro-urokinase in acute myocardial infarction. PMID- 3113226 TI - Presence of abundant filaments in apical caps of the nonciliated bronchiolar epithelial (Clara) cells. AB - The nonionic detergent Triton X-100 has often been used for the extraction of cytoplasmic materials. We used the detergent in a vascular perfusion medium when preparing rat lung in order to observe the cytoskeleton of the nonciliated bronchiolar epithelial (Clara) cells. To eliminate some cytoplasmic materials selectively and to maintain good fine cell structure simultaneously, the lungs were perfused sequentially with the detergent (0.2% Triton X-100) alone for 2 min, with a mixture of low-concentration (0.1%) glutaraldehyde and detergent (0.2% Triton X-100) for 15 min, and finally with 2.5% glutaraldehyde for 5-10 min. After fixation, the nonciliated bronchiolar epithelial (Clara) cells were observed by scanning and transmission electron microscopy. At the apical region of the cells, there were central cytoplasmic protuberances (apical caps) filled with microfilaments. These filaments were bound at one end to the cytoplasmic side of the cell membrane and ran into the interior of the cytoplasm at the other end. As a control, the Clara cells were observed by transmission electron microscopy after perfusion with 2.5% glutaraldehyde solution. The luminal surfaces of the cells were covered with short, thick microvilli. The apical caps also had microvillus-like protrusions. These results suggest that the apical cap is not an apocrine droplet but rather is a stable structure involved in the function of the Clara cells. PMID- 3113227 TI - Thermogenic and nitrogen response to submaximal exercise in parenterally repleted normal man. AB - To determine whole-body energy and nitrogen responses to submaximal exercise during repletion levels of intravenous feeding (IVF), five normal male volunteers were hospitalized and underwent serial changes in nutritional intake consisting of weight-maintaining oral feeding (4 d), starvation (10 d), and weight increasing parenteral feeding (10 d). Twelve-hour aliquots for urinary nitrogen, creatinine, and 3-methylhistidine were collected during the final 36 h of oral feeding and IVF. During these experimental periods, indirect calorimetry was utilized to determine resting oxygen consumption and that occurring during a 1-h period of submaximal (40% of maximal) upright, bicycle exercise. Despite differences in the route of nutrient delivery, oxygen uptake during a fixed rate of exercise (75 W) was similar during oral (16.7 +/- 0.4 mL X kg-1 X min-1) and IVF (14.7 +/- 1.0 mL X kg-1 X min-1). When compared with basal urinary losses, submaximal exercise resulted in diminished nitrogen (p less than 0.01, oral) and 3-methylhistidine (p less than 0.05, oral; p less than 0.01, IVF) excretion during a 12-h post-exercise recovery period. PMID- 3113228 TI - Breath pentane analysis as an index of lipid peroxidation: a functional test of vitamin E status. AB - Pentane, which evolves from the reaction involving omega-6 fatty acids, is a good index of lipid peroxidation. We describe a method for measuring breath pentane excretion in adult humans. After a 4-minute washout period, expired air was analyzed by gas chromatography. Breath was passed through a cooled loop of alumina to adsorb, concentrate, and release, on heating, pentane. Pentane was analyzed by a Porasil-D column with a derived calibration curve. The mean excretion of pentane in 10 normal adults was 6.34 +/- 0.96 pmol X kg-1 X min-1 (mean +/- SEM) and was significantly higher in five patients with plasma vitamin E deficiency (15.39 +/- 1.84 pmol X kg-1 X min-1). There was a significant negative correlation between pentane output and plasma vitamin E levels (r = 0.66, p less than 0.01). Moreover, breath pentane excretion was significantly decreased after a 10-d supplementation with vitamin E in five normal subjects. We conclude that breath pentane output is a sensitive, noninvasive, functional test for assessing vitamin E status. PMID- 3113229 TI - Monoclonal antibodies: prospects for specific immunotherapy for gliomas. AB - Monoclonal antibodies produced by hybrids of lymphoid cells can be raised against cancer cells. These antibodies can be used to detect certain cancers, and some monoclonals bind with relative selectivity to glioma-associated antigens. Various laboratories are studying the radiolocalization of human glioma antigens in tumor cells transplanted into animals, and this imaging technique is also being tested in patients. Methods have been developed to promote passage of these antibodies across the blood-brain barrier, and thereby, to increase their uptake in tumors. Either alone or in conjunction with macrophages, cytotoxins, or radiosensitizers, these antibodies may offer a high degree of selective tumor destruction with relative sparing of normal brain. PMID- 3113230 TI - Kallikrein inhibition and C1-esterase inhibitor levels in patients with the lupus inhibitor. AB - It has been suggested that kallikrein inhibition may predispose patients with the lupus inhibitor to thrombosis by interfering with the Factor XII-mediated activation of plasminogen. To further investigate this suggestion, the authors measured kallikrein inhibition in 19 patients with the lupus inhibitor. They found that kallikrein inhibition was greater than 100% of that of a normal plasma pool in all patients and greater than 125% in 11 of 19. Kallikrein inhibition was significantly correlated with C1-esterase inhibitor (C1S-INH) concentration, which they measured by rocket immunoelectrophoresis (r = +0.55, P less than 0.05). In three patients the C1S-INH was more than 30% greater than the kallikrein inhibition. Crossed immunoelectrophoresis for C1S-INH in these patients' plasma revealed an electrophoretic mobility identical with that of the normal plasma pool. The authors suggest that C1S-INH-mediated kallikrein inhibition, in conjunction with other coagulation abnormalities, predisposes patients with the lupus inhibitor to thrombosis. PMID- 3113231 TI - The hazards of benign(?) neglect of elevated blood lead levels. PMID- 3113232 TI - Lack of effect of lithium carbonate in patients with glycogenosis Ib. AB - Lithium carbonate has been observed to induce neutrophilia in psychiatric patients and has been used in a number of childhood neutropenic disorders. We tried lithium carbonate in three children with glycogenosis Ib to see if the drug would alleviate the neutropenic complications of the disorder. Mean absolute neutrophil counts rose in one patient but not in the other two. Despite high dosage schedules, serum lithium levels were highly erratic. Two patients developed potentially severe side effects, including polyuria, diarrhea, and altered mental status. One patient developed pneumonia despite a neutrophil count rise in response to therapy. Lithium carbonate is not useful in patients with glycogenosis Ib. PMID- 3113233 TI - Cancer in patients receiving long-term dialysis treatment. AB - A large excess of non-Hodgkin's lymphoma has been documented in renal transplant patients and may be related to immunosuppressive therapy, persistent antigenic challenge from the graft, or both. To determine whether immuno-suppression resulting from chronic renal failure is associated with an elevated risk of certain tumors such as non-Hodgkin's lymphoma, the authors studied cancer incidence in a national cohort of 28,049 patients in the United States with chronic renal failure who received maintenance dialysis for at least six months (totaling 66,706 person-years of observation). Compared with national incidence rates, the relative risk (RR) of cancer was 0.9 (excluding nonmelanoma skin cancer, multiple myeloma, kidney cancer, and uterine cervix cancer). Moderate excesses of leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, thyroid cancer, and biliary tract cancer were found, but were not statistically significant for both sexes combined. A significantly elevated risk of non-Hodgkin's lymphoma among patients with chronic glomerulonephritis (RR = 2.6) accounted for the excess observed in the total series, raising the possibility of factors specific to this disease. PMID- 3113234 TI - A cost-effectiveness analysis of measles outbreak control strategies. AB - This study compares the cost-effectiveness of six vaccination strategies during a measles outbreak: vaccination of all susceptibles 15 months of age or older and born after 1956 (the current routine strategy); lowering the recommended age at vaccination from 15 to 12 months (plus current routine strategy); lowering the recommended age at vaccination to six months (plus current routine strategy); revaccination of those vaccinated at 12-14 months of age (plus current routine strategy); vaccination of all students in school regardless of immune status; and vaccination of all residents 15 months to 28 years of age in the community regardless of immune status. The analysis is based on the hypothetical, early application of these strategies to a 1985 measles outbreak in Montana, which occurred despite appropriate application of current prevention and control recommendations. Although the results are applicable only to this particular outbreak, this analysis provides an approach which can be used in other settings to assess measles outbreak control strategies. Similar studies would need to be performed in a variety of settings to determine the most cost-effective measles outbreak control strategies overall. PMID- 3113235 TI - Snow Mountain agent gastroenteritis from clams. AB - A 1983 investigation of two clambake-related gastroenteritis outbreaks in Rochester, New York, showed that 84 (43%) of 196 persons interviewed had an acute illness characterized by watery diarrhea, vomiting, and abdominal cramps. None of the ill persons were hospitalized or had complications. Illness was associated with eating raw (p = 0.002) or baked (p less than 0.01) hard-shell clams, with the risk of illness increasing with the total number of clams consumed (p less than 0.01). The median incubation period and duration of illness were 36 and 44 hours, respectively. Stool samples obtained 2-4 days after onset of illness were negative for commonly recognized bacterial and viral pathogens. However, of 31 persons whose stools were tested, the stool of only one ill person was positive by enzyme-linked immunosorbent assay for the Snow Mountain agent, one of the Norwalk-like viruses. Paired serum specimens from six (67%) of nine ill and two (29%) of seven well persons showed a fourfold or greater rise in antibody titer to Snow Mountain agent. Persons who ate clams were more likely to seroconvert to Snow Mountain agent (eight of 12) than were those who did not eat clams (zero of four) (p = 0.04). The clams were harvested off the coast of southern Massachusetts in late October, when harvest waters were documented to be contaminated by untreated municipal sewage. This report describes the first documented outbreak of shellfish-associated gastroenteritis attributed to Snow Mountain agent of which we are aware. PMID- 3113237 TI - Achieving parenteral nutrition cost savings through prescribing guidelines and formulary restrictions. AB - A hospital's use and pharmacy costs of parenteral nutrition (PN) therapy before and after implementation of standardized PN formulas, prescribing guidelines, and preprinted order forms were compared. The study hospital, a large teaching institution, did not have a formal PN team. Guidelines for prescribing were promulgated by the pharmacy and therapeutics committee, the quality assurance committee, and the medical staff executive committee. Records of all patients receiving PN therapy were audited for six-month periods before and after implementation of the program. Cost data associated with decreased PN and albumin wastage, reduced labor and materials costs, inventory reduction, decreased inventory holding costs, and competitive bidding were analyzed. After implementation of this program, the number of wasted PN solutions was reduced by 55.8%, and the cost of PN solutions decreased by 36.9%. Use of albumin-containing PN solutions was reduced by 85.3%. PN solution preparation times were reduced by 66.1% (a reduction of 58.7% in preparation costs), and PN acquisition costs were reduced by 54.5%. A total annual savings of $170,722 was realized, plus a one time cost savings of $15,632 from inventory reduction. Use of standardized parenteral nutrition formulas and prescribing guidelines can substantially decrease the cost of patient care. PMID- 3113236 TI - Two murine monoclonal antibodies to peripheral blood monocyte differentiation antigens discriminate within M5 acute non-lymphoid leukemia (ANLL) cells. AB - Two murine monoclonal antibodies (MoAbs), LAM3 and LAM7 of the IgG1 isotype, which were produced by immunization with normal peripheral blood monocytes (PBM), were assayed in their specificity by indirect immunofluorescence against a panel of normal as well as leukemic cells. Both LAM3 and LAM7 were reactive with PBM while LAM3 also recognized platelets. Neither MoAb showed reactivity with erythrocytes, granulocytes, or resting and mitogen activated B and T lymphocytes. The reactivity with bone marrow cells correlated with the degree of monocyte contamination. Among the 62 cases of leukemia tested, which included three cases of B-CLL, 19 cases of ALL, and 40 cases of ANLL, both MoAbs reacted highly homogenously only with M5b ANLL cells. These findings indicate that the two MoAbs, which recognize two distinct epitopes, represent useful markers in the differential diagnosis of M5b ANLL. PMID- 3113238 TI - Calcium and phosphate solubility in neonatal parenteral nutrient solutions containing Aminosyn PF. AB - Factors affecting the solubility of calcium and phosphate in neonatal total parenteral nutrient (TPN) solutions containing a new amino acid formulation were studied. Six TPN solutions containing various concentrations of Aminosyn PF, an amino acid solution for infants and children, were prepared in 10% dextrose injection. Some of the solutions also contained cysteine hydrochloride 40 mg per gram of protein. Various concentrations of calcium gluconate and monobasic and dibasic potassium phosphate were added to 20-mL samples of the TPN solutions. A total of 27 samples of each TPN solution was prepared. Samples were visually inspected after 18 hours at 25 degrees C and again after 30 minutes in a water bath at 37 degrees C. Clear samples at this time were also examined microscopically. Solubility curves were prepared by plotting the concentrations at which either visual or microscopic precipitation occurred. Solubility curves for TPN formulations containing Aminosyn PF revealed a decrease in calcium solubility of 5 to 15 meq/L and a decrease in phosphate solubility of 5 to 15 mmol/L compared with previously published calcium-phosphate solubility curves for another similar amino acid solution, TrophAmine. Calcium and phosphate solubilities were also influenced by temperature and the time after solution preparation. In these TPN formulations containing Aminosyn PF as the amino acid source, the solubilities of calcium and phosphate were substantially less than reported in a previous study of solutions containing TrophAmine. PMID- 3113239 TI - Effect of the prospective-pricing system on drug use in Medicare patients in Georgia long-term-care facilities. PMID- 3113240 TI - Misoprostol-induced changes in gastric mucosal hemodynamics. A double-blind parallel study in human volunteers. AB - The effects of misoprostol on human gastric mucosal hemodynamics were examined in a double-blind, placebo-controlled, parallel study in 12 healthy male volunteers. Six subjects received 200 micrograms of misoprostol and six received placebo. The index of mucosal blood volume and mucosal blood hemoglobin oxygen saturation (Hb SO2) were measured at 20 locations in the stomach using reflectance spectrophotometry during endoscopy prior to and after administration of the study drug. Mucosal blood volume index increased by approximately 10 to 25 percent throughout the stomach without a significant change in mucosal Hb-SO2 following treatment with misoprostol. The increase in mucosal blood volume index was statistically significant for 16 of the 20 locations (p less than or equal to 0.05). Placebo produced no significant change in mucosal blood volume and mucosal Hb-SO2. These findings suggest that misoprostol may have the potential effect of accelerating gastric ulcer healing by improving gastric mucosal hemodynamics, in addition to its gastric acid antisecretory activity. PMID- 3113241 TI - Antisecretory and mucosal protective actions of misoprostol. Potential role in the treatment of peptic ulcer disease. AB - Misoprostol, a synthetic methyl ester analogue of prostaglandin E1, inhibits basal, nocturnal, and stimulated gastric acid secretion. In doses of 400 to 1,200 micrograms daily, misoprostol accelerates the healing of duodenal and gastric ulcers in humans. In addition to its antisecretory actions, misoprostol has gastroduodenal mucosal protective (cytoprotective) effects in animals and in humans. In humans, these cytoprotective actions have been demonstrated in acid dependent studies using non-antisecretory doses and in acid-independent studies using antisecretory doses. Patients with peptic ulcer disease may have a relative deficiency of mucosal prostaglandin synthesis as compared with nonulcer control subjects. In addition, patients who consume nonsteroidal anti-inflammatory drugs and those who are cigarette smokers may also have depressed gastric mucosal prostaglandin synthesis. There is some evidence that misoprostol reverses the deleterious effect of smoking on duodenal ulcer healing and that it is effective in treating and preventing mucosal damage induced by nonsteroidal anti inflammatory drugs and alcohol. PMID- 3113242 TI - Comparative efficacy of misoprostol and cimetidine in the treatment of acute duodenal ulcer. Results of major studies. AB - Misoprostol, a synthetic methyl ester of prostaglandin E1, has been shown to possess potent antisecretory activity in addition to a mucosal protective effect. Several multicenter double-blind, placebo-controlled trials confirmed the efficacy of misoprostol in the treatment of duodenal ulcer when administered at 800 micrograms in two or four divided doses daily. This report summarizes three cimetidine-controlled trials conducted in three separate geographic areas (Europe, Argentina, and Japan). The trials were double blind, randomized, and endoscopically controlled. In all studies, healing was defined as the absence of ulcer on endoscopy. The efficacy of misoprostol in the treatment of duodenal ulcer was shown to be equivalent to that of the histamine H2-receptor antagonist. In the Argentine study, the rate of disappearance of mucosal erosions was significantly greater for misoprostol than for cimetidine. Misoprostol was well tolerated. Mild and transient diarrhea not necessitating treatment or withdrawal occurred in 4 to 9 percent of the misoprostol-treated patients. These results indicate that misoprostol has a unique anti-ulcer action and represents a significant addition to the physician's armamentarium in the total medical management of duodenal ulcer. PMID- 3113243 TI - Gastric protection by misoprostol against 1,300 mg of aspirin. An endoscopic dose response study. AB - Misoprostol at a dose of 200 micrograms inhibits gastric acid secretion and protects the gastric mucosa against the injurious effects of a single 1,300-mg dose of aspirin. The purpose of this study was to determine whether lower subantisecretory doses of misoprostol protect the gastric mucosa in this single dose aspirin model. Protection was defined as no more than 10 hemorrhagic spots and no more than two hemorrhagic streaks. A total of 140 men participated in the two phases of the study. In the first phase, groups of 10 subjects each received placebo or misoprostol in doses of 200 micrograms, 100 micrograms, 50 micrograms, or 25 micrograms in a double-blind design. All misoprostol doses protected 50 to 70 percent of subjects as compared with 20 percent of subjects in the placebo group. To expand the number of observations, 90 additional subjects in groups of 30 each were evaluated after receiving misoprostol 50 micrograms or 25 micrograms or placebo. Misoprostol 50 micrograms protected 14 of 30 subjects (47 percent), 25 micrograms protected 11 of 30 (37 percent), and placebo protected six of 30 (20 percent). The dose-response trend was statistically significant (p less than 0.05). It is concluded that misoprostol protects the gastric mucosa against a single 1,300-mg dose of aspirin and that there is a significant dose-response relationship. PMID- 3113244 TI - Protection by misoprostol against naproxen-induced gastric mucosal damage. AB - The protective effect of misoprostol against naproxen-induced gastric mucosal damage was the subject of a double-blind, randomized, parallel-group study. Thirty-two healthy subjects were treated with naproxen 500 mg twice daily and either misoprostol 200 micrograms or matching placebo twice daily for seven days. Gastroscopy was performed before and after the treatment period and the mucosa was assessed for erosive and petechial lesions according to a predetermined scoring scheme. Of 25 evaluable subjects, 12 were treated with misoprostol and 13 were treated with placebo. The mean overall endoscopic score was 1.24 +/- 0.09 with placebo and 0.26 +/- 0.07 with misoprostol. The difference, 0.98, was highly significant (p less than 0.001), with 95 percent confidence limits of 0.74 to 1.22. All subjects in the placebo group had higher mean scores than any in the misoprostol group. The scores for erosive and bleeding lesions in the antrum and corpus/fundus of the stomach were all reduced by administration of misoprostol. In conclusion, the results clearly demonstrate that misoprostol protects the gastric mucosa of humans against naproxen-induced damage. PMID- 3113245 TI - Role of misoprostol in reducing aspirin-induced gastrointestinal blood loss in arthritic patients. AB - Nonsteroidal anti-inflammatory drugs are used to control pain and inflammation in arthritic disorders. When used at recommended anti-inflammatory dose levels, however, they often produce injury to the gastric and duodenal mucosa and concomitant blood loss. A double-blind, parallel, placebo-controlled study was conducted to assess the effectiveness of misoprostol, a synthetic analogue of prostaglandin E1, in preventing gastrointestinal blood loss induced by acetylsalicylic acid in patients with degenerative joint disease. Forty-five arthritic patients (22 women and 23 men) were admitted to the study. All patients had received treatment with 3,900 mg of acetylsalicylic acid per day in four divided doses for at least two weeks and continued to receive that regimen for the duration of the study. Red blood cells were tagged with chromium-51, and fecal blood loss was determined from Days 4 to 7. Patients with a mean blood loss of at least 1.5 ml per day were randomly allocated to receive either placebo or 200 micrograms of misoprostol four times daily for seven days. Fecal blood loss was measured daily, and the results were compared with baseline determinations. Of 41 patients who completed the study, 19 were treated with misoprostol. Of these, 11 patients (57.9 percent) had at least a 50 percent reduction in blood loss. Of 22 patients receiving placebo, only one had a 50 percent reduction in blood loss (p = 0.003; Fisher's exact test). Mean blood loss in patients using misoprostol was reduced from 3.65 +/- 2.51 to 1.57 +/- 0.86 ml per day, whereas among those taking placebo, mean blood loss did not significantly change (2.98 +/ 1.24 to 2.79 +/- 1.63 ml per day). The difference in blood loss between the misoprostol and placebo groups was significant (p = 0.0023; Wilcoxon test). In those patients who completed the study, no significant changes were detected on laboratory tests. In conclusion, misoprostol effectively reduced fecal blood loss in arthritic patients treated with acetylsalicylic acid. PMID- 3113246 TI - Humanitarian use of misoprostol in severe refractory upper gastrointestinal disease. AB - Misoprostol was provided on a humanitarian basis to 157 patients with severe, often life-threatening, refractory upper gastrointestinal (UGI) disease not managed by available medical therapy (cimetidine, ranitidine, antacids, sucralfate, and/or prior surgery). A total of 162 separate clinical treatment courses were evaluated in the 157 patients for the period May 1, 1981 to May 6, 1986. Misoprostol was administered orally or via nasogastric tube, 800 micrograms to 1,200 micrograms daily in four to six divided doses, for periods of from one day to 17 months. Patients were considered to have a favorable clinical outcome if they achieved significant improvement in symptoms, hemorrhagic status, or appearance of their condition on endoscopy. Favorable clinical outcomes were observed in 52 of 83 treatment courses (63 percent) involving UGI hemorrhage and in 44 of 79 treatment courses (56 percent) for long-standing nonhemorrhagic UGI disease. A total of 116 treatment courses were for patients with a single UGI entry diagnosis; 28 treatment courses were for patients with two UGI entry diagnoses; four courses were for patients with three UGI entry diagnoses; and 14 treatment courses were for miscellaneous UGI entry diagnoses. Treatment outcomes were analyzed by the four most commonly treated UGI entry diagnoses; patients who had an initial diagnosis of refractory duodenal ulcer (n = 28), refractory gastric ulcer (n = 41), reflux esophagitis (n = 23), or hemorrhagic gastritis (n = 63) had favorable clinical outcomes of 71 percent, 58 percent, 61 percent, and 62 percent, respectively. Misoprostol was well tolerated, with the most common adverse experience being mild to moderate diarrhea. It is concluded that in humanitarian clinical trials, misoprostol was frequently associated with symptomatic relief, with improvement in UGI hemorrhage, or with endoscopic improvement in severe UGI disease that had proven refractory to available medical therapy. PMID- 3113247 TI - Beneficial effects of aminohexane diphosphonate in patients with Paget's disease of bone resistant to sodium etidronate. AB - Clinical and biochemical resistance to sodium etidronate therapy is not rare in patients with severe Paget's disease of bone, especially after several courses of treatment. Sixteen patients with Paget's disease of bone and well-documented resistance to sodium etidronate were treated with a new diphosphonate, aminohexane diphosphonate, given orally for three months at a daily dose of 400 mg. These patients comprised a selected population of patients with very active disease, as shown by a mean 20-fold increase of serum alkaline phosphatase levels before aminohexane diphosphonate therapy. Aminohexane diphosphonate induced a striking reduction of serum alkaline phosphatase and urinary hydroxyproline levels sustained for up to 18 months after withdrawal of treatment. Two patients had a relapse 14 to 16 months after treatment, and received a second course of aminohexane diphosphonate with the same efficacy. This was accompanied by marked clinical improvement, a reduction of the radioisotope uptake by pagetic bones, and radiologic healing of osteolytic lesions in some cases. Iliac crest biopsy specimens taken after tetracycline double-labeling showed no impairment of bone mineralization. No clinical or biochemical adverse effects have been observed. PMID- 3113248 TI - Aldose reductase inhibitors and diabetic complications. PMID- 3113250 TI - Fetal growth retardation as a complication of pregnancy in patients with neurofibromatosis. AB - Neurofibromatosis adversely affects reproductive performance. Fetal growth retardation as a complication of pregnancy in patients with neurofibromatosis had not been widely documented. The present cases suggest that pregnant patients with neurofibromatosis may have an increased risk for growth-retarded babies. PMID- 3113249 TI - Modulating actions of estradiol on gonadotropin-releasing hormone-stimulated prolactin secretion in postmenopausal individuals. AB - The temporal aspects of estrogen treatment on serum prolactin concentrations basally and in response to a 10 micrograms intravenous injection of gonadotropin releasing hormone were assessed in eight postmenopausal women. The response of prolactin to gonadotropin-releasing hormone stimulation was compared with that of follicle-stimulating hormone and luteinizing hormone obtained simultaneously. Basal serum prolactin increased significantly (p less than 0.001) in response to estrogen treatment, and a positive correlation was found between the serum concentrations of estradiol and prolactin (r2 = 0.266; p = 0.0011). Gonadotropin releasing hormone induced a significant increase in serum prolactin concentrations, which was greater after 5 to 10 days of estrogen treatment compared with that in the estrogen-depleted state (p = 0.031). No correlation was found between gonadotropin-releasing hormone-stimulated prolactin and luteinizing hormone or follicle-stimulating hormone release. These data demonstrate that estrogen treatment of previously hypoestrogenemic postmenopausal women potentiates gonadotropin-releasing hormone-stimulated prolactin release. Furthermore, our data suggest that the previously described paracrine interaction between the gonadotropins and lactotropes exerted by gonadotropin-releasing hormone does not appear to be mediated via increased gonadotropin release. PMID- 3113251 TI - Treatment of polyhydramnios with prostaglandin synthetase inhibitor (indomethacin). AB - Polyhydramnios, which is caused by an excess of amniotic fluid, was diagnosed uniformly in eight patients by ultrasound examination and clinical symptoms, namely, premature uterine contraction, abdominal pain, and respiratory discomfort that resulted from excessive pressure on the diaphragm. Fetal anomalies incompatible with extrauterine existence were excluded by serum alpha-fetoprotein levels, repeated sonography, amniocentesis, and chromosomal analyses. Patients were treated with 2.2 to 3.0 mg of indomethacin/kg body weight/day. The treatment was started at an average gestational age of 24 +/- 0.5 weeks and continued for 2 to 11 weeks. All patients had significant improvement with a simultaneous reduction in amniotic fluid volume, fundal height, and umbilical perimeter. All patients were delivered satisfactorily at an average of 39 weeks' gestation. The fetuses were within the normal body weight range of 2750 to 3600 gm and showed normal development during the neonatal period of 2 to 6 months. Before delivery without indomethacin, the polyhydramnios reformed. Adverse effects or intolerance to the drug was avoided by either a reduction in the dose or cessation of indomethacin therapy. Our studies suggest that indomethacin therapy is an effective way to manage pregnancy complicated by polyhydramnios. PMID- 3113252 TI - In vivo and in vitro modulation of growth hormone and prolactin of a mixed somatotropic-lactotropic pituitary microadenoma. AB - Both in vivo and in vitro responses of prolactin and growth hormone to stimuli were studied in an acromegalic, amenorrheic woman with a chromophobe adenoma of the pituitary gland. Preoperative testing revealed a prolactin rise after thyrotropin-releasing hormone and chlorpromazine and a decline after L-dopa and bromocriptine administration. During 3.5-hour incubations, cultured tumor cells produced significant increases of growth hormone and prolactin after dibutyryl adenosine 3',5'-cyclic monophosphate stimulation, while bromocriptine inhibited both hormones. PMID- 3113253 TI - Transplacental stimulation of functional and morphologic fetal rabbit lung maturation: effect of thyrotropin-releasing hormone. AB - We investigated the effect of maternally administered thyrotropin-releasing hormone on functional and morphologic fetal lung maturation. Thyrotropin releasing hormone (40 micrograms/kg/day) or the vehicle was injected intravenously into the New Zealand White rabbit does on days 25, 26, and 27 of gestation. On day 27 of pregnancy, the does were killed and the fetuses were delivered. The functional pulmonary maturity was assessed by pressure-volume hysteresis while morphologic maturity was assessed by histologic techniques. Enhanced functional and morphologic fetal lung maturation was noted in animals treated with thyrotropin-releasing hormone when compared with controls. An important role of thyrotropin-releasing hormone in fetal lung maturation is proposed. PMID- 3113254 TI - Cost-effective use of antibiotic prophylaxis for cesarean section. AB - Clinical experience has indicated that the prophylactic use of antibiotics reduces infectious morbidity in patients undergoing cesarean section. Several factors must be considered (for instance, in vivo and in vitro efficacy, patient allergies, side effect profiles, status of host defenses, the total cost of therapy, and the risk of selecting resistant organisms that cause superinfections) before prescribing prophylactic antibiotic drugs for this indication. Moreover, medical-legal consequences associated with potential postpartum infections must be considered in assessing the costs and impact of a prophylactic regimen. Results of comparative antibiotic trials in indigent patients undergoing cesarean section demonstrated differing rates of successful antibiotic prophylaxis: piperacillin, 98%; cefoxitin, 91%; cephalothin and ceftazidime, 82%; cefotaxime, 80%; and ampicillin, 77%. Although the acquisition costs of antibiotics vary greatly, these costs are dwarfed by the substantial cost savings that can be realized by use of broad-spectrum antibiotics, which, in our hands, have resulted in reduced laboratory and pharmacy expenses and decreased hospital stays for both mother and neonate. Controlled studies designed to investigate microbiologic as well as clinical efficacy of antibiotics are indicated. Further refinements in individualizing antibiotic regimens according to patient population should be sought. PMID- 3113255 TI - Detailed phenotypic analysis of B-cell lymphoma using a panel of antibodies reactive in routinely fixed wax-embedded tissue. AB - Sixty-three well characterized B-cell lymphomas, with diagnoses previously established by conventional cryostat immunocytochemistry or limited paraffin immunocytochemistry, were studied. The tumors encompassed most of the Kiel subtypes and included the newly recognized entity, sclerosing mediastinal B-cell lymphoma. by the avidin-biotin peroxidase complex technique, each tumor was stained with a panel of monoclonal and polyclonal antibodies reactive in routinely fixed wax-embedded tissues. The panel included four reagents recognizing probable T-cell and B-cell restricted leukocyte common moieties (UCHL1, MT1, MB1, 4KB5), three antibodies to B-cell-related antigens (KiB3, MB2, LN1), and one to a macrophage-related antigen (Mac411). Other antibodies employed included anti-mu chain, anti-kappa, anti-lambda, and seven antibodies to non phenotype-associated antigens, including HLA-DR (TAL-1B5, LN3, LN2, MB3), CD15 (C3D-1), and CD30 (BER-H2). Monotypic surface or perinuclear space and cytoplasmic immunoglobulin were detected in 80% of cases. Distinctive immunocytochemical profiles were demonstrable in many tumor categories by means of the panel of antibodies, thus facilitating the differential diagnosis of tumors of similar morphology. These results, together with our work on T-cell lymphoma in paraffin sections, show that accurate phenotypic analysis of lymphoma is now possible in routinely processed tissues. PMID- 3113256 TI - Cellular responses to the intradermal injection of recombinant human gamma interferon in lepromatous leprosy patients. AB - The local response to a single intradermal injection of 10 micrograms recombinant gamma-interferon (rIFN gamma) has been studied in 17 patients with lepromatous leprosy. Of these, 2 patients additionally received two intradermal injections of 10 micrograms rIFN gamma at another site. The results were compared with those of 3 patients who received three injections of the same dose at a single site in an earlier study. One to 7 days after lymphokine administration 4-mm punch biopsies were obtained and examined for cellular alterations in the dermis and epidermis. This allowed a kinetic analysis of mononuclear cell infiltration, keratinocyte proliferation and differentiation, and Langerhans cell redistribution. At 24 hours, the migration of large numbers of helper T cells and monocytes was already prominent and associated with induration. Mononuclear cell accumulation peaked at 72 hours but then persisted for 5-7 days. Only small numbers (one-third or less of total T cells) of suppressor/cytotoxic T cells were present at any time, and granulocytes were absent. Two daily injections of rIFN gamma led to a more intense accumulation of cells. Ten micrograms of rIFN gamma resulted in enhanced keratinocyte proliferation, Ia expression, and thickening of the epidermis. At 24 48 hours major histocompatibility Class II (Ia) antigen was first noted on the dividing cells of the basal layer. By 72-96 hours the entire epidermis exhibited strong expression of Ia antigen on cell surfaces. Repeated doses of lymphokine accentuated these changes and resulted in a more prompt keratinization and sloughing of this layer. Whereas a single dose of rIFN gamma resulted in the upward movement of T6+ Langerhans cells (LCs) in the epidermis, two injections led to a 50% reduction in their numbers and three doses were associated with an almost total loss of detectable T6+ LCs from the epidermis. These are probably sloughed along with keratinocytes. In contrast to the situation with a delayed immune response in the skin (purified protein derivative), no LCs accumulated in the dermis in association with helper T cells. PMID- 3113258 TI - Evolution of P3 morphology in Australopithecus afarensis. AB - The Australopithecus afarensis dental sample exhibits a wide range of variation, which is most notable in the morphology of the lower third premolar (P3). P3 morphology in the A. afarensis sample ranges from the primitive sectorial extreme in AL 128-23 to the derived, bicuspid (molarized) extreme in AL 333w-1. In this paper, the degree and patterning of variation of the 20 known A. afarensis P3s are examined and the evolutionary implications are discussed. Initially, a series of dental and mandibular metric criteria are evaluated to determine whether this sample may be analyzed as a single species. From the metrics, it is clear that the single species hypothesis cannot be rejected. Next, a series of morphological criteria is devised to measure P3 molarization. Taken as a whole, the A. afarensis P3 sample displays more variation than a sample of modern hominoids (Pan troglodytes) and shows a slight trend toward increased molarization through time. When separated by sex, the A. afarensis sample still displays greater variation than the chimpanzee sample; however, only the male A. afarensis specimens show a trend toward increased molarization. Additionally, the male A. afarensis P3s are more molarized than the female, a pattern that is seen as well (though less markedly) in the chimpanzee sample. The trend toward increased molarization over time indicates selection for grinding in A. afarensis. The sexual differences parallel those seen in the postcrania (cf. Stern and Susman: Am. J. Phys. Anthropol. 60:279-318, 1983), as the females tend to retain the primitive condition, while the males display the derived morphology. Consequently, a model of sexual differences in niche exploitation, with the females exploiting a more arboreal environment, would seem to be supported by both the dental and postcranial evidence. PMID- 3113259 TI - Vitamin C biosynthesis in prosimians: evidence for the anthropoid affinity of Tarsius. AB - This report examines the taxonomic distribution of the in vitro biosynthesis of ascorbic acid in the Prosimii (Order: Primates). Liver and kidney samples of 15 prosimian taxa, including Tarsius bancanus, were quantitatively tested for the enzyme L-gulono-1,4-lactone oxidase. Liver samples from all taxa except Tarsius had substantial levels of the enzyme. Furthermore, unlike other eutherian mammals, kidney tissue from members of the family Lemuridae showed low but consistent levels of enzyme activity. The result for Tarsius, by fitting with the pattern exhibited by the monkeys, apes, and man, adds significant independent evidence for this animal's relatively close genetic relationship with the Anthropoidea. PMID- 3113260 TI - Rates of evolution: is there a conflict between neo-darwinian evolutionary theory and the fossil record? AB - Neo-darwinian and population genetics theory assumes that the necessary and sufficient set of conditions for all genetic, therefore evolutionary, change has been identified. Punctuationalists have assumed the opposite and cite the fossil record as evidence for change too rapid to be explained in neo-darwinian theory. Data is given here to provide estimates of the rate of evolution in hominid fossils, in living populations, and of that rate which would qualify as punctuational in the hominid fossil record. Evolution in living populations is orders of magnitude greater than that found in the fossil record and far greater than necessary to create apparently instantaneous saltations in the fossil record. It is suggested that such saltations may not represent more rapid rates of evolution but, rather, the persistence of evolutionary change in a given direction for a longer than normal period. PMID- 3113261 TI - A new species of Propliopithecus from the Fayum, Egypt. AB - Propliopithecus ankeli is described as a new species of hominoid from the early Oligocene of Egypt. The new species occurs at a stratigraphic level 80 m below quarries yielding P. chirobates and Aegyptopithecus zeuxis. P. ankeli differs from other species of the genus in its large size, relatively robust canines, larger and proportionally broader premolars, and M1 that has as great or greater mesiodistal length than M2. Thus, P. ankeli is characterized by increased relative size and robustness of the antemolar dentition, which contrasts with the pattern observed in the Fayum's other large hominoid, A. zeuxis. P. ankeli probably represents a lineage not ancestral to other Fayum hominoids. Discovery of this new species emphasizes the diversity of anthropoid primates that had already evolved by the early Oligocene. PMID- 3113262 TI - Morphometrics and niche metrics in prosimian locomotion: an approach to measuring locomotion, habitat, and diet. AB - Locomotor morphology, it is recognized, cannot be understood without an understanding of locomotor behavior. The interaction of locomotor anatomy and behavior has been successfully analyzed for single species and species pairs. Broader generalizations, however, require the demonstration of anatomical/behavioral associations for numerous sets of species. To accomplish this it is necessary to develop a method for the simultaneous quantitative description and comparison of many different parameters of the locomotor niche: locomotor behaviors, habitat usages, and diets. As a start towards achieving this we present a multidimensional approach to the description of functional parameters of the niche for prosimians. We derive quantitative evaluations of locomotor activity, habitat utilization, and diet for each of 27 species, using field data, film and video records, and the available literature. These parameters are then displayed graphically and clustered to provide profiles for comparisons both of species and variables. The multidimensional profiles reveal valuable information about activity, environment and diet, and their interactions. They permit closer comparisons with equivalent multidimensional information about prosimian structure, based on morphometric studies. The method gives useful graphical and statistical techniques for interspecific comparisons of morphometrics and niche metrics. PMID- 3113257 TI - Assessing the autopsy. AB - This study outlines the role of autopsies in medical practice and health policy, details the nature and reason for declining rates, including those in Rochester, Minnesota, and suggests possible remedial measures to halt or reverse this trend. It is concluded that one of the principal impediments to reversing the declining rate of autopsies is what is referred to in Economics as "market failure." In particular, the nature of the spatial and temporal distribution of costs and benefits has precluded the existence of an incentive structure which can lead to a realization of the major net social benefits from the autopsy. Ultimately, it is only the explicit recognition by the medical profession, government agencies, corporate insurers, and the general public of the nature and significance of this market failure and foregone benefits which can lead to remediation. PMID- 3113263 TI - Relationship between the mandibular condyle and the occlusal plane during hominid evolution: some of its effects on jaw mechanics. AB - A selection of mandibles from recent higher primates, fossil hominids, and hominoids has been studied from photographs of skulls, reproductions, and material published by others, all viewed in the sagittal plane. Tracings of each mandible were constructed so that the dentitions were all scaled to the same length (d) and superimposed. The (scaled) positions of the articular surfaces of the condyles (J = joint point) were compared. The height of each J point above the scaled dentition (h = effective condyle height) and its distance behind the dentition (r = effective ramus width) were compared. With very few exceptions d greater than r greater than d/2. There was a poor correlation between r and the amount of prognathism. The position of the J point with respect to the occlusal plane was different for different groups within the material analysed and could prove to be a useful tool to help improve the reconstruction of fragmented fossil material. Some examples are given. A. afarensis and Homo habilis shared a low and anterior J point (r approximately d/2). The later australopithecines evolved a high and anterior J point, whereas that of Homo erectus was raised and displaced posteriorly (r approximately 3d/4). The value of r was increased to d in the Neanderthals, and recent man has moved the J point forward again. The effect of the position of the J point, the slope of the preglenoid plane, and the curve of Spee on the relationship between upper and lower postcanines when the jaw is opened and then closed to process food have been analysed. The results show that the position of the J point affects the way in which the mandible moves, and this may be related to changes in diet during evolution. PMID- 3113264 TI - Kebara 2 Neanderthal pelvis: first look at a complete inlet. AB - The renewed excavations at the Kebara Cave revealed a Neanderthal skeleton dated at about 50-55,000 years B.P. The pelvis of this individual is the most intact Neanderthal pelvis yet discovered, presenting for the first time a complete inlet. Although the superior pubic ramus is extremely long, as typically seen in the Neanderthals, the size of the pelvic inlet is comparable to that of modern Homo sapiens. The length of the superior pubic ramus is found to stem from a more externally rotated innominate bone and not, as generally assumed, from the larger pelvic inlet. It is suggested that the uniqueness of the Neanderthal pelvis may be attributable to locomotion and posture-related biomechanics rather than to obstetric requirements. PMID- 3113265 TI - Nut-like oil seeds: food for monkeys, chimpanzees, humans, and probably ape-men. AB - The hypothetical hyperrobust australopithecine gnathic nutcracker adaptation is reexamined in light of ecobotanical information on edible wild nuts provided by the flora of tropical and subtropical Africa. The nut producing species are tree forms. Those of the forest region do not as a rule produce fruits with edible mesocarps. In contrast, the woodland savanna species (particularly in the Zambezian region) characteristically provide an important whole fruit, i.e., a nutritious mesocarp in addition to edible oil-rich nut seeds. These fruits drop from the tree before they are fully mature and go through the final ripening phase on the ground. They are important seasonal foods for a variety of vertebrates, including primates, elephants, and antelope. Altogether the nuts exhibit a broad range of toughness values, measured here as strength under compression. The woodland nuts are not as tough (177-934 kg force, breaking load) as those of the tropical forest (192-1,673 kg force). The seed-predators of the woodland species include squirrels, baboons, warthogs, and parrots. Paleoecological analyses indicate that it was the woodland nuts that were probably available to Australopithecus boisei and A. robustus. Preliminary estimates of adult male gnathic nut-cracking capabilities suggest that A. boisei could have orally cracked a significant portion of the woodland nuts. In spite of this, ecobotanical data indicate that we can probably reject the hypothesis that these hominids were year-round gnathic nut-cracking specialists. Both the indirect and direct evidence support this conclusion. PMID- 3113266 TI - Some blood genetic characteristics of several Sudanese tribes. AB - The distribution of ABO and Rhesus blood groups, serum haptoglobin, and transferrin; red cell glucose-6-phosphate dehydrogenase and acid phosphatase; and hemoglobin was studied among the two aboriginal negroid tribes (Nuba and Fur); the Nilotic tribe; five tribes of Arab ancestory; and a mixed group of other minor tribes of Arab origin. The Nilotic and Nuba tribes were genetically quite distinct from the rest, with lower R1, R2, and r in the Rhesus system and low HbS and Gd-. The Arab tribes had a genetic structure which was intermediate between that of the original negroid population of the Sudan and the Arabs to the north. However, some of the Arab tribes had special genetical characteristics, e.g., Messeria had high TfD1; both Messeria and Hawazma had high HbS and Gd-, while GdA was higher only in the Hawazma. The Gaalin had very low HbS, Ro, GdA, and Gd-, suggestive of less negroid admixture compared to Messeria and Hawazma. The Fur, though an aboriginal negroid tribe, had genetic characteristics similar to Arabs. PMID- 3113267 TI - Energy expenditure after infusion of glucose-based total parenteral nutrition. AB - Resting energy expenditure (REE), carbohydrate balance, and lipogenesis were calculated after administration of glucose-based total parenteral nutrition (TPN) to determine whether the thermic effect of glucose is equal to the energy cost of storing the glucose. Estimated cost of storage as glycogen (5.3%) and fat (19%) was compared with measured increases in REE. Patients with malnutrition received 5% dextrose in water and 6 days of TPN with a low (1.2 times REE, group 1) or high (2.0 times REE, group 2) level of glucose intake. Increases in REE by day 6 were 10% (group 1) and 28% (group 2). The theoretical cost of glucose storage as glycogen and fat accounted for approximately 40% of the measured increase in REE in patients in group 2. The thermic effect of TPN (derived from patients in group 1) accounted for most of the balance. The majority of the thermic effect of high levels of glucose infused with TPN can be explained on the basis of the thermic effect of TPN and glucose storage. PMID- 3113268 TI - Comparison of glucose and glucose plus lipid as caloric sources in parenterally fed rats. AB - This study investigated the etiology of fat infiltration of the liver during total parenteral nutrition. We measured the content of liver lipids, serum lipids, liver lipogenic enzymes, rates of in vivo fatty acid synthesis, and carcass composition in rats during continuous intravenous (iv) and intragastric (ig) feeding of two diets containing either 100% glucose or 75% glucose-25% lipid (20% Intralipid). Two groups of orally (O) fed rats were given solid diets similar to either the glucose or glucose-lipid solution in energy and nitrogen content. All six groups of rats (285-295 g) received 230 kcal X kg-1 X day -1 and 766 mg N X kg-1 X day-1. Total liver fat was greater after feeding the glucose diet ig rather than iv. However, feeding the glucose-lipid diet ig but not iv reduced the accumulation of liver fat by 49%. There were no differences in serum glucose concentrations among the three groups fed the glucose solution. Serum glucose concentrations in iv and O rats fed either diet were not significantly different; whereas feeding the glucose-lipid solution ig lowered serum glucose compared with the 100% glucose solution. Insulin concentrations were similar among all groups. The concentrations of serum triglycerides and cholesterol were higher in the groups fed the glucose-lipid diet. The activities of the liver lipogenic enzymes and rates of fatty acid synthesis were higher in iv- and ig-fed rats receiving the glucose diet compared with the glucose-lipid diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113269 TI - Renal substrate utilization in normal and acidotic rats. AB - Renal arteriovenous (A-V) concentration differences of the major potential respiratory substrates were measured in whole blood of control, NH4Cl-acidotic and diabetic ketoacidotic (DKA) rats. Net renal substrate extractions were calculated from A-V differences and renal blood flows. In fed control rats lactate accounted for 78% of the total substrate extracted. Small amounts (10 12%) of citrate and the ketone bodies 3-hydroxybutyrate and acetoacetate were also extracted. There was no significant extraction of either free fatty acids, glucose, glutamine, or pyruvate. In NH4Cl-acidotic rats lactate extraction was lower (40%) than in controls, but glutamine extraction increased (28%). The amount of extra glutamine extracted approximated the fall in lactate extraction. In DKA rats, ketone bodies accounted for the major portion of the extracted substrates (56%) but a significant part of the net extraction was due to urinary excretion of these compounds. Glutamine extraction represented 23% of the total. Lactate extraction was low (14%) in DKA rats, probably as a result of the low arterial lactate concentration. In vitro studies done on renal cortical slices suggest that each of the three major substrates extracted by the kidneys of normal, NH4Cl, and DKA rats could serve as major respiratory fuels. PMID- 3113270 TI - Patterns of reproductive hormone secretion in hibernating Turkish hamsters. AB - Changes in gonadal state and in circulating reproductive hormones [follicle stimulating hormone (FSH), prolactin (PRL), and testosterone] were studied for 30 wk in male Turkish hamsters (Mesocricetus brandti) induced to hibernate by exposure to a short-day, cold environment [10:14-h light-dark (LD) cycle, 6 +/- 1 degree C]. Similar measures were compared in hamsters maintained under short-day warm conditions (10:14-h LD, 21 +/- 2 degrees C). A decrease in testicular size and in hormone levels was observed after 9-12 wk of short-day exposure in all animals. After 24 wk, hormone levels rose again, accompanied by testicular recrudescence, in short-day warm hamsters and in hamsters that failed to hibernate in the cold. For animals that hibernated the temporal pattern of endocrine and gonadal changes differed only slightly in comparison. Testicular recrudescence of hibernators lagged approximately 3 wk behind that of short-day warm hamsters. Hormone levels were generally lower in hibernators sampled during bouts of torpor than during bouts of spontaneous arousal from torpor. A marked elevation of serum FSH was observed in aroused hibernators well before the end of the hibernation season (at 21 wk of short-day exposure). Mean testosterone and PRL values had increased by wk 27, after hibernation was terminated in the majority of animals. These results indicate that testosterone may not be essential for the termination of the hibernation season. The data also suggest that an endogenous timing mechanism, resistant to the decreased body temperature experienced during torpor, may function to trigger a resurgence of the neuroendocrine-gonadal axis at the end of the winter season. PMID- 3113271 TI - Effects of photoperiod on hibernation in castrated Turkish hamsters. AB - Hibernation and circulating reproductive hormones [luteinizing hormone, follicle stimulating hormone, and prolactin (LH, FSH, and PRL)] were studied for greater than 40 wk in castrated male Turkish hamsters (Mesocricetus brandti) housed in either a long-day cold or short-day cold environment. A significantly greater percentage of short-day animals hibernated than did long-day animals, indicating that short-day exposure can predispose Turkish hamsters to enter hibernation and that this photoperiodic effect cannot be explained entirely by the inhibitory influence of short days on testicular endocrine activity. Long-day castrates showed no significant changes in LH or FSH levels during the experiment. In the short-day castrates serum LH, FSH, and PRL levels were reduced after 4-9 wk and increased again after 18-23 wk of short-day exposure. The hibernation season ended after 30-34 wk on short days, several weeks later than in testis-intact males studied previously. These results indicate that gonadal factors are not required for the termination of hibernation but may influence its timing. The resumption of FSH secretion occurred no later during short-day exposure in castrated hibernators than in the preceding study of testis-intact, short-day males hibernating in the cold or those held at room temperature. Thus the endogenous timing mechanism regulating the reactivation of the hypothalamopituitary axis toward the end of the winter season is apparently gonad independent and is little affected by the low body temperatures experienced during hibernation. PMID- 3113272 TI - Adjusted hospital death rates: a potential screen for quality of medical care. AB - Increased economic pressure on hospitals has accelerated the need to develop a screening tool for identifying hospitals that potentially provide poor quality care. Based upon data from 93 hospitals and 205,000 admissions, we used a multiple regression model to adjust the hospitals crude death rate. The adjustment process used age, origin of patient from the emergency department or nursing home, and a hospital case mix index based on DRGs (diagnostic related groups). Before adjustment, hospital death rates ranged from 0.3 to 5.8 per 100 admissions. After adjustment, hospital death ratios ranged from 0.36 to 1.36 per 100 (actual death rate divided by predicted death rate). Eleven hospitals (12 per cent) were identified where the actual death rate exceeded the predicted death rate by more than two standard deviations. In nine hospitals (10 per cent), the predicted death rate exceeded the actual death rate by a similar statistical margin. The 11 hospitals with higher than predicted death rates may provide inadequate quality of care or have uniquely ill patient populations. The adjusted death rate model needs to be validated and generalized before it can be used routinely to screen hospitals. However, the remaining large differences in observed versus predicted death rates lead us to believe that important differences in hospital performance may exist. PMID- 3113273 TI - The economic costs of Alzheimer's disease. AB - This paper estimates the economic costs of Alzheimer's Disease to individuals and to society, based on review of published Alzheimer's Disease-related research. The analysis is derived from epidemiological projections and cost information for the United States population in 1983. Estimated costs include both direct medical care and social support costs, as well as indirect costs, such as support services provided by family or volunteers, and the value of lost economic productivity in Alzheimer's Disease patients. Mid-range estimates of net annual expected costs for an Alzheimer's Disease patient, excluding the value of lost productivity, are $18,517 in the first year and $17,643 in subsequent years, with direct medical and social services comprising about half of these costs. Under base case assumptions, the total cost of disease per patient in 1983, was $48,544 to $493,277, depending upon patient's age at disease onset. The estimated present value of total net costs to society for all persons first diagnosed with Alzheimer's Disease in 1983 was $27.9-31.2 billion. Development of a public or private insurance market for the economic burdens of Alzheimer's Disease would fill some of the gaps in the current US system of financing long-term chronic disease care. PMID- 3113274 TI - Incidence of injuries in high school track and field athletes and its relation to performance ability. AB - Two hundred fifty-seven high school track athletes from 17 teams were observed prospectively for one complete season (77 days) to study the incidence and types of injuries and to establish the relationship among injuries, duration of training, and individual performance ability. One hundred seventy-four (68%) of the athletes were male and 83 (33%) were female. A total of 41 injuries was observed over this period of time. One injury occurred for every 5.8 males and every 7.5 females. On the average, an injury resulted in 8.1 days of missed practice, 8.7 days for males and 6.6 days for females. Sprinting events were responsible for 46% of all injuries. The majority (83%) of injuries involved the lower extremities. Management of these injuries varied greatly. A direct correlation was noted between performance level of the athlete and incidence of injuries. The average noninjured athlete ranked at the 57.4 percentile based on best seasonal performance while the average injured athlete ranked at the 75.4 percentile. This direct relationship was present for both sexes and within all events, although some variation was noted within these separate groups. PMID- 3113275 TI - [Criteria of judging therapeutic efficacy in cerebral ischemia]. PMID- 3113276 TI - [Action of intravenous nitroglycerine on cerebral vascularization]. PMID- 3113277 TI - Long-term treatment needs of hospitalized adolescents. PMID- 3113278 TI - [Thyroliberin test in patients with the climacteric syndrome]. PMID- 3113279 TI - [Treatment of women with trichomonal and bacterial colpitis with the Solco Trichovac vaccine]. PMID- 3113280 TI - Double-blind comparison of the protective effect of sodium cromoglycate and ketotifen on exercise-induced asthma in adults. AB - In a double-blind double-placebo study 10 asthmatics exercised on a treadmill after treatment for 1 week with placebo, or ketotifen 1 mg twice daily, or SCG 10 mg four times daily. The post-exercise percentage fall in FEV1 after SCG but not after ketotifen was significantly smaller than after placebo. A 1-week treatment with SCG but not ketotifen protected against EIA. PMID- 3113281 TI - An unexpected reaction towards disodium cromoglycate. AB - In recent years disodium cromoglycate has become a useful tool in handling allergic rhinoconjunctivitis and asthma. Very few side effects have been reported, and the drug's working mechanism is thought to be its "mast cell stabilizing" effect. A patient with an immediate type I reaction to DSCG is reported on. PMID- 3113282 TI - Should air-oxygen replace nitrous oxide-oxygen in general anaesthesia? AB - The use of compressed air-oxygen mixtures to replace nitrous oxide-oxygen in general anaesthesia was investigated in 378 patients. There were neither prolongations of recovery time nor instances of awareness under anaesthesia. The cost of general anaesthesia using compressed air-oxygen was about half that for nitrous oxide-oxygen mixtures. PMID- 3113283 TI - Atriobronchial fistula: an unusual complication of intravenous feeding in the presence of a mediastinal abscess. PMID- 3113284 TI - Effect of particle size of activated charcoal on separation of Triton X-100 from protein, liver cytosol, and lipoxygenase extracts. AB - Triton X-100 was almost completely removed from bovine serum albumin solutions, BALB/c mouse liver extracts, and avocado peel lipoxygenase extracts by stirring the samples for 30 min in the presence of 250-350 mesh activated charcoal. The procedure did not remove protein significantly and did not reduce enzyme activity. At higher charcoal particle sizes, the efficiency of Triton adsorption was decreased and protein adsorption was increased. ElevateD temperatures enhanced Triton and protein adsorption. Adsorption on activated charcoal of 250 350 mesh is a simple and rapid procedure for Triton removal at a ratio of 0.23 g Triton X-100 per gram of activated charcoal. PMID- 3113285 TI - Simultaneous electrochemical determination of diffusion and partition coefficients of potassium ferrocyanide for albumin-glutaraldehyde membranes. PMID- 3113286 TI - Different antigen expression on Wolffian and Mullerian cells in rat embryos as detected by monoclonal antibodies. AB - The Wolffian duct and the developing Mullerian duct of 14 and 15 day old rat embryos were examined with the monoclonal antibodies GZ1 and GZ2. These antibodies react with antigens situated in the cell membrane of Wolffian cells; they do not react with Mullerian cells. This different antigen expression confirms the current opinion that these cells are of different types. A cellular contribution from the Wolffian duct to the developing Mullerian duct was not found. PMID- 3113287 TI - Eye development in the normal and Pupoid foetus (pf/pf) mutant mouse. AB - Embryonic development of the mammalian eye has not been studied in such great detail as that of the avian eye, and preliminary observations have suggested that the sequence of events may differ. It is therefore likely that the relative importance of the cell and tissue interactions involved also differs and it would be interesting to compare these two systems. The pupoid foetus mutation in the mouse shows disruption of eye development due to abnormal epidermal properties and so the relative importance of individual events in triggering subsequent development can be studied by seeing what happens when the situation is modified in the mutant. The behaviour of the pupoid foetus epidermal cells in the interactive system of the eye may also help to further characterise the phenotype of the mutation. PMID- 3113288 TI - Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO2. AB - Measurement of 133Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO2 at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBF was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO2 of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption. PMID- 3113289 TI - Effect of spontaneous sighs on arterial oxygenation during isoflurane anesthesia in humans. AB - The presence, frequency, and volume of spontaneous sighs was evaluated in 21 (ASA 1-2) supine patients aged 44 +/- 15.2 (SD) yr, during isoflurane-nitrous oxide anesthesia. Before induction the inspiratory capacity of each patient was determined. After induction of anesthesia and tracheal intubation patients breathed spontaneously except for three manual inflations to each patient's predetermined inspiratory capacity at the beginning and end of surgery. Arterial blood gas tensions were measured before and 5 min after each set of mechanical deep breaths and each hour during surgery, the mean duration of which was 2 +/- 0.09 hr. Spontaneous sighs occurred in 13 of 21 patients. The average frequency was 6 +/- 4 sighs/hr. At FIO2 = 0.5, nonsighing patients had an initial PaO2 of 229 +/- 59 mm Hg and sighers had an initial PaO2 of 162 +/- 57 mm Hg (P less than 0.05). Arterial oxygen did not change in sighing patients during the course of surgery, while in nonsighing patients the PaO2 decreased from the initial value of 229 +/- 60 mm Hg to 170 +/- 63 mm Hg (P less than 0.05). Mechanical deep breaths administered at the end of surgery produced no improvement in oxygenation in either sighers or nonsighers. The presence or absence of sighs did not correlate with PaO2 or PACO2. Though the results suggest that spontaneous sighs in some patients may function to help maintain arterial oxygenation, all patients maintained their PaO2 while breathing spontaneously under general anesthesia in the supine position. PMID- 3113290 TI - Pupillary diameter and ventilatory CO2 sensitivity after epidural morphine and buprenorphine in volunteers. AB - The aim of this study was to correlate pupillary diameter with respiratory depression for 20 hr after epidural administration of morphine or buprenorphine. Pupillary diameter and the ventilatory sensitivity to CO2 were measured in six healthy volunteers at various times (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 20 hr) in two sessions, separated by at least 1 week, at which either epidural morphine, 4 mg, or epidural buprenorphine, 0.15 mg, was administered randomly in a double blind manner. Three of the six volunteers received 0.3 mg buprenorphine epidurally in a third session. Pupillary diameter was measured with a modified Essilor pupillometer. The ventilatory CO2 sensitivity was measured by a modified Read rebreathing technique. The ventilatory parameters measured were mouth occlusion pressure during the first 0.1 sec of inspiration (P0.1), end-tidal CO2 (PETCO2), tidal volume (VT) and respiratory rate (RR). Slopes of the linear regression lines (P0.1/CO2, VT/CO2, VE/CO2, and RR/CO2) and the intercept values of the regression lines and PETCO2 = 7.2 kPa (P0.1:7.2, VT:7.2, VE:7.2, and RR:7.2) were calculated. Pupillary diameter after epidural morphine was smallest at the second hour and had returned to normal after eight hours. After epidural buprenorphine there were two periods of miosis, one at 1-3 hr, the other at 10 hr. With epidural morphine, a statistically significant correlation (P less than 0.05) was found between pupillary diameter and VE/CO2, VE:7.2, P0.1:7.2, and VT:7.2. With epidural buprenorphine 0.15 mg a significant correlation was found between pupillary diameter and VE:7.2 and P0.1:7.2. With epidural buprenorphine 0.3 mg the correlations between pupillary diameter and VE:CO2, VE:7.2, and P0.1:7.2 were significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113291 TI - Epidural butorphanol or morphine for the relief of post-cesarean section pain: ventilatory responses to carbon dioxide. AB - To determine the safety, efficacy, and the ventilatory responses to carbon dioxide (CO2) of epidurally administered butorphanol or morphine, 122 healthy women who underwent cesarean section with epidural anesthesia were studied. Patients were randomly assigned to receive one of four epidural regimens for the relief of postoperative pain: 5 mg morphine (n = 32), 4 mg butorphanol (n = 30), 2 mg butorphanol (n = 29), or 1 mg butorphanol (n = 31). Epidural morphine provided satisfactory analgesia with slow onset and long duration of approximately 21 hr. When butorphanol was administered, analgesia of rapid onset was seen with increasing duration and effectiveness observed with increasing dose; approximately 8 hr when using 4 mg. Sixty-two percent of the patients who received morphine had pruritus. Somnolence was the main side effect encountered in patients who received epidural butorphanol. The ventilatory response to CO2 was depressed after morphine and after 2 and 4 mg butorphanol, but the duration of depression was more prolonged after morphine. It is concluded that epidural butorphanol is effective in providing pain relief after cesarean section with minor side effects. However, patients must be observed closely because of possible respiratory depression. PMID- 3113292 TI - On the methods of obtaining diphyllobothriid surface antigens. AB - A new method of obtaining the diphyllobothriid surface antigens has been developed. It allows to obtain antigens with the increased content of the surface components of worm strobila. It was found that the antigens from extracts I are relatively more active than the antigens from extracts II and III. PMID- 3113294 TI - Study designs in infection control research. Research Committee of the Association for Practitioners in Infection Control. PMID- 3113293 TI - Recapping the accidental needlestick problem. AB - A funnel-shaped shield of 1 to 2 cm diameter at the mouth of a needle cap is shown to be effective at decreasing the number of accidental misses occurring in a recapping trial. An argument is made for recapping needles and incorporating new needle cap designs in a revision of the CDC guideline on needle disposal. PMID- 3113295 TI - A comparison of inhaled albuterol and cromolyn in the prophylaxis of exercise induced bronchospasm. AB - Inhaled albuterol and cromolyn by spinhaler have both been shown to be effective in the treatment of exercise-induced bronchospasm. Eighty subjects with exercise induced bronchospasm participated in a randomized parallel group study comparing albuterol (180 microgram) and cromolyn (20 mg) administered 15 minutes prior to a standardized treadmill challenge. The cromolyn group was restudied after 2 and 4 weeks of 4 times/day cromolyn therapy. The albuterol group was also studied at 2 and 4 weeks, but they only used their inhaler as needed between study visits. The mean maximum FEV1 drop post-exercise in the albuterol group improved from 33% (screening visit) to 6% (treatment day 1). The cromolyn group showed significantly less (P less than .01) improvement than the albuterol group (31% drop at the screening visit to 14% drop at treatment day 1). When 2 or 4 weeks of continuous cromolyn therapy was given in addition to a dosage 15 minutes prior to exercise, there was no significant difference compared with acute cromolyn administration alone. In summary, acute administration of albuterol was better prophylaxis for exercise-induced bronchospasm than acute or chronic cromolyn treatment. PMID- 3113296 TI - IgE complexes in food allergy. AB - We have studied patients with the diagnoses of asthma, eczema, and arthralgia by monitoring the formation of immune complexes containing IgE after antigen egress from the gut before and after challenge with food. Following challenge, immune complexes containing IgE, IgG, and antigen are detectable in the circulation. Their appearance correlates with the production of symptoms. The effect of sodium cromoglycate was to prevent the appearance of complexes. This was associated with absence of symptoms. It is suggested that a local IgE-mediated mechanism acts as a "trigger" for the entry of antigen and the formation of immune complexes by altering the permeability of the gut mucosa. The resulting delayed onset symptoms could be viewed as a form of serum sickness with few or many target organs affected. PMID- 3113298 TI - [Enzymatic reagent for CO2 assay on COBAS: 12 hours stabilization at ambient temperature]. PMID- 3113299 TI - [Anti-activator inhibitors of plasminogen]. AB - Plasminogen Activator Inhibitors (PA Inhibitor) have recently been identified in plasma. They are directed against t-PA and Urokinase. Two PA Inhibitors have been described: PA Inhibitor 1 from endothelial cells, hepatocytes and platelets and PA Inhibitor 2 from placenta. Enzymatic assays have been developed. They show that plasma levels of PA Inhibitor are very low under normal conditions, but a considerable increase (X10 or 20) is found in several pathological conditions (thrombo embolic disease, atherosclerosis, thrombotic risk factors (obesity, hypertriglyceridemia, diabetes) inflammatory syndrome, post operative period for PA Inhibitor 1, and in some physiological conditions (pregnancy for PA Inhibitor 2). These results plead for a pathogenic role of PA Inhibitor 1 in the development of thrombosis. Pharmacological products able to decrease the plasma level of PA Inhibitor are as yet scarce. Stanozolol, an anabolic steroid, some biguanides such as Metformin possess this property. PMID- 3113297 TI - Theophylline: primary or tertiary drug? A brief review. PMID- 3113300 TI - [New thrombolytic agents]. AB - Tissue Plasminogen Activator (t-PA), Single Chain Urokinase Plasminogen Activator or pro-Urokinase (scu-PA or pro-UK) and acyl enzymes are new thrombolytic agents, characterized by a high fibrin affinity, so that they provoke only mild systemic fibrinolytic effect. Their infusion would allie good thrombolytic activity and reduced hemorragic risks, usually related to fibrinogen and others coagulation factors degradation t-PA and scu-PA are natural, physiological substances, obtained by recombinant DNA technology. t-PA infusion in acute myocardial infusion (AMI) has been shown to be at least as efficient than intracoronary Streptokinase (SK) administration, but fibrinogenolysis was much lower as compared to SK. In vitro studies have shown that scu-PA was an efficient thrombolytic agent and has a relative fibrin specificity, at least as similar to t-PA, but much superior to classical Urokinase. The acyl-enzyme APSAC or Eminase is a SK-plasminogen complex in which the proteolytic site has been inactivated with an anisoic-acid. This acyl enzyme has a longer half-life than t-PA and scu PA, and can be injected as a bolus. Its administration in AMI have shown that APSAC is as effective as SK, but can also provoke severe fibrinogenolysis. These 3 agents seem to have similar thrombolytic activities on coronary thrombi. However, further studies are required to evaluate the bleeding incidence and coronary reocclusion rates associated with their utilisation. PMID- 3113301 TI - [The so-called short bowel syndrome in adults]. PMID- 3113302 TI - Serodiagnosis of histoplasmosis and blastomycosis. PMID- 3113303 TI - Comparative oxidative microbicidal activity of human blood monocytes and alveolar macrophages and activation by recombinant gamma interferon. AB - The relative oxidative and microbicidal activities of human blood monocytes compared with those of alveolar macrophages (AM) are poorly defined. Furthermore, the comparative efficiency of recombinant gamma interferon (rIFN gamma) to enhance microbicidal function of these 2 cell populations is uncertain. In this study, blood monocytes and AM were obtained concomitantly from 10 healthy, nonsmoking human subjects. Cells were adjusted to equivalent cell concentrations and assayed for respiratory burst activity (superoxide anion production) during soluble (Concanavalin A) or particulate (bacteria) stimulation. Microbicidal activity against Pseudomonas aeruginosa, Listeria monocytogenes, and Candida albicans was also determined for each cell type. Finally, the capacity of rIFN gamma treatment (200 U/ml for 24 h) to enhance these cellular activities was determined. Oxidative activity of AM was greater than that of blood monocytes (p less than 0.01, bacteria; p less than 0.02, Con A). Likewise, AM exhibited greater killing of P. aeruginosa (p less than 0.01) and L. monocytogenes (p less than 0.01) than did monocytes. Neither cell killed C. albicans. Treatment with rIFN gamma greatly enhanced both respiratory burst and microbicidal activity of blood monocytes, but had no effect on AM respiratory burst. Despite this, rIFN gamma-treated AM did exhibit some enhanced killing of L. monocytogenes (p less than 0.05). We conclude that oxidative microbicidal activity of resident AM greatly exceeds that of blood monocytes, but that blood monocytes are relatively more susceptible to activation by rIFN gamma. PMID- 3113304 TI - Evaluation of enzyme immunoassay as a rapid screening test for histoplasmosis and blastomycosis. AB - This study evaluates the usefulness of enzyme immunoassay (EIA) as a screening test for serum antibodies to Histoplasma capsulatum and Blastomycoses dermatitidis and compares the results using this assay with those using complement fixation (CF), immunodiffusion (ID), and radioimmunoassay (RIA), in 12 patients with active histoplasmosis, 12 with active blastomycosis, 28 with other acute or chronic lung diseases and 25 healthy blood donors from an endemic area; EIA was as sensitive as RIA and more sensitive than CF and ID in the 24 patients with active fungal infections. The specificity of EIA was equal to that of the other serologic tests. We conclude that EIA is a useful screening test for serum antibodies to H. capsulatum and B. dermatitidis that avoids some of the problems associated with other sensitive assays such as RIA. A negative EIA result is evidence against invasive histoplasmosis or blastomycosis and suggests an alternative diagnosis. PMID- 3113305 TI - Ventilation and breathing patterns during hemodialysis-induced carbon dioxide unloading. AB - Important CO2 unloading occurs during hemodialysis (HD) when acetate-buffered dialysate is used. This is accompanied by alveolar hypoventilation. To gain more insight into the mechanisms of this alveolar hypoventilation, breathing patterns were studied in 5 patients with end-stage renal failure during HD using acetate buffered dialysate, which induces CO2 unloading, or bicarbonate without CO2 loss. Ventilation was continuously measured with calibrated respiratory inductance plethysmography using techniques of multiple linear regression analysis. At regular intervals, arterial blood gas was sampled and expired air was analyzed. Breathing patterns were analyzed for VE, VT, TI, TE, and VT/TI. All data were compared with the respective starting value and with the respective value in the other setup. A greater decrease in ventilation was seen during HD with an acetate containing dialysate because of irregular breathing patterns that resulted in a prolongation of expiratory time. Important variations in tidal volumes, striking apnea periods, and occasional periodic breathing were observed. We suggest that these irregularities are due to CO2 unloading leading to the point where ventilation is totally mediated through the output of the peripheral chemoreceptors. PMID- 3113306 TI - Role of membrane lipids in the pulmonary vascular abnormalities caused by bacterial toxins. PMID- 3113307 TI - Oxygen radicals from arachidonate metabolism in abnormal vascular responses. AB - The involvement of oxygen radicals produced in association with arachidonate metabolism via PGH synthase in cerebral vascular responses is reviewed. PGH synthase generates superoxide in the presence of NADH or NADPH. Lipoxygenase also produces superoxide under similar conditions, but it is a much less important quantitative source for this radical. Radicals from the PGH synthase pathway are produced in vivo during topical application of arachidonate or bradykinin, a polypeptide that releases endogenous arachidonate from tissues. The vascular changes in response to arachidonate and bradykinin consist of functional, morphological, and biochemical alterations. Oxygen radicals from this pathway appear to play a role in the cerebral vascular changes in acute, severe hypertension and in fluid percussion brain injury. PMID- 3113308 TI - Obliterative bronchiolitis after heart-lung transplantation: apparent arrest by augmented immunosuppression. AB - Obliterative bronchiolitis has been the major complication in long-term survivors of human heart-lung transplantation at our institution. We have assessed the effect of the introduction of a third immunosuppressive agent, azathioprine, on the rate of decline in airflow variables in eight heart-lung transplant recipients with obliterative bronchiolitis, and have compared this rate with that in five patients who did not receive augmented immunosuppressive therapy. Specifically, the rate of decline in forced expiratory flow rate between 25% and 75% of vital capacity improved considerably after institution of this therapy ( 5.25 +/- 2.85 compared with -0.27 +/- 0.66 [mean +/- SD]; p less than 0.005), whereas the effect on the ratio of forced expiratory volume in one second to forced vital capacity was more modest (-3.61 +/- 1.52 compared with -0.54 +/- 0.93; p less than 0.005). The rate of decline in airflow variables was similar in both groups before the institution of therapy with azathioprine. These results show that augmented immunosuppressive therapy is capable of slowing the rate of progression of obliterative bronchiolitis in this population; they also suggest that the obliterative bronchiolitis may represent a form of chronic pulmonary allograft rejection. PMID- 3113310 TI - Anticardiolipin antibodies and the lupus anticoagulant. PMID- 3113309 TI - Alterations in serum thyroid hormonal indices with colestipol-niacin therapy. AB - A serial blood-lipid-lowering study at the University of Southern California yielded unexpected findings on routine thyroid function monitoring. After 1 year of combined colestipol and niacin therapy, patients had reduced total serum thyroxine (T4) levels and increased triiodothyronine uptake ratios, an indicator of apparent decreases in thyroxine-binding globulin levels. Calculation of the free T4 index partially but not completely corrected for the apparent decrease in thyroxine-binding globulin, as determined by a relatively small decrease in the free T4 index compared with a large decrease in T4. Sequential sampling, using three separate methods, showed reduced thyroxine-binding globulin levels. The mechanism for these changes is unknown, but the fact that these patients were essentially euthyroid needs emphasis because the use of combined colestipol and niacin therapy is becoming more widespread. PMID- 3113311 TI - The role of ascorbate in biomembrane energetics. AB - The mechanism(s) whereby membrane translocations are energized are poorly understood. Our work has focused on transmembrane microsomal and plasma membrane redox constituents as a means to energize membranes via alternative mechanisms complementary to ATP-driven processes. One such component is NADH-ascorbate free radical (mono- or semidehydroascorbate) oxidoreductase. This activity is associated with the trans or exit face of the Golgi apparatus, transport vesicles that move between the Golgi apparatus and the plasma membrane, and with the plasma membrane itself. Various lines of evidence, mostly indirect, link this activity to membrane translocations. Included is an apparent activation of the reductase in membranes when coated with clathrin, a single large polypeptide chain involved in exocytosis and in receptor-mediated and absorptive endocytosis. The results are consistent with a role of the ascorbate free radical as an acceptor for electron transport-mediated transfer of electrons from NADH perhaps to oxygen by coated membranes as a part of a mechanism to drive membrane translocations via generation of a proton gradient or of a membrane potential. Additionally, plasma membrane redox may be important in the regulation of cell growth, but a strict dependence on ascorbate free radical for the latter seems less likely than with internal endomembranes, where redox function may strictly depend upon the restricted pool of regeneratable acceptor that the ascorbate free radical provides. PMID- 3113312 TI - The role of ascorbic acid in the biosynthesis of the neuroendocrine peptides alpha-MSH and TRH. PMID- 3113313 TI - Evolution of organisms and organelles as studied by comparative computer and biochemical analyses of ribosomal 5S RNA structure. AB - The results documented in this publication demonstrate that for evolutionary studies the ribosomal 5S rRNA is a suitable object for such an investigation and that as many methods as possible should be consulted. In this study the results of biochemical and chemical experiments were combined with those of computer sequence analyses, and they revealed that these methods complement each other nicely. We are currently at a state at which we are able to well define the secondary structures of the 5S rRNAs for eubacteria, organelles, archaebacteria, and eukaryotes and we are even able to propose a secondary structure for a Ur-5S rRNA. It is also clear that in the future the present studies should be continued and extended in such a way that the tertiary structures of these molecules will become known. PMID- 3113314 TI - The origin of eukaryotic and archaebacterial cells. PMID- 3113315 TI - Treatment of superior limbic keratoconjunctivitis with topical cromolyn sodium. AB - Eight patients with superior limbic keratoconjunctivitis (SLKC) were treated with topical cromolyn sodium. All standard modes of therapy had failed. Six patients manifested marked improvement or complete resolution of their condition. The administration of cromolyn sodium appears to be a safe and effective alternative in the treatment of SLKC. PMID- 3113316 TI - Surgical therapy of a Pseudomonas corneal ulcer in a diabetic. AB - A 30-year-old white woman with diabetes was seen with a Pseudomonas corneal ulcer. The ulcer progressed despite appropriate antibiotics, and the patient was treated with surgical debridement. Pseudomonas infections in a compromised host are discussed. PMID- 3113317 TI - The lactoferrin test for the diagnosis of keratoconjunctivitis sicca in clinical practice. AB - Tear fluid lysozyme concentration, measured by means of the agar diffusion assay, and lactoferrin concentration, measured with radial immunodiffusion using the Lactoplate test, were determined in 112 persons in routine clinical practice. About one third of these persons had symptoms and signs compatible with keratoconjunctivitis sicca. A good correlation was found between these tear proteins in the tear fluid in persons with normal tear function and in those with a tear function disorder. In 8%, false-positive and false-negative results were obtained, but the difference in associated values of lysozyme and lactoferrin concentration was small. PMID- 3113318 TI - Ocular coloboma associated with a solitary maxillary central incisor and growth failure: manifestations of holoprosencephaly. AB - A one-year-old boy presented with findings of ocular colobomas and staphylomas in both eyes. He also had a single central incisor and growth failure. His mother had hyposmia. We think that the patient and his mother represent the mild end of the spectrum of autosomal dominant holoprosencephaly. PMID- 3113319 TI - [Treatment of postoperative pain in gynecologic surgery using 3 non-steroidal anti-inflammatory drugs]. PMID- 3113320 TI - [Laryngeal involvement in von Recklinghausen's disease]. PMID- 3113321 TI - [Synergic effect of GABA and glycine in the antagonism of convulsions caused by pentetrazole in rats. Study of glycine valproamide]. PMID- 3113322 TI - Gonadal vein sampling in patients with idiopathic varicoceles. A preliminary communication. PMID- 3113324 TI - Pre- and postnatal development of adipose tissue at four sites in the guinea pig: effect of maternal diet restriction during the second half of pregnancy. AB - The effect of maternal diet restriction on the subsequent development of four adipose tissue depots has been studied in the guinea pig. Fetuses taken from, and pups born to, pregnant sows fed ad libitum (AL) displayed an increase in fat pad mass and in fat cell mass with increasing body mass at the four selected depots (interscapular (IS), retroperitoneal (RP), groin side subcutaneous (GS) and behind arm subcutaneous (BA)). The effect of maternal diet restriction (50% AL rations during the second half of pregnancy) was to significantly reduce the body masses at birth of the pups. The masses of the BA and GS fat pads and the mass of fat cells in the depots were reduced accordingly. However, the fat depot masses and fat cell masses of the IS and RP fat pads were larger than those of pups of comparable body mass born to AL fed sows. Diet restriction during the second half of pregnancy exerted preferential 'sparing' effects on the 'thermogenic' adipose tissue depots (IS and RP) suggesting the possibility that 'thermogenic' adipose tissue is more likely to be 'programmed' earlier in pregnancy than 'storage adipose tissue' (BA and GS). PMID- 3113323 TI - [Gastroduodenal ulcer pathology and prostaglandins]. PMID- 3113325 TI - Ascorbic acid requirement and assessment of ascorbate status in the common marmoset (Callithrix jacchus). AB - Marmosets can tolerate an ascorbic acid (AA) deficiency for several weeks without clinical symptoms. After being fed an AA-free diet for 3 months, nonspecific deficiency symptoms became obvious. Different dietary levels of AA resulted in corresponding serum ascorbate levels. The kidney threshold of AA in marmosets is comparable to that in humans. When the minimal AA requirement is defined as the amount that is necessary to maintain a serum AA level above the kidney threshold, then about 20 mg AA/kg body weight is needed. This intake was achieved in our trial with a diet containing 500 ppm AA. Thus, the AA requirement of marmosets is severalfold higher than the AA requirement of humans. PMID- 3113326 TI - Impact of virus infection on host cell protein synthesis. AB - There is good evidence that a variety of viruses encode functions that inhibit activation of either ribonuclease L or the Pl/eIF-2 alpha kinase. In general, this capability is evident among viruses that maintain long-term active or latent infections, and must therefore deal with interferon-induced antiviral responses of their hosts. PMID- 3113327 TI - G proteins: transducers of receptor-generated signals. PMID- 3113328 TI - Prevalence of macrolides-lincosamides-streptogramin B resistance and erm gene classes among clinical strains of staphylococci and streptococci. AB - A total of 332 staphylococcal and 263 streptococcal isolates from three hospital microbiology laboratories were tested with erythromycin, clindamycin, and vernamycin B alpha to determine the prevalence of macrolides-lincosamides streptogramin B resistance. Constitutive resistance was detected in 28 Staphylococcus aureus isolates (15.5%), 53 coagulase-negative staphylococci (35.1%), and 20 streptococci (7.6%). Inducible resistance was observed in 13 S. aureus isolates (7.2%), 25 coagulase-negative staphylococci (16.6%), and 2 streptococci (0.8%). Eleven coagulase-negative staphylococci (7.3%) exhibited a novel phenotype, namely inducible resistance to erythromycin and vernamycin B alpha but not clindamycin. Among the staphylococci, two variants of the inducible phenotype detected with the agar diffusion assay correlated with the presence of classical ermA or ermC genes, respectively, by dot-blot analysis. The prevalence of the staphylococcal phenotypes were different in the hospitals surveyed, and there was an apparent inverse correlation between the resistance observed and the use of erythromycin in each hospital. PMID- 3113329 TI - Randomized, single-blind evaluation of cefadroxil and phenoxymethyl penicillin in the treatment of streptococcal pharyngitis. AB - A total of 150 children from two pediatric practices with clinical and bacteriologic evidence of acute group A beta-hemolytic streptococcal (GABHS) pharyngitis randomly received cefadroxil monohydrate (75 children) or phenoxymethyl penicillin (75 children). Cefadroxil was given once daily, while penicillin was given three times daily. The treatment groups were similar in age, sex, race, illness severity, and acute GABHS symptomatology. Throat cultures were routine 3 to 5 days after the start of therapy and 2 and 14 days after the end of therapy. The bacterial cure rates were 90% (62 of 69) for cefadroxil-treated patients and 76% (52 of 68) for penicillin-treated patients. This difference was significant (P less than 0.04). The clinical response was satisfactory in 91% of cefadroxil-treated patients and 89% of penicillin-treated patients. We conclude that once-daily cefadroxil is at least as effective as three-times-daily penicillin in producing bacteriologic eradication and clinical symptomatic improvement in children with GABHS pharyngitis. PMID- 3113330 TI - Ciprofloxacin interactions with imipenem and amikacin against multiresistant Pseudomonas aeruginosa. AB - In vitro interactions of ciprofloxacin with imipenem and amikacin were evaluated by the killing-curve technique against 26 Pseudomonas aeruginosa strains resistant to amikacin and resistant or moderately susceptible to ciprofloxacin and imipenem. Imipenem enhanced killing by ciprofloxacin in tests with 11 strains, whereas amikacin enhanced killing in tests with only 4 strains. PMID- 3113331 TI - Effect of ciprofloxacin on carrier rate of Neisseria meningitidis in army recruits in Finland. AB - The efficacy of ciprofloxacin in eradicating pharyngeal colonization of Neisseria meningitidis was studied among army recruits in Finland. Ciprofloxacin (250 mg) or placebo was given twice a day for 2 days to 118 meningococcal carriers. Meningococcal carriage was eradicated in 96% of subjects given ciprofloxacin and in 13% of those given placebos. PMID- 3113332 TI - A novel immunoassay system and bioseparation process based on thermal phase separating polymers. AB - Poly-N-isopropylacrylamide (polyNIPAAm), a water-soluble, thermally precipitating synthetic polymer, has been conjugated together with a monoclonal antibody (MAb) and utilized in a novel separation method for an immunoassay. The PolyNIPAAm precipitates out of water above a critical temperature of 31 degres C, enabling a polymer-bound immune complex to be separated from the solution. The principal advantages of this method are that it utilizes a homogeneous incubation for the antigen-antibody reaction, plus, it has the ability to assay large-molecular weight antigens with sensitivities equivalent to other nonisotopic heterogeneous immunoassays. In addition, since the polymer-immune complex may be reversibly redissolved by cooling, the method may be used both to concentrate the signal and isolate the analyte. This general technique may also be used for a wide variety of separation processes in addition to immunoassays, in which a specific component in a biological fluid, industrial process stream, or body of water is to be isolated for analysis, recovery, or disposal. Thus, product recovery and/or toxin or pollutant removal processes are possible with this methodology. PMID- 3113333 TI - Differential expression and function of three closely related phenobarbital inducible cytochrome P-450 isozymes in untreated rat liver. AB - The levels of expression of cytochromes P-450b and P-450e (both inducible by phenobarbital (PB) and differing by only 14 of 491 amino acids) in liver microsomes from untreated male rats were separately quantitated by Western blotting with a polyclonal antibody raised against P-450b that is equally effective against P-450e (anti P-450b/e). A protein with mobility identical to P 450e was detected in all microsomal samples. Microsomes from uninduced livers of individual male rats from five different strains exhibited only minor interstrain and interindividual variability in the expression of P-450e (17 +/- 5 pmol P 450e/mg microsomal protein) with the exception of the Brown Norway strain (8.5 +/ 0.5 pmol P-450e/mg). Expression of P-450b varied widely from undetectable levels (less than 2 pmol/mg) in most Sprague-Dawley rats to about 50% of P-450e levels in Fischer and Brown Norway strains. Anti P-450b/e inhibited total metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) by uninduced microsomes, to an extent dependent on rat strain (15-30%), predominantly through inhibition of formation of 12-hydroxymethyl-7-methyl BA (12HOMMBA) (65-85%), the major metabolite of purified P-450e. A specific activity for P-450e-dependent DMBA metabolism was calculated from four sets of microsomes where the P-450b content was either undetectable or very low (0.7-1.0 nmol/nmol P-450e/min-1). Comparable calculated activities were, however, obtained from other untreated rat liver microsomes where P-450b levels were significant. Polymorphism in P-450b was detected but did not affect total P-450b expression or the sensitivity of DMBA metabolism to anti P-450b/e. A fourth band of greater mobility than P-450b (apparent Mr less than 50,000), was also recognized by anti P-450b/e. The intensity of this band did not vary among individual rats or among the different strains and therefore did not correlate with the sensitivity of microsomal DMBA metabolism to anti P-450b/e. A monoclonal antibody (MAb) against P-450b (2-66-3) recognized P-450's b, b2, and e on Western blots but did not react with this higher mobility band. MAb 2-66-3 and two other MAbs produced against P-450b inhibited 12-methylhydroxylation of DMBA by untreated rat liver microsomes to the same extent as anti P-450b/e. Following PB induction, P-450b was induced to about double the level of P-450e in most rat strains examined.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3113335 TI - Radical driven Fenton reactions--evidence from paraquat radical studies for production of tetravalent iron in the presence and absence of ethylenediaminetetraacetic acid. AB - Micromolar concentrations of nonchelated ferrous sulfate catalyze a reaction between H2O2 and radiolytically generated paraquat radicals, causing the concurrent oxidation of deoxyribose to thiobarbituric acid reactive products. The oxidation yield per paraquat radical increases with increasing concentration of deoxyribose, and decreases as the instantaneous or steady-state concentration of paraquat radicals is increased, thus explaining previous anomalies in which oxidation was not observed at high paraquat radical concentrations. The process is not mediated by OH. (which gives different products) but is attributed to an oxidizing intermediate resulting from the two electron oxidation of Fe2+ to a peroxo complex, or a derivative of tetravalent iron. Similar but less pronounced concentration dependences occur in the corresponding oxidation of formate or of deoxyribose catalyzed by Fe(EDTA), where at pH 7.3 90% of the pathway is attributed to one electron oxidation of the Fe2+(EDTA) by H2O2, producing OH., while two electron oxidation accounts for the remaining 10%. PMID- 3113334 TI - Hormonal effects on mitochondrial respiration: potential role of endogenous lipolytic activities. AB - Hormonal effects on heart mitochondrial metabolism are investigated by comparing respiratory rates, Ca2+ uptake capacity, and lipolytic activities of mitochondria isolated from control rats to those of mitochondria isolated from thyroparathyroidectomized animals. Two biochemically and morphologically distinct populations of heart mitochondria are prepared--one derived from the region of the cell directly beneath the sarcolemma (subsarcolemmal mitochondria), the other originally between the myofibrils (interfibrillar mitochondria). Subsarcolemmal mitochondria isolated from normal rat cardiac tissue have both lower respiratory rates and Ca2+ uptake capacity than do interfibrillar mitochondria. However, when these mitochondrial populations are isolated from hearts from thyroparathyroidectomized rats, there is a selective increase in the maximal ability of the subsarcolemmal mitochondria to accumulate Ca2+, which is accompanied by a proportionate increase in their maximal respiratory rates. Neither Ca2+ uptake capacity nor respiratory rates are similarly increased in the interfibrillar mitochondria. Cytochrome contents and mitochondrial protein recoveries are not significantly changed in either of these mitochondrial preparations. The relationship between these selective increases in respiratory properties of the subsarcolemmal mitochondria to endogenous lipolytic activities is also investigated. It was previously demonstrated that, in the absence of Ca2+, both the rate and extent of formation of free fatty acids from endogenous phospholipids is greater in subsarcolemmal than interfibrillar mitochondria (J. W. Palmer et al. (1981) Arch. Biochem. Biophys. 211, 674-682). In this study it is shown that lipolysis is also more sustained in the subsarcolemmal mitochondria when Ca2+ is added. In the subsarcolemmal mitochondria isolated from thyroparathyroidectomized rats, however, the rates of release of stearic acid and oleic acid are reduced in both the presence and absence of Ca2+. In the presence of added Ca2+, the rate of release of arachidonic acid is also decreased compared to control subsarcolemmal mitochondria, suggesting that the expressed activity of Ca2+-activated phospholipase A2 is lower in those mitochondria isolated from the thyroparathyroidectomized animals, in which respiratory rates and Ca2+ uptake capacity are increased. PMID- 3113336 TI - Effect of acute ethanol on serine biosynthesis in liver. AB - The effect of an acute intraperitoneal dose of ethanol (1 g/kg), glucose (7.2 g/kg), or the combination of the two on the metabolite pattern of the biosynthetic pathway of L-serine has been determined in rabbit liver in vivo as has the effect of 10 mM ethanol on the glucose-, fructose-, or pyruvate stimulated accumulation of L-serine in rabbit hepatocytes in vitro. In vivo, the 50% increase in L-serine and 80% increase in L-phosphoserine content of liver following glucose injection was completely prevented by ethanol. In fact, the L phosphoserine content fell to only 6% of the control value. In spite of these and other significant changes in the metabolite pattern of the pathway of L-serine biosynthesis (D-3-phosphoglycerate dehydrogenase, L-phosphoserine aminotransferase (PSAT), and L-phosphoserine phosphatase), the mass action ratio of the combined reactions of the first two steps remained close to their equilibrium position. As a consequence it is estimated that the tissue content of phosphohydroxypyruvate fell to less than 2% of the control value, to approximately 0.3% of its Km for the PSAT reaction. The conclusion that acute ethanol blocks L-serine biosynthesis (presumably by redox effects) was supported by the prevention or inhibition of L-serine accumulation in hepatocytes metabolizing glucose, fructose, or pyruvate. Because L-serine is an important source of one-carbon fragments, the inhibition of its biosynthesis may be another mechanism by which ethanol interferes with folate and one-carbon metabolism. PMID- 3113337 TI - "Stable" effects of insulin and isoproterenol on adipocyte pyruvate dehydrogenase. AB - Insulin, at a concentration of 1 mU/ml, stimulated glycogen synthase and pyruvate dehydrogenase about threefold in isolated rat adipocytes. Upon the removal of insulin, glycogen synthase activity remained in the activated state for 10 min and thereafter rapidly returned to basal level. On the other hand, insulin stimulated pyruvate dehydrogenase activity remained elevated for at least 30 min. Isoproterenol (10(-8) M) stimulated phosphorylase and inhibited pyruvate dehydrogenase through the activation of beta-adrenergic receptors. Addition of the beta-antagonist, propranolol (10(-5) M), after isoproterenol reversed the action of isoproterenol on phosphorylase but not its action on pyruvate dehydrogenase. Dibutyryl cyclic AMP, when added to intact adipocytes, produced an effect on pyruvate dehydrogenase similar to that induced by isoproterenol. Our results indicate that both insulin and the beta-agonist have a unique action on pyruvate dehydrogenase which is different from their effects on other enzymes such as glycogen synthase and phosphorylase. PMID- 3113338 TI - [Clinical study of intraperitoneal chemotherapeutic perfusion (IPCP) of mitomycin C (MMC) and intraperitoneal administration of cisplatin]. AB - IPCP was performed in an attempt to control ascites production by malignant tumors, and its inhibitory effect on ascites production was studied. The subjects were 24 patients who underwent surgery at this department between April 1981 and April 1986, consisting of 19 cases of ovarian cancer, 3 cases of cancer of the uterine body, 1 case of retroperitoneal tumor, and 1 case of metastatic ovarian cancer. As the treatment at the time of laparotomy, 30 mg of MMC was dissolved in 300 ml of normal saline and intraperitoneally administered. After holding for 30 minutes, it was discharged by cleaning out the abdominal cavity with 3,000 ml of normal saline. Immediately before closure of the wound, (A): MMC 10 mg, OK-432 100 KE, neocarzinostatin 4,000 units, or (B): (A) + cisplatin 100mg, was intraperitoneally injected, and the wound was closed without washing out this anticancer cocktail after drainage of the abdominal cavity and abdominal wall. Among the present 24 cases, (A) was applied in 17 cases, and (B) in 7 cases. The inhibitory effect on ascites production was 87.5% or 21/24 cases, specifically 88.2% (15/17) in the (A) group and 85.7% (6/7) in the (B) group. There were no particular side effects. PMID- 3113339 TI - [A comparative clinical trial with tegafur plus lentinan treatment at two different doses in advanced cancer]. AB - In order to evaluate the clinical efficacy of combined tegafur plus lentinan treatment, a comparative trial was performed on patients with advanced cancer using two different doses, a conventional-dose group and a high-dose group. Thirty-four patients were evaluable in this trial. The doses of medication were 600 mg of tegafur p.o. daily and 1-2 mg of lentinan i.v. weekly in the conventional-dose group, and 1,200-800 mg of tegafur p.o. daily and 4 mg of lentinan i.v. weekly in the high-dose group. The response was evaluated using the criteria of Koyama. The response rates were 14.3% for the conventional-dose group and 25.0% for the high-dose group, although no statistical difference was observed. Acute toxicities such as oppression in the anterior chest and dryness of the throat, which were considered to be probably due to lentinan, were noted in patients given rapid administration with 20 ml of solution. However, these effects disappeared with slow-drip infusion using 100-200 ml of solution. These results suggest that the combined tegafur plus lentinan treatment would be better administered at a dose higher than the conventional one for the treatment for advanced cancers. PMID- 3113340 TI - [Multihospital randomized study on adjuvant chemotherapy with mitomycin C and futraful or UFT in gastric cancer (Part 1). Comparison between futraful and UFT. North Kyushu Co-operative Study Group for Cancer Chemotherapy)]. AB - The present study was undertaken to evaluate the effect of postoperative adjuvant chemotherapy for 232 cases of gastric cancer by a co-operative study group consisting of 21 hospitals. The present paper describes the side effects and the 2-year survival rates in patients. Side effects observed during long-term treatment with Futraful or UFT were considered to be minor, although incidence of toxicity in the UFT group was slightly higher than in the Futraful group. As for 2-year survival, elevated survival was found in stage III cases of poorly differentiated adenocarcinoma. This suggested that UFT is more useful than Futraful. PMID- 3113341 TI - [Phase I study of natural interferon-gamma]. AB - We report a clinical study of toxicity and pharmacokinetics of intravenously administered natural interferon-gamma. Twenty three cases with metastatic cancer were given interferon-gamma at doses of 10 X 10(4)-400 X 10(4) IU in single injection. Another twenty three cases were administered at doses of 5 X 10(4)-50 X 10(4) IU/day every day for thirty days. Side effects associated with natural interferon-gamma administration were qualitatively similar to those previously reported for alpha, and beta interferon treatment. After intravenous injection, interferon-gamma was cleared monoexponentially with a short half-life of 120 minutes from the circulation. One case with disseminated thyroid cancer showed minor response. PMID- 3113342 TI - [Phase II study of natural interferon-gamma. Natural Interferon-gamma Cooperative Study Group]. AB - Naturally produced interferon-gamma was evaluated in 187 cases with advanced cancer. Interferon was given by the i.v. routes in doses ranging from 1 X 10(5) IU to 2 X 10(5) IU/day daily or every other day for more than 2 months. Overall, clinical anticancer spectrum, effectiveness, toxicities, and pharmacokinetics were similar to that seen with preparations of interferon-alpha, and beta. PMID- 3113343 TI - [A case report of successful immunochemotherapy of metastatic renal cell carcinoma using UFT and PSK]. AB - The authors have monitored a case of renal cell carcinoma metastatic to the supraclavicular cavity over a twenty-year period following surgical removal of a cancerous kidney. The subject was a 67-year-old male who had his right kidney removed in 1963 because of renal cell carcinoma. In September of 1983, complaints of pain and an enlarged tumor in the left supraclavicular cavity during a physical examination led to a pathological diagnosis of clear cell carcinoma. Although chemotherapy using FT-207+ PSK was ineffective, there was a response to UFT+ PSK therapy which was deemed effective according to the criteria of Koyama and Saito. The findings suggested that UFT was effective in this case. PMID- 3113344 TI - [Comparative clinical studies of colorectal tumor tissue and normal tissue following arterial injection of tegafur]. PMID- 3113345 TI - Assessing the health effects of potential exposure to PCBs, dioxins, and furans from electrical transformer fires: the Binghamton State Office Building medical surveillance program. AB - A medical surveillance program has been established for 482 persons who were potentially exposed to polychlorinated biphenyls (PCBs), dibenzo-p-dioxins, and dibenzofurans from an electrical transformer fire in a Binghamton, NY office building in 1981. Blood samples were analyzed for serum concentrations of PCBs and for biochemical and hematologic parameters at the time of the fire and 9 to 12 mo later. Firefighters and individuals who were in the building for 25 hr or more were also asked about post-fire symptomatology and examined after 1 yr for disorders of the skin, eyes, liver, and neurologic system. The results indicated that reported exposure was positively related to mean serum PCB levels (p = .004). The means and individual values, however, were within the range reported by other studies of persons with no unusual exposures. Significant correlations were observed between serum PCB concentrations and levels of liver enzymes and lipids, but mean levels of these biochemical parameters were not associated with reported exposure after adjustment for relevant covariables. Approximately one half of those examined had skin lesions, but no cases of chloracne were detected, and there was no clinical evidence of any other exposure-related systemic disorder. The data suggest that exposure to contaminants from the building did not result in substantial absorption or cause any major short-term health effects. PMID- 3113346 TI - [Responses of the trachea and ileum of guinea pigs sensitized to the administration of antigen, in the presence of different drugs]. PMID- 3113347 TI - [Prognostic factors and risk of recurrence in a series of 385 patients with superficial bladder carcinoma treated with thiotepa, adriamycin or cisplatin]. PMID- 3113348 TI - Heterotopic heart-unilateral left lung transplantation in dogs. AB - A technique is presented for transplantation of the heart and left lung in the canine model. Preservation of the recipient's heart and right lung allowed heterotopic en bloc transplantation of the donor organs, thus preserving the normal respiratory pattern and obviating the need for cardiopulmonary bypass. Four experiments were performed to develop the surgical technique. The mean survival of the remaining 10 dogs studied was 23 +/- 28 days (range 3 to 91 days). The transplanted heart and lung could be investigated as in orthotopic heart-lung transplantation; bronchoscopy with bronchoalveolar lavage and endobrachial biopsy as well as endomyocardial biopsy were performed by standard approaches. This model is suitable for physiological and immunological long-term observations of cardiopulmonary transplantation in dogs. PMID- 3113349 TI - [Extend or restrict the indications for myocardial revascularization?]. PMID- 3113350 TI - [Exercise test and ventricular tachycardia: the French experience]. AB - The incidence of severe ventricular arrhythmia requiring electric shock or prompt intravenous therapy was evaluated during or immediately after 458,000 exercise tests performed in 46 french centres between 1975 and 1985; 177,000 tests were performed exclusively in cardiac patients during supervised exercise training sessions. Sixty cases of severe arrhythmia (ventricular fibrillation 23, ventricular tachycardia 35, asystole 2) occurred (1/7600 tests). One or several electric shocks were necessary in 35 cases. Six patients died (1/76,333 tests), 2 of them during training sessions; 5 had phase II or III myocardial infarction, and the 6th patient had moderately tight valvular aortic stenosis. The five coronary patients were taking various anti-arrhythmic drugs. Among the 54 survivors, 14 were lost sight of and 4 died, 2 of these suddenly including one who passed away during a bicycle ride. All others are alive after a 3.25 +/- 2.9 years follow-up. The association of a multiple-vessel disease with an extensive fibrous plaque is a syndrome that is highly sensitive but fortunately little specific in predicting severe arrhythmia during exercise tests. PMID- 3113351 TI - [Outcome of 195 patients with Wolff-Parkinson-White syndrome]. AB - Between 1974 and 1984, 207 patients with Wolff-Parkinson-White syndrome (WPW) were admitted to our hospital department; 195 of them were followed up for periods ranging from 1 to 12 years (6 years in children, 3 years and 9 months in adults on average); 160 had undergone electrophysiological exploration. Fifty seven patients were less than 16 years old: 7 died, including 6 with associated congenital heart disease; an asymptomatic 12-year old girl died suddenly while taking part in a sporting event. The signs of WPW disappeared in 5 out of 10 children under 1 year of age. One hundred and thirty-eight patients were older than 15: 15 of them died, but only 3 deaths were related to WPW: one was consecutive to surgery for WPW and one to fulguration; the third patient died of WPW tachyarrhythmia; the refractory period of his Kent's bundle was short, but his compliance with treatment was irregular. We found no correlation between changes in functional symptoms and Kent's bundle refractory period values; paradoxically, the frequency of attacks and resistance to treatment was higher in cases with long refractory period. On the whole, this series confirms that WPW usually is a benign disease. However, the risk of sudden death, of which it offers an example, indicates that all patients with WPW should be evaluated with at least an exercise test and, depending on its results or on the socio professional context, an electrophysiological exploration. PMID- 3113352 TI - [Prognosis of surgically treated infectious endocarditis]. AB - The prognostic factors in infective endocarditis patients who underwent surgery in the acute stage were evaluated from the records of 189 cases of native valve endocarditis operated upon between 1970 and 1986. Surgery had been performed before June 30, 1982 in 105 patients (group 1) and since July 1, 1982 in 84 patients (group 2). Group 2 only differed from group 1 in that the proportion of negative blood cultures was lower (13.7% vs 35%; p less than 0.01) and that of subjects older than 70 was higher (11.6% vs 5.7%; p less than 0.01). 105 patients (66 in group 1, 39 in group 2) had been operated upon during the first 6 weeks of antibiotic therapy ("early surgery"), while 84 patients (57 in group 1, 27 in group 2) had been operated upon between 7 and 24 weeks from the beginning of antibiotic therapy ("semi-early surgery"). Hospital mortality was 23.6% in group 1 (29/123) as against 10.6% in group 2 (7/66; p less than 0.05). The difference in mortality between the two groups was significant only in early surgery patients (33.3% vs 7.7%; p less than 0.01) and in patients operated upon while the infection was active with presence of pathogens in valve cultures (47.4% vs 7.7%; p less than 0.05). A study of mortality factors showed that the operative prognosis did not depend on the type of valve replacement performed or on the pathogen involved, but solely on the degree of cardiac failure before surgery. The post-hospital course was evaluated in group 1 patients followed up during 61.8 months on average.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113353 TI - [Obstruction of the left coronary branch. Ergometric, hemodynamic and angiographic findings]. AB - The authors present 6 personal cases of complete obstruction of the left main stem coronary artery and review the main epidemiological, clinical, ergometric, haemodynamic, angiographic and therapeutic data concerning this condition which is uncommon (0.66% of patients who underwent coronary angiography for angina in this series). This series had a number of special features. Clinical symptoms were moderate, consisting of exercise-induced aggravated angina, except in one patient with a history of anterior infarction complicated by regressive initial heart failure with residual angina. For this reason, all patients were able to perform a standard exercise-test on an ergometric bicycle without any problem. As the exercise test revealed major abnormalities, extreme precautions were observed when coronary angiography was performed, but no incident occurred in any of the 6 patients. Haemodynamic data were normal in 4 cases and altered in 2 cases. The important role played by collateral circulation must be stressed; it is probably under evaluated at arteriography. The absence of lesion of the right coronary artery is thought to facilitate the development of a collateral vascular network. Five patients were operated upon, made an uneventful recovery and were followed up for 19, 42, 17, 5 and 2 months respectively: all were symptom-free under medical treatment. In 3 out of these 5 patients who underwent a post-operative exercise-test all parameters showed excellent results; however, the 4th patient proved unadaptable to exercise, and ECG showed persistent ischaemia due to a very poor distal coronary bed; in the 5th patient, under diltiazem, the results on ischaemia and on the circulatory signs of heart failure were very good.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113354 TI - [Automatic quantitative analysis of myocardial tomography thallium-201 scintigraphy]. AB - An automatic and quantitative analysis method for tomographic scintigraphy was applied to 104 patients with myocardial infarction (anterior 37, inferior 67, lateral 20, involving 2 territories in some cases). All patients underwent exercise and redistribution scintigraphy and coronary arteriography which served as reference. Two types of tomographic sections were used: 2 short axis sections exploring the left ventricle at different levels, and 1 apical section at a right angle with the first ones. A circumferential analysis program studied the isotopic activity of each section and drew an activity profile curve which was compared with those obtained in normal subjects. Exercise curves proved superior to redistribution and wash-out curves and were therefore used exclusively. Two sectoring methods for territories with infarcts were defined: conventional sectoring, which gives a 90 degrees angle to the anterior region and a 180 degrees angle to the inferior lateral region, and real sectoring established from the scintigraphic abnormalities observed in patients whose infarction was not accompanied by significant lesions in other territories. Real sectoring divides the territory into two regions (anterior and infero-lateral) and determines the extension territory and the territories specific to each necrotic region. The sensitivity and specificity of these two methods for the diagnosis of necrosis and the detection of a significant abnormality (greater than 70% stenosis, or necrosis) in a territory other than the one with infarct were compared. In the diagnosis of infarction: conventional sectoring sensitivity 92%, specificity 46% for anterior infarcts, 94% and 25% for inferior and lateral infarcts; real sectoring 94% and 63% respectively for anterior infarcts, 92% and 68% for inferior infarcts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113355 TI - [Continuous emission Doppler study with spectrum analysis in the evaluation of aortic stenosis in adults. Apropos of 30 cases]. AB - The value of continuous wave doppler with spectral analysis for the evaluation of aortic stenosis in adults being controverted, we analyzed prospectively the results obtained in 30 consecutive elderly patients (mean age 63 years) investigated by invasive and non-invasive methods. In 24 patients who underwent both ultrasonic and catheter examinations, the correlation between mean gradients measured by catheterization and calculated separately by doppler was 0.80. For a semi-quantitative evaluation of the aortic valve area, we suggest to use an additional severity index R calculated from doppler data (R = mean gradient/maximal instantaneous gradient) which correlated well (r = -0.68) with the aortic valve area. In our experience, this index makes it possible to separate patients with a less than 0.75 cm2 aortic valve area, as calculated from Gorlin's formula (R greater than 0.65) from patients with a more than 0.75 cm2 aortic valve area (R less than 0.65), irrespective of the associated cardiac index. It is concluded that the doppler ultrasound method provides a highly satisfactory evaluation of transaortic gradient, as well as a semi-quantitative evaluation of the stenotic aortic ostium in the majority of elderly patients with aortic stenosis. PMID- 3113356 TI - [Cardiac rupture in acute myocardial infarction. Various clinico-anatomical types in 42 recent cases observed over a period of 30 months]. AB - Forty two cases of complete or incomplete rupture of the free left ventricular wall were reviewed in a group of 136 patients who died of acute myocardial infarction in a Coronary Care Unit and who underwent autopsy examination over a 30 month period. Four groups were distinguished on macro and microscopic features of the rupture based on a previously defined classification established by former studies: type I rupture (13 cases) with an almost direct trajectory with little dissection and bloody infiltration of the myocardium; type II (13 cases) with a multicanalicular trajectory and widespread myocardial dissection and bloody infiltration; type III (9 cases) in which the orifice of rupture is protected by an intraventricular thrombus or a pericardial symphysis; type IV (7 cases) with incomplete epicardial, endocardial or intramyocardial rupture which never was transparietal. The clinical characteristics (age, sex, time interval before admission to the coronary care unit, previous history, ECG location of the myocardial infarcts, clinical course, Killip classification, treatment and ECG changes) and anatomical findings (weight of the heart, presence of haemopericardium, previous infarction or aneurysm, location of the infarct, presence of intraventricular thrombus or ventricular septal defect, number of vessels with over 75 p. 100 obstruction and topographical location of the rupture) were compared. The type I ruptures had smaller infarcts and a quicker terminal illness with rapid evolution to cardiac tamponade. In type II ruptures, the infarcts tended to be bigger, sometimes associated with septal rupture and the terminal illness was longer lasting than in the previous group, reflecting a longer evolution towards cardiac tamponade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113357 TI - [Comparative study of the effects of verapamil and propranolol therapy in 16 cases of obstructive hypertrophic myocardiopathy]. AB - In a randomized, double-blind, cross-over study with plasma drug assays, 16 patients (11 men, 5 women; mean age 48.56 +/- 3.61 years) presenting with hypertrophic obstructive cardiomyopathy confirmed by echocardiography, left ventriculography and left intraventricular gradient measurement were treated with verapamil 480 mg/day or propranolol 320 mg/day. Both treatments produced functional improvement (p less than 0.01) which was more distinct with verapamil (NS). No changes in cardiothoracic index, echocardiographic parameters and Sokolow's index were observed. Mean total heart work during exercise, which was 1,197.27 +/- 135.89 watts before treatment, increased to 1,260.91 +/- 146.60 watts under propranolol (NS) and to 1,344.09 +/- 171.06 watts under verapamil (NS). Maximum heart rate during exercise, which was 162.3 +/- 3.46 beats/min before treatment, was reduced to a greater extent by propranolol (122.1 +/- 6.6 beats/min; p less than 0.001) than by verapamil (147.7 less than 5.08 beats/min; p +/- 0.01). The two treatments did not significantly modify ventricular arrhythmia, arterial and capillary pulmonary pressures, mean aortic pressure and left ventricular end-systolic pressure. Cardiac index, unchanged under verapamil, fell from 2.98 +/- 0.16 1 X min-1 X m-2 to 2.60 +/- 0.11 1 X min-1 X m-2 under propranolol (p less than 0.05). The left intraventricular gradient present in 5 patients at rest and during exercise, was reduced by both drugs. The gradient under isoprenaline (n = 16), which was 162.07 +/- 18.77 mmHg before treatment, fell to 93.86 +/- 24.48 mmHg with propranolol (p less than 0.05) and to 128.86 +/ 18.22 mmHg with verapamil (p less than 0.05). Left ventricular ejection fraction, mean circumferential fibre shortening speed and compliance coefficient remained unchanged under both drugs (NS). Left ventricular diastolic function, evaluated by radioisotope angiography in the last 9 patients, was most often improved by verapamil (NS). Verapamil was better tolerated generally and by the heart than propranolol. No correlation was observed between plasma verapamil levels and clinical results. Low plasma propranolol levels were often noted in non-responders, suggesting a need for treatment with high doses. It is concluded that at the dosage level used in this study propranolol and verapamil were equally effective, but there were individual variations in best response to one or the other of these two drugs. PMID- 3113358 TI - [Oral flecainide in the treatment of refractory arrhythmias. Long-term follow-up of 98 patients]. AB - Oral flecainide was administered to 98 patients with arrhythmias regarded as resistant to other antiarrhythmic agents: quinidines (82), propafenone (40), beta blockers (30), amiodarone alone (38) or combined with a class I compound (19). Therapeutic effectiveness was assessed on clinical date, repeated Holter recordings (64 patients), exercise tests (8) and electrophysiological exploration (15). Mean follow-up was 11.7 +/- 11 months; the patients treated have now been followed up for 18.2 +/- 12 months (range: 7-58 months). Fifty-three patients had atrial arrhythmia (fibrillation or flutter in 45, atrial tachycardia in 8). Flecainide was effective in 26 patients (49%) and ineffective in 27 (51%). There was no significant difference in dosage between these 2 groups: 231 +/- 62 mg/day and 265 +/- 61 mg/day respectively. Paroxysms of re-entrant junctional tachycardia were controlled in 6 of the 8 cases observed. Eleven patients presented with Wolff-Parkinson-White syndrome: treatment was successful in the 3 patients with atrial fibrillation and in 8 of the 10 patients with orthodromic reciprocating rhythms. Among 30 patients with episodes of ventricular tachycardia, 9 (30%) responded to flecainide and 21 (70%) failed to respond. Flecainide reduced the repetitive forms by more than 90% in 7/15 patients and suppressed exercise-induced ventricular tachycardia in 2/8 patients. Fifteen out of 18 patients had ventricular tachycardia reproducible by programmed stimulation; under flecainide, the ventricular tachycardia spontaneously recurred in 4 cases, was provoked by stimulation in 5 other cases, was more easily inducible in 3 cases and was not inducible in a sustained manner in the last 3 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113359 TI - [Massive hemolysis and acute mitral insufficiency one year following mitral valve repair. Apropos of a case]. AB - The authors report a case of massive haemolytic anaemia with acute mitral valve regurgitation and left cardiac failure, which occurred one year after surgical reconstruction of the mitral valve for rupture of smaller leaflet chordae. Anaemia, mitral regurgitation and cardiac failure disappeared after mitral valve replacement, using a Carpentier Edwards No. 29 valve. Haemolytic anaemia following mitral valve reconstruction is exceptional. It seems to be due to the suture material lying in a turbulent regurgitation stream when mitral incompetence develops again. PMID- 3113360 TI - [Rupture of the left ventricle into the free pericardium in the early stage of a myocardial infarction. Diagnosis using echocardiography and surgical treatment]. AB - A case of subacute left ventricular rupture on the 4th day of an inaugural antero septal infarction in a 63-year old woman is reported. The diagnosis, suggested by cardiovascular collapse with acute tamponade, was confirmed by echocardiography. Haemodynamic stability was maintained by needle aspiration followed by pericardial drainage, and right heart catheterization long enough for the patient to be transported to a Cardiovascular Surgery unit where surgical repair was successfully performed 9 hours after the rupture. The elements for a positive diagnosis, the value of echocardiography, the various surgical procedures and the favourable long-term prognosis in patients operated upon are discussed. PMID- 3113361 TI - [Cellular mechanisms of cardiac rhythm disorders]. PMID- 3113362 TI - [Reduction of auricular flutter by esophageal stimulation in a newborn infant]. PMID- 3113363 TI - [Mitral atresia. Anatomical aspects]. AB - This study is devoted to a series of 30 anatomical cases of mitral atresia. The left atrium was dilated in 5 cases and hypoplastic in 25. The interatrial ostium was small in 50% of the hearts. Left atrio-ventricular concordance was present in 29 cases, as against 1 case of discordance. There was no atrio-ventricular connection in 29 cases, and the mitral valve was imperforate in 1 case. Connections between the tricuspid valve and the main ventricle were normal in 26 hearts. The tricuspid valve straddled the septum in 4 cases. Five hearts had two ventricles, 25 had a single ventricle. Nine hearts showed no ventriculo-atrial atresia. The main vessels were normally located in 1 case, transposed in 2 and originated in the right ventricle in 2 cases; in the 5 hearts with single ventricle the two main vessels arose from the main cavity. Seventeen hearts had an atresic aortic valve and a hypoplastic ascending aorta; the pulmonary artery arose from the right ventricle in 1 case and from the main chamber of a single ventricle heart in 15 cases. The pulmonary valve was atresic and the aorta arose from the main chamber of a single ventricle heart in 4 cases. PMID- 3113364 TI - [Cardiovascular dysplasia in Noonan's syndrome. Apropos of 64 cases]. AB - The multiple malformation syndrome with characteristic facies described by Jacqueline Noonan in 1963 is one of the most commonly encountered syndromes in paediatric cardiology. The series presented here comprises 64 cases, almost a quarter of which were familial (6 families). The morphotype (Turner phenotype with hypertelorism) can easily be recognized, but the variations, progressivity and resemblance to some similar syndromes imply a detailed analysis of a wide range of discriminant features. Short stature and webbed neck are less frequent than in Turner's syndrome, while mental debility and, mostly, cardiovascular lesions are much more frequent (the latter are present in 50-60% of the cases). The most typical cardiovascular lesion is pulmonary valve stenosis with dysplastic leaflets, or "atypical pulmonary stenosis syndrome", characterized by a curious electrical axis and above all, by left ventricular myocardiopathy with very peculiar deformations at ventriculography and 2D-echocardiography. In our series, myocardiopathy was even more frequent than dysplastic pulmonary valve stenosis (71.8% versus 64%). The dissemination of dysplastic lesions must be emphasized. They involve the aorta much more often than is usually reported (one third of the cases); lesions of the lymphatic system are less frequent but may be severe. Occasionally, entirely different heart diseases, such as Fallot's tetralogy, are encountered. Owing to the relationship between its lesions and those of other multiple malformation syndromes, notably those of the phakomatosis group, and to the possibility of borderline cases with these syndromes, or even with other dystrophies, such as Williams-Beuren dystrophia, the cardiovascular dysplasia of Noonan's syndrome must be classified within the vast group of histodysplasias which are embryonic diseases of the "layers" or "neuro-ecto mesodermoses" of unknown genetic mechanism. PMID- 3113365 TI - [Left ventricle in Noonan's syndrome. Electro-vecto-echo and angiocardiographic aspects]. AB - The electrocardiographic features of Noonan's syndrome have been known for several years, but the discordance between these electrical findings and the underlying haemodynamic disorders remains unexplained. In an attempt to elucidate the genesis of electrical abnormalities, we present here a retrospective study of 14 children with Noonan's disease, aged from a few days to 16 years and evaluated by electrocardiography, vectography, one- or two-dimensional echocardiography, angiography and His bundle electrophysiology. The electrocardiographic abnormalities observed concerned ventricular depolarization and intracardiac electric conduction with, notably, a QRS axis directed towards the right upper part of the electric field and a first degree infra-hisian atrioventricular block (His bundle potentials). Vectography showed in some cases an image of inferior pseudo-necrosis due to the absence of initial inferior forces; this image is highly characteristic. In other cases the QRS loop showed an image of left segmental block which is unusual in this type or cardiac pathology (pulmonary stenosis with or without atrial septal defect of the ostium secundum type). PMID- 3113366 TI - [Interauricular communication with severe pulmonary hypertension in children. Apropos of 9 cases]. AB - The authors report 9 cases of atrial septal defect with sever pulmonary hypertension in 7 girls and 2 boys under 10 years of age. These cases represent 3.5% of the 255 cases of atrial septal defect in this age group seen at the Hopital Cardiologique of Lille between 1970 and 1985. Group I comprised 3 children with obstructive pulmonary hypertension from the start; two died, one is still alive after 3 years. Group II was composed of 3 children who presented, at first haemodynamic evaluation, with severe but non-obstructive pulmonary hypertension; the hypertension rapidly became obstructive in 2 of them despite digitalis-diuretic therapy; the third child died after surgical correction. The 3 children in group III had normal or slightly raised pulmonary arterial pressure at first haemodynamic evaluation; one of them initially had a right ventricle pulmonary artery functional gradient of 45 mmHg, which did not prevent the subsequent development of obstructive pulmonary hypertension; the other 2 patients were operated upon 10 months and 4 years later respectively, as they presented with severe pulmonary hypertension; one of these 2 children died postoperatively, the third one developed obstructive pulmonary hypertension. Contrary to what is generally believed, severe pulmonary hypertension is not exceptional in children with atrial septal defect, and it has a poor prognosis. The mechanism underlying the development of this pulmonary hypertension is unclear, but individual susceptibility to excessive blood flow is probable, as is the role played by bronchopulmonary infections frequently noted in these patients' history. PMID- 3113367 TI - [Evaluation of the size of atrial septal defects by subxiphoid approach in two dimensional echocardiography]. AB - In order to assess whether subxiphoid two-dimensional echography is a reliable method to evaluate the size of atrial septal defects (ASD), we compared echocardiographic and per-operative measurements. We then tried to determine whether the size of the defect correlated with the importance of the shunt at catheterization. The records of 23 patients (16 female, 7 male) operated upon for uncomplicated ASD were selected. Mean age was 23.5 +/- 17.3 years (range: 8 months to 62 years). Two-dimensional echocardiography was performed by the "reversed" subxiphoid route, using two projections: "4-cavity section" and an oblique section, perpendicular to the first one, through the atria and the aortic arch. The greater echographic diameter was compared with the greater diameter measured at surgery. The ASD area, assimilated at echography to a circle, was compared with the per-operative area (elliptic or circular opening depending on whether 1 or 2 dimensions were available). Per-operative diameter and area related to body surface were then correlated with the haemodynamic QP/QS ratio. The location of the ASD proved correct in all cases (ostium secundum 19, sinus venosus 3, inferior vena cava 1). Mean diameters were 22.4 +/- 6.4 mm (range: 12 40 mm) at echocardiography and 23.6 +/- 7 mm (range: 12-45 mm) at surgery. The mean area at echography was slightly superior to that measured per-operatively: 4.3 +/- 2.6 cm2 (1.4-12.5 cm2) versus 3.8 +/- 2.1 cm2 (1.4-8.9 cm2). There was a very good correlation between echographic and per-operative diameters (r = 0.91; p less than 0.001) and areas (r = 0.89; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113368 TI - [Origin of the common pulmonary vein, septation of the primary sinus venosus atrial situs and theory of the "sinus man"]. AB - Situated at the entry to the heart, the sinus venosus regulates at an early stage the distribution of the veins. Originally symmetrical, it receives on either side an omphalomesenteric vein, a common cardinal vein (duct of Cuvieri, ductus cuvieri) and a common pulmonary vein. This symmetrical pattern disappears with the obliteration of the rough right pulmonary vein and the invagination of the left ductus cuvieri into the sinusal cavity. Thus, the pulmonary venous blood is kept on the left side and the systemic venous blood is transferred to the right side. This is the usual situs solitus arrangement. Situs inversus is the opposite arrangement. In situs ambiguus the original symmetry is preserved. A sufficiently early cauterization of the left wall of the sinus venosus prevents the left ductus cuvieri from invaginating and results in "absence of coronary sinus"; this arrangement, where part of the original symmetry is preserved, is in fact similar to situs ambiguus. The situs of the liver and stomach is thought not to be determined by these organs but imposed to them by the sinus venosus, more precisely by the invagination--or lack of invagination--of a ductus cuvieri. This would explain the concordance between their situs and that of the sinus venosus and atria. It would appear that two errors are frequently made: the common pulmonary vein is said to originate from the left atrium, whereas it originates from the sinus venosus and only belongs to the left atrium when the sinus is incorporated in the atrium; the transverse septation of the sinus is incorporated to a shift to the right of the left sinoatrial fold which separates the sinus from the primitive atrium. This fold is indeed displaced to the right, but it is more distal and corresponds, in fact, to the cephalic border of the left ductus cuvieri, and its shift is produced by the invagination of that duct. PMID- 3113369 TI - [Anomalous origin of the left coronary artery. The form in infants]. AB - Twenty-four cases of anomalous origin of the left coronary artery from the pulmonary artery are reported. These cases were collected over 27 years divided into three 9-year periods according to the years of the initial studies. The clinical aspects and diagnostic investigations (notably echocardiography, myocardial radioisotope imaging and various angiographic procedures) are reviewed; aortography seems to be, even now, the best exploratory method. Treatment is analyzed according to the periods of observations. From the earliest cases it may be concluded that ligation proved ineffective in infants and medical treatment often failed. Progressively, medical treatment with digitalis (now better controlled), potassium-sparing diuretics and vasodilators has become more effective. On the other hand, direct reimplantation of the left coronary artery onto the aorta has become the preferred surgical procedure. Among the 8 most recent cases (seen between 1977 and 1986), 4 were cured by medical treatment under the age of 3 and subsequent reimplantation. In the other 4 patients asystolia responded to medical treatment, and these children are now awaiting reimplantation. PMID- 3113370 TI - [Coronarocardiac fistula disclosed neonatally. Apropos of 2 cases]. AB - Two cases of fistula between a coronary artery and the cardiac cavities (right coronary artery-right atrium, and right coronary artery-right ventricle) are reported. They were revealed by cardiac failure developed shortly after birth. The diagnosis was confirmed by two-dimensional echocardiography and angiography. In both cases closure of the fistula, with atriotomy in one case and coronary arterotomy in the other case, could be performed before the age of 1 month. The post-operative result was satisfactory in the two infants. Cases in which blood flow through such fistulae is important enough to cause cardiac failure in the newborn are exceptional. Nevertheless, this diagnosis must be borne in mind, as it requires rapid surgical correction. PMID- 3113371 TI - [Atheromatous lesions of the proximal aorta. Severe complications of homozygous type IIa hypercholesterolemia in children]. AB - Coronary lesions with atheromatous deposits occurring in later childhood characterize homozygous type IIa hypercholesterolaemia and condition the somber prognosis of a disease which affects one subject in a million. However, aortic lesions are constantly found, as shown by routine ultrasonographic and angiographic studies in these children. The walls of the proximal aorta are cardboard-like and thick, the origin of the aorta is narrow and the semilunar aortic valves are thickened. The valvular or supravalvular aortic gradient may be considerable; it is often progressive, but is sometimes stabilized or made regressive by medical treatments combined with plasmapheresis or porto-caval shunt. Aortoplasty or aortic valve replacement being difficult to perform in these patients, more aggressive therapeutic procedures, such as liver or heart transplantation, have been suggested. The last generation cholesterol-lowering drugs seem to offer some hope of success. PMID- 3113373 TI - [Current results of the treatment of transposition of the great vessels. Apropos of a series of 168 cases including 138 physiologic corrections]. AB - This study takes stock of the current results of physiological correction (Mustard's or Senning's operation) in simple transposition of the great vessels, at a time when anatomical corrections, or detranspositions, are developing. Between January 1, 1974 and December 31, 1984, 168 neonates with simple transposition of the great vessels were operated upon and followed up for a mean period of 3.67 years (up to 11 years and 10 months). Thirty of them died before correction (12.7% mortality rate with palliative surgery) and 15 immediately after corrective surgery (11.2%). Among the 111 children who survived corrective surgery, the results were satisfactory in 62.7%, fair in 17.8% and poor in 10.2%; the late mortality rate was 9.3%. Post-correction morbidity mainly consisted of mechanical complications suspected in one-third of the patients (with 3 consecutive deaths) and heart rhythm disorders (50% of patients in this series had abnormal Holter recordings), with predominance of atrial rhythm disorders (regression of sinus rhythm was 3.82% per annum). This, after correction the survival curve underwent an actuarial regression of 1.31% per annum. This primary and secondary morbidity and mortality justifies a switch to anatomical corrections the results of which remain to be fully evaluated. PMID- 3113372 TI - [Intestinal malformations and congenital heart diseases]. AB - A series of 21 patients with both congenital heart disease and intestinal malformation seen over a 12-year period is reported. The intestinal malformations were: anorectal malformations (11 cases), duodenal atresia (5), omphalocele (4) and common mesentery (1). Congenital heart diseases consisted of: atrial septal defect (ASD) (10 cases), ventricular septal defect (VSD) (2), tetralogy of Fallot (2) and miscellaneous cardiopathies. In patients with anorectal malformations ASD and VSD predominated (6/11 cases) and multiple malformations syndromes were present in 8 cases, including trisomy 13, Vater syndrome, skeletal (4), neurological (3) and renal abnormalities (3); 3 children died. Duodenal atresia was always associated with left-to-right shunt: VSD (3), ductus arteriosus (2), complete atrioventricular canal (1) and trisomy 21 (2); one child died. Omphalocele coexisted with VSD (2), tetralogy of Fallot (1), dual outlet right ventricle (1), trisomy 21 (1) and multiple malformations syndromes (3); 2 children died. The patient with common mesentery had left-to-right shunt. Comparison of this series with data from the literature showed that children with congenital heart disease have a much higher incidence of intestinal malformations than those with normal heart and that they frequently present with multiple malformations (chromosome aberrations or multiple organ lesions). This multiple malformation complex is particularly common in anorectal malformations where the incidence of congenital heart diseases is 9 to 14%, with predominance of VSD and tetralogy of Fallot. In patients with duodenal atresia trisomy 21 is extremely frequent, and the incidence of cardiopathies is 18%; in the absence of trisomy 21 the cardiopathy is complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113374 TI - [Restrictive ostium secundum: a new fetal malformation syndrome]. AB - Echocardiographic examination of a 23 weeks' hydropic fetus disclosed abnormal kinetics of the valve of the foramen ovale. This valve was constantly bulging out, dome-like, into the left atrium, and on TM-mode tracings in transatrial projection the alpha and beta peaks which occur respectively during the opening and closure of the atrioventricular valves throughout fetal life were missing. This anomaly suggested that the ostium secundum was restrictive; the foramen ovale itself was not restrictive. Such abnormal kinetics have not been encountered among 16 other cases of hydrops fetalis of cardiac or other origin, or in a control series of 81 normal fetuses, which clearly shows that the restriction was primitive. At birth, the child presented with aneurysm of the foramen ovale, probably due to the restrictive ostium secundum. PMID- 3113375 TI - [Left ventricular function and cardiovascular adaptation to exercise in young sportsmen]. AB - In order to find out whether the expression "sports heart" can be used in children and if so, to give an objective definition of it, we studied a group of 40 young people (mean age 12.2 +/- 1.6 years) subjected to intensive training and practising sports regularly, i.e. about 12 hours of physical activity per weeks on average. The sports practised were mainly tennis among boys and ice-skating among girls. A group of 40 subjects with similar characteristics but no particular physical training was studied simultaneously and served as control. These 80 young people had normal heart structure. All underwent routine cardiovascular examinations (physical, radiological, electrocardiographic), complete one - and two - dimensional echocardiography to evaluate left ventricular function and an exercise-test on ergometric bicycle. No difference was found between the left ventricle of sportsmen and that of controls; in particular, there was neither dilatation nor parietal thickening in sportsmen, so that all functional values were the same. During exercise-tests sportsmen performed better than controls, with significantly longer duration of effort and greater maximal oxygen consumption. However, heart rate at rest, then during exercise and recovery, and variations in systolic blood pressure during exercise and in the 10 minutes which followed were identical in both groups. The only notable difference was a deeper fall in diastolic blood pressure in sportsmen, indicating a better opening of the peripheral vascular bed during exercise. It is concluded that there are few cardiovascular differences between trained sporting children and children with normal physical activity, probably because the relatively short training undergone does not leave sufficient time for most of the adaptation systems to become established. PMID- 3113376 TI - [Dilated cardiomyopathy: electrocardiographic forms]. AB - The shape of the QRS complex was analyzed in 90 cases of dilated cardiomyopathy and was divided into 6 electrocardiographic types which may be interpreted as follows: A predominant S wave in V2, V3 and V4 leads, surrounded by a reduced QRS voltage in the other leads was the most frequent characteristic pattern, being found in 31 cases (34.4%). This pattern coexisted with a lack of R wave progression from V1 to V4, with primary disorders of ST-T and with alterations in P wave. The deep S wave is probably due to a growth of vectors in the base of the left ventricle and in the septum in response to lesions in the rest of the myocardium. Second in frequency (22.2%) came left bundle branch block, with 20 cases. If to these are added the 19 cases of left anterior half-block observed, dilated cardiomyopathy appears as the major cause of the cardiac pathology that partially or completely interrupts the left branch. These cases also show that the lesions predominate in the left ventricle. The 14 cases (15.5%) of QS with elevated and convex ST-T betray extensive areas of fibrosis or necrosis. This pattern is characteristically located at the apex of the heart and associated with ventricular tachycardia. In 11 cases (12.2%) the QRS complex was normal in shape but associated with depressed ST-T and atrial disorders. This shows that the ventricular myocardium which produces QRS is neither badly damaged nor hypertrophic, but that repolarization is highly sensitive to the constant alterations of the subendocardial layers observed in dilated cardiomyopathy. Left ventricular hypertrophy was seen in 9 cases (10%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113377 TI - [Role of urokinase in the acute phase of myocardial infarction]. AB - The prourokinase-urokinase system physiologically contributes to fibrinolysis activation. It is therefore rational to envisage the use of urokinase in thrombotic diseases, and notably in the acute phase of myocardial infarction (MI) where coronary thrombosis is virtually constant. The main studies on this subject were published in 1975 and in 1985, thus reflecting the changes in therapeutic concepts that have occurred during these 10 years. The older studies concerned patients who were admitted within the first 12 hours of MI and had no early angiographic examination; the results were evaluated indirectly on clinical and enzymatic criteria and on the regression of electrical signs of myocardial suffering. The more recent studies concern patients who are treated at an early stage, often within the first 3 hours of the accident, on the basis of experimental data which favoured early coronary reperfusion as a means of protecting the myocardium; in these studies coronary arteriography is performed immediately after the thrombolytic treatment; computer-assisted studies of the left ventricular function are also carried out, so that the results of thrombolysis are expressed in terms of coronary patency and improvement in segmental kinetics. The results of these different sets of studies have proved to be similar with time. Urokinase, notably when injected intravenously, has a beneficial effect in the acute phase of MI when compared to the conventional treatment. The coronary reperfusion obtained with urokinase is favourable to the myocardium, and the sooner it occurs the better. This benefit is demonstrated by clinical, electrical, enzymatic and angiographic data. Thus, despite its cost, urokinase remains useful in the treatment of MI, notably because it is well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113378 TI - [Doppler echocardiography in dysfunctions of valvular prostheses: diagnostic and quantitative significance. Apropos of 20 cases]. AB - We present a retrospective study of 20 patients with cardiac valve prosthetic dysfunction who required reoperation and underwent pre-operative doppler echocardiography. There were 13 cases of mitral valve prosthesis (3 mechanical, 10 xenografts), 5 cases of aortic valve prosthesis (1 mechanical, 4 xenografts), 1 pulmonary valve bioprosthesis and 1 tricuspid valve mechanical prosthesis. Our purpose was to evaluate the diagnostic and quantitative value of this examination in prosthetic dysfunction by comparing doppler data with anatomical findings at surgery. The parameters measured were peak and mean pressure gradients in all cases, gradient half-decrease time and valve surface calculated therefrom in mitral and tricuspid valve prostheses. The results of doppler examination were compared with per-operative anatomical findings in 6 cases, and pre-operative haemodynamic exploration was performed in one case. The diagnosis of prosthetic stenosis was found to be correct in all patients, even in those with moderate stenosis. All leaks and their locations were diagnosed, except in a mitral valve mechanical prosthesis where leaking was detected by continuous doppler. 14 out of the 20 patients were reoperated upon without catheterization. These results suggest that doppler examination is a sensitive and specific method for evaluating cardiac valve dysfunction. However, variations in doppler results from one prosthesis to another make it necessary to perform pulsed and continuous doppler at the end of the operation to be used as reference if dysfunction is suspected subsequently. PMID- 3113379 TI - [Valvular replacement for isolated aortic stenosis. Predictive value of the preoperative cardiac index in survival]. AB - The immediate and long-term results of aortic valve replacement for pure or predominant aortic valve stenosis were evaluated in 186 patients operated upon since 1975 and followed for up to 10 years. This population fell into two groups depending on whether the pre-operative cardiac index was superior (group I, n = 111) or inferior (group II, n = 75) to 2.3 l/min/m2. There was no significant difference between the two groups as regards the immediate (i.e. within 30 days) post-operative mortality rate (6.6% vs 8.1% respectively). In contrast, the cardiac index proved to be a significant post-operative prognostic factor in aortic stenosis, since the probability of survival at 5 years was 96.4% in group I and only 71.7% in group II (p less than 0.001). This high rate of mortality in group II was exclusively due to myocardial dysfunction (sudden deaths included) in these patients with low cardiac index. When late mortality was analyzed according to age (over or below 60 years) and to pre-operative cardiothoracic ratio (over or below 50), these two criteria also proved to be significant prognostic factors. However, considering the poor prognosis of unoperated aortic stenosis, these long-term results in group II should encourage surgical treatment in many cases, even those with advanced cardiopathy. PMID- 3113381 TI - [Strategy of studies in pulmonary embolism]. PMID- 3113380 TI - [Permeability of venous aortocoronary bypasses one year after their implantation]. AB - For a short-term evaluation of the patency of aortocoronary bypass vein grafts, 54 consecutive patients who underwent this operation alone were examined, irrespective of their functional state, 12.4 +/- 2.1 months after surgery. Examinations included coronary arteriography, selective opacification of the graft and ventriculography. The patients were 47 men and 7 women who had coronary arteriography for stable angina pectoris (22.4%) or a recent episode of unstable angina (59.3%) or a recent myocardial infarction (18.5%). Coronary arteriography showed one-vessel (5.5%), two-vessel (27.8%) or three-vessel (42.6) disease or stenosis of the main left coronary artery (24.1%). The mean number of distal anastomoses in multiple-vessel patients was 2.6. Peri-operative mortality was 1.04%, and the proportion of peri-operative electrocardiographic signs of necrosis was 11%. At the time of control examination, 82% of the patients had few or no symptoms, and 88% were improved by at least one functional class. 79% (97/123) of distal venous anastomoses were patent. All anastomoses were patent in 59% (22/54) and all were occluded in 7% (4/54) of the patients. Localized stenosis of the graft was found in 11% and diffuse stenosis in 4% of the cases. The patency of vein grafts was higher when the distal bed was of normal size than when it was small or poorly visualized at the initial angiography (85% vs 62%, p less than 0.01), or when the diameter of the artery bypassed was greater than 1.3 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113382 TI - [Current risks of coronarography]. PMID- 3113383 TI - [Electrophysiological, hemodynamic and histological effects of fulguration on the ventricular myocardium in the dog]. AB - The myocardial repercussions of endocavitary fulguration depend upon the interaction of different physical phenomena. We studied the influence of energy level on the one hand and of the physical properties of the catheter (Ct) on the other hand on the cardiac effects of right endoventricular fulguration in the dog. A monopolar anodal shock was delivered in 12 dogs. Two levels of energy were applied: 25 J (group A, n = 6) and 100 J (group B, n = 6), and three Ct were used which differed in resistance (R) and active surface (S): Ct 1 (R = 0.3 omega, S = 12 mm2), Ct 2 (R = 0.3 omega, S = 2 mm2) and Ct 3 R = 2 omega, S = 13 mm2). Immediately after fulguration a significant rise of the right ventricular effective refractory periods was observed in group B only (193 +/- 28 vs 174 +/- 19 ms; p less than 0.03). Compared to baseline values, the systolic and diastolic pressures fell by 12% (p less than 0.01) and 18% (p less than 0.01) respectively in group A and by 33% (p less than 0.05) and 34% (p less than 0.002) respectively in group B. In contrast, there was no significant difference between variations of these parameters with the three types of Ct. The incidence of complex ventricular arrhythmia was higher in group B (5/6) than in group A (1/6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113384 TI - [Cardiac involvement in 2 cases of malignant non-Hodgkin's lymphoma. Course of cardiac involvement under chemotherapy]. AB - In a recently published post-mortem series the incidence of cardiac lesions in malignant lymphoma was estimated at about 8.7%. These lesions rarely produce specific cardiac symptoms; they usually are late manifestations of a disease with multiple secondary lesions or are discovered at autopsy. In most patients the lesions are not limited to the heart but represent the extension to that organ of a malignant lymphoma. We observed two cases of cardiac lesions secondary to malignant non-Hodgkin lymphoma and we were able to evaluate their response to chemotherapy. In the first patient the cardiac symptoms revealed the lymphoma; in the second patient the cardiac involvement was discovered 4 years after the lymphoma was diagnosed. In both cases the cardiac lesions were detected by two dimensional echocardiography. They presented as polypoid masses filling the right atrium and associated with periaortic thickening in the first case, and as a large heterogeneous mass including a tricuspid valve leaflet and extending to the free wall of the right ventricle in the second case. Pericardial effusion was present in the two patients. These echocardiographic findings were confirmed computerized tomography and catheterization. In the first case, followed up for one year, the echocardiographic images reverted to normality after chemotherapy. The second patient, unfortunately, did not respond to chemotherapy and deteriorated rapidly. PMID- 3113385 TI - [Asymptomatic recurrence of a left auricular myxoma. Apropos of a case]. AB - A case of asymptomatic recurrence, in a 23-year old female patient, of a left atrial myxoma surgically removed 7 years previously is reported. The initial tumour, revealed by lipothymias and progressive heart failure, had been diagnosed by TM-mode echocardiography. The myxoma had been entirely removed, together with part of the atrial septum around its pedicle. The recurrent tumour was discovered by chance during routine control echocardiography. Post-surgical recurrent cardiac myxomas are uncommon (5% of the cases), and they predominate in the left atrium, like the initial tumours. They develop more rapidly and may recur several times in succession, becoming increasingly aggressive and multiple, though most of them remain benign. They are thought to result from the proliferation of myxomatous cells in clusters disseminated within the cardiac walls. Echocardiography is the key to the diagnosis; it is also used for post-surgical follow-up. PMID- 3113387 TI - [Hydatid cyst of the right heart and post-embolic pulmonary hypertension]. AB - A 22-year old man with hydatid cyst of the right ventricle presented, for about 10 years, with clinical signs of post-embolic pulmonary hypertension. Despite tumoral resection, the patient died post-operatively of his pulmonary hypertension. Post-mortem examination showed a hydatid cyst on the main pulmonary artery and fixed post-embolic pulmonary hypertension, but we were unable to determine whether we were dealing with old migrated cysts or blood clot emboli developed in contact with the cardiac tumour. PMID- 3113386 TI - [Cardiobacterium hominis on a aortic valve prosthesis]. AB - A new case of late bacterial endocarditis caused by Cardiobacterium hominis is reported. The infection developed on an aortic valve prosthesis and responded favourably to medical treatment. The main characteristics of the micro-organism and of the oslerian graft are reviewed in the light of published data. The problem of endocarditis with negative blood cultures is discussed since C. hominis is reputed difficult to cultivate, although this was not the case in our patient. PMID- 3113388 TI - [Cardiac metastases. Clinical arguments of the diagnosis]. AB - The case reported here concerns an 80-year old man without history of coronary disease whose electrocardiogram showed localized and stable repolarization disorders, viz. elevated ST segment with isoelectric point J and negative T wave. This pattern suggested cardiac metastasis after chest examination had revealed a bronchial epidermoid carcinoma. Two-dimensional echocardiography showed that the lateral wall of the left ventricle was thickened, hyperechogenic and akinetic. The secondary cardiac lesions were confirmed at pathological examination. This case has prompted us to discuss the frequency of such secondary tumours of the heart, their mode of dissemination to the myocardium and their clinical and electrocardiographic aspects. It underlines the usefulness of echocardiography for the diagnosis of cardiac tumours. PMID- 3113389 TI - [Traumatic tricuspid insufficiency. Apropos of a case treated by conservative surgery]. AB - Traumatic tricuspid insufficiency is a rare condition which raises the problem of when and how should its surgical correction be performed. Its diagnosis has been considerably facilitated by echocardiography. We report a case of traumatic tricuspid insufficiency with extensive lesions of the tricuspid valve system, which was diagnosed after a 15-year period without functional signs. Echocardiography and Doppler ultrasounds provided very accurate information on the lesions. Optimal correction was obtained by conservative surgery. The excellent results observed at short and medium term suggest that surgical indications should be extended. PMID- 3113391 TI - [Biology and pathology of the heart and blood vessels. Study Group on Cardiovascular Research. Vittel, 6-7 mai 1987. Abstracts]. PMID- 3113390 TI - [Foreign body in the tricuspid valve with valvular insufficiency and right-left shunt]. AB - We present the case of a 50-year old man who progressively developed tricuspid valve insufficiency with opening of a patent foramen ovale responsible for right to-left shunt with polycythaemia. The tricuspid valve insufficiency was due to a foreign body, probably of surgical origin as suggested by its radiological image and by the patient's previous history. It would have been introduced, far away from the tricuspid valve (compound fracture of the wrist), several years previously. At surgery, we found the foreign body embedded in the valve system. As a possible mechanism for the mutilation, an undiagnosed endocarditis was suspected but could not be confirmed. Three cases tricuspid endocarditis (with foreign bodies in the right ventricle) and 3 cases of asymptomatic tricuspid valve foreign bodies have been published. Fifty-five cases of foreign bodies introduced peripherally and migrated into the heart, the pericardium and the pulmonary artery are reviewed. PMID- 3113393 TI - [Coronary risk factors. The French paradox]. AB - Concordant data suggest that the frequency of ischaemic heart diseases in France is relatively moderate and noticeably lower than in most industrial European or English-speaking countries. This fact is documented by mortality statistics and planned surveys (Parisian Prospective Study, Records, ENIM). This peculiarity does not seem to be ascribable to the level of the classical coronary risk factors in France. Thus, the incidence of ischaemic heart diseases observed in the Parisian Prospective Study is much lower than that of similar American studies, even after adjustment to risk factor levels. The dietary lipid intake of the French seems to be about the same as that of nationals of high coronary mortality countries. The French paradox lies in the contrast between a food rich in saturated fatty acids and a moderate coronary mortality rate, fairly similar to that observed in Mediterranean countries where the dietary fat intake is much smaller than in France. The high mean level of alcohol consumption in France might be one of the factors responsible for this French peculiarity. PMID- 3113392 TI - [Framingham 36 years later]. AB - Although cardiovascular mortality has decreased in recent years, it is still largely due to coronary disease: 1 out of 5 men and 1 out of 17 women are affected by that disease before the age of 60. Among the risk factors involved are lipid disturbances, themselves divided into three factors: LDL-cholesterol, triglycerides and HDL-cholesterol. A plasma LDL-cholesterol level above 150 units is a high risk factor. Triglyceride levels higher than 1.50 g/l, associated with HDL levels lower than 40 mg/dl constitute a new entity, a genetic disease associated with a special fragment on chromosome 11, characterized by high risk low HDL levels (below 40). Another risk factor, even in elderly people, is arterial hypertension. Cigarette smoking, lack of physical activity, diabetes and mental stress remain important factors, whereas obesity has become a separate factor. Finally, such factors as ECG abnormalities, plasma uric acide or plasminogen levels, familial context, etc., may be taken into consideration. All dietetic and therapeutic measures aimed at lowering the cholesterol level show a 2-3 p. 100 fall in the incidence of coronary disease for each 1 p. 100 reduction of blood cholesterol. A new programme, similar to those used in screening for high blood pressure subjects, will be set up in the U.S.A. to identify people with a blood cholesterol level higher than 2.40 g/l, treat them and bring that figure down below 2.00 g/l. The management of arterial hypertension is still based on treatments which do not increase blood cholesterol or increase HDL. They include alpha-blockers, beta-2 agonists and blockers of intracellular contractility. They have the additional advantage of improving capillary perfusion. PMID- 3113394 TI - [Prevention trials and role of vascular factors in moderate arterial hypertension]. AB - Epidemiological studies on the treatment of moderate arterial hypertension show little change in the frequency of coronary disease despite a significant lowering of arterial pressure. This phenomenon reflects the causative role played by alterations of the main arteries in the cardiovascular morbidity and mortality of treated hypertensive patients. These alterations may be of different natures, notably haemodynamic (increased arterial rigidity) or biochemical (especially changes in lipid profile). Seen from that angle, involvement of the main arteries reflects either an arterial wall pathology specific to the hypertensive disease, or an associated atherosclerosis, or the effect of certain drugs. The role of each of these factors is described. PMID- 3113395 TI - [The predictive value of apolipoproteins in atheroma]. AB - During the last three decades studies on the pathogenesis of atheroma have highlighted successively lipids, lipoproteins and apolipoproteins. The undisputed role of cholesterol has been widened by taking into account the nature and composition of lipoproteins in addition to their plasma levels. The concept of relative atherogenicity of lipoproteins and a better understanding of the role played by apolipoproteins have thrown more light on the formation of atheromatous plaques in the absence of hyperlipidaemia. On this point must be mentioned studies that associate LDL apo-B with coronary risk, and apo-A1 abnormalities which predispose to atheromatosis. More recently, attention has been focused on apo-E as a genetic factor that may interact with the environment to modulate blood cholesterol and triglyceride levels and secondarily influence individual tendencies to develop atherosclerosis. The three major forms of apo-E (E2, E3, E4) are encoded by three alleles (E2, E3, E4) and act on the same locus of chromosome 19 to determine 6 apo-E phenotypes in the population. We now know that the E2 allele is associated with lower levels, and the E4 allele with higher levels, of LDL-cholesterol than the E3 allele. E4 is a risk factor which predisposes to coronary atherosclerosis. It follows that the E2 allele should have protective powers, provided no other factor, ecological or hereditary, intervenes to foster the development of an atherogenic hypertriglyceridaemia. PMID- 3113396 TI - [Results of prevention trials by intervention with lipids]. AB - When only statistically comparable studies are taken into account, there are three primary prevention and eight secondary prevention studies. In 9 out these 11 studies the calculated decrease in the incidence of coronary disease are in favour of a beneficial effect of the lipid-lowering treatment. Some studies suggest that femoral atherosclerosis is receding and that coronary atherosclerosis is stable or progresses more slowly, but this always provided the plasma lipids are significantly and durably reduced. Subjects at high cardiovascular risk, therefore, must be treated, but one should now proceed even further, since the decrease of total cholesterol in the general population is paralleled by a decrease of coronary disease. This is in keeping with the results of extensive epidemiological surveys (notably the Framingham survey) which show that the lower the total cholesterol level the brighter the cardiovascular prognosis. PMID- 3113397 TI - [Puncture of peripheral veins in newborn infants and infants]. PMID- 3113398 TI - Effect of starvation, malnutrition, and trauma on the gastrointestinal tract flora and bacterial translocation. AB - We have previously shown, in an animal model, that viable indigenous bacteria will cross the intact gastrointestinal (GI) mucosa and spread systemically, a process termed bacterial translocation, if the normal bacterial ecology of the gut was sufficiently disrupted to allow bacterial overgrowth or if the animals were severely immunosuppressed. Starvation or protein malnutrition disrupts the normal indigenous GI tract microflora and impairs host antibacterial defenses. Consequently, we tested the effect of the combination of starvation or protein malnutrition plus burn trauma in promoting bacterial translocation from the GI tract. Bacterial translocation was measured by quantitatively culturing the mesenteric lymph nodes, spleens, livers, blood, and peritoneal cavities of normal or burned (30% of total body surface area) CD1 mice deprived of food for three days or fed a low-protein (0.03%) diet. The effect of starvation or protein malnutrition on the gut microflora was determined by quantitatively measuring the levels of bacteria present in the ceca. Both starvation and protein malnutrition increased the cecal levels of gram-negative enteric bacilli and decreased the levels of lactobacilli and strict anaerobes. Surprisingly, neither starvation nor protein malnutrition promoted bacterial translocation, even though these animals lost over 20% of their body weight and the ecology of the gut microflora was disrupted. In fact, the protein-malnourished animals exhibited lower incidences of bacterial translocation than normally nourished animals when both groups were monoassociated with Escherichia coli C-25 or monoassociated and burned. Thus, it appears that protein malnutrition does not promote bacterial translocation, even when combined with burn trauma. PMID- 3113399 TI - Do oxygen consumption and carbon dioxide production affect cardiac output after cardiopulmonary bypass? AB - This study examines the oxygen consumption (VO2) and carbon dioxide production (VCO2) occurring before, during, and after cardiopulmonary bypass (CPB) and whether they correlate with changes in cardiac output. Twenty-three patients undergoing open heart surgery were studied. Group 1 (N = 11) received fentanyl citrate, 50 micrograms/kg, intravenously during the induction of anesthesia. Group 2 (N = 12) received 100 micrograms/kg of fentanyl citrate intravenously. We measured VO2, VCO2, as well as hemodynamic and biochemical factors. Initial statistical analyses failed to show any differences in the VO2, VCO2, hemodynamic, or biochemical factors between groups 1 and 2. Therefore, the data from both groups were combined. In comparing the average (for all data) of the post-CPB with the pre-CPB periods in both groups for the metabolic factors, there were 9.0%, 11.5%, and 2.4% increases in the VO2, VCO2, and respiratory quotient, respectively. There was an 80% increase in total serum lactate levels seen in the post-CPB periods when compared with the pre-CPB periods. Serum triglyceride and free fatty acid levels measured in the post-CPB period decreased 39% and 25%, respectively, when compared with the pre-CPB periods. Although there were no changes in the cardiac outputs following CPB, the post-CPB periods showed a 37% increase in central venous pressure when compared with the pre-CPB periods. These data suggest that although there are significant metabolic and biochemical sequelae to CPB, the modest increases in post-CPB VO2, and VCO2 did not affect cardiac output following cardiovascular surgery. Increasing doses of narcotic do not have an effect on those relationships. PMID- 3113400 TI - The association of biliary and pancreatic anomalies with periampullary duodenal diverticula. Correlation with clinical presentations. AB - Fifty-eight symptomatic patients with periampullary duodenal diverticula (PDD) were examined for pancreatic and biliary anomalies using endoscopic retrograde cholangiopancreatography (ERCP), ultrasonography, and other imaging modalities. The pathologic findings in these patients were compared with those in a matched group of 58 patients without PDD, who were simultaneously undergoing a similar investigation for the same clinical presentations. Pathologic findings in the pancreas and/or biliary tree were detected in 70.7% of all patients with PDD, compared with 39.7% in the control group. In patients with PDD, pancreatobiliary anomalies were detected in all patients who presented with jaundice, 85% of patients with pancreatitis, and 27.8% of patients with abdominal pain, as compared with 60%, 40%, and 17%, respectively, in the control group. In 23 patients, ERCP findings demonstrated pancreatobiliary abnormalities that were not detected by other imaging modalities. Fifteen of the patients with PDD and pancreatobiliary anomalies had undergone cholecystectomy between six months and five years previously. We conclude that ERCP is essential in the investigation of all patients with PDD, especially those presenting with jaundice or pancreatitis. Biliary surgery in patients with PDD and a dilated bile duct should include a biliary drainage procedure to prevent recurrence of pancreatobiliary disease. PMID- 3113401 TI - No evidence for lysophospholipid formation during peroxidation of phospholipids by NADPH-cytochrome P-450 reductase and iron ions. AB - Liposomes comprised of liver microsomal phospholipids and radioactive phosphatidylcholine or phosphatidylethanolamine as tracers were incubated with isolated liver microsomal NADPH-cytochrome P-450 reductase, NADPH and ADP-EDTA chelated iron ions, a system which stimulates peroxidation of unsaturated fatty acids of phospholipids. Phospholipids and their reaction products were extracted and chromatographed on HPLC. Phosphatidylcholine and phosphatidylethanolamine considerably decreased after 30 min incubation, depending on the enzyme and NADPH as measured by UV absorbance and radioactivity. However, neither a lysophospholipid peak nor a lysophospholipid-like peak were detectable. We suggest that lysophospholipid formation during microsomal lipid peroxidation is exclusively due to phospholipase A2 and not due to peroxidative breakdown of the unsaturated fatty acid in the beta-position of glycerol. PMID- 3113402 TI - Characterization of hepatic and pulmonary cytochromes P-450 in 3 methylcholanthrene-treated hamsters. AB - Two major forms of hepatic cytochrome P-450 (hepatic P-450MCI and P-450MCII) were purified approximately 5-fold from liver microsomes in Syrian golden hamsters treated with 3-methylcholanthrene (MC). The purified preparations of hepatic P 450MCI and P-450MCII contained 9.6 and 8.3 nmol cytochrome P-450 (P-450) per mg protein, respectively, and were essentially free from NADPH-cytochrome c (P-450) reductase (fpT), NADH-cytochrome b5 reductase and cytochrome b5. By sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the molecular weights of hepatic P-450MCI and P-450MCII were estimated to be 56,000 and 53,500. Further, a major form of pulmonary P-450 (P-450MC) were purified from lung microsomes of MC-treated hamster, and contained 14.2 nmol P-450 per mg protein, and estimated to be 56,000 in monomeric molecular weight, indicating the similar molecular weight to hepatic P-450MCI in the hamster. From the absorption spectra the oxidized forms of hepatic P-450MCI and P-450MCII were high- and low-spin ferric hemoproteins, respectively, and pulmonary P-450MC was similar to hepatic P 450MCII in their hemoprotein spin state. No difference, however, was observed in the CO-reduced forms among hepatic P-450MCI, P-450MCII and pulmonary P-450MC, all exhibiting 446.5 nm Soret bands. In a reconstituted system containing fpT and dilauroylphosphatidylcholine (DLPC), pulmonary P-450MC efficiently catalyzed benzo[a]pyrene (BP) hydroxylation at a rate of 11.4 mol formed per min per mol P 450, but hepatic P-450MCI and P-450MCII both exhibited lower levels, e.g., 0.49 and 0.54, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113403 TI - Effects of dietary fat and aflatoxin B1 on microsomal monooxygenase activity. AB - An acute experiment was conducted to determine the short-term effect of an LD50 dose of AFB1 on rats fed a diet containing either 30% corn oil (unsaturated) or 28% beef fat (saturated) for 3 weeks. The male weanling Wistar rats weighing 50 65 g were fed the respective dietary fats for 2 weeks and then given a single dose of AFB1 (7 mg/kg body weight) dissolved in dimethyl sulfoxide by gastric intubation. One week later they were sacrificed and assays for p-nitroanisole demethylase and benzpyrene hydroxylase were performed on liver microsomes to determine the activity associated with the two types of dietary fat. The rats fed corn oil or unsaturated fat had lower total liver fat and a lower mortality rate than those fed beef fat. The basal levels of liver microsomal oxidase activity were higher in rats fed the corn oil diet than in those given the beef fat diet. PMID- 3113404 TI - The 14CO2 breath test: facilities and limitations of a rapid and noninvasive method for in vivo evaluation of modified hepatic cytochrome P-450--a critique. AB - By means of the breath test technique the cascade from O-demethylations to CO2 was investigated after pretreatment of mice with warfarin, phenobarbital, cobaltous chloride, sodium vanadate and metyrapone. It was the intention to examine the validity of the technique with respect to cytochrome P-450 activity. Therefore three different radioactive labeled substrates, i.e., hydrogen carbonate, formate and xenobiotics, were applied at three different levels of the one-carbon pathway and were utilized to demonstrate possible interference of the modifiers with the sequence from O-demethylation to CO2. Real in vivo information about a modified cytochrome P-450 system can be obtained using model substrates carefully selected with regard to the type of expected modification of the monooxygenase system. In addition, a parallel monitoring of the consecutive reaction sequence by measuring the conversion of formate to CO2 is necessary in order to guarantee the validity of the in vivo technique in visualizing the activity of the hepatic monooxygenase system. PMID- 3113405 TI - [Distribution of lipoproteins in the human aorta wall]. AB - Localization of lipoproteins of high, low and very low density in the wall of human aorta was studied by an indirect immunofluorescence technique using antibodies to apoproteins (apo) A-I, B-100 and C-III. Apo A-I and apo C-III were distributed relatively evenly through the thickness of the vessel without visible damage, with some prevalence in the zone of lipid infiltration. Apo B-100 were revealed in significant amount in the intima if their content in the aortic media was low. The content of apo A-I and apo C-III was somewhat increased in the lipid strip. Massive deposits of apo B-100 which were frequently distributed unevenly were found in the fibrous plaque. Pretreatment of nonfixed cryostat sections with saline solution containing bovine serum albumin produced a diffused decrease in the intensity of specific fluorescence this being due to the release of lipoproteins from the tissues. The mechanism of the low density proteins accumulation in the aorta, their binding to the vascular wall components is discussed. PMID- 3113406 TI - Massive hollow fiber clotting: a distinct problem in treatment of cryoglobulinemia by membrane plasmapheresis. AB - Two patients with cryoglobulinemia were treated with plasmapheresis in combination with immunosuppressive therapy. One had Waldenstrom's macroglobulinemia, and the other suffered from systemic lupus erythematosus. Membrane plasmapheresis, using membrane plasma separators, was performed, and the initial plasmapheresis treatments were unsatisfactory because of clotting of hollow fibers by cryoglobulin. The plasma filtration rate and the clearance of immunoglobulins fell rapidly with the clotting of the hollow fibers. This technical difficulty was overcome by prediluting the blood with normal saline before passing it through the membrane plasma separator. The mechanism of preventing clotting of hollow fiber by saline predilution is likely to be the reduction of serum viscosity and the lowering of cryoglobulin concentration. This modification is simple and efficient and enables membrane plasmapheresis to be performed effectively in patients with cryoglobulinemia without complicated and expensive machines. PMID- 3113408 TI - Litigation, quality and use of health services: international lessons from a uniquely American phenomenon. PMID- 3113407 TI - An immunohistochemical and electron microscopic study of a central venous hemangioma of the mandible. AB - To date, 96 cases of central hemangiomas of the jawbones have been described in the literature. Of these cases, the mandible has been more affected than the maxilla, while approximately 50% of all cases occur in the first and second decades of life. Histopathologically, cavernous and capillary types are often found, in contrast to the central venous type, which is rare. We have recently treated a 44-year-old man, who was found to have a central venous hemangioma in his mandible. Immunohistochemical studies were performed using factor-VIII related antigen as well as various lectins as markers for tumor endothelial cells. Our results showed that four kinds of lectins (UEA-I, PNA, ConA, and DBA) were useful for the marker as factor-VIII-related antigen. Scanning electron microscopic findings of this tumor demonstrated that the lumina of the blood vessels were more rough, while the lining endothelial cells were more irregular when compared with those of the normal vascular system. PMID- 3113409 TI - Histological changes following transplantation of developing teeth to more advanced functional positions. PMID- 3113410 TI - Resolution of acromegaly after removal of a bronchial carcinoid shown to secrete growth hormone releasing factor. AB - A 29 year old woman with an enlarged pituitary fossa and classical acromegaly, possibly present for ten years, had biochemical and partial somatic resolution of the disorder after removal of a bronchial carcinoid tumour. In addition, galactorrhea stopped, menstruation returned after two years, and amenorrhea and elevated prolactin levels fell towards normal. Immunocytochemistry showed numerous growth hormone releasing factor (GRF) staining cells in the tumour. The tumour cells, when cultured, produced a supernatant selectivity stimulating human pituitary somatotrophic cell cultures to produce growth hormone (GH). The bronchial carcinoid did not secrete detectable GH, but extracts of it, and preoperative serum contained GRF immunoreactivity which coeluted with synthetic human pancreatic GRF. PMID- 3113411 TI - Nutritional status on admission to a general surgical ward in a Sydney hospital. AB - To assess the nutritional status of patients on admission to a general surgical ward in a major teaching hospital in Sydney, we examined 84 men and women. We measured, recorded, and/or calculated: history of weight loss, body mass index (BMI), triceps skinfold, arm muscle circumference, hemoglobin, total lymphocyte count, and plasma albumin level. Measurements were graded normal, borderline, or abnormal and patients were considered malnourished if they had two or more abnormal measurements, three or more borderline measurements, or one abnormal and two borderline measurements. Thirty-one patients (37%) were found to have one or more measurements below the reference range. Twelve patients (14%) were considered malnourished and of this group more than half were of normal weight or overweight. But if indices of overnutrition are included in a definition of malnutrition then a high BMI was the most common abnormal index of nutritional status. Forty-six patients (55%) had a BMI of greater than 25, that is, were overweight. This single study showed a higher percentage of overnutrition amongst hospital patients than previous work has indicated and secondly that malnourished patients are not necessarily underweight. PMID- 3113412 TI - Thrombolytic therapy. PMID- 3113413 TI - Fat emulsion adversely affects lymphocyte reactivity. AB - Although nutritional repletion of malnourished individuals may improve tests of cell-mediated immunity, the effects of intravenous nutrient solutions themselves on the immune system are largely unknown. This study examined the effects of five parenteral nutrition solutions on in vitro lymphocyte reactivity and measured lymphocyte responsiveness in patients receiving parenteral nutrition. Normal human lymphocytes were incubated with dilutions of an amino acid/dextrose solution, an amino acid/dextrose/fat solution, an amino acid solution, dextrose, and a fat emulsion, and lymphocyte responsiveness to antigenic (PPD) and mitogenic (PHA) stimulation was measured using an in vitro electrophoretic test of cell-mediated immunity. Lymphocyte reactivity was measured in 15 postoperative patients allocated randomly to receive either simple electrolyte solutions or isocaloric parenteral regimes with or without a fat emulsion. In vitro lymphocyte responses were significantly depressed (P less than 0.001) by the fat emulsion at concentrations similar to those achieved in clinical practice but were unaffected by dextrose or amino acid solutions. Lymphocyte reactivity was significantly depressed in patients during infusion of the fat emulsion in comparison with controls (P less than 0.05). The results show that fat emulsion impairs lymphocyte reactivity and suggest that careful consideration should be given before using fat emulsions in patients in whom cell-mediated immunity is impaired already. PMID- 3113414 TI - Traumatic oesophageal pseudodiverticulum. AB - Dissection of the posterior pharyngeal wall and oesophagus due to trauma has a clinical presentation similar to that of oesophageal atresia with or without tracheo-oesophageal fistula. It is important to establish the diagnosis in order to prevent unnecessary surgery. PMID- 3113415 TI - Postpartum spinal wedge fractures in a 27-year-old epileptic anorectic woman. PMID- 3113416 TI - The effects of head-down tilt on carotid blood flow and pulmonary gas exchange. AB - Common carotid artery blood flow (CCF), pulmonary gas exchange and ventilation were measured in six subjects in the supine posture (SUP I), serially during 20 min of head-down tilt at -30 degrees (HDT) and after returning to the supine posture (SUP II). CCF was approximately 6% lower during HDT, with a transient increase during the second minute, and was about 7% higher during SUP II than during SUP I. The transition from SUP I to HDT caused increases in O2 uptake (VO2), CO2 output, respiratory exchange ratio and tidal volume in the first minute. Similar responses were apparent following the HDT to SUP II transition, except for VO2, which changed little. Correction of VO2 for changes in estimated lung O2 stores indicated that about 200 ml of blood were shifted within the circulation by the tilt transitions which provided a ventilatory stimulus. HDT can cause a loss in blood and tissue O2 stores and gain in CO2 stores by shifting blood volume toward and blood flow away from the dependent headward vascular compartment and perhaps by producing ischemia in the elevated lower extremities. Cerebral venous congestion during HDT appears to cause periodic breathing and reduce CCF, the latter being partially offset by reduced flow resistance in the carotid artery. PMID- 3113417 TI - Chemical selection for beta-galactosidase activity in Drosophila melanogaster. PMID- 3113418 TI - Mechanism of suppression in Drosophila: regulation of tryptophan oxygenase by the su(s)+ allele. AB - The suppressor gene, su(s)2, in Drosophila melanogaster restores the production of red and brown eye pigments for some purple and vermilion mutant alleles, respectively. We showed previously that the product of the su(s)+ allele caused inhibition of the sepiapterin synthase A produced by the purple mutant but did not affect the wild-type enzyme. Suppression was accomplished by removing su(s)+ from the genome. We now report that the tryptophan oxygenase, produced by suppressible vermilion alleles, is also inhibited by extracts from su(s)+ flies. The inhibition of the vermilion enzyme can be reduced or eliminated, respectively, by prior storage of the extract at 4 or -20 degrees C or by boiling, whereas the wild-type enzyme is not affected by extracts of su(s)+ flies. Also, when the suppressible vermilion strain is raised on certain diets, brown eye pigment production occurs. This epigenetic suppression was reduced by the presence of an extra copy of su(s)+ in the genome. These data support a posttranslational mechanism for regulation of enzyme activity in which the activity of the mutant enzyme is reduced by the product of the su(s)+ allele. How the su(s)+ gene product can distinguish between the normal and the mutant forms of these two enzymes is discussed, along with other mechanisms for suppression that are currently under investigation. PMID- 3113419 TI - Brain protein 4.1 subtypes: a working hypothesis. PMID- 3113420 TI - Molecular cloning of cDNA for human poly(ADP-ribose) polymerase and expression of its gene during HL-60 cell differentiation. AB - Human placental poly(ADP-ribose) polymerase was purified and the NH2-terminal amino acid sequences of 16 KDa and 40 KDa chymotryptic peptides were determined. Screening of a lambda gt11 cDNA library of normal human placenta with a 51-mer oligodeoxyribonucleotide yielded one clone with a 1.8 Kb insert and two clones with 2.1 Kb inserts. The amino acid sequence deduced from the nucleotide sequence of the 1.8 Kb insert exactly matched the determined amino acid sequences. From a Northern blot analysis, a single 3.6 Kb mRNA was detected in HL-60 cells. Furthermore, the RNA expression of the poly(ADP-ribose) polymerase gene was shown to decrease during the granulocytic differentiation of HL-60 cells upon induction by retinoic acid. PMID- 3113421 TI - Substitution of an arginyl residue for the active site lysyl residue (Lys258) of aspartate aminotransferase. AB - The active site lysyl residue (Lys258) of E. coli aspartate amino transferase was substituted for an arginyl residue by oligonucleotide-directed, site-specific mutagenesis. The mutant enzyme was obviously unable to form an aldimine bond with pyridoxal 5'-phosphate but firmly bound the coenzyme. The finding that the mutation did not lead to entire loss in the enzymic activity suggests that Lys258 may not be essential but auxiliary for enzymic catalysis. It is also conceived that the positive charge provided by Arg258 may contribute to the enzymic catalysis. PMID- 3113422 TI - 13-Hydroxyoctadecadienoic acid (13-HODE) stimulates prostacyclin production by endothelial cells. AB - The effect of 13-hydroxyoctadecadienoic acid (13-HODE), an endogenous lipoxygenase metabolite of linoleic acid, on prostacyclin production by fetal bovine aortic endothelial cells was evaluated. Time-dependent release of radioimmunoassayable 6KPGF1 alpha in the presence of 13-HODE (10 uM) was stimulated by 39%, 27%, and 34% at 10, 30 and 120 min respectively. 13-HODE (10 uM) had no effect on the conversion of exogenous [14C] arachidonic acid (AA) to prostacyclin. When the effect on AA release was evaluated in [14C] AA prelabeled cells, 13-HODE (10nM) stimulated the release of AA from membrane phospholipids. Analysis of cellular phospholipids revealed a significant decrease in phosphatidylethanolamine. Our results demonstrate that 13-HODE stimulates prostacyclin production by enhancing AA release from phospholipids. PMID- 3113423 TI - Specific interaction of vinculin with alpha-actinin. AB - Vinculin and alpha-actinin are cytoskeletal proteins present at focal contacts of the ventral surface of cultured fibroblasts. We labelled alpha-actinin with an acceptor fluorophore and vinculin with a donor. A mixture of vinculin and alpha actinin showed a 28% quench, due to energy transfer, suggesting an interaction. Quench of vinculin was dependent on the concentration of alpha-actinin; Scatchard analysis gives a dissociation constant in the microM range. Quench was inhibited by excess unlabelled alpha-actinin, and by reaction of the acceptor protein with p-chloromercuribenzoate. We found that vinculin had a slightly greater elution volume in a gel filtration column equilibrated with alpha-actinin, indicating a higher effective Stokes radius due to the interaction of the two proteins. PMID- 3113424 TI - Prostaglandin synthesis and membrane fatty acid composition in the heart of obese Zucker rats. AB - Genetically obese Zucker rats share several abnormalities with obese patients: inheritance of the obesity, hyperinsulinemia, hypertriglyceridemia. Because alterations in membrane fatty acid composition and in prostaglandin synthesis can be involved in the genesis of the cardiovascular complications of obesity, cardiac prostaglandins and phospholipid fatty acid composition were compared in obese and lean animals. Obese cardiac tissues produced smaller amounts of prostacyclin, thromboxane A2 and PGE2 than lean (p less than 0.01). The cyclooxygenase pathway and the activation of phospholipase by the calcium ionophore A 23187 were not altered. Phospholipid fatty acid composition of obese tissues was abnormal: the amount of stearic, arachidonic, docosapentaenoic and cervonic acids was decreased, whereas the amount of linoleic acid, the precursor of arachidonic acid, was doubled. It is concluded that obesity in Zucker rats is associated with alteration of cardiac arachidonic acid metabolism and that the alterations associated with obesity can be studied in this rat strain. PMID- 3113425 TI - Stimulations of arachidonate release and inositol-1,4,5-triphosphate formation are mediated by distinct G-proteins in human platelets. AB - Addition of fluoroaluminate to human platelet suspension stimulated thromboxane synthesis and inositol-1,4,5-triphosphate formation in a time and dose dependent manner. Neomycin inhibited markedly fluoroaluminate induced inositol-1,4,5 triphosphate formation without significantly affecting thromboxane synthesis. Preincubation of platelets with PGE1, also inhibited significantly inositol-1,4,5 triphosphate formation with modest reduction of thromboxane synthesis. On the contrary, pretreatment of platelets with pertussis toxin inhibited fluoroaluminate stimulated thromboxane synthesis without affecting inositol-1,4,5 triphosphate formation. Similarly, preincubation of platelets with phorbol ester, PMA, inhibited markedly thromboxane synthesis with modest reduction of inositol 1,4,5-triphosphate formation. These results indicate that inositol-1,4,5 triphosphate formation and arachidonate release and thromboxane synthesis are controlled separately and are mediated by different G-proteins which are coupled to phospholipase C and phospholipase A2 respectively in platelets. PMID- 3113426 TI - Neomycin is a potent agent for arachidonic acid release in human platelets. AB - Neomycin (10 microM - 1 mM) was found to induce considerable release of [3H]arachidonic acid from phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine in saponin-permeabilized human platelets prelabeled with [3H]arachidonic acid. The magnitude of arachidonate liberation was almost equal to that induced by A23187 (400 nM) or even greater than that caused by thrombin (1 U/ml). Moreover, neomycin enhanced arachidonic acid release induced by thrombin. Since no significant formation of diacylglycerol and phosphatidic acid via phospholipase C was observed, the arachidonate liberation was considered to be mainly catalyzed by phospholipase A2 action. Addition of neomycin (100 microM) to 45Ca2+-preloaded platelets elicited 45Ca2+ mobilization from intracellular stores. These results indicate evidence that neomycin evokes Ca2+ mobilization from internal stores, which leads to activation of phospholipase A2 to release arachidonic acid in human platelets. PMID- 3113427 TI - Stimulation by GTP-binding proteins (Gi, Go) of partially purified phospholipase C activity from human platelet membranes. AB - A phospholipase C exhibiting preferential hydrolytic activity for polyphosphoinositides was partially purified from the deoxycholate extract of human platelet membranes by Q-Sepharose and Heparin-Sepharose column chromatographies. The activity of this purified phospholipase C free of the GTP gamma S-binding activity was stimulated at a similar level by addition of purified rat brain Gi or Go. These results suggest that GTP-binding proteins may interact directly with a solubilized membrane phospholipase C to stimulate its activity. PMID- 3113428 TI - A pertussis/cholera toxin sensitive G-protein may mediate vasopressin-induced inositol phosphate formation in smooth muscle cell. AB - Arg-vasopressin (AVP) stimulates the production of inositol-1,4,5-triphosphate, inositol-1,4-bisphosphate and inositol-1-phosphate in A10 smooth muscle cell line. The AVP stimulation is rapid, time and dose dependent with an ED50 value of 5 nM. Protein kinase C activator, phorbol ester blocks the AVP effect on the production of inositol phosphates, suggesting that AVP induced phospholipase C (PLC) activation is under the negative feedback regulation by diacylglycerol production. Prolonged overnight treatment with either pertussis toxin and cholera toxin resulted partial inhibition of AVP-induced production of inositol phosphates. This result suggests that a novel G-protein similar to transducin might be involved in the AVP-induced PLC activation. PMID- 3113429 TI - Hydroxylamine-stable covalent linkage of myristic acid in G0 alpha, a guanine nucleotide-binding protein of bovine brain. AB - G0 alpha, a guanine nucleotide-binding protein with a strong homology to the G1 alpha and Gs alpha regulatory proteins of adenylate cyclase, is shown to contain myristic acid. The attachment of myristate to the protein is stable to hydroxylamine treatment, and since the amino-terminal sequence of G0 alpha is typical of proteins with amino-terminal myristate, the inference is strong that G0 alpha is also myristylated at its amino-terminal glycine. PMID- 3113430 TI - Up and down regulation of serine esterase release from mouse cytotoxic T lymphocytes by tumor-promoting phorbol ester. AB - Activation of mouse cytotoxic T lymphocytes (CTL) with target cells expressing antigen resulted in the release of serine esterase (SE) into the culture supernatant. Short term treatment (3 hr) of CTL with phorbol-12-myristate-13 acetate (PMA) plus ionophore also caused stimulation of SE release from CTL, while neither PMA alone or ionophore alone could induce SE release. In contrast to this, long term treatment (24 hrs) of CTL with PMA resulted in the inability of CTL to release SE in respond to antigen or PMA plus ionophore. It was also demonstrated that protein kinase C activity of CTL disappeared during induction of desensitization of CTL by PMA. PMID- 3113431 TI - Reversible activation of NADPH oxidase in membranes of HL-60 human leukemic cells. AB - NADPH oxidase in membranes of undifferentiated and dimethylsulphoxide differentiated HL-60 cells was activated by arachidonic acid (AA) in the presence of Mg2+ and a cytosolic cofactor (CF) found in differentiated HL-60 cells. Basal superoxide (O2-) formation was enhanced several-fold by addition of the stable GTP-analogue, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), prior to AA and was completely prevented by that of GDP. Basal and GTP gamma S-stimulated O2- formation was terminated by GDP. In the presence of Mg2+ or EDTA, basal O2- formation ceased after 25 or 10 min, respectively, and was reinitiated by GTP gamma S or GTP gamma S plus Mg2+. Albumin terminated O2- formation, which was reactivated by AA in the presence of GTP gamma S. Our results show that (1) activation of NADPH oxidase in HL-60 membranes is dependent on endogenous GTP, Mg2+, AA and CF, which is induced during myeloid differentiation, and that (2) NADPH oxidase activation is a reversible process modulated by exogenous guanine nucleotides at various stages of activity of NADPH oxidase. We suggest crucial roles of guanine nucleotide-binding proteins in the activation, deactivation and reactivation of the enzyme. PMID- 3113432 TI - Evidence for cytochrome P450-mediated oxidation of uroporphyrinogen by cell-free liver extracts from chick embryos treated with 3-methylcholanthrene. AB - Cell-free preparations from liver of chick embryo treated with 3 methylcholanthrene catalyzed oxidation of uroporphyrinogen I in the presence of NADPH and 3,4,3',4'-tetrachlorobiphenyl. Extracts of untreated embryo liver or liver from embryo treated with glutethimide, a phenobarbital-like inducer of cytochrome P450 in this system, did not catalyse the oxidation. Direct involvement of cytochrome P450 was demonstrated by inhibition of the oxidation by CO, piperonyl butoxide and specific antisera to the methylcholanthrene-induced cytochrome P450. 2,4,2',4'-tetrachlorobiphenyl was inactive in the oxidation. These results may explain the role of induced cytochrome P450 in experimental uroporphyria. The oxidation may be useful as a simple assay for reactive O2 species. PMID- 3113433 TI - Stimulation of FSH release by erythroid differentiation factor (EDF). AB - The action of erythroid differentiation factor (EDF) on primary culture of rat anterior pituitary cells was examined. EDF stimulates FSH secretion in a dose dependent manner but not of LH secretion. ED50 of EDF for FSH secretion was 5 X 10(-10) M, while ED50 of LHRH for FSH secretion was 5 X 10(-9) M. These data indicate that EDF is a potent agonist for FSH secretion and the biological activity of EDF on anterior pituitary seems to be identical as that of FSH releasing protein (FRP). PMID- 3113434 TI - Light induces a rapid and transient increase in inositol-trisphosphate in toad rod outer segments. AB - The sub-second time course of changes in the content of [3H]inositol-1,4,5 trisphosphate was determined in rod outer segments from very rapidly frozen Bufo retinas that had been incubated with [3H]inositol. Rod outer segments were cut off frozen specimens with a cryostat microtome and the water soluble extracts were analyzed. The content of [3H]inositol-1,4,5-trisphosphate rose after approximately 250 msec of bright illumination, but returned to the unstimulated level after 1 sec, whether the stimulus remained on or not. That is, there was rapid but transient change in the content of [3H]inositol-1,4,5-trisphosphate after the onset of stimulation. PMID- 3113435 TI - Effects of bovine inhibin, transforming growth factor-beta and bovine Activin-A on granulosa cell differentiation. AB - To determine whether inhibin and its related peptides might act locally to control granulosa cell function and differentiation, the dose- and time-dependent effects of bovine inhibin, the homo-dimer of the beta-chain of bovine inhibin (Activin-A) and porcine TGF beta on rat granulosa cell aromatase activity and progesterone synthesis were investigated in vitro. TGF beta enhanced FSH-induced aromatase activity and progesterone synthesis, and accelerated the peak response for progesterone synthesis. Activin-A on the other hand, augmented FSH-induced aromatase activity while arresting progesterone synthesis, and anti-luteinization effect. By contrast, exogenous inhibin had no detectable effect on the steroidogenic potential of these cells. Thus TGF beta and Activin, unlike their similar effects on the release of FSH by the pituitary, appear to affect ovarian granulosa cell function in different fashion, under conditions where inhibin itself has no effect. PMID- 3113436 TI - The induction of IFN-gamma production and m-RNAs of interleukin 2 and IFN-gamma by phorbol esters and a calcium ionophore. AB - Human peripheral blood mononuclear leukocytes were found to produce large amounts of interferon-gamma in response to the calcium ionophore A23187 combined with the phorbol ester mezerein. This effect was synergistic since A23187 and mezerein separately did not induce significant interferon-gamma levels. A23187 plus mezerein induced high levels of interleukin-2 and interferon-gamma mRNAs. The presence of cyclohexamide, which inhibits protein synthesis by greater than 99%, had no effect on the induction by A23187 plus mezerein of mRNA from either gene, indicating that synthesis of proteins such as interleukin-2 is not required for activation of either gene. In addition, using different protocols of stimulation of lymphocytes it was shown that both interleukin-2 and interferon-gamma mRNA steady state levels varied in concert. We conclude that interferon-gamma and interleukin-2 genes are coordinately expressed and activation of transcription of these genes is a primary event of T cell activation independent of production of other proteins. PMID- 3113437 TI - Role of protein kinase C in luteinizing hormone-releasing hormone (LHRH) stimulated progesterone production in rat granulosa cells. AB - Treatment of rat granulosa cells with LHRH or the phorbol ester TPA stimulated progesterone (P) production during a 5-h incubation. The concomitant presence of a potent inhibitor of protein kinase C attenuated the LHRH effect by ca. 60% and completely blocked the stimulatory effect of TPA. Addition of TPA (10(-9), 10(-8) or 10(-7) M) or dioctanylglycerol (100 micrograms/ml) increased P production; these stimulatory effects were not potentiated by the concomitant presence of a calcium ionophore (A23187, 10(-7) or 10(-6)M). These data support the hypothesis that protein kinase C activation have a role in the steroidogenic action of LHRH in the ovary. PMID- 3113438 TI - Immunochemical study of role of chargerin II, a product of URFA6L of mitochondrial DNA in energy transduction of rat liver mitochondria. AB - Antibody against chargerin II [product of the unidentified reading frame A6L (URFA6L) of mitochondrial DNA] inhibited the ATP-Pi exchange reaction and reversed electron flow from succinate to NAD in mitoplasts (inner membrane plus matrix). The antibody against chargerin II caused greater inhibition on incubation with mitoplasts in the energized than the nonenergized state, suggesting that redox reactions are coupled with a conformational change of chargerin II. The present findings showed that chargerin II, the URFA6L product, may have a key role in energy transduction of mitochondrial oxidative phosphorylation. PMID- 3113440 TI - Combined pure red cell aplasia and primary autoimmune hypothyroidism in systemic lupus erythematosus. PMID- 3113439 TI - Ovarian renin gene expression is regulated by follicle-stimulating hormone. AB - The regulation of renin and renin messenger RNA (mRNA) in the rat ovary was examined to test the hypothesis that the expression of renin gene and the secretion of renin in the ovary is the estrogen-mediated process that responds to follicle-stimulating hormone (FSH). In the ovary of the immature 25-day female rats, the concentration of renin mRNA was comparatively low, but 36 h after injection of FSH, the renin mRNA content showed a three-fold increase compared to the basal level. This increase was consistent with the stimulation of the total renin concentration in the ovary. On the other hand, the total renin concentration in the rat uterus gradually decreased, suggesting that the enhancement of the contents of renin and renin mRNA by FSH is an ovary-specific phenomenon. In hypophysectomized rats, the total renin concentration in the rat ovary was stimulated by the estrogen as well as FSH. These findings suggest that the production of ovarian renin is regulated by the pituitary hormone, particularly FSH. PMID- 3113441 TI - [Effects of benzydamine on leukocyte aggregation]. AB - The effect of benzydamine (Tantum) on the aggregation of rat leukocytes was compared to some commonly used nonsteroidal antiinflammatory drugs (NSAID). The aggregation response was induced by various activators such as the tumour promoter phorbol myristate acetate, the chemotactic peptide N-formyl-methionyl leucyl-phenylalanine (FMLP), arachidonic acid, sodium arachidonate, platelet activating factor (PAF) and a combination of cytochalasin B and Ca++-ionophore A 23187. As compared to indomethacin, piroxicam and acetylsalicylic acid benzydamine was inhibitory against most of the activators, i.e. the receptor mediated induction of the aggregation by FMLP, the phorbol ester and sodium arachidonate. No effect could be observed against PAF induced aggregation. Under the assay conditions benzydamine exerted cytolytic effects at 2 X 10(-4) mol/l. Cytolysis reached 100% at 5 X 10(-4) mol/l benzydamine, as could be shown microscopically and by measurement of free cytosolic lactate dehydrogenase. Thus benzydamine exerted a broad spectrum inhibitory activity against rat leukocyte aggregation, possibly explained by its unspecific membrane affinity. PMID- 3113442 TI - Comparison of prostaglandin synthesis by endothelial cells from blood vessels originating in the rat, baboon, calf and human. AB - The synthesis of prostaglandins (PGs) was determined in endothelial cells obtained from various vessels from baboon, human and rat both by radioimmunoassay and prelabel of the cells with [3H] arachidonate. Cells were stimulated with bradykinin, ionophore A23187 or 10 microM arachidonate. Although prostacyclin (PGI2) has proven to be the major prostaglandin product of human umbilical vein and calf pulmonary artery endothelial cells, our results show that PGI2 is frequently not the major prostaglandin product of endothelial cells from other vessels. For example baboon endothelial cells lining the large vessels, aorta and cephalic vein produce mainly PGF2a with only small amounts of PGE2 and PGI2. Human endothelial cells from saphenous vein also produce mainly PGF2a. Baboon, human and rat adipose capillary endothelial cells make predominantly PGE2 and PGI2 with rat making significant amounts of PGF2a in addition. Endothelial cells from the rat aorta produced predominantly prostacyclin. PMID- 3113443 TI - Sensitivity difference to hepatotoxicity of cocaine in spontaneously hypertensive and Wistar Kyoto rats. AB - Experiments were conducted to determine the hepatic damage of cocaine in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats in terms of serum glutamic-oxaloacetic transaminase (SGOT) activity, liver weight/body weight ratio and hepatic microsomal enzyme activity, i.e., N demethylase activity or UDP-glucuronyltransferase (GT) activity. In subacute experiments, 2, 4 and 10 daily cocaine treatments elevated the level of SGOT activity and reduced the liver weight/body weight ratio in SHR rats. The ethylmorphine N-demethylase activity and the cocaine N-demethylase activity in SHR rats were significantly greater (31% and 26%, respectively) than those in WKY rats. Ten daily treatments with cocaine diminished the ethyl morphine N demethylase activity and the cocaine N-demethylase activity in SHR and WKY rats. However, attenuation of 4-nitrophenol GT activity was only observed in SHR rats. In acute experiments, a single dose of cocaine, 40 mg/kg, elevated the SGOT activity in SHR rats and reduced the 4-nitrophenol GT activity in SHR rats, but it did not affect the activities of SGOT and 4-nitrophenol GT in WKY rats. A higher dose of cocaine, 60 mg/kg, elevated the SGOT activity and reduced cocaine N-demethylase activity and 4-nitrophenol GT activity in both SHR and WKY rats. The present studies suggest that N-demethylation of cocaine plays an important role in the hepatotoxicity of cocaine in animals. PMID- 3113444 TI - Build-up and release from proactive interference during chronic ethanol consumption in mice: a behavioral and neuroanatomical study. AB - Male mice of the BALB/c strain were given a solution of 15% ethanol as their only source of fluid during either 24 or 48 weeks. They were submitted to a sequential alternation (SA) task in a T-maze (6 successive trials). It was found that 48 but not 24 weeks of alcohol administration lead to a deficit as compared to pair-fed or tap-water controls. Whereas experimental mice performed as well as controls on the first 3 choices, they exhibited a gradual decrease in the SA rate on subsequent trials. We suggest that this deficit might result from an exaggerated vulnerability to proactive interference (PI). In order to further test this hypothesis, a second experiment investigated whether a between-trials variation of context of the maze would increase performance. It was found that the SA rate improved as soon as the variation was provided (5th trial). We suggest that the deficit of experimental mice results from an impairment of retrieval processes. A neuroanatomical study was conducted to quantify cell losses resulting from 8, 24 or 48 weeks of ethanol treatment in the mammillary bodies (MM) or the hippocampus (HPC). At the time of appearance of the deficit, MM exhibited a -32% cellular loss, whereas this was only -18% in the HPC. This result emphasises the importance of MM lesion in memory deficits resulting from long-term alcohol consumption. PMID- 3113445 TI - Oligosialogangliosides inhibit GM2- and GD3-synthesis in isolated Golgi vesicles from rat liver. AB - The effect of end-product gangliosides (GD1a, GT1b, GQ1b) on the activities of two key enzymes in ganglioside biosynthesis, namely GM2-synthase and GD3-synthase in rat liver Golgi apparatus, has been investigated in detergent-free as well as in detergent-containing assays. In detergent-free intact Golgi vesicles, phosphatidylglycerol was used as a stimulant. This phospholipid was earlier shown to stimulate the activity of GM2-synthase without disrupting the vesicular intactness; it has, however, no effect on GD3-synthase (Yusuf, H.K.M., Pohlentz, G., Schwarzmann, G. & Sandhoff, K. (1983) Eur. J. Biochem. 134, 47-54). In the presence of this stimulant, all higher gangliosides inhibited the activity of GM2 synthase, the inhibition being more profound with increasing negative charge of the inhibiting gangliosides. These inhibitions are unspecific, but they do not exclude an end-product regulation of ganglioside biosynthesis. In detergent solubilized Golgi membranes, on the other hand, the inhibition pattern was completely different. Here, ganglioside GD1a was the strongest inhibitor of GM2 synthase, followed by GM1 and GM2, but GT1b also inhibited this enzyme appreciably, in fact more strongly than GM1 or GM2. On the other hand, GQ1b had no effect at all. Conversely, GD3-synthase activity was most strongly inhibited by GQ1b, followed by GT1b, but GD1a also inhibited this enzyme almost as strongly as GT1b. These latter findings indicate that feed-back control of the a- and the b-series pathways of ganglioside biosynthesis is probably not specific, but the pathways appear to be inhibited more preferably by their respective end-products than by any other gangliosides of the same of the other series. PMID- 3113446 TI - Primary structure and functional properties of the hemoglobin from the free tailed bat Tadarida brasiliensis (Chiroptera). Small effect of carbon dioxide on oxygen affinity. AB - The hemoglobin of the Free-Tailed Bat Tadarida brasiliensis (Microchiroptera) comprises two components (Hb I and Hb II) in nearly equal amounts. Both hemoglobins have identical beta-chains, whereas the alpha-chains differ in having glycine (Hb I) or aspartic acid (Hb II) in position 115 (GH3). The components could be isolated by DEAE-Sephacel chromatography and separated into the globin chains by chromatography on carboxymethyl-cellulose CM-52. The sequences have been determined by Edman degradation with the film technique or the gas phase method (the alpha I-chains with the latter method only), using the native chains and tryptic peptides, as well as the C-terminal prolyl-peptide obtained by acid hydrolysis of the Asp-Pro bond in the beta-chains. The comparison with human hemoglobin showed 18 substitutions in the alpha-chains and 24 in the beta-chains. In the alpha-chains one amino-acid exchange involves an alpha 1/beta 1-contact. In the beta-chains one heme contact, three alpha 1/beta 1- and one alpha 1/beta 2 contacts are substituted. A comparison with other chiropteran hemoglobin sequences shows similar distances to Micro- and Megachiroptera. The oxygenation characteristics of the composite hemolysate and the two components, measured in relation to pH, Cl-, and 2,3-bis-phosphoglycerate, are described. The effect of carbon dioxide on oxygen affinity is considerably smaller than that observed in human hemoglobin, which might be an adaptation to life under hypercapnic conditions. PMID- 3113448 TI - Adhesive properties of Pseudomonas aeruginosa isolated from urinary tract infections. AB - A research was carried out on the adhesive properties of 104 uropathogenic strains of P. aeruginosa. On the basis of the adhesiveness to various types of cell it was possible to identify the most frequent adhesive patterns. Moreover, the ability of some carbohydrates to inhibit the adhesiveness of P. aeruginosa and the effect of some enzymes on the agglutinability of human erythrocytes by non-hemagglutinating bacterial strains was studied. PMID- 3113447 TI - Animal models to study the cardiopulmonary effects of artificial kidney membranes. AB - Some adverse reactions occurring during hemodialysis have been suggested to be caused by the bioincompatibility of dialyzer membranes. Experimental sheep and swine models have been developed to study the biological effects of these membranes. Infusion of cuprophane-activated plasma into the animals produces drastic hematologic and cardiopulmonary alterations. Available data suggest that these alterations are mediated by complement activation products and arachidonic acid metabolites. The consistent and sensitive nature of these models makes them useful tools to further study the interactions between the blood elements and artificial kidney membrane surfaces. PMID- 3113449 TI - Acute confusional states (delirium) in the hospitalized elderly. PMID- 3113450 TI - Home care: process, outcome, cost. PMID- 3113451 TI - Respiratory physiology. PMID- 3113453 TI - Geriatric nursing in acute settings. AB - In conclusion, it is important to reiterate the interdependent nature of the functional health patterns as they relate to the geriatric patient in the acute care setting. Further, the combination of the primary nursing model with the functional health pattern approach that leads to subsequent nursing diagnoses provides a comprehensive care approach, which is so important for the elderly patient. As elders live longer, become frailer, and are subject to increasingly frequent hospitalizations, it will become more and more important to provide care in a manner that decreases fragmentation, increases individualization, and makes provisions for comprehensive and wholistic continuing care. PMID- 3113452 TI - Geriatric epidemiology. PMID- 3113454 TI - Elder neglect and abuse: a review of the literature. AB - The 31 pioneering studies tell us that elder neglect and abuse occur in various forms and are often inflicted on older women by relatives who are in a caregiving role. Yet, the studies' findings are insufficient to document the prevalence or to identify the cause(s) of elder mistreatment. Given our concern about elders and their families, further research is needed, guided by consideration of some priority issues (Callahan, 1982). The first question is what is and is not elder mistreatment and by whose definition. Since one's professional orientation has a major impact on one's perceptions, will we see what we expect or fear we will see when confronted with a possible mistreatment situation? Is elder mistreatment a legal problem, a criminal act, or is it one symptom of our society's lack of preparation for the care of its old-old? Research needs to address ways our society can prepare itself (families and communities) to care for our increasing population of old-old citizens. Second, as researchers, practitioners, and policymakers, we need to be clear about our own motives and incentives for focusing on elder mistreatment. Are our behaviors self-serving or other-serving? How can we each most effectively help our elders and their families and thus prevent the occurrence of elder mistreatment? Third, we need public and professional education that provides accurate information about aging, elder care, community resources, and elder mistreatment-education that can correct or counterbalance the mass media's misleading accounts. A fourth issue is the need to respond to the existence of elder mistreatment in reasonable ways so that social benefits will not exceed social costs. Greater effort and money put into programs that provide alternative forms of elder care and that support and assist families providing elder care will be most cost effective (human and monetary) in the long run than will laws that inappropriately decrease family privacy and control. We need to direct our energies and interventions at the causes, rather than the symptoms, of elder mistreatment. Finally, given the existing data base on elder mistreatment and the access barriers, consideration should be given to determining which research designs would produce the most valid, reliable, and useful findings. Gaining understanding of elder mistreatment-its antecedents, causes, and consequences-is prerequisite to effective and efficient prevention, identification, and treatment. PMID- 3113455 TI - Middle-ear pressure under basal conditions. AB - Spontaneous pressure changes in the middle ear were measured under basal conditions in ten subjects with healthy ears. A special "zero sweep rate" tympanometric procedure was developed in order to improve the accuracy of measurement. The respiratory carbon dioxide tension was recorded, and swallowings were indicated automatically. Results showed that the pressure in the majority of ears remained slightly above the atmospheric pressure. In some ears, the pressure increased during periods of drowsiness or sleep when the end-expiratory carbon dioxide tension was rising and the number of swallowings declined. In two ears, the middle-ear pressure showed a slow continuous increase during a two-hour observation period. The present results indicate that the gas turnover in the middle ear by diffusion shows a positive balance during basal conditions. Our findings thus speak against the common belief that the middle-ear gas is continuously being absorbed. PMID- 3113456 TI - The release of radioactive arachidonate from lipids of red blood cells during prolonged incubations in vitro. AB - Red blood cells were isolated from rat blood and incubated in the presence of [3H]arachidonate. A sizeable quantity (18%) of the radioactivity was incorporated into red cell lipids, of which phosphatidylcholine was the most highly labelled. Radioactive arachidonate was found at position 2 of this phospholipid. Free fatty acids were removed by washing the cells in solutions containing fatty-acid-free bovine serum albumin. The labelled red cells were then incubated for up to 16 h at 37 degrees C. After 16 h of incubation in saline-buffer-glucose or rat serum, 20 and 26%, respectively, of the total radioactivity was found in free fatty acids, and there were corresponding declines in the percentage radioactivities found in phosphatidylcholine. In the presence of serum, there was a more rapid release of radioactive fatty acid over the 2- to 16-h time course. There was not a significant drop in the phosphate levels of the total red cell phospholipids or phosphatidylcholine after 16 h of incubation and, as a result, there were large declines in the specific radioactivities of phosphatidylcholine. Diacylglycerols were not highly labelled and the action of phospholipase A2 on labelled phosphatidylcholine was indicated. When white blood cells were added to labelled red cells, there was little evidence of white cell involvement in the release of radioactive fatty acid, suggesting that the red cells themselves may be involved in arachidonate release. Red cells may serve as sources of arachidonate, released following hemorrhage in brain and metabolized to form various biologically active eicosanoids. PMID- 3113457 TI - An up-to-date method of early postoperative enteral feeding. AB - A case of early postoperative enteral feeding through a jejunostomically inserted catheter is reported. A child 9 years of age was operated upon for congenital brachyoesophagus. In the course of the operation a Jejunocath (Pfrimmer, Erlangen, FRG) was introduced to provide enteral nutrition with the oligopeptide diet Peptisorb (Pfrimmer). Punp controlled feeding was started on the first postoperative day. The amount of the diet was gradually raised in the first 4 postoperative days reaching a peak amount of 6980 kJoule/24 hours (230 kJ/kg BW). The maximum speed of administration was 80 ml/hour. No deviation in blood or urine was found, intestinal motility was normal. During ten days total and additional four days partial enteral feeding the child's bodyweight and skinfold thickness remained unchanged. It has been concluded that enteral feeding is a useful tool in postoperative nutrition in many cases. PMID- 3113458 TI - Indication of thioglucosidase activity in extracts of Neisseria gonorrhoeae. AB - The recent demonstration of a host-derived inducer of gonococcal resistance to complement-mediated killing by human serum in purified serum and red blood cell fractions, which contained small glucopeptides with cysteine as one of the constituent amino acids, prompted an investigation of Neisseria gonorrhoeae for thioglucosidase activity. This involved an examination of supernatants of sonicated gonococci for thioglucoside hydrolysis by following, spectroscopically, the hydrolysis of 6-purine beta-D-glucothiopyranoside to 6-mercaptopurine and glucose. Extracts of N. gonorrhoeae were found to hydrolyse this thioglucoside. A substantial activity was present in a fraction with the same order of molecular weight as plant thioglucosidases. This led us to suspect the presence of a thioglucosidase in N. gonorrhoeae. PMID- 3113460 TI - Cloning of two possible haemolysin determinants from Listeria monocytogenes. PMID- 3113461 TI - Response of AIDS-related thrombocytopenia to intravenous and oral azidothymidine (3'-azido-3'-deoxythymidine). AB - A patient with AIDS-related thrombocytopenia (ART) was treated with the new anti retroviral agent azidothymidine (AZT, Retrovir, zidovudine) by the intravenous and oral routes for a period of 20 weeks. After a 6 week period of initial treatment, the platelet count rose from 38,000 to 140,000/mm3. AZT was intentionally discontinued for three weeks over which the platelet count declined to 70,000/mm3. After reinstitution of AZT, the platelet count rose once again and remained near normal levels for over one year. We conclude that AZT may have efficacy against the thrombocytopenia observed in some patients infected with human immunodeficiency virus (HIV). The pathogenesis of ART and the mechanisms of action of AZT in this condition remain unknown. PMID- 3113462 TI - Therapy of acquired immune deficiency syndrome with recombinant interleukin-2. AB - Recombinant human interleukin-2 (rIL-2) was administered to 87 patients with the acquired immune deficiency syndrome (AIDS) to test the hypothesis that this lymphokine would correct the underlying qualitative and quantitative deficiency in cellular immunity. Patients were divided into two groups by the presence or absence of Kaposi's sarcoma and subjects within each of these groups received intravenous rIL-2 three times weekly for eight weeks. Subjects received one of several doses which ranged from 1,000 to 2,000,000 units per square meter body surface area. Toxicity at high doses consisted of flu-like symptoms and hypotension at highest doses. Partial objective tumor regression was observed in three patients with Kaposi's sarcoma. Seventeen patients had progression of disease (new opportunistic infection or increase in Kaposi's sarcoma) during therapy. No improvement in immunologic status was observed. This study does not suggest a role for single-agent rIL-2 therapy of established AIDS but its use in less symptomatic persons or in conjunction with antiretroviral agents such as azidothymidine should be investigated. PMID- 3113459 TI - The 70-Kd neisserial common antigen is a surface-exposed, antigenically stable peptidic structure. AB - A previously described 70-Kd antigen present in all Neisseria gonorrhoeae strains tested and in most Neisseria species was characterized as a mercaptoethanol-and heat-stable protein. Using mouse polyclonal antisera specifically directed against this antigen, it was shown that it is a surface-exposed structure. The 70 Kd antigen was recovered from all gonococcal strains isolated from different anatomic sites in male and female partners, thus demonstrating its antigenic stability after in vivo transmission in humans. PMID- 3113463 TI - Activity of interferons alpha, beta, and gamma against human immunodeficiency virus replication in vitro. AB - The antiviral activities of various interferon preparations against human immunodeficiency virus (HIV) were evaluated in vitro. Recombinant interferon alpha-A, and beta interferons and leukocyte-derived alpha interferons show similar concentration-dependent antiviral activity. Recombinant and lymphocyte derived gamma interferons show minimal antiviral activity against HIV replication in normal peripheral blood mononuclear cells, but definite activity against HIV in the H9 lymphocytic and U937 monocyte-macrophage cell lines. PMID- 3113464 TI - Quantitative immunocytofluorographic analysis of CD4 surface antigen expression and HIV infection of human peripheral blood monocyte/macrophages. AB - HIV infection of CD4-bearing lymphocytes alone does not fully explain the immune dysfunction of AIDS. Monocyte/macrophages infected with HIV may serve as a reservoir of HIV, may function abnormally and may transmit infection to other susceptible cells, thus playing a central role in the development of the immunodeficiency of AIDS. Quantitative analysis of surface antigens and measurement of HIV antigens in infected cells have been difficult using the conventional approach of immunofluorescent staining of cells on slides. We have developed a system that maintains monocyte/macrophages in suspension culture for at least four months. Through immunocytofluorographic single cell analysis we have shown that CD4 antigen is present on monocytes, and that a tenfold increase in expression occurs during the first two weeks in culture. In contrast, LeuM3 antigens decreased to background levels in the course of long-term culture. Using anti-HIV p24 antibody, we have demonstrated that monocyte/macrophages can be infected with HIV. Up to 70% of cells from individual donors could be infected. The techniques herein described allow in vitro quantitation of some of the mechanisms by which HIV infection of monocyte/macrophages may contribute to the immunodeficiency states associated with AIDS. PMID- 3113465 TI - [Cerebral blood flow measurement using H2(15)O intravenous injection and positron emission tomography: description of implementation and applications to cerebrovascular reactivity measurement]. AB - The method for cerebral blood flow (CBF) measurement using an H215O intravenous injection and positron emission tomography (PET) was implemented, examined and applied to measure cerebrovascular reactivity to PaCO2(VRCO2) and to MABP (VRBP) in normal brain and in ischemic brain. Immediately after bolus intravenous injection of 30-40 mCi H2(15)O, a time-activity curve of H2(15)O concentration in the arterial blood and in the brain were measured for 60 sec by a beta detector and a PET, respectively. The PET was HEADTOME III and measured five planes. CBF was determined by the table-look up method based on the autoradiographic principle. Six volunteers were studied to examine region of VRCO2, and a moyamoya patient and a stroke patient with a bilateral-intracarotid circulation defect were studied to examine VRCO2 and VRBP in ischemic brain. The studies were carried out so as to be followed two or three H2(15)O CBF measurements with changing PaCO2 or MABP after control study at rest condition. In addition, prior to the H2(15)O study O15 gas steady state study was performed on all subjects. Validity of the method examined by simulation studies showed 3% error per 1 sec time shift of the artery curve for 60 sec PET scan duration and the error was rapidly increased to the shorter scan duration. Inhomogeneity of a brain tissue gave mild under-estimation by 5% for 60 sec PET scan duration. VRCO2 in normal brain was revealed to be almost uniform except that the infratentorium area showed a slight higher VRCO2 than the supratentorium area. The ischemic brain showed a negative correlation between VRCO2 and oxygen extraction fraction (OEF), and a positive correlation between VRBP and OEF. PMID- 3113466 TI - Possible face-mask hazard. PMID- 3113467 TI - Low-dose phenobarbitone as an indicator of compliance with drug therapy. AB - 1 To assess the potential value of low-dose phenobarbitone (PB) as a marker of compliance we studied the relationship between plasma level of PB and dose (2-16 mg daily) following 3 or 4 weeks treatment in healthy volunteers (n = 26) and in patient volunteers (n = 7). 2 Also, to simulate poor compliance, PB levels were measured in some volunteers following alternate-day (n = 6) or short-term (n = 5) treatment with similar doses. These levels, expressed as the level: dose ratios (LDRs), did not overlap with those obtained following 3 or 4 weeks of daily PB intake. 3 To evaluate the efficacy of this marker in patients taking other drugs we gave a group of out-patients (n = 24) compound tablets containing B vitamins and a small dose (16 mg) of PB; their compliance over 2-5 weeks was assessed both by measuring plasma levels of PB and residual tablet counting. 4 In the latter study, as well as providing absolute evidence of good compliance by many patients, the plasma levels of PB proved particularly valuable when non-compliant individuals 'forgot' to bring their residual tablets. 5 We suggest that phenobarbitone, in doses low enough to be non-sedative and non-enzyme inducing, is potentially useful as a pharmacological indicator of compliance with drug therapy. PMID- 3113469 TI - Flecainide plasma concentrations correlated to inhibition of a bundle of Kent. PMID- 3113468 TI - Effect of arachidonic acid on anthralin inflammation. AB - 1 The effect of topical arachidonic acid on anthralin inflammation was studied using sequential measurements of erythema (reflectance photometry) and oedema (calipers). 2 Topical arachidonic acid in concentrations which produced a small short-lived inflammatory response greatly augmented the initial phase and depressed the later phase of the inflammatory response to anthralin. 3 The initial augmentation was inhibited by concomitant administration of alpha tocopherol. 4 It is suggested that free radical formation by anthralin has a direct action on membrane substrates such as arachidonic acid forming inflammatory products by a non-enzymic process. PMID- 3113470 TI - Determination of cell-free interleukin 2 receptor level in the serum of normal animals and of animals bearing IL-2 receptor positive tumours with high or low metastatic capacity. AB - Serum levels of cell-free interleukin-2 receptors were elevated above normal in mice bearing the IL-2R positive T-cell lymphoma Eb or its highly metastatic variant ESb. Although ESb cells expressed less IL-2R molecules than Eb cells on their cell surface, serum receptor levels were raised more quickly in ESb than in Eb tumour bearing animals. Elevated IL-2R serum levels were a sensitive tumour marker in animals bearing the aggressive variant ESb but not in animals bearing the low metastatic line Eb. Peritoneal ascites tumour-bearing animals had higher serum IL-2R levels than corresponding animals with subcutaneously growing tumours. Thus, serum IL-2R levels in tumour-bearing animals were dependent on the tumour line and influenced by the site and mode of tumour growth. PMID- 3113471 TI - Loss of epithelial cell surface carbohydrates during experimental oral carcinogenesis in the rat. AB - Cell surface glycoconjugates were investigated in a rat model of oral chemical carcinogenesis. The lectins Griffonia simplicifolia (GS-I-B4; specific for alpha D-galactosyl end groups) and Ulex europeus (UEA-I; specific for alpha-L-fucosyl groups) were examined microspectrofluorimetrically in the oral epithelium of rats painted with the carcinogen 4-nitroquinoline N-oxide (4NQO) and compared with those treated with solvent alone. After labelling with GS-I-B4, the fluorescent intensity of the basal and parabasal epithelial cells was significantly less after 9 months of 4NQO treatment and in overt squamous cell carcinomas compared to controls. The fluorescent activity of the spinous epithelial cells in the non invasive tissues treated with 4NQO and in the well differentiated (sites of keratin elaboration) malignant epithelium of squamous cell carcinomas was unchanged after labelling with UEA-I. UEA-I failed to stain undifferentiated (areas lacking keratin) malignant epithelium. The findings indicate that alpha-D galactosyl residues are diminished on the membranes of premalignant and malignant rat epithelial cells. The expression of alpha-L-fucosyl groups, however, remains unchanged in premalignant rat oral epithelium and is closely correlated to the presence of keratin in the malignant epithelium of squamous cell carcinomas. PMID- 3113472 TI - Cholestyramine promotes 7,12-dimethylbenzanthracene induced mammary cancer in Wistar rats. AB - The promotion of 7,12-dimethylbenzanthracene (DMBA) induced mammary cancer in Wistar rats by a 4% cholestyramine (CHST) diet was investigated. The rats, 50 days of age, were divided into six groups. First two groups were given an intragastric dose of 0.8 ml of corn oil whereas the remaining four groups were given a single intragastric dose of 5 mg of DMBA dissolved in 0.8 ml of corn oil. After 1 week on laboratory chow the first two groups and two groups treated with DMBA were fed a control diet and the two remaining groups treated with DMBA were fed a 4% CHST diet. Half the animals were killed at 100 days and the remainder at 200 days. A detailed histologic examination of grossly normal mammary tissue as well as any tumour mass was made for each rat. The serum lipids were extracted and the individual neutral lipid composition was determined. In rats treated with DMBA and fed a 4% CHST diet, the incidence of malignant tumours increased by 5 fold, and the tumour weight by 12 fold. In addition, the serum total lipids, cholesterol esters and triglycerides decreased significantly when compared with rats fed a control diet. These results suggest that CHST diet promotes DMBA induced mammary cancers in Wistar rats. PMID- 3113473 TI - Monoclonal antibodies to factor VIII: their application in immunoblotting for the visualization of factor VIII in therapeutic concentrates and plasma. AB - Two monoclonal antibodies (McAb) termed 12A4 and 19C1 have been raised against human factor VIII. In immunoassays 12A4 bound to factor VIII antigen (VIII:Ag) in plasma but not serum whilst 19C1 bound to VIII:Ag in both plasma and serum. Both McAb were shown by immunoblotting to react with the carboxy (C) terminal polypeptide of factor VIII which appeared as a doublet with a molecular weight (Mr) of 77,000/75,000. The C terminal factor VIII polypeptide was detectable by immunoblotting in each of 12 therapeutic factor VIII concentrates, from six different manufacturers, although its level was variable. Factor VIII was visualized in plasma by immunoblotting following its immunoadsorption and elution from agarose-bound monoclonal antibodies. No Mr 77,000/75,000 bands were detectable in plasma obtained from 13 unrelated CRM- haemophiliacs whilst 11 CRM+ haemophilic plasmas from seven kindred were shown to have a C terminal factor VIII polypeptide of normal molecular size. PMID- 3113474 TI - A different example of autoimmune haemolytic anaemia caused by anti-D. PMID- 3113476 TI - Endocrine changes following pituitary desensitization with LHRH agonist and administration of purified FSH to induce follicular maturation. AB - Pituitary desensitization was induced in 13 normally menstruating women by administration of an LHRH agonist, Buserelin, intranasally, 100 micrograms at intervals of 4 h, for a period of 14 days starting on day 22 of the menstrual cycle. Whilst continuing with Buserelin, multiple follicular development was induced by administration of purified FSH (Metrodin) for between 8 and 15 days at a dose of 150 i.u. daily. In one patient no follicular growth was induced after 14 days treatment. In the remaining subjects between 3 and 11 follicles with mean diameter greater than 16 mm were stimulated and between 2 and 10 mature oocytes were recovered laparoscopically for IVF, 34 h after hCG administration. Eight patients underwent embryo transfer and four conceived. PMID- 3113475 TI - Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women. AB - The use of oestrogens in the treatment of genuine stress incontinence was assessed by a double-blind prospective trial in 36 postmenopausal women with genuine stress incontinence who received 3 months of cyclical treatment with either piperazine oestrone sulphate or a matching placebo. Patients were assessed subjectively and objectively before and after treatment by 7-day bladder charts, urethral pressure profiles (UPP), the Urilos nappy test, vaginal cytology and hormone assays (plasma oestrogens and gonadotrophins). There was no statistical difference in the subjective response to treatment between the two groups. After 6 weeks of treatment there was a greater reduction in the number of pad changes/24 h in the oestrogen-treated patients that approached statistical significance but, because of a marked response in the placebo group, this difference was not significant after 3 months of treatment. There were also no significant differences between the two groups with respect to the UPP or Urilos measurements but the vaginal cytology and hormone profiles were significantly affected by oestrogens. In view of the possible risks of oestrogen therapy its use in genuine stress incontinence is limited. PMID- 3113477 TI - Acceleration of surface-dependent autocatalytic activation of blood coagulation factor XII by divalent metal ions. AB - The effect of divalent metal ions on the rate of dextran sulfate dependent autocatalytic activation of human blood coagulation factor XII was studied at pH 7.4 and 25 degrees C. Zn2+ and Cu2+, but not Co2+, increased the rate of factor XII activation induced by dextran sulfate with optimum effects at approximately 5 and 1 microM, respectively, while Ca2+ acceleration required much higher concentrations (millimolar). Further investigation of the effect of Zn2+ on factor XII activation demonstrated a complete dependence on the presence of dextran sulfate, lack of inhibition by soybean trypsin inhibitor, the appearance of alpha-XIIa as the primary reaction product, and reaction kinetics characteristic of an autocatalytic process. These results were consistent with Zn2+ affecting only the rate of surface-mediated factor XII autoactivation. The initial turnover velocity of dextran sulfate induced factor XII autoactivation increased linearly with factor XII concentration in the absence of Zn2+ up to 0.9 microM factor XII but showed saturation behavior over this same concentration range in the presence of 5 microM Zn2+, indicating that Zn2+ increased the reaction rate primarily by lowering the apparent Km. Comparison of the kinetics of autoactivation at mu = 0.15 and 0.24 revealed that the enhancement in the apparent kcat/Km brought about by Zn2+ increased from 19-fold to 520-fold, respectively, due to a differential dependence of the Zn2+-stimulated and unstimulated reactions on ionic strength.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113478 TI - Regulation of cytochrome P-450j, a high-affinity N-nitrosodimethylamine demethylase, in rat hepatic microsomes. AB - Polyclonal antibodies were produced in rabbits against purified cytochrome P-450j isolated from isoniazid-treated adult male rats. The monospecificity of immunoadsorbed antibody to cytochrome P-450j was demonstrated by Ouchterlony double diffusion analyses, enzyme-linked immunosorbent assays, and immunoblots. Immunoquantitation results indicated that rat liver microsomal cytochrome P-450j content decreases between 3 and 6 weeks of age in both the male and female animal. Several xenobiotics, such as Aroclor 1254, mirex, and 3 methylcholanthrene, repressed cytochrome P-450j levels when administered to male rats. Isoniazid, dimethyl sulfoxide, pyrazole, 4-methylpyrazole, and ethanol were inducers of cytochrome P-450j in rat liver although these compounds showed different inducing potencies. Microsomes from adult male rats with chemically induced diabetes also contained elevated levels of cytochrome P-450j compared to untreated animals. Cytochrome P-450j levels were measurable in kidney, whereas this isozyme was barely detectable in lung, ovaries, and testes; however, extrahepatic cytochrome P-450j was inducible by isoniazid. Approximately 80-90% of microsomal N-nitrosodimethylamine demethylation was inhibited by antibody to cytochrome P-450j whether the microsomes were isolated from untreated rats or animals administered inducers or repressors of cytochrome P-450j. The residual catalytic activity resistant to antibody inhibition may be a reflection of the inaccessibility of a certain amount of cytochrome P-450j due to interference by NADPH-cytochrome P-450 reductase based on results obtained with the reconstituted system. There was a good correlation (r2 = 0.87) between cytochrome P-450j content and N-nitrosodimethylamine demethylase activity in microsomes from rats of different ages and treated with various xenobiotics. The evidence presented indicates that cytochrome P-450j is the primary, and perhaps sole, microsomal catalyst of N-nitrosodimethylamine demethylation at substrate concentrations relevant to hepatocarcinogenesis induced by N-nitrosodimethylamine. PMID- 3113480 TI - Binding protein-dependent transports in 2-oxo acids dehydrogenase mutants of Escherichia coli. AB - The binding protein-dependent transport of ribose, galactose and maltose are reduced in several 2-oxo acids dehydrogenase mutants of Escherichia coli. The results suggest an implication of the pyruvate dehydrogenase complex and to a lesser extent of the 2-oxoglutarate dehydrogenase complex in the energization of these transport systems. PMID- 3113479 TI - Zwitterionic detergent mediated interaction of purified cytochrome P-450LM4 from 5,6-benzoflavone-treated rabbits with MADPH-cytochrome P-450 reductase. AB - Hydroxylation of acetanilide catalyzed by purified cytochrome P-450LM4 and NADPH cytochrome P-450 reductase was reconstituted with the zwitterionic detergent 3 [(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). The optimum rate of production of 4-hydroxyacetanilide was observed between 3 and 7 mM CHAPS and was about half that with 0.05 mM dilauroylglyceryl-3-phosphocholine (di-12-GPC). At higher detergent concentrations, hydroxylase activity decreased until at 15-20 mM CHAPS the system was inactive. The effect of CHAPS on the state of aggregation of P-450LM4 and on interaction between the cytochrome and P-450 reductase alone and under turnover conditions was investigated by ultracentrifugation. At 4 mM CHAPS, P-450LM4 was hexameric to heptameric (Mr 369,000). Neither reductase nor reductase plus acetanilide and NADPH altered the state of P-450LM4 aggregation, suggesting that a stable 1:1 P-450/reductase complex did not form under turnover conditions. Replacing CHAPS with 0.05 mM di-12-GPC resulted in formation of heterogeneous P-450 oligomers (Mr greater than 480,000). At CHAPS concentrations where substrate hydroxylation did not occur (15 and 22 mM), P-450LM4 was shown by sedimentation equilibrium measurements to be dimeric and monomeric, respectively. P-450 reductase was shown to reduce monomeric P-450LM4 in the presence of NADPH. Thus, the dependence of hydroxylase activity on [CHAPS] may be related to the state of aggregation of the cytochrome. An apparent correlation between P-450 aggregation state and NADPH-supported hydroxylation was also observed with phenobarbital-inducible P-450LM2 in the presence of detergents [Dean, W.L., & Gray, R.D. (1982) J. Biol. Chem. 257, 14679-14685; Wagner, S.L., Dean, W.L., & Gray, R.D. (1984) J. Biol. Chem. 259, 2390-2395]. PMID- 3113481 TI - Effects of divalent cations on the ultrasonic absorption coefficient of negatively charged liposomes (LUV) near their phase transition temperature. AB - The ultrasonic absorption coefficient per wavelength (alpha lambda), as a function of temperature and frequency, was determined for large unilamellar vesicles (LUV) in the vicinity of their phospholipid phase transition temperature, using a double crystal acoustic interferometer. (The vesicles were composed of a 4:1 (w/w) mixture of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG). It has been found that alpha lambda reaches a maximum (alpha lambda)max at the phase transition temperature (tm) of the phospholipids in the bilayer, at an ultrasonic relaxation frequency of 2.1 MHz. Divalent cations (Ca2+ and Mg2+), added to LUV suspensions, shifted (alpha lambda)max to higher temperatures, dependent upon the concentration of divalent cation. It was also found that the shape of the alpha lambda versus t curve was significantly changed, representing changes in the Van't Hoff enthalpy of the transition, and therefore, the cooperative unit of the transition. This suggests that divalent cations interact individually with the negatively charged phospholipid headgroups of DPPG and with DPPC headgroups, thus decreasing the cooperative unit of the transition. The observed upward shift in tm suggests an interaction that increases the activation energy and, therefore, the temperature of the phase transition. However, alpha lambda as a function of frequency did not change with the addition of divalent cations and, thus, the relaxation time of the event responsible for the absorption of ultrasound is not changed by the addition of divalent cations. PMID- 3113482 TI - Preparation of fluorescent derivatives of lipases and their use in fluorescence energy transfer studies in hydrocarbon/water interfaces. AB - Fluorescein isothiocyanate reacted with a chromobacter and pseudomonad lipase to yield mono-substituted, fully active, enzymes. With the carbocyanine dye 1,1' dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) in the non aqueous phase, fluorescence energy transfer was used to follow the lipase and similarly labelled model proteins in and out of the interface in heptane, and heptane/di-O-palmitoyl-rac-glycerol (a substrate analogue), emulsions. Competitive binding, and displacement by other proteins could also be followed. PMID- 3113483 TI - Characterization of guinea-pig high-molecular-weight kininogen as multi functional molecule. AB - High-molecular-weight (HMW) kininogen was purified from guinea-pig plasma by measuring its ability to correct the prolonged clotting time in human HMW kininogen deficient plasma (Fitzgerald trait). The purified HMW kininogen demonstrated a homogeneous band in disc gel electrophoresis in the presence of sodium dodecyl sulfate under reducing or non-reducing conditions with an apparent molecular weight of 100,000. Kinin released from HMW kininogen by treatment with guinea-pig plasma kallikrein was identified as bradykinin by reverse-phase HPLC and amino-acid analysis. The capacity of HMW kininogen as a thiol-proteinase inhibitor was realized by its dose-dependent inhibitory activity to papain. The Ki value for papain was estimated to be 42 pM. The kinin-free HMW kininogen maintained the inhibitor and clotting-factor activities with similar capacities to those of the HMW kininogen molecule. Heavy chain (H-chain) and light chain (L chain) of HMW kininogen were prepared from reduced and alkylated kinin-free HMW kininogen by HPLC. The S-alkylated H-chain, but not L-chain, demonstrated the inhibitor activity with the Ki value 6.9 nM for papain, whereas the S-alkylated L chain, but not H-chain, maintained the clotting activity one-third of the capacity of HMW kininogen. Specific antibodies recognized HMW kininogen, but also a probable low-molecular-weight kininogen(s) with an apparent molecular weight of 60,000 in the guinea-pig plasma. All of these properties are consistent with the reports on human, bovine and rat HMW kininogen. PMID- 3113485 TI - Kinetic characterization of rabbit skeletal muscle phosphorylase ab hybrid. AB - Phosphorylase ab was prepared in vitro by partial phosphorylation of rabbit skeletal muscle phosphorylase b and was isolated by DEAE-Sephacel chromatography. Its phosphorylated and non-phosphorylated subunits could not be distinguished by different affinity to substrates, activators or inhibitors, indicating their coordinated function. In the absence of nucleotide activators, the Km values for Pi and glucose-1-P were 28 mM and 18 mM, respectively. Activity in the presence of 16 mM glucose-1-P was doubled by 10(-4) M AMP or 10(-3) M IMP, mainly by lowering the Km for glucose-1-P. Half-maximum activation was exerted by 2 microM AMP or 0.1 mM IMP. Activation by these nucleotides showed no cooperativity. Glucose exerted competitive inhibition with respect to glucose-1-P, while for the inhibition by glucose-6-P an allosteric mechanism is suggested; the appropriate Ki values were 4.5 mM and 1.5 mM, respectively. The Hill coefficient for glucose 1-P binding was about 1.0, even in the presence of glucose (up to 10 mM), but 10 mM glucose-6-P lowered it to 0.47, indicating a negative heterotropic cooperativity. Effective regulation of the activity of phosphorylase ab by physiological concentrations of Pi, AMP, IMP and glucose-6-P suggests its metabolic control under in vivo condition. PMID- 3113484 TI - A strong carboxylate-arginine interaction is important in substrate orientation and recognition in lactate dehydrogenase. AB - Using site-directed mutagenesis, Arginine-171 at the substrate-binding site of Bacillus stearothermophilus, lactate dehydrogenase has been replaced by lysine. In the closely homologous eukaryotic lactate dehydrogenase, this residue binds the carboxylate group of the substrate by forming a planar bifurcated bond. The mutation diminishes the binding energy of pyruvate, alpha-ketobutyrate and alpha ketovalerate (measured by kcat/Km) by the same amount (about 6 kcal/mol). For each additional methylene group on the substrate, there is a loss of about 1.5 kcal/mol of binding energy in both mutant and wild-type enzymes. From these parallel trends in the two forms of enzyme, we infer that the mode of productive substrate binding is identical in each, the only difference being the loss of a strong carboxylate-guanidinium interaction in the mutant. In contrast to this simple pattern in kcat/Km, the Km alone increases with substrate-size in the wild type enzyme, but decreases in the mutant. These results can be most simply explained by the occurrence of relatively tight unproductive enzyme-substrate complexes in the mutant enzyme as the substrate alkyl chain is extended. This does not occur in the wild-type enzyme, because the strong orienting effect of Arg-171 maximizes the frequency of substrates binding in the correct alignment. PMID- 3113486 TI - Influence of N,N-dimethylaniline on the association of phenobarbital-induced cytochrome P-450 and NADPH-cytochrome c(P-450) reductase in a reconstituted rabbit liver microsomal enzyme system. AB - N,N-Dimethylaniline when added to reaction mixtures provokes deviation from Michaelis-Menten law of the interaction kinetics of NADPH-cytochrome c(P-450) reductase (NADPH:ferrihaemoprotein oxidoreductase, EC 1.6.2.4) with highly purified phenobarbital-induced rabbit liver microsomal cytochrome P-450 (P 450LM2). This phenomenon is not associated with the low-to-high spin transition in the iron-coordination sphere of the haemoprotein, as elicited by the arylamine. Substrate-triggered departure from linearity of the kinetics is abolished by inclusion into the assay media of p-chloromercuribenzoate, hinting at a vital role in the process of thiols. Similarly, the parabolic progress curve (nH = 1.7) is transformed to a straight line (nH = 1.01) when the N-terminal reductase-binding domain in the P-450LM2 molecule is selectively blocked through covalent attachment of fluorescein isothiocyanate (FITC); such a modification does not alter the affinity of the haemoprotein for the amine substrate. Steady state fluorescence polarization measurements reveal that N,N-dimethylaniline perturbs the motional properties of the fluorophore-bearing reductase-binding region, suggesting the induction of a conformational change. Summarizing these results, the data possibly indicate N,N-dimethylaniline-induced cooperativity in the association of reductase with P-450LM2. PMID- 3113487 TI - Conversion of linoleic acid and arachidonic acid by skin epidermal lipoxygenases. AB - Two different lipoxygenases have been identified in human and rat epidermis. One lipoxygenase has a (n-9)-specificity, converts arachidonic acid into 12 hydroxyeicosatetraenoic acid (12-HETE), and has been described by several investigators. Linoleic acid is not a substrate for this enzyme. The other lipoxygenase, with (n-6)-specificity, converts arachidonic acid into 15-HETE and linoleic acid into 13-hydroxyoctadecadienoic acid (13-HOD). Especially the latter lipoxygenase is thought to be involved in the regulation of the differentiation of the skin cells into a proper water-barrier layer. Linoleate is supposed to be the physiological substrate; this fatty acid is especially present in characteristic sphingolipids with unique structures. PMID- 3113489 TI - Human neutrophil platelet-activating factor: molecular heterogeneity in unstimulated and ionophore-stimulated cells. AB - The molecular heterogeneity of platelet-activating factor (PAF) in resting and ionophore (A23187) -stimulated human neutrophils was measured by a very sensitive gas chromatography-negative ion chemical ionization mass spectrometric method. The molecular species compositions of PAF, which are due to variations in the 1-O alkyl chain length, were significantly different between resting and ionophore stimulated polymorphonuclear leukocytes. The major species of PAF produced by unstimulated polymorphonuclear leukocytes were 16:0, 17:0, 18:1 and 18:0, representing 55, 14, 8 and 10%, respectively, of the total PAF; 16:0 was the predominant PAF (74%) in A23187-stimulated polymorphonuclear leukocytes. The PAF molecular species from unstimulated polymorphonuclear leukocytes was similar to compositions from those of the precursor 1-O-alkyl-2-acyl-sn-glycero-3 phosphocholine, whereas those from the ionophore-stimulated polymorphonuclear leukocytes differed from the precursor 1-O-alkyl-2-acyl-sn-glycero-3 phosphocholine, thus indicating a very high degree of substrate selectivity for PAF synthesis. Although the physiological implications of the variations in PAF composition are not known, these studies indicate that the PAF produced by resting polymorphonuclear leukocytes are significantly different from those produced in response to ionophore. PMID- 3113488 TI - Short-term diabetes increases triacylglycerol arachidonic acid content in the rat liver. AB - Fatty acid compositions of liver phospholipid, cholesterol ester and triacylglycerol fractions obtained from streptozotocin-induced diabetic rats were compared to those from control or from simple-acidotic rats. Significant reductions of arachidonic acid proportions in phospholipid and cholesterol ester were found on the 3rd day after the streptozotocin treatment. In triacylglycerol, arachidonic acid and the other desaturation and elongation products of linoleic acid except for gamma-linolenic acid were increased in the diabetic rats. Although essential fatty acid composition in liver phospholipid and cholesterol ester of simple-acidotic rats did not differ from control rats, dihomo-gamma linolenic acid, arachidonic acid, adrenic acid and docosapentaenoic acid (22:5(n 6] contents in liver TG were significantly increased over those in control rats and were similar to those in diabetic rats. These results suggest that metabolic acidosis may contribute to the fatty acid abnormalities observed in diabetic animals. PMID- 3113490 TI - Ethanol induces release of arachidonic acid but not synthesis of eicosanoids in mouse peritoneal macrophages. AB - Exposure of mouse peritoneal macrophages to ethanol induces a rapid release of arachidonic acid to the extracellular medium. All major classes of phospholipids, phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol contribute to this release. Ethanol-induced mobilization of arachidonic acid occurs by deacylation, but it is not accompanied by eicosanoid synthesis. These data suggest that at least two signals are necessary for the release and metabolism of arachidonic acid. Ethanol also activates a phospholipase C which hydrolyzes only phosphatidylinositol, and not its phosphorylated derivatives. PMID- 3113491 TI - The effect of temperature and ionic strength on the apparent Ca-affinity of EGTA and the analogous Ca-chelators BAPTA and dibromo-BAPTA. AB - The apparent calcium association constants (K'Ca) of ethylene glycol bis(beta aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), 1,2-bis(o aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and 1,2-bis 2-bis(o-amino 5-bromophenoxy)ethane-N,N,N',N'-tetraacetic acid (dibromo-BAPTA) were measured using the method described by Bers (Am. J. Physiol. 242 (1982) C404-408). The purity of the three ligands determined from the chi-intercept of Scatchard plots were 96.3%, 79.0% and 97.3% for EGTA, BAPTA and dibromo-BAPTA, respectively. The impurity of BAPTA was found to be water by drying several samples to constant weight. Increasing temperature from 1 to 36 degrees C led to an increase in K'Ca which was of similar magnitude for the three ligands. Increasing ionic strength from 0.104 to 0.304 M led to a reduction of K'Ca in all cases, though EGTA was affected much less than BAPTA or dibromo-BAPTA. Experimental results were compared with values of K'Ca calculated from the individual association constants of the ligands for calcium and protons which were modified for the experimental conditions using the Debye-Huckel limiting law and the Van't Hoff Isochore to correct for ionic strength and temperature, respectively. The experimental values of K'Ca of EGTA agree well with those in the literature and with the calculated values. Good agreement was also found between the experimental and calculated values of K'Ca for the temperature and ionic strength dependence of BAPTA and dibromo-BAPTA. PMID- 3113493 TI - Effect of metal ions on the rearrangement of dopachrome. AB - In vitro experiments are reported showing that a number of transition metal ions exert a profound influence on both the kinetics and chemical course of the rearrangement of dopachrome, a key step in the biosynthesis of melanins. HPLC analysis shows that Cu2+, Ni2+ and Co2+ are particularly effective in inducing the non-decarboxylative rearrangement of dopachrome at physiological pH values, leading mainly to 5,6-dihydroxyindole-2-carboxylic acid, whereas in the absence of metal ions the reaction proceeds with concomitant loss of carbon dioxide to give almost exclusively 5,6-dihydroxyindole. Kinetic experiments provide evidence that the rate of the metal-promoted rearrangement is first order with respect to both aminochrome and metal concentration and decreases in the presence of increasing concentrations of EDTA, consistent with a mechanism involving a direct 1:1 dopachrome-metal ion interaction in the transition state. When considered in the light of the known metal accumulation in pigmented tissues, the results of this study provide a new entry into the regulatory mechanisms involved in the biosynthesis of melanins. PMID- 3113492 TI - Analysis of tumor-promoter-induced inflammation in rats: participation of histamine and prostaglandin E2. AB - Inflammatory reactions induced by TPA (12-O-tetradecanoylphorbol 13-acetate)-type tumor promoters, including TPA, teleocidin and aplysiatoxin, and chemical mediators responsible for such inflammatory reactions were analyzed. The tumor promoter dissolved in a 0.8% sodium carboxymethyl cellulose solution was injected into a subcutaneous air pouch preformed on the dorsum of rats. Within 30 min after the injection, vascular permeability as measured by the leakage of labeled albumin into the pouch fluid was increased, with a concomitant increase in histamine level. This increase in vascular permeability was inhibited by a histamine antagonist, pyrilamine, and a serotonin antagonist, methysergide. Vascular permeability at 4 h was not inhibited by pyrilamine or methysergide but was inhibited by a cyclooxygenase inhibitor, indomethacin, with a parallel decrease in the prostaglandin E2 level in the pouch fluid. These results suggest that the TPA-type tumor promoters induce inflammation by the mechanism of mast cell degranulation within a short period, this being followed by the stimulation of arachidonic acid metabolism. The mechanism of the in vivo effect of the TPA type tumor promoters is discussed and compared with in vitro effects that we have previously reported. PMID- 3113494 TI - Identity of beta-alanine-oxo-glutarate aminotransferase and L-beta aminoisobutyrate aminotransferase in rat liver. AB - L-beta-Aminoisobutyrate served as an amino donor for purified beta-alanine-oxo glutarate aminotransferase from rat liver when 2-oxoglutarate was employed as an amino acceptor, but the D-isomer did not. L-beta-Aminoisobutyrate acted as a competitive inhibitor with respect to beta-alanine and had a Ki of approximately 2.6 mM, which is the same value as the Km of 2.7 mM. When the crude extract was applied to a DEAE-Sepharose CL-6B column, L-beta-aminoisobutyrate aminotransferase and beta-alanine-oxo-glutarate aminotransferase activities were found in the same fractions with a single peak. Antiserum to rat liver beta alanine-oxo-glutarate aminotransferase inhibited L-beta-aminoisobutyrate aminotransferase activity in rat liver in the same way as beta-alanine-oxo glutarate aminotransferase activity. PMID- 3113495 TI - Alterations in the intermediary metabolism of selenium-deficient mice. AB - Male albino mice were pair-fed a torula yeast-based selenium-deficient (Se-) diet containing 10 ppb selenium for 4 months, while a control group (Se+) received a similar diet supplemented with 330 ppb selenium as Na2SeO3. In addition to previously observed modulations of drug-metabolizing enzymes (Reiter, R. and Wendel, A. (1985) Biochem. Pharmacol. 34, 2287-2290), an increase of 6 phosphogluconate dehydrogenase activity and succinate dehydrogenase activity in liver by about 60% was found. In vivo, an increased 14CO2 exhalation from a tracer dose of glucose either labeled in the C-1- or C-6 position was observed in selenium-deficient mice. However, no difference in the total CO2 exhalation of Se(-)- as compared to Se+-mice was detectable. In line with the assumption that Se(-)-mice have an increased glucose turnover, Se(-)-mice exhibited a greater glucose tolerance when treated with an oral glucose load of 2.5 mg glucose/kg body weight. Also, the Se(-)-mice had a lower blood glucose level as compared to Se+-controls (89 +/- 3 versus 110 +/- 12 mg glucose/100 ml blood). Further in vitro experiments with red blood cells from Se(-)-mice showed that erythrocytes did not contribute to an increased CO2 formation from glucose via the pentose phosphate shunt. No significant differences between Se(-)- and Se+-animals were found in the profile of urinary metabolites, including ketone bodies and nitrogen excretion. These findings suggest a hitherto unknown involvement of selenium in specific regulatory sites of intermediary metabolism. PMID- 3113497 TI - Biological and immunological properties of zebra pituitary gonadotropins: comparison with horse and donkey gonadotropins. AB - Previous studies from this laboratory have described the properties of purified luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from horse and donkey anterior pituitary glands. The present study afforded the opportunity to further characterize these previously purified hormone preparations and to compare them with enriched gonadotropin fractions from zebra pituitary glands. Although a single LH and FSH fraction was usually obtained for each pool of pituitaries, two separate zebra LH and two donkey FSH preparations were generated. Purified hormone preparations from the horse were designated eLH and eFSH. Preparations zLH-A, zLH-B, and zFSH were obtained from zebra pituitaries, and fractions dLH, dFSH-A, and dFSH-B were prepared from donkey pituitary glands. These preparations were analyzed by LH and FSH radioimmunoassays (RIAs), radioreceptor assays (RRAs), LH bioassay, and chromatofocusing. Clear immunological differences were observed between equid gonadotropins. Homologous RIAs for eLH and eFSH did not cross-react similarly, or in a parallel fashion, with gonadotropins from the donkey and zebra. In contrast, RIAs capable of assessing LH or FSH in a wide number of species showed all equid gonadotropin preparations to have considerable activity and to produce parallel dilution curves. Relative to eLH (1.00), zLH-A was found to have higher LH bioactivity:LH RIA (2.50), LH RRA:LH RIA (1.42), and LH bioactivity: LH RRA (2.21) activity ratios. The dLH and zLH-B fractions only differed from eLH in LH RRA:LH RIA activity (0.69 and 0.62, respectively). Only LH from the horse possessed clear intrinsic FSH-receptor-binding activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113496 TI - Studies on the mechanism of Escherichia coli heat-stable enterotoxin-induced diarrhoea in mice. AB - The unidirectional fluxes of Na+, Cl- and Ca2+ and activities of calmodulin in the intestinal microvillar core were studied in Escherichia coli heat-stable enterotoxin-treated mice. There was net secretion of Na+ and Cl- in toxin-treated animals, while in control animals there was net absorption of these ions. In both control and experimental animals, there was net absorption of Ca2+; however, the absorption was significantly higher (P less than 0.01) in experimental animals when compared to controls. In the presence of Ca2+-ionophore, there was a net secretion of Na+ and Cl- in controls, while the Ca2+-ionophore could not cause any change in the fluxes of these ions in experimental animals. The activity of calmodulin was significantly higher (P less than 0.01) in experimental animals. Verapamil, a calcium channel blocker, and trifluoperazine, a calmodulin inhibitor, reversed the effects of Ca2+-ionophore and heat-stable enterotoxin. These studies demonstrate that the toxin acts through Ca2+-calmodulin, and secretion of Na+ and Cl- in experimental animals is due to an increase in calcium absorption and an increase in calmodulin activity in the intestinal microvillar core. PMID- 3113498 TI - Testicular compensatory hypertrophy in the hemicastrated calf: effects of exogenous estradiol. AB - Unilaterally orchidectomized (hemicastrated) bull calves were studied to monitor possible changes in serum concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) during the phase of testicular compensatory growth, to examine the characteristics of LH and FSH binding to the testis of the post pubertal animal, and to determine whether any of these responses were altered by exogenous estradiol. Twenty-four calves were assigned randomly at one week of age to a 2 X 2 factorial experiment involving intact control (I) and hemicastrated animals (H), as well as estradiol-implanted intact (I+E2) and hemicastrated animals (H+E2). Relative to I, testis growth was accelerated in H and suppressed in I+E2 and H+E2. Mean testis weights at 27 weeks of age were 42 +/- 4, 72 +/- 6, 12 +/- 1 and 14 +/- 1 g for the four respective treatment groups. Serum FSH, but not serum LH, was positively associated with the accelerated testis growth of H. LH and FSH binding per testis were both enhanced approximately twofold in the testis from hemicastrated animals relative to those from intact calves. In contrast, estradiol markedly suppressed the number of LH-binding sites per testis in both I and H calves, but only suppressed the number of FSH-binding sites per testis in H calves. LH-affinity constants were not affected by treatment, whereas those for FSH were significantly decreased by estradiol. In conclusion, neonatal hemicastration results in elevated serum FSH, testicular compensatory hypertrophy, and an increased number of gonadotropin receptors in the bovine testis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113499 TI - Regulation of hamster embryo development in vitro by carbon dioxide. AB - We have examined the effect of collecting and culturing hamster eight-cell embryos in media containing high levels of bicarbonate and/or CO2 on development in vitro. An approximate doubling in the percentage of embryos developing to the blastocyst stage was observed upon raising the concentration of CO2 in the gas phase from 5% to 10% CO2. Development to the blastocyst stage was not affected by the bicarbonate concentration (6-50 mM), nor by the pH of the medium (6.5-7.4). However, escape of embryos from their zonae pellucidae was pH-dependent (optimum pH 7.1-7.4). We hypothesized that the beneficial effect of high concentrations of CO2 on blastocyst development was due to the action of CO2 as a weak acid in regulating intracellular pH (pHi). To test this hypothesis, eight-cell embryos were cultured under 5% CO2 in media containing various concentrations of organic weak acids (lactic or acetic acids, or the non-metabolizable compound 2,4 dimethyloxazolidine-dione). Embryos cultured in standard medium (TALP) under 5% and 10% CO2 served as low and high controls, respectively. At optimum concentrations, all of the media containing weak acids supported embryo development significantly better than 5% CO2-equilibrated low control medium, and gave a response similar to that obtained with high control medium equilibrated in 10% CO2. These studies demonstrate that culture in a 10% CO2 environment has a marked stimulatory effect on in vitro development of hamster eight-cell embryos and suggest that this effect is due to maintenance of pHi. PMID- 3113500 TI - Pituitary gonadotropins, hypothalamic gonadotropin-releasing hormone, and testicular traits of boars exposed to natural or supplemental lighting during pubertal development. AB - Seventy crossbred boars were reared under natural (30 lux) or supplemental lighting (1000 lux) beginning at 4 wk of age. Boars received supplemental lighting from six 40-watt fluorescent bulbs between 0530 and 2030 h. Five boars from each treatment were killed at 67, 91, 119, 155, 182, 210, or 246 days of age. No differences (p greater than 0.05) in pituitary concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were found between treatment groups at any age. Total pituitary content of LH, FSH and PRL increased as boars became older, but when expressed as hormone concentration, only PRL increased with age. Content of gonadotropin-releasing hormone (GnRH) in the pituitary stalk-median eminence, preoptic area, and hypothalamus proper was similar (p greater than 0.05) between treatments. When GnRH contents were totaled and combined for the treatment groups, it was found that GnRH content increased (p less than 0.05) as boars became older. No differences (p greater than 0.05) were observed in testicular volume percentage of seminiferous tubules and tubular diameter between lighting treatments. These data demonstrate that the supplemental lighting does not influence puberty in boars by altering hypothalamic content of GnRH or pituitary stores of LH, FSH, and PRL. PMID- 3113501 TI - Endocrine responses in relation to compensatory testicular growth after neonatal hemicastration in boars. AB - Mass (TM) and relative mass (organ mass/body mass; RTM) of the right testis and epididymis (EM and REM, respectively) were determined every 14 days from 10 to 122 days of age for intact boars (I) and boars hemicastrated on Day 10 (HC) in two crossbred herds (Trial 1 and Trial 2). Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, growth hormone (GH), and testosterone were determined in four blood samples from each pig, three collected 24 h prior to castration and one immediately prior to castration. Values for TM and RTM of HC boars were approximately double (p less than 0.0001) those of I boars by 38 days of age, and these differences were maintained through Day 122. Both EM and REM were greater (p less than 0.05) in HC than in I boars from Day 52 to Day 122. The TM, RTM, EM and REM were greater (p less than 0.05) in Trial 1 than in Trial 2 for both I and HC boars from Day 80 to Day 122, indicating an earlier onset of pubertal testicular growth in the Trial-1 boars. Plasma GH concentration was greater (p less than 0.05) in HC than in I boars from Day 16 to Day 38. A transient increase in plasma FSH (p less than 0.05) was observed from Day 24 to Day 38. After Day 38, there was no difference (p greater than 0.05) in FSH or GH between HC and I boars, or between trials. Plasma LH, prolactin, and testosterone concentrations were also similar in HC and I boars.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113502 TI - Gonadotropin-releasing hormone treatment induces follicular growth and ovulation in seasonally anestrous mares. AB - A study was conducted to evaluate the effectiveness of gonadotropin-releasing hormone (GnRH) pulse infusion to stimulate follicular development and induce ovulation in seasonally anestrous standardbred mares. Seventeen mares were selected for use in this experiment, on the basis of a previous normal reproductive history, and were housed under a photoperiod of 8L:16D beginning one week prior to the start of the experiment (second week in January). Mares were infused with 20 micrograms (n = 7) or 2 micrograms (n = 6) GnRH/h, or were subjected to photoperiod treatment only (controls, n = 4). Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone did not vary, and neither significant follicular development nor ovulation was observed in any control mare throughout the experimental period (greater than 60 days). By contrast, both groups of GnRH-treated mares showed elevated serum concentrations of LH and FSH within one day after the start of infusion. Mares infused with 20 micrograms GnRH/h had at least one follicle greater than or equal to 25 mm in 7.4 +/- 1.3 (mean +/- SEM) days following the start of infusion, and ovulated in 12.0 +/- 0.7 days. In the 2-microgram-GnRH/h treatment group, a 25-mm follicle was detected in 5.7 +/- 0.7 days, and ovulation occurred after 10.0 +/- 0.3 days of infusion. Ovulation in every instance was followed by a functional luteal phase, as indicated by the profiles of progesterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113503 TI - An intractable, ovary-independent impairment in hypothalamo-pituitary function in the estradiol-valerate-induced polycystic ovarian condition in the rat. AB - A single injection of estradiol valerate (EV) produces anovulatory acyclicity and polycystic ovaries (PCO) in the rat. Basal serum luteinizing hormone (LH) concentrations are attenuated whereas serum follicle stimulating-hormone (FSH) concentrations are in the high normal range in these animals. Subsequent unilateral ovariectomy restores ovulatory cycles and normal histology in the remaining ovary without correcting the aberrant basal serum gonadotropin concentrations. This suggests that although the blocked surge mechanism is correctable, a second relatively intractable, ovary-independent impairment compromises basal gonadotropin production. To identify and characterize this second component, we have examined hypothalamic-pituitary function in PCO rats after bilateral ovariectomy. Adult (200-250 g), normal cyclic Wistar rats were injected with 2 mg EV or with vehicle (control). Nine weeks later all animals were ovariectomized and PCO was confirmed in the EV-treated animals. Animals were killed at 0, 2, 7, 14, and 28 days after ovariectomy, and hypothalamic content of luteinizing hormone-releasing hormone (LHRH) and pituitary and serum concentrations of LH and FSH were measured. LH and FSH responses to exogenous LHRH were assessed. Serum progesterone, testosterone, and estradiol concentrations were determined at 28 days. Hypothalamic LHRH decreased significantly in all animals over the 28-day period. Although LHRH values did not differ at Time 0, by 28 days there was significantly less LHRH in the hypothalami of control than in PCO rats. This pattern of depletion was mirrored by corresponding reciprocal patterns of increasing serum gonadotropin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113504 TI - The effects of progesterone on follicular growth in the rabbit ovary. AB - Studies were undertaken to measure the growth of follicles in the rabbit ovary during periods of elevated blood levels of progesterone. The progestin was increased in the blood by pregnancy or by implantation of progesterone pellets, which raised blood progesterone to near the levels measured during pregnancy. After 1, 2, 3, or 4 weeks of pregnancy or progesterone-pellet treatment, follicles of 1.0 mm external diameter or greater were dissected out of the ovaries and their external diameters were measured; then, each follicle was extracted for measurement of estradiol content. Blood levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in these animals as well. Follicles up to 2.5 mm in diameter were found in the ovaries of nonpregnant and untreated animals while 1.8 mm was the maximal size found during pregnancy or progesterone-pellet treatment. Furthermore, both in pregnant and in progesterone-treated rabbits, the follicular estradiol content and concentration were significantly suppressed compared to follicles from untreated rabbits. The progesterone pellets had no major effect on the levels of LH and FSH in the blood; the concentration of these gonadotropins in the progesterone-treated rabbits was virtually identical to levels previously measured in the blood of pregnant animals. The results of these studies indicate that progesterone exerts an inhibitory action on follicular development and steroidogenic function in the rabbit ovary. The progesterone action appears to be exerted directly on the ovary and is not indirect, by way of an inhibition of gonadotropin secretion. PMID- 3113505 TI - Systematic studies invalidate the neonatally androgenized rat as a model for polycystic ovary disease. AB - As an adult, the neonatally androgenized (AZ) rat is anovulatory and exhibits follicular cysts. Thus, the AZ rat has been used as a model for polycystic ovary disease (PCO). However, its correlation with the human disease is not clear; so we have studied the AZ rat to determine its suitability as a PCO model. In Experiment I, reproductive hormones were measured at specific intervals between postnatal Days 15 and 90 in saline-treated and AZ rats. In Experiment II, AZ rats were treated with exogenous follicle-stimulating hormone (FSH) or subjected to unilateral ovariectomy (ULO) as analogies to therapies that have been used to treat human PCO. The results demonstrate that the luteinizing hormone (LH), FSH, testosterone (T), and estradiol (E2) concentrations of the AZ rat were not different from control values. Additionally, FSH therapy did not increase the E2 concentrations or the ovarian weight of the AZ rat. Furthermore, control and AZ rats exhibited similar post-ULO rises in FSH, but compensatory ovarian hypertrophy was not evident in the AZ rat. We conclude that 1) the hormonal and morphological patterns observed in the AZ rat do not correlate with those of PCO and 2) the androgenized rat does not provide an adequate model to study PCO. PMID- 3113506 TI - Development of structural organization of protein-synthesizing machinery from prokaryotes to eukaryotes. AB - Though the mechanisms of protein biosynthesis are similar in the cells of prokaryotes and eukaryotes, the eukaryotic translational machinery in the cell is arranged more intricately. One of the most striking characteristic features of the eukaryotic translational machinery is that the eukaryotic proteins involved in the translational process, such as initiation factors, elongation factors and aminoacyl-tRNA synthetases, in contrast to their prokaryotic analogs, possess a non-specific affinity for RNA. Due to the RNA-binding ability, these eukaryotic proteins can be compartmentalized on polyribosomes. In addition to the proteins of the translational apparatus, several other eukaryotic RNA-binding proteins can be also compartmentalized on polyribosomes; these proteins include glycolytic enzymes, steroid hormone receptors and intermediate filament proteins. Thus, the eukaryotic polyribosome is an element of the cytoplasmic labile structure on which various proteins can be compartmentalized and, consequently, different biochemical pathways can be integrated. PMID- 3113507 TI - [Effect of the mode of extrapulmonary gas exchange on the function and metabolism of pulmonary surfactant]. AB - The peculiarities of the functional state of lung surfactant as well as the character and degree of disorders in its phospholipid metabolism during venoarterial perfusion and extrapulmonary 120-min oxygenation carried out with the help of contact-type (foam-film) and membrane ("Sever") oxygenators were studied in 28 experimental dogs. It was shown that the functional state and phospholipid metabolism of lung surfactant were strongly dependent on the mode of extrapulmonary gas exchange (the type of oxygenator). Membrane oxygenation is more physiological than contact-type gas exchange. The rise in ST min of bronchoalveolar wash-outs with the application of foam-film oxygenator to 25 mN/m and above is caused by disorders in phospholipid metabolism of lung surfactant. It is manifested in the decrease of phosphatidylcholine content, the increase in sphingomyelin, the appearance of lysophosphatidylcholine fraction and the decrease in phosphatidylcholine/sphingomyelin ratio. PMID- 3113508 TI - [Effect of verapamil on focal epileptic activity in the rat cerebral cortex]. AB - Experiments were carried out on 64 nonanesthetized male Wistar rats (200-220 g). Epileptic foci were induced by the application of a filter paper saturated with a solution of benzylpenicillin sodium salt (12,000 and 20,000 U/ml) to the sensorimotor cortex. It was shown that subsequent intraperitoneal administration of verapamil (5 mg/kg and 10 mg/kg) during steady focal epileptic activity (EpA) resulted in the suppression of EpA in most animals. The antiepileptic effect of verapamil was manifested in a reduced frequency and amplitude of spike discharges, decreased power of epileptic foci and less frequent appearance of seizure (ictal) discharges. The role of Ca canals of neuronal membranes in the pathogenesis of epilepsy is discussed. PMID- 3113509 TI - [Effect of calmidazolium (R 24571) on the electrical and contractile properties of smooth muscle cells in the guinea pig ureter]. AB - Calmidazolium in macromolecular concentrations inhibited the electric and contractile activity of smooth muscle cells (SMC). The concentrations causing a 50% inhibition of oscillations on the action potential (AP) plate were equal to 1 X 10(-6) microM, AP amplitude was 3 X 10(-6) microM and contraction amplitude was 1 X 10(-6) microM. Calcium ionophore A 23187/8 X 10(-7) microM, added to the normal Krebs solution, decreased rapid AP components amplitude and increased the contraction power of the isolated SMC strip by 62 +/- 9%. A 23187, though to a lesser extent, increased smooth muscle contractions during the action of calmidazolium. With combined use of A 23187 and calmidazolium, rapid AP components were depressed to a greater extent than each of them taken separately. The data obtained point to the presence of calmodulin or similar protein in SMC of the calcium channels. PMID- 3113510 TI - [Phases of the initial reaction of the sympatho-adrenal system to stress]. AB - Changes in the content and ratio of catecholamines, their precursors and metabolites in canine blood and tissues during the initial period of stress have been studied. A sharp increase in tissue adrenaline (A) and dopamine (DA) and a decrease in tissue noradrenaline (NA); decline in blood A and rise in blood NA; inhibition of monoamine oxidase activity and a fall in metanephrine and normetanephrine blood and tissue level have been demonstrated in the first phase of reaction developing right after exposure to stress. A sharp synchronous rise in A, NA and DA and a parallel increase in their metabolic intensity towards oxidative deamination and O-methylation have been found in the second phase of reaction that develops in 60 sec. The first phase of the reaction has been designated as dissociation phase of sympathoadrenal secretory synthetic activity, and the second phase was termed the phase of synchronous system activation. PMID- 3113511 TI - High serum interleukin-2 receptor levels are related to advanced disease and a poor outcome in childhood non-Hodgkin's lymphoma. AB - The clinical usefulness of serum interleukin-2 receptor (IL2R) measurements was determined in 59 children with non-Hodgkin's lymphoma (NHL) and six with B cell acute lymphoblastic leukemia (B-ALL). Levels of the receptor showed a clear relationship to disease stage, as follows: B-ALL greater than stage III or IV diffuse small noncleaved-cell NHL greater than stage III or IV lymphoblastic NHL greater than stage I or II NHL. Soluble IL2R levels were also closely correlated with serum lactic dehydrogenase levels (r = 0.7, P = .0001), a recognized indicator of tumor cell burden. Children with higher soluble IL2R levels (greater than 1,000 U/mL) were significantly more likely to fail treatment (P = .001), even when the analysis was limited to those with more advanced disease: stages III and IV NHL and B-ALL (P = .02). In a multivariate analysis, soluble IL2R level was found to have greater predictive strength than either serum lactic dehydrogenase level or disease stage. Thus, the measurement of soluble IL2R in children with NHL could be expected to improve existing methods of risk assignment in this disease. PMID- 3113512 TI - 111In-oxine platelet survivals in thrombocytopenic infants. AB - Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous 111In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the 111In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to-liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration. PMID- 3113513 TI - Induction of proliferation of B prolymphocytic leukemia cells by phorbol ester and native or recombinant interferon-gamma. AB - Phorbol ester phorbol myristate acetate (PMA) induces proliferation in nonmalignant human B cells and B cells from a patient with B prolymphocytic leukemia (B-PLL). Mitogen-free T cell-derived conditioned medium acts synergistically with PMA in inducing proliferation of B-PLL cells but does not enhance the PMA-stimulated outgrowth of nonmalignant B cells. Interleukin 2 (IL 2) has no effect on the outgrowth of B-PLL cells, and monoclonal antibodies against the IL-2 receptor do not influence the response to PMA and conditioned medium. Recombinant interferon-gamma (IFN-gamma), in contrast, is a potent enhancer of PMA-induced proliferation of B-PLL cells. With gel filtration techniques and with the use of anti-IFN-gamma antibodies, it is shown that IFN gamma in the conditioned medium is responsible for the observed increase in B-PLL cell proliferation. Preincubation of B-PLL cells with IFN-gamma induces responsiveness to PMA, whereas IFN-gamma alone had no effect on these cells when pretreated with PMA. The combined data show that, in the presence of PMA, native and recombinant IFN-gamma are growth factors for B cells from a B-PLL patient and that IL-2 is not involved in this process. PMID- 3113514 TI - Antiidiotypic IgG crossreactive with Rh alloantibodies in red cell autoimmunity. AB - IgG autoantibodies eluted from RBCs of antiglobulin positive normal blood donors contained at least two antibody populations, an IgG autoantibody (Ab 1), and an IgG population (Ab 2) that agglutinated RBCs coated with some Rh(D) alloantibodies. Eight of 24 autoantibody eluates tested agglutinated 3 of 10 anti Rh(D) sensitized RBCs. The agglutinating activity was inhibited specifically by preincubation of the autoantibody eluate with the reactive anti-D. The reaction did not require the Fc domain of the anti-Rh(D), since autoantibody eluates agglutinated RBCs coated with F(ab')2 prepared from the reactive anti-D sera. These findings indicate that the RBCs of some antiglobulin-positive blood donors contain an immunoglobulin auto-antiidiotype (Ab 2) against the RBC autoantibody (Ab 1) which is demonstrable through its cross-reactivity with selected Rh(D) alloantibodies. Identification of auto-antiidiotypes in RBC autoimmunity lends support to the idiotype-antiidiotype network hypothesis of immune regulation and is consistent with the bizarre and complex serology of autoimmune hemolytic anemia. The absence of clinical hemolysis in antiglobulin-positive normal blood donors suggests that immunoglobulin idiotype-antiidiotype interactions may play a role in modulating the effects of RBC autoimmunity. PMID- 3113515 TI - Extracellular matrix of cultured bovine aortic endothelial cells contains functionally active type 1 plasminogen activator inhibitor. AB - The extracellular matrix (ECM) of cultured bovine aortic endothelial cells (BAEs) was analyzed by immunoblotting and reverse fibrin autography and shown to contain type 1 plasminogen activator inhibitor (PAI-1). Most PAI-1 in the ECM formed complexes with exogenously added tissue-type plasminogen activator (tPA), demonstrating that this PAI-1 was functionally active. The resulting tPA/PAI-1 complexes were recovered in the reaction solution, indicating that the PAI-1 in such complexes no longer bound to ECM. The PAI-1 could not be removed by incubating ECM in high salt (2 mol/L NaCl), sugars (1 mol/L galactose, 1 mol/L mannose), glycosaminoglycans (10 mmol/L heparin, 10 mmol/L dermatan sulfate), or epsilon-aminocaproic acid (0.1 mol/L). However, PAI-1 could be extracted from ECM by treatment with either arginine (0.5 mol/L) or potassium thiocyanate (2 mol/L), or by incubation under acidic conditions (pH 2.5). ECM depleted of PAI-1 by acid extraction was able to bind both the active and latent forms of PAI-1. In this instance, most of the bound PAI-1 did not form complexes with tPA, indicating that the latent form was not activated as a consequence of binding to ECM. Although the PAI-1 activity in conditioned medium decayed with a half-life (t 1/2) of less than 3 hours, the t 1/2 of ECM-associated PAI-1 was greater than 24 hours. These data suggest that PAI-1 is produced by cultured BAEs in an active form and is then either released into the medium where it is rapidly inactivated or into the subendothelium where it binds to ECM. The specific binding of PAI-1 to ECM protects it from this inactivation. PMID- 3113516 TI - Abnormal stimulated adherence of neonatal granulocytes: impaired induction of surface Mac-1 by chemotactic factors or secretagogues. AB - To identify possible secretory determinants of impaired hyperadherence and stimulated migration of neonatal granulocytes (NGs), we performed correlative studies of: (a) specific granule content and exocytosis, (b) secretago-gue mediated upregulation of f-met-leu-phe (fMLP) receptors, (c) the chemotactic induction of the adhesive glycoproteins Mac-1 alpha (complement receptor 3) and beta, and (d) morphometric assessments of specific (peroxidase negative) granule depletion following chemotactic stimulation. Lactoferrin (LF) content of NG suspensions (cord blood or peripheral blood cells) was profoundly diminished (mean +/- SD 51% +/- 18% of normal) as compared with healthy adult granulocytes (AGs). Despite diminished cellular content, LF release by NG suspensions in response to fMLP was comparable to that of AGs. In contrast, LF release by NG suspensions was significantly diminished in response to phorbol myristate acetate (PMA) or calcium ionophor A23187 and/or during stimulated cell spreading, experimental conditions promoting overall greater LF depletion than chemotactic stimuli. In addition, NGs demonstrated an impaired capacity to upregulate fMLP receptors in response to PMA or A23187 when tested under the same experimental conditions. Baseline expression of the adhesive glycoproteins Mac-1 alpha and beta on NG surfaces was normal, but induction or upregulation of these proteins by chemotactic concentrations of fMLP, C5a as well as secretory (high) concentrations of PMA and A23187, was significantly diminished as compared with AGs. In contrast, chemotactic induction of the surface expression of the complement receptor-1 (CR-1) on NGs was normal. An impaired induction of Mac-1 alpha or beta was directly related to an impaired enhancement of adherence of NG in response to fMLP over a chemotactically relevant concentration range (10(-10) to 10(-7) mol/L). Moreover, in blocking-incubation experiments using anti-Mac-1 alpha/beta monoclonal antibodies (MAbs), significantly less inhibition of adherence by these MAbs was evident with fMLP-stimulated NG as compared with AG suspensions. Under selected chemotactic conditions, ultrastructural assessments of NGs demonstrated diminished peroxidase-negative granule loss in association with diminished granule-membrane fusion and the "addition" of plasma membrane. These studies suggest that abnormal expression of multiple surface determinants derived from peroxidase-negative granules or other intracellular pools may contribute to deficient chemotaxis or other inflammatory functions of NGs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3113517 TI - Selective uptake of [3H]arachidonic acid into the dense tubular system of human platelets. AB - We have used quantitative electron microscopic autoradiography to characterize the subcellular distribution of arachidonoyl phospholipids following brief (5 minutes) exposure of unstimulated human platelets to [3H]arachidonic acid. Labeled arachidonate was taken up rapidly and incorporated into phospholipids. Phospholipid radioactivity was preserved and spatially fixed during tissue processing for electron microscopy. Analysis of autoradiographs showed that following a brief exposure to 750 nmol/L [3H]arachidonate, there is selective labeling of an internal membrane compartment composed of the dense tubular system and the open canalicular system. The plasma membrane, platelet granules, and nonmembranous cytoplasm were not labeled. Since the open canalicular system is continuous with the plasma membrane and since phospholipids in continuous membranes are freely diffusible, our observations indicate that [3H]arachidonate was incorporated into phospholipids within the dense tubular system and not the open canalicular system. Thus, the dense tubular system, known to contain cyclooxygenase activity, incorporates arachidonate selectively following brief exposure to this fatty acid, presumably to concentrate it in proximity to enzymes for icosanoid synthesis. PMID- 3113518 TI - Does the CLL B lymphocyte correspond to expansion of an immature B clone or to expansion of a distinct subpopulation of B cells? AB - Most CLL cases correspond to proliferation of a B-cell clone characterized by (1) low amounts of SmIg, (2) the presence of receptors for mouse red blood cells, (3) the presence of a 67-kd antigenic determinant recognized by CD5 monoclonal antibodies, also present in normal T cells, (4) the ability of these cells to differentiate in vitro, and (5) the ability at least for some clones to differentiate and secrete immunoglobulins in vivo. The normal counterpart to this B-cell clone corresponds to a small subpopulation of lymphocytes, present at the edge of the germinal center in human lymph nodes. Interestingly, this subpopulation appears to constitute a substantial part of the B-cell population in 20-week-old fetal lymph nodes and spleen. These results have induced most authors to assume that the CLL B lymphocyte corresponds to proliferation of an immature B-cell clone, arrested at an intermediate stage between pre-B cells and mature B cells. However, this hypothesis does not explain the high frequency with which hypogammaglobulinemia and autoimmune hemolytic anemia are found in B CLL. In this work, we discuss the possibility that the CLL B lymphocyte corresponds to proliferation of a B-cell line, whose counterpart in the mouse is the Ly1 B, Lyb5+ subpopulation. PMID- 3113519 TI - Some aspects of the enzymic inactivation of sympathomimetic amines. AB - This review seeks to discuss the possible importance of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) in terminating the effects of released sympathetic transmitters and in the inactivation of endogenous or administered sympathomimetic amines with particular reference to some aspects of the cardiovascular system. Use of in vitro preparations of blood vessels and of other smooth muscles, such as vas deferens and anococcygeus, has thrown light on possible roles for these deaminating enzymes, even in the inactivation of noradrenaline, while the new reversible inhibitors of MAO-A show promise as antidepressants with a reduced risk of hypertensive crises following the ingestion of tyramine-containing food. However, the role of SSAO in the in inactivation of amines remains an enigma, even though much is now known of its biochemical nature. While the pharmacological responses to amine substrates can be potentiated by inhibition of SSAO, there is a suspicion that it is product rather than substrate that is more important. PMID- 3113521 TI - Diagnostic related groups: problems and opportunities. AB - Diagnostic Related Groups (DRGs) represent a paradox. On the one hand, they lack clinical meaningfulness, particularly in regard to cancer patients. DRG 403, which includes patients diagnosed than 69 and/or complications or comorbidities, is particularly inadequate as a tool to group together homogeneous patients. On the other hand, the practice of classifying similar patients into clinically meaningful groups represents a potentially valuable new tool for providing cost effective patient care. PMID- 3113522 TI - Valuing the man-sievert in X-ray diagnosis. AB - New advice from the National Radiological Protection Board gives a range of monetary values for the unit collective dose, depending in part on the annual individual dose. In this paper the special factors in medical radiodiagnosis are described and a valuation for the man-sievert in this field is suggested. The harm to children from ionising radiation may be appreciably larger than in adults, and a different value for children and in obstetrics is suggested. PMID- 3113520 TI - A monoclonal antibody to the heavy chain of human IgM with a particular reaction pattern in human B-cell malignancies. AB - We produced a monoclonal antibody to the human mu-chain. Its specificity was proved by amino acid-sequence analysis of immunoabsorbent purified cell surface antigen. In binding studies an affinity constant (K-aff) of 5.7 X 10(9) M-1 was determined. When compared with a polyclonal anti-IgM antiserum it was found that this antibody may react with a determinant of the mu-chain differently exposed in clonal B-cell disorders rendering it to a reagent of particular diagnostic interest. PMID- 3113523 TI - Balloon dilatation of bilharzial ureteric strictures. AB - Balloon dilatation was performed in nine patients with bilharzial ureteric strictures. In six patients a percutaneous, antegrade approach was used and in three a balloon catheter was introduced into the ureter via a cystoscope. In another four patients, negotiation of the strictured area with a guide wire failed. In all dilated patients, symptomatic and urographic relief of the obstruction was obtained during follow-up periods of 3 to 38 months (mean 19). One patient was re-dilated after 24 months and has remained symptom-free for a further 18 months. Balloon dilatation seems to be a promising method of treating this condition. PMID- 3113524 TI - Instillation of mitomycin C and doxorubicin in the prevention of recurrent superficial (Ta-T1) bladder cancer. AB - Both Mitomycin C (MMC) and doxorubicin (Adriamycin) (ADM) prevent the recurrence of superficial papillary (Ta-T1) urinary bladder cancers and also reduce the rate of progression. MMC appears to be more effective than ADM in buffered instillations. The number of recurrent tumours (RI/m) and the number of recurrence times (RR) before prophylactic instillation were of significant prognostic importance but the prognostic value of the grade was questionable. The buffer solution, together with methyl prednisolone, reduced the incidence of chemical cystitis. PMID- 3113525 TI - Carcinoma arising in posterior pharyngeal pulsion diverticulum (Zenker's diverticulum). AB - Carcinoma is a rare but recognized complication of posterior pharyngeal pulsion (Zenker's diverticulum). Such diverticula merit radiological and endoscopic examination before operation. Surgery is preferred to radiotherapy in the treatment of carcinoma, the choice of operation resting between one-stage diverticulectomy for cancer confined to the body of the sac and pharyngolaryngectomy for more extensive lesions. PMID- 3113526 TI - Duplex scanning of the internal carotid artery: an assessment of cerebral blood flow. AB - Duplex ultrasound scanning (B-mode imaging and pulsed Doppler shift analysis) was used to measure internal carotid artery blood flow (ICBF) in 20 volunteers. The effect of changes in end tidal CO2 on cerebral blood flow was measured. When corrected to a PCO2, of 40 torr (5.32 kPa) internal carotid artery blood flow was 286 +/- 16 ml min-1 (mean +/- s.e.m.). Specific CO2 reactivity (the change in flow per torr change in CO2) was 8.16 +/- 0.69 ml min-1 torr-1 which was equivalent to 2.0 +/- 0.1 per cent of the flow at 40 torr per torr change in CO2 (percentage CO2 reactivity). The mean value and the CO2 reactivity compare favourably with previously reported measurements by other techniques. These data suggest that the non-invasive measurement of internal carotid artery blood flow by Doppler ultrasound scanning is an assessment of cerebral blood flow that can be used to study both normal and pathological changes within the cerebral circulation. PMID- 3113527 TI - Model of TPN-associated hepatobiliary dysfunction in the young pig. AB - Gallbladder 'sludge' and cholestasis are two common complications associated with total parenteral nutrition (TPN), but the aetiology of each is uncertain. An animal model has been developed in the young pig which demonstrates these two complications. Five female piglets, of Landrace Large White Cross variety weighing 4.5-5.9 kg, received nutritional support for 2 weeks with a continuous infusion of TPN solution at a dose of 150 kcal kg-1 day-1. The solution was 35 per cent dextrose, 5 per cent L-amino acids with conventional electrolyte, mineral and vitamin additives. No lipid was used in the solution. Five weight matched animals were used as controls. All animals in the TPN group developed 'sludge' in their gallbladders, decreased basal bile flow, decreased bile salt excretion and a diminished response to bile salt stimulated bile flow, as compared with controls. There was no abnormality in routine liver function tests or liver histology. It is concluded that TPN therapy in this animal model is associated with the appearance of gallbladder 'sludge', and cholestasis as demonstrated by direct bile flow studies. It is suggested that this bile flow abnormality is due to a decrease in bile salt dependent and bile salt independent fractions of canalicular bile flow. The model provides the opportunity to investigate TPN related hepatobiliary dysfunction in an animal that has similar liver function to man and comparable nutritional requirements. PMID- 3113528 TI - Obstructing calculous material in a periampullary duodenal diverticulum associated with primary common bile duct calculi and acute pancreatitis. PMID- 3113529 TI - Microdiets: love them or leave them? PMID- 3113530 TI - Vena caval filters: keeping big clots down. PMID- 3113531 TI - Telling patients about their medicines. PMID- 3113532 TI - Genetic engineering and corneal grafting. PMID- 3113533 TI - Red cell antibodies. PMID- 3113534 TI - Acute renal failure: diagnosis of cause needed within hours. PMID- 3113535 TI - Nuclear magnetic resonance imaging. PMID- 3113536 TI - Reduction in postprandial energy expenditure during pregnancy. AB - Energy expenditure was measured during pregnancy in seven primigravid women at 12 15, 25-28, and 34-36 weeks and after the cessation of lactation. On each occasion the resting metabolic rate and the increase in metabolic rate after ingestion of a liquid test meal were measured by indirect calorimetry. In absolute terms the resting metabolic rate increased steadily during pregnancy but when expressed per unit of body weight no change was found. The energetic response to a mixed constituent meal was significantly reduced by 28% in the middle trimester of pregnancy. These findings suggest a possible maternal adaptation to increase energetic efficiency at a time when the energy demands of the fetus are high. PMID- 3113538 TI - Is screening for bacteriuria in pregnancy worth while? AB - A total of 4470 pregnant women were screened for bacteriuria by the dipslide method and significant growth found in 226 (5.1%). In 198 cases the urine was re examined, in 119 by using suprapubic aspiration or catheterisation (62 (52%) samples contained bacteria) and in 79 by using midstream urine samples (26 (33%) samples contained greater than 10(8) colony forming units/1), showing the maximum prevalence of confirmed bacteriuria to be 2.6%. Overt urinary tract infection developed later in four of 80 patients with proved bacteriuria who had been given antibiotics, in one of eight untreated patients with bacteriuria, in one of 110 patients with unconfirmed bacteriuria, and in one of 226 non-bacteriuric controls. A history of urinary tract infection was given by 18% of controls and 42% of women with confirmed bacteriuria. Screening for bacteriuria and treatment with antibiotics to prevent later overt infection is expensive. Whether it is worth while and cost effective depends largely on the prevalence of bacteriuria in the local population and the proportion who develop overt infection. The screening and treatment programme reported here appeared to prevent only six cases of overt infection. PMID- 3113537 TI - Deoxyribonucleic acid polymorphism of the apoprotein AI-CIII-AIV gene cluster and coronary heart disease in non-insulin-dependent diabetes. AB - The prevalence of an uncommon allelic variant (S2) of the apoprotein AI-CIII-AIV gene cluster was determined in non-insulin-dependent diabetics with or without evidence of coronary heart disease and in controls. Frequencies of the S2 allele were 14% for diabetics with coronary heart disease compared with 2% for non diabetics with no clinical evidence of occlusive vascular disease. No subject with the S2 allele was detected among a further group of matched diabetics without clinical features of macrovascular disease. The results suggest that a genetic component contributes to the susceptibility to coronary heart disease in non-insulin-dependent diabetics. Whether the observed deoxyribonucleic acid variant is aetiological for atherosclerosis or in linkage disequilibrium with other atherogenic loci on chromosome 11 remains to be clarified. PMID- 3113539 TI - Contamination of dropper bottles with tear fluid in an ophthalmic outpatient clinic. PMID- 3113540 TI - Limitations of direct ophthalmoscopy in screening for glaucoma. PMID- 3113541 TI - Changes in serum lipid concentrations during first 24 hours after myocardial infarction. PMID- 3113542 TI - Severe rectal bleeding due to Salmonella paratyphi B. PMID- 3113543 TI - Problems of comprehensive shared diabetes care. AB - In its first year 747 diabetics were entered into a comprehensive shared care scheme in which general practitioners agreed to follow up their own patients. After two years patients were recalled to hospital for review through a computer based recall system. Analysis of the first 209 patients reviewed showed that the recall system worked well with failure to trace only eight patients. Six new cases of foot ulcer, 15 of retinopathy, 14 of macular degeneration, and 15 of raised blood pressure requiring treatment were detected at review. Sixty four patients appeared to have had no check on their diabetes during the two years. Of the 117 with written evidence in their cooperation books that they had received some diabetic supervision, many had had no measurement of weight (32), blood pressure (49), or urine (68) or blood glucose (70), and only 55 had had foot and 65 eye examination. This erratic and generally poor standard of supervision suggests that much tighter organisation is required within each practice, with time being set aside specifically for care of diabetics. Practice nurses could have an important role in the delivery and organisation of care. PMID- 3113544 TI - Clinical epidemiology, not seroepidemiology, is the answer to Africa's AIDS problem. PMID- 3113545 TI - Prospective study of clinical, laboratory, and ancillary staff with accidental exposures to blood or body fluids from patients infected with HIV. AB - In a prospective study of 150 health care workers in the United Kingdom who had been accidentally exposed to the human immunodeficiency virus no evidence of transmission was found. Larger studies in the United States and anecdotal accounts in publications from other countries confirm that the risk of occupational infection is very low. Health care workers must adopt safe procedures at all times, however, to avoid exposure to infection. PMID- 3113547 TI - What is a good consultant? As the junior doctor sees it. PMID- 3113546 TI - Medical malpractice in perspective. II--The implications for Britain. AB - The "malpractice crisis" in the United States cannot be understood in isolation. Litigation is precipitated by features of the American health care and social security systems. Relative to the United Kingdom, there are fewer barriers of access to the courts, although the role of contingency fees has probably been exaggerated. Given the great institutional differences between the UK and the USA, the crisis seems unlikely to be replicated here unless there are further moves towards privatising both the costs of providing health care and the costs of its failures. It is concluded that a marginal change in the frequency or average cost of claims could have a serious impact on National Health Service resources, the medical defence societies, recruitment to specialties, and clinical practice. Debate over possible reforms is compromised by the dearth of good empirical data. Any changes, however, must address both the deterrence of bad practice and the compensation of injured patients. PMID- 3113548 TI - ABC of AIDS. The virus and the tests. PMID- 3113549 TI - Obstructive sleep apnoea and tonsillar lymphoma. PMID- 3113550 TI - Delayed cerebellar ataxia: a new complication of falciparum malaria? PMID- 3113551 TI - Treating Paget's disease. PMID- 3113552 TI - The unacceptable face of tipping. PMID- 3113553 TI - Hyposensitisation. PMID- 3113554 TI - Bicycle accidents in childhood. PMID- 3113555 TI - Standards for blood pressure measuring devices. PMID- 3113556 TI - Management tensions in laboratories. PMID- 3113557 TI - Video recording and child abuse. PMID- 3113558 TI - Penetrating cardiac injuries. PMID- 3113559 TI - McKeown reassessed. PMID- 3113560 TI - Aetiology of acute appendicitis. PMID- 3113561 TI - Imaging pulmonary arteriovenous malformations. PMID- 3113562 TI - The BMA's priorities. PMID- 3113563 TI - School dinners. PMID- 3113564 TI - Deux chevaux, Jaguar--or Ford. PMID- 3113565 TI - Apnoeic episodes induced by smothering: two cases identified by covert video surveillance. AB - Recurrent cyanotic episodes associated on some occasions with loss of consciousness due to cerebral hypoxia were investigated by long term tape recordings of breathing activity, oxygen saturation, air flow, electrocardiographic activity, and in some cases electroencephalographic activity. In 51 infants and children the mechanisms for the cyanotic episodes were identified (prolonged expiratory apnoea in 45, sleep related airway obstruction in three, seizure induced apnoea in one, behaviour induced apnoea in one). In one child apnoea was suspected as being caused by suffocation (smothering) by the mother. This was confirmed after enlisting the help of the police, who undertook covert video surveillance during cyanotic episodes. Each cyanotic episode was associated with a pattern of disturbance on the multichannel tape recordings which may be pathognomonic of this type of apnoea. A second infant with cyanotic episodes in whom smothering was suspected was referred for similar investigation after the availability of video recordings became established. Maternal smothering was again supported by specific patterns on multichannel tape recordings and confirmed by video surveillance. Diagnosis by video surveillance produces unequivocal evidence in these cases and avoids the need for medical and nursing staff to confront the mother with a possibly incorrect suspicion or in a court of law. PMID- 3113566 TI - Third trimester placental grading by ultrasonography as a test of fetal wellbeing. AB - In a study of 2000 unselected pregnant women the development of a mature placental appearance (grade 3) on ultrasonography by 34-36 weeks' gestation, observed in 15% of cases, was associated with maternal smoking, low parity, low maternal age, and being white. These women had an increased risk of problems during labour and their babies had an increased risk of low birth weight, poor condition at birth, and perinatal death. The women were randomly allocated to two groups: in one group the result of the placental grading was reported to the clinician responsible for care; in the second the result was noted but not reported. There was a significant decrease in the risk of perinatal death in the group where the grading was known. This reduction was responsible for a difference in the principal outcome index, a heterogeneous group of measures of mortality and morbidity, but this difference was not significant. This study alone does not justify routine late scanning, and further, larger trials are required. Nevertheless, the results do provide a basis for the reporting of placental grading when ultrasound examination is performed during the third trimester. PMID- 3113567 TI - Delivery after caesarean section: review of 2176 consecutive cases. AB - A total of 2176 consecutive patients who had had one previous caesarean section were studied retrospectively. A repeat elective caesarean section was performed in 395 (18.2%). Labour started spontaneously in 1363 patients, 301 of whom were given oxytocin to accelerate inert labour, and was induced by amniotomy and infusion of oxytocin in 418 women; 1618 of these 1781 patients (90.8%) delivered vaginally. Patients who had had a previous vaginal delivery were more likely to deliver vaginally again. Those women in whom the initial caesarean section had been performed during labour before the cervix was 4 cm dilated were less likely to deliver vaginally than those who had progressed further in labour or those who had had an elective caesarean section. Similarly, those who received oxytocin to stimulate inert labour were more likely to require a repeat caesarean section than those who did not. The uterine scar ruptured in only eight (0.45%) of the 1781 patients allowed into labour. The risk of rupture of the scar was not increased by the use of oxytocin alone either to induce or to accelerate labour. The combination of oxytocin to accelerate labour and epidural analgesia to provide pain relief, however, was associated with an increased incidence of scar rupture. Labour may be safely allowed in women who have had a previous caesarean section, most of whom will deliver vaginally. Induction of labour does not increase the risk of either a repeat caesarean section or rupture of a uterine scar. PMID- 3113569 TI - Proteinuria: value as predictor of cardiovascular mortality in insulin dependent diabetes mellitus. AB - The relation between diabetic microangiopathy and macroangiopathy was studied by analysing the relative mortality from cardiovascular disease in patients with insulin dependent diabetes mellitus with and without persistent proteinuria. The study group comprised 2890 diabetics diagnosed between 1933 and 1972 before the age of 31, and the study was conducted by using the linear logistic discrete failure time model. In patients with proteinuria the relative mortality from cardiovascular disease was 37 times that in the general population; in patients without proteinuria it was 4.2 times that in the general population. In both groups women had a relative mortality twice to 2.6 times that of men. In neither group was relative mortality correlated with duration of diabetes, suggesting that the association between diabetes and cardiovascular disease may be conferred by factors other than hyperglycaemia and hyperinsulinaemia. The high relative mortality from cardiovascular disease in diabetics with proteinuria indicates a strong association between diabetic microangiopathy and macroangiopathy, suggesting a common (pathogenetic?) mechanism for these two late diabetic complications. PMID- 3113570 TI - Oesophageal pain exacerbated by propranolol. PMID- 3113568 TI - Influence of proteinuria on vascular disease, blood pressure, and lipoproteins in insulin dependent diabetes mellitus. AB - Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria -mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval 0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism. PMID- 3113571 TI - Hypoglycaemia in insulin dependent diabetics: is advice heeded? PMID- 3113572 TI - Possible reactivation of hepatitis D with chronic delta antigenaemia by human immunodeficiency virus. PMID- 3113573 TI - Loin pain and haematuria syndrome: possible association with intrarenal arterial spasms. PMID- 3113574 TI - Changing incidence of non-accidental injury to children in South Glamorgan. PMID- 3113576 TI - Minimising bruising in the antecubital fossa after venepuncture. PMID- 3113575 TI - Fatal bronchospasm after topical lignocaine before bronchoscopy. PMID- 3113577 TI - Medical stereotypes and medical realities. PMID- 3113578 TI - Prospective study of symptoms and signs in acutely ill infants in general practice. AB - A study was made of all cases of acute illness in infants aged 6 months or less presenting in a Gosport practice over five months. The frequency in these patients of the well defined symptoms and signs suggested to be important by the preliminary report of the Department of Health and Social Security's multicentre study of postneonatal mortality was recorded. During the study period there were 161 infants of this age in the practice, who gave rise to 69 consultations with acute illness. Thirty eight of these were given drug treatment and five were referred to a paediatric unit, one of them on social grounds. There were no infant deaths in the practice (total population 11,400), but two occurred in the Gosport area (total population 83,000). It would be unrealistic to refer all patients with any one of the symptoms and signs, even when well defined, in the age group 6 months or less. Analysis of the symptoms and signs found in those children who required admission did not show any pattern differentiating them from those who did not. Although the symptoms and signs studied are of value in assessment and should be sought in these patients, they cannot be used singly or in any pattern to indicate referral per se. PMID- 3113580 TI - After safe sex, safe surgery? PMID- 3113579 TI - Manchester air disaster. AB - On 22 August 1985 a fire occurred on a Boeing 737 jet airliner at take off at Manchester Airport. One hundred and thirty seven passengers and crew were on board. Fifty two passengers died on the aircraft, 85 escaped. Most survivors had minor physical injuries, but 15 required admission to hospital because of smoke inhalation and two of these had severe burns. At presentation only one survivor required ventilation but within 12 hours a further five required ventilation. Although initially patients suffering from smoke inhalation may seem relatively well, lung function may deteriorate rapidly in the first 24 hours. Careful organisation and regular practice of procedures to deal with a major accident are essential to be able to respond adequately to such an event. PMID- 3113581 TI - What is a good consultant? When you have a terminal illness. PMID- 3113582 TI - Doctor, soldier, scientist, and shikari (H.E. Shortt). PMID- 3113583 TI - ABC of AIDS. Counselling. PMID- 3113584 TI - AIDS and medical confidentiality. AB - In summary, I have argued that the arguments offered or hinted at in favour of doctors' breaking medical confidentiality by passing on information about their patients' HIV state to others, including other doctors, when this is against the patient's considered wishes are generally unconvincing. Although in highly exceptional cases there may be justifications for overriding confidentiality, the requirement of medical confidentiality is a very strong, though not absolute, obligation. Patients, their contacts, doctors and their staff, and the common good are most likely to be best served if that tradition continues to be honoured. PMID- 3113585 TI - Testicular torsion in older men. PMID- 3113586 TI - Cervical smears: new terminology and new demands. PMID- 3113587 TI - Carcinoma of the cervix in young women. PMID- 3113588 TI - Surrogacy. PMID- 3113589 TI - Early versus late induction of labour in post-term pregnancy. PMID- 3113590 TI - Evaluation of portable haemoglobinometer in general practice. PMID- 3113591 TI - Ruptured abdominal aortic aneurysm presenting with ureteric colic. PMID- 3113592 TI - Housing conditions and ill health. PMID- 3113593 TI - Subcutaneous or intravenous heparin for deep vein thrombosis. PMID- 3113594 TI - The OPCS: many (more) happy returns? PMID- 3113595 TI - Osteoporosis, falls, and age in fracture of the proximal femur. AB - The relative importance of osteoporosis and risk of falling in causing hip fracture is not known. Femoral neck bone mass was measured in 708 elderly people, all of whom had fallen and injured a hip. Below 75 years of age there was a steep increase in relative risk of fracture with reduced bone mass, measured by Singh grade. Above that age the increase in risk was small, and neuromuscular responses which protect the skeleton against trauma may be more important than bone mass. PMID- 3113596 TI - Measles in children who have malignant disease. AB - A review study examined the clinical course of measles diagnosed in children being treated for malignant disease in Newcastle upon Tyne during 1973-86. Of the 17 cases diagnosed, five were fatal. Factors associated with a favourable outcome were a typical rash and Koplik's spots, which were accompanied by a detectable serum antibody response and the disappearance of measles giant cells from nasopharyngeal secretions. Pneumonitis severe enough to require assisted ventilation was invariably fatal. Pneumonitis and encephalitis were the main complications. Treatment included immunoglobulin, interferon, and ribavirin, but none could clearly be shown to be effective. The comparatively low mortality in this series may have been due to the extensive use of the fluorescent antibody technique in Newcastle during the study period and therefore detection of less severe cases as compared with other reports. PMID- 3113597 TI - Mortality and morbidity caused by measles in children with malignant disease attending four major treatment centres: a retrospective review. AB - Measles is a major cause of mortality and morbidity in children receiving treatment for leukaemia. A review was made of all the documented cases of measles in children in first remission from acute lymphoblastic leukaemia at four major treatment centres in 1974-84. Over the 11 years reviewed 1043 children with acute lymphoblastic leukaemia were referred to these centres. Fifty one (4.9%) died while in first remission and 15 (29.4%) of these deaths were due to measles or its complications: 12 cases of pneumonia, 10 of them fatal; and six cases of encephalitis, five of them fatal and the sixth child left severely handicapped. These children would have had at least a 50% chance of long term survival. The severity of measles in the immunocompromised patient reinforces the need to improve the poor uptake of measles immunisation in Britain. PMID- 3113598 TI - Measles must go and with it rubella. PMID- 3113599 TI - Live measles vaccine: a 21 year follow up. AB - 21 years after receiving Schwartz strain live measles vaccine 4500 trial participants showed a continuing high level of protection compared with those who were unvaccinated. Over the last seven years of the follow up no cases of measles were reported in vaccinated participants who had had close contact with the disease. Immunity induced by the vaccine seems to survive the challenge of close contact with measles in young children, even after 21 years. PMID- 3113600 TI - Cyst infection in acquired renal cystic disease. PMID- 3113601 TI - Neonatal respiratory distress caused by aspiration of a vaginal tablet containing prostaglandin. PMID- 3113602 TI - Care for patients with HIV infection and AIDS. PMID- 3113603 TI - Lymphoedema of the arm. PMID- 3113604 TI - What makes a good consultant? A GP's view. PMID- 3113605 TI - ABC of AIDS. Control of infection policies. PMID- 3113606 TI - Benoxaprofen case makes legal history. PMID- 3113607 TI - Advances in managing childhood cancer. PMID- 3113608 TI - Portraits from memory. 16--Muriel Robertson, FRS (1883-1973). PMID- 3113609 TI - Africa's AIDS problem. PMID- 3113610 TI - Diagnosing pulmonary thromboembolism. PMID- 3113611 TI - Exaggerated postural vasoconstrictor reflex in Raynaud's phenomenon. PMID- 3113613 TI - Special units for acute upper gastrointestinal bleeding. PMID- 3113614 TI - Asymptomatic carotid stenosis: spare the knife. PMID- 3113612 TI - Health and efficiency. PMID- 3113615 TI - Management of Parkinson's disease. PMID- 3113617 TI - The future role of midwives. PMID- 3113616 TI - Does atenolol have an effect on calcium metabolism? PMID- 3113618 TI - Pinch skin grafting or porcine dermis in venous ulcers. PMID- 3113620 TI - Drinking and driving: success of random breath testing in Finland. AB - Since the introduction of random breath testing in Finland in 1977 the drinking and driving rate has halved, and there has been an appreciable reduction in the rates of death and injury from road accidents associated with drinking. The results of Finnish studies indicate that random breath testing deters social drinkers and detects problem drinkers. Problem drinkers are more likely to be driving in morning traffic, when vulnerable road users such as children are about, and are more likely to be detected by random breath testing than by any other police activity. Random breath testing is a popular measure and has not only saved lives but has paid for itself by savings in health service and other resources. Introducing random breath testing into Britain could save at least 400 lives a year. The main recommendation of the Blennerhassett report of 1976- discretionary testing--is compared with the success of random breath testing in Finland. PMID- 3113619 TI - Is changing hypothalamic activity important for control of ovulation? AB - The activity of the hypothalamic gonadotrophin releasing hormone pulse generator in women with regular ovulatory and anovulatory menstrual cycles was assessed to see whether changes therein are important determinants of normal and impaired ovarian function. Endogenous gonadotrophin releasing hormone secretion was inferred by measurement of the pituitary luteinising hormone response by characterisation of pulsatile luteinising hormone release over eight hours on three occasions during the course of follicular development and once during the luteal stage of the same cycles. In 13 ovulatory cycles (serum progesterone concentration greater than 25 nmol/l) confirmed by ovarian ultrasonography a pronounced variability in luteinising hormone pulse patterns among subjects was compatible with ovulation. In the luteal stage of ovulatory cycles the luteinising hormone interpeak interval (85 min, range 42-125) was significantly longer than that during the early follicular (64 min, 40-103), mid-follicular (62 min, 37-107), and late follicular (59 min, 39-80) stages of the same cycles. Thus in ovulatory cycles no increase in frequency of the gonadotrophin releasing hormone pulse generator was detected during follicular development, though this activity decreased in the luteal stage. In five late follicular stage studies in which part of the preovulatory luteinising hormone surge was captured no change in pulse frequency of luteinising hormone was detected compared with the mid follicular stage of the same cycles or when compared with the late follicular stage of other cycles when no luteinising hormone surge was captured. Though mean luteinising hormone concentrations in luteinising hormone surge series (36 IU/l) were high, the amplitude of luteinising hormone pulses (165%) was only slightly greater than during non-surge late follicular stage studies (145%). Hence no change in hypothalamic gonadotrophin releasing hormone activity is required to generate the preovulatory discharge of luteinising hormone in man, which occurs as a result of the sensitising action of rising oestradiol concentrations on pituitary responsiveness to the same hypothalamic input signal. Luteinising hormone pulse frequency, peak amplitude, and mean serum luteinising hormone concentrations in seven anovulatory cycles (progesterone concentration less than 10 nmol/l) were not different from those at comparable stages of ovulatory cycles. These data suggest that the primary abnormality in this group of regularly menstruating anovulatory women lies in the ovary rather than in the hypothalamic control of the anterior pituitary. PMID- 3113621 TI - ABC of AIDS. Nursing care. PMID- 3113622 TI - What is a good consultant? A worm's eye view. PMID- 3113623 TI - Portraits from memory. 17--Sir Walter Russell Brain, FRS, PRCP (later Lord Brain). PMID- 3113624 TI - Incidence of unsuspected fractures in traumatic effusions of the elbow joint. PMID- 3113625 TI - Suffocation and videos. PMID- 3113626 TI - Halothane hepatitis in children. PMID- 3113627 TI - ABC of AIDS: neurological manifestations. PMID- 3113628 TI - Not all travellers need immunoglobulin for hepatitis A. PMID- 3113629 TI - Infantile apnoea and home monitoring. PMID- 3113630 TI - Infection by airborne Chlamydia trachomatis. PMID- 3113631 TI - Penetration of antibiotics into the respiratory tract. PMID- 3113633 TI - General practice consultations. PMID- 3113632 TI - Successful treatment of asymptomatic endometriosis: does it benefit infertile women? PMID- 3113634 TI - Refusal to treat AIDS and HIV positive patients. PMID- 3113635 TI - Persistent mesenteric ischaemia in a young woman. PMID- 3113636 TI - Refining thinking on type A behaviour and coronary heart disease. PMID- 3113637 TI - Resuscitating resuscitation. PMID- 3113639 TI - Surgery of morbid obesity. PMID- 3113638 TI - Coventry: a no drinking-driving city by the year 2000? PMID- 3113640 TI - A shocking American report with lessons for all. PMID- 3113641 TI - AIDS: a faltering step. PMID- 3113642 TI - How much energy does the breast fed infant consume and expend? AB - Energy intake in breast fed infants is uncertain. The doubly labelled water method was used to measure, simultaneously and non-invasively, energy expenditure, energy intake, milk volume intake, energy deposition, and the energy content of breast milk in 12 "free living" breast fed babies at 5 and 11 weeks of age. The validity of this new approach was assessed in a parallel study in 12 formula fed infants. The babies who were exclusively breast fed expended 1.28 and 1.68 MJ/day at five and 11 weeks and had intakes of 1.81 and 2.22 MJ/day; these intakes were associated with normal growth but were well below those recommended previously. At five and 11 weeks the calculated energy content of breast milk was 0.24 and 0.25 MJ/100 ml, which is substantially lower than that commonly reported in milk obtained unphysiologically by expression of the breast. These data cast doubt on the widely used published standards for infant feeding. PMID- 3113644 TI - Alcohol consumption and the risk of alcohol related cirrhosis in women. AB - The risks in women of cirrhosis with a likely primary alcohol aetiology were estimated for various levels of alcohol consumption in a case-control study. Data were obtained from 41 women with a first diagnosis of cirrhosis who had no evidence of non-alcohol-related cirrhosis; three matched controls were interviewed for each case. Significant increases in the risk of cirrhosis were detected at levels of consumption between 41 and 60 g daily; above this level a dose-response relation was observed. The risk of cirrhosis did not appear to be influenced by other nutritional factors or history of liver disease or use of hepatotoxic drugs. One per cent of Australian women consume more than 40 g alcohol daily, yet more than 90% of women identified with cirrhosis consumed alcohol at this level. Preventive interventions to reduce alcohol consumption in the small group of women who consume more than 40 g daily have the potential to reduce substantially the incidence of alcohol related cirrhosis. PMID- 3113643 TI - IgA-antigliadin antibodies in IgA mesangial nephropathy (Berger's disease). AB - Circulating IgA-antigliadin antibodies were detected with enzyme linked immunosorbent assay (ELISA) in four of 121 patients (3%) who had IgA mesangial nephropathy and 14 of 17 children (82%) who had untreated coeliac disease. No positive cases were present in the 54 healthy subjects of the control group. Three patients who had IgA nephropathy and IgA-antigliadin antibodies underwent jejunal biopsy, and two showed mucosal atrophy. In these two patients urinary abnormalities, together with the IgA-antigliadin antibodies, disappeared completely after three months and five months, respectively, of following a gluten free diet. Circulating IgA immune complexes were found in most patients who had coeliac disease and Berger's disease associated with IgA-antigliadin antibodies, suggesting overactivity of the B cells producing IgA in both conditions. By contrast, a circulating IgA rheumatoid factor was detectable in three of the four patients who had IgA nephropathy and asymptomatic coeliac disease but was always absent in children who had coeliac disease but did not show signs of renal disease. These results suggest that a more complex abnormality in the IgA immune response is necessary for renal disease to become manifest in patients who have gluten enteropathy. PMID- 3113645 TI - Death rates from stroke in England and Wales predicted from past maternal mortality. AB - Geographical differences in maternal mortality in England and Wales during 1911-4 correlate closely with death rates from stroke in the generation born around that time. The geographical distribution of stroke is more closely related to past maternal mortality than to any leading cause of death, past or present, except ischaemic heart disease, for which correlation coefficients with stroke are similar. This relation is new evidence that poor health and physique of mothers are important determinants of the risk of stroke among their offspring. PMID- 3113647 TI - Lethal malformations and perinatal mortality: a 10 year review with comparison of ethnic differences. AB - During 1976 to 1985 perinatal mortality in Leicestershire decreased from 21 to 9.5 per 1000 births. Throughout this period the incidence of lethal malformations, excluding neural tube defects, remained relatively constant at around 1.8 per 1000 births. Analysis of the malformations present in 201 lethally malformed babies showed that 147 (73%) had a disorder carrying a recurrence risk of 1% or greater. Only 7% of these malformations might have been predicted from the family history or advanced maternal age. The incidence of lethal malformations was significantly increased in the Asian population, largely because of an excess of autosomal recessive disorders. The contribution of lethal malformations to perinatal mortality has almost doubled over the past 10 years and is likely to increase despite prenatal diagnosis and improvements in obstetric and paediatric services. PMID- 3113646 TI - Type A behaviour and ischaemic heart disease in middle aged British men. AB - The Bortner questionnaire, which measures aspects of type A (coronary prone) behaviour was completed by 5936 men aged 40-59 selected at random from one general practice in each of 19 British towns. The presence of ischaemic heart disease was determined at initial examination and the men were followed up for an average of 6.2 years for morbidity and mortality from myocardial infarction and for sudden cardiac death. Non-manual workers had significantly higher scores (more type A) than manual workers and the score decreased (less type A) with increasing age. After adjustment for social class and age men with higher scores had higher prevalences of ischaemic heart disease less marked for electrocardiographic evidence and more marked for response to a chest pain questionnaire (angina or possible myocardial infarction). A man's recall of a doctor's diagnosis of ischaemic heart disease, however, did not relate to his Bortner score. There was no significant relation between the Bortner score and the attack rate or incidence of major ischaemic heart disease events. In this study type A behaviour, as measured by the Bortner questionnaire, did not predict major ischaemic heart disease events in British middle aged men. PMID- 3113648 TI - Prognosis of subsequent pregnancies after recurrent spontaneous abortion in first trimester. AB - The outcome of subsequent pregnancies was studied in 24 women with a history of three or more consecutive spontaneous abortions in the first trimester. Twenty one of the women agreed to forgo active treatment during the study period and three received progestogens or surgical intervention. As the outcome of their first pregnancy after recurrent abortion 18 of the 24 women delivered a liveborn infant after 28 weeks or more. Of all 49 pregnancies in the untreated group during the study, 10 ended in abortion. Only one woman in the study failed to achieve a live birth. Except in exceptional cases encouraging women with recurrent abortion to keep trying for a successful outcome is just as effective as currently recommended treatments. PMID- 3113650 TI - Safety and acceptability of condoms for use by homosexual men as a prophylactic against transmission of HIV during anogenital sexual intercourse. PMID- 3113649 TI - Endoscopic injection of alcohol for bleeding from gastroduodenal vascular anomalies. PMID- 3113651 TI - Alcohol and death certification: a survey of current practice and attitudes. PMID- 3113652 TI - Doctors have no time for alcohol screening. PMID- 3113653 TI - Successful treatment of infertility due to polycystic ovary disease using a combination of luteinising hormone releasing hormone agonist and low dosage menotrophin. PMID- 3113654 TI - Simultaneous primary infection with varicella zoster and Epstein-Barr viruses. PMID- 3113655 TI - Delusional depression after infectious mononucleosis. PMID- 3113656 TI - Unorthodox internal fixation of bone lesions in myelomatosis. PMID- 3113657 TI - Create and maintain an age-sex register. PMID- 3113658 TI - Retinal afferent and efferent connections in congenitally monophthalmic chicks. AB - The visual projections of the remaining eye of posthatch congenitally monophthalmic chicks were examined using wheat germ agglutinin-horseradish peroxidase. The morphology of the primary visual centres and their retinal projections contralateral to the injected eye were similar to those of normal chicks. The ipsilateral primary visual centres were smaller and less organized, yet all received retinal input. These ipsilateral retinal projections differ from those found in normal posthatch chicks [O'Leary et al.: Devl. Brain Res. 10: 93 109, 1983] in that they are more extensive and occupy some centres not previously reported to receive input. In the case of the ipsilateral isthmo-optic projection to the retina there was a substantial increase in the number of cells compared with normal chicks [O'Leary and Cowan: Devl. Brain Res. 12: 293-310, 1984]. A comparison of the extent of ipsilateral retinal afferents with that of normal chicks suggests that following loss of an eye two responses occur within the visual centres: in some centres there is a massive increase in the amount of ipsilateral terminals, whereas in others there is only a small increase. We propose that these responses are related to the intrinsic retinotopy within the visual centres. That is, highly retinotopic visual centres do not normally contain ipsilateral fibres, but following eye removal fibres from the ipsilateral eye are able to substantially innervate these regions. Presumably this effect is due to loss of the overriding influence of contralateral input, which would normally recognize and eliminate inappropriate ipsilateral fibres. In poorly retinotopic regions ipsilateral fibres are able to persist in both normal and monophthalmic chicks, as recognition cues may not be as precise as in highly retinotopic regions. Thus, the greater the retinotopic precision the finer the cues able to recognize ipsilateral fibres. PMID- 3113659 TI - Molecular differentiation of neurons from ependyma-derived cells in tissue cultures of regenerating teleost spinal cord. AB - Cells cultured from the caudalmost area of regenerating teleost spinal cord differ both morphologically and in terms of molecular architecture from those of more rostral (more fully differentiated) areas of the cord. The caudalmost regenerating cord consists of an ependymal tube. Cells from this region have flattened or partially flattened cell somas and short spike projections in vitro; they do not exhibit the rounded cell somas nor the long, thin, branching neurites typical of differentiated neurons. A series of cultures taken from different areas along the length of regenerating spinal cord were examined for molecular differentiation by staining with a monoclonal antibody against non-phosphorylated neurofilament protein (SMI 32). None of the cells from the caudalmost culture of the regenerating spinal cord stained with antibody SMI 32. In cultures of more rostral regenerated cord, the cells with neuronal morphology do stain positively with the anti-neurofilament antibody. This result suggests that the cells in the cultures of caudalmost cord represent relatively undifferentiated ependymal cells, or ependyma-derived cells, which later differentiate into neurons and glia in the regenerating spinal cord. PMID- 3113660 TI - In vitro assembly and isolation of neurofilaments and microtubules from mammalian CNS. AB - Neurofilaments were assembled in vitro from the high speed supernatant of mammalian CNS homogenate in a disassembly buffer containing 4-morpholine-ethane sulfonic acid, MgCl2 and EGTA at 4 degrees C in the presence of 4 M glycerol. The assembled neurofilaments were depolymerized by dialysis against the disassembly buffer and repolymerized by the addition of glycerol to the clarified supernatant obtained afer disassembly. The filament assembly reaction was complete in less than 30 s as measured by turbidimetric changes at 415 nm and did not require any added nucleotide. No assembly of filaments was detected when using frozen tissue. The assembled filaments corresponded to the enrichment of neurofilament triplet, the 210,000, 160,000 and 70,000 dalton polypeptides on SDS-polyacrylamide gels and appeared morphologically and immunochemically identical to neurofilaments isolated by axonal flotation methods. These studies demonstrate in vitro assembly of neurofilaments under native conditions which raises the possibility that like microtubules, neurofilaments or a subpopulation of neurofilaments might be in a dynamic state of assembly--disassembly in situ. PMID- 3113661 TI - Monoclonal antibodies to hydroxyindole O-methyltransferase from bovine pineal gland. AB - Hybridomas that produce monoclonal antibodies to bovine hydroxyindole O methyltransferase have been established by immunizing a mouse with hydroxyindole O-methyltransferase partially purified from bovine pineal glands followed by fusion of the spleen cells with myeloma NS-1 cells. Twenty-three clones have been isolated by screening the medium by two different methods. These clones produced various antibodies with different binding properties. Most of the antibodies belonged to IgG1 subtype, while 7 clones produced IgG2 alpha or IgG2 beta antibodies. Three antibodies inhibited enzymatic activity, whereas others did not. Antibodies of 7 clones recognized enzyme protein denatured with sodium dodecyl sulfate, while other antibodies reacted only with native enzyme protein. Thus a variety of monoclonal antibodies will offer us a good tool for immunohistochemical localization of the enzyme, immunoaffinity purification of hydroxyindole O-methyltransferase, and isolation of the cDNA clones encoding it. We also report here on the immunohistochemical demonstration of hydroxyindole O methyltransferase in bovine pineal gland and a new immunoaffinity procedure to purify the enzyme to homogeneity by use of monoclonal antibodies. PMID- 3113662 TI - Adrenal medulla grafts produce blood-brain barrier dysfunction. AB - The results of this study show that grafts of adrenal medulla into the rat brain parenchyma or ventricle produced significant blood-brain barrier dysfunction. Systemically administered protein rapidly entered either the grafts, the surrounding brain tissue or the cerebrospinal fluid. The grafted chromaffin cells avidly took up blood-borne radiolabelled amine. Thus, autonomic tissue transplants prevented normal reconstruction of the blood-brain barrier after surgery and indefinitely exposed host brain tissue to blood-borne compounds. PMID- 3113663 TI - Effects of intracarotid hyperosmolar mannitol in triethyl tin (TET)-induced rat brain edema--preservation of blood-brain barrier (BBB) in TET edema. AB - The effect of intracarotid hyperosmolar mannitol on the blood-brain barrier (BBB) in triethyl tin (TET)-induced rat brain edema was examined by using intravenous Evans blue (EB, MW 68,000) and Adriamycin (ADM, MW 580) as tracers. Three ml of 1.4 M mannitol solution were administered through the right carotid artery during 45 s for BBB opening. The barrier was opened for 60-120 minutes and then re established. The reversibility was preserved in TET-treated rats and controls. In fact, the intravenous injection of EB stained both TET-treated and non-treated cerebral hemispheres with mannitol-induced transient BBB disruption, but not without BBB disruption. BBB was resistant to both high and low molecular weight substances in TET-induced edema. The importance of this hyperosmotic studies provides the evidence for normal BBB function in TET-induced brain edema. PMID- 3113664 TI - Veratridine-induced activation of choline-O-acetyltransferase activity in rat hippocampal tissue: relationship to the veratridine-induced release of acetylcholine. AB - The effect of veratridine depolarization on the activity of 3 choline-O acetyltransferase (ChAT) fractions in rat hippocampal tissue was investigated. Those concentrations of veratridine which augmented acetylcholine (ACh) release also increased the activity of water and detergent soluble ChAT fractions. These results may suggest that the depolarization induced release of ACh is linked to an activation of ChAT activity. PMID- 3113665 TI - Dopamine-rich grafts ameliorate whole body motor asymmetry and sensory neglect but not independent limb use in rats with 6-hydroxydopamine lesions. AB - The capacity of dopamine (DA)-rich embryonic grafts to influence performance in a skilled motor task has been assessed. In two separate experiments, unilateral 6 hydroxydopamine lesions of forebrain DA systems induced a neglect of the contralateral limb and an almost total preference for use of the ipsilateral limb when reaching through the bars of a cage for food pellets. If the food paw was restrained, either by a bracelet or by injection of a local anaesthetic, the lesioned rats would continue to make many reaching attempts with the contralateral paw, but on the great majority of these attempts they were unsuccessful in grasping or retrieving food. DA-rich grafts, reinnervating the denervated caudate-putamen, provided no detectable benefit to the lesioned rats, neither in reducing the ipsilateral bias in their side preference, nor in increasing their success when constrained to reaching with the contralateral limb. This failure to benefit from the grafts is not due to the grafts themselves not being viable, since the same rats showed substantial compensation of whole body motor asymmetries in spontaneous and drug-induced rotation, and a reduction of asymmetry in a battery of neurological tests of sensorimotor function. The results are discussed in terms of the degree of anatomical integration of the grafts into the host neural circuitry, and the neural organization necessary for the performance of different classes of behavior. PMID- 3113666 TI - Intracellular calcium concentration during pentylenetetrazol-induced bursting activity in snail neurons. AB - To clarify the role of intracellular free calcium in the provocation of bursting activity, the intracellular calcium concentration was measured using calcium sensitive microelectrodes during pentylenetetrazol (PTZ)-induced bursting activity in snail neurons. In the PTZ-sensitive neurons of the snail, Euhadra peliomphala, the intracellular calcium concentration was higher than that in the normal state during PTZ-induced bursting activity, but lower than that which induced the calcium-activated potassium conductance elevation. By application of 50 microM calcium ionophore, A23187, a slight increase in intracellular calcium concentration with a slight depolarization occurred. Then a greater increase of intracellular calcium concentration with bursting activity was observed. By application of 100 microM A23187, a rapid and intense increase of intracellular calcium concentration with hyperpolarization was observed. These findings suggest that, for the provocation of bursting activity, sustained elevation of the intracellular calcium concentration, higher than that in the normal state but lower than that which evokes calcium-activated potassium conductance elevation, is required. PMID- 3113668 TI - Immunocytochemical analysis of proenkephalin-derived peptides in the amphibian hypothalamus and optic tectum. AB - [Met5]-Enkephalin-, [Met5]-enkephalin-Arg6-, [Met5]-enkephalin-Arg6-Phe7-, metorphamide- and BAM 22P-like peptides could be localized in the amphibian brain by immunocytochemistry. However, a [Met5]-enkephalin-Arg6-Gly7-Leu8-like peptide could not be detected in the brain of any anuran species with an antiserum that was capable of detecting this octapeptide in mammalian brain. A synenkephalin like peptide also could not be detected in the anuran brain with an antiserum that was capable of detecting the antigen in bovine and porcine brain. Although the intensity of proenkephalin-like immunoreactivity depended on the antiserum used, its distribution appeared to be identical with all of the effective antisera. Antisera directed against somatostatin and corticotropin-releasing factor stained perikarya, nerve fibers and terminals in the anuran brain with a distribution that was different from antisera directed against proenkephalin derived peptides. The distribution of proenkephalin-containing perikarya and nerve fibers in the regions of the anuran brain selected for study showed many similarities to the distribution of proenkephalin-containing perikarya and nerve fibers in the same regions of the amniote brain. PMID- 3113667 TI - Localized injections of 6-hydroxydopamine into lamina terminalis-associated structures: effects on experimentally induced drinking and pressor responses. AB - Electrolytic lesions of tissues surrounding the anteroventral third ventricle (AV3V) or injections of the chemical neurotoxin, 6-hydroxydopamine (6-OHDA) into the lateral cerebral ventricles result in virtually identical deficits in response to a variety of dipsogenic and pressor challenges. These observations have led to the hypothesis that the integrity of catecholamine (CA) projections into the AV3V region is a prerequisite for elicitation of these thirst and blood pressure responses. This hypothesis was tested in 6-OHDA-injected rats following protocols designed to deplete CA's in discrete structures associated with the lamina terminalis. Post-injection response deficits, coupled with histofluorescent assessments of CA depletions in specific anterior forebrain nuclei, support the stated hypothesis. In addition, the findings indicate that thirst deficits to systemic as well as central dipsogenic challenges are both selective and dissociable and that 6-OHDA lesions of any of the more ventrally situated target nuclei result in significantly attenuated blood pressure responses to centrally injected angiotensin II. PMID- 3113669 TI - The sensory projections of Drosophila mutants which show abnormal wing formation or flying behavior. AB - The central projection pattern of sensory neurones from the wing of Drosophila melanogaster arise from a small number of differentiated cell types which are localized in a precise and reproducible spatial pattern. We report here the distribution of the nerve pathways revealed by filling with peroxidase and the structure and number of the wing sensory receptors, in flies which have wings but which nevertheless are flightless, including one which presents abnormal wing formation. Our results indicate that in dumpy and taxi mutants, there are no detectable modifications in the neural projections or in the number and morphology of sensory receptors. Vestigial mutants however, present several alterations including the absence of the ovoid projection, a fact consistent with the existence of very few marginal bristles. The projection of the large companiform sensilla branch profusely along the ventromedial tract and more sensory fibers cross the midline in the mesothorax. Wings of vestigial mutants show a decrease in the number of large campaniform sensilla, and more importantly some receptors present abnormally oriented trichomes in the neighboring cells. PMID- 3113670 TI - A monoclonal antibody to non-phosphorylated neurofilament protein marks the vulnerable cortical neurons in Alzheimer's disease. AB - Various cytoskeletal proteins have been implicated in the formation of neurofibrillary tangles in Alzheimer's disease. A monoclonal antibody to non phosphorylated neurofilament protein labels a distinct subset of pyramidal cells in the normal human cortex which have a distribution very similar to that of neurofibrillary tangles in brains from patients with Alzheimer's disease. In addition, regions and layers that normally contain a high density of such cells, in Alzheimer's disease, have large numbers of neurofibrillary tangles and few remaining immunoreactive cells. PMID- 3113671 TI - High-frequency and medium-frequency components of different inspiratory nerve discharges and their modification by various inputs. AB - In decerebrate paralyzed cats, spectral analysis was performed on simultaneous recordings of efferent inspiratory nerves (phrenic, recurrent laryngeal, hypoglossal). Spectral peaks were present both in the high-frequency (HFO) range (50-100 Hz) and the medium-frequency (MFO) range (20-50 Hz). Different activities were coherent only in the HFO range, indicating that the HFOs arise in a common inspiratory pattern generator that drives the different motoneuron populations, whereas the MFOs are specific to different systems. PMID- 3113672 TI - Modification of opioid agonist binding by pertussis toxin. AB - Membrane fractions prepared from rat striate, cortex and midbrain were treated with pertussis toxin, which has been shown to adenosine diphosphate (ADP) ribosylate the GTP-binding protein Gi, reducing its coupling with receptors. In striatal membranes, treatment with 40 micrograms toxin per mg membrane protein labeled 60% of the Gi present and 70% of another G protein, Go; this treatments reduced binding of the opioid agonist [3H]D-Ala2-D-Leu5-enkephalin ([3H]DADLE) 20 50%, with the decrease largely reflecting a decreased affinity. In cortex, toxin treatment reduced [3H]DADLE binding by 35-70%, corresponding to ADP-ribosylation of 50% of Gi and 40% of Go. In midbrain, [3H]DADLE binding was unaffected by toxin treatment that ADP-ribosylated 86% of the Gi and 72% of the Go. These results provide further evidence that opioid receptors are associated with GTP binding proteins in striatum and cortex, where they have also been shown to inhibit adenylate cyclase. Despite the presence of Gi and Go in midbrain, however, there appears to be no coupling between them and opioid receptors. PMID- 3113673 TI - An immunocytochemical analysis of the ontogeny of the microtubule-associated proteins MAP-2 and Tau in the nervous system of the rat. AB - The developmental distribution patterns of beta-tubulin and the microtubule associated proteins, MAP-2 and Tau, were studied by immunocytochemistry with monoclonal antibodies. The analysis of the in situ distribution of these proteins in embryonic brain tissue revealed intense immunoreactivity for beta-tubulin in proliferative and migrating neuroblasts. On the contrary, no immunoreactivity for MAP-2 or Tau was detected in this neuroepithelium; specific immunostaining for these MAPs was only present in those neuroblasts which have reached their final destination within a developing brain area, and have initiated terminal differentiation, i.e. the sprouting of axons and dendrites. During the initial stages of neuritic outgrowth both MAPs were detected in the somatodendritic compartment of developing brain neurons; Tau was also present in axons. While the distribution of MAP-2 remained essentially the same throughout development, Tau was progressively lost from cell bodies and dendrites. This pattern of compartmentation was observed in pyramidal neurons of the cerebral cortex and hippocampus, as well as in cells of other brain regions (e.g. thalamus, hypothalamus, cerebral amygdala and tectum). It was not detected in cerebellar Purkinje cells which compartmentalize Tau to axons from the outset of neuritic differentiation, and in neurons of the Gasser ganglion which transiently express MAP-2 in axons. The expression and distribution of these MAPs was also analyzed in embryonic cerebellar and hippocampal pyramidal neurons grown in culture. Both MAPs were found in these cells as soon as 6 h after plating; they were also present in all of the neurites, axons and dendrites, that these cells extend after development in vitro for several days. With subsequence development (more than 4 days in vitro) MAP-2 was lost from axons, while Tau remained homogeneously distributed in both types of neurites. Taken collectively, the present results indicate that the development of the compartmentalized distribution of MAP-2 and Tau follows a complex pattern which is specific for each of these MAPs, and which varies as a function of the neuron type and the conditions under which the cell develops. In addition, the complex variations in the distribution of both MAPs during in situ and in vitro development make it unlikely that these proteins have a role in determining the fate of a neurite as an axon or a dendrite. PMID- 3113674 TI - Synapsin I: a regulated synaptic vesicle organizing protein. AB - Synapsin is a protein initially discovered and characterized as a target for cyclic AMP and Ca/calmodulin-regulated protein kinases that is concentrated in nerve endings and is localized on the surface of small synaptic vesicles. Synapsin shares antigenic sites and some local regions of homology with erythrocyte protein 4.1, although these proteins in general are quite different in sequence. Protein 4.1 and synapsin share several local regions of homology with erythrocyte spectrin alpha subunit. Protein 4.1 and synapsin may be related to each other through a common relationship with spectrin. Synapsin binds to synaptic vesicles and membrane sites with a Kd of 0.01-0.02 microM and associates with a Kd of 0.5-4 microM to spectrin, microtubules and neurofilaments in in vitro assays. Synapsin interconnects synaptic vesicles to membranes, and this activity is inhibited by phosphorylation with Ca/calmodulin-dependent protein kinase. Synapsin may have a role in neurons as a structural protein capable of interconnecting small synaptic vesicles with a number of proteins, including spectrin, microtubules, neurofilaments, and membrane sites. A physiological function of synapsin could be as a vesicle-organizing protein that mediates calcium-regulated association of vesicles with cytoskeletal proteins during axonal transport and attaches vesicles to active zones in nerve endings. PMID- 3113675 TI - Amelin and synapsin I are 4.1 related spectrin binding proteins in brain. AB - How do synaptic vesicles move towards the presynaptic plasma membrane, fuse with that membrane, and release their contents during synaptic transmission? The answers to these questions at the molecular level are just beginning to be understood. Synapsin I is a neuron specific phosphoprotein that is associated with the cytoplasmic surface of synaptic vesicles. During synaptic transmission, the translocation of the synaptic vesicles to the presynaptic membrane of the neuron is thought to be mediated through changes in the phosphorylation state of synapsin I. It has been suggested that synapsin I is a spectrin binding protein related to the erythrocyte cytoskeletal protein 4.1, which binds to the terminal ends of the erythrocyte spectrin tetramer. The interaction of synapsin I (through brain spectrin) with the neuronal cytoskeleton may be essential for regulating the movement of synaptic vesicles towards the presynaptic plasma membrane. In addition, we have identified another protein in brain that is immunologically and structurally more closely related to erythrocyte 4.1 than is synapsin I. This protein, termed amelin, is localized in the cell body and dendrites of the neuron, whereas synapsin I is found exclusively in the synaptic terminals, suggesting that there is a family of erythrocyte 4.1 related proteins present in brain with distinct subcellular distribution and functions. PMID- 3113676 TI - [Reconstitution of high-affinity galactose transport of Salmonella typhimurium in proteoliposomes: energization by lipoamide and NAD or by the membrane potential; inhibition by ATP]. AB - The binding protein-dependent galactose transport of Salmonella typhimurium has been reconstituted in proteoliposomes made from a partially purified protein fraction (containing the three membrane protein implicated in this transport and a lipoamide dehydrogenase activity) and soybean phospholipids. The reconstitution of galactose transport requires the addition of the purified galactose binding protein. Transport is energized either by reduced lipoamide and NAD or by the membrane potential and is inhibited by ATP. PMID- 3113677 TI - [Evolution of the retinal distribution of amacrine cells immunoreactive to phenylethanolamine-N-methyltransferase during postnatal development in the white rat]. AB - The phenylethanolamine-N-methyltransferase immunoreactive cells were demonstrated by the first postnatal day in whole-mounted retinas. They were distributed all over the retina in young rats (more numerous in the superior temporal quadrant) and were restricted to the superior retina in adult rats. PMID- 3113678 TI - [Ultrastructural labeling of the chromatoid body and the centriole-associated body using the DNase-gold colloidal complex in monkey spermatids]. AB - In Monkey spermatids at different steps of spermiogenesis, the use of DNase-gold complex showed, at the ultrastructural level, a labeling over the chromatin and concomitantly over the chromatoid body, centriole associated body and annular chromatoid body. The results obtained with the DNase-gold complex containing either DNA or actin led to discuss the nature of the substances revealed by the labeling in the cytoplasmic structures. PMID- 3113679 TI - [Unit activity of neurons of the posterior ventral nucleus of the thalamus for various waking stages in the normal cat]. AB - Using the electrocortical activity in the sensorimotor cortex as an index, three distinct levels of motionless waking can be identified in the cat, all three different from active waking and from slow sleep (attentive waking, quiet waking and drowsiness). It has now been shown that spontaneous and evoked single unit activities in n. ventralis posterior of the thalamus undergo significant changes when passing from one level of waking into another one. PMID- 3113680 TI - [Auditory competence of the newborn infant with regard to specific and non specific rhythms]. AB - This study is based on the analysis of modifications in the heart-rate of newborn infants (n = 12) hearing heartbeats at 72 and 120 bpm and metronome beats at 45, 72 and 120 bpm. The results show a selective discrimination of these acoustic stimulations by the infant. PMID- 3113681 TI - [Fetal perception and discrimination of speech stimuli; demonstration by cardiac reactivity; preliminary results]. AB - Human fetuses (35-38 ws GA), exposed to a repeated pair of syllables, either [ba] [bi] or [bi] [ba], at 95 dB SPL when in a low heart rate variability state, display a significant heart rate deceleration. Changing the order of the syllables in the pair, [ba] [bi] becoming [bi] [ba] (or the reverse), induces a new cardiac deceleration. This suggests that fetuses demonstrate auditory discrimination abilities for speech units like syllables. PMID- 3113682 TI - [Lack of transformation of the collagen substratum in collagen lattice cultures]. AB - Human dermal fibroblasts were seeded into collagen lattices (tridimensional meshwork) of two preparations: (1) acid-extracted, (2) pepsin-digested-calf skin collagens. Lattices prepared with pepsin-digested collagen retracted faster during the first 2 days, then the two preparations gave the same contraction pattern. Lattices of both preparations were contracted for up to 23 days and their collagens submitted to CNBr treatment. The patterns of CB-peptides were found identical for all the incubation periods tested. There is no formation of cross-links during the contraction process. PMID- 3113683 TI - [Extemporaneous analysis of myocardial performance by a programmable automatic dynamometer]. AB - This article describes a biophysical investigation to determine the physiological integrity of isolated cardiac fibers obtained during surgery. Immediate biopsy of myocardium can be analysed dynamically in various physiological conditions using an intelligent dynamometer controlled by an "APPLE II" microcomputer generally in less than fifteen minutes. Multiple tests including pharmacological and electrical properties of fibers can now be done with this cardiac analyser. Primary investigations on heart diseases show the importance of the method for evaluation of heart necrosis. PMID- 3113684 TI - [In vivo inhibition by ethyloxanilates of alkaline phosphatases of the cestode Echinococcus multilocularis]. AB - Alkaline phosphatases (E.C.3.1.3.1), membranous enzymes of the cestode Echinococcus multilocularis have been studied in the parasite and in the experimental host liver. Synthetic inhibitors interaction with metacestode alkaline phosphatases is reported. In regard to the alkaline phosphatases inhibition, the ethyloxanilate 2 is more efficient in the cestode itself than in the host liver. PMID- 3113685 TI - [Use of latex balls labelled by lectins in the demonstration of Salmonella Schistosoma mansoni receptor sites]. AB - Surface tegumental membrane of adult stage Schistosoma mansoni were examined using the latex sphere coated with Concanavalin A (Con A). Wheat germ agglutinin (WGA) and Protein A (PA). Competitive saccharide inhibitors glucose, mannose and methyl alpha-D-glucopyranoside were used for Con A. PMID- 3113686 TI - [Cell nucleus intervention in aluminium concentration by the rat liver cells. Experimental study]. AB - Intravenous injections of Al gluconate enhances immediately the aluminium content of the Rat liver. The cell nuclei are mainly involved in Al accumulation which still remains 10 min. After injection. This experimental model of Al overload is of great potential interest to study Al-nucleic acid interactions. PMID- 3113687 TI - [Quantitative variations during the intermoult cycle of peptides related to human growth hormone in Palaemon serratus (Crustacea; Decapoda)]. AB - Growth hormone-like peptides cross-reacting with an antiserum human specific were detected in the haemolymph, the midgut gland and stomach extracts of the prawn Palaemon serratus using radioimmunoassay. Parallelism was observed between the dilution sample curves and the hGH standard curve. Moreover, at least one peptide exhibiting a similar apparent molecular weight (22,000 daltons) with hGH was detected. In the three samples different amounts were detected during intermolt cycle: between 1.3 and 2.2 ng/ml in the haemolymph, 23 and 84 ng/g wet weight for the midgut gland, 12 and 71 ng/g ww for the stomach. The stages with highest values were respectively: D 1" and D 1"', D 1"' and D 2, D 3 and AB. PMID- 3113688 TI - [Possible role of the neuronal environment in the vascularization of an intracerebral graft]. AB - Fetal thalamic cells implanted into the excitotoxically lesioned thalamus of adult rats construct a neo-nucleus. This study shows that the vascular network of this neo-nucleus exhibits normal characteristics considering both the morphology (at the light and ultrastructural levels) and the presence of a blood-brain barrier for macromolecules. A role of the neuronal environment in this reconstruction is suggested. PMID- 3113689 TI - [Demonstration of synergy between the factor stimulating granulocytes and macrophages colonies and interleukin-I for the stimulation of prostaglandin E2 synthesis by bone marrow cells]. AB - Conditioned medium from P388 D1 cell line containing interleukin 1 (IL-1) and granulocyte macrophage colony stimulating factor (GM-CSF) can stimulate prostaglandin E2 (PGE2) production by murine bone marrow cells. In this work, we show that although GM-CSF (either purified from P388 D1 CM or murine recombinant GM-CSF) does not significantly alter bone marrow cell PGE2 production, its presence in P388 D1 CM is however necessary to induce this effect since the presence of anti GM-CSF antiserum completely abrogated the increase in PGE2 production in response to P388 D1 CM. In addition IL-1 tested alone does not not modify PGE2 release by bone marrow cells. However, the simultaneous addition of IL-1 and GM-CSF markedly increases PGE2 production. Thus, the ability of P388 D1 CM to stimulate PGE2 synthesis by bone marrow cells appears to result from a synergistic action between GM-CSF and IL-1. PMID- 3113690 TI - [Augmentation, by naloxone, of the frequency and amplitude of LH-RH pulses in hypothalamo-hypophyseal portal blood in the castrated ram]. AB - The effect of naloxone administration on the LH-RH secretion in hypophyseal portal blood and LH secretion in peripheral blood was studied in four short term castrated rams (between 2 to 4 days after castration). For two animals (A and B) given a single naloxone injection, an increase of LH-RH pulse amplitude was observed (A, 22.3 to 80.5 pg/ml and B, 22.5 to 34.5 pg/ml) with only a small (nonsignificant) increase in LH-RH pulse frequency. For animals C and D given four injections of naloxone, both LH-RH pulse amplitudes and LH-RH pulse frequency were increased. Means of LH-RH pulse amplitude increase from 29.3 to 65.1 pg/ml and from 34.6 to 50.8 pg/ml for animals C and D respectively and the number of LH-RH pulses detected during the 3 hrs. before and after the first injection of naloxone were respectively 3 vs. 5 and 3 vs. 7. Whereas all LH pulses were preceded with a LH-RH pulse in animals A and B, after the multiple naloxone injections in animals C and D, a rapid LH-RH pulse frequency was associated with a sustained increment of LH secretion in peripheral blood in such a way that individual LH pulses were not clearly defined. The present report is the first documentation on naloxone increasing the release of LH-RH secretion in hypophyseal portal blood of conscious, unrestrained, short-term castrated rams. The results indicate: (1) that the opiate antagonist naloxone is able to increase both the amplitude and the frequency of LH-RH discharge by the hypothalamus and (2), when the LH-RH pulse frequency exceeds one pulse every 30 min., discrete LH secretory episodes are not observed in peripheral blood. PMID- 3113691 TI - [In vitro release of hypothalamic corticoliberine in the rat: incubation of slices from the whole hypothalamus]. AB - An experimental system allowing both the incubation and rapid transfert of rat hypothalamic slices has been developed in order to approach the regulation of CRF secretion. The release of CRF has been quantified by a specific radioimmunoassay. Under basal conditions, immunoreactive CRF release reached an optimum of 96.2 +/- 10.4 pg/3 hypothalami/20 min. A depolarizing concentration of KCl (56 mM) or veratridine (50 microM) applied for 20 min. induced a 222 and 257% increase, respectively, in CRF release. The in vitro CRF values released under basal and stimulated conditions are comparable to those of other hypothalamic neuropeptides. Furthermore, in vitro CRF release from the hypothalamus is in the same order of magnitude as in vivo CRF secretion estimated by hypophysial portal blood collection or median eminence push-pull cannulation. PMID- 3113692 TI - [Modification of the strategy of intentional movement after lesions of the substantia nigra in the cat]. AB - Bilateral lesions of the substantia nigra were carried out in cats previously overtrained at performing a visually guided forepaw movement towards a moving target. Both their reaction time (RT) and movement time (MT) were impaired postoperatively. On the other hand, their pointing precision was unimpaired after lesion and even improved relative to the preoperative level. This improved accuracy persisted even when the duration of the movement had returned to normal. It is suggested that lesioned animals develop and keep a new strategy using visual feed-back throughout the movement, while normal cats, even on such a complex pointing task, mainly use visual information to trigger their movement. PMID- 3113694 TI - Cancer statistics. 1986. PMID- 3113693 TI - [Midazolam-alfentanyl anesthesia for retrograde catheterization of bile and pancreatic ducts]. PMID- 3113695 TI - Equine protozoal myeloencephalitis. AB - Equine protozoal myeloencephalitis (EPM) is a disease that produces neurologic signs of brain or spinal cord dysfunction. The causative organism is believed to be a Sarcocystis species of protozoa. A definitive diagnosis can only be made on histopathology of affected spinal cord or brain. No preventive measures or documented treatment is available at this time for suspected cases of EPM. PMID- 3113696 TI - Medical management of spinal cord disease. AB - In spinal cord disease of horses, a complete history, neurologic examination, and adjunctive diagnostic procedures are very helpful in establishing a tentative diagnosis; however, a definitive diagnosis may be difficult or impossible to establish antemortem. Medical management should be initiated with full consideration of possible etiologies and knowledge of the effects and consequences of medical therapies. This article discusses the drugs commonly used in the management of spinal cord disease and the rationale for their use. PMID- 3113697 TI - The bone lining cell: a distinct phenotype? AB - It is argued that the flat cells that line nonremodeling endosteal bone surfaces are a distinct phenotype. These cells have a distinct morphology and they most likely have important functional roles in skeletal physiology, metabolism, and remodeling. For these reasons this cell seems deserving of a proper name. The name bone lining cell seems to have gained some acceptance but there will be continued confusion as long as skeletologists use this same term to generically describe cells that line bone surfaces, regardless of their actual identity. PMID- 3113698 TI - Compositional analysis of collagen from patients with diverse forms of osteogenesis imperfecta. AB - Collagen was extracted by pepsin treatment from various tissues and skin fibroblasts of 23 patients belonging to different types of osteogenesis imperfecta (OI), and characterized by molecular sieve and ion exchange chromatography, gel electrophoresis, and amino acid analysis. We found an elevated collagen III/I ratio in the skin of one patient with OI type I but almost normal values in skin fibroblasts of two other patients of this OI type. Five patients with OI type II had a normal collagen III/I ratio in their skin and skin fibroblasts, but the degree of hydroxylation of lysine residues in collagen I and III from their skin, bone, calvarium, and noncalcified calvarial tissue was increased. Patients belonging to OI types II, III, and IV had also considerable amounts of collagen III in their long bones, while bone tissue from controls contained only type I collagen. The content of type V in calcified tissues was virtually the same in controls and patients. PMID- 3113699 TI - Biological characterization of interleukin-1-like cytokine produced by cultured bone cells from newborn mouse calvaria. AB - We have investigated the role of interleukin-1 (IL-1) and IL-1-like factor in the regulatory mechanisms of a bone remodeling system. To determine whether the bone cell itself produces IL-1-like cytokine, we examined bone cells cultured from newborn mouse calvaria. Bone cells migrating from fragments of newborn mouse calvaria were used in this study. We also used bone cells obtained by consecutive digestion of the calvaria with enzymes. These bone cells were cultured in fetal calf serum-containing alpha-MEM. IL-1-like cytokine activity was measured by incorporation of [3H]thymidine into C3H/HeJ thymocytes stimulated with PHA. When treated with lipopolysaccharide (LPS) from Escherichia coli 0111 B4, the cultured bone cells produced a significant amount of IL-1-like cytokine. The maximum concentration of IL-1-like cytokine was observed in culture supernatants of the bone cells cultured for 24 hours with the LPS in serum-free medium. The IL-1-like cytokine closely resembles IL-1 in some of its biological characteristics: stimulation of mitogen-induced thymocyte proliferation, stimulation of fibroblast proliferation, pyrogenicity, and molecular weight. These results show that cultured bone cells from newborn mouse calvariae produce an IL-1-like cytokine that closely resembles IL-1. PMID- 3113700 TI - Developing antler, a model for endocrine regulation of bone growth. Concentration gradient of T3, T4, and alkaline phosphatase in the antler, jugular, and the saphenous veins. AB - Thyroxine (T4), triiodothyronine (T3), and alkaline phosphatase (AP) were assayed monthly in white-tailed deer plasma obtained from the antler (A), jugular (J), and the saphenous (S) veins during the period of antler growth and the period of mineralization. The concentrations of T3, T4, and AP in the J and S were not significantly different in any month. During the most intense antler growth period (June and July) AP levels were significantly higher and T3 significantly lower in A as compared to J and S, but no differences were found during the mineralization phase in August. T3 values from all three veins were significantly lower in the mineralization period than J and S values during the growing phase. Variations of T4 levels between A, J, and S as well as differences between months were only negligible. The data indicate that AP is produced in large quantity in the antler tissue during the growth period, but the amount is sharply reduced during the mineralization phase. T3 is utilized in the growing antler; the rate of utilization correlates with the intensity of antler growth. T4 is probably not utilized in the antler bone. Developing antler might be used as a model to study growth and mineralization processes of bony tissues. PMID- 3113701 TI - Effects of dentin phosphophoryn on precipitation of calcium phosphate in gel in vitro. AB - In vitro precipitation of calcium phosphate was carried out using a one dimensional double diffusion system in agar gel. Bovine dentin phosphophoryn enhanced the sharpness of the precipitation bands, although it reduced the total amount of the precipitates. Dephosphorylated phosphophoryn had no effect on the pattern of precipitates. Therefore, phosphophoryn is thought to raise the local density of nucleation in spite of its inhibitory activity on apatite formation. PMID- 3113702 TI - Loss of proteoglycans during decalcification of fresh metaphyses with disodium ethylenediaminetetraacetate (EDTA). AB - Recent immunofluorescent and histochemical data did not detect changes in the concentration of proteoglycans between noncalcified and calcified cartilage in fetal bovine growth plate or metaphyseal bone. These findings were constant, regardless of prior fixation before demineralization with disodium ethylenediaminetetraacetate (EDTA) or prior demineralization before fixation. Previous experience has shown that EDTA can extract proteoglycans from calcified cartilage. With this in mind, we determined the amount of proteoglycan extracted from calcified cartilage in metaphyseal bone and uncalcified growth plate cartilages during decalcification of unfixed fresh tissues with EDTA. To this end, fresh growth plate cartilages and metaphyses were decalcified at 5 degrees C for 48 hours in a buffered solution of EDTA to which several protease inhibitors were added. Under these conditions 20-25% of the total proteoglycan (measured as uronic acid and hexosamine) was extracted from mineralized cartilage but only about 1% from the uncalcified (growth plate) cartilages. Thus, histochemical and immunohistochemical studies appear to be insensitive measures of proteoglycan concentrations in histological sections of mineralized tissue and may not give quantitative information. PMID- 3113704 TI - Measurement of potassium turnover in rod photoreceptors in toad isolated retina using ion-selective microelectrodes. AB - Ion-selective microelectrodes (ISMs) were used to measure the turnover of intracellular K+ (Ki+) in rods in the isolated retina of the toad, Bufo marinus. The light-evoked hyperpolarization of rods decreases their passive K+ efflux, which in combination with active K+ uptake, decreases extracellular K+ concentration, Ko+.Rb+ substitutes for K+ in these processes. The turnover of Ki+ was measured as Rb+ and K+ were exchanged, using ISMs that were approximately five times more sensitive to Rb+ than to K+. When Ko+ was replaced by Rbo+, the light-evoked decrease in K+ efflux produced only a small change in ISM voltage, delta VISM, owing to the background of Rbo+. As Rbi+ replaced Ki+, the efflux shifted from K+ to Rb+ and delta VISM grew in amplitude. After loading the rods with Rbi+, Rbo+ was replaced by Ko+. The light-evoked decrease in Rb+ efflux lead transiently to a large delta VISM, since the change in Rbo+ was superimposed upon a background of Ko+. As Ki+ replaced Rbi+, the amplitude of delta VISM declined. When measured using this technique, the turnover of Ki+ was 95% complete in approximately 15 min. In low Ca2+ solutions, transmembrane fluxes of K+ (Rb+) increased and turnover of Ki+ occurred more rapidly. During background illumination, transmembrane fluxes of K+ (Rb+) decreased and turnover of Ki+ was slowed. These experiments have provided independent corroboration of earlier observations concerning rod K+ fluxes. This ISM-based technique also may be useful in measuring K+ turnover in other cell types. PMID- 3113703 TI - Effects of nandrolone decanoate on forearm mineral density and calcium metabolism in osteoporotic postmenopausal women. AB - Although anabolic steroids have been used for many years to treat osteoporosis there is little available evidence about their efficacy or mode of action. These agents have recently been shown to produce an increase in total body calcium and bone density and it has been suggested that they stimulate bone formation. In this study 27 osteoporotic postmenopausal women were given 50 mg of nandrolone decanoate intramuscularly, every 2 or 3 weeks for 3 months, and the changes in forearm mineral density, fasting plasma, and urinary calcium, urinary hydroxyproline, and radiocalcium absorption were measured. Associated with a rise in forearm mineral density was a significant fall in fasting urinary calcium, but no significant change in fasting urinary hydroxyproline. The plasma calcium and phosphate fell significantly and there was a significant rise in the renal tubular reabsorption of calcium and a fall in the renal tubular reabsorption of phosphate. In a subset of 22 patients there was a significant rise in radiocalcium absorption. The results are consistent with the concept that nandrolone exerts a significant positive effect on bone formation and that this results in a fall in the fasting plasma calcium level, and consequently calcium excretion. PMID- 3113705 TI - Pathophysiology of pH and Ca2+ in bloodstream and brain. AB - The highlights of the literature and our work on tetany and hyperventilation are reviewed. Our studies concern the following: (1) the changes of [Ca2+] in circulating plasma caused by respiratory and "metabolic" acidosis and alkalosis; (2) critical plasma [Ca2+] levels associated with signs of tetany and neuromuscular blockade; (3) changes in cerebral [Ca2+]o caused by hypo- and hyper calcaemia, and the changes in cerebral [Ca2+]o and pHo caused by acute systemic acidosis and alkalosis; and (4) effects of changing [Ca2+]o and pHo levels on synaptic transmission in hippocampal formation. Our main conclusions are (1) changes of plasma [Ca2+] caused by "metabolic" pH changes are greater than those associated with varying CO2 concentration; (2) acute systemic [Ca2+] changes are associated with small cerebral [Ca2+]o changes; (3) the decreases in systemic and cerebral [Ca2+]o caused by hyperventilation are too small to account for the signs and symptoms of hypocapnic tetany; (4) moderate decrease of [Ca2+]o depresses and its increase enhances synaptic transmission in hippocampal formation; and (5) H+ ions in extracellular fluid have a weak depressant effect on neuronal excitability. CO2 is a strong depressant, which is only partly explained by the acidity of its solution. CO2 concentration is a significant factor in controlling cerebral function. PMID- 3113706 TI - Intracellular free magnesium in excitable cells: its measurement and its biologic significance. AB - As a necessary cofactor for hundreds of enzymes, intracellular Mg2+ influences a wide range of cellular functions such as transmembrane transport of other ions, glycolysis, respiration, muscle contraction, and phosphorylation of ion channels. Unlike Ca2+, Mg2+ does not seem to have a "trigger" function. However, the wide range of enzymes requiring Mg2+ to be activated suggests that Mg2+ plays a pivotal role in fine control and coordination of cell activity, determining the "set point" of hundreds of metabolic reactions. In this sense, intracellular Mg2+ might be regarded as a static rather than a dynamic regulator of cell function. Little is known about the mechanisms by which excitable and other cells keep their [Mg2+]i within narrow limits against large electrochemical gradients. Furthermore, the actual basal level of [Mg2+]i has been the subject of recent controversy. In the present paper the roles of intracellular Mg2+ on cell function as well as four current techniques for measuring [Mg2+]i are briefly reviewed. These techniques are (i) metallochromic indicators, (ii) 31P nuclear magnetic resonance, (iii) null point for plasma membrane permeabilization using the ionophore A23187 and, (iv) Mg2+-selective microelectrodes. The relative advantages and disadvantages of each of these techniques are discussed with special emphasis on Mg2+-selective microelectrodes. PMID- 3113707 TI - Changes in the intracellular free calcium concentration of Aplysia and leech neurones measured with calcium-sensitive microelectrodes. AB - The intracellular free Ca concentration was measured in invertebrate neurones using single-barrelled and double-barrelled neutral-carrier microelectrodes. The electrodes were calibrated in solutions containing different Ca concentrations between 1 mM and 0.01 microM. The electrode responses were also tested at different ionic strengths and at varying Na concentrations. The electrodes responded with 25-30 mV per 10-fold change in Ca concentration between 1 mM and 1 microM and with 10-25 mV between 1 and 0.1 microM Ca. The intracellular free Ca concentration was measured to be between 0.1 and 0.7 microM in the neurones. The changes of intracellular Ca in identified voltage-clamped neurones of Aplysia californica were recorded during iontophoretic injections of Ca2+ or EGTA. The decrease of intracellular Ca following EGTA injection was correlated with the suppression of the Ca-dependent K current and with the reduction of Ca-induced inactivation of voltage-dependent Ca current. In identified neurones of the leech Hirudo medicinalis a reversible increase of intracellular Ca2+ was recorded after inhibition of the Na-K pump, either by addition of ouabain (0.5 mM) or by lowering the external K concentration (0.2 mM). This rise in intracellular Ca2+ did not occur, and was even reversed, in the absence of external Na, suggesting the existence of Na-Ca exchange across the leech neuronal membrane. PMID- 3113708 TI - The 1986 Upjohn award lecture. Interaction of chemicals with hemoproteins: implications for the mechanism of action of porphyrinogenic drugs and nitroglycerin. AB - The ferrochelatase inhibitory activity of a variety of analogues of 3,5 diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) was studied in chick embryo liver cells. The ferrochelatase inhibitory activity of the 4-butyl, 4 pentyl, and 4-hexyl analogues was considered to be due to catalytic activation by cytochrome P-450 leading to heme alkylation and formation of the corresponding N alkylporphyrins. The relative ferrochelatase inhibitory activity of the DDC analogues has implications for a postulated model of the binding of porphyrins in the ferrochelatase active site. 3-[2-(2,4,6-Trimethylphenyl)thioethyl]-4 methylsydnone (TTMS) was shown to be a potent porphyrinogenic agent and to inhibit ferrochelatase in chick embryo liver cells. A related sydnone, 3-benzyl-4 phenylsydnone did not inhibit ferrochelatase activity. These results supported the idea that the porphyrinogenicity of TTMS was due to catalytic activation by cytochrome P-450 leading to heme alkylation and formation of N vinylprotoporphyrin which inhibits ferrochelatase. Polychlorinated biphenyls, phenobarbital, nifedipine, and a large number of structurally different chemicals which are porphyrinogenic in chick embryo liver cells inhibit uroporphyrinogen decarboxylase by an unknown mechanism. Thus drug-induced porphyrin biosynthesis in chick embryo liver cell culture appears to be caused by inhibition of either ferrochelatase or uroporphyrinogen decarboxylase. The biotransformation of nitroglycerin by human red blood cells is due to a combination of a sulfhydryl dependent enzymatic process and an interaction with reduced hemoglobin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113710 TI - Expenditures on health care in British Columbia [correction]. PMID- 3113709 TI - A comparative study of glyceryl trinitrate biotransformation and glyceryl trinitrate induced relaxation in bovine pulmonary artery and vein. AB - Recent evidence supports the hypothesis that the mechanism by which glyceryl trinitrate induces relaxation of vascular smooth muscle involves the biotransformation of glyceryl trinitrate. This study was conducted to determine if there was a direct correlation between the capacity of vascular smooth muscle preparations to biotransform glyceryl trinitrate and their sensitivity to the relaxant effect of this organic nitrate. Isolated bovine pulmonary arteries and veins were contracted submaximally and cumulative dose-response relationships to glyceryl trinitrate were obtained; the vein was approximately 10 times more sensitive than the artery to glyceryl trinitrate induced relaxation. In a separate series of experiments, these vascular tissues were contracted submaximally and incubated with 0.5 microM [14C]glyceryl trinitrate for 2 min, during which glyceryl trinitrate induced relaxation was monitored. At 2 min, tissue samples were taken for determination of glyceryl trinitrate and glyceryl 1,2- and 1,3-dinitrate content by thin-layer chromatography and liquid scintillation spectrometry. Biotransformation of glyceryl trinitrate to glyceryl dinitrate occurred concomitantly with relaxation of these blood vessels. The concentration of glyceryl dinitrate in the vein was significantly less than that in the artery (p less than or equal to 0.05), even though significantly greater relaxation of the vein than the artery was observed (p less than or equal to 0.05). From these data, a simple linear relationship between glyceryl trinitrate biotransformation and relaxation is not apparent. PMID- 3113711 TI - Cutaneous Waldenstrom's macroglobulinemia. A report of a case successfully treated with radiotherapy. AB - Waldenstrom's macroglobulinemia is a lymphoproliferative disorder that only rarely exhibits specific cutaneous findings. The authors present a case of Waldenstrom's macroglobulinemia in which the patient developed cutaneous lesions while his systemic disease seemed to be under control with chlorambucil therapy. A review of the scant literature regarding the response of cutaneous Waldenstrom's to treatment suggests that the skin lesions do not respond well to systemic therapy. This case was successfully treated with radiotherapy. PMID- 3113713 TI - Acute gangrene of the scrotum and penis in four hematologic patients. The usefulness of hyperbaric oxygen therapy in one case. AB - We describe four cases of Fournier's gangrene complicating the postchemotherapy aplastic phase (polymorphonuclear cells [PMN] less than 500/microliter) in three patients with acute leukemia and one patient with non-Hodgkin's lymphoma. Blood and local cultures from two patients contained Pseudomonas aeruginosa, and local cultures from another patient grew both P. aeruginosa and Proteus rettgeri. Early recognition and aggressive antibiotic and surgical treatment with granulocyte recovery were fundamental factors in resolution of the gangrene in three of the four patients. Hyperbaric oxygen therapy, never reported in hematologic patients, was also very useful in one patient in whom the clinical course was particularly acute. PMID- 3113712 TI - A comparative study of dibromomannitol and busulfan in the treatment of chronic myeloid leukemia. A study of cancer and leukemia group B. AB - In a prospective, randomized trial the effectiveness of dibromomannitol (DBM), a brominated sugar alcohol derivative, was compared to busulfan in previously untreated patients. One hundred thirty-one patients were evaluated for response and survival. The effective dose of DBM was 4 mg/kg. The persistence of sensitivity to either DBM or busulfan was shown in a quantified fashion. Despite initial reports of the alleged unique effectiveness of DBM in treating chronic myeloid leukemia (CML), this study did not disclose any advantage of DBM over busulfan. Multivariate analysis investigating the importance of prognostic factors in CML indicated that age, sex, splenomegaly, and initial platelet count were important for predicting survival. Determination of such factors in CML are valuable in deciding those patients who could benefit from alternative forms of therapy. It also insures that study results are related to treatment rather than selection of patients with favorable or unfavorable prognostic factors. PMID- 3113714 TI - Intraoperative radiation therapy in patients with bladder cancer. A review of techniques allowing improved tumor doses and providing high cure rates without loss of bladder function. AB - Conventional external beam irradiation, using modern megavoltage techniques and doses that do not harm bladder function, will permanently eradicate local bladder cancer in 30% to 50% of patients, compared with 70% to 90% with cystectomy. In appropriately chosen patients, open surgery can safely provide excellent exposure for the selective delivery of more radiant energy directly to the tumor and less to the uninvolved portion of the bladder. Intraoperative radiation therapy, by either a removable radium or iridium implant or a large single dose of electrons, has been reported to be safe and can permanently cure the bladder of cancer and also preserve bladder function in more than 75% of patients with solitary tumors that invade into but not beyond the bladder muscle. With the increasing interest in and availability of intraoperative radiation therapy in the US, this curative and bladder-sparing treatment for operable patients with bladder cancer invading the trigone is appropriate for careful clinical trial. PMID- 3113715 TI - Stage C adenocarcinoma of the prostate. An analysis of 551 patients treated with external beam radiation. AB - We retrospectively reviewed records of 551 patients with clinical Stage C prostatic adenocarcinoma treated with 60 to 70 Gy external beam radiation. Elective pelvic node irradiation was given to 247 patients (45%). Follow-up for all surviving patients ranged from 16 to 201 months (median, 6.5 years; mean, 7 years). The 5-, 10-, and 15-year uncorrected actuarial survival rates were 72%, 47%, and 27%, respectively. Disease-free survival rates were 59%, 46%, and 40% at the corresponding times. Actuarial local control rates were 88%, 81%, and 75% at 5, 10, and 15 years, respectively. Disease-free survival was adversely affected by high pathologic grade, disease fixed to the pelvic sidewall, invasion of the bladder, prior transurethral resection, hydronephrosis, and elevated serum levels of prostatic acid phosphatase and creatinine. Elective pelvic node irradiation did not improve the outcome. Complications of treatment were acceptable: minor anorectal and/or urinary symptoms, 11%; mild to moderate complications, 19%; serious problems requiring surgery, 3%. It is concluded that localized, high energy external beam irradiation provides excellent local control of disease, low morbidity, and 5-, 10-, and 15-year survival rates that have not been rivaled by other treatment. PMID- 3113716 TI - The incidence of multifocal cerebral gliomas. A histologic study of large hemisphere sections. AB - A series of 241 gliomas (astrocytomas, oligodendrogliomas, glioblastomas, and subependymal giant-cell astrocytomas) was studied. This represents all the gliomas examined post mortem over 25 years at one hospital. Two hundred and one cases (85%) were apparently solitary tumors; of the 40 cases with multiple tumor foci, 23 (9.5%) were true multicentric gliomas. After excluding cases in which there was concomitant disease (neurofibromatosis, tuberose sclerosis, or multiple sclerosis), 18 cases of multicentric tumor (7.5%) remained. Multicentric tumors with different histologic appearances accounted for 2.9% of the series. Celloidin embedded whole brain sections proved invaluable for the detection of microscopic neoplastic foci and unsuspected diffuse spread. The estimated incidence of multiplicity in gliomas is higher than in most series, but the findings suggest that detection of multifocal neoplastic change in these tumors is directly related to the extent to which the brain is sampled, and that figures obtained in this study may well underestimate the true incidence. PMID- 3113717 TI - Small round blue cell sarcoma of bone mimicking atypical Ewing's sarcoma with neuroectodermal features. An analysis of five cases with immunohistochemical and electron microscopic support. AB - Ewing's sarcoma (ES) of bone may occasionally display rosette-like textures mimicking Homer-Wright ones, as seen in neuroectodermic neoplasms (neuroblastoma, peripheral neuroepithelioma). Of a group of 39 cases of ES, reviewed with electron microscopic study, the authors have isolated five atypical ES, which histologically also possessed neuroectodermic traces. These tumors were composed of small round blue cells with rosette-like figures and cytoplasmic glycogen. The immunohistochemical analysis showed positivity for neuron-specific enolase (NSE) as well as for HNK-1 (leu-7) monoclonal antibody. Electron microscopic examination confirmed the tumor cell as being of small round type, with a dense chromatine pattern and the presence of isolated dendritic processes, as well as synaptic-like buttons; intermediate filaments, neurotubuli, and dense-core neurosecretory granules also were seen. Moreover, in two cases basement-like condensations surrounded some cells. Scanning electron microscopic study in one case confirmed the presence of rosette-like figures and cell elongations with short dendritic projections of the cytoplasm. Clinically and radiologically these cases showed features similar to ES of bone; one case, located in the chest wall, had a local relapse after treatment, with the histologic features of a pleomorphic neuroblastoma. The authors conclude that these tumors resemble closely immature neuroepithelioma of soft tissue but, being primary to bone, are superimposable on those described as "neuroectodermal tumors of bone." PMID- 3113718 TI - DMBA induced DNA damage and repair in mammary epithelial cells in vitro measured by a nick translation assay. AB - A new E. coli DNA polymerase I directed nick translation assay was used for measuring 7,12-dimethylbenz[a]anthracene-induced in situ DNA damage and repair in mouse mammary epithelial cells in monolayer culture. The nick translation assay was capable of detecting a DMBA-dose dependent significant increase of DNA damage, and the same assay also allowed monitoring of the DNA repair activity provoked by DMBA treatment of the epithelial cells. This relatively simple method thus provides a rapid assay for carcinogen-induced in situ DNA damage and repair in an epithelial cell tumorigenic system. PMID- 3113719 TI - Chromosome marker and enhanced expression of c-Ha-ras in a DMBA-induced erythroleukemia cell line (D5A1). AB - Oncogene activation induced by chromosomal changes is now regarded as one of the most important phenomena during carcinogenesis. We have reported c-abl activation in a rat leukemia cell line K3D, caused by a secondary chromosomal translocation. Another erythroblastic leukemia cell line D5A1, originally derived from a leukemia induced by 7,12-dimethylbenz(a)anthracene (DMBA) in a Long-Evans rat, is characterized by a marker chromosome 1q+, which also probably occurred as a secondary change. In this cell line, the transcription level of Ha-ras related mRNA increased compared with other cell lines. By the in situ hybridization technique, the c-Ha-ras locus was assigned to 1q43 and the breakpoint 1q+. Because the breakpoint was so near the c-Ha-ras locus on the chromosome, the present system may provide a model of activation of the c-Ha-ras gene brought about by chromosomal translocation. PMID- 3113720 TI - Comparison of DNA interstrand cross-linking and strand breakage by 1,3-bis(2 chloroethyl)-1-nitrosourea in polyamine-depleted and control human adenocarcinoma cells. AB - Recent evidence from our laboratory and from others suggested that pretreatment with alpha-difluoromethylornithine (DFMO) sensitizes some human and rodent tumor cell lines to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Many human tumor cells are resistant to chloroethylnitrosourea-induced DNA interstrand cross-linking and cell kill due to their high levels of the DNA repair protein O6-alkylguanine DNA alkyltransferase. We therefore investigated DFMO-mediated sensitization to BCNU in BCNU-sensitive and -resistant cells. Colony formation assays were used to compare BCNU cytotoxicity in DFMO-pretreated and control cultures of two colon tumor lines, HT-29 cells, which have high alkyltransferase levels and thus are BCNU-resistant, and BE cells, which are deficient in this repair capacity and thus are BCNU-sensitive. Polyamine depletion significantly enhanced BCNU cytotoxicity only for the repair-proficient HT-29 cell line. BE cells were 40 fold more sensitive to BCNU than were HT-29 cultures. However, in BE cells, no effect of polyamine depletion was found on cellular response to BCNU treatment at 72 h after DFMO treatment. Reverse-phase high-performance liquid chromatography assays of polyamine concentrations in cell extracts verified that DFMO produced comparable degrees of polyamine depletion for both cell lines. DNA alkaline elution analysis was used to monitor BCNU-induced formation of DNA single strand breaks, DNA interstrand cross-links, and DNA-protein cross-links. Equal concentrations of BCNU produced similar levels of strand breaks and DNA-protein cross-links in DFMO-pretreated and control cultures for both cell lines. These data suggest that DNA in polyamine-deficient HT-29 and BE cells is not more accessible to BCNU than is DNA in controls. No DNA interstrand cross-links were detected in either DFMO-pretreated or control HT-29 cells after BCNU treatment. Further, in BE cells which accumulate BCNU-induced DNA interstrand cross-links, no increase in the measureable levels of cross-links resulted from polyamine deficiency. Our observations suggest that mechanisms other than increased DNA interstrand cross-link formation may be mediating the enhanced efficacy of BCNU in polyamine-deficient HT-29 cell cultures. Our findings may also imply that cellular targets for BCNU other than DNA damage may be responsible for DFMO induced chemosensitization in the repair-proficient cells. PMID- 3113721 TI - Combined chemoseparation and immunoseparation of clonogenic T lymphoma cells from human bone marrow using 2'-deoxycoformycin, deoxyadenosine, 3A1 monoclonal antibody, and complement. AB - Chemoseparation and immunoseparation techniques have been combined to eliminate malignant clonogenic T lymphoma cells from human bone marrow. Incubation with 5 microM 2'-deoxycoformycin and 500 microM deoxyadenosine has eliminated 2 logs of HSB-2 T lymphoma cells from a 20-fold excess of irradiated human bone marrow. Multiple incubations with 3A1 antibody and rabbit complement eliminated approximately 2 logs of HSB-2 cells from similar mixtures. Used in combination, the 2 techniques eliminated up to 4 logs of T lymphoma cells. Incubation of normal human bone marrow under similar conditions failed to affect growth of granulocyte-macrophage colony-forming cell units, burst-forming erythroid units, or multipotential erythroid-granulocyte-megakaryocyte-macrophage colony-forming hematopoietic progenitor cells units. PMID- 3113722 TI - Therapeutic potential of tumor necrosis factor-alpha and gamma-interferon in experimental human ovarian cancer. AB - We have studied the activity of recombinant human gamma-interferon and recombinant human tumor necrosis factor alpha against four human ovarian cancer i.p. xenografts OS, LA, HN, and DO derived from primary tumor material. In the OS xenograft all control mice died by 42 days and therapy starting 7 days after tumor cell injection with 5 X 10(4) units recombinant human gamma-interferon or 1 microgram recombinant human tumor necrosis factor alpha alone had no significant effect on cumulative survival in three separate experiments. However, a combination of the two agents resulted in 85% cumulative survival at 150 days. This combination therapy also significantly increased survival of mice treated as late as 21 days after tumor cell injection. In the LA xenograft (where control mice were all dead by 23 days) therapy with either agent alone, or a combination, more than doubled survival time of mice. In the HN xenograft all control mice were dead at 22 days whereas either therapy alone or in combination gave +85% cumulative survival at 100 days. In a fourth xenograft, DO, survival of mice in the combination therapy group was significantly increased. Thus these two biological therapies, alone or in combination, show significant activity against human ovarian cancer cells. PMID- 3113723 TI - Progressive growth of immunogenic tumors: relationship between susceptibility of ascites P815 tumor cells to T-cell-mediated lysis and immune destruction in vivo. AB - Progressive growth of the P815 mastocytoma as an ascites in either normal or immunodepressed, semisyngeneic B6D2F1 mice resulted in the outgrowth of tumor cells resistant to lysis in vitro by tumor-specific cytotoxic T-lymphocytes (CTLs). Additional testing in vitro showed that late ascites tumor cells also developed a progressive decline in susceptibility to lysis by alloreactive CTLs. The decline in susceptibility to lysis by alloreactive CTLs. The decline in susceptibility to lysis by tumor-specific CTLs was not the result of the loss of tumor-associated antigens, since late tumor cells had the capacity to inhibit the lysis of early, log-phase growth P815 cells in a cold-target inhibition assay. Further studies showed that later, CTL-resistant tumor cells regained susceptibility to CTL lysis if they were incubated for 24 h in vitro. Studies of susceptibility to in vivo immune mechanisms demonstrated that late tumor cells were as susceptible as early tumor cells to adoptive immunotherapy with spleen cells taken from mice immunized against the early tumors. Taken together, these studies suggest that the resistance of late tumor cells to in vitro lysis by CTLs is a reversible phenomenon that may have no relevance to the expression of antitumor immunity in vivo. PMID- 3113724 TI - Species specificity in the metabolism of N-nitrosobis(2-oxopropyl)amine and N nitroso(2-hydroxypropyl)(2-oxopropyl)amine to mutagens by isolated rat and hamster hepatocytes. AB - The metabolic activation of the carcinogens N-nitrosobis(2-oxopropyl)amine (BOP) and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) by Fischer rat and Syrian hamster hepatocytes was investigated in order to determine the existence of species differences in the induction of cell mutation. The conversion of BOP and HPOP into forms mutagenic to V79 cells was studied by using the hepatocyte mediated mutagenicity assay. Mutations at the hypoxanthine:guanine phosphoribosyltransferase locus and the Na-K-ATPase locus were scored by the induction of 6-thioguanine resistance (TGr) or ouabain resistance (Ouar), respectively. Hepatocytes of both species were capable of converting BOP and HPOP to mutagens for V79 cells in a dose-dependent manner. Metabolism of BOP by rat hepatocytes resulted in higher mutation frequencies than that by hamster hepatocytes. At a BOP concentration of 240 microM, rat hepatocyte metabolism yielded 90.7 TGr mutants and 19.5 Ouar mutants per 10(5) V79 cells. At the same concentration, hamster hepatocyte metabolism of BOP yielded 54.1 TGr mutants and 13.0 Ouar mutants per 10(5) V79 cells. These results did not correlate with the known carcinogenic potency of BOP in the hamster as compared to the rat. Hamster hepatocytes carried out the catabolism of BOP to CO2 at faster rates than rat hepatocytes; therefore, the species difference in mutagenic activation was not due to a defect in BOP uptake or metabolism by hamster hepatocytes. In contrast, metabolism of HPOP by hamster hepatocytes resulted in significantly higher mutation frequencies than that by rat hepatocytes. At an HPOP concentration of 240 microM, hamster hepatocyte metabolism yielded 83.5 TGr mutants per 10(5) V79 cells; rat hepatocyte metabolism yielded only 19.8 TGr mutants per 10(5) V79 cells. This species difference in mutagenic activation correlated well with the known potency of HPOP as a carcinogen for the hamster as compared to the rat. Since hamster pancreatic cells and subcellular fractions are known to have very limited capacity to perform the metabolic activation of HPOP, the results of this study imply that liver metabolism plays an important role in the conversion of HPOP to an agent(s) which subsequently affects the hamster pancreas. The mutagenic potency of BOP versus HPOP was compared after metabolism by hepatocytes from both species. Following their metabolism by hamster hepatocytes, the two compounds were nearly equivalent in mutagenic potency. After metabolism by rat hepatocytes, BOP was significantly more potent mutagen than HPOP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3113725 TI - Production of growth factors by human myeloma cells. AB - Using in vitro-growing myeloma cell lines, we studied the growth factors involved in human multiple myeloma, and particularly the potential of autocrine secretion and response to B-cell growth factor (BCGF) of RPMI 8226, the best-documented Epstein-Barr virus-negative human myeloma cell line. We found that three myeloma cell lines (RPMI 8226, U266, and IM9) produce an autostimulatory growth factor (AGF) and thus increase their own proliferation by 2- to 3-fold in cells cultured at low density. Optimal AGF production was obtained after 24 h of culture at a cell density ranging from 2.5 to 5 million cells/ml. The three myeloma cell lines produce type II BCGF, able to induce the proliferation of highly purified human peripheral blood B-cells, only after anti-mu activation. The BCGF produced by RPMI 8226 can be absorbed onto RPMI 8226 cells together with the RPMI 8226 AGF, and the two are copurified on gel filtration in a peak with an apparent molecular weight of 70,000. RPMI 8226 can be efficiently activated by human high molecular weight BCGF II (Mr 50,000) and less extensively by BCGF I (Mr 12,000). RPMI 8226 does not produce either detectable IL1 or interferons gamma and alpha and IL1 and gamma-IFN had no stimulating effect on RPMI 8226 proliferation. Our findings support the conclusion that RPMI 8226 produces a BCGF II working as an AGF. PMID- 3113726 TI - Effects of ionizing radiation and pretreatment with [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles. AB - To assess the effects of a gonadotropin-releasing hormone agonist, [D-Leu6,des Gly10] luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance. PMID- 3113727 TI - Effects of various oxygenation conditions on the enhancement by Fluosol-DA of melphalan antitumor activity. AB - The cytotoxicity of melphalan toward exponentially growing FSaIIC fibrosarcoma cells under hypoxia, normal aeration, hyperoxygenation, and stationary phase normally oxygenated cells was examined. Through 4 logs of cell kill by melphalan, there was no difference in survival of FSaIIC cells under any of the four conditions. In the fifth and sixth logs of cell kill, melphalan was most cytotoxic toward normally aerated cells. DNA alkaline elution was performed in FSaIIC cells treated for 1 h with melphalan under the various atmospheres. Both upon immediate elution and after a 6-h delay period the greatest number of DNA cross-links were formed in the normally oxygenated cells. Tumor growth delay studies of the FSaIIC fibrosarcoma treated with melphalan were performed under four levels of oxygenation. From air breathing to 100% oxygen at 3 atm, the tumor growth delay produced by melphalan increased from about 3 days to about 9 days. With the addition of Fluosol-DA, there was an increase in tumor growth delay by melphalan from about 6.5 days with air breathing to about 13 days with 100% oxygen at 3 atm (1 h). When FSaIIC fibrosarcoma tumors were treated with melphalan, and tumor cell survival was measured by colony formation in culture, increasing doses of melphalan produced increasing levels of tumor cell kill in a relatively log linear manner. The addition of Fluosol-DA to treatment with melphalan produced approximately 1 log greater tumor cell kill than melphalan and air breathing under the various oxygenation conditions. There was approximately a 4-fold increase in toxicity to bone marrow granulocyte-macrophage colony-forming units under both extended carbogen breathing conditions (6 h) and hyperbaric oxygenation conditions (100% oxygen, 1 h, 3 atm). The response of the spleen to these various treatment regimens appeared to be immediate and shortlived. Necrotic cells were seen on day 1 posttreatment, with a substantial reduction by day 4 posttreatment. Mitotic figures were essentially absent from the liver on day 1 posttreatment, but by day 4 were significantly increased in treatment groups receiving Fluosol-DA, with the largest number seen in the melphalan/Fluosol-DA with carbogen-breathing group. In conclusion, Fluosol-DA and 1 h of carbogen breathing significantly increases the antitumor activity of melphalan without a concomitant increase in normal tissue toxicity. Although increasing the oxygenation level increased the response of the tumor, normal tissue toxicity was also increased. PMID- 3113728 TI - Pharmacokinetics of hexamethylmelamine in intralipid following hepatic regional administration in rabbits. AB - Hexamethylmelamine (HMM) is a cytotoxic agent demonstrated to have broad antitumor activity. Poor solubility in aqueous media has precluded significant evaluation of parenteral administration of this drug. A formulation of HMM dissolved in Intralipid has demonstrated excellent tolerance following parenteral administration. The goal of this study was to evaluate the pharmacology of HMM in Intralipid following hepatic regional administration. The routes of administration were intraarterial via the hepatic artery with and without arterial occlusion, i.v. via the portal and jugular veins, and i.p. All animals received a total dose of 10 mg HMM/kg of body weight. Hepatic extraction of HMM was most evident via the portal vein (PV) route [AUC(PV)/AUC(i.v.) = 0.5; P less than 0.05]. Lower plasma levels and areas under the curve (AUCs) were observed for the hepatic artery and hepatic artery-stop flow groups when compared to i.v., but the difference was not significant. Administration i.p. yielded low plasma levels but a very long half-life (88 min). Hepatic tissue levels were highest in the group receiving HMM by the hepatic artery-stop flow route. We conclude that the HMM-Intralipid mixture is well tolerated, that HMM is extracted to a significant degree by the liver following PV administration, and that an i.p. installation of HMM-Intralipid results in prolonged plasma drug levels. This preclinical study supports further efforts at evaluation of parenteral administration of the HMM-intralipid mixture. PMID- 3113729 TI - Contribution of prednisone to the effectiveness of hexamethylmelamine in multiple myeloma. AB - The Eastern Cooperative Oncology Group evaluated hexamethylmelamine in 89 patients with advanced refractory or relapsing multiple myeloma. Hexamethylmelamine was initially used as a single agent administered orally at 200 mg/m2/day for the first 3 weeks of each 4-week cycle. When this regimen proved to be ineffective, it was modified first by increasing the dose of hexamethylmelamine to 280 mg/m2/day and subsequently by adding prednisone at 75 mg for the first 7 days of each 28-day cycle. None of the 39 patients receiving hexamethylmelamine without prednisone had an objective response, while two patients had minimal objective improvement (25%-50% decrease in M protein with symptomatic improvement). Only 14% of these patients had objective or symptomatic response or both. In contrast, patients treated with hexamethylmelamine plus prednisone had a 22% objective response rate, with another 14% showing lesser degrees of objective improvement. Fifty-one percent of the patients treated with this regimen had either objective or symptomatic improvement or both. Severe (grade 3) toxicity was seen in nearly two-thirds of the patients on the higher dose hexamethylmelamine regimens compared with 37% of the patients receiving low dose hexamethylmelamine; however, in most instances this represented rapidly reversible cytopenias. Because all but one of the patients responding to hexamethylmelamine plus prednisone had experienced previous treatment failure on regimens containing prednisone in similar dose and schedules, it is unlikely that the responses are due to prednisone alone. Instead, this study suggests that the activity of hexamethylmelamine in multiple myeloma is dependent on the concomitant administration of prednisone and that the combination regimen appears to be synergistic. PMID- 3113730 TI - Phase II study of recombinant interferon-gamma in patients with disseminated malignant melanoma. AB - Twenty-eight patients with disseminated malignant melanoma received daily im therapy with recombinant interferon-gamma. The dose was 0.25 mg/m2 on Days 1-7 followed by a daily dose of 0.5 mg/m2 if tolerated. Among 27 patients, we observed three objective partial regressions (8.3, 3.7, and 3.9+ months). The median leukocyte count nadir was 2.5 X 10(3)/mm3 (range, 1.4-5.1). Constitutional symptoms included moderate to severe fever greater than 37 degrees C (100%), fatigue (59%), chills (37%), and mild to moderate myalgias (64%). Recombinant interferon-gamma produces manageable side effects but limited efficacy as employed in this study. PMID- 3113731 TI - [Effects of calcium antagonists on intracellular calcium deposits]. PMID- 3113733 TI - [Schistosomiasis japonicum and colon cancer--an inquiry about the pathogenesis of colon cancer by using the logistic regression model]. PMID- 3113732 TI - Inhibition of polyamine synthesis reduces the growth rate and delays the expression of differentiated phenotypes in primary cultures of embryonic mesoderm from chick. AB - Inhibition of polyamine synthesis in early chick embryos blocks their development at gastrulation. Analyses of arrested embryos show that mesodermal outgrowth and differentiation are drastically impaired. To study these effects in greater detail, we have used primary cultures of embryonic mesoderm from chick. The cultures were treated with alpha-difluoromethylornithine (DFMO), an enzyme activated irreversible inhibitor of ornithine decarboxylase, the first and rate limiting enzyme in polyamine synthesis. In control culture medium, mesodermal cells retained their in ovo outgrowth behavior and differentiation pattern. Addition of 10 mM DFMO to the culture medium, however, retarded attachment and outgrowth, and reduced the rate of proliferation of the mesodermal cells. Furthermore, the expression of differentiated phenotypes, such as beating heart tissue, erythroid cells, and adipocyte-like cells, was delayed. Simultaneous addition of 100 microM putrescine prevented or reduced the effects of DFMO, showing that these were indeed caused by polyamine deficiency. In the DFMO treated mesoderm, DNA synthesis was markedly suppressed by the first day. Similar effects on RNA and protein synthesis developed at a later time. Our data suggest that a reduction in the concentrations of the polyamines decreases the rate of mesodermal cell proliferation, and as a consequence delays the expression of differentiated phenotypes. PMID- 3113734 TI - [A cellulose acetate membrane immunodiffusion (CAMID) test for identification of the host source of mosquito blood meals]. PMID- 3113735 TI - [Advances in the research on non-A, non-B hepatitis]. PMID- 3113736 TI - Eukaryotic RNA polymerase I promoter binding is directed by protein contacts with transcription initiation factor and is DNA sequence-independent. AB - RNA polymerase I binding to the eukaryotic ribosomal RNA gene promoter transcription initiation factor (TIF) complex was examined by in vitro transcription and footprinting of a series of spacer mutants. Polymerase binds efficiently to the TIF-promoter complex independently of the DNA sequence in the polymerase interaction region and initiates transcription a fixed distance downstream of the TIF binding site on AT-rich templates. Methidiumpropyl EDTA.FE(II) footprinting confirms minimal contacts between polymerase and DNA. We infer that polymerase is directed to the promoter by a DNA sequence-independent mechanism, solely by protein-protein contacts with TIF. An initiation step subsequent to binding requires special sequence characteristics in the transcription start site region. PMID- 3113737 TI - A thousand and one protein kinases. PMID- 3113738 TI - The yeast SCG1 gene: a G alpha-like protein implicated in the a- and alpha-factor response pathway. AB - We have identified the SCG1 gene by its ability to suppress the pheromone supersensitive sst2-1 mutation. The nucleotide sequence of SCG1 suggests that it encodes a 54 kd protein homologous to the alpha subunit of the vertebrate G proteins transducin, Gs, Gi, and Go. SCG1 expression and function are haploid specific; haploid scg1 cells grow into very small colonies consisting of large, abnormally shaped cells, whereas a/alpha scg1/scg1 diploids show wild-type morphology, growth, and sporulation. We postulate that the SCG1 product is involved in the pheromone response pathway, and propose two models for the function of the SCG1 product. Expression of the rat alpha s gene in yeast partially complements both the sst2 and scg1 defects, indicating a high level of conservation of sequence and function between SCG1 and mammalian G alpha subunits. PMID- 3113739 TI - GPA1, a haploid-specific essential gene, encodes a yeast homolog of mammalian G protein which may be involved in mating factor signal transduction. AB - GPA1 protein of Saccharomyces cerevisiae is homologous to the alpha subunit of mammalian G protein. GPA1 transcript was found in haploid cells but was not detected in diploid cells. Disruption of GPA1 resulted in a haploid-specific lethal phenotype, indicating that GPA1 is a haploid-specific essential gene for cell growth. Upon regulation of expression of GPA1 by the galactose-inducible GAL1 promoter, the loss of GPA1 function was found to lead to cell-cycle arrest at the late G1 phase. Mutants that suppress the lethality of the gpa1::HIS3 mutation showed a sterile phenotype that was not cell-type-specific. These results suggest that GPA1 protein may control the signal for mating-factor mediated cell-cycle arrest. PMID- 3113740 TI - Disconnected: a locus required for neuronal pathway formation in the visual system of Drosophila. AB - Mutations at the X-linked disconnected locus of D. melanogaster lead to the failure of adult photoreceptor axons to innervate their target cells in the developing optic lobes of the third instar larva, resulting in flies that have rudimentary optic ganglia. The cascade of epigenetic events leading to the adult disconnected phenotype is caused by the misrouting of a larval pioneer nerve, Bolwig's nerve, during embryonic development. In the disconnected mutant this nerve fails to recognize and establish stable connections with its correct synaptic partners. In addition, disconnected affects both the proper aggregation and the movement of the Bolwig neurons to their final location in the embryo. Finally, similar but more subtle defects can be found in a subset of other peripheral neurons in the thoracic and abdominal segments. The different aspects of the phenotype suggest that the disconnected gene plays a role in neuronal cell recognition. PMID- 3113741 TI - Lysis of fresh solid tumor targets in the presence of Con A is mediated primarily by Leu 7+ peripheral blood T lymphocytes: blocking by the anti-CD3 monoclonal antibody and comparison with recombinant interleukin 2-induced lysis by natural killer cells. AB - We investigated the lysis of fresh human solid tumor cells by peripheral blood T lymphocytes in the presence of lectins and anti-CD3 monoclonal antibodies (mAb). Addition of certain lectins (Con A, PHA, or WGA) directly into the 4-hr 51Cr release assay caused significant lysis of (P less than 0.001) noncultured solid tumor targets by enriched populations of granular lymphocytes (GL). Significant levels (P at least less than 0.001) of Con A- or PHA-dependent solid tumor lysis by GL-enriched lymphocytes were observed in 32 of 39 donors (82%) and 14 of 20 donors (70%), respectively. In contrast, the addition of other lectins (PNA, PWM, or LPS) or anti-CD3 mAb did not cause cytotoxicity. The levels of Con A-dependent lysis were comparable to those of interleukin 2 (IL-2)-induced lysis by Leu 11b+ natural killer (NK) cells. The presence of lectins at the effector phase, but not of recombinant IL-2 (rIL-2), was required for the lysis of solid tumor targets. Both Con A-dependent and rIL-2-induced lysis were totally inhibited by treatment of the effector cells with the lysosomotropic agent L-leucine methyl ester (LeuOMe). Effector cells responsible for Con A-dependent lysis of solid tumors expressed T3 (CD3), T8 (CD8), and Leu 7 antigens, but lacked T4 (CD4) and Leu 11 (CD16) antigens as determined by both negative and positive cell selection studies. Con A-dependent lysis was inhibited at the effector phase by anti-CD3 (OKT3 or anti-Leu 4) or anti-CD2 (OKT11) mAb. On the basis of their phenotype (Leu 7+ CD3+ CD8+ CD16-), we hypothesize that these effector cells may contain a population of cytotoxic T cells (CTL) generated in vivo against autologous modified cells that can lyse fresh solid tumor target cells under conditions where the recognition requirements for the CTL are bypassed by lectin approximation. PMID- 3113742 TI - Spontaneous human T-cell cytotoxicity against murine hybridomas expressing the OKT3 monoclonal antibody: comparison with natural killer cell activity. AB - Human peripheral blood lymphocytes (PBL) exhibited spontaneous cytotoxicity against OKT3 monoclonal antibody (mAb)-expressing murine hybridoma cells (OKT3 hybridomas). In contrast, other murine hybridomas expressing OKT4, OKT8, anti-HLA DR, and anti-HLA A, B, and C mAb were not lysed. PBL showed much lower levels of cytotoxicity (3 folds) against OKT3 hybridomas as compared with NK activity against the K562 targets. Lymph node (LN) cells exhibited the inverse relationship of cytotoxicity levels. The addition of OKT3 mAb to the effector cells totally blocked both the binding and the lysis of OKT3 hybridoma targets, indicating that the CD3 antigen on the effector cells may be involved in recognition of the targets. The addition of concanavalin (Con A) also inhibited the cytotoxicity of OKT3 hybridomas. OKT4 mAb-expressing hybridomas became susceptible to lysis after chemical attachment of OKT3 mAb with CrCl3. The kinetics of lysis of OKT3 hybridomas resembled that of NK activity. Both cytotoxicities were detectable after 1 to 2 hr and reached plateau levels by 4 to 6 hr. Effector cells responsible for lysis of OKT3 hybridomas expressed T3, T8, and Leu 7 antigens, but lacked T4 and Leu 11b antigens, and were sensitive to the treatment with L-leucine methyl ester. These results indicate that T3+, T8+, Leu 7+ and T4-, and Leu 11- granular lymphocytes have a spontaneous cytotoxic activity against OKT3 hybridomas which is different from classic NK activity. These findings may provide a method for the assessment of T-cell cytotoxicity mediated presumably by in vivo generated cytotoxic T lymphocytes in blood and the other immune organs. PMID- 3113743 TI - Expansion of tumor-specific cytolytic T lymphocytes using in vitro restimulation with tumor-specific transplantation antigen. AB - Tumor-specific T lymphocytes (CTL) induced by in vivo immunization of C3H/HeJ mice with the syngeneic methylcholanthrene (MCA)-induced fibrosarcoma MCA-F were expanded in vitro by restimulation with 1-butanol-extracted, isoelectrophoretically purified, tumor-specific transplantation antigen (TSTA) in combination with purified rat interleukin-2 (IL-2) and fresh, syngeneic, 2000-R irradiated, adherent splenic antigen-presenting cells (APC). The cultured immune T-cell population, containing 40-55% Lyt 2+ and 40-60% L3T4+ cells, displayed TSTA-specific proliferative and cytotoxic activities in vitro. The expanded T cells appear to recognize butanol-extracted TSTA in association with specific H-2 class I antigens, as revealed by the benefit of syngeneic over allogeneic cells as APC and by the adverse effect of depletion using anti-H-2K, but not anti-Ia, monoclonal antibodies. In adoptive transfer assays in vitro, expanded T cells specifically neutralize homotypic, but not heterotypic, tumor growth in vivo. Based upon the effects of depletion of T-lymphocyte subpopulations using monoclonal antibodies, the Lyt 2+ cytotoxic T lymphocytes (CTL) appear to display greater in vivo neutralizing activity than L3T4+ T cells. Thus in vitro stimulation of in vivo-immunized T cells, using butanol-extracted TSTA in combination with IL-2 and syngeneic APC, expands tumor-specific CTL. PMID- 3113745 TI - Impact of gonadotropin (FSH-LH)-thyrotropin (TSH) overlap on the growth of Chinese hamster ovary (CHO) cell culture after single and repeated treatment. PMID- 3113744 TI - Monocyte- and natural killer cell-mediated spontaneous cytotoxicity against human noncultured solid tumor cells. AB - Unstimulated human peripheral blood mononuclear cells from healthy donors exhibited spontaneous cytotoxicity against noncultured solid tumor targets in a 12- to 24-hr 51Cr release or 111In release assay. Both purified monocytes (greater than 99% monocytes) and natural killer (NK)-enriched lymphocytes exhibited comparable levels of spontaneous cytotoxicity against fresh melanoma tumor targets. This cytotoxicity was observed under endotoxin-free conditions. NK depleted lymphocytes did not lyse the melanoma targets. Culture supernatants of monocytes incubated with the melanoma tumor cells did not exhibit cytotoxic activity against these targets. Purified monocytes lacked NK activity against the K562 targets in a 4-hr 51Cr release assay. Treatment of the monocytes with anti Leu 1 1b and anti-Leu7 monoclonal antibodies plus complement did not reduce monocyte-mediated lysis of the melanoma targets, demonstrating that contaminating NK cells, if any, were not responsible for the lysis of noncultured melanoma targets by monocytes. In contrast, Leu 1 1b+ NK cells were responsible for the lysis of the melanoma targets by NK-enriched lymphocytes. The addition of recombinant interferon-gamma (rIFN-gamma), but not lipopolysaccharide, into the 51Cr release assay or pretreatment of monocytes with rIFN-gamma significantly increased their cytotoxicity against noncultured solid tumor cells. Monocytes cultured for 3 days with medium alone lost their cytotoxic activity. The addition of rIFN-gamma from the beginning of these cultures prevented the loss of the cytotoxic activity of monocytes. In summary, both unstimulated monocytes and NK enriched lymphocytes exhibit comparable levels of spontaneous cytotoxicity against fresh solid tumor targets. PMID- 3113746 TI - Selective inducibility of microsomal cytochrome b560ms in Tetrahymena. PMID- 3113747 TI - DNA synthesis in isolated nuclei from synchronized plasmodia of Physarum polycephalum. AB - Nuclei were isolated from synchronized plasmodia of a true slime mold, Physarum polycephalum, in S-phase, and DNA synthesis in the nuclei was studied in vitro. The nuclei catalyzed DNA synthesis at the rate of 0.7 ng DNA/1.0 X 10(6) nuclei/30 min at 25 degrees C, which was 5 times higher than that catalyzed in G2 phase nuclei. The DNA synthesis required Mg2+, four kinds of deoxyribonucleoside 5'-triphosphates and ATP, suggesting that the mode of synthesis is a replicative type, but not a repair-one. Sedimentation analysis of the DNA products revealed that the nuclei produced 2-4S DNA fragments mainly during a 30-sec pulse incubation, and 2-4S, 5-12S and longer fragments during a 15-min incubation. The pulse- and chase-labeling experiments showed that the 2-4S fragments shifted discontinuously to longer fragments. These results indicate that the nuclei catalyze the formation of 2-4S Okazaki fragments first and then their subsequent ligation. Eighty % and 96% of the DNA synthesis was inhibited by 200 micrograms/ml aphidicolin and 40 mM N-ethylmaleimide, respectively, but 80% of the activity was resistant to 100 microM 2',3'-dideoxythymidine 5'-triphosphate. These results suggest that the DNA synthesis is catalyzed by the alpha-type DNA polymerase of Physarum polycephalum. PMID- 3113748 TI - Cytochalasin B enhances T cell mitogenesis by promoting expression of an interleukin 2 receptor. AB - Low concentrations of cytochalasin B enhanced the T cell mitogenesis induced by concanavalin A (Con A) and interleukin 2 (IL-2). Mitogenesis was augmented by cytochalasin B given in the Con A-dependent early phase, or through T cell mitogenesis. Cytochalasin B did not enhance T cell mitogenesis when given only in the IL-2-dependent late phase. Use of the monoclonal antibody that directs the IL 2 receptor showed that cytochalasin B increased the expression of the IL-2 receptor induced by Con A. We concluded that cytochalasin b acts on an early phase of T cell mitogenesis and augments the expression of IL-2 receptor which enables certain nonresponsive T cells to respond to IL-2. PMID- 3113749 TI - Calcium ion influx during mitogenic stimulation of lymphocytes. AB - The uptake of free calcium ion (Ca2+) in PHA- or A23187-stimulated lymphocytes was measured using 45CaCl2 and 3H-water. Augmentation of Ca2+ uptake by both mitogens was observed, but the enhanced uptake occurred transiently, sometime within 30 min of the stimulation. The total amount of calcium in quiescent lymphocytes as determined by atomic absorption spectroscopy was about 2.9 X 10( 15) g/cell. When stimulated with PHA, more calcium gradually accumulated in the cells. The maximum amount of accumulation occurred at around 40 h, and was about 2-fold higher than that of control cells. In A23187-stimulated cells, the calcium content increased within 1 h by about 4-fold, reached a maximum at about 6 h (6 fold) and thereafter, surplus calcium was pumped out. The cytosolic free calcium ion concentration (the [Ca2+]i) within single cells was measured using quin 2 or fura-2. The [Ca2+]i was about 1 X 10(-7) M, and a transient increase in the [Ca2+]i was observed in some cells within 1 min after Con A-stimulation. Another rise in the [Ca2+]i was observed around the 40th h, and the maximum expression of the IL-2 receptor was observed at about this time. Therefore the results may indicate that the IL-2-mediated lymphocyte transformation is dependent on the rise in the [Ca2+]i. PMID- 3113750 TI - Stability of drug metabolizing enzymes during the incubation conditions of the liver microsomal assay with non-induced and induced mouse liver S-9 fractions. AB - The purpose of this work was to study the relative activities and stabilities of phase-I and phase-II drug metabolizing enzymes in incubation mixtures used in vitro genotoxicity testing in order to optimize the conditions of the assay, increase sensitivity and eliminate false negative results. Cytochrome P-450, NADPH-cytochrome P-450 (cytochrome c) reductase activity and various phase-I and phase-II enzyme activities of the drug-metabolizing system were determined in incubation mixtures used in liver microsomal assays. The behaviour of aminopyrine N-demethylase and p-nitroanisole O-demethylase activities as phase-I markers have been reported previously. Other activities measured were glutathione S transferase, glutathione S-epoxide transferase and epoxide hydrase, and lipid peroxidation (LP) was determined. The experiments were carried out on liver S9 fractions derived from non-induced mice or mice induced with sodium phenobarbital (PB), and/or beta-naphthoflavone (beta-NF). The phase-II enzymes were much more stable (70-90% residual activity) than phase-I enzyme activities (35-60%) in all conditions tested. The residual cytochrome P-450 was approximately 70% stable and the remaining activity of NADPH-cytochrome c-reductase about 80%, indicating that this latter enzyme does not limit the rate of the monoxygenase system in these conditions. Phase-II enzymes were induced to a smaller extent (about 2 times) than in phase-I enzymes (5-6 times) by beta-NF + PB. NADPH-cytochrome c-reductase behaved as phase-II enzymes in this respect as well as for stability. LP was appreciably higher in non-induced than in induced animals. Treatment with the beta-NF + PB mixture, however, showed that induced enzymes were more stable than those obtained by simple induction with either beta-NF or PB alone. These results lead to the conclusion that prolonged incubation times in mutagenicity assays are unnecessary when considering the relative stabilities of the various phase-I and phase-II enzyme activities in the drug-metabolizing system. PMID- 3113751 TI - Topical treatment of mice with benzo[a]pyrene or parenteral administration of benzo[a]pyrene diol epoxide-DNA to rats results in faecal excretion of a putative benzo[a]pyrene diol epoxide-deoxyguanosine adduct. AB - The administration of [3H]BPDE-DNA, whether by i.p. or i.v. injection, to male Wistar rats resulted in the majority of the radioactivity being recovered in the faeces. Excretion was rapid: within 24 h post-injection, 45% of the applied dose was recovered in the faeces. H.p.l.c. analysis of radioactive material extracted from the faeces by methanol showed that it contained a single component which co chromatographed with [3H]BPDE-dGuo and which was not affected by treatment with alkaline phosphatase, aryl sulphatase or beta-glucuronidase. To determine if this phenomenon occurs after topical application of BP to a target tissue, such as mouse skin, animals were treated with [3H]BP and their faeces collected. After an extensive extraction procedure involving differential solubility in organic solvents, Sephadex LH-20 chromatography and h.p.l.c., a product was isolated from mice faeces which had characteristics consistent with a [3H]BPDE-dGuo adduct. These findings are discussed in relation to detection of BPDE adducts in human populations. PMID- 3113752 TI - An evaluation of the effects of culture medium osmolality and pH on metabolic cooperation between Chinese hamster V79 cells. AB - The Chinese hamster V79 cell metabolic cooperation assay indirectly measures an inhibition of intercellular communication through gap junctions and can detect many tumor promoters. The experiments described here were designed to determine whether culture medium osmolality and pH affect the endpoint of this assay, since hypertonic solutions and cytoplasmic acidification can uncouple gap junctions in other systems. Hypertonic concentrations of sucrose and mannitol in medium did inhibit metabolic cooperation, but these solutes were active over different ranges of osmolalities. In similar experiments, sodium chloride, choline chloride and sodium glucuronate had no effect on metabolic cooperation. Furthermore, data were obtained indicating that osmotic effects are not likely to contribute to the inhibition of metabolic cooperation by sodium saccharin. It is concluded that hypertonic culture conditions do not necessarily cause an inhibition of metabolic cooperation, and the properties of an added solute are important in determining the effects observed. Additionally, it was found that buffering the culture medium pH between approximately 6.6 and 7.7, during the period when test substances are normally present, had no effect on metabolic cooperation. PMID- 3113753 TI - The binding efficiency of polyclonal and monoclonal antibodies to DNA modified with benzo[a]pyrene diol epoxide is dependent on the level of modification. Implications for quantitation of benzo[a]pyrene-DNA adducts in vivo. AB - A number of polyclonal antibodies specific for DNA modified with (+/-)trans-7,8 dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyre ne (BPDE) were obtained from the sera of New Zealand white rabbits immunized with BPDE-DNA, complexed with methylated bovine serum albumin (mBSA). Monoclonal antibodies were developed by fusion of mouse myeloma cells with spleen cells isolated from BALB/c mice immunized with the same complex of BPDE-DNA and mBSA. These antibodies have been characterized for specificity in a highly sensitive, enzyme-linked immunosorbent assay (ELISA). All antibodies showed a very high affinity for single-stranded BPDE-DNA, but had lower affinity towards native BPDE-DNA. The affinity for the free mononucleoside BPDE-dG was at least 100-fold lower than that for BPDE-DNA, and no affinity was detected for BP tetrols or DNA modified with N-acetoxy-N acetyl-2-aminofluorene. A high cross reactivity was observed with DNA modified with (+/-)-trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydrochrysene++ +. Using five different antibodies, monoclonal or polyclonal, we observed that the antibody affinity for BPDE-DNA was dependent on the level of modification; in the competitive ELISA as little as 4 fmol BPDE-DNA (50 pmol/micrograms) was sufficient for 50% inhibition with our best antisera, but 17 fmol of the adduct was required when [3H]BPDE-DNA of low modification (1-10 fmol/micrograms) was used as inhibitor. When samples of [3H]BP-DNA isolated from the livers of mice, treated i.p. with different doses of [3H]BP were examined by competitive ELISA and calibrated with [3H]BPDE-DNA of low modification (1-10 fmol/micrograms), binding values calculated from the immunoassay were in good agreement with those obtained from radioactivity measurements. In contrast, when this DNA was quantitated in competitive ELISA using highly modified BPDE-DNA as standards, values by ELISA were 20-40% of those obtained by radioactivity. These results indicate that the use of serially diluted BPDE-DNA of high modification as standard competitor in the ELISA will lead to erroneous results in the measurement of adducts in DNAs modified to a low extent (biological samples). The property of antisera specific for BP-DNA, recognizing highly modified DNA more efficiently than DNA modified to a low extent, may be common to all antisera elicited against highly modified DNA immunogens. Therefore we conclude that antibody affinity must be tested also with DNA samples of low modification, obtained either in vitro or in vivo. PMID- 3113754 TI - Response of mammalian ADP-ribosyl transferase to lymphocyte stimulation, mutagen treatment and cell cycling. AB - The inhibitors of the nuclear enzyme ADP-ribosyl transferase (ADPRT) had been shown to block the stimulation of quiescent lymphocytes with mitogens suggesting the involvement of the enzyme in the control of gene expression and cell differentiation. By means of the activity-gel assay we have analysed the intensity and the molecular mass of the catalytic bands of the enzyme at early and late times after stimulation of human lymphocytes by phytohemagglutinin. We observed that the increase in the activity of ADPRT is concurrent with the onset of DNA synthesis and is maintained for up to 10 days after lymphocyte stimulation, when DNA replication is over but the capacity to perform repair synthesis is still elevated. The analysis of ADPRT in stimulated lymphocytes by Western blots indicated that the increase in enzyme activity is due to the de novo synthesis of enzyme protein. The response of ADPRT to the treatment of human lymphocytes with DNA-damaging agents was studied at various dose-ranges, using the activity-gel technique. The results obtained indicate that dimethyl sulfate is 10 times as active as methyl methane sulfonate in stimulating ADPRT activity and that, at very high doses, the activity band of the enzyme tends to disappear. Very similar observations were obtained when Chinese hamster ovary cells were treated with the same agents, although the concentrations of the mutagens eliciting maximal ADPRT activation were 10 times higher than in human lymphocytes. When analysed by Western blots, no significant difference of the protein band of the enzyme was observed in comparing control and treated cells. This suggests that the activity-gel system can detect two different phenomena: the increase in enzyme protein, as in the case of stimulated lymphocytes, and the enzyme-activating effect of DNA-damaging agents, which occurs without changing the number of enzyme molecules. Of particular interest is the observation that mitomycin C is capable of activating ADPRT in human lymphocytes, thus suggesting that cross-linking agents are involved in promoting ADP-ribosylation reactions. We have also analysed the variations of the enzyme throughout the cell cycle in HeLa cells synchronized in S phase or in mitosis. No significant changes in the levels of the enzyme activity were revealed by the activity-gel assay during the progression of the cycle, although an overall increase of active polypeptides of larger size in concomitance with the S period was observed. PMID- 3113755 TI - Influence of disulfiram on the metabolism of the urinary bladder carcinogen N butyl-N-(4-hydroxybutyl)nitrosamine in the rat. AB - The effect of feeding disulfiram (DSF) to rats on the metabolism of N-butyl-N-(4 hydroxybutyl)nitrosamine (BHBN) was examined in order to study the mechanism by which DSF inhibits bladder cancer induction by BHBN. After 2 weeks of feeding 0.5% DSF in the diet, animals were given [14C]BHBN (25 mg/kg) and the urine and expired CO2 were collected for 8 h. Radioactivity in expired air was very low, but DSF caused a significant reduction in expired 14CO2 (control 1.0% of dose; DSF 0.6%), presumably by inhibition of alpha-hydroxylation pathways. There was no difference in the excretion of total urinary radioactivity (control 84%; DSF 85%). Urine was analyzed by h.p.l.c. for BHBN, N-butyl-N-(3 carboxypropyl)nitrosamine (BCPN), N-butyl-N-2-hydroxy-3-carboxypropyl)nitrosamine (BHCPN) and N-butyl-N-carboxymethylnitrosamine (BCMN). DSF did not alter the urinary excretion of BCPN (control 64% of dose; DSF 61%), whereas BHCPN excretion was increased (control 11% of dose; DSF 22%) and urinary levels of BCMN were decreased (control 10% of dose; DSF 4%). The metabolism of BHBN was also studied in isolated hepatocytes from control and DSF-fed rats. Hepatocytes were incubated in Liebovitz's L-15 medium containing 0.5 mM [14C]BHBN and aliquots of the medium were removed for h.p.l.c. analysis at 0.5, 1, 2 and 4 h. Metabolic rates are expressed as mumol/h/5 million cells. There was no difference in the overall rate of metabolism of BHBN in control and DSF-fed rats. BHBN was very rapidly oxidized to BCPN and the rate was not affected by DSF treatment (control 1.82; DSF 1.76). The rate of accumulation of BHCPN was increased 3.5-fold in the DSF-fed rats (control 0.06; DSF 0.21) and BCMN could not be detected. Taken together, these data show that (i) DSF may inhibit the low extent of alpha-hydroxylation of BHBN or BCPN; (ii) DSF does not inhibit the rapid oxidation of BHBN to BCPN and (iii) DSF appears to inhibit the metabolism of BHCPN. PMID- 3113756 TI - X-ray refinement of the crystal and molecular structure of 1,12 dimethylbenz[a]anthracene. AB - The molecular and crystal structure of 1,12-dimethylbenz[a]anthracene, one of the least carcinogenic of the benz[a]anthracenes, has been refined, from new X-ray diffractometric data collected at room temperature, to an R index 0.047 over 1217 independent reflections. Improved determination of molecular geometry shows that steric strain arising from the presence of two bay-methyl substituents causes even greater molecular distortion than in the highly carcinogenic 7,12 dimethylbenz[a]anthracene, with the benzo A ring inclined at about 29 degrees to the furthest C and D rings. Methyl carbon atoms are displaced 1.0 and 1.3 A on opposite sides of the mean molecular plane and the beach bond of the bay region is 1.480(4) A long, flanked by C-C-C angles of 124.3 and 125.0 degrees. The shortest carbon-carbon bond is C5-C6 = 1.327(5) A at the K region, with the next shortest C8-C9 = 1.346(6) A. Close intramolecular approaches of methyl hydrogens across the bay and to nearest aromatic hydrogens are 2.3-2.6 A. PMID- 3113757 TI - Oleic acid induces pulmonary injury independent of eicosanoids in the isolated, perfused rabbit lung. AB - Intravenous injection of oleic acid (OA) induces acute, edematous lung injury resembling some of the features of adult respiratory distress syndrome. One class of inflammatory agents speculated to be mediators of acute lung injury are eicosanoids. We tested the hypothesis that 5-lipoxygenase and cyclooxygenase metabolites of arachidonic acid mediate the pulmonary injury induced by OA. OA (0.1 ml), injected as a bolus into the pulmonary artery (PA) of isolated, Krebs perfused rabbit lungs, resulted in significant (P less than .05) increases in lung weight (an index of pulmonary edema), maximum airway pressure, perfusate immunoreactive (i) 6-keto PGF1a, and a significant, though minimal, increase in perfusate i-thromboxane B2. No measurable increases were recorded in PA pressure or perfusate i-leukotriene (LT) C4/D4. Neither pretreatment with the LTD4/E4 antagonist, LY171883 (10 microM), nor the 5-lipoxygenase/cyclooxygenase inhibitor, BW755C (100 microM), attenuated the pulmonary edema. However, BW755C abrogated the increase in i6-keto PGF1a. Additionally, administration of exogenous LTD4 (100 nM) into the perfusate produced only a minimal increase in lung weight in the isolated rabbit lungs (n = 4). These results demonstrate that 5-lipoxygenase and cyclooxygenase metabolites do not appear to mediate OA-induced injury in the isolated, Krebs-perfused rabbit lung. PMID- 3113758 TI - Use of kappa and lambda chain quantitation for the detection of immunoglobulin abnormalities in serum. AB - Quantitation of kappa and lambda light chains was investigated as an alternative to immunoelectrophoresis or immunofixation in the analysis of sera for abnormal immunoglobulins. Normal values for the ratios of total immunoglobulins to total light chains, and for total kappa chains to total lambda chains, were established in 104 control sera and were 1.070 +/- 0.074 and 1.770 +/- 0.337, respectively. Protein electrophoresis plus quantitation of immunoglobulin heavy and light chains provided sufficient data for the analysis of 79% of apparent normal sera, 76% of apparent abnormal sera which did not have monoclonal components, 73% of abnormal sera which contained monoclonal components, and 53% of pediatric sera. However, this protocol failed to detect monoclonal components known to be present in two sera. These data indicate that this analytic approach cannot replace the subjective analysis of sera by immunoelectrophoresis or immunofixation. PMID- 3113759 TI - Use of whole blood methods in assessment of immune parameters in immunodeficiency states. AB - Whole blood (WB) methods requiring less than 4 ml heparinized peripheral blood were used to define mononuclear cell phenotype, lymphocyte proliferation, and natural cell-mediated cytotoxicity (CYT) in samples from normal controls and patients with immunodeficiency states of acquired immunodeficiency syndrome (AIDS) and AIDS-related complexes (ARC). Results from two-color direct immunofluorescence staining of blood samples with monoclonal antibodies (Mabs) conjugated to phycoerythrin (PE) or to fluorescein isothiocyanate (FITC) and flow cytometry for the determination of mononuclear cells reactive with T11, T4, T8, B1, and NKH.1 surface markers were compared to one-color indirect immunofluorescence analysis with unlabeled Mabs and FITC-labeled goat anti-mouse IgG and flow cytometry. We found that two-color analysis was as sensitive as one color analysis in detecting abnormal subset distribution in the patient groups. Functional properties of mononuclear cells (MNC) in WB samples and after density gradient separation were studied by mitogen-induced lymphocyte proliferation and CYT. Although the means of the groups studied varied depending on method used, results using WB methods clearly delineated the expected differences between the immunodepressed patients and normal subjects. The effects of sample storage on results obtained with WB methods for surface marker analysis, lymphocyte proliferation, and natural killer activity were also examined. PMID- 3113760 TI - Porcine coronary arteries with regenerated endothelium have a reduced endothelium dependent responsiveness to aggregating platelets and serotonin. AB - To test the ability of regenerated endothelium to evoke endothelium-dependent relaxations, male Yorkshire pigs underwent balloon endothelial denudation of the proximal left anterior descending coronary artery. Endothelium-dependent responses were examined in vitro, in rings of coronary segments taken from the denuded area or from the proximal left circumflex coronary artery. The experiments were performed 8 days or 4 weeks after the denudation. Endothelial regrowth was confirmed by histologic examination 8 days after the denudation and by demonstrating the presence of endothelium-dependent relaxations to bradykinin; at that time aggregating platelets evoked normal endothelium-dependent responses. However, 4 weeks after the denudation, the relaxations to aggregating platelets were markedly depressed although continuous endothelial lining was present, and the endothelium-dependent responses to bradykinin, adenosine diphosphate, the Ca2+-ionophore A23187, platelet activating factor, and thrombin were unaltered. Four weeks after denudation, endothelium-dependent relaxations to serotonin were depressed. Higher concentration of serotonin induced endothelium-dependent contractions in quiescent rings with regenerated endothelium, suggesting that regenerated endothelial cells may produce endothelium-derived constricting factor(s) and release less endothelium-derived relaxing factor(s) when exposed to the monoamine. The endothelium-dependent relaxation to serotonin was not reduced by the S2-serotonergic antagonist ketanserin but prevented by the combined S1- and S2-serotonergic blocker methiothepin. The platelet-induced relaxation was due to released serotonin and adenine nucleotides in control left circumflex coronary arteries, but in left anterior descending coronary artery with regenerated endothelium, it was due solely to the latter. The platelet-induced contractions were due to activation of receptors on the smooth muscle cells. Four weeks after denudation, regenerated endothelial cells were morphologically different from native cells; they were elongated and cuboidal, and the number of the cells had increased twofold. At this state, eccentric myointimal thickening was present in the previously denuded portion. These experiments indicate that the protective role of endothelial cells against the vasoconstriction induced by aggregating platelets is depressed in the chronic regenerated state. A lack of responsiveness to serotonin appears to be the cause for the endothelial dysfunction. PMID- 3113761 TI - Mechanism of histamine actions in human coronary arteries. AB - Helical strips of human coronary arteries contracted in response to histamine concentration dependently, they relaxed with low concentrations and contracted with high concentrations. Treatment with cimetidine potentiated contraction in the strips with intact and damaged endothelium to a similar extent and attenuated relaxation. Removal of endothelium abolished relaxation and potentiated contraction in the cimetidine-treated strips. Methylene blue increased the contractile response to histamine in the strips with endothelium but did not alter the response in the damaged-endothelium strips. Histamine-induced relaxations in the intact strips were suppressed or abolished by treatment with ETYA, AA861, a lipoxygenase inhibitor, and by chlorpheniramine but were unaffected by indomethacin. Chlorpheniramine also abolished amine-induced contraction. It may be concluded that histamine-induced contraction in human coronary arteries is mediated by H1 receptors in smooth muscle, and relaxation is mediated by H2 receptors in smooth muscle and H1 receptors in endothelium. Also, stimulation of the endothelial H1 receptor liberates vasodilator substance and possibly activates smooth muscle guanylate cyclase to accumulate cellular cyclic guanosine monophosphate. PMID- 3113762 TI - [Experimental infection of Sarcocystis suihominis in pigs]. PMID- 3113763 TI - New developments in lipid-lowering therapy: the role of inhibitors of hydroxymethylglutaryl-coenzyme A reductase. AB - HMG-CoA reductase catalyzes the conversion of hydroxymethylglutarate to mevalonate, an important early rate-limiting step in the cholesterol biosynthesis pathway. Since the discovery of compactin, the first HMG-CoA reductase inhibitor, by Endo et al. in 1976, several other inhibitors have been described. Those that have been investigated in the clinic include mevastatin (compactin), lovastatin (mevinolin), simvastatin (synvinolin), eptastatin (CS-514, SQ-31,000), and SRI 62320. These compounds are competitive inhibitors, with Ki values of the hydroxyacid forms of around 10(-9) M. Lovastatin (mevinolin, Mevacor), which is in the late stages of clinical development and has been administered to over 1000 subjects for up to 4 years, is the inhibitor on which the most information is available. It is given in single or divided doses of 20 to 80 mg/day, and is a very effective and usually well-tolerated lipid-lowering agent. At 40 mg bid, lovastatin produces the following approximate mean changes: total plasma cholesterol, -33%; low-density lipoprotein (LDL) cholesterol, -40%; very low density lipoprotein cholesterol, -35%; plasma triglycerides, -25%; high-density lipoprotein cholesterol, +10%; apolipoprotein B, -20%. The substantial reduction in both LDL cholesterol and apolipoprotein B (the principal protein component of LDL) indicates a reduction in the number of circulating LDL particles. The mechanism probably involves both decreased LDL production and increased LDL clearance. PMID- 3113764 TI - Incidence of early tolerance to hemodynamic effects of continuous infusion of nitroglycerin in patients with coronary artery disease and heart failure. AB - Sustained therapy with nitroglycerin (NTG) has been reported to provoke the development of early tolerance. Because continuous intravenous NTG infusion is commonly used in patients with coronary artery disease and heart failure, we evaluated the incidence of early tolerance developed within the first 24 hr of therapy in 31 responders to NTG. After documentation of response to NTG, defined as a 10 mm Hg or greater or a 30% or greater reduction in mean pulmonary arterial wedge pressure (PAWP), 16 patients were blindly, randomly assigned to receive placebo and 15 patients were continued on same-dose NTG. Both groups showed an identical fall in PAWP at peak NTG titration (11 +/- 4 mm Hg). Discontinuation of NTG in the placebo group resulted in a rapid increase in PAWP to levels not significantly different from baseline (19 +/- 5 mm Hg at 2 hr vs 23 +/- 6 mm Hg at baseline; p = NS). In the NTG group, PAWP fell from 27 +/- 9 to 14 +/- 7 mm Hg, was 16 +/- 9 mm Hg at 2 hr (p less than .05 vs baseline), and continued to be significantly lower than baseline for 8 hr; however, due to attenuation of effect, PAWP values at 12, 20, and 24 hr were not significantly different from placebo or baseline values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113765 TI - Delineation of myocardial oxygen utilization with carbon-11-labeled acetate. AB - Although positron-emission tomography (PET) with labeled fatty acid delineates infarct size and permits qualitative assessment of fatty acid utilization, quantification of oxidative metabolism is limited by complex alterations in the pattern of utilization of fatty acid during ischemia and reperfusion. Because metabolism of acetate by myocardium is less complex than that of glucose or palmitate, we characterized kinetics of utilization of radiolabeled acetate in 37 isolated rabbit hearts perfused with modified Krebs-Henseleit buffer and performed a pilot tomographic study in man. Results of initial experiments with carbon-14-labeled acetate (14C-acetate) indicated that the steady-state extraction fraction of acetate averaged 61.5 +/- 4.0% in control hearts (n = 4), 93.6 +/- 0.9% in hearts rendered ischemic (n = 4), and 54.8 +/- 4.0% in hearts reperfused after 60 min of ischemia (n = 3). Oxidation of 14C-acetate, assessed from the rate of efflux of 14CO2 in the venous effluent, correlated closely with the rate of oxygen consumption under diverse metabolic conditions (r = .97, p less than .001). In addition, no significant differences were observed between rates of efflux of total 14C in all chemical species (reflecting total clearance of tracer from myocardium) and efflux of 14CO2. Clearance of 11C-acetate, measured externally with gamma probes in normal and ischemic myocardium, correlated closely with clearance of 14C-acetate measured directly in the effluent (r = .99, p less than .001) and with overall myocardial oxygen consumption (r = .95, p less than .001). Accumulation and clearance of 11C acetate from human myocardium with PET demonstrated kinetics comparable to those seen with radiolabeled acetate in vitro. Thus externally detectable clearance of 11C-acetate provides a quantitative index of myocardial oxidative metabolism despite variation in the patterns of intermediary metabolism that confounds interpretation of results with conventionally used tracers such as glucose and fatty acid. PMID- 3113766 TI - Performance of an in-vivo, continuous blood-gas monitor with disposable probe. AB - A fluorescence-based fiber optic measurement system has been developed for monitoring pH, pCO2, and pO2 through a 20-gauge radial artery catheter without compromising capabilities for monitoring arterial pressure or for blood withdrawal. The measuring probe consists of three optical fibers to which the sensing chemistries are attached, and a thermocouple that measures temperature. The probe is designed to meet in-vivo biocompatibility requirements for a one time use of up to 72 h. The components that are in contact with the patient's blood are nontoxic, nonhemolytic, nonthrombogenic, and sterilizable. Blood compatibility is enhanced by including covalently bound heparin. The in-vitro accuracy of the system has been tested against commercial blood-gas measurement instruments; comparison with tonometry and blood gas values gave r greater than or equal to 0.98 for all three sensors. The standard error for all sensors was within the College of American Pathologists' accuracy guidelines for measuring blood gas. Instrumental drift was minimal, indicating that system performance characteristics should not be the limiting factor in obtaining clinically useful information for up to 72 h. The response times of the sensors in animal and in vitro studies were less than 2 min, suitable for monitoring physiological changes in blood gas values. PMID- 3113768 TI - Comparison of four procedures for separating apolipoprotein A- and apolipoprotein B-containing lipoproteins in plasma. AB - Because lipoproteins containing apolipoprotein A (ApoA-I + ApoA-II) or apolipoprotein B (ApoB) seem to exert opposite effects as risk factors for coronary heart disease, we decided to determine the separability of these two major plasma lipoproteins by procedures originally designed to separate high density from low- and very-low-density lipoproteins. The presumably ApoB-free lipoproteins isolated from normal plasma by (a) ultracentrifugation at d = 1.063; precipitation with (b) heparin-Mn2+ or (c) phosphotungstate-Mg2+; or (d) immunoprecipitation with antibodies to ApoB were characterized by quantifying cholesterol and apolipoproteins A-I, A-II, B, C-II, C-III, D, E, F, and Lp(a). ApoA- and ApoB-containing lipoproteins were completely separated only by immunoprecipitation with antibodies to ApoB. The ApoB-containing lipoproteins isolated by other procedures always contained 4% to 20% of total plasma ApoA-I and differed substantially from one another with respect to the content of some of the minor apolipoproteins. Measuring apolipoproteins was more reliable than measuring cholesterol for monitoring this separation and for expressing the concentrations of ApoA- and ApoB-containing lipoproteins. PMID- 3113767 TI - Application of novel chromium dioxide magnetic particles to immunoassay development. AB - We have used chromium dioxide magnetic particles as the solid support in developing a series of immunological tests. The high surface area (greater than 40 m2/g) available on the magnetic particles and their easy dispersion throughout a solution allow for rapid and complete capture of the target antigen. The magnetic responsiveness of the particles allows for rapid, high-efficiency washing to reduce nonspecific binding, which often limits the sensitivity of serological assays. These features form the basis of extremely rapid and flexible assays for several hormones and markers of cancer and infectious disease. Most of the assays involve monoclonal antibodies. Here we describe specific performance characteristics for thyroxin, follitropin, creatine kinase isoenzyme MB, and antibody to human immunodeficiency virus (HIV). All of the assays are performed in less than 90 min, many in 30 to 45 min. The technology is highly flexible and is suitable for a variety of formats, from manual to fully automated. PMID- 3113769 TI - Two-monoclonal-antibody "sandwich"-type assay of human lutropin, with no cross reaction with choriogonadotropin. AB - We have developed a sensitive, specific, noncompetitive sandwich-type assay for human lutropin (hLH). Two monoclonal antibodies are used, and there is no cross reaction with human choriogonadotropin (hCG) or human follitropin (hFSH), and little or none with human thyrotropin (hTSH). There also is no reaction with the free beta chains of hLH and hCG. The detection limit is less than 0.5 int. units of hLH per liter of serum, and the dose-response curve is linear between 0 and 10 int. units/L. The intra-assay CV averaged 5.4% at low doses of hLH; the interassay CV averaged 12.5%. PMID- 3113771 TI - Follitropin and lutropin simultaneously measured in urine with a commercial radioimmunoassay kit. PMID- 3113770 TI - Measurement of glycated protein by a rapid and specific method for absolute quantification of lysine-bound glucose. AB - We modified the liquid-chromatographic assay of Schleicher and Wieland (J Clin Chem Clin Biochem 1981; 19:81-7) for measuring lysine-bound glucose in serum proteins, increasing its performance and practicality. After precipitating serum proteins from 10- to 50-microL samples with ethanol (700 mL/L) and hydrolyzing these in 6 mol/L HCl, we inject 20 microL of the diluted hydrolysate directly into the chromatograph, which consists of an acid-resistant C18 precolumn combined with a high-resolution C18 main column. The eluent is 3.5 mmol/L H3PO4 solution containing 30 mL of acetonitrile per liter. These modifications increase sensitivity, provide excellent resolution and longevity of stationary phases, shorten assay times to 15 to 20 min, and are suited for automation. The assay is highly sensitive and highly specific, quantifying nanomoles of lysine-bound glucose per milligram of protein. A precision (CV) of 5.1% is achievable at physiological and supra-physiological glucose concentrations, and analytical recovery is 99%. This inexpensive method has been applied to serum albumin, bulk serum proteins, and preparations of low-density lipoproteins and immunoglobulins. PMID- 3113772 TI - Purification and characterization of glutathione S-transferases in human kidney. AB - Four glutathione S-transferase (GST, EC 2.5.1.18) forms were purified from human kidney by S-hexylglutathione affinity chromatography followed by chromatofocusing using a fast protein liquid chromatography system. These forms were demonstrated to be identical with GSTs I, II, IV, V(pi) in human liver previously characterized by us, by SDS-polyacrylamide slab gel electrophoresis, two dimensional gel electrophoresis and double immunodiffusion. GST III (mu) was not detected in any of 5 specimens examined. GST-pi was a major form in the kidney. The activity was 30-40% of the total activity in kidney cytosol and the protein amount was approximately 140 micrograms/g of tissue; 0.27% of the total cytosol protein amount. In many organs including the placenta, GST-pi is present at levels similar to that in the kidney but low in the liver (34 micrograms/g). PMID- 3113773 TI - Estimation and characterization of glycosylated carbonic anhydrase I in erythrocytes from patients with diabetes mellitus. AB - Glycosylated form of carbonic anhydrase isozyme I was found in human erythrocytes. The percent of glycosylated enzyme of the total erythrocyte carbonic anhydrase I of patients with diabetes mellitus was significantly higher than that from normal controls. Characterization of the glycosylated carbonic anhydrase I was studied using an enzyme purified from diabetic patients. The glycosylated enzyme showed a slightly acidic isoelectric point in comparison with that of a nonglycosylated enzyme. The specific activity of the glycosylated enzyme was approximately 40% of that of the normal enzyme, and the immunological activity decreased to 52% of that of the normal enzyme. Estimation of carbohydrates which may form a ketoamine linkage with the enzyme was studied using [3H]-labelled glycosylated enzyme synthesized by incubation of the enzyme with [3H]-D-glucose in vitro, and it was found that one mol of glucose binds to one mol of enzyme. Exposure of red cells to a higher concentration of glucose in diabetics brought about glycosylation of carbonic anhydrase, which is associated with its low activity enzymatically and immunologically. PMID- 3113774 TI - Immunoglobulin light-chain immunoblots of urine proteins from patients with tubular and Bence-Jones proteinuria. AB - Immunoglobulin excretion by patients with monoclonal gammopathies and tubular proteinuria has been analysed by agarose gel isoelectricfocussing of untreated urine and immunoblotting. About three-quarters of the Bence-Jones proteins detected occurred as multiple bands on isoelectricfocussing; in about half of these cases the multiple forms were due to polymerisation or fragmentation of the light chains. In specimens with tubular proteinuria, a characteristic light chain pattern of three broad bands covering the pI ranges 7.1-7.3, 7.8-8.0 and 8.3-8.5 was found. This pattern also occurred in 53% of specimens with Bence-Jones proteinuria and was identical to that found in concentrated normal urine. Intact monoclonal immunoglobulin usually appeared as three or more evenly spaced bands of similar intensity whereas polyclonal intact immunoglobulins produced diffuse staining from pI 5.0-8.5. A scheme for the qualitative analysis of urinary immunoglobulin excretion using this technique has been developed. PMID- 3113775 TI - Relationships between the characteristics of endogenous luteinizing hormone surge and the degree of ovarian hyperstimulation during superovulation induction in women. AB - Ovarian hyperstimulation was induced in 17 normally cycling women undergoing in vitro fertilization (IVF) and embryo transfer with clomiphene (9 cycles), clomiphene followed by pulsatile hMG (12 cycles) or clomiphene followed by pulsatile FSH (11 cycles). Hyperstimulation was greater with the combined treatments than with clomiphene alone. In all 32 cycles an endogenous LH surge occurred. The peak values and the duration of the LH surge showed significant negative correlations with the plasma oestradiol levels, the number of the follicles and the total follicular fluid volume aspirated at laparoscopy. We suggest that during superovulation induction for IVF, the endogenous LH surge is attenuated by factors which are related to the degree of ovarian hyperstimulation. PMID- 3113776 TI - Genetic factors in Graves' ophthalmopathy. AB - We investigated the distribution of HLA and immunoglobulin G heavy chain markers (Gm) in 117 patients with Graves' disease, 62 with ophthalmopathy and 55 without. With Graves' disease per se, there is a closer association with HLA-DR3 than with B8. The opposite was true for Graves' patients with ophthalmopathy (odds ratio for ophthalmopathy associated with B8 was 12.4 and with DR3 was 7.7, both with P less than 0.0005). HLA-DR7 interacts with B8 in modifying the risk for eye disease; using the phenotype B8- DR7- as reference, the odds ratios were 16.7 for B8+ DR7+, 8.7 for B8+ DR7- and 0.26 for B8- DR7+. Thus, DR7 enhanced the risk for ophthalmopathy in the presence of B8+ but had a protective influence in its absence. Although Gm showed no association with eye disease, it modified the risk for ophthalmopathy associated with HLA-B8; the odds ratios were 20.9 for B8+ Gmfb homozygozity (fb+), 15.3 for B8+ fb- and 1.7 for B8- fb+ (B8- fb- = 1.00). We conclude that the genetic factors contributing to Graves' ophthalmopathy are different from those related to liability for Graves' hyperthyroidism. PMID- 3113777 TI - Testicular follicle stimulating hormone receptors and effectiveness of human menopausal gonadotrophin-human chorionic gonadotrophin treatment in infertile men. AB - In order to investigate the relationship between testicular FSH receptors and the effectiveness of hMG-hCG treatment in idiopathic male infertility, 36 infertile men were examined. None of the 13 patients without detectable testicular high affinity FSH receptors showed any increase in motile sperm count after the hMG hCG treatment, whereas 11 of the 23 patients with FSH receptors responded to the treatment. In patients with FSH receptors, patients with a middle or high Johnsen's score count responded more than those with a low score count did. From the above results, it seems that both the presence or absence of testicular FSH receptors and the histological appearance of spermatogenesis predict responsiveness to hMG-hCG treatment in infertile men. PMID- 3113778 TI - Interaction of thyrotrophin releasing hormone and the enkephalin analogue DAMME on pituitary hormone secretion. AB - Because TRH counteracts the inhibitory effect of opiate peptides on LH secretion in cultured cells from normal pituitaries, six normal postmenopausal women were studied to determine whether TRH interacts in vivo with opioid peptides in the regulation of pituitary hormone secretion. At two different times a constant 3 h infusion of either saline or TRH (5 micrograms/min) was initiated. At 60 min a 250 micrograms bolus of the opiate agonist peptide D-Ala2-MePhe4-met-enkephalin-0 ol (DAMME) was injected in one of the two saline and TRH infusion tests. The four treatments, i.e. saline infusion alone, saline infusion with a DAMME bolus, TRH infusion alone; and TRH infusion with DAMME bolus were given at random with an interval of at least 7 d. Blood samples were taken every 15 min during the 3 h study. DAMME induced a significant fall (P less than 0.05) in serum LH (from 35 +/- 8.5 to 18.3 +/- 5.1 mIU/ml) (mean +/- SEM) without significantly affecting FSH levels (from 29 +/- 11.2 to 26.9 +/- 12.4 mIU/ml). These changes were not antagonized by the continuous infusion of TRH. PRL had a monophasic response pattern to continuous isolated TRH infusion; the basal levels increased from 4.2 +/- 1.2 to 24.5 +/- 6.8 ng/ml at 30 min and then slowly decreased with a plateau from 90 min until the end of the study. DAMME administration at 60 min induced a significant second peak of PRL secretion (44 +/- 6.5 ng/ml) 30 min later (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113779 TI - Continuous infusion of growth hormone releasing hormone does not alter the growth hormone response to different stress stimuli. AB - Continuous infusion of GHRH, as well as a bolus injection of GHRH, specifically stimulates the release of GH by the anterior pituitary. However, repetitive bolus injections of GHRH result in diminished responses of GH, while a constant infusion of GHRH cannot maintain high serum GH levels. To investigate whether different GH-releasing stimuli are able further to challenge the somatotroph being exposed to continuous infusion of GHRH, we determined the GH response to insulin-induced hypoglycaemia and bicycle exercise. Six normal volunteers received a bolus of 50 micrograms GHRH or vehicle followed by a continuous infusions of GHRH 1-29 amide (1 microgram/kg/h) or vehicle for 2.5 h. GHRH bolus and infusion resulted in elevated GH levels, but GH levels fell to values not significantly different from baseline levels after 150 min, GH plasma levels rose again, however, in response to insulin hypoglycaemia and bicycle exercise after both GHRH or vehicle infusion. Thus, the somatotroph's responsiveness to GHRH remains intact to respond to stress stimuli after continuous GHRH infusion. PMID- 3113781 TI - Dopamine, the kidney and essential hypertension studies with gludopa. AB - The formation and action of intrarenal dopamine is reviewed, as also is the evidence for the use of gamma-L-glutamyl-L-dopa as a relatively renally specific dopaminergic pro-drug. 'Salt sensitive' patients with essential hypertension may have a fault in the renal mobilisation of dopamine by sodium chloride. This failure of sodium to dopamine coupling may be particularly prevalent in the Negro race. PMID- 3113780 TI - The effect of transdermal oestrogen on bone, calcium-regulating hormones and liver in postmenopausal women. AB - Transdermal oestradiol, 100 micrograms/d, was used to treat 11 women suffering from postmenopausal symptoms. After 3 weeks therapy there was a significant rise in the plasma oestradiol into the premenopausal range and a significant fall in plasma FSH level and symptom score. Bone resorption, assessed by urinary excretion of calcium and hydroxyproline, decreased significantly while plasma alkaline phosphatase activity remained constant. There was a significant fall in plasma calcium and phosphate but the plasma concentrations of PTH, calcitonin and calcitriol and the urinary excretion of cAMP were unchanged. Plasma levels of vitamin D binding protein, albumin and globulin were unaltered, and blood pressure did not rise. These effects were similar to those found in postmenopausal women with oral ethinyloestradiol, 30 micrograms/d, (Selby et al., 1985), apart from those on plasma vitamin D binding protein, total calcitriol, albumin, globulin, tubular reabsorption of phosphate and blood pressure, changes which probably arise from a direct action of oral oestrogen on the liver. PMID- 3113782 TI - Postaxial polydactyly in association with neurofibromatosis. AB - Von Recklinghausen neurofibromatosis may present many skeletal abnormalities as common features. We describe a family with postaxial polydactyly and neurofibromatosis, an association which has not been previously reported. The special characteristics of postaxial polydactyly of this family were its bilateral and symmetrical appearance, its limitation only to males, simultaneous presence of types A and B in the same patient, and its occurrence in both hands and feet. Postaxial polydactyly type A appeared only in the affected neurofibromatotic members of this family. PMID- 3113783 TI - Oral administration of erythrocyte membrane antigen does not suppress anti-Rh(D) antibody responses in humans. AB - The effects of prior oral administration of erythrocyte membrane preparations (Oral Rh antigen) on the serum anti-Rh(D) antibody response has been evaluated in non-sensitized Rh(D)-negative male volunteers, and in female volunteers sensitized previously by Rh(D)-positive fetal blood during pregnancy. Sixty-one percent (11/18) of males who received oral Rh antigen (either D-positive or D negative) before intravenous challenge with Rh(D)-positive cells produced detectable antibodies; of these 11, six received oral Rh(D)-negative antigen and five received oral Rh(D)-positive antigen. Seventy-two percent (13/18) of control males, who had received no prior oral Rh antigen, produced antibodies following challenge with Rh(D)-positive cells. Three out of six pre-sensitized females who received oral D-positive or D-negative Rh antigen for 4 weeks, but without intravenous challenge, increased their anti-Rh(D) antibody levels which peaked after 11-18 weeks: two had received Rh(D)-positive antigen, and one Rh(D) negative antigen. These data indicate that administration of oral Rh antigen before parenteral immunization does not significantly suppress the anti-Rh(D) antibody response. Indeed, oral administration of either Rh(D)-positive or Rh(D) negative antigen can boost systemic antibody in pre-sensitized females. These results do not support the rationale of treating Rh-sensitized pregnant women with oral Rh antigen. PMID- 3113784 TI - Recombinant gamma interferon is a potent adjuvant for a malaria vaccine in mice. AB - Mice were protected against lethal Plasmodium yoelii malaria by vaccination with a Triton X-100 lysate of whole parasitized erythrocytes. For full effectiveness this vaccine required an adjuvant, and we have found that recombinant gamma interferon has strong adjuvanticity in this model when given either intraperitoneally or subcutaneously. Specific immune responses that were enhanced included antibody, T cell help, and delayed hypersensitivity. PMID- 3113785 TI - Transport defect of IgM into luminal space in selective IgA deficiency. AB - This study explored the pathogenesis of a transport defect of IgM into the lumen in a patient with selective IgA deficiency. In addition to the absence of IgM in the saliva, no IgM was localized on the luminal surface of colonic mucosa from the patient despite the presence of J chain-positive IgM cells. On tissue sections, IgM cells did not bind secretory component. The serum IgM also showed a negligible capacity to bind secretory component in vitro. Such abnormalities of IgM molecules as stated above seem to be clinicopathologically linked with IgA deficiency or its associated Sjogren's syndrome. PMID- 3113786 TI - Inhibition of spontaneous proliferation of human leukemic B cells from patients with chronic lymphocytic leukemia by anti-mu antibodies. AB - In a monoclonal system, F(ab')2 fragments of rabbit anti-mu antibody (anti-mu) were found to inhibit the proliferation and differentiation of highly purified E rosette-negative largely leukemic B cells from two patients with chronic lymphocytic leukemia (CLL). Leukemic B cells from these two patients, in contrast with the majority of patients with CLL, exhibited high spontaneous proliferation in culture medium alone. This spontaneous proliferation was significantly inhibited by moderate concentrations of anti-mu (10-50 micrograms/ml). In contrast, lower concentrations of anti-mu (0.6-1.2 micrograms/ml) induced proliferation of leukemic B cells. Conditioned media (CM), derived by stimulation of human peripheral blood mononuclear leukocytes with phytohemagglutinin, induced significant proliferation of these leukemic B cells. This induced proliferation at optimal CM concentrations was inhibited by anti-mu. However, at high CM concentrations, which did not cause significant proliferation, synergism between CM and anti-mu in inducing proliferation was observed. Stimulation of spontaneously proliferating leukemic B cells with CM resulted in differentiation into cells synthesizing and secreting immunoglobulin M (IgM) but not IgG. This IgM production was also inhibited by anti-mu. PMID- 3113787 TI - Lupus anti-ribosomal P peptide antibodies show limited heterogeneity and are predominantly of the IgG1 and IgG2 subclasses. AB - A 22-amino acid synthetic peptide (P peptide) containing the conserved, shared autoantigenic determinants of the ribosomal P proteins was conjugated to rabbit serum albumin and used to analyze anti-P heterogeneity in 17 lupus sera. Anti-P peptide antibodies demonstrated moderate restriction in isotype (IgM and IgG, but not IgA), subclass (predominantly IgG1 and IgG2), light chain type (predominantly kappa) and spectrotype. In one serum, almost exclusive use of IgG2 and the kappa light chain was observed. These findings indicate that there is a nonrandom selection of heavy and light chain constant region genes as well as limited variable region diversity in the anti-P peptide response. PMID- 3113788 TI - Induction of interferon-gamma in human leukocyte cultures stimulated by Zn2+. AB - Our studies have confirmed previous reports that Zn2+ has a mitogenic effect on human lymphocytes. Furthermore, we have tested the ability of Zn2+ to induce interferon production in human leukocyte cultures. Peripheral blood mononuclear cells were stimulated with ZnCl2 at different concentrations. Interferon was detected in the supernatants of cultures stimulated with concentrations ranging from 5 X 10(-4) to 5 X 10(-5) M. Interferon was produced only in the presence of accessory cells. The type of interferon induced by Zn2+ was interferon-gamma, as proven by the use of specific antisera. PMID- 3113789 TI - A study of Mycobacterium tuberculosis antigen and antibody in cerebrospinal fluid and blood in tuberculous meningitis. AB - Radioimmunoassay (RIA) techniques have been evaluated to detect specific tubercular antigen (TB Ag) and antitubercular antibody (TB Ab) in CSF and serum of patients with tuberculous meningitis (TBM). A solid-phase RIA using H37RV sonicate antigen of Mycobacterium tuberculosis, anti-BCG antibody, and staphylococcal protein A was standardized. TB Ag and TB Ab levels were noted to be significantly elevated in cerebrospinal fluid (CSF) as well in circulating immune complexes (CIC) isolated from serum samples of TBM patients as compared to control group (P less than 0.01). Detectability of disease by demonstrating elevated TB Ag and/or TB Ab levels in either CSF or CIC or both was 95%. There was no correlation between individual levels of TB Ag and TB Ab in CSF and in circulation. A follow-up study in patient over a period of 4-12 weeks revealed that TB antigen and/or TB Ab persisted in the majority of the cases for several weeks despite chemotherapy. PMID- 3113790 TI - Resistance to experimental autoimmune thyroiditis induced by physiologic manipulation of thyroglobulin level. AB - The role of circulatory mouse thyroglobulin (MTg) level in activating mechanisms suppressive to induction of experimental autoimmune thyroiditis (EAT) was studied by two regimens to strengthen normal maintenance of self-tolerance in genetically susceptible mice. One was to administer graded doses of exogenous MTg either 7 days apart or daily for 10 days and then challenge the animals with MTg + LPS. The other was to infuse TSH via an osmotic pump for 7 days. The steady TSH infusion for 7 days resulted in an increase in MTg level peaking on Day 3. Such kinetics of MTg concentration in response to TSH coincided with enhanced resistance to EAT induction. After an initial rapid clearance rate of t1/2 of 3 hr, tolerogenic doses of exogenous MTg sustained similar levels for 2-3 days. In contrast, subtolerogenic doses declined to baseline levels in 2 days or less. Clearance can be best explained by a two-compartment model for distribution with an initial alpha phase (t1/2 about 3 hr), followed by a beta phase (t1/2 about 10 hr). We conclude that, for the prevention of EAT induction in the presence of potent adjuvants (CFA or LPS), a threshold, but above baseline, level of either exogenous or endogenous MTg, represented by the beta phase, is required for a critical period (greater than 2-3 days) to activate suppressor mechanisms over and above homeostatic regulation. Whether MTg concentration raised by TSH (TRH) administration activates suppressor T cells as observed after the injection of a tolerogenic dose of MTg remains to be determined. PMID- 3113791 TI - Deposition of fibrin-stabilizing factor (F XIIIA and S), fibrinogen-related antigens, fibrinogen degradation products (FDPd and FDPe) and antihemolytic factor (F VIII) in renal disease: analysis of 161 cases by immunofluorescence microscopy. AB - To see whether or not the fibrin-stabilizing factor is involved in the pathogenesis of renal damage, we analyzed by IF the glomerular deposition of factor XIII (subunits A and S) in 161 patients with various renal diseases. In 4 out of 5 cases of thrombotic microangiopathy (80%), F XIII deposits were found in a continuous subendothelial pattern, in association with deposition of fibrinogen and FDP, suggesting the occurrence of intraglomerular coagulation. In 22 out of 45 patients with membranous GN (idiopathic or SLE-associated), F XIII deposits were found along the capillary walls in a subepithelial location. These findings were not correlated with the presence of particular histological or clinical features, nor with IF positive for fibrinogen, FDP and factor VIII, suggesting alternative pathways of fibrin formation or local collagen synthesis. Finally, in proliferative GN, either idiopathic (acute post-infectious and membranoproliferative) or systemic (SLE and vasculitis), as in other glomerular and non-glomerular diseases, the presence of F XIII deposits was negligible, even in cases positive for fibrinogen, FDP and factor VIII. PMID- 3113792 TI - Efficacy and tolerance of tocainide during long-term treatment of malignant ventricular arrhythmias. AB - A group of 51 patients with malignant ventricular arrhythmias refractory to standard oral antiarrhythmic agents were treated with oral tocainide. Antiarrhythmic efficacy was defined as total abolition of occurrences of ventricular tachycardia (VT) or ventricular fibrillation (VF) as assessed by hospital admissions for arrhythmias and the occurrence of sudden cardiac death (SCD). Of the 51 patients, 32 (63%) initially tolerated tocainide and were discharged from the hospital. Of the 19 patients not initially responding to tocainide, 6 (12%) had arrhythmia recurrence and 13 (25%) developed intolerable central nervous system or gastrointestinal side effects. Of these 19 short-term nonresponders, 8 (42%) patients suffered SCD over an average follow-up of 24 months (annual SCD rate of 21%). Two patients suffered SCD during the first week of tocainide therapy. Discounting the 2 patients with SCD on tocainide therapy, 6 of 17 (35%) patients initially withdrawn from tocainide suffered SCD (annual SCD rate of 18%). Twenty-four of the 32 short-term responders did not have arrhythmia recurrence over a mean follow-up of 38 months resulting in an overall long-term efficacy of 47% (24/51). Over an average follow-up of 38 months for these 24 short-term responders, 12 patients expired from nonarrhythmic causes, 3 patients were withdrawn for non-drug-related causes, and 9 patients remain on tocainide therapy. Of the 8 long-term nonresponders, 3 patients had arrhythmia recurrence and died suddenly while 5 patients developed intolerable side effects. The annual SCD rate in short-term responders was 3%. Eighteen of the 51 patients (35%) were withdrawn from the study because of adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113793 TI - Hemodynamic effects of transdermal nitroglycerin in subjects with angina and without congestive heart failure: comparison between never treated and chronically treated subjects. AB - Two groups of patients with angina were studied: Group A, 9 patients not treated previously with nitroderivatives; Group B, 8 patients, treated with transdermally administered nitroderivatives for at least 4 weeks. Hemodynamic parameters did not differ significantly in these groups under baseline conditions; only systolic blood pressure was higher in Group B (165 +/- 16 mmHg) than in Group A (144 +/- 15 mmHg). Hemodynamic modifications produced by administering nitroglycerin transdermally in these patient groups were evaluated 100 min after the transdermal application. In Group A significant reduction of systolic (144 +/- 15 to 126 +/- 18 mmHg, p less than 0.01) and diastolic blood pressure (83.36 +/- 70.1 +/- 13 mmHg, p less than 0.05), mean right atrial pressure (4.8 +/- 2.1 to 3 +/- 1.7 mmHg, p less than 0.005), mean pulmonary arterial pressure (18.6 +/- 2.6 to 16.7 +/- 2.8 mmHg, p less than 0.01), and significant increase of heart rate (72 +/- 10 to 83.5 +/- 12.4 beats/min, p less than 0.005) were noted. In Group B we noted only a significant reduction in systolic (170 +/- 25 to 150.5 +/- 16 mmHg, p less than 0.05) and diastolic blood pressure (88.7 +/- 15.5 to 77.5 +/- 9.2 mmHg, p less than 0.05) without other modifications. We conclude that prolonged treatment with adequate doses of transdermal nitroglycerin causes the hemodynamic effects of the medication to dissipate from the venous tone and significant arteriodilative effect to persist. PMID- 3113794 TI - Attenuation of nitroglycerin-induced coronary hyperemic blood flow in patients with left anterior descending coronary collaterals. AB - Although intracoronary nitroglycerin (NTG) is frequently administered to patients having occluded coronary arteries undergoing invasive procedures such as percutaneous transluminal coronary angioplasty or thrombolysis, the extent of NTG induced augmentation of myocardial blood flow in patients with collaterally filled occluded arteries is incompletely understood. To examine NTG-induced increases in coronary blood flow in patients with occluded left anterior descending coronary arteries (LAD), coronary and systemic hemodynamics were measured during bolus administration of NTG into the left coronary artery in 10 patients with normal LAD (Group 1), 11 patients with greater than 70% and less than 100% narrowing of the LAD (Group 2), and 10 patients who had total occlusion of the LAD with angiographic collateral filling and anterior ventricular wall motion abnormalities (Group 3). NTG increased anterior regional great vein flow (thermodilution) from 72 +/- 19 to 140 +/- 60 ml/min (p less than 0.05), 67 +/- 27 to 108 +/- 66 ml/min (p less than 0.05), and 59 +/- 27 to 74 +/- 36 ml/min (p = NS vs. control, p less than 0.05 vs. peak flow for Group 1) with relative increases from control of 91 +/- 41%, 56 +/- 34%, and 25 +/- 22% for the three groups, respectively. The percent change for Group 3 was significantly lower than both Groups 1 (p less than 0.01) and 2 (p less than 0.05). These data indicate that myocardial hyperemic blood flow responses to intracoronary NTG are markedly attenuated in patients with occluded but collaterally supplied vessels. During invasive procedures in these patients, although significantly attenuated, intracoronary NTG may potentially provide a beneficial effect by augmenting blood flow through collaterals or in adjacent regions. PMID- 3113795 TI - Peptic ulcer--current status. AB - Important problems currently under study or requiring investigation for better understanding of the pathophysiology and management are reviewed under three major categories: acute peptic erosions and ulcers, gastric ulcer, and duodenal ulcer. In patients with acute erosions and ulcers, we need to identify patients at risk for major bleeds, to prevent lesions induced by anti-inflammatory, non steroidal drugs, as well as bleeding from stress ulcers, and to perfect and establish the efficacy of endoscopic methods for coagulation of bleeding ulcers. In patients with gastric ulcers, we need to establish the relative importance of gastric acidity and mucosal resistance to ulcerogenesis, to determine factors that influence healing rates, and to uncover the factors responsible for recurrence. In duodenal ulcer patients, we need to determine the relative importance of post-prandial versus interdigestive secretion, the role of pepsin, and the importance of local defense mechanisms such as bicarbonate and mucus secretion, cellular defense, and blood flow. The mechanisms of failure to heal during treatment need attention. The relation of symptoms and clinical course to healing of ulcer craters should continue to be considered, as well as the long term course of ulcer disease. The consequences of long-term suppression of acid secretion are a potential hazard, and, finally, the prevention of recurrence remains the major clinical problem in duodenal ulcer. PMID- 3113796 TI - Prostaglandins and related products profiled by GC/MS with negative-ion chemical ionization detection. AB - A simple procedure is described which permits the quantification of 6 primary prostaglandins and their 15-keto and 15-keto-13,14-dihydro metabolites. Analysis is made through high-resolution gas chromatography with detection by mass spectrometry in the negative ion chemical ionisation mode. The method is capable of detecting these products in normal whole blood. PMID- 3113797 TI - Morphological and physiological effects of a cytoprotective prostaglandin analog (rioprostil) on the rat gastric mucosa. AB - This study was undertaken to investigate the ability of a cytoprotective synthetic primary alcohol PGE1 analog, rioprostil, to protect the rat gastric mucosa against topically applied 40% (v/v) ethanol. Use of an ex vivo gastric chamber model facilitated correlation of changes in dynamic physiological parameters (PD and net cation fluxes) with changes in mucosal structure. We were particularly interested in defining changes in mucosal structure which accompanied topical application of rioprostil and which might explain subsequent resistance to the effects of ethanol. Topical application of rioprostil for 10 min provided concentration-dependent protection against ethanol-induced hemorrhagic erosions. The most effective dose and concentration tested (25 micrograms rioprostil at a concentration of 10 micrograms/ml) completely prevented ethanol-induced lesion formation. Protection was not accompanied by significant preservation of the interfoveolar epithelium against ethanol, but did involve prevention of vasocongestion and limitation of damage to the superficial epithelium. Complete recovery of physiological parameters indicative of gastric mucosal barrier integrity occurred within 20 min. The most effective concentrations of rioprostil produced extensive subepithelial edema and, concurrently, significant increases in net efflux of sodium ions, decreases in mucosal PD, and loss of mucosal folding. PMID- 3113798 TI - Misoprostol attenuates aspirin-induced changes in potential difference and associated damage in canine gastric mucosa. AB - Aspirin induces ulceration, cellular exfoliation, and blood loss associated with decreases in gastric mucosal potential difference (PD). Certain prostaglandins prevent the development of experimental gastric and duodenal ulcers and modify indices related to ulceration. Misoprostol, a synthetic PGE1 derivative with gastric antisecretory and mucosal protective activities, was examined at gastric antisecretory doses in dogs with Heidenhain pouches, to determine its effect on aspirin-associated changes in PD, K+ efflux, blood loss, and cell shedding, as measured by DNA release. These parameters were examined before, during, and up to 4 hours after exposure of the pouches to aspirin. Disruption of the gastric mucosal barrier (GMB) by aspirin was associated with a fall in PD and losses of K+, DNA, and blood into the pouches. Misoprostol inhibited the fall in PD and prevented blood loss over the entire period examined. Cell loss was inhibited only during the recovery period immediately following aspirin. The effect of misoprostol on GMB is consistent with studies in which prostaglandins preserve the GMB and prevent necrotic ulcerations while allowing superficial cell damage. PMID- 3113799 TI - Pepsinogens, pepsins, and peptic ulcer. AB - The role of pepsin in the pathogenesis of peptic ulcer has been the subject of intense study and debate for many years. Two difficulties inherent in distinguishing between the role of acid alone vs acid and pepsin are that a) acid containing gastric juice always contains pepsin, and, b) that hydrogen ion concentration (pH) is a major determinant of the activity of pepsin. However, studies in animal models of peptic ulcer indicate clearly that pepsin, in combination with acid, produces much more severe and more extensive mucosal damage than acid alone. Recent interest in pepsin and its precursor, pepsinogen, has stemmed from the finding that each is remarkably heterogeneous, and that the heterogeneity has a genetic basis. Results of studies using radioimmunoassays specific for the 2 major forms of pepsinogen, pepsinogen I and pepsinogen II, have shown that serum levels of pepsinogen I and pepsinogen II, and the ratio of pepsinogen I to pepsinogen II, can be used as noninvasive probes of gastric mucosal structure and function, indicators of the genetics and heterogeneity of duodenal ulcer, and as markers of increased risk for duodenal ulcer and gastric ulcer. PMID- 3113801 TI - Focus on misoprostol: review of worldwide safety data. AB - Gastrointestinal symptoms have been the most frequently reported adverse experiences in the misoprostol (Cytotec) studies of both patients with peptic ulcer disease, and healthy subjects. There have been relatively few cardiovascular, genito-urinary, or other adverse effects. This is similar to the results of animal studies in which misoprostol had little, if any, effects on cardiovascular, central nervous, and endocrine systems. The predominant activity of misoprostol in the gastrointestinal tract, essential to its ulcer-healing activity, may also account in part for the association of misoprostol with gastrointestinal adverse experiences. Abnormal bowel movements were the most common complaint (9-13%) of patients in pivotal controlled studies. In patients taking misoprostol 200 micrograms four times daily, 7.1% had diarrhea, with less than 1% stopping therapy because of diarrhea. Abdominal pain in these patients was reported in an incidence of 12.8%, was mild, and only rarely resulted in stopping therapy. Other adverse reactions reported in these patients were nausea, headache, and dizziness. In pregnant women, undergoing a legal termination of pregnancy, it has been shown that misoprostol has a greater incidence of uterine bleeding, and partial or complete expulsion of uterine contents, than placebo. Misoprostol (Cytotec) has received government approval for marketing in 12 countries, since the first gave its approval in June, 1984. It has been launched in 6 of those markets to date, with an estimated 100,000 patients having taken the drug. No serious adverse experiences attributed to misoprostol have been reported, but mild adverse experiences have occurred. Those most frequently reported were gastrointestinal in nature, and included diarrhea, abdominal pain, and nausea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113800 TI - Efficacy of prostanoids in the treatment of gastric ulcer. AB - Prostanoids decrease gastric acid secretion and exert cytoprotective properties. The effect of several synthetic prostanoids on gastric ulcer healing was evaluated. The first trials were performed on a small number of patients with PGE2 analogs and their results were inconclusive. Two huge multicenter trials tested the efficacy of misoprostol, a synthetic PGE1 analog, in comparison to placebo and cimetidine. In the placebo-controlled trial, following 8 weeks of therapy, misoprostol 100 micrograms q.i.d was significantly better than placebo. In the cimetidine controlled trial, 2 doses of misoprostol were tested, 50 micrograms and 200 micrograms q.i.d. Ulcer healing rates following 4 weeks were 39%, 51%, and 58% in the misoprostol 50 micrograms, 200 micrograms, and cimetidine treatment groups, respectively. There was no statistically significant difference in the healing rates at 4 weeks between the misoprostol 200 micrograms and cimetidine 300 mg q.i.d groups (P = 0.16). The healing rate with the misoprostol 200 micrograms dose was significantly better than with the 50 micrograms dose (P = 0.008). Cimetidine 300 mg relieved global pain significantly better than misoprostol 200 micrograms at 2 weeks (P = 0.047) but not at 4 weeks. The 200 micrograms dose of misoprostol relieved pain significantly better than the 50 micrograms dose at 4 weeks (P = 0.019), but not at 2 weeks. All 3 treatments were well tolerated. Severe adverse events were rare. The efficacy of enprostil, another PGE2 analog, on gastric ulcer healing was also found to be better than placebo and not significantly different from ranitidine. The synthetic prostanoids, misoprostol and enprostil, appear to be safe and effective in the treatment of gastric ulcer. PMID- 3113802 TI - Other causes of GI mucosal injury: upper intestinal content. AB - Factors in upper intestinal content that can produce acute injury to the gastric mucosa include lysolecithin and the bile acids. Both damage the gastric mucosal barrier by increasing mucosal permeability. The secondary and deconjugated bile acids are more toxic in this regard than are the primary or conjugated ones. The extent of injury is highly pH-dependent. Although the bile acids do not affect the gel properties of gastric mucus, they do produce significant inhibition of carbonic anhydrase activity and gastric bicarbonate secretion. In concert with other topical damaging agents, bile acids increase mucosal blood flow. However, gross mucosal lesions are rarely observed under these circumstances. Chronic exposure of acid-peptic-secreting mucosa to upper intestinal content results in the development of a severe atrophic gastritis within 6 months. The ability of atrophic mucosa to maintain an intraluminal pH gradient is impaired, and it ulcerates with great regularity when exposed to a highly acid environment. Clinically, excessive enterogastric reflux has been implicated in the pathogenesis of both benign gastric ulcer and the post-gastrectomy syndrome of alkaline reflux gastritis. The evidence to support this view for both disease entities is reviewed. PMID- 3113803 TI - Prevention of medical complications in orthopedic trauma. AB - In severely traumatized patients, morbidity and mortality can be reduced by early management of the skeletal injuries. However, prevention of the complications of shock, pulmonary distress syndrome, embolic phenomena, blood disorders, and immunologic, neuroendocrine, and metabolic problems have a very high priority in overall patient management. PMID- 3113805 TI - Meningococcal conjunctivitis in neonates. AB - Three neonates were admitted with purulent conjunctivitis, and an initial diagnosis of gonococcal ophthalmia was made because gram-negative diplococci were seen on gram stains of conjunctival exudates. Meningococci were grown from eye exudates of all three infants and from the blood of one. Since Neisseria species other than gonococci can sometimes cause neonatal ophthalmia, an etiologic diagnosis should not be made until microbiologic identification is complete. Before the results of definitive bacteriologic studies are known, care should be taken in discussing the cause of the infection with family members and in planning their medical management. Since systemic infections may occur in some infants with ophthalmia due to Neisseria species, blood and spinal fluid in addition to eye exudate cultures may be indicated, and patients should be managed with parenteral antibiotics. PMID- 3113804 TI - A multicenter, randomized, single-blind evaluation of cefuroxime axetil and phenoxymethyl penicillin in the treatment of streptococcal pharyngitis. AB - Ninety-three children from four pediatric practices, with clinical and bacteriologic evidence of acute Group A beta-hemolytic streptococcal pharyngitis (GABHS) randomly received cefuroxime axetil (60 cases) or phenoxymethyl penicillin (33 cases). Cefuroxime axetil was given twice daily (125 mg). Phenoxymethyl penicillin was given three times daily (250 mg). The treatment groups were similar. Throat cultures were routine 2 to 7 days after the start of therapy and 2 days and 14 days after the end of therapy. The bacterial cure rates were 85 percent (51/60) for cefuroxime axetil, and 88 percent (29/33) for phenoxymethyl penicillin treated patients. Clinical results were comparable in both treatment groups. It was concluded that cefuroxime axetil given twice daily is as effective as phenoxymethyl penicillin given three times daily in producing bacteriologic eradication and clinical symptomatic improvement in children with GABHS. PMID- 3113806 TI - Variable glyceryl dinitrate formation as a function of route of nitroglycerin administration. AB - Plasma concentrations of 1,2- and 1,3-glyceryl dinitrates were measured in each of four healthy volunteers who received intravenous infusions (10, 20, and 40 micrograms/min), topical ointment (20 mg/200 cm2), and oral solution (6.5 mg) doses of nitroglycerin and from two subjects who received sublingual (0.4 mg) nitroglycerin. The ratio of 1,2-glyceryl dinitrate to 1,3-glyceryl dinitrate (dinitrate ratio) was determined for each subject after each dose and was found to vary with route of administration. Dinitrate ratios were 7.36, 4.60, 3.86, and 1.99 for intravenous, sublingual, topical, and oral doses, respectively. Nonspecific metabolism of nitroglycerin would result in twice as much of the 1,2 dinitrate as the 1,3-dinitrate (i.e., a dinitrate ratio of 2.0, such as that produced after oral administration). A high ratio (e.g., after intravenous administration) indicates that the metabolism was more specific. These results indicate that metabolite formation depends on route of administration, implying different metabolic specificity of enzymes in the gut, liver, skin, sublingual mucosa, and blood vessels. PMID- 3113807 TI - Use of osmium etching procedures for studying the ultrastructure of isolated rat islets of Langerhans. AB - Variants of the osmium etching procedure, described by Tanaka et al. for the demonstration of the structure of organelles by scanning electron microscopy, have been utilized in studies of isolated rat islets of Langerhans. Use of a preliminary glutaraldehyde fixation followed by the osmium etching procedure originally described, allowed effective removal of the cytoplasmic ground substance, as demonstrated by transmission electron microscopy. High resolution scanning electron microscopy of similar preparations permitted studies of the interaction of cytoskeletal elements with individual organelles. In particular, direct interactions of insulin storage granules with cytoskeletal elements were clearly evident. PMID- 3113808 TI - Electron arc therapy: beam data requirements and treatment planning. AB - In electron arc therapy a long narrow beam defined by a secondary collimator is used to sweep across the treatment area of the patient. Central axis percentage depth doses and off-axis ratios measured with such a collimator show variations with the source-to-surface distance (SSD). Errors may be introduced into isodose distributions calculated with the effective SSD method when beam data measured at a fixed SSD are used. A treatment planning algorithm using beam data measured at two SSDs to allow an interpolation and extrapolation procedure to account for SSD variations has been implemented. For calculations in off-axis planes, off-axis ratios normal to the plane of rotation are also required. Results of the calculations were checked with film dosimetry measurements and found to be in good agreement. PMID- 3113809 TI - Striation of the renal pelvis and ureter in bilharziasis. AB - The intravenous urograms of 80 patients aged 16 to 29 (mean 23) with urinary bilharziasis were reviewed to determine the frequency of striation of the renal pelvis and ureter. Another 345 patients aged 16 to 29 (mean 22) with various abdominal and urological symptoms, had intravenous urography during the same period and were used as a reference group. Striation of the upper urinary tract was demonstrated in 21% of the patients with urinary schistosomiasis but in only 3% of the reference group. Striation constitutes an early radiological change in this disease. PMID- 3113810 TI - Physician and ombudsman in long term care. PMID- 3113811 TI - Production of prostanoids by rheumatic synovial cells in vitro: effects of anti inflammatory drugs on arachidonic acid metabolism. AB - To evaluate the role of prostanoids in rheumatoid arthritis the effects of anti inflammatory drugs on prostanoid concentrations and their ratios were studied in a primary culture of adherent synovial cells from patients with rheumatoid arthritis. Cells from rheumatoid synovium have a great capacity for prostanoid production. PGE2 is the main prostanoid but synovial cells are also capable of producing 6-keto-PGF1 alpha and PGF2 alpha. There were also very low TxB2 concentrations in the culture medium after incubation. All nonsteroidal anti inflammatory drugs used (diclofenac, indomethacin and tolfenamic acid) reduced markedly, in concentrations achieved therapeutically (greater than or equal to 0.13 mumol/l), the production of all the prostanoids from endogenous substrate. There were no differences in the efficacity of the drugs. Hydrocortisone was needed for higher concentrations to inhibit PGE2, 6-keto-PGF1 alpha and PGF2 alpha production. TxB2 formation remained almost unaltered. After the drug incubation there were also clear alterations in the ratios between these prostanoids, which may have therapeutic importance. It is suggested that this kind of synovial cell culture can be used for testing the effects and mechanisms of different anti-inflammatory drugs in standardized cell culture conditions. PMID- 3113812 TI - Articular mobility in systemic lupus erythematosus (SLE). AB - The study was prompted by the suggestion that inflammatory polyarthritis and corticosteroids increase articular mobility. Ninety female patients with systemic lupus erythematosus (SLE) of whom 85 had polyarthritis and at least 75 of whom had received corticosteroid therapy were studied and compared to an equal number of carefully matched controls. The difference between the number of hypermobile patients [6 (7%)] and controls [5 (6%)] was not significant. There was also no significant difference when either the pooled mobility scores or the pooled hand scores of the patients and controls were compared. No significant association between articular mobility and either age at onset of disease, duration of disease or corticosteroid therapy was demonstrated. There was a significant association between deformity and duration of disease (p = 0.04) but not with mobility score. We conclude that SLE patients do not have a hypermobile tendency and therefore that neither SLE nor corticosteroids predispose to increased articular mobility. There is also no association between articular mobility and deformity. PMID- 3113813 TI - Antibodies to soluble and insoluble nuclear antigens in systemic diseases. PMID- 3113814 TI - A simple and accurate automated system for continuous long-term metabolic studies during artificial ventilation. AB - Energy expenditure and the amount of metabolised carbohydrate, protein and lipid can be calculated from the O2 consumption, CO2 production and nitrogen excretion using indirect calorimetry. A low-cost automatic system has been developed suitable for short- and long-term measurements during artificial ventilation, in which the gas analysers were calibrated automatically every 10 min and in which the desired variables were calculated and printed every 5 min. O2 and CO2 concentrations of mixed expired and inspiratory gas, the expired minute volume VE, and patient's rectal temperature, were sampled at regular time intervals and a simple programmable calculator with printer was used for the on-line data analysis. Tests on accuracy, stability, reproducibility and feasibility showed this system to be suitable for clinical application. PMID- 3113815 TI - The acute effects of platelet apheresis on peripheral blood lymphocyte subsets. PMID- 3113816 TI - Skin signs in pulmonary disease. AB - We have described many of the cutaneous findings that can be associated with pulmonary disease. Some, such as the vascular reaction patterns, are quite common. Others, particularly those related to the genetic disorders are rather seldom seen. Our intent, however, is to show how recognition of cutaneous markers can assist the internist in caring for their patients with pulmonary disease. PMID- 3113817 TI - Production of monoclonal antibodies recognising N-ethylmaleimide during attempted generation of monoclonal antibodies to human type I procollagen. AB - Mice were immunised for the production of monoclonal antibodies to human procollagen (I) using antigen purified from fibroblast conditioned medium. The procedure for procollagen (I) preparation included the addition of proteinase inhibitors N-ethylmaleimide, phenylmethylsulphonyl fluoride and ethylenediaminetetraacetic acid to prevent damage by proteolytic cleavage. Four of the five monoclonal antibodies subsequently produced were found to recognise the thiol proteinase inhibitor N-ethylmaleimide but not type I procollagen prepared in the absence of N-ethylmaleimide. One of these monoclonal antibodies was examined further and shown to recognise beta-galactosidase after it had been reacted with N-ethylmaleimide. As far as we are aware this is the first time that monoclonal antibodies have been produced which recognise N-ethylmaleimide. Our findings indicate an unexpected reaction between procollagen and N-ethylmaleimide and prompt the suggestion that the use of N-ethylmaleimide in the purification of procollagen and other proteins should be reexamined. PMID- 3113818 TI - Effects of 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) on the synthesis of dentin matrix proteins in the mouse. AB - The drug 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) is known to inhibit the mineralization of bone and dentin. Its mechanism of action, however, has not yet been elucidated. In order to study its effects on dentinogenesis, mice were supplied with either physiological saline or HEBP in a dose of 10 mg P/kg body weight. This dose is known to interfere with the deposition of mineral crystallites in dentin matrix. The animals were then given a combined injection of [3H]-serine and [14C]-proline (or [14C]-glycine) and killed 8-9 days thereafter. The dentin proteins were isolated and fractionated in soluble proteins among which phosphoproteins, CNBr-peptides of collagen and collagen associated phosphoproteins. It was found that HEBP had a strong inhibitory effect on the synthesis of phosphoproteins and to a lesser extent on that of collagen. The inhibition of the formation of these proteins is supposed to be related to the impaired calcification of dentin under the influence of the bisphosphonate. PMID- 3113819 TI - Purification and properties of beta-galactosidase from chicken seminal plasma. AB - 1. beta-Galactosidase (EC 3.2.1.23) from chicken seminal plasma was purified approx. 111-fold to homogeneity. 2. pH optimum of the enzyme ranged from 3.6 to 4.0 and its Km was 0.65 mM with p-nitrophenyl-beta-D-galactoside as substrate. 3. The enzyme was unstable at its optimal activity pH and was activated by Cl- ions. 4. The enzyme had pI value of 4.0. 5. The active enzyme had Mr approx. 100,000 by Sephacryl S-300 chromatography. SDS electrophoresis in the presence of beta mercaptoethanol showed four bands corresponding to Mr of approx. 90,000, 75,000, 65,000 and 13,000. PMID- 3113820 TI - Chicken liver purine nucleoside phosphorylase activity dependency of the redox state of sulfhydryl groups. AB - 1. Double reciprocal plots (1/v vs 1/S) for nucleoside substrates of chicken liver purine nucleoside phosphorylase were non linear at high inosine or deoxyinosine concentrations (greater than 0.1 mM). The appearance of downward curvatures may be correlated with the oxidation of sulfhydryl groups of the enzyme. 2. 5,5'-Dithiobis-(2-nitrobenzoic acid) reacts with four sulfhydryl groups in the native enzyme, but upon denaturation with sodium dodecylsulfate six sulfhydryl groups react with this reagent. 3. Inosine, ribose-1-phosphate, hypoxanthine and orthophosphate partially protect sulfhydryl groups from the reaction with Ellman's reagent. 4. Inhibition of purine nucleoside phosphorylase by p-chloromercuribenzoate and 5,5'-dithiobis-(2-nitrobenzoic acid) follows a second order reaction kinetics. PMID- 3113821 TI - Heterogeneity of hepatic microsomal UDP-glucuronosyltransferases activities: use and comparison of differential inductions in some mammalian species. AB - 1. The co-injection in rats of the inducers 3-methylcholanthrene or phenobarbital and of a protein synthesis inhibitor (cycloheximide) shows that two clusters of hepatic UDP-Glucuronosyltransferases (GT1 and GT2) are under separate genomic expression and differentially regulated. 2. The administration of cycloheximide alone even suggests a distinct turn-over for these two groups of isoenzymes. 3. Indirect evidence for a UDPGT isoform specialized for some structurally-related exogenous substrates, the monoterpenoid alcohols, is brought. Their conjugation exhibits a small deficiency and a marked response to phenobarbital treatment in the Gunn rat and an exclusive inducibility by phenobarbital in the guinea-pig. PMID- 3113822 TI - Plasma levels of cortisol and corticosteroid binding globulin during use of Norplant-2 implants. AB - Plasma levels of cortisol and corticosteroid binding globulin (CBG) were studied during one year in eleven healthy women using NORPLANT-2 implants. NORPLANT-2 implants release approximately 50 ug of levonorgestrel/day. A significant diurnal variation of cortisol levels was found during the study. No significant change in cortisol levels compared to pretreatment levels was found. Levels of CBG showed no diurnal variation, but decreased significantly during use of the implants. This was most probably due to a direct effect of the levonorgestrel, as the levels of estradiol did not change compared to pretreatment levels, except for the values after 6 months that were significantly lower than pretreatment levels. A "free cortisol index" calculated as: level of cortisol/level of CBG, was unchanged during treatment compared to pretreatment levels. It is concluded that although CBG levels were reduced, no significant change in cortisol patterns was seen during use of the implants. PMID- 3113823 TI - ICMR task force study on hormonal contraception. Transfer of levonorgestrel (LNG) administered through different drug delivery systems from the maternal circulation into the newborn infant's circulation via breast milk. AB - The transfer of levonorgestrel (LNG) from the maternal plasma via breast milk to the infant was studied in 38 fully lactating and breast-feeding women at 4-6 weeks postpartum, for a duration of 28 days. These volunteers were provided with LNG contraceptive treatment delivered through three, different routes of drug delivery system: (i) intrauterine devices impregnated with LNG (LNG-IUD); (ii) subdermal implant (Norplant (R)-2); and (iii) minipills (LNG 30 micrograms daily). On the first day after either the LNG-IUD (n = 14 women) or Norplant (R) 2 (n = 14 women) insertion, the maternal blood and breast milk samples were collected at 2, 4 and 8 hourly intervals. This was followed by daily collection of these samples as well as infant's blood from days 2 to 4 and thereafter on days 7, 14 and 28. For infant's blood samples from LNG minipill users (n = 10 women), only a single 4-hour sample was collected on the first day and no samples were collected on days 3 and 4. The rest of the schedule for collection of maternal blood and breast milk as well as infant's blood samples were the same in minipill users as for the other two treatment groups. The study revealed a lower LNG percentage transfer from maternal sera to breast milk--11.8 +/- 2, 7 +/- 2 and 8 +/- 1 and relatively higher percentage LNG transfer from breast milk to infant's sera--75 +/- 17, 68 +/- 20 and 32 +/- 3, in LNG-IUD, Norplant (R)-2 and minipill users, respectively. Therefore, LNG contraceptive steroid is transferred into the infant's circulation, the biological significance of which remains to be established. PMID- 3113824 TI - Contemporary concepts of antigenic variation. PMID- 3113825 TI - Application of a combination of sublingually administered vasodilating drugs for rapid action on pulmonary hypertension in patients with cardiac asthma and with pulmonary oedema. AB - Eight patients with pulmonary oedema and 6 patients with cardiac asthma (primary disease: in 7 patients acute myocardial infarction, in 6--hypertension, in 1- mitral defect) were given sublingually a combination of 0.5 mg nitroglycerin, 10 mg Isodinit (isosorbid dinitrate) and 4 mg Sidnofarm (molsidomine) in powder form. This resulted in a rapid, pronounced and protracted reduction of dyspnoea, pulmonary congestion, respiration rate, and heart rate in the course of a four hour observation rate, in more than 80% of cases. In patients with high blood pressure it dropped by 27% vs. the initial level; in patients with hypotension the change was only minimal. Pulmonary diastolic pressure began to drop from the 3rd minute after administration of the agents and the maximal decrease was attained after 30 min (34% of the initial value); even 4 hours after administration the values were below the initial level. The mentioned drug combination appears to be valuable especially in the first stage of treatment of cardiac asthma and pulmonary oedema. PMID- 3113826 TI - Idiotypic vaccinations: consideration towards a practical application. AB - We review the theoretical background as well as the available experimental data in animals and man on the possible use of anti-idiotypic antibodies as vaccines for the prevention of infectious diseases. In the first part, the basic experiments and concepts that fostered the idea of idiotypic vaccination are discussed. Although many basic aspects are still unknown, we conclude that the immune system can take antibody variable domains as representatives ("semiotypes") of foreign antigens not only in special cases, but also in a general sense. Among the major areas to be studied further are the events that regulate response to antibody in relation to those that regulate responses to antigen. Initial experiments suggest that responses to antibody may be directed intentionally towards a desired outcome. In the second part, we evaluate the actual medical need for idiotypic vaccination. We conclude that most novel vaccination regimes are likely to be developed with the help of protein chemistry and gene technology. Idiotypic vaccines may become applicable only in special, well-defined situations, such as cases of nonresponsiveness to antigen or cases of severe dysregulation of immunity by the antigen. The third part of the article deals with experimental models for idiotypic vaccination. A number of groups have performed protection experiments in various model infections of experimental animals using anti-idiotypic antibodies as vaccines. In a fair number of cases, involving infections with viral, bacterial, and parasitic microorganisms, protection has been successfully induced. In the fourth part, we summarize studies on idiotype expression in human antigen-driven immune responses. The limited data available suggest that human idiotype expression follows similar rules as in experimental animals. In particular, widely cross-relative idiotopes are readily detected using monoclonal anti-idiotopes. Antibodies to such idiotopes reacted with major proportions of the antibodies of a given specificity. Taken together, many factors point towards the feasibility of idiotypic vaccination. PMID- 3113828 TI - Fenoverine: a novel synchronizer of smooth muscle motility by interference with cellular calcium flow. AB - Several in vivo and in vitro test models were used to study the mechanism of action of fenoverine, a novel synchronizer of smooth muscle motility. In vivo, the effects of fenoverine were tested in the rabbit proximal colon, recording its ability to modify the electromyographic activity, either spontaneous or electrically elicited, in the presence or absence of atropine. Fenoverine did not influence the spontaneous motility nor did it modify the effects of atropine, but it significantly reduced the contractions elicited by electrical stimulation. In vitro, isolated rabbit and rat colon and isolated rat myometrium were used. In rabbit colon, fenoverine failed to influence the spontaneous motility as well as the effects of atropine, while significantly inhibiting the electrically elicited excitatory junction potential. Fenoverine also significantly inhibited the isometric contractions induced in rat myometrium and colon by electrical stimulation, by depolarization with hyperpotassic solution, as well as those induced by acetylcholine in calcium-free/EGTA medium, with ID50 ranging from 8.10(-7) to 3.1.10(-6) M except in the isolated colon following K+ depolarization (5.10(-5) M), all actions compatible with a calcium-modulating mechanism. Based on the reported data, it is concluded that fenoverine does not act as a muscarinic or opiate-receptor antagonist, but that its main mechanism of action is due to modulation of the calcium gradient across the muscular cell membrane by regulating the influx of the extracellular calcium and/or the release of the intracellular pool. PMID- 3113827 TI - Vitrification of mouse islets of Langerhans: comparison with a more conventional freezing method. AB - The possibility of cryopreservation of islets of Langerhans by vitrification using a mixture of cryoprotectants was investigated and the results were compared with a more conventional freezing method using Me2SO as cryoprotectant. Isolated mouse islets were divided into three groups: (1) control islets cultured for 6 days, (2) islets which were cryopreserved by vitrification after 2 days of culture, and (3) islets frozen in 1.5 M Me2SO after 2 days of culture. After warming, islets from groups 2 and 3 were cultured for 4 days. The thus treated islets were investigated with respect to insulin secretion in the presence of 2.5 or 25 mM glucose, survival during postwarming culture, morphology, and capability to reverse streptozotocin-induced diabetes. The insulin secretion in islets from all groups could be stimulated by a factor 5 or more by an increase in the concentration of glucose from 2.5 to 25 mM. The secretion of insulin in the presence of 2.5 mM glucose was similar in all groups of islets. The secretion of insulin in the presence of 25 mM glucose was slightly but not significantly lower in the cryopreserved islets than in the control noncryopreserved islets. The survival of islets during postwarming culture was comparable after cryopreservation with both methods, and islets from both groups could lower serum glucose in streptozotocin diabetic mice. We conclude that islets cryopreserved by the vitrification method are functional in vitro and in vivo. This method is quick, simple, and cheap because the use of complicated freezing equipment is avoided. PMID- 3113829 TI - Effects of chondroitin-4-sulphate on ultrastructure of ovarian granulosa cells. AB - Granulosa cells from medium sized porcine ovarian follicles exhibit inhibition of progesterone secretion after both 3 and 6 days of incubation in the presence of 2 mg chondroitin-4-sulphate (C-4-S)/ml. After 3 days of incubation some relatively small and undifferentiated granulosa cells are present in the above cultures. Six days following initiation of incubation in the presence of 2 mg C-4-S/ml many of the larger granulosa cells taken from medium sized follicles reveal lysis and/or resorption of material (probably lipoprotein) from their originally dense staining bodies as well as other indications of stress and degeneration. PMID- 3113830 TI - Hepatic uridine-diphosphate glucuronyl transferase activity of guinea pig with scurvy. AB - Ascorbic acid (AsA) concentrations in plasma exert a modulating effect on the activity of liver enzymes. Since UDP-glucuronyl transferase is a liver enzyme, which is responsible for bilirubin glucuronidation, the effect of varied amounts of AsA on this enzyme activity was studied. Sixty male guinea-pigs were randomly allocated to the following six groups: controls, scorbutic and groups given 2, 5, 10 or 20 mg of ascorbic acid, respectively. All the animals with the vitamin C deficient diet presented clinical signs of scurvy at the end of the experimental period, and had lost both body and liver weight compared to all other groups. Scorbutic animals had very low levels of AsA in the liver compared with controls (0.20 +/- 0.10 and 1.65 +/- 0.45 mg/g liver, respectively) (p less than 0.001). Liver AsA levels increased as the AsA dose increased. The UDP-glucuronyl transferase activity was lower in scorbutic animals than in controls (6.20 +/- 1.95 and 23.85 +/- 4.20 mg bilirubin/g protein/h, respectively) (p less than 0.001). The other groups C, D, E and F also had higher mean levels of UDP-GT activity than the scorbutic group B. Finally, no correlation was found between UDP-glucuronyl transferase activity and ascorbic acid intake. PMID- 3113831 TI - Identification of low-risk monitor admissions to medical-surgical ICUs. AB - A total of 5,790 intensive care unit (ICU) admissions from 13 tertiary care institutions were studied to identify patients who were at such low risk of receiving unique ICU therapies that admission might have been avoided or the length of ICU stay reduced. We used acute severity of disease on admission to the ICU along with the type of disease or surgery to risk stratify individual ICU patients. Among 1,941 patients who only received monitoring services on admission to the ICU, 1,358 (70 percent) were predicted to have less than a 10 percent risk of requiring subsequent active ICU treatment. Only 58 (4.3 percent) of these low risk patients actually received active treatment. The identification of low-risk patients was equally accurate in estimation and validation data sets. Our methods should allow physicians and hospitals to assess their current ICU utilization and, if appropriate, guide reductions in use. PMID- 3113832 TI - Cardiopulmonary function at maximum tolerable constant work rate exercise following human heart-lung transplantation. AB - Studies were performed measuring parameters of respiratory and circulatory function at rest and during maximum tolerable constant work rate treadmill exercise in 16 clinically well patients who had undergone heart-lung transplantation for end stage pulmonary hypertension. Ten patients were studied before and within eight weeks following transplantation. Long-term function with exercise was further evaluated with follow up studies at one year (n = 10) and two years (n = 6), posttransplantation. Posttransplant gas exchange and ventilation during exercise are essentially normal with neither being limiting to maximal exercise. Exercise capacity is significantly improved posttransplant, primarily as a result of improvement in the circulation over that found pretransplant in uncorrected pulmonary hypertension. Although improved, circulatory limitations of maximal exercise may still persist. Cardiorespiratory function at maximum tolerable exercise is well maintained following heart-lung transplantation for at least two years, providing no complications occur. This suggests that denervation of the heart and lungs, disruption of the bronchial circulation and pulmonary lymphatics, and the graft ischemia encountered at the time of transplantation impose no serious limitations on long-term cardiopulmonary function. The overall functional capacities of the transplanted heart and lungs are more than adequate for meeting the activities of normal life. PMID- 3113833 TI - Dependence of oxygen consumption on oxygen delivery in patients with chronic congestive heart failure. AB - We previously have shown that in patients with adult respiratory distress syndrome (ARDS) oxygen consumption (VO2) is linearly related to oxygen delivery (DO2) below a threshold DO2 of 21 ml/min/kg. To evaluate this relationship in chronic congestive heart failure (CHF), we studied eight patients with chronic CHF at baseline and during treatment with nitroglycerin. The resting DO2 and VO2 were 10.7 +/- 2.3 ml/min/kg and 3.8 +/- 0.87 ml/min/kg, respectively. In our eight patients, we found a significant relationship between changes in VO2 and in DO2 (delta VO2 = 0.16 + 0.34 X delta DO2, r = 0.84, n = 29). There was no significant relationship between DO2 and mixed venous oxygen tension (PvO2, r = 0.16), nor was there a significant relationship between cardiac output (Qt) and PvO2 (r = 0.21). We conclude that in patients with chronic CHF, changes in VO2 appear to be dependent on changes in DO2. This may represent an adaptive tissue response to chronically reduced systemic oxygen transport. PMID- 3113834 TI - Effect of PEEP on the arterial minus end-tidal carbon dioxide gradient. AB - The effect of PEEP on the arterial minus end-tidal carbon dioxide gradient (PaCO2 PetCO2) was evaluated in 13 adult patients with acute respiratory failure. The morphologic study of the pressure-volume (P-V) curves allowed separation of the patients into two groups: group 1 (n = 7) with initial inflection point in the (P V) curve, and group 2 without inflection point. We hypothesized that the profile of the PaCO2-PetCO2 gradient would indicate an appropriate PEEP level only in patients with recruitable air spaces. We ventilated group 1 patients with zero end expiratory pressure (ZEEP), PEEP corresponding to inflection point pressure (PEEPPi) and PEEP5 cm H2O above PEEPPi, and group 2 patients with ZEEP, 6 cm H2O PEEP and 12 cm H2O PEEP. The PaCO2-PetCO2 gradient changed significantly in group 1 (ZEEP: 13.59 mm Hg; PEEPPi: 8.33 mm Hg; PEEPPi + 5 cm H2O: 10.54 mm Hg), but not in group 2 (ZEEP: 14.15 mm Hg; PEEP 6 cm H2O: 14.20 mm Hg; PEEP 12 cm H2O: 16.53 mm Hg). Our results show that the PaCO2-PetCO2 gradient may be useful in selecting a PEEP level which produces alveolar recruitment, but only in those patients with initial inflection point in the P-V curve. PMID- 3113835 TI - Long-term ventilator care. A Chicago problem and a national problem. AB - Patients who require long-term ventilator care in an acute care setting may have a problem because diagnosis-related group (DRG) payments are less than the cost of their medical care. An alternative for quality medical care at lower cost includes admission to a long-term ventilator facility. In Chicago, only two dedicated long-term ventilator programs exist, with only 33 beds. Within 50 to 150 miles of the immediate Chicago area are three more units, with only 42 operational beds. All of the long-term care beds are full, and over 50 patients await transfer. Since acute care is reimbursed on a DRG designation and long-term ventilator care has no DRG category, there is a bias in acute care settings against these patients. Medicare patients are reimbursed up to 100 days, after which patients become eligible for public aid. Unfortunately, long-term ventilator patients often wait in acute care settings for this 100 days to elapse, even though medical care may be superior in a long-term ventilator unit. In addition to not providing the best care, this situation is economically wasteful. Solutions to these problems will require a coordinated national, state, and local plan. National medical societies should be consulted regarding solutions to health care problems that provide the best medical care at a reasonable cost for patients on long-term ventilation. PMID- 3113836 TI - Flecainide-induced sustained ventricular tachycardia successfully treated with lidocaine. AB - A 69-year-old man had new sustained ventricular tachycardia caused by flecainide which promptly responded to intravenous lidocaine therapy. Discontinuation of the lidocaine infusion resulted in the reappearance of ventricular tachycardia which again immediately terminated after lidocaine was given. In this case, lidocaine effectively reversed the proarrhythmic effects of flecainide. PMID- 3113837 TI - Intra-Hisian block associated with unusual etiologies. PMID- 3113839 TI - Subtotal laryngectomy and immediate extensive reconstruction with cervical skin flap. PMID- 3113838 TI - The effect of oxygen intoxication on the morphology of intercellular junctions of pulmonary endothelium and alveolar epithelium. A freeze-fracture study. PMID- 3113840 TI - Activation of natural killer cells with 3,6-bis (2-piperidinoethoxy) acridine trihydrochloride (CL 246, 738). PMID- 3113842 TI - Lipoprotein and apoprotein A1 levels in diabetics and coronary heart disease patients and controls. PMID- 3113841 TI - Chromosomal analysis of a human lung adenocarcinoma cell line, AGZY83-A. PMID- 3113843 TI - Significance of cerebrospinal fluid ferritin estimation in central nervous system leukemia. PMID- 3113844 TI - Effect of thyroid hormone dosage on thyroid function tests in T4-replaced hypothyroid patients. PMID- 3113846 TI - Experimental study of pigment gallstone formation and dissolution. PMID- 3113845 TI - Chinical experience with levonorgestrel and ethinyl estradiol in Beijing. PMID- 3113847 TI - Establishment of a natural mating colony of Anopheles dirus Peyton ET Harrison and their biological characteristics. PMID- 3113848 TI - Clinical analysis of 86 cases of carcinoma of the lip. PMID- 3113849 TI - HLA antigen distribution and haplotype segregation in Chinese patients with psoriasis. PMID- 3113850 TI - Experimental investigation of the antihypercholesteremic element separated from the Chinese medicinal herb Drynaria fortunei (Kunze) J, SM. PMID- 3113851 TI - Further characterization of HLA-SH6 antigen in Chinese. SH6 is identical to ST-16 antigen. PMID- 3113852 TI - Three euchromatic DNA sequences under-replicated in polytene chromosomes of Drosophila are localized in constrictions and ectopic fibers. AB - We examined three regions of under-represented euchromatic DNA sequences (histone, Ubx, and 11 A), for their possible correlation with euchromatic constrictions in polytene chromosomes of Drosophila melanogaster. Cloned sequences were hybridized to filters and to chromosomes prepared for light microscopy. Under-represented sequences hybridized to DNA within constrictions and in ectopic fibers. In contrast, adjacent sequences that were fully endoreplicated in the Ubx and 11 A regions in polytene cells hybridized to sites just adjacent to their respective constrictions. For one region (Ubx), sequences under-represented in salivary gland cells were fully endoreplicated in fat body cells. For this particular region, the morphology of the polytene chromosomes differs between these two cell types in that the specific constriction is absent at this region in fat body polytene chromosomes, thus strengthening the correlation between under-representation and chromosome constrictions. Although all three sequences are in regions that have been classified by others as "intercalary heterochromatin," we detect no common functional or sequence organizational feature for these examples of under-represented DNA. We suggest that the lower efficiencies of the replication origins, or special regions of termination at these sites, are the primary cause of the under-replication, and that this under-replication is sufficient to confer the properties of intercalary heterochromatin. PMID- 3113853 TI - [Determination of lactase deficiency by the hydrogen breath test: a study of 198 healthy Chinese subjects]. PMID- 3113854 TI - [Lactose malabsorption and its ethnic influence in healthy Chinese]. PMID- 3113855 TI - [Preliminary study on the detection of tuberculosis antibodies in ascites with enzyme-linked immunosorbent]. PMID- 3113856 TI - [Hypothalamus-pituitary-thyroid axis in patients with hepatic cirrhosis]. PMID- 3113857 TI - [Changes in ECG and serum electrolytes in lithium therapy]. PMID- 3113858 TI - [Retrospect and prospect of treating ischemic cerebral apoplexy in the acute stage (with an analysis of 655 cases)]. PMID- 3113859 TI - [Clearance of fat emulsions and dual energy source in total parenteral nutrition support in post trauma/sepsis patients]. PMID- 3113860 TI - [Technic and complications of the argon laser in the treatment of angle-closure glaucoma]. PMID- 3113861 TI - [Diagnostic value of the retinal nerve fiber layer defect in primary open-angle glaucoma]. PMID- 3113862 TI - [Inheritance of the cup/disc ratio and its clinical significance]. PMID- 3113863 TI - [The cup/disc ratio in twins--a study of C/D ratio heredity]. PMID- 3113864 TI - [Correction of severe exotropia by the unilateral 4-muscle operation]. PMID- 3113865 TI - [Determination of immunoglobulins and complement C3 in the subretinal fluid]. PMID- 3113866 TI - [Disruption of the blood-aqueous barrier after dye-laser iridectomy]. PMID- 3113867 TI - [Experimental studies on the development and reversal of galactose cataracts]. PMID- 3113868 TI - [Modes of hereditary transmission of congenital primary nystagmus]. PMID- 3113870 TI - [Visual field in early glaucoma and the correlation of optic disc changes with visual field defects]. PMID- 3113871 TI - [Scanning electron microscopy of the corrosion cast of the blood vessels of the uvea: I. Angioarchitecture of the iris and ciliary body]. PMID- 3113869 TI - [The ductus nasolacrimalis membranosus in Chinese adults]. PMID- 3113872 TI - [Evaluation of the therapeutic effect of penetrating keratoplasty in herpes simplex keratitis]. PMID- 3113873 TI - [Determination of tear lysozyme in herpes simplex keratitis]. PMID- 3113874 TI - [Treatment of Mooren's ulcer by conjunctival and subconjunctival excision]. PMID- 3113875 TI - [Argon laser treatment of primary open-angle glaucoma]. PMID- 3113876 TI - [Steroid glaucoma induced by subconjunctival injection of prednisolone]. PMID- 3113877 TI - [Copper and zinc metabolism in primary retinitis pigmentosa]. PMID- 3113878 TI - [Surgical treatment of congenital jerking nystagmus]. PMID- 3113879 TI - [Treatment of childhood amblyopia by red and white stripes]. PMID- 3113880 TI - [Clinical use of the spectacle magnifier]. PMID- 3113881 TI - [Scanning electron microscopy of laser-induced retinal damage]. PMID- 3113882 TI - [Aqueous penetration of subconjunctival gentamycin]. PMID- 3113883 TI - [Drusen of the optic disk (report of 25 cases)]. PMID- 3113884 TI - [ERG in proliferative diabetic retinopathy after photocoagulation]. PMID- 3113885 TI - [Clinical significance of papilledema with extensive fundus hemorrhages caused by raised intracranial pressure]. PMID- 3113886 TI - [Refractive errors and peripheral retinal degeneration]. PMID- 3113887 TI - [Indirect ophthalmoscopy with greater magnification]. PMID- 3113888 TI - [Determination of visual acuity by laser interference fringes]. PMID- 3113889 TI - [The endothelium in herpes simplex keratitis]. PMID- 3113890 TI - [Copper content of the ocular iontophoretic fluid and ERG study of intraocular copper foreign bodies]. PMID- 3113891 TI - [Surgical correction of upper eyelid retraction]. PMID- 3113892 TI - [Clinical evaluation of sodium cromproxate in vernal keratoconjunctivitis]. PMID- 3113893 TI - [Retinal hemorrhage in 212 cases of highland neonates]. PMID- 3113894 TI - [Prospective study on the preliminary evaluation of a tuberculosis susceptibility test with the micro-culture dish method using native products]. PMID- 3113895 TI - An improved method for the immunocytochemical detection of bromodeoxyuridine labeled nuclei using flow cytometry. AB - A new staining protocol is described for the immunocytochemical detection of BrdUrd labeled nuclei. Pepsin treatment of ethanol fixed cells or tissue, followed by DNA denaturation at low pH, resulted in increased sensitivity of BrdUrd staining comparable to the thermal denaturation protocol, and decreased background binding. This technique is applicable to cell suspensions, including cultured cells and bone marrow cells. Furthermore, pepsin digestion of ethanol fixed tissue fragments resulted in a high recovery of nuclei in which incorporated BrdUrd could be detected. This possibility, together with the high sensitivity, make this method especially suitable for cell kinetic studies of human solid tumors in vivo. PMID- 3113896 TI - Anomalous behaviour of forward and perpendicular light scattering of a cyanobacterium owing to intracellular gas vacuoles. AB - Extinction, absorption, and forward and perpendicular light scatter of the blue green alga Microcystis aeruginosa with different amounts of intracellular gas vacuoles were determined. The amount of gas vacuoles in the cells was controlled by application of pressure. The presence of the gas vacuoles caused a tenfold increase in perpendicular light scatter, and a fivefold decrease in forward light scatter as measured by flow cytometry. Chlorophyll fluorescence showed a 16% decrease. The presence of gas vacuoles did not affect the size of the algae. The absorption spectrum of Microcystis aeruginosa was slightly raised but practically not distorted by the gas vacuoles. The attenuation spectrum, a measure for light extinction by the algal cells, was significantly distorted. The increase of perpendicular light scatter intensity of the cells is a direct consequence of the relatively high scatter of each vacuole, whereas the forward light scatter decrease is attributed to a lower phase-shift factor rho of the whole cells, caused by the intact gas vacuoles. PMID- 3113897 TI - Discrimination of viable and non-viable cells using propidium iodide in two color immunofluorescence. AB - The relative ease with which a flow cytometer can perform simultaneous two color immunofluorescence to examine subpopulations of lymphoid cells has been well documented. Thus, flow cytometers equipped with only a single argon laser can be used to delineate various cell types by exciting both fluorescein- and phycoerythrin-conjugated antibodies to cell surface antigens. One problem that remains, however, is the artifactual staining of dead cells and clumps, which cannot be distinguished from viable cells on the basis of cell surface staining characteristics. We describe a method for simultaneous two color analysis or sorting of viable leukocytes which requires only a single laser. The method utilizes propidium iodide, which stains dead cells and thereby excludes such cells from the analysis. Using this method, as many as four viable cell types have been simultaneously analyzed in a single sample. PMID- 3113898 TI - Solitary diverticulum of the cecum and right colon. Report of six cases. AB - Diverticulum of the cecum is a rare, benign, generally asymptomatic lesion that manifests itself only following inflammatory or hemorrhagic complications. A personal series of six cases discusses the difficulty of differential diagnosis at both the preoperative and intraoperative levels. The preferable treatment is simple resection. PMID- 3113899 TI - Insulin resistance and insulin-dependent diabetes mellitus. PMID- 3113900 TI - Intracardiac insulin injection as treatment of cardiac arrest due to hyperkalemia in diabetic ketoacidotic patient. PMID- 3113901 TI - Euglycemic diabetic ketoacidosis in Duchenne's muscular dystrophy. PMID- 3113902 TI - Computers: participate and win. PMID- 3113903 TI - Designing for dentistry. PMID- 3113904 TI - Evaluation of insulin pump treatment under routine conditions. AB - Sixty-six patients with insulin-dependent diabetes mellitus (IDDM) initiated insulin pump treatment under routine conditions. Four patients (6%) discontinued treatment. One patient died. 61 patients were followed for a total period of 130 patient years. A sustained decrease in HbA1c was obtained during insulin pump treatment. The frequency of the following acute side effects was: ketoacidosis 0.06 episodes per patient per year, severe hypoglycaemia 0.09 episodes per patient per year and infection at the injection site 0.06 episodes per patient per year. Insulin pump treatment was well accepted by the patients; all but one wanted to continue insulin pump treatment. The major advantages were greater quality of life, greater flexibility as to meal times and better blood glucose regulation. The major disadvantages were technical problems: blockage of the infusion system, greater treatment expenses and the large pump size. We conclude that insulin pump treatment is well accepted as long-term treatment in selected IDDM patients. The improvement in metabolic control can be sustained through several years, and the frequency of severe hypoglycaemia during pump treatment is comparable to that of conventional insulin treatment. The risk of ketoacidosis requires more attention from the physician. PMID- 3113905 TI - [Differences in the specificity of the protective effect of natural and recombinant interferons against mutagens]. PMID- 3113906 TI - [Molecular cloning of the glucoamylase gene STA2 of the yeast Saccharomyces diastaticus CBS1782]. PMID- 3113907 TI - The effect of carbon dioxide on the in vitro activity of erythromycin and RU 28965 against anaerobic bacteria. AB - The in vitro activity of erythromycin and RU-28965 (a novel macrolide antimicrobial with improved pharmacokinetics) was determined against a variety of anaerobic bacteria in anaerobic atmospheres with and without added carbon dioxide. Minimum inhibitory concentrations (MIC) were determined using an antimicrobial incorporation technique in Wilkins-Chalgren agar (Oxoid, UK) containing saponinlysed horse blood to a final concentration of 10%. The inoculum used was approximately 10(4) colony forming units (cfu) contained in 10 microliters Wilkins-Chalgren broth, which was applied to the surface of the agar plates using a multipoint inoculator. Following inoculation, plates were incubated for 48 h at 37 degrees C in an anaerobic atmosphere containing 10% carbon dioxide or in hydrogen alone. The MIC of each antimicrobial for each organism examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentrations required to inhibit the growth of 50% (MIC50) and 90% (MIC90) of the bacteria examined were also determined. The MICs of erythromycin and RU-28965 for isolates of the Bacteroides fragilis group, B. bivius and Fusobacterium spp. were generally 10-100 times greater when determined in the presence of carbon dioxide than when determined in hydrogen alone. The MICs of erythromycin and RU-28965 for B. melaninogenicus, Peptococcus spp., Peptostreptococcus spp., Clostridium perfringens, Cl. difficile and Propionibacterium acnes were less affected by the presence of carbon dioxide. PMID- 3113908 TI - [Ambulatory parenteral nutrition in short bowel syndrome: a retrospective study]. AB - Parenteral nutrition via an indwelling central venous catheter was undertaken at home over a total period of 24,747 days in 34 patients with the short-bowel syndrome (of various causes). In some of the patients there developed complete adaptation of the residual intestine so that parenteral nutrition could be terminated. Complications were: infection, thrombosis, pulmonary embolism and metabolic problems. But the method proved to be suitable for improving the quality of life of these patients. PMID- 3113909 TI - Historical aspects of nitrate therapy. AB - The exciting story of the development of nitrates as drugs in clinical medicine is briefly reviewed. Glyceryl trinitrate (nitroglycerin) was synthesised by Sombrero in 1847. Amyl nitrite was discovered a few years later and was used by Guthrie in 1859. The first report on the action of glyceryl trinitrate and amyl nitrite was published by Brunton in 1867, and further papers were published by Murell in 1879. Organic nitrates appeared in the 1930s. Krantz and co-workers synthesised and used mannide dinitrate, which was longer acting than the nitrates that had been used previously. Research on a similar drug, isosorbide dinitrate, was initiated by Porje in Stockholm. The drug was first marketed in Sweden in 1946. Isosorbide dinitrate was independently synthesised in the United States by Harris and colleagues in the 1950s. The drug was used fairly extensively on both sides of the Atlantic. However, there was a temporary decrease in popularity around 1970 when Needleman and colleages reported oral nitrates to be of questionable value, as they underwent rapid biotransformation during first-pass metabolism in the liver. This opinion was later altered and today the drug enjoys worldwide acceptance in different formulations. Also, in recent years one of the active metabolites, isosorbide 5-mononitrate, has been marketed as an effective antianginal drug. PMID- 3113910 TI - Pharmacokinetics of various preparations of organic nitrates. AB - The pharmacokinetics of different formulations of glyceryl trinitrate, isosorbide dinitrate, isosorbide 5-mononitrate and isosorbide 2-mononitrate are reviewed. PMID- 3113911 TI - Treatment of acute anginal attacks with nitrates. AB - This article reviews the author's published experimental studies on the pharmacodynamic and clinical effects of different glyceryl trinitrate formulations in man. PMID- 3113912 TI - Determination of nitrates in plasma. AB - Because of the high efficacy of existing nitrates, alternative dosage formulations have been developed rather than new compounds. These new formulations challenge the analyst to develop analytical methods with lower sensitivity and higher precision. Isosorbide dinitrate is analysed in the presence of its major metabolites isosorbide 2-mononitrate and isosorbide 5 mononitrate. The present method is an improvement over previously published methods. It is not possible to analyse glyceryl trinitrate and its major metabolites 1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate with the necessary sensitivity in one chromatogram. A 2-step procedure is therefore applied. The extraction procedures, the gas chromatographic conditions, imprecision and inaccuracy of the methods, the lower limits of quantitation, sample chromatograms and applications of all methods are described in detail. Thus, the possibilities of modern analytical methods in the determination of nitrates in the lower picogram region are demonstrated. PMID- 3113913 TI - Buccal versus sublingual glyceryl trinitrate administration in the treatment of angina pectoris. A Swedish multicentre study. AB - 126 patients with chronic exercise-induced angina, who were accustomed to the use of sublingual glyceryl trinitrate, were entered into a multicentre 2-week crossover comparison of sublingual (Nitromex) and buccal (Suscard) formulations of glyceryl trinitrate. Before randomisation the patients underwent a training period when doses of the buccal formulation were individualised. There were 31% fewer attacks with the buccal formulation, and more patients reported higher physical activity on the buccal compared with the sublingual formulation (30% vs 16%). The buccal formulation was also more effective when glyceryl trinitrate was used prophylactically to prevent expected attacks, being effective in 74% of attempts compared with 66% for the sublingual formulation (p less than 0.05). More patients preferred the buccal route of administration for prophylactic use (81% vs 4%, p less than 0.05). Similarly, when asked to select which they would use in future, 65% of patients preferred the buccal formulations (p less than 0.05), 19% preferred sublingual glyceryl trinitrate, and 16% did not express any preference. PMID- 3113914 TI - The use of the ELISA test for the immunodiagnosis of Schistosoma mansoni infection: the Zambian experience. PMID- 3113915 TI - The association of chronic hepatitis B infection with chronic Schistosomiasis mansoni in Kenya. PMID- 3113916 TI - [Bone marrow aplasia: a rare complication in virus-induced hepatitis]. AB - Bone marrow aplasia associated with acute viral hepatitis is a rare, in the rule late complication. A prognostic relation between the latency of acute hepatitis and the development of aplastic anemia is described. We report a case of nearly symptomless hepatitis in a 25 year old women with a fatal course of aplastic anemia. First clinical symptoms were caused by aplastic anemia. The pathogenesis of aplastic anemia associated to viral hepatitis is obscure. Genetic and immunological causes are discussed. A direct viral action is possible. Because the main part of the described cases is caused by non-A, non-B hepatitis, it seems apparent that at least a non-A, non-B virus strain could have an affinity to bone marrow cells. Ensuring this, relations will be impossible up to the identification of the virus. PMID- 3113917 TI - An improved in vitro bioassay for follicle-stimulating hormone (FSH): suitable for measurement of FSH in unextracted human serum. AB - FSH bioactivity was measured by means of FSH-dependent aromatase activity (conversion of androgen substrate to estradiol). Assay sensitivity was optimized by the use of immature (7-10 days old) rats as Sertoli cell donors, serum-free medium for incubation, phosphodiesterase inhibitor (methylisobutylxanthinine), serial dilution of FSH in medium containing 1% BSA, delayed addition of FSH for 72 h after cell plating, and 19-hydroxyandrostenedione (2.5 X 10(-6) M) as the aromatizable androgen substrate. The method consisted of subjecting the decapsulated immature rat testes to a 2-step collagenase dispersion, plating the cells in medium [Dulbecco's Modified Eagle's Medium-Ham's F-10 (1:1)] containing growth factors and methylisobutylxanthinine for 72 h, adding increasing doses of FSH to the standard curve or small volumes of serum to the test vials as well as 19-hydroxyandrostenedione for 24 h, and measuring estradiol by RIA in dilutions of the medium. Using NIAMDD human (h) FSH-2 as the bioassay standard, the useful range of the assay was 0.01-5.0 ng/ml. Specificity was determined by the addition of graded doses of hLH, hTSH, ACTH, hGH, hPRL, and hCG. The minor degree of FSH bioactivity observed in a few hormone preparations was accounted for by the degree of FSH contamination in them. Mean intra- and interassay coefficients of variation were 9% and 11%, and the index of precision was 0.049. This bioassay was used to determine the bioactive FSH content of pituitary extracts, tissue culture media, elutions from columns, and isoelectrically focused samples. More importantly, small quantities of human sera gave responses parallel to the standard curve in a minimum of two dilutions. The bio- to immunoreactive ratios, expressed as the mean +/- SEM (NIAMDD-hFSH-2), were 0.66 +/- 0.2 in boys (n = 6), 0.78 +/- 0.2 in pubertal girls (n = 6), 1.18 +/- 0.2 in men (n = 13), 1.24 +/- 0.1 in postmenopausal women (n = 30), 1.94 +/- 0.3 in the follicular phase (n = 19), 6.2 +/- 1.4 in the ovulatory phase (n = 19), and 1.6 +/- 0.4 in the luteal phase (n = 19) of the normal menstrual cycle. These results indicate that the bio to immunoreactive hFSH ratio in the circulation, is dependent upon the hormonal milieu of the subject. PMID- 3113918 TI - 1,25-Dihydroxyvitamin D3 enhances thyrotropin releasing hormone induced thyrotropin secretion in normal pituitary cells. AB - The findings of specific binding of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in normal rat pituitary tissue and selective effects of 1,25-(OH)2D3 on gene expression in clonal pituitary tumour cells have suggested that vitamin D may regulate pituitary function. Therefore, the in vitro effect of 1,25-(OH)2D3 on normal pituitary cells was investigated. Primary anterior pituitary cell cultures prepared from female rats were maintained in experimental medium +/- 10(-8) M 1,25-(OH)2D3 for up to 24 h and then incubated with fresh experimental medium containing TRH (10(-10)-10(-8) M) or vehicle for 1 h. Pretreatment with 1,25 (OH)2D3 for 24 h led to increased TSH release at all TRH concentrations tested (P less than 0.0001), a decrease in the half-maximal stimulatory dose of TRH for TSH release from 2 X 10(-9) M to 0.4 X 10(-9) M, a 22% increase in maximal TSH release (P less than 0.01), and an 81% increase in TSH release at 10(-9) M TRH (P less than 0.001). 1 X 10(-9) M 1,25-(OH)2D3 increased TRH (10(-9) M)-induced TSH release by 20% (P less than 0.05) but 10(-7) M and 10(-6) M 25-hydroxyvitamin D3 (25-OH D3) had no effect. The effect of 1,25-(OH)2D3 on TRH (10(-9) M)-induced TSH release was evident within 8 h and was maximal by 16 h. There was no effect on basal TSH release, TSH accumulation in the medium in the preceding 24 h nor on cell-associated TSH. 1,25-(OH)2D3 pretreatment had no effect on TRH-induced PRL secretion, PRL accumulation in the medium nor on cell-associated PRL. We have shown that 1,25-(OH)2D3 acts selectively on the thyrotroph to enhance in vitro responsiveness to physiologically relevant concentrations of TRH. These findings are consistent with the reported autoradiographic localization of [3H]-1,25 (OH)2D3 in the thyrotroph and support a permissive or regulatory role of vitamin D in the normal pituitary gland. PMID- 3113919 TI - Endogenous opioid peptides modulate the effect of corticotropin-releasing factor on gonadotropin release in the primate. AB - Stress can induce endocrine abnormalities and menstrual dysfunction in the primate. Here, we examine the effects that CRF, the principal neurohormone in control of the hypothalamic-pituitary-adrenal axis, exerts on pulsatile gonadotropin secretion and the role that the endogenous opioid peptides may play in this phenomenon. Ovariectomized rhesus monkeys were given a 5-h continuous iv infusion of physiological saline (2 ml/h), human CRF (100 micrograms/2 ml . h), or hCRF plus the opiate receptor antagonist naloxone (2 mg/2 ml/h; 5 mg in two experiments; n = 7 experiments/group). LH and FSH concentrations were measured at 15-min intervals for a 3-h preinfusion baseline control, during the 5-h infusion, and during a 2-h postinfusion observation period, while cortisol concentrations were measured at frequent intervals during the entire experiment. CRF infusion produced a progressive and significant decrease in both LH and FSH. Mean areas (+/- SE) under the LH and FSH curves during the 5-h CRF infusion, expressed as a percentage of preinfusion baseline, were 59.9 +/- 4.6% and 83.0 +/- 3.1% (+/- SE), respectively (P less than 0.001 and P less than 0.01 vs. saline controls). Large amplitude LH pulses were abolished during the CRF infusion. However, after cessation of CRF infusion, there was a rapid resumption of LH pulsatile release in four of the seven experiments. Addition of naloxone to CRF prevented the CRF mediated suppression of LH and FSH release. Mean areas for LH and FSH during the 5-h combined infusion were 100.3 +/- 6.6% and 99.6 +/- 4.3% of the preinfusion baseline, respectively (P less than 0.001 and P less than 0.05 vs. CRH alone; NS vs. saline), and pulsatile LH secretion was maintained. Regardless of whether naloxone was administered, CRF increased cortisol levels significantly. Mean cortisol levels at the end of the CRF and CRF plus naloxone infusions were 48.2 +/- 10.4 and 52.9 +/- 7.4 micrograms/dl (+/- SE), respectively, compared to 21.0 +/- 3.0 with saline (P less than 0.05). These results demonstrate that in the ovariectomized rhesus monkey, CRF suppresses the secretion of both LH and FSH, and this effect can be sustained. They also indicate that the CRF inhibitory action on gonadotropin is primarily mediated by endogenous opioid peptides, independent of glucocorticoid levels. PMID- 3113920 TI - Evidence for a dual effect of gamma-aminobutyric acid on thyrotropin (TSH) releasing hormone-induced TSH release from perifused rat pituitaries. AB - The effects of gamma-aminobutyric acid (GABA) on the spontaneous and TRH-induced TSH release were investigated in vitro on perifused rat pituitaries. The dynamic pattern of TSH release was measured in response to a 6-min pulse of TRH (10 nM) with or without GABA addition. GABA had no effect on spontaneous TSH release but exhibited a dual effect on TSH-stimulated release according to the dose (as calculated by the induced-basal ratio): a potentiation of the TSH response to TRH at the lowest concentrations tested (less than or equal to 10 nM) and an inhibition for GABA concentrations equal or higher than 100 nM. The GABA potentiation was mimicked by muscimol (10 microM) and isoguvacine (10 nM) but not by baclofen (1 microM). Bicucullin (1 microM) or picrotoxin (1 microM) added 15 min before GABA was unable to reverse the GABA potentiation of the TSH response, although SR 95103 (1 and 10 microM), a specific GABA A antagonist, partially or totally antagonized this response. Diazepam (7 nM) was able to potentiate the TSH response by 216% when GABA was added to the system at a concentration (60 nM) which does not modify by itself the TSH response. The inhibitory effect of GABA (100 nM) was completely abolished by bicucullin (1 microM), by picrotoxin (1 microM), and by SR 95103 (1 microM). Picrotoxin not only blocked the inhibitory action of GABA but significantly (P less than 0.05) potentiated the TSH response to TRH. Our data suggest a dual GABA-ergic control of TRH-stimulated TSH release directly on the pituitary, probably mediated by two different kinds of GABA receptors: a GABA A receptor site mediating the inhibitory effect and a nonclassical GABA A receptor site of higher affinity for its stimulatory action. PMID- 3113921 TI - Pulsatile release of gonadotropin-releasing hormone (GnRH) from the rat hypothalamus in vitro: calcium and glucose dependency and inhibition by superactive GnRH analogs. AB - We have shown previously that the rat hypothalamus retains in vitro its capacity of generating pulsatile release of GnRH. The present study evaluated if pulsatile release of GnRH in vitro was influenced by metabolic conditions (calcium and glucose availability) and the possible self-regulatory role of GnRH in its pulsatile secretion. In the presence of a calcium-chelating agent (EGTA, 20 mM) or a calcium-channel blocker (D-600, 0.1 mM), the release of GnRH induced by a depolarization (veratridine, 50 microM) was markedly and reversibly decreased. In addition, frequency and amplitude of GnRH secretory pulses were significantly reduced (P less than 0.05). When glucose use was inhibited using 2-deoxyglucose (5.6 mM) the release of GnRH induced by veratridine and the frequency of GnRH pulses were also blunted (P less than 0.05). Superactive agonists of GnRH (Buserelin and D-TRP6-PRO9-N-ET, 10 nM) caused a prompt decrease of GnRH release in basal conditions and in the presence of veratridine. A significant inhibition (P less than 0.05) was observed using buserelin concentrations greater than 0.01 nM, whereas two GnRH analogs without biopotency (Leu8-GnRH, Des-gly10-N picolylamide GnRH, 100 nM) did not affect GnRH release. The two agonists of GnRH reduced by 43% to 66% (P less than 0.05) the occurrence of significant GnRH pulses. We conclude that, in vitro, the hypothalamic neuronal circuitry resulting in GnRH pulsatile secretion is dependent on calcium and glucose availability and is sensitive to an ultrashort-loop inhibitory feedback mechanism. PMID- 3113922 TI - HLA-DR antigen expression on intrathyroidal lymphocytes and thyrocytes in Hashimoto's thyroiditis and Graves' disease: an immunohistological study. AB - In frozen sections of thyroid glands with Hashimoto's thyroiditis (HT) and Graves' disease (GD), infiltrating lymphocytes were tested for their expression of HLA-DR antigens as a marker of in situ activation. In a combination of indirect immunoperoxidase and direct immunofluorescence staining, most of the immunoglobulin D positive mature B cells were found to be DR positive (DR+) in both diseases. In HT, sizable portions of both helper/inducer T (Leu3+) and suppressor/cytotoxic T (Leu2+) cells were DR+ in interfollicular regions as well as in lymphocyte clusters and lymphoid follicles. In GD, the proportion of DR+ cells in the interfollicular Leu2+ population was significantly lower than that of HT. DR+ thyrocytes were seen in all 14 cases of HT and in 14 out of 16 cases of GD, especially in the vicinity of lymphocyte aggregates. The extent of their DR expression was not correlated with the percentage of DR+ cells in either T subset. These results indicate that a significant portion of infiltrating T cells are activated in autoimmune thyroid diseases, and there may be bidirectional interaction between DR+ thyrocytes and DR+ T cells. The difference in frequency of Leu2+ DR+ cells may account for the difference between the immunopathological features of HT and GD. PMID- 3113923 TI - Benign occipital epilepsy: a family study. AB - Benign occipital epilepsy is a newly recognized form of partial epilepsy in children. It is characterized by motor seizures preceded in some cases by visual symptoms and a relatively benign course. We present three siblings with this condition and a fourth with the EEG abnormalities. A family study including 25 relatives demonstrated a typical EEG abnormality in 26% of relatives. These EEG changes were more evident in younger members. These findings suggest an autosomal dominant pattern for the EEG abnormalities with age-dependent expression and variable penetrance of the seizure disorder. PMID- 3113925 TI - Epilepsia partialis continua in Sjogren's syndrome. AB - Epilepsia partialis continua with Sjogren's syndrome is reported. The patient had extensive involvement of the nervous system with left middle cerebral artery occlusive stroke, mononeuritis multiplex, right partial sensory motor seizures and epilepsia partialis continua involving the right big toe and foot. The EEG showed nonspecific bilateral theta slowing. The epilepsia partialis continua did not respond to antiepileptic drugs. PMID- 3113924 TI - Status epilepticus of benign partial epilepsies in children: report of two cases. AB - Benign partial epilepsies of childhood (BPEC) are one of the most frequent types of epilepsy in school-age children. Status epilepticus (SE) of these conditions have not yet been reported. Two children with clinical and EEG features consistent with the diagnosis of BPEC-SE are presented. In neither case did SE respond to current antiepileptic medications and stopped only after administration of steroids. At follow-up 1 and 2 years post SE, neurologic and intellectual development have been normal. Differential diagnoses included an atypical benign partial epilepsy, epilepsy with electrical status epilepticus during slow sleep, acquired epileptic aphasia, Lennox-Gastaut syndrome and epilepsia partialis continua. PMID- 3113926 TI - Hepatotoxicity in rat following administration of valproic acid: effect of L carnitine supplementation. AB - The effect of prolonged administration (7 days) of valproate (VPA, 500 mg/kg/day), or VPA (500 mg/kg/day) with L-carnitine (200 mg/kg/day) on blood carnitine levels and the appearance of liver mitochondria were assessed in the rat. VPA-treated rats showed hypocarnitinemia and enlarged mitochondria when compared with saline-injected control rats. In rats treated with both VPA and L carnitine, serum and liver carnitine levels were increased by the L-carnitine supplement and the liver mitochondria were not enlarged. L-Carnitine supplement in VPA-medicated patients seems to prevent hepatotoxicity, especially mitochondrial dysfunction. PMID- 3113927 TI - Differences between two feline epilepsy models in sleep and waking state disorders, state dependency of seizures and seizure susceptibility: amygdala kindling interferes with systemic penicillin epilepsy. AB - The objective of the study was to determine whether contemporary feline models of petit mal (systemic penicillin epilepsy) or temporal lobe epilepsy (amygdala kindling) resemble human seizure disorders with respect to disturbances of sleep and waking states, the state dependency of seizures, and transference of seizure susceptibility. These variables were examined in 6-h polygraphic recordings before and during exposure to both seizure models in 24 cats; 12 cats had intramuscular (i.m.) injections of 300,000 or 400,000 IU/kg of penicillin prior to kindling, and 12 were kindled before penicillin challenge. Results were as follows. First, penicillin increased light slow wave sleep (SWS) and drowsiness, during which spike-wave (SW) activity was maximal. Generalized tonic-clonic convulsions (GTCs) occurred predominantly in drowsiness after awakening from SWS. Second, kindling produced more deep SWS than did penicillin; susceptibility to kindled GTCs peaked during deep SWS, especially in transition to rapid eye movement sleep (REM). Third, penicillin did not influence subsequent sleep disorders or seizure susceptibility during kindling; kindling interfered with penicillin-induced GTCs, SW activity, and sleep disorders. Collectively, the findings suggest distinct state disorders and state-dependent seizure profiles in the two models. These differences parallel human analogues and may have contributed to the transference results. Kindling is a chronic model with persistent sleep and seizure abnormalities that differ from and may have discouraged penicillin epilepsy. Penicillin is an acute model with transient state and seizure disorders, a fact that may account for the absence of penicillin transference to kindling. PMID- 3113928 TI - Caffeine blocks absence seizures in the tottering mutant mouse. AB - The neurological tottering mutant mouse is characterized by frequent "absence" seizures accompanied by bilateral synchronous spike and wave EEG bursts. Under anesthesia, adult homozygous tottering mice were implanted with permanent epidural electrodes, and at least 7 days elapsed before electrocorticograms in unrestrained mice were scored for seizure incidence and duration. Caffeine (5, 10, 15 mg/kg, n = 8) injected intraperitoneally (i.p.) at the fourth hour of 8-h recording sessions significantly (p less than 0.001 for 10 and 15 mg) decreased seizure incidence as compared with control saline injections. Spike and wave bursts were eliminated during the 30 min after injection and reached 50% preinjection levels between the first and the second hour after injection. Another central nervous system (CNS) stimulating drug, amphetamine (1 mg/kg; n = 5), under identical conditions failed to decrease seizure incidence in this mutant. PMID- 3113929 TI - An overview of pediatric seizure disorders and epileptic syndromes. AB - Seizures are common in infants and children and must be differentiated from a wide variety of other neurological and nonneurological disorders which include episodic disturbances of behavior. If the diagnosis is clear, then one must decide if the seizure is an isolated event and unlikely to recur (as are many afebrile generalized convulsive seizures in early childhood), a symptom of underlying cerebral pathology, or part of an epileptic syndrome. The latter may be a potentially lethal neurodegenerative disease or a benign epilepsy with excellent outcome. This review will discuss the various aspects of epilepsy in the pediatric age group, emphasize the benign nature of most seizures in children (including many forms of partial, or focal, seizures), and present an overview of the more serious epileptic syndromes. The myoclonic epilepsies will be used as a model to illustrate the wide scope of epileptic phenomena in infants and children. PMID- 3113930 TI - Neonatal seizures: problems in diagnosis and classification. AB - The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalographic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction. PMID- 3113931 TI - Genetic considerations in childhood epilepsy. AB - This report reviews various lines of evidence demonstrating important genetic influences in the epilepsies, with special emphasis on childhood epilepsy. Five pertinent topics are discussed: (a) examples of dominant, recessive, and X-linked single-gene disorders known to be associated with epilepsy, (b) examples of gross chromosomal aberrations associated with epilepsy, (c) discussion of multifactorial and polygenic inheritance and issues of genetic heterogeneity with specific reference to idiopathic generalized epilepsy, febrile seizures, and infantile spasms, (d) brief review of experimental clues to possible pathogenetic mechanisms underlying genetic forms of epilepsy, and (e) an overview of strategies for applying genetic linkage analysis to hereditary epileptic disorders. PMID- 3113932 TI - Results of in vitro and in vivo genetic toxicity tests on methyl isocyanate. AB - Methyl isocyanate (MIC) was tested for genetic toxicity in a variety of in vitro and in vivo assays. Negative results were obtained in the Salmonella/mammalian microsome assay using five bacterial strains in a preincubation protocol. The Drosophila sex-linked recessive lethal test also gave negative results in studies that involved three routes of administration: inhalation, feeding, and injection. Positive results were obtained for three endpoints in cultured mammalian cells. Reproducible, dose-related increases in trifluorothymidine-resistant clones were induced in L5178Y mouse lymphoma cells, and the frequencies of both SCE and chromosomal aberrations increased in Chinese hamster ovary cells. These effects were independent of exogenous metabolism. In mice exposed to methyl isocyanate by inhalation, cytogenetic analyses were carried out on bone marrow, blood, and lung cells. A single, 2-hr exposure to concentrations of 0, 3, 10, and 30 ppm MIC produced no evidence of chromosomal effects in the bone marrow, although significant cell cycle delay was observed. In four experiments involving exposures on 4 consecutive days to 0, 1, 3, or 6 ppm, delays in bone marrow cell cycle were again observed. Increases in SCE and chromosomal aberrations were observed in bone marrow cells, and a dose-related increase in SCE occurred in lung cells but not in peripheral blood lymphocytes. A significant increase in micronucleated polychromatic erythrocytes in the peripheral blood was observed in male mice in one experiment. From these results, it appears that methyl isocyanate has the capacity to affect chromosome structure but not to induce gene mutations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113933 TI - Teratological research using in vitro systems. IV. Cells in culture. AB - Several in vitro cellular systems designed to screen agents for teratogenic potential are described in this report. These assays were selected from a review of literature published through the spring of 1986 that generated over 100 references on teratological research using cell-based systems. Some of the assays have a broader application than others, but most require confirmation by one or more additional complementary tests because of the specificity of the teratogenic mechanism the assays are investigating. Included are systems that use analysis of tumor cell attachment; intercellular communication; growth of human embryonic palatal mesenchyme cells; progesterone production in porcine granulosa cells; differentiation of embryonic neural crest, limb bud, midbrain, and Drosophila cells; and differentiation of tumor cells. Because of the dynamic nature of cell culture work, the group of assays listed here should not be viewed as encompassing all cell systems of value with regard to teratogenicity testing; instead, the list represents several of the more prominent systems now being evaluated by the scientific community. PMID- 3113935 TI - Arterial blood PO2 and PCO2 in horses during early halothane-oxygen anaesthesia. AB - Arterial blood was collected from 25 clinically normal horses immediately before and serially throughout the first hour of halothane oxygen anaesthesia. Blood was analysed for oxygen and carbon dioxide partial pressure (PaO2, PaCO2). Measurements of inspired oxygen concentration during anaesthesia permitted direct correlation with blood gases. Horses were divided arbitrarily into two groups based on their age: two to seven years, n = 15; over seven years, n = 10. Average (+/- sd) PaO2 and PaCO2 was 14.1 +/- 1.5 kPa (106 +/- 11 mmHg) and 5.9 +/- 0.6 kPa (44.4 +/- 4.4 mmHg) respectively in conscious, young horses and 14.0 +/- 0.7 and 5.8 +/- 0.5 kPa (105 +/- 5 and 43.3 +/- 3.8 mmHg) respectively in conscious older horses. Arterial oxygen tension decreased to 9.3 +/- 1.0 and 8.5 +/- 1.4 kPa (69.6 +/- 7.8 and 63.7 +/- 10.4 mmHg) in young and older air breathing horses respectively immediately following intravenous anaesthetic induction, recumbency and orotracheal intubation. At this time, PaCO2 was 6.5 +/- 0.5 and 6.0 +/- 0.7 kPa (48.7 +/- 3.5 and 45.1 +/- 4.9 mmHg) respectively. By 30 mins after the start of halothane in oxygen (6 litres/min) anaesthesia PaO2 increased to a maximum in both study groups. Arterial PCO2 increased steadily during anaesthesia and 60 mins after induction PaCO2 was 10.5 +/- 2.4 kPa (78.5 +/- 17.8 mmHg) in the younger horses and 9.2 +/- 1.6 kPa (68.8 +/- 11.8 mmHg) in the older horses. During inhalation anaesthesia PaO2 tended to be greater at comparable time periods in the younger horses despite a slightly greater degree of hypoventilation. PMID- 3113934 TI - Teratological research using in vitro systems. V. Nonmammalian model systems. AB - In this review of alternative tests to whole-animal rodent studies, the use of sub-mammalian and sub-vertebrate systems is investigated. The history, methodology, known limitations, end points, dose response, and requirements of virus, hydra, planarian, cricket, fish, amphibia, Drosophila, and chicken embryo systems are discussed. PMID- 3113936 TI - Dietary composition and acid-base status: limiting factors in the performance of maximal exercise in man? AB - Seven healthy male subjects exercised to exhaustion at a workload equivalent to 100% of their maximal oxygen uptake (VO2max) on 3 separate occasions. Each high intensity exercise test was performed on an electrically braked cycle ergometer; the first took place after a normal diet (46 +/- 8% carbohydrate (CHO), 41 +/- 7% fat and 13 +/- 3% protein); the second after 3 days of a low CHO diet (7 +/- 3% CHO, 64 +/- 5% fat and 29 +/- 4% protein) and the third after 3 days of a high CHO diet (76 +/- 6% CHO, 14 +/- 5% fat and 10 +/- 2% protein). Acid-base status and selected metabolites were measured on arterialized venous blood at rest prior to exercise and during the post-exercise period. Plasma urea concentration and urine total acidity were measured on each day of the experiment. Exercise time to exhaustion was longer after the normal (p less than 0.05) and high (p less than 0.01) CHO diets compared with the low CHO diet. Pre-exercise plasma bicarbonate concentration and blood PCO2 were higher after the high CHO diet when compared with the normal (p = 0.05, p less than 0.05 respectively) and low CHO conditions (p less than 0.05, p less than 0.05 respectively). Pre-exercise bicarbonate was also higher after the normal CHO diet when compared with the low CHO diet (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113937 TI - Bacterial interference by anaerobic species isolated from human feces. AB - Eighty-four anaerobic fecal isolates obtained from five healthy volunteers were tested for their ability to inhibit in vitro growth of eight species of Enterobacteriaceae, four species of faculative gram-positive cocci, and Pseudomonas aeruginosa. Forty-nine of the 84 anaerobic isolates (58%) inhibited the growth of at least one indicator bacterium. Isolates of Bacteroides and Bifidobacterium spp. were most consistently inhibitory. Anaerobic cocci and clostridia were infrequently inhibitory; eubacteria showed no inhibitory activity. Serratia marcescens was the indicator most often inhibited; 54% of all anaerobic isolates tested, all of nine Bifidobacterium isolates and 33 of 43 Bacteroides isolates inhibited this organism. No anaerobes inhibited the growth of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter freundii, Citrobacter diversus or Streptococcus faecalis. PMID- 3113938 TI - Post-antibiotic effect of ciprofloxacin on Pseudomonas aeruginosa. AB - The post-antibiotic effect of ciprofloxacin on five strains of Pseudomonas aeruginosa was examined. Ciprofloxacin demonstrated rapid bactericidal action at concentrations achievable in serum. After removal of the drug persistent suppression of bacterial growth followed by regrowth was observed for all strains after exposure of the organisms to various concentrations of ciprofloxacin for limited periods of time (0.25-3 h). The duration of this post-antibiotic effect increased with the concentration of the drug and duration of exposure up to a point of maximal response. This point was reached after approximately 2.2 h using a ciprofloxacin concentration 5-10 times the MIC and 1-2 h of treatment. PMID- 3113939 TI - Value of isotypic characterization of antibodies to Echinococcus granulosus by enzyme-linked immuno-filtration assay. AB - In order to establish prognostic criteria for patients with hydatid cysts and to identify functional antigenic components of Echinococcus granulosus 87 sera from 36 patients were studied by enzyme-linked immuno-filtration assay (ELIFA) to characterize the four main classes of specific immunoglobulins and to determine compared immunological profiles (CIP) between samples or subjects. This method uses filtration with labelled antibodies to reveal precipitating systems preformed by immuno-electro-diffusion on cellulose acetate strips. IgG antibodies were demonstrated in the arc 5 and in 11 others bands. Specific IgA, IgE and IgM to Echinococcus granulosus was found in 19%, 53% and 69% respectively of patients with hydatids. The presence of IgM and/or IgE antibodies one year after treatment always correlated with disease. Specific IgA was detected more often in patients with pulmonary cysts. Pre- and post-operative monitoring by CIP-ELIFA proved simple and rapid to perform and of decided prognostic value. Two antigens, corresponding to arc 5 and arc X, were frequently associated with the poly isotypic immune response. PMID- 3113940 TI - Importance of carbenicillin and gentamicin cross-resistant serotype 0:12 Pseudomonas aeruginosa in six Athens hospitals. AB - One hundred and six clinical isolates of Pseudomonas aeruginosa, collected from various hospitals were typed with O-antisera and studied for their susceptibility to antibiotics and phages. Forty-four of 49 multiresistant isolates belonged to the O12 serogroup, a serogroup rarely found among strains of other resistance phenotypes. Eleven of the 45, O12 isolates were resistant to all phages, and 31 were sensitive only to phage 68. The latter pattern was encountered in nine of the 61 strains comprising the other O-serogroups. PMID- 3113941 TI - In vitro susceptibility of Neisseria gonorrhoeae to RO 23-6240 and ciprofloxacin. PMID- 3113942 TI - In vitro activity of new antimicrobial agents against Pseudomonas aeruginosa isolates from cystic fibrosis patients. PMID- 3113943 TI - Lack of cross-resistance between imipenem and other beta-lactam antibiotics for Pseudomonas aeruginosa. PMID- 3113944 TI - Towards a global perspective of nosocomial infections. PMID- 3113945 TI - Crystallization of and X-ray investigations on glucose dehydrogenase from Bacillus megaterium. AB - The tetrameric glucose dehydrogenase from Bacillus megaterium M1286 belongs to the 'short' family of dehydrogenases with 262 amino acids per subunit (Mr approximately 30,000), and does not require Zn2+ for enzymatic action. It was crystallized as complex with its coenzyme NAD from a 1-2% protein solution by the batch method using ammonium sulfate as precipitant at pH 6.5. Crystals appeared within two days as clusters of large plates with maximum dimensions of 2 mm, which diffract X-rays to a resolution of at least 0.2 nm. The space group is orthorhombic P2(1)2(1)2(1), unit-cell dimensions are a = 15.03 nm, b = 10.42 nm and c = 6.74 nm. Assuming one molecule (approximately 120 kDa) per asymmetric unit the VM value is 0.0022 nm3/Da and the solvent content of the crystals is 45% based on a partial specific volume for the protein of 0.723 ml/g. The crystallization was further improved by using the microdialysis technique where instead of clusters, single crystals appeared within 7 days. PMID- 3113946 TI - Structure of the major triglycosyl phenol-phthiocerol of Mycobacterium tuberculosis (strain Canetti). AB - Phenol-phthiocerol glycolipids have been found previously in Mycobacterium leprae, M. kansasii, M. bovis and M. marinum, but not in M. tuberculosis. A search for glycolipids in this latter species showed that the Canetti strains of M. tuberculosis synthesize a major triglycosyl phenol-phthiocerol, accompanied by minor amounts of other glycolipids with a similar aglycone moiety. The triglycoside moiety has the following structure: 2,3,4-tri-O-methyl L fucopyranosyl(alpha 1----3)L-rhamnopyranosyl(alpha 1----3)2-O-methyl L rhamnopyranosyl(alpha 1-. The aglycone moiety consists in phenol-phthiocerol (two homologs). Its two secondary alcohol functions are esterified by mycocerosic acids (homologs with 26-32 carbon atoms and with 2-4 methyl branches). The proposed structure differs on several points from the M. leprae glycolipids, but presents some analogy with the major glycolipid of M. kansasii. A minor monoglycosyl phenol-phthiocerol was also studied. Its overall structure is very similar to that of M. bovis, with 2-O-methyl rhamnose as sugar moiety. PMID- 3113947 TI - Sequential processing reactions in the formation of hormone amides. AB - The substrate specificity of an enzyme with amidating activity, present in porcine pituitary, was investigated by examining its ability to convert the synthetic peptides D-Tyr-Val-Gly and D-Tyr-Val-Gly-Lys-Arg to the dipeptide amide D-Tyr-Val-CONH2. The purified enzyme catalysed the amidation reaction with the tripeptide but did not accept the pentapeptide as a substrate. With the mixture of enzymes present in a membrane fraction from porcine pituitary or the enzymes in a secretory granule fraction, both the tripeptide and pentapeptide substrates gave rise to D-Tyr-Val amide; the formation of dipeptide amide from the pentapeptide, however, involved a latency period after which amidation occurred at a similar rate with the two substrates. Evidence was obtained that arginine and lysine were released from the C terminus of the pentapeptide before amidation took place since the rate of formation of dipeptide amide was reduced at pH values that were compatible with amidation but unfavourable to the action of carboxypeptidase H. In addition formation of the dipeptide amide from the pentapeptide was blocked by guanidinoethylmercaptosuccinic acid and glycylarginine, which are inhibitors of carboxypeptidase enzymes. The experiments demonstrate that removal of basic residues from the C terminus of a peptide and amidation at C-terminal glycine are reactions that take place consecutively. These prohormone-processing reactions, which are intrinsic to the formation of hormone amides, did not synergise. PMID- 3113948 TI - Prenol nomenclature. Recommendations 1986. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). PMID- 3113949 TI - Characterization of a polysaccharide component of lipopolysaccharide from Pseudomonas aeruginosa IID 1008 (ATCC 27584) as D-rhamnan. AB - Structural studies were carried out on a rhamnose-rich polysaccharide isolated from the O-polysaccharide fraction of lipopolysaccharide in Pseudomonas aeruginosa IID 1008 (ATCC 27584) after destruction of the major O-specific chain by alkaline treatment. The isolated polysaccharide contained rhamnose, 3-O-methyl 6-deoxyhexose, glucose, xylose, alanine, galactosamine and phosphorus in a molar ratio of 67:6.9:4.3:2.1:1.1:1.0:4.1. Data from analysis involving Smith degradation, methylation, 1H-NMR spectroscopy and optical rotation measurement showed that the polysaccharide was built up of three moieties, a rhamnan chain composed of about 70 D-rhamnose residues, the core chain and an oligosaccharide chain comprising 3-O-methyl-6-deoxyhexose, xylose, rhamnose and probably glucose. The repeating unit of the rhamnan chain was indicated to have the following structure:----3)D-Rha(alpha 1----3)D-Rha(alpha 1----2)D-Rha(alpha 1----. This structure is identical with that proposed previously for the repeating unit of the side chain of lipopolysaccharide from plant pathogenic bacteria Pseudomonas syringae pv. morsprunorum C28 [Smith, A.R.W., Zamze, S.E., Munro, S.M., Carter, K. J. and Hignett, R.C. (1985) Eur. J. Biochem. 149, 73-78]. PMID- 3113950 TI - Purification and characterization of the spoOA protein of Bacillus subtilis from an overproducing strain of Escherichia coli. AB - The spoOA gene of Bacillus subtilis is essential for the earliest stage of sporulation. To purify and characterize the product of the spoOA gene, we constructed a fusion plasmid in which the spoOA coding region was placed under the control of the Ptac promoter. When expression of the spoOA gene was induced in Escherichia coli cells by derepression of Ptac, the SpoOA protein constituted 15% of total cellular protein. The SpoOA protein was purified to homogeneity from these cells. We found that the NH2-terminal amino acid sequence of the purified protein was essentially the same as that of the SpoOA protein (spoOA-cat protein) from B. subtilis, and that the NH2-terminal methionine of the SpoOA protein from E. coli was formylated presumably because of insufficient amounts of the deformylating enzyme. The T signal [Ganoza, M. C., Marliere, P., Kofoid, E. C. and Louis, B. G. (1985) Proc. Natl Acad. Sci. USA 82, 4587-4591], in addition to the Shine-Dalgarno signal to determine the initiation codon of the spoOA gene, is considered to function in E. coli as well as in B. subtilis. We also found that the purified SpoOA protein had a DNA-binding activity. It was preferentially bound to the 175-bp BclI fragment of phi 105 DNA, and was released in the presence of 0.3 M KCl. PMID- 3113951 TI - The effect of thrombin on the complex between factor VIII and von Willebrand factor. AB - Purified human factor FVIII (FVIII; 6000-8000 U/mg) was radiolabeled and bound to immobilized von Willebrand factor (vWF). The complex was incubated with human thrombin. Thrombin induced a release of 65% of the radioactivity initially bound. Released FVIII fragments and fragments remaining bound during incubation with thrombin were analyzed using gel electrophoresis. This led to the following observations. Released fragments largely consisted of Mr-70000 and Mr-50000 fragments; Mr-90000 and Mr-80000 fragments were only found in the fractions remaining bound to vWF and decreased with time. In contrast to these digestion products of FVIII, the Mr-42000 heavy-chain fragment remained bound to vWF, comprising the larger part of the radioactivity after a 2-h incubation. No thrombin-induced cleavages were observed in vWF. Furthermore, vWF-coated wells preincubated with thrombin were still able to bind 125I-FVIII. These results implicate a new concept for the activation of vWF-bound FVIII. Activation is a multistep process in which several cleavages are necessary to produce and release a coagulant-active FVIII molecule (FVIIIa), which is probably an Mr-50000/70000 heterodimer. Inactivation of FVIIIa is likely to be the result of a nonproteolytic dissociation due to loss of the joining divalent cation(s). PMID- 3113952 TI - Comparison of the sex and subcellular distributions, catalytic and immunochemical reactivities of hepatic epoxide hydrolases in seven mammalian species. AB - Sex and species differences in hepatic epoxide hydrolase activities towards cis- and trans-stilbene oxide were examined in common laboratory animals, as well as in monkey and man. In general trans-stilbene oxide was found to be a good substrate for epoxide hydrolase activity in cytosolic fractions, whereas the cis isomer was selectively hydrated by the microsomal fraction (with the exception of man, where the cytosol also hydrated this isomer efficiently). The specific cytosolic epoxide hydrolase activity was highest in mouse, followed by hamster and rabbit. Epoxide hydrolase activity in the crude 'mitochondrial' fraction towards trans-stilbene oxide was also highest in mouse and low in all other species examined. Microsomal epoxide hydrolase activity was highest in monkey, followed by guinea pig, human and rabbit, which all had similar activities. Sex differences were generally small, but where significant, male animals had higher catalytic activities than females of the same species in most cases. Antibodies raised against microsomal epoxide hydrolase purified from rat liver reacted with microsomes from all species investigated, indicating structural conservation of this protein. Antibodies directed towards cytosolic epoxide hydrolase purified from mouse liver reacted only with liver cytosol from mouse and hamster and with the 'mitochondrial' fraction from mouse in immunodiffusion experiments. Immunoblotting also revealed reaction with rat liver cytosol. The cytosolic and 'mitochondrial' epoxide hydrolases in all three mouse strains and in both sexes for each strain were immunochemically identical. The anomalies in human liver epoxide hydrolase activities observed here indicate that no single common laboratory animal is a good model for man with regard to these activities. PMID- 3113953 TI - Structural and immunochemical characterization of a ribosomal protein from gram positive Micrococcus luteus which is functionally homologous to Escherichia coli ribosomal protein S1. AB - Ribosomes from gram-positive Micrococcus luteus contain an acidic protein (ML S1). ML-S1 has been purified by chromatography of ribosomes on a poly(U) Sepharose column and the purified protein has a mobility in sodium dodecyl sulphate/polyacrylamide gels similar to that of ribosomal protein S1 of Escherichia coli (apparent Mr 72,000). Protein ML-S1 reacted with E. coli anti-S1 serum with an immunological partial-identity reaction. ML-S1 also reacted with antibodies raised against two structural domains of E. coli S1 (the N-terminal ribosome-binding domain and central and C-terminal nucleic-acid-binding domain). Weak reaction with antiserum to the nucleic-acid-binding domain of E. coli S1 was observed. ML-S1 was digested with trypsin under mild and exhaustive conditions. Mild digestion resulted in the production of a trypsin-resistant core (ML-S1F1) like E. coli S1. The fragment pattern obtained after exhaustive digestion differed appreciably from that obtained with E. coli S1. ML-S1 bound to poly(U) as strongly as E. coli S1 and also showed appreciable binding to denatured DNA. Addition of ML-S1 to S1-depleted ribosomes from E. coli and M. luteus markedly stimulated the poly(U)-directed polyphenylalanine synthesis. Phage MS2-RNA dependent translation was also found to be stimulated by ML-S1 although to a much lesser extent than the stimulation by E. coli S1. At a molar excess of ML-S1 to ribosomes the protein showed a similar inhibitory effect to E. coli S1 on polypeptide synthesis. Our data indicate that ML-S1 retained the structural domains important for its function despite certain structural differences from E. coli S1. PMID- 3113954 TI - A new type of substratum adhesion structure in NRK cells revealed by correlated interference reflection and electron microscopy. AB - The substratum adherent membrane of NRK cells in vitro has been studied using correlated interference reflection and surface replica electron microscopy. Structures visualized by interference reflection microscopy were identified in the subsequently prepared platinum-carbon replicas of the adherent membranes. Substratum adherent membranes were prepared using a hypotonic shock/cell shearing technique (lysis-squirting). Typically 20% of the original ventral membrane surface area and 50% of the original focal adhesion number were retained. Microfilament bundle termini, clathrin-coated sheets and pits, cytotic vesicles having a ridged surface and groups of membrane associated particles were well preserved in the replicas. Two types of isolated adhesion structures were found after lysis-squirting. In addition to typical elongate focal adhesions containing actin and vinculin, we report the existence of adherent membrane patches lacking microfilament bundles and negative for vinculin labelling, but coated with clathrin and identifiable in interference reflection microscopy as less dark than focal adhesions and having dot, U- or sinusoidal shapes. PMID- 3113955 TI - Cell distribution and antigenic properties of mammalian sarcolectins. AB - Sarcolectins are present in a great variety of tissues from mammalian origin. Such substances were observed to be secreted from cultures of human embryonic fibroblasts, human osteosarcoma and rat Rous sarcoma transformed cells and could be extracted from TG 180 Crocker Sarcoma or normal human placenta. All sarcolectins tested here, were comparable by their physicochemical properties to those previously reported in hamster or human sarcomas. Indeed, they are proteins or glycoproteins, resistant to pepsin and migrate in SDS-PAGE in the 65 kDa area. They agglutinate cells with an affinity for simple sugars and degrade previously established interferon-induced antiviral resistance. Considering the hamster sarcolectin as reference in this comparative study, both differences and similarities in the antigenic properties of mouse, rat and human sarcolectin variants were demonstrated. An indirect immunofluorescence assay showed that sarcolectins were specifically labelled on the cell surface but not detected in the cytoplasm after methanol or acetone permeabilization of the membrane. By electron microscopy, using immunoperoxidase labelling, sarcolectins can be localized on the surface of normal, transformed, human or rat cells. Only limited segments of normal cell membranes were labelled, while transformed cells were frequently stained on their whole surface. Other known extracellular proteins, such as fibronectin and collagen, did not share common antigenic determinants with sarcolectins. PMID- 3113956 TI - Glutaraldehyde-fixed transformed and non-transformed cells induce contact dependent inhibition of growth in non-transformed C3H/10T1/2 mouse fibroblasts, but not in 3-methylcholanthrene-transformed cells. AB - C3H/10T1/2 mouse fibroblasts showed a pronounced inhibition of growth when reaching a critical cell density. The situation of high cell density could be mimicked by the addition of glutaraldehyde-fixed cells to sparsely seeded proliferating cells. Treatment of the C3H/10T1/2 cells with 3-methylcholanthrene led to a high frequency of piled up foci (118 type II and type III foci in 78 cultures). Cells of a type III focus of a treated culture were cloned. These cells grew in soft-agar and reached 10 times higher cell densities when grown in culture dishes, than did their non-transformed counterparts. Glutaraldehyde-fixed transformed cells did not differ from fixed non-transformed cells in the ability to inhibit the growth of sparsely seeded non-transformed cells. On the other hand, both the addition of fixed normal or transformed C3H/10T1/2 cells did not affect the growth rate of transformed cells. In a concept explaining the density dependent inhibition of growth of non-transformed cells by a specific interaction of plasma membrane-localized effectors with plasma membrane-localized receptors, the present findings would indicate that the transformed cells used express active effectors but are functionally defective in the receptors or in the signal transmission. PMID- 3113957 TI - Haemodynamic effects of metoprolol and intravenous nitroglycerin versus metoprolol alone in patients with acute myocardial infarction. AB - Among the various treatments adopted to protect the acutely ischaemic myocardium, favourable results have been reported for beta-blockers. Nitrates can also reasonably be expected to exert favourable effects in acute myocardial infarction considering their haemodynamic action. In this study we compared the haemodynamic effect of metoprolol alone with the effect of metoprolol plus nitroglycerin. Fourteen patients, admitted within 12 hours from the clinical onset of acute myocardial infarction, were initially given intravenous metoprolol (5 + 5 + 5 mg) followed 15 minutes later by an additional 50 mg oral dose. Thereafter, they were randomly allocated to a treatment with metoprolol alone (Group 1) or metoprolol plus intravenous nitroglycerin (Group 2). The two groups were comparable with regard to age, sex, time to admission, time to therapy, site of necrosis, Killip class, and infarct size. Acute beta-blockade induced a marked decrease of cardiac output, systolic blood pressure and heart rate along with a small increase of pulmonary wedge pressure and a marked systemic vasoconstriction. In Group 1 patients these haemodynamic changes persisted up to twelve hours after randomization; in Group 2 patients the addition of nitroglycerin induced a prompt decrease of pulmonary wedge pressure and peripheral vascular resistance whereas the double product was unchanged. In conclusion, intravenous nitroglycerin induces a beneficial haemodynamic effect after early beta-blockade with metoprolol. PMID- 3113958 TI - His bundle tachycardia--arrhythmogenic and antiarrhythmic effects of therapy. AB - His bundle tachycardia is a rare arrhythmia in infants and children and is resistant to therapy. There is now sufficient evidence from reported cases and a further patient reported below to suggest that drug management of this arrhythmia is a reasonable alternative to His bundle ablation with life-long pacing from infancy. PMID- 3113959 TI - Intestinal accumulation of 111In-granulocytes in patients studied because of occult infection. AB - 111In-granulocyte scintigraphy was performed on 245 patients in whom a localized infection was suspected. In 123 patients scintigraphy was positive and of these 35 (28%) had intestinal accumulations of 111In-granulocytes. Specific local causes for the intestinal uptake of radioactivity were antibiotic associated colitis (eight patients), local pyogenic bowel infection (four patients), systemic disease (two patients), bowel necrosis (two patients), colonic cancer (one patient) and Stevens-Johnson's syndrome (one patient). Nonspecific mechanisms of bowel accumulation were desquamation of labelled granulocytes (12 patients) and bleeding (two patients). In three cases the mechanism of colonic accumulation of granulocytes was not revealed. These results show that unexpected accumulations of labelled granulocytes in the gut is not a rare phenomenon and is often due to clinically significant intestinal inflammation or other disease, especially in patients who do not have signs of respiratory, pancreatic or oesophageal inflammation causing desquamated granulocytes to accumulate in the gut. PMID- 3113960 TI - Effect of hypocapnia on cerebral oxygen metabolism and blood flow in ischemic cerebrovascular disorders. AB - Effects of hypocapnia on cerebral oxygen consumption (CMRO2) and blood flow (CBF) in cerebral ischemia were studied in 19 patients. The CMRO2 did not change significantly during hypocapnia within the whole group of patients, because 10 out of 19 cases showed a decrease (p less than 0.001) and other 9 showed an increase (p less than 0.01) of CMRO2 during hypocapnia. The first 10 showed higher resting CMRO2 (p less than 0.001) and arteriovenous differences of oxygen content (AVDO2; p less than 0.02) than the other 9. However, the resting CBF and CO2 reactivity to hypocapnia were not different between them, and clinical situations were also similar. A dissociation between flow and metabolism was suggested in the first 10 with rather preserved CMRO2, while reduced metabolic demands were suggested in the other 9. Different responses of CMRO2 to hypocapnia are expected in cerebral ischemia, i.e. in cases with rather preserved CMRO2 it decreases despite an AVDO2 increase, suggesting a capability of CMRO2 to respond to CBF reduction, while it increases in cases with more decreased CMRO2, as the AVDO2 increase exceeds the CBF reduction to maintain the decreased CMRO2 for a further CBF reduction. The vascular CO2 reactivity, therefore, might be maintained to be constant between these patients. PMID- 3113961 TI - Cerebrospinal fluid lactate in patients with hepatic encephalopathy. AB - Cerebrospinal fluid (CSF) lactate and pyruvate concentrations were determined in 16 patients with hepatic encephalopathy before and/or after treatment. CSF lactate was significantly increased to 1.92 +/- 0.11 mmol/l in hepatic encephalopathy before the treatment in comparison to 1.40 +/- 0.05 mmol/l in control subjects. In 9 of 11 patients with moderate or stage 2 encephalopathy, CSF lactate levels were below 2 mmol/l. In contrast, in 4 of 5 patients with stage 3-4 encephalopathy, CSF lactate levels were higher than 2 mmol/l. CSF lactate was decreased with the recovery of neurological symptoms by the treatment. These findings indicate that CSF lactate levels reflect the severity of metabolic impairment of the brain. Hypocapnia was frequently observed in these encephalopathic patients, and arterial PCO2 correlated inversely with CSF lactate and linearly with CSF HCO3-, suggesting that CSF lactic acidosis contributes to hyperventilation in hepatic encephalopathy. It is concluded from present results that metabolic disorder of neuronal cells might be one of the important factors for the development of hepatic encephalopathy. PMID- 3113962 TI - The role of non-steroidal anti-inflammatory drugs in sports injuries. AB - The running population in the United States is estimated to be more than 60 million, and two out of every three of these runners will seek medical attention because of injuries. The cause of lower extremity injuries is the impulsive impact that occurs on foot strike. At 800 foot strikes per mile, a 150-pound runner will be subjected to forces of 120 tons per foot per mile. The use of the non-steroidal anti-inflammatory drugs (NSAIDs) in runners has become widespread. This is especially true in the case of marathon runners who use NSAIDs like piroxicam to relieve their overuse pains so they can continue to run with injuries, although this use is not advocated. NSAIDs do, however, play a role in treating many running injuries and can help the runner return to his chosen sport. PMID- 3113963 TI - Seeking clues for a positive diagnosis of the irritable bowel syndrome. AB - Despite its high prevalence the irritable bowel syndrome (IBS) lacks acceptable pathophysiological markers and its diagnosis largely depends on the exclusion of underlying organic disease. Systemic acid-base balance, serum electrolytes and the composition of faecal water (electrolytes and organic anions), were studied in thirty-eight diarrhoeal patients out of a series of ninety-three consecutive IBS patients. Only patients with diarrhoea as the predominant symptom were included in the study to evaluate whether this subgroup could provide the clue for a positive diagnosis of the syndrome. Serum electrolytes and systemic acid base balance were within the normal range. Faecal electrolytes were also normal (Na 26.6 +/- 19.3 SD; K 66.8 +/- 28.3; Cl 19.1 +/- 15.2 mEq 1(-1)), despite the finding of a moderately increased 24-h faecal output. The K:Na ratio was also within the normal range. These data are in agreement with the lack of systemic changes observed in IBS patients even with profuse or longstanding diarrhoea. Both faecal short chain fatty acids and lactic acid were increased in patients vs. controls, but a considerable overlap with normal values was observed (131.4 +/- 62.6 SD vs. 108.5 +/- 58.3 mEq 1(-1). Only lactic acid concentration was significantly higher than in controls (1.3 +/- 1.2 vs. 0.5 +/- 0.2). Despite these findings it is concluded that the subgroup of IBS patients with diarrhoea also appears to lack a pathophysiological marker and does not provide clues for a positive diagnosis of this syndrome. PMID- 3113964 TI - Increased DNA synthesis in adipocytes and capillary endothelium in rat adipose tissue during overfeeding. AB - Adult male rats were subjected to overfeeding with a high-fat, high-sugar diet for 3 and 7 days resulting in a moderate expansion of adipose tissue depots by an increase in fat-cell size. Seventeen hours and 7 days after injection of a pulse of labelled thymidine, specific activity of DNA was examined in different cellular fractions obtained from the epididymal and perirenal adipose tissues after collagenase liberation and separation procedures. A slow increase of formation of new adipocytes occurred after 3 and 7 days of overfeeding, most pronounced in cells from perirenal adipose tissue. Capillary endothelium and cells in the stromal fraction showed a rapid synthesis and turn-over. Overfeeding induced an increased formation of new capillary endothelial cells after 7 days of overfeeding, again most pronounced in perirenal cells. It was concluded that new fat cells are formed at a slow rate early during overfeeding. Capillary endothelium in adipose tissue has a high rate of turnover, and its synthesis is increased further by overfeeding. New adipocytes precede, and possibly stimulate, the formation of new capillaries. Formation of new cells in the remaining stromal vascular cells is probably occurring at different rates among different types of cells. PMID- 3113965 TI - Dihydralazine induces marked cerebral vasodilation in man. AB - Dihydralazine is widely used for acute control of hypertension. In experimental studies it seems to dilate cerebral resistance vessels and increase intracranial pressure. However, the effect on cerebral blood flow (CBF) in man has been little studied. Measurements of CBF were performed with the i.v. xenon-133 technique in seven young, normotensive volunteers before and 15, 60 and 180 min after 6.25 mg i.v. dihydralazine, corresponding approximately to 0.1 mg kg-1 body weight. For comparison the CBF reactivity to inhalation of 5% CO2 in air was investigated. Dihydralazine increased CBF throughout the period of study, in median 16, 27 and 23% at the three periods of measurements, respectively. The arterial blood pressure remained unchanged, whereas heart rate increased significantly. During CO2 inhalation, CBF increased on average 29%. Thus, the cerebral vasodilation exerted by a small i.v. dose of dihydralazine was of the same order of magnitude as the effect of 5% CO2 inhalation. These results in normal subjects should be extrapolated to diseased persons only with extreme caution. Still, the very marked and long lasting vasodilation observed suggests that dihydralazine, from a theoretical point of view, in certain clinical situations may be harmful. PMID- 3113966 TI - Studies on collagen metabolism in the Marfan syndrome. AB - The pattern of collagen metabolism was studied in nine fibroblast cultures from Marfan patients. The cellular synthesis of collagen and non-collagenous proteins was significantly increased, whereas secretion and degradation remained unchanged. Other steps of post-translational processing such as hydroxylation of prolyl or lysyl residues, affecting triple helix stability, were found to be normal. Furthermore, peptide mapping of isolated a 1(I), a 2(I) and a 1(III) gave no evidence for structural defects. Hence, our study would support the notion that defects other than those affecting collagen type I or III metabolism must represent the molecular basis of the Marfan syndrome. PMID- 3113967 TI - Bactericidal capacity against Neisseria meningitidis of normal human serum and sera with functional deficiencies of the third and eight complement factor. AB - The bactericidal capacity of serum with C3 deficiency secondary to circulating C3 nephritic factor, serum with C8 deficiency and normal human serum were assessed in vitro against Neisseria meningitidis groups A-C. Normal human serum and C8 deficient serum, originating from a 28-year-old male with two episodes of meningococcal meningitis, showed significant bactericidal capacity against meningococci groups A and B. Against group C meningococci the C8-deficient serum revealed significant bactericidal capacity, whereas normal human serum showed no bactericidal effect. Serum with C3 deficiency, obtained from a 16-year-old female with two episodes of meningococaemia, showed no bactericial effect against meningococci groups A-C. Incubation of normal human serum and C8-deficient serum with isolated nephritic factor resulted in C3 depletion and abolished the bactericidal effect. PMID- 3113968 TI - Normal pathways for glucuronidation, sulphation and oxidation of paracetamol in Gilbert's syndrome. AB - A group of eleven subjects with Gilbert's syndrome was characterized by conventional tests and determination of bilirubin and its conjugates in plasma by alkaline methanolysis and thin layer chromatography. After a 1 g dose of paracetamol h.s. the drug and its metabolites were measured by high performance liquid chromatography (HPLC) in the overnight 8-h urine sample. The amounts of paracetamol and of its metabolites recovered in urine were almost identical with those found in the control group (n = 10). The glucuronide:paracetamol ratio, which is considered to be an index of glucuronidation, was not correlated with the fraction of bilirubin present in plasma as glucuronides. These data do not suggest that in subjects with Gilbert's syndrome therapeutic doses of paracetamol are associated with an increased risk for hepatic or systemic toxicity. PMID- 3113969 TI - Effect of the composition of very low and low density lipoproteins on the rate of cholesterylester transfer from high density lipoproteins in man, studied in vitro. AB - The process of cholesterylester (CE) transfer is supposed to be a regulatory factor in the distribution of CE between lipoproteins. In addition to the activity of CE transfer protein, this process may be affected by acceptor lipoprotein characteristics. In this study the effect of the composition of different very low density lipoproteins (VLDL) and low density lipoproteins (LDL) on the ability to accept CE from HDL in vitro was investigated. [3H]-CE high density lipoprotein (HDL) (100 nmol CE) from one batch was incubated with VLDL (75 nmol CE), isolated from fifteen subjects for 4 h and separately with LDL (250 nmol CE), isolated from thirteen subjects for 16 h, both in the presence of lipoprotein-free plasma providing a source of cholesterylester transfer protein. The CE transfer rate of VLDL (range 1.34-2.84% [3H]-CE transferred h-1) was correlated to the triacylglycerol (TG):CE molar ratio (r: 0.63, P less than 0.05), to the phospholipid (PL):CE molar ratio (r: 0.75, P less than 0.01), to the protein (Pr):CE ratio (expressed in g nmol-1) (r: 0.72, P less than 0.01) and to the free cholesterol (FC):CE molar ratio (r: 0.69, P less than 0.01), but not to the FC:PL molar ratio (r: -0.08, NS). The CE transfer rate to LDL (range 1.18 3.59 nmol CE h-1) was correlated to the Pr:CE ratio (r: 0.72, P less than 0.01) and inversely to the FRC:PL molar ratio (r: -0.88, P less than 0.001), but not to the TG:CE molar ratio (r: 0.40, NS), nor to the FC:CE molar ratio (r: -0.37, NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113970 TI - Quinidine reduces biliary clearance of digoxin in man. AB - Quinidine is known to reduce the renal clearance of digoxin, but this effect does not completely explain the influence of quinidine on the total clearance of digoxin. We therefore studied the effect of quinidine administration on biliary clearance of digoxin in five patients with atrial fibrillation. Biliary clearance of digoxin under steady state conditions before and during treatment with quinidine was investigated using a duodenal-marker-perfusion technique. Quinidine caused an average 42% (range 21-65%, P less than 0.02) reduction of the measured biliary clearance of digoxin. We conclude that the biliary effect adds to the previously demonstrated inhibitory effect of quinidine on the renal clearance of digoxin and helps to explain the decrease in total clearance of the drug. This is the first demonstration in man of a pharmacokinetic drug interaction at the level of biliary excretion. PMID- 3113972 TI - Highly significant negative correlations between erythrocyte aggregation value and serum concentration of high density lipoprotein cholesterol in a sample from a normal population and in patients with coronary heart disease. AB - In a previous clinical study it was found that patients with coronary heart disease and diabetics with peripheral artery disease often have an elevated erythrocyte aggregation value (AW) and that there is a positive correlation between AW and the number of risk factors found in a subject. In the present investigation we studied the relationship between AW and the serum concentration of high density lipoprotein cholesterol (HDL-C), which is known to be inversely associated with coronary heart disease (CHD) incidence. We found highly significant negative correlations between AW and HDL-C both in a subsample of the study population of a cross-sectional epidemiologic study on CHD risk factors (First Survey of the MONICA Project Augsburg) and in male patients with angiographically confirmed CHD. Correlation coefficients were -0.233 for normal men (P less than 0.01, n = 136), -0.261 for normal women (P less than 0.01, n = 117), and -0.745 for CHD patients (P less than 0.01, n = 14). The results support the concept that the erythrocyte aggregation value as an indicator of cardiovascular risk is consistent with established risk factor associations. PMID- 3113971 TI - Insulin deficiency and insulin resistance in type 2 (non-insulin-dependent) diabetes: quantitative contributions of pancreatic and peripheral responses to glucose homeostasis. AB - A non-steady state dose-response study was designed to quantitate peripheral sensitivity to insulin and pancreatic responsiveness to glucose, and to assess their relative contribution to glucose intolerance in Type 2 diabetes (Type 2 DM, non-insulin-dependent). Eleven lean and eleven obese patients with mild diabetes (fasting plasma glucose, FPG, 10.3 +/- 1.0 and 9.4 +/- 0.6 mmol l-1, respectively) were examined; twenty-six lean and twelve weight-matched obese subjects served as controls. Pancreatic response was measured by sequential injection of 0.1, 0.3 and 0.9 g kg-1 glucose; peripheral sensitivity to insulin was determined from the rate of clearance (Kgluc) of 0.3 g glucose injected sequentially together with 25, 50 and 100 mU insulin kg-1 or with 0, 12.5 and 50 mU kg-1, under somatostatin infusion. The mean dose-response curve describing glucose-induced insulin release showed increased maximal capacity to secrete insulin in obese controls, while the responses of lean as well as obese Type 2 DM were reduced by more than 80%. The mean dose-response curves relating plasma exogenous insulin levels to Kgluc were similar in lean diabetics and lean controls. The curves of both obese controls and obese diabetics were shifted to the right, demonstrating similar insulin resistance. In four lean controls, sensitivity to insulin was tested also during a hyperglycemic clamp set at 10.3 +/- 0.6 mmol l-1. Hyperglycemia reduced the Kgluc at all insulin levels. Individual dose-response curves were transformed to single weighted numerical pancreatic responsiveness scores [PRS], and peripheral sensitivity scores [PSS].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3113973 TI - A simplified dosage schedule of metrifonate in the treatment of Schistosoma haematobium infection in Somalia. AB - We have carried out an open clinical study in Somalia to evaluate the efficacy and safety of a simplified dosage schedule of metrifonate in the treatment of Schistosoma haematobium infection. The doses used were: I. 10 mg X kg-1 once daily for 3 days II. 5 mg X kg-1 thrice daily for one day III. 7.5 mg X kg-1 thrice daily for one day. We screened a total of 550 subjects in four villages for egg excretion in urine, and selected patients with more than 200 eggs per 10 ml of urine. In the initial phase of the study eight patients were assigned to each of the three dose schedules. In an extended study 38 additional patients were treated with regimen II which gave the best outcome in the initial study. Dosage Schedules I and III turned out to be toxic, and none of the patients was treated with all three doses. Adverse effects, such as abdominal colic, nausea, salivation, dizziness, and headache, were seen in almost all the patients in those two groups. Two patients from Group I reported that they fainted within 2 h after the second dose. None of the patients in Group II reported adverse effects. After 4-6 weeks follow-up, egg reduction was 96-100% for Groups I and II and the cure rate was around 60%. This study has shown that a shorter course of treatment with metrifonate might be equally effective and safer than the recommended dosage schedule with three doses of 7.5-10 mg X kg-1 fortnightly. PMID- 3113974 TI - Pharmacokinetics of human growth hormone releasing factor (hGRF-44 NH2) in normal men after intravenous administration of a large range of doses. AB - Three ranges of doses of growth hormone releasing factor (2.5-80 micrograms, 80 320 micrograms and 75-600 micrograms) were intravenously administered to healthy young volunteers in three double blind studies. Serum circulating GRF levels were determined by radioimmunoassay. Experimental concentration curves were fitted, using the extended least squares method, to a biexponential model for the structural model and power function for the variance model. The power variance model, compared to the constant variance model greatly reduced the coefficient of variation of the biexponential parameters. The power of the variance model was estimated to be 1.95. The distribution half-life was 6.6 min and the elimination half-life was 39.0 min (harmonic means). Total clearance was 0.12 +/- 0.01 microgram/l/min. No difference between these parameters was found for the various doses. GRF kinetics was linear established in the range 10 to 600 micrograms which means that elimination was not altered by the increased doses. PMID- 3113975 TI - Effect of flunarizine on pituitary secretion by healthy men and in woman with migraine. AB - Flunarizine is widely used in the prophylaxis of migraine. It is both a calcium blocker and a histamine antagonist at H1-receptors and either of these effects could alter hormonal secretion. The effect of administration of flunarizine to 8 women with common migraine on pituitary secretion has been studied. The dopamine antagonist domperidone (10 mg) and gonadotropin releasing hormone (100 micrograms) were injected iv before and after one month of flunarizine therapy (10 mg orally at bedtime). The basal prolactin level was significantly increased by the drug, and the peak induced by domperidone stimulation was reduced. Basal TSH concentrations were not affected, but the increase after domperidone was blunted. After 90 days of therapy there were no significant differences from the baseline concentration. Neither basal nor gonadotropin releasing hormone stimulated secretion of FSH and LH were affected by flunarizine. Twelve healthy men were given placebo and flunarizine (10 mg at bedtime) for 5 days in single blind fashion. Flunarizine caused a significant increase in prolactin and TSH with no effect on basal gonadotropin and thyroid hormone levels. These results can be accounted for by the calcium blocking effect of the drug, although weak interference with dopaminergic transmission is a further possibility explanation. PMID- 3113976 TI - The effect of skin allograft survival of a monoclonal antibody specific for a polymorphic CD3-like cell surface molecule in rhesus monkeys. AB - FN18, a monoclonal antibody specific for the polymorphic rhesus monkey CD3 antigen on peripheral T cells, has been tested for its immunosuppressive effect in a rhesus monkey skin graft model. Animals were injected i.v. daily with antibody and they received an allogeneic skin graft two or three days after the initial antibody treatment. All animals were carefully monitored regarding levels of the major lymphocyte subsets. In animals in which RhT3 (a CD3-like antigen) is demonstrable (i.e. FN18+ phenotype), all T cells initially disappeared from the circulation. However, T cells without RhT3 on their surface reappeared after several days, indicating that these cells must have been modulated. The survival times of the skin grafts were significantly prolonged in these animals. In monkeys in which RhT3 is not demonstrable (i.e. FN18- phenotype), mainly part of the CD4+ lymphocyte subset was depleted. Although less explicit, skin graft survival was significantly prolonged in these animals as well. In both the FN18+ and FN18- groups a difference in sensitivity between the CD4+ and CD8+ cells for the FN18 antibody could be noticed. From the data it appears that FN18 is immunosuppressive and does not have serious side effects. The data are in agreement with information available for the use of OKT3 in clinical immunosuppression. Thus, extrapolation of data from the rhesus monkey model to the clinical situation seems feasible. PMID- 3113977 TI - Activation of memory and virgin B cell clones in hyperimmune animals. AB - To study the long-term memory response, BALB/c mice were allowed to rest for over a year after a secondary immunization with the hapten 2-phenyl-oxazol-5-one (phOx). For the tertiary immunization two different protocols were used. In one protocol mice were injected i.v. and 3 days later spleen cells were fused to a nonproducing hybridoma line. PhOx-specific hybridomas were established and the sequence of the heavy and light chain mRNA was determined. This tertiary response resembled the diversity pattern of the secondary response with a further increase both in somatic mutations and in the average dissociation constant. The high number of somatic mutations demonstrates the persistence of memory B cell clones over a long time period. In the second protocol mice were boosted with an i.p. injection of alumprecipitated antigen phOx and 7 or 14 days later spleen cells were fused. Sequence analysis of heavy and light chain mRNA showed that these tertiary response antibody molecules had surprisingly few somatic mutations, indicating an activation of virgin B cell clones in these hyperimmunized animals. The maturation of these newly stimulated B cell clones seems to follow somewhat similar rules to those found for the primary response. It appears therefore that the two immunization protocols reflect the response of memory and virgin B cells, respectively. PMID- 3113978 TI - The role of L3T4+ cells in the pathogenesis of lupus in lpr-bearing mice. I. Defects in the production of interleukins 2 and 3. AB - Mice which bear the lpr gene spontaneously develop autoimmune syndromes characterized by massive expansion of an unusual T cell subset which is phenotypically Thy-1+, L3T4-, Lyt-2-, B220+. The mutant T cells are refractory to stimulation with mitogenic lectins and, by implication, are thought to be solely responsible for the defects in lymphokine production manifested by lpr mice. The contribution of the remaining L3T4+ T cell subset to the latter derangements has not been previously examined and is the focus of this study. We found that abnormalities in concanavalin A-induced interleukin 2 and 3 production in the spleens of MRL-lpr/lpr and C57BL/6.lpr mice occurred in the presence of limited infiltration with B220+, L3T4- T cells. Mixing experiments indicated that B220+ T cells were not suppressive. Furthermore, lpr spleen cells enriched for L3T4+ cells and depleted of sIg+, B220+ and Lyt-2+ cells demonstrated reductions in lymphokine production which were comparable to those seen in unfractionated preparations. Spleen cells from C57BL/6.lpr mice, enriched for L3T4+ cells, were also markedly impaired in a mixed leukocyte reaction in response to stimulator cells from the class II major histocompatibility complex mutant bm12. The results indicate that the aberrations in lymphokine production and proliferation in the spleen cells of lpr mice involve not only B220+ T cells but also L3T4+ cells and suggest a potential role for the L3T4+ subset in the pathogenesis of lupus in lpr bearing mice. PMID- 3113979 TI - Comparison of the clonal diversity of the B cell repertoires in adult mice that differ in the expression of cell surface IgD. AB - To determine whether the expression of surface IgD (sIgD) influences the extent of the expressed B cell repertoire, the clonal diversity of the B cell population in mice treated chronically with anti-IgD (delta) antibodies has been compared with the B cell repertoire observed in control animals, using the splenic focus limiting dilution B cell assay. The results show that the phosphorylcholine (PC) specific B cell precursor frequency in anti-delta antibody-treated mice is increased when compared with that of control mice. Isotype and idiotype (T15) analyses of PC clonal products from anti-delta antibody-treated and control mice revealed no distributional differences. Analyses of the 2,4-dinitrophenyl (DNP)- and fluoresein isothiocyanate-specific B cell repertoires confirmed that the equal or increased precursor frequencies observed in anti-delta antibody-treated mice are not specific for the PC antigen. The increased precursor frequency of B cells from anti-delta antibody-treated mice was not the result of increased homing of B cells from anti-delta antibody-treated mice to recipient spleens, since B cells from control mice homed twice as well to recipient spleens as did B cells from anti-delta antibody-treated mice. Other studies demonstrated that (a) on average, antibody-secreting clones were generated more slowly when B cells from anti-delta antibody-treated mice were used as a source of precursors than B cells of control mice and (b) both sIg- spleen cells and sIg+ spleen cells from anti-delta antibody-treated mice generated a higher frequency of specific antibody-secreting clones than did the corresponding populations from control mice. These observations suggest that a population of sIgM+sIgD- B cells exists that resembles sIgD+ B cells rather than neonatal or xid B cells in its ability to generate responses to PC and suggests that the sIgM+sIgD- B cells from anti delta antibody-treated mice are more responsive than are sIgM+IgD+ B cells, regardless of antigenic specificity, to the stimuli provided in the splenic focus system. Finally, this study suggests that the expression of sIgD does not influence the extent of the expressed B cell repertoire. PMID- 3113980 TI - Defective interleukin 2 receptor expression is associated with the T cell disfunction subsequent to bone marrow transplantation. AB - In the present work we have used monoclonal antibodies (mAb) as probes to attempt a dissection of the mechanisms underlying the immunodeficiency subsequent to bone marrow transplantation (BMT). To this end we have studied 19 allogeneic BMT recipients, analyzing the proliferative response of peripheral blood mononuclear cells (PBMC) after activation with either phytohemagglutinin (PHA), anti-CD3 or anti-CD2 mAb. All patients presented normal proportions of CD2+ and CD3+ lymphocytes, as assessed by flow cytometry. Our results indicated that in most cases both CD2 and CD3-mediated activation pathways were inefficient to trigger normal T cell proliferation. The addition of exogenous interleukin 2 (IL2) did not restore in most cases the proliferative response, pointing out that additional defects contribute to the hyporesponsiveness. This was more evident in the group of patients studied during the first 6 months. To further dissect the T cell defect we analyzed the effect of a phorbol ester (phorbol myristate acetate, PMA), which activates protein kinase C, on the anti-CD3-induced response. Our data showed that PMA synergized with anti-CD3 similarly to exogenous IL2, and restored the proliferative response only in certain cases. The expression of IL2 receptors (CD25) as assessed by cytofluorimetry, after either PHA or anti-CD3 and PMA stimulation, was shown to be depressed, and the addition of IL2 did not restore it. Finally, we observed that the early increase of intracytoplasmic Ca2+ after anti-CD3 stimulation was comparable to that detected in normal PBMC. Altogether these results indicate that a diminished CD25 expression is associated with the T cell defect, and cannot apparently be attributed to an inability of the CD3 molecule to transduce early activation signals thus suggesting that either protein kinase C itself or an as yet undefined metabolic step preceding IL2 receptor expression is abnormal in variable proportions of T cells after BMT, and constitutes another manifestation of this complex immunodeficiency. PMID- 3113981 TI - Eicosanoid formation by mammalian intestine. Effects of some intestinal secretagogues. AB - Intestinal tissues of man, rat, mouse, guinea-pig and rabbit were preincubated with laxatives, homogenised, and incubated with [14C]arachidonic acid. After extraction into chloroform, the eicosanoids were separated by thin layer chromatography. Metabolism of [14C]arachidonic acid into prostaglandins (PGs), and the lipoxygenase products LTB4 and 5-HETE, was stimulated by ricinoleic acid (100 micrograms/ml) or phenolphthalein (100 micrograms/ml), and to a lesser extent by picosulphate (125 micrograms/ml) and sulfosuccinate (200 micrograms/ml). Mannitol (500 micrograms/ml) had no effect. Indomethacin (1 microgram/ml) inhibited the stimulation of PG formation. The dual pathway inhibitor BW755C (1 microgram/ml) reduced the formation of prostaglandins, LTB4 and 5-HETE. In some experiments on rat colon, prostanoids were separated from lipoxygenase products, characterised by their chromatographic mobility and quantitated (relative amounts PGE2 greater than PGF2 alpha greater than TXB2 greater than PGD2). Their formation was enhanced by ricinoleic acid (100 micrograms/ml) and inhibited by either indomethacin or BW 755C (1 microgram/ml). The present results indicate that mammalian isolated gut tissue can convert [14C]arachidonic acid into both cyclo-oxygenase and lipoxygenase products, and support the suggestion that eicosanoids may participate in the laxative effect of some secretagogues. PMID- 3113982 TI - Dopamine D-2 auto- and postsynaptic receptors in the nigrostriatal system of the rat brain: localization by quantitative autoradiography with [3H]sulpiride. AB - In vitro receptor autoradiography with [3H]sulpiride (a selective D-2 antagonist) was used to assess the effect of 6-hydroxydopamine and ibotenic acid lesions of the caudate-putamen and substantia nigra pars compacta on D-2 dopamine receptors in rat brain. A marked reduction in [3H]sulpiride binding within the pars compacta of the substantia nigra resulted from lesions of the substantia nigra compacta with either toxin, while substantial reduction in binding within the caudate-putamen followed only ibotenate lesions of that structure. Since ( )sulpiride is a selective D-2 antagonist, these data confirm that autoreceptors on nigral DA neurons are of the D-2 type, while a portion of D-2 receptors in the caudate-putamen are postsynaptic on striatal neurons. PMID- 3113983 TI - Bepridil and valproate retard Na+ reactivation in Myxicola. AB - Two drugs were examined, each causing a similar specific modification of Na+ channel inactivation gating when internally applied to voltage-clamped Myxicola giant axons. Bepridil is an antianginal-antiarrhythmic agent with vasodilator and direct cardiac inotropic effects. Sodium valproate has anticonvulsant activity and causes use-dependent inhibition of repetitive firing in CNS neurons. Bepridil and sodium valproate caused a dose-dependent decrease in maximum Na+ conductance (KD = 25 microM for bepridil; KD = 0.5 mM for valproate). More importantly, at half-maximal blocking concentrations both drugs shifted steady state Na+ inactivation in the hyperpolarizing direction (by 30 mV for bepridil; 15 mV for valproate) and slowed the recovery of Na+ channels from inactivation (by 300% for bepridil; 60% for valproate). There was no effect on the K+ conductance, voltage dependence of Na+ activation, or the time-dependence of inactivation of conducting channels. Neither produced non-inactivating Na+ current during long depolarizing steps. PMID- 3113984 TI - Sympathetic nerve-mediated release of ATP from the guinea-pig vas deferens is unaffected by reserpine. AB - The release of ATP from the guinea-pig vas deferens was measured using the luciferin-luciferase assay. The effects of reserpine, tetrodotoxin, 6 hydroxydopamine and guanethidine on this efflux were investigated. Reserpine, which produced extensive loss of noradrenaline (NA) (about 99%) and eliminated the second phase of the nerve-mediated contraction, failed to impair either ATP release from the vas deferens or the concomitant 'twitch' contraction; in fact both were increased. Therefore the neurotransmitter mediating the twitch cannot be NA, thus excluding the gamma-receptor hypothesis. Furthermore, since the release of ATP is unaffected by reserpine, it is unlikely that ATP is being released from smooth muscle as a consequence of the post-junctional actions of NA. Tetrodotoxin, 6-hydroxydopamine and guanethidine substantially reduced or abolished the release of ATP and both phases of the nerve-mediated response. To conclude, in the guinea-pig vas deferens, ATP co-released with NA from sympathetic nerves, mediates the twitch phase of the contraction and its underlying electrical events. PMID- 3113985 TI - Neurochemical and behavioural evidence for an agonist action of 1-[2-(4 aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY 165163) at central 5 HT receptors. AB - 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY 165163, PAPP) (1 mg/kg s.c.) significantly decreased 5-hydroxytryptophan (5-HTP) accumulation in cortex, hippocampus, striatum, septum, pons + medulla and midbrain and increased DOPA accumulation in the cortex and striatum following inhibition of aromatic amino acid decarboxylase with NSD 1015. LY 165163 increased food intake in non-food-deprived rats over 2, 4 and 24 h after administration. Depletion of brain 5-hydroxytryptamine (5-HT) by parachlorophenylalanine (pCPA) prevented the hyperphagic effect over 2 and 4 h after treatment with LY 165163 (1 mg/kg). Components of the postsynaptically mediated 5-HT behavioural syndrome were not detected at doses of LY 165163 between 1 and 10 mg/kg, although locomotion was increased at lower doses and the rats were inactive at the highest dose. Results in general indicate that LY 165163 is a centrally active agonist at 5-HT presynaptic receptors. PMID- 3113986 TI - Verapamil enhances the non-adrenergic twitch response of rat vas deferens. AB - Verapamil (3 X 10(-6)-3 X 10(-5) M) enhanced the twitch contractions of the epididymal and prostatic portions of vas deferens stimulated at 0.1 Hz. This verapamil effect was essentially similar to those of diltiazem, D-600 and Bay K 8644. However, when stimulation at 2 Hz was used verapamil (3 X 10(-5) M) attenuated the contractions of the epididymal portion by half but still augmented those of the prostatic portion. Verapamil enhanced the reserpine- and prazosin resistant component of the stimulation-induced contractions of both portions of the vas deferens. Yohimbine augmented the twitch response but attenuated the verapamil-augmented response. Verapamil did not augment norepinephrine- or tyramine-induced contractions whereas it augmented ATP-induced contractions of the prostatic portion but not of the epididymal portion. Verapamil increased the stimulation-evoked 3H-efflux from the vas deferens labelled with [3H]norepinephrine. It is suggested that verapamil augments non-adrenergic responses of both portions of the vas deferens by acting as a Ca agonist on the prejunctional site to increase the release of co-transmitter, or by acting on the postjunctional site to enhance the action of the substance released. Its effect in augmenting norepinephrine release is concluded not to contribute to the potentiating action. PMID- 3113987 TI - 6-Hydroxydopamine lesions reduce specific [3H]sulpiride binding in the rat substantia nigra: direct evidence for the existence of nigral D-2 autoreceptors. AB - [3H]Sulpiride bound to substantia nigra homogenates in a saturable manner and with a pharmacological profile typical of a specific D-2 ligand. Unilateral 6-OH dopamine (DA) lesions of the nigrostriatal DA neurons reduced by 27-46% the Bmax of the specific [3H]sulpiride binding in substantia nigra homogenates depending on the time after 6-OHDA lesion and significantly increased the Bmax in the caudate. KDs remained unchanged in both areas. The localization of specific [3H]sulpiride binding and its reduction in the substantia nigra of the 6-OHDA lesioned side were confirmed by quantitative autoradiography. The results provide evidence for the existence of D-2 autoreceptors in substantia nigra. PMID- 3113988 TI - Preliminary characterization of cell surface-extracellular matrix linkage complexes in cultured retinal pigmented epithelial cells. AB - In this report, we describe the relative distribution of vinculin, talin, and fibronectin in cultured retinal pigmented epithelial cells from chick embryo eyes. We show that in these cells vinculin is present in both focal cell substratum and cell-cell contacts, whereas talin is present only in the cell substratum contacts. When cells are double-labeled for talin and fibronectin and viewed at the substratum level, fibronectin is not detectable and talin is concentrated in plaques corresponding to focal contacts. However, when the same cells are viewed at the apical level, both talin and fibronectin are present in a fibrillar pattern. In addition to fibrils which are both talin- and fibronectin positive, there are areas which are either talin-positive and fibronectin negative or, vice versa, talin-negative and fibronectin-positive. These observations indicate an interesting variability in the composition of transmembrane linkages in retinal pigmented epithelial cells in vitro. PMID- 3113989 TI - Identification of a zona-binding protein from boar spermatozoa as proacrosin. AB - The initial stages of fertilization in vertebrates and invertebrates are thought to involve complementary recognition molecules on spermatozoa and eggs. In a previous work (C. R. Brown and R. Jones, 1987, Development) we described one such putative molecule (a protein of approximate molecular weight 53 kDa) in detergent extracts of boar spermatozoa that has affinity for glycoproteins from the zona pellucida of pig eggs. This molecule has now been identified as proacrosin, the zymogen form of the acrosomal protease acrosin, on the basis of its electrophoretic behavior, the ability of zona glycoproteins to recognize and bind to proacrosin on Western blots, and the cross-reactivity of specific antisera to the 53-kDa molecule and proacrosin. A role is proposed for this enzyme in binding the sperm head to the zona pellucida during the initial stages of sperm-egg interaction. PMID- 3113990 TI - Mitochondrial DNA and life span changes in normal and dewinged Drosophila at different temperatures. AB - At 11 and 30 degrees C there was no change in the amount or in the buoyant density of nuclear DNA of male Oregon R Drosophila melanogaster with aging. When normal flies were maintained at 11 degrees C (at which temperature they do not fly), mitochondrial DNA content declined gradually with aging and 39.4% of the original mitochondrial DNA was lost at the median survival time of 152 days of age. For normal flies maintained at 30 degrees C, 86.5% of the mitochondrial DNA was lost during aging at the median survival time of 25 days. In contrast only a 39.2% decrease in the mitochondrial DNA occurred in dewinged flies maintained at 30 degrees C. A slow phase of mitochondrial DNA loss appears to be related to aging and a fast phase to flight activity. Removing the wings of flies eliminates the fast phase of DNA loss but only slightly improves life span (by less than 10%). Lowering the environmental temperatures to 11 degrees C also eliminates fast phase DNA loss and decreases the rate of the slow phase DNA loss. We conclude that mitochondrial DNA loss is related to both physical activity and to the aging process itself. PMID- 3113991 TI - Successful selection for increased longevity in Drosophila: analysis of the survival data and presentation of a hypothesis on the genetic regulation of longevity. AB - Long lived strains of Drosophila melanogaster have been generated via 25 generations of artificial selection. The mean and the maximum lifespans have been increased both absolutely as well as relative to the controls. The mean lifespan of the selected line now exceeds the maximum lifespan of the controls. The data shows that this increase is entirely accounted for by a genetically based delay in the onset of senescence. Identification and analysis of biomarker data involving reproductive functions supports this interpretation and leads to a suggestion of the processes involved in the lifespan extension. This increase in the duration of the pre-senescent period is under both genetic and environmental control. Senescence itself is not under genetic control and appears to occur stochastically. Selection for decreased longevity was unsuccessful, supporting the concept of a minimum species specific lifespan. A testable hypothesis regarding the biphasic mode of gene regulation of senescence is presented in which a gene-environment interaction takes place in larval life that results in a temporal reprogramming of other, presumably structural, genes which act in adult life at a time prior to the onset of senescence. PMID- 3113992 TI - Successful selection for increased longevity in Drosophila: analysis of the survival data and presentation of a hypothesis on the genetic regulation of longevity. PMID- 3113993 TI - Regulation of the activity of heme degradative enzymes in K562 erythroleukemic cells: induction by thymidine. AB - Heme oxygenase is rate-limiting in the heme degradative pathway, and its activity is induced by a host of chemicals. In K562 human erythroleukemic cells, heme oxygenase activity was not increased by exposure to potent inducers, such as cobalt chloride, bromobenzene, and heme. Indeed heme treatment severely suppressed the enzyme activity, and at 18 h the activity measured less than 5% of the control. Heme and cobalt chloride did not inhibit activities of NADPH cytochrome c (P-450) reductase and biliverdin reductase to a marked degree. In contrast, treatment of cells with thymidine/hypoxanthine alone, or in combination with cobalt chloride, caused an increase in the activity of three enzymes of heme degradation. It is suggested that with thymidine, which is a committing inducer of hemoglobin synthesis, the induction of activity of the three enzymes of the heme degradation pathway is coupled with cell differentiation. On the other hand, in the case of heme, a noncommitting inducer of hemoglobin synthesis, induction of hemoglobin synthesis and increase in heme degradation activity may be independent. PMID- 3113994 TI - Autoantibodies in infections of the respiratory tract with Mycoplasma pneumoniae or influenza virus A. AB - The sera from 26 patients with serological evidence of infection with Mycoplasma pneumoniae and 23 patients with influenza virus A infection were examined for autoantibodies to smooth muscle, cell nuclei and 'reticulin'. There is an increased incidence of autoantibodies to smooth muscle (46%) in the serum of patients infected with M. pneumoniae. There is no increase in autoantibodies to cell nuclei or 'reticulin' in these patients. There is no increased incidence of autoantibodies in patients infected with influenza virus A. The possible aetiology of the raised incidence of smooth muscle autoantibodies in the patients with M. pneumoniae is discussed. PMID- 3113995 TI - No effect of rifampicin upon urinary light chain excretion. PMID- 3113996 TI - Effect of hyperthermia upon gamma-ray induced crossing-over in an excision repair deficient male Drosophila melanogaster. AB - Hyperthermia of 1 h at 38 degrees C did increase gamma-ray induced crossing-over in meiotic cells of male larvae and adults. However, there was considerably less effect of the heat treatment upon radiation induced crossing-over (a chromosome breakage event) in an excision repair mutant y mei-9a. PMID- 3113997 TI - Identification of a UDP-Gal:beta-galactoside beta 1----3-galactosyltransferase in the albumen gland of the snail Lymnaea stagnalis. AB - Detergent extracts of the albumen gland of the snail Lymnaea stagnalis contain an enzyme activity that transfers Gal from UDP-Gal to acceptor substrates with terminal non-reducing beta-galactose residues. The products formed with lactose (Gal beta 1----4Glc) as the acceptor were characterized by HPLC, and subjected to 400-MHz 1H-NMR and methylation analysis. The main product was shown to have the structure Gal beta 1----3Gal beta 1----4Glc. Therefore, the galactosyltransferase can be identified as a UDP-Gal:beta-galactoside beta 1----3 galactosyltransferase. In view of its linkage and acceptor specificity, the enzyme may be essential to the biosynthesis of galactogen, the main polysaccharide produced by albumen glands of L. stagnalis. PMID- 3113998 TI - Possible involvement of eicosanoids in the actions of sympathetic hepatic nerves on carbohydrate metabolism and hemodynamics in perfused rat liver. AB - In isolated rat liver perfused at constant pressure with Krebs-Henseleit buffer containing 5 mM glucose, 2 mM lactate, 0.2 mM pyruvate and 0.1% bovine serum albumin, perivascular nerve stimulation (20 V, 20 Hz, 2 ms) and infusion of ATP (100 microM), noradrenaline (1 microM) or arachidonic acid (100 microM) caused an increase in glucose and lactate output and a reduction of perfusion flow. The metabolic effects of nerve stimulation but not those of ATP and noradrenaline were inhibited strongly by the phospholipase A2 inhibitor bromophenacyl bromide (BPB, 20 microM) and the cyclooxygenase inhibitor indomethacin (Indo, 20 microM) and only slightly by the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 20 microM). In contrast, the hemodynamic effects not only of nerve stimulation but also of ATP and noradrenaline were inhibited strongly by BPB and Indo and slightly by NDGA. The metabolic and hemodynamic actions of arachidonate were inhibited specifically by Indo. These results suggest that the effects of nerve stimulation were at least partially mediated or modulated by eicosanoids, especially by prostanoids. PMID- 3113999 TI - Detection of multiple forms of Gi alpha in HL60 cells. AB - Comparison of cDNA sequences from multiple sources predicts a genus of highly homologous but structurally distinct G protein alpha-subunits, designated as Gi alpha, that may include the alpha-subunit of the functionally defined adenylate cyclase inhibitory G protein. Using specific oligonucleotide probes on Northern blots, we show that Gi alpha-2 and Gi alpha-3, but not Gi alpha-1, are expressed in HL60 cells. Antisera raised against synthetic peptides from regions predicted to be conserved (AS6) and divergent (LE3) among Gi alpha subtypes bind to a 40 kDa protein in Western blots of HL60 membranes. AS6 identifies an additional protein at 41 kDa. Thus, Northern blot and immunoblot results show that at least two Gi alpha subtypes, a 40 kDa protein likely to correspond to Gi alpha-2 and a 41 kDa protein possibly representing Gi alpha-3, may be expressed in a single cell type. PMID- 3114000 TI - Unusual 5 S ribosomal RNAs. An analysis of individual segments can reveal phylogenetic relatedness. AB - Sequence comparisons of 5 S and other ribosomal RNAs by segments can be useful in understanding anomalous primary and secondary structures and in assessing phylogenetic relationships. In a segmented analysis, the 5'-half of the Chlamydomonas reinhardii chloroplast 5 S ribosomal RNA is found to have a very close sequence homology to the green plant chloroplast and cyanobacterial 5 S RNAs; however, the 3'-half has a highly unusual sequence. Further comparisons of homologies between regions of the 5 S RNAs from C. reinhardii and the green plant chloroplasts suggest that genetic rearrangements within the 5 S DNA may have produced the unusual sequence at the 3'-half. Segmented analyses of the C. reinhardii and green plant chloroplast 5 S RNAs suggest a close relationship which is not revealed by overall sequence comparisons. PMID- 3114001 TI - Subcellular localization of a PhoE-LacZ fusion protein in E. coli by protease accessibility experiments reveals an inner-membrane-spanning form of the protein. AB - Protease accessibility experiments were employed to localize a PhoE-LacZ hybrid protein, encompassing a large N-terminal fragment of the outer membrane PhoE protein of E. coli, fused to beta-galactosidase, at the subcellular level. In previous studies, this protein was shown to co-fractionate with the outer membrane, whereas immunocytochemical methods suggested a cytoplasmic location. The present results confirm the latter localization. Moreover, it appears that a minor amount of hybrid protein spans the inner membrane, with the PhoE moiety in the periplasm and the beta-galactosidase moiety in the cytoplasm. These membrane spanning proteins might be responsible for the lethal jamming of the export machinery, observed upon induction of synthesis of the protein. PMID- 3114002 TI - Arachidonic acid-induced release of calcium in permeabilized human neutrophils. AB - The addition of arachidonic acid to a suspension of digitonin-permeabilized human neutrophils was found to induce, in a dose-dependent manner (ED50 about 15 microM), the release of calcium from internal stores. Arachidic acid was without effect, while linoleic acid and linolenic acid were (on a concentration basis) at least 5-times less active than arachidonic acid. The activity of arachidonic acid appears to be due to the fatty acid itself and not to one of its metabolites. The pool of calcium mobilized by arachidonic acid includes that sensitive to inositol 1,4,5-triphosphate. These results demonstrate a significant intracellular role for arachidonic acid at the level of the internal mobilization of calcium in human neutrophils. PMID- 3114003 TI - Effects of Ca2+, theophylline and promethazine on protein phosphorylation in intact cells of rabbit ileum. Correlation with active Na and Cl absorption. AB - The effects of Ca2+, theophylline and promethazine on the phosphorylation of microvillus membrane proteins have been studied in rabbit ileal epithelial cells, using intact cell phosphorylation techniques followed by purification of microvillus membranes, separation of peptides by two-dimensional polyacrylamide gel electrophoresis, and quantitation of phosphorylation by computerized densitometry of autoradiograms. The Ca2+ ionophore A23187 caused increased phosphorylation of four and possibly five polypeptides; theophylline increased phosphorylation of three peptides, two of which had the same Mr and pI values as the peptides altered by the Ca2+ ionophore; promethazine decreased the phosphorylation of one of the peptides increased by Ca2+ ionophore. The phosphorylated peptides, which respond similarly to more than one agent which affect ileal Na and Cl absorption, could be involved in the regulation of NaCl absorption either as transport proteins or regulators of transport proteins. PMID- 3114004 TI - The phorbol ester, TPA, increases transepithelial epidermal growth factor flux. AB - Exposure of cultured kidney epithelial (LLC-PK1) cell sheets to 10(-7) M TPA, a potent tumor promoter and activator of protein kinase C, initiates within minutes a drop in the transepithelial voltage across these sheets. This fall in potential difference correlates with an over 40-fold increase in the transepithelial flux of 1 mM D-mannitol, suggesting that the intercellular junctions have become leaky. Dual labeling experiments with 1 mM D-[14C]mannitol and 10 nM 125I-EGF show that after promoter treatment, a 7-fold increase in net 125I flux accompanies the increase in mannitol flux. Gel filtration and gel electrophoresis indicate that for control cell sheets only 15% of the transited 125I is actually EGF, whereas with TPA-treated cell sheets, 60% of the 125I which passed across is EGF. These percentages permitted determination of actual EGF flux values, and show that TPA treatment engenders a 35-fold increase in transepithelial EGF flux. Diacylglycerols also increase the junctional permeability of these cells, thereby suggesting the involvement of protein kinase C. PMID- 3114006 TI - Fast neutrons in the treatment of locally advanced breast cancer. AB - The clinical investigation of fast neutrons at Hammersmith Hospital included 17 patients who between them had 20 T4 breast cancers. The majority of these tumours were ulcerated and all were painful. Ten had recurred after multiple other therapies. Complete local regression was achieved in all but one (95%) and no tumour recurred. Symptoms were relieved in all cases. Median survival was 26 months. Three patients developed small areas of skin necrosis following trauma of previous radiation. All the neutron treated breasts became fibrosed, but this was painless. Neutron treatment needed only 12 attendances over 28 days, in contrast to the best results from photon therapy which required 6-7 weeks followed by implant of radioactive wire and/or surgical excision. One patient who had bilateral tumours received neutrons to the left breast and X-ray therapy (photons) to the right. The photon treated tumour did not completely regress and recurred. The neutron treated one completely regressed and did not recur. Neutrons were also more effective than tamoxifen which causes complete regression in only about 30% of cases. It is suggested that neutron therapy is indicated for locally advanced tumours which do not respond to hormones. Since metastases were a common cause of death, there remains a need for an effective adjuvant treatment, acceptable to elderly patients. PMID- 3114005 TI - Location and sequence characterization of the major phosphorylation sites of the high molecular mass neurofilament proteins M and H. AB - Diagonal fingerprinting allows the specific purification of those tryptic peptides which change electrophoretic mobility due to a dephosphorylation step introduced after the first dimension. Nine tryptic peptides from the tail domain of porcine neurofilament M protein identify a minimum of 6 phosphorylated serines. Unexpectedly, four of the nine peptides characterize a region of degenerate repetitive sequences. Results on neurofilament H tail, although less complete, yield longer sequences of degenerate repetitive character. Here, all serines present appear to be contained in a lysine-serine-proline unit. This motif also occurs in some but not all M peptides. We suggest that degenerate repetitive sequences in neurofilament M and H tails have a high species-specific drift. PMID- 3114007 TI - Primary IgG-lambda immunocytoma of the urinary bladder. AB - Primary malignant lymphoma of the urinary bladder is extremely rare. This report documents on a case of primary IgG lambda immunocytoma of the urinary bladder. PMID- 3114009 TI - Ovarian follicular development in oral contraceptive cycles. AB - The cyclic changes in serum hormone concentrations, ovarian follicular development, uterine size, and endometrial appearance have been observed in 58 spontaneous ovulatory cycles and compared with 22 initial cycles of oral contraceptive (OC) therapy. A far greater inhibitory effect on the ovary was achieved by starting contraception on day 1 of the cycle rather than on day 5. The relevance of these findings with regard to OC failures is discussed. PMID- 3114010 TI - Superovulation with intrauterine insemination in the treatment of infertility: a possible alternative to gamete intrafallopian transfer and in vitro fertilization. AB - In vitro fertilization and embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT) are used to treat intractable infertility in women with no distortion of the pelvic viscera, despite the lack of controlled trials demonstrating efficacy. The mechanism of any purportedly enhanced cycle fecundity in ovulatory women without significant distortion of the pelvic viscera is unclear, but both GIFT and IVF-ET increase the number of male and female gametes at the site of fertilization. Intrauterine insemination (IUI) during human menopausal gonadotropin (hMG)-stimulated superovulatory cycles has similar potential but does not require oocyte retrieval. To evaluate the possibility that simply increasing the number of gametes at the site of fertilization might account for pregnancies attributed to IVF-ET and GIFT, the authors retrospectively analyzed the outcome of couples undergoing IUI during hMG cycles between 1983 and 1986 in women with normal pelvic anatomy. IUI during hMG stimulated cycles yielded a cycle fecundity (f) of 0.17 for endometriosis, 0.29 for cervical factor, and 0.19 for idiopathic infertility, which approaches the fecundity of normal women and equals or exceeds that reported for IVF-ET and GIFT. The authors conclude that treatment with IUI in hMG cycles, alleviating the need for invasive oocyte retrieval, should be considered for inclusion in a randomized, controlled trial in comparison with IVF-ET and GIFT. PMID- 3114011 TI - Comparison of urinary human follicle-stimulating hormone and human menopausal gonadotropins for ovarian stimulation in an in vitro fertilization program. AB - This report compares the effects of human menopausal gonadotropin (hMG) and purified urinary human follicle-stimulating hormone (hFSH) protocols in patients with irreparable tubal disease as the sole indication for in vitro fertilization embryo transfer (IVF-ET). The hFSH protocol was associated with significantly more uniform folliculogenesis and more effective steroidogenesis than the one using hMG. In addition, the hFSH protocol showed a trend toward more oocytes per laparoscopy and more embryos per transfer than the hMG group, although the difference was not statistically significant. More oocytes in the hMG group were classified as immature when compared with the hFSH group (P less than 0.05). Pregnancy rates in both groups were not significantly different. An allergic drug reaction that occurred in one patient on the hFSH protocol is the first such reaction reported with hFSH in the literature. The hFSH protocol is associated with a trend toward parameters that correlate with improved success rates in the IVF-ET program. PMID- 3114008 TI - The association between smoking and female infertility as influenced by cause of the infertility. AB - Smoking histories were compared in 901 women with infertility of different types and 1264 women admitted for delivery at seven collaborating hospitals. The relative risk for infertility associated with cigarette smoking prior to the infertility diagnosis for nulliparous cases or first live birth for controls was calculated using a multivariate logistic-regression model to control for potential confounding factors, including center, age, religion, education, number of sexual partners, and contraceptive use. The adjusted risk for infertility attributed primarily to cervical factor (n = 96) was 1.7 (P = 0.04), to tubal disease unrelated to endometriosis (n = 225) was 1.6 (P = 0.009), to ovulatory factor (n = 389) was 1.0 (not significant [NS]), and to endometriosis (n = 191) was 0.9 (NS). The authors conclude that cigarette smoking is significantly associated only with certain types of primary female infertility. PMID- 3114012 TI - Estrone-3-glucuronide chemiluminescence immunoassay: an alternative method for monitoring induction of ovulation with human menopausal gonadotropin in an in vitro fertilization program. AB - A simple, rapid, and sensitive solid-phase immunoassay procedure for the determination of estrone-3-glucuronide (E1-3-G), which uses chemiluminescence as the end point in unextracted morning urine, is described. Thirty-one patients undergoing induction of ovulation in an in vitro fertilization (IVF) unit participated in the study. From day 3 of the menstrual cycle until the day of hCG administration, morning blood samples and morning urine specimens were collected for the determination of serum 17 beta-estradiol (E2) and urine E1-3-G, respectively. A good correlation was noted between E2 measured by radioimmunoassay (RIA) and the E1-3-G measured by chemiluminescence immunoassay (CIA), from day 5 up to the day of hCG administration (0.6 less than r less than 0.85, P less than 0.001). It is evident from this study that the CIA measurement of E1-3-G in morning urine is an accurate and rapid (2.5 hours) method and is convenient for monitoring induction of ovulation with human menopausal gonadotropins. PMID- 3114013 TI - Incidence of multiple gestations in the presence of two or more mature follicles in the conception cycle. PMID- 3114014 TI - Subcloning of prochymosin cDNA for Plac controlled expression. AB - Two overlapping segments of prochymosin cDNA clones (Liebscher et al., 1985) were used to construct plasmids that expressed an activable zymogen product and thus verified the integrity of the reverse transcripts. The pUC9 vector was used for the expression, under the control of the lac promoter. The expression product (a fused protein consisting of the N-terminus of beta-galactosidase, a polylinker coded peptide and prochymosin from its 5th amino acid) displayed, upon activation by the usual procedure, the properties of calf chymosin. The active product was identified by milk-clotting tests, "caseinography" and protein electrophoresis of immunoprecipitates. The "boxing" of prochymosin cDNA in the constructed plasmids makes them a versatile source of this cDNA for other expression constructs. PMID- 3114015 TI - In vitro sensitivity of rat ovarian follicles to the direct action of various hormones applied in particular stages of sexual cycle. AB - The direct action of various hormones on the ovary of adult rat ovaries has been investigated. The ovaries were surgically exposed at particular stages of sexual cycle i.e. in estrus, metestrus, diestrus and proestrus, and were injected with various doses of gonadotropic hormones. Injected ovaries were excised 56 hrs after injection and examined histologically. The reactivity of the ovaries to hormone applied was dependent on stage of the cycle. The considerable increase of the amount of t1 and t2 follicles was observed after injection of gonadotropins in estrus stage. In metestrus stage the influence of gonadotropins on the follicles more advanced in development was pronounced. Numerous follicles t3 appeared in diestrus under the influence of all used hormones. PMID- 3114016 TI - Pericardial heterografts: a method for leaflet mechanical property control. PMID- 3114017 TI - Distributions and properties of cytochromes P-450 and cytochrome P-450 reductase from rat colon mucosal cells. AB - Cytochrome P-450 reductase and cytochrome P-450 fractions have been separated and partially purified from colonic mucosal microsomes of rat pretreated with phenobarbital or beta-naphthoflavone. Colonic cytochrome P-450 reductase has a molecular weight of 76,000. The Km values of colonic cytochrome P-450 reductase for the artificial electron acceptors cytochrome c, ferricyanide, and dichlorophenolindophenol and the electron donor NADPH are 6, 50, 11 and 11 microM, respectively. Immunochemical techniques identified the presence of beta naphthoflavone Forms 1, 4 and 5 after beta-naphthoflavone treatment but beta naphthoflavone Forms 1 and 4 and phenobarbital Form 1 after phenobarbital treatment. PMID- 3114018 TI - Immunochemical analysis of porcine cardiac C-protein. AB - C-protein has been isolated from pig heart and its immunochemical properties studied. It is extracted with myosin, and separated from the myosin on a DEAE Sephadex column. The amount of C-protein recovered from crude myosin is approx. 3.5%. The molecular weight of C-protein is 150,000. Anti-C-protein serum reacts with crude myosin and purified C-protein but not with purified myosin in immunodiffusion plates. Cardiac C-protein does not react with anti-skeletal white muscle C-protein serum. Immunoblotting experiments show that anti-cardiac C protein serum reacts with a Mr = 150,000 component in myofibrils or crude myosin. C-protein is located in the A-band, except the M-line region, of the myofibrils. These results indicate that C-protein is an intrinsic component of the thick filaments in pig heart myofibrils. PMID- 3114019 TI - The reactive sites of proteinase inhibitors from Erythrina seeds. AB - Although the Kunitz-type proteinase inhibitors from the seeds of various Erythrina species have similar molecular weights (approximately 20,000), and share many other chemical characteristics, they could nevertheless be divided into three groups on the basis of their relative abilities to inhibit chymotrypsin, trypsin and tissue plasminogen activator. Group a inhibitors were relatively specific for chymotrypsin; they were poor inhibitors of trypsin and had no apparent effect upon tissue plasminogen activator. Group b proteins inhibited trypsin strongly and chymotrypsin slightly less effectively. They had no effect upon t-PA. Group c inhibitors inhibited trypsin, chymotrypsin and t-PA. Analysis of the amino acid composition of the three groups of inhibitors revealed major differences in alanine content. Minor differences in the content of most other amino acids were also noticed. Group b and group c inhibitors had, in most cases, the same reactive sites (Arg-Ser). The sequences neighbouring the reactive sites showed a significant degree of homology. Chemical modification of arginine in proteinase inhibitors from the seeds of E. latissima and soybeans using 1-2 cyclohexanedione confirmed the presence or absence of arginine in the reactive sites. PMID- 3114020 TI - Study of circadian correlations between acetylcholine muscarinic receptor and brain glycosyltransferases by multivariate analysis. AB - Circadian variations of the acetylcholine muscarinic receptor and some glycosyltransferases were studied in brain using multivariate analysis. Highly significant correlations exist between fucosyltransferase, sialyltransferase and galactosyltransferase and to a lesser extent between both of these enzymes and acetylcholine receptor. No correlation appeared between these enzymes and dolichol phosphate mannose synthase. PMID- 3114021 TI - Heterogeneity of acid beta-galactosidase from rabbit kidney. AB - 1. Rabbit kidney acid beta-galactosidase can be resolved into three peaks (named A3, A2 and A1) by gel-filtration chromatography. Their estimated molecular weights were: more than 250,000, 150,000 and 17,000 respectively. 2. The purified acid form appeared as a single band of protein (Mr = 28,000) on electrophoresis in the presence of sodium dodecyl sulphate, suggesting that forms A3 and A2 are multimeric forms of beta-galactosidase A1. 3. Treatment with neuraminidase from Clostridium perfringens converts form A3 into a more basic form. This phenomenon occurs also when this form is stored for a week at 4 degrees C and parallels its disaggregation. 4. The data suggest that the sialic acids present in the multimeric forms are involved in the aggregation of the acidic form of beta galactosidase. PMID- 3114022 TI - The specific activities of mesophilic and thermophilic proteinases. AB - 1. Most enzymes from extreme thermophiles do not possess higher specific activities than similar enzymes from mesophiles (measured at their respective growth temperatures). 2. However, using protein substrates, the specific activities of thermophilic proteinases are considerably higher than those of most microbial and eukaryotic proteinases. 3. This property could be attributed to purely kinetic influences on the enzyme, to some specific "design" feature of the proteinase, or to the effects of temperature on the substrate. 4. Comparisons of the rates of hydrolysis of large and small substrates by both mesophilic and thermophilic proteinases suggest that temperature-induced changes in substrate susceptibility are a major factor. PMID- 3114023 TI - Arachidonic acid and leukotriene synthesis in relation to lung disease. PMID- 3114024 TI - A comparative study of drug-metabolizing enzymes present in isolated rat liver parenchymal, Kupffer and endothelial cells. PMID- 3114025 TI - Antisera against estrogen synthetase from human placental microsomes. Antibody characterization and cross-reactivity studies in other organs. AB - Antibodies were obtained against both protein components of the cytochrome P-450 enzyme system responsible for estrogen biosynthesis, estrogen synthetase (aromatase), from human placental microsomes. The antiserum against the NADPH cytochrome P-450 reductase component (antiserum denoted RE-DFBIV) gave a single major band at the Mr of the authentic enzyme by immunoblotting after electrophoretic separation of SDS-solubilized microsomes and inhibited both the reductase and aromatase activities in human placental and endometrial microsomes (Tseng, L. and Bellino, F.L. (1985) J. Steroid Biochem. 22, 555-557) and in homogenates of cultured aromatase-stimulated human endometrial stromal cells and human ovarian microsomes. The antiserum against the cytochrome P-450 component of aromatase (antiserum denoted P45FBIII) also gave a single band at the Mr of the authentic protein by immunoblotting after electrophoresis, and inhibited aromatase activity in homogenates of human placental microsomes, ovarian and decidual particulate fractions and cultured aromatase-stimulated endometrial stromal cells. This antiserum had no effect on NADPH-cytochrome c reductase activity in any of the systems studied. We conclude that these antiserum preparations separately recognize the NADPH-cytochrome P-450 reductase and cytochrome P-450 components of aromatase in human placenta, ovary, decidua and endometrium. Epitopes on these aromatase component proteins involved in enzyme activity are shared among these various human tissue sources. PMID- 3114027 TI - The proteoglycan chondroitin sulfate is present in a subpopulation of cultured astrocytes and in their precursors. AB - We have used an antibody raised against the bovine nasal cartilage proteoglycan chondroitin sulfate (CS) digested with chondroitinase ABC (anti-CS serum) to stain cerebellar glial cells maintained in culture. In cultures grown in the presence of serum, the antibody stained a subclass of GFAP+ astrocytes which we have previously shown to selectively bind the monoclonal antibodies A2B5 and LB1. Also the direct bipotential precursors of these cells, capable of differentiating into GFAP+ astrocytes or into Gal-C+, O1+ oligodendrocytes depending on the culture conditions, were stained, but stopped to produce CS when they differentiated into oligodendrocytes. PMID- 3114026 TI - Independent control of citrate production and ornithine decarboxylase by prolactin in the lateral lobe of the rat prostate. AB - Prolactin stimulated the citric acid content of the lateral lobe of the prostate of androgenized-hypophysectomized rats in a time-dependent manner. This stimulation of citric acid levels was not blocked by pretreatment of the animals with the ornithine decarboxylase (ODC) inhibitor, alpha-difluoromethyl ornithine (DFMO), suggesting that the prolactin induction of citric acid in this organ is not mediated through activation of the ODC. The efficacy of the dose of inhibitor used was monitored by analysis of the diamine product of ODC, putrescine. Further evidence of an independent control of citric acid and polyamine synthesis in the lateral lobe was provided by their differing age distributions in intact animals. ODC activity decreased sharply with age, whereas the tissue concentrations of citric acid remained relatively constant. Both studies suggest that although citric acid and ODC are modulated by prolactin, their synthesis or activation are controlled independently of each other. PMID- 3114028 TI - Effect of bombesin on glucose-induced insulin release in humans. AB - The effect of bombesin on basal and glucose-stimulated insulin release was studied in male healthy volunteers. Glucose was administered by oral, intravenous or intraduodenal route during saline or bombesin infusion (5 ng/kg/min for 60 min). The peptide had no significant effect on basal levels of glucose and insulin. However, during its administration, the insulin response and the expected rise in blood glucose after oral glucose load (50 g) were strongly inhibited, and the gastric emptying of liquids was significantly delayed. On the contrary, the insulin response to intravenous glucose (20 g) was significantly increased by bombesin without changes in plasma glucose levels. Finally, when glucose was infused into the duodenum, thus bypassing the stomach, the insulin response was significantly increased by the peptide. In this case, too, plasma glucose levels after glucose load were virtually identical during either bombesin or saline infusion. These data clearly demonstrate that the direct effect of bombesin on insulin release is stimulatory and suggest that the inhibitory effect observed after oral glucose is connected with the action of the peptide on gastric emptying, the delay of which slows the entry of glucose into the small bowel. PMID- 3114029 TI - Plasminogen activators during differentiation of the human kidney. AB - Tissue-type plasminogen-activator antigenicity was immunohistochemically localized in the developing glomerulus of human embryonic kidneys using antibodies raised against a highly purified HeLa-cell activator [43]. At the very beginning of the S-shaped-body stage of glomerular differentiation, tissue-type activator antigenicity seemed to be co-distributed with a marker of invading endothelial cells, i.e., Ulex europaeus lectin. However, during further stages of glomerular remodelling and maturation, this plasminogen activator was also localized around developing and proliferating visceral epithelial cells (podocytes). Antibodies against the urokinase-type plasminogen activator did not react with any elements of developing glomeruli; rather, they stained the proximal tubules in more mature parts of the kidney, as revealed by double immunostaining using antibodies against the brush border. The present results suggest that the tissue-type plasminogen activator plays a role in the differentiation of glomerular structures during nephron morphogenesis. PMID- 3114030 TI - PolyADP ribosylation and Friend erythroleukemic-cell differentiation: action of poly(ADP-ribose) polymerase inhibitors. AB - Previous studies have shown that benzamide and nicotinamide, two inhibitors of poly(ADP-ribose) polymerase, induce erythroid differentiation in Friend erythroleukemic cells. In contrast, we observed that two other commonly used inhibitors, i.e., 3-aminobenzamide and 3-methoxybenzamide, not merely failed to induce differentiation but actually inhibited it. Furthermore, we observed that benzamide at high concentrations induced differentiation, whereas at low concentrations, it inhibited differentiation. We propose that the induction occurring at high concentrations is due to the polar-planar properties of the molecule, while the inhibition at low concentrations might be due to the inhibition of poly(ADP-ribose) polymerase. Cells that were first exposed to an inducer (hexamethylene bisacetamide) and an inhibitor (3-aminobenzamide) and were subsequently incubated in medium lacking these substances did not differentiate. However, re-exposure to the inducer resulted in a very rapid increase in commitment to terminal differentiation. Therefore, 3-aminobenzamide appears to block differentiation prior to the commitment stage. We infer from these findings that polyADP-ribosylation is required for the terminal differentiation of Friend erythroleukemia cells. PMID- 3114031 TI - Anthracenedione antineoplastic agent effects on drug metabolism in vitro and in vivo: relationship between structure and mechanism of inhibition. AB - Two anthracenedione antineoplastic agents, mitoxantrone and the nonhydroxylated analog, ametantrone, were found to inhibit hepatic microsomal cytochrome P-450 dependent drug metabolism in vitro and in vivo. Ethoxycoumarin deethylase activity of phenobarbital-induced rabbit hepatic microsomes was inhibited 56 and 100% at 0.1 and 0.5 mM mitoxantrone, respectively, whereas activity was inhibited 38 and 88% at 0.1 and 0.5 mM ametantrone, respectively. Both mitoxantrone and ametantrone were noncompetitive inhibitors of ethoxycoumarin metabolism. Aryl hydrocarbon hydroxylase activity of hepatic microsomes was diminished 41 and 56% by 1 and 3 mM mitoxantrone, respectively; identical concentrations of ametantrone inhibited metabolism by 20 and 31%, respectively. In contrast to the inhibitory influence of both agents on monooxygenase activity, a differential effect on NADPH oxidation was observed. In the presence of benzo[alpha]-pyrene, mitoxantrone enhanced microsomal NADPH oxidation by 21%, whereas ametantrone produced a 22% decrease in cofactor oxidation relative to the control rate. The anthracenediones also inhibited hepatic cytochrome P-450-dependent monooxygenase activity in vivo, as evidenced by altered hexobarbital sleep times of mice. Mitoxantrone (20 and 40 mg/kg) prolonged sleep time by 59 and 68%, respectively; ametantrone (50 mg/kg) produced a 56% enhancement. These results demonstrate that both mitoxantrone and ametantrone inhibit drug metabolism in vitro and in vivo. PMID- 3114032 TI - Health and productivity of dairy cows fed polychlorinated biphenyls. AB - Holstein cows were studied through a complete lactation, a nonlactating period, and 42 days of a subsequent lactation for overt and subtle responses to a commercial mixture of polychlorinated biphenyls. Dosed cows (n = 4) received consecutive 60-day periods of daily dosing with 10, 100, and 1000 mg of Aroclor 1254. Control cows (n = 6) received daily sham doses. The following were recorded: daily milk production, feed intake, and health observations; weekly body weight, temperature, heart and respiratory rates and rectal palpation; semi monthly clinical chemistry determinations; and monthly milk fat, microbiological culture of quarter foremilk samples, and composite milk somatic cell counts. Mean daily milk production (22.4 +/- 1.1 vs 24.8 +/- 1.0 kg) and net energy of a complete lactation (1.46 +/- 0.05 vs 1.45 +/- 0.03 Mcal/kg dry matter intake) were not different (p = 0.85) for control and PCB-dosed cows. Milk production during the first 42 days of the subsequent lactation was also similar for control and dosed cows. Occurrences of injuries, dysfunctions, and general infections were not related to polychlorinated biphenyl exposure. Intramammary infections were detected for both lactations with 51 and 32 infections detected in microbiological cultures, respectively, for the control and dosed groups. Environmental pathogens were most frequently isolated from cases of clinically apparent mastitis. The majority of quarter infections detected were due to Corynebacterium bovis. Only one animal (dosed, necropsy revealed left oviduct obstructed) failed to conceive with three to six services required before conception for the other control and dosed cows. Exposure to polychlorinated biphenyls resulting in maximal residues in milk fat, near 100 micrograms/g, had no apparent effect on health and productivity. PMID- 3114033 TI - Arachidonic acid does not protect against sodium taurocholate damage to rat gastric epithelial cell cultures. AB - Arachidonic acid is cytoprotective against ethanol damage in vivo. Stimulation of production of endogenous prostaglandin has been postulated as a mechanism of this protection. The current study assessed the ability of arachidonic acid to protect gastric mucosal cells directly and the effect of arachidonic acid on prostaglandin production. To determine cytoprotection, sodium taurocholate was used as a damaging agent and cell viability was assayed by 51Cr release in vitro. By the dose response curve, 5 mM sodium taurocholate was chosen for the protective study. Cells were preincubated with arachidonic acid (0.1-10 micrograms/ml) and then incubated with 5 mM sodium taurocholate. The synthetic activity of prostaglandins by cultured cells was assessed using 14C arachidonic acid prelabeled cells. Media content of prostaglandin E2 was assayed by radioimmunoassay. Cell viability was assayed by 51Cr release. Our results showed that arachidonic acid did not significantly protect cultured gastric cells against sodium taurocholate damage, while larger doses of arachidonic acid produced cell damage. Furthermore, cultured gastric cells produced mainly prostaglandin E2 and prostaglandin I2 and arachidonic acid stimulated prostaglandin E2 production dose-dependently (p less than 0.01). In conclusion, arachidonic acid does not directly protect gastric mucosal cells in vitro. In vivo protection by arachidonic acid must be based on indirect factors such as preservation of microvasculature. PMID- 3114034 TI - Detection of the cholestatic factor in the liver tissue of patients with acute intrahepatic cholestasis. AB - A novel lymphokine, which we have designated as cholestatic factor (CF), was produced from peripheral blood lymphocytes of patients with drug-induced allergic intrahepatic cholestasis by stimulation with a causative drug in the presence of the liver soluble fraction containing liver-specific lipoprotein (LSP). Marked reductions in bile flow and bile acid excretion were induced in rats by injecting CF through a mesenteric vein. In order to confirm the presence of CF in the liver tissue of patients, we attempted to detect this lymphokine by using the enzyme labelled antibody method. As a result, CF was found in the liver tissue of eleven out of thirty-eight patients with acute intrahepatic cholestasis including one with hepatitis A type, one with hepatitis B type, two with hepatitis non-A non-B type, five with drug-induced allergic hepatitis, one with alcoholic hepatitis and one with lupoid hepatitis. In contrast, CF was undetectable in the liver tissue of patients without intrahepatic cholestasis. These results may additionally support our assumption that CF plays an important role in the induction of intrahepatic cholestasis in various liver diseases. PMID- 3114035 TI - Proliferation and immunoglobulin synthesis of peripheral blood mononuclear cells from patients with chronic liver disease stimulated by Staphylococcus aureus Cowan 1 and interleukin 2. AB - Proliferation and IgG synthesis of peripheral blood mononuclear cells (PBMC) in response to stimulation with recombinant interleukin 2 (IL-2) and Staphylococcus aureus Cowan 1 (SAC) were evaluated in 32 patients with chronic persistent hepatitis (CPH), chronic active hepatitis (CAH) and liver cirrhosis (LC). Eleven patients had serum HBe antigen, 10 presented with HBe antibody and 11 had non-A, non-B hepatitis. IgG synthesis of PBMC induced with the two stimuli was significantly decreased in patients with CAH and LC when compared with that of controls. However, the generated amounts of IgG were not associated with the HB virus carrier state. B cells and T4+ cells were responsible for the diminished IgG synthesis in patients with CAH and LC when assessed by coculture experiments. On the other hand, proliferative response of PBMC to IL-2 and SAC were similar in controls and patient groups. These findings indicate that IgG production level of PBMC stimulated with IL-2 and SAC can reflect the severity of the underlying disease in chronic hepatitis patients. PMID- 3114036 TI - Serum thyroid hormone levels in patients with fulminant hepatitis: usefulness of rT3 and the rT3/T3 ratio as prognostic indices. AB - To evaluate thyroid function in 19 patients with fulminant hepatitis (FH), we have measured total and free 3,5,3'-triiodothyronine (T3) and thyroxine (T4), 3,3',5'-triiodothyronine (reverse T3, rT3), thyroid-stimulating hormone (TSH) and thyroxin-binding globulin (TBG) in patients with FH, compared with those of 80 patients with other various liver diseases and of 10 healthy controls. Patients with FH showed the lowest values of serum T3 and the highest levels of rT3 among all patients with liver diseases studied. Furthermore, patients with FH showed a significant increase of rT3 in comparison with subacute hepatitis (SAH), "acute on-chronic" (AOC) type of hepatic failure, ordinary and severe forms of acute hepatitis (AHo and AHs) and decompensated liver cirrhosis (LC-D). In addition, serum T3 and rT3 and the rT3/T3 ratio significantly correlated with prothrombin time (PT) and plasma methionine level. We also found that serum T3 and rT3 concentrations and the rT3/T3 ratio showed early and rapid normalization in cases of FH that survived, but they did not improve in patients with fatal outcome. These results suggest that serum T3, particularly rT3 concentrations and the rT3/T3 ratio may be useful indicators for assessing the severity and prognosis of patients with FH and can be considered to the sensitive indices for functioning hepatic microsomal reserve as well. PMID- 3114038 TI - Impact of endoscopy on mortality from occult cancer in radiographically benign gastric ulcers. A probability analysis model. AB - Endoscopy is commonly used in the management of patients with radiographically benign gastric ulcers to detect occult malignancy. Clinical studies examining the cost-effectiveness of using endoscopy in such patients, however, have not been done. To address this issue using probability analysis, a probability tree was designed incorporating the possible clinical courses of patients with radiographically benign gastric ulcers managed with and without endoscopy, and probability estimates for each course were derived by compiling data from the literature. Probability and sensitivity analysis was used to compare the impact on overall mortality rate and cost-effectiveness of six commonly practiced methods of using endoscopy to manage patients with radiographically benign gastric ulcers: (1) all follow-up by upper gastrointestinal x-ray only; (2) endoscopy for nonhealing ulcers only; (3) endoscopy for all ulcers before medical therapy with all follow-up by upper gastrointestinal x-ray; (4) endoscopy for all ulcers after an initial trial of medical therapy; (5) endoscopy for all ulcers before therapy and for nonhealers; (6) endoscopy before therapy, and all follow up by endoscopy. This analysis predicts that the greatest decrease in mortality rate occurs when endoscopy is used before medical therapy and for all follow-up, reducing the estimated number of deaths per 1000 patients with radiographically benign gastric ulcers from 36.7 with follow-up by upper gastrointestinal x-ray only to 27.2. However, initial endoscopy with all subsequent follow-up by upper gastrointestinal x-ray increased the overall death rate by only a small amount, to 28.0, and was consistently the most cost-effective method, requiring 116 endoscopies and approximately 60,000 diagnostic dollars per additional 5-yr survivor. PMID- 3114037 TI - Gastrointestinal ulcer formation in rabbits immunized with prostaglandin E2. AB - Circulating prostaglandin E2 antibodies were produced in 12 rabbits immunized with prostaglandin E2-thyroglobulin conjugate and ulcers occurred in 10, usually in the stomach and less often in the small intestine. Immunization of rabbits with both prostaglandin E2 and 6-keto prostaglandin F1 alpha significantly increased the number of gastric ulcers compared with rabbits immunized with prostaglandin E2 alone. Gastrointestinal ulceration in prostaglandin E2-immunized rabbits was not prevented by oral enprostil. Gastrointestinal ulcers occurred as early as 6 wk after beginning immunization and often perforated with resulting fatality. Neither prostaglandin E2 antibodies nor ulcers developed in rabbits immunized with thyroglobulin vehicle (controls). Passive immunization of unimmunized rabbits with prostaglandin E2-hyperimmune plasma led to acute gastric ulcers within 9 days, whereas passive transfer of nonimmune plasma did not produce ulcers. This latter finding suggests that prostaglandin E2 antibodies per se were responsible for ulcer formation. PMID- 3114039 TI - [Two cases of homicide from the pre-ceramic neolithic era of Arabia Petraea]. AB - Human remains from Basta 1 (P PN B, 6. Mill. B.C.) and Sabra 1 (Khiamian, 7. Mill. B.C.) were prepared and studied; the results show that Basta 1 was a permanent settlement and Sabra 1 was a temporary summer camp. Both settlements are located in Arabia Petraea. Basta 1, No. 3477: The calvarium of a boy, aged 8 to 9 a, from Basta 1 was studied. The race can be determined as orientalide, according v. Eickstedt's classification. The boy was killed; as evidence by 2 blows to the skull occurring while he was alive. The cause of death has been reconstructed, using parallels taken from ethnological and forensic medical research. First, the boy received a light blow on the left forehead, with a sharp weapon. The authors present as a working hypothesis that the motivation for the death was rape, taking place as the boy was (probably) in a semi-conscious state. After recovering and rising to his feet, the boy suffered a deadly blow on the back of the skull (rabbit punch). A blunt instrument was used for the second blow. The body lay where it fell over 1 a or more; afterwards it was found by members of his own group. They removed the calvarium and buried it in their permanent settlement. The manner in which burial took place, would seem to indicate, that no further religious or ritual ceremony was involved. This type of crime has been observed e.g. as occurring among purely male groups-such as temporary herdsmen. In case of the boy from Basta 1, this would the earliest evidence for the occurrence of this type of sexual delinquency in prehistoric times. Sabra 1, No. 4088: Skull fragments of 2 individuals were recovered from a camp fire shifted by humans, in Sabra 1. Individual I is a male, aged 25 to 30 a; Individual II is a female of 25 to 30 a (or perhaps even younger). The examination showed that the bone fragments had been subjected to temperatures less than or equal to 200 degrees C (examination of bone material) and around 100 degrees C (evidence of charcoal material), when they were still fresh. The bones were not burned but grilled (or roasted). The evidence would indicate a case of antropophagy. The parallels in ethnological studies show that anthropophagy occurs only in farming societies, as religious rites; up to now, there is no evidence for this type of rites among the hunting and collecting groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3114040 TI - [Crystal chemical and micromorphologic evaluation of ancient bone discoveries (Arabia Petraea, Jordan) from the 10th millennium B.C]. AB - As specialisations of osteoarchaeometry become increasingly developed, so the need of new analytical techniques and tests of a skillful applicability becomes more necessary. The crystal-chemical and micromorphological evaluations of preserved bone discoveries implicate reliable methods as X-ray diffraction, electron microscopy, and spectroscopy with the skeletal materials and the soil environment in which bones are found. The reactivity of soils varies widely as geological and sedimentological conditions offer typical but different environments: gravels, chalk soil, clay, salt soils, sands, cave earths are examples of this wide variety, including atmospheric and biogenetic implications. The last mentioned features are strongly effective also in aride regions, with the well known fluctations of high parching and dewiness. However, despite the diversity in deposition and burial modes only few parameters govern the gradual decomposition of bone material: 1. pH value of the surrounding medium; 2. humidity of the surrounding medium, may be governed directly by autolysis; 3. transport of matter, related to grain size, pore volume, solubility behaviour; 4. physical pressure; 5. destruction by microorganisms; as well as the surrounding medium will be altered by the uptake and the transformation of the products of bone decomposition. The materials of investigation were skeletal fragments buried of ea. 10,000 a within the soft dune sediment of the western border mountains of Wadi el Araba (Arabia Petraea, Jordan). The discovered bones are, as a common feature of this locality Basta, strongly sintered--indication on the afore mentioned reactivity of the aride soil as well. Bone fragments were partially burnt at Sabra locality and discolored, and sintered also at these circumstances. The reactivity of the bone fragments is shown in terms of exchange reactions within the crystal structure of the bone mineral, apatite Ca5(PO4)3OH at the calcium sites, hydroxyl sites, and phosphate sites. These reaction schemes are interpreted in the details. This decomposition by substitution will often preserve the external appearance of buried bones. Fig. 1 and 2 show the extent of the actual ion exchange with the surrounding soil strata resp. transformed areas (sinter sheets); in the case of Basta material as a nearly total rearrangement of the anion lattice (phosphate, silicate vs. carbonate) as well as verified by Scanning-electron microscopy (Fig. 3, 4) and phase analyses by X-ray diffraction (Fig. 5-7): calcite and quartz are the principal components of the sinters, additional diffuse apatite lines appear in bone samples.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3114041 TI - [Gonadotropin stimulation and in vitro fertilization following selective hypophyseal suppression by LH/RH analogs]. AB - Out of 109 hMG stimulations for in vitro fertilization (IVF) 41 cycles (38%) had to be cancelled because of premature endogenous luteinization. Pretreatment with the LH/RH-agonist Buserelin induces selective pituitary suppression and prevents spontaneous LH-surge during hMG stimulation. The pharmacologic hypogonadotropism allows considerable flexibility with respect to the timing of starting gonadotropin stimulation and ovulation induction. In 74 Buserelin/hMG/IVF-cycles no premature luteinization occurred and all started stimulations yielded in follicular puncture. In addition increased oocyte recovery rate, significant higher fertilization rate and significant better pregnancy rate could be achieved as compared with hMG/IVF-cycles. In conclusion pharmacologic hypogonadotropism by administration of LH/RH-analogue reliably prevents endogenous luteinization and improves gonadotropin stimulation as well as IVF results. PMID- 3114043 TI - Increased gonadotropin levels in goldfish do not result in alterations in circulating thyroid hormone levels. AB - To determine whether increases in gonadotropin levels are capable of altering thyroid function in goldfish, plasma thyroid hormone levels were measured following induced changes in endogenous gonadotropin secretion and injection of carp gonadotropin. Radio-frequency lesions placed in the nucleus preopticus periventricularis or monosodium-L-glutamate-induced lesions of the posterior nucleus lateralis tuberis (NLT) of the hypothalamus were capable of stimulating significant increases in plasma gonadotropin levels, but were without effect on plasma triiodothyronine (T3) or thyroxine (T4) at time intervals ranging from 5 hr to 10 days. Likewise, injections of a superactive analog of gonadotropin releasing hormone resulted in profound increases in gonadotropin levels without associated changes in thyroid hormones. No changes in the circulating levels of T4 or T3 were observed in response to injection of purified carp gonadotropins whereas injection of bovine thyrotropin or carp pituitary extracts stimulated significant increases in T4. Radiofrequency lesions of the pituitary stalk or of the anterior NLT also resulted in significant increases in circulating levels of T4, but not of T3, at 10 and 30 hr postlesion. These results demonstrate that direct acute stimulation of circulating thyroid hormone levels is not an intrinsic action of endogenous goldfish gonadotropin and that activation of the reproductive system, leading to ovulation in some cases, is without effect on blood total thyroid hormone levels. Additionally, these results confirm that hypothalamic inhibition of the pituitary-thyroid axis exists in this teleost fish and demonstrate that interruption of this inhibition results in a time-dependent, high-magnitude increase in circulating thyroxine levels. PMID- 3114044 TI - Effects of thyrotropin-releasing hormone in vitro on thyrotropin and prolactin release from the turtle pituitary. AB - Effects of synthetic thyrotropin-releasing hormone (TRH) on thyrotropin (TSH) and prolactin (PRL) release by hemipituitaries of adult turtles, Chrysemys picta, were studied in an in vitro superfusion system. Significant increases in the rates of secretion of both immuno-reactive TSH and PRL occurred at doses between 0.01 and 10 ng/ml TRH. TSH secretion increased acutely by two-, to sixfold over nonstimulated secretion levels; responses tended to decline after many hours of continual stimulation, but output remained elevated above baseline in most cases. PRL secretion increased, parallel to TSH secretion during TRH stimulation. No significant difference was found in secretion rates between males and females, and no clear relationship between TRH responsiveness and reproductive stage was evident. These data provide the first direct evidence for the stimulation of TSH secretion by TRH in a reptile and confirm earlier reports that TRH stimulates the release of PRL in the turtle. Although previous in vivo studies indicated that TSH secretion was not affected by TRH in turtles, the present data indicate that the dose sensitivity of the chelonian gland is comparable with that of mammalian and avian pituitaries. Evidence for the role of TRH in endogenous TSH regulation is still lacking in reptiles but the present data provide evidence for functional TRH receptors on the chelonian thyrotrope and, hence, argue against the hypothesis that TSH stimulating activity of TRH evolved relatively recently in association with endothermy. PMID- 3114042 TI - Production of eicosanoids by the killifish gills and opercular epithelia and their effect on active transport of ions. AB - Gills and opercular epithelia of the killifish (Fundulus heteroclitus) homogenized and incubated with radiolabeled arachidonic acid were found to produce prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acids. These metabolites were identified using thin-layer chromatography, autoradiography, reverse-phase high-performance liquid chromatography, and ultraviolet spectroscopy. Addition of glutathione and epinephrine to the incubation mixture caused a diminution in the production of most eicosanoids (cyclooxygenase and lipoxygenase products) whereas indomethacin decreased only the cyclooxygenase metabolites. The effects of eicosanoids on short-circuit and potential difference across opercular epithelia mounted in a Ussing-type chamber were examined. Prostaglandin E2 had an inhibitory effect on ion transport whereas the sulfidopeptide leukotrienes (LTC4, LTD4, and LTE4) had a stimulatory effect. These results indicate that gills and opercular epithelia have the capacity to synthesize eicosanoids and that some of these metabolites may play a role in the regulation of ion transport in the kill fish. PMID- 3114045 TI - Parallel pathways of potassium transport in the alga Hydrodictyon reticulatum. Effects of calcium. AB - Inflow of potassium ions into the alga Hydrodictyon reticulatum is reduced in the dark, the reduction being accompanied by a change in the selectivity pattern with respect to alkali metal ions, observed in competition experiments and evaluated by the gnostic analysis as described by Kovanic. This suggests that in the light a special mechanism of potassium uptake with a characteristic selectivity is switched on. This mechanism can be also suppressed by too high (2 mmol/l) or too low (EGTA) concentration of calcium ions in the medium. Since the same applies to the light-induced alkalinization of the algal surroundings it seems that the light-induced potassium uptake is related to the light-induced alkalinization, e.g., via exchange of external potassium cations for intracellular protons. PMID- 3114046 TI - The nucleotide sequence of the gene coding for Drosophila melanogaster yolk protein 3. AB - The entire sequence of the Drosophila melanogaster yolk protein 3 (YP3) gene (yp3), including 1822 nucleotides (nt) of 5'- and 834 nt of 3'-flanking DNA, has been determined. In addition, the 5' and 3' ends of the mRNA and the two introns have been mapped. The predicted amino acid sequence of YP3 has considerable homology (43%) to the other two yolk proteins of D. melanogaster. The nucleotide sequence of yp3 was compared to the other two yolk protein genes which have the same developmental pattern of expression. In addition to extensive homology between the protein coding regions, we found two small regions of homology between yp3 flanking sequences and a segment of DNA required for normal expression of the yolk protein 1 gene in adult female fat bodies. PMID- 3114047 TI - The immunoglobulin lambda locus in rat consists of two C lambda genes and a single V lambda gene. AB - The immunoglobin lambda locus of the rat has been studied. Germ-line V lambda and C lambda genes were isolated from recombinant-phage libraries and characterized by nucleotide sequencing. The results showed that the lambda locus of the rat contains one single V lambda gene and two C lambda genes, thus representing one of the least complex lambda loci so far characterized. The two C lambda genes are separated by a spacer approx. 3 kb long. Two J segments are located at the 5' side of each C lambda gene. One of the C lambda genes (C lambda 1) probably represents a pseudogene, as the J lambda 1 segments have non-functional recombination and splice signals. The organization of the rat lambda locus resembles that of mouse, except that only one cluster is present in the rat. Thus since the evolutionary separation of the rat and mouse species ten MYR ( = 10(6) years) ago, either one cluster has been lost from the rat, or duplicated in the mouse. PMID- 3114048 TI - Management of orthostatic hypotension in the elderly. AB - Orthostatic hypotension (OH) is a common problem in old age that can seriously affect the quality of life, leading to a progressive decline in health. In the elderly, the literature suggests that multiple causes predominate. This article proposes a stepped-care approach to the management of OH. A stepped-care therapy applied appropriately allows maximum benefit with the least number of drugs, thereby minimizing side effects. PMID- 3114049 TI - Private long-term care insurance: cost, coverage, and restrictions. PMID- 3114050 TI - The financial capacity of the elderly to insure for long-term care. PMID- 3114051 TI - Assessing the elderly's preferences for lifecare retirement options. PMID- 3114052 TI - [Dinitrophenol compounds: toxicology, therapy and prevention of poisoning (review of the literature)]. PMID- 3114053 TI - Melatonin: its antagonism of thyroxine's antisomatotrophic activity in male Syrian hamsters. AB - The effects of daily evening melatonin injections on serum and pituitary levels of growth hormone (GH) and follicle stimulating hormone (FSH) were investigated in male Syrian hamsters receiving thiourea in the drinking water. Melatonin injections, by themselves, had no significant effect on serum or pituitary GH. Thiourea induced hypothyroidism reduced pituitary GH content but increased serum GH several fold. Daily thyroxin (T4) injections for 3 weeks partially restored pituitary GH content and reduced circulating GH to control values. Melatonin injections prevented T4 from reducing circulating GH levels to normal in hamsters receiving thiourea. As previously reported, FSH levels in serum and pituitary were reduced by melatonin. Thiourea-induced hypothyroidism prevented this effect. Daily T4 injections increased circulating FSH levels above control levels; melatonin injections prevented this increase in serum FSH. These observations show that melatonin and T4 have antagonistic actions on GH and FSH release from the pituitary. We conclude that melatonin influences the release of hypothalamic hormones regulating GH and FSH release from the pituitary. The effects of T4 on the sensitivity to melatonin injections could be accounted for by thyroid hormone regulation of pituitary receptors for hypothalamic hormones. An alternative explanation is that T4 regulates the concentration of melatonin receptors in the central nervous system. PMID- 3114054 TI - Effect of beta-amino-propionitrile on the regenerating newt limb evaluated by uptake of 3H-proline and 3H-lysine. AB - Newt forelimbs were unilaterally amputated and Beta-amino propionitrile (BAPN) was added to the water in which the newts were maintained. Sixty-three days after amputation, animals were injected with either 3H-proline or 3H-lysine. Forelimbs distal to the elbow of both amputated and non-amputated sides were removed 72 hours later. Uptake of 3H-proline and 3H-lysine in whole limbs was assessed by liquid scintillation and in cartilage cells and matrix by autoradiography. Amputation was a potent stimulus to both collagen formation and maturation during regeneration. BAPN reduced the stimulatory effect of amputation on collagen formation but not on its maturation. Collagen synthesis and maturation are independent events and, in intact non-regenerating limbs, BAPN adversely affected collagen maturation while collagen synthesis was unaltered. PMID- 3114055 TI - [Feasibility of studying regional gas exchange in children with chronic bronchopulmonary pathology using the mass spectrometry method]. PMID- 3114057 TI - Concurrent radiation and chemotherapy for carcinoma of the cervix recurrent after radical surgery. AB - Results of salvage therapy in patients with carcinoma of the cervix, recurrent after primary surgery, have been dismal even when disease was apparently confined to the pelvis. Further surgery or radiation therapy cured only some with central pelvic disease alone who had recurred at intervals longer than 6 months after primary therapy. To try to improve the results of salvage therapy, we used a combination of concurrent chemotherapy, 5-Fluorouracil with or without Mitomycin C, and radiation therapy. Seventeen patients were treated. Recurrent disease was present in the pelvis or pelvis and paraaortic nodes after radical surgery for Stage IB carcinoma of the cervix. Eight of seventeen (47%) are alive, disease free, 21 to 58 months after therapy. Seven of the eight had biopsy proven recurrence. Five of eight had recurred within 9 months of primary surgery and 7/8 had a component of pelvic side wall disease. Thus the survivors had unfavorable prognostic features. Nevertheless, the use of concurrent radiation and chemotherapy produced an exceptionally high proportion of sustained complete remissions and possible cures. PMID- 3114056 TI - Jejunal water and electrolyte absorption from two proprietary enteral feeds in man: importance of sodium content. AB - Jejunostomy losses of Na+ and water during enteral nutrition after massive intestinal resection may be severe. We have attempted to analyse this practical problem by using an in vivo perfusion technique in healthy volunteers to study Na+, water and nutrient absorption from a short (25 cm) segment of jejunum during perfusion of an isotonic solution of the elemental diet Vivonex. Further solutions made from the amino acid and carbohydrate components of Vivonex were also perfused in part I of the study in order to determine the causes of the marked Na+ and water secretion seen during Vivonex perfusion. Low initial Na+ concentration was found to be the major determinant of net Na+ secretion, initial Na+ concentration correlating significantly with Na+ absorption (r = 0.95, n = 7 p less than 0.001). Water absorption correlated with net absorption of NaCl (r = 0.82, n = 7 p less than 0.01). There was, however, a better correlation with total absorption of NaCl plus amino acids (r = 0.99, n = 7, p less than 0.01). In part II of the study separate isotonic solutions of NaCl, glucose, and the polymeric diet, Ensure were also studied. Net sodium secretion occurred during glucose and Ensure perfusion, as predicted from their low Na+ concentration. Owing to rapid sucrose absorption from Ensure there was substantial luminal disappearance of osmotically active particles and hence marked water absorption, which was accurately predicted using the regression equation for water absorption derived in part I, substituting sucrose absorption for amino acid absorption. We conclude that the marked Na+ and water secretion observed during Vivonex perfusion is not a unique property of this amino acid based diet but is due to its low Na+ content. PMID- 3114058 TI - Prevention of infection in patients with acute nonlymphocytic leukemia by several drug treatment regimens. PMID- 3114059 TI - Modification of tRNA and its applicability for the assessment of prognosis, state of differentiation, and clonality in human leukemias and lymphomas. PMID- 3114060 TI - Expression of CD-15 antigen on leukemic cells--a new prognostic factor for ability to achieve complete remission and for survival in ANLL. PMID- 3114061 TI - Treatment of standard- and high-risk childhood acute lymphoblastic leukaemia with two CNS prophylaxis regimens. PMID- 3114062 TI - [Intravaginal lyophilized Lactobacilli in the therapy of nonspecific fluor vaginalis]. PMID- 3114064 TI - Is there a correct time to begin treatment of multiple myeloma? PMID- 3114063 TI - Lysine-vasopressin does not affect basal and LH-RH-stimulated LH and FSH release during the menstrual cycle of normal women. AB - In order to test possible effects of lysine-vasopressin (LVP) on basal and LH-RH stimulated LH and FSH release, an intravenous bolus of LVP (0.06 IU/kg body weight) was injected alone or 10 min before LH-RH (100 micrograms i.v.) in 33 normal women in the follicular, periovulatory and luteal phase of their menstrual cycle. The administration of LVP modified neither the basal secretion of the gonadotropins nor the LH-RH-induced LH and FSH release. These data suggest that in humans, vasopressin is not involved in the control of gonadotropin release at the level of the anterior pituitary. PMID- 3114065 TI - Chromosome patterns of relapses following allogeneic bone marrow transplantation for acute non-lymphocytic leukemia. Description of three cases. PMID- 3114068 TI - Primary lymphoma of the central nervous system. A clinical and immunohistological study of 8 patients. PMID- 3114067 TI - Effects of lithium on human leukocyte chemotaxis. Indirect evidence from the use of potassium and vinblastine concerning the modulation of microtubular system. PMID- 3114066 TI - In vivo administration of bromodeoxyuridine and flow cytometry for cell kinetic studies in human malignancies. PMID- 3114069 TI - Bone marrow histology in patients with hairy cell leukemia (HCL) treated by human lymphoblastoid interferon. PMID- 3114070 TI - Acute promyelocytic leukemia: clinical aspects and results of treatment in 62 patients. PMID- 3114071 TI - Trimethoprim/sulfamethoxazole plus ketoconazole prophylaxis in acute leukemia. PMID- 3114072 TI - Visceral leishmaniasis presenting as dyserythropoiesis associated with increased i-antigenicity of erythrocytes. PMID- 3114073 TI - A case of parotideal myeloma in Sjogren's syndrome. PMID- 3114074 TI - Multiple myeloma: biological and clinical significance of bone marrow plasma cell labelling index. PMID- 3114075 TI - In vitro purging of leukemia and solid tumor cells by merocyanine 540. PMID- 3114076 TI - Pure red cell aplasia. Transient remission in connection with acute hepatitis. PMID- 3114077 TI - LDH isoenzymes in blast crisis of chronic granulocytic leukemia. PMID- 3114078 TI - Acute leukaemia following cisplatin for ovarian cancer. PMID- 3114079 TI - Ketoconazole for prevention of fungal infections in neutropenic leukemia patients. PMID- 3114080 TI - Association of AIDS and B-cell lymphomas in two drug addicted men. PMID- 3114081 TI - Management of non-Hodgkin's lymphomas in the elderly. PMID- 3114082 TI - Recurrent intracranial hemorrhage in an infant with congenital factor VII deficiency. PMID- 3114083 TI - Recurrent Salmonella typhimurium bacteremia in a hemophiliac B patient with ARC: prognostic index of evolution toward AIDS. PMID- 3114084 TI - Evaluation of erythroid marrow function in anemic patients. PMID- 3114085 TI - Lymphocyte proliferative enhancing or inhibiting factors released by four human myeloid cell lines. PMID- 3114086 TI - In vitro effects of adenosine induced supernatants on human T lymphocyte functions. PMID- 3114087 TI - Surface immunoglobulin intensivity and p67 (CD5) antigen expression define different forms of B-cell chronic lymphocytic leukaemia. PMID- 3114088 TI - Immunophenotypic characterization and classification of T-acute lymphoblastic leukemia. Report of 30 cases. PMID- 3114089 TI - Characterization of anti-streptolysin O activity of a human monoclonal IgG lambda. PMID- 3114090 TI - Re-evaluation of prognosis in stages I and II Hodgkin's disease with bulky mediastinal involvement. PMID- 3114091 TI - G-6-PD Cagliari II: a new G-6-PD variant. PMID- 3114092 TI - Evans syndrome: a case of autoimmune thrombocytopenia and autoimmune hemolytic anemia caused by anti-Jka. PMID- 3114093 TI - Cell lineage switches in blast crisis of a Ph1 positive chronic granulocytic leukemia. PMID- 3114094 TI - Simultaneous occurrence of chronic granulocytic leukemia and chronic lymphoid leukemia. PMID- 3114095 TI - Lupus anticoagulant and coeliac disease: a case report. PMID- 3114096 TI - Surface mechanisms of platelet adhesion and aggregation. PMID- 3114097 TI - The preparation for splenectomy of adult patients with chronic idiopathic thrombocytopenic purpura by intravenous administration of monomeric intact immunoglobulin. PMID- 3114098 TI - 6-Thioguanine treatment for polycythemia vera and essential thrombocythemia. PMID- 3114100 TI - A new automated method for kallikrein-prekallikrein determination. PMID- 3114099 TI - Recombinant alpha-2a interferon (alpha-IFN) in the treatment of essential thrombocythaemia. Preliminary report. PMID- 3114101 TI - Measurement of factor VIII procoagulant antigen in normal subjects and in hemophilia A patients by an immunoradiometric assay and by an enzyme-linked immunosorbent assay. AB - Factor VIII coagulant antigen (FVIII:Ag) and FVIII coagulant activity (FVIII:C) were measured in 102 healthy individuals, in 5 hemophilia A carriers and in 21 hemophilia A patients before and after infusion of heat-treated high-purity FVIII concentrates. Factor VIII:Ag was determined by a solid-phase micro enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies and by a conventional solid-phase immunoradiometric assay (IRMA). Factor VIII:C was assessed using a one-stage assay. The micro ELISA was decidedly more precise than the IRMA. There was a close correlation between the results obtained by the three assays in the plasma of healthy subjects and in hemophilia A carriers. After transfusion of FVIII concentrates to hemophilia A patients, the FVIII:Ag recoveries were significantly lower than the FVIII:C recoveries and the biological half-life of FVIII:Ag was significantly shorter than for FVIII:C. The calculated half-life of FVIII:C was longer than in any previous study. PMID- 3114102 TI - Effect of oral anticoagulant treatment on plasma and serum antithrombin III: a study on 172 patients at different levels of anticoagulation. AB - Antithrombin III (AT III) functional levels are much lower in serum than in plasma; during oral anticoagulation this difference is reduced. Plasma and serum of 172 patients taking vitamin K antagonists were tested for AT III antigen and both AT III heparin cofactor and anti-Xa heparin cofactor. Crossed immunoelectrophoresis of AT III on heparin-agarose was also carried out in plasma and serum. The patients were divided into four groups: (1) international normalized ratio (INR) 9.3-4.1, n = 25; (2) INR 4.0-2.5, n = 73; (3) INR 2.4-2.0, n = 40, and (4) INR 1.9-1.5, n = 34. 66 healthy subjects were used as controls. Plasma levels of AT III antigen, AT III heparin cofactor, and anti-Xa heparin cofactor were the same in all groups. In all groups all serum AT III parameters were higher than in controls; crossed immunoelectrophoresis of AT III on heparin agarose indicated that this finding was due to a lower formation of complexed AT III in serum. AT III heparin cofactor serum values were the same whatever the INR over a large range (9.3-1.5); the highest anti-Xa heparin cofactor serum levels were noted in the groups treated more intensely (groups 1 and 2). PMID- 3114104 TI - [Assessing severity of disease in a pediatric intensive care unit]. PMID- 3114103 TI - Protamine-induced platelet aggregation and clotting investigated by ultrasound. AB - Using high-resolution real-time ultrasound to monitor platelet aggregation and plasma clotting, the effect of protamine on platelets was evaluated in a dynamic system of plasma in vitro. Protamine induced platelet aggregation preceding plasma clotting at both low (1.6 s-1) and moderate (22.6 s-1) shear rates. The onset of aggregation and clotting was accelerated at the higher shear rate. Low shear clots were heterogeneous on ultrasonic imaging, whereas moderate-shear clots were more densely homogeneous. Protamine-induced platelet aggregation was reversed by additional heparin. Pretreatment of plasma with prostacyclin prevented protamine-induced aggregation, but clot formation occurred. However, such clots were less echogenic. EGTA and hirudin inhibited both aggregation and clotting. Our ultrasonic aggregometry showed that platelet aggregation was induced by protamine before clots formed, and that not only shear rate but platelet activation might affect the rate and composition of plasma clots. PMID- 3114105 TI - Metabolic and physiological consequences of the effect of phenylhydrazonopropanedinitriles on Candida albicans. AB - Phenylhydrazonopropanedinitrile, a model uncoupler of oxidative phosphorylation, was used in studies of metabolic and physiological consequences of uncoupling at the cellular level in Candida albicans. Concentrations stimulating respiration induce a faster glucose consumption at a practically unchanged respiratory coefficient. The extracellular production of acids is also without significant changes. When applying higher concentrations of the uncoupler respiration was inhibited, similarly to glucose consumption and acid production. This fact is due to nonspecific interactions of the alkylation type with mercapto groups of functional proteins. Phenylhydrazonopropanedinitrile influences energy-generating processes resulting in slowing down or interruption of biosynthetic processes and occasionally even growth of Candida albicans. PMID- 3114107 TI - [Diagnosis and follow-up of osteomyelitis of the jaw using 4-phase and labeled leukocyte scintigraphy]. PMID- 3114106 TI - The effects of dietary cabbage on xenobiotic-metabolizing enzymes and the binding of aflatoxin B1 to hepatic DNA in rats. AB - The effect of dietary cabbage (Brassica oleracea) on the binding of aflatoxin B1 (AFB1) to hepatic DNA and on the activities of liver and intestinal microsomal and cytosolic enzymes was studied in weanling male Fischer 344 rats. Freeze-dried cabbage was fed to rats at a level of 25% in the diet for 21 days, while others received a basal diet. In the cabbage-fed group there was an 87% (P less than 0.01) reduction in the binding of AFB1 to hepatic DNA 2 hr after the ip injection of [3H]AFB1 (3 micrograms/kg). There was also a 41% (P less than 0.05) increase in liver weight expressed relative to body weight. Hepatic and intestinal glutathione S-transferase activities were significantly increased (2.1- and 2.3 fold, respectively) over those in rats fed the basal diet. Hepatic and intestinal microsomal epoxide hydrolase activities were significantly increased (2.6- and 1.4-fold, respectively) over the basal group. Intestinal aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin O-deethylase (ECD) activities were significantly increased (2.3- and 2.5-fold, respectively), over the basal group but dietary cabbage had no significant effect on hepatic AHH or ECD activities. PMID- 3114108 TI - [Place and significance of leukocyte scintigraphy of osteomyelitic processes in the jaw region]. PMID- 3114109 TI - Questioning the adequacy of long-term care IRAs. PMID- 3114110 TI - Health giving patterns of philanthropic foundations. PMID- 3114111 TI - Physicians' ethics: keeping sight of the ideal.